bluuebunny/crossref_metadata_2025 huggingface dataset:
Gold(I)‐Catalyzed Enantioselective Desymmetrization of 1,3‐Diols through Intramolecular Hydroalkoxylation of Allenes
Authors: Zi Weiwei , Toste F. Dean
Published: September 2015

A gold(I)‐catalyzed enantioselective desymmetrization of 1,3‐diols was achieved by intramolecular hydroalkoxylation of allenes. The catalyst system 3‐F‐dppe(AuCl)2 /(R)‐C8‐TRIPAg proved to be specifically efficient to promote the desymmetrizing cyclization of 2‐aryl‐1,3‐diols, which have proven challenging substrates in previous reports. Multisubstituted tetrahydrofurans were prepared in good yield with good enantioselectivity and diastereoselectivity by this method.
A Mechanochemically Triggered “Click” Catalyst
Authors: Michael Philipp , Binder Wolfgang H.
Published: September 2015

“Click” chemistry represents one of the most powerful approaches for linking molecules in chemistry and materials science. Triggering this reaction by mechanical force would enable site‐ and stress‐specific “click” reactions—a hitherto unreported observation. We introduce the design and realization of a homogeneous Cu catalyst able to activate through mechanical force when attached to suitable polymer chains, acting as a lever to transmit the force to the central catalytic system. Activation of the subsequent copper‐catalyzed “click” reaction (CuAAC) is achieved either by ultrasonication or mechanical pressing of a polymeric material, using a fluorogenic dye to detect the activation of the catalyst. Based on an N‐heterocyclic copper(I) carbene with attached polymeric chains of different flexibility, the force is transmitted to the central catalyst, thereby activating a CuAAC in solution and in the solid state.
Styrene‐butadiene‐styrene copolymer compatibilized interfacial modified multiwalled carbon nanotubes with mechanical and piezoresistive properties
Authors: Wang Lun , Wang Zhe , Wang Yue , Wang Xue , Wang Hengwei , Lu Guoming , Zhao Dongyu , Li Zewen
Published: September 2015

In this study, styrene‐butadiene‐styrene tri‐block copolymer/multiwalled carbon nanotubes (SBS/MWNTs) were prepared by means of a solution blending method. To enhance the compatibility between SBS and MWNTs, the SBS grafted MWNTs (SBS‐g‐MWNTs) were used to replace MWNTs. The MWNTs were chemically hydroxylated by the dissolved KOH solution with ethanol as solvent and then reacted with 3‐Aminopropyltriethoxysilane (APTES) to functionalize them with amino groups (MWNT‐NH2). The SBS‐g‐MWNTs were finally obtained by the reaction of MWNT‐NH2 and maleic anhydride grafted SBS (MAH‐g‐SBS). The SBS‐g‐MWNTs were characterized by X‐ray photoelectron spectroscopy (XPS), Fourier transform‐infrared spectroscopy (FT‐IR), transmission electron microscopy (TEM), scanning electron microscope (SEM), and thermogravimetric analysis (TGA). The results showed that the SBS molecules were homogeneously bonded onto the surface of the MWNTs, leading to an improvement of the mechanical and electrical properties of SBS/SBS‐g‐MWNTs composites due to the excellent interfacial adhesion and dispersion of SBS‐g‐MWNTs in SBS. A series of continuous tests were carried out to explore the electrical‐mechanical properties of the SBS/SBS‐g‐MWNTs composites. We found out that, near the percolation threshold, the well‐dispersed SBS/SBS‐g‐MWNTs composites showed good piezoresistive characteristics and small mechanical destructions for the development of little deformation under vertical pressure. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 42945.
Robust Input Covariance Constraint Control for Uncertain Polytopic Systems
Authors: Al‐Jiboory Ali Khudhair , Zhu Guoming
Published: September 2015

In this paper, the robust input covariance constraint (ICC) control problem with polytopic uncertainty is solved using convex optimization with linear matrix inequality (LMI) approach. The ICC control problem is an optimal control problem that optimizes the output performance subjected to multiple constraints on the input covariance matrices. This control problem has significant practical implications when hard constraints need to be satisfied on control actuators. The contribution of this paper is the characterization of the control synthesis LMIs used to solve the robust ICC control problem for polytopic uncertain systems. Both continuous‐ and discrete‐time systems are considered. Parameter‐dependent and independent Lyapunov functions have been used for robust ICC controller synthesis. Numerical design examples are presented to illustrate the effectiveness of the proposed approach.
Palladium(II) Acetate Catalyzed Reductive Heck Reaction of Enones; A Practical Approach
Authors: Mannathan Subramaniyan , Raoufmoghaddam Saeed , Reek Joost N. H. , de Vries Johannes G. , Minnaard Adriaan J.
Published: September 2015

A surprisingly practical Pd(OAc)2 or Pd(TFA)2‐catalyzed reductive Heck reaction between aryl iodides and α,β‐unsaturated ketones is described using N,N‐diisopropylethylamine (DIPEA, Hünigs base) as the reductant. In general, 1 mol % of Pd(OAc)2 is sufficient to afford good yields using electron‐rich or halogen‐substituted aryl iodides. Electron‐deficient aryl iodides preferentially give homocoupling. Enones containing aryl or bulky substituents on the β‐carbon react smoothly, producing mainly reductive Heck product, whereas enones with alkyl substituents on the β‐carbon afford a mixture of reductive Heck and Heck product. Deuterium labeling experiments show that the reaction is a bona fide reductive Heck reaction and exclude a Heck reaction‐conjugate reduction cascade.
Has Afirma gene expression classifier testing refined the indeterminate thyroid category in cytology?
Authors: Yang Sung‐Eun , Sullivan Peggy S. , Zhang Jianhua , Govind Rekha , Levin Mary R. , Rao Jian‐Yu , Moatamed Neda A.
Published: September 2015

BACKGROUND

Thyroid fine‐needle aspiration (FNA) plays a pivotal role in the evaluation of thyroid nodules. Up to 30% of cases are diagnosed as indeterminate by FNA, including atypia of undetermined significance, follicular lesion of undetermined significance, suspicious for a follicular neoplasm, and follicular neoplasm, with approximately two‐thirds having a benign outcome. The gene expression classifier (GEC) test is a molecular test for cases with indeterminate cytology. The purpose of the current study was to examine the refining role of the GEC test within a single institution.

