bluuebunny/crossref_metadata_2025 huggingface dataset:
The Heavy Chain Variable Segment Gene Repertoire in Chronic Chagas′ Heart Disease
Authors: Grippo Vanina , Mahler Evelyn , Elias Fernando E. , Cauerhff Ana , Gómez Karina A. , Tentori Maria C. , Ruiz Aurora , Vigliano Carlos A. , Laguens Ruben P. , Berek Claudia , Levin Mariano J.
Published: November 2009

Patients chronically infected with Trypanosoma cruzi develop chronic Chagas′ heart disease (cChHD). Their Ab response is suspected to be involved in the cardiac pathogenesis. Reactivity of serum Abs from these patients has been extensively studied but little is known about the diversity of the in vivo IgG repertoire. We analyzed 125 variable H chain (VH) genes and compared it to repertoires from healthy individuals, and patients with autoimmune processes and other infections. VH were from plasma cells isolated from heart tissue of three cChHD patients and from a Fab combinatorial library derived from bone marrow of another cChHD patient. The role of the parasite in shaping the Ab repertoire was assessed analyzing VH genes before and after panning against T. cruzi Ag. Among recovered VH genes, a significantly increased representation of VH4 was observed. Plasma cells at the site of cardiac infiltration showed an increased VH1 usage. CDR3 lengths were similar to the ones found in the healthy repertoire and significantly shorter than in other infections. VH derived from anti-T. cruzi Fab and plasma cells showed a higher proportion of hypermutated genes, 46.9% and 43.75%, respectively, vs 30.9% of the cChHD patient repertoire, pointing to the role of parasite Ags in the shaping of the humoral response in Chagas′ disease. No histological evidence of germinal center-like structures was observed in heart tissue. In accordance, VH analysis of heart plasmocytes revealed no evidence of clonal B cell expansion, suggesting that they migrated into heart tissue from secondary lymphoid organs.
The Runx3 Transcription Factor Augments Th1 and Down-Modulates Th2 Phenotypes by Interacting with and Attenuating GATA3
Authors: Kohu Kazuyoshi , Ohmori Hidetaka , Wong Won Fen , Onda Daisuke , Wakoh Takeshi , Kon Shunsuke , Yamashita Masakatsu , Nakayama Toshinori , Kubo Masato , Satake Masanobu
Published: November 2009

Recently, it was reported that the expression of Runt-related transcription factor 3 (Runx3) is up-regulated in CD4+ helper T cells during Th1 cell differentiation, and that Runx3 functions in a positive feed-forward manner with the T-box family transcription factor, T-bet, which is a master regulator of Th1 cell differentiation. The relative expression levels of IFN-γ and IL-4 are also regulated by the Th2-associated transcription factor, GATA3. Here, we demonstrate that Runx3 was induced in Th2 as well as Th1 cells and that Runx3 interacted with GATA3 and attenuated GATA3 transcriptional activity. Ectopic expression of Runx3 in vitro in cultured cells or transgenic expression of Runx3 in mice accelerated CD4+ cells to a Th1-biased population or down-modulated Th2 responses, in part by neutralizing GATA3. Our results suggest that the balance of Runx3 and GATA3 is one factor that influences the manifestation of CD4+ cells as the Th1 or Th2 phenotypes.
Tumor Progression Locus 2 (Map3k8) Is Critical for Host Defense againstListeria monocytogenesand IL-1β Production
Authors: Mielke Lisa A. , Elkins Karen L. , Wei Lai , Starr Robyn , Tsichlis Philip N. , O'Shea John J. , Watford Wendy T.
Published: November 2009

Tumor progression locus 2 (Tpl2, also known as Map3k8 and Cot) is a serine-threonine kinase critical in innate immunity, linking toll-like receptors (TLRs) to TNF production through its activation of ERK. Tpl2−/− macrophages have abrogated TNF production but overproduce IL-12 in response to TLR ligands. Despite enhanced IL-12 production, Tpl2−/− T cells have impaired IFN-γ production. Therefore, the role of Tpl2 in a bona fide bacterial infection where all of these cytokines are important in host defense is unclear. To address this issue, we infected Tpl2−/− mice with the model pathogen Listeria monocytogenes. We found that Tpl2−/− mice infected i.v. with L. monocytogenes had increased pathogen burdens compared with wild-type mice and rapidly succumbed to infection. Enhanced susceptibility correlated with impaired signaling through TLR2 and nucleotide-binding oligomerization domain 2, two receptors previously shown to mediate Listeria recognition. Surprisingly, TNF production in response to infection was not significantly impaired, even though Tpl2 has been implicated in the regulation of TNF. We found that the role of Tpl2 has cell-type specific effects in regulating TNF and transduces signals from some, but not all, pattern recognition receptors (PRR). In contrast to the cell-type- and receptor-specific regulation of TNF, we found that Tpl2 is essential for IL-1β production from both macrophages and dendritic cells. These studies implicate Tpl2 as an important mediator for collaboration of pattern recognition receptors with danger-associated molecular patterns to induce TNF and IL-1β production and optimal host defense.
In a Murine Tuberculosis Model, the Absence of Homeostatic Chemokines Delays Granuloma Formation and Protective Immunity
Authors: Khader Shabaana A. , Rangel-Moreno Javier , Fountain Jeffrey J. , Martino Cynthia A. , Reiley William W. , Pearl John E. , Winslow Gary M. , Woodland David L. , Randall Troy D. , Cooper Andrea M.
Published: November 2009

