bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of loud noise exposure on mouse myocardium: A comparison with the rat
Authors: Gesi Marco , Lenzi Paola , Fornai Francesco , Ferrucci Michela , Soldani Paola , Pellegrini Antonio , Paparelli Antonio
Published: October 2002

Loud noise is an environmental stressor of everyday life, which affects different organs and apparati, in particular the cardiovascular system. We have already reported that noise exposure produces significant alterations in the rat myocardium, consisting of mitochondrial damage, which is evident as lysis of the cristae and dilution of the matrix. Since there are high similarities between mouse and human species, the aim of our study was to investigate the effects of acute noise exposure on the mouse heart. We found that noise exposure affects mouse myocardium at similar subcellular sites to those already described in the rat; nonetheless, quantitative analysis of the percentage of altered mitochondria in both species disclosed a clear difference between mouse and rat myocardium, which strongly suggests a different sensitivity to noise stimulus. We hypothesize that the species differences on the extent of myocardial alterations here observed might be due to the zonal pattern of cardiac noradrenergic receptors, which should be the final effectors for noise‐induced myocardial changes. Microsc. Res. Tech. 59:131–135, 2002. © 2002 Wiley‐Liss, Inc.
Gas‐phase behaviour of negative ions produced from thiazidic diuretics under electrospray conditions
Authors: Garcia Patrice , Popot Marie Agnès , Fournier Françoise , Bonnaire Yves , Tabet Jean Claude
Published: October 2002

A systematic mass spectrometric study of 10 thiazidic diuretics and related compounds was undertaken by mass spectrometry (MS) with electrospray ionization in the negative ion mode. Collisional dissociation ‘in‐source’ (CID‐MS) and in a low‐pressure collision cell (CID‐MS/MS) were compared in both excitation regions. Spectra obtained by CID‐MS and by CID‐MS/MS were matched. Using the two methods, loss of HCl and consecutive dissociations from 2HCl losses were exhibited from compounds such as methyclothiazide and trichlormethiazide but not from other thiazidic diuretics that contain chlorine substituents in the aromatic moiety. However, deprotonated dichlorphenamide gave rise to loss of HCl by CID‐MS and CID‐MS/MS. For other diuretics such as hydroflumethiazide and hydrochlorothiazide, the loss of HCN and [HCN + SO2] was relevant. Reaction mechanisms were checked by means of deuterium–hydrogen exchange, which showed that deprotonation took place regioselectively on the heterocyclic moiety. The cleavage pathways require molecular isomerization forming ion–dipole complexes prior to decompositions, allowing long‐distance proton transfer for neutral elimination. Identifications of the most specific fragmentations presented in this paper were applied to the screening and unambiguous identification of diuretics for horse doping control. Copyright © 2002 John Wiley & Sons, Ltd.
Protein secondary structure and stability determined by combining exoproteolysis and matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry
Authors: Villanueva Josep , Villegas Virtudes , Querol Enrique , Avilés Francesc X. , Serrano Luis
Published: October 2002

In the post‐genomic era, several projects focused on the massive experimental resolution of the three‐dimensional structures of all the proteins of different organisms have been initiated. Simultaneously, significant progress has been made in the ab initio prediction of protein three‐dimensional structure. One of the keys to the success of such a prediction is the use of local information (i.e. secondary structure). Here we describe a new limited proteolysis methodology, based on the use of unspecific exoproteases coupled with matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry (MALDI‐TOF MS), to map quickly secondary structure elements of a protein from both ends, the N‐ and C‐termini. We show that the proteolytic patterns (mass spectra series) obtained can be interpreted in the light of the conformation and local stability of the analyzed proteins, a direct correlation being observed between the predicted and the experimentally derived protein secondary structure. Further, this methodology can be easily applied to check rapidly the folding state of a protein and characterize mutational effects on protein conformation and stability. Moreover, given global stability information, this methodology allows one to locate the protein regions of increased or decreased conformational stability. All of this can be done with a small fraction of the amount of protein required by most of the other methods for conformational analysis. Thus limited exoproteolysis, together with MALDI‐TOF MS, can be a useful tool to achieve quickly the elucidation of protein structure and stability. Copyright © 2002 John Wiley & Sons, Ltd.
Inhibition of insulin‐like growth factor I activity contributes to the premature apoptosis of cerebellar granule neuron in weaver mutant mice: In vitro analysis
Authors: Zhong Jin , Deng Jixian , Ghetti Bernardino , Lee Wei‐Hua
Published: October 2002

