bluuebunny/crossref_metadata_2025 huggingface dataset:
Induction of an acetaminophen-sensitive cyclooxygenase with reduced sensitivity to nonsteroid antiinflammatory drugs
Authors: Simmons Daniel L. , Botting Regina M. , Robertson Philip M. , Madsen Matthew L. , Vane John R.
Published: July 2002

The transformed monocyte/macrophage cell line J774.2 undergoes apoptosis when treated for 48 h with competitive inhibitors of cyclooxygenase (COX) isoenzymes 1 and 2. Many of these nonsteroid antiinflammatory drugs (NSAIDs), but in particular diclofenac, induce during this time period a COX activity that coincides with a robust induction of COX-2 protein. Induction of this activity requires high, apoptosis-inducing concentrations of diclofenac (>100 μM). Prolonged treatment of J774.2 cells with lower doses of diclofenac inhibits COX activity, indicating that diclofenac is a time-dependent, pseudoirreversible inhibitor of COX-2. It is difficult to wash out the inhibition. However, the activity evoked by high concentrations of diclofenac has a profoundly distinct COX active site that allows diclofenac, its inducer, to be washed readily from its active site. The diclofenac-induced activity also has the unusual property of being more sensitive to inhibition by acetaminophen (IC
50
= 0.1–1.0 mM) than COX-2 induced with bacterial lipopolysaccharide. Moreover, relative to COX-1 or COX-2, diclofenac-induced enzyme activity shows significantly reduced sensitivity to inhibition by diclofenac or other competitively acting nonsteroid antiinflammatory drugs (NSAIDs) and the enzyme activity is insensitive to aspirin. If the robust induction of COX-2 observed is responsible for diclofenac-induced COX enzyme activity, it is clear that COX-2 can, therefore, exist in two catalytically active states. A luciferase reporter–construct that contains part of the COX-2 structure and binds into the membrane showed that chronic diclofenac treatment of fibroblasts results in marked mobilization of the fusion protein. Such a mobilization could result in enzymatically distinct COX-2 populations in response to chronic diclofenac treatment.
Spin-lattice relaxation of laser-polarized xenon in human blood
Authors: Wolber Jan , Cherubini Andrea , Dzik-Jurasz Andrzej S. K. , Leach Martin O. , Bifone Angelo
Published: July 2002

The nuclear spin polarization of
129
Xe can be enhanced by several orders of magnitude by using optical pumping techniques. The increased sensitivity of xenon NMR has allowed imaging of lungs as well as other
in vivo
applications. The most critical parameter for efficient delivery of laser-polarized xenon to blood and tissues is the spin-lattice relaxation time (
T
1
) of xenon in blood. In this work, the relaxation of laser-polarized xenon in human blood is measured
in vitro
as a function of blood oxygenation. Interactions with dissolved oxygen and with deoxyhemoglobin are found to contribute to the spin-lattice relaxation time of
129
Xe in blood, the latter interaction having greater effect. Consequently, relaxation times of
129
Xe in deoxygenated blood are shorter than in oxygenated blood. In samples with oxygenation equivalent to arterial and venous blood, the
129
Xe
T
1
s at 37°C and a magnetic field of 1.5 T were 6.4 s ± 0.5 s and 4.0 s ± 0.4 s, respectively. The
129
Xe spin-lattice relaxation time in blood decreases at lower temperatures, but the ratio of
T
1
in oxygenated blood to that in deoxygenated blood is the same at 37°C and 25°C. A competing ligand has been used to show that xenon binding to albumin contributes to the
129
Xe spin-lattice relaxation in blood plasma. This technique is promising for the study of xenon interactions with macromolecules.
Sustained correction of bleeding disorder in hemophilia B mice by gene therapy
Authors: Wang Lili , Takabe Kazuaki , Bidlingmaier Scott M. , Ill Charles R. , Verma Inder M.
Published: July 2002

Mice generated by disrupting the clotting factor IX gene exhibit severe bleeding disorder and closely resemble the phenotype seen in hemophilia B patients. Here we demonstrate that a single intraportal injection of a recombinant adeno-associated virus (AAV) vector encoding canine factor IX cDNA under the control of a liver-specific enhancer/promoter leads to a long-term and complete correction of the bleeding disorder. High level expression of up to 15–20 μg/ml of canine factor IX was detected in the plasma of mice injected with 5.6 × 10
11
particles of an AAV vector for >5 months. The activated partial thromboplastin time of the treated mice was fully corrected to higher than normal levels. Liver-specific expression of canine factor IX was confirmed by immunofluorescence staining, and secreted factor IX protein was identified in the mouse plasma by Western blotting. All treated mice survived the tail clip test without difficulty. Thus, a single intraportal injection of a recombinant adeno-associated virus vector expressing factor IX successfully cured the bleeding disorder of hemophilia B mice, proving the feasibility of using AAV-based vectors for liver-targeted gene therapy of genetic diseases.
DRONC, an ecdysone-inducible
Drosophila
caspase
Authors: Dorstyn Loretta , Colussi Paul A. , Quinn Leonie M. , Richardson Helena , Kumar Sharad
Published: July 2002

