bluuebunny/crossref_metadata_2025 huggingface dataset:
Forced Oscillations of a Damped Korteweg-de Vries Equation in a Quarter Plane
Authors: Bona Jerry L. , Sun S. M. , Zhang Bing-Yu
Published: July 2003

Laboratory experiments have shown that when nonlinear, dispersive waves are forced periodically from one end of an undisturbed stretch of the medium of propagation, the signal eventually becomes temporally periodic at each spatial point. It is our purpose here to establish this as a fact at least in the context of a damped Korteweg-de Vries equation. Thus, consideration is given to the initial-boundary-value problem [Formula: see text]

For this problem, it is shown that if the small amplitude, boundary forcing h is periodic of period T, say, then the solution u of (*) is eventually periodic of period T. More precisely, we show for each x > 0, that u(x, t + T) - u(x, t) converges to zero exponentially as t → ∞. Viewing (*) (without the initial condition) as an infinite dimensional dynamical system in the Hilbert space Hs(R+) for suitable values of s, we also demonstrate that for a given, small amplitude time-periodic boundary forcing, the system (*) admits a unique limit cycle, or forced oscillation (a solution of (*) without the initial condition that is exactly periodic of period T). Furthermore, we show that this limit cycle is globally exponentially stable. In other words, it comprises an exponentially stable attractor for the infinite-dimensional dynamical system described by (*).
The Prognostic Significance in Goodpasture’s Disease of Specificity, Titre and Affinity of Anti-Glomerular-Basement-Membrane Antibodies
Authors: Segelmark Mårten , Hellmark Thomas , Wieslander Jörgen
Published: August 2003

Background: The nephrotoxic potential of anti-glomerular-basement-membrane (GBM) antibodies has been demonstrated in numerous animal experiments. However, it is not known to what extent the properties of circulating anti-GBM antibodies in human disease reflect the severity of the disease and predict the outcome. Methods: Clinical data were collected for 79 Swedish patients for whom a positive result had previously been obtained with anti-GBM ELISA. In stored sera from the patients, we measured antibody concentration, specificity and affinity together with antineutrophil cytoplasmic antibodies and α1-antitrypsin phenotype. Results: Six months after diagnosis, 27 (34%) were dead, 32 (41%) were on dialysis treatment and only 20 (25%) were alive with a functioning native kidney. The best predictor for renal survival was renal function at diagnosis. In patients who were not dialysis dependent at diagnosis however, renal survival was associated with a lower concentration of anti-GBM antibodies, a lower proportion of antibodies specific for the immunodominant epitope and the histological severity of the renal lesion. The only factor that correlated with patient survival was age. Conclusions: Immunochemical properties of autoantibodies do not affect patient survival in anti-GBM disease but seem to be a factor in renal survival in patients detected before renal damage is too advanced.
Outcome after acute respiratory failure is more dependent on dysfunction in other vital organs than on the severity of the respiratory failure
Authors: Flaatten Hans , Gjerde Stig , Guttormsen Anne Berit , Haugen Oddbjørn , Høivik Tone , Onarheim Henning , Aardal Sidsel
Published: July 2003

Introduction

The incidence and outcome of acute respiratory failure (ARF) depend on dysfunction in other organs. As a result, reported mortality in patients with ARF is derived from a mixed group of patients with different degrees of multiorgan failure. The main goal of the present study was to investigate patient outcome in single organ ARF.

Patients and method

From 1 January 2000 to 1 July 2002, all adult patients (>16 years) in the intensive care unit (ICU) at Haukeland University Hospital were scored daily using the Sequential Organ Failure Assessment (SOFA) score for organ failure. ARF was defined by the SOFA criteria: ratio of arterial oxygen tension to fractional inspired oxygen, with a value < 26.6 kPa (200 mmHg) in more than one recording during the ICU stay (SOFA score 3 or 4). Patients with ARF alone and in combination with other severe organ failure (SOFA score 3 or 4) were included. Survival was recorded on discharge from the ICU, at hospital discharge and at 90 days after ICU discharge.

Results

During the period of study, 832 adult patients were treated and 529 (63.0%) had ARF. The ICU, hospital and 3-month mortality rates were lowest in single organ ARF (3.2, 14.7 and 21.8%, respectively), with increasing mortality with each additional organ failure. When ARF occurred with four or five additional organ failures, the 3-month mortality rate was 75%. No significant differences in mortality were found between early and late ARF.

Conclusion

The prognosis for ICU patients with single organ ARF is good, both in the short and long terms. The high overall mortality rate observed is caused by dysfunction in other organs.
Coherent development of dermomyotome and dermis from the entire mediolateral extent of the dorsal somite
Authors: Ben-Yair Raz , Kahane Nitza , Kalcheim Chaya
Published: August 2003

