bluuebunny/crossref_metadata_2025 huggingface dataset:
The impact of monitoring Epstein–Barr virus PCR in paediatric bone marrow transplant patients: Can it successfully predict outcome and guide intervention?
Authors: Greenfield Hayley M. , Gharib Maged I. , Turner Andrew J.L. , Guiver Malcolm , Carr Trevor , Will Andrew M. , Wynn Robert F.
Published: October 2005

Background

Epstein–Barr virus (EBV) associated lymphoproliferative disease is a complication of haemopoietic stem cell transplantation (HSCT). In certain groups (unrelated and mismatched donor transplants, T‐cell depleted) the risk may be as high as 25% with significant morbidity and mortality. Strategies to predict the impending development of this disorder and allow early intervention have therefore assumed importance. We routinely screen the peripheral blood of all recipients of allogeneic HSCT to detect EBV DNA by quantitative polymerase chain reaction (PCR) technology and report here how this correlates with clinical disease and management.

Procedure

Data on 28 successive patients who underwent HSCT at our institution were reviewed. The relationship between EBV reactivation demonstrated by quantitative PCR and development of post transplant lymphoproliferative disease (PTLD) was determined.

Results

EBV reactivation occurred in 68% of patients, however only 7% developed clinical PTLD. Patients with high level reactivation (n = 9) had more frequent episodes of reactivation and all patients who progressed to overt PTLD were found in this group. In contrast none of those patients with low level reactivation (n = 10) or persistently negative results (n = 9) showed any signs of clinical disease. Anti‐CD20 monoclonal antibody (Rituximab) therapy was instigated in both cases of proven PTLD and three cases of high level reactivation with successful outcomes. Response to treatment was associated with a prompt decline in viral copy number.

Conclusions

Our results indicate that EBV reactivation is a common occurrence in the paediatric allogeneic transplant setting and that only a proportion of patients will progress to PTLD. Frequent monitoring may help to predict those at highest risk and guide intervention. Pediatr Blood Cancer © 2005 Wiley‐Liss, Inc.
How well does the Canadian haemophilia Outcomes‐Kids' Life Assessment Tool (CHO‐KLAT) measure the quality of life of boys with haemophilia?
Authors: Young Nancy L. , Bradley Catharine S. , Wakefield Cindy D. , Barnard Dorothy , Blanchette Victor S. , McCusker Patricia J.
Published: October 2005

Background

It is important to measure the quality of life (QoL) of boys with haemophilia, because the diagnosis has a significant impact on their lives and this impact fluctuates over time. A disease‐specific measure of QoL is required because the aspects of life that are affected by haemophilia may differ from those assessed by generic QoL measures. This paper describes the final phase of development of a disease‐specific measure of QoL for boys with haemophilia: the Canadian Haemophilia Outcomes‐Kids Life Assessment Tool (CHO‐KLAT).

Procedure

A 79‐item version of the CHO‐KLAT was administered to 52 children. A detailed item analysis was conducted to shorten the CHO‐KLAT. The reliability of the revised version was assessed using intraclass correlation coefficients. Validity was assessed by comparing it to the PedsQL and the HaemoQoL.

Results

The item analysis resulted in the retention of 35 strongly performing items (CHO‐KLAT35). These items were aggregated into the CHO‐KLAT35 summary score. Repeated measures reliability of the CHO‐KLAT35 was 0.74 for children and 0.83 for parents, and the child–parent concordance was 0.75. The validity of the CHO‐KLAT35 was confirmed by a correlation of 0.78 with the Haemo‐QoL and of 0.59 with the PedsQL.

Conclusions

The CHO‐KLAT35 is a reliable and valid measure of QoL for boys with haemophilia. Pediatr Blood Cancer 2006;47:305–311. © 2005 Wiley‐Liss, Inc.
Gefitinib is effective against juvenile pilocytic astrocytoma in vitro
Authors: Foreman Nicholas K. , Gore Lia , Wells Daniel , Straessle Jennifer , Heideman Richard , Donson Andrew M.
Published: October 2005

Background

Juvenile pilocytic astrocytomas (JPAs) are the most common central nervous system tumors in children. If completely resected, JPAs are associated with an excellent outcome. However, there is need for additional therapeutic approaches for those JPAs which are incompletely resected and fail subsequent standard chemotherapy/radiation. To explore the possibility for a novel therapeutic approach we measured the effect of the epidermal growth factor receptor (EGFR) small molecule tyrosine kinase inhibitor gefitinib on five JPA primary cell‐cultures.

Procedure

Due to a lack of established cell‐lines of JPA very few in vitro drug sensitivity assays have been performed. In this study we have succeeded in propagating short‐term primary cell‐cultures established from surgical specimens. The effect of gefitinib on proliferation in JPA derived primary cell‐cultures was measured by a standard tritiated thymidine incorporation assay. The level of expression of EGFR, the intended target of gefitinib, was measured by immunohistochemistry, flow cytometry and RT‐PCR.

Results

Gefitinib was shown to inhibit proliferation in all five JPA cell‐cultures tested, with IC‐50's between 1.6 and 9.6 µM. However, EGFR protein and mRNA expression was undetectable. Further studies with cetuximab, an EGFR‐specific inhibitory monoclonal antibody, showed no effect on proliferation in JPA.

