bluuebunny/crossref_metadata_2025 huggingface dataset:
Neural Network Retrieval of Ocean Surface Parameters from SSM/I Data
Authors: Meng Lei , He Yijun , Chen Jinnian , Wu Yumei
Published: February 2007

A new algorithm based on the multiparameter neural network is proposed to retrieve wind speed (WS), sea surface temperature (SST), sea surface air temperature, and relative humidity (RH) simultaneously over the global oceans from Special Sensor Microwave Imager (SSM/I) observations. The retrieved geophysical parameters are used to estimate the surface latent heat flux and sensible heat flux using a bulk method over the global oceans. The neural network is trained and validated with the matchups of SSM/I overpasses and National Data Buoy Center buoys under both clear and cloudy weather conditions. In addition, the data acquired by the 85.5-GHz channels of SSM/I are used as the input variables of the neural network to improve its performance. The root-mean-square (rms) errors between the estimated WS, SST, sea surface air temperature, and RH from SSM/I observations and the buoy measurements are 1.48 m s−1, 1.54°C, 1.47°C, and 7.85, respectively. The rms errors between the estimated latent and sensible heat fluxes from SSM/I observations and the Xisha Island (in the South China Sea) measurements are 3.21 and 30.54 W m−2, whereas those between the SSM/I estimates and the buoy data are 4.9 and 37.85 W m−2, respectively. Both of these errors (those for WS, SST, and sea surface air temperature, in particular) are smaller than those by previous retrieval algorithms of SSM/I observations over the global oceans. Unlike previous methods, the present algorithm is capable of producing near-real-time estimates of surface latent and sensible heat fluxes for the global oceans from SSM/I data.
The Structure of Tornadoes near Attica, Kansas, on 12 May 2004: High-Resolution, Mobile, Doppler Radar Observations
Authors: Bluestein Howard B. , Weiss Christopher C. , French Michael M. , Holthaus Eric M. , Tanamachi Robin L. , Frasier Stephen , Pazmany Andrew L.
Published: February 2007

The University of Massachusetts W- and X-band, mobile, Doppler radars scanned several tornadoes at close range in south-central Kansas on 12 May 2004. The detailed vertical structure of the Doppler wind and radar reflectivity fields of one of the tornadoes is described with the aid of boresighted video. The inside wall of a weak-echo hole inside the tornado was terminated at the bottom as a bowl-shaped boundary within several tens of meters of the ground. Doppler signatures of horizontal vortices were noted along one edge in the lowest 500 m of the tornado. The vertical structure of Doppler velocity displayed significant variations on the 100-m scale. Near the center of the tornado, a quasi-horizontal, radial bulge of the weak-echo hole at ∼500–600 m AGL dropped to about 400 m above the ground and was evident as a weak-echo band to the south of the tornado. It is suggested that this feature represents echo-weak material transported radially outward by a vertical circulation. Significant vertical variations of Doppler velocity were found in the surface friction layer both inside and outside the tornado core. The shape of a weak-echo notch that was associated with a hook echo wrapped around the tornado is described. Highest Doppler velocities were located outside the condensation funnel. The structure of the other tornadoes is also described, but with much less detail. Some of the analyses are compared with numerical simulations of tornado-like vortices done elsewhere.
The Fidelity of NCEP CFS Seasonal Hindcasts over Nordeste
Authors: Misra Vasubandhu , Zhang Yuning
Published: February 2007

The fidelity of the interannual variability of precipitation over Nordeste is examined using the suite of the NCEP Climate Forecast System (CFS) seasonal hindcasts. These are coupled ocean–land–atmosphere multiseasonal integrations. It is shown that the Nordeste rainfall variability in the season of February–April has relatively low skill in the CFS seasonal hindcasts. Although Nordeste is a comparatively small region in the northeast of Brazil, the analysis indicates that the model has a large-scale error in the tropical Atlantic Ocean. The CFS exhibits a widespread El Niño–Southern Oscillation (ENSO) forcing over the tropical Atlantic Ocean. As a consequence of this remote ENSO forcing, the CFS builds an erroneous meridional SST gradient in the tropical Atlantic that is known from observations to be a critical forcing for the rainfall variability over Nordeste.
Dynamical and Synoptic Characteristics of Heavy Rainfall Episodes in Southern Brazil
Authors: Teixeira Mateusda Silva , Satyamurty Prakki
Published: February 2007

The dynamical and synoptic characteristics that distinguish heavy rainfall episodes from nonheavy rainfall episodes in southern Brazil are discussed. A heavy rainfall episode is defined here as one in which the 50 mm day−1 isohyet encloses an area of not less than 10 000 km2 in the domain of southern Brazil. One hundred and seventy such events are identified in the 11-yr period of 1991–2001. The mean flow patterns in the period of 1–3 days preceding the episodes show some striking synoptic-scale features that may be considered forerunners of these episodes: (i) a deepening midtropospheric trough in the eastern South Pacific approaches the continent 3 days before, (ii) a surface low pressure center forms in northern Argentina 1 day before, (iii) a northerly low-level jet develops over Paraguay 2 days before, and (iv) a strong moisture flux convergence over southern Brazil becomes prominent 1 day before the episode. A parameter called rainfall quantity, defined as the product of the area enclosed by the 50 mm day−1 isohyet and the average rainfall intensity, is correlated with fields of atmospheric variables such as 500-hPa geopotential and 850-hPa meridional winds. Significant lag correlations show that the anomalies of some atmospheric variables could be viewed as precursors of heavy rainfall in southern Brazil that can be explored for use in improving the forecasts.
Effect of Convective Entrainment/Detrainment on the Simulation of the Tropical Precipitation Diurnal Cycle*
Authors: Wang Yuqing , Zhou Li , Hamilton Kevin
Published: February 2007

