bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of a scalable process for high‐yield lentiviral vector production by transient transfection of HEK293 suspension cultures
Authors: Ansorge Sven , Lanthier Stéphane , Transfiguracion Julia , Durocher Yves , Henry Olivier , Kamen Amine 
Published: July 2009

AbstractBackgroundLentiviral vectors (LV) offer several advantages over other gene delivery vectors. Their potential for the integration and long‐term expression of therapeutic genes renders them an interesting tool for gene and cell therapy interventions. However, large‐scale LV production remains an important challenge for the translation of LV‐based therapeutic strategies to the clinic. The development of robust processes for mass production of LV is needed.MethodsA suspension‐grown HEK293 cell line was exploited for the production of green fluorescent protein‐expressing LV by transient polyethylenimine (PEI)‐based transfection with LV‐encoding plasmid constructs. Using third‐generation packaging plasmids (Gag/Pol, Rev), a vesicular stomatitis virus G envelope and a self‐inactivating transfer vector, we employed strategies to increase volumetric and specific productivity. Functional LV titers were determined using a flow cytometry‐based gene transfer assay.ResultsA combination of the most promising conditions (increase in cell density, medium selection, reduction of PEI–DNA complexes per cell, addition of sodium butyrate) resulted in significantly increased LV titers of more than 150‐fold compared to non‐optimized small‐scale conditions, reaching infectious titers of approximately 108 transducing units/ml. These conditions are readily scalable and were validated in 3‐liter scale perfusion cultures.ConclusionsOur process produces LV in suspension cultures and is consequently easily scalable, industrially viable and generated more than 1011 total functional LV particles in a single bioreactor run. This process will allow the production of LV by transient transfection in sufficiently large quantities for phase I clinical trials at the 10–20‐liter bioreactor scale. Copyright © 2009 John Wiley & Sons, Ltd.
Impaired clearance of accumulated lysosomal glycogen in advanced Pompe disease despite high‐level vector‐mediated transgene expression
Authors: Sun Baodong , Zhang Haoyue , Bird Andrew , Li Songtao , Young Sarah P. , Koeberl Dwight D. 
Published: July 2009

AbstractBackgroundInfantile‐onset glycogen storage disease type II (GSD‐II; Pompe disease; MIM 232300) causes death early in childhood from cardiorespiratory failure in the absence of effective treatment, whereas late‐onset Pompe disease causes a progressive skeletal myopathy. The limitations of enzyme replacement therapy could potentially be addressed with adeno‐associated virus (AAV) vector‐mediated gene therapy.MethodsAAV vectors containing tissue‐specific regulatory cassettes, either liver‐specific or muscle‐specific, were administered to 12‐ and 17‐month‐old Pompe disease mice to evaluate the efficacy of gene therapy in advanced Pompe disease. Biochemical correction was evaluated through acid α‐glucosidase (GAA) activity and glycogen content analyses of the heart and skeletal muscle. Western blotting, urinary biomarker, and Rotarod performance were evaluated after vector administration.ResultsThe AAV vector containing the liver‐specific regulatory cassette secreted high‐level human GAA into the blood and corrected glycogen storage in the heart and diaphragm. The biochemical correction of the heart and diaphragm was associated with efficacy, as reflected by increased Rotarod performance; however, the clearance of glycogen from skeletal muscles was relatively impaired compared to in younger Pompe disease mice. An alternative vector containing a muscle‐specific regulatory cassette transduced skeletal muscle with high efficiency, but also failed to achieve complete clearance of accumulated glycogen. Decreased transduction of the heart and liver in older mice, especially in females, was implicated as a cause for reduced efficacy in advanced Pompe disease.ConclusionsThe impaired efficacy of AAV vector‐mediated gene therapy in old Pompe disease mice emphasizes the need for early treatment to achieve full efficacy. Copyright © 2009 John Wiley & Sons, Ltd.
Anisakis simplex allergens remain active after conventional or microwave heating and pepsin treatments of chilled and frozen L3 larvae
Authors: Vidaček Sanja , de las Heras Cristina , Solas Maria Teresa , Mendizábal Angel , Rodriguez‐Mahillo Ana I , González‐Muñoz Miguel , Tejada Margarita 
Published: July 2009

