Biphasic and monophasic repair: comparative implications for biologically equivalent dose calculations in pulsed dose rate brachytherapy of cervical carcinoma

PubMed Central

Millar, W T; Davidson, S E

2013-01-01

Objective: To consider the implications of the use of biphasic rather than monophasic repair in calculations of biologically-equivalent doses for pulsed-dose-rate brachytherapy of cervix carcinoma. Methods: Calculations are presented of pulsed-dose-rate (PDR) doses equivalent to former low-dose-rate (LDR) doses, using biphasic vs monophasic repair kinetics, both for cervical carcinoma and for the organ at risk (OAR), namely the rectum. The linear-quadratic modelling calculations included effects due to varying the dose per PDR cycle, the dose reduction factor for the OAR compared with Point A, the repair kinetics and the source strength. Results: When using the recommended 1 Gy per hourly PDR cycle, different LDR-equivalent PDR rectal doses were calculated depending on the choice of monophasic or biphasic repair kinetics pertaining to the rodent central nervous and skin systems. These differences virtually disappeared when the dose per hourly cycle was increased to 1.7 Gy. This made the LDR-equivalent PDR doses more robust and independent of the choice of repair kinetics and α/β ratios as a consequence of the described concept of extended equivalence. Conclusion: The use of biphasic and monophasic repair kinetics for optimised modelling of the effects on the OAR in PDR brachytherapy suggests that an optimised PDR protocol with the dose per hourly cycle nearest to 1.7 Gy could be used. Hence, the durations of the new PDR treatments would be similar to those of the former LDR treatments and not longer as currently prescribed. Advances in knowledge: Modelling calculations indicate that equivalent PDR protocols can be developed which are less dependent on the different α/β ratios and monophasic/biphasic kinetics usually attributed to normal and tumour tissues for treatment of cervical carcinoma. PMID:23934965

Computation of the effective mechanical response of biological networks accounting for large configuration changes.

PubMed

El Nady, K; Ganghoffer, J F

2016-05-01

The asymptotic homogenization technique is involved to derive the effective elastic response of biological membranes viewed as repetitive beam networks. Thereby, a systematic methodology is established, allowing the prediction of the overall mechanical properties of biological membranes in the nonlinear regime, reflecting the influence of the geometrical and mechanical micro-parameters of the network structure on the overall response of the equivalent continuum. Biomembranes networks are classified based on nodal connectivity, so that we analyze in this work 3, 4 and 6-connectivity networks, which are representative of most biological networks. The individual filaments of the network are described as undulated beams prone to entropic elasticity, with tensile moduli determined from their persistence length. The effective micropolar continuum evaluated as a continuum substitute of the biological network has a kinematics reflecting the discrete network deformation modes, involving a nodal displacement and a microrotation. The statics involves the classical Cauchy stress and internal moments encapsulated into couple stresses, which develop internal work in duality to microcurvatures reflecting local network undulations. The relative ratio of the characteristic bending length of the effective micropolar continuum to the unit cell size determines the relevant choice of the equivalent medium. In most cases, the Cauchy continuum is sufficient to model biomembranes. The peptidoglycan network may exhibit a re-entrant hexagonal configuration due to thermal or pressure fluctuations, for which micropolar effects become important. The homogenized responses are in good agreement with FE simulations performed over the whole network. The predictive nature of the employed homogenization technique allows the identification of a strain energy density of a hyperelastic model, for the purpose of performing structural calculations of the shape evolutions of biomembranes. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effect of Computer-Assisted Instruction on Secondary School Students' Achievement in Ecological Concepts

ERIC Educational Resources Information Center

Nkemdilim, Egbunonu Roseline; Okeke, Sam O. C.

2014-01-01

This study investigated the effects of computer-assisted instruction (CAI) on students' achievement in ecological concepts. Quasi-experimental design, specifically the pre-test post test non-equivalent control group design was adopted. The sample consisted of sixty-six (66) senior secondary year two (SS II) biology students, drawn from two…

Galvanic zinc-copper microparticles inhibit melanogenesis via multiple pigmentary pathways.

PubMed

Won, Yen-Kim; Lin, Connie B; Seiberg, Miri; Chen, Nannan; Hu, Yaping; Rossetti, Dianne; Saliou, Claude; Loy, Chong-Jin

2014-01-01

The endogenous electrical field of human skin plays an important role in many skin functions. However, the biological effects and mechanism of action of externally applied electrical stimulation on skin remain unclear. Recent study showed that galvanic zinc-copper microparticles produce electrical stimulation and reduce inflammatory and immune responses in intact skin, suggesting the important role of electrical stimulation in non-wounded skin. The objective of this study is to investigate the biological effect of galvanic zinc-copper microparticles on skin pigmentation. Our findings showed that galvanic zinc-copper microparticles inhibited melanogenesis in a human melanoma cell line (MNT-1), human keratinocytes and melanoma cells co-cultures, and in pigmented epidermal equivalents. Treatment of galvanic zinc-copper microparticles inhibited melanogenesis by reducing the promoter transactivation of tyrosinase and tyrosinase-related protein-1 in human melanoma cells. In a co-culture Transwell system of keratinocytes and melanoma cells, galvanic zinc-copper microparticles reduced melanin production via downregulation of endothelin-1 secretion from keratinocytes and reduced tyrosinase gene expression in melanoma cells. In addition, exposure of pigmented epidermal equivalents to galvanic zinc-copper microparticles resulted in reduced melanin deposition. In conclusion, our data demonstrated for the first time that galvanic zinc-copper microparticles reduced melanogenesis in melanoma cells and melanin deposition in pigmented epidermal equivalents by affecting multiple pigmentary pathways.

Molecular electronics in pinnae of Mimosa pudica

PubMed Central

Foster, Justin C; Markin, Vladislav S

2010-01-01

Bioelectrochemical circuits operate in all plants including the sensitive plant Mimosa pudica Linn. The activation of biologically closed circuits with voltage gated ion channels can lead to various mechanical, hydrodynamical, physiological, biochemical and biophysical responses. Here the biologically closed electrochemical circuit in pinnae of Mimosa pudica is analyzed using the charged capacitor method for electrostimulation at different voltages. Also the equivalent electrical scheme of electrical signal transduction inside the plant's pinna is evaluated. These circuits remain linear at small potentials not exceeding 0.5 V. At higher potentials the circuits become strongly non-linear pointing to the opening of ion channels in plant tissues. Changing the polarity of electrodes leads to a strong rectification effect and to different kinetics of a capacitor. These effects can be caused by a redistribution of K+, Cl−, Ca2+ and H+ ions through voltage gated ion channels. The electrical properties of Mimosa pudica were investigated and equivalent electrical circuits within the pinnae were proposed to explain the experimental data. PMID:20448476

Molecular electronics in pinnae of Mimosa pudica.

PubMed

Volkov, Alexander G; Foster, Justin C; Markin, Vladislav S

2010-07-01

Bioelectrochemical circuits operate in all plants including the sensitive plant Mimosa pudica Linn. The activation of biologically closed circuits with voltage gated ion channels can lead to various mechanical, hydrodynamical, physiological, biochemical, and biophysical responses. Here the biologically closed electrochemical circuit in pinnae of Mimosa pudica is analyzed using the charged capacitor method for electrostimulation at different voltages. Also the equivalent electrical scheme of electrical signal transduction inside the plant's pinna is evaluated. These circuits remain linear at small potentials not exceeding 0.5 V. At higher potentials the circuits become strongly non-linear pointing to the opening of ion channels in plant tissues. Changing the polarity of electrodes leads to a strong rectification effect and to different kinetics of a capacitor. These effects can be caused by a redistribution of K(+), Cl(-), Ca(2+), and H(+) ions through voltage gated ion channels. The electrical properties of Mimosa pudica were investigated and equivalent electrical circuits within the pinnae were proposed to explain the experimental data.

Physical models of biological information and adaptation.

PubMed

Stuart, C I

1985-04-07

The bio-informational equivalence asserts that biological processes reduce to processes of information transfer. In this paper, that equivalence is treated as a metaphor with deeply anthropomorphic content of a sort that resists constitutive-analytical definition, including formulation within mathematical theories of information. It is argued that continuance of the metaphor, as a quasi-theoretical perspective in biology, must entail a methodological dislocation between biological and physical science. It is proposed that a general class of functions, drawn from classical physics, can serve to eliminate the anthropomorphism. Further considerations indicate that the concept of biological adaptation is central to the general applicability of the informational idea in biology; a non-anthropomorphic treatment of adaptive phenomena is suggested in terms of variational principles.

Simulated Response of a Tissue-equivalent Proportional Counter on the Surface of Mars.

PubMed

Northum, Jeremy D; Guetersloh, Stephen B; Braby, Leslie A; Ford, John R

2015-10-01

Uncertainties persist regarding the assessment of the carcinogenic risk associated with galactic cosmic ray (GCR) exposure during a mission to Mars. The GCR spectrum peaks in the range of 300(-1) MeV n to 700 MeV n(-1) and is comprised of elemental ions from H to Ni. While Fe ions represent only 0.03% of the GCR spectrum in terms of particle abundance, they are responsible for nearly 30% of the dose equivalent in free space. Because of this, radiation biology studies focusing on understanding the biological effects of GCR exposure generally use Fe ions. Acting as a thin shield, the Martian atmosphere alters the GCR spectrum in a manner that significantly reduces the importance of Fe ions. Additionally, albedo particles emanating from the regolith complicate the radiation environment. The present study uses the Monte Carlo code FLUKA to simulate the response of a tissue-equivalent proportional counter on the surface of Mars to produce dosimetry quantities and microdosimetry distributions. The dose equivalent rate on the surface of Mars was found to be 0.18 Sv y(-1) with an average quality factor of 2.9 and a dose mean lineal energy of 18.4 keV μm(-1). Additionally, albedo neutrons were found to account for 25% of the dose equivalent. It is anticipated that these data will provide relevant starting points for use in future risk assessment and mission planning studies.

Antipsychotic dose equivalents and dose-years: a standardized method for comparing exposure to different drugs.

PubMed

Andreasen, Nancy C; Pressler, Marcus; Nopoulos, Peg; Miller, Del; Ho, Beng-Choon

2010-02-01

A standardized quantitative method for comparing dosages of different drugs is a useful tool for designing clinical trials and for examining the effects of long-term medication side effects such as tardive dyskinesia. Such a method requires establishing dose equivalents. An expert consensus group has published charts of equivalent doses for various antipsychotic medications for first- and second-generation medications. These charts were used in this study. Regression was used to compare each drug in the experts' charts to chlorpromazine and haloperidol and to create formulas for each relationship. The formulas were solved for chlorpromazine 100 mg and haloperidol 2 mg to derive new chlorpromazine and haloperidol equivalents. The formulas were incorporated into our definition of dose-years such that 100 mg/day of chlorpromazine equivalent or 2 mg/day of haloperidol equivalent taken for 1 year is equal to one dose-year. All comparisons to chlorpromazine and haloperidol were highly linear with R(2) values greater than .9. A power transformation further improved linearity. By deriving a unique formula that converts doses to chlorpromazine or haloperidol equivalents, we can compare otherwise dissimilar drugs. These equivalents can be multiplied by the time an individual has been on a given dose to derive a cumulative value measured in dose-years in the form of (chlorpromazine equivalent in mg) x (time on dose measured in years). After each dose has been converted to dose-years, the results can be summed to provide a cumulative quantitative measure of lifetime exposure. Copyright 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Biological Basis for Chemoprevention of Ovarian Cancer

DTIC Science & Technology

2005-10-01

epithelial cells treated with the progestin levonorgestrel . Progestin mediated apoptotic effects may be a major mechanism underlying the protection...epithelial ovarian cancer. Initial studies to test the progestin levonorgestrel in an avian model of ovarian cancer have been undertaken and...is receiving 0.05 mg/day Levonorgestrel equivalent (same as first chicken trial demonstrating a chemopreventive effect), and the high progestin dose

Tracing molecular dephasing in biological tissue

NASA Astrophysics Data System (ADS)

Mokim, M.; Carruba, C.; Ganikhanov, F.

2017-10-01

We demonstrate the quantitative spectroscopic characterization and imaging of biological tissue using coherent time-domain microscopy with a femtosecond resolution. We identify tissue constituents and perform dephasing time (T2) measurements of characteristic Raman active vibrations. This was shown in subcutaneous mouse fat embedded within collagen rich areas of the dermis and the muscle connective tissue. The demonstrated equivalent spectral resolution (<0.3 cm-1) is an order of magnitude better compared to commonly used frequency-domain methods for characterization of biological media. This provides with the important dimensions and parameters in biological media characterization and can become an effective tool in detecting minute changes in the bio-molecular composition and environment that is critical for molecular level diagnosis.

Application of biological effective dose (BED) to estimate the duration of symptomatic relief and repopulation dose equivalent in palliative radiotherapy and chemotherapy.

PubMed

Jones, Bleddyn; Cominos, Matilda; Dale, Roger G

2003-03-01

To investigate the potential for mathematic modeling in the assessment of symptom relief in palliative radiotherapy and cytotoxic chemotherapy. The linear quadratic model of radiation effect with the overall treatment time and the daily dose equivalent of repopulation is modified to include the regrowth time after completion of therapy. The predicted times to restore the original tumor volumes after treatment are dependent on the biological effective dose (BED) delivered and the repopulation parameter (K); it is also possible to estimate K values from analysis of palliative treatment response durations. Hypofractionated radiotherapy given at a low total dose may produce long symptom relief in slow-growing tumors because of their low alpha/beta ratios (which confer high fraction sensitivity) and their slow regrowth rates. Cancers that have high alpha/beta ratios (which confer low fraction sensitivity), and that are expected to repopulate rapidly during therapy, are predicted to have short durations of symptom control. The BED concept can be used to estimate the equivalent dose of radiotherapy that will achieve the same duration of symptom relief as palliative chemotherapy. Relatively simple radiobiologic modeling can be used to guide decision-making regarding the choice of the most appropriate palliative schedules and has important implications in the design of radiotherapy or chemotherapy clinical trials. The methods described provide a rationalization for treatment selection in a wide variety of tumors.

Biological equivalence between LDR and PDR in cervical cancer: multifactor analysis using the linear-quadratic model.

PubMed

Couto, José Guilherme; Bravo, Isabel; Pirraco, Rui

2011-09-01

The purpose of this work was the biological comparison between Low Dose Rate (LDR) and Pulsed Dose Rate (PDR) in cervical cancer regarding the discontinuation of the afterloading system used for the LDR treatments at our Institution since December 2009. In the first phase we studied the influence of the pulse dose and the pulse time in the biological equivalence between LDR and PDR treatments using the Linear Quadratic Model (LQM). In the second phase, the equivalent dose in 2 Gy/fraction (EQD(2)) for the tumor, rectum and bladder in treatments performed with both techniques was evaluated and statistically compared. All evaluated patients had stage IIB cervical cancer and were treated with External Beam Radiotherapy (EBRT) plus two Brachytherapy (BT) applications. Data were collected from 48 patients (26 patients treated with LDR and 22 patients with PDR). In the analyses of the influence of PDR parameters in the biological equivalence between LDR and PDR treatments (Phase 1), it was calculated that if the pulse dose in PDR was kept equal to the LDR dose rate, a small the-rapeutic loss was expected. If the pulse dose was decreased, the therapeutic window became larger, but a correction in the prescribed dose was necessary. In PDR schemes with 1 hour interval between pulses, the pulse time did not influence significantly the equivalent dose. In the comparison between the groups treated with LDR and PDR (Phase 2) we concluded that they were not equivalent, because in the PDR group the total EQD(2) for the tumor, rectum and bladder was smaller than in the LDR group; the LQM estimated that a correction in the prescribed dose of 6% to 10% was ne-cessary to avoid therapeutic loss. A correction in the prescribed dose was necessary; this correction should be achieved by calculating the PDR dose equivalent to the desired LDR total dose.

Biological equivalence between LDR and PDR in cervical cancer: multifactor analysis using the linear-quadratic model

PubMed Central

Bravo, Isabel; Pirraco, Rui

2011-01-01

Purpose The purpose of this work was the biological comparison between Low Dose Rate (LDR) and Pulsed Dose Rate (PDR) in cervical cancer regarding the discontinuation of the afterloading system used for the LDR treatments at our Institution since December 2009. Material and methods In the first phase we studied the influence of the pulse dose and the pulse time in the biological equivalence between LDR and PDR treatments using the Linear Quadratic Model (LQM). In the second phase, the equivalent dose in 2 Gy/fraction (EQD2) for the tumor, rectum and bladder in treatments performed with both techniques was evaluated and statistically compared. All evaluated patients had stage IIB cervical cancer and were treated with External Beam Radiotherapy (EBRT) plus two Brachytherapy (BT) applications. Data were collected from 48 patients (26 patients treated with LDR and 22 patients with PDR). Results In the analyses of the influence of PDR parameters in the biological equivalence between LDR and PDR treatments (Phase 1), it was calculated that if the pulse dose in PDR was kept equal to the LDR dose rate, a small the-rapeutic loss was expected. If the pulse dose was decreased, the therapeutic window became larger, but a correction in the prescribed dose was necessary. In PDR schemes with 1 hour interval between pulses, the pulse time did not influence significantly the equivalent dose. In the comparison between the groups treated with LDR and PDR (Phase 2) we concluded that they were not equivalent, because in the PDR group the total EQD2 for the tumor, rectum and bladder was smaller than in the LDR group; the LQM estimated that a correction in the prescribed dose of 6% to 10% was ne-cessary to avoid therapeutic loss. Conclusions A correction in the prescribed dose was necessary; this correction should be achieved by calculating the PDR dose equivalent to the desired LDR total dose. PMID:23346123

On the Rule of Mixtures for Predicting Stress-Softening and Residual Strain Effects in Biological Tissues and Biocompatible Materials

PubMed Central

Elías-Zúñiga, Alex; Baylón, Karen; Ferrer, Inés; Serenó, Lídia; Garcia-Romeu, Maria Luisa; Bagudanch, Isabel; Grabalosa, Jordi; Pérez-Recio, Tania; Martínez-Romero, Oscar; Ortega-Lara, Wendy; Elizalde, Luis Ernesto

2014-01-01

In this work, we use the rule of mixtures to develop an equivalent material model in which the total strain energy density is split into the isotropic part related to the matrix component and the anisotropic energy contribution related to the fiber effects. For the isotropic energy part, we select the amended non-Gaussian strain energy density model, while the energy fiber effects are added by considering the equivalent anisotropic volumetric fraction contribution, as well as the isotropized representation form of the eight-chain energy model that accounts for the material anisotropic effects. Furthermore, our proposed material model uses a phenomenological non-monotonous softening function that predicts stress softening effects and has an energy term, derived from the pseudo-elasticity theory, that accounts for residual strain deformations. The model’s theoretical predictions are compared with experimental data collected from human vaginal tissues, mice skin, poly(glycolide-co-caprolactone) (PGC25 3-0) and polypropylene suture materials and tracheal and brain human tissues. In all cases examined here, our equivalent material model closely follows stress-softening and residual strain effects exhibited by experimental data. PMID:28788466

On the Rule of Mixtures for Predicting Stress-Softening and Residual Strain Effects in Biological Tissues and Biocompatible Materials.

PubMed

Elías-Zúñiga, Alex; Baylón, Karen; Ferrer, Inés; Serenó, Lídia; García-Romeu, Maria Luisa; Bagudanch, Isabel; Grabalosa, Jordi; Pérez-Recio, Tania; Martínez-Romero, Oscar; Ortega-Lara, Wendy; Elizalde, Luis Ernesto

2014-01-16

In this work, we use the rule of mixtures to develop an equivalent material model in which the total strain energy density is split into the isotropic part related to the matrix component and the anisotropic energy contribution related to the fiber effects. For the isotropic energy part, we select the amended non-Gaussian strain energy density model, while the energy fiber effects are added by considering the equivalent anisotropic volumetric fraction contribution, as well as the isotropized representation form of the eight-chain energy model that accounts for the material anisotropic effects. Furthermore, our proposed material model uses a phenomenological non-monotonous softening function that predicts stress softening effects and has an energy term, derived from the pseudo-elasticity theory, that accounts for residual strain deformations. The model's theoretical predictions are compared with experimental data collected from human vaginal tissues, mice skin, poly(glycolide-co-caprolactone) (PGC25 3-0) and polypropylene suture materials and tracheal and brain human tissues. In all cases examined here, our equivalent material model closely follows stress-softening and residual strain effects exhibited by experimental data.

Automated design of genetic toggle switches with predetermined bistability.

PubMed

Chen, Shuobing; Zhang, Haoqian; Shi, Handuo; Ji, Weiyue; Feng, Jingchen; Gong, Yan; Yang, Zhenglin; Ouyang, Qi

2012-07-20

Synthetic biology aims to rationally construct biological devices with required functionalities. Methods that automate the design of genetic devices without post-hoc adjustment are therefore highly desired. Here we provide a method to predictably design genetic toggle switches with predetermined bistability. To accomplish this task, a biophysical model that links ribosome binding site (RBS) DNA sequence to toggle switch bistability was first developed by integrating a stochastic model with RBS design method. Then, to parametrize the model, a library of genetic toggle switch mutants was experimentally built, followed by establishing the equivalence between RBS DNA sequences and switch bistability. To test this equivalence, RBS nucleotide sequences for different specified bistabilities were in silico designed and experimentally verified. Results show that the deciphered equivalence is highly predictive for the toggle switch design with predetermined bistability. This method can be generalized to quantitative design of other probabilistic genetic devices in synthetic biology.

SU-E-T-480: Radiobiological Dose Comparison of Single Fraction SRS, Multi-Fraction SRT and Multi-Stage SRS of Large Target Volumes Using the Linear-Quadratic Formula

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ding, C; Hrycushko, B; Jiang, S

2014-06-01

Purpose: To compare the radiobiological effect on large tumors and surrounding normal tissues from single fraction SRS, multi-fractionated SRT, and multi-staged SRS treatment. Methods: An anthropomorphic head phantom with a centrally located large volume target (18.2 cm{sup 3}) was scanned using a 16 slice large bore CT simulator. Scans were imported to the Multiplan treatment planning system where a total prescription dose of 20Gy was used for a single, three staged and three fractionated treatment. Cyber Knife treatment plans were inversely optimized for the target volume to achieve at least 95% coverage of the prescription dose. For the multistage plan,more » the target was segmented into three subtargets having similar volume and shape. Staged plans for individual subtargets were generated based on a planning technique where the beam MUs of the original plan on the total target volume are changed by weighting the MUs based on projected beam lengths within each subtarget. Dose matrices for each plan were export in DICOM format and used to calculate equivalent dose distributions in 2Gy fractions using an alpha beta ratio of 10 for the target and 3 for normal tissue. Results: Singe fraction SRS, multi-stage plan and multi-fractionated SRT plans had an average 2Gy dose equivalent to the target of 62.89Gy, 37.91Gy and 33.68Gy, respectively. The normal tissue within 12Gy physical dose region had an average 2Gy dose equivalent of 29.55Gy, 16.08Gy and 13.93Gy, respectively. Conclusion: The single fraction SRS plan had the largest predicted biological effect for the target and the surrounding normal tissue. The multi-stage treatment provided for a more potent biologically effect on target compared to the multi-fraction SRT treatments with less biological normal tissue than single-fraction SRS treatment.« less

A novel fully-humanised 3D skin equivalent to model early melanoma invasion

PubMed Central

Hill, David S; Robinson, Neil D P; Caley, Matthew P; Chen, Mei; O’Toole, Edel A; Armstrong, Jane L; Przyborski, Stefan; Lovat, Penny E

2015-01-01

Metastatic melanoma remains incurable, emphasising the acute need for improved research models to investigate the underlying biological mechanisms mediating tumour invasion and metastasis, and to develop more effective targeted therapies to improve clinical outcome. Available animal models of melanoma do not accurately reflect human disease and current in vitro human skin equivalent models incorporating melanoma cells are not fully representative of the human skin microenvironment. We have developed a robust and reproducible, fully-humanised 3D skin equivalent comprising a stratified, terminally differentiated epidermis and a dermal compartment consisting of fibroblast-generated extracellular matrix. Melanoma cells incorporated into the epidermis were able to invade through the basement membrane and into the dermis, mirroring early tumour invasion in vivo. Comparison of our novel 3D melanoma skin equivalent with melanoma in situ and metastatic melanoma indicates this model accurately recreates features of disease pathology, making it a physiologically representative model of early radial and vertical growth phase melanoma invasion. PMID:26330548

EUD-based biological optimization for carbon ion therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brüningk, Sarah C., E-mail: sarah.brueningk@icr.ac.uk; Kamp, Florian; Wilkens, Jan J.

2015-11-15

Purpose: Treatment planning for carbon ion therapy requires an accurate modeling of the biological response of each tissue to estimate the clinical outcome of a treatment. The relative biological effectiveness (RBE) accounts for this biological response on a cellular level but does not refer to the actual impact on the organ as a whole. For photon therapy, the concept of equivalent uniform dose (EUD) represents a simple model to take the organ response into account, yet so far no formulation of EUD has been reported that is suitable to carbon ion therapy. The authors introduce the concept of an equivalentmore » uniform effect (EUE) that is directly applicable to both ion and photon therapies and exemplarily implemented it as a basis for biological treatment plan optimization for carbon ion therapy. Methods: In addition to a classical EUD concept, which calculates a generalized mean over the RBE-weighted dose distribution, the authors propose the EUE to simplify the optimization process of carbon ion therapy plans. The EUE is defined as the biologically equivalent uniform effect that yields the same probability of injury as the inhomogeneous effect distribution in an organ. Its mathematical formulation is based on the generalized mean effect using an effect-volume parameter to account for different organ architectures and is thus independent of a reference radiation. For both EUD concepts, quadratic and logistic objective functions are implemented into a research treatment planning system. A flexible implementation allows choosing for each structure between biological effect constraints per voxel and EUD constraints per structure. Exemplary treatment plans are calculated for a head-and-neck patient for multiple combinations of objective functions and optimization parameters. Results: Treatment plans optimized using an EUE-based objective function were comparable to those optimized with an RBE-weighted EUD-based approach. In agreement with previous results from photon therapy, the optimization by biological objective functions resulted in slightly superior treatment plans in terms of final EUD for the organs at risk (OARs) compared to voxel-based optimization approaches. This observation was made independent of the underlying objective function metric. An absolute gain in OAR sparing was observed for quadratic objective functions, whereas intersecting DVHs were found for logistic approaches. Even for considerable under- or overestimations of the used effect- or dose–volume parameters during the optimization, treatment plans were obtained that were of similar quality as the results of a voxel-based optimization. Conclusions: EUD-based optimization with either of the presented concepts can successfully be applied to treatment plan optimization. This makes EUE-based optimization for carbon ion therapy a useful tool to optimize more specifically in the sense of biological outcome while voxel-to-voxel variations of the biological effectiveness are still properly accounted for. This may be advantageous in terms of computational cost during treatment plan optimization but also enables a straight forward comparison of different fractionation schemes or treatment modalities.« less

Dioxin equivalency: Challenge to dose extrapolation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brown, J.F. Jr.; Silkworth, J.B.

1995-12-31

Extensive research has shown that all biological effects of dioxin-like agents are mediated via a single biochemical target, the Ah receptor (AhR), and that the relative biologic potencies of such agents in any given system, coupled with their exposure levels, may be described in terms of toxic equivalents (TEQ). It has also shown that the TEQ sources include not only chlorinated species such as the dioxins (PCDDs), PCDFs, and coplanar PCBs, but also non-chlorinated substances such as the PAHs of wood smoke, the AhR agonists of cooked meat, and the indolocarbazol (ICZ) derived from cruciferous vegetables. Humans have probably hadmore » elevated exposures to these non-chlorinated TEQ sources ever since the discoveries of fire, cooking, and the culinary use of Brassica spp. Recent assays of CYP1A2 induction show that these ``natural`` or ``traditional`` AhR agonists are contributing 50--100 times as much to average human TEQ exposures as do the chlorinated xenobiotics. Currently, the safe doses of the xenobiotic TEQ sources are estimated from their NOAELs and large extrapolation factors, derived from arbitrary mathematical models, whereas the NOAELs themselves are regarded as the safe doses for the TEQs of traditional dietary components. Available scientific data can neither support nor refute either approach to assessing the health risk of an individual chemical substance. However, if two substances be toxicologically equivalent, then their TEQ-adjusted health risks must also be equivalent, and the same dose extrapolation procedure should be used for both.« less

Expression of proliferative and inflammatory markers in a full-thickness human skin equivalent following exposure to the model sulfur mustard vesicant, 2-chloroethyl ethyl sulfide

PubMed Central

Black, Adrienne T.; Hayden, Patrick J.; Casillas, Robert P.; Heck, Diane E.; Gerecke, Donald R.; Sinko, Patrick J.; Laskin, Debra L.; Laskin, Jeffrey D.

2010-01-01

Sulfur mustard is a potent vesicant that induces inflammation, edema and blistering following dermal exposure. To assess molecular mechanisms mediating these responses, we analyzed the effects of the model sulfur mustard vesicant, 2-chloroethyl ethyl sulfide, on EpiDerm-FT™, a commercially available full-thickness human skin equivalent. CEES (100–1000 μM) caused a concentration-dependent increase in pyknotic nuclei and vacuolization in basal keratinocytes; at high concentrations (300–1000 μM), CEES also disrupted keratin filament architecture in the stratum corneum. This was associated with time-dependent increases in expression of proliferating cell nuclear antigen, a marker of cell proliferation, and poly(ADP-ribose) polymerase (PARP) and phosphorylated histone H2AX, markers of DNA damage. Concentration- and time-dependent increases in mRNA and protein expression of eicosanoid biosynthetic enzymes including COX-2, 5-lipoxygenase, microsomal PGE2 synthases, leukotriene (LT) A4 hydrolase and LTC4 synthase were observed in CEES-treated skin equivalents, as well as in antioxidant enzymes, glutathione S-transferases A1–2 (GSTA1–2), GSTA3 and GSTA4. These data demonstrate that CEES induces rapid cellular damage, cytotoxicity and inflammation in full-thickness skin equivalents. These effects are similar to human responses to vesicants in vivo and suggest that the full thickness skin equivalent is a useful in vitro model to characterize the biological effects of mustards and to develop potential therapeutics. PMID:20840853

Expression of proliferative and inflammatory markers in a full-thickness human skin equivalent following exposure to the model sulfur mustard vesicant, 2-chloroethyl ethyl sulfide.

PubMed

Black, Adrienne T; Hayden, Patrick J; Casillas, Robert P; Heck, Diane E; Gerecke, Donald R; Sinko, Patrick J; Laskin, Debra L; Laskin, Jeffrey D

2010-12-01

Sulfur mustard is a potent vesicant that induces inflammation, edema and blistering following dermal exposure. To assess molecular mechanisms mediating these responses, we analyzed the effects of the model sulfur mustard vesicant, 2-chloroethyl ethyl sulfide, on EpiDerm-FT™, a commercially available full-thickness human skin equivalent. CEES (100-1000 μM) caused a concentration-dependent increase in pyknotic nuclei and vacuolization in basal keratinocytes; at high concentrations (300-1000 μM), CEES also disrupted keratin filament architecture in the stratum corneum. This was associated with time-dependent increases in expression of proliferating cell nuclear antigen, a marker of cell proliferation, and poly(ADP-ribose) polymerase (PARP) and phosphorylated histone H2AX, markers of DNA damage. Concentration- and time-dependent increases in mRNA and protein expression of eicosanoid biosynthetic enzymes including COX-2, 5-lipoxygenase, microsomal PGE₂ synthases, leukotriene (LT) A₄ hydrolase and LTC₄ synthase were observed in CEES-treated skin equivalents, as well as in antioxidant enzymes, glutathione S-transferases A1-2 (GSTA1-2), GSTA3 and GSTA4. These data demonstrate that CEES induces rapid cellular damage, cytotoxicity and inflammation in full-thickness skin equivalents. These effects are similar to human responses to vesicants in vivo and suggest that the full thickness skin equivalent is a useful in vitro model to characterize the biological effects of mustards and to develop potential therapeutics. Copyright © 2010 Elsevier Inc. All rights reserved.

In vivo CH3(CH2)11SAu SAM electrodes in the beating heart: in situ analytical studies relevant to pacemakers and interstitial biosensors.

PubMed

Chou, Howard A; Zavitz, Daniel H; Ovadia, Marc

2003-01-01

To study in vivo modification of the SAM equivalent circuit when a highly ordered SAM is used as a bioelectrode, dodecanethiolate SAM-Au intramuscular electrodes were studied in living rat heart in a challenging in situ perfused rat model by impedance spectroscopy, cyclic voltammetry, and neutron activation analysis (NAA). The SAM layer experienced disintegration in vivo biological system, as NAA detected the presence of Au atoms that had leached into the surrounding living tissue. Therefore, the underlying Au surface became exposed during biological implant. Study by impedance spectroscopy, however, revealed perfect capacitive behavior for the SAM, similar to in vitro behavior. Electrodes showed a pure capacitive Nyquist plot with 86.1-89.4 degrees near-vertical line segments as the equivalent circuit locus, as for a parallel plate capacitor. Impedance magnitude varied linearly with 1/omega excluding diffusionally limited ionic charge transport. There was no diffusional conductive element Z(W infinity ) or spatially confined Warburg impedance Z(D). The effect of in vivo exposure of a highly ordered SAM is a 'sealing over' effect of new defects by the binding of proteinaceous or lipid species in the biological milieu, a fact of significance for SAM electrodes used either as pacemaker electrodes or as a platform for in vivo biosensors.

A proposed performance index for galactic cosmic ray shielding materials

NASA Technical Reports Server (NTRS)

Wilson, John W.; Wood, J. S.; Shinn, Judy L.; Cucinotta, Francis A.; Nealy, John E.

1993-01-01

In past studies, the reductions in absorbed dose and dose equivalent due to choice of material composition have been used to indicate shield effectiveness against exposure to galactic cosmic rays. However, these quantities are highly inaccurate in assessing shield effectiveness for protection against the biological effects of long-term exposure to the galactic heavy ions. A new quantity for shield performance is defined that correlates well with cell killing and cell transformation behind various shield thicknesses and materials. In addition, a relative performance index is identified that is inversely related to biological injury for different materials at a fixed shield mass and is directly related to the ratio of the fourth- and the second-order linear energy transfer (LET) moments.

Linear energy transfer in water phantom within SHIELD-HIT transport code

NASA Astrophysics Data System (ADS)

Ergun, A.; Sobolevsky, N.; Botvina, A. S.; Buyukcizmeci, N.; Latysheva, L.; Ogul, R.

2017-02-01

The effect of irradiation in tissue is important in hadron therapy for the dose measurement and treatment planning. This biological effect is defined by an equivalent dose H which depends on the Linear Energy Transfer (LET). Usually, H can be expressed in terms of the absorbed dose D and the quality factor K of the radiation under consideration. In literature, various types of transport codes have been used for modeling and simulation of the interaction of the beams of protons and heavier ions with tissue-equivalent materials. In this presentation we used SHIELD-HIT code to simulate decomposition of the absorbed dose by LET in water for 16O beams. A more detailed description of capabilities of the SHIELD-HIT code can be found in the literature.

Measurements of the neutron spectrum in transit to Mars on the Mars Science Laboratory.

PubMed

Köhler, J; Ehresmann, B; Zeitlin, C; Wimmer-Schweingruber, R F; Hassler, D M; Reitz, G; Brinza, D E; Appel, J; Böttcher, S; Böhm, E; Burmeister, S; Guo, J; Lohf, H; Martin, C; Posner, A; Rafkin, S

2015-04-01

The Mars Science Laboratory spacecraft, containing the Curiosity rover, was launched to Mars on 26 November 2011. Although designed for measuring the radiation on the surface of Mars, the Radiation Assessment Detector (RAD) measured the radiation environment inside the spacecraft during most of the 253-day, 560-million-kilometer cruise to Mars. An important factor for determining the biological impact of the radiation environment inside the spacecraft is the specific contribution of neutrons with their high biological effectiveness. We apply an inversion method (based on a maximum-likelihood estimation) to calculate the neutron and gamma spectra from the RAD neutral particle measurements. The measured neutron spectrum (12-436 MeV) translates into a radiation dose rate of 3.8±1.2 μGy/day and a dose equivalent of 19±5 μSv/day. Extrapolating the measured spectrum (0.1-1000 MeV), we find that the total neutron-induced dose rate is 6±2 μGy/day and the dose equivalent rate is 30±10 μSv/day. For a 360 day round-trip from Earth to Mars with comparable shielding, this translates into a neutron induced dose equivalent of about 11±4 mSv. Copyright © 2015 The Committee on Space Research (COSPAR). Published by Elsevier Ltd. All rights reserved.

Biologic Effects of Electric and Magnetic Fields Associated with Proposed Project Seafarer

DTIC Science & Technology

1977-01-01

controlled laboratory conditions. The differences were equivalent to those produced by 0 temperature changes of about 1 C, which would affect only...with the control grouo .! 13 Finally, Krueger and his colleagues have investigated the effects of electromagnetic fields on fecundity in chickens. One...flight from a release point 18 miles (29 km) west of the home colony, control birds (with non -magnetic nylon disks glued to their 0 heads) headed

Exposure to BTEX and Ethers in Petrol Station Attendants and Proposal of Biological Exposure Equivalents for Urinary Benzene and MTBE.

PubMed

Campo, Laura; Rossella, Federica; Mercadante, Rosa; Fustinoni, Silvia

2016-04-01

To assess exposure to benzene (BEN) and other aromatic compounds (toluene, ethylbenzene, m+p-xylene, o-xylene) (BTEX), methyl tert-butyl ether (MTBE), and ethyl tert-butyl ether (ETBE) in petrol station workers using air sampling and biological monitoring and to propose biological equivalents to occupational limit values. Eighty-nine petrol station workers and 90 control subjects were investigated. Personal exposure to airborne BTEX and ethers was assessed during a mid-week shift; urine samples were collected at the beginning of the work week, prior to and at the end of air sampling. Petrol station workers had median airborne exposures to benzene and MTBE of 59 and 408 µg m(-3), respectively, with urinary benzene (BEN-U) and MTBE (MTBE-U) of 339 and 780 ng l(-1), respectively. Concentrations in petrol station workers were higher than in control subjects. There were significant positive correlations between airborne exposure and the corresponding biological marker, with Pearson's correlation coefficient (r) values of 0.437 and 0.865 for benzene and MTBE, respectively. There was also a strong correlation between airborne benzene and urinary MTBE (r = 0.835). Multiple linear regression analysis showed that the urinary levels of benzene were influenced by personal airborne exposure, urinary creatinine, and tobacco smoking [determination coefficient (R(2)) 0.572], while MTBE-U was influenced only by personal exposure (R(2) = 0.741). BEN-U and MTBE-U are sensitive and specific biomarkers of low occupational exposures. We propose using BEN-U as biomarker of exposure to benzene in nonsmokers and suggest 1457 ng l(-1) in end shift urine samples as biological exposure equivalent to the EU occupational limit value of 1 p.p.m.; for both smokers and nonsmokers, MTBE-U may be proposed as a surrogate biomarker of benzene exposure, with a biological exposure equivalent of 22 µg l(-1) in end shift samples. For MTBE exposure, we suggest the use of MTBE-U with a biological exposure equivalent of 22 µg l(-1) corresponding to the occupational limit value of 50 p.p.m. © The Author 2015. Published by Oxford University Press on behalf of the British Occupational Hygiene Society.

[The temperature factor and magnetic noise under the conditions of stochastic resonance of magnetosomes].

PubMed

Bingi, V N; Chernavskiĭ, D S; Rubin, A B

2006-01-01

The influence of magnetic noise on the dynamics of magnetic nanoparticles under the conditions of stochastic resonance is considered. The effect of the magnetic noise is shown to be equivalent to the growth of the effective thermostat temperature for the particles at the permanent actual temperature of the medium. This regularity may be used for testing the hypothesis on the involvement of magnetic nanoparticles in the formation of biological effects of weak magnetic fields.

Demystifying the U.S. Food and Drug Administration: I. Understanding agency structure and function.

PubMed

Levi, Benjamin; Lisiecki, Jeffrey; Rubin, Peter; D'Amico, Richard A; Hume, Keith M; Seward, Bill; Cederna, Paul S

2014-06-01

The U.S. Food and Drug Administration is the government agency responsible for oversight of the safety and efficacy of pharmaceuticals and devices, including biologics and devices that combine biologics with other materials. Within the U.S. Food and Drug Administration, the Center for Biologics Evaluation and Research is specifically responsible for the evaluation and approval of biological products. This department of the U.S. Food and Drug Administration has a series of mechanisms in place to aid researchers in the process of developing new biologics. This article outlines the study phases involved in developing new biologics and how the Center for Biologics Evaluation and Research and investigators can work together to facilitate this process. It also discusses issues specific to biologics that have been encountered in the past and that investigators should consider when developing and obtaining approval for new biologics. The equivalent center within the U.S. Food and Drug Administration for approving medical devices is the Center for Devices and Radiological Health. The equivalent process of development and approval of medical devices is similarly discussed. Finally, essential contacts for investigators within the Center for Biologics Evaluation and Research and the Center for Devices and Radiological Health are provided.

Sample size determination for a three-arm equivalence trial of Poisson and negative binomial responses.

PubMed

Chang, Yu-Wei; Tsong, Yi; Zhao, Zhigen

2017-01-01

Assessing equivalence or similarity has drawn much attention recently as many drug products have lost or will lose their patents in the next few years, especially certain best-selling biologics. To claim equivalence between the test treatment and the reference treatment when assay sensitivity is well established from historical data, one has to demonstrate both superiority of the test treatment over placebo and equivalence between the test treatment and the reference treatment. Thus, there is urgency for practitioners to derive a practical way to calculate sample size for a three-arm equivalence trial. The primary endpoints of a clinical trial may not always be continuous, but may be discrete. In this paper, the authors derive power function and discuss sample size requirement for a three-arm equivalence trial with Poisson and negative binomial clinical endpoints. In addition, the authors examine the effect of the dispersion parameter on the power and the sample size by varying its coefficient from small to large. In extensive numerical studies, the authors demonstrate that required sample size heavily depends on the dispersion parameter. Therefore, misusing a Poisson model for negative binomial data may easily lose power up to 20%, depending on the value of the dispersion parameter.

Experimental derivation of relative biological effectiveness of A-bomb neutrons in Hiroshima and Nagasaki and implications for risk assessment.

PubMed

Sasaki, M S; Nomura, T; Ejima, Y; Utsumi, H; Endo, S; Saito, I; Itoh, T; Hoshi, M

2008-07-01

Epidemiological data on the health effects of A-bomb radiation in Hiroshima and Nagasaki provide the framework for setting limits for radiation risk and radiological protection. However, uncertainty remains in the equivalent dose, because it is generally believed that direct derivation of the relative biological effectiveness (RBE) of neutrons from the epidemiological data on the survivors is difficult. To solve this problem, an alternative approach has been taken. The RBE of polyenergetic neutrons was determined for chromosome aberration formation in human lymphocytes irradiated in vitro, compared with published data for tumor induction in experimental animals, and validated using epidemiological data from A-bomb survivors. The RBE of fission neutrons was dependent on dose but was independent of the energy spectrum. The same RBE regimen was observed for lymphocyte chromosome aberrations and tumors in mice and rats. Used as a weighting factor for A-bomb survivors, this RBE system was superior in eliminating the city difference in chromosome aberration frequencies and cancer mortality. The revision of the equivalent dose of A-bomb radiation using DS02 weighted by this RBE system reduces the cancer risk by a factor of 0.7 compared with the current estimates using DS86, with neutrons weighted by a constant RBE of 10.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Black, Adrienne T.; Hayden, Patrick J.; Casillas, Robert P.

Sulfur mustard is a potent vesicant that induces inflammation, edema and blistering following dermal exposure. To assess molecular mechanisms mediating these responses, we analyzed the effects of the model sulfur mustard vesicant, 2-chloroethyl ethyl sulfide, on EpiDerm-FT{sup TM}, a commercially available full-thickness human skin equivalent. CEES (100-1000 {mu}M) caused a concentration-dependent increase in pyknotic nuclei and vacuolization in basal keratinocytes; at high concentrations (300-1000 {mu}M), CEES also disrupted keratin filament architecture in the stratum corneum. This was associated with time-dependent increases in expression of proliferating cell nuclear antigen, a marker of cell proliferation, and poly(ADP-ribose) polymerase (PARP) and phosphorylated histonemore » H2AX, markers of DNA damage. Concentration- and time-dependent increases in mRNA and protein expression of eicosanoid biosynthetic enzymes including COX-2, 5-lipoxygenase, microsomal PGE{sub 2} synthases, leukotriene (LT) A{sub 4} hydrolase and LTC{sub 4} synthase were observed in CEES-treated skin equivalents, as well as in antioxidant enzymes, glutathione S-transferases A1-2 (GSTA1-2), GSTA3 and GSTA4. These data demonstrate that CEES induces rapid cellular damage, cytotoxicity and inflammation in full-thickness skin equivalents. These effects are similar to human responses to vesicants in vivo and suggest that the full thickness skin equivalent is a useful in vitro model to characterize the biological effects of mustards and to develop potential therapeutics.« less

Radiobiological equivalent of low/high dose rate brachytherapy and evaluation of tumor and normal responses to the dose.

PubMed

Manimaran, S

2007-06-01

The aim of this study was to compare the biological equivalent of low-dose-rate (LDR) and high-dose-rate (HDR) brachytherapy in terms of the more recent linear quadratic (LQ) model, which leads to theoretical estimation of biological equivalence. One of the key features of the LQ model is that it allows a more systematic radiobiological comparison between different types of treatment because the main parameters alpha/beta and micro are tissue-specific. Such comparisons also allow assessment of the likely change in the therapeutic ratio when switching between LDR and HDR treatments. The main application of LQ methodology, which focuses on by increasing the availability of remote afterloading units, has been to design fractionated HDR treatments that can replace existing LDR techniques. In this study, with LDR treatments (39 Gy in 48 h) equivalent to 11 fractions of HDR irradiation at the experimental level, there are increasing reports of reproducible animal models that may be used to investigate the biological basis of brachytherapy and to help confirm theoretical predictions. This is a timely development owing to the nonavailability of sufficient retrospective patient data analysis. It appears that HDR brachytherapy is likely to be a viable alternative to LDR only if it is delivered without a prohibitively large number of fractions (e.g., fewer than 11). With increased scientific understanding and technological capability, the prospect of a dose equivalent to HDR brachytherapy will allow greater utilization of the concepts discussed in this article.

Signal transduction in Mimosa pudica: biologically closed electrical circuits.

PubMed

Volkov, Alexander G; Foster, Justin C; Markin, Vladislav S

2010-05-01

Biologically closed electrical circuits operate over large distances in biological tissues. The activation of such circuits can lead to various physiological and biophysical responses. Here, we analyse the biologically closed electrical circuits of the sensitive plant Mimosa pudica Linn. using electrostimulation of a petiole or pulvinus by the charged capacitor method, and evaluate the equivalent electrical scheme of electrical signal transduction inside the plant. The discharge of a 100 microF capacitor in the pulvinus resulted in the downward fall of the petiole in a few seconds, if the capacitor was charged beforehand by a 1.5 V power supply. Upon disconnection of the capacitor from Ag/AgCl electrodes, the petiole slowly relaxed to the initial position. The electrical properties of the M. pudica were investigated, and an equivalent electrical circuit was proposed that explains the experimental data.

Interaction of silver nanoparticles with biological objects: antimicrobial properties and toxicity for the other living organisms

NASA Astrophysics Data System (ADS)

Egorova, E. M.

2011-04-01

This paper presents several examples of the biological effects of small-sized silver nanoparticles (10.5±3.5nm) observed in experiments on bacteria, slim mold, unicellular alga and plant seeds. The nanoparticles were prepared by the biochemical synthesis, based on the reduction of metal ions in reverse vicelles by biological reductants - natural plant pigments (flavonoids). It is found that, except for the plant seeds, silver nanoparticles (SNP) act as a strong toxic agent, both in water solution and as part of liquid-phase material. It is shown also that the biological action of silver nanoparticles can not be reduced to the toxic action of silver ions in equivalent concentrations or to that of the surfactant (the SNP stabilizer) present in the SNP water solution. Possible SNP applications are suggested.

Equivalency of general biology (for majors) across a state-system

NASA Astrophysics Data System (ADS)

Regier, Kimberly Fayette

General biology courses (for majors) are often transferred from one institution to another. These courses must prepare students for upper division courses in biology. A survey of U.S. college biology faculty was conducted and revealed that more 4-year faculty do not believe that all general biology courses are equivalent. An evaluation of course grades in two upper division biology courses at University of Colorado Denver (N = 2129) based upon course grades in general biology and the type of institution where general biology was taken (2-year school, 4-year, in-residence at UCD, AP credit, CLEP credit, or IB credit) was conducted. Students who transferred general biology credit received lower grades in upper division biology courses and withdrew from upper division biology courses more frequently. Syllabi from a small sample (N = 9) of general biology courses offered at Colorado 2- and 4-year schools show variation in course design. Only 30% of the courses had detailed learning objectives. Sample exams reveal a range in variation between 3-69% of questions requiring higher-order thinking according to Bloom's Taxonomy. Increasing communication between high school, 2-year and 4-year biology faculty is necessary if consistency is to be gained. Professional development for faculty to increase awareness about exam development, curriculum alignment, and curriculum mapping may reduce the disparities between the preparation of students in biology. Transfer student grade outcomes should be further investigated across the state.

Dual Causality and the Autonomy of Biology.

PubMed

Bock, Walter J

2017-03-01

Ernst Mayr's concept of dual causality in biology with the two forms of causes (proximate and ultimate) continues to provide an essential foundation for the philosophy of biology. They are equivalent to functional (=proximate) and evolutionary (=ultimate) causes with both required for full biological explanations. The natural sciences can be classified into nomological, historical nomological and historical dual causality, the last including only biology. Because evolutionary causality is unique to biology and must be included for all complete biological explanations, biology is autonomous from the physical sciences.

Water and tissue equivalence properties of biological materials for photons, electrons, protons and alpha particles in the energy region 10 keV-1 GeV: a comparative study.

PubMed

Kurudirek, Murat

2016-09-01

To compare some biological materials in respect to the water and tissue equivalence properties for photon, electron, proton and alpha particle interactions as means of the effective atomic number (Zeff) and electron density (Ne). A Z-wise interpolation procedure has been adopted for calculation of Zeff using the mass attenuation coefficients for photons and the mass stopping powers for charged particles. At relatively low energies (100 keV-3 MeV), Zeff and Ne for photons and electrons were found to be constant while they vary much more for protons and alpha particles. In contrast, Zeff and Ne for protons and alpha particles were found to be constant after 3 MeV whereas for photons and electrons they were found to increase with the increasing energy. Also, muscle eq. liquid (with sucrose) have Zeff and Ne values close to the Muscle Skeletal (ICRP) and Muscle Striated (ICRU) within low relative differences below 9%. Muscle eq. liquid (without sucrose) have Zeff and Ne values close to the Muscle Skeletal (ICRP) and Muscle Striated (ICRU) with difference below 10%. The reported data should be useful in determining best water as well as tissue equivalent materials for photon, electron, proton and alpha particle interactions.

Measurements of the Martian Gamma/Neutron Spectra with MSL/RAD

NASA Astrophysics Data System (ADS)

Kohler, J.; Zeitlin, C. J.; Ehresmann, B.; Wimmer-Schweingruber, R. F.; Hassler, D.; Reitz, G.; Brinza, D.; Weigle, E.; Boettcher, S.; Burmeister, S.; Guo, J.; Martin-Garcia, C.; Boehm, E.; Posner, A.; Rafkin, S. C.; Kortmann, O.

2013-12-01

The Radiation Assessment Detector (RAD) onboard Mars Science Laboratory's rover curiosity measures the energetic charged and neutral particle spectra and the radiation dose rate on the Martian surface. An important factor for determining the biological impact of the Martian surface radiation is the specific contribution of neutrons, which possess a high biological effectiveness. In contrast to charged particles, neutrons and gamma rays are generally only measured indirectly. Their measurement is the result of a complex convolution of the incident particle spectrum with the measurement process. We apply an inversion method to calculate the gamma/neutron spectra from the RAD neutral particle measurements. Here we show first measurements of the Martian gamma/neutron spectra and compare them to theoretical predictions. We find that the shape of the gamma spectrum is very similar to the predicted one, but with a ~50% higher intensity. The measured neutron spectrum agrees well with prediction up to ~100 MeV, but shows a considerably increased intensity for higher energies. The measured neutron spectrum translates into a radiation dose rate of 25 μGy/day and a dose equivalent rate of 106 μSv/day. This corresponds to 10% of the total surface dose rate, and 15% of the biological relevant surface dose equivalent rate on Mars. Measuring the Martian neutron spectra is an essential step for determining the mutagenic influences to past or present life at or beneath the Martian surface as well as the radiation hazard for future human exploration, including the shielding design of a potential habitat. The contribution of neutrons to the dose equivalent increases considerably with shielding thickness, so our measurements provide an important figure to mitigate cancer risk.

Risk equivalent of exposure versus dose of radiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bond, V.P.

This report describes a risk analysis study of low-dose irradiation and the resulting biological effects on a cell. The author describes fundamental differences between the effects of high-level exposure (HLE) and low-level exposure (LLE). He stresses that the concept of absorbed dose to an organ is not a dose but a level of effect produced by a particular number of particles. He discusses the confusion between a linear-proportional representation of dose limits and a threshold-curvilinear representation, suggesting that a LLE is a composite of both systems. (TEM)

Developing Unconstrained Methods for Enzyme Evolution

DTIC Science & Technology

2014-09-19

Equivalent: Total Number: Sunil Kumar 1.00 1.00 1 PERCENT_SUPPORTEDNAME FTE Equivalent: Total Number: National Academy Member John C. Chaput 0.10 No 0.10...synthetic ATP-binding protein leads to novel phenotypic changes in Escherichia coli. ACS Chemical Biology 8, 451-456. c. Student Support Dr. Sunil

Understanding Phylogenies in Biology: The Influence of a Gestalt Perceptual Principle

ERIC Educational Resources Information Center

Novick, Laura R.; Catley, Kefyn M.

2007-01-01

Cladograms, hierarchical diagrams depicting evolutionary histories among (groups of) species, are commonly drawn in 2 informationally equivalent formats--tree and ladder. The authors hypothesize that these formats are not computationally equivalent because the Gestalt principle of good continuation obscures the hierarchical structure of ladders.…

Quantification of biological tissue and construction of patient equivalent phantom (skull and chest) for infants (1-5 years old)

NASA Astrophysics Data System (ADS)

Alves, A. F.; Pina, D. R.; Bacchim Neto, F. A.; Ribeiro, S. M.; Miranda, J. R. A.

2014-03-01

Our main purpose in this study was to quantify biological tissue in computed tomography (CT) examinations with the aim of developing a skull and a chest patient equivalent phantom (PEP), both specific to infants, aged between 1 and 5 years old. This type of phantom is widely used in the development of optimization procedures for radiographic techniques, especially in computed radiography (CR) systems. In order to classify and quantify the biological tissue, we used a computational algorithm developed in Matlab ®. The algorithm performed a histogram of each CT slice followed by a Gaussian fitting of each tissue type. The algorithm determined the mean thickness for the biological tissues (bone, soft, fat, and lung) and also converted them into the corresponding thicknesses of the simulator material (aluminum, PMMA, and air). We retrospectively analyzed 148 CT examinations of infant patients, 56 for skull exams and 92 were for chest. The results provided sufficient data to construct a phantom to simulate the infant chest and skull in the posterior-anterior or anterior-posterior (PA/AP) view. Both patient equivalent phantoms developed in this study can be used to assess physical variables such as noise power spectrum (NPS) and signal to noise ratio (SNR) or perform dosimetric control specific to pediatric protocols.

[Modeling and experimental study on frequency-domain electricity properties of biological materials].

PubMed

Tian, Hua; Luo, Shiqiang; Zhang, Rui; Yang, Gang; Huang, Hua

2009-12-01

Frequency-domain electricity properties of four objects, including bullfrog skin, bullfrog muscle, triply distilled water and 0.9% NaCl, were tested in the range of 100Hz-10MHz using home-made electrode and measuring system. The experimental results showed that the resistance of 0.9% NaCl decreased dramatically, that the amplitude frequency characteristics of bullfrog's muscle and skin were similar, but that of triply distilled water did not change significantly. The frequency dependence of 0.9% NaCl showed that the electrode had great influence on the measuring system, so a new equivalent circuit model based on the electrode system was needed. These findings suggest that the new five-parameter equivalent circuit model, which embodies considerations on the interaction between electrodes and tissues, is a reasonable equivalent circuit for studying the electrical characteristics of biological materials.

Biomagnification of bioassay derived 2,3,7,8-tetrachlorodibenzo-p-dioxin equivalents

USGS Publications Warehouse

Jones, P.D.; Ankley, G.T.; Best, D. A.; Crawford, R.; DeGalan, N.; Giesy, J.P.; Kubiak, T.J.; Ludwig, J. P.; Newsted, J.L.; Tillitt, D. E.; Verbrugge, D.A.

1993-01-01

In recent years contamination of the Great Lakes ecosystem with planar chlorinated hydrocarbons (PCHs) has attracted considerable concern due to their known reproductive and teratogenic effects. The H4IIE bioassay has been standardized as a means of measuring the biological potency of a PCH mixture as 2,3,7,8-tetrachloro-p-dibenzodioxin equivalents (TCDD-EQ). Using this bioassay we have investigated the biomagnification of TCDD-EQ in a semi-closed ecosystem. The biomagnification of TCDD-EQ is demonstrated and results indicate that the food chain is the major pathway for TCDD-EQ through this ecosystem. The H4IIE assay system is demonstrated to be a viable integrative measure of the total concentration of TCDD-EQ in different trophic levels.

Temporal Lobe Reactions After Radiotherapy With Carbon Ions: Incidence and Estimation of the Relative Biological Effectiveness by the Local Effect Model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schlampp, Ingmar; Karger, Christian P.; Jaekel, Oliver

2011-07-01

Purpose: To identify predictors for the development of temporal lobe reactions (TLR) after carbon ion radiation therapy (RT) for radiation-resistant tumors in the central nervous system and to evaluate the predictions of the local effect model (LEM) used for calculation of the biologically effective dose. Methods and Materials: This retrospective study reports the TLR rates in patients with skull base chordomas and chondrosarcomas irradiated with carbon ions at GSI, Darmstadt, Germany, in the years 2002 and 2003. Calculation of the relative biological effectiveness and dose optimization of treatment plans were performed on the basis of the LEM. Clinical examinations andmore » magnetic resonance imaging (MRI) were performed at 3, 6, and 12 months after RT and annually thereafter. Local contrast medium enhancement in temporal lobes, as detected on MRI, was regarded as radiation-induced TLR. Dose-volume histograms of 118 temporal lobes in 59 patients were analyzed, and 16 therapy-associated and 2 patient-associated factors were statistically evaluated for their predictive value for the occurrence of TLR. Results: Median follow-up was 2.5 years (range, 0.3--6.6 years). Age and maximum dose applied to at least 1 cm{sup 3} of the temporal lobe (D{sub max,V-1cm}3, maximum dose in the remaining temporal lobe volume, excluding the volume 1 cm{sup 3} with the highest dose) were found to be the most important predictors for TLR. Dose response curves of D{sub max,V-1cm}3 were calculated. The biologically equivalent tolerance doses for the 5% and 50% probabilities to develop TLR were 68.8 {+-} 3.3 Gy equivalents (GyE) and 87.3 {+-} 2.8 GyE, respectively. Conclusions: D{sub max,V-1cm}3 is predictive for radiation-induced TLR. The tolerance doses obtained seem to be consistent with published data for highly conformal photon and proton irradiations. We could not detect any clinically relevant deviations between clinical findings and expectations based on predictions of the LEM.« less

USSR Report, Space Biology and Aerospace Medicine, Vol. 18, No. 5, September-October 1984

DTIC Science & Technology

1984-11-20

Exchange and Pulmonary Circulation in Man 34 Regional Circulation During Testing on Isokinetic Dynamometer Following 14-Day Bedrest 39 Primate...Indicator of Animal Adaptation to Altitude Hypoxia . 71 Distinctions of Rat Lymphatic Organ Reactions to Acute Stress Factor During Hypokinesia...14, 40, 51].^ Experimental validation of the energy principle of noise effects made it possible to turn to estimation of its equivalent level. The

Integrating biological and social values when prioritizing places for biodiversity conservation.

PubMed

Whitehead, Amy L; Kujala, Heini; Ives, Christopher D; Gordon, Ascelin; Lentini, Pia E; Wintle, Brendan A; Nicholson, Emily; Raymond, Christopher M

2014-08-01

The consideration of information on social values in conjunction with biological data is critical for achieving both socially acceptable and scientifically defensible conservation planning outcomes. However, the influence of social values on spatial conservation priorities has received limited attention and is poorly understood. We present an approach that incorporates quantitative data on social values for conservation and social preferences for development into spatial conservation planning. We undertook a public participation GIS survey to spatially represent social values and development preferences and used species distribution models for 7 threatened fauna species to represent biological values. These spatially explicit data were simultaneously included in the conservation planning software Zonation to examine how conservation priorities changed with the inclusion of social data. Integrating spatially explicit information about social values and development preferences with biological data produced prioritizations that differed spatially from the solution based on only biological data. However, the integrated solutions protected a similar proportion of the species' distributions, indicating that Zonation effectively combined the biological and social data to produce socially feasible conservation solutions of approximately equivalent biological value. We were able to identify areas of the landscape where synergies and conflicts between different value sets are likely to occur. Identification of these synergies and conflicts will allow decision makers to target communication strategies to specific areas and ensure effective community engagement and positive conservation outcomes. © 2014 Society for Conservation Biology.

Biological toxicity of lanthanide elements on algae.

PubMed

Tai, Peidong; Zhao, Qing; Su, Dan; Li, Peijun; Stagnitti, Frank

2010-08-01

The biological toxicity of lanthanides on marine monocellular algae was investigated. The specific objective of this research was to establish the relationship between the abundance in the seawater of lanthanides and their biological toxicities on marine monocellular algae. The results showed that all single lanthanides had similar toxic effects on Skeletonema costatum. High concentrations of lanthanides (29.04+/-0.61 micromol L(-1)) resulted in 50% reduction in growth of algae compared to the controls (0 micromol L(-1)) after 96 h (96 h-EC50). The biological toxicity of 13 lanthanides on marine monocellular algae was unrelated with the abundance of different lanthanide elements in nature, and the "Harkins rule" was not appropriate for the lanthanides. A mixed solution that contained equivalent concentrations of each lanthanide element had the same inhibition effect on algae cells as each individual lanthanide element at the same total concentration. This phenomenon is unique compared to the groups of other elements in the periodic table. Hence, we speculate that the monocellular organisms might not be able to sufficiently differentiate between the almost chemically identical lanthanide elements. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

Modified methods for growing 3-D skin equivalents: an update.

PubMed

Lamb, Rebecca; Ambler, Carrie A

2014-01-01

Artificial epidermis can be reconstituted in vitro by seeding primary epidermal cells (keratinocytes) onto a supportive substrate and then growing the developing skin equivalent at the air-liquid interface. In vitro skin models are widely used to study skin biology and for industrial drug and cosmetic testing. Here, we describe updated methods for growing 3-dimensional skin equivalents using de-vitalized, de-epidermalized dermis (DED) substrates including methods for DED substrate preparation, cell seeding, growth conditions, and fixation procedures.

Fluctuation relations between hierarchical kinetically equivalent networks with Arrhenius-type transitions and their roles in systems and structural biology.

PubMed

Deng, De-Ming; Lu, Yi-Ta; Chang, Cheng-Hung

2017-06-01

The legality of using simple kinetic schemes to determine the stochastic properties of a complex system depends on whether the fluctuations generated from hierarchical equivalent schemes are consistent with one another. To analyze this consistency, we perform lumping processes on the stochastic differential equations and the generalized fluctuation-dissipation theorem and apply them to networks with the frequently encountered Arrhenius-type transition rates. The explicit Langevin force derived from those networks enables us to calculate the state fluctuations caused by the intrinsic and extrinsic noises on the free energy surface and deduce their relations between kinetically equivalent networks. In addition to its applicability to wide classes of network related systems, such as those in structural and systems biology, the result sheds light on the fluctuation relations for general physical variables in Keizer's canonical theory.

Approximating the Probability of Mortality Due to Protracted Radiation Exposures

DTIC Science & Technology

2016-06-01

Probability of Fatality 22 Section 9. References Anno , G. H., G. E. McClellan, M. A. Dore, and S. J . Baum, "Biological Effects of Protracted...Defense Threat Reduction Agency 8725 John J . Kingman Road, MS-6201 Fort Belvoir, VA 22060-6201...joule ( J ) erg 1 × 10–7 joule ( J ) kiloton (kt) (TNT equivalent) 4.184 × 1012 joule ( J ) British thermal unit (Btu) (thermochemical) 1.054 350 × 10

United States Air Force Graduate Student Research Program for 1990. Program Technical Report. Volume 3

DTIC Science & Technology

1991-06-05

information would provide more precise control of the vehicle. To this extent, research has been ongoing at the Biological Acoustics Section of AAMRL... researching questions of neurobiology, particularly neurochemistry and neuroanatomy. Furthermore, I am strongly interested in the effects of ionizing and non ...administered to the animal intraperitoneally. Control animals received an injection of saline in an equivalent volume. When the colonic temperature returned to

Shot sequencing based on biological equivalent dose considerations for multiple isocenter Gamma Knife radiosurgery.

PubMed

Ma, Lijun; Lee, Letitia; Barani, Igor; Hwang, Andrew; Fogh, Shannon; Nakamura, Jean; McDermott, Michael; Sneed, Penny; Larson, David A; Sahgal, Arjun

2011-11-21

Rapid delivery of multiple shots or isocenters is one of the hallmarks of Gamma Knife radiosurgery. In this study, we investigated whether the temporal order of shots delivered with Gamma Knife Perfexion would significantly influence the biological equivalent dose for complex multi-isocenter treatments. Twenty single-target cases were selected for analysis. For each case, 3D dose matrices of individual shots were extracted and single-fraction equivalent uniform dose (sEUD) values were determined for all possible shot delivery sequences, corresponding to different patterns of temporal dose delivery within the target. We found significant variations in the sEUD values among these sequences exceeding 15% for certain cases. However, the sequences for the actual treatment delivery were found to agree (<3%) and to correlate (R² = 0.98) excellently with the sequences yielding the maximum sEUD values for all studied cases. This result is applicable for both fast and slow growing tumors with α/β values of 2 to 20 according to the linear-quadratic model. In conclusion, despite large potential variations in different shot sequences for multi-isocenter Gamma Knife treatments, current clinical delivery sequences exhibited consistent biological target dosing that approached that maximally achievable for all studied cases.

Modeling the biophysical effects in a carbon beam delivery line by using Monte Carlo simulations

NASA Astrophysics Data System (ADS)

Cho, Ilsung; Yoo, SeungHoon; Cho, Sungho; Kim, Eun Ho; Song, Yongkeun; Shin, Jae-ik; Jung, Won-Gyun

2016-09-01

The Relative biological effectiveness (RBE) plays an important role in designing a uniform dose response for ion-beam therapy. In this study, the biological effectiveness of a carbon-ion beam delivery system was investigated using Monte Carlo simulations. A carbon-ion beam delivery line was designed for the Korea Heavy Ion Medical Accelerator (KHIMA) project. The GEANT4 simulation tool kit was used to simulate carbon-ion beam transport into media. An incident energy carbon-ion beam with energy in the range between 220 MeV/u and 290 MeV/u was chosen to generate secondary particles. The microdosimetric-kinetic (MK) model was applied to describe the RBE of 10% survival in human salivary-gland (HSG) cells. The RBE weighted dose was estimated as a function of the penetration depth in the water phantom along the incident beam's direction. A biologically photon-equivalent Spread Out Bragg Peak (SOBP) was designed using the RBE-weighted absorbed dose. Finally, the RBE of mixed beams was predicted as a function of the depth in the water phantom.

Use of Concept of Chemotherapy-Equivalent Biologically Effective Dose to Provide Quantitative Evaluation of Contribution of Chemotherapy to Local Tumor Control in Chemoradiotherapy Cervical Cancer Trials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Plataniotis, George A.; Dale, Roger G.

2008-12-01

Purpose: To express the magnitude of the contribution of chemotherapy to local tumor control in chemoradiotherapy cervical cancer trials in terms of the concept of the biologically effective dose. Methods and Materials: The local control rates of both arms of each study (radiotherapy vs. radiotherapy plus chemotherapy) reported from randomized controlled trials of concurrent chemoradiotherapy for cervical cancer were reviewed and expressed using the Poisson model for tumor control probability (TCP) as TCP = exp(-exp E), where E is the logarithm of cell kill. By combining the two TCP values from each study, we calculated the chemotherapy-related log cell killmore » as Ec = ln[(lnTCP{sub Radiotherapy})/(lnTCP{sub Chemoradiotherapy})]. Assuming a range of radiosensitivities ({alpha} = 0.1-0.5 Gy{sup -1}) and taking the calculated log cell kill, we calculated the chemotherapy-BED, and using the linear quadratic model, the number of 2-Gy fractions corresponding to each BED. The effect of a range of tumor volumes and radiosensitivities ({alpha} Gy{sup -1}) on the TCP was also explored. Results: The chemotherapy-equivalent number of 2-Gy fractions range was 0.2-4 and was greater in tumors with lower radiosensitivity. In those tumors with intermediate radiosensitivity ({alpha} = 0.3 Gy{sup -1}), the equivalent number of 2-Gy fractions was 0.6-1.3, corresponding to 120-260 cGy of extra dose. The opportunities for clinically detectable improvement are only available in tumors with intermediate radiosensitivity with {alpha} = 0.22-0.28 Gy{sup -1}. The dependence of TCP on the tumor volume decreases as the radiosensitivity increases. Conclusion: The results of our study have shown that the contribution of chemotherapy to the TCP in cervical cancer is expected to be clinically detectable in larger and less-radiosensitive tumors.« less

Odorant-binding protein-based identification of natural spatial repellents for the African malaria mosquito Anopheles gambiae.

PubMed

Kröber, Thomas; Koussis, Konstantinos; Bourquin, Martine; Tsitoura, Panagiota; Konstantopoulou, Maria; Awolola, Taiwo Sam; Dani, Francesca R; Qiao, Huili; Pelosi, Paolo; Iatrou, Kostas; Guerin, Patrick M

2018-05-01

There is increasing interest in the development of effective mosquito repellents of natural origin to reduce transmission of diseases such as malaria and yellow fever. To achieve this we have employed an in vitro competition assay involving odorant-binding proteins (OBPs) of the malaria mosquito, Anopheles gambiae, with a predominantly female expression bias to identify plant essential oils (EOs) containing bioactive compounds that target mosquito olfactory function. EOs and their fractions capable of binding to such OBPs displayed repellence against female mosquitoes in a laboratory repellent assay. Repellent EOs were subjected to gas chromatographic analysis linked to antennogram (EAG) recordings from female A. gambiae to identify the biologically active constituents. Among these compounds cumin alcohol, carvacrol, ethyl cinnamate and butyl cinnamate proved as effective as DEET at an equivalent dose in the repellent assay, and combinations of carvacrol with either butyl cinnamate or cumin alcohol proved to be significantly more effective than DEET in the assay. When tested as spatial repellents in experimental shelters housing sleeping humans in northern Nigeria a binary mixture of carvacrol plus cumin alcohol caused mosquitoes to leave shelters in significantly higher numbers to those induced by DEET in female Anopheles spp. and in numbers equivalent to that of DEET in Culex spp. mosquitoes. These findings indicate an approach for the identification of biologically active molecules of natural origin serving as repellents for mosquitoes. Copyright © 2018 Elsevier Ltd. All rights reserved.

Molecular mechanism of biological and therapeutical effect of low-intensity laser irradiation

NASA Astrophysics Data System (ADS)

Mostovnikov, Vasili A.; Mostovnikova, Galina R.; Plavski, Vitali Y.; Plavskaja, Ljudmila G.; Morozova, Raisa P.

1995-05-01

The investigations carried out in our group on biological systems of various organization level (enzyme molecules in solution, human and animal cell cultures), allowed us to conclude, that the light-induced changes of spatial structure of cells components form the basis of biological activity (and as a consequence therapeutic effect) of various wavelength low-intensity laser emission. Photophysical mechanism of these changes lies in the reorientation of highregulated anisotropic parts (domains) with the liquid-crystalline type of ordering of the cell components due to the interaction between the electric field and the light induced integral electric dipole of the domain. The mechanism of such reorientation is well established in physics of liquid crystals of nematic type and is known as light induced analogue of Frederix's effect. The following results enable us to draw the conclusion about the determining role of the orientations effects on the biological activity mechanism of low-intensity laser radiation: (i) the possibility of reversible modification of spatial structure and enzyme molecules functional activity under the influence of laser radiation outside the band of their own or admixture absorption; (ii) the dependence of biological effect of laser radiation on the functional activity of cells vs. polarization degree of the light with the maximum photobiological effects observed for linear-polarized radiation; (iii) the equivalence of a static magnetic field and low-intensity laser radiation in action on functional activity of the cells and the lowering of the laser field intensity for the achieving the difinite changes of the cell functional activity in the presence of static magnetic field.

Skin integrated with perfusable vascular channels on a chip.