Caspases play an essential role in the execution of programmed cell death in metazoans. Although 14 caspases are known in mammals, only a few have been described in other organisms. Here we describe the identification and characterization of a
Drosophila
caspase, DRONC, that contains an amino terminal caspase recruitment domain. Ectopic expression of DRONC in cultured cells resulted in apoptosis, which was inhibited by the caspase inhibitors p35 and MIHA. DRONC exhibited a substrate specificity similar to mammalian caspase-2. DRONC is ubiquitously expressed in
Drosophila
embryos during early stages of development. In late third instar larvae,
dronc
mRNA is dramatically up-regulated in salivary glands and midgut before histolysis of these tissues. Exposure of salivary glands and midgut isolated from second instar larvae to ecdysone resulted in a massive increase in
dronc
mRNA levels. These results suggest that DRONC is an effector of steroid-mediated apoptosis during insect metamorphosis.
Hyaluronan forms specific stable tertiary structures in aqueous solution: A
13
C NMR study
Authors: Scott John E. , Heatley Frank
Published: July 2002

13
C NMR spectra of aqueous solutions of hyaluronan (HA) of high molecular mass, before and after digestion with testicular hyaluronidase, and of hyaluronan methyl ester were obtained at 125.8 MHz. Carbonyl peaks were assigned by using selective decoupling techniques. Spectra of digested and undigested HA showed sharp signals, except for that assigned to the acetamido carbonyl carbon in the high polymer, which was much broadened. The decreased mobility of this C⩵O, thus demonstrated, was caused by restricted rotation. As part of the rigid CO—NH unit, rotation of NH was therefore similarly restricted, probably because of an intermolecular H bond from NH to carboxylate groups on neighbouring HA molecules. This bond was confirmed by comparing esterified HA with unmodified HA. Methyl esterification of carboxylates was accompanied by changes in acetamido C⩵O resonances consistent with increased mobility of CO—NH groups. Ester C⩵O resonances were sharp, proving that they did not participate in sterically restricted structures such as the proposed H bonds involving unesterified carboxylate groups. C⩵O resonances report on the environments and on the interrelationships of amide and carboxylate groups. A detailed structure suggested for high-molecular-mass HA in aqueous solution takes account of NMR and x-ray fiber diffraction data. Antiparallel HA chains overlap in meshworks stabilized by specific H bonds and hydrophobic bonds. This highly cooperative structure, formally equivalent to β-sheets seen in proteins, is not stable in low-molecular-mass HA solution. The results relate to structures proposed for shape modules in extracellular matrix involving chondroitin and keratan sulfates, which resemble HA in their stereochemistry.
Delayed-type hypersensitivity toPhlebotomus papatasisand fly bite: An adaptive response induced by the fly?
Authors: Belkaid Yasmine , Valenzuela Jesus G. , Kamhawi Shaden , Rowton Edgar , Sacks David L. , Ribeiro José M. C.
Published: July 2002

The saliva of bloodsucking arthropods contains a large array of pharmacologically active compounds that assist hematophagy. Arthropod saliva is also responsible for causing uncomfortable allergic responses in its vertebrate hosts. In this article, we investigate whether the sand flyPhlebotomus papatasi, known to produce a strong delayed-type hypersensitivity (DTH) in humans, could benefit from, and possibly adaptively induce, this response in their vertebrate hosts. In this study, we show that flies fed on humans to completion nearly twice as fast in DTH sites as compared with normal skin sites. DTH sites had significantly larger blood flow as measured by the laser Doppler method. Sand flies feeding at sites in mouse ears that had a DTH response also fed faster than at normal sites. We conclude that in the case ofP. papatasi,and possibly other arthropods such as fleas and bed bugs, the strong saliva-induced DTH response may reflect an adaptation of the fly to manipulate host immunity for the insect's own advantage.
Multiple sclerosis: Comparison of copolymer-1- reactive T cell lines from treated and untreated subjects reveals cytokine shift from T helper 1 to T helper 2 cells
Authors: Neuhaus Oliver , Farina Cinthia , Yassouridis Alexander , Wiendl Heinz , Then Bergh Florian , Dose Tatjana , Wekerle Hartmut , Hohlfeld Reinhard
Published: July 2002

Copolymer 1 (COP), a standardized mixture of synthetic polypeptides consisting ofl-glutamic acid,l-lysine,l-alanine, andl-tyrosine, has beneficial effects in multiple sclerosis and experimental autoimmune encephalomyelitis. We selected a panel of 721 COP-reactive T cell lines (TCL) from the blood of COP-treated and untreated multiple sclerosis patients and from healthy donors by using the split-well cloning technique. All TCL selected with COP proliferated in response to COP but not to myelin basic protein (MBP). Conversely, 31 control TCL selected with MBP proliferated in response to MBP but not to COP. We used intracellular double-immunofluorescence flow cytometry for quantitative analysis of cytokine production (IL-4, IFN-γ) by the TCL. The majority of the COP-reactive TCL from untreated multiple sclerosis patients and normal donors predominantly produced IFN-γ and, accordingly, were classified as T helper 1 cells (TH1). In contrast, the majority of the COP-reactive TCL from COP-treated patients predominantly (but not exclusively) produced IL-4—i.e., were TH2 (P< 0.05 as assessed by using a suitable preference intensity index). Longitudinal analyses revealed that the cytokine profile of COP-reactive TCL tends to shift from TH1 to TH2 during treatment. Interestingly, although there was no proliferative cross-reaction, about 10% of the COP-reactive TCL responded to MBP by secretion of small amounts of IL-4 or IFN-γ, depending on the cytokine profile of the TCL. These results are consistent with a protective effect of COP-reactive TH2 cells. It is hypothesized that these cells are activated by COP in the periphery, migrate into the central nervous system, and produce immunomodulatory cytokines after local recognition of MBP.
Fluorescence microscopy with diffraction resolution barrier broken by stimulated emission
Authors: Klar Thomas A. , Jakobs Stefan , Dyba Marcus , Egner Alexander , Hell Stefan W.
Published: July 2002

