bluuebunny/crossref_metadata_2025 huggingface dataset:
Heat Treatment Induces Liver Receptor Homolog-1 Expression in Monkey and Rat Sertoli Cells
Authors: Guo Jian , Tao Shi-Xin , Chen Min , Shi Yu-Qiang , Zhang Zhu-Qiang , Li Yin-Chuan , Zhang Xue-Sen , Hu Zhao-Yuan , Liu Yi-Xun
Published: December 2006

We demonstrated in this study that liver receptor homolog-1 (LRH-1) was expressed in the round spermatids in normal monkey testis, and no LRH-1 signal was observed in the Sertoli cells. After local warming (43 C) the monkey testis, however, LRH-1 expression was induced in the Sertoli cells in coincidence with activation of cytokeratin 18 (CK-18), a Sertoli cell dedifferentiated marker. Furthermore, we isolated rat primary Sertoli cells from testes at various stages of development and treated with 43 C water in vitro. The changes in LRH-1 as well as CK-18 expression were analyzed by confocal immunohistochemistry and Western blot. The results showed that LRH-1 was stage-dependently expressed in the Sertoli cells; no LRH-1-positive signal was detected in the cells obtained from the testes of adult rat on d 60 after birth when mature spermatozoa in the testis was completed. However, the mature Sertoli cells were warmed at the 43 C water bath for 15 min, and the LRH-1 signal was remarkably induced in a time-dependent manner, just like the changes of CK-18 expression in the Sertoli cells, suggesting that the heat-induced dedifferentiation of the mature Sertoli cells might be related to LRH-1 regulation. LRH-1 expression induced by the heat treatment was completely inhibited by the addition of ERK inhibitor U0126 in the culture, indicating that the heat-induced LRH-1 expression in the Sertoli cells may be regulated via ERK1/2 activation pathway. Testosterone was found to have no such effect on LRH-1 expression in the monkey and rat Sertoli cells.
Limit theorems for a diffusion process with a one-sided Brownian potential
Authors: Kawazu Kiyoshi , Suzuki Yuki
Published: December 2006

We consider a diffusion process X(t) with a one-sided Brownian potential starting from the origin. The limiting behavior of the process as time goes to infinity is studied. For each t > 0, the sample space describing the random potential is divided into two parts, Ãt and B̃t, both having probability ½, in such a way that our diffusion process X(t) exhibits quite different limiting behavior depending on whether it is conditioned on Ãt or on B̃t (t → ∞). The asymptotic behavior of the maximum process of X(t) is also investigated. Our results improve those of Kawazu, Suzuki, and Tanaka (2001).
Extinction of branching symmetric α-stable processes
Authors: Shiozawa Yuichi
Published: December 2006

We give a criterion for extinction or local extinction of branching symmetric α-stable processes in terms of the principal eigenvalue for time-changed processes of symmetric α-stable processes. Here the branching rate and the branching mechanism are spatially dependent. In particular, the branching rate is allowed to be singular with respect to the Lebesgue measure. We apply this criterion to some branching processes.
A monotonicity result for a G/GI/c queue with balking or reneging
Authors: Ziya Serhan , Ayhan Hayriye , Foley Robert D. , Peköz Erol
Published: December 2006

In a G/GI/c loss system with balking, reneging, or limited waiting space, deleting some of the arriving customers can either increase or decrease the fraction of the remaining arrivals who get served, depending on how customers are deleted. We present a model in which the random deletion of arrivals independently and with some fixed probability can never decrease the fraction of the remaining arrivals who get served.
Transferrin and Apolipoprotein C-III Isofocusing Are Complementary in the Diagnosis of N- and O-Glycan Biosynthesis Defects
Authors: Wopereis Suzan , Grünewald Stephanie , Huijben Karin MLC , Morava Éva , Mollicone Rosella , van Engelen Baziel GM , Lefeber Dirk J , Wevers Ron A
Published: December 2006

Background: Apolipoprotein C-III (apoC-III) isoelectric focusing (IEF) can be used to detect abnormalities in the biosynthesis of core 1 mucin-type O-glycans.

Methods: We studied plasma samples from 55 patients with various primary defects in N- and/or O-glycosylation, 21 patients with secondary N-glycosylation defects, and 6 patients with possible glycosylation abnormalities. Furthermore, we analyzed 500 plasma samples that were sent to our laboratory for selective screening for inborn errors of metabolism.

Results: Plasma samples from patients with congenital disorders of glycosylation (CDG) types –IIe and –IIf showed a hypoglycosylated apoC-III isoform profile, as did plasma samples from 75% of the patients with an unspecified CDG type II. Hyposialylated O-glycan profiles were also seen in plasma from 2 patients with hemolytic-uremic syndrome. In the 500 plasma samples from the selective screening, 3 patients were identified with a possible isolated defect in the biosynthesis of core 1 mucin-type O-glycans.

Conclusions: To our knowledge this is the first study in which use of a plasma marker protein has identified patients in whom only O-glycan biosynthesis might be affected. The primary defect(s) remain as yet unknown. Plasma apoC-III IEF is complementary to transferrin isofocusing. In conjunction both tests identify biosynthesis defects in N-glycan and mucin-type core 1 O-glycan biosynthesis. The apoC-III IEF assay is likely to help metabolic laboratories to identify and unravel further subtypes of inborn errors of glycan biosynthesis.
Microsatellite Markers within —SEA Breakpoints for Prenatal Diagnosis of HbBarts Hydrops Fetalis
Authors: Ho Sherry Sze Yee , Chong Samuel S , Koay Evelyn SC , Chan Yiong Huak , Sukumar Ponnusamy , Chiu Lily-Lily , Wang Wen , Roy Ashim , Rauff Mary , Su Lin Lin , Biswas Arijit , Choolani Mahesh
Published: December 2006

Background: We sought to develop a rapid prenatal diagnostic test for simultaneous detection of HbBarts hydrops fetalis and exclusion of maternal contamination.