PubMed

Mori, Nobuhito; Morimoto, Yuya; Takeuchi, Shoji

2017-02-01

This paper describes a method for fabricating perfusable vascular channels coated with endothelial cells within a cultured skin-equivalent by fixing it to a culture device connected to an external pump and tubes. A histological analysis showed that vascular channels were constructed in the skin-equivalent, which showed a conventional dermal/epidermal morphology, and the endothelial cells formed tight junctions on the vascular channel wall. The barrier function of the skin-equivalent was also confirmed. Cell distribution analysis indicated that the vascular channels supplied nutrition to the skin-equivalent. Moreover, the feasibility of a skin-equivalent containing vascular channels as a model for studying vascular absorption was demonstrated by measuring test molecule permeation from the epidermal layer into the vascular channels. The results suggested that this skin-equivalent can be used for skin-on-a-chip applications including drug development, cosmetics testing, and studying skin biology. Copyright © 2016 Elsevier Ltd. All rights reserved.

Increased Course Structure Improves Performance in Introductory Biology

PubMed Central

Freeman, Scott; Haak, David; Wenderoth, Mary Pat

2011-01-01

We tested the hypothesis that highly structured course designs, which implement reading quizzes and/or extensive in-class active-learning activities and weekly practice exams, can lower failure rates in an introductory biology course for majors, compared with low-structure course designs that are based on lecturing and a few high-risk assessments. We controlled for 1) instructor effects by analyzing data from quarters when the same instructor taught the course, 2) exam equivalence with new assessments called the Weighted Bloom's Index and Predicted Exam Score, and 3) student equivalence using a regression-based Predicted Grade. We also tested the hypothesis that points from reading quizzes, clicker questions, and other “practice” assessments in highly structured courses inflate grades and confound comparisons with low-structure course designs. We found no evidence that points from active-learning exercises inflate grades or reduce the impact of exams on final grades. When we controlled for variation in student ability, failure rates were lower in a moderately structured course design and were dramatically lower in a highly structured course design. This result supports the hypothesis that active-learning exercises can make students more skilled learners and help bridge the gap between poorly prepared students and their better-prepared peers. PMID:21633066

Increased course structure improves performance in introductory biology.

PubMed

Freeman, Scott; Haak, David; Wenderoth, Mary Pat

2011-01-01

We tested the hypothesis that highly structured course designs, which implement reading quizzes and/or extensive in-class active-learning activities and weekly practice exams, can lower failure rates in an introductory biology course for majors, compared with low-structure course designs that are based on lecturing and a few high-risk assessments. We controlled for 1) instructor effects by analyzing data from quarters when the same instructor taught the course, 2) exam equivalence with new assessments called the Weighted Bloom's Index and Predicted Exam Score, and 3) student equivalence using a regression-based Predicted Grade. We also tested the hypothesis that points from reading quizzes, clicker questions, and other "practice" assessments in highly structured courses inflate grades and confound comparisons with low-structure course designs. We found no evidence that points from active-learning exercises inflate grades or reduce the impact of exams on final grades. When we controlled for variation in student ability, failure rates were lower in a moderately structured course design and were dramatically lower in a highly structured course design. This result supports the hypothesis that active-learning exercises can make students more skilled learners and help bridge the gap between poorly prepared students and their better-prepared peers.

Phase I and II Trial of Huanglian, A Novel Botanical Against Breast Cancer that Enhances Taxol Activity

DTIC Science & Technology

2004-10-01

than an equivalent concentration of its major component, berberine , suggesting that several components contribute to its anticancer effect. It was...specifications the huanglian extract must have 7 peaks, which are within 5 to 10% of the original composition, and the predominant berberine peak (peak...for huanglian, had the necessary 50% biological activity against the MKN-74 cells, and contained sufficient berberine (20.5% of total weight) that was

Comparison of growth, serum biochemistries and n–6 fatty acid metabolism in rats fed diets supplemented with high-gamma-linolenic acid safflower oil or borage oil for 90 days

PubMed Central

Tso, Patrick; Caldwell, Jody; Lee, Dana; Boivin, Gregory P.; DeMichele, Stephen J.

2015-01-01

Recently, steps have been taken to further developments toward increasing gamma-linolenic acid (GLA) concentration and lowering costs in plant seed oils using transgenic technology. Through identification and expression of a fungal delta-6 desaturase gene in the high linoleic acid safflower plant, the seeds from this genetic transformation produce oil with >40% GLA (high GLA safflower oil (HGSO)). The aim of the study was to compare the effects of feeding HGSO to a generally recognized as safe source of GLA, borage oil, in a 90 day safety study in rats. Weanling male and female Sprague–Dawley rats were fed a semi-synthetic, fat free, pelleted diet (AIN93G) supplemented with a 10% (wt/wt) oil blend containing HGSO or borage oil, with equivalent GLA levels. Results demonstrated that feeding diets containing HGSO or borage oil for 90 days had similar biologic effects with regard to growth characteristics, body composition, behavior, organ weight and histology, and parameters of hematology and serum biochemistries in both sexes. Metabolism of the primary n–6 fatty acids in plasma and organ phospholipids was similar, despite minor changes in females. We conclude that HGSO is biologically equivalent to borage oil and provides a safe alternative source of GLA in the diet. PMID:22265940

Comparison of growth, serum biochemistries and n-6 fatty acid metabolism in rats fed diets supplemented with high-gamma-linolenic acid safflower oil or borage oil for 90 days.

PubMed

Tso, Patrick; Caldwell, Jody; Lee, Dana; Boivin, Gregory P; DeMichele, Stephen J

2012-06-01

Recently, steps have been taken to further developments toward increasing gamma-linolenic acid (GLA) concentration and lowering costs in plant seed oils using transgenic technology. Through identification and expression of a fungal delta-6 desaturase gene in the high linoleic acid safflower plant, the seeds from this genetic transformation produce oil with >40% GLA (high GLA safflower oil (HGSO)). The aim of the study was to compare the effects of feeding HGSO to a generally recognized as safe source of GLA, borage oil, in a 90 day safety study in rats. Weanling male and female Sprague-Dawley rats were fed a semi-synthetic, fat free, pelleted diet (AIN93G) supplemented with a 10% (wt/wt) oil blend containing HGSO or borage oil, with equivalent GLA levels. Results demonstrated that feeding diets containing HGSO or borage oil for 90 days had similar biologic effects with regard to growth characteristics, body composition, behavior, organ weight and histology, and parameters of hematology and serum biochemistries in both sexes. Metabolism of the primary n-6 fatty acids in plasma and organ phospholipids was similar, despite minor changes in females. We conclude that HGSO is biologically equivalent to borage oil and provides a safe alternative source of GLA in the diet. Copyright © 2012 Elsevier Ltd. All rights reserved.

Electrical circuit modeling and analysis of microwave acoustic interaction with biological tissues.

PubMed

Gao, Fei; Zheng, Qian; Zheng, Yuanjin

2014-05-01

Numerical study of microwave imaging and microwave-induced thermoacoustic imaging utilizes finite difference time domain (FDTD) analysis for simulation of microwave and acoustic interaction with biological tissues, which is time consuming due to complex grid-segmentation and numerous calculations, not straightforward due to no analytical solution and physical explanation, and incompatible with hardware development requiring circuit simulator such as SPICE. In this paper, instead of conventional FDTD numerical simulation, an equivalent electrical circuit model is proposed to model the microwave acoustic interaction with biological tissues for fast simulation and quantitative analysis in both one and two dimensions (2D). The equivalent circuit of ideal point-like tissue for microwave-acoustic interaction is proposed including transmission line, voltage-controlled current source, envelop detector, and resistor-inductor-capacitor (RLC) network, to model the microwave scattering, thermal expansion, and acoustic generation. Based on which, two-port network of the point-like tissue is built and characterized using pseudo S-parameters and transducer gain. Two dimensional circuit network including acoustic scatterer and acoustic channel is also constructed to model the 2D spatial information and acoustic scattering effect in heterogeneous medium. Both FDTD simulation, circuit simulation, and experimental measurement are performed to compare the results in terms of time domain, frequency domain, and pseudo S-parameters characterization. 2D circuit network simulation is also performed under different scenarios including different sizes of tumors and the effect of acoustic scatterer. The proposed circuit model of microwave acoustic interaction with biological tissue could give good agreement with FDTD simulated and experimental measured results. The pseudo S-parameters and characteristic gain could globally evaluate the performance of tumor detection. The 2D circuit network enables the potential to combine the quasi-numerical simulation and circuit simulation in a uniform simulator for codesign and simulation of a microwave acoustic imaging system, bridging bioeffect study and hardware development seamlessly.

From Noise to Order: The Psychological Development of Knowledge and Phenocopy in Biology

ERIC Educational Resources Information Center

Piaget, Jean

1975-01-01

Shows that one of the most general processes in the development of cognitive structures consists in replacing exogenous knowledge by endogenous reconstructions that reconstitute the same forms but incorporate them into systems whose internal composition is a pre-requisite. Biologically equivalent process is discussed. (Author/AM)

10 CFR 33.15 - Requirements for the issuance of a Type C specific license of broad scope.

Code of Federal Regulations, 2011 CFR

2011-01-01

... bachelor level, or equivalent training and experience, in the physical or biological sciences or in..., radiation detection instrumentation, and biological hazards of exposure to radiation appropriate to the type... controls and provisions relating to procurement of byproduct material, procedures, record keeping, material...

In vivo evidence that N-oleoylglycine acts independently of its conversion to oleamide.

PubMed

Chaturvedi, Shalini; Driscoll, William J; Elliot, Brenda M; Faraday, Martha M; Grunberg, Neil E; Mueller, Gregory P

2006-12-01

Oleamide (cis-9-octadecenamide) is a member of an emerging class of lipid-signaling molecules, the primary fatty acid amides. A growing body of evidence indicates that oleamide mediates fundamental neurochemical processes including sleep, thermoregulation, and nociception. Nevertheless, the mechanism for oleamide biosynthesis remains unknown. The leading hypothesis holds that oleamide is synthesized from oleoylglycine via the actions of the peptide amidating enzyme, peptidylglycine alpha-amidating monooxygenase (PAM). The present study investigated this hypothesis using pharmacologic treatments, physiologic assessments, and measurements of serum oleamide levels using a newly developed enzyme-linked immunosorbant assay (ELISA). Oleamide and oleoylglycine both induced profound hypothermia and decreased locomotion, over equivalent dose ranges and time courses, whereas, closely related compounds, stearamide and oleic acid, were essentially without effect. While the biologic actions of oleamide and oleoylglycine were equivalent, the two compounds differed dramatically with respect to their effects on serum levels of oleamide. Oleamide administration (80mg/kg) elevated blood-borne oleamide by eight-fold, whereas, the same dose of oleoylglycine had no effect on circulating oleamide levels. In addition, pretreatment with the established PAM inhibitor, disulfiram, produced modest reductions in the hypothermic responses to both oleoylglycine and oleamide, suggesting that the effects of disulfiram were not mediated through inhibition of PAM and a resulting decrease in the formation of oleamide from oleoylglycine. Collectively, these findings raise the possibilities that: (1) oleoylglycine possesses biologic activity that is independent of its conversion to oleamide and (2) the increased availability of oleoylglycine as a potential substrate does not drive the biosynthesis of oleamide.

In Vivo Evidence that N-Oleoylglycine Acts Independently of Its Conversion to Oleamide

PubMed Central

Chaturvedi, Shalini; Driscoll, William J.; Elliot, Brenda M.; Faraday, Martha M.; Grunberg, Neil E.; Mueller, Gregory P.

2006-01-01

Oleamide (cis-9-octadecenamide) is a member of an emerging class of lipid-signaling molecules, the primary fatty acid amides. A growing body of evidence indicates that oleamide mediates fundamental neurochemical processes including sleep, thermoregulation, and nociception. Nevertheless, the mechanism for oleamide biosynthesis remains unknown. The leading hypothesis holds that oleamide is synthesized from oleoylglycine via the actions of the peptide amidating enzyme, peptidylglycine alpha amidating monooxygenase (PAM). The present study investigated this hypothesis using pharmacologic treatments, physiologic assessments, and measurements of serum oleamide levels using a newly development enzyme-linked immunosorbant assay (ELISA). Oleamide and oleoylglycine both induced profound hypothermia and decreased locomotion, over equivalent dose ranges and time courses, whereas, closely related compounds, stearamide and oleic acid, were essentially without effect. While the biologic actions of oleamide and oleoylglycine were equivalent, the two compounds differed dramatically with respect to their effects on serum levels of oleamide. Oleamide administration (80 mg/kg) elevated blood-borne oleamide by eight-fold, whereas, the same dose of oleoylglycine had no effect on circulating oleamide levels. In addition, pretreatment with the established PAM inhibitor, disulfiram, produced modest reductions in the hypothermic responses to both oleoylglycine and oleamide, suggesting that the effects of disulfiram were not mediated through inhibition of PAM and a resulting decrease in the formation of oleamide from oleoylglycine. Collectively, these findings raise the possibilities that: (1) oleoylglycine possesses biologic activity that is independent of its conversion to oleamide, and (2) the increased availability of oleoylglycine as a potential substrate does not drive the biosynthesis of oleamide. PMID:17085322

Measurements of the neutron dose equivalent for various radiation qualities, treatment machines and delivery techniques in radiation therapy

NASA Astrophysics Data System (ADS)

Hälg, R. A.; Besserer, J.; Boschung, M.; Mayer, S.; Lomax, A. J.; Schneider, U.

2014-05-01

In radiation therapy, high energy photon and proton beams cause the production of secondary neutrons. This leads to an unwanted dose contribution, which can be considerable for tissues outside of the target volume regarding the long term health of cancer patients. Due to the high biological effectiveness of neutrons in regards to cancer induction, small neutron doses can be important. This study quantified the neutron doses for different radiation therapy modalities. Most of the reports in the literature used neutron dose measurements free in air or on the surface of phantoms to estimate the amount of neutron dose to the patient. In this study, dose measurements were performed in terms of neutron dose equivalent inside an anthropomorphic phantom. The neutron dose equivalent was determined using track etch detectors as a function of the distance to the isocenter, as well as for radiation sensitive organs. The dose distributions were compared with respect to treatment techniques (3D-conformal, volumetric modulated arc therapy and intensity-modulated radiation therapy for photons; spot scanning and passive scattering for protons), therapy machines (Varian, Elekta and Siemens linear accelerators) and radiation quality (photons and protons). The neutron dose equivalent varied between 0.002 and 3 mSv per treatment gray over all measurements. Only small differences were found when comparing treatment techniques, but substantial differences were observed between the linear accelerator models. The neutron dose equivalent for proton therapy was higher than for photons in general and in particular for double-scattered protons. The overall neutron dose equivalent measured in this study was an order of magnitude lower than the stray dose of a treatment using 6 MV photons, suggesting that the contribution of the secondary neutron dose equivalent to the integral dose of a radiotherapy patient is small.

Measurements of the neutron dose equivalent for various radiation qualities, treatment machines and delivery techniques in radiation therapy.

PubMed

Hälg, R A; Besserer, J; Boschung, M; Mayer, S; Lomax, A J; Schneider, U

2014-05-21

In radiation therapy, high energy photon and proton beams cause the production of secondary neutrons. This leads to an unwanted dose contribution, which can be considerable for tissues outside of the target volume regarding the long term health of cancer patients. Due to the high biological effectiveness of neutrons in regards to cancer induction, small neutron doses can be important. This study quantified the neutron doses for different radiation therapy modalities. Most of the reports in the literature used neutron dose measurements free in air or on the surface of phantoms to estimate the amount of neutron dose to the patient. In this study, dose measurements were performed in terms of neutron dose equivalent inside an anthropomorphic phantom. The neutron dose equivalent was determined using track etch detectors as a function of the distance to the isocenter, as well as for radiation sensitive organs. The dose distributions were compared with respect to treatment techniques (3D-conformal, volumetric modulated arc therapy and intensity-modulated radiation therapy for photons; spot scanning and passive scattering for protons), therapy machines (Varian, Elekta and Siemens linear accelerators) and radiation quality (photons and protons). The neutron dose equivalent varied between 0.002 and 3 mSv per treatment gray over all measurements. Only small differences were found when comparing treatment techniques, but substantial differences were observed between the linear accelerator models. The neutron dose equivalent for proton therapy was higher than for photons in general and in particular for double-scattered protons. The overall neutron dose equivalent measured in this study was an order of magnitude lower than the stray dose of a treatment using 6 MV photons, suggesting that the contribution of the secondary neutron dose equivalent to the integral dose of a radiotherapy patient is small.

Optimal design of clinical trials with biologics using dose-time-response models.

PubMed

Lange, Markus R; Schmidli, Heinz

2014-12-30

Biologics, in particular monoclonal antibodies, are important therapies in serious diseases such as cancer, psoriasis, multiple sclerosis, or rheumatoid arthritis. While most conventional drugs are given daily, the effect of monoclonal antibodies often lasts for months, and hence, these biologics require less frequent dosing. A good understanding of the time-changing effect of the biologic for different doses is needed to determine both an adequate dose and an appropriate time-interval between doses. Clinical trials provide data to estimate the dose-time-response relationship with semi-mechanistic nonlinear regression models. We investigate how to best choose the doses and corresponding sample size allocations in such clinical trials, so that the nonlinear dose-time-response model can be precisely estimated. We consider both local and conservative Bayesian D-optimality criteria for the design of clinical trials with biologics. For determining the optimal designs, computer-intensive numerical methods are needed, and we focus here on the particle swarm optimization algorithm. This metaheuristic optimizer has been successfully used in various areas but has only recently been applied in the optimal design context. The equivalence theorem is used to verify the optimality of the designs. The methodology is illustrated based on results from a clinical study in patients with gout, treated by a monoclonal antibody. Copyright © 2014 John Wiley & Sons, Ltd.

Equivalent formulations of “the equation of life”

NASA Astrophysics Data System (ADS)

Ao, Ping

2014-07-01

Motivated by progress in theoretical biology a recent proposal on a general and quantitative dynamical framework for nonequilibrium processes and dynamics of complex systems is briefly reviewed. It is nothing but the evolutionary process discovered by Charles Darwin and Alfred Wallace. Such general and structured dynamics may be tentatively named “the equation of life”. Three equivalent formulations are discussed, and it is also pointed out that such a quantitative dynamical framework leads naturally to the powerful Boltzmann-Gibbs distribution and the second law in physics. In this way, the equation of life provides a logically consistent foundation for thermodynamics. This view clarifies a particular outstanding problem and further suggests a unifying principle for physics and biology.

A proposal for the classification of biological weapons sensu lato.

PubMed

Rozsa, Lajos

2014-12-01

Due to historical and legislation reasons, the category of bioweapons is rather poorly defined. Authors often disagree on involving or excluding agents like hormones, psychochemicals, certain plants and animals (such as weeds or pests) or synthetic organisms. Applying a wide definition apparently threatens by eroding the regime of international legislation, while narrow definitions abandon several important issues. Therefore, I propose a category of 'biological weapons sensu lato' (BWsl) that is defined here as any tool of human aggression whose acting principle is based on disciplines of biology including particularly microbiology, epidemiology, medical biology, physiology, psychology, pharmacology and ecology, but excluding those based on inorganic agents. Synthetically produced equivalents (not necessarily exact copies) and mock weapons are also included. This definition does not involve any claim to subject all these weapons to international legislation but serves a purely scholarly purpose. BWsl may be properly categorized on the base of the magnitude of the human population potentially targeted (4 levels: individuals, towns, countries, global) and the biological nature of the weapons' intended effects (4 levels: agricultural-ecological agents, and non-pathogenic, pathogenic, or lethal agents against humans).

Macroscopic Quantum-Type Potentials in Theoretical Systems Biology

PubMed Central

Nottale, Laurent

2014-01-01

We review in this paper the use of the theory of scale relativity and fractal space-time as a tool particularly well adapted to the possible development of a future genuine systems theoretical biology. We emphasize in particular the concept of quantum-type potentials, since, in many situations, the effect of the fractality of space—or of the underlying medium—can be reduced to the addition of such a potential energy to the classical equations of motion. Various equivalent representations—geodesic, quantum-like, fluid mechanical, stochastic—of these equations are given, as well as several forms of generalized quantum potentials. Examples of their possible intervention in high critical temperature superconductivity and in turbulence are also described, since some biological processes may be similar in some aspects to these physical phenomena. These potential extra energy contributions could have emerged in biology from the very fractal nature of the medium, or from an evolutive advantage, since they involve spontaneous properties of self-organization, morphogenesis, structuration and multi-scale integration. Finally, some examples of applications of the theory to actual biological-like processes and functions are also provided. PMID:24709901

Neutron relative biological effectiveness in Hiroshima and Nagasaki atomic bomb survivors: a critical review

PubMed Central

Sasaki, Masao S.; Endo, Satoru; Hoshi, Masaharu; Nomura, Taisei

2016-01-01

The calculated risk of cancer in humans due to radiation exposure is based primarily on long-term follow-up studies, e.g. the life-span study (LSS) on atomic bomb (A-bomb) survivors in Hiroshima and Nagasaki. Since A-bomb radiation consists of a mixture of γ-rays and neutrons, it is essential that the relative biological effectiveness (RBE) of neutrons is adequately evaluated if a study is to serve as a reference for cancer risk. However, the relatively small neutron component hampered the direct estimation of RBE in LSS data. To circumvent this problem, several strategies have been attempted, including dose-independent constant RBE, dose-dependent variable RBE, and dependence on the degrees of dominance of intermingled γ-rays. By surveying the available literature, we tested the chromosomal RBE of neutrons as the biological endpoint for its equivalence to the microdosimetric quantities obtained using a tissue-equivalent proportional counter (TEPC) in various neutron fields. The radiation weighting factor, or quality factor, Qn, of neutrons as expressed in terms of the energy dependence of the maximum RBE, RBEm, was consistent with that predicted by the TEPC data, indicating that the chromosomally measured RBE was independent of the magnitude of coexisting γ-rays. The obtained neutron RBE, which varied with neutron dose, was confirmed to be the most adequate RBE system in terms of agreement with the cancer incidence in A-bomb survivors, using chromosome aberrations as surrogate markers. With this RBE system, the cancer risk in A-bomb survivors as expressed in unit dose of reference radiation is equally compatible with Hiroshima and Nagasaki cities, and may be potentially applicable in other cases of human radiation exposure. PMID:27614201

Biosimilars: Company Strategies to Capture Value from the Biologics Market

PubMed Central

Calo-Fernández, Bruno; Martínez-Hurtado, Juan Leonardo

2012-01-01

Patents for several biologic blockbusters will expire in the next few years. The arrival of biosimilars, the biologic equivalent of chemical generics, will have an impact on the current biopharmaceuticals market. Five core capabilities have been identified as paramount for those companies aiming to enter the biosimilars market: research and development, manufacturing, supporting activities, marketing, and lobbying. Understanding the importance of each of these capabilities will be key to maximising the value generated from the biologics patent cliff. PMID:24281342

Rheological and molecular weight comparisons of approved hyaluronic acid products - preliminary standards for establishing class III medical device equivalence.

PubMed

Braithwaite, Gavin J C; Daley, Michael J; Toledo-Velasquez, David

2016-01-01

Hyaluronic acid of various molecular weights has been in use for the treatment of osteoarthritis knee pain for decades. Worldwide, these products are regulated as either as drugs or devices and in some countries as both. In the US, this class of products is regulated as Class III medical devices, which places specific regulatory requirements on developers of these materials under a Pre-Market Approval process, typically requiring data from prospective randomized controlled clinical studies. In 1984 pharmaceutical manufacturers became able to file an Abbreviated New Drug Application for approval of a generic drug, thus establishing standards for demonstrating equivalence to an existing chemical entity. Recently, the first biosimilar, or 'generic biologic', was approved. Biosimilars are biological products that are approved by the FDA because they are 'highly similar' to a reference product, and have been shown to have no clinically meaningful differences from the reference product. For devices, Class II medical devices have a pathway for declaring equivalence to an existing product by filing a 510 k application for FDA clearance. However, until recently no equivalent regulatory pathway was available to Class III devices. In this paper, we consider the critical mechanical performance parameters for intra-articular hyaluronic products to demonstrate indistinguishable characteristics. Analogous to the aforementioned pathways that allow for a demonstration of equivalence, we examine these parameters for an existing, marketed device and compare molecular weight and rheological properties of multiple batches of a similar product. We propose that this establishes a scientific rationale for establishing Class III medical device equivalence.

Biological effectiveness of nuclear fragments produced by high-energy protons interacting in tissues near the bone- soft tissue interface

NASA Astrophysics Data System (ADS)

Shavers, Mark Randall

1999-12-01

High-energy protons in the galactic cosmic rays (GCR)-or generated by nuclear interactions of GCR heavy-ions with material-are capable of penetrating great thicknesses of shielding to irradiate humans in spacecraft or in lunar or Martian habitats. As protons interact with the nuclei of the elemental constituents of soft tissue and bone, low energy nuclei-target fragments-are emitted into the cells responsible for bone development and maintenance and for hematopoiesis. Leukemogenesis is the principal endpoint of concern because it is the most likely deleterious effect, and it has a short latency period and comparatively low survival rate, although other myelo- proliferative disorders and osteosarcoma also may be induced. A one-dimensional proton-target fragment transport model was used to calculate the energy spectra of fragments produced in bone and soft tissue, and present in marrow cavities at distances from a bone interface. In terms of dose equivalent, the target fragments are as significant as the incident protons. An average radiation quality factor was found to be between 1.8 and 2.6. Biological response to the highly non- uniform energy deposition of the target fragments is such that an alternative approach to conventional predictive risk assessment is needed. Alternative procedures are presented. In vitro cell response and relative biological effectiveness were calculated from the radial dose distribution of each fragment produced by 1-GeV protons using parameters of a modified Ion-Gamma- Kill (IGK) model of radiation action. The modelled endpoints were survival of C3H10t 1/2 and V79 cells, neoplastic transformation of C3H10t1/2 cells, and mutation of the X-linked hypoxanthine phosphoribosyltransferase (HPRT) locus in V79 cells. The dose equivalent and cell responses increased by 10% or less near the interface. Since RBE increases with decreasing dose in the IGK model, comparisons with quality factors were made at dose levels 0.01 <= D [Gy] <= 2. Applying average quality factors derived herein to GCR exposures results in a <= 5% increase of in average quality. Calculated RBEs indicate that accepted quality factors for high-energy protons may be too low due to the relatively high effectiveness of the low-charged target fragments. Derived RBEs for target fragments increase the calculated biological effectiveness of GCR by 20% to 180%.

Long-term primary culture of mouse mammary tumor cells: production of virus.

PubMed

Young, L J; Cardiff, R D; Ashley, R L

1975-05-01

Long-term primary cultures of mouse mammary tumor cells proved an excellent source of mouse mammary tumor virus (MMTV). Virus purified from these primary cultures had the same morphologic biochemical, immunologic, and biologic characteristics as MMTV. Quantitation of MMTV-protein equivalents released into the medium was measured by the radioimmunoassay for MMTV. Peak production levels were 20-40 mug MMTV protien equivalents/75-cm-2 flask/24 hours. These cultures produced MMTV for as long as 90 days. MMTV cultivation depended on the initial cell-plating density and hormones. Maximal MMTV release was obtained at a plating density of 1 times 10-6 cells/cm-2 in the presence of insulin and hydrocortisone. Insulin alone gave basal levels of MMTV, and hydrocortisone alone increased MMTV release only three-fold, but insulin and hydrocortisone together effected an eightfold increase in MMTV release. This suggested that hydrocortisone had a primary effect on MMTV release and insulin acted synergistically with hydrocortisone to maximize MMTV release.

2,3,7,8-tetrachlorodibenzo-p-dioxin equivalents in extracts of Baltic white-tailed sea eagles

DOE Office of Scientific and Technical Information (OSTI.GOV)

Koistinen, J.; Giesy, J.P.; Koivusaari, J.

Concentrations of 2,3,7,8-tetrachlorodibenzo-p-dioxin-(TCDD) equivalents were measured in extracts of Baltic white-tailed sea eagle tissues. Extracts of salmon, ringed seal, and grey seal were analyzed as other predatory species of the same area. Concentrations in eagle and seal tissues were greater than those in salmon. Concentrations of TCDD equivalents (TCDD-EQs) determined by the H4IIE bioassay were compared with toxic equivalents (TEQs) derived from instrumental chemical analyses in fractions containing polychlorinated dibenzo-P-dioxins and polychlorinated dibenzofurans (PCDD/PCDF) or coplanar polychlorinated biphenyls (PCBs). Toxic equivalents were calculated by use of an additive model in which the product of the concentrations of instrumentally measured individualmore » congeners were multiplied by their TCDD equivalency factors and were summed to give a total concentration of TEQs. The TCDD-EQs were compared with TEQs to develop a mass balance to determine whether all the TCDD-like activity was accounted for. The TEQs determined by chemical analyses for coplanar PCBs was 770 pg/g fw, and that of PCDD/PCDFs was 270 pg/g fw in this eagle. Thus, concentrations of TCDD-EQs were approx. 20% greater than those of TEQs. The true difference in activities is probably greater because of lower recoveries and infra-additivities among congeners in the bioassay. This indicates that there are compounds present in the extracts that can contribute to the total concentrations of TCDD-EQs in white-tailed sea eagle eggs to the no-observable-adverse-effect concentration, ranged from 7.3 to 141. This indicates that current concentrations of TCDD-EQs in these eggs are likely causing adverse effects in the Baltic populations of white-tailed sea eagles. This study indicated that the H4IIE bioassay is useful for monitoring the presence and biological activity of TCDD-like compounds in environmental samples like white-tailed sea eagles.« less

Shot sequencing based on biological equivalent dose considerations for multiple isocenter Gamma Knife radiosurgery

NASA Astrophysics Data System (ADS)

Ma, Lijun; Lee, Letitia; Barani, Igor; Hwang, Andrew; Fogh, Shannon; Nakamura, Jean; McDermott, Michael; Sneed, Penny; Larson, David A.; Sahgal, Arjun

2011-11-01

Rapid delivery of multiple shots or isocenters is one of the hallmarks of Gamma Knife radiosurgery. In this study, we investigated whether the temporal order of shots delivered with Gamma Knife Perfexion would significantly influence the biological equivalent dose for complex multi-isocenter treatments. Twenty single-target cases were selected for analysis. For each case, 3D dose matrices of individual shots were extracted and single-fraction equivalent uniform dose (sEUD) values were determined for all possible shot delivery sequences, corresponding to different patterns of temporal dose delivery within the target. We found significant variations in the sEUD values among these sequences exceeding 15% for certain cases. However, the sequences for the actual treatment delivery were found to agree (<3%) and to correlate (R2 = 0.98) excellently with the sequences yielding the maximum sEUD values for all studied cases. This result is applicable for both fast and slow growing tumors with α/β values of 2 to 20 according to the linear-quadratic model. In conclusion, despite large potential variations in different shot sequences for multi-isocenter Gamma Knife treatments, current clinical delivery sequences exhibited consistent biological target dosing that approached that maximally achievable for all studied cases.

Comparison of lactate, formate, and propionate as hydrogen donors for the reductive dehalogenation of trichloroethene in a continuous-flow column.

PubMed

Azizian, Mohammad F; Marshall, Ian P G; Behrens, Sebastian; Spormann, Alfred M; Semprini, Lewis

2010-04-01

A continuous-flow column study was conducted to analyze the reductive dehalogenation of trichloroethene (TCE) with aquifer material with high content of iron oxides. The column was bioaugmented with the Point Mugu (PM) culture, which is a mixed microbial enrichment culture capable of completely transforming TCE to ethene (ETH). We determined whether lactate, formate, or propionate fermentation resulted in more effective dehalogenation. Reductive dehalogenation, fermentation, and sulfate, Fe(III), and Mn(IV) reduction were all exhibited within the column. Different steady-states of dehalogenation were achieved based on the concentration of substrates added, with effective transformation to ETH obtained when ample electron donor equivalents were provided. Most of the metabolic reducing equivalents were channeled to sulfate, Fe(III), and Mn(IV) reduction. When similar electron reducing equivalents were added, the most effective dehalogenation was achieved with formate, with 14% of the electron equivalents going towards dehalogenation reactions, compared to 6.5% for lactate and 9.6% for propionate. Effective dehalogenation was maintained over 1000 days of column operation. Over 90% of electron equivalents added could be accounted for by the different electron accepting processes in the column, with 50% associated with soluble and precipitated Fe(II) and Mn(II). Bulk Fe(III) and Mn(IV) reduction was rather associated with lactate and propionate addition than formate addition. Sulfate reduction was a competing electron acceptor reaction with all three electron donors. DNA was extracted from solid coupon samples obtained during the course of the experiment and analyzed using 16S rRNA gene clone libraries and quantitative PCR. Lactate and propionate addition resulted in a significant increase in Geobacter, Spirochaetes, and Desulfitobacterium phylotypes relative to "Dehalococcoides" when compared to formate addition. Results from the molecular biological analyses support chemical observations that a greater percentage of the electron donor addition was channeled to Fe(III) reduction when lactate and propionate were added compared to formate, and formate was more effective than lactate in supporting dehalogenation. The results demonstrate the importance of electron donor selection and competing electron acceptor reactions when implementing reductive dehalogenation remediation technologies. Published by Elsevier B.V.

Comparison of lactate, formate, and propionate as hydrogen donors for the reductive dehalogenation of trichloroethene in a continuous-flow column

NASA Astrophysics Data System (ADS)

Azizian, Mohammad F.; Marshall, Ian P. G.; Behrens, Sebastian; Spormann, Alfred M.; Semprini, Lewis

2010-04-01

A continuous-flow column study was conducted to analyze the reductive dehalogenation of trichloroethene (TCE) with aquifer material with high content of iron oxides. The column was bioaugmented with the Point Mugu (PM) culture, which is a mixed microbial enrichment culture capable of completely transforming TCE to ethene (ETH). We determined whether lactate, formate, or propionate fermentation resulted in more effective dehalogenation. Reductive dehalogenation, fermentation, and sulfate, Fe(III), and Mn(IV) reduction were all exhibited within the column. Different steady-states of dehalogenation were achieved based on the concentration of substrates added, with effective transformation to ETH obtained when ample electron donor equivalents were provided. Most of the metabolic reducing equivalents were channeled to sulfate, Fe(III), and Mn(IV) reduction. When similar electron reducing equivalents were added, the most effective dehalogenation was achieved with formate, with 14% of the electron equivalents going towards dehalogenation reactions, compared to 6.5% for lactate and 9.6% for propionate. Effective dehalogenation was maintained over 1000 days of column operation. Over 90% of electron equivalents added could be accounted for by the different electron accepting processes in the column, with 50% associated with soluble and precipitated Fe(II) and Mn(II). Bulk Fe(III) and Mn(IV) reduction was rather associated with lactate and propionate addition than formate addition. Sulfate reduction was a competing electron acceptor reaction with all three electron donors. DNA was extracted from solid coupon samples obtained during the course of the experiment and analyzed using 16S rRNA gene clone libraries and quantitative PCR. Lactate and propionate addition resulted in a significant increase in Geobacter, Spirochaetes, and Desulfitobacterium phylotypes relative to " Dehalococcoides" when compared to formate addition. Results from the molecular biological analyses support chemical observations that a greater percentage of the electron donor addition was channeled to Fe(III) reduction when lactate and propionate were added compared to formate, and formate was more effective than lactate in supporting dehalogenation. The results demonstrate the importance of electron donor selection and competing electron acceptor reactions when implementing reductive dehalogenation remediation technologies.

Does incineration turn infectious waste aseptic?

PubMed

Kanemitsu, K; Inden, K; Kunishima, H; Ueno, K; Hatta, M; Gunji, Y; Watanabe, I; Kaku, M

2005-08-01

Incineration of infectious waste is considered to be biologically safe. We performed basic experiments to confirm that bacillus spores are killed by incineration in a muffle furnace. Biological samples containing 10(6) spores of Bacillus stearothermophilus were placed in stainless steel Petri dishes and then into hot furnaces. The furnace temperature and duration of incineration were 300 degrees C for 15 min, 300 degrees C for 30 min, 500 degrees C for 15 min, 500 degrees C for 30 min and 1100 degrees C for 3 min. We confirmed that all spores of B. stearothermophilus were killed at each of these settings. The effect of incineration seems to be equivalent to that of sterilization, based on the satisfactory sterilization assurance level of 10(-6).

Environmental Consequences of Invasive Species: Greenhouse Gas Emissions of Insecticide Use and the Role of Biological Control in Reducing Emissions

PubMed Central

Heimpel, George E.; Yang, Yi; Hill, Jason D.; Ragsdale, David W.

2013-01-01

Greenhouse gas emissions associated with pesticide applications against invasive species constitute an environmental cost of species invasions that has remained largely unrecognized. Here we calculate greenhouse gas emissions associated with the invasion of an agricultural pest from Asia to North America. The soybean aphid, Aphis glycines, was first discovered in North America in 2000, and has led to a substantial increase in insecticide use in soybeans. We estimate that the manufacture, transport, and application of insecticides against soybean aphid results in approximately 10.6 kg of carbon dioxide (CO2) equivalent greenhouse gasses being emitted per hectare of soybeans treated. Given the acreage sprayed, this has led to annual emissions of between 6 and 40 million kg of CO2 equivalent greenhouse gasses in the United States since the invasion of soybean aphid, depending on pest population size. Emissions would be higher were it not for the development of a threshold aphid density below which farmers are advised not to spray. Without a threshold, farmers tend to spray preemptively and the threshold allows farmers to take advantage of naturally occurring biological control of the soybean aphid, which can be substantial. We find that adoption of the soybean aphid economic threshold can lead to emission reductions of approximately 300 million kg of CO2 equivalent greenhouse gases per year in the United States. Previous studies have documented that biological control agents such as lady beetles are capable of suppressing aphid densities below this threshold in over half of the soybean acreage in the U.S. Given the acreages involved this suggests that biological control results in annual emission reductions of over 200 million kg of CO2 equivalents. These analyses show how interactions between invasive species and organisms that suppress them can interact to affect greenhouse gas emissions. PMID:23977273

Environmental consequences of invasive species: greenhouse gas emissions of insecticide use and the role of biological control in reducing emissions.

PubMed

Heimpel, George E; Yang, Yi; Hill, Jason D; Ragsdale, David W

2013-01-01

Greenhouse gas emissions associated with pesticide applications against invasive species constitute an environmental cost of species invasions that has remained largely unrecognized. Here we calculate greenhouse gas emissions associated with the invasion of an agricultural pest from Asia to North America. The soybean aphid, Aphis glycines, was first discovered in North America in 2000, and has led to a substantial increase in insecticide use in soybeans. We estimate that the manufacture, transport, and application of insecticides against soybean aphid results in approximately 10.6 kg of carbon dioxide (CO2) equivalent greenhouse gasses being emitted per hectare of soybeans treated. Given the acreage sprayed, this has led to annual emissions of between 6 and 40 million kg of CO2 equivalent greenhouse gasses in the United States since the invasion of soybean aphid, depending on pest population size. Emissions would be higher were it not for the development of a threshold aphid density below which farmers are advised not to spray. Without a threshold, farmers tend to spray preemptively and the threshold allows farmers to take advantage of naturally occurring biological control of the soybean aphid, which can be substantial. We find that adoption of the soybean aphid economic threshold can lead to emission reductions of approximately 300 million kg of CO2 equivalent greenhouse gases per year in the United States. Previous studies have documented that biological control agents such as lady beetles are capable of suppressing aphid densities below this threshold in over half of the soybean acreage in the U.S. Given the acreages involved this suggests that biological control results in annual emission reductions of over 200 million kg of CO2 equivalents. These analyses show how interactions between invasive species and organisms that suppress them can interact to affect greenhouse gas emissions.

42 CFR 493.1406 - Standard; Laboratory director qualifications on or before February 28, 1992.

Code of Federal Regulations, 2014 CFR

2014-10-01

... American Society of Cytology to practice cytopathology or possesses qualifications that are equivalent to... biological science as a major subject and (i) Is certified by the American Board of Medical Microbiology, the... master's degree from an accredited institution with a chemical, physical, or biological science as a...

42 CFR 493.1406 - Standard; Laboratory director qualifications on or before February 28, 1992.

Code of Federal Regulations, 2010 CFR

2010-10-01

... American Society of Cytology to practice cytopathology or possesses qualifications that are equivalent to... biological science as a major subject and (i) Is certified by the American Board of Medical Microbiology, the... master's degree from an accredited institution with a chemical, physical, or biological science as a...

42 CFR 493.1406 - Standard; Laboratory director qualifications on or before February 28, 1992.

Code of Federal Regulations, 2011 CFR

2011-10-01

... American Society of Cytology to practice cytopathology or possesses qualifications that are equivalent to... biological science as a major subject and (i) Is certified by the American Board of Medical Microbiology, the... master's degree from an accredited institution with a chemical, physical, or biological science as a...

42 CFR 493.1406 - Standard; Laboratory director qualifications on or before February 28, 1992.

Code of Federal Regulations, 2013 CFR

2013-10-01

... American Society of Cytology to practice cytopathology or possesses qualifications that are equivalent to... biological science as a major subject and (i) Is certified by the American Board of Medical Microbiology, the... master's degree from an accredited institution with a chemical, physical, or biological science as a...

42 CFR 493.1406 - Standard; Laboratory director qualifications on or before February 28, 1992.

Code of Federal Regulations, 2012 CFR

2012-10-01

... American Society of Cytology to practice cytopathology or possesses qualifications that are equivalent to... biological science as a major subject and (i) Is certified by the American Board of Medical Microbiology, the... master's degree from an accredited institution with a chemical, physical, or biological science as a...

What’s New in Enzymatic Halogenations

PubMed Central

Fujimori, Danica Galoniæ; Walsh, Christopher T.

2007-01-01

Summary The halogenation of thousands of natural products occurs during biosynthesis and often confers important functional properties. While haloperoxidases had been the default paradigm for enzymatic incorporation of halogens, via X+ equivalents into organic scaffolds, a combination of microbial genome sequencing, enzymatic studies and structural biology have provided deep new insights into enzymatic transfer of halide equivalents in three oxidation states. These are: (1) the halide ions (X−) abundant in nature, (2) halogen atoms (X•), and (3) the X+ equivalents. The mechanism of halogen incorporation is tailored to the electronic demands of specific substrates and involves enzymes with distinct redox coenzyme requirements. PMID:17881282

Effect of baking and frying on the in vivo toxicity to rats of cornmeal containing fumonisins.

PubMed

Voss, Kenneth A; Meredith, Filmore I; Bacon, Charles W

2003-08-27

Fumonisins are mycotoxins produced by Fusarium verticillioides (=F. moniliforme) and other Fusarium species. They are found in corn and corn-based foods. Cooking decreases fumonisin concentrations in food products under some conditions; however, little is known about how cooking effects biological activity. Baked cornbread, pan-fried corncakes, and deep-fried fritters were made from cornmeal that was spiked with 5% w/w F. verticillioides culture material (CM). The cooked materials and the uncooked CM-spiked cornmeal were fed to male rats (n = 5/group) for 2 weeks at high (20% w/w spiked cornmeal equivalents) or low (2% w/w spiked cornmeal equivalents) doses. A control group was fed a diet containing 20% w/w unspiked cornmeal. Toxic response to the uncooked CM-spiked cornmeal and the cooked products included decreased body weight gain (high-dose only), decreased kidney weight, and microscopic kidney and liver lesions of the type caused by fumonisins. Fumonisin concentration, as determined by HPLC analysis, in the 20% w/w pan-fried corncake diet [92.2 ppm of fumonisin B(1) (FB(1))] was slightly, but not statistically significantly, lower than those of the 20% w/w baked cornbread (132.2 ppm of FB(1)), deep-fried fritter (120.2 ppm of FB(1)) and CM-spiked cornmeal (130.5 of ppm FB(1)) diets. Therefore, baking and frying had no significant effect on the biological activity or concentration of fumonisins in these corn-based products, and the results provided no evidence for the formation of novel toxins or "hidden" fumonisins during cooking.

Improving Project Performance through Implementation of Agile Methodologies in the Renewable Energy Construction Industry

NASA Astrophysics Data System (ADS)

Hernandez Mendez, Arturo

Collaborative inquiry within undergraduate research experiences (UREs) is an effective curriculum tool to support student growth. This study seeks to understand how collaborative inquiry within undergraduate biology student experiences are affected within faculty mentored experiences and non-mentored experiences at a large private southeastern university. Undergraduate biology students engaged in UREs (faculty as mentor and non-mentor experiences) were examined for statistically significant differences in student self-efficacy. Self-efficacy was measured in three subcomponents (thinking and working like a scientist, scientific self-efficacy, and scientific identity) from student responses obtained in an online survey. Responses were analyzed using a nonparametric equivalent of a t test (Mann Whitney U test) to make comparisons between faculty mentored and non-mentored student groups. The conclusions of this study highlight the statistically significant effect of faculty mentoring in all three subcomponents. Faculty and university policy makers can apply these findings to develop further support for effective faculty mentoring practices in UREs.

Parents' willingness to pay for biologic treatments in juvenile idiopathic arthritis.

PubMed

Burnett, Heather F; Ungar, Wendy J; Regier, Dean A; Feldman, Brian M; Miller, Fiona A

2014-12-01

Biologic therapies are considered the standard of care for children with the most severe forms of juvenile idiopathic arthritis (JIA). Inconsistent and inadequate drug coverage, however, prevents many children from receiving timely and equitable access to the best treatment. The objective of this study was to evaluate parents' willingness to pay (WTP) for biologic and nonbiologic disease-modifying antirheumatic drugs (DMARDs) used to treat JIA. Utility weights from a discrete choice experiment were used to estimate the WTP for treatment characteristics including child-reported pain, participation in daily activities, side effects, days missed from school, drug treatment, and cost. Conditional logit regression was used to estimate utilities for each attribute level, and expected compensating variation was used to estimate the WTP. Bootstrapping was used to generate 95% confidence intervals for all WTP estimates. Parents had the highest marginal WTP for improved participation in daily activities and pain relief followed by the elimination of side effects of treatment. Parents were willing to pay $2080 (95% confidence interval $698-$4065) more for biologic DMARDs than for nonbiologic DMARDs if the biologic DMARD was more effective. Parents' WTP indicates their preference for treatments that reduce pain and improve daily functioning without side effects by estimating the monetary equivalent of utility for drug treatments in JIA. In addition to evidence of safety and efficacy, assessments of parents' preferences provide a broader perspective to decision makers by helping them understand the aspects of drug treatments in JIA that are most valued by families. Copyright © 2014 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

"SABER": A new software tool for radiotherapy treatment plan evaluation.

PubMed

Zhao, Bo; Joiner, Michael C; Orton, Colin G; Burmeister, Jay

2010-11-01

Both spatial and biological information are necessary in order to perform true optimization of a treatment plan and for predicting clinical outcome. The goal of this work is to develop an enhanced treatment plan evaluation tool which incorporates biological parameters and retains spatial dose information. A software system is developed which provides biological plan evaluation with a novel combination of features. It incorporates hyper-radiosensitivity using the induced-repair model and applies the new concept of dose convolution filter (DCF) to simulate dose wash-out effects due to cell migration, bystander effect, and/or tissue motion during treatment. Further, the concept of spatial DVH (sDVH) is introduced to evaluate and potentially optimize the spatial dose distribution in the target volume. Finally, generalized equivalent uniform dose is derived from both the physical dose distribution (gEUD) and the distribution of equivalent dose in 2 Gy fractions (gEUD2) and the software provides three separate models for calculation of tumor control probability (TCP), normal tissue complication probability (NTCP), and probability of uncomplicated tumor control (P+). TCP, NTCP, and P+ are provided as a function of prescribed dose and multivariable TCP, NTCP, and P+ plots are provided to illustrate the dependence on individual parameters used to calculate these quantities. Ten plans from two clinical treatment sites are selected to test the three calculation models provided by this software. By retaining both spatial and biological information about the dose distribution, the software is able to distinguish features of radiotherapy treatment plans not discernible using commercial systems. Plans that have similar DVHs may have different spatial and biological characteristics and the application of novel tools such as sDVH and DCF within the software may substantially change the apparent plan quality or predicted plan metrics such as TCP and NTCP. For the cases examined, both the calculation method and the application of DCF can change the ranking order of competing plans. The voxel-by-voxel TCP model makes it feasible to incorporate spatial variations of clonogen densities (n), radiosensitivities (SF2), and fractionation sensitivities (alpha/beta) as those data become available. The new software incorporates both spatial and biological information into the treatment planning process. The application of multiple methods for the incorporation of biological and spatial information has demonstrated that the order of application of biological models can change the order of plan ranking. Thus, the results of plan evaluation and optimization are dependent not only on the models used but also on the order in which they are applied. This software can help the planner choose more biologically optimal treatment plans and potentially predict treatment outcome more accurately.

Convex reformulation of biologically-based multi-criteria intensity-modulated radiation therapy optimization including fractionation effects

NASA Astrophysics Data System (ADS)

Hoffmann, Aswin L.; den Hertog, Dick; Siem, Alex Y. D.; Kaanders, Johannes H. A. M.; Huizenga, Henk

2008-11-01

Finding fluence maps for intensity-modulated radiation therapy (IMRT) can be formulated as a multi-criteria optimization problem for which Pareto optimal treatment plans exist. To account for the dose-per-fraction effect of fractionated IMRT, it is desirable to exploit radiobiological treatment plan evaluation criteria based on the linear-quadratic (LQ) cell survival model as a means to balance the radiation benefits and risks in terms of biologic response. Unfortunately, the LQ-model-based radiobiological criteria are nonconvex functions, which make the optimization problem hard to solve. We apply the framework proposed by Romeijn et al (2004 Phys. Med. Biol. 49 1991-2013) to find transformations of LQ-model-based radiobiological functions and establish conditions under which transformed functions result in equivalent convex criteria that do not change the set of Pareto optimal treatment plans. The functions analysed are: the LQ-Poisson-based model for tumour control probability (TCP) with and without inter-patient heterogeneity in radiation sensitivity, the LQ-Poisson-based relative seriality s-model for normal tissue complication probability (NTCP), the equivalent uniform dose (EUD) under the LQ-Poisson model and the fractionation-corrected Probit-based model for NTCP according to Lyman, Kutcher and Burman. These functions differ from those analysed before in that they cannot be decomposed into elementary EUD or generalized-EUD functions. In addition, we show that applying increasing and concave transformations to the convexified functions is beneficial for the piecewise approximation of the Pareto efficient frontier.

Arthroscopic Double-Row Transosseous Equivalent Rotator Cuff Repair with a Knotless Self-Reinforcing Technique.

PubMed

Mook, William R; Greenspoon, Joshua A; Millett, Peter J

2016-01-01

Rotator cuff tears are a significant cause of shoulder morbidity. Surgical techniques for repair have evolved to optimize the biologic and mechanical variables critical to tendon healing. Double-row repairs have demonstrated superior biomechanical advantages to a single-row. The preferred technique for rotator cuff repair of the senior author was reviewed and described in a step by step fashion. The final construct is a knotless double row transosseous equivalent construct. The described technique includes the advantages of a double-row construct while also offering self reinforcement, decreased risk of suture cut through, decreased risk of medial row overtensioning and tissue strangulation, improved vascularity, the efficiency of a knotless system, and no increased risk for subacromial impingement from the burden of suture knots. Arthroscopic knotless double row rotator cuff repair is a safe and effective method to repair rotator cuff tears.

Arthroscopic Double-Row Transosseous Equivalent Rotator Cuff Repair with a Knotless Self-Reinforcing Technique

PubMed Central

Mook, William R.; Greenspoon, Joshua A.; Millett, Peter J.

2016-01-01

Background: Rotator cuff tears are a significant cause of shoulder morbidity. Surgical techniques for repair have evolved to optimize the biologic and mechanical variables critical to tendon healing. Double-row repairs have demonstrated superior biomechanical advantages to a single-row. Methods: The preferred technique for rotator cuff repair of the senior author was reviewed and described in a step by step fashion. The final construct is a knotless double row transosseous equivalent construct. Results: The described technique includes the advantages of a double-row construct while also offering self reinforcement, decreased risk of suture cut through, decreased risk of medial row overtensioning and tissue strangulation, improved vascularity, the efficiency of a knotless system, and no increased risk for subacromial impingement from the burden of suture knots. Conclusion: Arthroscopic knotless double row rotator cuff repair is a safe and effective method to repair rotator cuff tears. PMID:27733881

Top-down causation by information control: from a philosophical problem to a scientific research programme

PubMed Central

Auletta, G; Ellis, G.F.R; Jaeger, L

2008-01-01

It has been claimed that different types of causes must be considered in biological systems, including top-down as well as same-level and bottom-up causation, thus enabling the top levels to be causally efficacious in their own right. To clarify this issue, the important distinctions between information and signs are introduced here and the concepts of information control and functional equivalence classes in those systems are rigorously defined and used to characterize when top-down causation by feedback control happens, in a way that is testable. The causally significant elements we consider are equivalence classes of lower level processes, realized in biological systems through different operations having the same outcome within the context of information control and networks. PMID:18319208

Novel detectors for silicon based microdosimetry, their concepts and applications

NASA Astrophysics Data System (ADS)

Rosenfeld, Anatoly B.

2016-02-01

This paper presents an overview of the development of semiconductor microdosimetry and the most current (state-of-the-art) Silicon on Insulator (SOI) detectors for microdosimetry based mainly on research and development carried out at the Centre for Medical Radiation Physics (CMRP) at the University of Wollongong with collaborators over the last 18 years. In this paper every generation of CMRP SOI microdosimeters, including their fabrication, design, and electrical and charge collection characterisation are presented. A study of SOI microdosimeters in various radiation fields has demonstrated that under appropriate geometrical scaling, the response of SOI detectors with the well-known geometry of microscopically sensitive volumes will record the energy deposition spectra representative of tissue cells of an equivalent shape. This development of SOI detectors for microdosimetry with increased complexity has improved the definition of microscopic sensitive volume (SV), which is modelling the deposition of ionising energy in a biological cell, that are led from planar to 3D SOI detectors with an array of segmented microscopic 3D SVs. The monolithic ΔE-E silicon telescope, which is an alternative to the SOI silicon microdosimeter, is presented, and as an example, applications of SOI detectors and ΔE-E monolithic telescope for microdosimetery in proton therapy field and equivalent neutron dose measurements out of field are also presented. An SOI microdosimeter "bridge" with 3D SVs can derive the relative biological effectiveness (RBE) in 12C ion radiation therapy that matches the tissue equivalent proportional counter (TEPC) quite well, but with outstanding spatial resolution. The use of SOI technology in experimental microdosimetry offers simplicity (no gas system or HV supply), high spatial resolution, low cost, high count rates, and the possibility of integrating the system onto a single device with other types of detectors.

Combined chemical and toxicological long-term monitoring for AhR agonists with SPMD-based virtual organisms in drinking water Danjiangkou Reservoir, China.

PubMed

Wang, Jingxian; Song, Guoqiang; Li, Aimin; Henkelmann, Bernhard; Pfister, Gerd; Tong, Anthony Z; Schramm, Karl-Werner

2014-08-01

SPMD-based virtual organisms (VOs) were employed for time-integrating, long-term sampling combined biological and chemical analyses for exposure assessment of hydrophobic organic pollutants (HOPs) in a drinking water reservoir, China. The SPMDs were deployed at four and five sites in the Danjiangkou (DJK) reservoir over two periods of 26 and 31 d to sequester the hydrophobic contaminants in water. The chosen bioassay response for the extracts of the SPMDs, the induction of 7-ethoxyresorufin-o-deethylase (EROD) was assayed using a rat hepatoma cell line (H4IIE). The known aryl hydrocarbon receptor (AhR) agonists PAHs and PCBs were analyzed by HRGC/HRMS instrument. The cause-effect relationship between the observed AhR activities and chemical concentrations of detected AhR agonists was examined. The results show that the extracts from the SPMD samples could induce AhR activity significantly, whereas the chemically derived 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) equivalent (TEQcal) was not correlated with the bioassay-derived TCDD equivalent (TEQbio). The known AhR agonists could only account for 2-10% of the observed AhR responses among which the contribution of PCBs could almost be neglected. Unidentified AhR-active compounds represented a greater proportion of the TCDD equivalent (TCDD-EQ) in SPMD samples from DJK. Based on the first assessment, the VO followed by the combination of chemical and biological analyses emerges as a resource efficient water monitoring device in ecotoxicological assessment for toxicologically relevant compounds which are readily available for uptake by resident aquatic biota in drinking water resources. Copyright © 2014 Elsevier Ltd. All rights reserved.

Neuroprotective Effects of Korean Red Pine(Pinus densiflora) Bark Extract and Its Phenolics.

PubMed

Kim, Ji-Won; Im, Sungbin; Jeong, Ha-Ram; Jung, Young-Seung; Lee, Inil; Kim, Kwan Joong; Park, Seung Kook; Kim, Dae-Ok

2018-03-15

Korean red pine ( Pinus densiflora ) is one of the major Pinus species in Korea. Red pine barkis removed prior to the chipping process in the wood industry and discarded aswaste. However, red pine bark contains a considerable amount of naturally occurring phenolics including flavonoids and therefore may have a variety of biological effects. In this study, we investigated if Korean red pine bark extract (KRPBE) could protect neuronal PC-12 cells from oxidative stress and inhibit cholinesterase activity.Analysis of reversed-phase high-performance liquid chromatography results revealed four phenolics in KRPBE:vanillin, protocatechuic acid, catechin and taxifolin.Total phenolic and flavonoid contents of KRPBE were 397.9 mg gallic acid equivalents/g dry weight (DW) and 248.7 mg catechin equivalents/g DW, respectively. Antioxidant capacities of KRPBE measured using ABTS, DPPH, and ORAC assays were 697.3, 521.8, and 2,627.7 mg vitamin C equivalents/g DW, respectively. KRPBE and its identified phenolics protected against H 2 O 2 -induced oxidative cell death in a dose-dependent manner. Acetylcholinesterase and butyrylcholinesterase, which degrade the neurotransmitter acetylcholine to terminate neurotransmission in synaptic clefts, were inhibited by treatment with KRPBE and its identified phenolics. Taken together, these results suggest that KRPBE and its constituent antioxidative phenolics are potent neuroprotective agents that can maintain cell viability in the context of oxidative stress and inhibit cholinesterase activity.

[Subchronic toxicity testing of mold-ripened cheese].

PubMed

Schoch, U; Lüthy, J; Schlatter, C

1984-08-01

The biological effects of known mycotoxins of Penicillium roqueforti or P. camemberti and other still unknown, but potentially toxic metabolites in mould ripened cheese (commercial samples of Blue- and Camembert cheese) were investigated. High amounts of mycelium (equivalents of 100 kg cheese/man and day) were fed to mice in a subchronic feeding trial. The following parameters were determined: development of body weight, organ weights, hematology, blood plasma enzymes. No signs of adverse effects produced by cheese mycotoxins could be detected after 28 days. No still unknown toxic metabolites could be demonstrated. From these results no health hazard from the consumption of mould ripened cheese, even in high amounts, appears to exist.

Effects of delayed mating on the reproductive biology of the vine mealybug, Planococcus ficus (Hemiptera: Pseudococcidae).

PubMed

Lentini, A; Mura, A; Muscas, E; Nuvoli, M T; Cocco, A

2018-04-01

The effect of increasing mating delay on the reproductive performance and population growth rates of the vine mealybug, Planococcus ficus (Signoret) (Hemiptera: Pseudococcidae), was investigated under laboratory conditions. Virgin females were mated at 1, 3, 5, 7, 14, 21 and 28 days after emergence and reproductive and life table parameters were estimated. The pre-oviposition period (number of days between mating and the onset of oviposition) significantly decreased in females mated within 7 days, whereas females mated at older ages showed equivalent pre-oviposition periods (7 days, as shorter delays in mating did not reduce the population growth rates.

Measurements of the neutron spectrum on the Martian surface with MSL/RAD

NASA Astrophysics Data System (ADS)

Köhler, J.; Zeitlin, C.; Ehresmann, B.; Wimmer-Schweingruber, R. F.; Hassler, D. M.; Reitz, G.; Brinza, D. E.; Weigle, G.; Appel, J.; Böttcher, S.; Böhm, E.; Burmeister, S.; Guo, J.; Martin, C.; Posner, A.; Rafkin, S.; Kortmann, O.

2014-03-01

The Radiation Assessment Detector (RAD), onboard the Mars Science Laboratory (MSL) rover Curiosity, measures the energetic charged and neutral particles and the radiation dose rate on the surface of Mars. An important factor for determining the biological impact of the Martian surface radiation is the specific contribution of neutrons, with their deeper penetration depth and ensuing high biological effectiveness. This is very difficult to measure quantitatively, resulting in considerable uncertainties in the total radiation dose. In contrast to charged particles, neutral particles (neutrons and gamma rays) are generally only measured indirectly. Measured spectra are a complex convolution of the incident particle spectrum with the detector response function and must be unfolded. We apply an inversion method (based on a maximum likelihood estimation) to calculate the neutron and gamma spectra from the RAD neutral particle measurements. Here we show the first spectra on the surface of Mars and compare them to theoretical predictions. The measured neutron spectrum (ranging from 8 to 740 MeV) translates into a radiation dose rate of 14±4μGy/d and a dose equivalent rate of 61±15μSv/d. This corresponds to 7% of the measured total surface dose rate and 10% of the biologically relevant surface dose equivalent rate on Mars. Measuring the Martian neutron and gamma spectra is an essential step for determining the mutagenic influences to past or present life at or beneath the Martian surface as well as the radiation hazard for future human exploration, including the shielding design of a potential habitat.

Equivalent Indels – Ambiguous Functional Classes and Redundancy in Databases

PubMed Central

Assmus, Jens; Kleffe, Jürgen; Schmitt, Armin O.; Brockmann, Gudrun A.

2013-01-01

There is considerable interest in studying sequenced variations. However, while the positions of substitutions are uniquely identifiable by sequence alignment, the location of insertions and deletions still poses problems. Each insertion and deletion causes a change of sequence. Yet, due to low complexity or repetitive sequence structures, the same indel can sometimes be annotated in different ways. Two indels which differ in allele sequence and position can be one and the same, i.e. the alternative sequence of the whole chromosome is identical in both cases and, therefore, the two deletions are biologically equivalent. In such a case, it is impossible to identify the exact position of an indel merely based on sequence alignment. Thus, variation entries in a mutation database are not necessarily uniquely defined. We prove the existence of a contiguous region around an indel in which all deletions of the same length are biologically identical. Databases often show only one of several possible locations for a given variation. Furthermore, different data base entries can represent equivalent variation events. We identified 1,045,590 such problematic entries of insertions and deletions out of 5,860,408 indel entries in the current human database of Ensembl. Equivalent indels are found in sequence regions of different functions like exons, introns or 5' and 3' UTRs. One and the same variation can be assigned to several different functional classifications of which only one is correct. We implemented an algorithm that determines for each indel database entry its complete set of equivalent indels which is uniquely characterized by the indel itself and a given interval of the reference sequence. PMID:23658777

21 CFR 640.65 - Plasmapheresis.

Code of Federal Regulations, 2012 CFR

2012-04-01

... quantitative immuno-diffusion test or an equivalent test to determine immunoglobulin composition of the plasma..., Center for Biologics Evaluation and Research, and collection shall not occur less than 2 days apart or...

21 CFR 640.65 - Plasmapheresis.

Code of Federal Regulations, 2014 CFR

2014-04-01

... quantitative immuno-diffusion test or an equivalent test to determine immunoglobulin composition of the plasma..., Center for Biologics Evaluation and Research, and collection shall not occur less than 2 days apart or...

21 CFR 640.65 - Plasmapheresis.

Code of Federal Regulations, 2013 CFR

2013-04-01

... quantitative immuno-diffusion test or an equivalent test to determine immunoglobulin composition of the plasma..., Center for Biologics Evaluation and Research, and collection shall not occur less than 2 days apart or...

21 CFR 640.65 - Plasmapheresis.

Code of Federal Regulations, 2011 CFR

2011-04-01

... quantitative immuno-diffusion test or an equivalent test to determine immunoglobulin composition of the plasma..., Center for Biologics Evaluation and Research, and collection shall not occur less than 2 days apart or...

21 CFR 640.65 - Plasmapheresis.

Code of Federal Regulations, 2010 CFR

2010-04-01

... quantitative immuno-diffusion test or an equivalent test to determine immunoglobulin composition of the plasma..., Center for Biologics Evaluation and Research, and collection shall not occur less than 2 days apart or...

Radioprotection of Intestinal Stem Cells and Whole Body Radiation Lethality from Photons and Neutrons by Prostaglandins along or in Combination with WR-2721

DTIC Science & Technology

1990-12-01

asthma, calcium metabolic defects, angina pectoris and peptic ulcer . As a result of the array and sometimes antagonistic biologic effects of the family of...Arlington, VA 22202-4302, and to the Office of Management and Budget. Paperwork Reduction Project (0704-0188). Washington. OC 20503 1, AGENCY USE ONLY (Leave... perforated plastic tubes that, in turn, were placed between two A-150 tissue equivalent disks for build-up and backscatter. The disks holding the mice were

Galactic cosmic ray transport methods and radiation quality issues

NASA Technical Reports Server (NTRS)

Townsend, L. W.; Wilson, J. W.; Cucinotta, F. A.; Shinn, J. L.

1992-01-01

An overview of galactic cosmic ray (GCR) interaction and transport methods, as implemented in the Langley Research Center GCR transport code, is presented. Representative results for solar minimum, exo-magnetospheric GCR dose equivalents in water are presented on a component by component basis for various thicknesses of aluminum shielding. The impact of proposed changes to the currently used quality factors on exposure estimates and shielding requirements are quantified. Using the cellular track model of Katz, estimates of relative biological effectiveness (RBE) for the mixed GCR radiation fields are also made.

The effect of abstract versus concrete framing on judgments of biological and psychological bases of behavior.

PubMed

Kim, Nancy S; Johnson, Samuel G B; Ahn, Woo-Kyoung; Knobe, Joshua

2017-01-01

Human behavior is frequently described both in abstract, general terms and in concrete, specific terms. We asked whether these two ways of framing equivalent behaviors shift the inferences people make about the biological and psychological bases of those behaviors. In five experiments, we manipulated whether behaviors are presented concretely (i.e. with reference to a specific person, instantiated in the particular context of that person's life) or abstractly (i.e. with reference to a category of people or behaviors across generalized contexts). People judged concretely framed behaviors to be less biologically based and, on some dimensions, more psychologically based than the same behaviors framed in the abstract. These findings held true for both mental disorders (Experiments 1 and 2) and everyday behaviors (Experiments 4 and 5), and yielded downstream consequences for the perceived efficacy of disorder treatments (Experiment 3). Implications for science educators, students of science, and members of the lay public are discussed.

Biophysical principles of regulatory action of low-intensity laser irradiation

NASA Astrophysics Data System (ADS)

Mostovnikov, Vasili A.; Mostovnikova, Galina R.; Plavski, Vitali Y.; Plavskaja, Ljudmila G.

1996-01-01

The investigations carried out in our group on biological systems of various organization level (enzyme molecules in solution, human and animal cell cultures), allowed us to conclude, that the light-induced changes of spatial structure of cells components form the basis of biological activity (and as a consequence therapeutic effect) of various wavelength low-intensity laser emission. Photophysical mechanism of these changes lies in the reorientation of highregulated anisotropic parts (domains) with the liquid-crystalline type of ordering of the cell components due to the interaction between the electric field and the light induced integral electric dipole of the domain. The mechanism of such reorientation is well established in physics of liquid crystals of nematic type and is known as light induced analogue of Frederix's effect. The following results enable us to draw the conclusion about the determining role of the orientations effects on the biological activity mechanism of low-intensity laser radiation: (1) the possibility of reversible modification of spatial structure and enzyme molecules functional activity under the influence of laser radiation outside the band of their own or admixture absorption; (2) the dependence of biological effect of laser radiation on the functional activity of cells vs. polarization degree of the light with the maximum photobiological effects observed for linear-polarized radiation; (3) the equivalence of a static magnetic field and low-intensity laser radiation in action on functional activity of the cells and the lowering of the laser field intensity for the achieving the definite changes of the cell functional activity in the presence of static magnetic field.

Intergenerational transmission of prejudice, sex role stereotyping, and intolerance.

PubMed

O'Bryan, Megan; Fishbein, Harold D; Ritchey, P Neal

2004-01-01

The attitudes of 111 ninth and eleventh graders and both of their biological parents were independently assessed for prejudice against people with HIV/ AIDS, homosexuals, Blacks, and fat people, as well as for male and female sex role stereotyping. This study corrected for two shortcomings in previous research: neglecting to assess both parents and assessing only a single domain of prejudice. We addressed the intergenerational transmission of prejudice and stereotyping using three competing models: same-sex, parent equivalent, and differential effects. Using multiple regressions in which parents' scores were entered separately, along with control variables, different maternal and paternal influences were detected. Mothers were the primary influence for prejudice regarding HIV/AIDS, fatness, and race, and fathers were the primary influence for male and female stereotyping and prejudice against homosexuals, supporting the differential effects model. We also established that prejudice and stereotyping in specific domains reflected a more general proclivity to be intolerant. In contrast to prejudice and stereotyping in specific domains, fathers and mothers about equally shaped the adolescents' intolerance, supporting the parent equivalent model.

Scope of claim coverage in patents of fufang Chinese herbal drugs: Substitution of ingredients

PubMed Central

2011-01-01

Herbal ingredients in a Chinese fufang prescription are often replaced by one or several other herbal combinations. As there have been very few Chinese herbal patent infringement cases, it is still unclear how the Doctrine of Equivalents should be applied to determine the scope of 'equivalents' in Chinese fufang prescriptions. Case law principles from cases in other technical areas such as chemical patents and biological drug patents can be borrowed to ascertain a precise scope of a fufang patent. This article summarizes and discusses several chemical and biopharmaceutical patent cases. In cases where a certain herbal ingredient is substituted by another herb or a combination of herbs, accused infringers are likely to relate herbal drug patents to chemical drug patents with strict interpretation whereas patent owners may take advantage of the liberal application of Doctrine of Equivalence in biopharmaceutical patents by analogizing the complex nature of herbal drugs with biological drugs. Therefore, consideration should be given to the purpose of an ingredient in a patent, the qualities when combined with the other ingredients and the intended function. The scope of equivalents also depends on the stage of the prior art. Moreover, it is desirable to disclose any potential substitutes when drafting the application. Claims should be drafted in such a way that all foreseeable modifications are encompassed for the protection of the patent owner's intellectual property. PMID:21854570

Scope of claim coverage in patents of fufang Chinese herbal drugs: Substitution of ingredients.

PubMed

Wang, Xinsheng; Tian, Jiaher; Chan, Albert Wai-Kit

2011-08-19

Herbal ingredients in a Chinese fufang prescription are often replaced by one or several other herbal combinations. As there have been very few Chinese herbal patent infringement cases, it is still unclear how the Doctrine of Equivalents should be applied to determine the scope of 'equivalents' in Chinese fufang prescriptions. Case law principles from cases in other technical areas such as chemical patents and biological drug patents can be borrowed to ascertain a precise scope of a fufang patent. This article summarizes and discusses several chemical and biopharmaceutical patent cases. In cases where a certain herbal ingredient is substituted by another herb or a combination of herbs, accused infringers are likely to relate herbal drug patents to chemical drug patents with strict interpretation whereas patent owners may take advantage of the liberal application of Doctrine of Equivalence in biopharmaceutical patents by analogizing the complex nature of herbal drugs with biological drugs. Therefore, consideration should be given to the purpose of an ingredient in a patent, the qualities when combined with the other ingredients and the intended function. The scope of equivalents also depends on the stage of the prior art. Moreover, it is desirable to disclose any potential substitutes when drafting the application. Claims should be drafted in such a way that all foreseeable modifications are encompassed for the protection of the patent owner's intellectual property.

A Phenolic Extract Obtained from Methyl Jasmonate-Treated Strawberries Enhances Apoptosis in a Human Cervical Cancer Cell Line.

PubMed

Spagnuolo, Carmela; Flores, Gema; Russo, Gian Luigi; Ruiz Del Castillo, Maria Luisa

2016-10-01

In the present study, we evaluated the effect of methyl jasmonate (MeJA) treatment on strawberry phenolic composition. Strawberry extracts contain a mixture of phenolic compounds possessing several biological properties. We demonstrated that these extracts were more effective in inducing apoptosis in HeLa cells compared to phenolic preparations derived from untreated strawberries. Treatment of strawberries with 0.5% MeJA resulted in increased polyphenols content (from 7.4 to 8.6 mM quercetin equivalents) and antioxidant properties (from 3.9 to 4.6 mM quercetin equivalents). The identification and quantification of phenolic compounds by liquid chromatography-mass spectrometry in the strawberry extracts showed that cyanidin glucoside, pelargonidin glucoside, and ellagic glucoside acid were significantly higher in strawberries treated with MeJA. Phenolic extracts from MeJA-treated strawberries significantly decreased the cell viability in HeLa cells, compared to extracts derived from untreated fruits. We hypothesized that the enhanced apoptotic activity of MeJA-treated strawberries was due to a synergistic or additive effect of different phenolic compounds present in the extract, rather than the activity of a single molecule.

The effects of small field dosimetry on the biological models used in evaluating IMRT dose distributions

NASA Astrophysics Data System (ADS)

Cardarelli, Gene A.

