bluuebunny/crossref_metadata_2025 huggingface dataset:
DR5‐Cbl‐b/c‐Cbl‐TRAF2 complex inhibits TRAIL‐induced apoptosis by promoting TRAF2‐mediated polyubiquitination of caspase‐8 in gastric cancer cells
Authors: Xu Ling , Zhang Ye , Qu Xiujuan , Che Xiaofang , Guo Tianshu , Li Ce , Ma Rui , Fan Yibo , Ma Yanju , Hou Kezuo , Li Danni , Hu Xuejun , Liu Bofang , Yu Ruoxi , Yan Hongfei , Gong Jing , Liu Yunpeng
Published: October 2017

Ubiquitination of caspase‐8 regulates TNF‐related apoptosis‐inducing ligand (TRAIL) sensitivity in cancer cells, and the preligand assembly complex plays a role in caspase‐8 polyubiquitination. However, whether such a complex exists in gastric cancer cells and its role in TRAIL‐triggered apoptosis is unclear. In this study, DR5, casitas B‐lineage lymphoma‐b (Cbl‐b)/c‐Cbl, and TRAF2 formed a complex in TRAIL‐resistant gastric cancer cells, and Cbl‐b and c‐Cbl were the critical adaptors linking DR5 and TRAF2. Treatment with TRAIL induced caspase‐8 translocation into the DR5‐Cbl‐b/c‐Cbl‐TRAF2 complex to interact with TRAF2, which then mediated the K48‐linked polyubiquitination of caspase‐8. The proteasome inhibitor bortezomib markedly enriched the p43/41 products of caspase‐8 activated by TRAIL, indicating proteasomal degradation of caspase‐8. Moreover, TRAF2 knockdown prevented the polyubiquitination of caspase‐8 and thus increased TRAIL sensitivity. In addition, the inhibition of Cbl‐b or c‐Cbl expression and overexpression of miR‐141 targeting Cbl‐b and c‐Cbl partially reversed TRAIL resistance by inhibiting the interaction between TRAF2 and caspase‐8 and the subsequent polyubiquitination of caspase‐8. These results indicate that the DR5‐Cbl‐b/c‐Cbl‐TRAF2 complex inhibited TRAIL‐induced apoptosis by promoting TRAF2‐mediated polyubiquitination of caspase‐8 in gastric cancer cells.
Three‐Dimensional Seismic Imaging of Ancient Submarine Lava Flows: An Example From the Southern Australian Margin
Authors: Reynolds P. , Holford S. , Schofield N. , Ross A.
Published: October 2017

Submarine lava flows are the most common surficial igneous rock on the Earth. However, they are inherently more difficult to study than their subaerial counterparts due to their inaccessibility. In this study, we use newly acquired 3‐D (three‐dimensional) seismic reflection data to document the distribution and morphology of 26 ancient, buried lava flows within the middle Eocene‐aged Bight Basin Igneous Complex, offshore southern Australia. Many of these lava flows are associated with volcanoes that vary from 60 to 625 m in height and 0.3 to 10 km in diameter. Well data and seismic‐stratigraphic relationships suggest that the lava flows and volcanoes were emplaced offshore in water depths of <300 m. The lava flows range from 0.5 to 34 km in length and 1 to 15 km in width and are typified by tabular and dendritic forms. This morphological variation may result from differing lava effusion rates and/or the volumes of lava erupted. We demonstrate that: (1) the dendritic flows contain complex lava distribution systems and kipukas, features never‐before observed from seismic data; and (2) the distribution and morphology of the lava flows was strongly controlled by the emplacement of magmatic intrusion‐induced forced folds. This suggests that magmatic intrusions may play an important role in controlling the distribution of lava flows elsewhere. Our study highlights the usefulness of seismic data in studying the manifestation of submarine volcanism, and provides quantitative data on the extent and distribution of an ancient submarine volcanic province along the southern Australian margin.
Effect of Snow Salinity on CryoSat‐2 Arctic First‐Year Sea Ice Freeboard Measurements
Authors: Nandan Vishnu , Geldsetzer Torsten , Yackel John , Mahmud Mallik , Scharien Randall , Howell Stephen , King Joshua , Ricker Robert , Else Brent
Published: October 2017

The European Space Agency's CryoSat‐2 satellite mission provides radar altimeter data that are used to derive estimates of sea ice thickness and volume. These data are crucial to understanding recent variability and changes in Arctic sea ice. Sea ice thickness retrievals at the CryoSat‐2 frequency require accurate measurements of sea ice freeboard, assumed to be attainable when the main radar scattering horizon is at the snow/sea ice interface. Using an extensive snow thermophysical property dataset from late winter conditions in the Canadian Arctic, we examine the role of saline snow on first‐year sea ice (FYI), with respect to its effect on the location of the main radar scattering horizon, its ability to decrease radar penetration depth, and its impact on FYI thickness estimates. Based on the dielectric properties of saline snow commonly found on FYI, we quantify the vertical shift in the main scattering horizon. This is found to be approximately 0.07 m. We propose a thickness‐dependent snow salinity correction factor for FYI freeboard estimates. This significantly reduces CryoSat‐2 FYI retrieval error. Relative error reductions of ~11% are found for an ice thickness of 0.95 m and ~25% for 0.7 m. Our method also helps to close the uncertainty gap between SMOS and CryoSat‐2 thin ice thickness retrievals. Our results indicate that snow salinity should be considered for FYI freeboard estimates.
Empirical Model of Precipitating Ion Oval
Authors: Goldstein Jerry
Published: October 2017

