bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular profiling of cutaneous squamous cell carcinomas and actinic keratoses from organ transplant recipients
Authors: Hameetman Liesbeth , Commandeur Suzan , Bavinck Jan Nico Bouwes , Wisgerhof Hermina C , de Gruijl Frank R , Willemze Rein , Mullenders Leon , Tensen Cornelis P , Vrieling Harry
Published: February 2013

Background

The risk of developing cutaneous squamous cell carcinoma (SCC) is markedly increased in organ transplant recipients (OTRs) compared to the normal population. Next to sun exposure, the immunosuppressive regimen is an important risk factor for the development of SCC in OTRs. Various gene mutations (e.g. TP53) and genetic alterations (e.g. loss of CDKN2A, amplification of RAS) have been found in SCCs. The aim of this genome-wide study was to identify pathways and genomic alterations that are consistently involved in the formation of SCCs and their precursor lesions, actinic keratoses (AKs).

Methods

To perform the analysis in an isogenic background, RNA and DNA were isolated from SCC, AK and normal (unexposed) epidermis (NS) from each of 13 OTRs. Samples were subjected to genome-wide expression analysis and genome SNP analysis using Illumina’s HumanWG-6 BeadChips and Infinium II HumanHap550 Genotyping BeadChips, respectively. mRNA expression results were verified by quantitative PCR.

Results

Hierarchical cluster analysis of mRNA expression profiles showed SCC, AK and NS samples to separate into three distinct groups. Several thousand genes were differentially expressed between epidermis, AK and SCC; most upregulated in SCCs were hyperproliferation related genes and stress markers, such as keratin 6 (KRT6), KRT16 and KRT17. Matching to oncogenic pathways revealed activation of downstream targets of RAS and cMYC in SCCs and of NFκB and TNF already in AKs. In contrast to what has been reported previously, genome-wide SNP analysis showed very few copy number variations in AKs and SCCs, and these variations had no apparent relationship with observed changes in mRNA expression profiles.

Conclusion

Vast differences in gene expression profiles exist between SCC, AK and NS from immunosuppressed OTRs. Moreover, several pathways activated in SCCs were already activated in AKs, confirming the assumption that AKs are the precursor lesions of SCCs. Since the drastic changes in gene expression appeared unlinked to specific genomic gains or losses, the causal events driving SCC development require further investigation. Other molecular mechanisms, such as DNA methylation or miRNA alterations, may affect gene expression in SCCs of OTRs. Further study is required to identify the mechanisms of early activation of NFκB and TNF, and to establish whether these pathways offer a feasible target for preventive intervention among OTRs.
Up-regulated microRNA-143 in cancer stem cells differentiation promotes prostate cancer cells metastasis by modulating FNDC3B expression
Authors: Fan Xinlan , Chen Xu , Deng Weixi , Zhong Guangzheng , Cai Qingqing , Lin Tianxin
Published: February 2013

Background

Metastatic prostate cancer is a leading cause of cancer-related death in men. Cancer stem cells (CSCs) are involved in tumor progression and metastasis, including in prostate cancer. There is an obvious and urgent need for effective cancer stem cells specific therapies in metastatic prostate cancer. MicroRNAs (miRNAs) are an important class of pervasive genes that are involved in a variety of biological functions, especially in cancer. The goal of this study was to identify miRNAs involved in prostate cancer metastasis and cancer stem cells.

Methods

A microarray and qRT-PCR were performed to investigate the miRNA expression profiles in PC-3 sphere cells and adherent cells. A transwell assay was used to evaluate the migration of PC-3 sphere cells and adherent cells. MiR-143 was silenced with antisense oligonucleotides in PC-3, PC-3-M and LNCaP cells. The role of miR-143 in prostate cancer metastasis was measured by wound-healing and transwell assays in vitro and bioluminescence imaging in vivo. Bioinformatics and luciferase report assays were used to identify the target of miR-143.

Results

The expression of miR-143 and the migration capability were reduced in PC-3 sphere cells and progressively increased during sphere re-adherent culture. Moreover, the down-regulation of miR-143 suppressed prostate cancer cells migration and invasion in vitro and systemically inhibited metastasis in vivo. Fibronectin type III domain containing 3B (FNDC3B), which regulates cell motility, was identified as a target of miR-143. The inhibition of miR-143 increased the expression of FNDC3B protein but not FNDC3B mRNA in vitro and vivo.

