bluuebunny/crossref_metadata_2025 huggingface dataset:
Deposition of two natural clays on a Pt surface using potentiostatic and spin-coating techniques: a comparative study
Authors: Issa A. A. , Al-Degs Y. S. , Al-Rabady N. A.
Published: October 2008

Two natural clays (kaolinite and montmorillonite) were deposited onto a platinum electrode surface using two deposition techniques and under different experimental variables. For both clays, the percentages of surface coverage (%θ) were optimized in the 75–96% range. A greater surface coverage was observed at higher temperatures for both clays, which confirms the endothermic nature of the deposition process. The maximum surface coverage (96%) was achieved for kaolinite. The surface coverage of kaolinite on a platinum electrode was constant for deposition times between 6 and 20 h. A surface coverage of 91% with montmorillonite particles was achieved. There was a very small increase in surface coverage by increasing the concentration of clay in the modified solution. The maximum surface coverage was observed under acidic conditions and smaller coverage values were reported for neutral and basic solutions. For both clays, a complete surface coverage for the electrode surface was achieved using the spin-coating technique. The experimental variables that affect the deposition of the clay, such as the stoichiometric ratio of clay/PVC and centrifugation speed and time, were studied and optimized to obtain full surface coverage. The spin-coating method achieved the required durability and stability for the modified-electrode. The characterization showed that the metallic surface chemistry of the platinum electrode was totally suppressed. Both modified electrodes were found to be useful for determination of Ag(I) ion with a detection limit as small as 1.00×10–10M. The analytical precision was also satisfactory (RSD <5.0%).
RAS oncogene suppression induces apoptosis followed by more differentiated and less myelosuppressive disease upon relapse of acute myeloid leukemia
Authors: Kim Won-Il , Matise Ilze , Diers Miechaleen D. , Largaespada David A.
Published: October 2008

To study the oncogenic role of the NRAS oncogene (NRASG12V) in the context of acute myeloid leukemia (AML), we used a Vav promoter–tetracycline transactivator (Vav-tTA)–driven repressible TRE-NRASG12V transgene system in Mll-AF9 knock-in mice developing AML. Conditional repression of NRASG12V expression greatly reduced peripheral white blood cell (WBC) counts in leukemia recipient mice and induced apoptosis in the transplanted AML cells correlated with reduced Ras/Erk signaling. After marked decrease of AML blast cells, myeloproliferative disease (MPD)–like AML relapsed characterized by cells that did not express NRASG12V. In comparison with primary AML, the MPD-like AML showed significantly reduced aggressiveness, reduced myelosuppression, and a more differentiated phenotype. We conclude that, in AML induced by an Mll-AF9 transgene, NRASG12V expression contributes to acute leukemia maintenance by suppressing apoptosis and reducing differentiation of leukemia cells. Moreover, NRASG12V oncogene has a cell nonautonomous role in suppressing erythropoiesis that results in the MPD-like AML show significantly reduced ability to induce anemia. Our results imply that targeting NRAS or RAS oncogene-activated pathways is a good therapeutic strategy for AML and attenuating aggressiveness of relapsed AML.
Impaired function of primitive hematopoietic cells in mice lacking the Mixed-Lineage-Leukemia homolog Mll5
Authors: Madan Vikas , Madan Babita , Brykczynska Urszula , Zilbermann Frédéric , Hogeveen Kevin , Döhner Konstanze , Döhner Hartmut , Weber Odile , Blum Carmen , Rodewald Hans-Reimer , Sassone-Corsi Paolo , Peters Antoine H. F. M. , Fehling Hans Jörg
Published: October 2008

The human Mixed-Lineage-Leukemia-5 (MLL5) gene is located in a genomic region frequently deleted in patients with myeloid malignancies and encodes a widely expressed nuclear protein most closely related to MLL1, a Trithorax transcriptional regulator with established involvement in leukemogenesis. Although the physiologic function of MLL5 is completely unknown, domain structure and homology to transcriptional regulators with histone methyltransferase activity suggest a role in epigenetic gene regulation. To investigate physiologic functions of Mll5, we have generated a knockout mouse mutant using Cre/loxP technology. Adult homozygous Mll5-deficient mice are obtained at reduced frequency because of postnatal lethality. Surviving animals display a variety of abnormalities, including male infertility, retarded growth, and defects in multiple hematopoietic lineages. Interestingly, Mll5−/− mice die of sublethal whole-body irradiation but can be rescued with wild-type bone marrow grafts. Flow cytometric ana-lysis, bone marrow reconstitution, and in vivo BrdU-labeling experiments reveal numerical, functional, and cell-cycle defects in the lineage-negative Sca-1+, Kit+ (LSK) population, which contains short- and long-term hematopoietic stem cells. Together, these in vivo findings establish several nonredundant functions for Mll5, including an essential role in regulating proliferation and functional integrity of hematopoietic stem/progenitor cells.
Serum amyloid A induces G-CSF expression and neutrophilia via Toll-like receptor 2
Authors: He Rong L. , Zhou Jian , Hanson Crystal Z. , Chen Jia , Cheng Ni , Ye Richard D.
Published: October 2008

