bluuebunny/crossref_metadata_2025 huggingface dataset:
The human skin/chick chorioallantoic membrane model accurately predicts the potency of cosmetic allergens
Authors: Slodownik Dan , Grinberg Igor , Spira Ram M. , Skornik Yehuda , Goldstein Ronald S.
Published: March 2009

Abstract:  The current standard method for predicting contact allergenicity is the murine local lymph node assay (LLNA). Public objection to the use of animals in testing of cosmetics makes the development of a system that does not use sentient animals highly desirable. The chorioallantoic membrane (CAM) of the chick egg has been extensively used for the growth of normal and transformed mammalian tissues. The CAM is not innervated, and embryos are sacrificed before the development of pain perception. The aim of this study was to determine whether the sensitization phase of contact dermatitis to known cosmetic allergens can be quantified using CAM‐engrafted human skin and how these results compare with published EC3 data obtained with the LLNA. We studied six common molecules used in allergen testing and quantified migration of epidermal Langerhans cells (LC) as a measure of their allergic potency. All agents with known allergic potential induced statistically significant migration of LC. The data obtained correlated well with published data for these allergens generated using the LLNA test. The human‐skin CAM model therefore has great potential as an inexpensive, non‐radioactive, in vivo alternative to the LLNA, which does not require the use of sentient animals. In addition, this system has the advantage of testing the allergic response of human, rather than animal skin.
The Caucasian and African skin types differ morphologically and functionally in their dermal component
Authors: Girardeau Sarah , Mine Solène , Pageon Hervé , Asselineau Daniel
Published: March 2009

Abstract:  In the literature, most reported differences between African and Caucasian skin properties concern pigmentation and barrier function of the stratum corneum and related photoprotective properties. However, little is known about differences in morphology and possibly related biological functions. In this study, we investigated: (i) architectural differences of Caucasian and African mammary skin biopsies using microscopy, (ii) comparative constitutive expression of cytokines, matrix metalloproteinase 1 (MMP‐1) and its inhibitors in papillary dermal fibroblast (pF) and reticular dermal fibroblast (rF) cultures in order to reveal biological features. (i) Neither epidermis thickness nor superficial dermis thickness was significantly different in African versus Caucasian subjects. However, the dermal–epidermal junction (DEJ) length in African skin was about threefold that in Caucasian skin. No differences were noticed as regards elastic and collagen fibre organization. (ii) In papillary fibroblast cultures, a significantly higher level of monocyte chemotactic peptide‐1 (MCP‐1) protein was found in cell cultures from African donors when compared with that from Caucasians. With regard to keratinocyte growth factor (KGF), the ratio of papillary to reticular fibroblast expression was found to be twofold greater in cell cultures from African donors compared with that from Caucasian donors. The same trend was found regarding MMP‐1 and tissue inhibitor metalloproteinase protein 1 (TIMP‐1) protein expression. African skin displays a greater convolution of the DEJ and a higher papillary fibroblast activity. These findings reveal that differences between African and Caucasian skin do not only affect upper epidermis but also dermal functions and dermal–epidermal cellular interactions.
Depth profiling of Stratum corneum hydration in vivo: a comparison between conductance and confocal Raman spectroscopic measurements
Authors: Boncheva Mila , De Sterke Johanna , Caspers Peter J. , Puppels Gerwin J.
Published: March 2009

Abstract:  The high‐frequency electrical conductance of tape‐stripped human skin in vivo can be used to evaluate the hydration profile of Stratum corneum (SC). Tape‐stripping provides access to the underlying SC layers, and the conductance of these layers (as measured by the Skicon instrument) correlates well with their water content, as demonstrated by independent confocal Raman spectroscopic measurements. The correlation shows high inter‐individual variance and is not linear over the full measurement range of the instrument, but is helpful to discriminate between dry, normal and highly hydrated SC. The depth profile of hydration in tape‐stripped SC corresponds to the one in intact SC only if the barrier function of the skin is not impaired. Thus, conductometry of tape‐stripped skin must be used in conjunction with a method that allows to estimate the barrier damage inflicted to SC during the tape‐stripping procedure, for example, measurement of the trans‐epidermal water loss. The methodology described here is simple, rapid and minimally invasive, and it employs commercially available instrumentation that is cheap, portable and easy to use. This approach is applicable to in vivo estimation of the SC hydration in studies in the areas of dermatology, skin care and transdermal drug delivery.
Do summer temperatures trigger spring maturation in Pacific lamprey, Entosphenus tridentatus?
Authors: Clemens B. J. , Van De Wetering S. , Kaufman J. , Holt R. A. , Schreck C. B.
Published: March 2009

Abstract –  Pacific lamprey, Entosphenus tridentatus, return to streams and use somatic energy to fuel maturation. Body size decreases, the lamprey mature, spawn, and then die. We predicted that warm, summer temperatures (>20 °C) would accentuate shrinkage in body size, and expedite sexual maturation and subsequent death. We compared fish reared in the laboratory at diel fluctuating temperatures of 20–24 °C (mean = 21.8 °C) with fish reared at cooler temperatures (13.6 °C). The results confirmed our predictions. Lamprey from the warm water group showed significantly greater proportional decreases in body weight following the summer temperature treatments than fish from the cool water group. A greater proportion of warm water fish sexually matured (100%) and died (97%) the following spring than cool water fish (53% sexually mature, 61% died). Females tended to mature and die earlier than males, most obviously in the warm water group.
A Chinese rhesus macaque (Macaca mulatta) model for vaginal Lactobacillus colonization and live microbicide development
Authors: Yu Rosa R. , Cheng Andrew T. , Lagenaur Laurel A. , Huang Wenjun , Weiss Deborah E. , Treece Jim , Sanders‐Beer Brigitte E. , Hamer Dean H. , Lee Peter P. , Xu Qiang , Liu Yang
Published: March 2009

Background  We sought to establish a nonhuman primate model of vaginal Lactobacillus colonization suitable for evaluating live microbial microbicide candidates.

