bluuebunny/crossref_metadata_2025 huggingface dataset:
C-peptide increases the expression of vasopressin-activated calcium-mobilizing receptor gene through a G protein-dependent pathway
Authors: Maestroni Anna , Ruggieri Dora , Dell’Antonio Giacomo , Luzi Livio , Zerbini Gianpaolo
Published: January 2005

Objective: Although an increasing number of reports suggest that physiological concentrations of C-peptide protect against the development of diabetic nephropathy, possibly through the modulation of Na–K pump activity, the intracellular pathways controlled by C-peptide are still unrecognized. C-peptide and vasopressin share similar intracellular effects including the activation of calcium influx and endothelial nitric oxide synthase. Both hormones stimulate also the activity of Na–K pump activity. Whether the activity of C-peptide is mediated by the recently identified vasopressin-activated calcium-mobilizing receptor (VACM-1) has never been previously investigated.

Design and methods: To clarify this issue, we evaluated the effect of C-peptide on VACM-1 RNA (measured by semiquantitative RT-PCR) and protein expression (measured by immunoblotting) in human skin fibroblasts (where a specific binding of C-peptide was demonstrated) and in human mesangial cells, the cellular target of diabetic nephropathy.

Results: C-peptide-induced activation of VACM-1 was demonstrated in fibroblasts from six healthy individuals (0.51±0.1 vs 1.48±0.4, arbitrary units±s.e.,P= 0.025). This finding was paralleled by an increased VACM-1 protein expression (5.64±1.0 vs 8.47±1.2, arbitrary units±s.e.,P= 0.043). Similar results were confirmed in three independent cultures of human mesangial cells. VACM-1 activation in fibroblasts was insensitive to phosphatidylinositol-3-kinase inhibitor LY294002, but was inhibited by pertussis toxin, suggesting that activation of VACM-1 could be mediated by a G protein-coupled receptor.

Conclusions: This study demonstrates for the first time that C-peptide activates VACM-1, possibly through a G protein-coupled receptor. Further studies are needed to clarify whether VACM-1 is involved in the protective effect of C-peptide against the development of diabetic nephropathy.
Gross total resection or debulking of pituitary adenomas improves hormonal control of acromegaly by somatostatin analogs
Authors: Petrossians Patrick , Borges-Martins Liliane , Espinoza Consuelo , Daly Adrian , Betea Daniela , Valdes-Socin Hernan , Stevenaert Achille , Chanson Philippe , Beckers Albert
Published: January 2005

Introduction:Invasive GH-secreting pituitary adenomas are rarely cured by surgery and although long-term therapy with somatostatin analogs (SSAs) may be employed, hormonal control is achieved in only 60% of cases. The impact of tumor debulking on subsequent control of acromegaly with SSAs has not been studied previously.

Methods:We studied retrospectively the response to SSA therapy in acromegalic patients before and after incomplete surgical tumor excision. A case review identified 24 acromegalic patients who had received SSA therapy for ≥1 month before and after gross total resection or debulking of adenomas. No patient received radiotherapy or combination treatment with SSAs and dopamine agonists during the study. GH and IGF-I responses to SSAs were recorded pre- and postoperatively. Postoperative SSA therapy was begun after a washout period of 1–3 months to assess the hormonal effects of the surgery alone.

Results:Before preoperative SSA treatment, 24/24 (100%) patients had elevated GH levels and IGF-I levels were elevated in 19/21 (90.5%) patients with recorded values. During preoperative SSA treatment, GH and IGF-I levels were normalized in 7/24 (29.2%) and 11/24 (45.8%) patients respectively. Following postoperative washout, GH was controlled in only 3/24 (12.5%) patients, while IGF-I was controlled in 8/19 (42.1%) patients with available data. During the second SSA treatment period, normal GH levels were seen in 13/24 (54.2%) patients, while IGF-I control was noted in 18/23 (78.3%).

Conclusion:Gross total tumor resection or debulking increases the likelihood of achieving biochemical disease control with SSAs in acromegalic patients with adenomas that were not amenable to complete surgical resection and in whom primary SSA therapy was unable to achieve good biochemical control.
Increased prevalence of catecholamine excess and phaeochromocytomas in a well-defined Dutch population with SDHD-linked head and neck paragangliomas
Authors: van Houtum W H , Corssmit E P M , Douwes Dekker P B , Jansen J C , van der Mey A G L , Bröcker-Vriends A H J T , Taschner P E M , Losekoot M , Frölich M , Stokkel M P M , Cornelisse C J , Romijn J A
Published: January 2005

Objective: The aim of this study was to identify the prevalence of catecholamine excess and phaeochromocytomas in a well-defined population of people with hereditary head and neck paragangliomas.

Methods: We studied in a prospective follow-up protocol all consecutive patients referred to the Department of Endocrinology, Leiden University Medical Center, Leiden, The Netherlands with documented head and neck paragangliomas and either a positive family history for paragangliomas or a provenSDHDgene mutation. Initial analysis included medical history, physical examination and the measurement of excretion of catecholamines in two 24-h urine collections. In the case of documented catecholamine excess iodinated meta-iodobenzylguanidine (123I-MIBG) scintigraphy and magnetic resonance imaging were done.