Conclusions

These data demonstrate for the first time that miR-143 was up-regulated during the differentiation of prostate cancer stem cells and promoted prostate cancer metastasis by repressing FNDC3B expression. This sheds a new insight into the post-transcriptional regulation of cancer stem cells differentiation by miRNAs, a potential approach for the treatment of prostate cancer.
Hyaluronic acid affects the in vitro induction effects of Synthetic PAMPS and PDMAAm hydrogels on chondrogenic differentiation of ATDC5 cells, depending on the level of concentration
Authors: Yoshikawa Katsuhisa , Kitamura Nobuto , Kurokawa Takayuki , Gong Jian Ping , Nohara Yutaka , Yasuda Kazunori
Published: February 2013

Background

It has been a common belief that articular cartilage tissue cannot regenerate in vivo. Recently, however, we have found that spontaneous hyaline cartilage regeneration can be induced in vivo by implanting a synthetic double-network (DN) hydrogel, which is composed of poly-(2-acrylamido-2-methylpropanesulfonic acid) (PAMPS) and poly-(N,N’-dimethyl acrylamide) (PDMAAm). However, the mechanism of this phenomenon has not been clarified. Recently, we have found that single-network PAMPS and PDMAAm gels can induce chondrogenic differentiation of ATDC5 cells in vitro even in a maintenance medium. In the in vivo condition, there is a strong possibility that the induction effect of the gel itself is enhanced by some molecules which exist in the joint. We have noticed that the joint fluid naturally contains hyaluronic acid (HA). The purpose of this study is to clarify in vitro effects of supplementation of HA on the differentiation effect of the PAMPS and PDMAAm gels.

Methods

We cultured the ATDC5 cells on the PAMPS gel, the PDMAAm gel, and the polystyrene (PS) dish surface with the maintenance medium without insulin for 7 days. HA having a molecular weight of approximately 800 kDa was supplemented into the medium so that the concentration became 0.00, 0.01, 0.10, or 1.00 mg/mL. We evaluated the cultured cells with phase-contrast microscopy and PCR analyses.

Results

On the PAMPS gel, supplementation with HA of 0.01 and 0.10 mg/mL significantly increased expression of type-2 collagen mRNA (p = 0.0008 and p = 0.0413) and aggrecan mRNA (p = 0.0073 and p = 0.0196) than that without HA. On the PDMAAm gel, supplementation with HA of 1.00 mg/mL significantly reduced expression of these genes in comparison with the culture without HA (p = 0.0426 and p = 0.0218).

Conclusions

The in vitro induction effects of the PAMPS and PDMAAm gels on chondrogenic differentiation of ATDC5 cells are significantly affected by HA, depending on the level of concentration. These results suggested that there is a high possibility that HA plays an important role in the in vivo spontaneous hyaline cartilage regeneration phenomenon induced by the PAMPS/PDMAAm DN gel.
Production of α-cuprenene in Xanthophyllomyces dendrorhous: a step closer to a potent terpene biofactory
Authors: Melillo Elena , Setroikromo Rita , Quax Wim J , Kayser Oliver
Published: February 2013

Background

The red yeast Xanthophyllomyces dendrorhous is a natural producer of the carotenoid astaxanthin. Because of its high flux, the native terpene pathway leading to the production of the tetraterpene is of particular interest as it can be redirected toward the production of other terpene compounds. The genetic tools for the transformation of the yeast with the concurrent knock-out of genes involved in the astaxanthin biosynthesis are made available and here we show that the production of the sesquiterpene α-cuprenene is possible in mutant strains of X. dendrorhous transformed with the Cop6 gene originating from the fungus Coprinus cinereus. For the evaluation of the production levels, we chose to express the same gene and analyze the accumulation of α-cuprenene in Escherichia coli and Saccharomyces cerevisiae, as well. Here we propose that X. dendrorhous is a candidate in the search for the potential platform organism for the production of terpenes.

Results

All three X. dendrorhous mutants functionally express the Cop6 gene and accumulate α-cuprenene. The production of α-cuprenene in the red yeast reached 80 mg/L, which represents a far higher concentration compared to the levels obtained in the E. coli and S. cerevisiae mutants. At this expression levels the pool of terpene precursors has not become a limiting factor in the X. dendrorhous mutants since the expression of the Cop6 gene in the genomic rDNA of the yeast allows production of both α-cuprenene and astaxanthin without affecting the growth or the accumulation levels of both compounds.

Conclusions

We have shown that X. dendrorhous can produce α-cuprenene, and the results here presented, next to the capability of accumulating at least two more non-native sesquiterpenes, demonstrates the high potential of this yeast to become an interesting terpene-based drugs producer.
Methods for implementing a medicine outlet survey: lessons from the anti-malarial market
Authors: O’Connell Kathryn A , Poyer Stephen , Solomon Tsione , Munroe Erik , Patouillard Edith , Njogu Julius , Evance Illah , Hanson Kara , Shewchuk Tanya , Goodman Catherine
Published: February 2013

Background

In recent years an increasing number of public investments and policy changes have been made to improve the availability, affordability and quality of medicines available to consumers in developing countries, including anti-malarials. It is important to monitor the extent to which these interventions are successful in achieving their aims using quantitative data on the supply side of the market. There are a number of challenges related to studying supply, including outlet sampling, gaining provider cooperation and collecting accurate data on medicines. This paper provides guidance on key steps to address these issues when conducting a medicine outlet survey in a developing country context. While the basic principles of good survey design and implementation are important for all surveys, there are a set of specific issues that should be considered when conducting a medicine outlet survey.

