bluuebunny/crossref_metadata_2025 huggingface dataset:
Aldose reductase gene is associated with diabetic macroangiopathy in Japanese Type 2 diabetic patients
Authors: Watarai A. , Nakashima E. , Hamada Y. , Watanabe G. , Naruse K. , Miwa K. , Kobayashi Y. , Kamiya H. , Nakae M. , Hamajima N. , Sekido Y. , Niwa T. , Oiso Y. , Nakamura J.
Published: July 2006

Aims The aldose reductase (AR) gene, a rate‐limiting enzyme of the polyol pathway, has been investigated as a candidate gene in determining susceptibility to diabetic microangiopathy. However, the association of theARgene with diabetic macroangiopathy has not been investigated. Therefore, the present study was conducted to determine whether genetic variations ofARmay determine susceptibility to diabetic macroangiopathy.

Methods There were 378 Type 2 diabetic patients enrolled in this study. A single nucleotide polymorphism in the promoter region (C‐106T) was genotyped and the AR protein content of erythrocytes measured by ELISA.

Results There were no significant differences in genotypic or allelic distribution in patients with or without ischaemic heart diseases, but there was a significant increase in the frequency of the CT + TT genotype and T allele in patients with stroke (P = 0.019 andP = 0.012). The erythrocyte AR protein content was increased in patients with the CT and TT genotype compared with those with the CC genotype. After adjustment for age, duration of diabetes, body mass index, systolic blood pressure, HbA1c, and serum creatinine, triglycerides, and total cholesterol in multivariate logistic‐regression models, the association between thisARgenotype and stroke remained significant.

Conclusions Our results suggest that the CT or TT genotype of theARgene might be a genetic marker of susceptibility to stroke in Type 2 diabetic patients. This observation might contribute to the development of strategies for the prevention of stroke in Type 2 diabetic patients.
Efficient Semiparametric Estimation of the Periods in a Superposition of Periodic Functions with Unknown Shape
Authors: Gassiat Elisabeth , Lévy‐Leduc Céline
Published: July 2006

Abstract. We consider the estimation of the periods of periodic functions when their shape is unknown and they are corrupted by Gaussian white noise. In the case of a single periodic function, we propose a consistent and asymptotically efficient semiparametric estimator of the period. We then study the case of a sum of two periodic functions of unknown shape with different periods and propose semiparametric estimators of their periods that are consistent and asymptotically Gaussian.
Glial fibrillary acidic protein immunoreactivity in the rat suprachiasmatic nucleus: circadian changes and their seasonal dependence
Authors: Gerics Balázs , Szalay Ferenc , Hajós Ferenc
Published: July 2006

The pacemaker of the biological clock, the suprachiasmatic nucleus (SCN) of the hypothalamus, was studied in intact male rats to determine its immunoreactivity to glial fibrillary acidic protein (GFAP), a specific marker of astrocytes. Animals were kept under 12‐h light–dark cycles in synchrony with day–night periods. Immunohistochemical reactions were carried out at midday and late at night in both winter (January) and summer (July). In winter, GFAP immunoreactivity was found to be low during the day and high at night. The findings were reversed in summer, when GFAP immunoreactivity was high during the day and low at night. Increased GFAP immunoreactivity appeared in the form of an abundance of thick immunopositive fibres rather than of cell bodies. This was interpreted as a hypertrophy of pre‐existing astrocytes due to alternating photic stimulation conveyed by retinofugal fibres to the SCN.

The observed seasonal reversal in the direction of GFAP oscillations raises the possibility that a circannual timer exists outside the SCN.
Total sleep deprivation inhibits the neuronal nitric oxide synthase and cytochrome oxidase reactivities in the nodose ganglion of adult rats
Authors: Chang Hung‐Ming , Wu Un‐In , Lin Tzer‐Bin , Lan Chyn‐Tair , Chien Wei‐Ching , Huang Wei‐Ling , Shieh Jeng‐Yung
Published: July 2006

Sleep disorders are a form of stress associated with increased sympathetic activity, and they are a risk factor for the occurrence of cardiovascular disease. Given that nitric oxide (NO) may play an inhibitory role in the regulation of sympathetic tone, this study set out to determine the NO synthase (NOS) reactivity in the primary cardiovascular afferent neurons (i.e. nodose neurons) following total sleep deprivation (TSD). TSD was performed by the disc‐on‐water method. Following 5 days of TSD, all experimental animals were investigated for quantitative nicotinamine adenine dinucleotide phosphate‐diaphorase (NADPH‐d, a co‐factor of NOS) histochemistry, neuronal NOS immunohistochemistry and neuronal NOS activity assay. In order to evaluate the endogenous metabolic activity of nodose neurons, cytochrome oxidase (COX) reactivity was further tested. All the above‐mentioned reactivities were objectively assessed by computerized image analysis. The clinical significance of the reported changes was demonstrated by alterations of mean arterial blood pressure (MAP). The results indicated that in normal untreated rats, numerous NADPH‐d/NOS‐ and COX‐reactive neurons were found in the nodose ganglion (NG). Following TSD, however, both the labelling and staining intensity of NADPH‐d/NOS as well as COX reactivity were drastically reduced in the NG compared with normal untreated ganglions. MAP was significantly higher in TSD rats (136 ± 4 mmHg) than in normal untreated rats (123 ± 2 mmHg). NO may serve as an important sympathoinhibition messenger released by the NG neurons, and decrease of NOS immunoexpression following TSD may account for the decrease in NOS content. In association with the reduction of NOS activity, a defect in NOS expression in the primary cardiovascular afferent neurons would enhance clinical hypertension, which might serve as a potential risk factor in the development of TSD‐relevant cardiovascular disturbances.
Life‐history traits and ontogenetic colour change in an arboreal tropical python, Morelia viridis
Authors: Wilson D. , Heinsohn R. , Wood J.
Published: July 2006

