bluuebunny/crossref_metadata_2025 huggingface dataset:
Resistance Properties of a Bend in Dense‐Phase Pneumatic Conveying of Pulverized Coal under High Pressure
Authors: Zhou Y. , Chen X.‐p. , Liang C. , Xu P.
Published: December 2010

Experiments of high‐pressure dense‐phase pneumatic conveying of pulverized coal with different mean particle sizes using nitrogen were carried out in an experimental test facility with a conveying pressure of up to 4 MPa. The effects of three representative operating parameters (solids‐to‐gas mass flow ratio, conveying pressure, mean particle size) on the total pressure drop were examined. The pressure drops across the horizontal and vertical bends were analyzed by experimental and analytical calculation. The results show that the pressure drop due to gas friction is of much less significance, while the pressure drop due to the solids friction component of the total pressure drop dominates. There exists a relationship between the pressure drop due to solids kinetic energy loss and mass flux of solids.
Configurational and Constitutional Information Storage: Multiple Dynamics in Systems Based on Pyridyl and Acyl Hydrazones
Authors: Chaur Manuel N. , Collado Daniel , Lehn Jean‐Marie
Published: December 2010

The CN group of hydrazones can undergo E/Z isomerization both photochemically and thermally, allowing the generation of a closed process that can be tuned by either of these two physical stimuli. On the other hand, hydrazine‐exchange reactions enable a constitutional change in a given hydrazone. The two classes of processes: 1) configurational (physically stimulated) and 2) constitutional (chemically stimulated) give access to short‐term and long‐term information storage, respectively. Such transformations are reported herein for two hydrazones (bis‐pyridyl hydrazone and 2‐pyridinecarboxaldehyde phenylhydrazone) that undergo a closed, chemically or physically driven process, and, in addition, can be locked or unlocked at will by metal‐ion coordination or removal. These features also extend to acyl hydrazones derived from 2‐pyridinecarboxaldehyde. Similarly to the terpydine‐like hydrazones, such acyl hydrazones can undergo both constitutional and configurational changes, as well as metal‐ion coordination. All these types of hydrazones represent dynamic systems capable of acting as multiple state molecular devices, in which the presence of coordination sites furthermore allows the metal ion‐controlled locking and unlocking of the interconversion of the different states.
Total Synthesis of Iso‐ and Bongkrekic Acids: Natural Antibiotics Displaying Potent Antiapoptotic Properties
Authors: Français Antoine , Leyva‐Pérez Antonio , Etxebarria‐Jardi Gorka , Peña Javier , Ley Steven V.
Published: December 2010

For over five decades, owing to their antiapoptotic activities, bongkrekic and isobongkrekic acids have generated interest from the scientific community. Here, we disclose full details of our investigation into the synthesis of isobongkrekic acid, which culminated in its first preparation and features various palladium‐catalysed cross‐couplings and Takai olefination reactions. Access to bongkrekic acid is also reported by this route. These syntheses involve the preparation and use of new general building blocks which could find wider applications.
Rapid and Quantitative Disulfide Bond Formation for a Polypeptide Chain Using a Cyclic Selenoxide Reagent in an Aqueous Medium
Authors: Arai Kenta , Dedachi Kenichi , Iwaoka Michio
Published: December 2010

To elucidate the reaction mechanism of the disulfide (SS) bond formation reaction of a polypeptide molecule with a water‐soluble selenoxide reagent, trans‐3,4‐dihydroxyselenolane oxide (DHSox), short‐term oxidation experiments were carried out for the reduced state (R) of a recombinant hirudin CX‐397 variant at pH 7.0 and 25 °C. In the reaction, R was oxidized sequentially to one‐SS, two‐SS, and three‐SS intermediate ensembles within 1 min. The kinetic analysis revealed that the three second‐order rate constants for the SS formation are proportional to the number of thiol groups existing in the reactant SS intermediates, indicating the stochastic nature of the SS formation. Ab initio calculation at the HF/6‐31++G(d,p) level in water by using the polarizable continuum model suggested that the SS formation reaction is highly exothermic and proceeds via a reactive thioselenurane intermediate with a distorted linear O‐Se‐S linkage. The results clearly demonstrated that the rate‐determining step of the SS formation reaction is the first bimolecular process between a thiol substrate and DHSox rather than the subsequent process to release a SS product.
Reducing ovarian cancer death rates through screening
Authors: Hartge Patricia
Published: December 2010

In this issue, Havrilesky and colleagues argue that the biologic diversity of ovarian cancer means that it will be even harder than expected to save lives through screening. Empirical results from the current randomized clinical trials will provide the strongest evidence about the potential for reducing ovarian cancer death through screening.
Patient navigation for American Indians undergoing cancer treatment
Authors: Guadagnolo B. Ashleigh , Boylan Amy , Sargent Michele , Koop David , Brunette Deb , Kanekar Shalini , Shortbull Vanessa , Molloy Kevin , Petereit Daniel G.
Published: December 2010

BACKGROUND:

A study was undertaken to assess patient navigation utilization and its impact on treatment interruptions and clinical trial enrollment among American Indian cancer patients.

METHODS:

Between February 2004 and September 2009, 332 American Indian cancer patients received patient navigation services throughout cancer treatment. The patient navigation program provided culturally competent navigators to assist patients with navigating cancer therapy, obtaining medications, insurance issues, communicating with medical providers, and travel and lodging logistics. Data on utilization and trial enrollment were prospectively collected. Data for a historical control group of 70 American Indian patients who did not receive patient navigation services were used to compare treatment interruptions among those undergoing patient navigation during curative radiation therapy (subgroup of 123 patients).

