bluuebunny/crossref_metadata_2025 huggingface dataset:
NEMATODE (HETERODERA SCHACHTII) RESISTANCE AND MEIOSIS IN DIPLOID PLANTS FROM INTERSPECIFIC BETA VULGARIS × B. PROCUMBENS HYBRIDS
Authors: Savitsky Helen
Published: August 2008

Three diploid nematode-resistant plants derived from hybrids between Beta vulgaris L. and B. procumbens Chr. Sm. were crossed with diploid nematode-susceptible plants. The rates of resistance transmission from the F1 hybrids to the F2 varied from 7 to 27%. The transmission rate of F2 plants derived from F1 plants with transmission rates over 20% averaged 20.9%. The rate for F2 plants derived from F1 plants with transmission rates of 10% or lower averaged 11.3%. In diploid plants nematode resistance was transmitted through the pollen at lower frequencies than through egg cells. Transmission through female gametes varied from 11.0 to 31.4% and through male gametes of the same plants from 0 to 19.7%. In some pollen mother cells (PMCs) of diploid nematode-resistant plants meiosis was normal and gametes derived from these cells transmitted resistance to the next generation. Abnormalities were observed in other PMCs, including the detachment of the B. procumbens segment from the translocated chromosome, the formation of bridges, and the lagging of broken translocated chromosomes. The inadequate transmission of resistance was caused by a loss of the B. procumbens segment in some B. vulgaris bivalents.
SEX CHROMOSOME DIFFERENTIATION: AN INTERMEDIATE STAGE IN A LIZARD
Authors: Bull James
Published: August 2008

Sex chromosomes of the lizard, Cnemidophorus tigris (Baird and Girard), were analyzed in mitotic and meiotic cell divisions using C-band and G-band staining techniques. The X and Y are homologous along most of their lengths but do not crossover in the medial portion of the bivalent, where their centromeres lie. In this region the X and Y differ in centric position and heterochromatin. The similarities of the X and Y in C. tigris contrast to sex chromosomes in other animals, and probably represent an early stage of differentiation.
RELATIONSHIP OF CARTHAMUS LEUCOCAULOS TO OTHER CARTHAMUS SPECIES (COMPOSITAE)
Authors: Estilai A. , Knowles P. F.
Published: August 2008

Carthamus leucocaulos Sibth. &Sm., with n = 10, was found to be closely related to other species of the genus with the same chromosome number, in spite of its distinctive morphological appearance. Like other species with n = 10, it crossed readily with C. divaricatus Beg. et Vacc. (n = 11), giving a fertile hybrid. It was distantly related to C. nitidus Boiss. (n = 12), a species morphologically similar to C. leucocaulos. Relationships to other species were studied and discussed.
Acupuncture Analgesia: A Review of Its Mechanisms of Actions
Authors: Lin Jaung-Geng , Chen Wei-Liang
Published: August 2008

The mechanism of acupuncture analgesia (AA) has been widely explored since the 1970s. Early studies investigated the relationship between acupuncture and endogenous opiates (β-endorphin, enkephalin, endomorphin and dynorphin). Before the 1990s, most experts agreed on the concept that in normal animal models, lower frequency electroacupuncture (EA) stimulates the release of β-endorphin, enkephalin and endomorphin, which in turn activates the μ- and δ-opioid receptors, and that higher frequency EA stimulates dynorphin which activates the κ-opioid receptor. Besides endogenous opiates, our studies have focused on serotonin. The serotoninergic descending inhibitory pathway is suggested to be an important mechanism of acupuncture analgesic, collaborating with endogenous opiates. Many efforts have been made to clarify these mechanisms, but to date no satisfactory consensus has been reached. In the late 1990s, researchers began to focus on the different analgesic effects of EA between normal and hyperalgesic animal models. Published data from these studies imply that normal and hyperalgesic animals respond differently to EA. Results from experiments on the anti-hyperalgesia effect of EA have raised a new issue about the influences of EA on receptors to excitatory amino acid in the spinal cord level. Results from various studies have shown that these receptors play a role in the mechanism of AA. Recently, research on the autonomic nervous system (ANS) seem to indicate its connection with acupuncture. The inflammatory reflex (via the ANS) might be a crucial part of anti-hyperalgesia elicited by acupuncture, and this reflex, which regulates the immune system in the organism, can elucidate not only the mechanism of AA but also the mechanism of acupuncture applied to other inflammatory conditions. Innovation of functional image study enables us to analyze the responses of cortex on living human body to acupuncture. However, results of these experiments are still controversial. After 30 years of acupuncture research, there are still many puzzles left to be solved regarding the mechanism of AA.
Effects of 14-Week Tai Ji Quan Exercise on Metabolic Control in Women with Type 2 Diabetes
Authors: Zhang Ying , Fu Frank H.
Published: August 2008

The present study investigated the effects of 14 weeks of practicing Tai Ji Quan (TJQ) on metabolic control and lipid metabolism in women with type 2 diabetes. Twenty Beijing female residents (57.4 ± 6.2 years) were recruited and were randomly assigned to either the TJQ training or the control group. In the TJQ group, the exercise duration was 1 hour per day and 5 days a week for 14 weeks. FPG, GSP, FPI, TC, HDL-C, LDL-C, TG, resting blood pressures and heart rate were measured before and after the 14 weeks in the 2 groups. It was found that after 14 weeks, the TJQ group had significantly lower FPG, GSP, TG and higher FPI concentration, whereas there were no significant differences in TC, HDL-C and LDL-C. It was concluded that TJQ exercise could be used as an intervention tool to improve glycaemic control and serum TG level in the elderly people. Future research with TJQ of different styles and exercise of different intensities were recommended.
Symptom Combinations Assessed in Traditional Chinese Medicine and Its Predictive Role in ACR20 Efficacy Response in Rheumatoid Arthritis
Authors: He Yiting , Lu Aiping , Lu Cheng , Zha Yinglin , Yan Xiaoping , Song Yuejin , Zeng Shengping , Liu Wei , Zhu Wanhua , Su Li , Feng Xinghua , Qian Xian , Tsang Ian
Published: August 2008

