bluuebunny/crossref_metadata_2025 huggingface dataset:
HIF-1α expression follows microvascular loss in advanced murine adriamycin nephrosis
Authors: Kairaitis Lukas Karolis , Wang Yiping , Gassmann Max , Tay Yuet-Ching , Harris David Charles Hamlyn
Published: September 2004

Cellular hypoxia has been proposed as a major factor in the pathogenesis of chronic renal injury, yet to date there has been no direct evidence to support its importance. Therefore, we examined cortical hypoxia in an animal model of chronic renal injury (murine adriamycin nephrosis; AN) by assessing nuclear localization of the oxygen-dependent α-subunit of hypoxia-inducible factor-1 (HIF-1α) in animals 7, 14, and 28 days after adriamycin. Results were assessed in conjunction with quantitation of the cortical microvasculature (by CD34 immunostaining) and cortical expression of VEGF. Cortical apoptosis was also examined by terminal deoxynucleotidyl transferase dUTP nick-end labeling staining. A dramatic and significant increase in nuclear localization of HIF-1α was seen 28 days after adriamycin in the context of severe glomerular and tubulointerstitial damage. Areas of nuclear HIF-1α staining did not colocalize with areas of cellular apoptosis. AN was also associated with a significant attenuation of the peritubular capillaries that was significant at 14 and 28 days after adriamycin. Cortical VEGF expression fell in a stepwise manner from day 7 until day 28 after adriamycin. In conclusion, these data are consistent with a significant increase in cellular hypoxia occurring in the advanced stages of murine AN. Increased cortical hypoxia was preceded by significant reductions in both the number of peritubular capillaries (i.e., oxygen supply) and the angiogenic cytokine VEGF. Apart from providing the first direct evidence for cellular hypoxia in a model of chronic renal disease, these results suggest that a primary dysregulation of angiogenesis may be the cause of increased hypoxia in this model.
Derivation of a new formula for calculating urinary electrolyte-free water clearance based on the Edelman equation
Authors: Nguyen Minhtri K. , Kurtz Ira
Published: September 2004

In evaluating the renal mechanisms responsible for the generation of the dysnatremias, an analysis of free water clearance (FWC) and electrolyte-free water clearance (EFWC) is often utilized to characterize the rate of urinary free water excretion in these disorders. Previous analyses of FWC and EFWC have failed to consider the relationship among plasma water Na+ concentration ([Na+]pw), total exchangeable Na+ (Nae), total exchangeable K+ (Ke), and total body water (TBW); (Edelman IS, Leibman J, O'Meara MP, and Birkenfeld LW. J Clin Invest 37: 1236–1256, 1958). In their derivations, the classic FWC and EFWC formulas fail to consider the quantitative and physiological significance of the slope and y-intercept in this equation. Consequently, previous EFWC formulas incorrectly assume that urine is isonatric when [Na+ + K+]urine = [Na+]p or [Na+ + K+]urine = [Na+]p + [K+]p (where [Na+]p and [K+]p represent plasma Na+ and K+ concentrations, respectively). Moreover, previous formulas cannot be utilized in the setting of hyperglycemia. In this article, we have derived a new formula termed modified electrolyte-free water clearance (MEFWC) for determining the electrolyte-free water clearance, taking into consideration the empirical relationship between the [Na+]pw and Nae, Ke, and TBW: MEFWC = V [1 − 1.03[Na+ + K+]urine/([Na+]p + 23.8)]. MEFWC, unlike previous formulas, is derived based on the requirement of the Edelman equation that urine is isonatric only when [Na+ + K+]urine = (Nae + Ke)/TBW = 0.97[Na+]p + 23.1. Furthermore, since we have shown that the y-intercept in the Edelman equation varies directly with the plasma glucose concentration, in patients with hyperglycemia, MEFWC = V [1 − 1.03[Na+ + K+]urine/{[Na+]p + 23.8 + (1.6/100)([glucose]p − 120)}]. The MEFWC formula will be especially useful in assessing the renal contribution to the generation of the dysnatremias.
A novel type of urea transporter, UT-C, is highly expressed in proximal tubule of seawater eel kidney
Authors: Mistry Abinash Chandra , Chen Guangping , Kato Akira , Nag Kakon , Sands Jeff M. , Hirose Shigehisa
Published: September 2004

A new type of urea transporter was identified by a database search and shown to be highly expressed in the renal proximal tubule cells of teleosts; proximal tubule-type urea transporters have not been describe previously. We first identified urea transporter-like sequences in the fugu genome and in an EST database of rainbow trout. Based on these pieces of sequence information, we obtained a full-length cDNA for the eel ortholog, consisting of 378 amino acid residues, and named it eUT-C. Although its sequence similarity to the known urea transporters is low (∼35%), its heterologous expression in Xenopus laevis oocytes indicated that it is a facilitative urea transporter sensitive to phloretin. Its activity is not dependent on Na+. Northern blot analysis showed that expression of eUT-C is highly restricted to the kidney, with weak expression in the stomach. In both tissues, eUT-C mRNA was strongly induced when eels were transferred from freshwater to seawater. Immunohistochemistry and in situ hybridization histochemistry revealed proximal tubule cell localization of eUT-C. Taking into account that 1) urea is mainly secreted from the gill where another type of urea transporter (eUT) has been identified and 2) fish excrete a very small volume of urine in seawater, we propose that eUT-C cloned here is a key component working in combination with the gill transporter to achieve an efficient urea excretory system in fish, namely, eUT-C reabsorbs urea from glomerular filtrate and sends it to the gill, through the circulation, for excretion.
Noninvasive measurement of temperature and fractional dissociation of imidazole in human lower leg muscles using 1H-nuclear magnetic resonance spectroscopy
Authors: Yoshioka Yoshichika , Oikawa Hiroshi , Ehara Shigeru , Inoue Takashi , Ogawa Akira , Kanbara Yoshiyuki , Kubokawa Manabu
Published: September 2004

