bluuebunny/crossref_metadata_2025 huggingface dataset:
Blind Deconvolution of the Aortic Pressure Waveform Using the Malliavin Calculus
Authors: Abutaleb Ahmed S. , Waheed M. El-Sayed , Elhamy Nermeen M.
Published: September 2010

Multichannel Blind Deconvolution (MBD) is a powerful tool particularly for the identification and estimation of dynamical systems in which a sensor, for measuring the input, is difficult to place. This paper presents an MBD method, based on the Malliavin calculus MC (stochastic calculus of variations). The arterial network is modeled as a Finite Impulse Response (FIR) filter with unknown coefficients. The source signal central arterial pressure CAP is also unknown. Assuming that many coefficients of the FIR filter are time‐varying, we have been able to get accurate estimation results for the source signal, even though the filter order is unknown. The time‐varying filter coefficients have been estimated through the proposed Malliavin calculus‐based method. We have been able to deconvolve the measurements and obtain both the source signal and the arterial path or filter. The presented examples prove the superiority of the proposed method, as compared to conventional methods.
Direct Computation of Operational Matrices for Polynomial Bases
Authors: Guimarães Osvaldo , Piqueira José Roberto C. , Lobo Netto Marcio
Published: September 2010

Several numerical methods for boundary value problems use integral and differential operational matrices, expressed in polynomial bases in a Hilbert space of functions. This work presents a sequence of matrix operations allowing a direct computation of operational matrices for polynomial bases, orthogonal or not, starting with any previously known reference
matrix. Furthermore, it shows how to obtain the reference matrix for a chosen polynomial base. The results presented here can be applied not only for integration and differentiation, but also for any linear operation.
Video-Assisted Thyroidectomy for Papillary Thyroid Carcinoma
Authors: Lombardi Celestino Pio , Raffaelli Marco , De Crea Carmela , D'Amore Annamaria , Oragano Luigi , Salvatori Massimo , Bellantone Rocco
Published: September 2010

Background. The results of video-assisted thyroidectomy (VAT) were evaluated in a large series of patients with papillary thyroid carcinoma (PTC), especially in terms of completeness of the surgical resection and short-to-medium term recurrence.Methods. The medical records of all patients who underwent video-assisted thyroidectomy for PTC between June 1998 and May 2009 were reviewed.Results. Three hundred fifty-nine patients were included. One hundred twenty-six patients underwent concomitant central neck node removal. Final histology showed 285 pT1, 26 pT2, and 48 pT3 PTC. Lymph node metastases were found in 27 cases. Follow-up was completed in 315 patients. Mean postoperative serum thyroglobulin level off levothyroxine was 5.4 ng/mL. Post operative ultrasonography showed no residual thyroid tissue in all the patients. Mean post-operative131I uptake was 1.7%. One patient developed lateral neck recurrence. No other recurrence was observed.
Structure and Characterization of Vertically Aligned Single‐Walled Carbon Nanotube Bundles
Authors: Márquez Francisco , López Vicente , Morant Carmen , Roque-Malherbe Rolando , Domingo Concepción , Elizalde Eduardo , Zamora Félix
Published: September 2010

Arrays of vertically aligned single‐walled carbon nanotube bundles, SWCNTs, have been synthesized by simple alcohol catalytic chemical vapor deposition process, carried out at 800 ∘C. The formed SWCNTs are organized in small groups perpendicularly aligned and attached to the substrate. These small bundles show a constant diameter of ca. 30 nm and are formed by the adhesion of no more than twenty individual SWCNTs perfectly aligned along their length.
Quantitation by Portable Gas Chromatography: Mass Spectrometry of VOCs Associated with Vapor Intrusion
Authors: Fair Justin D. , Bailey William F. , Felty Robert A. , Gifford Amy E. , Shultes Benjamin , Volles Leslie H.
Published: September 2010

Development of a robust reliable technique that permits for the rapid quantitation of volatile organic chemicals is an important first step to remediation associated with vapor intrusion. This paper describes the development of an analytical method that allows for the rapid and precise identification and quantitation of halogenated and nonhalogenated contaminants commonly found within the ppbv level at sites where vapor intrusion is a concern.
On Maximal Ideals of Compact Connected Topological Semigroups
Authors: McLaughlin Phoebe , So Shing S. , Wang Haohao
Published: September 2010

Several results concerning ideals of a compact topological semigroup S with S2 = S can be found in the literature.
In this paper, we further investigate in a compact connected topological semigroup S how the conditions S2 = S and S2 ≠ S affect
the structure of ideals of S, especially the maximal ideals.
Ground-Penetrating Radar Evaluation of Moisture and Frost across Typical Saskatchewan Road Soils
Authors: Berthelot Curtis , Podborochynski Diana , Saarenketo Timo , Marjerison Brent , Prang Colin
Published: September 2010

This study was undertaken to evaluate the effect of soil type, moisture content, and the presence of frost on road substructure permittivity. Permittivity sensitivity of typical road soils was characterized in the laboratory to provide baseline dielectric constant values which were compared to field ground penetrating radar (GPR) survey results. Both laboratory devices, the complex dielectric network analyzer and the Adek Percometer, as well as the field GPR system were used in this study to measure the dielectric constant of soils. All three systems differentiated between coarse-grained and fine grained soils. In addition, at temperatures below freezing, all three systems identified an increase in water content in soils; however, when frozen, the sensitivity of dielectric constant across soil type and moisture content was significantly reduced. Based on the findings of this study, GPR technology has the ability to characterize in situ substructure soil type and moisture content of typical Saskatchewan road substructure soils. Given the influence of road soil type and moisture content on in-service road performance, this ability could provide road engineers with accurate estimates of in situ structural condition of road structures for preservation and rehabilitation planning and optimization purposes.
Some Remarks on Diffusion Distances
Authors: Goldberg Maxim J. , Kim Seonja
Published: September 2010

