bluuebunny/crossref_metadata_2025 huggingface dataset:
Developmental regulation of the Hox genes during axial morphogenesis in the mouse
Authors: Deschamps Jacqueline , van Nes Johan
Published: June 2005

The Hox genes confer positional information to the axial and paraxial tissues as they emerge gradually from the posterior aspect of the vertebrate embryo. Hox genes are sequentially activated in time and space, in a way that reflects their organisation into clusters in the genome. Although this co-linearity of expression of the Hox genes has been conserved during evolution, it is a phenomenon that is still not understood at the molecular level. This review aims to bring together recent findings that have advanced our understanding of the regulation of the Hox genes during mouse embryonic development. In particular, we highlight the integration of these transducers of anteroposterior positional information into the genetic network that drives tissue generation and patterning during axial elongation.
Spatial re-organisation of cortical microtubules in vivo during polarisation and asymmetric division ofFucuszygotes
Authors: Corellou Florence , Coelho Susana M. B. , Bouget François-Yves , Brownlee Colin
Published: June 2005

Fucus zygotes polarise and germinate a rhizoid before their first asymmetrical division. The role of microtubules (MTs) in orienting the first division plane has been extensively studied by immunofluorescence approaches. In the present study, the re-organisation of MT arrays during the development of Fucus zygotes and embryos was followed in vivo after microinjection of fluorescent tubulin. A dynamic cortical MT array that shows dramatic reorganization during zygote polarization was detected for the first time. Randomly distributed cortical MTs were redistributed to the presumptive rhizoid site by the time of polarisation and well before rhizoid germination. The cortical MT re-organisation occurs independently of centrosome separation and nucleation. By the time of mitosis the cortical array depolymerised to cortical foci in regions from which it also reformed following mitosis, suggesting that it is nucleated from cortical sites. We confirm previous indications from immunodetection studies that centrosomal alignment and nuclear rotation occur via MT connexions to stabilised cortical sites and that definitive alignment is post-metaphasic. Finally, we show that cortical MTs align parallel to the growth axis during rhizoid tip growth and our results suggest that they may be involved in regulating rhizoid growth by shaping the rhizoid and containing turgor pressure
A phenylalanine-based folding determinant in intestinal sucrase-isomaltase that functions in the context of a quality control mechanism beyond the endoplasmic reticulum
Authors: Pröpsting Marcus J. , Kanapin Heike , Jacob Ralf , Naim Hassan Y.
Published: June 2005

Phenotype II of congenital sucrase-isomaltase deficiency in man is characterized by a retention of the brush border protein sucrase-isomaltase (SI) in the ER/cis-Golgi intermediate compartment (ERGIC) and the cis-Golgi. The transport block is due to the substitution of a glutamine by a proline at amino acid residue 1098 that generates a temperature-sensitive mutant enzyme, SIQ1098P, the transport of which is regulated by several cycles of anterograde and retrograde transport between the ER and the cis-Golgi (Propsting, M. J., Jacob, R. and Naim, H. Y. (2003). J. Biol. Chem. 278, 16310-16314). A quality control beyond the ER has been proposed that implicates a retention signal or a folding determinant elicited by the Q1098P mutation. We have used alanine-scanning mutagenesis to screen upstream and downstream regions flanking Q1098 and identified a putative motif, F1093-x-F1095-x-x-x-F1099 that is likely to be implicated in sensing the folding and subsequent trafficking of SI from the ER to the Golgi. The characteristics of this motif are three phenylalanine residues that upon substitution by alanine generate the temperature-sensitive SIQ1098P phenotype. This mutant protein undergoes transport arrest in the ERGIC and cis-Golgi compartments and acquires correct folding and functional activity at reduced temperatures as a consequence of cycles of anterograde and retrograde transport between the ER and cis-Golgi. Other amino acid residues in this motif are not significant in the context of phenotype II. We propose that the phenylalanine cluster is required for shielding a folding determinant in the extracellular domain of SI; substitution of a Q by a P at residue 1098 of sucrase disrupts this determinant and elicits retention of SIQ1098P in ERGIC and cis-Golgi in phenotype II of CSID.
RhoB regulates endosome transport by promoting actin assembly on endosomal membranes through Dia1
Authors: Fernandez-Borja Mar , Janssen Lennert , Verwoerd Desiree , Hordijk Peter , Neefjes Jacques
Published: June 2005

Rho GTPases are crucial regulators of the actin cytoskeleton and they play a role in the control of membrane trafficking. In contrast to the close family members RhoA and RhoC, RhoB localises to endosomes and delays epidermal growth factor receptor traffic. Here, we show that activated RhoB induces the peripheral distribution of endosomes, which align along subcortical actin stress fibres and are surrounded by an actin coat. The Diaphanous-related formin, Dia1, is recruited to endosomes by activated RhoB. Dia1 is required for the formation of the actin coat around endosomes downstream of RhoB, connecting membrane trafficking with the regulation of actin dynamics.
Two novel proteins recruited by synaptonemal complex protein 1 (SYCP1) are at the centre of meiosis
Authors: Costa Yael , Speed Robert , Öllinger Rupert , Alsheimer Manfred , Semple Colin A. , Gautier Philippe , Maratou Klio , Novak Ivana , Höög Christer , Benavente Ricardo , Cooke Howard J.
Published: June 2005