METHODS

Retrospective analysis of all thyroid FNAs during a 20‐month period after implementation of GEC was performed. Cases of indeterminate cytology with concomitant GEC testing were selected and divided further in 4 subgroups. Correlation with surgical follow‐up, when available, was performed. The results were compared with previously published data from the study institution before the implementation of GEC testing.

RESULTS

Among the 217 cases, there were 189 with indeterminate cytology, 42% of which were benign and 50% of which were suspicious by GEC. The excisional rate of atypia of undetermined significance‐follicular lesion of undetermined significance in the pre‐GEC category was 63%, which decreased to 35% in the post‐GEC category, whereas the malignancy rate in the excised thyroids increased from 35% in the pre‐GEC category to 47% in the post‐GEC category. Similar findings also were obtained for suspicious for a follicular neoplasm‐follicular neoplasm lesions.

CONCLUSIONS

The strength of the GEC test appears to lie in its ability to reclassify 42% of indeterminate cytology cases as benign, thereby decreasing the number of unnecessary surgical procedures. Cancer (Cancer Cytopathol) 2016;124:100–109. © 2015 American Cancer Society.
Yolk hormones influence in ovo chemosensory learning, growth, and feeding behavior in domestic chicks
Authors: Bertin Aline , Meurisse Maryse , Arnould Cécile , Leterrier Christine , Constantin Paul , Cornilleau Fabien , Vaudin Pascal , Burlot Thierry , Delaveau Joel , Rat Christophe , Calandreau Ludovic
Published: September 2015

In this study, we assessed whether prenatal exposure to elevated yolk steroid hormones can influence in ovo chemosensory learning and the behavior of domestic chicks. We simulated a maternal environmental challenge by experimentally enhancing yolk progesterone, testosterone, and estradiol concentrations in hen eggs prior to incubation. The embryos from these hormones‐treated eggs (HO) as well as sham embryos (O) that had received the vehicle‐only were exposed to the odor of fish oil (menhaden) between embryonic Days 11 and 20. An additional group of control embryos (C) was not exposed to the odor. All chicks were tested following hatching for their feeding preferences between foods that were or were not odorized with the menhaden odor. In the 3‐min choice tests, the behavior of O chicks differed significantly according to the type of food whereas C and HO chicks showed no preference between odorized and non‐odorized food. Our result suggests weaker response in HO chicks. In addition, HO chicks showed impaired growth and reduced intake of an unfamiliar food on the 24‐h time scale compared to controls. Our data suggest that embryonic exposure to increased yolk hormone levels can alter growth, chemosensory learning, and the development of feeding behaviors. © 2015 Wiley Periodicals, Inc. Dev Psychobiol 58: 185–197, 2016.
The developmental inter‐relationships between activity, novelty preferences, and delay discounting in male and female rats
Authors: Lukkes Jodi L. , Thompson Britta S. , Freund Nadja , Andersen Susan L.
Published: September 2015

Increased locomotion, novelty‐seeking, and impulsivity are risk factors associated with substance use. In this study, the inter‐relationships between activity, novelty preferences, and delay discounting, a measure of impulsivity, were examined across three stages: juvenile/early adolescence (postnatal Day [P] 15, 19, and 42 for activity, novelty, and impulsivity, respectively), adolescent/late adolescent (P28, 32, 73), and adult (P90, 94, 137) in male and female rats. Our estimates of impulsive choice, where animals were trained to criterion, revealed an age × sex interaction where early adolescent females had the lowest levels of impulsivity. The relationships of activity and novelty to impulsivity significantly changed across age within each sex. Early adolescent males with high activity, but low novelty preferences, were more impulsive; however, low activity and high novelty preferences were related to high impulsivity in adult males. Female activity gradually increased across age, but did not show a strong relationship with impulsivity. Novelty preferences are moderately related to impulsivity into adulthood in females. These data show that males and females have different developmental trajectories for these behaviors. Males show greater sensation‐seeking (e.g., activity) and risky behavior (e.g., novelty preferences) earlier in life, whereas these behaviors emerge during adolescence in females. © 2015 Wiley Periodicals, Inc. Dev Psychobiol 58: 231–242, 2016.
A novel marine mesocosm facility to study global warming, water quality, and ocean acidification
Authors: Duarte Gustavo , Calderon Emiliano N. , Pereira Cristiano M. , Marangoni Laura F. B. , Santos Henrique F. , Peixoto Raquel S. , Bianchini Adalto , Castro Clovis B.
Published: September 2015

We describe a completely randomizable flow‐through outdoor mesocosm for climate change and ecotoxicology studies that was built with inexpensive materials. The 16 raceway tanks allow up to 6× water renewal per hour, avoiding changes in natural abiotic seawater conditions. We use an open‐source hardware board (Arduino) that was adapted to control heaters and an innovative CO2 injection system. This system reduced seawater pH up to −0.9 units and increased temperature up to +6°C in three treatments and a control. Treatments can be continuously compared with the control and vary according to diel fluctuations, thus following the diel range observed in the sea. The mesocosm facility also includes an integrated secondary system of 48 aquaria for ecotoxicology studies. We validated the reproducibility and relevance of our experimental system by analyzing the variation of the total DNA of the microbial community extracted from corals in three elevated temperature scenarios during a 40‐day experiment. We also present data from temperature, acidification, and copper contamination trials, which allowed continuous, reliable, and consistent treatment manipulations.
IL‐18‐induced expression of high‐affinity IL‐2R on murine NK cells is essential for NK‐cell IFN‐γ production during murine Plasmodium yoelii infection
Authors: Stegmann Kerstin A. , De Souza J. Brian , Riley Eleanor M.
Published: September 2015