The diffraction barrier responsible for a finite focal spot size and limited resolution in far-field fluorescence microscopy has been fundamentally broken. This is accomplished by quenching excited organic molecules at the rim of the focal spot through stimulated emission. Along the optic axis, the spot size was reduced by up to 6 times beyond the diffraction barrier. The simultaneous 2-fold improvement in the radial direction rendered a nearly spherical fluorescence spot with a diameter of 90–110 nm. The spot volume of down to 0.67 attoliters is 18 times smaller than that of confocal microscopy, thus making our results also relevant to three-dimensional photochemistry and single molecule spectroscopy. Images of live cells reveal greater details.
Prenatal stress produces learning deficits associated with an inhibition of neurogenesis in the hippocampus
Authors: Lemaire V. , Koehl M. , Le Moal M. , Abrous D. N.
Published: July 2002

Early experiences such as prenatal stress significantly influence
the development of the brain and the organization of behavior. In
particular, prenatal stress impairs memory processes but the mechanism
for this effect is not known. Hippocampal granule neurons are generated
throughout life and are involved in hippocampal-dependent learning.
Here, we report that prenatal stress in rats induced lifespan reduction
of neurogenesis in the dentate gyrus and produced impairment in
hippocampal-related spatial tasks. Prenatal stress blocked the increase
of learning-induced neurogenesis. These data strengthen
pathophysiological hypotheses that propose an early neurodevelopmental
origin for psychopathological vulnerabilities in aging.
Quantitative trait loci on chromosomes 3 and 17 influence phenotypes of the metabolic syndrome
Authors: Kissebah Ahmed H. , Sonnenberg Gabriele E. , Myklebust Joel , Goldstein Michael , Broman Karl , James Roland G. , Marks Jacqueline A. , Krakower Glenn R. , Jacob Howard J. , Weber James , Martin Lisa , Blangero John , Comuzzie Anthony G.
Published: July 2002

Recent research has emphasized the importance of the metabolic
cluster, which includes glucose intolerance, dyslipidemia, and high
blood pressure, as a strong predictor of the obesity-related
morbidities and premature mortality. Fundamental to this association,
commonly referred to as the metabolic syndrome, is the close
interaction between abdominal fat patterning, total body adiposity, and
insulin resistance. As the initial step in identifying major genetic
loci influencing these phenotypes, we performed a genomewide scan by
using a 10-centiMorgan map in 2,209 individuals distributed over 507
nuclear Caucasian families. Pedigree-based analysis using a variance
components linkage model demonstrated a quantitative trait locus (QTL)
on chromosome 3 (3q27) strongly linked to six traits representing these
fundamental phenotypes [logarithm of odds (lod) scores ranged from 2.4
to 3.5]. This QTL exhibited possible epistatic interaction with a
second QTL on chromosome 17 (17p12) strongly linked to plasma leptin
levels (lod = 5.0). Situated at these epistatic QTLs are candidate
genes likely to influence two biologic precursor pathways of the
metabolic syndrome.
Entry and survival ofSalmonella typhimuriumin dendritic cells and presentation of recombinant antigens do not require macrophage-specific virulence factors
Authors: Niedergang Florence , Sirard Jean-Claude , Blanc Corinne Tallichet , Kraehenbuhl Jean-Pierre
Published: July 2002

Macrophages have long been regarded as the main target encountered bySalmonella typhimurium,a Gram-negative facultative intracellular pathogen that invades the intestinal mucosa.S. typhimurium, however, are first internalized by dendritic cells. To gain new insights into the interactions betweenSalmonellaand the dendritic cells, we compared the fate of wild-typeS. typhimuriumand the virulence-attenuated PhoP constitutive (PhoPc) strain. The PhoPcstrain is impaired for entry and survival in mammalian cells and is poorly processed by macrophages for antigen presentation on MHC class II molecules. Here, we show that bone marrow-derived dendritic cells can similarly process and present a foreign antigen expressed by the invasive wild-type and the attenuated PhoPcS. typhimurium. This property correlates with equivalent entry and survival efficiencies of both strains in dendritic cells. In addition,Salmonellastrains mutated inmgtCB,sseC, andorfLgenes required for macrophage survival showed no defect in survival in dendritic cells. Together, these results indicate that uptake ofSalmonellaby dendritic cells and subsequent antigen processing and presentation do not depend on virulence factors important in macrophages.
The kidney is an important site for
in vivo
phenylalanine-to-tyrosine conversion in adult humans: A metabolic role of the kidney
Authors: Møller Niels , Meek Shon , Bigelow Maureen , Andrews James , Nair K. S.
Published: July 2002