Mycobacterium tuberculosis infection (Mtb) results in the generation of protective cellular immunity and formation of granulomatous structures in the lung. CXCL13, CCL21, and CCL19 are constitutively expressed in the secondary lymphoid organs and play a dominant role in the homing of lymphocytes and dendritic cells. Although it is known that dendritic cell transport of Mtb from the lung to the draining lymph node is dependent on CCL19/CCL21, we show in this study that CCL19/CCL21 is also important for the accumulation of Ag-specific IFN-γ-producing T cells in the lung, development of the granuloma, and control of mycobacteria. Importantly, we also show that CXCL13 is not required for generation of IFN-γ responses, but is essential for the spatial arrangement of lymphocytes within granulomas, optimal activation of phagocytes, and subsequent control of mycobacterial growth. Furthermore, we show that these chemokines are also induced in the lung during the early immune responses following pulmonary Mtb infection. These results demonstrate that homeostatic chemokines perform distinct functions that cooperate to mediate effective expression of immunity against Mtb infection.
Does drawing facilitate older children's reports of emotionally laden events?
Authors: Patterson Tess , Hayne Harlene
Published: November 2009

Although it is well‐established that drawing about an event increases the amount of verbal information that young children provide during an interview, it is unclear whether drawing continues to facilitate children's reports as they get older. In the present experiment, 90 children, ranging from 5‐ to 12‐years old, were asked to draw and tell or to just tell about emotional events they had experienced. Children of all ages reported more information when asked to draw and tell rather than to tell only. Drawing had no negative effect on the accuracy of children's accounts. Drawing also increased the number of open‐ended questions and minimal responses that interviewers used. We conclude that drawing may be a useful tool in clinical and forensic settings with children of all ages; it increases the amount of information that children report and the number of appropriate questions that interviewers ask. Copyright © 2009 John Wiley & Sons, Ltd.
Microstructure and Texture Formation During Near Conventional Forging of an Intermetallic Ti–45Al–5Nb Alloy
Authors: Stark Andreas , Bartels Arno , Clemens Helmut , Kremmer Sascha , Schimansky Frank‐Peter , Gerling Rainer
Published: November 2009

Texture formation was studied in an intermetallic Ti‐45at%Al‐5at%Nb alloy after uniaxial compression and near conventional forging. Depending on the deformation conditions the texture of the γ‐TiAl phase is formed by pure deformation components, components related to dynamic recrystallization, or transformation components. This changing corresponds with microstructural observations. The α2‐Ti3Al and the α‐Ti(Al) phase show a similar texture as it is known for Ti and Ti‐base alloys after compressive deformation at elevated temperatures. In contrast to the γ texture, no significant change of the α/α2 texture was observed in the temperature range between 800 °C and just below the α‐transus temperature (Tα = 1295 °C).
Rapid Generation of Biologically Relevant Hydrogels Containing Long‐Range Chemical Gradients
Authors: He Jiankang , Du Yanan , Villa‐Uribe José L. , Hwang Changmo , Li Dichen , Khademhosseini Ali
Published: November 2009

Many biological processes are regulated by gradients of bioactive chemicals. Thus, the generation of materials with embedded chemical gradients may be beneficial for understanding biological phenomena and generating tissue‐mimetic constructs. Here a simple and versatile method to rapidly generate materials containing centimeter‐long gradients of chemical properties in a microfluidic channel is described. The formation of a chemical gradient is initiated by a passive‐pump‐induced forward flow and further developed during an evaporation‐induced backward flow. The gradient is spatially controlled by the backward flow time and the hydrogel material containing the gradient is synthesized via photopolymerization. Gradients of a cell‐adhesion ligand, Arg‐Gly‐Asp‐Ser (RGDS), are incorporated in poly(ethylene glycol)‐diacrylate (PEG‐DA) hydrogels to test the response of endothelial cells. The cells attach and spread along the hydrogel material in a manner consistent with the RGDS‐gradient profile. A hydrogel containing a PEG‐DA concentration gradient and constant RGDS concentration is also shown. The morphology of cells cultured on such hydrogel changes from round in the lower PEG‐DA concentration regions to well‐spread in the higher PEG‐DA concentration regions. This approach is expected to be a valuable tool to investigate the cell–material interactions in a simple and high‐throughput manner and to design graded biomimetic materials for tissue engineering applications.
A Simple and Innovative Route to Prepare a Novel Carbon Nanotube/Prussian Blue Electrode and its Utilization as a Highly Sensitive H2O2 Amperometric Sensor
Authors: Nossol Edson , Zarbin Aldo J.G.
Published: November 2009

The utilization of iron‐based species (mainly metallic iron, hematite and magnetite) encapsulated into multi‐walled carbon nanotubes (CNTs) as reactants in an electrochemical synthesis is reported for the first time in this work. Prussian blue (PB) is electrosynthesized in a heterogeneous reaction between ferricyanide ions in aqueous solution and the iron‐species encapsulated into CNTs, resulting in novel CNT/PB paste electrodes. This innovative preparation route produces an intimate contact between the PB and the CNTs, which improves the stability and redox properties of PB. The PB formation and the chemical interaction between the PB and the CNTs are confirmed by Raman spectroscopy. The electrode is employed as a hydrogen peroxide amperometric sensor, resulting in a very low limit of detection (1.94 × 10−8 mol L−1) and very high sensitivity (15.3 A cm−2 M−1).
A comparison of auditory brainstem responses and behavioral estimates of hearing sensitivity in Lemur catta and Nycticebus coucang
Authors: Ramsier Marissa A. , Dominy Nathaniel J.
Published: November 2009

