bluuebunny/crossref_metadata_2025 huggingface dataset:
Context-based search for 3D models
Authors: Fisher Matthew , Hanrahan Pat
Published: December 2010

Large corpora of 3D models, such as Google 3D Warehouse, are now becoming available on the web. It is possible to search these databases using a keyword search. This makes it possible for designers to easily include existing content into new scenes. In this paper, we describe a method for context-based search of 3D scenes. We first downloaded a large set of scene graphs from Google 3D Warehouse. These scene graphs were segmented into individual objects. We also extracted tags from the names of the models. Given the object shape, tags, and spatial relationship between pairs of objects, we can predict the strength of a relationship between a candidate model and an existing object in the scene. Using this function, we can perform context-based queries. The user specifies a region in the scene they are modeling using a 3D bounding box, and the system returns a list of related objects. We show that context-based queries perform better than keyword queries alone, and that without any keywords our algorithm still returns a relevant set of models.
Style-content separation by anisotropic part scales
Authors: Xu Kai , Li Honghua , Zhang Hao , Cohen-Or Daniel , Xiong Yueshan , Cheng Zhi-Quan
Published: December 2010

We perform co-analysis of a set of man-made 3D objects to allow the creation of novel instances derived from the set. We analyze the objects at the part level and treat the
anisotropic part scales
as a shape style. The co-analysis then allows
style transfer
to synthesize new objects. The key to co-analysis is part correspondence, where a major challenge is the handling of large style variations and diverse geometric content in the shape set. We propose
style-content separation
as a means to address this challenge. Specifically, we define a
correspondence-free
style signature for style clustering. We show that confining analysis to within a style cluster facilitates tasks such as co-segmentation, content classification, and deformation-driven part correspondence. With part correspondence between each pair of shapes in the set, style transfer can be easily performed. We demonstrate our analysis and synthesis results on several sets of man-made objects with style and content variations.
Multi-feature matching of fresco fragments
Authors: Toler-Franklin Corey , Brown Benedict , Weyrich Tim , Funkhouser Thomas , Rusinkiewicz Szymon
Published: December 2010

We present a multiple-feature approach for determining matches between small fragments of archaeological artifacts such as Bronze-Age and Roman frescoes. In contrast with traditional 2D and 3D shape matching approaches, we introduce a set of feature descriptors that are based on not only color and shape, but also
normal maps.
These are easy to acquire and combine high data quality with discriminability and robustness to some types of deterioration. Our feature descriptors range from general-purpose to domain-specific, and are quick to compute and match. We have tested our system on three datasets of fresco fragments, demonstrating that multi-cue matching using different subsets of features leads to different tradeoffs between efficiency and effectiveness. In particular, we show that normal-based features are more effective than color-based ones at similar computational complexity, and that 3D features are more discriminative than ones based on 2D or normals, but at higher computational cost. We also demonstrate how machine learning techniques can be used to effectively combine our new features with traditional ones. Our results show good retrieval performance, significantly improving upon the match prediction rate of state-of-the-art 3D matching algorithms, and are expected to extend to general matching problems in applications such as texture synthesis and forensics.
VSkyline
Authors: Cho Sung-Ryoung , Lee Jongwuk , Hwang Seung-Won , Han Hwansoo , Lee Sang-Won
Published: December 2010

A dominance test, which decides the dominance relationship between tuples, is a core operation in skyline computation. Optimizing dominance tests can thus improve the performance of all existing skyline algorithms. Towards this goal, this paper proposes a vectorization of dominance tests in SIMD architectures. Specifically, our vectorization can perform the dominance test of multiple consecutive dimensions in parallel, thereby achieving a speedup of SIMD parallelism degree in theory. However, achieving such performance gain is non-trivial due to complex control dependencies within the dominance test. To address this problem, we devise an efficient vectorization, called VSkyline, which performs the dominance test with SIMD instructions by determining incomparability in a block of four dimensional values. Experimental results using a performance monitor show that VSkyline considerably reduces the numbers of both executed instructions and branch mispredictions.
Business intelligence for small and middle-sized entreprises
Authors: Grabova Oksana , Darmont Jerome , Chauchat Jean-Hugues , Zolotaryova Iryna
Published: December 2010

Data warehouses are the core of decision support systems, which nowadays are used by all kind of enterprises in the entire world. Although many studies have been conducted on the need of decision support systems (DSSs) for small businesses, most of them adopt existing solutions and approaches, which are appropriate for large-scaled enterprises, but are inadequate for small and middle-sized enterprises.

Small enterprises require cheap, lightweight architectures and tools (hardware and software) providing online data analysis. In order to ensure these features, we review web-based business intelligence approaches. For real-time analysis, the traditional OLAP architecture is cumbersome and storage-costly; therefore, we also review in-memory processing.

Consequently, this paper discusses the existing approaches and tools working in main memory and/or with web interfaces (including freeware tools), relevant for small and middle-sized enterprises in decision making.
The SIGMOD 2010 programming contest a distributed query engine
Authors: Genzmer Clément , Hudlet Volker , Park Hyunjung , Schall Daniel , Senellart Pierre
Published: December 2010

We report on the second annual ACM SIGMOD programming contest, which consisted in building an efficient distributed query engine on top of an in-memory index. This article is co-authored by the organizers of the competition (Clément Genzmer, Pierre Senellart) and the students who built the two leading implementations (Volker Hudlet, Hyunjung Park, Daniel Schall).
Metabolic pathways promoting intrahepatic fatty acid accumulation in methionine and choline deficiency: implications for the pathogenesis of steatohepatitis
Authors: Macfarlane David P. , Zou Xiantong , Andrew Ruth , Morton Nicholas M. , Livingstone Dawn E. W. , Aucott Rebecca L. , Nyirenda Moffat J. , Iredale John P. , Walker Brian R.
Published: December 2010