We have previously shown that overall growth of the myotome in the mediolateral direction occurs in a coherent and uniform pattern. We asked whether development of the dermomyotome and resultant dermis follow a similar pattern or are, alternatively, controlled by restricted pools of stem cells driving directional growth. To this end, we studied cellular events that govern dermomyotome development and the regional origin of dermis. Measurements of cell proliferation, nuclear density and cellular rearrangements revealed that the developing dermomyotome can be subdivided in the transverse plane into three distinct and dynamic regions: medial, central and lateral, rather than simply into epaxial and hypaxial domains. To understand how these temporally and spatially restricted changes affect overall dermomyotome growth, lineage tracing with CM-DiI was performed. A proportional pattern of growth was measured along the entire epithelium,suggesting that mediolateral growth of the dermomyotome is coherent. Hence,they contrast with a stem cell view suggesting focal and inversely oriented sources of growth restricted to the medial and lateral edges. Consistent with this uniform mediolateral growth, lineage tracing experiments showed that the dermomyotome-derived dermis originates from progenitors that reside along the medial as well as the lateral halves of somites, and whose contribution to dermis is regionally restricted. Taken together, our results support the view that all derivatives of the dorsal somite (dermomyotome, myotome and dermis)keep a direct topographical relationship with their epithelial ascendants.
Lipodystrophy in HIV-Infected Pediatric Patients Receiving Protease Inhibitors
Authors: Temple Mary E , Koranyi Katalin I , Nahata Milap C
Published: July 2003

BACKGROUND:

In adults with HIV infection, lipodystrophy syndrome may develop, characterized by peripheral wasting in the extremities, central obesity, hyperlipidemia, and insulin resistance. This syndrome occurs in HIV-positive pediatric patients who take protease inhibitors (PIs). However, the full characteristics of the syndrome in this population is not fully understood.

OBJECTIVE:

To evaluate the association between the use of PIs and the occurrence of lipodystrophy in HIV-infected children.

METHODS:

Pediatric patients attending an outpatient HIV clinic between 1994 and 2000 were prospectively enrolled. All patients were between 1 and 17 years of age and had received a PI for at least 1 month. The medical records were reviewed monthly for 3 months before PI therapy was started and then monthly for 36 months. At each evaluation, serum total cholesterol, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, triglycerides, and blood glucose concentrations were recorded, as well as physician-documented physical examination findings including subcutaneous fat in the arms, face, and legs, and abdominal girth. Baseline clinical and laboratory data were compared with follow-up data using a paired t-test.

RESULTS:

Twenty-one pediatric patients received a PI. Of these, 2 developed lipodystrophy, one at 15 months and one at 18 months after PI therapy was started. Neither child had had lipodystrophy before therapy. Twelve children who were taking ritonavir or nelfinavir, including 1 who developed lipodystrophy, developed abnormally high total cholesterol and triglyceride blood concentrations. All patients receiving indinavir also experienced a substantial increase in their triglyceride concentrations at follow-up evaluations, but no significant increases in total cholesterol occurred. Blood glucose concentrations were not significantly different between baseline and follow-up examinations in our patients.

CONCLUSIONS:

Lipodystrophy may occur in some HIV-infected children receiving PIs, and dyslipidemias may also develop in some patients taking these drugs.
Infliximab Treatment of Rheumatoid Arthritis and Crohn's Disease
Authors: Nahar Ibrahim K , Shojania Kam , Marra Carlo A , Alamgir Abul H , Anis Aslam H
Published: July 2003

OBJECTIVE:

To review the pharmacology, pharmacokinetics, efficacy, safety, and pharmacoeconomic impact of infliximab in the treatment of Crohn's disease (CD) and rheumatoid arthritis (RA).

DATA SOURCES:

MEDLINE and Pre-MEDLINE (1966–June 2002) and manufacturer prescribing literature were employed to find English-language articles on infliximab. Additional studies and abstracts were identified from the bibliographies of reviewed literature and conference proceedings.

STUDY SELECTION/DATA EXTRACTION:

All articles identified from data sources were evaluated, and all information deemed relevant was included in this review. Information regarding basic pharmacology was collected from studies in animals. Pharmacokinetic data were collected from human trials. Safety data were extracted from clinical trials and postmarketing surveillance. Priority was given to randomized, double-blind, placebo-controlled studies for the assessment of efficacy. All available economic evaluations were included.

DATA SYNTHESIS:

Infliximab is a new monoclonal antibody that appears to work by a unique mechanism: inhibiting the action of tumor necrosis factor-α (TNF-α). Infliximab is administered by intravenous infusion. In clinical trials in CD, infliximab significantly decreased the CD activity index compared with placebo in treatment-resistant disease and significantly reduced the number of draining fistulas in fistulizing disease. In RA, when infliximab was added to methotrexate (MTX), it resulted in a significant improvement in most disease outcome measures when compared with MTX plus placebo. Few major adverse effects were reported in the clinical trials; however, serious adverse events, including malignancy and demyelination, have been reported in postmarketing surveillance. Also, increased susceptibility to infections (including tuberculosis) has been reported.

CONCLUSIONS:

Infliximab is an effective new agent for the treatment of CD and RA. Its apparent unique mechanism of action makes infliximab an important addition to therapy. Caution should be exercised when considering infliximab for individuals who have chronic or recurrent infections, mild congestive heart failure (New York Heart Association [NYHA] class I/II), nervous system disorders, or live or have lived in an area endemic for histoplasmosis. Infliximab is contraindicated for patients with a clinically important, active infection, moderate to severe congestive heart failure (NYHA class III/IV), or an allergy to mouse proteins or any of the ingredients in infliximab. Further long-term efficacy, safety, and economic data on infliximab are required. Also, for the treatment of RA, the burden of administering infliximab (as a 2-hour supervised infusion) has to be considered when choosing among anti-TNF-α medication (as the other 2 approved agents, etanercept and adalimumab, can be self-administered by subcutaneous injection).
Fluoroquinolone AUIC Break Points and the Link to Bacterial Killing Rates
Authors: Schentag Jerome J , Meagher Alison K , Forrest Alan
Published: July 2003

OBJECTIVE:

To review in vitro and animal model studies with fluoroquinolones and the pharmacokinetic and pharmacodynamic relationships that are predictive of clinical and microbiologic outcomes and resistance. Data on fluoroquinolones are summarized and examine the premise that a single area under the inhibitory concentration–time curve (AUIC) target >125 may be used for all fluoroquinolones with concentration-dependent killing actions and against all target organisms.

