bluuebunny/crossref_metadata_2025 huggingface dataset:
Differential expression of RANK, RANK-L, and osteoprotegerin by synovial fluid neutrophils from patients with rheumatoid arthritis and by healthy human blood neutrophils
Authors: Poubelle Patrice E , Chakravarti Arpita , Fernandes Maria J , Doiron Karine , Marceau Andrée-Anne
Published: March 2007

Functional links between bone remodeling and the immune system in chronic inflammatory arthritis are mediated, in part, by the ligand of receptor activator of nuclear factor-kappa-B (RANK-L). Because neutrophils play a crucial role in chronic inflammation, the goal of this study was to determine whether proteins of the RANK/RANK-L pathway are expressed by synovial fluid (SF) neutrophils from patients with rheumatoid arthritis (RA) and to characterize this pathway in normal human blood neutrophils. The expression of RANK-L, osteoprotegerin (OPG), RANK, and tumor necrosis factor receptor-associated factor 6 (TRAF6) was determined by polymerase chain reaction, enzyme-linked immunosorbent assay, Western blotting, and cytofluorometry. RANK signaling was analyzed by the degradation of inhibitor of kappaB-alpha (I-κB-α). SF neutrophils from patients with RA express and release OPG and express the membrane-associated forms of RANK-L and RANK. In contrast, normal blood neutrophils express only the membrane-associated form of RANK-L. They do not express the mRNAs encoding OPG and RANK. SF neutrophils from RA patients and normal blood neutrophils release no soluble RANK-L. They express the mRNA for TRAF6. The expression of OPG and RANK by normal human blood neutrophils, however, can be induced by interleukin-4 + tumor necrosis factor-alpha and by SFs from patients with RA. In contrast, SFs from patients with osteoarthritis do not induce the expression of OPG and RANK. Moreover, the addition of RANK-L to normal blood neutrophils pretreated by SF from patients with RA decreased I-κB-α, indicating that RANK signaling by neutrophils stimulated with SF is associated with nuclear factor-kappa-B activation. In summary, RANK-L is expressed by inflammatory and normal neutrophils, unlike OPG and RANK, which are expressed only by neutrophils exposed to an inflammatory environment. Taken together, these results suggest that neutrophils may contribute to bone remodeling at inflammatory sites where they are present in significantly large numbers.
The association between patellar alignment on magnetic resonance imaging and radiographic manifestations of knee osteoarthritis
Authors: Kalichman Leonid , Zhang Yuqing , Niu Jingbo , Goggins Joyce , Gale Daniel , Zhu Yanyan , Felson David T , Hunter David J
Published: March 2007

The aim of our study was to evaluate the association between patellar alignment by using magnetic resonance imaging images and radiographic manifestations of patello-femoral osteoarthritis (OA). Subjects were recruited to participate in a natural history study of symptomatic knee OA. We examined the relation of patellar alignment in the sagittal plane (patellar length ratio (PLR)) and the transverse plane (sulcus angle (SA), lateral patellar tilt angle (LPTA), and bisect offset (BO)) to radiographic features of patello-femoral OA, namely joint space narrowing and patellar osteophytes, using a proportional odds logistic regression model while adjusting for age, sex, and bone mass index (BMI). The study sample consisted of 126 males (average age 68.0 years, BMI 31.2) and 87 females (average age 64.7 years, BMI 31.6), 75% of whom had tibiofemoral OA (a Kellgren-Lawrence score of 2 or more). PLR showed a statistically significant association with joint space narrowing and osteophytosis in the lateral compartment. SA showed significant association with medial joint space narrowing and with lateral and medial patellar osteophytosis. LPTA and BO showed significant association with both radiographic indices of the lateral compartment. Clear linear trends were found in association between PLR, LPTA and BO, and with outcomes associated with lateral patello-femoral OA. SA, LPTA, and BO showed linear trends of association with medial joint space narrowing. Results of our study clearly suggest the association between indices of patellar alignment and such features of patello-femoral OA as osteophytosis and joint space narrowing. Additional studies will be required to establish the normal and abnormal ranges of patellar alignment indices and their longitudinal relation to patello-femoral OA.
Association of estrogen receptor-α and progesterone receptor A expression with hormonal mammary carcinogenesis: role of the host microenvironment
Authors: Montero Girard Guadalupe , Vanzulli Silvia I , Cerliani Juan Pablo , Bottino María Cecilia , Bolado Julieta , Vela Jorge , Becu-Villalobos Damasia , Benavides Fernando , Gutkind Silvio , Patel Vyomesh , Molinolo Alfredo , Lanari Claudia
Published: March 2007

Introduction

Medroxyprogesterone acetate (MPA) induces estrogen receptor (ER)-positive and progesterone receptor (PR)-positive ductal invasive mammary carcinomas in BALB/c mice. We sought to reproduce this MPA cancer model in C57BL/6 mice because of their widespread use in genetic engineering. Within this experimental setting, we studied the carcinogenic effects of MPA, the morphologic changes in mammary glands that are induced by MPA and progesterone, and the levels of ER and PR expression in MPA-treated and progesterone-treated mammary glands. Finally, we evaluated whether the differences found between BALB/c and C57BL/6 mouse strains were due to intrinsic differences in epithelial cells.