The pathological mechanisms that distinguish simple steatosis from steatohepatitis (or NASH, with consequent risk of cirrhosis and hepatocellular cancer) remain incompletely defined. Whereas both a methionine- and choline-deficient diet (MCDD) and a choline-deficient diet (CDD) lead to hepatic triglyceride accumulation, MCDD alone is associated with hepatic insulin resistance and inflammation (steatohepatitis). We used metabolic tracer techniques, including stable isotope ([13C4]palmitate) dilution and mass isotopomer distribution analysis (MIDA) of [13C2]acetate, to define differences in intrahepatic fatty acid metabolism that could explain the contrasting effect of MCDD and CDD on NASH in C57Bl6 mice. Compared with control-supplemented (CS) diet, liver triglyceride pool sizes were similarly elevated in CDD and MCDD groups (24.37 ± 2.4, 45.94 ± 3.9, and 43.30 ± 3.5 μmol/liver for CS, CDD, and MCDD, respectively), but intrahepatic neutrophil infiltration and plasma alanine aminotransferase (31 ± 3, 48 ± 4, 231 ± 79 U/l, P < 0.05) were elevated only in MCDD mice. However, despite loss of peripheral fat in MCDD mice, neither the rate of appearance of palmitate (27.2 ± 3.5, 26.3 ± 2.3, and 28.3 ± 3.5 μmol·kg−1·min−1) nor the contribution of circulating fatty acids to the liver triglyceride pool differed between groups. Unlike CDD, MCDD had a defect in hepatic triglyceride export that was confirmed using intravenous tyloxapol (142 ± 21, 122 ± 15, and 80 ± 7 mg·kg−1·h−1, P < 0.05). Moreover, hepatic de novo lipogenesis was significantly elevated in the MCDD group only (1.4 ± 0.3, 2.3 ± 0.4, and 3.4 ± 0.4 μmol/day, P < 0.01). These findings suggest that important alterations in hepatic fatty acid metabolism may promote the development of steatohepatitis. Similar mechanisms may predispose to hepatocyte damage in human NASH.
Importance of Lipopolysaccharide and Cyclicβ-1,2-Glucans inBrucella-Mammalian Infections
Authors: Haag Andreas F. , Myka Kamila K. , Arnold Markus F. F. , Caro-Hernández Paola , Ferguson Gail P.
Published: December 2010

Brucellaspecies are the causative agents of one of the most prevalent zoonotic diseases: brucellosis. Infections byBrucellaspecies cause major economic losses in agriculture, leading to abortions in infected animals and resulting in a severe, although rarely lethal, debilitating disease in humans.Brucellaspecies persist as intracellular pathogens that manage to effectively evade recognition by the host's immune system. Sugar-modified components in theBrucellacell envelope play an important role in their host interaction.Brucellalipopolysaccharide (LPS), unlikeEscherichia coliLPS, does not trigger the host's innate immune system.Brucellaproduces cyclicβ-1,2-glucans, which are important for targeting them to their replicative niche in the endoplasmic reticulum within the host cell. This paper will focus on the role of LPS and cyclicβ-1,2-glucans inBrucella-mammalian infections and discuss the use of mutants, within the biosynthesis pathway of these cell envelope structures, in vaccine development.
Rituximab Administration and Reactivation of HBV
Authors: Tsutsumi Yutaka , Ogasawara Reiki , Kamihara Yusuke , Ito Shinichi , Yamamoto Yoshiya , Tanaka Junji , Asaka Masahiro , Imamura Masahiro
Published: December 2010

Rituximab is a drug used for the treatment of B-cell non-Hodgkin's lymphoma, and its range of use has expanded to the treatment of collagen diseases such as idiopathic thrombocytopenic purpura and rheumatoid arthritis. One serious complication of rituximab use is the reactivation of dormant hepatitis B virus, and prevention of this phenomenon has become an urgent issue. This paper provides a general outline of the problem through an analysis of patient cases that we and other groups have experienced to date.
Combined Acquisition and Tracking Methods for GPS L1 C/A and L1C Signals
Authors: Macchi-Gernot Florence , Petovello Mark G. , Lachapelle Gérard
Published: December 2010

As part of the GPS modernization, the GPS L1 C/A signal will be augmented by the L1C signal. With this improvement, for the first time, several signals from the same constellation will be available at the same frequency. In this paper, an acquisition method is implemented to combine the GPS L1 C/A and L1C signals before correlation. The combined acquisition succeeds to acquire the signal at low C/N0, whereas the acquisition of the L1C data channel alone fails. Concerning the tracking, a method to combine the GPS L1 C/A and L1C signals before the discriminator is developed. This method shows better performance than the traditional tracking using only one signal. Finally, a Kalman filter to combine the signals in the tracking is developed. It shows better performance than the traditional tracking in all conditions. Since the L1C signal will not be broadcast before 2013, these methods are tested using a software signal simulator.
Fixed Points and Stability in Nonlinear Equations with Variable Delays
Authors: Ding Liming , Li Xiang , Li Zhixiang
Published: December 2010

We consider two nonlinear scalar delay differential equations with variable delays and give some new conditions for the boundedness and stability by means of the contraction mapping principle. We obtain the differences of the two equations about the stability of the zero solution. Previous results are improved and generalized. An example is given to illustrate our theory.
Comorbidity-Adjusted Survival in Early Stage Lung Cancer Patients Treated with Hypofractionated Proton Therapy
Authors: Do Sharon Y. , Bush David A. , Slater Jerry D.
Published: December 2010

