bluuebunny/crossref_metadata_2025 huggingface dataset:
Do futures‐based strategies enhance dynamic portfolio insurance?
Authors: Do Binh Huu , Faff Robert W.
Published: April 2004

In this paper we investigate the relative performance of two approaches to dynamic portfolio insurance: the synthetic put and the Constant Proportion Portfolio Insurance (CPPI). The investigation is conducted on the Australian market, over a sample period of 59 non‐overlapping quarters from December 1987 to December 2002. Its main contribution is to provide a comprehensive assessment of the two approaches under different market conditions, and the testing of ex ante information as an input into the trading program. The major finding is that the futures‐based implementation of both synthetic put and the CPPI approach is robust to both tranquil and turbulent market conditions in preserving the desired floor. The fact that this conclusion includes the case of employing implied volatility (obtained from the options market) is highly encouraging as it suggests high implementability of the strategy. Notably, the risk‐return tradeoff shows that portfolio insurance using this volatility measure yields a return that is 64 basis points over the risk free investment. © 2004 Wiley Periodicals, Inc. Jrl Fut Mark 24:591–608, 2004
The performance of event study approaches using daily commodity futures returns
Authors: Mckenzie Andrew M. , Thomsen Michael R. , Dixon Bruce L.
Published: April 2004

Simulations are conducted to assess the inferential accuracy of statistical event study approaches using daily futures returns. Methods examined include constant mean return models and several regression models—OLS, GARCH(1,1), and a GARCH(1,1) model having an error term with a Student'stdistribution. The simulations address four of the most commonly analyzed agricultural futures commodities—corn, soybeans, live cattle, and hogs. In terms of the size of the test statistics, constant mean return models with short normal periods perform poorly, leading to unacceptably high rejection rates of the null hypothesis. Test statistics from constant mean return models with longer normal periods, OLS, and GARCH specifications provide rejection rates largely consistent with those of a unit normal distribution. Test statistics from all models are powerful enough to detect abnormal performance levels below those that would trigger limit locks. At small levels of abnormal performance the GARCH(1,1) model with atdistribution was consistently the most powerful model. © 2004 Wiley Periodicals, Inc. Jrl Fut Mark 24:533–555, 2004
Peripapillary glial cells in the chick retina: A special glial cell type expressing astrocyte, radial glia, neuron, and oligodendrocyte markers throughout development
Authors: Quesada Adela , Prada Francisco A. , Aguilera Yolanda , Espinar Auxiliadora , Carmona Amparo , Prada Carmen
Published: April 2004

Peripapillary glial cells of the chick are a special type of glia, not only because of their position, forming a boundary between the retina on one side and the optic nerve head (ONH) and the pecten on the other, but also because although they have the same orientation and similar shape as the retinal Müller cell (a type of radial glia) and express common markers for these cells and astrocytes, they do not express glutamine synthetase (GS) or carbonic anhydrase C (CA‐C), enzymes intensely expressed by Müller cells and astrocytes. In this study, we present further molecular characterization of these cells, using immunohistochemistry techniques. We show that peripapillary glial cells express a novel neuron antigen, 3BA8, that in the adult retina is located only in one neuron type (the amacrine cell) and in the inner plexiform layer (IPL). They also express an antigen specific to myelin and oligodendrocytes, MOSP, and a glial antigen, 3CB2, expressed by radial glia and astrocytes throughout the CNS. The study of the developmental expression of these three antigens in the peripapillary glial cell territory shows different spatiotemporal labeling patterns: 3CB2 and 3BA8 are expressed much earlier (embryonic days E3 and E5, respectively) than MOSP (E12), and during a developmental window (E6–E10) 3BA8 labels the peripapillary glial cells intensely and does not label the ONH or the optic nerve (ON), which are labeled later. The expression of 3CB2 is much more intense in the peripapillary glial cells than in Müller cells from early stages of development up to E16, and the expression of MOSP starts earlier in the peripapillary glial cells than in the Müller cells and is maintained with much higher intensity in the peripapillary glial cells throughout development. These findings show that Müller and peripapillary glial cells follow independent courses of differentiation, which together with the fact that the peripapillary glial cells express molecules typical of neurons, oligodendrocytes, radial glia, and astrocytes are evidence that peripapillary glial cells are a unique type of glia in the CNS. © 2004 Wiley‐Liss, Inc.
Neuronal expression of CD22: Novel mechanism for inhibiting microglial proinflammatory cytokine production
Authors: Mott Ryan T. , Ait‐Ghezala Ghania , Town Terrence , Mori Takashi , Vendrame Martina , Zeng Jin , Ehrhart Jared , Mullan Michae , Tan Jun
Published: April 2004