The primary goal in radiation oncology is to deliver lethal radiation doses to tumors, while minimizing dose to normal tissue. IMRT has the capability to increase the dose to the targets and decrease the dose to normal tissue, increasing local control, decrease toxicity and allow for effective dose escalation. This advanced technology does present complex dose distributions that are not easily verified. Furthermore, the dose inhomogeneity caused by non-uniform dose distributions seen in IMRT treatments has caused the development of biological models attempting to characterize the dose-volume effect in the response of organized tissues to radiation. Dosimetry of small fields can be quite challenging when measuring dose distributions for high-energy X-ray beams used in IMRT. The proper modeling of these small field distributions is essential in reproducing accurate dose for IMRT. This evaluation was conducted to quantify the effects of small field dosimetry on IMRT plan dose distributions and the effects on four biological model parameters. The four biological models evaluated were: (1) the generalized Equivalent Uniform Dose (gEUD), (2) the Tumor Control Probability (TCP), (3) the Normal Tissue Complication Probability (NTCP) and (4) the Probability of uncomplicated Tumor Control (P+). These models are used to estimate local control, survival, complications and uncomplicated tumor control. This investigation compares three distinct small field dose algorithms. Dose algorithms were created using film, small ion chamber, and a combination of ion chamber measurements and small field fitting parameters. Due to the nature of uncertainties in small field dosimetry and the dependence of biological models on dose volume information, this examination quantifies the effects of small field dosimetry techniques on radiobiological models and recommends pathways to reduce the errors in using these models to evaluate IMRT dose distributions. This study demonstrates the importance of valid physical dose modeling prior to the use of biological modeling. The success of using biological function data, such as hypoxia, in clinical IMRT planning will greatly benefit from the results of this study.

Biological effective dose evaluation in gynaecological brachytherapy: LDR and HDR treatments, dependence on radiobiological parameters, and treatment optimisation.

PubMed

Bianchi, C; Botta, F; Conte, L; Vanoli, P; Cerizza, L

2008-10-01

This study was undertaken to compare the biological efficacy of different high-dose-rate (HDR) and low-dose-rate (LDR) treatments of gynaecological lesions, to identify the causes of possible nonuniformity and to optimise treatment through customised calculation. The study considered 110 patients treated between 2001 and 2006 with external beam radiation therapy and/or brachytherapy with either LDR (afterloader Selectron, (137)Cs) or HDR (afterloader microSelectron Classic, (192)Ir). The treatments were compared in terms of biologically effective dose (BED) to the tumour and to the rectum (linear-quadratic model) by using statistical tests for comparisons between independent samples. The difference between the two treatments was statistically significant in one case only. However, within each technique, we identified considerable nonuniformity in therapeutic efficacy due to differences in fractionation schemes and overall treatment time. To solve this problem, we created a Microsoft Excel spreadsheet allowing calculation of the optimal treatment for each patient: best efficacy (BED(tumour)) without exceeding toxicity threshold (BED(rectum)). The efficacy of a treatment may vary as a result of several factors. Customised radiobiological evaluation is a useful adjunct to clinical evaluation in planning equivalent treatments that satisfy all dosimetric constraints.

Neutron relative biological effectiveness in Hiroshima and Nagasaki atomic bomb survivors: a critical review.

PubMed

Sasaki, Masao S; Endo, Satoru; Hoshi, Masaharu; Nomura, Taisei

2016-11-01

The calculated risk of cancer in humans due to radiation exposure is based primarily on long-term follow-up studies, e.g. the life-span study (LSS) on atomic bomb (A-bomb) survivors in Hiroshima and Nagasaki. Since A-bomb radiation consists of a mixture of γ-rays and neutrons, it is essential that the relative biological effectiveness (RBE) of neutrons is adequately evaluated if a study is to serve as a reference for cancer risk. However, the relatively small neutron component hampered the direct estimation of RBE in LSS data. To circumvent this problem, several strategies have been attempted, including dose-independent constant RBE, dose-dependent variable RBE, and dependence on the degrees of dominance of intermingled γ-rays. By surveying the available literature, we tested the chromosomal RBE of neutrons as the biological endpoint for its equivalence to the microdosimetric quantities obtained using a tissue-equivalent proportional counter (TEPC) in various neutron fields. The radiation weighting factor, or quality factor, Q n , of neutrons as expressed in terms of the energy dependence of the maximum RBE, RBE m , was consistent with that predicted by the TEPC data, indicating that the chromosomally measured RBE was independent of the magnitude of coexisting γ-rays. The obtained neutron RBE, which varied with neutron dose, was confirmed to be the most adequate RBE system in terms of agreement with the cancer incidence in A-bomb survivors, using chromosome aberrations as surrogate markers. With this RBE system, the cancer risk in A-bomb survivors as expressed in unit dose of reference radiation is equally compatible with Hiroshima and Nagasaki cities, and may be potentially applicable in other cases of human radiation exposure. © The Author 2016. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

75 FR 53271 - Application(s) for Duty-Free Entry of Scientific Instruments

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-31

... invite comments on the question of whether instruments of equivalent scientific value, for the purposes... structure of biological macromolecules, which will be observed under cryogenic conditions. Justification for...

77 FR 25960 - Application(s) for Duty-Free Entry of Scientific Instruments

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-02

... invite comments on the question of whether instruments of equivalent scientific value, for the purposes... imaging biological and other materials samples. Justification for Duty-Free Entry: There are no...

Effects of model structural uncertainty on carbon cycle projections: biological nitrogen fixation as a case study

NASA Astrophysics Data System (ADS)

Wieder, William R.; Cleveland, Cory C.; Lawrence, David M.; Bonan, Gordon B.

2015-04-01

Uncertainties in terrestrial carbon (C) cycle projections increase uncertainty of potential climate feedbacks. Efforts to improve model performance often include increased representation of biogeochemical processes, such as coupled carbon-nitrogen (N) cycles. In doing so, models are becoming more complex, generating structural uncertainties in model form that reflect incomplete knowledge of how to represent underlying processes. Here, we explore structural uncertainties associated with biological nitrogen fixation (BNF) and quantify their effects on C cycle projections. We find that alternative plausible structures to represent BNF result in nearly equivalent terrestrial C fluxes and pools through the twentieth century, but the strength of the terrestrial C sink varies by nearly a third (50 Pg C) by the end of the twenty-first century under a business-as-usual climate change scenario representative concentration pathway 8.5. These results indicate that actual uncertainty in future C cycle projections may be larger than previously estimated, and this uncertainty will limit C cycle projections until model structures can be evaluated and refined.

Chief, Structural Biophysics Laboratory | Center for Cancer Research

Cancer.gov

The SBL Chief is expected to establish a strong research program in structural biology/biophysics in addition to providing leadership of the SBL and the structural biology community in the NCI Intramural Program.  Applicants should hold a Ph.D., M.D./Ph.D., or equivalent doctoral degree in a relevant discipline, and should possess outstanding communication skills and documented leadership experience.  Tenured faculty or industrial scientists of equivalent rank with a demonstrated commitment to structural biophysics should apply.  Salary will be commensurate with experience and accomplishments.  This position is not restricted to U.S. citizens. A full civil service package of benefits (including health insurance, life insurance, and retirement) is available. This position is subject to a background investigation.  The NIH is dedicated to building a diverse community in its training and employment programs.

Towards physical principles of biological evolution

NASA Astrophysics Data System (ADS)

Katsnelson, Mikhail I.; Wolf, Yuri I.; Koonin, Eugene V.

2018-03-01

Biological systems reach organizational complexity that far exceeds the complexity of any known inanimate objects. Biological entities undoubtedly obey the laws of quantum physics and statistical mechanics. However, is modern physics sufficient to adequately describe, model and explain the evolution of biological complexity? Detailed parallels have been drawn between statistical thermodynamics and the population-genetic theory of biological evolution. Based on these parallels, we outline new perspectives on biological innovation and major transitions in evolution, and introduce a biological equivalent of thermodynamic potential that reflects the innovation propensity of an evolving population. Deep analogies have been suggested to also exist between the properties of biological entities and processes, and those of frustrated states in physics, such as glasses. Such systems are characterized by frustration whereby local state with minimal free energy conflict with the global minimum, resulting in ‘emergent phenomena’. We extend such analogies by examining frustration-type phenomena, such as conflicts between different levels of selection, in biological evolution. These frustration effects appear to drive the evolution of biological complexity. We further address evolution in multidimensional fitness landscapes from the point of view of percolation theory and suggest that percolation at level above the critical threshold dictates the tree-like evolution of complex organisms. Taken together, these multiple connections between fundamental processes in physics and biology imply that construction of a meaningful physical theory of biological evolution might not be a futile effort. However, it is unrealistic to expect that such a theory can be created in one scoop; if it ever comes to being, this can only happen through integration of multiple physical models of evolutionary processes. Furthermore, the existing framework of theoretical physics is unlikely to suffice for adequate modeling of the biological level of complexity, and new developments within physics itself are likely to be required.

Increased Phosphorus Uptake by Wheat and Field Beans Inoculated with a Phosphorus-Solubilizing Penicillium bilaji Strain and with Vesicular-Arbuscular Mycorrhizal Fungi.

PubMed

Kucey, R M

1987-12-01

Greenhouse and field experiments were conducted to test the effect of a P-solubilizing isolate of Penicillium bilaji on the availability of Idaho rock phosphate (RP) in a calcareous soil. Under controlled greenhouse conditions, inoculation of soils with P. bilaji along with RP at 45 mug of P per g of soil resulted in plant dry matter production and P uptake by wheat (Triticum aestivum) and beans (Phaseolus vulgaris) that were not significantly different from the increases in dry matter production and P uptake caused by the addition of 15 mug of P per g of soil as triple superphosphate. Addition of RP alone had no effect on plant growth. Addition of vesicular-arbuscular mycorrhizal fungi was necessary for maximum effect in the sterilized soil in the greenhouse experiment. Under field conditions, a treatment consisting of RP (20 kg of P per ha of soil) plus P. bilaji plus straw resulted in wheat yields and P uptake equivalent to increases due to the addition of monoammonium phosphate added at an equivalent rate of P. RP added alone had no effect on wheat growth or P uptake. The results indicate that a biological system of RP solubilization can be used to increase the availability of RP added to calcareous soils.

[Dosimetric system for assessing doses received by people occupationally exposed to external sources of ionizing radiation].

PubMed

Brodecki, Marcin; Domienik, Joanna U; Zmyślony, Marek

2012-01-01

The current system of dosimetric quantities has been defined by the International Commission on Radiological Protection (ICRP) and the International Commission on Radiation Units and Measurements (ICRU). Complexity of the system implies the physical nature of ionizing radiation, resulting from the presence of different types of radiation of different ionization capabilities, as well as the individual radiation sensitivity of biological material exposed. According to the latest recommendations, there are three types of dosimeter quantities relevant to radiation protection and radiological assessment of occupational exposure. These are the basic quantities, safety quantities and operational quantities. Dose limits for occupational exposure relate directly to the protection quantities, i.e. the equivalent dose and effective dose, while these quantities are practically unmeasurable in real measurement conditions. For this reason, in the system of dosimetric quantities directly measurable operating volumes were defined. They represent equivalents of the protection quantities that allow for a reliable assessment of equivalent and effective dose by conducting routine monitoring of occupational exposure. This paper presents the characteristics of these quantities, their relationships and importance in assessing individual effects of radiation. Also the methods for their implementation in personal and environmental dosimetry were showcased. The material contained in the article is a compendium of essential information about dosimetric quantities with reference to the contemporary requirements of the law, including the changed annual occupational exposure limit for the lens of the eye. The material is especially addressed to those responsible for dosimetry monitoring in the workplace, radiation protection inspectors and occupational health physicians.

Evaluation of the effect of prostate volume change on tumor control probability in LDR brachytherapy.

PubMed

Knaup, Courtney; Mavroidis, Panayiotis; Stathakis, Sotirios; Smith, Mark; Swanson, Gregory; Papanikolaou, Niko

2011-09-01

This study evaluates low dose-rate brachytherapy (LDR) prostate plans to determine the biological effect of dose degradation due to prostate volume changes. In this study, 39 patients were evaluated. Pre-implant prostate volume was determined using ultrasound. These images were used with the treatment planning system (Nucletron Spot Pro 3.1(®)) to create treatment plans using (103)Pd seeds. Following the implant, patients were imaged using CT for post-implant dosimetry. From the pre and post-implant DVHs, the biologically equivalent dose and the tumor control probability (TCP) were determined using the biologically effective uniform dose. The model used RBE = 1.75 and α/β = 2 Gy. The prostate volume changed between pre and post implant image sets ranged from -8% to 110%. TCP and the mean dose were reduced up to 21% and 56%, respectively. TCP is observed to decrease as the mean dose decreases to the prostate. The post-implant tumor dose was generally observed to decrease, compared to the planned dose. A critical uniform dose of 130 Gy was established. Below this dose, TCP begins to fall-off. It was also determined that patients with a small prostates were more likely to suffer TCP decrease. The biological effect of post operative prostate growth due to operative trauma in LDR was evaluated using the concept. The post-implant dose was lower than the planned dose due to an increase of prostate volume post-implant. A critical uniform dose of 130 Gy was determined, below which TCP begun to decline.

Economic and ecological outcomes of flexible biodiversity offset systems.

PubMed

Habib, Thomas J; Farr, Daniel R; Schneider, Richard R; Boutin, Stan

2013-12-01

The commonly expressed goal of biodiversity offsets is to achieve no net loss of specific biological features affected by development. However, strict equivalency requirements may complicate trading of offset credits, increase costs due to restricted offset placement options, and force offset activities to focus on features that may not represent regional conservation priorities. Using the oil sands industry of Alberta, Canada, as a case study, we evaluated the economic and ecological performance of alternative offset systems targeting either ecologically equivalent areas (vegetation types) or regional conservation priorities (caribou and the Dry Mixedwood natural subregion). Exchanging dissimilar biodiversity elements requires assessment via a generalized metric; we used an empirically derived index of biodiversity intactness to link offsets with losses incurred by development. We considered 2 offset activities: land protection, with costs estimated as the net present value of profits of petroleum and timber resources to be paid as compensation to resource tenure holders, and restoration of anthropogenic footprint, with costs estimated from existing restoration projects. We used the spatial optimization tool MARXAN to develop hypothetical offset networks that met either the equivalent-vegetation or conservation-priority targets. Networks that required offsetting equivalent vegetation cost 2-17 times more than priority-focused networks. This finding calls into question the prudence of equivalency-based systems, particularly in relatively undeveloped jurisdictions, where conservation focuses on limiting and directing future losses. Priority-focused offsets may offer benefits to industry and environmental stakeholders by allowing for lower-cost conservation of valued ecological features and may invite discussion on what land-use trade-offs are acceptable when trading biodiversity via offsets. Resultados Económicos y Ecológicos de Sistemas de Compensación de Biodiversidad Flexible Habib et al. © 2013 Society for Conservation Biology.

Glyphosate-tolerant soybeans remain compositionally equivalent to conventional soybeans (Glycine max L.) during three years of field testing.

PubMed

McCann, Melinda C; Liu, Keshun; Trujillo, William A; Dobert, Raymond C

2005-06-29

Previous studies have shown that the composition of glyphosate-tolerant soybeans (GTS) and selected processed fractions was substantially equivalent to that of conventional soybeans over a wide range of analytes. This study was designed to determine if the composition of GTS remains substantially equivalent to conventional soybeans over the course of several years and when introduced into multiple genetic backgrounds. Soybean seed samples of both GTS and conventional varieties were harvested during 2000, 2001, and 2002 and analyzed for the levels of proximates, lectin, trypsin inhibitor, and isoflavones. The measured analytes are representative of the basic nutritional and biologically active components in soybeans. Results show a similar range of natural variability for the GTS soybeans as well as conventional soybeans. It was concluded that the composition of commercial GTS over the three years of breeding into multiple varieties remains equivalent to that of conventional soybeans.

Probing the Potential of Neutron Imaging for Biomedical and Biological Applications

NASA Astrophysics Data System (ADS)

Watkin, K. L.; Bilheux, H. Z.; Ankner, J. F.

Neutron imaging of biological specimens began soon after the discovery of the neutron by Chadwick in 1932. The first samples included tumors in tissues, internal organs in rats, and bones. These studies mainly employed thermal neutrons and were often compared with X-ray images of the same or equivalent samples. Although neutron scattering is widely used in biological studies, neutron imaging has yet to be exploited to its full capability in this area. This chapter summarizes past and current research efforts to apply neutron radiography to the study of biological specimens, in the expectation that clinical and medical research, as well as forensic science, may benefit from it.

A new formula for normal tissue complication probability (NTCP) as a function of equivalent uniform dose (EUD).

PubMed

Luxton, Gary; Keall, Paul J; King, Christopher R

2008-01-07

To facilitate the use of biological outcome modeling for treatment planning, an exponential function is introduced as a simpler equivalent to the Lyman formula for calculating normal tissue complication probability (NTCP). The single parameter of the exponential function is chosen to reproduce the Lyman calculation to within approximately 0.3%, and thus enable easy conversion of data contained in empirical fits of Lyman parameters for organs at risk (OARs). Organ parameters for the new formula are given in terms of Lyman model m and TD(50), and conversely m and TD(50) are expressed in terms of the parameters of the new equation. The role of the Lyman volume-effect parameter n is unchanged from its role in the Lyman model. For a non-homogeneously irradiated OAR, an equation relates d(ref), n, v(eff) and the Niemierko equivalent uniform dose (EUD), where d(ref) and v(eff) are the reference dose and effective fractional volume of the Kutcher-Burman reduction algorithm (i.e. the LKB model). It follows in the LKB model that uniform EUD irradiation of an OAR results in the same NTCP as the original non-homogeneous distribution. The NTCP equation is therefore represented as a function of EUD. The inverse equation expresses EUD as a function of NTCP and is used to generate a table of EUD versus normal tissue complication probability for the Emami-Burman parameter fits as well as for OAR parameter sets from more recent data.

Total phenolics and total flavonoids in selected Indian medicinal plants.

PubMed

Sulaiman, C T; Balachandran, Indira

2012-05-01

Plant phenolics and flavonoids have a powerful biological activity, which outlines the necessity of their determination. The phenolics and flavonoids content of 20 medicinal plants were determined in the present investigation. The phenolic content was determined by using Folin-Ciocalteu assay. The total flavonoids were measured spectrophotometrically by using the aluminium chloride colorimetric assay. The results showed that the family Mimosaceae is the richest source of phenolics, (Acacia nilotica: 80.63 mg gallic acid equivalents, Acacia catechu 78.12 mg gallic acid equivalents, Albizia lebbeck 66.23 mg gallic acid equivalents). The highest total flavonoid content was revealed in Senna tora which belongs to the family Caesalpiniaceae. The present study also shows the ratio of flavonoids to the phenolics in each sample for their specificity.

Equivalence studies for complex active ingredients and dosage forms.

PubMed

Bhattycharyya, Lokesh; Dabbah, Roger; Hauck, Walter; Sheinin, Eric; Yeoman, Lynn; Williams, Roger

2005-11-17

This article examines the United States Pharmacopeia (USP) and its role in assessing the equivalence and inequivalence of biological and biotechnological drug substances and products-a role USP has played since its founding in 1820. A public monograph in the United States Pharmacopeia-National Formulary helps practitioners and other interested parties understand how an article's strength, quality, and purity should be controlled. Such a monograph is a standard to which all manufactured ingredients and products should conform, and it is a starting point for subsequent-entry manufacturers, recognizing that substantial additional one-time characterization studies may be needed to document equivalence. Review of these studies is the province of the regulatory agency, but compendial tests can provide clarity and guidance in the process.

75 FR 23669 - Application(s) for Duty-Free Entry of Scientific Instruments

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-04

... invite comments on the question of whether instruments of equivalent scientific value, for the purposes... biological interactions at the nano scale. Justification for Duty-Free Entry: There are no instruments of the...

Validation of artificial skin equivalents as in vitro testing systems

NASA Astrophysics Data System (ADS)

Schmitt, Robert; Marx, Ulrich; Walles, Heike; Schober, Lena

2011-03-01

With the increasing complexity of the chemical composition of pharmaceuticals, cosmetics and everyday substances, the awareness of potential health issues and long term damages for humanoid organs is shifting into focus. Artificial in vitro testing systems play an important role in providing reliable test conditions and replacing precarious animal testing. Especially artificial skin equivalents ASEs are used for a broad spectrum of studies like penetration, irritation and corrosion of substances. One major challenge in tissue engineering is the qualification of each individual ASE as in vitro testing system. Due to biological fluctuations, the stratum corneum hornified layer of some ASEs may not fully develop or other defects might occur. For monitoring these effects we developed an fully automated Optical Coherence Tomography device. Here, we present different methods to characterize and evaluate the quality of the ASEs based on image and data processing of OCT B-scans. By analysing the surface structure, defects, like cuts or tears, are detectable. A further indicator for the quality of the ASE is the morphology of the tissue. This allows to determine if the skin model has reached the final growth state. We found, that OCT is a well suited technology for automatically characterizing artificial skin equivalents and validating the application as testing system.

Information Leakage from Logically Equivalent Frames

ERIC Educational Resources Information Center

Sher, Shlomi; McKenzie, Craig R. M.

2006-01-01

Framing effects are said to occur when equivalent frames lead to different choices. However, the equivalence in question has been incompletely conceptualized. In a new normative analysis of framing effects, we complete the conceptualization by introducing the notion of information equivalence. Information equivalence obtains when no…

Radiation dosimetry and biophysical models of space radiation effects

NASA Technical Reports Server (NTRS)

Cucinotta, Francis A.; Wu, Honglu; Shavers, Mark R.; George, Kerry

2003-01-01

Estimating the biological risks from space radiation remains a difficult problem because of the many radiation types including protons, heavy ions, and secondary neutrons, and the absence of epidemiology data for these radiation types. Developing useful biophysical parameters or models that relate energy deposition by space particles to the probabilities of biological outcomes is a complex problem. Physical measurements of space radiation include the absorbed dose, dose equivalent, and linear energy transfer (LET) spectra. In contrast to conventional dosimetric methods, models of radiation track structure provide descriptions of energy deposition events in biomolecules, cells, or tissues, which can be used to develop biophysical models of radiation risks. In this paper, we address the biophysical description of heavy particle tracks in the context of the interpretation of both space radiation dosimetry and radiobiology data, which may provide insights into new approaches to these problems.

Cancer metabolism in space and time: Beyond the Warburg effect.

PubMed

Danhier, Pierre; Bański, Piotr; Payen, Valéry L; Grasso, Debora; Ippolito, Luigi; Sonveaux, Pierre; Porporato, Paolo E

2017-08-01

Altered metabolism in cancer cells is pivotal for tumor growth, most notably by providing energy, reducing equivalents and building blocks while several metabolites exert a signaling function promoting tumor growth and progression. A cancer tissue cannot be simply reduced to a bulk of proliferating cells. Tumors are indeed complex and dynamic structures where single cells can heterogeneously perform various biological activities with different metabolic requirements. Because tumors are composed of different types of cells with metabolic activities affected by different spatial and temporal contexts, it is important to address metabolism taking into account cellular and biological heterogeneity. In this review, we describe this heterogeneity also in metabolic fluxes, thus showing the relative contribution of different metabolic activities to tumor progression according to the cellular context. This article is part of a Special Issue entitled Mitochondria in Cancer, edited by Giuseppe Gasparre, Rodrigue Rossignol and Pierre Sonveaux. Copyright © 2017 Elsevier B.V. All rights reserved.

Method for evaluation of human induced pluripotent stem cell quality using image analysis based on the biological morphology of cells.

PubMed

Wakui, Takashi; Matsumoto, Tsuyoshi; Matsubara, Kenta; Kawasaki, Tomoyuki; Yamaguchi, Hiroshi; Akutsu, Hidenori

2017-10-01

We propose an image analysis method for quality evaluation of human pluripotent stem cells based on biologically interpretable features. It is important to maintain the undifferentiated state of induced pluripotent stem cells (iPSCs) while culturing the cells during propagation. Cell culture experts visually select good quality cells exhibiting the morphological features characteristic of undifferentiated cells. Experts have empirically determined that these features comprise prominent and abundant nucleoli, less intercellular spacing, and fewer differentiating cellular nuclei. We quantified these features based on experts' visual inspection of phase contrast images of iPSCs and found that these features are effective for evaluating iPSC quality. We then developed an iPSC quality evaluation method using an image analysis technique. The method allowed accurate classification, equivalent to visual inspection by experts, of three iPSC cell lines.

Development of Multiple-Frequency Ultrasonic Imaging System Using Multiple Resonance Piezoelectric Transducer

NASA Astrophysics Data System (ADS)

Akiyama, Iwaki; Yoshizumi, Natsuki; Saito, Shigemi; Wada, Yuji; Koyama, Daisuke; Nakamura, Kentaro

2012-07-01

The authors have developed a multiple frequency imaging system using a multiple resonance transducer (MRT) consisting of 1-3 composite materials with a low mechanical quality factor Q bonded together. The MRT has a structure consisting of thin and thick piezoelectric plates, two matching layers, and a backing layer. This makes it possible to obtain B-mode images of satisfactory resolution using ultrasonic pulses owing to their short duration. In this paper, the vibration property of the MRT derived through equivalent-circuit analysis is first shown. By utilizing the result, an MRT capable of transmitting ultrasonic pulses for generation of the images of biological tissues with satisfactory resolution is designed and prototyped. Setting the prototype transducer in the mechanical sector probe of commercial ultrasonic diagnosis equipment, the speckle reduction effect is demonstrated using images of various phantoms to mimic biological tissues and a human thyroid.

An Augmented γ-Spray System to Visualize Biological Effects for Human Body

NASA Astrophysics Data System (ADS)

Manabe, Seiya; Tenzou, Hideki; Kasuga, Takaaki; Iwakura, Yukiko; Johnston, Robert

2017-09-01

The purpose of this study was to develop a new educational system with an easy-to-use interface in order to support comprehension of the biological effects of radiation on the human body within a short period of time. A paint spray-gun was used as a gamma rays source mock-up for the system. The application screen shows the figure of a human body for radiation deposition using the γ-Sprayer, a virtual radiation source, as well as equivalent dosage and a panel for setting the irradiation conditions. While the learner stands in front of the PC monitor, the virtual radiation source is used to deposit radiation on the graphic of the human body that is displayed. Tissue damage is calculated using an interpolation method from the data calculated by the PHITS simulation code in advance while the learner is pulling the trigger with respect to the irradiation time, incident position, and distance from the screen. It was confirmed that the damage was well represented by the interpolation method. The augmented ?-Spray system was assessed by questionnaire. Pre-post questionnaire was taken for our 41 students in National Institute of Technology, Kagawa College. It was also confirmed that the system has a capability of teaching the basic radiation protection concept, quantitative feeling of the radiation dose, and the biological effects

A new method of estimating thermal performance of embryonic development rate yields accurate prediction of embryonic age in wild reptile nests.

PubMed

Rollinson, Njal; Holt, Sarah M; Massey, Melanie D; Holt, Richard C; Nancekivell, E Graham; Brooks, Ronald J

2018-05-01

Temperature has a strong effect on ectotherm development rate. It is therefore possible to construct predictive models of development that rely solely on temperature, which have applications in a range of biological fields. Here, we leverage a reference series of development stages for embryos of the turtle Chelydra serpentina, which was described at a constant temperature of 20 °C. The reference series acts to map each distinct developmental stage onto embryonic age (in days) at 20 °C. By extension, an embryo taken from any given incubation environment, once staged, can be assigned an equivalent age at 20 °C. We call this concept "Equivalent Development", as it maps the development stage of an embryo incubated at a given temperature to its equivalent age at a reference temperature. In the laboratory, we used the concept of Equivalent Development to estimate development rate of embryos of C. serpentina across a series of constant temperatures. Using these estimates of development rate, we created a thermal performance curve measured in units of Equivalent Development (TPC ED ). We then used the TPC ED to predict developmental stage of embryos in several natural turtle nests across six years. We found that 85% of the variation of development stage in natural nests could be explained. Further, we compared the predictive accuracy of the model based on the TPC ED to the predictive accuracy of a degree-day model, where development is assumed to be linearly related to temperature and the amount of accumulated heat is summed over time. Information theory suggested that the model based on the TPC ED better describes variation in developmental stage in wild nests than the degree-day model. We suggest the concept of Equivalent Development has several strengths and can be broadly applied. In particular, studies on temperature-dependent sex determination may be facilitated by the concept of Equivalent Development, as development age maps directly onto the developmental series of the organism, allowing critical periods of sex determination to be delineated without invasive sampling, even under fluctuating temperature. Copyright © 2018 Elsevier Ltd. All rights reserved.

LRP5 regulates human body fat distribution by modulating adipose progenitor biology in a dose- and depot-specific fashion.

PubMed

Loh, Nellie Y; Neville, Matt J; Marinou, Kyriakoula; Hardcastle, Sarah A; Fielding, Barbara A; Duncan, Emma L; McCarthy, Mark I; Tobias, Jonathan H; Gregson, Celia L; Karpe, Fredrik; Christodoulides, Constantinos

2015-02-03

Common variants in WNT pathway genes have been associated with bone mass and fat distribution, the latter predicting diabetes and cardiovascular disease risk. Rare mutations in the WNT co-receptors LRP5 and LRP6 are similarly associated with bone and cardiometabolic disorders. We investigated the role of LRP5 in human adipose tissue. Subjects with gain-of-function LRP5 mutations and high bone mass had enhanced lower-body fat accumulation. Reciprocally, a low bone mineral density-associated common LRP5 allele correlated with increased abdominal adiposity. Ex vivo LRP5 expression was higher in abdominal versus gluteal adipocyte progenitors. Equivalent knockdown of LRP5 in both progenitor types dose-dependently impaired β-catenin signaling and led to distinct biological outcomes: diminished gluteal and enhanced abdominal adipogenesis. These data highlight how depot differences in WNT/β-catenin pathway activity modulate human fat distribution via effects on adipocyte progenitor biology. They also identify LRP5 as a potential pharmacologic target for the treatment of cardiometabolic disorders. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

LRP5 Regulates Human Body Fat Distribution by Modulating Adipose Progenitor Biology in a Dose- and Depot-Specific Fashion

PubMed Central

Loh, Nellie Y.; Neville, Matt J.; Marinou, Kyriakoula; Hardcastle, Sarah A.; Fielding, Barbara A.; Duncan, Emma L.; McCarthy, Mark I.; Tobias, Jonathan H.; Gregson, Celia L.; Karpe, Fredrik; Christodoulides, Constantinos

2015-01-01

Summary Common variants in WNT pathway genes have been associated with bone mass and fat distribution, the latter predicting diabetes and cardiovascular disease risk. Rare mutations in the WNT co-receptors LRP5 and LRP6 are similarly associated with bone and cardiometabolic disorders. We investigated the role of LRP5 in human adipose tissue. Subjects with gain-of-function LRP5 mutations and high bone mass had enhanced lower-body fat accumulation. Reciprocally, a low bone mineral density-associated common LRP5 allele correlated with increased abdominal adiposity. Ex vivo LRP5 expression was higher in abdominal versus gluteal adipocyte progenitors. Equivalent knockdown of LRP5 in both progenitor types dose-dependently impaired β-catenin signaling and led to distinct biological outcomes: diminished gluteal and enhanced abdominal adipogenesis. These data highlight how depot differences in WNT/β-catenin pathway activity modulate human fat distribution via effects on adipocyte progenitor biology. They also identify LRP5 as a potential pharmacologic target for the treatment of cardiometabolic disorders. PMID:25651180

Biological dose estimation for charged-particle therapy using an improved PHITS code coupled with a microdosimetric kinetic model.

PubMed

Sato, Tatsuhiko; Kase, Yuki; Watanabe, Ritsuko; Niita, Koji; Sihver, Lembit

2009-01-01

Microdosimetric quantities such as lineal energy, y, are better indexes for expressing the RBE of HZE particles in comparison to LET. However, the use of microdosimetric quantities in computational dosimetry is severely limited because of the difficulty in calculating their probability densities in macroscopic matter. We therefore improved the particle transport simulation code PHITS, providing it with the capability of estimating the microdosimetric probability densities in a macroscopic framework by incorporating a mathematical function that can instantaneously calculate the probability densities around the trajectory of HZE particles with a precision equivalent to that of a microscopic track-structure simulation. A new method for estimating biological dose, the product of physical dose and RBE, from charged-particle therapy was established using the improved PHITS coupled with a microdosimetric kinetic model. The accuracy of the biological dose estimated by this method was tested by comparing the calculated physical doses and RBE values with the corresponding data measured in a slab phantom irradiated with several kinds of HZE particles. The simulation technique established in this study will help to optimize the treatment planning of charged-particle therapy, thereby maximizing the therapeutic effect on tumors while minimizing unintended harmful effects on surrounding normal tissues.

Method for the prediction of the effective dose equivalent to the crew of the International Space Station

NASA Astrophysics Data System (ADS)

El-Jaby, Samy; Tomi, Leena; Sihver, Lembit; Sato, Tatsuhiko; Richardson, Richard B.; Lewis, Brent J.

2014-03-01

This paper describes a methodology for assessing the pre-mission exposure of space crew aboard the International Space Station (ISS) in terms of an effective dose equivalent. In this approach, the PHITS Monte Carlo code was used to assess the particle transport of galactic cosmic radiation (GCR) and trapped radiation for solar maximum and minimum conditions through an aluminum shield thickness. From these predicted spectra, and using fluence-to-dose conversion factors, a scaling ratio of the effective dose equivalent rate to the ICRU ambient dose equivalent rate at a 10 mm depth was determined. Only contributions from secondary neutrons, protons, and alpha particles were considered in this analysis. Measurements made with a tissue equivalent proportional counter (TEPC) located at Service Module panel 327, as captured through a semi-empirical correlation in the ISSCREM code, where then scaled using this conversion factor for prediction of the effective dose equivalent. This analysis shows that at this location within the service module, the total effective dose equivalent is 10-30% less than the total TEPC dose equivalent. Approximately 75-85% of the effective dose equivalent is derived from the GCR. This methodology provides an opportunity for pre-flight predictions of the effective dose equivalent and therefore offers a means to assess the health risks of radiation exposure on ISS flight crew.

Reformulation of a clinical-dose system for carbon-ion radiotherapy treatment planning at the National Institute of Radiological Sciences, Japan

NASA Astrophysics Data System (ADS)

Inaniwa, Taku; Kanematsu, Nobuyuki; Matsufuji, Naruhiro; Kanai, Tatsuaki; Shirai, Toshiyuki; Noda, Koji; Tsuji, Hiroshi; Kamada, Tadashi; Tsujii, Hirohiko

2015-04-01

At the National Institute of Radiological Sciences (NIRS), more than 8,000 patients have been treated for various tumors with carbon-ion (C-ion) radiotherapy in the past 20 years based on a radiobiologically defined clinical-dose system. Through clinical experience, including extensive dose escalation studies, optimum dose-fractionation protocols have been established for respective tumors, which may be considered as the standards in C-ion radiotherapy. Although the therapeutic appropriateness of the clinical-dose system has been widely demonstrated by clinical results, the system incorporates several oversimplifications such as dose-independent relative biological effectiveness (RBE), empirical nuclear fragmentation model, and use of dose-averaged linear energy transfer to represent the spectrum of particles. We took the opportunity to update the clinical-dose system at the time we started clinical treatment with pencil beam scanning, a new beam delivery method, in 2011. The requirements for the updated system were to correct the oversimplifications made in the original system, while harmonizing with the original system to maintain the established dose-fractionation protocols. In the updated system, the radiation quality of the therapeutic C-ion beam was derived with Monte Carlo simulations, and its biological effectiveness was predicted with a theoretical model. We selected the most used C-ion beam with αr = 0.764 Gy-1 and β = 0.0615 Gy-2 as reference radiation for RBE. The C-equivalent biological dose distribution is designed to allow the prescribed survival of tumor cells of the human salivary gland (HSG) in entire spread-out Bragg peak (SOBP) region, with consideration to the dose dependence of the RBE. This C-equivalent biological dose distribution is scaled to a clinical dose distribution to harmonize with our clinical experiences with C-ion radiotherapy. Treatment plans were made with the original and the updated clinical-dose systems, and both physical and clinical dose distributions were compared with regard to the prescribed dose level, beam energy, and SOBP width. Both systems provided uniform clinical dose distributions within the targets consistent with the prescriptions. The mean physical doses delivered to targets by the updated system agreed with the doses by the original system within ±1.5% for all tested conditions. The updated system reflects the physical and biological characteristics of the therapeutic C-ion beam more accurately than the original system, while at the same time allowing the continued use of the dose-fractionation protocols established with the original system at NIRS.

Total Phenolics and Total Flavonoids in Selected Indian Medicinal Plants

PubMed Central

Sulaiman, C. T.; Balachandran, Indira

2012-01-01

Plant phenolics and flavonoids have a powerful biological activity, which outlines the necessity of their determination. The phenolics and flavonoids content of 20 medicinal plants were determined in the present investigation. The phenolic content was determined by using Folin-Ciocalteu assay. The total flavonoids were measured spectrophotometrically by using the aluminium chloride colorimetric assay. The results showed that the family Mimosaceae is the richest source of phenolics, (Acacia nilotica: 80.63 mg gallic acid equivalents, Acacia catechu 78.12 mg gallic acid equivalents, Albizia lebbeck 66.23 mg gallic acid equivalents). The highest total flavonoid content was revealed in Senna tora which belongs to the family Caesalpiniaceae. The present study also shows the ratio of flavonoids to the phenolics in each sample for their specificity. PMID:23439764

TEPC Response Functions

NASA Technical Reports Server (NTRS)

Shinn, J. L.; Wilson, J. W.

2003-01-01

The tissue equivalent proportional counter had the purpose of providing the energy absorbed from a radiation field and an estimate of the corresponding linear energy transfer (LET) for evaluation of radiation quality to convert to dose equivalent. It was the recognition of the limitations in estimating LET which lead to a new approach to dosimetry, microdosimetry, and the corresponding emphasis on energy deposit in a small tissue volume as the driver of biological response with the defined quantity of lineal energy. In many circumstances, the average of the lineal energy and LET are closely related and has provided a basis for estimating dose equivalent. Still in many cases the lineal is poorly related to LET and brings into question the usefulness as a general purpose device. These relationships are examined in this paper.

N-silyl oxyketene imines are underused yet highly versatile reagents for catalytic asymmetric synthesis

NASA Astrophysics Data System (ADS)

Denmark, Scott E.; Wilson, Tyler W.

2010-11-01

The reactions of acyl anion equivalents (d1 synthons) with carbonyl electrophiles allow for the construction of a wide range of molecules useful for the synthesis of biologically active compounds, natural products and chiral ligands. Despite their utility, significant challenges still exist for developing catalytic, enantioselective variants of these reactions. For example, the asymmetric benzoin process, arguably the most characteristic reaction of d synthetic equivalents, finds no general solution for reactions involving aliphatic acyl anions. In this Article, we introduce a new class of stable, isolable silyl ketene imines derived from protected cyanohydrins. These nucleophiles serve as acyl anion equivalents in Lewis base catalysed aldol addition reactions and allow for the preparation of cross-benzoin and glycolate-aldol products in high yield and with exceptional diastereo- and enantioselectivities.

Enhanced pharmaceutical removal from water in a three step bio-ozone-bio process.

PubMed

de Wilt, Arnoud; van Gijn, Koen; Verhoek, Tom; Vergnes, Amber; Hoek, Mirit; Rijnaarts, Huub; Langenhoff, Alette

2018-07-01

Individual treatment processes like biological treatment or ozonation have their limitations for the removal of pharmaceuticals from secondary clarified effluents with high organic matter concentrations (i.e. 17 mg TOC/L). These limitations can be overcome by combining these two processes for a cost-effective pharmaceutical removal. A three-step biological-ozone-biological (BO 3 B) treatment process was therefore designed for the enhanced pharmaceutical removal from wastewater effluent. The first biological step removed 38% of ozone scavenging TOC, thus proportionally reducing the absolute ozone input for the subsequent ozonation. Complementariness between biological and ozone treatment, i.e. targeting different pharmaceuticals, resulted in cost-effective pharmaceutical removal by the overall BO 3 B process. At a low ozone dose of 0.2 g O 3 /g TOC and an HRT of 1.46 h in the biological reactors, the removal of 8 out of 9 pharmaceuticals exceeded 85%, except for metoprolol (60%). Testing various ozone doses and HRTs revealed that pharmaceuticals were ineffectively removed at 0.1 g O3/g TOC and an HRT of 0.3 h. At HRTs of 0.47 and 1.46 h easily and moderately biodegradable pharmaceuticals such as caffeine, gemfibrozil, ibuprofen, naproxen and sulfamethoxazole were over 95% removed by biological treatment. The biorecalcitrant carbamazepine was completely ozonated at a dose of 0.4 g O 3 /g TOC. Ozonation products are likely biodegraded in the last biological reactor as a 17% TOC removal was found. No appreciable acute toxicity towards D. magna, P. subcapitata and V. fischeri was found after exposure to the influents and effluents of the individual BO 3 B reactors. The BO 3 B process is estimated to increase the yearly wastewater treatment tariff per population equivalent in the Netherlands by less than 10%. Overall, the BO 3 B process is a cost-effective treatment process for the removal of pharmaceuticals from secondary clarified effluents. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Monitoring proton radiation therapy with in-room PET imaging

NASA Astrophysics Data System (ADS)

Zhu, Xuping; España, Samuel; Daartz, Juliane; Liebsch, Norbert; Ouyang, Jinsong; Paganetti, Harald; Bortfeld, Thomas R.; El Fakhri, Georges

2011-07-01

We used a mobile positron emission tomography (PET) scanner positioned within the proton therapy treatment room to study the feasibility of proton range verification with an in-room, stand-alone PET system, and compared with off-line equivalent studies. Two subjects with adenoid cystic carcinoma were enrolled into a pilot study in which in-room PET scans were acquired in list-mode after a routine fractionated treatment session. The list-mode PET data were reconstructed with different time schemes to generate in-room short, in-room long and off-line equivalent (by skipping coincidences from the first 15 min during the list-mode reconstruction) PET images for comparison in activity distribution patterns. A phantom study was followed to evaluate the accuracy of range verification for different reconstruction time schemes quantitatively. The in-room PET has a higher sensitivity compared to the off-line modality so that the PET acquisition time can be greatly reduced from 30 to <5 min. Features in deep-site, soft-tissue regions were better retained with in-room short PET acquisitions because of the collection of 15O component and lower biological washout. For soft tissue-equivalent material, the distal fall-off edge of an in-room short acquisition is deeper compared to an off-line equivalent scan, indicating a better coverage of the high-dose end of the beam. In-room PET is a promising low cost, high sensitivity modality for the in vivo verification of proton therapy. Better accuracy in Monte Carlo predictions, especially for biological decay modeling, is necessary.

Continuous form-dependent focusing of non-spherical microparticles in a highly diluted suspension with the help of microfluidic spirals

NASA Astrophysics Data System (ADS)

Roth, Tanja; Sprenger, Lisa; Odenbach, Stefan; Häfeli, Urs O.

2018-04-01

Microfluidic spirals are able to focus non-spherical microparticles in diluted suspension due to the Dean effect. A secondary flow establishes in a curved channel, consisting of two counter-rotating vortices, which transport particles to an equilibrium position near the inner wall of the channel. The relevant size parameter, which is responsible for successful focusing, is the ratio between the particle diameter of a sphere and the hydraulic diameter, which is a characteristic of the microfluidic spiral. A non-spherical particle has not one but several different size parameters. This study investigated the minor and major axes, the equivalent spherical diameter, and the maximal rotational diameter as an equivalent to the spherical diameter. Using a polydimethylsiloxane (PDMS)-based microfluidic device with spirals, experiments were conducted with artificial peanut-shaped and ellipsoidal particles sized between 3 and 9 μm as well as with the bacteria Bacillus subtilis. Our investigations show that the equivalent spherical diameter, the major axis, and the maximal rotational diameter of a non-spherical particle can predict successful focusing. The minor axis is not suitable for this purpose. Non-spherical particles focused when the ratio of their equivalent spherical diameter to the hydraulic diameter of the channel was larger than 0.07. The particles also focused when the ratio between the maximal rotational diameter or the major axis and the hydraulic diameter was larger than 0.01. These results may help us to separate non-spherical biological particles, such as circulating tumor cells or pathogenic bacteria, from blood in future experimental studies.

Factors affecting healing after arthroscopic rotator cuff repair

PubMed Central

Abtahi, Amir M; Granger, Erin K; Tashjian, Robert Z

2015-01-01

Rotator cuff repair has been shown to have good long-term results. Unfortunately, a significant proportion of repairs still fail to heal. Many factors, both patient and surgeon related, can influence healing after repair. Older age, larger tear size, worse muscle quality, greater muscle-tendon unit retraction, smoking, osteoporosis, diabetes and hypercholesterolemia have all shown to negatively influence tendon healing. Surgeon related factors that can influence healing include repair construct-single vs double row, rehabilitation, and biologics including platelet rich plasma and mesenchymal stem cells. Double-row repairs are biomechanically stronger and have better healing rates compared with single-row repairs although clinical outcomes are equivalent between both constructs. Slower, less aggressive rehabilitation programs have demonstrated improved healing with no negative effect on final range of motion and are therefore recommended after repair of most full thickness tears. Additionally no definitive evidence supports the use of platelet rich plasma or mesenchymal stem cells regarding improvement of healing rates and clinical outcomes. Further research is needed to identify effective biologically directed augmentations that will improve healing rates and clinical outcomes after rotator cuff repair. PMID:25793161

Arsenite binding-induced zinc loss from PARP-1 is equivalent to zinc deficiency in reducing PARP-1 activity, leading to inhibition of DNA repair

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sun, Xi; Zhou, Xixi; Du, Libo

2014-01-15

Inhibition of DNA repair is a recognized mechanism for arsenic enhancement of ultraviolet radiation-induced DNA damage and carcinogenesis. Poly(ADP-ribose) polymerase-1 (PARP-1), a zinc finger DNA repair protein, has been identified as a sensitive molecular target for arsenic. The zinc finger domains of PARP-1 protein function as a critical structure in DNA recognition and binding. Since cellular poly(ADP-ribosyl)ation capacity has been positively correlated with zinc status in cells, we hypothesize that arsenite binding-induced zinc loss from PARP-1 is equivalent to zinc deficiency in reducing PARP-1 activity, leading to inhibition of DNA repair. To test this hypothesis, we compared the effects ofmore » arsenite exposure with zinc deficiency, created by using the membrane-permeable zinc chelator TPEN, on 8-OHdG formation, PARP-1 activity and zinc binding to PARP-1 in HaCat cells. Our results show that arsenite exposure and zinc deficiency had similar effects on PARP-1 protein, whereas supplemental zinc reversed these effects. To investigate the molecular mechanism of zinc loss induced by arsenite, ICP-AES, near UV spectroscopy, fluorescence, and circular dichroism spectroscopy were utilized to examine arsenite binding and occupation of a peptide representing the first zinc finger of PARP-1. We found that arsenite binding as well as zinc loss altered the conformation of zinc finger structure which functionally leads to PARP-1 inhibition. These findings suggest that arsenite binding to PARP-1 protein created similar adverse biological effects as zinc deficiency, which establishes the molecular mechanism for zinc supplementation as a potentially effective treatment to reverse the detrimental outcomes of arsenic exposure. - Highlights: • Arsenite binding is equivalent to zinc deficiency in reducing PARP-1 function. • Zinc reverses arsenic inhibition of PARP-1 activity and enhancement of DNA damage. • Arsenite binding and zinc loss alter the conformation of zinc finger structure.« less

Characterization of a Human Skin Equivalent Model to Study the Effects of Ultraviolet B Radiation on Keratinocytes

PubMed Central

Van Lonkhuyzen, Derek R.; Dawson, Rebecca A.; Kimlin, Michael G.; Upton, Zee

2014-01-01

The incidences of skin cancers resulting from chronic ultraviolet radiation (UVR) exposure are on the incline in both Australia and globally. Hence, the cellular and molecular pathways that are associated with UVR-induced photocarcinogenesis need to be urgently elucidated, in order to develop more robust preventative and treatment strategies against skin cancers. In vitro investigations into the effects of UVR (in particular, the highly mutagenic UVB wavelength) have, to date, mainly involved the use of cell culture and animal models. However, these models possess biological disparities to native skin, which, to some extent, have limited their relevance to the in vivo situation. To address this, we characterized a three-dimensional, tissue-engineered human skin equivalent (HSE) model (consisting of primary human keratinocytes cultured on a dermal-derived scaffold) as a representation of a more physiologically relevant platform to study keratinocyte responses to UVB. Significantly, we demonstrate that this model retains several important epidermal properties of native skin. Moreover, UVB irradiation of the HSE constructs was shown to induce key markers of photodamage in the HSE keratinocytes, including the formation of cyclobutane pyrimidine dimers, the activation of apoptotic pathways, the accumulation of p53, and the secretion of inflammatory cytokines. Importantly, we also demonstrate that the UVB-exposed HSE constructs retain the capacity for epidermal repair and regeneration after photodamage. Together, our results demonstrate the potential of this skin equivalent model as a tool to study various aspects of the acute responses of human keratinocytes to UVB radiation damage. PMID:24219750

Case studies of hydrogen sulphide occupational exposure incidents in the UK.

PubMed

Jones, Kate

2014-12-15

The UK Health and Safety Executive has investigated several incidents of workplace accidents involving hydrogen sulphide exposure in recent years. Biological monitoring has been used in some incidents to determine the cause of unconsciousness resulting from these incidents and as a supporting evidence in regulatory enforcement. This paper reports on three case incidents and discusses the use of biological monitoring in such cases. Biological monitoring has a role in identifying hydrogen sulphide exposure in incidents, whether these are occupational or in the wider environment. Sample type, time of collection and sample storage are important factors in the applicability of this technique. For non-fatal incidents, multiple urine samples are recommended at two or more time points between the incident and 15 h post-exposure. For routine occupational monitoring, post-shift samples should be adequate. Due to endogenous levels of urinary thiosulphate, it is likely that exposures in excess of 12 ppm for 30 min (or 360 ppm/min equivalent) would be detectable using biological monitoring. This is within the Acute Exposure Guideline Level 2 (the level of the chemical in air at or above which there may be irreversible or other serious long-lasting effects or impaired ability to escape) for hydrogen sulphide. Crown Copyright © 2014. Published by Elsevier Ireland Ltd. All rights reserved.

DETERMINATION OF INDUCED RADIOACTIVITY IN THE SECOND COSMIC SPACESHIP

DOE Office of Scientific and Technical Information (OSTI.GOV)

Matveev, V.V.; Sokolov, A.D.

1961-01-01

The residual gamma activity in a biological specimen on board the second Soviet cosmic spaceship was determined. The biological specimens were in the form of cylinders (3.8-cm dia., 4-cm long) with a total weight of 86 g. The activity of the specimens was measured after return to earth, and it was found that if there was a residual gamma activity 15 days after the return to earth it did not exceed 10-/sup 10/ g equivalents of Ra. (OTS)

Space Radiation Organ Doses for Astronauts on Past and Future Missions

NASA Technical Reports Server (NTRS)

Cucinotta, Francis A.

2007-01-01

We review methods and data used for determining astronaut organ dose equivalents on past space missions including Apollo, Skylab, Space Shuttle, NASA-Mir, and International Space Station (ISS). Expectations for future lunar missions are also described. Physical measurements of space radiation include the absorbed dose, dose equivalent, and linear energy transfer (LET) spectra, or a related quantity, the lineal energy (y) spectra that is measured by a tissue equivalent proportional counter (TEPC). These data are used in conjunction with space radiation transport models to project organ specific doses used in cancer and other risk projection models. Biodosimetry data from Mir, STS, and ISS missions provide an alternative estimate of organ dose equivalents based on chromosome aberrations. The physical environments inside spacecraft are currently well understood with errors in organ dose projections estimated as less than plus or minus 15%, however understanding the biological risks from space radiation remains a difficult problem because of the many radiation types including protons, heavy ions, and secondary neutrons for which there are no human data to estimate risks. The accuracy of projections of organ dose equivalents described here must be supplemented with research on the health risks of space exposure to properly assess crew safety for exploration missions.

Design and simulation of optoelectronic complementary dual neural elements for realizing a family of normalized vector 'equivalence-nonequivalence' operations

NASA Astrophysics Data System (ADS)

Krasilenko, Vladimir G.; Nikolsky, Aleksandr I.; Lazarev, Alexander A.; Magas, Taras E.

2010-04-01

Equivalence models (EM) advantages of neural networks (NN) are shown in paper. EMs are based on vectormatrix procedures with basic operations of continuous neurologic: normalized vector operations "equivalence", "nonequivalence", "autoequivalence", "autononequivalence". The capacity of NN on the basis of EM and of its modifications, including auto-and heteroassociative memories for 2D images, exceeds in several times quantity of neurons. Such neuroparadigms are very perspective for processing, recognition, storing large size and strongly correlated images. A family of "normalized equivalence-nonequivalence" neuro-fuzzy logic operations on the based of generalized operations fuzzy-negation, t-norm and s-norm is elaborated. A biologically motivated concept and time pulse encoding principles of continuous logic photocurrent reflexions and sample-storage devices with pulse-width photoconverters have allowed us to design generalized structures for realization of the family of normalized linear vector operations "equivalence"-"nonequivalence". Simulation results show, that processing time in such circuits does not exceed units of micro seconds. Circuits are simple, have low supply voltage (1-3 V), low power consumption (milliwatts), low levels of input signals (microwatts), integrated construction, satisfy the problem of interconnections and cascading.

A first vascularized skin equivalent as an alternative to animal experimentation.

PubMed

Groeber, Florian; Engelhardt, Lisa; Lange, Julia; Kurdyn, Szymon; Schmid, Freia F; Rücker, Christoph; Mielke, Stephan; Walles, Heike; Hansmann, Jan

2016-01-01

Tissue-engineered skin equivalents mimic key aspects of the human skin, and can thus be employed as wound coverage for large skin defects or as in vitro test systems as an alternative to animal models. However, current skin equivalents lack a functional vasculature limiting clinical and research applications. This study demonstrates the generation of a vascularized skin equivalent with a perfused vascular network by combining a biological vascularized scaffold (BioVaSc) based on a decellularized segment of a porcine jejunum and a tailored bioreactor system. Briefly, the BioVaSc was seeded with human fibroblasts, keratinocytes, and human microvascular endothelial cells. After 14 days at the air-liquid interface, hematoxylin & eosin and immunohistological staining revealed a specific histological architecture representative of the human dermis and epidermis including a papillary-like architecture at the dermal-epidermal-junction. The formation of the skin barrier was measured non-destructively using impedance spectroscopy. Additionally, endothelial cells lined the walls of the formed vessels that could be perfused with a physiological volume flow. Due to the presence of a complex in-vivo-like vasculature, the here shown skin equivalent has the potential for skin grafting and represents a sophisticated in vitro model for dermatological research.

SU-F-T-124: Radiation Biological Equivalent Presentations OfLEM-1 and MKM Approaches in the Carbon-Ion Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hsi, W; Jiang, G; Sheng, Y

Purpose: To study the correlations of the radiation biological equivalent doses (BED) along depth and lateral distance between LEM-1 and MKM approaches. Methods: In NIRS-MKM (Microdosimetric Kinetic Model) approach, the prescribed BED, referred as C-Eq, doses aims to present the relative biological effectiveness (RBE) for different energies of carbon-ions on a fixed 10% survival value of HCG cell with respect to convention X-ray. Instead of a fixed 10% survival, the BED doses of LEM-1 (Local Effect Model) approach, referred as X-Eq, aims to present the RBE over the whole survival curve of chordoma-like cell with alpha/beta ratio of 2.0. Themore » relationship of physical doses as a function of C-Eq and X-Eq doses were investigated along depth and lateral distance for various sizes of cubic targets in water irradiated by carbon-ions. Results: At the center of each cubic target, the trends between physical and C-Eq or X-Eq doses can be described by a linear and 2nd order polynomial functions, respectively. Using fit functions can then calculate a scaling factor between C-Eq and X-Eq doses to have similar physical doses. With equalized C-Eq and X-Eq doses at the depth of target center, over- and under-estimated X-Eq to C-Eq are seen for depths before and after the target center, respectively. Near the distal edge along depth, sharp rising of RBE value is observed for X-Eq, but sharp dropping of RBE value is observed for C-Eq. For lateral locations near and just outside 50% dose level, sharp raising of RBE value is also seen for X-Eq, while only minor increasing with fast dropping for C-Eq. Conclusion: An analytical function to model the differences between the CEq and X-Eq doses along depth and lateral distance need to further investigated to explain varied clinic outcome of specific cancers using two different approaches to calculated BED doses.« less

Moving toward focal therapy in prostate cancer: dual-isotope permanent seed implants as a possible solution.

PubMed

Todor, Dorin A; Barani, Igor J; Lin, Peck-Sun; Anscher, Mitchell S

2011-09-01

To compare the ability of single- and dual-isotope prostate seed implants to escalate biologically effective dose (BED) to foci of disease while reducing prescription dose to the prostate. Nine plans, using 125I, 103Pd, and 131Cs alone and in combination were created retrospectively for 2 patients. Ultrasound and MRI/MRS datasets were used for treatment planning. Voxel-by-voxel BED was calculated for single- and dual-isotope plans. Equivalent uniform BED (EUBED) was used to compare plans. The MRS-positive planning target volumes (PTVi) were delineated along with PTV (prostate+5 mm), rectum, and urethra. Single-isotope implants, prescribed to conventional doses, were generated to achieve good PTV coverage. The PTVi were prospectively used to generate implants using mixtures of isotopes. For mixed-radioisotope implants, we also explored the impact on EUBED of lowering prescription doses by 15%. The EUBED of PTVi in the setting of primary 125I implant increased 20-66% when 103Pd and 131Cs were used compared with 125I boost. Decreasing prescription dose by 15% in mixed-isotope implants results in a potential 10% reduction in urethral EUBED with preservation of PTV coverage while still boosting PTVi (up to 80%). When radiobiologic parameters corresponding to more-aggressive disease are assigned to foci, faster-decaying isotopes used in mixed implants have the potential to preserve the equivalent biological effect of mono-isotope implants considering less-aggressive disease distributed in the entire prostate. This is a hypothesis-generating study proposing a treatment paradigm that could be the middle ground between whole-gland irradiation and focal-only treatment. The use of two isotopes concurrent with decreasing the minimal peripheral dose is shown to increase EUBED of selected subvolumes while preserving the therapeutic effect at the level of the gland. Copyright © 2011 Elsevier Inc. All rights reserved.

Moving Toward Focal Therapy in Prostate Cancer: Dual-Isotope Permanent Seed Implants as a Possible Solution

DOE Office of Scientific and Technical Information (OSTI.GOV)

Todor, Dorin A., E-mail: dtodor@mcvh-vcu.edu; Barani, Igor J.; Lin, Peck-Sun

2011-09-01

Purpose: To compare the ability of single- and dual-isotope prostate seed implants to escalate biologically effective dose (BED) to foci of disease while reducing prescription dose to the prostate. Methods and Materials: Nine plans, using {sup 125}I, {sup 103}Pd, and {sup 131}Cs alone and in combination were created retrospectively for 2 patients. Ultrasound and MRI/MRS datasets were used for treatment planning. Voxel-by-voxel BED was calculated for single- and dual-isotope plans. Equivalent uniform BED (EUBED) was used to compare plans. The MRS-positive planning target volumes (PTV{sub i}) were delineated along with PTV (prostate + 5 mm), rectum, and urethra. Single-isotope implants,more » prescribed to conventional doses, were generated to achieve good PTV coverage. The PTV{sub i} were prospectively used to generate implants using mixtures of isotopes. For mixed-radioisotope implants, we also explored the impact on EUBED of lowering prescription doses by 15%. Results: The EUBED of PTV{sub i} in the setting of primary {sup 125}I implant increased 20-66% when {sup 103}Pd and {sup 131}Cs were used compared with {sup 125}I boost. Decreasing prescription dose by 15% in mixed-isotope implants results in a potential 10% reduction in urethral EUBED with preservation of PTV coverage while still boosting PTV{sub i} (up to 80%). When radiobiologic parameters corresponding to more-aggressive disease are assigned to foci, faster-decaying isotopes used in mixed implants have the potential to preserve the equivalent biological effect of mono-isotope implants considering less-aggressive disease distributed in the entire prostate. Conclusions: This is a hypothesis-generating study proposing a treatment paradigm that could be the middle ground between whole-gland irradiation and focal-only treatment. The use of two isotopes concurrent with decreasing the minimal peripheral dose is shown to increase EUBED of selected subvolumes while preserving the therapeutic effect at the level of the gland.« less

Biological Effects of High-Energy Neutrons Measured In Vivo Using a Vertebrate Model

PubMed Central

Kuhne, Wendy W.; Gersey, Brad B.; Wilkins, Richard; Wu, Honglu; Wender, Stephen A.; George, Varghese; Dynan, William S.

2009-01-01

Interaction of solar protons and galactic cosmic radiation with the atmosphere and other materials produces high-energy secondary neutrons from below 1 to 1000 MeV and higher. Although secondary neutrons may provide an appreciable component of the radiation dose equivalent received by space and high-altitude air travelers, the biological effects remain poorly defined, particularly in vivo in intact organisms. Here we describe the acute response of Japanese medaka (Oryzias latipes) embryos to a beam of high-energy spallation neutrons that mimics the energy spectrum of secondary neutrons encountered aboard spacecraft and high-altitude aircraft. To determine RBE, embryos were exposed to 0–0.5 Gy of high-energy neutron radiation or 0–15 Gy of reference γ radiation. The radiation response was measured by imaging apoptotic cells in situ in defined volumes of the embryo, an assay that provides a quantifiable, linear dose response. The slope of the dose response in the developing head, relative to reference γ radiation, indicates an RBE of 24.9 (95% CI 13.6–40.7). A higher RBE of 48.1 (95% CI 30.0–66.4) was obtained based on overall survival. A separate analysis of apoptosis in muscle showed an overall nonlinear response, with the greatest effects at doses of less than 0.3 Gy. Results of this experiment indicate that medaka are a useful model for investigating biological damage associated with high-energy neutron exposure. PMID:19772468

Systematic measurement of lineal energy distributions for proton, He and Si ion beams over a wide energy range using a wall-less tissue equivalent proportional counter.

PubMed

Tsuda, Shuichi; Sato, Tatsuhiko; Takahashi, Fumiaki; Satoh, Daiki; Sasaki, Shinichi; Namito, Yoshihito; Iwase, Hiroshi; Ban, Shuichi; Takada, Masashi

2012-01-01

The frequency distributions of the lineal energy, y, of 160 MeV proton, 150 MeV/u helium, and 490 MeV/u silicon ion beams were measured using a wall-less tissue equivalent proportional counter (TEPC) with a site size of 0.72 µm. The measured frequency distributions of y as well as the dose-mean values, y(D), agree with the corresponding data calculated using the microdosimetric function of the particle and heavy ion transport code system PHITS. The values of y(D) increase in the range of LET below ~10 keV µm(-1) because of discrete energy deposition by delta rays, while the relation is reversed above ~10 keV µm(-1) as the amount of energy escaping via delta rays increases. These results indicate that care should be taken with the difference between y(D) and LET when estimating the ionization density that usually relates to relative biological effectiveness (RBE) of energetic heavy ions.

The Mg2+-containing Water Cluster of Mammalian Cytochrome c Oxidase Collects Four Pumping Proton Equivalents in Each Catalytic Cycle.

PubMed

Yano, Naomine; Muramoto, Kazumasa; Shimada, Atsuhiro; Takemura, Shuhei; Baba, Junpei; Fujisawa, Hidenori; Mochizuki, Masao; Shinzawa-Itoh, Kyoko; Yamashita, Eiki; Tsukihara, Tomitake; Yoshikawa, Shinya

2016-11-11

Bovine heart cytochrome c oxidase (CcO) pumps four proton equivalents per catalytic cycle through the H-pathway, a proton-conducting pathway, which includes a hydrogen bond network and a water channel operating in tandem. Protons are transferred by H 3 O + through the water channel from the N-side into the hydrogen bond network, where they are pumped to the P-side by electrostatic repulsion between protons and net positive charges created at heme a as a result of electron donation to O 2 bound to heme a 3 To block backward proton movement, the water channel remains closed after O 2 binding until the sequential four-proton pumping process is complete. Thus, the hydrogen bond network must collect four proton equivalents before O 2 binding. However, a region with the capacity to accept four proton equivalents was not discernable in the x-ray structures of the hydrogen bond network. The present x-ray structures of oxidized/reduced bovine CcO are improved from 1.8/1.9 to 1.5/1.6 Å resolution, increasing the structural information by 1.7/1.6 times and revealing that a large water cluster, which includes a Mg 2+ ion, is linked to the H-pathway. The cluster contains enough proton acceptor groups to retain four proton equivalents. The redox-coupled x-ray structural changes in Glu 198 , which bridges the Mg 2+ and Cu A (the initial electron acceptor from cytochrome c) sites, suggest that the Cu A -Glu 198 -Mg 2+ system drives redox-coupled transfer of protons pooled in the water cluster to the H-pathway. Thus, these x-ray structures indicate that the Mg 2+ -containing water cluster is the crucial structural element providing the effective proton pumping in bovine CcO. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Student-generated illustrations and written narratives of biological science concepts: The effect on community college life science students' achievement in and attitudes toward science

NASA Astrophysics Data System (ADS)

Harvey, Robert Christopher

The purpose of this study was to determine the effects of two conceptually based instructional strategies on science achievement and attitudes of community college biological science students. The sample consisted of 277 students enrolled in General Biology 1, Microbiology, and Human Anatomy and Physiology 1. Control students were comprised of intact classes from the 2005 Spring semester; treatment students from the 2005 Fall semester were randomly assigned to one of two groups within each course: written narrative (WN) and illustration (IL). WN students prepared in-class written narratives related to cell theory and metabolism, which were taught in all three courses. IL students prepared in-class illustrations of the same concepts. Control students received traditional lecture/lab during the entire class period and neither wrote in-class descriptions nor prepared in-class illustrations of the targeted concepts. All groups were equivalent on age, gender, ethnicity, GPA, and number of college credits earned and were blinded to the study. All interventions occurred in class and no group received more attention or time to complete assignments. A multivariate analysis of covariance (MANCOVA) via multiple regression was the primary statistical strategy used to test the study's hypotheses. The model was valid and statistically significant. Independent follow-up univariate analyses relative to each dependent measure found that no research factor had a significant effect on attitude, but that course-teacher, group membership, and student academic characteristics had a significant effect (p < .05) on achievement: (1) Biology students scored significantly lower in achievement than A&P students; (2) Microbiology students scored significantly higher in achievement than Biology students; (3) Written Narrative students scored significantly higher in achievement than Control students; and (4) GPA had a significant effect on achievement. In addition, given p < .08: (1) Microbiology students averaged lower in achievement than A&P students; (2) Illustration students averaged higher in achievement than Control students; and (3) Written Narrative students averaged higher in achievement than Illustration students. Findings suggest that science achievement can be enhanced via student-generated illustrations and written narratives, these interventions had no effect on attitudes toward science, and the interventions benefited A&P students more than Microbiology and Biology students.

A fast and efficient python library for interfacing with the Biological Magnetic Resonance Data Bank.

PubMed

Smelter, Andrey; Astra, Morgan; Moseley, Hunter N B

2017-03-17

The Biological Magnetic Resonance Data Bank (BMRB) is a public repository of Nuclear Magnetic Resonance (NMR) spectroscopic data of biological macromolecules. It is an important resource for many researchers using NMR to study structural, biophysical, and biochemical properties of biological macromolecules. It is primarily maintained and accessed in a flat file ASCII format known as NMR-STAR. While the format is human readable, the size of most BMRB entries makes computer readability and explicit representation a practical requirement for almost any rigorous systematic analysis. To aid in the use of this public resource, we have developed a package called nmrstarlib in the popular open-source programming language Python. The nmrstarlib's implementation is very efficient, both in design and execution. The library has facilities for reading and writing both NMR-STAR version 2.1 and 3.1 formatted files, parsing them into usable Python dictionary- and list-based data structures, making access and manipulation of the experimental data very natural within Python programs (i.e. "saveframe" and "loop" records represented as individual Python dictionary data structures). Another major advantage of this design is that data stored in original NMR-STAR can be easily converted into its equivalent JavaScript Object Notation (JSON) format, a lightweight data interchange format, facilitating data access and manipulation using Python and any other programming language that implements a JSON parser/generator (i.e., all popular programming languages). We have also developed tools to visualize assigned chemical shift values and to convert between NMR-STAR and JSONized NMR-STAR formatted files. Full API Reference Documentation, User Guide and Tutorial with code examples are also available. We have tested this new library on all current BMRB entries: 100% of all entries are parsed without any errors for both NMR-STAR version 2.1 and version 3.1 formatted files. We also compared our software to three currently available Python libraries for parsing NMR-STAR formatted files: PyStarLib, NMRPyStar, and PyNMRSTAR. The nmrstarlib package is a simple, fast, and efficient library for accessing data from the BMRB. The library provides an intuitive dictionary-based interface with which Python programs can read, edit, and write NMR-STAR formatted files and their equivalent JSONized NMR-STAR files. The nmrstarlib package can be used as a library for accessing and manipulating data stored in NMR-STAR files and as a command-line tool to convert from NMR-STAR file format into its equivalent JSON file format and vice versa, and to visualize chemical shift values. Furthermore, the nmrstarlib implementation provides a guide for effectively JSONizing other older scientific formats, improving the FAIRness of data in these formats.

Assessing the Ecological Risk of Polycyclic Aromatic Hydrocarbons in Sediments at Langkawi Island, Malaysia

PubMed Central

Nasher, Essam; Heng, Lee Yook; Zakaria, Zuriati; Surif, Salmijah

2013-01-01

Tourism-related activities such as the heavy use of boats for transportation are a significant source of petroleum hydrocarbons that may harm the ecosystem of Langkawi Island. The contamination and toxicity levels of polycyclic aromatic hydrocarbon (PAH) in the sediments of Langkawi were evaluated using sediment quality guidelines (SQGs) and toxic equivalent factors. Ten samples were collected from jetties and fish farms around the island in December 2010. A gas chromatography/flame ionization detector (GC/FID) was used to analyse the 18 PAHs. The concentration of total PAHs was found to range from 869 ± 00 to 1637 ± 20 ng g−1 with a mean concentration of 1167.00 ± 24 ng g−1, lower than the SQG effects range-low (3442 ng g−1). The results indicated that PAHs may not cause acute biological damage. Diagnostic ratios and principal component analysis suggested that the PAHs were likely to originate from pyrogenic and petrogenic sources. The toxic equivalent concentrations of the PAHs ranged from 76.3 to 177 ng TEQ/g d.w., which is lower compared to similar studies. The results of mean effects range-median quotient of the PAHs were lower than 0.1, which indicate an 11% probability of toxicity effect. Hence, the sampling sites were determined to be the low-priority sites. PMID:24163633

Assessing the ecological risk of polycyclic aromatic hydrocarbons in sediments at Langkawi Island, Malaysia.

PubMed

Nasher, Essam; Heng, Lee Yook; Zakaria, Zuriati; Surif, Salmijah

2013-01-01

Tourism-related activities such as the heavy use of boats for transportation are a significant source of petroleum hydrocarbons that may harm the ecosystem of Langkawi Island. The contamination and toxicity levels of polycyclic aromatic hydrocarbon (PAH) in the sediments of Langkawi were evaluated using sediment quality guidelines (SQGs) and toxic equivalent factors. Ten samples were collected from jetties and fish farms around the island in December 2010. A gas chromatography/flame ionization detector (GC/FID) was used to analyse the 18 PAHs. The concentration of total PAHs was found to range from 869 ± 00 to 1637 ± 20 ng g⁻¹ with a mean concentration of 1167.00 ± 24 ng g⁻¹, lower than the SQG effects range-low (3442 ng g⁻¹). The results indicated that PAHs may not cause acute biological damage. Diagnostic ratios and principal component analysis suggested that the PAHs were likely to originate from pyrogenic and petrogenic sources. The toxic equivalent concentrations of the PAHs ranged from 76.3 to 177 ng TEQ/g d.w., which is lower compared to similar studies. The results of mean effects range-median quotient of the PAHs were lower than 0.1, which indicate an 11% probability of toxicity effect. Hence, the sampling sites were determined to be the low-priority sites.

Isobio software: biological dose distribution and biological dose volume histogram from physical dose conversion using linear-quadratic-linear model.

PubMed

Jaikuna, Tanwiwat; Khadsiri, Phatchareewan; Chawapun, Nisa; Saekho, Suwit; Tharavichitkul, Ekkasit

2017-02-01

To develop an in-house software program that is able to calculate and generate the biological dose distribution and biological dose volume histogram by physical dose conversion using the linear-quadratic-linear (LQL) model. The Isobio software was developed using MATLAB version 2014b to calculate and generate the biological dose distribution and biological dose volume histograms. The physical dose from each voxel in treatment planning was extracted through Computational Environment for Radiotherapy Research (CERR), and the accuracy was verified by the differentiation between the dose volume histogram from CERR and the treatment planning system. An equivalent dose in 2 Gy fraction (EQD 2 ) was calculated using biological effective dose (BED) based on the LQL model. The software calculation and the manual calculation were compared for EQD 2 verification with pair t -test statistical analysis using IBM SPSS Statistics version 22 (64-bit). Two and three-dimensional biological dose distribution and biological dose volume histogram were displayed correctly by the Isobio software. Different physical doses were found between CERR and treatment planning system (TPS) in Oncentra, with 3.33% in high-risk clinical target volume (HR-CTV) determined by D 90% , 0.56% in the bladder, 1.74% in the rectum when determined by D 2cc , and less than 1% in Pinnacle. The difference in the EQD 2 between the software calculation and the manual calculation was not significantly different with 0.00% at p -values 0.820, 0.095, and 0.593 for external beam radiation therapy (EBRT) and 0.240, 0.320, and 0.849 for brachytherapy (BT) in HR-CTV, bladder, and rectum, respectively. The Isobio software is a feasible tool to generate the biological dose distribution and biological dose volume histogram for treatment plan evaluation in both EBRT and BT.