Objective. To determine the influence of comorbidity on survival in early-stage lung cancer patients treated with proton radiotherapy, using the Charlson Comorbidity Index.Study Design and Setting. Fifty-four non-small-cell lung cancer patients, treated prospectively in a phase II clinical trial with hypofractionated proton therapy, were analyzed retrospectively to assess their burden of comorbid disease as expressed by Charlson Comorbidity Index. Using the Charlson Comorbidity Index method, a predicted survival curve based on comorbidity was formulated and compared to the observed mortality from causes other than lung cancer in the study population.Results. The study population had an average age score of 2.8 and an average Charlson Comorbidity Index of 4.7. Predicted survival was calculated to be 67% and 50% at 2 and 4 years, respectively. Actual comorbidity-specific survival at 2 and 4 years was 64% and 45%, respectively. The observed survival fell within the 95% confidence intervals of the predicted survival at all time points up to 5 years.Conclusion. Predicted mortality from concurrent disease, based on Charlson Comorbidity Index, correlated well with observed comorbidity-specific mortality. This helps substantiate the accuracy of the data coding in cause of death and strengthens previously reported disease-specific survival rates.
Pseudomembranous Trigonitis: A Common but Underrecognized Urological Entity
Authors: Stavropoulos M. , Papatsoris A. G. , Konstantinidis C. , Chrisofos M.
Published: December 2010

Pseudomembranous trigonitis is the term used to describe squamous metaplastic changes of the bladder trigone, which affect nearly 40% of adult females. We present the characteristics of this underrecognized clinical entity and encourage further relevant research.
Serial Assessment of Cardiac Function during and following Mitoxantrone Infusion in 30 Consecutive Patients with Multiple Sclerosis
Authors: Franzen Damian , Haus Angelika , Hellmich Martin
Published: December 2010

Immunosuppressive therapy is an established therapeutic option in patients suffering from multiple sclerosis (MS). In an open nonrandomized study we serially assessed cardiac function in 30 consecutive patients with MS before, during, and after mitoxantrone therapy. Mitoxantrone (12 mg/m2) was administered intravenously at 3-month intervals. Before each infusion, cardiac function was assessed by history taking, resting electrocardiogram, and echocardiography. Whereas no patient experienced clinical signs of heart failure, left ventricular pump function decreased continuously during mitoxantrone therapy and did not recover after cessation. The presented data suggest a dose-dependent and long-lasting toxic cardiac effect of low-dose mitoxantrone therapy in MS.
Polymer-Based Self-Standing Flexible Strain Sensor
Authors: Martinez Fernando , Obieta Gregorio , Uribe Ion , Sikora Tomasz , Ochoteco Estibalitz
Published: December 2010

The design and characterization of polymer-based self-standing flexible strain sensors are presented in this work. Properties as lightness and flexibility make them suitable for the measurement of strain in applications related with wearable electronics such as robotics or rehabilitation devices. Several sensors have been fabricated to analyze the influence of size and electrical conductivity on their behavior. Elongation and applied charge were precisely controlled in order to measure different parameters as electrical resistance, gauge factor (GF), hysteresis, and repeatability. The results clearly show the influence of size and electrical conductivity on the gauge factor, but it is also important to point out the necessity of controlling the hysteresis and repeatability of the response for precision-demanding applications.
A Study on the Relationship between Connecting Different Types of Nodes and Disassortativity by Degree
Authors: Dong Chengdong
Published: December 2010

This paper investigates how to change the disassortativity of the whole network by connecting nodes of different types in two communities. A model connecting two multi‐center networks is studied to see if analytical results are achievable. There are three main methods to connect two multi‐center subnetworks depending on whether the connecting nodes are centers: (1) connect the centers of one sub‐network to noncenter nodes of the other sub‐network, (2) connect the centers of the two sub‐networks together, and (3) connect non‐center nodes of the two sub‐networks. The results show that the disassortative property of a single multicenter network can be maintained in scenarios (1) and (2) above, but the disassortativity is changed in (3). In conclusion, either assortativity or disassortativity is achievable by connecting nodes with different degree properties in an ideal network constructed from two communities with similar network topology.
Fiber Optic Broadband Ultrasonic Probe for Virtual Biopsy: Technological Solutions
Authors: Biagi E. , Cerbai S. , Masotti L. , Belsito L. , Roncaglia A. , Masetti G. , Speciale N.
Published: December 2010

An ultrasonic probe was developed by using, in conjunction, optoacoustic and acousto-optic devices based on fiber optic technology. The intrinsic high frequency and wide bandwidth associated both to the opto-acoustic source and to the acousto-optic receiving element could open a way towards a “virtual biopsy” of biological tissue. A Micro-Opto-Mechanical-System (MOMS) approach is proposed to realize the broadband ultrasonic probe on micromachined silicon frames suited to be mounted on the tip of optical fibers.
Complete Triaxis Magnetometer Calibration in the Magnetic Domain
Authors: Renaudin Valérie , Afzal Muhammad Haris , Lachapelle Gérard
Published: December 2010