The predictive roles of symptom combination traditionally evaluated in traditional Chinese medicine (TCM) in the treatment of rheumatoid arthritis (RA) were explored. Three hundred and ninety six patients were randomly divided into 197 subjects receiving Western medicine therapy (WM) and 199 subjects receiving TCM therapy (TCM). A complete physical examination and 18 clinical manifestations typically assessed in TCM were recorded before the randomization. The ACR responses were used for efficacy evaluation. ACR20 and 50 responses with WM treatment were higher than in the TCM group. The 18 symptoms in RA could be clustered into 4 symptom combinations with factor analysis, which represent joint symptoms, cold pattern, deficiency pattern and hot pattern in TCM respectively. TCM would be more effective in patients with weak-symptom combination 3 (deficiency pattern in TCM), and WM would be more effective in patients with symptom combination 2 (cold pattern in TCM). Symptom combinations judged with TCM may have influence on the efficacy of therapy in the treatment of RA.
The Protective Effect of Yi-Qi-Yang-Yin-Ye, a Compound of Traditional Chinese Herbal Medicine in Diet-Induced Obese Rats
Authors: He Guang-Wei , Qu Wei-Jing , Fan Bin , Jing Rong , He Rong
Published: August 2008

The present study was undertaken to determine the effect of Yi-Qi-Yang-Yin-Ye (Y-Q-Y-Y-Y), a compound of Traditional Chinese Herbal Medicine, on insulin resistance (IR) in the diet-induced obese rat model induced by intravenous injection with a low dose of streptozotocin and fed a high fat and high caloric diet. Y-Q-Y-Y-Y (2, 4, 8 g/kg) was administered via gavage daily for 4 weeks. The results showed that Y-Q-Y-Y-Y treatment decreased the levels of body weight, total cholesterol (TC), triglycerides (TG), low density lipoprotein-cholesterol (LDL-C), free fatty acid (FFA), insulin (INS) and fast blood glucose (FBG) and increased the level of high density lipoprotein-cholesterol (HDL-C) in the diet-induced obese rats. Glucose tolerance was improved in the diet-induced obese rats treated with Y-Q-Y-Y-Y as well as GIR (glucose infusion rate) in the hyperinsulinemic euglycemic clamp experiment compared to the model control rats (p < 0.01). Moreover, treatment with Y-Q-Y-Y-Y up-regulated glycogen contents in both liver and skeletal muscle and increased insulin receptor amounts on the erythrocytes surface as assessed by using 125I-labeled auto-antibodies against insulin receptors. Taken together, our data suggested that Yi-Qi-Yang-Yin-Ye ameliorates insulin resistance in the diet-induced obese rats.
Active Compounds Isolated from Traditional Chinese Prescription Wen-Pi-Tang Protecting Against Peroxynitrite-Induced LLC-PK1 Cell Damage
Authors: Rhyu Dong Young , Kang Ki Sung , Sekiya Michiko , Tanaka Takashi , Park Jong Cheol , Yokozawa Takako
Published: August 2008

Wen-Pi-Tang, a traditional Chinese prescription, has been widely used for the treatment of patients with moderate chronic renal failure in China. Although the protective effect of Wen-Pi-Tang on peroxynitrite (ONOO-)-induced renal tubular epithelial LLC-PK1 cell damage was elucidated in our previous research, the active components of Wen-Pi-Tang have not yet been fully clarified. Therefore in the present study, we investigated the active components by using a cellular ONOO-generation system. As a result, p-coumaric acid, 4-(4'-hydroxylphenyl)-2-butanone 4'-O-glucopyranoside, gallic acid 3-O-(6'-O-galloyl)-β-d-glucopyranoside, procyanidin B-1, procyanidin B-3, and (+)-catechin were isolated as active compounds inhibiting cellular ONOO- formation and cytotoxicity. In particular, the content of (+)-catechin was significantly higher than those of the other compounds, and the (+)-catechin structure was located in procyanidins B-1 and B-3. Therefore, the major bioactivity of Wen-Pi-Tang against ONOO--induced cytotoxicity in LLC-PK1 cells was thought to be mediated by (+)-catechin. Although we cannot disregard the synergetic effect of various components in Wen-Pi-Tang, (+)-catechin is a major active compound protecting against ONOO--induced LLC-PK1 cell damage and may be used as an index to qualify the ONOO--inhibitory activity of Wen-Pi-Tang extract.
Functional Analysis of Cultured Neural Cells for Evaluating Cold/Cool- and Hot/Warm-Natured Chinese Herbs
Authors: Liu Yan-Qiu , Cheng Meng-Chun , Wang Long-Xing , Zhao Nan , Xiao Hong-Bin , Wang Zheng-Tao
Published: August 2008