The acute-phase protein serum amyloid A (SAA) is commonly considered a marker for inflammatory diseases; however, its precise role in inflammation and infection, which often result in neutrophilia, remains ambiguous. In this study, we demonstrate that SAA is a potent endogenous stimulator of granulocyte colony-stimulated factor (G-CSF), a principal cytokine-regulating granulocytosis. This effect of SAA is dependent on Toll-like receptor 2 (TLR2). Our data demonstrate that, in mouse macrophages, both G-CSF mRNA and protein were significantly increased after SAA stimulation. The induction of G-CSF was blocked by an anti-TLR2 antibody and markedly decreased in the TLR2-deficient macrophages. SAA stimulation results in the activation of nuclear factor–κB and binding activity to the CK-1 element of the G-CSF promoter region. In vitro reconstitution experiments also support that TLR2 mediates SAA-induced G-CSF expression. In addition, SAA-induced secretion of G-CSF was sensitive to heat and proteinase K treatment, yet insensitive to polymyxin B treatment, indicating that the induction is a direct effect of SAA. Finally, our in vivo studies confirmed that SAA treatment results in a significant increase in plasma G-CSF and neutrophilia, whereas these responses are ablated in G-CSF– or TLR2-deficient mice.
A functional folate receptor is induced during macrophage activation and can be used to target drugs to activated macrophages
Authors: Xia Wei , Hilgenbrink Andrew R. , Matteson Eric L. , Lockwood Michael B. , Cheng Ji-Xin , Low Philip S.
Published: October 2008

Previous work has demonstrated that a subset of macrophages expresses a folate receptor (FR) that can mediate internalization of folate-linked molecules, including imaging and therapeutic agents. To characterize this subset, macrophages were collected from peritoneal cavities of mice injected with saline, thioglycolate, zymosan, heat-killed or live bacteria, and cell-surface markers that coexpress with FR were identified. Virtually no F4/80+ peritoneal macrophages from saline-injected mice expressed FR, whereas numerous macrophages from mice injected with each inflammatory stimulus expressed FR. Examination of cell differentiation antigens that are up-regulated in FR+ macrophages revealed markers characteristic of an activated state (CD80, CD86, Ly-6C/G), whereas macrophages lacking these activation markers expressed few or no FR. FR+ macrophages also produced tumor necrosis factor-α (TNF-α) and reactive oxygen species, and production of reactive oxygen species correlated linearly with expression of FR. Synovial macrophages collected from arthritic patients were found to bind and internalize folate-linked dyes. Moreover, a folate-linked radioimaging agent was shown to image inflamed joints of rheumatoid arthritic patients. These results suggest that FR constitutes a marker for macrophage activation and that FR+ macrophages can be targeted with folate-linked drugs without promoting drug uptake by nonactivated macrophages. This trial was registered at www.clinicaltrials.gov as #NCT00588393.
Impaired apoptotic cell clearance in CGD due to altered macrophage programming is reversed by phosphatidylserine-dependent production of IL-4
Authors: Fernandez-Boyanapalli Ruby F. , Frasch S. Courtney , McPhillips Kathleen , Vandivier R. William , Harry Brian L. , Riches David W. H. , Henson Peter M. , Bratton Donna L.
Published: October 2008

Chronic granulomatous disease (CGD) is characterized by overexuberant inflammation and autoimmunity that are attributed to deficient anti-inflammatory signaling. Although regulation of these processes is complex, phosphatidylserine (PS)–dependent recognition and removal of apoptotic cells (efferocytosis) by phagocytes are potently anti-inflammatory. Since macrophage phenotype also plays a beneficial role in resolution of inflammation, we hypothesized that impaired efferocytosis in CGD due to macrophage skewing contributes to enhanced inflammation. Here we demonstrate that efferocytosis by macrophages from CGD (gp91phox−/−) mice was suppressed ex vivo and in vivo. Alternative activation with interleukin 4 (IL-4) normalized CGD macrophage efferocytosis, whereas classical activation by lipopolysaccharide (LPS) plus interferon γ (IFNγ) had no effect. Importantly, neutralization of IL-4 in wild-type macrophages reduced macrophage efferocytosis, demonstrating a central role for IL-4. This effect was shown to involve 12/15 lipoxygenase and activation of peroxisome-proliferator activated receptor γ (PPARγ). Finally, injection of PS (whose exposure is lacking on CGD apoptotic neutrophils) in vivo restored IL-4–dependent macrophage reprogramming and efferocytosis via a similar mechanism. Taken together, these findings support the hypothesis that impaired PS exposure on dying cells results in defective macrophage programming, with consequent efferocytic impairment and has important implications in understanding the underlying cause of enhanced inflammation in CGD.
PIAS3 negatively regulates RANKL-mediated osteoclastogenesis directly in osteoclast precursors and indirectly via osteoblasts
Authors: Hikata Tomohiro , Takaishi Hironari , Takito Jiro , Hakozaki Akihiro , Furukawa Mitsuru , Uchikawa Shinichi , Kimura Tokuhiro , Okada Yasunori , Matsumoto Masahito , Yoshimura Akihiko , Nishimura Riko , Reddy Sakamuri V. , Asahara Hiroshi , Toyama Yoshiaki
Published: October 2008