AbstractBACKGROUND: Some Anisakis simplex allergens, Ani s 4 among them, are reported to be resistant to freezing, heat and pepsin. However, the effect of conventional and microwave heating on live and frozen larvae, common conditions for fish preparation, and consecutive pepsin treatment have not been studied previously. In this study, live and frozen/thawed A. simplex larvae were subjected to conventional or microwave heating during time–temperature sufficient to kill live larvae, and digested with pepsin in the strong conditions used in fish inspection. The antigenicity of A. simplex in the larvae extracts and in the incubation media filtrates after all treatments was studied.RESULTS: The immunoblotting assay showed the presence of Ani s 4 in all the larvae extracts and all the incubation media filtrates. A. simplex crude antigens were detected in all conditions; nevertheless, differences were observed among treatments, with lower values detected in the filtrates obtained after the strong acidic pepsin treatment.CONCLUSION: The results indicate that ingestion of A. simplex larvae can cause allergy in consumers already sensitised to this allergen, even if the parasitised fish is consumed well‐cooked and after freezing in the recommended conditions selected for killing the larvae to avoid human anisakiasis. Copyright © 2009 Society of Chemical Industry
Hybrid Organic/Inorganic UV‐Cured Acrylic Films with Hydrophobic Surface Properties
Authors: Sangermano Marco , Bongiovanni Roberta , Longhin Marco , Rizza Giancarlo , Kausch Charles M. , Kim Yongsin , Thomas Richard R. 
Published: July 2009

AbstractHybrid organic/inorganic acrylic nanostructured films were prepared by a UV/thermal dual‐curing process. The role of a fluorinated hydroxyl acrylate monomer (AF) as coupling agent was investigated. Increased Tg values and modulus of the dual‐cured films were achieved by increasing the TEOS inorganic precursor. The coupling agent deeply modified the surface properties of the cured films: the formation of hybrid films characterized by high hydrophobicity together with an increase on surface hardness was achieved. TEM analysis clearly evidenced the reducing of the nanosize dimensions of the inorganic silica domains by increasing the coupling agent content in the photocurable formulation.magnified image
Verarbeitung hochfester Aluminiumlegierungen durch umformende Verfahren
Authors: Neugebauer R. , Lachmann L. , Grübler R. 
Published: July 2009

AbstractBasierend auf experimentell ermittelten Werkstoffkennwerten wird ein Vergleich des Umformverhaltens der beiden Aluminiumlegierungen im Anlieferungszustand (EN AW‐7075 T651) sowie im modifizierten Zustand (EN AW‐7075 ECAP) bei der Verarbeitung mit herkömmlichen Umformverfahren (Walzen, Fließpressen) angestellt. Zudem werden die Verfahrensgrenzen des Umformgrades durch Variation der Werkzeuggeometrien experimentell lokalisiert. Dabei ist ebenfalls Untersuchungsgegenstand, den Einfluss des Verfahrens auf das Umformvermögen zu ermitteln. Davon ausgehend werden Werkzeugkonzepte entwickelt, die eine Umformung des hochfesten Aluminiums unter Erzeugung von hydrostatischen Druckzuständen in der Umformzone ermöglichen. Sowohl die Simulation als auch die Versuche zeigten Materialversagen der ultrafeinkörnigen Werkstoffe beim Fließpressen. Das Walzen als inkrementelles Umformverfahren ermöglichte hingegen eine schadensfreie Herstellung der Werkstücke.
VEGF expression as a prognostic marker in osteosarcoma
Authors: Bajpai Jyoti , Sharma Meharchand , Sreenivas Vishnubhatla , Kumar Rakesh , Gamnagatti Shivanand , Khan Shah Alam , Rastogi Shishir , Malhotra Arun , Bakhshi Sameer 
Published: July 2009