Methods

The carcinogenic effect of MPA was evaluated in C57BL/6 mice using protocols proven to be carcinogenic in BALB/c mice. In addition, BALB/c and C57BL/6 females were treated with progesterone or MPA for 1 or 2 months, and mammary glands were excised for histologic studies and for immunohistochemical and Western blot evaluation of ER and PR. Hormone levels were determined by radioimmunoassay. Isolated mammary epithelial cells were transplanted into cleared fat pads of 21-day-old female Swiss nu/nu mice or control congenic animals.

Results

MPA failed to induce mammary carcinomas or significant morphologic changes in the mammary glands of C57BL/6 mice. The expression of ER-α and PR isoform A in virgin mice was surprisingly much higher in BALB/c than in C57BL/6 mammary glands, and both receptors were downregulated in progestin-treated BALB/c mice (P < 0.05). PR isoform B levels were low in virgin control mice and increased after progestin treatment in both strains. ER-β expression followed a similar trend. No differences in hormone levels were found between strains. Surprisingly, the transplantation of the epithelial mammary gland cells of both strains into the cleared fat pads of Swiss (nu/nu) mice abolished the mammary gland morphologic differences and the ER and PR differences between strains.

Conclusion

C57BL/6 mammary glands are resistant to MPA-induced carcinogenesis and to hormone action. MPA and progesterone have different effects on mammary glands. Low ER-α and PR-A levels in untreated mammary glands may be associated with a low-risk breast cancer profile. Although we cannot at this time rule out the participation of other, untested factors, our findings implicate the stroma as playing a crucial role in the strain-specific differential hormone receptor expression and hormone responsiveness.
Case mix, outcome, and activity for admissions to UK critical care units with severe acute pancreatitis: a secondary analysis of the ICNARC Case Mix Programme Database
Authors: Harrison David A , D'Amico Giovanna , Singer Mervyn
Published: March 2007

Introduction

Severe acute pancreatitis (SAP) requiring admission to a critical care unit is associated with high mortality and long lengths of stay. We describe the case mix, outcome, and activity of admissions with SAP who were identified from a high-quality clinical database.

Methods

We conducted a secondary analysis of the ICNARC (Intensive Care National Audit & Research Centre) Case Mix Programme Database of 219,468 admissions to 159 adult, general critical care units in England, Wales, and Northern Ireland for the period of 1995 to 2003 to identify admissions with SAP. The ability of the modified Glasgow criteria to discriminate hospital survivors from non-survivors was compared to that of the Acute Physiology and Chronic Health Evaluation (APACHE) II score and a number of individual physiological parameters.

Results

A total of 2,677 admissions with SAP were identified (1.2% of all admissions). Mortality for these admissions was 31% in the critical care unit and 42% in hospital. The median length of stay in the critical care unit was 3.8 days and was similar for survivors and non-survivors. Increasing numbers of modified Glasgow criteria were associated with increasing hospital mortality, but better discrimination was provided by the APACHE II score and by several physiological parameters.

Conclusion

SAP requiring critical care is associated with high mortality and long length of stay. The modified Glasgow criteria represent a simple measure of severity but were not designed to predict hospital mortality. It may be possible to develop a specific model for risk prediction in patients with SAP requiring critical care.
Alternative ion channel splicing in mesial temporal lobe epilepsy and Alzheimer's disease
Authors: Heinzen Erin L , Yoon Woohyun , Weale Michael E , Sen Arjune , Wood Nicholas W , Burke James R , Welsh-Bohmer Kathleen A , Hulette Christine M , Sisodiya Sanjay M , Goldstein David B
Published: March 2007

Background

Alternative gene transcript splicing permits a single gene to produce multiple proteins with varied functions. Bioinformatic investigations have identified numerous splice variants, but whether these transcripts are translated to functional proteins and the physiological significance of these alternative proteins are largely unknown. Through direct identification of splice variants associated with disease states, we can begin to address these questions and to elucidate their roles in disease predisposition and pathophysiology. This work specifically sought to identify disease-associated alternative splicing patterns in ion channel genes by comprehensively screening affected brain tissue collected from patients with mesial temporal lobe epilepsy and Alzheimer's disease. New technology permitting the screening of alternative splice variants in microarray format was employed. Real time quantitative PCR was used to verify observed splice variant patterns.

Results

This work shows for the first time that two common neurological conditions are associated with extensive changes in gene splicing, with 25% and 12% of the genes considered having significant changes in splicing patterns associated with mesial temporal lobe epilepsy and Alzheimer's disease, respectively. Furthermore, these changes were found to exhibit unique and consistent patterns within the disease groups.