Results: Between 1988 and 2003, 40 consecutive patients (20 male and 20 female) with documented head and neck paragangliomas were screened. Biochemical screening revealed urinary catechol-amine excess in 15 patients (37.5%). In nine of these 15 patients a lesion was found by123I-MIBG scintigraphy. Exact localization by magnetic resonance imaging revealed phaeochromocytomas in seven of the 15 patients. One of the nine patients had an extra-adrenal paraganglioma. Histopathological examination in a subset of tumors displayed loss of heterozygosity of the wild-typeSDHDallele in all cases.

Conclusions: The prevalence of catecholamine excess (37.5%) and phaeochromocytomas (20.0%) is high in patients with familial head and neck paragangliomas. Therefore, patients with hereditary head and neck paragangliomas require lifelong follow up by biochemical testing for catecholamine excess.
Evidence against a role of human airway trypsin-like protease – the human analogue of the growth-promoting rat adrenal secretory protease – in adrenal tumourigenesis
Authors: Hahner Stefanie , Fassnacht Martin , Hammer Fabian , Schammann Markus , Weismann Dirk , Hansen Immo Alex , Allolio Bruno
Published: January 2005

Objective: A serine protease from rat adrenal cortex was recently characterized and named adrenal secretory protease (AsP). AsP is expressed in the adrenal cortex and is capable of cleaving pro-γ-melanocyte-stimulating hormone (1-76 N-terminus of pro-opiomelanocortin) into fragments that act as adrenal mitogens. AsP may therefore play a crucial role in adrenal growth and tumourigenesis. The aim of this study was to further characterize the human homologue of AsP and its possible role in adrenal tumourigenesis.

Methods and results: Starting with the rat cDNA sequence of AsP we detected high homology to the catalytic C-terminus of the human airway trypsin-like protease (HAT). Further analysis revealed that the HAT gene is the human homologue of a long splice variant of AsP, which we recently described as rat airway trypsin-like serine protease 1. In contrast to rodents, no short isoform of HAT was found in humans due to a stop codon in exon 6 which prevents the expression of a short isoform. While high expression of HAT mRNA was found in the trachea and in the gastrointestinal tract, expression in the adrenal was only very weak. RT-PCR and real-time PCR analysis revealed a complex tissue expression pattern of HAT, indicating a role for this protease in multiple tissues. We further investigated HAT expression in five normal adrenal glands, 15 adrenocortical adenomas (five hormonally inactive adenomas, five aldosterone-producing adenomas and five cortisol-producing adenomas), nine adrenocortical carcinomas, five phaeochromocytomas and two adrenal hyperplasias. Weak HAT expression was detectable in only two out of five normal adrenal glands, in one out of twenty-four adrenocortical tumours and four out of five phaeochromocytomas. However, the expression in the adrenal tissue was several orders of magnitude lower than in the trachea. In addition, we could not detect any HAT transcripts in a sample of fetal adrenal.

Conclusion: Gene structure and tissue distribution of HAT, the human homologue of the rat adrenal secretory protease AsP, reveal major interspecies differences. The observation of very low expression levels in normal adrenal tissue and adrenocortical tumours casts doubt about a role for HAT in the physiological and pathological growth of adrenocortical cells.
Epidermal growth factor receptor inhibition strategies in oncology
Authors: Harari P M
Published: January 2005

Molecular targeting strategies for cancer therapy are distinct from conventional chemotherapy and radiotherapy in their potential to provide increased tumor specificity. One particular molecular target of high promise in oncology is the epidermal growth factor receptor (EGFR). The EGFR is overexpressed, dysregulated or mutated in many epithelial malignancies, and EGFR activation appears important in tumor growth and progression. Advances in signal transduction biology continue to sharpen our understanding regarding specific contributions of EGFR signaling networks to cancer behavior. Two predominant classes of EGFR inhibitors have been developed including monoclonal antibodies (mAbs) that target the extracellular domain of EGFR, such as cetuximab (Erbitux), and small molecule tyrosine kinase inhibitors (TKIs) that target the receptor catalytic domain of EGFR, such as gefitinib (Iressa) and erlotinib (Tarceva).

Mechanisms of action for EGFR inhibitors have been investigated in preclinical model systems. Safety, activity, pharmacokinetics and pharmacodynamics have been assessed in clinical trials. The anti-EGFR mAbs and TKIs have partially overlapping toxicity profiles, but distinct routes of administration, serum half-lives and therefore dosing schedules. Both classes of agents show clear antitumor activity, and cetuximab and gefitinib have been recently FDA approved for colorectal and lung cancer indications respectively. However, the absence of survival benefit for EGFR TKIs in combination with chemotherapy in large-scale phase III lung cancer trials in 2003 underscores a major challenge in anti-EGFR oncology therapeutics; namely to identify those tumors and patients that will respond predictably to EGFR inhibitor approaches. Newly identified mutations in the EGFR catalytic domain that appear to confer sensitivity to EGFR TKIs promise to open new doors of investigation regarding response prediction. Advances will also require enhanced molecular understanding of the overall EGFR signaling network, and improved methods to gauge the dependence of individual tumors on EGFR signaling pathways for growth advantage. Results from newly reported phase III trials in 2004 now confirm a survival advantage for the use of EGFR inhibitors in combination with high-dose radiation in head and neck cancer, and in refractory lung cancer respectively. It appears likely that EGFR inhibitors (and other rationally designed molecular growth inhibitors) will play a meaningful role in cancer therapy in the years to come.
Gonadotropin-releasing hormone and its receptor in normal and malignant cells
Authors: Harrison G S , Wierman M E , Nett T M , Glode L M
Published: January 2005