DATA SOURCES:

Primary articles were identified by MEDLINE search (1966–February 2002) and through secondary sources.

STUDY SELECTION AND DATA EXTRACTION:

All of the articles identified from the data sources were evaluated, and all information deemed relevant was included.

DATA SYNTHESIS:

The fluoroquinolones exhibit concentration-dependent killing. This effect clearly depends on concentrations achieved, and outcomes depend on endpoints established by individual investigators. With AUIC values <60, the actions of fluoroquinolones are essentially bacteriostatic; any observed bacterial killing is the combined effect of low concentrations in relation to minimum inhibitory concentration and the action of host factors such as neutrophils and macrophages. AUIC values >100 but <250 yield bacterial killing at a slow rate, but usually by day 7 of treatment. AUICs >250 produce rapid killing, and bacterial eradication occurs within 24 hours. Disagreements regarding target endpoints are the expected consequences of comparing microbial and clinical outcomes across animal models, in vitro experiments, and humans when the endpoints are clearly not equivalent. Careful attention to time-related events, such as speed of bacterial killing, versus global endpoints, such as bacteriologic cure, allows optimal break points to be defined.

CONCLUSIONS:

Evidence from in vitro and animal models favors the use of AUIC values >250 for rapid bactericidal action, regardless of whether the organism is gram-negative or gram-positive.
Numerical simulation and PEPT measurements of a 3D conical helical‐blade mixer: A high potential solids mixer for solid‐state fermentation
Authors: Schutyser M. A. I. , Briels W. J. , Rinzema A. , Boom R. M.
Published: August 2003

Helical‐blade solids mixers have a large potential as bioreactors for solid‐state fermentation (SSF). Fundamental knowledge of the flow and mixing behavior is required for robust operation of these mixers. In this study predictions of a discrete particle model were compared to experiments with colored wheat grain particles and positron emission particle tracking (PEPT) measurements. In the discrete particle model individual movements of particles were calculated from interaction forces. It was concluded that the predicted overall flow behavior matched well with the PEPT measurements. Differences between the model predictions and the experiments with wheat grains were found to be due to the assumption that substrate particles were spherical, which was in the model. Model simulations and experiments with spherical green peas confirmed this. The mixing in the helical‐blade mixer could be attributed to (1) the transport of particles up and down in the interior of the mixer, and (2) dispersion or micro‐mixing of particles in the top region of the mixer. It appeared that the mixing rate scaled linearly with the rotation rate of the blade, although the average particle velocity did not scale proportionally. It may be that the flow behavior changes as a function of the rotation rate (e.g., changing thickness of the top region); further study is required to confirm this. To increase the mixing performance of the mixer, a larger blade or a change in the shape of the mixer (larger top surface/volume ratio) is recommended. © 2003 Wiley Periodicals, Inc. Biotechnol Bioeng 84: 29–39, 2003.
Transient self‐inhibition of the growth of Lactobacillus delbrueckii subsp. bulgaricus in a pH‐regulated fermentor
Authors: Mercade Myriam , Duperray Florence , Loubière Pascal
Published: August 2003

An industrial strain of Lactobacillus delbrueckii subsp. bulgaricus was grown in a synthetic medium on lactose as carbon substrate, in a pH‐regulated fermentor. Growth proceeded in two distinct phases separated by a transient stationary phase. Various experimental approaches were used to identify the cause of this growth arrest. Growth experiments in L. bulgaricus culture supernatant fluids collected at different cultivation times in fermentor, and supplemented or not with various nutritional solutions, enabled us to discard the possibility of a nutritional limitation. Tube cultures of L. bulgaricus in medium supplemented with various lactic acid concentrations showed a potential inhibition by this metabolic end product but confirmed that this inhibition was not responsible for the cessation of growth. It was concluded that at least one inhibitory compound was produced during the growth phase of the strain, and this compound disappeared from the medium in the transient stationary phase, enabling the growth to start again later in the culture. Indeed, the stoichiometric analysis of the culture showed, firstly, that unidentified carbon compounds were produced from lactose during growth, which were probably converted in lactic acid during the transient stationary phase and, secondly, that part of the amino acids consumed gave catabolic end products. Finally, bacteriocin‐like compounds were not considered to be responsible for this growth arrest. © 2003 Wiley Periodicals, Inc. Biotechnol Bioeng 84: 78–87, 2003.
Single‐nucleotide polymorphism analysis using fluorescence resonance energy transfer between DNA‐labeling fluorophore, fluorescein isothiocyanate, and DNA intercalator, POPO‐3, on bacterial magnetic particles
Authors: Nakayama Hideki , Arakaki Atsushi , Maruyama Kohei , Takeyama Haruko , Matsunaga Tadashi
Published: August 2003

