bluuebunny/crossref_metadata_2025 huggingface dataset:
Microarray-based comparison of three amplification methods for nanogram amounts of total RNA
Authors: Singh Ruchira , Maganti Rajanikanth J. , Jabba Sairam V. , Wang Martin , Deng Glenn , Heath Joe Don , Kurn Nurith , Wangemann Philine
Published: December 2004

Gene expression profiling using microarrays requires microgram amounts of RNA, which limits its direct application for the study of nanogram RNA samples obtained using microdissection, laser capture microscopy, or needle biopsy. A novel system based on Ribo-SPIA technology (RS, Ovation-Biotin amplification and labeling system) was recently introduced. The utility of the RS system, an optimized prototype system for picogram RNA samples (pRS), and two T7-based systems involving one or two rounds of amplification (OneRA, Standard Protocol, or TwoRA, Small Sample Prototcol, version II) were evaluated in the present study. Mouse kidney (MK) and mouse universal reference (MUR) RNA samples, 0.3 ng to 10 μg, were analyzed using high-density Affymetrix Mouse Genome 430 2.0 GeneChip arrays. Call concordance between replicates, correlations of signal intensity, signal intensity ratios, and minimal fold increase necessary for significance were determined. All systems amplified partially overlapping sets of genes with similar signal intensity correlations. pRS amplified the highest number of genes from 10-ng RNA samples. We detected 24 of 26 genes verified by RT-PCR in samples prepared using pRS. TwoRA yielded somewhat higher call concordances than did RS and pRS (91.8% vs. 89.3% and 88.1%, respectively). Although all target preparation methods were suitable, pRS amplified the highest number of targets and was found to be suitable for amplification of as little as 0.3 ng of total RNA. In addition, RS and pRS were faster and simpler to use than the T7-based methods and resulted in the generation of cDNA, which is more stable than cRNA.
Regulation of adiponectin receptor gene expression in diabetic mice
Authors: Inukai Kouichi , Nakashima Youhei , Watanabe Masaki , Takata Nobuki , Sawa Takahiro , Kurihara Susumu , Awata Takuya , Katayama Shigehiro
Published: December 2004

Adiponectin is an adipocyte-derived factor that plays pivotal roles in lipid and glucose metabolism in muscle and liver. The following two adiponectin receptor types were recently identified: AdipoR1 is abundantly expressed in muscle, whereas AdipoR2 is predominantly expressed in the liver. To clarify the regulation of adiponectin receptor gene expression in diabetic states, we examined mRNA levels of AdipoR1 in the muscles of diabetic animals by Northern blotting. The level of AdipoR1 mRNA was increased ∼2.5-fold in muscle of streptozotocin (STZ) diabetic mice, but the normal level was restored by insulin administration, indicating that insulin has an inhibitory effect on AdipoR1 expression. To confirm this inhibitory effect of insulin, we performed in vitro experiments using C2C12 skeletal muscle cells. Insulin treatment for 24 h decreased AdipoR1 expression by ∼60% in C2C12 cells. In addition, this effect was mediated by the phosphatidylinositol 3-kinase-dependent pathway rather than the mitogen-activated protein kinase pathway. AdipoR1 expression in insulin-resistant diabetic mice was also investigated. AdipoR1 expression was decreased by 36% in type 2 diabetic obese db/db mice compared with lean mice. In contrast, hepatic AdipoR2 expression was not significantly changed in either STZ mice or genetically obese mice. Our results indicate that regulation of AdipoR1, but not that of AdipoR2, may be involved in glucose and lipid metabolism in diabetic states.
Cross talk between the intrarenal dopaminergic and cyclooxygenase-2 systems
Authors: Zhang Ming-Zhi , Yao Bing , McKanna James A. , Harris Raymond C.
Published: December 2004

In mammalian kidney, dopamine produced in the proximal tubule (PT) acts as an autocrine/paracrine natriuretic hormone that inhibits salt and fluid reabsorption in the PT. In high-salt-treated animals, PT dopamine activity increases and inhibits reabsorption, leading to increased salt and fluid delivery to the macula densa (MD) and subsequent natriuresis and diuresis. Regulated cyclooxygenase-2 (COX-2) in the MD represents another intrinsic system mediating renal salt and water homeostasis. Renal cortical COX-2 is inversely related to salt intake, and decreased extracellular NaCl stimulates COX-2 expression in cultured MD/cortical thick ascending limb cells. The current study investigated interactions between renal dopamine and cortical COX-2 systems. In rats fed a control diet, the dopamine precursor l-dihydroxyphenylalanine (l-DOPA) or the DA1 receptor agonist SKF-81297 suppressed cortical COX-2 expression. High salt suppressed cortical COX-2 expression, which was attenuated by inhibition of dopamine production with benserazide or the DA1 receptor antagonist, SCH-23390. In contrast, l-DOPA or the dopamine-metabolizing enzyme inhibitor entacapone suppressed low-salt-induced cortical COX-2 expression. Inhibition of PT reabsorption with the carbonic anhydrase inhibitor acetazolamide suppressed cortical COX-2 expression. In contrast, treatment with distally acting diuretics led to elevation of cortical COX-2. These results indicate that dopamine modulates renal cortical COX-2 expression by modifying PT reabsorption.
Stumbling Over Obstacles in Older Adults Compared to Young Adults
Authors: Schillings A. M. , Mulder Th. , Duysens J.
Published: December 2004