Gonadotropin-releasing hormone (GnRH) is the hypothalamic factor that mediates reproductive competence. Intermittent GnRH secretion from the hypothalamus acts upon its receptor in the anterior pituitary to regulate the production and release of the gonadotropins, LH and FSH. LH and FSH then stimulate sex steroid hormone synthesis and gametogenesis in the gonads to ensure reproductive competence. The pituitary requires pulsatile stimulation by GnRH to synthesize and release the gonadotropins LH and FSH. Clinically, native GnRH is used in a pump delivery system to create an episodic delivery pattern to restore hormonal defects in patients with hypogonadotropic hypogonadism. Agonists of GnRH are delivered in a continuous mode to turn off reproductive function by inhibiting gonadotropin production, thus lowering sex steroid production, resulting in medical castration. They have been used in endocrine disorders such as precocious puberty, endometriosis and leiomyomata, but are also studied extensively in hormone-dependent malignancies. The detection of GnRH and its receptor in other tissues, including the breast, ovary, endometrium, placenta and prostate suggested that GnRH agonists and antagonists may also have direct actions at peripheral targets. This paper reviews the current data concerning differential control of GnRH and GnRH receptor expression and signaling in the hypothalamic–pituitary axis and extrapituitary tissues. Using these data as a backdrop, we then review the literature about the action of GnRH in cancer cells, the utility of GnRH analogs in various malignancies and then update the research in novel therapies targeted to the GnRH receptor in cancer cells to promote anti-proliferative effects and control of tumor burden.
Mechanisms of desensitization of the adrenocorticotropin response to arginine vasopressin in ovine anterior pituitary cells
Authors: Hassan A , Mason D
Published: January 2005

Arginine vasopressin (AVP) stimulates adrenocorticotropin (ACTH) secretion from corticotroph cells of the anterior pituitary via activation of the V1b vasopressin receptor, a member of the G protein-coupled receptor (GPCR) family. Recently, we have shown that treatment of ovine anterior pituitary cells with AVP for short periods results in reduced responsiveness to subsequent stimulation with AVP. The aim of this study was to investigate mechanisms involved in this desensitization process. Among the GPCR family, rapid desensitization is commonly mediated by receptor phosphorylation, with resensitization being mediated by internalization and subsequent dephosphorylation of the receptors by protein phosphatases. Since desensitization of V1a vasopressin receptors is mediated by protein kinase C-mediated receptor phosphorylation, we investigated the involvement of this enzyme in desensitization of the ACTH response to AVP. Treatment of perifused ovine anterior pituitary cells with the specific protein kinase C (PKC) activator 1,2-dioctanoyl-sn-glycerol (300 μM) did not induce any reduction in response to a subsequent 5-min stimulation with 100 nM AVP, despite potently stimulating ACTH secretion. Likewise, the results obtained using the PKC inhibitor Ro 31-8220 were not consistent with involvement of PKC in AVP desensitization: 2 μM Ro 31-8220 did not reduce the ability of a 10 nM AVP pretreatment to induce desensitization to a subsequent stimulation with 100 nM AVP. Pharmacologic blockade of receptor internalization by treatment with 0.25 mg/ml concanavalin A significantly impaired the ability of a 15-min pretreatment with 10 nM AVP to induce desensitization, rather than affecting resensitization. Treatment with 10 nM okadaic acid, an inhibitor of protein phosphatase 1 and 2A, had no effect on either resensitization or desensitization. In contrast, inhibition of protein phosphatase 2B (PP2B) with 1 μM FK506 decreased the rate of resensitization: complete recovery from desensitization took 40 min, whereas in controls recovery was complete 20 min after termination of the pretreatment. These results indicate that desensitization of the ACTH response to AVP is not mediated by PKC-catalyzed phosphorylation, suggesting subtype-specific differences in the regulation of V1a and V1b vasopressin receptors. The data demonstrate that desensitization was dependent, at least in part, upon receptor internalization and that resensitization was dependent upon PP2B-mediated receptor dephosphorylation.
Salmon serum 22 kDa insulin-like growth factor-binding protein (IGFBP) is IGFBP-1
Authors: Shimizu M , Dickey J T , Fukada H , Dickhoff W W
Published: January 2005

Western ligand blotting of salmon serum typically reveals three insulin-like growth factor (IGF) binding proteins (IGFBPs) at 22, 28 and 41 kDa. Physiologic regulation of the 22 kDa IGFBP is similar to that of mammalian IGFBP-1; it is increased in catabolic states such as fasting and stress. On the other hand, its molecular mass on Western ligand blotting is closest to mammalian IGFBP-4. The conflict between physiology and molecular mass makes it difficult to determine the identity of the 22 kDa IGFBP. This study therefore aimed to identify the 22 kDa IGFBP from protein and cDNA sequences. The 22 kDa IGFBP was purified from chinook salmon serum by a combination of IGF-affinity chromatography and reverse-phase chromatography. The N-terminal aminoacid sequence of the purified protein was used to design degenerate primers. Degenerate PCR with liver template amplified a partial IGFBP cDNA, and full-length cDNA was obtained by 5′- and 3′-rapid amplification of cDNA ends (RACE). The 1915-bp cDNA clone encodes a 23.8 kDa IGFBP, and its N-terminal amino-acid sequence matched that of purified 22 kDa IGFBP. Sequence comparison with six human IGFBPs revealed that it is most similar to IGFBP-1 (40% identity and 55% similarity). These findings indicate that salmon 22 kDa IGFBP is IGFBP-1. Salmon IGFBP-1 mRNA is predominantly expressed in the liver, and its expression levels appear to reflect circulating levels. The 3′-untranslated region of salmon IGFBP-1 mRNA contains four repeats of the nucleotide sequence ATTTA, which is involved in selective mRNA degradation. In contrast, amino-acid sequence analysis revealed that salmon IGFBP-1 does not have an Arg-Gly-Asp (RGD) integrin recognition sequence nor a Pro, Glu, Ser and Thr (PEST)-rich domain (a segment involved in rapid turnover of protein), both of which are characteristic of mammalian IGFBP-1. These findings suggest that association with the cell surface and turnover rate may differ between salmon and mammalian IGFBP-1.
Hypothalamic hormones a.k.a. hypothalamic releasing factors
Authors: Guillemin Roger
Published: January 2005

