bluuebunny/crossref_metadata_2025 huggingface dataset:
Randomized clinical trial on the effect of coffee on postoperative ileus following elective colectomy
Authors: Müller S A , Rahbari N N , Schneider F , Warschkow R , Simon T , von Frankenberg M , Bork U , Weitz J , Schmied B M , Büchler M W
Published: September 2012

Background

Postoperative ileus is a common problem after abdominal surgery. It was postulated that coffee intake would decrease postoperative ileus after colectomy.

Methods

This was a multicentre parallel open-label randomized trial. Patients with malignant or benign disease undergoing elective open or laparoscopic colectomy were assigned randomly before surgery to receive either coffee or water after the procedure (100 ml three times daily). The primary endpoint was time to first bowel movement; secondary endpoints were time to first flatus, time to tolerance of solid food, length of hospital stay and perioperative morbidity.

Results

A total of 80 patients were randomized, 40 to each group. One patient in the water arm was excluded owing to a change in surgical procedure. Patient characteristics were similar in both groups. In intention-to-treat analysis, the time to the first bowel movement was significantly shorter in the coffee arm than in the water arm (mean(s.d.) 60·4(21·3) versus 74·0(21·6) h; P = 0·006). The time to tolerance of solid food (49·2(21·3) versus 55·8(30·0) h; P = 0·276) and time to first flatus (40·6(16·1) versus 46·4(20·1) h; P = 0·214) showed a similar trend, but the differences were not significant. Length of hospital stay (10·8(4·4) versus 11·3(4·5) days; P = 0·497) and morbidity (8 of 40 versus 10 of 39 patients; P = 0·550) were comparable in the two groups.

Conclusion

Coffee consumption after colectomy was safe and was associated with a reduced time to first bowel action. Registration number: NCT01079442 (http://www.clinicaltrials.gov).
Illustrating the machinery of life: Viruses
Authors: Goodsell David S.
Published: September 2012

Data from electron microscopy, X‐ray crystallography, and biophysical analysis are used to create illustrations of viruses in their cellular context. This report describes the scientific data and artistic methods used to create three illustrations: a depiction of the poliovirus lifecycle, budding of influenza virus from a cell surface, and a mature HIV particle in blood serum.
Significance of lymphovascular space invasion in epithelial ovarian cancer
Authors: Matsuo Koji , Sheridan Todd B. , Yoshino Kiyoshi , Miyake Takahito , Hew Karina E. , Im Dwight D. , Rosenshein Neil B. , Mabuchi Seiji , Enomoto Takayuki , Kimura Tadashi , Sood Anil K. , Roman Lynda D.
Published: September 2012

While the prognostic significance of lymphovascular space invasion (LVSI) is well established in endometrial and cervical cancer, its role in ovarian cancer is not fully understood. First, a training cohort was conducted to explore whether the presence and quantity of LVSI within the ovarian tumor correlated with nodal metastasis and survival (n = 127). Next, the results of the training cohort were applied to a different study population (validation cohort, n = 93). In both cohorts, histopathology slides of epithelial ovarian cancer cases that underwent primary cytoreductive surgery including pelvic and/or aortic lymphadenectomy were examined. In a post hoc analysis, the significance of LVSI was evaluated in apparent stage I cases (n = 53). In the training cohort, the majority of patients had advanced‐stage disease (82.7%). LVSI was observed in 79.5% of cases, and nodal metastasis was the strongest variable associated with the presence of LVSI (odds ratio [OR]: 7.99, 95% confidence interval [CI]: 1.98–32.1, P = 0.003) in multivariate analysis. The presence of LVSI correlated with a worsened progression‐free survival on multivariate analysis (hazard ratio [HR]: 2.06, 95% CI: 1.01–4.24, P = 0.048). The significance of the presence of LVSI was reproduced in the validation cohort (majority, early stage 61.3%). In apparent stage I cases, the presence of LVSI was associated with a high negative predictive value for nodal metastasis (100%, likelihood ratio, P = 0.034) and with worsened progression‐free survival (HR: 5.16, 95% CI: 1.00–26.6, P = 0.028). The presence of LVSI is an independent predictive indicator of nodal metastasis and is associated with worse clinical outcome of patients with epithelial ovarian cancer.
Expression of RET finger protein predicts chemoresistance in epithelial ovarian cancer
Authors: Horio Maiko , Kato Takuya , Mii Shinji , Enomoto Atsushi , Asai Masato , Asai Naoya , Murakumo Yoshiki , Shibata Kiyosumi , Kikkawa Fumitaka , Takahashi Masahide
Published: September 2012

Resistance to platinum‐ and taxane‐based chemotherapy is a major cause of treatment failure in ovarian cancer. Thus, it is necessary to develop a predictive marker and molecular target for overcoming drug resistance in ovarian cancer treatment. In a previous report, using an in vitro model, we found that the RET finger protein (RFP) (also known as tripartite motif‐containing protein 27, TRIM27) confers cancer cell resistance to anticancer drugs. However, the significance of RFP expression in cancer patients remains elusive. In this study, we showed that RFP was expressed in 62% of ovarian cancer patients and its positivity significantly correlated with drug resistance. Consistent with clinical data, depletion of RFP by RNA interference (RNAi) in ovarian cancer cell lines, SKOV3 and HEY, significantly increased carboplatin‐ or paclitaxel‐induced apoptosis and resulted in reduced anticancer drug resistance. In a nude mouse tumor xenograft model, inoculated RFP‐knockdown ovarian cancer cells exhibited lower carboplatin resistance than control cells. These findings suggest that RFP could be a predictive marker for chemoresistance in ovarian cancer patients and also a candidate for a molecular‐targeted agent.
A Multi‐Yolk–Shell Structured Nanocatalyst Containing Sub‐10 nm Pd Nanoparticles in Porous CeO2
Authors: Chen Cheng , Fang Xiaoliang , Wu Binghui , Huang Liujun , Zheng Nanfeng
Published: September 2012