Methods  Vaginal and rectal microflora in Chinese rhesus macaques (Macaca mulatta) were analyzed, with cultivable bacteria identified by 16S rRNA gene sequencing. Live lactobacilli were intravaginally administered to evaluate bacterial colonization.

Results  Chinese rhesus macaques harbored abundant vaginal Lactobacillus, with Lactobacillus johnsonii as the predominant species. Like humans, most examined macaques harbored only one vaginal Lactobacillus species. Vaginal and rectal Lactobacillus isolates from the same animal exhibited different genetic and biochemical profiles. Vaginal Lactobacillus was cleared by a vaginal suppository of azithromycin, and endogenous L. johnsonii was subsequently restored by intravaginal inoculation. Importantly, prolonged colonization of a human vaginal Lactobacillus jensenii was established in these animals.

Conclusions  The Chinese rhesus macaque harbors vaginal Lactobacillus and is a potentially useful model to support the pre‐clinical evaluation of Lactobacillus‐based topical microbicides.
Baboon serum is superior to human or bovine serum albumin for baboon sperm capacitation and zona binding
Authors: Nyachieo A. , Spiessens C. , Chai D.C. , Kiulia N.M. , Mwenda J.M. , D’Hooghe T.M.
Published: March 2009

Background  Baboon in vitro fertilization requires capacitated sperm in appropriate media. In this study, we compared the effect of baboon serum (Bas), human serum albumin (HSA) and bovine serum albumin (BSA) on baboon sperm capacitation.

Methods  Five males (n = 5) were electroejaculated and 43 oocytes retrieved from super‐ovulated female baboons (n = 10). Each sperm sample was assessed for initial motility and concentration before and after swim‐up. For swim‐up, each sperm sample was incubated separately in Biggers–Whitten–Whittingham media containing either BaS, HSA, BSA or without protein supplementation (control). After swim‐up, each sperm aliquot was incubated with two to three oocytes. The number of sperm bound to the zona was evaluated after overnight incubation.

Results  Sperm motility and zona binding was significantly higher after capacitation in media supplemented with BaS than in HSA or BSA or in media without protein supplementation (P < 0.05).

Conclusion  Baboon serum is superior to HSA or BSA for baboon sperm capacitation and zona binding.
Reproductive challenges of a rare grass, Calamagrostis porteri subsp. insperata (Swallen) C. Greene: implications for habitat restoration
Authors: Gibson David J. , Delong Michael , Chandy Shibi , Honu Yohanes A. K.
Published: March 2009

Background: Habitat management for reproductively challenged rare species is a problem when there is insufficient knowledge of their autecology. This study investigated reproductive failure in the rare grass Calamagrostis porteri ssp. insperata (Swallen) C. Greene (Reed bentgrass). Does the management recommendation of high light stimulate clonal growth, flowering, and seed production?

Location: Shawnee National Forest, IL, USA, and in a greenhouse and an experimental garden at Southern Illinois University, Carbondale, IL, USA.

Methods: Clones obtained from the three known Illinois populations were grown in a glasshouse under experimental light and soil moisture treatments. After 3 years, plants from the high light treatment were planted outside in an experimental garden where the light treatments were maintained for two more years. In the field, vegetative and flowering tiller density, canopy cover, and associated biotic and abiotic variables including abundance of co‐occurring plant species were monitored for 5 years. The overhead tree canopy was cleared over a portion of one population.

Results: In the glasshouse, plants increased in size under high light and moist soil, and there were size differences among populations. Sixty‐six per cent (20 of 30) of the genets flowered when planted outdoors under full sunlight but did not produce seed. In the field, flowering only occurred in Calamagrostis growing in the cleared area, but no seed were produced. The plants in the flowering population were smaller than plants in the other two populations. The herbaceous community associated with Calamagrostis in the open diverged from the communities remaining under the shade.

Conclusions: This study highlights the difficulty of managing reproductively challenged rare species. Calamagrostis populations can be managed to enhance clonal growth, but establishment of new populations would require translocation of vegetative material as it is highly unlikely that seed can be obtained.
Why Do People Become Modern? A Darwinian Explanation
Authors: Newson Lesley , Richerson Peter J.
Published: March 2009

