bluuebunny/crossref_metadata_2025 huggingface dataset:
Carbonylmetallates—A Special Family of Nucleophiles in Aromatic and Vinylic Substitution Reactions
Authors: Sazonov Petr K. , Beletskaya Irina P.
Published: January 2016

Carbonylmetallates, [M(CO)nL]−, anionic transition‐metal carbonyl complexes, represent a large family of metal‐centered nucleophiles, and studying carbonylmetallates allows us to understand the differences in the behavior of the metal‐centered complexes versus heteroatom‐based nucleophiles. The mechanisms of carbonylmetallate reactions with aryl‐ and alkenyl halides have been examined by employing radical and, especially, carbanion trapping techniques. Carbonylmetallates show a marked preference for halogenophilic attack, and nucleophilic substitution with carbonylmetallates is often not a direct process, but proceeds through the initial attack at halogen with subsequent coupling of carbanion and HalM(CO)nL intermediates. Factors governing the competition between the halogenophilic and more common “carbophilic” reaction pathways, as well as the means of predicting the actual course of reaction are discussed. The review also considers other aspects of carbonylmetallate reactivity, including ion‐pairing effects, radical‐mediated nucleophilic substitution pathways, and the carbonylmetallate nucleophilicity scale in the reactions with π‐electrophiles.
Selective localization of myosin‐I proteins in macropinosomes and actin waves
Authors: Brzeska Hanna , Koech Hilary , Pridham Kevin J. , Korn Edward D. , Titus Margaret A.
Published: January 2016

Class I myosins are widely expressed with roles in endocytosis and cell migration in a variety of cell types. Dictyostelium express multiple myosin Is, including three short‐tailed (Myo1A, Myo1E, Myo1F) and three long‐tailed (Myo1B, Myo1C, Myo1D). Here we report the molecular basis of the specific localizations of short‐tailed Myo1A, Myo1E, and Myo1F compared to our previously determined localization of long‐tailed Myo1B. Myo1A and Myo1B have common and unique localizations consistent with the various features of their tail region; specifically the BH sites in their tails are required for their association with the plasma membrane and heads are sufficient for relocalization to the front of polarized cells. Myo1A does not localize to actin waves and macropinocytic protrusions, in agreement with the absence of a tail region which is required for these localizations of Myo1B. However, in spite of the overall similarity of their domain structures, the cellular distributions of Myo1E and Myo1F are quite different from Myo1A. Myo1E and Myo1F, but not Myo1A, are associated with macropinocytic cups and actin waves. The localizations of Myo1E and Myo1F in macropinocytic structures and actin waves differ from the localization of Myo1B. Myo1B colocalizes with F‐actin in the actin waves and at the tips of mature macropinocytic cups whereas Myo1E and Myo1F are in the interior of actin waves and along the entire surface of macropinocytic cups. Our results point to different mechanisms of targeting of short‐ and long‐tailed myosin Is, and are consistent with these myosins having both shared and divergent cellular functions. © 2016 Wiley Periodicals, Inc.
Screening, Synthesis, and In Vitro Evaluation of Vinyl Sulfones as Inhibitors of Complement‐Dependent Cytotoxicity in Neuromyelitis Optica
Authors: Ju Eun Ji , Yeon Seul Ki , Park Jong‐Hyun , Cheon So Young , Choi Ji Won , Ha Taehwan , Jang Bo Ko , Kim Siwon , Kang Yong Gu , Hwang Hayoung , Cho Sung Jin , Cheong Eunji , Bahn Yong Sun , Pae Ae Nim , Kim Sung Min , Park Ki Duk
Published: January 2016

Neuromyelitis optica (NMO) is a demyelinating autoimmune disease of the optic nerve and spinal cord triggered by binding of NMO‐specific immunoglobulin G (NMO‐IgG) auto‐antibodies to the water channel aquaporin‐4 (AQP4) in astrocytes. To find potential NMO therapeutics, a screening system was established and used to identify inhibitors of NMO‐IgG‐mediated complement‐dependent cytotoxicity (CDC). The screening of approximately 400 compounds yielded potent hit compounds with inhibitory effects against CDC in U87‐MG cells expressing human AQP4. Derivatives of the hit compounds were synthesized and evaluated for their inhibition of CDC. Of the small molecules synthesized, (E)‐1‐(2‐((4‐methoxyphenyl)sulfonyl)vinyl)‐[4‐[(3‐trifluoromethyl)phenyl] methoxy]benzene (5 c) showed the most potent activity in both stably transfected U87‐MG cells and mice‐derived astrocytes. The results of this study suggest that 5 c, which targets NMO‐IgG‐specific CDC, may be useful as a research tool and a potential candidate for therapeutic development for the treatment of NMO.
Nonplasmonic Hot‐Electron Photocurrents from Mn‐Doped Quantum Dots in Photoelectrochemical Cells
Authors: Dong Yitong , Rossi Daniel , Parobek David , Son Dong Hee
Published: January 2016

We report the measurement of the hot‐electron current in a photoelectrochemical cell constructed from a glass/ITO/Al2O3 (ITO=indium tin oxide) electrode coated with Mn‐doped quantum dots, where hot electrons with a large excess kinetic energy were produced through upconversion of the excitons into hot electron hole pairs under photoexcitation at 3 eV. In our recent study (J. Am. Chem. Soc. 2015, 137, 5549), we demonstrated the generation of hot electrons in Mn‐doped II–VI semiconductor quantum dots and their usefulness in photocatalytic H2 production reaction, taking advantage of the more efficient charge transfer of hot electrons compared with band‐edge electrons. Here, we show that hot electrons produced in Mn‐doped CdS/ZnS quantum dots possess sufficient kinetic energy to overcome the energy barrier from a 5.4–7.5 nm thick Al2O3 layer producing a hot‐electron current in photoelectrochemical cell. This work demonstrates the possibility of harvesting hot electrons not only at the interface of the doped quantum dot surface, but also far away from it, thus taking advantage of the capability of hot electrons for long‐range electron transfer across a thick energy barrier.
A modified poisson distribution for smartphone background traffic in cellular networks
Authors: Zhang Sa , Zhao Zhuyan , Guan Hao , Yang Hongwen
Published: January 2016