This paper presents an algorithm for calibrating erroneous tri-axis magnetometers in the magnetic field domain. Unlike existing algorithms, no simplification is made on the nature of errors to ease the estimation. A complete error model, including instrumentation errors (scale factors, nonorthogonality, and offsets) and magnetic deviations (soft and hard iron) on the host platform, is elaborated. An adaptive least squares estimator provides a consistent solution to the ellipsoid fitting problem and the magnetometer's calibration parameters are derived. The calibration is experimentally assessed with two artificial magnetic perturbations introduced close to the sensor on the host platform and without additional perturbation. In all configurations, the algorithm successfully converges to a good estimate of the said errors. Comparing the magnetically derived headings with a GNSS/INS reference, the results show a major improvement in terms of heading accuracy after the calibration.
An Unusual Case of Aplastic Anemia Caused by Temozolomide
Authors: Comez Gazi , Sevinc Alper , Sever Ozlem Nuray , Babacan Taner , Sarı Ibrahim , Camci Celalettin
Published: December 2010

Radiotherapy and concomitant/adjuvant therapy with temozolomide are a common treatment regimen for children and adults with high-grade glioma. Although temozolomide is generally safe, it can rarely cause life-threatening complications. Here we report a case of a 31-year-old female patient who underwent surgical resection followed by radiotherapy plus concomitant temozolomide. She developed pancytopenia after adjuvant treatment with temozolomide. A bone marrow aspiration and biopsy showed hypocellularity with very few erythroid and myeloid cells, consistent with aplastic anemia. In the English literature, aplastic anemia due to temozolomide is extremely rare.
Effect of Source, Surfactant, and Deposition Process on Electronic Properties of Nanotube Arrays
Authors: Jain Dheeraj , Rouhi Nima , Rutherglen Christopher , Densmore Crystal G. , Doorn Stephen K. , Burke Peter J.
Published: December 2010

The electronic properties of arrays of carbon nanotubes from several different sources differing in the manufacturing process used with a variety of average properties such as length, diameter, and chirality are studied. We used several common surfactants to disperse each of these nanotubes and then deposited them on Si wafers from their aqueous solutions using dielectrophoresis. Transport measurements were performed to compare and determine the effect of different surfactants, deposition processes, and synthesis processes on nanotubes synthesized using CVD, CoMoCAT, laser ablation, and HiPCO.
Successful Treatment of Chronic Mucocutaneous Candidiasis Caused by Azole-ResistantCandida albicanswith Posaconazole
Authors: Firinu Davide , Massidda Orietta , Lorrai Maria Maddalena , Serusi Loredana , Peralta Monica , Barca Maria Pina , Serra Paolo , Manconi Paolo Emilio
Published: December 2010

Refractory or recurrent infections of skin, nails, and the mucous membranes are clinical signs of chronic mucocutaneous candidiasis, frequently associated with immunological defects. Here we describe a 39-years-old female patient, with familial CMC, that presented with an extensive infection caused by an azole-resistantCandida albicansisolate, successfully treated with posaconazole.
Neuron Regeneration and Proliferation Effects of Danshen and Tanshinone IIA
Authors: Shen Jui-Lung , Chen Yueh-Sheng , Lin Jing-Ying , Tien Yun-Chen , Peng Wen-Huang , Kuo Chia-Hua , Tzang Bor-Show , Wang Hwai-Lee , Tsai Fuu-Jen , Chou Ming-Chih , Huang Chih-Yang , Lin Chien-Chung
Published: December 2010

This study evaluates the proliferative effects of danshen and its monomer extract, tanshinone IIA, on Schwann cell proliferation. A piece of silicone rubber was guided across a 15‐mm gap in the sciatic nerve of a rat. This nerve gap was then filled with different concentrations of danshen (0–100 mg/mL). The results showed that danshen increased the expressions of uPA, cyclin D1, E and ERK, JNK, and P38 MAP kinases via the FGF‐2 signaling pathway in a dose‐dependent manner. RSC96, Schwann cells were also administered with danshen (0, 20, 40, 60, 80, and 100 μg/mL) and tanshinone IIA (0, 2, 4, 6, 8, and 10 μg/mL). In lower concentrations,
danshen and tanshinone IIA exhibited an apparent effect on Schwann cells. Similar effects were also demonstrated in the FGF‐2‐uPA regulating cascade and cell cycle proliferative protein results. Schwann cell migration was elevated as well. We used MAPK‐signaling chemical inhibitors and identified the proliferative effects of danshen and tanshinone IIA as MAPK‐signaling dependent.
The results from the in vitro systems indicate that danshen and tanshinone IIA can be used to induce Schwann cell proliferation,
and in vivo results potentially suggest that danshen and tanshinone IIA might enhance neuron regeneration.
Basal Cell Carcinoma: 10 Years of Experience
Authors: Cigna Emanuele , Tarallo Mauro , Maruccia Michele , Sorvillo Valentina , Pollastrini Alessia , Scuderi Nicolò
Published: December 2010

Introduction. Basal cell carcinoma (BCC) is a locally invasive malignant epidermal tumour. Incidence is increasing by 10% per year; incidence of metastases is minimal, but relapses are frequent (40%–50%). The complete excision of the BCC allows reduction of relapse.Materials and Methods. The study cohort consists of 1123 patients underwent surgery for basal cell carcinoma between 1999 and 2009. Patient and tumor characteristics recorded are: age; gender; localization (head and neck, trunk, and upper and lower extremities), tumor size, excisional margins adopted, and relapses.Results. The study considered a group of 1123 patients affected by basal cell carcinoma. Relapses occurred in 30 cases (2,67%), 27 out of 30 relapses occurred in noble areas, where peripheral margin was <3 mm. Incompletely excised basal cell carcinoma occurred in 21 patients (1,87%) and were treated with an additional excision.Discussion. Although guidelines indicate 3 mm peripheral margin of excision in BCC <2 cm, in our experience, a margin of less than 5 mm results in a high risk of incomplete excisions.
Growth of Human Colorectal Cancer SW1116 Cells Is Inhibited by Cytokine-Induced Killer Cells
Authors: Wang Yao , Dai Hanren , Li Hong , Lv Haiyan , Wang Tao , Fu Xiaobing , Han Weidong
Published: December 2010