In this brief technical report published maps of ion integral flux are used to constrain an empirical model of the precipitating ion oval. The ion oval is modeled as a Gaussian function of ionospheric latitude that depends on local time and the Kp geomagnetic index. The three parameters defining this function are the centroid latitude, width, and amplitude. The local time dependences of these three parameters are approximated by Fourier series expansions whose coefficients are constrained by the published ion maps. The Kp dependence of each coefficient is modeled by a linear fit. Optimization of the number of terms in the expansion is achieved via minimization of the global standard deviation between the model and the published ion map at each Kp. The empirical model is valid near the peak flux of the auroral oval; inside its centroid region the model reproduces the published ion maps with standard deviations of less than 5% of the peak integral flux. On the subglobal scale, average local errors (measured as a fraction of the point‐to‐point integral flux) are below 30% in the centroid region. Outside its centroid region the model deviates significantly from the H89 integral flux maps. The model's performance is assessed by comparing it with both local and global data from a 17 April 2002 substorm event. The model can reproduce important features of the macroscale auroral region but none of its subglobal structure, and not immediately following a substorm.
Matrix metalloproteinase‐1 facilitates MSC migration via cleavage of IGF‐2/IGFBP2 complex
Authors: Guan Shou P. , Lam Alan T.L. , Newman Jennifer P. , Chua Kevin L.M. , Kok Catherine Y.L. , Chong Siao T. , Chua Melvin L.K. , Lam Paula Y.P.
Published: October 2017

The specific mechanism underlying the tumor tropism of human mesenchymal stem cells (MSCs) for cancer is not well defined. We previously showed that the migration potential of MSCs correlated with the expression and protease activity of matrix metalloproteinase (MMP)‐1. Furthermore, highly tumor‐tropic MSCs expressed higher levels of MMP‐1 and insulin‐like growth factor (IGF)‐2 than poorly migrating MSCs. In this study, we examined the functional roles of IGF‐2 and MMP‐1 in mediating the tumor tropism of MSCs. Exogenous addition of either recombinant IGF‐2 or MMP‐1 could stimulate MSC migration. The correlation between IGF‐2, MMP‐1 expression, and MSC migration suggests that MMP‐1 may play a role in regulating MSC migration via the IGF‐2 signaling cascade. High concentrations of IGF binding proteins (IGFBPs) can inhibit IGF‐stimulated functions by blocking its binding to its receptors and proteolysis of IGFBP is an important mechanism for the regulation of IGF signaling. We thus hypothesized that MMP‐1 acts as an IGFBP2 proteinase, resulting in the cleavage of IGF‐2/IGFBP2 complex and extracellular release of free IGF‐2. Indeed, our results showed that conditioned media from highly migrating MSCs, which expressed high levels of MMP‐1, cleaved the IGF‐2/IGFBP2 complex. Taken together, these results showed that the MMP‐1 secreted by highly tumor‐tropic MSCs cleaved IGF‐2/IGFBP2 complex. Free IGF‐2 released from the complex may facilitate MSC migration toward tumor.
General and Abdominal Obesity as Risk Factors for Late‐Life Mobility Limitation After Total Knee or Hip Replacement for Osteoarthritis Among Women
Authors: Shadyab Aladdin H. , Li Wenjun , Eaton Charles B. , LaCroix Andrea Z.
Published: October 2017

Objective

To investigate associations of body mass index (BMI), waist circumference (WC), and waist/hip ratio (WHR) with survival to age 85 years with mobility limitation or death before age 85 years among older women with total knee replacement (TKR) or total hip replacement (THR) for osteoarthritis (OA).

Methods

This was a prospective study of women (ages 65–79 years at baseline) from the Women's Health Initiative, recruited during 1993–1998 and followed through 2012. Women's Health Initiative data were linked to Medicare claims data to determine TKR (n = 1,867) and THR (n = 944) for OA. Women were followed for up to 18 years after undergoing THR or TKR to determine mobility status at age 85 years.

Results

Compared with normal‐weight women, overweight, obese I, and obese II women with THR had significantly increased risk of survival to age 85 years with mobility limitation (P < 0.001 for linear trend), with the strongest risk among obese II women (odds ratio [OR] 4.37 [95% confidence interval (95% CI) 1.96–9.74]). Obese II women with THR also had increased risk of death before age 85 years. Women with THR and WC >88 cm relative to ≤88 cm had increased risk of survival to age 85 years with mobility limitation (OR 1.65 [95% CI 1.17–2.33]) but not death before age 85 years. High BMI, WC, and WHR were associated with significantly increased risk of late‐life mobility limitation and death among women with TKR for OA.

Conclusion

Among older women who underwent THR or TKR for OA, baseline general and abdominal obesity were associated with increased risk of late‐life mobility limitation.
Generalized maximum correntropy detector for non‐Gaussian environments
Authors: Hakimi Saeed , Abed Hodtani Ghosheh
Published: October 2017

This paper addresses the problem of multiple‐hypothesis detection. In many applications, assuming the Gaussian distribution for undesirable disturbances does not yield a sufficient model. On the other hand, under the non‐Gaussian noise/interference assumption, the optimal detector will be impractically complex. Therewith, inspired by the optimal maximum likelihood detector, a suboptimal detector is designed. In particular, a novel detector based on the generalized correntropy, which adopts the generalized Gaussian density function as the kernel, is proposed. Simulations demonstrate that, in non‐Gaussian noise models, the generalized correntropy detector significantly outperforms other commonly used detectors. The efficient and robust performance of the proposed detection method is illustrated in both light‐tailed and heavy‐tailed noise distributions.
Protein Biophosphors: Biodegradable, Multifunctional, Protein‐Based Hydrogel for White Emission, Sensing, and pH Detection
Authors: Benson Kyle , Ghimire Ananta , Pattammattel Ajith , Kumar Challa V.
Published: October 2017