Synthesis of Tyr in the human body occurs by hydroxylation of the indispensable amino acid Phe. Until now, it was believed that in humans, this process was restricted to the liver, but we provide compelling evidence of production of Tyr from Phe in the kidney. To determine whether the human kidney produces Tyr, we measured Tyr balance, the Tyr appearance rate, and the Phe-to-Tyr conversion in 12 healthy human subjects by using [
15
N]Phe and [
2
H
4
]Tyr as tracers. Renal plasma flow was measured by using paraaminohippurate, and sampling from the femoral artery and renal veins was performed. The results were compared with those obtained in 12 control subjects undergoing hepatic vein catheterization and infusion of identical tracers. In all 12 subjects, there was a net uptake of Phe by the kidney (2.2 ± 1.2 μmol/min), whereas Tyr was released (5.3 ± 1.5 μmol/min). In contrast, there was a net uptake of both Phe (9.5 ± 1.2 μmol/min) and Tyr (14.3 ± 1.3 μmol/min) by the splanchnic bed. Phe conversion to Tyr occurred at a rate of 5.2 ± 1.2 μmol/min in kidney and 3.0 ± 0.7 μmol/min in the splanchnic bed. The kidney contributed a substantial amount of Tyr to the systemic circulation where the splanchnic bed was a net remover of Tyr. Our results demonstrate that the kidney is the major donor of Tyr to the systemic circulation by its conversion of Phe to Tyr. This observation may have important clinical implications for patients with both renal and hepatic disease, who may be at risk of Phe overloading and Tyr deficiency, and it should be considered when parenteral or enteral nutrients are administered rich in Phe and low in Tyr.
Human aspartic protease memapsin 2 cleaves the β-secretase site of β-amyloid precursor protein
Authors: Lin Xinli , Koelsch Gerald , Wu Shili , Downs Debbie , Dashti Azar , Tang Jordan
Published: July 2002

The cDNAs of two new human membrane-associated aspartic proteases, memapsin 1 and memapsin 2, have been cloned and sequenced. The deduced amino acid sequences show that each contains the typical
pre
,
pro
, and aspartic protease regions, but each also has a C-terminal extension of over 80 residues, which includes a single transmembrane domain and a C-terminal cytosolic domain. Memapsin 2 mRNA is abundant in human brain. The protease domain of memapsin 2 cDNA was expressed in
Escherichia coli
and was purified. Recombinant memapsin 2 specifically hydrolyzed peptides derived from the β-secretase site of both the wild-type and Swedish mutant β-amyloid precursor protein (APP) with over 60-fold increase of catalytic efficiency for the latter. Expression of APP and memapsin 2 in HeLa cells showed that memapsin 2 cleaved the β-secretase site of APP intracellularly. These and other results suggest that memapsin 2 fits all of the criteria of β-secretase, which catalyzes the rate-limiting step of the
in vivo
production of the β-amyloid (Aβ) peptide leading to the progression of Alzheimer's disease. Recombinant memapsin 2 also cleaved a peptide derived from the processing site of presenilin 1, albeit with poor kinetic efficiency. Alignment of cleavage site sequences of peptides indicates that the specificity of memapsin 2 resides mainly at the S
1
′ subsite, which prefers small side chains such as Ala, Ser, and Asp.
Climate change is affecting altitudinal migrants and hibernating species
Authors: Inouye David W. , Barr Billy , Armitage Kenneth B. , Inouye Brian D.
Published: July 2002

Calendar date of the beginning of the growing season at high altitude in the Colorado Rocky Mountains is variable but has not changed significantly over the past 25 years. This result differs from growing evidence from low altitudes that climate change is resulting in a longer growing season, earlier migrations, and earlier reproduction in a variety of taxa. At our study site, the beginning of the growing season is controlled by melting of the previous winter's snowpack. Despite a trend for warmer spring temperatures the average date of snowmelt has not changed, perhaps because of the trend for increased winter precipitation. This disjunction between phenology at low and high altitudes may create problems for species, such as many birds, that migrate over altitudinal gradients. We present data indicating that this already may be true for American robins, which are arriving 14 days earlier than they did in 1981; the interval between arrival date and the first date of bare ground has grown by 18 days. We also report evidence for an effect of climate change on hibernation behavior; yellow-bellied marmots are emerging 38 days earlier than 23 years ago, apparently in response to warmer spring air temperatures. Migrants and hibernators may experience problems as a consequence of these changes in phenology, which may be exacerbated if climate models are correct in their predictions of increased winter snowfall in our study area. The trends we report for earlier formation of permanent snowpack and for a longer period of snow cover also have implications for hibernating species.
PMD fundamentals: Polarization mode dispersion in optical fibers
Authors: Gordon J. P. , Kogelnik H.
Published: July 2002

This paper reviews the fundamental concepts and basic theory of
polarization mode dispersion (PMD) in optical fibers. It introduces a
unified notation and methodology to link the various views and concepts
in Jones space and Stokes space. The discussion includes the relation
between Jones vectors and Stokes vectors, rotation matrices, the
definition and representation of PMD vectors, the laws of infinitesimal
rotation, and the rules for PMD vector concatenation.
Functional interaction between the Werner Syndrome protein and DNA polymerase δ
Authors: Kamath-Loeb A. S. , Johansson E. , Burgers P. M. J. , Loeb L. A.
Published: July 2002