As a diffusion distance, we propose to use a metric (closely related to cosine similarity) which is defined as the L2 distance between two L2‐normalized vectors. We provide a mathematical explanation as to why the normalization makes diffusion distances more meaningful. Our proposal is in contrast to that made some years ago by R. Coifman which finds the L2 distance between certain L1 unit vectors. In the second part of the paper, we give two proofs that an extension of mean first passage time to mean first passage cost satisfies the triangle inequality; we do not assume that the underlying Markov matrix is diagonalizable. We conclude by exhibiting an interesting connection between the (normalized) mean first passage time and the discretized solution of a certain Dirichlet‐Poisson problem and verify our result numerically for the simple case of the unit circle.
Toll-Like Receptor 3 in Liver Diseases
Authors: Yin Shi , Gao Bin
Published: September 2010

Toll-like receptor 3 (TLR3) is a member of the TLR family that can recognize double-stranded RNA (dsRNA), playing an important role in antiviral immunity. Recent studies have shown that TLR3 is also expressed on parenchymal and nonparenchymal cells in the liver as well as on several types of immune cells. In this review, we summarize the role of TLR3 in liver injury, inflammation, regeneration, and liver fibrosis, and discuss the implication of TLR3 in the pathogenesis of human liver diseases including viral hepatitis and autoimmune liver disease.
Shaolin Dan Tian Breathing Fosters Relaxed and Attentive Mind: A Randomized Controlled Neuro‐Electrophysiological Study
Authors: Chan Agnes S. , Cheung Mei-Chun , Sze Sophia L. , Leung Winnie Wing-Man , Shi Dejian
Published: September 2010

Neuro‐electrophysiological studies on meditative breathing revealed its association with either a
relaxed or an attentive state. The present study aimed to investigate whether the Shaolin Dan
Tian Breathing (DTB) technique, which consists of the Passive and Active subtypes and can be
considered as a relaxation exercise and Qigong, would induce both relaxed and attentive states.
Twenty‐two adults and 22 age‐, gender‐ and education‐matched controls received training on the
Shaolin DTB (experimental group) and the progressive muscle relaxation respectively for one
month. Eyes‐closed resting EEG data before and immediately after each type of breathing were
obtained individually at baseline and after one‐month training. At baseline, the EEG changes
after the Shaolin DTB between both groups were comparable. After one‐month training,
participants in the experimental, but not the control, group showed enhanced temporal alpha
asymmetry (an index of relaxation and positive mood) after performing the Passive DTB for five
minutes, and enhanced intra‐ and inter‐hemispheric theta coherence (an index of attention and
alertness) after performing the Active DTB. The present findings suggested a positive effect of
the Shaolin DTB technique on enhancing human neural activity and connectivity, which may
possibly enhance mood state and cognitive functions.
Simple Synthesis of Flower-Likeln2S3Structures and Their Use as Templates to Prepare CuS Particles
Authors: Sheng Xia , Wang Lei , Chen Guanbi , Yang Deren
Published: September 2010

Flower-like structureIn2S3particles are prepared by a simple and rapid method. The reaction proceeds in a polyalcohol system without using any complex precursors. The phase and morphology of theIn2S3are investigated. Furthermore, flower-like structure CuS particles are synthesized via the reaction ofCu2+ions with the obtainedIn2S3as templates. Both theIn2S3and CuS particles can be used in preparing compound solar cell materialCuInS2.
Caustics, Cold Flows, and Annual Modulation
Authors: Natarajan Aravind
Published: September 2010

We discuss the formation of dark matter caustics, and their possible detection by future dark matter experiments. The annual modulation expected in the recoil rate measured by a dark matter detector is discussed. We consider the example of dark matter particles with a Maxwell-Boltzmann velocity distribution modified by a cold stream due to a nearby caustic. It is shown that the effect of the caustic flow is potentially detectable, even when the density enhancement due to the caustic is small. This makes the annual modulation effect an excellent probe of inner caustics. We also show that the phase of the annual modulation at low recoil energies does not constrain the particle mass unless the velocity distribution of particles in the solar neighborhood is known.
Benefits of Subliminal Feedback Loops in Human-Computer Interaction
Authors: Ritter Walter
Published: September 2010

A lot of efforts have been directed to enriching human-computer interaction to make the user experience more pleasing or efficient. In this paper, we briefly present work in the fields of subliminal perception and affective computing, before we outline a new approach to add analog communication channels to the human-computer interaction experience. In this approach, in addition to symbolic predefined mappings of input to output, a subliminal feedback loop is used that provides feedback in evolutionary subliminal steps. In two studies involving concentration-intensive games, we investigated the impact of this approach. In a first study evolutionary feedback loops adjusted the user interface of a memory game whereas in the second study the lighting of the test room was adjusted dynamically. The results show that in settings with an evolutionary feedback loop test participants were able to reach significantly higher scores compared to the static counterparts. Finally, we discuss the impact that such subliminally working applications might have on the user's acceptance.
A Case of Cystic Basal Cell Carcinoma Which Shows a Homogenous Blue/Black Area under Dermatoscopy
Authors: Yoneta Akihiro , Horimoto Kohei , Nakahashi Keiko , Mori Satoru , Maeda Kazuo , Yamashita Toshiharu
Published: September 2010