Although considered an immunologically privileged site, the central nervous system (CNS) can display significant inflammatory responses, which may play a pathogenic role in a number of neurological diseases. Microglia appear to be particularly important for initiating and sustaining CNS inflammation. These cells exist in a quiescent form in the normal CNS, but acquire macrophage‐like properties (including active phagocytosis, upregulation of proteins necessary for antigen presentation, and production of proinflammatory cytokines) after stimulation with inflammatory substances such as lipopolysaccharide (LPS). Recent studies have focused on elucidating the role of neurons in the regulation of microglial inflammatory responses. In the present study, we demonstrate, using neuron‐microglial cocultures, that neurons are capable of inhibiting LPS‐induced tumor necrosis factor‐α (TNF‐α) production by microglia. This inhibition appears to be dependent on secretion of substances at axon terminals, as treatment with the presynaptic calcium channel blocker ω‐conotoxin abolishes this inhibitory effect. Moreover, we show that conditioned medium from neuronal cultures similarly inhibits microglial TNF‐α production, which provides additional evidence that neurons secrete inhibitory substances. We previously demonstrated that the transmembrane protein‐tyrosine phosphatase CD45 plays an important role in negatively regulating microglial activation. The recent characterization of CD22 as an endogenous ligand of this receptor led us to investigate whether neurons express this protein. Indeed, we were able to demonstrate CD22 mRNA and protein expression in cultured neurons and mouse brain, using reverse transcriptase‐polymerase chain reaction and antibody‐based techniques. Furthermore, we show that neurons secrete CD22, which functions as an inhibitor of microglial proinflammatory cytokine production. © 2004 Wiley‐Liss, Inc.
Evidence of active microglia in substantia nigra pars compacta of parkinsonian monkeys 1 year after MPTP exposure
Authors: Barcia Carlos , Bahillo Angel Sánchez , Fernández‐Villalba Emiliano , Bautista Víctor , Poza Y Poza Máximo , Fernández‐Barreiro Andrés , Hirsch Etienne C. , Herrero María‐Trinidad
Published: April 2004

Inflammatory changes have been found in Parkinson's disease, in humans intoxicated with the parkinsonian toxin MPTP, and in animal models of the disease. However, it is still not known whether inflammatory changes are responsible for active nerve cell death or if they have a protective role against neurodegeneration. In this study, we analyzed the glial reaction in the substantia nigra pars compacta (SNpc) and the striatum of monkeys rendered parkinsosian by chronic MPTP injections. At postmortem examination 1 year after the last MPTP injection, the density of astroglial cells and activated microglial cells in the SNpc, but not in the striatum, of MPTP‐intoxicated animals was significantly higher than in the two control animals. These data suggest that neurodegeneration was still active despite the absence of the agent triggering cell death and that the glial reaction is associated with long‐term neurodegeneration. © 2004 Wiley‐Liss, Inc.
Numeracy and the shortcomings of utility assessment in head and neck cancer patients
Authors: Schwartz Seth R. , McDowell Jennifer , Yueh Bevan
Published: April 2004

Background.

Because survival differences between surgical and nonsurgical treatment for head and neck cancer (HNC) are hard to detect, increasing focus has been placed on quality of life (QOL) differences after treatment. Utility assessment provides insight into QOL. Evidence suggests that a patient's comfort with numerical concepts (“numeracy”) may influence utility measures. We hypothesize that patients who are nonnumerate provide inconsistent utility data in QOL studies.

Methods.

New HNC (n = 18) patients were recruited to participate. Patients completed a numeracy questionnaire, a utility assessment, and a global QOL questionnaire. Higher scores reflect better function. Interviewers rated the functional level of each patient. For both numerate and nonnumerate patients, utility scores were compared with global QOL (good vs poor) and observer‐rated function.

Results.

Half of the patients were numerate. Numerate patients who rated their QOL as good had significantly higher utility scores than did patients with poor global QOL (0.95 vs 0.43, p = .03). In contrast, nonnumerate patients with good QOL had lower utility scores than did patients with poor QOL (0.45 vs 0.77, NS). Utility scores for numerate patients correlated well with observer‐rated function (r = 0.41 to r = 0.57), whereas those of nonnumerate patients did not (r = −0.16 to r = 0.06).

Conclusions.

QOL evaluation through utility assessment may provide inaccurate and contradictory data about patient functioning for nonnumerate patients. This may confound QOL assessment when interpreting utility data. © 2004 Wiley Periodicals, Inc. Head Neck 26: 401–407, 2004
CO2 laser treatment of supraglottic cancer
Authors: Motta Gaetano , Esposito Erik , Testa Domenico , Iovine Renata , Motta Sergio
Published: April 2004

Background.

The aim of the study was to evaluate the effectiveness of endoscopic CO2 laser microsurgery in the management of supraglottic cancer.

Methods.

One hundred twenty‐four patients (116 men and eight women; mean age, 59 years; range 31–81 years) with supraglottic cancer underwent CO2 laser surgery (mean follow‐up 5 years). The study patients were classified as follows: 45 patients, T1N0M0; 61 patients, T2N0M0; and 18 patients, T3N0M0. According to the staging, the following procedures were adopted: epiglottectomy, resection of aryepiglottic fold or false vocal cord in T1 patients (group A); resection of the false vocal cord and adjacent structures in T2 patients (group B); and supraglottic laryngectomy in T3 patients (group C). Statistical comparison of survival parameters was carried out with Wilcoxon test, considering p < .05 the minimum significance value.

Results.

Overall actuarial survival, adjusted actuarial survival, and no evidence of disease at 5 years were 91%, 97%, and 82% in group A; 88%, 94%, and 59% in group B; and 81%, 81%, and 51% in group C, respectively. The statistical analysis of survival parameters showed a significant difference in the comparison of T1 versus T2 and T2 versus T3 tumors (p < .01). Actuarial local control, actuarial nodal control, and actuarial distant metastasis control at 5 years were 82%, 82%, and 100% in T1 patients; 63%, 90%, and 98% in T2 patients; and 77%, 75%, and 93% in T3 patients. Laryngeal preservation rate was 88.6% in T1 patients, 85.4% in T2 patients, and 93.7% in T3 patients. Patients in groups A and B were discharged after 3 to 12 days, and patients in group C, were discharged after 14 to 20 days.

Conclusions.