The fabrication of catalytically stable nanocatalysts containing fine noble metal nanoparticles is an important research theme. We report a method for the synthesis of a hierarchically structured Pd@hm‐CeO2 multi‐yolk–shell nanocatalyst (h=hollow; m=mesoporous) containing sub‐10 nm Pd nanoparticles from pre‐made hydrophobic Pd nanoparticles. In the developed method, monodisperse hydrophobic Pd nanoparticles are first reacted with an iron oxide precursor iron(III) acetylacetonate to allow the deposition of iron oxide on their surface. In a Brij 56–water–cyclohexane reverse micelle system, the surface growth of iron oxide is found to mediate and, thus, facilitate the encapsulation of hydrophobic Pd nanoparticles in SiO2 to yield Pd‐Fe2O3@SiO2 nanoparticles in a high concentration. After removal of Fe2O3 by acid, the obtained Pd@SiO2 core–shell particles are reacted solvothermally with Ce(NO3)3 in an ethylene glycol–water–acetic acid mixture to produce multi‐core–shell Pd@SiO2@m‐CeO2 nanospheres. In each multi‐core–shell Pd@SiO2@m‐CeO2 nanosphere, several Pd@SiO2 particles are separately embedded in mesoporous CeO2. After selective removal of silica by NaOH, Pd@SiO2@m‐CeO2 nanospheres are transformed into the multi‐yolk–shell Pd@hm‐CeO2 nanocatalyst. Even with a low Pd loading at 0.4 wt %, the as‐prepared multi‐yolk–shell Pd@hm‐CeO2 nanocatalyst displays high catalytic activity in CO oxidation with 100 % CO conversion at 110 °C. In comparison, under the same catalytic conditions, the same amount of the same‐sized Pd nanoparticles supported on SiO2 achieves 100 % CO conversion at 180 °C. More importantly, the multi‐yolk–shell structure of the Pd@hm‐CeO2 nanocatalyst significantly enhances the stability of the catalyst. No loss in catalytic activity was observed on the Pd@hm‐CeO2 nanocatalyst treated at 550 °C for six hours. The Pd@hm‐CeO2 nanocatalyst also exhibited excellent catalytic performance and stability in the aerobic selective oxidation of cinnamyl alcohol to cinnamaldehyde.
Supramolecular Assembly of Diplatinum Species through Weak PtII⋅⋅⋅PtII Intermolecular Interactions: A Combined Experimental and Computational Study
Authors: Pérez Paz Alejandro , Espinosa Leal Leonardo A. , Azani Mohammad‐Reza , Guijarro Alejandro , Sanz Miguel Pablo J. , Givaja Gonzalo , Castillo Oscar , Mas‐Ballesté Rubén , Zamora Félix , Rubio Angel
Published: September 2012

The present study elucidates the factors that govern the spontaneous self‐assembly of a family of dimetal [Pt2L4] (L=dithiocarboxylato ligand) complexes. Experimental data show that variables such as temperature, concentration, solvent and the nature of the ligand L have a critical effect on the reversible self‐assembly of supramolecular [Pt2L4]n entities. In solution, new UV/Vis spectroscopic features emerge at low temperatures and/or high concentrations, which are attributed to the formation of oligomeric [Pt2L4]n species. The description of intermolecular Pt⋅⋅⋅Pt interactions, the main driving force for the association, was addressed from a computational perspective. The contributions from intermolecular Pt⋅⋅⋅S and S⋅⋅⋅S interactions to these supramolecular assemblies were found to be repulsive. Experimental UV/Vis data have been interpreted by means of computational spectroscopy.
Parallelism, uniqueness, and large‐sample asymptotics for the Dantzig selector
Authors: Dicker Lee , Lin Xihong
Published: September 2012

The Dantzig selector (Candès & Tao, 2007) is a popular$\ell^{1}$‐regularization method for variable selection and estimation in linear regression. We present a very weak geometric condition on the observed predictors which is related to parallelism and, when satisfied, ensures the uniqueness of Dantzig selector estimators. The condition holds with probability 1, if the predictors are drawn from a continuous distribution. We discuss the necessity of this condition for uniqueness and also provide a closely related condition which ensures the uniqueness of lasso estimators (Tibshirani, 1996). Large sample asymptotics for the Dantzig selector, that is, almost sure convergence and the asymptotic distribution, follow directly from our uniqueness results and a continuity argument. The limiting distribution of the Dantzig selector is generally non‐normal. Though our asymptotic results require that the number of predictors is fixed (similar to Knight & Fu, 2000), our uniqueness results are valid for an arbitrary number of predictors and observations.The Canadian Journal of Statistics41: 23–35; 2013 © 2012 Statistical Society of Canada
Three‐level regular designs with general minimum lower‐order confounding
Authors: Li Zhiming , Zhang Tianfang , Zhang Runchu
Published: September 2012

