bluuebunny/crossref_metadata_2025 huggingface dataset:
Investment in a New Technology as a Signal of Firm Value Under Regulatory Opportunism
Authors: Spiegel Yossef , Wilkie Simon
Published: January 2005

We examine the question of whether a regulated firm that makes a long‐term investment in infrastructure can credibly signal its private information regarding the future demand for its output to the capital market. We show that necessary conditions for a separating equilibrium in which the magnitude of investment signals high future demand may include a low degree of managerial myopia, large variability of future demand, a lenient regulatory climate, and low sunk cost. Our model suggests that in estimating valuation models of regulated firms it is important to separate firms into two groups: firms for which a separating equilibrium is likely to obtain and firms for which the equilibrium is likely to be pooling. The market value of a firm in the first group is positively correlated with its level of investment, but uncorrelated with the level of actual demand, whereas for the second group the opposite holds.
Why Lever into a Zero‐Profit Industry: Tying, Foreclosure, and Exclusion
Authors: DeGraba Patrick
Published: January 2005

This paper considers the incentives of a firm with power in a market for one good to tie in the sale of a complementary good even though the complementary good is produced in a zero profit market. If the zero‐profit price of the tied good is greater than the marginal cost (which occurs for example when the technology is characterized by a fixed cost and a constant marginal cost), a firm will fie in order to increase the sales of the complementary good, which at the margin is profitable. We show that such tying will lower the effective prices paid by customers and increase welfare. This incentive exists if the firm with market power is a monopolist or one of several competing oligopolists.
U.S. Futures Exchanges Face“Mission Impossible”
Authors: Arbor Patrick H.
Published: January 2005

For U.S. futures exchanges, controlling costs while maintaining market performance is an ongoing, difficult challenge. New market realities have made that challenge even more daunting in recent years as costs have escalated, competition has expanded, and the role of information technology has expanded. It is always difficult for regulatory statutes to keep pace with ever‐changing markets. Futures markets are no exception. The basic statutory framework represented by the Commodity Exchange Act (CEA) was enacted in 1922, over seventy years ago. In order to maintain appropriate regulatory balance, periodic review and reform has been essential over the years. Our current federal regulatory systems were built for different markets with different competitive realities than we face today. Reforming the CEA to take into account those new market realities is vital to the survival of U.S. futures exchanges.
Most‐Favored‐Customer Clauses and Multilateral Contracting: When Nondiscrimination Implies Uniformity
Authors: DeGraba Patrick
Published: January 2005

DeGraba and Postlewaite (1992) show that the seller of a durable input can solve the time inconsistency problem by offering most‐favored‐customer (MFC) protection to buyers. McAfee and Schwartz (1994) show that if a supplier sells inputs to competing firms using two‐part tariffs, MFC protection that allows a firm to replace its contract with a contract executed by any other firm will not solve the commitment problem, and argue this implies managers cannot use MFCs as a strategic commitment device in complex contracting situations. This paper shows that if the profits of the seller and the buyers are monotonic in each term of the contract, then applying MFC protection to each term of a contract allows a manager to solve his commitment problem in complex contacting situations. We show that “standard” contract arrangements (two‐part tariffs, declining block tariffs, and royalties as a percentage of sales) meet this condition.
Morphological Changes in the Rat Endocrine Pancreas within 12 h of Intravenous Streptozotocin Administration
Authors: Nagasao J. , Yoshioka K. , Amasaki H. , Tsujio M. , Ogawa M. , Taniguchi K. , Mutoh K.
Published: January 2005

We examined early morphological changes in pancreatic endocrine cells within 12 h of intravenous streptozotocin (STZ) administration (60 mg/kg). Thirty rats were allocated either to a control group (vehicle alone) or to one of four experimental groups tested after 3, 6, 9 and 12 h. Karyopyknosis and cytoplasmic vacuoles were first observed in β‐cell cytoplasm 3 h after STZ administration (STZ‐3 h), and the most severe damage was found in β cells at STZ‐12 h. Insulin‐positive non‐islet cells were observed near the intercalated duct (ICD) and/or centroacinar (CA) cells at STZ‐6 h and their numbers peaked at STZ‐6 h. The distribution patterns of the insulin‐positive cells and those of nestin and insulin‐like growth factor‐1 were similar and their nuclei were positive for proliferating cell nuclear antigen. Thus, ICD cells and/or CA cells reacted immediately to transform into insulin‐secreting cells to replace injured β cells (or to compensate for the lack of β cells) within 12 h of STZ administration.
Congenital Duplication of the Caudal Region (Monocephalus Dipygus) in a Kid Goat
Authors: Corbera J. A. , Arencibia A. , Morales I. , Gutierrez C.
Published: January 2005

A case of congenital duplication (monocephalus dipygus) in a goat is described. Two pelvis and four pelvic limbs were observed in the kid. Conjoined or fused symmetric twins were diagnosed. Associated abnormalities were cleft palate and anal atresia. Most of the classically recognized teratogens were ruled out by history and serology. However, progenitors were related in the second degree. Thus, genetic factors could be suspected in this case. To the authors’ best knowledge, this is the first report of monocephalus dipygus in a goat.
Ultracytochemical Demonstration of Glycoproteins in the Eccrine Glands of the Digital Pads of the North American Raccoon (Procyon lotor)
Authors: Yasui T. , Tsukise A. , Meyer W.
Published: January 2005