The results of this study show that endoscopic CO2 laser surgery is highly effective in the treatment of T1 and T2 supraglottic cancer. In T3 cancer, the CO2 laser should be implemented in those cases where radical excision by endoscopic route is feasible. © 2004 Wiley Periodicals, Inc. Head Neck 26: 442–446, 2004
A novel population of calretinin‐positive neurons comprises reelin‐positive Cajal‐Retzius cells in the hippocampal formation of the adult domestic pig
Authors: Ábrahám Hajnalka , Tóth Zsolt , Seress László
Published: April 2004

Calretinin‐containing neurons in the hippocampal formation, including the subiculum, presubiculum, parasubiculum, and entorhinal cortex, were visualized with immunocytochemistry. Calretinin immunoreactivity was present exclusively in non‐principal cells. The largest immunoreactive cell population was found in the outer half of the molecular layer of the dentate gyrus and in the stratum lacunosum‐moleculare of Ammon's horn. A proportion of these cells were also immunoreactive for reelin, a Cajal‐Retzius cell marker. Similar calretinin‐positive cells were found in the molecular layer of the subicular complex and entorhinal cortex. In the parasubiculum, a few immunoreactive bipolar and multipolar cells could be observed in the superficial and deep pyramidal cell layers. In the entorhinal cortex, bipolar and multipolar calretinin‐positive cells were frequent in layer II, and large numbers of multipolar cells in layer V were immunoreactive. Electron microscopic analysis showed that somata of calretinin‐positive cells contained either round nuclei with smooth nuclear envelopes or nuclei with multiple deep infoldings. Immunoreactive dendrites were smooth varicose, and the apposing axon terminals formed both symmetric and asymmetric synapses. Zonula adherentia were observed between calretinin‐positive dendrites. Calretinin‐ positive axon terminals formed two types of synapses. Axon terminals with asymmetric synapses were found close to the hippocampal fissure, whereas axon terminals forming symmetric synapses innervated spiny dendrites in both the molecular layer of the dentate gyrus and in stratum lacunosum‐moleculare of Ammon's horn. Calretinin‐ positive axon terminals formed both symmetric and asymmetric synapses with calretinin‐positive dendrites. In conclusion, calretinin‐ positive neurons form two major subpopulations in the adult domestic pig hippocampus: (1) a γ‐aminobutyric acid (GABA)ergic subpopulation of local circuit neurons that innervates distal dendrites of principal cells in both the dentate gyrus and in Ammon's horn; and (2) Cajal‐Retzius type cells close to the hippocampal fissure, as well as in the molecular layer of the subicular complex and entorhinal cortex. © 2004 Wiley‐Liss, Inc.
Reduced basal CAMKII levels in hippocampal CA1 region: Possible cause of stress‐induced impairment of LTP in chronically stressed rats
Authors: Gerges N.Z. , Aleisa A.M. , Schwarz L.A. , Alkadhi K.A.
Published: April 2004

Chronic psychosocial stress markedly reduces the expression of high‐frequency stimulation (HFS)‐evoked early long‐term potentiation (LTP) in the CA1 region of the hippocampus of anesthetized rats. Immunoblotting was performed to determine changes in molecular levels of key signaling proteins that might be responsible for this inhibitory effect. Western blot analysis of the CA1 region demonstrates that chronic psychosocial stress decreases basal levels of calcium calmodulin kinase II (CaMKII), phosphorylated (P)‐CaMKII, calmodulin, and protein kinase C (PKCγ) while markedly increasing protein phosphatase 2B (calcineurin) levels. The decrease of basal levels of P‐CaMKII may be triggered primarily by excessive dephosphorylation resulting from enhanced basal levels of calcineurin. The decline in the basal levels of the upstream molecules, PKCγ and calmodulin may be a consequence of the diminished basal P‐CaMKII levels. Analysis of signaling molecules in CA1 region of chronically stressed rat subjected to HFS in vivo showed only one difference compared to similarly stimulated control rats; no increase in P‐CaMKII levels. Our results suggest that decreased P‐CaMKII levels may be primarily responsible for the stress‐induced reduction in LTP expression. © 2004 Wiley‐Liss, Inc.
Ionic mechanisms in the generation of subthreshold oscillations and action potential clustering in entorhinal layer II stellate neurons
Authors: Fransén Erik , Alonso Angel A. , Dickson Clayton T. , Magistretti Jacopo , Hasselmo Michael E.
Published: April 2004

A multicompartmental biophysical model of entorhinal cortex layer II stellate cells was developed to analyze the ionic basis of physiological properties, such as subthreshold membrane potential oscillations, action potential clustering, and the medium afterhyperpolarization. In particular, the simulation illustrates the interaction of the persistent sodium current (INaP) and the hyperpolarization activated inward current (Ih) in the generation of subthreshold membrane potential oscillations. The potential role of Ih in contributing to the medium hyperpolarization (mAHP) and rebound spiking was studied. The role of Ih and the slow calcium‐activated potassium current IK(AHP) in action potential clustering was also studied. Representations of Ih and INaP were developed with parameters based on voltage‐clamp data from whole‐cell patch and single channel recordings of stellate cells (Dickson et al., J Neurophysiol 83:2562–2579, 2000; Magistretti and Alonso, J Gen Physiol 114:491–509, 1999; Magistretti et al., J Physiol 521:629–636, 1999a; J Neurosci 19:7334–7341, 1999b). These currents interacted to generate robust subthreshold membrane potentials with amplitude and frequency corresponding to data observed in the whole cell patch recordings. The model was also able to account for effects of pharmacological manipulations, including blockade of Ih with ZD7288, partial blockade with cesium, and the influence of barium on oscillations. In a model with a wider range of currents, the transition from oscillations to single spiking, to spike clustering, and finally tonic firing could be replicated. In agreement with experiment, blockade of calcium channels in the model strongly reduced clustering. In the voltage interval during which no data are available, the model predicts that the slow component of Ih does not follow the fast component down to very short time constants. The model also predicts that the fast component of Ih is responsible for the involvement in the generation of subthreshold oscillations, and the slow component dominates in the generation of spike clusters. © 2004 Wiley‐Liss, Inc.
Mode shifting between storage and recall based on novelty detection in oscillating hippocampal circuits
Authors: Meeter M. , Murre J.M.J. , Talamini L.M.
Published: April 2004

