A comparative study of space radiation organ doses and associated cancer risks using PHITS and HZETRN

NASA Astrophysics Data System (ADS)

Bahadori, Amir A.; Sato, Tatsuhiko; Slaba, Tony C.; Shavers, Mark R.; Semones, Edward J.; Van Baalen, Mary; Bolch, Wesley E.

2013-10-01

NASA currently uses one-dimensional deterministic transport to generate values of the organ dose equivalent needed to calculate stochastic radiation risk following crew space exposures. In this study, organ absorbed doses and dose equivalents are calculated for 50th percentile male and female astronaut phantoms using both the NASA High Charge and Energy Transport Code to perform one-dimensional deterministic transport and the Particle and Heavy Ion Transport Code System to perform three-dimensional Monte Carlo transport. Two measures of radiation risk, effective dose and risk of exposure-induced death (REID) are calculated using the organ dose equivalents resulting from the two methods of radiation transport. For the space radiation environments and simplified shielding configurations considered, small differences (<8%) in the effective dose and REID are found. However, for the galactic cosmic ray (GCR) boundary condition, compensating errors are observed, indicating that comparisons between the integral measurements of complex radiation environments and code calculations can be misleading. Code-to-code benchmarks allow for the comparison of differential quantities, such as secondary particle differential fluence, to provide insight into differences observed in integral quantities for particular components of the GCR spectrum.

Physical basis of radiation protection in space travel

NASA Astrophysics Data System (ADS)

Durante, Marco; Cucinotta, Francis A.

2011-10-01

The health risks of space radiation are arguably the most serious challenge to space exploration, possibly preventing these missions due to safety concerns or increasing their costs to amounts beyond what would be acceptable. Radiation in space is substantially different from Earth: high-energy (E) and charge (Z) particles (HZE) provide the main contribution to the equivalent dose in deep space, whereas γ rays and low-energy α particles are major contributors on Earth. This difference causes a high uncertainty on the estimated radiation health risk (including cancer and noncancer effects), and makes protection extremely difficult. In fact, shielding is very difficult in space: the very high energy of the cosmic rays and the severe mass constraints in spaceflight represent a serious hindrance to effective shielding. Here the physical basis of space radiation protection is described, including the most recent achievements in space radiation transport codes and shielding approaches. Although deterministic and Monte Carlo transport codes can now describe well the interaction of cosmic rays with matter, more accurate double-differential nuclear cross sections are needed to improve the codes. Energy deposition in biological molecules and related effects should also be developed to achieve accurate risk models for long-term exploratory missions. Passive shielding can be effective for solar particle events; however, it is limited for galactic cosmic rays (GCR). Active shielding would have to overcome challenging technical hurdles to protect against GCR. Thus, improved risk assessment and genetic and biomedical approaches are a more likely solution to GCR radiation protection issues.

Cellular track model of biological damage to mammalian cell cultures from galactic cosmic rays

NASA Technical Reports Server (NTRS)

Cucinotta, Francis A.; Katz, Robert; Wilson, John W.; Townsend, Lawrence W.; Nealy, John E.; Shinn, Judy L.

1991-01-01

The assessment of biological damage from the galactic cosmic rays (GCR) is a current interest for exploratory class space missions where the highly ionizing, high-energy, high-charge ions (HZE) particles are the major concern. The relative biological effectiveness (RBE) values determined by ground-based experiments with HZE particles are well described by a parametric track theory of cell inactivation. Using the track model and a deterministic GCR transport code, the biological damage to mammalian cell cultures is considered for 1 year in free space at solar minimum for typical spacecraft shielding. Included are the effects of projectile and target fragmentation. The RBE values for the GCR spectrum which are fluence-dependent in the track model are found to be more severe than the quality factors identified by the International Commission on Radiological Protection publication 26 and seem to obey a simple scaling law with the duration period in free space.

An Improved Analytic Model for Microdosimeter Response

NASA Technical Reports Server (NTRS)

Shinn, Judy L.; Wilson, John W.; Xapsos, Michael A.

2001-01-01

An analytic model used to predict energy deposition fluctuations in a microvolume by ions through direct events is improved to include indirect delta ray events. The new model can now account for the increase in flux at low lineal energy when the ions are of very high energy. Good agreement is obtained between the calculated results and available data for laboratory ion beams. Comparison of GCR (galactic cosmic ray) flux between Shuttle TEPC (tissue equivalent proportional counter) flight data and current calculations draws a different assessment of developmental work required for the GCR transport code (HZETRN) than previously concluded.

Pion and electromagnetic contribution to dose: Comparisons of HZETRN to Monte Carlo results and ISS data

NASA Astrophysics Data System (ADS)

Slaba, Tony C.; Blattnig, Steve R.; Reddell, Brandon; Bahadori, Amir; Norman, Ryan B.; Badavi, Francis F.

2013-07-01

Recent work has indicated that pion production and the associated electromagnetic (EM) cascade may be an important contribution to the total astronaut exposure in space. Recent extensions to the deterministic space radiation transport code, HZETRN, allow the production and transport of pions, muons, electrons, positrons, and photons. In this paper, the extended code is compared to the Monte Carlo codes, Geant4, PHITS, and FLUKA, in slab geometries exposed to galactic cosmic ray (GCR) boundary conditions. While improvements in the HZETRN transport formalism for the new particles are needed, it is shown that reasonable agreement on dose is found at larger shielding thicknesses commonly found on the International Space Station (ISS). Finally, the extended code is compared to ISS data on a minute-by-minute basis over a seven day period in 2001. The impact of pion/EM production on exposure estimates and validation results is clearly shown. The Badhwar-O'Neill (BO) 2004 and 2010 models are used to generate the GCR boundary condition at each time-step allowing the impact of environmental model improvements on validation results to be quantified as well. It is found that the updated BO2010 model noticeably reduces overall exposure estimates from the BO2004 model, and the additional production mechanisms in HZETRN provide some compensation. It is shown that the overestimates provided by the BO2004 GCR model in previous validation studies led to deflated uncertainty estimates for environmental, physics, and transport models, and allowed an important physical interaction (π/EM) to be overlooked in model development. Despite the additional π/EM production mechanisms in HZETRN, a systematic under-prediction of total dose is observed in comparison to Monte Carlo results and measured data.

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.

Time-dependent radiation dose simulations during interplanetary space flights

NASA Astrophysics Data System (ADS)

Dobynde, Mikhail; Shprits, Yuri; Drozdov, Alexander; Hoffman, Jeffrey; Li, Ju

2016-07-01

Space radiation is one of the main concerns in planning long-term interplanetary human space missions. There are two main types of hazardous radiation - Solar Energetic Particles (SEP) and Galactic Cosmic Rays (GCR). Their intensities and evolution depend on the solar activity. GCR activity is most enhanced during solar minimum, while the most intense SEPs usually occur during the solar maximum. SEPs are better shielded with thick shields, while GCR dose is less behind think shields. Time and thickness dependences of the intensity of these two components encourage looking for a time window of flight, when radiation intensity and dose of SEP and GCR would be minimized. In this study we combine state-of-the-art space environment models with GEANT4 simulations to determine the optimal shielding, geometry of the spacecraft, and launch time with respect to the phase of the solar cycle. The radiation environment was described by the time-dependent GCR model, and the SEP spectra that were measured during the period from 1990 to 2010. We included gamma rays, electrons, neutrons and 27 fully ionized elements from hydrogen to nickel. We calculated the astronaut's radiation doses during interplanetary flights using the Monte-Carlo code that accounts for the primary and the secondary radiation. We also performed sensitivity simulations for the assumed spacecraft size and thickness to find an optimal shielding. In conclusion, we present the dependences of the radiation dose as a function of launch date from 1990 to 2010, for flight durations of up to 3 years.

Effects of nuclear cross sections at different energies on the radiation hazard from galactic cosmic rays.

PubMed

Lin, Z W; Adams, J H

2007-03-01

The radiation hazard for astronauts from galactic cosmic rays (GCR) is a major obstacle to long-duration human space exploration. Space radiation transport codes have been developed to calculate the radiation environment on missions to the Moon, Mars, and beyond. We have studied how uncertainties in fragmentation cross sections at different energies affect the accuracy of predictions from such radiation transport calculations. We find that, in deep space, cross sections at energies between 0.3 and 0.85 GeV/nucleon have the largest effect in solar maximum GCR environments. At the International Space Station, cross sections at higher energies have the largest effect due to the geomagnetic cutoff.

Benchmark Analysis of Pion Contribution from Galactic Cosmic Rays

NASA Technical Reports Server (NTRS)

Aghara, Sukesh K.; Blattnig, Steve R.; Norbury, John W.; Singleterry, Robert C., Jr.

2008-01-01

Shielding strategies for extended stays in space must include a comprehensive resolution of the secondary radiation environment inside the spacecraft induced by the primary, external radiation. The distribution of absorbed dose and dose equivalent is a function of the type, energy and population of these secondary products. A systematic verification and validation effort is underway for HZETRN, which is a space radiation transport code currently used by NASA. It performs neutron, proton and heavy ion transport explicitly, but it does not take into account the production and transport of mesons, photons and leptons. The question naturally arises as to what is the contribution of these particles to space radiation. The pion has a production kinetic energy threshold of about 280 MeV. The Galactic cosmic ray (GCR) spectra, coincidentally, reaches flux maxima in the hundreds of MeV range, corresponding to the pion production threshold. We present results from the Monte Carlo code MCNPX, showing the effect of lepton and meson physics when produced and transported explicitly in a GCR environment.

MCNPX Cosmic Ray Shielding Calculations with the NORMAN Phantom Model

NASA Technical Reports Server (NTRS)

James, Michael R.; Durkee, Joe W.; McKinney, Gregg; Singleterry Robert

2008-01-01

The United States is planning manned lunar and interplanetary missions in the coming years. Shielding from cosmic rays is a critical aspect of manned spaceflight. These ventures will present exposure issues involving the interplanetary Galactic Cosmic Ray (GCR) environment. GCRs are comprised primarily of protons (approx.84.5%) and alpha-particles (approx.14.7%), while the remainder is comprised of massive, highly energetic nuclei. The National Aeronautics and Space Administration (NASA) Langley Research Center (LaRC) has commissioned a joint study with Los Alamos National Laboratory (LANL) to investigate the interaction of the GCR environment with humans using high-fidelity, state-of-the-art computer simulations. The simulations involve shielding and dose calculations in order to assess radiation effects in various organs. The simulations are being conducted using high-resolution voxel-phantom models and the MCNPX[1] Monte Carlo radiation-transport code. Recent advances in MCNPX physics packages now enable simulated transport over 2200 types of ions of widely varying energies in large, intricate geometries. We report here initial results obtained using a GCR spectrum and a NORMAN[3] phantom.

Multidimensional representations: The knowledge domain of germs held by students, teachers and medical professionals

NASA Astrophysics Data System (ADS)

Rua, Melissa Jo

The present study examined the understandings held by 5th, 8th, and 11th-grade students, their teachers and medical professionals about germs. Specifically, this study describes the content and structure of students' and adults' conceptions in the areas of germ contraction, transmission, and treatment of infectious and non-infectious diseases caused by microorganisms. Naturalistic and empirical research methods were used to investigate participants' conceptions. Between and within group similarities were found using data from concept maps on the topic "flu," drawings of germs, a 20 word card sort related to germs and illness, and a semi-structured interview. Concept maps were coded according to techniques by Novak and Gowan (1984). Drawings of germs were coded into four main categories (bacteria, viruses, animal cell, other) and five subcategories (disease, caricature, insect, protozoa, unclassified). Cluster patterns for the card sorts of each group were found using multidimensional scaling techniques. Six coding categories emerged from the interview transcripts: (a) transmission, (b) treatment, (c) effect of weather on illness, (d) immune response, (e) location of germs, and (f) similarities and differences between bacteria and viruses. The findings showed students, teachers and medical professionals have different understandings about bacteria and viruses and the structures of those understandings vary. Gaps or holes in the participants knowledge were found in areas such as: (a) how germs are transmitted, (b) where germs are found, (c) how the body transports and uses medicine, (d) how the immune system functions, (e) the difference between vaccines and non-prescription medicines, (f) differences that exist between bacteria and viruses, and (g) bacterial resistance to medication. The youngest students relied heavily upon personal experiences with germs rather than formal instruction when explaining their conceptions. As a result, the influence of media was evident in the students' understandings and images of microbes. Students also viewed germs as a human problem rather than seeing microorganisms as an independent member of the ecosystem. Teachers' explanations about germs varied in explicitness based on the grade level they taught while medical professionals based their understandings on formal knowledge and tended to use explicit technical language in their explanations of the phenomena.

Organization of cytokeratin cytoskeleton and germ plasm in the vegetal cortex of Xenopus laevis oocytes depends on coding and non-coding RNAs: Three-dimensional and ultrastructural analysis

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

Kloc, Malgorzata; Bilinski, Szczepan; Dougherty, Matthew T.

2007-05-01

Recent studies discovered a novel structural role of RNA in maintaining the integrity of the mitotic spindle and cellular cytoskeleton. In Xenopus laevis, non-coding Xlsirts and coding VegT RNAs play a structural role in anchoring localized RNAs, maintaining the organization of the cytokeratin cytoskeleton and germinal granules in the oocyte vegetal cortex and in subsequent development of the germline in the embryo. We studied the ultrastructural effects of antisense oligonucleotide driven ablation of Xlsirts and VegT RNAs on the organization of the cytokeratin, germ plasm and other components of the vegetal cortex. We developed a novel method to immunolabel andmore » visualize cytokeratin at the electron microscopy level, which allowed us to reconstruct the ultrastructural organization of the cytokeratin network relative to the components of the vegetal cortex in Xenopus oocytes. The removal of Xlsirts and VegT RNAs not only disrupts the cytokeratin cytoskeleton but also has a profound transcript-specific effect on the anchoring and distribution of germ plasm islands and their germinal granules and the arrangement of yolk platelets within the vegetal cortex. We suggest that the cytokeratin cytoskeleton plays a role in anchoring of germ plasm islands within the vegetal cortex and germinal granules within the germ plasm islands.« less

Germ-line and somatic EPHA2 coding variants in lens aging and cataract.

PubMed

Bennett, Thomas M; M'Hamdi, Oussama; Hejtmancik, J Fielding; Shiels, Alan

2017-01-01

Rare germ-line mutations in the coding regions of the human EPHA2 gene (EPHA2) have been associated with inherited forms of pediatric cataract, whereas, frequent, non-coding, single nucleotide variants (SNVs) have been associated with age-related cataract. Here we sought to determine if germ-line EPHA2 coding SNVs were associated with age-related cataract in a case-control DNA panel (> 50 years) and if somatic EPHA2 coding SNVs were associated with lens aging and/or cataract in a post-mortem lens DNA panel (> 48 years). Micro-fluidic PCR amplification followed by targeted amplicon (exon) next-generation (deep) sequencing of EPHA2 (17-exons) afforded high read-depth coverage (1000x) for > 82% of reads in the cataract case-control panel (161 cases, 64 controls) and > 70% of reads in the post-mortem lens panel (35 clear lens pairs, 22 cataract lens pairs). Novel and reference (known) missense SNVs in EPHA2 that were predicted in silico to be functionally damaging were found in both cases and controls from the age-related cataract panel at variant allele frequencies (VAFs) consistent with germ-line transmission (VAF > 20%). Similarly, both novel and reference missense SNVs in EPHA2 were found in the post-mortem lens panel at VAFs consistent with a somatic origin (VAF > 3%). The majority of SNVs found in the cataract case-control panel and post-mortem lens panel were transitions and many occurred at di-pyrimidine sites that are susceptible to ultraviolet (UV) radiation induced mutation. These data suggest that novel germ-line (blood) and somatic (lens) coding SNVs in EPHA2 that are predicted to be functionally deleterious occur in adults over 50 years of age. However, both types of EPHA2 coding variants were present at comparable levels in individuals with or without age-related cataract making simple genotype-phenotype correlations inconclusive.

Germ-line and somatic EPHA2 coding variants in lens aging and cataract

PubMed Central

Bennett, Thomas M.; M’Hamdi, Oussama; Hejtmancik, J. Fielding

2017-01-01

Rare germ-line mutations in the coding regions of the human EPHA2 gene (EPHA2) have been associated with inherited forms of pediatric cataract, whereas, frequent, non-coding, single nucleotide variants (SNVs) have been associated with age-related cataract. Here we sought to determine if germ-line EPHA2 coding SNVs were associated with age-related cataract in a case-control DNA panel (> 50 years) and if somatic EPHA2 coding SNVs were associated with lens aging and/or cataract in a post-mortem lens DNA panel (> 48 years). Micro-fluidic PCR amplification followed by targeted amplicon (exon) next-generation (deep) sequencing of EPHA2 (17-exons) afforded high read-depth coverage (1000x) for > 82% of reads in the cataract case-control panel (161 cases, 64 controls) and > 70% of reads in the post-mortem lens panel (35 clear lens pairs, 22 cataract lens pairs). Novel and reference (known) missense SNVs in EPHA2 that were predicted in silico to be functionally damaging were found in both cases and controls from the age-related cataract panel at variant allele frequencies (VAFs) consistent with germ-line transmission (VAF > 20%). Similarly, both novel and reference missense SNVs in EPHA2 were found in the post-mortem lens panel at VAFs consistent with a somatic origin (VAF > 3%). The majority of SNVs found in the cataract case-control panel and post-mortem lens panel were transitions and many occurred at di-pyrimidine sites that are susceptible to ultraviolet (UV) radiation induced mutation. These data suggest that novel germ-line (blood) and somatic (lens) coding SNVs in EPHA2 that are predicted to be functionally deleterious occur in adults over 50 years of age. However, both types of EPHA2 coding variants were present at comparable levels in individuals with or without age-related cataract making simple genotype-phenotype correlations inconclusive. PMID:29267365

Testing the generalized complementary relationship of evaporation with continental-scale long-term water-balance data

NASA Astrophysics Data System (ADS)

Szilagyi, Jozsef; Crago, Richard; Qualls, Russell J.

2016-09-01

The original and revised versions of the generalized complementary relationship (GCR) of evaporation (ET) were tested with six-digit Hydrologic Unit Code (HUC6) level long-term (1981-2010) water-balance data (sample size of 334). The two versions of the GCR were calibrated with Parameter-Elevation Regressions on Independent Slopes Model (PRISM) mean annual precipitation (P) data and validated against water-balance ET (ETwb) as the difference of mean annual HUC6-averaged P and United States Geological Survey HUC6 runoff (Q) rates. The original GCR overestimates P in about 18% of the PRISM grid points covering the contiguous United States in contrast with 12% of the revised version. With HUC6-averaged data the original version has a bias of -25 mm yr-1 vs the revised version's -17 mm yr-1, and it tends to more significantly underestimate ETwb at high values than the revised one (slope of the best fit line is 0.78 vs 0.91). At the same time it slightly outperforms the revised version in terms of the linear correlation coefficient (0.94 vs 0.93) and the root-mean-square error (90 vs 92 mm yr-1).

A Physical Model of Cosmogenic Nuclide Production in Stony and Iron Meteoroids on the Basis of Simulation Experiments

NASA Astrophysics Data System (ADS)

Leya, I.; Lange, H.-J.; Michel, R.; Meltzow, B.; Herpers, U.; Busemann, H.; Wieler, R.; Dittrich-Hannen, B.; Suter, M.; Kubik, P. W.

1995-09-01

By extending and improving earlier model calculations [1-4] of cosmogenic nuclide production by GCR particles in extraterrestrial matter, we can now present a physical model without free parameters for a consistent description of GCR production rates in stony and iron meteoroids. The model takes explicitely into account p and n-induced reactions. GCR 4He particles are considered only approximately. It is based on depth-size and bulk-chemistry-dependent spectra of primary and secondary protons and of secondary neutrons calculated by HET and MORSE codes within the HERMES code system [5] and on the cross sections of the underlying reactions. Comprehensive and reliable sets of proton cross sections from thresholds up to 2.6 GeV exist now for many cosmogenic nuclides (see [6] for a review). For n-induced reactions the situation is not so good. Only a few data at low energies and practically no data at higher energies exist. GCR production of cosmogenic nuclides in stony meteoroids is already dominated by neutron-induced reactions for most meteoroid radii. In iron meteoroids neutrons are even more important because of the high mass numbers of the bulk and of consequently higher multiplicities for production of secondary neutrons. In order to overcome this problem, the necessary excitation functions of neutron-induced reactions were determined from experimental thick-target production rates by least-squares unfolding procedures using the code STAYS'L [7]. The data were produced in laboratory experiments under completely controlled conditions [8-11]. The unfolding procedure starts from guess functions (from threshold up to 900 MeV) based on all available experimental neutron cross sections and on theoretical ones calculated by the AREL [12] code which is a relativistic version of the hybrid model of pre-equilibrium reactions [13]. With the new neutron cross sections it is possible to describe simultanously all data from the simulation experiments with an accuracy of better than 10 % and to calculate consistent cosmogenic nuclide production rates in stony and iron meteoroids. The new model calculations are so far valid for 10Be, 26Al, 36Cl, 41Ca, 53Mn as well as He, Ne and Ar isotopes. The new theoretical production rates are compared with measured depth profiles in stony and iron meteorites and will be discussed with respect to primary GCR spectra and preatmospheric radii and exposure histories of stony and iron meteoroids. Acknowledgement: This work was partially supported by the Deutsche Forschungsgemeinschaft and the Swiss National Science Foundation. References: [1] Michel R. et al. (1991) Meteoritics, 26, 221-242. [2] Michel R. et al. (1995) Planet. Space Sci., in press. [3] Bhandari N. et al. (1993) GCA, 57, 2361-2375. [4] Herpers U. et al. (1995) Planet. Space Sci., in press. [5] Cloth P. et al. (1988) JUEL-2203. [6] Michel R. (1994) in Nuclear Data for Science and Technology (J. K. Dickens, ed.), 337-343, Am. Nucl. Soc., La Grange Park. [7] Perrey F. G. (1977) Code STAYS'L, NEA Data Bank, OECD Paris. [8] Michel R. et al. (1986) Nucl. Instr. Meth. Phys. Res., B16, 61-82. [9] Michel R. et al. (1989) Nucl. Instr. Meth. Phys. Res., B42, 76-100. [10] Michel R. et al. (1993) J. Radioanal. Nucl. Chem., 169, 13-25. [11] Michel R. et al. (1994) in Nuclear Data for Science and Technology (J. K. Dickens, ed.), 377-379, Am. Nucl. Soc., La Grange Park. [12] Blann M. (1994) Code AREL, personal communication to R. Michel. [13] Blann M. (1972) Phys. Rev. Lett., 27, 337-340.

Do Plants Contain G Protein-Coupled Receptors?1[C][W][OPEN

PubMed Central

Taddese, Bruck; Upton, Graham J.G.; Bailey, Gregory R.; Jordan, Siân R.D.; Abdulla, Nuradin Y.; Reeves, Philip J.; Reynolds, Christopher A.

2014-01-01

Whether G protein-coupled receptors (GPCRs) exist in plants is a fundamental biological question. Interest in deorphanizing new GPCRs arises because of their importance in signaling. Within plants, this is controversial, as genome analysis has identified 56 putative GPCRs, including G protein-coupled receptor1 (GCR1), which is reportedly a remote homolog to class A, B, and E GPCRs. Of these, GCR2 is not a GPCR; more recently, it has been proposed that none are, not even GCR1. We have addressed this disparity between genome analysis and biological evidence through a structural bioinformatics study, involving fold recognition methods, from which only GCR1 emerges as a strong candidate. To further probe GCR1, we have developed a novel helix-alignment method, which has been benchmarked against the class A-class B-class F GPCR alignments. In addition, we have presented a mutually consistent set of alignments of GCR1 homologs to class A, class B, and class F GPCRs and shown that GCR1 is closer to class A and/or class B GPCRs than class A, class B, or class F GPCRs are to each other. To further probe GCR1, we have aligned transmembrane helix 3 of GCR1 to each of the six GPCR classes. Variability comparisons provide additional evidence that GCR1 homologs have the GPCR fold. From the alignments and a GCR1 comparative model, we have identified motifs that are common to GCR1, class A, B, and E GPCRs. We discuss the possibilities that emerge from this controversial evidence that GCR1 has a GPCR fold. PMID:24246381

GCR Transport in the Brain: Assessment of Self-Shielding, Columnar Damage, and Nuclear Reactions on Cell Inactivation Rates

NASA Technical Reports Server (NTRS)

Shavers, M. R.; Atwell, W.; Cucinotta, F. A.; Badhwar, G. D. (Technical Monitor)

1999-01-01

Radiation shield design is driven by the need to limit radiation risks while optimizing risk reduction with launch mass/expense penalties. Both limitation and optimization objectives require the development of accurate and complete means for evaluating the effectiveness of various shield materials and body-self shielding. For galactic cosmic rays (GCR), biophysical response models indicate that track structure effects lead to substantially different assessments of shielding effectiveness relative to assessments based on LET-dependent quality factors. Methods for assessing risk to the central nervous system (CNS) from heavy ions are poorly understood at this time. High-energy and charge (HZE) ion can produce tissue events resulting in damage to clusters of cells in a columnar fashion, especially for stopping heavy ions. Grahn (1973) and Todd (1986) have discussed a microlesion concept or model of stochastic tissue events in analyzing damage from HZE's. Some tissues, including the CNS, maybe sensitive to microlesion's or stochastic tissue events in a manner not illuminated by either conventional dosimetry or fluence-based risk factors. HZE ions may also produce important lateral damage to adjacent cells. Fluences of high-energy proton and alpha particles in the GCR are many times higher than HZE ions. Behind spacecraft and body self-shielding the ratio of protons, alpha particles, and neutrons to HZE ions increases several-fold from free-space values. Models of GCR damage behind shielding have placed large concern on the role of target fragments produced from tissue atoms. The self-shielding of the brain reduces the number of heavy ions reaching the interior regions by a large amount and the remaining light particle environment (protons, neutrons, deuterons. and alpha particles) may be the greatest concern. Tracks of high-energy proton produce nuclear reactions in tissue, which can deposit doses of more than 1 Gv within 5 - 10 cell layers. Information on rates of cell killing from GCR, including patterns of cell killing from single particle tracks. can provide useful information on expected differences between proton and HZE tracks and clinical experiences with photon irradiation. To model effects on cells in the brain, it is important that transport models accurately describe changes in the GCR due to interactions in the cranium and proximate tissues. We describe calculations of the attenuated GCR particle fluxes at three dose-points in the brain and associated patterns of cell killing using biophysical models. The effects of the brain self-shielding and bone-tissue interface of the skull in modulating the GCR environment are considered. For each brain dose-point, the mass distribution in the surrounding 4(pi) solid angle is characterized using the CAM model to trace 512 rays. The CAM model describes the self-shielding by converting the tissue distribution to mass-equivalent aluminum, and nominal values of spacecraft shielding is considered. Particle transport is performed with the proton, neutron, and heavy-ion transport code HZETRN with the nuclear fragmentation model QMSFRG. The distribution of cells killed along the path of individual GCR ions is modeled using in vitro cell inactivation data for cells with varying sensitivity. Monte Carlo simulations of arrays of inactivated cells are considered for protons and heavy ions and used to describe the absolute number of cell killing events of various magnitude in the brain from the GCR. Included are simulations of positions of inactivated cells from stopping heavy ions and nuclear stars produced by high-energy ions most importantly, protons and neutrons.

Effects of Nuclear Cross Sections at Different Energies on the Radiation Hazard from Galactic Cosmic Rays

NASA Technical Reports Server (NTRS)

Lin, Z. W.; Adams, J. H., Jr.

2006-01-01

The radiation hazard for astronauts from galactic cosmic rays is a major obstacle in long duration human space explorations. Space radiation transport codes have been developed to calculate radiation environment on missions to the Moon, Mars or beyond. We have studied how uncertainties in fragmentation cross sections at different energies affect the accuracy of predictions from such radiation transport. We find that, in deep space, cross sections between 0.3 and 0.85 GeV/u usually have the largest effect on dose-equivalent behind shielding in solar minimum GCR environments, and cross sections between 0.85 and 1.2 GeV/u have the largest effect in solar maximum GCR environments. At the International Space Station, cross sections at higher energies have the largest effect due to the geomagnetic cutoff.

Estimation of Effective Doses for Radiation Cancer Risks on ISS, Lunar, and Mars Missions with Space Radiation Measurement

NASA Technical Reports Server (NTRS)

Kim, M.Y.; Cucinotta, F.A.

2005-01-01

Radiation protection practices define the effective dose as a weighted sum of equivalent dose over major sites for radiation cancer risks. Since a crew personnel dosimeter does not make direct measurement of effective dose, it has been estimated with skin-dose measurements and radiation transport codes for ISS and STS missions. The Phantom Torso Experiment (PTE) of NASA s Operational Radiation Protection Program has provided the actual flight measurements of active and passive dosimeters which were placed throughout the phantom on STS-91 mission for 10 days and on ISS Increment 2 mission. For the PTE, the variation in organ doses, which is resulted by the absorption and the changes in radiation quality with tissue shielding, was considered by measuring doses at many tissue sites and at several critical body organs including brain, colon, heart, stomach, thyroid, and skins. These measurements have been compared with the organ dose calculations obtained from the transport models. Active TEPC measurements of lineal energy spectra at the surface of the PTE also provided the direct comparison of galactic cosmic ray (GCR) or trapped proton dose and dose equivalent. It is shown that orienting the phantom body as actual in ISS is needed for the direct comparison of the transport models to the ISS data. One of the most important observations for organ dose equivalent of effective dose estimates on ISS is the fractional contribution from trapped protons and GCR. We show that for most organs over 80% is from GCR. The improved estimation of effective doses for radiation cancer risks will be made with the resultant tissue weighting factors and the modified codes.

GCR1, a transcriptional activator in Saccharomyces cerevisiae, complexes with RAP1 and can function without its DNA binding domain.

PubMed Central

Tornow, J; Zeng, X; Gao, W; Santangelo, G M

1993-01-01

In Saccharomyces cerevisiae, efficient expression of glycolytic and translational component genes requires two DNA binding proteins, RAP1 (which binds to UASRPG) and GCR1 (which binds to the CT box). We generated deletions in GCR1 to test the validity of several different models for GCR1 function. We report here that the C-terminal half of GCR1, which includes the domain required for DNA binding to the CT box in vitro, can be removed without affecting GCR1-dependent transcription of either the glycolytic gene ADH1 or the translational component genes TEF1 and TEF2. We have also identified an activation domain within a segment of the GCR1 protein (the N-terminal third) that is essential for in vivo function. RAP1 and GCR1 can be co-immunoprecipitated from whole cell extracts, suggesting that they form a complex in vivo. The data are most consistent with a model in which GCR1 is attracted to DNA through contact with RAP1. Images PMID:8508768

Group C rotavirus infection in patients with acute gastroenteritis in outbreaks in western India between 2006 and 2014.

PubMed

Joshi, M S; Jare, V M; Gopalkrishna, V

2017-01-01

Faecal specimens collected from outbreak (n = 253) and sporadic (n = 147) cases of acute gastroenteritis that occurred in western India between 2006 and 2014 were tested for group C rotavirus (GCR) using partial VP6 gene-based RT-PCR. All specimens were tested previously for the presence of other viral and bacterial aetiological agents by conventional methods. The rate of GCR detection was 8·6% and 0·7% in outbreak and sporadic cases, respectively. GCR infections prevailed in outbreaks reported from rural areas (10·9%) compared to urban areas (1·6%). Clinical severity score of the patients with GCR infection (n = 23) indicated severe disease in the majority (70%) of cases. The age distribution analysis indicated 52·1% of GCR infections in children aged <10 years. The male:female ratio in GCR-positive patients was 2·3:1. Of the 23 GCR-positive cases, 17 (73·9%) had a sole GCR infection and six had mixed infections with other viral and/or bacterial agents. Phylogenetic analysis of nucleotide sequences classified GCR strains of the study in to I2 genotype of the VP6 gene. This is the first study to show the occurrence of GCR in gastroenteritis outbreaks in India.

Distribution of Cytokinin-active Ribonucleosides in Wheat Germ tRNA Species 1

PubMed Central

Struxness, Leslie A.; Armstrong, Donald J.; Gillam, Ian; Tener, Gordon M.; Burrows, William J.; Skoog, Folke

1979-01-01

The distribution of cytokinin activity in wheat (Triticum aestivum) germ tRNA fractionated by BD-cellulose and RPC-5 chromatography has been examined. As in other organisms, the cytokinin moieties in wheat germ tRNA appear to be restricted to tRNA species that would be expected to respond to codons beginning with U. Only a few of the wheat germ tRNA species in this coding group actually contain cytokinin modifications. Cytokinin activity was associated with isoaccepting tRNASer species and with a minor tRNALeu species from wheat germ. All other wheat germ tRNA species corresponding to codons beginning with U were devoid of cytokinin activity in the tobacco callus bioassay. PMID:16660688

Drug Interactions Between Hepatoprotective Agents Ursodeoxycholic Acid or Glycyrrhizin and Ombitasvir/Paritaprevir/Ritonavir in Healthy Japanese Subjects.

PubMed

Zha, Jiuhong; Badri, Prajakta S; Ding, Bifeng; Uchiyama, Naotaka; Alves, Katia; Rodrigues, Lino; Redman, Rebecca; Dutta, Sandeep; Menon, Rajeev M

2015-11-01

The 2 direct-acting antiviral combination (2D) of ombitasvir and paritaprevir (coadministered with ritonavir) is being evaluated for the treatment of chronic hepatitis C virus infection in Japan. Ursodeoxycholic acid (UDCA) and glycyrrhizin (GCR) are hepatoprotective agents widely used in Japan. A drug-drug interaction (DDI) study was conducted to guide dosing recommendations for UDCA and GCR when coadministered with the 2D regimen. DDIs between the 2D regimen (ombitasvir/paritaprevir/ritonavir 25/150/100 mg orally once daily) and UDCA (50 mg orally 3 times daily) or GCR (80 mg intravenously once daily) were evaluated in a 2-arm, multiple-dose study in 24 Japanese healthy subjects under fed conditions. Pharmacokinetic and safety evaluations were performed when UDCA or GCR and the 2D regimen were administered alone and during coadministration. Exposures from coadministration of the 2D regimen plus UDCA or GCR versus the 2D regimen, UDCA, or GCR alone were compared using repeated-measures analyses of natural logarithms of the maximum plasma concentration (Cmax) and area under the curve (AUC). After coadministration of the 2D regimen and UDCA, steady-state exposures (Cmax and AUC) of ombitasvir, paritaprevir, and ritonavir showed a ≤9% change, and UDCA exposures showed a ≤20% change compared with administration alone. When the 2D regimen and GCR were coadministered, steady-state exposures of ombitasvir, paritaprevir, and ritonavir were not affected (≤9% change), GCR AUC increased by 49%, and GCR Cmax was unaffected (<1% change). No dose adjustment is needed for UDCA, GCR, or the 2D regimen when UDCA or GCR is coadministered with the 2D regimen in hepatitis C virus-infected patients under fed conditions. Clinical monitoring of patients using GCR is recommended due to an approximately 50% increase in GCR AUC when coadministered with the 2D regimen. Copyright © 2015 Elsevier HS Journals, Inc. All rights reserved.

openQ*D simulation code for QCD+QED

NASA Astrophysics Data System (ADS)

Campos, Isabel; Fritzsch, Patrick; Hansen, Martin; Krstić Marinković, Marina; Patella, Agostino; Ramos, Alberto; Tantalo, Nazario

2018-03-01

The openQ*D code for the simulation of QCD+QED with C* boundary conditions is presented. This code is based on openQCD-1.6, from which it inherits the core features that ensure its efficiency: the locally-deflated SAP-preconditioned GCR solver, the twisted-mass frequency splitting of the fermion action, the multilevel integrator, the 4th order OMF integrator, the SSE/AVX intrinsics, etc. The photon field is treated as fully dynamical and C* boundary conditions can be chosen in the spatial directions. We discuss the main features of openQ*D, and we show basic test results and performance analysis. An alpha version of this code is publicly available and can be downloaded from http://rcstar.web.cern.ch/.

Model Estimated GCR Particle Flux Variation - Assessment with CRIS Data

NASA Astrophysics Data System (ADS)

Saganti, Premkumar

We present model calculated particle flux as a function of time during the current solar cycle along with the comparisons from the ACE/CRIS data and the Mars/MARIE data. In our model calculations we make use of the NASA's HZETRN (High Z and Energy Transport) code along with the nuclear fragmentation cross sections that are described by the quantum multiple scattering (QMSFRG) model. The time dependant variation of the GCR environment is derived making use of the solar modulation potential, phi. For the past ten years, Advanced Composition Explorer (ACE) has been in orbit at the Sun- Earth libration point (L1). Data from the Cosmic Ray Isotope Spectrometer (CRIS) instrument onboard the ACE spacecraft has been available from 1997 through the present time. Our model calculated particle flux showed high degree of correlation during the earlier phase of the current solar cycle (2003) in the lower Z region within 15

A space radiation shielding model of the Martian radiation environment experiment (MARIE)

NASA Technical Reports Server (NTRS)

Atwell, W.; Saganti, P.; Cucinotta, F. A.; Zeitlin, C. J.

2004-01-01

The 2001 Mars Odyssey spacecraft was launched towards Mars on April 7, 2001. Onboard the spacecraft is the Martian radiation environment experiment (MARIE), which is designed to measure the background radiation environment due to galactic cosmic rays (GCR) and solar protons in the 20-500 MeV/n energy range. We present an approach for developing a space radiation-shielding model of the spacecraft that includes the MARIE instrument in the current mapping phase orientation. A discussion is presented describing the development and methodology used to construct the shielding model. For a given GCR model environment, using the current MARIE shielding model and the high-energy particle transport codes, dose rate values are compared with MARIE measurements during the early mapping phase in Mars orbit. The results show good agreement between the model calculations and the MARIE measurements as presented for the March 2002 dataset. c2003 COSPAR. Published by Elsevier Ltd. All rights reserved.

A space radiation shielding model of the Martian radiationenvironment experiment (MARIE)

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

Atwell, William; Saganti, Premkumar; Cucinotta, Francis A.