Previous reports have suggested that treatment with cytokine-induced killer (CIK) cells may benefit patients with various types of tumor. The aim of this study was to evaluate the antitumor effects of CIK cells against the colorectal cancer line SW1116in vitroandin vivo. CIK cells were generated routinely from peripheral blood mononuclear cells of healthy human donors, and the number of CD3+CD56+cells was expanded more than 1300-fold after 14-day culture. At an effector : target cell ratio of 50 : 1, the percentage lysis of SW1116 cells reached 68% in the presence of CIK cells, Experimental mice injected with SW1116 cells subcutaneously were divided randomly into four groups: untreated, 5-fluorouracil (5-FU)-treated, CIK-consecutive treated (injected once/day) and CIK-interval treated (injected once every 5 days). CIK cells were injected abdominally five times in total. Compared with the untreated group, xenograft growth was inhibited greatly by CIK treatment, to nearly the same extent as with 5-FU treatment. We demonstrated that the necrotic area in the tumor xenograft was markedly larger in the CIK-treated groups than in the other groups. These findings suggest that CIK-based immunotherapy may represent an effective choice for patients with colorectal cancer.
Zataria multiflora Boiss and Carvacrol Affect β2‐Adrenoceptors of Guinea Pig Trachea
Authors: Boskabady Mohammad Hossein , Kaveh Mahsa , Eftekhar Naeima , Nemati Ali
Published: December 2010

The stimulatory effect of Zataria multiflora Boiss (Labiatae) and carvacrol on β‐adrenoceptors was examined on guinea pig trachea. The effects of three concentrations of aqueous‐ethanolic extract, carvacrol, and propranolol (β‐receptor antagonist) on β‐adrenoceptors were tested in nonincubated (group 1, n = 8) and incubated tracheal chains with 1 μM chlorpheniramine (histamine H1 receptor antagonist) (group 2, n = 5). Isoprenaline (β‐receptor agonist) curves obtained in the presence of all concentrations of the extract and carvacrol showed leftward shifts compared with that of saline in both groups. In both groups, the EC50 (the effective concentration of isoprenaline, causing 50% of maximum response) obtained in the presence of all concentrations of the extract and carvacrol was significantly lower compared to that of saline (P < .01 to P < .001). All values of (CR‐1: (EC50 in the presence of active substances/EC50 obtained in the presence of saline)‐1) obtained in the presence of concentrations of the extract and carvacrol in both groups were negative and significantly different from that of propranolol (P < .001 for all cases). The results indicated a stimulatory effect of Zataria multiflora Boiss extract on β2‐adrenoceptors which is perhaps due to its constituent, carvacrol.
Current Therapeutic Approaches in Metastatic and Recurrent Ewing Sarcoma
Authors: Huang Michael , Lucas Kenneth
Published: December 2010

Ewing sarcoma (ES) is the second most common type of primary bone malignancy in children and young adults. Survival rates for localized ES have improved to upwards of 70% with aggressive chemotherapy and local control. On the other hand, there has been little improvement in survival rates for patients with metastatic or recurrent ES. Herein we review the different current therapeutic approaches available, including the different upfront and salvage chemotherapy regimens, the role for stem cell transplantation, and potential use of immunotherapy.
Aldehyde Dehydrogenase Activity Selects for Lung Adenocarcinoma Stem Cells Dependent on Notch Signaling
Authors: Sullivan James P. , Spinola Monica , Dodge Michael , Raso Maria G. , Behrens Carmen , Gao Boning , Schuster Katja , Shao Chunli , Larsen Jill E. , Sullivan Laura A. , Honorio Sofia , Xie Yang , Scaglioni Pier P. , DiMaio J. Michael , Gazdar Adi F. , Shay Jerry W. , Wistuba Ignacio I. , Minna John D.
Published: December 2010

Aldehyde dehydrogenase (ALDH) is a candidate marker for lung cancer cells with stem cell-like properties. Immunohistochemical staining of a large panel of primary non–small cell lung cancer (NSCLC) samples for ALDH1A1, ALDH3A1, and CD133 revealed a significant correlation between ALDH1A1 (but not ALDH3A1 or CD133) expression and poor prognosis in patients including those with stage I and N0 disease. Flow cytometric analysis of a panel of lung cancer cell lines and patient tumors revealed that most NSCLCs contain a subpopulation of cells with elevated ALDH activity, and that this activity is associated with ALDH1A1 expression. Isolated ALDH+ lung cancer cells were observed to be highly tumorigenic and clonogenic as well as capable of self-renewal compared with their ALDH− counterparts. Expression analysis of sorted cells revealed elevated Notch pathway transcript expression in ALDH+ cells. Suppression of the Notch pathway by treatment with either a γ-secretase inhibitor or stable expression of shRNA against NOTCH3 resulted in a significant decrease in ALDH+ lung cancer cells, commensurate with a reduction in tumor cell proliferation and clonogenicity. Taken together, these findings indicate that ALDH selects for a subpopulation of self-renewing NSCLC stem-like cells with increased tumorigenic potential, that NSCLCs harboring tumor cells with ALDH1A1 expression have inferior prognosis, and that ALDH1A1 and CD133 identify different tumor subpopulations. Therapeutic targeting of the Notch pathway reduces this ALDH+ component, implicating Notch signaling in lung cancer stem cell maintenance. Cancer Res; 70(23); 9937–48. ©2010 AACR.
Antitumor Activity of Pyridocarbazole and Benzopyridoindole Derivatives that Inhibit Protein Kinase CK2
Authors: Prudent Renaud , Moucadel Virginie , Nguyen Chi-Hung , Barette Caroline , Schmidt Frédéric , Florent Jean-Claude , Lafanechère Laurence , Sautel Céline F , Duchemin-Pelletier Eve , Spreux Elodie , Filhol Odile , Reiser Jean-Baptiste , Cochet Claude
Published: December 2010

