bluuebunny/crossref_metadata_2025 huggingface dataset:
Dynamic deformation of migratory efferent lymph‐derived cells “trapped” in the inflammatory microcirculation
Authors: Su Mei , West Charles A. , Young Alan J. , He Chufa , Konerding Moritz A. , Mentzer Steven J.
Published: November 2002

The cellular immune response depends on the delivery of lymphocytes from the lymph node to the peripheral site of antigenic challenge. During their passage through the inflammatory microcirculaton, the migratory cells can become transiently immobilized or “trapped” in small caliber vessels. In this report, we used intravital microscopy and temporal area mapping to define the dynamic deformation of efferent lymph‐derived mononuclear cells trapped in the systemic inflammatory microcirculation. Mononuclear cells obtained from the efferent lymph draining the oxazolone‐stimulated microcirculation were labeled with fluorescent dye and reinjected into the feeding arterial circulation. Intravital video microscopy observed thousands of cells passing through the microcirculation; 35 cells were “trapped” in the oxazolone‐stimulated microcirculation. Temporal area maps of the trapped cells demonstrated dramatic slowing and deformation. The cells were trapped in the microcirculation for a median of 8.90 sec (range 5–17 sec) prior to returning to the flow stream. During this period, the cells showed sustained movement associated with both antegrade locomotion (mean cell velocity = 7.92 μm/sec; range 1.16–14.23 μm/sec) and dynamic elongation (median cell length = 73.8 μm; range 58–144 μm). In contrast, efferent lymph‐derived cells passing unimpeded through the microcirculation demonstrated rapid velocity (median velocity = 216 μm/sec) and spherical geometry (median diameter = 14.6 μm). Further, the membrane surface area of the “trapped” cells, calculated based on digital image morphometry and corrosion cast scanning electron microscopy, suggested that the fractional excess membrane of the cells in the efferent lymph was significantly greater than previous estimates of membrane excess. These data indicate that transient immobilization of efferent lymph‐derived mononuclear cells in the systemic inflammatory microcirculation is rare. When “trapping” does occur, the shape changes and sustained cell movement facilitated by excess cell membrane may contribute to the return of the “trapped cells” into the flow stream. © 2002 Wiley‐Liss, Inc.
Rap1 reverses transcriptional repression of TGF‐β type II receptor by a mechanism involving AP‐1 in the human pancreatic cancer cell line, UK Pan‐1
Authors: Fralix Kimberly D. , Zhao Shujie , Venkatasubbarao Kolaparthi , Freeman James W.
Published: November 2002

The TGF‐β signaling pathway has potent anti‐mitogenic effects in epithelial cells and loss of negative growth regulation is often associated with increased tumorigenicity. The human pancreatic ductal adenocarcinoma cell line, UK Pan‐1, which expresses DPC4, is not highly responsive to TGF‐β due to transcriptional repression of TGF‐β type II receptor (RII). Here, we show that UK Pan‐1 cells transfected with a plasmid to overexpress rap1 protein (UK/rap1) causes an increase in RII transcription and restores sensitivity to TGF‐β growth inhibition. The overexpression of rap1 was associated with diminished ras signaling as measured by ras binding domain (RBD)‐binding assays. Electrophoretic mobility shift assays (EMSA) analysis revealed increased binding of nuclear proteins to a previously identified positive regulatory element (PRE1) of the RII promoter in rap1 transfected cells. Competition with an oligo containing the AP‐1 consensus site was able to inhibit this binding of nuclear proteins to the PRE1 region. Further EMSA analysis using antibodies to various AP‐1 components revealed that junB antibodies partially depleted the increase in binding to the PRE1 seen in UK/rap1 cells while antibodies to other AP‐1 constituents such as c‐jun, c‐fos, and ATF‐1 had no effect on binding. Consistent with this data, transient transfection of UK Pan‐1 cells with junB resulted in greater RII transcription (twofold) as measured by RII‐luciferase assay. Mutation of the AP‐1 site inhibited junB‐mediated or rap1‐mediated increases in RII promoter activity. These data suggest that rap1 signaling may mediate an increase in RII transcription via increased binding of nuclear factors including junB to the PRE1 region of the RII promoter. © 2002 Wiley‐Liss, Inc.
Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR‐TKIs): Simple drugs with a complex mechanism of action?
Authors: Normanno Nicola , Maiello Monica R. , De Luca Antonella
Published: November 2002

A range of target‐based agents for the treatment of solid tumors are in development. The epidermal growth factor receptor (EGFR) has been identified as a relevant target as it is involved in regulating several cellular functions important in the proliferation and survival of cancer cells, is commonly expressed at high levels in a range of tumors, and high expression is often related to poor prognosis. EGFR is a member of the ErbB family of receptors which also includes ErbB‐2, ErbB‐3, and ErbB‐4. These receptors form dimers of the same type (homodimers) or with other family members (heterodimers), each combination resulting in different downstream effects. Some of the most advanced targeted agents in development are the EGFR tyrosine kinase inhibitors (EGFR‐TKIs), of which ZD1839 (‘Iressa’) is an example. In Phase II monotherapy trials, oral ZD1839 was well tolerated and demonstrated clinically meaningful antitumor activity and symptom relief in pretreated patients with advanced NSCLC. Preclinical studies have suggested that the antitumor activity of ZD1839 does not depend on the level of EGFR expression. Furthermore, in addition to an effect on EGFR signaling, treatment with ZD1839 as well as with other quinazoline EGFR‐TKIs, may also affect signaling of other ErbB family members. EGFR‐TKIs have been shown in preclinical studies to increase the efficacy of cytotoxic drugs and Phase III trials of such combinations are ongoing. On the basis that different signal transduction pathways contribute to the control of tumor growth, future therapeutic approaches are likely to involve combination of different targeted agents. © 2002 Wiley‐Liss, Inc.
Improved design and optimization models for the fixed bed adsorption of acid dye and zinc ions from effluents
Authors: Ko Danny C K , Lee Vinci K C , Porter John F , McKay Gordon
Published: December 2002

