bluuebunny/crossref_metadata_2025_split huggingface dataset:
Use of laser speckle flowgraphy in ocular blood flow research
Authors: Sugiyama Tetsuya , Araie Makoto , Riva Charles E. , Schmetterer Leopold , Orgul Selim 
Published: September 2009

Acta Ophthalmol. 2010: 88: 723–729Abstract.Laser speckle flowgraphy (LSFG) allows for the quantitative estimation of blood flow in the optic nerve head, choroid, retina and iris in vivo. It was developed to facilitate the non‐contact analysis of ocular blood flow in living eyes, utilizing the laser speckle phenomenon. The technique uses a fundus camera, a diode laser, an image sensor, an infrared charge‐coupled device (CCD) camera and a high‐resolution digital CCD camera. Normalized blur (NB), an approximate reciprocal of speckle contrast, represents an index of blood velocity, and shows a good correlation with tissue blood flow rates determined with the microsphere method in the retina, choroid or iris, as well as blood flow rates determined with the hydrogen gas clearance method in the optic nerve head. The square blur ratio (SBR), another index for quantitative estimation of blood velocity, is proportional to the square of the NB. The SBR is theoretically a more exact measurement which is proportional to velocity, whereas the NB is an approximation. Normalized blur was calculated in earlier versions of LSFG because of technical limitations; the SBR is used in current versions of the LSFG instrument. As these values are in arbitrary units, they should not be used to make comparisons between different eyes or different sites in an eye. Clinical protocols, calibration, evaluation procedures and possible limitations of the LSFG technique are described and the results of ocular blood flow studies using LSFG are briefly summarized. The LSFG method is suitable for monitoring the time–course of change in the tissue circulation at the same site in the same eye at various intervals, ranging from seconds to months. Unresolved issues concern the effect of pupil size on measurement results, the effects of various stimulations, and how to measure choroidal and retinal blood flow velocity separately without using the blue‐component of argon laser.
Role of Sarco/Endoplasmic Reticulum Calcium ATPase in Lower Urinary Tract Smooth Muscles
Authors: KIM Dae Kyung , YOSHIMURA Naoki , TYAGI Pradeep , CHANCELLOR Michael B. 
Published: September 2009

The control of intracellular Ca (2+) is central to the regulation of smooth muscle contractility. A defect in sarco/endoplasmic reticulum calcium ATPase (SERCA) activity and its expression level has been suggested as a major pathology in cardiac dysfunction. Recent studies have demonstrated that the increased expression of SERCA2a improves myocardial contractility and Ca (2+) handling in disease conditions. The therapeutic transfer of SERCA has been tried in an animal heart failure model with promising results.We know that SERCA also plays a major role in regulation of Ca (2+) in detrusor contraction and may affect the functional outcome after outlet obstruction and ischemia/reperfusion injury. Therefore, this may be a new target to improve muscle function in the lower urinary tract. We have performed studies using the application SERCA gene transfer into the rat urethra, demonstrating favorable results for the protection of urethral sphincteric muscle function from vaginal distension‐induced injury. The therapeutic transfer of SERCA may be a novel approach for gene therapy to treat lower urinary tract pathology, including underactive bladder and stress urinary incontinence.
Noninvasive Videourodynamics Using Transperineal Doppler Ultrasonography
Authors: OZAWA Hideo , CHANCELLOR Michael B. , NOSE Hiroyuki , WATANABE Yuichi , YOKOYAMA Teruhiko , SASAKI Katsumi , WATANABE Toyohiko , KUMON Hiromi 
Published: September 2009