Cytokine signaling via various transcription factors regulates receptor activator of nuclear factor (NF)–κB ligand (RANKL)–mediated osteoclast differentiation from monocyte/macrophage lineage cells involved in propagation and resolution of inflammatory bone destruction. Protein inhibitor of activated STAT3 (PIAS3) was initially identified as a molecule that inhibits DNA binding of STAT3 and regulates many transcription factors through distinct mechanisms. To analyze PIAS3 function in osteoclasts in vivo, we have generated transgenic mice in which PIAS3 is specifically expressed in the osteoclast lineage using the tartrate-resistant acid phosphatase (TRAP) gene promoter. PIAS3 transgenic mice showed an osteopetrotic phenotype due to impairment of osteoclast differentiation. Overexpression of PIAS3 in RAW264.7 cells suppressed RANKL-induced osteoclastogenesis by inhibiting the expression of c-Fos and NFATc1. Interestingly, PIAS3 inhibits the transcriptional activity of microphthalmiaassociated transcription factor (MITF) independent of sumoylation. Down-regulation of PIAS3 markedly enhances RANKL-mediated osteoclastogenesis in RAW264.7 cells. Furthermore, overexpression of PIAS3 in mouse primary osteoblast (POB), down-regulates RANKL expression induced by interleukin-6 (IL-6) cytokine family, and inhibits osteoclast formation from bone marrow macrophages (BMMs) in vitro coculture system. Down-regulation of PIAS3 leads to the accelerated expression of RANKL in POB stimulated with IL-6 and soluble IL-6 receptor (sIL-6R). Taken together, our results clearly indicate that PIAS3 negatively regulates RANKL-mediated osteoclastogenesis directly in osteoclast precursors and indirectly via osteoblasts.
HSV ICP0 recruits USP7 to modulate TLR-mediated innate response
Authors: Daubeuf Sandrine , Singh Divyendu , Tan Yaohong , Liu Hongiu , Federoff Howard J. , Bowers William J. , Tolba Khaled
Published: October 2008

Pattern recognition receptors represent the first line of defense against invading pathogens. Herpes simplex virus (HSV) encodes multiple ligands detected by these receptors, yet persists in the majority of infected individuals indicating a breakdown in host defense against the virus. Here we identify a novel mechanism through which HSV immediate-early protein ICP0 inhibits TLR-dependent inflammatory response by blocking NF-κB and JNK activation downstream of TLR signal activation. This process depends on ICP0-mediated translocation of USP7 (HAUSP) from the nucleus to cytoplasm. We show that nuclear USP7 migrates to the cytoplasm in response to TLR engagement, a process that contributes to termination of TLR response. Cytoplasmic USP7 binds to and deubiquitinates TRAF6 and IKKγ, thus terminating TLR-mediated NF-κB and JNK activation. These findings suggest that USP7 is part of a negative feedback loop regulating TLR signaling and that ICP0 exploits this physiologic process to attenuate innate response to HSV. ICP0 inhibition of the TLR response serves to uncouple the innate and adaptive immune response, thereby playing a key role in HSV pathogenesis and persistence.
Mcl-1: the 1 in CLL
Authors: Gandhi Varsha , Balakrishnan Kumudha , Chen Lisa S.
Published: October 2008

Although Mcl-1 has been established as a survival and maintenance protein during in vitro incubations of primary CLL cells, in this issue of Blood, Pepper and colleagues further demonstrate the association of Mcl-1 with other prognostic factors and the role of this antiapoptotic protein in disease progression and outcome for patients with CLL.
R93W mutation in Orai1 causes impaired calcium influx in platelets
Authors: Bergmeier Wolfgang , Oh-hora Masatsugu , McCarl Christie-Ann , Roden R. Claire , Bray Paul F. , Feske Stefan
Published: October 2008

The intracellular Ca2+ concentration of many nonexcitable cells is regulated by calcium store release and store-operated calcium entry (SOCE). In platelets, STIM1 was recently identified as the main calcium sensor expressed in the endoplasmic reticulum. To evaluate the role of the SOC channel moiety, Orai1, in platelet SOCE, we generated mice expressing a mutated, inactive form of Orai1 in blood cells only (Orai1R93W). Platelets expressing Orai1R93W were characterized by markedly reduced SOCE and impaired agonist-induced increases in [Ca2+]i. Orai1R93W platelets showed reduced integrin activation and impaired degranulation when stimulated with low agonist concentrations under static conditions. This defect, however, did not significantly affect the ability of Orai1R93W platelets to aggregate or to adhere to collagen under arterial flow conditions ex vivo. In contrast, these adherent Orai1R93W platelets were defective in surface phosphatidylserine exposure, suggesting that Orai1 is crucial for the platelets' procoagulant response rather than for other Ca2+-dependent cellular responses.
Suppressing the tumor suppressor in CLL?
Authors: Pepper Chris
Published: October 2008

In this issue of Blood, Steele and colleagues present a series of elegant experiments that illuminate a p53 transcription-independent mechanism of apoptosis induction in primary CLL cells.
In silico analysis of methyltransferase domains involved in biosynthesis of secondary metabolites
Authors: Ansari Mohd Zeeshan , Sharma Jyoti , Gokhale Rajesh S , Mohanty Debasisa
Published: October 2008

Background

Secondary metabolites biosynthesized by polyketide synthase (PKS) and nonribosomal peptide synthetase (NRPS) family of enzymes constitute several classes of therapeutically important natural products like erythromycin, rapamycin, cyclosporine etc. In view of their relevance for natural product based drug discovery, identification of novel secondary metabolite natural products by genome mining has been an area of active research. A number of different tailoring enzymes catalyze a variety of chemical modifications to the polyketide or nonribosomal peptide backbone of these secondary metabolites to enhance their structural diversity. Therefore, development of powerful bioinformatics methods for identification of these tailoring enzymes and assignment of their substrate specificity is crucial for deciphering novel secondary metabolites by genome mining.

