bluuebunny/crossref_metadata_2025 huggingface dataset:
The Protonated Guanine–Cytosine Base Pair
Authors: Wang Hongyan , Zhang Jun D. , Schaefer Henry F.
Published: December 2009

Protonated base pairs were recently implicated in the context of DNA proton transfer and charge migration. The effects of protonating different sites of the guanine–cytosine (GC) base pair are studied here by using the DZP++ B3LYP density functional method. Optimized structures for the protonated GC base pair are compared with those of parent GC and the neutral hydrogenated GC radical (GCH). Proton and hydrogen‐atom additions significantly disturb the structure of the GC base pair. However, the structural perturbations arising from protonation are often less than those arising from hydrogenation of GC. Protonation of the GC base pair causes significant strengthening of the interstrand hydrogen bonds and a concomitant increase in the base dissociation energies. The adiabatic ionization potentials (AIPs), vertical ionization potentials (VIPs), and proton affinities (PAs) for the different protonation sites of the GC base pair are predicted. The N7 site of guanine is the preferred site for protonation of the GC base pair.
Multi‐Colour Electroluminescence of Dendronic Antennae Containing Pyrenes as Light Harvesters
Authors: Giovanella Umberto , Mróz Wojciech , Foggi Paolo , Fabbrizzi Pierangelo , Cicchi Stefano , Botta Chiara
Published: December 2009

Dendronic antennae systems containing pyrene units as energy donors and a styrylpyridinium derivative as energy acceptor show efficient energy transfer from the green‐emitting pyrene excimer to the red‐emitting acceptor. For the third dendron generation the effective screening of the pyrene units on the acceptor provides thin films showing bright red emission. Single‐layer light‐emitting diodes prepared by properly balancing the dendrons and donor units concentration in polyvinylcarbazole show electroluminescence from the blue, green and red components of the monomeric donor, the donor excimer and the acceptor when excitons are generated in the polymer and subsequently transferred to the molecules by resonant energy transfer.
Mesoscale Surface Patterning of a Laterally‐Grafted Rod Amphiphile: Rings And Fibers
Authors: Liu Libin , Kim Jung‐Keun , Lee Myongsoo
Published: December 2009

An aromatic amphiphilic molecule based on branched oligo(ethylene oxide) was synthesized. Evaporation‐driven ring formation and Langmuir–Blodgett films are investigated by utilizing this rigid–flexible block molecule. The size of the rings is strongly dependent on the solvent evaporation rate and the concentration of the molecule. In case of fast evaporation, volcano‐like rings are formed by evaporating solution of high concentration. Perfectly symmetrical rings with diameters in the range of 2–6 μm are obtained by evaporating solution of low concentration. The formation mechanism of the ring is briefly discussed. The molecule at the air–water interface exhibits excellent amphiphilic properties. Upon transferring the monolayer onto solid substrates, AFM revealed the formation of fine and long, straight fibers. By combining the data obtained from the isotherms, AFM, water contact angle measurements, and UV/Vis and fluorescence spectra, the fibers are suggested to be formed by π–π stacking interaction of the aromatic rod segments as the oligo(ethylene oxide) branches are submerged in the water subphase upon compression. The fiber formation is associated with the transformation of the aromatic rod segments from the face‐on conformation to the edge‐on conformation.
Is mindfulness‐based therapy an effective intervention for obsessive–intrusive thoughts: a case series
Authors: Wilkinson‐Tough Megan , Bocci Laura , Thorne Kirsty , Herlihy Jane
Published: December 2009

Despite the efficacy of cognitive‐behavioural interventions in improving the experience of obsessions and compulsions, some people do not benefit from this approach. The present research uses a case series design to establish whether mindfulness‐based therapy could benefit those experiencing obsessive–intrusive thoughts by targeting thought–action fusion and thought suppression. Three participants received a relaxation control intervention followed by a six‐session mindfulness‐based intervention which emphasized daily practice. Following therapy all participants demonstrated reductions in Yale‐Brown Obsessive–Compulsive Scale scores to below clinical levels, with two participants maintaining this at follow‐up. Qualitative analysis of post‐therapy feedback suggested that mindfulness skills such as observation, awareness and acceptance were seen as helpful in managing thought–action fusion and suppression. Despite being limited by small participant numbers, these results suggest that mindfulness may be beneficial to some people experiencing intrusive unwanted thoughts and that further research could establish the possible efficacy of this approach in larger samples. Copyright © 2009 John Wiley & Sons, Ltd.

Key Practitioner Message:

• Preliminary evidence is provided for the use of mindfulness‐based therapy with obsessive intrusive thoughts.

• Mindfulness processes may be useful in the management of thought‐action fusion and thought suppression.
Self‐concept and attributions about other women in women with a history of childhood sexual abuse
Authors: McAlpine Susan J. , Shanks Allison
Published: December 2009

Self‐concept literature and literature on childhood sexual abuse (CSA) suggests that women with a history of CSA may have particular ways of perceiving themselves, which, as well as impacting upon relationships within their everyday lives, may also have implications for therapy; whether this is on an individual basis or within a group. This research investigated self‐concept and attributions about other women using an adapted version of the self‐concept sorting task. Three groups of women were compared: women with a history of CSA, women experiencing depressed mood but without a history of CSA and a healthy non‐clinical comparison group of hospital staff. To some extent the current findings supported previous studies indicating that women attempting to cope with the consequences of a history of CSA have a negative self‐concept. However, there was evidence to suggest that certain self‐aspects are protective or protected. Similarly, there is some support for previous evidence of difficult relationships with mothers. Possible explanations for these findings were discussed and areas for future research suggested. Copyright © 2009 John Wiley & Sons, Ltd.