Evidence from transgenic mice and cultured cerebellar neurons supports an important role for insulin‐like growth factor I (IGF‐I) in the formation of cerebellar cytoarchitecture. To understand IGF‐I's function during cerebellar development, we examined the involvement of IGF‐I in the premature apoptosis of granule neurons derived from the cerebella of weaver (wv) mutant mice. Before their demise, wv granule neurons increased the expression and secretion of IGFBP5 in a gene dose‐dependent manner. Because IGFBP5 may interfere with the interaction of IGF‐I and its receptor, the abnormally high IGFBP5 levels in wv granule neurons suggest that a lack of IGF‐I activation may contribute to their premature apoptosis. This hypothesis is supported by a gene dose‐dependent decrease in IGF‐I receptor (IGF‐IR) phosphorylation. More importantly, there is a parallel gene dose‐dependent decrease in Akt activity, which was inversely correlated with the activity levels of caspase 3. On the other hand, adding IGFBP5 antibody into culture media increased the survival of wv granule neurons, whereas adding IGFBP5 decreased the survival of wild‐type granule neurons. To delineate the interaction between IGF‐I and IGFBP5 on wv granule neurons, we examined neuronal survival after treating with IGF‐I, des(1–3) IGF‐I, or IGFBP5 antibody. At the same concentration, des(1–3) IGF‐I was more effective than IGF‐I in promoting survival, in increasing Akt activity, and in decreasing caspase 3 activity. These results indicate that IGF‐I's actions on wv granule neurons are normally inhibited by excess IGFBP5, and sufficient IGF‐I receptor activation rescues wv granule neurons via stimulating the Akt signaling pathway. © 2002 Wiley‐Liss, Inc.
Interaction of 2‐mercaptoethanesulfonate monolayers on silver with sodium cations
Authors: Kudelski Andrzej , Pecul Magdalena , Bukowska Jolanta
Published: October 2002

Interactions of 2‐mercaptoethanesulfonate (MES) monolayers formed on silver surfaces with Na+ cations of the surrounding electrolytes were investigated by surface‐enhanced Raman scattering (SERS). The structures and wavenumbers of the MES anion and the anion–sodium cation ion pair were calculated at the SCF (self‐consistent field) level to facilitate assignment of the bands and for a better interpretation of the cation‐induced effects. The SERS results demonstrate that the interaction of sulfonic groups of immobilized MES molecules with sodium cations is significantly different to the respective interactions observed for ‘free’ MES molecules in aqueous solution. In the case of surface‐attached MES molecules, the contact ion pairs with metal cations are easily formed. The local symmetry of a large part of the sulfonic groups forming contact ion pairs with the metal cations is not lowered, in contrast to what one can observe in crystals of MES sodium salt and to what was predicted theoretically for an isolated MES molecule interacting with Na+. It is worth emphasizing that such interactions could significantly modify the structure of organic monolayer/electrolyte interface. Copyright © 2002 John Wiley & Sons, Ltd.
Vibrational spectra of YbBiGeO5
Authors: Baran Enrique J. , Cascales Concepción
Published: October 2002

The infrared and Raman spectra of YbBiGeO5 were recorded and are briefly discussed on the basis of its structural peculiarities. The infrared spectra of the complete series of isostructural LnBiGeO5 compounds (Ln = Dy–Lu and Y) were also recorded and some comparisons with related species are made. Copyright © 2002 John Wiley & Sons, Ltd.
Beyond competitive advantage
Authors: Klein Jeremy
Published: October 2002

While business strategy has become synonymous with the search for competitive advantage, the concept of competitive advantage is surprisingly confused.

Often the term is nothing more than a tautology. Successful firms are successful because they have competitive advantage, which in turn cannot be defined in any other way than as a quality that brings about success.

There is also ambiguity as to the locus of competition: whether competitive advantage is a property of firms or of products. This ambiguity creates confusion over the processes by which competition occurs.

Greater distinction and definitional clarity should be made between competition and strategy. Better strategies will result from more accurate pinpointing of the processes of competition, something that is unlikely while competition is simply seen in terms of competitive advantage.

Copyright © 2002 John Wiley & Sons, Ltd.
Accumulation of thiobarbituric acid‐reactive substances in cured pork sausages treated with propolis extracts
Authors: Han S K , Park H K
Published: October 2002

Propolis collected by bees has many components that possess antifungal, anticancer and antioxidant properties. Cured ground pork meat was treated separately with 0.4% w/w ethanol‐extracted propolis (EEP 0.4%), 0.6% w/w water‐extracted propolis (WEP 0.6%), 0.8% w/w dried residue of ethanol‐extracted propolis (DREEP 0.8%) and 0.1% w/w potassium sorbate (PS 0.1%) and made into sausages. Thiobarbituric acid‐reactive substances (TBARS) were measured in the sausages to assess the effects of storage at 5, 10 and 20 °C after 0, 2 and 4 weeks. After 4 weeks of storage at 5 °C the sausages treated with EEP 0.4%, DREEP 0.8%, WEP 0.6% and PS 0.1% yielded TBARS values which were 50, 59, 35 and 91% respectively of the control value. There was an increase of 0.33 mg MDA kg−1, the lowest of all treatments, in TBARS for the 0.4% w/w EEP‐treated sausages. The curing process will control microbiological spoilage, as will potassium sorbate.

© 2002 Society of Chemical Industry
Reduced growth of human sarcoma xenografts in hosts homozygous for the lit mutation
Authors: Deitel Kevin , Dantzer Dale , Ferguson Peter , Pollak Michael , Beamer Wes , Andrulis Irene , Bell Robert
Published: October 2002

Background and Objectives

Prior studies have shown that sarcoma growth can be stimulated by insulin‐like growth factor‐I (IGF‐I). To extend this line of research, we carried out in vivo growth studies of primary human sarcoma in immunosuppressed control and IGF‐I–deficient mice.

Methods

Human sarcoma specimens (one osteosarcoma and seven soft tissue sarcomas) were harvested in the operating room and implanted in immunosuppressed mice. Second‐generation sarcomas were transplanted to control (GH replete lit/+ mice) and to experimental (GH/IGF‐I–deficient lit/lit) animals. When tumors reached 1,000 mm3 in one group, average tumor size was compared in the two groups. IGF‐I receptor expression was measured by RT‐PCR and IGF‐I receptor binding sites were assayed by radiolabeled IGF‐I.