2004-12-01

The 2001 Mars Odyssey spacecraft was launched towards Mars on April 7, 2001. On board the spacecraft is the Martian radiation environment experiment (MARIE), which is designed to measure the background radiation environment due to galactic cosmic rays (GCR) and solar protons in the 20 500 MeV/n energy range. We present an approach for developing a space radiation-shielding model of the spacecraft that includes the MARIE instrument in the current mapping phase orientation. A discussion is presented describing the development and methodology used to construct the shielding model. For a given GCR model environment, using the current MARIE shielding modelmore » and the high-energy particle transport codes, dose rate values are compared with MARIE measurements during the early mapping phase in Mars orbit. The results show good agreement between the model calculations and the MARIE measurements as presented for the March 2002 dataset.« less

Electromagnetic Dissociation and Spacecraft Electronics Damage

NASA Technical Reports Server (NTRS)

Norbury, John W.

2016-01-01

When protons or heavy ions from galactic cosmic rays (GCR) or solar particle events (SPE) interact with target nuclei in spacecraft, there can be two different types of interactions. The more familiar strong nuclear interaction often dominates and is responsible for nuclear fragmentation in either the GCR or SPE projectile nucleus or the spacecraft target nucleus. (Of course, the proton does not break up, except possibly to produce pions or other hadrons.) The less familiar, second type of interaction is due to the very strong electromagnetic fields that exist when two charged nuclei pass very close to each other. This process is called electromagnetic dissociation (EMD) and primarily results in the emission of neutrons, protons and light ions (isotopes of hydrogen and helium). The cross section for particle production is approximately defined as the number of particles produced in nucleus-nucleus collisions or other types of reactions. (There are various kinematic and other factors which multiply the particle number to arrive at the cross section.) Strong, nuclear interactions usually dominate the nuclear reactions of most interest that occur between GCR and target nuclei. However, for heavy nuclei (near Fe and beyond) at high energy the EMD cross section can be much larger than the strong nuclear interaction cross section. This paper poses a question: Are there projectile or target nuclei combinations in the interaction of GCR or SPE where the EMD reaction cross section plays a dominant role? If the answer is affirmative, then EMD mechanisms should be an integral part of codes that are used to predict damage to spacecraft electronics. The question can become more fine-tuned and one can ask about total reaction cross sections as compared to double differential cross sections. These issues will be addressed in the present paper.

Forty-four novel protein-coding loci discovered using a proteomics informed by transcriptomics (PIT) approach in rat male germ cells.

PubMed

Chocu, Sophie; Evrard, Bertrand; Lavigne, Régis; Rolland, Antoine D; Aubry, Florence; Jégou, Bernard; Chalmel, Frédéric; Pineau, Charles

2014-11-01

Spermatogenesis is a complex process, dependent upon the successive activation and/or repression of thousands of gene products, and ends with the production of haploid male gametes. RNA sequencing of male germ cells in the rat identified thousands of novel testicular unannotated transcripts (TUTs). Although such RNAs are usually annotated as long noncoding RNAs (lncRNAs), it is possible that some of these TUTs code for protein. To test this possibility, we used a "proteomics informed by transcriptomics" (PIT) strategy combining RNA sequencing data with shotgun proteomics analyses of spermatocytes and spermatids in the rat. Among 3559 TUTs and 506 lncRNAs found in meiotic and postmeiotic germ cells, 44 encoded at least one peptide. We showed that these novel high-confidence protein-coding loci exhibit several genomic features intermediate between those of lncRNAs and mRNAs. We experimentally validated the testicular expression pattern of two of these novel protein-coding gene candidates, both highly conserved in mammals: one for a vesicle-associated membrane protein we named VAMP-9, and the other for an enolase domain-containing protein. This study confirms the potential of PIT approaches for the discovery of protein-coding transcripts initially thought to be untranslated or unknown transcripts. Our results contribute to the understanding of spermatogenesis by characterizing two novel proteins, implicated by their strong expression in germ cells. The mass spectrometry proteomics data have been deposited with the ProteomeXchange Consortium under the data set identifier PXD000872. © 2014 by the Society for the Study of Reproduction, Inc.

Measurement of the cosmic-ray iron spectrum between 60 and 200 GeV per nucleon

NASA Technical Reports Server (NTRS)

Esposito, Joseph A.; Streitmatter, Robert E.; Balasubrahmanyan, V. K.; Ormes, Jonathan F.

1990-01-01

A measurement of the spectral index of Galactic cosmic-ray (GCR) iron has been made using a high-energy gas Cerenkov spectrometer. The spectral index of GCR iron is found to be 2.56 + or - 0.11 in the energy range 57-200 GeV/ nucleon. This result indicates that the source spectrum of GCR iron is similar to that of other primary GCR nuclei and is consistent with the simplest models of GCR propagation.

Transcriptome Analysis of Arabidopsis GCR1 Mutant Reveals Its Roles in Stress, Hormones, Secondary Metabolism and Phosphate Starvation

PubMed Central

Chakraborty, Navjyoti; Sharma, Priyanka; Kanyuka, Kostya; Pathak, Ravi R.; Choudhury, Devapriya; Hooley, Richard A.; Raghuram, Nandula

2015-01-01

The controversy over the existence or the need for G-protein coupled receptors (GPCRs) in plant G-protein signalling has overshadowed a more fundamental quest for the role of AtGCR1, the most studied and often considered the best candidate for GPCR in plants. Our whole transcriptome microarray analysis of the GCR1-knock-out mutant (gcr1-5) in Arabidopsis thaliana revealed 350 differentially expressed genes spanning all chromosomes. Many of them were hitherto unknown in the context of GCR1 or G-protein signalling, such as in phosphate starvation, storage compound and fatty acid biosynthesis, cell fate, etc. We also found some GCR1-responsive genes/processes that are reported to be regulated by heterotrimeric G-proteins, such as biotic and abiotic stress, hormone response and secondary metabolism. Thus, GCR1 could have G-protein-mediated as well as independent roles and regardless of whether it works as a GPCR, further analysis of the organism-wide role of GCR1 has a significance of its own. PMID:25668726

Simulation of Galactic Cosmic Rays and Dose-Rate Effects in RITRACKS

NASA Technical Reports Server (NTRS)

Plante, Ianik; Ponomarev, Artem; Slaba, Tony; Blattnig, Steve; Hada, Megumi

2017-01-01

The NASA Space Radiation Laboratory (NSRL) facility has been used successfully for many years to generate ion beams for radiation research experiments by NASA investigators. Recently, modifications were made to the beam lines to allow rapid switching between different types of ions and energies, with the aim to simulate the Galactic Cosmic Rays (GCR) environment. As this will be a focus of space radiation research for upcoming years, the stochastic radiation track structure code RITRACKS (Relativistic Ion Tracks) was modified to simulate beams of various ion types and energies during time intervals specified by the user at the microscopic and nanoscopic scales. For example, particle distributions of a mixed 344.1-MeV protons (18.04 cGy) and 950-MeV/n iron (5.64 cGy) beam behind a 20 g/cm(exp 2) aluminum followed by a 10 g/cm(exp 2) polyethylene shield as calculated by the code GEANT4 were used as an input field in RITRACKS. Similarly, modifications were also made to simulate a realistic radiation environment in a spacecraft exposed to GCR by sampling the ion types and energies from particle spectra pre-calculated by the code HZETRN. The newly implemented features allows RITRACKS to generate time-dependent differential and cumulative 3D dose voxel maps. These new capabilities of RITRACKS will be used to investigate dose-rate effects and synergistic interactions of various types of radiations for many end points at the microscopic and nanoscopic scales such as DNA damage and chromosome aberrations.

Radiation environment at LEO orbits: MC simulation and experimental data.

NASA Astrophysics Data System (ADS)

Zanini, Alba; Borla, Oscar; Damasso, Mario; Falzetta, Giuseppe

The evaluations of the different components of the radiation environment in spacecraft, both in LEO orbits and in deep space is of great importance because the biological effect on humans and the risk for instrumentation strongly depends on the kind of radiation (high or low LET). That is important especially in view of long term manned or unmanned space missions, (mission to Mars, solar system exploration). The study of space radiation field is extremely complex and not completely solved till today. Given the complexity of the radiation field, an accurate dose evaluation should be considered an indispensable part of any space mission. Two simulation codes (MCNPX and GEANT4) have been used to assess the secondary radiation inside FO-TON M3 satellite and ISS. The energy spectra of primary radiation at LEO orbits have been modelled by using various tools (SPENVIS, OMERE, CREME96) considering separately Van Allen protons, the GCR protons and the GCR alpha particles. This data are used as input for the two MC codes and transported inside the spacecraft. The results of two calculation meth-ods have been compared. Moreover some experimental results previously obtained on FOTON M3 satellite by using TLD, Bubble dosimeter and LIULIN detector are considered to check the performances of the two codes. Finally the same experimental device are at present collecting data on the ISS (ASI experiment BIOKIS -nDOSE) and at the end of the mission the results will be compared with the calculation.

Structure of the mouse glucocorticoid receptor: rapid analysis by size-exclusion high-performance liquid chromatography.

PubMed

LaPointe, M C; Chang, C H; Vedeckis, W V

1986-04-22

Gel-exclusion high-performance liquid chromatography (HPLC) has been used to separate the untransformed from the transformed glucocorticoid receptor (GC-R) extracted from mouse AtT-20 cells. With 200 mM potassium phosphate as the eluent, an efficient separation of the forms of the GC-R is attained in 15-20 min. The untransformed cytosolic GC-R elutes from the column with a Stokes radius (Rs) of 8.2-8.6 nm, as do the molybdate-stabilized GC-R, the purified untransformed GC-R, and the cross-linked cytosolic GC-R. GC-R transformed in vitro by either ammonium sulfate precipitation, KCl treatment, or G-25 chromatography elutes with an Rs of 5.7-6 nm. Also, GC-R extracted from the nucleus with either 0.3 M KCl or 2 mM sodium tungstate, or purified by two cycles of DNA-cellulose chromatography, has an Rs of 5.5-6.3 nm. The data are identical either in the presence or in the absence of 20 mM Na2MoO4, suggesting that molybdate is not causing aggregation to produce a larger Rs value than that of the native receptor. Vertical tube rotor sucrose gradient ultracentrifugation of cytosol produces three forms of the GC-R: 9.1 S, 5.2 S, and 3.8 S. Sequential analysis of the GC-R forms by HPLC and vertical tube rotor ultracentrifugation and vice versa allows for the hydrodynamic determination of molecular weight within a very short time period (2-3 h total).(ABSTRACT TRUNCATED AT 250 WORDS)

International Collaboration for Galactic Cosmic Ray Simulation at the NASA Space Radiation Laboratory

NASA Technical Reports Server (NTRS)

Norbury, John W.; Slaba, Tony C.; Rusek, Adam; Durante, Marco; Reitz, Guenther

2015-01-01

An international collaboration on Galactic Cosmic Ray (GCR) simulation is being formed to make recommendations on how to best simulate the GCR spectrum at ground based accelerators. The external GCR spectrum is significantly modified when it passes through spacecraft shielding and astronauts. One approach for simulating the GCR space radiation environment at ground based accelerators would use the modified spectrum, rather than the external spectrum, in the accelerator beams impinging on biological targets. Two recent workshops have studied such GCR simulation. The first workshop was held at NASA Langley Research Center in October 2014. The second workshop was held at the NASA Space Radiation Investigators' workshop in Galveston, Texas in January 2015. The anticipated outcome of these and other studies may be a report or journal article, written by an international collaboration, making accelerator beam recommendations for GCR simulation. This poster describes the status of GCR simulation at the NASA Space Radiation Laboratory and encourages others to join the collaboration.

An Analytical Model for the Prediction of a Micro-Dosimeter Response Function

NASA Technical Reports Server (NTRS)

Badavi, Francis F.; Xapsos, Mike

2008-01-01

A rapid analytical procedure for the prediction of a micro-dosimeter response function in low Earth orbit (LEO), correlated with the Space Transportation System (STS, shuttle) Tissue Equivalent Proportional Counter (TEPC) measurements is presented. The analytical model takes into consideration the energy loss straggling and chord length distribution of the detector, and is capable of predicting energy deposition fluctuations in a cylindrical micro-volume of arbitrary aspect ratio (height/diameter) by incoming ions through both direct and indirect (ray) events. At any designated (ray traced) target point within the vehicle, the model accepts the differential flux spectrum of Galactic Cosmic Rays (GCR) and/or trapped protons at LEO as input. On a desktop PC, the response function of TEPC for each ion in the GCR/trapped field is computed at the average rate of 30 seconds/ion. The ionizing radiation environment at LEO is represented by O'Neill fs GCR model (2004), covering charged particles in the 1 less than or equal to Z less than or equal to 28. O'Neill's free space GCR model is coupled with the Langley Research Center (LaRC) angular dependent geomagnetic cutoff model to compute the transmission coefficient in LEO. The trapped proton environment is represented by a LaRC developed time dependent procedure which couples the AP8MIN/AP8MAX, Deep River Neutron Monitor (DRNM) and F10.7 solar radio frequency measurements. The albedo neutron environment is represented by the extrapolation of the Atmospheric Ionizing Radiation (AIR) measurements. The charged particle transport calculations correlated with STS 51 and 114 flights are accomplished by using the most recent version (2005) of the LaRC deterministic High charge (Z) and Energy TRaNsport (HZETRN) code. We present the correlations between the TEPC model predictions (response function) and TEPC measured differential/integral spectra in the lineal energy (y) domain for both GCR and trapped protons, with the conclusion that the model correctly accounts for the increase in flux at low y values where energetic ions are the primary contributor. We further discuss that, even with the incorporation of angular dependency in the cutoffs, comparison of the GCR differential/integral flux between STS 51 and 114 TEPC measured data and current calculations indicates that there still exists an underestimation by the simulations at low to mid range y values. This underestimation is partly related the exclusion of the secondary pion particle production from the current version of HZETRN.

Monte Carlo transport model comparison with 1A GeV accelerated iron experiment: heavy-ion shielding evaluation of NASA space flight-crew foodstuff

NASA Astrophysics Data System (ADS)

Stephens, D. L.; Townsend, L. W.; Miller, J.; Zeitlin, C.; Heilbronn, L.

Deep-space manned flight as a reality depends on a viable solution to the radiation problem. Both acute and chronic radiation health threats are known to exist, with solar particle events as an example of the former and galactic cosmic rays (GCR) of the latter. In this experiment Iron ions of 1A GeV are used to simulate GCR and to determine the secondary radiation field created as the GCR-like particles interact with a thick target. A NASA prepared food pantry locker was subjected to the iron beam and the secondary fluence recorded. A modified version of the Monte Carlo heavy ion transport code developed by Zeitlin at LBNL is compared with experimental fluence. The foodstuff is modeled as mixed nuts as defined by the 71 st edition of the Chemical Rubber Company (CRC) Handbook of Physics and Chemistry. The results indicate a good agreement between the experimental data and the model. The agreement between model and experiment is determined using a linear fit to ordered pairs of data. The intercept is forced to zero. The slope fit is 0.825 and the R 2 value is 0.429 over the resolved fluence region. The removal of an outlier, Z=14, gives values of 0.888 and 0.705 for slope and R 2 respectively.

Efficient transcription of the glycolytic gene ADH1 and three translational component genes requires the GCR1 product, which can act through TUF/GRF/RAP binding sites.

PubMed Central

Santangelo, G M; Tornow, J

1990-01-01

Glycolytic gene expression in Saccharomyces cerevisiae is thought to be activated by the GCR and TUF proteins. We tested the hypothesis that GCR function is mediated by TUF/GRF/RAP binding sites (UASRPG elements). We found that UASRPG-dependent activation of a heterologous gene and transcription of ADH1, TEF1, TEF2, and RP59 were sensitive to GCR1 disruption. GCR is not required for TUF/GRF/RAP expression or in vitro DNA-binding activity. Images PMID:2405258

Real Distribution of the Coronal Green Line Intensity and Modelling Study of Galactic Cosmic Ray Propagation

NASA Astrophysics Data System (ADS)

Gushchina, R. T.; Alania, M. V.; Gil, A.; Iskra, K.; Siluszyk, M.

2003-07-01

transport equation of galactic cosmic rays (GCR) has been numerically solved for different qA>0 (1996) and qA<0 (1987) epochs assuming that free path of GCR scattering in the interplanetary space is controlled by the Sun's coronal green line intensity (CGLI). We found some distinctions in the distribution of the expected heliolatitudinal gradients of GCR for two and three dimensional interplanetary magnetic field. INTRODUCTION. modulation of GCR in the interplanetary space is generally determined by four processesdiffusion, convection, drift and energy change of GCR particles due to interaction with the solar wind. The joint effect of all above mentioned processes result the 11year variation of GCR. In papers [1-3] are assumed that the general reason of the 11-year variation of GCR in the energy range more than 1 GeV is different structure of the irregularities of the IMF in the maxima and minima epochs of solar activity (SA) caused the radical changes of the dependence of diffusion coefficient on the rigidity of GCR particles. EXPERIMENTAL DATA AND METHOD OF INVESTIGATION. experimental data of sunspot numbers, sunspots' areas and CGLI (λ = 5303˚) show a considerable changes during the 11-year cycle of SA, while e.g. A the changes of the solar wind velocity are not so noticeable [4, 5]. An attempt to take into account influences of the real distributions of the sunspot's areas and the Sun's CGLI on the modulation of GCR considering delay time of the phenomena in the interplanetary space with respect to the processes on the Sun have been undertaken in papers [6-8]. One of parameters of SA contentiously observed on the Earth is the Sun's CGLI. One can suppose that a modulation of GCR by some means is controlled by the changes of the CGLI; particularly there is assumed that a scattering free path of GCR transport is related with the

Malignant pineal germ-cell tumors: an analysis of cases from three tumor registries.

PubMed

Villano, J Lee; Propp, Jennifer M; Porter, Kimberly R; Stewart, Andrew K; Valyi-Nagy, Tibor; Li, Xinyu; Engelhard, Herbert H; McCarthy, Bridget J

2008-04-01

The exact incidence of pineal germ-cell tumors is largely unknown. The tumors are rare, and the number of patients with these tumors, as reported in clinical series, has been limited. The goal of this study was to describe pineal germ-cell tumors in a large number of patients, using data from available brain tumor databases. Three different databases were used: Surveillance, Epidemiology, and End Results (SEER) database (1973-2001); Central Brain Tumor Registry of the United States (CBTRUS; 1997-2001); and National Cancer Data Base (NCDB; 1985-2003). Tumors were identified using the International Classification of Diseases for Oncology, third edition (ICD-O-3), site code C75.3, and categorized according to histology codes 9060-9085. Data were analyzed using SAS/STAT release 8.2, SEER*Stat version 5.2, and SPSS version 13.0 software. A total of 1,467 cases of malignant pineal germ-cell tumors were identified: 1,159 from NCDB, 196 from SEER, and 112 from CBTRUS. All three databases showed a male predominance for pineal germ-cell tumors (>90%), and >72% of patients were Caucasian. The peak number of cases occurred in the 10- to 14-year age group in the CBTRUS data and in the 15- to 19-year age group in the SEER and NCDB data, and declined significantly thereafter. The majority of tumors (73%-86%) were germinomas, and patients with germinomas had the highest survival rate (>79% at 5 years). Most patients were treated with surgical resection and radiation therapy or with radiation therapy alone. The number of patients included in this study exceeds that of any study published to date. The proportions of malignant pineal germ-cell tumors and intracranial germ-cell tumors are in range with previous studies. Survival rates for malignant pineal germ-cell tumors are lower than results from recent treatment trials for intracranial germ-cell tumors, and patients that received radiation therapy in the treatment plan either with surgery or alone survived the longest.

Comparison of Organ Dosimetry for Astronaut Phantoms: Earth-Based vs. Microgravity-Based Anthropometry and Body Positioning

NASA Technical Reports Server (NTRS)

VanBaalen, Mary; Bahadon, Amir; Shavers, Mark; Semones, Edward

2011-01-01

The purpose of this study is to use NASA radiation transport codes to compare astronaut organ dose equivalents resulting from solar particle events (SPE), geomagnetically trapped protons, and free-space galactic cosmic rays (GCR) using phantom models representing Earth-based and microgravity-based anthropometry and positioning. Methods: The Univer sity of Florida hybrid adult phantoms were scaled to represent male and female astronauts with 5th, 50th, and 95th percentile heights and weights as measured on Earth. Another set of scaled phantoms, incorporating microgravity-induced changes, such as spinal lengthening, leg volume loss, and the assumption of the neutral body position, was also created. A ray-tracer was created and used to generate body self-shielding distributions for dose points within a voxelized phantom under isotropic irradiation conditions, which closely approximates the free-space radiation environment. Simplified external shielding consisting of an aluminum spherical shell was used to consider the influence of a spacesuit or shielding of a hull. These distributions were combined with depth dose distributions generated from the NASA radiation transport codes BRYNTRN (SPE and trapped protons) and HZETRN (GCR) to yield dose equivalent. Many points were sampled per organ. Results: The organ dos e equivalent rates were on the order of 1.5-2.5 mSv per day for GCR (1977 solar minimum) and 0.4-0.8 mSv per day for trapped proton irradiation with shielding of 2 g cm-2 aluminum equivalent. The organ dose equivalents for SPE irradiation varied considerably, with the skin and eye lens having the highest organ dose equivalents and deep-seated organs, such as the bladder, liver, and stomach having the lowest. Conclus ions: The greatest differences between the Earth-based and microgravity-based phantoms are observed for smaller ray thicknesses, since the most drastic changes involved limb repositioning and not overall phantom size. Improved self-shielding models reduce the overall uncertainty in organ dosimetry for mission-risk projections and assessments for astronauts

Low Clouds and Cosmic Rays: Possible Reasons for Correlation Changes

NASA Astrophysics Data System (ADS)

Veretenenko, S. V.; Ogurtsov, M. G.

2015-03-01

In this work we investigated the nature of correlations between low cloud cover anomalies (LCA) and galactic cosmic ray (GCR) variations detected on the decadal time scale, as well as possible reasons for the violation of these correlations in the early 2000s. It was shown that the link between cloud cover at middle latitudes and GCR fluxes is not direct, but it is realized through GCR influence on the development of extratropical baric systems (cyclones and troughs) which form cloud field. As the sign of GCR effects on the troposphere dynamics seems to depend on the strength of the stratospheric polar vortex, a possible reason for the violation of a positive correlation between LCA and GCR fluxes in the early 2000s may be the change of the vortex state which resulted in the reversal of GCR effects on extratropical cyclone development.

Light ion components of the galactic cosmic rays: Nuclear interactions and transport theory

NASA Technical Reports Server (NTRS)

Cucinotta, F. A.; Townsend, L. W.; Wilson, J. W.; Shinn, J. L.; Badhwar, G. D.; Dubey, R. R.

1996-01-01

Light nuclei are present in the primary galactic cosmic rays (GCR) and are produced in thick targets due to projectile or target fragmentation from both nucleon and heavy induced reactions. In the primary GCR, He-4 is the most abundant nucleus after H-1. However, there are also a substantial fluxes of H-2 and He-3. In this paper we describe theoretical models based on quantum multiple scattering theory for the description of light ion nuclear interactions. The energy dependence of the light ion fragmentation cross section is considered with comparisons of inclusive yields and secondary momentum distributions to experiments described. We also analyze the importance of a fast component of lights ions from proton and neutron induced target fragementation. These theoretical models have been incorporated into the cosmic ray transport code HZETRN and will be used to analyze the role of shielding materials in modulating the production and the energy spectrum of light ions.

Galactic Cosmic Ray Event-Based Risk Model (GERM) Code

NASA Technical Reports Server (NTRS)

Cucinotta, Francis A.; Plante, Ianik; Ponomarev, Artem L.; Kim, Myung-Hee Y.

2013-01-01

This software describes the transport and energy deposition of the passage of galactic cosmic rays in astronaut tissues during space travel, or heavy ion beams in patients in cancer therapy. Space radiation risk is a probability distribution, and time-dependent biological events must be accounted for physical description of space radiation transport in tissues and cells. A stochastic model can calculate the probability density directly without unverified assumptions about shape of probability density function. The prior art of transport codes calculates the average flux and dose of particles behind spacecraft and tissue shielding. Because of the signaling times for activation and relaxation in the cell and tissue, transport code must describe temporal and microspatial density of functions to correlate DNA and oxidative damage with non-targeted effects of signals, bystander, etc. These are absolutely ignored or impossible in the prior art. The GERM code provides scientists data interpretation of experiments; modeling of beam line, shielding of target samples, and sample holders; and estimation of basic physical and biological outputs of their experiments. For mono-energetic ion beams, basic physical and biological properties are calculated for a selected ion type, such as kinetic energy, mass, charge number, absorbed dose, or fluence. Evaluated quantities are linear energy transfer (LET), range (R), absorption and fragmentation cross-sections, and the probability of nuclear interactions after 1 or 5 cm of water equivalent material. In addition, a set of biophysical properties is evaluated, such as the Poisson distribution for a specified cellular area, cell survival curves, and DNA damage yields per cell. Also, the GERM code calculates the radiation transport of the beam line for either a fixed number of user-specified depths or at multiple positions along the Bragg curve of the particle in a selected material. The GERM code makes the numerical estimates of basic physical and biophysical quantities of high-energy protons and heavy ions that have been studied at the NASA Space Radiation Laboratory (NSRL) for the purpose of simulating space radiation biological effects. In the first option, properties of monoenergetic beams are treated. In the second option, the transport of beams in different materials is treated. Similar biophysical properties as in the first option are evaluated for the primary ion and its secondary particles. Additional properties related to the nuclear fragmentation of the beam are evaluated. The GERM code is a computationally efficient Monte-Carlo heavy-ion-beam model. It includes accurate models of LET, range, residual energy, and straggling, and the quantum multiple scattering fragmentation (QMSGRG) nuclear database.

Comparisons of Integrated Radiation Transport Models with Microdosimetry Data in Spaceflight

NASA Technical Reports Server (NTRS)

Cucinotta, Francis A.; Nikjoo, H.; Kim, M. Y.; Hu, X.; Dicello, J. F.; Pisacane, V. L.

2006-01-01

Astronauts are exposed to galactic cosmic rays (GCR), trapped protons, and possible solar particle events (SPE) during spaceflight. For such complicated mixtures of radiation types and kinetic energies, tissue equivalent proportional counters (TEPC's) represent a simple time-dependent approach for radiation monitoring. Of interest in radiation protection is the average quality factor of a radiation field defined as a function of linear energy transfer, LET, Q(sub ave)(LET). However TEPC's measure the average quality factors as a function of lineal energy (y), Q(sub ave)(y) defined as the average energy deposition in a volume divided by the average chord length of the volume. Lineal energy, y deviates from LET due to energy straggling, delta-ray escape or entry, and nuclear fragments produced in the detector. Using integrated space radiation models that includes the transport code HZETRN/BRYNTRN, the quantum nuclear interaction model, QMSFRG, and results from Monte-Carlo track simulations of TEPC's response to ions, we consider comparisons of model calculations to TEPC results from NASA missions in low Earth orbit and make predictions for lunar and Mars missions. Good agreement between the model and measured spectra from past NASA missions is found. A finding of this work is that TEPC's values for trapped or solar protons of Q(sub ave)(y) range from 1.9-2.5, overestimating Q(sub ave)(LET), which ranges from 1.4-1.6 with both quantities increasing with shielding depth due to nuclear secondaries Comparisons for the complete GCR spectra show that Q(sub ave)(LET) for GCR is approximately 3.5-4.5, while TEPC's measure 2.9-3.4 for Q(sub ave)(y) with the GCR values decreasing with depth as heavy ions are absorbed in shielding material. Our results support the use of TEPC's for space radiation environmental monitoring when computational analysis is used for proper data interpretation.

Lymphocyte senescence in COPD is associated with loss of glucocorticoid receptor expression by pro-inflammatory/cytotoxic lymphocytes.

PubMed

Hodge, Greg; Jersmann, Hubertus; Tran, Hai B; Holmes, Mark; Reynolds, Paul N; Hodge, Sandra

2015-01-09

Glucocorticoid (GC) resistance is a major barrier in COPD treatment. We have shown increased expression of the drug efflux pump, Pgp1 in cytotoxic/pro-inflammatory lymphocytes in COPD. Loss of lymphocyte co-stimulatory molecule CD28 (lymphocyte senescence) was associated with a further increase in their pro-inflammatory/cytotoxic potential and resistance to GC. We hypothesized that lymphocyte senescence and increased Pgp1 are also associated with down-regulation of the GC receptor (GCR). Blood was collected from 10 COPD and 10 healthy aged-matched controls. Flow cytometry was applied to assess intracellular pro-inflammatory cytokines, CD28, Pgp1, GCR, steroid binding and relative cytoplasm/nuclear GCR by CD28+ and CD28null T, NKT-like cells. GCR localization was confirmed by fluorescent microscopy. COPD was associated with increased numbers of CD28nullCD8+ T and NKT-like cells. Loss of CD28 was associated with an increased percentage of T and NKT-like cells producing IFNγ or TNFα and associated with a loss of GCR and Dex-Fluor staining but unchanged Pgp1. There was a significant loss of GCR in CD8 + CD28null compared with CD8 + CD28+ T and NKT-like cells from both COPD and controls (eg, mean ± SEM 8 ± 3% GCR + CD8 + CD28null T-cells vs 49 ± 5% GCR + CD8 + CD28+ T-cells in COPD). There was a significant negative correlation between GCR expression and IFNγ and TNFα production by T and NKT-like cells(eg, COPD: T-cell IFNγ R = -.615; ) and with FEV1 in COPD (R = -.777). COPD is associated with loss of GCR in senescent CD28null and NKT-like cells suggesting alternative treatment options to GC are required to inhibit these pro-inflammatory/cytotoxic cells.

Galactic Cosmic Ray Simulator at the NASA Space Radiation Laboratory

NASA Technical Reports Server (NTRS)

Norbury, John W.; Slaba, Tony C.; Rusek, Adam

2015-01-01

The external Galactic Cosmic Ray (GCR) spectrum is significantly modified when it passes through spacecraft shielding and astronauts. One approach for simulating the GCR space radiation environment is to attempt to reproduce the unmodified, external GCR spectrum at a ground based accelerator. A possibly better approach would use the modified, shielded tissue spectrum, to select accelerator beams impinging on biological targets. NASA plans for implementation of a GCR simulator at the NASA Space Radiation Laboratory (NSRL) at Brookhaven National Laboratory will be discussed.

GCR Environmental Models III: GCR Model Validation and Propagated Uncertainties in Effective Dose

NASA Technical Reports Server (NTRS)

Slaba, Tony C.; Xu, Xiaojing; Blattnig, Steve R.; Norman, Ryan B.

2014-01-01

This is the last of three papers focused on quantifying the uncertainty associated with galactic cosmic rays (GCR) models used for space radiation shielding applications. In the first paper, it was found that GCR ions with Z>2 and boundary energy below 500 MeV/nucleon induce less than 5% of the total effective dose behind shielding. This is an important finding since GCR model development and validation have been heavily biased toward Advanced Composition Explorer/Cosmic Ray Isotope Spectrometer measurements below 500 MeV/nucleon. Weights were also developed that quantify the relative contribution of defined GCR energy and charge groups to effective dose behind shielding. In the second paper, it was shown that these weights could be used to efficiently propagate GCR model uncertainties into effective dose behind shielding. In this work, uncertainties are quantified for a few commonly used GCR models. A validation metric is developed that accounts for measurements uncertainty, and the metric is coupled to the fast uncertainty propagation method. For this work, the Badhwar-O'Neill (BON) 2010 and 2011 and the Matthia GCR models are compared to an extensive measurement database. It is shown that BON2011 systematically overestimates heavy ion fluxes in the range 0.5-4 GeV/nucleon. The BON2010 and BON2011 also show moderate and large errors in reproducing past solar activity near the 2000 solar maximum and 2010 solar minimum. It is found that all three models induce relative errors in effective dose in the interval [-20%, 20%] at a 68% confidence level. The BON2010 and Matthia models are found to have similar overall uncertainty estimates and are preferred for space radiation shielding applications.

Solar activity, the QBO, and tropospheric responses

NASA Technical Reports Server (NTRS)

Tinsley, Brian A.; Brown, Geoffrey M.; Scherrer, Philip H.

1989-01-01

The suggestion that galactic cosmic rays (GCR) as modulated by the solar wind are the carriers of the component of solar variability that affects weather and climate has been discussed in the literature for 30 years, and there is now a considerable body of evidence that supports it. Variations of GCR occur with the 11 year solar cycle, matching the time scale of recent results for atmospheric variations, as modulated by the quasibiennial oscillation of equatorial stratospheric winds (the QBO). Variations in GCR occur on the time scale of centuries with a well defined peak in the coldest decade of the little ice age. New evidence is presented on the meteorological responses to GCR variations on the time scale of a few days. These responses include changes in the vertical temperature profile in the troposphere and lower stratosphere in the two days following solar flare related high speed plasma streams and associated GCR decreases, and in decreases in Vorticity Area Index (VAI) following Forbush decreases of GCR. The occurrence of correlations of GCR and meteorological responses on all three time scales strengthens the hypothesis of GCR as carriers of solar variability to the lower atmosphere. Both short and long term tropospheric responses are understandable as changes in the intensity of cyclonic storms initiated by mechanisms involving cloud microphysical and cloud electrification processes, due to changes in local ion production from changes in GCR fluxes and other high energy particles in the MeV to low GeV range. The nature of these mechanisms remains undetermined. Possible stratospheric wind (particularly QBO) effects on the transport of HNO3 and other constituents incorporated in cluster ions and possible condensation and freezing nuclei are considered as relevant to the long term variations.

Operational Prototype Development of a Global Aircraft Radiation Exposure Nowcast

NASA Astrophysics Data System (ADS)

Mertens, Christopher; Kress, Brian; Wiltberger, Michael; Tobiska, W. Kent; Bouwer, Dave

Galactic cosmic rays (GCR) and solar energetic particles (SEP) are the primary sources of human exposure to high linear energy transfer (LET) radiation in the atmosphere. High-LET radiation is effective at directly breaking DNA strands in biological tissue, or producing chemically active radicals in tissue that alter the cell function, both of which can lead to cancer or other adverse health effects. A prototype operational nowcast model of air-crew radiation exposure is currently under development and funded by NASA. The model predicts air-crew radiation exposure levels from both GCR and SEP that may accompany solar storms. The new air-crew radiation exposure model is called the Nowcast of Atmospheric Ionizing Radiation for Aviation Safety (NAIRAS) model. NAIRAS will provide global, data-driven, real-time exposure predictions of biologically harmful radiation at aviation altitudes. Observations are utilized from the ground (neutron monitors), from the atmosphere (the NCEP Global Forecast System), and from space (NASA/ACE and NOAA/GOES). Atmospheric observations characterize the overhead mass shielding and the ground-and space-based observations provide boundary conditions on the incident GCR and SEP particle flux distributions for transport and dosimetry calculations. Radiation exposure rates are calculated using the NASA physics-based HZETRN (High Charge (Z) and Energy TRaNsport) code. An overview of the NAIRAS model is given: the concept, design, prototype implementation status, data access, and example results. Issues encountered thus far and known and/or anticipated hurdles to research to operations transition are also discussed.

Monte Carlo transport model comparison with 1A GeV accelerated iron experiment: heavy-ion shielding evaluation of NASA space flight-crew foodstuff

NASA Technical Reports Server (NTRS)

Stephens, D. L. Jr; Townsend, L. W.; Miller, J.; Zeitlin, C.; Heilbronn, L.

2002-01-01

Deep-space manned flight as a reality depends on a viable solution to the radiation problem. Both acute and chronic radiation health threats are known to exist, with solar particle events as an example of the former and galactic cosmic rays (GCR) of the latter. In this experiment Iron ions of 1A GeV are used to simulate GCR and to determine the secondary radiation field created as the GCR-like particles interact with a thick target. A NASA prepared food pantry locker was subjected to the iron beam and the secondary fluence recorded. A modified version of the Monte Carlo heavy ion transport code developed by Zeitlin at LBNL is compared with experimental fluence. The foodstuff is modeled as mixed nuts as defined by the 71st edition of the Chemical Rubber Company (CRC) Handbook of Physics and Chemistry. The results indicate a good agreement between the experimental data and the model. The agreement between model and experiment is determined using a linear fit to ordered pairs of data. The intercept is forced to zero. The slope fit is 0.825 and the R2 value is 0.429 over the resolved fluence region. The removal of an outlier, Z=14, gives values of 0.888 and 0.705 for slope and R2 respectively. c2002 COSPAR. Published by Elsevier Science Ltd. All rights reserved.

Monte Carlo transport model comparison with 1A GeV accelerated iron experiment: heavy-ion shielding evaluation of NASA space flight-crew foodstuff.

PubMed

Stephens, D L; Townsend, L W; Miller, J; Zeitlin, C; Heilbronn, L

2002-01-01

Deep-space manned flight as a reality depends on a viable solution to the radiation problem. Both acute and chronic radiation health threats are known to exist, with solar particle events as an example of the former and galactic cosmic rays (GCR) of the latter. In this experiment Iron ions of 1A GeV are used to simulate GCR and to determine the secondary radiation field created as the GCR-like particles interact with a thick target. A NASA prepared food pantry locker was subjected to the iron beam and the secondary fluence recorded. A modified version of the Monte Carlo heavy ion transport code developed by Zeitlin at LBNL is compared with experimental fluence. The foodstuff is modeled as mixed nuts as defined by the 71st edition of the Chemical Rubber Company (CRC) Handbook of Physics and Chemistry. The results indicate a good agreement between the experimental data and the model. The agreement between model and experiment is determined using a linear fit to ordered pairs of data. The intercept is forced to zero. The slope fit is 0.825 and the R2 value is 0.429 over the resolved fluence region. The removal of an outlier, Z=14, gives values of 0.888 and 0.705 for slope and R2 respectively. c2002 COSPAR. Published by Elsevier Science Ltd. All rights reserved.

Use of Apollo 17 Epoch Neutron Spectrum as a Benchmark in Testing LEND Collimated Sensor

NASA Technical Reports Server (NTRS)

Chin, Gordon; Sagdeev, R.; Milikh, G.