To develop an analytical system for single‐nucleotide polymorphisms (SNPs), the fluorescence resonance energy transfer (FRET) technique was employed on a bacterial magnetic particle (BMP) surface. A combination of fluorescein isothiocyanate (FITC; excitation 490 nm/emission 520 nm) labeled at the 5′ end of DNA and an intercalating compound (POPO‐3, excitation 534 nm/emission 570 nm) was used to avoid the interference from light scattering caused by nanoparticles. After hybridization between target DNA immobilized onto BMPs and FITC‐labeled probes, fluorescence from POPO‐3, which was excited by the energy from the FITC, was detected. The major homozygous (ALDH2*1), heterozygous (ALDH2*1/*2), and minor homozygous (ALDH2*2) genotypes in the blood samples were discriminated by this method. The assay described herein allows for a simple and rapid SNP analysis using a fully automated system. © 2003 Wiley Periodicals, Inc. Biotechnol Bioeng 84: 96–102, 2003.
The invisible frontier. A multiple species model for the origin of behavioral modernity
Authors: D'Errico Francesco
Published: August 2003

Two contradictory theories of human cognitive evolution have been developed to model how, when, and among what hominid groups behavioral modernity emerged. The first model, which has long been the dominant paradigm, links these behavioral innovations to a cultural “revolution” by anatomically modern humans in Europe at around 40,000 years ago, coinciding with the first arrival of our species in this region.1–4 According to this model, the sudden and explosive character of this change is demonstrated by the appearance in the archeological record of previously unseen carvings, personal ornaments, musical instruments, depictions on cave walls, and new stone and bone technology. A variant of this model sees behavioral modernity resulting from a rapid biological change, a brain mutation producing no apparent change in skull anatomy, which occurred in Europe or, more probably, in Africa at ca. 50,000 years ago.56.
Modelling the water balance of a free‐draining lysimeter using the downward approach
Authors: Struthers Iain , Hinz Christoph , Sivapalan Murugesu , Deutschmann G. , Beese F. , Meissner R.
Published: August 2003

A 2600 m3 free‐draining lysimeter constructed in a Pinus sylvestris plantation forest in Colbitz, Germany, has been monitored daily since 1974, with the intent of improving the understanding the effect of afforestation upon groundwater recharge (drainage). The objective of this research was to employ a downward approach in the development of a conceptual water balance model applicable to the site. Observed annual and inter‐annual trends were successfully replicated by a simple capacitance model using a simplified representation of vegetation growth. An important limitation of the capacitance approach in simulating the timing of drainage at sub‐annual time scales was identified, which could not be overcome by adding complexity to the model basis. Given the a priori use of capacitance approaches for simulating drainage in many hydrological models, the findings of this study suggest that (a) these approaches are sufficient where the prediction of annual and inter‐annual drainage behaviour is the primary objective, and that (b) an alternative basis accounting for the time delay between precipitation inputs and drainage generation is required for modelling if the prediction of drainage at sub‐annual time scales is a priority. Copyright © 2003 John Wiley & Sons, Ltd.
Complete 1H and 13C NMR assignment for aryl diisoprenes
Authors: Zambrano Jorge L. , Rosales Viale
Published: August 2003

The characterization of four aryl diisoprenes was carried out by 1D‐ and 2D‐NMR methods, which permitted the assignment of the signals of all protons and all carbon atoms. Copyright © 2003 John Wiley & Sons, Ltd.
1H and 13C NMR spectral assignments of some natural abietane diterpenoids
Authors: Rodríguez Benjamín
Published: August 2003

An NMR study of 11 naturally occurring abietane diterpenoids is described. In addition to one‐dimensional NMR methods, including DPFGSE 1D‐NOE spectra, two‐dimensional shift‐correlated experiments [1H,1H COSY, 1H,13C‐gHSQC 1J(C,H) and 1H,13C‐gHMBC nJ(C,H) (n = 2 and 3)] were used for the complete and unambiguous 1H and 13C chemical shift assignments of these substances. Copyright © 2003 John Wiley & Sons, Ltd.
Dynamic 15N NMR studies of iron phosphine complexes containing coordinated dinitrogen
Authors: Field Leslie D. , Hazari Nilay , Li Hsiu Lin , Luck Ian J.
Published: August 2003

The 15N‐labelled iron dinitrogen complexes trans‐[FeH(N2)(PP)2]+[BPh4]− (PP = dppe, depe, dmpe) and cis‐[FeH(N2)(PP3)]+[BPh4]− were prepared in situ by exchange of unlabelled coordinated dinitrogen with 15N2. 15N NMR chemical shifts and coupling constants are reported. The 15N spectra exhibit separate signals for the metal‐bound and terminal nitrogen atoms of the coordinated N2. The 15N resonances display 15N, 15N coupling as well as 31P, 15N coupling and long‐range 15N, 1H coupling when there is a metal‐bound hydrido ligand. Exchange between free and coordinated dinitrogen was monitored by magnetization transfer between 15N‐labelled sites using an inversion–transfer–recovery experiment. Exchange between the metal‐bound and terminal nitrogen atoms of coordinated N2 was also monitored by magnetization transfer and this could proceed by N2 dissociation or by an intramolecular process. Copyright © 2003 John Wiley & Sons, Ltd.
Correlation between standing height, sitting height, and arm span as an index of pulmonary function in 6–10‐year‐old children
Authors: Torres Lídia A.G.M.M. , Martinez Francisco E. , Manço José C.
Published: August 2003