Originally searched for and eventually isolated as factors of hypothalamic origin controlling anterior pituitary secretions, these hypophysiotropic peptides are now a chapter of physiology and medical endocrinology of their own. Defying the concept of ‘neuropeptides’ they and their receptors are now known to be ubiquitous and to have subtle as well as profound effects on a large number of functions of both soma and psyche. This review will be composed of brief essays on current knowledge of each of the original ‘hypothalamic hormones’, TRH, GnRH, somatostatin, GHRH and corticotropin releasing hormone and will close on possible and probable futures.
Temporal profiling of the transcriptional basis for the development of corticosteroid-induced insulin resistance in rat muscle
Authors: Almon Richard R , DuBois Debra C , Jin Jin Y , Jusko William J
Published: January 2005

Elevated systemic levels of glucocorticoids are causally related to peripheral insulin resistance. The pharmacological use of synthetic glucocorticoids (corticosteroids) often results in insulin resistance/type II diabetes. Skeletal muscle is responsible for close to 80% of the insulin-induced systemic disposal of glucose and is a major target for glucocorticoid-induced insulin resistance. We used Affymetrix gene chips to profile the dynamic changes in mRNA expression in rat skeletal muscle in response to a single bolus dose of the synthetic glucocorticoid methyl-prednisolone. Temporal expression profiles (analyzed on individual chips) were obtained from tissues of 48 drug-treated animals encompassing 16 time points over 72 h following drug administration along with four vehicle-treated controls. Data mining identified 653 regulated probe sets out of 8799 present on the chip. Of these 653 probe sets we identified 29, which represented 22 gene transcripts, that were associated with the development of insulin resistance. These 29 probe sets were regulated in three fundamental temporal patterns. 16 probe sets coding for 12 different genes had a profile of enhanced expression. 10 probe sets coding for eight different genes showed decreased expression and three probe sets coding for two genes showed biphasic temporal signatures. These transcripts were grouped into four general functional categories: signal transduction, transcription regulation, carbohydrate/fat metabolism, and regulation of blood flow to the muscle. The results demonstrate the polygenic nature of transcriptional changes associated with insulin resistance that can provide a temporal scaffolding for translational and post-translational data as they become available.
Weight gain associated with the −759C/T polymorphism of the 5HT2C receptor and olanzapine
Authors: Ellingrod Vicki L. , Perry Paul J. , Ringold John C. , Lund Brian C. , Bever‐Stille Kristy , Fleming Frank , Holman Timothy L. , Miller Del
Published: January 2005

Background

Weight gain from atypical antipsychotic use has become a significant problem. Recent reports have liked the −759 polymorphism of the 5HT2C receptor and obesity as well as weight gain from chlorpromazine, risperidone, and clozapine.

Aim

To determine associations between weight gain during olanzapine treatment and the −759C/T polymorphism of the 5HT2C receptor gene.

Methods

This study included 42 acutely ill patients with schizophrenia (DSM‐IV). Weekly assessments included Brief Psychiatric Rating Scale (BPRS), Scale for Assessment of Negative Symptoms (SANS), and weight measurements. Olanzapine was titrated to a fixed dose (7.5–20 mg/day) for 2–6 weeks. A 24 hr plasma level was obtained at the endpoint visit. Genomic DNA was isolated from a whole blood sample and analyzed for the −759C/T polymorphism of the 5HT2C receptor.

Results

A chi‐square analysis was conducted comparing the distribution of T and C alleles in subjects grouped as gaining more or less than 5, 7, and 10% of their baseline weight during treatment with olanzapine. A threshold of 10% was found to be significant. The distribution of T alleles was higher in subjects not gaining 10% of more of their body weight compared who did gain significant weight (11/27 (40.7%) vs. 0/15 (100%), χ2 = 11.805, P = 0.0035).