A completely noninvasive transperineal urodynamic technique using Doppler ultrasonography has been developed. Because normal urine does not contain blood cells, urine was thought not to produce the Doppler effects. However, basic studies confirmed that the decrease of pressure at high velocity (Bernoulli effect) caused dissolved gas to form microbubbles, which can be detected by Doppler ultrasonography. Subjects were seated and a probe was advanced by remote control to achieve gentle contact with the perineal skin. Digital uroflow data signals and color Doppler ultrasound video images were processed on a personal computer. The flow velocity curves from two sites: the distal prostatic urethra just above the external sphincter (V1) and the sphincteric urethra (V2), were plotted against time. The parameters of the pressure flow studies and the Doppler ultrasound urodynamic studies were compared in men who had various degrees of obstruction.The functional cross‐sectional area at prostatic urethra (A1), which was calculated by Qmax/V1, was lower in the group with bladder outlet obstruction (BOO) versus the control group. The velocity ratio (VR), which was calculated by V1/V2, was the parameter with the best correlation with BOO index; although A1 had a similar correlation. This method is viable for diagnosing the degree of BOO.The development of noninvasive Doppler ultrasound videourodynamics will dramatically add to the knowledge regarding voiding function.
Lower Urinary Tract: Diabetes Mellitus‐focused on Recent Experimental Results
Authors: TORIMOTO Kazumasa , SASAKI Katsumi , MATSUYOSHI Hiroko , MATSUMOTO Yoshihiro , HIRAO Yoshihiko , CHANCELLOR Michael B. , YOSHIMURA Naoki 
Published: September 2009

Historically, it has been widely believed that urologic and neuropathic problems occur as late complications in the disease process of diabetes mellitus (DM). However, there is recent evidence that diabetic neuropathy can occur early in the disease process, with urologic manifestation. In the present article we focus on the complications of DM in the lower urinary tract (diabetic cystopathy and urethropathy).The most important and frustrating issues with diabetic cystopathy are its insidious onset and permanent damage, which have hampered attempted treatments. Recent studies have revealed that neurotrophic/nerve growth factors and nitrergic/adrenergic mechanisms are important for the pathogenesis of diabetic voiding dysfunction. Therefore, the supply of neurotrophic factors and the modulation of nitrergic/adrenergic pathways could be used to restore voiding function in patients with diabetic cystopathy and urethropathy.
Biomechanics of Diabetic Bladders
Authors: WANG Chung Cheng , NAGATOMI Jiro , TOOSI Khashayar K. , YOSHIMURA Naoki , SACKS Michael S. , CHANCELLOR Michael B. 
Published: September 2009

Objectives: Biomechanics is the mechanics applied to biology and we hereby review bladder biomechanics in diabetic bladder dysfunction.Methods: The important mechanical properties of bladder tissue include the stress‐strain relationship, viscoelasticity and active contraction. Using biaxial mechanical testing methods, the diabetic bladders exhibited non‐linear stress‐strain mechanical relationships with increasing stiffness at higher stretches in both circumferential and longitudinal directions.Results: The diabetic bladders showed mechanical anisotropy with a greater compliance in the circumferential direction than in the longitudinal direction. The time‐course study suggested that diuresis mainly contributed to the “early” changes of the mechanical properties with “late” changes induced by other diabetic effects.Conclusion: The biomechanical study of the urinary bladder has offered a novel understanding of the pathophysiology of diabetic cystopathy and we believe the collaboration of urology and engineering will contribute greatly to the treatment of diabetic bladder dysfunction in the future.
ADAPTIVENESS IN MONOTONE PSEUDO-BOOLEAN OPTIMIZATION AND STOCHASTIC NEURAL COMPUTATION
Authors: GROSSI GIULIANO 
Published: September 2009

Hopfield neural network (HNN) is a nonlinear computational model successfully applied in finding near-optimal solutions of several difficult combinatorial problems. In many cases, the network energy function is obtained through a learning procedure so that its minima are states falling into a proper subspace (feasible region) of the search space. However, because of the network nonlinearity, a number of undesirable local energy minima emerge from the learning procedure, significantly effecting the network performance.In the neural model analyzed here, we combine both a penalty and a stochastic process in order to enhance the performance of a binary HNN. The penalty strategy allows us to gradually lead the search towards states representing feasible solutions, so avoiding oscillatory behaviors or asymptotically instable convergence. Presence of stochastic dynamics potentially prevents the network to fall into shallow local minima of the energy function, i.e., quite far from global optimum. Hence, for a given fixed network topology, the desired final distribution on the states can be reached by carefully modulating such process.The model uses pseudo-Boolean functions both to express problem constraints and cost function; a combination of these two functions is then interpreted as energy of the neural network. A wide variety of NP-hard problems fall in the class of problems that can be solved by the model at hand, particularly those having a monotonic quadratic pseudo-Boolean function as constraint function. That is, functions easily derived by closed algebraic expressions representing the constraint structure and easy (polynomial time) to maximize.We show the asymptotic convergence properties of this model characterizing its state space distribution at thermal equilibrium in terms of Markov chain and give evidence of its ability to find high quality solutions on benchmarks and randomly generated instances of two specific problems taken from the computational graph theory.
CHANGES IN LIVESTOCK PROJECTS ON THE BASIS OF ENVIRONMENTAL IMPACT ASSESSMENT SCREENING
Authors: KØRNØV LONE BOTIN , CHRISTENSEN PER 
Published: September 2009

