bluuebunny/crossref_metadata_2025_split huggingface dataset:
Electrochemical Sensor for Multiplex Biomarkers Detection
Authors: Wei Fang , Patel Prabhudas , Liao Wei , Chaudhry Kishore , Zhang Lei , Arellano-Garcia Martha , Hu Shen , Elashoff David , Zhou Hui , Shukla Shilin , Shah Franky , Ho Chih-Ming , Wong David T. 
Published: June 2009

Abstract
Purpose: Multiplexing assay of biomarkers at the point-of-care is an elusive goal for molecular diagnostics.
Experimental Design: Here, we report an electrochemical (EC) sensor for oral cancer detection based on the simultaneous detection of two salivary biomarkers: interleukin (IL)-8 mRNA and IL-8 protein.
Results: Under the multiplexing mode, the limit of detection of salivary IL-8 mRNA reaches to 3.9 fM and 7.4 pg/mL for IL-8 protein in saliva. Multiplex assay of these 2 biomarkers directly from 28 cancer and 28 matched control saliva samples shows significant difference between the two groups. From the receiver operating characteristic analysis, the EC sensor yields around 90% sensitivity and specificity for both IL-8 mRNA and IL-8 protein, which are very close to the data measured by traditional assays (ELISA and PCR) with the same group of saliva. Combined IL-8 mRNA and protein show better AUC compared with single biomarker.
Conclusions: We show, for the first time, concurrently multiplexing detection of salivary mRNA and protein biomarkers using point-of-care EC sensor.
The Pyk2 FERM domain as a target to inhibit glioma migration
Authors: Loftus Joseph C. , Yang Zhongbo , Tran Nhan L. , Kloss Jean , Viso Carole , Berens Michael E. , Lipinski Christopher A. 
Published: June 2009

Abstract
The invasion of malignant glioma cells into the surrounding normal brain precludes effective clinical treatment. In this report, we investigated the role of the NH2-terminal FERM domain in the regulation of the promigratory function of Pyk2. We report that the substitution of residues that constitute a small cleft on the surface of the F3 module of the FERM domain do not significantly alter Pyk2 expression but result in the loss of Pyk2 phosphorylation. A monoclonal antibody, designated 12A10, specifically targeting the Pyk2 FERM domain was generated and recognizes an epitope located on the β5C-α1C surface of the F3 module of the FERM domain. Amino acid substitutions in the F3 module that resulted in the loss of Pyk2 phosphorylation also inhibited the binding of 12A10, suggesting that the 12A10 epitope overlaps a site that plays a role in Pyk2 activity. Conjugation of 12A10 to a membrane transport peptide led to intracellular accumulation and inhibition of glioma cell migration in a concentration-dependent manner. A single chain Fv fragment of 12A10 was stable when expressed in the intracellular environment, interacted directly with Pyk2, reduced Pyk2 phosphorylation, and inhibited glioma cell migration in vitro. Stable intracellular expression of the 12A10 scFv significantly extended survival in a glioma xenograft model. Together, these data substantiate a central role for the FERM domain in regulation of Pyk2 activity and identify the F3 module as a novel target to inhibit Pyk2 activity and inhibit glioma progression. [Mol Cancer Ther 2009;8(6):1505–14]
Lysophosphatidic acid stimulates cell migration, invasion, and colony formation as well as tumorigenesis/metastasis of mouse ovarian cancer in immunocompetent mice
Authors: Li Hui , Wang Dongmei , Zhang Hong , Kirmani Kashif , Zhao Zhenwen , Steinmetz Rosemary , Xu Yan 
Published: June 2009

