bluuebunny/crossref_metadata_2025 huggingface dataset:
Dystonic Posturing Associated with Putaminal Hyperperfusion Depicted on Subtraction SPECT
Authors: Mizobuchi Masahiro , Matsuda Kazumi , Inoue Yushi , Sako Kazuya , Sumi Yoshihiro , Chitoku Shiro , Tsumaki Katsumi , Takahashi Masaaki
Published: July 2004

Summary:  Purpose: Dystonic posturing (DP) is one of the most reliable lateralizing indicators for temporal lobe epilepsy (TLE). We evaluated the ictal hyperperfusional areas in patients with DP by using ictal–interictal subtraction single‐photon emission computed tomography (SPECT).

Methods: Ninety‐seven patients were treated surgically for intractable TLE, and 39 patients underwent ictal and interictal SPECT studies with the same isotope. These patients were divided into three groups: group I with DP of the contralateral side extended to the epileptogenic focus, group II with elevated muscle tonus but without DP, and group III without DP or alteration of muscle tonus. Ictal, interictal SPECT and thin‐slice magnetic resonance imaging (MRI) were overlaid by using the automatic multimodality registration program to construct ictal–interictal subtracted images of SPECT on MRI.

Results: Thirteen patients belonged to group I; 14, to group II; and 12, to group III. A statistically significant difference in hyperperfusion rate was observed in the putamen (10 patients in group I, three in group II and two in group III; p < 0.01) and mesial temporal lobe (10 patients in group I, seven in group II, and two in group III; p < 0.05) on the ipsilateral side of the epileptogenic focus. No statistically significant difference was observed for other ictal symptoms except ipsilateral upper‐limb automatism (eight patients in group I, three in group II, and none in group III; p < 0.01).

Conclusions: A strong correlation between DP and hyperperfusion in the putamen and mesial temporal lobe was demonstrated. Some patients showed a wide hyperperfusion area extending from the mesial temporal lobe to putamen, which may correspond to the propagation of epileptic discharges. Our results suggest a correlation between hyperperfusion of putamen and contralateral dystonic posturing.
Evaluating the Utility of Inpatient Video‐EEG Monitoring
Authors: Ghougassian Daniel F. , D'Souza Wendyl , Cook Mark J. , O'Brien Terence J.
Published: July 2004

Summary:  Purpose: Inpatient video‐EEG monitoring (VEM) is widely used for the diagnosis, seizure classification, and presurgical evaluation of patients with seizure disorders. It is resource intensive and relatively expensive, so its utility continues to be debated. Few studies have specifically evaluated the utility of inpatient VEM in altering diagnosis or management of patients with seizure disorders. We sought to assess the proportion of patients for whom the preadmission diagnosis and management were altered after inpatient VEM of patients admitted for diagnostic and presurgical evaluation of seizure disorders.

Methods: Data from a consecutive cohort of patients admitted over a 3‐year period to an inpatient VEM unit in a tertiary referral hospital were retrospectively analyzed. The preadmission diagnosis and management by the referring neurologist was compared with the diagnosis and management after the VEM.

Results: Of 131 patients, 91 (70%) were admitted for diagnostic evaluation and 39 (30%) for a presurgical workup. Mean evaluative period was 5.6 days. Mean number of seizures recorded was 2.9. No seizures were recorded in 31% of patients. Interictal EEG showed epileptiform changes in 56 (43%). In 76 (58%), the diagnosis was altered as a result of the VEM, with the greatest change being an increase in the nonepileptic diagnosis group (7% to 31%) and the generalized diagnosis group (5% to 11%). Management was changed after the VEM in 95 (73%).

Conclusions: The results of this study demonstrate that inpatient VEM has a high yield in changing diagnosis and management. Future long‐term cost–benefit studies of the management changes resulting from VEM evaluation will aid in further reinforcing its role.
Treatment of Refractory Status Epilepticus with Hemispherectomy
Authors: Duane Dawn C. , Ng Yu‐tze , Rekate Harold L. , Chung Steve , Bodensteiner John B. , Kerrigan John F.
Published: July 2004

Summary: A 7‐year‐old boy with left hemiparesis secondary to right hemispheric cortical dysplasia was admitted to the hospital with increasing numbers of seizures. Magnetic resonance imaging showed a small dysplastic right hemisphere with abnormally thickened gyri and an apparently normal left hemisphere. Previous video‐electroencephalogram (EEG) monitoring showed bilateral independent spikes and generalized slow spike‐and‐wave episodes on EEG and [18F]fluorodeoxyglucose (FDG) positron emission tomography scan demonstrated scattered areas of regional hypometabolism bilaterally; therefore hemispherectomy was not undertaken at that time. During this hospital stay, nonconvulsive status epilepticus developed and was refractory to multiple medical therapies including pentobarbital (PTB) coma. Burst‐suppression pattern during PTB coma appeared to be generalized spike and wave, but when EEG was reviewed with increased time resolution spikes suggested a right hemisphere origin. The patient underwent bilateral intracarotid amobarbital spike‐suppression test that showed only minimal suppression of epileptiform discharges with injection of the left carotid, but complete suppression of spike activity after right‐sided carotid injection. A right hemispherectomy was performed with complete cessation of status epilepticus. Postoperative EEG showed no epileptiform discharges. Patient follow‐up was limited to 12 months after surgery. The patient had regained the ability to walk unaided and was seizure free with a single antiepileptic medication. This case illustrates a potentially life‐saving procedure for refractory status epilepticus and several techniques including a spike‐suppression test to aid in prediction of cessation of seizures after hemispherectomy.
Prescience as an Aura of Temporal Lobe Epilepsy
Authors: Sadler and R. Mark , Rahey Susan
Published: July 2004