Early production of pro‐inflammatory cytokines, including IFN‐γ, is essential for control of blood‐stage malaria infections. We have shown that IFN‐γ production can be induced among human natural killer (NK) cells by coculture with Plasmodium falciparum infected erythrocytes, but the importance of this response is unclear. To further explore the role of NK cells during malaria infection, we have characterized the NK‐cell response of C57BL/6 mice during lethal (PyYM) or nonlethal (Py17XNL) P. yoelii infection. Ex vivo flow cytometry revealed that NK cells are activated within 24 h of Py17XNL blood‐stage infection, expressing CD25 and producing IFN‐γ; this response was blunted and delayed during PyYM infection. CD25 expression and IFN‐γ production were highly correlated, suggesting a causal relationship between the two responses. Subsequent in vitro experiments revealed that IL‐18 signaling is essential for induction of CD25 and synergizes with IL‐12 to enhance CD25 expression on splenic NK cells. In accordance with this, Py17XNL‐infected erythrocytes induced NK‐cell CD25 expression and IFN‐γ production in a manner that is completely IL‐18‐ and partially IL‐12‐dependent, and IFN‐γ production is enhanced by IL‐2. These data suggest that IL‐2 signaling via CD25 amplifies IL‐18‐ and IL‐12‐mediated NK‐cell activation during malaria infection.
FeII Carbonyl Complexes Featuring Small to Bulky PNP Pincer Ligands – Facile Substitution of κ2P,N‐Bound PNP Ligands by Carbon Monoxide
Authors: Glatz Mathias , Holzhacker Christian , Bichler Bernhard , Mastalir Matthias , Stöger Berthold , Mereiter Kurt , Weil Matthias , Veiros Luis F. , Mösch‐Zanetti Nadia C. , Kirchner Karl
Published: September 2015

Complexes trans‐ and cis‐[Fe(κ3P,N,P‐PNP)(CO)Cl2] complexes bearing sterically demanding to small PNP ligands based on the 2,6‐diaminopyridine scaffold are synthesized. The aromatic pyridine ring and the phosphine PR2 moieties are connected through NH, N‐alkyl, or N‐aryl linkers. For bulky PNP ligands, with the exception of the ligands with PtBu2 units, these complexes are obtained upon the treatment of [Fe(κ3P,N,P‐PNP)Cl2] with CO. With small PNP ligands, such complexes are not accessible directly owing to the formation of [Fe(κ3P,N,P‐PNP)(κ2P,N‐PNP)Cl]Cl. These complexes liberate the κ2‐P,N‐bound PNP ligand in the presence of CO to yield [Fe(κ3P,N,P‐PNP)(CO)Cl2] in yields of less than 50 %. High yields are achieved by reacting FeCl2 with PNP ligands under a CO atmosphere. For structural and reactivity comparisons, [Fe(κ3P,N,P‐PNP‐Ph)(κ2P,N‐PN‐Ph)Cl]+ was prepared, and this complex does not react with CO. In contrast to the reactions in solution, in the solid state, complexes [Fe(κ3P,N,P‐PNP)Cl2] with NH linkers are also converted quantitatively into trans‐ or cis‐[Fe(κ3P,N,P‐PNP)(CO)(Cl)2] upon treatment with CO, as indicated by a color change and by IR spectroscopy monitoring. Those with N‐alkyl and N‐aryl linkers did not react with CO. To rationalize why most [Fe(κ3P,N,P‐PNP)Cl2] complexes react readily with CO but those with tBu substituents do not, the additions of CO to [Fe(κ3P,N,P‐PNP‐iPr)Cl2] and [Fe(κ3P,N,P‐PNP‐tBu)Cl2] were investigated by DFT calculations.
Synthesis and Assessment of CO‐Release Capacity of Manganese Carbonyl Complexes Derived from Rigid α‐Diimine ­Ligands of Varied Complexity
Authors: Jimenez Jorge , Chakraborty Indranil , Mascharak Pradip K.
Published: September 2015

Four manganese carbonyl complexes of the type [MnBr(CO)3(NN)] (NN = α‐diimine ligands): namely [MnBr(CO)3(bpy)] (1), [MnBr(CO)3(phen)] (2), [MnBr(CO)3(dafo)] (3), and [MnBr(CO)3(pyzphen)] (4) (where bpy = bipyridine, phen = 1,10‐phenanthroline, dafo = 4,5‐diazafluoren‐9‐one, and pyzphen = pyrazino[2,3‐f][1,10]‐phenanthroline) have been synthesized and structurally characterized. These four complexes, each containing the fac‐[Mn(CO)3] motif, release CO upon illumination with low‐power visible and UV light. The CO release rates and the absorption maxima of the complexes are, however, very similar, despite the systematic increase in structural complexity in the rigid α‐diimine ligand frameworks. This contrasts strongly with manganese carbonyl complexes derived from α‐diimine ligands in which at least one of the imine functions is not part of a rigid ring system. The results of this study should provide help in the future design of ligand frameworks suitable for the syntheses of photoCORMs to deliver CO to biological targets under the control of light.
Total Synthesis and Structural Reassignment of the γ‐Lactone Polyketide from Diaporthe sp. SXZ‐19
Authors: Yadav Jhillu S. , Dutta Palash , Ganganna Bogonda , Srinivas Eedubilli
Published: September 2015