The bed depth service time (BDST) design model, which accounts for the change of bed adsorption capacity with service time, has been modified to expand its application and overcome the limiting assumptions of the original BDST analysis. Column experiments were undertaken to test the new model for two adsorption systems, namely zinc ion–bone char and Acid Blue 80 dye‐activated carbon. It was found that the percentage of saturation capacity could be correlated using a square‐root dependence on the service time and this correlation was incorporated into the original BDST analysis to replace the total sorption capacity term, giving the model a much wider application to real systems. The empty bed residence time optimization approach was modified using the same time‐dependent capacity expression and was successfully applied to the metal ion–bone char and the dye‐activated carbon system with the use of equilibrium saturated bed capacity. These modifications to the BDST design model and the EBRT optimization model will give more accurate scale‐up data for the design of large‐scale column adsorption systems.

© 2002 Society of Chemical Industry
Critical evaluation of the chemical standardization procedure for measuring gastric emptying of solids
Authors: Goethals P. , Volkaert A. , Van Vlem B. , Vanholder R.
Published: November 2002

The purpose of this study was to evaluate the baking process of yolk spiked with octanoate to measure gastric emptying rate of solids. [1‐11C]octanoate was produced by the reaction of [11C]CO2 with heptyl magnesium bromide in tetrahydrofuran (THF), followed by purification with HPLC. The decay corrected radiochemical yield ranged from 24 to 38% (5.9–9.8 GBq EOS, synthesis time: 25 min; specific radioactivity ∼90 GBq μmol−1). To check the evaporation of [1‐11C]octanoate during the baking process of yolk, [1‐11C]octanoate or potassium [1‐11C]octanoate, respectively, was added. An important fraction of the acid evaporated while for the potassium [1‐11C]octanoate <10% disappeared. Conclusion: potassium (1‐13C)octanoate is a better tracer than (1‐13C) octanoate to study gastroenterological phenomena. Copyright © 2002 John Wiley & Sons, Ltd.
Synthesis of 32P‐labeled intermediates on the purine biosynthetic pathway
Authors: Mehl Ryan A. , Begley Tadhg P.
Published: November 2002

A fast and efficient route to 32P‐labeled intermediates on the purine biosynthetic pathway is described. Adenosine kinase catalyzes the phosphorylation of 5‐aminoimidazole‐4‐carboxamide ribonucleoside (AICARs) to give [32P]‐5‐aminoimidazole‐4‐carboxamide ribonucleotide (AICAR). This was then hydrolyzed to [32P]‐4‐carboxy‐5‐aminoimidazole ribonucleotide (CAIR). Treatment of CAIR with N5‐CAIR mutase gave [32P]‐5‐aminoimidazole ribonucleotide (AIR) in milligram quantities. Copyright © 2002 John Wiley & Sons, Ltd.
Ortho‐[18F]Fluoronitrobenzenes by no‐carrier‐added nucleophilic aromatic substitution with K[18F]F–K222—A comparative study
Authors: Karramkam M. , Hinnen F. , Bramoullé Y. , Jubeau S. , Dollé F.
Published: November 2002

The scope of the nucleophilic aromatic ortho‐fluorinations from the corresponding ortho‐halonitrobenzene precursors (halo‐to‐fluoro substitutions) with no‐carrier‐added [18F]fluoride ion as its activated K[18F]F–K222 complex has been evaluated via the radiosynthesis of ortho‐[18F]fluoronitrobenzene, chosen as a model reaction. The parameters studied include the influence of the leaving group in the ortho position of the phenyl ring (–Cl, –Br, –l), the quantity of precursor used, the type of activation (conventional heating or microwave irradiations), the solvent, the temperature and the reaction time. The iodo‐precursor was completely unreactive and the bromo‐precursor gave only low incorporation (<10%) in the optimal conditions used (conventional heating at 145°C or microwave activation, 100 W for 120 s). Only the chloro‐precursor was found reactive in the conditions described above and up to 70% yield was observed for the formation of ortho‐[18F]fluoronitrobenzene ([18F]‐1). In all the experiments, the unwanted ortho‐[18F]fluoro‐halobenzenes, potentially resulting from the nitro‐to‐fluoro substitution, could not be detected. These results will be applied for the radiosynthesis of 5‐[18F]fluoro‐6‐nitroquipazine, a potent radioligand for the imaging of the serotonin transporter with PET. Copyright © 2002 John Wiley & Sons, Ltd.
Synthesis of [14C]‐labelled repinotan hydrochloride and its major metabolite M‐6
Authors: Seidel D. , Conrad M. , Schoof Y. , Schohe‐Loop R.
Published: November 2002