Completion of meiosis in mammals depends on the formation of the synaptonemal complex, a tripartite structure that physically links homologous chromosomes during prophase I. Several components of the synaptonemal complex are known, including constituents of the cohesin core, the axial/lateral element and the transverse filaments. No protein has previously been identified as an exclusive component of the central element. Mutations in some synaptonemal-complex proteins results in impaired meiosis. In humans, cases of male infertility have been associated with failure to build the synaptonemal complex. To search for new components of the meiotic machinery, we have used data from microarray expression profiling and found two proteins localising solely to the central element of the mammalian synaptonemal complex. These new proteins, SYCE1 and CESC1, interact with the transverse filament protein SYCP1, and their localisation to the central element appears to depend on recruitment by SYCP1. This suggests a role for SYCE1 and CESC1 in synaptonemal-complex assembly, and perhaps also stability and recombination.
Three-dimensional polarization sensitizes hepatocytes to Fas/CD95 apoptotic signalling
Authors: Haouzi Delphine , Baghdiguian Stephen , Granier Guillaume , Travo Pierre , Mangeat Paul , Hibner Urszula
Published: June 2005

Maintenance of epithelial cell shape and polarity determines many vital cell functions, including the appropriate response to external stimuli. Murine hepatocytes cultured in a three-dimensional Matrigel matrix formed highly polarized organoids characterized by specific localization of an ERM (ezrin/radixin/moesin) protein, radixin, at microvillus-lined membrane domains. These apical domains surrounded a lumen and were bordered by tight junctions. The hepatocyte organoids were functional as judged by the high level of albumin secretion and accumulation of bilirubin. Stimulation of the Fas/CD95 death receptor, which is highly hepatotoxic in vivo, was a strong inducer of apoptosis in the polarized organoids. This was in sharp contrast to the monolayer hepatocyte cultures, which were protected from death by exacerbated NF-κB signalling following engagement of the death receptors. Thus, hepatocytes in polarized, functional organoids modulate an intracellular signal transduction pathway, allowing the recapitulation of their physiological response to an apoptotic stimulus.
Urokinase-induced activation of the gp130/Tyk2/Stat3 pathway mediates a pro-inflammatory effect in human mesangial cells via expression of the anaphylatoxin C5a receptor
Authors: Shushakova Nelli , Tkachuk Natalia , Dangers Marc , Tkachuk Sergey , Park Joon-Keun , Hashimoto Koji , Haller Hermann , Dumler Inna
Published: June 2005

Glomerular mesangial cells (MCs) are central to the pathogenesis of progressive glomeruli-associated renal diseases. However, molecular mechanisms underlying changes in MC functions still remain poorly understood. Here, we show that in MCs, the urokinase-type plasminogen activator (uPA) induces, via its specific receptor (uPAR, CD87), upregulated expression of the complement anaphylatoxin C5a receptor (C5aR, CD88), and modulates C5a-dependent functional responses. This effect is mediated via the interaction of the uPA-specific receptor (uPAR, CD87) and gp130, a signal transducing subunit of the receptor complexes for the IL-6 cytokine family. The Janus kinase Tyk2 and the transcription factor Stat3 serve as downstream components in the signaling cascade resulting in upregulation of C5aR expression. In vivo, expression of C5aR and uPAR was increased in the mesangium of wild-type mice in a lipopolysaccharide (LPS)-induced model of inflammation, whereas in uPAR–/– animals C5aR expression remained unchanged. This is the first demonstration in vitro and in vivo that uPA acts in MCs as a modulator of immune responses via control of immune-competent receptors. The data suggest a novel role for uPA/uPAR in glomeruli-associated renal failure via a signaling cross-talk between the fibrinolytic and immune systems.
Molecular stop signs: regulation of cell-cycle arrest by C/EBP transcription factors
Authors: Johnson Peter F.
Published: June 2005

The CCAAT/enhancer-binding protein (C/EBP) family of transcription factors plays an important role in controlling cell proliferation and differentiation. C/EBPα is a particularly potent regulator of cell-cycle exit and is induced in terminally differentiating adipocytes and myeloid cells, where it also activates differentiation-specific genes. The growth-inhibiting activity of C/EBPα suppresses tumorigenesis in myeloid cells and possibly other tissues. In addition, recent work has identified C/EBPα as a component of the p53-regulated growth arrest response elicited by DNA damage in epidermal keratinocytes. Several studies have explored the mechanism by which C/EBPα blocks cell-cycle progression at the G1-S boundary, and several models have been proposed but no universally accepted mechanism has emerged. Controversial issues include whether C/EBPα acts through an `off-DNA' mechanism to inhibit cyclin-dependent kinases, and whether and how it functions with the RB-E2F system to repress transcription of S-phase genes. Other C/EBP-family members have also been implicated in positive and negative control of cell proliferation, and the mechanisms underlying their growth-regulatory activities are beginning to be elucidated.
Complementary therapies for the treatment of HIV: in search of the evidence
Authors: Mills Edward , Wu Ping , Ernst Edzard
Published: June 2005