Falls are a major problem in older adults. Many falls occur because of stumbling. The aim of the present study is to investigate stumbling reactions of older adults and to compare them with young adults. While subjects walked on a treadmill, a rigid obstacle unexpectedly obstructed the forward sway of the foot. In general, older adults used the same movement strategies as young adults (“elevating” and “lowering”). The electromyographic responses were categorized according to latencies: short-latency (about 45 ms, RP1), medium-latency (about 80 ms, RP2), and long-latency responses (about 110 ms, RP3; about 160 ms, RP4). Latencies of RP1 responses increased by about 6 ms and of RP2 by 10–19 ms in older adults compared with the young. Amplitudes of RP1 were similar for both age groups, whereas amplitudes of RP2–RP4 could differ. In the early-swing elevating strategy (perturbed foot directly lifted over the obstacle) older adults showed smaller responses in ipsilateral upper-leg muscles (biceps femoris and rectus femoris). This was related to shorter swing durations, more shortened step distances, and more failures in clearing the obstacle. In parallel, RP4 activity in the contralateral biceps femoris was enhanced, possibly pointing to a higher demand for trunk stabilization. In the late-swing lowering strategy (foot placed on the treadmill before clearing the obstacle) older adults showed lower RP2–RP3 responses in most muscles measured. However, kinematic responses were similar to those of the young. It is concluded that the changes in muscular responses in older adults induce a greater risk of falling after tripping, especially in early swing.
Simulations of Saccade Curvature by Models That Place Superior Colliculus Upstream From the Local Feedback Loop
Authors: Walton Mark M. G. , Sparks David L. , Gandhi Neeraj J.
Published: December 2004

When humans or monkeys are asked to make saccades to visual targets accompanied by one or more distractors, the two dimensional trajectory of the saccade will sometimes display significant curvature. Port and Wurtz used dual electrode recordings to show that this phenomenon is associated with activity at more than one site in superior colliculus (SC). The timing and initial direction of the curvature could be predicted by computing a weighted vector average of the normalized activity of the two neurons. As these authors noted, however, this approach does not result in correct predictions of the final direction of curved saccades. We show that the final direction of these movements can be predicted by taking into account the brain stem saccade generator and the local feedback loop. If the output of SC is computed as a weighted vector average of the saccades requested by the activated sites, and this collicular output is interpreted by downstream structures as desired displacement, existing models that place SC upstream from the local feedback loop can generate realistic saccade trajectories, including the final direction. We propose that saccade curvature is the result of a change in the relative level of activity at the two sites, which the brain stem saccade generator interprets as a change in desired displacement.
The Orlicz space of entire sequences
Authors: Rao K. Chandrasekhara , Subramanian N.
Published: December 2004

Let Γ denote the space of all entire sequences and
∧
the space of all analytic sequences. This paper is
devoted to the study of the general properties of Orlicz space
ΓM of Γ.
Viable Podocytes Detach in Experimental Diabetic Nephropathy: Potential Mechanism Underlying Glomerulosclerosis
Authors: Petermann Arndt T. , Pippin Jeffrey , Krofft Ron , Blonski Mary , Griffin Sian , Durvasula Raghu , Shankland Stuart J.
Published: December 2004

Background: A decrease in podocyte number contributes to the development of glomerulosclerosis in diabetic nephropathy. Although podocytes have been detected in the urine in certain glomerular diseases, their viability is poorly understood. Methods: Diabetes was induced in rats with streptozotocin. Urine was collected from control rats (given citrate), and rats with diabetic nephropathy, and cells obtained by centrifugation were resuspended in tissue culture media, and seeded onto collagen-coated tissue culture plates. Cells were grown under standard cell culture conditions ex vivo. Cell number was measured, the cell type in the urine was identified by immunostaining with specific antibodies, and morphology was assessed by light and electron microscopy. Results: Within 24 h, cells obtained from the urine of diabetic rats attached to tissue culture plates ex vivo. Cells were not detected in the urine from control rats. All cells from diabetic rats stained positive for the podocyte-specific proteins synaptopodin, nephrin, podocin and Glepp-1 and negative for mesangial (OX-7), tubular (Tamm-Horsfall protein) and endothelial (RECA) cell antigens. The cell number increased daily, which is consistent with cell growth ex vivo. Conclusions: Rats with diabetic nephropathy shed podocytes into the urine that attach and grow ex vivo. These results are consistent with the detachment of viable podocytes in diabetes and add new perspectives into our understanding of development of glomerulosclerosis in diabetes mellitus.
Inhibition of Nuclear Factor-κB Activation Attenuates Tubulointerstitial Nephritis Induced by Gentamicin
Authors: Volpini Rildo A. , Costa Roberto S. , da Silva Cleonice G.A. , Coimbra Terezila M.
Published: December 2004