Recently, modern scientific research has been required to understand pharmacological basis of traditional Chinese medicine (TCM) theory based on the ancient clinical experience, and to investigate the molecular mechanisms of action of Chinese herbs. Here, 20 Chinese herbs, classified into 4 properties (hot, warm, cold and cool) of TCM, were analyzed for their ability to exhibit antioxidant action, to enhance glucose uptake by murine microglia N9 cells, and to influence neurotransmitter norepinephrine (NE) release from rat pheochromocytoma PC12 cells. We found a generally protective effect of both hot/warm-natured and cold/cool-natured herbs against H 2 O 2-induced N9 cell death, partially by elevating superoxide dismutase (SOD) activity. Glucose uptake was elevated after treatment with some hot/warm-natured herbs. In addition, most herbs with hot/warm nature tended to stimulate NE release, while such stimulatory effect was not observed in the herbs with cold/cool nature. Two cold/cool-natured herbs, Rhizoma coptidis and Radix scutellariae, even significantly suppressed the release. These results suggest that the distinct abilities of Chinese herbs to regulate neural cell functions appear to be correlated with their natures identified in traditional TCM theory, and may be a useful guide for their utility in neural degenerative diseases.
Relationship Between San-Huang-Xie-Xin-Tang and Its Herbal Components on the Gene Expression Profiles in HepG2 Cells
Authors: Cheng Wen-Yu , Wu Shih-Lu , Hsiang Chien-Yun , Li Chia-Cheng , Lai Tung-Yuan , Lo Hsin-Yi , Shen Wei-Shuen , Lee Chang-Hsien , Chen Jaw-Chyun , Wu Hsiu-Ching , Ho Tin-Yun
Published: August 2008

Traditional Chinese medicine (TCM) has been used for thousands of years. Most Chinese herbal formulae consist of several herbal components and have been used to treat various diseases. However, the mechanisms of most formulae and the relationship between formulae and their components remain to be elucidated. Here we analyzed the putative mechanism of San-Huang-Xie-Xin-Tang (SHXXT) and defined the relationship between SHXXT and its herbal components by microarray technique. HepG2 cells were treated with SHXXT or its components and the gene expression profiles were analyzed by DNA microarray. Gene set enrichment analysis indicated that SHXXT and its components displayed a unique anti-proliferation pattern via p53 signaling, p53 activated, and DNA damage signaling pathways in HepG2 cells. Network analysis showed that most genes were regulated by one molecule, p53. In addition, hierarchical clustering analysis showed that Rhizoma Coptis shared a similar gene expression profile with SHXXT. These findings may explain why Rhizoma Coptis is the principle herb that exerts the major effect in the herbal formula, SHXXT. Moreover, this is the first report to reveal the relationship between formulae and their herbal components in TCM by microarray and bioinformatics tools.
CONSTRAINTS TO DECELERATION PARAMETERS BY RECENT COSMIC OBSERVATIONS
Authors: XU LIXIN , LIU HONGYA
Published: August 2008

In this paper, two simple parametrized deceleration parameters [Formula: see text] and [Formula: see text] areconstrained by using the latest SNe Ia Gold dataset, observational Hubble data and their combination. It is found that the transition redshift from decelerated expansion to accelerated expansion zT and current decelerated parameter values q0 are consistent with each other in 1σ region by only using SNe Ia Gold dataset and observational Hubble data in three parametrizations respectively. By combining the SNe Ia Gold dataset and observational Hubble data together, a tight constraint is obtained. With this combined constraint, zT is [Formula: see text] and [Formula: see text] with 1σ error in the parametrizations respectively.
ACTIVE TRACKING CONTROL OF THE HYPERCHAOTIC LORENZ SYSTEM
Authors: WANG XINGYUAN , NIU DAHAI , WANG MINGJUN
Published: August 2008

A nonlinear active tracking controller for the four-dimensional hyperchaotic Lorenz system is designed in the paper. The controller enables this hyperchaotic system to track all kinds of reference signals, such as the sinusoidal signal. The self-synchronization of the hyperchaotic Lorenz system and the different-structure synchronization with other chaotic systems can also be realized. Numerical simulation results show the effectiveness of the controller.
COMPUTING THE HAUSDORFF DISTANCE BETWEEN CURVED OBJECTS
Authors: ALT HELMUT , SCHARF LUDMILA
Published: August 2008

The Hausdorff distance between two sets of curves is a measure for the similarity of these objects and therefore an interesting feature in shape recognition. If the curves are algebraic computing the Hausdorff distance involves computing the intersection points of the Voronoi edges of the one set with the curves in the other. Since computing the Voronoi diagram of curves is quite difficult we characterize those points algebraically and compute them using the computer algebra system SYNAPS. This paper describes in detail which points have to be considered, by what algebraic equations they are characterized, and how they actually are computed.
A PROOF OF THE HORTON LAW OF STREAM NUMBERS FOR THE TOKUNAGA MODEL OF RIVER NETWORKS
Authors: MCCONNELL MEGAN , GUPTA VIJAY K.
Published: August 2008

The Horton laws of stream numbers and magnitudes are proved in the limit of large network order for the broad class of Tokunaga model of river networks. Tokunaga model is built on the assumption of mean self-similarity in the side tributary structure, and an additional assumption of Tokunaga self-similarity, which is supported by data from real networks. Tokunaga model is gaining increasing recognition in the recent literature, because data supports several predictions of the model.
VIBRATION SPECTRA OF FINITELY RAMIFIED, SYMMETRIC FRACTALS
Authors: BAJORIN N. , CHEN T. , DAGAN A. , EMMONS C. , HUSSEIN M. , KHALIL M. , MODY P. , STEINHURST B. , TEPLYAEV A.
Published: August 2008

We show how to calculate the spectrum of the Laplacian operator on fully symmetric, finitely ramified fractals. We consider well-known examples, such as the unit interval and the Sierpiński gasket, and much more complicated ones, such as the hexagasket and a non-post critically finite self-similar fractal. We emphasize the low computational demands of our method. As a conclusion, we give exact formulas for the limiting distribution of eigenvalues (the integrated density of states), which is a purely atomic measure (except in the classical case of the interval), with atoms accumulating to the Julia set of a rational function. This paper is the continuation of the work published by the same authors in Ref. 1.
Karst geohazards in the UK: the use of digital data for hazard management
Authors: Farrant A.R. , Cooper A.H.
Published: August 2008