It has been suggested that hippocampal mode shifting between a storage and a retrieval state might be under the control of acetylcholine (ACh) levels, as set by an autoregulatory hippocampo‐septo‐hippocampal loop. The present study investigates how such a mechanism might operate in a large‐scale connectionist model of this circuitry that takes into account the major hippocampal subdivisions, oscillatory population dynamics and the time scale on which ACh exerts its effects in the hippocampus. The model assumes that hippocampal mode shifting is regulated by a novelty signal generated in the hippocampus. The simulations suggest that this signal originates in the dentate. Novel patterns presented to this structure lead to brief periods of depressed firing in the hippocampal circuitry. During these periods, an inhibitory influence of the hippocampus on the septum is lifted, leading to increased firing of cholinergic neurons. The resulting increase in ACh release in the hippocampus produces network dynamics that favor learning over retrieval. Resumption of activity in the hippocampus leads to the reinstatement of inhibition. Despite theta‐locked rhythmic firing of ACh neurons in the septum, ACh modulation in the model fluctuates smoothly on a time scale of seconds. It is shown that this is compatible with the time scale on which memory processes take place. A number of strong predictions regarding memory function are derived from the model. © 2004 Wiley‐Liss, Inc.
Effect of controlled zinc release on bone mineral density from injectable Zn‐containing β‐tricalcium phosphate suspension in zinc‐deficient diseased rats
Authors: Otsuka Makoto , Ohshita Yuko , Marunaka Sunao , Matsuda Yoshihia , Ito Atsuo , Ichinose Noboru , Otsuka Kuniko , Higuchi William I.
Published: April 2004

The purpose of this study was to evaluate the efficacy of zinc (Zn)‐containing β‐tricalcium phosphate (Zn–TCP) in correcting the bone mineral deficiency noted in osteoporosis using ovariectomized rat model. Four rats were used for each of the four experimental groups: D0, D10, D20, and N10. The rats in D0, D10, and D20 groups were ovariectomized, and fed a vitamin D‐, Ca‐, and Zn‐deficient diet, and induced Zn‐deficient osteoporoses for 9 weeks. In contrast, the N10 group was the normal rats fed normal healthy diet for 9 weeks. D0 group was injected with pure β‐TCP suspension, D10 and D20 groups were injected with suspensions containing 10 mg of 10 mol % (6.17 wt % Zn) and 20 mol % (12.05 wt % Zn) Zn–TCP, respectively, and the healthy group, N10 were injected with 10 mol %. Zn–TCP suspensions. Injections were administered intramuscularly in the left thigh once a week in all rats, and fed a vitamin D‐ and Zn‐deficient diet for 9 weeks. The plasma calcium (Ca) and Zn levels, plasma alkaline phosphatase activity (ALP) and bone mineral density (BMD) of the lumbar vertebra and femora were measured. The plasma Zn levels in all the rats were between 1.1 and 2.8 μg/mL. The areas under the curves for the Ca, Zn, and ALP (Ca‐AUC, Zn‐AUC, and ALP‐AUC) levels between 0 and 63 days were calculated. Results for the AUCs were as follows: (1) the Zn‐AUCs were in the order of N10 = D20 > D10 > D0; (2) the Ca‐AUCs for D0, D10 groups were significantly lower than that for the N10 group; (3) the ALP‐AUCs for the D10 and D20 groups were significantly higher than that for the N10 group, and that of the D0 group was in between those. The body weight of D10 and D20 groups significantly increased with time, that of the D0 group increased slightly, and that of the N10 group remained unchanged for the entire experimental period. The BMD of the lumbar vertebrae of the D10 and D20 groups (about 100 mg/cm2) was significantly higher than that of the D0 group but lower than that of the N10 group. The BMD of the left femur increased more than that of the right femur with the increase in the amount of Zn in the suspension. The results of this study suggest that the local effect on BMD was more pronounced than the effect on the whole body. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res 69A: 552–560, 2004
Titanium implants enhance pulmonary nitric oxide production and lung injury in rats exposed to endotoxin
Authors: Yang Rong Sen , Tsai Keh Sung , Liu Shing Hwa
Published: April 2004

An increase in levels of elemental Ti in the blood and lung of rats with a Ti alloy implant has been demonstrated. However, the pathophysiological role of the elevated elemental Ti level in the circulation remains unclear. Rats were implanted with Ti alloy discs for 4 weeks. The levels of elemental Ti in the blood and lung were especially increased compared with other tissues. The Ti alloy implant enhanced lung injury related to endotoxin from Gram‐negative bacteria (lipopolysaccharide, LPS), which was characterized by lung edema and other histological changes such as recruitment of neutrophils, interstitial edema, and alveolar hemorrhage in the lung. In the presence of endotoxin, an increase of nitrite production was shown in the plasma and bronchoalveolar lavage fluid of rats implanted with a Ti alloy. Moreover, the Ti alloy implant further enhanced the induction of inducible nitric oxide (NO) synthase (iNOS) protein expression induced by LPS in the lung. These endotoxin‐related responses in the presence or absence of the Ti alloy implant could be inhibited by aminoguanidine (an iNOS inhibitor). These results provide the first experimental evidence that circulating Ti released from Ti alloy implants has an ability to affect pulmonary iNOS protein expression, and enhance the pathogenesis of acute lung injury during endotoxemia. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res 69A: 561–566, 2004
A comparative staining technique to detect mineral oil contaminants from orthopedic implants
Authors: Willie Bettina M. , Watts C. William , Szakacs Juliana G. , Bloebaum Roy D.
Published: April 2004