The alkyloid compound ellipticine derived from the berrywood tree is a topoisomerase II poison that is used in ovarian and breast cancer treatment. In this study, we report the identification of ellipticine derivatives and their tetracyclic angular benzopyridoindole analogues as novel ATP-competitive inhibitors of the protein kinase CK2. In vitro and in vivo assays showed that these compounds have a good pharmacologic profile, causing a marked inhibition of CK2 activity associated with cell cycle arrest and apoptosis in human cancer cells. Further, in vivo assays demonstrate antitumor activity in a mouse xenograft model of human glioblastoma. Finally, crystal structures of CK2–inhibitor complex provide structural insights on the molecular basis of CK2 inhibition. Our work lays the foundation for development of clinically useful CK2 inhibitors derived from a well-studied scaffold with suitable pharmacokinetics parameters. Cancer Res; 70(23); 9865–74. ©2010 AACR.
Novel Metastasis-Related Gene CIM Functions in the Regulation of Multiple Cellular Stress–Response Pathways
Authors: Yanagisawa Kiyoshi , Konishi Hiroyuki , Arima Chinatsu , Tomida Shuta , Takeuchi Toshiyuki , Shimada Yukako , Yatabe Yasushi , Mitsudomi Tetsuya , Osada Hirotaka , Takahashi Takashi
Published: December 2010

Various stresses of the tumor microenvironment produced by insufficient nutrients, pH, and oxygen can contribute to the generation of altered metabolic and proliferative states that promote the survival of metastatic cells. Among many cellular stress–response pathways activated under such conditions are the hypoxia-inducible factor (HIF) pathway and the unfolded protein response (UPR), which is elicited as a response to endoplasmic reticulum (ER) stress. In this study, we report the identification of a novel cancer invasion and metastasis-related gene (hereafter referred to as CIM, also called ERLEC1), which influences both of these stress–response pathways to promote metastasis. CIM was identified by comparing the gene expression profile of a highly metastatic human lung cancer cell line with its weakly metastatic parental clone. We showed that CIM is critical for metastatic properties in this system. Proteomic approaches combined with bioinformatic analyses revealed that CIM has multifaceted roles in controlling the response to hypoxia and ER stress. Specifically, CIM sequestered OS-9 from the HIF-1α complex and PHD2, permitting HIF-1α accumulation by preventing its degradation. Ectopic expression of CIM in lung cancer cells increased their tolerance to hypoxia. CIM also modulated UPR through interaction with the key ER stress protein BiP, influencing cell proliferation under ER stress conditions. Our findings shed light on how tolerance to multiple cellular stresses at a metastatic site can be evoked by an integrated mechanism involving CIM, which can function to coordinate those responses in a manner that promotes metastatic cell survival. Cancer Res; 70(23); 9949–58. ©2010 AACR.
Failure of Downregulation of Survivin Following Neoadjuvant Radiochemotherapy in Rectal Cancer Is Associated with Distant Metastases and Shortened Survival
Authors: Sprenger Thilo , Rödel Franz , Beissbarth Tim , Conradi Lena-Christin , Rothe Hilka , Homayounfar Kia , Wolff Hendrik A. , Ghadimi B. Michael , Yildirim Müjdat , Becker Heinz , Rödel Claus , Liersch Torsten
Published: December 2010

Purpose: Valid molecular markers need to be implemented in clinical trials to fulfill the demand of a risk-adapted and more individualized multimodal therapy of locally advanced primary rectal cancer. In this study, the expression of the inhibitor-of-apoptosis (IAP) protein survivin was evaluated in pretreatment biopsies and corresponding posttreatment resection specimens, and was correlated to histo-pathological tumor characteristics and clinical follow-up.

Patients and Methods: One hundred sixteen patients with stage II/III rectal cancer treated with 5-FU–based neoadjuvant radiochemotherapy (RCT) at a single university medical centre within the German Rectal Cancer Trials were investigated. Survivin expression in pretreatment biopsies and surgical resection specimens were determined by immunohistochemistry by two independent institutions and correlated with histopathologic parameters, tumor recurrences, disease-free (DFS), and overall cancer-specific survival (CSS).

Results: In pretreatment biopsies, a higher survivin expression correlated with advanced ypT (P = 0.026) and ypUICC (P = 0.05) stage as well as DFS (P = 0.038) after preoperative RCT. High posttreatment survivin levels were associated with advanced ypT stage (P = 0.03) and residual lymph node metastases (P = 0.04). Moreover, neoadjuvant RCT resulted in a significant downregulation of survivin expression (P < 0.0001). A failure of RCT-induced downregulation was associated with development of distant metastases (P = 0.0056) and cancer-related death (P = 0.026), and correlated significantly with DFS (P = 0.011*/0.02**) and CSS (P = 0.0017*/0.01**) in uni-* and multivariate** analyses.