In the eccrine glands of the digital pads of the North American raccoon (Procyon lotor), ultrastructural localization of glycoproteins with various saccharide residues was studied using preferably lectin cytochemical methods. Secretory granules observed in the dark cells exhibited glycoproteins with different terminal sugars (α‐d‐mannose, β‐d‐galactose, β‐N‐acetyl‐d‐glucosamine and sialic acid). The cytoplasm of the clear cells contained numerous glycogen particles. Several sugars were also detectable in the surface coat of the plasma membrane of the secretory cells. The results obtained could be helpful in understanding secretion production and cell related secretion functions of the eccrine glands of the raccoon digital foot pads.
The Role of Body Size in Mating Interactions of the Sexually Cannibalistic Fishing SpiderDolomedes triton
Authors: Johnson J. Chadwick
Published: January 2005

Some arachnids display extreme sexual size dimorphism (SSD) with adult females being several times larger than adult males. One explanation for SSD in species that exhibit pre‐copulatory sexual cannibalism (female attack, kill and consumption of the male prior to mating) is that smaller males may be less likely victims of predatory attacks by females. However, in some sexually cannibalistic species SSD is relatively moderate (i.e. males are similar in size to females) suggesting benefits of large male body size. Here, I report the results of an experiment designed to explore the ramifications of body size in mating interactions of the sexually cannibalistic, North American fishing spider (Dolomedes triton). Results suggest that male size does not influence courtship behavior, the likelihood of being attacked, or the male's ability to secure a mounting. However, large males were superior at gaining copulations once mounted. Sexual cannibalism may also be predicated on female size. Female condition (mass/cephalothorax area) did not explain any of these behaviors from the copulatory sequence, however, females with a smaller cephalothorax area were more likely to attack courting males. Finally, analysis of the ratio of female size to male size showed that when SSD is weak males are more likely to escape attacks and mate successfully. Results are discussed in light of several hypotheses for sexual cannibalism, and the benefits of large male body size illustrated here are put forth as potential explanations for the relatively moderate extent of SSD found in this sexually cannibalistic species.
Mammalian isovalthine metabolism
Authors: Rutherfurd‐Markwick K. J. , Rogers Q. R. , Hendriks W. H.
Published: January 2005

Isovalthine is a branched‐chain sulphur amino acid, which has been found in the urine of normal cats. The concentrations of isovalthine in the urine of healthy adult cats are approximately 24–66 μmol/l and are not affected by the gender of the cat. Isovalthinuria can be induced in other species (rats, rabbits, guinea‐pigs, humans, dogs) following the administration of certain inducing agents such as some hypocholesterolaemic agents, bile acids, hormones or cholesterol precursors. The method of induction of isovalthinuria was studied extensively during the 1960s, and efforts were made to understand its biosynthesis. However, although the origin of the sulphur atom in isovalthine was shown to be from cysteine or methionine, the origin of the carbon skeleton remains unknown. Interest in isovalthine metabolism was generated in part because it was reportedly found in the urine of patients with hypercholesterolaemia. The validity of this finding however, was brought into question following reports that administration of the drug Bromural (α‐bromoisovalerylurea), to humans results in the generation of compounds which break down to yield isovalthine following acid hydrolysis. This article presents a review and discussion of the experimental data on isovalthine metabolism.
Ascorbic acid concentrations in milk from Sudanese camels
Authors: Mohamed H. E. , Mousa H. M. , Beynen A. C.
Published: January 2005

The present study in Sudanese camels was done to describe the associations between vitamin C concentrations in milk, and either breed, stage of lactation, parity or the presence of mastitis. A total of 2586 camels were sampled. Arabi camels had higher ascorbic acid levels in milk than did either Anafi or Bishari camels. Milk ascorbic acid levels were higher for camels more than 180 days in lactation than for those earlier in lactation. Multiparous vs. primiparous camels had higher ascorbic acid concentrations in their milk. The ascorbic acid content of colostrum was higher than that of milk. Mastitis was associated with a decrease in the ascorbic acid content of both milk and blood plasma.
Respiratory infections during air travel
Authors: Leder K. , Newman D.
Published: January 2005

An increasing number of individuals undertake air travel annually. Issues regarding cabin air quality and the potential risks of transmission of respiratory infections during flight have been investigated and debated previously, but, with the advent of severe acute respiratory syndrome and influenza outbreaks, these issues have recently taken on heightened importance. Anecdotally, many people complain of respiratory symptoms following air travel. However, studies of ventilation systems and patient outcomes indicate the spread of pathogens during flight occurs rarely. In the present review, aspects of the aircraft cabin environment that affect the likelihood of transmission of respiratory pathogens on airplanes are outlined briefly and evidence for the occurrence of outbreaks of respiratory illness among airline passengers are reviewed. (Intern Med J 2005; 35: 50–55)
Modern management of portal hypertension
Authors: Lubel J. S. , Angus P. W.
Published: January 2005

The development of portal hypertension plays a major role in the pathogenesis of many of the complications of chronic liver disease. In developed countries, most patients with portal hypertension have cirrhosis, and, in this condition, portal pressure is elevated as a result of both an increase in hepatic resistance to portal perfusion and increased mesenteric blood flow. Bleeding from oesophageal varices is a major cause of mortality in patients with significant portal hypertension. This review concentrates on the recognition, prevention and acute management of this life threatening complication of cirrhosis. (Intern Med J 2005; 35: 45–49)
Outpatient treatment with subcutaneous interleukin‐2, interferon alpha and fluorouracil in patients with metastatic renal cancer: an Australian experience
Authors: Marx G. , Taylor J. , Goldstein D.
Published: January 2005

Background: Metastatic renal cell cancer has a poor prognosis and survival. Conventional cytotoxic chemotherapy has no impact on survival and response rates are low. Biologic agents are the most active in treating this disease. We report the feasibility of administering a combination of interferon alpha, subcutaneous interleukin‐2 and 5Fluorouracil in the outpatient setting to patients with metastatic renal cell cancer.