Conclusion

This work has identified a set of disease-associated, alternatively spliced gene products that represent high priorities for detailed functional investigations into how these changes impact the pathophysiology of mesial temporal lobe epilepsy and Alzheimer's disease.
Correlation between near-surface electromagnetic soil parameters and early-time GPR signals: An experimental study
Authors: Pettinelli Elena , Vannaroni Giuliano , Di Pasquo Barbara , Mattei Elisabetta , Di Matteo Andrea , De Santis Alberto , Annan Peter A.
Published: March 2007

We explore a new approach to evaluate the effect of soil electromagnetic parameters on early-time ground-penetrating radar (GPR) signals. The analysis is performed in a time interval which contains the direct airwaves and ground waves, propagating between transmitting and receiving antennas. To perform the measurements we have selected a natural test site characterized by very strong lateral gradient of the soil electrical properties. To evaluate the effect of the subsoil permittivity and conductivity on the radar response we compare the envelope amplitude of the GPR signals received in the first [Formula: see text] within [Formula: see text]-wide windows, with the electrical properties ([Formula: see text] and [Formula: see text]) determined using time-domain reflectometry (TDR). The results show that the constitutive soil parameters strongly influence early-time signals, suggesting a novel approach for estimating the spatial variability of water content with GPR.
Lateral Spread Hazard Mapping of the Northern Salt Lake Valley, Utah, for a M7.0 Scenario Earthquake
Authors: Olsen Michael J. , Bartlett Steven F. , Solomon Barry J.
Published: March 2007

This paper describes the methodology used to develop a lateral spread-displacement hazard map for northern Salt Lake Valley, Utah, using a scenario M7.0 earthquake occurring on the Salt Lake City segment of the Wasatch fault. The mapping effort is supported by a substantial amount of geotechnical, geologic, and topographic data compiled for the Salt Lake Valley, Utah. ArcGIS® routines created for the mapping project then input this information to perform site-specific lateral spread analyses using methods developed by Bartlett and Youd (1992) and Youd et. al. (2002) at individual borehole locations. The distributions of predicted lateral spread displacements from the boreholes located spatially within a geologic unit were subsequently used to map the hazard for that particular unit. The mapped displacement zones consist of low hazard (0–0.1 m), moderate hazard (0.1–0.3 m), high hazard (0.3–1.0 m), and very high hazard (>1.0 m). As expected, the produced map shows the highest hazard in the alluvial deposits at the center of the valley and in sandy deposits close to the fault. This mapping effort is currently being applied to the southern part of the Salt Lake Valley, Utah, and probabilistic maps are being developed for the entire valley.
Bridge Functionality Relationships for Improved Seismic Risk Assessment of Transportation Networks
Authors: Padgett Jamie E. , DesRoches Reginald
Published: March 2007

Relationships between bridge damage and the resulting loss of functionality of the bridge are critical to assessing the impact of an earthquake event on the performance of the transportation network. This study addresses this data need by use of a Web-based survey of central and southeastern U.S. Department of Transportation bridge inspectors and officials. Results of the 28 responses are analyzed and offer a link between various types of bridge component damage and the expected level of allowable traffic carrying capacity due to closure decisions and repair procedures. This data is utilized to assess the probability of meeting various damage states, expressed in terms of restoration of functionality, and subsequently facilitate the refinement of component limit-state capacities for analytical fragility curve development. The bridge functionality relationships and methodology outlined serve as the basis for refinement of critical tools in the seismic risk assessment framework and improved assessment of transportation network performance.
Measurement of Serum Free Cortisol Shows Discordant Responsivity to Stress and Dynamic Evaluation
Authors: Christ-Crain Mirjam , Jutla Sukhdeep , Widmer Isabelle , Couppis Orestes , König Caroline , Pargger Hans , Puder Jardena , Edwards Ray , Müller Beat , Grossman Ashley B.
Published: March 2007

Context: Routinely available assays of adrenal function measure serum total cortisol (TC) and not the biologically active free cortisol (FC). However, there are few data on FC levels during surgical stress and in response to standard pharmacological tests.

Objective: Our objective was to evaluate TC and FC levels in different states of physical stress.

Design and Setting: We conducted a prospective observational study in a university hospital.

Participants and Main Outcome Measures: We measured TC and FC levels in 64 patients: group A, 17 healthy controls without stress; group B, 23 medical patients with moderate stress; and group C, 24 surgical patients undergoing coronary bypass grafting. Cortisol levels in group C were measured basally and at several time points thereafter and were compared with responsivity to a pharmacological dose of ACTH. FC was measured using equilibrium dialysis.

Results: In group C patients after extubation, the relative increase above basal FC was higher than the increase in TC levels (399 ± 266 vs. 247 ± 132% of initial values, respectively; mean ± sd; P = 0.02) and then fell more markedly, FC levels falling to 67 ± 49% and TC levels to 79 ± 36% (P = 0.04). After ACTH stimulation, TC levels increased to 680 ± 168 nmol/liter, which was similar to the increase with major stress (811 ± 268 nmol/liter). In contrast, FC levels increased to 55 ± 16 nmol/liter after ACTH stimulation but significantly greater with surgical stress to 108 ± 56 nmol/liter (P < 0.001).

Conclusion: The more pronounced increase in FC seen during stress as compared with the ACTH test suggests that this test does not adequately anticipate the FC levels needed during severe stress.
Stress Responsiveness in Adult Life: Influence of Mother’s Diet in Late Pregnancy
Authors: Reynolds Rebecca M. , Godfrey Keith M. , Barker Mary , Osmond Clive , Phillips David I. W.
Published: March 2007

Context: Men and women whose mothers ate an unbalanced high-protein, low-carbohydrate diet in late pregnancy have raised blood pressure. We recently showed that they also have raised fasting plasma cortisol concentrations. Because raised fasting cortisol concentrations probably reflect a greater response to the stress of fasting and venesection, we suspected that this diet may have led to increased stress responsiveness in the adult offspring.