A regional atmospheric model (RegCM) developed at the International Pacific Research Center (IPRC) is used to investigate the effect of assumed fractional convective entrainment/detrainment rates in the Tiedtke mass flux convective parameterization scheme on the simulated diurnal cycle of precipitation over the Maritime Continent region. Results are compared with observations based on 7 yr of the Tropical Rainfall Measuring Mission (TRMM) satellite measurements. In a control experiment with the default fractional convective entrainment/detrainment rates, the model produces results typical of most other current regional and global atmospheric models, namely a diurnal cycle with precipitation rates over land that peak too early in the day and with an unrealistically large diurnal range. Two sensitivity experiments were conducted in which the fractional entrainment/detrainment rates were increased in the deep and shallow convection parameterizations, respectively. Both of these modifications slightly delay the time of the rainfall-rate peak during the day and reduce the diurnal amplitude of precipitation, thus improving the simulation of precipitation diurnal cycle to some degree, but better results are obtained when the assumed entrainment/detrainment rates for shallow convection are increased to the value consistent with the published results from a large eddy simulation (LES) study. It is shown that increasing the entrainment/detrainment rates would prolong the development and reduce the strength of deep convection, thus delaying the mature phase and reducing the amplitude of the convective precipitation diurnal cycle over the land. In addition to the improvement in the simulation of the precipitation diurnal cycle, convective entrainment/detrainment rates also affect the simulation of temporal variability of daily mean precipitation and the partitioning of stratiform and convective rainfall in the model. The simulation of the observed offshore migration of the diurnal signal is realistic in some regions but is poor in some other regions. This discrepancy seems not to be related to the convective lateral entrainment/detrainment rate but could be due to the insufficient model resolution used in this study that is too coarse to resolve the complex land–sea contrast.
Sensitivities of a Flash Flood Event over Catalonia: A Numerical Analysis
Authors: Martín A. , Romero R. , De Luque A. , Alonso S. , Rigo T. , Llasat M. C.
Published: February 2007

On 9 and 10 June 2000, the northeastern part of the Iberian Peninsula was affected by heavy rains that produced severe floods over densely populated areas. The zones most affected were the provinces of Tarragona and Barcelona, located in the region of Catalonia. Five people were killed, 500 were evacuated, and the property losses were estimated to exceed 65 million euros. The episode was characterized by the entrance of an Atlantic low-level cold front and an upper-level trough that contributed to the generation of a mesoscale cyclone in the Mediterranean Sea east of mainland Spain. The circulation associated with this mesoscale cyclone advected warm and moist air toward Catalonia from the Mediterranean Sea. The convergence zone between the easterly flow and the Atlantic front, as well as the complex orography of the region, are shown to be involved in the triggering and organization of the convective systems. Radar shows the development of two long-lived mesoscale convective systems that merged and remained quasi-stationary nearby the city of Barcelona for nearly 2 h.

The fifth-generation Pennsylvania State University–National Center for Atmospheric Research (PSU–NCAR) Mesoscale Model (MM5) short-range numerical simulations of the episode succeed reasonably well in capturing the accumulated rainfall patterns and important mesoscale aspects of the event. The role of the orography and latent heat release in generating and sustaining the quasi-stationary precipitating systems is assessed through numerical sensitivity analysis. A piecewise potential vorticity inversion technique, assisted by sensitivity fields derived from an adjoint model, provides a test bed to investigate the predictability of the damaging rains given uncertainties in the initial fields. The adjoint results highlight the importance of the details associated with the upper-level precursor trough. Therefore, the effects of small perturbations to the trough intensity and location are also investigated. Interestingly, despite the orography’s active role in the generation of the Mediterranean mesoscale cyclone and, hence, on the location of the precipitation maxima, the predictability of the spatial and temporal distribution and amounts of precipitation is shorter than might be expected. This reduced predictability of the rainfall field is attributed to the high sensitivity of the location and depth of the mesoscale cyclone identified in the Mediterranean Sea east of Catalonia to perturbations; that is, to the location and intensity of the precursor upper-level trough, compatible with realistic analysis errors.
Non-Gaussianity and Asymmetry of the Winter Monthly Precipitation Estimation from the NAO
Authors: Pires Carlos A. , Perdigão Rui A. P.
Published: February 2007

The present work assesses non-Gaussianity and asymmetry within the statistical response of the monthly winter (December–February) precipitation to the North Atlantic Oscillation (NAO) over the North Atlantic–European region (NAE). To evaluate asymmetry, data are split through the median of the NAO index and side correlations are computed for each regime [negative and positive phases of the NAO (NAO− and NAO+, respectively)]. The following statistically significant differences between these correlations are found: (a) near the central North Atlantic, around 40°N, 20°W, and southeast of Iceland, with much stronger correlations in the wet-favorable regime: NAO− in the first location and NAO+ in the second location; (b) around 42°N, 48°W in the west North Atlantic; and (c) south of Greenland and in the west Mediterranean near 36°N, where, in both cases, the correlation is only relevant for the dry-favorable NAO+ regime. Based on the above decomposition, a map of a statistical test of asymmetry, applicable for every bivariate distribution, is shown.