Background: Animals treated with gentamicin can show residual areas of interstitial fibrosis in the renal cortex. This study investigated the expression of nuclear factor-ĸB (NF-ĸB), mitogen-activated protein (MAP) kinases and macrophages in the renal cortex and structural and functional renal changes of rats treated with gentamicin or gentamicin + pyrrolidine dithiocarbamate (PDTC), an NF-ĸB inhibitor. Methods: 38 female Wistar rats were injected with gentamicin, 40 mg/kg, twice a day for 9 days, 38 with gentamicin + PDTC, and 28 with 0.15 M NaCl solution. The animals were killed 5 and 30 days after these injections and the kidneys were removed for histological and immunohistochemical studies. The results of the immunohistochemical studies were scored according to the extent of staining. The fractional interstitial area was determined by morphometry. Results: Gentamicin-treated rats presented a transitory increase in plasma creatinine levels. Increased ED-1, MAP kinases and NF-ĸB staining were also observed in the renal cortex from all gentamicin-treated rats compared to control (p < 0.05). The animals killed on day 30 also presented fibrosis in the renal cortex despite the recovery of renal function. Treatment with PDTC reduced the functional and structural changes induced by gentamicin. Conclusions: These data show that inhibition of NF-ĸB activation attenuates tubulointerstitial nephritis induced by gentamicin.
Adiponectin in Patients with Obstructive Sleep Apnea Syndrome: Course and Physiological Relevance
Authors: Harsch I.A. , Wallaschofski H. , Koebnick C. , Pour Schahin S. , Hahn E.G. , Ficker J.H. , Lohmann T.
Published: December 2004

Background: Adiponectin is an adipocyte-derived hormone with anti-inflammatory and insulin-sensitizing properties. Insulin resistance is a typical feature of the obstructive sleep apnea syndrome (OSAS). Objectives: Since nasal continuous positive airway pressure (nCPAP) treatment improves insulin sensitivity in patients with OSAS, we investigated serum adiponectin levels before and during nCPAP treatment to clarify possible interactions between the adiponectin levels and insulin sensitivity in patients with OSAS. Methods: Thirty nondiabetic, obese patients with OSAS (mean age 56.4 ± 11.1 years; apnoea-hypopnoea index (AHI) 46.03 ± 19.57) underwent CPAP treatment. Adiponectin levels and the levels of proinflammatory cytokines and proteins reflecting platelet activation [regulated on activation normally T cell expressed and secreted (RANTES) and soluble P-selectin (sCD62p)], as well as the insulin sensitivity index were measured before, and after 2 days and 3 months of CPAP treatment. Results: Insulin sensitivity increased significantly under nCPAP treatment, whereas adiponectin levels decreased after 2 days of nCPAP treatment, but returned to baseline levels after 3 months of nCPAP treatment. The increase in insulin sensitivity was more pronounced in patients with the highest adiponectin levels at baseline (p = 0.021) after adjustment for body fat (p = 0.003). During treatment, changes in adiponectin levels were highly predictable by the insulin sensitivity index. Conclusions: We found a significant relation between adiponectin and the insulin sensitivity index in overweight patients with OSAS. The lack of a long-lasting change in adiponectin may be explained by the overwhelming influence of the body mass index on adiponectin secretion, which was unchanged during nCPAP treatment.
Model-Based versus Clinical Prediction of the Spirometric Response to Lung Volume Reduction Surgery
Authors: Bloch Konrad E. , Weder Walter , Bachmann Lucas M. , Russi Erich W.
Published: December 2004

Background: Lung volume reduction surgery (LVRS) improves symptoms and lung function in selected patients with severe emphysema. Objectives: We investigated whether models based on physiologic and radiologic predictors discriminated patients with a favorable from those with a poor spirometric response to LVRS. Methods: Data of a derivation cohort of 70 patients who had previously undergone LVRS served to develop two types of prediction models, lookup functions and logistic regression equations. Presence or absence of improvement in forced expiratory volume in 1 s (FEV1) ≧300 ml and forced vital capacity (FVC) ≧500 ml represented dichotomous outcomes. The residual volume/total lung capacity ratio, CT-radiological emphysema heterogeneity scores and diffusing capacity, a marker of emphysema severity, were the predictors. Models were used to predict spirometric outcomes for a validation cohort of 60 emphysema patients referred for LVRS. Furthermore, the surgeon preoperatively estimated outcomes based on all available clinical data but blinded to model predictions. Spirometric changes within 6 months following surgery were compared to predictions. Results: Median FEV1 in the validation cohort increased from 0.69 to 1.00 liters (+41%), and FVC from 2.07 to 2.78 liters (+29%; p < 0.05 for changes). Lookup functions and logistic regression equations identified patients experiencing major increases in FEV1 ≧300 ml and FVC ≧500 ml with an accuracy quantified by areas under the receiver-operating characteristic curves of 0.72 to 0.76 (all areas >0.5, p < 0.05). Predictions by the surgeon had an accuracy of 0.71 to 0.78 (p = NS vs. models). Conclusions: The accuracy of models based on three predictors was fair and similar to assessment by an experienced surgeon based on all available clinical information. Prediction models may contribute to the consistent assessment of LVRS candidates.
Functional Long-Term Outcome of a Free Jejunal Transplant Reconstruction following Chemoradiotherapy and Radical Resection for Hypopharyngeal and Proximal Oesophageal Carcinoma
Authors: Bergquist Henrik , Ejnell Hasse , Fogdestam Ingemar , Mark Hans , Mercke Claes , Lundell Lars , Ruth Magnus
Published: December 2004