Primates depend on acoustic signals and cues to avoid predators, locate food, and share information. Accordingly, the structure and function of acoustic stimuli have long been emphasized in studies of primate behavioral and cognitive ecology. Yet, few studies have addressed how well primates hear such stimuli; indeed, the auditory thresholds of most primate species are unknown. This empirical void is due in part to the logistic and economic challenges attendant on traditional behavioral testing methods. Technological advances have produced a safe and cost‐effective alternative—the auditory brainstem response (ABR) method, which can be utilized in field conditions, on virtually any animal species, and without subject training. Here we used the ABR and four methods of threshold determination to construct audiograms for two strepsirrhine primates: the ring‐tailed lemur (Lemur catta) and slow loris (Nycticebus coucang). Next, to verify the general efficacy of the ABR method, we compared our results to published behaviorally‐derived audiograms. We found that the four ABR threshold detection methods produced similar results, including relatively elevated thresholds but similarly shaped audiograms compared to those derived behaviorally. The ABR and behavioral absolute thresholds were significantly correlated, and the frequencies of best sensitivity and high‐frequency limits were comparable. However, at frequencies ≤2 kHz, ABR thresholds were especially elevated, resulting in decreased agreement with behavioral thresholds and, in Lemur, the ABR 10‐dB range starting points were more than 2 octaves higher than the behavioral points. Finally, a comparison of ABR‐ and behaviorally‐derived audiograms from various animal taxa demonstrates the widespread efficacy of the ABR for estimating frequency of best sensitivity, but otherwise suggests caution; factors such as stimulus properties and threshold definition affect results. We conclude that the ABR method is a promising technique for estimating primate hearing sensitivity, but that additional data are required to explore its efficacy for estimating low‐frequency thresholds. Am. J. Primatol. 72:217–233, 2010. © 2009 Wiley‐Liss, Inc.
Detection of access to terror‐related Web sites using an Advanced Terror Detection System (ATDS)
Authors: Elovici Yuval , Shapira Bracha , Last Mark , Zaafrany Omer , Friedman Menahem , Schneider Moti , Kandel Abraham
Published: November 2009

Terrorist groups use the Web as their infrastructure for various purposes. One example is the forming of new local cells that may later become active and perform acts of terror. The Advanced Terrorist Detection System (ATDS), is aimed at tracking down online access to abnormal content, which may include terrorist‐generated sites, by analyzing the content of information accessed by the Web users. ATDS operates in two modes: the training mode and the detection mode. In the training mode, ATDS determines the typical interests of a prespecified group of users by processing the Web pages accessed by these users over time. In the detection mode, ATDS performs real‐time monitoring of the Web traffic generated by the monitored group, analyzes the content of the accessed Web pages, and issues an alarm if the accessed information is not within the typical interests of that group and similar to the terrorist interests. An experimental version of ATDS was implemented and evaluated in a local network environment. The results suggest that when optimally tuned the system can reach high detection rates of up to 100% in case of continuous access to a series of terrorist Web pages.
Assessing risk in adolescent sexual offenders: recommendations for clinical practice
Authors: Vitacco Michael J. , Caldwell Michael , Ryba Nancy L. , Malesky Alvin , Kurus Samantha J.
Published: November 2009

Accurately predicting the likelihood that an adolescent with a sex offense history will reoffend is a precarious task that carries with it the potential for extreme consequences for the adolescent offender (e.g., lifelong public registration). Recently implemented laws regarding adolescent sex offenders are dramatically upstream of current knowledge. Several of these laws were ostensibly based on the misassumption that clinicians could accurately identify adolescents at the greatest risk for sexual recidivism. However, predicting which adolescents are at greatest risk to sexually recidivate is severely constrained by limited knowledge about which predictors are most accurately linked to sexual recidivism and uncertainty over how to best make use of instruments designed to predict recidivism. This paper reviews research on risk assessment and provides a set of recommendations for conducting risk assessments with adolescent sex offenders. Copyright © 2009 John Wiley & Sons, Ltd.
Regulation of XBP‐1 signaling during transient and stable recombinant protein production in CHO cells
Authors: Ku Sebastian C. Y. , Toh Poh Choo , Lee Yih Yean , Chusainow Janet , Yap Miranda G. S. , Chao Sheng‐Hao
Published: November 2009

X‐box binding protein 1 (XBP‐1) is a key regulator of cellular unfolded protein response (UPR). The spliced isoform of XBP‐1, XBP‐1S, is a transcription activator, which is expressed only when UPR is induced. However, the impact of recombinant protein production on the regulation of XBP‐1 signaling in CHO cells is not well understood. In this report, we cloned the Chinese hamster XBP‐1 homolog to aid the investigation of the interplay between protein productivity, culture conditions, and endogenous XBP‐1 signaling in CHO cells. Interestingly, expression of XBP‐1S is detected in the non‐producing and unstressed CHO‐K1 cells. Transient expression of recombinant erythropoietin reveals a positive correlation between XBP‐1 mRNA abundance and protein production level. However, such a correlation is not observed in batch cultivation of stable producing cell lines. The increased XBP‐1 splicing is detected in late‐phase cultures, suggesting that induction of XBP‐1S may be a result of nutrient limitations or other environmental stresses rather than that of increased intracellular accumulation of recombinant proteins. Our data suggest that XBP‐1 is a key determinant for the secretory capacity of CHO cells. Understanding its dynamic regulation hence provides a rational basis for cellular engineering strategies to improve recombinant protein secretion. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2010
Wet‐milling transgenic maize seed for fraction enrichment of recombinant subunit vaccine
Authors: Moeller Lorena , Taylor‐Vokes Raye , Fox Steve , Gan Qinglei , Johnson Lawrence , Wang Kan
Published: November 2009