Abstract
We have already established human xenographic models for the effect of lysophosphatidic acid (LPA) on tumor metastasis in vivo. The purpose of this work is to establish a preclinical LPA effect model in immunocompetent mice. We first characterized the mouse epithelial ovarian cancer (EOC) cell line ID8 for its responsiveness to LPA in cell proliferation, migration, and invasion and compared these properties with those of human EOC. The signaling pathways related to cell migration were further investigated using pharmacologic and genetic approaches. The effects of LPA on the tumorigenesis of ID8 cells and mouse survival were then examined using two different mouse models (i.p. and orthotopic injections). LPA stimulated cell proliferation, migration, and invasion of mouse EOC ID8 cells in a manner closely resembling its activity in human EOC cells. The signaling pathways involved in LPA-induced cell migration in ID8 cells were also similar to those identified in human EOC cells. We have identified cyclooxygenase-1 and 15-lipoxygenase as two new signaling molecules involved in LPA-induced cell migration in both human and mouse EOC cells. In addition, LPA enhanced the tumorigenesis/metastasis of ID8 cell in vivo as assessed by increased tumor size, early onset of ascites formation, and reduced animal survival. We have established the first LPA-EOC preclinical model in immunocompetent mice. Because ID8 cells respond to LPA similar to human EOC cells, this model is very valuable in developing and testing therapeutic reagents targeting LPA in EOC. [Mol Cancer Ther 2009;8(6):1692–701]
Rac1 contributes to trastuzumab resistance of breast cancer cells: Rac1 as a potential therapeutic target for the treatment of trastuzumab-resistant breast cancer
Authors: Dokmanovic Milos , Hirsch Dianne S. , Shen Yi , Wu Wen Jin 
Published: June 2009

AbstractAlthough treatment with trastuzumab improves outcomes for women with ErbB2-positive breast cancer, many patients who achieve an initial response to trastuzumab subsequently acquire resistance within 1 year. Rac1, a Ras-like small GTPase, has been implicated in the control of cell growth and morphology and is believed to be associated with breast cancer progression and metastasis. Here, we show that when parental SKBR3 cells become resistant to trastuzumab, Rac1 activity is increased, leading to altered cell morphology, which is accompanied by significant cytoskeleton disorganization. Furthermore, both trastuzumab-mediated down-regulation of ErbB2 and epidermal growth factor–induced down-regulation of epidermal growth factor receptor are impaired in the trastuzumab-resistant SKBR3 cells, indicating that the endocytic down-regulation of ErbB receptors is compromised in the resistant cells. This results in an aberrant accumulation of ErbB2 on the cell surface and enhanced ErbB2 and extracellular signal-regulated kinase activity in trastuzumab-resistant SKBR3 cells. Additionally, overexpression of constitutively active Rac1G12V in parental SKBR3 cells reduces sensitivity to trastuzumab. After reduction of Rac1 activity by NSC23766, a specific Rac1 inhibitor, trastuzumab-resistant SKBR3 cells display a cellular morphology similar to parental SKBR3 cells. Moreover, we show that NSC23766 restores trastuzumab-mediated endocytic down-regulation of ErbB2 and reduces extracellular signal-regulated kinase activity in resistant SKBR3 cells. Our findings highlight an important role for Rac1 in trastuzumab resistance of human breast cancer cells and identify the impaired trastuzumab-mediated endocytic down-regulation of ErbB2 as a novel mechanism of trastuzumab resistance. The significant effects of NSC23766 on trastuzumab-resistant SKBR3 cells warrant further study of NSC23766 as a potential treatment of trastuzumab-resistant breast cancers. [Mol Cancer Ther 2009;8(6):1557–69]
Engineering a leucine zipper-TRAIL homotrimer with improved cytotoxicity in tumor cells
Authors: Rozanov Dmitri V. , Savinov Alexei Y. , Golubkov Vladislav S. , Rozanova Olga L. , Postnova Tatiana I. , Sergienko Eduard A. , Vasile Stefan , Aleshin Alexander E. , Rega Michele F. , Pellecchia Maurizio , Strongin Alex Y. 
Published: June 2009

AbstractSuccessful cancer therapies aim to induce selective apoptosis in neoplastic cells. The current suboptimal efficiency and selectivity drugs have therapeutic limitations and induce concomitant side effects. Recently, novel cancer therapies based on the use of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) have emerged. TRAIL, a key component of the natural antitumor immune response, selectively kills many tumor cell types. Earlier studies with recombinant TRAIL, however, revealed its many shortcomings including a short half-life, off-target toxicity, and existence of TRAIL-resistant tumor cells. We improved the efficacy of recombinant TRAIL by redesigning its structure and the expression and purification procedures. The result is a highly stable leucine zipper (LZ)-TRAIL chimera that is simple to produce and purify. This chimera functions as a trimer in a manner that is similar to natural TRAIL. The formulation of the recombinant LZ-TRAIL we have developed has displayed high specific activity in both cell-based assays in vitro and animal tests in vivo. Our results have shown that the half-life of LZ-TRAIL is improved and now exceeds 1 h in mice compared with a half-life of only minutes reported earlier for recombinant TRAIL. We have concluded that our LZ-TRAIL construct will serve as a foundation for a new generation of fully human LZ-TRAIL proteins suitable for use in preclinical and clinical studies and for effective combination therapies to overcome tumor resistance to TRAIL. [Mol Cancer Ther 2009;8(6):1515–]
The Effect of Tunnel Placement on Bone-Tendon Healing in Anterior Cruciate Ligament Reconstruction in a Goat Model
Authors: Ekdahl Max , Nozaki Masahiro , Ferretti Mario , Tsai Andrew , Smolinski Patrick , Fu Freddie H. 
Published: June 2009