Werner Syndrome (WS) is an inherited disease characterized by premature onset of aging, increased cancer incidence, and genomic instability. The WS gene encodes a 1,432-amino acid polypeptide (WRN) with a central domain homologous to the RecQ family of DNA helicases. Purified WRN unwinds DNA with 3′→5′ polarity, and also possesses 3′→5′ exonuclease activity. Elucidation of the physiologic function(s) of WRN may be aided by the identification of WRN-interacting proteins. We show here that WRN functionally interacts with DNA polymerase δ (pol δ), a eukaryotic polymerase required for DNA replication and DNA repair. WRN increases the rate of nucleotide incorporation by pol δ in the absence of proliferating cell nuclear antigen (PCNA) but does not stimulate the activity of eukaryotic DNA polymerases α or ɛ, or a variety of other DNA polymerases. Moreover, we show that functional interaction with WRN is mediated through the third subunit of pol δ: i.e., Pol32p of
Saccharomyces cerevisae
, corresponding to the recently identified p66 subunit of human pol δ. Absence of the third subunit abrogates stimulation by WRN, and stimulation is restored by reconstituting the three-subunit enzyme. Our findings suggest that WRN may facilitate pol δ-mediated DNA replication and/or DNA repair and that disruption of WRN-pol δ interaction in WS cells may contribute to the previously observed S-phase defects and/or the unusual sensitivity to a limited number of DNA damaging agents.
l
-Amino acid sensing by the extracellular Ca
2+
-sensing receptor
Authors: Conigrave Arthur D. , Quinn Stephen J. , Brown Edward M.
Published: July 2002

The extracellular calcium (Ca
2+
o
)-sensing receptor (CaR) recognizes and responds to (i.e., “senses”) Ca
2+
o
as its principal physiological ligand. In the present studies, we document that the CaR is activated not only by extracellular calcium ions but also by amino acids, establishing its capacity to sense nutrients of two totally different classes.
l
-Amino acids, especially aromatic amino acids, including
l
-phenylalanine and
l
-tryptophan, stereoselectively mobilized Ca
2+
ions in the presence of the CaR agonists, Ca
2+
o
, gadolinium (Gd
3+
o
), and spermine in fura-2-loaded human embryonic kidney (HEK-293) cells stably transfected with the human CaR.
l
-amino acid-dependent effects were observed above, but not below, a threshold level of Ca
2+
o
of approximately 1.0 mM.
l
-Amino acids, particularly aromatic amino acids, also stereoselectively enhanced the sensitivity of the CaR to its agonists, Ca
2+
o
and spermine. Branched-chain amino acids were almost inactive, and charged amino acids, including arginine and lysine, were much less effective than aromatic and other amino acids.
l
-amino acid mixtures emulating the amino acid composition of fasting human plasma reproduced the effects of high concentrations of individual
l
-amino acids on Ca
2+
mobilization and enhanced the sensitivity of the CaR to Ca
2+
o
. The data presented herein identify the CaR as a molecular target for aromatic and other
l
-amino acids. Thus, the CaR can integrate signals arising from distinct classes of nutrients: mineral ions and amino acids. The actions of
l
-amino acids on the CaR may provide explanations for several long recognized but poorly understood actions of dietary protein on calcium metabolism.
Dynamic imaging of coherent sources: Studying neural interactions in the human brain
Authors: Gross J. , Kujala J. , Hämäläinen M. , Timmermann L. , Schnitzler A. , Salmelin R.
Published: July 2002

Functional connectivity between cortical areas may appear as
correlated time behavior of neural activity. It has been suggested that
merging of separate features into a single percept (“binding”) is
associated with coherent gamma band activity across the cortical areas
involved. Therefore, it would be of utmost interest to image
cortico-cortical coherence in the working human brain. The frequency
specificity and transient nature of these interactions requires
time-sensitive tools such as magneto- or electroencephalography
(MEG/EEG). Coherence between signals of sensors covering different
scalp areas is commonly taken as a measure of functional coupling.
However, this approach provides vague information on the actual
cortical areas involved, owing to the complex relation between the
active brain areas and the sensor recordings. We propose a solution to
the crucial issue of proceeding beyond the MEG sensor level to estimate
coherences between cortical areas. Dynamic imaging of coherent sources
(DICS) uses a spatial filter to localize coherent brain regions and
provides the time courses of their activity. Reference points for the
computation of neural coupling may be based on brain areas of maximum
power or other physiologically meaningful information, or they may be
estimated starting from sensor coherences. The performance of DICS is
evaluated with simulated data and illustrated with recordings of
spontaneous activity in a healthy subject and a parkinsonian patient.
Methods for estimating functional connectivities between brain areas
will facilitate characterization of cortical networks involved in
sensory, motor, or cognitive tasks and will allow investigation of
pathological connectivities in neurological disorders.
Hyperactivity and impaired response habituation in hyperdopaminergic mice
Authors: Zhuang Xiaoxi , Oosting Ronald S. , Jones Sara R. , Gainetdinov Raul R. , Miller Gary W. , Caron Marc G. , Hen René
Published: July 2002