A highly efficient, multifunctional, bioderived white‐emitting hydrogel (biophosphor) consisting of crosslinked bovine serum albumin and three fluorescent dyes, Coumarin 460, fluorescein, and 5(6)‐carboxy‐x‐rhodamine, is reported here. White emission is obtained upon excitation of the biophosphor at 365 nm with appropriate mole ratios of the above dyes. The CIE 1931 chromaticity coordinates of white emission with 365 nm excitation are (0.36, 0.37), and the correlated color temperature is 5300 K. Multifunctional nature of the biophosphor is also demonstrated. A UV‐light‐emitting‐diode (361 nm) coated with this biophosphor, for example, indicates white emission (CIE 0.28, 0.31) with a half‐life of 106 (±5) h. The white emission is also highly sensitive to pH over a broad range (pH 1–11). Incorporation of glucose oxidase and peroxidase in the biophosphor allows for the detection of glucose over a physiologically relevant range of 1.8–288 mg dL−1. This is a unique, advanced biophosphor with LED and sensing applications, and it is the first example of a multifunctional, proteinaceous white emitter.
A pseudo‐transient optimization framework for periodic processes: Pressure swing adsorption and simulated moving bed chromatography
Authors: Tsay Calvin , Pattison Richard C. , Baldea Michael
Published: October 2017

Periodic systems are widely used in separation processes and in reaction engineering. They are designed for and operated at a cyclic steady state (CSS). Identifying and optimizing the CSS has proven to be computationally challenging. A novel framework for equation‐oriented simulation and optimization of cyclic processes is introduced. A two‐step reformulation of the process model is proposed, comprising, (1) a full discretization of the time and spatial domains and (2) recasting the discretized model as a differential‐algebraic equation system, for which theoretical stability guarantees are provided. Additionally, a mathematical, structural connection between the CSS constraints and material recycling is established, which allows us to deal with these conditions via a “tearing” procedure. These developments are integrated in a pseudo‐transient design optimization framework and two extensive case studies are presented: a simulated moving bed chromatography system and a pressure swing adsorption process. © 2017 American Institute of Chemical Engineers AIChE J, 64: 2982–2996, 2018
Current paradigms in the management of Philadelphia chromosome positive acute lymphoblastic leukemia in adults
Authors: El Fakih Riad , Jabbour Elias , Ravandi Farhad , Hassanein Mona , Anjum Farhan , Ahmed Syed , Kantarjian Hagop
Published: October 2017

Philadelphia chromosome‐positive (Ph‐positive) acute lymphoblastic leukemia (ALL) is a biologically, clinically, and genetically distinct subtype of precursor‐B ALL. The Ph chromosome, results from a reciprocal translocation of the ABL1 kinase gene on chromosome 9 to the breakpoint cluster region (BCR) gene on chromosome 22. Depending on the translocation breakpoint, typically a p210 BCR‐ABL1 or a p190 BCR‐ABL onc protein are generated; both are constitutively active tyrosine kinases that play a central role to alter signaling pathways of cell proliferation, survival, and self‐renewal, leading to leukemogenesis. In Ph‐positive ALL, the p190‐BCR‐ABL (minor [m]‐bcr) subtype is more frequent than the p210‐BCR‐ABL (major [M]‐bcr) subtype, commonly found in chronic myeloid leukemia. The Philadelphia chromosome is the most frequent recurrent cytogenetic abnormality in elderly patients with ALL. Its incidence increases with age, reaching ∼50% in patients with ALL aged 60 years and over. Patients traditionally had a very poor outcome with chemotherapy, particularly if they do not undergo allogeneic hematopoietic cell transplantation (allo‐HCT) in first complete remission (CR1). With the availability of multiple tyrosine kinase inhibitors (TKI), the therapeutic armamentarium is expanding quickly. However, there is no consensus on how to best treat Ph‐positive ALL. With modern therapy, improved outcomes have led to the emergence of a number of controversies, including the need for intensive chemotherapy, the ideal TKI, and whether all eligible patients should receive an allo‐HSCT, and if so, what type. Here, we discuss these controversies in light of the available literature.
Relatively favorable outcome after allogeneic stem cell transplantation for BCR‐ABL1‐positive AML: A survey from the acute leukemia working party of the European Society for blood and marrow transplantation (EBMT)
Authors: Lazarevic Vladimir Lj , Labopin Myriam , Depei Wu , Yakoub‐Agha Ibrahim , Huynh Anne , Ljungman Per , Schaap Nicolaas , Cornelissen Jan J. , Maillard Natacha , Pioltelli Pietro , Gedde‐Dahl Tobias , Lenhoff Stig , Houhou Mohamed , Esteve Jordi , Mohty Mohamad , Nagler Arnon
Published: October 2017