Methods

This paper draws on the authors’ experience of designing and implementing outlet surveys, including the lessons learnt from ACTwatch outlet surveys on anti-malarial retail supply, and other key studies in the field. Key lessons and points of debate are distilled around the following areas: selecting a sample of outlets; techniques for collecting and analysing data on medicine availability, price and sales volumes; and methods for ensuring high quality data in general.

Results and conclusions

The authors first consider the inclusion criteria for outlets, contrasting comprehensive versus more focused approaches. Methods for developing a reliable sampling frame of outlets are then presented, including use of existing lists, key informants and an outlet census. Specific issues in the collection of data on medicine prices and sales volumes are discussed; and approaches for generating comparable price and sales volume data across products using the adult equivalent treatment dose (AETD) are explored. The paper concludes with advice on practical considerations, including questionnaire design, field worker training, and data collection. Survey materials developed by ACTwatch for investigating anti-malarial markets in sub-Saharan Africa and Asia provide a helpful resource for future studies in this area.
High frequency of CRB1 mutations as cause of Early-Onset Retinal Dystrophies in the Spanish population
Authors: Corton Marta , Tatu Sorina D , Avila-Fernandez Almudena , Vallespín Elena , Tapias Ignacio , Cantalapiedra Diego , Blanco-Kelly Fiona , Riveiro-Alvarez Rosa , Bernal Sara , García-Sandoval Blanca , Baiget Montserrat , Ayuso Carmen
Published: February 2013

Background

CRB1 mutations are reported as cause of severe congenital and early-onset retinal dystrophies (EORD) with different phenotypic manifestations, including Leber congenital amaurosis (LCA), retinitis pigmentosa (RP) and cone-rod dystrophies. Comprehensive mutational scanning of the whole gene has been only performed in few cohorts, mainly in LCA patients. Here, we aimed investigating the real prevalence of CRB1 mutations in the Spanish population by extensive screening of CRB1 mutations in a large cohort of LCA and EORP cases.

Methods

This report integrates data from previous studies on CRB1 defects in our Spanish cohort of LCA and early-onset RP (EORP) with new findings from a comprehensive mutational screening of the whole gene. The molecular tools used include mutation genotyping arrays, whole-genome homozygosity mapping, an optimized high-resolution melting (HRM) analysis and Sanger sequencing.

Results

A large clinically well-characterized cohort of 404 Spanish cases was studied, 114 of which suffered from LCA and 290 from EORP. This study reveals that 11% of Spanish patients carried mutations in CRB1, ranging from 9% of EORP to 14% of LCA cases. More than three quarters of the mutations identified herein have been first described in this Spanish cohort, 13 of them are unreported new variants and 13 had been previously reported in our previous studies.

Conclusions

This work provides a wide spectrum of CRB1 mutations in the Spanish EORD patients and evidences the major role of CRB1 as causal gene in the Spanish EORP patients. It is noteworthy that a high rate of private mutations only described in our cohort has been found so far. To our knowledge, this study represents the most complete mutational screening of CRB1 in a Spanish LCA and EORP cohort, allowing us to establish gene-specific frequencies and to provide a wide spectrum of CRB1 mutations in the Spanish population.
Production of latex agglutination reagents for pneumococcal serotyping
Authors: Ortika Belinda D , Habib Maha , Dunne Eileen M , Porter Barbara D , Satzke Catherine
Published: February 2013

Background

The current ‘gold standard’ for serotyping pneumococci is the Quellung test. This technique is laborious and requires a certain level of training to correctly perform. Commercial pneumococcal latex agglutination serotyping reagents are available, but these are expensive. In-house production of latex agglutination reagents can be a cost-effective alternative to using commercially available reagents. This paper describes a method for the production and quality control (QC) of latex reagents, including problem solving recommendations, for pneumococcal serotyping.

Results

Here we describe a method for the production of latex agglutination reagents based on the passive adsorption of antibodies to latex particles. Sixty-five latex agglutination reagents were made using the PneuCarriage Project (PCP) method, of which 35 passed QC. The other 30 reagents failed QC due to auto-agglutination (n=2), no reactivity with target serotypes (n=8) or cross-reactivity with non-target serotypes (n=20). Dilution of antisera resulted in a further 27 reagents passing QC. The remaining three reagents passed QC when prepared without centrifugation and wash steps. Protein estimates indicated that latex reagents that failed QC when prepared using the PCP method passed when made with antiserum containing ≤ 500 μg/ml of protein. Sixty-one nasopharyngeal isolates were serotyped with our in-house latex agglutination reagents, with the results showing complete concordance with the Quellung reaction.

Conclusions

The method described here to produce latex agglutination reagents allows simple and efficient serotyping of pneumococci and may be applicable to latex agglutination reagents for typing or identification of other microorganisms. We recommend diluting antisera or removing centrifugation and wash steps for any latex reagents that fail QC. Our latex reagents are cost-effective, technically undemanding to prepare and remain stable for long periods of time, making them ideal for use in low-income countries.
Prognostic factors for metastatic cutaneous squamous cell carcinoma of the parotid
Authors: Makki Fawaz M , Mendez Adrian I , Taylor S Mark , Trites Jonathan , Bullock Martin , Flowerdew Gordon , Hart Robert D
Published: February 2013

Objective

To explore the prognostic significance of patient and disease characteristics on the survival of patients with metastatic cutaneous squamous cell carcinoma of the parotid gland at a tertiary care center in Halifax, Nova Scotia, Canada.