Growing pressures to increase animal production challenge the agricultural sector to identify technologies and solutions that will make livestock production environmentally sound. One mechanism which may assist the sector in meeting this challenge is Environmental Impact Assessment (EIA). On the basis of an evaluation of EIA screenings of Danish livestock, this article presents and discusses how EIA responds to the environmental challenge of intensive livestock projects. The analysis and discussion focus on the changes introduced in livestock projects as a result of the EIA screening process. Screening is normally used for deciding whether or not a project proposal requires an EIA. The article shows how screening also functions as a tool for changing livestock projects, thus being a regulatory instrument in its own right. The analysis of livestock EIA screenings shows that changes are initiated through a wide range of measures mitigating the environmental impacts of particular livestock projects. Fodder optimisation, cover crops, reduced animal pressure, change of crop rotation, repositioning of risk areas and changed design of animal houses are frequently applied measures. As a conclusion, EIA is identified as an important supplement to other regulatory instruments aiming at balancing the benefits and environmental costs of livestock production. However, the article also concludes that the systematic inspection of livestock projects needs to be improved in order to secure that the changes introduced through screening are also robust in character.
EXPLORING THE POTENTIAL FAILURE OF THE REGULATORY FRAMEWORK AND MANAGEMENT TOOLS WHICH GOVERN THE CONSERVATION OF BIODIVERSITY: THE CASE OF ARTIFICIAL LAKE KERKINI IN GREECE
Authors: MANOU DIMITRA , PAPATHANASIOU JASON 
Published: September 2009

This paper was developed in the context of the research project entitled GEMCONBIO (Governance and Ecosystems Management for the Conservation of Biodiversity), which is a European FP6-funded project under Priority 7 — Citizens and Governance in a Knowledge-Based Society. The projects strategic objective is, through the elaboration of certain case studies, to explore the interactions between governance modes and sustainable development objectives in view of identifying which governance processes and institutions can contribute best to the conservation of biodiversity. The case study of Kerkini Lake was selected along with approximately 27 case studies across Europe, the United States and third countries because of the area's very important ecosystem. It is one of the 10 most important wetlands in Greece, a declared National Park and one of the most important wetlands for birds in Europe. There is a plethora of national, European and international laws and regulations as well as administrative decisions regarding the study area. However, problems of implementation and compliance appear to be very strong causing severe implications in the area's sustainable development.
Confounding Effects in “A Six-Gene Signature Predicting Breast Cancer Lung Metastasis”
Authors: Culhane Aedín C. , Quackenbush John 
Published: September 2009

Abstract
The majority of breast cancer deaths result from metastases rather than from direct effects of the primary tumor itself. Recently, Landemaine and colleagues described a six-gene signature purported to predict lung metastasis risk. They analyzed gene expression in 23 metastases from breast cancer patients (5 lung, 18 non-lung) identifying a 21-gene signature. Expression of 16 of these was analyzed in primary breast tumors from 72 patients with known outcome, and six were selected that were predictive of lung metastases: DSC2, TFCP2L1, UGT8, ITGB8, ANP32E, and FERMT1. Despite the value of such a signature, our analysis indicates that this analysis ignored potentially important confounding factors and that their signature is instead a surrogate for molecular subtype. [Cancer Res 2009;69(18):7480–5]
Colorectal Cancer Risk Is Not Associated with Increased Levels of Homozygosity in a Population from the United Kingdom
Authors: Spain Sarah L. , Cazier Jean-Baptiste ,   The CORGI Consortium,, Houlston Richard , Carvajal-Carmona Luis , Tomlinson Ian 
Published: September 2009