Results: Between September 1996 and August 2003, fourteen patients were treated with this combination: ten males and four females with a median age of 50 (42–66). Thirteen patients had Eastern Cooperative Oncology Group performance scores of 0 or 1. Ten patients had had nephrectomies. Six patients had undergone prior treatments with chemotherapy or hormonal therapy. Twenty‐two cycles were administered (median 1, range of 1–4). Three patients achieved partial response, eight patients had stable disease, and three had progressive disease. The duration of response in patients with stable disease was (3, 3+, 4, 4+, 5+, 6, 10, 11 months) and for the patients with a partial response was 2+, 11 and 12 months. Toxicities with this combination were predictable. There were no treatment‐related deaths and no episodes of febrile neutropenia. One patient ceased treatment as a result of toxicity. Fatigue was the most common side‐effect. Myalgias, fever and rigors occurred within 6–12 h of administration of interleukin‐2, and resolved within 12 h. Grade 1–2 nausea and vomiting occurred in most patients. Four patients had transient asymptomatic transaminitis, which resolved spontaneously. As a result of toxicity, one patient had treatment ceased in his 6th week.

Conclusion: This combination was feasible, well tolerated and manageable in an outpatient setting. (Intern Med J 2005; 35: 34–38)
A Random Variable Related to the Inversion Vector of a Partial Random Permutation
Authors: Laghate Kavita , Deshpande M. N.
Published: January 2005

In this article, we define the inversion vector of a permutation of the integers 1, 2, . . . , n. We set up a particular kind of permutation, called a partial random permutation. The sum of the elements of the inversion vector of such a permutation is a random variable of interest.
Neuronal death in primary retinal cultures is related to nitric oxide production, and is inhibited by erythropoietin in a glucose‐sensitive manner
Authors: Layton C. J. , Wood J. P. M. , Chidlow G. , Osborne N. N.
Published: January 2005

The aim of this work was to investigate the interrelated effects of glucose, nitric oxide (NO) and erythropoietin on neuronal survival in retinal cultures, thereby exploring the mechanism of neuronal death in the diabetic retina. Rat retinal cells were cultured in low (5 mm) or high (15 mm) glucose concentrations. After 9 days, cell viability was assessed by (3,4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide (MTT) assay and NO production was determined by the Griess reaction. Immunohistochemistry was used to quantify GABA‐labelled neurones and cells staining for DNA breakdown. High or low glucose concentrations had no effect on basal NO production or the survival of neurones in culture, but treatment with N‐nitro‐l‐arginine methyl ester reduced extracellular levels of NO and increased neuronal survival at both concentrations of glucose. Erythropoietin decreased cell death and NO levels, but only in cultures grown in low concentrations of glucose. It is concluded that erythropoietin's neurotrophic function in the retina is attenuated at glucose concentrations similar to those which occur in diabetes.
AG490 prevents cell death after exposure of rat astrocytes to hydrogen peroxide or proinflammatory cytokines: involvement of the Jak2/STAT pathway
Authors: Gorina Roser , Petegnief Valérie , Chamorro Ángel , Planas Anna M.
Published: January 2005

Janus kinases/STAT pathway mediates cellular responses to certain oxidative stress stimuli and cytokines. Here we examine the activation of Stat1 and Stat3 in rat astrocyte cultures and its involvement in cell death. H2O2, interferon (INF)‐γ and interleukin (IL)‐6 but not IL‐10 caused cell death. Stat1 was phosphorylated on tyrosine (Tyr)‐701 after exposure to H2O2, INF‐γ or IL‐6 but not IL‐10. Tyr‐705 pStat3 was observed after H2O2, IL‐6 and IL‐10. Also, H2O2induced serine (Ser)‐727 phosphorylation of Stat1 but not Stat3. The degree of Tyr‐701 pStat1 by the different treatments positively correlated with the corresponding reduction of cell viability. AG490, a Jak2 inhibitor, prevented Tyr‐701 but not Ser‐727, Stat1 phosphorylation. Also, AG490 inhibited Tyr‐705 Stat3 phosphorylation induced by H2O2and IL‐6 but did not prevent that induced by IL‐10. Furthermore, AG490 conferred strong protection against cell death induced by INF‐γ, IL‐6 and H2O2. These results suggest that Jak2/Stat1 activation mediates cell death induced by proinflammatory cytokines and peroxides. However, we found evidence suggesting that AG490 reduces oxidative stress induced by H2O2, which further shows that H2O2and/or derived reactive oxygen species directly activate Jak2/Stat1, but masks the actual involvement of this pathway in H2O2‐induced cell death.
Bi‐functional effects of ATP/P2 receptor activation on tumor necrosis factor‐alpha release in lipopolysaccharide‐stimulated astrocytes
Authors: Kucher Brandon M. , Neary Joseph T.
Published: January 2005