Conclusions: Survivin expression displays a marker with prognostic utility in rectal cancers. These results underline the potential of survivin to monitor individual response to RCT and encourage anti-survivin strategies in multimodal rectal cancer therapy within future randomized clinical trials. Clin Cancer Res; 17(6); 1623–31. ©2010 AACR.
Base molecular de la fenilcetonuria: Del genotipo al tratamiento clínico
Authors: Zschocke Johannes
Published: December 2010

En la era de la detección sistemática neonatal y el tratamiento presintomático de individuos con fenilcetonuria, la definición de la enfermedad ha variado desde una serie de síntomas clínicos observados en pacientes no tratados, hasta una predisposición hereditaria necesitada de una intervención alimentaria para evitar el daño cerebral y el deterioro intelectual. En consecuencia, el análisis de correlaciones entre genotipo y fenotipo debe dirigirse a la necesidad y las modalidades del tratamiento preventivo. En la fenilcetonuria, el análisis de mutaciones no es una condición indispensable para el diagnóstico y el tratamiento correctos, incluyendo el tratamiento con el cofactor tetrahidrobiopterina (BH4). Sin embargo, el impacto funcional de las mutaciones individuales ha sido investigado extensamente durante los últimos años y se dispone de correlaciones bien estudiadas entre el genotipo y varios aspectos fenotípicos. El conocimiento y la comprensión del genotipo en una fase muy temprana permiten a menudo establecer un pronóstico de la gravedad de la deficiencia de la fenilalanina hidroxilasa y proporcionar un cuadro más evidente de las características patológicas en el paciente individual. Esto puede ayudar en el tratamiento clínico. La identificación del estado de homocigosis o de heterocigosis compuesta para mutaciones nulas, indica que el paciente en cuestión no se beneficiará del tratamiento con BH4, mientras que la identificación de una mutación bien conocida, sensible a BH4, en un paciente que se había clasificado como no reactivo en una prueba de BH4, sería una indicación para reevaluar la clasificación y, en caso necesario, repetir la prueba. Deben adoptarse cuidados para reconocer errores potenciales en los resultados de los estudios moleculares y para interpretarlos en relación con los datos clínicos y bioquímicos del individuo.
Tratamiento nutricional de la fenilcetonuria
Authors: MacLeod Erin L. , Ney Denise M.
Published: December 2010

La fenilcetonuria (FCU) está causada por la actividad deficiente de la enzima fenilalanina hidroxilasa, necesaria para convertir el aminoácido (AA) esencial fenilalanina (phe) en tirosina. Con objeto de prevenir el daño neurológico es necesaria la adhesión permanente a una dieta pobre en phe, que restringe los alimentos naturales y requiere la ingestión de una fórmula de AA libre de phe para satisfacer las necesidades proteínicas. El objetivo del tratamiento nutricional de los pacientes con FCU reside en mantener concentraciones plasmáticas de phe capaces de sustentar un crecimiento, desarrollo y función mental óptimos al mismo tiempo que aporta una dieta nutricionalmente completa. En este trabajo se revisa el desarrollo de una prescripción alimentaria vitalicia para los pacientes con FCU, los resultados del tratamiento nutricional, el cumplimiento con la dieta pobre en phe durante todo el ciclo vital y nuevas opciones de terapéutica nutricional. Para satisfacer las necesidades de nutrientes se precisa una prescripción dietética individualizada, y se monitoriza la idoneidad de la ingestión de phe mediante la evaluación de sus niveles hemáticos. La elevación de las concentraciones de phe puede aparecer debido a enfermedad, ingestión excesiva o insuficiente de phe o ingestión insuficiente de la fórmula de AA. Aunque con la adhesión a la dieta pobre en phe, el crecimiento y el desarrollo son normales, es importante monitorizar el estado de las vitaminas, los minerales y los ácidos grasos esenciales, especialmente en aquellas personas que no consumen cantidades suficientes de fórmula de AA. Teniendo en cuenta la creciente población de adultos con FCU, se precisa una investigación ulterior para conocer los riesgos de aparición de osteoporosis y enfermedad cardiovascular. Existen nuevas opciones prometedoras para liberalizar la dieta y mejorar el control metabólico, como el tratamiento con tetrahidrobiopterina o el aporte complementario de AA neutros de gran tamaño. Por otra parte, los alimentos compuestos de glucomacropéptido, una proteína intacta que contiene una cantidad mínima de phe, mejoran la dieta de FCU, ofreciendo una alternativa sabrosa a la fórmula de AA. En suma, se precisan esfuerzos continuados para superar el enorme problema que conlleva la vida con FCU: la adhesión vitalicia a la dieta pobre en phe.
Nuevos enfoques del tratamiento de la fenilcetonuria
Authors: Eavri Ronen , Lorberboum-Galski Haya
Published: December 2010

Desde su descubrimiento por Følling en 1934, la fenilcetonuria (FCU) ha sido objeto de numerosos estudios de investigación, abarcando varias disciplinas como genética humana, bioquímica, desarrollo, neurobiología y otras. Durante los últimos 75 años se han mapeado diferentes mutaciones en los genes responsables de la enfermedad, se ha aclarado su base bioquímica y se han revelado los mecanismos conducentes al desenlace clínico. Por otra parte, los programas de detección sistemática de recién nacidos, basados en la prueba de Guthrie, y los análisis bioquímicos subsiguientes en niños recién nacidos, además de la dieta pobre en proteína, han ejercido un enorme impacto sobre el modo de considerar en esta época moderna los errores congénitos hereditarios del metabolismo. De hecho, este tratamiento de la FCU, simple aunque de máxima eficacia, la dieta pobre en proteína, se considera un avance notable en el tratamiento de la enfermedad al permitir la retención de niveles bajos de fenilalanina en la sangre, evitando que niveles de fenilalanina elevados y persistentes dañen el desarrollo normal del cerebro. No obstante, a pesar de la sencillez y la gran eficacia del tratamiento dietético pobre en proteína, la falta de cumplimiento de algunos pacientes afectados de FCU y sus consecuencias han alentado a los científicos a buscar constantemente métodos terapéuticos nuevos y alternativos. En esta revisión comentamos los avances principales logrados en el tratamiento de la FCU, incluyendo nuevas medidas sugeridas. Seguimos siendo optimistas con respecto a que una o más de las medidas potenciales que aquí revisamos, evolucionarán hacia futuras medicaciones para los pacientes con FCU.
Stereotactic Radiosurgery for Patients with Trigeminal Neuralgia Associated with Petroclival Meningiomas
Authors: Kano Hideyuki , Awan Nasir R. , Flannery Thomas J. , Iyer Aditya , Flickinger John C. , Lunsford L. Dade , Kondziolka Douglas
Published: December 2010