Beyond effective teaching: Enhancing students’ metacognitive skill through guided inquiry

NASA Astrophysics Data System (ADS)

Adnan; Bahri, Arsad

2018-01-01

This research was quasi experimental with pretest posttes non-equivalent control group design. This research aimed to compare metacognitive skill of students between tought by guided inquiry and traditional teaching. Sample of this research was the students at even semester at the first year, Department of Biology, Faculty of Mathematics and Natural Sciences, Universitas Negeri Makassar, Indonesia. The data of students’ metacognitive skill was measured by essay test. The data was analyzed by inferential statistic of ANCOVA test. The result of research showed that there was the effect of teaching model towards metacognitive skill of students. Students were tought by guided inquiry had higher metacognitive skill than tought by traditional teaching. The lecturer can use the guided inquiry model in others courses with considering the course materials and also student characteristics.

Kinetic Tetrazolium Microtiter Assay

NASA Technical Reports Server (NTRS)

Pierson, Duane L.; Stowe, Raymond; Koenig, David

1993-01-01

Kinetic tetrazolium microtiter assay (KTMA) involves use of tetrazolium salts and Triton X-100 (or equivalent), nontoxic, in vitro color developer solubilizing colored metabolite formazan without injuring or killing metabolizing cells. Provides for continuous measurement of metabolism and makes possible to determine rate of action of antimicrobial agent in real time as well as determines effective inhibitory concentrations. Used to monitor growth after addition of stimulatory compounds. Provides for kinetic determination of efficacy of biocide, greatly increasing reliability and precision of results. Also used to determine relative effectiveness of antimicrobial agent as function of time. Capability of generating results on day of test extremely important in treatment of water and waste, disinfection of hospital rooms, and in pharmaceutical, agricultural, and food-processing industries. Assay also used in many aspects of cell biology.

Measurement and simulation of lineal energy distribution at the CERN high energy facility with a tissue equivalent proportional counter.

PubMed

Rollet, S; Autischer, M; Beck, P; Latocha, M

2007-01-01

The response of a tissue equivalent proportional counter (TEPC) in a mixed radiation field with a neutron energy distribution similar to the radiation field at commercial flight altitudes has been studied. The measurements have been done at the CERN-EU High-Energy Reference Field (CERF) facility where a well-characterised radiation field is available for intercomparison. The TEPC instrument used by the ARC Seibersdorf Research is filled with pure propane gas at low pressure and can be used to determine the lineal energy distribution of the energy deposition in a mass of gas equivalent to a 2 microm diameter volume of unit density tissue, of similar size to the nuclei of biological cells. The linearity of the detector response was checked both in term of dose and dose rate. The effect of dead-time has been corrected. The influence of the detector exposure location and orientation in the radiation field on the dose distribution was also studied as a function of the total dose. The microdosimetric distribution of the absorbed dose as a function of the lineal energy has been obtained and compared with the same distribution simulated with the FLUKA Monte Carlo transport code. The dose equivalent was calculated by folding this distribution with the quality factor as a function of linear energy transfer. The comparison between the measured and simulated distributions show that they are in good agreement. As a result of this study the detector is well characterised, thanks also to the numerical simulations the instrument response is well understood, and it's currently being used onboard the aircrafts to evaluate the dose to aircraft crew caused by cosmic radiation.

Phage Display of a Biologically Active Bacillus thuringiensis Toxin

PubMed Central

Kasman, Laura M.; Lukowiak, Andrew A.; Garczynski, Stephen F.; McNall, Rebecca J.; Youngman, Phil; Adang, Michael J.

1998-01-01

Activated forms of Bacillus thuringiensis insecticidal toxins have consistently been found to form insoluble and inactive precipitates when they are expressed in Escherichia coli. Genetic engineering of these proteins to improve their effectiveness as biological pesticides would be greatly facilitated by the ability to express them in E. coli, since the molecular biology tools available for Bacillus are limited. To this end, we show that activated B. thuringiensis toxin (Cry1Ac) can be expressed in E. coli as a translational fusion with the minor phage coat protein of filamentous phage. Phage particles displaying this fusion protein were viable, infectious, and as lethal as pure toxin on a molar basis when the phage particles were fed to insects susceptible to native Cry1Ac. Enzyme-linked immunosorbent assay and Western blot analysis showed the fusion protein to be antigenically equivalent to native toxin, and micropanning with anti-Cry1Ac antibody was positive for the toxin-expressing phage. Phage display of B. thuringiensis toxins has many advantages over previous expression systems for these proteins and should make it possible to construct large libraries of toxin variants for screening or biopanning. PMID:9687463

A novel avalanche-confinement TEPC for microdosimetry at nanometric level

NASA Astrophysics Data System (ADS)

Bortot, D.; Agosteo, S.; Colautti, P.; Conte, V.; Introini, M. V.; Lorenzoli, M.; Pasquato, S.; Pola, A.

2017-09-01

The tissue equivalent proportional counter (TEPC) is the most accurate device for measuring the microdosimetric properties of a particle beam, showing to properly assess the relative biological effectiveness by linking the physical parameters of the radiation with the corresponding biological response. Nevertheless no detailed information on the track structure of the impinging particles can be obtained, since the lower operation limit of the common TEPCs is about 0.3 ?m. On the other hand, the pattern of particle interactions at the nanometer level, which demonstrated to have a strong correlation with radiation-induced damages to the DNA, is directly measured by only three different nanodosimeters worldwide: practical instruments are not yet available. The gap between microdosimetry and track-nanodosimetry can be filled partially by extending the TEPC response down to the nanometric region. A feasibility study of a novel TEPC designed to simulate biological sites in the nanometric domain was performed. The present paper aims at describing the design, the development and the characterization of this avalanche-confinement TEPC. Irradiations with photons, fast neutrons and low-energy carbon ions demonstrated the capability of this TEPC of measuring in the range 0.3 μm - 25 nm.

The activation of fibroblast growth factors by heparin: synthesis, structure, and biological activity of heparin-like oligosaccharides.

PubMed

de Paz, J L; Angulo, J; Lassaletta, J M; Nieto, P M; Redondo-Horcajo, M; Lozano, R M; Giménez-Gallego, G; Martín-Lomas, M

2001-09-03

An effective strategy has been designed for the synthesis of oligosaccharides of different sizes structurally related to the regular region of heparin; this is illustrated by the preparation of hexasaccharide 1 and octasaccharide 2. This synthetic strategy provides the oligosaccharide sequence containing a D-glucosamine unit at the nonreducing end that is not available either by enzymatic or chemical degradation of heparin. It may permit, after slight modifications, the preparation of oligosaccharide fragments with different charge distribution as well. NMR spectroscopy and molecular dynamics simulations have shown that the overall structure of 1 in solution is a stable right-hand helix with four residues per turn. Hexasaccharide 1 and, most likely, octasaccharide 2 are, therefore, chemically well-defined structural models of naturally occurring heparin-like oligosaccharides for use in binding and biological activity studies. Both compounds 1 and 2 induce the mitogenic activity of acid fibroblast growth factor (FGF1), with the half-maximum activating concentration of 2 being equivalent to that of heparin. Sedimentation equilibrium analysis with compound 2 suggests that heparin-induced FGF1 dimerization is not an absolute requirement for biological activity.

Animated Cell Biology: A Quick and Easy Method for Making Effective, High-Quality Teaching Animations

PubMed Central

2006-01-01

There is accumulating evidence that animations aid learning of dynamic concepts in cell biology. However, existing animation packages are expensive and difficult to learn, and the subsequent production of even short animations can take weeks to months. Here I outline the principles and sequence of steps for producing high-quality PowerPoint animations in less than a day that are suitable for teaching in high school through college/university. After developing the animation it can be easily converted to any appropriate movie file format using Camtasia Studio for Internet or classroom presentations. Thus anyone who can use PowerPoint has the potential to make animations. Students who viewed the approximately 3-min PowerPoint/Camtasia Studio animation “Calcium and the Dual Signalling Pathway” over 15 min scored significantly higher marks on a subsequent quiz than those who had viewed still graphics with text for an equivalent time. In addition, results from student evaluations provided some data validating the use of such animations in cell biology teaching with some interesting caveats. Information is also provided on how such animations can be modified or updated easily or shared with others who can modify them to fit their own needs. PMID:17012217

Predicting in vivo effect levels for repeat-dose systemic toxicity using chemical, biological, kinetic and study covariates.

PubMed

Truong, Lisa; Ouedraogo, Gladys; Pham, LyLy; Clouzeau, Jacques; Loisel-Joubert, Sophie; Blanchet, Delphine; Noçairi, Hicham; Setzer, Woodrow; Judson, Richard; Grulke, Chris; Mansouri, Kamel; Martin, Matthew

2018-02-01

In an effort to address a major challenge in chemical safety assessment, alternative approaches for characterizing systemic effect levels, a predictive model was developed. Systemic effect levels were curated from ToxRefDB, HESS-DB and COSMOS-DB from numerous study types totaling 4379 in vivo studies for 1247 chemicals. Observed systemic effects in mammalian models are a complex function of chemical dynamics, kinetics, and inter- and intra-individual variability. To address this complex problem, systemic effect levels were modeled at the study-level by leveraging study covariates (e.g., study type, strain, administration route) in addition to multiple descriptor sets, including chemical (ToxPrint, PaDEL, and Physchem), biological (ToxCast), and kinetic descriptors. Using random forest modeling with cross-validation and external validation procedures, study-level covariates alone accounted for approximately 15% of the variance reducing the root mean squared error (RMSE) from 0.96 log 10 to 0.85 log 10  mg/kg/day, providing a baseline performance metric (lower expectation of model performance). A consensus model developed using a combination of study-level covariates, chemical, biological, and kinetic descriptors explained a total of 43% of the variance with an RMSE of 0.69 log 10  mg/kg/day. A benchmark model (upper expectation of model performance) was also developed with an RMSE of 0.5 log 10  mg/kg/day by incorporating study-level covariates and the mean effect level per chemical. To achieve a representative chemical-level prediction, the minimum study-level predicted and observed effect level per chemical were compared reducing the RMSE from 1.0 to 0.73 log 10  mg/kg/day, equivalent to 87% of predictions falling within an order-of-magnitude of the observed value. Although biological descriptors did not improve model performance, the final model was enriched for biological descriptors that indicated xenobiotic metabolism gene expression, oxidative stress, and cytotoxicity, demonstrating the importance of accounting for kinetics and non-specific bioactivity in predicting systemic effect levels. Herein, we generated an externally predictive model of systemic effect levels for use as a safety assessment tool and have generated forward predictions for over 30,000 chemicals.

Rényi entropy, abundance distribution, and the equivalence of ensembles.

PubMed

Mora, Thierry; Walczak, Aleksandra M

2016-05-01

Distributions of abundances or frequencies play an important role in many fields of science, from biology to sociology, as does the Rényi entropy, which measures the diversity of a statistical ensemble. We derive a mathematical relation between the abundance distribution and the Rényi entropy, by analogy with the equivalence of ensembles in thermodynamics. The abundance distribution is mapped onto the density of states, and the Rényi entropy to the free energy. The two quantities are related in the thermodynamic limit by a Legendre transform, by virtue of the equivalence between the micro-canonical and canonical ensembles. In this limit, we show how the Rényi entropy can be constructed geometrically from rank-frequency plots. This mapping predicts that non-concave regions of the rank-frequency curve should result in kinks in the Rényi entropy as a function of its order. We illustrate our results on simple examples, and emphasize the limitations of the equivalence of ensembles when a thermodynamic limit is not well defined. Our results help choose reliable diversity measures based on the experimental accuracy of the abundance distributions in particular frequency ranges.

Antineurodegenerative effect of phenolic extracts and caffeic acid derivatives in romaine lettuce on neuron-like PC-12 cells.

PubMed

Im, Sung-Eun; Yoon, Hyungeun; Nam, Tae-Gyu; Heo, Ho Jin; Lee, Chang Yong; Kim, Dae-Ok

2010-08-01

In recent decades, romaine lettuce has been one of the fastest growing vegetables with respect to its consumption and production. An understanding is needed of the effect of major phenolic phytochemicals from romaine lettuce on biological protection for neuron-like PC-12 cells. Phenolics in fresh romaine lettuce were extracted, and then its total phenolics and total antioxidant capacity were measured spectrophotometrically. Neuroprotective effects of phenolic extract of romaine lettuce and its pure caffeic acid derivatives (caffeic, chicoric, chlorogenic, and isochlorogenic acids) in PC-12 cells were evaluated using two different in vitro methods: lactate dehydrogenase release and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reduction assays. Total phenolics and total antioxidant capacity of 100 g of fresh romaine lettuce averaged 22.7 mg of gallic acid equivalents and 31.0 mg of vitamin C equivalents, respectively. The phenolic extract of romaine lettuce protected PC-12 cells against oxidative stress caused by H(2)O(2) in a dose-dependent manner. Isochlorogenic acid, one of the phenolics in romaine lettuce, showed stronger neuroprotection than the other three caffeic acid derivatives also found in the lettuce. Although romaine lettuce had lower levels of phenolics and antioxidant capacity compared to other common vegetables, its contribution to total antioxidant capacity and antineurodegenerative effect in human diets would be higher because of higher amounts of its daily per capita consumption compared to other common vegetables.

40 CFR 721.1765 - 2-Substituted benzotriazole.

Code of Federal Regulations, 2010 CFR

2010-07-01

... (l) and (q). (iv) Release to water. Requirements as specified in § 721.90 (a)(4), (b)(4), (c)(4), -(where N = 80 ). However, contrary to § 721.91(a)(4), if the waste stream containing the PMN substance will be treated using biological treatment (activated sludge or equivalent) plus clarification, then...

TOXIC EQUIVALENCY APPROACH FOR DIOXINS: AN EXAMPLE OF DOSE ADDITIVITY

EPA Science Inventory

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD; dioxin) is often called the most toxic man-made compound. However, it is but the prototype for a family of structurally related compounds which have a common mechanism of action, induce a common spectrum of biological responses, and are...

Glucose-Induced Acidification in Yeast Cultures

ERIC Educational Resources Information Center

Myers, Alan; Bourn, Julia; Pool, Brynne

2005-01-01

We present an investigation (for A-level biology students and equivalent) into the mechanism of glucose-induced extracellular acidification in unbuffered yeast suspensions. The investigation is designed to enhance understanding of aspects of the A-level curriculum that relate to the phenomenon (notably glucose catabolism) and to develop key skills…

43 CFR 11.73 - Quantification phase-resource recoverability analysis.

Code of Federal Regulations, 2010 CFR

2010-10-01

... equivalent resources efforts are undertaken beyond response actions performed or anticipated shall be estimated. This time period shall be used as the “No Action-Natural Recovery” period for purposes of § 11.82... requirements of biological species involved, including their reaction or tolerance to the oil or hazardous...

Sample Size for Biosimilar Trials: In Defense of Synthesis.

PubMed

Clark, Timothy; Jo, Sook Jung; Phillips, Alan

2018-05-01

Biosimilars are biological products similar to, but not the same as, the innovator products. Both the European Medicines Agency and the Food and Drug Administration have released detailed guidance on the development of biosimilars. This guidance requires the pivotal phase 3 clinical study to have an equivalence design, which means that the study objective is to demonstrate that one treatment is neither "worse than" nor "better than" the other by some "clinically unimportant" amount. The most critical and controversial step in designing such a study is the choice of equivalence margin, as this determines the conclusion of the study. In this paper, we outline the methodology for determining an equivalence margin and, through case studies on biosimilar trastuzumab (HERCEPTIN ) and biosimilar bevacizumab (AVASTIN), explain the challenges of applying this in practice and why the synthesis method should be given greater consideration by regulatory authorities and biosimilar developers.

Response of capacitive micromachined ultrasonic transducers

NASA Astrophysics Data System (ADS)

Ge, Lifeng

2008-10-01

Capacitive micromachined ultrasonic transducers (CMUTs) have been developed for airborne ultrasonic applications, acoustic imaging, and chemical and biological detections. Much attention is also paid how to optimize their performance, so that the accurate simulation of the transmitting response of the CMUTs becomes extremely significant. This paper focuses on determining the total input mechanical impedance accountings for damping, and its resistance part is obtained by the calculated natural frequency and equivalent lumped parameters, and the typical 3-dB bandwidth. Thus, the transmitting response can be calculated by using the input mechanical impedance. Moreover, the equivalent electrical circuit can be also established by the determined lumped parameters.

Route and Type of Formulation Administered Influences the Absorption and Disposition of Vitamin B12 Levels in Serum

PubMed Central

Zhou, Joyce; Manuel, Rachel; Dal Forno, Serena; Rutolo, David

2018-01-01

The administration of biological compounds that optimize health benefits is an ever-evolving therapeutic goal. Pharmaceutical and other adjunctive biological compounds have been administered via many different routes in order to produce a systemic pharmacological effect. The article summarizes the findings from an Australian comparative study in adults administered vitamin B12 through different oral delivery platforms. A total of 16 subjects (9 males, 7 females) voluntarily partook in a comparative clinical study of five different vitamin B12 formulations across a six-month period, completing 474 person-hours of cumulative contribution, that was equivalent to an n = 60 participation. A nanoparticle delivered vitamin B12 through a NanoCelle platform was observed to be significantly (p < 0.05) better absorbed than all other dose equivalent platforms (i.e., tablets, emulsions, or liposomes) from baseline to 1, 3, and 6 h of the study period. The nanoparticle platform delivered vitamin B12 demonstrated an enhanced and significant absorption profile as exemplified by rapid systemic detection (i.e., 1 h from baseline) when administered to the oro-buccal mucosa with no reports of any adverse events of toxicity. The nanoparticle formulation of methylcobalamin (1000 µg/dose in 0.3 mL volume) showed bioequivalence only with a chewable-dissolvable tablet that administered a five times higher dose of methylcobalamin (5000 µg) per tablet. This study has demonstrated that an active metabolite embedded in a functional biomaterial (NanoCelle) may constitute a drug delivery method that can better access the circulatory system. PMID:29361736

An optimization based study of equivalent circuit models for representing recordings at the neuron-electrode interface

PubMed Central

Thakore, Vaibhav; Molnar, Peter; Hickman, James J.

2014-01-01

Extracellular neuroelectronic interfacing is an emerging field with important applications in the fields of neural prosthetics, biological computation and biosensors. Traditionally, neuron-electrode interfaces have been modeled as linear point or area contact equivalent circuits but it is now being increasingly realized that such models cannot explain the shapes and magnitudes of the observed extracellular signals. Here, results were compared and contrasted from an unprecedented optimization based study of the point contact models for an extracellular ‘on-cell’ neuron-patch electrode and a planar neuron-microelectrode interface. Concurrent electrophysiological recordings from a single neuron simultaneously interfaced to three distinct electrodes (intracellular, ‘on-cell’ patch and planar microelectrode) allowed novel insights into the mechanism of signal transduction at the neuron-electrode interface. After a systematic isolation of the nonlinear neuronal contribution to the extracellular signal, a consistent underestimation of the simulated supra-threshold extracellular signals compared to the experimentally recorded signals was observed. This conclusively demonstrated that the dynamics of the interfacial medium contribute nonlinearly to the process of signal transduction at the neuron-electrode interface. Further, an examination of the optimized model parameters for the experimental extracellular recordings from sub- and supra-threshold stimulations of the neuron-electrode junctions revealed that ionic transport at the ‘on-cell’ neuron-patch electrode is dominated by diffusion whereas at the neuron-microelectrode interface the electric double layer (EDL) effects dominate. Based on this study, the limitations of the equivalent circuit models in their failure to account for the nonlinear EDL and ionic electrodiffusion effects occurring during signal transduction at the neuron-electrode interfaces are discussed. PMID:22695342

Phenolic profile and antioxidant activity from peels and seeds of melon (Cucumis melo L. var. reticulatus) and their antiproliferative effect in cancer cells.

PubMed

Rolim, P M; Fidelis, G P; Padilha, C E A; Santos, E S; Rocha, H A O; Macedo, G R

2018-03-01

Melon (Cucumis melo L.) has high economic value and in recent years, its production has increased; however, part of the fruit is wasted. Usually, inedible parts such as peel and seeds are discarded during processing and consumption. Extracts of melon residues were prepared and their phenolic compounds, antioxidants and antiproliferative activities were evaluated. Total phenolic compounds were found in hydroethanolic, hydromethanolic, and aqueous extracts, especially for melon peel (1.016 mg gallic acid equivalent/100 g). Flavonoids total content found for melon peel aqueous extract was 262 µg of catechin equivalent (CA)/100 g. In all extracts of melon peel significant amounts of gallic acid, catechin, and eugenol were found. For total antioxidant capacity, reported as ascorbic acid equivalent, the hydroethanolic and hydromethanolic extracts in peels and hydromethanolic in seeds were 89, 74, and 83 mg/g, respectively. Different extracts of melon showed iron and copper ions chelating activity at different concentrations, especially melon peel aqueous extract, reaching values of 61% for iron and 84% for copper. The hydroethanolic extract of melon peel presented a significant ability for hydroxyl radicals scavenging (68%). To assess the antiproliferative potential in human cancer cell lines, such as kidney carcinoma, colorectal carcinoma, cervical adenocarcinoma and cervical carcinoma, MTT assay was performed. The proliferation was inhibited by 20-85% at extracts concentrations of 0.1-1.0 mg/mL in all cancer cell lines. The results suggest that melon residues extracts display a high antioxidant activity in in vitro assays and have effective biological activity against the growth of human tumor cells.

Phenolic profile and antioxidant activity from peels and seeds of melon (Cucumis melo L. var. reticulatus) and their antiproliferative effect in cancer cells

PubMed Central

Rolim, P.M.; Fidelis, G.P.; Padilha, C.E.A.; Santos, E.S.; Rocha, H.A.O.; Macedo, G.R.

2018-01-01

Melon (Cucumis melo L.) has high economic value and in recent years, its production has increased; however, part of the fruit is wasted. Usually, inedible parts such as peel and seeds are discarded during processing and consumption. Extracts of melon residues were prepared and their phenolic compounds, antioxidants and antiproliferative activities were evaluated. Total phenolic compounds were found in hydroethanolic, hydromethanolic, and aqueous extracts, especially for melon peel (1.016 mg gallic acid equivalent/100 g). Flavonoids total content found for melon peel aqueous extract was 262 µg of catechin equivalent (CA)/100 g. In all extracts of melon peel significant amounts of gallic acid, catechin, and eugenol were found. For total antioxidant capacity, reported as ascorbic acid equivalent, the hydroethanolic and hydromethanolic extracts in peels and hydromethanolic in seeds were 89, 74, and 83 mg/g, respectively. Different extracts of melon showed iron and copper ions chelating activity at different concentrations, especially melon peel aqueous extract, reaching values of 61% for iron and 84% for copper. The hydroethanolic extract of melon peel presented a significant ability for hydroxyl radicals scavenging (68%). To assess the antiproliferative potential in human cancer cell lines, such as kidney carcinoma, colorectal carcinoma, cervical adenocarcinoma and cervical carcinoma, MTT assay was performed. The proliferation was inhibited by 20–85% at extracts concentrations of 0.1–1.0 mg/mL in all cancer cell lines. The results suggest that melon residues extracts display a high antioxidant activity in in vitro assays and have effective biological activity against the growth of human tumor cells. PMID:29513789

New Proof-of-Concept in Viral Inactivation: Virucidal Efficacy of 405 nm Light Against Feline Calicivirus as a Model for Norovirus Decontamination.

PubMed

Tomb, Rachael M; Maclean, Michelle; Coia, John E; Graham, Elizabeth; McDonald, Michael; Atreya, Chintamani D; MacGregor, Scott J; Anderson, John G

2017-06-01

The requirement for novel decontamination technologies for use in hospitals is ever present. One such system uses 405 nm visible light to inactivate microorganisms via ROS-generated oxidative damage. Although effective for bacterial and fungal inactivation, little is known about the virucidal effects of 405 nm light. Norovirus (NoV) gastroenteritis outbreaks often occur in the clinical setting, and this study was designed to investigate potential inactivation effects of 405 nm light on the NoV surrogate, feline calicivirus (FCV). FCV was exposed to 405 nm light whilst suspended in minimal and organically-rich media to establish the virucidal efficacy and the effect biologically-relevant material may play in viral susceptibility. Antiviral activity was successfully demonstrated with a 4 Log 10 (99.99%) reduction in infectivity when suspended in minimal media evident after a dose of 2.8 kJ cm -2 . FCV exposed in artificial faeces, artificial saliva, blood plasma and other organically rich media exhibited an equivalent level of inactivation using between 50-85% less dose of the light, indicating enhanced inactivation when the virus is present in organically-rich biologically-relevant media. Further research in this area could aid in the development of 405 nm light technology for effective NoV decontamination within the hospital environment.

Systematic Review with Network Meta-Analysis: Comparative Efficacy of Biologics in the Treatment of Moderately to Severely Active Ulcerative Colitis.

PubMed

Vickers, Adrian D; Ainsworth, Claire; Mody, Reema; Bergman, Annika; Ling, Caroline S; Medjedovic, Jasmina; Smyth, Michael

2016-01-01

Biological therapies are increasingly used to treat ulcerative colitis (UC). To compare the efficacy of biologics in adults with moderately-to-severely active UC, stratified by prior exposure to anti-tumour necrosis factor (anti-TNF) therapy. A systematic literature review was undertaken to identify studies of biologics approved for UC. Network meta-analysis was conducted for endpoints at induction and maintenance. Seven studies were included in the meta-analysis of induction treatment for anti-TNF therapy-naïve patients. All biologics were more effective than placebo in inducing clinical response, clinical remission, and mucosal healing. Infliximab demonstrated a statistically significant improvement over adalimumab in clinical response (odds ratio [OR] [95% credible interval (CrI)]: 2.19 [1.35-3.55]), clinical remission (OR [95% CrI]: 2.81 [1.49-5.49]), and mucosal healing (OR [95% CrI]: 2.23 [1.21-4.14]); there were no other significant differences between biologics for induction efficacy. Five studies were included in the meta-analysis of maintenance treatment, two studies rerandomised responder patients at end of induction, and three followed the same patients 'straight through'. To account for design differences, the number of responders at end of induction was assumed to be equivalent to the number rerandomised. Vedolizumab showed significantly different durable clinical response from comparators (OR [95% CrI] infliximab 3.18 [1.14-9.20], golimumab 2.33 [1.04-5.41], and adalimumab 3.96 [1.67-9.84]). In anti-TNF therapy-experienced patients, only vedolizumab and adalimumab could be compared. At induction, no significant differences in efficacy were seen. During maintenance, vedolizumab showed significantly improved rates of mucosal healing versus adalimumab (OR [95% CrI]: 6.72 [1.36-41.0]). This study expands the understanding of comparative efficacies of biologic treatments for UC, encompassing outcomes and populations not previously studied. All biologic treatments were effective for UC during induction. Vedolizumab demonstrated possible clinical benefits in the maintenance setting versus all comparators, irrespective of prior anti-TNF exposure and after adjusting for differences in study design.

Peptide-Like Molecules (PLMs): A Journey from Peptide Bond Isosteres to Gramicidin S Mimetics and Mitochondrial Targeting Agents

PubMed Central

Wipf, Peter; Xiao, Jingbo; Stephenson, Corey R. J.

2010-01-01

Peptides are natural ligands and substrates for receptors and enzymes and exhibit broad physiological effects. However, their use as therapeutic agents often suffers from poor bioavailability and insufficient membrane permeability. The success of peptide mimicry hinges on the ability of bioisosteres, in particular peptide bond replacements, to adopt suitable secondary structures relevant to peptide strands and position functional groups in equivalent space. This perspective highlights past and ongoing studies in our group that involve new methods development as well as specific synthetic library preparations and applications in chemical biology, with the goal to enhance the use of alkene and cyclopropane peptide bond isosteres. PMID:20725595

Biologic interventions for fatigue in rheumatoid arthritis.

PubMed

Almeida, Celia; Choy, Ernest H S; Hewlett, Sarah; Kirwan, John R; Cramp, Fiona; Chalder, Trudie; Pollock, Jon; Christensen, Robin

2016-06-06

Fatigue is a common and potentially distressing symptom for patients with rheumatoid arthritis (RA), with no accepted evidence-based management guidelines. Evidence suggests that biologic interventions improve symptoms and signs in RA as well as reducing joint damage. To evaluate the effect of biologic interventions on fatigue in rheumatoid arthritis. We searched the following electronic databases up to 1 April 2014: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Current Controlled Trials Register, the National Research Register Archive, The UKCRN Portfolio Database, AMED, CINAHL, PsycINFO, Social Science Citation Index, Web of Science, and Dissertation Abstracts International. In addition, we checked the reference lists of articles identified for inclusion for additional studies and contacted key authors. We included randomised controlled trials if they evaluated a biologic intervention in people with rheumatoid arthritis and had self reported fatigue as an outcome measure. Two reviewers selected relevant trials, assessed methodological quality and extracted data. Where appropriate, we pooled data in meta-analyses using a random-effects model. We identified 32 studies for inclusion in this current review. Twenty studies evaluated five anti-tumour necrosis factor (anti-TNF) biologic agents (adalimumab, certolizumab, etanercept, golimumab and infliximab), and 12 studies focused on five non-anti-TNF biologic agents (abatacept, canakinumab, rituximab, tocilizumab and an anti-interferon gamma monoclonal antibody). All but two of the studies were double-blind randomised placebo-controlled trials. In some trials, patients could receive concomitant disease-modifying anti-rheumatic drugs (DMARDs). These studies added either biologics or placebo to DMARDs. Investigators did not change the dose of the latter from baseline. In total, these studies included 9946 participants in the intervention groups and 4682 participants in the control groups. Overall, quality of randomised controlled trials was moderate with a low to unclear risk of bias in the reporting of the outcome of fatigue. We downgraded the quality of the studies from high to moderate because of potential reporting bias (studies included post hoc analyses favouring reporting of positive result and did not always include all randomised individuals). Some studies recruited only participants with early disease. The studies used five different instruments to assess fatigue in these studies: the Functional Assessment of Chronic Illness Therapy Fatigue Domain (FACIT-F), Short Form-36 Vitality Domain (SF-36 VT), Visual Analogue Scale (VAS) (0 to 100 or 0 to 10) and the Numerical Rating Scale (NRS). We calculated standard mean differences for pooled data in meta-analyses. Overall treatment by biologic agents led to statistically significant reduction in fatigue with a standardised mean difference of -0.43 (95% confidence interval (CI) -0.38 to -0.49). This equates to a difference of 6.45 units (95% CI 5.7 to 7.35) of FACIT-F score (range 0 to 52). Both types of biologic agents achieved a similar level of improvement: for anti-TNF agents, this stood at -0.42 (95% CI -0.35 to -0.49), equivalent to 6.3 units (95% CI 5.3 to 7.4) on the FACIT-F score; and for non-anti-TNF agents, it was -0.46 (95% CI -0.39 to -0.53), equivalent to 6.9 units (95% CI 5.85 to 7.95) on the FACIT-F score. In most studies, the double-blind period was 24 weeks or less. No study assessed long-term changes in fatigue. Treatment with biologic interventions in patients with active RA can lead to a small to moderate improvement in fatigue. The magnitude of improvement is similar for anti-TNF and non-anti-TNF biologics. However, it is unclear whether the improvement results from a direct action of the biologics on fatigue or indirectly through reduction in inflammation, disease activity or some other mechanism.

Thermal cooking changes the profile of phenolic compounds, but does not attenuate the anti-inflammatory activities of black rice.

PubMed

Bhawamai, Sassy; Lin, Shyh-Hsiang; Hou, Yuan-Yu; Chen, Yue-Hwa

2016-01-01

Evidence on biological activities of cooked black rice is limited. This study examined the effects of washing and cooking on the bioactive ingredients and biological activities of black rice. Cooked rice was prepared by washing 0-3 times followed by cooking in a rice cooker. The acidic methanol extracts of raw and cooked rice were used for the analyses. Raw black rice, both washed and unwashed, had higher contents of polyphenols, anthocyanins, and cyanidin-3-glucoside (C3G), but lower protocatechuic acid (PA), than did cooked samples. Similarly, raw rice extracts were higher in ferric-reducing antioxidant power (FRAP) activities than extracts of cooked samples. Nonetheless, extracts of raw and cooked rice showed similar inhibitory potencies on nitric oxide, tumor necrosis factor-α, and interleukin-6 productions in lipopolysaccharide-activated macrophages, whereas equivalent amounts of C3G and PA did not possess such inhibitory effects. Thermal cooking decreased total anthocyanin and C3G contents and the FRAP antioxidative capacity, but did not affect anti-inflammatory activities of black rice. Neither C3G nor PA contributed to the anti-inflammatory activity of black rice.

Screening and advanced lipid phenotyping in familial hypercholesterolemia: The Very Large Database of Lipids Study-17 (VLDL-17).

PubMed

Miller, P Elliott; Martin, Seth S; Toth, Peter P; Santos, Raul D; Blaha, Michael J; Nasir, Khurram; Virani, Salim S; Post, Wendy S; Blumenthal, Roger S; Jones, Steven R

2015-01-01

Familial hypercholesterolemia (FH) is an autosomal dominant dyslipidemia characterized by defective low-density lipoprotein (LDL) clearance. The aim of this study was to compare Friedewald-estimated LDL cholesterol (LDL-C) to biologic LDL-C in individuals screening positive for FH and then further characterize FH phenotypes. We studied 1,320,581 individuals from the Very Large Database of Lipids, referred from 2009 to 2011 for Vertical Auto Profile ultracentrifugation testing. Friedewald LDL-C was defined as the cholesterol content of LDL-C, intermediate-density lipoprotein cholesterol, and lipoprotein(a) cholesterol (Lp(a)-C), with LDL-C representing biologic LDL-C. Using Friedewald LDL-C, we phenotypically categorized patients by the National Lipid Association guideline age-based screening thresholds for FH. In those meeting criteria, we categorized patients using population percentile-equivalent biologic LDL-C cutpoints and explored Lp(a)-C and remnant lipoprotein cholesterol (RLP-C) levels. Overall, 3829 patients met phenotypic criteria for FH by Friedewald LDL-C screening (FH+). Of those screening FH+, 78.8% were above and 21.2% were below the population percentile-equivalent biologic LDL-C. The mean difference in Friedewald biologic LDL-C percentiles was -0.01 (standard deviation, 0.17) for those above, and 1.92 (standard deviation, 9.16) for those below, respectively. Over 1 of 3 were found to have an elevated Lp(a)-C and over 50% had RLP-C greater than 95th percentile of the entire VLDL population. Of those who screened FH+, Friedewald and biologic LDL-C levels were closely correlated. Large proportions of the FH+ group had excess levels of Lp(a)-C and RLP-C. Future studies are warranted to study these mixed phenotypic groups and determine the role for further risk stratification and treatment algorithms. Copyright © 2015 National Lipid Association. Published by Elsevier Inc. All rights reserved.

The effect of cooperative learning on the attitudes toward science and the achievement of students in a non-science majors' general biology laboratory course at an urban community college

NASA Astrophysics Data System (ADS)

Chung-Schickler, Genevieve C.

The purpose of this study was to evaluate the effect of cooperative learning strategies on students' attitudes toward science and achievement in BSC 1005L, a non-science majors' general biology laboratory course at an urban community college. Data were gathered on the participants' attitudes toward science and cognitive biology level pre and post treatment in BSC 1005L. Elements of the Learning Together model developed by Johnson and Johnson and the Student Team-Achievement Divisions model created by Slavin were incorporated into the experimental sections of BSC 1005L. Four sections of BSC 1005L participated in this study. Participants were enrolled in the 1998 spring (January) term. Students met weekly in a two hour laboratory session. The treatment was administered to the experimental group over a ten week period. A quasi-experimental pretest-posttest control group design was used. Students in the cooperative learning group (nsb1 = 27) were administered the Test of Science-Related Attitudes (TOSRA) and the cognitive biology test at the same time as the control group (nsb2 = 19) (at the beginning and end of the term). Statistical analyses confirmed that both groups were equivalent regarding ethnicity, gender, college grade point average and number of absences. Independent sample t-tests performed on pretest mean scores indicated no significant differences in the TOSRA scale two or biology knowledge between the cooperative learning group and the control group. The scores of TOSRA scales: one, three, four, five, six, and seven were significantly lower in the cooperative learning group. Independent sample t-tests of the mean score differences did not show any significant differences in posttest attitudes toward science or biology knowledge between the two groups. Paired t-tests did not indicate any significant differences on the TOSRA or biology knowledge within the cooperative learning group. Paired t-tests did show significant differences within the control group on TOSRA scale two and biology knowledge. ANCOVAs did not indicate any significant differences on the post mean scores of the TOSRA or biology knowledge adjusted by differences in the pretest mean scores. Analysis of the research data did not show any significant correlation between attitudes toward science and biology knowledge.

Relative source allocation of TDI to drinking water for derivation of a criterion for chloroform: a Monte-Carlo and multi-exposure assessment.

PubMed

Niizuma, Shun; Matsui, Yoshihiko; Ohno, Koichi; Itoh, Sadahiko; Matsushita, Taku; Shirasaki, Nobutaka

2013-10-01

Drinking water quality standard (DWQS) criteria for chemicals for which there is a threshold for toxicity are derived by allocating a fraction of tolerable daily intake (TDI) to exposure from drinking water. We conducted physiologically based pharmacokinetic model simulations for chloroform and have proposed an equation for total oral-equivalent potential intake via three routes (oral ingestion, inhalation, and dermal exposures), the biologically effective doses of which were converted to oral-equivalent potential intakes. The probability distributions of total oral-equivalent potential intake in Japanese people were estimated by Monte Carlo simulations. Even when the chloroform concentration in drinking water equaled the current DWQS criterion, there was sufficient margin between the intake and the TDI: the probability that the intake exceeded TDI was below 0.1%. If a criterion that the 95th percentile estimate equals the TDI is regarded as both providing protection to highly exposed persons and leaving a reasonable margin of exposure relative to the TDI, then the chloroform drinking water criterion could be a concentration of 0.11mg/L. This implies a daily intake equal to 34% of the TDI allocated to the oral intake (2L/d) of drinking water for typical adults. For the highly exposed persons, inhalation exposure via evaporation from water contributed 53% of the total intake, whereas dermal absorption contributed only 3%. Copyright © 2013 Elsevier Inc. All rights reserved.

The effect of student-centered and teacher-centered instruction with and without conceptual advocacy on biology students' misconceptions, achievement, attitudes toward science, and cognitive retention

NASA Astrophysics Data System (ADS)

Gallop, Roger Graham

The purpose of this study was to investigate the effect of student-centered and teacher-centered instructional strategies with and without conceptual advocacy (CA) on ninth-grade biology students' misconceptions (MIS), biology achievement (ACH), attitudes toward science (ATT), and cognitive retention of scientific method and measurement, spontaneous generation, and characteristics of living things. Students were purposively selected using intact classes and assigned to one of four treatment groups (i.e., student-centered instruction without CA, student-centered instruction with CA, teacher-centered instruction with CA, and teacher-centered instruction without CA). A modified quasi-experimental design was used in which students were not matched in the conventional sense but instead, groups were shown to be equivalent on the dependent measure via a pretest. A 5-day treatment implementation period addressed science conceptions under investigation. The treatment period was based on the number of class periods teachers at the target school actually spend teaching the biological concepts under investigation using traditional instruction. At the end of the treatment period, students were posttested using the Concepts in Biology instrument and Science Questionnaire. Eight weeks after the posttest, these instruments were administered again as a delayed posttest to determine cognitive retention of the correct biological conceptions and attitudes toward science. MANCOVA and follow-up univariate ANCOVA results indicated that student-centered instruction without CA (i.e., Group 1) did not have a significant effect on students' MIS, ACH, and ATT (F = .029, p = .8658; F = .002, p =.9688, F = .292, p = .5897, respectively). On the other hand, student-centered instruction with CA (i.e., Group 2) had a significant effect on students' MIS and ACH (F =10.33, p = .0016 and F = 10.17, p = .0017, respectively), but did not on ATT (F = .433, p = .5117). Teacher-centered instruction with CA (i.e., Group 3) had a significant effect on students' MIS in favor of Group 4 (i.e., control group) (F = 4.11, p = .0444), and did not have a significant effect on ACH and ATT (F = 1.83, p = .1777 and F = 1.89, p = .1709, respectively). Student gender and teacher gender did not have a significant effect on students' MIS, ACH, and ATT. In the cognitive retention model, there was no significant difference among the research factors relative to the 3 dependent measures.

In Vitro Studies on Space Radiation-Induced Delayed Genetic Responses: Shielding Effects

NASA Technical Reports Server (NTRS)

Kadhim, Munira A.; Green, Lora M.; Gridley, Daila S.; Murray, Deborah K.; Tran, Da Thao; Andres, Melba; Pocock, Debbie; Macdonald, Denise; Goodhead, Dudley T.; Moyers, Michael F.

2003-01-01

Understanding the radiation risks involved in spaceflight is of considerable importance, especially with the long-term occupation of ISS and the planned crewed exploration missions. Several independent causes may contribute to the overall risk to astronauts exposed to the complex space environment, such as exposure to GCR as well as SPES. Protons and high-Z energetic particles comprise the GCR spectrum and may exert considerable biological effects even at low fluence. There are also considerable uncertainties associated with secondary particle effects (e.g. HZE fragments, neutrons etc.). The interaction of protons and high-LET particles with biological materials at all levels of biological organization needs to be investigated fully in order to establish a scientific basis for risk assessment. The results of these types of investigation will foster the development of appropriately directed countermeasures. In this study, we compared the biological responses to proton irradiation presented to the target cells as a monoenergetic beam of particles of complex composition delivered to cells outside or inside a tissue phantom head placed in the United States EVA space suit helmet. Measurements of chromosome aberrations, apoptosis, and the induction of key proteins were made in bone marrow from CBA/CaJ and C57BL/6 mice at early and late times post exposure to radiation at 0, 0.5, 1 and 2 Gy while inside or outside of the helmet. The data showed that proton irradiation induced transmissible chromosomal/genomic instability in haematopoietic stem cells in both strains of mice under both irradiation conditions and especially at low doses. Although differences were noted between the mouse strains in the degree and kinetics of transforming growth factor-beta 1 and tumor necrosis factor-alpha secretion, there were no significant differences observed in the level of the induced instability under either radiation condition, or for both strains of mice. Consequently, when normalized to physical dose, the monoenergetic proton field present inside the helmet-protected phantom produced equivalent biological responses, when compared to unshielded cells, as measured by the induction of delayed genetic effects in murine haematopoietic stem cells.

Essential Properties of Language, or, Why Language Is Not a Code

ERIC Educational Resources Information Center

Kravchenko, Alexander V.

2007-01-01

Despite a strong tradition of viewing "coded equivalence" as the underlying principle of linguistic semiotics, it lacks the power needed to understand and explain language as an empirical phenomenon characterized by complex dynamics. Applying the biology of cognition to the nature of the human cognitive/linguistic capacity as rooted in the…

Critical dose and toxicity index of organs at risk in radiotherapy: Analyzing the calculated effects of modified dose fractionation in non–small cell lung cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pedicini, Piernicola, E-mail: ppiern@libero.it; Strigari, Lidia; Benassi, Marcello

2014-04-01

To increase the efficacy of radiotherapy for non–small cell lung cancer (NSCLC), many schemes of dose fractionation were assessed by a new “toxicity index” (I), which allows one to choose the fractionation schedules that produce less toxic treatments. Thirty-two patients affected by non resectable NSCLC were treated by standard 3-dimensional conformal radiotherapy (3DCRT) with a strategy of limited treated volume. Computed tomography datasets were employed to re plan by simultaneous integrated boost intensity-modulated radiotherapy (IMRT). The dose distributions from plans were used to test various schemes of dose fractionation, in 3DCRT as well as in IMRT, by transforming the dose-volumemore » histogram (DVH) into a biological equivalent DVH (BDVH) and by varying the overall treatment time. The BDVHs were obtained through the toxicity index, which was defined for each of the organs at risk (OAR) by a linear quadratic model keeping an equivalent radiobiological effect on the target volume. The less toxic fractionation consisted in a severe/moderate hyper fractionation for the volume including the primary tumor and lymph nodes, followed by a hypofractionation for the reduced volume of the primary tumor. The 3DCRT and IMRT resulted, respectively, in 4.7% and 4.3% of dose sparing for the spinal cord, without significant changes for the combined-lungs toxicity (p < 0.001). Schedules with reduced overall treatment time (accelerated fractionations) led to a 12.5% dose sparing for the spinal cord (7.5% in IMRT), 8.3% dose sparing for V{sub 20} in the combined lungs (5.5% in IMRT), and also significant dose sparing for all the other OARs (p < 0.001). The toxicity index allows to choose fractionation schedules with reduced toxicity for all the OARs and equivalent radiobiological effect for the tumor in 3DCRT, as well as in IMRT, treatments of NSCLC.« less

Effective radiation reduction in Space Station and missions beyond the magnetosphere

NASA Technical Reports Server (NTRS)

Jordan, Thomas M.; Stassinopoulos, E. G.

1989-01-01

This paper investigates the efficiency of low- and high-atomic number materials used as protective shields against biologically effective radiation in doses equivalent to those expected in low-earth-orbit and interplanetary manned missions. Results are presented on calculations for single-material shields from polyethylene, water, Be, Al, Fe, and Ta and multilayer shelds made from the combinations of any two or any three of these materials, for both LEO and interplanetary conditions. It is shown that, whereas for protons and Galactic cosmic rays the ordering of shield materials has a negligible effect, for electrons and secondary bremsstrahlung, both the order and the composition are important parameters. It was found that low-atomic-number materials are most effective shields against protons and galactic cosmic rays, and are most effective in decreasing bremsstrahlung production, while high-atomic-number shields are the best attenuators of both primary electrons (if the dose is dominated by primary electrons) and secondary bremsstrahlung (if this is produced).

An equivalent viscoelastic model for rock mass with parallel joints

NASA Astrophysics Data System (ADS)

Li, Jianchun; Ma, Guowei; Zhao, Jian

2010-03-01

An equivalent viscoelastic medium model is proposed for rock mass with parallel joints. A concept of "virtual wave source (VWS)" is proposed to take into account the wave reflections between the joints. The equivalent model can be effectively applied to analyze longitudinal wave propagation through discontinuous media with parallel joints. Parameters in the equivalent viscoelastic model are derived analytically based on longitudinal wave propagation across a single rock joint. The proposed model is then verified by applying identical incident waves to the discontinuous and equivalent viscoelastic media at one end to compare the output waves at the other end. When the wavelength of the incident wave is sufficiently long compared to the joint spacing, the effect of the VWS on wave propagation in rock mass is prominent. The results from the equivalent viscoelastic medium model are very similar to those determined from the displacement discontinuity method. Frequency dependence and joint spacing effect on the equivalent viscoelastic model and the VWS method are discussed.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cederkrantz, Elin; Andersson, Håkan; Bernhardt, Peter

Purpose: Ovarian cancer is often diagnosed at an advanced stage with dissemination in the peritoneal cavity. Most patients achieve clinical remission after surgery and chemotherapy, but approximately 70% eventually experience recurrence, usually in the peritoneal cavity. To prevent recurrence, intraperitoneal (i.p.) targeted α therapy has been proposed as an adjuvant treatment for minimal residual disease after successful primary treatment. In the present study, we calculated absorbed and relative biological effect (RBE)-weighted (equivalent) doses in relevant normal tissues and estimated the effective dose associated with i.p. administration of {sup 211}At-MX35 F(ab'){sub 2}. Methods and Materials: Patients in clinical remission after salvage chemotherapymore » for peritoneal recurrence of ovarian cancer underwent i.p. infusion of {sup 211}At-MX35 F(ab'){sub 2}. Potassium perchlorate was given to block unwanted accumulation of {sup 211}At in thyroid and other NIS-containing tissues. Mean absorbed doses to normal tissues were calculated from clinical data, including blood and i.p. fluid samples, urine, γ-camera images, and single-photon emission computed tomography/computed tomography images. Extrapolation of preclinical biodistribution data combined with clinical blood activity data allowed us to estimate absorbed doses in additional tissues. The equivalent dose was calculated using an RBE of 5 and the effective dose using the recommended weight factor of 20. All doses were normalized to the initial activity concentration of the infused therapy solution. Results: The urinary bladder, thyroid, and kidneys (1.9, 1.8, and 1.7 mGy per MBq/L) received the 3 highest estimated absorbed doses. When the tissue-weighting factors were applied, the largest contributors to the effective dose were the lungs, stomach, and urinary bladder. Using 100 MBq/L, organ equivalent doses were less than 10% of the estimated tolerance dose. Conclusion: Intraperitoneal {sup 211}At-MX35 F(ab'){sub 2} treatment is potentially a well-tolerated therapy for locally confined microscopic ovarian cancer. Absorbed doses to normal organs are low, but because the effective dose potentially corresponds to a risk of treatment-induced carcinogenesis, optimization may still be valuable.« less

The toxicity of aluminium in humans.

PubMed

Exley, C

2016-06-01

We are living in the 'aluminium age'. Human exposure to aluminium is inevitable and, perhaps, inestimable. Aluminium's free metal cation, Alaq(3+), is highly biologically reactive and biologically available aluminium is non-essential and essentially toxic. Biologically reactive aluminium is present throughout the human body and while, rarely, it can be acutely toxic, much less is understood about chronic aluminium intoxication. Herein the question is asked as to how to diagnose aluminium toxicity in an individual. While there are as yet, no unequivocal answers to this problem, there are procedures to follow to ascertain the nature of human exposure to aluminium. It is also important to recognise critical factors in exposure regimes and specifically that not all forms of aluminium are toxicologically equivalent and not all routes of exposure are equivalent in their delivery of aluminium to target sites. To ascertain if Alzheimer's disease is a symptom of chronic aluminium intoxication over decades or breast cancer is aggravated by the topical application of an aluminium salt or if autism could result from an immune cascade initiated by an aluminium adjuvant requires that each of these is considered independently and in the light of the most up to date scientific evidence. The aluminium age has taught us that there are no inevitabilities where chronic aluminium toxicity is concerned though there are clear possibilities and these require proving or discounting but not simply ignored. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Where next for the reproducibility agenda in computational biology?

PubMed

Lewis, Joanna; Breeze, Charles E; Charlesworth, Jane; Maclaren, Oliver J; Cooper, Jonathan

2016-07-15

The concept of reproducibility is a foundation of the scientific method. With the arrival of fast and powerful computers over the last few decades, there has been an explosion of results based on complex computational analyses and simulations. The reproducibility of these results has been addressed mainly in terms of exact replicability or numerical equivalence, ignoring the wider issue of the reproducibility of conclusions through equivalent, extended or alternative methods. We use case studies from our own research experience to illustrate how concepts of reproducibility might be applied in computational biology. Several fields have developed 'minimum information' checklists to support the full reporting of computational simulations, analyses and results, and standardised data formats and model description languages can facilitate the use of multiple systems to address the same research question. We note the importance of defining the key features of a result to be reproduced, and the expected agreement between original and subsequent results. Dynamic, updatable tools for publishing methods and results are becoming increasingly common, but sometimes come at the cost of clear communication. In general, the reproducibility of computational research is improving but would benefit from additional resources and incentives. We conclude with a series of linked recommendations for improving reproducibility in computational biology through communication, policy, education and research practice. More reproducible research will lead to higher quality conclusions, deeper understanding and more valuable knowledge.

Radiation Genetics in Wheat, VI

DOE Office of Scientific and Technical Information (OSTI.GOV)

MATSUMURA, Seiji

1961-01-01

The thermal and fast neutron irradiations of dormant seeds of Triticum monococcum flavescens were conducted in the Japan Atomic Energy Research Institute's Nuclear Reactor, JRR-1, and in the Oak Ridge National Laboratory's accelerator (14 Mev), respectively. The higher the dosage of the thermal and fast neutrons, the more delayed were germination and growth of seedlings. The seeds were almost uniformly injured in each treatment. There was almost no germination at 37.5 x 10 12 n th/cm 2 of thermal neutrons and at 5 krad fast neutrons. Even at about 30 x 10 12 n th/cm 2 and at 2.5 kradmore » the seedlings did not grow and died in early stage. Also the higher the dosage, the more reduced were survival rate, height of mature plants, and seed fertility. The frequency of chromosome aberrations and chlorophyll and other mutations increased with the increase of dosage, as expected. In comparison with the resuils obtained from x and gamma-irradiations, 1 r equivalent effects of x rays are produced by about 2 x 10 9 n th/cm 2 of thermal neutrons for seedling length and seed fertility. Also the 1 r equivalent effects correspond roughly to those of the order of 10 n th/cm 2 for chromosome aberrations and chlorophyll mutations. The relative biological effectiveness (RBE) of fast neutrons to x rays was found to be for germination rate 4, for seedling length 10, for seed fertility 12, for chromosome aberrations 8, and for chlorophyll mutations 10.« less

Part II: Biomechanical assessment for a footprint-restoring transosseous-equivalent rotator cuff repair technique compared with a double-row repair technique.

PubMed

Park, Maxwell C; Tibone, James E; ElAttrache, Neal S; Ahmad, Christopher S; Jun, Bong-Jae; Lee, Thay Q

2007-01-01

We hypothesized that a transosseous-equivalent repair would demonstrate improved tensile strength and gap formation between the tendon and tuberosity when compared with a double-row technique. In 6 fresh-frozen human shoulders, a transosseous-equivalent rotator cuff repair was performed: a suture limb from each of two medial anchors was bridged over the tendon and fixed laterally with an interference screw. In 6 contralateral matched-pair specimens, a double-row repair was performed. For all repairs, a materials testing machine was used to load each repair cyclically from 10 N to 180 N for 30 cycles; each repair underwent tensile testing to measure failure loads at a deformation rate of 1 mm/sec. Gap formation between the tendon edge and insertion was measured with a video digitizing system. The mean ultimate load to failure was significantly greater for the transosseous-equivalent technique (443.0 +/- 87.8 N) compared with the double-row technique (299.2 +/- 52.5 N) (P = .043). Gap formation during cyclic loading was not significantly different between the transosseous-equivalent and double-row techniques, with mean values of 3.74 +/- 1.51 mm and 3.79 +/- 0.68 mm, respectively (P = .95). Stiffness for all cycles was not statistically different between the two constructs (P > .40). The transosseous-equivalent rotator cuff repair technique improves ultimate failure loads when compared with a double-row technique. Gap formation is similar for both techniques. A transosseous-equivalent repair helps restore footprint dimensions and provides a stronger repair than the double-row technique, which may help optimize healing biology.

Human exposure to large solar particle events in space

NASA Technical Reports Server (NTRS)

Townsend, L. W.; Wilson, J. W.; Shinn, J. L.; Curtis, S. B.

1992-01-01

Whenever energetic solar protons produced by solar particle events traverse bulk matter, they undergo various nuclear and atomic collision processes which significantly alter the physical characteristics and biologically important properties of their transported radiation fields. These physical interactions and their effect on the resulting radiation field within matter are described within the context of a recently developed deterministic, coupled neutron-proton space radiation transport computer code (BRYNTRN). Using this computer code, estimates of human exposure in interplanetary space, behind nominal (2 g/sq cm) and storm shelter (20 g/sq cm) thicknesses of aluminum shielding, are made for the large solar proton event of August 1972. Included in these calculations are estimates of cumulative exposures to the skin, ocular lens, and bone marrow as a function of time during the event. Risk assessment in terms of absorbed dose and dose equivalent is discussed for these organs. Also presented are estimates of organ exposures for hypothetical, worst-case flare scenarios. The rate of dose equivalent accumulation places this situation in an interesting region of dose rate between the very low values of usual concern in terrestrial radiation environments and the high-dose-rate values prevalent in radiation therapy.

Radiation burdens for humans on prolonged exomagnetospheric voyages.

PubMed

Moore, F D

1992-03-01

The severity of radiation exposure for astronauts outside the magnetosphere poses a critical unanswered question bearing on the use of manned vehicles in extended exploration of the solar system (moon, Mars). Such prolonged exomagnetospheric voyages (1-3 years) enter a radiologic environment more severe than that of low earth orbit, an annual dose equivalent in the range of 0.3-0.5 Sv (30-50 rem), and a lifetime excess cancer fatality risk of 3-5% due to low linear-energy-transfer components of galactic cosmic radiation alone. To this calculus must be added estimates for high-atomic-number, high-energy particles, the probability of solar particle events, and the limited effectiveness of shielding. For a 3-year Mars voyage these could elevate the dose equivalent to 1.5-2.25 Sv (150-225 rem) total (0.5-0.75 Sv [50-75 rem] annual) and risks to 5-9% excess cancer fatality. Both the mission (civilian scientific research) and the alternatives (unmanned robotic devices) enter the policy decision here. This paper presents a brief review of pertinent physical and biological data and of research urgently needed before reaching a decision on this question.

A comparative appraisal of two equivalence tests for multiple standardized effects.

PubMed

Shieh, Gwowen

2016-04-01

Equivalence testing is recommended as a better alternative to the traditional difference-based methods for demonstrating the comparability of two or more treatment effects. Although equivalent tests of two groups are widely discussed, the natural extensions for assessing equivalence between several groups have not been well examined. This article provides a detailed and schematic comparison of the ANOVA F and the studentized range tests for evaluating the comparability of several standardized effects. Power and sample size appraisals of the two grossly distinct approaches are conducted in terms of a constraint on the range of the standardized means when the standard deviation of the standardized means is fixed. Although neither method is uniformly more powerful, the studentized range test has a clear advantage in sample size requirements necessary to achieve a given power when the underlying effect configurations are close to the priori minimum difference for determining equivalence. For actual application of equivalence tests and advance planning of equivalence studies, both SAS and R computer codes are available as supplementary files to implement the calculations of critical values, p-values, power levels, and sample sizes. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Biological and dosimetric characterisation of spatially fractionated proton minibeams

NASA Astrophysics Data System (ADS)

Meyer, Juergen; Stewart, Robert D.; Smith, Daniel; Eagle, James; Lee, Eunsin; Cao, Ning; Ford, Eric; Hashemian, Reza; Schuemann, Jan; Saini, Jatinder; Marsh, Steve; Emery, Robert; Dorman, Eric; Schwartz, Jeff; Sandison, George

2017-12-01

The biological effectiveness of proton beams varies with depth, spot size and lateral distance from the beam central axis. The aim of this work is to incorporate proton relative biological effectiveness (RBE) and equivalent uniform dose (EUD) considerations into comparisons of broad beam and highly modulated proton minibeams. A Monte Carlo model of a small animal proton beamline is presented. Dose and variable RBE is calculated on a per-voxel basis for a range of energies (30-109 MeV). For an open beam, the RBE values at the beam entrance ranged from 1.02-1.04, at the Bragg peak (BP) from 1.3 to 1.6, and at the distal end of the BP from 1.4 to 2.0. For a 50 MeV proton beam, a minibeam collimator designed to produce uniform dose at the depth of the BP peak, had minimal impact on the open beam RBE values at depth. RBE changes were observed near the surface when the collimator was placed flush with the irradiated object, due to a higher neutron contribution derived from proton interactions with the collimator. For proton minibeams, the relative mean RBE weighted entrance dose (RWD) was ~25% lower than the physical mean dose. A strong dependency of the EUD with fraction size was observed. For 20 Gy fractions, the EUD varied widely depending on the radiosensitivity of the cells. For radiosensitive cells, the difference was up to ~50% in mean dose and ~40% in mean RWD and the EUD trended towards the valley dose rather than the mean dose. For comparative studies of uniform dose with spatially fractionated proton minibeams, EUD derived from a per-voxel RWD distribution is recommended for biological assessments of reproductive cell survival and related endpoints.

Biological and dosimetric characterisation of spatially fractionated proton minibeams.

PubMed

Meyer, Juergen; Stewart, Robert D; Smith, Daniel; Eagle, James; Lee, Eunsin; Cao, Ning; Ford, Eric; Hashemian, Reza; Schuemann, Jan; Saini, Jatinder; Marsh, Steve; Emery, Robert; Dorman, Eric; Schwartz, Jeff; Sandison, George

2017-11-21

The biological effectiveness of proton beams varies with depth, spot size and lateral distance from the beam central axis. The aim of this work is to incorporate proton relative biological effectiveness (RBE) and equivalent uniform dose (EUD) considerations into comparisons of broad beam and highly modulated proton minibeams. A Monte Carlo model of a small animal proton beamline is presented. Dose and variable RBE is calculated on a per-voxel basis for a range of energies (30-109 MeV). For an open beam, the RBE values at the beam entrance ranged from 1.02-1.04, at the Bragg peak (BP) from 1.3 to 1.6, and at the distal end of the BP from 1.4 to 2.0. For a 50 MeV proton beam, a minibeam collimator designed to produce uniform dose at the depth of the BP peak, had minimal impact on the open beam RBE values at depth. RBE changes were observed near the surface when the collimator was placed flush with the irradiated object, due to a higher neutron contribution derived from proton interactions with the collimator. For proton minibeams, the relative mean RBE weighted entrance dose (RWD) was ~25% lower than the physical mean dose. A strong dependency of the EUD with fraction size was observed. For 20 Gy fractions, the EUD varied widely depending on the radiosensitivity of the cells. For radiosensitive cells, the difference was up to ~50% in mean dose and ~40% in mean RWD and the EUD trended towards the valley dose rather than the mean dose. For comparative studies of uniform dose with spatially fractionated proton minibeams, EUD derived from a per-voxel RWD distribution is recommended for biological assessments of reproductive cell survival and related endpoints.

Completing and Adapting Models of Biological Processes

NASA Technical Reports Server (NTRS)

Margaria, Tiziana; Hinchey, Michael G.; Raffelt, Harald; Rash, James L.; Rouff, Christopher A.; Steffen, Bernhard

2006-01-01

We present a learning-based method for model completion and adaptation, which is based on the combination of two approaches: 1) R2D2C, a technique for mechanically transforming system requirements via provably equivalent models to running code, and 2) automata learning-based model extrapolation. The intended impact of this new combination is to make model completion and adaptation accessible to experts of the field, like biologists or engineers. The principle is briefly illustrated by generating models of biological procedures concerning gene activities in the production of proteins, although the main application is going to concern autonomic systems for space exploration.

Integration of different data gap filling techniques to facilitate ...

EPA Pesticide Factsheets

Data gap filling techniques are commonly used to predict hazard in the absence of empirical data. The most established techniques are read-across, trend analysis and quantitative structure-activity relationships (QSARs). Toxic equivalency factors (TEFs) are less frequently used data gap filling techniques which are applied to estimate relative potencies for mixtures of chemicals that contribute to an adverse outcome through a common biological target. For example, The TEF approach has been used for dioxin-like effects comparing individual chemical activity to that of the most toxic dioxin: 2,3,7,8-tetrachlorodibenzo-p-dioxin. The aim of this case study was to determine whether integration of two data gap filling techniques: QSARs and TEFs improved the predictive outcome for the assessment of a set of polychlorinated biphenyl (PCB) congeners and their mixtures. PCBs are associated with many different adverse effects, including their potential for neurotoxicity, which is the endpoint of interest in this study. The dataset comprised 209 PCB congeners, out of which 87 altered in vitro Ca(2+) homeostasis from which neurotoxic equivalency values (NEQs) were derived. The preliminary objective of this case study was to develop a QSAR model to predict NEQ values for the 122 untested PCB congeners. A decision tree model was developed using the number of position specific chlorine substitutions on the biphenyl scaffold as a fingerprint descriptor. Three different positiona

Morphogenesis and Cell Fate Determination within the Adaxial Cell Equivalence Group of the Zebrafish Myotome

PubMed Central

Nguyen-Chi, Mai E.; Bryson-Richardson, Robert; Sonntag, Carmen; Hall, Thomas E.; Gibson, Abigail; Sztal, Tamar; Chua, Wendy; Schilling, Thomas F.; Currie, Peter D.

2012-01-01

One of the central questions of developmental biology is how cells of equivalent potential—an equivalence group—come to adopt specific cellular fates. In this study we have used a combination of live imaging, single cell lineage analyses, and perturbation of specific signaling pathways to dissect the specification of the adaxial cells of the zebrafish embryo. We show that the adaxial cells are myogenic precursors that form a cell fate equivalence group of approximately 20 cells that consequently give rise to two distinct sub-types of muscle fibers: the superficial slow muscle fibers (SSFs) and muscle pioneer cells (MPs), distinguished by specific gene expression and cell behaviors. Using a combination of live imaging, retrospective and indicative fate mapping, and genetic studies, we show that MP and SSF precursors segregate at the beginning of segmentation and that they arise from distinct regions along the anterior-posterior (AP) and dorsal-ventral (DV) axes of the adaxial cell compartment. FGF signaling restricts MP cell fate in the anterior-most adaxial cells in each somite, while BMP signaling restricts this fate to the middle of the DV axis. Thus our results reveal that the synergistic actions of HH, FGF, and BMP signaling independently create a three-dimensional (3D) signaling milieu that coordinates cell fate within the adaxial cell equivalence group. PMID:23133395

Optimizing Equivalence-Based Instruction: Effects of Training Protocols on Equivalence Class Formation

ERIC Educational Resources Information Center

Fienup, Daniel M.; Wright, Nicole A.; Fields, Lanny

2015-01-01

Two experiments evaluated the effects of the simple-to-complex and simultaneous training protocols on the formation of academically relevant equivalence classes. The simple-to-complex protocol intersperses derived relations probes with training baseline relations. The simultaneous protocol conducts all training trials and test trials in separate…

10 CFR 835.702 - Individual monitoring records.

Code of Federal Regulations, 2010 CFR

2010-01-01

... emergency exposures. (b) Recording of the non-uniform equivalent dose to the skin is not required if the... internal dose (committed effective dose or committed equivalent dose) is not required for any monitoring...: (i) The effective dose from external sources of radiation (equivalent dose to the whole body may be...

10 CFR 835.702 - Individual monitoring records.

Code of Federal Regulations, 2011 CFR

2011-01-01

... emergency exposures. (b) Recording of the non-uniform equivalent dose to the skin is not required if the... internal dose (committed effective dose or committed equivalent dose) is not required for any monitoring...: (i) The effective dose from external sources of radiation (equivalent dose to the whole body may be...

10 CFR 835.702 - Individual monitoring records.

Code of Federal Regulations, 2014 CFR

2014-01-01

... emergency exposures. (b) Recording of the non-uniform equivalent dose to the skin is not required if the... internal dose (committed effective dose or committed equivalent dose) is not required for any monitoring...: (i) The effective dose from external sources of radiation (equivalent dose to the whole body may be...

10 CFR 835.702 - Individual monitoring records.

Code of Federal Regulations, 2013 CFR

2013-01-01

... emergency exposures. (b) Recording of the non-uniform equivalent dose to the skin is not required if the... internal dose (committed effective dose or committed equivalent dose) is not required for any monitoring...: (i) The effective dose from external sources of radiation (equivalent dose to the whole body may be...

10 CFR 835.702 - Individual monitoring records.

Code of Federal Regulations, 2012 CFR

2012-01-01

... emergency exposures. (b) Recording of the non-uniform equivalent dose to the skin is not required if the... internal dose (committed effective dose or committed equivalent dose) is not required for any monitoring...: (i) The effective dose from external sources of radiation (equivalent dose to the whole body may be...

Using synthetic biology to make cells tomorrow's test tubes.

PubMed

Garcia, Hernan G; Brewster, Robert C; Phillips, Rob

2016-04-18

The main tenet of physical biology is that biological phenomena can be subject to the same quantitative and predictive understanding that physics has afforded in the context of inanimate matter. However, the inherent complexity of many of these biological processes often leads to the derivation of complex theoretical descriptions containing a plethora of unknown parameters. Such complex descriptions pose a conceptual challenge to the establishment of a solid basis for predictive biology. In this article, we present various exciting examples of how synthetic biology can be used to simplify biological systems and distill these phenomena down to their essential features as a means to enable their theoretical description. Here, synthetic biology goes beyond previous efforts to engineer nature and becomes a tool to bend nature to understand it. We discuss various recent and classic experiments featuring applications of this synthetic approach to the elucidation of problems ranging from bacteriophage infection, to transcriptional regulation in bacteria and in developing embryos, to evolution. In all of these examples, synthetic biology provides the opportunity to turn cells into the equivalent of a test tube, where biological phenomena can be reconstituted and our theoretical understanding put to test with the same ease that these same phenomena can be studied in the in vitro setting.

Biological and nonbiological complex drugs for multiple sclerosis in Latin America: regulations and risk management.

PubMed

Carrá, Adriana; Macías Islas, Miguel Angel; Tarulla, Adriana; Bichuetti, Denis Bernardi; Finkelsztejn, Alessandro; Fragoso, Yara Dadalti; Árcega-Revilla, Raul; Cárcamo Rodríguez, Claudia; Durán, Juan Carlos; Bonitto, Juan García; León, Rosalba; Oehninger Gatti, Carlos; Orozco, Geraldine; Vizcarra Escobar, Darwin

2015-06-01

Biological drugs and nonbiological complex drugs with expired patents are followed by biosimilars and follow-on drugs that are supposedly similar and comparable with the reference product in terms of quality, safety and efficacy. Unlike simple molecules that can be copied and reproduced, biosimilars and follow-on complex drugs are heterogeneous and need specific regulations from health and pharmacovigilance agencies. A panel of 14 Latin American experts on multiple sclerosis from nine different countries met to discuss the recommendations regarding biosimilars and follow-on complex drugs for treating multiple sclerosis. Specific measures relating to manufacturing, therapeutic equivalence assessment and pharmacovigilance reports need to be implemented before commercialization. Physical, chemical, biological and immunogenic characterizations of the new product need to be available before clinical trials start. The new product must maintain the same immunogenicity as the original. Automatic substitution of biological and complex drugs poses unacceptable risks to the patient.

The Fourier analysis of biological transients.

PubMed

Harris, C M

1998-08-31

With modern computing technology the digital implementation of the Fourier transform is widely available, mostly in the form of the fast Fourier transform (FFT). Although the FFT has become almost synonymous with the Fourier transform, it is a fast numerical technique for computing the discrete Fourier transform (DFT) of a finite sequence of sampled data. The DFT is not directly equivalent to the continuous Fourier transform of the underlying biological signal, which becomes important when analyzing biological transients. Although this distinction is well known by some, for many it leads to confusion in how to interpret the FFT of biological data, and in how to precondition data so as to yield a more accurate Fourier transform using the FFT. We review here the fundamentals of Fourier analysis with emphasis on the analysis of transient signals. As an example of a transient, we consider the human saccade to illustrate the pitfalls and advantages of various Fourier analyses.

Kinetics and dosimetry of thallium-201 in human testes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rao, D.V.; Shepstone, B.J.; Wilkins, H.B.

Thallous chloride ({sup 201}Tl) is a well-known imaging agent. It has been shown to accumulate in the testes. In view of this, the testicular kinetics of {sup 201}Tl is investigated in humans and the absorbed dose to the organ calculated. Thallous chloride {sup 201}Tl was injected intravenously into four patients for myocardial perfusion studies. After clinical evaluation, the testicular uptake and clearance of {sup 201}Tl were monitored for about 1 wk using a gamma camera. Testicular uptake of {sup 201}Tl was rapid with a mean biological uptake half-time of 0.67 hr and mean biological clearance half-time of 280 hr. Themore » mean maximum testicular uptake of {sup 201}Tl was about 0.4% of the injected activity. These data were utilized to calculate the average absorbed dose to the testes. The absorbed dose to the testes was calculated to be 3.5 x 10{sup {minus}4} Gy/MBq (1.3 rad/mCi) of injected activity. When the relative biological effectiveness of the Auger emitter {sup 201}Tl is taken into account, the equivalent dose to the testes is 9.5 x 10{sup {minus}4} Sv/MBq (3.5 rem/mCi). 14 refs., 1 fig., 2 tabs.« less

"Rinse and trickle": a protocol for TEM preparation and investigation of inorganic fibers from biological material.

PubMed

Vigliaturo, Ruggero; Capella, Silvana; Rinaudo, Caterina; Belluso, Elena

2016-07-01

The purpose of this work is to define a sample preparation protocol that allows inorganic fibers and particulate matter extracted from different biological samples to be characterized morphologically, crystallographically and chemically by transmission electron microscopy-energy dispersive spectroscopy (TEM-EDS). The method does not damage or create artifacts through chemical attacks of the target material. A fairly rapid specimen preparation is applied with the aim of performing as few steps as possible to transfer the withdrawn inorganic matter onto the TEM grid. The biological sample is previously digested chemically by NaClO. The salt is then removed through a series of centrifugation and rinse cycles in deionized water, thus drastically reducing the digestive power of the NaClO and concentrating the fibers for TEM analysis. The concept of equivalent hydrodynamic diameter is introduced to calculate the settling velocity during the centrifugation cycles. This technique is applicable to lung tissues and can be extended to a wide range of organic materials. The procedure does not appear to cause morphological damage to the fibers or modify their chemistry or degree of crystallinity. The extrapolated data can be used in interdisciplinary studies to understand the pathological effects caused by inorganic materials.

Topical treatment with coenzyme Q10-containing formulas improves skin's Q10 level and provides antioxidative effects.