Neuroinflammation is associated with a variety of CNS pathologies. Levels of tumor necrosis factor‐alpha (TNF‐α), a major proinflammatory cytokine, as well as extracellular ATP, are increased following various CNS insults. Here we report on the relationship between ATP/P2 purinergic receptor activation and lipopolysaccharide (LPS)‐induced TNF‐α release from primary cultures of rat cortical astrocytes. Using ELISA, we confirmed that treatment with LPS stimulated the release of TNF‐α in a concentration and time dependent manner. ATP treatment alone had no effect on TNF‐α release. LPS‐induced TNF‐α release was attenuated by 1 mm ATP, a concentration known to activate P2X7 receptors. Consistent with this, 3′‐O‐(4‐Benzoyl)benzoyl‐ATP (BzATP), a P2X7 receptor agonist, also attenuated LPS‐induced TNF‐α release. This reduction in TNF‐α release was not due to loss of cell viability. Adenosine and 2‐chloroadenosine were ineffective, suggesting that attenuation of LPS‐induced TNF‐α release by ATP was not due to ATP breakdown and subsequent activation of adenosine/P1 receptors. Interestingly, treatment of astrocyte cultures with 10 µm or 100 µm ATP potentiated TNF‐α release induced by a submaximal concentration of LPS. UTP and 2methylthioADP (2‐MeSADP), P2Y receptor agonists, also enhanced this LPS‐induced TNF‐α release. Our observations demonstrate opposing effects of ATP/P2 receptor activation on TNF‐α release, i.e. P2X receptor activation attenuates, whereas P2Y receptor activation potentiates TNF‐α release in LPS‐stimulated astrocytes. These observations suggest a mechanism whereby astrocytes can sense the severity of damage in the CNS via ATP release from damaged cells and can modulate the TNF‐α mediated inflammatory response depending on the extracellular ATP concentration and corresponding type of astrocyte ATP/P2 receptor activated.
Co‐localization and functional interaction between adenosine A2A and metabotropic group 5 receptors in glutamatergic nerve terminals of the rat striatum
Authors: Rodrigues Ricardo J. , Alfaro Tiago M. , Rebola Nelson , Oliveira Catarina R. , Cunha Rodrigo A.
Published: January 2005

The anti‐Parkinsonian effect of glutamate metabotropic group 5 (mGluR5) and adenosine A2A receptor antagonists is believed to result from their ability to postsynaptically control the responsiveness of the indirect pathway that is hyperfunctioning in Parkinson's disease. mGluR5 and A2A antagonists are also neuroprotective in brain injury models involving glutamate excitotoxicity. Thus, we hypothesized that the anti‐Parkinsonian and neuroprotective effects of A2A and mGluR5 receptors might be related to their control of striatal glutamate release that actually triggers the indirect pathway. The A2A agonist, CGS21680 (1–30 nm) facilitated glutamate release from striatal nerve terminals up to 57%, an effect prevented by the A2A antagonist, SCH58261 (50 nm). The mGluR5 agonist, CHPG (300–600 μm) also facilitated glutamate release up to 29%, an effect prevented by the mGluR5 antagonist, MPEP (10 μm). Both mGluR5 and A2A receptors were located in the active zone and 57 ± 6% of striatal glutamatergic nerve terminals possessed both A2A and mGluR5 receptors, suggesting a presynaptic functional interaction. Indeed, submaximal concentrations of CGS21680 (1 nm) and CHPG (100 μm) synergistically facilitated glutamate release and the facilitation of glutamate release by 10 nm CGS21680 was prevented by 10 μm MPEP, whereas facilitation by 300 μm CHPG was prevented by 10 nm SCH58261. These results provide the first direct evidence that A2A and mGluR5 receptors are co‐located in more than half of the striatal glutamatergic terminals where they facilitate glutamate release in a synergistic manner. This emphasizes the role of the modulation of glutamate release as a likely mechanism of action of these receptors both in striatal neuroprotection and in Parkinson's disease.
Anesthesia and post‐mortem interval profoundly influence the regulatory serine phosphorylation of glycogen synthase kinase‐3 in mouse brain
Authors: Li Xiaohua , Friedman Ari B. , Roh Myoung‐Sun , Jope Richard S.
Published: January 2005