RESULTS:

The median number of contacts with a navigator was 12 (range, 1‐119). The median time spent with the navigator at first contact was 40 minutes (range, 10‐250 minutes), and it was 15 minutes for subsequent contacts. Patients treated with radiation therapy with curative intent who underwent patient navigation had fewer days of treatment interruption (mean, 1.7 days; 95% confidence interval [CI], 1.1‐2.2 days) than historical controls who did not receive patient navigation services (mean, 4.9 days; 95% CI, 2.9‐6.9 days). Of the 332 patients, 72 (22%; 95% CI, 17%‐26%) were enrolled on a clinical treatment trial or cancer control protocol.

CONCLUSIONS:

Patient navigation was associated with fewer treatment interruptions and relatively high rates of clinical trial enrollment among American Indian cancer patients compared with national reports. Cancer 2011. © 2010 American Cancer Society.
P2P schema‐mapping over network‐bound XML data
Authors: Comito Carmela , Talia Domenico
Published: December 2010

The rise in availability of web‐based data sources has led to new challenges in data integration systems for obtaining decentralized, wide‐scale sharing of data preserving semantics. In this paper, we present a framework for integrating heterogeneous XML data sources distributed over a large‐scale, highly dynamic network of autonomous nodes. We highlight a query reformulation algorithm to combine and query‐distributed XML databases through a decentralized point‐to‐point mediation process among the different data sources by using P2P schema‐mappings. More precisely, our integration model is based on path‐to‐path mappings, using the XPath language. We demonstrate the usefulness and scalability of our ideas and algorithms with a detailed set of experiments. Finally, we discuss our experience implementing the above‐cited query reformulation algorithm as a Web service within the GDIS system, a service‐based Grid architecture. We have evaluated GDIS on several real‐world schemas with promising results. Copyright © 2010 John Wiley & Sons, Ltd.
Photophysics of New Photostable Rylene Derivatives: Applications in Single‐Molecule Studies and Membrane Labelling
Authors: Davies Melari , Jung Christophe , Wallis Philipp , Schnitzler Tobias , Li Chen , Müllen Klaus , Bräuchle Christoph
Published: December 2010

Three new photostable rylene dyes for applications in single molecule studies and membrane labelling have been synthesized and their photophysical properties were characterized. These dyes differ in the number of polyethylene glycol (PEG) chains attached to the core structure which is either a perylene derivate or a terrylene derivate. One perylene and one terrylene dye is modified with two PEG chains, and another terrylene derivate has four PEG chains. The results show that the terrylene dye with four PEG chains (4‐PEG‐TDI) forms soluble nonfluorescing H‐aggregates in water, so that the absorption bands are blue‐shifted with respect to those of the fluorescing monomeric form. The presence of a surfactant such as Pluronic P123 leads to the disruption of the aggregates due to the formation of monomers in micelles and a strong increase in fluorescence. Application for labelling cell membranes can be considered for this dye since it adsorbs in a similar way as monomer to a lipid bilayer. Furthermore a single‐molecule study of all three rylene dyes in polymeric films of PMMA showed excellent photostability with respect to photobleaching, far above the photostability of other common water‐soluble dyes, such as Oxazine‐1, Atto647N, Cy5, Alexa647 and Rhodamin6G. Especially 4‐PEG‐TDI seems to be a promising dye for membrane labelling with its high photostability.
Enhanced Photoactivity in Bilayer Films with Buried Rutile–Anatase Heterojunctions
Authors: Romero‐Gomez Pablo , Borras Ana , Barranco Angel , Espinos Juan P. , Gonzalez‐Elipe Agustin R.
Published: December 2010

Herein, we study the photoactivity of anatase–rutile bilayer thin films consisting of an anatase overlayer of variable thickness from some tenths to some hundred nanometers deposited onto a rutile thin film. As references single anatase layers of equivalent thickness were deposited onto silicon. All the films were characterized by X‐ray diffraction (XRD), scanning electron microscopy (SEM) and Raman spectroscopy. The photoactivity of the samples was assessed by following the evolution with the UV illumination time of both the wetting angle on the thin film surface and the decoloration of a dye in a water solution. While a similar efficiency is found for the first type of experiments irrespective of the anatase thickness, in the second type a maximum in the photoactivity is found for a thickness of the anatase layer of about 130 nm. This enhanced photoactivity in bilayer systems with a buried anatase–rutile heterojunction is related to the formation of different Schottky potential barriers in the anatase layer, depending on its thickness and the substrate (i.e. rutile or SiO2) where it is deposited.
Analytic model for spread‐spectrum clock generator circuit characterization
Authors: Xia Tian
Published: December 2010

The spread‐spectrum clock generator (SSCG) is one of the most efficient techniques to reduce the radiated emission of electronic devices. Despite its popularity, there exists no analysis that can be used as the design guidance to accurately project SSCG performance. In this paper, we develop a mathematical model to analyze SSCG EMI reduction and the clock period deviation performance. For model validation, Cadence Spectre simulations are conducted. Copyright © 2010 John Wiley & Sons, Ltd.
A new efficient SC integrator scheme for high‐speed low‐power applications
Authors: Amoroso F. A. , Pugliese A. , Cappuccino G.
Published: December 2010