Conclusions

Based on these preclinical data, gefitinib may be a suitable salvage chemotherapy drug to explore further in those patients with JPA who have recurred after primary chemotherapy. Of interest, it appears that the anti‐tumor effect of gefitinib in JPA cell‐cultures may be mediated through a pathway other than EGFR inhibition. Pediatr Blood Cancer 2006;47:293–298. © 2005 Wiley‐Liss, Inc.
Treatment of infantile choriocarcinoma of the liver
Authors: Yoon Janet M. , Burns R. Cartland , Malogolowkin Marcio H. , Mascarenhas Leo
Published: October 2005

Primary choriocarcinoma of the liver is an extremely rare childhood malignancy frequently associated with clinical instability at initial presentation. It often mimics other benign and malignant childhood liver tumors. Prompt diagnosis and initiation of treatment are necessary to attain a successful outcome. We describe a critically ill infant with metastatic choriocarcinoma whose diagnosis was based on radiographic and tumor marker findings, without an initial biopsy, and her successful management with neo‐adjuvant chemotherapy and delayed surgery. She is currently in continuous remission 24 months from diagnosis. Pediatr Blood Cancer 2007;49:99–102. © 2005 Wiley‐Liss, Inc.
Ovarian germ cell tumors in children: A clinical study of 66 patients
Authors: De Backer Antoine , Madern Gerard C. , Oosterhuis J. Wolter , Hakvoort‐Cammel Friederike G.A.J. , Hazebroek Frans W.J.
Published: October 2005

Background

Ovarian germ cell tumors are rare in childhood. The aim of this study is to review clinical presentation, management, and outcome in a two‐center series of girls with ovarian germ cell tumor.

Procedure

The records of 66 patients (median age 9 years) with histologically proven ovarian germ cell tumor (either benign or malignant), treated over a 44‐year‐span, were reviewed.

Results

Pain and an abdominal mass were the most frequent symptoms. The tumors were right‐sided in 35, left‐sided in 28, and bilateral in 3. Most patients (52) were stage I, 4 were stage II, 6 stage III, and 1, with liver metastases, stage IV. Sixteen patients had an emergency operation for tumor torsion. Unilateral salpingo‐oophorectomy was the most frequently performed procedure (n = 46), and ovarian‐sparing tumorectomy was performed in 9 patients (one bilaterally). Histologically, teratomas were found most frequently (mature: 45, immature: 9), followed by mixed tumors (n = 7), yolk sac tumors (n = 3), dysgerminoma (n = 2), gonadoblastoma (n = 2), and embryonal carcinoma (n = 1). Surgical removal of the tumor with or without the ovary and/or adnex was the sole treatment in 55 patients, chemotherapy was administered in 10 and radiotherapy + chemotherapy in one. Intra‐operative spillage of tumoral fluid occurred in six; this did not influence outcome in five. Recurrence was observed in three patients. Two patients, with malignant disease, died. The 64 survivors are now between 8 months and 44 years after treatment.

Conclusions

With a recurrence rate of 4.5% and a mortality rate of 3%, this series confirms the excellent prognosis for girls with ovarian germ cell tumor (GCT). Pediatr Blood Cancer 2006, 46:459–464. © 2005 Wiley‐Liss, Inc.
Vinylic and ring‐opening metathesis polymerization of norbornene with bis(β‐ketoamine) cobalt complexes
Authors: Bao Feng , Lü Xing‐Qiang , Gao Haiyang , Gui Guoqiu , Wu Qing
Published: October 2005

Cobalt complexes 1–4 bearing N,O‐chelate ligands based on condensation products of 1‐phenyl‐3‐methyl‐4‐benzoyl‐5‐pyrazolone with aniline, o‐methylaniline, α‐naphthylamine, and p‐nitroaniline, respectively, were synthesized, and the structures of 1 and 4 were characterized by single‐crystal X‐ray diffraction analyses. The bis(β‐ketoamine) cobalt complexes could act as moderately active catalyst precursors for norbornene polymerization with the activation of methylaluminoxane. This catalytic reaction proceeded mainly through a vinyl‐type polymerization mechanism. 1H NMR and IR showed that in all cases, a small amount of double bonds raised from ring‐opening metathesis polymerization (ROMP) was present in the polymerization products. The variation of the polymerization conditions affected the ROMP unit ratio in the polynorbornenes. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 5535–5544, 2005
Structural/compositional nanoheterogeneity and glass‐transition plurality in amorphous polycyanurate–poly(tetramethylene glycol) hybrid networks
Authors: Bershtein V. A. , David L. , Egorov V. M. , Fainleib A. M. , Grigorieva O. , Bey I. , Yakushev P. N.
Published: October 2005

The nanostructure and dynamics over the temperature range of −140 to 300 °C were studied in a series of polycyanurate (PCN)–poly(tetramethylene glycol) (PTMG) hybrid networks by wide‐angle X‐ray diffraction and small‐angle X‐ray scattering, with a synchrotron radiation setup, and by differential scanning calorimetry (DSC) and laser‐interferometric creep rate spectroscopy (CRS) techniques, respectively. The networks were synthesized from the dicyanate ester of bisphenol A and hydroxyl‐terminated PTMG with a number‐average molecular weight of 1.000 g/mol; the PTMG content varied from 0 to 40 wt %, and the degree of its chemical incorporation into the PCN network changed from 78.8 to 97%. The noncrystalline structure and considerable structural nanoheterogeneity of the hybrid networks were shown. CRS/DSC analysis revealed a complicated dynamic behavior, that is, a wide dispersion of glass transitions in the hybrid networks due to the presence of nanodomains with different degrees of rigid crosslinking (i.e., compositional nanoheterogeneity). Besides the physical significance, the plurality of glass transitions found in the PCN–PTMG hybrid networks was also of practical interest because it resulted in increasing mechanical strength of the brittle PCN network due to microplasticity arising at room temperature and moderate temperatures and the retention of some rigidity and creep resistance at temperatures much higher than the basic glass‐transition temperature. © 2005 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 43: 3261–3272, 2005
Use of symbolic algebra in the calculation of hyperspherical harmonics
Authors: Wang Desheng , Kuppermann Aron
Published: October 2005