The present study evaluates the relationships of pulmonary volumes and flows and the anthropometric variables of standing height, sitting height, and arm span in 100 6–10‐year‐old children. To be included in the study, all children were required to be healthy and above the 3rd percentile of the curve of Tanner et al. (Arch Dis Child 1966;41:454–471; Arch Dis Child 1966;41:613–635) for height and weight. Standing height, sitting height, and arm span were measured according to standard protocol. The pulmonary function measurements were: tidal volume, minute respiratory volume, respiratory rate, expiratory reserve volume, inspiratory capacity, vital capacity, residual volume (RV), functional residual capacity, total lung capacity (TLC), forced vital capacity (FVC), forced expiratory volume in 1 sec of FVC (FEV1), forced expiratory flow measured between 25–75% of FVC, and FEV1/FVC and RV/TLC ratios. Simple linear regression best expressed the correlation between pulmonary function and the anthropometric variables. Significant correlations between anthropometric and pulmonary function measurements were observed, with FVC and FEV1 showing the highest and RV the lowest r2 values. There was a significant positive correlation between standing height and arm span according to linear regression and Bland‐Altman comparison (Bland and Altman, Lancet 1968;8:307–310). Our results suggest that when an accurate determination of standing height cannot be obtained, arm span could be used interchangeably, using the same regression equation. However, for patients with limb deformities, regression equations of pulmonary function measurements in relation to sitting height may be a better choice for estimating pulmonary function. Pediatr Pulmonol. 2003; 36:202–208. © 2003 Wiley‐Liss, Inc.
Migration to a western country increases asthma symptoms but not eosinophilic airway inflammation
Authors: Gibson Peter G. , Henry Richard L. , Shah Smita , Powell Heather , Wang He
Published: August 2003

The prevalence of asthma symptoms varies markedly throughout the world. However, the asthma mechanisms involved are not defined. Studying the effects of migration can help identify the reasons for this geographic variation. The aims of this study were to examine the prevalence of asthma symptoms, airway hyperresponsiveness (AHR), and induced sputum eosinophils in adolescents who migrate to Australia. The study was conducted in Sydney, Australia, where adolescent students completed a video symptom questionnaire, hypertonic saline challenge, sputum induction, and allergy skin testing. The 211 students had widely different cultural backgrounds, including Asian, South Pacific, Middle Eastern, European, and African countries. Among adolescents who were migrants to Australia, the prevalence of asthma symptoms was higher than that reported using a similar methodology in their country of origin. Asthma symptom prevalence was related to residence time in Australia. The prevalence of wheeze was 17.2% in recent arrivals, 20.5% in adolescents living in Australia for >2 years, and 36.3% in those living all their lifetime in Australia (P = 0.013). For every year of residence in Australia, there was an 11% increase in prevalence of current wheeze (odds ratio, 1.11;P = 0.02). This effect was not related to atopy, AHR, or eosinophilic airway inflammation. Sputum neutrophils were elevated in recent arrivals. In conclusion, adolescents who migrate to Australia report increased asthma symptoms, compared to their country of origin, and asthma symptoms are further increased for every additional year of residence in Australia. The development of wheeze after migration to Australia was independent of eosinophilic inflammation and consistent with noneosinophilic asthma mechanisms. Pediatr Pulmonol. 2003; 36:209–215. © 2003 Wiley‐Liss, Inc.
Changes in lung volume and work of breathing: A comparison of two variable‐flow nasal continuous positive airway pressure devices in very low birth weight infants
Authors: Courtney Sherry E. , Aghai Zubair H. , Saslow Judy G. , Pyon Kee H. , Habib Robert H.
Published: August 2003

Variable flow nasal continuous positive airway pressure (VF‐NCPAP) recruits lung volume more effectively and reduces work of breathing (WOB) compared to constant‐flow NCPAP (CF‐NCPAP) in very low birth weight (VLBW) infants. Because different VF‐NCPAP devices have somewhat different flow patterns, whether different VF‐NCPAP devices function similarly is unknown. We compared two VF‐NCPAP devices: the Infant Flow™ (EME, Ltd.) and the Arabella® (Hamilton Medical) to assess whether lung volume recruitment and WOB were similar in VLBW infants requiring NCPAP. Eighteen infants <1,500 g were studied on both NCPAP devices applied in random order. All infants required NCPAP for mild respiratory distress. Calibrated DC‐coupled respiratory inductance plethysmography (RIP) was used to assess lung volume changes. NCPAP was first increased to 8 cmH2O to allow comparable recruitment in all infants, and then was slowly decreased to 6, 4, and 0 cmH2O, with data collection at each level. Mean birth weight (±SD) was 1,107 ± 218 g, gestational age was 27.9 ± 2.0 weeks, weight at study was 1,092 ± 222 g, and age at study was 4.6 ± 4.3 days. There were no differences in lung volume recruitment overall or at any NCPAP level (P = 0.943). No differences were found in either inspiratory WOB (P = 0.468) or in resistive WOB (P = 0.610) between devices. Compliance, tidal volume, respiratory rate, and minute ventilation were also similar. Despite differences in flow characteristics between the two VF‐NCPAP devices we studied, lung volume recruitment and WOB were similar. Pediatr Pulmonol. 2003; 36:248–252. © 2003 Wiley‐Liss, Inc.
How well can we predict native contacts in proteins based on decoy structures and their energies?
Authors: Zhu Jiang , Zhu Qianqian , Shi Yunyu , Liu Haiyan
Published: August 2003