In this paper, we extend the general minimum lower‐order confounding (GMC) criterion to the case of three‐level designs. First, we review the relationship between GMC and other criteria. Then we introduce an aliased component‐number pattern (ACNP) and a three‐level GMC criterion via the consideration of component effects, and obtain some results on the new criterion. All the 27‐run GMC designs, 81‐run GMC designs with factor numbers $n=5,\ldots,20$ and 243‐run GMC designs with resolution $IV$ or higher are tabulated. The Canadian Journal of Statistics 41: 192–210; 2013 © 2012 Statistical Society of Canada
Fgf10 expression patterns in the developing chick inner ear
Authors: Sánchez‐Guardado Luis Óscar , Puelles Luis , Hidalgo‐Sánchez Matías
Published: September 2012

The inner ear is a complex three‐dimensional sensorial structure with auditory and vestibular functions. It originates from the otic placode, which invaginates, forming the otic vesicle; the latter gives rise to neurosensory and nonsensory elements of the adult membranous labyrinth. A hypothesis based on descriptive and experimental evidence suggests that the acquisition of discrete sensory patches during evolution of this primordium may be related to subdivision of an early pansensory domain. In order to gain insight into this developmental mechanism, we carried out a detailed analysis of the spatial and temporal expression pattern of the gene Fgf10, by comparing different markers of otic patterning and hair cell differentiation. Fgf10 expression labels a sensory‐competent domain included in a Serrate‐positive territory from which most of the sensory epithelia arise. Our data show that Fgf10 transcripts are present initially in a narrow ventromedial band of the rudimentary otocyst, extending between its rostral and caudal poles. During development, this Fgf10‐expressing area splits repetitively into several separate subareas, creating six of the eight sensory organs present in birds. Only the lateral crista and the macula neglecta were initially Fgf10 negative, although they activated Fgf10 expression after their specification as sensory elements. These results allowed us to determine a timetable of sensory specification in the developing chick inner ear. The comparison of the expression pattern of Fgf10 with those of other markers of sensory differentiation contributes to our understanding of the mechanism by which vertebrate inner ear prosensory domains have arisen during evolution. J. Comp. Neurol. 521:1136–1164, 2013. © 2012 Wiley Periodicals, Inc.
The cellular and synaptic location of activated TrkB in mouse hippocampus during limbic epileptogenesis
Authors: Helgager Jeffrey , Liu Gumei , McNamara James O.
Published: September 2012

Understanding the mechanisms of limbic epileptogenesis in cellular and molecular terms may provide novel therapeutic targets for its prevention. The neurotrophin receptor tropomyosin‐related kinase B (TrkB) is thought to be critical for limbic epileptogenesis. Enhanced activation of TrkB, revealed by immunodetection of enhanced phosphorylated TrkB (pTrkB), a surrogate measure of its activation, has been identified within the hippocampus in multiple animal models. Knowledge of the cellular locale of activated TrkB is necessary to elucidate its functional consequences. Using an antibody selective to pTrkB in conjunction with confocal microscopy and cellular markers, we determined the cellular and subcellular locale of enhanced pTrkB induced by status epilepticus (SE) evoked by infusion of kainic acid into the amygdala of adult mice. SE induced enhanced pTrkB immunoreactivity in two distinct populations of principal neurons within the hippocampus—the dentate granule cells and CA1 pyramidal cells. Enhanced immunoreactivity within granule cells was found within mossy fiber axons and giant synaptic boutons. By contrast, enhanced immunoreactivity was found within apical dendritic shafts and spines of CA1 pyramidal cells. A common feature of this enhanced pTrkB at these cellular locales is its localization to excitatory synapses between excitatory neurons, presynaptically in the granule cells and postsynaptically in CA1 pyramidal cells. Long‐term potentiation (LTP) is one cellular consequence of TrkB activation at these excitatory synapses that may promote epileptogenesis. J. Comp. Neurol. 521:499–521, 2013. © 2012 Wiley Periodicals, Inc.
Genetic labeling of steroidogenic factor‐1 (SF‐1) neurons in mice reveals ventromedial nucleus of the hypothalamus (VMH) circuitry beginning at neurogenesis and development of a separate non‐SF‐1 neuronal cluster in the ventrolateral VMH
Authors: Cheung Clement C. , Kurrasch Deborah M. , Liang Jenna K. , Ingraham Holly A.
Published: September 2012

The ventromedial nucleus of the hypothalamus (VMH) influences a wide variety of physiological responses. Here, using two distinct but complementary genetic tracing approaches in mice, we describe the development of VMH efferent projections, as marked by steroidogenic factor‐1 (SF‐1; NR5A1). SF‐1 neurons were visualized by Tau‐green fluorescent protein (GFP) expressed from the endogenous Sf‐1 locus (Sf‐1TauGFP) or by crossing the transgenic Sf1:Cre driver to a GFP reporter strain (Z/EGSf1:Cre). Strikingly, VMH projections were visible early, at embryonic (E) 10.5, when few postmitotic SF1 neurons have been born, suggesting that formation of VMH circuitry begins at the onset of neurogenesis. At E14.5, comparison of these two reporter lines revealed that SF1‐positive neurons in the ventrolateral VMH (VMHvl) persist in Z/EGSf1:Cre embryos but are virtually absent in Sf‐1TauGFP. Therefore, although the entire VMH including the VMHvl shares a common lineage, the VMHvl further differentiates into a neuronal cluster devoid of SF‐1. At birth, extensive VMH projections to broad regions of the brain were observed in both mouse reporter lines, matching well with those previously discovered by injection of axonal anterograde tracers in adult rats. In summary, our genetic tracing studies show that VMH efferent projections are highly conserved in rodents and are established far earlier than previously appreciated. Moreover, our results imply that neurons in the VMHvl adopt a distinct fate early in development, which might underlie the unique physiological functions associated with this VMH subregion. J. Comp. Neurol., 521:1268–1288, 2013. © 2012 Wiley Periodicals, Inc.
Novel objective classification of reactive microglia following hypoglossal axotomy using hierarchical cluster analysis
Authors: Yamada Jun , Jinno Shozo
Published: September 2012

