bluuebunny/crossref_metadata_2025 huggingface dataset:
Cooperative communications for LTE‐advanced—relay and CoMP
Authors: Nam Young‐Han , Liu Lingjia , Zhang Jianzhong (Charlie)
Published: August 2012

The Long Term Evolution‐Advanced (LTE‐A) system is currently under development to allow for significantly higher spectral efficiency and data throughput than the LTE systems. In a wireless system based on orthogonal frequency division multiplexing with frequency reuse factor one, the achievable cell spectral efficiency is often limited by the inter‐cell interference or coverage shortage of base stations. In LTE‐A, coordinated multi‐point transmission/reception (a.k.a. multi‐cell MIMO or base station cooperation) and relaying technologies are being introduced to clear these major performance hurdles. In this paper, cooperative communication technologies being discussed in LTE‐A systems are presented, together with considerations on system design. Copyright © 2012 John Wiley & Sons, Ltd.
An Air‐Stable Fe3S4 Complex with Properties Similar to Those of the HOXair State of the Diiron Hydrogenases
Authors: Huang Yong , Gao Weiming , Åkermark Torbjörn , Li Mingrun , Åkermark Björn
Published: August 2012

A Fe3S4 complex bridged by azapropanedithiolate (adt), complex 6, was prepared as a potential model of the HOXair state of [FeFe]‐hydrogenases. Complex 6 was characterized by IR and 1H NMR spectroscopy, and its structure was determined by X‐ray crystallography. The electrochemical studies show that complex 6 is redox‐active under acidic conditions, which provides insight into the catalytic mechanism. Hydrogen evolution, driven by visible light, was observed in CH3CN/D2O solution by online mass spectroscopy.
Structural Characterization of Amidinatobismuth(III) Diazides
Authors: Lyhs Benjamin , Bläser Dieter , Wölper Christoph , Haack Rebekka , Jansen Georg , Schulz Stephan
Published: August 2012

Amidinatobismuth(III) diazides LBi(N3)2 {L1 = [tBuC(NiPr)2] (2), L2 = [tBuC(NDipp)2] (3, Dipp = 2,6‐iPr2‐C6H3)} were synthesized in high yields by metathesis reactions of the corresponding halide‐substituted complexes L1BiI2 (1) and L2BiCl2 with AgN3. Compounds 1–3 were characterized by using elemental analyses, multinuclear NMR (1H, 13C), and IR spectroscopy as well as by using single‐crystal X‐ray diffraction (for 2, 3).
Pseudo dynamic test of a deficient reinforced concrete frame upgraded with internal steel frames
Authors: Ozcelik Ramazan , Binici Baris , Kurc Ozgur
Published: August 2012

Two‐story, three‐bay reinforced concrete (RC) frames with and without internal steel frame (ISF) retrofits were tested using continuous pseudo dynamic test method. The ISFs were installed to the middle bay of the RC frame. Test results indicated that ISF retrofit was beneficial in resisting deformation demands without significant damage under simulated ground motions. The ISF shifted the failure mode of the system from a brittle to a ductile mode. The test results were compared with the results of the nonlinear time history analysis. The analysis results were capable of tracing the overall behavior of global response parameters; however, estimations of local demand parameters were less accurate. Copyright © 2012 John Wiley & Sons, Ltd.
Cationic nitrile‐functionalized Ag(I)‐ and Hg(II)‐N‐heterocyclic carbene complexes of CCC, CNC, and NCN pincer‐type carbene ligands: Synthesis, crystal structures, and characterization
Authors: Haque Rosenani A. , Zulikha H. Zetty , Ghdhayeb Mohammed Z. , Budagumpi Srinivasa , Salman Abbas Washeel
Published: August 2012

Three nitrile‐functionalized (benz)imid‐ zaolium derivatives with CCC, CNC, and NCN coordination pockets have been synthesized and isolated as the bromide salts and are converted into their hexafluorophosphate counterparts (5–7) by ligand metathesis. N‐heterocyclic carbene Ag(I)‐ and Hg(II)‐complexes (8–10 and 11–13) are readily formed in good to excellent yields from ligand precursors 5–7 and Ag2O and Hg(OAc)2, respectively. All reported compounds have been characterized by various spectral and analytical techniques, such as FTIR, 1H, and 13C NMR spectroscopy and X‐ray diffraction studies. Solid‐state structures of carbene precursors 5, 7, and an Ag(I)–carbene complex 10 have been determined crystallographically. Single crystal X‐ray crystallography of complex 10 reveals the chelation of carbene carbons to metal center in almost a linear manner. © 2012 Wiley Periodicals, Inc. Heteroatom Chem 23:486–497, 2012; View this article online at wileyonlinelibrary.com. DOI 10.1002/hc.21041
Receptor for activated C kinase 1 promotes hepatocellular carcinoma growth by enhancing mitogen-activated protein kinase kinase 7 activity
Authors: Guo Yuanyuan , Wang Wendie , Wang Jing , Feng Jiannan , Wang Qingyang , Jin Jianfeng , Lv Ming , Li Xinying , Li Yan , Ma Yuanfang , Shen Beifen , Zhang Jiyan
Published: August 2012

