bluuebunny/crossref_metadata_2025 huggingface dataset:
All-transretinoic acid modulates radiation-induced proliferation of lung fibroblasts via IL-6/IL-6R system
Authors: Tabata Chiharu , Kubo Hajime , Tabata Rie , Wada Manabu , Sakuma Keiichiro , Ichikawa Masataka , Fujita Shiro , Mio Tadashi , Mishima Michiaki
Published: October 2005

Although high-dose thoracic radiotherapy is an effective strategy for some malignancies including lung cancers and malignant lymphomas, it often causes complications of radiation fibrosis. To study the mechanism initiating tissue fibrosis, we investigated irradiation-induced cytokine production from human lung fibroblastic cells and found that IL-6 production was stimulated by irradiation. IL-6 is an autocrine growth factor for human myeloma cells, and retinoic acid is reported to inhibit their growth. Thus we evaluated the effect of all- trans retinoic acid (ATRA) on cell proliferation of lung fibroblasts along with the cytokine/receptor system. Irradiation-dependent stimulation of IL-6 production was correlated with increased NF-κB activity, and ATRA reduced this effect. Irradiation also increased the levels of mRNA for IL-6R and gp130, which were blocked by coexisting ATRA. Furthermore, IL-6 stimulated cell proliferation in dose-dependent manner but was overcome by pharmacological concentration of ATRA. These effects of ATRA were inhibited by rottlerin, which suggests ATRA abolished irradiation-induced stimulation through a PKCδ-dependent pathway. Finally, we demonstrated that IL-6 transcripts in the lung were upregulated at 2 mo after irradiation, and the effect was inhibited by the intraperitoneal administration of ATRA. ATRA is expected to have an advantage for radiotherapy in its antitumor effects, as reported previously, and to prevent radiotherapy-induced pulmonary injury.
Early Event-related Potential Effects of Syllabic Processing during Visual Word Recognition
Authors: Carreiras Manuel , Vergara Marta , Barber Horacio
Published: October 2005

A number of behavioral studies have suggested that syllables might play an important role in visual word recognition in some languages. We report two event-related potential (ERP) experiments using a new paradigm showing that syllabic units modulate early ERP components. In Experiment 1, words and pseudowords were presented visually and colored so that there was a match or a mismatch between the syllable boundaries and the color boundaries. The results showed color-syllable congruency effects in the time window of the P200. Lexicality modulated the N400 amplitude, but no effects of this variable were obtained at the P200 window. In Experiment 2, high-and low-frequency words and pseudowords were presented in the congruent and incongruent conditions. The results again showed congruency effects at the P200 for low-frequency words and pseudowords, but not for high-frequency words. Lexicality and lexical frequency effects showed up at the N400 component. The results suggest a dissociation between syllabic and lexical effects with important consequences for models of visual word recognition.
Analysis of Single-Unit Responses to Emotional Scenes in Human Ventromedial Prefrontal Cortex
Authors: Kawasaki Hiroto , Adolphs Ralph , Oya Hiroyuki , Kovach Christopher , Damasio Hanna , Kaufman Olaf , Howard Matthew
Published: October 2005

Lesion and functional imaging studies in humans have shown that the ventral and medial prefrontal cortex is critically involved in the processing of emotional stimuli, but both of these methods have limited spatiotemporal resolution. Conversely, neurophysiological studies of emotion in nonhuman primates typically rely on stimuli that do not require elaborate cognitive processing. To begin bridging this gap, we recorded from a total of 267 neurons in the left and right orbital and anterior cingulate cortices of four patients who had chronically implanted depth electrodes for monitoring epilepsy. Peristimulus activity was recorded to standardized, complex visual scenes depicting neutral, pleasant, or aversive content. Recording locations were verified with postoperative magnetic resonance imaging. Using a conservative, multistep statistical evaluation, we found significant responses in 56 neurons; 16 of these were selective for only one emotion class, most often aversive. The findings suggest sparse and widely distributed processing of emotional value in the prefrontal cortex, with a predominance of responses to aversive stimuli.
fMRI Reveals a Common Neural Substrate of Illusory and Real Contours in V1 after Perceptual Learning
Authors: Maertens Marianne , Pollmann Stefan
Published: October 2005

Perceptual learning involves the specific and relatively permanent modification of perception following a sensory experience. In psychophysical experiments, the specificity of the learning effects to the trained stimulus attributes (e.g., visual field position or stimulus orientation) is often attributed to assumed neural modifications at an early cortical site within the visual processing hierarchy. We directly investigated a neural correlate of perceptual learning in the primary visual cortex using fMRI. Twenty volunteers practiced a curvature discrimination on Kanizsa-type illusory contours in the MR scanner. Practice-induced changes in the BOLD response to illusory contours were compared between the pretraining and the posttraining block in those areas of the primary visual cortex (V1) that, in the same session, had been identified to represent real contours at corresponding visual field locations. A retinotopically specific BOLD signal increase to illusory contours was observed as a consequence of the training, possibly signaling the formation of a contour representation, which is necessary for performing the curvature discrimination. The effects of perceptual training were maintained over a period of about 10 months, and they were specific to the trained visual field position. The behavioral specificity of the learning effects supports an involvement of V1 in perceptual learning, and not in unspecific attentional effects.
Animal-Assisted Prolonged Exposure: A Treatment for Survivors of Sexual Assault Suffering Posttraumatic Stress Disorder
Authors: Bleiberg James , Prout Maurice , Debiak Dennis , Lefkowitz Carin , Paharia Indira
Published: November 2005