2011-01-01

The Apollo 17 neutron experiment LPNE provided a unique set of data on production of neutrons in the Lunar soil bombarded by Galactic Cosmic Rays (GCR). It serves as valuable "ground-truth" in the age of orbital remote sensing. We used the neutron data attributed to Apollo 17 epoch as a benchmark for testing the LEND's collimated sensor, as introduced by the geometry of collimator and efficiency of He3 counters. The latter is defined by the size of gas counter and pressure inside it. The intensity and energy spectrum of neutrons escaping the lunar surface are dependent on incident flux of Galactic Cosmic Rays (GCR) whose variability is associated with Solar Cycle and its peculiarities. We obtain first the share of neutrons entering through the field of view of collimator as a fraction of the total neutron flux by using the angular distribution of neutron exiting the Moon described by our Monte Carlo code. We computed next the count rate of the 3He sensor by using the neutron energy spectrum from McKinney et al. [JGR, 2006] and by consider geometry and gas pressure of the LEND sensor. Finally the neutron count rate obtained for the Apollo 17 epoch characterized by intermediate solar activity was adjusted to the LRO epoch characterized by low solar activity. It has been done by taking into account solar modulation potential, which affects the GCR flux, and in turn changes the neutron albedo flux.

NASA Galactic Cosmic Radiation Environment Model: Badhwar - O'Neill (2014)

NASA Technical Reports Server (NTRS)

Golge, S.; O'Neill, P. M.; Slaba, T. C.

2015-01-01

The Badhwar-O'Neill (BON) Galactic Cosmic Ray (GCR) flux model has been used by NASA to certify microelectronic systems and in the analysis of radiation health risks for human space flight missions. Of special interest to NASA is the kinetic energy region below 4.0 GeV/n due to the fact that exposure from GCR behind shielding (e.g., inside a space vehicle) is heavily influenced by the GCR particles from this energy domain. The BON model numerically solves the Fokker-Planck differential equation to account for particle transport in the heliosphere due to diffusion, convection, and adiabatic deceleration under the assumption of a spherically symmetric heliosphere. The model utilizes a comprehensive database of GCR measurements from various particle detectors to determine boundary conditions. By using an updated GCR database and improved model fit parameters, the new BON model (BON14) is significantly improved over the previous BON models for describing the GCR radiation environment of interest to human space flight.

NASA Galactic Cosmic Radiation Environment Model: Badhwar-O'Neill (2014)

NASA Technical Reports Server (NTRS)

O'Neill, P. M.; Golge, S.; Slaba, T. C.

2015-01-01

The Badhwar-O'Neill (BON) Galactic Cosmic Ray (GCR) flux model is used by NASA to certify microelectronic systems and in the analysis of radiation health risks for human space flight missions. Of special interest to NASA is the kinetic energy region below 4.0 GeV/n due to the fact that exposure from GCR behind shielding (e.g., inside a space vehicle) is heavily influenced by the GCR particles from this energy domain. The BON model numerically solves the Fokker-Planck differential equation to account for particle transport in the heliosphere due to diffusion, convection, and adiabatic deceleration under the assumption of a spherically symmetric heliosphere. The model utilizes a GCR measurements database from various particle detectors to determine the boundary conditions. By using an updated GCR database and improved model fit parameters, the new BON model (BON14) is significantly improved over the previous BON models for describing the GCR radiation environment of interest to human space flight.

The boron-to-beryllium ratio in halo stars - A signature of cosmic-ray nucleosynthesis in the early Galaxy

NASA Technical Reports Server (NTRS)

Walker, T. P.; Steigman, G.; Schramm, D. N.; Olive, K. A.; Fields, B.

1993-01-01

We discuss Galactic cosmic-ray (GCR) spallation production of Li, Be, and B in the early Galaxy with particular attention to the uncertainties in the predictions of this model. The observed correlation between the Be abundance and the metallicity in metal-poor Population II stars requires that Be was synthesized in the early Galaxy. We show that the observations and such Population II GCR synthesis of Be are quantitatively consistent with the big bang nucleosynthesis production of Li-7. We find that there is a nearly model independent lower bound to B/Be of about 7 for GCR synthesis. Recent measurements of B/Be about 10 in HD 140283 are in excellent agreement with the predictions of Population II GCR nucleosynthesis. Measurements of the boron abundance in additional metal-poor halo stars is a key diagnostic of the GCR spallation mechanism. We also show that Population II GCR synthesis can produce amounts of Li-6 which may be observed in the hottest halo stars.

Validity of the Aluminum Equivalent Approximation in Space Radiation Shielding

NASA Technical Reports Server (NTRS)

Badavi, Francis F.; Adams, Daniel O.; Wilson, John W.

2009-01-01

The origin of the aluminum equivalent shield approximation in space radiation analysis can be traced back to its roots in the early years of the NASA space programs (Mercury, Gemini and Apollo) wherein the primary radiobiological concern was the intense sources of ionizing radiation causing short term effects which was thought to jeopardize the safety of the crew and hence the mission. Herein, it is shown that the aluminum equivalent shield approximation, although reasonably well suited for that time period and to the application for which it was developed, is of questionable usefulness to the radiobiological concerns of routine space operations of the 21 st century which will include long stays onboard the International Space Station (ISS) and perhaps the moon. This is especially true for a risk based protection system, as appears imminent for deep space exploration where the long-term effects of Galactic Cosmic Ray (GCR) exposure is of primary concern. The present analysis demonstrates that sufficiently large errors in the interior particle environment of a spacecraft result from the use of the aluminum equivalent approximation, and such approximations should be avoided in future astronaut risk estimates. In this study, the aluminum equivalent approximation is evaluated as a means for estimating the particle environment within a spacecraft structure induced by the GCR radiation field. For comparison, the two extremes of the GCR environment, the 1977 solar minimum and the 2001 solar maximum, are considered. These environments are coupled to the Langley Research Center (LaRC) deterministic ionized particle transport code High charge (Z) and Energy TRaNsport (HZETRN), which propagates the GCR spectra for elements with charges (Z) in the range I <= Z <= 28 (H -- Ni) and secondary neutrons through selected target materials. The coupling of the GCR extremes to HZETRN allows for the examination of the induced environment within the interior' of an idealized spacecraft as approximated by a spherical shell shield, and the effects of the aluminum equivalent approximation for a good polymeric shield material such as genetic polyethylene (PE). The shield thickness is represented by a 25 g/cm spherical shell. Although one could imagine the progression to greater thickness, the current range will be sufficient to evaluate the qualitative usefulness of the aluminum equivalent approximation. Upon establishing the inaccuracies of the aluminum equivalent approximation through numerical simulations of the GCR radiation field attenuation for PE and aluminum equivalent PE spherical shells, we Anther present results for a limited set of commercially available, hydrogen rich, multifunctional polymeric constituents to assess the effect of the aluminum equivalent approximation on their radiation attenuation response as compared to the generic PE.

Early Results from the Advanced Radiation Protection Thick GCR Shielding Project

NASA Technical Reports Server (NTRS)

Norman, Ryan B.; Clowdsley, Martha; Slaba, Tony; Heilbronn, Lawrence; Zeitlin, Cary; Kenny, Sean; Crespo, Luis; Giesy, Daniel; Warner, James; McGirl, Natalie;

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.

Assessment and Requirements of Nuclear Reaction Databases for GCR Transport in the Atmosphere and Structures

NASA Technical Reports Server (NTRS)

Cucinotta, F. A.; Wilson, J. W.; Shinn, J. L.; Tripathi, R. K.

1998-01-01

The transport properties of galactic cosmic rays (GCR) in the atmosphere, material structures, and human body (self-shielding) am of interest in risk assessment for supersonic and subsonic aircraft and for space travel in low-Earth orbit and on interplanetary missions. Nuclear reactions, such as knockout and fragmentation, present large modifications of particle type and energies of the galactic cosmic rays in penetrating materials. We make an assessment of the current nuclear reaction models and improvements in these model for developing required transport code data bases. A new fragmentation data base (QMSFRG) based on microscopic models is compared to the NUCFRG2 model and implications for shield assessment made using the HZETRN radiation transport code. For deep penetration problems, the build-up of light particles, such as nucleons, light clusters and mesons from nuclear reactions in conjunction with the absorption of the heavy ions, leads to the dominance of the charge Z = 0, 1, and 2 hadrons in the exposures at large penetration depths. Light particles are produced through nuclear or cluster knockout and in evaporation events with characteristically distinct spectra which play unique roles in the build-up of secondary radiation's in shielding. We describe models of light particle production in nucleon and heavy ion induced reactions and make an assessment of the importance of light particle multiplicity and spectral parameters in these exposures.

Impact of AMS-02 Measurements on Reducing GCR Model Uncertainties

NASA Technical Reports Server (NTRS)

Slaba, T. C.; O'Neill, P. M.; Golge, S.; Norbury, J. W.

2015-01-01

For vehicle design, shield optimization, mission planning, and astronaut risk assessment, the exposure from galactic cosmic rays (GCR) poses a significant and complex problem both in low Earth orbit and in deep space. To address this problem, various computational tools have been developed to quantify the exposure and risk in a wide range of scenarios. Generally, the tool used to describe the ambient GCR environment provides the input into subsequent computational tools and is therefore a critical component of end-to-end procedures. Over the past few years, several researchers have independently and very carefully compared some of the widely used GCR models to more rigorously characterize model differences and quantify uncertainties. All of the GCR models studied rely heavily on calibrating to available near-Earth measurements of GCR particle energy spectra, typically over restricted energy regions and short time periods. In this work, we first review recent sensitivity studies quantifying the ions and energies in the ambient GCR environment of greatest importance to exposure quantities behind shielding. Currently available measurements used to calibrate and validate GCR models are also summarized within this context. It is shown that the AMS-II measurements will fill a critically important gap in the measurement database. The emergence of AMS-II measurements also provides a unique opportunity to validate existing models against measurements that were not used to calibrate free parameters in the empirical descriptions. Discussion is given regarding rigorous approaches to implement the independent validation efforts, followed by recalibration of empirical parameters.

Cosmogenic-nuclide production by primary cosmic-ray protons

NASA Technical Reports Server (NTRS)

Reedy, R. C.

1985-01-01

The production rates of cosmogenic nuclides were calculated for the primary protons in the galactic and solar cosmic rays. At 1 AU, the long-term average fluxes of solar protons usually produce many more atoms of cosmogenic nuclide than the primary protons in the galactic cosmic rays (GCR). Because the particle fluxes inside meteorites and other large objects in space include many secondary neutrons, the production rates and ratios inside large objects are often very different from those by just the primary GCR protons. It is possible to determine if a small object, was small in space or broken from a meteorite. Because heliospherical modulation and other interactions change the GCR particle spectrum, the production of cosmogenic nuclides by the GCR particles outside the heliosphere will be different from that by modulated GCR primaries.

Effect of Aluminum Alloying on the Hot Deformation Behavior of Nano-bainite Bearing Steel

NASA Astrophysics Data System (ADS)

Yang, Z. N.; Dai, L. Q.; Chu, C. H.; Zhang, F. C.; Wang, L. W.; Xiao, A. P.

2017-12-01

Interest in using aluminum in nano-bainite steel, especially for high-carbon bearing steel, is gradually growing. In this study, GCr15SiMo and GCr15SiMoAl steels are introduced to investigate the effect of Al alloying on the hot deformation behavior of bearing steel. Results show that the addition of Al not only notably increases the flow stress of steel due to the strong strengthening effect of Al on austenite phase, but also accelerates the strain-softening rates for its increasing effect on stacking fault energy. Al alloying also increases the activation energy of deformation. Two constitutive equations with an accuracy of higher than 0.99 are proposed. The constructed processing maps show the expanded instability regions for GCr15SiMoAl steel as compared with GCr15SiMo steel. This finding is consistent with the occurrence of cracking on the GCr15SiMoAl specimens, revealing that Al alloying reduces the high-temperature plasticity of the bearing steel. On the contrary, GCr15SiMoAl steel possesses smaller grain size than GCr15SiMo steel, manifesting the positive effect of Al on bearing steel. Attention should be focused on the hot working process of bearing steel with Al.

Practical Applications of Cosmic Ray Science: Spacecraft, Aircraft, Ground-Based Computation and Control Systems, Exploration, and Human Health and Safety

NASA Technical Reports Server (NTRS)

Koontz, Steve

2015-01-01

In this presentation a review of galactic cosmic ray (GCR) effects on microelectronic systems and human health and safety is given. The methods used to evaluate and mitigate unwanted cosmic ray effects in ground-based, atmospheric flight, and space flight environments are also reviewed. However not all GCR effects are undesirable. We will also briefly review how observation and analysis of GCR interactions with planetary atmospheres and surfaces and reveal important compositional and geophysical data on earth and elsewhere. About 1000 GCR particles enter every square meter of Earth’s upper atmosphere every second, roughly the same number striking every square meter of the International Space Station (ISS) and every other low- Earth orbit spacecraft. GCR particles are high energy ionized atomic nuclei (90% protons, 9% alpha particles, 1% heavier nuclei) traveling very close to the speed of light. The GCR particle flux is even higher in interplanetary space because the geomagnetic field provides some limited magnetic shielding. Collisions of GCR particles with atomic nuclei in planetary atmospheres and/or regolith as well as spacecraft materials produce nuclear reactions and energetic/highly penetrating secondary particle showers. Three twentieth century technology developments have driven an ongoing evolution of basic cosmic ray science into a set of practical engineering tools needed to design, test, and verify the safety and reliability of modern complex technological systems and assess effects on human health and safety effects. The key technology developments are: 1) high altitude commercial and military aircraft; 2) manned and unmanned spacecraft; and 3) increasingly complex and sensitive solid state micro-electronics systems. Space and geophysical exploration needs drove the development of the instruments and analytical tools needed to recover compositional and structural data from GCR induced nuclear reactions and secondary particle showers. Finally, the possible role of GCR secondary particle showers in addressing an important homeland security problem, finding nuclear contraband and weapons, will be briefly reviewed.

Dose calculations at high altitudes and in deep space with GEANT4 using BIC and JQMD models for nucleus nucleus reactions

NASA Astrophysics Data System (ADS)

Sihver, L.; Matthiä, D.; Koi, T.; Mancusi, D.

2008-10-01

Radiation exposure of aircrew is more and more recognized as an occupational hazard. The ionizing environment at standard commercial aircraft flight altitudes consists mainly of secondary particles, of which the neutrons give a major contribution to the dose equivalent. Accurate estimations of neutron spectra in the atmosphere are therefore essential for correct calculations of aircrew doses. Energetic solar particle events (SPE) could also lead to significantly increased dose rates, especially at routes close to the North Pole, e.g. for flights between Europe and USA. It is also well known that the radiation environment encountered by personnel aboard low Earth orbit (LEO) spacecraft or aboard a spacecraft traveling outside the Earth's protective magnetosphere is much harsher compared with that within the atmosphere since the personnel are exposed to radiation from both galactic cosmic rays (GCR) and SPE. The relative contribution to the dose from GCR when traveling outside the Earth's magnetosphere, e.g. to the Moon or Mars, is even greater, and reliable and accurate particle and heavy ion transport codes are essential to calculate the radiation risks for both aircrew and personnel on spacecraft. We have therefore performed calculations of neutron distributions in the atmosphere, total dose equivalents, and quality factors at different depths in a water sphere in an imaginary spacecraft during solar minimum in a geosynchronous orbit. The calculations were performed with the GEANT4 Monte Carlo (MC) code using both the binary cascade (BIC) model, which is part of the standard GEANT4 package, and the JQMD model, which is used in the particle and heavy ion transport code PHITS GEANT4.

Rates for neutron-capture reactions on tungsten isotopes in iron meteorites. [Abstract only

NASA Technical Reports Server (NTRS)

Masarik, J.; Reedy, R. C.

1994-01-01

High-precision W isotopic analyses by Harper and Jacobsen indicate the W-182/W-183 ratio in the Toluca iron meteorite is shifted by -(3.0 +/- 0.9) x 10(exp -4) relative to a terrestrial standard. Possible causes of this shift are neutron-capture reactions on W during Toluca's approximately 600-Ma exposure to cosmic ray particles or radiogenic growth of W-182 from 9-Ma Hf-182 in the silicate portion of the Earth after removal of W to the Earth's core. Calculations for the rates of neutron-capture reactions on W isotopes were done to study the first possibility. The LAHET Code System (LCS) which consists of the Los Alamos High Energy Transport (LAHET) code and the Monte Carlo N-Particle(MCNP) transport code was used to numerically simulate the irradiation of the Toluca iron meteorite by galactic-cosmic-ray (GCR) particles and to calculate the rates of W(n, gamma) reactions. Toluca was modeled as a 3.9-m-radius sphere with the composition of a typical IA iron meteorite. The incident GCR protons and their interactions were modeled with LAHET, which also handled the interactions of neutrons with energies above 20 MeV. The rates for the capture of neutrons by W-182, W-183, and W-186 were calculated using the detailed library of (n, gamma) cross sections in MCNP. For this study of the possible effect of W(n, gamma) reactions on W isotope systematics, we consider the peak rates. The calculated maximum change in the normalized W-182/W-183 ratio due to neutron-capture reactions cannot account for more than 25% of the mass 182 deficit observed in Toluca W.

Unigenic Evolution: A Novel Genetic Method Localizes a Putative Leucine Zipper That Mediates Dimerization of the Saccharomyces Cerevisiae Regulator Gcr1p

PubMed Central

Deminoff, S. J.; Tornow, J.; Santangelo, G. M.

1995-01-01

The GCR1 gene of Saccharomyces cerevisiae encodes a transcriptional activator that complexes with Rap1p and, through UAS(RPG) elements (Rap1p DNA binding sites), stimulates efficient expression of glycolytic and translational component genes. To map the functionally important domains in Gcr1p, we combined multiple rounds of random mutagenesis in vitro with in vivo selection of functional genes to locate conserved, or hypomutable, regions. We name this method unigenic evolution, a statistical analysis of mutations in evolutionary variants of a single gene in an otherwise isogenic background. Examination of the distribution of 315 mutations in 24 variant alleles allowed the localization of four hypomutable regions in GCR1 (A, B, C, and D). Dispensable N-terminal (intronic) and C-terminal portions of the evolved region of GCR1 were included in the analysis as controls and were, as expected, not hypomutable. The analysis of several insertion, deletion, and point mutations, combined with a comparison of the hypomutability and hydrophobicity plots of Gcr1p, suggested that some of the hypomutable regions may individually or in combination correspond to functionally important surface domains. In particular, we determined that region D contains a putative leucine zipper and is necessary and sufficient for Gcr1p homodimerization. PMID:8601472

Peculiarities of cosmic ray modulation in the solar minimum 23/24

NASA Astrophysics Data System (ADS)

Alania, M. V.; Modzelewska, R.; Wawrzynczak, A.

2014-06-01

We study changes of the galactic cosmic ray (GCR) intensity for the ending period of the solar cycle 23 and the beginning of the solar cycle 24 using neutron monitors experimental data. We show that an increase of the GCR intensity in 2009 is generally related with decrease of the solar wind velocity U, the strength B of the interplanetary magnetic field (IMF), and the drift in negative (A < 0) polarity epoch. We present that temporal changes of rigidity dependence of the GCR intensity variation, before reaching maximum level in 2009 and after it, do not noticeably differ from each other. The rigidity spectrum of the GCR intensity variations calculated based on neutron monitors data (for rigidities > 10 GV) is hard in the minimum and near-minimum epoch. We do not recognize any nonordinary changes in the physical mechanism of modulation of the GCR intensity in the rigidity range of GCR particles to which neutron monitors respond. We compose 2-D nonstationary model of transport equation to describe variations of the GCR intensity for 1996-2012 including the A > 0 (1996-2001) and the A < 0 (2002-2012) periods; diffusion coefficient of cosmic rays for rigidity 10-15 GV is increased by 30% in 2009 (A < 0) comparing with 1996 (A > 0). We believe that the proposed model is relatively realistic, and obtained results are satisfactorily compatible with neutron monitors data.

Novel Accurate Bacterial Discrimination by MALDI-Time-of-Flight MS Based on Ribosomal Proteins Coding in S10-spc-alpha Operon at Strain Level S10-GERMS

NASA Astrophysics Data System (ADS)

Tamura, Hiroto; Hotta, Yudai; Sato, Hiroaki

2013-08-01

Matrix-assisted laser-desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) is one of the most widely used mass-based approaches for bacterial identification and classification because of the simple sample preparation and extremely rapid analysis within a few minutes. To establish the accurate MALDI-TOF MS bacterial discrimination method at strain level, the ribosomal subunit proteins coded in the S 10-spc-alpha operon, which encodes half of the ribosomal subunit protein and is highly conserved in eubacterial genomes, were selected as reliable biomarkers. This method, named the S10-GERMS method, revealed that the strains of genus Pseudomonas were successfully identified and discriminated at species and strain levels, respectively; therefore, the S10-GERMS method was further applied to discriminate the pathovar of P. syringae. The eight selected biomarkers (L24, L30, S10, S12, S14, S16, S17, and S19) suggested the rapid discrimination of P. syringae at the strain (pathovar) level. The S10-GERMS method appears to be a powerful tool for rapid and reliable bacterial discrimination and successful phylogenetic characterization. In this article, an overview of the utilization of results from the S10-GERMS method is presented, highlighting the characterization of the Lactobacillus casei group and discrimination of the bacteria of genera Bacillus and Sphingopyxis despite only two and one base difference in the 16S rRNA gene sequence, respectively.

GCR Modulation by Small-Scale Features in the Interplanetary Medium

NASA Astrophysics Data System (ADS)

Jordan, A. P.; Spence, H. E.; Blake, J. B.; Mulligan, T. L.; Shaul, D. N.; Galametz, M.

2007-12-01

In an effort to uncover the properties of structures in the interplanetary medium (IPM) that modulate galactic cosmic rays (GCR) on short time-scales (from hours to days), we study periods of differing conditions in the IPM. We analyze GCR variations from spacecraft both inside and outside the magnetosphere, using the High Sensitivity Telescope (HIST) on Polar and the Spectrometer for INTEGRAL (SPI). We seek causal correlations between the observed GCR modulations and structures in the solar wind plasma and interplanetary magnetic field, as measured concurrently with ACE and/or Wind. Our analysis spans time-/size-scale variations ranging from classic Forbush decreases (Fds), to substructure embedded within Fds, to much smaller amplitude and shorter duration variations observed during comparatively benign interplanetary conditions. We compare and contrast the conditions leading to the range of different GCR responses to modulating structures in the IPM.

Effects of Cutoffs on Galactic Cosmic-Ray Interactions in Solar-System Matter

NASA Technical Reports Server (NTRS)

Kim, K. J.; Reedy, R. C.; Masarik, J.

2005-01-01

The energetic particles in the galactic cosmic rays (GCR) induce many interactions in a variety of solar-system matter. Cosmogenic nuclides are used to study the histories of meteorites and lunar samples. Gamma rays and neutrons are used to map the compositions of planetary surfaces, such as Mars, the Moon, and asteroids. In almost all of these cases, the spectra of incident GCR particles are fairly similar, with only some modulation by the Sun over an 11-year cycle. Strong magnetic fields can seriously affect the energy spectrum of GCR particles hitting the surface of objects inside the magnetic fields. The Earth s geomagnetic field is strong enough that only GCR particles with magnetic rigidities above approx. 17 GV (a proton energy of approx. 17 GeV) reach the atmosphere over certain regions near the equator. This effect of removing lower-energy GCR particles is called a cutoff. The jovian magnetic fields are so strong that the fluxes of GCR particles hitting the 4 large Galilean satellites are similarly affected. The cutoff at Europa is estimated to be similar to or a little higher than at the Earth s equator.

Monte Carlo Analysis of Pion Contribution to Absorbed Dose from Galactic Cosmic Rays

NASA Technical Reports Server (NTRS)

Aghara, S.K.; Battnig, S.R.; Norbury, J.W.; Singleterry, R.C.

2009-01-01

Accurate knowledge of the physics of interaction, particle production and transport is necessary to estimate the radiation damage to equipment used on spacecraft and the biological effects of space radiation. For long duration astronaut missions, both on the International Space Station and the planned manned missions to Moon and Mars, the shielding strategy must include a comprehensive knowledge of the secondary radiation environment. The distribution of absorbed dose and dose equivalent is a function of the type, energy and population of these secondary products. Galactic cosmic rays (GCR) comprised of protons and heavier nuclei have energies from a few MeV per nucleon to the ZeV region, with the spectra reaching flux maxima in the hundreds of MeV range. Therefore, the MeV - GeV region is most important for space radiation. Coincidentally, the pion production energy threshold is about 280 MeV. The question naturally arises as to how important these particles are with respect to space radiation problems. The space radiation transport code, HZETRN (High charge (Z) and Energy TRaNsport), currently used by NASA, performs neutron, proton and heavy ion transport explicitly, but it does not take into account the production and transport of mesons, photons and leptons. In this paper, we present results from the Monte Carlo code MCNPX (Monte Carlo N-Particle eXtended), showing the effect of leptons and mesons when they are produced and transported in a GCR environment.

Badhwar-O'Neill 2011 Galactic Cosmic Ray Model Update and Future Improvements

NASA Technical Reports Server (NTRS)

O'Neill, Pat M.; Kim, Myung-Hee Y.

2014-01-01

The Badhwar-O'Neill Galactic Cosmic Ray (GCR) Model based on actual GCR measurements is used by deep space mission planners for the certification of microelectronic systems and the analysis of radiation health risks to astronauts in space missions. The BO GCR Model provides GCR flux in deep space (outside the earth's magnetosphere) for any given time from 1645 to present. The energy spectrum from 50 MeV/n - 20 GeV/n is provided for ions from hydrogen to uranium. This work describes the most recent version of the BO GCR model (BO'11). BO'11 determined the GCR flux at a given time applying an emperical time delay function to past sunspot activity. We describe the GCR measurement data used in the BO'11 update - modern data from BESS, PAMELA, CAPRICE, and ACE emphasized more than the older balloon data used for the previous BO model (BO'10). We look at the GCR flux for the last 24 solar minima and show how much greater the flux was for the cycle 24 minimum in 2010. The BO'11 Model uses the traditional, steady-state Fokker-Planck differential equation to account for particle transport in the heliosphere due to diffusion, convection, and adiabatic deceleration. It assumes a radially symmetrical diffusion coefficient derived from magnetic disturbances caused by sunspots carried outward by a constant solar wind. A more complex differential equation is now being tested to account for particle transport in the heliosphere in the next generation BO model. This new model is time-dependent (no longer a steady state model). In the new model, the dynamics and anti-symmetrical features of the actual heliosphere are accounted for so emperical time delay functions will no longer be required. The new model will be capable of simulating the more subtle features of modulation - such as the Sun's polarity and modulation dependence on gradient and curvature drift. This improvement is expected to significantly improve the fidelity of the BO GCR model. Preliminary results of its performance will be presented.

Quasi-periodic changes in the 3D solar anisotropy of Galactic cosmic rays for 1965-2014

NASA Astrophysics Data System (ADS)

Modzelewska, R.; Alania, M. V.

2018-01-01

Aims: We study features of the 3D solar anisotropy of Galactic cosmic rays (GCR) for 1965-2014 (almost five solar cycles, cycles 20-24). We analyze the 27-day variations of the 2D GCR anisotropy in the ecliptic plane and the north-south anisotropy normal to the ecliptic plane. We study the dependence of the 27-day variation of the 3D GCR anisotropy on the solar cycle and solar magnetic cycle. We demonstrate that the 27-day variations of the GCR intensity and anisotropy can be used as an important tool to study solar wind, solar activity, and heliosphere. Methods: We used the components Ar, Aϕ and At of the 3D GCR anisotropy that were found based on hourly data of neutron monitors (NMs) and muon telescopes (MTs) using the harmonic analyses and spectrographic methods. We corrected the 2D diurnal ( 24-h) variation of the GCR intensity for the influence of the Earth magnetic field. We derived the north-south component of the GCR anisotropy based on the GG index, which is calculated as the difference in GCR intensities of the Nagoya multidirectional MTs. Results: We show that the behavior of the 27-day variation of the 3D anisotropy verifies a stable long-lived active heliolongitude on the Sun. This illustrates the usefulness of the 27-day variation of the GCR anisotropy as a unique proxy to study solar wind, solar activity, and heliosphere. We distinguish a tendency of the 22-yr changes in amplitude of the 27-day variation of the 2D anisotropy that is connected with the solar magnetic cycle. We demonstrate that the amplitudes of the 27-day variation of the north-south component of the anisotropy vary with the 11-yr solar cycle, but a dependence of the solar magnetic polarity can hardly be recognized. We show that the 27-day recurrences of the GG index and the At component are highly positively correlated, and both are highly correlated with the By component of the heliospheric magnetic field.

Galactic cosmic ray simulation at the NASA Space Radiation Laboratory

PubMed Central

Norbury, John W.; Schimmerling, Walter; Slaba, Tony C.; Azzam, Edouard I.; Badavi, Francis F.; Baiocco, Giorgio; Benton, Eric; Bindi, Veronica; Blakely, Eleanor A.; Blattnig, Steve R.; Boothman, David A.; Borak, Thomas B.; Britten, Richard A.; Curtis, Stan; Dingfelder, Michael; Durante, Marco; Dynan, William S.; Eisch, Amelia J.; Elgart, S. Robin; Goodhead, Dudley T.; Guida, Peter M.; Heilbronn, Lawrence H.; Hellweg, Christine E.; Huff, Janice L.; Kronenberg, Amy; La Tessa, Chiara; Lowenstein, Derek I.; Miller, Jack; Morita, Takashi; Narici, Livio; Nelson, Gregory A.; Norman, Ryan B.; Ottolenghi, Andrea; Patel, Zarana S.; Reitz, Guenther; Rusek, Adam; Schreurs, Ann-Sofie; Scott-Carnell, Lisa A.; Semones, Edward; Shay, Jerry W.; Shurshakov, Vyacheslav A.; Sihver, Lembit; Simonsen, Lisa C.; Story, Michael D.; Turker, Mitchell S.; Uchihori, Yukio; Williams, Jacqueline; Zeitlin, Cary J.

2017-01-01

Most accelerator-based space radiation experiments have been performed with single ion beams at fixed energies. However, the space radiation environment consists of a wide variety of ion species with a continuous range of energies. Due to recent developments in beam switching technology implemented at the NASA Space Radiation Laboratory (NSRL) at Brookhaven National Laboratory (BNL), it is now possible to rapidly switch ion species and energies, allowing for the possibility to more realistically simulate the actual radiation environment found in space. The present paper discusses a variety of issues related to implementation of galactic cosmic ray (GCR) simulation at NSRL, especially for experiments in radiobiology. Advantages and disadvantages of different approaches to developing a GCR simulator are presented. In addition, issues common to both GCR simulation and single beam experiments are compared to issues unique to GCR simulation studies. A set of conclusions is presented as well as a discussion of the technical implementation of GCR simulation. PMID:26948012

Galactic cosmic ray simulation at the NASA Space Radiation Laboratory.

PubMed

Norbury, John W; Schimmerling, Walter; Slaba, Tony C; Azzam, Edouard I; Badavi, Francis F; Baiocco, Giorgio; Benton, Eric; Bindi, Veronica; Blakely, Eleanor A; Blattnig, Steve R; Boothman, David A; Borak, Thomas B; Britten, Richard A; Curtis, Stan; Dingfelder, Michael; Durante, Marco; Dynan, William S; Eisch, Amelia J; Robin Elgart, S; Goodhead, Dudley T; Guida, Peter M; Heilbronn, Lawrence H; Hellweg, Christine E; Huff, Janice L; Kronenberg, Amy; La Tessa, Chiara; Lowenstein, Derek I; Miller, Jack; Morita, Takashi; Narici, Livio; Nelson, Gregory A; Norman, Ryan B; Ottolenghi, Andrea; Patel, Zarana S; Reitz, Guenther; Rusek, Adam; Schreurs, Ann-Sofie; Scott-Carnell, Lisa A; Semones, Edward; Shay, Jerry W; Shurshakov, Vyacheslav A; Sihver, Lembit; Simonsen, Lisa C; Story, Michael D; Turker, Mitchell S; Uchihori, Yukio; Williams, Jacqueline; Zeitlin, Cary J

2016-02-01

Most accelerator-based space radiation experiments have been performed with single ion beams at fixed energies. However, the space radiation environment consists of a wide variety of ion species with a continuous range of energies. Due to recent developments in beam switching technology implemented at the NASA Space Radiation Laboratory (NSRL) at Brookhaven National Laboratory (BNL), it is now possible to rapidly switch ion species and energies, allowing for the possibility to more realistically simulate the actual radiation environment found in space. The present paper discusses a variety of issues related to implementation of galactic cosmic ray (GCR) simulation at NSRL, especially for experiments in radiobiology. Advantages and disadvantages of different approaches to developing a GCR simulator are presented. In addition, issues common to both GCR simulation and single beam experiments are compared to issues unique to GCR simulation studies. A set of conclusions is presented as well as a discussion of the technical implementation of GCR simulation. Published by Elsevier Ltd.

Astrophysical Li-7 as a product of big bang nucleosynthesis and galactic cosmic-ray spallation

NASA Technical Reports Server (NTRS)

Olive, Keith A.; Schramm, David N.

1992-01-01

The astrophysical Li-7 abundance is considered to be largely primordial, while the Be and B abundances are thought to be due to galactic cosmic ray (GCR) spallation reactions on top of a much smaller big bang component. But GCR spallation should also produce Li-7. As a consistency check on the combination of big bang nucleosynthesis and GCR spallation, the Be and B data from a sample of hot population II stars is used to subtract from the measured Li-7 abundance an estimate of the amount generated by GCR spallation for each star in the sample, and then to add to this baseline an estimate of the metallicity-dependent augmentation of Li-7 due to spallation. The singly reduced primordial Li-7 abundance is still consistent with big bang nucleosynthesis, and a single GCR spallation model can fit the Be, B, and corrected Li-7 abundances for all the stars in the sample.

Heliospheric Transient Structures Associated with Short-Period Variations in the GCR Flux

NASA Astrophysics Data System (ADS)

Mulligan, T.; Blake, J.B.; Shaul, D.; Quenby, J.

Short-period variations in the integral GCR fluence ( > 100 MeV) often observed in neutron monitor data have also been seen by the High Sensitivity Telescope (HIST) aboard the Polar spacecraft. Although HIST was designed to measure radiation-belt electrons, it makes clean measurements of the integral GCR fluence when Polar is outside the radiation belts. These measurements show GCR variability on a variety of timescales including 0.1 mHz - 1 mHz. On August 20, 2006 a Forbush decrease observed at Polar was also seen at the INTEGRAL spacecraft. Data from Polar HIST and from INTEGRAL’s Ge detector saturation rate (GEDSAT), which also measures the GCR background with a threshold of ~200 MeV, show similar, coherent, short-period GCR variations at two very different locations within the Earth’s magnetosphere. Comparing these variations from Polar and INTEGRAL to solar wind magnetic field and plasma conditions at the L1 Libration point sunward of the Earth reveal this coherency occurs when Earth is in close proximity to and inside a flux rope interplanetary CME (ICME). Inversion of the ICME magnetic field results in a flux rope axial orientation nearly parallel to the radial direction. This orientation is consistent with a grazing passage of the ICME with the Earth. New measurements from STEREO will enable detailed 3-D analyses of such solar wind disturbances along spatial scales on the same order of typical SEP and GCR proton gyroradii, which are needed to help determine the mechanism behind this short-period variability.

MODULATION OF GALACTIC COSMIC RAYS OBSERVED AT L1 IN SOLAR CYCLE 23

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

Fludra, A., E-mail: Andrzej.Fludra@stfc.ac.uk

2015-01-20

We analyze a unique 15 yr record of galactic cosmic-ray (GCR) measurements made by the SOHO Coronal Diagnostic Spectrometer NIS detectors, recording integrated GCR numbers with energies above 1.0 GeV between 1996 July and 2011 June. We are able to closely reproduce the main features of the SOHO/CDS GCR record using the modulation potential calculated from neutron monitor data by Usoskin et al. The GCR numbers show a clear solar cycle modulation: they decrease by 50% from the 1997 minimum to the 2000 maximum of the solar cycle, then return to the 1997 level in 2007 and continue to rise, in 2009 Decembermore » reaching a level 25% higher than in 1997. This 25% increase is in contrast with the behavior of Ulysses/KET GCR protons extrapolated to 1 AU in the ecliptic plane, showing the same level in 2008-2009 as in 1997. The GCR numbers are inversely correlated with the tilt angle of the heliospheric current sheet. In particular, the continued increase of SOHO/CDS GCRs from 2007 until 2009 is correlated with the decrease of the minimum tilt angle from 30° in mid-2008 to 5° in late 2009. The GCR level then drops sharply from 2010 January, again consistent with a rapid increase of the tilt angle to over 35°. This shows that the extended 2008 solar minimum was different from the 1997 minimum in terms of the structure of the heliospheric current sheet.« less

Development of diagnostic prediction tools for bacteraemia caused by third-generation cephalosporin-resistant enterobacteria in suspected bacterial infections: a nested case-control study.

PubMed

Rottier, W C; van Werkhoven, C H; Bamberg, Y R P; Dorigo-Zetsma, J W; van de Garde, E M; van Hees, B C; Kluytmans, J A J W; Kuck, E M; van der Linden, P D; Prins, J M; Thijsen, S F T; Verbon, A; Vlaminckx, B J M; Ammerlaan, H S M; Bonten, M J M

2018-03-23

Current guidelines for the empirical antibiotic treatment predict the presence of third-generation cephalosporin-resistant enterobacterial bacteraemia (3GCR-E-Bac) in case of infection only poorly, thereby increasing unnecessary carbapenem use. We aimed to develop diagnostic scoring systems which can better predict the presence of 3GCR-E-Bac. A retrospective nested case-control study was performed that included patients ≥18 years of age from eight Dutch hospitals in whom blood cultures were obtained and intravenous antibiotics were initiated. Each patient with 3GCR-E-Bac was matched to four control infection episodes within the same hospital, based on blood-culture date and onset location (community or hospital). Starting from 32 commonly described clinical risk factors at infection onset, selection strategies were used to derive scoring systems for the probability of community- and hospital-onset 3GCR-E-Bac. 3GCR-E-Bac occurred in 90 of 22 506 (0.4%) community-onset infections and in 82 of 8110 (1.0%) hospital-onset infections, and these cases were matched to 360 community-onset and 328 hospital-onset control episodes. The derived community-onset and hospital-onset scoring systems consisted of six and nine predictors, respectively. With selected score cut-offs, the models identified 3GCR-E-Bac with sensitivity equal to existing guidelines (community-onset: 54.3%; hospital-onset: 81.5%). However, they reduced the proportion of patients classified as at risk for 3GCR-E-Bac (i.e. eligible for empirical carbapenem therapy) with 40% (95%CI 21-56%) and 49% (95%CI 39-58%) in, respectively, community-onset and hospital-onset infections. These prediction scores for 3GCR-E-Bac, specifically geared towards the initiation of empirical antibiotic treatment, may improve the balance between inappropriate antibiotics and carbapenem overuse. Copyright © 2018 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Evaluations of Risks from the Lunar and Mars Radiation Environments

NASA Technical Reports Server (NTRS)

Kim, Myung-Hee; Hayat, Matthew J.; Feiveson, Alan H.; Cucinotta, Francis A.