Methods

A retrospective chart review for all patients diagnosed with metastatic cutaneous squamous cell carcinoma to the parotid gland from January 2000 to December 2010. Multiple variables were examined related to: patient demographics, surgical details, non-surgical procedure details, and tumor pathologic description.

Results

A total of 54 patients [48 men (88%) and 6 women (12%)], with a median age at surgery of 78 years (range 47–93 years) were included in the study. All patients had a minimum follow up of 12 months or until deceased, with a median duration of follow up of 24 months. Predictors that were significant for cancer recurrence were pretreatment N-stage, pathologic neck node status, total number of positive neck nodes, and perineural invasion. Predictors that were significant for cancer death were the total number of positive neck nodes and perineural invasion. The remainder of the predictors including margin status were non-significant. Only age and nodal status were significant for both cancer death and recurrence on multivariate analysis.

Conclusion

Our results showed only two variables that remained significant on multivariate analysis were age and number of involved neck nodes, this finding suggests that re-resection of positive margins may not be necessary and that radiation therapy is the mainstay of treatment for positive margins.
Pancreatic cyst development: insights from von Hippel-Lindau disease
Authors: van Asselt Sophie J , de Vries Elisabeth GE , van Dullemen Hendrik M , Brouwers Adrienne H , Walenkamp Annemiek ME , Giles Rachel H , Links Thera P
Published: February 2013

Pancreatic cysts are a heterogeneous group of lesions, which can be benign or malignant. Due to improved imaging techniques, physicians are more often confronted with pancreatic cysts. Little is known about the origin of pancreatic cysts in general. Von Hippel-Lindau (VHL) disease is an atypical ciliopathy and inherited tumor syndrome, caused by a mutation in the VHL tumor suppressor gene encoding the VHL protein (pVHL). VHL patients are prone to develop cysts and neuroendocrine tumors in the pancreas in addition to several other benign and malignant neoplasms. Remarkably, pancreatic cysts occur in approximately 70% of VHL patients, making it the only hereditary tumor syndrome with such a discernible expression of pancreatic cysts. Cellular loss of pVHL due to biallelic mutation can model pancreatic cystogenesis in other organisms, suggesting a causal relationship. Here, we give a comprehensive overview of various pVHL functions, focusing on those that can potentially explain pancreatic cyst development in VHL disease. Based on preclinical studies, cilia loss in ductal cells is probably an important early event in pancreatic cyst development.
An introduction to this special section: Chronostratigraphy
Authors: Stark Tracy J. , Zeng Hongliu , Jackson Alan
Published: February 2013

In 1977, we saw the publication of AAPG Memoir 26, Seismic Stratigraphy—Applications to Hydrocarbon Exploration. In this book, Peter Vail and his colleagues, in a series of papers, introduced the industry to the concepts of seismic sequences, the construction of chronostratigraphic charts, and how the seismic data could be used to estimate the global rise and fall of sea level. In this work, they also showed how the shape of the reflections and their lapping relationships could be used to predict depositional environment, which could be used to predict sediment type and facies.
Stratal slice: The next generation
Authors: Zeng Hongliu
Published: February 2013

Vail and his colleagues (1977a, b) laid a foundation for seismic chronostratigraphy. By analyzing the relative rise of sea level indicated by coastal onlap, these workers invented a novel way of converting a stratigraphic cross section in the depth or traveltime domain to a chronostratigraphic chart in the Wheeler domain (Figure 1a and Figure 1b). With the widespread use of seismic data in the industry, such conversion can now be achieved conveniently with the proper software at the basinal, regional, or prospect scale (Figure 1c and Figure 1d).
Domain transform: A tool for imaging and interpreting geomorphology and stratigraphy in seismic volumes
Authors: Dorn Geoffrey A.
Published: February 2013

The presence of complex structure on seismic data often makes it difficult to recognize and interpret depositional systems in the volume. A number of techniques, under the broad topic of chronostratigraphy, have been developed in recent years to address this problem and enable more complete imaging and interpretation of seismic geomorphology and stratigraphy. A “domain transform” (DT) is an interpretation-guided process designed to remove some or all structural deformation from a seismic volume. It improves the imaging of paleo-depositional systems by creating a volume that consists of approximations of paleo-depositional surfaces. Such volumes are ideal for imaging, analysis, and interpretation of seismic geomorphology and stratigraphy.
Lost WWII fighter in Egypt offers lesson in varied uses of satellite imagery
Authors: Corbley Kevin
Published: February 2013