Basal cell carcinoma (BCC) is the most common skin tumor and contains several different histopathological types. Here, we report a case of cystic basal cell carcinoma, which is relatively rare and might be clinically misdiagnosed. A dermatoscopic examination of the case revealed a homogenous blue/black area usually not seen in BCC. We reviewed 102 BCC cases resected and diagnosed at Sapporo Medical University Hospital between April 2005 and March 2010. Among them, only three were the cystic type.
Comparative Effects of Acupressure at Local and Distal Acupuncture Points on Pain Conditions and Autonomic Function in Females with Chronic Neck Pain
Authors: Matsubara Takako , Arai Young-Chang P. , Shiro Yukiko , Shimo Kazuhiro , Nishihara Makoto , Sato Jun , Ushida Takahiro
Published: September 2010

Acupressure on local and distal acupuncture points might result in sedation and relaxation, thereby reducing chronic neck pain. The aim was to investigate the effect of acupressure at local (LP) and distal acupuncture points (DP) in females with chronic neck pain. Thirty‐three females were assigned to three groups: the control group did not receive any stimuli, the LP group received acupressure at local acupuncture points, GB 21, SI 14 and SI 15, and the DP group received acupressure at distal acupuncture points, LI 4, LI 10 and LI 11. Verbal rating scale (VRS), Neck Disability Index (NDI), State‐Trait Anxiety Inventory (STAI), muscle hardness (MH), salivary alpha‐amylase (sAA) activity, heart rate (HR), heart rate variability (HRV) values and satisfaction due to acupressure were assessed. VRS, NDI, STAI and MH values decreased after acupressure in the LP and the DP group. HR decreased and the power of high frequency (HF) component of HRV increased after acupressure in only the LP group. Although acupressure on not only the LP but also the DP significantly improved pain conditions, acupressure on only the LP affected the autonomic nervous system while acupuncture points per se have different physical effects according to location.
Hyperpolarized 13C Spectroscopic Imaging Informs on Hypoxia-Inducible Factor-1 and Myc Activity Downstream of Platelet-Derived Growth Factor Receptor
Authors: Dafni Hagit , Larson Peder E.Z. , Hu Simon , Yoshihara Hikari A.I. , Ward Christopher S. , Venkatesh Humsa S. , Wang Chunsheng , Zhang Xiaoliang , Vigneron Daniel B. , Ronen Sabrina M.
Published: September 2010

The recent development of hyperpolarized 13C magnetic resonance spectroscopic imaging provides a novel method for in vivo metabolic imaging with potential applications for detection of cancer and response to treatment. Chemotherapy-induced apoptosis was shown to decrease the flux of hyperpolarized 13C label from pyruvate to lactate due to depletion of NADH, the coenzyme of lactate dehydrogenase. In contrast, we show here that in PC-3MM2 tumors, inhibition of platelet-derived growth factor receptor with imatinib reduces the conversion of hyperpolarized pyruvate to lactate by lowering the expression of lactate dehydrogenase itself. This was accompanied by reduced expression of vascular endothelial growth factor and glutaminase, and is likely mediated by reduced expression of their transcriptional factors hypoxia-inducible factor-1 and c-Myc. Our results indicate that hyperpolarized 13C MRSI could potentially detect the molecular effect of various cell signaling inhibitors, thus providing a radiation-free method to predict tumor response. Cancer Res; 70(19); 7400–10. ©2010 AACR.
Evidence of an Adaptive Response Targeting DNA Nonhomologous End Joining and Its Transmission to Bystander Cells
Authors: Klammer Holger , Kadhim Munira , Iliakis George
Published: September 2010

Adaptive response (AR) is a term describing resistance to ionizing radiation–induced killing or formation of aberrant chromosomes that is mediated by pre-exposure to low ionizing radiation doses. The mechanism of AR remains elusive. Because cell killing and chromosome aberration formation derive from erroneous processing of DNA double-strand breaks (DSB), AR may reflect a modulation of DSB processing by nonhomologous end joining (NHEJ) or homologous recombination repair. Here, we use plasmid end-joining assays to quantify modulations induced by low ionizing radiation doses to NHEJ, the dominant pathway of DSB repair in higher eukaryotes, and investigate propagation of this response through medium transfer to nonirradiated bystander cells. Mouse embryo fibroblasts were conditioned with 10 to 1000 mGy and NHEJ quantified at different times thereafter by challenging with reporter plasmids containing a DSB. We show robust increases in NHEJ efficiency in mouse embryo fibroblasts exposed to ionizing radiation >100 mGy, irrespective of reporter plasmid used. Human tumor cells also show AR of similar magnitude that is compromised by caffeine, an inhibitor of DNA damage signaling acting by inhibiting ATM, ATR, and DNA-PKcs. Growth medium from pre-irradiated cells induces a caffeine-sensitive AR in nonirradiated cells, similar in magnitude to that seen in irradiated cells. In bystander cells, γH2AX foci are specifically detected in late S-G2 phase and are associated with Rad51 foci that signify the function of homologous recombination repair, possibly on DNA replication–mediated DSBs. The results point to enhanced NHEJ as a mechanism of AR and suggest that AR may be transmitted to bystander cells through factors generating replication-mediated DSBs. Cancer Res; 70(21); 8498–506. ©2010 AACR.
AXL Is an Essential Factor and Therapeutic Target for Metastatic Ovarian Cancer
Authors: Rankin Erinn B. , Fuh Katherine C. , Taylor Tiffany E. , Krieg Adam J. , Musser Margaret , Yuan Jenny , Wei Kevin , Kuo Calvin J. , Longacre Teri A. , Giaccia Amato J.
Published: September 2010