An essential prerequisite for any engineering or hydrogeological investigation of soluble rocks is the identification and description of their characteristic, observable and detectable dissolution features, such as stream sinks, springs, sinkholes and caves. The British Geological Survey (BGS) is creating a National Karst Database (NKD) that records such features across the country. The database currently covers much of the region underlain by Carboniferous Limestone, the Chalk, and particularly the Permo-Triassic gypsum and halite where rapid, active dissolution has caused significant subsidence and building damage. In addition to, and separate from, the identification of specific karst features, the BGS has created a National Karst Geohazard geographical information system (GIS). This has been created to identify areas that may potentially contain karst geohazards. Initially, all the soluble rock units identified from the BGS 1:50 000 scale digital geological map are extracted. Each soluble unit has been given an objective score, interpreted, as based on factors including lithology, topography, geomorphological position and characteristic superficial cover deposits. This national zonation of these soluble rocks can then be used to identify areas where the occurrence potential for karstic features is significant, and where dissolution features might affect the stability of buildings and infrastructure, or where karstic groundwater flow might occur. Both datasets are seen as invaluable scientific tools that have already been widely used to support site investigation, groundwater investigations, planning, construction and the insurance underwriting businesses.
Planning for development on land that is potentially prone to subsidence in England
Authors: Brook D. , Marker B.
Published: August 2008

Subsidence problems that may constrain, add to the costs of, or delay development are widespread in England. Extensive sources of information are available, such as datasets held by the British Geological Survey and the Coal Authority, but are not always used fully in planning for development and determining planning applications. Planning Policy Guidance (PPG) Note 14 on instability was published in 1990 and later augmented by a specific Annex 2 on subsidence and planning. That guidance improved the consideration given to subsidence in planning but key advances tended to be focused on specific areas selected by Government for demonstration projects and a major derelict land reclamation initiative. Elsewhere, implementation has been patchy. Although subsidence issues tended to be taken into account in areas of extensive past underground mining, appreciation of the issues has been more difficult to establish where potential subsidence relates to isolated mining or natural underground cavities. Recent reform of the planning system has led to continuing replacement of PPGs by a new series of Planning Policy Statements (PPSs). There are currently no plans to bring PPG14 or its annexes into a PPS format and, therefore, a risk that it will gradually be forgotten and that good planning responses to subsidence may decline. Sustainability appraisal of spatial plans and environmental impact assessments of development proposals could help to ensure that this important issue is not overlooked, but existing guidance on assessments does not refer explicitly to subsidence.
The impacts of coal mining subsidence on groundwater resources management of the East Midlands Permo-Triassic Sandstone aquifer, England
Authors: Shepley M.G. , Pearson A.D. , Smith G.D. , Banton C.J.
Published: August 2008

There are extensive concealed coal mines beneath the East Midlands Permo-Triassic Sandstone aquifer, most of which have used longwall mining techniques. Knowledge of the pumping regimes of the concealed mines shows that there is currently little vertical leakage from the Permo-Triassic Sandstone into these mines. Long-term plans to control the groundwater rebound should prevent any large-scale pollution of the Permo-Triassic Sandstone aquifer system from ingress of mine waters. Currently, the largest impacts on the Permo-Triassic Sandstone aquifer system stem from subsidence associated with the mine workings. This paper examines the impacts on groundwater–surface water interaction, in the context of improving the surface water environment to mitigate effects of long-term over-abstraction. Integral to the assessment of the groundwater–surface water interactions are (i) the change to the hydraulic characteristics of the aquifer system related to the fracturing in the Permo-Triassic Sandstone that the subsidence induces and (ii) the reliability of the installations used to monitor groundwater levels and flows across the aquifer system. These two temporal impacts can be difficult to assess from the available data. The former tends to increase aquifer transmissivity, whereas the latter leads to the underestimation of the impacts of groundwater abstraction caused by datum subsidence of several metres. Two example case histories of impacts on groundwater–surface water interactions are considered: streambed fissuring in the catchments of the River Maun and River Meden, and flow improvements caused by subsidence in the Dover Beck catchment. These two case histories show that there are both beneficial and detrimental outcomes for groundwater resources management caused by coal mining induced subsidence.
Forecast of a collapse location: new approach
Authors: Khomenko V.P.
Published: August 2008

One of the central problems of a collapse hazard evaluation is the answer to the question: at what point on a collapse-prone site will a future collapse sink be located? If we have information about underground cavities, which can be the reason for a collapse, this problem may be solved fairly easily; otherwise, prediction is more difficult. This paper describes an approach to define the most probable location of a collapse at the stage of preparation for this event. The situation when we assume the presence of underground cavities, but have no exact information about them, is considered. This is typical for karst regions or for piping events. The approach includes the mathematical analysis of data from cone penetration tests or dynamic probing tests, carried out during standard site investigation. The basic principle is the recognized correspondence between the spatial distribution of these test data and the stress distribution in soils above an underground cavity. The results of practical application of this approach are given for some examples in Russia. In particular, in the city of Dzerzhinsk (near Nizhniy Novgorod) the forecast was completely confirmed, when inside a hazardous zone delineated in 1994 a collapse sink of karst origin was formed in 1996.
Regulation of maternal ACTH in ovine pregnancy: does progesterone play a role?
Authors: Keller-Wood Maureen , Wood Charles E.
Published: August 2008