An adverse tissue response was reported in patients implanted with porous coated implants containing a mineral oil contaminant. A comparative staining technique was developed in a rabbit and sheep model to identify the presence of a mineral oil contaminant on porous coated implants by examining the surrounding tissues and end organs. The hypothesis for the study was that mineral oil, a saturated lipid, could be distinguished from unsaturated lipids such as animal fats. Frozen rabbit and sheep tissues were stained with hematoxylin and eosin, oil‐red‐O, and bromide‐silver nitrate. Twenty‐eight positive control rabbits were injected with mineral oil and 12 negative control rabbits were injected with saline into the paravertebral muscle and synovial cavity of the knee joint. Comparative analysis of tissue was conducted after 1, 3, 5, and 12 weeks. Thermally cleaned porous coated implants were implanted for 6, 12, and 24 weeks into cancellous bone of the distal femur of sheep to allow for a weight‐bearing model. The comparative histological analysis of the positive control rabbit tissue allowed for detection of mineral oil in all tissues examined. Histological analysis of sheep tissue and saline‐injected rabbit tissue showed no evidence of mineral oil or adverse tissue response. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 70B: 130–138, 2004
Hard‐tissue‐engineered zirconia porous scaffolds with hydroxyapatite sol–gel and slurry coatings
Authors: Kim Hae‐Won , Kim Hyoun‐Ee , Knowles Jonathan C.
Published: April 2004

A zirconia (ZrO2) porous scaffold was coated with a gradient apatite layer to induce osteoconductivity with the use of a combination of sol–gel and powder slurry methods. The ZrO2 was used to impart mechanical strength and the apatite layer was coated for functional biocompatibility. The coating layer, from the outside in, was composed of sol–gel hydroxyapatite (HA)/slurry HA/slurry FA. The sol–gel coating powder had a lower crystallinity than the slurry coating powder. The sol–gel HA coating over the HA/FA slurry coating layer made the surface very smooth. The sol–gel coating over the slurry coating layer enhanced the bonding strength up to 33 MPa. The dissolution rate of the sol–gel/slurry coating layer was much higher than that of the slurry coating. Moreover, the rate could be controlled by altering the heat‐treatment temperature of the sol–gel HA layer. The MG63 cells cultured on these materials grew and spread in a different manner, depending on the coating layer. However, the proliferation rates of the cells on both coating systems were not much different. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 70B: 270–277, 2004
Sphingosine 1‐phosphate and its G protein‐coupled receptors constitute a multifunctional immunoregulatory system
Authors: Goetzl Edward J. , Wang Wengang , McGiffert Christine , Huang Mei‐Chuan , Gräler Markus H.
Published: April 2004

The lysophospholipid growth factors sphingosine 1‐phosphate (S1P) and lysophosphatidic acid (LPA) are generated by many cells involved in immunity, including macrophages, dendritic cells, mast cells, and platelets, with resultant lymph and plasma concentrations of 0.1–1 μM. All immune cells express distinctive profiles of G protein‐coupled receptors (GPCRs) for S1P and LPA, which are regulated developmentally and by cellular activation. For T‐cells, constitutive S1P signaling through their principal S1P1 GPCR inhibits chemotactic responses to chemokines, with lesser suppression of proliferation and cytokine production. These S1P‐S1P1 GPCR signals tonically reduce T‐cell chemotactic sensitivity to chemokines and thereby limit homing of blood and spleen T‐cells to secondary lymphoid tissues. S1P1 GPCR antagonists evoke lymphopenia by permitting blood T‐cells to enter lymph nodes and blocking S1P1 GPCR‐dependent T‐cell efflux from lymph nodes. Inversely, there is a longer than normal persistance in blood and a decrease in lymphoid transit time for T‐cells overexpressing transgenic S1P1 GPCRs. The immunotherapeutic potential of S1P1 GPCR antagonists derives from their capacity to limit T‐cell access to organ grafts and autoimmune antigens without reducing their other intrinsic functional capabilities. Lysophospholipids and their GPCRs thus constitute an immunoregulatory system of sufficient prominence for pharmacological targeting in transplantation, autoimmunity and immunodeficiency. © 2004 Wiley‐Liss, Inc.
Effect of patient sex, clinician sex, and sex role on the diagnosis of Antisocial Personality Disorder: Models of underpathologizing and overpathologizing biases
Authors: Crosby Jeremy Paul , Sprock June
Published: April 2004