Results

Five of eight sarcomas demonstrated reduced growth in the GH/IGF‐I–deficient lit/lit animals. In four of the five sarcomas that demonstrated growth inhibition, IGF‐R was elevated relative to placenta or a positive control cell line (MCF‐7, which is known to be responsive to IGF‐I in vitro and in vivo). In three of the five sarcomas that demonstrated growth suppression, IGF‐R was elevated twofold after implantation in the experimental IGF‐I–deficient animals.

Conclusions

The GH–IGF axis may be an important stimulator of tumor growth in sarcomas. These experiments suggest that IGF suppression may inhibit sarcoma growth in vivo. J. Surg. Oncol. 2002;81:75–79. © 2002 Wiley‐Liss, Inc.
Posttraumatic tremor without parkinsonism in a patient with complete contralateral loss of the nigrostriatal pathway
Authors: Zijlmans Jan , Booij Jan , Valk Jaap , Lees Andrew , Horstink Martin
Published: October 2002

We present a patient with posttraumatic tremor who did not show any [123I]FP‐CIT uptake in the contralateral putamen and caudate. The absence of hypokinesia and rigidity is surprising in the presence of a striatal dopaminergic denervation that is even more severe than in Parkinson's disease. An explanation, therefore, could be that the lesion in the subthalamic nucleus in our patient prevented the onset of a Parkinson syndrome. © 2002 Movement Disorder Society
Stiff man syndrome and related conditions
Authors: Meinck Hans‐Michael , Thompson Philip D.
Published: October 2002

The stiff man syndrome (SMS) and its variants, focal SMS, stiff limb (or leg) syndrome (SLS), jerking SMS, and progressive encephalomyelitis with rigidity and myoclonus (PERM), appear to occur more frequently than hitherto thought. A characteristic ensemble of symptoms and signs allows a tentative clinical diagnosis. Supportive ancillary findings include (1) the demonstration of continuous muscle activity in trunk and proximal limb muscles despite attempted relaxation, (2) enhanced exteroceptive reflexes, and (3) antibodies to glutamic acid decarboxylase (GAD) in both serum and spinal fluid. Antibodies to GAD are not diagnostic or specific for SMS and the role of these autoantibodies in the pathogenesis of SMS/SLS/PERM is the subject of debate and difficult to reconcile on the basis of our present knowledge. Nevertheless, evidence is emerging to suggest that SMS/SLS/PERM are manifestations of an immune‐mediated chronic encephalomyelitis and immunomodulation is an effective therapeutic approach. © 2002 Movement Disorder Society
Bragg–Pippard formalism for bianisotropic particulate composites
Authors: Sherwin Joseph A. , Lakhtakia Akhlesh
Published: October 2002

Here the Bragg‐Pippard (BP) formalism is extended in order to homogenize linear bianisotropic‐in‐bianisotropic particulate composites, assuming the inclusion particles to be ellipsoidal. The BP formalism yields satisfactory results as the inclusion volume fraction f → 1, unlike the Maxwell Garnett (MG) formalism but like the Bruggeman formalism. However, the BP formalism is asymmetric with respect to the two component mediums in the same way as the MG formalism is, but the Bruggeman formalism can be symmetric. © 2002 Wiley Periodicals, Inc. Microwave Opt Technol Lett 33: 40–44, 2002; DOI 10.1002/mop.10225
Control of interactions between two dark solitons propagating in optical fiber exhibiting randomly varying birefringence
Authors: Li Hong , Wang D. N.
Published: October 2002

In fiber with randomly varying birefringence, the interactions between dark solitons in the same polarization channel and in two orthogonal polarization channels are investigated by the use of numerical simulations. The results obtained show that the interaction between dark solitons in the same polarization channel is weak, whereas in the two orthogonal polarization channels it is strong and leads to the soliton splitting and soliton propagation instability. The randomly varying birefringence enhances the interaction between dark solitons in two orthogonal polarization channels. A nonlinear gain can be used to suppress the interactions and stabilize dark soliton propagation. © 2002 Wiley Periodicals, Inc. Microwave Opt Technol Lett 33: 49–52, 2002; DOI 10.1002/mop.10228
Shorting‐post loaded microstrip antenna array formation for conical and broadside radiation pattern
Authors: Srinivasan Vijay , Fusco V. F.
Published: October 2002

In this paper an array of four shorting post loaded square microstrip antennas (SMSA) in a cross fashion yielding conical as well as broadside radiation pattern is presented. Each element of the array is loaded with two shorting posts. The elements when fed with equal amplitude and phase yield a conical beam. A linearly polarized (LP) broadside pattern is obtained when two elements of the array, along either of the axis is fed with equal amplitude but a phase difference of 180° while a circularly polarized (CP) broadside pattern is obtained when all the elements of the array are fed with a phase difference of 0° −90° −180° −270°. Experimental and simulated results are presented and are in agreement. © 2002 Wiley Periodicals, Inc. Microwave Opt Technol Lett 35: 97–99, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.10527
A hybrid DWDM system for CATV and 256‐QAM transport in the campus
Authors: Tsai Chieh‐Lung , Huang Tong‐Long , Lu Hai‐Han
Published: October 2002