Key Practitioner Massage:

• Although women with a history of CSA and depression have a negative view of themselves in comparison to a non‐clinical group, there is no qualitative difference between these two groups.

• Nor do women with a history of CSA have a more negative view of other women in general than women who are depressed.

• Therefore, being aware of the likelihood that an individual may preceive herself, but not other women negatively, a therapist may use therapy to actively increase awareness and address this issue.
Psychopathology and well‐being in civilian survivors of war seeking treatment: a follow‐up study
Authors: Morina Nexhmedin , Rushiti Feride , Salihu Mimoza , Ford Julian D.
Published: December 2009

The goal of the current study was to examine types of exposure to traumatic events and affective and anxiety disorders of 81 civilian war survivors seeking treatment for war‐related stress almost one decade following the war in the area of former conflict. Furthermore, the study investigated changes in symptoms of mental health and in well‐being amongst these individuals during a treatment period of 6 months. The results indicated that civilian war survivors seeking treatment reported multiple war‐related traumatic events and high levels of psychiatric morbidity. Individuals assessed at follow‐up (n = 67) reported no change in post‐traumatic stress symptoms or psychological well‐being, but improvement in symptoms of depression, overall psychiatric distress and quality of life. The only significant difference between participants classified as achieving clinically significant improvement as compared with those who did not achieve such change was in less symptom severity of depression, post‐traumatic stress, general distress and higher psychological well‐being at the time of first assessment. Neither the assessment of initial diagnoses nor war or post‐war trauma types emerged as significantly different amongst the two groups. Copyright © 2009 John Wiley & Sons, Ltd.

Key Practitioner Message:

• Civilian survivors of war seeking treatment report high levels of psychiatric morbidity.

• Treatment for survivors of war may require adaptations to evidence‐based treatments based on their culture and life circumstances in order to recover from PTSD and experience general emotional relief.
Disruption tolerant networking by Smart Caching
Authors: Goebbels Stephan
Published: December 2009

Future mobile radio networks will aim at achieving ‘broadband access for all’, anywhere. The performance of a radio network vitally depends on the characteristics of the transmission path between the user terminal and the access point and the degree of network coverage. In urban areas, full broadband radio coverage is difficult to provide, causing a high variation in the link quality and making broadband services hard to realize. In rural regions, massive deployment costs prevent a full broadband coverage. Most of the time users have to settle for UMTS‐like wide area networks. For mobile users accessing services, such as video streaming, which require continuous broadband connectivity, it virtually results in intermittent network connectivity. The frequent disruption of the broadband link and its replacement with no or only low‐performance connections is a problem that should be addressed. This article introduces a new technique called Smart Caching (SC), which is able to mitigate variations in the network performance so that non‐real‐time and non‐interactive services' quality is substantially improved.

SC supports pre‐fetching from a server and buffering data at the edge of the core network, in the so‐called Smart Cache. It transmits data with extremely high speed to be buffered in the mobile terminal when it is in the service range of an access point. This allows for the provisioning of data‐intensive services even in the case of patchy wireless broadband network coverage and intermittent connectivity.

The performance of the SC service is evaluated with two different sophisticated queuing models, both based on the Markov arrival process. The benefit of the new technique is discussed and dimensioning issues are outlined. Furthermore, a comparison with legacy network setups is given. Copyright © 2009 John Wiley & Sons, Ltd.
The efficacy of monthly administration of darbepoetin alfa in Saudi hemodialysis patients
Authors: Alsaran Khalid , Sabry Alaa , Abdulghafour Mamdouh , Hji Mohammad
Published: December 2009

BACKGROUND

Erythropoiesis‐stimulating agents have improved the outcome and quality of life in patients with chronic kidney disease.

OBJECTIVE

We investigated the efficacy and safety of conversion of hemodialysis patients from epoetin beta to darbepoetin alfa administered once a month.

PATIENTS AND METHODS

The study included 26 patients. Their mean age was 47.0 6 17.13 years with a mean hemodialysis duration of 55.8 ± 14.0 months. The study was carried out in 2 consecutive phases of 12 weeks each. The mean initial dose of darbepoetin was 57 ± 10.0 mg biweekly. After maintaining target hemoglobin (Hgb) levels—(11–12 g/L)—with the biweekly injections, we shifted our patients to a once‐monthly dose schedule.

RESULTS

The mean weekly darbepoetin dose increased from 28.75 ± 4.2 mg during the biweekly phase to 38.5 ± 3.9 mg after switching to the monthly protocol (the mean conversion ratio changed from 309:1 to 256:1). The mean Hgb level was 10.81 ± .86 g/L at the start of the study and 10.86 ± .76 g/L at the end of 6 months.