c-Jun N-terminal protein kinase (JNK) is a member of the mitogen-activated protein kinase (MAPK) superfamily. The activation of JNK is mediated by sequential protein phosphorylation through a MAPK module, namely, MAPK kinase kinase (MAP3K or MEKK) → MAPK kinase (MAP2K or MKK) → MAPK. Elevated levels of JNK activity have been frequently observed in hepatocellular carcinoma (HCC) and have been demonstrated to contribute to HCC growth by promoting HCC cell proliferation and resistance to tumor necrosis factor–related apoptosis-inducing ligand (TRAIL)- or Fas-mediated apoptosis. Chronic inflammation contributes to the up-regulation of JNK activity in HCC. However, it remains unknown whether aberrant JNK activity also results from some cell intrinsic defect(s). Here, we show that receptor for activated C kinase 1 (RACK1), an adaptor protein implicated in the regulation of multiple signaling pathways, could engage in a direct interaction with MKK7, the JNK-specific MAP2K, in human HCC cells. Levels of RACK1 protein show correlation with the activity of the JNK pathway in human HCC tissues and cell lines. RACK1 loss-of-function or gain-of-function analyses indicate that RACK1 enhances MKK7/JNK activity in human HCC cells. Further exploration reveals that the interaction of RACK1 with MKK7 is required for the enhancement of MKK7/JNK activity by RACK1. RACK1/MKK7 interaction facilitates the association of MKK7 with MAP3Ks, thereby enhancing MKK7 activity and promoting in vitro HCC cell proliferation and resistance to TRAIL- or Fas-mediated apoptosis as well as in vivo tumor growth. Conclusion: Overexpressed RACK1 augments JNK activity and thereby promotes HCC growth through directly binding to MKK7 and enhancing MKK7 activity. (Hepatology 2013)
Differentiated umbilical cord matrix stem cells as a new in vitro model to study early events during hepatitis B virus infection
Authors: Paganelli Massimiliano , Dallmeier Kai , Nyabi Omar , Scheers Isabelle , Kabamba Benoît , Neyts Johan , Goubau Patrick , Najimi Mustapha , Sokal Etienne M.
Published: August 2012

The role of cell differentiation state on hepatitis B virus (HBV) replication has been well demonstrated, whereas how it determines cell susceptibility to HBV entry is far less understood. We previously showed that umbilical cord matrix stem cells (UCMSC) can be differentiated towards hepatocyte-like cells in vitro. In this study we infected undifferentiated (UD-) and differentiated (D-) UCMSCs with HBV and studied the infection kinetics, comparing them to primary human hepatocytes (PHHs). UD-UCMSCs, although permissive to viral binding, had a very limited uptake capacity, whereas D-UCMSCs showed binding and uptake capabilities similar to PHHs. Likewise, asialoglycoprotein receptor (ASGPR) was up-regulated in UCMSCs upon differentiation. In D-UCMSCs, a dose-dependent inhibition of HBV binding and uptake was observed when ASGPR was saturated with known specific ligands. Subsequent viral replication was shown in D-UCMSCs but not in UD-UCMSCs. Susceptibility of UCMSCs to viral replication correlated with the degree of differentiation. Replication efficiency was low compared to PHHs, but was confirmed by (1) a dose-dependent inhibition by specific antiviral treatment using tenofovir; (2) the increase of viral RNAs along time; (3) de novo synthesis of viral proteins; and (4) secretion of infectious viral progeny. Conclusion: UCMSCs become supportive of the entire HBV life cycle upon in vitro hepatic differentiation. Despite low replication efficiency, D-UCMSCs proved to be fully capable of HBV uptake. Overall, UCMSCs are a unique human, easily available, nontransformed, in vitro model of HBV infection that could prove useful to study early infection events and the role of the cell differentiation state on such events. (Hepatology 2013)
MicroRNA-140 acts as a liver tumor suppressor by controlling NF-κB activity by directly targeting DNA methyltransferase 1 (Dnmt1) expression
Authors: Takata Akemi , Otsuka Motoyuki , Yoshikawa Takeshi , Kishikawa Takahiro , Hikiba Yohko , Obi Shuntaro , Goto Tadashi , Kang Young Jun , Maeda Shin , Yoshida Haruhiko , Omata Masao , Asahara Hiroshi , Koike Kazuhiko
Published: August 2012

MicroRNAs (miRNAs) are small RNAs that regulate the expression of specific target genes. While deregulated miRNA expression levels have been detected in many tumors, whether miRNA functional impairment is also involved in carcinogenesis remains unknown. We investigated whether deregulation of miRNA machinery components and subsequent functional impairment of miRNAs are involved in hepatocarcinogenesis. Among miRNA-containing ribonucleoprotein complex components, reduced expression of DDX20 was frequently observed in human hepatocellular carcinomas, in which enhanced nuclear factor-κB (NF-κB) activity is believed to be closely linked to carcinogenesis. Because DDX20 normally suppresses NF-κB activity by preferentially regulating the function of the NF-κB-suppressing miRNA-140, we hypothesized that impairment of miRNA-140 function may be involved in hepatocarcinogenesis. DNA methyltransferase 1 (Dnmt1) was identified as a direct target of miRNA-140, and increased Dnmt1 expression in DDX20-deficient cells hypermethylated the promoters of metallothionein genes, resulting in decreased metallothionein expression leading to enhanced NF-κB activity. MiRNA-140-knockout mice were prone to hepatocarcinogenesis and had a phenotype similar to that of DDX20 deficiency, suggesting that miRNA-140 plays a central role in DDX20 deficiency-related pathogenesis. Conclusion: These results indicate that miRNA-140 acts as a liver tumor suppressor, and that impairment of miRNA-140 function due to a deficiency of DDX20, a miRNA machinery component, could lead to hepatocarcinogenesis. (Hepatology 2013)
Monitoring Bile Acid Transport in Single Living Cells Using a Genetically Encoded FöRster Resonance Energy Transfer Sensor
Authors: van der Velden Lieke M. , Golynskiy Misha V. , Bijsmans Ingrid T. G. W. , van Mil Saskia W. C. , Klomp Leo W. J. , Merkx Maarten , van de Graaf Stan F.J.
Published: August 2012

Bile acids are pivotal for the absorption of dietary lipids and vitamins and function as important signaling molecules in metabolism. Here, we describe a genetically encoded fluorescent bile acid sensor (BAS) that allows for spatiotemporal monitoring of bile acid transport in single living cells. Changes in concentration of multiple physiological and pathophysiological bile acid species were detected as robust changes in Förster resonance energy transfer (FRET) in a range of cell types. Specific subcellular targeting of the sensor demonstrated rapid influx of bile acids into the cytoplasm and nucleus, but no FRET changes were observed in the peroxisomes. Furthermore, expression of the liver fatty acid binding protein reduced the availability of bile acids in the nucleus. The sensor allows for single cell visualization of uptake and accumulation of conjugated bile acids, mediated by the Na+-taurocholate cotransporting protein (NTCP). In addition, cyprinol sulphate uptake, mediated by the putative zebrafish homologue of the apical sodium bile acid transporter, was visualized using a sensor based on the zebrafish farnesoid X receptor. The reversible nature of the sensor also enabled measurements of bile acid efflux in living cells, and expression of the organic solute transporter αβ (OSTαβ) resulted in influx and efflux of conjugated chenodeoxycholic acid. Finally, combined visualization of bile acid uptake and fluorescent labeling of several NTCP variants indicated that the sensor can also be used to study the functional effect of patient mutations in genes affecting bile acid homeostasis.