The production of recombinant proteins in plants continues to be of great interest for prospective large‐scale manufacturing of industrial enzymes, nutrition products, and vaccines. This work describes fractionation by wet‐milling of transgenic maize expressing the B subunit of the heat‐labile enterotoxin of Escherichia coli (LT‐B), a potent immunogen and candidate for oral vaccine and vaccine components. The LT‐B gene was directed to express in seed by an endosperm specific promoter. Two steeping treatments, traditional steeping (TS, 0.2% SO2 + 0.5% lactic acid) and water steeping (WS, water only), were evaluated to determine effects on recovery of functional LT‐B in wet‐milled fractions. The overall recovery of the LT‐B protein from WS treatment was 1.5‐fold greater than that from TS treatment. In both steeping types, LT‐B was distributed similarly among the fractions, resulting in enrichment of functional LT‐B in fine fiber, coarse fiber and pericarp fractions by concentration factors of 1.5 to 8 relative to the whole kernels on a per‐mass basis. Combined with endosperm‐specific expression and secretory pathway targeting, wet‐milling enables enrichment of high‐value recombinant proteins in low‐value fractions, such as the fine fiber, and co‐utilization of remaining fractions in alternative industrial applications. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2010
Development of multilayered cell‐hydrogel composites using an acoustic focusing technique
Authors: Mazzoccoli Jason P. , Feke Donald L. , Baskaran Harihara , Pintauro Peter N.
Published: November 2009

Multilayered composites, composed of mammalian cells arranged in a hydrogel, have been prepared using an acoustic focusing technique. Acoustic focusing is a simple, nonchemical technique that allows for the fast arrangement of cells in matrices where the control of cell geometry is beneficial. Breast cancer cells (MDA‐MB231) were dispersed in a 30 wt % solution of poly(ethylene glycol) diacrylate (PEGDA) of molecular weight 400 at a density of 5 × 106 cells/mL of PEGDA solution. An ultrasonic field was used to organize the cells before polymerization of PEGDA. Disk‐shaped hydrogel composites, typically 1 cm in diameter and 2‐mm thick were prepared based on a PEGDA solution volume of 130 μL. At an acoustic frequency of 2.32 MHz, composites having cells positioned within concentric cylindrical shells interspersed with zones of cell‐free hydrogel were produced. The cells were located in annuli approximately 80‐μm thick and about 300 μm apart. The structure and viability of the cells within these constructs were studied using a fluorescent LIVE/DEAD assay. The viability of the cells was on the order of 50%. For the conditions used in this study, cell death was primarily attributed to exposure of cells to the PEGDA solution prior to polymerization, rather than adverse effects of polymerization or the sound field itself. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2010
‘I'll sell this and I'll buy them that’: eBay and the management of possessions as stock
Authors: Denegri‐Knott Janice , Molesworth Mike
Published: November 2009

In this paper we document practices associated with selecting and selling previously owned goods through the online auction house and marketplace, eBay. More specifically, we discuss the processes through which the economic or exchange values of previously owned goods are re‐activated and the role eBay plays in facilitating such practices. Drawing from phenomenological interviews with heavy eBay users from various backgrounds living in the South of England, we discuss key emerging themes on the ways in which eBay is used for the disposal of goods. We find that eBay fuels practices of disposal that may encourage the transformation of the humble pre‐owned good into valuable stock. Besides those curative practices which have been captured in previous research into the divestment of possessions we find that work of another kind is required to move a used good back to a commodity phase in its career. We see this as turning used goods into stock. This transformation accelerates a good's biography as it enters the realm of the owned possession and then quickly returned to a sphere of exchange. In such process, goods become assets which are reinvested to fuel promiscuous consumer behaviours.

Copyright © 2009 John Wiley & Sons, Ltd.
The sacrifice of re‐use: the travels of leftovers and family relations
Authors: Cappellini Benedetta
Published: November 2009

This paper focuses on food divestment practices surrounding the consumption of food leftovers in a domestic context. It argues that divestment practices of consuming food leftovers are not the last and disconnected point of a linear consumption process; rather they influence previous and subsequent consumption practices. Drawing on research among middle class British families it shows that consuming leftovers implies a set of practices, (classifying, selecting, storing and re‐using) which transform leftovers from polluted to clean food re‐admissible to the table. Leftovers' consumption has analogies with the process of sacrifice. It is an everyday thrift practice through which consumers produce excess value to be designated for extraordinary food consumption wherein the family as a whole entity is celebrated. Consuming leftovers requires a high degree of admission to the family and thus only family members, and some of them more than others, are called to such a sacrifice. Therefore it is not only during extraordinary food consumption that familial bonds are reinforced, rather is also during the everyday practice of consuming leftovers that familial bonds are sustained and perpetuated.

Copyright © 2009 John Wiley & Sons, Ltd.
Structural Alerts, Reactive Metabolites, and Protein Covalent Binding: How Reliable Are These Attributes as Predictors of Drug Toxicity?
Authors: Kalgutkar Amit S. , Didiuk Mary T.
Published: November 2009