Background/Aims: To evaluate the functional outcome of a reconstruction by a free vascularized jejunal transplant combined with a voice prosthesis after chemoradiotherapy and surgery for proximal oesophageal or hypopharyngeal cancer. Methods: Seven patients (6 men, mean age 52 years, range 28–70) with squamous cell cancer in the proximal oesophagus (n = 6) or the hypopharynx received preoperative chemoradiotherapy (40.8 Gy, cisplatinum and 5-FU) followed by a circumferential pharyngolaryngectomy and resection of the proximal oesophagus. A single-stage reconstruction was carried out with a free jejunal transplant using a microsurgical technique. A tracheojejunal puncture and insertion of a voice prosthesis (Provox I) was performed after 3 months in suitable cases. Results: All operations had a per- and postoperative uneventful course. Five patients were alive after a mean follow-up time of 5 years and 7 months after surgery (range 3 years 4 months to 7 years 10 months), while 2 patients died from metastases within 2 years after surgery. Postoperative examination showed histopathological down-staging in all cases. Relief of dysphagia was achieved in most cases. Good or average speech was recorded in 3 patients. Conclusion: Reconstruction after radical resection for proximal oesophageal and hypopharyngeal cancer can be carried out with low mortality, acceptable morbidity and a promising functional outcome.
Dietary Lipids Modify Intestinal Lipid-Binding Protein RNA Abundance in Diabetic and Control Rats
Authors: Drozdowski L. , Clement L. , Keelan M. , Niot I. , Clandinin M.T. , Agellon L. , Wild G. , Besnard P. , Thomson A.B.R.
Published: December 2004

Background: Lipid-binding proteins have been identified in the enterocyte, including the cytosolic intestinal and liver fatty acid binding proteins (I-FABP and L-FABP, respectively) as well as the brush border membrane fatty acid transporter (FAT). It is unclear whether variations in the type of dietary lipids or diabetes modify the RNA abundance of these proteins. Diabetes is associated with an increased intestinal lipid uptake, and the lipid uptake is greater in rats fed a semisynthetic saturated fatty acid (SFA) as compared with a polyunsaturated fatty acid (PUFA) diet. Methods: Male Sprague-Dawley rats were injected with streptozotocin or control vehicle and fed chow or either SFA or PUFA for 2 weeks. Northern blotting was performed on RNA isolated from jejunal and ileal tissues. Results: In controls, feeding SFA as compared with PUFA reduced the jejunal abundance of I-FABP and L-FABP RNA. In diabetic rats, feeding SFA increased the ileal FAT RNA. Feeding PUFA reduced jejunal L-FABP and ileal FAT RNA in diabetic rats as compared with controls. Conclusions: The enhanced lipid uptakes reported with feeding an SFA diet or with diabetes were not associated with parallel alterations in lipid-binding proteins. We speculate that these lipid-binding proteins act as a storage mechanism for lipids in enterocytes and are not directly involved in lipid uptake.
Recovery after Prolonged Sleep Deprivation: Residual Effects of Slow-Release Caffeine on Recovery Sleep, Sleepiness and Cognitive Functions
Authors: Beaumont Maurice , Batéjat Denise , Coste Olivier , Doireau Philippe , Chauffard Françoise , Enslen Marc , Lagarde Didier , Pierard Christophe
Published: December 2004

A long work schedule often results in sleep deprivation, sleepiness, impaired performance and fatigue. We investigated the residual effects of slow-release caffeine (SRC) on sleep, sleepiness and cognitive performance during a 42-hour recovery period following a 64-hour continuous wakefulness period in 16 healthy males, according to a double-blind, randomised, placebo-controlled, crossover study. Three hundred milligrams of SRC or placebo was given twice a day at 21:00 and 9:00 during the first 48 h of wakefulness. Recovery sleep was analysed with electroencephalography (EEG) and wrist actigraphy, daytime sleepiness with continuous EEG, sleep latency tests and actigraphy and cognitive functions with computerized tests from the NATO AGARD STRES battery. Both drug groups exhibited almost the same sleep architecture with a rebound of slow-wave sleep during both recovery nights and of REM sleep during the second night. Wakefulness level and cognitive functions were similarly impaired in both groups on the first day of recovery and partially returned to baseline on the second. To conclude, SRC appears to have no unwanted side-effects on recovery sleep, wakefulness and cognitive performance after a long period of sleep deprivation and might therefore be a useful choice over other psychostimulants for a long work schedule.
Stent Implantation Activates RhoA in Human Arteries: Inhibitory Effect of Rapamycin
Authors: Guérin Patrice , Sauzeau Vincent , Rolli-Derkinderen Malvyne , Al Habbash Oussama , Scalbert Elizabeth , Crochet Dominique , Pacaud Pierre , Loirand Gervaise
Published: December 2004