2008-01-01

Protecting astronauts from the space radiation environments requires accurate projections of radiation in future space missions. Characterization of the ionizing radiation environment is challenging because the interplanetary plasma and radiation fields are modulated by solar disturbances and the radiation doses received by astronauts in interplanetary space are likewise influenced. The galactic cosmic radiation (GCR) flux for the next solar cycle was estimated as a function of interplanetary deceleration potential, which has been derived from GCR flux and Climax neutron monitor rate measurements over the last 4 decades. For the chaotic nature of solar particle event (SPE) occurrence, the mean frequency of SPE at any given proton fluence threshold during a defined mission duration was obtained from a Poisson process model using proton fluence measurements of SPEs during the past 5 solar cycles (19-23). Analytic energy spectra of 34 historically large SPEs were constructed over broad energy ranges extending to GeV. Using an integrated space radiation model (which includes the transport codes HZETRN [1] and BRYNTRN [2], and the quantum nuclear interaction model QMSFRG[3]), the propagation and interaction properties of the energetic nucleons through various media were predicted. Risk assessment from GCR and SPE was evaluated at the specific organs inside a typical spacecraft using CAM [4] model. The representative risk level at each event size and their standard deviation were obtained from the analysis of 34 SPEs. Risks from different event sizes and their frequency of occurrences in a specified mission period were evaluated for the concern of acute health effects especially during extra-vehicular activities (EVA). The results will be useful for the development of an integrated strategy of optimizing radiation protection on the lunar and Mars missions. Keywords: Space Radiation Environments; Galactic Cosmic Radiation; Solar Particle Event; Radiation Risk; Risk Analysis; Radiation Protection.

Superbugs in the supermarket? Assessing the rate of contamination with third-generation cephalosporin-resistant gram-negative bacteria in fresh Australian pork and chicken.

PubMed

McLellan, Jade E; Pitcher, Joshua I; Ballard, Susan A; Grabsch, Elizabeth A; Bell, Jan M; Barton, Mary; Grayson, M Lindsay

2018-01-01

Antibiotic misuse in food-producing animals is potentially associated with human acquisition of multidrug-resistant (MDR; resistance to ≥ 3 drug classes) bacteria via the food chain. We aimed to determine if MDR Gram-negative (GNB) organisms are present in fresh Australian chicken and pork products. We sampled raw, chicken drumsticks (CD) and pork ribs (PR) from 30 local supermarkets/butchers across Melbourne on two occasions. Specimens were sub-cultured onto selective media for third-generation cephalosporin-resistant (3GCR) GNBs, with species identification and antibiotic susceptibility determined for all unique colonies. Isolates were assessed by PCR for SHV, TEM, CTX-M, AmpC and carbapenemase genes (encoding IMP, VIM, KPC, OXA-48, NDM). From 120 specimens (60 CD, 60 PR), 112 (93%) grew a 3GCR-GNB ( n  = 164 isolates; 86 CD, 78 PR); common species were Acinetobacter baumannii (37%), Pseudomonas aeruginosa (13%) and Serratia fonticola (12%), but only one E. coli isolate. Fifty-nine (36%) had evidence of 3GCR alone, 93/163 (57%) displayed 3GCR plus resistance to one additional antibiotic class, and 9/163 (6%) were 3GCR plus resistance to two additional classes. Of 158 DNA specimens, all were negative for ESBL/carbapenemase genes, except 23 (15%) which were positive for AmpC, with 22/23 considered to be inherently chromosomal, but the sole E. coli isolate contained a plasmid-mediated CMY-2 AmpC. We found low rates of MDR-GNBs in Australian chicken and pork meat, but potential 3GCR-GNBs are common (93% specimens). Testing programs that only assess for E. coli are likely to severely underestimate the diversity of 3GCR organisms in fresh meat.

Calculation of The Ti Activity In 44 Chondrites Which Fell In The Last Two Centuries and Comparison With Measurements

NASA Astrophysics Data System (ADS)

Bonino, G.; Cane, D.; Cini Castagnoli, G.; Taricco, C.; Bhandari, N.

The cosmogenic radioisotopes in meteorites, produced by nuclear interactions of the galactic cosmic rays (GCR) with the meteoroids in the interplanetary space are good proxies of both the GCR flux and the solar activity. Different cosmogenic radionu- clides with different half-lives give information over different time scales. Recently we have inferred the GCR annual mean spectra for the last 300 years [1]. The most prominent result concerns the cosmic ray flux during prolonged solar quiet periods. We deduced that during the Maunder minimum of solar acivity (1700), the Dal- ton minimum (1800) and the Modern minimum (1900) the GCR flux was much higher (2 times) respect to the flux observed in the last decades. Utilizing these GCR spectra we have calculated the 44 Ti (T1/2 = 59.2 y) activity in meteorites taking into account its exitation function for production from the main target element Fe, Ni and Ti [2]. Furthermore, in the last years we have measured the very low activity of the cosmogenic 44Ti in different fell chondrites and now our data cover the interval 1810 to present. The calculated 44Ti profile is in close agreement with the observed mea- surements. This result demonstrates that our inference of the GCR flux in the past 300 years is reliable. The cosmogenic 44Ti in meteorites is a unique tool, free from ter- restrial influences, for validation of both the GCR flux and the heliospheric behaviour over century time scale. [1] G. Bonino, G. Cini Castagnoli, D. Cane, C. Taricco and N. Bhandari, Proc. XXVII Intern. Cosmic Ray Conf. (Hamburg, 2001) 3769-3772. [2] R. Michel and S. Neumann (1998) Proc. Indian Acad. Sci. Earth Planet. Sci. , 107, 441-457.

Uganda experience-Using cost assessment of an established registry to project resources required to expand cancer registration.

PubMed

Wabinga, Henry; Subramanian, Sujha; Nambooze, Sarah; Amulen, Phoebe Mary; Edwards, Patrick; Joseph, Rachael; Ogwang, Martin; Okongo, Francis; Parkin, D Maxwell; Tangka, Florence

2016-12-01

The objectives of this study are (1) to estimate the cost of operating the Kampala Cancer Registry (KCR) and (2) to use cost data from the KCR to project the resource needs and cost of expanding and sustaining cancer registration in Uganda, focusing on the recently established Gulu Cancer Registry (GCR) in rural Northern Uganda. We used Centers for Disease Control and Prevention's (CDC's) International Registry Costing Tool (IntRegCosting Tool) to estimate the KCR's activity-based cost for 2014. We grouped the registry activities into fixed cost, variable core cost, and variable other cost activities. After a comparison KCR and GCR characteristics, we used the cost of the KCR to project the likely ongoing costs for the new GCR. The KCR incurred 42% of its expenditures in fixed cost activities, 40% for variable core cost activities, and the remaining 18% for variable other cost activities. The total cost per case registered was 28,201 Ugandan shillings (approximately US $10 in 2014) to collect and report cases using a combination of passive and active cancer data collection approaches. The GCR performs only active data collection, and covers a much larger area, but serves a smaller population compared to the KCR. After identifying many differences between KCR and GCR that could potentially affect the cost of registration, our best estimate is that the GCR, though newer and in a rural area, should require fewer resources than the KCR to sustain operations as a stand-alone entity. The optimal structure of the GCR needs to be determined in the future. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

Guo, X.; Florinski, V.

We present a new model that couples galactic cosmic-ray (GCR) propagation with magnetic turbulence transport and the MHD background evolution in the heliosphere. The model is applied to the problem of the formation of corotating interaction regions (CIRs) during the last solar minimum from the period between 2007 and 2009. The numerical model simultaneously calculates the large-scale supersonic solar wind properties and its small-scale turbulent content from 0.3 au to the termination shock. Cosmic rays are then transported through the background, and thus computed, with diffusion coefficients derived from the solar wind turbulent properties, using a stochastic Parker approach. Ourmore » results demonstrate that GCR variations depend on the ratio of diffusion coefficients in the fast and slow solar winds. Stream interfaces inside the CIRs always lead to depressions of the GCR intensity. On the other hand, heliospheric current sheet (HCS) crossings do not appreciably affect GCR intensities in the model, which is consistent with the two observations under quiet solar wind conditions. Therefore, variations in diffusion coefficients associated with CIR stream interfaces are more important for GCR propagation than the drift effects of the HCS during a negative solar minimum.« less

Galactic Cosmic Ray Intensity in the Upcoming Minimum of the Solar Activity Cycle

NASA Astrophysics Data System (ADS)

Krainev, M. B.; Bazilevskaya, G. A.; Kalinin, M. S.; Svirzhevskaya, A. K.; Svirzhevskii, N. S.

2018-03-01

During the prolonged and deep minimum of solar activity between cycles 23 and 24, an unusual behavior of the heliospheric characteristics and increased intensity of galactic cosmic rays (GCRs) near the Earth's orbit were observed. The maximum of the current solar cycle 24 is lower than the previous one, and the decline in solar and, therefore, heliospheric activity is expected to continue in the next cycle. In these conditions, it is important for an understanding of the process of GCR modulation in the heliosphere, as well as for applied purposes (evaluation of the radiation safety of planned space flights, etc.), to estimate quantitatively the possible GCR characteristics near the Earth in the upcoming solar minimum ( 2019-2020). Our estimation is based on the prediction of the heliospheric characteristics that are important for cosmic ray modulation, as well as on numeric calculations of GCR intensity. Additionally, we consider the distribution of the intensity and other GCR characteristics in the heliosphere and discuss the intercycle variations in the GCR characteristics that are integral for the whole heliosphere (total energy, mean energy, and charge).

Response of the Earth’s lower ionosphere to the Ground Level Enhancement event of December 13, 2006

NASA Astrophysics Data System (ADS)

Žigman, Vida; Kudela, Karel; Grubor, Davorka

2014-03-01

In this study we analyze the Ground Level Enhancement Event No 70 observed on December 13, 2006, by correlating the observations from two research topics: Cosmic rays and Very Low Frequency (VLF < 30 kHz) wave propagation, as two ground based techniques for the detection of solar proton events, and their impact on the lower ionosphere. The observations have been endorsed from recordings of worldwide network ground based Neutron Monitors as well as by satellite data from the satellites GOES 12 (www.swpc.noaa.gov) and Pamela (www.pamela.roma2infn.it). We have evaluated the ionization rate for protons in the altitude range relevant to VLF propagation, and for galactic cosmic ray (GCR) background, finding that at energies up to ˜2 GeV the ionization rate of solar protons exceeded the GCR ionization by 1.5 orders of magnitude. We have applied the Long Wave Propagation Capability (LWPC) code to evaluate the enhancement of the electron density from VLF signal perturbation and have inferred corresponding electron densities from the evaluated ionization rates and effective recombination coefficients from literature, to find the two independent sets in good agreement.

Observations of the Li, Be, and B Isotopes and Constraints on Cosmic-ray Propagation

NASA Technical Reports Server (NTRS)

deNolfo, G. A.; Moskalenko, I. V.; Binns, W. R.; Christian, E. R.; Cummings, A. C.; Davis, A. J.; George, J. S.; Hink, P. L.; Israel, M. H.; Leske, R. A.;

Badhwar-O'Neill 2011 Galactic Cosmic Ray Model Update and Future Improvements

NASA Technical Reports Server (NTRS)

O'Neill, Pat M.; Kim, Myung-Hee Y.

2014-01-01

The Badhwar-O'Neill Galactic Cosmic Ray (GCR) Model based on actual GR measurements is used by deep space mission planners for the certification of micro-electronic systems and the analysis of radiation health risks to astronauts in space missions. The BO GCR Model provides GCR flux in deep space (outside the earth's magnetosphere) for any given time from 1645 to present. The energy spectrum from 50 MeV/n-20 GeV/n is provided for ions from hydrogen to uranium. This work describes the most recent version of the BO GCR model (BO'11). BO'11 determines the GCR flux at a given time applying an empirical time delay function to past sunspot activity. We describe the GCR measurement data used in the BO'11 update - modern data from BESS, PAMELA, CAPRICE, and ACE emphasized for than the older balloon data used for the previous BO model (BO'10). We look at the GCR flux for the last 24 solar minima and show how much greater the flux was for the cycle 24 minimum in 2010. The BO'11 Model uses the traditional, steady-state Fokker-Planck differential equation to account for particle transport in the heliosphere due to diffusion, convection, and adiabatic deceleration. It assumes a radially symmetrical diffusion coefficient derived from magnetic disturbances caused by sunspots carried onward by a constant solar wind. A more complex differential equation is now being tested to account for particle transport in the heliosphere in the next generation BO model. This new model is time-dependent (no longer a steady state model). In the new model, the dynamics and anti-symmetrical features of the actual heliosphere are accounted for so empirical time delay functions will no longer be required. The new model will be capable of simulating the more subtle features of modulation - such as the Sun's polarity and modulation dependence on the gradient and curvature drift. This improvement is expected to significantly improve the fidelity of the BO GCR model. Preliminary results of its performance will be presented.

Directly spheroidizing during hot deformation in GCr15 steels

NASA Astrophysics Data System (ADS)

Zhu, Guo-hui; Zheng, Gang

2008-03-01

The spheroidizing heat treatment is normally required prior to the cold forming in GCr15 steel in order to improve its machinability. In the conventional spheroidizing process, very long annealing time, generally more than 10 h, is needed to assure proper spheroidizing. It results in low productivity, high cost, and especially high energy consumption. Therefore, the possibility of directly spheroidizing during hot deformation in GCr15 steel is preliminarily explored. The effect of hot deformation parameters on the final microstructure and hardness is investigated systematically in order to develop a directly spheroidizing technology. Experimental results illustrate that low deformation temperature and slow cooling rate is the favorite in directly softening and/or spheroidizing during hot deformation, which allows the properties of asrolled GCr15 to be applicable for post-machining without requirement of prior annealing.

Monitoring Short-term Cosmic-ray Spectral Variations Using Neutron Monitor Time-delay Measurements

NASA Astrophysics Data System (ADS)

Ruffolo, D.; Sáiz, A.; Mangeard, P.-S.; Kamyan, N.; Muangha, P.; Nutaro, T.; Sumran, S.; Chaiwattana, C.; Gasiprong, N.; Channok, C.; Wuttiya, C.; Rujiwarodom, M.; Tooprakai, P.; Asavapibhop, B.; Bieber, J. W.; Clem, J.; Evenson, P.; Munakata, K.

2016-01-01

Neutron monitors (NMs) are ground-based detectors of cosmic-ray showers that are widely used for high-precision monitoring of changes in the Galactic cosmic-ray (GCR) flux due to solar storms and solar wind variations. In the present work, we show that a single neutron monitor station can also monitor short-term changes in the GCR spectrum, avoiding the systematic uncertainties in comparing data from different stations, by means of NM time-delay histograms. Using data for 2007-2014 from the Princess Sirindhorn Neutron Monitor, a station at Doi Inthanon, Thailand, with the world’s highest vertical geomagnetic cutoff rigidity of 16.8 GV, we have developed an analysis of time-delay histograms that removes the chance coincidences that can dominate conventional measures of multiplicity. We infer the “leader fraction” L of neutron counts that do not follow a previous neutron count in the same counter from the same atmospheric secondary, which is inversely related to the actual multiplicity and increases for increasing GCR spectral index. After correction for atmospheric pressure and water vapor, we find that L indicates substantial short-term GCR spectral hardening during some but not all Forbush decreases in GCR flux due to solar storms. Such spectral data from Doi Inthanon provide information about cosmic-ray energies beyond the Earth’s maximum geomagnetic cutoff, extending the reach of the worldwide NM network and opening a new avenue in the study of short-term GCR decreases.

MONITORING SHORT-TERM COSMIC-RAY SPECTRAL VARIATIONS USING NEUTRON MONITOR TIME-DELAY MEASUREMENTS

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

Ruffolo, D.; Sáiz, A.; Mangeard, P.-S.

Neutron monitors (NMs) are ground-based detectors of cosmic-ray showers that are widely used for high-precision monitoring of changes in the Galactic cosmic-ray (GCR) flux due to solar storms and solar wind variations. In the present work, we show that a single neutron monitor station can also monitor short-term changes in the GCR spectrum, avoiding the systematic uncertainties in comparing data from different stations, by means of NM time-delay histograms. Using data for 2007–2014 from the Princess Sirindhorn Neutron Monitor, a station at Doi Inthanon, Thailand, with the world’s highest vertical geomagnetic cutoff rigidity of 16.8 GV, we have developed anmore » analysis of time-delay histograms that removes the chance coincidences that can dominate conventional measures of multiplicity. We infer the “leader fraction” L of neutron counts that do not follow a previous neutron count in the same counter from the same atmospheric secondary, which is inversely related to the actual multiplicity and increases for increasing GCR spectral index. After correction for atmospheric pressure and water vapor, we find that L indicates substantial short-term GCR spectral hardening during some but not all Forbush decreases in GCR flux due to solar storms. Such spectral data from Doi Inthanon provide information about cosmic-ray energies beyond the Earth’s maximum geomagnetic cutoff, extending the reach of the worldwide NM network and opening a new avenue in the study of short-term GCR decreases.« less

Local and nonlocal geometry of interplanetary coronal mass ejections: Galactic cosmic ray (GCR) short-period variations and magnetic field modeling

NASA Astrophysics Data System (ADS)

Quenby, J. J.; Mulligan, T.; Blake, J. B.; Mazur, J. E.; Shaul, D.

2008-10-01

Energetic galactic cosmic ray (GCR) particles, arriving within the solar system, are modulated by the overall interplanetary field carried in the solar wind. Localized disturbances related to solar activity cause further reduction in intensity, the largest being Forbush decreases in which fluxes can fall ˜20% over a few days. Understanding Forbush decreases leads to a better understanding of the magnetic field structure related to shock waves and fast streams originating at the Sun since the propagation characteristics of the GCR probe much larger regions of space than do individual spacecraft instruments. We examined the temporal history of the integral GCR fluence (≥100 MeV) measured by the high-sensitivity telescope (HIST) aboard the Polar spacecraft, along with the solar wind magnetic field and plasma data from the ACE spacecraft during a 40-day period encompassing the 25 September 1998 Forbush decrease. We also examined the Forbush and (energetic storm particles) ESP event on 28 October 2003. It is the use of HIST in a high-counting-rate integral mode that allows previously poorly seen, short-scale depressions in the GCR fluxes to be observed, adding crucial information on the origin of GCR modulation. Variability on time scales within the frequency range 0.001-1.0 mHz is detected. This paper concentrates on investigating four simple models for explaining short-term reductions in the GCR intensity of both small and large amplitude. Specifically, these models are a local increase in magnetic scattering power, the passage of a shock discontinuity, and the passage of a tangential discontinuity or magnetic rope in the solar wind plasma. Analysis of the short-scale GCR depressions during a test period in September through October 1998 shows that they are not correlated with changes in magnetic scattering power or fluctuations in solar wind speed or plasma density. However, magnetic field and plasma data during the test period of Forbush decrease strongly suggest the presence of an interplanetary coronal mass ejection (ICME). Use of a non-force-free magnetic rope model in conjunction with the energetic particle data allows modeling of the geometry of the ICME in terms of a magnetic cloud topology. It is only this cloud configuration that allows a satisfactory explanation of the magnitude of the Forbush event of 25 September 1998. Calculations made during the test period point to short-scale GCR depressions being caused by either small-scale magnetic flux rope structures or possibly tangential discontinuities in the solar wind.

Cloud cover anomalies at middle latitudes: Links to troposphere dynamics and solar variability

NASA Astrophysics Data System (ADS)

Veretenenko, S.; Ogurtsov, M.

2016-11-01

In this work we study links between low cloud anomalies (LCA) at middle latitudes of the Northern and Southern hemispheres and galactic cosmic ray (GCR) variations used as a proxy of solar variability on the decadal time scale. It was shown that these links are not direct, but realized through GCR/solar activity phenomena influence on the development of extratropical baric systems (cyclones and troughs) which form cloud field. The violation of a positive correlation between LCA and GCR intensity which was observed in the 1980s-1990s occurred simultaneously in the Northern and Southern hemispheres in the early 2000s and coincided with the sign reversal of GCR effects on troposphere circulation. It was suggested that a possible reason for the correlation reversal between cyclonic activity at middle latitudes and GCR fluxes is the change of the stratospheric polar vortex intensity which influences significantly the troposphere-stratosphere coupling. The evidences for a noticeable weakening of the polar vortices in the Arctic and Antarctic stratosphere in the early 2000s are provided. The results obtained suggest an important role of the polar vortex evolution as a reason for a temporal variability of solar activity effects on the lower atmosphere.

Platinum isotopes in iron meteorites: Galactic cosmic ray effects and nucleosynthetic homogeneity in the p-process isotope 190Pt and the other platinum isotopes

NASA Astrophysics Data System (ADS)

Hunt, Alison C.; Ek, Mattias; Schönbächler, Maria

2017-11-01

Platinum isotopes are sensitive to the effects of galactic cosmic rays (GCR), which can alter isotope ratios and mask nucleosynthetic isotope variations. Platinum also features one p-process isotope, 190Pt, which is very low abundance and therefore challenging to analyse. Platinum-190 is relevant for early solar-system chronology because of its decay to 186Os. Here, we present new Pt isotope data for five iron meteorite groups (IAB, IIAB, IID, IIIAB and IVA), including high-precision measurements of 190Pt for the IAB, IIAB and IIIAB irons, determined by multi-collector ICPMS. New data are in good agreement with previous studies and display correlations between different Pt isotopes. The slopes of these correlations are well-reproduced by the available GCR models. We report Pt isotope ratios for the IID meteorite Carbo that are consistently higher than the predicted effects from the GCR model. This suggests that the model predictions do not fully account for all the GCR effects on Pt isotopes, but also that the pre-atmospheric radii and exposure times calculated for Carbo may be incorrect. Despite this, the good agreement of relative effects in Pt isotopes with the predicted GCR trends confirms that Pt isotopes are a useful in-situ neutron dosimeter. Once GCR effects are accounted for, our new dataset reveals s- and r-process homogeneity between the iron meteorite groups studied here and the Earth. New 190Pt data for the IAB, IIAB and IIIAB iron meteorites indicate the absence of GCR effects and homogeneity in the p-process isotope between these groups and the Earth. This corresponds well with results from other heavy p-process isotopes and suggests their homogenous distribution in the inner solar system, although it does not exclude that potential p-process isotope variations are too diluted to be currently detectable.

GCR Simulator Development Status at the NASA Space Radiation Laboratory

NASA Technical Reports Server (NTRS)

Slaba, T. C.; Norbury, J. W.; Blattnig, S. R.

2015-01-01

There are large uncertainties connected to the biological response for exposure to galactic cosmic rays (GCR) on long duration deep space missions. In order to reduce the uncertainties and gain understanding about the basic mechanisms through which space radiation initiates cancer and other endpoints, radiobiology experiments are performed with mono-energetic ions beams. Some of the accelerator facilities supporting such experiments have matured to a point where simulating the broad range of particles and energies characteristic of the GCR environment in a single experiment is feasible from a technology, usage, and cost perspective. In this work, several aspects of simulating the GCR environment at the NASA Space Radiation Laboratory (NSRL) are discussed. First, comparisons are made between direct simulation of the external, free space GCR field, and simulation of the induced tissue field behind shielding. It is found that upper energy constraints at NSRL limit the ability to simulate the external, free space field directly (i.e. shielding placed in the beam line in front of a biological target and exposed to a free space spectrum). Second, a reference environment for the GCR simulator and suitable for deep space missions is identified and described in terms of fluence and integrated dosimetric quantities. Analysis results are given to justify the use of a single reference field over a range of shielding conditions and solar activities. Third, an approach for simulating the reference field at NSRL is presented. The approach directly considers the hydrogen and helium energy spectra, and the heavier ions are collectively represented by considering the linear energy transfer (LET) spectrum. While many more aspects of the experimental setup need to be considered before final implementation of the GCR simulator, this preliminary study provides useful information that should aid the final design. Possible drawbacks of the proposed methodology are discussed and weighed against alternative simulation strategies.

Identification of Licopyranocoumarin and Glycyrurol from Herbal Medicines as Neuroprotective Compounds for Parkinson's Disease

PubMed Central

Fujimaki, Takahiro; Saiki, Shinji; Tashiro, Etsu; Yamada, Daisuke; Kitagawa, Mitsuhiro; Hattori, Nobutaka; Imoto, Masaya

2014-01-01

In the course of screening for the anti-Parkinsonian drugs from a library of traditional herbal medicines, we found that the extracts of choi-joki-to and daio-kanzo-to protected cells from MPP+-induced cell death. Because choi-joki-to and daio-kanzo-to commonly contain the genus Glycyrrhiza, we isolated licopyranocoumarin (LPC) and glycyrurol (GCR) as potent neuroprotective principals from Glycyrrhiza. LPC and GCR markedly blocked MPP+-induced neuronal PC12D cell death and disappearance of mitochondrial membrane potential, which were mediated by JNK. LPC and GCR inhibited MPP+-induced JNK activation through the suppression of reactive oxygen species (ROS) generation, thereby inhibiting MPP+-induced neuronal PC12D cell death. These results indicated that LPC and GCR derived from choi-joki-to and daio-kanzo-to would be promising drug leads for PD treatment in the future. PMID:24960051

Preface: Solar energetic particles, solar modulation and space radiation: New opportunities in the AMS-02 Era

NASA Astrophysics Data System (ADS)

Bindi, Veronica

2017-08-01

Solar Energetic Particle (SEP) acceleration at high energies and their propagation through the heliosphere and into the magnetosphere are not well understood and are still a matter of debate. Our understanding of solar modulation and transport of different species of galactic cosmic rays (GCR) inside the heliosphere has been significantly improved; however, a lot of work still needs to be done. GCR and SEPs pose a significant radiation risk for people and technology in space, and thus it is becoming increasingly important to understand the space radiation environment. AMS-02 will provide brand new information with unprecedented statistics about GCR and SEPs. Both GCR and heliophysics experiments will contribute to the increased understanding of acceleration physics, and transport of particles in space with improved models. This will inevitably lead to better predictions of space weather and safer operations in space.

The Flux of Galactic Cosmic Rays over the last 200,000 Years calculated from Beryllium-10 Records in deep Sea Sediments

NASA Astrophysics Data System (ADS)

Christl, M.; Strobl, C.; Mangini, A.; Kubik, P.

2003-04-01

The production of cosmogenic radionuclides like 10Be and 14C in the Earth's atmosphere is directly related to the flux of galactic cosmic rays (GCR) reaching the Earth's orbit. Measuring the depositional flux of 10Be, as deposited in marine sediments, therefore provides a good tool to reconstruct the GCR-flux and to study the presumed GCR-climate connection on millennial time scales. However, the deposition of 10Be into deep sea sediments also can be influenced strongly by climatically induced oceanic transport processes like sediment redistribution of adsorbed 10Be and lateral transport of dissolved 10Be. Consequently, the bulk deposition of 10Be can not be used to reconstruct the global GCR-flux. The global 10Be-production is separated from the transport signal by applying a correction procedure. While sediment redistribution is corrected by using the well established 230Thex-normalization methoda, the transport of dissolved 10Be is quantified by using a simple box model that is able to describe water mass transport and sedimentation of 10Be in the ocean. The transport-corrected 10Be-profiles represent global production changes. They can be used to calculate the flux of GCRs during the last 200,000 years (based on simulations presented by Masarik and Beerb). The comparison of the GCR-flux with climate records from stalagmites from lowc and midd latitudes shows a correlation between the growth periodes of stalagmites and times of low GCR-flux. The 10Be-based record of the GCR-flux also can be used in paleoclimate models to study the presumed GCR-climate connection on millennial timescales. begin{small} aFrank et al., in Use of Proxies in Paleoceanography: Examples from the South Atlantic (eds. Fischer, G. &Wefer, G.), 409-426 (Springer-Verlag, New York, 1999). bMasarik and Beer, Simulation of particle fluxes and cosmogenic nuclide production in the Earth's atmosphere. JGR-Atmospheres 104, 12099-12111 (1999). cNeff et al., Strong coherence between solar variability and the monsoon in Oman between 9 and 6 kyr ago. Nature 411, 290-293 (2001). dSpoetl et al., Start of the last interglacial period at 135 ka: Evidence from a high Alpine speleothem. Geology 30, 815-818 (2002).

Development of a GCR Event-based Risk Model

NASA Technical Reports Server (NTRS)

Cucinotta, Francis A.; Ponomarev, Artem L.; Plante, Ianik; Carra, Claudio; Kim, Myung-Hee

2009-01-01

A goal at NASA is to develop event-based systems biology models of space radiation risks that will replace the current dose-based empirical models. Complex and varied biochemical signaling processes transmit the initial DNA and oxidative damage from space radiation into cellular and tissue responses. Mis-repaired damage or aberrant signals can lead to genomic instability, persistent oxidative stress or inflammation, which are causative of cancer and CNS risks. Protective signaling through adaptive responses or cell repopulation is also possible. We are developing a computational simulation approach to galactic cosmic ray (GCR) effects that is based on biological events rather than average quantities such as dose, fluence, or dose equivalent. The goal of the GCR Event-based Risk Model (GERMcode) is to provide a simulation tool to describe and integrate physical and biological events into stochastic models of space radiation risks. We used the quantum multiple scattering model of heavy ion fragmentation (QMSFRG) and well known energy loss processes to develop a stochastic Monte-Carlo based model of GCR transport in spacecraft shielding and tissue. We validated the accuracy of the model by comparing to physical data from the NASA Space Radiation Laboratory (NSRL). Our simulation approach allows us to time-tag each GCR proton or heavy ion interaction in tissue including correlated secondary ions often of high multiplicity. Conventional space radiation risk assessment employs average quantities, and assumes linearity and additivity of responses over the complete range of GCR charge and energies. To investigate possible deviations from these assumptions, we studied several biological response pathway models of varying induction and relaxation times including the ATM, TGF -Smad, and WNT signaling pathways. We then considered small volumes of interacting cells and the time-dependent biophysical events that the GCR would produce within these tissue volumes to estimate how GCR event rates mapped to biological signaling induction and relaxation times. We considered several hypotheses related to signaling and cancer risk, and then performed simulations for conditions where aberrant or adaptive signaling would occur on long-duration space mission. Our results do not support the conventional assumptions of dose, linearity and additivity. A discussion on how event-based systems biology models, which focus on biological signaling as the mechanism to propagate damage or adaptation, can be further developed for cancer and CNS space radiation risk projections is given.

Pulsed Magnetic Field Driven Gas Core Reactors for Space Power & Propulsion Applications

NASA Technical Reports Server (NTRS)

Anghaie, Samim; Smith, Blair; Knight, Travis; Butler, Carey

2003-01-01

The present results indicated that: 1. A pulsed magnetic driven fission power concept, PMD-GCR is developed for closed (NER) and semi-open (NTR) operations. 2. In power mode, power is generated at alpha less than 1 for power levels of hundreds of KW or higher 3. IN semi open NTR mode, PMD-GCR generates thrust at I(sub sp) approx. 5,000 s and jet power approx. 5KW/Kg. 4. PMD-GCR is highly subcritical and is actively driven to critically. 5. Parallel path with fusion R&D needs in many areas including magnet and plasma.

Galactic Cosmic Ray Simulation at the NASA Space Radiation Laboratory

NASA Technical Reports Server (NTRS)

Norbury, John W.; Slaba, Tony C.; Rusek, Adam

2015-01-01

The external Galactic Cosmic Ray (GCR) spectrum is significantly modified when it passes through spacecraft shielding and astronauts. One approach for simulating the GCR space radiation environment at ground based accelerators would use the modified spectrum, rather than the external spectrum, in the accelerator beams impinging on biological targets. Two recent workshops have studied such GCR simulation. The first workshop was held at NASA Langley Research Center in October 2014. The second workshop was held at the NASA Space Radiation Investigators' workshop in Galveston, Texas in January 2015. The results of these workshops will be discussed in this paper.

Cosmic Ray Measurements Inside Mir With Sileye-2

NASA Astrophysics Data System (ADS)

Casolino, M.; Sileye-2 Team

smallIntensity of the coronal green line (small = 5303cm) is considered as an impor- tant parameter to characterize the changes of diffusion coefficient of galactic cosmic rays versus the solar activity. A contribution of the coronal green line intensity in GCR diffusion coefficient is taken into account using its real distribution on the whole disk of the Sun averaging for three days. An assumption is made that the observed changes of the intensity of the coronal green line on the Sun's surface is taken away to the in- terplanetary space with the average solar wind velocity, U = 400 km/s. Thus, to cover the modulation region of the size of the 100 AU there is necessary data of the coronal green line intensity of the one-year duration. Alternating the coefficient of proportion- ality between the intensity of coronal green line and the diffusion coefficient of GCR the appropriate correspondence between the observation of GCR intensity sensitive to neutron monitors and solution of the Parker's transport equation have been found. The best correspondence between the observation of GCR intensity and solution of the Parker's transport equation has been found when the role of the coronal green line intensity in diffusion coefficient of GCR is gradually diminished versus the distance from the Sun.

Generation of a Chinese Hamster Ovary Cell Line Producing Recombinant Human Glucocerebrosidase

PubMed Central

Novo, Juliana Branco; Morganti, Ligia; Moro, Ana Maria; Paes Leme, Adriana Franco; Serrano, Solange Maria de Toledo; Raw, Isaias; Ho, Paulo Lee

2012-01-01

Impaired activity of the lysosomal enzyme glucocerebrosidase (GCR) results in the inherited metabolic disorder known as Gaucher disease. Current treatment consists of enzyme replacement therapy by administration of exogenous GCR. Although effective, it is exceptionally expensive, and patients worldwide have a limited access to this medicine. In Brazil, the public healthcare system provides the drug free of charge for all Gaucher's patients, which reaches the order of $ 84 million per year. However, the production of GCR by public institutions in Brazil would reduce significantly the therapy costs. Here, we describe a robust protocol for the generation of a cell line producing recombinant human GCR. The protein was expressed in CHO-DXB11 (dhfr−) cells after stable transfection and gene amplification with methotrexate. As expected, glycosylated GCR was detected by immunoblotting assay both as cell-associated (~64 and 59 kDa) and secreted (63–69 kDa) form. Analysis of subclones allowed the selection of stable CHO cells producing a secreted functional enzyme, with a calculated productivity of 5.14 pg/cell/day for the highest producer. Although being laborious, traditional methods of screening high-producing recombinant cells may represent a valuable alternative to generate expensive biopharmaceuticals in countries with limited resources. PMID:23091360

Space Radiation Cancer Risks and Uncertainties for Mars Missions

NASA Technical Reports Server (NTRS)

Cucinotta, F. A.; Schimmerling, W.; Wilson, J. W.; Peterson, L. E.; Badhwar, G. D.; Saganti, P. B.; Dicello, J. F.

2001-01-01

Projecting cancer risks from exposure to space radiation is highly uncertain because of the absence of data for humans and because of the limited radiobiology data available for estimating late effects from the high-energy and charge (HZE) ions present in the galactic cosmic rays (GCR). Cancer risk projections involve many biological and physical factors, each of which has a differential range of uncertainty due to the lack of data and knowledge. We discuss an uncertainty assessment within the linear-additivity model using the approach of Monte Carlo sampling from subjective error distributions that represent the lack of knowledge in each factor to quantify the overall uncertainty in risk projections. Calculations are performed using the space radiation environment and transport codes for several Mars mission scenarios. This approach leads to estimates of the uncertainties in cancer risk projections of 400-600% for a Mars mission. The uncertainties in the quality factors are dominant. Using safety standards developed for low-Earth orbit, long-term space missions (>90 days) outside the Earth's magnetic field are currently unacceptable if the confidence levels in risk projections are considered. Because GCR exposures involve multiple particle or delta-ray tracks per cellular array, our results suggest that the shape of the dose response at low dose rates may be an additional uncertainty for estimating space radiation risks.

Evaluation of Spacecraft Shielding Effectiveness for Radiation Protection

NASA Technical Reports Server (NTRS)

Cucinotta, Francis A.; Wilson, John W.

1999-01-01

The potential for serious health risks from solar particle events (SPE) and galactic cosmic rays (GCR) is a critical issue in the NASA strategic plan for the Human Exploration and Development of Space (HEDS). The excess cost to protect against the GCR and SPE due to current uncertainties in radiation transmission properties and cancer biology could be exceedingly large based on the excess launch costs to shield against uncertainties. The development of advanced shielding concepts is an important risk mitigation area with the potential to significantly reduce risk below conventional mission designs. A key issue in spacecraft material selection is the understanding of nuclear reactions on the transmission properties of materials. High-energy nuclear particles undergo nuclear reactions in passing through materials and tissue altering their composition and producing new radiation types. Spacecraft and planetary habitat designers can utilize radiation transport codes to identify optimal materials for lowering exposures and to optimize spacecraft design to reduce astronaut exposures. To reach these objectives will require providing design engineers with accurate data bases and computationally efficient software for describing the transmission properties of space radiation in materials. Our program will reduce the uncertainty in the transmission properties of space radiation by improving the theoretical description of nuclear reactions and radiation transport, and provide accurate physical descriptions of the track structure of microscopic energy deposition.

A membrane glucocorticoid receptor mediates the rapid/non-genomic actions of glucocorticoids in mammalian skeletal muscle fibres

PubMed Central

Pérez, María Hernández-Alcalá; Cormack, Jonathan; Mallinson, David; Mutungi, Gabriel

2013-01-01

Glucocorticoids (GCs) are steroid hormones released from the adrenal gland in response to stress. They are also some of the most potent anti-inflammatory and immunosuppressive drugs currently in clinical use. They exert most of their physiological and pharmacological actions through the classical/genomic pathway. However, they also have rapid/non-genomic actions whose physiological and pharmacological functions are still poorly understood. Therefore, the primary aim of this study was to investigate the rapid/non-genomic effects of two widely prescribed glucocorticoids, beclomethasone dipropionate (BDP) and prednisolone acetate (PDNA), on force production in isolated, intact, mouse skeletal muscle fibre bundles. The results show that the effects of both GCs on maximum isometric force (Po) were fibre-type dependent. Thus, they increased Po in the slow-twitch fibre bundles without significantly affecting that of the fast-twitch fibre bundles. The increase in Po occurred within 10 min and was insensitive to the transcriptional inhibitor actinomycin D. Also, it was maximal at ∼250 nm and was blocked by the glucocorticoid receptor (GCR) inhibitor RU486 and a monoclonal anti-GCR, suggesting that it was mediated by a membrane (m) GCR. Both muscle fibre types expressed a cytosolic GCR. However, a mGCR was present only in the slow-twitch fibres. The receptor was more abundant in oxidative than in glycolytic fibres and was confined mainly to the periphery of the fibres where it co-localised with laminin. From these findings we conclude that the rapid/non-genomic actions of GCs are mediated by a mGCR and that they are physiologically/therapeutically beneficial, especially in slow-twitch muscle fibres. PMID:23878367

A membrane glucocorticoid receptor mediates the rapid/non-genomic actions of glucocorticoids in mammalian skeletal muscle fibres.