In an increasing number of cases, a deeper understanding of the biochemical basis for idiosyncratic adverse drug reactions (IADRs) has aided to replace a vague perception of a chemical class effect with a sharper picture of individual molecular peculiarity. Considering that IADRs are too complex to duplicate in a test tube, and their idiosyncratic nature precludes prospective clinical studies, it is currently impossible to predict which new drugs will be associated with a significant incidence of toxicity. Because it is now widely appreciated that reactive metabolites, as opposed to the parent molecules from which they are derived, are responsible for the pathogenesis of some IADRs, the propensity of drug candidates to form reactive metabolites is generally considered a liability. Procedures have been implemented to monitor reactive‐metabolite formation in discovery with the ultimate goal of eliminating or minimizing the liabilityviarational structural modification of the problematic chemical series. While such mechanistic studies have provided retrospective insight into the metabolic pathways which lead to reactive metabolite formation with toxic compounds, their ability to accurately predict the IADR potential of new drug candidates has been challenged. There are several instances of drugs that form reactive metabolites, but only a fraction thereof cause toxicity. This review article will outline current approaches to evaluate bioactivation potential of new compounds with particular emphasis on the advantages and limitation of these assays. Plausible reason(s) for the excellent safety record of certain drugs susceptible to bioactivation will also be explored and should provide valuable guidance in the use of reactive‐metabolite assessments when nominating drug candidates for development.
Lipid‐Bilayer Permeation of Drug‐Like Compounds
Authors: Krämer Stefanie D. , Lombardi Dario , Primorac Adriana , Thomae Anita V. , Wunderli‐Allenspach Heidi
Published: November 2009

Lipid‐bilayer permeation is determinant for the disposition of xenobiotics in the body. It controls the pharmacokinetic behavior of drugs and is, in many cases, a prerequisite for intracellular targeting. Permeation ofin vivobarriers is in general predicted from lipophilicity and related parameters. This article goes beyond the empirical correlations, and elucidates the processes and their interplay determining bilayer permeation. A flip‐flop model for bilayer permeation, which considers the partitioning rate constants beside the translocation rate constants, is compared with the diffusion model based onFick's first law. According to the flip‐flop model, the ratios of aqueous volumes to barrier area can determine whether partitioning or translocation is rate‐limiting. The flip‐flop model allows permeation of anions and cations, and expands our understanding of pH‐dependent permeation kinetics. Some experimental evidences for ion‐controlled permeation at pH 7 are also included in this work.
New Ideas about the Solubility of Drugs
Authors: Box Karl , Comer John E. , Gravestock Tom , Stuart Martin
Published: November 2009

Methods are described for detecting precipitation of ionisable drugs under conditions of changing pH, estimating kinetic solubility from the onset of precipitation, and measuring solubility by chasing equilibrium. Definitions are presented for kinetic, equilibrium, and intrinsic solubility of ionisable drugs, supersaturation and subsaturation, and for chasers and non‐chasers, which are two classes of ionisable drug with significantly different solubility properties. The use of Bjerrum Curves and Neutral‐Species Concentration Profiles to depict solubility properties are described and illustrated with case studies showing super‐dissolving behaviour, conversion between crystalline forms and enhancement of solubility through supersaturation, and the use of additives and simulated gastrointestinal fluids.
Copper Transfer from Cu–Aβ to Human Serum Albumin Inhibits Aggregation, Radical Production and Reduces Aβ Toxicity
Authors: Perrone Lorena , Mothes Emmanuelle , Vignes Maeva , Mockel Anaïs , Figueroa Cindy , Miquel Marie‐Christine , Maddelein Marie‐Lise , Faller Peter
Published: November 2009

Amyloid‐β peptides (Aβ) and the protein human serum albumin (HSA) interact in vivo. They are both localised in the blood plasma and in the cerebrospinal fluid. Among other functions, HSA is involved in the transport of the essential metal copper. Complexes between Aβ and copper ions have been proposed to be an aberrant interaction implicated in the development of Alzheimer's disease, where Cu is involved in Aβ aggregation and production of reactive oxygen species (ROS). In the present work, we studied copper‐exchange reaction between Aβ and HSA or the tetrapeptide DAHK (N‐terminal Cu‐binding domain of HSA) and the consequence of this exchange on Aβ‐induced ROS production and cell toxicity. The following results were obtained: 1) HSA and DAHK removed CuII from Aβ rapidly and stoichiometrically, 2) HSA and DAHK were able to decrease Cu‐induced aggregation of Aβ, 3) HSA and DAHK suppressed the catalytic HO. production in vitro and ROS production in neuroblastoma cells generated by Cu–Aβ and ascorbate, 4) HSA and DAHK were able to rescue these cells from the toxicity of Cu–Aβ with ascorbate, 5) DAHK was more potent in ROS suppression and restoration of neuroblastoma cell viability than HSA, in correlation with an easier reduction of CuII–HSA than Cu–DAHK by ascorbate, in vitro. Our data suggest that HSA is able to decrease aberrant CuII–Aβ interaction. The repercussion of the competition between HSA and Aβ to bind Cu in the blood and brain and its relation to Alzheimer's disease are discussed.
Shape‐ and Size‐Specific Chemistry of Ag Nanostructures in Catalytic Ethylene Epoxidation
Authors: Christopher Phillip , Linic Suljo
Published: November 2009

Catalytic selectivity in the epoxidation of ethylene to form ethylene oxide on alumina‐supported silver catalysts is dependent on the geometric structure of catalytically active Ag particles and reaction conditions. Shape and size controlled synthesis of Ag nanoparticles is used to show that silver nanocubes exhibit higher selectivity than nanowires and nanospheres. For a given shape, larger particles offer improved selectivity. The enhanced selectivity toward ethylene oxide is attributed to the nature of the exposed Ag surface facets; Ag nanocubes and nanowires are dominated by (100) surface facet and Ag nanospheres are dominated by (111). Furthermore, the concentration of undercoordinated surface sites is related to diminished selectivity to ethylene oxide. We demonstrate that a simple model can account for the impact of chemical and physical factors on the reaction selectivity. These observations have also been used to design a selective catalyst for the ethylene epoxidation reaction.
New Strategies to Phosphino–Phosphonium Cations and Zwitterions
Authors: Geier Stephen J. , Dureen Meghan A. , Ouyang Eva Y. , Stephan Douglas W.
Published: November 2009