A symbolic algebra method for determining democratic hyperspherical harmonics (HH) for three‐particle and four‐particle systems is given. It is based on a recursion relation that, starting from a complete set of such harmonics for a given value n of the system's grand‐canonical angular momentum quantum number, determines a similarly complete set for n + 1. Using this method, all 2.3 million HH for n up to 40 for the three‐particle case and all 43.8 million for n up to 30 for the four particle case were determined. The method, details, and results of its implementation are described. © 2005 Wiley Periodicals, Inc. Int J Quantum Chem, 2006
Complexes self‐associate by hydrogen bonding and metallophilic attraction: Theoretical study
Authors: Mendizabal Fernando , Reyes Dana , Olea‐Azar Claudio
Published: October 2005

Hydrogen bonding and metallophilic attractions are studied in the model systems: [(AuNH3Cl)2], [(AuNH(CH3)2Cl)2], [{Au2(μ‐SH)(PH2O)(PH2OH)}2], [(CuNH3Cl)2], and [{Cu(NH3)Cl}4] at the Hartree–Fock (HF) and second‐order Møller–Plesset (MP2) levels. The two interactions are found to be comparable and prevailing in the final structure. It is determined that the aurophilic contact has a same magnitude that the hydrogen bonding, and is stronger than the cuprophilic interaction. The presence of hydrogen bond directs the growth of the crystal. © 2005 Wiley Periodicals, Inc. Int J Quantum Chem, 2006
Tetraalkylammonium halides as chemical standards for positive electrospray ionization with ion mobility spectrometry/mass spectrometry
Authors: Viidanoja Jyrki , Sysoev Alexey , Adamov Alexey , Kotiaho Tapio
Published: October 2005

Chemical standards for positive ion mode electrospray ionization ion mobility spectrometry/mass spectrometry (ESI(+)‐IMS/MS) are suggested. The low clustering tendency of tetraalkylammonium halides makes them ideal chemical standards for ESI(+)‐IMS/MS. A homologous series of these compounds forms a useful external standard for instrument testing and resolution calibration of an IMS instrument. Selected homologues or a mixture of tetraalkylammonium halides can be used as mobility standards in the analytical runs. Absolute and relative reduced mobilities were calculated for C2C8, C10 and C12 tetraalkylammonium halides. Absolute reduced mobilities in nitrogen were 1.88, 1.56, 1.33, 1.15, 1.02, 0.92, 0.84, 0.73, and 0.67 cm2 V−1 s−1, for C2C8, C10 and C12 tetraalkylammonium halides, respectively. Relative reduced mobilities (relative to 2,6‐di‐tert‐butylpyridine) for the same compounds were 1.20, 1.00, 0.855, 0.743, 0.658, 0.59, 0.54, 0.47, and 0.43, respectively. Copyright © 2005 John Wiley & Sons, Ltd.
Simultaneous determination of carisoprodol and meprobamate in human hair using solid‐phase extraction and gas chromatography/mass spectrometry of the trimethylsilyl derivatives
Authors: Kim Jin Young , In Moon Kyo , Paeng Ki‐Jung , Chung Bong Chul
Published: October 2005

Carisoprodol (CSP) is a musculoskeletal relaxant whose active metabolite is meprobamate (MPB). This drug has recently been noticed to be abused as an inexpensive alternative to illicit drugs in Korea. A method using solid‐phase extraction (SPE) and gas chromatography/mass spectrometry (GC/MS) was developed for the determination of CSP and MPB in human hair. Hair samples (30 mg) were washed with distilled water and acetone, cut into small fragments (<1 mm), incubated in 1.0 M HCl overnight at 50°C, and then adjusted to pH 6.5. The drugs were extracted from the resulting hydrolyzed solutions using a SPE column. The eluents were evaporated to dryness, then derivatized using N,O‐bis(trimethylsilyl)trifluoroacetamide (BSTFA) with 1% trimethylchlorosilane (TMCS) at 120°C for 30 min. The derivatized extract (1 µL) was injected into the GC/MS system. Recoveries were in the range of 91.5–93.1% for CSP and 85.5–93.0% for MPB. The linear ranges were 0.5–10.0 ng/mg for both CSP and MPB with good correlation coefficients (r2 = 0.995). The intra‐day precision and accuracy ranged from 1.5 to 9.3% and −17.5 to 3.6%, respectively, and the inter‐day precision and accuracy ranged from 3.9 to 6.2% and −15.0 to −3.9%, respectively. The limits of detection for CSP and MPB were 0.13 and 0.12 ng/mg, respectively. The applicability of the method was proven by analyzing a hair sample from an authentic abuser. Copyright © 2005 John Wiley & Sons, Ltd.
Binding characteristics of the 5‐HT2A receptor antagonists altanserin and MDL 100907
Authors: Kristiansen Heidi , Elfving Betina , Plenge Per , Pinborg Lars H. , Gillings Nic , Knudsen Gitte M.
Published: October 2005

To study the 5‐HT2A receptors in the living human brain, using positron emission tomography (PET), two selective radiotracers are currently in use: [18F]altanserin and [11C]MDL 100907. It is, however, currently unknown to what extent data obtained with either tracer are directly comparable. The aim of this study was to compare binding characteristics of these two radiotracers in rat brain with respect to affinity (Kd), receptor binding density (Bmax), binding potential (BP), and nonspecific binding. Further, binding kinetics, sensitivity towards competition with the endogenous transmitter serotonin, and the competitive/noncompetitive interaction between the two radioligands were evaluated. In addition, the selectivity of [18F]altanserin for the 5‐HT2A receptor was assessed.