A total of 136 microglia were intracellularly labeled and their morphological features were evaluated by 3D morphometric measurement. According to hierarchical cluster analysis, microglia were objectively categorized into four groups termed types I–IV. The validity of this classification was confirmed by principal component analysis and linear discriminant analysis. Type I microglia were found in sham‐operated mice and in mice sacrificed 28 days (D28) after axotomy. The appearance of type I cells was similar to so‐called ramified microglia in a resting state. Type II microglia were mainly seen in D14 mice, which exhibited small cell bodies with thin and short processes. Interestingly, none of the already‐known morphological types of microglia seemed to be comparable to type II cells. We thus named type II microglia “small ramified” cells. Types III and IV microglia were mainly seen in D3 and D7 mice and their appearances were similar to hypertrophied and bushy cells, respectively. Proliferating cell nuclear antigen (PCNA), a mitosis marker, was almost exclusively expressed in D3 mice. On the other hand, voltage‐dependent potassium channels (Kv1.3/1.5), neurotoxicity‐related molecules, were most highly expressed in D14 mice. Increased expression of Kv1.3/1.5 in D14 mice was suppressed by minocycline treatment. These findings indicate that type II and III microglia may be involved in neurotoxicity and mitosis, respectively. Type IV microglial cells are assumed to be in the process of losing mitotic activity and gaining neurotoxicity. Our data also suggest that type II microglia can be a potential therapeutic target against neurodegenerative diseases. J. Comp. Neurol. 521:1184–1201, 2013. © 2012 Wiley Periodicals, Inc.
Synthesis and Applications of Graphene‐Based TiO2 Photocatalysts
Authors: Tan Lling‐Lling , Chai Siang‐Piao , Mohamed Abdul Rahman
Published: September 2012

Graphene is one of the most promising materials in the field of nanotechnology and has attracted a tremendous amount of research interest in recent years. Due to its large specific surface area, high thermal conductivity, and superior electron mobility, graphene is regarded as an extremely attractive component for the preparation of composite materials. At the same time, the use of photocatalysts, particularly TiO2, has also been widely studied for their potential in addressing various energy and environmental‐related issues. However, bare TiO2 suffers from low efficiency and a narrow light‐response range. Therefore, the combination of graphene and TiO2 is currently one of the most active interdisciplinary research areas and demonstrations of photocatalytic enhancement are abundant. This Review presents and discusses the current development of graphene‐based TiO2 photocatalysts. The theoretical framework of the composite, the synthetic strategies for the preparation and modification of graphene‐based TiO2 photocatalysts, and applications of the composite are reviewed, with particular attention on the photodegradation of pollutants and photocatalytic water splitting for hydrogen generation.
Inter‐laboratory assessment of flow cytometric monocyte HLA‐DR expression in clinical samples
Authors: Demaret Julie , Walencik Alexandre , Jacob Marie‐Christine , Timsit Jean‐François , Venet Fabienne , Lepape Alain , Monneret Guillaume
Published: September 2012

Background:

Diminished expression of human leukocyte antigen DR on circulating monocytes (mHLA‐DR) is a reliable indicator of immunosuppression in critically ill patients, predictive of both adverse outcome and septic complications. The objective of the present work was to test, in an inter‐laboratory clinical study, a standardized protocol for mHLA‐DR measurement by flow cytometry.

Methods:

mHLA‐DR was assessed in fresh whole blood according to a standardized staining protocol. Cells were analyzed on different flow cytometers (FC500, Navios, FACS Canto II) in different laboratories (Lyon and Grenoble). Results were expressed as numbers of antibodies bound per cell (AB/C).

Results:

Correlations between results were excellent (Pearson and interclass correlation coefficients > 0.98). Coefficients of variations for intra‐assay precision ranged from 1.9 to 3.2%. Conclusion: The present report highlights the robustness of this standardized flow cytometric protocol for mHLA‐DR measurement in multicentric clinical studies. © 2012 International Clinical Cytometry Society
Cell‐specific insulin resistance: implications for atherosclerosis
Authors: Rajwani A. , Cubbon R. M. , Wheatcroft S. B.
Published: September 2012

Insulin resistance is increasingly acknowledged as an independent risk factor for cardiovascular disease. Despite this, our understanding of the cellular and molecular mechanisms that might account for this relationship remain incompletely understood. A key challenge has been in distinguishing between a ‘whole‐body’ milieu of inflammation and oxidative stress from the ramifications of cell‐specific resistance to insulin. Transgenic models have now begun to explore the cellular influences of insulin resistance on vascular biology, with novel implications for atherosclerosis across a range of cells including endothelial cells, endothelial progenitor cells, vascular smooth muscle cells, macrophages and fibroblasts. Emerging data from these models have also begun to challenge conventional dogma. In particular, the findings across various cell types are disparate with some even implying a protective influence on vascular biology. We now review these data, highlighting recent advances in our understanding of cellular resistance to insulin as well as those areas where there remains a paucity of data. Copyright © 2012 John Wiley & Sons, Ltd.
Direct analysis of cannabis samples by desorption atmospheric pressure photoionization‐mass spectrometry
Authors: Kauppila Tiina J. , Flink Anu , Laakkonen Ulla‐Maija , Aalberg Laura , Ketola Raimo A.
Published: September 2012