One strategy for ab initio protein structure prediction is to generate a large number of possible structures (decoys) and select the most fitting ones based on a scoring or free energy function. The conformational space of a protein is huge, and chances are rare that any heuristically generated structure will directly fall in the neighborhood of the native structure. It is desirable that, instead of being thrown away, the unfitting decoy structures can provide insights into native structures so prediction can be made progressively. First, we demonstrate that a recently parameterized physics‐based effective free energy function based on the GROMOS96 force field and a generalized Born/surface area solvent model is, as several other physics‐based and knowledge‐based models, capable of distinguishing native structures from decoy structures for a number of widely used decoy databases. Second, we observe a substantial increase in correlations of the effective free energies with the degree of similarity between the decoys and the native structure, if the similarity is measured by the content of native inter‐residue contacts in a decoy structure rather than its root‐mean‐square deviation from the native structure. Finally, we investigate the possibility of predicting native contacts based on the frequency of occurrence of contacts in decoy structures. For most proteins contained in the decoy databases, a meaningful amount of native contacts can be predicted based on plain frequencies of occurrence at a relatively high level of accuracy. Relative to using plain frequencies, overwhelming improvements in sensitivity of the predictions are observed for the 4_state_reduced decoy sets by applying energy‐dependent weighting of decoy structures in determining the frequency. There, approximately 80% native contacts can be predicted at an accuracy of approximately 80% using energy‐weighted frequencies. The sensitivity of the plain frequency approach is much lower (20% to 40%). Such improvements are, however, not observed for the other decoy databases. The rationalization and implications of the results are discussed. Proteins 2003;52:598–608. © 2003 Wiley‐Liss, Inc.
Structure, evolution, and inhibitor interaction of S‐adenosyl‐L‐homocysteine hydrolase from Plasmodium falciparum
Authors: Bujnicki Janusz M. , Prigge Sean T. , Caridha Diana , Chiang Peter K.
Published: August 2003

S‐adenosylhomocysteine hydrolase (SAHH) is a key regulator of S‐adenosylmethionine–dependent methylation reactions and an interesting pharmacologic target. We cloned the SAHH gene from Plasmodium falciparum (PfSAHH), with an amino acid sequence agreeing with that of the PlasmoDB genomic database. Even though the expressed recombinant enzyme, PfSAHH, could use 3‐deaza‐adenosine (DZA) as an alternative substrate in contrast to the human SAHH, it has a unique inability to substitute 3‐deaza‐(±)aristeromycin (DZAri) for adenosine. Among the analogs of DZA, including neplanocin A, DZAri was the most potent inhibitor of the PfSAHH enzyme activity, with a Ki of about 150 nM, whether Ado or DZA was used as a substrate. When the same DZA analogs were tested for their antimalarial activity, they also inhibited the in vitro growth of P. falciparum parasites potently. Homology‐modeling analysis revealed that a single substitution (Thr60‐Cys59) between the human and malarial PfSAHH, in an otherwise similar SAH‐binding pocket, might account for the differential interactions with the nucleoside analogs. This subtle difference in the active site may be exploited in the development of novel drugs that selectively inhibit PfSAHH. We performed a comprehensive phylogenetic analysis of the SAHH superfamily and inferred that SAHH evolved in the common ancestor of Archaea and Eukaryota, and was subsequently horizontally transferred to Bacteria. Additionally, an analysis of the unusual and uncharacterized AHCYL1 family of the SAHH paralogs extant only in animals reveals striking divergence of its SAH‐binding pocket and the loss of key conserved residues, thus suggesting an evolution of novel function(s). Proteins 2003;52:624–632. © 2003 Wiley‐Liss, Inc.
The Arabidopsis MEI1 gene encodes a protein with five BRCT domains that is involved in meiosis‐specific DNA repair events independent of SPO11‐induced DSBs
Authors: Mathilde Grelon , Ghislaine Gendrot , Daniel Vezon , Georges Pelletier
Published: August 2003

Arabidopsis thaliana MEI1 was first described as a gene involved in male meiosis, encoding a short protein showing homology with a human acrosin–trypsin inhibitor. We have isolated a new allele of mei1, and shown that in both mutants male and female meiosis are affected. In both reproductive pathways, meiosis proceeds while chromosomes become fragmented, resulting in aberrant meiotic products and in a strongly reduced fertility. We have shown that the gene mutated in mei1 mutants actually encodes a protein of 972 amino acids that contains five BRCA1 C‐terminus (BRCT) domains and is similar to proteins involved in the response to DNA damage and replication blocks in eukaryotes. During meiosis, recombination is initiated by the formation of DNA double strand breaks (DSBs) induced by the protein SPO11. We analysed meiotic chromosome behaviour of the mei1 mutant in a spo11 mutant background and proved that the meiotic fragmentation observed in mei1 mutants was not the consequence of defects in the repair of meiotic DSBs induced by SPO11. We also analysed the effect of mei1 on the mitotic cell cycle but could not detect any sensitivity of mei1 seedlings to DNA‐damaging agents like γ‐rays or UV. Therefore, MEI1 is a BRCT‐domain‐containing protein that could be specific to the meiotic cell cycle and that plays a crucial role in some DNA repair events independent of SPO11 DSB recombination repair.
Why green fluorescent fusion proteins have not been observed in the vacuoles of higher plants
Authors: Tamura Kentaro , Shimada Tomoo , Ono Eiichiro , Tanaka Yoshikazu , Nagatani Akira , Higashi Sho‐ich , Watanabe Masakatsu , Nishimura Mikio , Hara‐Nishimura Ikuko
Published: August 2003