The Kd value of [18F]altanserin and [3H]MDL 100907 was in the order of 0.3 nM. Bmax in frontal cortex was 523 and 527 fmol/mg protein, respectively. The binding of [18F]altanserin was not influenced by blocking either the 5‐HT2B/2C or the α1‐adrenergic receptors. At 37°C the association t1/2 was 2.8 and 2.7 min and the dissociation t1/2 was 11 and 13.5 min for [18F]altanserin and [3H]MDL 100907, respectively.

Both radioligands were displaced by 5‐HT, only at high concentrations; the Ki value of 5‐HT ranging between 650 and 3,300 nM. This indicates that binding of both radioligands in PET studies is not directly influenced by changes in endogenous 5‐HT.

Overall, the binding of [18F]altanserin and [3H]MDL 100907 to the 5‐HT2A receptor was very comparable, showing selective high affinity binding in the subnanomolar range. Synapse 58:249–257, 2005. © 2005 Wiley‐Liss, Inc.
An animal model of chronic inflammatory pain: Pharmacological and temporal differentiation from acute models
Authors: Wilson Alex W. , Medhurst Stephen J. , Dixon Claire I. , Bontoft Nick C. , Winyard Lisa A. , Brackenborough Kim T. , De Alba Jorge , Clarke Christopher J. , Gunthorpe Martin J. , Hicks Gareth A. , Bountra Chas , McQueen Daniel S. , Chessell Iain P.
Published: October 2005

Clinically, inflammatory pain is far more persistent than that typically modelled pre‐clinically, with the majority of animal models focussing on short‐term effects of the inflammatory pain response. The large attrition rate of compounds in the clinic which show pre‐clinical efficacy suggests the need for novel models of, or approaches to, chronic inflammatory pain if novel mechanisms are to make it to the market. A model in which a more chronic inflammatory hypersensitivity phenotype is profiled may allow for a more clinically predictive tool. The aims of these studies were to characterise and validate a chronic model of inflammatory pain. We have shown that injection of a large volume of adjuvant to the intra‐articular space of the rat knee results in a prolonged inflammatory pain response, compared to the response in an acute adjuvant model. Additionally, this model also results in a hypersensitive state in the presence and absence of inflammation. A range of clinically effective analgesics demonstrate activity in this chronic model, including morphine (3 mg/kg, t.i.d.), dexamethasone (1 mg/kg, b.i.d.), ibuprofen (30 mg/kg, t.i.d.), etoricoxib (5 mg/kg, b.i.d.) and rofecoxib (0.3–10 mg/kg, b.i.d.). A further aim was to exemplify the utility of this chronic model over the more acute intra‐plantar adjuvant model using two novel therapeutic approaches; NR2B selective NMDA receptor antagonism and iNOS inhibition. Our data shows that different effects were observed with these therapies when comparing the acute model with the model of chronic inflammatory joint pain. These data suggest that the chronic model may be more relevant to identifying mechanisms for the treatment of chronic inflammatory pain states in the clinic.
Inhibition of neuronal nitric‐oxide synthase by phosphorylation at Threonine1296 in NG108‐15 neuronal cells
Authors: Song Tao , Hatano Naoya , Kume Kodai , Sugimoto Katsuyoshi , Yamaguchi Fuminori , Tokuda Masaaki , Watanabe Yasuo
Published: October 2005

We demonstrate that neuronal nitric‐oxide synthase (nNOS) is directly inhibited through the phosphorylation of Thr1296 in NG108‐15 neuronal cells. Treatment of NG108‐15 cells expressing nNOS with calyculin A, an inhibitor of protein phosphatase 1 and 2A, revealed a dose‐dependent inhibition of nNOS enzyme activity with concomitant phosphorylation of Thr1296 residue. Cells expressing a phosphorylation‐deficient mutant in which Thr1296 was changed to Ala proved resistant to phosphorylation and suppression of NOS activity. Mimicking phosphorylation mutant of nNOS in which Thr1296 is changed to Asp showed a significant decrease in nNOS enzyme activity, being competitive with NADPH, relative to the wild‐type enzyme. These data suggest that phosphorylation of nNOS at Thr1296 may involve the attenuation of nitric oxide production in neuronal cells through the decrease of NADPH‐binding to the enzyme.
A Holocene Pollen and Diatom Record from Vanderlin Island, Gulf of Carpentaria, Lowland Tropical Australia
Authors: Prebble Matiu , Sim Robin , Finn Jan , Fink David
Published: October 2005

Sedimentary, palynological and diatom data from a dunefield lake deposit in the interior of Vanderlin Island in the Gulf of Carpentaria are presented. Prior to the formation of present perennial lake conditions, the intensified Australian monsoon associated with the early Holocene marine transgression allowed Cyperaceae sedges to colonise the alluvial margins of an expansive salt flat surrounded by an open Eucalyptus woodland. As sea level stabilised between 7500 and 4500 cal yr B.P. coastal dunes ceased to develop allowing dense Melaleuca forest to establish in a Restionaceae swamp. Dune-sand input into the swamp was diminished further as the increasingly dense vegetation prevented fluvial and aeolian transported sand arriving from coastal sources. This same process impounded the drainage basin allowing a perennial lake to form between 5500 and 4000 cal yr B.P. Myriophyllum and other aquatic taxa colonised the lake periphery under the most extensive woodland recorded for the Holocene. The palynological data support an effective precipitation model proposed for northern Australia that suggests more variable conditions in the late Holocene. A more precise measure of effective precipitation change is provided by diatom-based inferences that indicate few changes in lake hydrology. Such interpretations are explained in terms of palynological sensitivity to adjustments in local fire regimes where regional precipitation change may only be recorded indirectly through fire promoting mechanisms, including intensified ENSO periodicity and human impact.
Application of multirate flowing fluid electric conductivity logging method to well DH‐2, Tono Site, Japan
Authors: Doughty Christine , Takeuchi Shinji , Amano Kenji , Shimo Michito , Tsang Chin‐Fu
Published: October 2005