Fast analysis of cannabis samples without prior sample preparation or chromatography was performed using desorption atmospheric pressure photoionization‐mass spectrometry (DAPPI‐MS). The MS2 spectra of the molecular ions of tetrahydrocannabinol (THC) and cannabidiol (CBD) formed in DAPPI‐MS showed distinct product ions, unlike the protonated molecules formed with other ambient mass spectrometry techniques, making possible the reliable identification of THC from cannabis samples. Copyright © 2012 John Wiley & Sons, Ltd.
Detection of PPARδ agonists GW1516 and GW0742 and their metabolites in human urine
Authors: Sobolevsky Tim , Dikunets Marina , Sukhanova Irina , Virus Edward , Rodchenkov Grigory
Published: September 2012

Peroxisome proliferator‐activated receptor‐δ (PPARδ) agonists are the drug candidates with potential performance‐enhancing properties, and therefore their illegitimate use in sports should be controlled. To simulate the metabolism of PPARδ agonist GW0742, in vitro reactions were performed which demonstrated that the main metabolic pathway is oxidation of the acyclic divalent sulfur to give the respective sulfoxide and sulfone. After being characterized by liquid chromatography–mass spectrometry (LC‐MS), these metabolites were evaluated in urine samples collected after a controlled excretion study. For comparative purposes, GW1516 excretion study was also performed. It has been shown that GW1516 and GW0742 are best monitored as the sulfone metabolites which are detectable in urine using LC‐MS/MS based procedure up to 40 and 20 days after a single oral dose of 15 mg each, respectively. The unmetabolized compounds are measurable only for a short period of time and at low ng/ml level. The sulfoxide‐to‐sulfone ratio for both GW1516 and GW0742 changed irregularly in the range of 1:3 to 1:15 depending on time elapsed after administration with a tendency of increasing the ratio with time. The other important finding was that the abundance of GW0742 and its metabolites in urine is about ten times lower than in case of GW1516. Copyright© 2012 John Wiley & Sons, Ltd.
Determination of anti‐convulsant and life‐preserving capacities of three types of auto‐injector therapies against soman intoxication in rats
Authors: Myhrer Trond , Enger Siri , Aas Pål
Published: September 2012

More effective countermeasures against nerve‐agent poisoning are needed, because current ones do not protect sufficiently, particularly the central nervous system (CNS). The purpose of the present study was to make a comparison of the antidotal capabilities of atropine/obidoxime/diazepam (termed the obidoxime regimen), atropine/HI‐6 (1‐[([4‐(aminocarbonyl)pyridinio]methoxy)methyl]‐2‐[(hydroxyimino)methyl]pyridinium)/avizafone (termed the HI‐6 regimen), and scopolamine/HI‐6/physostigmine (termed the physostigmine regimen) against various doses of soman (2, 3, 4 x LD50). The results showed that each regimen administered twice (1 min and 5 min after exposure) effectively prevented or terminated epileptiform activity within 10 min. However, the regimens differed markedly in life‐saving properties with the physostigmine regimen ranking highest followed in descending order by the HI‐6 and obidoxime regimens. Pretreatment with pyridostigmine increased the potency of the HI‐6 regimen, but not the obidoxime regimen. The latter regimen administered thrice (1 min, 5 min, and 9 min after exposure) did not compensate for the insufficiency. In half of the rats that lived for 7 days, neuropathology was unexpectedly observed predominantly in the left hemisphere unrelated to whether they seized or not. Local glutamatergic excitotoxic activity may occur even if manifest toxic signs are absent. The physostigmine regimen has excellent antidotal capacity, but the very narrow therapeutic window (< 10 min) makes it unsuitable for use in the field. The HI‐6 regimen appears to constitute an efficacious therapy against lower doses of soman (2 and 3 x LD50). Copyright © 2012 John Wiley & Sons, Ltd.
ATP conditions intestinal epithelial cells to an inflammatory state that promotes components of DC maturation
Authors: Yao Yu , Levings Megan K. , Steiner Theodore S.
Published: September 2012

Intestinal epithelial cells (IECs) normally promote the development of gut resident tolerogenic dendritic cells (DCs) and regulatory T cells, but how this process is altered in inflammatory bowel disease is not well characterized. Recently, we published that the cell injury signal ATP modulates IEC chemokine responses to the TLR5 ligand flagellin and exacerbates colitis in the presence of flagellin. We hypothesized that ATP switches these IECs from tolerogenic to proinflammatory, enhancing DC activation and immune responses to commensal antigens. Here, we report that ATP enhanced murine IEC production of KC, IL‐6, TGF‐β, and thymic stromal lymphopoietin in response to TLR1/2 stimulation by Pam3CSK4 (PAM). Moreover, supernatants from IECs stimulated with ATP+PAM enhanced expression of CD80 on bone marrow derived dendritic cells, and increased their production of IL‐12, IL‐6, IL‐23, TGF‐β, and aldh1a2, suggesting a Th1/Th17 polarizing environment. DCs conditioned by stressed IECs stimulated an enhanced recall response to flagellin and supported the expansion of IFN‐γ+ and IL‐17+ memory T cells. Lastly, colonic administration of nonhydrolysable ATP increased production of IL‐6 and Cxcl1 (KC) by IECs. These findings indicate that ATP influences the response of IECs to TLR ligands and biases the maturation of DCs to become inflammatory.
Fabrication and characterization of nanopores with insulated transverse nanoelectrodes for DNA sensing in salt solution
Authors: Healy Ken , Ray Vishva , Willis Lauren J. , Peterman Neil , Bartel John , Drndić Marija
Published: September 2012