Background Misplacement of the bone tunnels is one of the main causes of graft failure of anterior cruciate ligament surgery. Hypothesis Anatomic tunnel placement in anterior cruciate ligament surgery reconstruction will lead to improved outcomes, including biological ingrowth and biomechanical properties, when compared with nonanatomic tunnel placement. Study Design Controlled laboratory study. Methods Anterior cruciate ligament surgery reconstructions were performed on 3 different groups of goats (1 anatomic tunnel placement group and 2 different nonanatomic tunnel placement groups, with 10 goats in each group). For each group of 10 knees, 3 knees were used for histologic evaluation (bone tunnel enlargement, number of osteoclasts at the bone tendon interface, and revascularization of the graft) and 7 knees were used for biomechanical testing (anterior tibial translation, in situ force, cross-sectional area, and ultimate failure load). Animals were sacrificed at 12 weeks after surgery. Results The anatomic tunnel placement group showed less tunnel enlargement on the tibial side, fewer osteoclasts on both the tibial and femoral sides, and more vascularity in the femoral side when compared with the 2 nonanatomic reconstruction groups. Biomechanically, the anatomic tunnel placement group demonstrated less anterior tibial translation and greater in situ force than both nonanatomic tunnel placement groups. Conclusion Anatomic tunnel placement leads to superior biological healing and biomechanical properties compared with nonanatomic placement at 12 weeks after anterior cruciate ligament surgery reconstruction in a goat model. Clinical Relevance The findings of this study demonstrate the importance of anatomic tunnel placement in anterior cruciate ligament surgery reconstruction.
Clinical Utility of Traditional and New Tests in the Diagnosis of Biceps Tendon Injuries and Superior Labrum Anterior and Posterior Lesions in the Shoulder
Authors: Ben Kibler W. , Sciascia Aaron D. , Hester Peter , Dome David , Jacobs Cale 
Published: June 2009

Background Clinical tests are a key element in diagnosing shoulder lesions. Purpose This study examined the clinical utility of traditional and new examination tests, the upper cut for biceps injuries, and the modified dynamic labral shear for superior glenoid labral lesions. Study Design Cohort study (Diagnosis); Level of evidence, 2. Methods A total of 325 consecutive patients who were seen for shoulder pain underwent a standardized clinical testing battery. Six clinical tests that have been previously reported in the literature (Yergason's, Speed's, bear hug, belly press, O'Brien's, and anterior slide) and 2 new examination tests (upper cut and modified dynamic labral shear) were performed. Clinical examination findings were correlated with findings in those who came to surgery (101 patients). Sensitivity, specificity, accuracy, positive/ negative predictive value, and positive/negative likelihood ratio were calculated for each test. A binary logistic regression analysis was used to determine which tests produced the most significant findings. Results For biceps disease, the bear hug and upper cut were most sensitive (0.79 and 0.73, respectively), whereas the belly press and Speed's test were most specific (0.85 and 0.81, respectively). The upper cut was most accurate (0.77) and produced the highest positive likelihood ratio (3.38). For labral injury, the modified dynamic labral shear demonstrated sensitivity of 0.72, specificity of 0.98, accuracy of 0.84, and a positive likelihood ratio of 31.57. A binary logistic regression analysis revealed that the combination of the upper cut and Speed's tests were significantly better at detecting biceps lesions (P = .021, R2 = .400) than other tests, whereas labral lesions were best identified by combination of the modified dynamic labral shear and O'Brien's maneuvers (P = .045, R2 = .641). Conclusion The new tests are helpful additions to the clinical examination for shoulder injury. The modified dynamic labral shear test demonstrates high scores for clinical utility and exhibits a high likelihood ratio, indicating a significant probability of affecting the clinical decision, which should moderately or significantly improve the diagnostic conclusion and allow the clinician to be more efficient in making an accurate diagnosis.
PDU Bundling and Replication for Reduction of Distributed Simulation Communication Traffic
Authors: Vargas Juan J. , DeMara Ronald F. , Georgiopoulos Michael , Gonzalez Avelino J. , Marshall Henry 
Published: June 2009