The Pythonidae are a widely distributed group of snakes that fill a variety of niches in Africa, Asia and Australasia. We used mark–recapture techniques to describe the life‐history traits and colour change in the green python Morelia viridis, a species that is popular in the captive pet industry but poorly known in the wild. Modelling of growth rates revealed that males and females reach sexual maturity after 2.4 and 3.6 years, respectively, and are predicted to live for at least 15 years. Extrapolation from small individuals revealed a highly seasonal breeding period with hatching in late November. However, few hatchlings were recorded in any one year, suggesting that adults do not breed every year. The adult sex ratio did not differ from parity, but immature females outnumbered immature males. Approximately 50% of all snakes captured were adult sized. Sexual dimorphism was not detected in the adults, but juvenile females have larger heads than males. Ontogenetic colour change (OCC) from yellow to green occurred between 53 and 59 cm and, based on growth rates, occurs at c. 1 year of age. This change took place rapidly without an associated shedding of skin. Green pythons have a slow life history, and populations may be vulnerable to removal of individuals for the captive pet trade. They also provide excellent opportunities for examining the evolutionary significance of OCC.
RNA interference in pain research
Authors: Röhl Thomas , Kurreck Jens
Published: July 2006

Within the course of only the last few years, RNA interference (RNAi) has been established as a standard technology for investigation of protein function and target validation. The present review summarizes recent progress made in the application of RNAi in neurosciences with special emphasis on pain research. RNAi is a straightforward method to generate loss‐of‐function phenotypes for any gene of interest. In mammals, silencing is induced by small interfering RNAs (siRNAs), which have been shown to surpass traditional antisense molecules. Due to its high specificity, RNAi has the potential for subtype selective silencing of even closely related genes. One of the major challenges for in vivo investigations of RNAi remains efficient delivery of siRNA molecules to the relevant tissues and cells, particularly to the central nervous system. Various examples will be given to demonstrate that intrathecal application of siRNAs is a suitable approach to analyse the function of receptors or other proteins that are hypothesized to play an important role in pain signalling. Intensive efforts are currently ongoing to solve remaining problems such as the risk of off‐target effects, the stability of siRNA molecules and their efficient delivery to the CNS. RNAi has thus demonstrated that it is an extremely valuable tool for the development of new analgesic drugs.
Day Care Service Use Is Associated with Lower Mortality in Community‐Dwelling Frail Older People
Authors: Kuzuya Masafumi , Masuda Yuichiro , Hirakawa Yoshihisa , Iwata Mitsunaga , Enoki Hiromi , Hasegawa Jun , Iguchi Akihisa
Published: July 2006

OBJECTIVES: To clarify the association between day care service use and 21‐month mortality in community‐dwelling frail older people.

DESIGN: Prospective cohort study (the Nagoya Longitudinal Study for Frail Elderly).

SETTING: Community‐based.

PARTICIPANTS: One thousand six hundred seventy‐three community‐dwelling older people (540 men, 1,133 women).

MEASUREMENTS: Data included the clients' demographic characteristics; depression as assessed using the short version of the Geriatric Depression Scale; a rating for basic activities of daily living (ADLs); comorbidity; number of prescribed medications and physician‐diagnosed chronic diseases; use of home‐care services, including day care, visiting nurse, and home‐help services; and number of regular medical checkups. Survival analysis of 21‐month mortality was conducted using Kaplan‐Meier curves and multivariate Cox proportional hazards models.

RESULTS: Of the 1,673 participants, 726 were day care service users at baseline, and 268 (94 day care service users, 174 nonusers) died during the 21‐month follow‐up. Multivariate Cox regression models adjusting for potential confounders showed that day care service use was associated with reduction in mortality. Subgroup analysis demonstrated that day care service use was associated with less risk of mortality in subjects who were female; were in the youngest age group (65–74); had higher ADL scores, lower comorbidity, depression, no dementia; and used a visiting nurse service. Participants using day care service two and three times or more a week had 63% or 44% lower relative hazard ratios, respectively, than participants not using the service.

CONCLUSION: Among community‐dwelling frail older people, day care service use two or more times per week was associated with 44% to 63% lower 21‐month mortality.
The Effect of Urinary Incontinence on Quality of Life in Older Nursing Home Residents
Authors: DuBeau Catherine E. , Simon Samuel E. , Morris John N.
Published: July 2006

OBJECTIVES: To determine whether nursing home residents with urinary incontinence (UI) have worse quality of life (QoL) than continent residents, whether the relationship between UI and QoL differs across strata of cognitive and functional impairment, and whether change in continence status is associated with change in QoL.

DESIGN: Retrospective cohort study using a Minimum Data Set (MDS) database to determine cross‐sectional and longitudinal (6 month) associations between UI and QoL.