Abstract
Genome-wide association studies have identified several common single nucleotide polymorphisms (SNP) associated with an increased risk of colorectal cancer (CRC), although they have failed to identify any recessively acting alleles that contribute to disease risk. However, two recent studies have suggested that inbreeding and runs of homozygosity (ROH) increase the risk of developing cancer, perhaps by exposing recessive alleles as a result of autozygosity. To examine these results in a relatively large case-control series, we analyzed samples from a cohort in the United Kingdom comprising 921 colorectal tumor cases and 929 controls. Individuals were genotyped using a 550,000 tagging SNP panel. Additionally, we identified from these SNPs a set of ∼30,000 SNPs in low pairwise linkage disequilibrium. To determine whether homozygosity was associated with CRC, we performed multiple tests to assess homozygosity at individual SNPs and ROHs in cases and controls. No association was found between CRC and (i) homozygosity at any individual SNP, (ii) overall homozygosity or level of inbreeding, (iii) total length or number of ROHs per individual, or (iv) a ROH at any particular genomic location. In conclusion, our results from a large case-control series do not replicate those of previous studies and suggest that homozygosity/autozygosity is not a major risk factor for CRC in an outbred population. [Cancer Res 2009;69(18):7422–9]
Integrative Transcriptome Analysis Reveals Common Molecular Subclasses of Human Hepatocellular Carcinoma
Authors: Hoshida Yujin , Nijman Sebastian M.B. , Kobayashi Masahiro , Chan Jennifer A. , Brunet Jean-Philippe , Chiang Derek Y. , Villanueva Augusto , Newell Philippa , Ikeda Kenji , Hashimoto Masaji , Watanabe Goro , Gabriel Stacey , Friedman Scott L. , Kumada Hiromitsu , Llovet Josep M. , Golub Todd R. 
Published: September 2009

Abstract
Hepatocellular carcinoma (HCC) is a highly heterogeneous disease, and prior attempts to develop genomic-based classification for HCC have yielded highly divergent results, indicating difficulty in identifying unified molecular anatomy. We performed a meta-analysis of gene expression profiles in data sets from eight independent patient cohorts across the world. In addition, aiming to establish the real world applicability of a classification system, we profiled 118 formalin-fixed, paraffin-embedded tissues from an additional patient cohort. A total of 603 patients were analyzed, representing the major etiologies of HCC (hepatitis B and C) collected from Western and Eastern countries. We observed three robust HCC subclasses (termed S1, S2, and S3), each correlated with clinical parameters such as tumor size, extent of cellular differentiation, and serum α-fetoprotein levels. An analysis of the components of the signatures indicated that S1 reflected aberrant activation of the WNT signaling pathway, S2 was characterized by proliferation as well as MYC and AKT activation, and S3 was associated with hepatocyte differentiation. Functional studies indicated that the WNT pathway activation signature characteristic of S1 tumors was not simply the result of β-catenin mutation but rather was the result of transforming growth factor-β activation, thus representing a new mechanism of WNT pathway activation in HCC. These experiments establish the first consensus classification framework for HCC based on gene expression profiles and highlight the power of integrating multiple data sets to define a robust molecular taxonomy of the disease. [Cancer Res 2009;69(18):7385–92]
Phosphatidylinositol 3′-Kinase Catalytic Subunit α Gene Amplification Contributes to the Pathogenesis of Mantle Cell Lymphoma
Authors: Psyrri Amanda , Papageorgiou Sotirios , Liakata Elisavet , Scorilas Andreas , Rontogianni Dimitra , Kontos Christos K. , Argyriou Pinelopi , Pectasides Dimitrios , Harhalakis Nikolaos , Pappa Vassiliki , Kolialexi Aggeliki , Economopoulou Christina , Kontsioti Frida , Maratou Eirini , Dimitriadis George , Economopoulou Panagiota , Economopoulos Theofanis 
Published: September 2009