Glycogen synthase kinase‐3 (GSK3) is a crucial enzyme contributing to the regulation of neuronal structure, plasticity and survival, is implicated as a contributory factor in prevalent diseases such as Alzheimer's disease and mood disorders and is regulated by a wide range of signaling systems and pharmacological agents. Therefore, factors regulating GSK3 in vivo are currently of much interest. GSK3 is inhibited by phosphorylation of serine‐9 or serine‐21 in GSK3β and GSK3α, respectively. This study found that accurate measurements of phospho‐Ser‐GSK3 in brain are confounded by a rapid post‐mortem dephosphorylation, with ∼90% dephosphorylation of both GSK3 isoforms occurring within 2 min post‐mortem. Furthermore, three anesthetics, pentobarbital, halothane and chloral hydrate, each caused large in vivo increases in the serine phosphorylation of both GSK3β and GSK3α in several regions of mouse brain. Thus, studies of the phosphorylation state of GSK3 in brain, and perhaps in other tissues, need to take into account post‐mortem changes and the effects of anesthetics and there is a direct correlation between anesthesia and high levels of serine‐phosphorylated GSK3.
BAALC 1‐6‐8 protein is targeted to postsynaptic lipid rafts by its N‐terminal myristoylation and palmitoylation, and interacts with α, but not β, subunit of Ca2+/calmodulin‐dependent protein kinase II
Authors: Wang Xin , Tian Qing‐Bao , Okano Akira , Sakagami Hiroyuki , Moon Il Soo , Kondo Hisatake , Endo Shogo , Suzuki Tatsuo
Published: January 2005

We cloned a rat BAALC 1‐6‐8 isoform cDNA (GenBank™ Accession No. AB073318) that encoded a 22‐kDa protein, and identified endogenous BAALC 1‐6‐8 protein in the brain. The gene was expressed widely in the frontal part of the brain, and the protein was localized to the synaptic sites and was increased in parallel with synaptogenesis. The protein interacted with the α, but not β, subunit of Ca2+/calmodulin‐dependent protein kinase II (CaMKIIα). The interaction occurred between the N‐terminal 35‐amino‐acid region of BAALC 1‐6‐8 protein and the C‐terminal end of the regulatory domain of CaMKIIα, which contains α isoform‐specific sequence. Thus, the interaction may be CaMKIIα‐specific. We also found that BAALC 1‐6‐8 protein, as well as CaMKIIα, was localized to lipid rafts and that both myristoylation and palmitoylation of BAALC 1‐6‐8 N‐terminal portion were required for targeting of the protein into lipid rafts. These findings suggest that BAALC 1‐6‐8 protein play a synaptic role at the postsynaptic lipid raft possibly through interaction with CaMKIIα.
Brain‐derived neurotrophic factor prevents changes in Bcl‐2 family members and caspase‐3 activation induced by excitotoxicity in the striatum
Authors: Pérez‐Navarro Esther , Gavaldà Núria , Gratacòs Elena , Alberch Jordi
Published: January 2005

Brain‐derived neurotrophic factor (BDNF) prevents the loss of striatal neurons caused by excitotoxicity. We examined whether these neuroprotective effects are mediated by changes in the regulation of Bcl‐2 family members. We first analyzed the involvement of the phosphatidylinositol 3‐kinase/Akt pathway in this regulation, showing a reduction in phosphorylated Akt (p‐Akt) levels after both quinolinate (QUIN, an NMDA receptor agonist) and kainate (KA, a non‐NMDA receptor agonist) intrastriatal injection. Our results also show that Bcl‐2, Bcl‐xL and Bax protein levels and heterodimerization are selectively regulated by NMDA and non‐NMDA receptor stimulation. Striatal cell death induced by QUIN is mediated by an increase in Bax and a decrease in Bcl‐2 protein levels, leading to reduced levels of Bax:Bcl‐2 heterodimers. In contrast, changes in Bax protein levels are not required for KA‐induced apoptotic cell death, but decreased levels of both Bax:Bcl‐2 and Bax:Bcl‐xL heterodimer levels are necessary. Furthermore, QUIN and KA injection activated caspase‐3. Intrastriatal grafting of a BDNF‐secreting cell line counter‐regulated p‐AKT, Bcl‐2, Bcl‐xL and Bax protein levels, prevented changes in the heterodimerization between Bax and pro‐survival proteins, and blocked caspase‐3 activation induced by excitotoxicity. These results provide a possible mechanism to explain the anti‐apoptotic effect of BDNF against to excitotoxicity in the striatum through the regulation of Bcl‐2 family members, which is probably mediated by Akt activation.
S100B‐induced microglial and neuronal IL‐1 expression is mediated by cell type‐specific transcription factors
Authors: Liu Ling , Li Yuekui , Van Eldik Linda J. , Griffin W. Sue T. , Barger Steven W.
Published: January 2005

Both the astrocytic cytokine S100B and the pro‐inflammatory interleukin‐1 (IL‐1) are elevated in Alzheimer's disease, and each has been implicated in Alzheimer‐related neuropathology. We examined the gene‐regulatory events through which S100B induces IL‐1β expression. In primary microglia, S100B activated the transcription factors Sp1 and NFκB, followed by an increase in IL‐1β mRNA levels. The latter was blocked by a peptide inhibitor of NFκB or by a double‐stranded oligonucleotide containing a NFκB‐binding site to serve as ‘decoy’ DNA and reduce available NFκB. But in primary cortical neurons, decoy and siRNA experiments indicated that the IL‐1β induction by S100B was mediated by Sp1 without evidence of a role for NFκB. Our results suggest that the elevation of S100B and IL‐1 in Alzheimer brain and consequent neurodegenerative events are mediated through cell‐type specific gene‐regulatory events, providing mechanistic insight into connections between glial activation and neuronal dysfunction.
Effects of brain‐derived neurotrophic factor (BDNF) on glial cells and serotonergic neurones during development
Authors: Djalali S. , Höltje M. , Große G. , Rothe T. , Stroh T. , Große J. , Deng D. R. , Hellweg R. , Grantyn R. , Hörtnagl H. , Ahnert‐Hilger G.
Published: January 2005