A new solution to implement efficient switched‐capacitor (SC) integrators is presented. In the proposed scheme, voltage buffers are opportunely introduced in order to prevent direct connection between the output and the capacitive feedback network of the circuit that characterizes classical SC integrator topologies during the charge transfer phase. Design guidelines to optimize the settling performances of the proposed circuit are also given. To demonstrate the possible advantages of the new solution, the proposed integrator is designed in a commercial 0.35−µm CMOS technology. It is shown that compared with classical SC integrator topologies, the proposed configuration allows a significant improvement of the integrator speed to be achieved for a given power budget. Copyright © 2010 John Wiley & Sons, Ltd.
World's oldest donor‐recipient solid organ transplantation?
Authors: Mistry Bhargav , McKeever Brian , Phadke Gautam , Mahale Adit
Published: December 2010

The incidence of chronic kidney disease is rising rapidly among the elderly. Improved results have been noted among the elderly when a living donor is available. We report on the world's oldest donor‐recipient solid organ transplantation, with a combined age of 167 years and 337 days.
Screening of proteinuria in young adults: Is it worthwhile?
Authors: El‐Tayeb M. , El Setouhy M. , El Sayed H. , Elshahawy Y. , Sany D. , Bichari W. , Shaban A.
Published: December 2010

BACKGROUND

The prevalence of chronic kidney disease is increasing rapidly worldwide, and recent data indicate that overt disease is the tip of the iceberg of covert disease. Data on the prevalence and incidence of proteinuria in young adults are scarce. This lack of knowledge is an obstacle to the establishment of prevention programs for chronic kidney disease, especially in developing countries.

SETTING AND PARTICIPANTS

Urine screening for proteinuria was carried out in a cohort of young adults in a student hostel of Ain Shams University, Cairo, Egypt. Fresh morning urine samples were collected and tested for proteinuria by dipstick analysis. Participants with persistent proteinuria were referred to the university hospital for further evaluation for the presence of kidney disease.

RESULTS

Of 1,260 apparent healthy students screened, 67.7% were males and 32.3% were females. Their mean age was 20.2 ± 1.2 years. 3.3% were hypertensive, and proteinuria was detected in 47 (3.7%) in the ﬁrst screening test. At the second screening test, persistent proteinuria was found in 10 students (0.8% of the original cohort). Of these, 4 (0.3%) had proteinuria more than 0.5 g/24 h, but all of them refused renal biopsy.

CONCLUSIONS

Urine dipstick is an inexpensive way to screen for proteinuria in developing countries, but it must be done twice to exclude transient and intermittent proteinuria. Routine screening for proteinuria in this particular young adult population is not recommended due to its low diagnostic yield.
Identification of CJC‐1295, a growth‐hormone‐releasing peptide, in an unknown pharmaceutical preparation
Authors: Henninge John , Pepaj Milaim , Hullstein Ingunn , Hemmersbach Peter
Published: December 2010

Several peptide drugs are being manufactured illicitly, and in some cases they are being made available to the public before entering or completing clinical trials. At the request of Norwegian police and customs authorities, unknown pharmaceutical preparations suspected to contain peptide drugs are regularly subjected to analysis. In 2009, an unknown pharmaceutical preparation was submitted for analysis by liquid chromatography‐high resolution tandem mass spectrometry (LC‐HRMS/MS). The preparation was found to contain a 29 amino acid peptide with a C‐terminal amide function. Based on the interpretation of mass spectrometric data, an amino acid sequence was proposed. The sequence is consistent with a peptide currently marketed under the name CJC‐1295. CJC‐1295 is a releasing factor for growth hormone and is therefore considered a Prohibited Substance under Section S2 of the WADA Prohibited List. This substance has potential performance‐enhancing effects, it is readily available, and there is reason to believe that it is being used within the bodybuilding community. Copyright © 2010 John Wiley & Sons, Ltd.
Cp*–‐Ruthenium–Nickel‐Based H2‐Evolving Electrocatalysts as Bio‐inspired Models of NiFe Hydrogenases
Authors: Canaguier Sigolène , Fontecave Marc , Artero Vincent
Published: December 2010

Three dinuclear nickel–ruthenium complexes [Ni(xbsms)RuCp*(L)](PF6) [H2xbsms = 1,2‐bis(4‐mercapto‐3,3‐dimethyl‐2‐thiabutyl)benzene; Cp* = pentamethylcyclopentadienyl; L = CH3CN, CO and O2] are reported that act as bio‐inspired mimics of NiFe hydrogenases. Because of an increased electron density at the metal centres in comparison with the previously described [Ni(xbsms)RuCp(L)](PF6) (Cp = cyclopentadienyl) analogues, these compounds catalyze the evolution of hydrogen from Et3NH+ in DMF with an overpotential reduced by around 50 mV, thereby corroborating a previously established structure–function relationship [Eur. J. Inorg. Chem. 2007, 18, 2613–2626; Chem. Eur. J. 2009, 15, 9350–9364]. In addition, the steric protection provided by the bulky Cp*– ligand results in an increased catalytic rate and stability upon cycling.
Oxepinamides: Novel Liver X Receptor Agonists from Aspergillus puniceus
Authors: Lu Xin‐Hua , Shi Qing‐Wen , Zheng Zhi‐Hui , Ke Ai‐Bing , Zhang Hua , Huo Chang‐Hong , Ma Ying , Ren Xiao , Li Ye‐Ying , Lin Jie , Jiang Qin , Gu Yu‐Cheng , Kiyota Hiromasa
Published: December 2010

Four novel oxepin‐containing pyrimidines, namely oxepinamides D–G (1–4), were isolated from cultures of Aspergillus puniceus F02Z‐1744. The structures of 1–4 were elucidated by analyzing their spectroscopic data generated by 1D and 2D NMR and MS methods. The configurations of 1 and 2 were established based on single‐crystal X‐ray crystallographic analysis. All four compounds 1–4 showed transcriptional activation on Liver X Receptor α (LXRα) with EC50 values of 10.6, 12.8, 13.6, and 12.1 μM, respectively.
Construction of the 5,10b‐Phenanthridine Skeleton Using [3+2]‐Cycloaddition of a Non‐Stabilized Azomethine Ylide: Total Synthesis of (±)‐Maritidine and (±)‐Crinine Alkaloids
Authors: Pandey Ganesh , Gupta Nishant R. , Gadre Smita R.
Published: December 2010