For studies of pharmacokinetics and drug metabolism of the new 5‐HT1A agonist repinotan, the 14C‐labelled version was synthesized. Starting from [U‐14C]phenol, a 10‐step synthesis led to 457 mg (1.58 GBq) of [U‐14C]repinotan hydrochloride, labelled uniformly in the aromatic ring of the chromane moiety. For a study in man, a mono‐carbon‐14 labelled substance was required. Therefore a 7‐step synthesis was performed starting from [carbonyl‐14C]2‐hydroxy‐acetophenone. The yield was 106 mg (0.396 GBq) of [4‐chromane‐14C]repinotan hydrochloride. The carbon‐14 labelled major metabolite, hydroxylated in the 6‐position of the chromane moiety, was synthesised as reference compound. Copyright © 2002 John Wiley & Sons, Ltd.
Synthesis of (±) [5‐3H] N′‐nitrosoanatabine, a tobacco‐specific nitrosamine
Authors: Desai Dhimant , Lin Guoying , Morimoto Hiromi , Williams Philip G. , Bayoumy Karam El‐ , Amin Shantu
Published: November 2002

Tobacco‐specific N′‐nitrosamines (TSNA) are a unique class of systemic organ‐specific carcinogens. The TSNA are formed by N‐nitrosation of nicotine and of the minor tobacco alkaloids after harvesting of tobacco and during smoking. The N‐nitrosation of anatabine leads to N′‐nitrosoanatabine (NAT; 1‐nitroso‐1,2,3,4‐tetrahydro‐2,3'‐bipyridyl) which requires in‐depth assays in laboratory animals other than the rat. Furthermore, delineation of its tissue distribution and metabolism is needed for structure:activity comparisons with other TSNA and for the assessment of potential human risk from this TSNA. We have, therefore, synthesized (±)[5‐3H]NAT. 5‐Bromo‐3‐pyridine‐carboxaldehyde was condensed with ethyl carbamate prior to Diels–Alder reaction with 1,4‐butadiene to give the racemic anatabine ring system. Hydrolysis, followed by reduction with LiAlT4 and nitrosation, led to (±)[5‐3H]NAT (60% yield, specific activity 266 mCi/mmol, radiochemical purity of >99%). Copyright © 2002 John Wiley & Sons, Ltd.
Synthesis of 14C‐labeled 4‐hydroxyindole as an intermediate for the preparation of (S)‐2‐[4‐[2‐[3‐(indol‐2‐[14C]‐4‐yloxy)‐2‐hydroxypropylamino]‐2‐methylpropyl]‐phenoxy]pyridine‐5‐carboxamide (LY368842‐[indole‐14C]) glycolate
Authors: Czeskis Boris A. , Clodfelter Dean K. , Wheeler William J.
Published: November 2002

Synthesis of 4‐hydroxyindole labeled with 14C at the 2‐position was accomplished based on the vicarious nucleophilic substitution reaction of benzyl‐protected 3‐nitrophenol with p‐chlorophenoxyacetonitrile‐[1‐14C]. This was followed by the reductive cyclization of o‐nitrocyanomethyl derivative by palladium catalyzed hydrogenation. p‐Chlorophenoxyacetonitrile‐[1‐14C] was prepared from commercially available p‐chlorophenoxymethyl chloride and sodium cyanide‐[14C]. 4‐Hydroxyindole‐[2‐14C] was used for the synthesis of 14C‐labeled β3 adrenergic agonist LY368842. Copyright © 2002 John Wiley & Sons, Ltd.
Synthesis of [2H3]‐dextromethorphan and its major urinary metabolites [2H3]‐dextrorphan and [2H3]‐dextrorphan‐β‐glucuronide
Authors: Heinkele Georg , Schänzle Gerhard , Mürdter Thomas E.
Published: November 2002

Starting from dextromethorphan, [2H3]‐dextrorphan‐β‐glucuronide was synthesized in four steps with [2H3]‐dextromethorphan and [2H3]‐dextrorphan as intermediates with an overall yield of 11%. Copyright © 2002 John Wiley & Sons, Ltd.
10th Conference of the Central European Division e.V. of the International Isotope Society
Authors: Jones J R , Lu S‐Y , Shevchenko V. P. , Nagaev I. Yu. , Myasoedov N. F. , Susan A. B. , Anderskerskevitz R. , Birke F. W. , Switek K‐H. , Wiegerinck Peter , Post Olaf , Hofstede Leontine , van den Heuvel Marcel , Pleiss U. , Seidel D. , Switek K.‐H. , Braunger H. , Seidel Dietrich , Schlecker Rainer , Moenius Thomas , Seiler Max‐Peter , Nozulak Joachim , Burtscher Paul , Almi Mario , Guelfi Simone , Navacchia Maria Luisa , Felicini C. , Giribone D. , Pignatti A. , Fontana E. , Pignatti A. , Fontana E. , McGrath J. W. , Peric Simov B. , Preusser W. , Quinn J. P. , Schmidt S. , Woschek A. , Wuggenig F. , Hammerschmidt F. , Spies H. , Maas Jochen , Krone Volker , Diehl Frank , Coy Johannes , Hoheisel Jörg , Doeberitz Magnus von Knebel , Nees Matthias , Klett Alfred
Published: November 2002

Use of Microwaves in Organic Synthesis: Application in the Synthesis of Isotopically Labelled Compounds

Preparation of Tritium‐Labelled BIIL 260 with High Specific Radioactivity

Synthesis of [3H]‐, [14C]‐ and [13C,2H]‐labelled Org 12962 Derivatives

Labeling of BAY 58‐2667, an Activator of sGC

Preparation and Use of [14C]N,N′‐Carbonylditriazole in the Labelling of Urea Derivatives

Efficient Carbon‐14 Labeling of 2‐(3‐Hydroxypropyl)‐1H‐benzimidazole

Synthesis of Some 14C‐Labelled Fungicides

C‐14 Labelling of NVP‐ABE651 and NVP‐ABE697

Synthesis of Carbon‐13,14 Isotopomers of a Novel 4‐Substituted‐2‐Carboxy Tetrahydroquinoline

[14C]CH2N2: A Suitable Precursor for the Preparation of 14C‐Labelled Anthracyclines

Preparative HPLC: a Useful Approach to Speed‐up the Purification of Labelled Compounds.