By employing strategies based on frustrated Lewis pair chemistry, new routes to phosphino‐phosphonium cations and zwitterions have been developed. B(C6F5)3 is shown to react with H2 and P2tBu4 to effect heterolytic hydrogen activation yielding the phosphino‐phosphonium borate salt [(tBu2P)PHtBu2] [HB(C6F5)3] (1). Alternatively, alkenylphosphino‐phosphonium borate zwitterions are accessible by reaction of B(C6F5)3 and PhCCH with P2Ph4, P4Cy4, or P5Ph5 affording the species [(Ph2P)P(Ph)2C(Ph)C(H)B(C6F5)3] (2), [(P3Cy3)P(Cy)C(Ph)C(H)B(C6F5)3] (3), and [(P4Ph4)P(Ph)C(Ph)C(H)B(C6F5)3] (4). A related phosphino‐phosphonium borate species—[(Ph4P4)P(Ph)C6F4B(F)(C6F5)2] (5) is also isolated from the thermolysis of B(C6F5)3 and P5Ph5.
Absolute configurations of DNA lesions determined by comparisons of experimental ECD and ORD spectra with DFT calculations
Authors: Ding Shuang , Kolbanovskiy Alexander , Durandin Alexander , Crean Conor , Shafirovich Vladimir , Broyde Suse , Geacintov Nicholas E.
Published: November 2009

The usefulness of modern density functional theory (DFT) methods is considered for establishing the absolute configurations of DNA lesions by comparisons of computed and experimentally measured optical rotatory dispersion (ORD) and electronic circular dichroism (ECD) spectra. Two rigid, structurally different DNA lesions (two spiroiminodihydantoin stereoisomers and four equine estrogen 4‐hydoxyequilenin—DNA stereoisomeric adducts) have been investigated. In all cases, the signs and shapes of the computed ORD spectra reproduced the experimentally measured ORD spectra, although the magnitudes of the computed and experimental ORD values do not coincide exactly. The computed ECD spectra also reproduced the shapes of the experimental ECD spectra rather well, but are blue‐shifted by 10–20 nm. Since the assignments of the absolute configurations of the DNA lesions studied based on computed and experimental ORD and ECD spectra are fully consistent with one another, the computational DFT method shows significant promise for determining the absolute configurations of DNA lesions. Establishing the stereochemistry of DNA lesions is highly useful for understanding their biological impact, especially when sufficient amounts of material are not available for other methods of structural characterization. Chirality 21:E231–E241, 2009. © 2009 Wiley‐Liss, Inc.
Dispersed phase holdup and slip velocity of phases in a pulsed packed column in conditions with and without mass transfer
Authors: Hokmabadi Farzad Torabi , Bahmanyar Hossein , Amanabadi Marzieh , Safdari Jaber
Published: November 2009

Dispersed phase holdup and slip velocity of phases were measured in a pilot plant pulsed packed column with a diameter of 76.2 mm for two different chemical systems in conditions with and without mass transfer. The effects of pulsation intensity, dispersed and continuous phases flow rates, interfacial tension and solute concentration on dispersed phase holdup and slip velocity of phases were investigated. A new empirical correlation in terms of the above‐mentioned parameters developed from the measurements is given for the prediction of slip velocity. The dispersed phase holdup was calculated by means of this correlation and very good agreement between calculated and experimental values was obtained.
Oral L‐arginine Supplementation in Acute Myocardial Infarction Therapy: A Meta‐analysis of Randomized Controlled Trials
Authors: Sun Tao , Zhou Wen‐bai , Luo Xin‐ping , Tang Yao‐liang , Shi Hai‐ming
Published: November 2009

Objective

The objective was to analyze completed trials assessing the effect of oral L‐arginine supplementation on clinical outcomes of patients with acute myocardial infarction (AMI).

Background

Prior trials suggest that oral L‐arginine administration improves endothelial function in patients with stable coronary artery disease (CAD). However, it is still unclear whether oral supplementation of L‐arginine has any effect on clinical outcomes in patients with unstable CAD, such as AMI.

Methods

We systematically searched PubMed, Cochrane Library, Embase, reviews, and reference lists of relevant articles. The search strategy paired the term “arginine” with the following: “coronary heart disease,” “myocardial infarction,” “cardiovascular disease,” “ischemia,” and “trial.” We conducted a meta‐analysis of randomized, placebo‐controlled L‐arginine supplementation trials that evaluated clinical outcomes in AMI patients. Two reviewers independently assessed the trials. Differences were resolved by consensus.

Results

Only 2 trials (927 participants) were included. None of the 2 studies showed a significant difference in event rate between the L‐arginine and placebo groups. In an overall pooled estimate, there was a 7% reduction in mortality in the L‐arginine treatment group (105/459, 22.9%) compared with the control group (111/455, 24.4%), which did not reach statistical significance (risk ratio [RR]: 0.93, 95% confidence interval [CI]: 0.74–1.17; P = 0.54).

Conclusion

Oral L‐arginine supplementation has no effect on the clinical outcomes of patients with AMI. Copyright © 2009 Wiley Periodicals, Inc.
A randomized trial of external beam radiotherapy versus cryoablation in patients with localized prostate cancer
Authors: Donnelly Bryan J. , Saliken John C. , Brasher Penelope M. A. , Ernst Scott D. , Rewcastle John C. , Lau Harold , Robinson John , Trpkov Kiril
Published: November 2009

BACKGROUND:

Localized prostate cancer can be treated several different ways, but head‐to‐head comparisons of treatments are infrequent. The authors of this report conducted a randomized, unblinded, noninferiority trial to compare cryoablation with external beam radiotherapy in these patients.