We report on the fabrication, simulation, and characterization of insulated nanoelectrodes aligned with nanopores in low‐capacitance silicon nitride membrane chips. We are exploring these devices for the transverse sensing of DNA molecules as they are electrophoretically driven through the nanopore in a linear fashion. While we are currently working with relatively large nanopores (6–12 nm in diameter) to demonstrate the transverse detection of DNA, our ultimate goal is to reduce the size sufficiently to resolve individual nucleotide bases, thus sequencing DNA as it passes through the pore. We present simulations and experiments that study the impact of insulating these electrodes, which is important to localize the sensing region. We test whether the presence of nanoelectrodes or insulation affects the stability of the ionic current flowing through the nanopore, or the characteristics of DNA translocation. Finally, we summarize the common device failures and challenges encountered during fabrication and experiments, explore the causes of these failures, and make suggestions on how to overcome them in the future.
EPCAM–A novel molecular target for the treatment of pediatric and adult germ cell tumors
Authors: Schönberger Stefan , Okpanyi Vera , Calaminus Gabriele , Heikaus Sebastian , Leuschner Ivo , Nicholson James C. , Stoecklein Nikolas H. , Schneider Dominik T. , Borkhardt Arndt
Published: September 2012

Germ cell tumors (GCTs) are thought to develop from totipotent primordial germ cells. Although the epithelial cell adhesion molecule (EPCAM) is expressed on embryonic stem cells as well as different tumor cells, it has not yet been extensively studied in GCTs. We analyzed EPCAM expression by quantitative RT‐PCR in 48 fresh‐frozen GCT specimens of different histology (10 mature teratoma, MT; 6 immature teratoma, IT; 7 dysgerminoma; 6 mixed malignant GCTs; 19 yolk sac tumor, YST) and in the GCT cell lines NCCIT, TE76.T, JAR and 2102Ep, and correlated its expression with AFP and hCG protein levels, histologic differentiation, and clinical follow‐up data. EPCAM protein was visualized by immunohistochemistry of selected corresponding paraffin embedded tumor tissues. EPCAM was expressed in malignant but not in benign GCTs irrespective of age, sex, site and clinical stage of tumor (P = 0.001). In primary teratomas, EPCAM expression increased with their grade of immaturity (mean 2−ΔCt values: MT 0.23, IT 1.61, P = 0.007) and significantly correlated with serum AFP (P = 0.03) and hCG (P = 0.03) levels in malignant GCTs. Particularly high EPCAM levels were found in nonseminomatous GCTs such as YSTs (8.49) and choriocarcinoma (13.54). Immunohistochemical analysis verified gene expression data showing a distinct EPCAM staining in YST. Similarly in vitro, highest EPCAM expression was measured in GCT cell lines comprising yolk sac (2102Ep: 5.59) or choriocarcinoma (JAR: 10.65) components. This first comprehensive analysis of EPCAM in GCTs revealed high EPCAM expression in YSTs and choriocarcinomas. Thus, these nonseminomatous GCTs may be interesting targets for EPCAM immunotherapy, which has to be evaluated in further studies. © 2012 Wiley Periodicals, Inc.
The Adventures of Carbon Bond: Using a melodramatic game to explain CCS as a mitigation strategy for climate change
Authors: Feldpausch‐Parker Andrea M. , O'Byrne Megan , Endres Danielle , Peterson Tarla R.
Published: September 2012

Policy options for mitigating climate change have been severely limited in the USA by the clash of competing ideologies. People who oppose policies to mitigate climate change have successfully framed climate change as existing outside the realm of fact and empirical reality. Instead, opponents frame the issue as a melodramatic struggle between good and evil. While scientists and engineers tend to be uncomfortable with melodramatic framing, we argue that melodrama resonates with people. Constructing a different melodramatic frame can tap into people's tendency to conceptualize issues in terms of heroes and villains and assist in creating a shift in the political controversy from debating the factuality of climate change to a focus on mitigation. We developed an educational video game that uses this frame to teach students about climate change and carbon capture, and sequestration, to create an understanding of CO2 as the villain and humans as heroes through participation in mitigation strategies. The hero of this melodrama is aided by science and technology to mitigate anthropogenic climate change. We analyze The Adventures of Carbon Bond© as a medium for educating students about climate change and shifting framing. We begin with a discussion of melodrama and the rhetorical nature of video games. Then, through statistical analysis of surveys completed by students who played the game, we demonstrate that students experienced a knowledge increase as a result of game play. We conclude by discussing the implications of our findings for productively reframing climate change towards an emphasis on technological mitigation. © 2012 Society of Chemical Industry and John Wiley & Sons, Ltd
Neuromyelitis optica IgG does not alter aquaporin‐4 water permeability, plasma membrane M1/M23 isoform content, or supramolecular assembly
Authors: Rossi Andrea , Ratelade Julien , Papadopoulos Marios C. , Bennett Jeffrey L. , Verkman A. S.
Published: September 2012