Results

In this work, we have carried out a comprehensive bioinformatics analysis of methyltransferase (MT) domains present in multi functional type I PKS and NRPS proteins encoded by PKS/NRPS gene clusters having known secondary metabolite products. Based on the results of this analysis, we have developed a novel knowledge based computational approach for detecting MT domains present in PKS and NRPS megasynthases, delineating their correct boundaries and classifying them as N-MT, C-MT and O-MT using profile HMMs. Analysis of proteins in nr database of NCBI using these class specific profiles has revealed several interesting examples, namely, C-MT domains in NRPS modules, N-MT domains with significant homology to C-MT proteins, and presence of NRPS/PKS MTs in association with other catalytic domains. Our analysis of the chemical structures of the secondary metabolites and their site of methylation suggested that a possible evolutionary basis for the presence of a novel class of N-MT domains with significant homology to C-MT proteins could be the close resemblance of the chemical structures of the acceptor substrates, as in the case of pyochelin and yersiniabactin. These two classes of MTs recognize similar acceptor substrates, but transfer methyl groups to N and C positions on these substrates.

Conclusion

We have developed a novel knowledge based computational approach for identifying MT domains present in type I PKS and NRPS multifunctional enzymes and predicting their site of methylation. Analysis of nr database using this approach has revealed presence of several novel MT domains. Our analysis has also given interesting insight into the evolutionary basis of the novel substrate specificities of these MT proteins.
The DrosophilaSTIM1 orthologue, dSTIM, has roles in cell fate specification and tissue patterning
Authors: Eid Jean-Pierre , Arias Alfonso Martinez , Robertson Hannah , Hime Gary R , Dziadek Marie
Published: October 2008

Background

Mammalian STIM1 and STIM2 and the single Drosophila homologue dSTIM have been identified as key regulators of store-operated Ca2+ entry in cells. STIM proteins function both as molecular sensors of Ca2+concentration in the endoplasmic reticulum (ER) and the molecular triggers that activate SOC channels in the plasma membrane. Ca2+ is a crucial intracellular messenger utilised in many cellular processes, and regulators of Ca2+ homeostasis in the ER and cytosol are likely to play important roles in developmental processes. STIM protein expression is altered in several tumour types but the role of these proteins in developmental signalling pathways has not been thoroughly examined.

Results

We have investigated the expression and developmental function of dSTIM in Drosophila and shown that dSTIM is widely expressed in embryonic and larval tissues. Using the UAS-Gal4 induction system, we have expressed full-length dSTIM protein and a dsRNAi construct in different tissues. We demonstrate an essential role for dSTIM in larval development and survival, and a tissue-specific role in specification of mechanosensory bristles in the notum and specification of wing vein thickness.

Conclusion

Our studies show that dSTIM regulates growth and patterning of imaginal discs and indicate potential interactions with the Notch and Wingless signaling pathways. These interactions may be relevant to studies implicating STIM family proteins in tumorigenesis.
The Helicobacter pylori duodenal ulcer promoting gene, dupAin China
Authors: Zhang Zhiyu , Zheng Qing , Chen Xiaoyu , Xiao Shudong , Liu Wenzhong , Lu Hong
Published: October 2008

Background

The prevalence of H. pylori is as high as 60–70% in Chinese population. Although duodenal ulcer and gastric cancer are both caused by H. pylori, they are at opposite ends of the spectrum and as such are considered mutually exclusive. Duodenal ulcer promoting (dupA) gene was reported to be associated with duodenal ulcer development. The aim of this study was to determine the prevalence of dupA gene of Helicobacter pylori in patients with various gastroduodenal diseases and to explore the association between the gene and other virulence factors.

Methods

H. pylori were isolated from gastric biopsies of patients with chronic gastritis, duodenal ulcer (DU), gastric ulcer (GU), or non-cardia gastric carcinoma. The dupA, cagA, vacA, iceA and babA2 genotypes were determined by polymerase chain reaction. Histological features of gastric mucosal biopsy specimens were graded based on the scoring system proposed by the updated Sydney system. IL-1β polymorphism was investigated using restriction fragment length polymorphism.

Results

Isolates from 360 patients including 133 with chronic gastritis, 101 with DU, 47 with GU, and 79 with non-cardia gastric carcinoma were examined. The dupA gene was detected in 35.3% (127/360) and the prevalence DU patients was significantly greater than that in gastric cancer or GU patients (45.5% vs. 24.1% and 23.4%, P < 0.05). Patients infected with dupA-positive strains had higher scores for chronic inflammation compared to those with dupA-negative strains (2.36 vs. 2.24, p = 0.058). The presence of dupA was not associated with the cagA, vacA, iceA and babA 2 genotypes or with IL-1β polymorphisms.