A procession of cultural changes, often referred to as “modernization,” is initiated as a society undergoes economic development. But cultural change continues to be rapid in societies that industrialized several generations ago. Much of the change in both developed and developing societies is a progressive abandonment of the norms, values, and beliefs that encourage behavior consistent with the pursuit of genetic fitness. The kin influence hypothesis suggests that these changes are part of a cultural evolutionary process initiated by the replacement of largely kin‐based communities with social groups consisting largely of non‐kin. Kin have an interest in encouraging one another to behave in ways consistent with the pursuit of reproductive success, and a high level of social exchange between kin will tend to maintain norms that prescribe such behaviors. When social exchange between kin is reduced, these norms begin to relax. Cross‐national comparisons of measures that reflect attitudes and behavior support the hypothesis by showing that cultural differences between countries can be substantially explained by their position on a cultural continuum that begins with social networks widening so that they become less kin‐based.
WHEN IT HAPPENS IN A FAMILY: AIDING PARENTS OF SUBSTANCE‐ABUSING ADOLESCENTS*
Authors: Davidson Howard
Published: March 2009

This article first summarizes key data on the scope of teen substance abuse and the lack of teen access to needed treatment services. It then describes how and why attorneys may be helpful to parents who discover their teen's drug or alcohol problem and seek advice and counsel about the legal implications of various actions that can or may be taken. The article explores such issues as parents finding illegal drugs in the house or on their teen's person, various modalities of treatment and how family members are involved, how parents might secure residential evaluations for their youth without the necessity of juvenile court involvement (and why this is important), concerns about placing youth in unlicensed residential treatment facilities, health insurance coverage issues, home drug testing, and how past American Bar Association (ABA) policy on youth drug and alcohol abuse is being followed up with a new ABA project to aid parents of substance‐abusing teenagers and their families.
THE ROAD FROM ADDICTION RECOVERY TO PRODUCTIVITY: ENDING DISCRIMINATION AGAINST PEOPLE WITH ALCOHOL AND DRUG PROBLEMS
Authors: Leis Roberta , Rosenbloom David
Published: March 2009

People with alcohol or other drug problems face discriminatory public and private policies that restrict their access to appropriate health care, employment, and public benefits, discouraging them from seeking treatment, robbing them of hope for recovery, and costing society millions of dollars. Join Together, a project of Boston University School of Public Health, formed a national policy panel in the spring of 2002 to address this discrimination. The panelists developed the two principles and ten recommendations contained in this report, relying principally upon the written and oral testimony they received. Join Together was assisted in this effort by the American Bar Association's (ABA) Standing Committee on Substance Abuse, which facilitated the panel's initial hearing at the ABA's Annual Meeting in August 2002.
MANDATED CUSTODY EVALUATIONS AND THE LIMITS OF JUDICIAL POWER
Authors: O’Connell Mary E.
Published: March 2009

Kelly and Ramsey are clearly correct that a shift from a “how to” approach to custody evaluations to one that asks the more fundamental question “why” is long overdue. However, in addition to assessing the efficacy of custody evaluations (which Kelly and Ramsey propose), the legal system must also clarify the justification for imposing this extensive—and often expensive—intrusion into the privacy of parents. Three possible justifications for these intrusions are examined in this article: privilege, harm, and voluntariness. Is divorce a privilege, rather than a right, and can qualifications (including intrusive and expensive ones) be attached to requesting that privilege? Are custody evaluations instead justified as a means of avoiding harm to children? If a harm justification is asserted, exactly what harm do evaluations prevent, and how do they accomplish this harm avoidance? Finally, given the high value placed on parental cooperation by the family courts, is it simply too perilous for a parent to oppose a custody evaluation if one is suggested, either by the other parent or by the court? If so, are consents to custody evaluations truly voluntary?
Polyganglioradiculoneuritis in a young cat: clinical and histopathological findings
Authors: Henke D. , Vandevelde M. , Oevermann A.
Published: March 2009

An 18‐month‐old European shorthair cat was presented with a two week history of progressive decrease in consciousness, ambulatory tetraparesis, moderate ataxia and generalised decreased‐to‐absent postural reactions. Bilateral facial and nasal hypalgesia, absent menace response and anisocoria were found, and segmental spinal reflexes were normal. Neurological signs progressed to non‐ambulatory tetraparesis, tremor and spinal hyperalgesia. Histopathological examination revealed a mild‐to‐moderate lymphoplasmacytic and histiocytic infiltration, predominantly in the dorsal spinal roots, cranial nerves and ganglia in association with marked demyelination and proliferation of Schwann cells. Neurons and axons were preserved. Lesions were multi‐focal and varied in severity. A predominantly sensory polyganglioradiculoneuritis was diagnosed. This lesion has not been reported previously in cats. Rabies, herpesviruses, feline infectious peritonitis, feline immunodeficiency virus,Toxoplasma gondiiand feline leukaemia virus were excluded as possible aetiologies. Infections by other viruses or an autoimmune disease are discussed.
Correlation of Normal Diastolic Cardiac Function With VO2max in the Metabolic Syndrome
Authors: Chockalingam Anand , Linden Melissa A. , Dellsperger Kevin C. , Thomas Tom R.
Published: March 2009