Abstract
Purpose: Activation of phosphatidylinositol 3′-kinase pathway is implicated in the pathogenesis of mantle cell lymphoma (MCL). The genetic change in phosphatidylinositol 3′-kinase catalytic subunit α (PIK3CA) in MCL has not been identified.
Experimental Design: Thirty-five primary MCL cases and 2 MCL cell lines (GRANTA-519 and Rec-1) were used to investigate somatic mutation and gene copy number of PIK3CA. Gene copy number was determined using quantitative real-time PCR and fluorescence in situ hybridization. We used quantitative real-time reverse transcription-PCR to measure PIK3CA transcription levels. Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) and phoshorylated AKT protein levels were analyzed using Western blotting and immunohistochemistry. Flow cytometry was used to assess apoptosis after treatment of MCL cell lines and one control cell line with LY294002, a specific inhibitor of PI3KCA.
Results: Fifteen of 22 (68%) MCL cases and the MCL cell lines harbored a gain (≥3) of PIK3CA gene copy number. In addition, cases with increased PIK3CA gene copy number had elevated PIK3CA mRNA levels. Furthermore, amplification of PIK3CA correlated with the status of AKT phosphorylation in 7 of 12 (58%) primary MCL cases. Inhibition of PIK3CA induced increased apoptosis in the MCL cell lines. PTEN protein expression was present in all 14 primary MCL cases and cell lines by Western blotting, whereas 5 of 33 (15%) cases tested by immunohistochemistry had loss of PTEN expression.
Conclusions: We conclude that a gain of gene copy number of PIK3CA is frequent genetic alteration that contributes to MCL progression. PIK3CA is a promising therapeutic target in MCL. (Clin Cancer Res 2009;15(18):5724–32)
Ethnic Differences and Functional Analysis of MET Mutations in Lung Cancer
Authors: Krishnaswamy Soundararajan , Kanteti Rajani , Duke-Cohan Jonathan S. , Loganathan Sivakumar , Liu Wanqing , Ma Patrick C. , Sattler Martin , Singleton Patrick A. , Ramnath Nithya , Innocenti Federico , Nicolae Dan L. , Ouyang Zheng , Liang Jie , Minna John , Kozloff Mark F. , Ferguson Mark K. , Natarajan Viswanathan , Wang Yi-Ching , Garcia Joe G.N. , Vokes Everett E. , Salgia Ravi 
Published: September 2009

Abstract
Purpose: African Americans have higher incidence and poorer response to lung cancer treatment compared with Caucasians. However, the underlying molecular mechanisms for the significant ethnic difference are not known. The present study examines the ethnic differences in the type and frequency of MET proto-oncogene (MET) mutation in lung cancer and correlated them with other frequently mutated genes such as epidermal growth factor receptor (EGFR), KRAS2, and TP53.
Experimental Design: Using tumor tissue genomic DNA from 141 Asian, 76 Caucasian, and 66 African American lung cancer patients, exons coding for MET and EGFR were PCR amplified, and mutations were detected by sequencing. Mutation carriers were further screened for KRAS2 and TP53 mutations. Functional implications of important MET mutations were explored by molecular modeling and hepatocyte growth factor binding studies.
Results: Unlike the frequently encountered somatic mutations in EGFR, MET mutations in lung tumors were germline. MET-N375S, the most frequent mutation of MET, occurred in 13% of East Asians compared with none in African Americans. The frequency of MET mutations was highest among male smokers and squamous cell carcinoma. The MET-N375S mutation seems to confer resistance to MET inhibition based on hepatocyte growth factor ligand binding, molecular modeling, and apoptotic susceptibility to MET inhibitor studies.
Conclusions: MET in lung cancer tissues contained nonsynonymous mutations in the semaphorin and juxtamembrane domains but not in the tyrosine kinase domain. All the MET mutations were germline. East Asians, African-Americans, and Caucasians had different MET genotypes and haplotypes. MET mutations in the semaphorin domain affected ligand binding. (Clin Cancer Res 2009;15(18):5714–23)