Use of Stable Isotopes for the Biosynthesis and Biodegradation of Fosfomycin

Metalloradiopharmaceuticals for Nuclear Medicine

Strategic outlook: Future Methods in DMPK and subsequent requirements for isotopically labelled compounds

Isotopic Imaging of Glass‐based cDNA Microarray Hybridization

New Developments in Radiation Measuring Technique
Congener‐specific determination of dioxins and related compounds by gas chromatography coupled to LRMS, HRMS, MS/MS and TOFMS
Authors: Eljarrat E. , Barceló D.
Published: November 2002

Their characteristics as persistent organic pollutant and their toxicity (2,3,7,8‐TCDD is named as a known human carcinogen) make the dioxins and related compounds a focus of interest in environmental analytical chemistry. In view of the widespread distribution of dioxins in the environment, these compounds must be monitored in several matrices, such as air, effluents, soil, sludge and biological samples. The analytical methodologies are especially difficult owing to the complexity of the mixtures of congeners (210 PCDD/Fs and 209 PCBs) and to the low detection limits required (ppb to ppq). Moreover, time‐consuming sample preparation steps are needed owing to the presence of a large number of interfering compounds. The different toxicity of each congener requires the development of congener specific methods. This review of trace dioxin determination by mass spectrometry (MS) includes sample preparation and chromatographic separation. In this Special Feature, the use of different MS techniques such as low‐resolution MS (LRMS) and high‐resolution MS (HRMS) is discussed in terms of selectivity and sensitivity. The performances of other MS techniques, such as tandem MS (MS/MS) and time‐of‐flight MS (ToFMS), are compared. Quantification techniques, especially the isotopic dilution method, are also discussed. Conclusions and future perspectives are outlined. Copyright © 2002 John Wiley & Sons, Ltd.
Ionization energy reductions in small 2,5‐dihydroxybenzoic acid–proline clusters
Authors: Kinsel Gary R. , Knochenmuss Richard , Setz Patrick , Land C. Mark , Goh Sor‐Koon , Archibong Edet F. , Hardesty Jon H. , Marynick Dennis S.
Published: November 2002

The photoionization of (pro)nDHB (pro = proline, DHB = 2,5‐dihydroxybenzoic acid, n = 0, 1, 2 or 4) clusters was studied both experimentally and computationally. Experimentally the (pro)nDHB clusters are generated in the gas phase by laser desorption and supersonic jet entrainment. The photoionization thresholds are then determined by the mass‐selective measurement of both one‐ and two‐color photoionization efficiency curves. These experiments demonstrate that the ionization energies (IEs) of the (pro)nDHB clusters are substantially reduced in comparison with the IE of free DHB. Computational studies of the (pro)nDHB clusters provide insights into the mechanism of IE reduction. For the (pro)DHB system the IE reduction results from spin delocalization in the ion state of the cluster. In contrast, for the (pro)2DHB and (pro)4DHB clusters the IE reduction results from an inductive delocalization of electron density from pro to DHB in the ground state of the cluster. This latter effect, which is a result of the specific hydrogen‐bonding interactions occurring in the mixed clusters, leads to IE reductions of >1 eV. Finally, determination of the energetics of the (pro)2DHB radical cation demonstrate that the DHB‐to‐proline proton transfer reaction is a barrierless, exoergic process in the ion state and that energetic demands for cluster dissociation to protonated (pro)2 plus a deprotonated DHB radical are substantially lower than those for cluster dissociation to (pro)2 plus DHB+ ·. Cumulatively, these studies provide new energetic and mechanistic insights into both primary and secondary MALDI ionization processes. Copyright © 2002 John Wiley & Sons, Ltd.
Ionization energies of multiply protonated polypeptides obtained by tandem ionization in Fourier transform mass spectrometers
Authors: Budnik Bogdan A. , Tsybin Youri O. , Håkansson Per , Zubarev Roman A.
Published: November 2002

Ionization energies (IE) of [M + zH]z+ (z+) electrospray‐produced polypeptides were determined by electron ionization in a Penning cell of 4.7 and 9.4 T Fourier transform mass spectrometers. For z = 1+ and substance P, the found IE value of 11.0 ± 0.4 eV is in agreement with that obtained earlier for ions generated with matrix‐assisted laser desorption/ionization. For higher z, the following values were found: 11.7 ± 0.3 eV for 2+ of [Arg‐8]‐vasopressin, 11.1 ± 0.6 eV for 2+ of substance P, 12.2 ± 0.7 eV for 2+ of renin substrate, 13.3 ± 0.4 eV for 3+ of B‐chain of insulin and 14.6 ± 0.6 eV for 4+ and 15.1 ± 0.4 eV for 5+ of melittin. It was found that 90% of existing IE data on polypeptides in the 1.0–3.5 kDa mass range are described with ≤0.5 eV uncertainty by the empirical equation IE(z) = 9.8 + 1.1z. The average IE increase of 1.1 eV/charge is attributed to Coulombic repulsion. The deduced ionization energy of a neutral polypeptide molecule, 9.8 ± 0.3 eV, is consistent with literature expectations. Copyright © 2002 John Wiley & Sons, Ltd.
Electron ionization‐induced fragmentation of R2N2Fe2(CO)6 complexes with distinct geometries of the tetrahedral core: investigation of µ‐1,2‐(1,2‐diaza‐3‐methylcyclopentane)diylbis(tricarbonyliron) and bis(µ2‐acetophenoniminato)bis(tricarbonyliron)
Authors: Zimniak Andrzej
Published: November 2002

