bluuebunny/crossref_metadata_2025 huggingface dataset:
Low-grade abdominopelvic sarcoma with myofibroblastic features (low-grade myofibroblastic sarcoma): clinicopathological, immunohistochemical, molecular genetic and ultrastructural study of two cases with literature review
Authors: Agaimy A , Wünsch P H , Schroeder J , Gaumann A , Dietmaier W , Hartmann A , Hofstaedter F , Mentzel T
Published: May 2007

Aims:

Low-grade myofibroblastic sarcoma (LGMS) represents a rare soft tissue neoplasm with a predilection for the head and neck. Intra-abdominal LGMS are rare with only four unequivocal examples reported so far. Two further cases in females in their 60s and 70s are analysed here.

Methods:

Immunohistochemical stains were applied on fresh-cut sections using the avidin–biotin complex method and the following antibodies: vimentin, α-SMA, desmin, h-caldesmon, S-100, CD117, CD34, fibronectin, HMB45, Pan-keratin, Ki-67, β-catenin, MDM2, PDGFRα, PDGFRβ and ALK-1. Genomic DNA was isolated from microdissected formalin-fixed paraffin-embedded tumour tissue and examined forKITandPDGFRAmutations by PCR and direct sequencing ofKITandPDGFRA.Ultrastructural studies were also performed.

Results:

The tumours arose in the mesentery and the pelvic peritoneum. Both revealed features intermediate between conventional fibrosarcoma and leiomyosarcoma with fascicles of spindled, stellated or plump cells possessing fusiform indented vesicular nuclei and pale eosinophilic cytoplasm. Mitotic activity ranged from 1 to 15 per 10 HPFs. The tumour cells strongly expressed vimentin, variably α-smooth muscle actin and fibronectin, but were negative for CD117, S-100, desmin, h-caldesmon, β-catenin, ALK-1, MDM2, PDGFRα and PDGFRβ. One tumour showed a weak expression of CD34. Molecular analysis revealed a wild-typeKIT, exons 9, 11 and 13, andPDGFRA, exons 12 and 18. The patients developed multiple peritoneal recurrences at 5, 13 and 25 months, and 10, 19, 25 and 32 months, and were alive at 25 and 32 months, respectively. Distant metastases were not detected.

Conclusion:

Abdominopelvic LGMS follows a more aggressive clinical course characterised by a higher propensity for local recurrence, contrasting their more superficially located counterparts. LGMS may mimic a variety of benign and low-grade malignant neoplasms and might be under-recognised.
Influences of fire on forest soil fungal communitiesThis article is one of a selection of papers published in the Special Forum on Towards Sustainable Forestry — The Living Soil: Soil Biodiversity and Ecosystem Function.
Authors: Cairney John W.G. , Bastias Brigitte A.
Published: May 2007

Wildfires and prescribed burns constitute widespread and potentially destructive disturbances in forest ecosystems. Fire-related effects on aboveground ecosystem components are well established, and it is known that fire can have both a direct and an indirect influence on the edaphic environment, but the effects of fire on soil-dwelling fungi are poorly understood. We review the disparate literature relating to fire effects on soil fungi, with emphasis on forest environments. A variety of effects have been reported, including altered fungal community structure along with increased or decreased mycorrhizal colonization of roots. Such effects, along with their duration, appear to be site- and (or) fire-specific, but are likely to be greater in the upper soil horizons. Where repeated burning occurs, the effects on soil fungal communities appear to be more pronounced with more frequent burning. Although fire may effect structural changes in soil fungal communities, the functional significance of such changes at the ecosystem level remains difficult to assess.
A computer approach to finding an optimal log landing location and analyzing influencing factors for ground-based timber harvesting
Authors: Contreras Marco , Chung Woodam
Published: May 2007

Locating a log landing is an important task in forest operations planning. Several methods have been developed to find an optimal landing location and compute a mean skidding distance, but they simplify harvest unit attributes and do not simultaneously consider multiple design factors influencing optimal landing locations. In this study, we introduce a computerized model developed to determine the optimal landing location for ground-based timber harvesting. Using raster-based GIS data, the model finds skid trails from stump to each of candidate landings and selects the best landing location that minimizes total skidding and spur road costs. The model is applied to several hypothetical harvest units with different terrain and harvest volume attributes to analyze the effects of design factors influencing optimal landing locations. Unit boundary shapes, volume distribution, the presence of obstacles, terrain conditions, and spur road construction are considered as influencing design factors.
Damage to Abies koreana seeds by soil-borne fungi on Mount Halla, Korea
Authors: Cho HyeKyoung , Miyamoto Toshizumi , Takahashi Kunihide , Hong SungGak , Kim JongJin
Published: May 2007

Abies koreana Wilson is an endemic tree species that is facing critical population declines in Korea. To identify factors affecting the natural regeneration of A. koreana, we examined the role of seed pathogens in the overwintering survival of seeds in natural seedbeds on Mount Halla, Korea. In September 2003, seeds of A. koreana were placed on seedbeds in the following three types of sites: Sasa dominated, shaded by rocks, or forest floor; seeds were then recovered from beneath the snow cover in April 2004 and were analyzed for the occurrence of harmful microfungi. Racodium therryanum Thuem. was the fungus most often isolated from retrieved seeds and was also the most detrimental of the eight fungal species tested in a pathogenicity trial. In vitro, R. therryanum caused a total loss of germination ability in A. koreana seeds at 0 °C after 100 days. The infection rate of R. therryanum was negatively correlated with the seed germination rate. The infection rate of R. therryanum was highest on the forest floor and increased with the duration of snow cover. The occurrence of R. therryanum was temporally restricted to the period of snow cover and spatially to the thick A0 soil layer on the forest floor. This study suggests that R. therryanum may be a significant factor inhibiting the natural regeneration of A. koreana at the seed stage.
Projected long-term productivity in Saskatchewan hybrid poplar plantations: weed competition and fertilizer effects
Authors: Welham Clive , Van Rees Ken , Seely Brad , Kimmins Hamish
Published: May 2007