Summary:  Purpose: A patient with a distinct aura of prescience as a manifestation of temporal lobe epilepsy was encountered. The experience prompted a review of this ictal phenomenon among patients attending a tertiary care epilepsy outpatient clinic.

Methods: A computer epilepsy database was searched for patients with simple partial sensory seizures and complex partial seizures with auras. Identified patients had charts reviewed for details of the auras; patients were contacted and asked to provide written descriptions of their experiences. Literature searches (PubMed) were done by using the terms “precognition” or “prescience” and “seizures” or “epilepsy.” Standard comprehensive epilepsy textbooks were reviewed.

Results: The charts of 218 patients were reviewed from 927 in the database; three had prescience as an ictal feature. The patients' descriptions were very similar in all cases (a profound sense of “knowing” what was going to happen in their environment in the immediate future). The experience was distinct from déjà vu and other psychic experiences. All patients probably have temporal lobe epilepsy. Only one other description of prescience as an ictal feature was found in the literature.

Conclusions: Prescience can occur as an ictal feature of temporal lobe epilepsy and represents a previously underreported psychic phenomenon. The potential lateralizing value of this symptom is yet to be determined.
Optical properties of hair: detailed examination of specular reflection patterns in various hair types
Authors: McMullen R. , Jachowicz J.
Published: July 2004

Details of the specular reflection of curved hair tresses, resulting from illumination with a collimated incident light source, were examined both qualitatively and quantitatively using high‐resolution photography and image analysis. The reflections were found to consist of a multitude of light dots aligned with the fibers and typically separated by a distance of 81–145 μm. The contrast between the dots (specular reflection) and the darker regions (diffuse reflection) of the entire reflection band was found to increase with increasing pigmentation of hair. Highly pigmented Oriental hair provided more contrast within the specular reflection band than unpigmented natural white hair. A quantitative description of the light reflection patterns within the specular reflection band included two‐dimensional distribution of luminosity, histograms of the frequency of appearance for peak maxima and minima in luminosity distribution plots, and histograms of absolute maxima and minima of luminosity along the length of the fibers. Specular reflection from African hair, which consists of many curls that provide multiple and randomly distributed reflection centers, have also been investigated. Using microscopy software, image tool2.0, and a method termed image threshold, the number of reflection sites and their shapes could be quantified. For example, treatment of African hair with synthetic sebum was shown to significantly affect the reflection patterns, resulting in a decrease in the overall hair luster. Comparison of reflection patterns from Caucasian frizzy, very curly, and curly hair is also discussed.
Assessment and monitoring of damage from insects in Australian eucalypt forests and commercial plantations
Authors: Stone Christine , Coops Nicholas C
Published: July 2004

Abstract  This paper presents a review of recent developments in the assessment and monitoring of health in Australian eucalypt forests and plantations of pine and eucalypt species, with an emphasis on damage caused by herbivorous insects. The diverse range of interests and priorities amongst Australian stakeholders of native forests and plantations influences the scale, resolution and accuracy of results sought, and this in turn influences how the assessment data are collected, analysed and reported. The authors discuss sampling systems that include extensive ground‐based surveys, permanent plots and airborne technologies being developed in Australia. In all cases, there is an appreciation that the assessment protocols should be objective, repeatable and cost effective. Significant progress has been made in the application of digital, remotely sensed imagery to detect and classify damaged forest canopies. The success of this approach depends, in part, on a sound understanding of the progression of symptoms at the leaf, tree crown and stand scale, especially those symptoms that influence spectral reflectance behaviour.
Management of threatened insect species in Australia, with particular reference to butterflies
Authors: New Tim R , Sands Don P A
Published: July 2004

Abstract  Advances in determination of conservation status of insects through evaluation of threats (rather than simple ‘rarity’ alone) help to set priorities for allocation of conservation resources, and formulate effective legislative treatment and field management for the most needy species. Summaries of several recent conservation studies on butterflies exemplify the variety of practical needs, amongst which habitat protection and enhancement is paramount. However, the paucity of biological and distributional information on most Australian insects necessitates considerable flexibility in approach, so that perceptions of conservation need may be highly subjective. Listing species for protection and conservation priority must be viewed as a dynamic process, with opportunity for rapid action, either to list or de‐list taxa as research and recovery actions lead to change in perceived or real status and conservation need.
Quarantine – Phytosanitary, sanitary and incursion management: an Australian entomological perspective
Authors: Maynard Glynn V , Hamilton J Graeme , Grimshaw Judy F
Published: July 2004