In-stent restenosis is a novel pathobiologic process resulting from vascular smooth muscle cell (VSMC) proliferation, migration and excessive matrix production. The present study was designed to assess the activity of RhoA, a major regulator of VSMC proliferation and migration, after stenting and to determine its role in the neointimal formation. Analysis of RhoA activity in an ex vivo organ culture model of human internal mammary arteries demonstrates that stenting induced a time-dependent increase in RhoA activity (4.9 ± 0.4 vs. 1.2 ± 0.2 in control at 28 days, n = 4, p < 0.0001) associated with a concomitant decrease in p27 expression. Treatment of stented arteries with the permeant RhoA inhibitor TAT-C3 (10 µg/ml) or Rho-kinase inhibitors (Y-27632, 10 µmol/l; fasudil, 10 µmol/l) inhibited both neointimal formation and decrease in p27 expression. Rapamycin (1 and 10 nmol/l) also inhibited neointimal formation, and induced a loss of RhoA expression. The inhibitory effect of rapamycin on neointimal thickening is prevented by the dominant active form of RhoA. Our study shows that stent implantation induces maintained RhoA activation and demonstrates that the inhibitory action of rapamycin on RhoA expression plays a key role in its antirestenotic effect.
Pediatric Inflammatory Bowel Disease in Southeastern Norway: A Five-Year Follow-Up Study
Authors: Størdal Ketil , Jahnsen Jørgen , Bentsen Beint S. , Moum Bjørn
Published: December 2004

Objectives: Few prospective population-based studies have been carried out on the incidence of inflammatory bowel disease (IBD). In a population-based study of pediatric IBD in southeastern Norway, patients <16 years at the time of diagnosis were followed up prospectively. The study reports on changes in diagnosis and clinical outcome 5 years after diagnosis. Methods: From 1990 to 1993 new cases of IBD were registered in a population of 174,482 children aged less than 16 years. The patients’ diagnoses were systematically evaluated 1 year after diagnosis and the patients were followed up clinically for up to 5 years after diagnosis. Results: Sixteen cases of Crohn’s disease (CD), 14 cases of ulcerative colitis (UC) and 3 cases of indeterminate colitis (IND) were initially registered. After 1 year IND were reclassified as UC (n = 2) or CD (n = 1). Altogether, 18% (6/33) had their diagnosis changed during the 5 years of follow-up, which yielded a mean annual incidence of 2.7/100,000 for CD and 2.0/100,000 for UC. Of the children with CD, more than 80% had relapses during the 5-year period, and 6 of 18 had surgery. Two-thirds of the children with UC had relapses during the 5-year period, and 3 patients underwent colectomy. Conclusions: An incidence of 4.7/100,000 is comparable to that found in most other studies made in Europe. The relationship between UC and CD in children was found to differ from that in the adult population. One of 5 patients had their diagnosis changed during the follow-up period. Pediatric UC seems to have a more serious course of disease than in the adult IBD population, which may be explained by the higher risk of pancolitis at diagnosis.
The Status of Women and the Quality of Life in Developing Societies
Authors: Clark Cal , Clark Janet
Published: December 2004

This paper applies aggregate data analysis to explore the relationships among the economic development level, the status of women, and the quality of life in developing societies. In particular, it tests the hypothesis that the status of women is positively related to the quality of life even after the effects of economic growth and development are statistically controlled. Our analysis strongly confirms this hypothesis since the status of women in a society appears to rival the economic development level for explaining how good or ill is the quality of life enjoyed by its citizens. We undertook this study from the theoretical perspective that questions conceptualizing and measuring development simply in terms of the level and growth of GNP per capita. Rather, the social needs and quality of life in a society, the presumed consequences of development, are important as well.
Two new species of Hirmocystis Labbé, 1899 (Apicomplexa: Conoidasida) from Coleopteran and Lepidopteran insects in India
Authors: Chatterjee Monali , Haldar Durga
Published: December 2004

This study records the descriptions of the structures and life cycles of two new species of Hirmocystis Labbé, 1899 (Apicomplexa: Conoidasida), H. cleorinis sp. n. and H. corcyris sp. n., from a coleopteran insect, Cleorina sp. and larvae of a lepidopteran, Corcyra cephalonica, respectively.
Advancing Global-and Continental-Scale Hydrometeorology: Contributions of GEWEX Hydrometeorology Panel
Authors: Lawford R. G. , Stewart R. , Roads J. , Isemer H.-J. , Manton M. , Marengo J. , Yasunari T. , Benedict S. , Koike T. , Williams S.
Published: December 2004

Over the past 9 years, the Global Energy and Water Cycle Experiment (GEWEX), under the auspices of the World Climate Research Programme (WCRP), has coordinated the activities of the Continental Scale Experiments (CSEs) and other related research through the GEWEX Hydrometeorology Panel (GHP). The GHP contributes to the WCRP'S objective of “developing the fundamental scientific understanding of the physical climate system and climate processes [that is] needed to determine to what extent climate can be predicted and the extent of man's influence on climate.” It also contributes to more specific GEWEX objectives, such as determining the hydrological cycle and energy fluxes, modeling the global hydrological cycle and its impacts, developing a capability to predict variations in global and regional hydrological processes, and fostering the development of observing techniques, data management and assimilation systems. GHP activities include diagnosis, simulation, and experimental prediction of regional water balances and process and modeling studies aimed at understanding and predicting the variability of the global water cycle, with an emphasis on regional coupled land–atmosphere processes. GHP efforts are central to providing a scientific basis for assessing critical science issues, such as the consequences of climate change for the intensification of the global hydrological cycle and its potential impacts on regional water resources. This article provides an overview of the role and evolution of the GHP and describes scientific issues that the GHP is seeking to address in collaboration with the international science community.
Progress in Heat Watch–Warning System Technology
Authors: Sheridan Scott C. , Kalkstein Laurence S.
Published: December 2004

Among all atmospheric hazards, heat is the most deadly. With such recent notable heat events as the Chicago Heat Wave of 1995, much effort has gone into redeveloping both the methods by which it is determined whether a day will be “oppressive,” as well as the mitigation plans that are implemented when an oppressive day is forecast to occur.

