bluuebunny/crossref_metadata_2025 huggingface dataset:
Costs of uncontrolled chemotherapy‐induced nausea and vomiting among working‐age cancer patients receiving highly or moderately emetogenic chemotherapy
Authors: Tina Shih Ya‐Chen , Xu Ying , Elting Linda S.
Published: June 2007

BACKGROUND.

Chemotherapy‐induced nausea and vomiting (CINV) is among the most feared side effects of cancer treatment. Poorly controlled CINV may lead to additional office visits or emergency room admissions, thus increasing the overall costs of cancer care. The objective of the project was to estimate the societal costs of uncontrolled CINV among working‐age cancer patients.

METHODS.

The 1997–2002 Health and Productivity Management database, a proprietary database linking medical claims to work loss information, was used. The study population consisted of employees or their spouses who were cancer patients treated with highly or moderately emetogenic chemotherapy regimens. Costs of uncontrolled CINV were estimated by comparing the direct medical costs and indirect costs between those with and without uncontrolled CINV; all costs were normalized as monthly costs and updated to 2006 US dollars. The Wilcoxon Mann‐Whitney test was used to compare the costs differences in univariate analyses, followed by multivariate analyses.

RESULTS.

In all, 2018 patients were identified; 1771 (88%) received 5‐HT3 receptor antagonists, and uncontrolled CINV was found in 563 (28%). The estimated monthly medical costs associated with uncontrolled CINV were approximately $1300 higher for cancer patients at working ages. Subgroup analysis concluded that indirect costs per patient per month were $433 higher for those in the uncontrolled CINV group.

CONCLUSIONS.

Despite a prevalent use of the 5‐HT3 receptor antagonists, uncontrolled CINV remained a common and costly problem among cancer patients treated with highly or moderately emetogenic chemotherapy. Cancer 2007. © 2007 American Cancer Society.
Androgen receptor expressing neurons that project to the paraventricular nucleus of the hypothalamus in the male rat
Authors: Williamson Martin , Viau Victor
Published: June 2007

Androgen receptors are distributed throughout the central nervous system and are contained by a variety of nuclei that are known to project to or regulate the paraventricular nucleus (PVN) of the hypothalamus, the final common pathway by which the brain regulates the hypothalamic–pituitary–adrenal (HPA) response to homeostatic threat. Here we characterized androgen receptor staining within cells identified as projecting to the PVN in male rats bearing iontophoretic or crystalline injections of the retrograde tracer FluoroGold aimed at the caudal two‐thirds of the nucleus, where corticotropin‐releasing hormone‐expressing neurons are amassed. Androgen receptor (AR) and FluoroGold (FG) double labeling was revealed throughout the limbic forebrain, including scattered numbers of cells within the anterior and posterior subdivisions of the bed nuclei of the stria terminalis; the medial zone of the hypothalamus, including large numbers of AR‐FG‐positive cells within the anteroventral periventricular and medial preoptic cell groups. Strong and consistent colabeling was also revealed throughout the hindbrain, predominantly within the periaqueductal gray and the lateral parabrachial nucleus, and within various medullary cell groups identified as catecholaminergic, predominantly C1 and A1 neurons of the ventral medulla. These connectional data predict that androgens can act on a large assortment of multimodal inputs to the PVN, including those involved with the processing of various types of sensory and limbic information, and provide an anatomical framework for understanding how gonadal status could contribute to individual differences in HPA function. J. Comp. Neurol. 503:717–740, 2007. © 2007 Wiley‐Liss, Inc.
VGLUT1 and VGLUT2 innervation in autonomic regions of intact and transected rat spinal cord
Authors: Llewellyn‐Smith Ida J. , Martin Carolyn L. , Fenwick Natalie M. , Dicarlo Stephen E. , Lujan Heidi L. , Schreihofer Ann M.
Published: June 2007

Fast excitatory neurotransmission to sympathetic and parasympathetic preganglionic neurons (SPN and PPN) is glutamatergic. To characterize this innervation in spinal autonomic regions, we localized immunoreactivity for vesicular glutamate transporters (VGLUTs) 1 and 2 in intact cords and after upper thoracic complete transections. Preganglionic neurons were retrogradely labeled by intraperitoneal Fluoro‐Gold or with cholera toxin B (CTB) from superior cervical, celiac, or major pelvic ganglia or adrenal medulla. Glutamatergic somata were localized with in situ hybridization for VGLUT mRNA. In intact cords, all autonomic areas contained abundant VGLUT2‐immunoreactive axons and synapses. CTB‐immunoreactive SPN and PPN received many close appositions from VGLUT2‐immunoreactive axons. VGLUT2‐immunoreactive synapses occurred on Fluoro‐Gold‐labeled SPN. Somata with VGLUT2 mRNA occurred throughout the spinal gray matter. VGLUT2 immunoreactivity was not noticeably affected caudal to a transection. In contrast, in intact cords, VGLUT1‐immunoreactive axons were sparse in the intermediolateral cell column (IML) and lumbosacral parasympathetic nucleus but moderately dense above the central canal. VGLUT1‐immunoreactive close appositions were rare on SPN in the IML and the central autonomic area and on PPN. Transection reduced the density of VGLUT1‐immunoreactive axons in sympathetic subnuclei but increased their density in the parasympathetic nucleus. Neuronal cell bodies with VGLUT1 mRNA occurred only in Clarke's column. These data indicate that SPN and PPN are densely innervated by VGLUT2‐immunoreactive axons, some of which arise from spinal neurons. In contrast, the VGLUT1‐immunoreactive innervation of spinal preganglionic neurons is sparse, and some may arise from supraspinal sources. Increased VGLUT1 immunoreactivity after transection may correlate with increased glutamatergic transmission to PPN. J. Comp. Neurol. 503:741–767, 2007. © 2007 Wiley‐Liss, Inc.
Choline acetyltransferase‐immunoreactive neurons in the retina of normal and dark‐reared turtle
Authors: Lee Eun‐Jin , Merwine David K. , Padilla Monica , Grzywacz Norberto M.
Published: June 2007