CONCLUSION

Our experience with darbepoetin alfa reveals that it is effective and safe for the treatment of anemia in hemodialysis patients even at monthly dose intervals.
Peritoneal dialysis‐related peritonitis caused by Brucella melitensis
Authors: Unal Aydin , Sipahioglu Murat Hayri , Kavuncuoglu Feridun , Tokgoz Bulent , Oymak Oktay , Sumerkan Bulent , Utas Cengiz
Published: December 2009

Peritonitis is the most frequent complication in patients undergoing continuous ambulatory peritoneal dialysis (CAPD). CAPD‐related peritonitis caused by Brucella species has been reported in only three patients, in whom the Thenckhoff catheter was removed. We report two cases of CAPD‐related peritonitis caused by Brucella melitensis. In both patients, peritonitis accompanied systemic brucellosis and was successfully treated with antibiotics (rifampicin plus doxycycline for 6 weeks) without removal of the Tenckhoff catheter.
Cost analysis of continuous renal replacement and extended hemodialysis
Authors: Ahmed Ziauddin , Gilibert Stephanie , Krevolin Larry
Published: December 2009

BACKGROUND

Continuous renal replacement therapies (CRRTs) are now considered routinely in the treatment of patients with acute kidney injury (AKI) in the intensive care (ICU) setting. In search of the most effective modality, cost becomes important.

METHODS

Of the various modalities utilizing convection, diffusion, or a combination of the two, continuous venovenous hemodiafiltration (CVVHDF) and extended hemodialysis procedures (including sustained low‐efficiency dialysis [SLED]) are the most common in the United States; both have been noted to be effective in delivering an adequate dialysis dose. This study compared the costs of these two therapies in two Philadelphia teaching hospitals.

RESULTS

The cost for delivery of 24 hours of CVVHDF using the Gambro‐Prisma machine was found to be $1,602 versus $423 for 12 hours of SLED therapy with the Fresenius 2008K machine. Twenty‐four hours of SLED would cost $797, and the cost can be decreased to $77 if the nursing‐to‐patient ratio is increased from 1:1 to 1:2.

CONCLUSIONS

Higher material costs were primarily responsible for the expense of CVVHDF. Given that the dose deliveries are similar, SLED remains the most cost‐effective option for delivering renal replacement in the ICU setting. These costs may not exactly mirror those of other institutions depending on the types of solutions used, the filters utilized, salary differences based on geographical location, and the intensity of CRRT delivered.
Timing of the administration of intravenous darbepoetin alfa during the dialysis session: Does it impact efficacy?
Authors: Rottembourg Jacques , Kpade Floride , Dansaert Aurélie , Chenuc Gaelle
Published: December 2009

BACKGROUND

Darbepoetin alfa (DA) is an erythropoietin‐stimulating agent (ESA) preferably administered through intravenous (IV) route in hemodialysis (HD) patients. Although some in vitro studies suggest the possibility of partial adsorption of ESAs in dialysis membranes (Mb) and lines, these data are not clinically confirmed.

METHODS

This 12‐month, prospective, single‐center cross‐over study assessed the impact of the time of IV DA injection during HD on hemoglobin (Hgb) level and ESA dosing. A total of 90 HD patients received IV DA once every other week (Q2W), delivered at 2 possible time points: the middle or end of the HD session. After 6 months, the injection time point was crossed over to the other timing modality for another 6 months.

RESULTS

Demographics for both groups of patients were similar. Mean Hgb level remained stable from baseline to month 6 (not significant) for both timing modality groups. The same was observed for DA dose. Hemodialysis session parameters, nutritional status, and Kt/V were similar and stable during the study. Mean transferrin saturation was 44% and serum ferritin was $100 mg/L in more than 92% of patients. Iron supplementation remained unchanged and there were no blood transfusions during the study.

CONCLUSIONS

Q2W DA maintained target Hgb concentrations. The lack of difference in Hgb levels and DA dosing between the 2 injection timings suggests a lack of clinically significant adsorption/interaction between DA and dialysis Mb/lines. Therefore, timing of IV DA administration can be flexible and adapted to the routine practice of each local dialysis unit.
Developmental experience alters information coding in auditory midbrain and forebrain neurons
Authors: Woolley Sarah M.N. , Hauber Mark E. , Theunissen Frederic E.
Published: December 2009

In songbirds, species identity and developmental experience shape vocal behavior and behavioral responses to vocalizations. The interaction of species identity and developmental experience may also shape the coding properties of sensory neurons. We tested whether responses of auditory midbrain and forebrain neurons to songs differed between species and between groups of conspecific birds with different developmental exposure to song. We also compared responses of individual neurons to conspecific and heterospecific songs. Zebra and Bengalese finches that were raised and tutored by conspecific birds, and zebra finches that were cross‐tutored by Bengalese finches were studied. Single‐unit responses to zebra and Bengalese finch songs were recorded and analyzed by calculating mutual information (MI), response reliability, mean spike rate, fluctuations in time‐varying spike rate, distributions of time‐varying spike rates, and neural discrimination of individual songs. MI quantifies a response's capacity to encode information about a stimulus. In midbrain and forebrain neurons, MI was significantly higher in normal zebra finch neurons than in Bengalese finch and cross‐tutored zebra finch neurons, but not between Bengalese finch and cross‐tutored zebra finch neurons. Information rate differences were largely due to spike rate differences. MI did not differ between responses to conspecific and heterospecific songs. Therefore, neurons from normal zebra finches encoded more information about songs than did neurons from other birds, but conspecific and heterospecific songs were encoded equally. Neural discrimination of songs and MI were highly correlated. Results demonstrate that developmental exposure to vocalizations shapes the information coding properties of songbird auditory neurons. © 2009 Wiley Periodicals, Inc. Develop Neurobiol 70: 235–252, 2010.
Controls on dissolved organic matter concentrations in soils and streams from a forested wetland and sloping bog in southeast Alaska
Authors: D'Amore David V. , Fellman Jason B. , Edwards Richard T. , Hood Eran
Published: December 2009