This paper proposes the development of a new model of treatment for survivors of sexual abuse suffering from Posttraumatic Stress Disorder (PTSD). Foa, Rothbaum, Riggs, and Murdock (1991) and Foa, Rothbaum, and Furr (2003) support Prolonged Exposure (PE) as a highly effective treatment for PTSD. However, PE can be intimidating to survivors, contributing to hesitancy to participate in the treatment. This paper posits that animal-assisted therapy (AAT) will decrease anxiety, lower physiological arousal, enhance the therapeutic alliance, and promote social lubrication. The paper also posits that AAT will enhance the value of PE by making it more accessible to survivors, increasing social interaction, and perhaps decreasing the number of sessions required for habituation to the traumatic memories.
The Song of Moses: a basis for Isaiah's prophecy
Authors: Keiser Thomas A.
Published: November 2005

Similarities between II Isaiah and Deuteronomy xxxii are commonly noted, however, little work has been done regarding the nature of that relationship. This article argues that there is a direct and conscious literary, theological and thematic dependence between these texts. Theologically, both passages proclaim the incomparability of Yahweh in the context of judgment-deliverance intervention with respect to Israel with the basis for the switch from judgment to deliverance the same in both texts. Thematic similarities are evident in a common presentation of the Lord, and with similar motifs such as remembrance, creation, witness, etc. Direct literary dependence is evident in the utilization of uncommon words and expressions, some of which occur in similar contexts.
Xerxes und (k)eine Marduk-Statue Überlegungen zu einem Randthema alttestamentlicher Prophetenexegese
Authors: Höffken Peter
Published: November 2005

Until now the story about Xerxes, carrying off a statue of Marduk from Babylon, is used in OT scholarship (U. Berges; M. Kessler e.a.). Herodot, however, is silent about that theme. He speaks about a statue, which is not Marduk. Also the archaeological findings are not clear in speaking about such an catastrophe of Esangila. We should therefore not use the Xerxes-story in OT scholarship in the future.
The call for revenge in Jeremiah's complaints (Jer xi-xx)
Authors: Avioz Michael
Published: November 2005

This article deals with the troublesome issue of Jeremiah's calls for revenge in the so-called 'Jeremiah's laments' (Jer xi-xx). Such calls are strange due to the fact Israelite prophets are usually conceived as intercessors. After surveying the different views and criticizing them, the author offers three solutions to the problem. Instead of focusing on our moral judgment of Jeremiah's calls for revenge, the author tries to show how they were interpreted by the author of the book of Jeremiah. Jeremiah's calls are designed according to the principle of measure for measure; the prophet is described as God's messenger who is worthy of being protected; and finally Jeremiah is conceived as trying to let justice be shown.
Ambivalent images of birth in Psalm vii 15
Authors: Grohmann Marianne
Published: November 2005

In this article Psalm vii 15 is analysed by means of close reading, interaction theories of metaphor and a reader-oriented approach, including Jewish medieval commentaries. The very fabric of Psalm vii 15 is made up of the tension between the constructive image of birth and the destructive aspects of the wicked. The verse does not correspond to the expectations of the reader: e.g. the sequence of stages in the birth process is unusual: labour—pregnancy—birth; the birth process is described with masculine verbs, and it is not clear who the subject is. Ps. vii 15 is an example of the fact that concrete and abstract features often go together in biblical metaphors. The presentation of the enemies' negative features in personified images of birth makes them more drastic. It reduces the possible connotations of birth to its negative aspects. Using birth as a negative image, the text shows something of the ambivalence of birth.
Are Color Categories Innate or Internalized? Hypotheses and Implications
Authors: Bimler David
Published: November 2005

The considerable agreement across languages in the way they categorize the color domain, despite independent historical development, demands an explanation. One option is to postulate a universal innate representation of the color categories, 'hardwired' into each observer's brain. An alternative is that observers internalize their color categories through a process of cultural (linguistic) transmission, constrained by some kind of 'optimality hypothesis' to account for the cross-language agreement. A number of optimality hypotheses are reviewed. It is tempting to believe that the vivid experiential quality of the categories can only be explained if they are determined by innate representations rather than by linguistic imprinting. However, linguistic transmission of color categories – perturbed from their optimal boundaries by special circumstances – fits best with the experience of dichromats. Even for the 'primary hue' categories, where the case for innate representations should be strongest, the evidence is far from convincing.
Color, Color Terms, Categorization, Cognition, Culture: An Afterword
Authors: Dedrick Don
Published: November 2005

Recent work on color naming challenges the idea that there are shared perceptually salient colors or color categories that are "hardwired" into homo sapiens and provide the basis for one of the most famous cross-cultural claims of all time, Brent Berlin and Paul Kay's claim that there is a small number of "basic" color terms (eleven), and that some subset of these terms is present in every human language (Berlin & Kay, 1969; see Kay and Maffi, 1999; Kay and Reiger, 2003; and Kay 2005 for updates).
Praying for a Good Spirit: Text, Context and Meaning of Luke 11.13
Authors: North J. Lionel
Published: November 2005