Conclusion:

A genetically encoded fluorescent BAS was developed that allows intracellular imaging of bile acid homeostasis in single living cells in real time.
Further Withaphysalin Derivatives from Acnistus arborescens
Authors: Maia Ana Isabel V. , Braz‐Filho Raimundo , Silveira Edilberto R. , de Simone Carlos Alberto , Pessoa Otília Deusdênia L.
Published: August 2012

Two new epimeric chlorinated withaphysalins, rel‐(4β,5β,6α,18S,22R)‐ and rel‐(4β,5β,6α,18R,22R)‐6‐chloro‐18,20‐epoxy‐18‐ethoxy‐4,5‐dihydroxy‐1‐oxowitha‐2,24‐diene‐26,22‐lactone (1 and 2 resp.), together with the new rel‐(4β,5β,6α,18R,22R)‐6‐chloro‐18,20‐epoxy‐4,5‐dihydroxy‐18‐methoxy‐1‐oxowitha‐2,24‐diene‐26,22‐lactone (3) and rel‐(3β,4β,5β,6β,18R,22R)‐5,6:18,20‐diepoxy‐3,18‐diethoxy‐4‐hydroxy‐1‐oxowith‐24‐ene‐26,22‐lactone (4) were isolated from the leaves of Acnistus arborescens and named withaphysalins T–W, respectively. The final structures and the complete 1H‐ and 13C‐NMR assignments of the three chlorowithaphysalins 1–3 were performed by means of HR‐ESI‐MS and 1D‐ and 2D‐NMR experiments, including COSY, HSQC, and HMBC, beside comparison with spectral data of analogous compounds from the literature. The structure of 4 was also confirmed by means of a single‐crystal X‐ray diffraction analysis.
Diketopiperazine Alkaloids Produced by the Endophytic Fungus Aspergillus fumigatus from the Stem of Erythrophloeum fordiiOliv.
Authors: Liu Yu‐Xi , Ma Shuang‐Gang , Wang Xiao‐Jing , Zhao Nan , Qu Jing , Yu Shi‐Shan , Dai Jun‐Gui , Wang Ying‐Hong , Si Yi‐Kang
Published: August 2012

Four new diketopiperazine alkaloids, rel‐(8R)‐9‐hydroxy‐8‐methoxy‐18‐epi‐fumitremorgin C (1), rel‐(8S)‐19,20‐dihydro‐9,20‐dihydroxy‐8‐methoxy‐9,18‐di‐epi‐fumitremorgin C (2), rel‐(8S,19S)‐19,20‐dihydro‐9,19,20‐trihydroxy‐8‐methoxy‐9‐epi‐fumitremorgin C (3), and (3S,8S,9S,18S)‐8,9‐dihydroxyspirotryprostatin A (4), together with the eight known compounds 5–12, were isolated from the endophytic fungus Aspergillus fumigatus. The structures of the new compounds were determined by extensive spectroscopic methods including HR‐ESI‐MS, NMR, and CD experiments. Compound 12 showed weak inhibitory activity in vitro against the release of β‐glucuronidase in rat polymorphonuclear leukocytes induced by the platelet‐activating factor. None of the twelve compounds exhibited detectable cytotoxic activities toward five human tumor cell lines (HCT‐8, Bel‐7402, BGC‐823, A549, and A2780) in the MTT assay.
The Reactions of α‐Ylidene (Vinylidene, Benzylidene, Styrylmethylidene) Bis[carbonyls] with Copper Mono/Bis[carbonylcarbenoids]
Authors: Merey Gökçe , Kaya Mustafa , Anaç Olcay
Published: August 2012

The [Cu(acac)2]‐catalyzed reactions of various α,β,γ,δ‐unsaturated bis‐ketones/bis‐esters/bis‐keto esters with dimethyl diazomalonate and ethyl diazoacetate were studied. Total steric/electronic convenience of the present reaction paths was investigated. Methoxy/nitro substituents in m‐/p‐positions on benzylidene biscarbonyls did not alter the general routes of the reactions, supporting concerted mechanism. Dihydrobenzoxepine/oxepine formation was sterically sensitive to the related pre‐ring conformation, and dihydrofurans were effected by both charge control and steric factors.
Alkaloids from the Stems of Glycosmis pentaphylla
Authors: Yang Guang‐Zhong , Wu Yi , Chen Yu
Published: August 2012

A new simple carbazole alkaloid, 4‐(7‐hydroxy‐3‐methoxy‐6‐methyl‐9H‐carbazol‐4‐yl)but‐3‐en‐2‐one (1), and two new dimeric carbazole alkaloids, bisglybomine B (2) and biscarbalexine A (3), together with seven known alkaloids, were isolated from the stems of Glycosmis pentaphylla. Their structures were elucidated by spectroscopic methods, especially 2D‐NMR techniques.
A New Megastigmane Palmitate and a New Oleanane Triterpenoid from Aster yomenaMakino
Authors: Jin Qinglong , Jin Hong‐Guang , Kim A Ryun , Woo Eun‐Rhan
Published: August 2012