SETTING: All Medicare‐ or Medicaid‐licensed nursing homes in Kansas, Maine, Mississippi, New York, and South Dakota during 1994 to 1996.

PARTICIPANTS: All residents aged 65 and older, excluding persons unable to void or with potentially unstable continence or QoL status (recent nursing home admission, coexistent delirium, large change in functional status, comatose, near death).

MEASUREMENTS: UI was defined as consistent leakage at least twice weekly over 3 months and continence as consistent dryness over 3 months. QoL was measured using the validated MDS‐derived Social Engagement Scale.

RESULTS: Of 133,111 eligible residents, 90,538 had consistent continence status, 58,850 (65%) of whom were incontinent. UI was significantly associated with worse QoL in residents with moderate cognitive and functional impairment. New or worsening UI over 6 months was associated with worse QoL (odds ratio=1.46, 95% confidence interval=1.36–1.57) and was second only to cognitive decline and functional decline in predicting worse QoL.

CONCLUSION: This is the first study to quantitatively demonstrate that prevalent and new or worsening UI decreases QoL even in frail, functionally and cognitively impaired nursing home residents. These results provide a crucial incentive to improve continence care and quality in nursing homes and a rationale for targeting interventions to those residents most likely to benefit.
Fragmented, Long‐Duration, Low‐Amplitude Electrograms Characterize the Origin of Focal Atrial Tachycardia
Authors: DE GROOT NATASJA M.S. , SCHALIJ MARTIN J.
Published: July 2006

Background: Focal atrial tachycardias (FAT) originate from areas with poor cell‐to‐cell coupling. Due to cellular uncoupling extracellular potentials become fractionated. The degree of fragmentation may be used to identify the site of origin of FAT prior to catheter ablation. We studied electrical fragmentation in relation to the distance to the site of earliest activity during FAT.

Methods: Three‐dimensional (3‐D) electroanatomical activation/voltage maps obtained from patients (n = 15: 6 male, age 40 ± 14 (19–72) years) referred for catheter ablation of FAT were analyzed. Bipolar atrial potentials (BP) were categorized according to the number of deflections. The peak‐to‐peak amplitude and the time interval between the first and last deflection (fractionation duration) of each BP were measured.

Results: Eighteen different atrial tachycardias (AT) (CL 346 ± 109 [190–550]) msec were analyzed. The incidence of single potentials ranged from 30 to 81 (59 ± 16)%. The occurrence of double and fractionated potentials ≤2 cm of the site of earliest activity (“focal area”) was higher compared to the remainder of the atria (67 ± 22% vs 34 ± 14%, P < 0.001). Focal area potentials were characterized by a longer duration (49 ± 22 msec vs 34 ± 17 msec, P < 0.001) and a lower peak‐to‐peak amplitude (0.51 ± 0.43 [0.12–1.7] mV vs 0.94 ± 0.69 [0.22–2.58] mV, P = 0.03). Fractionation was not associated with FAT cycle length (r =−0.26, P = 0.29) or left atrial diameter (r = 0.47, P = 0.30).

Conclusion: Significant differences in fractionation, fractionation duration, and peak‐to‐peak‐amplitude of atrial potentials between the focal area and the remainder of the atria exist. Fractionation and voltage mapping can be used, besides activation mapping, to identify the site of origin of FAT during catheter ablation.
Usefulness of Live/Real Time Three‐Dimensional Transthoracic Echocardiography in the Assessment of Atrioventricular Septal Defects
Authors: Singh Anurag , Romp Robb L. , Nanda Navin C. , Rajdev Sanjay , Mehmood Farhat , Baysan Oben , Patel Vinod , Duncan Kurt
Published: July 2006

We studied nine patients (five newborns and infants, two children, and two adults) with atrioventricular septal defects (four complete, one intermediate, and four partial) utilizing live/real time three‐dimensional transthoracic echocardiography (3DTTE) and a 4‐MHz matrix array transducer. In all patients, 3DTTE provided additional morphological and/or functional information as compared to standard two‐dimensional transthoracic echocardiography (2DTTE). 3DTTE may be a useful supplement to 2DTTE in the assessment of atrioventricular septal defects.
Aortic Valvular Regurgitation: Prevalence and Clinical Characteristics in a Predominantly Obese Adult Population Not Taking Anorexigens
Authors: Gardin Julius M. , Constantine Ginger , Davis Kelly , Leung Cyril , Reid Cheryl L.
Published: July 2006

Background: We recently reported the prevalence of aortic regurgitation (AR) by Doppler echocardiography (echo) in obese subjects to be higher than in some previous reports. Objective: To describe the prevalence of AR in an obese population not taking anorexigens as a function of demographic characteristics, cardiovascular risk factors, and other potential predictors. Methods: In 539 adult subjects, cardiovascular status was evaluated by medical history, physical examination, and Doppler echocardiograms performed according to a standardized imaging protocol. Echocardiographic readers were blinded as to each subject's medical and medication histories. Associations of AR with demographic and comorbid factors were examined. Results: Subjects had a mean (± SD) body mass index (BMI) of 35 ± 7 kg/m2, and were predominantly white (87.6%), females (74%), with a mean age of 47 ± 12 years. AR by Food and Drug Administration criteria (≥mild) was present in 4.1% of the subjects. Covariates significantly associated with AR were increasing age (P < 0.001), presence of a history of hypertension (P = 0.001), left ventricular (LV) internal dimensions (P < 0.005), and tricuspid and mitral regurgitation grade (P < 0.001). Conclusions: Clinical and Doppler echo evaluation of a large, predominantly obese, adult population revealed that AR was more prevalent than in some previous reports and was highly correlated with increased age, presence of a history of hypertension, LV internal dimensions, tricuspid and mitral regurgitation.
Effect of habitat fragmentation on spawning migration of brown trout (Salmo truttaL.)
Authors: Gosset C. , Rives J. , Labonne J.
Published: July 2006