The temperature change of the fractional dissociation of imidazole (α-imidazole) in resting human lower leg muscles was measured noninvasively using 1H-nuclear magnetic resonance spectroscopy at 3.0 and 1.5 T on five normal male volunteers aged 30.6 ± 10.4 yr (mean ± SD). Using 1H-nuclear magnetic resonance spectroscopy, water, carnosine, and creatine in the muscles could be simultaneously analyzed. Carnosine contains imidazole protons. The chemical shifts of water and carnosine imidazole protons relative to creatine could be used for estimating temperatures and α-imidazole, respectively. Using the chemical shift, the values of temperature in gastrocnemius (Gast) and soleus muscles at ambient temperature (21–25°C) were estimated to be 35.5 ± 0.5 and 37.4 ± 0.6°C (means ± SE), respectively (significantly different; P < 0.01). The estimated values of α-imidazole in these muscles were 0.620 ± 0.007 and 0.630 ± 0.013 (means ± SE), respectively (not significant). Alternation of the surface temperature of the lower leg from 40 to 10°C significantly changed the temperature in Gast ( P < 0.0001) from 38.1 ± 0.5 to 28.0 ± 1.2°C, and the α-imidazole in Gast decreased from 0.631 ± 0.003 to 0.580 ± 0.011 ( P < 0.05). However, the values of α-imidazole and the temperature in soleus muscles were not significantly affected by this maneuver. These results indicate that the α-imidazole in Gast changed significantly with alternation in muscle temperature ( r = 0.877, P < 0.00001), and its change was estimated to be 0.0058/°C.
Suppression of viral specific primary T-cell response following intense physical exercise in young but not old mice
Authors: Kapasi Zoher F. , McRae Michael L. , Ahmed Rafi
Published: September 2004

Intense exercise to exhaustion leads to increased susceptibility and severity of infections. T cells play an essential role in control of viral infections. Whereas immune suppression is considered as a likely mechanism for exhaustive exercise-induced susceptibility to infection, we know little about viral-specific T-cell response following exhaustive exercise in young or old mice. In this study, one group of female young (10–12 wk) and old (22–24 mo) C57BL/6 mice was exposed to a single bout of intense exercise to exhaustion and immediately infected with lymphocytic choriomeningitis virus (LCMV). Eight days later, at the peak of expansion phase of T-cell response, we used tetramers of MHC class I molecules containing viral peptides to directly visualize antigen-specific CD8 T cells and a sensitive functional assay measuring interferon-γ production at the single-cell level to quantitate the CD8 and CD4 T-cell response. To evaluate the impact of intense exercise during both the initiation and evolution of the expansion phase of the T-cell response, a second group of young and old mice continued their daily bouts of intense exercise to exhaustion over the next 8 days. Our data show that, in young mice, LCMV infection following exhaustive exercise leads to suppression of LCMV-specific CD8 and CD4 T-cell responses, and this suppression effect occurs at the initiation of the expansion phase of viral-specific T cells. However, in old mice, unlike young mice, exhaustive exercise does not cause suppression of LCMV-specific T-cell responses.
Mechanical interactions between collagen and proteoglycans: implications for the stability of lung tissue
Authors: Cavalcante Francisco S. A. , Ito Satoru , Brewer Kelly , Sakai Hiroaki , Alencar Adriano M. , Almeida Murilo P. , Andrade José S. , Majumdar Arnab , Ingenito Edward P. , Suki Béla
Published: September 2004

Collagen and elastin are thought to dominate the elasticity of the connective tissue including lung parenchyma. The glycosaminoglycans on the proteoglycans may also play a role because osmolarity of interstitial fluid can alter the repulsive forces on the negatively charged glycosaminoglycans, allowing them to collapse or inflate, which can affect the stretching and folding pattern of the fibers. Hence, we hypothesized that the elasticity of lung tissue arises primarily from 1) the topology of the collagen-elastin network and 2) the mechanical interaction between proteoglycans and fibers. We measured the quasi-static, uniaxial stress-strain curves of lung tissue sheets in hypotonic, normal, and hypertonic solutions. We found that the stress-strain curve was sensitive to osmolarity, but this sensitivity decreased after proteoglycan digestion. Images of immunofluorescently labeled collagen networks showed that the fibers follow the alveolar walls that form a hexagonal-like structure. Despite the large heterogeneity, the aspect ratio of the hexagons at 30% uniaxial strain increased linearly with osmolarity. We developed a two-dimensional hexagonal network model of the alveolar structure incorporating the mechanical properties of the collagen-elastin fibers and their interaction with proteoglycans. The model accounted for the stress-strain curves observed under all experimental conditions. The model also predicted how aspect ratio changed with osmolarity and strain, which allowed us to estimate the Young's modulus of a single alveolar wall and a collagen fiber. We therefore identify a novel and important role for the proteoglycans: they stabilize the collagen-elastin network of connective tissues and contribute to lung elasticity and alveolar stability at low to medium lung volumes.
Genetic influence on daily wheel running activity level
Authors: Lightfoot J. Timothy , Turner Michael J. , Daves Meredith , Vordermark Anna , Kleeberger Steven R.
Published: September 2004

