bluuebunny/crossref_metadata_2025 huggingface dataset:
Impulsivity in abstinent early‐ and late‐onset alcoholics: differences in self‐report measures and a discounting task
Authors: Dom G. , D’haene P. , Hulstijn W. , Sabbe B.
Published: December 2005

Aims  To test the hypothesis that early‐onset alcoholics (EOAs) can be differentiated from late‐onset alcoholics (LOAs) by more severe substance‐related problems and higher levels of impulsivity and aggression.

Design and measurements  A cross‐sectional patient survey with a community comparison group. The European Addiction Severity Index was used to assess substance‐related problems and the Barratt Impulsiveness Scale, the Dutch version of the Zuckermann Sensation Seeking Scale and the Buss–Durkee Hostility Inventory were used to assess impulsive and aggressive traits. Impulsive decision making was assessed using a delay discounting task (DDT) with hypothetical monetary rewards.

Participants and setting  Participants were EOAs (n = 42) and LOAs (n = 46) recruited from an addiction treatment centre and an unmatched, non‐substance‐abusing comparison group (n = 54).

Findings  The EOAs had higher levels of impulsive decision making than both the LOAs and the comparison group. The EOAs had higher scores than the LOAs on measures of impulsiveness, aggressiveness and the severity of substance‐related problems.

Conclusions  This study provides evidence that EOAs are more impulsive and aggressive than LOAs. Further identification of alcoholism subtypes based on dimensions of impulsivity should be considered in the light of their relationship with pharmacological and behavioural treatment interventions.
The relationship between patterns of alcohol use and mental and physical health disorders in two American Indian populations
Authors: O'Connell Joan , Novins Douglas K. , Beals Janette , Croy Calvin , Barón Anna E. , Spicer Paul , Buchwald Dedra ,   the American Indian Service Utilization, Psychiatric Epidemiology, Risk and Protective Factors Project Team
Published: December 2005

Aims First, define alcohol use categories among two reservation‐based American Indian (AI) populations based on the relationship between alcohol consumption and dependence. Secondly, examine associations between the alcohol use categories and other indicators of health status.

Design, participants and measurements Epidemiological data on 1287 AIs aged 18–57 years who consumed alcohol during the past year. CHAID tree analysis, a hierarchical partitioning method, was used to analyze alcohol quantity (highest number of drinks consumed during 1 day) and frequency (number of days drank during the past month) data to define quantity–frequency categories distinguished by differing rates of alcohol dependence. Multivariate analyses assessed relationships between the alcohol use categories thus identified and a number of health outcomes.

Findings People who reported drinking 12 or more drinks during 1 day and more than 4 days a month had the highest prevalence of alcohol dependence. Among the males who drank > 18 drinks the prevalence was 42.12% and among females who drank 12 or more drinks, 44.58%. The prevalence among males who drank > 18 drinks yet drank less frequently was also high (24.06%). Although findings differed by gender, drinkers in the highest risk category for alcohol dependence were most likely to report drug use disorders, mood/anxiety disorders, alcohol‐related physical disorders and lower quality of life.

Conclusions The quantity thresholds defined to identify AIs at highest risk for alcohol dependence in this study differed by gender and were higher than typically reported for non‐AIs. They are consistent with previous findings regarding the pattern of high‐quantity, low‐frequency alcohol consumption among AIs residing on reservations.
High‐resolution physical mapping and construction of a porcine contig spanning the intramuscular fat content QTL
Authors: Sato S. , Hasebe H. , Sato S. , Asahi Y. , Hayashi T. , Kobayashi E. , Sugimoto Y.
Published: December 2005

We previously mapped a locus for porcine intramuscular fat content (IMF) by linkage analysis to a 17.1‐cM chromosome interval on Sus scrofa chromosome 7 (SSC7) flanked by microsatellite markers SW1083 and SW581. In this study, we identified 34 microsatellite markers and 14 STSs from the 17.1‐cM IMF quantitative trait loci (QTL) region corresponding to HSA14q and aligned those loci using the INRA‐University of Minnesota porcine radiation hybrid (IMpRH) panel. We then constructed a 5.2‐Mb porcine bacterial artificial chromosome (BAC) contig of this region that was aligned using the RH panel. Finally, the IMF QTL was fine‐mapped to 12.6 cM between SJ169 and MM70 at the 0.1% chromosome‐wise significance level by genotyping the previously studied F2 resource family with 17 additional microsatellites. We also demonstrated that the SJ169–MM70 interval spans approximately 3.0 Mb and contains at least 12 genes: GALC, GPR65, KCNK10, SPATA7, PTPN21, FLJ11806, EML5, TTC8, CHES1, CAP2P1, CHORDC2P and C14orf143.
Mesoscale physical processes and the distribution and composition of ichthyoplankton on the southern Brazilian shelf break
Authors: FRANCO BÁRBARA CRISTIE , MUELBERT JOSÉ HENRIQUE , MATA MAURICIO MAGALHÃES
Published: December 2005