Communication bandwidth and latency reduction techniques are developed for Distributed Interactive Simulation (DIS) protocols. DIS Protocol Data Unit (PDU) packets are bundled together prior to transmission based on PDU type, internal structure, and content over a sliding window of up to C adjacent transmission requests, for 1 < C < 64. At the receiving nodes, the packets are replicated as necessary to reconstruct the original packet stream. Bundling strategies including Always-Wait, Always-Send, Type-Only prediction, Type-Length prediction, and Type-Length-Time prediction are developed and then evaluated using both heuristic parameters and a gradient descent back-propagation neural network. Several communication case studies from the One Semi-Automated Forces (OneSAF) Testbed Baseline (OTB) are assessed for multiple-platoon, company, and battalion-scale force-on-force vignettes consistent with Future Combat Systems (FCS) Operations and Organizations (O&O) scenarios. Traffic is modeled using the OMNeT++ discrete-event simulator models and scripts developed for a hierarchical communication architecture consisting of eight en route C-17 aircraft, each carrying three Ethernet-connected M1A2 ground vehicles, a wireless flying LAN based on Joint Forces Command's Joint En route Mission Planning and Rehearsal System (JEMPRS) for Near-Term (JEMPRS-NT) and follow-on bandwidth capacities. The simulation traffic includes Opposing Force (OPFOR) control through a CONUS-based ground station via its corresponding satellite links. Different bandwidth capacities are simulated and analyzed for PDU travel time and slack time, router and satellite queue length, and number of packet collisions are assessed at 64 Kbps, 256 Kbps, 512 Kbps, and 1 Mbps capacities. Results indicate that a Type-Length prediction strategy is capable of improving travel time up to 85%, slack time up to 97%, and queue length up to 98% on bandwidth restricted channels of 64 Kbps.
Modeling Homeland Security
Authors: Pruitt Kristopher A. , Deckro Richard F. , Chambal Stephen P. 
Published: June 2009

The events of September 11, 2001, have propelled the topic of homeland security to the forefront of national concern. The threat of terrorism within the United States has reached an unprecedented level. The potential vulnerabilities present in the nation's critical infrastructure, coupled with the destructive capabilities and deadly intentions of modern terrorists, pose extraordinary risks. The United States must mitigate these risks while at the same time balancing the associated costs and impact on civil liberties. Currently, there is a need for effective methods and measures for assessing the security of the homeland from acts of terrorism at the aggregate, national level. This study develops a first-cut decision-analysis-based methodology for identifying and structuring key homeland security capabilities and facilitating the measurement of the United States' capability to execute these required capabilities.
Dynamic Decision Support in the Advanced Tactical Architecture for Combat Knowledge System
Authors: Momen Faisal , Rozenblit Jerzy W. 
Published: June 2009

As modern military systems demand faster reactions and become more mobile, the difference between planning and execution will fade until the planning process appears to merge with the battle management process. Continuous planning systems must be fast, intuitive, and accurate. In particular, the amount of information will be overwhelming and the number of options unmanageable for many future tactical environments. The Advanced Tactical Architecture for Combat Knowledge System (ATACKS) has been designed to incorporate both visualization tools and intelligent algorithms to allow for rapid visualization and decision making in these military environments. The work presented in this paper demonstrates how an external, intelligent system, in this case a system based on the Discrete Event System Specification (DEVS) framework, was adapted and successfully integrated with ATACKS to produce dynamic decision support for battlefield visualization in a distributed environment. The DEVS decision support application was designed to provide recommendations on the feasibility of proposed courses of action enacted in ATACKS. By querying the appropriate unit models, it derives the state of the current battle. Subsequently, DEVS uses its wargaming rules to formulate a Go or No-Go decision, which is communicated back to the commander working with ATACKS.
Fatty acid patterns early after premature birth, simultaneously analysed in mothers' food, breast milk and serum phospholipids of mothers and infants
Authors: Sabel Karl-Göran , Lundqvist-Persson Cristina , Bona Elsa , Petzold Max , Strandvik Birgitta 
Published: June 2009

Abstract

Background
The supply of long-chain polyunsaturated fatty acids via the placenta is interrupted in premature infants, making them exclusively dependent on breast milk, which varies in fatty acid (FA) concentrations depending on the mother's diet.

