bluuebunny/crossref_metadata_2025 huggingface dataset:
Acute leptin deficiency, leptin resistance, and the physiologic response to leptin withdrawal
Authors: Montez Jason M. , Soukas Alex , Asilmaz Esra , Fayzikhodjaeva Gulnorakhon , Fantuzzi Giamila , Friedman Jeffrey M.
Published: February 2005

Food restriction and weight loss result in reduced plasma leptin, which is associated with a pleiotropic biologic response. However, because weight loss itself is also associated with changes in numerous other humoral and metabolic signals, it can be difficult to determine the precise features of the biologic response to acute leptin deficiency. To study this response in the absence of changes in nutritional state, we have developed a protocol that allows such analysis in normal, non-food-restricted animals. Wild-type mice are treated with high-dose leptin until fat mass is depleted and, as a consequence, endogenous leptin production is reduced. At this point, exogenous leptin is abruptly withdrawn, thus inducing a state of leptin deficiency in otherwise normal mice. Leptin deficiency is sustained by feeding the animals only as much as they consumed voluntarily before leptin withdrawal. The biologic response to leptin deficiency induced in this manner includes altered neuropeptide levels, decreased energy expenditure, and impaired reproductive and immune function. Replacement of leptin at physiological concentrations after withdrawal of high-dosage leptin blunts, but does not completely block, the hyperphagia and weight regain caused by acute leptin deficiency, nor does it correct the resulting reproductive and immune dysfunction. This suggests that high-dosage leptin treatment induces a state of partial leptin resistance. In aggregate, these studies establish the role of acute hypoleptinemia in regulating energy balance, the immune system, and reproductive function, and further suggest that high-dosage leptin treatment can induce a state of acquired leptin resistance.
A previously uncharacterized role for small protein B (SmpB) in transfer messenger RNA-mediated trans-translation
Authors: Sundermeier Thomas R. , Dulebohn Daniel P. , Cho Hye Jin , Karzai A. Wali
Published: February 2005

SsrA is a versatile RNA molecule found in all bacteria that functions as both a tRNA and an mRNA. SsrA rescues ribosomes stalled on damaged mRNAs and directs the tagging and degradation of their aberrant protein products. Small protein B (SmpB) is required for all known activities of SsrA. The two known functions of SmpB are binding SsrA RNA and promoting stable association of the SmpB·SsrA complex with 70S ribosomes. Using mutational analysis and biochemical experiments, we have discovered a previously uncharacterized SmpB function. This function is required for a step in the tagging process downstream of SsrA binding and ribosome association but before transpeptidation of the SsrA-linked alanine and establishment of the SsrA reading frame. Our results clearly demonstrate that residues in the C-terminal tail of SmpB confer a hitherto unrevealed function that is essential for trans-translation. Based on these results, we propose that upon binding stalled ribosomes, the unstructured C-terminal tail of SmpB acquires contacts that are critical for productive accommodation of SsrA into the ribosomal A site.
The identification of
Hoxc8
target genes
Authors: Lei Haiyan , Wang Hailong , Juan Aster H. , Ruddle Frank H.
Published: February 2005

Hox
genes encode transcription factors that control spatial patterning during embryogenesis. To date, downstream targets of
Hox
genes have proven difficult to identify. Here, we describe studies designed to identify target genes under the control of the murine transcription factor
Hoxc8
. We used a mouse 16,463 gene oligonucleotide microarray to identify mRNAs whose expression was altered by the overexpression of
Hoxc8
in C57BL/6J mouse embryo fibroblasts (MEF) in cell culture (
in vitro
). We identified a total of 34 genes whose expression was changed by 2-fold or greater: 16 genes were up-regulated, and 18 genes were down-regulated. The majority of genes encoded proteins involved in critical biological processes, such as cell adhesion, migration, metabolism, apoptosis, and tumorigenesis. Two genes showed high levels of regulation: (
i
) secreted phosphoprotein 1 (
Spp1
), also known as osteopontin (
OPN
), was down-regulated 4.8-fold, and (
ii
) frizzled homolog 2 (
Drosophila
) (
Fzd2
) was up-regulated 4.4-fold. Chromatin immunoprecipitation (ChIP) analysis confirmed the direct interaction between the
OPN
promoter and Hoxc8 protein
in vivo
, supporting the view that
OPN
is a direct transcriptional target of
Hoxc8
.
A Mendelian locus on chromosome 16 determines susceptibility to doxorubicin nephropathy in the mouse
Authors: Zheng Zongyu , Schmidt-Ott Kai M. , Chua Streamson , Foster Kirk A. , Frankel Rachelle Z. , Pavlidis Paul , Barasch Jonathan , D'Agati Vivette D. , Gharavi Ali G.
Published: February 2005