The southern Brazilian shelf supports the largest fish stocks in the country, and studies on physical–biological processes in the ecology of ichthyoplankton have been recommended to provide a better understanding of the variability of the recruitment of fishing resources. This study is the first to examine the influence of mesoscale physical processes on the distribution of early life stages of fish in this shelf‐break region. Collections of fish eggs and larvae and measurements of temperature and salinity were made at 13 stations along cross‐shelf transects in December 1997. Myctophidae, Bregmacerotidae, Clupeidae, Synodontidae and Engraulidae were the most abundant larvae in the northern region, while Engraulidae and Bregmacerotidae prevailed further south. In situ hydrographic data, NOAA/AVHRR images and merged TOPEX/POSEIDON + ERS‐1/2 satellite altimetry taken during the cruise revealed an anticyclonic eddy dominating the shelf around 31°S. Larval fish abundance was lower at the centre of this feature, suggesting that the eddy advected poorer offshore waters of tropical origin towards the inner shelf‐concentrating the larvae around the eddy.
Indirect ant‐protection against crab herbivory: damage‐induced susceptibility to crab grazing may lead to its reduction on ant‐colonized trees
Authors: OFFENBERG J. , MACINTOSH D. J. , NIELSEN M. G.
Published: December 2005

Mangrove trees colonized by weaver ants (Oecophylla smaragdina) experience less insect and crab herbivory compared with trees without ants. However, it is unlikely that ants prey on and deter crabs as they do insects. Protection could be indirect if leaves damaged by insects are more susceptible to crab herbivory.

In the field and in laboratory tests, leaves with artificial holes simulating leaf beetle‐feeding marks were more susceptible than intact leaves to damage by the crab Episesarma versicolor.

The study further revealed that damaged leaves showed increased susceptibility only to male crab feeding whereas females were indiscriminate, probably because of differences in claw morphology between the sexes.

Combined with previous findings at the same field site, these results suggest that ants can indirectly protect trees against crab herbivory by directly removing insect herbivores and thus decreasing the leaf damage they inflict. The system illustrates a complex trophic cascade involving density and trait‐mediated indirect interactions.
Solitary fibrous tumour and haemangiopericytoma: evolution of a concept
Authors: Gengler C , Guillou L
Published: December 2005

Haemangiopericytoma (HPC) was described in 1942 by Stout and Murray as a distinctive soft tissue neoplasm, presumably of pericytic origin, exhibiting a characteristic well‐developed ‘staghorn’ branching vascular pattern. Over the years, it appeared that this growth pattern was a non‐specific one, shared by numerous, unrelated benign and malignant lesions, and that HPC was better considered as a diagnosis of exclusion. Three categories of lesion may now be individualized within the heterogeneous group of HPC‐like neoplasms. The first category corresponds to those non‐HPC neoplasms that occasionally display HPC‐like features (e.g. synovial sarcoma). Lesions belonging to the second category show clear evidence of myoid/pericytic differentiation and correspond to true HPCs. They generally show a benign clinical course, and include glomangiopericytoma/myopericytoma, infantile myofibromatosis (previously called infantile HPC), and a subset of sinonasal HPCs. The third category is the solitary fibrous tumour (SFT) lesional group, which includes fibrous‐to‐cellular SFTs, and related lesions such as giant cell angiofibromas and lipomatous HPCs. In practice, any HPC‐like lesion can be allocated to one of these categories, leaving the ill‐defined ‘haemangiopericytoma’ category empty.
Gastrointestinal stromal tumours: an update
Authors: Rubin B P
Published: December 2005

Recently, there has been intense interest in the study of gastrointestinal stromal tumour (GIST); one might call it a virtual GIST revolution. This is due largely to the realization that most GISTs express KIT and harbour activating c‐KIT (KIT) or platelet‐derived growth factor receptor‐alpha (PDGFRA) receptor tyrosine kinase mutations that can be targeted by small molecule pharmacological inhibitors. Pathologists have benefited greatly from this revolution, mainly in the form of an improved ability to classify GISTs and, even more recently, in understanding the molecular underpinnings that underlie many fascinating clinical and pathological correlations. It is the purpose of this review to summarize recent developments in GIST classification and the molecular pathogenesis of GIST.
Positive effect of parathyroidectomy on bone mineral density in mild asymptomatic primary hyperparathyroidism*
Authors: HAGSTRÖM E. , LUNDGREN E. , MALLMIN H. , RASTAD J. , HELLMAN P.
Published: December 2005

Objectives.  Patients with mild primary hyperparathyroidism (pHPT) often appear asymptomatic, and have previously been regarded as not requiring treatment. However, increased cardiovascular morbidity and dyslipidaemia have also been recognized in mild pHPT, which also seem to be normalized after parathyroidectomy. The present study explores whether postmenopausal women with mild pHPT have decreased bone mineral density (BMD) compared with age‐matched healthy controls, and the effects on BMD of parathyroidectomy.

Design, Subjects and Intervention.  A population‐based health screening of 5202 postmenopausal women identified 87 overtly asymptomatic patients with mild pHPT as well as age‐matched healthy controls. A 5‐year follow‐up included 49 cases who had undergone parathyroidectomy. BMD was measured with DXA at the femoral neck, the lumbar spine and the total body.

Results.  At study entry, BMD was 5–6% lower in the lumbar spine (L2‐L4) and femoral neck in cases compared with matched controls. After the 5‐year follow‐up, BMD increased in L2‐L4 by 2.9% (P = 0.002) in the parathyroidectomized cases and remained stable in the femoral neck. However, femoral neck BMD increased 4.1% (P = 0.013) for cases <67 years old (50% of the cohort).