The receptor tyrosine kinase AXL is thought to play a role in metastasis; however, the therapeutic efficacy of an AXL-targeting agent remains largely untested in metastatic disease. In this study, we defined AXL as a therapeutic target for metastatic ovarian cancer. AXL is primarily expressed in metastases and advanced-stage human ovarian tumors but not in normal ovarian epithelium. Genetic inhibition of AXL in human metastatic ovarian tumor cells is sufficient to prevent the initiation of metastatic disease in vivo. Mechanistically, inhibition of AXL signaling in animals with metastatic disease results in decreased invasion and matrix metalloproteinase activity. Most importantly, soluble human AXL receptors that imposed a specific blockade of the GAS6/AXL pathway had a profound inhibitory effect on progression of established metastatic ovarian cancer without normal tissue toxicity. These results offer the first genetic validation of GAS6/AXL targeting as an effective strategy for inhibition of metastatic tumor progression in vivo. Furthermore, this study defines the soluble AXL receptor as a therapeutic candidate agent for treatment of metastatic ovarian cancer, for which current therapies are ineffective. Cancer Res; 70(19); 7570–9. ©2010 AACR.
Metabolic Aggressiveness in Benign Meningiomas with Chromosomal Instabilities
Authors: Monleón Daniel , Morales José Manuel , Gonzalez-Segura Ana , Gonzalez-Darder José Manuel , Gil-Benso Rosario , Cerdá-Nicolás Miguel , López-Ginés Concepción
Published: September 2010

Meningiomas are often considered benign tumors curable by surgery, but most recurrent meningiomas correspond to histologic benign tumors. Because alterations in chromosome 14 among others have suggested clinical aggressiveness and recurrence, determining both the molecular phenotype and the genetic profile may help distinguish tumors with aggressive metabolism. The aim of this study was to achieve higher specificity in the detection of meningioma subgroups by measuring chromosomal instabilities by fluorescence in situ hybridization and cytogenetics and metabolic phenotypes by high-resolution magic angle spinning spectroscopy. We studied 46 meningioma biopsies with these methodologies. Of these, 34 were of WHO grade 1 and 12 were of WHO grade 2. Genetic analysis showed a subgroup of histologic benign meningioma with chromosomal instabilities. The metabolic phenotype of this subgroup indicated an aggressive metabolism resembling that observed for atypical meningioma. According to the metabolic profiles, these tumors had increased energy demand, higher hypoxic conditions, increased membrane turnover and cell proliferation, and possibly increased resistance to apoptosis. Taken together, our results identify distinct metabolic phenotypes for otherwise benign meningiomas based on cytogenetic studies and global metabolic profiles of intact tumors. Measuring the metabolic phenotype of meningioma intact biopsies at the same time as histopathologic analysis may allow the early detection of clinically aggressive tumors. Cancer Res; 70(21); 8426–34. ©2010 AACR.
Hypoxia in Models of Lung Cancer: Implications for Targeted Therapeutics
Authors: Graves Edward E. , Vilalta Marta , Cecic Ivana K. , Erler Janine T. , Tran Phuoc T. , Felsher Dean , Sayles Leanne , Sweet-Cordero Alejandro , Le Quynh-Thu , Giaccia Amato J.
Published: September 2010

Purpose: To efficiently translate experimental methods from bench to bedside, it is imperative that laboratory models of cancer mimic human disease as closely as possible. In this study, we sought to compare patterns of hypoxia in several standard and emerging mouse models of lung cancer to establish the appropriateness of each for evaluating the role of oxygen in lung cancer progression and therapeutic response.

Experimental Design: Subcutaneous and orthotopic human A549 lung carcinomas growing in nude mice as well as spontaneous K-ras or Myc-induced lung tumors grown in situ or subcutaneously were studied using fluorodeoxyglucose and fluoroazomycin arabinoside positron emission tomography, and postmortem by immunohistochemical observation of the hypoxia marker pimonidazole. The response of these models to the hypoxia-activated cytotoxin PR-104 was also quantified by the formation of γH2AX foci in vitro and in vivo. Finally, our findings were compared with oxygen electrode measurements of human lung cancers.

Results: Minimal fluoroazomycin arabinoside and pimonidazole accumulation was seen in tumors growing within the lungs, whereas subcutaneous tumors showed substantial trapping of both hypoxia probes. These observations correlated with the response of these tumors to PR-104, and with the reduced incidence of hypoxia in human lung cancers relative to other solid tumor types.

Conclusions: These findings suggest that in situ models of lung cancer in mice may be more reflective of the human disease, and encourage judicious selection of preclinical tumor models for the study of hypoxia imaging and antihypoxic cell therapies. Clin Cancer Res; 16(19); 4843–52. ©2010 AACR.
CD44: A Cancer Stem Cell–Related Biomarker with Predictive Potential for Radiotherapy
Authors: Baumann Michael , Krause Mechthild
Published: September 2010

CD44, a cancer stem cell (CSC)-related surface marker, correlates with local control after radiotherapy of early laryngeal cancer. For the first time, a CSC-related marker has been functionally validated for radiotherapy in patients. CD44 expression bears the potential to predict the outcome of radiotherapy by assessment of CSC density. Clin Cancer Res; 16(21); 5091–3. ©2010 AACR.
Monitoring Molecular-Specific Pharmacodynamics of Rapamycin In vivo with Inducible Gal4→Fluc Transgenic Reporter Mice
Authors: Pan Mei-Hsiu , Lin Jeffrey , Prior Julie L. , Piwnica-Worms David
Published: September 2010