In the flowing fluid electric conductivity (FEC) logging method, well bore fluid is replaced with deionized water, following which FEC profiles in the well bore are measured at a series of times while the well is pumped at a constant rate. Locations where fluid enters the well bore show peaks in the FEC logs, which are analyzed to infer inflow strengths and salinities of permeable features intersected by the borehole. In multirate flowing FEC logging, the flowing FEC logging method is repeated using two or more pumping rates. The results, coupled with those of a conventional well test over the entire borehole, enable the transmissivities and inherent pressure heads of permeable features to be determined. Multirate FEC logging is carried out on a deep borehole in fractured granitic rock using three different pumping rates. Results identify 19 hydraulically conducting fractures and indicate that transmissivity, pressure head, and salinity vary significantly among them. Using three pumping rates rather than the minimum number of two permits an internal consistency check on the analysis that provides a measure of the uncertainty of the results. Good comparisons against static FEC profiles and against independent chemical, geological, and hydrogeological data have further enhanced confidence in the results of the multirate flowing FEC logging method.
Modeling catchment erosion after wildfires in the San Gabriel Mountains of southern California
Authors: Rulli M. Cristina , Rosso Renzo
Published: October 2005

The analysis of sediment data summarized for nine debris basins in Southern California shows that wildfires substantially increase erosion. However, the transient nature of this effect makes it difficult to assess the potential effect of wildfire from data analysis only. Therefore, a physically based simulation model having fine spatial and temporal resolution is used to predict the hydrologic and sediment fluxes from small burned and unburned catchments in the San Gabriel Mountains. These simulation runs show that fire significantly modifies the hydrologic response, especially sediment production which was increased from 7 to 35 times as a result of fire. The substantial increase in runoff and erosion following fire has also an impact on the hazards associated with the accelerated downstream flooding and debris flows.
River restoration
Authors: Wohl Ellen , Angermeier Paul L. , Bledsoe Brian , Kondolf G. Mathias , MacDonnell Larry , Merritt David M. , Palmer Margaret A. , Poff N. LeRoy , Tarboton David
Published: October 2005

River restoration is at the forefront of applied hydrologic science. However, many river restoration projects are conducted with minimal scientific context. We propose two themes around which a research agenda to advance the scientific basis for river restoration can be built. First, because natural variability is an inherent feature of all river systems, we hypothesize that restoration of process is more likely to succeed than restoration aimed at a fixed end point. Second, because physical, chemical, and biological processes are interconnected in complex ways across watersheds and across timescales, we hypothesize that restoration projects are more likely to be successful in achieving goals if undertaken in the context of entire watersheds. To achieve restoration objectives, the science of river restoration must include (1) an explicit recognition of the known complexities and uncertainties, (2) continued development of a theoretical framework that enables us to identify generalities among river systems and to ask relevant questions, (3) enhancing the science and use of restoration monitoring by measuring the most effective set of variables at the correct scales of measurement, (4) linking science and implementation, and (5) developing methods of restoration that are effective within existing constraints. Key limitations to river restoration include a lack of scientific knowledge of watershed‐scale process dynamics, institutional structures that are poorly suited to large‐scale adaptive management, and a lack of political support to reestablish delivery of the ecosystem amenities lost through river degradation. This paper outlines an approach for addressing these shortcomings.
Evidence that the plant cannabinoid Δ9‐tetrahydrocannabivarin is a cannabinoid CB1and CB2receptor antagonist
Authors: Thomas Adèle , Stevenson Lesley A , Wease Kerrie N , Price Martin R , Baillie Gemma , Ross Ruth A , Pertwee Roger G
Published: October 2005

Δ9‐tetrahydrocannabivarin (THCV) displaced [3H]CP55940 from specific binding sites on mouse brain and CHO‐hCB2cell membranes (Ki=75.4 and 62.8 nM, respectively).

THCV (1 μM) also antagonized CP55940‐induced stimulation of [35S]GTPγS binding to these membranes (apparentKB=93.1 and 10.1 nM, respectively).

In the mouse vas deferens, the ability of Δ9‐tetrahydrocannabinol (THC) to inhibit electrically evoked contractions was antagonized by THCV, its apparentKB‐value (96.7 nM) approximating the apparentKB‐values for its antagonism of CP55940‐ andR‐(+)‐WIN55212‐induced stimulation of [35S]GTPγS binding to mouse brain membranes.

THCV also antagonizedR‐(+)‐WIN55212, anandamide, methanandamide and CP55940 in the vas deferens, but with lower apparentKB‐values (1.5, 1.2, 4.6 and 10.3 nM, respectively).

THCV (100 nM) did not oppose clonidine, capsaicin or (−)‐7‐hydroxy‐cannabidiol‐dimethylheptyl‐induced inhibition of electrically evoked contractions of the vas deferens.

Contractile responses of the vas deferens to phenylephrine hydrochloride orβ,γ‐methylene‐ATP were not reduced by 1 μMTHCV orR‐(+)‐WIN55212, suggesting that THCV interacts withR‐(+)‐WIN55212 at prejunctional sites.