METHODS:

From December 1997 through February 2003, 244 men with newly diagnosed localized prostate cancer were assigned randomly to receive either cryoablation or radiotherapy (122 men in each arm). All received neoadjuvant antiandrogen therapy. The primary endpoint was disease progression at 36 months based on a trifecta definition: 1) radiologic evidence of metastatic disease, or 2) initiation of further antineoplastic therapy, or 3) biochemical failure. Two definitions of biochemical failure were used: 1) 2 consecutive rises in prostate‐specific antigen (PSA) with a final value >1.0 ng/mL, and 2) a rise above PSA nadir + 2 ng/mL. Secondary endpoints included overall survival, disease‐specific survival, and prostate biopsy at 36 months.

RESULTS:

The median follow‐up was 100 months. Disease progression at 36 months was observed in 23.9% (PSA nadir + 2 ng/mL, 17.1%) of men in the cryoablation arm and in 23.7% (PSA nadir + 2 ng/mL, 13.2%) of men in the radiotherapy arm. No difference in overall or disease‐specific survival were observed. At 36 months, more patients in the radiotherapy arm had a cancer‐positive biopsy (28.9%) compared with patients in the cryoablation arm (7.7%).

CONCLUSIONS:

The observed difference in disease progression at 36 months was small, 0.2%; however, because of the wide confidence interval, from −10.8% to 11.2%, it was not possible to rule out inferiority (defined a priori as a 10% difference). With longer term follow‐up, the trend favors cryoablation. Significantly fewer positive biopsies were documented after cryoablation than after radiotherapy. Cancer 2010. © 2010 American Cancer Society.
Diffusion from within a Spherical Body with Partially Blocked Surface: Diffusion through a Constant Surface Area
Authors: Amatore Christian , Oleinick Alexander I. , Svir Irina
Published: November 2009

Diffusion from spherical bodies has been a subject of interest since the earliest times of modern sciences and a few equivalent analytical formulations of the problem are taught in engineering textbooks dealing with cooling rates of hot spheres. However, all these former studies assume that the diffusing material is transferable to/from the surrounding space through the whole surface of the spherical body. Conversely, the development of nanoscience and the improved knowledge of microscopic biological events have evidenced that diffusion from spherical bodies is a ubiquitous problem. It often occurs in situations where the nanosphere surfaces are not isotropic and partly impermeable to diffusing materials. This work elaborates on this issue and theoretically establishes that—with some specific allowance—the basic analytical equation of diffusion from/to fully accessible spherical bodies may be used.
Copper‐Azide‐Thioarylazoimidazoles – Structure, Spectra, Redox Properties, Magnetism and Theoretical Interpretation
Authors: Bhunia Prasenjit , Banerjee Debasis , Datta Papia , Raghavaiah Pallepogu. , Slawin Alexandra M. Z. , Woollins John D. , Ribas Joan , Sinha Chittaranjan
Published: November 2009

Azido‐copper(II) and ‐copper(I) complexes of 1‐alkyl‐2‐[(o‐thioalkyl)phenylazo]imidazole (SRaaiNR′) have been prepared and studied. Complex 2 [Cu(SRaaiNR′)(μ1,1‐N3)(N3)]2 dimerises via end‐to‐end (μ1,3)‐N3 to form a tetrameric structure. Azido‐copper(I) complexes of the ligands are obtained as MeOH‐bridged dimers, [Cu(SRaaiNR′)(N3)(μ‐OHMe)]2 (3). The electronic spectra suggest that a small reorganisation energy (0.08 eV) is associated with the change in electronic configuration, structure and oxidation state from CuII to CuI. Redox interconversion, CuII ↔ CuI, [Cu(SMeaaiNMe)(μ‐N3)(N3)]2 (2a) ↔ [Cu(SMeaaiNMe)(N3)(μ‐OHCH3)]2 (3a), has been performed in one case. The tetranuclear complex shows ferromagnetic and antiferromagnetic interactions. The spectra, redox chemistry and magnetism are explained by DFT studies.
2,3,5,6‐Tetrafluoro‐p‐phenylenebis(phosphanes) – Preparation and Structure of an Electron‐Poor P–RF–P Linker
Authors: Orthaber Andreas , Belaj Ferdinand , Albering Jörg H. , Pietschnig Rudolf
Published: November 2009

A general synthetic access to functional 2,3,5,6‐tetrafluoro‐p‐phenylenebis(phosphanes) is presented, which should open the way to linear phosphorus‐based conjugated systems incorporating an electron‐deficient aryl moiety. 1,4‐Bis[bis(diethylamino)phosphanyl]‐2,3,5,6‐tetrafluorobenzeneand 1,4‐bis(dichlorophosphanyl)‐2,3,5,6‐tetrafluorobenzene have been synthesized in good yields and were characterized by spectroscopic methods and X‐ray crystallography.
Nucleophilic Reactivities of Primary and Secondary Amines in Acetonitrile
Authors: Kanzian Tanja , Nigst Tobias A. , Maier Andreas , Pichl Stefan , Mayr Herbert
Published: November 2009