Morbid obesity and diabetes cause diastolic dysfunction that can be detected by Doppler echocardiography. Patients with the metabolic syndrome could demonstrate early diastolic dysfunction that may influence effort tolerance. A total of 32 patients (17 men) who fulfilled ≥2 of the 5 metabolic syndrome criteria were studied. The average age of patients was 37±2 years. All patients were overweight/obese (mean body mass index of 34.4±0.7 kg/m2), 15 had blood pressure >130/85 mm Hg, 19 had elevated triglyceride levels (>150 mg/dL), and 17 had low high‐density lipoprotein cholesterol levels (men <40 mg/dL, women <50 mg/dL). Maximal exercise was performed using Bruce treadmill protocol with standard stress echocardiography and tissue Doppler. Maximal oxygen consumption (VO2max) was measured using indirect calorimetry. Left ventricular filling pressure was indirectly derived from dividing pulse Doppler early mitral inflow velocity (E) by tissue Doppler early diastolic mitral annular motion (E′) or E/E′. The group’s average treadmill time was 8.06±0.28 minutes, VO2max was 28.6±1.1 mL/kg/min, and 8.2±0.3 metabolic equivalents. None had evidence of myocardial ischemia or systolic or diastolic dysfunction with exercise. Mean “resting” E/E′ and “post‐exercise” E/E′ were 7.01±0.04 and 7.41±0.41, respectively. There was no significant correlation between resting E/E′ and VO2max (r=−0.266; P=.14). The post‐exercise E/E′ significantly correlated with VO2max (r=−0.483; P=.005) and metabolic equivalents (r=−0.487; P=.005). Diastolic function is preserved in early metabolic syndrome. Even in the normal diastolic function range, exercise E/E′ is inversely related to VO2max. Further longitudinal studies are needed to determine whether they develop diastolic dysfunction and related heart failure.
Calcium Isotopes (δ44/40Ca) in MPI‐DING Reference Glasses, USGS Rock Powders and Various Rocks: Evidence for Ca Isotope Fractionation in Terrestrial Silicates
Authors: Amini Marghaleray , Eisenhauer Anton , Böhm Florian , Holmden Chris , Kreissig Katharina , Hauff Folkmar , Jochum Klaus Peter
Published: March 2009

We report δ44/40Ca(SRM 915a) values for eight fused MPI‐DING glasses and the respective original powders, six USGS igneous rock reference materials, the U‐Th disequilibria reference material TML, IAEA‐CO1 (Carrara marble) and several igneous rocks (komatiites and carbonatites). Sample selection was guided by three considerations: (1) to address the need for information values on reference materials that are widely available in support of interlaboratory comparison studies; (2) support the development of in situ laser ablation and ion microprobe techniques, which require isotopically homogenous reference samples for ablation; and (3) provide Ca isotope values on a wider range of igneous and metamorphic rock types than is currently available in the scientific literature. Calcium isotope ratios were measured by thermal ionisation mass spectrometry in two laboratories (IFM‐GEOMAR and Saskatchewan Isotope Laboratory) using 43Ca/48Ca‐ and 42Ca/43Ca‐double spike techniques and reported relative to the calcium carbonate reference material NIST SRM 915a. The measurement uncertainty in both laboratories was better than 0.2‰ at the 95% confidence level. The impact of different preparation methods on the δ44/40Ca(SRM 915a) values was found to be negligible. Except for ML3‐B, the original powders and the respective MPI‐DING glasses showed identical δ44/40Ca(SRM 915a) values; therefore, possible variations in the Ca isotope compositions resulting from the fusion process are excluded. Individual analyses of different glass fragments indicated that the glasses are well homogenised on the mm scale with respect to Ca. The range of δ44/40Ca(SRM 915a) values in the igneous rocks studied was larger than previously observed, mostly owing to the inclusion of ultramafic rocks from ophiolite sections. In particular, the dunite DTS‐1 (1.49 ± 0.06‰) and the peridotite PCC‐1 (1.14 ± 0.07‰) are enriched in 44Ca relative to volcanic rocks (0.8 ± 0.1‰). The Carrara marble (1.32 ± 0.06‰) was also found to be enriched in 44Ca relative to the values of assumed precursor carbonates (< 0.8‰). These findings suggest that the isotopes of Ca are susceptible to fractionation at high temperatures by, as yet, unidentified igneous and metamorphic processes.
Oxidative Stress in COPD and Its Measurement through Exhaled Breath Condensate
Authors: Lee Wei , Thomas Paul S.
Published: March 2009

Oxidative stress and airway inflammation together form a vicious cycle, which is responsible for the disease progression in chronic pulmonary obstructive disease (COPD). The damaging effects of oxidative stress accumulate over the years, causing increased bronchial hyperresponsiveness and inflammation and destruction of airway epithelial cells and impairing the functions of antiproteases and surfactant. Although the lung expresses a number of antioxidants, cigarette smoking and recurrent infections associated with this disease overwhelm this protective mechanism. Studies of antioxidants in COPD have yielded conflicting results, probably due to the compartmentalization of these mediators, and because of the fact that the lung is a difficult organ to sample. Chronic exposure to oxidants upregulates the production of antioxidants, which become depleted during acute exacerbations. Future studies of the pathogenesis of COPD require a noninvasive yet accurate sampling procedure, of which exhaled breath condensate (EBC) is a good candidate. EBC samples the epithelial lining fluid, which contains the local oxidative stress markers in the lung. Oxidative stress markers such as hydrogen ions, hydrogen peroxide, 8‐isoprostanes, thiobarbituric acid reactive products, nitrosothiols, and nitrite/nitrate have been identified in EBC of COPD patients, whereas many other markers of the oxidative‐antioxidative balance have yet to be investigated.
Hematology of healthy Florida manatees (Trichechus manatus)
Authors: Harvey John W. , Harr Kendal E. , Murphy David , Walsh Michael T. , Nolan Elizabeth C. , Bonde Robert K. , Pate Melanie G. , Deutsch Charles J. , Edwards Holly H. , Clapp William L.
Published: March 2009

Background: Hematologic analysis is an important tool in evaluating the general health status of free‐ranging manatees and in the diagnosis and monitoring of rehabilitating animals.