Abstract – Human‐induced habitat alteration is one of the main causes of the decline of freshwater fish populations. The watershed of the River Bidasoa (Spain) is an example of heavily fragmented habitat. The local brown trout (Salmo truttaL.) population is disturbed, with evidence of poor recruitment as well as low adult densities in the main stem. Forty male and female adult migratory trout were tagged with external or internal radio transmitters and released. Fixed stations with data loggers and mobile antennae were used with daily surveys to track fish movements during the migration and spawning period (3 months). Migration distances did not exceed 10 km, and half of the fish never entered a tributary in the study area. Fragmentation because of weirs on the main stem apparently prevented fish from reaching their spawning destination. Fish that entered the tributaries were first confronted with an accessibility problem because of low discharge. However, each fish chose one tributary, without making attempts to run up in other tributaries. Once in the tributary, fish were restrained in their upstream movements by dams. The study area appeared to be isolated from the vast upper part of the watershed. Within the study area, upper parts of tributaries also seemed strongly disconnected from the main stem. This study illustrates the negative impact of river fragmentation onS. truttamigration pattern. Population sustainability can be directly affected through the low availability of spawning grounds for migratory fish. Long‐term effects of fragmentation may cause reproductive isolation within watersheds, which in the case of trout also means isolated phenotypic population units.
Intergalactic C iv absorption at redshifts 5.4 to 6
Authors: Ryan-Weber Emma V. , Pettini Max , Madau Piero
Published: July 2006

We report the discovery of a strong C ivλλ1548, 1550 absorption system at zabs= 5.7238 in the near-infrared spectrum (J-band) of the zem= 6.28 QSO SDSS J1030+0524. These observations, obtained with the Infrared Spectrometer And Array Camera (ISAAC) on the European Southern Observatory Very Large Telescope (ESO VLT), demonstrate that, with modern instrumentation, QSO absorption line spectroscopy can be successfully extended to near-infrared wavelengths to probe the intergalactic medium near the end of the reionization epoch. Although the statistics of this pilot study are limited, the mass density of triply ionized carbon implied by our data is comparable to the values of ΩC IV reported at lower redshifts. Neither the column density distribution of C iv absorbers nor its integral show significant redshift evolution over a period of time which stretches from 1 to 4.5 Gyr after the big bang, suggesting that a large fraction of intergalactic metals may already have been in place at redshifts above 6. Alternatively, the strong C iv system we have detected may be associated with outflowing, highly-ionized, gas from a foreground massive galaxy; deep imaging and spectroscopy of galaxies near the QSO sightline should be able to distinguish between these two possibilities.
The loss of New Zealand's active dunes and the spread of marram grass (Ammophila arenaria)
Authors: Hilton Michael J.
Published: July 2006

Abstract:  This article examines the decline of New Zealand's active dunes in relation to the introduction of marram grass (Ammophila arenaria). The area of active dunes in New Zealand declined from 129 000 ha in the early 1900s to about 39 000 ha in 2000; a reduction of 70%. The extent of active dunes has declined since the 1950s in all regions, particularly in Northland, Auckland and the Manawatu. The loss of active dunes on the west coast of the North Island resulted primarily from the introduction of marram grass, followed by the establishment of Pinus radiata plantations and extensive pastoral farming. Between 1985 and 2005 marram grass extended its range to the detriment of the indigenous foredune flora. Conservation and resource management agencies should urgently identify dune systems for conservation management and marram grass eradication.
Western Policies on Child Labor Abroad
Authors: Pierik Roland , Houwerzijl Mijke
Published: July 2006

Child labor evokes deep emotions and is cause for growing international concern. Most recent global estimates show that 186 million children are engaged in full time economic activity. This paper discusses the possibilities and pitfalls of Western policies that seek to curb child labor abroad. Since such policies aim to combat practices in other societies, policy-makers should be aware of the many relevant differences between developing and developed countries. We discuss three issues that are central to this debate: different conceptions of childhood and the dominance of the Western conception in these debates; the distinction between child work and child labor; and socioeconomic causes of child labor. We then evaluate the implications of these investigations for direct and indirect policy options against child labor abroad.
Cochlear implantation in obstructed cochleas: the effect of the degree of obstruction on the number of activated electrodes and the amount of postoperative speech perception
Authors: Rinia A.B. , Olphen A.F. , Dunnebier E.A.
Published: July 2006

Objective:  With cochlear implantation, insertion of the electrodes can be hampered by cochlear obstructions. The aim of this study was to investigate the effects of these obstructions on the number of activated electrodes and postoperative speech perception.

Study design and setting:  Retrospective analysis of the operation reports and CT‐scans of patients who underwent cochlear implantation, at the Department of Otorhinolaryngology of the University Medical Center of Utrecht (n = 295).