Conclusion

In China the prevalence of dupA gene was highest in DU and inversely related to GU and gastric cancer.
Respiratory syncytial virus glycoproteins uptake occurs through clathrin-mediated endocytosis in a human epithelial cell line
Authors: Gutiérrez-Ortega Abel , Sánchez-Hernández Carla , Gómez-García Beatriz
Published: October 2008

Cell-surface viral proteins most frequently enter the cell through clathrin or caveolae endocytosis. Respiratory syncytial virus antigen internalization by immune cells is via caveolin, however, uptake of paramyxovirus cell membrane proteins by non-immune cells is done through clathrin-coated pits. In this work, the uptake of respiratory syncytial virus cell surface glycoproteins by non-immune human epithelial cells was investigated through indirect immunofluorescence with polyclonal anti-RSV antibody and confocal lasser-scanner microscopy. Clathrin and caveolae internalization pathways were monitored through specific inhibitors monodansylcadaverine (MDC) and methyl-beta-cyclodextrin (MBCD), respectively. Internalization of RSV antigens was inhibited by MDC but not by MBCD, implying that clathrin-mediated endocytosis is the major uptake route of RSV antigens by an epithelial human cell line.
Significance of the entire C-terminus in biological activities mediated by the RON receptor tyrosine kinase and its oncogenic variant RON160
Authors: Lu Yi , Yao Hang-Ping , Wang Ming-Hai
Published: October 2008

The RON receptor tyrosine kinase regulates epithelial cell homeostasis and tumorigenesis by transducing multiple signals through its functional domains. The present study was to determine the significance of the entire C-terminus in RON or its variant RON160-mediated activities related to cell motility and tumorigenesis. Analysis of protein phosphorylation revealed that elimination of the entire C-terminus significantly impairs the ligand-dependent or independent RON or RON160 phosphorylation and dimerization. Phosphorylation of downstream signaling proteins such as Erk1/2, AKT, and p38 MAP kinase was also diminished in cells expressing the C-terminus-free RON or RON160. These dysfunctional activities were accompanied with the inability of truncated RON or RON160 to mediate cytoplasmic β-catenin accumulation. Functional analysis further demonstrated that truncation of the C-terminus significantly impairs RON or RON160-mediated cell proliferation, morphological changes, and cellular migration. Significantly, oncogenic RON160-mediated tumor growth in athymic nude mice was lost after the deletion of the C-terminus. Thus, the C-terminus is a critical component of the RON receptor. The entire C-terminus is required for RON or RON160-mediated intracellular signaling events leading to various cellular activities.
A quality assessment of genetic association studies supporting susceptibility and outcome in acute lung injury
Authors: Flores Carlos , del Mar Pino-Yanes Maria , Villar Jesús
Published: October 2008

Introduction

Clinical observations and animal models provide evidence that the development of acute lung injury (ALI), a phenomenon of acute diffuse lung inflammation in critically ill patients, is influenced by genetic factors. Association studies are the main tool for exploring common genetic variations underlying ALI susceptibility and/or outcome. We aimed to assess the quality of positive genetic association studies with ALI susceptibility and/or outcome in adults in order to highlight their consistency and major limitations.

Methods

We conducted a broad PubMed literature search from 1996 to June 2008 for original articles in English supporting a positive association (P ≤ 0.05) of genetic variants contributing to all-cause ALI susceptibility and/or outcome. Studies were evaluated based on current recommendations using a 10-point quality scoring system derived from 14 criteria, and the gene was considered as the unit of replication. Genes were also categorized according to biological processes using the Gene Ontology.

Results

Our search identified a total of 29 studies reporting positive findings for 16 genes involved mainly in the response to external stimulus and cell signal transduction. The genes encoding for interleukin-6, mannose-binding lectin, surfactant protein B, and angiotensin-converting enzyme were the most replicated across the studies. On average, the studies had an intermediate quality score (median of 4.62 and interquartile range of 3.33 to 6.15).

Conclusions

Although the quality of association studies seems to have improved over the years, more and better designed studies, including the replication of previous findings, with larger sample sizes extended to population groups other than those of European descent, are needed for identifying firm genetic modifiers of ALI.
Modelling of a housing estate with micro-combined heat and power for power flow studies
Authors: Sulka T , Jenkins N
Published: October 2008

A high concentration of micro-combined heat and power (mCHP) units leads to difficulties in predicting power flows in low-voltage electrical feeders. A simple model of a house with mCHP generation, which is combined with an estate model, is used to predict electrical network flows. The model of the estate includes representation of the residents’ behaviour and ambient weather conditions.

Results for an individual house, as well as electrical power flows for the estate feeder, are shown for three different seasons of a year.
Scenarios for examination of highly distributed power systems
Authors: Jardine C N , Ault G W
Published: October 2008

A set of three scenarios has been created in order to examine the incorporation of extensive penetrations of micro-generators into electricity networks (termed ‘highly distributed power systems’). The scenarios have been created as a synthesis of the Future Network Technologies scenarios and the UK domestic carbon model, and yields energy use and carbon dioxide emissions of the UK housing stock from inputs of household numbers, house type, thermal efficiency, appliance efficiency, as well as the number and efficiency of micro-generators used. The centralized supply mix also varies between scenarios and features extensive penetrations of large-scale renewables.