Two binuclear bis(tricarbonyliron) title complexes with N2Fe2 tetrahedral cores, 1 and 2, respectively, which show different molecular folding resulting from the appearance (in 1), and absence (in 2) of the NN σ‐bond, were compared in terms of mass spectral fragmentation routes. A multipath fragmentation noted for the molecule 1 revealing internal stress contrasts with the single‐route fragmentation of 2. The fragmentation paths resulting from the admixtures were defined and analyzed from the fragment ion B/E and parent ion B2/E linked scan spectra. Copyright © 2002 John Wiley & Sons, Ltd.
Simultaneous determination of metabolites of trimethylbenzenes, dimethylbenzylmercapturicacid and dimethylhippuric acid, in human urine by solid‐phase extraction followed by liquid chromatography tandem mass spectrometry
Authors: Moriwaki Hiroshi , Watanabe Ayumi , Arakawa Ryuichi , Tsujimoto Yuji , Shimizu Mitsuru , Noda Tsutomu , Warashina Munehiro , Tanaka Masanobu
Published: November 2002

We describe a novel method for the determination of three kinds of dimethylbenzylmercapturic acids (DMM) and six kinds of dimethylhippuric acids (DMH), found in urine as metabolites of trimethylbenzenes, based on liquid chromatography/electrospray ionization tandem mass spectrometry. A solid‐phase extraction procedure was used for the extractions of DMM and DMH from a urine sample, and the separation was performed on a reversed–phase C30 column. The analytes were ionized by electrospray in the positive‐ion mode. Operating in the multiple reaction monitoring mode, the linearity of the relative mass spectrometric responses to the internal standard versus analyte concentrations were established in the range 0.1–100 ng ml−1. The extraction procedure was rapid and the relative standard deviations were below 5%. The detection limits of DMM and DMH in the urine by the proposed method were in the ranges 0.26–0.41 and 0.42–2.0 ng l−1, respectively. Furthermore, DMM and DMH were detected in a urine sample from an individual who did not suffer from occupational exposure to trimethylbenzenes, by using this method. Copyright © 2002 John Wiley & Sons, Ltd.
Laser desorption‐atmospheric pressure chemical ionization: a novel ion source for the direct coupling of polyacrylamide gel electrophoresis to mass spectrometry
Authors: Coon Joshua J. , Steele Heather A. , Laipis Philip J. , Harrison W. W.
Published: November 2002

Laser desorption‐atmospheric pressure chemical ionization‐mass spectrometry (LD‐APCI‐MS) is presented for the atmospheric pressure (AP) sampling of tryptic peptides directly from a polyacrylamide gel. In contrast to other gel sampling mass spectrometric approaches, this technique does not require the addition of any exogenous matrices to the gel to assist with ionization. In this arrangement, a CO2 laser at 10.6 µm is used to desorb intact neutral peptide molecules from the gel, followed by ionization in the gas‐phase with APCI. The ions are then sampled via a heated capillary inlet and transferred to a quadrupole ion trap mass spectrometer for mass analysis. Preliminary results suggest the polyacrylamide gel electrophoresis–LD‐APCI‐MS technique provides several advantages that could translate into a more convenient, robust methodology for the rapid identification and characterization of proteins. Finally, strategies regarding the further development of the method are presented. Copyright © 2002 John Wiley & Sons, Ltd.
Cool‐season precipitation in the southwestern USA sinceAD1000: comparison of linear and nonlinear techniques for reconstruction
Authors: Ni Fenbiao , Cavazos Tereza , Hughes Malcolm K. , Comrie Andrew C. , Funkhouser Gary
Published: November 2002

A 1000 year reconstruction of cool‐season (November–April) precipitation was developed for each climate division in Arizona and New Mexico from a network of 19 tree‐ring chronologies in the southwestern USA. Linear regression (LR) and artificial neural network (NN) models were used to identify the cool‐season precipitation signal in tree rings. Using 1931–88 records, the stepwise LR model was cross‐validated with a leave‐one‐out procedure and the NN was validated with a bootstrap technique. The final models were also independently validated using the 1896–1930 precipitation data. In most of the climate divisions, both techniques can successfully reconstruct dry and normal years, and the NN seems to capture large precipitation events and more variability better than the LR. In the 1000 year reconstructions the NN also produces more distinctive wet events and more variability, whereas the LR produces more distinctive dry events. The 1000 year reconstructed precipitation from the two models shows several sustained dry and wet periods comparable to the 1950s drought (e.g. 16th century mega drought) and to the post‐1976 wet period (e.g. 1330s, 1610s). The impact of extreme periods on the environment may be stronger during sudden reversals from dry to wet, which were not uncommon throughout the millennium, such as the 1610s wet interval that followed the 16th century mega drought. The instrumental records suggest that strong dry to wet precipitation reversals in the past 1000 years might be linked to strong shifts from cold to warm El Niño‐southern oscillation events and from a negative to positive Pacific decadal oscillation. Copyright © 2002 Royal Meteorological Society.
Links between circulation and changes in the characteristics of Iberian rainfall
Authors: Goodess C. M. , Jones P. D.
Published: November 2002