Vicinal quaternary and tertiary stereocenters of the 5,10b‐phenanthridine skeleton 1 are constructed simultaneously in one step by the [3+2]‐cycloaddition of non‐stabilized azomethine ylide 9, generated by sequential double desilylation of 10 utilizing silver(I) fluoride as a one‐electron oxidant. The regio‐ as well as stereochemical origin of this cycloaddition reaction is explained through a favorable transition state 9″. The strategy is successfully applied for the total synthesis of the biologically active alkaloids (±)‐maritidine (1a), (±)‐crinine (1b), and their analogues (1d, 1e, and 1f).
Acid‐Catalyzed [3,3] Sigmatropic Rearrangement of N‐Cbz‐Diaryl Hydrazide for the Synthesis of Mono‐N‐Cbz‐1,1′‐biaryl‐2,2′‐diamine
Authors: Suh Sung‐Eun , Park In‐Keol , Lim Byeong‐Yun , Cho Cheon‐Gyu
Published: December 2010

N‐Cbz‐Diaryl hydrazides undergo acid‐catalyzed [3,3] sigmatropic rearrangement to afford N‐Cbz‐1,1′‐biaryl‐2,2′‐diamines. The resultant products can be versatile synthetic platforms for a wide variety of C2‐ and/or nonsymmetric axially chiral ligands and organocatalysts.
Chemical Synthesis and Biological Evaluation of Second‐Generation Palmerolide A Analogues
Authors: Ravu Vengala Rao , Leung Gulice Y. C. , Lim Chek Shik , Ng Sin Yee , Sum Rong Ji , Chen David Y.‐K.
Published: December 2010

In this communication, second‐generation analogues of palmerolide A, a recently reported cytotoxic agent against melanoma cancer cells, were rationally designed, synthesized, and biologically evaluated. Structural variations of the enamide side chain and the C1–C8 segment of palmerolide A revealed a narrow structure–activity relationship window of the newly synthesized compounds. In addition, mechanistic and pharmacological studies were performed to assess the therapeutic potential of palmerolide A.
Hsp72 is an early and sensitive biomarker to detect acute kidney injury
Authors: Barrera‐Chimal Jonatan , Pérez‐Villalva Rosalba , Cortés‐González Cesar , Ojeda‐Cervantes Marcos , Gamba Gerardo , Morales‐Buenrostro Luis E. , Bobadilla Norma A.
Published: December 2010

This study was designed to assess whether heat shock protein Hsp72 is an early and sensitive biomarker of acute kidney injury (AKI) as well as to monitor a renoprotective strategy. Seventy‐two Wistar rats were divided into six groups: sham‐operated and rats subjected to 10, 20, 30, 45 and 60 min of bilateral ischemia (I) and 24 h of reperfusion (R). Different times of reperfusion (3, 6, 9, 12, 18, 24, 48, 72, 96 and 120 h) were also evaluated in 30 other rats subjected to 30 min of ischemia. Hsp72 messenger RNA (mRNA) and protein levels were determined in both kidney and urine. Hsp72‐specificity as a biomarker to assess the success of a renoprotective intervention was evaluated in rats treated with different doses of spironolactone before I/R. Renal Hsp72 mRNA and protein, as well as urinary Hsp72 levels, gradually increased relative to the extent of renal injury induced by different periods of ischemia quantified by histomorphometry as a benchmark of kidney damage. Urinary Hsp72 increased significantly after 3 h and continued rising until 18 h, followed by restoration after 120 h of reperfusion in accord with histopathological findings. Spironolactone renoprotection was associated with normalization of urinary Hsp72 levels. Accordingly, urinary Hsp72 was significantly increased in patients with clinical AKI before serum creatinine elevation. Our results show that urinary Hsp72 is a useful biomarker for early detection and stratification of AKI. In addition, urinary Hsp72 levels are sensitive enough to monitor therapeutic interventions and the degree of tubular recovery following an I/R insult.
Absorptivity and its dependence on heat source temperature and degree of thermal breakdown
Authors: Försth Michael , Roos Arne
Published: December 2010

The spectral absorptivity of 62 products has been measured in the wavelength region of 0.3–20 µm. Effective absorptivity for fire‐induced heat radiation typically lies in the range of 0.75–0.95. It was found that the effective absorptivity varies significantly with the temperature of the heat source. This has implications on the heating of a surface. The effect is more important when the absorptivity is used as input for calculations of ignition temperature and thermal inertia. It was also found that the absorptivity of radiation from fires for products exposed to irradiation in many cases decreased with increased exposure time. This is surprising since, for example, wood that is darkened when exposed to heat obviously has a higher absorptivity in the visual part of the spectrum than fresh non‐darkened wood. The reason that was identified for this is because the absorptivity in the IR drops, and measurement results are given which clearly illustrate this. Copyright © 2010 John Wiley & Sons, Ltd.
A FE‐based algorithm for the inverse natural convection problem
Authors: Wong J. C.‐F. , Yuan P.
Published: December 2010