The development of kidney disease is influenced by both genetic and environmental factors. Searching for models of glomerulopathy that display strong gene–environment interaction, we examined the determinants of anthracycline-induced nephropathy, a classic, strain-dependent experimental model applied to rodents in the past four decades. We produced three crosses derived from mice with contrasting susceptibility to doxorubicin (DOX) nephropathy and, surprisingly, we found that this widely studied model segregates as a single-gene defect with recessive inheritance. By genome-wide analysis of linkage, we mapped the trait locus to chromosome 16A1-B1 (
DOXNPH
locus) in all three crosses [peak logarithm of odds (lod) score of 92.7,
P
= 1 × 10
-65
]; this interval represents a susceptibility locus for nephropathy. Gene expression analysis indicated that susceptibility alleles at the
DOXNPH
locus are associated with blunted expression of protein arginine methyltransferase 7 (Prmt7) on chromosome 8, a protein previously implicated in cellular sensitivity to chemotherapeutic agents (lod = 12.4,
P
= 0.0001). Therefore, Prmt7 expression serves as a molecular marker for susceptibility to DOX nephropathy. Finally, increased variation in the severity of kidney disease among affected mice motivated a second genome-wide search, identifying a locus on chromosome 9 that influences the severity and progression of nephropathy (
DOXmod
, peak lod score 4.3,
P
= 0.0018). These data provide genetic and molecular characterization of a previously unrecognized Mendelian trait. Elucidation of DOX nephropathy may simultaneously provide insight into the pathogenesis of renal failure and mechanisms of cytotoxicity induced by chemotherapeutic agents.
Using a baculovirus display library to identify MHC class I mimotopes
Authors: Wang Yibing , Rubtsov Anatoyla , Heiser Ryan , White Janice , Crawford Frances , Marrack Philippa , Kappler John W.
Published: February 2005

We have developed a baculovirus-based display system for identifying antigen mimotopes for MHC class I-specific T cells. The mouse MHC class I molecule, Dd, was displayed on baculovirus-infected insect cells with a library of 9- and 10-mer peptides tethered via a flexible linker to the N terminus of β2 microglobulin. As a test case, the library was screened by flow cytometry by using a multimeric fluorescent αβTCR from a mouse T cell specific for Ddplus an unknown self peptide. A mimotope was identified that, when bound to Dd, stimulated the T cell to secret IL-2. The sequence of the mimotope was used to identify a self peptide present in a mouse protein, Spin. The Spin peptide, when complexed with Dd, also activated the T cell. This technique should be generally useful in identifying and manipulating MHC class I peptide mimotopes and epitopes.
Toll-like receptor 4 polymorphisms are associated with resistance to Legionnaires' disease
Authors: Hawn Thomas R. , Verbon Annelies , Janer Marta , Zhao Lue Ping , Beutler Bruce , Aderem Alan
Published: February 2005

The immunogenetic factors that influence susceptibility to pneumonia are poorly understood. Recent studies suggest an association of toll-like receptor 4 (TLR4) polymorphisms with increased susceptibility to some infections. Here, we examined whether polymorphisms in TLR4 influence susceptibility to Legionnaires' disease (LD) by using a case-control study to compare the allele frequencies of two SNPs (A896G and C1196T). Cases (
n
= 108) were obtained from a LD outbreak in The Netherlands in 1999. Controls were exposed at the same outbreak, did not develop pneumonia, and were either unmatched (
n
= 421) or matched (
n
= 89) to patients for age, sex, and geographic residence. Allele 896G was associated with LD susceptibility with a frequency of 6.5% in the combined control group (matched and unmatched) vs. 2.5% in patients [odds ratio (OR) of 0.36, 95% confidence interval (C.I.) 0.14–0.91,
P
= 0.025]. In the matched control group comparison, allele 896G also showed a protective association with an OR of 0.27 (95% C.I. 0.09–0.75,
P
= 0.008). An analysis of genotype frequencies (896 AA vs. AG and GG) demonstrated similar protective associations (patient vs. combined control group comparison, OR = 0.35, 95% C.I. 0.14–0.89,
P
= 0.02; matched control group comparison, OR = 0.25, 95% C.I. 0.09–0.71,
P
= 0.006). Allele 1196T cosegregated with allele 896G and, thus, had identical associations. Although previous studies suggest that these TLR4 SNPs are associated with an increased risk of infection, this study demonstrates an association with resistance. This protective association illustrates that an innate immune receptor can mediate either beneficial or deleterious inflammatory responses and that these outcomes vary with different pathogens.
Correction of factor IX deficiency in mice by embryonic stem cells differentiated
in vitro
Authors: Fair Jeffrey H. , Cairns Bruce A. , LaPaglia Michael A. , Caballero Montserrat , Pleasant W. Andrew , Hatada Seigo , Kim Hyung-suk , Gui Tong , Pevny Larysa , Meyer Anthony A. , Stafford Darrel W. , Smithies Oliver , Frelinger Jeffrey A.
Published: February 2005

Murine embryonic stem (ES) cells are pluripotent, but significant functional engraftment does not occur when they are introduced into the liver. However, here we demonstrate that functional liver engraftment does occur if the ES cells (from strain 129 mice) are first differentiated
in vitro
for 7 days in the presence of FGF. Strikingly, when these differentiated cells, termed putative endodermal precursors (PEPs), were injected into their livers, two of six C57BL/6 and four of eight BALB/c factor IX (F-IX)-deficient mice survived for >7 days, even though the recipients were of a different strain and, in the case of the BALB/c recipients, had a complete MHC mismatch. F-IX was detected in all six of the PEP-injected survivors. Two mice subsequently died of causes unrelated to F-IX; the others survived until death at 38 or 115 days after the transplantation. No uninjected control F-IX-deficient mice survived for >7 days. Large confluent regions of sinusoidal PEP engraftment were demonstrated by immunofluorescence in the long-term BALB/c survivors. The PEP engraftment was not associated with detectable cell fusion, and the transplantation was accompanied with only a low incidence of teratoma formation.
Rapid nitric oxide-mediated S-nitrosylation of estrogen receptor: Regulation of estrogen-dependent gene transcription
Authors: Garbán Hermes J. , Márquez-Garbán Diana C. , Pietras Richard J. , Ignarro Louis J.
Published: February 2005