Green fluorescent protein (GFP) makes it possible for organelles and protein transport pathways to be visualized in living cells. However, GFP fluorescence has not yet been observed in the vacuoles of any organs of higher plants. We found that the fluorescence of a vacuole‐targeted GFP was stably observed in the vacuoles of transgenic Arabidopsis plants under dark conditions, and that the fluorescence rapidly disappeared under light conditions. The vacuolar GFP was rapidly degraded within 1 h in the light, especially blue light. An inhibitor of vacuolar type H+‐ATPase, concanamycin A, and an inhibitor of papain‐type cysteine proteinase, E‐64d, abolished both the light‐dependent disappearance of GFP fluorescence and GFP degradation in the vacuoles. An in vitro assay showed that bacterially expressed GFP was degraded by extracts of Arabidopsis cultured‐cell protoplasts at an acidic pH in the light. These results suggest that blue light induced a conformational change in GFP, and the resulting GFP in the vacuole was easily degraded by vacuolar papain‐type cysteine proteinase(s) under the acidic pH. The light‐dependent degradation accounts for the failure to observe GFP fluorescence in the vacuoles of plant organs. Our results show that stable GFP‐fluoresced vacuoles are achieved by transferring the plants from the light into the dark before inspection with a fluorescent microscope. This might eliminate a large hurdle in studies of the vacuolar‐targeting machinery and the organ‐ and stage‐specific differentiation of endomembrane systems in plants.
ILR2, a novel gene regulating IAA conjugate sensitivity and metal transport in Arabidopsis thaliana
Authors: Magidin Mónica , Pittman Jon K. , Hirschi Kendal D. , Bartel Bonnie
Published: August 2003

Plants can regulate levels of the auxin indole‐3‐acetic acid (IAA) by conjugation to amino acids or sugars, and subsequent hydrolysis of these conjugates to release active IAA. These less active auxin conjugates constitute the majority of IAA in plants. We isolated the Arabidopsis ilr2‐1 mutant as a recessive IAA‐leucine resistant mutant that retains wild‐type sensitivity to free IAA. ilr2‐1 is also defective in lateral root formation and primary root elongation. In addition, ilr2‐1 is resistant to manganese‐ and cobalt‐mediated inhibition of root elongation, and microsomal preparations from the ilr2‐1 mutant exhibit enhanced ATP‐dependent manganese transport. We used a map‐based positional approach to clone the ILR2 gene, which encodes a novel protein with no predicted membrane‐spanning domains that is polymorphic among Arabidopsis accessions. Our results demonstrate that ILR2 modulates a metal transporter, providing a novel link between auxin conjugate metabolism and metal homeostasis.
Control of pollen tube growth: role of ion gradients and fluxes
Authors: Holdaway‐Clarke Terena L. , Hepler Peter K.
Published: August 2003

Pollen tube growth attracts our attention as a model system for studying cell elongation in plants. The process is fast, it is confined to the tip of the tube, and it is crucial for sexual reproduction in plants. In the enclosed review we focus on the control of pollen tube growth, giving special attention to the role of ions, especially calcium and protons. During the last decade technical advances have made it possible to detect localized intracellular gradients, and extracellular fluxes of calcium and protons in the apical domain. Other ions, notably potassium and chloride, are also receiving attention. An important development has been the realization that pollen tube growth oscillates in rate; in addition, the ion gradients and fluxes oscillate in magnitude. Although all the ionic oscillations show the same period as that of the growth rate, with the exception of extracellular chloride efflux, they are not in phase with growth. Considerable effort is devoted to the elucidation of these different phase relationships, with the view that a hierarchical order may provide clues about those events that are primary vs. secondary in growth control. Attention is also given to the targets for the ions, for example, the secretory system, the cytoskeleton, the cell wall, in an attempt to provide a global understanding of pollen tube growth.ContentsSummary539I.Introduction540II.Ion gradients and flux patterns541III.Oscillations544IV.The need for a Ca2+store547V.Intracellular targets for Ion activity549VI.Extracellular targets for ions: the cell wall552VII.Ions in navigation554VIII.Role of ions in self‐incompatibility555IX.The plasma membrane; site of global coordination and control556X.A model for pollen tube growth557IX.Conclusions558Acknowledgements559References559
Bacterial ceramides and sphingophospholipids induce apoptosis of human leukaemic cells
Authors: Minamino Miki , Sakaguchi Ikuyo , Naka Takashi , Ikeda Norikazu , Kato Yoshiko , Tomiyasu Ikuko , Yano Ikuya , Kobayashi Kazuo
Published: August 2003