Word spread quickly in Egypt that a Polish exploration group had discovered a fighter plane that had crash- landed in the Western Desert during World War II. The remarkably well-preserved condition of the aircraft (guns and ammunition still intact) led the explorationists to conclude they were the first to see it since the war. Just days after the reported discovery in March 2012, experienced Egyptian desert guide Mohamed Abdel Aziz wanted to confirm the find for himself. While taking a group of recreational off-road motorcyclists into the remote desert near the Farafra Oasis, he too located the wreckage. Abdel Aziz realized the pilot must have survived the crash but likely didn't live long in the barren terrain. A cursory search of the area failed to locate any remains.
Steroid-Sparing Effect of Corticorelin Acetate in Peritumoral Cerebral Edema Is Associated With Improvement in Steroid-Induced Myopathy
Authors: Recht Lawrence , Mechtler Laszlo L. , Wong Eric T. , O'Connor Patrick C. , Rodda Bruce E.
Published: February 2013

Purpose

To compare the safety and efficacy of corticorelin acetate (CrA) and placebo in patients with malignant brain tumors requiring chronic administration of dexamethasone (DEX) to control the signs and symptoms of peritumoral brain edema (PBE).

Patients and Methods

Prospective, randomized, double-blind study of 200 patients with PBE on a stable dose of DEX. Initially, DEX dose was decreased by 50% over a 2-week period and then held at this level for 3 weeks. The primary end point was the proportion of patients who responded to treatment—patients who achieved a ≥ 50% DEX reduction from baseline and achieved stable or improved neurologic examination score and Karnofsky performance score at week 2, and then continued to respond at week 5.

Results

One hundred patients received subcutaneous injections of 1 mg twice per day of CrA and 100 patients received placebo for the duration of the study period. Although results did not attain statistical significance (at the P < .05 level), a clinically important difference in the proportion of responders between the CrA group (57.0%) and the placebo group (46.0%; P = .12) was observed. In addition, the maximum percent reduction in DEX dose achieved during the double-blind 12-week study was significantly greater in the CrA group (62.7%) than in placebo group (51.4%; P < .001). Patients receiving CrA demonstrated an improvement in myopathy and were less likely to develop signs of Cushing syndrome.

Conclusion

CrA enables a reduction in steroid requirement for patients with PBE and is associated with a reduction in the incidence and severity of common steroid adverse effects, including myopathy.
The SO2Allowance Trading System: The Ironic History of a Grand Policy Experiment
Authors: Schmalensee Richard , Stavins Robert N
Published: February 2013

Two decades have passed since the Clean Air Act Amendments of 1990 launched a grand experiment in market-based environmental policy: the SO2cap-and-trade system. That system performed well but created four striking ironies: First, by creating this system to reduce SO2emissions to curb acid rain, the government did the right thing for the wrong reason. Second, a substantial source of this system's cost-effectiveness was an unanticipated consequence of earlier railroad deregulation. Third, it is ironic that cap-and-trade has come to be demonized by conservative politicians in recent years, as this market-based, cost-effective policy innovation was initially championed and implemented by Republican administrations. Fourth, court decisions and subsequent regulatory responses have led to the collapse of the SO2market, demonstrating that what the government gives, the government can take away.
Thirty Years of Prospect Theory in Economics: A Review and Assessment
Authors: Barberis Nicholas C
Published: February 2013

In 1979, Daniel Kahneman and Amos Tversky, published a paper in Econometrica titled “Prospect Theory: An Analysis of Decision under Risk.” The paper presented a new model of risk attitudes called “prospect theory,” which elegantly captured the experimental evidence on risk taking, including the documented violations of expected utility. More than 30 years later, prospect theory is still widely viewed as the best available description of how people evaluate risk in experimental settings. However, there are still relatively few well-known and broadly accepted applications of prospect theory in economics. One might be tempted to conclude that, even if prospect theory is an excellent description of behavior in experimental settings, it is less relevant outside the laboratory. In my view, this lesson would be incorrect. Over the past decade, researchers in the field of behavioral economics have put a lot of thought into how prospect theory should be applied in economic settings. This effort is bearing fruit. A significant body of theoretical work now incorporates the ideas in prospect theory into more traditional models of economic behavior, and a growing body of empirical work tests the predictions of these new theories. I am optimistic that some insights of prospect theory will eventually find a permanent and significant place in mainstream economic analysis.
Synthesis and Characterization of Beta/MCM-41 Composite Zeolite and its Performance for n-Butane Adsorption
Authors: Ma Xiaodong , Li Zhipeng , Shen Dongmei , Cao Xiaokai , Ouyang Feng
Published: February 2013

A series of beta/MCM-41 composites with different molar ratios of microporous template agent (tetraethylammonium hydroxide or TEAOH) to mesoporous template agent (cetyltrimethylammonium bromide or CTAB) was synthesized using a two-step method. Results of X-ray powder diffraction, scanning electron microscopy and N2 adsorption confirmed that a proper molar ratio of TEAOH to CTAB benefit the formation of composite structures. The measurements of adsorption of n-butane onto the as-synthesized composites were performed at 308 K. All the experimental data fitted well with the Langmuir model. The results of n-butane adsorption demonstrated that the specific surface area and micropore volume played important roles in determining the adsorption capacity of the composites. The isosteric heat of n-butane adsorption at different coverage was also calculated using Clausius–Clapeyron equation.
Factors Affecting Ventilation and Acoustical Quality in a Sustainably-Designed and in Conventional Buildings — A Pilot Study
Authors: Hodgson Murray , Khaleghi Alireza
Published: February 2013