Nitric oxide (NO) and estrogen receptor (ER) are both important mediators of signal transduction in cardiovascular and reproductive tissues. In this study, we evaluated NO-mediated S-nitrosylation of ER and assessed the effect of this structural modification on transcription-related functions of ER. We have found selective inhibitory effects of NO on specific binding of ER to specific estrogen-responsive elements (ERE) that can be reversed in the presence of the reducing agent, DTT, thus suggesting that S-nitrosylation of thiolate–zinc centers may occur within the ER molecule. Furthermore, we examined inhibitory effects of NO on ER-dependent transcriptional activity by using an ERE-driven reporter gene system. By monitoring biophysical changes in the structure of NO-treated or untreated human recombinant ERα,we obtained evidence for the formation of
S
-nitrosothiols in the ER molecule. In addition, we have detected specific S-nitrosylation of cysteine residues within the ER molecule by immunodetection of
S
-nitrosocysteine moieties in ER. Collectively, these findings suggest an important physiological role for NO in modification of human ER structure by S-nitrosylation, an effect that leads, in turn, to impaired DNA-binding activity of ER and subsequent blockade of estrogen-dependent gene transcription. Thus, NO-induced S-nitrosylation of ER can occur at cysteine residues that coordinate Zn
2+
within the two major DNA-binding Zn-finger domains of ER, resulting in selective inhibition of DNA-binding at specific ERE. This cross-communication between NO and ER may favor activation of rapid (nongenomic) signaling pathways and subsequent modulation of downstream genomic activity.
Artemis-independent functions of DNA-dependent protein kinase in Ig heavy chain class switch recombination and development
Authors: Rooney Sean , Alt Frederick W. , Sekiguchi JoAnn , Manis John P.
Published: February 2005

Assembly of Ig genes in B lineage cells involves two distinct DNA rearrangements. In early B cell development, site-specific double strand breaks (DSBs) at germ-line V, D, and J gene segments are joined via nonhomologous end-joining (NHEJ) to form variable region exons. Activated mature B cells can change expressed Ig heavy chain constant region exons by class switch recombination (CSR), which also involves DSB intermediates. Absence of any known NHEJ factor severely impairs joining of cleaved V, D, and J segments. In NHEJ, DNA-dependent protein kinase (DNA-PK), which is comprised of the Ku70/80 end-binding heterodimer and the catalytic subunit (DNA-PKcs), activates Artemis to generate a nuclease that processes DSBs before ligation. Because inactivation of DNA-PKcs components also severely affects CSR, we tested whether DNA-PK also functions in CSR via activation of Artemis. To obviate the requirement for V(D)J recombination, we generated DNA-PKcs- and Artemis-deficient B cells that harbored preassembled Ig heavy chain and κ-light chain “knock-in” (HL) alleles. We found that Artemis-deficient HL B cells undergo robust CSR, indicating that DNA-PKcs functions in CSR via an Artemis-independent mechanism. To further elucidate potential Artemis-independent functions of DNA-PKcs, we asked whether the embryonic lethality associated with double-deficiency for DNA-PKcs and the related ataxia-telangiectasia-mutated (ATM) kinase was also observed in mice doubly deficient for ATM and Artemis. We found that ATM/Artemis double-deficient mice were viable and born in normal Mendelian numbers. Therefore, we conclude that DNA-PKcs has Artemis-independent functions in CSR and normal development.
Estrogen contributes to the onset, persistence, and malignant progression of cervical cancer in a human papillomavirus-transgenic mouse model
Authors: Brake Tiffany , Lambert Paul F.
Published: February 2005

Cervical cancer is a leading cause of death by cancer among women worldwide. High-risk human papillomaviruses (HPVs) are the major etiological agents for cervical cancer, but other factors likely contribute to cervical cancer, because these cancers commonly arise decades after initial exposure to HPV. Estrogen is thought to be one such cofactor; however, its temporal requirements in human cervical cancer are not known. Here we evaluate the temporal requirements of estrogen in cervical carcinogenesis in a mouse model for HPV-associated cervical cancer. Tumors arising in HPV16 transgenic mice treated with estrogen for 9 months were greatly increased in their size compared with tumors developing after 6 months of estrogen treatment. HPV16 transgenic mice treated 6 months with estrogen followed by 3 months without exogenous estrogen had significantly fewer tumors and the tumors were smaller and less aggressive than those arising in mice treated the full 9 months. Importantly, cervical cancers that arose in the mice treated the first 6 of 9 months with estrogen must have regressed, based upon the reduced incidence of cancers in these mice compared with those treated for 6 months with estrogen, then immediately analyzed. We conclude that estrogen plays a critical role not only in the genesis of cervical cancer but also in its persistence and continued development in this mouse model. These findings raise the clinically relevant possibility that, if human cervical cancer has a similar dependence on estrogen for continued tumor growth, then antiestrogen therapy may be effective in the treatment of cervical cancer.
Diabetes and hypertension increases in a society with abdominal obesity: results of the Mexican National Health Survey 2000
Authors: Sánchez-Castillo Claudia P , Velásquez-Monroy Oscar , Lara-Esqueda Agustín , Berber Arturo , Sepulveda Jaime , Tapia-Conyer Roberto , James W Philip T
Published: February 2005

Objectives

To determine the prevalences of overweight, obesity, type 2 diabetes mellitus (DM) and hypertension (HT) in the Mexican population and compare them with those of a previous Mexican urban survey and an American survey.