The meaning of 'Good Spirit', whether as part of Luke's autograph (it is the reading that some churches regarded as original and therefore was the one requiring interpretation) or as part of the apparatuscriticus, lies in the context of the two passages in LXX where 'Good Spirit' was already found, associated with Prayer, Torah and Way (2 Esdr. 19.20 [Neh. 9.20]; Ps. 142.10 [143.10]). Its meaning there was reactivated either by the evangelist or by an interpreter familiar with LXX. Egyptian, Zoroastrian and Neronian contexts may also be relevant.
Circuits of Power in Practice: Strategic Ambiguity as Delegation of Authority
Authors: Davenport Sally , Leitch Shirley
Published: November 2005

Most power relationships between organizations and stakeholders are episodic circuits of power whereby resource dependence is exacerbated by prohibitive rules. Such relationships are usually constraining rather than empowering and generate resistance and reluctant compliance rather than co-operation and creativity. Clegg's (1989) concept of facilitative circuits of power, however, suggests that some power relationships, particular where high amounts of discretion are delegated, can result in innovation by stakeholders. Public sector agencies have multiple and diverse external stakeholder groups that they need to influence in order to implement their strategies. In this paper, we explore a facilitative circuit of power using a case study of a public sector research funding organization that employed strategic ambiguity to delegate considerable authority to stakeholders, stimulating a variety of creative responses during a period of major system restructuring. Risks associated with such a practice include the generation of active and passive resistance as well as a propensity for the system to revert to an episodic power circuit over time. Despite these risks, we propose that the deployment of strategic ambiguity is a previously unrecognized mode of high discretionary strategic agency in authority delegation that can generate creative responses on the part of stakeholders within a facilitative circuit of power.
The Mystical Marriage of the Blessed Henry Suso
Authors: Wackernagel Wolfgang
Published: November 2005

Mystical marriage - or hierogamy - is without a doubt a significant aspect of the theme of the androgyne in medieval literature. In this paper we consider these themes, taking as a guide the last eight chapters of the Life by Henry Suso (1295-1366). Introduced by an epigraph in Latin: Sicut aquila (Like an eagle), these eight chapters are a literary work in their own right, which can therefore be labelled Sicut aquila. Indeed this is no longer an autobiographical narrative by the Servant of the Eternal Wisdom, but a romantic metaphysical flight written in the form of a lovers’ dialogue between Suso - sometimes called Frater Amandus - and his beloved spiritual daughter.
The ‘Third Gender’ of the Inuit
Authors: d'Anglure Bernard Saladin
Published: November 2005

At a time when western societies seem to have lost their markers, once found in sexual life, in gender relationships, in the sexual division of tasks, in standard definitions of the individual and the person, of family and kin, at a time, too, when they are bending under the weight of an exponential build-up of texts, theories and scientific discoveries, as ephemeral as they are brilliant, in the life sciences as well as in history, it is good to take time out to go and examine an indigenous society which, only fifty years ago, was still living from hunting, trapping, fishing and gathering. The people in this instance are the Inuit (as they name themselves, literally meaning: ‘the real humans’).
Economic analyses for ICT in elderly healthcare: questions and challenges
Authors: Vimarlund Vivian , Olve Nils-Göran
Published: November 2005

Elderly healthcare is a likely arena for extensive change in years to come, and information and communication technology (ICT) will be an important enabler of such change. Before investing in new systems and practices, there will be a call for evaluations. To date, economic evaluations of ICT applications in healthcare have been rare, and a literature review did not turn up any examples of such evaluations of elderly care. The options for elderly care will often have to transcend organization boundaries, as the point of many ICT initiatives now being discussed is to make healthcare institutions, home care, and self-administered care interact in new ways. Analysts performing evaluations of such complex changes will have to be very specific about such classic issues in economic analysis as defining alternatives, the basis for comparison, and combining different indicators into an overall evaluation.
The response of VEGF-stimulated endothelial cells to angiostatic molecules is substrate-dependent
Authors: Addison Christina L , Nör Jacques E , Zhao Huijun , Linn Stephanie A , Polverini Peter J , Delaney Christie E
Published: November 2005

Background

The microenvironment surrounding cells can exert multiple effects on their biological responses. In particular the extracellular matrix surrounding cells can profoundly influence their behavior. It has been shown that the extracellular matrix composition in tumors is vastly different than that found in normal tissue with increased amounts of certain matrices such as collagen I. It has been previously demonstrated that VEGF stimulation of endothelial cells growing on type I collagen results in the induction of bcl-2 expression and enhanced endothelial cell survival. We sought to investigate whether this increased endothelial cell survival resulted in the failure of angiostatic molecules to inhibit angiogenesis.

Results

We now demonstrate that VEGF-induced survival on collagen I impairs the ability of three known angiostatic molecules, TSP-1, IP-10 and endostatin to inhibit endothelial cell proliferation. Apoptosis of endothelial cells, growing on collagen I, induced by TSP-1 and IP-10 was also inhibited following VEGF stimulation. In contrast, endostatin induced apoptosis in these same cells. Further analysis determined that endostatin did not decrease the expression of bcl-2 nor did it increase activation of caspase-3 in the presence of VEGF. Alternatively, it appeared that in the presence of VEGF, endostatin induced the activation of caspase-8 in endothelial cells grown on collagen I. Furthermore, only endostatin had the ability to inhibit VEGF-induced sprout formation in collagen I gels.