Conclusions

Subjects with a T allele of the 5HT2C receptor −759C/T polymorphism may have a lower incidence of weight gain from olanzapine over a 6 week period compared to those with the C allele. These results need to be replicated. © 2005 Wiley‐Liss, Inc.
Thermal stability and energetics of 15‐mer DNA duplex interstrand crosslinked by trans‐diamminedichloroplatinum(II)
Authors: Hofr Ctirad , Brabec Viktor
Published: January 2005

The effect of the location of the interstrand cross‐link formed by trans‐diamminedichloroplatinum(II) (transplatin) on the thermal stability and energetics of 15‐mer DNA duplex has been investigated. The duplex containing single, site‐specific cross‐link, thermodynamically equivalent model structures (hairpins) and nonmodified duplexes were characterized by differential scanning calorimetry, temperature‐dependent uv absorption, and circular dichroism. The results demonstrate that the formation of the interstrand cross‐link of transplatin does not affect pronouncedly thermodynamic stability of DNA: the cross‐link induces no marked changes not only in enthalpy, but also in “reduced” (concentration independent) monomolecular transition entropy. These results are consistent with the previous observations that interstrand cross‐links of transplatin structurally perturb DNA only to a relatively small extent. On the other hand, constraining the duplex with the interstrand cross‐link of transplatin results in a significant increase in thermal stability that is primarily due to entropic effects: the cross‐link reduces the molecularity of the oligomer system from bimolecular to monomolecular. Importantly, the position of the interstrand cross‐link within the duplex modulates cooperativity of the melting transition of the duplex and consequently its thermal stability. © 2005 Wiley Periodicals, Inc. Biopolymers, 2005
Wavelength selection with Tabu Search
Authors: Hageman J. A. , Streppel M. , Wehrens R. , Buydens L. M. C.
Published: January 2005

This paper introduces Tabu Search in analytical chemistry by applying it to wavelength selection. Tabu Search is a deterministic global optimization technique loosely based on concepts from artificial intelligence. Wavelength selection is a method which can be used for improving the quality of calibration models. Tabu Search uses basic, problem‐specific operators to explore a search space, and memory to keep track of parts already visited. Several implementational aspects of wavelength selection with Tabu Search will be discussed. Two ways of memorizing the search space are investigated: storing the actual solutions and storing the steps necessary to create them. Parameters associated with Tabu Search are configured with a Plackett–Burman design. In addition, two extension schemes for Tabu Search, intensification and diversification, have been implemented and are applied with good results. Eventually, two implementations of wavelength selection with Tabu Search are tested, one which searches for a solution with a constant number of wavelengths and one with a variable number of wavelengths. Both implementations are compared with results obtained by wavelength selection methods based on simulated annealing (SA) and genetic algorithms (GAs). It is demonstrated with three real‐world data sets that Tabu Search performs equally well as and can be a valuable alternative to SA and GAs. The improvements in predictive abilities increased by a factor of 20 for data set 1 and by a factor of 2 for data sets 2 and 3. In addition, when the number of wavelengths in a solution is variable, measurements on the coverage of the search space show that the coverage is usually higher for Tabu Search compared with SA and GAs. Copyright © 2003 John Wiley & Sons, Ltd.
A robust PCR method for high‐dimensional regressors
Authors: Hubert Mia , Verboven Sabine
Published: January 2005

We consider the multivariate calibration model which assumes that the concentrations of several constituents of a sample are linearly related to its spectrum. Principal component regression (PCR) is widely used for the estimation of the regression parameters in this model. In the classical approach it combines principal component analysis (PCA) on the regressors with least squares regression. However, both stages yield very unreliable results when the data set contains outlying observations. We present a robust PCR (RPCR) method which also consists of two parts. First we apply a robust PCA method for high‐dimensional data on the regressors, then we regress the response variables on the scores using a robust regression method. A robust RMSECV value and a robust R2 value are proposed as exploratory tools to select the number of principal components. The prediction error is also estimated in a robust way. Moreover, we introduce several diagnostic plots which are helpful to visualize and classify the outliers. The robustness of RPCR is demonstrated through simulations and the analysis of a real data set. Copyright © 2003 John Wiley & Sons, Ltd.
Kinetic modelling of acetic fermentation in an industrial process by genetic algorithms with a desirability function
Authors: Pizarro Consuelo , González‐Sáiz José M. , Garrido‐Vidal Diego
Published: January 2005

The basic tool to simulate the evolution of a bioprocess, such as the industrial process of acetic fermentation, is the kinetic model. The model must be simple and have a high predictive ability to give results capable of explaining the real behaviour. The difficulties in the kinetic modelling of biological processes are mainly related to the description of the bacterial growth. In this paper a genetic algorithm is designed to obtain a set of kinetic parameters for the specific growth rate that enables the model to explain the industrial fermentation. Only acetic concentration data from industrial fermentators are required. A four‐factor desirability function works properly as the response to maximize. The model optimized can explain not only the behaviour of the industrial batch process studied, but also the experimental results obtained with a pilot fermentator working continuously with and without cell recycling. Copyright © 2003 John Wiley & Sons, Ltd.
Analysis of combined mass‐ and volume‐transducing sensor arrays
Authors: Wise Barry M. , Gallagher Neal B. , Grate Jay W.
Published: January 2005

In prior work it was shown that both mass‐ and volume‐transducing sensor arrays with polymer coatings can be modeled with a classical least squares (CLS)‐type formulation. Given a response vector, this method allows one to solve simultaneously for the vapor descriptors and concentration, even for previously unseen analytes. It has also been shown that inverse least squares (ILS) models can be used in this system to estimate vapor descriptors. A more challenging task is to extract vapor descriptors from sensor arrays which respond to both mass and volume changes simultaneously. This problem is important because surface acoustic wave (SAW) sensors, and probably other types of sensors such as flexural plate wave (FPW) sensors, respond via both mass and volume mechanisms. In this work we show how a closed‐form solution can be obtained to a slightly simplified mass‐and volume‐sensitive system. This solution can be further refined with direct optimization using the full modeling equations. Simulations are performed to evaluate the accuracy of the approximate and refined solutions. This is compared with the accuracy of the known descriptors. Copyright © 2003 John Wiley & Sons, Ltd.
Characterizing batch reactions with in situ spectroscopic measurements, calorimetry and dynamic modeling
Authors: Ma Bei , Gemperline Paul J. , Cash Eric , Bosserman Mary , Comas Enric
Published: January 2005