The first stereoselective total synthesis of the proposed structure of the γ‐lactone from Diaporthe sp. SXZ‐19 was achieved by utilizing a convergent pathway. The four stereogenic centers were formed by employing Brown's asymmetric alkoxyallylboration reaction, and a cross‐metathesis reaction was used to construct the trans double bond of the γ‐lactone side chain. This synthesis led to a revision of proposed structural assignment of the natural product.
Synthesis of Alkynyl‐Glycinols by Lewis Acid Catalyzed Propargylic Substitution of Bis‐Imidates
Authors: Sirotkina Jekaterina , Grigorjeva Liene , Jirgensons Aigars
Published: September 2015

Racemic and enantioenriched alkynyl‐glycinols can be synthesized by Lewis acid catalyzed cyclization reaction of bis‐trichloracetimidates derived from alkynyl‐glycols. The cyclization proceeds selectively to give 4‐alkynyl‐oxazolines as the propargylic substitution products. Enantioenriched bis‐imidates that contain an alkyl or trimethylsilyl substituent at the acetylene gave oxazolines with complete inversion of configuration. In turn, considerable racemization was observed in the cyclization of bis‐imidates that contain a phenyl substituent. The racemization for these substrates can be suppressed by introduction of the electronegative substituent at the phenyl ring. Oxazolines prepared by bis‐imidate cyclization reaction can be readily transformed to protected alkynyl‐glycol derivatives.
Reactions of Thioacetamide Derivatives with Sulfonyl Azides: An Approach to Active‐Methylene N‐Sulfonylacetamidines
Authors: Dianova Lidia , Berseneva Vera , Beryozkina Tetyana , Efimov Ilya , Kosterina Maria , Eltsov Oleg , Dehaen Wim , Bakulev Vasiliy
Published: September 2015

Reactions of functionalized [CN, CO2Et, C(O)NHR, C(S)NR1R2] derivatives of thiomalonic acid and 2‐arylthioacetamides with sulfonyl azides were shown to give active‐methylene N‐sulfonylamidines in 62–98 % yields. Various procedures for the reactions, including the use of pyridine, boiling ethanol, and water, or running the reactions in the absence of a base and solvent at 80 °C, were carried out and compared. The solvent‐free variant was the best in terms of yield, and also because it does not require the use of an excess of the toxic and hazardous azides. The reaction was shown to tolerate electron‐withdrawing substituents such as carbonyl, cyano, and aryl groups at the C‐2 position. The presence of alkyl and phenyl groups on the nitrogen atom of the thioacetamide fragment, and the presence of substituents on the sulfonyl group were also tolerated. Thus, an efficient solvent‐free, catalyst‐free, and base‐free synthetic approach for the synthesis of N‐sulfonylmalonacetamidines and 2‐arylacetamidines was found.
On the Transfer of Chirality, Thermodynamic Stability, and Folding Characteristics of Stereoisomeric Gated Baskets
Authors: Hu Lei , Polen Shane , Hardin Alex M. , Pratumyot Yaowalak , Hadad Christopher M. , Badjić Jovica D.
Published: September 2015

We have prepared and characterized chiral and gated baskets (P/M)‐2, each containing a twisted P or M platform and three amidopyridine gates at the rim. Racemic (P/M)‐2 was found (1H NMR and IR spectroscopy) to stay monomeric in CDCl3 at 298.0 K with the gates forming a seam of intramolecular N–H···N hydrogen bonds. In particular, the amidopyridine gates assume a unidirectional orientation, as directed by the twisted platform, that is, the P‐shaped cup sets the amidopyridine gates in a counterclockwise (–) orientation of intramolecular N–H···N hydrogen bonds (VT 1H/13C NMR and M06‐2X/6‐31G*). The folded form of spacious (355 Å3) and chiral (P/M)‐2 undergoes an unfolding process in the presence of the polar [D6]DMSO solvent; specifically, with around 25 vol.‐% of [D6]DMSO, the N–H···N hydrogen bonds at the rim are broken, thereby allowing a stochastic rotation of the amidopyridine gates about the rim. Interestingly, the thermal stability of folded (P/M)‐2 is good with only a small fraction of unfolded state(s) forming at 104 °C in o‐xylene.
Social cognition and the cerebellum: A meta‐analytic connectivity analysis
Authors: Van Overwalle Frank , D'aes Tine , Mariën Peter
Published: September 2015

This meta‐analytic connectivity modeling (MACM) study explores the functional connectivity of the cerebellum with the cerebrum in social cognitive processes. In a recent meta‐analysis, Van Overwalle, Baetens, Mariën, and Vandekerckhove () documented that the cerebellum is implicated in social processes of “body” reading (mirroring; e.g., understanding other persons' intentions from observing their movements) and “mind” reading (mentalizing, e.g., inferring other persons' beliefs, intentions or personality traits, reconstructing persons' past, future, or hypothetical events). In a recent functional connectivity study, Buckner et al. () offered a novel parcellation of cerebellar topography that substantially overlaps with the cerebellar meta‐analytic findings of Van Overwalle et al. (). This overlap suggests that the involvement of the cerebellum in social reasoning depends on its functional connectivity with the cerebrum. To test this hypothesis, we explored the meta‐analytic co‐activations as indices of functional connectivity between the cerebellum and the cerebrum during social cognition. The MACM results confirm substantial and distinct connectivity with respect to the functions of (a) action understanding (“body” reading) and (b) mentalizing (“mind” reading). The consistent and strong connectivity findings of this analysis suggest that cerebellar activity during social judgments reflects distinct mirroring and mentalizing functionality, and that these cerebellar functions are connected with corresponding functional networks in the cerebrum. Hum Brain Mapp 36:5137–5154, 2015. © 2015 Wiley Periodicals, Inc.
Development of hyperdynamic circulation and response to β‐blockers in compensated cirrhosis with portal hypertension
Authors: Villanueva Càndid , Albillos Agustín , Genescà Joan , Abraldes Juan G. , Calleja Jose L. , Aracil Carles , Bañares Rafael , Morillas Rosa , Poca María , Peñas Beatriz , Augustin Salvador , Garcia‐Pagan Joan Carles , Pavel Oana , Bosch Jaume
Published: September 2015