This article describes the techniques that have been implemented in the development of new synoptic-based heat watch–warning systems. These systems are presently running for over two dozen locations worldwide, including Chicago, Illinois; Toronto, Ontario, Canada; Rome, Italy; and Shanghai, China; with plans for continued expansion. Compared to traditional systems based on arbitrary thresholds of one or two meteorological variables, these new systems account for the local human response by focusing upon the identification of the weather conditions most strongly associated with historical increases in mortality. These systems must be constructed based on the premise that weather conditions associated with increased mortality show considerable variability on a spatial scale. In locales with consistently hot summers, weather/mortality relationships are weaker, and it is only the few hottest days each year that are associated with a response. In more temperate climates, relationships are stronger, and a greater percentage of days can be associated with an increase in mortality.

Considering the ease of data transfer via the World-Wide Web, the development of these systems includes Internet file transfers and Web page creation as components. Forecasts of mortality and recommendations to call excessive-heat warnings are available to local meteorological forecasters, local health officials, and other civic authorities, who ultimately determine when warnings are called and when intervention plans are instituted.
Discord and Collaboration between Allies
Authors: Malici Akan
Published: December 2004

Why did France and Great Britain cooperate in Operation Enduring Freedom after September 11, 2001, and fail to achieve cooperation in Operation Iraqi Freedom in March 2003? Operational code analysis is used to test the threat-cooperation proposition that common perceptions of a security externality and common prescriptions toward it lead to cooperation, whereas an absence of common perceptions or prescriptions leads to a lack of cooperation. Operational code analysis is well suited for this task because it conceptualizes the “self in situation,” with the self having diagnostic propensities about a security externality and prescriptive propensities toward this situation. An examination of these propensities in Operations Enduring Freedom and Iraqi Freedom lends strong support for the threat-cooperation proposition.
Hinduism, Christianity, and Liberal Religious Toleration
Authors: Spinner-Halev Jeff
Published: December 2004

The Protestant conception of religion as a private matter of conscience organized into voluntary associations informed early liberalism’s conception of religion and of religious toleration, assumptions that are still present in contemporary liberalism. In many other religions, however, including Hinduism (the main though not only focus of this article), practice has a much larger role than conscience. Hinduism is not a voluntary association, and the structure of its practices, some of which are inegalitarian, makes exit very difficult. This makes liberal religious toleration an awkward fit for Hinduism; granting religious toleration in India undermines equality and autonomy in severe ways. Yet Hinduism is not without its virtues, and has historically been what I call externally tolerant—it has been relatively tolerant of other religions. Liberal toleration, by contrast, is internally tolerant—it is tolerant of religions that fit the Protestant model, while its tolerance of others is considerably more qualified. I briefly speculate at the end of the article about how to combine these two models of toleration.
Modulation of in vitro proliferation kinetics and primitive hematopoietic potential of individual human CD34+CD38–/lo cells in G0
Authors: Srour Edward F. , Tong Xia , Sung Ki Woong , Plett P. Artur , Rice Susan , Daggy Joanne , Yiannoutsos Constantin T. , Abonour Rafat , Orschell Christie M.
Published: December 2004

Whether cytokines can modulate the fate of primitive hematopoietic progenitor cells (HPCs) through successive in vitro cell divisions has not been established. Single human marrow CD34+CD38–/lo cells in the G0 phase of cell cycle were cultured under 7 different cytokine combinations, monitored for proliferation on days 3, 5, and 7, then assayed for long-term culture-initiating cell (LTC-IC) function on day 7. LTC-IC function was then retrospectively correlated with prior number of in vitro cell divisions to determine whether maintenance of LTC-IC function after in vitro cell division is dependent on cytokine exposure. In the presence of proliferation progression signals, initial cell division was independent of cytokine stimulation, suggesting that entry of primitive HPCs into the cell cycle is a stochastic property. However, kinetics of proliferation beyond day 3 and maintenance of LTC-IC function were sensitive to cytokine stimulation, such that LTC-IC underwent an initial long cell cycle, followed by more synchronized shorter cycles varying in length depending on the cytokine combination. Nonobese diabetic/severe combined immunodeficiency (NOD/SCID) transplantation studies revealed analogous results to those obtained with LTC-ICs. These data suggest that although exit from quiescence and commitment to proliferation might be stochastic, kinetics of proliferation, and possibly fate of primitive HPCs, might be modulated by extrinsic factors.
CCR6 expression defines regulatory effector/memory-like cells within the CD25+CD4+ T-cell subset
Authors: Kleinewietfeld Markus , Puentes Fabiola , Borsellino Giovanna , Battistini Luca , Rötzschke Olaf , Falk Kirsten
Published: December 2004