To evaluate redundancy and non-Gaussianity, the mutual information (MI) is computed from information theory. Its positive contributions resulting from the linear correlation, a purely Gaussian term, and non-Gaussianity, which vanishes in pure Gaussian cases, are studied. The MI is estimated through two methods: 1) the truncated Edgeworth expansion of the bivariate probability density function in terms of Hermite polynomials and cumulants, and 2) the maximum entropy method. This method is quite general, while the first one is only applicable for small deviations from Gaussianity. The map of non-Gaussian MI over the NAE domain reveals some coherent regions, where the nonlinear component of the response of monthly winter precipitation to the NAO is more important. The MI is evaluated both for the original pair of variables and for that pair after being subjected to Gaussian anamorphosis in order to prevent the influence of marginal outliers and keep the applicability of the Edgeworth method.
Gender Differences in the Effects of Strain on the Delinquency of South Korean Youth
Authors: Morash Merry , Moon Byongook
Published: February 2007

General strain theory (GST) was tested as an explanation of violent and status offense delinquency of South Korean girls and boys. One research objective was to determine whether Korean girls and boys differed in their experience of each type of strain and in the levels of conditioning effects that might moderate the connections of strain to delinquency. Another objective was to identify gender differences in the effects of different types of strain, conditioning effects, and interaction terms (Strains × Conditioning factors) on delinquency. Finally, the study compared girls and boys on the amount of variance in delinquency that main and interaction effects explained. For both gender groups, the interaction of abuse by teachers and having delinquent peers stood out as the key predictor of violent and status offending.
Sex Differences in the Multidimensional Self-Concepts of African American Adolescents: The Mediating Role of Gender Identity
Authors: Thomson Nicole Renick , Zand Debra H.
Published: February 2007

The present study investigates whether the gender identities of African American adolescents mediate sex differences found in their multidimensional self-concepts. The sample included 174 African American adolescents who completed the 21-item Children's Personal Attributes Questionnaire and the Self-Perception Profile for Adolescents. Results indicated that two dimensions of gender identity, Independence and Leadership, mediated the relationship between sex and self-evaluations in the areas of Friendship/Acceptance and Romantic Appeal. The findings of this study fill significant gaps in the current literature by providing data on African American adolescents' self-evaluations in multiple self-concept domains and by offering an empirical explanation for how biological sex influences these self-evaluations. Implications of these findings and directions for future research are discussed.
The Engagement in Schooling of Economically Disadvantaged Parents and Children
Authors: Cooper Carey E. , Crosnoe Robert
Published: February 2007

This study considers academic risk and resilience in the context of economic disadvantage, examining the associations among such disadvantage, parental involvement in education, and children's academic orientation in a sample of 489 inner-city families. Neither parents' nor children's engagement in the educational system was significantly associated with a multidimensional scale of economic disadvantage after accounting for demographic characteristics and children's academic achievement. The association between parental involvement and academic orientation, however, differed by level of economic disadvantage. In economically disadvantaged families, parental involvement was associated with greater levels of child academic orientation. In other families, parental involvement and academic orientation were inversely associated with each other.
Herpes Zoster in the T4 Dermatome: A Possible Cause of Breastfeeding Strike
Authors: Mathers Lawrence J. , Mathers Rachel A. , Brotherton Deana R.
Published: February 2007

The authors report a case of breastfeeding strike temporally related to the onset of a herpes zoster prodrome involving the left breast.
Predictors of Preterm Infant Feeding Methods and Perceived Insufficient Milk Supply at Week 12 Postpartum
Authors: Hill Pamela D. , Aldag Jean C. , Zinaman Michael , Chatterton Robert T.
Published: February 2007

As part of a large, nonexperimental, prospective, longitudinal study, 94 pump-dependent mothers of a nonnursing preterm infant were queried via telephone at weeks 8 to 12 post-partum about their infant feeding method. At week 12, 44.6% provided own mother’s milk, 26.6% provided own mother’s milk + artificial milk, and 28.7% provided artificial milk only. Logistic regression analyses identified the following predictors for risk of artificial milk at week 12 postpartum: multiple birth, week 6 inadequate milk supply, maternal age younger than 29 years, and intended length of lactation less than 34 weeks. Predictors for risk of maternal perceived insufficient milk supply for weeks 8 to 12 postpartum included week 6 inadequate milk supply, unemployment, and infant hospital discharge after postpartum day 42. Further research is needed to assist pump-dependent mothers of preterm infants with sustaining their milk supply.
Understanding Breastfeeding Behavior: Rates and Shifts in Patterns in Québec
Authors: Haiek Laura N. , Gauthier Dany L. , Brosseau Dominique , Rocheleau Lydia
Published: February 2007

The study objective was to measure breastfeeding rates and patterns in the Montérégie region of Québec. A survey of 632 mothers of 6-month-old infants was performed, of which 80% initiated breastfeeding, and 68% exclusively breastfed at birth. Breastfeeding rates progressively decreased with time: 63%, 56%, 51%, 44%, 39%, and 32% of mothers breastfed at 1, 2, 3, 4, 5, and 6 months, respectively. Among mothers breastfeeding at a given period, 62%, 57%, 48%, 35%, and 10% of women exclusively breastfed since birth for 1, 2, 3, 4, and 5 months, respectively. Exclusive breastfeeding for 6 months among the 200 women still breastfeeding was practically nonexistent. Introduction of nonhuman milk or solids was primarily responsible for the shift in patterns from exclusive to complementary feeding without passing through predominant breastfeeding. These findings confirm the need to prioritize effective hospital-based and community-based interventions to increase breastfeeding duration and exclusivity in the region.
C-KIT, by interacting with the membrane-bound ligand, recruits endothelial progenitor cells to inflamed endothelium
Authors: Dentelli Patrizia , Rosso Arturo , Balsamo Antonina , Colmenares Benedetto Sofia , Zeoli Annarita , Pegoraro Marco , Camussi Giovanni , Pegoraro Luigi , Brizzi Maria Felice
Published: February 2007