A new megastigmane palmitate, 9‐oxomegastigm‐5(13)‐ene‐2β‐palmitate (1), and a new oleanane triterpenoid, (3β)‐3,23,28‐trihydroxyolean‐12‐en‐11‐one (2), together with three known oleanane‐type triterpenoids, β‐amyrin (3), erythrodiol (4), and (3β)‐olean‐12‐ene‐3,23,28‐triol (5), were isolated from the aerial parts of Aster yomena (Asteraceae). Their structures were identified based on 1D‐ and 2D‐NMR analysis, including 1H,1H‐COSY, HSQC, HMBC, and NOESY techniques.
Improved Synthesis of Indirubin Derivatives by Sequential Build‐Up of the Indoxyl Unit: First Preparation of Fluorescent Indirubins
Authors: Riepl Herbert M. , Urmann Corinna
Published: August 2012

Indirubin, present in extracts of Isatis tinctoria and some other plant species, has promising cytotoxicity against a variety of cell lines by inhibition of cyclin‐dependent kinases. Chemical synthesis of its derivatives relies on the combination of isatins and 2,3‐dihydro‐1H‐indol‐3‐one (‘indoxyl’) derivatives and usually yields indigo as well as other by‐products. Inspection of the hydrolysis of the long‐known condensation products of 2‐thioxothiazolidin‐4‐one with isatins gave useful hints for an improved synthesis of indirubins: this reaction does not yield quinoline derivatives but 2‐(2,3‐dihydro‐2‐oxo‐1H‐indol‐3‐ylidene)‐2‐sulfanyl acetic acids. By substitution of the sulfanyl group in this oxindoles with anilines and straightforward cyclization under Nazarov conditions, a broad variety of indirubins substituted in the indoxyl ring system are thus available, usually in very good purity and yield. Use of naphthylamines in this reaction sequence yields various fluorescent substances with λfl at ca. 630 nm.
Modified Riemschneider Reaction of 3‐Thiocyanatoquinolinediones
Authors: Rudolf Ondřej , Mrkvička Vladimír , Lyčka Antonín , Rouchal Michal , Klásek Antonín
Published: August 2012

The Riemschneider reaction of 3‐thiocyanatoquinoline‐2,4(1H,3H)‐diones with conc. H2SO4 was investigated. Using different reaction conditions, 13 types of reaction products were isolated. Compounds bearing a Me, Et, or Bu group at C(3) afforded mainly [1,3]thiazolo[5,4‐c]quinoline‐2,4‐diones and 1,9b‐dihydro‐9b‐hydroxythiazolo[5,4‐c]quinoline‐2,4‐diones. In the case of the 3‐Bu derivatives of the starting compounds, C‐debutylation was also observed. If a Bn group is present at C(3), rapid C‐debenzylation of the starting thiocyanates occurred, yielding [1,3]oxathiolo[4,5‐c]quinoline‐2,4‐diones, and mixtures of mono‐, di‐, and trisulfides derived from 4‐hydroxy‐3‐sulfanylquinoline‐2‐ones. The reaction mechanism of all of the transformations is discussed. All new compounds were characterized by IR, 1H‐ and 13C‐NMR, and EI and ESI mass spectra, and in some cases, 15N‐NMR spectra were also used to characterize new compounds.
Synthesis of Aib‐Pro Oligopeptides by Repeated Azirine Coupling with the Aib‐Pro Synthon
Authors: Stoykova Svetlana A. , Linden Anthony , Heimgartner Heinz
Published: August 2012

A new synthesis of (Aib‐Pro)n oligopeptides (n=2, 3, and 4) via azirine coupling by using the dipeptide synthon methyl N‐(2,2‐dimethyl‐2H‐azirin‐3‐yl)‐L‐prolinate (1b; Fig. 1) is presented. The most important feature of the employed protocol is that no activation of the acid component is necessary, i.e., no additional reagents are required, and the coupling reaction is performed under mild conditions at room temperature. As an attempt to provide an answer to the question of the preferred conformation of the prepared molecules, we carried out experiments by using NMR techniques and X‐ray crystallography. For example, in the case of the hexapeptide 11, it was possible to compare the conformations in the crystalline state and in solution. After the selective hydrolysis of the methyl ester p‐BrBz‐(Aib‐Pro)4‐OMe (13) under basic conditions, the corresponding octapeptide acid was obtained, which was then converted into the octapeptide amide p‐BrBz‐(Aib‐Pro)4‐NHC6H13 (15) by using standard coupling conditions and activating reagents (HOBt/TBTU/DIEA) of the peptide synthesis. The conformation of this compound, as well as those of the tetrapeptides 14 and 18, was also established by X‐ray crystallography and in solution by NMR techniques. In the crystalline state, a β‐bend ribbon structure is the preferred conformation, and similar conformations are formed in solution.
Preparation and Characterization of NewC2‐ andC1‐Symmetric Nitrogen, Oxygen, Phosphorous, and Sulfur Derivatives and Analogs of TADDOL. Part III
Authors: Seebach Dieter , Beck Albert K. , Bichsel Hans‐Ulrich , Pichota Arkadius , Sparr Christof , Wünsch Ralf , Schweizer W. Bernd
Published: August 2012

A brief overview is presented of the field of organocatalysis using chiral H‐bond donors, chiralBrønstedacids, and chiral counter‐anions (Fig. 1). The role of TADDOLs (=α,α,α′,α′‐tetraaryl‐1,3‐dioxolane‐4,5‐dimethanols) as H‐bond donors and the importance of an intramolecular H‐bond for acidity enhancement are discussed. Crystal structures of TADDOLs and of their N‐, S‐, and P‐analogs (Figs. 2and3) point the way to proposals of mechanistic models for the action of TADDOLs as organocatalysts (Scheme 1). Simple experimental two‐step procedures for the preparation of the hitherto strongest known TADDOL‐derived acids, the bicyclic phosphoric acids (2inScheme 2) and of a phosphoric‐trifluorosulfonic imide (9inScheme 4), are disclosed. The mechanism of sulfinamide formation in reactions of TADDAMIN with trifluoro‐sulfonylating reagents is discussed (Scheme 3). pKaMeasurements of TADDOLs and analogs in DMSO (reported in the literature;Fig. 5) and in MeO(CH2)2OH/H2O (described herein;Fig. 6) provide information about further possible applications of this type of compounds as strong chiralBrønstedacids in organocatalysis.
Experimental study of free convection heat transfer and condensation of vapor of humid air over an inclined cold tube
Authors: Nabovati Behnam , Yaghoubi Mahmood , Avara Abdollah
Published: August 2012