Methods: We developed a multiplex quantitative fluorescent PCR (QF-PCR) test that detects the presence/ absence of 2 microsatellite markers (16PTEL05/16PTEL06) located within breakpoints of the Southeast Asia (—SEA) deletion. HbBarts hydrops fetalis (—SEA/—SEA) is diagnosed by absence of both markers, and maternal contamination of fetal DNA is excluded by absence of noninherited maternal alleles. Fetal and parental DNA samples from 50 families were analyzed in a blinded clinical validation study, and QF-PCR results were compared with their respective molecular genotypes.

Results: The multiplex QF-PCR results included correct diagnoses of HbBarts hydrops fetalis in 11 of the fetuses tested, correct verification as unaffected in 20 fetuses, and correct identification as either carriers (αα/—SEA) or unaffected homozygotes in 18. Misidentification as unaffected occurred for 1 carrier. Sensitivity for diagnosis of HbBarts hydrops fetalis was 100% [lower 95% confidence interval, 76.2%], and specificity was 100% (lower 95% confidence interval, 92.6%). None of the samples tested showed any traces of noninherited maternal alleles; thus false-positives because of maternal contamination were eliminated.

Conclusions: In this QF-PCR method, detection of maternally and paternally inherited fetal alleles allowed diagnosis of the double-deletion syndrome, and the ability to differentiate between these alleles allowed simultaneous exclusion of maternal contamination of the fetal genetic material. This novel strategy using cell-free fetal DNA in maternal plasma could form the basis for noninvasive testing for HbBarts hydrops fetalis.
Towards a typology of discontinuous past marking
Authors: Plungian Vladimir A. , van der Auwera Johan
Published: December 2006

The paper discusses verbal markers of the past tense with a meaning roughly charac-terizable as “past and not present” or “past with no present relevance”. This type of past time reference (labelled “discontinuous”) is opposed to standard past markers, which normally do not provide any information about the state of affairs in the present domain. Discontinuous past can be analyzed as a special cross-linguistically valid type of past tense marking. It occurs in a considerable amount of genetically unrelated languages of different areas (especially in Oceania and West Africa), though in cur-rent descriptions it may sometimes hide behind misleading terms or fall under the broad headings of “past” or “anterior”.
Inducible and Reversible Transgene Expression in Human Stem Cells After Efficient and Stable Gene Transfer
Authors: Zhou Betty Ying , Ye Zhaohui , Chen Guibin , Gao Zhigang Peter , Zhang Yu A. , Cheng Linzhao
Published: December 2006

We report here a lentiviral vector system for regulated transgene expression. We used the tetracycline repressor fused with a transcriptional suppression domain (tTS) to specifically suppress transgene expression. Human cells were first transduced with a tTS-expressing vector and subsequently transduced with a second lentiviral vector-containing transgene controlled by a regular promoter adjacent to a high-affinity tTS-binding site (tetO). After optimizing the location of the tetO site in the latter vector, we achieved a better inducible transgene expression than the previous lentiviral vectors using the tetracycline repressor systems. In this new system, the transgene transcription from a cellular promoter such as EF1α or ubiquitin-C promoter is suppressed by the tTS bound to the nearby tetO site. In the presence of the tetracycline analog doxycycline (Dox), however, the tTS binding is released from the transgene vector and transcription from the promoter is restored. Thus, this system simply adds an extra level of regulation, suitable for any types of promoters (ubiquitous or cell-specific). We tested this tTS-suppressive, Dox-inducible system in 293T cells, human multipotent hematopoietic progenitor cells, and three human embryonic stem cell lines, using a dual-gene vector containing the green fluorescent protein reporter or a cellular gene. We observed a tight suppression in the uninduced state. However, the suppression is reversible, and transgene expression was restored at 5 ng/ml Dox. The lentiviral vectors containing the tTS-suppressive, Dox-inducible system offer a universal, inducible, and reversible transgene expression system in essentially any mammalian cell types, including human embryonic stem cells.
Scaling up of ecological sanitation for peri-urban and rural areas to meet the sanitation of MDGs
Authors: Harada H. , Matsui S. , Wakamatsu M.
Published: December 2006

Sanitizing human excreta with nutrient recovery is a crucial issue especially for peri-urban and rural areas of developing countries. In addition to human excreta, the sanitary concerns of livestock excreta are recently growing due to control the domestic-animal-related diseases such as bird flu. In order to address those problems, this study examines the vacuum truck-collection system combined with urine-faeces diversion for peri-urban and rural areas. In the system, the diverted faeces and livestock excreta are fermented, and urine is directly used and/or phosphorus in urine is recovered by struvite formation. Firstly, each treatment and recovery is examined from the technological aspects. Secondly, the methane and struvite production in the system is calculated. As a result, the fermentation was considered to proceeds easily compared to traditional mixed excreta fermentations, and nutrient in urine could be easily recovered in the system. In addition, the system produces methane of 1,107 Nm3-CH4 per day, struvite of 51.9 ton-P2O5 per year for a population of 100,000 with 5,000 pigs and 20,000 chickens.
Progression of mycosis of the auditory tube diverticulum (guttural pouch) after arterial occlusion in a horse with contralateral temporohyoid osteoarthropathy
Authors: Ernst Nicolas S. , Freeman David E. , MacKay Robert J.
Published: December 2006

Case Description—A 6-year-old Appaloosa mare was examined because of inappetance, difficulty eating, and swelling and mucopurulent discharge in the right eye.