This paper discusses a pilot study involving direct monitoring of airflow and acoustical quality in a sustainably-designed and in conventional buildings. The objectives were to measure these environmental aspects, determine the factors affecting them and the relationships between them and key building-design concepts, and consider the implications of the results for ventilation-system design. Selected rooms in buildings with natural and mechanical ventilation, without and with acoustical treatment, were monitored. Measurements were made of airflow rates and acoustical quality. Correlations between these environmental aspects, the types of building and ventilation system, and the building window status were investigated. In rooms with natural ventilation, noise levels were lower; however, the rooms had lower airflow rates. Rooms with mechanical ventilation had higher airflow rates, but noise levels were higher; HVAC noise was a problem if the system was not well designed. In naturally-ventilated buildings, airflow rates and noise levels were low with windows closed, but opening the windows to increase the airflow rate resulted in higher noise levels. The results of the study suggest that the acceptability of indoor environments in buildings depends on the degree of compliance of the design and its implementation with standards and design guidelines, whether the original design is ‘sustainable’ or not.
The Contributions of John M. Seiner towards Aeroacoustic Facilities and Experimental Techniques
Authors: Jansen Bernard J.
Published: February 2013

John M. “Jack” Seiner leaves behind a legacy of contributions to the science of Aeroacoustics. This memorial article concentrates on his contributions to the facilities and instrumentation he conceived, developed, and utilized to forward our understanding of jet noise, supersonic flows, and related acoustic issues. From his earliest days at NASA Langley Research Center in 1974, Jack worked to understand the physics of the problems he studied and strove to correctly model the physics of the problem at hand correctly in the laboratory. For jet noise research, this drove the requirement that the facility had to provide heated air to the model nozzle. Jack believed in the future of computational fluid dynamics and supported the development of codes to calculate shock containing jets and later advancements. When a facility capability or experimental technique did not exist to answer his questions, he worked to secure funding and develop these capabilities and techniques to demonstrate their value to aeroacoustic research. He was a pioneer in the study of twin-plume resonance and using propane fueled burners to achieve realistic jet plume conditions in the laboratory.
The Prediction of Broadband Shock-Associated Noise Including Propagation Effects
Authors: Miller Steven A. E. , Morris Philip J.
Published: February 2013

An acoustic analogy is developed based on the Euler equations for broadband shock-associated noise (BBSAN) that directly incorporates the vector Green's function of the linearized Euler equations and a steady Reynolds-Averaged Navier-Stokes solution (SRANS) to describe the mean flow. The vector Green's function allows the BBSAN propagation through the jet shear layer to be determined. The large-scale coherent turbulence is modeled by two-point second order velocity cross-correlations. Turbulent length and time scales are related to the turbulent kinetic energy and dissipation rate. An adjoint vector Green's function solver is implemented to determine the vector Green's function based on a locally parallel mean flow at different streamwise locations. The newly developed acoustic analogy can be simplified to one that uses the Green's function associated with the Helmholtz equation, which is consistent with a previous formulation by the authors. A large number of predictions are generated using three different nozzles over a wide range of fully-expanded jet Mach numbers and jet stagnation temperatures. These predictions are compared with experimental data from multiple jet noise experimental facilities. In addition, two models for the so-called ‘fine-scale’ mixing noise are included in the comparisons. Improved BBSAN predictions are obtained relative to other models that do not include propagation effects.
Numerical Investigation of 3-D Supersonic Jet Flows Using Large-Eddy Simulation
Authors: Lo S.-C. , Aikens K. M. , Blaisdell G. A. , Lyrintzis A. S.
Published: February 2013

The farfield noise generated by supersonic jets is investigated by a computational aeroacoustics methodology that couples 3-D large-eddy simulation (LES) near field data with the Ffowcs Williams- Hawkings method for farfield noise prediction. In order to accurately simulate jets at off-design supersonic conditions, we employ LES with characteristic filters for shock-capturing. This approach limits the dissipation of noise-producing turbulent fluctuations, and is suitable for incorporation into existing solvers. To further limit dissipation, a shock detector is used to determine shock locations and characteristic filters are applied locally. In this study, both perfectly-expanded and under-expanded unheated jets are investigated, with and without using characteristic filters. Comparisons with similar numerical and experimental data show reasonable agreement of the jet mean flow, turbulent statistics, and acoustics results. Preliminary grid-refinement shows improvement in these results.
Sand-Dust Storm Simulation Model Coupled with PSU/NCAR Mesoscale Model
Authors: Jiang J.R. , Zhang X.Y. , Zhou C.H. , Liu H.L. , Chi X.B.
Published: February 2013