Abnormal dopaminergic transmission is implicated in
schizophrenia, attention deficit hyperactivity disorder, and drug
addiction. In an attempt to model aspects of these disorders, we have
generated hyperdopaminergic mutant mice by reducing expression of the
dopamine transporter (DAT) to 10% of wild-type levels (DAT knockdown).
Fast-scan cyclic voltammetry and
in vivo
microdialysis
revealed that released dopamine was cleared at a slow rate in knockdown
mice, which resulted in a higher extracellular dopamine concentration.
Unlike the DAT knockout mice, the DAT knockdown mice do not display a
growth retardation phenotype. They have normal home cage activity but
display hyperactivity and impaired response habituation in novel
environments. In addition, we show that both the indirect dopamine
receptor agonist amphetamine and the direct agonists apomorphine and
quinpirole inhibit locomotor activity in the DAT knockdown mice,
leading to the hypothesis that a shift in the balance between dopamine
auto and heteroreceptor function may contribute to the therapeutic
effect of psychostimulants in attention deficit hyperactivity disorder.
Neuroimaging of cerebral activations and deactivations associated with hypercapnia and hunger for air
Authors: Brannan Stephen , Liotti Mario , Egan Gary , Shade Robert , Madden Lisa , Robillard Rachel , Abplanalp Bart , Stofer Katie , Denton Derek , Fox Peter T.
Published: July 2002

There are defined medullary, mesencephalic, hypothalamic, and thalamic functions in regulation of respiration, but knowledge of cortical control and the elements subserving the consciousness of breathlessness and air hunger is limited. In nine young adults, air hunger was produced acutely by CO2inhalation. Comparisons were made with inhalation of a N2/O2gas mixture with the same apparatus, and also with paced breathing, and with eyes closed rest. A network of activations in pons, midbrain (mesencephalic tegmentum, parabrachial nucleus, and periaqueductal gray), hypothalamus, limbic and paralimbic areas (amygdala and periamygdalar region) cingulate, parahippocampal and fusiform gyrus, and anterior insula were seen along with caudate nuclei and pulvinar activations. Strong deactivations were seen in dorsal cingulate, posterior cingulate, and prefrontal cortex. The striking response of limbic and paralimbic regions points to these structures having a singular role in the affective sequelae entrained by disturbance of basic respiratory control whereby a process of which we are normally unaware becomes a salient element of consciousness. These activations and deactivations include phylogenetically ancient areas of allocortex and transitional cortex that together with the amygdalar/periamygdalar region may subserve functions of emotional representation and regulation of breathing.
Science against modernism: the relevance of the social theory of Michael Polanyi
Authors: Thorpe Charles
Published: July 2002

Science, as an institution, is widely taken by sociologists to exemplify the modern tendency towards vesting trust and authority in impersonal offices and procedures, rather than in embodied human individuals. Such views of science face an important challenge in the social philosophy of Michael Polanyi. His work provides important insights into the continuing role of embodied personal authority and tradition in science and, hence, in late modernity. I explicate Polanyi's relevance for social theory, through a comparison with Weber's essay ‘Science as a Vocation’. An understanding of the personal dimensions of trust and authority in science suggests practical limits to the position of Giddens on the disembedding of social relations and on the scepticism and reflexivity of modernity.
Class structure in a deeply divided society: class and ethnic inequality in Israel, 1974–1991
Authors: Yaish Meir
Published: July 2002

Despite the fact that in many societies ethnicity plays an important role in stratification processes, a common view held by students of stratification argues that the role of ascriptive criteria in stratification processes is diminishing, and that the main axis of the modern stratification system is rooted in the division of labour in the marketplace. Despite this, most Israeli sociologists have taken the ethnic and national cleavages to be the main axes of stratification in Israel.

This paper utilizes the 1974 and 1991 mobility surveys in Israel to examine changes over time in the association between ethnicity/nationality (i.e., Ashkenazi‐Jews, Sephardi‐Jews and Israeli‐Arabs) and class position in the Israeli stratification structure. It also examines the extent to which inequality of opportunity within the Israeliclassstructure is affected byethnicity/nationality.

Here it is found that the ethnic/national cleavage in Israel appears to have played a less important role over time in the allocation of Israeli men to class positions. It is shown that class crystallization processes that result from the differentiation of employment contracts in the marketplace produce a relatively common level of inequality of opportunity in Israel, across sub‐populations and over time. Any difference in the level of inequality of opportunity between the various sub‐populations would appear to result, in part, from different historical process of, and government policy towards, the three sub‐populations.
Déficits visuo‐spatiaux associés à la Maladie de Parkinson
Authors: Doyon Julien , Bourgeois Carole , Bédard Paul
Published: July 2002

La présente étude vise à préciser la nature des déficits visuo‐spatiaux observés dans la Maladie de Parkinson (MP) afin de mieux comprendre la pathophysiologie associée à cette maladie. Jusqu'à présent, l'investigation des troubles spatiaux chez ce groupe de patients a donné lieu à des résultats controversés, et ce possiblement en raison de l'intrusion de biais due à la présence de composantes motrices ou à l'implication d'habiletés relevant de l'intégrité des lobes frontaux dans les tâches expérimentales. Dans le but de départager l'influence de ces variables, et de définir davantage le(s) type(s) de demande(s) des processus cognitifs aptes à produire un déficit chez cette population clinique, 15 patients atteints de MP idiopathique, sans démence associée, et 15 sujets témoins sont évalués à l'aide de trois tâches visuo‐spatiales. Deux de ces épreuves font appels à des habiletés visuo‐spatiales de base et ne nécessitent pas de contribution motrice, soient la discrimination d'orientation de lignes et l'exécution d'opération mentale de rotation impliquant des stimuli tri‐dimensionnels. La troisième tâche consiste en une série de problèmes visuo‐spatiaux qui fait appel aux capacités de raisonnement visuo‐spatial et à la flexibilité intellectuelle, et qui s'est avérée sensible aux lésions corticales frontales. Les résultats montrent que les sujets MP ont un déficit à l'ensemble des trois tâches, suggérant ainsi la présence de troubles purement visuo‐spatiaux dans la Maladie de Parkinson. Les changements pathophysiologiques pouvant expliquer de tels déficits sont discutés.
Intuitive Perceptions of Decision‐making Strategy: Naive Assessors' Concepts of Integrative Complexity
Authors: Suedfeld Peter , de Vries Brian , Bluck Susan , Wallbaum Alistair B. C. , Schmidt Paul W.
Published: July 2002