Design

A structured, randomised, nationally representative Mexican sample was compared with a 1993 Mexican urban survey and the US Third National Health and Nutrition Examination Survey (NHANES III) of non-Hispanic Whites.

Setting

The Mexican National Health Survey 2000.

Subjects

Subjects were 12856 men and 28332 women, aged 20–69 years, who had their body weight, height, waist circumference (WC), blood pressure and fasting capillary blood glucose measured.

Results

Mexican adult men and women had a high prevalence of overweight (41.3 and 36.3%, respectively) and obesity (19.4 and 29.0%, respectively), similar to those in the USA in 1988–1992 and exceeding those of the 1993 Mexican survey. The prevalence of HT was 33.3% in men and 25.6% in women, with inferred DM rates of 5.6 and 9.7%, respectively. Abdominal obesity affected 46.3% of men (WC ≥ 94 cm) and 81.4% of women (WC ≥ 80 cm). There was a high prevalence of abdominal obesity in normal-weight women, with co-morbidities relating better to WC than to body mass index (BMI) in both sexes. Rates of DM and HT exceeded US rates on a comparable BMI or WC basis in adults aged <50 years.

Conclusion

The high prevalence of obesity and abdominal obesity in Mexicans is associated with markedly increased prevalences of DM and HT to levels comparable with, or even higher than, those in NHANES III of non-Hispanic Whites.
Protection, promotion and support of breast-feeding in Europe: current situation
Authors: Cattaneo Adriano , Yngve Agneta , Koletzko Berthold , Guzman Luis Ruiz
Published: February 2005

Objective

To describe the current situation regarding protection, promotion and support of breast-feeding in Europe, as a first step towards the development of a blueprint for action.

Design and setting

A questionnaire was completed by 29 key informants and 128 other informants in the EU, including member states, accession and candidate countries.

Results

EU countries do not fully comply with the policies and recommendations of the Global Strategy on Infant and Young Child Feeding that they endorsed during the 55th World Health Assembly in 2002. Some countries do not even comply with the targets of the Innocenti Declaration (1990). Pre-service training on breast-feeding practice is inadequate and in-service training achieves only low to medium coverage. The Baby Friendly Hospital Initiative is well developed only in three countries; in 19 countries, less than 15% of births occur in baby-friendly hospitals. The International Code of Marketing of Breastmilk Substitutes, endorsed in 1981 by all countries, is not fully applied and submitted to independent monitoring. The legislation for working mothers meets on average the International Labour Organization standards, but covers only women with full formal employment. Voluntary mother-to-mother support groups and trained peer counsellors are present in 27 and 13 countries, respectively. Breast-feeding rates span over a wide range; comparisons are difficult due to use of non-standard methods. The rate of exclusive breast-feeding at 6 months is low everywhere, even in countries with high initiation rates.

Conclusions

EU countries need to revise their policies and practices to meet the principles inscribed in the Global Strategy on Infant and Young Child Feeding in order to better protect, promote and support breast-feeding.
Vitamin A deficiency and child mortality in Mozambique
Authors: Aguayo Victor M , Kahn Sonia , Ismael Carina , Meershoek Stephan
Published: February 2005

Background

In areas where vitamin A deficiency (VAD) is prevalent, vitamin A repletion reduces child mortality by 23% on average.

Objectives

To estimate the potential child survival benefits of policies and programmes aimed at controlling VAD in Mozambique, and to make policy and programme recommendations.

Methods

The potential contribution of VAD to child mortality in Mozambique was estimated by combining the observed VAD prevalence in the under-5s (71.2%), the measured child mortality effects of VAD (risk of death in children with VAD = 1.75 times higher than in children without VAD) and the observed under-5 mortality rate in the country (210 per 1000 live births).

Results

In Mozambique, an estimated 2.3 million children below the age of 5 years are vitamin-A-deficient. In the absence of appropriate policy and programme action, VAD will be the attributable cause of over 30 000 deaths annually in the under-5s. This represents 34.8% of all-cause mortality in this age group.