At 32 μM, THCV did reduce contractile responses to phenylephrine hydrochloride andβ,γ‐methylene‐ATP, and above 3 μMit inhibited electrically evoked contractions of the vas deferens in an SR141716A‐independent manner.

In conclusion, THCV behaves as a competitive CB1and CB2receptor antagonist. In the vas deferens, it antagonized several cannabinoids more potently than THC and was also more potent against CP55940 andR‐(+)‐WIN55212 in this tissue than in brain membranes. The bases of these agonist‐ and tissue‐dependent effects remain to be established.

British Journal of Pharmacology(2005)146, 917–926. doi:10.1038/sj.bjp.0706414
Side-chain effects in molecular electronic devices
Authors: Ernzerhof Matthias , Zhuang Min , Rocheleau Philippe
Published: October 2005

We discuss the effect of an abundant structural element of molecules on the transmission probabilities of molecular electronic devices. We show that an attachment of side chains to a molecular conductor may lead to zero transmission probabilities. The gaps in the transmission-probability appear approximately at the eigenvalues of the isolated side chains, provided that the corresponding eigenstates are not localized away from the molecular conductor. Simple Hückel-type calculations serve to illustrate the described effect. Furthermore, we show that complex transmission-probability curves, obtained with Kohn-Sham density-functional theory, also exhibit the described side-chain effect.
On three-dimensionality and control of incompressible cavity flow
Authors: Suponitsky Victoria , Avital Eldad , Gaster Mike
Published: October 2005

The incompressible large eddy simulation technique, coupled with the Lighthill-Curle acoustic analogy, is used to investigate the oscillation mechanism and sound source of a two-dimensional cavity with a length-to-depth ratio of L∕D=4 and Reynolds number of ReD=5000. It is demonstrated that the development of the three-dimensional flow field, initiated by the introduction of a random inflow disturbance, is eventually accompanied by transition from the wake to the shear layer oscillation mode, regardless of the amplitude and shape of the inflow disturbance. Once the transition to the shear layer mode is accomplished, the amplitude and frequency of oscillations are not very sensitive to the particular shape of the inflow disturbance. The effectiveness of controlling the flow oscillations by applying simultaneous steady injection and suction through the front and rear cavity walls, respectively, is demonstrated. The results show that, for injection levels exceeding a certain threshold value, the oscillations are quenched, and for levels below that value, the oscillation process is virtually unaffected. The major difference between the averaged uncontrolled and controlled velocity fields is the amount of reverse flow in the rear part of the cavity. With the aid of linear stability analysis, it is demonstrated that for injection levels leading to the quenching of the oscillations the mean velocity profiles in the cavity region are only convectively unstable, whereas for the uncontrolled case there is an absolutely unstable region. This suggests that, at least for incompressible flow, the reduction of the reverse flow inside the cavity can reduce or eliminate the oscillation process.
Efficient pure blue electroluminescence from ter(9,9, 9″,9″-bihexyl-9′,9′-diphenyl)-fluorenes
Authors: Cheng Gang , Zhang Yingfang , Zhao Yi , Liu Shiyong , Tang Shi , Ma Yuguang
Published: October 2005

An oligomer of polyfluorene, ter(9,9, 9″,9″-bihexyl-9′,9′-diphenyl)fluorenes (THPF), is used as a blue-emitting material to achieve efficient pure blue electroluminescence. Based on a 4,4′,4″-tri(N-carbazolyl)-triphenylamine hole-transporting layer, a 2,9-dimethyl-4,7-diphenyl-1,10-phenanthroline hole-blocking layer, an (8-hydroxyquinoline) aluminum electron-transporting layer, and a LiF∕Al cathode, the device has two emission peaks at 404 and 424nm, chromaticity coordinates at (0.18, 0.09), and a maximum efficiency of 1.27cd∕A. By using a submonolayer of 5,6,11,12-tetraphenylnaphthacene as a carrier detector, we demonstrate that THPF functions well as an electron-transporting layer, similar to Alq.
Dependence of carrier mobility on grain mosaic spread in ⟨001⟩-oriented Si films grown on polycrystalline substrates
Authors: Choi Woong , Matias Vladimir , Lee Jung-Kun , Findikoglu Alp T.
Published: October 2005

We studied the dependence of carrier mobility on grain mosaic spread for ⟨001⟩-oriented, 200-to-400-nm-thick Si thin films grown on polycrystalline metal substrates. The Hall mobility increased from 1% to 23% of that in bulk single-crystal Si with decreasing grain mosaic spread from 14° to 2°. For the same range of parameters, a model combining intragrain and grain boundary scattering yielded a decrease of the energy barrier height from 0.1eV to less than 10−3eV and an accompanying decrease of trap density from 6×1011cm−2 to less than 3×1010cm−2. These results demonstrate that, for polycrystalline Si films, improving the intergrain alignment is an effective and practical alternative to increasing the grain size to achieve enhanced mobility.
SIMAP—The similarity matrix of proteins
Authors: Arnold Roland , Rattei Thomas , Tischler Patrick , Truong Minh-Duc , Stümpflen Volker , Mewes Werner
Published: October 2005

Motivation: Sequence similarity searches are of great importance in bioinformatics. Exhaustive searches for homologous proteins in databases are computationally expensive and can be replaced by a database of pre-calculated homologies in many cases. Retrieving similarities from an incrementally updated database instead of repeatedly recalculating them should provide homologs much faster and frees computational resources for other purposes.

Results: We have implemented SIMAP—a database containing the similarity space formed by almost all amino acid sequences from public databases and completely sequenced genomes. The database is capable of handling very large datasets and allows incremental updates. We have implemented a powerful backbone for similarity computation, which is based on FASTA heuristics. By providing WWW interfaces as well as web services, we make our data accessible to the worldwide community. We have also adapted procedures to detect putative orthologs as example applications.