Neuromyelitis optica (NMO) is thought to be caused by immunoglobulin G autoantibodies (NMO‐IgG) against astrocyte water channel aquaporin‐4 (AQP4). A recent study (Hinson et al. (2012) Proc Natl Acad Sci USA 109:1245‐1250) reported that NMO‐IgG inhibits AQP4 water permeability directly and causes rapid cellular internalization of the M1 but not M23 isoform of AQP4, resulting in AQP4 clustering, enhanced complement‐dependent cytotoxicity, and tissue swelling. Here, we report evidence challenging this proposed mechanism of NMO‐IgG‐mediated pathology. We measured osmotic water permeability by stopped‐flow light scattering on plasma membrane vesicles isolated from AQP4‐expressing CHO cells, an approach that can detect changes in water permeability as small as 5% and is not confounded by internalization effects. We found similar single‐molecule water permeability for M1‐AQP4 tetramers and M23‐AQP4 clusters (orthogonal arrays of particles, OAPs). Exposure of AQP4 to high concentrations of NMO‐IgG from six seropositive NMO patients, and to high‐affinity recombinant monoclonal NMO antibodies, did not reduce AQP4 water permeability. Also, NMO‐IgG did not reduce water permeability in AQP4‐reconstituted proteoliposomes. In transfected cells expressing M1‐ or M23‐AQP4 individually, NMO‐IgG caused more rapid internalization of M23‐ than M1‐AQP4. In cells coexpressing both isoforms, M1‐ and M23‐AQP4 comingled in OAPs that were internalized together in response to NMO‐IgG. Super‐resolution imaging and native gel electrophoresis showed that the size of AQP4 OAPs was not altered by NMO sera or recombinant NMO antibodies. We conclude that NMO‐IgG does not: (i) inhibit AQP4 water permeability, (ii) cause preferential internalization of M1‐AQP4, or (iii) cause intramembrane AQP4 clustering. © 2012 Wiley Periodicals, Inc.
Brain network of semantic integration in sentence reading: Insights from independent component analysis and graph theoretical analysis
Authors: Ye Zheng , Doñamayor Nuria , Münte Thomas F.
Published: September 2012

A set of cortical and sub‐cortical brain structures has been linked with sentence‐level semantic processes. However, it remains unclear how these brain regions are organized to support the semantic integration of a word into sentential context. To look into this issue, we conducted a functional magnetic resonance imaging (fMRI) study that required participants to silently read sentences with semantically congruent or incongruent endings and analyzed the network properties of the brain with two approaches, independent component analysis (ICA) and graph theoretical analysis (GTA). The GTA suggested that the whole‐brain network is topologically stable across conditions. The ICA revealed a network comprising the supplementary motor area (SMA), left inferior frontal gyrus, left middle temporal gyrus, left caudate nucleus, and left angular gyrus, which was modulated by the incongruity of sentence ending. Furthermore, the GTA specified that the connections between the left SMA and left caudate nucleus as well as that between the left caudate nucleus and right thalamus were stronger in response to incongruent vs. congruent endings. Hum Brain Mapp 35:367–376, 2014. © 2012 Wiley Periodicals, Inc.
Nonlocal regularization for active appearance model: Application to medial temporal lobe segmentation
Authors: Hu Shiyan , Coupé Pierrick , Pruessner Jens C. , Collins D. Louis
Published: September 2012

The human medial temporal lobe (MTL) is an important part of the limbic system, and its substructures play key roles in learning, memory, and neurodegeneration. The MTL includes the hippocampus (HC), amygdala (AG), parahippocampal cortex (PHC), entorhinal cortex, and perirhinal cortex—structures that are complex in shape and have low between‐structure intensity contrast, making them difficult to segment manually in magnetic resonance images. This article presents a new segmentation method that combines active appearance modeling and patch‐based local refinement to automatically segment specific substructures of the MTL including HC, AG, PHC, and entorhinal/perirhinal cortex from MRI data. Appearance modeling, relying on eigend‐ecomposition to analyze statistical variations in image intensity and shape information in study population, is used to capture global shape characteristics of each structure of interest with a generative model. Patch‐based local refinement, using nonlocal means to compare the image local intensity properties, is applied to locally refine the segmentation results along the structure borders to improve structure delimitation. In this manner, nonlocal regularization and global shape constraints could allow more accurate segmentations of structures. Validation experiments against manually defined labels demonstrate that this new segmentation method is computationally efficient, robust, and accurate. In a leave‐one‐out validation on 54 normal young adults, the method yielded a mean Dice κ of 0.87 for the HC, 0.81 for the AG, 0.73 for the anterior parts of the parahippocampal gyrus (entorhinal and perirhinal cortex), and 0.73 for the posterior parahippocampal gyrus. Hum Brain Mapp 35:377–395, 2014. © 2012 Wiley Periodicals, Inc.
Why is there a special issue on perirhinal cortex in a journal called hippocampus? The perirhinal cortex in historical perspective
Authors: Murray Elisabeth A. , Wise Steven P.
Published: September 2012

Despite its small size, the perirhinal cortex (PRh) plays a central role in understanding the cerebral cortex, vision, and memory; it figures in discussions of cognitive capacities as diverse as object perception, semantic knowledge, feelings of familiarity, and conscious recollection. Two conceptual constructs have encompassed PRh. The current orthodoxy incorporates PRh within the medial temporal lobe (MTL) as a memory area; an alternative considers PRh to be a sensory area with a role in both perception and memory. A historical perspective provides insight into both these ideas. PRh came to be included in the MTL because of two accidents of history. In evolutionary history, the hippocampus migrated from its ancestral situation as medial cortex into the temporal lobe; in the history of neuropsychology, a “memory system” that originally consisted of the amygdala and hippocampus came to include PRh. These two histories explain why a part of the sensory neocortex, PRh, entered into the conceptual construct called the MTL. They also explain why some experimental results seem to exclude a perceptual function for this sensory area, while others embrace perception. The exclusion of perceptual functions results from a history of categorizing tasks as perceptual or mnemonic, often on inadequate grounds. By exploring the role of PRh in encoding, representing, and retrieving stimulus information, it can be understood as a part of the sensory neocortex, one that has the same relationship with the hippocampus as do other parts of the neocortex that evolved at about the same time. © 2012 Wiley Periodicals, Inc.
The effects of combined perirhinal and postrhinal damage on complex discrimination tasks
Authors: Gastelum Emily D. , Guilhardi Paulo , Burwell Rebecca D.
Published: September 2012