An ecosystem management model was used to project total aboveground and belowground production in hybrid poplar plantations for two sites in Saskatchewan that were previously in agricultural production and that differed in their soil organic matter and nitrogen content (categorized as poor and rich sites). Stemwood production (the primary measure of treatment response) was always negatively affected by the competition that resulted when weeds were abundant; the effect was more severe on the poor than on the rich site. Stemwood biomass was greater when weed competition was low, but peak production declined over successive rotations on both sites, regardless of whether fertilizer was used. Fertilization always enhanced stemwood production but less so on the rich than on the poor site. A single fertilizer application in the second or seventh year after plantation establishment resulted in consistently higher stemwood production than midrotation fertilization (year 12). Fertilization was more beneficial to stemwood production when weed competition was high than when it was low. Low weed competition in conjunction with early fertilization produced the highest stemwood production. The simulations indicate that the relative benefit of a given management regime cannot be considered independently of the site nutrient status and the particular rotation.
Spatial effects of retention trees on mycorrhizas and biomass of Douglas-fir seedlings
Authors: Cline E. , Vinyard B. , Edmonds R.
Published: May 2007

Retention forestry places seedlings in proximity to residual trees, exposing seedlings to additional sources of ectomycorrhizal fungus (EMF) inoculum. To investigate this, Douglas-fir ( Pseudotsuga menziesii (Mirb.) Franco) seedlings were planted near (2–6 m) and far (16–30 m) from 44- to 72-year-old residual Douglas-fir trees in western Washington, USA. From 1998 through 2000, seedling shoot and root biomass was assessed and EMF taxa were identified using morphology and sequence analysis of internal transcribed spacer and large subunit ribosomal RNA genes. Seedlings near residual trees had significantly greater ectomycorrhiza (ECM) abundance (percent active ECM root tips), less necrotic root tips, and higher root to shoot biomass ratios. Seedlings near trees had a richness index of 4.1 EMF taxa per seedling and 42 total taxa compared with 3.5 taxa per seedling and 33 total taxa for seedlings far from trees. Proximity to residual trees may increase seedling ECM abundance and diversity.
Effects of local changes in active layer and soil climate on seasonal foliar nitrogen concentrations of three boreal forest shrubs
Authors: Rohrs-Richey Jennifer K. , Mulder Christa P.H.
Published: May 2007

Caribou Poker Creeks Research Watershed is a boreal forest watershed in Interior Alaska that is susceptible to regional warming and permafrost thaw. We measured seasonal foliar N concentrations of the black spruce understory shrubs, Vaccinium uliginosum L., Vaccinium vitis-idaea L., and Ledum palustre L. on north- and south-facing sides of the watershed. We predicted that the shrubs would respond to small-scale changes in active layer and soil climate, and we expected similar responses according to growth strategy (evergreen or deciduous). Overall, foliar N in shrubs was higher on warmer, drier soils with deep active layers: +7.9% N in V. uliginosum, +11.1% N in V. vitis-idaea, and +9.4% N in L. palustre. Each shrub had species-specific foliar N patterns that could not be categorized by growth strategy and were not well explained by soil climate or active layer. Leaf mineral nutrition is influenced by multiple processes, and foliar N was best explained by the combination of environmental variables operating at the study site. For Caribou Poker Creeks Research Watershed, we can expect increased N status of the black spruce understory along with continued climate warming, but changes cannot be predicted based on growth strategy.
Phytolith evidence for the absence of a prehistoric grass understory in a Jeffrey pine – mixed conifer forest in the Sierra San Pedro Mártir, Mexico
Authors: Evett Rand R. , Franco-Vizcaino Ernesto , Stephens Scott L.
Published: May 2007

Phytolith analysis was applied to several sites in a Jeffrey pine ( Pinus jeffreyi Grev. & Balf.) – mixed conifer forest in the Sierra San Pedro Mártir, Baja California, Mexico, to explore the hypothesis that the introduction of livestock in the late 18th century led to overgrazing of a prehistoric grass understory, resulting in changes to the prehistoric fire regime observed in the tree-ring fire-scar record. Stable soils in regions with extensive prehistoric grass cover retain a high concentration of total phytoliths and high percentage of grass phytoliths, regardless of historic vegetation changes. Phytoliths extracted from soil samples collected from several sites in the Sierra San Pedro Mártir revealed total phytolith concentrations in forest soils were generally <0.5% by mass, with most <0.1%, whereas grass phytoliths were generally <10% of the total, values consistent with the interpretation of a forest with sparse grass cover in the understory. Phytolith evidence suggests that there was minimal grass available for grazing in prehistoric Sierra San Pedro Mártir forests; overgrazing a grass understory was probably not a major driver of changes in the prehistoric fire regime.
Comparing modern and past fire regimes to assess changes in prehistoric lightning and anthropogenic ignitions in a Jeffrey pine – mixed conifer forest in the Sierra San Pedro Mártir, Mexico
Authors: Evett Rand R. , Franco-Vizcaino Ernesto , Stephens Scott L.
Published: May 2007