A method for fully characterizing consecutive batch reactions using self‐modeling curve resolution of in situ spectroscopic measurements and reaction energy profiles is reported. Simultaneous measurement of reaction temperature, reactor jacket temperature, reactor heater power and UV/visible spectra was made with a laboratory (50 ml capacity) batch reactor equipped with a UV/visible spectrometer and a fiber optic attenuated total reflectance (ATR) probe. Composition profiles and pure component spectra of reactants and products were estimated without the aid of reference measurements or standards from the in situ UV/visible spectra using non‐negative alternating least squares (ALS), a type of self‐modeling curve resolution (SMCR). Multiway SMCR analysis of consecutive batches permitted standardless comparisons of consecutive batches to determine which batch produced more or less product and which batch proceeded faster or slower. Dynamic modeling of batch energy profiles permitted mathematical resolution of the reaction dose heat and reaction heat. Kinetic fitting of the in situ reaction spectra was used to determine reaction rate constants. These three complementary approaches permitted simple and rapid characterization of the reaction's rate of reaction, energy balance and mass balance. Copyright © 2003 John Wiley & Sons, Ltd.
Statistical process monitoring: basics and beyond
Authors: Joe Qin S.
Published: January 2005

This paper provides an overview and analysis of statistical process monitoring methods for fault detection, identification and reconstruction. Several fault detection indices in the literature are analyzed and unified. Fault reconstruction for both sensor and process faults is presented which extends the traditional missing value replacement method. Fault diagnosis methods that have appeared recently are reviewed. The reconstruction‐based approach and the contribution‐based approach are analyzed and compared with simulation and industrial examples. The complementary nature of the reconstruction‐ and contribution‐based approaches is highlighted. An industrial example of polyester film process monitoring is given to demonstrate the power of the contribution‐ and reconstruction‐based approaches in a hierarchical monitoring framework. Finally we demonstrate that the reconstruction‐based framework provides a convenient way for fault analysis, including fault detectability, reconstructability and identifiability conditions, resolving many theoretical issues in process monitoring. Additional topics are summarized at the end of the paper for future investigation. Copyright © 2003 John Wiley & Sons, Ltd.
Shifted factor analysis—Part II: Algorithms
Authors: Hong Sungjin , Harshman Richard A.
Published: January 2005

We previously proposed a family of models that deal with the problem of factor position shift in sequential data. We conjectured that the added information provided by fitting the shifts would make the model parameters identifiable, even for two‐way data. We now derive methods of parameter estimation and give the results of experiments with synthetic data. The alternating least squares (ALS) approach is not fully suitable for estimation, because factor position shifts destroy the multilinearity of the latent structure. Therefore an alternative ‘quasi‐ALS’ approach is developed, some of its practical and theoretical properties are dealt with and several versions of the quasi‐ALS algorithm are described in detail. These procedures are quite computation‐intensive, but analysis of synthetic data demonstrates that the algorithms can recover shifting latent factor structure and, in the situations tested, are robust against high error levels. The results of these experiments also provide strong empirical support for our conjecture that the two‐way shifted factor model has unique solutions in at least some circumstances. Copyright © 2003 John Wiley & Sons, Ltd.
Shifted factor analysis—Part III: N‐way generalization and application
Authors: Hong Sungjin , Harshman Richard A.
Published: January 2005

The ‘quasi‐ALS’ algorithm for shifted factor estimation is generalized to three‐way and n‐way models. We consider the case in which mode A is the only shifted sequential mode, mode B determines shifts, and modes above B simply reweight the factors. The algorithm is studied using error‐free and fallible synthetic data. In addition, a four‐way chromatographic data set previously analyzed by Bro et al. (J. Chemometrics 1999; 13: 295–309) is reanalyzed and (two or) three out of four factors are recovered. The reason for the incomplete success may be factor shape changes combined with the lack of distinct shift patterns for two of the factors. The shifted factor model is compared with Parafac2 from both theoretical and practical points of view. Copyright © 2003 John Wiley & Sons, Ltd.
Scatter plotting in multivariate data analysis
Authors: Geladi Paul , Manley Marena , Lestander Torbjörn
Published: January 2005

In data analysis, many situations arise where plotting and visualization are helpful or an absolute requirement for understanding. There are many techniques of plotting data/parameters/residuals. These have to be understood and visualization has to be made clearly and interpreted correctly. In this paper the classical favourites in chemometrics, scatter plots, are looked into more deeply and some criticism based on recent literature references is formulated for situations of principal component analysis, PARAFAC three‐way analysis and regression by partial least squares. Biplots are also afforded some attention. Examples from near‐infrared spectroscopy are given as illustrations. Copyright © 2003 John Wiley & Sons, Ltd.
Limits of detection in linear regression with errors in the concentration
Authors: del Río Bocio F. Javier , Riu Jordi , Boqué Ricard , Rius F. Xavier
Published: January 2005