Visual deprivation alters retinal‐ganglion‐cell response properties through changes in spontaneous wave‐like activity (Sernagor and Grzywacz [1996] Curr Biol 6:1503–1508). This activity depends on cholinergic synaptic transmission in the turtle retina (ibid; Sernagor and Mehta [ 2001] J Anat 199:375–383). We studied the expression of choline acetyltransferase (ChAT) by immunocytochemistry and Western blot in developing retinas of control and dark‐reared turtles. At postnatal day 0 (P0), right after hatching, ChAT‐immunoreactivity was present in the ganglion cell layer (GCL), in the inner nuclear layer (INL), and in two distinct bands of the inner plexiform layer (IPL). In P14‐ and P28‐control, and P14‐ and P28‐dark‐reared retinas, ChAT‐immunoreactivity showed similar patterns to those in P0. However, in P14‐ and P28‐dark‐reared retinas the density of ChAT‐immunoreactive cells was higher in both the INL and GCL than in P14‐ and P28‐control retinas, respectively. Moreover, Western blotting showed that ChAT protein levels were significantly increased in the dark‐reared retina compared to those of the control. TUNEL studies indicated that the difference between normal and dark‐reared conditions was not due to extra apoptosis in the former. In turn, proliferating‐cell nuclear antigen immunocytochemistry showed no extra proliferating cells in the latter. Finally, nearest‐neighbor analysis revealed that the denser population of cholinergic cells in dark‐reared turtles formed a mosaic as regular as the normal ones in the GCL. Thus, light deprivation increases the expression of ChAT, increasing the apparent density of cholinergic neurons in the developing turtle retina. J. Comp. Neurol. 503:768–778, 2007. © 2007 Wiley‐Liss, Inc.
Distribution patterns of estrogen receptor α and β in the human cortex and hippocampus during development and adulthood
Authors: González Miriam , Cabrera‐Socorro Alfredo , Pérez‐García Carlos G. , Fraser James D. , López Francisco J. , Alonso Rafael , Meyer Gundela
Published: June 2007

The expression of estrogen receptors (ERs) in the developing and adult human brain has not been clearly established, although estrogens are crucial for neuronal differentiation, synapse formation, and cognitive functions. By using immunohistochemistry, we have studied the distribution of ERα and ERβ in human cerebral cortex and hippocampus from early prenatal stages to adult life. ERα was detected in the cortex at 9 gestational weeks (GW), with a high expression in proliferating zones and the cortical plate. The staining intensity decreased gradually during prenatal development but increased again from birth to adulthood. In contrast, ERβ was first detected at 15 GW in proliferating zones, and at 16/17 GW, numerous ERβ immunopositive cells were also observed in the cortical plate. ERβ expression persisted in the adult cortex, being widely distributed throughout cortical layers II–VI. In addition, from around 15 GW to adulthood, ERα and ERβ were expressed in human hippocampus mainly in pyramidal cells of Ammon's horn and in the dentate gyrus. Western blotting and immunohistochemistry in the adult cerebral cortex and hippocampus revealed lower protein expression of ERα compared with ERβ. Double immunostaining showed that during fetal life both ERs are expressed in neurons as well as in radial glia, although only ERα is expressed in the Cajal‐Retzius neurons of the marginal zone. These observations demonstrate that the expression of ERα and ERβ displays different spatial‐temporal patterns during human cortical and hippocampal development and suggest that both ERs may play distinct roles in several processes related to prenatal brain development. J. Comp. Neurol. J. Comp. Neurol. 503:790–802, 2007. © 2007 Wiley‐Liss, Inc.
Prosurvival and proapoptotic intracellular signaling in rat spiral ganglion neurons in vivo after the loss of hair cells
Authors: Alam Shaheen A. , Robinson Barbara K. , Huang Jie , Green Steven H.
Published: June 2007

Neurons depend on afferent input for survival. Rats were given daily kanamycin injections from P8 to P16 to destroy hair cells, the sole afferent input to spiral ganglion neurons (SGNs). Most SGNs die over an ∼14‐week period after deafferentation. During this period, the SGN population is heterogeneous. At any given time, some SGNs exhibit apoptotic markers—TUNEL and cytochrome c loss—whereas others appear nonapoptotic. We asked whether differences among SGNs in intracellular signaling relevant to apoptotic regulation could account for this heterogeneity. cAMP response element binding protein (CREB) phosphorylation, which reflects neurotrophic signaling, is reduced in many SGNs at P16, P23, and P32, when SGNs begin to die. In particular, nearly all apoptotic SGNs exhibit reduced phospho‐CREB, implying that apoptosis is due to insufficient neurotrophic support. However, >32% of SGNs maintain high phospho‐CREB levels, implying access to neurotrophic support. By P60, when ∼50% of the SGNs have died, phospho‐CREB levels in surviving neurons are not reduced, and SGN death is no longer correlated with reduced phospho‐CREB. Activity in the proapoptotic Jun N‐terminal kinase (JNK)‐Jun signaling pathway is elevated in SGNs during the cell death period. This too is heterogeneous: <42% of the SGNs exhibited high phospho‐Jun levels, but nearly all SGNs undergoing apoptosis exhibited elevated phospho‐Jun. Thus, heterogeneity among SGNs in prosurvival and proapoptotic signaling is correlated with apoptosis. SGN death following deafferentation has an early phase in which apoptosis is correlated with reduced phospho‐CREB and a later phase in which it is not. Proapoptotic JNK‐Jun signaling is tightly correlated with SGN apoptosis. J. Comp. Neurol. 503:832–852, 2007. © 2007 Wiley‐Liss, Inc.
High Resolution Rovibrational Spectroscopy of Chiral and Aromatic Compounds
Authors: Albert Sieghard , Quack Martin
Published: June 2007