This study examined the influence of patient sex and clinician sex and sex role for a case, meeting minimum diagnostic criteria for Antisocial Personality Disorder, in which patient sex was varied. The purpose was to provide an in‐depth evaluation of the process by which patient sex and characteristics of clinicians may contribute to bias in personality disorder diagnoses. Psychologists (N = 167) read two cases, including the target case, and provided symptom ratings and diagnoses. A sex‐unspecified condition served as a baseline to assess for over‐ and underpathologizing bias, and diagnoses based on the symptom ratings were compared to assigned diagnoses. Clinician sex role was assessed using the Bem Sex Role Inventory‐Short Form. Results revealed that bias occurred when the patient's sex (female) was inconsistent with the gender weighting of the symptoms in the case (masculine), but the direction of the bias was consistent with sex roles (underdiagnosis of sex‐role‐inconsistent diagnoses, overdiagnosis of sex‐role‐consistent diagnoses). Path models of over‐ and underdiagnostic bias were developed using structural equation modeling. Patient sex had a direct effect on diagnostic ratings whereas clinician sex role had an indirect effect through symptom ratings. © 2004 Wiley Periodicals, Inc. J Clin Psychol.
A new instrument to assess participant motivation for involvement in preventive interventions
Authors: Allart‐van Dam Esther , Hosman Clemens M.H. , Keijsers Ger P.J.
Published: April 2004

The Nijmegen Motivation List for Prevention (NML‐P) is a new instrument to assess the motivation of participants for involvement in preventive group interventions. The aim of the current study was to explore the underlying dimensions of the NML‐P and the predictive potential of the instrument for those participating in a psychoeducational preventive group intervention for depression: the Coping with Depression course. Principal component analyses revealed four components: readiness to participate, social support, doubt, and burden. Preliminary prediction analyses showed doubt, support, and burden to be related to the outcome of the depression prevention intervention. © 2004 Wiley Periodicals, Inc. J Clin Psychol.
Relationships among attention deficit hyperactivity disorder, induced labor, and selected physiological and demographic variables
Authors: Claycomb Cynthia D. , Ryan Joseph J. , Miller Lori J. , Schnakenberg‐Ott Summer D.
Published: April 2004

We investigated whether events associated with physiological maternal and fetal stress during the birth process were associated with diagnosis of attention deficit hyperactivity disorder (ADHD), alone or in combination with demographic variables. We gathered data through maternal responses to a 17‐item questionnaire. Sex, mother's educational level, mother's age at delivery, interval between the beginning of labor and birth, and presence or absence of complications during the delivery process accounted for 42% of the variance in the diagnostic (ADHD) category. The model correctly classified 87% of the non‐ADHD group (n = 90) and 48% of the children with ADHD (n = 40), for an overall correct classification rate of 75%. A differential effect for sex was indicated, but a low number of females in the diagnostic category limited meaningful analysis. Maternal age at delivery and maternal education level emerged as the strongest predictors, with the exception of sex, of ADHD in the full model. © 2004 Wiley Periodicals, Inc. J Clin Psychol.
The identity of the sulfur‐containing phases present in cement clinker manufactured using a high sulfur petroleum coke fuel
Authors: Twomey C , Birkinshaw C , Breen S
Published: April 2004

Cement clinker produced using a high sulfur petroleum coke fuel has been analysed to determine the identity of the sulfate‐containing phases. Quantitative X‐ray diffraction methods were used in conjunction with extraction procedures to concentrate or extract the sulfate phases. The minerals of interest were anhydrite (CaSO4), aphthitalite (3K2SO4·Na2SO4), arcanite (K2SO4), calcium langbeinite (K2SO4·2CaSO4) and thenardite (Na2SO4). Overall sulfur content of the clinker increased in proportion with the amount of sulfur in the fuel. The clinker produced using the high sulfur fuel was found to contain a significantly increased concentration of aphthitalite but a reduced amount of thenardite. Comparison of the experimental results with theoretical predictions based on the Bogue formulae shows differences in respect of calcium langbeinite, which is not detected in the clinker, and thenardite, which is detected. Copyright © 2004 Society of Chemical Industry
Solvent extraction and purification of sugars from hemicellulose hydrolysates using boronic acid carriers
Authors: John Griffin Gregory , Shu Li
Published: April 2004

Research was performed to determine whether it was technically feasible to use boronic acid extractants to purify and concentrate the sugars present in hemicellulose hydrolysates. Initially, five types of boronic acids (phenylboronic acid, 3,5‐dimethylphenylboronic acid, 4‐tert‐butylphenylboronic acid, trans‐β‐styreneboronic acid or naphthalene‐2‐boronic acid) dissolved in an organic diluent (Shellsol® 2046 or Exxal® 10) containing the quaternary amine Aliquat® 336 were tested for their ability to extract sugars (fructose, glucose, sucrose and xylose) from a buffered, immiscible aqueous solution. Naphthalene‐2‐boronic acid was found to give the greatest extraction of xylose regardless of which diluent was used. Trials were then conducted to extract xylose and glucose from solutions derived from the dilute acid hydrolysis of sugar cane bagasse and to then strip the loaded organic solutions using an aqueous solution containing hydrochloric acid. This produced a strip solution in which the xylose concentration had been increased over 7× that of the original hydrolysate while reducing the concentration of the undesirable acid‐soluble lignin by over 90%. Hence, this process can be exploited to produce high concentration xylose solutions suitable for direct fermentation. Copyright © 2004 Society of Chemical Industry
Evaluation of a simple batch distillation process for treating wastes from metalworking industries
Authors: Cañizares P , García‐Gómez J , Martínez F , Rodrigo MA
Published: April 2004