Objective: The aim was to determine whether an unbalanced high-protein diet during pregnancy is associated with increased cortisol secretion in response to psychological stress in the offspring.

Design and Participants: Salivary cortisol concentrations were measured during a modified Trier Social Stress Test in 70 men and women aged 36.3 yr whose mothers had taken part in a dietary intervention in which they were advised to eat 1 pound (0.45 kg) of red meat daily during pregnancy and to avoid carbohydrate-rich foods.

Results: The offspring of women who reported greater consumption of meat and fish in the second half of pregnancy had higher cortisol concentrations during the Trier Test. Compared with the offspring of mothers who had reported eating no more than 13 meat/fish portions per week, the average cortisol concentrations were raised by 22% (95% confidence interval, 13 to 71%) and 46% (5 to 103%) in the offspring of those eating 14–16 and at least 17 portions per week, respectively.

Conclusions: These findings provide the first human evidence that an unbalanced high protein maternal diet during late pregnancy leads to increased cortisol secretion in response to psychological stress in the offspring.
Ikaros Is Regulated through Multiple Histone Modifications and Deoxyribonucleic Acid Methylation in the Pituitary
Authors: Zhu Xuegong , Asa Sylvia L. , Ezzat Shereen
Published: March 2007

The transcription factor Ikaros (Ik) is at the center of a functionally diverse chromatin-remodeling network that is critical for the development and regulation of both the immune and endocrine systems. Dominant negative forms of Ik result in neoplastic growth in mouse genetic studies and have been identified in human tumors. Ik modulates chromatin accessibility through associations with members of the NURD complex including histone deacetylase complexes. We show here that Ik expression in mouse pituitary corticotroph cells is itself regulated through histone modifications as well as DNA methylation. Examination of primary human pituitary specimens also identified a correlation of loss of Ik expression with the presence of DNA methylation in the untranslated exon 1 CpG island. These findings have important implications for the understanding of Ikaros’ role in epigenetic functions and suggest a potential role for demethylating agents in the treatment of related disorders.
Phosphorylation of adducin by protein kinase Cδ promotes cell motility
Authors: Chen Chien-Lin , Hsieh Yeun-Ting , Chen Hong-Chen
Published: March 2007

Protein kinase Cδ (PKCδ) has been implicated to play a crucial role in cell proliferation, differentiation and apoptosis. In this study, we have investigated the role of PKCδ in cell motility using Madin-Darby canine kidney cells. Overexpression of PKCδ promoted membrane protrusions, concomitant with increased cell motility. By contrast, suppression of PKCδ expression by RNA interference inhibited cell motility. Moreover, a fraction of PKCδ was detected at the edge of membrane protrusions in which it colocalized with adducin, a membrane skeletal protein whose phosphorylation state is important for remodeling of the cortical actin cytoskeleton. Elevated expression of PKCδ correlated with increased phosphorylation of adducin at Ser726 in intact cells. In vitro, PKCδ, but not PKCα, directly phosphorylated the Ser726 of adducin. Finally, we demonstrated that overexpression of both adducin and PKCδ could generate a synergistic effect on promoting cell spreading and cell migration. Our results support a positive role for PKCδ in cell motility and strongly suggest a link between PKCδ activity, adducin phosphorylation and cell motility.
An unusual vulval lesion in an HIV-infected woman
Authors: Boothby Meg , Radcliffe Keith
Published: March 2007

This is the case of a black African woman who presented with three distinct episodes of herpes simplex virus (HSV) infection unresponsive to first-line therapy. Clinical and virological resistance to aciclovir therapy was demonstrated, and although the first two episodes manifested as the deep ulceration often associated with HIV/HSV coinfection, the third was an atypical hypertrophic lesion. This is despite her CD4 count being persistently above 300 and there being no previous diagnosis of AIDS.
Patterns of HIV and syphilis infection in Northern Thailand 1998-2001
Authors: Beyrer Chris , Kawichai Surinda , A Hyder Joseph , Borwornsin Sompoth , Srirak Namtip , Natpratan Chawalit , D Celentano David , Khamboonruang Chirasak
Published: March 2007

Northern Thailand has been the epicentre of a largely heterosexually transmitted HIV epidemic that has recently involved married women. In preparation for HIV-prevention trials, we investigated patterns of HIV and syphilis risk through annually measured HIV and syphilis prevalence among northern Thai, peri-urban, community-dwelling men (n = 2564) and women (n = 3907) aged 18-35 years between 1998 and 2001. Crude HIV and syphilis prevalence were 3.3% and 2.7% for men and 2.3% and 2.1 % for women, respectively. In logistic regression models of HIV and syphilis, compared with married men/women, widowers and widows were at increased risk (odds ratio; 95% confidence interval) of syphilis (7.86; 1.56-39.6 and 3.3; 1.14-9.61, respectively) and HIV (12.68; 3.23-49.8 and 41.3; 24.3-70.3, respectively). The oldest women were at lower risk of HIV (0.43; 0.22-0.85). For men and women, those with syphilis were approximately three times more likely to have HIV. These unique population data illustrate evolving sex parity of HIV burden in northern Thailand.
Efficacy of a dish detergent in reducing populations of STI organisms in inoculated female condoms
Authors: Joanis C , Lopez L M , Gomez K , Ramm K , Rottjakob D
Published: March 2007