Pregnancy is characterized by increased plasma adrenocorticotropic hormone (ACTH) and cortisol. Studies suggest that progesterone acts as an antagonist at mineralocorticoid receptors. Therefore, we tested the hypothesis that chronic progesterone, produced by treatment of nonpregnant ewes or during pregnancy, will result in increased plasma ACTH relative to the plasma cortisol concentrations. We studied three groups of ewes: ovariectomized nonpregnant, nonpregnant treated with progesterone, and pregnant ewes. In two series of studies, ewes were adrenalectomized and replaced with 0.35 mg·kg−1·day−1or 0.5 mg·kg−1·day−1cortisol. In both studies, aldosterone was infused at 3 μg·kg−1·day−1. In the first study, additional infusions of cortisol over 24 h were used to increase daily replacement doses to 0.5, 1, or 1.5 mg·kg−1·day−1, and intact pregnant and nonpregnant ewes were studied with infusions of cortisol at 0, 0.5, and 1 mg·kg−1·day−1. In adrenalectomized ewes chronically replaced to 0.35 mg·kg−1·day−1cortisol, plasma ACTH concentrations were decreased significantly in the nonpregnant progesterone-treated ewes compared with the ovariectomized nonpregnant ewes. With 0.5 mg·kg−1·day−1cortisol, plasma ACTH levels were greater in pregnant ewes than in nonpregnant ewes with or without progesterone. Overall plasma ACTH levels at 0.35 mg·kg−1·day−1were significantly related to the plasma protein concentration, suggesting that the ACTH levels in the hypocorticoid ewes are most closely related to plasma volume. Across all steroid doses, ACTH was positively related to plasma proteins and progesterone, and negatively related to cortisol. We conclude that increased progesterone does not alter the feedback relation of cortisol to ACTH, but may modulate ACTH indirectly through plasma volume.
Termination Zones of Functionally Characterized Spinothalamic Tract Neurons Within the Primate Posterior Thalamus
Authors: Davidson Steve , Zhang Xijing , Khasabov Sergey G. , Simone Donald A. , Giesler Glenn J.
Published: August 2008

The primate posterior thalamus has been proposed to contribute to pain sensation, but its precise role is unclear. This is in part because spinothalamic tract (STT) neurons that project to the posterior thalamus have received little attention. In this study, antidromic mapping was used to identify individual STT neurons with axons that projected specifically to the posterior thalamus in Macaca fascicularis. Each axon was located by antidromic activation at low stimulus amplitudes (<30 μA) and was then surrounded distally by a grid of stimulating points in which 500-μA stimuli were unable to activate the axon antidromically, thereby indicating the termination zone. Several nuclei within the posterior thalamus were targets of STT neurons: the posterior nucleus, suprageniculate nucleus, magnocellular part of the medial geniculate nucleus, and limitans nucleus. STT neurons projecting to the ventral posterior inferior nucleus were also studied. Twenty-five posterior thalamus-projecting STT neurons recorded in lumbar spinal cord were characterized by their responses to mechanical, thermal, and chemical stimuli. Sixteen of 25 neurons were recorded in the marginal zone and the balance was located within the deep dorsal horn. Thirteen neurons were classified as wide dynamic range and 12 as high threshold. One-third of STT neurons projecting to posterior thalamus responded to noxious heat (50°C). Two-thirds of those tested responded to cooling. Seventy-one percent responded to an intradermal injection of capsaicin. These data indicate that the primate STT transmits noxious and innocuous mechanical, thermal, and chemical information to multiple posterior thalamic nuclei.
Surveillance for the Management of Small Renal Masses
Authors: Ozsoy Mehmet , Klatte Tobias , Waldert Matthias , Remzi Mesut
Published: August 2008

Surveillance is a new management option for small renal masses (SRMs) in aged and infirm patients with short-life expectancy. The current literature on surveillance of SRM contains mostly small, retrospective studies with limited data. Imaging alone is inadequate for suggesting the aggressive potential of SRM for both diagnosis and followup. Current data suggest that a computed tomography (CT) or magnetic resonance imaging (MRI) every 3 months in the 1st year, every 6 months in the next 2 years, and every year thereafter, is appropriate for observation. The authors rather believe in active surveillance with mandatory initial and followup renal tumor biopsies than classical observation. Since not all SRMs are harmless, selection criteria for active surveillance need to be improved. In addition, there is need for larger studies in order to better outline oncological outcome and followup protocols.
Some Sufficient Conditions for Analytic Functions to Belong to 𝒬K,0(p, q) Space
Authors: Meng Xiaoge
Published: August 2008

This paper gives some sufficient conditions for an analytic function to belong to the space consisting of all analytic functions
f on the unit disk such
IR‐Improved DGLAP‐CS Theory
Authors: Ward B. F. L.
Published: August 2008

We show that it is possible to improve the infrared aspects of the standard treatment
of the DGLAP‐CS evolution theory to take into account a large class of higher‐order
corrections that significantly improve the precision of the theory for any given level of fixed‐order calculation of its respective kernels. We illustrate the size of the effects we resum using the moments of the parton distributions.
Enhanced Radar Imaging in Uncertain Environment: A Descriptive Experiment Design Regularization Approach
Authors: Shkvarko Yuriy , Perez-Meana Hector , Castillo-Atoche Alejandro
Published: August 2008