For the emerging applications such as Google Talk, Facebook, Skype and QQ, to mention a few, which run on smartphones, background traffic has become one of the significant issues in system design and optimization. Because of the complicated user behavior and interaction, the assumptions underlying the Poisson process model cannot be met; the Poisson distribution cannot approximate the distribution of background traffic arrivals accurately. In this paper, we propose a model, which can better fit the background traffic arrivals of smartphones than the Poisson distribution. The proposed model is a linear transformation of the Poisson distribution and is specified by three parameters, (a,b,λ), which can be estimated from the measured sample's mean, variance, and third central moment. Simulation results have corroborated the fitness of the proposed model in both single and mixed applications scenarios. In addition, we have also observed that the normalized parameters, (a,b0,λ0), of each application is independent of the user number and completely characterized by the type of application. Hence, with the given trace cumulative distribution functions of all applications, the proposed modified Poisson distribution can be used as a tool for modeling and analyzing background traffic arrivals with arbitrary user numbers and mixed applications. Copyright © 2016 John Wiley & Sons, Ltd.
DNA degradation in liquid‐based cytology and its comparison with conventional smear
Authors: Kim Wook Youn , Oh Seo Young , Kim Hyunkyung , Hwang Tae Sook
Published: January 2016

Background

In fine needle aspiration biopsy (FNAB) of thyroid nodules, LBC is adopted in most of the hospitals and clinics in Korea for its convenience. BRAF mutation test has been introduced as an important ancillary test, but its applicability has not been completely proven with LBC samples.

Methods

Five aspirates from thyroidectomy specimens were simultaneously processed into LBC and CS slides, in which BRAF mutation tests were performed using three primer sets with PCR products of 72, 164, and 226 base pairs (bp) at 6, 9, and 12 months after processing. In addition, BRAF mutation tests were performed in nine clinical samples that had been prepared by LBC or CS and stored for 3–5 years after processing.

Results

At 9 months after processing, LBC failed to provide DNA of sufficient quality for PCR, whereas CS succeeded with primers for amplifying a 226 bp fragment. Furthermore, CS had successful amplification of DNA despite a delay of more than 1 year. The failure of DNA amplification in LBC was overcome by using primers to amplify shorter PCR products, suggesting that DNA degradation occurred in LBC. However, false positive or negative results were observed in primers for amplifying shorter size. The kind of preservative solutions used in LBC did not affect test results.

Conclusion

LBC may have disadvantages in long‐term DNA preservation because of its accelerated DNA degradation compared with alcohol‐fixed CS. Using primers to amplify shorter size fragments might be helpful in mitigating loss of signal due to DNA degradation in LBC. Diagn. Cytopathol. 2016;44:450–458. © 2016 Wiley Periodicals, Inc.
Lanthanide Complexation of 2,6‐Bis(5,6‐dipyridyl‐1,2,4‐triazinyl)pyr­idine – Solvent‐ and Lanthanide‐Ion‐Controlled Ligand Coordination Mode and Denticity
Authors: Bhattacharyya Arunasis , Forster Paul M. , Rego Daniel B. , Czerwinski Kenneth R.
Published: January 2016

2,6‐Bis(5,6‐dipyridyl‐1,2,4‐triazinyl)pyridine (PyBTP) is an interesting ligand owing to the possible variation of its coordination sites and denticity in complexation. Therefore, solution and solid‐phase lanthanide complexations were studied with PyBTP in two solvents, viz., acetonitrile and methanol, through various spectroscopic and single‐crystal X‐ray diffraction techniques. The results from all of these studies consistently showed the interesting observation of solvent‐dependent changes to the ligand coordination mode and denticity, which are reported for the first time for trivalent lanthanide (Ln3+) complexes. The ligand coordination is affected by the size of the lanthanide ion. This observation can provide clues for the development of intra‐lanthanide and lanthanide–actinide separation methods through the exploitation of the variable complexing behaviour of a particular ligand.
Absolute moral standards and global identity as independent predictors of collective action against global injustice
Authors: Barth Markus , Jugert Philipp , Wutzler Markus , Fritsche Immo
Published: January 2016

Today's global challenges necessitate the cooperation of the international community. In two studies, this paper investigates global identity and absolute moral standards as two important predictors of solidarity and collective action intentions. In Study 1 (N = 450), we found evidence for parallel direct effects of global identity and absolute standards on intergroup solidarity and indirectly on collective action intentions. Similar, albeit weaker, effects were found for real behavior (a donation). Study 2 (N = 124) experimentally manipulated participants' moral standard. Participants in the absolute standard condition were more willing to participate in collective action than participants who were experimentally focused on a gradual standard. Additionally, Study 2 replicated the indirect effects of global identity and absolute moral standards that we found in Study 1. The results show the important role of global identity and absolute moral standards as independent motivators of collective action.
CE‐UV for the characterization of passion fruit juices provenance by amino acids profile with the aid of chemometric tools
Authors: Passos Heloisa Moretti , Cieslarova Zuzana , Simionato Ana Valéria Colnaghi
Published: January 2016