Nonselective β‐blockers are useful to prevent bleeding in patients with cirrhosis and large varices but not to prevent the development of varices in those with compensated cirrhosis and portal hypertension (PHT). This suggests that the evolutionary stage of PHT may influence the response to β‐blockers. To characterize the hemodynamic profile of each stage of PHT in compensated cirrhosis and the response to β‐blockers according to stage, we performed a prospective, multicenter (tertiary care setting), cross‐sectional study. Hepatic venous pressure gradient (HVPG) and systemic hemodynamic were measured in 273 patients with compensated cirrhosis before and after intravenous propranolol (0.15 mg/kg): 194 patients had an HVPG ≥10 mm Hg (clinically significant PHT [CSPH]), with either no varices (n = 80) or small varices (n = 114), and 79 had an HVPG >5 and <10 mm Hg (subclinical PHT). Patients with CSPH had higher liver stiffness (P < 0.001), worse Model for End‐Stage Liver Disease score (P < 0.001), more portosystemic collaterals (P = 0.01) and splenomegaly (P = 0.01) on ultrasound, and lower platelet count (P < 0.001) than those with subclinical PHT. Patients with CSPH had lower systemic vascular resistance (1336 ± 423 versus 1469 ± 335 dyne · s · cm‐5, P < 0.05) and higher cardiac index (3.3 ± 0.9 versus 2.8 ± 0.4 L/min/m2, P < 0.01). After propranolol, the HVPG decreased significantly in both groups, although the reduction was greater in those with CSPH (‐16 ± 12% versus ‐8 ± 9%, P < 0.01). The HVPG decreased ≥10% from baseline in 69% of patients with CSPH versus 35% with subclinical PHT (P < 0.001) and decreased ≥20% in 40% versus 13%, respectively (P = 0.001). Conclusion: Patients with subclinical PHT have less hyperdynamic circulation and significantly lower portal pressure reduction after acute β‐blockade than those with CSPH, suggesting that β‐blockers are more suitable to prevent decompensation of cirrhosis in patients with CSPH than in earlier stages. (Hepatology 2016;63:197–206)
LTP enhances synaptogenesis in the developing hippocampus
Authors: Watson Deborah J. , Ostroff Linnaea , Cao Guan , Parker Patrick H. , Smith Heather , Harris Kristen M.
Published: September 2015

In adult hippocampus, long‐term potentiation (LTP) produces synapse enlargement while preventing the formation of new small dendritic spines. Here, we tested how LTP affects structural synaptic plasticity in hippocampal area CA1 of Long‐Evans rats at postnatal day 15 (P15). P15 is an age of robust synaptogenesis when less than 35% of dendritic spines have formed. We hypothesized that LTP might therefore have a different effect on synapse structure than in adults. Theta‐burst stimulation (TBS) was used to induce LTP at one site and control stimulation was delivered at an independent site, both within s. radiatum of the same hippocampal slice. Slices were rapidly fixed at 5, 30, and 120 min after TBS, and processed for analysis by three‐dimensional reconstruction from serial section electron microscopy (3DEM). All findings were compared to hippocampus that was perfusion‐fixed (PF) in vivo at P15. Excitatory and inhibitory synapses on dendritic spines and shafts were distinguished from synaptic precursors, including filopodia and surface specializations. The potentiated response plateaued between 5 and 30 min and remained potentiated prior to fixation. TBS resulted in more small spines relative to PF by 30 min. This TBS‐related spine increase lasted 120 min, hence, there were substantially more small spines with LTP than in the control or PF conditions. In contrast, control test pulses resulted in spine loss relative to PF by 120 min, but not earlier. The findings provide accurate new measurements of spine and synapse densities and sizes. The added or lost spines had small synapses, took time to form or disappear, and did not result in elevated potentiation or depression at 120 min. Thus, at P15 the spines formed following TBS, or lost with control stimulation, appear to be functionally silent. With TBS, existing synapses were awakened and then new spines formed as potential substrates for subsequent plasticity. © 2015 The Authors Hippocampus Published by Wiley Periodicals, Inc.
Priming for novel object associations: Neural differences from object item priming and equivalent forms of recognition
Authors: Gomes Carlos Alexandre , Figueiredo Patrícia , Mayes Andrew
Published: September 2015