Objectives: The purpose of this study was to evaluate diagnostically important hematologic analytes in healthy manatees (Trichechus manatus) and to assess variations with respect to location (free ranging vs captive), age class (small calves, large calves, subadults, and adults), and gender.

Methods: Blood was collected from 55 free‐ranging and 63 captive healthy manatees. Most analytes were measured using a CELL‐DYN 3500R; automated reticulocytes were measured with an ADVIA 120. Standard manual methods were used for differential leukocyte counts, reticulocyte and Heinz body counts, and plasma protein and fibrinogen concentrations.

Results: Rouleaux, slight polychromasia, stomatocytosis, and low numbers of schistocytes and nucleated RBCs (NRBCs) were seen often in stained blood films. Manual reticulocyte counts were higher than automated reticulocyte counts. Heinz bodies were present in erythrocytes of most manatees. Compared with free‐ranging manatees, captive animals had slightly lower MCV, MCH, and eosinophil counts and slightly higher heterophil and NRBC counts, and fibrinogen concentration. Total leukocyte, heterophil, and monocyte counts tended to be lower in adults than in younger animals. Small calves tended to have higher reticulocyte counts and NRBC counts than older animals.

Conclusions: Hematologic findings were generally similar between captive and free‐ranging manatees. Higher manual reticulocyte counts suggest the ADVIA detects only reticulocytes containing large amounts of RNA. Higher reticulocyte and NRBC counts in young calves probably reflect an increased rate of erythropoiesis compared with older animals.
The Linguistic Similarities of Spanish Heritage and Second Language Learners
Authors: Lynch Andrew
Published: March 2009

Abstract:This article addresses the situation of lower‐proficiency heritage language learners of Spanish in terms of their linguistic similarities to second language learners. The analysis highlights grammatical and lexical features in the oral discourse of Spanish heritage and second language learners at intermediate and advanced levels of study, establishing common linguistic ground between the two groups. Given the similarities, the article emphasizes the current need for courses designed to accommodate lower‐proficiency heritage learners, integrating principles and aspects of second language acquisition theory and pedagogy.
Reflective Practices in Foreign Language Teacher Education: A View Through Micro and Macro Windows
Authors: Geyer Naomi
Published: March 2009

Abstract: As professional development models of teacher education that allow for self‐directed, collaborative, inquiry‐based learning are increasingly replacing more traditional top‐down models, researchers acknowledge the impact of teachers' reflective practices. Although many different types of reflective practices are reported, the differences across such practices have rarely been discussed. This study focuses on a form of reflective practice—classroom observation—and compares graduate teaching assistants' observation of their own classroom performance through two distinct “windows”—an entire class and a targeted teacher‐fronted activity—within the framework of a foreign language (Japanese) teacher education course. Both types of observation have their distinct advantages and reveal different aspects of the teaching process, as is clearly evidenced in the teaching assistants' reports. The study presents a strong rationale for incorporating both whole‐class (macro) and targeted (micro) observations into teacher education programs.
SPECIAL MEETING TO BE HELD AT 41 QUEEN'S GATE, LONDON, S.W.7 ON WEDNESDAY, 2nd JUNE, 1971 at 6.45 p.m.
Authors: STROYAN H. L. G.
Published: March 2009

A Special Meeting convened in accordance with the Bye‐Laws, Chapters XXIII and XXVIII, will be held on Wednesday, 2nd June, 1971, to consider and vote upon (1) a motion by the Council that the amount of the annual contribution be raised to £10, subject to the exceptions listed in Chapter XVII 2(a)‐(a), which are recommended for continuance; and (2) a proposed alteration to the Bye‐Laws, Chapter XVII. These proposals will be moved from the Chair on behalf of the Council.
Complex cardiovascular actions of α‐adrenergic receptors expressed in the nucleus tractus solitarii of rats
Authors: Bhuiyan Mohammad E. R. , Waki Hidefumi , Gouraud Sabine S. , Takagishi Miwa , Cui He , Yamazaki Toshiya , Kohsaka Akira , Maeda Masanobu
Published: March 2009

Although both α1‐ and α2‐adrenergic receptors (ARs) are known to be expressed in the nucleus of the solitary tract (NTS), the functional significance of these receptors is still not fully established. In this study, we microinjected α1‐ and α2‐AR agonists into the NTS of urethane‐anaesthetized Wister rats to study the cardiovascular effects in response to their activation. When the α1‐AR agonist phenylephrine was microinjected into the area where barosensitive neurons are dominantly located (baro‐NTS), mean arterial pressure (MAP) and heart rate (HR) were significantly elevated. When tested in the area where chemosensitive neurons are dominantly located (chemo‐NTS), however, MAP and HR were significantly decreased. Pretreatment with the non‐specific α‐AR antagonist phentolamine into the NTS inhibited the phenylephrine‐induced cardiovascular responses. In contrast, microinjection of the α2‐AR agonist clonidine into either the baro‐NTS or the chemo‐NTS decreased MAP and HR; they were also inhibited by the α2‐adrenergic antagonist yohimbine. Moreover, we immunohistochemically identified that cardiovascular responses induced by α1‐ARs may be mediated by NTS neurons while those induced by α2‐ARs may be mediated by astrocytes located in the barosensitive and chemosensitive areas of the NTS. These results suggest that both types of α‐AR expressed in the NTS may be involved in regulating cardiovascular homeostasis via modulation of input signals from baroreceptor and chemoreceptor afferents; however, cardiovascular responses produced by stimulation of α1‐ARs are strictly location specific within the NTS.
Design and Manufacture of a Morphing Structure for a Shape-Adaptive Supersonic Wind Tunnel Nozzle
Authors: Steeves Craig A. , Timpano Katherine H. , Maxwell Peter T. , Martinelli Luigi , Miles Richard B.
Published: March 2009