We investigated the role of c-Kit and the membrane-bound ligand (mbKitL) in endothelial progenitor cell (EPC) recruitment by microvascular endothelial cells (ECs). We demonstrated that inflammatory activation induced the expression of the mbKitL on ECs both in vitro and in vivo, and that recruitment of EPCs depended on c-Kit/mbKitL interaction. Depletion of endogenous c-Kit or inhibition of c-Kit enzymatic activity by imatinib mesylate prevented adhesion of EPCs to activated ECs both in vitro and in vivo, indicating that a functional c-Kit on EPCs is essential. We also demonstrate that Akt was the downstream molecule regulating cell adhesion. A potential role of the c-Kit/mbKitL interaction in pathological settings is sustained by the expression of the mbKitL on ECs lining intraplaque neovessels. Thus, our results provide new insights into the mechanisms underlying EPC recruitment and the bases for novel strategies to hinder pathological angiogenesis.
Blood and lymphatic endothelial cell-specific differentiation programs are stringently controlled by the tissue environment
Authors: Amatschek Stefan , Kriehuber Ernst , Bauer Wolfgang , Reininger Barbel , Meraner Paul , Wolpl Alois , Schweifer Norbert , Haslinger Christian , Stingl Georg , Maurer Dieter
Published: February 2007

The discovery of marker proteins of human blood (BECs) and lymphatic endothelial cells (LECs) has allowed researchers to isolate these cells. So far, efforts to unravel their transcriptional and functional programs made use of cultured cells only. Hence, it is unknown to which extent previously identified LEC- and BEC-specific programs are representative of the in vivo situation. Here, we define the human BEC- and LEC-specific in vivo transcriptomes by comparative genomewide expression profiling of freshly isolated cutaneous EC subsets and of non-EC skin cells (fibroblasts, mast cells, dendritic cells, epithelial cells). Interestingly, the expression of most of the newly identified EC subset-discriminating genes depends strictly on the in vivo tissue environment as revealed by comparative analyses of freshly isolated and cultured EC subsets. The identified environment-dependent, EC subset-restricted gene expression regulates lineage fidelity, fluid exchange, and MHC class II–dependent antigen presentation. As an example for a BEC-restricted in vivo function, we show that non-activated BECs in situ, but not in vitro, assemble and display MHC class II protein complexes loaded with self-peptides. Thus, our data demonstrate the key importance of using precisely defined native ECs for the global identification of in vivo relevant cell functions.
Abnormal activation and cytokine spectra in lymph nodes of people chronically infected with HIV-1
Authors: Biancotto Angélique , Grivel Jean-Charles , Iglehart Sarah J. , Vanpouille Christophe , Lisco Andrea , Sieg Scott F. , Debernardo Robert , Garate Kristen , Rodriguez Benigno , Margolis Leonid B. , Lederman Michael M.
Published: February 2007

There is growing recognition that HIV-1 infection leads to an activation of the immune system that includes perturbations of cytokine expression, redistribution of lymphocyte subpopulations, cell dysfunction, and cell death. Here, we explored the relationships between HIV-1 infection and immune activation in chronically HIV-1–infected human lymph nodes. In addition to CD4 T-cell depletion, we found increased effector T-cell frequencies associated with profound up-regulation of an activation marker CD38 in naive, central memory, and effector CD4+ and CD8+ T cells. Likewise, Fas death receptor (CD95) was more frequently detectable on T cells from HIV-1 nodes. Dendritic cell (DC) depletion was dramatic, with plasmacytoid DCs (PDCs) 40-fold and myeloid DCs (MDCs) 20-fold less frequent in HIV+ nodes than in control nodes. Cytokine dysregulation was evident, with IL-2 and IL-15 as much as 2 or 3 logs greater in infected nodes than in control nodes. Thus, activated effector cells are inappropriately attracted and/or retained in lymphoid tissue in chronic HIV-1 infection. High-level cytokine expression in turn activates and retains more cells at these sites, leading to lymphadenopathy and massive bystander activation that characterizes HIV-1 infection. Strategies targeting these activation pathways may lead to new therapies.
Upregulation of pirin expression by chronic cigarette smoking is associated with bronchial epithelial cell apoptosis
Authors: Gelbman Brian D , Heguy Adriana , O'Connor Timothy P , Zabner Joseph , Crystal Ronald G
Published: February 2007

Background

Cigarette smoke disrupts the protective barrier established by the airway epithelium through direct damage to the epithelial cells, leading to cell death. Since the morphology of the airway epithelium of smokers does not typically demonstrate necrosis, the most likely mechanism for epithelial cell death in response to cigarette smoke is apoptosis. We hypothesized that cigarette smoke directly up-regulates expression of apoptotic genes, which could play a role in airway epithelial apoptosis.

Methods

Microarray analysis of airway epithelium obtained by bronchoscopy on matched cohorts of 13 phenotypically normal smokers and 9 non-smokers was used to identify specific genes modulated by smoking that were associated with apoptosis. Among the up-regulated apoptotic genes was pirin (3.1-fold, p < 0.002), an iron-binding nuclear protein and transcription cofactor. In vitro studies using human bronchial cells exposed to cigarette smoke extract (CSE) and an adenovirus vector encoding the pirin cDNA (AdPirin) were performed to test the direct effect of cigarette smoke on pirin expression and the effect of pirin expression on apoptosis.