The neural substrates of associative and item priming and recognition were investigated in a functional magnetic resonance imaging study over two separate sessions. In the priming session, participants decided which object of a pair was bigger during both study and test phases. In the recognition session, participants saw different object pairs and performed the same size‐judgement task followed by an associative recognition memory task. Associative priming was accompanied by reduced activity in the right middle occipital gyrus as well as in bilateral hippocampus. Object item priming was accompanied by reduced activity in extensive priming‐related areas in the bilateral occipitotemporofrontal cortex, as well as in the perirhinal cortex, but not in the hippocampus. Associative recognition was characterized by activity increases in regions linked to recollection, such as the hippocampus, posterior cingulate cortex, anterior medial frontal gyrus and posterior parahippocampal cortex. Item object priming and recognition recruited broadly overlapping regions (e.g., bilateral middle occipital and prefrontal cortices, left fusiform gyrus), even though the BOLD response was in opposite directions. These regions along with the precuneus, where both item priming and recognition were accompanied by activation, have been found to respond to object familiarity. The minimal structural overlap between object associative priming and recollection‐based associative recognition suggests that they depend on largely different stimulus‐related information and that the different directions of the effects indicate distinct retrieval mechanisms. In contrast, item priming and familiarity‐based recognition seemed mainly based on common memory information, although the extent of common processing between priming and familiarity remains unclear. Further implications of these findings are discussed. © 2015 Wiley Periodicals, Inc.
Glacial and periglacial floodplain sediments regulate hydrologic transfer of reactive iron to a high arctic fjord
Authors: Hodson Andrew , Nowak Aga , Christiansen Hanne
Published: September 2015

The transport of reactive iron (i.e. colloidal and dissolved) by a glacier‐fed stream system draining a high relief periglacial landscape in the high Arctic archipelago of Svalbard is described. A negative, non‐linear relationship between discharge and iron concentration is found, indicative of increased iron acquisition along baseflow pathways. Because the glaciers are cold‐based and there are no intra‐ or sub‐permafrost groundwater springs, baseflow is principally supplied by the active layer and the colluvial and alluvial sediments in the lower valley. Collectively, these environments increase the flux of iron in the stream by 40% over a floodplain length of just 8 km, resulting in 6 kg Fe km−2a−1 of reactive iron export for a 20% glacierized watershed. We show that pyrite oxidation in shallow‐groundwater flowpaths of the floodplain is the most important source of reactive iron, although it is far less influential in the upper parts of the catchment where other sources are significant (including ironstone and secondary oxide coatings). Microbial catalysis of the pyrite oxidation occurs in the floodplain, enabling rapid, hyporheic water exchange to enhance the iron fluxes at high discharge and cause the non‐linear relationship between discharge and reactive iron concentrations. Furthermore, because the pyrite oxidation is tightly coupled to carbonate and silicate mineral weathering, other nutrients such as base cations and silica are also released to the stream system. Our work therefore shows that high Arctic floodplains should be regarded as critically important regulators of terrestrial nutrient fluxes to coastal ecosystems from glacial and periglacial sources. Copyright © 2015 John Wiley & Sons, Ltd.
Anticalins directed against the fibronectin extra domain B as diagnostic tracers for glioblastomas
Authors: Albrecht Valerie , Richter Antonia , Pfeiffer Sarah , Gebauer Michaela , Lindner Simon , Gieser Eugenie , Schüller Ulrich , Schichor Christian , Gildehaus Franz Josef , Bartenstein Peter , Tonn Jörg‐Christian , Skerra Arne , Glass Rainer
Published: September 2015

The standard of care for diagnosis and therapy monitoring of gliomas is magnetic resonance imaging (MRI), which however, provides only an indirect and incomplete representation of the tumor mass, offers limited information for patient stratification according to WHO‐grades and may insufficiently indicate tumor relapse after antiangiogenic therapy. Anticalins are alternative binding proteins obtained via combinatorial protein design from the human lipocalin scaffold that offer novel diagnostic reagents for histology and imaging applications. Here, the Anticalins N7A, N7E and N9B, which possess exquisite specificity and affinity for oncofetal fibronectin carrying the extra domain B (ED‐B), a well‐known proangiogenic extracellular matrix protein, were applied for immunohistochemical studies. When investigating ED‐B expression in biopsies from 41 patients with confirmed gliomas of WHO grades I to IV, or in non‐neoplastic brain samples, we found that Anticalins specifically detect ED‐B in primary glioblastoma multiforme (GBM; WHO IV) but not in tumors of lower histopathological grade or in tumor‐free brain. In primary GBM samples, ED‐B specific Anticalins locate to fibronectin‐rich perivascular areas that are associated with angiogenesis. Anticalins specifically detect ED‐B both in fixed tumor specimen and on vital cells, as evidenced by cytofluorometry. Beyond that, we labeled an Anticalin with the γ‐emitter 123I and demonstrated specific binding to GBM‐tissue samples using in vitro autoradiography. Overall, our data indicate that ED‐B specific Anticalins are useful tools for the diagnosis of primary GBM and related angiogenic sites, presenting them as promising tracers for molecular tumor imaging.
The influence of hormone therapies on type I and II endometrial cancer: A nationwide cohort study
Authors: Mørch Lina S. , Kjær Susanne K. , Keiding Niels , Løkkegaard Ellen , Lidegaard Øjvind
Published: September 2015

The influence of hormone therapy (HT) on risk for endometrial cancer is still casting which type of HT the clinicians recommend. It is unrevealed if HT has a differential influence on Type I versus Type II endometrial tumors, and little is known about the influence of, e.g., different routes of administration and about the influence of tibolone. We followed all Danish women aged 50–79 years without previous cancer or hysterectomy (n = 914,595) during 1995–2009. From the National Prescription Register, we computed HT exposures as time‐dependent covariates. Incident endometrial cancers (n = 6,202) were identified from the National Cancer Registry: 4,972 Type I tumors and 500 Type II tumors. Incidence rate ratios (RRs) and 95% confidence intervals (Cls) were estimated by Poisson regression. Compared with women never on HT, the RR of endometrial cancer was increased with conjugated estrogen: 4.27 (1.92–9.52), nonconjugated estrogen: 2.00 (1.87–2.13), long cycle combined therapy: 2.89 (2.27–3.67), cyclic combined therapy: 2.06 (1.88–2.27), tibolone 3.56 (2.94–4.32), transdermal estrogen: 2.77 (2.12–3.62) and vaginal estrogen: 1.96 (1.77–2.17), but not with continuous combined therapy: 1.02 (0.87–1.20). In contrast, the risk of Type II tumors appeared decreased with continuous combined therapy: 0.45 (0.20–1.01), and estrogen therapy implied a nonsignificantly altered risk of 1.43 (0.85–2.41). Our findings support that continuous combined therapy is risk free for Type I tumors, while all other hormone therapies increase risk. In contrast, Type II endometrial cancer was less convincingly associated with hormone use, and continuous combined therapy appeared to decrease the risk.
Copper‐transporting ATPases: The evolutionarily conserved machineries for balancing copper in living systems
Authors: Migocka Magdalena
Published: September 2015