Aerospace vehicles with fixed geometry are designed to operate at a predetermined flight condition. Variation of the aerodynamic environment, such as during acceleration, climbing, or turning, from the design condition reduces the efficiency of the vehicle. It would be advantageous to be able to adapt the vehicle geometry to maintain efficient flight over a range of aerodynamic conditions. Morphing sandwich structures offer sufficient strength and stiffness to serve as aerodynamic surfaces, while providing the shape-changing authority to attain a range of surface profiles without additional joints or seals. As a demonstration of the morphing concept in a supersonic environment, this paper describes the construction and testing of a morphing nozzle for a supersonic wind tunnel, which has been designed to operate isentropically over a Mach range from 2.5 to 3.8. The nozzle has been installed and operated in this Mach number range and the experimental results are presented.
Shakedown Fatigue Limits for Materials With Minute Porosity
Authors: Tirosh Jehuda , Peles Sharon
Published: March 2009

The intention of this study is to predict the fatigue-safe long life behavior of elastoplastic porous materials subjected to zero-tension fluctuating load. It is assumed that the materials contain a dilute amount of voids (less than 5%) and obey Gurson’s model of plastic yielding. The question to be answered is what would be the highest allowable stress amplitude that a porous material can endure (the “endurance limit”) when undergoing an infinite number of loading/unloading cycles. To reach the answer we employ the two shakedown theorems: (a) Melan’s static shakedown theorem (“elastic shakedown”) for establishing the lower bound to fatigue limit and (b) Koiter’s kinematic shakedown theorem (“plastic shakedown”) for establishing its upper bound. The two bounds are formulated rigorously but solved with some numerical assistance, mainly due to the nonlinear pressure dependency of the material behavior and the complex description of the plastic flow near stress-free voids. Both bounds (“dual bounds”) are adjusted to capture Gurson-like porous materials with noninteractive voids. General residual stresses (either real or virtual) are presented in the analysis. They are assumed to be time-independent as generated, say, by permanent temperature gradient between void surfaces and remote material boundaries. Such a situation is common, for instance, in ordinary porous sleeves (used in space industry and alike). A few experiments agree satisfactorily with the shakedown bounding concept.
Simulation of Moment Lyapunov Exponents for Linear Homogeneous Stochastic Systems
Authors: Xie Wei-Chau , Huang Qinghua
Published: March 2009

Moment Lyapunov exponents are important characteristic numbers for describing the dynamic stability of a stochastic system. When the pth moment Lyapunov exponent is negative, the pth moment of the solution of the stochastic system is stable. Monte Carlo simulation approaches complement approximate analytical methods in the determination of moment Lyapunov exponents and provides criteria on assessing the accuracy of approximate analytical results. For stochastic dynamical systems described by Itô stochastic differential equations, the solutions are diffusion processes and their variances may increase with time. Due to the large variances of the solutions and round-off errors, bias errors in the simulation of moment Lyapunov exponents are significant in improper numerical algorithms. An improved algorithm for simulating the moment Lyapunov exponents of linear homogeneous stochastic systems is presented in this paper.
Marginal Instability and Intermittency in Stochastic Systems—Part II: Systems With Rapid Random Variations in Parameters
Authors: Dimentberg M. F. , Hera A. , Naess A.
Published: March 2009

Dynamic systems with lumped parameters, which experience random temporal variations, are considered. The variations “smear” the boundary between the system’s states, which are dynamically stable and unstable in the classical sense. The system’s response within such a “twilight zone” of marginal instability is found to be of an intermittent nature, with alternating periods of zero (or almost-zero) response and rare short outbreaks. As long as it may be impractical to preclude completely such outbreaks for a designed system, subject to highly uncertain dynamic loads, the corresponding system’s response should be analyzed. Results of such analyses are presented for cases of slow and rapid (broadband) parameter variations in Papers I and II, respectively. The former case has been studied in Paper I (2008, “Marginal Instability and Intermittency in Stochastic Systems—Part I: Systems With Slow Random Variations of Parameters,” ASME J. Appl. Mech., 75(4), pp. 041002) for a linear model of the system using a parabolic approximation for the variations in the vicinity of their peaks (so-called Slepian model) together with Krylov–Bogoliubov averaging for the transient response. This resulted in a solution for the probability density function (PDF) of the response, which was of an intermittent nature indeed due to the specific algorithm of its generation. In the present paper (Paper II), rapid broadband parameter variations are considered, which can be described by the theory of Markov processes. The system is assumed to operate beyond its stochastic instability threshold—although only slightly—and its nonlinear model is used accordingly. The analysis is based on the solution of the Fokker–Planck–Kolmogorov partial differential equation for the relevant stationary PDF of the response. Several such PDFs are analyzed; they are found to have integrable singularities at the origin, indicating an intermittent nature of the response. Asymptotic analysis is performed for the first-passage problem for such response processes with highly singular PDFs, resulting in explicit formulas for an expected time interval between outbreaks in the intermittent response.
Local DNA Topography Correlates with Functional Noncoding Regions of the Human Genome
Authors: Parker Stephen C. J. , Hansen Loren , Abaan Hatice Ozel , Tullius Thomas D. , Margulies Elliott H.
Published: March 2009