The aim of the study was to assess the role of allogeneic stem cell transplantation (SCT) in patients diagnosed with BCR‐ABL1‐positive acute myeloid leukemia (AML). Fifty‐seven patients (median age, 48 years, range: 19‐67) with BCR‐ABL1 positive AML undergoing SCT were identified. The majority of the patients (70%) received a TKI before the transplant. At SCT 48 patients were in CR (45 in CR1), while 9 patients were transplanted in a more advanced stage of the disease. MRD was negative (BCR‐ABL1/ABL < 104) at time of SCT in 36.1% (14/40). After SCT, 16 (61.5%) out of 26 patients with MRD positive at transplantation reached MRD negativity. After a median follow‐up of 6.3 years (0.7–14.2), NRM, RI, LFS, OS, and GRFS at 5 years were 18.1%, 37%, 44.2%, 53.8%, and 32.1%, respectively. The cumulative incidence of acute GvHD grade II‐IV was 16.4%, incidence of chronic GvHD 24.9%, and of extensive cGvHD 21.4%, respectively. In patients who received SCT in CR1, 5‐yr NRM, RI, LFS, OS, and GRFS were 15.9%, 36.4%, 46.5%, 59.4%, and 34.9%, respectively. Univariate analysis showed that age (<50 vs. ≥50 years) was associated with RI (5‐yr: 22.7 vs. 50%), LFS (5‐yr: 61.9 vs. 31.8%), and GRFS (5‐yr: 52.4 vs. 18.2%), whereas MRD‐negative status before SCT was associated with an improved GRFS (38.9 vs. 16.7%). We conclude that the outcome of patients <50 years of age with BCR‐ABL1‐positive AML receiving allogeneic SCT in CR is relatively favorable, possibly reflecting the beneficial effect of the use of TKI.
Hereditary stomatocytosis: An underdiagnosed condition
Authors: Andolfo Immacolata , Russo Roberta , Gambale Antonella , Iolascon Achille
Published: October 2017

Hereditary stomatocytoses are a wide class of hemolytic anemias characterized by alterations of ionic flux with increased cation permeability that results in inappropriate shrinkage or swelling of the erythrocytes, and water lost or gained osmotically. The last few years have been crucial for new acquisitions in this field in terms of identifying new causative genes and of studying their pathogenetic mechanisms. This review summarizes the main features of erythrocyte membrane transport diseases, dividing them into forms with either isolated erythroid phenotype (nonsyndromic) or extra‐hematological manifestations (syndromic), and focusing particularly on the most recent advances regarding dehydrated forms of hereditary stomatocytosis and familial pseudohyperkalemia.
A CuII‐based Metal–Organic Framework as an Efficient Photocatalyst for Direct Hydroxylation of Benzene to Phenol in Aqueous Solution
Authors: Zhang Li , Qiu Shuhai , Jiang Guoqing , Jiang Guomin , Tang Ruiren
Published: October 2017

A CuII‐based metal–organic framework (MOF; 1), constructed with imidazole carboxylate ligands (5‐(1 H‐imidazol‐1‐yl)isophthalic acid) and copper(II) ions was prepared and characterized in detail by XRD, Brunauer–Emmett–Teller (BET), thermogravimetric analysis (TGA), and IR methods. Its catalytic performance for the direct hydroxylation of benzene to phenol has been investigated. A benzene conversion of 29 % as well as a high phenol selectivity above 95 % has been obtained at 60 °C in water. The cycling tests showed no significant decrease after five runs, indicating good stability and reuse properties of the CuII‐based MOF (1). The effect of adding the hydroxyl radical scavenger, thiourea, and the ESR spectra of the catalytic system have confirmed the existence of hydroxyl radicals, which indicates the catalytic mechanism follows a Fenton‐type route. This economically and environmentally friendly approach with CuII‐based MOFs is expected to find applications in the hydroxylation of aromatics.
Development of the Japanese version of the Cornell Assessment of Pediatric Delirium
Authors: Hoshino Haruhiko , Matsuishi Yujiro , Shimojo Nobutake , Enomoto Yuki , Kido Takahiro , Inoue Yoshiaki
Published: October 2017

Aim

Delirium is a form of acute cerebral dysfunction and is associated with increased length of hospital stay, mortality, and health‐care costs for adult patients in intensive care. However, in Japan, there are currently no reliable criteria or tools for diagnosing delirium in critically ill pediatric patients. The purpose of this study was to translate the Cornell Assessment of Pediatric Delirium (CAPD)—a screening tool for pediatric delirium—from English to Japanese for use in the diagnosis of delirium for pediatric patients in pediatric intensive care units.

Methods

The back‐translation method was used to ensure equivalence in the Japanese version of the CAPD and its accompanying developmental anchor points. The translation process was repeated by a multidisciplinary committee of medical researchers and clinicians.

Results

The final back‐translated version of the CAPD was submitted to the original author, who gave her approval.

Conclusion

The Japanese CAPD was developed and its effectiveness tested using a standardized procedure. Further study is required to test the validity and reliability of the Japanese version of the CAPD.
Peptide Logic Circuits Based on Chemoenzymatic Ligation for Programmable Cell Apoptosis
Authors: Li Yong , Sun Sujuan , Fan Lin , Hu Shanfang , Huang Yan , Zhang Ke , Nie Zhou , Yao Shouzhou
Published: October 2017

A novel and versatile peptide‐based bio‐logic system capable of regulating cell function is developed using sortase A (SrtA), a peptide ligation enzyme, as a generic processor. By modular peptide design, we demonstrate that mammalian cells apoptosis can be programmed by peptide‐based logic operations, including binary and combination gates (AND, INHIBIT, OR, and AND‐INHIBIT), and a complex sequential logic circuit (multi‐input keypad lock). Moreover, a proof‐of‐concept peptide regulatory circuit was developed to analyze the expression profile of cell‐secreted protein biomarkers and trigger cancer‐cell‐specific apoptosis.
Unlocking the Electrocatalytic Activity of Antimony for CO2 Reduction by Two‐Dimensional Engineering of the Bulk Material
Authors: Li Fengwang , Xue Mianqi , Li Jiezhen , Ma Xinlei , Chen Lu , Zhang Xueji , MacFarlane Douglas R. , Zhang Jie
Published: October 2017