Fire histories of Jeffrey pine ( Pinus jeffreyi Grev. & Balf.) – mixed conifer forests in the Sierra San Pedro Mártir, Baja California, Mexico, recently described through analysis of 300 years of tree-ring fire-scars, indicate there have been four distinct fire-regime periods based on fire frequency and size. We used modern lightning and fire data to assess whether the current lightning regime could have supported the prehistoric fire regime. Although there are several sources of uncertainty, the present lightning regime, concentrated in the summer with little spring activity, may be insufficient to support the high number and spring seasonality of fires recorded during some periods in the past. Changes in the ignition regime recorded during the past 300 years could have been due to anthropogenic and (or) climatic factors; available evidence suggests periods of frequent fire were dominated by anthropogenic ignitions.
Slash burning, faunal composition, and nutrient dynamics in a Eucalyptus grandis plantation in South AfricaThis article is one of a selection of papers published in the Special Forum on Towards Sustainable Forestry — The Living Soil: Soil Biodiversity and Ecosystem Function.
Authors: Nadel R.L. , Scholes M.C. , Byrne M.J.
Published: May 2007

The sustainability of exotic commercial plantations is dependent on the conservation of soil nutrients, especially on the ancient, leached soils of the tropics, particularly when limited fertilization is practiced. In Eucalyptus grandis W. Hill ex Maid. plantations in South Africa, the site is usually burned following harvest and prior to replanting, potentially causing a disruption of soil faunal function and losses of nutrients associated with burning and removal of slash residues. The aim was to study the effect of fire on nutrient dynamics and invertebrate faunal composition. The in situ nitrogen and phosphorus mineralization rates and invertebrate faunal composition were measured in six randomly located plots — three burned and three unburned — prior to and after a low-intensity fire. Results indicate that within the burned plots, phosphorus availability was enhanced 10-fold within the first month following the fire. Invertebrate faunal diversity was low both prior to and after burning, with ants constituting the highest number. Invertebrate faunal composition was more markedly influenced by season than by the fire, with millipedes present in the majority of plots in spring and ants dominating in summer.
SYNCHRONIZED FLOW AND PHASE SEPARATION IN A TWO-LANE CELLULAR AUTOMATON MODEL
Authors: YUAN YAO-MING , JIANG RUI , WU QING-SONG , WANG RUILI
Published: May 2007

This paper extends a cellular automaton model, named modified comfortable driving (MCD) model, to a two-lane roadway. A symmetric lane-changing rule set has been proposed (Set I). The fundamental diagram, the lane-changing frequency and space-time plots are presented. It is found that for the two-lane model, there exists a density range in which phase separation between synchronized flow and wide-moving jams on one lane, and between light synchronized flow and heavy synchronized flow on the other lane, can be maintained for quite long periods of time. In this density range, (i) the outflow from jams is synchronized flow; (ii) wide moving jams are sparse. These are consistent with the empirical observation. We also investigate a slightly different lane-changing rule Set II in which stopped vehicles are not allowed to change lane. It is shown that in this case, the phase separation, between free flow and wide moving jams on one lane and between free flow and heavy synchronized flow on the other lane, can be maintained for sufficiently long periods of time. Consequently, the flux is enhanced comparing to that of rule Set I.
BASIC PROPERTIES AND CHAOTIC SYNCHRONIZATION OF COMPLEX LORENZ SYSTEM
Authors: MAHMOUD GAMAL M. , Al-KASHIF M. A. , ALY SHABAN A.
Published: May 2007

This paper aims at studying the basic properties and chaotic synchronization of complex Lorenz system: [Formula: see text] where α, γ, β are positive (real or complex) parameters, x and y are complex variables, z is a real variable, an overbar denotes complex conjugate variable and dots represent derivatives with respect to time. This system arises in many important applications in physics, for example, in laser physics and rotating fluids dynamics.

Numerically we show that this system is a chaotic system and exhibits chaotic attractors. The necessary conditions for system (⋆) to generate chaos are obtained. Analytical and numerical calculations are presented to achieve synchronization. Active control technique is used to synchronize chaotic attractors of equations (⋆).
A NEW NUMERICAL APPROACH FOR FIRE SIMULATION
Authors: CHEN SHENG , LIU ZHAOHUI , HE ZHU , ZHANG CHAO , TIAN ZHIWEI , ZHENG CHUGUANG
Published: May 2007

It is an urgent task to adopt/develop new numerical methods in fire research because of the intrinsic disadvantages of traditional numerical methods, such as in complicated geometries treatment, computational efficiency on parallel computers. The outstanding features of the lattice Boltzmann method (LBM) has emerged which is a very promising alternative in this field. Unfortunately, until recently the LBM could not be employed in fire research due to its inherent defects in combustion simulation. In order to extend the LBM into fire research, a novel LB model for fire simulation is designed in this study. Besides the intrinsic advantages of the standard LBM, this model shows improved numerical stability and can cover temperature ratio of more than one order of magnitude. The model is validated through a benchmark test "coflow methane-air diffusion flame". Furthermore, because little attention has been paid to the effect of the interaction between the inlet boundary and the interior of the flow field on stability of the computation and the quality of the solution, therefore in this study we also discuss this problem in detail to bridge this gap.
THE PARITY GATE: FROM QUANTUM NETWORKS TO ENTANGLEMENT GENERATION
Authors: IONICIOIU RADU
Published: May 2007