Regulatory CD25+CD4+ T cells (Treg cells) are a central element of peripheral tolerance. Little is known, however, about phenotypic and functional characteristics of these cells with regard to memory. In this study we show that the chemokine receptor CCR6 is expressed on a distinct subset of mouse Treg cells. Similar to their CD25- counterparts, CCR6+ Treg cells exhibit markers of activation, memory, and expansion that are indicative for an effector-memory function. They are memory-like cells, generated in vivo from CCR6-CD25+ T cells after the encounter of antigen. As conventional CD25- effector-memory T cells, they have a high turnover rate and, in contrast to CCR6- Treg cells, they respond rapidly to restimulation in vitro with up-regulation of interleukin 10. CCR6+ Treg cells are enriched in the peripheral blood and accumulate in the central nervous system after induction of experimental autoimmune encephalomyelitis (EAE). This subset therefore seems to represent a population of regulatory effector-memory T cells (TREM), destined to control potentially destructive immune responses directly in inflamed tissues. Importantly, these cells are also present in humans. Here the expression of CCR6 fully cosegregates with CD45RO, an established marker of human memory T cells.
Evidence for a protective role of Mcl-1 in proteasome inhibitor-induced apoptosis
Authors: Nencioni Alessio , Hua Fei , Dillon Christopher P. , Yokoo Rayka , Scheiermann Christoph , Cardone Mike H. , Barbieri Eleonora , Rocco Ilaria , Garuti Anna , Wesselborg Sebastian , Belka Claus , Brossart Peter , Patrone Franco , Ballestrero Alberto
Published: December 2004

Proteasome inhibitors exhibit antitumor activity against malignancies of different histology. Yet, the mechanisms underlying this effect are poorly understood. Recent evidence indicates that antiapoptotic factors may also accumulate as a consequence of exposure to these drugs, possibly reducing their cytotoxicity. These include the Bcl-2 family member Mcl-1, whose down-regulation has been proposed to initiate apoptosis in response to genotoxic stimuli. In this study, we found that proteasome inhibitors release cyotochrome c and second mitochondria-derived activator of caspase (SMAC)/Diablo and trigger the subsequent apoptotic cascade in spite of concomitant Mcl-1 increase. However, our data indicate that subtraction of Mcl-1 during apoptosis, although not required for early release of proapoptotic factors, is probably relevant in speeding up cell demise, since RNA interference-mediated Mcl-1 silencing is lethal in lymphoma cells. Consistent with this, the cytotoxic effects of proteasome inhibitors are enhanced when Mcl-1 increase is impeded. Thus, this study identifies Mcl-1 accumulation as an unwanted molecular consequence of exposure to proteasome inhibitors, which slows down their proapoptotic effects. Pharmacologic or genetic approaches targeting Mcl-1, including therapeutic RNAi, may increase the effectiveness of these compounds. (Blood. 2005;105:3255-3262)
The molecular machinery of autophagy: unanswered questions
Authors: Klionsky Daniel J.
Published: December 2004

Autophagy is a process in which cytosol and organelles are sequestered within double-membrane vesicles that deliver the contents to the lysosome/vacuole for degradation and recycling of the resulting macromolecules. It plays an important role in the cellular response to stress, is involved in various developmental pathways and functions in tumor suppression, resistance to pathogens and extension of lifespan. Conversely, autophagy may be associated with certain myopathies and neurodegenerative conditions. Substantial progress has been made in identifying the proteins required for autophagy and in understanding its molecular basis; however, many questions remain. For example, Tor is one of the key regulatory proteins at the induction step that controls the function of a complex including Atg1 kinase, but the target of Atg1 is not known. Although autophagy is generally considered to be nonspecific, there are specific types of autophagy that utilize receptor and adaptor proteins such as Atg11; however, the means by which Atg11 connects the cargo with the sequestering vesicle, the autophagosome, is not understood. Formation of the autophagosome is a complex process and neither the mechanism of vesicle formation nor the donor membrane origin is known. The final breakdown of the sequestered cargo relies on well-characterized lysosomal/vacuolar proteases; the roles of lipases, by contrast, have not been elucidated, and we do not know how the integrity of the lysosome/vacuole membrane is maintained during degradation.
Efficient fluorescence labeling of a large RNA through oligonucleotide hybridization
Authors: SMITH GLENNA J. , SOSNICK TOBIN R. , SCHERER NORBERT F. , PAN TAO
Published: December 2004

We present an efficient method of introducing fluorophore labels at selected locations in a large RNA. The method is based on specific and highly efficient hybridization between a fluorophore-containing DNA oligonucleotide and a modular hairpin loop replacing a functionally unimportant hairpin loop in the RNA. We demonstrate its feasibility using a 255-nucleotide RNA derived from the catalytic domain of RNase P from Bacillus subtilis. Hybridization of the DNA oligonucleotide to the modular hairpin loop minimally perturbs the structure and function of this RNA. This labeling scheme should be applicable in studies of RNA conformational dynamics by ensemble and single molecule fluorescence methods.
Nonsense-associated alternative splicing of T-cell receptor β genes: No evidence for frame dependence
Authors: MOHN FABIO , BÜHLER MARC , MÜHLEMANN OLIVER
Published: December 2004

Mutations that generate premature translation-termination codons (PTCs) often result in production of alternatively spliced mRNAs. While in many cases, the PTC-causing mutation was found to affect splicing directly by disrupting an exonic splicing enhancer, induction of alternative splicing of TCR-βpre-mRNA has been reported to be specific for mutations that prematurely terminate the open reading frame. During testing of a cyto-nuclear feedback model that would have explained how cytoplasmic translation could influence nuclear splicing of TCR-βtranscripts, control experiments questioned the frame dependence of the nonsense-associated altered splicing (NAS) of TCR-βpre-mRNA. A subsequent detailed analysis of alternatively spliced TCR-βmRNA expressed from different minigene constructs with nonsense, silent, or frame-shift mutations at various positions revealed no correlation between truncation of the reading frame and production of alternatively spliced mRNA. Our study thus contradicts the previously reported PTC specificity of TCR-βNAS and points out the need for systematically testing the PTC specificity in other cases where NAS has been observed.
Extemporaneous Procedures for Dissolving Risedronate Tablets for Oral Administration and for Feeding Tubes
Authors: Dansereau Richard J , Crail Debbie J
Published: December 2004