A new robust technique for high‐resolution reconstructive imaging is developed as required for enhanced remote sensing (RS) with imaging array radar or/and synthetic aperture radar (SAR) operating in an uncertain RS environment. The operational scenario uncertainties are associated with the unknown statistics of perturbations of the signal formation operator (SFO) in turbulent medium, imperfect array calibration, finite dimensionality of measurements, uncontrolled antenna vibrations, and random carrier trajectory deviations in the case of SAR. We propose new descriptive experiment design regularization (DEDR) approach to treat the uncertain radar image enhancement/reconstruction problems. The proposed DEDR incorporates into the minimum risk (MR) nonparametric estimation strategy the experiment design‐motivated operational constraints algorithmically coupled with the worst‐case statistical performance (WCSP) optimization‐based regularization. The MR objective functional is constrained by the WCSP information, and the robust DEDR image reconstruction operator applicable to the scenarios with the low‐rank uncertain estimated data correlation matrices is found. We report and discuss some simulation results related to enhancement of the uncertain SAR imagery indicative of the significantly increased performance efficiency gained with the developed approach.
p70 S6 Kinase Promotes Epithelial to Mesenchymal Transition through Snail Induction in Ovarian Cancer Cells
Authors: Pon Yuen L. , Zhou Hong Y. , Cheung Annie N.Y. , Ngan Hextan Y.S. , Wong Alice S.T.
Published: August 2008

p70 S6 kinase (p70S6K) is a downstream effector of phosphatidylinositol 3-kinase and is frequently activated in human ovarian cancer. Here we show that p70S6K functions in epithelial to mesenchymal transition (EMT) responsible for the acquisition of invasiveness during tumor progression. This tumorigenic activity is associated with the ability of p70S6K to repress E-cadherin through the up-regulation of Snail. p70S6K activation induced phenotypic changes consistent with EMT in ovarian cancer cells: The cells lost epithelial cell morphology, acquired fibroblast-like properties, and showed reduced intercellular adhesion. Western blot showed that p70S6K activation led to decreased expression of the epithelial marker E-cadherin and increased expression of mesenchymal markers N-cadherin and vimentin. Inhibition of p70S6K by a specific inhibitor or small interfering RNA reversed the shift of EMT markers. Importantly, p70S6K activation also stimulated the expression of Snail, a repressor of E-cadherin and an inducer of EMT, but not other family members such as Slug. This induction of Snail was regulated at multiple levels by increasing transcription, inhibiting protein degradation, and enhancing nuclear localization of Snail. RNA interference–mediated knockdown of Snail suppressed p70S6K-induced EMT, confirming that the effect was Snail specific. Furthermore, phospho (active)-p70S6K staining correlated with higher tumor grade. We also showed a significant positive correlation between p70S6K activation and Snail expression in ovarian cancer tissues. These results indicate that p70S6K may play a critical role in tumor progression in ovarian cancer through the induction of EMT. Targeting p70S6K may thus be a useful strategy to impede cancer cell invasion and metastasis. [Cancer Res 2008;68(16):6524–32]
Re-Expression of Transcription FactorATF5in Hepatocellular Carcinoma Induces G2-M Arrest
Authors: Gho Jennifer W-M. , Ip Wai-Ki , Chan Kathy Y-Y. , Law Priscilla T-Y. , Lai Paul B-S. , Wong Nathalie
Published: August 2008

Transcription factors represent an important class of genes that play key roles in controlling cellular proliferation, cell cycle modulation, and attractive targets for cancer therapy. Here, we report on the novel finding of common ATF5 down-regulations in hepatocellular carcinoma (HCC), a highly malignant tumor with a dismal clinical course. Array-based mapping in HCC highlighted a high and consistent incidence of transcription factor ATF5 repressions on regional chr.19q13. By quantitative reverse transcription-PCR, profound down-regulations of ATF5 were further suggested in 78% of HCC tumors (60 of 77 cases) compared to their adjacent nontumoral liver (P = 0.0004). Restoration of ATF5 expression in 3 nonexpressing HCC cell lines demonstrated a consistent growth inhibitory effect (P < 0.029) but minimal induction on cellular apoptosis. Subsequent flow cytometric investigations revealed a G2-M cell cycle arrest in HCC cells that were ectopically transfected with ATF5 (P < 0.002). The differential expressed genes from the functional effects of ATF5 were examined by array profiling. Over a hundred genes were identified, among which ID1 contains the ATF/CREB target binding sequences within its promoter region. An inverse relationship between ATF5 expressions with ID1 transcriptions was verified in HCC (P = 0.019), and a direct interaction of ATF5 on the promoter of ID1 was further demonstrated from electromobility shift assay. Examination of causal events underlying the silencing of ATF5 in HCC suggested copy number losses, promoter hypermethylation, histone deacetylation, and DNA mutations to be the likely inactivating mechanisms. In conclusion, our finding supports a tumor suppressive role for ATF5 in HCC, and highlighted ID1 as a potential downstream target. [Cancer Res 2008;68(16):6743–51]
CHR-2797: An Antiproliferative Aminopeptidase Inhibitor that Leads to Amino Acid Deprivation in Human Leukemic Cells
Authors: Krige David , Needham Lindsey A. , Bawden Lindsay J. , Flores Nicolas , Farmer Hannah , Miles Lauren E.C. , Stone Erica , Callaghan Juliana , Chandler Stephen , Clark Vanessa L. , Kirwin-Jones Patricia , Legris Valérie , Owen Jo , Patel Thakor , Wood Steve , Box Gary , Laber David , Odedra Rajesh , Wright Annette , Wood L. Michael , Eccles Suzanne A. , Bone Elisabeth A. , Ayscough Andrew , Drummond Alan H.
Published: August 2008