Availability: The SIMAP portal page providing links to SIMAP services is publicly available: http://mips.gsf.de/services/analysis/simap/. The web services can be accessed under http://mips.gsf.de/proj/hobitws/services/RPCSimapService?wsdl and http://mips.gsf.de/proj/hobitws/services/DocSimapService?wsdl

Contact:  t.rattei@wzw.tum.de
ARTS: alignment of RNA tertiary structures
Authors: Dror Oranit , Nussinov Ruth , Wolfson Haim
Published: October 2005

Motivation: A fast growing number of non-coding RNAs have recently been discovered to play essential roles in many cellular processes. Similar to proteins, understanding the functions of these active RNAs requires methods for analyzing their tertiary structures. However, in contrast to the wide range of structure-based approaches available for proteins, there is still a lack of methods for studying RNA structures.

Results: We present a new computational method named ARTS (alignment of RNA tertiary structures). The method compares two nucleic acid structures (RNAs or DNAs) and detects a-priori unknown common substructures. These substructures can be either large global folds containing hundreds and even thousands of nucleotides or small local tertiary motifs with at least two successive base pairs. To the best of our knowledge, this is the first method of this type. The method is highly-efficient and was used to conduct an all-against-all comparison of all the RNA structures currently available in the Protein Data Bank.

Availability: The program, a web-server and supplementary information are available on http://bioinfo3d.cs.tau.ac.il/ARTS

Contact:  oranit@post.tau.ac.il
Non-coding RNAs in Ciona intestinalis
Authors: Missal Kristin , Rose Dominic , Stadler Peter F.
Published: October 2005

Motivation: The analysis of animal genomes showed that only a minute part of their DNA codes for proteins. Recent experimental results agree, however, that a large fraction of these genomes are transcribed and hence are probably functional at the RNA level. A computational survey of vertebrate genomes has predicted thousands of previously unknown ncRNAs with evolutionarily conserved secondary structures. Extending these comparative studies beyond vertebrates is difficult, however, since most ncRNAs evolve quickly at the sequence level while conserving their characteristic secondarystructures.

Results: We report on a computational screen of structured ncRNAs in the urochordate lineage based on a comparison of the genomic data from Ciona intestinalis, Ciona savignyi and Oikopleura dioica. We predict >1000 ncRNAs with an evolutionarily conserved RNA secondary structure. Of these, about a quarter are located in introns of known protein coding sequences. A few RNA motifs can be identified as known RNAs, including ∼300 tRNAs, some 100 snRNA genes and a few microRNAs and snoRNAs.

Availability:  www.bioinf.uni-leipzig.de/Publications/SUPPLEMENTS/05-008/

Contact:  kristin@bioinf.uni-leipzig.de
Finding exact optimal motifs in matrix representation by partitioning
Authors: Leung Henry C. M. , Chin Francis Y. L.
Published: October 2005

Motivation: Finding common patterns, or motifs, in the promoter regions of co-expressed genes is an important problem in bioinformatics. A common representation of the motif is by probability matrix or PSSM (position specific scoring matrix). However, even for a motif of length six or seven, there is no algorithm that can guarantee finding the exact optimal matrix from an infinite number of possible matrices.

Results: This paper introduces the first algorithm, called EOMM, for finding the exact optimal matrix-represented motif, or simply optimal motif. Based on branch-and-bound searching by partitioning the solution space recursively, EOMM can find the optimal motif of size up to eight or nine, and a motif of larger size with any desired accuracy on the principle that the smaller the error bound, the longer the running time. Experiments show that for some real and simulated data sets, EOMM finds the motif despite very weak signals when existing software, such as MEME and MITRA-PSSM, fails to do so.

Availability:

Contact:  cmleung2@cs.hku.hk
Analyzing microarray data using quantitative association rules
Authors: Georgii Elisabeth , Richter Lothar , Rückert Ulrich , Kramer Stefan
Published: October 2005

Motivation: We tackle the problem of finding regularities in microarray data. Various data mining tools, such as clustering, classification, Bayesian networks and association rules, have been applied so far to gain insight into gene-expression data. Association rule mining techniques used so far work on discretizations of the data and cannot account for cumulative effects. In this paper, we investigate the use of quantitative association rules that can operate directly on numeric data and represent cumulative effects of variables. Technically speaking, this type of quantitative association rules based on half-spaces can find non-axis-parallel regularities.

Results: We performed a variety of experiments testing the utility of quantitative association rules for microarray data. First of all, the results should be statistically significant and robust against fluctuations in the data. Next, the approach should be scalable in the number of variables, which is important for such high-dimensional data. Finally, the rules should make sense biologically and be sufficiently different from rules found in regular association rule mining working with discretizations. In all of these dimensions, the proposed approach performed satisfactorily. Therefore, quantitative association rules based on half-spaces should be considered as a tool for the analysis of microarray gene-expression data.

Availability: The code is available from the authors on request.

Contact:  kramer@in.tum.de
Lineage-specific gene loss following mitochondrial endosymbiosis and its potential for function prediction in eukaryotes
Authors: Gabaldón Toni , Huynen Martijn A.
Published: October 2005

Motivation: The endosymbiotic origin of mitochondria has resulted in a massive horizontal transfer of genetic material from an alpha-proteobacterium to the early eukaryotes. Using large-scale phylogenetic analysis we have previously identified 630 orthologous groups of proteins derived from this event. Here we show that this proto-mitochondrial protein set has undergone extensive lineage-specific gene loss in the eukaryotes, with an average of three losses per orthologous group in a phylogeny of nine species. This gene loss has resulted in a high variability of the alphaproteobacterial-derived gene content of present-day eukaryotic genomes that might reflect functional adaptation to different environments. Proteins functioning in the same biochemical pathway tend to have a similar history of gene loss events, and we use this property to predict functional interactions among proteins in our set.