Results

Quantitative TaqMan RT-PCR confirmed a 2-fold increase in pirin expression in the airway epithelium of smokers compared to non-smokers (p < 0.02). CSE applied to primary human bronchial epithelial cell cultures demonstrated that pirin mRNA levels increase in a time-and concentration-dependent manner (p < 0.03, all conditions compared to controls).

Overexpression of pirin, using the vector AdPirin, in human bronchial epithelial cells was associated with an increase in the number of apoptotic cells assessed by both TUNEL assay (5-fold, p < 0.01) and ELISA for cytoplasmic nucleosomes (19.3-fold, p < 0.01) compared to control adenovirus vector.

Conclusion

These observations suggest that up-regulation of pirin may represent one mechanism by which cigarette smoke induces apoptosis in the airway epithelium, an observation that has implications for the pathogenesis of cigarette smoke-induced diseases.
Phylogenetic analyses of complete mitochondrial genome sequences suggest a basal divergence of the enigmatic rodent Anomalurus
Authors: Horner David S , Lefkimmiatis Konstantinos , Reyes Aurelio , Gissi Carmela , Saccone Cecilia , Pesole Graziano
Published: February 2007

Background

Phylogenetic relationships between Lagomorpha, Rodentia and Primates and their allies (Euarchontoglires) have long been debated. While it is now generally agreed that Rodentia constitutes a monophyletic sister-group of Lagomorpha and that this clade (Glires) is sister to Primates and Dermoptera, higher-level relationships within Rodentia remain contentious.

Results

We have sequenced and performed extensive evolutionary analyses on the mitochondrial genome of the scaly-tailed flying squirrel Anomalurus sp., an enigmatic rodent whose phylogenetic affinities have been obscure and extensively debated. Our phylogenetic analyses of the coding regions of available complete mitochondrial genome sequences from Euarchontoglires suggest that Anomalurus is a sister taxon to the Hystricognathi, and that this clade represents the most basal divergence among sampled Rodentia. Bayesian dating methods incorporating a relaxed molecular clock provide divergence-time estimates which are consistently in agreement with the fossil record and which indicate a rapid radiation within Glires around 60 million years ago.

Conclusion

Taken together, the data presented provide a working hypothesis as to the phylogenetic placement of Anomalurus, underline the utility of mitochondrial sequences in the resolution of even relatively deep divergences and go some way to explaining the difficulty of conclusively resolving higher-level relationships within Glires with available data and methodologies.
Modulation of eosinophil activation in vitro by a nicotinic receptor agonist
Authors: Blanchet Marie-Renée , Langlois Anick , Israël-Assayag Evelyne , Beaulieu Marie-Josée , Ferland Claudine , Laviolette Michel , Cormier Yvon
Published: February 2007

Nicotinic receptor agonists decreased the infiltration of eosinophils into the lung and airways in a mouse model of asthma. To better understand the mechanisms implicated in this anti-inflammatory phenomenon, the expression of nicotinic acetylcholine receptors (nAChRs) and the effect of dimethylphenylpiperazinium (DMPP), a nonselective nAChR agonist, on human blood eosinophils were studied. The expression of α-3, -4, and -7 nAChR subunits on human blood eosinophils was measured by cell ELISA and immunocytochemistry. mRNA expression for all three subunits was evaluated by quantitative RT-PCR. The effect of DMPP on leukotriene C4 (LTC4) and matrix metalloproteinase-9 (MMP-9) production, eosinophil migration, and intracellular calcium mobilization was measured. The results show that the α-3, -4, and -7 nAChR subunits and mRNAs are expressed by blood eosinophils. In vitro treatment of these cells with various concentrations of DMPP reduced platelet-activating factor (PAF)-induced LTC4 production significantly. DMPP (160 μM) decreased eotaxin, and 5-oxo-6,8,11,14-eicosatetranoic acid induced eosinophil migration through Matrigel by 40.9% and 55.5%, respectively. This effect was reversed by the nAChR antagonist mecamylamine. In addition, DMPP reduced MMP-9 release and the inositol 1,4,5-triphosphate-dependent intracellular calcium increase provoked by PAF. Taken together, these results indicate that functional nAChRs are expressed on eosinophils and that nAChR agonists down-regulate eosinophil function in vitro. These anti-inflammatory effects could be of interest in the treatment of allergic asthma.
Hydrogen sulfide induces the synthesis of proinflammatory cytokines in human monocyte cell line U937 via the ERK-NF-κB pathway
Authors: Zhi Liang , Ang Abel Damien , Zhang Huili , Moore Philip K , Bhatia Madhav
Published: February 2007

Hydrogen sulfide (H2S) is now considered an endogenous, gaseous mediator, which has been demonstrated to be involved in many inflammatory states. However, the mechanism of its proinflammatory function remains unknown. In the present study, we used IFN-γ-primed human monocyticcell line U937 to investigate the effects of H2S in vitro on monocytes. We found that treatment with the H2S donor, sodium hydrosulfide, led to significant increases in the mRNA expression and protein production of TNF-α, IL-1β, and IL-6 in U937 cells. H2S-triggered monocyte activation was confirmed further by the up-regulation of CD11b expression on the cell surface. We also observed that H2S could induce a rapid degradation of IκBα and subsequent activation of NF-κB p65, and this effect was attenuated by Bay 11-7082, a specific inhibitor of NF-κB. Furthermore, pretreatment of cells with Bay 11-7082 substantially inhibited the secretion of TNF-α, IL-1β, and IL-6 induced by H2S. We also found that H2S stimulated the phosphorylation and activation of ERK1/2, but not of p38 MAPK and JNK, and pretreatment with PD98059, a selective MEK1 antagonist, could inhibit H2S-induced NF-κB activation markedly. Together, our findings suggest for the first time that H2S stimulates the activation of human monocytes with the generation of proinflammatory cytokines, and this response is, at least partially, through the ERK-NF-κB signaling pathway.
Dexrazoxane-Associated Risk for Acute Myeloid Leukemia/Myelodysplastic Syndrome and Other Secondary Malignancies in Pediatric Hodgkin's Disease
Authors: Tebbi Cameron K. , London Wendy B. , Friedman Debra , Villaluna Doojduen , De Alarcon Pedro A. , Constine Louis S. , Mendenhall Nancy Price , Sposto Richard , Chauvenet Allen , Schwartz Cindy L.
Published: February 2007