A separation method was developed in order to quantify free amino acids in passion fruit juices using CE‐UV. A selective derivatization reaction with FMOC followed by MEKC analysis was chosen due to the highly interconnected mobilities of the analytes, enabling the separation of 22 amino acids by lipophilicity differences, as will be further discussed. To achieve such results, the method was optimized concerning BGE composition (concentrations, pH, and addition of organic modifier) and running conditions (temperature and applied voltage). The optimized running conditions were: a BGE composed by 60 mmol/L borate buffer at pH 10.1, 30 mmol/L SDS and 5 % methanol; running for 40 min at 23°C and 25 kV. The method was validated and applied on eight brands plus one fresh natural juice, detecting 12 amino acids. Quantification of six analytes combined with principal component analysis was capable to characterize different types of juices and showed potential to detect adulteration on industrial juices. Glutamic acid was found to be the most concentrated amino acid in all juices, exceeding 1 g/L in all samples and was also crucial for the correct classification of a natural juice, which presented a concentration of 22 g/L.
Improved ε‐poly‐l‐lysine productivity partly resulting from rapid cell growth in cultures using a glucose–glycerol mixed carbon source
Authors: Zeng Xin , Chen Xu‐Sheng , Ren Xi‐Dong , Wang Liang , Gao Yang , Mao Zhong‐Gui
Published: January 2016

Productivity enhancements with mixed carbon sources are usually accompanied by simultaneous improvement of cell growth. However, whether the enhanced cell growth in mixed carbon sources influences the biochemical productivity of ε‐poly‐l‐lysine (ε‐PL) still remains unclear. In this study, we investigated the effect of growth rate on the ε‐PL productivity in a glucose–glycerol mixed carbon source. Based on the typical ε‐PL fed batch fermentation, chemostat culture and relevant physiological analyses were carried out. The ε‐PL productivity was positively correlated to the growth rate ranging from 0.02 to 0.06 h−1. The primary metabolism activity was enhanced at higher growth rate, providing sufficient precursor l‐lysine and energy for ε‐PL production. Meanwhile, these two key elements were equally important for biomass production, which could be quickly produced when the cells were fast growing. In addition, rapid growth also strengthened the antioxidant capacity of cells to defend potential oxidative stress. The positive correlation between the growth rate and ε‐PL productivity indicated that the improvement of ε‐PL productivity in the mixed carbon source was partly attributed to the simultaneously enhanced cell growth. Information obtained may provide references for further studies on other secondary biochemicals’ production using mixed carbon sources.
Exposure to persistent organic pollutants and sperm DNA methylation changes in Arctic and European populations
Authors: Consales Claudia , Toft Gunnar , Leter Giorgio , Bonde Jens Peter E. , Uccelli Raffaella , Pacchierotti Francesca , Eleuteri Patrizia , Jönsson Bo A.G. , Giwercman Aleksander , Pedersen Henning S. , Struciński Paweł , Góralczyk Katarzyna , Zviezdai Valentyna , Spanò Marcello
Published: January 2016

Persistent organic pollutants (POPs), such as PCBs (polychlorinated biphenyls) and DDT [1,1,1‐trichloro‐2,2‐bis(4‐chlorophenyl)ethane], are environmental contaminants with potential endocrine disrupting activity. DNA methylation levels in peripheral blood lymphocytes have been associated with serum concentrations of POPs in Greenland Inuit and Korean populations. Greenland Inuits are characterized by the highest worldwide POP levels. In this cross‐sectional study we evaluated the relationship between serum POP concentrations and DNA methylation levels in sperm of non‐occupationally exposed fertile men from Greenland, Warsaw (Poland), and Kharkiv (Ukraine). Serum levels of PCB‐153 [1,2,4‐trichloro‐5‐(2,4,5‐trichlorophenyl)benzene], as a proxy of the total PCBs body burden, and of p,p'‐DDE [1,1‐dichloro‐2,2‐bis(4‐chlorophenyl)ethylene], the main metabolite of DDT were measured. Sperm DNA methylation level was assessed globally by flow cytometric (FCM) immunodetection of 5‐methyl‐cytosines and at specific repetitive DNA sequences (Alu, LINE‐1, Satα) by PCR‐pyrosequencing after bisulfite conversion. Multivariate linear regression analysis was applied to investigate correlations between serum POP concentrations and DNA methylation. No consistent associations between exposure to POPs and sperm DNA methylation at repetitive DNA sequences were detected. A statistically significant global decrease in methylation was associated with exposure to either POP by FCM analysis. This is the first study to investigate environmental exposure to POPs and DNA methylation levels considering sperm as the target cells. Although POP exposure appears to have a limited negative impact on sperm DNA methylation levels in adult males, the global hypomethylation detected by one of the methods applied suggests that further investigation is warranted. Environ. Mol. Mutagen. 57:200–209, 2016. © 2016 Wiley Periodicals, Inc.
Super‐hydrophilic porous TiO2‐ZnO composite thin films without light irradiation
Authors: Li Zhenzi , Hou Yan , Ma Baohua , Wu Xiaoyan , Xing Zipeng , Li Kang
Published: January 2016

A serial of porous TiO2‐ZnO composite thin films have been successfully synthesized by a facile one‐pot dip‐coating method, utilizing the amphiphilic triblock copolymer Pluronic P123 as the surfactant, and the Ti(OnBu)4 and ZnCl2 as the inorganic sources. The resultant materials are characterized in detail by X‐ray diffraction, atomic force microscopy, scanning electron microscopy and water contact angle measurements. The results indicate that the porous TiO2‐ZnO thin film after being calcined at 550°C possesses superhydrophilicity without light irradiation, which could be attributed to the high surface roughness and porous structure. What's more, it exhibits the long‐term superhydrophilic stability, which would have potential applications in fields of environment. © 2016 American Institute of Chemical Engineers Environ Prog, 35: 1121–1124, 2016
Detailed chemical kinetics for thermal decomposition of low molecular weight‐methyl esters generated by using biodiesel fuel
Authors: Thang Phan Quang , Maeda Yasuaki , Trung Nguyen Quang , Takenaka Norimichi
Published: January 2016