Rapamycin (Rap), a small-molecule inhibitor of mTOR, is an immunosuppressant, and several Rap analogues are cancer chemotherapeutics. Further pharmacologic development will be significantly facilitated if in vivo reporter models are available to enable monitoring of molecular-specific pharmacodynamic actions of Rap and its analogues. Herein we present the use of a Gal4→Fluc reporter mouse for the study of Rap-induced mTOR/FKBP12 protein-protein interactions in vivo with the use of a mouse two-hybrid transactivation strategy, a derivative of the yeast two-hybrid system applied to live mice. Upon treatment with Rap, a bipartite transactivator was reconstituted, and transcription of a genomic firefly luciferase reporter was activated in a concentration-dependent (Kd = 2.3 nmol/L) and FK506-competitive (Ki = 17.1 nmol/L) manner in cellulo, as well as in a temporal and specific manner in vivo. In particular, after a single dose of Rap (4.5 mg/kg, i.p.), peak Rap-induced protein-protein interactions were observed in the liver at 24 hours post treatment, with photon flux signals 600-fold over baseline, which correlated temporally with suppression of p70S6 kinase activity, a downstream effector of mTOR. The Gal4→Fluc reporter mouse provides an intact physiologic system to interrogate protein-protein interactions and molecular-specific pharmacodynamics during drug discovery and lead characterization. Imaging protein interactions and functional proteomics in whole animals in vivo may serve as a basic tool for screening and mechanism-based analysis of small molecules targeting specific protein-protein interactions in human diseases. Mol Cancer Ther; 9(10); 2752–60. ©2010 AACR.
Targeted Delivery of Saporin Toxin by Monoclonal Antibody to the Transcobalamin Receptor, TCblR/CD320
Authors: Quadros Edward V. , Nakayama Yasumi , Sequeira Jeffrey M.
Published: September 2010

Cellular uptake of cobalamin (Cbl) occurs by endocytosis of transcobalamin saturated with Cbl by the transcobalamin receptor (TCblR/CD320). The cell cycle–associated overexpression of this receptor in many cancer cells provides a suitable target for delivering chemotherapeutic drugs and cytotoxic molecules to these cells while minimizing the effect on the normal cell population. We have used monoclonal antibodies to the extracellular domain of TCblR to deliver saporin-conjugated secondary antibody to various cell lines propagating in culture. A molar ratio of 2.5:10 nmol/L of primary:secondary antibody concentration was identified as the lowest concentration needed to produce the optimum cytotoxic effect. The effect was more pronounced when cells were seeded at lower density, suggesting lack of cell division in a fraction of the cells at higher density as the likely explanation. Cells in suspension culture, such as K562 and U266 cells, were more severely affected than adherent cultures, such as SW48 and KB cells. This differential effect of the anti–TCblR-saporin antibody conjugate and the ability of an anti-TCblR antibody to target proliferating cells were further evident by the virtual lack of any effect on primary skin fibroblasts and minimal effect on bone marrow cells. These results indicate that preferential targeting of some cancer cells could be accomplished through the TCblR. Mol Cancer Ther; 9(11); 3033–40. ©2010 AACR.
Hsp27 Protects Adenocarcinoma Cells from UV-Induced Apoptosis by Akt and p21-Dependent Pathways of Survival
Authors: Kanagasabai Ragu , Karthikeyan Krishnamurthy , Vedam Kaushik , Qien Wang , Zhu Qianzheng , Ilangovan Govindasamy
Published: September 2010

Transcriptional activation of p53 target genes, due to DNA damage, causes either apoptosis or survival by cell cycle arrest and DNA repair. However, the regulators of the choice between cell death and survival signaling have not been completely elucidated. Here, we report that human adenocarcinoma cells (MCF-7) survive UV-induced DNA damage by heat shock protein 27 (Hsp27)–assisted Akt/p21 phosphorylation/translocation. Protein levels of the p53 target genes, such as p21, Bcl-2, p38MAPK, and Akt, showed a positive correlation to Hsp27 level during 48 hours postirradiation, whereas p53 expression increased initially but started decreasing after 12 hours. Hsp27 prevented the G1-S phase cell cycle arrest, observed after 8 hours of post–UV irradiation, and PARP-1 cleavage was inhibited. Conversely, silencing Hsp27 enhanced G1-S arrest and cell death. Moreover, use of either Hsp27 or Akt small interference RNA reduced p21 phosphorylation and enhanced its retention in nuclei even after 48 hours postirradiation, resulting in enhanced cell death. Our results showed that Hsp27 expression and its direct chaperoning interaction increases Akt stability, and p21 phosphorylation and nuclear-to-cytoplasm translocation, both essential effects for the survival of UV-induced DNA-damaged cells. We conclude that the role of Hsp27 in cancer is not only for enhanced p53 proteolysis per se, rather it is also a critical determinant in p21 phosphorylation and translocation. Mol Cancer Res; 8(10); 1399–412. ©2010 AACR.
Association of Busulfan and Cyclophosphamide Conditioning with Sleep Disorders after Hematopoietic Stem Cell Transplantation
Authors: Faulhaber Gustavo A.M. , Furlanetto Tania W. , Astigarraga Claudia C. , Moser Filho Humberto Luiz , Paludo Angela Paula , Silla Lucia M.R.
Published: September 2010