Two‐dimensional (2D) materials are known to be useful in catalysis. Engineering 3D bulk materials into the 2D form can enhance the exposure of the active edge sites, which are believed to be the origin of the high catalytic activity. Reported herein is the production of 2D “few‐layer” antimony (Sb) nanosheets by cathodic exfoliation. Application of this 2D engineering method turns Sb, an inactive material for CO2 reduction in its bulk form, into an active 2D electrocatalyst for reduction of CO2 to formate with high efficiency. The high activity is attributed to the exposure of a large number of catalytically active edge sites. Moreover, this cathodic exfoliation process can be coupled with the anodic exfoliation of graphite in a single‐compartment cell for in situ production of a few‐layer Sb nanosheets and graphene composite. The observed increased activity of this composite is attributed to the strong electronic interaction between graphene and Sb.
Small Molecules Drive Big Improvements in Immuno‐Oncology Therapies
Authors: Huck Bayard R. , Kötzner Lisa , Urbahns Klaus
Published: October 2017

Immuno‐oncology therapies have the potential to revolutionize the armamentarium of available cancer treatments. To further improve clinical response rates, researchers are looking for novel combination regimens, with checkpoint blockade being used as a backbone of the treatment. This Review highlights the significance of small molecules in this approach, which holds promise to provide increased benefit to cancer patients.
Induction of Single‐Handed Helicity of Polyacetylenes Using Mechanically Chiral Rotaxanes as Chiral Sources
Authors: Ishiwari Fumitaka , Nakazono Kazuko , Koyama Yasuhito , Takata Toshikazu
Published: October 2017

Effective induction of preferred‐handed helicity of polyacetylenes by pendant mechanically chiral rotaxanes is discussed. Polyacetylenes possessing optically active mechanically chiral rotaxanes in the side chains were synthesized by the polymerization of the corresponding enantiopure [2]rotaxane‐type ethynyl monomers prepared by the chiral‐phase HPLC separations. The CD Cotton effects revealed that the polyacetylenes took preferred‐handed helical conformations depending on the rotaxane chirality. The preferred‐handed helix was not disturbed by an additional chiral substituent on the rotaxane side chain. These results demonstrate the significance and utility of mechanically chiral rotaxanes for the effective construction of asymmetric fields.
Identifying functional aspects from user reviews for functionality‐based mobile app recommendation
Authors: Xu Xiaoying , Dutta Kaushik , Datta Anindya , Ge Chunmian
Published: October 2017

The explosive growth of mobile apps makes it difficult for users to find their needed apps in a crowded market. An effective mechanism that provides high quality app recommendations becomes necessary. However, existing recommendation techniques tend to recommend similar items but fail to consider users’ functional requirements, making them not effective in the app domain. In this article, we propose a recommendation architecture that can generate app recommendations at the functionality level. We address the redundant recommendation problem in the app domain by highlighting users’ functional requirements, an element that has received scant attention from existing recommendation research. Another main feature of our work is extracting app functionalities from textural user reviews for recommendation. We also propose an effective approach for functionality extraction. Experiments conducted on a real‐world dataset show that our proposed AppRank method outperforms other commonly used recommendation methods. In particular, it doubles the recall value of the second best method under an extremely sparse setting, increases the overall ranking accuracy of the second best method by 14.27%, and retains a high diversity of 0.99.
Hepatocellular uptake of cyclodextrin‐complexed curcumin during liver preservation: A feasibility study
Authors: Saidi Saber Abdelkader , Meurisse Nicolas , Jochmans Ina , Heedfeld Veerle , Wylin Tine , Parkkinen Jaakko , Pirenne Jacques , Monbaliu Diethard , El Feki Abdelfattah , van Pelt Jos
Published: October 2017

The increasing demand for donor organs and the decreasing organ quality is prompting research toward new methods to reduce ischemia reperfusion injury (IRI). Several strategies have been proposed to protect preserved organs from this injury. Before curcumin/dextrin complex (CDC), a potent antioxidant and anti‐inflammatory agent, can be used clinically we need to better understand the intracellular uptake under hypothermic conditions on a rat model of liver donation after circulatory death (DCD) and brain death (DBD). To be able to use the fluorescence of CDC for quantification the stability of CDC in different preservation solutions at 4°C or 37°C was investigated. Livers from Wistar rats were procured after being flushed‐out through the portal vein using CDC‐enriched preservation solutions and stored at 4°C for variable periods. The CDC signal was stable in different preservation solutions over a period of 4 h and allowed the rapid and lasting uptake of curcumin into cells. After 4 h of preservation, CDC was no longer visible microscopically, and HPLC analysis showed very low to non‐detectable tissue levels of CDC, proving metabolization during preservation. However, the distribution of CDC was not affected by warm ischemia damage (p = 0.278) nor by flushing the livers before or after 4 h of cold storage and without a warm preflush. Finally, curcumin reduced oxidative stress, lowered histological injury and did not change gene expression after WI/cold storage. Therefore, the use of CDC flush solution for the initial organ flush can offer a promising approach to the enhancement of liver preservation and the maintenance of its quality.
Genomic Studies Reveal New Aspects of the Biology of DNA Damaging Agents
Authors: Gillingham Dennis , Sauter Basilius
Published: October 2017