The use of complementary and alternative medicine (CAM) is widespread. Yet, little is known about the evidence supporting its use in HIV/AIDS. We conducted a systematic review of randomized clinical trials assessing the effectiveness of complementary therapies for HIV and HIV-related symptoms. Comprehensive literature searches were performed of seven electronic databases. Data were abstracted independently by two reviewers. Thirty trials met our predefined inclusion/exclusion criteria: 18 trials were of stress management; five of Natural Health Products; four of massage/therapeutic touch; one of acupuncture; two of homeopathy. The trials were published between 1989 and 2003. Most trials were small and of limited methodological rigour. The results suggest that stress management may prove to be an effective way to increase the quality of life. For all other treatments, data are insufficient for demonstrating effectiveness. Despite the widespread use of CAM by people living with HIV/AIDS, the effectiveness of these therapies has not been established. Vis à vis CAM's popularity, the paucity of clinical trials and their low methodological quality are concerning.
Staphylococcus sciuri: an unusual cause of pelvic inflammatory disease
Authors: Stepanović S , Ježek P , Dakić I , Vuković D , Seifert L
Published: June 2005

We present the case of polymicrobial pelvic inflammatory disease (PID) that involved Staphylococcus sciuri, S. epidermidis, and Streptococcus agalactiae. In order to determine the frequency of S. sciuri isolation from the female lower genital tract, 3415 vaginal samples were analysed during the one-year study period. S. sciuri was isolated from three (0.09%) samples. In all the three cases, S. sciuri was obtained in mixed culture from outpatients without symptoms of infection. While the origin of S. sciuri in the female genital tract remains to be elucidated, the present study showed that this bacterium may colonize vagina and, moreover, may be involved in the pathogenesis of an infection as serious as PID. The low rate of isolation we established, however, indicates infrequent and, most probably, transient colonization of the female genital tract by S. sciuri.
Verification of clinical samples, positive in AMPLICOR Neisseria gonorrhoeae polymerase chain reaction, by 16S rRNA and gyrA compared with culture
Authors: Airell Åsa , Lindbäck Emma , Ataker Ferda , Pörnull Kirsti Jalakas , Wretlind Bengt
Published: June 2005

We compared 956 samples for AMPLICOR Neisseria gonorrhoeae polymerase chain reaction (PCR) (Roche) with species verification using the 16S rRNA gene to verification using gyrA gene. Control was the culture method. The gyrA verification uses pyrosequencing of the quinolone resistance-determining region of gyrA. Of 52 samples with optical density ≥0.2 in PCR, 27 were negative in culture, two samples from pharynx were false negative in culture and four samples from pharynx were false positives in verification with 16S rRNA. Twenty-five samples showed growth of gonococci, 18 of the corresponding PCR samples were verified by both methods; three urine samples were positive only in gyrA ; and one pharynx specimen was positive only in 16S rRNA. Three samples were lost. We conclude that AMPLICOR N. gonorrhoeae PCR with verification in gyrA gene can be considered as a diagnostic tool in populations with low prevalence of gonorrhoea and that pharynx specimens should not be analysed by PCR.
Molecular testing (strand displacement assay) for identification of urethral gonorrhoea in men: can it replace culture as the gold standard?
Authors: Wheeler H L , Skinner C J , Khunda A , Aitken C , Perpanthan D , Staite E
Published: June 2005

The objective was to evaluate the performance of Becton Dickinson's BD Probe TecTM (BDPT) strand displacement amplification (SDA) test for the detection of Neisseria gonorrhoeae on urethral specimens from men with urethritis compared with conventional culture and to show that SDA improves the diagnostic yield of gonorrhoea infections (GC). Anonymized retrospective testing of stored urethral swab samples from men attending genitourinary services in East London was performed using SDA. The prevalence of GC culture positive infections in this sample was 20/152 (13%). The sensitivity, specificity, positive predictive value and negative predictive value for the BDPT-SDA system compared with culture were 100%, 95%, 77% and 100%, respectively. In this study population, the BDPT-SDA assay was a highly sensitive and specific test for the diagnosis of N. gonorrhoeae from urethral swabs in men. Therefore, SDA can be used to complement culture in the diagnosis of N. gonorrhoeae infection. No ethics committee approval was obtained as all samples were anonymized.
Selective Serotonin-Reuptake Inhibitors in the Treatment of Premature Ejaculation
Authors: Moreland Amanda J , Makela Eugene H
Published: June 2005

OBJECTIVE

To review the use of selective serotonin-reuptake inhibitors (SSRIs) in the treatment of premature ejaculation.

DATA SOURCES

Articles were retrieved through a MEDLINE search (1966–January 2004). Search terms used to identify articles included serotonin uptake inhibitors, premature ejaculation, rapid ejaculation, and sexual behavior, as well as the generic names of currently available SSRIs: fluoxetine, fluvoxamine, paroxetine, sertraline, citalopram, and escitalopram. The literature search was limited to articles published in the English language containing human subjects.

STUDY SELECTION AND DATA EXTRACTION

Articles obtained through the literature search were evaluated, and randomized controlled trials were included in this review. Information from noncontrolled trials or case reports was considered for inclusion if it contributed to the completeness of this review and if it was the highest level of evidence available.

DATA SYNTHESIS

Premature ejaculation is a commonly reported sexual difficulty. Delayed ejaculation is a widely reported sexual adverse effect of SSRIs. In some men exhibiting premature ejaculation, the ability of the SSRIs to delay ejaculation has been therapeutic. Trials evaluating the ejaculation-delaying ability of SSRIs demonstrated that paroxetine, fluoxetine, sertraline, and citalopram produce a statistically significant increase in the ejaculation latency time compared with placebo.