The scenarios illustrate the scale of change required to reduce CO2 emissions by 60 per cent by 2050, which has substantial impacts for electricity network operation. Moving from a centralized system to the one where one-third of electricity comes from distributed sources poses significant challenges including: reverse power flow on networks, load balancing, storage requirements, phase unbalance, harmonics, and ancillary services.
Economic dispatch of distributed combined heat and power systems participating in electricity spot markets
Authors: Ristic M , Brujic D , Thoma K
Published: October 2008

An optimization tool is proposed to determine the optimal operation schedule for distributed combined heat and power plants which participate in electricity spot markets. It was tested and analysed using realistic data for heat and electricity demands and their corresponding prices. The results show substantial cost savings compared with the benchmarked alternatives.
Developing and testing a generic micro-combined heat and power model for simulations of dwellings and highly distributed power systems
Authors: Kelly N J , Clarke J A , Ferguson A , Burt G
Published: October 2008

This paper elaborates an approach to the modelling of domestic micro-combined heat and power (μ-CHP) using a building simulation tool that can provide a detailed picture of the environmental performance of both the μ-CHP heating system and the dwelling it serves. The approach can also provide useful data for the modelling of highly distributed power systems (HDPS).

At the commencement of the work described in this paper no μ-CHP device model that was compatible with a building simulation tool was available. The development of such a model is described along with its calibration and verification.

The simulation tool with the device model was then applied to the analysis of a dwelling with a Stirling engine-based heating system. Different levels of thermal insulation and occupancy types were modelled. The energy and environmental performance of the μ-CHP device was quantified for each case; additionally, the potential for its participation in the control and operation of an HDPS was assessed.

Analysis of the simulation results indicated that the parasitic losses associated with the μ-CHP system balance of plant reduced the overall heating system efficiency by up to 40 per cent. Performance deteriorated with increasing levels of insulation in the dwelling, resulting in reduced thermal efficiency and increased cycling, though overall fuel use was reduced. The analysis also indicated that the device was generally available to participate in HDPS control for greater than 90 per cent of the simulation time. The potential length of the participation time ranged from 1 to 800+min and depended upon the state of the μ-CHP system thermal buffer and prevailing heat loads. Probabilities for different participation times and modes were calculated.
Assessment of highly distributed power systems using an integrated simulation approach
Authors: Burt G M , Elders I M , Galloway S J , Kelly N J , Tumilty R M
Published: October 2008

In a highly distributed power system (HDPS), micro renewable and low carbon technologies would make a significant contribution to the electricity supply. Further, controllable devices such as micro combined heat and power (CHP) could be used to assist in maintaining stability in addition to simply providing heat and power to dwellings. To analyse the behaviour of such a system requires the modelling of both the electrical distribution system and the coupled microgeneration devices in a realistic context.

In this paper a pragmatic approach to HDPS modelling is presented: microgeneration devices are simulated using a building simulation tool to generate time-varying power output profiles, which are then replicated and processed statistically so that they can be used as boundary conditions for a load flow simulation; this is used to explore security issues such as under and over voltage, branch thermal overloading, and reverse power flow.

Simulations of a section of real network are presented, featuring different penetrations of micro-renewables and micro-CHP within the ranges that are believed to be realistically possible by 2050. This analysis indicates that well-designed suburban networks are likely to be able to accommodate such levels of domestic-scale generation without problems emerging such as overloads or degradation to the quality of supply.
Energy analysis and environmental life cycle assessment of a micro-wind turbine
Authors: Allen S R , Hammond G P , McManus M C
Published: October 2008

The life cycle energy use and environmental impact of an installed micro-wind turbine for domestic (residential) electricity generation has been determined. The turbine examined was a horizontal-axis wind turbine, which has a rotor diameter of 1.7 m, a power rating of 600 W at 12 m/s, and an assumed lifetime of 15 years. The system boundaries for the study encompass energy and material resources in the ground and extend to the point of delivery of electricity. The energy output of the turbine in different terrains has been estimated via a dataset of hourly measured wind speeds, and the environmental impact of producing and maintaining the micro-wind turbine was determined. The environmental performance of the turbine was assessed by assuming that each unit of electricity generated displaces (avoids the use of) a unit of grid electricity. The whole life cycle performance of a micro-wind turbine was found to be dependant on a number of factors, primarily the geographical positioning of the turbine, the available wind resource, and the use of recycled materials within the production of the microturbine.
Risk assessment of UK electricity supply in a rapidly evolving energy sector
Authors: Hammond G P , Waldron R
Published: October 2008

A range of major risks associated with a rapidly changing United Kingdom (UK) electricity sector have been identified and quantified with the aid of various stakeholder groups (academic researchers, civil servants, electricity companies, ‘green’ groups, power system engineers, and various others), who completed an online internet questionnaire. Each stakeholder ranked potential risks according to the perceived ‘severity of impact’ and ‘likelihood of occurrence’ using a three-point scale. The data were then used to perform a ranking of the risks by multiplying scores for impact and occurrence. There was some variation between the different stakeholder groups, but similar risks were ranked highly by each group. The main risks were identified as being energy security issues (the highest score), lack of investment in new infrastructure, the closure of old coal and nuclear plants leading to reduced network capacity, severe weather events, and inadequate spare capacity margins generally. The trial illustrates the potential of using risk assessment techniques to evaluate developing risks to the UK power landscape. Clearly such an exercise would need to be carried out periodically if it were to maintain its value to the industry, its stakeholders, and to policy makers.
Microgrids and virtual power plants: Concepts to support the integration of distributed energy resources
Authors: Pudjianto D , Ramsay C , Strbac G
Published: October 2008