Background:The management of trigeminal neuralgia in patients with associated skull base meningiomas is complex. Objective:We evaluated the pain management needs and outcomes in patients with petroclival meningiomas associated with medically refractory trigeminal neuralgia. Methods: During a 21-year period, 168 patients underwent stereotactic radiosurgery (SRS) for meningiomas involving the petroclival region. We identified 12 patients (10 females; median age 54 years) who had trigeminal neuralgia in association with an ipsilateral petroclival meningioma. The median tumor volume was 3.8 cm3 (1.0–15.9 cm3). The median prescription dose for tumor margins was 13 Gy (11–16 Gy). Results: Initial pain control [Barrow Neurological Institute (BNI) grades I–IIIb] was obtained in 10 of 12 patients (83%). However, 3 patients with initial adequate relief later developed pain. Follow-up imaging revealed control of tumor growth in all patients at a median follow-up of 68 months. No patient developed any new sensory dysfunction. The tumor shrinkage was not associated with pain relief. At the final follow-up, 5 patients had pain of BNI grade I (2 after surgery), 4 had grade IIIb and 3 had grade IV. Conclusions: SRS provided effective tumor control, but trigeminal neuralgia persisted to varying degrees in most patients. Multimodality pain management strategies were required in most patients with skull base meningiomas associated with trigeminal neuralgia.
Ultrastructural and Immunocytochemical Analysis of Multilineage Differentiated Human Dental Pulp- and Umbilical Cord-Derived Mesenchymal Stem Cells
Authors: Struys T. , Moreels M. , Martens W. , Donders R. , Wolfs E. , Lambrichts I.
Published: December 2010

Mesenchymal stem cells (MSCs) are one of the most promising stem cell types due to their availability and relatively simple requirements for in vitro expansion and genetic manipulation. Besides the well-characterized MSCs derived from bone marrow, there is growing evidence suggesting that dental pulp and the umbilical cord matrix both contain a substantial amount of cells having properties similar to those of MSCs. In order to assess the potential of dental pulp-derived MSCs (DPSC) and umbilical cord-derived MSCs (UCSC) in future clinical applications, it is essential to gain more insight into their differentiation capacity and to evaluate the tissues formed by these cells. In the present study, the morphological and ultrastructural characteristics of DPSC and UCSC induced towards osteogenic, adipogenic, and chondrogenic lineages were investigated. Cultured DPSC and UCSC showed a similar expression pattern of antigens characteristic of MSCs including CD105, CD29, CD44, CD146, and STRO-1. Under appropriate culture conditions, both DPSC and UCSC showed chondrogenic and osteogenic potential. Adipogenesis could be only partially induced in DPSC resulting in the de novo expression of fatty acid binding protein (FABP), whereas UCSC expressed FABP combined with a very high accumulation of lipid droplets in the cytoplasm. Our results demonstrate, at the biochemical and ultrastructural level, that DPSC display at least bilineage potential, whereas UCSC, which are developmentally more primitive cells, show trilineage potential. We emphasize that transmission electron microscopical analysis is useful to elucidate detailed structural information and provides indisputable evidence of differentiation. These findings highlight their potential therapeutic value for cell-based tissue engineering.
The Impact of Single Gene and Chromosomal Disorders on Hospital Admissions of Children and Adolescents: A Population-Based Study
Authors: Dye D.E. , Brameld K.J. , Maxwell S. , Goldblatt J. , Bower C. , Leonard H. , Bourke J. , Glasson E.J. , O’Leary P.
Published: December 2010

Background: It is well recognized that genetic disease makes a significant contribution to childhood illness. Here, we present recent population data describing the impact of single gene and chromosomal disorders on hospital admissions of children and adolescents. Methods: Hospital admissions for patients aged 0–19 years between 2000 and 2006, with a single gene or chromosomal disorder, were extracted from the Western Australian Hospital Morbidity Data System using 296 diagnosis codes identified from the International Statistical Classification of Diseases, Tenth Revision, Australian Modification. Data extracted for each patient included the number, length and cost of all admissions. Results: Between 2000 and 2006, 14,197 admissions were identified for 3,271 patients aged 0–19 years with single gene and chromosomal disorders, representing 2.6% of admissions and 4.3% of total hospital costs in this age group. Patients with genetic disorders had more admissions and stayed longer in hospital than patients admitted for any reason. Specific disorders associated with a high demand on hospital services included cystic fibrosis, Down syndrome, osteogenesis imperfecta, thalassemia, and von Willebrand’s disease. Conclusions: Children and adolescents with single gene and chromosomal disorders placed higher demands on hospital services than other patients in their age group, but were responsible for a relatively small proportion of hospital admissions and costs. These data will enable informed planning of health care services for patients with single gene and chromosomal disorders in Western Australia.