Purpose

Pediatric Oncology Group (POG) studies 9426 and 9425 evaluated dexrazoxane (DRZ) as a cardiopulmonary protectant during treatment for Hodgkin's disease (HD). We evaluated incidence and risk factors of acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS) and second malignant neoplasms (SMNs).

Patients and Methods

Treatment for low- and high-risk HD with doxorubicin, bleomycin, vincristine, and etoposide (ABVE) or dose-intensified ABVE with prednisone and cyclophosphamide (ABVE-PC), respectively, was followed by low-dose radiation. The number of chemotherapy cycles was determined by rapidity of the initial response. Patients were assigned randomly to receive DRZ (n = 239) or no DRZ (n = 239) concomitantly with chemotherapy to evaluate its potential to decrease adverse cardiopulmonary outcomes.

Results

Ten patients developed SMN. Six of eight patients developed AML/MDS, and both solid tumors (osteosarcoma and papillary thyroid carcinoma) occurred in recipients of DRZ. Eight patients with SMN were first events. With median 58 months' follow-up, 4-year cumulative incidence rate (CIR) for AML/MDS was 2.55% ± 1.0% with DRZ versus 0.85% ± 0.6% in the non-DRZ group (P = .160). For any SMN, the CIR for DRZ was 3.43% ± 1.2% versus CIR for non-DRZ of 0.85% ± 0.6% (P = .060). Among patients receiving DRZ, the standardized incidence rate (SIR) for AML/MDS was 613.6 compared with 202.4 for those not receiving DRZ (P = .0990). The SIR for all SMN was 41.86 with DRZ versus 10.08 without DRZ (P = .0231).

Conclusion

DRZ is a topoisomerase II inhibitor with a mechanism distinct from etoposide and doxorubicin. Adding DRZ to ABVE and ABVE-PC may have increased the incidence of SMN and AML/MDS.
An Integrated Genomic-Based Approach to Individualized Treatment of Patients With Advanced-Stage Ovarian Cancer
Authors: Dressman Holly K. , Berchuck Andrew , Chan Gina , Zhai Jun , Bild Andrea , Sayer Robyn , Cragun Janiel , Clarke Jennifer , Whitaker Regina S. , Li LiHua , Gray Jonathan , Marks Jeffrey , Ginsburg Geoffrey S. , Potti Anil , West Mike , Nevins Joseph R. , Lancaster Johnathan M.
Published: February 2007

Purpose

The purpose of this study was to develop an integrated genomic-based approach to personalized treatment of patients with advanced-stage ovarian cancer. We have used gene expression profiles to identify patients likely to be resistant to primary platinum-based chemotherapy and also to identify alternate targeted therapeutic options for patients with de novo platinum-resistant disease.

Patients and Methods

A gene expression model that predicts response to platinum-based therapy was developed using a training set of 83 advanced-stage serous ovarian cancers and tested on a 36-sample external validation set. In parallel, expression signatures that define the status of oncogenic signaling pathways were evaluated in 119 primary ovarian cancers and 12 ovarian cancer cell lines. In an effort to increase chemotherapy sensitivity, pathways shown to be activated in platinum-resistant cancers were subject to targeted therapy in ovarian cancer cell lines.

Results

Gene expression profiles identified patients with ovarian cancer likely to be resistant to primary platinum-based chemotherapy with greater than 80% accuracy. In patients with platinum-resistant disease, we identified expression signatures consistent with activation of Src and Rb/E2F pathways, components of which were successfully targeted to increase response in ovarian cancer cell lines.

Conclusion

We have defined a strategy for treatment of patients with advanced-stage ovarian cancer that uses therapeutic stratification based on predictions of response to chemotherapy, coupled with prediction of oncogenic pathway deregulation, as a method to direct the use of targeted agents.
Lung Cancer in Never Smokers: A Review
Authors: Subramanian Janakiraman , Govindan Ramaswamy
Published: February 2007

Lung cancer is the leading cause of cancer-related death in the United States. Although tobacco smoking accounts for the majority of lung cancer, approximately 10% of patients with lung cancer in the United States are lifelong never smokers. Lung cancer in the never smokers (LCINS) affects women disproportionately more often than men. Only limited data are available on the etiopathogenesis, molecular abnormalities, and prognosis of LCINS. Several etiologic factors have been proposed for the development of LCINS, including exposure to radon, cooking fumes, asbestos, heavy metals, and environmental tobacco smoke, human papillomavirus infection, and inherited genetic susceptibility. However, the relative significance of these individual factors among different ethnic populations in the development of LCINS has not been well-characterized. Adenocarcinoma is the predominant histologic subtype reported with LCINS. Striking differences in response rates and outcomes are seen when patients with advanced non–small-cell lung cancer (NSCLC) who are lifelong never smokers are treated with epidermal growth factor receptor tyrosine kinase (EGFR-TK) inhibitors such as gefitinib or erlotinib compared with the outcomes with these agents in patients with tobacco-associated lung cancer. Interestingly, the activating mutations in the EGFR-TK inhibitors have been reported significantly more frequently in LCINS than in patients with tobacco-related NSCLC. This review will summarize available data on the epidemiology, risk factors, molecular genetics, management options, and outcomes of LCINS.
Molecular Predictors of Response to Epidermal Growth Factor Receptor Antagonists in Non–Small-Cell Lung Cancer
Authors: Sequist Lecia V. , Bell Daphne W. , Lynch Thomas J. , Haber Daniel A.
Published: February 2007