This article presents the concepts of the microgrid and the virtual power plant (VPP) as vehicles to facilitate cost-efficient integration of distributed energy resources (DERs) into the existing power system. These concepts were designed to enhance the system value and the controllability of DER and to provide frameworks for the development of interfaces among energy and ancillary service resources, system operators, and energy market participants. Through aggregation, DER access to energy markets is facilitated, and DER-based system support and ancillary services can be provided. By enabling this additional functionality, it is envisaged that system performance measured in the form of energy efficiency, power quality, security, and economic operation can be improved. In this paper, the technical and commercial functionality facilitated through the microgrid and VPP concepts is described. The paper concludes with case studies demonstrating the application of the concepts on a test system.
Modelling the impact of micro-combined heat and power generators on electricity distribution networks
Authors: Thomson M , Infield D
Published: October 2008

This paper investigates potential technical effects that a high take up of domestic micro-CHP could have on an electricity distribution system. This study is based on a combination of house-by-house energy use modelling and network power-flow analysis. A variety of micro-CHP technologies are represented, including Stirling engines, internal combustion engines, and fuel cells. These have different heat-to-power ratios and thus different impacts on the electricity system. The results and discussion focus on voltage rise, which is considered to be the primary constraint on allowable penetration.
Fuel cells as distributed generation
Authors: Cruden A , Houghton T , Gair S , Duerr M , Agnew G D , Stewart E M , Lutz A
Published: October 2008

This paper presents an overview of fuel cells as a form of distributed generation within the context of a highly distributed power system, by discussing some example demonstration systems categorized by the type of primary fuel used, namely fossil fuels, hydrogen gas, or biofuels. It discusses the background to fuel cells as a stationary, grid connected, power source, briefly compared with conventional thermal electrical generation, while describing the main characteristics of their performance and an electric equivalent circuit model. Additionally, it presents a view of the current state of commercialization of fuel cell technology for stationary power applications.
Samuel Wilks (1824–1911): neurologist and generalist of the Mid-Victorian Era
Authors: Eadie Mervyn J
Published: October 2008

Sir Samuel Wilks, sometime Physician to Guy's Hospital and President of the Royal College of Physicians (1896–99), was regarded as the leading British scientific physician of his day. His contributions to gastroenterology, cardiology and clinical science in general have been emphasized in recent times. He also recognized that syphilis affected the internal organs as well as the skin. In 1866 he realised that epileptogenesis occurred in the cerebral cortex: independently of Sir Charles Locock (1799–1875), he discovered the antiepileptic properties of potassium bromide. He provided possibly the first account of alcoholic peripheral neuritis and published an early account of probable myasthenia gravis.
Jean Langlais (1907–91): an historical case of a blind organist with stroke-induced aphasia and Braille alexia but without amusia
Authors: Fisher C A H , Larner A J
Published: October 2008

The subject of a prior report of a blind organist with aphasia and Braille alexia without amusia, published in French, has been identified as Jean Langlais. His artistic and medical history is presented, the latter via translation of the original 1987 paper.
Maud Forrester-Brown (1885–1970): Britain's first woman orthopaedic surgeon
Authors: Kirkup John
Published: October 2008

In an era when few women achieved consultant surgical status, Miss Forrester-Brown proved not only a pioneer orthopaedic surgeon but also demonstrated that her sex was no bar to this physically demanding specialty. Virtually on her own she consolidated a series of clinics throughout three counties, elevating the Bath and Wessex Orthopaedic Hospital to national prominence. In addition to her books and journal communications, she maintained strong links with distinguished orthopaedic surgeons in Europe and America to keep abreast of innovations beneficial to her patients. Yet her shoulder was not always at the wheel, for she enjoyed horse-riding, ski-ing and swimming, and she was deeply interested in literature and art.
Louisa Garrett Anderson (1873–1943), surgeon and suffragette
Authors: Geddes Jennian F
Published: October 2008

Louisa Garrett Anderson, daughter of Britain's first woman doctor, has been largely forgotten today despite the fact that her contribution to the women's movement was as great as that of her mother. Recognized by her contemporaries as an important figure in the suffrage campaign, Anderson chose to lend her support through high-profile action, being one of the few women doctors in her generation who risked their professional as well as their personal reputation in the fight for women's rights by becoming a suffragette – in her case, even going so far as to spend a month in prison for breaking a window on a demonstration. On the outbreak of war, with only the clinical experience she had gained as outpatient surgeon in a women's hospital, Anderson established a series of women-run military hospitals where she was a Chief Surgeon. The most successful was the Endell Street Military Hospital in London, funded by the Royal Army Medical Corps and the only army hospital ever to be run and staffed entirely by women. Believing that a doctor had an obligation to take a lead in public affairs, Anderson continued campaigning for women's issues in the unlikely setting of Endell Street, ensuring that their activities remained in the public eye through constant press coverage. Anderson's achievement was that her work played no small part in expunging the stigma of the militant years in the eyes of the public and – more importantly – was largely instrumental in putting women doctors on equal terms with their male colleagues.
The life and work of Abu ul-Ala Shirazi (d. 1001): a Persian pioneer in the treatment of malaria, in the style of Rhazes (865–925)
Authors: Mahmoudian Masoud , Rahimi-Moghaddam Parvaneh
Published: October 2008