CONCLUSIONS

Taking advantage of the ejaculation-delaying effects of SSRIs increases the treatment options available to prescribers and patients. Convenience and minimal adverse effect profile make these agents an alternative to previously used behavior modalities and older pharmacologic agents. Although some questions still surround the details of their use, SSRIs have the potential to improve the quality of life for men with premature ejaculation and their partners.
Phosphodiesterase 5 Inhibitors for Erectile Dysfunction
Authors: Setter Stephen M , Iltz Jason L , Fincham Jack E , Campbell R Keith , Baker Danial E
Published: June 2005

OBJECTIVE

To review the pharmacologic and clinical trial data of the Food and Drug Administration–approved phosphodiesterase 5 (PDE5) inhibitors for the treatment of erectile dysfunction (ED).

DATA SOURCES

Primary research and review articles were identified through a search of ScienceDirect, PubMed/MEDLINE, and International Pharmaceutical Abstracts (1990–August 2004). The following search terms were used in the Medicine Dentistry and Pharmacology, Toxicology, and Pharmaceutical Sciences subcategories: phosphodiesterase 5 inhibitor, PDE5 inhibitor, erectile dysfunction, sildenafil, vardenafil, tadalafil, prostatectomy, and diabetes. Web of Science (1990–August 2004) was used to search for additional abstracts using the same search terms as above. The package inserts for sildenafil, vardenafil, and tadalafil were also consulted.

STUDY SELECTION AND DATA EXTRACTION

All identified research, review articles, and abstracts were assessed for relevance, and all relevant information was included. Priority was given to the primary medical literature and clinical trial reports.

DATA SYNTHESIS

ED is a common disorder in males with increased prevalence associated with age and presence of cardiovascular disease, prostatectomy, or diabetes mellitus. Sildenafil, vardenafil, and tadalafil are selective PDE5 inhibitors currently available for treatment of ED. Their pharmacology and pharmacokinetics vary slightly, but with potentially important clinical differences in duration of activity; all have similar clinical efficacy and adverse effect profiles in patients with ED of various causes.

CONCLUSIONS

Sildenafil, vardenafil, and tadalafil are safe and effective PDE5 inhibitors for the treatment of ED.
Quality Assurance Instrument Focusing on Patient Counseling
Authors: Puumalainen Inka I , Kause Johanna M , Airaksinen Marja S
Published: June 2005

BACKGROUND

Patient counseling is a professional service provided by community pharmacists. To assess the quality of these services, specific quality assurance instruments are needed.

OBJECTIVE

To develop a validated, easy-to-use patient counseling quality assurance instrument for community pharmacists. The development process was part of a national project to enhance patient counseling in community pharmacies (TIPPA 2000–2003).

METHODS

A modified Delphi method was used with 2 expert panels: Panel 1, consisting of experienced pharmacy practitioners (n = 10), and Panel 2, consisting of academic and professional experts (n = 10). The final consensus was assessed by a Delphi questionnaire round involving both panels, the employers of Panel 1 members (n = 5), and the members of the executive board of the TIPPA project (n = 10), comprising 35 people (response rate 74%; n = 26).

RESULTS

The first Delphi round yielded a high consensus, with the level of agreement varying between 69% and 100%. All but one item met the predefined criteria for approval. A total of 16 indicators were identified in 3 quality dimensions: patient (4 indicators), process (6), and learning and innovations (6). Strategy and vision of the pharmacy in patient counseling formed the core of the instrument.

CONCLUSIONS

The modified Delphi method proved to be applicable in the development process of an instrument assessing patient counseling services. The instrument comprehensively takes into account factors related to quality assurance of counseling practices.
From Practice Research to Public Policy—The Ministerial Summit on Health Research
Authors: Bell Simon
Published: June 2005

OBJECTIVE

To report on the outcomes of discussions on the role of research in the improvement of population health that took place at the Ministerial Summit on Health Research.

DATA SOURCES

Information was gathered from presentations and discussions at the Ministerial Summit on Health Research conducted in Mexico City November 16–20, 2004.

DATA SYNTHESIS

Strategies to strengthen health systems through closer collaboration between researchers and policy makers were debated. Consideration was given to persisting inequalities in health research, including the 10/90 gap (10% of health research expenditure is devoted to diseases responsible for 90% of the world's disease burden), the “know-do” gap (the gap between research knowledge and professional practice), and the divide in access to health information. Adopting measures to address human resource shortages was seen as critical. Participants at the Summit issued “The Mexico Statement on Health Research.”