Serotonergic neurones are among the first to develop in the central nervous system. Their survival and maturation is promoted by a variety of factors, including serotonin itself, brain‐derived neurotrophic factor (BDNF) and S100β, an astrocyte‐specific Ca2+ binding protein. Here, we used BDNF‐deficient mice and cell cultures of embryonic raphe neurones to determine whether or not BDNF effects on developing serotonergic raphe neurones are influenced by its action on glial cells. In BDNF–/– mice, the number of serotonin‐immunoreactive neuronal somata, the amount of the serotonin transporter, the serotonin content in the striatum and the hippocampus, and the content of 5‐hydroxyindoleacetic acid in all brain regions analysed were increased. By contrast, reduced immunoreactivity was found for myelin basic protein (MBP) in all brain areas including the raphe and its target region, the hippocampus. Exogenously applied BDNF increased the number of MBP‐immunopositive cells in the respective culture systems. The raphe area displayed selectively reduced immunoreactivity for S100β. Accordingly, S100β was increased in primary cultures of pure astrocytes by exogenous BDNF. In glia‐free neuronal cultures prepared from the embryonic mouse raphe, addition of BDNF supported the survival of serotonergic neurones and increased the number of axon collaterals and primary dendrites. The latter effect was inhibited by the simultaneous addition of S100β. These results suggest that the presence of BDNF is not a requirement for the survival and maturation of serotonergic neurones in vivo. BDNF is, however, required for the local expression of S100β and production of MBP. Therefore BDNF might indirectly influence the development of the serotonergic system by stimulating the expression of S100β in astrocytes and the production MBP in oligodendrocytes.
Coordinating Service‐Sensitive Demand and Capacity by Adaptive Decision Making: An Application of Case‐Based Decision Theory*
Authors: Jahnke Hermann , Chwolka Anne , Simons Dirk
Published: January 2005

The subject of this article is the simultaneous choice of product price and manufacturing capacity if demand is stochastic and service‐level sensitive. In this setting, capacity as well as price have an impact on demand because several aspects of service level depend on capacity. For example, delivery time will be reduced if capacity is increased given a constant demand rate. We illustrate the relationship between service level, capacity, and demand reaction by a stylized application problem from the after‐sales services industry.

The reaction of customers to variations in service level and price is represented by a kinked price‐demand‐rate function. We first derive the optimal price‐capacity combination for the resulting decision problem under full information. Subsequently, we focus on a decision maker (DM) who lacks complete knowledge of the demand function. Hence the DM is unable to anticipate the service level and consequently cannot identify the optimal solution. However, the DM will acquire additional information during the sales process and use it in subsequent revisions of the price‐capacity decision. Thus, this decision making is adaptive and based on experience. In contrast to the literature, which assumes certain repetitive procedures somewhat ad hoc, we develop an adaptive decision process based on case‐based decision theory (CBDT) for the price‐capacity problem. Finally, we show that a CBDT DM in our setting eventually finds the optimal solution, if the DM sets the price based on absorption costs and adequately adjusts the capacity with respect to the observed demand.
Acquisition of Telecommunications Bandwidth Under Economies of Scale in Size and Duration of Contracts*
Authors: Khouja Moutaz , Kumar Ram L.
Published: January 2005

Significant advances in information technology have brought about increased demand for bandwidth. Buyers of bandwidth often encounter bandwidth prices that are decreasing over time. Additionally, bandwidth prices at any point in time are decreasing in total bandwidth purchased and length of contracts. Therefore, buyers face complex decisions in terms of the number of contracts to buy, their bandwidth, and their lengths. In this article, we formulate models for the acquisition of bandwidth from a buyer's perspective. We begin with a model that allows varying contract durations under deterministic demand and without allowing shortages or overlapping contracts. We then formulate a simpler model, which restricts contract lengths over the planning horizon to be equal. We also solve the problem under probabilistic demand and allowing for shortages, which are satisfied by buying additional bandwidth at a premium. We perform numerical sensitivity analysis to compare the results of the models and illustrate the results with numerical examples. The numerical analyses illustrate that using relatively simple equal‐length contracts produces approximately the same results as the more complicated unequal‐length contract strategy.
Predicting System Usage from Intention and Past Use: Scale Issues in the Predictors
Authors: Kim Sung S. , Malhotra Naresh K.
Published: January 2005

The objective of this study is to provide insights into how the predictive power for computer‐recorded system usage can be improved. Based on 386 responses from actual users of an information system, we examine the predictive power for system usage according to the scales of the predictors used, namely, intention and past use. First, we show that the predictive power of intention can be significantly improved with the choice of an appropriate measure. However, even the desirable intention measure failed to explain two‐thirds of the variance in system usage. Second, the results show that past use as measured by computer‐recorded log data can significantly enhance our ability to predict system usage. Finally, when both intention and past use are controlled for, the explained variance in system usage is shown to vary widely from 20% to 73%, depending on the predictors' scales. Overall, our findings suggest that an accurate prediction of system usage requires a more rigorous approach than that often applied in information systems research.
Heart Rate Variability Fraction—A New Reportable Measure of 24‐Hour R‐R Interval Variation
Authors: Sosnowski Maciej , Clark Elaine , Latif Shahid , Macfarlane Peter W. , Tendera Michal
Published: January 2005

Background: The scatterplot of R‐R intervals has several unique features. Its numerical evaluation may produce a new useful index of global heart rate variability (HRV) from Holter recordings.