Conclusion

These data suggest that TSP-1, IP-10 and endostatin inhibit endothelial cells via different mechanisms and that only endostatin is effective in inhibiting angiogenic activities in the presence of collagen I. Our results suggest that the efficacy of angiostatic treatments may be impaired depending on the context of the extracellular matrix within the tumor environment and thus could impede the efficacy of angiostatic therapies.
Analysis of four DLX homeobox genes in autistic probands
Authors: Hamilton Steven P , Woo Jonathan M , Carlson Elaine J , Ghanem Nöel , Ekker Marc , Rubenstein John LR
Published: November 2005

Background

Linkage studies in autism have identified susceptibility loci on chromosomes 2q and 7q, regions containing the DLX1/2 and DLX5/6 bigene clusters. The DLX genes encode homeodomain transcription factors that control craniofacial patterning and differentiation and survival of forebrain inhibitory neurons. We investigated the role that sequence variants in DLX genes play in autism by in-depth resequencing of these genes in 161 autism probands from the AGRE collection.

Results

Sequencing of exons, exon/intron boundaries and known enhancers of DLX1, 2, 5 and 6 identified several nonsynonymous variants in DLX2 and DLX5 and a variant in a DLX5/6intragenic enhancer. The nonsynonymous variants were detected in 4 of 95 families from which samples were sequenced. Two of these four SNPs were not observed in 378 undiagnosed samples from North American populations, while the remaining 2 were seen in one sample each.

Conclusion

Segregation of these variants in pedigrees did not generally support a contribution to autism susceptibility by these genes, although functional analyses may provide insight into the biological understanding of these important proteins.
Cerebrospinal fluid HIV infection and pleocytosis: Relation to systemic infection and antiretroviral treatment
Authors: Spudich Serena S , Nilsson Annelie C , Lollo Nicole D , Liegler Teri J , Petropoulos Christos J , Deeks Steven G , Paxinos Ellen E , Price Richard W
Published: November 2005

Background

Central nervous system (CNS) exposure to HIV is a universal facet of systemic infection. Because of its proximity to and shared barriers with the brain, cerebrospinal fluid (CSF) provides a useful window into and model of human CNS HIV infection.

Methods

Prospective study of the relationships of CSF to plasma HIV RNA, and the effects of: 1) progression of systemic infection, 2) CSF white blood cell (WBC) count, 3) antiretroviral therapy (ART), and 4) neurological performance. One hundred HIV-infected subjects were cross-sectionally studied, and 28 were followed longitudinally after initiating or changing ART.

Results

In cross-sectional analysis, HIV RNA levels were lower in CSF than plasma (median difference 1.30 log10 copies/mL). CSF HIV viral loads (VLs) correlated strongly with plasma VLs and CSF WBC counts. Higher CSF WBC counts associated with smaller differences between plasma and CSF HIV VL. CSF VL did not correlate with blood CD4 count, but CD4 counts <50 cells/μL associated with a low prevalence of CSF pleocytosis and large differences between plasma and CSF VL. CSF HIV RNA correlated neither with the severity of the AIDS dementia complex (ADC) nor abnormal quantitative neurological performance, although these measures were associated with depression of CD4 counts.

In subjects starting ART, those with lower CD4 counts had slower initial viral decay in CSF than in plasma. In all subjects, including five with persistent plasma viremia and four with new-onset ADC, CSF HIV eventually approached or reached the limit of viral detection and CSF pleocytosis resolved.

Conclusion

CSF HIV infection is common across the spectrum of infection and is directly related to CSF pleocytosis, though whether the latter is a response to or a contributing cause of CSF infection remains uncertain. Slowing in the rate of CSF response to ART compared to plasma as CD4 counts decline indicates a changing character of CSF infection with systemic immunological progression. Longer-term responses indicate that CSF infection generally responds well to ART, even in the face of systemic virological failure due to drug resistance. We present simple models to explain the differing relationships of CSF to plasma HIV in these settings.
Association of paternal age at birth and the risk of breast cancer in offspring: a case control study
Authors: Choi Ji-Yeob , Lee Kyoung-Mu , Park Sue Kyung , Noh Dong-Young , Ahn Sei-Hyun , Yoo Keun-Young , Kang Daehee
Published: November 2005

Background

Older paternal age may increase the germ cell mutation rate in the offspring. Maternal age may also mediate in utero exposure to pregnancy hormones in the offspring. To evaluate the association between paternal and maternal age at birth with the risk of breast cancer in female offspring, a case-control study was conducted in Korea.

Methods

Histologically confirmed breast cancer cases (n = 1,011) and controls (n = 1,011) with no present or previous history of cancer, matched on year of birth and menopausal status, were selected from several teaching hospitals and community in Seoul during 1995–2003. Information on paternal and maternal ages and other factors was collected by interviewed questionnaire. Odds ratio (OR) and 95% confidence interval (95% CI) were estimated by unconditional logistic regression model adjusting for family history of breast cancer in 1st or 2nd degree relatives, and lifetime estrogen exposure duration.