Several numerical algorithms for solving inverse natural convection problems are revisited and studied. Our aim is to identify the unknown strength of a time‐varying heat source via a set of coupled nonlinear partial differential equations obtained by the so‐called finite element consistent splitting scheme (CSS) in order to get a good approximation of the unknown heat source from both the measured data and model results, by minimizing a functional that measures discrepancies between model and measured data. Viewed as an optimization problem, the solutions are obtained by means of the conjugate gradient method. A second‐order CSS in time involving the direct problem, the adjoint problem, the sensitivity problem and a system of sensitivity functions is used in order to enhance the numerical accuracy obtained for the unknown heat source function. A spatial discretization of all field equations is implemented using equal‐order and mixed finite element methods. Numerical experiments validate the proposed optimization algorithms that are in good agreement with the existing results. Copyright © 2010 John Wiley & Sons, Ltd.
Deep shelf trilobite biofacies from the upper Katian (Upper Ordovician) of the Grangegeeth Terrane, eastern Ireland
Authors: Owen Alan W. , Romano Michael
Published: December 2010

The trilobite fauna of the upper Katian (mid‐Ashgill in terms of Anglo‐Welsh chronostratigraphy) Oriel Brook Formation in the Grangegeeth Terrane, eastern Ireland comprises 16 species. It is dominated numerically by mesopelagic cyclopygids (Cyclopyge cf. marginata Hawle and Corda and much rarer Symphysops sp.), which comprise 63% of the 156 identifiable sclerites known unequivocally from the formation. Other elements of the trilobite fauna include species of Staurocephalus, Phillipsinella, Nankinolithus and the agnostids Trinodus and Sphaeragnostus. The abundance of cyclopygids in a terrane interpreted as lying within the Iapetus Ocean closer to Laurentia than the Anglo‐Welsh sector of Avalonia is consistent with the Late Katian spread of cyclopygids onto low latitude shelves seen in Quebec and Maine in eastern North America, Girvan in SE Scotland and Co. Clare in the Irish Central Terrane. With the exception of the agnostid trilobites, whose mode of life is strongly debated, associated benthic trilobites lacking eyes are fairly rare and the bottom‐dwelling fauna does not conform to the atheloptic assemblages that typified many mid‐ to high latitude Ordovician outer shelf and upper slope settings. The benthic assemblage can be considered in terms of a bathymetrically arranged spectrum of faunas and is closest to that of the deep shelf Phillipsinella parabola—Staurocephalus clavifrons fauna, known from the Upper Ordovician of Avalonia and Baltica and to some extent marginal Gondwana and South China. This is the first record of such a fauna from Laurentia or its marginal terranes and reflects the Late Ordovician breakdown of provincialism in the Iapetus Ocean. The deep‐water setting is compatible with that of the associated Foliomena brachiopod fauna. Copyright © 2010 John Wiley & Sons, Ltd.
Overexpression of Cholesterol 7α-Hydroxylase Promotes Hepatic Bile Acid Synthesis and Secretion and Maintains Cholesterol Homeostasis Δ
Authors: Li Tiangang , Matozel Michelle , Boehme Shannon , Kong Bo , Nilsson Lisa-Mari , Guo Grace , Ellis Ewa , Chiang John Y. L.
Published: December 2010

We reported previously that mice overexpressing cytochrome P450 7a1 (Cyp7a1;

Cyp7a1-tg

mice) are protected against high fat diet–induced hypercholesterolemia, obesity, and insulin resistance. Here, we investigated the underlying mechanism of bile acid signaling in maintaining cholesterol homeostasis in

Cyp7a1-tg

mice.

Cyp7a1-tg

mice had two-fold higher Cyp7a1 activity and bile acid pool than did wild-type mice. Gallbladder bile acid composition changed from predominantly cholic acid (57%) in wild-type to chenodeoxycholic acid (54%) in

Cyp7a1-tg

mice.

Cyp7a1-tg

mice had higher biliary and fecal cholesterol and bile acid secretion rates than did wild-type mice. Surprisingly, hepatic

de novo

cholesterol synthesis was markedly induced in

Cyp7a1-tg

mice but intestine fractional cholesterol absorption in

Cyp7a1-tg

mice remained the same as wild-type mice despite the presence of increased intestine bile acids. Interestingly, hepatic but not intestinal expression of several cholesterol (adenosine triphosphate–binding cassette G5/G8 [ABCG5/G8], scavenger receptor class B, member 1) and bile acid (ABCB11) transporters were significantly induced in

Cyp7a1-tg

mice. Treatment of mouse or human hepatocytes with a farnesoid X receptor (FXR) agonist GW4064 or bile acids induced hepatic Abcg5/g8 expression. A functional FXR binding site was identified in the

Abcg5

gene promoter. Study of tissue-specific

Fxr

knockout mice demonstrated that loss of the

Fxr
, gene in the liver attenuated bile acid induction of hepatic Abcg5/g8 and gallbladder cholesterol content, suggesting a role of FXR in the regulation of cholesterol transport.