It has been shown recently that parity measurement is an efficient entangler for fermions and hence is a universal resource for fermionic quantum computing with linear elements. In this article, we investigate several properties of the parity P-gate. We construct a simple quantum network model for the P-gate and derive gate identities for it. Finally, we examine entanglement generation using parity measurements.
PHASE CONJUGATE MIRRORS, ONE WAY VELOCITY OF LIGHT AND MEASURE OF ANTI-COHERENCE
Authors: GARUCCIO AUGUSTO
Published: May 2007

The behavior of phase-conjugate mirrors (PCM) is discussed and a Michelson interferometer with a PCM is described and discussed. This interferometer has been proposed to be used to test the intrinsic non-locality of quantum mechanics and to measure the one-way velocity of light. Moreover, this device can be used in order to measure the intrinsic anticoherence of light.
Constitutive and inducible thymic stromal lymphopoietin expression in human airway smooth muscle cells: role in chronic obstructive pulmonary disease
Authors: Zhang Keqin , Shan Lianyu , Rahman Muhammad Sahidu , Unruh Helmut , Halayko Andrew J. , Gounni Abdelilah Soussi
Published: May 2007

Thymic stromal lymphopoietin (TSLP) is a novel cytokine that triggers dendritic cell-mediated T helper (Th)-2 inflammatory responses. Previous studies have demonstrated that human airway smooth muscle cells (HASMC) play a critical role in initiating or perpetuating airway inflammation by producing chemokines and cytokines. In this study, we first evaluated the expression of TSLP in primary HASMC and investigated how proinflammatory cytokines (TNF-α and IL-1β) and Th-2 cytokines (IL-4, IL-9) regulate TSLP production from HASMC. TSLP mRNA and protein were assessed by real-time RT-PCR, ELISA, and immunofluorescence from primary HASMC cultures. Primary HASMC express constitutive level of TSLP. Incubation of HASMC with IL-1 or TNF-α resulted in a significant increase of TSLP mRNA and protein release from HASMC. Furthermore, combination of IL-1β and TNF-α has an additive effect on TSLP release by HASMC. Primary HASMC pretreated with inhibitors of p38 or p42/p44 ERK MAPK, but not phosphatidylinositol 3-kinase, showed a significant decrease in TSLP release on IL-1β and TNF-α treatment. Furthermore, TSLP immunoreactivity was present in ASM bundle from chronic obstructive pulmonary disease (COPD) and to lesser degree in normal subjects. Taken together, our data provide the first evidence of IL-1β- and TNF-α-induced TSLP expression in HASMC via (p38, p42/p44) MAPK signaling pathways. Our results raise the possibility that HASMC may play a role in COPD airway inflammation via TSLP-dependent pathway.
Postpneumonectomy lung expansion elicits hypoxia-inducible factor-1α signaling
Authors: Zhang Quiyang , Bellotto Dennis J. , Ravikumar Priya , Moe Orson W. , Hogg Richard T. , Hogg Deborah C. , Estrera Aaron S. , Johnson Robert L. , Hsia Connie C. W.
Published: May 2007

We ( 42 ) previously reported differential regulation of hypoxia-inducible factors (HIF-1α, -2α, and -3α) mRNA in canine lungs during normal maturation and postpneumonectomy (PNX) compensatory growth in the absence of overt hypoxia. To test the hypothesis that lung expansion activates HIF signaling, we replaced the right lung of six adult foxhounds with inflated custom-shaped silicone prosthesis to keep the mediastinum in the midline and minimize lateral expansion of the remaining lung. After 3 wk of recovery and stabilization of perfusion, the prosthesis was acutely deflated in three animals, causing the remaining lung to expand by 114%. In three other animals, the prosthesis remained inflated. Three days following deflation, we observed significant elevation in the mRNA and nuclear protein levels of HIF-1α (∼60%) as well as activation of its transcriptional regulator, the serine/threonine protein kinase B (phospho-Akt-to-total Akt ratio, 124%), and the mRNA and protein levels of its downstream targets, erythropoietin receptor (71–183%) as well as VEGF (33–58%) compared with the pre-PNX control lung from the same animal. The mRNA of HIF-2α, HIF-3α, and VEGF receptors did not change with acute deflation. We conclude that in vivo lung expansion by post-PNX deflation of space-occupying prosthesis elicits coordinated activation of HIF-1α signaling in adult lungs. This pathway could play an important role in mediating lung growth and remodeling during maturation and post-PNX compensation.
Shikonin circumvents cancer drug resistance by induction of a necroptotic death
Authors: Han Weidong , Li Ling , Qiu Shuang , Lu Qinghua , Pan Qiangrong , Gu Ying , Luo Jianhong , Hu Xun
Published: May 2007

Defect in apoptotic signaling and up-regulation of drug transporters in cancer cells significantly limits the effectiveness of cancer chemotherapy. We propose that an agent inducing non-apoptotic cell death may overcome cancer drug resistance and showed that shikonin, a naturally occurring naphthoquinone, induced a cell death in MCF-7 and HEK293 distinct from apoptosis and characterized with (a) a morphology of necrotic cell death; (b) loss of plasma membrane integrity; (c) loss of mitochondrial membrane potentials; (d) activation of autophagy as a downstream consequence of cell death, but not a contributing factor; (e) elevation of reactive oxygen species with no critical roles contributing to cell death; and (f) that the cell death was prevented by a small molecule, necrostatin-1, that specifically prevents cells from necroptosis. The characteristics fully comply with those of necroptosis, a basic cell-death pathway recently identified by Degterev et al. with potential relevance to human pathology. Furthermore, we proved that shikonin showed a similar potency toward drug-sensitive cancer cell lines (MCF-7 and HEK293) and their drug-resistant lines overexpressing P-glycoprotein, Bcl-2, or Bcl-xL, which account for most of the clinical cancer drug resistance. To our best knowledge, this is the first report to document the induction of necroptosis by a small molecular compound to circumvent cancer drug resistance. [Mol Cancer Ther 2007;6(5):1641–9]
Enhanced tumor cell kill by combined treatment with a small-molecule antagonist of mouse double minute 2 and adenoviruses encoding p53
Authors: Graat Harm C.A. , Carette Jan E. , Schagen Frederik H.E. , Vassilev Lyubomir T. , Gerritsen Winald R. , Kaspers Gertjan J.L. , Wuisman Paul I.J.M. , van Beusechem Victor W.
Published: May 2007