Although there are measurable differences in integrative complexity among solutions that individuals generate in dealing with problems, it is uncertain to what extent people comprehend, recognize, and have preferences among different levels of complexity. Integrative complexity is a function of differentiation (the perception of several attributes within, or perspectives about, a topic) and integration (combining the differentiated characteristics in an interactive or synthesizing solution). The current paper reports two experiments dealing with how university students perceive, interpret, and choose among solutions differing in complexity. Experiment 1 showed that subjects accurately rated the complexity of described solutions differing along the continuum, but that their assessment of their own responses differed from the results of expert scoring. Their self‐estimated complexity was highly correlated with their preferences, and preferred complexity was reliably higher than either expert‐ or self‐assessed complexity of subject‐generated solutions. Subjects were able to hypothesize quite accurately about environmental and endogenous factors likely to affect complexity. Experiment 2 found that in response to problem scenarios, solutions selected as being potentially most effective were consistently more complex than solutions that participants considered themselves most likely to use. The idea of complexity seems to be intuitively recognizable and understandable by untrained subjects: They can and do distinguish among problem solutions (self‐generated or presented) that vary on that dimension, and are able to assess accurately the effects of relevant variables. Such subjects also share the bias shown by experts in favour of the superiority of more complex approaches.
Effects of Scope of Justice, Informant Ethnicity, and Information Frame on Attitudes towards Ethnicity‐based Selection
Authors: Singer Ming S.
Published: July 2002

The study ascertained whether attitudes towards ethnicity‐based employment selection would be affected by three variables: scope of justice, information frame, and informant ethnicity. Using a scenario approach, results showed that (1) European New Zealanders with greater scope of justice regarding Maori people were less opposed to an employment practice that involves granting preferential treatment to Maori candidates. (2) The frame of information about ethnicity‐based selection (i.e. preferential selection vs. diversity‐based selection) and informant ethnicity interacted with scope of justice in exerting a significant influence on respondents' views on ethnicity‐based selection. Furthermore, individuals' reactions to moral philosophers' justifications for merit or ethnicity‐based selection determined their overall attitudes towards each selection practice.
The Development of Memory for Serial Order: A Temporal‐contextual Distinctiveness Model
Authors: Brown Gordon D.A. , Vousden Janet I. , McCormack Teresa , Hulme Charles
Published: July 2002

A model of adult human memory, OSCAR, is applied to the development of memory for serial order. In the model, development of serial order memory is assumed to result from age‐related changes in a dynamic learning‐context signal that underpins memory for serial order. Developmental improvement in this dynamic learning‐context signal leads to more temporally distinctive representations in memory, and this leads in turn to a reduction in order errors. It is shown that the model correctly predicts developmental changes in the movement error gradients in children's serially ordered recall, as well as developmental changes in the number of movement errors obtained. The model is also applied to repetition errors across development.
A Measurement of Spatial Disparity: The Case of Income Inequality
Authors: Chakravorty Sanjoy
Published: July 2002

Traditionally, inequality measurements have been designed only for non-spatial applications, despite the argument that inequality is manifested in social space (and may be perceived spatially). Presented here is an approach to understanding urban inequality in terms of the spatial distribution of population and income. This is done with a general definition of spatial disparity (implying significant differences between neighbouring parcels); spatial disparity exists between contiguous parcels even when similar values are spatially clustered (as in the case of income). A family of spatial disparity measures is proposed: the basic measure of 'neighbourhood disparity' uses information on contiguity to arrive at individual disparity values for individual parcels, and an indexed value for an area. The process of neighbour identification is made simpler by using topologically structured spatial databases used in vector-based GIS. This methodology is used on 1990 census data to analyse disparities in the spatial distribution of income in Philadelphia to illustrate and compare the use, the basic measure and its weighted versions, and to identify and map general patterns of urban spatial income disparity. It is found that spatial income disparity is manifested in rings around the CBD, and that the distribution of black incomes is very heterogeneous (although the generalisability of both conclusions may be questioned).
Integration of an Activity-based Model System and a Residential Location Model
Authors: Ben-Akiva Moshe , Bowman John L.
Published: July 2002

We present an integrated discrete choice model system of a household's residential location choice and its members' activity and travel schedules. A daily schedule consists of tours, characterised by destinations, times of day and travel modes. The activity and travel models supply the residential model with an accessibility measure for each household member, namely the expected maximum utility among available daily activity schedules, conditioned by the chosen pattern of tours and, for workers, the workplace. A nested logit model system is estimated and applied for Boston. It does not fit the data quite as well as a work-trip-based comparison model, but its predictions capture additional effects attributable to the more comprehensive accessibility measure.
Firms, Governments and Innovation in the Chukyo Region of Japan
Authors: Edgington David W.
Published: July 2002