Investigation of the links between atmospheric circulation patterns and rainfall is important for the understanding of climatic variability and for the development of empirical circulation‐based downscaling methods. Here, spatial and temporal variations in circulation‐rainfall relationships over the Iberian Peninsula during the period 1958–97 are explored using an automated circulation classification scheme and daily rainfall totals for 18 stations. Links between the circulation classification scheme and the North Atlantic oscillation (NAO) are also considered, as are the direct links between rainfall and the NAO. Trends in rainfall and circulation‐type frequency are explored. A general tendency towards decreasing mean seasonal rainfall over the peninsula, with the exception of the southeastern Mediterranean coast, hides larger changes in wet day amount and rainfall probability. There is a tendency towards more, less‐intensive rain days across much of Iberia, with a tendency towards more, more‐intensive rain days along the southeastern Mediterranean coast, both of which are reflected in changes in rainfall amount quantiles. A preliminary analysis indicates that these changes may have occurred systematically across all circulation types. Comparison of the trends in rainfall and in circulation‐type frequency suggests possible links. These links are supported by linear regression analyses using circulation‐type frequencies as predictor variables and rainfall totals for winter months as the predictands. The selected predictor variables reflect the main circulation features influencing winter rainfall across the peninsula, i.e. the strong influence of Atlantic westerly and southwesterly airmasses over much of the peninsula, of northerly and northwesterly surface flow over northern/northwestern Spain and northern Portugal and the stronger effect of Mediterranean rather than Atlantic influences in southeastern Spain. The observed rainfall changes cannot, however, be explained by changes in circulation alone. Copyright © 2002 Royal Meteorological Society.
A graphical sensitivity analysis for statistical climate models: application to Indian monsoon rainfall prediction by artificial neural networks and multiple linear regression models
Authors: Cannon Alex J. , McKendry Ian G.
Published: November 2002

A form of sensitivity analysis is described that illustrates the effects that inputs have on outputs of statistical models. The strength and sign of relationships, the types of nonlinearity, and the presence of interactions between inputs can be diagnosed using this technique. Intended for interpreting flexible nonlinear models, the graphical sensitivity analysis is applied to artificial neural networks (ANNs) in this study. As ANNs are increasingly being used for climate prediction, the discussion focuses on specific problems associated with their use in this context. The technique is illustrated using a real‐world, long‐range climate prediction example. Principal components (PCs) of circulation fields prior to the Indian summer monsoon are related to rainfall during monsoon months for the 1958–98 period. The skill of multiple linear regression and ensemble ANNs are compared using a resampling procedure. Interpretation of the models is then conducted using traditional diagnostic tools and graphical sensitivity analysis. This provides an improved investigation of precursor circulation field–summer monsoon rainfall relationships identified in a previous modelling study. The relatively stable, linear relationship identified between the May 200 hPa geopotential height field and summer monsoon rainfall is confirmed. Correlations previously identified between 850 hPa geopotential heights during January and rainfall by ANNs are shown to be the result of a weakly nonlinear, interactive relationship involving the first and second PCs of this field. An analysis of out‐of‐sample model predictions suggests that this relationship does not persist over the entire study period. This may result from a modulation of the strength of the circulation–rainfall relationship by El Niño–southern oscillation. Stratification of the results also reveals a relatively strong, nearly linear relationship with monsoon strength during years exhibiting positive scores of the second PC. On extending the analysis to longer lead‐times, the surface pressure and 850 hPa geopotential height fields during November show relatively strong, persistent precursor relationships with summer monsoon rainfall. Sensitivity analyses suggest a mildly nonlinear relationship that is common to both fields. Copyright © 2002 Environment Canada. Published by John Wiley & Sons, Ltd.
Recent variations in seasonality of temperature and precipitation in Canada, 1976–95
Authors: Whitfield Paul H. , Bodtker Karin , Cannon Alex J.
Published: November 2002

A previously reported analysis of rehabilitated monthly temperature and precipitation time series for several hundred stations across Canada showed generally spatially coherent patterns of variation between two decades (1976–85 and 1986–95). The present work expands that analysis to finer time scales and a greater number of stations. We demonstrate how the finer temporal resolution, at 5 day or 11 day intervals, increases the separation between clusters of recent variations in seasonal patterns of temperature and precipitation. We also expand the analysis by increasing the number of stations from only rehabilitated monthly data sets to rehabilitated daily sets, then to approximately 1500 daily observation stations. This increases the spatial density of data and allows a finer spatial resolution of patterns between the two decades. We also examine the success of clustering partial records, i.e. sites where the data record is incomplete. The intent of this study was to be consistent with previous work and explore how greater temporal and spatial detail in the climate data affects the resolution of patterns of recent climate variations. The variations we report for temperature and precipitation are taking place at different temporal and spatial scales. Further, the spatial patterns are much broader than local climate regions and ecozones, indicating that the differences observed may be the result of variations in atmospheric circulation. Copyright © 2002 Environment Canada. Published by John Wiley & Sons, Ltd.
Interannual rainfall variability in the Amazon basin and sea‐surface temperatures in the equatorial Pacific and the tropical Atlantic Oceans
Authors: Ronchail Josyane , Cochonneau Gérard , Molinier Michel , Guyot Jean‐Loup , De Miranda Chaves Adriana Goretti , Guimarães Valdemar , de Oliveira Eurides
Published: November 2002

Rainfall variability in the Amazon basin is studied in relation to sea‐surface temperatures (SSTs) in the equatorial Pacific and the northern and southern tropical Atlantic during the 1977–99 period, using the HiBAm original rainfall data set and complementary cluster and composite analyses.