Conclusion.  In accordance with recent NIH guidelines for pHPT treatment, the level of BMD per se in the investigated group of patients justifies parathyroidectomy in almost half of the cases with mild pHPT. Surgery could be expected to increase BMD in L2‐L4 to the level of the controls, to increase femoral neck BMD in patients <67 years of age and to preserve femoral neck BMD in the elderly population.
Dissecting Ascaris glycosphingolipids for immunomodulatory moieties – the use of synthetic structural glycosphingolipid analogues
Authors: KEAN D. E. , OHTSUKA I. , SATO K. , HADA N. , TAKEDA T. , LOCHNIT G. , GEYER R. , HARNETT M. M. , HARNETT W.
Published: December 2005

We have previously shown glycosphingolipids of Ascaris suum to have phosphorylcholine (PC) and non‐PC immunomodulatory moieties. In the present study we further investigated the nature of the immunomodulatory moieties by employing three synthetic glycosphingolipids each possessing features of the original molecule to examine effects on macrophage and dendritic cell (DC) cytokine production and surface co‐stimulatory molecule expression. Compound 2, which lacked PC but contained ceramide, had no effect on either macrophages or DCs. Surprisingly however, Compound 1, which contained PC and hence arguably most resembled the native material, had, with the exception of a small increase in surface antigen expression, no immunomodulatory properties. Conversely, Compound 3, which contained PC but was otherwise least like the native molecule, demonstrated a number of effects on both macrophages and DCs, including induction of Th‐1/pro‐inflammatory cytokines, inhibition of such cytokines induced by IFN‐γ/LPS and increased expression of co‐stimulatory molecules. Taken together these results indicate: (i) that although PC is an immunomodulatory component of the native molecule other structural feature are necessary to allow it to act; (ii) that carbohydrate rather than ceramide is likely to represent a non‐PC immunomodulatory moiety; and (iii) that synthetic PC‐containing molecules have the potential to act as immunomodulatory drugs.
Genetic variation in resistance to repeated infections with Heligmosomoides polygyrus bakeri, in inbred mouse strains selected for the mouse genome project
Authors: BEHNKE J. M. , MUGAMBI J. M. , CLIFFORD S. , IRAQI F. A. , BAKER R. L. , GIBSON J. P. , WAKELIN D.
Published: December 2005

Since the publication of the mouse genome, attention has focused on the strains that were selected for sequencing. In this paper we report the results of experiments that characterized the response to infection with the murine gastrointestinal nematode Heligmosomoides polygyrus of eight new strains (A/J, C57BL/6, C3H, DBA/2, BALB/c, NIH, SJL and 129/J), in addition to the well‐characterized CBA (poor responder) and SWR (strong responder) as our controls. We employed the repeated infection protocol (consisting of 7 superimposed doses of 125L3 each administered at weekly intervals, faecal egg counts in weeks 2, 4 and 6 and assessment of worm burdens in week 6) that was used successfully to identify quantitative trait loci for genes involved in resistance to H. polygyrus. SWR, SJL and NIH mice performed indistinguishably and are confirmed as strong responder strains to H. polygyrus. CBA, C3H and A/J mice all tolerated heavy infections and are assessed as poor responders. In contrast, DBA/2, 129/J and BALB/c mice performed variably between experiments, some tolerating heavy worm burdens comparable to those in poor responders, and some showing evidence of resistance, although only in one experiment with female 129/J females and one with female BALB/c was the pattern and extent of worm loss much like that in SWR mice. Because the genetic relationships between six of the strains exploited in this study are now well‐understood, our results should enable analysis through single nucleotide polymorphisms and thereby provide more insight into the role of the genes that control resistance to H. polygyrus.
Antibodies enhance the protective effect of CD4+ T lymphocytes in SCID mice perorally infected with Encephalitozoon cuniculi
Authors: SAK B. , SALÁT J. , HORKÁ H. , SAKOVÁ K. , DITRICH O.
Published: December 2005

The role of antibodies in the immune response to microsporidiosis was studied using a novel anti‐exospore monoclonal antibody (MAb) P5/H1, which recognizes surface antigens of Encephalitozoon cuniculi. The effect of the MAb on microsporidial infection in vivo was to prolong the survival of previously CD4+ reconstituted, perorally infected and intraperitoneally MAb‐treated SCID mice. The MAb decreased the numbers of E. cuniculi spores in peritoneal smears obtained post mortem. These results suggest a possible role for antibodies in protection against perorally acquired E. cuniculi infection.
The maize viviparous15 locus encodes the molybdopterin synthase small subunit
Authors: Suzuki Masaharu , Mark Settles A. , Tseung Chi‐Wah , Li Qin‐Bao , Latshaw Susan , Wu Shan , Porch Timothy G. , Schmelz Eric A. , James Martha G. , McCarty Donald R.
Published: December 2005