PubMed

Knott, Anja; Achterberg, Volker; Smuda, Christoph; Mielke, Heiko; Sperling, Gabi; Dunckelmann, Katja; Vogelsang, Alexandra; Krüger, Andrea; Schwengler, Helge; Behtash, Mojgan; Kristof, Sonja; Diekmann, Heike; Eisenberg, Tanya; Berroth, Andreas; Hildebrand, Janosch; Siegner, Ralf; Winnefeld, Marc; Teuber, Frank; Fey, Sven; Möbius, Janne; Retzer, Dana; Burkhardt, Thorsten; Lüttke, Juliane; Blatt, Thomas

2015-01-01

Ubiquinone (coenzyme Q10, Q10) represents an endogenously synthesized lipid-soluble antioxidant which is crucial for cellular energy production but is diminished with age and under the influence of external stress factors in human skin. Here, it is shown that topical Q10 treatment is beneficial with regard to effective Q10 replenishment, augmentation of cellular energy metabolism, and antioxidant effects. Application of Q10-containing formulas significantly increased the levels of this quinone on the skin surface. In the deeper layers of the epidermis the ubiquinone level was significantly augmented indicating effective supplementation. Concurrent elevation of ubiquinol levels suggested metabolic transformation of ubiquinone resulting from increased energy metabolism. Incubation of cultured human keratinocytes with Q10 concentrations equivalent to treated skin showed a significant augmentation of energy metabolism. Moreover, the results demonstrated that stressed skin benefits from the topical Q10 treatment by reduction of free radicals and an increase in antioxidant capacity. © 2015 International Union of Biochemistry and Molecular Biology.

10 CFR 33.15 - Requirements for the issuance of a Type C specific license of broad scope.

Code of Federal Regulations, 2010 CFR

2010-01-01

... OF BROAD SCOPE FOR BYPRODUCT MATERIAL Specific Licenses of Broad Scope § 33.15 Requirements for the... this chapter; and (b) The applicant submits a statement that byproduct material will be used only by... bachelor level, or equivalent training and experience, in the physical or biological sciences or in...

Use of Threshold of Toxicological Concern (TTC) with High Throughput Exposure Predictions as a Risk-Based Screening Approach of Several Thousand Commodity Chemicals (SOT Poster)

EPA Science Inventory

Although progress has been made with HTS (high throughput screening) in profiling biological activity (e.g., EPA’s ToxCast™), challenges arise interpreting HTS results in the context of adversity & converting HTS assay concentrations to equivalent human doses for the broad domain...

Staff Scientist - RNA Bioinformatics | Center for Cancer Research

Cancer.gov

The newly established RNA Biology Laboratory (RBL) at the Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH) in Frederick, Maryland is recruiting a Staff Scientist with strong expertise in RNA bioinformatics to join the Intramural Research Program’s mission of high impact, high reward science. The RBL is the equivalent of an

Combining the LKB NTCP model with radiosensitivity parameters to characterize toxicity of radionuclides based on a multiclonogen kidney model: a theoretical assessment.

PubMed

Lin, Hui; Jing, Jia; Xu, Liangfeng; Wu, Dongsheng; Xu, Yuanying

2012-06-01

The Lyman-Kutcher-Burman (LKB) normal tissue complication probability (NTCP) model is often used to estimate the damage level to normal tissue. However, it does not manifestly involve the influence of radiosensitivity parameters. This work replaces the generalized mean equivalent uniform dose (gEUD) with the equivalent uniform dose (EUD) in the LKB model to investigate the effect of a variety of radiobiological parameters on the NTCP to characterize the toxicity of five types of radionuclides. The dose for 50 % complication probability (D (50)) is replaced by the corresponding EUD for 50 % complication probability (EUD(50)). The properties of a variety of radiobiological characteristics, such as biologically effective dose (BED), NTCP, and EUD, for five types of radioisotope ((131)I, (186)Re, (188)Re, (90)Y, and (67)Cu) are investigated by various radiosensitivity parameters such as intrinsic radiosensitivity α, alpha-beta ratio α/β, cell repair half-time, cell mean clonogen doubling time, etc. The high-energy beta emitters ((90)Y and (188)Re) have high initial dose rate and mean absorbed dose per injected activity in kidney, and their kidney toxicity should be of greater concern if they are excreted through kidneys. The radiobiological effect of (188)Re changes most sharply with the radiobiological parameters due to its high-energy electrons and very short physical half-life. The dose for a probability of 50% injury within 5y (D (50/5)) 28 Gy for whole-kidney irradiation should be adjusted according to different radionuclides and different radiosensitivity of individuals. The D (50/5) of individuals with low α/β or low α, or low biological clearance half-time, will be less than 28 Gy. The 50 % complication probability dose for (67)Cu and (188)Re could be 25 Gy and 22 Gy. The same mean absorbed dose generally corresponds to different degrees of damage for tissues of different radiosensitivity and different radionuclides. The influence of various radiobiological parameters should be taken into consideration in the NTCP model.

Evaluation of the removal of antiestrogens and antiandrogens via ozone and granular activated carbon using bioassay and fluorescent spectroscopy.

PubMed

Ma, Dehua; Chen, Lujun; Wu, Yuchao; Liu, Rui

2016-06-01

Antiestrogens and antiandrogens are relatively rarely studied endocrine disrupting chemicals which can be found in un/treated wastewaters. Antiestrogens and antiandrogens in the wastewater treatment effluents could contribute to sexual disruption of organisms. In this study, to assess the removal of non-specific antiestrogens and antiandrogens by advanced treatment processes, ozonation and adsorption to granular activated carbon (GAC), the biological activities and excitation emission matrix fluorescence spectroscopy of wastewater were evaluated. As the applied ozone dose increased to 12 mg/L, the antiestrogenic activity dramatically decreased to 3.2 μg 4-hydroxytamoxifen equivalent (4HEQ)/L, with a removal efficiency of 84.8%, while the antiandrogenic activity was 23.1 μg flutamide equivalent (FEQ)/L, with a removal efficiency of 75.5%. The removal of antiestrogenic/antiandrogenic activity has high correlation with the removal of fulvic acid-like materials and humic acid-like organics, suggesting that they can be used as surrogates for antiestrogenic/antiandrogenic activity during ozonation. The adsorption kinetics of antiestrogenic activity and antiandrogenic activity were well described by pseudo-second-order kinetics models. The estimated equilibrium concentration of antiestrogenic activity is 7.9 μg 4HEQ/L with an effective removal efficiency of 70.5%, while the equilibrium concentration of antiandrogenic activity is 33.7 μg FEQ/L with a removal efficiency of 67.0%. Biological activity evaluation of wastewater effluents is an attractive way to assess the removal of endocrine disrupting chemicals by different treatment processes. Fluorescence spectroscopy can be used as a surrogate measure of bioassays during ozonation. Copyright © 2016 Elsevier Ltd. All rights reserved.

An organ-based approach to dose calculation in the assessment of dose-dependent biological effects of ionising radiation in Arabidopsis thaliana.

PubMed

Biermans, Geert; Horemans, Nele; Vanhoudt, Nathalie; Vandenhove, Hildegarde; Saenen, Eline; Van Hees, May; Wannijn, Jean; Vives i Batlle, Jordi; Cuypers, Ann

2014-07-01

There is a need for a better understanding of biological effects of radiation exposure in non-human biota. Correct description of these effects requires a more detailed model of dosimetry than that available in current risk assessment tools, particularly for plants. In this paper, we propose a simple model for dose calculations in roots and shoots of Arabidopsis thaliana seedlings exposed to radionuclides in a hydroponic exposure setup. This model is used to compare absorbed doses for three radionuclides, (241)Am (α-radiation), (90)Sr (β-radiation) and (133)Ba (γ radiation). Using established dosimetric calculation methods, dose conversion coefficient values were determined for each organ separately based on uptake data from the different plant organs. These calculations were then compared to the DCC values obtained with the ERICA tool under equivalent geometry assumptions. When comparing with our new method, the ERICA tool appears to overestimate internal doses and underestimate external doses in the roots for all three radionuclides, though each to a different extent. These observations might help to refine dose-response relationships. The DCC values for (90)Sr in roots are shown to deviate the most. A dose-effect curve for (90)Sr β-radiation has been established on biomass and photosynthesis endpoints, but no significant dose-dependent effects are observed. This indicates the need for use of endpoints at the molecular and physiological scale. Copyright © 2013 Elsevier Ltd. All rights reserved.

Use of equivalent spheres to model the relation between radar reflectivity and optical extinction of ice cloud particles.

PubMed

Donovan, David Patrick; Quante, Markus; Schlimme, Ingo; Macke, Andreas

2004-09-01

The effect of ice crystal size and shape on the relation between radar reflectivity and optical extinction is examined. Discrete-dipole approximation calculations of 95-GHz radar reflectivity and ray-tracing calculations are applied to ice crystals of various habits and sizes. Ray tracing was used primarily to calculate optical extinction and to provide approximate information on the lidar backscatter cross section. The results of the combined calculations are compared with Mie calculations applied to collections of different types of equivalent spheres. Various equivalent sphere formulations are considered, including equivalent radar-lidar spheres; equivalent maximum dimension spheres; equivalent area spheres, and equivalent volume and equivalent effective radius spheres. Marked differences are found with respect to the accuracy of different formulations, and certain types of equivalent spheres can be used for useful prediction of both the radar reflectivity at 95 GHz and the optical extinction (but not lidar backscatter cross section) over a wide range of particle sizes. The implications of these results on combined lidar-radar ice cloud remote sensing are discussed.

RCT: Module 2.06, Air Sampling Program and Methods, Course 8772

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hillmer, Kurt T.

The inhalation of radioactive particles is the largest cause of an internal radiation dose. Airborne radioactivity measurements are necessary to ensure that the control measures are and continue to be effective. Regulations govern the allowable effective dose equivalent to an individual. The effective dose equivalent is determined by combining the external and internal dose equivalent values. Typically, airborne radioactivity levels are maintained well below allowable levels to keep the total effective dose equivalent small. This course will prepare the student with the skills necessary for RCT qualification by passing quizzes, tests, and the RCT Comprehensive Phase 1, Unit 2 Examinationmore » (TEST 27566) and will provide in-the-field skills.« less

Computational Transport Modeling of High-Energy Neutrons Found in the Space Environment

NASA Technical Reports Server (NTRS)

Cox, Brad; Theriot, Corey A.; Rohde, Larry H.; Wu, Honglu

2012-01-01

The high charge and high energy (HZE) particle radiation environment in space interacts with spacecraft materials and the human body to create a population of neutrons encompassing a broad kinetic energy spectrum. As an HZE ion penetrates matter, there is an increasing chance of fragmentation as penetration depth increases. When an ion fragments, secondary neutrons are released with velocities up to that of the primary ion, giving some neutrons very long penetration ranges. These secondary neutrons have a high relative biological effectiveness, are difficult to effectively shield, and can cause more biological damage than the primary ions in some scenarios. Ground-based irradiation experiments that simulate the space radiation environment must account for this spectrum of neutrons. Using the Particle and Heavy Ion Transport Code System (PHITS), it is possible to simulate a neutron environment that is characteristic of that found in spaceflight. Considering neutron dosimetry, the focus lies on the broad spectrum of recoil protons that are produced in biological targets. In a biological target, dose at a certain penetration depth is primarily dependent upon recoil proton tracks. The PHITS code can be used to simulate a broad-energy neutron spectrum traversing biological targets, and it account for the recoil particle population. This project focuses on modeling a neutron beamline irradiation scenario for determining dose at increasing depth in water targets. Energy-deposition events and particle fluence can be simulated by establishing cross-sectional scoring routines at different depths in a target. This type of model is useful for correlating theoretical data with actual beamline radiobiology experiments. Other work exposed human fibroblast cells to a high-energy neutron source to study micronuclei induction in cells at increasing depth behind water shielding. Those findings provide supporting data describing dose vs. depth across a water-equivalent medium. This poster presents PHITS data suggesting an increase in dose, up to roughly 10 cm depth, followed by a continual decrease as neutrons come to a stop in the target.

Occupational exposure to radon for underground tourist routes in Poland: Doses to lung and the risk of developing lung cancer.

PubMed

Walczak, Katarzyna; Olszewski, Jerzy; Politański, Piotr; Zmyślony, Marek

2017-07-14

Radon concentrations for 31 Polish underground tourist routes were analyzed. The equivalent dose to the lung, the effective dose and the relative risk were calculated for employees of the analyzed routes on the grounds of information on radon concentrations, work time, etc. The relative risk for lung cancers was calculated using the Biological Effects of Ionizing Radiation (BEIR) VI Committee model. Equivalent doses to the lungs of workers were determined using the coefficients calculated by the Kendall and Smith. The conversion coefficient proposed by the International Atomic Energy Agency (IAEA) in the report No. 33 was used for estimating the effective doses. In 13 routes, the effective dose was found to be above 1 mSv/year, and in 3 routes, it exceeded 6 mSv/year. For 5 routes, the equivalent dose to lungs was higher than 100 mSv/year, and in 1 case it was as high as 490 mSv/year. In 22.6% of underground workplaces the risk of developing lung cancer among employees was about 2 times higher than that for the general population, and for 1 tourist route it was about 5 times higher. The geometric mean of the relative risk of lung cancer for all workers of underground tourist routes was 1.73 (95% confidence interval (CI): 1.6-1.87). Routes were divided into: caves, mines, post-military underground constructions and urban underground constructions. The difference between levels of the relative risk of developing lung cancer for all types of underground tourist routes was not found to be significant. If we include the professional group of the employees of underground tourist routes into the group of occupational exposure, the number of persons who are included in the Category A due to occupational exposure may increase by about 3/4. The professional group of the employees of underground tourist routes should be monitored for their exposure to radon. Int J Occup Med Environ Health 2017;30(5):687-694. This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.

Effect of Patient Set-up and Respiration motion on Defining Biological Targets for Image-Guided Targeted Radiotherapy

NASA Astrophysics Data System (ADS)

McCall, Keisha C.

Identification and monitoring of sub-tumor targets will be a critical step for optimal design and evaluation of cancer therapies in general and biologically targeted radiotherapy (dose-painting) in particular. Quantitative PET imaging may be an important tool for these applications. Currently radiotherapy planning accounts for tumor motion by applying geometric margins. These margins create a motion envelope to encompass the most probable positions of the tumor, while also maintaining the appropriate tumor control and normal tissue complication probabilities. This motion envelope is effective for uniform dose prescriptions where the therapeutic dose is conformed to the external margins of the tumor. However, much research is needed to establish the equivalent margins for non-uniform fields, where multiple biological targets are present and each target is prescribed its own dose level. Additionally, the size of the biological targets and close proximity make it impractical to apply planning margins on the sub-tumor level. Also, the extent of high dose regions must be limited to avoid excessive dose to the surrounding tissue. As such, this research project is an investigation of the uncertainty within quantitative PET images of moving and displaced dose-painting targets, and an investigation of the residual errors that remain after motion management. This included characterization of the changes in PET voxel-values as objects are moved relative to the discrete sampling interval of PET imaging systems (SPECIFIC AIM 1). Additionally, the repeatability of PET distributions and the delineating dose-painting targets were measured (SPECIFIC AIM 2). The effect of imaging uncertainty on the dose distributions designed using these images (SPECIFIC AIM 3) has also been investigated. This project also included analysis of methods to minimize motion during PET imaging and reduce the dosimetric impact of motion/position-induced imaging uncertainty (SPECIFIC AIM 4).

The Potential Feasibility of Chlorinic Photosynthesis on Extrasolar Planets

NASA Astrophysics Data System (ADS)

Haas, Johnson

2009-09-01

It is highly likely that the first convincing evidence of extrasolar life will arrive in the form of atmospheric absorption spectra. The modern search for life-bearing extrasolar planets emphasizes the potential detection of O2 and O3 absorption spectra in exoplanetary atmospheres as archetypal signatures of biology. However, oxygenic photosynthesis apparently failed to evolve independently more than once on Earth, and is thus unlikely to be reliably ubiquitous throughout the universe. Alternative evolutionary paths may yield planetary atmospheres tinted with the waste products of other dominant metabolisms, including potentially exotic biochemistries. This study examines the potential feasibility of one such exotic metabolism: chlorinic photosynthesis (CPS), defined as biologically-mediated halogenation of aqueous chloride to HClO, Cl2 or partially-oxidized intermediates (e.g. haloalkanes, haloacids, haloaromatics), coupled with photosynthetic CO2 fixation. This metabolic couple is feasible thermodynamically and appears to be geochemically plausible under approximately terrestrial conditions. This study hypothesizes that planetary biospheres dominated by CPS would develop atmospheres enriched with dihalogens and other halogenated compounds, evolve a highly oxidizing surface geochemical environment, and foster biological selection pressures favoring halogen resistance and eventual metazoan heterotrophy based on dihalogen and halocarbon respiration. Planets favoring the evolution of CPS would probably receive equivalent or greater surface UV flux than Earth did in the Paleoarchean (promoting abiotic photo-oxidation of aqueous halides, and establishing a strong biological selective pressure toward their accommodation), and would orbit stars having equivalent or greater bulk metallicities (promoting greater planetary halide abundances) relative to the Sun. Directed searches for such worlds should probably focus on A, F and G0 spectral class stars having bulk metallicities of +0.0 Dex or greater.

Pereskia aculeata Muller (Cactaceae) Leaves: Chemical Composition and Biological Activities

PubMed Central

Souza, Lucèia Fàtima; Caputo, Lucia; Inchausti De Barros, Ingrid Bergman; Fratianni, Florinda; Nazzaro, Filomena; De Feo, Vincenzo

2016-01-01

The aims of this work were to study the chemical composition of the essential oil from the leaves of Pereskia aculeata and to evaluate some biological activities of three leaf extracts. The phenolic content, antioxidant activity, and in vitro antimicrobial and antifungal activities were determined. The methanol extract showed antioxidant activity (EC50 7.09 mg/mL) and high polyphenols content (15.04 ± 0.31 mg gallic acid equivalents (GAE)/g). The petroleum ether extract exhibited potent antibacterial activity against Escherichia coli, whereas the chloroform extract showed inhibitory activity against Bacillus cereus and Staphylococcus aureus. The petroleum ether and methanol extracts were more effective in inhibiting the growth of Aspergillus versicolor. The possible cytotoxicity of extracts on neuroblastoma SH-SY5Y cancer cell line and the influence on adenylate cyclase (ADCY) expression was also studied. P. aculeata chloroform extract showed antiproliferative activity with an IC50 value of 262.83 µg/mL. Treatments of SH-SY5Y neuroblastoma cells with 100 µg/mL of methanol extract significantly reduced ADCY1 expression. PMID:27598154

Selective extraction of halogenated compounds from data measured by comprehensive multidimensional gas chromatography/high resolution time-of-flight mass spectrometry for non-target analysis of environmental and biological samples.

PubMed

Hashimoto, Shunji; Zushi, Yasuyuki; Fushimi, Akihiro; Takazawa, Yoshikatsu; Tanabe, Kiyoshi; Shibata, Yasuyuki

2013-03-22

We developed a method that selectively extracts a subset from comprehensive 2D gas chromatography (GC×GC) and high-resolution time-of-flight mass spectrometry (HRTOFMS) data to detect and identify trace levels of organohalogens. The data were obtained by measuring several environmental and biological samples, namely fly ash, soil, sediment, the atmosphere, and human urine. For global analysis, some samples were measured without purification. By using our novel software, the mass spectra of organochlorines or organobromines were then extracted into a data subset under high mass accuracy conditions that were approximately equivalent to a mass resolution of 6000 for some samples. Mass defect filtering as pre-screening for the data extraction was very effective in removing the mass spectra of hydrocarbons. Those results showed that data obtained with HRTOFMS are valuable for global analysis of organohalogens, and probably of other compounds if specific data extraction methods can be devised. Copyright © 2013 Elsevier B.V. All rights reserved.

Pereskia aculeata Muller (Cactaceae) Leaves: Chemical Composition and Biological Activities.

PubMed

Souza, Lucèia Fàtima; Caputo, Lucia; Inchausti De Barros, Ingrid Bergman; Fratianni, Florinda; Nazzaro, Filomena; De Feo, Vincenzo

2016-09-03

The aims of this work were to study the chemical composition of the essential oil from the leaves of Pereskia aculeata and to evaluate some biological activities of three leaf extracts. The phenolic content, antioxidant activity, and in vitro antimicrobial and antifungal activities were determined. The methanol extract showed antioxidant activity (EC50 7.09 mg/mL) and high polyphenols content (15.04 ± 0.31 mg gallic acid equivalents (GAE)/g). The petroleum ether extract exhibited potent antibacterial activity against Escherichia coli, whereas the chloroform extract showed inhibitory activity against Bacillus cereus and Staphylococcus aureus. The petroleum ether and methanol extracts were more effective in inhibiting the growth of Aspergillus versicolor. The possible cytotoxicity of extracts on neuroblastoma SH-SY5Y cancer cell line and the influence on adenylate cyclase (ADCY) expression was also studied. P. aculeata chloroform extract showed antiproliferative activity with an IC50 value of 262.83 µg/mL. Treatments of SH-SY5Y neuroblastoma cells with 100 µg/mL of methanol extract significantly reduced ADCY1 expression.

In vitro study of biological activities of anthocyanin-rich berry extracts on porcine intestinal epithelial cells.

PubMed

Kšonžeková, Petra; Mariychuk, Ruslan; Eliašová, Adriana; Mudroňová, Dagmar; Csank, Tomáš; Király, Ján; Marcinčáková, Dana; Pistl, Juraj; Tkáčiková, L'udmila

2016-03-15

Anthocyanins, compounds that represent the major group of flavonoids in berries, are one of the most powerful natural antioxidants. The aim of this study was to evaluate biological activities and comparison of anthocyanin-rich extracts prepared from chokeberry (Aronia melanocarpa), elderberry (Sambucus nigra), bilberry (Vaccinium myrtillus) and blueberry (V. corymbosum) on the porcine intestinal epithelial IPEC-1 cell line. The IC50 values calculated in the antioxidant cell-based dichlorofluorescein assay (DCF assay) were 1.129 mg L(-1) for chokeberry, 1.081 mg L(-1) for elderberry, 2.561 mg L(-1) for bilberry and 2.965 mg L(-1) for blueberry, respectively. We found a significant negative correlation (P < 0.001) between cyanidin glycosides content and IC50 values. Moreover, extracts rich in cyanidin glycosides stimulated proliferation of IPEC-1 cells and did not have cytotoxic effect on cells at an equivalent in vivo concentration. We found that the chokeberry and elderberry extracts rich in cyanidin glycosides possess better antioxidant and anticytotoxic activities in comparison to blueberry or bilberry extracts with complex anthocyanin profiles. © 2015 Society of Chemical Industry.

A Multi-institution, Retrospective Analysis of Cervix Intracavitary Brachytherapy Treatments. Part 1: Is EQD2 Good Enough for Reporting Radiobiological Effects?

PubMed

Fields, Emma C; Melvani, Rakhi; Hajdok, George; D'Souza, David; Jones, Bernard; Stuhr, Kelly; Diot, Quentin; Fisher, Christine M; Mukhopadhyay, Nitai; Todor, Dorin

2017-09-01

When brachytherapy doses are reported or added, biologically effective dose (BED) minimum dose covering 90% of the volume (D90) is used as if dose is delivered uniformly to the target. Unlike BED(D90), equivalent uniform BED (EUBED) and generalized biologically equivalent uniform dose (gBEUD) are quantities that integrate dose inhomogeneity. Here we compared BED(D90) and equivalent uniform BED (EUBED)/gBEUD in 3 settings: (1) 2 sites using tandem and ovoid (T&O) but different styles of implants; (2) 2 sites using different devices-T&O and tandem and ring (T&R)-and different styles; and (3) the same site using T&O and T&R with the same style. EUBED and gBEUD were calculated for 260 fractions from 3 institutions using BED(α/β = 10 Gy). EUBED uses an extra parameter α with smaller values associated with radioresistant tumors. Similarly, gBEUD uses a, which places variable emphasis on hot/cold spots. Distributions were compared using the Kolmogorov-Smirnoff test at 5% significance. For the 2 sites using T&O, the distribution of EUBED-BED(D90) was not different for values of α = 0.5 to 0.3 Gy -1 but was statistically different for values of α = 0.15 to 0.05 Gy -1 (P=.01, .002). The mean percentage differences between EUBED and BED(D90) ranged from 20% to 100% for α = 0.5 Gy -1 to 0.05 Gy -1 . Using gBEUD-BED(D90), the P values indicate the distributions to be similar for a = -10 but to be significantly different for other values of a (-5, -1, 1). Between sites and at the same site using T&O versus T&R, the distributions were statistically different with EUBED/gBEUD irrespective of parameter values at which these quantities were computed. These differences indicate that EUBED/gBEUD capture differences between the techniques and applicators that are not detected by the BED(D90). BED(D90) is unable to distinguish between plans created by different devices or optimized differently. EUBED/gBEUD distinguish between dose distributions created by different devices and styles of implant and planning. This discrepancy is particularly important with the increased use of magnetic resonance imaging and hybrid devices, whereby one has the ability to create dose distributions that are significant departures from the classic pear. Copyright © 2017 Elsevier Inc. All rights reserved.

A modified Wright-Fisher model that incorporates Ne: A variant of the standard model with increased biological realism and reduced computational complexity.

PubMed

Zhao, Lei; Gossmann, Toni I; Waxman, David

2016-03-21

The Wright-Fisher model is an important model in evolutionary biology and population genetics. It has been applied in numerous analyses of finite populations with discrete generations. It is recognised that real populations can behave, in some key aspects, as though their size that is not the census size, N, but rather a smaller size, namely the effective population size, Ne. However, in the Wright-Fisher model, there is no distinction between the effective and census population sizes. Equivalently, we can say that in this model, Ne coincides with N. The Wright-Fisher model therefore lacks an important aspect of biological realism. Here, we present a method that allows Ne to be directly incorporated into the Wright-Fisher model. The modified model involves matrices whose size is determined by Ne. Thus apart from increased biological realism, the modified model also has reduced computational complexity, particularly so when Ne⪡N. For complex problems, it may be hard or impossible to numerically analyse the most commonly-used approximation of the Wright-Fisher model that incorporates Ne, namely the diffusion approximation. An alternative approach is simulation. However, the simulations need to be sufficiently detailed that they yield an effective size that is different to the census size. Simulations may also be time consuming and have attendant statistical errors. The method presented in this work may then be the only alternative to simulations, when Ne differs from N. We illustrate the straightforward application of the method to some problems involving allele fixation and the determination of the equilibrium site frequency spectrum. We then apply the method to the problem of fixation when three alleles are segregating in a population. This latter problem is significantly more complex than a two allele problem and since the diffusion equation cannot be numerically solved, the only other way Ne can be incorporated into the analysis is by simulation. We have achieved good accuracy in all cases considered. In summary, the present work extends the realism and tractability of an important model of evolutionary biology and population genetics. Copyright © 2016 Elsevier Ltd. All rights reserved.

SU-E-T-109: An Investigation of Including Variable Relative Biological Effectiveness in Intensity Modulated Proton Therapy Planning Optimization for Head and Neck Cancer Patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cao, W; Zaghian, M; Lim, G

2015-06-15

Purpose: The current practice of considering the relative biological effectiveness (RBE) of protons in intensity modulated proton therapy (IMPT) planning is to use a generic RBE value of 1.1. However, RBE is indeed a variable depending on the dose per fraction, the linear energy transfer, tissue parameters, etc. In this study, we investigate the impact of using variable RBE based optimization (vRBE-OPT) on IMPT dose distributions compared by conventional fixed RBE based optimization (fRBE-OPT). Methods: Proton plans of three head and neck cancer patients were included for our study. In order to calculate variable RBE, tissue specific parameters were obtainedmore » from the literature and dose averaged LET values were calculated by Monte Carlo simulations. Biological effects were calculated using the linear quadratic model and they were utilized in the variable RBE based optimization. We used a Polak-Ribiere conjugate gradient algorithm to solve the model. In fixed RBE based optimization, we used conventional physical dose optimization to optimize doses weighted by 1.1. IMPT plans for each patient were optimized by both methods (vRBE-OPT and fRBE-OPT). Both variable and fixed RBE weighted dose distributions were calculated for both methods and compared by dosimetric measures. Results: The variable RBE weighted dose distributions were more homogenous within the targets, compared with the fixed RBE weighted dose distributions for the plans created by vRBE-OPT. We observed that there were noticeable deviations between variable and fixed RBE weighted dose distributions if the plan were optimized by fRBE-OPT. For organs at risk sparing, dose distributions from both methods were comparable. Conclusion: Biological dose based optimization rather than conventional physical dose based optimization in IMPT planning may bring benefit in improved tumor control when evaluating biologically equivalent dose, without sacrificing OAR sparing, for head and neck cancer patients. The research is supported in part by National Institutes of Health Grant No. 2U19CA021239-35.« less

Evaluation of toxicity and estrogenicity of the landfill-concentrated leachate during advanced oxidation treatment: chemical analyses and bioanalytical tools.

PubMed

Wang, Guifang; Lu, Gang; Zhao, Jiandi; Yin, Pinghe; Zhao, Ling

2016-08-01

Landfill-concentrated leachate from membrane separation processes is a potential pollution source for the surroundings. In this study, the toxicity and estrogenicity potentials of concentrated leachate prior to and during UV-Fenton and Fenton treatments were assessed by a combination of chemical (di (2-ethylhexyl) phthalate and dibutyl phthalate were chosen as targets) and biological (Daphnia magna, Chlorella vulgaris, and E-screen assay) analyses. Removal efficiencies of measured di (2-ethylhexyl) phthalate and dibutyl phthalate were more than 97 % after treatment with the two methods. Biological tests showed acute toxicity effects on D. magna tests in untreated concentrated leachate samples, whereas acute toxicity on C. vulgaris tests was not observed. Both treatment methods were found to be efficient in reducing acute toxicity effects on D. magna tests. The E-screen test showed concentrated leachate had significant estrogenicity, UV-Fenton and Fenton treatment, especially the former, were effective methods for reducing estrogenicity of concentrated leachate. The EEQchem (estradiol equivalent concentration) of all samples could only explain 0.218-5.31 % range of the EEQbio. These results showed that UV-Fenton reagent could be considered as a suitable method for treatment of concentrated leachate, and the importance of the application of an integrated (biological + chemical) analytical approach for a comprehensive evaluation of treatment suitability.

Sphere of equivalence--a novel target volume concept for intraoperative radiotherapy using low-energy X rays.

PubMed

Herskind, Carsten; Griebel, Jürgen; Kraus-Tiefenbacher, Uta; Wenz, Frederik

2008-12-01

Accelerated partial breast radiotherapy with low-energy photons from a miniature X-ray machine is undergoing a randomized clinical trial (Targeted Intra-operative Radiation Therapy [TARGIT]) in a selected subgroup of patients treated with breast-conserving surgery. The steep radial dose gradient implies reduced tumor cell control with increasing depth in the tumor bed. The purpose was to compare the expected risk of local recurrence in this nonuniform radiation field with that after conventional external beam radiotherapy. The relative biologic effectiveness of low-energy photons was modeled using the linear-quadratic formalism including repair of sublethal lesions during protracted irradiation. Doses of 50-kV X-rays (Intrabeam) were converted to equivalent fractionated doses, EQD2, as function of depth in the tumor bed. The probability of local control was estimated using a logistic dose-response relationship fitted to clinical data from fractionated radiotherapy. The model calculations show that, for a cohort of patients, the increase in local control in the high-dose region near the applicator partly compensates the reduction of local control at greater distances. Thus a "sphere of equivalence" exists within which the risk of recurrence is equal to that after external fractionated radiotherapy. The spatial distribution of recurrences inside this sphere will be different from that after conventional radiotherapy. A novel target volume concept is presented here. The incidence of recurrences arising in the tumor bed around the excised tumor will test the validity of this concept and the efficacy of the treatment. Recurrences elsewhere will have implications for the rationale of TARGIT.

Responses to reductive stress in the cardiovascular system.

PubMed

Handy, Diane E; Loscalzo, Joseph

2017-08-01

There is a growing appreciation that reductive stress represents a disturbance in the redox state that is harmful to biological systems. On a cellular level, the presence of increased reducing equivalents and the lack of beneficial fluxes of reactive oxygen species can prevent growth factor-mediated signaling, promote mitochondrial dysfunction, increase apoptosis, and decrease cell survival. In this review, we highlight the importance of redox balance in maintaining cardiovascular homeostasis and consider the tenuous balance between oxidative and reductive stress. We explain the role of reductive stress in models of protein aggregation-induced cardiomyopathies, such as those caused by mutations in αB-crystallin. In addition, we discuss the role of NADPH oxidases in models of heart failure and ischemia-reperfusion to illustrate how oxidants may mediate the adaptive responses to injury. NADPH oxidase 4, a hydrogen peroxide generator, also has a major role in promoting vascular homeostasis through its regulation of vascular tone, angiogenic responses, and effects on atherogenesis. In contrast, the lack of antioxidant enzymes that reduce hydrogen peroxide, such as glutathione peroxidase 1, promotes vascular remodeling and is deleterious to endothelial function. Thus, we consider the role of oxidants as necessary signals to promote adaptive responses, such as the activation of Nrf2 and eNOS, and the stabilization of Hif1. In addition, we discuss the adaptive metabolic reprogramming in hypoxia that lead to a reductive state, and the subsequent cellular redistribution of reducing equivalents from NADH to other metabolites. Finally, we discuss the paradoxical ability of excess reducing equivalents to stimulate oxidative stress and promote injury. Copyright © 2017 Elsevier Inc. All rights reserved.

Systematic Review with Network Meta-Analysis: Comparative Efficacy of Biologics in the Treatment of Moderately to Severely Active Ulcerative Colitis

PubMed Central

Vickers, Adrian D.; Ainsworth, Claire; Mody, Reema; Bergman, Annika; Ling, Caroline S.; Medjedovic, Jasmina; Smyth, Michael

2016-01-01

Background Biological therapies are increasingly used to treat ulcerative colitis (UC). Aim To compare the efficacy of biologics in adults with moderately-to-severely active UC, stratified by prior exposure to anti-tumour necrosis factor (anti-TNF) therapy. Methods A systematic literature review was undertaken to identify studies of biologics approved for UC. Network meta-analysis was conducted for endpoints at induction and maintenance. Results Seven studies were included in the meta-analysis of induction treatment for anti-TNF therapy-naïve patients. All biologics were more effective than placebo in inducing clinical response, clinical remission, and mucosal healing. Infliximab demonstrated a statistically significant improvement over adalimumab in clinical response (odds ratio [OR] [95% credible interval (CrI)]: 2.19 [1.35–3.55]), clinical remission (OR [95% CrI]: 2.81 [1.49–5.49]), and mucosal healing (OR [95% CrI]: 2.23 [1.21–4.14]); there were no other significant differences between biologics for induction efficacy. Five studies were included in the meta-analysis of maintenance treatment, two studies rerandomised responder patients at end of induction, and three followed the same patients ‘straight through’. To account for design differences, the number of responders at end of induction was assumed to be equivalent to the number rerandomised. Vedolizumab showed significantly different durable clinical response from comparators (OR [95% CrI] infliximab 3.18 [1.14–9.20], golimumab 2.33 [1.04–5.41], and adalimumab 3.96 [1.67–9.84]). In anti-TNF therapy-experienced patients, only vedolizumab and adalimumab could be compared. At induction, no significant differences in efficacy were seen. During maintenance, vedolizumab showed significantly improved rates of mucosal healing versus adalimumab (OR [95% CrI]: 6.72 [1.36–41.0]). Conclusions This study expands the understanding of comparative efficacies of biologic treatments for UC, encompassing outcomes and populations not previously studied. All biologic treatments were effective for UC during induction. Vedolizumab demonstrated possible clinical benefits in the maintenance setting versus all comparators, irrespective of prior anti-TNF exposure and after adjusting for differences in study design. PMID:27776175

NUNDO: a numerical model of a human torso phantom and its application to effective dose equivalent calculations for astronauts at the ISS.

PubMed

Puchalska, Monika; Bilski, Pawel; Berger, Thomas; Hajek, Michael; Horwacik, Tomasz; Körner, Christine; Olko, Pawel; Shurshakov, Vyacheslav; Reitz, Günther

2014-11-01

The health effects of cosmic radiation on astronauts need to be precisely quantified and controlled. This task is important not only in perspective of the increasing human presence at the International Space Station (ISS), but also for the preparation of safe human missions beyond low earth orbit. From a radiation protection point of view, the baseline quantity for radiation risk assessment in space is the effective dose equivalent. The present work reports the first successful attempt of the experimental determination of the effective dose equivalent in space, both for extra-vehicular activity (EVA) and intra-vehicular activity (IVA). This was achieved using the anthropomorphic torso phantom RANDO(®) equipped with more than 6,000 passive thermoluminescent detectors and plastic nuclear track detectors, which have been exposed to cosmic radiation inside the European Space Agency MATROSHKA facility both outside and inside the ISS. In order to calculate the effective dose equivalent, a numerical model of the RANDO(®) phantom, based on computer tomography scans of the actual phantom, was developed. It was found that the effective dose equivalent rate during an EVA approaches 700 μSv/d, while during an IVA about 20 % lower values were observed. It is shown that the individual dose based on a personal dosimeter reading for an astronaut during IVA results in an overestimate of the effective dose equivalent of about 15 %, whereas under an EVA conditions the overestimate is more than 200 %. A personal dosemeter can therefore deliver quite good exposure records during IVA, but may overestimate the effective dose equivalent received during an EVA considerably.

Technical note: Equivalent genomic models with a residual polygenic effect.

PubMed

Liu, Z; Goddard, M E; Hayes, B J; Reinhardt, F; Reents, R

2016-03-01

Routine genomic evaluations in animal breeding are usually based on either a BLUP with genomic relationship matrix (GBLUP) or single nucleotide polymorphism (SNP) BLUP model. For a multi-step genomic evaluation, these 2 alternative genomic models were proven to give equivalent predictions for genomic reference animals. The model equivalence was verified also for young genotyped animals without phenotypes. Due to incomplete linkage disequilibrium of SNP markers to genes or causal mutations responsible for genetic inheritance of quantitative traits, SNP markers cannot explain all the genetic variance. A residual polygenic effect is normally fitted in the genomic model to account for the incomplete linkage disequilibrium. In this study, we start by showing the proof that the multi-step GBLUP and SNP BLUP models are equivalent for the reference animals, when they have a residual polygenic effect included. Second, the equivalence of both multi-step genomic models with a residual polygenic effect was also verified for young genotyped animals without phenotypes. Additionally, we derived formulas to convert genomic estimated breeding values of the GBLUP model to its components, direct genomic values and residual polygenic effect. Third, we made a proof that the equivalence of these 2 genomic models with a residual polygenic effect holds also for single-step genomic evaluation. Both the single-step GBLUP and SNP BLUP models lead to equal prediction for genotyped animals with phenotypes (e.g., reference animals), as well as for (young) genotyped animals without phenotypes. Finally, these 2 single-step genomic models with a residual polygenic effect were proven to be equivalent for estimation of SNP effects, too. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Effects of equivalence ratio variation on lean, stratified methane-air laminar counterflow flames

NASA Astrophysics Data System (ADS)

Richardson, E. S.; Granet, V. E.; Eyssartier, A.; Chen, J. H.

2010-11-01

The effects of equivalence ratio variations on flame structure and propagation have been studied computationally. Equivalence ratio stratification is a key technology for advanced low emission combustors. Laminar counterflow simulations of lean methane-air combustion have been presented which show the effect of strain variations on flames stabilized in an equivalence ratio gradient, and the response of flames propagating into a mixture with a time-varying equivalence ratio. 'Back supported' lean flames, whose products are closer to stoichiometry than their reactants, display increased propagation velocities and reduced thickness compared with flames where the reactants are richer than the products. The radical concentrations in the vicinity of the flame are modified by the effect of an equivalence ratio gradient on the temperature profile and thermal dissociation. Analysis of steady flames stabilized in an equivalence ratio gradient demonstrates that the radical flux through the flame, and the modified radical concentrations in the reaction zone, contribute to the modified propagation speed and thickness of stratified flames. The modified concentrations of radical species in stratified flames mean that, in general, the reaction rate is not accurately parametrized by progress variable and equivalence ratio alone. A definition of stratified flame propagation based upon the displacement speed of a mixture fraction dependent progress variable was seen to be suitable for stratified combustion. The response times of the reaction, diffusion, and cross-dissipation components which contribute to this displacement speed have been used to explain flame response to stratification and unsteady fluid dynamic strain.

Development of a bioanalytical test battery for water quality monitoring: Fingerprinting identified micropollutants and their contribution to effects in surface water.

PubMed

Neale, Peta A; Altenburger, Rolf; Aït-Aïssa, Selim; Brion, François; Busch, Wibke; de Aragão Umbuzeiro, Gisela; Denison, Michael S; Du Pasquier, David; Hilscherová, Klára; Hollert, Henner; Morales, Daniel A; Novák, Jiří; Schlichting, Rita; Seiler, Thomas-Benjamin; Serra, Helene; Shao, Ying; Tindall, Andrew J; Tollefsen, Knut Erik; Williams, Timothy D; Escher, Beate I

2017-10-15

Surface waters can contain a diverse range of organic pollutants, including pesticides, pharmaceuticals and industrial compounds. While bioassays have been used for water quality monitoring, there is limited knowledge regarding the effects of individual micropollutants and their relationship to the overall mixture effect in water samples. In this study, a battery of in vitro bioassays based on human and fish cell lines and whole organism assays using bacteria, algae, daphnids and fish embryos was assembled for use in water quality monitoring. The selection of bioassays was guided by the principles of adverse outcome pathways in order to cover relevant steps in toxicity pathways known to be triggered by environmental water samples. The effects of 34 water pollutants, which were selected based on hazard quotients, available environmental quality standards and mode of action information, were fingerprinted in the bioassay test battery. There was a relatively good agreement between the experimental results and available literature effect data. The majority of the chemicals were active in the assays indicative of apical effects, while fewer chemicals had a response in the specific reporter gene assays, but these effects were typically triggered at lower concentrations. The single chemical effect data were used to improve published mixture toxicity modeling of water samples from the Danube River. While there was a slight increase in the fraction of the bioanalytical equivalents explained for the Danube River samples, for some endpoints less than 1% of the observed effect could be explained by the studied chemicals. The new mixture models essentially confirmed previous findings from many studies monitoring water quality using both chemical analysis and bioanalytical tools. In short, our results indicate that many more chemicals contribute to the biological effect than those that are typically quantified by chemical monitoring programs or those regulated by environmental quality standards. This study not only demonstrates the utility of fingerprinting single chemicals for an improved understanding of the biological effect of pollutants, but also highlights the need to apply bioassays for water quality monitoring in order to prevent underestimation of the overall biological effect. Copyright © 2017 Elsevier Ltd. All rights reserved.

Introduction to the Canadian Scientific Advisory Committee on Respiratory and Allergy Therapies: in vivo evaluation for clinical testing in COPD and asthma therapy using generics.

PubMed

Mayers, Irvin

2012-08-01

Health Canada posted a guidance for in vivo testing of subsequent market entry (SME) inhaled corticosteroids (ICS) for treatment of asthma and published proceedings regarding SME products for chronic obstructive pulmonary disease (COPD). This manuscript reviews these recommendations and outlines their rationale. The Scientific Advisory Committee on Respiratory and Allergy Therapies (SAC-RAT) met between 2007 and 2009. The committee reviewed approval processes for SME ICS for asthma treatment and a draft guidance was posted by Health Canada. SAC-RAT also reviewed SME long-acting beta agonists (LABA) and fixed drug dose combinations (FDDC) for COPD treatment. SAC-RAT concluded that measuring airway eosinophils in mild, stable, steroid-naive, subjects was reproducible and measurable. Study duration could be reduced to only 3 weeks using this inflammatory outcome to establish therapeutic equivalence between SME ICS and Canadian reference product. A placebo limb of the trial was added to establish biological activity of the products. The committee recommended that LABA SME products be tested in a clinically stable, representative population with GOLD stage 2 and/or 3 COPD. There was not agreement regarding the extent of allowed FEV(1) reversibility in this population. The FEV(1) area under the curve (AUC) was recommended as a primary endpoint. For equivalence, both AUC and the shape of the curve (assessed by the peak and trough) over a 12-h period should be different from placebo but similar for the SME and reference products. Secondary endpoints were not recommended. Clinical presentations of asthma and COPD may overlap but prespecified disease phenotypes can separate the populations. ICS therapeutic equivalence can be assessed by reduction in eosinophil counts tested in steroid naive subjects. Increases in FEV(1) define LABA effects in moderate to severe COPD. When designing trials to assess therapeutic equivalence, the anticipated mechanism of action of the drug should be used to determine outcome measures.

A new model for biological effects of radiation and the driven force of molecular evolution

NASA Astrophysics Data System (ADS)

Wada, Takahiro; Manabe, Yuichiro; Nakajima, Hiroo; Tsunoyama, Yuichi; Bando, Masako

We proposed a new mathematical model to estimate biological effects of radiation, which we call Whack-A-Mole (WAM) model. A special feature of WAM model is that it involves the dose rate of radiation as a key ingredient. We succeeded to reproduce the experimental data of various species concerning the radiation induced mutation frequencies. From the analysis of the mega-mouse experiments, we obtained the mutation rate per base-pair per year for mice which is consistent with the so-called molecular clock in evolution genetics, 10-9 mutation/base-pair/year. Another important quantity is the equivalent dose rate for the whole spontaneous mutation, deff. The value of deff for mice is 1.1*10-3 Gy/hour which is much larger than the dose rate of natural radiation (10- (6 - 7) Gy/hour) by several orders of magnitude. We also analyzed Drosophila data and obtained essentially the same numbers. This clearly indicates that the natural radiation is not the dominant driving force of the molecular evolution, but we should look for other factors, such as miscopy of DNA in duplication process. We believe this is the first quantitative proof of the small contribution of the natural radiation in the molecular evolution.

Identification of mammalian cell genotoxins in respirable diesel exhaust particles by bioassay-directed chemical analysis.

PubMed

Oh, Seung-Min; Chung, Kyu-Hyuck

2006-03-01

A bioassay-directed chemical analysis which consists of mammalian cell bioassays (comet assay, CBMN assay and EROD-microbioassay) in conjunction with analytical measurements was performed to identify the most biologically active compounds of the diesel exhaust particulate matters (DEPs) on mutagenic activity. These bioassay systems were suitable to estimate the mammalian genotoxic potentials of pollutants present in low concentrations in limited environmental samples, as is the case with DEPEs. The results from mutagenic assay showed that the aromatic and slightly polar fraction of DEPs induced chromosomal damage and DNA breakage in a non-cytotoxic dose. It was also revealed that indirect-acting mutagens may mainly contribute to the mutagenic effect of aromatic fraction via the enzyme metabolism system. In the aromatic fraction, several indirect-acting mutagenic PAHs such as dibenzo(a,h)anthracene, chrysene, and 1,2-benzanthracene were detected by GC-MS and the complex mixture effect of this fraction was quantified in terms of its biological-TCDD equivalent concentration (bio-TEQ) which was 32.82 bio-TEQ ng/g-DEPs by EROD-microbioassay. Conclusively, we confirmed that indirect-acting mutagens contained in aromatic fraction may be important causatives of the genotoxicity of extracts of DEPs by integrating the results obtained from a mammalian cell bioassay-directed fractionation.

Evaluation of DNA damage induced by Auger electrons from 137Cs.

PubMed

Watanabe, Ritsuko; Hattori, Yuya; Kai, Takeshi

2016-11-01

To understand the biological effect of external and internal exposure from 137 Cs, DNA damage spectrum induced by directly emitted electrons (γ-rays, internal conversion electrons, Auger electrons) from 137 Cs was compared with that induced by 137 Cs γ-rays. Monte Carlo track simulation method was used to calculate the microscopic energy deposition pattern in liquid water. Simulation was performed for the two simple target systems in microscale. Radiation sources were placed inside for one system and outside for another system. To simulate the energy deposition by directly emitted electrons from 137 Cs placed inside the system, the multiple ejections of electrons after internal conversion were considered. In the target systems, induction process of DNA damage was modeled and simulated for both direct energy deposition and the water radical reaction on the DNA. The yield and spatial distribution of simple and complex DNA damage including strand breaks and base lesions were calculated for irradiation by electrons and γ-rays from 137 Cs. The simulation showed that the significant difference in DNA damage spectrum was not caused by directly ejected electrons and γ-rays from 137 Cs. The result supports the existing perception that the biological effects by internal and external exposure by 137 Cs are equivalent.

40 CFR 721.8450 - 2-Propenoic acid, 2-methyl-, 2-[3-(2H-benzotriazol-2-yl)-4-hydroxyphenyl]ethyl ester.

Code of Federal Regulations, 2010 CFR

2010-07-01

..., and consumer activities. Requirements as specified in § 721.80 (l) and (q). (iv) Release to water...)(4), if the waste stream containing the PMN substance will be treated using biological treatment (activated sludge or equivalent) plus clarification, then the amount of PMN substance reasonably likely to be...

One-dimensional nonlinear elastodynamic models and their local conservation laws with applications to biological membranes.

PubMed

Cheviakov, A F; Ganghoffer, J-F

2016-05-01

The framework of incompressible nonlinear hyperelasticity and viscoelasticity is applied to the derivation of one-dimensional models of nonlinear wave propagation in fiber-reinforced elastic solids. Equivalence transformations are used to simplify the resulting wave equations and to reduce the number of parameters. Local conservation laws and global conserved quantities of the models are systematically computed and discussed, along with other related mathematical properties. Sample numerical solutions are presented. The models considered in the paper are appropriate for the mathematical description of certain aspects of the behavior of biological membranes and similar structures. Copyright © 2015 Elsevier Ltd. All rights reserved.

Postdoctoral Fellow | Center for Cancer Research

Cancer.gov

A post-doctoral fellowship is currently available for productive, highly-motivated, and energetic individuals in the Inflammation and Tumorigenesis Section of Dr. Yinling Hu at the NCI-Frederick campus.  A dynamic research environment and outstanding resources are available for enthusiastic individuals.  Requirements include a Ph.D., M.D., or equivalent degree and experience in Immunology, Molecular Biology, and/or Signaling Research. Candidate must have excellent verbal, written communication and organizational skills, and the ability to handle multiple projects simultaneously. The project will be to investigate mechanisms of IKK/NF-kB-involved lung and skin carcinogenesis/cancer biology, tumor initiating cells, and therapy by using mouse genetic modified mouse models.

Equivalent-Continuum Modeling With Application to Carbon Nanotubes

NASA Technical Reports Server (NTRS)

Odegard, Gregory M.; Gates, Thomas S.; Nicholson, Lee M.; Wise, Kristopher E.

2002-01-01

A method has been proposed for developing structure-property relationships of nano-structured materials. This method serves as a link between computational chemistry and solid mechanics by substituting discrete molecular structures with equivalent-continuum models. It has been shown that this substitution may be accomplished by equating the vibrational potential energy of a nano-structured material with the strain energy of representative truss and continuum models. As important examples with direct application to the development and characterization of single-walled carbon nanotubes and the design of nanotube-based devices, the modeling technique has been applied to determine the effective-continuum geometry and bending rigidity of a graphene sheet. A representative volume element of the chemical structure of graphene has been substituted with equivalent-truss and equivalent continuum models. As a result, an effective thickness of the continuum model has been determined. This effective thickness has been shown to be significantly larger than the interatomic spacing of graphite. The effective thickness has been shown to be significantly larger than the inter-planar spacing of graphite. The effective bending rigidity of the equivalent-continuum model of a graphene sheet was determined by equating the vibrational potential energy of the molecular model of a graphene sheet subjected to cylindrical bending with the strain energy of an equivalent continuum plate subjected to cylindrical bending.

Positive effects of vegetation: urban heat island and green roofs.

PubMed

Susca, T; Gaffin, S R; Dell'osso, G R

2011-01-01

This paper attempts to evaluate the positive effects of vegetation with a multi-scale approach: an urban and a building scale. Monitoring the urban heat island in four areas of New York City, we have found an average of 2 °C difference of temperatures between the most and the least vegetated areas, ascribable to the substitution of vegetation with man-made building materials. At micro-scale, we have assessed the effect of surface albedo on climate through the use of a climatological model. Then, using the CO(2) equivalents as indicators of the impact on climate, we have compared the surface albedo, and the construction, replacement and use phase of a black, a white and a green roof. By our analyses, we found that both the white and the green roofs are less impactive than the black one; with the thermal resistance, the biological activity of plants and the surface albedo playing a crucial role. Copyright © 2011 Elsevier Ltd. All rights reserved.

Purification and biological characterization of soluble, recombinant mouse IFNβ expressed in insect cells.

PubMed

Stifter, Sebastian A; Gould, Jodee A; Mangan, Niamh E; Reid, Hugh H; Rossjohn, Jamie; Hertzog, Paul J; de Weerd, Nicole A

2014-02-01

Interferon β (IFNβ) is a member of the type I interferon family of cytokines widely recognised for their anti-viral, anti-proliferative and immunomodulatory properties. Recombinant, biologically active forms of this cytokine are used clinically for the treatment of multiple sclerosis and in laboratories to study the role of this cytokine in health and disease. Established methods for expression of IFNβ utilise either bacterial systems from which the insoluble recombinant proteins must be refolded, or mammalian expression systems in which large volumes of cell culture are required for recovery of acceptable yields. Utilising the baculovirus expression system and Trichoplusia ni (Cabbage Looper) BTI-TN-5B1-4 cell line, we report a reproducible method for production and purification of milligram/litre quantities of biologically active murine IFNβ. Due to the design of our construct and the eukaryotic nature of insect cells, the resulting soluble protein is secreted allowing purification of the Histidine-tagged natively-folded protein from the culture supernatant. The IFNβ purification method described is a two-step process employing immobilised metal-ion affinity chromatography (IMAC) and reverse-phase high performance liquid chromatography (RP-HPLC) that results in production of significantly more purified IFNβ than any other reported eukaryotic-based expression system. Recombinant murine IFNβ produced by this method was natively folded and demonstrated hallmark type I interferon biological effects including antiviral and anti-proliferative activities, and induced genes characteristic of IFNβ activity in vivo. Recombinant IFNβ also had specific activity levels exceeding that of the commercially available equivalent. Together, our findings provide a method for production of highly pure, biologically active murine IFNβ. Copyright © 2013 Elsevier Inc. All rights reserved.

Ionizing radiation induced cataracts: Recent biological and mechanistic developments and perspectives for future research.

PubMed

Ainsbury, Elizabeth A; Barnard, Stephen; Bright, Scott; Dalke, Claudia; Jarrin, Miguel; Kunze, Sarah; Tanner, Rick; Dynlacht, Joseph R; Quinlan, Roy A; Graw, Jochen; Kadhim, Munira; Hamada, Nobuyuki

The lens of the eye has long been considered as a radiosensitive tissue, but recent research has suggested that the radiosensitivity is even greater than previously thought. The 2012 recommendation of the International Commission on Radiological Protection (ICRP) to substantially reduce the annual occupational equivalent dose limit for the ocular lens has now been adopted in the European Union and is under consideration around the rest of the world. However, ICRP clearly states that the recommendations are chiefly based on epidemiological evidence because there are a very small number of studies that provide explicit biological, mechanistic evidence at doses <2Gy. This paper aims to present a review of recently published information on the biological and mechanistic aspects of cataracts induced by exposure to ionizing radiation (IR). The data were compiled by assessing the pertinent literature in several distinct areas which contribute to the understanding of IR induced cataracts, information regarding lens biology and general processes of cataractogenesis. Results from cellular and tissue level studies and animal models, and relevant human studies, were examined. The main focus was the biological effects of low linear energy transfer IR, but dosimetry issues and a number of other confounding factors were also considered. The results of this review clearly highlight a number of gaps in current knowledge. Overall, while there have been a number of recent advances in understanding, it remains unknown exactly how IR exposure contributes to opacification. A fuller understanding of how exposure to relatively low doses of IR promotes induction and/or progression of IR-induced cataracts will have important implications for prevention and treatment of this disease, as well as for the field of radiation protection. Crown Copyright © 2016. Published by Elsevier B.V. All rights reserved.

Contribution of Priority PAHs and POPs to Ah Receptor-Mediated Activities in Sediment Samples from the River Elbe Estuary, Germany

PubMed Central

Otte, Jens C.; Keiter, Steffen; Faßbender, Christopher; Higley, Eric B.; Rocha, Paula Suares; Brinkmann, Markus; Wahrendorf, Dierk-Steffen; Manz, Werner; Wetzel, Markus A.; Braunbeck, Thomas; Giesy, John P.; Hecker, Markus; Hollert, Henner

2013-01-01

The estuary of the River Elbe between Hamburg and the North Sea (Germany) is a sink for contaminated sediment and suspended particulate matter (SPM). One major concern is the effect of human activities on the hydrodynamics, particularly the intensive dredging activities in this area that may result in remobilization of sediment-bound pollutants. The aim of this study was to identify pollutants contributing to the toxicological risk associated with re-suspension of sediments in the Elbe Estuary by use of an effect-directed analysis that combines chemical and biological analyses in with specific fractionation techniques. Sediments were collected from sites along the Elbe Estuary and a site from a small harbor basin of the Elbe Estuary that is known to be polluted. The sixteen priority EPA-PAHs were quantified in organic extracts of sediments. In addition, dioxin equivalents of sediments were investigated by use of the 7-ethoxyresorufin O-deethylase assay with RTL-W1 cells and the Ah receptor-mediated luciferase transactivation assay with H4IIE-luc cells. Quantification of the 16 priority PAHs revealed that sediments were moderately contaminated at all of the sites in the Elbe River Estuary (<0.02–0.906 µg/g dw). Sediments contained relatively small concentrations of dioxin equivalents (Bio-TEQ) with concentrations ranging from 15.5 to 322 pg/g dw, which were significantly correlated with dioxin equivalents calculated based on toxicity reference values and concentrations of PAH. The concentration of Bio-TEQ at the reference site exceeded 200,000 pg/g dw. In a potency balance the 16 PAHs explained between 47 and 118% of the Bio-TEQ in the luciferase assay, which can be explained by the constant input of PAHs bound to SPM from the upper course of the Elbe River into its estuary. Successful identification of a significant portion of dioxin-like activity to priority PAHs in complex environmental samples such as sediments has rarely been reported. PMID:24146763

Persistent activation of DNA damage signaling in response to complex mixtures of PAHs in air particulate matter

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jarvis, Ian W.H., E-mail: Ian.Jarvis@ki.se; Bergvall, Christoffer, E-mail: Christoffer.Bergvall@anchem.su.se; Bottai, Matteo, E-mail: Matteo.Bottai@ki.se

2013-02-01

Complex mixtures of polycyclic aromatic hydrocarbons (PAHs) are present in air particulate matter (PM) and have been associated with many adverse human health effects including cancer and respiratory disease. However, due to their complexity, the risk of exposure to mixtures is difficult to estimate. In the present study the effects of binary mixtures of benzo[a]pyrene (BP) and dibenzo[a,l]pyrene (DBP) and complex mixtures of PAHs in urban air PM extracts on DNA damage signaling was investigated. Applying a statistical model to the data we observed a more than additive response for binary mixtures of BP and DBP on activation of DNAmore » damage signaling. Persistent activation of checkpoint kinase 1 (Chk1) was observed at significantly lower BP equivalent concentrations in air PM extracts than BP alone. Activation of DNA damage signaling was also more persistent in air PM fractions containing PAHs with more than four aromatic rings suggesting larger PAHs contribute a greater risk to human health. Altogether our data suggests that human health risk assessment based on additivity such as toxicity equivalency factor scales may significantly underestimate the risk of exposure to complex mixtures of PAHs. The data confirms our previous findings with PAH-contaminated soil (Niziolek-Kierecka et al., 2012) and suggests a possible role for Chk1 Ser317 phosphorylation as a biological marker for future analyses of complex mixtures of PAHs. -- Highlights: ► Benzo[a]pyrene (BP), dibenzo[a,l]pyrene (DBP) and air PM PAH extracts were compared. ► Binary mixture of BP and DBP induced a more than additive DNA damage response. ► Air PM PAH extracts were more potent than toxicity equivalency factor estimates. ► Larger PAHs (> 4 rings) contribute more to the genotoxicity of PAHs in air PM. ► Chk1 is a sensitive marker for persistent activation of DNA damage signaling from PAH mixtures.« less

Observability of Boolean multiplex control networks

NASA Astrophysics Data System (ADS)

Wu, Yuhu; Xu, Jingxue; Sun, Xi-Ming; Wang, Wei

2017-04-01

Boolean multiplex (multilevel) networks (BMNs) are currently receiving considerable attention as theoretical arguments for modeling of biological systems and system level analysis. Studying control-related problems in BMNs may not only provide new views into the intrinsic control in complex biological systems, but also enable us to develop a method for manipulating biological systems using exogenous inputs. In this article, the observability of the Boolean multiplex control networks (BMCNs) are studied. First, the dynamical model and structure of BMCNs with control inputs and outputs are constructed. By using of Semi-Tensor Product (STP) approach, the logical dynamics of BMCNs is converted into an equivalent algebraic representation. Then, the observability of the BMCNs with two different kinds of control inputs is investigated by giving necessary and sufficient conditions. Finally, examples are given to illustrate the efficiency of the obtained theoretical results.

Analysis of radiation risk from alpha particle component of solar particle events

NASA Technical Reports Server (NTRS)

Cucinotta, F. A.; Townsend, L. W.; Wilson, J. W.; Golightly, M. J.; Weyland, M.

1994-01-01

The solar particle events (SPE) will contain a primary alpha particle component, representing a possible increase in the potential risk to astronauts during an SPE over the often studied proton component. We discuss the physical interactions of alpha particles important in describing the transport of these particles through spacecraft and body shielding. Models of light ion reactions are presented and their effects on energy and linear energy transfer (LET) spectra in shielding discussed. We present predictions of particle spectra, dose, and dose equivalent in organs of interest for SPE spectra typical of those occurring in recent solar cycles. The large events of solar cycle 19 are found to have substantial increase in biological risk from alpha particles, including a large increase in secondary neutron production from alpha particle breakup.

Biological competition: Decision rules, pattern formation, and oscillations

PubMed Central

Grossberg, Stephen

1980-01-01

Competition solves a universal problem about pattern processing by cellular systems. Competition allows cells to automatically retune their sensitivity to avoid noise and saturation effects. All competitive systems induce decision schemes that permit them to be classified. Systems are identified that achieve global pattern formation, or decision-making, no matter how their parameters are chosen. Oscillations can occur due to contradictions in a system's decision scheme. The pattern formation and oscillation results are extreme examples of a complementarity principle that seems to hold for competitive systems. Nonlinear competitive systems can sometimes appear, to a macroscopic observer, to have linear and cooperative properties, although the two types of systems are not equivalent. This observation is relevant to theories about the evolutionary transition from competitive to cooperative behavior. PMID:16592807

Precision Tests of a Quantum Hall Effect Device DC Equivalent Circuit Using Double-Series and Triple-Series Connections

PubMed Central

Jeffery, A.; Elmquist, R. E.; Cage, M. E.

1995-01-01

Precision tests verify the dc equivalent circuit used by Ricketts and Kemeny to describe a quantum Hall effect device in terms of electrical circuit elements. The tests employ the use of cryogenic current comparators and the double-series and triple-series connection techniques of Delahaye. Verification of the dc equivalent circuit in double-series and triple-series connections is a necessary step in developing the ac quantum Hall effect as an intrinsic standard of resistance. PMID:29151768

Effects of strength vs aerobic exercise on pain severity in adults with fibromyalgia: a randomized equivalence trial.

PubMed

Hooten, W Michael; Qu, Wenchun; Townsend, Cynthia O; Judd, Jeffrey W

2012-04-01

Strength training and aerobic exercise have beneficial effects on pain in adults with fibromyalgia. However, the equivalence of strengthening and aerobic exercise has not been reported. The primary aim of this randomized equivalence trial involving patients with fibromyalgia admitted to an interdisciplinary pain treatment program was to test the hypothesis that strengthening (n=36) and aerobic (n=36) exercise have equivalent effects (95% confidence interval within an equivalence margin ± 8) on pain, as measured by the pain severity subscale of the Multidimensional Pain Inventory. Secondary aims included determining the effects of strengthening and aerobic exercise on peak Vo(2) uptake, leg strength, and pressure pain thresholds. In an intent-to-treat analysis, the mean (± standard deviation) pain severity scores for the strength and aerobic groups at study completion were 34.4 ± 11.5 and 37.6 ± 11.9, respectively. The group difference was -3.2 (95% confidence interval, -8.7 to 2.3), which was within the equivalence margin of Δ8. Significant improvements in pain severity (P<.001), peak Vo(2) (P<.001), strength (P<.001), and pain thresholds (P<.001) were observed from baseline to week 3 in the intent-to-treat analysis; however, patients in the aerobic group (mean change 2.0 ± 2.6 mL/kg/min) experienced greater gains (P<.013) in peak Vo(2) compared to the strength group (mean change 0.4 ± 2.6 mL/kg/min). Knowledge of the equivalence and physiological effects of exercise have important clinical implications that could allow practitioners to target exercise recommendations on the basis of comorbid medical conditions or patient preference for a particular type of exercise. This study found that strength and aerobic exercise had equivalent effects on reducing pain severity among patients with fibromyalgia. Copyright © 2012 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Compact Tissue-equivalent Proportional Counter for Deep Space Human Missions.

PubMed

Straume, T; Braby, L A; Borak, T B; Lusby, T; Warner, D W; Perez-Nunez, D

2015-10-01

Effects on human health from the complex radiation environment in deep space have not been measured and can only be simulated here on Earth using experimental systems and beams of radiations produced by accelerators, usually one beam at a time. This makes it particularly important to develop instruments that can be used on deep-space missions to measure quantities that are known to be relatable to the biological effectiveness of space radiation. Tissue-equivalent proportional counters (TEPCs) are such instruments. Unfortunately, present TEPCs are too large and power intensive to be used beyond low Earth orbit (LEO). Here, the authors describe a prototype of a compact TEPC designed for deep space applications with the capability to detect both ambient galactic cosmic rays and intense solar particle event radiation. The device employs an approach that permits real-time determination of yD (and thus quality factor) using a single detector. This was accomplished by assigning sequential sampling intervals as detectors “1” and “2” and requiring the intervals to be brief compared to the change in dose rate. Tests with g rays show that the prototype instrument maintains linear response over the wide dose-rate range expected in space with an accuracy of better than 5% for dose rates above 3 mGy h(-1). Measurements of yD for 200 MeV n(-1) carbon ions were better than 10%. Limited tests with fission spectrum neutrons show absorbed dose-rate accuracy better than 15%.

Compact Tissue-equivalent Proportional Counter for Deep Space Human Missions

PubMed Central

Straume, T.; Braby, L.A.; Borak, T.B.; Lusby, T.; Warner, D.W.; Perez-Nunez, D.

2015-01-01

Abstract Effects on human health from the complex radiation environment in deep space have not been measured and can only be simulated here on Earth using experimental systems and beams of radiations produced by accelerators, usually one beam at a time. This makes it particularly important to develop instruments that can be used on deep-space missions to measure quantities that are known to be relatable to the biological effectiveness of space radiation. Tissue-equivalent proportional counters (TEPCs) are such instruments. Unfortunately, present TEPCs are too large and power intensive to be used beyond low Earth orbit (LEO). Here, the authors describe a prototype of a compact TEPC designed for deep space applications with the capability to detect both ambient galactic cosmic rays and intense solar particle event radiation. The device employs an approach that permits real-time determination of (and thus quality factor) using a single detector. This was accomplished by assigning sequential sampling intervals as detectors “1” and “2” and requiring the intervals to be brief compared to the change in dose rate. Tests with γ rays show that the prototype instrument maintains linear response over the wide dose-rate range expected in space with an accuracy of better than 5% for dose rates above 3 mGy h−1. Measurements of for 200 MeV n−1 carbon ions were better than 10%. Limited tests with fission spectrum neutrons show absorbed dose-rate accuracy better than 15%. PMID:26313585

Exploring the folkbiological conception of human nature

PubMed Central

Linquist, Stefan; Machery, Edouard; Griffiths, Paul E.; Stotz, Karola

2011-01-01

Integrating the study of human diversity into the human evolutionary sciences requires substantial revision of traditional conceptions of a shared human nature. This process may be made more difficult by entrenched, ‘folkbiological’ modes of thought. Earlier work by the authors suggests that biologically naive subjects hold an implicit theory according to which some traits are expressions of an animal's inner nature while others are imposed by its environment. In this paper, we report further studies that extend and refine our account of this aspect of folkbiology. We examine biologically naive subjects' judgments about whether traits of an animal are ‘innate’, ‘in its DNA’ or ‘part of its nature’. Subjects do not understand these three descriptions to be equivalent. Both innate and in its DNA have the connotation that the trait is species-typical. This poses an obstacle to the assimilation of the biology of polymorphic and plastic traits by biologically naive audiences. Researchers themselves may not be immune to the continuing pull of folkbiological modes of thought. PMID:21199848

Seasonal copepod lipid pump promotes carbon sequestration in the deep North Atlantic

PubMed Central

Jónasdóttir, Sigrún Huld; Visser, André W.; Richardson, Katherine; Heath, Michael R.

2015-01-01

Estimates of carbon flux to the deep oceans are essential for our understanding of global carbon budgets. Sinking of detrital material (“biological pump”) is usually thought to be the main biological component of this flux. Here, we identify an additional biological mechanism, the seasonal “lipid pump,” which is highly efficient at sequestering carbon into the deep ocean. It involves the vertical transport and metabolism of carbon rich lipids by overwintering zooplankton. We show that one species, the copepod Calanus finmarchicus overwintering in the North Atlantic, sequesters an amount of carbon equivalent to the sinking flux of detrital material. The efficiency of the lipid pump derives from a near-complete decoupling between nutrient and carbon cycling—a “lipid shunt,” and its direct transport of carbon through the mesopelagic zone to below the permanent thermocline with very little attenuation. Inclusion of the lipid pump almost doubles the previous estimates of deep-ocean carbon sequestration by biological processes in the North Atlantic. PMID:26338976

Biological and Economic Productivity of Mixed-Aged Loblolly Pine Stands in the South

Treesearch

Ronald Raunikar; Joseph Buongiorno; Jeffrey P. Prestemon; Karen Lee-Abt

1999-01-01

The financial performance of the 991 sample plots of uneven-aged loblolly-hardwood stands in the Central South FIA database examined in this report depend crucially on real price trends. Equivalent annual income (EAI) is the measure of economic performance. The regional market stumpage price data are from the Timber Mart-South database. For this set of prices, a...

Combined Administration of Recombinant Human Megakaryocyte Growth and Development Factor and Granulocyte Colony-Stimulating Factor Enhances Multilineage Hematopoietic Reconstitution in Nonhuman Primates after Radiation-Induced Marrow Aplasia

DTIC Science & Technology

1996-05-01

dose would yield an equivalent or better biological activity. Neupogen ® ( Filgrastim ), r-metHuG-CSF, was produced in E. coli as a...recombinant human granulocyte colony-stimulating factor on hematopoiesis of normal dogs and on hematopoi- etic recovery after otherwise lethal total body

Russian Olive Biology, Invasion, and Ecological Impacts in Western North America

DTIC Science & Technology

2016-07-01

habitat for bird species , but is not functionally equivalent to native vegetation. Leatherman (2011) lists a variety of birds that consume fruits, sap...abundance, but intermediate avian species richness and diversity, in Russian olive stands. Russian olive bird communities were somewhat similar to...provided distinctive habitat for some bird species (e.g., least flycatchers [Empidonax minimus], red-eyed vireos [Vireo olivaceous]), while providing

Investigating Coccolithophorid Biology in the Sedimentary Laboratory

NASA Astrophysics Data System (ADS)

McClelland, H. L. O.; Barbarin, N.; Beaufort, L.; Hermoso, M.; Rickaby, R. E. M.

2014-12-01

Coccolithophores are the ocean's dominant calcifying phytoplankton; they play an important, but poorly understood, role in long-term biogeochemical climatic feedbacks. Calcite producing marine organisms are likely to calcify less in a future world where higher carbon dioxide concentrations will lead to ocean acidification (OA), but coccolithophores may be the exception. In coccolithophores calcification occurs in an intracellular vesicle, where the site of calcite precipitation is buffered from the external environment and is subject to a uniquely high degree of biological control. Culture manipulation experiments mimicking the effects of OA in the laboratory have yielded empirical evidence for phenotypic plasticity, competition and evolutionary adaptation in asexual populations. However, the extent to which these results are representative of natural populations, and of the response over timescales of greater than a few hundred generations, is unclear. Here we describe a new sediment-based proxy for the PIC:POC (particulate inorganic to particulate organic carbon ratio) of coccolithophore biomass, which is equivalent to the fractional energy contribution to calcification at constant pH, and a biologically meaningful measure of the organism's tendency to calcify. Employing the geological record as a laboratory, we apply this proxy to sedimentary material from the southern Pacific Ocean to investigate the integrated response of real ancient coccolithophore populations to environmental change over many thousands of years. Our results provide a new perspective on phenotypic change in real populations of coccolithophorid algae over long timescales.