Patients and interventions:  Fifty patients with a certain degree of cochlear obstruction were included. Based on the surgical intervention to overcome these obstructions they were subdivided into first‐, second‐ and third degree obstructions. The number of implanted and activated electrodes was determined.

Main outcome measures:  Three different speech perception tests after 12 months of cochlear implant use.

Results:  The number of activated electrodes significantly diminished with increasing obstruction degree (P < 0.01). This was caused by a lower amount of implanted electrodes combined with a higher amount of switched off electrodes. With a higher degree of obstruction the amount of postoperative speech perception decreased significantly (P < 0.01). This is partly explained by the lower number of activated electrodes and partly explained by the fact that a higher obstructions degree correlates with a higher degree of (retro‐) cochlear pathology. Significantly more electrodes can be inserted into the severely obstructed cochlea using a Double Array Cochlear Implant.

Conclusion:  Cochlear obstructions pose a surgical threat and negatively influence the postoperative speech perception results. Fortunately, due to surgical techniques, first and second degree obstructed cochleas can often be bypassed. Implanting of a Double Array implant brightens the prospects of patients with third (severe) degree obstructed cochleas.
A comparison of temporal bone fracture classification systems
Authors: Rafferty M.A. , Mc Conn Walsh R. , Walsh M.A.
Published: July 2006

Objectives:  To compare the traditional and otic capsule classification system of temporal bone fractures for clinical relevance.

Design:  A retrospective review of all patients with a radiological diagnosis of a skull‐base fracture over a 5‐year period.

Setting:  All patients were seen at Beaumont Hospital, the national tertiary referral centre for Neuro‐otology.

Participants:  Patients with a clinical diagnosis of skull fracture were identified from the hospitals in patient enquiry (HIPE) database. Of 338 patients, 31 (9%) were identified as having a temporal bone fracture on high‐resolution CT scanning.

Main outcome measures:  The rate and distribution of each major clinical complications within each classification system to establish if either one was more clinically useful.

Results:  Fractures were classified as mixed in 14 (45%), longitudinal in 9 (29%) and horizontal in 8 (26%). Alternatively, 2 (7%) were otic capsule violating and 29 (93%) were otic capsule sparing. Seventeen patients (54.8%) sustained a hearing loss. Seven patients (23%) sustained a facial nerve injury. Four (13%) developed a cerebrospinal fluid (CSF) leak. Of all clinical findings only sensorineural hearing loss occurred significantly more often in the horizontal as opposed to the longitudinal group (P = 0.029) and in the otic violating as opposed to the otic sparing group (P = 0.013).

Conclusions:  We acknowledge that the relatively small size of our cohort diminishes the statistical power of our conclusions. However, we found that the otic capsule‐based classification system was not significantly better than the traditional system in predicting the likelihood of sustaining specific injuries from fractures of the temporal bone.
Effect of Chickpea, Broad Bean, or Isolated Soy Protein Additions on the Physicochemical and Sensory Properties of Biscuits
Authors: Rababah Taha M. , Al‐Mahasneh Majdi A. , Ereifej Khalil I.
Published: July 2006

ABSTRACT:  This study evaluated the effectiveness of substituting different concentrations of chickpea flour, broad bean flour, or isolated soy protein (ISP) on the physicochemical and sensory properties of biscuits. Fortification processes were conducted by substituting specified concentrations (3%, 6%, 9%, and 12%) of both broad bean and chickpea and (3%, 6%, and 9%) ISP from the total percent of wheat flour (100%). Proximate chemical analysis results of biscuits showed that fortification increased protein contents from 16.57% to 22.84%. Results indicated that fortification decreased spread factor compared with the control. Sensory and instrumental color results showed that fortified chickpea increased the lightness, while fortification with broad bean or ISP increased the darkness. Descriptive results showed that as the fortified ISP and chickpea ratios increased most of liking and just about right (JAR) attributes decreased, while they increased for fortified broad bean. Descriptive analysis also showed that 3% of fortified ISP and chickpea or 12% of broad bean provided the best quality ratios within each type of fortification. Consumer results showed that no significant differences of fortification of soy protein isolate (3%), chickpea (3%), or broad bean (12%) and the control of sensory quality attributes of liking and JAR were found except for overall flavor and color. Fortification of chickpea and broad bean flour as well as ISP could be used in production of high‐protein biscuits.
Nonlinear Dynamics and Control of a Pneumatic Vibration Isolator
Authors: Heertjes Marcel , van de Wouw Nathan
Published: July 2006

The nonlinear dynamics of a single-degree-of-freedom pneumatic vibration isolator are studied. Based on a physical model, a nonsymmetric stiffness nonlinearity is derived to describe the stiffness property of the isolator. For a full nonlinear pneumatic isolator model, the response to two different types of disturbances is studied: forces applied to the isolated payload and base vibrations. The dynamic behavior of the isolator in case of a disturbance applied to the payload is studied using the generalized force-mobility function and features coexisting steady-state responses and a superharmonic resonance. Base vibrations transmitted via the isolator are studied on the basis of the generalized transmissibility function again showing rich nonlinear dynamic behavior. The presence of a nonsymmetric nonlinearity also induces high-energy low-frequency response to multiple high-frequency excitation. For both types of excitation, the nonlinear behavior is seriously compromising the performance of the isolator. To avoid any expression of nonlinearity whatsoever and, at the same time, to enhance the performance of the passive isolator, an overall nonlinear control design is proposed. It consists of a linear PID-based controller together with a nonlinear computed torque controller (CTC). For either linear or nonlinear control, the isolator performance is quantified in terms of generalized force mobility and transmissibility. The latter with a special focus on multiple high-frequency excitation.
A State Space Formulation for Moving Loads Identification
Authors: Zhu X. Q. , Law S. S. , Bu J. Q.
Published: July 2006