A simple batch distillation process for the treatment of two types of industrial waste generated in a metalworking factory has been evaluated. Both types of waste are oil‐in‐water emulsions composed of numerous compounds and each type has a high content of water‐soluble species. The water‐soluble nature of the wastes precludes the use of conventional treatment technologies, such as ultrafiltration or chemical emulsion breaking, since they need to be complemented with additional treatment processes that would probably increase the cost considerably. A simple characterization of the liquid–vapour equilibrium and a scale‐up study has demonstrated the applicability of this technology. The process allows 90% of the waste to be recovered as water, thus achieving the required quality limits for discharge into a municipal wastewater treatment plant. An approximate estimation of capital investment and operating costs for an existing case has shown the economic viability of this process. Copyright © 2004 Society of Chemical Industry
Separation of cobalt and nickel from acidic sulfate solutions using mixtures of di(2‐ethylhexyl)phosphoric acid (DP‐8R) and hydroxyoxime (ACORGA M5640)
Authors: Cerpa Arisbel , Alguacil Francisco José
Published: April 2004

DP‐8R and ACORGA M5640 extractants diluted in Exxsol D100 were used to co‐extract cobalt and nickel from aqueous acidic sulfate media. The influences of equilibration time, temperature, equilibrium pH and reagent concentrations on the extraction of both metals have been studied. It was observed that both cobalt and nickel extraction are slightly sensitive to temperature but are pH dependent. Metal extraction equilibria are reached within about 5 min contact time. In addition, cobalt extraction depends on the extractant concentration in the organic phase. For a solution containing 0.5 g dm−3 each of cobalt and nickel and an initial pH of 4.1, conditions were established for the co‐extraction of both metals and selective stripping (with H2SO4) of cobalt and nickel. Using the appropriate reagent concentrations the yield (extraction stage) for both metals exceeded 90%, and stripping of cobalt and nickel was almost quantitative. Copyright © 2004 Society of Chemical Industry
Use of the radiation‐inducible WAF1 promoter to drive iNOS gene therapy as a novel anti‐cancer treatment
Authors: Worthington Jenny , McCarthy Helen O. , Barrett Eimear , Adams Catherine , Robson Tracy , Hirst David G
Published: April 2004

Background

Inducible nitric oxide synthase (iNOS) gene therapy has been identified as a potential anti‐tumour strategy. A major problem common to most gene therapy strategies is targeting of treatment to the tumour volume. In this study we report on the use of the X‐ray‐inducible WAF1 promoter to achieve targeting of iNOS expression to the tumour volume.

Methods

A WAF1/iNOS/liposome complex was injected directly into RIF‐1 and HT29 tumours in mice. A 4 Gy dose of X‐rays was applied to induce the WAF1 promoter followed, 8 h later, by treatment doses of 10 or 20 Gy. Tumour volume was measured, and growth curves plotted.

Results

Intra‐tumoural injection of WAF1/iNOS combined with a priming dose of X‐rays to induce the WAF1 promoter, followed by a treatment dose, resulted in sensitiser enhancement ratios of 2.0 and 1.3 in RIF‐1 and HT29 tumours, respectively, compared with radiation treatment alone. PCR analysis of organ tissue after intra‐tumoural injection of WAF1/iNOS showed that vector sequences were detected in all tissue tested; however, Western blot analysis revealed that iNOS protein levels were significantly increased only in tumour and the surrounding dermal tissue that had been exposed to the 4 Gy inducing dose.

Conclusions

iNOS gene therapy in combination with an inducible promoter results in significant tumour cell radiosensitisation. The WAF1 promoter may be a good candidate for a gene therapy as it is silent in normal tissue yet can be induced by the tumour environment. Copyright © 2004 John Wiley & Sons, Ltd.
Influence of “Alternative” C‐terminal amino acids on the formation of [b3 + 17 + Cat]+ products from metal cationized synthetic tetrapeptides
Authors: Anbalagan V. , Silva A. T. M. , Rajagopalachary S. , Bulleigh K. , Talaty E. R. , Van Stipdonk M. J.
Published: April 2004

The aim of this study was to investigate the dissociation patterns, and in particular the relative abundance of [b3 + 17 + Cat]+, for peptides with C‐termini designed to allow transfer of the —OH required to generate the product ion, but not necessarily as the most favored pathway. Working with the hypothesis that formation of a five‐membered ring intermediate, including intramolecular nucleophilic attack by a carbonyl oxygen atom, is an important mechanistic step, several model peptides with general sequence AcFGGX were synthesized, metal cationized by electrospray ionization and subjected to collision‐induced dissociation (CID). The amino acid at position X was one that either required a larger ring intermediate (β‐alanine, γ‐aminobutyric acid and ε‐amino‐n‐caproic acid to generate six‐, seven‐ or nine‐ membered rings, respectively) to transfer —OH, lacked a structural element required for nucleophilic attack (aminoethanol) or prohibited cyclization because of the inclusion of a rigid ring (p‐ and m‐aminobenzoic acid). For Ag+, Li+ and Na+ cationized peptides, our results show that amino acids requiring the adoption of larger ring intermediates suppressed the formation of [b3 + 17 + Cat]+, while amino acids that prohibit cyclization eliminated the reaction pathway completely. Formation of [b3 − 1 + Cat]+ from the alkali metal cationized versions was not a favorable process upon suppression or elimination of the [b3 + 17 + Cat]+ pathway: the loss of H2O to form [M − H2O + Cat]+ was instead the dominant dissociation reaction observed. Multiple‐stage dissociation experiments suggest that [M − H2O + Cat]+ is not [b4 − 1 + Cat]+ arising from the loss of H2O from the C‐terminus, but may instead be a species that forms via a mechanism involving the elimination of an oxygen atom from an amide group. Copyright © 2004 John Wiley & Sons, Ltd.
Lymnaea stagnalisand the development of neuroelectronic technologies
Authors: Birmingham John T. , Graham Dustin M. , Tauck David L.
Published: April 2004