CHR-2797 is a novel metalloenzyme inhibitor that is converted into a pharmacologically active acid product (CHR-79888) inside cells. CHR-79888 is a potent inhibitor of a number of intracellular aminopeptidases, including leucine aminopeptidase. CHR-2797 exerts antiproliferative effects against a range of tumor cell lines in vitro and in vivo and shows selectivity for transformed over nontransformed cells. Its antiproliferative effects are at least 300 times more potent than the prototypical aminopeptidase inhibitor, bestatin. However, the mechanism by which inhibition of these enzymes leads to proliferative changes is not understood. Gene expression microarrays were used to profile changes in mRNA expression levels in the human promyelocytic leukemia cell line HL-60 treated with CHR-2797. This analysis showed that CHR-2797 treatment induced a transcriptional response indicative of amino acid depletion, the amino acid deprivation response, which involves up-regulation of amino acid synthetic genes, transporters, and tRNA synthetases. These changes were confirmed in other leukemic cell lines sensitive to the antiproliferative effects of CHR-2797. Furthermore, CHR-2797 treatment inhibited phosphorylation of mTOR substrates and reduced protein synthesis in HL-60 cells, both also indicative of amino acid depletion. Treatment with CHR-2797 led to an increase in the concentration of intracellular small peptides, the substrates of aminopeptidases. It is suggested that aminopeptidase inhibitors, such as CHR-2797 and bestatin, deplete sensitive tumor cells of amino acids by blocking protein recycling, and this generates an antiproliferative effect. CHR-2797 is orally bioavailable and currently undergoing phase II clinical investigation in the treatment of myeloid leukemia. [Cancer Res 2008;68(16):6669–79]
Leptin Enhances Cholangiocarcinoma Cell Growth
Authors: Fava Giammarco , Alpini Gianfranco , Rychlicki Chiara , Saccomanno Stefania , DeMorrow Sharon , Trozzi Luciano , Candelaresi Cinzia , Venter Julie , Di Sario Antonio , Marzioni Marco , Bearzi Italo , Glaser Shannon , Alvaro Domenico , Marucci Luca , Francis Heather , Svegliati-Baroni Gianluca , Benedetti Antonio
Published: August 2008

Cholangiocarcinoma is a strongly aggressive malignancy with a very poor prognosis. Effective therapeutic strategies are lacking because molecular mechanisms regulating cholangiocarcinoma cell growth are unknown. Furthermore, experimental in vivo animal models useful to study the pathophysiologic mechanisms of malignant cholangiocytes are lacking. Leptin, the hormone regulating caloric homeostasis, which is increased in obese patients, stimulates the growth of several cancers, such as hepatocellular carcinoma. The aim of this study was to define if leptin stimulates cholangiocarcinoma growth. We determined the expression of leptin receptors in normal and malignant human cholangiocytes. Effects on intrahepatic cholangiocarcinoma (HuH-28) cell proliferation, migration, and apoptosis of the in vitro exposure to leptin, together with the intracellular pathways, were then studied. Moreover, cholangiocarcinoma was experimentally induced in obese fa/fa Zucker rats, a genetically established animal species with faulty leptin receptors, and in their littermates by chronic feeding with thioacetamide, a potent carcinogen. After 24 weeks, the effect of leptin on cholangiocarcinoma development and growth was assessed. Normal and malignant human cholangiocytes express leptin receptors. Leptin increased the proliferation and the metastatic potential of cholangiocarcinoma cells in vitro through a signal transducers and activators of transcription 3–dependent activation of extracellular signal-regulated kinase 1/2. Leptin increased the growth and migration, and was antiapoptotic for cholangiocarcinoma cells. Moreover, the loss of leptin function reduced the development and the growth of cholangiocarcinoma. The experimental carcinogenesis model induced by thioacetamide administration is a valid and reproducible method to study cholangiocarcinoma pathobiology. Modulation of the leptin-mediated signal could be considered a valid tool for the prevention and treatment of cholangiocarcinoma. [Cancer Res 2008;68(16):6752–61]
Identification of a Novel Recepteur d'Origine Nantais/c-Met Small-Molecule Kinase Inhibitor with Antitumor Activity In vivo
Authors: Zhang Yihong , Kaplan-Lefko Paula J. , Rex Karen , Yang Yajing , Moriguchi Jodi , Osgood Tao , Mattson Bethany , Coxon Angela , Reese Monica , Kim Tae-Seong , Lin Jasmine , Chen April , Burgess Teresa L. , Dussault Isabelle
Published: August 2008

Recepteur d'origine nantais (RON) is a receptor tyrosine kinase closely related to c-Met. Both receptors are involved in cell proliferation, migration, and invasion, and there is evidence that both are deregulated in cancer. Receptor overexpression has been most frequently described, but other mechanisms can lead to the oncogenic activation of RON and c-Met. They include activating mutations or gene amplification for c-Met and constitutively active splicing variants for RON. We identified a novel inhibitor of RON and c-Met, compound I, and characterized its in vitro and in vivo activities. Compound I selectively and potently inhibited the kinase activity of RON and c-Met with IC50s of 9 and 4 nmol/L, respectively. Compound I inhibited hepatocyte growth factor–mediated and macrophage-stimulating protein–mediated signaling and cell migration in a dose-dependent manner. Compound I was tested in vivo in xenograft models that either were dependent on c-Met or expressed a constitutively active form of RON (RONΔ160 in HT-29). Compound I caused complete tumor growth inhibition in NIH3T3 TPR-Met and U-87 MG xenografts but showed only partial inhibition in HT-29 xenografts. The effect of compound I in HT-29 xenografts is consistent with the expression of the activating b-Raf V600E mutation, which activates the mitogen-activated protein kinase pathway downstream of RON. Importantly, tumor growth inhibition correlated with the inhibition of c-Met–dependent and RON-dependent signaling in tumors. Taken together, our results suggest that a small-molecule dual inhibitor of RON/c-Met has the potential to inhibit tumor growth and could therefore be useful for the treatment of patients with cancers where RON and/or c-Met are activated. [Cancer Res 2008;68(16):6680–7]
The Nuclear Factor-κB Pathway Controls the Progression of Prostate Cancer to Androgen-Independent Growth
Authors: Jin Ren Jie , Lho Yongsoo , Connelly Linda , Wang Yongqing , Yu Xiuping , Saint Jean Leshana , Case Thomas C. , Ellwood-Yen Katharine , Sawyers Charles L. , Bhowmick Neil A. , Blackwell Timothy S. , Yull Fiona E. , Matusik Robert J.
Published: August 2008