We assessed the efficacy of dish detergent in removing Neisseria gonorrhoeae, HIV-1, herpes simplex virus type 2 and Chlamydia trachomatis organisms from the surface of inoculated female condoms. The reductions achieved in organism counts with dish detergent were compared with those for household bleach and water. New (out-of-package) and pre-washed/re-lubricated female condoms were used. Dish detergent was as efficacious as bleach in reducing organism counts from the surface of inoculated female condoms. Both bleach and dish detergent performed better than water, although >3 log10 reductions were achieved with water alone. There was little difference in organism reduction between new and pre-washed condoms. Furthermore, 30 seconds of mechanical agitation (washing) had minimal added impact on organism removal. Reduction in organism counts with water alone suggests that dilution effect may have been as important in organism removal as the microbicidal properties of the detergent.
Activation of Epidermal Growth Factor Receptor Inhibits KCNQ2/3 Current through Two Distinct Pathways: Membrane PtdIns(4,5)P2Hydrolysis and Channel Phosphorylation
Authors: Jia Qingzhong , Jia Zhanfeng , Zhao Zhiying , Liu Boyi , Liang Huiling , Zhang Hailin
Published: March 2007

KCNQ2/3 currents are the molecular basis of the neuronal M currents that play a critical role in neuron excitability. Many neurotransmitters modulate M/KCNQ currents through their G-protein-coupled receptors. Membrane PtdIns(4,5)P2hydrolysis and channel phosphorylation are two mechanisms that have been proposed for modulation of KCNQ2/3 currents. In this study, we studied regulation of KCNQ2/3 currents by the epidermal growth factor (EGF) receptor, a member of another family of membrane receptors, receptor tyrosine kinases. We demonstrate here that EGF induces biphasic inhibition of KCNQ2/3 currents in human embryonic kidney 293 cells and in rat superior cervical ganglia neurons, an initial fast inhibition and a later slow inhibition. Additional studies indicate that the early and late inhibitions resulted from PtdIns(4,5)P2hydrolysis and tyrosine phosphorylation, respectively. We further demonstrate that these two processes are mutually dependent. This study indicates that EGF is a potent modulator of M/KCNQ currents and provides a new dimension to the understanding of the modulation of these channels.
Neurovascular Coupling Is Not Mediated by Potassium Siphoning from Glial Cells
Authors: Metea Monica R. , Kofuji Paulo , Newman Eric A.
Published: March 2007

Neuronal activity evokes localized changes in blood flow, a response termed neurovascular coupling. One widely recognized hypothesis of neurovascular coupling holds that glial cell depolarization evoked by neuronal activity leads to the release of K+onto blood vessels (K+siphoning) and to vessel relaxation. We now present two direct tests of this glial cell-K+siphoning hypothesis of neurovascular coupling. Potassium efflux was evoked from glial cells in the rat retina by applying depolarizing current pulses to individual cells. Glial depolarizations as large as 100 mV produced no change in the diameter of adjacent arterioles. We also monitored light-evoked vascular responses in Kir4.1 knock-out mice, where functional Kir K+channels are absent from retinal glial cells. The magnitude of light-evoked vasodilations was identical in Kir4.1 knock-out and wild-type animals. Contrary to the hypothesis, the results demonstrate that glial K+siphoning in the retina does not contribute significantly to neurovascular coupling.
Statistical Properties of Pauses of the High-Frequency Discharge Neurons in the External Segment of the Globus Pallidus
Authors: Elias Shlomo , Joshua Mati , Goldberg Joshua A. , Heimer Gali , Arkadir David , Morris Genela , Bergman Hagai
Published: March 2007

The neurons of many basal ganglia nuclei, including the external and internal globus pallidus (GPe and GPi, respectively) and the substantia nigra pars reticulata (SNr) are characterized by their high-frequency (50–100 spikes/s) tonic discharge (HFD). However, the high firing rate of GPe neurons is interrupted by long pauses. We studied the extracellularly recorded spiking activity of 212 well-isolated HFD GPe and 52 GPi/SNr neurons from five monkeys during different states of behavioral activity. An algorithm that maximizes the surprise function was used to detect pauses and pauser cells (“pausers”). Only 6% of the GPi/SNr neurons versus as many as 56% of the GPe neurons were classified as pausers. The GPe average pause duration equals 0.62 s. The interpause intervals follow a Poissonian distribution with a frequency of 13 pauses/minute. No linear relationship was found between pause parameters (duration or frequency) and the firing rate of the cell. Pauses were preceded by various changes in firing rate but not dominantly by a decrease. The average amplitude and duration of the spike waveform was modulated only after the pause but not before it. Pauses of pairs of cells that were recorded simultaneously were not correlated. The probability of GPe cells to pause spontaneously was extremely variable among monkeys (30–90%) and inversely related to the degree of the monkey's motor activity. These findings suggest that spontaneous GPe pauses are related to low-arousal periods and are generated by a process that is independent of the discharge properties of the cells.
Transmission of Spike Trains at the Retinogeniculate Synapse
Authors: Sincich Lawrence C. , Adams Daniel L. , Economides John R. , Horton Jonathan C.
Published: March 2007