Understanding the sources and removal mechanisms for dissolved organic matter (DOM) in soils is critical to determining the importance of peatlands in influencing streamwater DOM concentrations. Soil saturation and soil temperature are the primary factors that influence DOM cycling in soils, but the relationships among these factors vary by soil type and climate. Despite the extent of peatlands that occur within Pacific coastal temperate rainforest (CTR) watersheds, there is little information describing how DOM storage and export patterns are related to soil saturation and temperature in the region. We measured soil water tables, soil temperatures and redox potential and compared these measurements to fluctuations in dissolved organic carbon (DOC) and nitrogen (DON) concentrations in a forested wetland and sloping bog in southeast Alaska to address this key information gap. DOC concentrations ranged from 5 to 140 mg C l−1 in wetland soils, 11 to 46 mg C l−1 in streams, and varied greatly in response to changes in water table, redox potential and soil temperature. Similarly, DON concentrations ranged from 0·03 to 2·4 mg N l−1 in wetland soils, 0·2 to 0·6 mg N l−1 in streams and concentrations also reflected seasonal changes in physical measures. Depth to water table and soil temperature were significant factors related to the concentration of DOC in forested wetland soils and streams, while soil temperature was a significant factor that influenced stream DOC and DON concentrations. Comparing soil solution and stream DOM concentrations indicated that N is retained in bogs, while both dilution and biotic/abiotic retention mechanisms control DOM export in forested wetlands. The relationships among soil saturation, temperature and concentrations of DOC and DON provide preliminary models for estimating DOM fluxes from wetland soils in the CTR. Furthermore, these results can help calibrate regional watershed carbon flux models to predict the potential impacts of climate shifts and management activities on future wetland soil and stream DOM concentrations in CTR watersheds. Copyright © 2009 John Wiley & Sons, Ltd.
iC3b‐opsonized apoptotic cells mediate a distinct anti‐inflammatory response and transcriptional NF‐κB‐dependent blockade
Authors: Amarilyo Gil , Verbovetski Inna , Atallah Mizhir , Grau Amir , Wiser Giora , Gil Oranit , Ben‐Neriah Ynon , Mevorach Dror
Published: December 2009

In recent years, it has become apparent that the removal of apoptotic cells by macrophages and DC is not only noninflammatory, but also immune‐inhibitory, in most although not all circumstances. Complement may be involved in the uptake of apoptotic cells via direct binding of bridging factors in some physiological circumstances, by opsonization and engagement of the complement receptors. In the current study, we use a complement‐dependent system of apoptotic cell clearance by human‐derived macrophages and DC. Using a luciferase reporter gene and measuring immune response to non‐opsonic zymosan, we show that iC3b‐apoptotic cells induce NF‐κB inhibition in response to zymosan and LPS at the nuclear translocation, transcriptional and post‐transcriptional levels, leading to profound inhibition of proinflammatory cytokines. In addition, interaction with iC3b‐opsonized apoptotic cells is characterized by macrophage secretion of IL‐10 and lack of TGF‐β secretion. In conclusion, in cells with iC3b receptors, opsonized apoptotic cells mediate a distinct anti‐inflammatory response and transcriptional NF‐κB‐dependent blockage.
Functional analysis of the CD300e receptor in human monocytes and myeloid dendritic cells
Authors: Brckalo Tamara , Calzetti Federica , Pérez‐Cabezas Begoña , Borràs Francesc E. , Cassatella Marco A. , López‐Botet Miguel
Published: December 2009

The CD300e surface molecule, originally termed immune receptor expressed by myeloid cells (IREM)‐2, was reported to associate with the DNAX‐activating protein (DAP) 12 adaptor in co‐transfected cells, and is capable of signaling. In the present report, we investigated in detail the function of CD300e in monocytes and myeloid DC (mDC) freshly isolated from peripheral blood of normal blood donors. Upon engagement by an agonistic mAb, CD300e triggered an intracellular calcium mobilization and superoxide anion O production in monocytes. Activation via CD300e provided survival signals that prevented monocyte and mDC apoptosis, triggered the production of pro‐inflammatory cytokines and upregulated the expression of cell surface co‐stimulatory molecules in both cell types. Moreover, CD300e activation of mDC enhanced the alloreactive response of naive T cells. Overall, our data formally support the notion that CD300e functions as an activating receptor capable of regulating the innate immune response in myeloid cells.
In vivo depletion of CD4+FOXP3+ Treg cells by the PC61 anti‐CD25 monoclonal antibody is mediated by FcγRIII+ phagocytes
Authors: Setiady Yulius Y. , Coccia Jennifer A. , Park Peter U.
Published: December 2009