The northeastern part of the basin, north of 5 °S and east of 60 °W, is significantly related with tropical SSTs: a rainier wet season is observed when the equatorial Pacific and the northern (southern) tropical Atlantic are anomalously cold (warm). A shorter and drier wet season is observed during El Niño events and negative rainfall anomalies are also significantly associated with a warm northern Atlantic in the austral autumn and a cold southern Atlantic in the spring. The northeastern Amazon rainfall anomalies are closely related with El Niño–southern oscillation during the whole year, whereas the relationships with the tropical Atlantic SST anomalies are mainly observed during the autumn. A time–space continuity is observed between El Niño‐related rainfall anomalies in the northeastern Amazon, those in the northern Amazon and south‐eastern Amazon, and those in northern South America and in the Nordeste of Brazil.

A reinforcement of certain rainfall anomalies is observed when specific oceanic events combine. For instance, when El Niño and cold SSTs in the southern Atlantic are associated, very strong negative anomalies are observed in the whole northern Amazon basin. Nonetheless, the comparison of the cluster and the composite analyses results shows that the rainfall anomalies in the northeastern Amazon are not always associated with tropical SST anomalies.

In the southern and western Amazon, significant tropical SST‐related rainfall anomalies are very few and spatially variable. The precipitation origins differ from those of the northeastern Amazon: land temperature variability, extratropical perturbations and moisture advection are important rainfall factors, as well as SSTs. This could partially explain why: (a) the above‐mentioned signals weaken or disappear, with the exception of the relative dryness that is observed at the peak of an El Niño event and during the dry season when northern Atlantic SSTs are warmer than usual; (b) rainfall anomalies tend to resemble those of southeastern South America, noticeably at the beginning and the end of El Niño and La Niña events; (c) some strong excesses of rain are not associated with any SST anomalies and merit further investigation. Copyright © 2002 Royal Meteorological Society.
Atmospheric mechanisms governing the spatial and temporal variability of phenological phases in central Europe
Authors: Scheifinger Helfried , Menzel Annette , Koch Elisabeth , Peter Christian , Ahas Rein
Published: November 2002

A data set of 17 phenological phases from Germany, Austria, Switzerland and Slovenia spanning the time period from 1951 to 1998 has been made available for analysis together with a gridded temperature data set (1° × 1° grid) and the North Atlantic Oscillation (NAO) index time series. The disturbances of the westerlies constitute the main atmospheric source for the temporal variability of phenological events in Europe. The trend, the standard deviation and the discontinuity of the phenological time series at the end of the 1980s can, to a great extent, be explained by the NAO. A number of factors modulate the influence of the NAO in time and space. The seasonal northward shift of the westerlies overlaps with the sequence of phenological spring phases, thereby gradually reducing its influence on the temporal variability of phenological events with progression of spring (temporal loss of influence). This temporal process is reflected by a pronounced decrease in trend and standard deviation values and common variability with the NAO with increasing year‐day. The reduced influence of the NAO with increasing distance from the Atlantic coast is not only apparent in studies based on the data set of the International Phenological Gardens, but also in the data set of this study with a smaller spatial extent (large‐scale loss of influence). The common variance between phenological and NAO time series displays a discontinuous drop from the European Atlantic coast towards the Alps. On a local and regional scale, mountainous terrain reduces the influence of the large‐scale atmospheric flow from the Atlantic via a proposed ‘decoupling mechanism’. Valleys in mountainous terrain have the inclination to harbour temperature inversions over extended periods of time during the cold season, which isolate the valley climate from the large‐scale atmospheric flow at higher altitudes. Most phenological stations reside at valley bottoms and are thus largely decoupled in their temporal variability from the influence of the westerly flow regime (local‐scale loss of influence). This study corroborates an increasing number of similar investigations that find that vegetation does react in a sensitive way to variations of its atmospheric environment across various temporal and spatial scales. Copyright © 2002 Royal Meteorological Society.
Changes in European spring phenology
Authors: Ahas R. , Aasa A. , Menzel A. , Fedotova V. G. , Scheifinger H.
Published: November 2002

The European phyto‐phenological database of the EU 5th Framework project ‘POSITIVE’ facilitated an examination of the rate and spatial pattern of changes in spring phenology across Europe. This database was collected, evaluated and composed from different national databases of Eastern and Western Europe covering the time period 1951–1998. Results show that spring phases have advanced four weeks in Western and Central Europe, and have been delayed up to two weeks in Eastern Europe. Western European spring starts earlier because of the intensive flow of warmer Atlantic air masses; the Eastern part of Europe has a different phenological rhythm and trends, that can be explained by the influence of the Siberian high. The highest rate of significant (p< 0.05) phenological change (−0.3 to −0.4 days per year) occurs in the Western Europe and Baltic Sea regions for early spring phases of hazel and colts‐foot. Spring phases of birch, apple and lilac, and summer phases, such as the flowering of linden, tend to occur earlier with an average rate of −0.1 to 0.3 days per year. Copyright © 2002 Royal Meteorological Society.
Assessing satellite‐derived start‐of‐season measures in the conterminous USA
Authors: Schwartz Mark D. , Reed Bradley C. , White Michael A.
Published: November 2002

National Oceanic and Atmospheric Administration (NOAA)‐series satellites, carrying advanced very high‐resolution radiometer (AVHRR) sensors, have allowed moderate resolution (1 km) measurements of the normalized difference vegetation index (NDVI) to be collected from the Earth's land surfaces for over 20 years. Across the conterminous USA, a readily accessible and decade‐long data set is now available to study many aspects of vegetation activity in this region. One feature, the onset of deciduous plant growth at the start of the spring season (SOS) is of special interest, as it appears to be crucial for accurate computation of several important biospheric processes, and a sensitive measure of the impacts of global change.