Strategies to treat cancer by restoring p53 tumor suppressor functions are being actively investigated. These approaches range from expressing an exogenous p53 gene in p53 mutant cancers to antagonizing a p53 inhibitor in p53 wild-type (WT) cancer cells. In addition, exogenous p53 is used to strengthen the anticancer efficacy of oncolytic adenoviruses. Many cancers express high levels of the major negative regulator of p53, mouse double minute 2 (MDM2) protein. Recently, a novel class of highly potent and specific MDM2 antagonists, the Nutlins, was identified. We envisioned that Nutlins could protect both endogenous and exogenous p53 from MDM2-mediated inactivation. We therefore investigated treating human cancer cells with a combination of adenovirus-mediated p53 gene therapy and Nutlin. Combination treatment resulted in broadly effective cell kill of p53 WT and p53-negative cancer cells. Cytotoxicity was associated with profound cell cycle checkpoint activation and apoptosis induction. We also tested Nutlin in combination with oncolytic adenoviruses. Nutlin treatment accelerated viral progeny burst from oncolytic adenovirus-infected cancer cells and caused an estimated 10- to 1,000-fold augmented eradication of p53 WT cancer cells. These findings suggest that Nutlins are promising compounds to be combined with p53 gene therapy and oncolytic virotherapy for cancer. [Mol Cancer Ther 2007;6(5):1552–61]
Rad51 overexpression contributes to chemoresistance in human soft tissue sarcoma cells: a role for p53/activator protein 2 transcriptional regulation
Authors: Hannay Jonathan A.F. , Liu Juehui , Zhu Quan-Sheng , Bolshakov Svetlana V. , Li Lan , Pisters Peter W.T. , Lazar Alexander J.F. , Yu Dihua , Pollock Raphael E. , Lev Dina
Published: May 2007

We investigated whether Rad51 overexpression plays a role in soft tissue sarcoma (STS) chemoresistance as well as the regulatory mechanisms underlying its expression. The studies reported here show that Rad51 protein is overexpressed in a large panel of human STS specimens. Human STS cell lines showed increased Rad51 protein expression, as was also observed in nude rat STS xenografts. STS cells treated with doxorubicin exhibited up-regulation of Rad51 protein while arrested in the S-G2 phase of the cell cycle. Treatment with anti-Rad51 small interfering RNA decreased Rad51 protein expression and increased chemosensitivity to doxorubicin. Because we previously showed that reintroduction of wild-type p53 (wtp53) into STS cells harboring a p53 mutation led to increased doxorubicin chemosensitivity, we hypothesized that p53 participates in regulating Rad51 expression in STS. Reintroduction of wtp53 into STS cell lines resulted in decreased Rad51 protein and mRNA expression. Using luciferase reporter assays, we showed that reconstitution of wtp53 function decreased Rad51 promoter activity. Deletion constructs identified a specific Rad51 promoter region containing a p53-responsive element but no p53 consensus binding site. Electrophoretic mobility shift assays verified activator protein 2 (AP2) binding to this region and increased AP2 binding to the promoter in the presence of wtp53. Mutating this AP2 binding site eliminated the wtp53 repressive effect. Furthermore, AP2 knockdown resulted in increased Rad51 expression. In light of the importance of Rad51 in modulating STS chemoresistance, these findings point to a potential novel strategy for molecular-based treatments that may be of relevance to patients burdened by STS. [Mol Cancer Ther 2007;6(5):1650–60]
Transactivator of transcription–tagged cell cycle and apoptosis regulatory protein-1 peptides suppress the growth of human breast cancer cells in vitro and in vivo
Authors: Zhang Liyue , Levi Edi , Majumder Pralay , Yu Yingjie , Aboukameel Amro , Du Jianhua , Xu Hu , Mohammad Ramzi , Hatfield James S. , Wali Anil , Adsay Volkan , Majumdar Adhip P.N. , Rishi Arun K.
Published: May 2007