Risk-adaptive radiotherapy

NASA Astrophysics Data System (ADS)

Kim, Yusung

Currently, there is great interest in integrating biological information into intensity-modulated radiotherapy (IMRT) treatment planning with the aim of boosting high-risk tumor subvolumes. Selective boosting of tumor subvolumes can be accomplished without violating normal tissue complication constraints using information from functional imaging. In this work we have developed a risk-adaptive optimization-framework that utilizes a nonlinear biological objective function. Employing risk-adaptive radiotherapy for prostate cancer, it is possible to increase the equivalent uniform dose (EUD) by up to 35.4 Gy in tumor subvolumes having the highest risk classification without increasing normal tissue complications. Subsequently, we have studied the impact of functional imaging accuracy, and found on the one hand that loss in sensitivity had a large impact on expected local tumor control, which was maximal when a low-risk classification for the remaining low risk PTV was chosen. While on the other hand loss in specificity appeared to have a minimal impact on normal tissue sparing. Therefore, it appears that in order to improve the therapeutic ratio a functional imaging technique with a high sensitivity, rather than specificity, is needed. Last but not least a comparison study between selective boosting IMRT strategies and uniform-boosting IMRT strategies yielding the same EUD to the overall PTV was carried out, and found that selective boosting IMRT considerably improves expected TCP compared to uniform-boosting IMRT, especially when lack of control of the high-risk tumor subvolumes is the cause of expected therapy failure. Furthermore, while selective boosting IMRT, using physical dose-volume objectives, did yield similar rectal and bladder sparing when compared its equivalent uniform-boosting IMRT plan, risk-adaptive radiotherapy, utilizing biological objective functions, did yield a 5.3% reduction in NTCP for the rectum. Hence, in risk-adaptive radiotherapy the therapeutic ratio can be increased over that which can be achieved with conventional selective boosting IMRT using physical dose-volume objectives. In conclusion, a novel risk-adaptive radiotherapy strategy is proposed and promises increased expected local control for locoregionally advanced tumors with equivalent or better normal tissue sparing.

Creating beauty: creativity compensates for low physical attractiveness when individuals assess the attractiveness of social and romantic partners.

PubMed

Watkins, Christopher D

2017-04-01

Although creativity is attractive in a potential mate, it is unclear (i) whether the effects of creativity on attractiveness generalize to other social contexts and (ii) whether creativity has equivalent effects on men's and women's attractiveness. As social knowledge of creativity may either enhance or 'offset' the appeal of social partners who differ in physical attractiveness, three repeated measures experiments were conducted to directly address these issues. Here, participants rated a series of face-text pairs for attractiveness on trials that differed in one of four combinations of facial attractiveness (attractive and less attractive) and creativity (creative and less creative), rating story-tellers in two experiments (short interpretations of an identical painting) and creative ideas in a further experiment (alternative uses for an everyday object). Regardless of the sex of the judge, creativity and facial attractiveness had independent effects on men's overall attractiveness (initial experiment) and, in further experiments, more substantial effects on the attractiveness of men with less attractive faces than men with attractive faces (when using a different measure of creativity) and specific effects on the attractiveness of individuals with less attractive faces (when using different face stimuli). Collectively, across three experiments, these findings suggest that creativity may compensate for putative cues to lower biological 'quality' and that the benefits of creativity to social groups more generally enhance attraction to creative men (in two experiments) and creative men and women (one experiment). More broadly, the data suggest that species can integrate knowledge of cognitive intelligence with visual cues to biological 'quality' to facilitate mate and/or ally choice.

Network cosmology.

PubMed

Krioukov, Dmitri; Kitsak, Maksim; Sinkovits, Robert S; Rideout, David; Meyer, David; Boguñá, Marián

2012-01-01

Prediction and control of the dynamics of complex networks is a central problem in network science. Structural and dynamical similarities of different real networks suggest that some universal laws might accurately describe the dynamics of these networks, albeit the nature and common origin of such laws remain elusive. Here we show that the causal network representing the large-scale structure of spacetime in our accelerating universe is a power-law graph with strong clustering, similar to many complex networks such as the Internet, social, or biological networks. We prove that this structural similarity is a consequence of the asymptotic equivalence between the large-scale growth dynamics of complex networks and causal networks. This equivalence suggests that unexpectedly similar laws govern the dynamics of complex networks and spacetime in the universe, with implications to network science and cosmology.

Network Cosmology

PubMed Central

Krioukov, Dmitri; Kitsak, Maksim; Sinkovits, Robert S.; Rideout, David; Meyer, David; Boguñá, Marián

2012-01-01

Prediction and control of the dynamics of complex networks is a central problem in network science. Structural and dynamical similarities of different real networks suggest that some universal laws might accurately describe the dynamics of these networks, albeit the nature and common origin of such laws remain elusive. Here we show that the causal network representing the large-scale structure of spacetime in our accelerating universe is a power-law graph with strong clustering, similar to many complex networks such as the Internet, social, or biological networks. We prove that this structural similarity is a consequence of the asymptotic equivalence between the large-scale growth dynamics of complex networks and causal networks. This equivalence suggests that unexpectedly similar laws govern the dynamics of complex networks and spacetime in the universe, with implications to network science and cosmology. PMID:23162688

Characterization of the radiation environment at the UNLV accelerator facility during operation of the Varian M6 linac

NASA Astrophysics Data System (ADS)

Hodges, M.; Barzilov, A.; Chen, Y.; Lowe, D.

2016-10-01

The bremsstrahlung photon flux from the UNLV particle accelerator (Varian M6 model) was determined using MCNP5 code for 3 MeV and 6 MeV incident electrons. Human biological equivalent dose rates due to accelerator operation were evaluated using the photon flux with the flux-to-dose conversion factors. Dose rates were computed for the accelerator facility for M6 linac use under different operating conditions. The results showed that the use of collimators and linac internal shielding significantly reduced the dose rates throughout the facility. It was shown that the walls of the facility, in addition to the earthen berm enveloping the building, provide equivalent shielding to reduce dose rates outside to below the 2 mrem/h limit.

Bond Graph Modeling of Chemiosmotic Biomolecular Energy Transduction.

PubMed

Gawthrop, Peter J

2017-04-01

Engineering systems modeling and analysis based on the bond graph approach has been applied to biomolecular systems. In this context, the notion of a Faraday-equivalent chemical potential is introduced which allows chemical potential to be expressed in an analogous manner to electrical volts thus allowing engineering intuition to be applied to biomolecular systems. Redox reactions, and their representation by half-reactions, are key components of biological systems which involve both electrical and chemical domains. A bond graph interpretation of redox reactions is given which combines bond graphs with the Faraday-equivalent chemical potential. This approach is particularly relevant when the biomolecular system implements chemoelectrical transduction - for example chemiosmosis within the key metabolic pathway of mitochondria: oxidative phosphorylation. An alternative way of implementing computational modularity using bond graphs is introduced and used to give a physically based model of the mitochondrial electron transport chain To illustrate the overall approach, this model is analyzed using the Faraday-equivalent chemical potential approach and engineering intuition is used to guide affinity equalisation: a energy based analysis of the mitochondrial electron transport chain.

10 CFR 60.136 - Preclosure controlled area.

Code of Federal Regulations, 2010 CFR

2010-01-01

... limiting of a total effective dose equivalent of 0.05 Sv (5 rem), or the sum of the deep-dose equivalent and the committed dose equivalent to any individual organ or tissue (other than the lens of the eye) of 0.5 Sv (50 rem). The eye dose equivalent shall not exceed 0.15 Sv (15 rem), and the shallow dose...

10 CFR 60.136 - Preclosure controlled area.

Code of Federal Regulations, 2011 CFR

2011-01-01

... limiting of a total effective dose equivalent of 0.05 Sv (5 rem), or the sum of the deep-dose equivalent and the committed dose equivalent to any individual organ or tissue (other than the lens of the eye) of 0.5 Sv (50 rem). The eye dose equivalent shall not exceed 0.15 Sv (15 rem), and the shallow dose...

10 CFR 60.136 - Preclosure controlled area.

Code of Federal Regulations, 2013 CFR

2013-01-01

... limiting of a total effective dose equivalent of 0.05 Sv (5 rem), or the sum of the deep-dose equivalent and the committed dose equivalent to any individual organ or tissue (other than the lens of the eye) of 0.5 Sv (50 rem). The eye dose equivalent shall not exceed 0.15 Sv (15 rem), and the shallow dose...

10 CFR 60.136 - Preclosure controlled area.

Code of Federal Regulations, 2012 CFR

2012-01-01

... limiting of a total effective dose equivalent of 0.05 Sv (5 rem), or the sum of the deep-dose equivalent and the committed dose equivalent to any individual organ or tissue (other than the lens of the eye) of 0.5 Sv (50 rem). The eye dose equivalent shall not exceed 0.15 Sv (15 rem), and the shallow dose...

10 CFR 60.136 - Preclosure controlled area.

Code of Federal Regulations, 2014 CFR

2014-01-01

... limiting of a total effective dose equivalent of 0.05 Sv (5 rem), or the sum of the deep-dose equivalent and the committed dose equivalent to any individual organ or tissue (other than the lens of the eye) of 0.5 Sv (50 rem). The eye dose equivalent shall not exceed 0.15 Sv (15 rem), and the shallow dose...

Chapter D. Effects of Urbanization on Stream Ecosystems in the Willamette River Basin and Surrounding Area, Oregon and Washington

USGS Publications Warehouse

Waite, Ian R.; Sobieszczyk, Steven; Carpenter, Kurt D.; Arnsberg, Andrew J.; Johnson, Henry M.; Hughes, Curt A.; Sarantou, Michael J.; Rinella, Frank A.

2008-01-01

This report describes the effects of urbanization on physical, chemical, and biological characteristics of stream ecosystems in 28 watersheds along a gradient of urbanization in the Willamette River basin and surrounding area, Oregon and Washington, from 2003 through 2005. The study that generated the report is one of several urban-effects studies completed nationally by the U.S. Geological Survey National Water-Quality Assessment Program. Watersheds were selected to minimize natural variability caused by factors such as geology, elevation, and climate, and to maximize coverage of different stages of urban development among watersheds. Because land use or population density alone often are not a complete measure of urbanization, a combination of land use, land cover, infrastructure, and socioeconomic variables were integrated into a multimetric urban intensity index (UII) to represent the degree of urban development in each watershed. Physical characteristics studied include stream hydrology, stream temperature, and habitat; chemical characteristics studied include sulfate, chloride, nutrients, pesticides, dissolved and particulate organic and inorganic carbon, and suspended sediment; and biological characteristics studied include algal, macroinvertebrate, and fish assemblages. Semipermeable membrane devices, passive samplers that concentrate trace levels of hydrophobic organic contaminants such as polycyclic aromatic hydrocarbons and polychlorinated biphenyls, also were used. The objectives of the study were to (1) examine physical, chemical, and biological responses along the gradient of urbanization and (2) determine the major physical, chemical, and landscape variables affecting the structure of aquatic communities. Common effects documented in the literature of urbanization on instream physical, chemical, and biological characteristics, such as increased contaminants, increased streamflow flashiness, increased concentrations of chemicals, and changes in aquatic community structure toward a more tolerant community associated with organically enriched conditions, generally were observed in this study. The strongest correlations to the UII and to many of the algal, macroinvertebrate, and fish assemblage metrics and community ordination involved water-chemistry metrics including the total pesticide concentration, toxic equivalents (extract assay from semipermeable membrane devices), and dissolved oxygen. Hydrologic variability metrics, such as flashiness, that normally are considered to be one of the main processes of urban disturbance had a strong association to the algal and fish assemblages in this study; however, the hydrologic variables for macroinvertebrates were secondary to the water-chemistry metrics mentioned above. Generally, the high urban intensity sites had high abundances of eutrophic and lower dissolved oxygen-indicating diatoms, high abundances of noninsects and tolerant insects, and high abundances of nonnative fish species. On the other hand, the low urban intensity sites had higher abundances of pollution sensitive diatoms, larger numbers of the sensitive macroinvertebrate EPT taxa (Ephemeroptera, Plecoptera and Trichoptera Orders), and fish assemblages with higher abundances of sensitive salmonids. The percent salmonid and macroinvertebrate EPT richness metrics plotted against the UII indicated a possible threshold response at about 25 on the UII, which is equivalent to an impervious surface value of about 5 percent. However, due to the added agricultural land use at sites within the 25 to 60 UII range, this possible threshold probably is not solely due to urbanization, but a combination of urban and agricultural land use. The effects of agricultural and urban land use could not be distinguished from each other, yet combined they provide a good assessment of overall watershed disturbance.

Bioinspired Functional Surfaces for Technological Applications

NASA Astrophysics Data System (ADS)

Sharma, Vipul; Kumar, Suneel; Reddy, Kumbam Lingeshwar; Bahuguna, Ashish; Krishnan, Venkata

2016-08-01

Biological matters have been in continuous encounter with extreme environmental conditions leading to their evolution over millions of years. The fittest have survived through continuous evolution, an ongoing process. Biological surfaces are the important active interfaces between biological matters and the environment, and have been evolving over time to a higher state of intelligent functionality. Bioinspired surfaces with special functionalities have grabbed attention in materials research in the recent times. The microstructures and mechanisms behind these functional biological surfaces with interesting properties have inspired scientists to create artificial materials and surfaces which possess the properties equivalent to their counterparts. In this review, we have described the interplay between unique multiscale (micro- and nano-scale) structures of biological surfaces with intrinsic material properties which have inspired researchers to achieve the desired wettability and functionalities. Inspired by naturally occurring surfaces, researchers have designed and fabricated novel interfacial materials with versatile functionalities and wettability, such as superantiwetting surfaces (superhydrophobic and superoleophobic), omniphobic, switching wettability and water collecting surfaces. These strategies collectively enable functional surfaces to be utilized in different applications such as fog harvesting, surface-enhanced Raman spectroscopy (SERS), catalysis, sensing and biological applications. This paper delivers a critical review of such inspiring biological surfaces and artificial bioinspired surfaces utilized in different applications, where material science and engineering have merged by taking inspiration from the natural systems.

Biologic relativity: Who is the observer and what is observed?

PubMed

Torday, John S; Miller, William B

2016-05-01

When quantum physics and biological phenomena are analogously explored, it emerges that biologic causation must also be understood independently of its overt appearance. This is similar to the manner in which Bohm characterized the explicate versus the implicate order as overlapping frames of ambiguity. Placed in this context, the variables affecting epigenetic inheritance can be properly assessed as a key mechanistic principle of evolution that significantly alters our understanding of homeostasis, pleiotropy, and heterochrony, and the purposes of sexual reproduction. Each of these become differing manifestations of a new biological relativity in which biologic space-time becomes its own frame. In such relativistic cellular contexts, it is proper to question exactly who has observer status, and who and what are being observed. Consideration within this frame reduces biology to cellular information sharing through cell-cell communication to resolve ambiguities at every scope and scale. In consequence, it becomes implicit that eukaryotic evolution derives from the unicellular state, remaining consistently adherent to it in a continuous evolutionary arc based upon elemental, non-stochastic physiologic first principles. Furthermore, the entire cell including its cytoskeletal apparatus and membranes that participate in the resolution of biological uncertainties must be considered as having equivalent primacy with genomes in evolutionary terms. Copyright © 2016 Elsevier Ltd. All rights reserved.

A formal and data-based comparison of measures of motor-equivalent covariation.

PubMed

Verrel, Julius

2011-09-15

Different analysis methods have been developed for assessing motor-equivalent organization of movement variability. In the uncontrolled manifold (UCM) method, the structure of variability is analyzed by comparing goal-equivalent and non-goal-equivalent variability components at the level of elemental variables (e.g., joint angles). In contrast, in the covariation by randomization (CR) approach, motor-equivalent organization is assessed by comparing variability at the task level between empirical and decorrelated surrogate data. UCM effects can be due to both covariation among elemental variables and selective channeling of variability to elemental variables with low task sensitivity ("individual variation"), suggesting a link between the UCM and CR method. However, the precise relationship between the notion of covariation in the two approaches has not been analyzed in detail yet. Analysis of empirical and simulated data from a study on manual pointing shows that in general the two approaches are not equivalent, but the respective covariation measures are highly correlated (ρ > 0.7) for two proposed definitions of covariation in the UCM context. For one-dimensional task spaces, a formal comparison is possible and in fact the two notions of covariation are equivalent. In situations in which individual variation does not contribute to UCM effects, for which necessary and sufficient conditions are derived, this entails the equivalence of the UCM and CR analysis. Implications for the interpretation of UCM effects are discussed. Copyright © 2011 Elsevier B.V. All rights reserved.

Hydroxy acetone and lactic acid synthesis from aqueous propylene glycol/hydrogen peroxide catalysis on Pd-black

DOE Office of Scientific and Technical Information (OSTI.GOV)

Disselkamp, Robert S.; Harris, Benjamin D.; Hart, Todd R.

2008-07-20

The production of polyol chemicals is of increasing interest as they are obtained from the catalytic processing of biological feedstock materials, which also is becoming more prevalent. A case in point is glycerol production, formed as a byproduct in biodiesel catalytic processing. Here we report the reaction of a simple 1,2-diol, propylene glycol, with hydrogen peroxide and a Pd-black catalyst under reflux conditions at 368 K. The experiments were performed by either co-addition of hydrogen peroxide with air sparging, or addition of hydrogen peroxide alone, each yielding hydroxy acetone (HA) and acetic acid (AA) products, with a lesser amount ofmore » lactic acid (LA) formed. Product conversion data at near neutral pH versus hydrogen peroxide equivalents added relative to substrate is presented. Hydrogen peroxide addition without air sparging at 5 equivalents resulted in 65% conversion with an HA:AA molar ratio of 2:1. Conversely, hydrogen peroxide addition with air sparging at only 0.75 equivalents resulted in 40% conversion with an HA:AA ratio of 3:1. From this it is concluded that although the product distribution in these chemistries is somewhat unchanged by air sparging, it is surprising that the amount of reactive oxygen is greatly enhanced with co-addition of O2/H2O2. Additional studies have revealed the amount of LA formed can be enhanced under acidic conditions (pH=1.5 compared to pH=8.5), such that 26% of total product formation is LA. Since hydrogen peroxide is an environmentally clean reagent and becoming more cost effective to use, this work may guide future applied investigations into polyol chemical syntheses.« less

Estimation of potential impacts and natural resource damages of oil.

PubMed

McCay, Deborah French; Rowe, Jill Jennings; Whittier, Nicole; Sankaranarayanan, Sankar; Etkin, Dagmar Schmidt

2004-02-27

Methods were developed to estimate the potential impacts and natural resource damages resulting from oil spills using probabilistic modeling techniques. The oil fates model uses wind data, current data, and transport and weathering algorithms to calculate mass balance of fuel components in various environmental compartments (water surface, shoreline, water column, atmosphere, sediments, etc.), oil pathway over time (trajectory), surface distribution, shoreline oiling, and concentrations of the fuel components in water and sediments. Exposure of aquatic habitats and organisms to whole oil and toxic components is estimated in the biological model, followed by estimation of resulting acute mortality and ecological losses. Natural resource damages are based on estimated costs to restore equivalent resources and/or ecological services, using Habitat Equivalency Analysis (HEA) and Resource Equivalency Analysis (REA) methods. Oil spill modeling was performed for two spill sites in central San Francisco Bay, three spill sizes (20th, 50th, and 95th percentile volumes from tankers and larger freight vessels, based on an analysis of likely spill volumes given a spill has occurred) and four oil types (gasoline, diesel, heavy fuel oil, and crude oil). The scenarios were run in stochastic mode to determine the frequency distribution, mean and standard deviation of fates, impacts, and damages. This work is significant as it demonstrates a statistically quantifiable method for estimating potential impacts and financial consequences that may be used in ecological risk assessment and cost-benefit analyses. The statistically-defined spill volumes and consequences provide an objective measure of the magnitude, range and variability of impacts to wildlife, aquatic organisms and shorelines for potential spills of four oil/fuel types, each having distinct environmental fates and effects.

Biologically Inspired mm-size Gliding UAV

NASA Astrophysics Data System (ADS)

Weihs, Daniel; Zussman, Eyal; Yarin, Alexander

2002-11-01

We present a first design of an unmanned aerial vehicle whose aerodynamic loads are carried by comb-like permeable surfaces. This concept was based on observation and analysis of the flight capabilities of the Thrip family of insects, whose have wings of this form and various plant seeds which use this concept to form an aerodynamic decelerator. This concept is only practical for at low Reynolds numbers, as the viscous trace of bodies moving in fluid becomes thicker as Re becomes smaller. When Re<1, a cylinder moving in fluid can drag along fluid up to several cylinder diameters. This drag effect can be used to produce a comb structure, where the ratio of comb rod to inter-rod distance can be up to 0.1 without significant throughflow, i.e. the comb is equivalent to a continuous surface. To demonstrate this principle, we have built artificial ``dandelion seeds", i.e. stable aerodynamic decelerators (parachutes) made of permeable light mats of submicron diameter nanofibers. We produced the nanofiber matrices (mats) by electrospinning of polymer solutions, obtaining fibers of 200-400 nm diameter. These fibers were then deposited on frames that serve to define the aerodynamic surfaces, thus producing the mat, with controllable density. For stability, the aerodynamic surfaces had positive dihedral ( inverted umbrella) forms with the fuselage hanging below. When dropped, the platforms fell freely through the air, apex down, reaching terminal velocity very quickly. By comparing the sink rate of the permeable structures with equivalent decelerators with continuous (Saran-wrap) surfaces we show that the permeable surfaces are equivalent to continuous surfaces, with significant weight savings, as long as the local Reynolds number is o(1).

Biological effect on drug distribution and vascular healing via paclitaxel-coated balloon technology in drug eluting stent restenosis swine model.

PubMed

Li, Yan; Tellez, Armando; Rousselle, Serge D; Dillon, Krista N; Garza, Javier A; Barry, Chris; Granada, Juan F

2016-07-01

To evaluate the biological effect of a paclitaxel-coated balloon (PCB) technology on vascular drug distribution and healing in drug eluting stent restenosis (DES-ISR) swine model. The mechanism of action and healing response via PCB technology in DES-ISR is not completely understood. A total of 27 bare metal stents were implanted in coronary arteries and 30 days later the in-stent restenosis was treated with PCB. Treated segments were harvested at 1 hr, 14 days and 30 days post treatment for the pharmacokinetic analysis. In addition, 24 DES were implanted in coronary arteries for 30 days, then all DES-ISRs were treated with either PCB (n = 12) or uncoated balloon (n = 12). At day 60, vessels were harvested for histology following angiography and optical coherence tomography (OCT). The paclitaxel level in neointimal tissue was about 18 times higher (P = 0.0004) at 1 hr Cmax , and retained about five times higher (P = 0.008) at day 60 than that in vessel wall. A homogenous distribution of paclitaxel in ISR was demonstrated by using fluorescently labeled paclitaxel. Notably, in DES-ISR, both termination OCT and quantitative coronary angioplasty showed a significant neointimal reduction and less late lumen loss (P = 0.05 and P = 0.03, respectively) post PCB versus post uncoated balloon. The PES-ISR + PCB group displayed higher levels of peri-strut inflammation and fibrin scores compared to the -limus DES-ISR + PCB group. In ISR, paclitaxel is primarily deposited in neointimal tissue and effectively retained over time following PCB use. Despite the presence of metallic struts, a uniform distribution was characterized. PCB demonstrated an equivalent biological effect in DES-ISR without significantly increasing inflammation. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Biological effect on drug distribution and vascular healing via paclitaxel‐coated balloon technology in drug eluting stent restenosis swine model

PubMed Central

Li, Yan; Tellez, Armando; Rousselle, Serge D.; Dillon, Krista N.; Garza, Javier A.; Barry, Chris

2015-01-01

Objectives To evaluate the biological effect of a paclitaxel‐coated balloon (PCB) technology on vascular drug distribution and healing in drug eluting stent restenosis (DES‐ISR) swine model. Background The mechanism of action and healing response via PCB technology in DES‐ISR is not completely understood. Methods A total of 27 bare metal stents were implanted in coronary arteries and 30 days later the in‐stent restenosis was treated with PCB. Treated segments were harvested at 1 hr, 14 days and 30 days post treatment for the pharmacokinetic analysis. In addition, 24 DES were implanted in coronary arteries for 30 days, then all DES‐ISRs were treated with either PCB (n = 12) or uncoated balloon (n = 12). At day 60, vessels were harvested for histology following angiography and optical coherence tomography (OCT). Results The paclitaxel level in neointimal tissue was about 18 times higher (P = 0.0004) at 1 hr C max, and retained about five times higher (P = 0.008) at day 60 than that in vessel wall. A homogenous distribution of paclitaxel in ISR was demonstrated by using fluorescently labeled paclitaxel. Notably, in DES‐ISR, both termination OCT and quantitative coronary angioplasty showed a significant neointimal reduction and less late lumen loss (P = 0.05 and P = 0.03, respectively) post PCB versus post uncoated balloon. The PES‐ISR + PCB group displayed higher levels of peri‐strut inflammation and fibrin scores compared to the ‐limus DES‐ISR + PCB group. Conclusions In ISR, paclitaxel is primarily deposited in neointimal tissue and effectively retained over time following PCB use. Despite the presence of metallic struts, a uniform distribution was characterized. PCB demonstrated an equivalent biological effect in DES‐ISR without significantly increasing inflammation. © 2015 Wiley Periodicals, Inc. PMID:26613810

Modeling study of radiation effects on thrombocytopoietic and granulocytopoietic systems in humans

NASA Astrophysics Data System (ADS)

Smirnova, O. A.

2011-07-01

Biologically motivated mathematical models, which describe the dynamics of thrombocytopoiesis and granulocytopoiesis in nonirradiated and irradiated humans, are developed. These models, being based on conventional biological theories, are implemented as the systems of nonlinear differential equations whose variables and constant parameters have clear biological meaning. Thorough analytical and numerical analysis of the proposed models is performed. It is found that the models on hand are capable of reproducing the dynamical regimes which are typical for the thrombocytopoiesis and granulocytopoiesis in the norm and in the case of hematological disorders, such as cyclic thrombocytopenia and cyclic neutropenia. The elaborated models are applied to investigate the dynamics of thrombocytopoiesis and granulocytopoiesis in astronauts exposed to space radiation during long-term missions such as voyages to Mars. The dose rate equivalent for space radiation (galactic cosmic rays (GCR) and solar particles event (SPE)) is taken as a variable parameter of the models. It is revealed that the thrombocytopoietic and granulocytopoietic systems can adapt themselves to GCR exposure. It is also shown that an SPE causes damped oscillations of the "effective" radiosensitivity of these cell systems that, in turn, determines the strength of their responses to the subsequent SPE. Specifically, depending on the time interval between SPEs, the preceding SPE can induce either radiosensitization or radioprotection effects on the thrombocytopoietic and granulocytopoietic systems. In the last case, adaptive responses to the subsequent SPE in these systems occur. All this testifies to the efficiency of employment of the developed models in investigation and prediction of effects of space radiation on the thrombocytopoietic and granulocytopoietic systems. The developed models of these vital body systems provide a better understanding of the risks to health from the solar particles events and enable one to evaluate the need of operational applications of countermeasures for astronauts in the long-term space missions.

Collection of biological and non-biological particles by new and used filters made from glass and electrostatically charged synthetic fibers.

PubMed

Raynor, P C; Kim, B G; Ramachandran, G; Strommen, M R; Horns, J H; Streifel, A J

2008-02-01

Synthetic filters made from fibers carrying electrostatic charges and fiberglass filters that do not carry electrostatic charges are both utilized commonly in heating, ventilating, and air-conditioning (HVAC) systems. The pressure drop and efficiency of a bank of fiberglass filters and a bank of electrostatically charged synthetic filters were measured repeatedly for 13 weeks in operating HVAC systems at a hospital. Additionally, the efficiency with which new and used fiberglass and synthetic filters collected culturable biological particles was measured in a test apparatus. Pressure drop measurements adjusted to equivalent flows indicated that the synthetic filters operated with a pressure drop less than half that of the fiberglass filters throughout the test. When measured using total ambient particles, synthetic filter efficiency decreased during the test period for all particle diameters. For particles 0.7-1.0 mum in diameter, efficiency decreased from 92% to 44%. It is hypothesized that this reduction in collection efficiency may be due to charge shielding. Efficiency did not change significantly for the fiberglass filters during the test period. However, when measured using culturable biological particles in the ambient air, efficiency was essentially the same for new filters and filters used for 13 weeks in the hospital for both the synthetic and fiberglass filters. It is hypothesized that the lack of efficiency reduction for culturable particles may be due to their having higher charge than non-biological particles, allowing them to overcome the effects of charge shielding. The type of particles requiring capture may be an important consideration when comparing the relative performance of electrostatically charged synthetic and fiberglass filters. Electrostatically charged synthetic filters with high initial efficiency can frequently replace traditional fiberglass filters with lower efficiency in HVAC systems because properly designed synthetic filters offer less resistance to air flow. Although the efficiency of charged synthetic filters at collecting non-biological particles declined substantially with use, the efficiency of these filters at collecting biological particles remained steady. These findings suggest that the merits of electrostatically charged synthetic HVAC filters relative to fiberglass filters may be more pronounced if collection of biological particles is of primary concern.

10 CFR Appendix B to Part 20 - Annual Limits on Intake (ALIs) and Derived Air Concentrations (DACs) of Radionuclides for...

Code of Federal Regulations, 2014 CFR

2014-01-01

...) a committed effective dose equivalent of 5 rems (stochastic ALI) or (2) a committed dose equivalent of 50 rems to an organ or tissue (non-stochastic ALI). The stochastic ALIs were derived to result in... equivalent to the whole body of 5 rems. The derivation includes multiplying the committed dose equivalent to...

10 CFR Appendix B to Part 20 - Annual Limits on Intake (ALIs) and Derived Air Concentrations (DACs) of Radionuclides for...

Code of Federal Regulations, 2011 CFR

2011-01-01

...) a committed effective dose equivalent of 5 rems (stochastic ALI) or (2) a committed dose equivalent of 50 rems to an organ or tissue (non-stochastic ALI). The stochastic ALIs were derived to result in... equivalent to the whole body of 5 rems. The derivation includes multiplying the committed dose equivalent to...

10 CFR Appendix B to Part 20 - Annual Limits on Intake (ALIs) and Derived Air Concentrations (DACs) of Radionuclides for...

Code of Federal Regulations, 2012 CFR

2012-01-01

...) a committed effective dose equivalent of 5 rems (stochastic ALI) or (2) a committed dose equivalent of 50 rems to an organ or tissue (non-stochastic ALI). The stochastic ALIs were derived to result in... equivalent to the whole body of 5 rems. The derivation includes multiplying the committed dose equivalent to...

10 CFR Appendix B to Part 20 - Annual Limits on Intake (ALIs) and Derived Air Concentrations (DACs) of Radionuclides for...

Code of Federal Regulations, 2010 CFR

2010-01-01

...) a committed effective dose equivalent of 5 rems (stochastic ALI) or (2) a committed dose equivalent of 50 rems to an organ or tissue (non-stochastic ALI). The stochastic ALIs were derived to result in... equivalent to the whole body of 5 rems. The derivation includes multiplying the committed dose equivalent to...

10 CFR Appendix B to Part 20 - Annual Limits on Intake (ALIs) and Derived Air Concentrations (DACs) of Radionuclides for...

Code of Federal Regulations, 2013 CFR

2013-01-01

...) a committed effective dose equivalent of 5 rems (stochastic ALI) or (2) a committed dose equivalent of 50 rems to an organ or tissue (non-stochastic ALI). The stochastic ALIs were derived to result in... equivalent to the whole body of 5 rems. The derivation includes multiplying the committed dose equivalent to...

Comparisons of Internet-Based and Face-to-Face Learning Systems Based on "Equivalency of Experiences" According to Students' Academic Achievements and Satisfactions

ERIC Educational Resources Information Center

Karatas, Sercin; Simsek, Nurettin

2009-01-01

The purpose of this study is to determine whether "equivalent learning experiences" ensure equivalency, in the Internet-based and face-to-face interaction methods on learning results and student satisfaction. In the experimental process of this study, the effect of the Internet-based and face-to-face learning on the equivalency in…

LTI system order reduction approach based on asymptotical equivalence and the Co-operation of biology-related algorithms

NASA Astrophysics Data System (ADS)

Ryzhikov, I. S.; Semenkin, E. S.; Akhmedova, Sh A.

2017-02-01

A novel order reduction method for linear time invariant systems is described. The method is based on reducing the initial problem to an optimization one, using the proposed model representation, and solving the problem with an efficient optimization algorithm. The proposed method of determining the model allows all the parameters of the model with lower order to be identified and by definition, provides the model with the required steady-state. As a powerful optimization tool, the meta-heuristic Co-Operation of Biology-Related Algorithms was used. Experimental results proved that the proposed approach outperforms other approaches and that the reduced order model achieves a high level of accuracy.

Estimating equivalence with quantile regression

USGS Publications Warehouse

Cade, B.S.

2011-01-01

Equivalence testing and corresponding confidence interval estimates are used to provide more enlightened statistical statements about parameter estimates by relating them to intervals of effect sizes deemed to be of scientific or practical importance rather than just to an effect size of zero. Equivalence tests and confidence interval estimates are based on a null hypothesis that a parameter estimate is either outside (inequivalence hypothesis) or inside (equivalence hypothesis) an equivalence region, depending on the question of interest and assignment of risk. The former approach, often referred to as bioequivalence testing, is often used in regulatory settings because it reverses the burden of proof compared to a standard test of significance, following a precautionary principle for environmental protection. Unfortunately, many applications of equivalence testing focus on establishing average equivalence by estimating differences in means of distributions that do not have homogeneous variances. I discuss how to compare equivalence across quantiles of distributions using confidence intervals on quantile regression estimates that detect differences in heterogeneous distributions missed by focusing on means. I used one-tailed confidence intervals based on inequivalence hypotheses in a two-group treatment-control design for estimating bioequivalence of arsenic concentrations in soils at an old ammunition testing site and bioequivalence of vegetation biomass at a reclaimed mining site. Two-tailed confidence intervals based both on inequivalence and equivalence hypotheses were used to examine quantile equivalence for negligible trends over time for a continuous exponential model of amphibian abundance. ?? 2011 by the Ecological Society of America.

Substantial equivalence analysis in fruits from three Theobroma species through chemical composition and protein profiling.

PubMed

Pérez-Mora, Walter; Jorrin-Novo, Jesús V; Melgarejo, Luz Marina

2018-02-01

Substantial equivalence studies were performed in three Theobroma spp., cacao, bicolor and grandiflorum through chemical composition analysis and protein profiling of fruit (pulp juice and seeds). Principal component analysis of sugar, organic acid, and phenol content in pulp juice revealed equivalence among the three species, with differences in some of the compounds that may result in different organoleptic properties. Proteins were extracted from seeds and pulp juice, resolved by two dimensional electrophoresis and major spots subjected to mass spectrometry analysis and identification. The protein profile, as revealed by principal component analysis, was variable among the three species in both seed and pulp, with qualitative and quantitative differences in some of protein species. The functional grouping of the identified proteins correlated with the biological role of each organ. Some of the identified proteins are of interest, being minimally discussed, including vicilin, a protease inhibitor, and a flavonol synthase/flavanone 3-hydroxylase. Theobroma grandiflorum and Theobroma bicolor are endemic Amazonian plants that are poorly traded at the local level. As close relatives of Theobroma cacao, they may provide a good alternative for human consumption and industrial purposes. In this regard, we performed equivalence studies by conducting a comparative biochemical and proteomics analysis of the fruit, pulp juice and seeds of these three species. The results indicated equivalent chemical compositions and variable protein profiles with some differences in the content of the specific compounds or protein species that may result in variable organoleptic properties between the species and can be exploited for traceability purposes. Copyright © 2017 Elsevier Ltd. All rights reserved.

The Principle of Equivalence: Demonstrations of Local Effective Vertical and Horizontal

ERIC Educational Resources Information Center

Munera, Hector A.

2010-01-01

It has been suggested that Einstein's principle of equivalence (PE) should be introduced at an early stage. This principle leads to the notion of local effective gravity, which in turn defines effective vertical and horizontal directions. Local effective gravity need not coincide with the direction of terrestrial gravity. This paper describes…

Equivalent complex conductivities representing the effects of T-tubules and folded surface membranes on the electrical admittance and impedance of skeletal muscles measured by external-electrode method

NASA Astrophysics Data System (ADS)

Sekine, Katsuhisa

2017-12-01

In order to represent the effects of T-tubules and folded surface membranes on the electrical admittance and impedance of skeletal muscles measured by the external-electrode method, analytical relations for the equivalent complex conductivities of hypothetical smooth surface membranes were derived. In the relations, the effects of each tubule were represented by the admittance of a straight cable. The effects of the folding of a surface membrane were represented by the increased area of surface membranes. The equivalent complex conductivities were represented as summation of these effects, and the effects of the T-tubules were different between the transversal and longitudinal directions. The validity of the equivalent complex conductivities was supported by the results of finite-difference method (FDM) calculations made using three-dimensional models in which T-tubules and folded surface membranes were represented explicitly. FDM calculations using the equivalent complex conductivities suggested that the electrically inhomogeneous structure due to the existence of muscle cells with T-tubules was sufficient for explaining the experimental results previously obtained using the external-electrode method. Results of FDM calculations in which the structural changes caused by muscle contractions were taken into account were consistent with the reported experimental results.

Action video game players' visual search advantage extends to biologically relevant stimuli.

PubMed

Chisholm, Joseph D; Kingstone, Alan

2015-07-01

Research investigating the effects of action video game experience on cognition has demonstrated a host of performance improvements on a variety of basic tasks. Given the prevailing evidence that these benefits result from efficient control of attentional processes, there has been growing interest in using action video games as a general tool to enhance everyday attentional control. However, to date, there is little evidence indicating that the benefits of action video game playing scale up to complex settings with socially meaningful stimuli - one of the fundamental components of our natural environment. The present experiment compared action video game player (AVGP) and non-video game player (NVGP) performance on an oculomotor capture task that presented participants with face stimuli. In addition, the expression of a distractor face was manipulated to assess if action video game experience modulated the effect of emotion. Results indicate that AVGPs experience less oculomotor capture than NVGPs; an effect that was not influenced by the emotional content depicted by distractor faces. It is noteworthy that this AVGP advantage emerged despite participants being unaware that the investigation had to do with video game playing, and participants being equivalent in their motivation and treatment of the task as a game. The results align with the notion that action video game experience is associated with superior attentional and oculomotor control, and provides evidence that these benefits can generalize to more complex and biologically relevant stimuli. Copyright © 2015 Elsevier B.V. All rights reserved.

Radical Scavenging and Anti-Inflammatory Activities of Representative Anthocyanin Groupings from Pigment-Rich Fruits and Vegetables

PubMed Central

Calabriso, Nadia; Berland, Helge; Maiorano, Gabriele; Gerardi, Carmela; Carluccio, Maria Annunziata; Andersen, Øyvind M.

2018-01-01

Anthocyanins, the naturally occurring pigments responsible for most red to blue colours of flowers, fruits and vegetables, have also attracted interest because of their potential health effects. With the aim of contributing to major insights into their structure–activity relationship (SAR), we have evaluated the radical scavenging and biological activities of selected purified anthocyanin samples (PASs) from various anthocyanin-rich plant materials: two fruits (mahaleb cherry and blackcurrant) and two vegetables (black carrot and “Sun Black” tomato), differing in anthocyanin content (ranging from 4.9 to 38.5 mg/g DW) and molecular structure of the predominant anthocyanins. PASs from the abovementioned plant materials have been evaluated for their antioxidant capacity using Trolox Equivalent Antioxidant Capacity (TEAC) and Oxygen Radical Absorbance Capacity (ORAC) assays. In human endothelial cells, we analysed the anti-inflammatory activity of different PASs by measuring their effects on the expression of endothelial adhesion molecules VCAM-1 and ICAM-1. We demonstrated that all the different PASs showed biological activity. They exhibited antioxidant capacity of different magnitude, higher for samples containing non-acylated anthocyanins (typical for fruits) compared to samples containing more complex anthocyanins acylated with cinnamic acid derivatives (typical for vegetables), even though this order was slightly reversed when ORAC assay values were expressed on a molar basis. Concordantly, PASs containing non-acylated anthocyanins reduced the expression of endothelial inflammatory antigens more than samples with aromatic acylated anthocyanins, suggesting the potential beneficial effect of structurally diverse anthocyanins in cardiovascular protection. PMID:29316619

Effect of land management on soil properties in flood irrigated citrus orchards in Eastern Spain

NASA Astrophysics Data System (ADS)

Morugán-Coronado, A.; García-Orenes, F.; Cerdà, A.

2015-01-01

Agricultural land management greatly affects soil properties. Microbial soil communities are the most sensitive and rapid indicators of perturbations in land use and soil enzyme activities are sensitive biological indicators of the effects of soil management practices. Citrus orchards frequently have degraded soils and this paper evaluates how land management in citrus orchards can improve soil quality. A field experiment was performed in an orchard of orange trees (Citrus Sinensis) in the Alcoleja Experimental Station (Eastern Spain) with clay-loam agricultural soils to assess the long-term effects of herbicides with inorganic fertilizers (H), intensive ploughing and inorganic fertilizers (P) and organic farming (O) on the soil microbial properties, and to study the relationship between them. Nine soil samples were taken from each agricultural management plot. In all the samples the basal soil respiration, soil microbial biomass carbon, water holding capacity, electrical conductivity, soil organic matter, total nitrogen, available phosphorus, available potassium, aggregate stability, cation exchange capacity, pH, texture, macronutrients (Na, Ca and Mg), micronutrients (Fe, Mn, Zn and Cu), calcium carbonate equivalent, calcium carbonate content of limestone and enzimatic activities (urease, dehydrogenase, β-glucosidase and acid phosphatase) were determined. The results showed a substantial level of differentiation in the microbial properties, which were highly associated with soil organic matter content. The management practices including herbicides and intensive ploughing had similar results on microbial soil properties. O management contributed to an increase in the soil biology quality, aggregate stability and organic matter content.

Determination of prescription dose for Cs-131 permanent implants using the BED formalism including resensitization correction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Luo, Wei, E-mail: wei.luo@uky.edu; Molloy, Janelle; Aryal, Prakash

2014-02-15

Purpose: The current widely used biological equivalent dose (BED) formalism for permanent implants is based on the linear-quadratic model that includes cell repair and repopulation but not resensitization (redistribution and reoxygenation). The authors propose a BED formalism that includes all the four biological effects (4Rs), and the authors propose how it can be used to calculate appropriate prescription doses for permanent implants with Cs-131. Methods: A resensitization correction was added to the BED calculation for permanent implants to account for 4Rs. Using the same BED, the prescription doses with Au-198, I-125, and Pd-103 were converted to the isoeffective Cs-131 prescriptionmore » doses. The conversion factor F, ratio of the Cs-131 dose to the equivalent dose with the other reference isotope (F{sub r}: with resensitization, F{sub n}: without resensitization), was thus derived and used for actual prescription. Different values of biological parameters such as α, β, and relative biological effectiveness for different types of tumors were used for the calculation. Results: Prescription doses with I-125, Pd-103, and Au-198 ranging from 10 to 160 Gy were converted into prescription doses with Cs-131. The difference in dose conversion factors with (F{sub r}) and without (F{sub n}) resensitization was significant but varied with different isotopes and different types of tumors. The conversion factors also varied with different doses. For I-125, the average values of F{sub r}/F{sub n} were 0.51/0.46, for fast growing tumors, and 0.88/0.77 for slow growing tumors. For Pd-103, the average values of F{sub r}/F{sub n} were 1.25/1.15 for fast growing tumors, and 1.28/1.22 for slow growing tumors. For Au-198, the average values of F{sub r}/F{sub n} were 1.08/1.25 for fast growing tumors, and 1.00/1.06 for slow growing tumors. Using the biological parameters for the HeLa/C4-I cells, the averaged value of F{sub r} was 1.07/1.11 (rounded to 1.1), and the averaged value of F{sub n} was 1.75/1.18. F{sub r} of 1.1 has been applied to gynecological cancer implants with expected acute reactions and outcomes as expected based on extensive experience with permanent implants. The calculation also gave the average Cs-131 dose of 126 Gy converted from the I-125 dose of 144 Gy for prostate implants. Conclusions: Inclusion of an allowance for resensitization led to significant dose corrections for Cs-131 permanent implants, and should be applied to prescription dose calculation. The adjustment of the Cs-131 prescription doses with resensitization correction for gynecological permanent implants was consistent with clinical experience and observations. However, the Cs-131 prescription doses converted from other implant doses can be further adjusted based on new experimental results, clinical observations, and clinical outcomes.« less

Determination of prescription dose for Cs-131 permanent implants using the BED formalism including resensitization correction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Luo, Wei, E-mail: wei.luo@uky.edu; Molloy, Janelle; Aryal, Prakash

Purpose: The current widely used biological equivalent dose (BED) formalism for permanent implants is based on the linear-quadratic model that includes cell repair and repopulation but not resensitization (redistribution and reoxygenation). The authors propose a BED formalism that includes all the four biological effects (4Rs), and the authors propose how it can be used to calculate appropriate prescription doses for permanent implants with Cs-131. Methods: A resensitization correction was added to the BED calculation for permanent implants to account for 4Rs. Using the same BED, the prescription doses with Au-198, I-125, and Pd-103 were converted to the isoeffective Cs-131 prescriptionmore » doses. The conversion factor F, ratio of the Cs-131 dose to the equivalent dose with the other reference isotope (F{sub r}: with resensitization, F{sub n}: without resensitization), was thus derived and used for actual prescription. Different values of biological parameters such as α, β, and relative biological effectiveness for different types of tumors were used for the calculation. Results: Prescription doses with I-125, Pd-103, and Au-198 ranging from 10 to 160 Gy were converted into prescription doses with Cs-131. The difference in dose conversion factors with (F{sub r}) and without (F{sub n}) resensitization was significant but varied with different isotopes and different types of tumors. The conversion factors also varied with different doses. For I-125, the average values of F{sub r}/F{sub n} were 0.51/0.46, for fast growing tumors, and 0.88/0.77 for slow growing tumors. For Pd-103, the average values of F{sub r}/F{sub n} were 1.25/1.15 for fast growing tumors, and 1.28/1.22 for slow growing tumors. For Au-198, the average values of F{sub r}/F{sub n} were 1.08/1.25 for fast growing tumors, and 1.00/1.06 for slow growing tumors. Using the biological parameters for the HeLa/C4-I cells, the averaged value of F{sub r} was 1.07/1.11 (rounded to 1.1), and the averaged value of F{sub n} was 1.75/1.18. F{sub r} of 1.1 has been applied to gynecological cancer implants with expected acute reactions and outcomes as expected based on extensive experience with permanent implants. The calculation also gave the average Cs-131 dose of 126 Gy converted from the I-125 dose of 144 Gy for prostate implants. Conclusions: Inclusion of an allowance for resensitization led to significant dose corrections for Cs-131 permanent implants, and should be applied to prescription dose calculation. The adjustment of the Cs-131 prescription doses with resensitization correction for gynecological permanent implants was consistent with clinical experience and observations. However, the Cs-131 prescription doses converted from other implant doses can be further adjusted based on new experimental results, clinical observations, and clinical outcomes.« less

Biosimilars: Considerations for Oncology Nurses
.

PubMed

Vizgirda, Vida; Jacobs, Ira

2017-04-01

Biosimilars are developed to be highly similar to and treat the same conditions as licensed biologics. As they are approved and their use becomes more widespread, oncology nurses should be aware of their development and unique considerations. This article reviews properties of biosimilars; their regulation and approval process; the ways in which their quality, safety, and efficacy are evaluated; their postmarketing safety monitoring; and their significance to oncology nurses and oncology nursing.
. A search of PubMed and regulatory agency websites was conducted for references related to the development and use of biosimilars in oncology. 
. Because biologics are large, structurally complex molecules, biosimilars cannot be considered generic equivalents to licensed biologic products. Consequently, regulatory approval for biosimilars is different from approval for small-molecule generics. Oncology nurses are in a unique position to educate themselves, other clinicians, and patients and their families about biosimilars to ensure accurate understanding, as well as optimal and safe use, of biosimilars.

Fluorescence dynamics of biological systems using synchrotron radiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gratton, E.; Mantulin, W.W.; Weber, G.

1996-09-01

A beamline for time-resolved fluorescence spectroscopy of biological systems is under construction at the Synchrotron Radiation Center. The fluorometer, operating in the frequency domain, will take advantage of the time structure of the synchrotron radiation light pulses to determine fluorescence lifetimes. Using frequency-domain techniques, the instrument can achieve an ultimate time resolution on the order of picoseconds. Preliminary experiments have shown that reducing the intensity of one of the fifteen electron bunches in the storage ring allows measurement of harmonic frequencies equivalent to the single-bunch mode. This mode of operation of the synchrotron significantly extends the range of lifetimes thatmore » can be measured. The wavelength range (encompassing the visible and ultraviolet), the range of measurable lifetimes, and the stability and reproducibility of the storage ring pulses should make this beamline a versatile tool for the investigation of the complex fluorescence decay of biological systems. {copyright} {ital 1996 American Institute of Physics.}« less

Biological-inorganic hybrid systems as a generalized platform for chemical production.

PubMed

Nangle, Shannon N; Sakimoto, Kelsey K; Silver, Pamela A; Nocera, Daniel G

2017-12-01

An expanding renewable energy market to supplant petrochemicals has motivated synthesis technologies that use renewable feedstocks, such as CO 2 . Hybrid biological-inorganic systems provide a sustainable, efficient, versatile, and inexpensive chemical synthesis platform. These systems comprise biocompatible electrodes that transduce electrical energy either directly or indirectly into bioavailable energy, such as H 2 and NAD(P)H. In combination, specific bacteria use these energetic reducing equivalents to fix CO 2 into multi-carbon organic compounds. As hybrid biological-inorganic technologies have developed, the focus has shifted from phenomenological and proof-of-concept discovery towards enhanced energy efficiency, production rate, product scope, and industrial robustness. In this review, we highlight the progress and the state-of-the-art of this field and describe the advantages and challenges involved in designing bio- and chemo- compatible systems. Copyright © 2017 Elsevier Ltd. All rights reserved.

Fluorogenic RNA Mango aptamers for imaging small non-coding RNAs in mammalian cells.

PubMed

Autour, Alexis; C Y Jeng, Sunny; D Cawte, Adam; Abdolahzadeh, Amir; Galli, Angela; Panchapakesan, Shanker S S; Rueda, David; Ryckelynck, Michael; Unrau, Peter J

2018-02-13

Despite having many key roles in cellular biology, directly imaging biologically important RNAs has been hindered by a lack of fluorescent tools equivalent to the fluorescent proteins available to study cellular proteins. Ideal RNA labelling systems must preserve biological function, have photophysical properties similar to existing fluorescent proteins, and be compatible with established live and fixed cell protein labelling strategies. Here, we report a microfluidics-based selection of three new high-affinity RNA Mango fluorogenic aptamers. Two of these are as bright or brighter than enhanced GFP when bound to TO1-Biotin. Furthermore, we show that the new Mangos can accurately image the subcellular localization of three small non-coding RNAs (5S, U6, and a box C/D scaRNA) in fixed and live mammalian cells. These new aptamers have many potential applications to study RNA function and dynamics both in vitro and in mammalian cells.

Synthesis and biological evaluation of novel tetrahydroisoquinoline-C-aryl glucosides as SGLT2 inhibitors for the treatment of type 2 diabetes.

PubMed

Pan, Xuan; Huan, Yi; Shen, Zhufang; Liu, Zhanzhu

2016-05-23

A series of novel tetrahydroisoquinoline-C-aryl glucosides has been synthesized and evaluated for the inhibition of human SGLT2. Compared with dapagliflozin, compound 13h exhibited equivalent in vitro inhibitory activity against SGLT2, which might become a promising candidate for the treatment of type 2 diabetes. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Chemoselective ratiometric imaging of protein S-sulfenylation.

PubMed

Tom, Christopher T M B; Crellin, John E; Motiwala, Hashim F; Stone, Matthew B; Davda, Dahvid; Walker, William; Kuo, Yu-Hsuan; Hernandez, Jeannie L; Labby, Kristin J; Gomez-Rodriguez, Lyanne; Jenkins, Paul M; Veatch, Sarah L; Martin, Brent R

2017-06-29

Here we report a ratiometric fluorescent probe for chemoselective conjugation to sulfenic acids in living cells. Our approach couples an α-fluoro-substituted dimedone to an aminonaphthalene fluorophore (F-DiNap), which upon sulfenic acid conjugation is locked as the 1,3-diketone, changing the fluorophore excitation. F-DiNap reacts with S-sulfenylated proteins at equivalent rates to current probes, but the α-fluorine substitution blocks side-reactions with biological aldehydes.

Structural constraints on the three-dimensional geometry of simple viruses: case studies of a new predictive tool

PubMed Central

Keef, Thomas; Wardman, Jessica P.; Ranson, Neil A.; Stockley, Peter G.; Twarock, Reidun

2013-01-01

Understanding the fundamental principles of virus architecture is one of the most important challenges in biology and medicine. Crick and Watson were the first to propose that viruses exhibit symmetry in the organization of their protein containers for reasons of genetic economy. Based on this, Caspar and Klug introduced quasi-equivalence theory to predict the relative locations of the coat proteins within these containers and classified virus structure in terms of T-numbers. Here it is shown that quasi-equivalence is part of a wider set of structural constraints on virus structure. These constraints can be formulated using an extension of the underlying symmetry group and this is demonstrated with a number of case studies. This new concept in virus biology provides for the first time predictive information on the structural constraints on coat protein and genome topography, and reveals a previously unrecognized structural interdependence of the shapes and sizes of different viral components. It opens up the possibility of distinguishing the structures of different viruses with the same T-number, suggesting a refined viral structure classification scheme. It can moreover be used as a basis for models of virus function, e.g. to characterize the start and end configurations of a structural transition important for infection. PMID:23403965

Structural constraints on the three-dimensional geometry of simple viruses: case studies of a new predictive tool.

PubMed

Keef, Thomas; Wardman, Jessica P; Ranson, Neil A; Stockley, Peter G; Twarock, Reidun

2013-03-01

Understanding the fundamental principles of virus architecture is one of the most important challenges in biology and medicine. Crick and Watson were the first to propose that viruses exhibit symmetry in the organization of their protein containers for reasons of genetic economy. Based on this, Caspar and Klug introduced quasi-equivalence theory to predict the relative locations of the coat proteins within these containers and classified virus structure in terms of T-numbers. Here it is shown that quasi-equivalence is part of a wider set of structural constraints on virus structure. These constraints can be formulated using an extension of the underlying symmetry group and this is demonstrated with a number of case studies. This new concept in virus biology provides for the first time predictive information on the structural constraints on coat protein and genome topography, and reveals a previously unrecognized structural interdependence of the shapes and sizes of different viral components. It opens up the possibility of distinguishing the structures of different viruses with the same T-number, suggesting a refined viral structure classification scheme. It can moreover be used as a basis for models of virus function, e.g. to characterize the start and end configurations of a structural transition important for infection.

Synthesis and biological activity of chimeric structures derived from the cytotoxic natural compounds dolastatin 10 and dolastatin 15.

PubMed

Poncet, J; Busquet, M; Roux, F; Pierré, A; Atassi, G; Jouin, P

1998-04-23

The natural cytotoxic compounds dolastatins 10 and 15 exhibit great similarities in structure and in their biological activity profiles. Two compounds (1 and 2) formed by interchanging the dolaisoleuine residue of dolastatin 10 and the MeVal-Pro dipeptide of dolastatin 15 were synthesized in order to evaluate the possible equivalence of these units. These compounds can be considered as chimeras of dolastatins 10 and 15 formed by the N-terminal part of the former and the C-terminal part of the latter and vice versa. Both analogues exhibited a marked decrease in their cytotoxic activity but showed similar differential cytotoxicity with regard to the cell lines assayed compared with the parent compounds. HT-29 cell line was the least sensitive one. However, this activity was in the nanomolar level and close to that of vincristine. The differences in their effect on tubulin polymerization were less pronounced. We confirmed the already known crucial role of the Dil residue in this assay. The nonequivalence of the Dil unit and the MeVal-Pro dipeptide probably reflects modification in the relative positions of the N-dimethylamino and the phenyl moieties.

Intra-body microwave communication through adipose tissue.

PubMed

Asan, Noor Badariah; Noreland, Daniel; Hassan, Emadeldeen; Redzwan Mohd Shah, Syaiful; Rydberg, Anders; Blokhuis, Taco J; Carlsson, Per-Ola; Voigt, Thiemo; Augustine, Robin

2017-08-01

The human body can act as a medium for the transmission of electromagnetic waves in the wireless body sensor networks context. However, there are transmission losses in biological tissues due to the presence of water and salts. This Letter focuses on lateral intra-body microwave communication through different biological tissue layers and demonstrates the effect of the tissue thicknesses by comparing signal coupling in the channel. For this work, the authors utilise the R-band frequencies since it overlaps the industrial, scientific and medical radio (ISM) band. The channel model in human tissues is proposed based on electromagnetic simulations, validated using equivalent phantom and ex-vivo measurements. The phantom and ex-vivo measurements are compared with simulation modelling. The results show that electromagnetic communication is feasible in the adipose tissue layer with a low attenuation of ∼2 dB per 20 mm for phantom measurements and 4 dB per 20 mm for ex-vivo measurements at 2 GHz. Since the dielectric losses of human adipose tissues are almost half of ex-vivo tissue, an attenuation of around 3 dB per 20 mm is expected. The results show that human adipose tissue can be used as an intra-body communication channel.

Influence of climate on malaria transmission depends on daily temperature variation.

PubMed

Paaijmans, Krijn P; Blanford, Simon; Bell, Andrew S; Blanford, Justine I; Read, Andrew F; Thomas, Matthew B

2010-08-24

Malaria transmission is strongly influenced by environmental temperature, but the biological drivers remain poorly quantified. Most studies analyzing malaria-temperature relations, including those investigating malaria risk and the possible impacts of climate change, are based solely on mean temperatures and extrapolate from functions determined under unrealistic laboratory conditions. Here, we present empirical evidence to show that, in addition to mean temperatures, daily fluctuations in temperature affect parasite infection, the rate of parasite development, and the essential elements of mosquito biology that combine to determine malaria transmission intensity. In general, we find that, compared with rates at equivalent constant mean temperatures, temperature fluctuation around low mean temperatures acts to speed up rate processes, whereas fluctuation around high mean temperatures acts to slow processes down. At the extremes (conditions representative of the fringes of malaria transmission, where range expansions or contractions will occur), fluctuation makes transmission possible at lower mean temperatures than currently predicted and can potentially block transmission at higher mean temperatures. If we are to optimize control efforts and develop appropriate adaptation or mitigation strategies for future climates, we need to incorporate into predictive models the effects of daily temperature variation and how that variation is altered by climate change.

Construction of a human corneal stromal equivalent with non-transfected human corneal stromal cells and acellular porcine corneal stromata.

PubMed

Diao, Jin-Mei; Pang, Xin; Qiu, Yue; Miao, Ying; Yu, Miao-Miao; Fan, Ting-Jun

2015-03-01

A tissue-engineered human corneal stroma (TE-HCS) has been developed as a promising equivalent to the native corneal stroma for replacement therapy. However, there is still a crucial need to improve the current approaches to render the TE-HCS equivalent more favorable for clinical applications. At the present study, we constructed a TE-HCS by incubating non-transfected human corneal stromal (HCS) cells in an acellular porcine corneal stromata (aPCS) scaffold in 20% fetal bovine serum supplemented DMEM/F12 (1:1) medium at 37 °C with 5% CO2in vitro. After 3 days of incubation, the constructed TE-HCS had a suitable tensile strength for transplantation, and a transparency that is comparable to native cornea. The TE-HCS had a normal histological structure which contained regularly aligned collagen fibers and differentiated HCS cells with positive expression of marker and functional proteins, mimicking a native HCS. After transplantation into rabbit models, the TE-HCS reconstructed normal corneal stroma in vivo and function well in maintaining corneal clarity and thickness, indicating that the completely biological TE-HCS could be used as a HCS equivalent. The constructed TE-HCS has promising potentials in regenerative medicine and treatment of diseases caused by corneal stromal disorders. Copyright © 2015 Elsevier Ltd. All rights reserved.

Relative Impact of Incorporating Pharmacokinetics on ...

EPA Pesticide Factsheets

The use of high-throughput in vitro assays has been proposed to play a significant role in the future of toxicity testing. In this study, rat hepatic metabolic clearance and plasma protein binding were measured for 59 ToxCast phase I chemicals. Computational in vitro-to-in vivo extrapolation was used to estimate the daily dose in a rat, called the oral equivalent dose, which would result in steady-state in vivo blood concentrations equivalent to the AC50 or lowest effective concentration (LEC) across more than 600 ToxCast phase I in vitro assays. Statistical classification analysis was performed using either oral equivalent doses or unadjusted AC50/LEC values for the in vitro assays to predict the in vivo effects of the 59 chemicals. Adjusting the in vitro assays for pharmacokinetics did not improve the ability to predict in vivo effects as either a discrete (yes or no) response or a low effect level (LEL) on a continuous dose scale. Interestingly, a comparison of the in vitro assay with the lowest oral equivalent dose with the in vivo endpoint with the lowest LEL suggested that the lowest oral equivalent dose may provide a conservative estimate of the point of departure for a chemical in a dose-response assessment. Furthermore, comparing the oral equivalent doses for the in vitro assays with the in vivo dose range that resulted in adverse effects identified more coincident in vitro assays across chemicals than expected by chance, suggesting that the approach ma

Grades, Student Satisfaction and Retention in Online and Face-to-Face Introductory Psychology Units: A Test of Equivalency Theory.

PubMed

Garratt-Reed, David; Roberts, Lynne D; Heritage, Brody

2016-01-01

There has been a recent rapid growth in the number of psychology courses offered online through institutions of higher education. The American Psychological Association has highlighted the importance of ensuring the effectiveness of online psychology courses (Halonen et al., 2013). Despite this, there have been inconsistent findings regarding student grades, satisfaction, and retention in online psychology units. Equivalency Theory (Simonson, 1999; Simonson et al., 1999) posits that online and classroom-based learners will attain equivalent learning outcomes when equivalent learning experiences are provided. We present a study of an online introductory psychology unit designed to provide equivalent learning experiences to the pre-existing face-to-face version of the unit. Using quasi-experimental methods, academic performance, student feedback, and retention data from 866 Australian undergraduate psychology students were examined to assess whether the online unit developed to provide equivalent learning experiences produced comparable outcomes to the 'traditional' unit delivered face-to-face. Student grades did not significantly differ between modes of delivery, except for a group-work based assessment where online students performed more poorly. Student satisfaction was generally high in both modes of the unit, with group-work the key source of dissatisfaction in the online unit. The results provide partial support for Equivalency Theory. The group-work based assessment did not provide an equivalent learning experience for students in the online unit highlighting the need for further research to determine effective methods of engaging students in online group activities. Consistent with previous research, retention rates were significantly lower in the online unit, indicating the need to develop effective strategies to increase online retention rates. While this study demonstrates successes in presenting students with an equivalent learning experience, we recommend that future research investigate means of successfully facilitating collaborative group-work assessment, and to explore contributing factors to actual student retention in online units beyond that of non-equivalent learning experiences.

Grades, Student Satisfaction and Retention in Online and Face-to-Face Introductory Psychology Units: A Test of Equivalency Theory

PubMed Central

Garratt-Reed, David; Roberts, Lynne D.; Heritage, Brody

2016-01-01

There has been a recent rapid growth in the number of psychology courses offered online through institutions of higher education. The American Psychological Association has highlighted the importance of ensuring the effectiveness of online psychology courses (Halonen et al., 2013). Despite this, there have been inconsistent findings regarding student grades, satisfaction, and retention in online psychology units. Equivalency Theory (Simonson, 1999; Simonson et al., 1999) posits that online and classroom-based learners will attain equivalent learning outcomes when equivalent learning experiences are provided. We present a study of an online introductory psychology unit designed to provide equivalent learning experiences to the pre-existing face-to-face version of the unit. Using quasi-experimental methods, academic performance, student feedback, and retention data from 866 Australian undergraduate psychology students were examined to assess whether the online unit developed to provide equivalent learning experiences produced comparable outcomes to the ‘traditional’ unit delivered face-to-face. Student grades did not significantly differ between modes of delivery, except for a group-work based assessment where online students performed more poorly. Student satisfaction was generally high in both modes of the unit, with group-work the key source of dissatisfaction in the online unit. The results provide partial support for Equivalency Theory. The group-work based assessment did not provide an equivalent learning experience for students in the online unit highlighting the need for further research to determine effective methods of engaging students in online group activities. Consistent with previous research, retention rates were significantly lower in the online unit, indicating the need to develop effective strategies to increase online retention rates. While this study demonstrates successes in presenting students with an equivalent learning experience, we recommend that future research investigate means of successfully facilitating collaborative group-work assessment, and to explore contributing factors to actual student retention in online units beyond that of non-equivalent learning experiences. PMID:27242587

The FLUKA Monte Carlo code coupled with the NIRS approach for clinical dose calculations in carbon ion therapy

NASA Astrophysics Data System (ADS)

Magro, G.; Dahle, T. J.; Molinelli, S.; Ciocca, M.; Fossati, P.; Ferrari, A.; Inaniwa, T.; Matsufuji, N.; Ytre-Hauge, K. S.; Mairani, A.

2017-05-01

Particle therapy facilities often require Monte Carlo (MC) simulations to overcome intrinsic limitations of analytical treatment planning systems (TPS) related to the description of the mixed radiation field and beam interaction with tissue inhomogeneities. Some of these uncertainties may affect the computation of effective dose distributions; therefore, particle therapy dedicated MC codes should provide both absorbed and biological doses. Two biophysical models are currently applied clinically in particle therapy: the local effect model (LEM) and the microdosimetric kinetic model (MKM). In this paper, we describe the coupling of the NIRS (National Institute for Radiological Sciences, Japan) clinical dose to the FLUKA MC code. We moved from the implementation of the model itself to its application in clinical cases, according to the NIRS approach, where a scaling factor is introduced to rescale the (carbon-equivalent) biological dose to a clinical dose level. A high level of agreement was found with published data by exploring a range of values for the MKM input parameters, while some differences were registered in forward recalculations of NIRS patient plans, mainly attributable to differences with the analytical TPS dose engine (taken as reference) in describing the mixed radiation field (lateral spread and fragmentation). We presented a tool which is being used at the Italian National Center for Oncological Hadrontherapy to support the comparison study between the NIRS clinical dose level and the LEM dose specification.

Colorectal cancer screening and prevention in women.

PubMed

Chacko, Lyssa; Macaron, Carole; Burke, Carol A

2015-03-01

Colorectal cancer (CRC) is one of the leading cancers and cause of cancer deaths in American women and men. Females and males share a similar lifetime cumulative risk of CRC however, substantial differences in risk factors, tumor biology, and effectiveness of cancer prevention services have been observed between them. This review distills the evidence documenting the unique variation observed between the genders relating to CRC risk factors, screening and prevention. Consistent evidence throughout the world demonstrates that women reach equivalent levels of adenomas and CRC as men but it occurs nearly a decade later in life than in their male counterparts. Women have a higher proportion of tumors which are hypermethylated, have microsatellite instability and located in the proximal colon suggesting the serrated pathway may be of greater consequence in them than in men. Other CRC risk factors such as smoking, diet and obesity have been shown to have disparate effects on women which may related to interactions between estrogen exposure, body fat distribution, and the biologic underpinnings of their tumors. There is data showing the uptake, choice, and efficacy of different CRC screening methods in women is dissimilar to that in men. The mortality benefit from FOBT, sigmoidoscopy, and protection from interval CRC by colonoscopy appears to be lower in women than men. A greater understanding of these gender idiosyncrasies will facilitate an personalized approach to CRC prevention and should ultimately lead to a reduced burden of disease.

Biological Activities of the Essential Oil from Erigeron floribundus.

PubMed

Petrelli, Riccardo; Orsomando, Giuseppe; Sorci, Leonardo; Maggi, Filippo; Ranjbarian, Farahnaz; Biapa Nya, Prosper C; Petrelli, Dezemona; Vitali, Luca A; Lupidi, Giulio; Quassinti, Luana; Bramucci, Massimo; Hofer, Anders; Cappellacci, Loredana

2016-08-13

Erigeron floribundus (Asteraceae) is an herbaceous plant widely used in Cameroonian traditional medicine to treat various diseases of microbial and non-microbial origin. In the present study, we evaluated the in vitro biological activities displayed by the essential oil obtained from the aerial parts of E. floribundus, namely the antioxidant, antimicrobial and antiproliferative activities. Moreover, we investigated the inhibitory effects of E. floribundus essential oil on nicotinate mononucleotide adenylyltransferase (NadD), a promising new target for developing novel antibiotics, and Trypanosoma brucei, the protozoan parasite responsible for Human African trypanosomiasis. The essential oil composition was dominated by spathulenol (12.2%), caryophyllene oxide (12.4%) and limonene (8.8%). The E. floribundus oil showed a good activity against Staphylococcus aureus (inhibition zone diameter, IZD of 14 mm, minimum inhibitory concentration, MIC of 512 µg/mL). Interestingly, it inhibited the NadD enzyme from S. aureus (IC50 of 98 µg/mL), with no effects on mammalian orthologue enzymes. In addition, T. brucei proliferation was inhibited with IC50 values of 33.5 µg/mL with the essential oil and 5.6 µg/mL with the active component limonene. The essential oil exhibited strong cytotoxicity on HCT 116 colon carcinoma cells with an IC50 value of 14.89 µg/mL, and remarkable ferric reducing antioxidant power (tocopherol-equivalent antioxidant capacity, TEAC = 411.9 μmol·TE/g).

Determination of the polyphenolic content of a Capsicum annuum L. extract by liquid chromatography coupled to photodiode array and mass spectrometry detection and evaluation of its biological activity.

PubMed

Mokhtar, Meriem; Soukup, Jan; Donato, Paola; Cacciola, Francesco; Dugo, Paola; Riazi, Ali; Jandera, Pavel; Mondello, Luigi

2015-01-01

The present study was aimed to investigate the polyphenolic profile of a pepper (Capsicum annuum L.) extract from Algeria and evaluate its biological activity. The total polyphenol content of the extract was determined as 1.373 mg of gallic acid equivalents (±0.0046), whereas the flavonoids were determined as 0.098 mg of quercetin (±0.0015). The determination of the complete polyphenolic profile of the extract was achieved by liquid chromatography with an RP-amide column in combination with photodiode array and mass spectrometry detection through an electrospray ionization interface. A total of 18 compounds were identified, of which five were reported for the first time in the sample tested. Quercetin rhamnoside was the most abundant compound (82.6 μg/g of fresh pepper) followed by quercetin glucoside (19.86 μg/g). The antioxidant activity and antimicrobial effects were also determined. For the antimicrobial tests assessed against Gram-positive and Gram-negative bacteria, kaempferol showed the strongest inhibitory effect followed by quercetin and caffeic acids. In the study of the cytotoxicity of the extract, the cancer cells (U937) were more affected than the normal cells (peripheral blood mononucleated cells), with more than 62% inhibition at the highest concentration. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A model for one-dimensional morphoelasticity and its application to fibroblast-populated collagen lattices.

PubMed

Menon, Shakti N; Hall, Cameron L; McCue, Scott W; McElwain, D L Sean

2017-10-01

The mechanical behaviour of solid biological tissues has long been described using models based on classical continuum mechanics. However, the classical continuum theories of elasticity and viscoelasticity cannot easily capture the continual remodelling and associated structural changes in biological tissues. Furthermore, models drawn from plasticity theory are difficult to apply and interpret in this context, where there is no equivalent of a yield stress or flow rule. In this work, we describe a novel one-dimensional mathematical model of tissue remodelling based on the multiplicative decomposition of the deformation gradient. We express the mechanical effects of remodelling as an evolution equation for the effective strain, a measure of the difference between the current state and a hypothetical mechanically relaxed state of the tissue. This morphoelastic model combines the simplicity and interpretability of classical viscoelastic models with the versatility of plasticity theory. A novel feature of our model is that while most models describe growth as a continuous quantity, here we begin with discrete cells and develop a continuum representation of lattice remodelling based on an appropriate limit of the behaviour of discrete cells. To demonstrate the utility of our approach, we use this framework to capture qualitative aspects of the continual remodelling observed in fibroblast-populated collagen lattices, in particular its contraction and its subsequent sudden re-expansion when remodelling is interrupted.

Fish assemblage responses to water withdrawals and water supply reservoirs in Piedmont streams

USGS Publications Warehouse

Freeman, Mary C.; Marcinek, P.A.

2006-01-01

Understanding effects of flow alteration on stream biota is essential to developing ecologically sustainable water supply strategies. We evaluated effects of altering flows via surface water withdrawals and instream reservoirs on stream fish assemblages, and compared effects with other hypothesized drivers of species richness and assemblage composition. We sampled fishes during three years in 28 streams used for municipal water supply in the Piedmont region of Georgia, U.S.A. Study sites had permitted average withdrawal rates that ranged from 13 times the stream?s seven-day, ten-year recurrence low flow (7Q10), and were located directly downstream either from a water supply reservoir or from a withdrawal taken from an unimpounded stream. Ordination analysis of catch data showed a shift in assemblage composition at reservoir sites corresponding to dominance by habitat generalist species. Richness of fluvial specialists averaged about 3 fewer species downstream from reservoirs, and also declined as permitted withdrawal rate increased above about 0.5 to one 7Q10-equivalent of water. Reservoir presence and withdrawal rate, along with drainage area, accounted for 70% of the among-site variance in fluvial specialist richness and were better predictor variables than percent of the catchment in urban land use or average streambed sediment size. Increasing withdrawal rate also increased the odds that a site?s Index of Biotic Integrity score fell below a regulatory threshold indicating biological impairment. Estimates of reservoir and withdrawal effects on stream biota could be used in predictive landscape models to support adaptive water supply planning intended to meet societal needs while conserving biological resources.