Abstract  Insects challenge our international and interstate borders continually both by natural movement and by human assisted means. Insects are highly motile with a vast array of sensory organs that enable them to disperse and find hosts, hence they cause significant problems when introductions into new areas occur. A broad range of entomological skills, including ecology, diagnostics and pest management, is required to manage the quarantine, phytosanitary and incursion issues related to insects. These provide input into the regulatory framework and form a scientific basis for decision‐making processes. Phytosanitary measures are developed with scientific input, whereas the application of them is in a regulatory and legal environment.
Risk factors for hypospadias in Norwegian boys – association with testicular dysgenesis syndrome?
Authors: Aschim Elin Leirvoll , Haugen Trine B. , Tretli Steinar , Daltveit Anne Kjersti , Grotmol Tom
Published: July 2004

It has been proposed that hypospadias, cryptorchidism and testicular cancer, as well as decreasing sperm quality are symptoms of an underlying entity called testicular dysgenesis syndrome (TDS). We wanted to study the risk factors for hypospadias and compare them with those of the other conditions belonging to TDS. A large case–control study was undertaken on data on all live‐born boys registered in the Medical Birth Registry of Norway during the period 1967–1998 (n = 961 396; hypospadias cases = 2382). Logistic regression analysis was used to study the association between potential risk factors and hypospadias, estimated by odds ratio (OR). The risk factors for hypospadias were divided into four categories: (i) maternal characteristics, e.g. low parity [p(trend) < 0.001], hypertension (OR = 1.49) and bleeding (OR = 1.39) during index pregnancy, and (pre)eclampsia (OR = 1.84); (ii) complications during delivery, e.g. retained placenta (OR = 1.67) or Caesarean section (OR = 1.36); (iii) characteristics of the newborn, e.g. low birth weight [p(trend) < 0.001], small for gestational age (OR = 2.16), and presence of congenital malformations other than hypospadias (OR = 2.72), e.g. inguinal hernia (OR = 5.65); (iv) prevalence among relatives of hypospadias cases, e.g. brother with hypospadias (OR = 20.81). The novel finding of retained placenta as a risk factor indicates that early malfunction of placenta could be a causative factor for hypospadias. When comparing with previously published risk factors for hypospadias, cryptorchidism and testicular cancer, we found that the following risk factors were common to all three conditions: low parity, low birth weight, low gestational age, inguinal hernia, bleeding during pregnancy and Caesarean section. In conclusion, our results support the notion that the conditions of TDS share risk factors.
EAA/EMQN best practice guidelines for molecular diagnosis of y‐chromosomal microdeletions. State of the art 2004
Authors: Simoni M. , Bakker E. , Krausz C.
Published: July 2004

Microdeletions of the Y chromosome are the second most frequent genetic cause of spermatogenetic failure in infertile men after the Klinefelter syndrome. The molecular diagnosis of Y‐chromosomal microdeletions is routinely performed in the workup of male infertility in men with azoospermia or severe oligozoospermia. Since 1999, the European Academy of Andrology (EAA) and the European Molecular Genetics Quality Network (EMQN) support the improvement of the quality of the diagnostic assays by publication of the laboratory guidelines for molecular diagnosis of Y‐chromosomal microdeletions and by offering external quality assessment trials. The present revision of the 1999 laboratory guidelines summarizes the results of a ‘Best Practice Meeting’ held in Florence (Italy) in October 2003. The basic protocol for microdeletion screening suggested in the 1999 guidelines proved to be very accurate, sensitive and robust. In the light of the recent advance in the knowledge of the Y chromosome sequence and of the mechanism of microdeletion it was agreed that the basic 1999 protocol, based on two multiplex polymerase chain reactions each covering the three AZF regions, is still fully valid and appropriate for accurate diagnosis.
Somatostatin‐14 Actions on Dopamine‐ and Pituitary Adenylate Cyclase‐Activating Polypeptide‐Evoked Ca2+ Signals and Growth Hormone Secretion
Authors: Yunker W. K. , Chang J. P.
Published: July 2004