Low molecular weight‐methyl ester (LMW‐ME), which was reported in our previous study [1], was generated by the use of biodiesel fuel (BDF) with a diesel power generator. In this article, the detailed chemical kinetics for the thermal decomposition of LMW‐MEs was investigated at atmospheric pressure and a temperature range of 773 to 973 K. Six standards of LMW‐MEs were used for thermal decomposition in a continuous flow reactor. The kinetic data, such as reaction orders, activation energies, and rate constants, were then calculated. The reaction orders and activation energies of the thermal decomposition reactions of C4, C5, C6, C7, C8, and C9 were 1.13, 0.96, 1.17, 0.80, 0.99, 0.84, and 312.04, 117.37, 87.29, 62.94, 74.80, 75.79 kJ mol−1, respectively. The decomposition of LMW‐MEs with higher carbon numbers was faster than those with smaller carbon numbers, except for C8. The C4 methyl ester was stable and abundant in the product of the decomposition as well as in the exhausted gas from the engine combustion using BDF. This kinetic data will be applied to modeling study on BDF decomposition and engine technologies to mitigate toxic emissions from BDF combustion. © 2016 American Institute of Chemical Engineers Environ Prog, 35: 1190–1197, 2016
Wood and sediment storage and dynamics in river corridors
Authors: Wohl Ellen , Scott Daniel N.
Published: January 2016

Large wood along rivers influences entrainment, transport, and storage of mineral sediment and particulate organic matter. We review how wood alters sediment dynamics and explore patterns among volumes of in‐stream wood, sediment storage, and residual pools for dispersed pieces of wood, logjams, and beaver dams. We hypothesized that: volume of sediment per unit area of channel stored in association with wood is inversely proportional to drainage area; the form of sediment storage changes downstream; sediment storage correlates with wood load; the residual volume of pools created in association with wood correlates inversely with drainage area; and volume of sediment stored behind beaver dams correlates with pond area. Lack of data from larger drainage areas limits tests of these hypotheses, but the analyses suggest that sediment volume correlates positively with drainage area and wood volume. The form of sediment storage in relation to wood appears to change downstream, with wedges of sediment upstream from jammed steps most prevalent in small, steep channels and more dispersed sediment storage in lower gradient channels. Pool volume correlates positively with wood volume and negatively with channel gradient. Sediment volume correlates well with beaver pond area.

More abundant in‐stream wood and beaver populations present historically equated to greater sediment storage within river corridors and greater residual pool volume. One implication of these changes is that protecting and re‐introducing wood and beavers can be used to restore rivers. This review of the existing literature on wood and sediment dynamics highlights the lack of studies on larger rivers. Copyright © 2016 John Wiley & Sons, Ltd.
Degradation and transformation of 17α-estradiol in water–sediment systems under controlled aerobic and anaerobic conditions
Authors: Robinson Joseph A. , Ma Qingli , Staveley Jane P. , Smolenski Walter J. , Ericson Jon
Published: January 2016

One of the principal metabolites in cattle excreta following the administration of Synovex® ONE, which contains estradiol benzoate and trenbolone acetate, is 17α-estradiol. As part of the environmental assessment of the use of Synovex ONE, data were generated to characterize the fate of 17α-estradiol in the environment. Studies were conducted to determine the degradation and transformation of 17α-[14C]-estradiol in 2 representative water–sediment systems each under aerobic and anaerobic conditions. The same transformation products—estriol, 17β-estradiol, and estrone—were formed, principally in the sediment phase, under both conditions in both systems. From the production of these transformation products, the 50% disappearance time (DT50) values of estrone and 17β-estradiol were determined, along with the DT50 values of 17α-estradiol and the total drug (17α-estradiol + 17β-estradiol + estrone). The results indicate that 17 α-[14C]-estradiol was more persistent under anaerobic conditions than under aerobic conditions and that 17 α-[14C]-estradiol was less persistent than its transformation products. The DT50 values for the total system (aqueous and sediment phases) and for the total residues (17α-estradiol, 17β-estradiol, and estrone) were selected for use in modeling the environmental fate of estradiol benzoate. For aerobic degradation in the water–sediment system, the DT50 was 31.1 d, and it was 107.8 d for the anaerobic system. Environ Toxicol Chem 2017;36:621–629. © 2016 SETAC
The superficial white matter in Alzheimer's disease
Authors: Phillips Owen R , Joshi Shantanu H. , Piras Fabrizio , Orfei Maria Donata , Iorio Mariangela , Narr Katherine L. , Shattuck David W. , Caltagirone Carlo , Spalletta Gianfranco , Di Paola Margherita
Published: January 2016