A flurry of papers has appeared recently to force a rethinking of our understanding of how chemicals, light, and metal complexes damage our genomes. Conventional wisdom was that damaging agents were indiscriminate and it was statistical bad luck, coupled with evolutionary selection, that drove mutational signatures after exposure of DNA to damaging agents. Recent data, however, suggests that primary DNA damage itself does not drive mutational signatures; instead, it is the selectivity of repair pathways on different regions of the genome that is decisive. In particular, genomic regions shielded by transcription factors or packed densely in nucleosomes are poorly repaired by nucleotide excision repair and are far more susceptible to mutation. There are plenty of approved therapies, the mode‐of‐action of which is to alkylate DNA, and although historically efforts have been focused on understanding how chemicals modify DNA, these new findings suggest that focus should be shifted to understanding genome‐wide repair specificities when different types of alkylation damage occur.
Rational design strategy for optimization of clamping pressure to minimize contact resistance between electrode and current collector while preserving porosity of electrodes in water electrolyzers
Authors: Kishor Koshal , Parashtekar Alhad , Saha Sulay , Sivakumar Sri , Ramkumar Janakaraman , Pala Raj Ganesh S.
Published: October 2017

The compressive clamping pressure at the interface of gas‐diffusion‐layer (GDL) and current collector decreases the contact resistance between them though it reduces the porosity and surface roughness of electrocatalysts, which would in turn decrease the efficiency of an electrolyzer. We explore these issues of trade‐off between porosity versus contact resistance and provide a design heuristic for optimum clamping pressure. The present work provides an estimate of the optimal value of clamping pressure for an alkaline water electrolyzer having membrane electrode assembly (MEA), taking account of the variation in porosity of catalyst layers and contact resistance obtained via half‐cell studies performed at different pressures. Towards this, we define the performance‐index (Φ) which is the ratio of Faradaic current density and resistances resulting from contact‐interfaces in electrolyzers and we suggest that the maxima in Φ corresponds to optimum clamping pressure.
Gold Nanoparticles on Polymer‐Wrapped Carbon Nanotubes: An Efficient and Selective Catalyst for the Electroreduction of CO2
Authors: Jhong Huei‐Ru “Molly” , Tornow Claire E. , Kim Chaerin , Verma Sumit , Oberst Justin L. , Anderson Paul S. , Gewirth Andrew A. , Fujigaya Tsuyohiko , Nakashima Naotoshi , Kenis Paul J. A.
Published: October 2017

Multiple approaches will be needed to reduce the atmospheric CO2 levels, which have been linked to the undesirable effects of global climate change. The electroreduction of CO2 driven by renewable energy is one approach to reduce CO2 emissions while producing chemical building blocks, but current electrocatalysts exhibit low activity and selectivity. Here, we report the structural and electrochemical characterization of a promising catalyst for the electroreduction of CO2 to CO: Au nanoparticles supported on polymer‐wrapped multiwall carbon nanotubes. This catalyst exhibits high selectivity for CO over H2: 80–92 % CO, as well as high activity: partial current density for CO as high as 160 mA cm−2. The observed high activity, originating from a high electrochemically active surface area (23 m2 g−1 Au), in combination with the low loading (0.17 mg cm−2) of the highly dispersed Au nanoparticles underscores the promise of this catalyst for efficient electroreduction of CO2.
Influence of the Anion on the Oxidation of 5‐Hydroxymethylfurfural by Using Ionic‐Polymer‐Supported Platinum Nanoparticle Catalysts
Authors: Siankevich Sviatlana , Mozzettini Simone , Bobbink Felix , Ding Shipeng , Fei Zhaofu , Yan Ning , Dyson Paul J.
Published: October 2017

Platinum nanoparticles stabilized by an imidazolium‐based cross‐linked polymer (with chloride as the counteranion) efficiently catalyzed the oxidation of 5‐hydroxymethylfurfural to form 2,5‐furandicarboxylic acid in water under mild conditions with oxygen as the oxidant. This catalyst system is explored herein by varying the counteranion, that is, replacing chloride by BF4−, PF6−, bis(trifluoromethylsulfonyl)imide, hexanoate, or laurate anions, in the cationic polymer. The counteranion influences the structure of the obtained platinum nanoparticles, the surface electronic properties, and their catalytic activity. The highest reaction rates were obtained with the weakly nucleophilic bis(trifluoromethylsulfonyl)imide anion, which also favored platinum in the zero oxidation state, leading to complete conversion of the substrate and a high yield of 2,5‐furandicarboxylic acid under mild conditions.
Diagnosis Drift and Its Contribution to Polypharmacy
Authors: Reidenberg Marcus M.
Published: October 2017

Diagnoses of drug‐treatable illnesses has drifted to include milder conditions than in the past. Treating them increases the number of drugs given a person, risking polypharmacy, especially in elderly people with multiple conditions. The adverse consequences of polypharmacy are increased costs, confusion when taking drugs, adverse drug events, intermittent adherence with adverse drug discontinuation effects, and unrecognized delayed adverse effects. Deciding what not to treat helps minimize polypharmacy and its consequences.
Designing CdS Mesoporous Networks on Co‐C@Co9S8 Double‐Shelled Nanocages as Redox‐Mediator‐Free Z‐Scheme Photocatalyst
Authors: Reddy D. Amaranatha , Park Hanbit , Gopannagari Madhusudana , Kim Eun Hwa , Lee Seunghee , Kumar D. Praveen , Kim Tae Kyu
Published: October 2017