Using single‐cell Ca2+ imaging and a growth hormone (GH) radioimmunassay, we investigated somatostatin‐14 (SS14) inhibition of cAMP‐dependent, stimulated GH secretion from primary cultures of dispersed goldfish pituitary cells. The dopamine‐D1 receptor agonist SKF‐38393, and the hypothalamic neuropeptide pituitary adenylate cyclase‐activating polypeptide (PACAP) both elevated intracellular Ca2+ concentration ([Ca2+]i) and stimulated GH release. When increases in [Ca2+]i were prevented by intracellular loading of BAPTA, a Ca2+ chelator, SKF‐38393‐ and PACAP‐stimulated GH release were inhibited, suggesting that these Ca2+ signals are required for stimulated GH release. SS14 inhibited SKF‐38393‐ and PACAP‐stimulated GH release, but did not prevent these Ca2+ signals. Kinetic analysis revealed that SS14 lowered the maximum amplitude of the SKF‐38393‐ and PACAP‐evoked Ca2+ responses, but had no effect on other aspects of the Ca2+ signal. We then examined the ability of SS14 to act subsequent to dopamine‐D1 or PACAP receptor activation using the adenylate cyclase activator forskolin, or the membrane permeant cAMP analogue 8Br‐cAMP. Forskolin and 8Br‐cAMP both increased [Ca2+]i and GH secretion and, as expected, SS14 inhibited the resultant GH release. Although SS14 significantly increased the time to maximum amplitude of the forskolin‐evoked Ca2+ signals, it had no detectable effect on any of the kinetic parameters used to describe the Ca2+ signals evoked by 8Br‐cAMP. Taken together, these results establish that SS14 has the ability to suppress Ca2+‐dependent exocytosis by acting distal to elevations in [Ca2+]i. Furthermore, it appears likely that the cellular mechanisms underlying the observed effects of SS14 on Ca2+ signalling are upstream of cAMP and may be unrelated to those responsible for inhibiting GH release.
Glutamic Acid Decarboxylase 67 (GAD67) Gene Expression in Discrete Regions of the Rostral Preoptic Area Change During the Oestrous Cycle and with Age
Authors: Cashion A. B. , Smith M. J. , Wise P. M.
Published: July 2004

Gamma‐aminobutyric acid (GABA), an inhibitory neurotransmitter, is important to the timing and amplitude of the gonadotrophin‐releasing hormone (GnRH)‐induced luteinizing hormone (LH) surge on pro‐oestrus. Data suggest that GABA input in the preoptic area must decrease for a normal LH surge to occur in young rats. We have previously found that ageing alters the timing and amplitude of the LH surge. Therefore, this study focused on changes in GAD67 gene expression, a reflection of GABA synthesis, in two regions of the rostral preoptic area, the organum vasculosum of the lamina terminalis (OVLT) and the anteroventral periventricular nucleus (AVPV) during the oestrous cycle and with age. We assessed the possibility that the expression of GAD67 mRNA in these regions displays time‐related and age‐dependent changes on pro‐oestrus. Our results demonstrate that, with age, overall expression of GAD67 mRNA decreases in the area surrounding the OVLT and in the AVPV. Young rats display a diurnal rhythm in GAD67 mRNA in both regions. GAD67 mRNA expression is high during the early morning hours of pro‐oestrus and then declines around the time of the GnRH‐induced LH surge. In addition, the diurnal rhythm disappears in the AVPV and is attenuated in the area surrounding the OVLT of middle‐aged proestrous rats. These findings suggest that a loss of rhythmicity in GAD67 gene expression and maintenance of inhibitory tone on proestrous afternoon may alter the timing and amplitude of the LH surge, as previously observed in middle‐aged rats.
Strategic Delegation with Multiproduct Firms
Authors: Moner‐Colonques Rafael , Sempere‐Monerris José J. , Urbano Amparo
Published: July 2004

This paper shows that a multiproduct firm may find it optimal not to delegate the sales of all products and therefore to employ different distribution channels for different products. It faces the following trade‐off: There is a strategic effect associated with delegation, but if both products' sales are delegated, intrafirm competition is not internalized. By delegating the sales of just one of the products while selling the other product directly—partial delegation—the multiproduct manufacturer strikes just the right compromise: The externalities between its owns products are internalized partially while a strategic advantage is achieved against its rival single‐product manufacturer. Partial delegation also holds if both products are sold by a common retailer; it dominates full delegation when both manufacturers are multiproduct firms.
Patents, Secrets, and the First‐Inventor Defense
Authors: Denicolò Vincenzo , Alberto Franzoni Luigi
Published: July 2004

We analyze optimal patent design when innovators can rely on secrecy to protect their innovations. Secrecy has no fixed term but does not preclude accidental disclosure nor independent creation by other inventors. We derive the optimal scope of the rights conferred to such second inventors, showing that if the patent life is set optimally, second inventors should be allowed to patent and to exclude first inventors who have relied on secrecy. We then identify conditions under which it is socially desirable to increase patent life as much as is necessary to induce first inventors to patent. The circumstances in which it is preferable that they rely on secrecy seem rather limited.
Obstructive sleep apnoea and cardiovascular disease
Authors: Hamilton G. S. , Solin P. , Naughton M. T.
Published: July 2004