In this paper, we propose and demonstrate a 4‐wavelength hybrid dense‐wavelength‐division‐multiplexing (DWDM) system for CATV and 256‐QAM transport over a 4‐km multimode fiber (MMF) in the campus. Good performances of carrier‐to‐noise ratio (CNR), composite second order (CSO) and composite triple beat (CTB) were obtained for CATV video signals; and low bit error rate (BER) had been achieved for 256‐QAM digital passband signals over a 4‐km MMF transport. This technique makes possible analog video transmission and gigabit Ethernet to the classrooms through the existed MMF in the campus. © 2002 Wiley Periodicals, Inc. Microwave Opt Technol Lett 35: 000–000, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.10533
Miniaturized microstrip open‐loop filters
Authors: Yu J. J. , Chew S. T. , Leong M. S. , Ooi B. L.
Published: October 2002

New microstrip slow‐wave bandpass filters using open‐loop resonator loaded with inter‐digital capacitive fingers is proposed. The filter features not only compact in size, but also exhibits spurious stop‐band rejection. Filters of this type with elliptic function and Chebyshev response are demonstrated. There is good agreement between experimental and full‐wave electromagnetic (EM) simulation results. © 2002 Wiley Periodicals, Inc. Microwave Opt Technol Lett 35: 157–159, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.10545
Multi‐frequency patch antenna design via the method of moment and genetic algorithm
Authors: Bilotti Filiberto , Castellana Francesco , Vegni Lucio
Published: October 2002

A combined Method of Moment (MoM)/Genetic Algorithm (GA) numerical procedure for multi‐frequency patch antenna design is presented in this paper. MoM is applied to analyse rectangular patches fed by a coaxial probe and suspended over a ground plane. The impedance matrix of such a mother structure is, then, manipulated by a GA optimisation procedure in order to detect the optimal patch shape matching the required frequency properties. GA adoption enables optimal shape detection among all the possible shapes allowed by the mother structure dimensions and discretization, without having to examine the whole shape set derived from the mother structure. In order to show the GA synthesis capabilities, a design example of a dual band patch is then presented. © 2002 Wiley Periodicals, Inc. Microwave Opt Technol Lett 35: 184–186, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.10551
A modified locally conformal FDTD for broadwall radiating slot in a finite wall thickness waveguide
Authors: Yu Zhang , Long Li , Changhong Liang
Published: October 2002

A modified locally conformal finite‐difference time‐domain method (MLC‐FDTD) is presented in this paper, which is used to analyze broadwall radiating slots in a finite wall thickness waveguide, including the longitudinal slot and the inclined slot. In this paper, we make a direct analysis of the bulletheaded slots using MLC‐FDTD, and give the transformation errors of two kinds of equivalent methods frequently employed in the engineering design; the equal‐area and the equal‐perimeter transformations from the squareheaded slot to bulletheaded slot. The results show that the equal‐area transformation is more accurate. © 2002 Wiley Periodicals, Inc. Microwave Opt Technol Lett 35: 198–201, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.10556
An improved conformal FDTD algorithm of modeling planar microwave structures
Authors: Zhong Xiaolong , Mei Kenneth K.
Published: October 2002

An improved conformal FDTD algorithm for microwave planar structure is presented in this paper. To achieve high‐level accuracy and universality, but still keep the efficiency of the FDTD method, improved locally conformal algorithm and non‐uniform orthogonal grids are employed to model the planar metal structures. All field components in destructed lattice are updated using locally conformal integral form of equations in order to achieve more accurate results. And with non‐uniform orthogonal grids, arbitrary‐shape metal strips can be modeled without generating a lot of unstructured meshes. In this algorithm, additional updating procedures for the fields in the destructed Yee lattice are no longer needed. The time marching procedures remain almost as simple as a uniform rectangular grids scheme. An oblique positioned microstrip stub structure is tested as an example to show the validity of this algorithm. © 2002 Wiley Periodicals, Inc. Microwave Opt Technol Lett 35: 219–224, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.10562
Interchannel crosstalk on the acousto‐optic tunable filter (AOTF) for network applications
Authors: Sobrinho C. S. , Lima J. L. S. , Sombra A. S. B.
Published: October 2002

In this paper, we present a study of the crosstalk level of an acousto‐optic tunable filter (AOTF) operating with ultrashort light pulses (2 ps). Initially, we consider the performance of the device, with several lengths, operating in the linear and nonlinear regime without loss. Given low pump power (P0 = 1 W), the crosstalk level (XL) of this device always increases with the length of the AOTF, for three different device configurations: the soliton regime, the dispersionless regime, and the linear regime. For shorter devices (L/10 < ξL < L), the soliton regime presents the lower XL. However, this behavior is reversed for longer devices, where the filter bandwidth is much shorter than the pulse bandwidth. For the dispersionless regime and low pump power, the device with length of ξL = L/10 presents the lowest XL. As one starts increasing the pump power, the XL is increases as a consequence of the increase of the switched pulse's bandwidth. One would expect that the presence of nonlinearity leads to the broadening of the pulse bandwidth associated with the self‐phase modulation and, consequently, with the increase of the XL. For high power (P0 = 9 W), the switched pulse is also presenting pulse break up. However, in the limit of high pump powers, all the devices present almost the same XL of around −1.5 dB. For the soliton regime, in all the devices there is a decrease of the XL for pump powers around 1 W, which is the energy of the fundamental soliton. For high pump powers, all devices present a second peak, where again a decrease of the XL is detected. For the ξL = L/10 device, the minimum is around 8 W. The increase of the pump power results in high‐order solitons and pulse compression; in this situation, the bandwidth of the pulse increases and we can extrapolate the bandwidth of the device, the XL as increases. The study of the effect of the XL on the AOTF, operating with ultra‐short optical solitons, provides possibilities for achieving high efficiency in ultrafast all‐optical signal processing, especially for optical switches, filters, and optical transistors. The acoustic‐optic tunable filter (AOTF) has attracted great attention in recent years, in part because it appears to be a suitable basis for multiwavelength optical cross‐connects. It is probably the only known tunable filter that is capable of selecting several wavelengths simultaneously. This capability can be used to construct a multiwavelength router. © 2002 Wiley Periodicals, Inc. Microwave Opt Technol Lett 35: 230–235, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.10565
Structure elucidation and conformational analysis of a fused cyclopentanopyrazolidinol
Authors: Tsoleridis Constantinos A. , Stephanidou‐Stephanatou Julia
Published: October 2002