Clinical Findings—Results of a CBC and serum bio-chemical analysis revealed no important findings. Ophthalmologic examination revealed scarring and ulcer-ation of the superficial layers of the cornea. Endoscopic examination of the upper portion of the respiratory tract and auditory tube diverticula (guttural pouches) revealed abnormal thickness of the right stylohyoid bone and a plaque suggestive of mycotic growth on the left internal carotid artery. Radiographic examination revealed right-sided otitis media. Temporohyoid osteoarthropathy in the right guttural pouch and mycosis in the left guttural pouch were diagnosed.

Treatment and Outcome—Ceratohyoidectomy of the right stylohyoid bone was performed, and the left internal carotid artery was occluded via placement of stainless steel spring embolization coils. The mare regained the ability to eat without difficulty and improved clinically for approximately 4 weeks. However, the mare returned to the medical center 53 days after surgery with left-sided Horner syndrome, atrophy of the right side of the tongue, and a 3-week history of dysphagia and weight loss. Endoscopic evaluation revealed progression of mycotic growth in the left guttural pouch. The mare was euthanatized.

Clinical Relevance—Although the mycotic lesion in the left guttural pouch was an incidental finding at the time of initial examination, the lesion progressed to cause dysphagia and Horner syndrome after occlusion of the left internal carotid artery, a treatment that is typically associated with resolution of guttural pouch mycosis. Arterial occlusion is not necessarily a reliable method of resolving guttural pouch mycosis.
Teach Me, but: Don't Disagree with Me
Authors: Fisler Jodi , Foubert John D.
Published: December 2006

Polarized politics is combining with the black-and-white thinking that prevails among many traditional-age college students and the often strong opinions of educators to produce a climate of frustration and discord on some American college campuses. What can be done to create a respectful environment where students feel their perspectives will be heard?
On Shaky Ground
Authors: Mueller Alan C. R.
Published: December 2006

Language, courage, and discussions of faith
Emanation and Generation
Authors: Mitchell Randy L.
Published: December 2006

The difference between caring for and caring about students
What's it like to be queer here?
Authors: Hill Robert J.
Published: December 2006

This chapter looks at what it is like to be queer in organizations, with an emphasis on adult and continuing education providers.
Queer challenges in organizational settings: Complexity, paradox, and contradiction
Authors: Hill Robert J.
Published: December 2006

This chapter highlights the major themes presented in this volume. It also offers a glimpse into LGBTQ issues in organizational settings that remain underrepresented in adult, continuing, and higher education.
Nanostructures by self‐assembling peptide amphiphile as potential selective drug carriers
Authors: Accardo Antonella , Tesauro Diego , Mangiapia Gaetano , Pedone Carlo , Morelli Giancarlo
Published: December 2006

The self‐assembling behavior, at physiological pH, of the amphiphile peptide (C18)2L5CCK8 in nanostructures is reported. Stable aggregates presenting a critical micellar concentration of 2 × 10−6 mol kg−1, and characterized by water exposed CCK8 peptide in β‐sheet conformation, are obtained. Small angle neutron scattering experiments are indicative for a 3D structure with dimensions ≥100 nm. AFM images confirm the presence of nanostructures. Fluorescence experiments indicating the sequestration of pyrene, chosen as drug model, and the anticancer Doxorubicin within the nanostructures are reported. © 2006 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 88: 115–121, 2007.

This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com
Solvent Polarity Controls the Helical Conformation of Short Peptides Rich in Cα‐Tetrasubstituted Amino Acids
Authors: Bellanda Massimo , Mammi Stefano , Geremia Silvano , Demitri Nicola , Randaccio Lucio , Broxterman Quirinus B. , Kaptein Bernard , Pengo Paolo , Pasquato Lucia , Scrimin Paolo
Published: December 2006

The two peptides, rich in Cα‐tetrasubstituted amino acids, Ac‐[Aib‐L‐(αMe)Val‐Aib]2‐L‐His‐NH2 (1) and Ac‐[Aib‐L‐(αMe)Val‐Aib]2‐O‐tBu (2 a) are prevalently helical. They present the unique property of changing their conformation from the α‐ to the 310‐helix as a function of the polarity of the solvent: α in more polar solvents, 310 in less polar ones. Conclusive evidence of this reversible change of conformation is reported on the basis of the circular dichroism (CD) spectra and a detailed two‐dimensional NMR analysis in two solvents (trifluoroethanol and methanol) refined with molecular dynamics calculations. The X‐ray diffractometric analysis of the crystals of both peptides reveals that they assume a prevalent 310‐helix conformation in the solid state. This conformation is practically superimposable on that obtained from the NMR analysis of 1 in methanol. The NMR results further validate the reported CD signature of the 310‐helix and the use of the CD technique for its assessment.
3D Architectures of Iron Molybdate: Phase Selective Synthesis, Growth Mechanism, and Magnetic Properties
Authors: Ding Yi , Yu Shu‐Hong , Liu Chen , Zang Zheng‐An
Published: December 2006