Abstract

Obstructive sleep apnoea (OSA) leads to both acute and chronic physiological effects on the cardiovascular system. There is now a large amount of evidence showing that OSA is independently associated with a wide spectrum of clinical cardiovascular disease (CVD). Evidence for a causative effect of OSA is strongest for hypertension, but is weaker for other cardiovascular disorders. Large prospective trials are ongoing and when results become available the link between OSA and CVD is likely to be strengthened. Treatment of OSA with continuous positive airway pressure has been shown to improve blood pressure, particularly in those with hypertension, and also left ventricular ejection fraction in those with congestive heart failure. Given the high prevalence of OSA in the community and its effects on the cardiovascular system, symptoms of this disorder should be sought in patients being investigated or treated for CVD. (Intern Med J 2004; 34: 420−426)
The gelation mechanism and application to commodities of non‐water gel comprising PEG
Authors: Kashiwai T. , Sugiyama T. , Toki I. , Nagashima S. , Goto H. , Iida N. , Yamagata Y.
Published: July 2004

We developed a non‐water gel product comprising HPC and PEG, reacting hydration with water. We investigated the gelation mechanism of HPC/PEG gel by means of a stress‐controlled rheometer and an X‐ray diffractometer. According to the results, the mechanism has two factors: entanglement of the HPC polymer chain and cross‐linkage of the microcrystal domain of the HPC main chain. The HPC/PEG gel is useful as the basic material of the cosmetic plaster that causes skin surface temperature to rise and the blood stream to accelerate.
The characteristics of a microcapsule with an entirely new wall material, ‘silicone–resin–polypeptide’, and its application
Authors: Ueda Y. , Segawa A. , Yoshioka M.
Published: July 2004

Many studies on the preparation and application of microcapsules have been reported in the literature. We developed an innovative encapsulation technology by using silicone–resin–polypeptide as the encapsulating material. The resultant microcapsule was easily prepared from silicone–resin–polypeptide. For this microcapsule not only was the extent of encapsulation as high as 90%, but the particle size could be controlled to obtain very small sizes (average particle diameter was 2.2 μm) as well. Moreover, these microcapsules were resistant to relatively high shear forces and were stable over a long‐time period. Application in cosmetics by using microcapsule involving UV absorbers was examined. It was possible to apply organic UV absorbers in water‐rich formulations without any surfactant. This formulation demonstrated a good moisturizing and soft skin feel. The result showed this microcapsule might be widely applied in cosmetics.
A novel polymer anti‐irritant barrier film for cosmetics
Authors: Kuroda A. , Iyanagi H.
Published: July 2004

Currently, we encounter many chemical substances that can affect the skin through contact in our daily life. To keep these irritants away from us, it is very effective to create a dermal barrier film that can prevent penetration of irritants into the skin. For the purpose, we evaluated the permeation characteristics of currently available film‐forming polymers, but almost all were found ineffective as barriers. Our investigation led us to fluoroalkylacrylate–polyglycolmethacrylate–alkylmethacrylate–copolymer (F–copolymer), a new acrylic copolymer. This polymer is soluble in water and can easily be incorporated into various cosmetic products. It consists of hydrophilic and lipophilic groups with fluorine units, and forms a durable, continuous film that is resistant to both water and oil upon drying. Testing on human subjects has demonstrated F‐copolymer's effectiveness in countering irritation caused by water‐soluble materials, including methyl paraben, lactic acid, and oil‐soluble materials, like butyl paraben and methyl saricylate.
Factors of Convergence and Divergence in Union Membership
Authors: Machin Stephen
Published: July 2004

This paper considers the extent to which union decline in Britain has been characterized by convergence or divergence in union membership rates for people with different personal and job characteristics. It compares individual union membership in 1975 and 2001 to identify some significant factors of convergence and divergence, which indicate temporal instability in the relationship between union membership and a number of its determinants. Identification of these factors of convergence and divergence should be useful to several parties, including industrial relations scholars and union organizers.
Workplace Risk, Establishment Size and Union Density
Authors: Fenn Paul , Ashby Simon
Published: July 2004

The health and safety risk faced by individual employees can be treated as an unobservable latent variable which manifests itself at workplace level through reported counts of work‐related injuries and illnesses over a given interval. This paper presents results from count data regressions using data from the 1998 Workplace Employee Relations Survey. The findings strongly support the view that employees in larger establishments have a lower probability of being injured or falling ill. In addition, establishments with a higher proportion of unionized employees, and with health and safety committees, were associated with higher numbers of reported injuries and illnesses.
Collective Bargaining and Within‐firm Wage Dispersion in Spain
Authors: Canal Domínguez Juan Francisco , Gutiérrez César Rodríguez
Published: July 2004

This paper analyses the effect of collective bargaining on within‐firm wage dispersion for the case of Spain. What is relevant in the Spanish case is to compare the effect of the two basic levels of bargaining (firm and sector) on wage dispersion. By using the Oaxaca–Blinder decomposition, this paper concludes that collective agreements at firm level have a negative effect on wage dispersion. At the same time, firms that have signed these types of agreements show greater wage dispersion than those covered by agreements at the sector level, owing to the positive and compensating effect of firms’ and workers’ features.
The Price is Right? Pay Settlements and Nominal Wage Rigidity in Britain
Authors: Brown Donna , Ingram Peter , Wadsworth Jonathan
Published: July 2004