CONCLUSIONS

All stakeholders must develop the political will to share information, resources, and experiences to ensure that practice research and public policy develop in accordance with patients' needs.
The motif of escape in recent Polish films
Authors: Mazierska Ewa
Published: June 2005

This article discusses the motif of physical and spiritual escape in some recent Polish films, arguing that they pertain to the widespread disappointment with the social reality and express the difficulty of overcoming the problems embedded in living in a post-communist society. It
focuses on three films by directors who made their debut in the first decade of the new millennium: Edi (2002), directed by Piotr Trzaskalski, Zmruż oczy/Squint Your Eyes (2003), directed by Andrzej Jakimowski, and Moje pieczone kurczaki/My Roasted Chickens (2002),
directed by Iwona Siekierzyńska. They were chosen because they exemplify a certain tendency in new Polish cinema and were critically and commercially successful, gaining awards in national and international festivals and enjoying good figures at the box office, particularly amongst
younger audiences.
New-ness, Sequelization, and Dogme logic in Kristian Levring’s The King is Alive
Authors: Jess Carolyn
Published: June 2005

This article discusses the workings of aesthetic death and rebirth in one of the most recent manifesto-movements, Dogme 95. Founded on what appears to be an insistent opposition to the sequel phenomenon in recent cinema culture, Dogme’s uniform methods of film production exit from the throng of cinematic ‘likenesses’ to create and champion ‘new-ness’. The Dogme ‘phenomenon’ is argued in this light to invoke many of the patterns that it claims to oppose. The sequel is further regarded in this article as a vehicle for the interrogation and reassessment of the concept of ‘original’ in order to establish a set of differences, to query the ‘authority’ of an auteur, and to impose a new set of (seemingly relevant) methodologies upon a production previously prescribed to the popular consciousness. By pronouncing both the sequel phenomenon and the auteur as irrevocably ‘dead’, the film offers Dogme’s manifesto as a replacement by which ‘new-ness’ and collaborative production can lay the foundations for a ‘new’ cinematic aesthetic in the manner of its new wave predecessors.
Giordana’s I cento passi: renegotiating the Mafia codes
Authors: Small Pauline
Published: June 2005

The ‘codes’ to which the title of this article refers are the narrative and visual codes of a particular genre model, the Mafia film. The article traces the tradition of Mafia film-making with the purpose of establishing how it gives meaning to Marco Tullio Giordana’s
film I cento passi, which is shown to be one of a crop of contemporary Italian films that addresses the Mafia question from a new perspective - through humour (Roberto Benigni, Robert Torre) or through emphasis on a little-known protagonist (Scimeca, Giordana). Giordana’s film
is shown to renegotiate, through intertextual citation, the cinematic codes of Hollywood (Coppola’s The Godfather) and of the European tradition (the films of Francesco Rosi). The article concludes by demonstrating that the impetus behind the current films is found in the climate
of anti-Mafia opinion that predominated in Sicily, following the Mafia murders of judges Giovanni Falcone and Paolo Borsellino in 1992.
‘You want to torture Zora?’ Olivier Assayas’s Demonlover as critique
Authors: Walden Elizabeth
Published: June 2005

Demonlover represents Olivier Assayas’s attempt to find the appropriate filmic structure and themes to depict the complexity of the present intensive form of global consumer capitalism. He uses a structure which plays with genre expectations and borders on incoherence in
order to capture a sense of the social totality and its psycho-sexual investments. Themes of violence, humiliation, torture and sexual fantasy are used to register the complicity of the viewer, while providing the means for an immanent critique of the disturbing world the film depicts.
Multicomponent protein adsorption in supported cationic polyacrylamide hydrogels
Authors: Russell Shawn M. , Carta Giorgio
Published: June 2005

Partitioning and transport of proteins in charged polyacrylamide gels were studied for single and two‐component protein mixtures. The gels were synthesized within fused‐silica capillaries allowing a direct microscopic determination of concentration profiles in the gel during adsorption and desorption of fluorescently labeled proteins. α‐lactalbumin, ovalbumin, and BSA were used as model proteins spanning molecular masses between 15 and 65 kDa. The proteins were conjugated to green and red rhodamine fluorescent labels, allowing simultaneous and independent determinations of two proteins during binary adsorption. The proteins were found to be favorably but reversibly partitioned into the gel and could be eluted at high salt concentrations. The transient concentration profiles were found to be consistent with a Fickian diffusion model with a driving force based on the adsorbed phase concentration gradient. The diffusivity and adsorption capacity of the proteins determined from the microscopic data compared favorably to results previously obtained from macroscopic studies of Q‐HyperD, a gel‐filled particle chemically similar to the gels synthesized in this work. Coadsorption and sequential adsorption experiments also resulted in diffuse concentration profiles indicating that the underlying transport mechanism is the same as for single component transport. The diffusion model was extended to predict the two‐component cases. Predictions were reasonably accurate for co‐adsorption, but gave rates higher than seen experimentally for sequential adsorption, probably as a result of diffusion flux coupling or other nonidealities. © 2005 American Institute of Chemical Engineers AIChE J, 2005
Nonlinear adaptive model predictive control based on self‐correcting neural network models
Authors: Alexandridis Alex , Sarimveis Haralambos
Published: June 2005

Two major issues in process control are the nonlinearities and variations with time that are observed in the dynamics of the processes. In most cases these problems are confronted by robust linear controllers, which are frequently retuned to take into account changes in the operating region or the system dynamics. Obviously, the performance of these controllers is limited by the degree of nonlinearities and the frequency of process variations. In this paper we present a new model predictive control (MPC) framework that can deal with both these issues. The proposed methodology is based on a nonlinear dynamic radial basis function (RBF) model of the process that is able to correct itself as new information about the process dynamics becomes available. The adaptive training algorithm that is used is able to update both the structure and the parameters of the RBF model. The typical formulation of the on‐line optimization problem is augmented by a persistent excitation condition that guarantees that enough perturbation is introduced to the system by the control moves. The proposed MPC framework is applied on the digester control problem and proves to be superior to other MPC configurations. © 2005 American Institute of Chemical Engineers AIChE J, 2005
The new Wolf–Hirschhorn syndrome critical region (WHSCR‐2): A description of a second case
Authors: Rodríguez Laura , Zollino Marcella , Climent Salvador , Mansilla Elena , López‐Grondona Fermina , Martínez‐Fernández María Luisa , Murdolo Marina , Martínez‐Frías María Luisa
Published: June 2005