Monoclinic and orthorhombic Fe2(MoO4)3 microsized particles with complex 3D architectures have been selectively prepared by a template‐free hydrothermal process. The pH value, reaction time, temperature, and molybdenian source have crucial influence on the phase formation, shape evolution, and microstructures. Monoclinic Fe2(MoO4)3 particles obtained at pH 1 and pH 1.65 display ferromagnetic ordering at 10.4 K and 10.5 K, respectively, and the ferromagnetic component is determined to be 0.0458 μB and 0.0349 μB per Fe‐ion at 10 K, respectively. For orthorhombic β‐Fe2(MoO4)3, antiferromagnetic ordering was observed about 12 K. At higher temperatures, β‐Fe2(MoO4)3 began to follow the Curie–Weiss law with θ=−70 K. Such 3D architectures of monoclinic and orthorhombic β‐Fe2(MoO4)3 microparticles with unique shapes and structural characteristics may find applications as catalysts and as well as in other fields.
Drosophila photoreceptors express cysteine peptidase tan
Authors: Wagner Stefanie , Heseding Christiane , Szlachta Kamila , True John R. , Prinz Heino , Hovemann Bernhard T.
Published: December 2006

The Drosophila mutant tan (t) shows reciprocal pigmentation defects compared with the ebony (e) mutant. Visual phenotypes, however, are similar in both flies: Electroretinogram (ERG) recordings lack “on” and “off” transients, an indication of impaired synaptic transmission to postsynaptic cells L1 and L2. Cloning of tan revealed transcription of the gene in the retina, apparently in photoreceptor cells. We expressed Tan in Escherichia coli and confirmed by Western blotting and mass spectroscopic analyses that Tan is expressed as preprotein, followed by proteolytic cleavage into two subunits at a conserved —Gly—Cys— motif like its fungal ortholog isopenicillin‐N N‐acyltransferase (IAT). Tan thus belongs to the large family of cysteine peptidases. To discriminate expression of Tan and Ebony in retina and optic neuropils, we raised antisera against specific Tan peptides. Testing for colocalization with GMR‐driven n‐Syb‐GFP labeling revealed that Tan expression is confined to the photoreceptor cells R1–R8. A close proximity of Tan and Ebony expression is evident in lamina cartridges, where three epithelial glia cells envelop the six photoreceptor terminals R1–R6. In the medulla, R7/R8 axonal terminals appeared lined up side by side with glial extensions. This local proximity supports a model for Drosophila visual synaptic transmission in which Tan and Ebony interact biochemically in a putative histamine inactivation and recycling pathway in Drosophila. J. Comp. Neurol. 500:601–611, 2007. © 2006 Wiley‐Liss, Inc.
Expression of GATA3 and tenascin in the avian vestibular maculae: Normative patterns and changes during sensory regeneration
Authors: Warchol Mark E. , Speck Judith D.
Published: December 2006

Sensory receptors in the vestibular organs of birds can regenerate after ototoxic injury. Notably, this regenerative process leads to the restoration of the correct patterning of hair cell phenotype and afferent innervation within the repaired sensory epithelium. The molecular signals that specify cell phenotype and regulate neuronal guidance during sensory regeneration are not known, but they are likely to be similar to the signals that direct these processes during embryonic development. The present study examined the recovery of hair cell phenotype during regeneration in the avian utricle, a vestibular organ that detects linear acceleration and head orientation. First, we show that Type I hair cells in the avian vestibular maculae are immunoreactive for the extracellular matrix molecule tenascin and that treatment with the ototoxic antibiotic streptomycin results in a nearly complete elimination of tenascin immunoreactivity. Cells that express tenascin begin to recover after about 2 weeks and are then contacted by calyx terminals of vestibular neurons. In addition, our previous work had shown that the zinc finger transcription factor GATA3 is uniquely expressed within the striolar reversal zone of the utricle (Hawkins et al. [2003] Hum Mol Genet 12:1261–1272), and we show here that this regionalized expression of GATA3 is maintained after severe hair cell lesions and after transplantation of the sensory epithelium onto a chemically defined substrate. In contrast, the expression of three other supporting cell markers—α‐ and β‐tectorin and SCA—is reduced following ototoxic injury. These observations suggest that GATA3 expression may maintain positional information in the maculae during sensory regeneration. J. Comp. Neurol. 500:646–657, 2007. © 2006 Wiley‐Liss, Inc.
Effects of double and triple bonds on the spatial representations of odorants in the rat olfactory bulb
Authors: Johnson Brett A. , Ong Joan , Lee Kaman , Ho Sabrina L. , Arguello Spart , Leon Michael
Published: December 2006

Many naturally occurring volatile chemicals that are detected through the sense of smell contain unsaturated (double or triple) carbon‐carbon bonds. These bonds can affect odors perceived by humans, yet in a prior study of unsaturated hydrocarbons we found only very minor effects of unsaturated bonds. In the present study, we tested the possibility that unsaturated bonds affect the recognition of oxygen‐containing functional groups, because humans perceive odor differences between such molecules. We therefore compared spatial activity patterns across the entire glomerular layer of the rat olfactory bulb evoked by oxygen‐containing odorants differing systematically in the presence, position, number, and stereochemistry of unsaturated bonds. We quantified activity patterns by mapping [14C]2‐deoxyglucose uptake into anatomically standardized data matrices, which we compared statistically. We found that the presence and number of unsaturated bonds consistently affected activity patterns, with the largest effect related to the presence of a triple bond. Effects of bond saturation included a loss of activity in glomeruli strongly activated by the corresponding saturated odorants and/or the presence of activity in areas not stimulated by the corresponding saturated compounds. The position of double bonds also affected patterns of activity, but cis vs. trans configuration had no measurable impact in all five sets of stereoisomers that we studied. These results simultaneously indicate the importance of interactions between carbon‐carbon bond types and functional groups in the neural coding of odorant chemical information and highlight the emerging concept that the rat olfactory system is more sensitive to certain types of chemical differences than others. J. Comp. Neurol. 500:720–733, 2007. © 2006 Wiley‐Liss, Inc.
Entorhinal cortex of the monkey: VII. Intrinsic connections
Authors: Chrobak James J. , Amaral David G.
Published: December 2006