Depletion of CD4+CD25+FoxP3+ Treg using PC61 mAb (anti‐murine CD25 rat IgG1) is widely used to characterize Treg function in vivo. However, the mechanism of Treg depletion remains largely unknown. Herein, we report the PC61 mAb's mechanism of action. In peripheral blood, a single injection of PC61 mAb eliminated ∼70% of CD4+FoxP3+ cells with the remaining Treg expressing low or no CD25. Functional blockade of Fcγ receptors with 2.4G2 mAb significantly inhibited PC61 mAb activity. Furthermore, Fcγ receptor (FcγR)III−/− mice were resistant to Treg depletion. FcγRIII is expressed on immune cells including NK cells and macrophages that are the major effector cells for Ab‐dependent‐cellular‐cytotoxicity and Ab‐dependent‐cellular‐phagocytosis, respectively. Depletion of NK cells had no effect, whereas depletion of phagocytes, including macrophages, by clodronate liposome significantly inhibited Treg depletion. Furthermore, in vitro, PC61 mAb can mediate Ab‐dependent‐cellular‐phagocytosis of CD25+ cells by WT or FcγRIIB−/−, but not FcγRIII−/−, macrophages. Altogether these data demonstrate the critical role of FcγRIII+ phagocytes in mediating Treg depletion by PC61 mAb. This finding may be useful in guiding the development of human Treg targeting therapy.
The effect of placental malaria infection on cord blood and maternal immunoregulatory responses at birth
Authors: Flanagan Katie L. , Halliday Alice , Burl Sarah , Landgraf Katja , Jagne Ya Jankey , Noho‐Konteh Fatou , Townend John , Miles David J. C. , van der Sande Marianne , Whittle Hilton , Rowland‐Jones Sarah
Published: December 2009

Placental malaria (PM), a frequent infection of pregnancy, provides an ideal opportunity to investigate the impact on immune development of exposure of the foetal immune system to foreign Ag. We investigated the effect of PM on the regulatory phenotype and function of cord blood cells from healthy Gambian newborns and peripheral blood cells from their mothers, and analyzed for effects on the balance between regulatory and effector responses. Using the gold standard for classifying PM we further distinguished between resolved infection and acute or chronic PM active at the time of delivery. We show that exposure to malarial Ag in utero results in the expansion of malaria‐specific FOXP3+ Treg and more generalized FOXP3+ CD4+ Treg in chronic and resolved PM, alongside increased Th1 pro‐inflammatory responses (IFN‐γ, TNF‐α, IFN‐γ:IL‐10) in resolved PM infection only. These observations demonstrate a clear effect of exposure to malarial Ag in foetal life on the immune environment at birth, with a regulatory response dominating in the newborns with ongoing chronic PM, while those with resolved infection produce both regulatory and inflammatory responses. The findings might explain some of the adverse effects on the health of babies born to women with PM.
Critical role of lipid rafts in CD154‐mediated T cell signaling
Authors: El Fakhry Youssef , Alturaihi Haydar , Diallo Djibril , Merhi Yehye , Mourad Walid
Published: December 2009

Although signal pathways triggered via the CD40 molecule are well characterized, those induced via CD154 are less known. This study demonstrates that engagement of CD154 in Jurkat D1.1 cells with soluble CD40 leads to PKC α and δ activation, calcium mobilization, and phosphorylation of the Map kinases ERK1/2 and p38. Such response is accompanied by significant recruitment of CD154 into lipid rafts. Disruption of lipid rafts integrity with nystatin or methyl β‐cyclodextrin abrogated PKCα PKCδ and p38 phosphorylation, but had no effect on ERK1/2 phosphorylation. Inhibition of PKC activation completely abolished p38 phosphorylation but had no effect on ERK1/2 phosphorylation, suggesting that localization of CD154 within lipid rafts is an absolute requirement for CD154‐induced PKCα‐ and PKCδ‐dependent p38 phosphorylation. Furthermore, CD154 acts as co‐stimulator for the production of IL‐2 in an APC‐superantigen‐T‐cell activation model. The results obtained demonstrate for the first time, that lipid rafts are of immunological relevance for CD154‐triggered signals, and reinforce the importance of CD154 in T‐cell activation.
In vivo tumor cell rejection induced by NK cell inhibitory receptor blockade: Maintained tolerance to normal cells even in the presence of IL‐2
Authors: Vahlne Gustaf , Lindholm Katja , Meier Anders , Wickström Stina , Lakshmikanth Tadepally , Brennan Frank , Wilken Michael , Nielsen Rikke , Romagné François , Wagtmann Nicolai R. , Kärre Klas , Johansson Maria H.
Published: December 2009

Missing‐self‐reactivity can be mimicked by blocking self‐specific inhibitory receptors on NK cells, leading to increased rejection of syngeneic tumor cells. Using a mouse model, we investigated whether Ab‐mediated blocking of inhibitory receptors, to a degree where NK cells rejected syngeneic tumor cells, would still allow self‐tolerance toward normal syngeneic cells. Ly49C/I inhibitory receptors on C57BL/6 (H‐2b) NK cells were blocked with F(ab')2 fragments of the mAb 5E6. Inhibitory receptor blockade in vivo caused rejection of i.v. inoculated fluorescence‐labeled syngeneic lymphoma line cells but not of syngeneic spleen cells, BM cells or lymphoblasts. The selective rejection of tumor cells was NK cell‐dependent and specifically induced by Ly49C/I blockade. Moreover, selective tumor rejection was maintained after treatment with 5E6 F(ab')2 for 9 wk, arguing against the induction of NK cell anergy or autoreactivity during this time. Combination therapy using 5E6 F(ab')2 together with high dose IL‐2 treatment further increased lymphoma cell rejection. In addition, combination therapy reduced growth of melanoma cell line tumors established by s.c. inoculation 3 days before start of treatment. Our results demonstrate that inhibitory receptor blockade does not result in attack on normal cells, despite potent reactivity against MHC class I‐expressing tumors.
DNA vaccination with T‐cell epitopes encoded within Ab molecules induces high‐avidity anti‐tumor CD8+ T cells
Authors: Pudney Victoria A. , Metheringham Rachael L. , Gunn Barbara , Spendlove Ian , Ramage Judith M. , Durrant Lindy G.
Published: December 2009