Methods: Two‐hundred and ten middle‐aged healthy subjects were enrolled in this study. The study was repeated the next day in 165 subjects. Each subject had a 24‐hour ECG recording taken. Preprocessed data were transferred into a personal computer and the standard HRV time‐domain indices: standard deviation of total normal R‐R intervals (SDNN), standard deviation of averaged means of normal R‐R intervals over 5‐minute periods (SDANN), triangular index (TI), and pNN50 were determined. The scatterplot area (0.2–1.8 second) was divided into 256 boxes, each of 0.1‐second interval, and the number of paired R‐R intervals was counted. The heart rate variability fraction (HRVF) was calculated as the two highest counts divided by the number of total beats differing from the consecutive beat by <50 ms. The HRVF was obtained by subtracting this fraction from 1, and converting the result to a percentage.

Results: The normal value of the HRVF was 52.7 ± 8.6%. The 2–98% range calculated from the normal probability plot was 35.1–70.3%. The HRVF varied significantly with gender (female 48.7 ± 8.4% vs male 53.6 ± 8.6%, P = 0.002). The HRVF correlated with RRI (r = 0.525) and showed a similar or better relationship with SDNN (0.851), SDANN (0.653), and TI (0.845) than did the standard HRV measures with each other. Bland‐Altman plot showed a good day‐by‐day reproducibility of the HRVF, with the intraclass correlation coefficient of 0.839 and a low relative standard error difference (1.8%).

Conclusion: We introduced a new index of HRV, which is easy for computation, robust, reproducible, easy to understand, and may overcome the limitations that belong to the standard HRV measures. This index, named HRV fraction, by combining magnitude, distribution, and heart‐rate influences, might become a clinically useful index of global HRV.
Electrocardiographic T‐ and U‐Wave Discordance
Authors: Reinig Michael G. , Harizi Robert , Spodick David H.
Published: January 2005

Background: Abundant information has been reported regarding the U wave, which almost entirely has been focused on U waves in isolation. There has been little investigation of discordant T and U waves.

Methods: Of 18,750 consecutively recorded electrocardiograms, 143 patients were categorized resulting in three groups. Group A: 53 patients with negative T waves and positive U waves (Type I Discordance); Group B: 26 patients with positive T waves and negative U waves (Type II Discordance); and Group C: 63 patients with negative T and negative U waves. Each patient's chart was reviewed for relevant clinical, laboratory, and medical history.

Results: Coronary disease was slightly more common in Group A (64%) than in Group B (46%) (P = 0.174; ns). Coronary disease in Group C was extremely common (88%; P <0.001). Hypertension in the two discordant groups was similar: Group A (60%) versus Group B (58%) (P = ns), Group C was significantly higher (88%) (P <0.001). Left ventricular hypertrophy was 49% in Group A and 58% in Group B (P = ns), but Group C was significantly higher at 70% (P = 0.038).

Conclusions: This appears to be the first investigation of the associations of discordant T and U waves. We found that the significance of any U wave is not independent of their respective T wave. In addition, we propose that the U wave not be analyzed in isolation, but rather with respect to its T wave.
Surface Electrocardiography and Histologic Rejection Following Orthotopic Heart Transplantation*
Authors: Eckart Robert E. , Kolasa Mark W. , Khan Nancy A. , Kwan Michael D. , Peele Mark E.
Published: January 2005

Background: Intraventricular conduction delay and QT interval dispersion may be related to electrical instability and the risk of ventricular arrhythmogenesis. The interlead variability of the QT interval on a surface 12‐lead electrocardiogram (ECG) has been associated with an increased likelihood of sudden death in patients with long QT syndromes, in patients recovering from myocardial infarction, and dilated cardiomyopathy. We sought to determine the incidence of increased QTc dispersion (QTc‐d) relative to biopsy grade of severity of rejection.

Methods: Records of patients having undergone orthotopic heart transplantation (OHT) were reviewed focusing specifically on surface ECGs performed in temporal proximity to endomyocardial biopsy.

Results: Seventy‐five patients were evaluated on 1573 occasions, to include 999 surface ECGs, and 847 endomyocardial biopsies. There were 269 interpretable surface ECGs and endomyocardial biopsies performed within 1.1 ± 4.6 days. There were no identifiable trends in atrioventricular or intraventricular conduction abnormalities (to include right bundle branch block) when comparing those with and without significant rejection on endomyocardial biopsy. The mean QTc‐d of those with none (n = 34), mild (n = 194), moderate (n = 39), and severe (n = 2) rejection was 49 ± 29, 49 ± 35, 57 ± 38, 81 ± 7 ms, respectively (P = 0.28 by ANOVA of means). When comparing those with significant rejection so as to change management there was a trend toward increased dispersion (no to mild rejection, 49 ± 34 ms vs moderate to severe rejection, 59 ± 37 ms, P = 0.09).