This project was designed to determine the genetic (between-strain) and environmental (within-strain) variance in daily running wheel activity level in inbred mice. Five male and five female mice, 9.7–15.3 wk old, from each of 13 strains (A/J, AKR/J, BALB/cJ, C3H/HeJ, C57Bl/6J, C57L/J, C3Heb/FeJ, CBA/J, DBA/2J, SWR/J, MRL/MpJ, SPRET/Ei, and CAST/Ei) as well as five female NZB/BinJ mice were housed individually. A running wheel in each cage was interfaced with a magnetic sensor to measure total daily distance and exercise time for each animal every 24 h for 21 consecutive days (3 wk). Average daily distance (km), duration (min), and velocity (m/min) for each strain was then calculated. Significant interstrain differences in average daily distance ( P < 0.001), average daily exercise duration ( P < 0.0001), and average daily exercise velocity ( P < 0.0001) were found, with C57L/J mice running farther and faster than the other strains. Sex was a significant factor in daily running wheel activity, with female mice running an average of 20% farther ( P = 0.01) and 38% faster ( P < 0.0001) than male mice. The male mice ran 15% longer duration on a daily basis ( P = 0.0091). Weight was only associated with exercise velocity in the female mice, but this relationship was not significant when subdivided by strain. Broad-sense heritability estimates on the physical activity differed by sex (for distance, male 31–48% and female 12–22%; for duration, male 44–61% and female 12–21%; for velocity, male 49–66% and female 44–61%). In conclusion, these data indicate that daily running wheel activity level in mice is significantly affected by genetic background and sex.
The equivalence of Mann iteration and Ishikawa iteration for ψ‐uniformly pseudocontractive or ψ‐uniformly accretive maps
Authors: Rhoades B. E. , Şoltuz Ştefan M.
Published: September 2004

We show that the Ishikawa iteration and the corresponding Mann
iteration are equivalent when applied to ψ‐uniformly
pseudocontractive or ψ‐uniformly accretive maps.
The 3D Happel model for complete isotropic Stokes flow
Authors: Dassios George , Vafeas Panayiotis
Published: September 2004

The creeping flow through a swarm of spherical particles that
move with constant velocity in an arbitrary direction and rotate
with an arbitrary constant angular velocity in a quiescent
Newtonian fluid is analyzed with a 3D sphere‐in‐cell model. The
mathematical treatment is based on the two‐concentric‐spheres
model. The inner sphere comprises one of the particles in the
swarm and the outer sphere consists of a fluid envelope. The
appropriate boundary conditions of this non‐axisymmetric
formulation are similar to those of the 2D sphere‐in‐cell Happel
model, namely, nonslip flow condition on the surface of the solid
sphere and nil normal velocity component and shear stress on the
external spherical surface. The boundary value problem is solved
with the aim of the complete Papkovich‐Neuber differential
representation of the solutions for Stokes flow, which is valid
in non‐axisymmetric geometries and provides us with the velocity
and total pressure fields in terms of harmonic spherical
eigenfunctions. The solution of this 3D model, which is
self‐sufficient in mechanical energy, is obtained in closed form
and analytical expressions for the velocity, the total pressure,
the angular velocity, and the stress tensor fields are provided.
Toy quantum mechanics using hidden variables
Authors: Kurakin Pavel V. , Malinetskii George G.
Published: September 2004

An original model of toy quantum mechanics that uses hidden
variables but does not violate the well‐known Bell theorem is
proposed.
Acceleration of Runge‐Kutta integration schemes
Authors: Phohomsiri Phailaung , Udwadia Firdaus E.
Published: September 2004

A simple accelerated third‐order Runge‐Kutta‐type, fixed time
step, integration scheme that uses just two function evaluations
per step is developed. Because of the lower number of function
evaluations, the scheme proposed herein has a lower computational
cost than the standard third‐order Runge‐Kutta scheme while
maintaining the same order of local accuracy. Numerical examples
illustrating the computational efficiency and accuracy are
presented and the actual speedup when the accelerated algorithm
is implemented is also provided.
Nonlinear Volterra difference equations in space lp
Authors: Gil′ Michael I. , Medina Rigoberto
Published: September 2004

We consider a class of vector nonlinear discrete‐time Volterra
equations in space lp and derive estimates for the norms of
solutions. These estimates give us explicit stability conditions,
which allow us to avoid finding Lyapunov functionals.
Camera Lucida: A Three-Dimensional Sonochemical Observatory
Authors: Domnitch Evelina , Gelfand Dmitry
Published: September 2004

Camera Lucida is an interactive “sonic observatory” that directly converts sound waves into light by employing a phenomenon called sonoluminescence. The project was conceived both as an artwork and as a musical instrument that allows its player to see and shape sounds while moving through space.
Toward a Diffracted Literature
Authors: Balpe Jean-Pierre
Published: September 2004

Over a relatively short period of its history, literature has become closely linked to the book; but literature preceded the book, and today its creation, due to its digital form, is more and more linked to screens or to sound output interfaces. Because the screen is not a material object but a virtual one, it can take as many forms as its users wish. This article attempts, first by means of an excerpted short story by the author and then in a theoretical discussion, to demonstrate and analyze some of the implications of the use of the screen in the field of e-literature.
Miniaturization and the Opening of The Mouth in a Greek Magical Text (Pgm Xii.270-350)
Authors: Moyer Ian , Dieleman Jacco
Published: September 2004