Discussion

Vitamin A supplementation (VAS) has been adopted as a short- to medium-term strategy to control VAD in children, and is integrated into routine child health services. However, the last VAS coverage survey showed that only 46% of children received a vitamin A supplement in the 6 months preceding the survey. If VAS coverage is to increase significantly in the foreseeable future, four areas appear to be of paramount importance: (1) reduce missed opportunities for VAS such as visits of sick children to child health services and community outreach activities; (2) take advantage of all potential opportunities for accelerating VAS coverage, such as additional vaccination campaigns and emergency response activities; (3) strengthen health workers’ training, supervision and monitoring skills; and (4) increase community demand for VAS of children. Biannual VAS, as the primary component of an integrated strategy for VAD control in children, has the promise to be among the most cost-effective/high-impact child survival interventions in Mozambique.
The effect of drug abuse on body mass index in Hispanics with and without HIV infection
Authors: Forrester Janet E , Tucker Katherine L , Gorbach Sherwood L
Published: February 2005

Objective

There is a widely held view that the lower weight of drug abusers is attributable to diet. However, many studies on the dietary intake of drug abusers have failed to find energy insufficiency, while non-dietary factors have rarely been examined. The purpose of this study was to examine non-dietary factors that could affect the weight of drug abusers with and without HIV infection.

Design

Participants were recruited into one of three groups: HIV-positive drug abusers (n=85), HIV-negative drug abusers (n=102) and HIV-positive persons who do not use drugs (‘non-drug abusers’, n=98). Non-dietary factors influencing weight included infection with HIV and/or hepatitis, malabsorption, resting energy expenditure and physical activity.

Setting

The baseline data from a prospective cohort study of the role of drug abuse in HIV/AIDS weight loss conducted in Boston, USA.

Subjects

The first 286 participants to enrol in the study.

Results

HIV-positive drug abusers had a body mass index (BMI) that was significantly lower than that of HIV-positive non-drug abusers. The differences in weight were principally differences in fat. In the men, cocaine abuse, either alone or mixed with opiates, was associated with lower BMI, while strict opiate abuse was not. Infection with HIV or hepatitis, intestinal malabsorption, resting energy expenditure and physical activity, as measured in this study, did not explain the observed differences in weight and BMI.

Conclusions

Drug abuse, and especially cocaine abuse, was associated with lower weight in men. However, infection with HIV and/or hepatitis, malabsorption and resting energy expenditure do not explain these findings.
Development and validation of a food-frequency questionnaire for the determination of detailed fatty acid intakes
Authors: Cantwell Marie M , Gibney Michael J , Cronin Denis , Younger Kate M , O'Neill John P , Hogan Linda , Flynn Mary AT
Published: February 2005

Objective

To validate a fat intake questionnaire (FIQ) developed to assess habitual dietary intake while focusing on the assessment of detailed fatty acid intake including total trans unsaturated fatty acids (TUFA).

Design

An 88 food item/food group FIQ was developed using a meal pattern technique. Validation was achieved by comparison with dietary intake assessed by a modified diet history (DH) in a cross-over design. Eighty-four individuals supplied adipose tissue biopsies for linoleic acid and total TUFA analysis as an independent validation of the FIQ and DH.

Setting

Medical Centre, Dublin Airport, Republic of Ireland.

Subjects

One hundred and five healthy volunteers (43 females and 62 males aged 23–63 years).

Results

Significant correlations (P < 0.0005) were achieved for intakes of energy (0.78), total fat (0.77), saturated fat (0.77), monounsaturated fat (0.63), polyunsaturated fat (0.73), TUFA (0.67) and linoleic acid (0.71) assessed by the FIQ compared with the DH. Linoleic acid intake assessed by the FIQ and the DH was significantly correlated with adipose tissue concentrations (r = 0.58 and 0.49, respectively; P<0.005); however, total TUFA intake was poorly correlated with adipose tissue concentrations (r = 0.17 and 0.10 for FIQ and DH, respectively).

Conclusions

The FIQ compared favourably with the DH in assessing habitual diet, in particular fatty acid intake. In addition, the FIQ was successfully validated against the linoleic acid composition of adipose tissue, an independent biomarker of relative fatty acid status. The FIQ could therefore be used as an alternative to the DH as it is a shorter, less labour-intensive method.
The Swedish Demand—Control—Support Questionnaire (DCSQ): Factor structure, item analyses, and internal consistency in a large population
Authors: Sanne Bjarte , Torp Steffen , Mykletun Arnstein , Dahl Alv A.
Published: February 2005

Aim: This paper examined the psychometric properties of the Swedish Demand—Control—Support Questionnaire (DCSQ), which is a shorter and modified version of Karasek's Job Content Questionnaire (JCQ). Methods: The study encompassed 5,227 workers born in 1953—57 from the population-based Hordaland Health Study. DCSQ, a 17-item questionnaire, covers psychological demands, decision latitude, and social support in the workplace. The workers were manually classified according to the Standard Classification of Occupations. The main statistical methods were principal component analyses, and estimation of internal consistency and the subscales' shared variance by Cronbach's coefficient α and Pearson's correlation coefficients, respectively. Results: The study gave support to the tri-dimensional factor structure of DCSQ. Decision latitude tended to split into skill discretion and decision authority in skill-level homogeneous samples. The specificity of the item loadings was satisfactory except for ``conflicting demands''. The inter-correlation of the three main subscales was weak. The internal consistency of the subscales was generally satisfactory. Conclusions: The psychometric properties of DCSQ are satisfactory. Being shorter and easier to use than the more comprehensive JCQ, DCSQ represents an important alternative, particularly if respondent burden and data-collection costs need to be minimized.
Live imaging of wound inflammation in Drosophila embryos reveals key roles for small GTPases during in vivo cell migration
Authors: Stramer Brian , Wood Will , Galko Michael J. , Redd Michael J. , Jacinto Antonio , Parkhurst Susan M. , Martin Paul
Published: February 2005