In this study condensation heat transfer on a cold inclined circular cylinder due to natural convection for various conditions is investigated experimentally. The cylinder is placed in an isolated test room to permit pure natural circulation of ambient air. Ambient temperature and humidity of the test room are controlled by a refrigeration cycle and humidifying. The ambient relative air humidity changed in the range of 30 to 50% and temperature from 25 to 35 °C. The ethylene‐glycol/water solution is used as a refrigerant to control and keep the temperature of the test section at a constant value. The cold surface temperature is varied from 2 to 6 °C. The condensation rate and heat flux are found to depend mainly on time, temperature difference between ambient air and cold surface, ambient relative humidity, and tube inclination. Results are plotted for various conditions with respect to time. The experimental results are used to propose a correlation to predict the condensate mass flow rate for free convection heat transfer. © 2012 Wiley Periodicals, Inc. Heat Trans Asian Res; Published online in Wiley Online Library (wileyonlinelibrary.com/journal/htj). DOI 10.1002/htj.21015
Endogenous inhibitor proteins that connect Ser/Thr kinases and phosphatases in cell signaling
Authors: Eto Masumi , Brautigan David L.
Published: August 2012

Protein phosphatase activity acts as a primary determinant of the extent and duration of phosphorylation of cellular proteins in response to physiological stimuli. Ser/Thr protein phosphatase‐1 (PP1) belongs to the PPP superfamily, and is associated with regulatory subunits that confer substrate specificity, allosteric regulation, and subcellular compartmentalization. In addition, all eukaryotic cells contain multiple heat‐stable proteins that originally were thought to inhibit phosphatase catalytic subunits released from the regulatory subunits, as a fail‐safe mechanism. However, discovery of C‐kinase‐activated PP1 inhibitor, Mr of 17 kDa (CPI‐17) required fresh thinking about the endogenous inhibitors as specific regulators of particular phosphatase complexes, acting in addition to, not instead of, regulatory subunits. The cellular actions of the endogenous inhibitors are controlled by phosphorylation, connecting them to kinase pathways. More recent progress has unveiled additional functions of PP1 inhibitor‐2 (I‐2), including regulation of protein kinases. Transcriptional mechanisms govern the expression levels of CPI‐17 in response to stimuli. If true for other inhibitor proteins, they have the potential of being diagnostic markers for pathological conditions. We discuss specific examples of PP1 inhibitor proteins regulating particular cellular functions and the rationale for incorporating phosphatase inhibitor proteins in development of new therapeutic strategies. © 2012 IUBMB IUBMB Life, 2012
Temporal summation of second pain: Variability in responses to a fixed protocol
Authors: Anderson R.J. , Craggs J.G. , Bialosky J.E. , Bishop M.D. , George S.Z. , Staud R. , Robinson M.E.
Published: August 2012

Background

Temporal summation of second pain (TSSP) is relevant for the study of central sensitization, and refers to increased pain evoked by repetitive stimuli at a constant intensity. While the literature reports on participants whose pain ratings increase with successive stimuli, response to a TSSP protocol can be variable. The aim of this study was to characterize the full range of responses to a TSSP protocol in pain‐free adults.

Method

Three hundred twelve adults received a train of brief, repetitive heat stimuli at a fixed temperature and rated the intensity of second pain after each pulse. TSSP response (Δ in pain ratings) was quantified using the most common methods in the literature, and response groups were formed: TSSP (Δ > 0), no change (Δ = 0), and temporal decrease in second pain (TDSP) (Δ < 0). A cluster analysis was performed on the Δ values to empirically derive response groups.

Results

Depending on how TSSP response was quantified, 61–72% of the sample demonstrated TSSP, 11–28% had no change in pain ratings and 0–20% demonstrated TDSP. The cluster analysis found that the majority (59%) of participants fell in the no change cluster, 29% clustered into the TSSP group and 12% in the TDSP cluster.

Conclusions

Using a fixed thermal paradigm, pain‐free adults exhibit substantial variability in response to a TSSP protocol not well characterized by group‐mean slopes. Studies are needed to determine TSSP response patterns in clinical samples, identify predictors of response and determine the clinical implications of response variability.
Coffee attenuates fibrosis by decreasing the expression of TGF‐β and CTGF in a murine model of liver damage
Authors: Arauz Jonathan , Moreno Marina Galicia‐ , Cortés‐Reynosa Pedro , Salazar Eduardo Pérez , Muriel Pablo
Published: August 2012

This study was performed to evaluate the antifibrotic properties of coffee in a model of liver damage induced by repeated administration of thioacetamide (TAA) in male Wistar rats. In this study, cirrhosis was induced by chronic TAA administration and the effects of co‐administration of conventional caffeinated coffee or decaffeinated coffee (CC, DC, respectively) for 8 weeks were evaluated. TAA administration elevated serum alkaline phosphatase (AP), γ‐glutamyl transpeptidase (γ‐GTP) and alanine aminotransferase (ALAT), liver lipid peroxidation, collagen content, depleted liver glycogen and glutathione peroxidase (GPx) activity. Additionally increased levels of a number of proteins were detected including transforming growth factor‐beta (TGF‐β), connective tissue growth factor (CTGF) and alpha‐smooth muscle actin (α‐SMA), and matrix metalloproteinase (MMP)‐2, 9 and 13. Coffee suppressed most of the changes produced by TAA. Histopathological analysis was in agreement with biochemical and molecular findings. These results indicate that coffee attenuates experimental cirrhosis; the action mechanisms are probably associated with its antioxidant properties and mainly by its ability to block the elevation of the profibrogenic cytokine TGF‐β and its downstream effector CTGF. Various components of coffee that have been related to such a favorable effect include caffeine, coffee oils kahweol, cafestol and antioxidant substances; however, no definite evidence for the role of these components has been established. These results support earlier findings suggesting a beneficial effect of coffee on the liver. However, more basic clinical studies must be performed to confirm this hypothesis. Copyright © 2012 John Wiley & Sons, Ltd.
Emerging molecular networks in Burkitt's lymphoma
Authors: Mangani Davide , Roberti Annalisa , Rizzolio Flavio , Giordano Antonio
Published: August 2012