White matter abnormalities have been shown in the large deep fibers of Alzheimer's disease patients. However, the late myelinating superficial white matter comprised of intracortical myelin and short‐range association fibers has not received much attention. To investigate this area, we extracted a surface corresponding to the superficial white matter beneath the cortex and then applied a cortical pattern‐matching approach which allowed us to register and subsequently sample diffusivity along thousands of points at the interface between the gray matter and white matter in 44 patients with Alzheimer's disease (Age: 71.02 ± 5.84, 16M/28F) and 47 healthy controls (Age 69.23 ± 4.45, 19M/28F). In patients we found an overall increase in the axial and radial diffusivity across most of the superficial white matter (P < 0.001) with increases in diffusivity of more than 20% in the bilateral parahippocampal regions and the temporal and frontal lobes. Furthermore, diffusivity correlated with the cognitive deficits measured by the Mini‐Mental State Examination scores (P < 0.001). The superficial white matter has a unique microstructure and is critical for the integration of multimodal information during brain maturation and aging. Here we show that there are major abnormalities in patients and the deterioration of these fibers relates to clinical symptoms in Alzheimer's disease. Hum Brain Mapp 37:1321‐1334, 2016. © 2016 Wiley Periodicals, Inc.
Hemangiopericytoma arising from the cartilage of the external auditory canal
Authors: Castiglione Melina , Nardo Luciano , Ottaviani Francesco
Published: January 2016

Background

Hemangiopericytomas (HPCs) are soft tissue tumors with histological variability and unpredictable clinical and biological behavior. HPCs in the head and neck are uncommon, the growth pattern is nonspecific; thus, diagnosis is often made by exclusion.

Methods

A 43‐year‐old man complained of a short history of right ear pain associated with a growing mass in the right external auditory canal. Subsequent hearing loss in the right ear brought the patient to undergo a CT scan and an MRI. The relevant literature was also reviewed.

Results

The imaging revealed a neoplasm arising from the floor of the right external auditory canal. The neoplasm was removed with the diagnosis of HPC.

Conclusion

The literature reports few cases of HPC of the external auditory canal. Their rarity in this area leads to difficulties in diagnosis. Morphology is not predictive of their behavior, so close follow‐up is mandatory for their correct management. © 2015 Wiley Periodicals, Inc. Head Neck 38: E108–E110, 2016
A new HIF‐1α/RANTES‐driven pathway to hepatocellular carcinoma mediated by germline haploinsufficiency of SART1/HAF in mice
Authors: Koh Mei Yee , Gagea Mihai , Sargis Timothy , Lemos Robert , Grandjean Geoffrey , Charbono Adriana , Bekiaris Vasileos , Sedy John , Kiriakova Galina , Liu Xiuping , Roberts Lewis R. , Ware Carl , Powis Garth
Published: January 2016

The hypoxia‐inducible factor (HIF), HIF‐1, is a central regulator of the response to low oxygen or inflammatory stress and plays an essential role in survival and function of immune cells. However, the mechanisms regulating nonhypoxic induction of HIF‐1 remain unclear. Here, we assess the impact of germline heterozygosity of a novel, oxygen‐independent ubiquitin ligase for HIF‐1α: hypoxia‐associated factor (HAF; encoded by SART1). SART1−/−
mice were embryonic lethal, whereas male SART1+/−
mice spontaneously recapitulated key features of nonalcoholic steatohepatitis (NASH)‐driven hepatocellular carcinoma (HCC), including steatosis, fibrosis, and inflammatory cytokine production. Male, but not female, SART1+/−
mice showed significant up‐regulation of HIF‐1α in circulating and liver‐infiltrating immune cells, but not in hepatocytes, before development of malignancy. Additionally, Kupffer cells derived from male, but not female, SART1+/−
mice produced increased levels of the HIF‐1‐dependent chemokine, regulated on activation, normal T‐cell expressed and secreted (RANTES), compared to wild type. This was associated with increased liver‐neutrophilic infiltration, whereas infiltration of lymphocytes and macrophages were not significantly different. Neutralization of circulating RANTES decreased liver neutrophilic infiltration and attenuated HCC tumor initiation/growth in SART1+/−
mice. Conclusion: This work establishes a new tumor‐suppressor role for HAF in immune cell function by preventing inappropriate HIF‐1 activation in male mice and identifies RANTES as a novel therapeutic target for NASH and NASH‐driven HCC. (Hepatology 2016;63:1576‐1591)
5‐Alpha reductase inhibitor use and prostate cancer survival in the Finnish Prostate Cancer Screening Trial
Authors: Murtola Teemu J. , Karppa Elina K. , Taari Kimmo , Talala Kirsi , Tammela Teuvo LJ , Auvinen Anssi
Published: January 2016

Randomized clinical trials have shown that use of 5α‐reductase inhibitors (5‐ARIs) lowers overall prostate cancer (PCa) risk compared to placebo, while the proportion of Gleason 8–10 tumors is elevated. It is unknown whether this affects PCa‐specific survival. We studied disease‐specific survival by 5‐ARI usage in a cohort of 6,537 prostate cancer cases diagnosed in the Finnish Prostate Cancer Screening Trial and linked to the national prescription database for information on medication use. Cox proportional hazards regression was used to estimate hazard ratios and 95% confidence intervals for prostate cancer‐specific deaths. For comparison, survival among alpha‐blocker users was also evaluated. During the median follow‐up of 7.5 years after diagnosis a total of 2,478 men died; 617 due to prostate cancer and 1,861 due to other causes. The risk of prostate cancer death did not differ between 5‐ARI users and nonusers (multivariable adjusted HR 0.94, 95% CI 0.72–1.24 and HR 0.98, 95% CI 0.69–1.41 for usage before and after the diagnosis, respectively). Alpha‐blocker usage both before and after diagnosis was associated with increased risk of prostate cancer death (HR 1.29, 95% CI 1.08–1.54 and HR 1.56, 95% CI 1.30–1.86, respectively). The risk increase vanished in long‐term alpha‐blocker usage. Use of 5‐ARIs does not appear to affect prostate cancer mortality when used in management of benign prostatic hyperplasia. Increased risk associated with alpha‐blocker usage should prompt further exploration on the prognostic role of lower urinary tract symptoms.
Cell shape and the presentation of adhesion ligands guide smooth muscle myogenesis
Authors: Zhang Douglas , Sun Michael B. , Lee Junmin , Abdeen Amr A. , Kilian Kristopher A.
Published: January 2016