Results

The risk of breast cancer significantly increased as the paternal age increased (p for trend = 0.025). The association was stronger after controlling for maternal age; women whose fathers were aged ≥40 years at their birth had 1.6-fold increased risk of breast cancer compared with fathers aged <30 years. This association was profound in breast cancer cases in premenopausal women (OR = 1.9, 95% CI = 1.12–3.26, for paternal aged ≥40 vs. <30) (p for trend = 0.031). Although the risk of breast cancer increased as maternal age increased up to the intermediate, and then reduced; the risks in women whose mother were aged 25–29, 30–34, and ≥35 yrs at birth compared to women whose mothers were aged <25 years, were 1.2, 1.4, and 0.8, respectively, the trend was not significant (p for trend = 0.998).

Conclusion

These findings suggest that older paternal age increases the risk of breast cancer in their female offspring.
Back pain reporting in young girls appears to be puberty-related
Authors: Wedderkopp Niels , Bo Andersen Lars , Froberg Karsten , Leboeuf-Yde Charlotte
Published: November 2005

Background

There is a large increase in back pain reporting in the early teens. In no previous study has the prevalence of low back pain been investigated in relation to the onset of puberty. The objective of this study was to establish whether the onset of puberty is associated with back pain reporting in young girls.

Methods

A subsample of 254 girls aged 8–10 years and 165 girls aged 14–16 years from a cross-sectional survey of 481 children aged 8–10 years and 325 adolescents aged 14–16 years of both sexes.

Main outcome measures were back pain defined as low back pain, mid back pain, and/or neck pain in the past month.

Other variables of interest were Puberty (five different stages), age, body mass index, and smoking. Independent information on onset of puberty was obtained through a physical examination and on back pain through an individual structured interview. The association was studied between onset of puberty and the outcome variable (the one month period prevalence of back pain), controlling for overweight, and smoking. Odds ratios with 95% confidence intervals were used to describe bivariate associations, logistic regression with robust standard errors was used for multivariate analyses.

Results

There is a highly significant trend for increased back pain reporting with increasing level of puberty until maturity is reached. The biggest leap appears between the second level (beginning of puberty) and the third level (mid puberty) and the findings remain after controlling for the covariates. These results emanate from the low back, whereas pain in the mid back and neck do not seem to be linked with pubertal stage.

Conclusion

In girls, the reporting of low back pain increases in frequency during puberty until maturity, regardless of age. Why some girls are susceptible to back pain in the early stage of puberty is unknown.
Association between lifestyle factors and plasma adiponectin levels in Japanese men
Authors: Tsukinoki Rumi , Morimoto Kanehisa , Nakayama Kunio
Published: November 2005

Background

Adiponectin is an adipocyte-specific protein that plays a role in obesity, insulin resistant, lipid metabolism, and anti-inflammation. Hypoadiponectinemia may be associated with a higher risk for type 2 diabetes and cardiovascular disease. Some studies suggest that adiponectin levels are modulated by lifestyle factors, but little is known about the associations between lifestyle factors and plasma adiponectin levels in Japanese people. We therefore investigated the associations between lifestyle factors and plasma adiponectin levels in general Japanese men.

Methods

The subjects were 202 Japanese male workers who participated in an annual health check. They provided details about anthropometrical data, blood collection, their use of prescribed medication, and the clinical history of their families. They also completed a self-administered questionnaire about their lifestyles.

Results

Subjects with plasma adiponectin levels below 4.0 μg/ml had significantly lower levels of HDL cholesterol and higher levels of BMI, SBP, DBP, total cholesterol, FBG, and platelets than did subjects with higher adiponectin levels. In multiple logistic regression after multiple adjustment, a plasma adiponectin level below 4.0 μg/ml was significantly associated with smoking (odds ratio [OR] = 2.08, 95% confidence interval [CI] = 1.01–4.30), a daily diet rich in deep-yellow vegetables (OR = 0.25, 95% CI= 0.07–0.91), frequent eating out (OR = 2.45, 95% CI = 1.19–5.08), and physical exercise two or more times a week (OR = 0.21, 95% CI = 0.06–0.74).

Conclusion

Our findings show that adiponectin levels in general Japanese men are independently related to smoking, dietary factors, and physical exercise. We think that lifestyle habits might independently modulate adiponectin levels and that adiponectin might be the useful biomarker helping people to avoid developing type 2 diabetes and cardiovascular disease by modifying their lifestyles.
Processing sites in the human immunodeficiency virus type 1 (HIV-1) Gag-Pro-Pol precursor are cleaved by the viral protease at different rates
Authors: Pettit Steve C , Lindquist Jeffrey N , Kaplan Andrew H , Swanstrom Ronald
Published: November 2005