A new Zea mays viviparous seed mutant, viviparous15 (vp15), was isolated from the UniformMu transposon‐tagging population. In addition to precocious germination, vp15 has an early seedling lethal phenotype. Biochemical analysis showed reduced activities of several enzymes that require molybdenum cofactor (MoCo) in vp15 mutant seedlings. Because MoCo is required for abscisic acid (ABA) biosynthesis, the viviparous phenotype is probably caused by ABA deficiency. We cloned the vp15 mutant using a novel high‐throughput strategy for analysis of high‐copy Mu lines: We used MuTAIL PCR to extract genomic sequences flanking the Mu transposons in the vp15 line. The Mu insertions specific to the vp15 line were identified by in silico subtraction using a database of MuTAIL sequences from 90 UniformMu lines. Annotation of the vp15‐specific sequences revealed a Mu insertion in a gene homologous to human MOCS2A, the small subunit of molybdopterin (MPT) synthase. Molecular analysis of two allelic mutations confirmed that Vp15 encodes a plant MPT synthase small subunit (ZmCNX7). Our results, and a related paper reporting the cloning of maize viviparous10, demonstrate robust cloning strategies based on MuTAIL‐PCR. The Vp15/CNX7, together with other CNX genes, is expressed in both embryo and endosperm during seed maturation. Expression of Vp15 appears to be regulated independently of MoCo biosynthesis. Comparisons of Vp15 loci in genomes of three cereals and Arabidopsis thaliana identified a conserved sequence element in the 5′ untranslated region as well as a micro‐synteny among the cereals.
The maize Viviparous10/Viviparous13 locus encodes the Cnx1 gene required for molybdenum cofactor biosynthesis
Authors: Porch Timothy G. , Tseung Chi‐Wah , Schmelz Eric A. , Mark Settles A.
Published: December 2005

Abscisic acid (ABA), auxin and nitrate are important signaling molecules that affect plant growth responses to the environment. The synthesis or metabolism of these compounds depends on the molybdenum cofactor (MoCo). We show that maize (Zea mays) viviparous10 (vp10) mutants have strong precocious germination and seedling lethal phenotypes that cannot be rescued with tissue culture. We devised a novel PCR‐based method to clone a transposon‐tagged allele of vp10, and show that Vp10 encodes the ortholog of Cnx1, which catalyzes the final common step of MoCo synthesis. The seedling phenotype of vp10 mutants is consistent with disruptions in ABA and auxin biosynthesis, as well as a disruption in nitrate metabolism. Levels of ABA and auxin are reduced in vp10 mutants, and vp10 seedlings lack MoCo‐dependent enzyme activities that are repairable with exogenous molybdenum. vp10 and an Arabidopsis cnx1 mutant, chlorate6 (chl6), have similar defects in aldehyde oxidase (AO) enzyme activity, which is required for ABA synthesis. Surprisingly, chl6 mutants do not show defects in abiotic stress responses. These observations confirm an orthologous function for Cnx1 and Vp10, as well as defining a characteristic viviparous phenotype to identify other maize cnx mutants. Finally, the vp10 mutant phenotype suggests that cnx mutants can have auxin‐ as well as ABA‐biosynthesis defects, while the chl6 mutant phenotype suggests that low levels of AO activity are sufficient for normal abiotic stress responses.
Using ‘mute’ plants to translate volatile signals
Authors: Paschold Anja , Halitschke Rayko , Baldwin Ian T.
Published: December 2005

When attacked by herbivores, plants release volatile organic compounds (VOCs) that attract natural enemies of the herbivores and function as indirect defenses. Whether or not neighboring plants ‘eavesdrop’ on these VOCs remains controversial because most studies use unrealistic experimental conditions and VOC exposures. In order to manipulate exposures of wild‐type (WT) Nicotiana attenuata‘receiver’ plants, we elicited transformed ‘emitter’ plants, whose production of herbivore‐induced C6 green leaf volatiles (GLVs) or terpenoid volatiles was genetically silenced, and placed them up‐wind of WT ‘receiver’ plants in open‐flow experimental chambers. We compared the transcriptional and secondary metabolite defense responses of WT receiver plants exposed to VOCs from these transgenic emitter plants with those of plants exposed to VOCs from WT emitter plants. No differences in the constitutive accumulation of defense metabolites and the signal molecule jasmonic acid (JA) were found. Additional elicitation of receiver plants revealed that exposure to WT, GLV‐deficient and terpenoid‐deficient volatile blends did not prime induced defenses, JA accumulation, or the expression of lipoxygenase 3 (NaLOX3), a gene involved in JA biosynthesis. However, exposure to wound‐ and herbivore‐induced VOCs significantly altered the transcriptional patterns in receiver plants. We identified GLV‐dependent genes by complementing the GLV‐deficient volatile blend with a mixture of synthetic GLVs. Blends deficient in GLVs or cis‐α‐bergamotene regulated numerous genes in receiver plants that did not respond to the complete VOC blends of WT emitters, indicating a suppressive effect of GLVs and terpenoids. Whether these transcriptional responses translate into changes in plant fitness in nature remains to be determined.
Atypical Cyclopia in a Brown Swiss Cross Calf: A Case Report
Authors: ÖZcan K. , Gürbulak K. , Takçi̇ İ. , ÖZen H. , Kaçar C. , Pancarci̇ M. Ş.
Published: December 2005