The three-dimensional molecular structure of DNA, specifically the shape of the backbone and grooves of genomic DNA, can be dramatically affected by nucleotide changes, which can cause differences in protein-binding affinity and phenotype. We developed an algorithm to measure constraint on the basis of similarity of DNA topography among multiple species, using hydroxyl radical cleavage patterns to interrogate the solvent-accessible surface area of DNA. This algorithm found that 12% of bases in the human genome are evolutionarily constrained—double the number detected by nucleotide sequence–based algorithms. Topography-informed constrained regions correlated with functional noncoding elements, including enhancers, better than did regions identified solely on the basis of nucleotide sequence. These results support the idea that the molecular shape of DNA is under selection and can identify evolutionary history.
In Vivo Analysis of Dendritic Cell Development and Homeostasis
Authors: Liu Kang , Victora Gabriel D. , Schwickert Tanja A. , Guermonprez Pierre , Meredith Matthew M. , Yao Kaihui , Chu Fei-Fan , Randolph Gwendalyn J. , Rudensky Alexander Y. , Nussenzweig Michel
Published: March 2009

Dendritic cells (DCs) in lymphoid tissue arise from precursors that also produce monocytes and plasmacytoid DCs (pDCs). Where DC and monocyte lineage commitment occurs and the nature of the DC precursor that migrates from the bone marrow to peripheral lymphoid organs are unknown. We show that DC development progresses from the macrophage and DC precursor to common DC precursors that give rise to pDCs and classical spleen DCs (cDCs), but not monocytes, and finally to committed precursors of cDCs (pre-cDCs). Pre-cDCs enter lymph nodes through and migrate along high endothelial venules and later disperse and integrate into the DC network. Further cDC development involves cell division, which is controlled in part by regulatory T cells and fms-like tyrosine kinase receptor-3.
High Sensitivity and Specificity of Acid-Fast Microscopy for Diagnosis of Pulmonary Tuberculosis in an African Population with a High Prevalence of Human Immunodeficiency Virus
Authors: Shea Yvonne R. , Davis J. Lucian , Huang Laurence , Kovacs Joseph A. , Masur Henry , Mulindwa Francis , Opus Sally , Chow Yuenwah , Murray Patrick R.
Published: March 2009

Laboratories in low-income countries report that acid-fast microscopy is insensitive and nonspecific. We demonstrate that for a Ugandan population with high prevalences of tuberculosis and human immunodeficiency virus infection, acid-fast microscopy is highly sensitive (93.1%) and specific (100%) when performed by trained technologists in a carefully controlled manner using established techniques.
Impact of Discrepancies between the Abbott RealTime and Cobas TaqMan Assays for Quantification of Human Immunodeficiency Virus Type 1 Group M Non-B Subtypes
Authors: Wirden M. , Tubiana R. , Marguet F. , Leroy I. , Simon A. , Bonmarchand M. , Ait-Arkoub Z. , Murphy R. , Marcelin A. G. , Katlama C. , Calvez V.
Published: March 2009

Viral loads in 249 clinical samples from individual patients infected with human immunodeficiency virus type 1 non-B subtypes were determined with both the Abbott RealTime and Cobas TaqMan assays. The differences exceeded 0.5 log for about 20% of samples and 1 log for 3%, with higher values always from the Abbott assay in the latter cases.
A Common Variant of Staphylococcal Cassette Chromosome
mec
Type IVa in Isolates from Copenhagen, Denmark, Is Not Detected by the BD GeneOhm Methicillin-Resistant
Staphylococcus aureus
Assay
Authors: Bartels Mette Damkjaer , Boye Kit , Rohde Susanne Mie , Larsen Anders Rhod , Torfs Herbert , Bouchy Peggy , Skov Robert , Westh Henrik
Published: March 2009

Rapid tests for detection of methicillin-resistant
Staphylococcus aureus
(MRSA) carriage are important to limit the transmission of MRSA in the health care setting. We evaluated the performance of the BD GeneOhm MRSA real-time PCR assay using a diverse collection of MRSA isolates, mainly from Copenhagen, Denmark, but also including international isolates, e.g., USA100-1100. Pure cultures of 349 MRSA isolates representing variants of staphylococcal cassette chromosome
mec
(SCC
mec
) types I to V and 103 different staphylococcal protein A (
spa
) types were tested. In addition, 53 methicillin-susceptible
Staphylococcus aureus
isolates were included as negative controls. Forty-four MRSA isolates were undetectable; of these, 95% harbored SCC
mec
type IVa, and these included the most-common clone in Copenhagen,
spa
t024-sequence type 8-IVa. The false-negative MRSA isolates were tested with new primers (analyte-specific reagent [ASR] BD GeneOhm MRSA assay) supplied by Becton Dickinson (BD). The ASR BD GeneOhm MRSA assay detected 42 of the 44 isolates that were false negative in the BD GeneOhm MRSA assay. Combining the BD GeneOhm MRSA assay with the ASR BD GeneOhm MRSA assay greatly improved the results, with only two MRSA isolates being false negative. The BD GeneOhm MRSA assay alone is not adequate for MRSA detection in Copenhagen, Denmark, as more than one-third of our MRSA isolates would not be detected. We recommend that the BD GeneOhm MRSA assay be evaluated against the local MRSA diversity before being established as a standard assay, and due to the constant evolution of SCC
mec
cassettes, a continuous global surveillance is advisable in order to update the assay as necessary.
Characterization of a Novel Golgi Apparatus-Localized Latency Determinant Encoded by Human Cytomegalovirus
Authors: Petrucelli Alex , Rak Michael , Grainger Lora , Goodrum Felicia
Published: March 2009