Retinal spikes impinging on relay neurons in the lateral geniculate nucleus (LGN) generate synaptic potentials, which sometimes produce spikes sent to visual cortex. We examined how signal transmission is regulated in the macaque LGN by recording the retinal input to a single LGN neuron while stimulating the receptive field center with a naturalistic luminance sequence. After extracting the EPSPs, which are often partially merged with spike waveforms, we found that >95% of spikes were associated with an EPSP from a single retinal ganglion cell. Each spike within a “burst” train was generated by an EPSP, indicating that LGN bursts are inherited from retinal bursts. LGN neurons rarely fired unless at least two EPSPs summated within 40 ms. This facilitation in EPSP efficacy was followed by depression. If a spike was generated by the first EPSP in a pair, it did not alter the efficacy of the second EPSP. Hence, the timing of EPSPs arising from the primary retinal driver governs synaptic efficacy and provides the basis for successful retinogeniculate transmission.
A Conditional Pan-NeuronalDrosophilaModel of Spinocerebellar Ataxia 7 with a Reversible Adult Phenotype Suitable for Identifying Modifier Genes
Authors: Latouche Morwena , Lasbleiz Christelle , Martin Elodie , Monnier Véronique , Debeir Thomas , Mouatt-Prigent Annick , Muriel Marie-Paule , Morel Lydie , Ruberg Merle , Brice Alexis , Stevanin Giovanni , Tricoire Hérvé
Published: March 2007

Spinocerebellar ataxia 7 (SCA7) is a neurodegenerative disease caused by a polyglutamine (polyQ) expansion in the ataxin 7 (ATXN7) protein, a member of a multiprotein complex involved in histone acetylation. We have created a conditionalDrosophilamodel of SCA7 in which expression of truncated ATXN7 (ATXN7T) with a pathogenic polyQ expansion is induced in neurons in adult flies. In this model, mutant ATXN7T accumulated in neuronal intranuclear inclusions containing ubiquitin, the 19S proteasome subunit, and HSP70 (heat shock protein 70), as in patients. Aggregation was accompanied by a decrease in locomotion and lifespan but limited neuronal death. Disaggregation of the inclusions, when expression of expanded ATXN7T was stopped, correlated with improved locomotor function and increased lifespan, suggesting that the pathology may respond to treatment. Lifespan was then used as a quantitative marker in a candidate gene approach to validate the interest of the model and to identify generic modulators of polyQ toxicity and specific modifiers of SCA7. Several molecular pathways identified in this focused screen (proteasome function, unfolded protein stress, caspase-dependent apoptosis, and histone acetylation) were further studied in primary neuronal cultures. Sodium butyrate, a histone deacetylase inhibitor, improved the survival time of the neurons. This model is therefore a powerful tool for studying SCA7 and for the development of potential therapies for polyQ diseases.
Field linguistics: a minor manual
Authors: Dixon R.M.W.
Published: March 2007

This manual provides basic information concerning linguistic fieldwork. What is it? Why do it? The ethics involved. How to choose a field language and a field location. How to go about it. What to get – a comprehensive reference grammar (written in terms of basic linguistic theory), a volume of texts, and a dictionary/thesaurus. What to do: insofar as possible, become a member of the community (for ‘immersion fieldwork’); analyse texts; only use elicitation at a late stage, within the language of study (not from a lingua franca). How to work with consultants (and some things which should be avoided). Writing up the grammar. There is a short final section concerning field methods courses in a university.
A separate and peculiar people – fieldwork and the Pennsylvania Germans
Authors: Burridge Kate
Published: March 2007

The following is an account of fieldwork experience in the Old Order Mennonite community of Waterloo County, Ontario. The language spoken here is Pennsylvania German and this paper focuses on methodological and ethical challenges that arise for any linguist wanting to study this language in its natural setting. This is a close-knit, ultra-conservative and deeply religious speech community, specifically one that wants to remain apart from the outside world. Even the issue of language survival does not give the linguist a natural role to play. Formal maintenance efforts are not in demand. Pennsylvania German is a language that has been holding its own for nearly 400 years and it is the humble, separate and ‘peculiar’ existence of these speakers that holds the key to the continued existence of this language.
Fieldwork among the Goemai in Nigeria: discovering the grammar of property expressions
Authors: Hellwig Birgit
Published: March 2007

This paper describes fieldwork experiences among the Goemai of Central Nigeria. It first introduces the fieldwork setting, and then focuses on one illustrative example: the investigation of property-denoting (‘adjectival’) expressions. The paper describes the different methods employed, compares them, and evaluates their results. It shows some advantages and disadvantages, and – on this basis – advocates using a combination of methods in order to benefit from each method's advantages while counterbalancing its disadvantages. In particular, the paper argues in favour of a semantics-based approach to fieldwork, illustrating the invaluable insights to be gained from it.
Effects of Population Increase on Cui‐ui Growth and Maturation
Authors: Scoppettone G. Gary , Rissler Peter H.
Published: March 2007