Cost-effectiveness analysis of intracameral cefuroxime use for prophylaxis of endophthalmitis after cataract surgery.

PubMed

Sharifi, Emile; Porco, Travis C; Naseri, Ayman

2009-10-01

To evaluate the cost-effectiveness of intracameral cefuroxime for postoperative endophthalmitis prophylaxis, and to determine the efficacy threshold necessary for alternative antibiotics to attain cost-effective equivalence with intracameral cefuroxime. Cost-effectiveness analysis. We study a hypothetical cohort of 100,000 patients undergoing cataract surgery as a part of the cost analysis. A cost-effectiveness model was constructed to analyze different antibiotic prophylactic regimens for postoperative endophthalmitis with intracameral cefuroxime as our base case. Efficacy was defined as the absolute reduction in rate of infection from background rate of infection, which was sourced from the literature. Antibiotic cost data were derived from the Red Book 2007 edition, and salary data were taken from the United States Bureau of Labor Statistics. Multivariate sensitivity analysis assessed the performance of antibiotic options under different scenarios. Cost per case of endophthalmitis prevented; theoretical maximal cost-effectiveness; efficacy threshold necessary to achieve cost-effective equivalence with intracameral cefuroxime; ratio indicating how many times more effective or less expensive alternative antibiotics would have to be to achieve cost-effective equivalence with intracameral cefuroxime. The cost-effectiveness ratio for intracameral cefuroxime is $1403 per case of postoperative endophthalmitis prevented. By comparison, the least expensive topical fluoroquinolone in our study, ciprofloxacin, would have to be >8 times more effective than intracameral cefuroxime to achieve cost-effective equivalence. The most expensive topical fluoroquinolones studied, gatifloxacin and moxifloxacin, would have to be > or =19 times more effective than intracameral cefuroxime to achieve cost-effective equivalence. A sensitivity analysis reveals that even in the worst case scenario for intracameral cefuroxime efficacy and with a 50% reduction in the cost of 4th-generation fluoroquinolones, gatifloxacin and moxifloxacin would have to be > or =9 times more effective than intracameral cefuroxime to achieve cost-effective equivalence. Administration of intracameral cefuroxime is relatively cost-effective in preventing endophthalmitis after cataract surgery. Owing to their high costs, many commonly used topical antibiotics are not cost-effective compared with intracameral cefuroxime, even under optimistic assumptions about their efficacy.

Silicon Supplementation Alters the Composition of Herbivore Induced Plant Volatiles and Enhances Attraction of Parasitoids to Infested Rice Plants.

PubMed

Liu, Jian; Zhu, Jiwei; Zhang, Pengjun; Han, Liwei; Reynolds, Olivia L; Zeng, Rensen; Wu, Jinhong; Shao, Yue; You, Minsheng; Gurr, Geoff M

2017-01-01

Silicon (Si) is important in plant defenses that operate in a direct manner against herbivores, and work in rice ( Oryza sativa ) has established that this is mediated by the jasmonate signaling pathway. Plant defenses also operate indirectly, by the production of herbivore induced plant volatiles (HIPVs) that attract predators and parasitoids of herbivores. These indirect defenses too are mediated by the jasmonate pathway but no earlier work has demonstrated an effect of Si on HIPVs. In this study, we tested the effect of Si supplementation versus Si deprivation to rice plants on subsequent HIPV production following feeding by the important pest, rice leaffolder ( Cnaphalocrocis medinalis ). Gas chromatography-mass spectrometry analyses showed lower production of α-bergamotene, β-sesquiohellandrene, hexanal 2-ethyl, and cedrol from +Si herbivore-infested plants compared with -Si infested plants. These changes in plant chemistry were ecologically significant in altering the extent to which parasitoids were attracted to infested plants. Adult females of Trathala flavo-orbitalis and Microplitis mediator both exhibited greater attraction to the HIPV blend of +Si plants infested with their respective insect hosts compared to -Si infested plants. In equivalent studies using RNAi rice plants in which jasmonate perception was silenced there was no equivalent change to the HIPV blend associated with Si treatment; indicating that the effects of Si on HIPVs are modulated by the jasmonate pathway. Further, this work demonstrates that silicon alters the HIPV blend of herbivore-infested rice plants. The significance of this finding is that there are no earlier-published studies of this phenomenon in rice or any other plant species. Si treatment to crops offers scope for enhancing induced, indirect defenses and associated biological control of pests because parasitoids are more strongly attracted by the HIPVs produced by +Si plants.

Evaluation of the immunological and hematological effects of chronic exposure of adult Peromyscus leucopus to Aroclor 1254 at concentrations equivalent to those at contaminated sites

USGS Publications Warehouse

Arena, S.R.; Segre, M.; French, J.B.

2000-01-01

Polychlorinated biphenyls are known to cause adverse health effects to biological systems; however, limited data is available on their effects on the immune system of wild species. Previous work by our lab found that 4 and 6-week old white-footed mice (Perornyscus leucopus) born from dams injected with a single dose (300 mg/kg) of Aroclor 1254, had altered immunological, hematological, and biochemical responses. The present study examines various immunological parameters of 22-week old white footed mice born from dams chronically exposed to Aroclor 1254 at concentrations equivalent to those at contaminated sites. Females were fed diets containing either Aroclor 1254 in corn oil or corn off only, for 3 months, then bred; pups were maintained on the same diets as their mothers. At 22 weeks of age, 31 of the young Peromyscus were analyzed. Body and organ weights were taken and immune function was evaluated by assessing blood profiles, cellularity of thymus and spleen, antibody response to the antigen DNP-KLH, and the in vitro proliferative response to the T-cell mitogen Conconavalin A (Con A). Liver weights and liver to body weight ratios in the treated mice were significantly higher compared to controls, while the combined weights of the adrenal glands were significantly lower. In addition, the number of thymocytes in the treated mice was significantly lower than that of the controls; however, thymocytes of treated mice had a higher degree of proliferation to Con A. Taken together, these results and those obtained from our previous study, indicate that monitoring of vulnerable immunological parameters in white-footed mice may be a useful indicator of exposure.

Clinical efficacy and mechanism of bilayered living human skin equivalent (HSE) in treatment of diabetic foot ulcers.

PubMed

Brem, Harold; Young, Jan; Tomic-Canic, Marjana; Isaacs, Cary; Ehrlich, H Paul

2003-01-01

Bilayered living human skin equivalent (HSE) consists of cultured keratinocytes residing on the surface of a fibroblast-populated collagen lattice. Although HSE is FDA-approved for treatment of diabetic foot and venous stasis ulcers, its clinical efficacy remains limited, because the molecular mechanisms underlying its therapeutic effect are not fully understood. It is, therefore, often applied mistakenly as a skin graft. In this report, we delineate a mechanism of HSE biological effect and consequent optimal clinical use in accelerating closure of diabetic foot ulcers. HSE was grafted onto nude mice and the release of various growth factors was evaluated by reverse transcription-polymerase chain reaction (RT-PCR) and immunochemistry. Clinical: HSE was grafted onto 11 consecutive patients with diabetes who had 13 non-ischemic foot ulcers and healing was measured as time to 100% closure (e.g., no drainage and 100% epithelialized). HSE cellular components were determined to express 15 different growth factors/cytokine genes known to promote wound healing. Histological evidence from the nude mice showed that the collagen component of HSE underwent remodeling within the first seven days of grafting. Clinical: All diabetic foot ulcers healed in 31.8 12.4 days. Local release of a unique combination of 15 growth factors expressed by HSE keratinocyte and fibroblast components generates closure of diabetic foot ulcers. HSE should be applied with the same surgical conditions for a skin graft (i.e., no cellulitis, no drainage, and negligible bacteria). We hypothesize that bilayered HSE generates its effect by way of the local synthesis and release of multiple growth factors in specific combination and concentration, which improves the impaired reparative process of chronic wounds.

Derivation of mean dose tolerances for new fractionation schemes and treatment modalities

NASA Astrophysics Data System (ADS)

Perkó, Zoltán; Bortfeld, Thomas; Hong, Theodore; Wolfgang, John; Unkelbach, Jan

2018-02-01

Avoiding toxicities in radiotherapy requires the knowledge of tolerable organ doses. For new, experimental fractionation schemes (e.g. hypofractionation) these are typically derived from traditional schedules using the biologically effective dose (BED) model. In this report we investigate the difficulties of establishing mean dose tolerances that arise since the mean BED depends on the entire spatial dose distribution, rather than on the dose level alone. A formula has been derived to establish mean physical dose constraints such that they are mean BED equivalent to a reference treatment scheme. This formula constitutes a modified BED equation where the influence of the spatial dose distribution is summarized in a single parameter, the dose shape factor. To quantify effects we analyzed 24 liver cancer patients for whom both proton and photon IMRT treatment plans were available. The results show that the standard BED equation—neglecting the spatial dose distribution—can overestimate mean dose tolerances for hypofractionated treatments by up to 20%. The shape difference between photon and proton dose distributions can cause 30-40% differences in mean physical dose for plans having identical mean BEDs. Converting hypofractionated, 5/15-fraction proton doses to mean BED equivalent photon doses in traditional 35-fraction regimens resulted in up to 10 Gy higher doses than applying the standard BED formula. The dose shape effect should be accounted for to avoid overestimation of mean dose tolerances, particularly when estimating constraints for hypofractionated regimens. Additionally, tolerances established for one treatment modality cannot necessarily be applied to other modalities with drastically different dose distributions, such as proton therapy. Last, protons may only allow marginal (5-10%) dose escalation if a fraction-size adjusted organ mean dose is constraining instead of a physical dose.

Modeling and simulation of biological systems using SPICE language

PubMed Central

Lallement, Christophe; Haiech, Jacques

2017-01-01

The article deals with BB-SPICE (SPICE for Biochemical and Biological Systems), an extension of the famous Simulation Program with Integrated Circuit Emphasis (SPICE). BB-SPICE environment is composed of three modules: a new textual and compact description formalism for biological systems, a converter that handles this description and generates the SPICE netlist of the equivalent electronic circuit and NGSPICE which is an open-source SPICE simulator. In addition, the environment provides back and forth interfaces with SBML (System Biology Markup Language), a very common description language used in systems biology. BB-SPICE has been developed in order to bridge the gap between the simulation of biological systems on the one hand and electronics circuits on the other hand. Thus, it is suitable for applications at the interface between both domains, such as development of design tools for synthetic biology and for the virtual prototyping of biosensors and lab-on-chip. Simulation results obtained with BB-SPICE and COPASI (an open-source software used for the simulation of biochemical systems) have been compared on a benchmark of models commonly used in systems biology. Results are in accordance from a quantitative viewpoint but BB-SPICE outclasses COPASI by 1 to 3 orders of magnitude regarding the computation time. Moreover, as our software is based on NGSPICE, it could take profit of incoming updates such as the GPU implementation, of the coupling with powerful analysis and verification tools or of the integration in design automation tools (synthetic biology). PMID:28787027

Current situations and discussions in Japan in relation to the new occupational equivalent dose limit for the lens of the eye.

PubMed

Yokoyama, Sumi; Hamada, Nobuyuki; Hayashida, Toshiyuki; Tsujimura, Norio; Tatsuzaki, Hideo; Kurosawa, Tadahiro; Nabatame, Kuniaki; Ohguchi, Hiroyuki; Ohno, Kazuko; Yamauchi-Kawaura, Chiyo; Iimoto, Takeshi; Ichiji, Takeshi; Hotta, Yutaka; Iwai, Satoshi; Akahane, Keiichi

2017-09-25

Since the International Commission on Radiological Protection recommended reducing the occupational equivalent dose limit for the lens of the eye in 2011, there have been extensive discussions in various countries. This paper reviews the current situation in radiation protection of the ocular lens and the discussions on the potential impact of the new lens dose limit in Japan. Topics include historical changes to the lens dose limit, the current situation with occupational lens exposures (e.g., in medical workers, nuclear workers, and Fukushima nuclear power plant workers) and measurements, and the current status of biological studies and epidemiological studies on radiation cataracts. Our focus is on the situation in Japan, but we believe such information sharing will be useful in many other countries.

Recovery and concentration of antioxidants from winery wastes.

PubMed

Soto, María Luisa; Conde, Enma; González-López, Noelia; Conde, María Jesús; Moure, Andrés; Sineiro, Jorge; Falqué, Elena; Domínguez, Herminia; Núñez, María José; Parajó, Juan Carlos

2012-03-09

Grape and wine byproducts have been extensively studied for the recovery of phenolic compounds with antioxidant activity and a variety of biological actions. The selective recovery and concentration of the phenolic compounds from the liquid phase separated from further diluted winery wastes has been proposed. Adsorption onto non ionic polymeric resins and further desorption with ethanolic solutions was studied. Several commercial food grade resins were screened with the aim of selecting the most suited for the practical recovery of phenolic compounds with radical scavenging activity. Under the optimized desorption conditions (using Sepabeads SP207 or Diaion HP20 as adsorbents and eluting with 96% ethanol at 50 °C) a powdered yellow-light brown product with 50% phenolic content, expressed as gallic acid equivalents, was obtained. The radical scavenging capacity of one gram of product was equivalent to 2-3 g of Trolox.

Scattering properties of normal and cancerous tissues from human stomach based on phase-contrast microscope

NASA Astrophysics Data System (ADS)

Zhang, Hui; Li, Zhifang; Li, Hui

2012-12-01

In order to study scattering properties of normal and cancerous tissues from human stomach, we collect images for human gastric specimens by using phase-contrast microscope. The images were processed by the way of mathematics morphology. The equivalent particle size distribution of tissues can be obtained. Combining with Mie scattering theory, the scattering properties of tissues can be calculated. Assume scattering of light in biological tissue can be seen as separate scattering events by different particles, total scattering properties can be equivalent to as scattering sum of particles with different diameters. The results suggest that scattering coefficient of the cancerous tissue is significantly higher than that of normal tissue. The scattering phase function is different especially in the backscattering area. Those are significant clinical benefits to diagnosis cancerous tissue

UV photofunctionalization promotes nano-biomimetic apatite deposition on titanium

PubMed Central

Saita, Makiko; Ikeda, Takayuki; Yamada, Masahiro; Kimoto, Katsuhiko; Lee, Masaichi Chang-Il; Ogawa, Takahiro

2016-01-01

Background Although biomimetic apatite coating is a promising way to provide titanium with osteoconductivity, the efficiency and quality of deposition is often poor. Most titanium implants have microscale surface morphology, and an addition of nanoscale features while preserving the micromorphology may provide further biological benefit. Here, we examined the effect of ultraviolet (UV) light treatment of titanium, or photofunctionalization, on the efficacy of biomimetic apatite deposition on titanium and its biological capability. Methods and results Micro-roughed titanium disks were prepared by acid-etching with sulfuric acid. Micro-roughened disks with or without photofunctionalization (20-minute exposure to UV light) were immersed in simulated body fluid (SBF) for 1 or 5 days. Photofunctionalized titanium disks were superhydrophilic and did not form surface air bubbles when immersed in SBF, whereas non-photofunctionalized disks were hydrophobic and largely covered with air bubbles during immersion. An apatite-related signal was observed by X-ray diffraction on photofunctionalized titanium after 1 day of SBF immersion, which was equivalent to the one observed after 5 days of immersion of control titanium. Scanning electron microscopy revealed nodular apatite deposition in the valleys and at the inclines of micro-roughened structures without affecting the existing micro-configuration. Micro-roughened titanium and apatite-deposited titanium surfaces had similar roughness values. The attachment, spreading, settling, proliferation, and alkaline phosphate activity of bone marrow-derived osteoblasts were promoted on apatite-coated titanium with photofunctionalization. Conclusion UV-photofunctionalization of titanium enabled faster deposition of nanoscale biomimetic apatite, resulting in the improved biological capability compared to the similarly prepared apatite-deposited titanium without photofunctionalization. Photofunctionalization-assisted biomimetic apatite deposition may be a novel method to effectively enhance micro-roughened titanium surfaces without altering their microscale morphology. PMID:26834469

Antibacterial, Antiradical Potential and Phenolic Compounds of Thirty-One Polish Mushrooms

PubMed Central

Los, Renata; Malm, Anna

2015-01-01

Background Among many sources of natural bioactive substances, mushrooms constitute a huge and almost unexplored group. Fungal compounds have been repeatedly reported to exert biological effects which have prompted their use in pharmaceutical and cosmetic industry. Therefore, the aim of this study was analysis of chemical composition and biological activity of 31 wild growing mushroom species (including saprophytic and parasitic) from Poland. Methods Qualitative and quantitative LC-ESI-MS/MS analysis of fourteen phenolic acids in the mushrooms analysed was performed. Moreover, total phenolic content was determined by the modified Folin-Ciocalteau method. Antioxidative activity of ethanolic extracts towards DPPH• free radical was examined. Antibacterial activity against Gram-positive (S. epidermidis, S. aureus, B. subtilis, M. luteus) and Gram-negative (E. coli, K. pneumoniae, P. aeruginosa, P. mirabilis) microbial strains was analyzed. Results As a result, the first such broad report on polyphenolic composition, antiradical and antimicrobial potential of wild growing Polish mushrooms was developed. Mushroom extracts were found to contain both benzoic (protocatechuic, 4-OH-benzoic, vanillic, syringic) and cinnamic acid derivatives (caffeic, p-coumaric, ferulic). Total phenolic content in mushrooms ranged between 2.79 and 53.13 mg gallic acid equivalent /g of dried extract in Trichaptum fuscoviolaceum and Fomes fomentarius, respectively. Fungi showed much differentiated antiradical activity, from highly active F. fomentarius to poorly effective Russula fragilis (IC50 1.39 to 120.54 mg per mg DPPH•, respectively). A quite considerable relationship between phenolic content and antiradical activity has been demonstrated. Mushrooms varied widely in antimicrobial potential (MIC from 0.156 to 5 mg/ml). Generally, a slightly higher activity against Gram-positive than Gram-negative strains was observed. This is the first study concerning the chemical composition and biological activity of the majority of investigated species. PMID:26468946

Diaper area skin microflora of normal children and children with atopic dermatitis.

PubMed Central

Keswick, B H; Seymour, J L; Milligan, M C

1987-01-01

In vitro studies established that neither cloth nor disposable diapers demonstrably contributed to the growth of Escherichia coli, Proteus vulgaris, Staphylococcus aureus, or Candida albicans when urine was present as a growth medium. In a clinical study of 166 children, the microbial skin flora of children with atopic dermatitis was compared with the flora of children with normal skin to determine the influence of diaper type. No biologically significant differences were detected between groups wearing disposable or cloth diapers in terms of frequency of isolation or log mean recovery of selected skin flora. Repeated isolation of S. aureus correlated with atopic dermatitis. The log mean recovery of S. aureus was higher in the atopic groups. The effects of each diaper type on skin microflora were equivalent in the normal and atopic populations. PMID:3546360

The CDRH helix. A phase I clinical trial.

PubMed

Shimm, D S; Cetas, T C; Hynynen, K H; Buechler, D N; Anhalt, D P; Sykes, H F; Cassady, J R

1989-04-01

Seventeen patients have been given regional hyperthermia treatments using the Center for Devices and Radiologic Health (CDRH) Helix, a resonant helical coil unit. Most of these patients had large, clinically advanced tumors, whose mean volume exceeded 1000 cc. Mean maximum, minimum, and average temperatures were 40.6, 38.6, and 39.6 degrees C, respectively, for all sites combined. The pelvic heating capabilities of the CDRH Helix and the BSD-1000 annular phased array were compared, and generally were equivalent. Although the Helix could be used in a wider variety of locations, and was more comfortable and easier to use than the BSD-1000 annular phased array, neither device was particularly effective in generating clinically useful temperatures; the Helix is currently under investigation for use in regional-systemic hyperthermia in combination with antineoplastic drugs and biologic response modifiers.

Implementation of an Analytical Model for Leakage Neutron Equivalent Dose in a Proton Radiotherapy Planning System

PubMed Central

Eley, John; Newhauser, Wayne; Homann, Kenneth; Howell, Rebecca; Schneider, Christopher; Durante, Marco; Bert, Christoph

2015-01-01

Equivalent dose from neutrons produced during proton radiotherapy increases the predicted risk of radiogenic late effects. However, out-of-field neutron dose is not taken into account by commercial proton radiotherapy treatment planning systems. The purpose of this study was to demonstrate the feasibility of implementing an analytical model to calculate leakage neutron equivalent dose in a treatment planning system. Passive scattering proton treatment plans were created for a water phantom and for a patient. For both the phantom and patient, the neutron equivalent doses were small but non-negligible and extended far beyond the therapeutic field. The time required for neutron equivalent dose calculation was 1.6 times longer than that required for proton dose calculation, with a total calculation time of less than 1 h on one processor for both treatment plans. Our results demonstrate that it is feasible to predict neutron equivalent dose distributions using an analytical dose algorithm for individual patients with irregular surfaces and internal tissue heterogeneities. Eventually, personalized estimates of neutron equivalent dose to organs far from the treatment field may guide clinicians to create treatment plans that reduce the risk of late effects. PMID:25768061

Implementation of an analytical model for leakage neutron equivalent dose in a proton radiotherapy planning system.

PubMed

Eley, John; Newhauser, Wayne; Homann, Kenneth; Howell, Rebecca; Schneider, Christopher; Durante, Marco; Bert, Christoph

2015-03-11

Equivalent dose from neutrons produced during proton radiotherapy increases the predicted risk of radiogenic late effects. However, out-of-field neutron dose is not taken into account by commercial proton radiotherapy treatment planning systems. The purpose of this study was to demonstrate the feasibility of implementing an analytical model to calculate leakage neutron equivalent dose in a treatment planning system. Passive scattering proton treatment plans were created for a water phantom and for a patient. For both the phantom and patient, the neutron equivalent doses were small but non-negligible and extended far beyond the therapeutic field. The time required for neutron equivalent dose calculation was 1.6 times longer than that required for proton dose calculation, with a total calculation time of less than 1 h on one processor for both treatment plans. Our results demonstrate that it is feasible to predict neutron equivalent dose distributions using an analytical dose algorithm for individual patients with irregular surfaces and internal tissue heterogeneities. Eventually, personalized estimates of neutron equivalent dose to organs far from the treatment field may guide clinicians to create treatment plans that reduce the risk of late effects.

10 CFR 835.203 - Combining internal and external equivalent doses.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 4 2010-01-01 2010-01-01 false Combining internal and external equivalent doses. 835.203 Section 835.203 Energy DEPARTMENT OF ENERGY OCCUPATIONAL RADIATION PROTECTION Standards for Internal and External Exposure § 835.203 Combining internal and external equivalent doses. (a) The total effective dose...

5 CFR 300.605 - Creditable service.

Code of Federal Regulations, 2011 CFR

2011-01-01

... effect when the non-GS service was performed. The equivalent GS grade is the GS grade with a... higher grade (or equivalent) in positions to which appointed in the Federal civilian service is... General Schedule (GS) is credited at the equivalent GS grade by comparing the candidate's rate of basic...

5 CFR 300.605 - Creditable service.

Code of Federal Regulations, 2013 CFR

2013-01-01

... effect when the non-GS service was performed. The equivalent GS grade is the GS grade with a... higher grade (or equivalent) in positions to which appointed in the Federal civilian service is... General Schedule (GS) is credited at the equivalent GS grade by comparing the candidate's rate of basic...

5 CFR 300.605 - Creditable service.

Code of Federal Regulations, 2010 CFR

2010-01-01

... effect when the non-GS service was performed. The equivalent GS grade is the GS grade with a... higher grade (or equivalent) in positions to which appointed in the Federal civilian service is... General Schedule (GS) is credited at the equivalent GS grade by comparing the candidate's rate of basic...

5 CFR 300.605 - Creditable service.

Code of Federal Regulations, 2012 CFR

2012-01-01

... effect when the non-GS service was performed. The equivalent GS grade is the GS grade with a... higher grade (or equivalent) in positions to which appointed in the Federal civilian service is... General Schedule (GS) is credited at the equivalent GS grade by comparing the candidate's rate of basic...

40 CFR 403.12 - Reporting requirements for POTW's and industrial users.

Code of Federal Regulations, 2014 CFR

2014-07-01

... Industrial Users subject to equivalent mass or concentration limits established by the Control Authority in... for the duration of the effective period of the Permit or other equivalent individual control... Industrial Users subject to equivalent mass or concentration limits established by the Control Authority in...

42 CFR 440.320 - State plan requirements: Optional enrollment for exempt individuals.

Code of Federal Regulations, 2010 CFR

2010-10-01

... benchmark or benchmark-equivalent benefit package, the State must effectively inform the individual prior to...-equivalent benefit package and the costs under such a package and provide a comparison of how they differ... benchmark-equivalent benefit package. (4) For individuals who the State determines have become exempt...

42 CFR 440.320 - State plan requirements: Optional enrollment for exempt individuals.

Code of Federal Regulations, 2011 CFR

2011-10-01

... benchmark or benchmark-equivalent benefit package, the State must effectively inform the individual prior to...-equivalent benefit package and the costs under such a package and provide a comparison of how they differ... benchmark-equivalent benefit package. (4) For individuals who the State determines have become exempt...

42 CFR 440.320 - State plan requirements: Optional enrollment for exempt individuals.

Code of Federal Regulations, 2012 CFR

2012-10-01

... benchmark or benchmark-equivalent benefit package, the State must effectively inform the individual prior to...-equivalent benefit package and the costs under such a package and provide a comparison of how they differ... benchmark-equivalent benefit package. (4) For individuals who the State determines have become exempt...

42 CFR 440.320 - State plan requirements: Optional enrollment for exempt individuals.

Code of Federal Regulations, 2013 CFR

2013-10-01

... benchmark or benchmark-equivalent benefit package, the State must effectively inform the individual prior to...-equivalent benefit package and the costs under such a package and provide a comparison of how they differ... benchmark-equivalent benefit package. (4) For individuals who the State determines have become exempt...

42 CFR 440.320 - State plan requirements: Optional enrollment for exempt individuals.

Code of Federal Regulations, 2014 CFR

2014-10-01

... benchmark or benchmark-equivalent benefit package, the State must effectively inform the individual prior to...-equivalent benefit package and the costs under such a package and provide a comparison of how they differ... benchmark-equivalent benefit package. (4) For individuals who the State determines have become exempt...

Whatever Gave You That Idea? False Memories Following Equivalence Training: A Behavioral Account of the Misinformation Effect

PubMed Central

Challies, Danna M; Hunt, Maree; Garry, Maryanne; Harper, David N

2011-01-01

The misinformation effect is a term used in the cognitive psychological literature to describe both experimental and real-world instances in which misleading information is incorporated into an account of an historical event. In many real-world situations, it is not possible to identify a distinct source of misinformation, and it appears that the witness may have inferred a false memory by integrating information from a variety of sources. In a stimulus equivalence task, a small number of trained relations between some members of a class of arbitrary stimuli result in a large number of untrained, or emergent relations, between all members of the class. Misleading information was introduced into a simple memory task between a learning phase and a recognition test by means of a match-to-sample stimulus equivalence task that included both stimuli from the original learning task and novel stimuli. At the recognition test, participants given equivalence training were more likely to misidentify patterns than those who were not given such training. The misinformation effect was distinct from the effects of prior stimulus exposure, or partial stimulus control. In summary, stimulus equivalence processes may underlie some real-world manifestations of the misinformation effect. PMID:22084495

Dual-fuel production from restaurant grease trap waste: bio-fuel oil extraction and anaerobic methane production from the post-extracted residue.

PubMed

Kobayashi, Takuro; Kuramochi, Hidetoshi; Maeda, Kouji; Tsuji, Tomoya; Xu, Kaiqin

2014-10-01

An effective way for restaurant grease trap waste (GTW) treatment to generate fuel oil and methane by the combination of physiological and biological processes was investigated. The heat-driven extraction could provide a high purity oil equivalent to an A-grade fuel oil of Japanese industrial standard with 81-93 wt% of extraction efficiency. A post-extracted residue was treated as an anaerobic digestion feedstock, and however, an inhibitory effect of long chain fatty acid (LCFA) was still a barrier for high-rate digestion. From the semi-continuous experiment fed with the residual sludge as a single substrate, it can be concluded that the continuous addition of calcium into the reactor contributed to reducing LCFA inhibition, resulting in the long-term stable operation over one year. Furthermore, the anaerobic reactor performed well with 70-80% of COD reduction and methane productivity under an organic loading rate up to 5.3g-COD/L/d. Copyright © 2014 Elsevier Ltd. All rights reserved.

Study of zalema grape pomace: phenolic composition and biological effects in Caenorhabditis elegans.

PubMed

Jara-Palacios, M José; González-Manzano, Susana; Escudero-Gilete, M Luisa; Hernanz, Dolores; Dueñas, Montserrat; González-Paramás, Ana M; Heredia, Francisco J; Santos-Buelga, Celestino

2013-05-29

The phenolic composition of the extractable fraction of Zalema grape pomace has been analyzed by HPLC-DAD-MS and consisted of mainly flavanols and flavonols (122.75 and 23.11 mg/100 g dry pomace, respectively). The antioxidant activity has been determined by in vitro FRAP, ABTS, and ORAC assays (11.7, 34.9, and 63.6 mmol of Trolox equivalents (TE) per 100 g of dry pomace, respectively) and in vivo using the model organism Caenorhabditis elegans . Cultivation of C. elegans in media containing 100 μg/mL dry pomace extract increased the survival of worms submitted to thermally induced oxidative stress, whereas a decrease in the rate of worm survival was found for 300 μg/mL extract. Interestingly, the levels of reactive oxygen species (ROS) were significantly decreased in stressed worms treated with the pomace extract at the two concentration levels. Further studies are required to explain this unexpected behavior, as well as to determine the compounds and mechanisms involved in the observed effects.

Sidestream cigarette smoke toxicity increases with aging and exposure duration

PubMed Central

Schick, Suzaynn; Glantz, Stanton A

2006-01-01

Objectives To determine the effects of aging on the toxicity of sidestream tobacco smoke, the complex chemical mixture that enters the air from the lit end of burning cigarettes and constitutes the vast bulk of secondhand smoke. Design Statistical analysis of data from controlled experimental exposures of Sprague Dawley rats to fresh and aged (for more than 30 minutes) sidestream smoke for up to 90 days followed by histological sectioning of the respiratory epithelium. The data were obtained from a series of experiments conducted at Philip Morris' formerly secret INBIFO (Institut für Biologische Forschung) laboratory in Germany. Results Using total particulate material as the measure of smoke exposure, aging sidestream cigarette smoke for at least 30 minutes increases its toxicity fourfold for 21 day exposures and doubles the toxicity for 90 day exposures, relative to fresh sidestream smoke. Conclusions These results help explain the relatively large biological effects of secondhand smoke compared to equivalent mass doses of mainstream smoke. PMID:17130369

Apoptosis-inducing effects and growth inhibitory of a novel chalcone, in human hepatic cancer cells and lung cancer cells.

PubMed

Dong, Naiwei; Liu, Xin; Zhao, Tong; Wang, Lei; Li, Huimin; Zhang, Shuqian; Li, Xia; Bai, Xue; Zhang, Yong; Yang, Baofeng

2018-05-29

Apoptosis is an important biological phenomenon, which affects many diseases, such as cancer and Alzheimer's disease. In the present study, we observed that chalcone 9X, an aromatic ketone, induced apoptosis of human hepatic and lung cancer cells and inhibited cancer cell migration and invasion. This compound strongly suppressed the growth of tumor in a mouse model of xenograft tumors. The anticancer activity of chalcone 9X was equivalent to 5-fluorouracil (5-FU) as a positive control agent, whereas the toxic effect of chalcone 9X in non-cancer cells was weaker than 5-FU. Molecular docking results showed that chalcone 9X could act on the active sites of pro-apoptotic proteins capspases-3 and -8 to induce apoptotic death of cancer cells. Our findings suggest that chalcone 9X might be considered a candidate compound of novel anticancer drug in the future. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Effects of CO[sub 2] and climate change on forest trees: Soil biology and enzymology

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moldenke, A.R.; Baumeister, N.; Caldwell, B.A.

1994-06-01

Samples of Teracosm soils were analyzed shortly after initial setup to determine whether initial conditions were equivalent and matched expected values for local soils. Total and active fungal biomass, active bacterial biomass and protozoan numbers were reduced, with greatest decreases occurring in the A horizon. No effect was observed on total bacterial biomass, nematode or anthropod densities, but changes in nematode and arthropod species composition occurred. Significant differences in total density and species composition occurred between the enclosed Teracosms and the open controls. Arthropod and nematode community structure in the three altitudinal field sites had significantly diverged. No significant differencesmore » in activities of key soil enzymes in C- and N-cycling (acid phosphatase, protease, B-glucosidase, phenol oxidase and peroxidase) were found between initial samples relative to treatment, but all levels were significantly difference relative to depth in soil profile. Activities were within ranges previously observed in forests of the Pacific Northwest.« less

Evidence of recent climate change within the historic range of Rio Grande cutthroat trout: implications for management and future persistence

USGS Publications Warehouse

Zeigler, Matthew P.; Todd, Andrew S.; Caldwell, Colleen A.

2012-01-01

Evidence of anthropogenically influenced climate change has motivated natural resource managers to incorporate adaptive measures to minimize risks to sensitive and threatened species. Detecting trends in climate variables (i.e., air temperature and hydrology) can serve as a valuable management tool for protecting vulnerable species by increasing our understanding of localized conditions and trends. The Rio Grande cutthroat trout Oncorhynchus clarkii virginalis has suffered a severe decline in its historical distribution, with the majority of current populations persisting in isolated headwater streams. To evaluate recent climate change within the subspecies' historical range, we examined trends in average air temperatures, biologically important hydrological variables (timing of snowmelt and seasonal flows), and the April 1 snow water equivalent over the last 45 years (1963–2007). While rates of change in all three metrics were variable across sites, rangewide patterns were evident. Across the subspecies' historical range, average annual air temperatures increased (0.29°C per decade) and the timing of snowmelt shifted 10.6 d earlier in the year (2.3 d/decade). Flows increased during biologically important periods, including winter (January 1–March 31; 6.6% increase per decade), prespawning (April 1–May 14; 6.9% increase per decade), and spawning (May 15–June 15; 4.2% increase per decade) and decreased in summer (June 16–September 15; 1.9% decrease per decade). Evidence of decreasing April 1 snow water equivalent (5.3% per decade) was also observed. While the impacts of these changes at the population level are equivocal, it is likely that negative effects would influence the subspecies by altering its distribution, decreasing available habitat, and altering the timing of important life history components. Continued monitoring and proactive management will be required to increase the resiliency of remaining populations to ensure long-term persistence and protection in a changing climate.

Synthesizing Equivalence Indices for the Comparative Evaluation of Technoeconomic Efficiency of Industrial Processes at the Design/Re-engineering Level

NASA Astrophysics Data System (ADS)

Fotilas, P.; Batzias, A. F.

2007-12-01

The equivalence indices synthesized for the comparative evaluation of technoeconomic efficiency of industrial processes are of critical importance since they serve as both, (i) positive/analytic descriptors of the physicochemical nature of the process and (ii) measures of effectiveness, especially helpful for investigated competitiveness in the industrial/energy/environmental sector of the economy. In the present work, a new algorithmic procedure has been developed, which initially standardizes a real industrial process, then analyzes it as a compromise of two ideal processes, and finally synthesizes the index that can represent/reconstruct the real process as a result of the trade-off between the two ideal processes taking as parental prototypes. The same procedure makes fuzzy multicriteria ranking within a set of pre-selected industrial processes for two reasons: (a) to analyze the process most representative of the production/treatment under consideration, (b) to use the `second best' alternative as a dialectic pole in absence of the two ideal processes mentioned above. An implantation of this procedure is presented, concerning a facility of biological wastewater treatment with six alternatives: activated sludge through (i) continuous-flow incompletely-stirred tank reactors in series, (ii) a plug flow reactor with dispersion, (iii) an oxidation ditch, and biological processing through (iv) a trickling filter, (v) rotating contactors, (vi) shallow ponds. The criteria used for fuzzy (to count for uncertainty) ranking are capital cost, operating cost, environmental friendliness, reliability, flexibility, extendibility. Two complementary indices were synthesized for the (ii)-alternative ranked first and their quantitative expressions were derived, covering a variety of kinetic models as well as recycle/bypass conditions. Finally, analysis of estimating the optimal values of these indices at maximum technoeconomic efficiency is presented and the implications (expected to be) caused by exogenous and endogenous factors (e.g., environmental standards change and innovative energy savings/substitution, respectively) are discussed by means of marginal efficiency graphs.

Design and verification of large-moment transmitter loops for geophysical applications

NASA Astrophysics Data System (ADS)

Sternberg, Ben K.; Dvorak, Steven L.; Feng, Wanjie

2017-01-01

In this paper we discuss the modeling, design and verification of large-moment transmitter (TX) loops for geophysical applications. We first develop two equivalent circuit models for TX loops. We show that the equivalent inductance can be predicted using one of two empirical formulas. The stray capacitance of the loop is then calculated using the measured self-resonant frequency and the loop inductance. We model the losses associated with both the skin effect and the dissipation factor in both of these equivalent circuits. We find that the two equivalent circuit models produce the same results provided that the dissipation factor is small. Next we compare the measured input impedances for three TX loops that were constructed with different wire configurations with the equivalent circuit model. We found excellent agreement between the measured and simulated results after adjusting the dissipation factor. Since the skin effect and dissipation factor yield good agreement with measurements, the proximity effect is negligible in the three TX loops that we tested. We found that the effects of the dissipation factor dominated those of the skin effect when the wires were relatively close together. When the wires were widely separated, then the skin effect was the dominant loss mechanism. We also found that loops with wider wire separations exhibited higher self-resonant frequencies and better high-frequency performance.

Affordance Equivalences in Robotics: A Formalism

PubMed Central

Andries, Mihai; Chavez-Garcia, Ricardo Omar; Chatila, Raja; Giusti, Alessandro; Gambardella, Luca Maria

2018-01-01

Automatic knowledge grounding is still an open problem in cognitive robotics. Recent research in developmental robotics suggests that a robot's interaction with its environment is a valuable source for collecting such knowledge about the effects of robot's actions. A useful concept for this process is that of an affordance, defined as a relationship between an actor, an action performed by this actor, an object on which the action is performed, and the resulting effect. This paper proposes a formalism for defining and identifying affordance equivalence. By comparing the elements of two affordances, we can identify equivalences between affordances, and thus acquire grounded knowledge for the robot. This is useful when changes occur in the set of actions or objects available to the robot, allowing to find alternative paths to reach goals. In the experimental validation phase we verify if the recorded interaction data is coherent with the identified affordance equivalences. This is done by querying a Bayesian Network that serves as container for the collected interaction data, and verifying that both affordances considered equivalent yield the same effect with a high probability. PMID:29937724

Sound source identification and sound radiation modeling in a moving medium using the time-domain equivalent source method.

PubMed

Zhang, Xiao-Zheng; Bi, Chuan-Xing; Zhang, Yong-Bin; Xu, Liang

2015-05-01

Planar near-field acoustic holography has been successfully extended to reconstruct the sound field in a moving medium, however, the reconstructed field still contains the convection effect that might lead to the wrong identification of sound sources. In order to accurately identify sound sources in a moving medium, a time-domain equivalent source method is developed. In the method, the real source is replaced by a series of time-domain equivalent sources whose strengths are solved iteratively by utilizing the measured pressure and the known convective time-domain Green's function, and time averaging is used to reduce the instability in the iterative solving process. Since these solved equivalent source strengths are independent of the convection effect, they can be used not only to identify sound sources but also to model sound radiations in both moving and static media. Numerical simulations are performed to investigate the influence of noise on the solved equivalent source strengths and the effect of time averaging on reducing the instability, and to demonstrate the advantages of the proposed method on the source identification and sound radiation modeling.

Research on the equivalence between digital core and rock physics models

NASA Astrophysics Data System (ADS)

Yin, Xingyao; Zheng, Ying; Zong, Zhaoyun

2017-06-01

In this paper, we calculate the elastic modulus of 3D digital cores using the finite element method, systematically study the equivalence between the digital core model and various rock physics models, and carefully analyze the conditions of the equivalence relationships. The influences of the pore aspect ratio and consolidation coefficient on the equivalence relationships are also further refined. Theoretical analysis indicates that the finite element simulation based on the digital core is equivalent to the boundary theory and Gassmann model. For pure sandstones, effective medium theory models (SCA and DEM) and the digital core models are equivalent in cases when the pore aspect ratio is within a certain range, and dry frame models (Nur and Pride model) and the digital core model are equivalent in cases when the consolidation coefficient is a specific value. According to the equivalence relationships, the comparison of the elastic modulus results of the effective medium theory and digital rock physics is an effective approach for predicting the pore aspect ratio. Furthermore, the traditional digital core models with two components (pores and matrix) are extended to multiple minerals to more precisely characterize the features and mineral compositions of rocks in underground reservoirs. This paper studies the effects of shale content on the elastic modulus in shaly sandstones. When structural shale is present in the sandstone, the elastic modulus of the digital cores are in a reasonable agreement with the DEM model. However, when dispersed shale is present in the sandstone, the Hill model cannot describe the changes in the stiffness of the pore space precisely. Digital rock physics describes the rock features such as pore aspect ratio, consolidation coefficient and rock stiffness. Therefore, digital core technology can, to some extent, replace the theoretical rock physics models because the results are more accurate than those of the theoretical models.

Space Radiation Induced Cytogenetic Damage in the Blood Lymphocytes of Astronauts

NASA Technical Reports Server (NTRS)

George, K.; Cucinotta, F. A.

2008-01-01

Cytogenetic analysis of astronauts blood lymphocytes provides a direct in vivo measurement of space radiation damage, which takes into account individual radiosensitivity and considers the influence of microgravity and other stress conditions. We present our latest analyses of chromosome damage in astronauts blood lymphocytes assessed by fluorescence in situ hybridization (FISH) chromosome painting and collected at various times beginning directly after return from space to several years after flight. Dose was derived from frequencies of chromosome exchanges using preflight calibration curves, and the Relative Biological Effect (RBE) was estimated by comparison with individually measured physically absorbed doses. Values for average RBE were compared to the average quality factor (Q), from direct measurements of the lineal energy spectra using a tissue-equivalent proportional counter (TEPC) and radiation transport codes. Results prove that cytogenetic biodosimetry analyses on blood collected within a week or two of return from space provides a reliable estimate of equivalent radiation dose and risk after protracted exposure to space radiation of a few months or more. However, data collected several months or years after flight suggests that the yield of chromosome translocations may decline with time after the mission, indicating that retrospective doses may be more difficult to estimate. In addition, limited data on multiple flights show a lack of correlation between time in space and translocation yields. Data from one crewmember, who has participated in two separate long-duration space missions and has been followed up for over 10 years, provide limited information on the effect of repeat flights and show a possible adaptive response to space radiation exposure.

Effect of probiotic-fermented, genetically modified soy milk on hypercholesterolemia in hamsters.

PubMed

Tsai, Tsung-Yu; Chen, Li-Ying; Pan, Tzu-Ming

2014-02-01

The rapid progress of biotechnology and molecular biology has led to genetically modified (GM) crops becoming a part of agricultural production. There are concerns that the issues of the functional ingredients in GM products have not been addressed, such as the bioactivities of soy proteins and isoflavones. This study aimed to investigate the effects of probiotic-fermented GM soy milk on hypercholesterolemia, and atherosclerotic risks in hamsters. One hundred and twelve male Golden Syrian hamsters (Mesocricetus auratus) were randomly assigned into 14 groups of 8 animals each. Normal- and high-cholesterol experimental diets were supplemented with GM or non-GM soy milk with or without probiotic-fermentation for 8 weeks. Serum and fecal lipid levels were measured. Moreover, aortic plaque in artery were stained, and thiobarbituric acid reactive substance content, super oxide dismutase activity and caralase activity were determined. GM or non-GM soy milk with or without probiotic-fermentation significantly decreased (p < 0.05) serum TC levels, compared with a high-cholesterol diet group. TC levels in hamsters fed GM soy milk were not significantly different from TC levels in the non-GM soy milk group (p > 0.05). GM soy milk groups can reduce risk of developing atherosclerosis through lowered oxidative stress and reduced atherosclerotic plaque formation in the aorta, and are thus at least equivalent to non-GM soy milk. GM soy milk with or without probiotic-fermentation can improve hypercholesterolemia and reduce the risk of atherosclerosis, and is considered substantially equivalent to non-GM soy milk in terms of these bioactive functions. Copyright © 2012. Published by Elsevier B.V.

Creating beauty: creativity compensates for low physical attractiveness when individuals assess the attractiveness of social and romantic partners

PubMed Central

2017-01-01

Although creativity is attractive in a potential mate, it is unclear (i) whether the effects of creativity on attractiveness generalize to other social contexts and (ii) whether creativity has equivalent effects on men's and women's attractiveness. As social knowledge of creativity may either enhance or ‘offset’ the appeal of social partners who differ in physical attractiveness, three repeated measures experiments were conducted to directly address these issues. Here, participants rated a series of face–text pairs for attractiveness on trials that differed in one of four combinations of facial attractiveness (attractive and less attractive) and creativity (creative and less creative), rating story-tellers in two experiments (short interpretations of an identical painting) and creative ideas in a further experiment (alternative uses for an everyday object). Regardless of the sex of the judge, creativity and facial attractiveness had independent effects on men's overall attractiveness (initial experiment) and, in further experiments, more substantial effects on the attractiveness of men with less attractive faces than men with attractive faces (when using a different measure of creativity) and specific effects on the attractiveness of individuals with less attractive faces (when using different face stimuli). Collectively, across three experiments, these findings suggest that creativity may compensate for putative cues to lower biological ‘quality’ and that the benefits of creativity to social groups more generally enhance attraction to creative men (in two experiments) and creative men and women (one experiment). More broadly, the data suggest that species can integrate knowledge of cognitive intelligence with visual cues to biological ‘quality’ to facilitate mate and/or ally choice. PMID:28484614

EPA Region 1 Environmentally Sensitive Areas

EPA Pesticide Factsheets

This coverage represents polygon equivalents of environmentally sensitive areas (ESA) in EPA Region I. ESAs were developed as part of an EPA headquarters initiative based on reviews of various regulatory and guidance documents, as well as phone interviews with federal/state/local government agencies and private organizations. ESAs include, but are not limited to, wetlands, biological resources, habitats, national parks, archaeological/historic sites, natural heritage areas, tribal lands, drinking water intakes, marinas/boat ramps, wildlife areas, etc.

Habitat Equivalency Analysis: A Potential Tool for Estimating Environmental Benefits

DTIC Science & Technology

2008-01-01

of animal tissue produced per year. It is assumed that the dredged areas will be permanently taken out of production and recovery time for the...from the mine seriously contaminated 40 km (25 miles) of nearby Panther Creek, a tributary of the Salmon River. Water quality, benthic fauna, and...restore the biological health of Panther Creek. Trustees responsible for monitoring the cleanup determined that the abundance of Chinook salmon was

Frequency-Agile LIDAR Receiver for Chemical and Biological Agent Sensing

DTIC Science & Technology

2010-06-01

transimpedance preamplifier architecture was optimized around the selected IR detector diode – Input-referenced noise density of 0.8 nV/ Hz0.5  A portion of...objectives: • Reduce baseline (background) photon flux on detector : Tunable Fabry-Perot etalon in optical train • Reduce input-referenced amplifier noise ...custom amplifier • Reduce detector dark current: High impedance detector  Performance Metrics: – Noise equivalent power of receiver system (NEP

The Evolution of Cooperation in the Finitely Repeated Prisoner’s Dilemma

DTIC Science & Technology

1989-09-01

biological evolutionary game theory, mathematical ecology (the replicator dynamics are formally equivalent to the Lotka - Volterra dynamics), and...repeated prisoner’s dilemma. Under the dynamics considered, if there is convergence to a limit (in general there need not be), then that limit must...of time. It will be noted also that this same behavior can create computation problems making it imprudent in general to try to infer limiting

[The human life cycle from a theoretical viewpoint].

PubMed

Beier, W

1976-02-15

In the view of theoretical considerations the human course of life is regarded as a generalized motion. It is made an attempt to define terms, such as chronological age, biological age and ageing. In the model of ageing irreversible alterations affecting the organism are described by a complex variable, called vitality, which represents the state of systems. The rate of vitality dV/dt and the biomorphosis of systems are equivalent terms.

Synthesis and biological evaluation of loxoprofen derivatives.

PubMed

Yamakawa, Naoki; Suemasu, Shintaro; Matoyama, Masaaki; Tanaka, Ken-Ichiro; Katsu, Takashi; Miyata, Keishi; Okamoto, Yoshinari; Otsuka, Masami; Mizushima, Tohru

2011-06-01

Non-steroidal anti-inflammatory drugs (NSAIDs) achieve their anti-inflammatory actions through an inhibitory effect on cyclooxygenase (COX). Two COX subtypes, COX-1 and COX-2, are responsible for the majority of COX activity at the gastrointestinal mucosa and in tissues with inflammation, respectively. We previously suggested that both gastric mucosal cell death due to the membrane permeabilization activity of NSAIDs and COX-inhibition at the gastric mucosa are involved in NSAID-induced gastric lesions. We have also reported that loxoprofen has the lowest membrane permeabilization activity among the NSAIDs we tested. In this study, we synthesized a series of loxoprofen derivatives and examined their membrane permeabilization activities and inhibitory effects on COX-1 and COX-2. Among these derivatives, 2-{4'-hydroxy-5-[(2-oxocyclopentyl)methyl]biphenyl-2-yl}propanoate 31 has a specificity for COX-2 over COX-1. Compared to loxoprofen, oral administration of 31 to rats produced fewer gastric lesions but showed an equivalent anti-inflammatory effect. These results suggest that 31 is likely to be a therapeutically beneficial and safer NSAID. Copyright © 2011. Published by Elsevier Ltd.

Design, synthesis, and evaluation of salicyladimine derivatives as multitarget-directed ligands against Alzheimer's disease.

PubMed

Yang, Hua-Li; Cai, Pei; Liu, Qiao-Hong; Yang, Xue-Lian; Fang, Si-Qiang; Tang, Yan-Wei; Wang, Cheng; Wang, Xiao-Bing; Kong, Ling-Yi

2017-11-01

A series of salicyladimine derivatives were designed, synthesized and evaluated as multi-target-directed ligands for the treatment of Alzheimer's disease (AD). Biological activity results demonstrated that some derivatives possessed significant inhibitory activities against amyloid-β (Aβ) aggregation and human monoamine oxidase B (hMAO-B) as well as remarkable antioxidant effects and low cell toxicity. The optimal compound, 5, exhibited excellent potency for inhibition of self-induced Aβ 1-42 aggregation (91.3±2.1%, 25μM), inhibition of hMAO-B (IC 50 , 1.73±0.39μM), antioxidant effects (43.4±2.6μM of IC 50 by DPPH method, 0.67±0.06 trolox equivalent by ABTS method), metal chelation and BBB penetration. Furthermore, compound 5 had neuroprotective effects against ROS generation, H 2 O 2 -induced apoptosis, 6-OHDA-induced cell injury, and a significant in vitro anti-inflammatory activity. Collectively, these findings highlighted that compound 5 was a potential balanced multifunctional neuroprotective agent for the development of anti-AD drugs. Copyright © 2017. Published by Elsevier Ltd.

Lakes as sentinels of climate change

PubMed Central

Adrian, Rita; O’Reilly, Catherine M.; Zagarese, Horacio; Baines, Stephen B.; Hessen, Dag O.; Keller, Wendel; Livingstone, David M.; Sommaruga, Ruben; Straile, Dietmar; Van Donk, Ellen; Weyhenmeyer, Gesa A.; Winder, Monika

2010-01-01

While there is a general sense that lakes can act as sentinels of climate change, their efficacy has not been thoroughly analyzed. We identified the key response variables within a lake that act as indicators of the effects of climate change on both the lake and the catchment. These variables reflect a wide range of physical, chemical, and biological responses to climate. However, the efficacy of the different indicators is affected by regional response to climate change, characteristics of the catchment, and lake mixing regimes. Thus, particular indicators or combinations of indicators are more effective for different lake types and geographic regions. The extraction of climate signals can be further complicated by the influence of other environmental changes, such as eutrophication or acidification, and the equivalent reverse phenomena, in addition to other land-use influences. In many cases, however, confounding factors can be addressed through analytical tools such as detrending or filtering. Lakes are effective sentinels for climate change because they are sensitive to climate, respond rapidly to change, and integrate information about changes in the catchment. PMID:20396409

Tumor necrosis factor-alpha antagonists: differential clinical effects by different biotechnological molecules.

PubMed

Licastro, F; Chiappelli, M; Ianni, M; Porcellini, E

2009-01-01

Inhibitors of tumor necrosis factor-alpha have deeply changed the therapy of several inflammatory human diseases. For instance, clinical management of rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis have profoundly benefited after the introduction of new therapeutic tools, such as antagonist of TNF-alpha molecule. These drugs include etanercept, a soluble TNF-alpha receptor antagonist, three anti-TNF-alpha antibodies, adalimumab, infliximab, golimumab and certolizumab a humanized Fab fragment combined with polyethylene glycol. These compounds efficiently inhibit several TNF-alpha biological-mediated effects, however, they have also shown differential clinical efficacy in several trials from different autoimmune diseases. It is of clinical relevance that non-responders to one of these drugs often positively responded to another. Different mechanisms of action and diversity in pharmacokinetics of these three compounds may partially explain different clinical effects. However, partially diverse pathogenetic mechanisms in different diseases also contribute to differential therapeutic responses. Therefore, these apparently homogeneous agents can not be considered equivalent in their clinically efficacy. Differential therapeutic actions of these drugs may be advantageously used in clinical practice and further improve the great potential of individual TNF-alpha inhibitors.

Studies on the anorectic effect of N-acylphosphatidylethanolamine and phosphatidylethanolamine in mice.

PubMed

Wellner, Niels; Tsuboi, Kazuhito; Madsen, Andreas Nygaard; Holst, Birgitte; Diep, Thi Ai; Nakao, Michiyasu; Tokumura, Akira; Burns, Matthew P; Deutsch, Dale G; Ueda, Natsuo; Hansen, Harald Severin

2011-09-01

N-acyl-phosphatidylethanolamine is a precursor phospholipid for anandamide, oleoylethanolamide, and other N-acylethanolamines, and it may in itself have biological functions in cell membranes. Recently, N-palmitoyl-phosphatidylethanolamine (NAPE) has been reported to function as an anorectic hormone secreted from the gut and acting on the brain (Gillum et al., [5]). In the current study, two of our laboratories independently investigated whether NAPE metabolites may be involved in mediating the anorectic action of NAPE i.p. injected in mice. Thus, the anorectic activity of a non-hydrolysable NAPE analogue, having ether bonds instead of ester bonds at sn1 and sn2 was compared with that of NAPE in molar equivalent doses. Furthermore, the anorectic effect of NAPE in NAPE-hydrolysing phospholipase D knockout animals was investigated. As negative controls, the NAPE precursor phosphatidylethanolamine and the related phospholipids phosphatidylcholine and phosphatidic acid were also tested. All compounds except one were found to inhibit food intake, raising the possibility that the effect of NAPE is non-specific. Copyright © 2011 Elsevier B.V. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Perko, Z; Bortfeld, T; Hong, T

Purpose: The safe use of radiotherapy requires the knowledge of tolerable organ doses. For experimental fractionation schemes (e.g. hypofractionation) these are typically extrapolated from traditional fractionation schedules using the Biologically Effective Dose (BED) model. This work demonstrates that using the mean dose in the standard BED equation may overestimate tolerances, potentially leading to unsafe treatments. Instead, extrapolation of mean dose tolerances should take the spatial dose distribution into account. Methods: A formula has been derived to extrapolate mean physical dose constraints such that they are mean BED equivalent. This formula constitutes a modified BED equation where the influence of themore » spatial dose distribution is summarized in a single parameter, the dose shape factor. To quantify effects we analyzed 14 liver cancer patients previously treated with proton therapy in 5 or 15 fractions, for whom also photon IMRT plans were available. Results: Our work has two main implications. First, in typical clinical plans the dose distribution can have significant effects. When mean dose tolerances are extrapolated from standard fractionation towards hypofractionation they can be overestimated by 10–15%. Second, the shape difference between photon and proton dose distributions can cause 30–40% differences in mean physical dose for plans having the same mean BED. The combined effect when extrapolating proton doses to mean BED equivalent photon doses in traditional 35 fraction regimens resulted in up to 7–8 Gy higher doses than when applying the standard BED formula. This can potentially lead to unsafe treatments (in 1 of the 14 analyzed plans the liver mean dose was above its 32 Gy tolerance). Conclusion: The shape effect should be accounted for to avoid unsafe overestimation of mean dose tolerances, particularly when estimating constraints for hypofractionated regimens. In addition, tolerances established for a given treatment modality cannot necessarily be applied to other modalities with drastically different dose distributions.« less

[Dosimetric aspects in studying the biological action of nonionizing electromagnetic radiation].

PubMed

Karpov, V N; Galkin, A A; Davydov, B I

1984-01-01

In order to clarify mechanisms of biological reactions, it is very important to study the absorption and spatial distribution of the absorbed electromagnetic energy. The procedures and methods of calculating the electromagnetic energy absorption of biological specimens exposed to nonionizing electromagnetic irradiation in a wide frequency range (0-300 GHz) are described. Also presented are formulas and plots to be used in calculating the specific absorption of the dose rate by biological specimens, with the inclusion of resonance absorption, polarization of the incident electromagnetic wave, presence of reflecting surfaces and grounding. The extrapolation of the average energy absorption from one animal species to another and to man is discussed, assuming that spatial and energy distributions are equivalent. The notion of the irradiation quality coefficient is introduced. The magnitudes of the coefficients are given as related to the irradiation frequency and polarization type. A mathematical relation is offered to determine the safety of a complex spectrum of electromagnetic irradiation. The relation takes into consideration different dimensionality of the parameters of the electromagnetic field in the low- and high-frequency ranges.

Thermal injury models for optical treatment of biological tissues: a comparative study.

PubMed

Fanjul-Velez, Felix; Ortega-Quijano, Noe; Salas-Garcia, Irene; Arce-Diego, Jose L

2010-01-01

The interaction of optical radiation with biological tissues causes an increase in the temperature that, depending on its magnitude, can provoke a thermal injury process in the tissue. The establishment of laser irradiation pathological limits constitutes an essential task, as long as it enables to fix and delimit a range of parameters that ensure a safe treatment in laser therapies. These limits can be appropriately described by kinetic models of the damage processes. In this work, we present and compare several models for the study of thermal injury in biological tissues under optical illumination, particularly the Arrhenius thermal damage model and the thermal dosimetry model based on CEM (Cumulative Equivalent Minutes) 43°C. The basic concepts that link the temperature and exposition time with the tissue injury or cellular death are presented, and it will be shown that they enable to establish predictive models for the thermal damage in laser therapies. The results obtained by both models will be compared and discussed, highlighting the main advantages of each one and proposing the most adequate one for optical treatment of biological tissues.

Method for the isolation of biologically active monomeric immunoglobulin A from a plasma fraction.

PubMed

Leibl, H; Tomasits, R; Wolf, H M; Eibl, M M; Mannhalter, J W

1996-04-12

A purification method for immunoglobulin A (IgA) yielding monomeric IgA with a purity of over 97% has been developed. This procedure uses ethanol-precipitated plasma (Cohn fraction III precipitate) as the starting material and includes heparin-Sepharose adsorption, dextran sulfate and ammonium sulfate precipitation, hydroxyapatite chromatography, batch adsorption by an anion-exchange matrix and gel permeation. Additional protein G Sepharose treatment leads to an IgA preparation of greater than 99% purity. The isolated IgA presented with an IgA subclass distribution, equivalent to IgA in unfractionated plasma, and was biologically active, as was shown by its ability to down-modulate Haemophilus influenzae-b-induced IL-6 secretion of human monocytes.

10 CFR 20.1003 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-01-01

... assessment of dose equivalent by the use of devices designed to be worn by an individual; (2) The assessment... equipment) means devices designed to be worn by a single individual for the assessment of dose equivalent... radionuclide in a year by the reference man that would result in a committed effective dose equivalent of 5...

10 CFR 20.1003 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-01-01

... assessment of dose equivalent by the use of devices designed to be worn by an individual; (2) The assessment... equipment) means devices designed to be worn by a single individual for the assessment of dose equivalent... radionuclide in a year by the reference man that would result in a committed effective dose equivalent of 5...

10 CFR 20.1003 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-01-01

... assessment of dose equivalent by the use of devices designed to be worn by an individual; (2) The assessment... equipment) means devices designed to be worn by a single individual for the assessment of dose equivalent... radionuclide in a year by the reference man that would result in a committed effective dose equivalent of 5...

10 CFR 20.1003 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-01-01

... assessment of dose equivalent by the use of devices designed to be worn by an individual; (2) The assessment... equipment) means devices designed to be worn by a single individual for the assessment of dose equivalent... radionuclide in a year by the reference man that would result in a committed effective dose equivalent of 5...

10 CFR 20.1003 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-01-01

... assessment of dose equivalent by the use of devices designed to be worn by an individual; (2) The assessment... equipment) means devices designed to be worn by a single individual for the assessment of dose equivalent... radionuclide in a year by the reference man that would result in a committed effective dose equivalent of 5...

A biologically-inspired multi-joint soft exosuit that can reduce the energy cost of loaded walking.

PubMed

Panizzolo, Fausto A; Galiana, Ignacio; Asbeck, Alan T; Siviy, Christopher; Schmidt, Kai; Holt, Kenneth G; Walsh, Conor J

2016-05-12

Carrying load alters normal walking, imposes additional stress to the musculoskeletal system, and results in an increase in energy consumption and a consequent earlier onset of fatigue. This phenomenon is largely due to increased work requirements in lower extremity joints, in turn requiring higher muscle activation. The aim of this work was to assess the biomechanical and physiological effects of a multi-joint soft exosuit that applies assistive torques to the biological hip and ankle joints during loaded walking. The exosuit was evaluated under three conditions: powered (EXO_ON), unpowered (EXO_OFF) and unpowered removing the equivalent mass of the device (EXO_OFF_EMR). Seven participants walked on an instrumented split-belt treadmill and carried a load equivalent to 30 % their body mass. We assessed their metabolic cost of walking, kinetics, kinematics, and lower limb muscle activation using a portable gas analysis system, motion capture system, and surface electromyography. Our results showed that the exosuit could deliver controlled forces to a wearer. Net metabolic power in the EXO_ON condition (7.5 ± 0.6 W kg(-1)) was 7.3 ± 5.0 % and 14.2 ± 6.1 % lower than in the EXO_OFF_EMR condition (7.9 ± 0.8 W kg(-1); p = 0.027) and in the EXO_OFF condition (8.5 ± 0.9 W kg(-1); p = 0.005), respectively. The exosuit also reduced the total joint positive biological work (sum of hip, knee and ankle) when comparing the EXO_ON condition (1.06 ± 0.16 J kg(-1)) with respect to the EXO_OFF condition (1.28 ± 0.26 J kg(-1); p = 0.020) and to the EXO_OFF_EMR condition (1.22 ± 0.21 J kg(-1); p = 0.007). The results of the present work demonstrate for the first time that a soft wearable robot can improve walking economy. These findings pave the way for future assistive devices that may enhance or restore gait in other applications.

Gender differences and disparities in all-cause and coronary heart disease mortality: epidemiological aspects.

PubMed

Barrett-Connor, Elizabeth

2013-08-01

This overview is primarily concerned with large recent prospective cohort studies of adult populations, not patients, because the latter studies are confounded by differences in medical and surgical management for men vs. women. When early papers are uniquely informative they are also included. Because the focus is on epidemiology, details of age, sex, sample size, and source as well as study methods are provided. Usually the primary outcomes were all-cause or coronary heart disease (CHD) mortality using baseline data from midlife or older adults. Fifty years ago few prospective cohort studies of all-cause or CHD mortality included women. Most epidemiologic studies that included community-dwelling adults did not include both sexes and still do not report men and women separately. Few studies consider both sex (biology) and gender (behavior and environment) differences. Lifespan studies describing survival after live birth are not considered here. The important effects of prenatal and early childhood biologic and behavioral factors on adult mortality are beyond the scope of this review. Clinical trials are not discussed. Overall, presumptive evidence for causality was equivalent for psychosocial and biological exposures, and these attributes were often associated with each other. Inconsistencies or gaps were particularly obvious for studies of sex or gender differences in age and optimal measures of body size for CHD outcomes, and in the striking interface of diabetes and people with the metabolic syndrome, most of whom have unrecognized diabetes. Copyright © 2013 Elsevier Ltd. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gomez, Daniel R., E-mail: dgomez@mdanderson.org; Gillin, Michael; Liao, Zhongxing

Background: Many patients with locally advanced non-small cell lung cancer (NSCLC) cannot undergo concurrent chemotherapy because of comorbidities or poor performance status. Hypofractionated radiation regimens, if tolerable, may provide an option to these patients for effective local control. Methods and Materials: Twenty-five patients were enrolled in a phase 1 dose-escalation trial of proton beam therapy (PBT) from September 2010 through July 2012. Eligible patients had histologically documented lung cancer, thymic tumors, carcinoid tumors, or metastatic thyroid tumors. Concurrent chemotherapy was not allowed, but concurrent treatment with biologic agents was. The dose-escalation schema comprised 15 fractions of 3 Gy(relative biological effectivenessmore » [RBE])/fraction, 3.5 Gy(RBE)/fraction, or 4 Gy(RBE)/fraction. Dose constraints were derived from biologically equivalent doses of standard fractionated treatment. Results: The median follow-up time for patients alive at the time of analysis was 13 months (range, 8-28 months). Fifteen patients received treatment to hilar or mediastinal lymph nodes. Two patients experienced dose-limiting toxicity possibly related to treatment; 1 received 3.5-Gy(RBE) fractions and experienced an in-field tracheoesophageal fistula 9 months after PBT and 1 month after bevacizumab. The other patient received 4-Gy(RBE) fractions and was hospitalized for bacterial pneumonia/radiation pneumonitis 4 months after PBT. Conclusion: Hypofractionated PBT to the thorax delivered over 3 weeks was well tolerated even with significant doses to the lungs and mediastinal structures. Phase 2/3 trials are needed to compare the efficacy of this technique with standard treatment for locally advanced NSCLC.« less

Gender differences and disparities in all-cause and coronary heart disease mortality: epidemiological aspects

PubMed Central

Barrett-Connor, Elizabeth

2013-01-01

This overview is primarily concerned with large recent prospective cohort studies of adult populations, not patients, because the latter studies are confounded by differences in medical and surgical management for men vs. women. When early papers are uniquely informative they are also included. Because the focus is on epidemiology, details of age, sex, sample size, and source as well as study methods are provided. Usually the primary outcomes were all-cause or coronary heart disease (CHD) mortality using baseline data from midlife or older adults. Fifty years ago few prospective cohort studies of all-cause or CHD mortality included women. Most epidemiologic studies that included community-dwelling adults did not include both sexes and still do not report men and women separately. Few studies consider both sex (biology) and gender (behavior and environment) differences. Lifespan studies describing survival after live birth are not considered here. The important effects of prenatal and early childhood biologic and behavioral factors on adult mortality are beyond the scope of this review. Clinical trials are not discussed. Overall, presumptive evidence for causality was equivalent for psychosocial and biological exposures, and these attributes were often associated with each other. Inconsistencies or gaps were particularly obvious for studies of sex or gender differences in age and optimal measures of body size for CHD outcomes, and in the striking interface of diabetes and people with the metabolic syndrome, most of whom have unrecognized diabetes. PMID:24054926

Novel three-dimensional autologous tissue-engineered vaginal tissues using the self-assembly technique.

PubMed

Orabi, Hazem; Saba, Ingrid; Rousseau, Alexandre; Bolduc, Stéphane

2017-02-01

Many diseases necessitate the substitution of vaginal tissues. Current replacement therapies are associated with many complications. In this study, we aimed to create bioengineered neovaginas with the self-assembly technique using autologous vaginal epithelial (VE) and vaginal stromal (VS) cells without the use of exogenous materials and to document the survival and incorporation of these grafts into the tissues of nude female mice. Epithelial and stromal cells were isolated from vaginal biopsies. Stromal cells were driven to form collagen sheets, 3 of which were superimposed to form vaginal stromas. VE cells were seeded on top of these stromas and allowed to mature in an air-liquid interface. The vaginal equivalents were implanted subcutaneously in female nude mice, which were sacrificed after 1 and 2 weeks after surgery. The in vitro and animal-retrieved equivalents were assessed using histologic, functional, and mechanical evaluations. Vaginal equivalents could be handled easily. VE cells formed a well-differentiated epithelial layer with a continuous basement membrane. The equivalent matrix was composed of collagen I and III and elastin. The epithelium, basement membrane, and stroma were comparable to those of native vaginal tissues. The implanted equivalents formed mature vaginal epithelium and matrix that were integrated into the mice tissues. Using the self-assembly technique, in vitro vaginal tissues were created with many functional and biological similarities to native vagina without any foreign material. They formed functional vaginal tissues after in vivo animal implantation. It is appropriate for vaginal substitution and disease modeling for infectious studies, vaginal applicants, and drug testing. Copyright © 2016 Elsevier Inc. All rights reserved.

Effective dose equivalent on the ninth Shuttle--Mir mission (STS-91)

NASA Technical Reports Server (NTRS)

Yasuda, H.; Badhwar, G. D.; Komiyama, T.; Fujitaka, K.

2000-01-01

Organ and tissue doses and effective dose equivalent were measured using a life-size human phantom on the ninth Shuttle-Mir Mission (STS-91, June 1998), a 9.8-day spaceflight at low-Earth orbit (about 400 km in altitude and 51.65 degrees in inclination). The doses were measured at 59 positions using a combination of thermoluminescent dosimeters of Mg(2)SiO(4):Tb (TDMS) and plastic nuclear track detectors (PNTD). In correcting the change in efficiency of the TDMS, it was assumed that reduction of efficiency is attributed predominantly to HZE particles with energy greater than 100 MeV nucleon(-1). A conservative calibration curve was chosen for determining LET from the PNTD track-formation sensitivities. The organ and tissue absorbed doses during the mission ranged from 1.7 to 2.7 mGy and varied by a factor of 1.6. The dose equivalent ranged from 3.4 to 5.2 mSv and varied by a factor of 1.5 on the basis of the dependence of Q on LET in the 1990 recommendations of the ICRP. The effective quality factor (Q(e)) varied from 1.7 to 2.4. The dose equivalents for several radiation-sensitive organs, such as the stomach, lung, gonad and breast, were not significantly different from the skin dose equivalent (H(skin)). The effective dose equivalent was evaluated as 4.1 mSv, which was about 90% of the H(skin).

Reductions in greenhouse gas (GHG) generation and energy consumption in wastewater treatment plants.

PubMed

Yerushalmi, L; Ashrafi, O; Haghighat, F

2013-01-01

Greenhouse gas (GHG) emission and energy consumption by on-site and off-site sources were estimated in two different wastewater treatment plants that used physical-chemical or biological processes for the removal of contaminants, and an anaerobic digester for sludge treatment. Physical-chemical treatment processes were used in the treatment plant of a locomotive repair factory that processed wastewater at 842 kg chemical oxygen demand per day. Approximately 80% of the total GHG emission was related to fossil fuel consumption for energy production. The emission of GHG was reduced by 14.5% with the recovery of biogas that was generated in the anaerobic digester and its further use as an energy source, replacing fossil fuels. The examined biological treatment system used three alternative process designs for the treatment of effluents from pulp and paper mills that processed wastewater at 2,000 kg biochemical oxygen demand per day. The three designs used aerobic, anaerobic, or hybrid aerobic/anaerobic biological processes for the removal of carbonaceous contaminants, and nitrification/denitrification processes for nitrogen removal. Without the recovery and use of biogas, the aerobic, anaerobic, and hybrid treatment systems generated 3,346, 6,554 and 7,056 kg CO(2)-equivalent/day, respectively, while the generated GHG was reduced to 3,152, 6,051, and 6,541 kg CO(2)-equivalent/day with biogas recovery. The recovery and use of biogas was shown to satisfy and exceed the energy needs of the three examined treatment plants. The reduction of operating temperature of the anaerobic digester and anaerobic reactor by 10°C reduced energy demands of the treatment plants by 35.1, 70.6 and 62.9% in the three examined treatment systems, respectively.

Hyaluronate tethered, "smart" multiwalled carbon nanotubes for tumor-targeted delivery of doxorubicin.

PubMed

Datir, Satyajit R; Das, Manasmita; Singh, Raman Preet; Jain, Sanyog

2012-11-21

The present study reports the optimized synthesis, physicochemical characterization, and biological evaluation of a novel, multiwalled carbon nanotube-hyaluronic acid (MWCNT-HA) conjugate, complexed with an anticancer agent, Doxorubicin (DOX) via π-π stacking interaction. The therapeutic conjugate was concomitantly labeled with a near-infrared fluorescent dye, Alexa-Flour-647 (AF-647), and radiotracer Technetium-99m ((99m)Tc) to track its whereabouts both in vitro and in vivo via optical and scintigraphic imaging techniques. Covalent functionalization of MWCNTs with HA facilitated their internalization into human lung adenocarcinoma, A549 cells via hyaluronan receptors (HR) mediated endocytosis. Internalized nanotubes showed lysosomal trafficking, followed by low pH-triggered DOX release under endolysosomal conditions. Consequently, DOX-loaded HA-MWCNTs exhibited 3.2 times higher cytotoxicity and increased apoptotic activity than free DOX in equivalent concentrations. Organ distribution studies in Ehlrich ascites tumor (EAT) bearing mice model indicated that tumor specific localization of (99m)Tc-MWCNT-HA-DOX is significantly higher than both free drug and nontargeted MWCNTs. Pharmacodynamic studies in chemically breast-cancer-induced rats showed that the tumor-growth inhibitory effect of HA-MWCNT-DOX was 5 times higher than free DOX in equivalent concentration. DOX delivered through HA-MWCNTs was devoid of any detectable cardiotoxity, hepatotoxicity, or nephrotoxicity. All these promising attributes make HA-MWCNTs a "smart" platform for tumor-targeted delivery of anticancer agents.