PGM XII.270-350, a text prescribing rituals for the creation and use of a magical ring, provides a particularly useful example through which to explore the phenomenon of miniaturized ritual in the magical papyri of late Graeco-Roman Egypt (as elucidated by Smith 1995). The ritual for creating and consecrating the ring's gemstone makes it clear that the stone is considered a miniature cult statue. The subsequent "Ouphor" invocation to be performed whenever the ring is used corresponds in name and function to the Egyptian wp. t-r or Opening the Mouth ritual as used in daily temple liturgy. The nature of these ritual miniatures reveals the sophisticated discursive and conceptual level at which the traditional forms of temple ritual were adapted and redeployed for use in other contexts by members of the Egyptian priestly class in late antiquity.
Dominancia social y neosexismo: relación con las actitudes hacia programas de acción afirmativa
Authors: Montes-Berges Beatriz , Silván-Ferrero Ma del Prado
Published: September 2004

El neosexismo, definido como la manifestación de un conflicto entre los valores igualitarios y los sentimientos residuales negativos hacia las mujeres (Tougas, Brown, Beaton y Joli, 1995), se ha relacionado tradicionalmente con las actitudes hacia los programas de acción afirmativa y con los sentimientos de amenaza hacia los intereses colectivos (Montes-Berges, 2002; Moya y Expósito, 2001). Recientes estudios han relacionado el neosexismo con la tendencia a la dominancia social (Pratto, Sidanius, Stallworth y Malle, 1994). El objetivo de este trabajo es estudiar la relación entre la tendencia a la dominancia social, el neoseximo, los sentimientos de amenaza hacia los intereses colectivos de los varones y las actitudes hacia los programas de acción afirmativa. La muestra estaba formada por 86 participantes, 39 hombres y 47 mujeres. Los resultados obtenidos se interpretan a la luz de las publicaciones más recientes sobre el tema.
Variables psicosociales como predictoras de la salud en mujeres
Authors: Landero René , González Mónica-Teresa
Published: September 2004

El presente estudio propone un modelo predictivo del estado de salud (físico y mental) de las mujeres. Para lograr lo anterior, se analiza la relación entre las variables psicosociales y el estrés. Además se utiliza la Regresión Múltiple para detectar las variables que predicen el estado de salud percibido de las mujeres de la muestra incidental del estudio (n = 283). Se encontró que para la salud física la varianza explicada por las variables psicosociales fue del 27%, y para la salud mental, el 47% de la varianza. En ambos modelos el estrés fue la variable principal.
Educando a los hijos para ser padres
Authors: Torres Laura-Evelia , Ortega Patricia , Garrido Adriana
Published: September 2004

En México el papel que tradicionalmente desempeñaban hombres y mujeres dentro de la familia ha cambiado. Estos cambios se han atribuido a políticas gubernamentales, educativas, sociales y, en gran medida, a la inserción femenina en el ámbito laboral. Entre estos cambios se encuentra una mayor participación de los varones en la crianza de sus hijos, a diferencia de la que efectuaron sus padres. Sin embargo, el contacto con la paternidad de sus padres les ha servido como referencia para ejercer la paternidad. En este trabajo estudiamos tres aspectos relacionados con la paternidad en un grupo de 28 varones mexicanos: su vivencia como hijos con la paternidad de sus padres, su preparación para la crianza, y la relación que perciben entre su paternidad y la de sus padres. Encontramos que la vivencia de los varones con sus padres les ha permitido construir un modelo propio, tomando como base el modelo de sus padres, ya sea para reproducirlo, cambiarlo o transformarlo. Se discute la deficiente educación para la paternidad que existe en los varones y se expone la necesidad de políticas sociales que les auxilien en la práctica de su paternidad.
Formación de adolescentes en donación y trasplante de órganos
Authors: Blanca María-J. , Frutos Miguel-A. , Rando Belén , Ruiz Pilar
Published: September 2004

El presente trabajo pretende evaluar, en estudiantes adolescentes, la efectividad de un programa informativo sobre el proceso de donación-extracción-trasplante con el objetivo de aumentar los conocimientos sobre el tema, promover una reflexión personal que propicie actitudes y decisiones positivas respecto a la donación, y promover la discusión con los familiares más cercanos. Para ello, se hizo partícipe a los profesores y orientadores de los centros, quienes recibieron un curso formativo sobre donación y trasplante de órganos y tejidos, para posteriormente ser la fuente de información de sus alumnos mediante la impartición de dos seminarios a los mismos. El primero se centró en contenidos referentes a la prevención y tratamiento de enfermedades renales y el segundo a la donación y trasplante de órganos. En el estudio participaron 750 estudiantes y para la evaluación de la intervención se administró una encuesta antes y después de la misma. Los datos indican un aumento del conocimiento sobre el tema, un aumento en el número de sujetos que han dialogado con la familia y un incremento moderado del número de adolescentes dispuestos a donar sus propios órganos, aunque este cambio no se produce para los órganos de un familiar fallecido.
Combination therapy for adult T-cell leukemia–xenografted mice: flavopiridol and anti-CD25 monoclonal antibody
Authors: Zhang Meili , Zhang Zhuo , Goldman Carolyn K. , Janik John , Waldmann Thomas A.
Published: September 2004