We have examined the kinetics of processing of the HIV-1 Gag-Pro-Pol precursor in an in vitro assay with mature protease added in trans. The processing sites were cleaved at different rates to produce distinct intermediates. The initial cleavage occurred at the p2/NC site. Intermediate cleavages occurred at similar rates at the MA/CA and RT/IN sites, and to a lesser extent at sites upstream of RT. Late cleavages occurred at the sites flanking the protease (PR) domain, suggesting sequestering of these sites. We observed paired intermediates indicative of half- cleavage of RT/RH site, suggesting that the RT domain in Gag-Pro-Pol was in a dimeric form under these assay conditions. These results clarify our understanding of the processing kinetics of the Gag-Pro-Pol precursor and suggest regulated cleavage. Our results further suggest that early dimerization of the PR and RT domains may serve as a regulatory element to influence the kinetics of processing within the Pol domain.
Allelic imbalances of chromosomes 8p and 18q and their roles in distant relapse of early stage, node-negative breast cancer
Authors: Morikawa Aki , Williams Tanisha Y , Dirix Luc , Colpaert Cecile , Goodman Michael , Lyles Robert H , Zhong Diansheng , Zhou Wei
Published: November 2005

Introduction

Identification of breast cancer patients at risk for postoperative distant relapse is an important clinical issue. Existing pathological markers can predict disease recurrence only to a certain extent, and there is a need for more accurate predictors.

Methods

Using 'counting alleles', a novel experimental method, we determined allelic status of chromosomes 8p and 18q in a case-control study with 65 early stage, node negative, invasive ductal carcinomas (IDCs). The association between allelic imbalance (AI) of both chromosomal markers and distant relapses was examined.

Results

Eighty percent of tumors contained 8pAI and sixty-eight percent of tumors contained 18qAI. However, none of the tumor samples retained both chromosome 8p and 18q alleles. More importantly, tumors with 8pAI but not 18qAI were more likely to have distant relapse compared to tumors with 18qAI but not 8pAI.

Conclusion

Our finding suggests that differential allelic loss of chromosomes 8p and 18q may represent subtypes of early stage IDC with different tumor progression behaviors.
Disability and health-related quality of life in Guillain-Barré syndrome during the first two years after onset: a prospective study
Authors: Forsberg Anette , Press Rayomand , Einarsson Ulrika , de Pedro-Cuesta Jésus , Holmqvist Lotta Widén
Published: October 2005

Objective: To describe changes in disability and health-related quality of life in patients with Guillain-Barré syndrome in Sweden during the first two years after onset.

Subjects: Forty-four patients were recruited from eight different hospitals, and 42 of them (mean age 52 years) were followed for two years. Evaluations were performed, primarily as home visits, at two weeks, two months, six months, one year and two years after onset.

Main measures: Disability was measured using the Katz Personal and Extended Activities of Daily Living Indexes, the Barthel Index, the Frenchay Activity Index and assessments of work capacity; health-related quality of life using the Sickness Impact Profile.

Results: At two weeks, one year and two years after onset of Guillain-Barrésyndrome, 76%, 14% and 12% of patients were dependent in personal activities of daily life (ADL); and 98%, 28% and 26% were dependent in instrumental ADL. At two weeks, all of the patients that were working before onset were unable to work owing to Guillain-Barré syndrome; at two years, 17% were unable to work. At two weeks, scores on Sickness Impact Profile were elevated in all dimensions; at two years, they remained elevated in the physical dimension and in the categories home management, work and recreation and pastimes.

Conclusions: The impact of Guillain-Barré syndrome on ADL, work, social activities and health-related quality is considerable two years after onset and presumably persists beyond this time point.
Effects of home exercises on motor performance in patients with Parkinson's disease
Authors: Caglar A T , Gurses H N , Mutluay F K , Kiziltan G
Published: October 2005

Objective: To investigate the effect of home exercises on the motor performance of patients with Parkinson's disease.

Design: A prospective blinded study with allocation of patients into their groups by alternate weeks.

Setting: A University Hospital neurology and physiotherapy department.

Subjects: Recruited from a movement disorders outpatient clinic of Cerrahpasa School of Medicine diagnosed with Parkinson's disease, classified as Hoehn and Yahr Grades I, II and III.

Interventions: Patients who fulfilled the inclusion criteria were recruited to the study. Each patient was evaluated at the end of first and second month after the baseline evaluation. Patients were divided into two groups. Those in the first and third week were put in the exercise group and second and fourth week in the control group. Patients in the exercise group (n=15) were given a schedule of exercises to undertake at home; the others (n=15) did not receive this instruction.

Measures: Ten- and 20-m walking test, first pace length, pace number in 10 m, walking around a chair, Nine Hole Peg Board (NHPB) test.

Results: Following the home exercise programme, patients in the exercise group showed improvement in walking 10 and 20 m, time elapsed to complete walking around a chair and length of the first pace length, and in the motor performance of both hands (p < 0.001).

Conclusions: A home-based rehabilitation programme for patients with Parkinson's disease helped to improve motor performance compared to patients who did not take advantage of a regular, professionally designed exercise programme.
GIS-based landslide hazard assessment: an overview
Authors: Huabin Wang , Gangjun Liu , Weiya Xu , Gonghui Wang
Published: October 2005