In this study, satellite‐derived SOS dates produced by the delayed moving average (DMA) and seasonal midpoint NDVI (SMN) methods, and modelled surface phenology (spring indices, SI) were compared at widespread deciduous forest and mixed woodland sites during 1990–93 and 1995–99, and these three measures were also matched to native species bud‐break data collected at the Harvard Forest (Massachusetts) over the same time period. The results show that both SOS methods are doing a modestly accurate job of tracking the general pattern of surface phenology, but highlight the temporal limitations of biweekly satellite data. Specifically, at deciduous forest sites: (1) SMN SOS dates are close in time to SI first bloom dates (average bias of +0.74 days), whereas DMA SOS dates are considerably earlier (average bias of −41.24 days) and also systematically earlier in late spring than in early spring; (2) SMN SOS tracks overall yearly trends in deciduous forests somewhat better than DMA SOS, but with larger average error (MAEs 8.64 days and 7.37 days respectively); and (3) error in both SOS techniques varies considerably by year. Copyright © 2002 Royal Meteorological Society.
The influence of temperature and climate change on the timing of pollen release in the Netherlands
Authors: van Vliet Arnold J. H. , Overeem Aart , De Groot Rudolf S. , Jacobs Adrie F. G. , Spieksma Frits T. M.
Published: November 2002

In the last decade it has become clear that the timing of many phenological processes, like the start of flowering and leaf unfolding in spring, have changed. The increase in temperature is believed to be the main cause. The earlier start of flowering will have consequences for the start of the pollen season, and thus for the start of the hay fever season. Millions of people world‐wide will therefore experience the impact of climate change in their daily lives during spring and summer. In this paper we analyse the relation between climate parameters, especially temperature, and the start of the pollen season in the western part of the Netherlands based on daily pollen counts of the Leiden University Medical Centre and temperature measurements from 1969 till 2000 by the Royal Netherlands Meteorological Institute in De Bilt. The results indicate that there is a strong correlation between temperature and start of the pollen season. An advance of the start of the pollen season of 3 to 22 days has been observed. The potential future changes in the start of the pollen season under climate change scenarios are also discussed. Copyright © 2002 Royal Meteorological Society.
Observed changes in seasons: an overview
Authors: Sparks T. H. , Menzel A.
Published: November 2002

Within the last decade the study of phenology has taken on a new legitimacy in the area of climate change research. A growing literature reveals that a change in the timing of natural events is occurring in a wide range of locations and affecting a wide range of species. Changes in spring have been those most commonly reported, with the emphasis on an advance in spring linked to an increase in temperature. Detection of change in autumn is hampered by a smaller pool of available data, events that are harder to define (such as leaf coloration), and various influencing environmental factors triggering autumnal phases. Despite this, the general pattern may be towards a delay in autumn. Plant, animal and abiotic responses, especially in spring, are quite similar. Thus, it would appear that winter is being squeezed at both ends, and this effect, of increasing the growing season, should become more pronounced in the face of predicted global warming. Copyright © 2002 Royal Meteorological Society.
Phenological studies in Australia: potential application in historical and future climate analysis
Authors: Keatley Marie R. , Fletcher Tim D. , Hudson Irene L. , Ades Peter K.
Published: November 2002

Phenological observations of eucalypts (Myrtaceae) were undertaken in four Australian states (New South Wales, Queensland, Victoria, and Western Australia) from the late 1920s until the early 1980s, by the respective State Forest Commissions. Unfortunately, few records have survived. For Victoria, surviving records encompass 42 forest districts, covering from less than 2 years to 42 years, and approximately 50 species.

This paper concentrates on the flowering of four competing species (Eucalyptus leucoxylon, E. microcarpa, E. polyanthemos, and E. tricarpa) over 23 years (1940–62) from Maryborough, Victoria, recorded on a monthly basis by one observer over the period. This study represents one of the first attempts to utilize Australian phenological data to detect responses to climate change.

There were no significant trends (P = 0.05) over time in the mean flowering commencement date. Forward stepwise regression found a significant relationship between temperature and flowering commencement in two species (E. leucoxylon: R2 = 0.42, P < 0.01; E. polyanthemos: R2 = 0.47, P = 0.02). Rainfall also had a significant influence on flowering commencement in E. tricarpa (R2 = 0.60, P < 0.01), E. leucoxylon (R2 = 0.43, P = 0.02) and E. polyanthemos (R2 = 0.24, P < 0.01). The combination of temperature and rainfall (with temperature exerting the greatest influence), however, was significant for all species and had the most explanatory power (ranging from R2 = 0.74 to 0.85, P < 0.01).

Overall, in response to predicted increases in temperature and summer rainfall, E. leucoxylon and E. tricarpa would commence flowering later. In E. polyanthemos and E. microcarpa, increased temperature and rainfall will result in an earlier onset of flowering. Copyright © 2002 Royal Meteorological Society.