Adult T-cell leukemia (ATL) develops in a small proportion of individuals infected with human T-cell lymphotrophic virus-1. The leukemia consists of an overabundance of activated T cells, which express CD25 on their cell surfaces. Presently, there is no accepted curative therapy for ATL. Flavopiridol, an inhibitor of cyclin-dependent kinases, has potent antiproliferative effects and antitumor activity. We investigated the therapeutic efficacy of flavopiridol alone and in combination with humanized anti-Tac antibody (HAT), which recognizes CD25, in a murine model of human ATL. The ATL model was established by intraperitoneal injection of MET-1 leukemic cells into nonobese diabetic/severe combined immunodeficient mice. Either flavopiridol, given 2.5 mg/kg body weight daily for 5 days, or HAT, given 100 μg weekly for 4 weeks, inhibited tumor growth as monitored by serum levels of human β-2-microglobulin (β2μ; P < .01), and prolonged survival of the leukemia-bearing mice (P < .05) as compared with the control group. Combination of the 2 agents dramatically enhanced the antitumor effect, as shown by both β2μ levels and survival of the mice, when compared with those in the flavopiridol or HAT alone group (P < .01). The significantly improved therapeutic efficacy by combining flavopiridol with HAT provides support for a clinical trial in the treatment of ATL.
Selective Rac1 inhibition in dendritic cells diminishes apoptotic cell uptake and cross-presentation in vivo
Authors: Kerksiek Kristen M. , Niedergang Florence , Chavrier Philippe , Busch Dirk H. , Brocker Thomas
Published: September 2004

To better understand the influence of cytoskeletal regulation on dendritic cell (DC) function in vivo, the Rho guanosine triphosphatase (GTPase) Rac1 was selectively inhibited in DCs in transgenic (Tg) mice. Although transgene expression did not interfere with the migratory capacities of DC in vivo, a decreased uptake of fluorescent probes was observed. Interestingly, the absence of full Rac1 function most strongly affected the development and function of CD8+ DCs. Apoptotic cell uptake was severely reduced in Tg mice, impairing subsequent DC-mediated cross-presentation and priming of bacteria-specific T-cell responses. These findings highlight a special role for Rac1 in the capacity of CD8+ DCs to endocytose apoptotic cells and prime T cells via cross-presentation.
FbsA, a fibrinogen-binding protein from Streptococcus agalactiae, mediates platelet aggregation
Authors: Pietrocola Giampiero , Schubert Axel , Visai Livia , Torti Mauro , Fitzgerald J. Ross , Foster Timothy J. , Reinscheid Dieter J. , Speziale Pietro
Published: September 2004

The bacterium Streptococcus agalactiae is an etiologic agent in the pathogenesis of endocarditis in humans. FbsA, a fibrinogen-binding protein produced by this pathogen, is considered an important virulence factor. In the present study we provide evidence that S agalactiae clinical isolates bearing FbsA attach to fibrinogen and elicit a fibrinogen-dependent aggregation of platelets. Mutants of S agalactiae lacking the fbsA gene lost the ability to attach to fibrinogen and to aggregate platelets. Plasmid-mediated expression of fbsA restored the capability for fibrinogen binding and platelet aggregation in S agalactiae fbsA mutants, and allowed Lactococcus lactis to interact with fibrinogen and to aggregate human platelets. Moreover, a monoclonal anti-FbsA antibody inhibited bacterial adherence to fibrinogen and S agalactiae–induced platelet aggregation. Platelet aggregation was inhibited by aspirin, prostaglandin E1, the peptide RGDS, and the antibody abciximab, demonstrating the specificity of platelet aggregation by S agalactiae and indicating an involvement of integrin glycoprotein IIb/IIIa in the induction of platelet aggregation. Aggregation was also dependent on anti-FbsA IgG and could be inhibited by an antibody against the platelet FcγRIIA receptor. These findings indicate that FbsA is a crucial factor in S agalactiae–induced platelet aggregation and may therefore play an important role in S agalactiae–induced endocarditis.
Relevance of sexual dimorphism to regulatory T cells: estradiol promotes IFN-γ production by invariant natural killer T cells
Authors: Gourdy Pierre , Araujo Luiza M. , Zhu Ren , Garmy-Susini Barbara , Diem Séverine , Laurell Henrik , Leite-de-Moraes Maria , Dy Michel , Arnal Jean François , Bayard Francis , Herbelin André
Published: September 2004

Mechanisms accounting for gender dimorphism during immune responses are still poorly understood. Since invariant natural killer T (iNKT) cells exert important regulatory functions through their capacity to produce both T helper 1 (Th1) and Th2 cytokines, we addressed the question of whether these activities could be modulated by sexual hormones. We found that in vivo challenge with the specific ligand of iNKT cells, α-galactosylceramide (α-GalCer), induced significantly higher concentrations of interferon γ (IFN-γ) in the serum of female than in that of male mice, while interleukin 4 (IL-4) production was not modified. In support of a crucial role of ovarian hormones in this phenomenon, a significant decrease of serum IFN-γ concentrations occurred in ovariectomized females, in response to treatment with α-GalCer, while orchidectomy affected neither IFN-γ nor IL-4 serum concentrations in males. The implication of estrogens in this selective enhancement of IFN-γ production by iNKT cells was demonstrated by (1) the increased α-GalCer–induced IFN-γ synthesis by iNKT cells upon both in vitro and in vivo exposure to estradiol and (2) the abolition of the sex-linked difference in α-GalCer–induced IFN-γ release in estrogen receptor α-deficient mice. These results provide the first evidence that estrogens influence iNKT cells leading to this gender dimorphism in their cytokine production profile.
PEDRo: A database for storing, searching and disseminating experimental proteomics data
Authors: Garwood Kevin , McLaughlin Thomas , Garwood Chris , Joens Scott , Morrison Norman , Taylor Christopher F , Carroll Kathleen , Evans Caroline , Whetton Anthony D , Hart Sarah , Stead David , Yin Zhikang , Brown Alistair JP , Hesketh Andrew , Chater Keith , Hansson Lena , Mewissen Muriel , Ghazal Peter , Howard Julie , Lilley Kathryn S , Gaskell Simon J , Brass Andy , Hubbard Simon J , Oliver Stephen G , Paton Norman W
Published: September 2004

Background

Proteomics is rapidly evolving into a high-throughput technology, in which substantial and systematic studies are conducted on samples from a wide range of physiological, developmental, or pathological conditions. Reference maps from 2D gels are widely circulated. However, there is, as yet, no formally accepted standard representation to support the sharing of proteomics data, and little systematic dissemination of comprehensive proteomic data sets.