Cui‐ui Chasmistes cujus is endemic to Pyramid Lake, Nevada. The cui‐ui population declined during much of the 20th century as a result of water diversion and the formation of a shallow and virtually impassable delta at the mouth of the Truckee River, its spawning habitat. The population increased more than 10‐fold to more than 1 million adults after access to the river was restored, creating a period of relatively higher density. This change presented the opportunity to test intraspecific density effects on cui‐ui age and length at maturity and on growth. We also compared the year‐class structure of the adult population before and after improved access. At low density, cui‐ui mean age at maturation was 9.2 years for males and 9.6 for females; at high density, it was significantly higher: 11.8 years for males and 12.0 for females. There was no significant change in mean fork length at maturity related to population increase. Growth patterns differed between high and low density, the low‐density fish growing faster than high‐density fish before their respective mean age of maturity; past their mean age at maturity, high‐density fish grew significantly faster than low‐density fish. Fish in both density periods reached similar lengths by about 19–20 years of age. Year‐class structure for both density periods consisted of strong year‐classes, which predominated the adult population for several years.
Field‐Based Estimates of Thermal Tolerance Limits for Trout: Incorporating Exposure Time and Temperature Fluctuation
Authors: Wehrly Kevin E. , Wang Lizhu , Mitro Matthew
Published: March 2007

We used temperature and fish data from streams across Michigan and Wisconsin to estimate upper thermal tolerance limits for brook trout Salvelinus fontinalis and brown trout Salmo trutta. Tolerance limits were estimated for the maximum daily mean temperature (MEANT), maximum daily maximum temperature (MAXT), and maximum daily temperature range (RNGT) at exposure lengths of 1, 3, 7, 14, 21, 28, 35, 42, 49, 56, and 63 d. We found no difference in the upper thermal tolerance limit for brook and brown trout. For time periods of 1–14 d, the upper temperatures tolerated by trout decreased rapidly from 25.3°C to 22.5°C for MEANT and from 27.6°C to 24.6°C for MAXT. For time periods from 21 to 63 d, the upper temperatures tolerated by trout declined more gradually from 22.1°C to 21.0°C for MEANT and from 24.2°C to 22.9°C for MAXT. The 7‐d upper tolerance limit was 23.3°C for MEANT and 25.4°C for MAXT. The maximum RNGT tolerated by trout varied as a function of mean temperature and length of exposure. Our findings suggest that chronic temperature effects as well as temperature fluctuation play an important role in limiting salmonid distributions and therefore should be considered when developing management objectives and water quality standards.
Prediction of stormwater particle loads from impervious urban surfaces based on a rainfall detachment index
Authors: Brodie I.M.
Published: March 2007

This paper makes use of Non-Coarse Particle (NCP) data collected from three different impervious surfaces in Toowoomba, Australia. NCP is defined as suspended solids less than 500 μm in size. NCP loads (in mg/m2) were derived for 24 storms from a galvanized iron roof, a concrete car park and a bitumen road pavement. A scatter plot analysis was used to identify potential correlations between NCP loads and basic rainfall parameters such as rainfall depth and intensity. An exponential-type trend, consistent with many washoff models, was evident between load and average rainfall intensity for all surfaces. However, load data for some storms did not fit this general trend. Various indices, comprising different combinations of basic rainfall parameters, were evaluated as an alternative to rainfall intensity. A composite index, referred to as the Rainfall Detachment Index, was found to be better than average rainfall intensity in explaining a relationship between NCP load and storm rainfall characteristics. The selected rainfall index utilizes 6-minute rainfall intensities and is a variant of the well known Rainfall Erosivity Index (EI30) used for soil erosion estimation.
Identification of sewer pipes to be cleaned for reduction of CSO pollutant load
Authors: Nagaiwa Akihiro , Settsu Katsushi , Nakajima Fumiyuki , Furumai Hiroaki
Published: March 2007

To reduce the CSO (Combined Sewer Overflow) pollutant discharge, one of the effective options is cleaning of sewer pipes before rainfall events. To maximize the efficiency, identification of pipes to be cleaned is necessary. In this study, we discussed the location of pipe deposit in dry weather in a combined sewer system using a distributed model and investigated the effect of pipe cleaning to reduce the pollutant load from the CSO. First we simulated the dry weather flow in a combined sewer system. The pipe deposit distribution in the network was estimated after 3 days of dry weather period. Several specific pipes with structural defect and upper end pipes tend to have an accumulation of deposit. Wet weather simulations were conducted with and without pipe cleaning in rainfall events with different patterns. The SS loads in CSO with and without the pipe cleaning were compared. The difference in the estimated loads was interpreted as the contribution of wash-off in the cleaned pipe. The effect of pipe cleaning on reduction of the CSO pollutant load was quantitatively evaluated (e.g. the cleaning of one specific pipe could reduce 22% of total CSO load). The CSO simulations containing pipe cleaning options revealed that identification of pipes with accumulated deposit using the distributed model is very useful and informative to evaluate the applicability of pipe cleaning option for CSO pollutant reduction.
A performance investigation of small-bore sewers
Authors: Memon F.A. , Fidar A. , Littlewood K. , Butler D. , Makropoulos C. , Liu S.
Published: March 2007

This paper describes a full-scale physical model and its application to investigate the effectiveness/performance of small-bore sewers for a range of operational and design parameters. The implementation methodology involves observing the movement of synthetic gross solids in three small bore sewers (150, 100 and 75 mm diameter) for different volumes of simulated flush waves and gradients. The simulated flush waves were generated, using an automated wave sequencer, for three different flush volumes (3, 4.5 and 6 litres). To investigate the impact of solid shape factor, a number of tests were carried out using synthetic solids in combination with toilet tissue paper. In total, more than 1,000 tests were performed for different operational and design parameter combinations. Results obtained to date have confirmed earlier studies, particularly with respect to the role of flush volume in solids transport, and identified the impact of gradient variation and its significance particularly in small-bore sewers receiving low flush volume. Results from the physical model application exercise will be used to propose new design guidelines for wastewater collection systems with specific consideration to new developments and inform the decision support system, currently being developed as part of a research project on water cycle management for new developments (WaND).
Changes in isotope ratios during domestic wastewater production
Authors: Schilperoort R.P.S. , Meijer H.A.J. , Flamink C.M.L. , Clemens F.H.L.R.
Published: March 2007