We examine representative, group‐level wage settlement data to augment the debate on nominal pay rigidity in Britain. We investigate the characteristics of groups that settle at zero and the role of within‐firm and external influences. Nominal settlement cuts are rare. Zero nominal wage settlements are more common, but still relatively unusual, highest during (low‐inflation) recessionary periods. Small groups, above all firms under duress, appear most likely to settle at zero. Once a group settles at zero it is unlikely to do so again in the short run.
Innate immunity in aging: impact on macrophage function
Authors: Plowden Julie , Renshaw‐Hoelscher Mary , Engleman Carrie , Katz Jacqueline , Sambhara Suryaprakash
Published: July 2004

Innate and adaptive immune functions decline with age, leading to increased susceptibility to infectious diseases and cancer, and reduced responses to preventive vaccination in the elderly population. Macrophages function as ‘pathogen sensors’ and play an important role in the initiation of inflammatory responses, elimination of pathogens, manipulation of the adaptive immune response and reparation of damaged tissue. In this paper, we review the literature addressing the impact of aging on the macrophage population.
Genome‐scale expression profiling of Hutchinson–Gilford progeria syndrome reveals widespread transcriptional misregulation leading to mesodermal/mesenchymal defects and accelerated atherosclerosis
Authors: Csoka Antonei B. , English Sangeeta B. , Simkevich Carl P. , Ginzinger David G. , Butte Atul J. , Schatten Gerald P. , Rothman Frank G. , Sedivy John M.
Published: July 2004

Hutchinson–Gilford progeria syndrome (HGPS) is a rare genetic disease with widespread phenotypic features resembling premature aging. HGPS was recently shown to be caused by dominant mutations in the LMNA gene, resulting in the in‐frame deletion of 50 amino acids near the carboxyl terminus of the encoded lamin A protein. Children with this disease typically succumb to myocardial infarction or stroke caused by severe atherosclerosis at an average age of 13 years. To elucidate further the molecular pathogenesis of this disease, we compared the gene expression patterns of three HGPS fibroblast cell strains heterozygous for the LMNA mutation with three normal, age‐matched cell strains. We defined a set of 361 genes (1.1% of the approximately 33 000 genes analysed) that showed at least a 2‐fold, statistically significant change. The most prominent categories encode transcription factors and extracellular matrix proteins, many of which are known to function in the tissues severely affected in HGPS. The most affected gene, MEOX2/GAX, is a homeobox transcription factor implicated as a negative regulator of mesodermal tissue proliferation. Thus, at the gene expression level, HGPS shows the hallmarks of a developmental disorder affecting mesodermal and mesenchymal cell lineages. The identification of a large number of genes implicated in atherosclerosis is especially valuable, because it provides clues to pathological processes that can now be investigated in HGPS patients or animal models.
Immunity and aging: the enemy within?
Authors: DeVeale Brian , Brummel Ted , Seroude Laurent
Published: July 2004

Functional analyses of changes in the immune response indicate that aging is associated with a decline of adaptive immunity whereas innate immunity is ramped up. Gene expression studies also support age‐dependent changes in immunity. Studies using a large panel of methodologies and multiple species show that some of the most dramatic transcriptional changes that occur during aging are associated with immunity. This observation leads to two fundamental questions: (1) Why is the immune response altered with age? (2) Is this a consequence of aging or does it contribute to it? The origin of these changes and the mechanistic relationship among them as well as with aging must be identified. In mammals, this task is complicated by the interdependence of the innate and adaptive immune systems. The value of invertebrates as model organisms to help answer these questions is presented. This includes a description of the immune response in invertebrate models and how it compares with vertebrates, focusing on conserved pathways. Finally, these questions are explored in light of recent reports and data from our laboratory. Experimental alterations of longevity indicate that the differential expression of immunity‐related genes during aging is linked to the rate of aging. Long‐lived nematodes are more resistant to pathogens and blocking the expression of immune‐related genes can prevent lifespan extension. These observations suggest that the immune response has a positive effect on longevity, possibly by increasing fitness. By contrast, it has been reported that activation of the immune system can reduce longevity upon starvation. We also observed that deregulation of the immune response has drastic effects on viability and longevity in Drosophila. These data suggest that the immune response results in a trade‐off between beneficial and detrimental effects that might profoundly affect the aging process. Given this, immunity may be an ally early in life, but turns out to be an enemy as we age.
Regulation of aging and innate immunity in C. elegans
Authors: Kurz C. Leopold , Tan Man‐Wah
Published: July 2004

The free‐living soil nematode Caenorhabditis elegans is a versatile model for the study of the genetic regulation of aging and of host–pathogen interactions. Many genes affecting multiple processes, such as neuroendocrine signalling, nutritional sensing and mitochondrial functions, have been shown to play important roles in determining the lifespan of C. elegans. The DAF‐2‐mediated insulin signalling pathway is the major pathway that regulates aging in this nematode and this role appears universal; neuroendrocrine signalling also affects aging in Drosophila and mice. Recent studies have shown that the innate immune function in C. elegans is modulated by signalling from the TGF‐beta‐like, the p38 MAPK and the DAF‐2 insulin pathways. The requirement for the DAF‐2 pathway in modulating aging and immunity suggests that these processes may be linked at the molecular level. It is well known that as humans age, immunosenescence occurs in which there is a general degradation of immune efficiency. However, the molecular mechanisms involved in this process remain unclear. In this review, we discuss the molecular mechanisms that modulate aging and immune response and attempt to suggest molecular links between these two processes.
Software metrics
Authors: Cook Michael L.
Published: July 2004