Stimulation of high‐avidity CTL responses is essential for effective anti‐tumor and anti‐viral vaccines. In this study we have demonstrated that a DNA vaccine incorporating CTL epitopes within an Ab molecule results in high‐avidity T‐cell responses to both foreign and self epitopes. The avidity and frequency was superior to peptide, peptide‐pulsed DC vaccines or a DNA vaccine incorporating the epitope within the native Ag. The DNA Ab vaccine was superior to an identical protein vaccine that can only cross‐present, indicating a role for direct presentation by the DNA vaccine. However, the avidity of CTL responses was significantly reduced in Fc receptor γ knockout mice or if the Fc region was removed suggesting that cross presentation of Ag via Fc receptor was also important in the induction of high‐avidity CTL. These results suggest that generation of high‐avidity CTL responses by the DNA vaccine is related to its ability to both directly present and cross‐present the epitope. High‐avidity responses were capable of efficient anti‐tumor activity in vitro and in vivo. This study demonstrates a vaccine strategy to generate high‐avidity CTL responses that can be used in anti‐tumor and anti‐viral vaccine settings.
S1P3 confers differential S1P‐induced migration by autoreactive and non‐autoreactive immature B cells and is required for normal B‐cell development
Authors: Donovan Erin E. , Pelanda Roberta , Torres Raul M.
Published: December 2009

During B‐cell development, immature B‐cell fate is determined by whether the BCR is engaged in the bone marrow. Immature B cells that are non‐autoreactive continue maturation and emigrate from the marrow, whereas autoreactive immature B cells remain and are tolerized. However, the microenvironment where these events occur and the chemoattractants responsible for immature B‐cell trafficking within and out of the bone marrow remain largely undefined. Sphingosine 1‐phosphate (S1P) is a chemoattractant that directs lymphocyte trafficking and thymocyte egress and in this study we investigated whether S1P contributes to B‐cell development, egress and positioning within the bone marrow. Our findings show that immature B cells are chemotactic toward S1P but that this response is dependent on Ag receptor specificity: non‐autoreactive, but not autoreactive, immature B cells migrate toward S1P and are shown to require S1P3 receptor for this response. Despite this response, S1P3 is shown not to facilitate immature B‐cell egress but is required for normal B‐cell development including the positioning of transitional B cells within bone marrow sinusoids. These data indicate that S1P3 signaling directs immature B cells to a bone marrow microenvironment important for both tolerance induction and maturation.
Differential regulation of iron homeostasis during human macrophage polarized activation
Authors: Recalcati Stefania , Locati Massimo , Marini Agnese , Santambrogio Paolo , Zaninotto Federica , De Pizzol Maria , Zammataro Luca , Girelli Domenico , Cairo Gaetano
Published: December 2009

Iron metabolism in inflammation has been mostly characterized in macrophages exposed to pathogens or inflammatory conditions, mimicked by the combined action of LPS and IFN‐γ (M1 polarization). However, macrophages can undergo an alternative type of activation stimulated by Th2 cytokines, and acquire a role in cell growth and tissue repair control (M2 polarization). We characterized the expression of genes related to iron homeostasis in fully differentiated unpolarized (M0), M1 and M2 human macrophages. The molecular signature of the M1 macrophages showed changes in gene expression (ferroportin repression and H ferritin induction) that favour iron sequestration in the reticuloendothelial system, a hallmark of inflammatory disorders, whereas the M2 macrophages had an expression profile (ferroportin upregulation and the downregulation of H ferritin and heme oxygenase) that enhanced iron release. The conditioned media from M2 macrophages promoted cell proliferation more efficiently than those of M1 cells and the effect was blunted by iron chelation. The role of ferroportin‐mediated iron release was demonstrated by the absence of differences from the media of macrophages of a patient with loss of function ferroportin mutation. The distinct regulation of iron homeostasis in M2 macrophages provides insights into their role under pathophysiological conditions.
The A2aR adenosine receptor controls cytokine production in iNKT cells
Authors: Nowak Michael , Lynch Lydia , Yue Simon , Ohta Akio , Sitkovsky Michail , Balk Steven P. , Exley Mark. A.
Published: December 2009