Designing porous nanostructures with unprecedented functionalities and an effective ability to harvest the maximum energy region of the solar spectrum and suppress the charge‐carrier recombination rate offers promising potential for sustainable energy production. Although several functional porous nanostructures have been developed, high‐efficiency materials are still needed. Herein, we report a new, highly active, noble‐metal‐free, and redox‐mediator‐free Z‐scheme photocatalyst, CdS/Co‐C@Co9S8, for H2 production through water splitting under solar irradiation. The designed photocatalytic system contains open 3 D CdS mesopores as a light absorber for wider solar‐light harvesting. Metal–organicframework‐derived cobalt nanocrystal‐embedded few‐layered carbon@Co9S8 double‐shelled nanocages were used as a co‐semiconductor to hamper the photo charge‐carrier recombination by accelerating the photogenerated electrons and holes from the other semiconductor. The optimized catalyst shows a H2 evolution rate of 26.69 mmol g−1 h−1 under simulated solar irradiation, which is 46 times higher than that of the as‐synthesized CdS mesoporous nanostructures. The apparent quantum yield reached 7.82 % at λ=425 nm in 5 h. The outstanding photocatalytic activity of CdS/Co‐C@Co9S8 reflects the favorable suppression of the charge‐carrier recombination rate, as determined by photoluminescence, photocurrent, and impedance analyses. We believe that the findings reported here may inspire the design of new noble‐metal‐free porous nanohybrids for sustainable H2 production.
Flower‐Like Nickel Phosphide Microballs Assembled by Nanoplates with Exposed High‐Energy (0 0 1) Facets: Efficient Electrocatalyst for the Hydrogen Evolution Reaction
Authors: Wang Honglei , Xie Ying , Cao Hongshuai , Li Yanchao , Li Lin , Xu Zhikun , Wang Xiuwen , Xiong Ni , Pan Kai
Published: October 2017

The fabrication of low‐cost and earth‐abundant electrocatalysts for the hydrogen evolution reaction (HER) over a broad pH range is attractive. In this work, a facile precursor route is developed to synthesize flower‐like nickel phosphide microballs with a diameter of approximately 12 μm. With a controlled phosphorization temperature, flower‐like nickel phosphide microballs with different crystalline structures (Ni5P4 and Ni2P) were obtained easily. Flower‐like Ni5P4 microballs possessed two advantageous features for enhanced HER: fast vectorial electron transfer path along the building block nanoplates and enhanced inherent catalytic activity of each active site for high‐energy (0 0 1) facets. The flower‐like Ni5P4 microballs electrocatalyst thus displayed excellent activity for the HER with a low overpotential (η) of 35.4 mV to reach current densities of 10 mA cm−2 and a small Tafel slope of 48 mV dec−1 in acid solution. In addition, it showed excellent activity in 1 m KOH with η=47 mV at 10 mA cm−2. DFT studies indicated that the free energy of hydrogen adsorbed on the Ni site of Ni5P4 was 0.152 eV, which is smaller than that of the Ni site of Ni2P (0.182 eV). Therefore, flower‐like Ni5P4 microballs exhibited better HER activity than Ni2P, which is consistent with our HER data. This hierarchical structure with exposed high‐energy (0 0 1) facets paves the way to design and synthesize low‐cost, high‐performance catalysts for the HER.
Peripheral Blood Mononuclear Cell Immunophenotyping in Fibrodysplasia Ossificans Progressiva Patients: Evidence for Monocyte DNAM1 Up‐regulation
Authors: Del Zotto Genny , Antonini Francesca , Azzari Irma , Ortolani Claudio , Tripodi Gino , Giacopelli Francesca , Cappato Serena , Moretta Lorenzo , Ravazzolo Roberto , Bocciardi Renata
Published: October 2017

Background

Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disorder caused by sporadic heterozygous mutations inACVR1gene which progressively leads to severe heterotopic ossification. FOP is characterized by episodic flare‐ups triggered by different factors such as viral infections, tissue injuries, vaccinations, or occurring without a recognizable cause. The sporadic course of the disease, the documented presence of an important inflammatory reaction in early lesions and the partial response to corticosteroids support the idea that the immune system, and in particular the innate component, may play a role in FOP pathogenesis. However, an extensive expression profile of the peripheral blood mononuclear cells (PBMC) of FOP patients has never been done.

Methods

In this study, we carried out a wide PBMC immunophenotyping on a cohort of FOP patients and matching controls by multiparametric analysis of the expression of a panel of 37 markers associated with migration, adhesion, inhibition, activation, and cell death of circulating immune cells.

Results

We observed a statistically significant increase of the expression of DNAM1 receptor in patients' monocytes as compared to controls, and little but significant differences in the expression profile of CXCR1 (CD181), CD62L, CXCR4 (CD184), and HLA‐DR molecules.

Conclusions

DNAM1 had been previously shown to play a pivotal role in monocyte migration through the endothelial barrier and the increased expression detected in patients' monocytes might suggest a role of this surface receptor during the early phases of FOP flare‐ups in which the activation of the immune response is believed to represent a crucial event. © 2017 International Clinical Cytometry Society
LEF‐1: Diagnostic utility in distinguishing basaloid neoplasms of the salivary gland
Authors: Schmitt Alessandra C. , Griffith Christopher C. , Cohen Cynthia , Siddiqui Momin T.
Published: October 2017

Background

Lymphoid enhancer binding factor 1 (LEF‐1) has recently been reported as a potential immunohistochemical (IHC) marker for basal cell adenoma (BCA) and other salivary gland tumors, which may contribute to an increased accuracy in differentiating basaloid salivary gland neoplasms. We evaluated the utility of LEF‐1 in fine needle aspiration (FNA) and resection specimens to distinguish pleomorphic adenoma (PA), BCA, basal cell adenocarcinoma (BCAC), and adenoid cystic carcinoma (ACC) as well as in non‐neoplastic salivary gland (NNSG).

Methods

Cases including 66 PA (35 FNA, 31 resections), 12 BCA (5 FNA, 7 resections), 42 ACC (11 FNA, 31 resections), 1 BCAC FNA, and 10 NNSG (5 FNA, 5 resections) were obtained and stained for LEF‐1.