The organization of intrinsic connections within the entorhinal cortex was investigated in Macaca fascicularis monkeys. Anterograde tracers (3H‐amino acids, Phaseolus vulgaris‐leucoagglutinin, biotinylated dextran amine, or Fluoro‐Ruby) were injected into the deep or superficial layers of the entorhinal cortex in 24 animals. These injections labeled extensive intrinsic projections that terminated throughout all layers of the entorhinal cortex. Labeling was typically continuous i.e., there was no evidence of a patchy or columnar organization. Each injection produced a rostrocaudally oriented band of labeled fibers and terminals that extended for one‐third to one‐half of the length of the entorhinal cortex. The more extensive distributions of labeled fibers were more typical of caudally placed injection sites. Taken together, the projections identified at least two mediolaterally differentiated bands: a lateral band that encompasses fields Elr, Elc, and the most lateral aspect of fields Ec and Ecl and a wider, medially situated band that encompasses much of fields Er, Ei, Ec, and Ecl. We obtained some evidence that field Eo constitutes a third, very medially placed band. The rostrocaudal organization of labeled fibers and the extent of labeling within the deep and superficial layers were unrelated to the laminar position of the injection. These data suggest that intrinsic associatonal connections in the monkey entorhinal cortex are organized into separate associational networks. Our findings are discussed with reference to the role of interlaminar connections in mediating physiological interactions between the neocortex and the hippocampus. J. Comp. Neurol. 500:612–633, 2007. © 2006 Wiley‐Liss, Inc.
Diversity of glycine receptors in the mouse retina: Localization of the α4 subunit
Authors: Heinze Liane , Harvey Robert J. , Haverkamp Silke , Wässle Heinz
Published: December 2006

Glycine and γ‐aminobutyric acid (GABA) are the major inhibitory neurotransmitters in the retina. Approximately half of the amacrine cells release glycine at their synapses with bipolar, other amacrine, and ganglion cells. Whereas the retinal distributions of glycine receptor (GlyR) subunits α1, α2, and α3 have been mapped, the role of the α4 subunit in retinal circuitry remains unclear. A rabbit polyclonal antiserum was raised against a peptide that comprises the C‐terminal 14 amino acids of the mouse GlyR α4 subunit. Using immunocytochemistry, we localized the α4 subunit in the inner plexiform layer (IPL) in brightly fluorescent puncta, which represent postsynaptically clustered GlyRs. This was shown by double‐labeling sections for GlyR α4 and synaptic markers (bassoon, gephyrin). Double‐labeling sections for GlyR α4 and the other GlyR α subunits shows that they are mostly clustered at different synapses; however, ∼30% of the α4‐containing synapses also express the α2 subunit. We also studied the pre‐ and postsynaptic partners at GlyR α4‐containing synapses and found that displaced (ON‐) cholinergic amacrine cells prominently expressed the α4 subunit. The density of GlyR α4‐expressing synapses in wildtype, Glra1ot/ot, and Glra3−/− mouse retinas did not differ significantly. Thus, there is no apparent compensation of the loss of α1 or α3 subunits by an upregulation of α4 subunit gene expression; however, the α2 subunit is moderately upregulated. J. Comp. Neurol. 500:693–707, 2007. © 2006 Wiley‐Liss, Inc.
Hypothalamic and brainstem sources of pituitary adenylate cyclase‐activating polypeptide nerve fibers innervating the hypothalamic paraventricular nucleus in the rat
Authors: Das Mahasweta , Vihlen Christopher S. , Legradi Gabor
Published: December 2006

The hypothalamic paraventricular nucleus (PVN) coordinates major neuroendocrine and behavioral mechanisms, particularly responses to homeostatic challenges. Parvocellular and magnocellular PVN neurons are richly innervated by pituitary adenylate cyclase‐activating polypeptide (PACAP) axons. Our recent functional observations have also suggested that PACAP may be an excitatory neuropeptide at the level of the PVN. Nevertheless, the exact localization of PACAP‐producing neurons that project to the PVN is not understood. The present study examined the specific contribution of various brain areas sending PACAP innervation to the rat PVN by using iontophoretic microinjections of the retrograde neuroanatomical tracer cholera toxin B subunit (CTb). Retrograde transport was evaluated from hypothalamic and brainstem sections by using multiple labeling immunofluorescence for CTb and PACAP. PACAP‐containing cell groups were found to be retrogradely labeled from the PVN in the median preoptic nucleus; preoptic and lateral hypothalamic areas; arcuate, dorsomedial, ventromedial, and supramammillary nuclei; ventrolateral midbrain periaqueductal gray; rostral and midlevel ventrolateral medulla, including the C1 catecholamine cell group; nucleus of the solitary tract; and dorsal motor nucleus of vagus. Minor PACAP projections with scattered double‐labeled neurons originated from the parabrachial nucleus, pericoeruleus area, and caudal regions of the nucleus of the solitary tract and ventrolateral medulla. These observations indicate a multisite origin of PACAP innervation to the PVN and provide a strong chemical neuroanatomical foundation for interaction between PACAP and its potential target neurons in the PVN, such as parvocellular CRH neurons, controlling physiologic responses to stressful challenges and other neuroendocrine or preautonomic PVN neurons. J. Comp. Neurol. 500:761–776, 2007. © 2006 Wiley‐Liss, Inc.
Steady‐state 3D rolling‐contact using boundary elements
Authors: Abascal R. , Rodríguez‐Tembleque L.
Published: December 2006