Objective
To in a longitudinal study explore the relation between FA status in mothers and infants from an unselected cohort of prematures, not requiring intensive care.

Design
Breast milk and mothers' and infants' plasma phospholipid FA concentrations from birth to 44 weeks of gestational age were analysed and compared with mothers' food intake, assessed using a 3-day diary. Fatty acids were analysed by capillary gas-liquid chromatography.

Results
The energy intake was low in 75% of mothers, and 90% had low intake of essential FAs (EFAs). Dietary linoleic acid (LA, 18:2w6), but not w3 FAs, correlated to concentrations in breast milk. Infants' plasma and breast milk correlated for arachidonic (AA, 20:4w6), eicosapentaenoic (EPA, 20:5w3) and docosahexaenoic (DHA, 22:6w3) acids. A high concentration of mead acid (20:3w9) in the infants at birth correlated negatively to the concentrations of LA, AA and w3 FAs. Infants of mothers who stopped breastfeeding during the study period showed decreased DHA concentrations and increased w6/w3 ratios, with the opposite FA pattern seen in the mothers' plasma.

Conclusion
Although dietary w3 FAs were insufficient in an unselected cohort of mothers of premature infants, breastfeeding resulted in increased levels of DHA in the premature infants at the expense of the mothers, suggesting a general need to increase dietary w3 FAs during pregnancy and lactation.
Characterization of a potent non-cytotoxic shRNA directed to the HIV-1 co-receptor CCR5
Authors: Shimizu Saki , Kamata Masakazu , Kittipongdaja Panyamol , Chen Kevin N , Kim Sanggu , Pang Shen , Boyer Joshua , Qin F Xiao-Feng , An Dong Sung , Chen Irvin SY 
Published: June 2009

Abstract

Background
The use of shRNAs to downregulate the expression of specific genes is now relatively routine in experimentation but still hypothetical for clinical application. A potential therapeutic approach for HIV-1 disease is shRNA mediated downregulation of the HIV-1 co-receptor, CCR5. It is increasingly recognized that siRNAs and shRNAs can have unintended consequences such as cytotoxicities in cells, particularly when used for long term therapeutic purposes. For the clinical use of shRNAs, it is crucial to identify a shRNA that can potently inhibit CCR5 expression without inducing unintended cytotoxicities.

Results
Previous shRNAs to CCR5 identified using conventional commercial algorithms showed cytotoxicity when expressed using the highly active U6 pol III promoter in primary human peripheral blood derived mononuclear cells. Expression using the lower activity H1 promoter significantly reduced toxicity, but all shRNAs also reduced RNAi activity. In an effort to identify shRNAs that were both potent and non-cytotoxic, we created a shRNA library representing all potential CCR5 20 to 22-nucleotide shRNA sequences expressed using an H1 promoter and screened this library for downregulation of CCR5. We identified one potent CCR5 shRNA that was also non-cytotoxic when expressed at a low level with the H1 promoter. We characterized this shRNA in regards to its function and structure. This shRNA was unique that the use of commercial and published algorithms to predict effective siRNA sequences did not result in identification of the same shRNA. We found that this shRNA could induce sequence specific reduction of CCR5 at post transcriptional level, consistent with the RNA interference mechanism. Importantly, this shRNA showed no obvious cytotoxicity and was effective at downregulating CCR5 in primary human peripheral blood derived mononuclear cells.

Conclusion
We report on the characterization of a rare shRNA with atypical structural features having potent RNAi activity specific to CCR5. These results have implications for the application of RNAi technology for therapeutic purposes.
Synthesis and Structural Characterization of a Novel Three-dimensional Molybdenum–Oxygen Framework Constructed from Mo3O9 Units
Authors: Zhao Junwei , Ma Pengtao , Wang Jingping , Niu Jingyang 
Published: June 2009

Abstract
A novel three-dimensional molybdenum oxide Mo3O9·H2O (1) constructed from Mo3O9 units has been successfully synthesized under hydrothermal conditions and structurally characterized by IR spectrum, inductively coupled plasma (ICP) analysis, powder X-ray diffraction (PXRD), X-ray photoelectron spectroscopy (XPS), and single-crystal X-ray diffraction.