In recent years, landslide hazard assessment has played an important role in developing land utilization regulations aimed at minimizing the loss of lives and damage to property. A variety of approaches has been used in landslide assessment and these can be classified into qualitative factor overlay, statistical models, geotechnical process models, etc. However, there is little work on the satisfactory integration of these models with geographic information systems (GIS) to support slope management and landslide hazard mitigation. This paper deals with several aspects of landslide hazard assessment by presenting a focused review of GIS-based landslide hazard assessment: it starts with a framework for GIS-based assessment of landslide hazard; continues with a critical review of the state of the art in using GIS and digital elevation models (DEM) for mapping and modelling landslide hazards; and concludes with a description of an integrated system for effective landslide hazard assessment and zonation incorporating artificial intelligence and data mining technology in a GIS-based framework of knowledge discovery.
CD26+CD4+T cell counts and attack risk in interferon-treated multiple sclerosis
Authors: Sellebjerg F , Ross C , Koch-Henriksen N , Sørensen P Soelberg , Frederiksen J L , Bendtzen K , Sørensen T L
Published: October 2005

Biomarkers that allow the identification of patients with multiple sclerosis (MS) with an insufficient response to immunomodulatory treatment would be desirable, as currently available treatments are only incompletely efficacious. Previous studies have shown that the expression of CD25, CD26 and CCR5 on T cells is altered in patients with active MS. We studied the expression of these molecules by flow cytometry in patients followed for six months during immunomodulatory treatment. In interferon (IFN)-β-treated patients, we found that the hazard ratio for developing an attack was 2.8 in patients with CD26+CD4+T cell counts above median, and this risk was independent of the risk conferred by neutralizing anti-IFN-β antibodies. CD26+CD4+T cell counts may identify patients with MS at increased risk of attack during treatment with IFN-β.
Prognostic factors in multidisciplinary rehabilitation treatment in multiple sclerosis: an outcome study
Authors: Grasso M G , Troisi E , Rizzi F , Morelli D , Paolucci S
Published: October 2005

The aim of this outcome study was to evaluate the effectiveness and prognostic factors of inpatient multidisciplinary rehabilitation treatment in patients with multiple sclerosis (MS). We analysed 230 consecutive inpatients with MS admitted to an MS rehabilitation ward who followed an individualized, goal-oriented, multidisciplinary rehabilitation program. Every patient was submitted to a neurological examination and evaluated by means of Kurtzke’s Expanded Disability Status Scale (EDSS), with its functional systems (FS), Barthel Index (BI) and the Rivermead Mobility Index (RMI). We observed an effectiveness (percentage of potential improvement achieved during rehabilitation) of nearly 16% on BI and 8% on RMI, corresponding to an improvement in 124 patients (54%) on BI and 113 patients (49%) on RMI. Basal EDSS (β= -0.32, p<0.001), cognitive status (β= -0.15, p<0.05) and disease duration (β= -0.13, p<0.05) were negatively associated with effectiveness of treatment on BI (adjusted R2=0.176), whereas effectiveness on RMI was correlated only with the EDSS score (β=-0.34, p<0.001, adjusted R2=0.113). In the logistic regression analysis, the absence of severe sphincteric disturbances was correlated with the probability of improvement on BI that was nearly twice as high (OR=2.25, 95% CI 1.24-4.08) as that of other patients. Moreover, patients without severe cognitive deficits showed a similar probability (OR-2.37, 95% CI 1.05-5.33) of improvement on RMI. The results of this study provide further evidence that intensive multidisciplinary rehabilitation in MS is effective in the majority of MS patients and that early treatment may favour functional recovery.
Measuring quality of life in multiple sclerosis: not as simple as it sounds
Authors: Nicholl L , Hobart J C , Cramp A FL , Lowe-Strong A S
Published: October 2005

Data from a clinical study presented an opportunity to examine the psychometric properties of the Leeds Multiple Sclerosis Quality of Life scale (LMSQoL), which has undergone limited psychometric evaluation. LMSQoL and Multiple Sclerosis Quality of Life-54 (MSQoL-54) data were collected from 90 people with multiple sclerosis (MS) living in the community. Standard psychometric methods to examine data quality, scaling assumptions, scale to sample targeting, reliability, validity, and responsiveness were employed. The LMSQoL satisfied criteria for data quality (no missing data), scaling assumptions (item-total correlations: 0.24-0.56), reliability (Cronbach’s alpha: 0.71), and demonstrated responsiveness (effect size: 0.34). Correlations between the LMSQoL and MSQoL-54 physical (range:-0.02 to-0.50) and emotional subscales (range:-0.38 to-0.65) were similar; the magnitude and pattern was not consistent with predictions based on the construct purported to be measured by the LMSQoL. The LMSQoL satisfied many psychometric criteria in this small study, however, it was difficult to interpret the validity data. From this, two fundamental measurement issues are highlighted. Firstly, current methods of examining rating scales provide only circumstantial evidence of validity; secondly, health-rating scales should be developed on the basis of clear conceptual definitions.
An autopsied case of neuromyelitis optica with a large cavitary cerebral lesion
Authors: Nakamura M , Endo M , Murakami K , Konno H , Fujihara K , Itoyama Y
Published: October 2005

We report a case of neuromyelitis optica (NMO) with a large cerebral lesion. The patient had an episode of fever and consciousness disturbance with a tumefactive frontal white matter lesion at age 43, and then repeated bilateral optic neuritis and transverse myelitis until she died at age 63. Histopathological examinations revealed that marked tissue destruction, cavities and inflammatory changes typical of NMO were seen in the cerebrum as well as the optic nerves and spinal cord. This is the first autopsied case of NMO with a tumefactive cerebral lesion that later became cavitary.
Conservative bladder management in advanced multiple sclerosis
Authors: De Ridder D , Ost D , Van der Aa F , Stagnaro M , Beneton C , Gross-Paju K , Eelen P , Limbourg H , Harper M , Segal J C , Fowler C J , Nordenbo A
Published: October 2005