This work presents a new approach to the steady‐state rolling contact problem for 3D elastic bodies. The problem solution is achieved by minimizing a general function representing the equilibrium equation and the rolling‐contact restrictions. The boundary element method is used to compute the elastic influence coefficients of the surface points involved in the contact (equilibrium equations); while the contact conditions are represented with the help of projection functions. Finally, the minimization problem is solved by the generalized Newton's method with line search. Classic rolling problems are also solved and commented. Copyright © 2006 John Wiley & Sons, Ltd.
Improving the diagnosis and prediction of customer churn: A heterogeneous hazard modeling approach
Authors: Jamal Zainab , Bucklin Randolph E.
Published: December 2006

The authors develop a hazard modeling approach to predict customer churn and to study the nature of the empirical link between customer churn and factors such as customer service experience, failure recovery, and payment equity. The approach uses a latent class Weibull hazard model with time-varying covariates. The model incorporates heterogeneity in both baseline hazard probabilities and in response parameters. The authors apply the model to the churn prediction problem at a continuous service provider, a direct-to-home satellite television firm based in a South American country. The empirical results show that the prediction of customer churn is significantly improved when heterogeneity is added to the customer churn rates and to the response parameters. Significant links are found between churn rates and variables capturing customer service experience, failure recovery efforts, and payment equity. Results also show important differences in the magnitude and significance of the response parameters across latent classes.
Dynamic e-targeting using learning spatial choice models
Authors: Jank Wolfgang , Kannan P.K.
Published: December 2006

Most CRM applications use static scoring methods to target customers; however, the fast-changing environment of the Internet often demands dynamic models that are able to adapt to changes “on the fly.” Here, we focus on location-based dynamic targeting of customers by proposing spatial models of choice that adapt to dynamically changing environments. These learning spatial choice models incorporate new information as it becomes available and are superior to their static counterparts. We estimate these models using a version of the Expectation-Maximization (EM) algorithm. We illustrate their application in the context of an online publishing firm's data on customer choice and explain how they can be useful in setting targeted e-coupon promotions or dynamic pricing application. Our studies and simulations show that learning models have superior predictive capabilities over a pure static approach and thus are ideally suited for dynamic environments.
Price customization using price thresholds estimated from scanner panel data
Authors: Terui Nobuhiko , Dahana Wirawan Dony
Published: December 2006

This study explores a customized pricing strategy based on heterogeneous price thresholds estimated from scanner panel data and shows that a customized pricing strategy could be more efficient than a flat pricing strategy. We apply a heterogeneous brand choice model with price thresholds to the price customization problem and show that heterogeneous price thresholds provide valuable information for customizing prices to individual consumers. The expected incremental profits from customized discounting as well as customized price hike are evaluated using hierarchical Bayes modeling with the Markov chain Monte Carlo method.
Retailer promotion planning: Improving forecast accuracy and interpretability
Authors: Trusov Michael , Bodapati Anand V. , Cooper Lee G.
Published: December 2006

This article considers the supermarket manager's problem of forecasting demand for a product as a function of the product's attributes and of market control variables. To forecast sales on the stock keeping unit (SKU) level, a good model should account for product attributes, historical sales levels, and store specifics, and to control for marketing mix. One of the challenges here is that many variables which describe product, store, or promotion conditions are categorical with hundreds or thousands of levels in a single attribute. Identifying the right product attributes and incorporating them correctly into a prediction model is a very difficult statistical problem. This article proposes an analytical engine that combines techniques from statistical market response modeling, datamining, and combinatorial optimization to produce a small, efficient rule set that predicts sales volume levels.
“Adaptive” learning and “proactive” customer relationship management
Authors: Sun Baohong , Li Shibo , Zhou Catherine
Published: December 2006

Customer Relationship Management (CRM) is about introducing the right product to the right customer at the right time through the right channel to satisfy the customer's evolving demands; however, most existing CRM practice and academic research focuses on methods to select the most profitable customers for a scheduled CRM intervention. In this article, we discuss a two-step procedure comprising “adaptive learning” and “proactive” CRM decisions. We also discuss three key components for customer-centric CRM: adaptive learning, forward-looking, and optimization. We then formulate CRM interventions as solutions to a stochastic dynamic programming problem under demand uncertainty in which the company learns about the evolution of customer demand as well as the dynamic effect of its marketing interventions, and make optimal CRM decisions to balance the cost of interventions and the long-term payoff. Finally, we choose two examples to demonstrate the input, output, and benefit of “adaptive” learning and “proactive” CRM.
TBid mediated activation of the mitochondrial death pathway leads to genetic ablation of the lens in Xenopus laevis
Authors: Du Pasquier D. , Chesneau A. , Ymlahi‐Ouazzani Q. , Boistel R. , Pollet N. , Ballagny C. , Sachs L.M. , Demeneix B. , Mazabraud A.
Published: December 2006