New indications and conditioning regimens for hematopoietic stem cell transplantation (HSCT) have emerged in the last 10 years. Previous studies have shown the association of HSCT with late effects such as sleep disorders. The aim of this study was to determine the prevalence and factors associated with sleep disorders following HSCT in a population considering these new trends. Sixty-one individuals 1–10 years after allogeneic HSCT were surveyed using the DSM-IV-TR criteria for sleep disorders. Factors related to conditioning and graft-versus-host disease were collected from medical records. A prevalence of sleep disorders of 26.2% was found. Busulfan-cyclophosphamide conditioning was an independent risk factor in a multivariate analysis (relative risk, RR: 3.74, 95% CI: 1.1–12.6; p = 0.03), which also included sex (RR: 2.37, 95% CI: 1.0–5.7; p = 0.05) and age (RR: 1.03, 95% CI: 0.99–1.07; p = 0.11). Sleep disorders were frequent following HSCT. Patients who were treated with busulfan-cyclophosphamide had a higher risk of developing this complication. Female sex was also possibly a risk factor.
Association of Seminal Plasma Motility Inhibitors/Semenogelins with Sperm in Asthenozoospermia-Infertile Men
Authors: Terai K. , Yoshida K. , Yoshiike M. , Fujime M. , Iwamoto T.
Published: September 2010

Seminal plasma motility inhibitors (SPMIs) are proteinase-resistant fragments of semenogelin I and II (Sgs), which are the major proteins of semen coagulum. SPMIs inhibit the motility of spermatozoa, and Sgs are thought to be natural regulators of human sperm function. The mechanism underlying sperm motility regulation and its association with defective motility in infertile men remain unclear. The purpose of this study was to investigate the association between SPMIs and spermatozoa in infertile men with asthenozoospermia. Fifty-four semen samples from 37 asthenozoospermic patients and 17 samples from 9 normal healthy subjects were analyzed. Spermatozoa, washed by Percoll density gradients, were immunostained with anti-SPMI antibody and subjected to flow cytometric analysis. The proportion of spermatozoa labeled with the antibody and the average intensity of fluorescence labeling per spermatozoa were analyzed in relation to the parameters used for semen analysis. A significant negative correlation was found between sperm motility and the proportion (R = –0.68) and intensity (R = –0.38) of labeling. These results suggest that SPMIs remain on the sperm surface after liquefaction. This might account for some disorders of sperm motility observed in infertile men with asthenozoospermia.
Outcomes of Radical Prostatectomy in Clinically Locally Advanced N0M0 Prostate Cancer
Authors: Mearini Luigi , Zucchi Alessandro , Costantini Elisabetta , Bini Vittorio , Nunzi Elisabetta , Porena Massimo
Published: September 2010

Introduction: Radical prostatectomy (RP) in patients with locally advanced (cT3) prostate cancer (PCa) is considered an optional therapy. Aim: To evaluate outcomes of surgery for cT3 disease and to compare results with those of patients treated for cT1–T2 PCa. Patients and Methods: Data of 74 consecutive patients with cT3 N0M0 PCa who underwent RP were compared to those of 425 consecutive unselected patients who underwent surgery for cT1–T2 N0M0 disease. Results: cT3: The pathological report showed a pathological downstaging in 16.3% of cases. Continence rate was 65.5%, potency rate was 38.8%, 5-year PSA-free survival was 61.9%, 5-year cancer-specific survival was 95.2%. cT1–T2: The pathological report showed a clinical downstaging in 39.1%. Continence rate was 70.8%, potency rate was 56.2%, 5-year PSA-free survival was 67.4%, 5-year cancer-specific survival was 96.0%. Conclusions: cT3 PCa presents challenges for the uro-oncologist since standard treatment is still under debate. RP in well-informed patients is a procedure with acceptable morbidity and should be at least a first part of a multimodality approach.
The Unusual History and the Urological Applications of Botulinum Neurotoxin
Authors: Hanchanale Vishwanath S. , Rao Amrith Raj , Martin Francis L. , Matanhelia Shyam S.
Published: September 2010

Introduction: Botulinum neurotoxin (BoNT) is probably the most potent biological toxin that can affect humans. Since its discovery by Justinus Kerner, BoNT has seen use in a wide range of cosmetic and non-cosmetic conditions such as cervical dystonia, cerebral palsy, migraines and hyperhidrosis. We tried to trace its history from its inception to its recent urological applications. Materials and Methods: Historical articles about botulinum toxin were reviewed and a Medline search was performed for its urological utility. We hereby present a brief review of historical aspects of BoNT and its applications in urology. Results: In 1793, the first known outbreak of botulism occurred due to ‘spoiled’ sausage in Wildebad, Germany. The German physician and poet Justinus Kerner published the first accurate description of the clinical symptoms of botulism (sausage poison). He was also the first to mention its potential therapeutic applications. In urology, BoNT has been used in bladder and urethral lesions with varying degree of success. Recently, BoNT applications were explained for prostatic disorders. BoNT applications in urology are in the treatment of detrusor external sphincter dyssynergia, detrusor overactivity, detrusor underactivity, spastic conditions of the urethral sphincter, chronic prostate pain, interstitial cystitis, non-fibrotic bladder outflow obstruction (including benign prostatic hyperplasia) and acute urinary retention in women. Conclusion: Justinus Kerner is the godfather of botulism research. The role of BoNT in urology has evolved exponentially and it is widely used as an adjuvant in voiding dysfunction. In the future, its utility will broaden and guide the urologist in managing various urological disorders.
A New Sickling Variant ‘Hb S-Wake β[(Glu6Val-Asn139 Ser)]’ Found in a Compound Heterozygote with Hb S β(Glu6Val) Coinherited with Homozygous α-Thalassemia-2: Phenotype and Molecular Characteristics
Authors: Kutlar F. , Redding-Lallinger R. , Meiler S.E. , Bakanay S.M. , Borders L. , Kutlar A.
Published: September 2010