The study of innovation mechanisms in one of Japan's major industrial regions (Chukyo, based around Nagoya) is explored using a four-part model. This identifies the role of core assembly firms and their sub-contractors, national and local government agencies, local chambers of commerce and private-sector lobby groups. The Chukyo region innovation system (CRIS) was found to exhibit long-term stability and appears to have weathered the economic challenges of the late 1980s and early 1990s. The Chukyo region's emphasis on continuous upgrading and kaizen has given it particular competitive advantages in 'downstream' innovation activities; however, it now faces the challenge of moving further `upstream' into areas of basic research.
Ecological Constraints for Intergenerational Transmission of Attachment
Authors: Sagi Abraham , van IJzendoorn Marinus H. , Scharf Miri , Joels Tirtsa , Koren-Karie Nina , Mayseless Ofra , Aviezer Ora
Published: July 2002

To determine whether the transmission of attachment across generations is free from contextual constraints, adult attachment representations were assessed in two kibbutz settings, home-based and communal sleeping. It was hypothesised that under extreme child-rearing circumstances, such as the communal sleeping arrangement, the transmission of attachment is not evident, whereas in the more regular home-based environment the expected transmission of attachment will be found. The participants were 45 mothers and 45 infants, about equal numbers of boys and girls, from 20 kibbutz infant houses with communal sleeping arrangements, and from 25 kibbutz infant houses with home-based sleeping arrangements. Mothers were administered the Adult Attachment Interview (AAI), and infants were assessed through the Ainsworth Strange Situation. Among the home-based pairs, a correspondence of 76% was found between AAI and Strange Situation classifications, whereas the correspondence was only 40% in the communal sleeping group. It is argued that living in a communal sleeping arrangement reduces the expected transmission of attachment.
Competency, epistemology and pedagogy: curriculums holy trinity
Authors: Katz Steven
Published: July 2002

In this era of heightened calls for accountability and standards, clear visions of competence are more necessary than ever and, moreover, these planned products of education need explicit articulation. Such articulation falls within the purview of the formal curriculum and it is with this that the present article concerns itself. It draws on a past Ontario, Canada curricular initiative, The Common Curriculum, as the vehicle through which to examine the difficulties inherent in spelling out a conception of competence. Such difficulties, it is argued, stem from the inextricable link between definitions of competence and their associated epistemological and pedagogical implications.
Alcohol Intoxication and Violent Crime: Implications for Public Health Policy
Authors: McClelland Gary Michael , Teplin Linda A.
Published: July 2002

Despite extensive public health campaigns, the consequences of alcohol intoxication continue to be a serious public health concern. Alcohol intoxication, for example, is a prevalent feature of crime, especially violent crime. Previous studies of alcohol intoxication and violent crime have used samples of police reports, correctional populations (arrestees, jail detainees, or convicted offenders), or community surveys. Studies using police reports and correctional populations are biased because few police‐citizen encounters result in police reports or arrest. Community surveys avoid these biases but rely on the subject's assessment of both the victims' and the suspects' intoxication.

We took a different approach and directly observed 2,365 police‐citizen encounters. Observers used the Alcohol Symptom Checklist to determine the level of alcohol intoxication or impairment. We compared the prevalence of suspects' and victims' alcohol intoxication (equivalent to a blood alcohol level [BAL] of .05 or above) by type of encounter and computed odds ratios to assess the association between intoxication and type of encounter. We also controlled for demographic characteristics (race, gender, age, and socio‐economic status) to assess the relationships among perpetration, victimization, and intoxication. Overall, suspects are far more likely than victims to be intoxicated; not surprisingly, suspects in public order/vandalism encounters are the most likely to be intoxicated. Alcohol intoxication appears to contribute substantially to violent victimization. The role of alcohol intoxication is largest among groups that, if not intoxicated, are generally less vulnerable to violence: whites, males, and persons of higher socio‐economic status. We discuss the implications of these findings for services and public health policy.
Dialectical Behavior Therapy for Patients with Borderline Personality Disorder and Drug‐Dependence
Authors: Linehan Marsha M. , Schmidt Henry , Dimeff Linda A. , Craft J. Christopher , Kanter Jonathan , Comtois Katherine A.
Published: July 2002

A randomized clinical trial was conducted to evaluate whether Dialectical Behavior Therapy (DBT), an effective cognitive‐behavioral treatment for suicidal individuals with borderline personality disorder (BPD), would also be effective for drug‐dependent women with BPD when compared with treatment‐as‐usual (TAU) in the community. Subjects were randomly assigned to either DBT or TAU for a year of treatment. Subjects were assessed at 4, 8, and 12 months, and at a 16‐month follow‐up. Subjects assigned to DBT had significantly greater reductions in drug abuse measured both by structured interviews and urinalyses throughout the treatment year and at follow‐up than did subjects assigned to TAU. DBT also maintained subjects in treatment better than did TAU, and subjects assigned to DBT had significantly greater gains in global and social adjustment at follow‐up than did those assigned to TAU. DBT has been shown to be more effective than treatment‐as‐usual in treating drug abuse in this study, providing more support for DBT as an effective treatment for severely dysfunctional BPD patients across a range of presenting problems.