The analysis of selected rovibrationally resolved infrared spectra of some relatively heavy and large polyatomic molecules is reviewed. A short historical summary of the development of high resolution interferometric Fourier transform infrared (FTIR) spectrometers is given and the possibilities of the currently most highly resolving FTIR spectrometer, which is commercially available in the Bruker IFS 125 series, are discussed. The computational tools necessary to analyse FTIR spectra are described briefly. As examples of rovibrational analysis the spectra of three selected molecules CHCl2F, CDBrClF, and pyridine (C5H5N) are discussed. The spectrum of CHCl2F, a fluorochlorohydrocarbon, is of interest for a better understanding of the chemistry of the Earth’s atmosphere. CDBrClF is a chiral molecule and therefore the analysis of its rovibrational spectra provides the basis for carrying out further experiments towards the detection of molecular parity violation. The analysis of the pyridine FTIR spectra illustrates the potential of the new generation of FTIR spectrometers in the study of spectra and rovibrational dynamics of aromatic systems and molecules of potential biological interest.
The Gas‐Phase Reaction between O3 and HO Radical: A Theoretical Study
Authors: Mansergas Alex , Anglada Josep M.
Published: June 2007

We report a theoretical study on the reaction of ozone with hydroxyl radical, which is important in the chemistry of the atmosphere and in particular participates in stratospheric ozone destruction. The reaction is a complex process that involves, in the first stage, a pre‐reactive hydrogen‐bonded complex (C1), which is formed previous to two transition states (TS1 and TS2) involving the addition of the hydroxyl radical to ozone, and leads to the formation of HO4 polyoxide radical before the release of the products HO2 and O2. The reaction is computed to be exothermic by 42.72 kcal mol−1, which compares quite well with the experimental estimate, and the energy barriers of TS1 and TS2 with respect to C1 are computed to be 1.80 and 2.26 kcal mol−1 at 0 K. A kinetic study based on the variational transition state theory (VTST) predicts a rate constant, at 298 K, of 7.37×10−14 cm3 molecule−1 s−1, compared to the experimentally recommended value of 7.25×10−14 cm3 molecule−1 s−1.
Adsorption–Penetration Studies of Glucose Oxidase into Phospholipid Monolayers at the 1,2‐Dichloroethane/Water Interface
Authors: Santos Hélder A. , Ferreira Elisabete S. , Pereira Elisa J. , Pereira Carlos M. , Kontturi Kyösti , Silva Fernando
Published: June 2007

The interaction between glucose oxidase (GOx) and phospholipid monolayers is studied at the 1,2‐dichloroethane/water interface by electrochemical impedance spectroscopy. Electrochemical experiments show that the presence of GOx induces changes in the capacitance curves at both negative and positive potentials, which are successfully explained by a theoretical model based on the solution of the Poisson–Boltzmann equation. These changes are ascribed to a reduced partition coefficient of GOx and an increase of the permittivity of the lipid hydrocarbon domain. Our results show that the presence of lipid molecules enhances the adsorption of GOx molecules at the liquid/liquid interface. At low lipid concentrations, the adsorption of GOx is probably the first step preceding its penetration into the lipid monolayer. The experimental results indicate that GOx penetrates better and forms more stable monolayers for lipids with longer hydrophobic tails. At high GOx concentrations, the formation of multilayers is observed. The phenomenon described here is strongly dependent on 1) the GOx and lipid concentrations, 2) the nature of the lipid, and 3) the potential drop across the interface.
Hydrogen‐Bond‐Induced Inclusion Complex in Aqueous Cellulose/LiOH/Urea Solution at Low Temperature
Authors: Cai Jie , Zhang Lina , Chang Chunyu , Cheng Gongzhen , Chen Xuming , Chu Benjamin
Published: June 2007

It was puzzling that cellulose could be dissolved rapidly in 4.6 wt % LiOH / 15 wt % urea aqueous solution precooled to −12 °C, whereas it could not be dissolved in the same solvent without prior cooling. To clarify this important phenomenon, the structure and physical properties of LiOH and urea in water as well as of cellulose in the aqueous LiOH/urea solution at different temperatures were investigated by means of laser light scattering, 13C NMR spectroscopy, differential scanning calorimetry, Fourier transform infrared spectroscopy, wide‐angle X‐ray diffraction, and transmission electron microscopy (TEM). The results reveal that a hydrogen‐bonded network structure between LiOH, urea, and water can occur, and that it becomes more stable with decreasing temperature. The LiOH hydrates cleave the chain packing of cellulose through the formation of new hydrogen bonds at low temperatures, which result in a relatively stable complex associated with LiOH, water clusters, and cellulose. A channel inclusion complex (IC) hosted by urea could encage the cellulose macromolecule in LiOH/urea solution with prior cooling and therefore provide a rationale for forming a good dispersion of cellulose. TEM observations, for the first time, showed the channel IC in dry form. The low‐temperature step played an important role in shifting hydrogen bonds between cellulose and small molecules, leading to the dissolution of macromolecules in the aqueous solution.
Enhanced Photogeneration of Triplet Excitons in an Oligothiophene–Fullerene Blend
Authors: Schueppel R. , Uhrich C. , Pfeiffer M. , Leo K. , Brier E. , Reinold E. , Baeuerle P.
Published: June 2007