Copper ATPases (Cu‐ATPases) are ubiquitous transmembrane proteins using energy from ATP to transport copper across different biological membranes of prokaryotic and eukaryotic cells. As they belong to the P‐ATPase family, Cu‐ATPases contain a characteristic catalytic domain with an evolutionarily conserved aspartate residue phosphorylated by ATP to form a phosphoenzyme intermediate, as well as transmembrane helices containing a cation‐binding cysteine‐proline‐cysteine/histidine/serine (CPx) motif for catalytic activation and cation translocation. In addition, most Cu‐ATPases possess the N‐terminal Cu‐binding CxxC motif required for regulation of enzyme activity. In cells, the Cu‐ATPases receive copper from soluble chaperones and maintain intracellular copper homeostasis by efflux of copper from the cell or transport of the metal into the intracellular compartments. In addition, copper pumps play an essential role in cuproprotein biosynthesis by the uptake of copper into the cell or delivery of the metal into the chloroplasts and thylakoid lumen or into the lumen of the secretory pathway, where the metal ion is incorporated into copper‐dependent enzymes. In the recent years, significant progress has been made toward understanding the function and regulation of Cu‐transporting ATPases in archaea, bacteria, yeast, humans, and plants, providing new insights into the specific physiological roles of these essential proteins in various organisms and revealing some conservative regulatory mechanisms of Cu‐ATPase activity. In this review, the structural, biochemical, and functional properties of Cu‐ATPases from phylogenetically different organisms are summarized and discussed, with particular attention given to the recent insights into the molecular biology of copper pumps in plants. © 2015 IUBMB Life, 67(10):737–745, 2015
Biocompatibility of common polyimides with human endothelial cells for a cardiovascular microsensor
Authors: Starr Peter , Agrawal C. Mauli , Bailey Steven
Published: September 2015

The cardiovasculature is an emerging niche for polyimide microdevices, yet the biocompatibility of polyimides with human endothelial cells has not been reported in the literature. In this study, we have evaluated an experimental polyimide‐based pressure sensor for biological safety to determine its suitability for intravascular operation by using an in vitro model of human endothelium, following ISO 10993‐5 protocols for extract tests and direct contact tests. First, SV‐HCEC cells were incubated with extracts derived from common microfabrication polyimides utilized in the transducer (PMDA‐ODA, BPDA‐PPD, and a proprietary thermoplastic adhesive), and then labeled with selective probes to evaluate the effect of the polyimides on mitochondria and cell viability. Flow cytometry analysis showed that incubation of SV‐HCECs with polyimide extracts resulted in no significant change in mitochondrial membrane potential (detected by JC‐1) or apoptotic (annexin V) and necrotic (propidium iodide) cell death, when compared to incubation with extracts of high‐density polyethylene (HDPE) and untreated cells used as negative controls. Second, primary human endothelial cells were incubated in direct contact with the completed sensor and then labeled with selective probes for live‐dead analysis (calcein‐AM, ethidium homodimer‐1). Endothelial cells showed no loss of viability when compared to negative controls. Combined, the studies show no significant change in early markers of stress or more strict markers of viability in endothelial cells treated with the polyimides tested. We conclude that these common microfabrication polyimides and the derived sensor are not cytotoxic to human endothelial cells, the primary cell type that cardiovascular sensors will contact in vivo. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 406–412, 2016.
Heterogeneity of biomaterial‐induced multinucleated giant cells: Possible importance for the regeneration process?
Authors: Barbeck Mike , Motta Antonella , Migliaresi Claudio , Sader Robert , Kirkpatrick Charles James , Ghanaati Shahram
Published: September 2015

Biomaterial‐associated multinucleated giant cells (BMGCs) have been found within the implantation beds of many different biomaterials. However, their exact differentiation and their involvement in the inflammatory and healing events of the foreign body response still remain mostly unclear. Silk fibroin (SF) scaffolds, which induces a tissue reaction involving both macrophages and BMGCs, was implanted in the subcutaneous connective tissue of four CD‐1 mice for 15 days using an established subcutaneous implantation model. Analysis of macrophage polarization and BMGCs was performed by immunohistochemcial detection of pro‐ (cyclooxygenase‐2 (COX‐2), C‐C chemokine receptor type 7 (CCR7), nuclear factor “kappa‐light‐chain‐enhancer” (NF‐κB)) and anti‐(heme oxygenase‐1 (HO‐1) and mannose receptor (MR, also known as CD206)). Furthermore, histochemical detection of tartrate‐resistant acid phosphatase (TRAP) was conducted to test its predictive efficiency for the pro‐inflammatory differentiation of cells. An established system for histomorphometrical analysis was used for counting of BMGCs expressing these molecules. The results show that BMGCs express both pro‐ and anti‐inflammatory molecules within the implantation beds of SF scaffolds in comparable numbers, while only statistically significantly lower numbers of TRAP‐positive BMGCs were measured in comparison to the BMGCs expressing the above‐mentioned molecules. As these data substantiate the heterogeneity of BMGCs, the question arises to what extent BMGCs can “support” the process of tissue regeneration. Furthermore, the data prompt the question to what extent TRAP‐expression within a biomaterial implantation bed can be seen as a predictive marker for an inflammatory condition, as in this study no obvious correlation between TRAP‐expression and other pro‐inflammatory markers could be observed. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 413–418, 2016.
Injectable hydrogel provides growth‐permissive environment for human nucleus pulposus cells
Authors: Priyadarshani Priyanka , Li Yongchao , Yang ShangYou , Yao Li
Published: September 2015