In this report, an atypical form of cyclopia is described in a stillborn Brown Swiss cross male calf. The changes were confined to the head. The most significant malformation was the presence of a median orbita‐like opening that did not contain an eyeball. Other defects included prosencephalic aplasia, brachygnathia superior and arrhinia. The possible cause of this congenital defect could not be ascertained.
Contribution of baroreflex sensitivity and vascular reactivity to variable haemodynamic responses to cocaine in conscious rats
Authors: Traub Michael , Aochi Tamiko , Kawada Toru , Shishido Toshiaki , Sunagawa Kenji , Knuepfer Mark M
Published: December 2005

1. Baroreflex function is critical for short‐term arterial pressure regulation and decreased baroreflex responsivity may predict a predisposition to hypertension and sudden cardiac death. In the present study, we assessed whether baroreflex sensitivity (BRS) and/or vascular reactivity covary with haemodynamic responsiveness to cocaine in vascular and mixed responders.

2. We assessed the heart rate index of BRS in resting animals. We examined dose–response relationships to pressor and depressor agents to determine cardiovascular reactivity. Subsequently, rats were given cocaine (5 mg/kg, i.v.) to classify them as vascular or mixed responders. Vascular responders (n = 16) were defined as those rats with a substantial (> 8%) decrease in cardiac output in response to cocaine owing to a larger increase in systemic vascular resistance. The remaining rats (n = 8) were mixed responders because they had smaller increases in vascular resistance and little change or an increase in cardiac output.

3. The BRS determined with angiotensin (Ang) II, but not with phenylephrine, was impaired in mixed responders compared with vascular responders. At equipressor doses, there were significantly greater reductions in cardiac output in vascular responders compared with mixed responders in response to phenylephrine or AngII. Methacholine produced greater decreases in heart rate in vascular responders, suggesting greater muscarinic responsivity.

4. We conclude that differences in vascular reactivity to AngII may contribute to differences in haemodynamic response profiles to cocaine in individual rats. More importantly, the differences in vascular responsivity and BRS do not appear to be primary determinants of haemodynamic response variability.
Individualized drug and dose: The clinical pharmacologist's calling or curse?
Authors: Begg EJ
Published: December 2005

1. The role of the clinical pharmacologist is to promote the rational, safe and effective use of medicines. This revolves around the notion of variability, between and within patients and between and within drugs, in terms of both pharmacokinetics and pharmacodynamics. Ideal therapeutics involves tailoring the drug and its dosing to the individual patient, taking into account this variability.

2. In the 25 years of my membership of the Australasian Society of Clinical and Experimental Pharmacologists and Toxicologists, three themes have dominated my research: (i) drugs and breast feeding; (ii) aminoglycoside dosing; and (iii) pharmacogenetics. In all these, the research has been orientated towards identifying factors involved in variability and working towards dose individualization based on the understanding of these factors.

3. Our model for predicting drug concentrations in milk has assisted not only in estimating the safety of drug ingestion via breast milk, but also in the understanding of the processes involved in drug transfer.

4. The aminoglycoside studies have assisted in the understanding of the basis behind extended interval dosing, leading to a model for dose prediction that is widely used, especially in Australasia.

5. Pharmacogenetics is a field widely acclaimed as having a huge future in terms of individualization of drug therapy. Our early studies in this area lend only cautious support to this optimism.
G‐Protein‐coupled receptor–protein interactions: Basis for new concepts on receptor structure and function
Authors: Tilakaratne Nanda , Sexton Patrick M
Published: December 2005

1. G‐Protein‐coupled receptors (GPCRs) constitute a large family of cell surface proteins. Their primary function is to transmit extracellular stimuli to intracellular signals. It is estimated that the human genome contains more than 1000 genes that code for proteins of the GPCR structure. These receptors also comprise the most important class of therapeutic drug targets.

2. The mechanism of GPCR signalling was initially envisioned as involving coupling to the heterotrimeric G‐proteins only. However, recent developments in the field suggest that such a simplistic model cannot be sustained any longer. The emerging view is that a wide range of accessory proteins are involved in the regulation of every aspect of GPCR activity.

3. G‐Protein‐coupled receptor‐interacting proteins are implicated in the regulation of several aspects of GPCR biology, including receptor targeting to the respective sites of action, receptor anchoring, signalling and receptor desensitization. In some cases (e.g. receptor activity modifying proteins), they may contribute to the receptor structure and form a part of the ligand‐binding domain.

4. These findings have contributed to new concepts of cellular organization in which modular protein–protein interactions provide a network through which signalling pathways are assembled and controlled.
New strategies for the medical treatment of prostate cancer
Authors: ISAACS JOHN T.
Published: December 2005

Androgen is a major growth factor in the normal prostate and determines the overall number of prostate cells. Metastatic prostate cancer, while initially responsive to androgen ablation, eventually becomes hormone‐refractory and resistant to many treatments. Unfortunately, there are very few agents in the preclinical stage with a seemingly promising future for hormone‐refractory prostate cancer (HRPC) that are actually taken through the complete drug development process, including US Food and Drug Administration approval. Many novel strategies under investigation for treating HRPC target metastatic prostate cancer cells that are neither androgen‐dependent nor in the proliferative state. Examples of therapies that target this so‐called ‘Achilles’ heel’ of HRPC include immune therapy, gene therapy, angiogenesis inhibition, and activation of programmed cell death. Unique properties of HRPC allow for the development of novel treatments that target prostate‐specific antigen (PSA), human glandular kallikrein‐2, or prostate‐specific membrane antigen. An inactive prodrug with a thapsigargin analogue, a sesquiterpene lactone from the plant Thapsia garganica, is currently under investigation specifically for the targeted therapy of HRPC. Preclinical data suggest the PSA‐targeting abilities of this novel therapy are associated with a nearly complete cessation of tumour growth with minimal toxicity.
Therapeutic options in androgen‐independent prostate cancer: building on docetaxel
Authors: PETRYLAK DANIEL
Published: December 2005