Conclusions: In this study investigating noninvasive ventricular depolarization/repolarization and correlation to histologic manifestation of rejection, there was suggestion, but no statistical significance, of QTc‐d and severity of rejection. QTc‐d should not be considered a sensitive marker for OHT rejection.
Heart Rate Variability: Measurement and Clinical Utility
Authors: Kleiger Robert E. , Stein Phyllis K. , Bigger J. Thomas
Published: January 2005

Electrocardiographic RR intervals fluctuate cyclically, modulated by ventilation, baroreflexes, and other genetic and environmental factors that are mediated through the autonomic nervous system. Short term electrocardiographic recordings (5 to 15 minutes), made under controlled conditions, e.g., lying supine or standing or tilted upright can elucidate physiologic, pharmacologic, or pathologic changes in autonomic nervous system function. Long‐term, usually 24‐hour recordings, can be used to assess autonomic nervous responses during normal daily activities in health, disease, and in response to therapeutic interventions, e.g., exercise or drugs. RR interval variability is useful for assessing risk of cardiovascular death or arrhythmic events, especially when combined with other tests, e.g., left ventricular ejection fraction or ventricular arrhythmias.
Noninvasive Sudden Death Risk Stratification by Ambulatory ECG‐Based T‐Wave Alternans Analysis: Evidence and Methodological Guidelines
Authors: Verrier Richard L. , Nearing Bruce D. , Kwaku Kevin F.
Published: January 2005

Extensive experimental and clinical evidence supports the utility of T‐wave alternans (TWA) as a marker of risk for ventricular fibrillation. This entity appears to reflect the fundamental arrhythmogenic property of enhanced dispersion of repolarization. This relationship probably accounts for its relative ubiquity in patients with diverse types of cardiac disease, as has been recognized with the development of analytical tools. A basic premise of this review is that ambulatory ECG monitoring of TWA as patients experience the provocative stimuli of daily activities can expose latent electrical instability in individuals at heightened risk for arrhythmias. We will discuss the literature that supports this concept and summarize the current state of knowledge regarding the use of routine ambulatory ECGs to evaluate TWA for arrhythmia risk stratification. The dynamic, nonspectral modified moving average analysis method for assessing TWA, which is compatible with ambulatory ECG monitoring, is described along with methodological guidelines for its implementation. Finally, the rationale for combined monitoring of autonomic markers along with TWA will be presented.
Design of functional coatings
Authors: Hegemann D. , Oehr C. , Fischer A.
Published: January 2005

Based on the principle of macroscopic kinetics, we present the concept of a standard process to compare different rf plasma reactors. Therefore, the mass deposition rate of pure hexamethyldisiloxane (HMDSO) discharges was chosen, since the plasma polymerization of HMDSO is a radical-dominated process and ion-induced effects can be neglected for a wide parameter range. Two experimental series with pure HMDSO discharges were performed within a symmetrical and a strongly asymmetrical rf plasma reactor. The obtained deposition rates were compared to four experimental series taken out of the literature concerning the deposition rates of plasma polymerized HMDSO coatings. While for each reactor design, the “specific energy” W∕F was found to describe the deposition rates very well, different apparent activation energies Ea were obtained. To bring the data sets into agreement, a new process constant Eadact is introduced taking the width of the active plasma zone dact into account. By this means, functionally gradient SiOC:H films can be designed, e.g., for adhesion, wetting, or barrier improvements. Moreover, processes can be optimized and scaled up.
Design and construction of a semiautomatic temperature programmed desorption apparatus for ultrahigh vacuum
Authors: Kondratyuk Petro , Yates John T.
Published: January 2005

A computer-controlled system that allows acquisition of large volumes of temperature programmed desorption data under ultrahigh vacuum conditions has been designed and tested. The vacuum part of the system consists of a sample mounted on a rotation–translation manipulator, a shielded quadrupole mass spectrometer for the desorption flux measurement, and a collimated molecular beam doser for adsorbate delivery. The experiment involves a series of tasks: (1) dosing of the adsorbate onto the surface; (2) calibration of the mass spectrometer gain; (3) translating the dosed sample to the mass spectrometer position; (4) linearly ramping the temperature of the sample to acquire the desorption spectrum; and (5) cooling the sample. In the system described here, these tasks are accomplished automatically. As a result, the time needed for the experiment and the potential for operator errors are substantially reduced. The performance of the system is demonstrated for CCl4 adsorbed on gold-supported single wall carbon nanotubes.
Ionization of sputtered metals in high power pulsed magnetron sputtering
Authors: Bohlmark Johan , Alami Jones , Christou Chris , Ehiasarian Arutiun P. , Helmersson Ulf
Published: January 2005

The ion to neutral ratio of the sputtered material have been studied for high power pulsed magnetron sputtering and compared with a continuous direct current (dc) discharge using the same experimental setup except for the power source. Optical emission spectroscopy (OES) was used to study the optical emission from the plasma through a side window. The emission was shown to be dominated by emission from metal ions. The distribution of metal ionized states clearly differed from the distribution of excited states, and we suggest the presence of a hot dense plasma surrounded by a cooler plasma. Sputtered material was ionized close to the target and transported into a cooler plasma region where the emission was also recorded. Assuming a Maxwell–Boltzmann distribution of excited states the emission from the plasma was quantified. This showed that the ionic contribution to the recorded spectrum was over 90% for high pulse powers. Even at relatively low applied pulse powers, the recorded spectra were dominated by emission from ions. OES analysis of the discharge in a continuous dc magnetron discharge was also made, which demonstrated much lower ionization.