We report the case of a 14-year-old African-American boy who was diagnosed with sickle cell disease. Laboratory tests showed that the patient was a compound heterozygote for a novel Hb variant with a double mutation detected on βS allele, Hb S βGlu6Val, and βAsn139Ser substitution, i.e. a β-chain variant named ‘Hb S-Wake’. The patient also carried a single Hb S mutation in trans allele, leading to Hb SS-Wake disease. He had coinherited homozygous α+-thalassemia (–α3.7/–α3.7) simultaneously which resulted in multiple globin gene abnormalities.
Trends in Stroke Attack Rates and Case Fatality in the Hunter Region, Australia 1996–2008
Authors: Marsden Dianne L. , Spratt Neil J. , Walker Rhonda , Barker Daniel , Attia John , Pollack Michael , Parsons Mark W. , Levi Christopher R.
Published: September 2010

Background: The Hunter area in New South Wales, Australia, is a well-defined geographical area with a population of 578,486 (2006). This paper presents trends from 1996 to 2008 for prospectively registered hospital admissions of adults aged 20 years and above with acute stroke. Method: Crude, age-standardised and age-specific stroke attack rates per 100,000 population and case fatality rates at standard time points were calculated. A medical record audit of stroke and stroke mimics was undertaken to determine discharge coding accuracy. Results: 9,796 acute stroke events were registered among 8,830 individuals at 14 public acute hospitals. Crude and age-standardised attack rates decreased consistently from 1996 to 2008. Crude rates fell from 184 to 176 per 100,000 population and age-standardised rates from 129 to 106 per 100,000 (attack rate reduction of 0.85% per year, p = 0.027; and 2.38% per year, p < 0.001, respectively). Annual attack rates for females were on average 27.70% (p < 0.001) lower than for males. Age-specific rates fell for each age bracket between 45 and 74 years. Case fatality rates remained constant. There was a 97.5% proportion of agreement between audit and coding. Conclusion: This study demonstrates falling stroke attack rates but stable case fatality over 13 years in a mixed urban and rural population of New South Wales, Australia. It suggests benefits from cardio- and cerebrovascular prevention strategies; however, it also indicates that stroke remains a major disease burden in this region.
Nineteen-Year Trends in Risk Factors, Clinical Characteristics and Prognosis in Lacunar Infarcts
Authors: Arboix Adrià , Massons Joan , García-Eroles Luís , Targa Cecília , Comes Emili , Parra Olga , Oliveres Montserrat
Published: September 2010

Background: Cardiovascular risk factors, clinical features and early outcome of first-ever cerebral lacunar infarcts from 1986 to 2004, using the Sagrat Cor Hospital of Barcelona Stroke Registry, were assessed and compared with data from patients with nonlacunar infarction. Methods: The study population consisted of 566 patients with lacunar infarct and 1,516 patients with nonlacunar infarct. Secular trends for the periods 1986–1992, 1993–1998 and 1999–2004 were analyzed. Results: Age and the percentage of very old patients (≧85 years old) increased significantly (p < 0.001) throughout the time period. There was a significant decrease in the percentage of patients with hypertension, but the percentage of patients with chronic obstructive pulmonary disease increased. The use of brain magnetic resonance imaging (MRI) also increased significantly. The median length of hospital stay decreased significantly. Conclusions: Significant changes over a 19-year period included an increase in the patients’ age, frequency of very old patients (≧85 years old) and use of MRI studies, whereas the frequency of hypertension and length of hospital stay decreased.
Characteristics of Body Composition and Nutritional Status in Patients Receiving Hemodialysis Therapy for More than 30 Years
Authors: Ishihara Miwa , Otsubo Shigeru , Kimata Naoki , Akiba Takashi , Nitta Kosaku
Published: September 2010

Background/Aims: We investigated the body composition and nutritional status of extremely long-term (more than 30 years) hemodialysis patients. Methods: Eighty outpatients receiving maintenance hemodialysis (including 18 for more than 30 years) were enrolled. We classified the patients according to the duration of hemodialysis therapy (less than 10 years, 10–20 years, 20–30 years, or over 30 years) and compared the laboratory and anthropometric data. Results: No significant differences in age or the total protein, albumin, total cholesterol, triglyceride or CRP levels were observed. The corrected body mass index (BMI) was significantly lower in the more than 30 years than in the less than 10 years group. The corrected arm muscle area (AMA) was significantly lower in the more than 30 years group than in the other groups. Conclusion: In extremely long-term hemodialysis outpatients, the BMI and AMA were reduced, whereas nutritional markers were relatively preserved.
Medial Medullary Infarction Identified by Diffusion-Weighted Magnetic Resonance Imaging
Authors: Shono Yuji , Koga Masatoshi , Toyoda Kazunori , Matsuoka Hideki , Yokota Chiaki , Uehara Toshiyuki , Yamamoto Haruko , Minematsu Kazuo
Published: September 2010