A sand-dust numerical model coupled with MM5(PSU/NCAR mesoscale model) –CUCSDust (CMA Unified Chemistry System-Dust) is introduced. CUCSDust includes such detail physical processes as dust production, transport, growth, coagulation, dry and wet deposition, which can simulate and forecast the initial and sand-dust concentration of sand and dust storm. A parallel scheme is also designed to reduce the run-time which is most important for real-time forecasting. Based on CUCSDust, a numerical model forecasting system is established in northeast Asia, and is applied to China Meteorological Administration (CMA) for operational prediction of sand and dust storm from March, 2006. A prediction result of severe sand and dust storm occurred in 26–28, March, 2006 is chosen, which shows no difference for sand-dust spatial distribution between model outputs and remote sensing monitoring imagers and indicates that the model system has the capability of real-time forecasting sand and dust storm in northeast Asia.*
An Effective Approach to Integrated Learning in Capstone Design
Authors: Hackman Steven , Sokol Joel , Zhou Chen
Published: February 2013

The H. Milton Stewart School of Industrial and Systems Engineering (ISyE) at Georgia Tech has developed an integrated approach to its capstone Senior Design course in which students form teams and identify, scope, and execute projects for real-world clients. Historically, the course has focused mainly on the engineering challenges of industry projects, but the skill set required of new industrial engineering and operations research practitioners is much broader. The new course structure creatively integrates internal and external resources for teaching business skills, soft skills, professionalism, and legal issues in an interdisciplinary, on-demand team-teaching format. Assessments show that student preparation has increased, especially in nontechnical areas. In addition, project quality has dramatically improved and is much more consistent. Both an external review board and the most recent ABET review cited the new Senior Design course as one of ISyE's strengths.
Center for Productivity Innovation's Student Project with Industry Program at the University of Tennessee, Department of Industrial and Systems Engineering
Authors: Sawhney Rapinder , Maleki Sima , Wilck Joseph , Hashemian Pedraum
Published: February 2013

A robust graduate engineering education experience requires students to learn the fundamental subject knowledge, to develop their ability to apply what they know to actual projects, and to contribute to the current body of knowledge by writing theses or dissertations. At the University of Tennessee, Knoxville, Industrial and Systems Engineering students have an opportunity, in the Student Projects with Industry (SPI) program within the Center for Productivity Innovation, to develop their research ideas in conjunction with industry. The success of the SPI program is assessed by evaluating the impact of the SPI program on the preparation of the students, the academic welfare of the department, and the program's economic and social impact on the community. The SPI program provides students with simulated work experiences that enhance their leadership attributes, developing students' critical thinking capabilities, and improving their technical, organizational, and social skills. That these skills enhance students' success both in the university and in their careers is evident in measurable results, including higher student graduation rates, an increased number of publications, and a wider sponsor network for potential funding. The impact can further be measured by the millions of dollars affecting the local economy, in addition to the intangible social benefits gained.
Probe-Based Quantitative PCR Assay for Detecting Constitutional and Somatic Deletions in the NF1 Gene: Application to Genetic Testing and Tumor Analysis
Authors: Terribas Ernest , Garcia-Linares Carles , Lázaro Conxi , Serra Eduard
Published: February 2013

BACKGROUND

About 5% of patients with neurofibromatosis type 1 (NF1) bear constitutional microdeletions that encompass NF1 (neurofibromin 1) and neighboring genes. These patients are characterized by the development of a high number of dermal neurofibromas (dNFs), mental retardation, and an increased risk of developing a malignant peripheral nerve sheath tumor (MPNST). Additionally, 10% of somatic second hits identified in dNFs are caused by deletions involving the NF1 gene. To detect constitutional and somatic deletions, we developed a probe-based quantitative PCR (qPCR) assay for interrogating the copy number status of 11 loci distributed along a 2.8-Mb region around the NF1 gene.

METHODS

We developed the qPCR assay with Universal ProbeLibrary technology (Roche) and designed a Microsoft Excel spreadsheet to analyze qPCR data for copy number calculations. The assay fulfilled the essential aspects of the MIQE (minimum information for publication of quantitative real-time PCR experiments) guidelines and used the qBase relative quantification framework for calculations.

RESULTS

The assay was validated with a set of DNA samples with known constitutional or somatic NF1 deletions. The assay showed high diagnostic sensitivity and specificity and distinguished between Type-1, Type-2, and atypical constitutional microdeletions in 14 different samples. It also identified 16 different somatic deletions in dNFs. These results were confirmed by multiplex ligation-dependent probe amplification.