Deregulated signaling by the epidermal growth factor receptor family of proteins is encountered in human malignancies including breast cancer. Cell cycle and apoptosis-regulatory protein-1 (CARP-1), a novel, perinuclear phosphoprotein, is a regulator of apoptosis signaling by epidermal growth factor receptors. CARP-1 expression is diminished in human breast cancers, and correlates inversely with human breast cancer grades which could be attributed to increased methylation. The expression of CARP-1, on the other hand, interferes with the ability of human breast cancer cells to invade through the matrigel-coated membranes, to form colonies in the soft agar, and to grow as s.c. tumors in severe combined immunodeficiency (SCID) mice. To test whether CARP-1 is a suppressor of human breast cancer growth, we generated transactivator of transcription (TAT)–tagged CARP-1 peptides. Treatment of human breast cancer cells with affinity purified, TAT-CARP-1 1–198, 197–454, and 896–1150 peptides caused inhibition of human breast cancer cell proliferation and elevated apoptosis. In contrast, TAT-tagged enhanced green fluorescent protein or CARP-1 (1–198Y192/F) peptide failed to inhibit cell proliferation or induce apoptosis. Apoptosis by CARP-1 peptides, with the exception of CARP-1 (1–198Y192/F), involves the activation of p38 stress-activated protein kinase and caspase-9. Moreover, administration of TAT-CARP-1 (1–198), but not TAT-tagged enhanced green fluorescent protein or TAT-CARP-1 (1–198Y192/F), inhibits growth of human breast cancer cell–derived tumor xenografts in SCID mice. We conclude that CARP-1 is a suppressor of human breast cancer growth, and its expression is diminished in tumors, in part, by methylation-dependent silencing. [Mol Cancer Ther 2007;6(5):1661–72]
Increased expression of cyclin B1 sensitizes prostate cancer cells to apoptosis induced by chemotherapy
Authors: Gomez Lourdes A. , de las Pozas Alicia , Reiner Teresita , Burnstein Kerry , Perez-Stable Carlos
Published: May 2007

Chemotherapeutic drugs ideally should take advantage of the differences between transformed and normal cells and induce apoptosis only in cancer cells. One such difference may be the overexpression of cyclin B1 protein in cancer cells, which is required for the proper progression through mitosis. Previously, we showed that treatment of human prostate cancer cells with 2-methoxyestradiol (2-ME) or docetaxel results in an accumulation of cyclin B1 protein and an increase in cyclin B1 kinase activity, followed by induction of apoptotic cell death. Inhibition of cyclin B1 kinase lowers apoptosis induced by 2-ME and docetaxel. In this study, we established a positive correlation between cyclin B1 protein and apoptosis induced by chemotherapy in prostate cancer cells. There is minimal cyclin B1 and induction of apoptosis by chemotherapy in nontransformed cells. LNCaP and PC-3 prostate cancer cells stably overexpressing cyclin B1 are more sensitive to apoptosis induced by chemotherapy. LNCaP cells expressing cyclin B1 small interfering RNA to lower cyclin B1 protein or dominant negative cyclin-dependent kinase 1 to inhibit cyclin B1 kinase show a decrease in apoptosis. Increased sensitivity to apoptosis by overexpression of cyclin B1 may be due to lower Bcl-2, higher p53, and decreased neuroendocrine differentiation. We suggest that a cancer-specific mechanism whereby 2-ME and docetaxel may exert anti–prostate cancer activity is the deregulated activation of cyclin B1 kinase, leading to the induction of apoptotic cell death. Our results also suggest that higher levels of cyclin B1 in prostate cancer cells may be a good prognostic marker for chemotherapy. [Mol Cancer Ther 2007;6(5):1534–43]
Mitochondria-mediated apoptosis by diallyl trisulfide in human prostate cancer cells is associated with generation of reactive oxygen species and regulated by Bax/Bak
Authors: Kim Young-Ae , Xiao Dong , Xiao Hui , Powolny Anna A. , Lew Karen L. , Reilly Megan L. , Zeng Yan , Wang Zhou , Singh Shivendra V.
Published: May 2007

Garlic constituent diallyl trisulfide (DATS) inhibits growth of cancer cells in vitro and in vivo by causing apoptosis, but the sequence of events leading to cell death is not fully understood. We now show that DATS treatment triggers mitochondria-mediated apoptosis program in human prostate cancer cells (LNCaP, LNCaP-C81, LNCaP-C4-2) irrespective of their androgen responsiveness. Interestingly, a normal prostate epithelial cell line (PrEC) is significantly more resistant to apoptosis induction by DATS compared with prostate cancer cells. The DATS-induced apoptosis in LNCaP cells correlated with the collapse of mitochondrial membrane potential, modest increase in protein level of Bak, and down-regulation of Bcl-2 and Bcl-xL protein levels. The DATS-induced apoptosis was significantly attenuated by knockdown of Bax and Bak proteins, but not by ectopic expression of either Bcl-2 or Bcl-xL. The DATS treatment caused generation of reactive oxygen species (ROS) in LNCaP cells, but not in PrEC, which was attenuated by pretreatment with antioxidant N-acetylcysteine. The N-acetylcysteine pretreatment conferred significant protection against DATS-mediated disruption of the mitochondrial membrane potential and apoptosis. In conclusion, the present study reveals that the mitochondria-mediated cell death by DATS is associated with ROS generation and regulated by Bax/Bak but independent of Bcl-2 or Bcl-xL. [Mol Cancer Ther 2007;6(5):1599–609]
Inhibition of topoisomerase IIα and G2 cell cycle arrest by NK314, a novel benzo[c]phenanthridine currently in clinical trials
Authors: Guo Lei , Liu Xiaojun , Nishikawa Kiyohiro , Plunkett William
Published: May 2007