Xenopus is a well proven model for a wide variety of developmental studies, including cell lineage. Cell lineage in Xenopus has largely been addressed by injection of tracer molecules or by micro‐dissection elimination of blastomeres. Here we describe a genetic method for cell ablation based on the use of tBid, a direct activator of the mitochondrial apoptotic pathway. In mammalian cells, cross‐talk between the main apoptotic pathways (the mitochondrial and the death domain protein pathways) involve the pro‐death protein BID, the active form of which, tBID, results from protease truncation and translocation to mitochondria. In transgenic Xenopus, restricting tBID expression to the lens‐forming cells enables the specific ablation of the lens without affecting the development of other eye structures. Thus, overexpression of tBid can be used in vivo as a tool to eliminate a defined cell population by apoptosis in a developing organism and to evaluate the degree of autonomy or the inductive effects of a specific tissue during embryonic development. genesis 45:1–10, 2007. © 2006 Wiley‐Liss, Inc.
Transient expression of FOXP3 in human activated nonregulatory CD4+ T cells
Authors: Wang Jun , Ioan‐Facsinay Andreea , van der Voort Ellen I. H. , Huizinga Tom W. J. , Toes René E. M.
Published: December 2006

Foxp3 plays a key role in CD4+CD25+ Treg cell function in mice and represents a specific marker for these cells. Despite the strong association between FOXP3 expression and regulatory function in fresh human T cells, little is known about the dynamics of endogenous FOXP3 expression and its relation to the suppressive function in activated human T cells. Here, we addressed the dynamics of FOXP3 expression during human CD4+ T cell activation by plate‐bound anti‐CD3 Ab as well as the relationship between its expression and regulatory function at the single‐cell level. Our data show that FOXP3 is expressed in a high percentage of activated T cells after in vitro stimulation of human CD4+CD25– cells. FOXP3 expression is strongly associated with hyporesponsiveness of activated T cells, but is not directly correlated with their suppressive capabilities, as we demonstrate that it is also expressed in activated nonsuppressive T cells. However, in this nonsuppressive T cell population, FOXP3 expression is transient, while it is stably expressed in activated T cells that do display suppressive function, and in natural CD4+CD25++ Treg cells. These data indicate that expression of endogenous FOXP3, in humans, is not sufficient to induce regulatory T cell activity or to identify Treg cells.

See accompanying commentary http://dx.doi.org/10.1002/eji.200636929
Activation of CD4+CD25+ regulatory T cell suppressor function by analogs of the selecting peptide
Authors: Larkin Joseph , Picca Cristina Cozzo , Caton Andrew J.
Published: December 2006

CD4+CD25+Foxp3+ regulatory T (Treg) cells can undergo both thymic selection and peripheral expansion in response to self peptides that are agonists for their T cell receptors (TCR). However, the specificity by which these TCR must recognize peptide:MHC complexes to activate Treg cell function is not known. We show that CD4+CD25+Foxp3+ Treg cells can mediate suppression in response to peptides that are only weakly cross‐reactive with the self peptide that induced their formation in vivo. Moreover, suppression could be efficiently activated by peptide analogs that were inefficient at inducing CD69 up‐regulation, and that also induced little or no proliferation of naïve CD4+CD25–Foxp3– T cells expressing the same TCR. These findings provide evidence that self peptide‐specific CD4+CD25+Foxp3+ Treg cells can exert regulatory function in response to self‐ and/or pathogen‐derived peptides with which they are only weakly cross‐reactive.
TACI attenuates antibody production costimulated by BAFF‐R and CD40
Authors: Sakurai Daisuke , Kanno Yumiko , Hase Hidenori , Kojima Hidefumi , Okumura Ko , Kobata Tetsuji
Published: December 2006

B cell activating factor of the TNF family (BAFF), plays critical roles in B cell survival, activation, differentiation, and antibody (Ab) production. BAFF binds to three receptors: BAFF‐R, transmembrane activator and calcium‐modulator and cyclophilin ligand interactor (TACI) and B cell maturation antigen. While BAFF‐R is the primary receptor for B cell costimulation by BAFF, TACI is reported to serve as a positive or negative regulator for B cell responses depending on conditions. To determine the real role of TACI in B cell responses, we examined the functional relationship between TACI and BAFF‐R in Ab production from human peripheral blood B cells using agonistic mAb. BAFF‐R and CD40 enhanced IgG secretion and B cell proliferation, which were inhibited by TACI. Although TACI induced mild B cell apoptosis, its extent did not correlate with that of TACI‐mediated inhibition of IgG secretion. In addition, TACI inhibited B‐lymphocyte‐induced maturation protein‐1 expression, IgG secretion from previously IgG‐negative selected B cells, and activation‐induced cytidine deaminase expression enhanced by BAFF‐R and CD40. Importantly, BAFF‐R and CD40 enhanced B cell responsiveness to TACI‐mediated suppression. Thus, BAFF may attenuate T cell‐independent and ‐dependent B cell responses by TACI.

See accompanying commentary http://dx.doi.org/10.1002/eji.200636914
Macrophage fusion induced by IL‐4 alternative activation is a multistage process involving multiple target molecules
Authors: Helming Laura , Gordon Siamon
Published: December 2006

Multinucleated giant cells, characteristic of granulomatous infections, originate from fusion of macrophages, however, little is known about the underlying mechanism. Alternative activation of macrophages by exposure to IL‐4 and IL‐13 induces macrophage homokaryon formation. We have established a new quantitative bifluorescent system to study IL‐4‐induced fusion of primary murine macrophages in vitro. Using this assay, we could show that macrophage fusion is not mediated by a single molecule, but involves multiple functional components. Although several murine macrophage populations were not competent to form giant cells, indicating that they fail to display the full fusion machinery, these non‐fusogenic macrophages could fuse with fusion‐competent macrophages in a heterophilic manner. Since IL‐4 induced molecules were needed on both fusion partners, we conclude that at least two functionally distinct molecules mediate macrophage homokaryon formation with each present on one fusion partner. In addition, though IL‐4 treatment led to induction of a fusogenic status, macrophages could only fuse efficiently when adherent to a permissive substratum. Based on our findings, we conclude that macrophage fusion is a multistage process involving multiple target molecules. The model we describe will allow analysis of the molecular basis of membrane fusion and possible insight into alternative activation of macrophages.