Conclusion:

This study revealed a new mechanism by which increased Cyp7a1 activity expands the hydrophobic bile acid pool, stimulating hepatic cholesterol synthesis and biliary cholesterol secretion without increasing intestinal cholesterol absorption. This study demonstrated that Cyp7a1 plays a critical role in maintaining cholesterol homeostasis and underscores the importance of bile acid signaling in regulating overall cholesterol homeostasis. (Hepatology 2011)
Loss of Histone Acetyltransferase Cofactor Transformation/Transcription Domain-Associated Protein Impairs Liver Regeneration After Toxic Injury σ
Authors: Shukla Vivek , Cuenin Cyrille , Dubey Nileshkumar , Herceg Zdenko
Published: December 2010

Organ regeneration after toxin challenge or physical injury requires a prompt and balanced cell-proliferative response; a well-orchestrated cascade of gene expression is needed to regulate transcription factors and proteins involved in cell cycle progression and cell proliferation. After liver injury, cell cycle entry and progression of hepatocytes are believed to require concerted efforts of transcription factors and histone-modifying activities; however, the actual underlying mechanisms remain largely unknown. The purpose of our study was to investigate the role of the histone acetyltransferase (HAT) cofactor transformation/transcription domain-associated protein (TRRAP) and histone acetylation in the regulation of cell cycle and liver regeneration. To accomplish our purpose, we used a TRRAP conditional knockout mouse model combined with toxin-induced hepatic injury. After we treated the mice with a carbon tetrachloride toxin, conditional ablation of the TRRAP gene in those mice severely impaired liver regeneration and compromised cell cycle entry and progression of hepatocytes. Furthermore, loss of TRRAP impaired the induction of early and late cyclins in regenerating livers by compromising histone acetylation and transcription factor binding at the promoters of the cyclin genes. Our results demonstrate that TRRAP and TRRAP/HAT-mediated acetylation play an important role in liver regeneration after toxic injury and provide insight into the mechanism by which TRRAP/HATs orchestrate the expression of the cyclin genes during cell cycle entry and progression. (Hepatology 2011)
Transforming growth factor-β adaptor, β2-spectrin, modulates cyclin dependent kinase 4 to reduce development of hepatocellular cancer
Authors: Baek Hye Jung , Pishvaian Michael J. , Tang Yi , Kim Tae Hyun , Yang Shaoxian , Zouhairi Majed El , Mendelson Jon , Shetty Kirti , Kallakury Bhaskar , Berry Deborah L. , Shin Kyung Hwan , Mishra Bibhuti , Reddy Premkumar E. , Kim Sang Soo , Mishra Lopa
Published: December 2010

Transforming growth factor beta (TGF-β) is an important regulator of cell growth, and loss of TGF-β signaling is a hallmark of carcinogenesis. The Smad3/4 adaptor protein β2-spectrin (β2SP) is emerging as a potent regulator of tumorigenesis through its ability to modulate the tumor suppressor function of TGF-β. However, to date the role of the TGF-β signaling pathway at specific stages of the development of hepatocellular carcinoma (HCC), particularly in relation to the activation of other oncogenic pathways, remains poorly delineated. Here we identify a mechanism by which β2SP, a crucial Smad3 adaptor, modulates cyclin dependent kinase 4 (CDK4), cell cycle progression, and suppression of HCC. Increased expression of β2SP inhibits phosphorylation of the retinoblastoma gene product (Rb) and markedly reduces CDK4 expression to a far greater extent than other CDKs and cyclins. Furthermore, suppression of CDK4 by β2SP efficiently restores Rb hypophosphorylation and cell cycle arrest in G1. We further demonstrate that β2SP interacts with CDK4 and Smad3 in a competitive and TGF-β-dependent manner. In addition, haploinsufficiency of

cdk4

in

β2sp+/−

mice results in a dramatic decline in HCC formation compared to that observed in

β2spZ+/−

mice.

Conclusion

: β2SP deficiency leads to CDK4 activation and contributes to dysregulation of the cell cycle, cellular proliferation, oncogene overexpression, and the formation of HCCs. Our data highlight CDK4 as an attractive target for the pharmacologic inhibition of HCC and demonstrate the importance of

β2sp+/−

mice as a model of preclinical efficacy in the treatment of HCC. (Hepatology 2011;)
Yes, the choice of performance measure does matter for ranking of us mutual funds
Authors: Ornelas José Renato Haas , Silva Júnior Antônio Francisco , Fernandes José Luiz Barros
Published: December 2010

Recent literature in performance evaluation has focused on preferences and characteristics of returns' distribution that go beyond mean and variance world. However, Eling (2008) compared the Sharpe ratio with some of these performance measures, and found virtually identical rank ordering using mutual fund data. This paper compares 13 performance measures with the traditional Sharpe Ratio using a sample of US Fixed‐Income, Equity and Asset Allocation Mutual Funds. Results show that performance measures based on absolute reward‐risk ratios have similar rankings, when the numerator (mean excess return) is the same. However, when we move to other types of performances measures, results may be significantly different. This is the case of the Manipulation‐Proof Performance Measure (MPPM), Upside Potential Ratio, and Appraisal Ratio. Results are especially different for the MPPM. Robustness checks show that some of the performance measures are very sensitive to parameters' changes. Therefore, the choice of the performance measure is actually important for mutual fund ranking and selection. As a consequence, we argue that the use of several performance measures and rankings have a positive impact on the mutual fund's industry, reducing concentration. Copyright © 2011 John Wiley & Sons, Ltd.
Discharge‐based economic valuation of irrigation water: Evidence from the Teesta River, Bangladesh
Authors: Mullick Md. Reaz Akter , Babel Mukand S , Perret Sylvain R
Published: December 2010

Studies estimating the value of irrigation water as a function of river discharge are rarely found in the literature; however, discharge‐based valuation carries significance when the in‐ and off‐stream uses are evaluated for optimal water allocation. This paper develops the total and marginal benefit functions of the key off‐stream water use, irrigation, as a function of flow in the Teesta River of Bangladesh. The field water balance approach and CROPWAT modelling are used to calculate irrigation water requirements for rice and other crops respectively. The residual imputation method is employed to estimate the value of irrigation water. In the cases of insufficient flow in the river, several scenarios based on (i) conjunctive uses of groundwater, (ii) reduction in irrigated land area and (iii) yield loss due to water stress, form the basis for establishing the total and marginal benefit functions for river water use in irrigation in the study area. Estimated marginal benefits as a function of river discharge are found to be linear with zero slopes for the first two scenarios and sloping downward for the third. Results of the study will assist water planners and managers with equitable and efficient allocation and sustainable management of the river water. Copyright © 2010 John Wiley & Sons, Ltd.
Biases in approximating log production
Authors: Sun Kai , Henderson Daniel J. , Kumbhakar Subal C.
Published: December 2010