The reliable generation of smooth muscle cells is important for a number of tissue engineering applications. Human mesenchymal stem cells (MSCs) are a promising progenitor of smooth muscle, with high expression of smooth muscle markers observed in a fraction of isolated cells, which can be increased by introduction of soluble supplements that direct differentiation. Here we demonstrate a new micropatterning technique, where peptides of different ligand affinity can be microcontact printed onto an inert background, to explore MSC differentiation to smooth muscle through controlled biochemical and biophysical cues alone. Using copper‐catalyzed alkyne‐azide cycloaddition (CuAAC), we patterned our surfaces with RGD peptide ligands—both a linear peptide with low integrin affinity and a cyclic version with high integrin affinity—for the culture of MSCs in shapes with various aspect ratios. At low aspect ratio, ligand affinity is a prime determinant for smooth muscle differentiation, while at high aspect ratio, ligand affinity has less of an effect. Pathway analysis reveals a role for focal adhesion turnover, Rac1, RhoA/ROCK, and calpain during smooth muscle differentiation of MSCs in response to cell shape and the affinity of the cell adhesion interface. Controlling integrin‐ligand affinity at the biomaterials interface is important for mediating adhesion but may also prove useful for directing smooth muscle myogenesis. Peptide patterning enables the systematic investigation of single to multiple peptides derived from any protein, at different densities across a biomaterials surface, which has the potential to direct multiple MSC differentiation outcomes without the need for soluble supplements. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1212–1220, 2016.
Establishing an institutional therapeutic apheresis registry
Authors: Mann Steven A. , McCleskey Brandi , Marques Marisa B. , Adamski Jill
Published: January 2016

Apheresis was first performed as a therapeutic procedure in the 1950s. The first national therapeutic apheresis (TA) registry was established in Canada in 1981 and other national registries followed, including two attempts at establishing an international TA registry. There is no national registry in the United States. Our large, academic, tertiary hospital has a very active TA service. We created a TA database to track all procedures performed by the apheresis service by transferring data from paper appointment logs and the electronic medical records into a Microsoft Access database. Retrospective data from each TA procedure performed at UAB from January 1, 2003 through December 31, 2012 were entered, including the type of procedure, indication, date, and patient demographics. Microsoft Excel was used for data analysis. During the 10‐year period, our TA service treated 1,060 patients and performed 11,718 procedures. Of these patients, 70% received therapeutic plasma exchange (TPE), 21% received extracorporeal photopheresis (ECP), 4.5% received red cell exchange (RCE), 4.2% received leukocytapheresis, and 0.6% underwent platelet depletion. Among the procedures, 54% were TPEs, 44% were ECPs, 1.3% were RCEs, 0.5% were leukocytaphereses, and 0.1% were platelet depletions. According to the current literature, national and international TA use is underreported. We believe that the UAB TA registry provides useful information about TA practices in our region and can serve as a model for other institutions. Furthermore, data from multiple institutional registries can be used for clinical research to increase the available evidence for the role of TA in various conditions. J. Clin. Apheresis 31:516–522, 2016. © 2015 Wiley Periodicals, Inc.
Immunoadsorption therapy for dilated cardiomyopathy using tryptophan column—A prospective, multicenter, randomized, within‐patient and parallel‐group comparative study to evaluate efficacy and safety
Authors: Yoshikawa Tsutomu , Baba Akiyasu , Akaishi Makoto , Wakabayashi Yasuhisa , Monkawa Toshiaki , Kitakaze Masafumi , Izumi Tohru , Tomoike Hitonobu
Published: January 2016

Over the past few decades, several cardiac autoantibodies have been reported in sera from patients with dilated cardiomyopathy (DCM). Immunoadsorption (IA) therapy is one of the therapeutic tools to remove such autoantibodies. The objective of this study was to investigate functional effects of IA therapy using a tryptophan column in severe DCM patients. Of 49 patients enrolled, 44 were randomized from 10 sites in Japan. IA therapy was conducted in 40 patients with DCM (refractory to standard therapy for heart failure, New York Heart Association [NYHA] class III/IV, left ventricular ejection fraction [LVEF] <30%). Mean echocardiographic LVEF was significantly improved (23.8 ± 1.3% to 25.9 ± 1.3%, P = 0.0015). However, mean radionuclide LVEF over 3 months of IA therapy was not significantly improved (20.8 ± 1.1% to 21.9 ± 1%, P = 0.0605). The cardiothoracic ratio was also significantly decreased (P = 0.0010). NYHA functional class (P < 0.0001), subjective symptoms assessed by a quality of life questionnaire (P = 0.0022), maximum oxygen consumption (P = 0.0074), and 6‐minute walk distance (P = 0.0050) were improved after IA therapy. Subgroup analysis revealed improvement of echocardiographic LVEF in patients with higher baseline autoantibody scores but not in those with lower scores. IA therapy improved subjective symptoms and exercise capacity in patients with refractory heart failure resulting from DCM. Favorable effect on cardiac function was noted in patients with higher autoantibody scores. J. Clin. Apheresis 31:535–544, 2016. © 2015 Wiley Periodicals, Inc.
MicroRNA Expression Signatures During Malignant Progression From Barrett's Esophagus
Authors: Bansal Ajay , Gupta Vijayalaxmi , Wang Kenneth
Published: January 2016