In the last 5 years the epidermal growth factor receptor (EGFR) has emerged as one of the most important targets for drug development in oncology. Monoclonal antibodies targeting the external domain of EGFR have been shown to have clinical benefit in colorectal and head and neck cancer when combined with chemotherapy and/or radiation. Small molecules that inhibit the tyrosine kinase (TK) domain of EGFR have become critical new weapons in the treatment of non–small-cell lung cancer (NSCLC). The discovery that mutations in the TK domain are associated with dramatic and sustained responses to EGFR TK inhibitors (TKIs) has allowed the design of trials to test these agents as potential first-line therapies and has provided a fascinating window into the future of genotype-directed targeted therapy. Recent advances in understanding the biologic basis of acquired resistance to these agents have great potential to improve the clinical effectiveness of this class of drugs. This review summarizes the biology of EGFR in NSCLC, the clinical and molecular predictors of benefit from treatment with EGFR TKIs, the use of patient-specific molecular profiling, and future directions of clinical and basic scientific research.
Vascular Targeted Therapy With Anti–Prostate-Specific Membrane Antigen Monoclonal Antibody J591 in Advanced Solid Tumors
Authors: Milowsky Matthew I. , Nanus David M. , Kostakoglu Lale , Sheehan Christine E. , Vallabhajosula Shankar , Goldsmith Stanley J. , Ross Jeffrey S. , Bander Neil H.
Published: February 2007

Purpose

Based on prostate-specific membrane antigen (PSMA) expression on the vasculature of solid tumors, we performed a phase I trial of antibody J591, targeting the extracellular domain of PSMA, in patients with advanced solid tumor malignancies. This was a proof-of-principle evaluation of PSMA as a potential neovascular target. The primary end points were targeting,toxicity, maximum-tolerated dose, pharmacokinetics (PK), and human antihuman antibody (HAHA) response.

Patients and Methods

Patients had advanced solid tumors previously shown to express PSMA on the neovasculature. They received111Indium (111ln)-J591 for scintigraphy and PK, followed 2 weeks later by J591 with a reduced amount of111In for additional PK measurements. J591 dose levels were 5, 10, 20, 40, and 80 mg. The protocol was amended for six weekly administrations of unchelated J591. Patients with a response or stable disease were eligible for re-treatment. Immunohistochemistry assessed PSMA expression in tumor tissues.

Results

Twenty-seven patients received monoclonal antibody (mAb) J591. Treatment was well tolerated. Twenty (74%) of 27 patients had at least one area of known metastatic disease targeted by111In-J591, with positive imaging seen in patients with kidney, bladder, lung, breast, colorectal, and pancreatic cancers, and melanoma. Seven of 10 patient specimens available for immunohistochemical assessment of PSMA expression in tumor-associated vasculature demonstrated PSMA staining. No HAHA response was seen. Three patients of 27 with stable disease received re-treatment.

Conclusion

Acceptable toxicity and excellent targeting of known sites of metastases were demonstrated in patients with multiple solid tumor types, highlighting a potential role for the anti-PSMA antibody J591 as a vascular-targeting agent.
Role of Microsomal Retinol/Sterol Dehydrogenase-Like Short-Chain Dehydrogenases/Reductases in the Oxidation and Epimerization of 3α-Hydroxysteroids in Human Tissues
Authors: Belyaeva Olga V. , Chetyrkin Sergei V. , Clark Amy L. , Kostereva Natalia V. , SantaCruz Karen S. , Chronwall Bibie M. , Kedishvili Natalia Y.
Published: February 2007

Allopregnanolone (ALLO) and androsterone (ADT) are naturally occurring 3α-hydroxysteroids that act as positive allosteric regulators of γ-aminobutyric acid type A receptors. In addition, ADT activates nuclear farnesoid X receptor and ALLO activates pregnane X receptor. At least with respect to γ-aminobutyric acid type A receptors, the biological activity of ALLO and ADT depends on the 3α-hydroxyl group and is lost upon its conversion to either 3-ketosteroid or 3β-hydroxyl epimer. Such strict structure-activity relationships suggest that the oxidation or epimerization of 3α-hydroxysteroids may serve as physiologically relevant mechanisms for the control of the local concentrations of bioactive 3α-hydroxysteroids. The exact enzymes responsible for the oxidation and epimerization of 3α-hydroxysteroids in vivo have not yet been identified, but our previous studies showed that microsomal nicotinamide adenine dinucleotide-dependent short-chain dehydrogenases/reductases (SDRs) with dual retinol/sterol dehydrogenase substrate specificity (RoDH-like group of SDRs) can oxidize and epimerize 3α-hydroxysteroids in vitro. Here, we present the first evidence that microsomal nicotinamide adenine dinucleotide-dependent 3α-hydroxysteroid dehydrogenase/epimerase activities are widely distributed in human tissues with the highest activity levels found in liver and testis and lower levels in lung, spleen, brain, kidney, and ovary. We demonstrate that RoDH-like SDRs contribute to the oxidation and epimerization of ALLO and ADT in living cells, and show that RoDH enzymes are expressed in tissues that have microsomal 3α-hydroxysteroid dehydrogenase/epimerase activities. Together, these results provide further support for the role of RoDH-like SDRs in human metabolism of 3α-hydroxysteroids and offer a new insight into the enzymology of ALLO and ADT inactivation.
A Role for β-Cell-Expressed G Protein-Coupled Receptor 119 in Glycemic Control by Enhancing Glucose-Dependent Insulin Release
Authors: Chu Zhi-Liang , Jones Robert M. , He Hongmei , Carroll Chris , Gutierrez Veronica , Lucman Annette , Moloney Molly , Gao Hui , Mondala Helen , Bagnol Didier , Unett David , Liang Yin , Demarest Keith , Semple Graeme , Behan Dominic P. , Leonard James
Published: February 2007