Results

This paper describes the design, implementation and use of a P roteome E xperimental D ata R epo sitory (PEDRo), which makes comprehensive proteomics data sets available for browsing, searching and downloading. It is also serves to extend the debate on the level of detail at which proteomics data should be captured, the sorts of facilities that should be provided by proteome data management systems, and the techniques by which such facilities can be made available.

Conclusions

The PEDRo database provides access to a collection of comprehensive descriptions of experimental data sets in proteomics. Not only are these data sets interesting in and of themselves, they also provide a useful early validation of the PEDRo data model, which has served as a starting point for the ongoing standardisation activity through the Proteome Standards Initiative of the Human Proteome Organisation.
Activation of Erk and JNK MAPK pathways by acute swim stress in rat brain regions
Authors: Shen Chang-peng , Tsimberg Yelena , Salvadore Christopher , Meller Emanuel
Published: September 2004

Background

The mitogen-activated protein kinases (MAPKs) have been shown to participate in a wide array of cellular functions. A role for some MAPKs (e.g., extracellular signal-regulated kinase, Erk1/2) has been documented in response to certain physiological stimuli, such as ischemia, visceral pain and electroconvulsive shock. We recently demonstrated that restraint stress activates the Erk MAPK pathway, but not c-Jun-N-terminal kinase/stress-activated protein kinase (JNK/SAPK) or p38MAPK, in several rat brain regions. In the present study, we investigated the effects of a different stressor, acute forced swim stress, on the phosphorylation (P) state of these MAPKs in the hippocampus, neocortex, prefrontal cortex, amygdala and striatum. In addition, effects on the phosphorylation state of the upstream activators of the MAPKs, their respective MAPK kinases (MAPKKs; P-MEK1/2, P-MKK4 and P-MKK3/6), were determined. Finally, because the Erk pathway can activate c-AMP response element (CRE) binding (CREB) protein, and swim stress has recently been reported to enhance CREB phosphorylation, changes in P-CREB were also examined.

Results

A single 15 min session of forced swimming increased P-Erk2 levels 2–3-fold in the neocortex, prefrontal cortex and striatum, but not in the hippocampus or amygdala. P-JNK levels (P-JNK1 and/or P-JNK2/3) were increased in all brain regions about 2–5-fold, whereas P-p38MAPK levels remained essentially unchanged. Surprisingly, levels of the phosphorylated MAPKKs, P-MEK1/2 and P-MKK4 (activators of the Erk and JNK pathways, respectively) were increased in all five brain regions, and much more dramatically (P-MEK1/2, 4.5 to > 100-fold; P-MKK4, 12 to ~300-fold). Consistent with the lack of forced swim on phosphorylation of p38MAPK, there appeared to be no change in levels of its activator, P-MKK3/6. P-CREB was increased in all but cortical (prefrontal, neocortex) areas.

Conclusions

Swim stress specifically and markedly enhanced the phosphorylation of the MAPKKs P-MEK1/2 and P-MKK4 in all brain regions tested without apparent alteration in the phosphorylation of P-MKK3/6. Curiously, phosphorylation of their cognate substrates (Erk and JNK) was increased to a much more modest extent, and in some brain regions was not altered. Similarly, there was a region-specific discrepancy between Erk and CREB phosphorylation. Possible explanations for these findings and comparison with the effects of restraint stress will be discussed.
Suboptimal clinical response to ciprofloxacin in patients with enteric fever due to Salmonella spp. with reduced fluoroquinolone susceptibility: a case series
Authors: Slinger Robert , Desjardins Marc , McCarthy Anne E , Ramotar Karam , Jessamine Peter , Guibord Christiane , Toye Baldwin
Published: September 2004

Background

Salmonella spp. with reduced susceptibility to fluoroquinolones have higher than usual MICs to these agents but are still considered "susceptible" by NCCLS criteria. Delayed treatment response to fluoroquinolones has been noted, especially in cases of enteric fever due to such strains. We reviewed the ciprofloxacin susceptibility and clinical outcome of our recent enteric fever cases.

Methods

Salmonella enterica Serotype Typhi (S. Typhi) and Serotype Paratyphi (S. Paratyphi) blood culture isolates (1998–2002) were tested against nalidixic acid by disk diffusion (DD) and agar dilution (AD) and to ciprofloxacin by AD using NCCLS methods and interpretive criteria. Reduced fluoroquinolone susceptibility was defined as a ciprofloxacin MIC of 0.125–1.0 mg/L. The clinical records of patients treated with ciprofloxacin for isolates with reduced fluoroquinolone susceptibility were reviewed.

Results

Seven of 21 (33%) S. Typhi and S. Paratyphi isolates had reduced susceptibility to fluoroquinolones (MIC range 0.125–0.5 mg/L). All 7 were nalidixic acid resistant by DD (no zone) and by AD (MIC 128- >512 mg/L). The other 14 isolates were nalidixic acid susceptible and fully susceptible to ciprofloxacin (MIC range 0.015–0.03 mg/L).