Abu ul-Ala Shirazi, who lived around the 10th century at the Court of Amir Azud ul-Duleh Bueieh (902–951) from the Dailami Dynasty, found that arsenic, known as sam-al-far, could cure malaria. A clinical trial dating from the 10th century demonstrates Abu ul-Ala's intelligence and careful clinical observation, in the tradition of Rhazes' practice based on experimentation and clinical trial.
The Shorts of Bury St Edmunds: Medicine, Catholicism and politics in the 17th century
Authors: Young Francis
Published: October 2008

The Short family of Bury St Edmunds produced at least eight doctors between the first half of the 17th century and the first half of the 18th. Some of these practised locally and others went on to achieve fame in London or abroad. They included Richard Short (d. 1668), a medical polemicist, and Thomas Short (1635–85) who treated Charles II in his last illness and became the subject of poetry and other literature. The Shorts generated controversy through their adherence to the Roman Catholic faith at a time of persecution and suspicion. Richard Short used medical polemic as a vehicle for advancing his religious views, and his son and nephew became involved in James II's political programme to introduce religious toleration in 1688. After the Revolution the Shorts withdrew from political life but continued in their medical practice and their recusancy. This paper is the first to unravel the family relationships of the Shorts, which previously have eluded most historians.
Sir Michael Foster MD FRS (1836–1907): the rise of the British school of physiology
Authors: Hawgood Barbara J
Published: October 2008

In 1867 William Sharpey (1802–80), Professor of General Anatomy and Physiology at University College, London, appointed Michael Foster to the unique post of Teacher of Practical Physiology; in Britain the study of experimental physiology was dormant. In 1870 Foster accepted a Praelectorship in Physiology at Trinity College, Cambridge, and soon established a school of physiology. He was the first Cambridge Professor of Physiology (1883–1903). Foster, a great teacher, had a remarkable ability to attract talented students and to inspire them to undertake research. He himself took inspiration from the scientific philosophy of Thomas Henry Huxley (1825–95) and of Claude Bernard (1813–78). Foster was active in the foundation of the Physiological Society (1876), and founded and edited the Journal of Physiology (1878). He was interested in the scientific training of medical students and wrote a highly lauded Text Book of Physiology (1877). Physiology became a profession in its own right and British physiologists were in the vanguard of research.
William Allen Miller (1817–70): a distinguished scientist re-discovered
Authors: Ashley-Miller Michael
Published: October 2008

Dr William Allen Miller developed an early interest in science and astronomy at secondary school. Although qualifying in medicine, he pursued a career in Chemistry at King's College, London. A particular interest in spectrum analysis led to a collaboration with Dr Huggins in examining the spectra of stars. For this work they each received the Gold Medal of the Royal Astronomical Society. His subsequent work at King's College, the Royal Society, the Courts of Law and for various Government enterprises earned him an outstanding scientific and advisory reputation.
Thermodynamic examination of trinucleotide bulged RNA in the context of HIV-1 TAR RNA
Authors: Carter-O'Connell Ian , Booth David , Eason Bryan , Grover Neena
Published: October 2008

RNA structures contain many bulges and loops that are expected to be sites for inter- and intra-molecular interactions. Nucleotides in the bulge are expected to influence the structure and recognition of RNA. The same stability is assigned to all trinucleotide bulged RNA in the current secondary structure prediction models. In this study thermal denaturation experiments were performed on four trinucleotide bulged RNA, in the context of HIV-1 TAR RNA, to determine whether the bulge sequence affects RNA stability and its divalent ion interactions. Cytosine-rich bulged RNA were more stable than uracil-rich bulged RNA in 1 M KCl. Interactions of divalent ions were more favorable with uracil-rich bulged RNA by ∼2 kcal/mol over cytosine-rich bulged RNA. The UCU-TAR RNA (wild type) is stabilized by 1.7 kcal/mol in 9.5 mM Ca2+ as compared with 1 M KCl, whereas no additional gain in stability is measured for CCC-TAR RNA. These results have implications for base substitution experiments traditionally employed to identify metal ion binding sites. To our knowledge, this is the first systematic study to quantify the effect of small sequence changes on RNA stability upon interactions with divalent ions.
Evolution of Arabidopsis thaliana microRNAs from random sequences
Authors: Fenselau de Felippes Felipe , Schneeberger Korbinian , Dezulian Tobias , Huson Daniel H. , Weigel Detlef
Published: October 2008

One mechanism for the origin of new plant microRNAs (miRNAs) is from inverted duplications of transcribed genes. However, even though many young MIRNA genes have recently been identified in Arabidopsis thaliana, only a subset shows evidence for having evolved by this route. We propose that the hundreds of thousands of partially self-complementary foldback sequences found in a typical plant genome provide an alternative path for miRNA evolution. Our genome-wide analyses of young MIRNA genes suggest that some arose from DNA that either has self-complementarity by chance or that represents a highly eroded inverted duplication. These observations are compatible with the idea that, following capture of transcriptional regulatory sequences, random foldbacks can occasionally spawn new miRNAs. Subsequent stabilization through coevolution with initially fortuitous targets may lead to fixation of a small subset of these proto-miRNA genes.