Photoinduced and transient absorption spectroscopy is used to study triplet exciton dynamics in thin films of a new thiophene‐based oligomer (DCV3T) and blends of DCV3T and fullerene C60. We find enhanced DCV3T triplet exciton generation in the blend layer, which is explained as an excitonic ping–pong effect: singlet energy transfer from DCV3T to C60, followed by immediate intersystem crossing to C60, and triplet exciton back‐transfer. Estimations of the rate constants involved show that the ping–pong effect has an overall efficiency close to unity. The singlet–singlet energy transfer from DCV3T to C60 is demonstrated by efficient quenching of DCV3T luminescence in the blend, leading to sensitized emission of C60. We discuss a promising new concept of solar cells with an enlarged active‐layer thickness based on potentially long‐ranged triplet exciton diffusion in combination with efficient intersystem crossing.
Investigations on nucleation, thermodynamical parameters and growth of Benzimidazole crystals from low temperature solution
Authors: Kanagasekaran T. , Mythili P. , Srinivasan P. , Vijayan N. , Gopalakrishnan R. , Ramasamy P.
Published: June 2007

Metastable zonewidth and induction period measurements of Benzimidazole (BMZ) are presented. The nucleation parameters such as interfacial tension, radius of the critical nucleus and critical free energy change have been calculated for the solution grown Benzimidazole (BMZ) single crystals at different supersaturation ratios. The grown BMZ crystals were characterized by the differential scanning calorimetric studies for analysis of thermal properties. The dielectric behaviour of the crystal was studied at different temperature and frequency. The laser damage threshold studies show that BMZ crystal has higher laser damage threshold. (© 2007 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Crystal structure of a polar nematogen 4‐(trans‐ 4‐undecylcyclohexyl) isothiocyanatobenzene
Authors: Biswas S. , Haldar S. , Mandal P. K. , Goubitz K. , Schenk H. , Dabrowski R.
Published: June 2007

Crystal and molecular structures of a nematogenic compound 4‐(trans‐ 4‐undecylcyclohexyl) isothiocyanatobenzene (11CHBT) have been determined by direct methods using single crystal X‐ray diffraction data. The compound (C24H37N1S1) crystallizes in the monoclinic system with the space group P21/c and Z = 4. The unit cell parameters are a = 5.5539(11) Å, b = 8.1341(10) Å, c = 51.494(5) Å, and (= 91.127(14)0. The structure was refined to Rw = 0.051. The molecule is found to be slightly bow‐shaped though the alkyl chain is in all‐trans conformation. The phenyl ring and the alkyl chain are planar and the cyclohexyl group is in chair conformation. The isothiocyanato groups are almost linear. Parallel imbricated mode of packing of the molecules is found in the crystalline state which is precursor to the nematic phase structure. There are many van der Waals' interactions particularly in the isothiocyanato benzene part of the molecule. Of the various associated pairs of molecules the one having anti‐parallel configuration with overlaps in the isothiocyanato phenyl group probably exists in both the crystalline and the nematic phases. (© 2007 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Crystal structure and spectroscopic studies of a new organic monohydrogenmonophosphate dihydrate
Authors: Oueslati A. , Selmi A. , Ben Nasr C.
Published: June 2007

The crystal synthesis and structure of a new organic monohydrogenmophosphate (3,4‐Cl2‐CH2C6H3NH3)2HPO4·2H2O are reported. This compound crystallizes in the monoclinic P21/n with a = 9.081(7) Å, b = 6.501(5) Å, c = 35.423(12) Å, β = 91.09(5)°, V = 2090.9(2) Å3, and Z = 4. Crystal structure was solved and refined to R = 0.042, using 2543 independent reflections. It can be described by inorganic layers, including the HPO4‐ anions and the H2O molecules, parallel to (a, b) planes and situated at z = 0 and z = 1/2. The interlayer spacing is occupied by the organic molecules which perform different interactions around the 3D network cohesion. A characterization of this compound by solid‐state (13C, 31P) MAS NMR and IR spectroscopies is also reported. (© 2007 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Growth and high frequency dielectric study of pure and thiourea doped KDP crystals
Authors: Hussaini S. S. , Dhumane N. R. , Rabbani G. , Karmuse P. , Dongre V. G. , Shirsat M. D.
Published: June 2007