The genusSphingobacterium, whose members are Gram-negative non-fermentative rods, possesses ceramides and related sphingophospholipids (SPLs) with isoheptadecasphinganine and 2-hydroxy or non-hydroxy isopentadecanoic acid. This paper reports evidence that ceramides isolated fromSphingobacterium spiritivorumATCC 33861 induce endonucleolytic DNA cleavage in human myeloid leukaemia HL-60 cellsin vitro, which is the primary characteristic biochemical marker for apoptosis or programmed cell death. Ceramides and SPLs also induced DNA fragmentation and caspase-3 activation, followed by changes in morphology, such as alterations in the size of nuclei and cells, and cell cycle shortening. Apoptotic activity correlated with the ceramide structure. Ceramide with a 2-hydroxy fatty acid showed stronger apoptotic activity than ceramide with a non-hydroxy fatty acid. Furthermore, the major five SPLs (ceramide phosphorylethanolamine-1 and -2, ceramide phosphorylinositol-1 and -2, and ceramide phosphorylmannose-1) showed apoptosis-inducing activity in HL-60 cells, indicating that the ceramide moiety of the SPLs plays a crucial role as the intracellular second messenger but that their hydrophilicity is less important in this regard. The hydrophilic part of SPLs may play a role in other cellular response systems. The involvement of Fas antigen was implicated in the apoptotic event since Fas antigen expression was observed after 3 or 4 h stimulation of HL-60 cells with bacterial ceramides. However, a time-course study for caspase-3 activation indicated maximal activity at 1 h after stimulation with bacterial ceramides, suggesting that two (or possibly more) mechanisms of signal transduction, Fas-dependent and Fas-independent, may be involved. Fas antigen expression and caspase-3 activation by five kinds of SPLs were observed after 3 or 4 h. These results indicate that there is a difference in the response of HL-60 cells to bacterial ceramides and SPLs.
Dynamic FtsZ polymerization is sensitive to the GTP to GDP ratio and can be maintained at steady state using a GTP-regeneration system
Authors: Small Elaine , Addinall Stephen G.
Published: August 2003

In vitro polymerization of the essential bacterial cell division protein FtsZ, in the presence of GTP, is rapid and transient due to its efficient binding and hydrolysis of GTP. In contrast, the in vivo polymeric FtsZ structure which drives cell division – the Z-ring – is present in cells for extended periods of time whilst undergoing constant turnover of FtsZ. It is demonstrated that dynamic polymerization of Escherichia coli FtsZ in vitro is sensitive to the ratio of GTP to GDP concentration. Increase of GDP concentration in the presence of a constant GTP concentration reduces both the duration of FtsZ polymerization and the initial light-scattering maximum which occurs upon addition of GTP. It is also demonstrated that by use of a GTP-regeneration system, polymers of FtsZ can be maintained in a steady state for up to 85 min, while preserving their dynamic properties. The authors therefore present the use of a GTP-regeneration system for FtsZ polymerization as an assay more representative of the in vivo situation, where FtsZ polymers are subject to a constant, relatively high GTP to GDP ratio.
Physiological role of S-formylglutathione hydrolase in C1 metabolism of the methylotrophic yeast Candida boidinii
Authors: Yurimoto Hiroya , Lee Bumjun , Yano Taisuke , Sakai Yasuyoshi , Kato Nobuo
Published: August 2003

The methylotrophic yeastCandida boidiniiexhibitsS-formylglutathione hydrolase activity (FGH, EC 3.1.2.12), which is involved in the glutathione-dependent formaldehyde oxidation pathway during growth on methanol as the sole carbon source. The structural gene,FGH1, was cloned fromC. boidinii, and its predicted amino acid sequence showed more than 60 % similarity to those of FGHs fromParacoccus denitrificansandSaccharomyces cerevisiae, and human esterase D. FGH fromC. boidiniicontained a C-terminal tripeptide, SKL, which is a type I peroxisome-targeting signal, and a bimodal distribution of FGH between peroxisomes and the cytosol was demonstrated. TheFGH1gene was disrupted in theC. boidiniigenome by one-step gene disruption. Thefgh1Δ strain was still able to grow on methanol as a carbon source under methanol-limited chemostat conditions with low dilution rates (D<0·05 h−1), conditions under which a strain with disruption of the gene for formaldehyde dehydrogenase (another enzyme involved in the formaldehyde oxidation pathway) could not survive. These results suggested that FGH is not essential but necessary for optimal growth on methanol. This is believed to be the first report of detailed analyses of theFGH1gene in a methylotrophic yeast strain.
Overexpression of the polynucleotide phosphorylase gene (pnp) of Streptomyces antibioticus affects mRNA stability and poly(A) tail length but not ppGpp levels
Authors: Bralley Patricia , Jones George H.
Published: August 2003

The pnp gene, encoding the enzyme polynucleotide phosphorylase (PNPase), was overexpressed in the actinomycin producer Streptomyces antibioticus. Integration of pIJ8600, bearing the thiostrepton-inducible tipA promoter, and its derivatives containing pnp into the S. antibioticus chromosome dramatically increased the growth rate of the resulting strains as compared with the parent strain. Thiostrepton induction of a strain containing pJSE340, bearing pnp with a 5′-flanking region containing an endogenous promoter, led to a 2·5–3 fold increase in PNPase activity levels, compared with controls. Induction of a strain containing pJSE343, with only the pnp ORF and some 3′-flanking sequence, led to lower levels of PNPase activity and a different pattern of pnp expression compared with pJSE340. Induction of pnp from pJSE340 resulted in a decrease in the chemical half-life of bulk mRNA and a decrease in poly(A) tail length as compared to RNAs from controls. Actinomycin production decreased in strains overexpressing pnp as compared with controls but it was not possible to attribute this decrease specifically to the increase in PNPase levels. Overexpression of pnp had no effect on ppGpp levels in the relevant strains. It was observed that the 3′-tails associated with RNAs from S. antibioticus are heteropolymeric. The authors argue that those tails are synthesized by PNPase rather than by a poly(A) polymerase similar to that found in Escherichia coli and that PNPase may be the sole RNA 3′-polynucleotide polymerase in streptomycetes.