Human cytomegalovirus (HCMV) exists indefinitely in infected individuals by a yet poorly characterized latent infection in hematopoietic cells. We previously demonstrated a requirement for the putativeUL138open reading frame (ORF) in promoting a latent infection in CD34+hematopoietic progenitor cells (HPCs) infected in vitro. In our present study, we have identified two coterminal transcripts of 2.7 and 3.6 kb and a 21-kilodalton (kDa) protein (pUL138) that are derived from theUL138locus with early-late gene kinetics during productive infection. TheUL138transcripts and protein are detected in both fibroblasts and HPCs. A recombinant virus, FIX-UL138STOP, that synthesizes theUL138transcripts but not the protein exhibited a partial loss-of-latency phenotype in HPCs, similar to the phenotype observed for theUL138-null recombinant virus. This finding suggests that the UL138 protein is required for latency, but it does not exclude the possibility that theUL138transcripts or other ORFs also contribute to latency. The mechanisms by which pUL138 contributes to latency remain unknown. While the 86- and 72-kDa immediate-early proteins were not detected in HPCs infected with HCMV in vitro, pUL138 did not function directly to suppress expression from the major immediate-early promoter in reporter assays. Interestingly, pUL138 localizes to the Golgi apparatus in infected cells but is not incorporated into virus particles. The localization of pUL138 to the Golgi apparatus suggests that pUL138 contributes to HCMV latency by a novel mechanism. pUL138 is the first HCMV protein demonstrated to promote an infection with the hallmarks of latency in CD34+HPCs.
Probing the Transcription Mechanisms of Reovirus Cores with Molecules That Alter RNA Duplex Stability
Authors: Demidenko Alexander A. , Nibert Max L.
Published: March 2009

The mammalian reovirus (MRV) genome comprises 10 double-stranded RNA (dsRNA) segments, packaged along with transcriptase complexes inside each core particle. Effects of four small molecules on transcription by MRV cores were studied for this report, chosen for their known capacities to alter RNA duplex stability. Spermidine and spermine, which enhance duplex stability, inhibited transcription, whereas dimethyl sulfoxide and trimethylglycine, which attenuate duplex stability, stimulated transcription. Different mechanisms were identified for inhibition or activation by these molecules. With spermidine, one round of transcription occurred normally, but subsequent rounds were inhibited. Thus, inhibition occurred at the transition between the end of elongation in one round and initiation in the next round of transcription. Dimethyl sulfoxide or trimethylglycine, on the other hand, had no effect on transcription by a constitutively active fraction of cores in each preparation but activated transcription in another fraction that was otherwise silent for the production of elongated transcripts. Activation of this other fraction occurred at the transition between transcript initiation and elongation, i.e., at promoter escape. These results suggest that the relative stability of RNA duplexes is most important for certain steps in the particle-associated transcription cycles of dsRNA viruses and that small molecules are useful tools for probing these and probably other steps.
The Respiratory Syncytial Virus Matrix Protein Possesses a Crm1-Mediated Nuclear Export Mechanism
Authors: Ghildyal Reena , Ho Adeline , Dias Manisha , Soegiyono Lydia , Bardin Phillip G. , Tran Kim C. , Teng Michael N. , Jans David A.
Published: March 2009

The respiratory syncytial virus (RSV) matrix (M) protein is localized in the nucleus of infected cells early in infection but is mostly cytoplasmic late in infection. We have previously shown that M localizes in the nucleus through the action of the importin β1 nuclear import receptor. Here, we establish for the first time that M's ability to shuttle to the cytoplasm is due to the action of the nuclear export receptor Crm1, as shown in infected cells, and in cells transfected to express green fluorescent protein (GFP)-M fusion proteins. Specific inhibition of Crm1-mediated nuclear export by leptomycin B increased M nuclear accumulation. Analysis of truncated and point-mutated M derivatives indicated that Crm1-dependent nuclear export of M is attributable to a nuclear export signal (NES) within residues 194 to 206. Importantly, inhibition of M nuclear export resulted in reduced virus production, and a recombinant RSV carrying a mutated NES could not be rescued by reverse genetics. That this is likely to be due to the inability of a nuclear export deficient M to localize to regions of virus assembly is indicated by the fact that a nuclear-export-deficient GFP-M fails to localize to regions of virus assembly when expressed in cells infected with wild-type RSV. Together, our data suggest that Crm1-dependent nuclear export of M is central to RSV infection, representing the first report of such a mechanism for a paramyxovirus M protein and with important implications for related paramyxoviruses.