PubMed

Pérez, María Hernández-Alcalá; Cormack, Jonathan; Mallinson, David; Mutungi, Gabriel

2013-10-15

Glucocorticoids (GCs) are steroid hormones released from the adrenal gland in response to stress. They are also some of the most potent anti-inflammatory and immunosuppressive drugs currently in clinical use. They exert most of their physiological and pharmacological actions through the classical/genomic pathway. However, they also have rapid/non-genomic actions whose physiological and pharmacological functions are still poorly understood. Therefore, the primary aim of this study was to investigate the rapid/non-genomic effects of two widely prescribed glucocorticoids, beclomethasone dipropionate (BDP) and prednisolone acetate (PDNA), on force production in isolated, intact, mouse skeletal muscle fibre bundles. The results show that the effects of both GCs on maximum isometric force (Po) were fibre-type dependent. Thus, they increased Po in the slow-twitch fibre bundles without significantly affecting that of the fast-twitch fibre bundles. The increase in Po occurred within 10 min and was insensitive to the transcriptional inhibitor actinomycin D. Also, it was maximal at ∼250 nM and was blocked by the glucocorticoid receptor (GCR) inhibitor RU486 and a monoclonal anti-GCR, suggesting that it was mediated by a membrane (m) GCR. Both muscle fibre types expressed a cytosolic GCR. However, a mGCR was present only in the slow-twitch fibres. The receptor was more abundant in oxidative than in glycolytic fibres and was confined mainly to the periphery of the fibres where it co-localised with laminin. From these findings we conclude that the rapid/non-genomic actions of GCs are mediated by a mGCR and that they are physiologically/therapeutically beneficial, especially in slow-twitch muscle fibres.

Occurrence of Antimicrobial-Resistant Escherichia coli and Salmonella enterica in the Beef Cattle Production and Processing Continuum

PubMed Central

Agga, Getahun E.; Bosilevac, Joseph M.; Brichta-Harhay, Dayna M.; Shackelford, Steven D.; Wang, Rong; Wheeler, Tommy L.; Arthur, Terrance M.

2014-01-01

Specific concerns have been raised that third-generation cephalosporin-resistant (3GCr) Escherichia coli, trimethoprim-sulfamethoxazole-resistant (COTr) E. coli, 3GCr Salmonella enterica, and nalidixic acid-resistant (NALr) S. enterica may be present in cattle production environments, persist through beef processing, and contaminate final products. The prevalences and concentrations of these organisms were determined in feces and hides (at feedlot and processing plant), pre-evisceration carcasses, and final carcasses from three lots of fed cattle (n = 184). The prevalences and concentrations were further determined for strip loins from 103 of the carcasses. 3GCr Salmonella was detected on 7.6% of hides during processing and was not detected on the final carcasses or strip loins. NALr S. enterica was detected on only one hide. 3GCr E. coli and COTr E. coli were detected on 100.0% of hides during processing. Concentrations of 3GCr E. coli and COTr E. coli on hides were correlated with pre-evisceration carcass contamination. 3GCr E. coli and COTr E. coli were each detected on only 0.5% of final carcasses and were not detected on strip loins. Five hundred and 42 isolates were screened for extraintestinal pathogenic E. coli (ExPEC) virulence-associated markers. Only two COTr E. coli isolates from hides were ExPEC, indicating that fed cattle products are not a significant source of ExPEC causing human urinary tract infections. The very low prevalences of these organisms on final carcasses and their absence on strip loins demonstrate that current sanitary dressing procedures and processing interventions are effective against antimicrobial-resistant bacteria. PMID:25398858

Occurrence of Antimicrobial-Resistant Escherichia coli and Salmonella enterica in the Beef Cattle Production and Processing Continuum.

PubMed

Schmidt, John W; Agga, Getahun E; Bosilevac, Joseph M; Brichta-Harhay, Dayna M; Shackelford, Steven D; Wang, Rong; Wheeler, Tommy L; Arthur, Terrance M

2015-01-01

Specific concerns have been raised that third-generation cephalosporin-resistant (3GC(r)) Escherichia coli, trimethoprim-sulfamethoxazole-resistant (COT(r)) E. coli, 3GC(r) Salmonella enterica, and nalidixic acid-resistant (NAL(r)) S. enterica may be present in cattle production environments, persist through beef processing, and contaminate final products. The prevalences and concentrations of these organisms were determined in feces and hides (at feedlot and processing plant), pre-evisceration carcasses, and final carcasses from three lots of fed cattle (n = 184). The prevalences and concentrations were further determined for strip loins from 103 of the carcasses. 3GC(r) Salmonella was detected on 7.6% of hides during processing and was not detected on the final carcasses or strip loins. NAL(r) S. enterica was detected on only one hide. 3GC(r) E. coli and COT(r) E. coli were detected on 100.0% of hides during processing. Concentrations of 3GC(r) E. coli and COT(r) E. coli on hides were correlated with pre-evisceration carcass contamination. 3GC(r) E. coli and COT(r) E. coli were each detected on only 0.5% of final carcasses and were not detected on strip loins. Five hundred and 42 isolates were screened for extraintestinal pathogenic E. coli (ExPEC) virulence-associated markers. Only two COT(r) E. coli isolates from hides were ExPEC, indicating that fed cattle products are not a significant source of ExPEC causing human urinary tract infections. The very low prevalences of these organisms on final carcasses and their absence on strip loins demonstrate that current sanitary dressing procedures and processing interventions are effective against antimicrobial-resistant bacteria. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Do supernovae of type 1 paly a role in cosmic-ray production?

NASA Technical Reports Server (NTRS)

Shapiro, M. M.

1985-01-01

A model of cosmic-ray origin is suggested which aims to account for some salient features of the composition. Relative to solar abundances, the Galactic cosmic rays (GCR) are deficient in hydrogen and helim (H and He) by an order of magnitude when the two compositions are normalized at iron. Our conjectural model implicates supernovae of Type I (SN-I) as sources of some of the GCR. SN-I occur approximately as often as SN-II, through their genesis is thought to be different. Recent studies of nucleosynthesis in SN-I based on accreting white dwarfs, find that the elements from Si to Fe are produced copiously. On the other hand, SN-I are virtually devoid of hydrogen, and upper limits deduced for He are low. If SN-I contribute significantly to the pool of GCR by injecting energetic particles into the interstellar medium (ISM), then this could explain why the resulting GCR is relatively deficient in H and He. A test of the model is proposed, and difficulties are discussed.

Neutron density profile in the lunar subsurface produced by galactic cosmic rays

NASA Astrophysics Data System (ADS)

Ota, Shuya; Sihver, Lembit; Kobayashi, Shingo; Hasebe, Nobuyuki

Neutron production by galactic cosmic rays (GCR) in the lunar subsurface is very important when performing lunar and planetary nuclear spectroscopy and space dosimetry. Further im-provements to estimate the production with increased accuracy is therefore required. GCR, which is a main contributor to the neutron production in the lunar subsurface, consists of not only protons but also of heavy components such as He, C, N, O, and Fe. Because of that, it is important to precisely estimate the neutron production from such components for the lunar spectroscopy and space dosimetry. Therefore, the neutron production from GCR particles in-cluding heavy components in the lunar subsurface was simulated with the Particle and Heavy ion Transport code System (PHITS), using several heavy ion interaction models. This work presents PHITS simulations of the neutron density as a function of depth (neutron density profile) in the lunar subsurface and the results are compared with experimental data obtained by Apollo 17 Lunar Neutron Probe Experiment (LNPE). From our previous study, it has been found that the accuracy of the proton-induced neutron production models is the most influen-tial factor when performing precise calculations of neutron production in the lunar subsurface. Therefore, a benchmarking of proton-induced neutron production models against experimental data was performed to estimate and improve the precision of the calculations. It was found that the calculated neutron production using the best model of Cugnon Old (E < 3 GeV) and JAM (E > 3 GeV) gave up to 30% higher values than experimental results. Therefore, a high energy nuclear data file (JENDL-HE) was used instead of the Cugnon Old model at the energies below 3 GeV. Then, the calculated neutron density profile successfully reproduced the experimental data from LNPE within experimental errors of 15% (measurement) + 30% (systematic). In this presentation, we summarize and discuss our calculated results of neutron production in the lunar subsurface.

Space Weather Nowcasting of Atmospheric Ionizing Radiation for Aviation Safety

NASA Technical Reports Server (NTRS)

Mertens, Christopher J.; Wilson, John W.; Blattnig, Steve R.; Solomon, Stan C.; Wiltberger, J.; Kunches, Joseph; Kress, Brian T.; Murray, John J.

2007-01-01

There is a growing concern for the health and safety of commercial aircrew and passengers due to their exposure to ionizing radiation with high linear energy transfer (LET), particularly at high latitudes. The International Commission of Radiobiological Protection (ICRP), the EPA, and the FAA consider the crews of commercial aircraft as radiation workers. During solar energetic particle (SEP) events, radiation exposure can exceed annual limits, and the number of serious health effects is expected to be quite high if precautions are not taken. There is a need for a capability to monitor the real-time, global background radiations levels, from galactic cosmic rays (GCR), at commercial airline altitudes and to provide analytical input for airline operations decisions for altering flight paths and altitudes for the mitigation and reduction of radiation exposure levels during a SEP event. The Nowcast of Atmospheric Ionizing Radiation for Aviation Safety (NAIRAS) model is new initiative to provide a global, real-time radiation dosimetry package for archiving and assessing the biologically harmful radiation exposure levels at commercial airline altitudes. The NAIRAS model brings to bear the best available suite of Sun-Earth observations and models for simulating the atmospheric ionizing radiation environment. Observations are utilized from ground (neutron monitors), from the atmosphere (the METO analysis), and from space (NASA/ACE and NOAA/GOES). Atmospheric observations provide the overhead shielding information and the ground- and space-based observations provide boundary conditions on the GCR and SEP energy flux distributions for transport and dosimetry simulations. Dose rates are calculated using the parametric AIR (Atmospheric Ionizing Radiation) model and the physics-based HZETRN (High Charge and Energy Transport) code. Empirical models of the near-Earth radiation environment (GCR/SEP energy flux distributions and geomagnetic cut-off rigidity) are benchmarked against the physics-based CMIT (Coupled Magnetosphere- Ionosphere-Thermosphere) and SEP-trajectory models.

NAIRAS aircraft radiation model development, dose climatology, and initial validation.

PubMed

Mertens, Christopher J; Meier, Matthias M; Brown, Steven; Norman, Ryan B; Xu, Xiaojing

2013-10-01

[1] The Nowcast of Atmospheric Ionizing Radiation for Aviation Safety (NAIRAS) is a real-time, global, physics-based model used to assess radiation exposure to commercial aircrews and passengers. The model is a free-running physics-based model in the sense that there are no adjustment factors applied to nudge the model into agreement with measurements. The model predicts dosimetric quantities in the atmosphere from both galactic cosmic rays (GCR) and solar energetic particles, including the response of the geomagnetic field to interplanetary dynamical processes and its subsequent influence on atmospheric dose. The focus of this paper is on atmospheric GCR exposure during geomagnetically quiet conditions, with three main objectives. First, provide detailed descriptions of the NAIRAS GCR transport and dosimetry methodologies. Second, present a climatology of effective dose and ambient dose equivalent rates at typical commercial airline altitudes representative of solar cycle maximum and solar cycle minimum conditions and spanning the full range of geomagnetic cutoff rigidities. Third, conduct an initial validation of the NAIRAS model by comparing predictions of ambient dose equivalent rates with tabulated reference measurement data and recent aircraft radiation measurements taken in 2008 during the minimum between solar cycle 23 and solar cycle 24. By applying the criterion of the International Commission on Radiation Units and Measurements (ICRU) on acceptable levels of aircraft radiation dose uncertainty for ambient dose equivalent greater than or equal to an annual dose of 1 mSv, the NAIRAS model is within 25% of the measured data, which fall within the ICRU acceptable uncertainty limit of 30%. The NAIRAS model predictions of ambient dose equivalent rate are generally within 50% of the measured data for any single-point comparison. The largest differences occur at low latitudes and high cutoffs, where the radiation dose level is low. Nevertheless, analysis suggests that these single-point differences will be within 30% when a new deterministic pion-initiated electromagnetic cascade code is integrated into NAIRAS, an effort which is currently underway.

NAIRAS aircraft radiation model development, dose climatology, and initial validation

NASA Astrophysics Data System (ADS)

Mertens, Christopher J.; Meier, Matthias M.; Brown, Steven; Norman, Ryan B.; Xu, Xiaojing

2013-10-01

The Nowcast of Atmospheric Ionizing Radiation for Aviation Safety (NAIRAS) is a real-time, global, physics-based model used to assess radiation exposure to commercial aircrews and passengers. The model is a free-running physics-based model in the sense that there are no adjustment factors applied to nudge the model into agreement with measurements. The model predicts dosimetric quantities in the atmosphere from both galactic cosmic rays (GCR) and solar energetic particles, including the response of the geomagnetic field to interplanetary dynamical processes and its subsequent influence on atmospheric dose. The focus of this paper is on atmospheric GCR exposure during geomagnetically quiet conditions, with three main objectives. First, provide detailed descriptions of the NAIRAS GCR transport and dosimetry methodologies. Second, present a climatology of effective dose and ambient dose equivalent rates at typical commercial airline altitudes representative of solar cycle maximum and solar cycle minimum conditions and spanning the full range of geomagnetic cutoff rigidities. Third, conduct an initial validation of the NAIRAS model by comparing predictions of ambient dose equivalent rates with tabulated reference measurement data and recent aircraft radiation measurements taken in 2008 during the minimum between solar cycle 23 and solar cycle 24. By applying the criterion of the International Commission on Radiation Units and Measurements (ICRU) on acceptable levels of aircraft radiation dose uncertainty for ambient dose equivalent greater than or equal to an annual dose of 1 mSv, the NAIRAS model is within 25% of the measured data, which fall within the ICRU acceptable uncertainty limit of 30%. The NAIRAS model predictions of ambient dose equivalent rate are generally within 50% of the measured data for any single-point comparison. The largest differences occur at low latitudes and high cutoffs, where the radiation dose level is low. Nevertheless, analysis suggests that these single-point differences will be within 30% when a new deterministic pion-initiated electromagnetic cascade code is integrated into NAIRAS, an effort which is currently underway.

NAIRAS aircraft radiation model development, dose climatology, and initial validation

PubMed Central

Mertens, Christopher J; Meier, Matthias M; Brown, Steven; Norman, Ryan B; Xu, Xiaojing

2013-01-01

[1] The Nowcast of Atmospheric Ionizing Radiation for Aviation Safety (NAIRAS) is a real-time, global, physics-based model used to assess radiation exposure to commercial aircrews and passengers. The model is a free-running physics-based model in the sense that there are no adjustment factors applied to nudge the model into agreement with measurements. The model predicts dosimetric quantities in the atmosphere from both galactic cosmic rays (GCR) and solar energetic particles, including the response of the geomagnetic field to interplanetary dynamical processes and its subsequent influence on atmospheric dose. The focus of this paper is on atmospheric GCR exposure during geomagnetically quiet conditions, with three main objectives. First, provide detailed descriptions of the NAIRAS GCR transport and dosimetry methodologies. Second, present a climatology of effective dose and ambient dose equivalent rates at typical commercial airline altitudes representative of solar cycle maximum and solar cycle minimum conditions and spanning the full range of geomagnetic cutoff rigidities. Third, conduct an initial validation of the NAIRAS model by comparing predictions of ambient dose equivalent rates with tabulated reference measurement data and recent aircraft radiation measurements taken in 2008 during the minimum between solar cycle 23 and solar cycle 24. By applying the criterion of the International Commission on Radiation Units and Measurements (ICRU) on acceptable levels of aircraft radiation dose uncertainty for ambient dose equivalent greater than or equal to an annual dose of 1 mSv, the NAIRAS model is within 25% of the measured data, which fall within the ICRU acceptable uncertainty limit of 30%. The NAIRAS model predictions of ambient dose equivalent rate are generally within 50% of the measured data for any single-point comparison. The largest differences occur at low latitudes and high cutoffs, where the radiation dose level is low. Nevertheless, analysis suggests that these single-point differences will be within 30% when a new deterministic pion-initiated electromagnetic cascade code is integrated into NAIRAS, an effort which is currently underway. PMID:26213513

2nd-order optical model of the isotopic dependence of heavy ion absorption cross sections for radiation transport studies

NASA Astrophysics Data System (ADS)

Cucinotta, Francis A.; Yan, Congchong; Saganti, Premkumar B.

2018-01-01

Heavy ion absorption cross sections play an important role in radiation transport codes used in risk assessment and for shielding studies of galactic cosmic ray (GCR) exposures. Due to the GCR primary nuclei composition and nuclear fragmentation leading to secondary nuclei heavy ions of charge number, Z with 3 ≤ Z ≥ 28 and mass numbers, A with 6 ≤ A ≥ 60 representing about 190 isotopes occur in GCR transport calculations. In this report we describe methods for developing a data-base of isotopic dependent heavy ion absorption cross sections for interactions. Calculations of a 2nd-order optical model solution to coupled-channel solutions to the Eikonal form of the nucleus-nucleus scattering amplitude are compared to 1st-order optical model solutions. The 2nd-order model takes into account two-body correlations in the projectile and target ground-states, which are ignored in the 1st-order optical model. Parameter free predictions are described using one-body and two-body ground state form factors for the isotopes considered and the free nucleon-nucleon scattering amplitude. Root mean square (RMS) matter radii for protons and neutrons are taken from electron and muon scattering data and nuclear structure models. We report on extensive comparisons to experimental data for energy-dependent absorption cross sections for over 100 isotopes of elements from Li to Fe interacting with carbon and aluminum targets. Agreement between model and experiments are generally within 10% for the 1st-order optical model and improved to less than 5% in the 2nd-order optical model in the majority of comparisons. Overall the 2nd-order optical model leads to a reduction in absorption compared to the 1st-order optical model for heavy ion interactions, which influences estimates of nuclear matter radii.

The Ectopic Expression of the Wheat Puroindoline Genes Increase Germ Size and Seed Oil Content in Transgenic Corn

PubMed Central

Zhang, Jinrui; Martin, John M.; Beecher, Brian; Lu, Chaofu; Hannah, L. Curtis; Wall, Michael L.; Altosaar, Illimar; Giroux, Michael J.

2014-01-01

Plant oil content and composition improvement is a major goal of plant breeding and biotechnology. The Puroindoline a and b (PINA and PINB) proteins together control whether wheat seeds are soft or hard textured and share a similar structure to that of plant non-specific lipid-transfer proteins. Here we transformed corn (Zea mays L.) with the wheat (Triticum aestivum L.) puroindoline genes (Pina and Pinb) to assess their effects upon seed oil content and quality. Pina and Pinb coding sequences were introduced into corn under the control of a corn Ubiquitin promoter. Three Pina/Pinb expression positive transgenic events were evaluated over two growing seasons. The results showed that Pin expression increased germ size significantly without negatively impacting seed size. Germ yield increased 33.8% while total seed oil content was increased by 25.23%. Seed oil content increases were primarily the result of increased germ size. This work indicates that higher oil content corn hybrids having increased food or feed value could be produced via puroindoline expression. PMID:20725765

Modeling and Experimental Study of Forbush Effects of Galactic Cosmic Rays

NASA Astrophysics Data System (ADS)

Alania, Michael V.; Szabelski, J.; Wawrzynczak, A.

2003-07-01

temporal changes of the rigidity spectrum of the sporadic and recurrent Forbush effects of galactic cosmic rays (GCR) have been studied using neutron monitors data. An attempt to find a relationship between the rigidity spectrum exponent γ of the Forbush effects (δD/D(R) ∝ R-γ , where R is the rigidity of GCR particles) and an exponent ν of the power spectral density (PSD) of the fluctuations of the strength of the interplanetary magnetic field (IMF) (PSD ∝ f-ν , where f is the frequency) has been made. EXPERIMENTAL DATA AND METHOD OF INVESTIGATION. An attempt to find a relationship between the rigidity spectrum exponent γ of the Forbush effects [1] (δ D/D(R) ∝ R-γ , where R is the rigidity of GCR particles) and an exponent ν of the PSD of the fluctuations of the strength of the IMF has been made. Data of neutron super monitors and the IMF's Bx , By , and Bz components have been used to study peculiarities of two great sporadic Forbush effects (9-23 July 1982 and 9-29 July 2000) and one recurrent Forbush effect of the 1-16 September 1996 (figures 1ab c). It is well known that one of the ma jor parameters for the characterizing of the Forbush effects of GCR is the rigidity spectrum of the GCR intensity variations, hereafter called the rigidity spectrum of Forbush effect (δ D(R)/D(R ) = A R-γ , where R is the rigidity of GCR particles and A is the power). The rigidity spectrum of the Forbush effects has been calculated using the data of neutron super monitors and the method presented, e.g. in [2,3]. There was assumed: δ D(R)/D(R) = A R-γ for R≤Rmax . And δ D(R)/D(R) = 0 for R>Rmax. Here Rmax is the upper limiting rigidity beyond which the Forbush effect of GCR intensity vanishes. Results of calculations of γ based on daily means of data for the sporadic Forbush effects, 9-23 July 1982 (14 stations), 9-29 July 2000 (11 stations) and for the recurrent Forbush effect of 1-16 September 1996 (7 stations) are presented in the figures 1def. RESULTS, PHYSICAL MODEL AND DISCUSSION. It is seen from the fig.1de that the rigidity spectrum of the sporadic Forbush effects are soft at the phases of the decreasing of GCR intensity, while that

Simulation of major space particles toward selected materials in a near-equatorial low earth orbit

NASA Astrophysics Data System (ADS)

Suparta, Wayan; Zulkeple, Siti Katrina

2017-05-01

A low earth orbit near the equator (LEO-NEqO) is exposed to the highest energies from galactic cosmic rays (GCR) and from trapped protons with a wide range of energies. Moreover, GCR fluxes were seen to be the highest in 2009 to 2010 when communication belonging to the RazakSAT-1 satellite was believed to have been lost. Hence, this study aimed to determine the influence of the space environment toward the operation of LEO-NEqO satellites by investigating the behavior of major space particles toward satellite materials. The space environment was referred to GCR protons and trapped protons. Their fluxes were obtained from the Space Environment Information System (SPENVIS) and their tracks were simulated through three materials using a simulation program called Geometry and Tracking (Geant4). The materials included aluminum (Al), gallium arsenide (GaAs) and silicon (Si). Then the total ionizing dose (TID) and non-ionizing dose (NIEL) were calculated for a three-year period. Simulations showed that GCR traveled at longer tracks and produced more secondary radiation than trapped protons. Al turned out to receive the lowest total dose, while GaAs showed to be susceptible toward GCR than Si. However, trapped protons contributed the most in spacecraft doses where Si received the highest doses. Finally, the comparison between two Geant4 programs revealed the estimated doses differed at <18%.

Search for cosmogenic Ar-42 in meteorites

NASA Astrophysics Data System (ADS)

Cini Castagnoli, G.; Cane, D.; Taricco, C.; Bhandari, N.

2003-04-01

We have evidence for decreasing galactic cosmic ray (GCR) flux in the past 3 centuries by a factor about two [1]. The measurements of the activity of cosmogenic 44Ti (T1/2 = 59.2 y) produced by GCR in stony meteorites that fell during the last two centuries are in good agreement with the calculated values and validate the decreasing trend of GCR flux. The measurements were obtained by an hyperpure (372 cm3) Ge-NaI(Tl) spectrometer operating in the Monte dei Cappuccini laboratory in Torino[2]. To further improve upon statistical precision of 44Ti data and also to be able to measure the 42Ar (T1/2 = 33 y) which is produced in even smaller amounts by GCR in meteorites, we have set up in the same laboratory a larger (581 cm3) hyperpure Ge detector operating in coincidence with a 100 kg NaI(Tl) crystal assembly. This should enable us to confirm the above results about GCR variations. We wish to acknowledge our deep gratitude to professor Bonino, deceased on September 29, 2002, to whom the assemblage of the new equipment is due. [1] G. Bonino, G. Cini Castagnoli, D. Cane, C. Taricco and N. Bhandari,Proc. XXVII Intern. Cosmic Ray Conf. (Hamburg, 2001) 3769-3772. [2] Bonino G., Cini Castagnoli G., Cane D., Taricco C., Bhandari N, textit {34th COSPAR Sci. Ass. Houston 2002 (Adv. Space Res.)}, in press

Assessing the experience in complex hepatopancreatobiliary surgery among graduating chief residents: Is the operative experience enough?

PubMed Central

Sachs, Teviah E.; Ejaz, Aslam; Weiss, Matthew; Spolverato, Gaya; Ahuja, Nita; Makary, Martin A.; Wolfgang, Christopher L.; Hirose, Kenzo; Pawlik, Timothy M.

2015-01-01

Introduction Resident operative autonomy and case volume is associated with posttraining confidence and practice plans. Accreditation Council for Graduate Medical Education requirements for graduating general surgery residents are four liver and three pancreas cases. We sought to evaluate trends in resident experience and autonomy for complex hepatopancreatobiliary (HPB) surgery over time. Methods We queried the Accreditation Council for Graduate Medical Education General Surgery Case Log (2003–2012) for all cases performed by graduating chief residents (GCR) relating to liver, pancreas, and the biliary tract (HPB); simple cholecystectomy was excluded. Mean (±SD), median [10th–90th percentiles] and maximum case volumes were compared from 2003 to 2012 using R2 for all trends. Results A total of 252,977 complex HPB cases (36% liver, 43% pancreas, 21% biliary) were performed by 10,288 GCR during the 10-year period examined (Mean = 24.6 per GCR). Of these, 57% were performed during the chief year, whereas 43% were performed as postgraduate year 1–4. Only 52% of liver cases were anatomic resections, whereas 71% of pancreas cases were major resections. Total number of cases increased from 22,516 (mean = 23.0) in 2003 to 27,191 (mean = 24.9) in 2012. During this same time period, the percentage of HPB cases that were performed during the chief year decreased by 7% (liver: 13%, pancreas 8%, biliary 4%). There was an increasing trend in the mean number of operations (mean ± SD) logged by GCR on the pancreas (9.1 ± 5.9 to 11.3 ± 4.3; R2 = .85) and liver (8.0 ± 5.9 to 9.4 ± 3.4; R2 = .91), whereas those for the biliary tract decreased (5.9 ± 2.5 to 3.8 ± 2.1; R2 = .96). Although the median number of cases [10th:90th percentile] increased slightly for both pancreas (7.0 [4.0:15] to 8.0 [4:20]) and liver (7.0 [4:13] to 8.0 [5:14]), the maximum number of cases preformed by any given GCR remained stable for pancreas (51 to 53; R2 = .18), but increased for liver (38 to 45; R2 = .32). The median number of HPB cases that GCR performed as teaching assistants (TAs) remained at zero during this time period. The 90th percentile of cases performed as TA was less than two for both pancreas and liver. Conclusion Roughly one-half of GCR have performed fewer than 10 cases in each of the liver, pancreas, or biliary categories at time of completion of residency. Although the mean number of complex liver and pancreatic operations performed by GCR increased slightly, the median number remained low, and the number of TA cases was virtually zero. Most GCR are unlikely to be prepared to perform complex HPB operations. PMID:24953270

Badhwar-O'Neil 2007 Galactic Cosmic Ray (GCR) Model Using Advanced Composition Explorer (ACE) Measurements for Solar Cycle 23

NASA Technical Reports Server (NTRS)

ONeill, P. M.

2007-01-01

Advanced Composition Explorer (ACE) satellite measurements of the galactic cosmic ray flux and correlation with the Climax Neutron Monitor count over Solar Cycle 23 are used to update the Badhwar O'Neill Galactic Cosmic Ray (GCR) model.

Occurrence of antimicrobial-resistant Escherichia coli and Salmonella enterica in the beef cattle production and processing continuum

USDA-ARS?s Scientific Manuscript database

Specific concerns have been raised that 3rd-generation cephalosporin-resistant (3GCr) Escherichia coli, trimethoprim-sulfamethoxazole-resistant (COTr) E. coli, 3GCr Salmonella enterica, and nalidixic acid-resistant (NALr) S. enterica, may be present in cattle production environments, persist through...

Antimicrobial-resistant fecal bacteria from ceftiofur-treated and nonantimicrobial-treated comingled beef cows at a cow-calf operation

USDA-ARS?s Scientific Manuscript database

We compared the occurrences of 3rd-generation cephalosporin-resistant (3GCr ), tetracycline-resistant (TETr) and trimethoprim-sulfamethoxazole-resistant (COTr ) Escherichia coli, 3GCr Salmonella enterica, nalidixic acid-resistant (NALr) S. enterica and erythromycin-resistant (ERYr) enterococci from ...

Homeland security in the C. elegans germ line: insights into the biogenesis and function of piRNAs.

PubMed

Kasper, Dionna M; Gardner, Kathryn E; Reinke, Valerie

2014-01-01

While most eukaryotic genomes contain transposable elements that can provide select evolutionary advantages to a given organism, failure to tightly control the mobility of such transposable elements can result in compromised genomic integrity of both parental and subsequent generations. Together with the Piwi subfamily of Argonaute proteins, small, non-coding Piwi-interacting RNAs (piRNAs) primarily function in the germ line to defend the genome against the potentially deleterious effects that can be caused by transposition. Here, we describe recent discoveries concerning the biogenesis and function of piRNAs in the nematode Caenorhabditis elegans, illuminating how the faithful production of these mature species can impart a robust defense mechanism for the germ line to counteract problems caused by foreign genetic elements across successive generations by contributing to the epigenetic memory of non-self vs. self.

Early Energetic Particle Irradiation of the HED Parent Body Regolith

NASA Technical Reports Server (NTRS)

Bogard, D. D.; Garrison, D. H.; Rao, M. N.

1996-01-01

Previous studies have shown that many individual grains within the dark phase of the Kapoeta howardite were irradiated with energetic particles while residing on the surface of the early HED regolith. Particle tracks in these grains vary in density by more than an order of magnitude and undoubtedly were formed by energetic heavy (Fe) ions associated with early solar flares. Early Irradiation of HED Regolith: Concentrations of excess Ne alone are not sufficient to decide between competing galactic and solar irradiation models. However, from recent studies of depth samples of oriented lunar rocks, we have shown that the cosmogenic 21-Ne/22-Ne ratio produced in feldspar differs substantially between Galactic Cosmic Radiation (GCR) and solar protons, and that this difference is exactly that predicted from cross-section data. Using Ne literature data and new isotopic data we obtained on acid-etched, separated feldspar from both the light and dark phases of Kapoeta, we derive 21-Ne/22-Ne = 0.80 for the recent GCR irradiation and 21-Ne/22-Ne = 0.68 for the early regolith irradiation. This derived ratio indicates that the early Ne production in the regolith occurred by both galactic and solar protons. If we adopt a likely one-component regolith model in which all grains were exposed to galactic protons but individual grains had variable exposure to solar protons, we estimate that this early GCR irradiation lasted for about 3-6 m.y. More complex two-component regolith models involving separate solar and galactic irradiation would permit this GCR age to be longer. Higher-energy solar protons would permit the GCR to be longer. Higher-energy solar protons would permit the GCR age to be shorter. Further, cosmogenic 126(Xe) in Kapoeta dark is no more than a factor of about 2 higher than that observed in Kapoeta light. Because 126(Xe) can only be formed by galactic protons and not solar protons, these data support a short GCR irradiation for the HED regolith. This would also be the maximum time peRiod for the solar irradiation. Various asteroidal regolith models, based on Monte Carlo modeling of impact rates as a function of size and on irradiation features of meteorites, predict surface exposure times of about 0.1 to 10 m.y., and depend on such factors as gravity, rock mechanical properties, and micrometeoroid flux. Because the depth at which solar Fe tracks are produced (is much less than 1 micrometer) is much less than the depth at which Solar Cosmic Rays (SCR) Ne is produced (about 1 cm), for a reasonably well-stirred HED regolith the "surface exposure time" for SCR 21-Ne production should be significantly longer than that for solar tracks and some other surface irradiation features. Enhanced Solar Proton Irradiation: For bulk samples of Kapoeta dark feldspar and a one-component regolith model, the derived ratio of 21-Ne/22-Ne = 0.68 implies that the early production ratio of SCR 21-Ne to GCR 21-Ne was about 0.5-1.5. This ratio is independent of any assumptions about the fraction of dark grains that are irradiated or of the variability in the degree of solar irradiation among grains. The 21-Ne SCR/GCR ratio indirectly derived from bulk Kapoeta pyroxene is somewhat larger, as is the ratio derived for simple two-component regolith models. Individual feldspar grains that were extensively solar irradiated would require even larger 21-Ne SCR/GCR production ratios. In contrast, the theoretical SCR/GCR production ratio for lunar feldspar with 0 g/CM2 shield ing is is less than or equal to 2, and the lowest ratio observed in near-surface samples of lunar anorthosites is less than or equal to 1. Considering the greater solar distance of Vesta (compared to the Moon), the likelihood that SCR 21-Ne was acquired under some shielding where production rates are lower, and the likelihood that the exposure time to galactic protons exceeded the exposure time to solar protons because of their very different penetration depths, the 21-Ne SCR/GCR production ratio on the HED parent body was probably < 0.1. The relatively large difference between the derived 21-Ne SCR/GCR ratio in Kapoeta dark feldspar and the estimated production ratio strongly indicates that the early solar irradiation involved a flux -20-50x the recent solar flux. This enhanced proton flux was probably associated with an overall greater solar activity in the first approximately 10(exp 7) to 10(exp 8) years of solar history.

The HOX genes are expressed, in vivo, in human tooth germs: in vitro cAMP exposure of dental pulp cells results in parallel HOX network activation and neuronal differentiation.

PubMed

D'Antò, Vincenzo; Cantile, Monica; D'Armiento, Maria; Schiavo, Giulia; Spagnuolo, Gianrico; Terracciano, Luigi; Vecchione, Raffaela; Cillo, Clemente

2006-03-01

Homeobox-containing genes play a crucial role in odontogenesis. After the detection of Dlx and Msx genes in overlapping domains along maxillary and mandibular processes, a homeobox odontogenic code has been proposed to explain the interaction between different homeobox genes during dental lamina patterning. No role has so far been assigned to the Hox gene network in the homeobox odontogenic code due to studies on specific Hox genes and evolutionary considerations. Despite its involvement in early patterning during embryonal development, the HOX gene network, the most repeat-poor regions of the human genome, controls the phenotype identity of adult eukaryotic cells. Here, according to our results, the HOX gene network appears to be active in human tooth germs between 18 and 24 weeks of development. The immunohistochemical localization of specific HOX proteins mostly concerns the epithelial tooth germ compartment. Furthermore, only a few genes of the network are active in embryonal retromolar tissues, as well as in ectomesenchymal dental pulp cells (DPC) grown in vitro from adult human molar. Exposure of DPCs to cAMP induces the expression of from three to nine total HOX genes of the network in parallel with phenotype modifications with traits of neuronal differentiation. Our observations suggest that: (i) by combining its component genes, the HOX gene network determines the phenotype identity of epithelial and ectomesenchymal cells interacting in the generation of human tooth germ; (ii) cAMP treatment activates the HOX network and induces, in parallel, a neuronal-like phenotype in human primary ectomesenchymal dental pulp cells. 2005 Wiley-Liss, Inc.

Simulations of GCR interactions within planetary bodies using GEANT4

NASA Astrophysics Data System (ADS)

Mesick, K.; Feldman, W. C.; Stonehill, L. C.; Coupland, D. D. S.

2017-12-01

On planetary bodies with little to no atmosphere, Galactic Cosmic Rays (GCRs) can hit the body and produce neutrons primarily through nuclear spallation within the top few meters of the surfaces. These neutrons undergo further nuclear interactions with elements near the planetary surface and some will escape the surface and can be detected by landed or orbiting neutron radiation detector instruments. The neutron leakage signal at fast neutron energies provides a measure of average atomic mass of the near-surface material and in the epithermal and thermal energy ranges is highly sensitive to the presence of hydrogen. Gamma-rays can also escape the surface, produced at characteristic energies depending on surface composition, and can be detected by gamma-ray instruments. The intra-nuclear cascade (INC) that occurs when high-energy GCRs interact with elements within a planetary surface to produce the leakage neutron and gamma-ray signals is highly complex, and therefore Monte Carlo based radiation transport simulations are commonly used for predicting and interpreting measurements from planetary neutron and gamma-ray spectroscopy instruments. In the past, the simulation code that has been widely used for this type of analysis is MCNPX [1], which was benchmarked against data from the Lunar Neutron Probe Experiment (LPNE) on Apollo 17 [2]. In this work, we consider the validity of the radiation transport code GEANT4 [3], another widely used but open-source code, by benchmarking simulated predictions of the LPNE experiment to the Apollo 17 data. We consider the impact of different physics model options on the results, and show which models best describe the INC based on agreement with the Apollo 17 data. The success of this validation then gives us confidence in using GEANT4 to simulate GCR-induced neutron leakage signals on Mars in relevance to a re-analysis of Mars Odyssey Neutron Spectrometer data. References [1] D.B. Pelowitz, Los Alamos National Laboratory, LA-CP-05-0369, 2005. [2] G.W. McKinney et al, Journal of Geophysics Research, 111, E06004, 2006. [3] S. Agostinelli et al, Nuclear Instrumentation and Methods A, 506, 2003.