Five of the 7 cases were treated initially with oral ciprofloxacin. One patient remained febrile on IV ciprofloxacin until cefotaxime was added, with fever recurrence when cefotaxime was discontinued. Two continued on oral or IV ciprofloxacin alone but had prolonged fevers of 9–10 days duration, one was switched to IV beta-lactam therapy after remaining febrile for 3 days on oral/IV ciprofloxacin and one was treated successfully with oral ciprofloxacin. Four of the 5 required hospitalization.

Conclusions

Our cases provide further evidence that reduced fluoroquinolone susceptibility of S. Typhi and S. Paratyphi is clinically significant. Laboratories should test extra-intestinal Salmonella spp. for reduced fluoroquinolone susceptibility.
Common carotid pseudoaneurysm after carotid endarterectomy: a case presentation
Authors: Grant April A , Gray Bruce H
Published: September 2004

A patient with a previous history of neck cancer and carotid endarterectomy presents with a pulsatile cervical mass. Further evaluation reveals the presence of a pseudoaneurysm of the common carotid artery. The endovascular treatment options and techniques employed to exclude the pseudoaneurysm are presented and discussed.
Efficient transfer of receptor-associated protein (RAP) across the blood-brain barrier
Authors: Pan Weihong , Kastin Abba J. , Zankel Todd C. , van Kerkhof Peter , Terasaki Tetsuya , Bu Guojun
Published: September 2004

We have sought to identify a high-capacity transport system that mediates transcytosis of proteins from the blood to the brain. The 39 kDa receptor-associated protein (RAP) functions as a specialized endoplasmic reticulum chaperone assisting in the folding and trafficking of members of the low-density lipoprotein (LDL) receptor family. RAP efficiently binds to these receptors and antagonizes binding of other ligands. Previous studies have shown that two large members of the LDL receptor family, LDL receptor-related protein 1 (LRP1) and LDL receptor-related protein 2 (LRP2 or megalin), possess the ability to mediate transcytosis of ligands across the brain capillary endothelium. Here, we tested whether blood-borne RAP crosses the blood-brain barrier (BBB) by LRP1- or megalin-mediated transport by studying the pharmacokinetics of [125I]-RAP transport into the brain in intact mice and across cell monolayers in vitro. Our results show that [125I]-RAP is relatively stable in blood for 30 minutes and has a mean influx constant of 0.62±0.08 μl/g-minute from blood to brain. In situ brain perfusion in blood-free buffer shows that transport of [125I]-RAP across the BBB is a saturable process. Capillary depletion of brain homogenates indicates that 70% of [125I]-RAP is localized in the parenchyma rather than in the vasculature of the brain. Results of transport in stably transfected MDCK cells are consistent with the hypothesis that megalin mediates most of the apical-to-basolateral transport across polarized epithelial cells. The inhibition of [125I]-RAP influx by excess RAP and the involvement of megalin indicate the presence of a saturable transport system at the BBB. The higher permeability of RAP compared with that of melanotransferrin and transferrin show that the LRP receptor is a high capacity transport system. These studies suggest that RAP may provide a novel means of protein-based drug delivery to the brain.
Analysis of brake assembly with floating disc
Authors: MacLennan L D
Published: September 2004

The task of specifying a brake system for a vehicle is without doubt one of the most crucial decisions a design manager must undertake in the development process of a vehicle. Improved vehicle aerodynamics, higher loads, more horsepower and increased road safety all create the need for more effective brake systems. The most dominant of these is the disc brake system, due to the absence of fade and the possibility of effectively modulating the brake force. The latter represents a broad area of on-going research in mechatronics in addition to the more traditional areas of mechanical research such as optimizing geometry, surface finish, material compositions and so forth. In recent years the development of brake systems with twin floating discs and a fixed caliper has been undertaken commercially. Due to the economical advantages and from considerations of space, the disc is preferably guided by the pads. In the initial process of the experimental research, a high drag torque was acquired without applying force to the pads. This phenomenon posed the question, treated here, as to whether the drag could be eliminated by alterations in the spline profile and disc geometry. A static analytical study is presented parallel to an experimental study. The spline profile and the nave width were proven to have little effect upon drag, while the position on which the caliper was mounted had a considerable influence. Both the analytical study and the experimental measurements showed a strong correlation between the caliper position and the drag torque.
Mass loss and blunting during high-speed penetration
Authors: Davis R N , Neely A M , Jones S E
Published: September 2004

A new analytical model of high-speed friction was developed to account for the observed velocity dependence in sliding friction at high speeds and was successfully applied to the analysis of data previously reported by Jones et al. for a number of concrete penetration tests using ogive-nose projectiles of high-strength steel alloy. The model permitted very consistent predictions of penetrator performance and target strength based on the experimental data. The subsequent development by Davis et al. of a stepwise incremental approximation to the velocity-dependent coefficient of sliding friction simplified the implementation of the model, while preserving the quality of the linear approximation to the assumed velocity dependence in sliding friction at high speeds. The stepwise function further led to an engineering model for mass loss, neglecting the effects of blunting, which successfully related the work done by friction to the mass loss due to surface melting of the nose.