The purine nucleoside adenosine is an important anti‐inflammatory molecule, inhibiting a variety of immune cells by adenosine receptor‐mediated mechanisms. Invariant NKT (iNKT) cells recognize glycolipids presented on CD1d molecules and produce vigorous amounts of cytokines upon activation, hence regulating immune reactions. The mechanisms polarizing their cytokine pattern are elusive. Previous studies demonstrated that adenosine can suppress IFN‐γ production by iNKT cells. We describe the expression of all four known adenosine receptors A1R, A2aR, A2bR and A3R on mouse iNKT cells. We show that IL‐4 production in primary mouse iNKT cells and a human iNKT line is efficiently inhibited by A2aR blockade with an inverse relation to IL‐4. These data are supported by A2aR‐deficient mice, which exhibit largely decreased levels of IL‐4, IL‐10 and TGF‐β concomitantly with an increase of IFN‐γ upon α‐galactosylceramide administration in vivo. While A2aR inhibits other lymphocyte populations, A2aR is required for the secretion of IL‐4 and IL‐10 by iNKT cells. These data suggest adenosine:A2aR‐mediated mechanisms can control the cytokine secretion pattern of iNKT cells.
Does TLR2 regulate intestinal inflammation?
Authors: Mowat Allan McI
Published: December 2009

There is almost no aspect of the immune response that is not regulated by TLR. Initially described as drivers of the innate immune response to pathogens, it is now clear that the TLR family can also influence most aspects of adaptive immunity, as well as determine how tissue cells interact with microbes in their environment. In particular, the intestine and its immune system must co‐exist with an enormous community of commensal bacteria and are also on constant alert against invading pathogens. Unsurprisingly, there is therefore great interest in how TLR might regulate physiological and pathological reactions in the gut. An article in this issue of the European Journal of Immunology addresses this question with some elegant experiments that indicate that TLR2 is not essential for the pathogenesis or T‐cell‐mediated regulation of different models of inflammatory bowel disease in mice.
Growing trend of CE at the omics level: The frontier of systems biology
Authors: Oh Eulsik , Hasan Md. Nabiul , Jamshed Muhammad , Park Soo Hyun , Hong Hye‐Min , Song Eun Joo , Yoo Young Sook
Published: December 2009

In a novel attempt to comprehend the complexity of life, systems biology has recently emerged as a state‐of‐the‐art approach for biological research in contrast to the reductionist approaches that have been used in molecular cell biology since the 1950s. Because a massive amount of information is required in many systems biology studies of life processes, we have increasingly come to depend on techniques that provide high‐throughput omics data. CE and CE coupled to MS have served as powerful analytical tools for providing qualitative and quantitative omics data. Recent systems biology studies have focused strongly on the diagnosis and treatment of diseases. The increasing number of clinical research papers on drug discovery and disease therapies reflects this growing interest among scientists. Since such clinical research reflects one of the ultimate purposes of bioscience, these trends will be sustained for a long time. Thus, this review mainly focuses on the application of CE and CE‐MS in diagnosis as well as on the latest CE methods developed. Furthermore, we outline the new challenges that arose in 2008 and later in elucidating the system‐level functions of the bioconstituents of living organisms.
Recent approaches for enhancing sensitivity in enantioseparations by CE
Authors: Sánchez‐Hernández Laura , García‐Ruiz Carmen , Luisa Marina María , Luis Crego Antonio
Published: December 2009

This article reviews the latest methodological and instrumental improvements for enhancing sensitivity in chiral analysis by CE. The review covers literature from March 2007 until May 2009, that is, the works published after the appearance of the latest review article on the same topic by Sánchez‐Hernández et al. [Electrophoresis 2008, 29, 237–251]. Off‐line and on‐line sample treatment techniques, on‐line sample preconcentration strategies based on electrophoretic and chromatographic principles, and alternative detection systems to the widely employed UV/Vis detection in CE are the most relevant approaches discussed for improving sensitivity. Microchip technologies are also included since they can open up great possibilities to achieve sensitive and fast enantiomeric separations.
Capillary and microchip electrophoresis in microdialysis: Recent applications
Authors: Guihen Elizabeth , O'Connor William T.
Published: December 2009

The theme of this review is to highlight the importance of microscale electrophoretic‐based separation systems in microdialysis (μD). The ability of CE and MCE to yield very rapid and highly efficient separations using just nanolitre volumes of microdialysate samples will also be discussed. Recent advances in this area will be highlighted, by illustration of some exciting new applications while the need for further innovation will be covered. The first section briefly introduces the concept of μD sampling coupled with electrophoresis‐based separation and the inherent advantages of this approach. The following section highlights some specific applications of CE separations in the detection of important biomarkers such as low‐molecular‐weight neurotransmitters, amino acids, and other molecules that are frequently encountered in μD. Various detection modes in CE are outlined and some of the advantages and drawbacks thereof are discussed. The last section introduces the concepts of micro‐total analysis systems and the coupling of MCE and μD. Some of the latest innovations will be illustrated. The concluding section reflects on the future of this important chemical alliance between μD and CE/MCE.
Recent developments in PDMS surface modification for microfluidic devices
Authors: Zhou Jinwen , Ellis Amanda Vera , Voelcker Nicolas Hans
Published: December 2009