The Wolf–Hirschhorn syndrome (WHS), is a well known contiguous gene syndrome characterized by microcephaly, hypertelorism, prominent glabella, epicanthal folds, cleft lip or palate, cardiac defects, growth and mental retardation and seizures. The currently accepted WHS critical region (WHSCR) is localized between the loci D4S166 and D4S3327, where a deletion seems to generate all the clinical manifestations of the syndrome. Here we present a patient with a subtelomeric deletion of 4p16.3 showing growth and psychomotor delay with a typical WHS facial appearance and two episodes of seizures in conjunction with fever. The high‐resolution G‐banded karyotype was normal. Fluorescence in situ hybridization (FISH) with a set of cosmids from 4p16.3, showed that the deletion in this patient was from the D4S3327 to the telomere, enabling the size of the deletion to be estimated as 1.9 Mb, excluding the accepted WHSCR deletion. This patient supports the recent proposal by Zollino et al. [2003] that the critical region for WHS is located distally to the WHSCR between the loci D4S3327 and D4S98‐D4S16, and it is called “WHSCR‐2” [Zollino et al., 2003]. © 2005 Wiley‐Liss, Inc.
Characterization of six marker chromosomes by comparative genomic hybridization
Authors: Belloso J.M. , Caballín M.R. , Gabau E. , Baena N. , Vidal R. , Villatoro S. , Guitart M.
Published: June 2005

We applied comparative genomic hybridization (CGH) in six patients with de novo prenatal or postnatal extra marker chromosomes (MC). In four cases, MCs were mosaic and in one of them, the MC was detected in less than 50% of the cells. In three cases, CGH identified the origin of the extra MCs. In the other three, two prenatal cases and one child with an abnormal phenotype, CGH showed normal profiles. Among these cases, a normal profile and entirely C‐band positive was identified suggesting that MC did not contain euchromatin. Genetic imbalances detected by CGH were as follow: a gain of 8p10‐p12 in a boy with facial dysmorphism, hyperactivity and speech delay, a gain of 8q10‐q12 in a healthy man with a history of spontaneous abortions, and a gain of 15q11‐q13 in a girl with speech delay, and motor skill and object manipulation difficulties. Clinical data of these patients were compared with those reported in the literature. We conclude that CGH is a very useful and powerful tool for characterizing prenatal or postnatal MCs, even when the mosaicism is present and the MCs are present in less than 50% of the cells. © 2005 Wiley‐Liss, Inc.
CDG‐IL: An infant with a novel mutation in theALG9gene and additional phenotypic features
Authors: Weinstein Michael , Schollen Els , Matthijs Gert , Neupert Christine , Hennet Thierry , Grubenmann Claudia E. , Frank Christian G. , Aebi Markus , Clarke Joe T. R. , Griffiths Anne , Seargeant Lorne , Poplawski Nicola
Published: June 2005

We describe the second case of congenital disorder of glycosylation type IL (CDG‐IL) caused by deficiency of the ALG9 a1,2 mannosyltransferase enzyme. The female infant's features included psychomotor retardation, seizures, hypotonia, diffuse brain atrophy with delayed myelination, failure to thrive, pericardial effusion, cystic renal disease, hepatosplenomegaly, esotropia, and inverted nipples. Lipodystrophy and dysmorphic facial features were absent. Magnetic resonance imaging of the brain showed volume loss in the cerebral hemispheres and cerebellum and delayed myelination. Laboratory investigations revealed low levels of multiple serum proteins including antithrombin III, factor XI, and cholesterol. Hypoglycosylation was confirmed by the typical CDG type 1 pattern of serum transferrin analyzed by isoelectric focusing. A defect in the ALG9 enzyme was suggested by the accumulation of the DolPP‐GlcNAc2Man6 and DolPP‐GlcNAc2Man8 in the patient's fibroblasts and confirmed by mutation analysis: the patient is homozygous for theALG9mutation p.Y286C. The causal effect of the mutation was shown by complementation assays in alg9 deficient yeast cells. The child described here further delineates the clinical spectrum of CDG‐IL and confirms the significant clinical overlap amongst CDG subtypes. © 2005 Wiley‐Liss, Inc.
Fortschritte bei katalytischen enantioselektiven α‐Aminierungen und α‐Oxygenierungen von Carbonylverbindungen
Authors: Janey Jacob M.
Published: June 2005

Die direkte Einführung eines Stickstoff‐ oder Sauerstoffatoms in Nachbarschaft zu einer Carbonylfunktion auf katalytische und enantioselektive Weise – sowohl durch chirale Lewis‐Säure‐ als auch Lewis‐Base‐Katalyse – wurde unlängst beschrieben. Die enantiomerenangereicherten Produkte dieser Reaktionen, unter anderem α‐Aminosäuren, bilden Grundbausteine für die Synthese komplexer Naturstoffe und anderer wichtiger bioaktiver Moleküle. Dieser Kurzaufsatz fasst das ständig wachsende Gebiet zusammen und weist auf einige offene Fragen hin.
Recent Advances in Catalytic, Enantioselective α Aminations and α Oxygenations of Carbonyl Compounds
Authors: Janey Jacob M.
Published: June 2005