In this paper, a generalized dimensionless nose equation is developed, allowing these results to be applied to geometries other than the ogival case. Furthermore, the effects of blunting and progressive mass loss from the nose are incorporated into the existing model of high-speed penetration and applied to the analysis of previously reported penetration data. By incorporating changing nose mass and geometry due to frictional wear, the performance characteristics of steel alloys and selected nose geometries can be better evaluated, and the processes governing high-speed penetration and mass loss better understood. Given penetrator material, impact velocity and target properties, it is also possible to predict the performance of various nose geometries.
Vibration analysis of rotors for the identification of shaft misalignment Part 2: Experimental validation
Authors: Saavedra P N , Ramírez D E
Published: September 2004

In Part 1 of this paper, a theoretical model to determine the dynamic behaviour of misaligned shaft rotors connected by a flexible coupling was developed. In this Part 2, experimental tests are performed to validate the model and simulation results obtained in Part 1. Vibratory characteristics, such as the frequency spectrum, waveform and phase shifts of the spectral components across the coupling are presented for different magnitudes of misalignment and types of coupling. Traditional vibration analysis rules used in practical predictive maintenance to diagnose shaft misalignment are evaluated. The influence of the frequency response functions on the amplitude of the spectral components and on the phase shifts of the spectral components across a coupling were studied. Finally, some practical conclusions for more reliable shaft misalignment identification using vibration analysis are suggested.
Chaos, chaos control and synchronization of the vibrometer system
Authors: Ge Z-M , Lin C-C , Chen Y-S
Published: September 2004

The dynamic system of the vibrometer is shown to produce regular and chaotic behaviour as the parameters are varied. When the system is non-autonomous, the periodic and chaotic motions are obtained by numerical methods. Many effective methods have been used in chaos synchronization. It has been shown that chaos can be synchronized using special feedback control and that external excitations affect the synchronization.
Hygrothermal stress analysis of a plastic ball grid array package during solder reflow
Authors: Chang K-C , Yeh M-K , Chiang K-N
Published: September 2004

This study investigated how the internal temperature and moisture of a plastic ball grid array (PBGA) package affect interfacial hygrothermal stresses (primarily peeling and shear stresses) during solder reflow. Two-dimensional finite element analysis was applied to evaluate temperature distribution, moisture diffusion and hygrothermal stresses inside the PBGA package. A series of popcorn experiments on PBGA packages was carried out to verify the accuracy of the finite element model. The design parameters of the PBGA package were varied to assess their effect on hygrothermal stresses at the interfaces. Moisture absorption and desorption experiments on the PBGA packaging materials were conducted in a hygrothermal chamber and an oven, to obtain moisture diffusivity data and saturated moisture contents of PBGA packaging materials. Results in this study can be applied to optimize the design parameters of the PBGA package and thus reduce interfacial hygrothermal stresses during solder reflow.
Biaxial ratcheting deformation of type 304 stainless steel: Effect of memorization of back stress
Authors: Mayama T , Sasaki K , Ishikawa H
Published: September 2004

This paper treats both experiments and simulations of biaxial ratcheting. The experiments are conducted using a tubular specimen of type 304 stainless steel at room temperature. The specimen was subjected to cyclic shear straining under the axial superposed stress. The experiments show that the biaxial ratcheting strain was affected by the cyclic shear strain amplitude, the shear strain rate and the superposed stress level. Larger biaxial ratcheting strain occurred in the case of tensile superposed stress compared with that in the case of the compressive superposed stress. Moreover, even under the zero superposed stress, biaxial ratcheting strain occurred in the axial direction due to the cyclic shearing straining. Finally, the biaxial ratcheting behaviours were simulated by the unified constitutive model proposed by the authors. The characteristic features of the biaxial ratcheting behaviour, especially the axial strain due to the cyclic shear straining superposed on the zero axial stress, are well simulated by the constitutive model.
Vibration analysis of rotors for the identification of shaft misalignment Part 1: Theoretical analysis
Authors: Saavedra P N , Ramírez D E
Published: September 2004

Shaft misalignment in machinery causes preload forces to be generated in couplings which are then transmitted to the different machine components, thus reducing their lifetime. Shaft misalignment is a major cause of vibration in machines. Based on tests on coupling stiffness, a new coupling finite element stiffness matrix has been deduced. This has been used in the finite element analysis of a two-rotor system connected by a flexible coupling, to calculate the mechanical vibration resulting from mixed angular and parallel shaft misalignments with residual unbalance. The calculated vibration spectra were determined for two flexible couplings: a three-pin Renold coupling and a three-jaw Lovejoy coupling. The results and analysis indicate that the vibration generated by shaft misalignment is caused by the variation in coupling stiffness on rotation, and that the forcing frequencies generated are harmonics of the shaft's speed and directly depend on the frequency of the variation in coupling stiffness. In addition, the amplitudes of the measured vibratory components were found to rely directly upon the frequency response function that is related to the coupling and measurement points.
Non-linear joint parameter identification using the frequency response function of the linear substructure
Authors: Kim W-J , Lee B-Y , Park Y-S
Published: September 2004

A method based on frequency domain approaches is presented for the non-linear parameter identification of a structure having non-linear joints. The frequency response function (FRF) of the linear substructure, which can be calculated from the finite element method or measured by an experimental method, is used to calculate its FRFs needed in the parameter identification process. This method is easily applicable to a complex real structure having non-linear joints since it uses the FRF of the substructure. Since this method is performed in the frequency domain, the number of equations can be easily increased to as many as required to identify unknown parameters, not only by just varying the excitation amplitude but also by selecting the excitation frequencies. The validity of this method was tested numerically and experimentally with a cantilever beam having a non-linear element. It was verified through examples that the proposed method is useful to identify the non-linear joint parameters of a structure having arbitrary boundaries.