A new moving load identification method formulated in state space with regularization on the solution is presented. The bridge deck is modeled as an orthotropic rectangular plate, and the loads are modeled as a group of loads moving on top of the bridge deck at a fixed distance and at a constant speed. The Hamilton principle and the modal superposition principle are included in the formulation. Numerical simulations and experimental tests are employed for the verification and illustration on the effectiveness of the proposed method. The effects of different sensor location, different load path eccentricity, different types of measured information, and measurement noise have been investigated, and the effect of the aspect ratio of the bridge deck is also studied. It is concluded that nine sensors collecting information from nine vibration modes would give reasonably accurate identified results over the practical range of aspect ratio of a modern bridge deck. Acceleration responses are preferred over the velocity and strain responses in this study, and the same type of response should be collected for the same supporting beam in the longitudinal direction.
Piezoelectric Active Sensor Self-Diagnostics Using Electrical Admittance Measurements
Authors: Park Gyuhae , Farrar Charles R. , Rutherford Amanda C. , Robertson Amy N.
Published: July 2006

This paper presents a piezoelectric sensor self-diagnostic procedure that performs in situ monitoring of the operational status of piezoelectric materials used for sensors and actuators in structural health monitoring (SHM) applications. The sensor/actuator self-diagnostic procedure, where the sensors/actuators are confirmed to be functioning properly during operation, is a critical component to successfully complete the SHM process with large numbers of active sensors typically installed in a structure. The premise of this procedure is to track the changes in the capacitive value of piezoelectric materials resulting from the degradation of the mechanical/electrical properties and its attachment to a host structure, which is manifested in the imaginary part of the measured electrical admittances. This paper concludes with an experimental example to demonstrate the feasibility of the proposed procedure.
Physicochemical Properties That Enhance Discriminative Antibacterial Activity of Short Dermaseptin Derivatives
Authors: Rotem Shahar , Radzishevsky Inna , Mor Amram
Published: July 2006

Antimicrobial peptides are widely believed to exert their effects by nonspecific mechanisms. We assessed the extent to which physicochemical properties can be exploited to promote discriminative activity by manipulating the N-terminal sequence of the 13-mer dermaseptin derivative K4-S4(1-13) (P). Inhibitory activity determined in culture media against 16 strains of bacteria showed that when its hydrophobicity and charge were changed, P became predominantly active against either gram-positive or gram-negative bacteria. Thus, conjugation of various aminoacyl-lysin moieties (e.g., aminohexyl-K-P) led to inactivity against gram-positive bacteria (MIC50> 50 μM) but potent activity against gram-negative bacteria (MIC50, 6.2 μM). Conversely, conjugation of equivalent acyls to the substituted analog M4-S4(1-13) (e.g., hexyl-M4-P) led to inactivity against gram-negative bacteria (MIC50> 50 μM) but potent activity against gram-positive bacteria (MIC50, 3.1 μM). Surface plasmon resonance experiments, used to investigate peptides' binding properties to lipopolysaccharide-containing idealized phospholipid membranes, suggest that although the acylated derivatives have increased lipophilic properties with parallel antibacterial behavior, hydrophobic derivatives are prevented from reaching the cytoplasmic membranes of gram-negative bacteria. Moreover, unlike modifications that enhanced the activity against gram-positive bacteria, which also enhanced hemolysis, we found that modifications that enhanced activity against gram-negative bacteria generally reduced hemolysis. Thus, compared with the clinically tested peptides MSI-78 and IB-367, the dermaseptin derivative aminohexyl-K-P performed similarly in terms of potency and bactericidal kinetics but was significantly more selective in terms of discrimination between bacteria and human erythrocytes. Overall, the data suggest that similar strategies maybe useful to derive potent and safe compounds from known antimicrobial peptides.
Contribution of Penicillin-Binding Protein Homologs to Antibiotic Resistance, Cell Morphology, and Virulence of
Listeria monocytogenes
EGDe
Authors: Guinane Caitriona M. , Cotter Paul D. , Ross R. Paul , Hill Colin
Published: July 2006

Seven open reading frames, annotated as potential penicillin-binding-protein-encoding genes (lmo0441, lmo0540, lmo1438, lmo1892, lmo2039, lmo2229, and lmo2754), were targeted for insertional mutagenesis in
Listeria monocytogenes
EGDe. These genes were found to contribute in various degrees to β-lactam resistance, cell morphology, or the virulence potential of this organism.
Potential Role of
Veillonella
spp. as a Reservoir of Transferable Tetracycline Resistance in the Oral Cavity
Authors: Ready D. , Pratten J. , Roberts A. P. , Bedi R. , Mullany P. , Wilson M.
Published: July 2006