Evaluating Shielding Effectiveness for Reducing Space Radiation Cancer Risks

NASA Technical Reports Server (NTRS)

Cucinotta, Francis A.; Kim, Myung-Hee Y.; Ren, Lei

2007-01-01

We discuss calculations of probability distribution functions (PDF) representing uncertainties in projecting fatal cancer risk from galactic cosmic rays (GCR) and solar particle events (SPE). The PDF s are used in significance tests of the effectiveness of potential radiation shielding approaches. Uncertainties in risk coefficients determined from epidemiology data, dose and dose-rate reduction factors, quality factors, and physics models of radiation environments are considered in models of cancer risk PDF s. Competing mortality risks and functional correlations in radiation quality factor uncertainties are treated in the calculations. We show that the cancer risk uncertainty, defined as the ratio of the 95% confidence level (CL) to the point estimate is about 4-fold for lunar and Mars mission risk projections. For short-stay lunar missions (<180 d), SPE s present the most significant risk, however one that is mitigated effectively by shielding, especially for carbon composites structures with high hydrogen content. In contrast, for long duration lunar (>180 d) or Mars missions, GCR risks may exceed radiation risk limits, with 95% CL s exceeding 10% fatal risk for males and females on a Mars mission. For reducing GCR cancer risks, shielding materials are marginally effective because of the penetrating nature of GCR and secondary radiation produced in tissue by relativistic particles. At the present time, polyethylene or carbon composite shielding can not be shown to significantly reduce risk compared to aluminum shielding based on a significance test that accounts for radiobiology uncertainties in GCR risk projection.

GCR Simulator Reference Field and a Spectral Approach for Laboratory Simulation

NASA Technical Reports Server (NTRS)

Slaba, Tony C.; Blattnig, Steve R.; Norbury, John W.; Rusek, Adam; La Tessa, Chiara; Walker, Steven A.

2015-01-01

The galactic cosmic ray (GCR) simulator at the NASA Space Radiation Laboratory (NSRL) is intended to deliver the broad spectrum of particles and energies encountered in deep space to biological targets in a controlled laboratory setting. In this work, certain aspects of simulating the GCR environment in the laboratory are discussed. Reference field specification and beam selection strategies at NSRL are the main focus, but the analysis presented herein may be modified for other facilities. First, comparisons are made between direct simulation of the external, free space GCR field and simulation of the induced tissue field behind shielding. It is found that upper energy constraints at NSRL limit the ability to simulate the external, free space field directly (i.e. shielding placed in the beam line in front of a biological target and exposed to a free space spectrum). Second, variation in the induced tissue field associated with shielding configuration and solar activity is addressed. It is found that the observed variation is likely within the uncertainty associated with representing any GCR reference field with discrete ion beams in the laboratory, given current facility constraints. A single reference field for deep space missions is subsequently identified. Third, an approach for selecting beams at NSRL to simulate the designated reference field is presented. Drawbacks of the proposed methodology are discussed and weighed against alternative simulation strategies. The neutron component and track structure characteristics of the simulated field are discussed in this context.

Depth-dose equivalent relationship for cosmic rays at various solar minima

NASA Technical Reports Server (NTRS)

Badhwar, G. D.; Cucinotta, F. A.; O'Neill, P. M.

1993-01-01

Galactic cosmic rays (GCR) pose a serious radiation hazard for long-duration missions. In designing a lunar habitat or a Mars transfer vehicle, the radiation exposure determines the GCR shielding thickness, and hence the weight of spacecraft. Using the spherically symmetric diffusion theory of the solar modulation of GCR, and data on the differential energy spectra of H, He, O, and Fe, from 1965 to 1989, it has been shown that (1) the flux is determined by the diffusion parameter which is a function of the time in the solar cycle, and (2) the fluxes in the 1954 and 1976-1977 solar minima were similar and higher than those in 1965. In this paper, we have extended the spherical solar modulation theory back to 1954. The 1954-1955 GCR flux was nearly the same as that from 1976 to 1977; the 1965 flux values were nearly the same as those in 1986. Using this theory we have obtained the GCR spectra for all the nuclei, and calculated the depth dose as a function of Al thickness. It is shown that the shielding required to stay below 0.5 Sv is 17.5 -3/+8 g/sq cm of Al, and 9 -1.5/+5 g/sq cm to stay below 0.6 Sv. The calculated dose equivalent using the ICRP 60 values for quality factors is about 15 percent higher than that calculated using the ICRP 26 value.

Radiation equivalent dose simulations for long-term interplanetary flights

NASA Astrophysics Data System (ADS)

Dobynde, M. I.; Drozdov, A.; Shprits, Y. Y.

2016-12-01

Cosmic particle radiation is a limiting factor for the human interplanetary flights. The unmanned flights inside heliosphere and human flights inside of magnetosphere tend to become a routine procedure, whereas there have been only few shot term human flights out of it (Apollo missions 1969-1972) with maximum duration less than a month. Long-term human flights set much higher requirements to the radiation shielding, primarily because of long exposition to cosmic radiation. Inside the helosphere there are two main sources of cosmic radiation: galactic cosmic rays (GCR) and soalr particle events (SPE). GCR come from the outside of heliosphere forming a background of overall radiation that affects the spacecraft. The intensity of GCR is varied according to solar activity, increasing with solar activity decrease and backward, with the modulation time (time between nearest maxima) of 11 yeas. SPE are shot term events, comparing to GCR modulation time, but particle fluxes are much more higher. The probability of SPE increases with the increase of solar activity. Time dependences of the intensity of these two components encourage looking for a time window of flight, when intensity and effect of GCR and SPE would be minimized. Combining GEANT4 Monte Carlo simulations with time dependent model of GCR spectra and data on SPE spectra we show the time dependence of the radiation dose in an anthropomorphic human phantom inside the shielding capsule. Different types of particles affect differently on the human providing more or less harm to the tissues. We use quality factors to recalculate absorbed dose into biological equivalent dose, which give more information about risks for astronaut's health. Incident particles provide a large amount of secondary particles while propagating through the shielding capsule. We try to find an optimal combination of shielding material and thickness, that will effectively decrease the incident particle energy, at the same time minimizing flow of secondary induced particles and minimizing most harmful particle types flows.

GCR flux reconstruction during the last three centuries validated by the Ti-44 in meteorites and Be-10 in ice

NASA Astrophysics Data System (ADS)

Cini Castagnoli, G.; Cane, D.; Taricco, C.; Bhandari, N.

2003-04-01

In a previous work [1] we deduced that during prolonged minima of solar activity since 1700 the galactic cosmic rays (GCR) flux was much higher (˜2 times) respect to what we can infer from GCR modulation deduced solely by the Sunspot Number series. This flux was higher respect to what we observe in the last decades by Neutron Monitor or balloon and spacecraft-borne detectors and confirmed by the three fresh-fall meteorites that we have measured during solar cycle 22. Recently we have deduced the GCR annual mean spectra for the last 300 years [2], starting from the open solar magnetic flux proposed by Solanki et al. [3]. Utilizing the GCR flux we have calculated the 44Ti (T1/2 = 59.2 y) activity in meteorites taking into account the cross sections for its production from the main target element Fe and Ni. We compare the calculated activity with our measurements of the cosmogenic 44Ti in different chondrites fell in the period 1810-1997. The results are in close agreement both in phase and amplitude. The same procedure has been adopted for calculating the production rate of 10Be in atmosphere. Normalizing to the concentration in ice in the solar cycles 20 and 21 we obtain a good agreement with the 10Be profile in Dye3 core [4]. These results demonstrate that our inference of the GCR flux in the past 300 years is reliable. [1] Bonino G., Cini Castagnoli G., Bhandari N., Taricco C., textit {Science}, 270, 1648, 1995 [2] Bonino G., Cini Castagnoli G., Cane D., Taricco C. and Bhandari N., textit {Proc. XXVII Intern. Cosmic Ray Conf.} (Hamburg, 2001) 3769-3772. [3] Solanki S.K., Schüssler M. and Fligge M.,Nature, 408, 445, 2000 [4] Beer J. et al., private communication

Reference field specification and preliminary beam selection strategy for accelerator-based GCR simulation

NASA Astrophysics Data System (ADS)

Slaba, Tony C.; Blattnig, Steve R.; Norbury, John W.; Rusek, Adam; La Tessa, Chiara

2016-02-01

The galactic cosmic ray (GCR) simulator at the NASA Space Radiation Laboratory (NSRL) is intended to deliver the broad spectrum of particles and energies encountered in deep space to biological targets in a controlled laboratory setting. In this work, certain aspects of simulating the GCR environment in the laboratory are discussed. Reference field specification and beam selection strategies at NSRL are the main focus, but the analysis presented herein may be modified for other facilities and possible biological considerations. First, comparisons are made between direct simulation of the external, free space GCR field and simulation of the induced tissue field behind shielding. It is found that upper energy constraints at NSRL limit the ability to simulate the external, free space field directly (i.e. shielding placed in the beam line in front of a biological target and exposed to a free space spectrum). Second, variation in the induced tissue field associated with shielding configuration and solar activity is addressed. It is found that the observed variation is likely within the uncertainty associated with representing any GCR reference field with discrete ion beams in the laboratory, given current facility constraints. A single reference field for deep space missions is subsequently identified. Third, a preliminary approach for selecting beams at NSRL to simulate the designated reference field is presented. This approach is not a final design for the GCR simulator, but rather a single step within a broader design strategy. It is shown that the beam selection methodology is tied directly to the reference environment, allows facility constraints to be incorporated, and may be adjusted to account for additional constraints imposed by biological or animal care considerations. The major biology questions are not addressed herein but are discussed in a companion paper published in the present issue of this journal. Drawbacks of the proposed methodology are discussed and weighed against alternative simulation strategies.

Badhwar - O'Neill galactic cosmic ray model update based on Advanced Composition Explorer (ACE) energy spectra from 1997 to present

NASA Astrophysics Data System (ADS)

O'Neill, P.

Accurate knowledge of the interplanetary Galactic Cosmic Ray (GCR) environment is critical to planning and operating manned space flight to the moon and beyond. In the early 1990's Badhwar and O'Neill developed a GCR model based on balloon and satellite data from 1954 to 1992. This model accurately accounts for solar modulation of each element (hydrogen -- iron) by propagating the Local Interplanetary Spectrum (LIS) of each element through the heliosphere by solving the Fokker -- Planck diffusion, convection, energy loss boundary value problem. A single value of the deceleration parameter describes the modulation of each of the elements and determines the GCR energy spectrum at any distance from the sun for a given level of solar cycle modulation. Since August 1997 the Advanced Composition Explorer (ACE) stationed at the Earth-Sun L1 libration point (about 1.5 million km from earth) has provided GCR energy spectra for boron - nickel. The Cosmic Ray Isotope Spectrometer (CRIS) provides ``quiet time'' spectra in the range of highest modulation ˜ 50 -- 500 MeV / nucleon. The collection power of CRIS is much larger than any of the previous satellite or balloon GCR instruments: 250 cm**2 --sr compared to <10 cm**2-sr! This new data was used to update the original Badhwar -- O'Neill Model and greatly improve the interplanetary GCR prediction accuracy. When the new -- highly precise ACE CRIS data was analyzed it became obvious that the LIS spectrum for each element precisely fit a very simple analytical energy power-law that was suggested by Leonard Fisk over 30 years ago. The updated Badhwar -- O'Neill Model is shown to be accurate to within 5%, for elements such as oxygen, which have sufficient abundance that over 1000 ions are captured in each energy bin within a 30 day period. The paper clearly demonstrates the statistical relationship between the number of ions captured by the instrument in a given time and the precision of the model for each element. This is a significant model upgrade that should provide interplanetary mission planners with highly accurate GCR environment data for radiation protection for astronauts and radiation hardness assurance for electronic equipment.

Stopping powers and cross sections due to two-photon processes in relativistic nucleus-nucleus collision

NASA Technical Reports Server (NTRS)

Cheung, Wang K.; Norbury, John W.

1992-01-01

The radiation dose received from high energy galactic cosmic rays (GCR) is a limiting factor in the design of long duration space flights and the building of lunar and martian habitats. It is of vital importance to have an accurate understanding of the interactions of GCR in order to assess the radiation environment that the astronauts will be exposed to. Although previous studies have concentrated on the strong interaction process in GCR, there are also very large effects due to electromagnetic (EM) interactions. In this report we describe our first efforts at understanding these EM production processes due to two-photon collisions. More specifically, we shall consider particle production processes in relativistic heavy ion collisions (RHICs) through two-photon exchange.

Pattern formation in early embryogenesis of Xenopus laevis

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

Mglinets, V.A.

1995-07-01

Establishment of egg polarity, separation of germ layers, and the appearance of animal-vegetal, dorsoventral, and anteroposterior axes in Xenopus laevis embryos are considered. The control of these processes by gene coding for growth factors, protooncogens, and homeobox-containing genes is also been reviewed.

Corotating solar wind structures and recurrent trains of enhanced diurnal variation in galactic cosmic rays

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

Yeeram, T.; Ruffolo, D.; Sáiz, A.

Data from the Princess Sirindhorn Neutron Monitor at Doi Inthanon, Thailand, with a vertical cutoff rigidity of 16.8 GV, were utilized to determine the diurnal anisotropy (DA) of Galactic cosmic rays (GCRs) near Earth during solar minimum conditions between 2007 November and 2010 November. We identified trains of enhanced DA over several days, which often recur after a solar rotation period (∼27 days). By investigating solar coronal holes as identified from synoptic maps and solar wind parameters, we found that the intensity and anisotropy of cosmic rays are associated with the high-speed streams (HSSs) in the solar wind, which aremore » in turn related to the structure and evolution of coronal holes. An enhanced DA was observed after the onset of some, but not all, HSSs. During time periods of recurrent trains, the DA was often enhanced or suppressed according to the sign of the interplanetary magnetic field B, which suggests a contribution from a mechanism involving a southward gradient in the GCR density, n, and a gradient anisotropy along B × ∇n. In one non-recurrent and one recurrent sequence, an HSS from an equatorial coronal hole was merged with that from a trailing mid-latitude extension of a polar coronal hole, and the slanted HSS structure in space with suppressed GCR density can account for the southward GCR gradient. We conclude that the gradient anisotropy is a source of temporary changes in the GCR DA under solar minimum conditions, and that the latitudinal GCR gradient can sometimes be explained by the coronal hole morphology.« less

Guiding Preservice Teachers to Critically Reflect: Towards a Renewed Sense about English Learners

ERIC Educational Resources Information Center

Markos, Amy Michele

2011-01-01

The purpose of this practitioner inquiry was to explore the use of Guided Critical Reflection (GCR) in preparing preservice teachers for English learners (ELs). As a teacher researcher, I documented, analyzed, and discussed the ways in which students in my course used the process of GCR to transform their passively held understandings about ELs.…

How safe is safe enough? Radiation risk for a human mission to Mars.

PubMed

Cucinotta, Francis A; Kim, Myung-Hee Y; Chappell, Lori J; Huff, Janice L

2013-01-01

Astronauts on a mission to Mars would be exposed for up to 3 years to galactic cosmic rays (GCR)--made up of high-energy protons and high charge (Z) and energy (E) (HZE) nuclei. GCR exposure rate increases about three times as spacecraft venture out of Earth orbit into deep space where protection of the Earth's magnetosphere and solid body are lost. NASA's radiation standard limits astronaut exposures to a 3% risk of exposure induced death (REID) at the upper 95% confidence interval (CI) of the risk estimate. Fatal cancer risk has been considered the dominant risk for GCR, however recent epidemiological analysis of radiation risks for circulatory diseases allow for predictions of REID for circulatory diseases to be included with cancer risk predictions for space missions. Using NASA's models of risks and uncertainties, we predicted that central estimates for radiation induced mortality and morbidity could exceed 5% and 10% with upper 95% CI near 10% and 20%, respectively for a Mars mission. Additional risks to the central nervous system (CNS) and qualitative differences in the biological effects of GCR compared to terrestrial radiation may significantly increase these estimates, and will require new knowledge to evaluate.

Opening a Window on ICME-driven GCR Modulation in the Inner Solar System

NASA Astrophysics Data System (ADS)

Winslow, Reka M.; Schwadron, Nathan A.; Lugaz, Noé; Guo, Jingnan; Joyce, Colin J.; Jordan, Andrew P.; Wilson, Jody K.; Spence, Harlan E.; Lawrence, David J.; Wimmer-Schweingruber, Robert F.; Mays, M. Leila

2018-04-01

Interplanetary coronal mass ejections (ICMEs) often cause Forbush decreases (Fds) in the flux of galactic cosmic rays (GCRs). We investigate how a single ICME, launched from the Sun on 2014 February 12, affected GCR fluxes at Mercury, Earth, and Mars. We use GCR observations from MESSENGER at Mercury, ACE/LRO at the Earth/Moon, and MSL at Mars. We find that Fds are steeper and deeper closer to the Sun, and that the magnitude of the magnetic field in the ICME magnetic ejecta as well as the “strength” of the ICME sheath both play a large role in modulating the depth of the Fd. Based on our results, we hypothesize that (1) the Fd size decreases exponentially with heliocentric distance, and (2) that two-step Fds are more common closer to the Sun. Both hypotheses will be directly verifiable by the upcoming Parker Solar Probe and Solar Orbiter missions. This investigation provides the first systematic study of the changes in GCR modulation as a function of distance from the Sun using nearly contemporaneous observations at Mercury, Earth/Moon, and Mars, which will be critical for validating our physical understanding of the modulation process throughout the heliosphere.

How Safe Is Safe Enough? Radiation Risk for a Human Mission to Mars

PubMed Central

Cucinotta, Francis A.; Kim, Myung-Hee Y.; Chappell, Lori J.; Huff, Janice L.

2013-01-01

Astronauts on a mission to Mars would be exposed for up to 3 years to galactic cosmic rays (GCR) — made up of high-energy protons and high charge (Z) and energy (E) (HZE) nuclei. GCR exposure rate increases about three times as spacecraft venture out of Earth orbit into deep space where protection of the Earth's magnetosphere and solid body are lost. NASA's radiation standard limits astronaut exposures to a 3% risk of exposure induced death (REID) at the upper 95% confidence interval (CI) of the risk estimate. Fatal cancer risk has been considered the dominant risk for GCR, however recent epidemiological analysis of radiation risks for circulatory diseases allow for predictions of REID for circulatory diseases to be included with cancer risk predictions for space missions. Using NASA's models of risks and uncertainties, we predicted that central estimates for radiation induced mortality and morbidity could exceed 5% and 10% with upper 95% CI near 10% and 20%, respectively for a Mars mission. Additional risks to the central nervous system (CNS) and qualitative differences in the biological effects of GCR compared to terrestrial radiation may significantly increase these estimates, and will require new knowledge to evaluate. PMID:24146746

Characteristics and Energy Dependence of Recurrent Galactic Cosmic-Ray Flux Depressions and of a Forbush Decrease with LISA Pathfinder

NASA Astrophysics Data System (ADS)

Armano, M.; Audley, H.; Baird, J.; Bassan, M.; Benella, S.; Binetruy, P.; Born, M.; Bortoluzzi, D.; Cavalleri, A.; Cesarini, A.; Cruise, A. M.; Danzmann, K.; de Deus Silva, M.; Diepholz, I.; Dixon, G.; Dolesi, R.; Fabi, M.; Ferraioli, L.; Ferroni, V.; Finetti, N.; Fitzsimons, E. D.; Freschi, M.; Gesa, L.; Gibert, F.; Giardini, D.; Giusteri, R.; Grimani, C.; Grzymisch, J.; Harrison, I.; Heinzel, G.; Hewitson, M.; Hollington, D.; Hoyland, D.; Hueller, M.; Inchauspé, H.; Jennrich, O.; Jetzer, P.; Karnesis, N.; Kaune, B.; Korsakova, N.; Killow, C. J.; Laurenza, M.; Lobo, J. A.; Lloro, I.; Liu, L.; López-Zaragoza, J. P.; Maarschalkerweerd, R.; Mance, D.; Martín, V.; Martin-Polo, L.; Martino, J.; Martin-Porqueras, F.; Mateos, I.; McNamara, P. W.; Mendes, J.; Mendes, L.; Nofrarias, M.; Paczkowski, S.; Perreur-Lloyd, M.; Petiteau, A.; Pivato, P.; Plagnol, E.; Ramos-Castro, J.; Reiche, J.; Robertson, D. I.; Rivas, F.; Russano, G.; Sabbatini, F.; Slutsky, J.; Sopuerta, C. F.; Sumner, T.; Telloni, D.; Texier, D.; Thorpe, J. I.; Vetrugno, D.; Vitale, S.; Wanner, G.; Ward, H.; Wass, P.; Weber, W. J.; Wissel, L.; Wittchen, A.; Zambotti, A.; Zenoni, C.; Zweifel, P.

2018-02-01

Galactic cosmic-ray (GCR) energy spectra observed in the inner heliosphere are modulated by the solar activity, the solar polarity and structures of solar and interplanetary origin. A high counting rate particle detector (PD) aboard LISA Pathfinder, meant for subsystems diagnostics, was devoted to the measurement of GCR and solar energetic particle integral fluxes above 70 MeV n‑1 up to 6500 counts s‑1. PD data were gathered with a sampling time of 15 s. Characteristics and energy dependence of GCR flux recurrent depressions and of a Forbush decrease dated 2016 August 2 are reported here. The capability of interplanetary missions, carrying PDs for instrument performance purposes, in monitoring the passage of interplanetary coronal mass ejections is also discussed.

Neutron Environment Calculations for Low Earth Orbit

NASA Technical Reports Server (NTRS)

Clowdsley, M. S.; Wilson, J. W.; Shinn, J. L.; Badavi, F. F.; Heinbockel, J. H.; Atwell, W.

2001-01-01

The long term exposure of astronauts on the developing International Space Station (ISS) requires an accurate knowledge of the internal exposure environment for human risk assessment and other onboard processes. The natural environment is moderated by the solar wind, which varies over the solar cycle. The HZETRN high charge and energy transport code developed at NASA Langley Research Center can be used to evaluate the neutron environment on ISS. A time dependent model for the ambient environment in low earth orbit is used. This model includes GCR radiation moderated by the Earth's magnetic field, trapped protons, and a recently completed model of the albedo neutron environment formed through the interaction of galactic cosmic rays with the Earth's atmosphere. Using this code, the neutron environments for space shuttle missions were calculated and comparisons were made to measurements by the Johnson Space Center with onboard detectors. The models discussed herein are being developed to evaluate the natural and induced environment data for the Intelligence Synthesis Environment Project and eventual use in spacecraft optimization.

Ultra high molecular weight polyethylene (UHMWPE) fiber epoxy composite hybridized with Gadolinium and Boron nanoparticles for radiation shielding

NASA Astrophysics Data System (ADS)

Mani, Venkat; Prasad, Narasimha S.; Kelkar, Ajit

2016-09-01

Deep space radiations pose a major threat to the astronauts and their spacecraft during long duration space exploration missions. The two sources of radiation that are of concern are the galactic cosmic radiation (GCR) and the short lived secondary neutron radiations that are generated as a result of fragmentation that occurs when GCR strikes target nuclei in a spacecraft. Energy loss, during the interaction of GCR and the shielding material, increases with the charge to mass ratio of the shielding material. Hydrogen with no neutron in its nucleus has the highest charge to mass ratio and is the element which is the most effective shield against GCR. Some of the polymers because of their higher hydrogen content also serve as radiation shield materials. Ultra High Molecular Weight Polyethylene (UHMWPE) fibers, apart from possessing radiation shielding properties by the virtue of the high hydrogen content, are known for extraordinary properties. An effective radiation shielding material is the one that will offer protection from GCR and impede the secondary neutron radiations resulting from the fragmentation process. Neutrons, which result from fragmentation, do not respond to the Coulombic interaction that shield against GCR. To prevent the deleterious effects of secondary neutrons, targets such as Gadolinium are required. In this paper, the radiation shielding studies that were carried out on the fabricated sandwich panels by vacuum-assisted resin transfer molding (VARTM) process are presented. VARTM is a manufacturing process used for making large composite structures by infusing resin into base materials formed with woven fabric or fiber using vacuum pressure. Using the VARTM process, the hybridization of Epoxy/UHMWPE composites with Gadolinium nanoparticles, Boron, and Boron carbide nanoparticles in the form of sandwich panels were successfully carried out. The preliminary results from neutron radiation tests show that greater than 99% shielding performance was achieved with these sandwich panels. Moreover, the mechanical testing and thermo-physical analysis performed show that core materials can preserve their thermo-physical and mechanical integrity after radiation.

Evaluation of Mechanical Properties of Glass Fiber Posts Subjected to Laser Surface Treatments.

PubMed

Barbosa Siqueira, Carolina; Spadini de Faria, Natália; Raucci-Neto, Walter; Colucci, Vivian; Alves Gomes, Erica

2016-10-01

The aim of this study was to evaluate the influence of laser irradiation on flexural strength, elastic modulus, and surface roughness and morphology of glass fiber posts (GFPs). Laser treatment of GFPs has been introduced to improve its adhesion properties. A total of 40 GFPs were divided into 4 groups according to the irradiation protocol: GC-no irradiation, GYAG-irradiation with erbium:yttrium-aluminum-garnet [Er:YAG], GCR-irradiation with erbium, chromium:yttrium-scandium-gallium-garnet (Er,Cr:YSGG), and GDI-irradiation with diode laser. The GFP roughness and morphology were evaluated through laser confocal microscopy before and after surface treatment. Three-point bending flexural test measured flexural strength and elastic modulus. Data about elastic modulus and flexural strength were subjected to one-way ANOVA and Bonferroni test (p < 0.05). The effect of roughness was evaluated using the linear mixed effects model and Bonferroni test (p < 0.05). Laser treatment changed surface roughness in the groups GCR (p = 0.000) and GDI (p = 0.007). The mean flexural strength in GYAG (995.22 MPa) was similar to that in GC (980.48 MPa) (p = 1.000) but different from that in GCR (746.83 MPa) and that in GDI (691.34 MPa) (p = 0.000). No difference was found between the groups GCR and GDI (p = 0.86). For elastic modulus: GYAG (24.47 GPa) was similar to GC (25.92 GPa) (p = 1.000) but different from GCR (19.88 GPa) (p = 0.002) and GDI (17.20 GPa) (p = 0.000). The different types of lasers, especially Er,Cr:YSGG and 980 ηm diode, influenced the mechanical properties of GFPs.

AVERAGE SPATIAL DISTRIBUTION OF COSMIC RAYS BEHIND THE INTERPLANETARY SHOCK—GLOBAL MUON DETECTOR NETWORK OBSERVATIONS

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

Kozai, M.; Munakata, K.; Kato, C.

2016-07-10

We analyze the galactic cosmic ray (GCR) density and its spatial gradient in Forbush Decreases (FDs) observed with the Global Muon Detector Network (GMDN) and neutron monitors (NMs). By superposing the GCR density and density gradient observed in FDs following 45 interplanetary shocks (IP-shocks), each associated with an identified eruption on the Sun, we infer the average spatial distribution of GCRs behind IP-shocks. We find two distinct modulations of GCR density in FDs, one in the magnetic sheath and the other in the coronal mass ejection (CME) behind the sheath. The density modulation in the sheath is dominant in themore » western flank of the shock, while the modulation in the CME ejecta stands out in the eastern flank. This east–west asymmetry is more prominent in GMDN data responding to ∼60 GV GCRs than in NM data responding to ∼10 GV GCRs, because of the softer rigidity spectrum of the modulation in the CME ejecta than in the sheath. The geocentric solar ecliptic- y component of the density gradient, G {sub y}, shows a negative (positive) enhancement in FDs caused by the eastern (western) eruptions, while G {sub z} shows a negative (positive) enhancement in FDs caused by the northern (southern) eruptions. This implies that the GCR density minimum is located behind the central flank of IP-shocks and propagating radially outward from the location of the solar eruption. We also confirmed that the average G {sub z} changes its sign above and below the heliospheric current sheet, in accord with the prediction of the drift model for the large-scale GCR transport in the heliosphere.« less

A Reference Field for GCR Simulation and an LET-Based Implementation at NSRL

NASA Technical Reports Server (NTRS)

Slaba, Tony C.; Blattnig, Steve R.; Walker, Steven A.; Norbury, John W.

2015-01-01

Exposure to galactic cosmic rays (GCR) on long duration deep space missions presents a serious health risk to astronauts, with large uncertainties connected to the biological response. In order to reduce the uncertainties and gain understanding about the basic mechanisms through which space radiation initiates cancer and other endpoints, radiobiology experiments are performed. Some of the accelerator facilities supporting such experiments have matured to a point where simulating the broad range of particles and energies characteristic of the GCR environment in a single experiment is feasible from a technology, usage, and cost perspective. In this work, several aspects of simulating the GCR environment in the laboratory are discussed. First, comparisons are made between direct simulation of the external, free space GCR field and simulation of the induced tissue field behind shielding. It is found that upper energy constraints at the NASA Space Radiation Laboratory (NSRL) limit the ability to simulate the external, free space field directly (i.e. shielding placed in the beam line in front of a biological target and exposed to a free space spectrum). Second, variation in the induced tissue field associated with shielding configuration and solar activity is addressed. It is found that the observed variation is within physical uncertainties, allowing a single reference field for deep space missions to be defined. Third, an approach for simulating the reference field at NSRL is presented. The approach allows for the linear energy transfer (LET) spectrum of the reference field to be approximately represented with discrete ion and energy beams and implicitly maintains a reasonably accurate charge spectrum (or, average quality factor). Drawbacks of the proposed methodology are discussed and weighed against alternative simulation strategies. The neutron component and track structure characteristics of the proposed strategy are discussed in this context.

Criteria for confirming sequence periodicity identified by Fourier transform analysis: application to GCR2, a candidate plant GPCR?

PubMed

Illingworth, Christopher J R; Parkes, Kevin E; Snell, Christopher R; Mullineaux, Philip M; Reynolds, Christopher A

2008-03-01

Methods to determine periodicity in protein sequences are useful for inferring function. Fourier transformation is one approach but care is required to ensure the periodicity is genuine. Here we have shown that empirically-derived statistical tables can be used as a measure of significance. Genuine protein sequences data rather than randomly generated sequences were used as the statistical backdrop. The method has been applied to G-protein coupled receptor (GPCR) sequences, by Fourier transformation of hydrophobicity values, codon frequencies and the extent of over-representation of codon pairs; the latter being related to translational step times. Genuine periodicity was observed in the hydrophobicity whereas the apparent periodicity (as inferred from previously reported measures) in the translation step times was not validated statistically. GCR2 has recently been proposed as the plant GPCR receptor for the hormone abscisic acid. It has homology to the Lanthionine synthetase C-like family of proteins, an observation confirmed by fold recognition. Application of the Fourier transform algorithm to the GCR2 family revealed strongly predicted seven fold periodicity in hydrophobicity, suggesting why GCR2 has been reported to be a GPCR, despite negative indications in most transmembrane prediction algorithms. The underlying multiple sequence alignment, also required for the Fourier transform analysis of periodicity, indicated that the hydrophobic regions around the 7 GXXG motifs commence near the C-terminal end of each of the 7 inner helices of the alpha-toroid and continue to the N-terminal region of the helix. The results clearly explain why GCR2 has been understandably but erroneously predicted to be a GPCR.

Interpreting high time resolution galactic cosmic ray observations in a diffusive context

NASA Astrophysics Data System (ADS)

Jordan, A.; Spence, H. E.; Blake, J. B.; Shaul, D. A.

2009-12-01

We interpret galactic cosmic ray (GCR) variations near Earth within a diffusive context. The variations occur on time-/size-scales ranging from Forbush decreases (Fds), to substructure embedded within Fds, to smaller amplitude and shorter duration variations during relatively benign interplanetary conditions. We use high time resolution GCR observations from the High Sensitivity Telescope (HIST) on Polar and from the Spectrometer for INTEGRAL (SPI) and also use solar wind plasma and magnetic field observations from ACE and/or Wind. To calculate the coefficient of diffusion, we combine these datasets with a simple convection-diffusion model for relativistic charged particles in a magnetic field. We find reasonable agreement between our and previous estimates of the coefficient. We also show whether changes in the coefficient of diffusion are sufficient to explain the above GCR variations.

Simulation of Earth-Moon-Mars Environments for the Assessment of Organ Doses

NASA Astrophysics Data System (ADS)

Kim, M. Y.; Schwadron, N. A.; Townsend, L.; Cucinotta, F. A.

2010-12-01

Space radiation environments for historically large solar particle events (SPE) and galactic cosmic rays (GCR) at solar minimum and solar maximum are simulated in order to characterize exposures to radio-sensitive organs for missions to low-Earth orbit (LEO), moon, and Mars. Primary and secondary particles for SPE and GCR are transported through the respective atmosphere of Earth or Mars, space vehicle, and astronaut’s body tissues using the HZETRN/QMSFRG computer code. In LEO, exposures are reduced compared to deep space because particles are deflected by the Earth’s magnetic field and absorbed by the solid body of the Earth. Geomagnetic transmission function as a function of altitude was applied for the particle flux of charged particles, and the shift of the organ exposures to higher velocity or lower stopping powers compared to those in deep space was analyzed. In the transport through Mars atmosphere, a vertical distribution of atmospheric thickness was calculated from the temperature and pressure data of Mars Global Surveyor, and the directional cosine distribution was implemented to describe the spherically distributed atmospheric distance along the slant path at each altitude. The resultant directional shielding by Mars atmosphere at solar minimum and solar maximum was used for the particle flux simulation at various altitudes on the Martian surface. Finally, atmospheric shielding was coupled with vehicle and body shielding for organ dose estimates. We made predictions of radiation dose equivalents and evaluated acute symptoms at LEO, moon, and Mars at solar minimum and solar maximum.

Comparisons Between Model Predictions and Spectral Measurements of Charged and Neutral Particles on the Martian Surface

NASA Technical Reports Server (NTRS)

Kim, Myung-Hee Y.; Cucinotta, Francis A.; Zeitlin, Cary; Hassler, Donald M.; Ehresmann, Bent; Rafkin, Scot C. R.; Wimmer-Schweingruber, Robert F.; Boettcher, Stephan; Boehm, Eckart; Guo, Jingnan;

The PHITS code for space applications: status and recent developments

NASA Astrophysics Data System (ADS)

Sihver, Lembit; Ploc, Ondrej; Sato, Tatsuhiko; Niita, Koji; Hashimoto, Shintaro; El-Jaby, Samy

Since COSPAR 2012, the Particle and Heavy Ion Transport code System, PHITS, has been upgraded and released to the public [1]. The code has been improved and so has the contents of its package, such as the attached data libraries. In the new version, the intra-nuclear cascade models INCL4.6 and INC-ELF have been implemented as well as the Kurotama model for the total reaction cross sections. The accuracies of the new reaction models for transporting the galactic cosmic-rays were investigated by comparing with experimental data. The incorporation of these models has improved the capabilities of PHITS to perform particle transport simulations for different space applications. A methodology for assessing the pre-mission exposure of space crew aboard the ISS has been developed in terms of an effective dose equivalent [2]. PHITS was used to calculate the particle transport of the GCR and trapped radiation through the hull of the ISS. By using the predicted spectra, and fluence-to-dose conversion factors, the semi-empirical ISSCREM [3,4,5] code was then scaled to predict the effective dose equivalent. This methodology provides an opportunity for pre-flight predictions of the effective dose equivalent, which can be compared to post-flight estimates, and therefore offers a means to assess the impact of radiation exposure on ISS flight crew. We have also simulated [6] the protective curtain experiment, which was performed to test the efficiency of water-soaked hygienic tissue wipes and towels as a simple and cost-effective additional spacecraft shielding. The dose from the trapped particles and low energetic GCR, was significantly reduced, which shows that the protective curtains are efficient when they are applied on spacecraft at LEO. The results of these benchmark calculations, as well as the mentioned applications of PHITS to space dosimetry, will be presented. [1] T. Sato et al. J. Nucl. Sci. Technol. 50, 913-923 (2013). [2] S. El-Jaby, et al. Adv. Space Res. doi: http://dx.doi.org/10.1016/j.asr.2013.12.022 (2013). [3] S. El-Jaby, et al. Adv. Space Res. doi: http://dx.doi.org/10.1016/j.asr.2013.10.006 (2013). [4] S. El-Jaby, et al. In proc. to the IEEE Aerospace Conference, Big Sky, MN, USA (2013). [5] S. El-Jaby, PhD Thesis, Royal Military College of Canada (2012). [6] O. Ploc, et al., Adv. Space Res. 52, 1911-1918 (2013).

Managing Lunar and Mars Mission Radiation Risks. Part 1; Cancer Risks, Uncertainties, and Shielding Effectiveness

NASA Technical Reports Server (NTRS)

Cucinotta, Francis A.; Kim, Myung-Hee Y.; Ren, Lei

2005-01-01

This document addresses calculations of probability distribution functions (PDFs) representing uncertainties in projecting fatal cancer risk from galactic cosmic rays (GCR) and solar particle events (SPEs). PDFs are used to test the effectiveness of potential radiation shielding approaches. Monte-Carlo techniques are used to propagate uncertainties in risk coefficients determined from epidemiology data, dose and dose-rate reduction factors, quality factors, and physics models of radiation environments. Competing mortality risks and functional correlations in radiation quality factor uncertainties are treated in the calculations. The cancer risk uncertainty is about four-fold for lunar and Mars mission risk projections. For short-stay lunar missins (<180 d), SPEs present the most significant risk, but one effectively mitigated by shielding. For long-duration (>180 d) lunar or Mars missions, GCR risks may exceed radiation risk limits. While shielding materials are marginally effective in reducing GCR cancer risks because of the penetrating nature of GCR and secondary radiation produced in tissue by relativisitc particles, polyethylene or carbon composite shielding cannot be shown to significantly reduce risk compared to aluminum shielding. Therefore, improving our knowledge of space radiobiology to narrow uncertainties that lead to wide PDFs is the best approach to ensure radiation protection goals are met for space exploration.