Anticholinergics and intermittent catheterization are the cornerstones of bladder management in early multiple sclerosis (MS). In advanced MS however, bladder management is based more on tradition than on evidence. Nurses seem to deal with catheter problems and chronic incontinence. Despite the abundant use of indwelling catheters, there is a lack for guidelines on catheter-induced problems. The psychosexual and social impact of bladder problems in advanced MS is often neglected. The international multidisciplinary special interest group on sexual, urological and bowel dysfunction in MS (SUBDIMS) as a special interest group of the Rehabilitation in Multiple Sclerosis (RIMS) was confronted with a high variability in practice and a lack of guidelines. A literature review was prepared during three multidisciplinary expert meetings. This review will be the basis of further initiatives to improve the urological treatment of patients with advanced MS.
Eph and NMDA receptors control Ca2+/calmodulin-dependent protein kinase II activation duringC. elegansoocyte meiotic maturation
Authors: Corrigan Chad , Subramanian Rajani , Miller Michael A.
Published: November 2005

Fertilization in the female reproductive tract depends on intercellular signaling mechanisms that coordinate sperm presence with oocyte meiotic progression. To achieve this coordination in Caenorhabditis elegans,sperm release an extracellular signal, the major sperm protein (MSP), to induce oocyte meiotic maturation and ovulation. MSP binds to multiple receptors, including the VAB-1 Eph receptor protein-tyrosine kinase on oocyte and ovarian sheath cell surfaces. Canonical VAB-1 ligands called ephrins negatively regulate oocyte maturation and MPK-1 mitogen-activated protein kinase (MAPK) activation. Here, we show that MSP and VAB-1 regulate the signaling properties of two Ca2+ channels that are encoded by the NMR-1 N-methyl D-aspartate type glutamate receptor subunit and ITR-1 inositol 1,4,5-triphosphate receptor. Ephrin/VAB-1 signaling acts upstream of ITR-1 to inhibit meiotic resumption, while NMR-1 prevents signaling by the UNC-43 Ca2+/calmodulin-dependent protein kinase II (CaMKII). MSP binding to VAB-1 stimulates NMR-1-dependent UNC-43 activation, and UNC-43 acts redundantly in oocytes to promote oocyte maturation and MAPK activation. Our results support a model in which VAB-1 switches from a negative regulator into a redundant positive regulator of oocyte maturation upon binding to MSP. NMR-1 mediates this switch by controlling UNC-43 CaMKII activation at the oocyte cortex.
Optimization of a piezoelectric bimorph grasper for use in minimally invasive surgical applications
Authors: Grujicic M , Zhao C L , Austin E M
Published: October 2005

The potential use of piezoelectric bimorph actuators in minimally invasive surgery suture-needle grasper/holder applications is explored computationally. Upon defining the design/functional requirements for such surgical tools, a finite element analysis of the underlying piezoelectric boundary value problem is combined with the genetic algorithm optimization routine to arrive at an optimal morphology of the suture-needle grasper/holder. The results obtained show that, if the actuator is based on several constant-thickness segments, a proper combination of thicknesses of such segments can substantially improve the performance of such surgical tools. Specifically, a good combination of the relatively large grasper-jaws opening and the required level of the holding force when the grasper is closed on a 0.5 mm diameter suture-needle is obtained. The effect of orientation of the poling direction in the piezoelectric layers on the performance of the bimorph actuator is also examined. It is found that, at the same level of the required grasping force, a change in the poling direction by about 2.3° from the through-the-thickness direction can increase the maximum grasper-jaws opening by about 10 per cent.
Comparative study of genetic algorithm and simulated annealing for optimal tolerance design formulated with discrete and continuous variables
Authors: Sing P K , Jain S C , Jain P K
Published: October 2005

Optimal tolerance design has been the focus of extensive research for a few decades. This has resulted in several formulations and solution algorithms for systematic tolerance design considering various aspects. Availability of different alternative manufacturing processes or machines for realization of a dimension is frequently encountered. In such cases optimal tolerance design must also consider optimal selection of a set of manufacturing processes or machines as appropriate. Such a non-linear multivariate optimal tolerance design problem results in a combinatorial and multi-modal solution space. Optimal solution of this advanced tolerance design problem is difficult using traditional optimization techniques. The problem formulation becomes more complex with simultaneous selection of design and manufacturing tolerances. The focus of the current research is on the optimal solution of this advanced and complex tolerance design problem. Genetic algorithm and simulated annealing as non-traditional global optimization techniques have been used to obtain the solution. Application of the solution techniques has been demonstrated with the help of appropriate examples. Comparison of the results establishes that the genetic algorithm is the superior of the two approaches.
Direct Synthesis of Spectrochemical Standards by Powder Metallurgy
Authors: Gerber W. O.
Published: November 2005

To by-pass the preliminary wet chemical analysis of standards, a procedure for mixing finely divided pure metal powders, briquetting under high pressure and either sintering or melting in a protecting atmosphere by high frequency electronic induction heating is discussed.