Pancreatic β-cell dysfunction is a hallmark event in the pathogenesis of type 2 diabetes. Injectable peptide agonists of the glucagon-like peptide 1 (GLP-1) receptor have shown significant promise as antidiabetic agents by virtue of their ability to amplify glucose-dependent insulin release and preserve pancreatic β-cell mass. These effects are mediated via stimulation of cAMP through β-cell GLP-1 receptors. We report that the Gαs-coupled receptor GPR119 is largely restricted to insulin-producing β-cells of pancreatic islets. Additionally, we show here that GPR119 functions as a glucose-dependent insulinotropic receptor. Unlike receptors for GLP-1 and other peptides that mediate enhanced glucose-dependent insulin release, GPR119 was suitable for the development of potent, orally active, small-molecule agonists. The GPR119-specific agonist AR231453 significantly increased cAMP accumulation and insulin release in both HIT-T15 cells and rodent islets. In both cases, loss of GPR119 rendered AR231453 inactive. AR231453 also enhanced glucose-dependent insulin release in vivo and improved oral glucose tolerance in wild-type mice but not in GPR119-deficient mice. Diabetic KK/Ay mice were also highly responsive to AR231453. Orally active GPR119 agonists may offer significant promise as novel antihyperglycemic agents acting in a glucose-dependent fashion.
Real-time PCR Assay for Ultrasensitive Quantification of DNA-Binding Proteins
Authors: Hou Peng , Chen Zaozao , Ji Meiju , He Nongyue , Lu Zuhong
Published: February 2007

Background: The specific binding of proteins to DNA is a key step for many cellular activities, such as transcription regulation, DNA replication, recombination, repair, and restriction. The detection of DNA-binding proteins, as well as the identification of specific binding sites, is therefore important to understand gene expression mechanisms and cellular function. We describe an ultrasensitive method for quantification of DNA-binding proteins.

Methods: We combined the common exonuclease III (ExoIII) footprinting assay and real-time PCR for quantification of DNA-binding proteins, for an assay that does not require antibodies against the target proteins. Double-strand DNA probes were designed to monitor the activities of DNA-binding protein. The protein-binding site is at the 5′ end of the forward primer. When a target protein is present, it will specifically bind to the protein-binding site and produce a physical hindrance to ExoIII, which protects the reverse DNA strand from digestion by ExoIII. The remaining single-strand DNA template can be quantitatively detected by real-time PCR. Conversely, in the absence of the target protein, the naked primer regions will be degraded by ExoIII, which then cannot be amplified by real-time PCR.

Results: We detected the binding of 10 different transcription factors in crude cell extracts. The assay quantitatively detected binding at femtomolar concentrations of protein.

Conclusions: This technique is customizable and easy to establish. It has potential applications in research, medical diagnosis, and drug discovery.
A CMOS Range Camera based on Single Photon Avalanche Diodes (CMOS-Range-Kamera mit Single-Photon-Avalanche-Photodioden)
Authors: Pancheri Lucio , Stoppa David , Gonzo Lorenzo , Dalla Betta Gian-Franco
Published: February 2007

This paper reports on a novel range camera employing Single Photon Avalanche Diodes for Time-of-Flight imaging applications. The architecture of an active pixel containing a single photon detector and the relative read-out channel is presented together with experimental results of a 64-pixel linear array. The sensor array, fabricated with a standard high-voltage 0.8-μm CMOS technology, exhibits a range accuracy of better than ± 3cm in the range interval 2m to 5m, without any external averaging operation.
Abtastung schmalbandiger Signale und ihre Anwendung zur Hüllkurvenanalyse bei rechnergestützten schwingungsdiagnostischen Systemen (Sampling of Narrow Band Signals and its Application for Envelope Analysis in Computer-aided Diagnosis Systems)
Authors: Liu Zhongdong , Nötzel Ralf , Bonfig Karl-Walter
Published: February 2007

Im Beitrag wird ein modifiziertes Verfahren zur Fehlererkennung an Wälzlagern unter Nutzung der Hüllkurvenanalyse vorgestellt. Es wird dabei der Nachweis erbracht, dass beim Vorliegen von schmalbandigen Signalen die Abtastfrequenz zur Signalerfassung dabei niedriger als die vom Abtasttheorem verlangte Abtastfrequenz liegen kann. Darauf aufbauend wird dieses Verfahren anhand von numerischen Beispielen näher erläutert. Ergebnisse praktisch durchgeführter Messungen an einem Versuchsaufbau schließen den Beitrag ab.
Struggling to Connect: White and Black Feminism in the Movement Years
Authors: Breines Winifred
Published: February 2007

Why did an interracial feminist movement fail to develop in the United States? Were white feminists racist?
Science, Politics, and Forensics
Authors: Timmermans Stefan
Published: February 2007

Suspicious deaths have been with us since the first hominids, or before. Better scientific explanations have often come at the cost of full social understanding.