BACKGROUND:

Risedronate (Actonel, Procter & Gamble Pharmaceuticals) is commercially available only as film-coated tablets. Extemporaneous procedures for dissolving tablets for feeding tubes and for preparation of an oral liquid have not previously been evaluated.

OBJECTIVE:

To evaluate procedures for dissolving risedronate sodium tablets for administration in liquid form and drug recovery following dissolution in cups and following passage through different types of feeding tubes.

METHODS:

Tablets (5 and 35 mg) were individually dispersed in 2 oz of water. After 2 minutes, the solution was stirred for 30 seconds, dispensed, and rinsed with an additional 4 oz of water. The sample was filtered and analyzed by HPLC. Ten replicates were performed using the various cups. Gastrostomy and nasoenteric tubes were flushed with 1 oz of water. Individual tablets were dispersed in 2 oz of water; after 2 minutes, the solution was stirred for 30 seconds and poured through the tube and flushed with 1 oz of water. Samples were filtered and analyzed by HPLC. Ten replicates were performed for each type of feeding tube.

RESULTS:

For cups, the mean amount of drug recovered ranged from 95.7% to 100.5% of the label claim, with a relative standard deviation (RSD) range of 1.1–6.3%. For gastrostomy and nasoenteric tubes, the mean amount of drug recovered ranged from 98.3% to 101.9% of label claim, with an RSD range of 0.9–3.3%.

CONCLUSIONS:

A simple and accurate procedure was developed for dissolving risedronate tablets in water to prepare a liquid formulation for administration orally or through feeding tubes.
Effect of juvenile wood on strength properties and dimensional stability of black spruce medium-density fiberboard panels
Authors: Shi Jun Li , Zhang Shu Yin , Riedl Bernard
Published: December 2004

Strength properties and dimensional stability of medium-density fiberboard (MDF) panels made from black spruce (Picea mariana [Mill.] BSP.) 0–20, 21–40, and over 40 year old fiber were studied. An analysis of covariance (ANCOVA) was performed to examine the differences in modulus of rupture (MOR), modulus of elasticity (MOE), and thickness swell (TS) of the three types of panels, while panel density was treated as a covariate in order to adjust the mean values that were partly attributed to panel density. The results indicate that MOR, internal bond (IB), and water absorption of MDF panels made from 0–20 year old fiber, which contained 100% juvenile wood, were significantly superior to those of panels made from 21–40 and over 40 year old fiber; but linear expansion (LE) of MDF panels made from 0–20 year old fiber was significantly larger than that of panels from the other two age classes. The differences in MOR, IB, water absorption, and LE between panels made from 21–40 and over 40 year old fiber were not significant. The comparisons of panel MOE and TS were relatively dependent on panel density due to existence of interactions among the three age groups.
Influence of grain direction in vibrational wood welding
Authors: Properzi Milena , Leban Jean-Michel , Pizzi Antonio , Wieland Stephanie , Pichelin Frederic , Lehmann Mario
Published: December 2004

Wood grain orientation differences in the two surfaces to be bonded yield bondlines of different strength in no-adhesives wood welding. Longitudinal wood grain bonding of tangential and radial wood sections yields an approximately 10% difference in strength results of the joint. Cross-grain (±90°) bonding yields instead a much lower strength result, roughly half that observed for pieces bonded with the grain parallel to each other. These differences can be explained by the very marked effect that homogeneity of fibre orientation is known to have on fibre–matrix composites. Oak yields lower results than beech and maple and is more sensitive to welding conditions. Differences in both anatomical and wood constituent composition can account for this difference in performance. Contrary to the other wood species, oak always presents joint bondlines where little or no increase in density at the interface is noticed. This explains its somewhat lower strength results. This is based on the different mode of bonding predominant in this species, while the other species present two different modes of bonding. Thus, two types of bondlines are observed by scanning electron microscopy (SEM): (i) bondlines where entangled fibre–matrix composites are formed at the interface and (ii) bondlines in which direct welding of the cell walls occurs, just by fused intercellular material or cell surface material. In this latter case the cells remain flat, without an entangled fibre–matrix composite being formed. This is the almost exclusively predominant case for oak. Both cases and even hybrid cases between the two have also been observed in beech.
Inverse analysis of the transient bound water diffusion in wood
Authors: Olek Wiesław , Perré Patrick , Weres Jerzy
Published: December 2004

The methods so far applied to determine the bound water diffusion coefficient in wood do not provide credible results on this coefficient as well as on the boundary condition. An alternative approach based on the concept of solving the inverse transfer problems was recently applied. Two European species were investigated in the present study. A series of sorption experiments was performed and followed by the numerical identification of the coefficients. Several case studies were carried out for the constant and bound water content dependent diffusion coefficients. The obtained results were validated by comparison to a set of experimental data.