AbstractBackgroundThe vascular endothelial growth factor (VEGF) pathway is the key regulator of angiogenesis. In osteosarcoma baseline VEGF is of proven prognostic value but prognostic potential of post‐NACT VEGF expression is largely unexplored.ProcedureTreatment naive patients with osteosarcoma were subjected to initial staging workup followed by three cycles of neoadjuvant chemotherapy (NACT) and surgery; resected tumors were assessed for histological necrosis by Huvos grading. Initial biopsy and resected tumor specimens post‐NACT were examined for VEGF expression by immunohistochemistry. Positive VEGF expression was considered when intensive positive staining was observed in >10% of the tumor cells. VEGF expression at baseline was compared with grade of tumor; pre‐NACT and post‐NACT VEGF expression were compared with histological necrosis. Receiver operating characteristic curves were generated to assess best threshold and predictability.ResultsA total of 31 patients were recruited with median age of 17 years (range 5–66 years); male/female ratio was 25:6; 23 patients (74%) were non‐metastatic. At baseline, there was 90% concordance between positive VEGF expression and higher histological grade (28/31); baseline VEGF expression did not correlate well with stage and histological necrosis. Twenty‐one (67%) were poor and 10 (33%) were good histologic responders; post‐NACT VEGF expression as well as VEGF change following NACT significantly correlated with histological necrosis.ConclusionPositive VEGF expression in surviving tumor cells post‐NACT in resected tumors appears to be an important negative prognostic factor in osteosarcoma which may help future therapies to be identified according to the angiogenic potential of the disease. Pediatr Blood Cancer 2009;53:1035–1039. © 2009 Wiley‐Liss, Inc.
Spontaneous reporting of adverse drug events by Korean regional pharmacovigilance centers
Authors: Shin Yoo Seob , Lee Yong‐Won , Choi Young Hwa , Park Byungjoo , Jee Young Koo , Choi Sung‐Kyu , Kim Eung‐Gyu , Park Jung‐Won , Hong Chein‐Soo 
Published: July 2009

AbstractPurposePatterns of prescriptions are markedly influenced by regional disease entities, medical education, culture, economic status, and available pharmaceutical companies. Features of adverse drug reactions (ADRs) may vary in different countries. In this study, we analyzed the causative drugs and clinical manifestations of spontaneously reported ADRs in Korea.MethodsSix Korean Regional Pharmacovigilance Centers collected 1418 cases of spontaneously reported adverse drug events (ADEs) by doctors, pharmacists, and nurses, and the clinical features and causative drugs were evaluated. The data were collected from general hospitals (76.5%), primary clinics, and pharmacies (23.5%).ResultsBased upon the World Health Organization (WHO)‐Uppsala Monitoring Center criteria (certain—13.7%, probable—46.1%, possible—32.1%), 91.9% of the collected events were suspected to be ADRs and 15.8% of patients experienced serious ADRs. The most prevalent causative drugs were antibiotics (31.6%), followed by contrast dyes (14.0%), non‐steroidal anti‐inflammatory drugs (NSAIDs) (11.1%), anti‐psychotics (5.4%), anti‐convulsants (5.2%), cardiovascular agents (4.8%), anti‐neoplastics (4.6%), and opiates and non‐opiate pain killers (3.5%). Among the antibiotics, cephalosporins (8.1%) were the most common, followed by anti‐tuberculosis agents (5.7%), quinolones (4.0%), vancomycin (3.1%), and penicillin (2.8%). The most common side effect was skin manifestations, which were seen in 42% of the patients, followed by neurologic manifestations (14%), gastrointestinal involvements (12.9%), generalized reactions (9.4%), and respiratory involvements (4.5%).ConclusionAntibiotics, contrast dyes, and NSAIDs were the most common causative drugs for ADRs, which reflects the prescription pattern and the prevalence of diseases in Korea. These data may be useful in establishing a Korean pharmacovigilance system. Copyright © 2009 John Wiley & Sons, Ltd.
Obesity rates in special populations of children and potential interventions
Authors: Holcomb Matthew J. , Pufpaff Lisa A. , McIntosh David E. 
Published: July 2009