Typically, the initial response of a prostate cancer patient to androgen ablation therapy is regression of the disease. However, the tumor will progress to an “androgen-independent” stage that results in renewed growth and spread of the cancer. Both nuclear factor-κB (NF-κB) expression and neuroendocrine differentiation predict poor prognosis, but their precise contribution to prostate cancer progression is unknown. This report shows that secretory proteins from neuroendocrine cells will activate the NF-κB pathway in LNCaP cells, resulting in increased levels of active androgen receptor (AR). By blocking NF-κB signaling in vitro, AR activation is inhibited. In addition, the continuous activation of NF-κB signaling in vivo by the absence of the IκBα inhibitor prevents regression of the prostate after castration by sustaining high levels of nuclear AR and maintaining differentiated function and continued proliferation of the epithelium. Furthermore, the NF-κB pathway was activated in the ARR2PB-myc-PAI (Hi-myc) mouse prostate by cross-breeding into a IκBα+/− haploid insufficient line. After castration, the mouse prostate cancer continued to proliferate. These results indicate that activation of NF-κB is sufficient to maintain androgen-independent growth of prostate and prostate cancer by regulating AR action. Thus, the NF-κB pathway may be a potential target for therapy against androgen-independent prostate cancer. [Cancer Res 2008;68(16):6762–9]
Up-regulation of Mcl-1 Is Critical for Survival of Human Melanoma Cells upon Endoplasmic Reticulum Stress
Authors: Jiang Chen Chen , Lucas Keryn , Avery-Kiejda Kelly A. , Wade Margaret , deBock Charles E. , Thorne Rick F. , Allen John , Hersey Peter , Zhang Xu Dong
Published: August 2008

We have previously shown that most melanoma cell lines are insensitive to endoplasmic reticulum (ER) stress–induced apoptosis, and this involves activation of the mitogen-activated protein/extracellular signal-regulated kinase (MEK)/ERK signaling pathway and expression of the apoptosis repressor with caspase recruitment domain (ARC) protein in the cells. In the present study, we show that up-regulation of the antiapoptotic Bcl-2 family member Mcl-1 is another mechanism critical for protection of melanoma cells against ER stress–induced apoptosis. Inhibition of Mcl-1 by small interference RNA (siRNA) rendered melanoma cells sensitive to apoptosis induced by the ER stress inducers thapsigargin and tunicamycin, but this sensitization was partially reversed by siRNA knockdown of PUMA or Noxa, as shown in Mcl-1–deficient melanoma cells. Both PUMA and Noxa were increased by ER stress through transcriptional up-regulation, but only up-regulation of Noxa was dependent on p53, whereas up-regulation of PUMA seemed to be mediated by a p53-independent mechanism(s). Up-regulation of Mcl-1 was also due to increased transcription that involved the IRE1α and activating transcription factor 6 signaling pathways of the unfolded protein response. In addition, activation of the MEK/ERK signaling pathway seemed to be necessary for optimal up-regulation of Mcl-1. Taken together, these results reveal the mechanisms of resistance of melanoma cells to apoptosis induction mediated by BH3-only proteins upon ER stress, and identify Mcl-1 as a target for the treatment of melanoma in combination with therapeutics that induce ER stress. [Cancer Res 2008;68(16):6708–17]
A Novel Diterpene Suppresses CWR22Rv1 Tumor Growth In vivo through Antiproliferation and Proapoptosis
Authors: Lin Feng-Min , Tsai Chin-Hsien , Yang Yu-Chih , Tu Wei-Chun , Chen Li-Ru , Liang Yun-Sa , Wang Sheng-Yang , Shyur Lie-Fen , Chien Shih-Chang , Cha Tai-Lung , Hsiao Pei-Wen
Published: August 2008

Androgen receptor (AR) is the main therapeutic target for treatment of metastatic prostate cancers (PCa). As recurrent tumors restore AR activity independent of hormones, new therapies that abolish AR activity have been sought to prevent or delay the emergence of ablation-resistant disease. Here, we report that a novel abietane diterpene, 6-hydroxy-5,6-dehydrosugiol (HDHS), isolated from the stem bark of Cryptomeria japonica, was a potent AR antagonist in PCa cells. HDHS treatment of androgen-dependent LNCaP and androgen-responsive 22Rv1 cells induced apoptosis as shown by nucleosome release, activation of caspase-3 and caspase-7, and cleavage of poly(ADP-ribose) polymerase accompanied with concomitant up-regulation of tumor suppressor p53. HDHS also decreased the protein expression of cyclins (D1 and E), cyclin-dependent kinases (CDK2, CDK4, and CDK6), and retinoblastoma phosphorylation in PCa cells, which suggest cell cycle arrest in the G1 phase. Oral administration of HDHS at 0.5 and 2.5 mg/kg once daily for 24 days to 22Rv1 PCa xenografted mice suppressed tumor growth by 22% and 39%, respectively, in association with decreased proliferation and increased apoptosis in tumor cells, which further correlated with increased levels of HDHS in plasma and tumors. Overall, our data suggest that HDHS has potential for use in chemoprevention and chemotherapy of PCa. [Cancer Res 2008;68(16):6634–42]