Burkitt's lymphoma (BL), one of the most aggressive tumors affecting humans, characterized by the constitutive activation of the Myc oncogene together with the alteration of many other genetic and epigenetic factors. Among them, the INK4a/ARF locus has been well documented to play a central role in BL. Recently, we have discovered that simultaneous deregulation of both DNA methylation patterns and the ubiquitin‐dependent proteolysis system is required to completely inactive the INK4/ARF locus, opening new possibilities for treating Burkitt's lymphoma. In this review, we integrate our discovery with the general view of BL and propose a new comprehensive approach to analyze and manage this aggressive disease. J. Cell. Biochem. 114: 35–38, 2012. © 2012 Wiley Periodicals, Inc.
Perspective from the heart: The potential of human pluripotent stem cell‐derived cardiomyocytes
Authors: Xu Xiu Qin , Sun William
Published: August 2012

Human pluripotent stem cells (hPSC) are self‐renewing cells with the potential to differentiate into a variety of human cells. They hold great promise for regenerative medicine and serve as useful in vitro models for studying human biology. For the past few years, there is vast interest in applying these cells to advance cardiovascular medicine. Human cardiomyocytes can be readily generated from hPSC and they have been characterized extensively with regards to molecular and functional properties. They have been transplanted into animal models of cardiovascular diseases and also shown to be potentially useful reagents for drug discovery. Yet, despite great progress in this field, significant technical hurdles remain before these cells could be used clinically or for pharmaceutical research and development. Further research using novel approaches will be required to overcome these bottlenecks. J. Cell. Biochem. 114: 39–46, 2012. © 2012 Wiley Periodicals, Inc.
Modeling host–pathogen interactions: H. sapiens as a host and C. difficile as a pathogen
Authors: Tomar Namrata , De Rajat K.
Published: August 2012

Many complex mechanisms in immunological studies cannot be measured by experiments, but can be analyzed by mathematical simulations. Using theoretical modeling techniques, general principles of host–pathogen system interactions can be explored and clinical treatment schedules can be optimized to lower the microbial toxin burden and side effects in the host system. In this study, we use a computational modeling technique that aims to explain the host–pathogen interactions and suggests how the host system tries to survive from the pathogen attack. The method generates data on reaction fluxes in a pathway at steady state. A set of constraints is incorporated and an objective function for the minimization of toxin expression, with respect to some parameters such as concentration of signaling molecules, is formulated. We have integrated the toxin expression regulatory pathway in Clostridium difficile, apoptosis and mitogen‐activated protein kinase pathways in an infected host (Homo sapiens). We have found that due to the minimization of the toxin expression, the signal flow values for most of the survival genes are at the higher side, whereas it is the reverse for most of the proapoptotic genes. We have observed increased signal flow values of the molecules for extracellular regulated kinase as compared with the molecules present in c‐Jun NH2‐terminal kinase/p38 pathways. In light of these observations, we can hypothesize that lower toxin level in a pathogen implies higher chance of host survival. Copyright © 2012 John Wiley & Sons, Ltd.
Contrast‐enhanced multidetector‐row computed tomography vs. time‐resolved magnetic resonance angiography vs. contrast‐enhanced perfusion MRI: Assessment of treatment response by patients with inoperable chronic thromboembolic pulmonary hypertension
Authors: Ohno Yoshiharu , Koyama Hisanobu , Yoshikawa Takeshi , Nishio Mizuho , Matsumoto Sumiaki , Matsumoto Keiko , Aoyama Nobukazu , Nogami Munenobu , Murase Kenya , Sugimura Kazuro
Published: August 2012

Purpose:

To compare therapeutic effect assessment capability of multidetector‐row computed tomography (MDCT), magnetic resonance angiography (MRA), and dynamic perfusion MRI for chronic thromboembolic pulmonary hypertension (CTEPH) patients.

Materials and Methods:

Twenty‐four consecutive CTEPH patients treated with conventional therapy underwent pre‐ and posttherapeutic MDCT, MRA, dynamic perfusion MRI, 6‐minute walk distance (6‐MWD), cardiac ultrasound (US), and right heart catheterization. According to therapeutic results, all patients were divided into response (n = 13) and nonresponse (n = 11) groups. CTEPH indexes for MDCT (CTEPHCT) and MRA (CTEPHMRA) were calculated on the basis of embolic burden. Pulmonary perfusion parameter maps were generated from all perfusion MR data, followed by determination of improvements in mean perfusion parameter at regions of interest (ROIs) for each patient. Receiver operating characteristic (ROC)‐based positive tests were performed to determine the feasible threshold values for distinguishing two groups. Finally, diagnostic capabilities were compared by means of McNemar's test.

Results:

When feasible threshold values adapted, specificity (90.9 〈10/11〉%, P < 0.05) and accuracy (95.8 〈23/24〉%, P < 0.05) for improvement in pulmonary blood flow were significantly higher than those for CTEPHCTA (specificity: 36.4 〈4/11〉%, accuracy: 70.8 〈17/24〉%).