From the reaction of 2‐acetylcyclopentanone with benzoylhydrazine, the cyclopentanopyrazole derivative 4 was obtained as the only product. The structural assignment of this compound and also of the hydroxypyrazoline 3, used as a model compound, was established by analysis of their NMR spectra (1H, 13C, COSY, NOESY, HETCOR and COLOC). Copyright © 2002 John Wiley & Sons, Ltd.
Solid‐state CP/MAS 13C NMR studies on conformational polymorphism in sertraline hydrochloride, an antidepressant drug
Authors: Novoselsky Artem , Glaser Robert
Published: October 2002

The C(2) isotropic chemical shift values in solid‐state CP/MAS 13C NMR spectra of conformational polymorphs Form I (δ 28.5) and III (δ 22.9) of (1S,4S)‐sertraline HCl (1) were correlated with a γ‐gauche effect resulting from the respective 162.6° antiperiplanar and 68.8° (+)‐synclinal C(2) C(1) N CH3 torsion angles as measured by X‐ray crystallography. The similarity of the solution‐state C(2) chemical shifts in CD2Cl2 (δ 22.8) and DMSO‐d6 (δ 23.4) with that for Form III (and other polymorphs having C(2) C(1) N CH3 (+)‐synclinal angles) strongly suggests that a conformational bias about the C(1) N bond exists for 1 in both solvents. This conclusion is supported by density functional theory B3LYP/6‐31G(d)‐calculated relative energies of C(1) N rotameric models: (kcal) 0.00 [73.8 °C(2) C(1) N CH3 torsion angle], 0.88 (168.7°), and 2.40 (−63.4°). A Boltzmann distribution of these conformations at 25 °C is estimated to be respectively (%) 80.3, 18.3, and 1.4. Copyright © 2002 John Wiley & Sons, Ltd.
Genomic imprinting and epigenetic reprogramming: Unearthing the garden of forking paths
Authors: Kierszenbaum Abraham L.
Published: October 2002

Genomic imprinting, an epigenetic form of gene regulation, determines the parent‐dependent gene expression of marked or imprinted genes during gametogenesis and embryonic development. Imprinting involves differential allele DNA methylation in one sex cell lineage but not in the other. Egg and sperm each contributes the same DNA sequences to the zygote but epigenetic imprinting of a subset of genes determines that only one of the parent alleles are expressed relative to the parental origin. Primordial germ cells inherit biallelically imprinted genes from maternal and paternal origin and erase their imprints to start de novo monoallelic imprinting during gametogenesis. Epigenetic paternalization is an ongoing process in the mitotically‐dividing spermatogonial stem cell and derived meiotically‐dividing spermatocyte progeny to endow sperm with imprinted alleles. Epigenetic maternalization is restricted to the oocyte growth phase of folliculogenesis and is unrelated to DNA replication since it takes place while the oocyte remains in the diplotene stage of meiotic prophase I. Sperm and oocyte genomic methylation patterns depend on the activity of DNA methyltransferases (Dnmt). A variant of Dnmt1, designated Dnmt1o, accumulates in oocyte nuclei during the follicular growth phase. Dnmt3L, an isoform of Dnmt3a and Dnmt3b, but lacking enzymatic activity, interacts with Dnmt2a and Dnmt3b and is required for spermatogenesis. In the mouse early zygote, the male pronucleus is demethylated within 4 h of fertilization. Global demethylation takes place gradually up to the morula stage. In the blastocyst, de novo methylation is reestablished in the inner cell mass but not in the trophectoderm. Both the significance of genomic imprinting and the severe developmental defects caused by disrupted Dnmt activity, point to a need for a better understanding of the causes of low cloning efficiency by somatic nuclear transfer to enucleated ovulated oocyte. Mol. Reprod. Dev. 63: 269–272, 2002. © 2002 Wiley‐Liss, Inc.
Nature's ingenuity: Bypassing the classical secretory route via apocrine secretion
Authors: Hermo Louis , Jacks Duncan
Published: October 2002