CONCLUSIONS

The qPCR assay provides a methodology for detecting constitutional NF1 microdeletions that could be incorporated as an additional technique in a genetic-testing setting. It also permits the identification of somatic NF1 deletions in tissues with a high percentage of cells bearing 2 copies of the NF1 gene.
Estimating time-dependent transmission rate of avian influenza via stable numerical algorithm
Authors: Smirnova Alexandra , Tuncer Necibe
Published: February 2013

One of the main challenges in mathematical modeling of infectious diseases is to estimate the model parameters realistically. It is crucial to have accurate parameters in order to analyze the control strategies and to predict the outcome of the disease.
In particular, the transmission rate of infectious diseases is very difficult to estimate. In this paper, we propose a numerical algorithm for estimating the transmission rate of avian influenza. We address the question of calculating the time-dependent bird-to-human transmission rate of the disease using cumulative
number of infected H5N1 human cases and the number of infected poultry. A new regularization algorithm for solving this problem numerically is proposed. Theoretical analysis of the inversion procedure is accompanied by numerical experiments on simulated and real data. The qualitative and quantitative study of the computed solutions indicates that for real data, our numerical results capture a number of important properties that the highly pathogenic avian influenza (HPAI) transmission rate does, indeed, exhibit. The simulation study shows that the method introduced in this paper performs satisfactorily.
A new cumulative wavefront reconstructor for the Shack–Hartmann sensor
Authors: Neubauer Andreas
Published: February 2013

We present a new direct algorithm for the reconstruction of the optical
wavefront from the Shack–Hartmann sensor measurements in Single Conjugate
Adaptive Optics (SCAO) systems. The computational complexity of this method
which is based on linear triangular finite elements is linear in the number of
unknowns. Moreover, due to its simple structure, the cumulative reconstructor is
pipelinable and parallelizable, which makes the effective computation even
faster. Error estimates are given in dependence of the number of the
subapertures and the data noise.
PLA/PLGA nanoparticles for delivery of drugs across the blood-brain barrier
Authors: Li Jingyan , Sabliov Cristina
Published: February 2013

The blood-brain barrier (BBB), which protects the central nervous system (CNS) from unnecessary substances, is a challenging obstacle in the treatment of CNS disease. Many therapeutic agents such as hydrophilic and macromolecular drugs cannot overcome the BBB. One promising solution is the employment of polymeric nanoparticles (NPs) such as poly (lactic-co-glycolic acid) (PLGA) NPs as drug carrier. Over the past few years, significant breakthroughs have been made in developing suitable PLGA and poly (lactic acid) (PLA) NPs for drug delivery across the BBB. Recent advances on PLGA/PLA NPs enhanced neural delivery of drugs are reviewed in this paper. Both in vitro and in vivo studies are included. In these papers, enhanced cellular uptake and therapeutic efficacy of drugs delivered with modified PLGA/PLA NPs compared with free drugs or drugs delivered by unmodified PLGA/PLA NPs were shown; no significant in vitro cytotoxicity was observed for PLGA/PLA NPs. Surface modification of PLGA/PLA NPs by coating with surfactants/polymers or covalently conjugating the NPs with targeting ligands has been confirmed to enhance drug delivery across the BBB. Most unmodified PLGA NPs showed low brain uptake (<1%), which indirectly confirms the safety of PLGA/PLA NPs used for other purposes than treating CNS diseases.
Multiple Dependent State Sampling Plan Based on Process Capability Index
Authors: Aslam Muhammad , Azam Muhammad , Jun Chi-Hyuck
Published: February 2013

This paper extends the idea of multiple dependent state sampling plans to the case of using process capability index when the quality characteristic of the product follows the normal distribution. The plan parameters are determined using the optimization process with minimum values of sample size so that the specified producer’s risk and consumer’s risk should be satisfied simultaneously for given values of acceptable quality level and limiting quality level in terms of fraction defective beyond two specification limits. The plan parameters are determined under symmetric and asymmetric cases of fraction defective. The advantage of the proposed plan is discussed over the single variable sampling plan. A real example is presented to illustrate the proposed plan in practice.
Apparatus for Geosynthetic Interface Testing and Evaluation Under Elevated Temperature Conditions
Authors: Karademir Tanay , Frost J. David
Published: February 2013

Temperature is one of many important environmental variables that can impact the long-term performance, strength, and deformation characteristics of many man-made construction materials, including geosynthetics. The functional engineering properties of these materials must remain within acceptable limits during their service life to ensure that the overall design and performance are acceptable. In the case of geosynthetics used in landfills and other applications, laboratory interface shear tests are performed under standard test conditions, including temperature. Information emerging today shows that geosynthetic interfaces (i.e., in landfill liner applications) experience elevated temperatures resulting from exothermic reactions occurring in the waste body, amongst other factors. To this end, the field conditions at elevated temperatures should also be simulated in the laboratory during physical/mechanical laboratory tests in order for researchers to better understand in situ functional engineering properties and operational performance of manmade geo-construction materials. For this purpose, a temperature-controlled chamber was designed and developed to allow the shear behavior of geosynthetic–geosynthetic and soil–geosynthetic interfaces to be evaluated at different temperatures. This paper describes both the development and the validation of the test system. The results of experimental investigations are presented to illustrate how the shear behavior of interfaces between nonwoven polypropylene geotextile and smooth and/or textured high density polyethylene geomembrane, as well as those between rounded and/or angular sand and geomembranes, change with temperature. The results provide insight into the importance of being able to independently control this variable during mechanical testing in the laboratory.