The rapid increase and poor survival of esophageal adenocarcinoma (EAC) have led to significant efforts to promote early detection. Given that the premalignant lesion of Barrett's esophagus (BE) is the major known risk factor for EAC, multiple investigators have studied biomarker signatures that can predict malignant progression of BE to EAC. MicroRNAs, a novel class of gene regulators, are small non‐coding RNAs and have been associated with carcinogenesis. MicroRNAs are ideal biomarkers because of their remarkable stability in fixed tissues, a common method for collection of clinical specimens, and in blood either within exosomes or as microRNA‐protein complexes. Multiple studies show potential of microRNAs as tissue and blood biomarkers for diagnosis and prognosis of EAC but the results need confirmation in prospective studies. Although head‐to‐head comparisons are lacking, microRNA panels require less genes than messenger RNA panels for diagnosis of EAC in BE. MicroRNA diagnostic panels will need to be compared for accuracy against global measures of genome instability that were recently shown to be good predictors of progression but require sophisticated analytic techniques. Early studies on blood microRNA panels are promising but have found microRNA markers to be inconsistent among studies. MicroRNA expression in blood is different between various microRNA sub‐compartments such as exosomes and microRNA‐protein complexes and could affect blood microRNA measurements. Further standardization is needed to yield consistent results. We have summarized the current understanding of the tissue and blood microRNA signatures that may predict the development and progression of EAC. J. Cell. Biochem. 117: 1288–1295, 2016. © 2016 Wiley Periodicals, Inc.
Wave‐function frozen‐density embedding: Approximate analytical nuclear ground‐state gradients
Authors: Heuser Johannes , Höfener Sebastian
Published: January 2016

We report the derivation of approximate analytical nuclear ground‐state uncoupled frozen density embedding (FDEu) gradients for the resolution of identity (RI) variant of the second‐order approximate coupled cluster singles and doubles (RICC2) as well as density functional theory (DFT), and an efficient implementation thereof in the KOALA program. In order to guarantee a computationally efficient treatment, those gradient terms are neglected which would require the exchange of orbital information. This approach allows for geometry optimizations of single molecules surrounded by numerous molecules with fixed nuclei at RICC2‐in‐RICC2, RICC2‐in‐DFT, and DFT‐in‐DFT FDE level of theory using a dispersion correction, required due to the DFT‐based treatment of the interaction in FDE theory. Accuracy and applicability are assessed by the example of two case studies: (a) the Watson‐Crick pair adenine‐thymine, for which the optimized structures exhibit a maximum error of about 0.08 Å for our best scheme compared to supermolecular reference calculations, (b) carbon monoxide on a magnesium oxide surface model, for which the error amount up to 0.1 Å for our best scheme. Efficiency is demonstrated by successively including environment molecules and comparing to an optimized conventional supermolecular implementation, showing that the method is able to outperform conventional RICC2 schemes already with a rather small number of environment molecules, gaining significant speed up in computation time. © 2016 Wiley Periodicals, Inc.
Analysis of infectious complications and timing for emergency liver transplantation in autoimmune acute liver failure
Authors: Fujiwara Keiichi , Yasui Shin , Yonemitsu Yutaka , Arai Makoto , Kanda Tatsuo , Fukuda Yoshihiro , Nakano Masayuki , Oda Shigeto , Yokosuka Osamu
Published: January 2016

Background

Autoimmune hepatitis (AIH) is one of major etiologies of acute liver failure (ALF), and the survival rate without liver transplantation (LT) of patients with fulminant AIH is especially poor worldwide. We investigated the clinicopathological features of infectious complications in autoimmune ALF retrospectively and tried to determine when to continue corticosteroid (CS) treatment or abandon it for LT.

Methods

Twenty patients with autoimmune ALF, comprising five severe hepatitis, 13 fulminant hepatitis and two late onset hepatic failure, were analyzed.

Results

Corticosteroids were administered to 19 patients. Seventeen infectious complications were observed in 12 patients. The median (range) duration between the introduction of CS and onset of infection was 15 (10–41) days. There were no significant differences in clinicobiochemical features between patients with and without infection. Of 20 patients, eight (40%) recovered without LT, four (20%) received LT and eight (40%) died without LT. Dead or transplanted patients had more advanced liver failure on admission than recovered ones (P < 0.01).

Conclusions

Two‐week after the introduction of CS is a critical point for avoiding infectious complications. Therefore, we should have evaluated efficacy of CS and performed LT by then at the latest in case of failure to improve.
Noninvasive measurement of renal oxygen extraction fraction under the influence of respiratory challenge
Authors: Wang Chengyan , Zhang Rui , Wang Rui , Jiang Li , Zhang Xiaodong , Wang He , Zhao Kai , Jin Lixin , Zhang Jue , Wang Xiaoying , Fang Jing
Published: January 2016

Purpose

To demonstrate the feasibility of using a susceptibility‐based magnetic resonance imaging (MRI) technique for measuring renal oxygen extraction fraction (OEF) changes under the influence of carbogen (97% O2, 3% CO2) breathing.

Materials and Methods

Eight New Zealand White rabbits were included in this study with local animal care committee approval. For OEF measurement, an asymmetric spin echo (ASE) sequence was used to acquire source images and a susceptibility model was utilized for OEF estimation at 3.0T. Within‐session and between‐day tests were conducted to evaluate the reproducibility of this OEF measurement. OEF changes were measured under respiratory challenge with alternated air and carbogen (97% O2, 3% CO2) breathing. For comparison, blood samples were collected for the measurement of pO2.