This paper presents considerations for the application of the natural water isotope method on catchment areas. For the estimation of the amount of infiltration and inflow in sewer systems the paper shows two applications in the Netherlands: one successful application on a relatively small catchment area with a simple geo-hydrological groundwater system and one unsuccessful application in an area that shows a large heterogeneity of δ18O values in groundwater. Also, the paper focuses on the validity of the assumption that the isotopic ratios of drinking water are equal to those of strict domestic wastewater. In the transition from drinking water to strict wastewater it is shown that changes in isotopic composition of the water due to evaporation in common household appliances and effects inside the human body are insignificant. However, the presence of high-efficiency condensing boilers in an area can significantly influence the δ18O value of strict wastewater, especially in winter months. This effect should be taken into account when applying the isotope method in such areas.
The effect of rainfall measurement uncertainties on rainfall–runoff processes modelling
Authors: Stransky D. , Bares V. , Fatka P.
Published: March 2007

Rainfall data are a crucial input for various tasks concerning the wet weather period. Nevertheless, their measurement is affected by random and systematic errors that cause an underestimation of the rainfall volume. Therefore, the general objective of the presented work was to assess the credibility of measured rainfall data and to evaluate the effect of measurement errors on urban drainage modelling tasks. Within the project, the methodology of the tipping bucket rain gauge (TBR) was defined and assessed in terms of uncertainty analysis. A set of 18 TBRs was calibrated and the results were compared to the previous calibration. This enables us to evaluate the ageing of TBRs. A propagation of calibration and other systematic errors through the rainfall–runoff model was performed on experimental catchment. It was found that the TBR calibration is important mainly for tasks connected with the assessment of peak values and high flow durations. The omission of calibration leads to up to 30% underestimation and the effect of other systematic errors can add a further 15%. The TBR calibration should be done every two years in order to catch up the ageing of TBR mechanics. Further, the authors recommend to adjust the dynamic test duration proportionally to generated rainfall intensity.
Sewer solids separation by sedimentation – the problem of modeling, validation and transferability
Authors: Kutzner R. , Brombach H. , Geiger W.F.
Published: March 2007

Sedimentation of sewer solids in tanks, ponds and similar devices is the most relevant process for the treatment of stormwater and combined sewer overflows in urban collecting systems. In the past a lot of research work was done to develop deterministic models for the description of this separation process. But these modern models are not commonly accepted in Germany until today. Water Authorities are sceptical with regard to model validation and transferability. Within this paper it is checked whether this scepticism is reasonable. A framework-proposal for the validation of mathematical models with zero or one dimensional spatial resolution for particle separation processes for stormwater and combined sewer overflow treatment is presented. This proposal was applied to publications of repute on sewer solids separation by sedimentation. The result was that none of the investigated models described in literature passed the validation entirely. There is an urgent need for future research in sewer solids sedimentation and remobilization!
The effect of selection of time steps and average assumptions on the continuous simulation of rainwater harvesting strategies
Authors: Coombes P.J. , Barry M.E.
Published: March 2007

The use of domestic rainwater tanks with back up from mains water supplies in urban areas can produce considerable reductions in mains water demands and stormwater runoff. It is commonplace to analyse the performance of rainwater tanks using continuous simulation with daily time steps and average water use assumptions. This paper compares this simplistic analysis to more detailed analysis that employs 6 minute time steps and climate dependent water demand. The use of daily time steps produced considerable under-estimation of annual rainwater yields that were dependent on tank size, rain depth, seasonal distribution of rainfall, water demand and tank configuration. It is shown that analysis of the performance of rainwater tanks is critically dependent on detailed inputs.
Case Report of Unilateral Clefting: Is Sonic Hedgehog to Blame?
Authors: Delaney Meghan , Boyd Theonia K.
Published: March 2007

We describe the autopsy of a chromosomally normal multiple-anomaly fetus with left side–restricted malformations, terminated after routine screening ultrasound. Autopsy findings were remarkable for severe left-sided craniofacial malformations including a cleft left frontal calavarial bone and an oblique facial cleft. Internal examination showed multiple left-sided malformations including severe left ventricular hypoplasia and interrupted aortic arch. A hypoplastic left lung, an accessory spleen, and an absent left kidney and left ureter were also discovered. Some features of the Smith-Lemli-Opitz Syndrome (SLOS) are found in this fetus, yet the occurrence of left side–restricted anomalies indicates that developmental mechanisms responsible for body laterality are involved. Potential mechanisms leading to this constellation of anomalies include a ciliary defect, side-restricted chromosomal mosaicism, or a teratogenic insult, affecting developmental morphogens, including sonic hedgehog. The sonic hedgehog pathway is important in the molecular mechanisms underlying SLOS and in laterality development in the early embryo.