Of men with metastatic prostate cancer who undergo androgen ablation, 70–80% respond rapidly to therapy, as manifested by a reduction in prostate cancer‐related symptoms and declines in serum prostate‐specific antigen (PSA) level. Unfortunately, after a median of 18–24 months, nearly all patients with metastatic prostate cancer will progress to androgen independence. Until recently the standard of care for treating hormone‐refractory prostate cancer (HRPCa) was the combination of mitoxantrone and prednisone, which palliated bone pain but did not extend survival. Two randomized trials with > 1700 patients showed for the first time a survival benefit for patients with HRPC treated with chemotherapy; when compared with mitoxantrone‐based therapy, docetaxel based‐therapy reduced the risk of death by 20–24%. Future trials in HRPC are attempting to improve the efficacy of docetaxel by incorporating new agents targeting angiogenesis, apoptosis, and signal transduction pathways; there is promising activity for these novel combinations in phase I and II studies. Concepts are also being refined about definitions of response and progressive disease, patient eligibility criteria, and the validity of surrogate markers of efficacy and survival, as shown by changes in PSA level.
Why girls say ‘holded’ more than boys
Authors: Hartshorne Joshua K. , Ullman Michael T.
Published: December 2005

Women are better than men at verbal memory tasks, such as remembering word lists. These tasks depend on declarative memory. The declarative/procedural model of language, which posits that the lexicon of stored words is part of declarative memory, while grammatical composition of complex forms depends on procedural memory, predicts a female superiority in aspects of lexical memory. Other neurocognitive models of language have not made this prediction. Here we examine the prediction in past‐tense over‐regularizations (e.g. holded) produced by children. We expected that girls would remember irregular past‐tense forms (held) better than boys, and thus would over‐regularize less. To our surprise, girls over‐regularized far more than boys. We investigated potential explanations for this sex difference. Analyses showed that in girls but not boys, over‐regularization rates correlated with measures of the number of similar‐sounding regulars (folded, molded). This sex difference in phonological neighborhood effects is taken to suggest that girls tend to produce over‐regularizations in associative lexical memory, generalizing over stored neighboring regulars, while boys are more likely to depend upon rule‐governed affixation (hold+‐ed). The finding is consistent with the hypothesis that, likely due to their superior lexical abilities, females tend to retrieve from memory complex forms (walked) that men generally compose with the grammatical system (walk+‐ed). The results suggest that sex may be an important factor in the acquisition and computation of language.
Toddler subtraction with large sets: further evidence for an analog‐magnitude representation of number
Authors: Slaughter Virginia , Kamppi Dorian , Paynter Jessica
Published: December 2005

Two experiments were conducted to test the hypothesis that toddlers have access to an analog‐magnitude number representation that supports numerical reasoning about relatively large numbers. Three‐year‐olds were presented with subtraction problems in which initial set size and proportions subtracted were systematically varied. Two sets of cookies were presented and then covered. The experimenter visibly subtracted cookies from the hidden sets, and the children were asked to choose which of the resulting sets had more. In Experiment 1, performance was above chance when high proportions of objects (3 versus 6) were subtracted from large sets (of 9) and for the subset of older participants (older than 3 years, 5 months; n= 15), performance was also above chance when high proportions (10 versus 20) were subtracted from the very large sets (of 30). In Experiment 2, which was conducted exclusively with older 3‐year‐olds and incorporated an important methodological control, the pattern of results for the subtraction tasks was replicated. In both experiments, success on the tasks was not related to counting ability. The results of these experiments support the hypothesis that young children have access to an analog‐magnitude system for representing large approximate quantities, as performance on these subtraction tasks showed a Weber's Law signature, and was independent of conventional number knowledge.
Young children make scale errors when playing with dolls
Authors: Ware Elizabeth A. , Uttal David H. , Wetter Emily K. , DeLoache Judy S.
Published: December 2005

Prior research (

DeLoache, Uttal & Rosengren, 2004

) has documented that 18‐ to 30‐month‐olds occasionally make scale errors: they attempt to fit their bodies into or onto miniature objects (e.g. a chair) that are far too small for them. The current study explores whether scale errors are limited to actions that directly involve the child's body. We investigated whether children would also make scale errors with a doll and objects that were much too small for the doll (e.g. a chair, a bed). Many participants did try to fit the doll into or onto the miniature objects. Thus, the previously documented phenomenon of scale errors extends to situations in which the relevant size difference is between two objects. This finding supports the view that scale errors occur when visual information about object size fails to influence the decision to act on an object. The results are discussed in terms of the use of visual information for the planning and control of actions.
How fantasy benefits young children's understanding of pretense
Authors: Sobel David M.
Published: December 2005