Aa robust inflammatory response to tissue damage and infection is conserved across almost all animal phyla. Neutrophils and macrophages, or their equivalents, are drawn to the wound site where they engulf cell and matrix debris and release signals that direct components of the repair process. This orchestrated cell migration is clinically important, and yet, to date, leukocyte chemotaxis has largely been studied in vitro. Here, we describe a genetically tractable in vivo wound model of inflammation in the Drosophila melanogaster embryo that is amenable to cinemicroscopy. For the first time, we are able to examine the roles of Rho-family small GTPases during inflammation in vivo and show that Rac-mediated lamellae are essential for hemocyte motility and Rho signaling is necessary for cells to retract from sites of matrix– and cell–cell contacts. Cdc42 is necessary for maintaining cellular polarity and yet, despite in vitro evidence, is dispensable for sensing and crawling toward wound cues.
Protein synthesis persists during necrotic cell death
Authors: Saelens Xavier , Festjens Nele , Parthoens Eef , Vanoverberghe Isabel , Kalai Michael , van Kuppeveld Frank , Vandenabeele Peter
Published: February 2005

Cell death is an intrinsic part of metazoan development and mammalian immune regulation. Whereas the molecular events orchestrating apoptosis have been characterized extensively, little is known about the biochemistry of necrotic cell death. Here, we show that, in contrast to apoptosis, the induction of necrosis does not lead to the shut down of protein synthesis. The rapid drop in protein synthesis observed in apoptosis correlates with caspase-dependent breakdown of eukaryotic translation initiation factor (eIF) 4G, activation of the double-stranded RNA-activated protein kinase PKR, and phosphorylation of its substrate eIF2-α. In necrosis induced by tumor necrosis factor, double-stranded RNA, or viral infection, de novo protein synthesis persists and 28S ribosomal RNA fragmentation, eIF2-α phosphorylation, and proteolytic activation of PKR are absent. Collectively, these results show that, in contrast to apoptotic cells, necrotic dying cells retain the opportunity to synthesize proteins.
Structural determinants for EB1-mediated recruitment of APC and spectraplakins to the microtubule plus end
Authors: Slep Kevin C. , Rogers Stephen L. , Elliott Sarah L. , Ohkura Hiroyuki , Kolodziej Peter A. , Vale Ronald D.
Published: February 2005

EB1 is a member of a conserved protein family that localizes to growing microtubule plus ends. EB1 proteins also recruit cell polarity and signaling molecules to microtubule tips. However, the mechanism by which EB1 recognizes cargo is unknown. Here, we have defined a repeat sequence in adenomatous polyposis coli (APC) that binds to EB1's COOH-terminal domain and identified a similar sequence in members of the microtubule actin cross-linking factor (MACF) family of spectraplakins. We show that MACFs directly bind EB1 and exhibit EB1-dependent plus end tracking in vivo. To understand how EB1 recognizes APC and MACFs, we solved the crystal structure of the EB1 COOH-terminal domain. The structure reveals a novel homodimeric fold comprised of a coiled coil and four-helix bundle motif. Mutational analysis reveals that the cargo binding site for MACFs maps to a cluster of conserved residues at the junction between the coiled coil and four-helix bundle. These results provide a structural understanding of how EB1 binds two regulators of microtubule-based cell polarity.
Roles of discontinuities in bio-inspired adhesive pads
Authors: Chung Jun Young , Chaudhury Manoj K
Published: February 2005

Morphological intricacies of the biological attachment pads generate considerable interest owing to their remarkable ability to control adhesion to various surfaces. Motivated by the adhesive microstructures of insects, we examine the behaviour of adhesion and crack propagation in patterned adhesive films. These films are made of silicone elastomers that were patterned with lateral, longitudinal or crosswise incisions from which a thin silanized glass plate was removed in a displacement-controlled peel experiment. The behaviours of crack propagation on these patterned adhesive films are controlled by simple incision patterns, their depths and spacing. With the crosswise incisions, significant enhancement (×10–20) of fracture energy has been achieved. These findings point towards an important mechanism by which of biological organisms might enhance adhesion, and provide a simple design principle for manipulating the interfacial fracture in a variety of artificial attachment devices.
Mentoring Students in Higher Education
Authors: Jowett Val , Stead Richard
Published: February 2005

Outlines the particular interest of Leeds Metropolitan University, in
mentoring for students and young professionals. Based on a project by
LMU, and sponsored by the Department of Employment, seeks to further the
debate about how effective mentoring relationships can be established
within the context of work‐based learning, paying particular attention
to the issue of training mentors.
Evaluating Mentoring
Authors: Gibb Stephen
Published: February 2005

Discusses the process of evaluating mentoring and suggests that, with
mentoring for young people, this includes evaluating mentoring outcomes,
the contribution of mentoring to the broader initiatives of which it is
normally a part, and identifying the costs of mentoring schemes. Gives
frameworks for considering these areas of evaluation in more detail.
Points out that effective evaluation of all these areas depends on the
use of a number of different methods, including interviews, surveys and
case studies. In conclusion, highlights some move critical issues about
determining the overall value of mentoring for young people.
Jaguar uses X350 car to pioneer use of self‐piercing rivets
Authors: Mortimer John
Published: February 2005