Most empirical work in economic growth assumes either a Cobb–Douglas production function expressed in logs or a log‐approximated constant elasticity of substitution specification. Estimates from each are likely biased due to logging the model and the latter can also suffer from approximation bias. We illustrate this with a successful replication of Masanjala and Papagerogiou (The Solow model with CES technology: nonlinearities and parameter heterogeneity, Journal of Applied Econometrics 2004; 19: 171–201) and then estimate both models in levels to avoid these biases. Our estimation in levels gives results in line with conventional wisdom. Copyright © 2010 John Wiley & Sons, Ltd.
Dynamic microvascular responses with a high speed TiVi imaging system
Authors: O'Doherty Jim , McNamara Paul M. , Fitzgerald Barry W. , Leahy Martin J.
Published: December 2010

TiVi technology presents a high resolution, low speed methodology for imaging microcirculation. Recently, the TiVi system was adapted to produce a high speed system capable of analysing dynamic responses from human tissues at a frame rate of 30 frames per second. We present results based on this system by investigating dynamic responses such as arterial pulsations both from a controlled flow model and in vivo tissue sites. We also quantify the effects of sympathetic vasomotion, a biological effect which is evident in many tissue sites, and show that the effects of arterial pulsations and vasomotion on the resulting TiVi time traces are easily determined. (© 2011 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Current performance gains from utilizing the GPU or the ASIC MDGRAPE‐3 within an enhanced Poisson Boltzmann approach
Authors: Narumi Tetsu , Yasuoka Kenji , Taiji Makoto , Höfinger Siegfried
Published: December 2010

Scientific applications do frequently suffer from limited compute performance. In this article, we investigate the suitability of specialized computer chips to overcome this limitation. An enhanced Poisson Boltzmann program is ported to the graphics processing unit and the application specific integrated circuit MDGRAPE‐3 and resulting execution times are compared to the conventional performance obtained on a modern central processing unit. Speed Up factors are measured and an analysis of numerical accuracy is provided. On both specialized architectures the improvement is increasing with problem size and reaches up to a Speed Up factor of 39 × for the largest problem studied. This type of alternative high performance computing can significantly improve the performance of demanding scientific applications. © 2009 Wiley Periodicals, Inc. J Comput Chem, 2009
Analysis of p53 and NF‐κB signaling in modulating the cardiomyocyte fate during hypertrophy
Authors: Chatterjee Arunachal , Mir Saiful A. , Dutta Dipanjan , Mitra Arkadeep , Pathak Kanchan , Sarkar Sagartirtha
Published: December 2010

Cardiac hypertrophy leading to eventual heart failure is the most common cause of mortality throughout the world. The triggering mechanisms for cardiac hypertrophy are not clear but both apoptosis and cell proliferation have been reported in sections of failing hearts. In this study, we utilized both angiotensin II (AngII) treatment of cardiomyocytes and aortic ligation in rats (Rattus norvegicus, Wistar strain) for induction of hypertrophy to understand the cellular factors responsible for activation of apoptotic or anti‐apoptotic pathway. Hypertrophy markers (ANF, β‐MHC), apoptotic proteins (Bax, Bad, Fas, p53, caspase‐3, PARP), and anti‐apoptotic or cell proliferation marker proteins (Bcl2, NF‐κB, Ki‐67) were induced significantly during hypertrophy, both in vitro as well as in vivo. Co‐localization of both active caspase‐3 and Ki‐67 was observed in hypertrophied myocytes. p53 and NF‐κBp65 binding to co‐activator p300 was also increased in AngII treated myocytes. Inhibition of p53 resulted in downregulation of apoptosis, NF‐κB activation, and NF‐κB–p300 binding; however, NF‐κB inhibition did not inhibit apoptosis or p53–p300 binding. Blocking of either p53 or NF‐κB by specific inhibitors resulted in decrease in cell proliferation and hypertrophy markers, suggesting that p53 initially binds to p300 and then this complex recruits NF‐κB. Thus, these results indicate the crucial role of p53 in regulating both apoptotic and cell proliferation during hypertrophy. J. Cell. Physiol. 226: 2543–2554, 2011. © 2010 Wiley‐Liss, Inc.
Amphiphilic, low molecular weight poly(ethylene imine) derivatives with enhanced stability for efficient pulmonary gene delivery
Authors: Roesler Susanne , Koch Felix P. V. , Schmehl Thomas , Weissmann Norbert , Seeger Werner , Gessler Tobias , Kissel Thomas
Published: December 2010

Background

Poly(ethylene imine) (PEI) is a widely used transfection reagent for mammalian cells, but in vivo application of PEI 25 kDa is restricted by its toxicity. Low molecular weight (LMW) PEI is less toxic, but also less efficient than its high molecular weight equivalent, and prone to aggregation.

Method

A set of polymers was synthesized by coupling poly(ethylene glycol) (PEG) that contained either C16/18‐chains (Cx‐EO) or butyl‐poly(propylene oxide)‐co‐poly(ethylene glycol) (ButPP). Critical micelle concentration (CMC) was determined for copolymers. Polyplexes were characterized by DNA binding ability, polyplex size and aggregation, hemolysis, and cytotoxicity. Transfection efficiency was tested in vitro and in vivo in mouse lungs.