Twelve out of 96
Veillonella
spp. isolated from oral samples harbored tetracycline resistance genes. The most common resistance gene was
tet
(M). A
tet
(M)-positive
Veillonella dispar
strain was shown to transfer a Tn
916
-like element to four
Streptococcus
spp. by conjugation at a frequency of 5.2 × 10
−6
to 4.5 × 10
−5
per recipient.
In Vitro Activities of Ceftobiprole, Tigecycline, Daptomycin, and 19 Other Antimicrobials against Methicillin-Resistant
Staphylococcus aureus
Strains from a National Survey of Belgian Hospitals
Authors: Denis Olivier , Deplano Ariane , Nonhoff Claire , Hallin Marie , De Ryck Raf , Vanhoof Raymond , De Mendonça Ricardo , Struelens Marc J.
Published: July 2006

The in vitro activities of 22 antimicrobial agents, including ceftobiprole, daptomycin, and tigecycline, against 511 methicillin-resistant
Staphylococcus aureus
(MRSA) isolates from 112 Belgian hospitals were studied by using the CLSI agar dilution method. Isolates were characterized by pulsed-field gel electrophoresis (PFGE) analysis and by PCR detection of determinants of resistance to aminoglycosides, macrolides-lincosamides-streptogramins, and tetracyclines. A representative set of isolates with different PFGE genotypes was further characterized by multilocus sequence typing, determination of staphylococcal cassette chromosome
mec
(SCC
mec
) type, and multiplex PCR for toxic shock syndrome type 1 (TSST-1) and Panton-Valentine leukocidin genes. MRSA isolates belonged to nine epidemic MRSA clones, of which sequence type 45 (ST45)-SCC
mec
IV and ST8-SCC
mec
IV were predominant, accounting for 49 and 20% of isolates, respectively. The distribution of antimicrobial resistance and TSST-1 genes was strongly linked to clonal types. Ceftobiprole, daptomycin, and tigecycline showed high activity against all isolates of these sporadic and epidemic MRSA clones, as indicated by MIC
90
s of 2 mg/liter, 0.5 mg/liter, and 0.25 mg/liter, respectively. The MIC distribution of daptomycin and tigecycline was not different in isolates with decreased susceptibility to glycopeptides or tetracyclines, respectively. Ceftobiprole MICs were not correlated with oxacillin and cefoxitin MICs. These data indicate excellent activity of the newly developed agents ceftobiprole, daptomycin, and tigecycline against MRSA isolates recently recovered from hospitalized patients in Belgium, supporting their therapeutic potential for nosocomial MRSA infections.
Dual Effects of Plant Steroidal Alkaloids on
Saccharomycescerevisiae
Authors: Simons Veronika , Morrissey John P. , Latijnhouwers Maita , Csukai Michael , Cleaver Adam , Yarrow Carol , Osbourn Anne
Published: July 2006

Many
plant species accumulate sterols and triterpenes as antimicrobial
glycosides. These secondary metabolites (saponins) provide built-in
chemical protection against pest and pathogen attack and can also
influence induced defense responses. In addition, they have a variety
of important pharmacological properties, including anticancer activity.
The biological mechanisms underpinning the varied and diverse effects
of saponins on microbes, plants, and animals are only poorly understood
despite the ecological and pharmaceutical importance of this major
class of plant secondary metabolites. Here we have exploited budding
yeast (
Saccharomyces cerevisiae
) to investigate the effects of
saponins on eukaryotic cells. The tomato steroidal glycoalkaloidα
-tomatine has antifungal activity towards yeast, and this
activity is associated with membrane permeabilization. Removal of a
single sugar from the tetrasaccharide chain of α-tomatine
results in a substantial reduction in antimicrobial activity.
Surprisingly, the complete loss of sugars leads to enhanced antifungal
activity. Experiments with α-tomatine and its aglycone
tomatidine indicate that the mode of action of tomatidine towards yeast
is distinct from that of α-tomatine and does not involve
membrane permeabilization. Investigation of the effects of tomatidine
on yeast by gene expression and sterol analysis indicate that
tomatidine inhibits ergosterol biosynthesis. Tomatidine-treated cells
accumulate zymosterol rather than ergosterol, which is
consistent with inhibition of the sterol C
24
methyltransferase Erg6p. However,
erg6
and
erg3
mutants (but not
erg2
mutants) have enhanced resistance to
tomatidine, suggesting a complex interaction of
erg
mutations,
sterol content, and tomatidine
resistance.
Differential Gene Expression in Response to Exposure to Antimycobacterial Agents and Other Stress Conditions among SevenMycobacterium tuberculosis whiB-Like Genes
Authors: Geiman Deborah E. , Raghunand Tirumalai R. , Agarwal Nisheeth , Bishai William R.
Published: July 2006

The sevenMycobacterium tuberculosis whiB-like genes encode small proteins postulated to be transcriptional regulators. A systematic real-time reverse transcription-PCR analysis following exposure to antibiotics and a variety of growth and in vitro stress conditions indicates differential, and in some cases dramatic, transcription modulations for the differentM. tuberculosis whiBfamily members. This information together with biochemical analyses of thewhiB1towhiB7gene products will be important for understanding the biology of this novel family of proteins in mycobacteria and related actinomycetes.
Resistance Levels and
rpoB
Gene Mutations among In Vitro-Selected Rifampin-Resistant
Mycobacterium tuberculosis
Mutants
Authors: Huitric Emma , Werngren Jim , Juréen Pontus , Hoffner Sven
Published: July 2006