AbstractChildhood obesity has become a problem of epidemic proportions in the United States, but much of the research has focused on prevention and intervention programs, which target the general population of school children. Overlooked in the literature are children with special needs (including autism, genetic disorders, Down syndrome, and Prader‐Willi syndrome), who on average have higher rates of obesity than do their typically functioning peers. Specifically, some clinical populations of children have genetic predispositions that make intervention more difficult to accomplish. General intervention considerations are discussed and applied to these groups of children. © 2009 Wiley Periodicals, Inc.
A probability model of system downtime with implications for optimal warranty design
Authors: Flood Ben , Houlding Brett , Wilson Simon P. , Vilkomir Sergiy 
Published: July 2009

AbstractTraditional approaches toward modeling the availability of a system often do not formally take into account uncertainty over the parameter values of the model. Such models are then frequently criticized because the observed reliability of a system does not match that predicted by the model. This paper extends a recently published segregated failures model so that, rather than providing a single figure for the availability of a system, uncertainty over model parameter values is incorporated and a predictive probability distribution is given. This predictive distribution is generated in a practical way by displaying the uncertainties and dependencies of the parameters of the model through a Bayesian network (BN). Permitting uncertainty in the reliability model then allows the user to determine whether the predicted reliability was incorrect due to inherent variability in the system under study, or due to the use of an inappropriate model. Furthermore, it is demonstrated how the predictive distribution can be used when reliability predictions are employed within a formal decision‐theoretic framework. Use of the model is illustrated with the example of a high‐availability computer system with multiple recovery procedures. An BN is produced to display the relations between parameters of the model in this case and to generate a predictive probability distribution of the system's availability. This predictive distribution is then used to make two decisions under uncertainty concerning the offered warranty policies on the system: a qualitative decision and an optimization over a continuous decision space. Copyright © 2009 John Wiley & Sons, Ltd.
Networked estimation under contention‐based medium access
Authors: Rabi Maben , Stabellini Luca , Proutiere Alexandre , Johansson Mikael 
Published: July 2009

AbstractThis paper studies networked estimation over a communication channel shared by a contention‐based medium access protocol. A collection ofNidentical and physically decoupled scalar systems are sampled without sensor noise and transmitted over a common channel, using a contention‐based medium access mechanism. We first carry out a calculation of the average distortion in estimation with irregular samples. Given the rate of packet generation at sensors, we characterize the traffic characteristics of the some contention‐based MAC schemes. This lets us derive the statistics of inter‐arrival times which in turn allows us to compute the packet loss rates and also the statistics of delay within a sample period. Using these results, we track the estimation performance as the sample generation rate and the number of contending nodes are varied. We provide a heuristic rule‐of‐thumb for choosing the sampling interval which minimizes the average distortion. By combining the network traffic characterization with that of the estimation performance, we show this rule performs pretty well. Carrying along the same lines, we are able to compute the scaling limits of estimation performance with respect to the number of contending nodes. Copyright © 2009 John Wiley & Sons, Ltd.
Estimating incubation period distributions with coarse data
Authors: Reich Nicholas G. , Lessler Justin , Cummings Derek A. T. , Brookmeyer Ron 
Published: July 2009

AbstractThe incubation period, the time between infection and disease onset, is important in the surveillance and control of infectious diseases but is often coarsely observed. Coarse data arises because the time of infection, the time of disease onset or both are not known precisely. Accurate estimates of an incubation period distribution are useful in real‐time outbreak investigations and in modeling public health interventions. We compare two methods of estimating such distributions. The first method represents the data as doubly interval‐censored. The second introduces a data reduction technique that makes the computation more tractable. In a simulation study, the methods perform similarly when estimating the median, but the first method yields more reliable estimates of the distributional tails. We conduct a sensitivity analysis of the two methods to violations of model assumption and we apply these methods to historical incubation period data on influenza A and respiratory syncytial virus. The analysis of reduced data is less computationally intensive and performs well for estimating the median under a wide range of conditions. However for estimation of the tails of the distribution, the doubly interval‐censored analysis is the recommended procedure. Copyright © 2009 John Wiley & Sons, Ltd.
Some statistics in bioinformatics: The fifth Armitage Lecture
Authors: Solomon Patricia J. 
Published: July 2009