Sobel and Lillard (2001) demonstrated that 4‐year‐olds’ understanding of the role that the mind plays in pretending improved when children were asked questions in a fantasy context. The present study investigated whether this fantasy effect was motivated by children recognizing that fantasy contains violations of real‐world causal structure. In Experiment 1, 4‐year‐olds were shown a fantasy character engaged in ordinary actions or actions that violated causal knowledge. Children were more likely to say that a troll doll who was acting like but ignorant of the character was not pretending to be that character when read the violation story. Experiment 2 suggested that this difference was not caused by a greater interest in the violation story. Experiment 3 demonstrated a similar difference for characters engaged in social and functional violations that were possible in the real world. These data are consistent with the hypothesis that preschoolers use actions and appearance more than mental states to make judgments about pretense, but that those judgments can be influenced by the context in which the questions are presented.
Germs and angels: the role of testimony in young children's ontology
Authors: Harris Paul L. , Pasquini Elisabeth S. , Duke Suzanne , Asscher Jessica J. , Pons Francisco
Published: December 2005

In three experiments, children's reliance on other people's testimony as compared to their own, first‐hand experience was assessed in the domain of ontology. Children ranging from 4 to 8 years were asked to judge whether five different types of entity exist: real entities (e.g. cats, trees) whose existence is evident to everyone; scientific entities (e.g. germs, oxygen) that are normally invisible but whose existence is generally presupposed in everyday discourse; endorsed beings (e.g. the Tooth Fairy, Santa Claus) whose existence is typically endorsed in discourse with young children; equivocal beings (e.g. monsters, witches) whose existence is not typically endorsed in discourse with young children; and impossible entities (e.g. flying pigs, barking cats) that nobody believes in. Children make a broad dichotomy between entities and beings that they claim to exist (real entities; scientific entities; and endorsed beings) and those whose existence they deny (equivocal beings and impossible entities). They also make a more fine‐grained distinction among the invisible entities that they claim to exist. Thus, they assert the existence of scientific entities such as germs with more confidence than that of endorsed beings such as Santa Claus. The findings confirm that children's ontological claims extend beyond their first‐hand encounters with instances of a given category. Children readily believe in entities that they cannot see for themselves but have been told about. Their confidence in the existence of those entities appears to vary with the pattern of testimony that they receive.
Socrates in the Platonic Dialogues
Authors: Osborne Catherine
Published: December 2005

If Socrates is portrayed holding one view in one of Plato's dialogues and a different view in another, should we be puzzled? If (as I suggest) Plato's Socrates is neither the historical Socrates, nor a device for delivering Platonic doctrine, but a tool for the dialectical investigation of a philosophical problem, then we should expect a new Socrates, with relevant commitments, to be devised for each setting. Such a dialectical device – the tailor‐made Socrates – fits with what we know of other contributions to the genre of the Sokratikos Logos, to which Plato was neither the first nor the only contributor.
The Unity of Language and Logic in Wittgenstein's Tractatus
Authors: Cheung Leo K. C.
Published: December 2005

The purpose of this paper is to offer an interpretation of the Tractatus’ proof of the unity of logic and language. The kernel of the proof is the thesis that the sole logical constant is the general propositional form. I argue that the Grundgedanke, the existence of the sole fundamental operation N and the analyticity thesis, together with the fact that the operation NN can always be seen as having no specific formal difference between its result and its base, imply that NN is intrinsic to every elementary proposition. I also argue that the picture theory of proposition is an account of the generation of propositions via naming, and that its crucial idea is that naming is the instantiation of the form of a name, which consists in arbitrarily picking out an object as the meaning of the name from those objects sorted out by the form of the name. It follows that the existential quantifier, that is, NN, is intrinsic to naming (and therefore to every elementary proposition). It is then proven that the sole logical constant is the general propositional form. This, together with the truth‐functionality of logical necessity, implies that logic and language are unified via a general rule – logical syntax.
Spillovers from Foreign Firms through Worker Mobility: An Empirical Investigation*
Authors: Görg Holger , Strobl Eric
Published: December 2005

While there is a large empirical literature on productivity spillovers from multinationals, this literature treats the channels through which these spillover effects work as a black box. The new approach in this paper is to investigate whether spillovers occur via worker mobility. We use data on whether or not the owner of a domestic firm has previous experience in a multinational, and relate this information to firm‐level productivity. Our results suggest that firms which are run by owners who worked for multinationals in the same industry immediately prior to opening up their own firm are more productive than other domestic firms.
Moore's Law and the Semiconductor Industry: A Vintage Model*
Authors: Aizcorbe Ana , Kortum Samuel
Published: December 2005

In this paper we develop a vintage model to gain a better understanding of the semiconductor industry and its role in recent U.S. productivity gains. Unlike previous work, in our model the observed price declines of individual chips are driven by the introduction of better vintages rather than by learning economies. Dominated chips, nonetheless, continue to be produced, for a time, due to sunk investments in chip‐specific production equipment. The model lends partial support to Jorgenson's hypothesis that an exogenous increase in Moore's Law could have generated the more rapid price declines, and faster productivity growth, seen after 1995.
Information Technology and the World Economy*
Authors: Jorgenson Dale W. , Vu Khuong
Published: December 2005