Results

The within‐session coefficients of variation (CVs) of renal OEF measurements were 6.62% in cortex and 5.92% in medulla, while between‐day CVs were 7.52% in cortex and 8.03% in medulla. Under carbogen breathing, renal OEFs decreased significantly from 0.32 ± 0.03 to 0.28 ± 0.02 (P < 0.01) in cortex, and from 0.34 ± 0.04 to 0.31 ± 0.03 (P < 0.01) in medulla. No statistical difference of relative OEF change was seen between cortex and medulla (P = 0.93). In addition, negative correlation between renal OEF and blood pO2 was found (r = 0.68 (P < 0.05) in cortex, and r = 0.64 (P < 0.05) in medulla).

Conclusion

This study demonstrates the feasibility of using a susceptibility‐based OEF measurement method for the evaluation of renal oxygenation changes induced by carbogen breathing. J. Magn. Reson. Imaging 2016;44:230–237.
Diagnostic performance of MRI for prediction of candidates for local excision of rectal cancer (ypT0‐1N0) after neoadjuvant chemoradiation therapy
Authors: Kim Jun Gon , Song Kyoung Doo , Kim Seong Hyun , Kim Hee Cheol , Huh Jung Wook
Published: January 2016

Purpose

To evaluate the diagnostic performance of rectal MRI in predicting candidates for local excision (LE; ypT0‐1N0) after neoadjuvant chemoradiation therapy (CRT) in patients with rectal cancer.

Materials and Methods

The institutional review board approved our retrospective study and waived informed consent. Inclusion criteria were as follows: patients with pathologically confirmed mid to lower rectal cancer (cT3NxM0 before neoadjuvant CRT) who underwent neoadjuvant CRT and had MRI performed at 3T before and after neoadjuvant CRT. A total of 168 patients met the study criteria between 2011 and 2012. Two observers independently assessed tumor and nodal stages on MR images obtained after neoadjuvant CRT. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy for identifying a candidate for LE (ypT0‐1N0) were calculated. Interobserver agreement was assessed with kappa value. Predictive factors for ypT0‐1N0 were evaluated by logistic regression models.

Results

MRI had relatively high accuracy, specificity, and NPV (85.9%, 93.8%, and 88.9% for observer 1 and 85.3%, 96.1%, and 86.6% for observer 2), moderate PPV (71.4% and 76.2%), and relatively low sensitivity (57.1% and 45.7%) for predicting ypT0‐1N0. The interobserver agreement was fair (kappa value = 0.593). Carcinoembryonic antigen levels after neoadjuvant CRT and the maximal extramural depth of tumor spread were significant predictors of ypT0‐1N0 (P = 0.037 and 0.017, respectively).

Conclusion

MRI after neoadjuvant CRT can predict a candidate for LE (ypT0‐1N0) after neoadjuvant CRT with moderate PPV and relatively high NPV. J. Magn. Reson. Imaging 2016;44:471–477.
Computational postprocessing quantification of small bowel motility using magnetic resonance images in clinical practice: An initial experience
Authors: Åkerman André , Månsson Sven , Fork Frans‐Thomas , Leander Peter , Ekberg Olle , Taylor Stuart , Menys Alex , Ohlsson Bodil
Published: January 2016

Purpose

To study the feasibility and to gauge the potential clinical impact of quantifying small bowel motility using magnetic resonance imaging (MRI) in a larger population with a spectra of gastrointestinal conditions with impaired small bowel motility.

Materials and Methods

Data were gathered retrospectively from a cohort of 127 patients undergoing MR enterography (1.5 Tesla) in 2011. Cine motility sequences were processed with validated motility analysis software and a parametric motility map was generated. Regions of interests were drawn in the jejunum, ileum, and terminal ileum, and Jacobian standard deviation mean motility index' score (MIS) was calculated. Patients were divided into Crohn's disease (CD), ulcerative colitis, irritable bowel syndrome, and healthy subjects.

Results

In CD, terminal ileum motility was lower in comparison to healthy subjects (mean difference: ‐0.1052 arbitrary units, 95% confidence interval: ‐0.1981–‐0.0122, P = 0.018). Subgrouping of CD showed that the difference was recognized in patients with disease limited to the small bowel (mean difference: ‐0.1440 arbitrary units, 95% confidence interval: −0.2491–‐0.0389, P = 0.002). Visible dysmotility of terminal ileum on MRI reflected a reduced MIS compared with normal motility (0.22 ± 0.09 and 0.33 ± 0.15 arbitrary units, respectively, P = 0.043). Motility correlated negatively between ileum and age (P = 0.021), and between terminal ileum and C‐reactive protein in ulcerative colitis (P = 0.031).

Conclusion

Motility quantitation revealed a significant difference in motility of terminal ileum in patients with small bowel CD compared with healthy subjects, concording with visible dysmotility and inflammatory changes. J. Magn. Reson. Imaging 2016;44:277–287.
A Visual Representation to Quantitate, Diagnose, and Improve Creativity in Insight Problem Solving
Authors: McCaffrey Tony
Published: January 2016

A new visual representation for insight problems permits 22 new quantitative measures; which leads to a detailed diagnosis of a person's (or team's) creative weaknesses; which then leads to prescribing targeted, effective counter‐techniques for each weakness. Currently, only two measures are consistently used for insight problem solving: the number of problems solved and the time to solve the problems. These coarse measurements do not reveal the intricate dynamics of solving insight problems. Furthermore, four commonly used creativity measures (i.e.,fluency,originality,flexibility, andelaboration) are often not applied to insight problems. This new visualization permits the easy application of all four creativity measures. I challenge creativity researchers to help determine which of the 22 proposed quantitative measures are the most diagnostic for insight problem solving in isolation and, in a weighted linear combination, which might yield an effective quotient (i.e., overall measure) of insight problem solving ability.