Although it has been suggested that epithelial cells of the male reproductive system are involved in apocrine secretion, this method of secretion is not fully understood. In the present study, apocrine secretion was investigated in epithelial principal cells lining the epididymis and vas deferens (VD) of adult mice. The tissues were fixed by cardiac vascular perfusion with glutaraldehyde for routine electron microscope (EM) analysis and Bouin's fixative for light microscope (LM) immunocytochemistry to access functional roles. In the epididymis and VD, the apex of principal cells revealed protrusions of cytoplasm referred to as apical blebs (ABs). The latter contained solely numerous free ribosomes, 20 nm vesicles and few ER cisternae, suggesting segregation of their contents. While some ABs displayed wide areas of contact with the apical principal cell cytoplasm, others showed thin stalk‐like attachment points as well as fissures at the junction of the two areas. Together with images of ABs and their contents deep in the lumen, it is suggested that ABs detach from principal cells whereupon they breakdown to release their contents therein. As ABs of the epididymis were immunoreactive for glutathione‐S‐transferases (GSTs) and ubiquitin, it is proposed that these proteins are synthesized on free ribosomes in ABs and that apocrine secretion represents the manner whereby they enter the lumen to effectively protect sperm from free radical injury and ubiquitinate proteins for degradation, respectively. ABs of the VD were immunoreactive for 3β‐HSD, suggesting that they are also capable of synthesis of steroids with their release via apocrine secretion. Taken together the data provide evidence for apocrine secretion in the adult mouse epididymis and VD that could play important roles in relation to sperm maturation, protection and viability. Mol. Reprod. Dev. 63: 394–410, 2002. © 2002 Wiley‐Liss, Inc.
Biochemical correlates of thiazolidinedione‐induced adipocyte differentiation by high‐resolution magic angle spinning NMR spectroscopy
Authors: Chen Jin‐Hong , Enloe Brian M. , Weybright Patrick , Campbell Natalee , Dorfman David , Fletcher Christopher D. , Cory D.G. , Singer Samuel
Published: October 2002

Thiazolidinediones, a class of synthetic ligands to the peroxisome proliferator‐activated receptor‐γ, induce terminal adipocyte differentiation of 3T3 F442A cells, and have already been used as alternative therapeutic agents for the treatment of liposarcoma in clinical trials. The biochemical changes occurring in the 3T3 F442A cell line and well‐differentiated liposarcoma following induction of adipocyte differentiation with the thiazolidinedione troglitazone were measured using high‐resolution magic angle spinning (MAS) nuclear magnetic resonance (NMR) spectroscopy. 3T3 F442A cell differentiation was characterized by a large accumulation of intracellular triglyceride and withdrawal from the cell cycle. Phosphatidylcholine (PTC), phosphocholine (PC), myo‐inositol, and glycerol were found to be possible biochemical markers for adipocyte differentiation induced by thiazolidenediones. The molar ratio of PTC to PC increased fourfold in differentiated 3T3 F442A cells compared to undifferentiated cells, suggesting a substantial increase in CTP:phosphocholine cytidylyltransferase activity with differentiation. A 2.8‐fold increase in the PTC:PC ratio was observed in the lipoma‐like well‐differentiated liposarcoma of three patients who were treated with troglitazone when compared to liposarcoma from patients not treated with this drug. Thus, this ratio may be an NMR‐detectable marker of troglitazone efficacy and response to differentiation therapy for liposarcoma. Magn Reson Med 48:602–610, 2002. © 2002 Wiley‐Liss, Inc.
Induction of electric fields due to gradient switching: A numerical approach
Authors: Brand Martin , Heid Oliver
Published: October 2002

Since the first observations of peripheral nerve stimulation in MRI, it has been clear that the underlying mechanism is the activation of the nervous system by induced electric fields. However, compared to experimental investigations little work has been done on calculating these electric fields with adequate accuracy. In this article a numerical analysis of the electric fields induced by a complete whole body gradient system is presented. The calculations were carried out on three human body models of different complexities. The numerical results correlate better to the experimental observations with a body model that resembles the human body. Applying a model with inhomogeneous conductivity, numerical stability was not reached. The results were compared to the limits given in the upcoming IEC 60601‐2‐33 standard. The comparison shows that the derived peak electric fields depend substantially on the body model used, which dictates that limits have to refer to a body model that is exactly defined. Magn Reson Med 48:731–734, 2002. © 2002 Wiley‐Liss, Inc.
Interaction of high concentrations of riluzole with recombinant skeletal muscle sodium channels and adult‐type nicotinic receptor channels
Authors: Mohammadi Bahram , Lang Nicolas , Dengler Reinhard , Bufler Johannes
Published: October 2002

Riluzole is a neuroprotective drug that modulates glutamergic transmission but also blocks the inactivated state of voltage‐gated neuronal sodium channels at very low concentrations (about 0.1 μM). After nausea, the most common adverse effect of riluzole is asthenia, which could be due to a block of muscle sodium channels or acetylcholine receptor channels. Using the patch‐clamp technique, we applied riluzole on recombinant voltage‐gated skeletal muscle sodium and adult nicotinic acetylcholine receptor channels expressed in a mammalian cell line (HEK 293). Riluzole blocked the inactivated state of voltage‐gated skeletal muscle sodium channels, shifting the midpoint of the steady‐state inactivation curve to more negative potentials, but only in comparatively high concentrations (≥ 0.1 mM). At these concentrations, riluzole also caused an open‐channel block at acetylcholine receptor channels. We conclude that riluzole has only a mild blocking effect on the inactivated state of voltage‐gated skeletal muscle sodium channels and nicotinic acetylcholine receptor channels. As the plasma concentration of riluzole in amyotrophic lateral sclerosis (ALS) patients approximates 2 μM, it seems unlikely that asthenia is caused by a block of skeletal muscle sodium channels or acetylcholine receptor channels by riluzole. © 2002 Wiley Periodicals, Inc. Muscle Nerve 26: 539–545, 2002
Microdialysis and electromyography of experimental muscle fatigue in healthy volunteers and patients with mitochondrial myopathy
Authors: Axelson Hans W. , Melberg Atle , Ronquist Gunnar , Askmark Håkan
Published: October 2002