This paper discusses a method for calculating the limit of detection in analytical methods in which the calibration stage takes into account the errors in both concentrations and instrumental responses. The proposed method considers the heteroscedastic individual errors on both axes, i.e. it uses the bivariate least squares (BLS) regression method. The expressions were applied to X‐ray fluorescence (XRF) and capillary electrophoresis (CE) determinations to calculate the limits of detection of nine elements in solid rocks and three anions in water respectively. The limits of detection with these expressions have been compared with those obtained with ordinary least squares (OLS) and weighted least squares (WLS). The results show that the limits of detection when the BLS procedure is used are smaller than when the other techniques are used. Copyright © 2003 John Wiley & Sons, Ltd.
Fiberoptic ductoscopy findings in women with and without spontaneous nipple discharge
Authors: Sauter Edward R. , Ehya Hormoz , Klein‐Szanto Andres J. P. , Wagner‐Mann Colette , MacGibbon Brenda
Published: January 2005

BACKGROUND

Fiberoptic ductoscopy (FD), which allows direct visualization of the breast ductal lumen, is performed in women with and without spontaneous nipple discharge (SND). Previous reports suggested that cytologic evaluation of SND may be falsely interpreted as containing malignancy. The purpose of the current study, which was performed prospectively, was to determine whether ductoscopic findings were different in women with versus without SND, and to assess the implications of the differences in SND versus non‐SND samples regarding the role of FD in assessing whether a woman has breast carcinoma.

METHODS

Data were collected on the distance traveled by the ductoscope, visual observations, pathology, cytology, epithelial and foam cell quantity, and image analysis for ploidy, hypertetraploidy, and S‐phase fraction.

RESULTS

Of 100 FD specimens, 60 were from breasts without SND and 40 were from breasts with SND. Intraductal visual observations (P ≤ 0.0002), pathologic findings in the resected specimen (P ≤ 0.001), and quantity of epithelial cells (P = 0.03) were influenced by the presence or absence of SND. Although one specimen from a benign breast was interpreted as cytologically malignant, every breast with both malignant cytology and aneuploidy contained cancer cells. A model incorporating cytology and SND was 92% sensitive and 60% specific in predicting which women had breast carcinoma.

CONCLUSIONS

There were pronounced differences in FD samples from women with and without SND. FD biologic parameters can be chosen to optimize breast carcinoma predictive sensitivity and specificity. SND cytology can present a diagnostic problem, suggesting the need for histologic confirmation before the initiation of therapy. Cancer 2005. © 2005 American Cancer Society.
Loss of E‐cadherin and p27 expression is associated with head and neck squamous tumorigenesis
Authors: Massarelli Erminia , Brown Erika , Tran Ngoc K. , Liu Diane D. , Izzo Julie G. , Lee J. Jack , El‐Naggar Adel K. , Hong Waun K. , Papadimitrakopoulou Vassiliki A.
Published: January 2005

BACKGROUND

In neoplastic head and neck lesions, it has been found that the loss or reduction in E‐cadherin expression is a late event and is associated with invasion. Low p27 levels have been associated with a poor prognosis in many different tumors, including laryngeal carcinoma. The authors investigated p27 and E‐cadherin protein expression in the early stages of head and neck tumorigenesis and evaluated their predictive roles individually and in association with carcinogenesis.

METHODS

Tissue biopsies from 46 patients who were participants in 3 chemoprevention trials were analyzed for E‐cadherin expression, and 40 samples were analyzed for p27 expression using immunohistochemistry.

RESULTS

The data suggested that loss of both E‐cadherin expression and p27 expression occurred early during the preneoplastic steps of head and neck carcinogenesis, and loss of p27 protein expression alone (P = 0.02) and in combination with loss of E‐cadherin expression (P = 0.04) was a significant predictor of the risk for head and neck carcinoma.

CONCLUSIONS

The loss of p27 expression may be useful in the construction of a risk model for head and neck carcinogenesis and may represent a potential target for chemopreventive interventions. Longer follow‐up of the high percentage of low‐risk preneoplastic lesions in the current study and validation in a larger sample size may be required to establish the predictive role of these abnormalities. Cancer 2005. © 2005 American Cancer Society.
Perspectives for the management of febrile neutropenic patients with cancer in the 21st century
Authors: Sipsas Nikolaos V. , Bodey Gerald P. , Kontoyiannis Dimitrios P.
Published: January 2005

Over the past several decades, there has been substantial progress in the management of patients with febrile neutropenia. However, the ever‐changing patterns of infection, ecology, and antibiotic‐resistance trends do not allow the development of treatment guidelines that could be applied universally. Hence, the institution's predominant pathogens and resistance patterns should guide the empirical choice of antimicrobials. Prompt initiation of antimicrobial therapy remains the gold standard. Monotherapy with the newer broad‐spectrum antimicrobials has tended to replace the classic combination therapy. Empirical administration of glycopeptides, such as vancomycin, without documentation of a gram‐positive infection is not favored. The development of risk‐stratification models has allowed for identification of low‐risk patients with additional treatment options, such as early discharge and exclusively outpatient treatment with oral antimicrobials. The initiation of empirical antifungal therapy in persistently febrile neutropenic patients has become common practice, especially recently, since the introduction of new, effective, less toxic antifungal drugs. It is hoped that the development of new nonculture‐based diagnostic methods will allow for the early detection of invasive fungal infections and, thus, the replacement of empirical antifungal therapy with pathogen‐specific, preemptive therapy. Cancer 2005. © 2005 American Cancer Society.
Combined chemotherapy with carmustine, doxorubicin, etoposide, vincristine, and cyclophosphamide plus mitoxantrone, cytarabine and methotrexate with citrovorum factor for the treatment of aggressive non‐Hodgkin lymphoma
Authors: Rigacci Luigi , Carrai Valentina , Nassi Luca , Alterini Renato , Longo Giovanni , Bernardi Franco , Bosi Alberto
Published: January 2005