Results

Copolymers formed stable complexes with DNA, and showed enhanced complex stability in isotonic solution for at least 1 h. CMC was determined for Cx‐EO‐PEI 4.7 and 8.3 at 0.0019 and 0.0037 mM, respectively; membrane activity in a haemolysis assay was demonstrated for ButPP‐PEI: both factors possibly enhance endosomal escape effect after PEGylation. IC50 values of all synthesized polymers were in the range 6–33 ng/ml. Transfection efficiency of unmodified LMW‐PEIs was equivalent or better than that of PEI 25 as a result of aggregation in vitro. Cells treated with polyplexes of amphiphilic polymers showed reduced transfection compared to PEI 25. After instillation in mouse lungs, highest transfection efficiency was demonstrated with Cx‐EO copolymer of lowest molecular weight PEI.

Conclusions

A new set of polymers with low toxicity and high stability was synthesized, which contains promising candidates for pulmonary gene transfer, as documented by in vivo experiments in mice. Copyright © 2011 John Wiley & Sons, Ltd.
The C‐terminus of the phage λ Orf recombinase is involved in DNA binding
Authors: Curtis Fiona A. , Reed Patricia , Wilson Lindsay A. , Bowers Laura Y. , Yeo Robert P. , Sanderson John M. , Walmsley Adrian R. , Sharples Gary J.
Published: December 2010

Phage λ Orf substitutes for the activities of the Escherichia coli RecFOR proteins in vivo and is therefore implicated as a recombination mediator, encouraging the assembly of bacterial RecA onto single‐stranded DNA (ssDNA) coated with SSB. Orf exists as a dimer in solution, associates with E. coli SSB and binds preferentially to ssDNA. To help identify interacting domains we analysed Orf and SSB proteins carrying mutations or truncations in the C‐terminal region. A cluster of acidic residues at the carboxy‐terminus of SSB is known to attract multiple protein partners to assist in DNA replication and repair. In this case an alternative domain must be utilized since Orf association with SSB was unaffected by an SSB113 point mutant (P176S) or removal of the last ten residues (ΔC10). Structurally the Orf C‐terminus consists of a helix with a flexible tail that protrudes from each side of the dimer and could serve as a binding site for either SSB or DNA. Eliminating the six residue flexible tail (ΔC6) or the entire helix (ΔC19) had no significant impact on the Orf–SSB interaction. However, the OrfΔC6 protein exhibited reduced DNA binding, a feature shared by single amino acid substitutions within (W141F) or adjacent (R140A) to this region. The OrfΔC19 mutant bound poorly to DNA and secondary structure analysis in solution revealed that this truncation induces protein misfolding and aggregation. The results show that the carboxy‐terminus of Orf is involved in nucleic acid recognition and also plays an unexpected role in maintaining structural integrity. Copyright © 2010 John Wiley & Sons, Ltd.
Interaction map of the Trypanosoma cruzi ribosomal P protein complex (stalk) and the elongation factor 2
Authors: Smulski Cristian R. , Longhi Silvia A. , Ayub Maximiliano Juri , Edreira Martin M. , Simonetti Leandro , Gómez Karina A. , Basile Joaquín N. , Chaloin Olivier , Hoebeke Johan , Levin Mariano J.
Published: December 2010

The large subunit of the eukaryotic ribosome possesses a long and protruding stalk formed by the ribosomal P proteins. This structure is involved in the translation step of protein synthesis through interaction with the elongation factor 2 (EF‐2). The Trypanosoma cruzi stalk complex is composed of four proteins of about 11 kDa, TcP1α, TcP1β, TcP2α, TcP2β and a fifth TcP0 of about 34 kDa. In a previous work, a yeast two‐hybrid (Y2H) protein–protein interaction map of T. cruzi ribosomal P proteins was generated. In order to gain new insight into the assembly of the stalk, a complete interaction map was generated by surface plasmon resonance (SPR) and the kinetics of each interaction was calculated. All previously detected interactions were confirmed and new interacting pairs were found, such as TcP1β–TcP2α and TcP1β–TcP2β. Moreover P2 but not P1 proteins were able to homo‐oligomerize. In addition, the region comprising amino acids 210–270 on TcP0 was identified as the region interacting with P1/P2 proteins, using Y2H and SPR. The interaction domains on TcP2β were also mapped by SPR identifying two distinct regions. The assembly order of the pentameric complex was assessed by SPR showing the existence of a hierarchy in the association of the different P proteins forming the stalk. Finally, the TcEF‐2 gene was identified, cloned, expressed and refolded. Using SPR analysis we showed that TcEF‐2 bound with similar affinity to the four P1/P2 ribosomal P proteins of T. cruzi but with reduced affinity to TcP0. Copyright © 2010 John Wiley & Sons, Ltd.
Effects of regional warming on extreme monthly low temperatures distribution in China
Authors: Zhou Guohua , Wan Shiquan , Feng Guolin , He Wenping
Published: December 2010

Using generalised Pareto distribution (GPD) function, the regional characteristic of extreme monthly low temperatures (EMLT) distribution during 1960‐2007 in China is studied, and the potential impact of climate warming on EMLT regions in China is analysed. The results show that EMLT space distribution has latitudinal difference in China. Higher‐value EMLT events are likely to happen in northeastern and southwestern China, while EMLT variability and occurrence probability of high‐value EMLT events are less in the Yangtze and Huaihe River basin and the coast of southern China. The study indicates that climate warming impacts EMLT, and EMLT distribution responds to the climate warming over most areas of China. Copyright © 2010 Royal Meteorological Society