AbstractThe spirit and content of the 2007 Armitage Lecture are presented in this paper. To begin, two areas of Peter Armitage's early work are distinguished: his pioneering research on sequential methods intended for use in medical trials and the comparison of survival curves. Their influence on much later work is highlighted, and motivate the proposal of several statistical ‘truths’ that are presented in the paper. The illustration of these truths demonstrates biology's new morphology and its dominance over statistics in this century. An overview of a recent proteomics ovarian cancer study is given as a warning of what can happen when bioinformatics meets epidemiology badly, in particular, when the study design is poor. A statistical bioinformatics success story is outlined, in which gene profiling is helping to identify novel genes and networks involved in mouse embryonic stem cell development. Some concluding thoughts are given. Copyright © 2009 John Wiley & Sons, Ltd.
What works for whom? Gender differences in intake characteristics and treatment outcomes following Multisystemic Therapy
Authors: Ogden Terje , Amlund Hagen Kristine 
Published: July 2009

ABSTRACTAims of the studyWe investigated whether girls and boys had similar referral symptoms and background characteristics at intake to Multisystemic Therapy (MST) and whether adolescent girls with serious behavior problems benefited as much from MST treatment as did boys. We also examined gender differences in rate of co‐morbidity at intake and whether the families of boys and girls referred to MST differed in their evaluation of the treatment received.MethodParticipants were 117 Norwegian adolescent girls (35%) and boys (65%), ranging in age from 12 to 17 (M = 14.58), referred to MST treatment in the first and second year of the program operation.ResultsGender differences appeared for some referral reasons, intake characteristics and treatment changes, but the similarities between girls and boys far outnumbered their differences.ConclusionsAlthough girls may present a somewhat different problem profile than do boys and their risk factors for developing conduct problems may be somewhat different, MST seemed flexible and robust enough to be effective for most adolescents in the present sample, regardless of gender.
A Controller for a Light Source
Authors: Bailey S. W. , McCabe J. B. 
Published: July 2009

An instrument is described that will brighten and dim a light source and control its “on” and “off” timing.The periods of brightening and dimming and the period of full illumination are both adjustable.The instrument is being used successfully for studying the effects of changing light intensity and photoperiod on the activity and development of insects.
Olfactory Stimulation of Tsetse Flies and Blowflies
Authors: Hughes J. C. 
Published: July 2009

An apparatus for exposing insects to known concentrations of vapours from odorous liquids is described; it was used in a laboratory in England to test adult tsetse flies, Glossina palpalis (R.-D.) and G. morsitans Westw., obtained from Africa as pupae, and the blowfly, Phormia terraenovae R.-D. There is a definite pattern of behaviour of the flies in olfactory stimulants, in the final phase of which they are excited to fly. The number of seconds for which a fly is in flight gives a measure of its activation by the vapour. The method gives results comparable with those obtained with a standard choice-chamber technique and has considerable practical advantages for work with tsetse flies. The effects of concentrations of vapour, period of exposure, condition of the flies and external conditions on the response of tsetse flies to vapours were studied.The response of G. morsitans and P. terraenovae to a selection of aliphatic acids, alcohols, esters and amines was determined, using a standardised procedure. There is a marked similarity between the two species in the concentrations of vapours required to activate them. The standard molar concentration, defined as the concentration of vapour required to raise the activity of the flies to a standard level of ten times that in pure air, was calculated for each compound tested from the regression of activity on concentration. Threshold concentrations (the highest concentrations that failed to raise fly-activity) were also calculated from the regression equations.
The Resting Sites of Glossina swynnertoni Aust. in the Wet Season
Authors: Isherwood F. 
Published: July 2009

The biased nature of the catches of Glossina swynnertoni Aust. made on fly-rounds at Shinyanga, Tanganyika Territory, which show an unduly low proportion of females, nearly all of which are hungry, and lack of knowledge of the fly's habits when inactive, has led to a search for resting flies.Previous recorded observations on resting tsetse flies are briefly reviewed. These show that the resting sites chosen differ according to species and even within a species. Differences of the second kind probably reflect seasonal changes.