Non linear optical (NLO) materials have acquired new significance with the advent of a large number of devices utilizing solid‐state laser sources. Several NLO materials have been used for this kind of technological applications. The Potassium di‐hydrogen phosphate (KDP) one of NLO material having superior non linear optical properties has been exploited for variety of applications. In the present investigation we have grown KDP crystals from aqous solution with thiourea, an organic non linear optical material. We could enhance the SHG efficiency of thiourea doped KDP crystal. It was 1.99 times more that of pure KDP. We observed more enhancements in nonlinearity for low concentration of thiourea.The crystal structure and cell parameters of grown crystal were determined from Powder XRD.The incorporation of thiourea in the grown crystals was qualitatively analyzed from FT‐IR study. The absorption spectra of pure and thiourea doped KDP crystal reveal that thiourea doped KDP crystals would be a better nonlinear optical (NLO) material for second harmonic generation (SHG) than pure KDP. The thermal decomposition and weight loss of pure and thiourea doped KDP crystal was observed by thermogravimetric (TGA) analysis and Differential Scanning Calorimetry (DSC). The high frequency dielectric study of pure KDP crystal, thiourea doped KDP crystals and organic additive thiourea was carried out using X‐band at frequency 8GHZ and 12GHZ by transmission line wave guide method. We observed low dielectric constant of thiourea doped KDP crystal when it is doped with 2mole% of thiourea. (© 2007 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Accelerating drug development: methodology to support first‐in‐man pharmacokinetic studies by the use of drug candidate microdosing
Authors: McLean Matthew A. , Tam Chi‐Yan J. , Baratta Michael T. , Holliman Christopher L. , Ings Robert M. , Galluppi Gerald R.
Published: June 2007

Microdosing of experimental therapeutics in humans offers a number of benefits to the drug development process. Microdosing, conducted under an exploratory Investigational New Drug (IND) application, entails administration of a sub‐pharmacological dose of a new chemical entity (NCE) that allows for early evaluation of human pharmacokinetics. Such information can be pivotal for: (1) selecting a compound for full drug development from a small group of candidates; (2) defining the amount of material needed for early development; and (3) setting the initial Phase I dose regimen in humans. Appropriate safety studies must be conducted to support microdosing in humans, but the requirements are generally less extensive than those needed to support a traditional IND. To date, microdosing has not been broadly applied by the pharmaceutical industry due to concerns about analytical sensitivity and the possibility of non‐linear pharmacokinetics at extremely low doses. The primary method for detecting analytes following microdosing until now has been accelerator mass spectrometry, which is expensive, not generally available, and requires test agents to be radiolabeled. Presented in this report is an example of pharmacokinetics analysis using LC/MS/MS following microdosing of an experimental agent in cynomolgus monkeys. The results show good linearity in plasma pharmacokinetics for oral doses of 10 mg/kg (therapeutic dose) and 0.0005 mg/kg (microdose) of the test agent. The results also demonstrate the feasibility of applying standard laboratory analytics to support microdosing in humans and raise the possibility of establishing an animal model to screen for compounds having non‐linear pharmacokinetics at low dose levels. Drug Dev. Res. 68:14–22, 2007. © 2007 Wiley‐Liss, Inc.
CNS response to a thermal stressor in human volunteers and rats may predict the clinical utility of analgesics
Authors: Borsook David , Pendse Gautam , Aiello‐Lammens Mathew , Glicksman Marcie , Gostic Julie , Sherman Seth , Korn Joshua , Shaw Marnie , Stewart Ken , Gostic Richard , Bazes Shelly , Hargreaves Richard , Becerra Lino
Published: June 2007

fMRI was used to test the hypothesis that global brain activation following a stressor (a thermal stimulus) that activates multiple brain circuits in healthy subjects can predict which drugs have higher potential for clinical utility for neuropathic pain. The rationale is that a drug will modulate multiple neural circuits that are activated by the system‐specific stressor (e.g., pain). In neuropathic pain, some brain circuits have altered function, but most brain systems are “normal.” Thus, the manner in which a drug effect on neural circuits is modulated by the stressor may provide insight into the clinical utility based on the readout of brain activation in response to the stimulus. Six drugs with known clinical efficacy (or lack thereof) in treating neuropathic pain were selected and the CNS response to each drug in the presence or absence of a pain stimulus was examined. The present results suggest that it is possible to identify potentially effective drugs based on patterns of brain activation in healthy human subjects and indicate that CNS activity is a more sensitive measure of drug action than standard psychophysical measures of pain intensity. This approach was repeated in rats and showed that a similar fMRI paradigm segregates these drugs in a similar manner suggesting a potential “translational tool” in evaluating drug efficacy for neuropathic pain. The sensitivity of this paradigm using fMRI allows clinical screening in small groups of healthy subjects, suggesting it could become a useful tool for drug development as well as for elucidating the mechanisms of neuropathic disease and therapy. Drug Dev. Res. 68:23–41, 2007. © 2007 Wiley‐Liss, Inc.
Matrix metalloproteinase and aggrecanase generated aggrecan fragments: implications for the diagnostics and therapeutics of destructive joint diseases
Authors: Sumer Eren U. , Qvist Per , Tankó László B.
Published: June 2007

The degradation of extracellular matrix (ECM) components of articular cartilage is a hallmark of joint‐destructive diseases like osteoarthritis (OA) and rheumatoid arthritis (RA). A major component of the ECM is aggrecan, a proteoglycan, which is among the first matrix components to be degraded by the action of catabolic enzymes, increasingly expressed and activated during the inflammatory responses accompanying the aforementioned joint‐diseases. The two main families of enzymes are Matrix Metalloproteinases (MMPs) and aggrecanases, which both contribute to the degradation of the ECM, although their relative importance may vary between matrix components. Understanding the process of aggrecan degradation has crucial implications for improving the early diagnosis and monitoring of destructive joint‐diseases, as well as the therapeutic responses to disease‐modifying agents with potential chondroprotective effects. In the present review, we wish to provide an update on the emerging knowledge in the field obtained from ex vivo cartilage explants subjected to catabolic enzymes relevant for the pathogenesis of osteoarthritis (OA), as well as from synovial fluid of OA patients. In addition, we discuss the present status of specific immunochemical biomarker assays that were recently introduced to serve as diagnostic tools and emerging concepts of pharmacological interventions targeting the inhibition of aggrecan destruction, with the ultimate aim of decreasing the epidemiological burden of OA and rheumatoid arthritis (RA). Drug Dev Res 68:1–13, 2007. © 2007 Wiley‐Liss, Inc.
Mutual Influences of Ligands as Revealed by 2H NMR Shifts and the Angular Overlap Model Parameters: trans‐ and cis‐[CrX2(N)4]‐Type Complexes with Aliphatic Amine Ligands
Authors: Yamaguchi‐Terasaki Yukiko , Fujihara Takashi , Kaizaki Sumio
Published: June 2007