Conclusion:

Dynamic perfusion MRI has better capability for assessment of therapeutic effect on CTEPH patients than does MDCT. J. Magn. Reson. Imaging 2012;36:612–623. © 2012 Wiley Periodicals, Inc.
MRI temporal acceleration techniques
Authors: Tsao Jeffrey , Kozerke Sebastian
Published: August 2012

In recent years, there has been an explosive growth of magnetic resonance imaging (MRI) techniques that allow faster scan speed by exploiting temporal or spatiotemporal redundancy of the images. These techniques improve the performance of dynamic imaging significantly across multiple clinical applications, including cardiac functional examinations, perfusion imaging, blood flow assessment, contrast‐enhanced angiography, functional MRI, and interventional imaging, among others. The scan acceleration permits higher spatial resolution, increased temporal resolution, shorter scan duration, or a combination of these benefits. Along with the exciting developments is a dizzying proliferation of acronyms and variations of the techniques. The present review attempts to summarize this rapidly growing topic and presents conceptual frameworks to understand these techniques in terms of their underlying mechanics and connections. Techniques from view sharing, keyhole, k‐t, to compressed sensing are covered. J. Magn. Reson. Imaging 2012;36:543–560. © 2012 Wiley Periodicals, Inc.
9,10‐Diphenylanthracene as a matrix for MALDI‐MS electron transfer secondary reactions
Authors: Nazim Boutaghou M. , Cole Richard B.
Published: August 2012

The most common secondary‐ionization mechanism in positive ion matrix‐assisted laser desorption/ionization (MALDI) involves a proton transfer reaction to ionize the analyte. Peptides and proteins are molecules that have basic (and acidic) sites that make them susceptible to proton transfer. However, non‐polar, aprotic compounds that lack basic sites are more difficult to protonate, and creating charged forms of this type of analyte can pose a problem when conventional MALDI matrices are employed. In this case, forming a radical molecular ion through electron transfer is a viable alternative, and certain matrices may facilitate the process. In this work, we investigate the performance of a newly developed electron‐transfer secondary reaction matrix: 9,10‐diphenylanthracene (9,10‐DPA). The use of 9,10‐DPA as matrix for MALDI analysis has been tested using several model compounds. It appears to promote ionization through electron transfer in a highly efficient manner as compared to other potential matrices. Thermodynamic aspects of the observed electron transfers in secondary‐ionization reactions were also considered, as was the possibility for kinetically controlled/endothermic, electron‐transfer reactions in the MALDI plume. Copyright © 2012 John Wiley & Sons, Ltd.
Desorption electrospray ionization ‐ orbitrap mass spectrometry of synthetic polymers and copolymers
Authors: Friia Manel , Legros Véronique , Tortajada Jeanine , Buchmann William
Published: August 2012

Desorption ElectroSpray Ionization (DESI) ‐ Orbitrap Mass Spectrometry (MS) was evaluated as a new tool for the characterization of various industrial synthetic polymers (poly(ethylene glycol), poly(propylene glycol), poly(methylmethacrylate), poly(dimethylsiloxane)) and copolymers, with masses ranging from 500 g.mol−1 up to more than 20 000 g.mol−1. Satisfying results in terms of signal stability and sensitivity were obtained from hydrophobic surfaces (HTC Prosolia) with a mixture water/methanol (10/90) as spray solvent in the presence of sodium salt. Taking into account the formation of multiplied charged species by DESI‐MS, a strategy based on the use of a deconvolution software followed by the automatic assignment of the ions was described allowing the rapid determination of Mn, Mw and PDI values. DESI‐Orbitrap MS results were compared to those obtained from matrix‐assisted laser desorption/ionization‐ time‐of‐flight MS and gel permeation chromatography. An application of DESI‐Orbitrap MS for the detection and identification of polymers directly from cosmetics was described. Copyright © 2012 John Wiley & Sons, Ltd.
GC‐MS of amaryllidaceous galanthamine‐type alkaloids
Authors: Berkov Strahil , Viladomat Francesc , Codina Carles , Suárez Sergio , Ravelo Angel , Bastida Jaume
Published: August 2012

Galanthamine‐type alkaloids produced by plants of the Amaryllidaceae family are potent acetylcholinesterase inhibitors. One of them, galanthamine, has been marketed as a hydrobromide salt for the treatment of Alzheimer's disease. In the present work, gas chromatography with electron impact mass spectrometry (GC‐EIMS) fragmentation of 12 reference compounds isolated from various amaryllidaceous plants and identified by spectroscopic methods (1D and 2D nuclear magnetic resonance, circular dichroism, high‐resolution MS (HRMS) and EIMS) was studied by tandem mass spectrometry (GC‐MS/MS) and accurate mass measurements (GC‐HRMS). The studied compounds showed good peak shape and efficient GC separation with a GC‐MS fragmentation pattern similar to that obtained by direct insertion probe. With the exception of galanthamine‐N‐oxide and N‐formylnorgalanthamine, the galanthamine‐type compounds showed abundant [M]+. and [M‐H]+ ions. A typical fragmentation pattern was also observed, depending on the substituents of the skeleton. Based on the fragmentation pathways of reference compounds, three other galanthamine‐type alkaloids, including 3‐O‐(2′‐butenoyl)sanguinine, which possesses a previously unelucidated structure, were identified in Leucojum aestivum ssp. pulchelum, a species endemic to the Balearic islands. GC‐MS can be successfully applied to Amaryllidaceae plant samples in the routine screening for potentially new or known bioactive molecules, chemotaxonomy, biodiversity and identification of impurities in pharmaceutical substances. Copyright © 2012 John Wiley & Sons, Ltd.
Non‐vacuum field desorption ion source implemented under super‐atmospheric pressure
Authors: Chen Lee Chuin , Rahman Md. Matiur , Hiraoka Kenzo
Published: August 2012

Standard field desorption (FD) ionization is implemented under high vacuum condition. In this paper, non‐vacuum FD is performed under a super‐atmospheric pressure environment using untreated tungsten wires as FD emitter, and the ion source was coupled to a commercial linear ion trap mass spectrometer. The operating pressure of the ion source was 6 bars which was high enough to provide sufficient dielectric strength to the working gas so that the high voltage that was required for FD could be applied to the emitter without occurrence of electrical discharge. Non‐volatile sample deposited on the bare tungsten wire FD emitter was heated by flowing direct current through the emitter. Similar to vacuum FD, the formation of conical protrusion of the liquefied sample layer under the strong electric field was also observed. Using the present ion source, high pressure field‐desorption of polar neutral compounds, organic salts and ionic liquids is demonstrated. Copyright © 2012 John Wiley & Sons, Ltd.
1912: a titanic year for mass spectrometry
Authors: Downard Kevin M.
Published: August 2012