SU-D-BRD-03: A Gateway for GPU Computing in Cancer Radiotherapy Research

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

Jia, X; Folkerts, M; Shi, F

Purpose: Graphics Processing Unit (GPU) has become increasingly important in radiotherapy. However, it is still difficult for general clinical researchers to access GPU codes developed by other researchers, and for developers to objectively benchmark their codes. Moreover, it is quite often to see repeated efforts spent on developing low-quality GPU codes. The goal of this project is to establish an infrastructure for testing GPU codes, cross comparing them, and facilitating code distributions in radiotherapy community. Methods: We developed a system called Gateway for GPU Computing in Cancer Radiotherapy Research (GCR2). A number of GPU codes developed by our group andmore » other developers can be accessed via a web interface. To use the services, researchers first upload their test data or use the standard data provided by our system. Then they can select the GPU device on which the code will be executed. Our system offers all mainstream GPU hardware for code benchmarking purpose. After the code running is complete, the system automatically summarizes and displays the computing results. We also released a SDK to allow the developers to build their own algorithm implementation and submit their binary codes to the system. The submitted code is then systematically benchmarked using a variety of GPU hardware and representative data provided by our system. The developers can also compare their codes with others and generate benchmarking reports. Results: It is found that the developed system is fully functioning. Through a user-friendly web interface, researchers are able to test various GPU codes. Developers also benefit from this platform by comprehensively benchmarking their codes on various GPU platforms and representative clinical data sets. Conclusion: We have developed an open platform allowing the clinical researchers and developers to access the GPUs and GPU codes. This development will facilitate the utilization of GPU in radiation therapy field.« less

Influence of Sun and Other Cosmic Factors on Environment of the Earth

DTIC Science & Technology

2010-01-07

of the secondary cosmic rays (mostly muons , electrons, neutrons and gammas) can provide highly cost-effective information on the key characteristics...Coronal mass ejection (CME) from the Sun the impact on the Galactic Cosmic rays (GCR) will be observed. Particle detector is vital for measuring the...modulation effects the sun poses on the ambient population of the Galactic Cosmic Rays (GCR). The known agents of these modulation effects are Solar Flares

The Development of Materials for Structures and Radiation Shielding in Aerospace

NASA Technical Reports Server (NTRS)

Kiefer, Richard L.; Orwoll, Robert A.

2001-01-01

Polymeric materials on space vehicles and high-altitude aircraft win be exposed to highly penetrating radiations. These radiations come from solar flares and galactic cosmic rays (GCR). Radiation from solar flares consists primarily of protons with energies less than 1 GeV. On the other hand, GCR consist of nuclei with energies as high as 10(exp 10) GeV. Over 90% of the nuclei in GCR are protons and alpha particles, however there is a small but significant component of particles with atomic numbers greater than ten. Particles with high atomic number (Z) and high energy interact with very high specific ionization and thus represent a serious hazard for humans and electronic equipment on a spacecraft or on high-altitude commercial aircraft (most importantly for crew members who would have long exposures). Neutrons generated by reactions with the high energy particles also represent a hazard both for humans and electronic equipment.

Evaluation of SPE and GCR Radiation Effects in Inflatable, Space Suit and Composite Habitat Materials Project

NASA Technical Reports Server (NTRS)

Waller, Jess M.; Nichols, Charles

2016-01-01

The radiation resistance of polymeric and composite materials to space radiation is currently based on irradiating materials with Co-60 gamma-radiation to the equivalent total ionizing dose (TID) expected during mission. This is an approximation since gamma-radiation is not truly representative of the particle species; namely, Solar Particle Event (SPE) protons and Galactic Cosmic Ray (GCR) nucleons, encountered in space. In general, the SPE and GCR particle energies are much higher than Co-60 gamma-ray photons, and since the particles have mass, there is a displacement effect due to nuclear collisions between the particle species and the target material. This effort specifically bridges the gap between estimated service lifetimes based on decades old Co-60 gamma-radiation data, and newer assessments of what the service lifetimes actually are based on irradiation with particle species that are more representative of the space radiation environment.

Influence of Secondary Cooling Mode on Solidification Structure and Macro-segregation Behavior for High-carbon Continuous Casting Bloom

NASA Astrophysics Data System (ADS)

Dou, Kun; Yang, Zhenguo; Liu, Qing; Huang, Yunhua; Dong, Hongbiao

2017-07-01

A cellular automaton-finite element coupling model for high-carbon continuously cast bloom of GCr15 steel is established to simulate the solidification structure and to investigate the influence of different secondary cooling modes on characteristic parameters such as equiaxed crystal ratio, grain size and secondary dendrite arm spacing, in which the effect of phase transformation and electromagnetic stirring is taken into consideration. On this basis, evolution of carbon macro-segregation for GCr15 steel bloom is researched correspondingly via industrial tests. Based on above analysis, the relationship among secondary cooling modes, characteristic parameters for solidification structure as well as carbon macro-segregation is illustrated to obtain optimum secondary cooling strategy and alleviate carbon macro-segregation degree for GCr15 steel bloom in continuous casting process. The evaluating method for element macro-segregation is applicable in various steel types.

Modulation of UK lightning by heliospheric magnetic field polarity

NASA Astrophysics Data System (ADS)

Owens, M. J.; Scott, C. J.; Lockwood, M.; Barnard, L.; Harrison, R. G.; Nicoll, K.; Watt, C.; Bennett, A. J.

2014-11-01

Observational studies have reported solar magnetic modulation of terrestrial lightning on a range of time scales, from days to decades. The proposed mechanism is two-step: lightning rates vary with galactic cosmic ray (GCR) flux incident on Earth, either via changes in atmospheric conductivity and/or direct triggering of lightning. GCR flux is, in turn, primarily controlled by the heliospheric magnetic field (HMF) intensity. Consequently, global changes in lightning rates are expected. This study instead considers HMF polarity, which doesn't greatly affect total GCR flux. Opposing HMF polarities are, however, associated with a 40-60% difference in observed UK lightning and thunder rates. As HMF polarity skews the terrestrial magnetosphere from its nominal position, this perturbs local ionospheric potential at high latitudes and local exposure to energetic charged particles from the magnetosphere. We speculate as to the mechanism(s) by which this may, in turn, redistribute the global location and/or intensity of thunderstorm activity.

A model of galactic cosmic rays for use in calculating linear energy transfer spectra

NASA Technical Reports Server (NTRS)

Chen, J.; Chenette, D.; Clark, R.; Garcia-Munoz, M.; Guzik, T. G.; Pyle, K. R.; Sang, Y.; Wefel, J. P.

1994-01-01

The Galactic Cosmic Rays (GCR) contain fully stripped nuclei, from Hydrogen to beyond the Iron group, accelerated to high energies and are a major component of the background radiation encountered by satellites and interplanetary spacecraft. This paper presents a GCR model which is based upon our current understanding of the astrophysics of GCR transport through interstellar and interplanetary space. The model can be used to predict the energy spectra for all stable and long-lived radioactive species from H to Ni over an energy range from 50 to 50,000 MeV/nucleon as a function of a single parameter, the solar modulation level phi. The details of this model are summarized, phi is derived for the period 1974 to present, and results from this model during the 1990/1991 Combined Release and Radiation Effects Satellite (CRRES) mission are presented.

Opening a Window on ICME Evolution and GCR Modulation During Propagation in the Innermost Heliosphere

NASA Astrophysics Data System (ADS)

Winslow, R. M.; Lugaz, N.; Schwadron, N.; Farrugia, C. J.; Guo, J.; Wimmer-Schweingruber, R. F.; Wilson, J. K.; Joyce, C.; Jordan, A.; Lawrence, D. J.

2017-12-01

We use multipoint spacecraft observations to study interplanetary coronal mass ejection (ICME) evolution and subsequent galactic cosmic ray (GCR) modulation during propagation in the inner heliosphere. We illustrate ICME propagation effects through two different case studies. The first ICME was launched from the Sun on 29 December 2011 and was observed in near-perfect longitudinal conjunction at MESSENGER and STEREO A. Despite the close longitudinal alignment, we infer from force-free field modeling that the orientation of the underlying flux rope rotated ˜80o in latitude and ˜65o in longitude. Based on both spacecraft measurements as well as ENLIL model simulations of the steady state solar wind, we find that interactions involving magnetic reconnection with corotating structures in the solar wind dramatically alter the ICME magnetic field. In particular, we observed at STEREO A a highly turbulent region with distinct properties within the flux rope that was not observed at MESSENGER; we attribute this region to interaction between the ICME and a heliospheric plasma sheet/current sheet. This is a concrete example of a sequence of events that can increase the complexity of ICMEs during propagation and should serve as a caution on using very distant observations to predict the geoeffectiveness of large interplanetary transients. Our second case study investigates changes with heliospheric distance in GCR modulation by an ICME event (launched on 12 February 2014) observed in near-conjunction at all four of the inner solar system planets. The ICME caused Forbush decreases (FDs) in the GCR count rates at Mercury (MESSENGER), Earth/Moon (ACE/LRO), and Mars (MSL). At all three locations, the pre-ICME background GCR rate was well-matched, but the depth of the FD of GCR fluxes with similar energy ranges diminished with distance from the Sun. A larger difference in FD size was observed between Mercury and Earth than between Earth and Mars, partly owing to the much larger drop in the ICME magnetic field magnitude between Mercury and Earth, and to the faster ICME speed decrease closer to the Sun. The results from these case studies give both a direct and indirect view of how ICMEs evolve during propagation as well as a glimpse of the inner heliosphere environment about to be explored by the Parker Solar Probe and Solar Orbiter.

Global forecast of antimicrobial resistance in invasive isolates of Escherichia coli and Klebsiella pneumoniae.

PubMed

Alvarez-Uria, Gerardo; Gandra, Sumanth; Mandal, Siddhartha; Laxminarayan, Ramanan

2018-03-01

To project future antimicrobial resistance (AMR) in Escherichia coli and Klebsiella pneumoniae. Mixed linear models were constructed from a sample of countries with AMR data in the ResistanceMap database. Inverse probability weighting methods were used to account for countries without AMR data. The estimated prevalence of AMR in 2015 was 64.5% (95% confidence interval (CI) 42-87%) for third-generation cephalosporin-resistant (3GCR) Escherichia coli, 5.8% (95% CI 1.8-9.7%) for carbapenem-resistant (CR) E. coli, 66.9% (95% CI 47.1-86.8%) for 3GCR Klebsiella pneumoniae, and 23.4% (95% CI 7.4-39.4%) for CR K. pneumoniae. The projected AMR prevalence in 2030 was 77% (95% CI 55-99.1%) for 3GCR E. coli, 11.8% (95% CI 3.7-19.9%) for CR E. coli, 58.2% (95% CI 50.2-66.1%) for 3GCR K. pneumoniae, and 52.8% (95% CI 16.3-89.3%) for CR K. pneumoniae. The models suggest that third-generation cephalosporins and carbapenems could be ineffective against a sizeable proportion of infections by E. coli and K. pneumoniae in most parts of the world by 2030, supporting both the need to enhance stewardship efforts and to prioritize research and development of new antibiotics for resistant Enterobacteriaceae. Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.

The Projection of Space Radiation Environments with a Solar Cycle Statistical Model

NASA Technical Reports Server (NTRS)

Kim, Myung-Hee; Cucinotta, Francis A.; Wilson, John W.

2006-01-01

A solar cycle statistical model has been developed to project sunspot numbers which represent the variations in the space radiation environment. The resultant projection of sunspot numbers in near future were coupled to space-related quantities of interest in radiation protection, such as the galactic cosmic radiation (GCR) deceleration potential (f) and the mean occurrence frequency of solar particle event (SPE). Future GCR fluxes have been derived from a predictive model, in which GCR temporal dependence represented by f was derived from GCR flux and ground-based Climax neutron monitor rate measurements over the last four decades. Results showed that the point dose equivalent inside a typical spacecraft in interplanetary radiation fields was influenced by solar modulation up to a factor of three. One important characteristic of sporadic SPEs is their mean frequency of occurrence, which is dependent on solar activity. Projections of future mean frequency of SPE occurrence were estimated from a power law function of sunspot number. Furthermore, the cumulative probabilities of SPE during short-period missions were defined with the continuous database of proton fluences of SPE. The analytic representation of energy spectra of SPE was constructed by the Weibull distribution for different event sizes. The representative exposure level at each event size was estimated for the guideline of protection systems for astronauts during future space exploration missions.

Determining the Magnitude of Neutron and Galactic Cosmic Ray (GCR) Fluxes at the Moon using the Lunar Exploration Neutron Detector during the Historic Space-Age Era of High GCR Flux

NASA Astrophysics Data System (ADS)

Chin, G.; Sagdeev, R.; Boynton, W. V.; Mitrofanov, I. G.; Milikh, G. M.; Su, J. J.; Livengood, T. A.; McClanahan, T. P.; Evans, L.; Starr, R. D.; litvak, M. L.; Sanin, A.

2013-12-01

The Lunar Reconnaissance Orbiter (LRO) was launched June 18, 2009 during an historic space-age era of minimum solar activity [1]. The lack of solar sunspot activity signaled a complex set of heliospheric phenomena [2,3,4] that also gave rise to a period of unprecedentedly high Galactic Cosmic Ray (GCR) flux [5]. These events coincided with the primary mission of the Lunar Exploration Neutron Detector (LEND, [6]), onboard LRO in a nominal 50-km circular orbit of the Moon [7]. Methods to calculate the emergent neutron albedo population using Monte Carlo techniques [8] rely on an estimate of the GCR flux and spectra calibrated at differing periods of solar activity [9,10,11]. Estimating the actual GCR flux at the Moon during the LEND's initial period of operation requires a correction using a model-dependent heliospheric transport modulation parameter [12] to adjust the GCR flux appropriate to this unique solar cycle. These corrections have inherent uncertainties depending on model details [13]. Precisely determining the absolute neutron and GCR fluxes is especially important in understanding the emergent lunar neutrons measured by LEND and subsequently in estimating the hydrogen/water content in the lunar regolith [6]. LEND is constructed with a set of neutron detectors to meet differing purposes [6]. Specifically there are two sets of detector systems that measure the flux of epithermal neutrons: a) the uncollimated Sensor for Epi-Thermal Neutrons (SETN) and b) the Collimated Sensor for Epi-Thermal Neutrons (CSETN). LEND SETN and CSETN observations form a complementary set of simultaneous measurements that determine the absolute scale of emergent lunar neutron flux in an unambiguous fashion and without the need for correcting to differing solar-cycle conditions. LEND measurements are combined with a detailed understanding of the sources of instrumental back-ground, and the performance of CSETN and SETN. This comparison allows us to calculate a constant scale factor that determines the absolute flux of neutrons at the Moon and then subsequently to deduce the proper scale of the GCR flux. References: [1] H. S. Ahluwakia and R. C. Ygbuhay (2010) Twelfth International Solar Wind Conference, 699-702. [2] F. B. McDonald et al. (2010) JRL, 37, L18101. [3] H. Moraal and P. H. Stoker (2010) JGR, 115, 12109-12118. [4] R. Kataoka et al. (2012) Space Weather, 10, 11001-11007. [4] C-L. Huang et al. (2009), JRL, 37, L09109-L09104. [5] R. A. Mewaldt et al. (2010) Ap. J Lett., 723, L1-L6. [6] I. G. Mitrofanov et al. (2010) Space Science Rev., 150, 283-207. [7] C. R. Tooley et al. (2010) Space Science Rev., 150, 23-62. [8] G. W. McKinney et al. (2006) JGR, 111, 6004-6018. [9] P. M. O'Neil (2010) IEEE Trans. Nucl. Sci., 57(6), 3148-3153. [10] American National Standards Institute Tech. Rep. ISO 15390 (2004). [11] I. G. Usokin et al. (2008) JGR, 110, A12108. [12] M. D. Looper et al. (2013) Space Weather, 11, 142-152. [13] A. I. Mrigakshi et al. (2012) JGR, 117, A08109-A08121.

Characterization of germ cell-specific expression of the orphan nuclear receptor, germ cell nuclear factor.

PubMed

Katz, D; Niederberger, C; Slaughter, G R; Cooney, A J

1997-10-01

Nuclear receptors, such as those for androgens, estrogens, and progesterones, control many reproductive processes. Proteins with structures similar to these receptors, but for which ligands have not yet been identified, have been termed orphan nuclear receptors. One of these orphans, germ cell nuclear factor (GCNF), has been shown to be germ cell specific in the adult and, therefore, may also participate in the regulation of reproductive functions. In this paper, we examine more closely the expression patterns of GCNF in germ cells to begin to define spatio-temporal domains of its activity. In situ hybridization showed that GCNF messenger RNA (mRNA) is lacking in the testis of hypogonadal mutant mice, which lack developed spermatids, but is present in the wild-type testis. Thus, GCNF is, indeed, germ cell specific in the adult male. Quantitation of the specific in situ hybridization signal in wild-type testis reveals that GCNF mRNA is most abundant in stage VII round spermatids. Similarly, Northern analysis and specific in situ hybridization show that GCNF expression first occurs in testis of 20-day-old mice, when round spermatids first emerge. Therefore, in the male, GCNF expression occurs postmeiotically and may participate in the morphological changes of the maturing spermatids. In contrast, female expression of GCNF is shown in growing oocytes that have not completed the first meiotic division. Thus, GCNF in the female is expressed before the completion of meiosis. Finally, the nature of the two different mRNAs that hybridize to the GCNF complementary DNA was studied. Although both messages contain the DNA binding domain, only the larger message is recognized by a probe from the extreme 3' untranslated region. In situ hybridization with these differential probes demonstrates that both messages are present in growing oocytes. In addition, the coding region and portions of the 3' untranslated region of the GCNF complementary DNA are conserved in the rat.

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

Guzik, T. G.; Clayton, E.; Wefel, J. P.

The space radiation environment for the CLEMENTINE I mission was investigated using a new calculational model, CHIME, which includes the effects of galactic cosmic rays (GCR), anomalous component (AC) species and solar energetic particle (SEP) events and their variations as a function of time. Unlike most previous radiation environment models, CHIME is based upon physical theory and is {open_quotes}calibrated{close_quotes} with energetic particle measurements made over the last two decades. Thus, CHIME provides an advance in the accuracy of estimating the interplanetary radiation environment. Using this model we have calculated particle energy spectra, fluences and linear energy transfer (LET) spectra formore » all three major components of the CLEMENTINE I mission during 1994: (1) the spacecraft in lunar orbit, (2) the spacecraft during asteroid flyby, and (3) the interstate adapter USA in Earth orbit. Our investigations indicate that during 1994 the level of solar modulation, which dominates the variation in the GCR and AC flux as a function of time, will be decreasing toward solar minimum levels. Consequently the GCR and AC flux will be increasing during Y, the year and, potentially, will rise to levels seen during previous solar minimums. The estimated radiation environment also indicates that the AC will dominate the energetic particle spectra for energies below 30-50 MeV/nucleon, while the GCR have a peak flux at {approximately}300 MeV/nucleon and maintain a relatively high flux level up to >1000 MeV/nucleon. The AC significantly enhances the integrated flux for LET in the range 1 to 10 MeV/(mg/cm{sup 2}), but due to the steep energy spectra of the AC a relatively small amount of material ({approximately}50 mils of Al) can effectively shield against this component. The GCR are seen to be highly penetrating and require massive amounts of shielding before there is any appreciable decrease in the LET flux.« less

Accurate quantification of 5 German cockroach (GCr) allergens in complex extracts using multiple reaction monitoring mass spectrometry (MRM MS).

PubMed

Mindaye, S T; Spiric, J; David, N A; Rabin, R L; Slater, J E

2017-12-01

German cockroach (GCr) allergen extracts are complex and heterogeneous products, and methods to better assess their potency and composition are needed for adequate studies of their safety and efficacy. The objective of this study was to develop an assay based on liquid chromatography and multiple reaction monitoring mass spectrometry (LC-MRM MS) for rapid, accurate, and reproducible quantification of 5 allergens (Bla g 1, Bla g 2, Bla g 3, Bla g 4, and Bla g 5) in crude GCr allergen extracts. We first established a comprehensive peptide library of allergens from various commercial extracts as well as recombinant allergens. Peptide mapping was performed using high-resolution MS, and the peptide library was then used to identify prototypic and quantotypic peptides to proceed with MRM method development. Assay development included a systematic optimization of digestion conditions (buffer, digestion time, and trypsin concentration), chromatographic separation, and MS parameters. Robustness and suitability were assessed following ICH (Q2 [R1]) guidelines. The method is precise (RSD < 10%), linear over a wide range (r > 0.99, 0.01-1384 fmol/μL), and sensitive (LLOD and LLOQ <1 fmol/μL). Having established the parameters for LC-MRM MS, we quantified allergens from various commercial GCr extracts and showed considerable variability that may impact clinical efficacy. Our data demonstrate that the LC-MRM MS method is valuable for absolute quantification of allergens in GCr extracts and likely has broader applicability to other complex allergen extracts. Definitive quantification provides a new standard for labelling of allergen extracts, which will inform patient care, enable personalized therapy, and enhance the efficacy of immunotherapy for environmental and food allergies. © 2017 The Authors. Clinical & Experimental Allergy published by John Wiley & Sons Ltd. This article has been contributed to by US Government employees and their work is in the public domain in the USA.

Steroid resistance in COPD is associated with impaired molecular chaperone Hsp90 expression by pro-inflammatory lymphocytes.

PubMed

Hodge, Greg; Roscioli, Eugene; Jersmann, Hubertus; Tran, Hai B; Holmes, Mark; Reynolds, Paul N; Hodge, Sandra

2016-10-21

Corticosteroid resistance is a major barrier to effective treatment of COPD. We have shown that the resistance is associated with decreased expression of glucocorticoid receptor (GCR) by senescent CD28nullCD8+ pro-inflammatory lymphocytes in peripheral blood of COPD patients. GCR must be bound to molecular chaperones heat shock proteins (Hsp) 70 and Hsp90 to acquire a high-affinity steroid binding conformation, and traffic to the nucleus. We hypothesized a loss of Hsp70/90 from these lymphocytes may further contribute to steroid resistance in COPD. Blood was collected from COPD (n = 10) and aged-matched controls (n = 10). To assess response to steroids, cytotoxic mediators, intracellular pro-inflammatory cytokines, CD28, GCR, Hsp70 and Hsp90 were determined in T and NKT-like cells in the presence of ± 10 μM prednisolone and 2.5 ng/mL cyclosporine A (binds to GCR-Hsp70/90 complex) using flow cytometry, western blot and fluorescence microscopy. A loss of expression of Hsp90 and GCR from CD28null CD8+ T and NKT-like cells in COPD was noted (Hsp70 unchanged). Loss of Hsp90 expression correlated with the percentage of CD28null CD8+ T and NKT-like cells producing IFNγ or TNFα in all subjects (eg, COPD: R = -0.763, p = 0.007 for T-cell IFNγ). Up-regulation of Hsp90 and associated decrease in pro-inflammatory cytokine production was found in CD28nullCD8+ T and NKT-like cells in the presence of 10 μM prednisolone and 2.5 ng/mL cyclosporine A. Loss of Hsp90 from cytotoxic/pro-inflammatory CD28nullCD8+ T and NKT-like cells could contribute to steroid resistance in COPD. Combination prednisolone and low-dose cyclosporine A therapy inhibits these pro-inflammatory cells and may reduce systemic inflammation in COPD.

Simulation and Comparison of Martian Surface Ionization Radiation

NASA Technical Reports Server (NTRS)

Kim, Myung-Hee Y.; Zeitlin, Cary; Hassler, Donald M.; Cucinotta, Francis A.

2013-01-01

The spectrum of energetic particle radiation and corresponding doses at the surface of Mars is being characterized by the Radiation Assessment Detector (RAD), one of ten science instruments on the Mars Science Laboratory (MSL) Curiosity Rover. The time series of dose rate for the first 300 Sols after landing on Mars on August 6, 2012 is presented here. For the comparison to RAD measurements of dose rate, Martian surface ionization radiation is simulated by utilizing observed space quantities. The GCR primary radiation spectrum is calculated by using the Badhwar-O'Neill 2011 (BO11) galactic cosmic ray (GCR) model, which has been developed by utilizing all balloon and satellite GCR measurements since 1955 and the newer 1997-2012 Advanced Composition Explorer (ACE) measurements. In the BO11 model, solar modulation of the GCR primary radiation spectrum is described in terms of the international smoothed sunspot number and a time delay function. For the transport of the impingent GCR primary radiation through Mars atmosphere, a vertical distribution of atmospheric thickness at each elevation is calculated using the vertical profiles of atmospheric temperature and pressure made by Mars Global Surveyor measurements. At Gale Crater in the southern hemisphere, the seasonal variation of atmospheric thickness is accounted for the daily atmospheric pressure measurements of the MSL Rover Environmental Monitoring Station (REMS) by using low- and high-density models for cool- and warm-season, respectively. The spherically distributed atmospheric distance is traced along the slant path, and the resultant directional shielding by Martian atmosphere is coupled with Curiosity vehicle for dose estimates. We present predictions of dose rate and comparison to the RAD measurements. The simulation agrees to within +/- 20% with the RAD measurements showing clearly the variation of dose rate by heliospheric conditions, and presenting the sensitivity of dose rate by atmospheric pressure, which has been found from the RAD experiments and driven by thermal tides on Martian surface.

Atmospheric changes caused by galactic cosmic rays over the period 1960-2010

NASA Astrophysics Data System (ADS)

Jackman, Charles H.; Marsh, Daniel R.; Kinnison, Douglas E.; Mertens, Christopher J.; Fleming, Eric L.

2016-05-01

The Specified Dynamics version of the Whole Atmosphere Community Climate Model (SD-WACCM) and the Goddard Space Flight Center two-dimensional (GSFC 2-D) models are used to investigate the effect of galactic cosmic rays (GCRs) on the atmosphere over the 1960-2010 time period. The Nowcast of Atmospheric Ionizing Radiation for Aviation Safety (NAIRAS) computation of the GCR-caused ionization rates are used in these simulations. GCR-caused maximum NOx increases of 4-15 % are computed in the Southern polar troposphere with associated ozone increases of 1-2 %. NOx increases of ˜ 1-6 % are calculated for the lower stratosphere with associated ozone decreases of 0.2-1 %. The primary impact of GCRs on ozone was due to their production of NOx. The impact of GCRs varies with the atmospheric chlorine loading, sulfate aerosol loading, and solar cycle variation. Because of the interference between the NOx and ClOx ozone loss cycles (e.g., the ClO + NO2+ M → ClONO2+ M reaction) and the change in the importance of ClOx in the ozone budget, GCRs cause larger atmospheric impacts with less chlorine loading. GCRs also cause larger atmospheric impacts with less sulfate aerosol loading and for years closer to solar minimum. GCR-caused decreases of annual average global total ozone (AAGTO) were computed to be 0.2 % or less with GCR-caused column ozone increases between 1000 and 100 hPa of 0.08 % or less and GCR-caused column ozone decreases between 100 and 1 hPa of 0.23 % or less. Although these computed ozone impacts are small, GCRs provide a natural influence on ozone and need to be quantified over long time periods. This result serves as a lower limit because of the use of the ionization model NAIRAS/HZETRN which underestimates the ion production by neglecting electromagnetic and muon branches of the cosmic ray induced cascade. This will be corrected in future works.

A field assessment of long-term laboratory sediment toxicity tests with the amphipod Hyalella azteca

USGS Publications Warehouse

Ingersoll, Christopher G.; Wang, Ning; Hayward, Jeannie M. R.; Jones, John R.; Jones, Susan B.; Ireland, D. Scott

2005-01-01

Response of the amphipod Hyalella azteca exposed to contaminated sediments for 10 to 42 d in laboratory toxicity tests was compared to responses observed in controlled three-month invertebrate colonization exposures conducted in a pond. Sediments evaluated included a sediment spiked with dichlorodiphenyldichloroethane (DDD) or dilutions of a field sediment collected from the Grand Calumet River (GCR) in Indiana (USA) (contaminated with organic compounds and metals). Consistent effects were observed at the highest exposure concentrations (400 ??g DDD/goc [DDD concentrations normalized to grams of organic carbon (goc) in sedimentl or 4% GCR sediment) on survival, length, and reproduction of amphipods in the laboratory and on abundance of invertebrates colonizing sediments in the field. Effect concentrations for DDD observed for 10-d length and 42-d reproduction of amphipods (e.g., chronic value [ChV] of 66 ??g DDD/goc and 25% inhibition concentration [IC25] of 68 ??g DDD/goc for reproduction) were similar to the lowest effect concentrations for DDD measured on invertebrates colonizing sediment the field. Effect concentrations for GCR sediment on 28-d survival and length and 42-d reproduction and length of amphipods (i.e., ChVs of 0.20-0.66% GCR sediment) provided more conservative effect concentrations compared to 10-d survival or length of amphipods in the laboratory or the response of invertebrates colonizing sediment in the field (e.g., ChVs of 2.2% GCR sediment). Results of this study indicate that use of chronic laboratory toxicity tests with H. azteca and benthic colonization studies should be used to provide conservative estimates of impacts on benthic communities exposed to contaminated sediments. Bioaccumulation of DDD by oligochaetes colonizing the DDD-spiked sediment was similar to results of laboratory sediment tests previously conducted with the oligochaete Lumbriculus variegates, confirming that laboratory exposures can be used to estimate bioaccumulation by oligochaetes exposed in the field. ?? 2005 SETAC.

Computational Model Prediction and Biological Validation Using Simplified Mixed Field Exposures for the Development of a GCR Reference Field

NASA Technical Reports Server (NTRS)

Hada, M.; Rhone, J.; Beitman, A.; Saganti, P.; Plante, I.; Ponomarev, A.; Slaba, T.; Patel, Z.

2018-01-01

The yield of chromosomal aberrations has been shown to increase in the lymphocytes of astronauts after long-duration missions of several months in space. Chromosome exchanges, especially translocations, are positively correlated with many cancers and are therefore a potential biomarker of cancer risk associated with radiation exposure. Although extensive studies have been carried out on the induction of chromosomal aberrations by low- and high-LET radiation in human lymphocytes, fibroblasts, and epithelial cells exposed in vitro, there is a lack of data on chromosome aberrations induced by low dose-rate chronic exposure and mixed field beams such as those expected in space. Chromosome aberration studies at NSRL will provide the biological validation needed to extend the computational models over a broader range of experimental conditions (more complicated mixed fields leading up to the galactic cosmic rays (GCR) simulator), helping to reduce uncertainties in radiation quality effects and dose-rate dependence in cancer risk models. These models can then be used to answer some of the open questions regarding requirements for a full GCR reference field, including particle type and number, energy, dose rate, and delivery order. In this study, we designed a simplified mixed field beam with a combination of proton, helium, oxygen, and iron ions with shielding or proton, helium, oxygen, and titanium without shielding. Human fibroblasts cells were irradiated with these mixed field beam as well as each single beam with acute and chronic dose rate, and chromosome aberrations (CA) were measured with 3-color fluorescent in situ hybridization (FISH) chromosome painting methods. Frequency and type of CA induced with acute dose rate and chronic dose rates with single and mixed field beam will be discussed. A computational chromosome and radiation-induced DNA damage model, BDSTRACKS (Biological Damage by Stochastic Tracks), was updated to simulate various types of CA induced by acute exposures of the mixed field beams used for the experiments. The chromosomes were simulated by a polymer random walk algorithm with restrictions to their respective domains in the nucleus [1]. The stochastic dose to the nucleus was calculated with the code RITRACKS [2]. Irradiation of a target volume by a mixed field of ions was implemented within RITRACKs, and the fields of ions can be delivered over specific periods of time, allowing the simulation of dose-rate effects. Similarly, particles of various types and energies extracted from a pre-calculated spectra of galactic cosmic rays (GCR) can be used in RITRACKS. The number and spatial location of DSBs (DNA double-strand breaks) were calculated in BDSTRACKS using the simulated chromosomes and local (voxel) dose. Assuming that DSBs led to chromosome breaks, and simulating the rejoining of damaged chromosomes occurring during repair, BDSTRACKS produces the yield of various types of chromosome aberrations as a function of time (only final yields are presented). A comparison between experimental and simulation results will be shown.

Radiation exposure for manned Mars surface missions

NASA Technical Reports Server (NTRS)

Simonsen, Lisa C.; Nealy, John E.; Townsend, Lawrence W.; Wilson, John W.

1990-01-01

The Langley cosmic ray transport code and the Langley nucleon transport code (BRYNTRN) are used to quantify the transport and attenuation of galactic cosmic rays (GCR) and solar proton flares through the Martian atmosphere. Surface doses are estimated using both a low density and a high density carbon dioxide model of the atmosphere which, in the vertical direction, provides a total of 16 g/sq cm and 22 g/sq cm of protection, respectively. At the Mars surface during the solar minimum cycle, a blood-forming organ (BFO) dose equivalent of 10.5 to 12 rem/yr due to galactic cosmic ray transport and attenuation is calculated. Estimates of the BFO dose equivalents which would have been incurred from the three large solar flare events of August 1972, November 1960, and February 1956 are also calculated at the surface. Results indicate surface BFO dose equivalents of approximately 2 to 5, 5 to 7, and 8 to 10 rem per event, respectively. Doses are also estimated at altitudes up to 12 km above the Martian surface where the atmosphere will provide less total protection.

Space radiation dose estimates on the surface of Mars

NASA Technical Reports Server (NTRS)

Simonsen, Lisa C.; Nealy, John E.; Townsend, Lawrence W.; Wilson, John W.

1990-01-01

The Langley cosmic ray transport code and the Langley nucleon transport code (BRYNTRN) are used to quantify the transport and attenuation of galactic cosmic rays (GCR) and solar proton flares through the Martian atmosphere. Surface doses are estimated using both a low density and a high density carbon dioxide model of the atmosphere which, in the vertical direction, provides a total of 16 g/sq cm and 22 g/sq cm of protection, respectively. At the Mars surface during the solar minimum cycle, a blood-forming organ (BFO) dose equivalent of 10.5 to 12 rem/yr due to galactic cosmic ray transport and attenuation is calculated. Estimates of the BFO dose equivalents which would have been incurred from the three large solar flare events of August 1972, November 1960, and February 1956 are also calculated at the surface. Results indicate surface BFO dose equivalents of approximately 2 to 5, 5 to 7, and 8 to 10 rem per event, respectively. Doses are also estimated at altitudes up to 12 km above the Martian surface where the atmosphere will provide less total protection.

Selfish cells in altruistic cell society - a theoretical oncology.

PubMed

Chigira, M

1993-09-01

In multicellular organisms, internal evolution of individual cells is strictly forbidden and 'evolutional' DNA replication should be performed only by the sexual reproduction system. Wholistic negative control system called 'homeostasis' serves all service to germ line cells. All somatic cells are altruistic to the germ line cells. However, in malignant tumors, it seems that individual cells replicate and behave 'selfishly' and evolve against the internal microenvironment. Tumor cells only express the occult selfishness which is programmed in normal cells a priori. This phenomenon is based on the failure of identical DNA replication, and results in 'autonomy' and 'anomie' of cellular society as shown in tumor cells. Genetic programs of normal cells connote this cellular autonomy and anomie introduced by the deletion of regulators on structure genes. It is rather paradoxical that the somatic cells get their freedom from wholistic negative regulation programmed internally. However, this is not a true paradox, since multicellular organisms have clearly been evolved from 'monads' in which cells proliferate without wholistic regulation. Somatic cells revolt against germ cell DNA, called 'selfish replicator' by Dawkins. It is an inevitable destiny that the 'selfishness' coded in genome should be revenged by itself. Selfish replicator in germ cell line should be revolted by its selfishness in the expansion of somatic cells, since they have an orthogenesis to get more selfishness in order to increase their genome. Tumor heterogeneity and progression can be fully explained by this self-contradictory process which produces heterogeneous gene copies different from the original clone in the tumor, although 'selfish' gene replication is the final target of being. Furthermore, we have to discard the concept of clonality of tumor cells since genetic instability is a fundamental feature of tumors. Finally, tumor cells and proto-oncogenes can be considered as the ultimate parasite to germ line cells.

Computational Assessment of Naturally Occurring Neutron and Photon Background Radiation Produced by Extraterrestrial Sources

DOE PAGES

Miller, Thomas Martin; de Wet, Wouter C.; Patton, Bruce W.

2015-10-28

In this study, a computational assessment of the variation in terrestrial neutron and photon background from extraterrestrial sources is presented. The motivation of this assessment is to evaluate the practicality of developing a tool or database to estimate background in real time (or near–real time) during an experimental measurement or to even predict the background for future measurements. The extraterrestrial source focused on during this assessment is naturally occurring galactic cosmic rays (GCRs). The MCNP6 transport code was used to perform the computational assessment. However, the GCR source available in MCNP6 was not used. Rather, models developed and maintained bymore » NASA were used to generate the GCR sources. The largest variation in both neutron and photon background spectra was found to be caused by changes in elevation on Earth's surface, which can be as large as an order of magnitude. All other perturbations produced background variations on the order of a factor of 3 or less. The most interesting finding was that ~80% and 50% of terrestrial background neutrons and photons, respectively, are generated by interactions in Earth's surface and other naturally occurring and man-made objects near a detector of particles from extraterrestrial sources and their progeny created in Earth's atmosphere. In conclusion, this assessment shows that it will be difficult to estimate the terrestrial background from extraterrestrial sources without a good understanding of a detector's surroundings. Therefore, estimating or predicting background during a measurement environment like a mobile random search will be difficult.« less

Modulation of GCR in Various Types of Helispheric Magnetic Field

NASA Astrophysics Data System (ADS)

Kobylinski, Z.; Bochorishvili, T.

We make an attempt to compare the modulation of galactic cosmic rays (GCR) as the result of various assumptions referred to heliospheric magnetic field (HMF). The steady state version of 3D Parker cosmic ray transport equation (TPE), with drift included, is solved num erically in the spherically symmetric heliosphere. We take into account four cases of the possible magnetic field configuration: standard Parker HMF, Parker field with modifications in polar direction done by Jokippi and K ta (2) and Smith ando Bieber (3) , Fisk type of field (4). In the last one we assume the existence north and south polar coronal holes in the inner corona with central point inclined from the rotation of the Sun. At the polar regions of the heliosphere the isotropic diffusion of GCR is assumed. The results of calculation s will be discussed in detail. The (4) model more reduces an acces s of galactic particles from polar direction into solar system than others.

Galactic-cosmic-ray-produced 3He in a ferromanganese crust: any supernova 60Fe excess on earth?

PubMed

Basu, S; Stuart, F M; Schnabel, C; Klemm, V

2007-04-06

An excess of 60Fe in 2.4-3.2 x 10(6) year old ferromanganese crust (237 KD) from the deep Pacific Ocean has been considered as evidence for the delivery of debris from a nearby supernova explosion to Earth. Extremely high ;{3}He/;{4}He (up to 6.12 x 10(-3)) and 3He concentrations (up to 8 x 10(9) atoms/g) measured in 237 KD cannot be supernova-derived. The helium is produced by galactic cosmic rays (GCR) and delivered in micrometeorites that have survived atmospheric entry to be trapped by the crust. 60Fe is produced by GCR reactions on Ni in extraterrestrial material. The maximum (3)He/(60)Fe of 237 KD (80-850) is comparable to the GCR (3)He/(60)Fe production ratio (400-500) predicted for Ni-bearing minerals in iron meteorites. The excess 60Fe can be plausibly explained by the presence of micrometeorites trapped by the crust, rather than injection from a supernova source.