NK314 is a novel synthetic benzo[c]phenanthridine alkaloid that has recently entered clinical trials as an antitumor compound, based on impressive activities in preclinical models. The present investigations were directed at determining the mechanism of action of this agent. NK314 induced significant G2 cell cycle arrest in several cell lines, independent of p53 status, suggesting the existence of a common mechanism of checkpoint activation. The Chk1-Cdc25C-Cdk1 G2 checkpoint pathway was activated in response to 100 nmol/L NK314 in ML-1 human acute myeloid leukemia cells. This was associated with the phosphorylation of the histone variant H2AX, an action that was predominant in the G2 population, suggesting that double-strand DNA breaks caused cells to activate the checkpoint pathway. Double-strand DNA breaks were visualized as chromosomal aberrations when the G2 checkpoint was abrogated by 7-hydroxystaurosporine. In vitro assays showed that NK314 inhibited the ability of topoisomerase IIα to relax supercoiled DNA and trapped topoisomerase IIα in its cleavage complex intermediate. CEM/VM1 cells, which are resistant to etoposide due to mutations in topoisomerase IIα, were cross-resistant to NK314. However, CEM/C2 cells, which are resistant to camptothecin due to mutations in topoisomerase I, retained sensitivity. These findings support the conclusion that the major mechanism of NK314 is to inhibit topoisomerase IIα, an action that leads to the generation of double-strand DNA breaks, which activate the G2 DNA damage checkpoint pathway. [Mol Cancer Ther 2007;6(5):1501–8]
ZD1839 induces p15INK4b and causes G1 arrest by inhibiting the mitogen-activated protein kinase/extracellular signal–regulated kinase pathway
Authors: Koyama Makoto , Matsuzaki Youichirou , Yogosawa Shingo , Hitomi Toshiaki , Kawanaka Mayumi , Sakai Toshiyuki
Published: May 2007

Inactivation of the retinoblastoma protein pathway is the most common abnormality in malignant tumors. We therefore tried to detect agents that induce the cyclin-dependent kinase inhibitor p15INK4b and found that ZD1839 (gefitinib, Iressa) could up-regulate p15INK4b expression. ZD1839 has been shown to inhibit cell cycle progression through inhibition of signaling pathways such as phosphatidylinositol 3′-kinase-Akt and mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) cascades. However, the mechanism responsible for the differential sensitivity of the signaling pathways to ZD1839 remains unclear. We here showed that ZD1839 up-regulated p15INK4b, resulting in retinoblastoma hypophosphorylation and G1 arrest in human immortalized keratinocyte HaCaT cells. p15INK4b induction was caused by MAPK/ERK kinase inhibitor (PD98059), but not by Akt inhibitor (SH-6, Akt-III). Moreover, mouse embryo fibroblasts lacking p15INK4b were resistant to the growth inhibitory effects of ZD1839 compared with wild-type mouse embryo fibroblasts. Additionally, the status of ERK phosphorylation was related to the antiproliferative activity of ZD1839 in human colon cancer HT-29 and Colo320DM cell lines. Our results suggest that induction of p15INK4b by inhibition of the MAPK/ERK pathway is associated with the antiproliferative effects of ZD1839. [Mol Cancer Ther 2007;6(5):1579–1587]
Core Components of Cardiac Rehabilitation/Secondary Prevention Programs: 2007 Update
Authors: Balady Gary J. , Williams Mark A. , Ades Philip A. , Bittner Vera , Comoss Patricia , Foody JoAnne M. , Franklin Barry , Sanderson Bonnie , Southard Douglas
Published: May 2007

The American Heart Association and the American Association of Cardiovascular and Pulmonary Rehabilitation recognize that all cardiac rehabilitation/secondary prevention programs should contain specific core components that aim to optimize cardiovascular risk reduction, foster healthy behaviors and compliance to these behaviors, reduce disability, and promote an active lifestyle for patients with cardiovascular disease. This update to the previous statement presents current information on the evaluation, interventions, and expected outcomes in each of the core components of cardiac rehabilitation/secondary prevention programs, in agreement with the 2006 update of the American Heart Association/American College of Cardiology Secondary Prevention Guidelines, including baseline patient assessment, nutritional counseling, risk factor management (lipids, blood pressure, weight, diabetes mellitus, and smoking), psychosocial interventions, and physical activity counseling and exercise training.
Synoptic Modeling in the Eastern Arabian Sea during the Southwest Monsoon Using Upwelling Feature Models
Authors: Shaji C. , Gangopadhyay A.
Published: May 2007

Hydrographic observations along the western coast of India during the southwest (SW) monsoon season reveal upwelling in the equatorward surface flow and downwelling below the thermocline with a weak poleward undercurrent. Observations made previously during the peak of the SW monsoon in boreal summer showed that upwelling temperatures are much cooler (<23°C) than compared to the available climatology data in this region. A feature modeling technique is used to describe the temperature distribution associated with the West India Coastal Current (WICC) upwelling. This kind of formulation captures the upwelling and downwelling associated with the WICC reasonably well, though it requires the specification of a few observed offshore and nearshore temperature profiles. The temperature–salinity relationship from the Levitus climatology data is further used to obtain a compatible salinity distribution for the feature model. The efficiency of this feature model is further validated via a dynamical model simulation: here, the temperature–salinity feature model profiles are objectively melded with the Levitus climatology to create the synoptic initial condition. The WICC’s local circulation and simulated upwelling temperatures are more realistic in the dynamical model simulation with the feature model than in a simulation that does not utilize the upwelling feature model. The advantage of the feature modeling technique used herein is that it provides additional or new information that the OGCMs or prognostic ocean models can adapt to improve the latter’s initial condition and for synoptic forecasting. Furthermore, the generalized formulation of the upwelling feature model developed here may be used in other regional coastal oceans as well.
Field Verification of ADCP Surface Gravity Wave Elevation Spectra
Authors: Hoitink A. J. F. , Peters H. C. , Schroevers M.
Published: May 2007