Variability in tannin content, chemistry and activity in a diverse group of tannin containing sorghum cultivars.

PubMed

Kaufman, Rhett C; Herald, Thomas J; Bean, Scott R; Wilson, Jeff D; Tuinstra, Mitch R

2013-03-30

Tannins are large polyphenolic polymers and are known to bind proteins, limiting their digestibility, but are also excellent antioxidants. Numerous studies investigating the functional properties of sorghum tannin have been conducted by comparing grain samples from different sorghum lines without considering the other intrinsic characteristics of the grain. The purpose of this study was to remove the confounding intrinsic factors present in the endosperm so the effect of the tannins could be evaluated utilizing a unique decortication/reconstitution procedure. The tannin content of the 14 cultivars tested ranged from 2.3 to 67.2 catechin equivalents. The bran fractions were studied for their impact on protein binding and antioxidant capacity. Protein digestibility by pepsin ranged from 8% to 58% at the highest tannin level addition. Protein binding ranged from 3.11 to 16.33 g blue bovine serum albumin kg⁻¹ bran. Antioxidant capacity ranged from 81.33 to 1122.54 µmol Trolox equivalents g⁻¹ bran. High-performance size-exclusion chromatography detailed molecular size distributions of the tannin polymers and relationship to tannin functionality. The tannin content and composition play a significant role in determining tannin functionality. These differences will allow for selections of high-tannin sorghums with consideration of the biological activities of the tannins. Published 2012. This article is a U.S. Government work and is in the public domain in the USA.

Antioxidant activity of hydroalcholic extract of Ferula gummosa Boiss roots.

PubMed

Ebrahimzadeh, M A; Nabavi, S M; Nabavi, S F; Dehpour, A A

2011-06-01

Ferula gummosa Boiss is native to central Asia. This plant has traditionally been used in the treatment of many diseases. The antihypoxic and antioxidant activities of Ferula gummosa roots were investigated. 1,1-diphenyl-2-picryl hydrazyl radical (DPPH), nitric oxide and hydrogen peroxide scavenging activities, Fe2+ chelating ability, reducing power and hemoglobin-induced linoleic acid peroxidation were used to evaluate antioxidant activities. Antihemolytic activity was evaluated by H2O2 induced hemolysis in rat erythrocytes. The total amount of phenolic compounds was determined as gallic acid equivalents and total flavonoid contents were calculated as quercetin equivalents from a calibration curve. The extracts showed moderate antioxidant activity in some models. IC50 for DPPH radical-scavenging activity was 579.6 +/- 19.4 microg/ml. The extracts showed weak nitric oxide-scavenging activity between 0.1 and 1.6 mg ml(-1) but showed good Fe2+ chelating ability. IC50 was 895.5 +/- 24.1 microg/ml. The extract also exhibited low antioxidant activity in the linoleic acid model but were capable of scavenging hydrogen peroxide in a concentration dependent manner. Tested extract show moderate activity in H2O2 induced hemolysis in rat erythrocytes which was not comparable with vitamin C. F. gummosa Boiss root showed different level antioxidant and antihemolytic activities. Biological effects may be attributed, at least in part, to the presence of phenols and flavonoids in the extract.

Experimental demonstration of a multi-wavelength distributed feedback semiconductor laser array with an equivalent chirped grating profile based on the equivalent chirp technology.

PubMed

Li, Wangzhe; Zhang, Xia; Yao, Jianping

2013-08-26

We report, to the best of our knowledge, the first realization of a multi-wavelength distributed feedback (DFB) semiconductor laser array with an equivalent chirped grating profile based on equivalent chirp technology. All the lasers in the laser array have an identical grating period with an equivalent chirped grating structure, which are realized by nonuniform sampling of the gratings. Different wavelengths are achieved by changing the sampling functions. A multi-wavelength DFB semiconductor laser array is fabricated and the lasing performance is evaluated. The results show that the equivalent chirp technology is an effective solution for monolithic integration of a multi-wavelength laser array with potential for large volume fabrication.

Neutron Exposures in Human Cells: Bystander Effect and Relative Biological Effectiveness

PubMed Central

Seth, Isheeta; Schwartz, Jeffrey L.; Stewart, Robert D.; Emery, Robert; Joiner, Michael C.; Tucker, James D.

2014-01-01

Bystander effects have been observed repeatedly in mammalian cells following photon and alpha particle irradiation. However, few studies have been performed to investigate bystander effects arising from neutron irradiation. Here we asked whether neutrons also induce a bystander effect in two normal human lymphoblastoid cell lines. These cells were exposed to fast neutrons produced by targeting a near-monoenergetic 50.5 MeV proton beam at a Be target (17 MeV average neutron energy), and irradiated-cell conditioned media (ICCM) was transferred to unirradiated cells. The cytokinesis-block micronucleus assay was used to quantify genetic damage in radiation-naïve cells exposed to ICCM from cultures that received 0 (control), 0.5, 1, 1.5, 2, 3 or 4 Gy neutrons. Cells grown in ICCM from irradiated cells showed no significant increase in the frequencies of micronuclei or nucleoplasmic bridges compared to cells grown in ICCM from sham irradiated cells for either cell line. However, the neutron beam has a photon dose-contamination of 5%, which may modulate a neutron-induced bystander effect. To determine whether these low doses of contaminating photons can induce a bystander effect, cells were irradiated with cobalt-60 at doses equivalent to the percent contamination for each neutron dose. No significant increase in the frequencies of micronuclei or bridges was observed at these doses of photons for either cell line when cultured in ICCM. As expected, high doses of photons induced a clear bystander effect in both cell lines for micronuclei and bridges (p<0.0001). These data indicate that neutrons do not induce a bystander effect in these cells. Finally, neutrons had a relative biological effectiveness of 2.0±0.13 for micronuclei and 5.8±2.9 for bridges compared to cobalt-60. These results may be relevant to radiation therapy with fast neutrons and for regulatory agencies setting standards for neutron radiation protection and safety. PMID:24896095

Neutron exposures in human cells: bystander effect and relative biological effectiveness.

PubMed

Seth, Isheeta; Schwartz, Jeffrey L; Stewart, Robert D; Emery, Robert; Joiner, Michael C; Tucker, James D

2014-01-01

Bystander effects have been observed repeatedly in mammalian cells following photon and alpha particle irradiation. However, few studies have been performed to investigate bystander effects arising from neutron irradiation. Here we asked whether neutrons also induce a bystander effect in two normal human lymphoblastoid cell lines. These cells were exposed to fast neutrons produced by targeting a near-monoenergetic 50.5 MeV proton beam at a Be target (17 MeV average neutron energy), and irradiated-cell conditioned media (ICCM) was transferred to unirradiated cells. The cytokinesis-block micronucleus assay was used to quantify genetic damage in radiation-naïve cells exposed to ICCM from cultures that received 0 (control), 0.5, 1, 1.5, 2, 3 or 4 Gy neutrons. Cells grown in ICCM from irradiated cells showed no significant increase in the frequencies of micronuclei or nucleoplasmic bridges compared to cells grown in ICCM from sham irradiated cells for either cell line. However, the neutron beam has a photon dose-contamination of 5%, which may modulate a neutron-induced bystander effect. To determine whether these low doses of contaminating photons can induce a bystander effect, cells were irradiated with cobalt-60 at doses equivalent to the percent contamination for each neutron dose. No significant increase in the frequencies of micronuclei or bridges was observed at these doses of photons for either cell line when cultured in ICCM. As expected, high doses of photons induced a clear bystander effect in both cell lines for micronuclei and bridges (p<0.0001). These data indicate that neutrons do not induce a bystander effect in these cells. Finally, neutrons had a relative biological effectiveness of 2.0 ± 0.13 for micronuclei and 5.8 ± 2.9 for bridges compared to cobalt-60. These results may be relevant to radiation therapy with fast neutrons and for regulatory agencies setting standards for neutron radiation protection and safety.

Defining Equivalence in Medical Education Evaluation and Research: Does a Distribution-Based Approach Work?

ERIC Educational Resources Information Center

Rusticus, Shayna A.; Eva, Kevin W.

2016-01-01

Educators often seek to demonstrate the equivalence of groups, such as whether or not students achieve comparable success regardless of the site at which they trained. A methodological consideration that is often underappreciated is how to operationalize equivalence. This study examined whether a distribution-based approach, based on effect size,…

WWC Review of the Report "Benefits of Practicing 4 = 2 + 2: Nontraditional Problem Formats Facilitate Children's Understanding of Mathematical Equivalence." What Works Clearinghouse Single Study Review

ERIC Educational Resources Information Center

What Works Clearinghouse, 2014

2014-01-01

The 2011 study, "Benefits of Practicing 4 = 2 + 2: Nontraditional Problem Formats Facilitate Children's Understanding of Mathematical Equivalence," examined the effects of addition practice using nontraditional problem formats on students' understanding of mathematical equivalence. In nontraditional problem formats, operations appear on…

Comparison of a Stimulus Equivalence Protocol and Traditional Lecture for Teaching Single-Subject Designs

ERIC Educational Resources Information Center

Lovett, Sadie; Rehfeldt, Ruth Anne; Garcia, Yors; Dunning, Johnna

2011-01-01

This study compared the effects of a computer-based stimulus equivalence protocol to a traditional lecture format in teaching single-subject experimental design concepts to undergraduate students. Participants were assigned to either an equivalence or a lecture group, and performance on a paper-and-pencil test that targeted relations among the…

75 FR 71777 - Self-Regulatory Organizations; NYSE Amex LLC; Notice of Filing and Immediate Effectiveness of...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-24

... exemption rules among exchanges. The ``options contract equivalent of the net delta'' of a hedged equity...\\ The term ``options contract equivalent of the net delta'' is defined in Rule 904, Commentary .10(c) as... delta and options contract equivalent of the net delta will be calculated for each respective option...

Equivalent model and power flow model for electric railway traction network

NASA Astrophysics Data System (ADS)

Wang, Feng

2018-05-01

An equivalent model of the Cable Traction Network (CTN) considering the distributed capacitance effect of the cable system is proposed. The model can be divided into 110kV side and 27.5kV side two kinds. The 110kV side equivalent model can be used to calculate the power supply capacity of the CTN. The 27.5kV side equivalent model can be used to solve the voltage of the catenary. Based on the equivalent simplified model of CTN, the power flow model of CTN which involves the reactive power compensation coefficient and the interaction of voltage and current, is derived.

Phytochemical Composition and Biological Activities of Selected Wild Berries (Rubus moluccanus L., R. fraxinifolius Poir., and R. alpestris Blume)

PubMed Central

Abu Bakar, Mohd Fadzelly; Ismail, Nur Amalina; Isha, Azizul; Mei Ling, Angelina Lee

2016-01-01

Berries, from the genus Rubus, are among the vital components in a healthy diet. In this study, 80% methanol extracts from the three wild Rubus species (Rubus moluccanus L., Rubus fraxinifolius Poir., and Rubus alpestris Blume) were evaluated for their phytochemical contents (total phenolics, flavonoid, anthocyanin, and carotenoid content), antioxidant (DPPH, FRAP, and ABTS assays), antiacetylcholinesterase, and antibacterial activities. GC-MS was used for quantification of naturally occurring phytochemicals. The results showed that R. alpestris contained the highest total phenolic [24.25 ± 0.1 mg gallic acid equivalent (GAE)/g] and carotenoid content [21.86 ± 0.63 mg β-carotene equivalents (BC)/g], as well as the highest DPPH scavenging and FRAP activities. The highest total flavonoid [18.17 ± 0.20 mg catechin equivalents (CE)/g] and anthocyanin content [36.96 ± 0.39 mg cyanidin-3-glucoside equivalents (c-3-gE)/g] have been shown by R. moluccanus. For antibacterial assays, R. moluccanus and R. alpestris extracts showed mild inhibition towards Bacillus subtilis, Staphylococcus aureus, Escherichia coli, and Salmonella enteritidis. Anticholinesterase activity for all extracts was in the range of 23–26%. The GC-MS analysis revealed the presence of at least 12, 21, and 7 different organic compounds in 80% methanol extracts of R. alpestris, R. moluccanus, and R. fraxinifolius, respectively, which might contribute to the bioactivity. PMID:27437023

Head-to-head randomized trials are mostly industry sponsored and almost always favor the industry sponsor.

PubMed

Flacco, Maria Elena; Manzoli, Lamberto; Boccia, Stefania; Capasso, Lorenzo; Aleksovska, Katina; Rosso, Annalisa; Scaioli, Giacomo; De Vito, Corrado; Siliquini, Roberta; Villari, Paolo; Ioannidis, John P A

2015-07-01

To map the current status of head-to-head comparative randomized evidence and to assess whether funding may impact on trial design and results. From a 50% random sample of the randomized controlled trials (RCTs) published in journals indexed in PubMed during 2011, we selected the trials with ≥ 100 participants, evaluating the efficacy and safety of drugs, biologics, and medical devices through a head-to-head comparison. We analyzed 319 trials. Overall, 238,386 of the 289,718 randomized subjects (82.3%) were included in the 182 trials funded by companies. Of the 182 industry-sponsored trials, only 23 had two industry sponsors and only three involved truly antagonistic comparisons. Industry-sponsored trials were larger, more commonly registered, used more frequently noninferiority/equivalence designs, had higher citation impact, and were more likely to have "favorable" results (superiority or noninferiority/equivalence for the experimental treatment) than nonindustry-sponsored trials. Industry funding [odds ratio (OR) 2.8; 95% confidence interval (CI): 1.6, 4.7] and noninferiority/equivalence designs (OR 3.2; 95% CI: 1.5, 6.6), but not sample size, were strongly associated with "favorable" findings. Fifty-five of the 57 (96.5%) industry-funded noninferiority/equivalence trials got desirable "favorable" results. The literature of head-to-head RCTs is dominated by the industry. Industry-sponsored comparative assessments systematically yield favorable results for the sponsors, even more so when noninferiority designs are involved. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Influence of Selected Organic Micropollutants on Organisms

NASA Astrophysics Data System (ADS)

Włodarczyk-Makuła, Maria

2017-03-01

This article describes the toxicity of organic micropollutants on tested microorganisms. Itis a current issue because organic micropollutants are identified in all elements of environmental (surface water, ground water, soils) and in food products. The organic micropollutants include: polychlorinated dibenzodioxyns PCDD, polychlorinated dibenzofurans PCDF, polychlorinated biphenyls PCB, polycyclic aromatic hydrocarbons PAH, halogenated compounds and by-products of water treatment. Some organic compounds cause hazard for health and human life due to their estrogenic biological activity, carcinogenic, mutagenic or teratogenic activity. The influence on organisms indicators of these compounds based on literature data were presented. The level of TEQ (toxic equivalency) in response to organic chlorine derivatives (PCDDs, PCDF, PCBs) is usually determined by toxic equivalency factor (TEF). The International Agency for Research on Cancer classifies organic micropollutants as carcinogenic to humans (Group 1), possibly carcinogenic (Group 2A) or probably carcinogenic to humans (Group 2B).

Mathematics reflecting sensorimotor organization.

PubMed

McCollum, Gin

2003-02-01

This review combines short presentations of several mathematical approaches that conceptualize issues in sensorimotor neuroscience from different perspectives and levels of analysis. The intricate organization of neural structures and sensorimotor performance calls for characterization using a variety of mathematical approaches. This review points out the prospects for mathematical neuroscience: in addition to computational approaches, there is a wide variety of mathematical approaches that provide insight into the organization of neural systems. By starting from the perspective that provides the greatest clarity, a mathematical approach avoids specificity that is inaccurate in characterizing the inherent biological organization. Approaches presented include the mathematics of ordered structures, motion-phase space, subject-coincident coordinates, equivalence classes, topological biodynamics, rhythm space metric, and conditional dynamics. Issues considered in this paper include unification of levels of analysis, response equivalence, convergence, relationship of physics to motor control, support of rhythms, state transitions, and focussing on low-dimensional subspaces of a high-dimensional sensorimotor space.

Spatial variability of isoproturon mineralizing activity within an agricultural field: geostatistical analysis of simple physicochemical and microbiological soil parameters.

PubMed

El Sebai, T; Lagacherie, B; Soulas, G; Martin-Laurent, F

2007-02-01

We assessed the spatial variability of isoproturon mineralization in relation to that of physicochemical and biological parameters in fifty soil samples regularly collected along a sampling grid delimited across a 0.36 ha field plot (40 x 90 m). Only faint relationships were observed between isoproturon mineralization and the soil pH, microbial C biomass, and organic nitrogen. Considerable spatial variability was observed for six of the nine parameters tested (isoproturon mineralization rates, organic nitrogen, genetic structure of the microbial communities, soil pH, microbial biomass and equivalent humidity). The map of isoproturon mineralization rates distribution was similar to that of soil pH, microbial biomass, and organic nitrogen but different from those of structure of the microbial communities and equivalent humidity. Geostatistics revealed that the spatial heterogeneity in the rate of degradation of isoproturon corresponded to that of soil pH and microbial biomass.

Effects of equivalent series resistance on the noise mitigation performance of piezoelectric shunt damping

NASA Astrophysics Data System (ADS)

Lai, Szu Cheng; Sharifzadeh Mirshekarloo, Meysam; Yao, Kui

2017-05-01

Piezoelectric shunt damping (PSD) utilizes an electrically-shunted piezoelectric damper attached on a panel structure to suppress the transmission of acoustic noise. The paper develops an understanding on the effects of equivalent series resistance (ESR) of the piezoelectric damper in a PSD system on noise mitigation performance, and demonstrates that an increased ESR leads to a significant rise in the noise transmissibility due to reduction in the system’s mechanical damping. It is further demonstrated with experimental results that ESR effects can be compensated in the shunt circuit to significantly improve the noise mitigation performance. A theoretical electrical equivalent model of the PSD incorporating the ESR is established for quantitative analysis of ESR effects on noise mitigation.

Does biological intimacy shape ecological network structure? A test using a brood pollination mutualism on continental and oceanic islands.

PubMed

Hembry, David H; Raimundo, Rafael L G; Newman, Erica A; Atkinson, Lesje; Guo, Chang; Guimarães, Paulo R; Gillespie, Rosemary G

2018-04-25

Biological intimacy-the degree of physical proximity or integration of partner taxa during their life cycles-is thought to promote the evolution of reciprocal specialization and modularity in the networks formed by co-occurring mutualistic species, but this hypothesis has rarely been tested. Here, we test this "biological intimacy hypothesis" by comparing the network architecture of brood pollination mutualisms, in which specialized insects are simultaneously parasites (as larvae) and pollinators (as adults) of their host plants to that of other mutualisms which vary in their biological intimacy (including ant-myrmecophyte, ant-extrafloral nectary, plant-pollinator and plant-seed disperser assemblages). We use a novel dataset sampled from leafflower trees (Phyllanthaceae: Phyllanthus s. l. [Glochidion]) and their pollinating leafflower moths (Lepidoptera: Epicephala) on three oceanic islands (French Polynesia) and compare it to equivalent published data from congeners on continental islands (Japan). We infer taxonomic diversity of leafflower moths using multilocus molecular phylogenetic analysis and examine several network structural properties: modularity (compartmentalization), reciprocality (symmetry) of specialization and algebraic connectivity. We find that most leafflower-moth networks are reciprocally specialized and modular, as hypothesized. However, we also find that two oceanic island networks differ in their modularity and reciprocal specialization from the others, as a result of a supergeneralist moth taxon which interacts with nine of 10 available hosts. Our results generally support the biological intimacy hypothesis, finding that leafflower-moth networks (usually) share a reciprocally specialized and modular structure with other intimate mutualisms such as ant-myrmecophyte symbioses, but unlike nonintimate mutualisms such as seed dispersal and nonintimate pollination. Additionally, we show that generalists-common in nonintimate mutualisms-can also evolve in intimate mutualisms, and that their effect is similar in both types of assemblages: once generalists emerge they reshape the network organization by connecting otherwise isolated modules. © 2018 The Authors. Journal of Animal Ecology © 2018 British Ecological Society.

Process for magnetic beneficiating petroleum cracking catalyst

DOEpatents

Doctor, R.D.

1993-10-05

A process is described for beneficiating a particulate zeolite petroleum cracking catalyst having metal values in excess of 1000 ppm nickel equivalents. The particulate catalyst is passed through a magnetic field in the range of from about 2 Tesla to about 5 Tesla generated by a superconducting quadrupole open-gradient magnetic system for a time sufficient to effect separation of said catalyst into a plurality of zones having different nickel equivalent concentrations. A first zone has nickel equivalents of about 6,000 ppm and greater, a second zone has nickel equivalents in the range of from about 2000 ppm to about 6000 ppm, and a third zone has nickel equivalents of about 2000 ppm and less. The zones of catalyst are separated and the second zone material is recycled to a fluidized bed of zeolite petroleum cracking catalyst. The low nickel equivalent zone is treated while the high nickel equivalent zone is discarded. 1 figures.

Process for magnetic beneficiating petroleum cracking catalyst

DOEpatents

Doctor, Richard D.

1993-01-01

A process for beneficiating a particulate zeolite petroleum cracking catalyst having metal values in excess of 1000 ppm nickel equivalents. The particulate catalyst is passed through a magnetic field in the range of from about 2 Tesla to about 5 Tesla generated by a superconducting quadrupole open-gradient magnetic system for a time sufficient to effect separation of said catalyst into a plurality of zones having different nickel equivalent concentrations. A first zone has nickel equivalents of about 6,000 ppm and greater, a second zone has nickel equivalents in the range of from about 2000 ppm to about 6000 ppm, and a third zone has nickel equivalents of about 2000 ppm and less. The zones of catalyst are separated and the second zone material is recycled to a fluidized bed of zeolite petroleum cracking catalyst. The low nickel equivalent zone is treated while the high nickel equivalent zone is discarded.

Antimelanogenic Efficacy of Melasolv (3,4,5-Trimethoxycinnamate Thymol Ester) in Melanocytes and Three-Dimensional Human Skin Equivalent.

PubMed

Lee, John Hwan; Lee, Eun-Soo; Bae, Il-Hong; Hwang, Jeong-Ah; Kim, Se-Hwa; Kim, Dae-Yong; Park, Nok-Hyun; Rho, Ho Sik; Kim, Yong Jin; Oh, Seong-Geun; Lee, Chang Seok

2017-01-01

Excessive melanogenesis often causes unaesthetic hyperpigmentation. In a previous report, our group introduced a newly synthesized depigmentary agent, Melasolv™ (3,4,5-trimethoxycinnamate thymol ester). In this study, we demonstrated the significant whitening efficacy of Melasolv using various melanocytes and human skin equivalents as in vitro experimental systems. The depigmentary effect of Melasolv was tested in melan-a cells (immortalized normal murine melanocytes), α-melanocyte-stimulating hormone (α-MSH)-stimulated B16 murine melanoma cells, primary normal human melanocytes (NHMs), and human skin equivalent (MelanoDerm). The whitening efficacy of Melasolv was further demonstrated by photography, time-lapse microscopy, Fontana-Masson (F&M) staining, and 2-photon microscopy. Melasolv significantly inhibited melanogenesis in the melan-a and α-MSH-stimulated B16 cells. In human systems, Melasolv also clearly showed a whitening effect in NHMs and human skin equivalent, reflecting a decrease in melanin content. F&M staining and 2-photon microscopy revealed that Melasolv suppressed melanin transfer into multiple epidermal layers from melanocytes as well as melanin synthesis in human skin equivalent. Our study showed that Melasolv clearly exerts a whitening effect on various melanocytes and human skin equivalent. These results suggest the possibility that Melasolv can be used as a depigmentary agent to treat pigmentary disorders as well as an active ingredient in cosmetics to increase whitening efficacy. © 2017 S. Karger AG, Basel.

Revised Modelling of the Addition of Synchronous Chemotherapy to Radiotherapy in Squamous Cell Carcinoma of the Head and Neck-A Low α/β?

PubMed

Best, James; Fong, Charles; Benghiat, Helen; Mehanna, Hisham; Glaholm, John; Hartley, Andrew

2018-06-13

Background: The effect of synchronous chemotherapy in squamous cell carcinoma of the head and neck (SCCHN) has been modelled as additional Biologically Effective Dose (BED) or as a prolonged tumour cell turnover time during accelerated repopulation. Such models may not accurately predict the local control seen when hypofractionated accelerated radiotherapy is used with synchronous chemotherapy. Methods: For the purposes of this study three isoeffect relationships were assumed: Firstly, from the RTOG 0129 trial, synchronous cisplatin chemotherapy with 70 Gy in 35 fractions over 46 days results in equivalent local control to synchronous cisplatin chemotherapy with 36 Gy in 18# followed by 36 Gy in 24# (2# per day) over a total of 39 days. Secondly, in line with primary local control outcomes from the PET-Neck study, synchronous cisplatin chemotherapy with 70 Gy in 35# over 46 days results in equivalent local control to synchronous cisplatin chemotherapy delivered with 65 Gy in 30# over 39 days. Thirdly, from meta-analysis data, 70 Gy in 35# over 46 days with synchronous cisplatin results in equivalent local control to 84 Gy in 70# over 46 days delivered without synchronous chemotherapy. Using the linear quadratic equation the above isoeffect relationships were expressed algebraically to determine values of α , α/β , and k for SCCHN when treated with synchronous cisplatin using standard parameters for the radiotherapy alone schedule ( α = 0.3 Gy −1 , α/β = 10 Gy, and k = 0.42 Gy 10 day −1 ). Results: The values derived for α/β , α and k were 2 Gy, 0.20 and 0.21 Gy −1 , and 0.65 and 0.71 Gy₂day −1 . Conclusions: Within the limitations of the assumptions made, this model suggests that accelerated repopulation may remain a significant factor when synchronous chemotherapy is delivered with radiotherapy in SCCHN. The finding of a low α/β for SCCHN treated with cisplatin suggests a greater tumour susceptibility to increasing dose per fraction and underlines the importance of the completion of randomized trials examining the role of hypofractionated acceleration in SCCHN.

What Do Contrast Threshold Equivalent Noise Studies Actually Measure? Noise vs. Nonlinearity in Different Masking Paradigms

PubMed Central

Baldwin, Alex S.; Baker, Daniel H.; Hess, Robert F.

2016-01-01

The internal noise present in a linear system can be quantified by the equivalent noise method. By measuring the effect that applying external noise to the system’s input has on its output one can estimate the variance of this internal noise. By applying this simple “linear amplifier” model to the human visual system, one can entirely explain an observer’s detection performance by a combination of the internal noise variance and their efficiency relative to an ideal observer. Studies using this method rely on two crucial factors: firstly that the external noise in their stimuli behaves like the visual system’s internal noise in the dimension of interest, and secondly that the assumptions underlying their model are correct (e.g. linearity). Here we explore the effects of these two factors while applying the equivalent noise method to investigate the contrast sensitivity function (CSF). We compare the results at 0.5 and 6 c/deg from the equivalent noise method against those we would expect based on pedestal masking data collected from the same observers. We find that the loss of sensitivity with increasing spatial frequency results from changes in the saturation constant of the gain control nonlinearity, and that this only masquerades as a change in internal noise under the equivalent noise method. Part of the effect we find can be attributed to the optical transfer function of the eye. The remainder can be explained by either changes in effective input gain, divisive suppression, or a combination of the two. Given these effects the efficiency of our observers approaches the ideal level. We show the importance of considering these factors in equivalent noise studies. PMID:26953796

What Do Contrast Threshold Equivalent Noise Studies Actually Measure? Noise vs. Nonlinearity in Different Masking Paradigms.

PubMed

Baldwin, Alex S; Baker, Daniel H; Hess, Robert F

2016-01-01

The internal noise present in a linear system can be quantified by the equivalent noise method. By measuring the effect that applying external noise to the system's input has on its output one can estimate the variance of this internal noise. By applying this simple "linear amplifier" model to the human visual system, one can entirely explain an observer's detection performance by a combination of the internal noise variance and their efficiency relative to an ideal observer. Studies using this method rely on two crucial factors: firstly that the external noise in their stimuli behaves like the visual system's internal noise in the dimension of interest, and secondly that the assumptions underlying their model are correct (e.g. linearity). Here we explore the effects of these two factors while applying the equivalent noise method to investigate the contrast sensitivity function (CSF). We compare the results at 0.5 and 6 c/deg from the equivalent noise method against those we would expect based on pedestal masking data collected from the same observers. We find that the loss of sensitivity with increasing spatial frequency results from changes in the saturation constant of the gain control nonlinearity, and that this only masquerades as a change in internal noise under the equivalent noise method. Part of the effect we find can be attributed to the optical transfer function of the eye. The remainder can be explained by either changes in effective input gain, divisive suppression, or a combination of the two. Given these effects the efficiency of our observers approaches the ideal level. We show the importance of considering these factors in equivalent noise studies.

Glucose lowering effect of transgenic human insulin-like growth factor-I from rice: in vitro and in vivo studies

PubMed Central

2011-01-01

Background Human insulin-like growth factor-I (hIGF-I) is a growth factor which is highly resemble to insulin. It is essential for cell proliferation and has been proposed for treatment of various endocrine-associated diseases including growth hormone insensitivity syndrome and diabetes mellitus. In the present study, an efficient plant expression system was developed to produce biologically active recombinant hIGF-I (rhIGF-I) in transgenic rice grains. Results The plant-codon-optimized hIGF-I was introduced into rice via Agrobacterium-mediated transformation. To enhance the stability and yield of rhIGF-I, the endoplasmic reticulum-retention signal and glutelin signal peptide were used to deliver rhIGF-I to endoplasmic reticulum for stable accumulation. We found that only glutelin signal peptide could lead to successful expression of hIGF-I and one gram of hIGF-I rice grain possessed the maximum activity level equivalent to 3.2 micro molar of commercial rhIGF-I. In vitro functional analysis showed that the rice-derived rhIGF-I was effective in inducing membrane ruffling and glucose uptake on rat skeletal muscle cells. Oral meal test with rice-containing rhIGF-I acutely reduced blood glucose levels in streptozotocin-induced and Zucker diabetic rats, whereas it had no effect in normal rats. Conclusion Our findings provided an alternative expression system to produce large quantities of biologically active rhIGF-I. The provision of large quantity of recombinant proteins will promote further research on the therapeutic potential of rhIGF-I. PMID:21486461

Evaluation of biologically mediated changes in oil sands naphthenic acid composition by Chlamydomonas reinhardtii using negative-ion electrospray orbitrap mass spectrometry.

PubMed

Goff, Kira L; Peru, Kerry; Wilson, Kenneth E; Headley, John V

2014-08-01

Industrial activity associated with oil-sands extraction in Canada's Athabasca region produces a variety of contaminants of concern, including naphthenic acid fraction components (NAFCs). NAFCs are a complex mixture of organic compounds that are poorly understood both in terms of their chemical composition and effects on the environment. NAFC toxicity in the unicellular green algae Chlamydomonas reinhardtii P.A.Dangeard was correlated with the presence of the algal cell wall. It was suggested that the toxicity of NAFCs in C. reinhardtii was due to surfactant effects. Surfactant-cell wall interactions are specific and governed by the compound class and structure, and by the nature of the biological material. Here, we investigate the effects of wildtype (WT) C. reinhardtii and two cell-wall mutants on specific classes of NAFCs when growing cultures were treated with a 100 mg · L(-1) solution of NAFCs. Changes in the NAFC composition in the media were examined using high resolution mass spectrometry over a period of 4 d. Algal mediated changes in the NAFCs were limited to specific classes of NAFCs. In particular, the removal of large, classical naphthenic acids, with a double bond equivalent of 8, was observed in WT C. reinhardtii cultures. The observed algal mediated changes in NAFC composition would have been masked by low resolution mass spectrometry and highlight the importance of this tool in examining bioremediation of complex mixtures of NAFCs. © 2014 Phycological Society of America.

Daily Rhythms of Hunger and Satiety in Healthy Men during One Week of Sleep Restriction and Circadian Misalignment.

PubMed

Sargent, Charli; Zhou, Xuan; Matthews, Raymond W; Darwent, David; Roach, Gregory D

2016-01-29

The impact of sleep restriction on the endogenous circadian rhythms of hunger and satiety were examined in 28 healthy young men. Participants were scheduled to 2 × 24-h days of baseline followed by 8 × 28-h days of forced desynchrony during which sleep was either moderately restricted (equivalent to 6 h in bed/24 h; n = 14) or severely restricted (equivalent to 4 h in bed/24 h; n = 14). Self-reported hunger and satisfaction were assessed every 2.5 h during wake periods using visual analogue scales. Participants were served standardised meals and snacks at regular intervals and were not permitted to eat ad libitum. Core body temperature was continuously recorded with rectal thermistors to determine circadian phase. Both hunger and satiety exhibited a marked endogenous circadian rhythm. Hunger was highest, and satiety was lowest, in the biological evening (i.e., ~17:00-21:00 h) whereas hunger was lowest, and satiety was highest in the biological night (i.e., 01:00-05:00 h). The results are consistent with expectations based on previous reports and may explain in some part the decrease in appetite that is commonly reported by individuals who are required to work at night. Interestingly, the endogenous rhythms of hunger and satiety do not appear to be altered by severe--as compared to moderate--sleep restriction.

Relevance and limits of the principle of "equivalence of care" in prison medicine.

PubMed

Niveau, Gérard

2007-10-01

The principle of "equivalence of care" in prison medicine is a principle by which prison health services are obliged to provide prisoners with care of a quality equivalent to that provided for the general public in the same country. It is cited in numerous national and international directives and recommendations. The principle of equivalence is extremely relevant from the point of view of normative ethics but requires adaptation from the point of view of applied ethics. From a clinical point of view, the principle of equivalence is often insufficient to take account of the adaptations necessary for the organization of care in a correctional setting. The principle of equivalence is cost-effective in general, but has to be overstepped to ensure the humane management of certain special cases.

Protracted exposure to fallout: the Rongelap and Utirik experience.

PubMed

Lessard, E T; Miltenberger, R P; Cohn, S H; Musolino, S V; Conard, R A

1984-03-01

From June 1946 to August 1958, the U.S. Department of Defense and the U.S. Atomic Energy Commission (AEC) conducted nuclear weapons tests in the Northern Marshall Islands. On 1 March 1954, BRAVO, an above-ground test in the Castle series, produced high levels of radioactive material, some of which subsequently fell on Rongelap and Utirik Atolls due to an unexpected wind shift. On 3 March 1954, the inhabitants of these atolls were moved out of the affected area. They later returned to Utirik in June 1954 and to Rongelap in June 1957. Comprehensive environmental and personnel radiological monitoring programs were initiated in the mid 1950s by Brookhaven National Laboratory to ensure that body burdens of the exposed Marshallese subjects remained within AEC guidelines. Their body-burden histories and calculated activity ingestion rate patterns post-return are presented along with estimates of internal committed effective dose equivalents. External exposure data are also included. In addition, relationships between body burden or urine-activity concentration and declining continuous intake were developed. The implications of these studies are: (1) the dietary intake of 137Cs was a major component contributing to the committed effective dose equivalent for the years after the initial contamination of the atolls; (2) for persons whose diet included fish, 65Zn was a major component of committed effective dose equivalent during the first years post-return; (3) a decline in the daily activity ingestion rate greater than that resulting from radioactive decay of the source was estimated for 137Cs, 65Zn, 90Sr and 60Co; (4) the relative impact of each nuclide on the estimate of committed effective dose equivalent was dependent upon the time interval between initial contamination and rehabilitation; and (5) the internal committed effective dose equivalent exceeded the external dose equivalent by a factor of 1.1 at Utirik and 1.5 at Rongelap during the rehabitation period. Few reliable 239Pu measurements on human excreta were made. An analysis of the tentative data leads to the conclusion that a reliable estimate of committed effective dose equivalent requires further research.

Measurement equivalence of the German Job Satisfaction Survey used in a multinational organization: implications of Schwartz's culture model.

PubMed

Liu, Cong; Borg, Ingwer; Spector, Paul E

2004-12-01

The authors tested measurement equivalence of the German Job Satisfaction Survey (GJSS) using structural equation modeling methodology. Employees from 18 countries and areas provided data on 5 job satisfaction facets. The effects of language and culture on measurement equivalence were examined. A cultural distance hypothesis, based on S. H. Schwartz's (1999) theory, was tested with 4 cultural groups: West Europe, English speaking, Latin America, and Far East. Findings indicated the robustness of the GJSS in terms of measurement equivalence across countries. The survey maintained high transportability across countries speaking the same language and countries sharing similar cultural backgrounds. Consistent with Schwartz's model, a cultural distance effect on scale transportability among scales used in maximally dissimilar cultures was detected. Scales used in the West Europe group showed greater equivalence to scales used in the English-speaking and Latin America groups than scales used in the Far East group. 2004 APA, all rights reserved

Achieving dynamic switchable filter based on a transmutable metasurface using SMA

NASA Astrophysics Data System (ADS)

Chen, Xin; Gao, Jinsong; Kang, Bonan

2017-09-01

We propose a switchable filter composed of transmutable array using shape memory alloys (SMA). It could exhibit a temperature induced morphology change spontaneously like the biological excitability, acting as a shutter that allows the incident energy to be selectively transmitted or reflected with in excess of 12dB isolation at the certain frequencies for both polarizations. Equivalent circuit models describe the operational principle qualitatively and the switching effect is underpinned by the full-wave analysis. A further physical mechanism is shown by contrasting the distributions of electric field and surface current on the surface at the same frequency for the two working modes. The experimental results consist with the theoretical simulations, indicating that the metasurface could serve as one innovative solution for manipulating the electromagnetic waves and enlighten the next generation of advanced electromagnetic materials with more freedom in the processes of design and manufacturing.

Electrical Counting and Sizing of Mammalian Cells in Suspension

PubMed Central

Gregg, E. C.; Steidley, K. David

1965-01-01

A recently developed method of determining the number and size of particles suspended in a conducting solution is to pump the suspension through a small orifice having an immersed electrode on each side to supply electrical current. The current changes due to the passage of particles of resistivity different from that of the solution. Theoretical expressions are developed which relate the current change caused by such particles to their volume and shape. It is found that most biological cells may be treated as dielectric particles whose capacitive effects are negligible. Electrolytic tank measurements on models confirm the theoretical development, and electric field plots of model orifices are used to predict the observed pulse shapes. An equivalent circuit of the orifice-electrode system is analyzed and shows that the current pulse may be made conductivity-independent when observed with a zero input impedance amplifier. PMID:5861698

[The patents game. Generic and biosimilar drugs].

PubMed

Villamañán, E; González, D; Armada, E; Ruano, M; Álvarez-Sala, R; Herrero, A

2016-01-01

The protection provided by patents on medicines has a limited duration. The expiry of patents expiration allows copies of the drugs to be released, competing with original. At first, they were identical to the original, known as generic drugs, but in recent years, due to the marketing of biological therapies and the expiry of many of their patents, biosimilar drugs have also emerged. These are not exact copies of the original, but, like generic drugs, biosimilar drugs have to demonstrate equivalence to the reference drugs in quality, safety and efficacy. Nevertheless, despite their importance and contribution to sustainability of health system, doctors are sometimes unaware of differences between them, and their impact in terms of clinical and economic effects. An attempt is made to review and clarify certain aspects often unknown by physicians, despite their involvement in their use. Copyright © 2015 SECA. Published by Elsevier Espana. All rights reserved.

Therapeutic ultrasound in physical medicine and rehabilitation: characterization and assessment of its physical effects on joint-mimicking phantoms.

PubMed

Lioce, Elisa Edi Anna Nadia; Novello, Matteo; Durando, Gianni; Bistolfi, Alessandro; Actis, Maria Vittoria; Massazza, Giuseppe; Magnetto, Chiara; Guiot, Caterina

2014-11-01

The aim of the study described here was to quantitatively assess thermal and mechanical effects of therapeutic ultrasound (US) by sonicating a joint-mimicking phantom, made of muscle-equivalent material, using clinical US equipment. The phantom contains two bone disks simulating a deep joint (treated at 1 MHz) and a superficial joint (3 MHz). Thermal probes were inserted in fixed positions. To test the mechanical (cavitational) effects, we used a latex balloon filled with oxygen-loaded nanobubbles; the dimensions of the oxygen-loaded nanobubbles were determined before and after sonication. Significant increases in temperature (up to 17°C) with fixed field using continuous waves were detected both in front of and behind the bones, depending on the US mode (continuous wave vs. pulsed wave) and on the treatment modality (fixed vs. massage). We found no significant differences in mechanical effects. Although limited by the in vitro design (no blood perfusion, no metabolic compensation), the results can be used to guide operators in their choice of the best US treatment modality for a specific joint. Copyright © 2014 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Assessment of the inhibition of ricin toxicity by lactose in milk.

PubMed

Lumor, Stephen E; Deen, Bronwyn D; Ronningen, Ian; Smith, Kenneth; Fredrickson, Neal R; Diez-Gonzalez, Francisco; Labuza, Theodore P

2013-12-01

The effect of lactose at the concentration typically found in milk (134 mM) on the ability of ricin to inhibit protein synthesis in HeLa cells was studied. Ricin (0.001 to 300 μg/ml) that was either not treated or treated with 134 mM lactose was added to test tubes containing 1 ml of HeLa cells (approximately 3 × 10(5) cells in a low-leucine medium). After 2 h of incubation at 37°C, 0.5 μCi of L-[U-(14)C]-leucine was added to each tube and incubated for another 60 min. The cells were harvested by centrifugation and lysed, and cellular proteins were separated. The amount of radioactivity incorporated into the proteins was determined by liquid scintillation. The biological activity of ricin, i. e., the amount of radioactivity in a sample relative to that of the control (cells not treated with ricin), was calculated for each treatment. The inhibitory effect of 134 mM lactose on the biological activity of ricin was only significant at concentrations of ricin below 1 μg/ml. At higher ricin concentrations, the effect of 134 mM lactose decreased as the concentration of ricin increased, resulting in an increase in the inhibition of proteins synthesis. Our results also indicated that bovine milk, when used in place of 134 mM lactose, was more effective for reducing the activity of ricin at concentrations below 1 μg/ml but was ineffective against ricin concentrations greater than 1 μg/ml. These results suggest that milk may not protect against ricin intoxication at the concentration (0.89 μg/ml) equivalent to the lowest limit of its 50 % lethal dose for a 20-kg child consuming 225 ml (8 oz) of milk.

Mutagenicity and in vivo toxicity of combined particulate and semivolatile organic fractions of gasoline and diesel engine emissions.

PubMed

Seagrave, JeanClare; McDonald, Jacob D; Gigliotti, Andrew P; Nikula, Kristen J; Seilkop, Steven K; Gurevich, Michael; Mauderly, Joe L

2002-12-01

Exposure to engine emissions is associated with adverse health effects. However, little is known about the relative effects of emissions produced by different operating conditions, fuels, or technologies. Rapid screening techniques are needed to compare the biological effects of emissions with different characteristics. Here, we examined a set of engine emission samples using conventional bioassays. The samples included combined particulate material and semivolatile organic compound fractions of emissions collected from normal- and high-emitter gasoline and diesel vehicles collected at 72 degrees F, and from normal-emitter groups collected at 30 degrees F. The relative potency of the samples was determined by statistical analysis of the dose-response curves. All samples induced bacterial mutagenicity, with a 10-fold range of potency among the samples. Responses to intratracheal instillation in rats indicated generally parallel rankings of the samples by multiple endpoints reflecting cytotoxic, inflammatory, and lung parenchymal changes, allowing selection of a more limited set of parameters for future studies. The parameters selected to assess oxidative stress and macrophage function yielded little useful information. Responses to instillation indicated little difference in potency per unit of combined particulate material and semivolatile organic compound mass between normal-emitter gasoline and diesel vehicles, or between emissions collected at different temperatures. However, equivalent masses of emissions from high-emitter vehicles of both types were more potent than those from normal-emitters. While preliminary in terms of assessing contributions of different emissions to health hazards, the results indicate that a subset of this panel of assays will be useful in providing rapid, cost-effective feedback on the biological impact of modified technology.

10 CFR 72.106 - Controlled area of an ISFSI or MRS.

Code of Federal Regulations, 2012 CFR

2012-01-01

... controlled area may not receive from any design basis accident the more limiting of a total effective dose equivalent of 0.05 Sv (5 rem), or the sum of the deep-dose equivalent and the committed dose equivalent to any individual organ or tissue (other than the lens of the eye) of 0.5 Sv (50 rem). The lens dose...

10 CFR 72.106 - Controlled area of an ISFSI or MRS.

Code of Federal Regulations, 2014 CFR

2014-01-01

... controlled area may not receive from any design basis accident the more limiting of a total effective dose equivalent of 0.05 Sv (5 rem), or the sum of the deep-dose equivalent and the committed dose equivalent to any individual organ or tissue (other than the lens of the eye) of 0.5 Sv (50 rem). The lens dose...

10 CFR 72.106 - Controlled area of an ISFSI or MRS.

Code of Federal Regulations, 2011 CFR

2011-01-01

... controlled area may not receive from any design basis accident the more limiting of a total effective dose equivalent of 0.05 Sv (5 rem), or the sum of the deep-dose equivalent and the committed dose equivalent to any individual organ or tissue (other than the lens of the eye) of 0.5 Sv (50 rem). The lens dose...

10 CFR 72.106 - Controlled area of an ISFSI or MRS.

Code of Federal Regulations, 2013 CFR

2013-01-01

... controlled area may not receive from any design basis accident the more limiting of a total effective dose equivalent of 0.05 Sv (5 rem), or the sum of the deep-dose equivalent and the committed dose equivalent to any individual organ or tissue (other than the lens of the eye) of 0.5 Sv (50 rem). The lens dose...

10 CFR 72.106 - Controlled area of an ISFSI or MRS.

Code of Federal Regulations, 2010 CFR

2010-01-01

... controlled area may not receive from any design basis accident the more limiting of a total effective dose equivalent of 0.05 Sv (5 rem), or the sum of the deep-dose equivalent and the committed dose equivalent to any individual organ or tissue (other than the lens of the eye) of 0.5 Sv (50 rem). The lens dose...

Effects of a Meaningful, a Discriminative, and a Meaningless Stimulus on Equivalence Class Formation

ERIC Educational Resources Information Center

Fields, Lanny; Arntzen, Erik; Nartey, Richard; Eilifsen, Christoffer

2012-01-01

Thirty college students attempted to form three 3-node 5-member equivalence classes under the simultaneous protocol. After concurrent training of AB, BC, CD, and DE relations, all probes used to assess the emergence of symmetrical, transitive, and equivalence relations were presented for two test blocks. When the A-E stimuli were all abstract…

Effect of Arctic Amplification on Design Snow Loads in Alaska

DTIC Science & Technology

2016-09-01

snow water equivalent UFC Unified Facilities Criteria UTC Coordinated Universal Time Keywords: Alaska, Arctic amplification, climate change...extreme value analysis, snow loads, snow water equivalent , SWE Acknowledgements: This work was conducted with support from the Strategic... equivalent (SWE) of the snowpack. We acquired SWE data from a number of sources that provide automatic or manual observations, reanalysis data, or

Modification of radiobiological effects of 171 MeV protons by elements of physical protection

NASA Astrophysics Data System (ADS)

Bulinina, Taisia; Shurshakov, Vyacheslav; Ivanov, Alexander; Molokanov, Alexander

2016-07-01

Space radiation includes protons of various energies. Physical protection is effective in the case of low energy protons (50-100 MeV) and becomes insufficient for radiation with a high part of high-energy protons. In the experiment performed on outbred mice, the purpose of the study was to evaluate the radiobiological effect of 171 MeV protons and protons modified by elements of physical protection of the spacecraft, on a complex of indicators of the functional condition of the system hematopoiesis and the central nervous system in 24 hours after irradiation at 20 cGy dose. The spacecraft radiation protection elements used in the experiment were a construction of wet hygiene wipes called a «protective curtain», and a glass plate imitating an ISS window. Mass thickness of the " protective curtain" in terms of water equivalent was ̴ 6,2 g/cm2. Physical shielding along the path of 171 MeV protons increases their linear energy transfer leading to the absorbed dose elevation and strengthening of the radiobiological effect. In the experiment, the two types of shielding together raised the absorbed dose from 20 to 23.2 cGy. Chemically different materials (glass and water in the wipes) were found to exert unequal modifying effects on physical and biological parameters of the proton-irradiated mice. There was a distinct dose-dependent reduction of bone marrow cellularity within the dose range from 20 cGy to 23.2 cGy in 24 hours after exposure. No modifying effect of the radiation protection elements on spontaneous motor activity was discovered when compared with entrance protons. The group of animals protected by the glass plate exhibited normal orientative-trying reactions and weakened grip with the forelimbs. The effects observed in the experiment indicate the necessity to carry out comprehensive radiobiological researches (physical, biological and mathematical) in assessing the effects of physical protection, that are actual for ensuring radiation safety of crews in interplanetary flights.

High incidence of micronuclei in lymphocytes from residents of the area near the Semipalatinsk nuclear explosion test site.

PubMed

Tanaka, K; Tchaijunusova, N J; Takatsuji, T; Gusev, B I; Sakerbaev, A K; Hoshi, M; Kamada, N

2000-03-01

The Semipalatinsk area is highly contaminated with radioactive fallout from 40 years of continuous nuclear testing. The biological effects on human health in this area have not been studied. Significant remaining radioactivities include long-lived radioisotopes of 238,239,400Pu, 137Cs and 90Sr. To evaluate the long-term biological effects of the radioactive fallout, the incidence of micronuclei in lymphocytes from residents of the area was observed. Blood was obtained from 10 residents (5 females and 5 males, aged 47 to 55 years old) from each of the 3 areas of Znamenka, Dolon and Semipalatinsk, which are about 50-150 km from the nuclear explosion test site. For micronucleus assay, PHA-stimulated lymphocytes were cultured for 72 h and cytochalasin B was added at 44 h for detecting binuclear lymphocytes. Five thousand binuclear lymphocytes in each resident were scored. The means of micronucleus counts in 1,000 lymphocytes in residents of Semipalatinsk, Dolon and Znamenka were 16.3, 12.6, and 7.80, respectively, which were higher than those of the normal Japanese persons (4.66). These values were equivalent to the results obtained from 0.187-0.47 Gy of chronic exposure to gamma-rays at a dose rate of 0.02 cGy/min. The high incidence of micronuclei in residents of the Semipalatinsk nuclear test site area was mainly caused by internal exposure rather than external exposure received for the past 40 years.

Influence of Porosity on Mechanical Properties and In vivo Response of Ti6Al4V Implants

PubMed Central

Bandyopadhyay, Amit; Espana, Felix; Balla, Vamsi Krishna; Bose, Susmita; Ohgami, Yusuke; Davies, Neal M

2009-01-01

Metallic biomaterials are widely used to restore the lost structure and functions of human bone. Due to the large number of joint replacements, there is a growing demand for new and improved orthopedic implants. More specifically, there is a need for novel load bearing metallic implants with low effective modulus matching to that of bone in order to reduce stress shielding and consequent increase in the in vivo life-span of the implant. In this study, we have fabricated porous Ti6Al4V alloy structures, using Laser Engineered Net Shaping (LENS™) to demonstrate that advanced manufacturing techniques such as LENS™ can be used to fabricate low-modulus, tailored porosity implants with a wide variety of metals/alloys, where the porosity can be designed in areas based on the patient's need to enhance biological fixation and achieve long-term in vivo stability. The effective modulus of Ti6Al4V alloy structures has been tailored between 7 and 60 GPa and porous Ti alloy structures containing 23 to 32 vol. % porosity showed modulus equivalent to human cortical bone. In vivo behavior of porous Ti6Al4V alloy samples in male Sprague-Dawley rats for 16 weeks demonstrated significant increase in calcium within the implants indicating excellent biological tissue ingrowth through interconnected porosity. In vivo results also showed that total amount of porosity plays an important role in tissue ingrowth. PMID:19913643

Establishment of an equivalence acceptance criterion for accelerated stability studies.

PubMed

Burdick, Richard K; Sidor, Leslie

2013-01-01

In this article, the use of statistical equivalence testing for providing evidence of process comparability in an accelerated stability study is advocated over the use of a test of differences. The objective of such a study is to demonstrate comparability by showing that the stability profiles under nonrecommended storage conditions of two processes are equivalent. Because it is difficult at accelerated conditions to find a direct link to product specifications, and hence product safety and efficacy, an equivalence acceptance criterion is proposed that is based on the statistical concept of effect size. As with all statistical tests of equivalence, it is important to collect input from appropriate subject-matter experts when defining the acceptance criterion.

Examination of the equivalence of self-report survey-based paper-and-pencil and internet data collection methods.

PubMed

Weigold, Arne; Weigold, Ingrid K; Russell, Elizabeth J

2013-03-01

Self-report survey-based data collection is increasingly carried out using the Internet, as opposed to the traditional paper-and-pencil method. However, previous research on the equivalence of these methods has yielded inconsistent findings. This may be due to methodological and statistical issues present in much of the literature, such as nonequivalent samples in different conditions due to recruitment, participant self-selection to conditions, and data collection procedures, as well as incomplete or inappropriate statistical procedures for examining equivalence. We conducted 2 studies examining the equivalence of paper-and-pencil and Internet data collection that accounted for these issues. In both studies, we used measures of personality, social desirability, and computer self-efficacy, and, in Study 2, we used personal growth initiative to assess quantitative equivalence (i.e., mean equivalence), qualitative equivalence (i.e., internal consistency and intercorrelations), and auxiliary equivalence (i.e., response rates, missing data, completion time, and comfort completing questionnaires using paper-and-pencil and the Internet). Study 1 investigated the effects of completing surveys via paper-and-pencil or the Internet in both traditional (i.e., lab) and natural (i.e., take-home) settings. Results indicated equivalence across conditions, except for auxiliary equivalence aspects of missing data and completion time. Study 2 examined mailed paper-and-pencil and Internet surveys without contact between experimenter and participants. Results indicated equivalence between conditions, except for auxiliary equivalence aspects of response rate for providing an address and completion time. Overall, the findings show that paper-and-pencil and Internet data collection methods are generally equivalent, particularly for quantitative and qualitative equivalence, with nonequivalence only for some aspects of auxiliary equivalence. PsycINFO Database Record (c) 2013 APA, all rights reserved.

Clinical development of CT-P10 and other biosimilar cancer therapeutics.

PubMed

Kim, Won Seog; Coiffier, Bertrand; Kwon, Hyuk-Chan; Kim, SuYeon

2017-05-01

Biosimilars are highly similar versions of approved biologic drugs that may confer equivalent efficacy at a reduced cost. Patents for several biological cancer therapeutics are past or approaching expiry, presenting an opportunity to increase affordability and global accessibility of key drugs through the development of biosimilars. To receive approval, a biosimilar must show no clinically meaningful differences from the reference product in terms of efficacy or safety. The first monoclonal antibody biosimilar cancer therapeutic to gain approval was CT-P10, a biosimilar of rituximab. Here, we review the oncology clinical development program for CT-P10, providing insights into the rationale for, and design of, CT-P10 clinical trials in patients with cancer. Trials of biosimilar cancer therapeutics in development are also discussed.

Multiple, novel biologically active endophytic actinomycetes isolated from upper Amazonian rainforests.

PubMed

Bascom-Slack, Carol A; Ma, Cong; Moore, Emily; Babbs, Beatrice; Fenn, Kathleen; Greene, Joshua S; Hann, Bradley D; Keehner, Jocelyn; Kelley-Swift, Elizabeth G; Kembaiyan, Vivek; Lee, Sun Jin; Li, Puyao; Light, David Y; Lin, Emily H; Schorn, Michelle A; Vekhter, Daniel; Boulanger, Lori-Ann; Hess, W M; Vargas, Percy Núñez; Strobel, Gary A; Strobel, Scott A

2009-08-01

Microbial biodiversity provides an increasingly important source of medically and industrially useful compounds. We have isolated 14 actinomycete species from a collection of approximately 300 plant stem samples from the upper Amazonian rainforest in Peru. All of the cultured isolates produce substances with inhibitory activity directed at a range of potential fungal and bacterial pathogens. For some organisms, this activity is very broad in spectrum while other organisms show specific activity against a limited number of organisms. Two of these organisms preferentially inhibit bacterial test organisms over eukaryotic organisms. rDNA sequence analysis indicates that these organisms are not equivalent to any other cultured deposits in GenBank. Our results provide evidence of the untapped biodiversity in the form of biologically active microbes present within the tissues of higher plants.

Circadian variations in biologically closed electrochemical circuits in Aloe vera and Mimosa pudica.

PubMed

Volkov, Alexander G; Baker, Kara; Foster, Justin C; Clemmons, Jacqueline; Jovanov, Emil; Markin, Vladislav S

2011-04-01

The circadian clock regulates a wide range of electrophysiological and developmental processes in plants. This paper presents, for the first time, the direct influence of a circadian clock on biologically closed electrochemical circuits in vivo. Here we show circadian variation of the plant responses to electrical stimulation. The biologically closed electrochemical circuits in the leaves of Aloe vera and Mimosa pudica, which regulate their physiology, were analyzed using the charge stimulation method. The electrostimulation was provided with different timing and different voltages. Resistance between Ag/AgCl electrodes in the leaf of Aloe vera was higher during the day than at night. Discharge of the capacitor in Aloe vera at night was faster than during the day. Discharge of the capacitor in a pulvinus of Mimosa pudica was faster during the day. The biologically closed electrical circuits with voltage gated ion channels in Mimosa pudica are also activated the next day, even in the darkness. These results show that the circadian clock can be maintained endogenously and has electrochemical oscillators, which can activate ion channels in biologically closed electrochemical circuits. We present the equivalent electrical circuits in both plants and their circadian variation to explain the experimental data. Copyright © 2011 Elsevier B.V. All rights reserved.

Determination of morphological parameters of biological cells by analysis of scattered-light distributions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Burger, D.E.

1979-11-01

The extraction of morphological parameters from biological cells by analysis of light-scatter patterns is described. A light-scattering measurement system has been designed and constructed that allows one to visually examine and photographically record biological cells or cell models and measure the light-scatter pattern of an individual cell or cell model. Using a laser or conventional illumination, the imaging system consists of a modified microscope with a 35 mm camera attached to record the cell image or light-scatter pattern. Models of biological cells were fabricated. The dynamic range and angular distributions of light scattered from these models was compared to calculatedmore » distributions. Spectrum analysis techniques applied on the light-scatter data give the sought after morphological cell parameters. These results compared favorably to shape parameters of the fabricated cell models confirming the mathematical model procedure. For nucleated biological material, correct nuclear and cell eccentricity as well as the nuclear and cytoplasmic diameters were determined. A method for comparing the flow equivalent of nuclear and cytoplasmic size to the actual dimensions is shown. This light-scattering experiment provides baseline information for automated cytology. In its present application, it involves correlating average size as measured in flow cytology to the actual dimensions determined from this technique. (ERB)« less

BeeSpace Navigator: exploratory analysis of gene function using semantic indexing of biological literature.

PubMed

Sen Sarma, Moushumi; Arcoleo, David; Khetani, Radhika S; Chee, Brant; Ling, Xu; He, Xin; Jiang, Jing; Mei, Qiaozhu; Zhai, ChengXiang; Schatz, Bruce

2011-07-01

With the rapid decrease in cost of genome sequencing, the classification of gene function is becoming a primary problem. Such classification has been performed by human curators who read biological literature to extract evidence. BeeSpace Navigator is a prototype software for exploratory analysis of gene function using biological literature. The software supports an automatic analogue of the curator process to extract functions, with a simple interface intended for all biologists. Since extraction is done on selected collections that are semantically indexed into conceptual spaces, the curation can be task specific. Biological literature containing references to gene lists from expression experiments can be analyzed to extract concepts that are computational equivalents of a classification such as Gene Ontology, yielding discriminating concepts that differentiate gene mentions from other mentions. The functions of individual genes can be summarized from sentences in biological literature, to produce results resembling a model organism database entry that is automatically computed. Statistical frequency analysis based on literature phrase extraction generates offline semantic indexes to support these gene function services. The website with BeeSpace Navigator is free and open to all; there is no login requirement at www.beespace.illinois.edu for version 4. Materials from the 2010 BeeSpace Software Training Workshop are available at www.beespace.illinois.edu/bstwmaterials.php.

Robust synthetic biology design: stochastic game theory approach.

PubMed

Chen, Bor-Sen; Chang, Chia-Hung; Lee, Hsiao-Ching

2009-07-15

Synthetic biology is to engineer artificial biological systems to investigate natural biological phenomena and for a variety of applications. However, the development of synthetic gene networks is still difficult and most newly created gene networks are non-functioning due to uncertain initial conditions and disturbances of extra-cellular environments on the host cell. At present, how to design a robust synthetic gene network to work properly under these uncertain factors is the most important topic of synthetic biology. A robust regulation design is proposed for a stochastic synthetic gene network to achieve the prescribed steady states under these uncertain factors from the minimax regulation perspective. This minimax regulation design problem can be transformed to an equivalent stochastic game problem. Since it is not easy to solve the robust regulation design problem of synthetic gene networks by non-linear stochastic game method directly, the Takagi-Sugeno (T-S) fuzzy model is proposed to approximate the non-linear synthetic gene network via the linear matrix inequality (LMI) technique through the Robust Control Toolbox in Matlab. Finally, an in silico example is given to illustrate the design procedure and to confirm the efficiency and efficacy of the proposed robust gene design method. http://www.ee.nthu.edu.tw/bschen/SyntheticBioDesign_supplement.pdf.

Stochastic noncooperative and cooperative evolutionary game strategies of a population of biological networks under natural selection.

PubMed

Chen, Bor-Sen; Yeh, Chin-Hsun

2017-12-01

We review current static and dynamic evolutionary game strategies of biological networks and discuss the lack of random genetic variations and stochastic environmental disturbances in these models. To include these factors, a population of evolving biological networks is modeled as a nonlinear stochastic biological system with Poisson-driven genetic variations and random environmental fluctuations (stimuli). To gain insight into the evolutionary game theory of stochastic biological networks under natural selection, the phenotypic robustness and network evolvability of noncooperative and cooperative evolutionary game strategies are discussed from a stochastic Nash game perspective. The noncooperative strategy can be transformed into an equivalent multi-objective optimization problem and is shown to display significantly improved network robustness to tolerate genetic variations and buffer environmental disturbances, maintaining phenotypic traits for longer than the cooperative strategy. However, the noncooperative case requires greater effort and more compromises between partly conflicting players. Global linearization is used to simplify the problem of solving nonlinear stochastic evolutionary games. Finally, a simple stochastic evolutionary model of a metabolic pathway is simulated to illustrate the procedure of solving for two evolutionary game strategies and to confirm and compare their respective characteristics in the evolutionary process. Copyright © 2017 Elsevier B.V. All rights reserved.

Changes in Dissolved Organic Matter Composition and Disinfection Byproduct Precursors in Advanced Drinking Water Treatment Processes.

PubMed

Phungsai, Phanwatt; Kurisu, Futoshi; Kasuga, Ikuro; Furumai, Hiroaki

2018-03-20

Molecular changes in dissolved organic matter (DOM) from treatment processes at two drinking water treatment plants in Japan were investigated using unknown screening analysis by Orbitrap mass spectrometry. DOM formulas with carbon, hydrogen and oxygen (CHO-DOM) were the most abundant class in water samples, and over half of them were commonly found at both plants. Among the treatment processes, ozonation induced the most drastic changes to DOM. Mass peak intensities of less saturated CHO-DOM (positive (oxygen subtracted double bond equivalent per carbon (DBE-O)/C)) decreased by ozonation, while more saturated oxidation byproducts (negative (DBE-O)/C) increased and new oxidation byproducts (OBPs) were detected. By Kendrick mass analysis, ozone reactions preferred less saturated CHO-DOM in the same alkylation families and produced more saturated alkylation families of OBPs. Following ozonation, biological activated carbon filtration effectively removed <300 Da CHO-DOM, including OBPs. Following chlorination, over 50 chlorinated formulas of disinfection byproducts (DBPs) were found in chlorinated water samples where at least half were unknown. Putative precursors of these DBPs were determined based on electrophilic substitutions and addition reactions. Ozonation demonstrated better decomposition of addition reaction-type precursors than electrophilic substitution-type precursors; over half of both precursor types decreased during biological activated carbon filtration.

Spatiotemporal radiotherapy planning using a global optimization approach

NASA Astrophysics Data System (ADS)

Adibi, Ali; Salari, Ehsan

2018-02-01

This paper aims at quantifying the extent of potential therapeutic gain, measured using biologically effective dose (BED), that can be achieved by altering the radiation dose distribution over treatment sessions in fractionated radiotherapy. To that end, a spatiotemporally integrated planning approach is developed, where the spatial and temporal dose modulations are optimized simultaneously. The concept of equivalent uniform BED (EUBED) is used to quantify and compare the clinical quality of spatiotemporally heterogeneous dose distributions in target and critical structures. This gives rise to a large-scale non-convex treatment-plan optimization problem, which is solved using global optimization techniques. The proposed spatiotemporal planning approach is tested on two stylized cancer cases resembling two different tumor sites and sensitivity analysis is performed for radio-biological and EUBED parameters. Numerical results validate that spatiotemporal plans are capable of delivering a larger BED to the target volume without increasing the BED in critical structures compared to conventional time-invariant plans. In particular, this additional gain is attributed to the irradiation of different regions of the target volume at different treatment sessions. Additionally, the trade-off between the potential therapeutic gain and the number of distinct dose distributions is quantified, which suggests a diminishing marginal gain as the number of dose distributions increases.

Understanding FRET as a Research Tool for Cellular Studies

PubMed Central

Shrestha, Dilip; Jenei, Attila; Nagy, Péter; Vereb, György; Szöllősi, János

2015-01-01

Communication of molecular species through dynamic association and/or dissociation at various cellular sites governs biological functions. Understanding these physiological processes require delineation of molecular events occurring at the level of individual complexes in a living cell. Among the few non-invasive approaches with nanometer resolution are methods based on Förster Resonance Energy Transfer (FRET). FRET is effective at a distance of 1–10 nm which is equivalent to the size of macromolecules, thus providing an unprecedented level of detail on molecular interactions. The emergence of fluorescent proteins and SNAP- and CLIP- tag proteins provided FRET with the capability to monitor changes in a molecular complex in real-time making it possible to establish the functional significance of the studied molecules in a native environment. Now, FRET is widely used in biological sciences, including the field of proteomics, signal transduction, diagnostics and drug development to address questions almost unimaginable with biochemical methods and conventional microscopies. However, the underlying physics of FRET often scares biologists. Therefore, in this review, our goal is to introduce FRET to non-physicists in a lucid manner. We will also discuss our contributions to various FRET methodologies based on microscopy and flow cytometry, while describing its application for determining the molecular heterogeneity of the plasma membrane in various cell types. PMID:25815593

The damage equivalence of electrons, protons, alphas and gamma rays in rad-hard MOS devices

NASA Technical Reports Server (NTRS)

Stassinopoulos, E. G.; Van Gunten, O.; Brucker, G. J.; Knudson, A. R.; Jordan, T. M.

1983-01-01

This paper reports on a study of damage equivalence in rad-hard MOS devices with 100,000 rads (SiO2) capability. Damage sensitivities for electrons of 1, 2, 3, 5, and 7 MeV, protons of 1, 3, 7, 22, and 40 MeV, 3.4-MeV alphas, and Co-60 gammas were measured and compared. Results indicated that qualitatively the same charge recombination effects occurred in hard oxide devices for doses of 100,000 rads (SiO2) as in soft oxide parts for doses of 1 to 4 krads (SiO2). Consequently, damage equivalency or non-equivalency depended on radiation type and energy. However, recovery effects, both during and after irradiation, controlled relative damage sensitivity and its dependency on total dose, dose rate, supply bias, gate bias, radiation type, and energy. Correction factors can be derived from these data or from similar tests of other hard oxide type, so as to properly evaluate the combined effects of the total space environment.

Relevance and limits of the principle of “equivalence of care” in prison medicine

PubMed Central

Niveau, Gérard

2007-01-01

The principle of “equivalence of care” in prison medicine is a principle by which prison health services are obliged to provide prisoners with care of a quality equivalent to that provided for the general public in the same country. It is cited in numerous national and international directives and recommendations. The principle of equivalence is extremely relevant from the point of view of normative ethics but requires adaptation from the point of view of applied ethics. From a clinical point of view, the principle of equivalence is often insufficient to take account of the adaptations necessary for the organization of care in a correctional setting. The principle of equivalence is cost‐effective in general, but has to be overstepped to ensure the humane management of certain special cases. PMID:17906061

WE-D-BRE-07: Variance-Based Sensitivity Analysis to Quantify the Impact of Biological Uncertainties in Particle Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kamp, F.; Brueningk, S.C.; Wilkens, J.J.

Purpose: In particle therapy, treatment planning and evaluation are frequently based on biological models to estimate the relative biological effectiveness (RBE) or the equivalent dose in 2 Gy fractions (EQD2). In the context of the linear-quadratic model, these quantities depend on biological parameters (α, β) for ions as well as for the reference radiation and on the dose per fraction. The needed biological parameters as well as their dependency on ion species and ion energy typically are subject to large (relative) uncertainties of up to 20–40% or even more. Therefore it is necessary to estimate the resulting uncertainties in e.g.more » RBE or EQD2 caused by the uncertainties of the relevant input parameters. Methods: We use a variance-based sensitivity analysis (SA) approach, in which uncertainties in input parameters are modeled by random number distributions. The evaluated function is executed 10{sup 4} to 10{sup 6} times, each run with a different set of input parameters, randomly varied according to their assigned distribution. The sensitivity S is a variance-based ranking (from S = 0, no impact, to S = 1, only influential part) of the impact of input uncertainties. The SA approach is implemented for carbon ion treatment plans on 3D patient data, providing information about variations (and their origin) in RBE and EQD2. Results: The quantification enables 3D sensitivity maps, showing dependencies of RBE and EQD2 on different input uncertainties. The high number of runs allows displaying the interplay between different input uncertainties. The SA identifies input parameter combinations which result in extreme deviations of the result and the input parameter for which an uncertainty reduction is the most rewarding. Conclusion: The presented variance-based SA provides advantageous properties in terms of visualization and quantification of (biological) uncertainties and their impact. The method is very flexible, model independent, and enables a broad assessment of uncertainties. Supported by DFG grant WI 3745/1-1 and DFG cluster of excellence: Munich-Centre for Advanced Photonics.« less

The Effects of Different Training Structures in the Establishment of Conditional Discriminations and Subsequent Performance on Tests for Stimulus Equivalence

ERIC Educational Resources Information Center

Arntzen, Erik; Grondahl, Terje; Eilifsen, Christoffer

2010-01-01

Previous studies comparing groups of subjects have indicated differential probabilities of stimulus equivalence outcome as a function of training structures. One-to-Many (OTM) and Many-to-One (MTO) training structures seem to produce positive outcomes on tests for stimulus equivalence more often than a Linear Series (LS) training structure does.…

Assessment and quantification of patient set-up errors in nasopharyngeal cancer patients and their biological and dosimetric impact in terms of generalized equivalent uniform dose (gEUD), tumour control probability (TCP) and normal tissue complication probability (NTCP).

PubMed

Boughalia, A; Marcie, S; Fellah, M; Chami, S; Mekki, F

2015-06-01

The aim of this study is to assess and quantify patients' set-up errors using an electronic portal imaging device and to evaluate their dosimetric and biological impact in terms of generalized equivalent uniform dose (gEUD) on predictive models, such as the tumour control probability (TCP) and the normal tissue complication probability (NTCP). 20 patients treated for nasopharyngeal cancer were enrolled in the radiotherapy-oncology department of HCA. Systematic and random errors were quantified. The dosimetric and biological impact of these set-up errors on the target volume and the organ at risk (OARs) coverage were assessed using calculation of dose-volume histogram, gEUD, TCP and NTCP. For this purpose, an in-house software was developed and used. The standard deviations (1SDs) of the systematic set-up and random set-up errors were calculated for the lateral and subclavicular fields and gave the following results: ∑ = 0.63 ± (0.42) mm and σ = 3.75 ± (0.79) mm, respectively. Thus a planning organ at risk volume (PRV) margin of 3 mm was defined around the OARs, and a 5-mm margin used around the clinical target volume. The gEUD, TCP and NTCP calculations obtained with and without set-up errors have shown increased values for tumour, where ΔgEUD (tumour) = 1.94% Gy (p = 0.00721) and ΔTCP = 2.03%. The toxicity of OARs was quantified using gEUD and NTCP. The values of ΔgEUD (OARs) vary from 0.78% to 5.95% in the case of the brainstem and the optic chiasm, respectively. The corresponding ΔNTCP varies from 0.15% to 0.53%, respectively. The quantification of set-up errors has a dosimetric and biological impact on the tumour and on the OARs. The developed in-house software using the concept of gEUD, TCP and NTCP biological models has been successfully used in this study. It can be used also to optimize the treatment plan established for our patients. The gEUD, TCP and NTCP may be more suitable tools to assess the treatment plans before treating the patients.