This paper addresses the impact of investment in information technology (IT) on the recent resurgence of world economic growth. We describe the growth of the world economy, seven regions and 14 major economies during the period 1989–2003. We allocate the growth of world output between input growth and productivity and find, surprisingly, that input growth greatly predominates! The contributions of IT investment have increased in all regions, but especially in industrialized economies and Developing Asia. Differences in per capita output are explained by differences in per capita input, rather than by variations in productivity.
Panel‐data Estimates of the Production Function and the Revenue Function: What Difference Does It Make?*
Authors: Mairesse Jacques , Jaumandreu Jordi
Published: December 2005

The lack of individual firm information on output prices is a major problem in the econometrics of production. In particular, it may be expected to account for a significant share of the large discrepancies found between the cross‐sectional and time‐series estimates of capital and scale elasticities. However, taking advantage of two panel‐data samples for which we had such information, we find that estimating the revenue function (using a nominal output measure) or the production function proper (using a real output measure) makes very little difference for our results. The biases due to other sources of specification errors are probably more important.
New Mothers’ Employment and Public Policy in the UK, Germany, the Netherlands, Sweden, and Japan
Authors: Kenjoh Eiko
Published: December 2005

Abstract. This paper investigates the link between family‐friendly policies and women's employment after birth of the first child in the UK, Germany, the Netherlands, Sweden, and Japan in the 1980s and the 1990s. Our econometric analyses use household panel data from each of the five countries: BHPS, GSOEP, OSA, HUS, and JPSC, respectively. Public policies that facilitate the combination of motherhood and paid employment offer an effective means in increasing the participation rate of first‐time mothers. The results also indicate that the availability and stimulation of good‐quality part‐time employment can provide additional, strong incentives for new mothers to enter active employment.
Anterior cingulate activity correlates with blood pressure during stress
Authors: Gianaros Peter J. , Derbtshire Stuart W.G. , May J. Christopher , Siegle Greg J. , Gamalo Mark A. , Jennings J. Richard
Published: December 2005

The anterior cingulate cortex presumptively regulates blood pressure reactions to behavioral stressors. There is little evidence in humans, however, that stressor‐evoked changes in blood pressure correlate with concurrent changes in anterior cingulate activity. Using fMRI, we tested whether changes in mean arterial blood pressure correlate with ongoing changes in blood oxygen level dependent (BOLD) activation in 9 women and 11 men who completed a stressful Stroop color‐word interference task. Higher mean arterial pressure during the Stroop task correlated with greater BOLD activation in two regions of the cingulate cortex (perigenual and mid‐anterior) and in other networked brain regions, including the insula, thalamus, and periaqueductal gray. These results support the hypothesis that the anterior cingulate cortex regulates blood pressure reactions to behavioral stressors in humans.
Gliotoxin non‐selectively induces apoptosis in fibrotic and normal livers
Authors: Hagens Werner I. , Olinga Peter , Meijer Dirk K. F. , Groothuis Geny M. M. , Beljaars Leonie , Poelstra Klaas
Published: December 2005

Abstract: Background: Liver fibrosis is the common response to chronic liver injury, ultimately leading to cirrhosis. Several lines of evidence indicate that inducing apoptosis of hepatic stellate cells (HSC) may lead to regression of liver fibrosis. Recently, it was shown that gliotoxin (GTX) induces apoptosis of HSC. However, the clinical use of GTX may be limited because of the lack of cell and tissue specificity, causing a high risk of potentially severe adverse effects. The aim of this study, therefore, was to study the effect of GTX on different cells of the liver.

Methods: We used normal and fibrotic precision‐cut rat liver slices to study the effect of GTX on the various resident liver cell types. In these slices, the complex cell–cell interactions are preserved, which closely mimics the in vivo situation.

Results: GTX exhibited a potent apoptosis‐inducing activity in these slices. Both immunohistochemical stainings and real‐time mRNA techniques showed that this apoptosis‐inducing effect was seen in HSC. However, Kupffer cells and liver endothelial cells were also affected by GTX, whereas hepatocytes were only mildly affected.

Conclusions: This study indicates that the apoptosis‐inducing strategy to treat liver fibrosis has high potential, but it will be necessary to develop an HSC‐specific therapy to prevent adverse effects.
Myotilin is not the Causative Gene for Vocal Cord and Pharyngeal Weakness with Distal Myopathy (VCPDM)
Authors: Garvey Sean M. , Senderek Jan , Beckmann Jacques S. , Seboun Eric , Jackson Charles E. , Hauser Michael A.
Published: December 2005

Myotilin (MYOT) is a promising candidate gene for Vocal Cord and Pharyngeal Weakness with Distal Myopathy (VCPDM, also known as MPD2). Located within the minimum VCPDM candidate interval, myotilin mutations also cause a similarly progressive and adult‐onset muscle disease. We examined myotilin in VCPDM patients by sequence analysis, RT‐PCR, Southern blotting, and western blotting. We detected no defects in the myotilin gene, transcript, or protein in VCPDM. We also report several useful SNPs and STRs for the analysis of myotilin in muscle diseases of suspected, yet unknown genetic origin. We conclude that MYOT mutations likely are not a cause of VCPDM.