Jaguar Cars, the luxury UK automaker, is developing a new car, the X350. For the first time, the company is to use aluminium body panels for the body shell. Aluminium can be difficult to weld so self‐piercing rivets are used for metal joining. The rivets are used in place of spot welding, but are applied by rivet setters attached to robots.
Implementation of a robotic depalletizing cell
Authors: Burgess Glen
Published: February 2005

This case study describes the application of robots to an agricultural depalletizing operation. Discusses the reasons for adopting robotics, the requirements of the application and the resulting system performance.
Hungry for success – future directions in gastrobotics research
Authors: Wilkinson Stuart
Published: February 2005

The paper discusses the new emerging technology of “gastrobotics”, or food‐powered mobile robots. The concept of self‐sufficiency is examined, and it is postulated that robots with stomachs offer the promise of sustained autonomous operation in an unstructured outdoor environment, which is not possible with existing alternative methods. Data is presented that compares the energy density of various foods, with that of common chemical batteries and gasoline. The various food groups are discussed as regards their suitability as fuel for gastrobots, and a variety of potential applications are presented. The basic operation of a microbial fuel cell is described in its role as an artificial stomach, thereby demonstrating how this biotechnology can efficiently convert food into electricity.
Arithmetic robot modules control robotic production
Authors: Hollingum Jack
Published: February 2005

Discusses the forthcoming installation of an ABB Flexible Automation
beam preparation system at an offshore platform construction company in
Scotland. Using a six‐axis robot suspended from a boom, the system
will be able to cut beams to any length with any desired end profile using an
Arithmetic Robot Application Control [ARAC] system, which allows
virtually any beam profile to be programmed into the system, in seconds by
means of ARAC macros. Prior to cutting, the robot will exchange its gas torch
for a 3‐D probe to measure the actual beam dimensions and compare
these with the stored data design. Describes how the ARAC software package
works and gives examples of other applications such as the cutting of round
tubes for structural assemblies, multi‐pass welding and
tube‐to‐sheet welding.
Task planning in robot simulation
Authors: Owens John
Published: February 2005

Describes the approach adapted by Robot Simulations Ltd in their development of successive versions of the Workspace software package, namely to place the emphasis on using the knowledge of the geometry of the parts and machines in a production cell to automate those aspects of the traditional design method that can be performed by the computer. Also describes how some of the task planning tools embedded within robot simulation can work and what they can deliver in terms of shortening the design time of a production cell and improving the speed and quality of the production process.
Advanced robotics – thought for food
Authors: Kochan Anna
Published: February 2005

Reports on the industrial robots papers presented at the two‐day International Workshop on Advanced Robotics and Intelligent Machines held at the University of Salford. Subjects included: development of robotics in the UK; work on a generalized framework for intelligent robotic systems to analyse the solution of a co‐operative foraging problem; research on developing a Cartesian simulator for rational agents; a neuro‐force controller for robotic contact with non‐rigid environments; development of a new control system architecture; and an intelligent robot equipped with multiple sensors enabling response to a disordered environment.
Stäubli path optimization
Authors: Kochan Anna
Published: February 2005

Summarizes the main characteristics of Stäubli’s V_Trajsig software option which the company claims provides a unique way of achieving an optimum path‐following performance.
A 3D finite element formulation describing the frictional behavior of rubber on ice and concrete surfaces
Authors: Huemer T. , Liu W.N. , Eberhardsteiner J. , Mang H.A.
Published: February 2005

The frictional behavior of rubber materials on various contact surfaces is strongly affected by the contact pressure and the relative sliding velocity as well as the environmental temperature. Based on a great number of experiments of rubber blocks moving on concrete and ice surfaces, a friction law for 3D contact analyses is presented in this paper. It is characterized by the dependency on the contact pressure, sliding velocity and the environmental temperature. The identification and correction of the parameters of this friction law were done by means of a least‐square method followed by re‐analyses of the respective experiments. Several examples are given in a numerical investigation of the frictional behavior of rubber materials.
Computational modelling of viscoplastic fluids based on a stabilised finite element method
Authors: Peric D. , Slijepcevic S.
Published: February 2005

This work is concerned with computational modelling of viscoplastic fluids. The flows considered are assumed to be incompressible, while the viscoplastic laws are obtained by incorporating a yield stress below which the fluid is assumed to remain non‐deformable. The Bingham fluid is chosen as a model problem and is considered in detail in the text. The finite element formulation adopted in this work is based on a version of the stabilised finite element method, known as the Galerkin/least‐squares method, originally developed by Hughes and co‐workers. This methodology allows use of low and equal order interpolation of the pressure and velocity fields, thus providing an efficient finite element framework. The Newton‐Raphson method has been chosen for solution of the incremental non‐linear problem arising through the temporal discretisation of the evolution problem. Numerical examples are provided to illustrate the main features of the described methodology.
Boolean Algebra from the Lattice Point of View
Authors: Lee Edward T.
Published: February 2005

Using lattices, presents Boolean Algebra, which is usually introduced using its postulate‐oriented approach. Relationships among sets, relations, lattices and Boolean algebra are shown to form a distributive but not complemented lattice. Provides examples together with corresponding Hasse diagrams. References useful application areas.
Wiener’s Insight into Communication
Authors: von Glasersfeld Ernst
Published: February 2005