Software metrics, an area of software engineering, is concerned with various measurements of computer software and its development. Software metrics, its importance, some current areas of investigation, and problems are described. An annotated bibliography of work in software metrics is included.I often say that when you can measure what you are speaking about, and express it in numbers, you know something about it; but when you cannot measure it, when you cannot express it in numbers, your knowledge is of a meagre and unsatisfactory kind: it may be the beginning of knowledge, but you have scarcely, in you thoughts, advanced to the stage of
science
, whatever the matter may be.---Lord Kelvin,
Popular Lectures and Addresses
, volume 1, 1889
Reflections on capital-intensive software technology
Authors: Wegner Peter
Published: July 2004

"Capital" is defined as a reusable resource, and it is shown that many software engineering activities are capital-intensive in the sense that they serve to create reusable resources. Just as the Eskimo has many different words for snow, we have many words for reusability, including commonality, portability, modularity, abstraction, generality, equivalence, maintainability, adaptability, and sharability. A plausible conclusion is that reusability of the resources we create is as important in our lives as snow is in the life of the Eskimo. The definition of capital in terms of reusability suggests that the reason for the importance of reusability is in part economic. But the drive to create permanent rather than transitory artifacts has aesthetic and intellectual as well as economic motivations, and is part of man's desire for immortality.
The impact of rapid prototyping on specifying user requirements
Authors: Gomaa Hassan
Published: July 2004

Prototyping has been recognized as being a powerful and indeed essential tool in many branches of engineering. Although software prototyping is often considered too expensive, correcting ambiguities and misunderstandings at the requirements specification stage is significantly cheaper than correcting a system after it has gone into production. This paper describes how rapid prototyping impacts the Requirements Analysis and Specification phase of the software life cycle. This is illustrated by describing the experience gained from a prototype used to assist in the requirements specification of a system to manage and control an integrated circuit fabrication facility. The cost of the prototype was less than 10 percent of the total software development cost.
Principles for software environments
Authors: Magel Kenneth
Published: July 2004

A large number of software development support environments have been developed during the last few years. Many more are being developed now. This paper presents some principles which should be followed in the development and evolution of such an environment. Stress is placed on the idea that an environment evolves and that the ultimate success or failure of the environment depends on its evolution more than on its initial appearance.
Debugging methodology
Authors: Gramlich Wayne C.
Published: July 2004

Two sessions were held on the general topic of debugging methodology. Both were moderated by R. Stockton Gaines. During the first session five speakers presented short talks on their workshop submissions. Each talk was followed by a brief question and answer period. The format of the second session was that of an open discussion. The talks presented in the first session have been briefly summarized. The remaining notes of these two sessions have been arranged topically rather than chronologically.
Debugging "level"
Authors: Hamlet Dick
Published: July 2004

Debugging techniques originated with low-level programming languages, where the memory dump and interactive word-by-word examination of memory were the primary tools. "High-level" debugging is often no more than low-level techniques adapted to high-level languages. For example, to examine the execution of an operational specification one state at a time by setting breakpoints, is superior to doing the same thing to a machine-language program, but only because the language level has improved; the debugging remains primitive. This paper attempts a radical definition of debugging level, and illustrates it with a technique for ordering the execution of concurrent processes in a way that follows their design structure.

Division of a program into a collection of cooperating processes is a means of controlling the complexity of each process. However, in execution the program--development structure is ignored, with the result that the advantages of decomposition are lost. What the designer has divided and conquered, the debugger sees as an overwhelming monolith. The technique proposed here causes the focus of execution to follow the design structure, in a way that does not require detailed user direction.
Knowledge-based debugging
Authors: Linton Mark A. , Balzer Robert , Cunningham R. J. , Green Cordell , Sedlmeyer Robert , Solloway Elliott , Swartout William , Zave Pamela
Published: July 2004

Robert Balzer
began the session by presenting an overview of where debugging fits into knowledge-based programming systems. He distinguished between differences in paradigm (the traditional software engineering approach in which the source code is the first formal representation vs. the operational specification approach in which the specification is both formal and executable and from which the implementation is formally derived) and differences in technology (traditional debuggers vs. knowledge-based tools), pointing out that it is possible to use traditional debugging techniques with the operational specification paradigm as well as use knowledge-based tools with the traditional software engineering paradigm.