The recent development of techniques for stimulating and recording from individual neurons grown on semiconductor chips has ushered in a new era in the field of neuroelectronics. Using this approach to construct complex neural circuits on silicon from individual neurons will require improvements at the neuron/semiconductor interface and advances in controlling synaptogenesis. Although devices incorporating vertebrate neurons may be an ultimate goal, initial investigations using neurons from the pond snailLymnaea stagnalishave distinct advantages. Simple two‐cell networks connected by electrical synapses have already been reconstructed on semiconductor chips. Furthermore, considerable progress has been made in controlling the processes that underlie chemical synapse formation inLymnaea. Studies ofLymnaeaneural networks on silicon chips will lead to a deeper understanding of the long‐term dynamics of simple neural circuits and may provide the basis for reliable interfaces for new neuroprosthetic devices. © 2004 Wiley‐Liss, Inc.
Overexpression of α‐synuclein decreased viability and enhanced sensitivity to prostaglandin E2, hydrogen peroxide, and a nitric oxide donor in differentiated neuroblastoma cells
Authors: Prasad Judith E. , Kumar Bipin , Andreatta Cynthia , Nahreini Piruz , Hanson Amy J. , Yan Xiang Dong , Prasad Kedar N.
Published: April 2004

Increased accumulation of α‐synuclein is associated with certain neurodegenerative diseases including Parkinson's disease (PD) and Alzheimer's disease (AD). One mechanism of α‐synuclein‐induced toxicity involves increased oxidative stress. It was unknown whether neurons overexpressing α‐synuclein would exhibit increased sensitivity to hydrogen peroxide (H2O2) or 3‐morpholinosydnonimine (SIN‐1; a nitrous oxide donor). To study this, we developed a murine neuroblastoma (NB) cell line that overexpresses wild‐type human α‐synuclein (NBP2‐PN54) under the control of the cytomegalovirus (CMV) promoter using a retroviral vector. Human α‐synuclein mRNA and protein were readily detectable in NBP2‐PN54 cells. Results showed that differentiated NBP2‐PN54 cells exhibited decreased viability in comparison to differentiated vector (NBP2‐PN1) and parent (NBP2) control cells. These cells also exhibited increased sensitivity to PGE2, H2O2 and SIN‐1. Because of involvement of proteasome inhibition in neurodegeneration, we also investigated whether treatment of differentiated NBP2‐PN54 cells with PGE2, H2O2 or SIN‐1 inhibits proteasome activity. Results showed that H2O2 and SIN‐1 inhibited proteasome activity, but PGE2 did not. These results suggest that overexpression of α‐synuclein not only participates directly in degeneration of neurons, but it also increases the vulnerability of neurons to other potential neurotoxins. © 2004 Wiley‐Liss, Inc.
Cloning and developmental expression of nonmuscle myosin IIA (Myh9) in the mammalian inner ear
Authors: Mhatre Anand N. , Li Jiang , Kim Yuil , Coling Donald E. , Lalwani Anil K.
Published: April 2004

MYH9 encoding a nonmuscle myosin heavy chain has been linked to nonsyndromic and syndromic forms of autosomal dominant hereditary hearing loss, suggesting a critical biological role of this motor protein in the auditory organ. While Myh9 expression has been described in the adult mouse, critical parameters pertaining to its developmental expression remain to be characterized. The current study describes cloning of the mouse Myh9 cDNA and the temporal onset and spatial distribution of Myh9 expression in the inner ear of the developing fetus, the neonate, and the adult. The cloned Myh9 cDNA contained two single‐base‐pair differences from the published genomic sequence: T990C (G330G) and T5198A (L1733Q). Immunoblotting of embryonic (E15.5) and adult tissues from several organs, including the cochlea, identified a single 250‐kDa anti‐Myh9‐immunoreactive band, supporting an absence of Myh9 splice variants in the fetus and the adult. In situ expression analysis identified Myh9 distributed within the epithelial layer of the otic vesicle at E10.5. Myh9 expression was found to persist within the epithelia surrounding the cochlear duct at E13.5 and E16.5. The sensory cells of the developing cochlea were positive for Myh9 expression at E16.5. Within the neonate and the adult cochlea, Myh9 expression was observed within the sensory hair cells and the supporting hair cells of the organ of Corti, the spiral ligament, and the spiral limbus, but not in the stria vascularis. Identification of Myh9 in the developing and mature inner ear suggests a role for this protein in the development and maintenance of auditory function. © 2004 Wiley‐Liss, Inc.
Protection against ischemic brain damage in rats by immunophilin ligand GPI‐1046
Authors: Li Feng , Omori Nobuhiko , Hayashi Takeshi , Jin Guang , Sato Keiko , Nagano Isao , Shoji Mikio , Abe Koji
Published: April 2004

To determine the effect of immunophilin ligand GPI‐1046 on ischemic brain injury, 90 min of transient middle cerebral artery occlusion (MCAO) was carried out in rat brains. In contrast to cases treated with vehicle, the infarct volume was reduced greatly and rotamase activity was inhibited significantly at 24 hr of reperfusion by treatment with GPI‐1046. Immunoreactivity and the number of cells stained positively for FKBP12, FKBP52, caspase‐8, cytochrome c, and caspase‐3 were also reduced markedly in the brain after GPI‐1046 treatment. The present results suggest that GPI‐1046 significantly decreased infarct volume and provided neuroprotective effect on rats after transient focal cerebral ischemia by inhibiting the increase of rotamase activity and of the number of FKBP12‐, FKBP52‐, caspase‐8‐, cytochrome c‐, and caspase‐3‐positive cells in the ischemic area. © 2004 Wiley‐Liss, Inc.