BACKGROUND

The standard treatment for patients with aggressive non‐Hodgkin lymphoma (NHL) is cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). Since 1989, the authors have used a new chemotherapy regimen with combined carmustine, doxorubicin, etoposide, vincristine, and cyclophosphamide plus mitoxantrone, cytarabine and methotrexate with citrovorum factor called BAVEC‐MiMA. The objective of the current study was to explore, after a long follow‐up period, the impact of this third‐generation regimen for the treatment of aggressive NHL.

METHODS

One hundred and one consecutive patients (median age, 41 years) with either B‐cell (n = 94 patients) or non‐B‐cell (n = 7 patients), aggressive lymphoma were diagnosed and treated between 1989 and 1999 with the BAVEC‐MiMA regimen.

RESULTS

The complete response rate was 74%, and the overall response rate was 89%. Eleven patients with refractory disease died rapidly after a median period of 5 months. The major toxicity was Grade 4 neutropenia (according to World Health Organization criteria), which was observed in 15 patients (15%). There were four toxicity‐related deaths. The overall survival rate was 63% at 9 years. In multivariate analysis, factors that were associated with advantage in overall survival were response to induction therapy, bulky disease, and high score on the International Prognostic Index (IPI). The disease‐free survival rate was 77% at 9 years. In multivariate analysis, the IPI was the most important variable for the definition of disease‐free survival.

CONCLUSIONS

The BAVEC‐MiMA regimen was feasible on an outpatient basis, it was tolerated well, and it showed a low toxicity‐related mortality. The long follow‐up in patients with NHL, which is a rapidly fatal disease, led the authors to observe that, with this regimen, a cure was obtained in > 50% of patients who had low‐risk or low‐to‐intermediate‐risk, aggressive NHL. Cancer 2005. © 2005 American Cancer Society.
Is older age associated with a worse prognosis due to different patterns of care?
Authors: Lutterbach Johannes , Bartelt Susanne , Momm Felix , Becker Gerhild , Frommhold Hermann , Ostertag Christoph
Published: January 2005

BACKGROUND

The objective of this study was to find out whether the worse prognosis of older patients with primary or metastatic brain tumors can be explained by different patterns of care compared with younger patients.

METHODS

A data base that included 430 patients with glioblastomas and 916 patients with brain metastases who underwent radiotherapy at the author's hospital between 1980 and 2000 was analyzed. Patterns of care were compared for different age groups using the chi‐square test.

RESULTS

In both patient groups, age turned out to be an independent risk factor. Older age was associated with worse overall survival. Independent of the cut‐off age (< 50 years vs. ≥ 50 years, < 60 years vs. ≥ 60 years, < 65 years vs. ≥ 65 years, and < 70 years vs. ≥ 70 years), there were no statistically significant differences between the age groups concerning the use of different imaging modalities (computed tomography scans vs. magnetic resonance imaging), type of surgery (none vs. biopsy vs. resection), waiting time for radiotherapy (< median vs. ≥ median), radiotherapy treatment planning (simulator‐based vs. computer‐based), use of radiation sources (cobalt unit vs. linear accelerator), and fractionation protocols (conventional vs. modified). When the recruitment period of 21 years was divided into 3 intervals, impressive changes with regard to the patterns of care became apparent. However, the changes were seen similarly throughout the different age groups.

CONCLUSIONS

Older age did not limit access to state‐of‐the‐art patterns of care in neurooncology. Patients participated in medical progress irrespective of their age. The worse prognosis of older patients with glioblastomas or brain metastases was not determined by age‐related differences in access to health care. Cancer 2005. © 2005 American Cancer Society.
Gaussian radial basis functions and the approximation of input–output maps
Authors: Sandberg Irwin W.
Published: January 2005

Radial basis functions are of interest in connection with a variety of approximation problems in the neural networks area, and in other areas as well. Here we show that the members of some interesting families of shift‐varying input–output maps, that take a function space into a function space, can be uniformly approximated, over an infinite time or space domain, in a certain special way using Gaussian radial basis functions. Copyright © 2003 John Wiley & Sons, Ltd.
Analytical transient response of MOS current mirrors
Authors: Kayssi Ayman
Published: January 2005

The analytical transient response of MOS current mirrors is derived for the case when the input current is a saturating ramp. The closed form solution obtained for the voltages and currents in the circuit is expressed using Airy's functions. The settling time is then calculated using the closed‐form current equation. For the case when the settling time is greater than the transition time of the input current, a closed form solution is obtained. When the settling time is less than the input transition time, a very simple fitting function is found to accurately model the dependence of the settling time on the various parameters in the circuit, including the transition time of the input current. Simulations show excellent agreement of the estimates of the settling time macromodel with LEVEL‐1 SPICE results. For LEVEL‐3 MOSFET models, the error in the macromodel is within 20% of detailed circuit simulation. Copyright © 2003 John Wiley & Sons, Ltd.