Consecutive 60‐min microdialysis samples were taken from the tibial anterior muscle in 11 healthy subjects and 4 patients with mitochondrial myopathy before (2–3 samples) and after (3–4 samples, 2 controls and 1 patient excluded) sustained isometric foot dorsiflexions. Before exercise, mean concentrations of lactate, pyruvate, hypoxanthine, urate, aspartate, and glutamate did not significantly differ between controls and patients. After exercise, the controls showed significantly increased concentrations of lactate, pyruvate, and urate, decreased hypoxanthine, and no change in aspartate and glutamate. Similar findings were observed in the patients. Plasma lactate was unchanged. Exercise‐induced increase in integrated electromyogram amplitude and rated subjective fatigue were correlated to increased post‐exercise lactate concentrations, with no obvious difference between the groups. Microdialysis of skeletal muscle allows the detection and monitoring of biochemical changes in the interstitial space. With the exercise protocol used, however, it was not possible to demonstrate any biochemical difference between healthy controls and patients with mitochondrial myopathy. © 2002 Wiley Periodicals, Inc. Muscle Nerve 26:520‐526, 2002
Markovian models of three‐on‐one combat involving a hidden defender
Authors: McNaught Ken R.
Published: October 2002

In this paper, Markovian models of three‐on‐one stochastic firefights between ground‐based weapon systems are developed. These models address a common scenario of interest to the military, but one which has been much neglected in analytic combat models, that of combat between a hidden defender and an exposed attacking force. Each combatant must detect an opponent before commencing their firing cycle, a task which is considerably more difficult for the attacker. In the models developed here, the defender detects the exposed attacking group after an exponentially distributed time interval, while each attacker has a fixed probability of detecting the defender via the flash signature produced after each shot fired by him. The utility of the approach is demonstrated by investigating what impact the introduction of a coordinated gun‐laying system for the attacking force might have, a system made possible by battlefield digitization. The method used here allows models to be developed incrementally. This and other advantages of the Markovian approach are discussed. © 2002 Wiley Periodicals, Inc. Naval Research Logistics 49: 627–646, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/nav.10041
13C‐NMR isotopomer distribution analysis: a method for measuring metabolic fluxes in condensation biosynthesis
Authors: Puccetti Caterina , Aureli Tommaso , Manetti Cesare , Conti Filippo
Published: October 2002

13C NMR spectroscopy associated with the use of 13C‐enriched substrates is a powerful tool to investigate intracellular metabolism because of the wealth of information contained in the distribution of isotopes in key metabolites. A new method of using 13C label distribution measurements in carbon skeletons of metabolites to estimate metabolic fluxes through biochemical reaction networks is presented here. This method can be applied to metabolite synthesis occurring by condensation reactions of the type nA → B, where n is the number of precursor A molecules needed to synthesize one molecule of product B. NMR isotopomer distribution analysis (NMR‐IDA) involves the introduction of a 13C‐enriched precursor, and measurements of the 13C positional enrichments at just one carbon atom position of the product B via 13C NMR spectroscopy. Information on isotopomer distribution is obtained, and data are analyzed according to a mathematical model based on multinomial probability expressions to obtain the best fit between theoretical and experimental 13C label distribution. The use of the NMR‐IDA method allows for estimation of two key parameters representing the fractional flux of 13C‐enriched tracer A molecules to total precursor A pool and the fraction of product B synthesized in the presence of a 13C‐enriched source, respectively. A practical example of NMR‐IDA application to fatty acid synthesis from [(1,2 13C2)acetyl]‐L‐carnitine in cultured primary astrocytes is also presented. Copyright © 2002 John Wiley & Sons, Ltd.
Minimax problems with bitonic matrices
Authors: Hochbaum Dorit S. , Tucker Paul A.
Published: October 2002

The minimax problem is a new optimization problem which substitutes maximum for addition in the constraint inequalities of a linear program. We show how a problem with n variables and m constraints can be reduced to a set cover problem with nm variables and m constraints. We define the mountain property on the coefficients in each column of the constraint matrix of a minimax problem and its generalization—the bitonic property. It is shown that these are equivalent, respectively, to set cover problems with consecutive 1's in each column or circular 1's in each column thus solving the periodic scheduling problem. We present a shortest path algorithm to solve a minimax problem with the mountain property in time O(mn + log m). For bitonic matrix problems, we present an algorithm of complexity O(m2(n + log n)). The same algorithms are used to solve a set cover problem on v sets and r elements to be covered in O(v + r log r) for a problem with consecutive 1's in each column and in O(v(v + r log r)) for a problem with circular 1's in each column. We further establish that r is at least \documentclass{article}\pagestyle{empty} \begin{document}$\Omega(\sqrt{v})$\end{document} and at most O(v). We also provide an efficient algorithm for recognizing bitonic matrices in O(mn log m) time. © 2002 Wiley Periodicals, Inc.
Intraneuronal amyloid precursor protein (APP) and appearance of extracellular β‐amyloid peptide (aβ) in the brain of aging kokanee salmon
Authors: Maldonado Tammy A. , Jones Richard E. , Norris David O.
Published: October 2002