We have previously reported the relationship between 2H NMR chemical shift differences (Δδ) and the angular overlap model (AOM) parameter eσ(F), which represents the σ antibonding interaction energy obtained from the solvatochromism, for trans‐[CrF2([D4]‐3,2,3‐tet)]n+ {[D4]3,2,3‐tet = 1,10‐diamino‐4,7‐diazadecane [NH2(CH2)3NH(CD2)2NH(CH2)3NH2]} and cis‐α‐[CrF2([D4]trien)]n+ {[D4]trien = triethylenetetraamine [NH2(CH2)2NH(CD2)2NH(CH2)2NH2]}. In analogy to these relations, the co‐ligand effect on the Δδ values for cis‐α‐[CrX2([D4]trien)]n+ and trans‐[CrX2([D4]3,2,3‐tet)]n+ is found to be well correlated with the reported eσ(X) values for the co‐ligands X. This is the first example of the co‐ligand effect, or a mutual influence of ligands, associated with variation of the Cr–N and Cr–X bonds in cis‐ and trans‐[CrX2N4]‐type complexes. This Δδ vs. eσ(X) correlation offers an indirect method for estimating the eσ(X) values for didentate X2 as well as monodentate X ligands from the 2H NMR chemical shifts and ranking them in the two‐dimensional spectrochemical series. Plots of Δδ vs. eσ(FX) for trans‐[CrF(X)([D4]3,2,3‐tet)]n+ do not necessarily lie on the Δδ vs. eσ(X) correlation line for the F(X) complexes with averaged eσ(FX) = 1/2[eσ(X) + eσ(F)] values ― eσ[F(CN)] is close to eσ(F), for example ― thereby demonstrating a mutual influence between the CN– and F– ligands in the trans positions through a push‐pull action or π donor–acceptor interaction.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
New Open‐Framework Mixed‐Valence Chromium(III) Cerium(III)/(IV) Sulfate: CrCeIII7CeIV6(HSO4)6(SO4)21·75H2O
Authors: Casari Barbara M. , Langer Vratislav
Published: June 2007

The title compound, synthesized from CrVI and CeIV species, crystallizes in the space group P63 with a = 19.3015(2), c = 25.2684(4) Å, and Z = 2. The structural design of the title compound differs essentially from structures of known mixed‐valence cerium compounds which all form three‐dimensional networks. In the title compound the cerium atoms, interlinked by sulfate groups, extend to form layers held together by hydrogen‐bonding contacts. Perpendicular to these layers there are 10 Å wide channels. One third of the channels host solvent water only, while the other two thirds of the channels also host [Cr(H2O)6]3+ and [Ce(SO4)3(H2O)6]3– units, blocking each of these channels once per unit cell, resulting in 14 Å long voids.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
Controlled Stabilization and Flocculation of Gold Nanoparticles by Means of 2‐Pyrazin‐2‐ylethanethiol and Pentacyanidoferrate(II) Complexes
Authors: Toma Sergio H. , Bonacin Juliano A. , Araki Koiti , Toma Henrique E.
Published: June 2007

2‐Pyrazin‐2‐ylethanethiol (PZT) interacts with gold nanoparticles (AuNps) and pentacyanidoferrates, providing a suitable bridging ligand for the exploitation of the coordination chemistry involved in the stabilization of the colloidal solutions and in the controlled formation of aggregates in the presence of dimethyl sulfoxide. The electronic and vibrational spectra of the molecules have been investigated and discussed based on DFT and ZINDO/S theoretical calculations. The PZT‐modified AuNps exhibit strong SERS, coherent with the electromagnetic enhancement mechanism. In contrast, the charge‐transfer mechanism seems to predominate in the Raman spectra of the [Fe(CN)5PZT]3–‐modified gold nanoparticles.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
Steric and Electronic Effects in the Dimerization of Wanzlick Carbenes: The Alkyl Effect
Authors: Denk Michael K. , Hezarkhani Azardokht , Zheng Feng‐Lan
Published: June 2007

The steric and electronic influence of N‐alkyl substituents on the dimerization energies ΔG° of Wanzlick carbenes (imidazolidin‐2‐ylidenes) was investigated experimentally and through DFT methods for a series of non‐symmetrically substituted Wanzlick carbenes. A series of 3‐alkyl‐1‐tert‐butylimidazolidin‐2‐ylidenes with decreasing steric demand of the alkyl substituent (isopropyl, ethyl and methyl) were obtained in four steps from the commercially available N‐alkylaminoethanol compounds. The carbenes are hydrolytically sensitive, colorless oils that can be distilled without decomposition and show no sign of dimerization to the respective enetetramines, even after prolonged heating. Calculations at the B98/6‐31G(d) level confirm that the dimerization of all three carbenes is thermodynamically unfavorable. To separate the steric and electronic stabilization of Wanzlick carbenes by N‐alkyl substituents, the formation energies of R,H3 mono‐alkyl enetetramines were used to derive electronic increments for the N‐alkyl substituents. The computational data show that all alkyl substituents electronically stabilize Wanzlick carbenes vs. their dimerization products with increments ranging from 2.97 kcal mol–1 (N‐methyl) to as high as 6.28 kcal mol–1 (N‐tert‐butyl). For combinations of N‐methyl, N‐ethyl and N‐isopropyl substituents, the increments are additive and the dimerization energies were found to be free of noticeably steric effects. Significant steric strain was found for all tBu‐substituted carbenes with strain energies of the dimerization products ranging from 6.92 kcal mol–1 [formation of (E)‐Me2tBu2‐enetetramine] to 24.23 kcal mol–1 (formation of tBu4 enetetramine). The tert‐butyl substituent thus assumes a unique position by strongly stabilizing the carbenes electronically as well as sterically.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
Repeated Dihydrogen Elimination from Boranes and Gallanes Stabilized by Guanidine‐Type Bases: A Quantum Chemical Study Motivated by Recent Experimental Results
Authors: Ciobanu Oxana , Himmel Hans‐Jörg
Published: June 2007