PDMS is enjoying continued and ever increasing popularity as the material of choice for microfluidic devices due to its low cost, ease of fabrication, oxygen permeability and optical transparency. However, PDMS's hydrophobicity and fast hydrophobic recovery after surface hydrophilization, attributed to its low glass transition temperature of less than −120°C, negatively impacts on the performance of PDMS‐based microfluidic device components. This issue has spawned a flurry of research to devise longer lasting surface modifications of PDMS, with particular emphasis on microfluidic applications. This review will present recent research on surface modifications of PDMS using techniques ranging from metal layer coatings and layer‐by‐layer depositions to dynamic surfactant treatments and the adsorption of amphipathic proteins. We will also discuss significant advances that have been made with a broad palette of gas‐phase processing methods including plasma processing, sol–gel coatings and chemical vapor deposition. Finally, we will present examples of applications and future prospects of modified PDMS surfaces in microfluidics, in areas such as molecular separations, cell culture in microchannels and biomolecular detection via immunoassays.
Electrophoretic and electrochromatographic separation of proteins in capillaries: An update covering 2007–2009
Authors: El Rassi Ziad
Published: December 2009

This review article covers 3‐year period from 2007 to 2009 and is a continuation of the review article by V. Dolnik, [Electrophoresis 2008, 29, 143–156]. This article with 125 references describes recent developments in CE and CEC of proteins in capillary format and does not cover the developments of CE and CEC in microchip format, since Tran et al. review the microchip subject in this special issue. The present review article has four major topics including (i) the separation media, (ii) multidimensional separations, (iii) detection, and (iv) applications.
Residual‐based variational multiscale methods for laminar, transitional and turbulent variable‐density flow at low Mach number
Authors: Gravemeier Volker , Wall Wolfgang A.
Published: December 2009

In the present study, residual‐based variational multiscale methods are developed for and applied to variable‐density flow at low Mach number. In particular, two different formulations are considered in this study: a standard stabilized formulation featuring SUPG/PSG/grad‐div terms and a complete residual‐based variational multiscale formulation additionally containing cross‐ and Reynolds‐stress terms as well as subgrid‐scale velocity terms in the energy‐conservation equation. The proposed methods are tested for various laminar flow test cases as well as a test case at laminar via transitional to turbulent flow stages. Stable and accurate results are obtained for all numerical examples. Substantial differences in the results between the two approaches do not become notable until a high temperature gradient is applied and the flow reaches a turbulent flow stage. The more pronounced influence of adding subgrid‐scale velocity terms to the energy‐conservation equation on the results than adding analogous terms to the momentum‐conservation equation in this situation appears particularly noteworthy. Copyright © 2009 John Wiley & Sons, Ltd.
A fast universal solver for 1D continuous and discontinuous steady flows in rivers and pipes
Authors: Kerger François , Archambeau Pierre , Erpicum Sébastien , Dewals Benjamin J. , Pirotton Michel
Published: December 2009

Simulation of 1D steady flow covers a wide range of practical applications, such as rivers, pipes and hydraulic structures. Various flow patterns coexist in such situations: free surface flows (supercritical, subcritical and hydraulic jump), pressurized flows as well as mixed flows. As a result, development of a unified 1D model for all the situations of interest in civil engineering remains challenging. In this paper, a fast universal solver for 1D continuous and discontinuous steady flows in rivers and pipes is set up and assessed. Developments are initiated from an original unified mathematical model using the Saint‐Venant equations. Application of these equations, originally dedicated to free‐surface flow, is extended to pressurized flow by means of the Preissmann slot model. In particular, an original negative slot is developed in order to handle sub‐atmospheric pressurized flow. Next, the full unsteady model is simplified under the assumption of steadiness and reformulated into a single pseudo‐unsteady differential equation. The derived pseudo‐unsteady formulation aims at keeping the hyperbolic feature of the equation. Stability analysis of the differential equation suggests a unique splitting for the finite volume scheme whatever the flow conditions. The numerical scheme obtained is a universal Flux Vector Splitting which shows robustness and simplicity. Accuracy and performance of the new methodology is assessed by comparison with analytical and experimental results. Copyright © 2009 John Wiley & Sons, Ltd.
Nowcasting from disaggregates in the face of location shifts
Authors: Castle Jennifer L. , Hendry David F.
Published: December 2009

Given a need for nowcasting, we consider how nowcasts can best be achieved, the use and timing of information, including disaggregation over variables and common features, and the role of automatic model selection for nowcasting missing disaggregates. We focus on the impact of location shifts on nowcast failure and nowcasting during breaks, using impulse saturation, its relation to intercept correction, and to robust methods to avoid systematic nowcast failure. We propose a nowcasting strategy, building models of all N disaggregate series by automatic methods, forecasting every variable each period, then testing for shifts in available measures, switching to robust forecasts of missing series when breaks are detected. Copyright © 2009 John Wiley & Sons, Ltd.
The UK intranational business cycle
Authors: Artis Michael , Okubo Toshihiro
Published: December 2009

The paper uses annual data on real GDP for 12 UK regions and 12 manufacturing sectors to derive regional and regional/sectoral business cycles using a Hodrick–Prescott filter. The cohesion of the cycles is examined via cross‐correlations and comparisons made with the regional cycles for Japan, the USA and the euro area. The UK emerges as especially cohesive and efforts to explain the overall cross‐correlations of regional GDP are not very successful owing to the low variance of the explicand; when attention is turned to the sectoral/regional cycles, with their greater variance, it is possible to demonstrate that economic variables such as distance, dissimilarity in structure and level of output play a significant role in explaining the variance in the cross‐correlations. A significant feature of the cross‐correlations in relation to those of EU countries is that while they continue to provide support for the ‘UK idiosyncrasy’ they no longer do so as strongly as they did in earlier data samples. Copyright © 2009 John Wiley & Sons, Ltd.