Objective: To elucidate the frequency and clinical profiles of patients with medial medullary infarction (MMI) identified by diffusion-weighted MRI (DWI). Methods: We assessed the frequency, radiological findings, etiology and clinical features of MMI detected by DWI from our single-center registry of acute ischemic patients. Results: Thirty patients (1.5% of 2,014 with ischemic stroke) had MMI, including isolated unilateral MMI in 26 patients. Lesions were located by DWI in the rostral medulla of 25 patients (83%). Culprit infarcts that were undetectable by DWI in 6 (38%) of 16 patients who were assessed within 24 h after onset were later confirmed as MMI. The major etiological mechanism was small artery occlusion (SAO; 19 patients) and the median initial National Institutes of Health Stroke Scale score was 4 (interquartile range: 3–4.75). The most frequent symptom was contralateral hemiparesis (27 patients). None of the patients fulfilled the classical Dejerine Triad. Twenty-two patients (73%) had a modified Rankin Scale score of ≤2 at 3 months. A patient developed transient ischemic attack within 3 months; none developed recurrent stroke. Conclusions: Rostral medullary infarction with mild neurological deficits resulting from SAO is relatively frequent. Because emergency DWI within 24 h could not detect MMI in one third of the patients, this type of infarction could be misdiagnosed as capsular/pontine lacunae or other neurological disorders.
Influence of the Discomfort Reported by Children on the Performance of Approximal Caries Detection Methods
Authors: Novaes T.F. , Matos R. , Raggio D.P. , Imparato J.C.P. , Braga M.M. , Mendes F.M.
Published: September 2010

This in vivo study aimed to evaluate the performance of methods of approximal caries detection in primary molars and to assess the influence of the discomfort caused by these methods on their performance. Two examiners evaluated 76 children (4–12 years old) using visual inspection (ICDAS), radiography and a laser fluorescence device (DIAGNOdent pen, LFpen). The reference standard was visual inspection after temporary separation with orthodontic rubbers. Surfaces were classified as sound, noncavitated (NC) or cavitated (Cav), and performance was assessed at both NC and Cav thresholds. Wong-Baker faces scale was employed to assess the discomfort. Multilevel analysis was performed to verify the influence of discomfort on performance, considering the number of false-positives and false-negatives as outcome. At NC threshold, visual inspection achieved better performance (sensitivities and accuracies around 0.67) than other methods (sensitivities around 0.25 and accuracies around 0.35). At Cav threshold, visual inspection presented lower sensitivity (0.23 and 0.19), and LFpen (0.52 and 0.42) and radiography (0.52) presented similar sensitivities. Concerning the influence of the discomfort, at NC threshold, when discomfort was present, the number of false-negative results was lower with LFpen and the number of false-positive results was higher with visual inspection. At Cav threshold, the number of false-positive results was higher with LFpen. In conclusion, radiography and LFpen achieved similar performance in detecting approximal caries lesions in primary teeth and the discomfort caused by visual inspection and LFpen can influence the performance of these methods, since a higher number of false-positive or false-negative results occurred in children who reported discomfort.
Genome-Wide Linkage and Positional Candidate Gene Study of Blood Pressure Response to Dietary Potassium Intervention
Authors: Kelly Tanika N. , Hixson James E. , Rao Dabeeru C. , Mei Hao , Rice Treva K. , Jaquish Cashell E. , Shimmin Lawrence C. , Schwander Karen , Chen Chung-Shuian , Liu Depei , Chen Jichun , Bormans Concetta , Shukla Pramila , Farhana Naveed , Stuart Colin , Whelton Paul K. , He Jiang , Gu Dongfeng
Published: September 2010

Background—

Genetic determinants of blood pressure (BP) response to potassium, or potassium sensitivity, are largely unknown. We conducted a genome-wide linkage scan and positional candidate gene analysis to identify genetic determinants of potassium sensitivity.

Methods and Results—

A total of 1906 Han Chinese participants took part in a 7-day high-sodium diet followed by a 7-day high-sodium plus potassium dietary intervention. BP measurements were obtained at baseline and after each intervention using a random-zero sphygmomanometer. Significant linkage signals (logarithm of odds [LOD] score, >3) for BP responses to potassium were detected at chromosomal regions 3q24-q26.1, 3q28, and 11q22.3-q24.3. Maximum multipoint LOD scores of 3.09 at 3q25.2 and 3.41 at 11q23.3 were observed for absolute diastolic BP (DBP) and mean arterial pressure (MAP) responses, respectively. Linkage peaks of 3.56 at 3q25.1 and 3.01 at 11q23.3 for percent DBP response and 3.22 at 3q25.2, 3.01 at 3q28, and 4.48 at 11q23.3 for percent MAP response also were identified. Angiotensin II receptor, type 1 (
AGTR1
), single-nucleotide polymorphism rs16860760 in the 3q24-q26.1 region was significantly associated with absolute and percent systolic BP responses to potassium (
P
=0.0008 and
P
=0.0006, respectively). Absolute (95% CI) systolic BP responses for genotypes C/C, C/T, and T/T were −3.71 (−4.02 to −3.40), −2.62 (−3.38 to −1.85), and 1.03 (−3.73 to 5.79) mm Hg, respectively, and percent responses (95% CI) were −3.07 (−3.33 to −2.80), −2.07 (−2.74 to −1.41), and 0.90 (−3.20 to 4.99), respectively. Similar trends were observed for DBP and MAP responses.

Conclusions—

Genetic regions on chromosomes 3 and 11 may harbor important susceptibility loci for potassium sensitivity. Furthermore, the
AGTR1
gene was a significant predictor of BP responses to potassium intake.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00721721.
Regulating Tissue Research: Do We Need Additional Rules to Protect Research Participants?
Authors: Wright Jessica , Gevers Sjef , Ploem Corrette , Śliwka Marcin
Published: September 2010

This article explores whether additional rules are needed for the regulation of tissue research in Europe. A human rights-based approach (referring to international documents and illustrative examples from national legislation) is taken to address the question: what is so special about tissue, in particular when compared to personal data? The existing regimes in Europe on data protection and clinical trials are presented and examined for their suitability to govern tissue research, taking into account the differences between data and tissue. Six recommendations are outlined, highlighting important points future legislation on tissue research must take into account.