Antibodies to human amyloid precursor protein (APP695) and beta‐amyloid peptide (Aβ1‐42) were used to determine timing of amyloidosis in the brain of kokanee salmon (Oncorhynchus nerka kennerlyi) in one of four reproductive stages: immature (IM), maturing (MA), sexually mature (SM), and spawning (SP), representing a range of aging from somatically mature but sexually immature to spawning and somatic senescence. In IM fish, immunoreactive (ir) intracellular APP occurred in 18 of 23 brain regions. During sexual maturation and aging, the number of neurons expressing APP increased in 11 of these APP‐ir regions. Aβ‐ir was absent in IM fish, present in seven regions in MA fish, moderately abundant in 15 regions in SM fish, and was most abundant in all brain regions of SP fish exhibiting Aβ‐ir. Intracellular APP‐ir was observed in brain regions involved in sensory integration, olfaction, vision, stress responses, reproduction, and coordination. Intra‐ and extracellular Aβ1‐42 immunoreactivity (Aβ‐ir) was present in all APP‐ir regions except the nucleus lateralis tuberis (hypothalamus) and Purkinje cells (cerebellum). APP‐ir and Aβ deposition increase during aging. APP‐ir is present in IM fish; Aβ‐ir usually appears first in MA or SM fish and increases in SM fish as does APP‐ir. Extracellular Aβ deposition dramatically increases between SM and SP stages (1–2 weeks) in all fish, indicating an extremely rapid and synchronized process. Rapid senescence observed in pacific salmon could make them a useful model to investigate timing of amyloidosis and neurodegeneration during brain aging. © 2002 Wiley Periodicals, Inc. J Neurobiol 53: 11–20, 2002
Postsynaptic kinase signaling underlies inhibitory synaptic plasticity in the lateral superior olive
Authors: Kotak Vibhakar C. , Sanes Dan H.
Published: October 2002

In the auditory system, inhibitory transmission from the medial nucleus of the trapezoid body (MNTB) to neurons of the lateral superior olivary nucleus (LSO) undergoes activity‐dependent long‐term depression, and may be associated with developmental elimination of these synapses [Sanes DH, Friauf E (2000). Review: development and influence of inhibition in the laterial superior olivary nucleus. Hear Res 147:46–58]. Although GABAB receptor activation and postsynaptic free calcium are implicated in this depression, little is known about intracellular signaling mechanisms in this or other forms of inhibitory plasticity. In this study, we asked whether the calcium dependency of inhibitory depression was associated with the activation of calcium/calmodulin‐dependent protein kinase II (CaMKII), protein kinase C (PKC), and/or cAMP‐dependent protein kinase A (PKA). Whole‐cell voltage‐clamp recordings were obtained from LSO neurons in a brain slice preparation, permitting for the selective pharmacologic manipulation of individual postsynaptic LSO neurons. Inclusion of a CaMKII antagonist (KN‐62) in the internal pipet solution blocked inhibitory synaptic depression. A second CaMKII inhibitor (autocamtide peptide fragment) significantly decreased inhibitory depression. Inclusion of a specific antagonist of protein kinase C (PKC fragment 19–36) in the internal recording solution also blocked inhibitory depression. To test involvement of a cAMP‐dependent intracellular cascade, two different manipulations were performed. Inclusion of PKA antagonists (Rp‐cAMPS or a cAMP dependent protein kinase inhibitor peptide) prevented inhibitory depression. In contrast, when a nonhydrolyzable cAMP analog (Sp‐cAMPS) was permitted to enter the postsynaptic cell, the MNTB‐evoked IPSCs became depressed in the absence of low‐frequency stimulation. Thus, three key postsynaptic kinases, CaMKII, PKC, and PKA, participate in the activity‐dependent depression of inhibitory MNTB‐LSO synapses during postnatal development. © 2002 Wiley Periodicals, Inc. J Neurobiol 53: 36–43, 2002
A component decomposition preconditioning for 3D stress analysis problems
Authors: Mihajlović M. D. , Mijalković S.
Published: October 2002

A preconditioning methodology for an iterative solution of discrete stress analysis problems based on a space decomposition and subspace correction framework is analysed in this paper. The principle idea of our approach is a decomposition of a global discrete system into the series of subproblems each of which correspond to the different Cartesian co‐ordinates of the solution (displacement) vector. This enables us to treat the matrix subproblems in a segregated way. A host of well‐established scalar solvers can be employed for the solution of subproblems. In this paper we constrain ourselves to an approximate solution using the scalar algebraic multigrid (AMG) solver, while the subspace correction is performed either in block diagonal (Jacobi) or block lower triangular (Gauss–Seidel) fashion. The preconditioning methodology is justified theoretically for the case of the block‐diagonal preconditioner using Korn's inequality for estimating the ratio between the extremal eigenvalues of a preconditioned matrix. The effectiveness of the AMG‐based preconditioner is tested on stress analysis 3D model problems that arise in microfabrication technology. The numerical results, which are in accordance with theoretical predictions, clearly demonstrate the superiority of a component decomposition AMG preconditioner over the standard ILU preconditioner, even for the problems with a relatively small number of degrees of freedom. Copyright © 2002 John Wiley & Sons, Ltd.