Degeneration of intervertebral discs (IVDs) results in an overall alteration of the biomechanics of the spinal column and becomes a major cause of low back pain. In this study, an injectable hydrogel composite is fabricated and characterized as a potential scaffold for the treatment of degenerated IVDs. Crosslinking of type II collagen‐hyaluronic acid (HA) hydrogel with 1‐ethyl‐3(3‐dimethyl aminopropyl) carbodiimide (EDC) increases the gel stability against collagenase digestion and reduces water uptake in comparison with non‐crosslinked gel. Cell viability assay exhibits the proliferation of human nucleus pulposus (HNP) cells in hydrogels. The cells in non‐crosslinked gel and the gel crosslinked with a low concentration of EDC (0.1 mM) show superior cell viability and morphology compared with cells in gels crosslinked with higher concentration of EDC. Quantitative PCR assay demonstrates the gene expression of extracellular matrix (ECM) by cells cultured in the gels. The expression of ECM genes by HNP cells in the gels demonstrated the phenotypic change of the cells. This study suggests that the type II collagen‐HA hydrogel and crosslinked hydrogel (0.1 mMEDC) are permissive matrix for the growth of HNP cells and can be potentially applied in NP repair. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 419–426, 2016.
The effect of noninvasive brain stimulation on neural connectivity in Tinnitus: A randomized trial
Authors: Roland Lauren T. , Peelle Jonathan E. , Kallogjeri Dorina , Nicklaus Joyce , Piccirillo Jay F.
Published: September 2015

Objectives/Hypothesis

To explore neural connectivity changes associated with repetitive transcranial magnetic stimulation (rTMS) to the temporoparietal junction for patients with bothersome tinnitus.

Study Design

Randomized, double‐blind, controlled clinical trial.

Methods

Thirty patients with subjective, nonpulsatile tinnitus for 6 months duration or longer and a score of 36 or greater on the Tinnitus Handicap Inventory completed the study. Participants were randomized to receive either sham or active treatment with rTMS to the temporoparietal junction for either 2 or 4 weeks of therapy. Participants underwent resting state functional connectivity magnetic resonance imaging before therapy and immediately following treatment. Functional connectivity changes between active and sham treatment groups were compared using regions of interest in auditory, default mode, ventral attention, and executive attention networks.

Results

Sixteen patients received active rTMS treatment; 14 patients received sham treatment. There were no differences between the active and sham groups in baseline functional connectivity. Neither treatment with rTMS nor sham therapy resulted in statistically significant functional connectivity changes in the examined brain networks.

Conclusions

The analysis did not identify any changes in neural connectivity following treatment in patients with bothersome tinnitus. These results are consistent with our findings of lack of symptom changes previously reported in the same group of patients. Measures of neural connectivity may inform future work using rTMS to better understand the possible benefits of neural stimulation for tinnitus.

Level of Evidence

1b. Laryngoscope, 126:1201–1206, 2016
Nonradial positive solutions of the ‐Laplace Emden–Fowler equation with sign‐changing weight
Authors: Kajikiya Ryuji
Published: September 2015

In this paper we study the p‐Laplace Emden–Fowler equation with a radial and sign‐changing weight in the unit ball under the Dirichlet boundary condition. We show that if the weight function is negative in the unit ball except for a small neighborhood of the boundary and positive at somewhere in this neighborhood, then no least energy solution is radially symmetric. Therefore the equation has both a positive radial solution and a positive nonradial solution. Moreover, we prove in the one dimensional case that if the neighborhood is large, then a positive solution is unique.
Elective free flap revision in the head and neck cancer patient: Indications and outcomes
Authors: Garg Ravi K. , Poore Samuel O. , Wieland Aaron M. , Mcculloch Timothy M. , Hartig Gregory K.
Published: September 2015

Elective free flap revision among head and neck cancer patients remains poorly characterized. This study evaluates patients who underwent flap revision and their surgical outcomes. Patients who underwent tumor extirpation with free flap reconstruction were identified over a 5‐year period. Elective flap revision was defined as debulking or redraping of the original free flap for functional or cosmetic reasons. Patient demographics, surgical indications, and outcomes were reviewed. One hundred and eighty‐six patients were identified, and 19 (10.2%) underwent flap revision. Revision of oral cavity flaps (n = 9, 47.4%) was performed to address excessive flap bulk compromising lip competence, speech, swallowing, mastication, or placement of a dental prosthesis. Revision of flaps resurfacing the face or neck (n = 10, 52.6%) was performed to address facial ptosis after facial nerve sacrifice, facial asymmetry, or soft tissue redundancy. Revisions were performed at an average of 7.3 months postoperatively and there was no age or gender bias toward undergoing flap revision. Patients whose flap skin paddles were used to resurface the facial or neck skin were significantly more likely to undergo elective revision than patients with an external paddle designed for flap monitoring (p < 0.01). We identified a 10% elective revision rate for head and neck free flaps in cancer patients, approximately half of which were performed to improve oral cavity function and half of which were performed to address facial ptosis or asymmetry. While there was no age or gender preference for flap revision, extensive facial or neck resurfacing was significantly associated with eventual flap revision. © 2015 Wiley Periodicals, Inc. Microsurgery 35:591–595, 2015.