Monomeric boranes and gallanes stabilized by guanidine derivatives undergo in certain cases H2 elimination reactions leading in a first step to dinuclear E(III) hydrides (E = B or Ga) and in the second step upon elimination of further H2 to dinuclear compounds with the elements in the formal oxidation state +II featuring a direct E–E bond. The thermodynamics for such H2 elimination reactions were calculated applying several methods and basis sets. In addition the calculations provide information about possible mechanisms. Thus the calculations suggest the first step to be an intramolecular H2 elimination followed by a cycloaddition reaction. The second H2 elimination, in which E–E and H–H bonds are formed at the expense of E–H bonds, is almost energy neutral, as anticipated from the small differences in electronegativity between E and H. The reaction barriers are important indicators to answer the question if H2 elimination can be made reversible. Reversible H2 elimination and addition would make this class of compounds in principle interesting for hydrogen storage applications, although obviously the weight percentage of stored dihydrogen is in the special systems presented herein not sufficient for mobile applications. The compounds can also be applied for dehydrocoupling and transfer hydrogenation to deliver a stoichiometric amount of H2 to olefins. Finally, the possibility of elimination of a third H2 leading to a dinuclear E(I) species with an E–E double bond is discussed. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
An Acyclic Aminonaphthyridine‐Based Receptor for Carbohydrate Recognition: Binding Studies in Competitive Solvents
Authors: Mazik Monika , Cavga Hüseyin
Published: June 2007

1H NMR spectroscopic and microcalorimetric titrations revealed that receptor 3b, consisting of three protonated 2‐amino‐1,8‐naphthyridine units, binds N‐acetylneuraminic acid (Neu5Ac), the most commonly occurring sialic acid, with high affinity in competitive solvents such as water/dimethyl sulfoxide. Receptor 3b is able to form neutral/charge‐reinforced hydrogen bonds and ion pairs with Neu5Ac, similar to sialic acid‐binding proteins. Furthermore, indications for weak binding of neutral sugars, such as methyl β‐D‐glucopyranoside, D‐maltose and D‐cellobiose were provided by NMR spectroscopy. Molecular modelling calculations, synthesis and binding studies in aqueous media are described. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
Performance evaluation of steel reduced flange plate moment connections
Authors: Chou Chung‐Che , Wu Chia‐Ching
Published: June 2007

This study details a new moment connection that overcomes difficulties in achieving field‐weld quality and eliminates steel beam buckling encountered in steel moment connections. This study presents cyclic test and finite element analysis results of full‐scale subassemblies using steel reduced flange plates (RFPs) to connect steel beam flanges and the column without any other direct connection. Since the RFP connection is designed as strong column‐strong beam‐weak RFPs, the RFP functions as a structural fuse that eliminates weld fractures and beam buckling. Test and analytical results show that (1) the connections transferred the entire beam flexural strength to the column and reached an interstorey drift of 4% with minor strength degradation, (2) failure of the connections was owing to buckling or fracturing of the RFP and not of the beam, and (3) the RFP connection subassembly, modelled using the nonlinear finite element computer program ABAQUS, exhibited hysteretic behaviour similar to that of the flange plate (FP) moment connection subassembly. The inelastic buckling force of the RFP was also evaluated by nonlinear regression analyses performed on a nonlinear model that relates buckling force to RFP geometries. Copyright © 2007 John Wiley & Sons, Ltd.
Discrete‐like crack simulation by smeared crack‐based FEM for reinforced concrete
Authors: Sato Yuichi , Naganuma Kazuhiro
Published: June 2007

A numerical process that simulates crack propagation in reinforced concrete through post‐crack stress redistribution is presented. This process is developed within the context of the smeared crack approach. Continuity and orientation of the reinforcing bar components are automatically recognized in the pre‐processing stage. The process explicitly outputs crack widths by computing the bond slips along reinforcement, without imposing any additional nodes between the reinforcement and concrete. The process is incorporated with a finite element algorithm, and the validation is investigated through sample 3D static analyses of nine concrete specimens subjected to monotonic shear and flexure loads. These specimens contain relatively well‐distributed steel bars and fiber reinforced polymer (FRP) sheets of reinforcement ratio from 0.11 to 0.57%. The analyses predict the crack patterns and crack widths well, although some disagreements are found between the test and the analysis results. The proposed process outputs discrete, continuous in crack directions, and element boundary‐free crack patterns. Copyright © 2007 John Wiley & Sons, Ltd.
IntServ6: an approach to support QoS over IPv6 wired and wireless networks
Authors: Padilla Jhon J. , Paradells Josep
Published: June 2007