Contact:  T.Gabaldon@cmbi.ru.nl

Supplementary information: Sequences and trees for the selected orthologous groups can be accessed at http://www.cmbi.kun.nl/~jagabald/table_groupsb.html
Discriminating between rate heterogeneity and interspecific recombination in DNA sequence alignments with phylogenetic factorial hidden Markov models
Authors: Husmeier Dirk
Published: October 2005

Motivation: A recently proposed method for detecting recombination in DNA sequence alignments is based on the combination of hidden Markov models (HMMs) with phylogenetic trees. Although this method was found to detect breakpoints of recombinant regions more accurately than most existing techniques, it inherently fails to distinguish between recombination and rate variation. In the present paper, we propose to marry the phylogenetic tree to a factorial HMM (FHMM). The states of the first hidden chain represent tree topologies, whereas the states of the second independent hidden chain represent different global scaling factors of the branch lengths. Inference is done in terms of a hierarchical Bayesian model, where parameters and hidden states are sampled from the posterior distribution with Gibbs sampling.

Results: We have tested the proposed model on various synthetic and real-world DNA sequence alignments. The simulation results suggest that as opposed to the standard phylogenetic HMM, the phylogenetic FHMM clearly distinguishes between recombination and rate heterogeneity and thereby avoids the prediction of spurious recombinant regions.

Availability: The proposed method has been implemented in a MATLAB package that extends Kevin Murphy's HMM toolbox. Software and data used in our study are available from http://www.bioss.sari.ac.uk/~dirk/Supplements

Contact:  dirk@bioss.ac.uk
Recovering haplotype structure through recombination and gene conversion
Authors: Lajoie Mathieu , El-Mabrouk Nadia
Published: October 2005

Motivation: Understanding haplotype evolution subject to mutation, recombination and gene conversion is fundamental to understand genetic specificities of human populations and hereditary bases of complex disorders. The goal of this project is to develop new algorithmic tools assisting the reconstruction of historical relationships between haplotypes and the inference of haplotypes from genotypes.

Results: We present two new algorithms. The first one finds an optimal pathway of mutations, recombinations and gene conversions leading to a given haplotype of size m from a population of h haplotypes. It runs in time O(mhs2), where s is the maximum number of contiguous sites that can be exchanged in a single gene conversion. The second one finds an optimal pathway of mutations and recombinations leading to a given genotype, and runs in time O(mh2). Both algorithms are based on a penalty score model and use a dynamic programming approach. We apply the second one to the problem of inferring haplotypes from genotypes, and show how it can be used as an independent tool, or to improve the performance of existing methods.

Availability: The algorithms have been implemented in JAVA and are available on request.

Contact:  mabrouk@iro.umontreal.ca
Knowledge-based framework for hypothesis formation in biochemical networks
Authors: Tran Nam , Baral Chitta , Nagaraj Vinay J. , Joshi Lokesh
Published: October 2005

Motivation: The current knowledge about biochemical networks is largely incomplete. Thus biologists constantly need to revise or extend existing knowledge. The revision and/or extension are first formulated as theoretical hypotheses, then verified experimentally. Recently, biological data have been produced in great volumes and in diverse formats. It is a major challenge for biologists to process these data to reason about hypotheses. Many computer-aided systems have been developed to assist biologists in undertaking this challenge. The majority of the systems help in finding ‘pattern’ in data and leave the reasoning to biologists. A few systems have tried to automate the reasoning process of hypothesis formation. These systems generate hypotheses from a knowledge base and given observations. A main drawback of these knowledge-based systems is the knowledge representation formalisms they use. These formalisms are mostly monotonic and are now known to be not quite suitable for knowledge representation, especially in dealing with the inherently incomplete knowledge about biochemical networks.

Results: We present a knowledge-based framework for hypothesis formation for biochemical networks. The framework has been implemented by extending BioSigNet-RR—a knowledge based system that supports elaboration-tolerant representation and non-monotonic reasoning. Features of the extended system are illustrated by a case study of the p53 signal network.

Availability:  http://www.biosignet.org

Contact:  namtran@asu.edu
Growing Bayesian network models of gene networks from seed genes
Authors: Peña J. M. , Björkegren J. , Tegnér J.
Published: October 2005

Motivation: For the last few years, Bayesian networks (BNs) have received increasing attention from the computational biology community as models of gene networks, though learning them from gene-expression data is problematic. Most gene-expression databases contain measurements for thousands of genes, but the existing algorithms for learning BNs from data do not scale to such high-dimensional databases. This means that the user has to decide in advance which genes are included in the learning process, typically no more than a few hundreds, and which genes are excluded from it. This is not a trivial decision. We propose an alternative approach to overcome this problem.

Results: We propose a new algorithm for learning BN models of gene networks from gene-expression data. Our algorithm receives a seed gene S and a positive integer R from the user, and returns a BN for the genes that depend on S such that less than R other genes mediate the dependency. Our algorithm grows the BN, which initially only contains S, by repeating the following step R + 1 times and, then, pruning some genes; find the parents and children of all the genes in the BN and add them to it. Intuitively, our algorithm provides the user with a window of radius R around S to look at the BN model of a gene network without having to exclude any gene in advance. We prove that our algorithm is correct under the faithfulness assumption. We evaluate our algorithm on simulated and biological data (Rosetta compendium) with satisfactory results.

Contact:  jmp@ifm.liu.se