Acoustic Doppler current profilers (ADCPs) can measure orbital velocities induced by surface gravity waves, yet the ADCP estimates of these velocities are subject to a relatively high noise level. The present paper introduces a linear filtration technique to significantly reduce the influence of noise and turbulence from energy spectra of combined orbital velocity measurements. Data were collected in 13-m-deep water with a 1.2-MHz ADCP sampling in mode 12, where a collocated wave buoy was used for verification. The surface elevation spectra derived from the filtrated and nonfiltrated measurements were compared with corresponding wave buoy spectra. In the frequency range between 0.12 and 0.5 Hz, ADCP- and wave-buoy-derived spectral estimates matched very well, even without applying the filtration technique. At frequencies below 0.12 Hz, the ADCP-derived surface elevation spectra are biased, caused by a depth-varying excess of spectral energy density in the measured orbital velocities, peaking at middepth. Internal waves may provide an explanation for the energy excess, as the experiment was conducted in the region of influence of the Rhine freshwater plume. Alternatively, infragravity waves may be the cause of the depth variation of low-frequency spectral energy density.
Performance of Quality Assurance Procedures on Daily Precipitation
Authors: You Jinsheng , Hubbard Kenneth G. , Nadarajah Saralees , Kunkel Kenneth E.
Published: May 2007

The search for precipitation quality control (QC) methods has proven difficult. The high spatial and temporal variability associated with precipitation data causes high uncertainty and edge creep when regression-based approaches are applied. Precipitation frequency distributions are generally skewed rather than normally distributed. The commonly assumed normal distribution in QC methods is not a good representation of the actual distribution of precipitation and is inefficient in identifying the outliers. This paper first explores the use of a single gamma distribution, fit to all precipitation data, in a quality assurance test. A second test, the multiple intervals gamma distribution (MIGD) method, is introduced. It assumes that meteorological conditions that produce a certain range in average precipitation at surrounding stations will produce a predictable range at the target station. The MIGD bins the average of precipitation at neighboring stations; then, for the events in a specific bin, an associated gamma distribution is derived by fit to the same events at the target station. The new gamma distributions can then be used to establish the threshold for QC according to the user-selected probability of exceedance. This paper also explores a test (Q test) for precipitation, which uses a metric based on comparisons with neighboring stations. The performance of the three approaches is evaluated by assessing the fraction of “known” errors that can be identified in a seeded error dataset. The single gamma distribution and Q-test approach were found to be relatively efficient at identifying extreme precipitation values as potential outliers. However, the MIGD method outperforms the other two QC methods. This method identifies more seeded errors and results in fewer type I errors than the other methods. It will be adopted in the Applied Climatic Information System (ACIS) for precipitation quality control.
On the Equivalence of Dual-Wavelength and Dual-Polarization Equations for Estimation of the Raindrop Size Distribution
Authors: Meneghini Robert , Liao Liang
Published: May 2007

For air- and spaceborne weather radars, which typically operate at frequencies of 10 GHz and above, attenuation correction is usually an essential part of any rain estimation procedure. For ground-based radars, where the maximum range within the precipitation is usually much greater than that from air- or spaceborne radars, attenuation correction becomes increasingly important at frequencies above about 5 GHz. Although dual-polarization radar algorithms rely on the correlation between raindrop shape and size, while dual-wavelength weather radar algorithms rely primarily on non-Rayleigh scattering at the shorter wavelength, the equations for estimating parameters of the drop size distribution (DSD) are nearly identical in the presence of attenuation. Many of the attenuation correction methods that have been proposed can be classified as one of two types: those that employ a kZ (specific attenuation–radar reflectivity factor) relation, and those that use an integral equation formalism where the attenuation is obtained from the DSD parameters at prior gates, either stepping outward from the radar or inward toward the radar from some final range gate. The similarity is shown between the dual-polarization and dual-wavelength equations when either the kZ or the integral equation formulation is used. Differences between the two attenuation correction procedures are illustrated for simulated measurements from an X-band dual-polarization radar.
STRAT: An Automated Algorithm to Retrieve the Vertical Structure of the Atmosphere from Single-Channel Lidar Data
Authors: Morille Y. , Haeffelin M. , Drobinski P. , Pelon J.
Published: May 2007

Today several lidar networks around the world provide large datasets that are extremely valuable for aerosol and cloud research. Retrieval of atmospheric constituent properties from lidar profiles requires detailed analysis of spatial and temporal variations of the signal. This paper presents an algorithm called Structure of the Atmosphere (STRAT), which is designed to retrieve the vertical distribution of cloud and aerosol layers in the boundary layer and through the free troposphere and to identify near-particle-free regions of the vertical profile and the range at which the lidar signal becomes too attenuated for exploitation, from a single lidar channel. The paper describes each detection method used in the STRAT algorithm and its application to a tropospheric backscatter lidar operated at the SIRTA observatory, in Palaiseau, 20 km south of Paris, France. STRAT retrievals are compared to other means of layer detection and classification; retrieval performances and uncertainties are discussed.
Comparison of Plotting Methods for Solar Radiometer Calibration
Authors: Adler-Golden S. M. , Slusser J. R.
Published: May 2007

An alternative formulation of the Langley plot relating observed solar irradiance, extraterrestrial solar irradiance, and air mass has been suggested to potentially improve radiometer calibration accuracy. In this study, results from the traditional and alternative plotting methods are compared using both simulated and measured data. The simulations indicate that their relative accuracies depend on the time scale of the atmospheric extinction fluctuations. The two methods are found to be essentially equivalent with the measured data.