Rats with combined lesions of the perirhinal (PER) and postrhinal (POR) cortices were trained on a complex discrimination in the simultaneous feature‐positive and feature‐negative discrimination task. In this task, a panel light (L) paired with an auditory stimulus determined whether a tone (T) or white noise (N) would be rewarded (+) or not rewarded (−). Thus, the light feature determined whether the target auditory stimuli were rewarded or not. In each session, trial types were LT+, T−, N+, and LN−. We had hypothesized that damage to the target regions would impair performance on this task. Acquisition was altered in the lesioned rats, but not in the predicted direction. Instead, lesioned rats exhibited significantly enhanced acquisition of the discrimination. Manipulation of intertrial intervals indicated that reduction of proactive interference did not explain the enhancement. Lesioned rats were not different from controls on a multiple‐cued interval timing task, providing evidence that the enhancement does not extend to all types of discriminations and is not due to a deficit in timing. Other research shows that rats with PER lesions are impaired on similar tasks, thus the enhancement is likely due to the effects of POR damage. Normally in this task, context is thought to accrue inhibitory control over other cues. Without this inhibitory control, animals might be expected to learn the task more efficiently. Our conclusion is that deficits in processing contextual information underlie the enhanced acquisition observed in rats with combined PER and POR damage on this complex discrimination task. © 2012 Wiley Periodicals, Inc.
The perirhinal cortex modulates V2 activity in response to the agreement between part familiarity and configuration familiarity
Authors: Peterson Mary A. , Cacciamani Laura , Barense Morgan D. , Scalf Paige E.
Published: September 2012

Research has demonstrated that the perirhinal cortex (PRC) represents complex object‐level feature configurations, and participates in familiarity versus novelty discrimination. Barense et al. [(in press) Cerebral Cortex, 22:11, doi:10.1093/cercor/bhr347] postulated that, in addition, the PRC modulates part familiarity responses in lower‐level visual areas. We used fMRI to measure activation in the PRC and V2 in response to silhouettes presented peripherally while participants maintained central fixation and performed an object recognition task. There were three types of silhouettes: Familiar Configurations portrayed real‐world objects; Part‐Rearranged Novel Configurations created by spatially rearranging the parts of the familiar configurations; and Control Novel Configurations in which both the configuration and the ensemble of parts comprising it were novel. For right visual field (RVF) presentation, BOLD responses revealed a significant linear trend in bilateral BA 35 of the PRC (highest activation for Familiar Configurations, lowest for Part‐Rearranged Novel Configurations, with Control Novel Configurations in between). For left visual field (LVF) presentation, a significant linear trend was found in a different area (bilateral BA 38, temporal pole) in the opposite direction (Part‐Rearranged Novel Configurations highest, Familiar Configurations lowest). These data confirm that the PRC is sensitive to the agreement in familiarity between the configuration level and the part level. As predicted, V2 activation mimicked that of the PRC: for RVF presentation, activity in V2 was significantly higher in the left hemisphere for Familiar Configurations than for Part‐Rearranged Novel Configurations, and for LVF presentation, the opposite effect was found in right hemisphere V2. We attribute these patterns in V2 to feedback from the PRC because receptive fields in V2 encompass parts but not configurations. These results reveal two new aspects of PRC function: (1) it is sensitive to the congruency between the familiarity of object configurations and the parts comprising those configurations and (2) it likely modulates familiarity responses in visual area V2. © 2012 Wiley Periodicals, Inc.
Layer V perirhinal cortical ensemble activity during object exploration: A comparison between young and aged rats
Authors: Burke S.N. , Hartzell A.L. , Lister J.P. , Hoang L.T. , Barnes C.A.
Published: September 2012

Object recognition memory requires the perirhinal cortex (PRC) and this cognitive function declines during normal aging. Recent electrophysiological recordings from young rats have shown that neurons in Layer V of the PRC are activated by three‐dimensional objects. Thus, it is possible that age‐related object recognition deficits result from alterations in PRC neuron activity in older animals. To examine this, the present study used cellular compartment analysis of temporal activity by fluorescence in situ hybridization (catFISH) with confocal microscopy to monitor cellular distributions of activity‐induced Arc RNA in layer V of the PRC. Activity was monitored during two distinct epochs of object exploration. In one group of rats (6 young/6 aged) animals were placed in a familiar testing arena and allowed to explore five different three‐dimensional objects for two 5‐min sessions separated by a 20‐min rest (AA). The second group of animals (6 young/6 aged) also explored the same objects for two 5‐min sessions, but the environment was changed between the first and the second epoch (AB). Behavioral data showed that both age groups spent less time exploring objects during the second epoch, even when the environment changed, indicating successful recognition. Although the proportion of active neurons between epochs did not change in the AA group, in the AB group more neurons were active during epoch 2 of object exploration. This recruitment of neurons into the active neural ensemble could serve to signal that familiar stimuli are being encountered in a new context. When numbers of Arc positive neurons were compared between age groups, the old rats had significantly lower proportions of Arc‐positive PRC neurons in both the AA and AB behavioral conditions. These data support the hypothesis that age‐associated functional alterations in the PRC contribute to declines in stimulus recognition over the lifespan. © 2012 Wiley Periodicals, Inc.