Briefly describes the impact that Wiener’s work had on language and communication. He believed that a message was “a sequence of measurable events distributed in time” – a signal that could only be interpreted by a receiver who was in possession of the particular code. This went against the traditional beliefs of semantics that meaning travelled in a communication channel. Bemoans the fact that Wiener’s insights on this subject did not become established but hopes one day that they might.
Norbert Wiener and the Social Sciences
Authors: Geyer Felix , van der Zouwen Johannes
Published: February 2005

Aims to analyse the influence of Norbert Wiener’s ideas on the social sciences and on social systems, including society as a whole. Describes Wiener’s own attitudes regarding the applicability of cybernetics to social systems and his vision on the development of modern society. Highlights sociologists and political scientists who were inspired by his ideas and deals with researchers who tried to apply his ideas to social systems. Concludes by evaluating to what extent specific ideas of Wiener have impacted on the social sciences.
Bionics: psychocybernetics of the human memory –
Part II: modelling of the human instantaneous memory
Authors: Mrchev Simeon J.
Published: February 2005

Presents research on human memory modelling. Gives a description of the memory process (as a whole) in its functional details by means of adding, processing and synthesizing psychological data using the creation of a model base. Compares the created psychological equivalent to the adequate mathematical‐algorithmic multi‐apparatus descriptions. Presents the programme‐developed human memory model as a precondition for microelectronic realizations (robot technique, computers and other bionic‐cybernetical systems).
Optimal environmental policy under imperfect information
Authors: Papakyriazis Artemis , Papakyriazis Panagiotis
Published: February 2005

The purpose of this paper is to examine the role of information structure in the design of the structure and parameters of an optimal regulatory mechanism. In particular, the paper analyzes both firm and public agency behavior under environmental externality internalization schemes and stochastic externality measurements of emissions and concentrations. It is shown that in general, the optimal environmental control policy involves the derivation of regulatory controls, measurement controls and the sequential estimation of inaccessible emissions and concentrations by a Kalman filter.
Some complementary concepts of communication theory
Authors: Skyttner Lars
Published: February 2005

To enhance the generality and usefulness of classic communication theory, some complementary concepts and ideas have been introduced and commented against the background of General Living Systems Theory (GLS). The paper begins with an extended definition of the problem of communication and continues with a presentation of the concept of natural channels. Basic ideas like the interrelation between time, place, and channel with its four different categories of communication are presented. Also main qualities of a message like informability, detectability, and localizability are analysed. Finally some general ideas regarding coding and transmission of messages are presented. The paper ends with the conclusion that classic communication theory still is highly relevant with no serious anomalies threatening its existence. This truth is confirmed by the fact that the complementary concepts presented here fit well into its existing framework.
The in’s and out’s of library budget preparation
Authors: Evans G. Edward
Published: February 2005

Newcomers to the budget process seldom realize that it is much more than just one element (most often an annual activity) in the management cycle. Those individuals who succeed in securing the funds requested are those who understand it is a complex‐year‐round process. They also recognize the fact that it is a political process as well as competitive in nature. This article explores some of the most important issues to think about, if one wants to improve one’s chances of succeeding in the “budget battle”. Topics covered are who should be involved, environmental factors, the budget cycle, defending the request, the political issues, budget formats and end‐user involvement.
Getting started with library digitization projects: funding your first (and subsequent) digital projects
Authors: Eden Brad
Published: February 2005

The digitization of our unique resources, and digital projects that exhibit and display these resources, have taken on a new importance in the electronic environment. Finding funds and support for these endeavors, however, requires skills and talents that often have to be developed individually. Yet, there are many funding sources for digitization and digital projects, and the rewards and monies are there for those who enter this arena. This article will examine how to prepare for, apply for funds and grants, and begin your first digitization project, as well as how to approach continued funding of digital projects.
Study on emergency response preparedness of hazardous materials transportation
Authors: Aini M.S. , Fakhru’l‐Razi A. , Daud M. , Ibrahim W.M.N. , Tangavelu S.K.
Published: February 2005

Notes the recent increase in interstate shipments of hazardous materials, by road, in Malaysia following rapid expansion in the manufacturing sector. Although there has been no major accident involving transportation of hazardous materials, the high rate of road accidents has raised great concerns concerning motor vehicles carrying hazardous goods and petroleum products. Determines the emergency preparedness and response plans of the transportation companies. Data were obtained from management and drivers, and the results revealed that the companies did not have a proper management system of safe transportation, had inadequate training of personnel, and the transport vehicles were not provided with appropriate tools and equipment for emergency response during mishaps. The drivers lacked general awareness and principal knowledge of hazardous material emergency response. Suggests that there is an urgent need to stipulate legal requirements for hazardous material transportation in Malaysia.
Organizational and employee interests in programs of work based learning
Authors: Costley Carol
Published: February 2005

Work based programs of study are being constructed between universities and organizations, increasingly in the UK. This article explores some of the tensions between the organization and individual employees in gaining benefit from the programs. The article draws on evidence from individual employees and managers of two university centers that run work based programs. Individual employees were found to gain considerable benefit from the programs although there were sometimes tensions about the nature of their studies. Organizations gained short‐term benefits and it was suggested that greater benefit could be gained if they managed the knowledge in their organizations more effectively.