The direct introduction of either a nitrogen or oxygen atom adjacent to a carbonyl group in a catalytic, enantioselective manner using both chiral Lewis acid and Lewis base catalysis has been described recently. The enantiomerically enriched products of these reactions, such as α‐amino acids, represent fundamental building blocks for the construction of complex natural products and other important bioactive molecules. This Minireview provides a synopsis of this ever‐growing field and highlights some of the challenges that still remain.
Numerische Modellierung von Holz und Verbindungselementen in Holz‐Beton‐Verbundkonstruktionen
Authors: Grosse Marco , Rautenstrauch Karl , Schlegel Roger
Published: June 2005

Durch die Anwendung der FEM können auch komplexe Strukturen berechnet werden, die sich nicht mehr als Stab‐ oder Flächentragwerke abbilden lassen. Es ist daher naheliegend, auch das Tragverhalten von Bauteilen oder Bauteilkomponenten in Abhängigkeit von verschiedenen Einflußparametern mit Hilfe von FE‐Modellen zu simulieren. Um dabei aber Versagensmechanismen abbilden zu können, ist es notwendig, das Materialverhalten der Baustoffe im Nachbruchbereich zu berücksichtigen. Es wird ein konstitutives Materialmodell für den Werkstoff Holz vorgestellt, welches das räumlich anisotrope und vom Beanspruchungsmodus abhängige, nichtlineare Tragverhalten einbezieht. Durch die Kombination mit einem leistungsfähigen Betonmodell ist es möglich, Holz‐Beton‐Verbundkonstruktionen zu untersuchen. Anhand der Simulationen von Scherversuchen mit verschiedenen Schubverbindungselementen soll die Leistungsfähigkeit solcher numerischer Modelle verdeutlicht werden.
Industrial process proteomics: Alfalfa protein patterns during wet fractionation processing
Authors: Incamps Anne , Hély‐Joly Florence , Chagvardieff Pierre , Rambourg Jean‐Claude , Dedieu Alain , Linares Elodie , Quéméneur Eric
Published: June 2005

A proteome reference map of major soluble proteins from Medicago sativa (alfalfa) leaves and stems has been established for the first time. Among 195 spots analyzed by mass spectrometry and N‐terminal Edman sequencing, 117 spots were unambiguously identified, representing 87 different proteins. Of these 87 proteins, 13 proteins were directly identified from the partial genome of Medicago sativa, 30 from expressed sequenced tags (ESTs) of the model legume Medicago truncatula and 44 from closely relative species by a cross‐species protein identification method. The proteome map of Medicago sativa was then set as a reference to study the major high protein content products that are generated during the wet fractionation process of alfalfa green biomass. Using two‐dimensional electrophoresis, we studied the variation of the protein patterns at different steps of the industrial‐scale process. We clearly show that the process induces significant changes including chemical modifications, proteolytic events, and heat‐shock protein responses. Strikingly, a certain level of cellular regulation is conserved during biomass processing, as exemplified by the induction of some heat shock proteins. Finally, all the results obtained in this proteomic study may help to identify novel products and to improve process designs in alfalfa biomass plants. © 2005 Wiley Periodicals, Inc.
Epi‐CHO, an episomal expression system for recombinant protein production in CHO cells
Authors: Kunaparaju Rajkumar , Liao Mimi , Sunstrom Noelle‐Anne
Published: June 2005

This study describes the development of a transient expression system for CHO cells based on autonomous replication and retention of transfected plasmid DNA. A transient expression system that allows extrachromosomal amplification of plasmids permits more plasmid copies to persist in the transfected cell throughout the production phase leading to a significant increase in transgene expression. The expression system, named Epi‐CHO comprises (1) a CHO‐K1 cell line stably transfected with the Polyomavirus (Py) large T (LT) antigen gene (PyLT) and (2) a DNA expression vector, pPyEBV encoding the Py origin (PyOri) for autonomous plasmid amplification and encoding Epstein‐Barr Virus (EBV) nuclear antigen‐1 (EBNA‐1) and OriP for plasmid retention. The CHO‐K1 cell line expressing PyLT, named CHO‐T was adapted to suspension growth in serum‐free media to facilitate large‐scale transient transfection and recombinant gene expression. Enhanced green fluorescent protein (EGFP) and human growth hormone (hGH) were used as reporter proteins to demonstrate transgene expression and productivity. Transfection of suspension‐growing CHO‐T cells with the vector pPyEBV encoding hGH resulted in a final concentration of 75 mg L−1 of hGH in culture supernatants 11 days following transfection. © 2005 Wiley Periodicals, Inc.
Critical influence of Eschscholzia californica cells nutritional state on secondary metabolite production
Authors: Lamboursain Laurence , Jolicoeur Mario
Published: June 2005