The kinetics of the reactions of primary and secondary amines with benzhydrylium ions and quinone methides in acetonitrile have been studied under pseudo‐first‐order conditions (high excess of amines) by UV/Vis spectrophotometry. Generally, the plots of kobs versus amine concentration were linear, in line with a second‐order rate law. However, for some reactions of secondary amines with quinone methides, the plots of kobs versus amine concentration showed an upward curvature, which indicates rate‐limiting deprotonation of the initially formed adduct by a second molecule of amine. From the second‐order rate constants k2 for the attack on the electrophiles by the amines, the nucleophilicity parameters N and s for the amines were determined from the linear free energy relationship log k2 (20 °C) = s(N + E). The rates of the reactions of the amines with benzhydrylium ions are strongly affected by solvent polarity, in sharp contrast to the analogous reactions of other neutral nucleophiles.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
A Simple One‐Pot Synthesis of New Imidazol‐2‐yl‐1H‐quinolin‐2‐ones from the Direct Reaction of 2‐Chloroquinolin‐3‐carbaldehyde with Aromatic o‐Diamines
Authors: Abonia Rodrigo , Castillo Juan , Cuervo Paola , Insuasty Braulio , Quiroga Jairo , Ortíz Alejandro , Nogueras Manuel , Cobo Justo
Published: November 2009

An alternative and general one‐pot synthesis of a library of novel imidazol‐2‐yl‐1H‐quinolin‐2‐one derivatives was performed in 70 % aqueous acetic acid by the direct reaction of 2‐chloroquinolin‐3‐carbaldehyde with aromatic o‐diamines. Experiments showed that adding Amberlyst®‐15 (20 % w/w) to the reaction media increased both the speed of reaction as well as the yield of products. Both DFT theoretical calculations and X‐ray diffraction studies confirmed the proposed structures and the more stable conformation of the obtained products. Antitumor studies against sixty different cancer cell lines showed the potential of these kinds of compounds.
Regioselective Reductive Cross‐Coupling Reactions of Unsymmetrical Alkynes
Authors: Reichard Holly A. , McLaughlin Martin , Chen Ming Z. , Micalizio Glenn C.
Published: November 2009

The present Microreview summarizes our progress over the last few years in defining regioselective reductive cross‐coupling reactions of unsymmetrical alkynes with terminal‐ and internal alkynes, aldehydes, and imines. We begin with a brief historical perspective of metal‐mediated reductive dimerization reactions of aromatic alkynes and discuss the challenges associated with “crossed” versions of this mode of reactivity. Next, a collection of available methods that allow for regioselective reductive cross‐coupling of internal alkynes with terminal and internal alkynes, aldehydes, and imines is summarized. After an examination of the requirements for regioselectivity in these cases, the logic behind our design of alkoxide‐directed titanium‐mediated reductive cross‐coupling reactions is presented. A nomenclature is introduced to delineate the presumed mechanistic origin of regioselection associated with each reaction design, and a presentation of alkoxide‐directed regioselective reductive cross‐coupling reactions of alkynes follows. Throughout, principal issues related to reactivity and selectivity are discussed to assess scope and limitations of available methods and to describe the broad challenges that exist for defining complex fragment union reactions based on reductive cross‐coupling chemistry.
Triassic palaeogeography and fluvial dispersal across the northwest European Basins
Authors: McKie Tom , Williams Brian
Published: November 2009

Triassic dryland fluvial systems occur infilling extensional and post‐rift basins across northwest Europe. These systems were deposited by streams draining off the major basin margin catchments of Greenland, Fennoscandia, the Scottish Highlands and the remnant Variscan mountains. Fluvial drainage was dominantly endorheic in character, and terminated in playa, aeolian dune, sabkha or marsh settings. Whilst the ambient basin climate fluctuated through varying levels of aridity and humidity, the dispersal of sand into these basins was critically dependant on catchment run‐off from the major, basin flanking regions. In the Early Triassic the Tethyan monsoon drove seasonal precipitation over the Variscan mountains which transported sediment northward into arid dune fields and playa. In addition, far‐travelled fluvial systems supplied sediment from distant, wetter catchments. Through the Middle and Late Triassic the effects of the Tethyan monsoon apparently weakened, and sand‐prone fluvial systems draining off the Variscan mountains were more limited in areal extent, but expanded during pluvial episodes. However, Greenland and Fennoscandia maintained sediment supply from the north, with perennial run‐off from Fennoscandia able to maintain marshes and levels of vegetation cover not encountered elsewhere in the region and to episodically drive major exorheic drainage systems into the Tethys Sea. Published climatic simulations are consistent with these observations, which indicate that Greenland, and particularly Fennoscandia, had precipitation levels higher than the regions to the south with a positive precipitation: evaporation balance. Copyright © 2009 John Wiley & Sons, Ltd.
Photophysical Processes in ‘Supramolecular Balls’ Formed by Lanthanide Chloride with 2,2′‐Bipyridine
Authors: Puntus Lada N.
Published: November 2009

The europium complex [EuCl2(bpy)2(H2O)2]Cl⋅1.25 C2H6O⋅0.37 H2O, where bpy is 2,2′‐bipyridine, was synthesized and investigated with the aim to relate its molecular geometry and crystal packing to the efficiency of energy‐transfer processes. The presence of H‐bonds between noncoordinated Cl− ions and coordinated H2O molecules leads to the formation of discrete trimers assembled by a number of CH⋅⋅⋅Cl and stacking interactions into ‘supramolecular balls’ which contain Cl− ions and solvate molecules (H2O and EtOH). The additional stabilization of the complex is due to intramolecular N⋅⋅⋅C interactions between two bpy ligands that causes some shortening of the EuN bonds. Deciphering the luminescence properties of the Eu complex was performed under consideration of both the composition of the inner coordination sphere and the peculiarities of the crystal packing. The influence of the latter and the bpy orientation on the energy of the ligand→Eu charge‐transfer state (LMCT) was established, and an additional excited state induced by the π‐stacking interaction (SICT) was identified.