Results

On cell block (CB), 51% of PA and 60% of BCA were LEF‐1 positive while 91% of ACC were LEF‐1 negative. Among resections, there was a higher percentage of LEF‐1 positive PA (84%) and BCA (86%), and a higher percentage of LEF‐1 negative ACC (97%). LEF‐1 staining had a low to moderate sensitivity for detecting benign basaloid neoplasms on FNA CB and resection specimens (52.5% and 84%, respectively), but a higher specificity (92% and 97% respectively), and positive predictive value (95% and 97% respectively).

Conclusion

When comparing benign (PA and BCA) and the most common malignant basaloid salivary gland tumor (ACC), positive LEF‐1 favors a benign neoplasm. Additional studies with LEF‐1, specifically including other rare basaloid salivary gland neoplasms are needed to further clarify the role of LEF‐1 in diagnosing these lesions on FNA.
Environmental proteomics reveals taxonomic and functional changes in an enriched aquatic ecosystem
Authors: Northrop Amanda C. , Brooks Rachel K. , Ellison Aaron M. , Gotelli Nicholas J. , Ballif Bryan A.
Published: October 2017

Aquatic ecosystem enrichment can lead to distinct and irreversible changes to undesirable states. Understanding changes in active microbial community function and composition following organic matter loading in enriched ecosystems can help identify biomarkers of such state changes. In a field experiment, we enriched replicate aquatic ecosystems in the pitchers of the northern pitcher plant, Sarracenia purpurea. Shotgun metaproteomics using a custom metagenomic database identified proteins, molecular pathways, and contributing microbial taxa that differentiated control ecosystems from those that were enriched. The number of microbial taxa contributing to protein expression was comparable between treatments; however, taxonomic evenness was higher in controls. Functionally active bacterial composition differed significantly among treatments and was more divergent in control pitchers than in enriched pitchers. Aerobic and facultative anaerobic bacteria contributed most to identified proteins in control and enriched ecosystems, respectively. The molecular pathways and contributing taxa in enriched pitcher ecosystems were similar to those found in larger enriched aquatic ecosystems and are consistent with microbial processes occurring at the base of detrital food webs. Detectable differences between protein profiles of enriched and control ecosystems suggest that a time series of environmental proteomics data may identify protein biomarkers of impending state changes to enriched states.
Characterization of a novel capsaicin/heat ongoing pain model
Authors: Price R.C. , Gandhi W. , Nadeau C. , Tarnavskiy R. , Qu A. , Fahey E. , Stone L. , Schweinhardt P.
Published: October 2017

Background

Human experimental pain models provide an important translational link between pre‐clinical models and clinical pain. Using topical capsaicin and continuous heat application, the novel capsaicin/heat ongoing pain (CHOP) model induces long‐lasting experimental pain of which the perceived intensity can be individually adjusted.

Methods

In the CHOP model, capsaicin or control cream is applied to a 10 × 10 cm skin area and a heating pad is applied over the area after cream removal. Two experiments in healthy participants were performed for model characterization. In Experiment 1, a constant temperature was applied for 60 min; in Experiment 2, temperature was adjusted to maintain a constant perceived intensity for 60 min.

Results

Experiment 1: across participants, constant temperature induced initial habituation followed by an increase in sensation back to baseline. Cluster analysis revealed that half the participants sensitized to the constant temperature, while the other half did not. The degree of sensitization was related to the baseline pain unpleasantness, relative to pain intensity. Experiment 2: constant perceived intensity was achieved in the painful and a non‐painful control condition. The two conditions did not differ regarding possibly confounding variables, including blood pressure, heart rate, inflammation or physiological stress as measured by surrogate markers. Secondary allodynia and hyperalgesia were reported more following painful compared to control stimulation. Sensitizers as determined in Experiment 1 were also more pain sensitive in Experiment 2.

Conclusion

The CHOP model reproduces some aspects of clinical pain, such as longer duration, sensitization, secondary allodynia and hyperalgesia.

Significance

Here we demonstrate a novel pain model that can be applied for up to an hour without tissue damage. The CHOP model allows for investigation of primary and secondary hyperalgesia as well as top‐down influences on sensitization, thereby providing an experimental model that can be used to assess clinically‐oriented questions.
Copper‐based Metal‐organic Framework Applied in the Development of an Electrochemical Biomimetic Sensor for Catechol Determination
Authors: Brondani Daniela , Zapp Eduardo , da Silva Heying Renata , de Souza Bernardo , Cruz Vieira Iolanda
Published: October 2017

In this study, the synthesis and characterization of a Cu‐based metal‐organic framework (MOF) [Cu3(BTC)2(H2O)3]n (where BTC=benzene‐1,3,5‐tricarboxylate), known as HKUST‐1, were performed. The Cu‐MOF was applied in the modification of a carbon paste to obtain a biomimetic sensor for the electrochemical determination of catechol. Kinetic assays confirmed that the Cu‐MOF acts as a catalyst for the oxidation of catechol and it can be considered as a catechol oxidase mimetic. Under optimized conditions, the calibration curve for catechol presented a linear range of 8.0×10−7 to 3.2×10−5 mol L−1, with detection limit of=1.0×10−7 mol L−1. The sensor demonstrated good intra‐day repeatability and inter‐electrode reproducibility (relative standard deviations of 3.8 % (n=10) and 4.3 % (n=6), respectively). In the selectivity study, an adequate peak‐to‐peak separation was observed for hydroquinone and uric acid in relation to catechol, demonstrating that this sensor has the potential for use in the simultaneous determination of these compounds. This sensor was successfully applied in the determination of catechol in water samples.