In this study, we investigated the influence of initial internal nutrient concentrations at the time of elicitation on the ability of Eschscholzia californica (EC) cells to produce alkaloids. Three EC cell suspensions cultivated in culture media differing in their PO and NO contents were sampled daily for 12 days and analyzed for extracellular and intracellular nutrient concentrations. The ability of the cells to produce alkaloids was tested along the three cell suspension cultures. Sampled cells were then further cultured for 7 days in a production medium containing the elicitor and an extraction resin. The alkaloid production of the cells was measured 7 days post‐elicitation. In the low‐N medium, starch, glucose, and phosphate contents in the biomass was increased by 470, 1624 and 70%, respectively, 10 days after inoculation compared to the control culture in standard B5 medium. Cell concentration was significantly reduced from 10.3 to 8.6 millions cell/mL on this low‐N medium compared to the control, nevertheless alkaloid production was multiplied by 39 at day 10 when cells were elicited. Cells grown on the low‐N or low‐P media accumulated 83% and 188% more carbon, respectively, than control cells at the end of the culture. This intracellular C was mainly stored in the form of starch in low‐P medium and both in the form of starch and glucose in the low‐N medium. The ability of EC cells to produce alkaloids upon elicitation was shown to be strongly dependent on the initial intracellular C and P content at the time of elicitation. This suggests that reproducibility and productivity during EC cell culture could be enhanced by manipulating the intracellular C and P content at the time of elicitation. © 2005 Wiley Periodicals, Inc.
Effects of protein–protein interaction in ultrafiltration based fractionation processes
Authors: Filipe Carlos DM , Ghosh Raja
Published: June 2005

This paper discusses the use of pulsed sample injection ultrafiltration (UF) for investigating protein–protein interaction, particularly its effect on protein transmission through UF membranes. Several binary protein mixtures were investigated; the proteins in each mixture being selected such that one of the proteins in the pair would be preferentially transmitted while the other would be either totally or substantially retained. The “retained” protein either decreased or increased or did not affect the sieving coefficient of the “transmitted” protein, this depending the type of protein–protein interaction, that is, associative, repulsive, or neutral. The type of protein–protein interaction depended on the particular protein pair under investigation as well as on the operating conditions used (pH and salt concentration). The magnitude of either decrease or increase in transmission of a preferentially transmitted protein due to the presence of a retained protein was found to be independent of the manner in which the proteins were injected into the system, that is, simultaneous or sequential. These magnitudes however correlated well with the ratio of the two proteins present in the feed. © 2005 Wiley Periodicals, Inc.
Detachment and emission of airborne bacteria in gas‐phase biofilm reactors
Authors: Zilli Mario , Camogli Gianluca , Nicolella Cristiano
Published: June 2005

Three laboratory scale biofilters filled with different packing materials (peat and sieved sugarcane bagasse) and operating with different microbial cultures (allochthonous and autochthonous bacteria) were run and monitored in parallel to assess the emission rate of airborne bacteria in the biofiltration of benzene‐contaminated air streams. The effect of the fluid dynamic and loading conditions on the rate of microbial emission in the air environment was investigated by performing continuous experiments at different inlet benzene concentrations and superficial gas velocities. The experiments prove that the concentration of airborne bacteria in the effluent air from lab‐scale biofilters is only slightly higher than in the ambient air. The emission rate is not dependent on superficial gas velocity because of low shear stress exerted by the gas flow. On the other hand, the loading conditions have a strong effect on the emission rate, which increases with increasing growth and degradation rate, and different packing media show remarkably different behaviors. © 2005 Wiley Periodicals, Inc.
Integration of gene expression profiling and clinical variables to predict prostate carcinoma recurrence after radical prostatectomy
Authors: Stephenson Andrew J. , Smith Alex , Kattan Michael W. , Satagopan Jaya , Reuter Victor E. , Scardino Peter T. , Gerald William L.
Published: June 2005

BACKGROUND

Gene expression profiling of prostate carcinoma offers an alternative means to distinguish aggressive tumor biology and may improve the accuracy of outcome prediction for patients with prostate carcinoma treated by radical prostatectomy.

METHODS

Gene expression differences between 37 recurrent and 42 nonrecurrent primary prostate tumor specimens were analyzed by oligonucleotide microarrays. Two logistic regression modeling approaches were used to predict prostate carcinoma recurrence after radical prostatectomy. One approach was based exclusively on gene expression differences between the two classes. The second approach integrated prognostic gene variables with a validated postoperative predictive model based on standard variables (nomogram). The predictive accuracy of these modeling approaches was evaluated by leave‐one‐out cross‐validation (LOOCV) and compared with the nomogram.

RESULTS

The modeling approach using gene variables alone accurately classified 59 (75%) tissue samples in LOOCV, a classification rate substantially higher than expected by chance. However, this predictive accuracy was inferior to the nomogram (concordance index, 0.75 vs. 0.84, P = 0.01). Models combining clinical and gene variables accurately classified 70 (89%) tissue samples and the predictive accuracy using this approach (concordance index, 0.89) was superior to the nomogram (P = 0.009) and models based on gene variables alone (P < 0.001). Importantly, the combined approach provided a marked improvement for patients whose nomogram‐predicted likelihood of disease recurrence was in the indeterminate range (7‐year disease progression‐free probability, 30–70%; concordance index, 0.83 vs. 0.59, P = 0.01).

CONCLUSIONS

Integration of gene expression signatures and clinical variables produced predictive models for prostate carcinoma recurrence that perform significantly better than those based on either clinical variables or gene expression information alone. Cancer 2005. © 2005 American Cancer Society.