Balzer presented the operational specification paradigm for software development. The basic idea is that an implementation is derived from a specification through transformations chosen by the programmer and applied by the system. Assuming each transformation is correct, the resulting implementation will accurately reflect the intentions of the specification.
Knowledge-based fault localization in debugging
Authors: Sedlmeyer Robert L. , Thompson William B. , Johnson Paul E.
Published: July 2004

Fault localization in program debugging is the process of identifying program statements which cause anomalous behaviour. We have developed a prototype, knowledge-based model of the fault localization process. Novel features of the model include multiple localization tactics and a recognition-based mechanism for program abstraction. An explicit division of knowledge from the applications, programming and language domains facilitate model tuning within as well as across applications domains. We describe model structure and performance for a class of faults associated with master file update programs. We foresee applications of the model as an initial cognitive theory of expertise in fault localization and as a partially automated debugging tool.
The application of error-sensitive testing strategies to debugging
Authors: Clarke Lori A. , Richardson Debra J.
Published: July 2004

Program errors can be considered from two perspectives -- cause and effect. The goal of program testing is to detect errors by discovering their effects, while the goal of debugging is to search for the associated cause. In this paper, we explore ways in which some of the results of testing research can be applied to the debugging process. In particular, computation testing and domain testing, which are two error-sensitive test data selection strategies, are described. Ways in which these selection strategies can be used as debugging aids are then discussed.
Integrated environments
Authors: Lee Insup
Published: July 2004

The session on debugging in integrated environments started with Fairley's characterization of integrated environments as follows: (1) versatile collection of analysis, design, implementation, testing, and maintenance tools; (2) consistent user interface among the tools; (3) common representation of information (e.g., Stoneman's database model, Unix pipe); (4) history/version control/configuration management capability; and (5) encouragement of good practice. He then asked the audience the following questions: (1) what is your view of environments? (2) what possibilities exist for debugging in integrated environments that do not exist in a mere collection of tools? (3) what is the difference between high--level debugging and low--level debugging with high--level tools?
An approach to high-level debugging of distributed systems
Authors: Bates Peter , Wileden Jack C.
Published: July 2004

As part of a study of methods and strategies for problem solving in a distributed environment [Less80], we have been investigating techniques suitable for use in debugging programs written for implementation on distributed processing networks.

Traditional debugging methods emphasize techniques that apply at the level of computation units and generally allow users to examine, and possibly alter, the state of a computation. Interactive debugging monitors are probably the most powerful implementations of the traditional method and usually permit a user to examine an entire snspshot of system state at any step of the computation. It is the job of the debugger (usually a person directing the error search) to determine what units are relevant to some problem, examine the units in whatever fashion is available, and then fit the results of these examinations into a model of how the computation works. Two elements essential to the successful completion of the debugging task are evident here: the ability to monitor, in some meaningful way, the relevant system activity so as to understand how system behavior differs from the debugger's model, and the ability to perform experiments based (implicitly or explicitly) on the information gathered. Through the interaction of these two elements a debugger attempts to gain an understanding of the causes of an error or at least to note where the implementation and the expected behavior differ.
Implementation issues II
Authors: Kenniston Michael S. , Atkinson Russ
Published: July 2004

The panelists were asked to address three questions. The three sections below are summaries of the ideas discussed in response to each of these questions.

1. When debugging a program, what information about that program is important for presentation to the user? What techniques can the debugger use to determine such information?

While helping to develop a debugger, John Johnson had observed many programmers using it, and had noticed two distinct styles of information gathering:

• Many programmers began by getting fairly small amounts of information. They simply wanted an overview of the "flow" of the program, in order to get a general understanding of its behavior.

• After suspicion had been narrowed down to- a particular area within the program, the users wanted as much information as possible, formatted nicely.
SIMOB
Authors: Barra Knut , Dahle Hans Petter
Published: July 2004

To reason correctly over what is happening during an execution is often hard just by looking at the program text. To assist programmers and others to understand what really is going on, a portable tool for observation of SIMULA executions has been designed at the Norwegian Computing Center. In this article the S-PORT project and the main features of the tool are described.
High level language debugging with a compiler
Authors: Ferrante Jeanne
Published: July 2004

In this paper, we start from the basic premise of wanting an interactive high level language debugger, and we explore the possibilities of achieving this using a compiler. We outline the functional capabilities desired, and suggest means of achieving them using a compiler. Most of these entail requirements on the compiler, and our suggestions may be viewed as justification for modularizing compiler design.
Hardware assisted high level debugging
Authors: Gentleman W. Morven , Hoeksma Henry
Published: July 2004

Hardware assistance has long been used for logic level and functional unit level hardware debugging, as well as for machine language level software debugging. Such hardware assistance includes probes to detect signals, comparators to identify matches with expected patterns, buffers to record selected events, and independent logic and software to analyze and interpret the observed events. It can also include the ability to generate selected signals to stimulate the object being debugged and the ability to isolate it from normal changes so its state can be examined.

Through knowledge of the data structures and algorithms used by the operating systems, and the runtime representation, register usage, and code bursts produced by compilers, it is possible to take advantage of such hardware assistance in high-level debugging. High level debugging here refers to debugging in terms of abstractions supported by the operating system and programming languages, as well as user defined abstractions built on top of these.