In this paper we propose a new approach for Quality of Service (QoS) support on Internet. This approach, named IntServ6, is based on the Integrated Services Architecture (ISA). It takes advantage of the IPv6 header flow label field to improve a set of the standard ISA properties such as reservations within tunnels, flows aggregation and interconnection with MPLS transport networks. IntServ6 can be used for QoS support in IPv6 wired and wireless networks. This paper describes the IntServ6 operation and performance evaluation over both environments. Evaluation results show that this approach has a better router performance with respect to the standard IntServ. Thus, IntServ6 reduces the mean packet delay and reduces the packet delay dependence with the mobility. Copyright © 2007 John Wiley & Sons, Ltd.
Dynamic stall modelling on airfoils based on strong viscous–inviscid interaction coupling
Authors: Riziotis Vasilis A. , Voutsinas Spyros G.
Published: June 2007

The prediction of the aerodynamic performance of pitching airfoils in stall conditions is considered in the context of strong viscous–inviscid interaction modelling. The aim of the work is to demonstrate the capabilities of a low‐cost dynamic stall model well suited for engineering applications. The model is formulated on the basis of a standard panel method combined with a vortex blob approximation of the wake. The development of the boundary layer over the airfoil and the evolution of the shear layer in the wake are taken into account by means of strong viscous–inviscid interaction coupling. To this end a transpiration layer is added to the inviscid formulation which represents the displacement effect viscosity results in the flow while the non‐linear coupled equations are solved simultaneously. Separation is modelled by introducing a second wake originating from the separation point (‘double‐wake’ concept) which is provided as part of the
boundary layer solution. The theoretical presentation of the model is supported with favourable comparisons to four sets of wind tunnel measurements. Copyright © 2007 John Wiley & Sons, Ltd.
A Deep Look into the Aachen Underworld
Authors: Kukla Peter , Trautwein‐Bruns Ute
Published: June 2007

With the aid of cores and geophysical measurements, geologists have studied the complex interactions between stresses in the earth's crust and circulating bodies of water. Through these studies, it is possible to gather important insight into hidden processes occurring deep below a city
Is Medicine at German Universities as Bad as it is Painted?
Authors: Schölmerich Jürgen
Published: June 2007

Clinical research should receive more respect for the dedication shown by young researchers, more long‐term career opportunities and more transparency of funding allocation
The Amazing Diversity of Dialects in Germany
Authors: Lameli Alfred , Rabanus Stefan
Published: June 2007

The “Linguistic Atlas of the German Empire” is an exhaustive and precise documentation of the German dialects of the 19th century. The complete digitalisation of the linguistic map opens up new possibilities for international research
Sediment provenance of late Quaternary morainic, fluvial and loess‐like deposits in the southwestern Verkhoyansk Mountains (eastern Siberia) and implications for regional palaeoenvironmental reconstructions
Authors: Popp Steffen , Belolyubsky Innokenty , Lehmkuhl Frank , Prokopiev Andrei , Siegert Christine , Spektor Valentin , Stauch Georg , Diekmann Bernhard
Published: June 2007

A provenance analysis of late Quaternary deposits from tributaries of the Aldan and Lena rivers in Central Yakutia (eastern Siberia) was carried out using analysis of heavy minerals and clay mineralogy. Cluster analysis revealed one assemblage that is characterized by relatively high proportions of amphibole, orthopyroxene and garnet as well as pedogenic clay minerals, reflecting a sediment provenance from the wide catchment area of the Lena and Aldan rivers. In contrast, the three other clusters are dominated by stable heavy minerals with varying amounts of clinopyroxene, apatite and garnet, as well as high percentages of illite and chlorite that are indicative of source rocks of the Verkhoyansk Mountains. Glacial moraines reveal the local mountain source signal that is overprinted by the Lena‐Aldan signal in the oldest moraines by reworking processes. Alluvial sediments in the Verkhoyansk Foreland show a clear Lena source signal through intervals of the middle and late Pleistocene, related to a stream course closer to the mountains at that time. Loess‐like cover sediments are characterized by the dominant Lena provenance with increasing proportions of local mountain sources towards the mountain valleys. Aeolian sands in an alluvial terrace section at the mountain margin covering the time between 30 ka and 10 ka BP reflect temporarily dominant inputs of aeolian materials from the Lena Plains. Copyright © 2007 John Wiley & Sons, Ltd.
Does free complementary health insurance help the poor to access health care? Evidence from France
Authors: Grignon Michel , Perronnin Marc , Lavis John N.
Published: June 2007

The French government introduced a ‘free complementary health insurance plan’ in 2000, which covers most of the out‐of‐pocket payments faced by the poorest 10% of French residents. This plan was designed to help the non‐elderly poor to access health care. To assess the impact of the introduction of the plan on its beneficiaries, we use a longitudinal data set to compare, for the same individual, the evolution of his/her expenditures before‐and‐after enrolment in the plan. This before‐and‐after analysis allows us to remove most of the spuriousness due to individual heterogeneity. We also use information on past coverage in a difference‐in‐difference analysis to evaluate the impact of specific benefits associated with the plan. We attempt at controlling for changes other than enrolment through a difference‐in‐difference analysis within the eligible (rather than enrolled) population. Our main result is the plan's lack of an overall effect on utilization. This result is likely attributable to the fact that those who were enrolled automatically in the free plan (the majority of enrollees), already benefited from a relatively generous plan. The significant effect among those who enrolled voluntarily in the free plan was likely driven by those with no previous complementary coverage. Copyright © 2007 John Wiley & Sons, Ltd.