The 1912 sinking of the Titanic continues to capture the imagination and fascination of the general public. The year coincides with the birth of mass spectrometry that began with the cathode ray experiments performed by Joseph John (J. J.) Thomson in Cambridge. Modifications made to Thomson's cathode ray apparatus by Francis William Aston, resulted in an increase in the brightness of the positive rays that aided their detection. This led to the discovery of heavy isotopes for many of the chemical elements in the ensuing decades. As the discovery of 22Ne was reported in 1913, another of Thomson's students was taking part in an expedition to help save future ocean liners from the fate of the Titanic. Geoffrey Ingram Taylor took part in the first ice patrol of the North Atlantic in 1913 aboard the SS Scotia to investigate the formation and position of icebergs. This article, 100 years on, describes Taylor's work and its impact on safe ocean passage across the Atlantic. Copyright © 2012 John Wiley & Sons, Ltd.
Impact of hepatectomy for huge solitary hepatocellular carcinoma
Authors: Ariizumi Shun‐ichi , Kotera Yoshihito , Takahashi Yutaka , Katagiri Satoshi , Yamamoto Masakazu
Published: August 2012

Background

To evaluate the surgical outcome of patients with huge solitary hepatocellular carcinoma (HCC, ≥10 cm in diameter) without major vascular invasion.

Methods

We retrospectively studied 177 patients with huge HCC (≥10 cm in diameter) who underwent hepatectomy from 1990 to 2008. Surgical outcomes and clinicopathological characteristics were compared among 54 patients with solitary HCC without a major portal vein tumor thrombus (MPVT), 53 patients with multiple HCCs without MPVT, and 70 patients who have HCC with MPVT.

Results

The mean tumor size and indocyanine green retention rate at 15 min showed no significant difference among patients groups. The overall 5‐year survival rate was significantly higher in patients with solitary HCC (79%) than in patients with multiple HCCs (31%, P < 0.0001) and MPVT (17%, P < 0.0001). In patients who underwent curative surgery, the 5‐year disease‐free survival rate was significantly higher in patients with solitary HCC (48%) than in patients with multiple HCCs (12%, P = 0.0008) and MPVT (12%, P = 0.0003). Multivariate analysis showed solitary HCC to be a significant independent prognostic factor for overall survival and disease‐free survival.

Conclusions

Patients with solitary HCC without MPVT show a favorable surgical outcome even for tumor size ≥10 cm in diameter. J. Surg. Oncol. 2013;107:408–413. © 2012 Wiley Periodicals, Inc.
Diagnostic and prognostic significance of serum MicroRNAs in colorectal cancer
Authors: Menéndez Pablo , Villarejo Pedro , Padilla David , Menéndez José M. , Montes Jose A. Rodríguez
Published: August 2012

MicroRNAs are short non‐coding RNA molecules involved in the regulation of gene expression. There are few studies related to the determination of serum microRNAs in colorectal cancer. The identification of microRNAs in peripheral blood as noninvasive markers of tumor disease may lead to potential applications, although further clinical studies focusing on serum microRNAs are required to determine their clinical significance for the diagnosis and prognosis outcome of colorectal cancer. J. Surg. Oncol. 2013;107:217–220. © 2012 Wiley Periodicals, Inc.
THAP1 mutations and dystonia phenotypes: Genotype phenotype correlations
Authors: Xiromerisiou Georgia , Houlden Henry , Scarmeas Nikolaos , Stamelou Maria , Kara Eleanna , Hardy John , Lees Andrew J. , Korlipara Prasad , Limousin Patricia , Paudel Reema , Hadjigeorgiou Georgios M. , Bhatia Kailash P.
Published: August 2012

THAP1 mutations have been shown to be the cause of DYT6. A number of different mutation types and locations in the THAP1 gene have been associated with a range of severity and dystonia phenotypes, but, as yet, it has been difficult to identify clear genotype phenotype patterns. Here, we screened the THAP1 gene in a further series of dystonia cases and evaluated the mutation pathogenicity in this series as well as previously reported mutations to investigate possible phenotype‐genotype correlations. THAP1 mutations have been identified throughout the coding region of the gene, with the greatest concentration of variants localized to the THAP1 domain. In the additional cases analyzed here, a further two mutations were found. No obvious, indisputable genotype‐phenotype correlation emerged from these data. However, we managed to find a correlation between the pathogenicity of mutations, distribution, and age of onset of dystonia. THAP1 mutations are an important cause of dystonia, but, as yet, no clear genotype‐phenotype correlations have been identified. Greater mutation numbers in different populations will be important and mutation‐specific functional studies will be essential to identify the pathogenicity of the various THAP1 mutations. © 2012 Movement Disorder Society
Shock wave treatment improves nerve regeneration in the rat
Authors: Mense Siegfried , Hoheisel Ulrich
Published: August 2012

Introduction: The aims of the experiments were to: (1) determine whether low‐energy shock wave treatment accelerates the recovery of muscle sensitivity and functionality after a nerve lesion; and (2) assess the effect of shock waves on the regeneration of injured nerve fibers. Methods: After compression of a muscle nerve in rats the effects of shock wave treatment on the sequelae of the lesion were tested. In non‐anesthetized animals, pressure pain thresholds and exploratory activity were determined. The influence of the treatment on the distance of nerve regeneration was studied in immunohistochemical experiments. Results: Both behavioral and immunohistochemical data show that shock wave treatment accelerates the recovery of muscle sensitivity and functionality and promotes regeneration of injured nerve fibers. Conclusion: Treatment with focused shock waves induces an improvement of nerve regeneration in a rodent model of nerve compression. Muscle Nerve 47: 702–710, 2013