See accompanying commentary: http://dx.doi.org/10.1002/eji.200636910
Enantiopure (9‐Anthryl)(2‐piperidyl)‐ and (9‐Anthryl)(2‐pyridyl)methanols – Their Use as Chiral Modifiers for Heterogeneous Hydrogenation of Keto Esters over Pt/Al2O3
Authors: Solladié‐Cavallo Arlette , Marsol Claire , Azyat Khalid , Roje Marin , Welch Christopher , Chilenski Jennifer , Taillasson Philippe , D'Orchymont Hugues
Published: December 2006

A route toward the synthesis of the erythro isomer of (9‐anthryl)(2‐piperidyl)methanol is presented as well as resolution and assignment of the structure (through NMR). The use of both the erythro and threo enantiopure isomers of this new amino alcohol, and its precursor [(9‐anthryl)(2‐pyridyl)methanol], as chiral modifiers for the Pt/Al2O3 hydrogenation of ethyl lactate showed that the erythro isomer is not necessarily the most efficient chiral modifier. This is probably because of the 9‐anthryl group. The enantioselectivities that this compound provides are not, as one would expect, higher than those observed with the naphthyl group.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
The Structural Identification and Conformational Analysis of the Products from the Reaction of Acrolein with 2′‐Deoxycytidine, 1‐Methylcytosine and Calf Thymus DNA
Authors: Pawłowicz Agnieszka J. , Klika Karel D. , Kronberg Leif
Published: December 2006

LC‐MS analysis of the reaction mixture of 2′‐deoxycytidine and acrolein in phosphate buffer under physiological conditions showed the formation of three major product peaks. The products were characterized as cyclic adducts comprised of one or two units derived from acrolein. The first (8) and third (9) eluting peaks were each found to be a pair of diastereomers of a two‐ring‐fused adduct, 6,9‐dihydroxy‐2‐(2′‐deoxy‐β‐D‐erythro‐pentofuranosyl)‐2,5,6,7,8,9‐hexahydro‐4H‐2,3a,6a‐triazaphenalen‐3‐one, whilst the second eluting peak (7) was identified as a one‐ring‐fused adduct, 2‐hydroxy‐7‐(2′‐deoxy‐β‐D‐erythro‐pentofuranosyl)‐2,3,4,7‐tetrahydropyrimido[1,6‐a]pyrimidin‐6‐one. The reaction of 1‐methylcytosine with acrolein was also examined resulting in the formation of an additional regioisomeric two‐ring‐fused adduct, 2‐hydroxy‐7‐methyl‐3,4,7,9,10,10a‐hexahydro‐2H‐1‐oxa‐4a,7,8a‐triazaphenanthren‐8‐one, not observed in the corresponding reaction with 2′‐deoxycytidine. The structures, stereochemistry and conformational analysis of the adducts and their decomposition products were resolved by spectrometric and spectroscopic studies. From the incubation of acrolein with double‐ and single‐stranded DNA and subsequent LC‐MS/MS analysis (in multiple reaction monitoring mode) of the hydrolysate, compounds were detected corresponding (i.e. identical Rt and MS) to the peaks that represented the pair of diastereomers 7 and 9.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
Chiral (–)‐DIOP Ruthenium Complexes for Asymmetric Radical Addition and Living Radical Polymerization Reactions
Authors: Iizuka Yusuke , Li Zhaoming , Satoh Kotaro , Kamigaito Masami , Okamoto Yoshio , Ito Jun‐ichi , Nishiyama Hisao
Published: December 2006

A series of ruthenium complexes with chiral phosphane ligands (Ru2Cl4[(–)‐DIOP]3 (1), Ru(Ind)Cl[(–)‐DIOP] (2), and Ru(Cp*)Cl[(–)‐DIOP] (3), DIOP = 2,3‐(isopropylidenedioxy)‐2,3‐dihydroxy‐l,4‐bis(diphenylphosphanyl)butane) were synthesized, characterized by X‐ray crystallography, and employed in asymmetric halogen transfer radical addition and metal‐catalyzed living radical polymerization reactions of olefins, such as styrene, methyl acrylate (MA), and methyl methacrylate (MMA). X‐ray crystallographic analysis revealed the binuclear structure of 1 and the mononuclear structures of 2 and 3, which suggests that the chiral environments are established around the ruthenium center. Complexes 1 and 2 induced asymmetry in chiral addition reactions with high chemical yield and relatively high optical yield (10–30 % ee) for styrene, MA, and MMA, whereas almost no significant chiral induction was observed with the use of 3. Specifically, the highest ee was obtained for 1 with the use of styrene (32 % ee) whereas the highest ee for 2 was observed with the use of MA (21 % ee) and MMA (13 % ee). All of the metal complexes induced radical polymerizations of these vinyl monomers in conjunction with a series of haloesters as an initiator. Some systems can control the molecular weights and the terminal groups by the ruthenium‐catalyzed reversible activation of the carbon–halogen bond. However, no tacticity control was achieved with all of these DIOP‐based ruthenium complexes. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)