The distribution and resistance levels of 189 in vitro-selected rifampin-resistant
Mycobacterium tuberculosis
mutants of Beijing and other genotypes were determined. Apart from a higher amount of codon 522 point mutations and large deletions, a spread of mutations similar to that reported for clinical isolates was seen. Most mutations were correlated with high-level resistance; a lower level, or a MIC of <16 mg/liter, was associated with codon 522 mutations. Multiple mutations were detected in two Beijing mutants.
Candida albicans
and
Candida glabrata
Clinical Isolates Exhibiting Reduced Echinocandin Susceptibility
Authors: Katiyar Santosh , Pfaller Michael , Edlind Thomas
Published: July 2006

A recognized hotspot for mutations conferring reduced echinocandin susceptibility (RES) is residue S645 of
Candida albicans
Gsc1(Fks1). We report that the mutation F641Y is associated with RES in a
C. albicans
isolate. The analogous Fks2 residue is mutated F to V in a
Candida glabrata
RES isolate; the introduction of this mutation into susceptible
C. glabrata
confirmed its role in RES. Y641-equivalent Fks residues were identified in intrinsically RES
Fusarium
species and
Candida guilliermondii
.
Fosmidomycin plus Clindamycin for Treatment of Pediatric Patients Aged 1 to 14 Years with
Plasmodium falciparum
Malaria
Authors: Borrmann Steffen , Lundgren Ingrid , Oyakhirome Sunny , Impouma Bénido , Matsiegui Pierre-Blaise , Adegnika Ayola A. , Issifou Saadou , Kun Jürgen F. J. , Hutchinson David , Wiesner Jochen , Jomaa Hassan , Kremsner Peter G.
Published: July 2006

Fosmidomycin plus clindamycin was shown to be efficacious in the treatment of uncomplicated
Plasmodium falciparum
malaria in a small cohort of pediatric patients aged 7 to 14 years, but more data, including data on younger children with less antiparasitic immunity, are needed to determine the potential value of this new antimalarial combination. We conducted a single-arm study to improve the precision of efficacy estimates for an oral 3-day fixed-ratio combination of fosmidomycin and clindamycin at 30 and 10 mg/kg of body weight, respectively, every 12 hours for the treatment of uncomplicated
P. falciparum
malaria in 51 pediatric outpatients aged 1 to 14 years. Fosmidomycin plus clindamycin was generally well tolerated, but relatively high rates of treatment-associated neutropenia (8/51 [16%]) and falls of hemoglobin concentrations of ≥2 g/dl (7/51 [14%]) are of concern. Asexual parasites and fever were cleared within median periods of 42 h and 38 h, respectively. All patients who could be evaluated were parasitologically and clinically cured by day 14 (49/49; 95% confidence interval [CI], 93 to 100%). The per-protocol, PCR-adjusted day 28 cure rate was 89% (42/47; 95% CI, 77 to 96%). Efficacy appeared to be significantly reduced in children aged 1 to 2 years, with a day 28 cure rate of only 62% for this small subgroup (5/8). The inadequate efficacy in children of <3 years highlights the need for continued systematic studies of the current dosing regimen, which should include randomized trial designs.
Combination Chemotherapy with the Nitroimidazopyran PA-824 and First-Line Drugs in a Murine Model of Tuberculosis
Authors: Nuermberger Eric , Rosenthal Ian , Tyagi Sandeep , Williams Kathy N. , Almeida Deepak , Peloquin Charles A. , Bishai William R. , Grosset Jacques H.
Published: July 2006

The creation of new chemotherapeutic regimens that permit shortening the duration of treatment is a major priority for antituberculosis drug development. In this study, we used the murine model of experimental tuberculosis therapy to determine whether incorporation of the investigational new nitroimidazopyran PA-824 into the standard first-line regimen has the potential to shorten the 6-month duration of treatment. As demonstrated previously, PA-824 alone had significant bactericidal activity over the first 2 months of treatment. Moreover, the substitution of PA-824 for isoniazid led to significantly lower lung CFU counts after 2 months of treatment and to more rapid culture-negative conversion compared to the standard regimen of rifampin, isoniazid, and pyrazinamide. Despite this, there was no difference in the proportion of mice relapsing after completing 6 months of therapy (2 of 19 mice treated with PA-824 in place of isoniazid relapsed versus 0 of 46 mice treated with the standard regimen). Meanwhile, no other PA-824-containing regimen tested was superior to the standard regimen on any assessment. Thus, we were unable to establish a clear role for PA-824 in a treatment-shortening regimen that includes two or more of the current first-line drugs. Future preclinical studies should include the evaluation of novel combinations of PA-824 with new drug candidates in addition to existing antituberculosis drugs for their potential to substantially improve the treatment of both drug-susceptible and multidrug-resistant tuberculosis.
Killing Kinetics of Caspofungin, Micafungin, and Amphotericin B against
Candida guilliermondii
Authors: Cantón Emilia , Pemán Javier , Sastre Macrina , Romero Mónica , Espinel-Ingroff Ana
Published: July 2006

Amphotericin B (AMB), micafungin, and caspofungin MICs, minimal fungicidal concentrations, and time-killing curves were determined in the presence and absence of 10% inactivated serum. AMB was the only agent with consistent killing activity (time required to achieve 99.9% of growth reduction was 2.1 to 3.2 h). The presence of serum enhanced caspofungin activity but lowered those of micafungin and AMB.