Radiation Shielding Optimization on Mars

NASA Technical Reports Server (NTRS)

Slaba, Tony C.; Mertens, Chris J.; Blattnig, Steve R.

2013-01-01

Future space missions to Mars will require radiation shielding to be optimized for deep space transit and an extended stay on the surface. In deep space, increased shielding levels and material optimization will reduce the exposure from most solar particle events (SPE) but are less effective at shielding against galactic cosmic rays (GCR). On the surface, the shielding provided by the Martian atmosphere greatly reduces the exposure from most SPE, and long-term GCR exposure is a primary concern. Previous work has shown that in deep space, additional shielding of common materials such as aluminum or polyethylene does not significantly reduce the GCR exposure. In this work, it is shown that on the Martian surface, almost any amount of aluminum shielding increases exposure levels for humans. The increased exposure levels are attributed to neutron production in the shield and Martian regolith as well as the electromagnetic cascade induced in the Martian atmosphere. This result is significant for optimization of vehicle and shield designs intended for the surface of Mars.

A genetic network that suppresses genome rearrangements in Saccharomyces cerevisiae and contains defects in cancers

PubMed Central

Putnam, Christopher D.; Srivatsan, Anjana; Nene, Rahul V.; Martinez, Sandra L.; Clotfelter, Sarah P.; Bell, Sara N.; Somach, Steven B.; E.S. de Souza, Jorge; Fonseca, André F.; de Souza, Sandro J.; Kolodner, Richard D.

2016-01-01

Gross chromosomal rearrangements (GCRs) play an important role in human diseases, including cancer. The identity of all Genome Instability Suppressing (GIS) genes is not currently known. Here multiple Saccharomyces cerevisiae GCR assays and query mutations were crossed into arrays of mutants to identify progeny with increased GCR rates. One hundred eighty two GIS genes were identified that suppressed GCR formation. Another 438 cooperatively acting GIS genes were identified that were not GIS genes, but suppressed the increased genome instability caused by individual query mutations. Analysis of TCGA data using the human genes predicted to act in GIS pathways revealed that a minimum of 93% of ovarian and 66% of colorectal cancer cases had defects affecting one or more predicted GIS gene. These defects included loss-of-function mutations, copy-number changes associated with reduced expression, and silencing. In contrast, acute myeloid leukaemia cases did not appear to have defects affecting the predicted GIS genes. PMID:27071721

High time resolution observations of the drivers of Forbush decreases

NASA Astrophysics Data System (ADS)

Jordan, A. P.; Spence, H. E.; Blake, J. B.; Mulligan, T. L.; Shaul, D. N.

2008-12-01

The drivers of Forbush decreases in galactic cosmic ray (GCR) fluxes are thought to be magnetic turbulence in the sheath of an interplanetary coronal mass ejection (ICME) and the closed magnetic field lines in the ICME itself. This model, however, is the result of studies utilizing hourly or longer time averaging. Such averaging can smooth over important correlations between variabilities in the GCR flux and those in the interplanetary medium. To test the validity of the current model of Forbush decreases, we analyze a number of Forbush decreases using high time resolution GCR data from the High Sensitivity Telescope (HIST) on Polar and the Spectrometer for INTEGRAL (SPI). We seek causal correlations between the onset of the decrease and structures in the solar wind plasma and interplanetary magnetic field, as measured concurrently with ACE and/or Wind. We find evidence that planar magnetic structures in the sheath preceding the ICME may be a factor in driving the decrease in at least one event.

Calibration of the Galactic Cosmic Ray Flux

NASA Technical Reports Server (NTRS)

Mathew, K. J.; Marti, K.

2004-01-01

We report first Xe data on the cross-calibration of I-129-Xe-129(sub n) ages with conventional CRE ages, a method which is expected to provide information on the long-term constancy of the galactic cosmic ray (GCR) flux. We studied isotopic signatures of Xe released in stepwise heating, decomposition and melting of troilites in the Cape York iron meteorite to identify isotopic shifts in Xe-129 and Xe-131 due to neutron capture in Te-128 and Te-130. We also resolve components due to extinct 129I, spallation and fission Xe. There has recently been much speculation on the constancy of GCR over long time scales, as may be inferred from iron meteorites. If GCRs originate from supernova events, this provides the basis for postulating increased fluxes at locations with higher than average densities of supernovae, specifically in OB-associations. The solar system at present appears to be inside a local bubble between spiral arms and may experience an increased GCR flux.

Modulation of UK lightning and the atmospheric electric circuit by heliospheric magnetic field polarity

NASA Astrophysics Data System (ADS)

Owens, Mathew; Scott, Chris; Lockwood, Mike; Barnard, Luke; Harrison, Giles; Nicoll, Keri; Watt, Clare; Bennett, Alec

2015-04-01

Observational studies have reported solar magnetic modulation of terrestrial lightning on a range of time scales, from days to decades. The proposed mechanism is two-step: lightning rates vary with galactic cosmic ray (GCR) flux incident on Earth, either via changes in atmospheric conductivity and/or direct triggering of lightning. GCR flux is, in turn, primarily controlled by the heliospheric magnetic field (HMF) intensity. Consequently, global changes in lightning rates are expected. This study instead considers HMF polarity, which doesn't greatly affect total GCR flux. Opposing HMF polarities are, however, associated with a 40 to 60% difference in observed UK lightning and thunder rates. As HMF polarity skews the terrestrial magnetosphere from its nominal position, this perturbs local ionospheric potential at high latitudes and local exposure to energetic charged particles from the magnetosphere. We speculate as to the mechanism(s) by which this may, in turn, redistribute the global location and/or intensity of thunderstorm activity.

Study of the Geoeffectiveness and Galactic Cosmic-Ray Response of VarSITI-ISEST Campaign Events in Solar Cycle 24

NASA Astrophysics Data System (ADS)

Aslam, O. P. M.; Badruddin

2017-09-01

We analyze and compare the geomagnetic and galactic cosmic-ray (GCR) response of selected solar events, particularly the campaign events of the group International Study of Earth-affecting Solar Transients (ISEST) of the program Variability of the Sun and Its Terrestrial Impact (VarSITI). These selected events correspond to Solar Cycle 24, and we identified various of their features during their near-Earth passage. We evaluated the hourly data of geomagnetic indices and ground-based neutron monitors and the concurrent data of interplanetary plasma and field parameters. We recognized distinct features of these events and solar wind parameters when the geomagnetic disturbance was at its peak and when the cosmic-ray intensity was most affected. We also discuss the similarities and differences in the geoeffectiveness and GCR response of the solar and interplanetary structures in the light of plasma and field variations and physical mechanism(s), which play a crucial role in influencing the geomagnetic activity and GCR intensity.

Solar flare neon and solar cosmic ray fluxes in the past using gas-rich meteorites

NASA Technical Reports Server (NTRS)

Nautiyal, C. M.; Rao, M. N.

1986-01-01

Methods were developed earlier to deduce the composition of solar flare neon and to determine the solar cosmic ray proton fluxes in the past using etched lunar samples and at present, these techniques are extended to gas rich meteorites. By considering high temperature Ne data points for Pantar, Fayetteville and other gas rich meteorites and by applying the three component Ne-decomposition methods, the solar cosmic ray and galactic cosmic ray produced spallation Ne components from the trapped SF-Ne was resolved. Using appropiate SCR and GCR production rates, in the case of Pantar, for example, a GCR exposure age of 2 m.y. was estimated for Pantar-Dark while Pantar-Light yielded a GCR age of approx. 3 m.y. However the SCR exposure age of Pantar-Dark is two orders of magnitude higher than the average surface exposure ages of lunar soils. The possibility of higher proton fluxes in the past is discussed.

Experimental Plans for Subsystems of a Shock Wave Driven Gas Core Reactor

NASA Technical Reports Server (NTRS)

Kazeminezhad, F.; Anghai, S.

2008-01-01

This Contractor Report proposes a number of plans for experiments on subsystems of a shock wave driven pulsed magnetic induction gas core reactor (PMI-GCR, or PMD-GCR pulsed magnet driven gas core reactor). Computer models of shock generation and collision in a large-scale PMI-GCR shock tube have been performed. Based upon the simulation results a number of issues arose that can only be addressed adequately by capturing experimental data on high pressure (approx.1 atmosphere or greater) partial plasma shock wave effects in large bore shock tubes ( 10 cm radius). There are three main subsystems that are of immediate interest (for appraisal of the concept viability). These are (1) the shock generation in a high pressure gas using either a plasma thruster or pulsed high magnetic field, (2) collision of MHD or gas dynamic shocks, their interaction time, and collision pile-up region thickness, and (3) magnetic flux compression power generation (not included here).

Comparison of Radiation Transport Codes, HZETRN, HETC and FLUKA, Using the 1956 Webber SPE Spectrum

NASA Technical Reports Server (NTRS)

Heinbockel, John H.; Slaba, Tony C.; Blattnig, Steve R.; Tripathi, Ram K.; Townsend, Lawrence W.; Handler, Thomas; Gabriel, Tony A.; Pinsky, Lawrence S.; Reddell, Brandon; Clowdsley, Martha S.;

Selective cooling on land supports cloud formation by cosmic ray during geomagnetic reversals

NASA Astrophysics Data System (ADS)

Kitaba, I.; Hyodo, M.; Nakagawa, T.; Katoh, S.; Dettman, D. L.; Sato, H.

2017-12-01

On geological time scales, the galactic cosmic ray (GCR) flux at the Earth's surface has increased significantly during many short time intervals. There is a growing body of evidence that suggests that climatic cooling occurred during these episodes. Cloud formation by GCR has been claimed as the most likely cause of the linkage. However, the mechanism is not fully understood due to the difficulty of accurately estimating the amount of cloud cover in the geologic past. Our study focused on the geomagnetic field and climate in East Asia. The Earth's magnetic field provides a shield against GCR. The East Asian climate reflects the temperature balance between the Eurasian landmass and the Pacific Ocean that drives monsoon circulation.Two geomagnetic polarity reversals occurred at 780 ka and 1,070 ka. At these times the geomagnetic field decreased to about 10% of its present level causing a near doubling of the GCR flux. Temperature and rainfall amounts during these episodes were reconstructed using pollen in sediment cores from Osaka Bay, Japan. The results show a more significant temperature drop on the Eurasian continent than over the Pacific, and a decrease of summer rainfall in East Asia (i.e. a weakening of East Asian summer monsoon). These observed climate changes can be accounted for if the landmasses were more strongly cooled than the oceans. The simplest mechanism behind such asymmetric cooling is the so-called `umbrella effect' (increased cloud cover blocking solar radiation) that induces greater cooling of objects with smaller heat capacities.

GCR and SPE Radiation Effects in Materials

NASA Technical Reports Server (NTRS)

Waller, Jess; Rojdev, Kristina; Nichols, Charles

2016-01-01

This Year 3 project provides risk reduction data to assess galactic cosmic ray (GCR) and solar particle event (SPE) space radiation damage in materials used in manned low-earth orbit, lunar, interplanetary, and Martian surface missions. Long duration (up to 50 years) space radiation damage is being quantified for materials used in inflatable structures (1st priority), and space suit and habitable composite materials (2nd priority). The data collected has relevance for nonmetallic materials (polymers and composites) used in NASA missions where long duration reliability is needed in continuous or intermittent space radiation fluxes.

A Stochastic Model of Space Radiation Transport as a Tool in the Development of Time-Dependent Risk Assessment

NASA Technical Reports Server (NTRS)

Kim, Myung-Hee Y.; Nounu, Hatem N.; Ponomarev, Artem L.; Cucinotta, Francis A.

2011-01-01

A new computer model, the GCR Event-based Risk Model code (GERMcode), was developed to describe biophysical events from high-energy protons and heavy ions that have been studied at the NASA Space Radiation Laboratory (NSRL) [1] for the purpose of simulating space radiation biological effects. In the GERMcode, the biophysical description of the passage of heavy ions in tissue and shielding materials is made with a stochastic approach that includes both ion track structure and nuclear interactions. The GERMcode accounts for the major nuclear interaction processes of importance for describing heavy ion beams, including nuclear fragmentation, elastic scattering, and knockout-cascade processes by using the quantum multiple scattering fragmentation (QMSFRG) model [2]. The QMSFRG model has been shown to be in excellent agreement with available experimental data for nuclear fragmentation cross sections

Biology of childhood germ cell tumours, focussing on the significance of microRNAs.

PubMed

Murray, M J; Nicholson, J C; Coleman, N

2015-01-01

Genomic and protein-coding transcriptomic data have suggested that germ cell tumours (GCTs) of childhood are biologically distinct from those of adulthood. Global messenger RNA profiles segregate malignant GCTs primarily by histology, but then also by age, with numerous transcripts showing age-related differential expression. Such differences are likely to account for the heterogeneous clinico-pathological behaviour of paediatric and adult malignant GCTs. In contrast, as global microRNA signatures of human tumours reflect their developmental lineage, we hypothesized that microRNA profiles would identify common biological abnormalities in all malignant GCTs owing to their presumed shared origin from primordial germ cells. MicroRNAs are short, non-protein-coding RNAs that regulate gene expression via translational repression and/or mRNA degradation. We showed that all malignant GCTs over-express the miR-371-373 and miR-302/367 clusters, regardless of patient age, histological subtype or anatomical tumour site. Furthermore, bioinformatic approaches and subsequent Gene Ontology analysis revealed that these two over-expressed microRNAs clusters co-ordinately down-regulated genes involved in biologically significant pathways in malignant GCTs. The translational potential of this finding has been demonstrated with the detection of elevated serum levels of miR-371-373 and miR-302/367 microRNAs at the time of malignant GCT diagnosis, with levels falling after treatment. The tumour-suppressor let-7 microRNA family has also been shown to be universally down-regulated in malignant GCTs, because of abundant expression of the regulatory gene LIN28. Low let-7 levels resulted in up-regulation of oncogenes including MYCN, AURKB and LIN28 itself, the latter through a direct feedback mechanism. Targeting LIN28, or restoring let-7 levels, both led to effective inhibition of this pathway. In summary, paediatric malignant GCTs show biological differences from their adult counterparts at a genomic and protein-coding transcriptome level, whereas they both display very similar microRNA expression profiles. These similarities and differences may be exploited for diagnostic and/or therapeutic purposes. © 2014 The Authors. Andrology published by John Wiley & Sons Ltd on behalf of American Society of Andrology.

Anomalous and Galactic Cosmic Ray Intensities at 1 AU During the Approach to the Cycle 24/25 Solar Minimum and Throughout the Last 20 Years

NASA Astrophysics Data System (ADS)

Leske, R. A.; Cummings, A. C.; Mewaldt, R. A.; Cohen, C.; Stone, E. C.; Wiedenbeck, M. E.

2017-12-01

Anomalous cosmic ray (ACR) intensities at 1 AU generally track galactic cosmic ray (GCR) intensities, but with differences between solar polarity cycles: at high rigidities, GCRs reach higher peak intensities during A<0 cycles, while ACRs have been higher at A>0 solar minima. At present, during the approach to an A>0 solar minimum, ACR oxygen above 8 MeV/nucleon as measured by the Advanced Composition Explorer (ACE) has already reached the peak intensities seen during the 2009 A<0 solar minimum, but is still 40% below the levels seen in 1997 during the last A>0 minimum. The GCR iron intensity at 300 MeV/nucleon, on the other hand, is presently comparable to that in 1997 but remains 10% below its record-setting 2009 value. Drift effects play an important role in the modulation of both ACRs and GCRs. Positively charged ions drift inward along the heliospheric current sheet (HCS) during A<0 cycles and their intensities are thus sensitive to the HCS tilt angle, which remained high for much of the last solar cycle. We have previously shown that both ACR and GCR intensities were significantly higher for a given HCS tilt angle during the 2000-2012 A<0 cycle than they were during the prior (1980-1990) A<0 cycle, and this trend appears to be continuing into the new A>0 cycle. But while GCR intensities in 2009 reached the highest levels recorded during the last 50 years, ACR intensities were only similar to those in the 1980s A<0 minimum. Factors such as a weaker interplanetary magnetic field, perhaps with a reduction in the ACR source strength or greater sensitivity of ACRs than GCRs to the HCS tilt angle, may account for the difference in their modulation behavior.We present 20 years of ACR and GCR intensity data acquired by ACE throughout two solar cycles, with emphasis on recent observations, and discuss possible reasons for the differences in the relative behavior of ACRs and GCRs in the different solar cycles.

Atmospheric changes caused by galactic cosmic rays over the period 1960–2010

DOE PAGES

Jackman, Charles H.; Marsh, Daniel R.; Kinnison, Douglas E.; ...

2016-05-13

The Specified Dynamics version of the Whole Atmosphere Community Climate Model (SD-WACCM) and the Goddard Space Flight Center two-dimensional (GSFC 2-D) models are used to investigate the effect of galactic cosmic rays (GCRs) on the atmosphere over the 1960–2010 time period. The Nowcast of Atmospheric Ionizing Radiation for Aviation Safety (NAIRAS) computation of the GCR-caused ionization rates are used in these simulations. GCR-caused maximum NO x increases of 4–15 % are computed in the Southern polar troposphere with associated ozone increases of 1–2 %. NO x increases of ~1–6 % are calculated for the lower stratosphere with associated ozone decreasesmore » of 0.2–1 %. The primary impact of GCRs on ozone was due to their production of NO x. The impact of GCRs varies with the atmospheric chlorine loading, sulfate aerosol loading, and solar cycle variation. Because of the interference between the NO x and ClO x ozone loss cycles (e.g., the ClO + NO 2+ M → ClONO 2+ M reaction) and the change in the importance of ClO x in the ozone budget, GCRs cause larger atmospheric impacts with less chlorine loading. GCRs also cause larger atmospheric impacts with less sulfate aerosol loading and for years closer to solar minimum. GCR-caused decreases of annual average global total ozone (AAGTO) were computed to be 0.2 % or less with GCR-caused column ozone increases between 1000 and 100 hPa of 0.08 % or less and GCR-caused column ozone decreases between 100 and 1 hPa of 0.23 % or less. Although these computed ozone impacts are small, GCRs provide a natural influence on ozone and need to be quantified over long time periods. This result serves as a lower limit because of the use of the ionization model NAIRAS/HZETRN which underestimates the ion production by neglecting electromagnetic and muon branches of the cosmic ray induced cascade. Furthermore, this will be corrected in future works.« less

Renormalization scheme and gauge (in)dependence of the generalized Crewther relation: what are the real grounds of the β-factorization property?

NASA Astrophysics Data System (ADS)

Garkusha, A. V.; Kataev, A. L.; Molokoedov, V. S.

2018-02-01

The problem of scheme and gauge dependence of the factorization property of the renormalization group β-function in the SU( N c ) QCD generalized Crewther relation (GCR), which connects the flavor non-singlet contributions to the Adler and Bjorken polarized sum rule functions, is investigated at the O({a}_s^4) level of perturbation theory. It is known that in the gauge-invariant renormalization \\overline{MS} -scheme this property holds in the QCD GCR at least at this order. To study whether this factorization property is true in all gauge-invariant schemes, we consider the MS-like schemes in QCD and the QED-limit of the GCR in the \\overline{MS} -scheme and in two other gauge-independent subtraction schemes, namely in the momentum MOM and the on-shell OS schemes. In these schemes we confirm the existence of the β-function factorization in the QCD and QED variants of the GCR. The problem of the possible β-factorization in the gauge-dependent renormalization schemes in QCD is studied. To investigate this problem we consider the gauge non-invariant mMOM and MOMgggg-schemes. We demonstrate that in the mMOM scheme at the O({a}_s^3) level the β-factorization is valid for three values of the gauge parameter ξ only, namely for ξ = -3 , -1 and ξ = 0. In the O({a}_s^4) order of PT it remains valid only for case of the Landau gauge ξ = 0. The consideration of these two gauge-dependent schemes for the QCD GCR allows us to conclude that the factorization of RG β-function will always be implemented in any MOM-like renormalization schemes with linear covariant gauge at ξ = 0 and ξ = -3 at the O({a}_s^3) approximation. It is demonstrated that if factorization property for the MS-like schemes is true in all orders of PT, as theoretically indicated in the several works on the subject, then the factorization will also occur in the arbitrary MOM-like scheme in the Landau gauge in all orders of perturbation theory as well.

Atmospheric changes caused by galactic cosmic rays over the period 1960–2010

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

Jackman, Charles H.; Marsh, Daniel R.; Kinnison, Douglas E.

The Specified Dynamics version of the Whole Atmosphere Community Climate Model (SD-WACCM) and the Goddard Space Flight Center two-dimensional (GSFC 2-D) models are used to investigate the effect of galactic cosmic rays (GCRs) on the atmosphere over the 1960–2010 time period. The Nowcast of Atmospheric Ionizing Radiation for Aviation Safety (NAIRAS) computation of the GCR-caused ionization rates are used in these simulations. GCR-caused maximum NO x increases of 4–15 % are computed in the Southern polar troposphere with associated ozone increases of 1–2 %. NO x increases of ~1–6 % are calculated for the lower stratosphere with associated ozone decreasesmore » of 0.2–1 %. The primary impact of GCRs on ozone was due to their production of NO x. The impact of GCRs varies with the atmospheric chlorine loading, sulfate aerosol loading, and solar cycle variation. Because of the interference between the NO x and ClO x ozone loss cycles (e.g., the ClO + NO 2+ M → ClONO 2+ M reaction) and the change in the importance of ClO x in the ozone budget, GCRs cause larger atmospheric impacts with less chlorine loading. GCRs also cause larger atmospheric impacts with less sulfate aerosol loading and for years closer to solar minimum. GCR-caused decreases of annual average global total ozone (AAGTO) were computed to be 0.2 % or less with GCR-caused column ozone increases between 1000 and 100 hPa of 0.08 % or less and GCR-caused column ozone decreases between 100 and 1 hPa of 0.23 % or less. Although these computed ozone impacts are small, GCRs provide a natural influence on ozone and need to be quantified over long time periods. This result serves as a lower limit because of the use of the ionization model NAIRAS/HZETRN which underestimates the ion production by neglecting electromagnetic and muon branches of the cosmic ray induced cascade. Furthermore, this will be corrected in future works.« less

Application of real-time radiation dosimetry using a new silicon LET sensor

NASA Technical Reports Server (NTRS)

Doke, T.; Hayashi, T.; Kikuchi, J.; Nagaoka, S.; Nakano, T.; Sakaguchi, T.; Terasawa, K.; Badhwar, G. D.

1999-01-01

A new type of real-time radiation monitoring device, RRMD-III, consisting of three double-sided silicon strip detectors (DSSDs), has been developed and tested on-board the Space Shuttle mission STS-84. The test succeeded in measuring the linear energy transfer (LET) distribution over the range of 0.2 keV/micrometer to 600 keV/micrometer for 178 h. The Shuttle cruised at an altitude of 300 to 400 km and an inclination angle of 51.6 degrees for 221.3 h, which is equivalent to the International Space Station orbit. The LET distribution obtained for particles was investigated by separating it into galactic cosmic ray (GCR) particles and trapped particles in the South Atlantic Anomaly (SAA) region. The result shows that the contribution in dose-equivalent due to GCR particles is almost equal to that from trapped particles. The total absorbed dose rate during the mission was 0.611 mGy/day; the effective quality factor, 1.64; and the dose equivalent rate, 0.998 mSv/day. The average absorbed dose rates are 0.158 mGy/min for GCR particles and 3.67 mGy/min for trapped particles. The effective quality factors are 2.48 for GCR particles and 1.19 for trapped particles. The absorbed doses obtained by the RRMD-III and a conventional method using TLD (Mg(2)SiO(4)), which was placed around the RRMD-III were compared. It was found that the TLDs showed a lower efficiency, just 58% of absorbed dose registered by the RRMD-III.

Evidence of Energy and Charge Sign Dependence of the Recovery Time for the 2006 December Forbush Event Measured by the PAMELA Experiment

NASA Astrophysics Data System (ADS)

Munini, R.; Boezio, M.; Bruno, A.; Christian, E. C.; de Nolfo, G. A.; Di Felice, V.; Martucci, M.; Merge’, M.; Richardson, I. G.; Ryan, J. M.; Stochaj, S.; Adriani, O.; Barbarino, G. C.; Bazilevskaya, G. A.; Bellotti, R.; Bongi, M.; Bonvicini, V.; Bottai, S.; Cafagna, F.; Campana, D.; Carlson, P.; Casolino, M.; Castellini, G.; De Santis, C.; Galper, A. M.; Karelin, A. V.; Koldashov, S. V.; Koldobskiy, S.; Krutkov, S. Y.; Kvashnin, A. N.; Leonov, A.; Malakhov, V.; Marcelli, L.; Mayorov, A. G.; Menn, W.; Mikhailov, V. V.; Mocchiutti, E.; Monaco, A.; Mori, N.; Osteria, G.; Panico, B.; Papini, P.; Pearce, M.; Picozza, P.; Ricci, M.; Ricciarini, S. B.; Simon, M.; Sparvoli, R.; Spillantini, P.; Stozhkov, Y. I.; Vacchi, A.; Vannuccini, E.; Vasilyev, G.; Voronov, S. A.; Yurkin, Y. T.; Zampa, G.; Zampa, N.; Potgieter, M. S.

2018-01-01

New results on the short-term galactic cosmic-ray (GCR) intensity variation (Forbish decrease) in 2006 December measured by the PAMELA instrument are presented. Forbush decreases are sudden suppressions of the GCR intensities, which are associated with the passage of interplanetary transients such as shocks and interplanetary coronal mass ejections (ICMEs). Most of the past measurements of this phenomenon were carried out with ground-based detectors such as neutron monitors or muon telescopes. These techniques allow only the indirect detection of the overall GCR intensity over an integrated energy range. For the first time, thanks to the unique features of the PAMELA magnetic spectrometer, the Forbush decrease, commencing on 2006 December 14 and following a CME at the Sun on 2006 December 13, was studied in a wide rigidity range (0.4–20 GV) and for different species of GCRs detected directly in space. The daily averaged GCR proton intensity was used to investigate the rigidity dependence of the amplitude and the recovery time of the Forbush decrease. Additionally, for the first time, the temporal variations in the helium and electron intensities during a Forbush decrease were studied. Interestingly, the temporal evolutions of the helium and proton intensities during the Forbush decrease were found to be in good agreement, while the low rigidity electrons (< 2 GV) displayed a faster recovery. This difference in the electron recovery is interpreted as a charge sign dependence introduced by drift motions experienced by the GCRs during their propagation through the heliosphere.

Transient Cosmic-ray Events beyond the Heliopause: Interpreting Voyager-1 Observations

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

Kóta, J.; Jokipii, J. R.

In 2013 March and 2014 May, Voyager-1 ( V1 ) experienced small but significant increases in the flux of galactic cosmic rays (GCRs) in the hundred MeV/n range. Additionally, V1 also saw episodic depletion of GCR flux around perpendicular pitch angles. We discuss the pitch-angle distribution and the time profiles of these events. In a previous paper, we interpreted the 2013 “bump” as the GCRs remotely sensing a shock that reached the magnetic field line passing through V1 : particles gained energy as they were reflected on the approaching region of the stronger magnetic field of the disturbance. Here, wemore » point out that energy gain is not restricted to reflected particles—GCRs passing through the disturbance also gain energy. The effect should be present in a broad range of pitch angles with the maximum increase of GCR intensity predicted to occur at the critical reflection angle. In this paper, the shock is not step-like, but a gradual increase of the magnetic field strength, B , taking a few days, in agreement with V1 measurements. This smoothens the profile of the predicted bump in the GCR flux. We also address the linear episodic decreases seen around perpendicular pitch angles. These events are interpreted in terms of adiabatic cooling behind the shock due to the slow weakening of B . We present simple numerical model calculations and find that a gradual shock followed by a slow decrease of B , as observed, may account for both the episodic increases and the anisotropic depletion of GCR fluxes.« less

Multi-Scale Model of Galactic Cosmic Ray Effects on the Hippocampus

NASA Astrophysics Data System (ADS)

Cucinotta, Francis

An important concern for risk assessment from galactic cosmic ray (GCR) exposures is impacts to the central nervous systems including changes in cognition, and associations with increased risk of Alzheimer’s disease (AD). AD, which affects about 50 percent of the population above age 80-yr, is a degenerative disease that worsens with time after initial onset leading to death, and has no known cure. AD is difficult to detect at early stages, and the small number of epidemiology studies that have considered the possibility have not identified an association with low dose radiation. However, experimental studies in transgenic mice suggest the possibility exits. We discuss modeling approaches to consider mechanisms whereby GCR would accelerate the occurrence of AD to earlier ages. Biomarkers of AD include Amyloid beta plaques, and neurofibrillary tangles (NFT) made up of aggregates of the hyper-phosphorylated form of the micro-tubule associated, tau protein. Related markers include synaptic degeneration, dendritic spine loss, and neuronal cell loss through apoptosis. GCR may affect these processes by causing oxidative stress, aberrant signaling following DNA damage, and chronic neuro-inflammation. Cell types considered in multi-scale models are neurons, astrocytes, and microglia. We developed biochemical and cell kinetics models of DNA damage signaling related to glycogen synthase kinase-3 beta and neuro-inflammation, and considered approaches to develop computer simulations of GCR induced cell interactions and their relationships to Amyloid beta plaques and NFTs. Comparison of model results to experimental data for the age specific development of plaques in transgenic mice and predictions of space radiation effects will be discussed.

Radiation health for a Mars mission

NASA Technical Reports Server (NTRS)

Robbins, Donald E.

1992-01-01

Uncertainties in risk assessments for exposure of a Mars mission crew to space radiation place limitations on mission design and operation. Large shielding penalties are imposed in order to obtain acceptable safety margins. Galactic cosmic rays (GCR) and solar particle events (SPE) are the major concern. A warning system and 'safe-haven' are needed to protect the crew from large SPE which produce lethal doses. A model developed at NASA Johnson Space Center (JSC) to describe solar modulation of GCR intensities reduces that uncertainty to less than 10 percent. Radiation transport models used to design spacecraft shielding have large uncertainties in nuclear fragmentation cross sections for GCR which interact with spacecraft materials. Planned space measurements of linear energy transfer (LET) spectra behind various shielding thicknesses will reduce uncertainties in dose-versus-shielding thickness relationships to 5-10 percent. The largest remaining uncertainty is in biological effects of space radiation. Data on effects of energetic ions in human are nonexistent. Experimental research on effects in animals and cell is needed to allow extrapolation to the risk of carcinogenesis in humans.

Simulation of the GCR spectrum in the Mars curiosity rover's RAD detector using MCNP6

NASA Astrophysics Data System (ADS)

Ratliff, Hunter N.; Smith, Michael B. R.; Heilbronn, Lawrence

2017-08-01

The paper presents results from MCNP6 simulations of galactic cosmic ray (GCR) propagation down through the Martian atmosphere to the surface and comparison with RAD measurements made there. This effort is part of a collaborative modeling workshop for space radiation hosted by Southwest Research Institute (SwRI). All modeling teams were tasked with simulating the galactic cosmic ray (GCR) spectrum through the Martian atmosphere and the Radiation Assessment Detector (RAD) on-board the Curiosity rover. The detector had two separate particle acceptance angles, 4π and 30 ° off zenith. All ions with Z = 1 through Z = 28 were tracked in both scenarios while some additional secondary particles were only tracked in the 4π cases. The MCNP6 4π absorbed dose rate was 307.3 ± 1.3 μGy/day while RAD measured 233 μGy/day. Using the ICRP-60 dose equivalent conversion factors built into MCNP6, the simulated 4π dose equivalent rate was found to be 473.1 ± 2.4 μSv/day while RAD reported 710 μSv/day.

Ultra-Heavy Galactic Cosmic Ray Abundances from the SuperTIGER Instrument: evidence for an OB association origin of GCR

NASA Astrophysics Data System (ADS)

Murphy, Ryan; Supertiger Collaboration

2017-01-01

We report Galactic Cosmic Ray (GCR) abundances of elements from 26Fe to 40Zr measured by the SuperTIGER (Trans-Iron Galactic Element Recorder) instrument during 55 days of exposure on a long-duration balloon flight over Antarctica. SuperTIGER measures charge (Z) and energy (E) using a combination of three scintillator and two Cherenkov detectors, and employs a scintillating fiber hodoscope for event trajectory determination. These observations resolve elemental abundances in this charge range with single-element resolution and good statistics. We also derived GCR source abundances, which support a model of cosmic-ray origin in which the source material consists of a mixture of 19-6+ 11 % material from massive stars and 81% normal interstellar medium (ISM) material with solar system abundances. The results also show a preferential acceleration, ordered by atomic mass (A), of refractory elements over volatile elements by a factor of 4. Both the refractory and volatile elements show a mass-dependent enhancement with similar mass dependence. (now AIP Congressional Science Fellow).

Cancer Risk Map for the Surface of Mars

NASA Technical Reports Server (NTRS)

Kim, Myung-Hee Y.; Cucinotta, Francis A.

2011-01-01

We discuss calculations of the median and 95th percentile cancer risks on the surface of Mars for different solar conditions. The NASA Space Radiation Cancer Risk 2010 model is used to estimate gender and age specific cancer incidence and mortality risks for astronauts exploring Mars. Organ specific fluence spectra and doses for large solar particle events (SPE) and galactic cosmic rays (GCR) at various levels of solar activity are simulated using the HZETRN/QMSFRG computer code, and the 2010 version of the Badhwar and O Neill GCR model. The NASA JSC propensity model of SPE fluence and occurrence is used to consider upper bounds on SPE fluence for increasing mission lengths. In the transport of particles through the Mars atmosphere, a vertical distribution of Mars atmospheric thickness is calculated from the temperature and pressure data of Mars Global Surveyor, and the directional cosine distribution is implemented to describe the spherically distributed atmospheric distance along the slant path at each elevation on Mars. The resultant directional shielding by Mars atmosphere at each elevation is coupled with vehicle and body shielding for organ dose estimates. Astronaut cancer risks are mapped on the global topography of Mars, which was measured by the Mars Orbiter Laser Altimeter. Variation of cancer risk on the surface of Mars is due to a 16-km elevation range, and the large difference is obtained between the Tharsis Montes (Ascraeus, Pavonis, and Arsia) and the Hellas impact basin. Cancer incidence risks are found to be about 2-fold higher than mortality risks with a disproportionate increase in skin and thyroid cancers for all astronauts and breast cancer risk for female astronauts. The number of safe days on Mars to be below radiation limits at the 95th percent confidence level is reported for several Mission design scenarios.

Organ Dose Assessment and Evaluation of Cancer Risk on Mars Surface

NASA Technical Reports Server (NTRS)

Kim, Myung-Hee; Cucinotta, Francis A.

2011-01-01

Organ specific fluence spectra and doses for large solar particle events (SPE) and galactic cosmic rays (GCR) at various levels of solar activity are simulated on the surface of Mars using the HZETRN/QMSFRG computer code and the 2010 version of the Badhwar and O Neill GCR model. The NASA JSC propensity model of SPE fluence and occurrence is used to consider upper bounds on SPE fluence for increasing mission lengths. To account for the radiation transmission through the Mars atmosphere, a vertical distribution of Mars atmospheric thickness is calculated from the temperature and pressure data of Mars Global Surveyor. To describe the spherically distributed atmospheric distance on the Mars surface at each elevation, the directional cosine distribution is implemented. The resultant directional shielding by Mars atmosphere at each elevation is then coupled with vehicle and body shielding for organ dose estimates. Finally, cancer risks for astronauts exploring Mars can be assessed by applying the NASA Space Radiation Cancer Risk 2010 model with the resultant organ dose estimates. Variations of organ doses and cancer risk quantities on the surface of Mars, which are due to a 16-km elevation range between the Tharsis Montes and the Hellas impact basin, are visualized on the global topography of Mars measured by the Mars Orbiter Laser Altimeter. It is found that cancer incidence risks are about 2-fold higher than mortality risks with a disproportionate increase in skin and thyroid cancers for male and female astronauts and in breast cancer for female astronauts. The number of safe days, defined by the upper 95% percent confidence level to be below cancer limits, on Mars is analyzed for several Mars mission design scenarios.

Issues in deep space radiation protection

NASA Technical Reports Server (NTRS)

Wilson, J. W.; Shinn, J. L.; Tripathi, R. K.; Singleterry, R. C.; Clowdsley, M. S.; Thibeault, S. A.; Cheatwood, F. M.; Schimmerling, W.; Cucinotta, F. A.; Badhwar, G. D.;

Charged particles radiation measurements with Liulin-MO dosimeter of FREND instrument aboard ExoMars Trace Gas Orbiter during the transit and in high elliptic Mars orbit

NASA Astrophysics Data System (ADS)

Semkova, Jordanka; Koleva, Rositza; Benghin, Victor; Dachev, Tsvetan; Matviichuk, Yuri; Tomov, Borislav; Krastev, Krasimir; Maltchev, Stephan; Dimitrov, Plamen; Mitrofanov, Igor; Malahov, Alexey; Golovin, Dmitry; Mokrousov, Maxim; Sanin, Anton; Litvak, Maxim; Kozyrev, Andrey; Tretyakov, Vladislav; Nikiforov, Sergey; Vostrukhin, Andrey; Fedosov, Fedor; Grebennikova, Natalia; Zelenyi, Lev; Shurshakov, Vyacheslav; Drobishev, Sergey

2018-03-01

ExoMars is a joint ESA-Rosscosmos program for investigating Mars. Two missions are foreseen within this program: one consisting of the Trace Gas Orbiter (TGO), that carries scientific instruments for the detection of trace gases in the Martian atmosphere and for the location of their source regions, plus an Entry, Descent and landing demonstrator Module (EDM), launched on March 14, 2016; and the other, featuring a rover and a surface platform, with a launch date of 2020. On October 19, 2016 TGO was inserted into high elliptic Mars' orbit. The dosimetric telescope Liulin-MO for measuring the radiation environment onboard the ExoMars 2016 TGO is a module of the Fine Resolution Epithermal Neutron Detector (FREND). Here we present first results from measurements of the charged particle fluxes, dose rates, Linear Energy Transfer (LET) spectra and estimation of dose equivalent rates in the interplanetary space during the cruise of TGO to Mars and first results from dosimetric measurements in high elliptic Mars' orbit. A comparison is made with the dose rates obtained by RAD instrument onboard Mars Science Laboratory during the cruise to Mars in 2011-2012 and with the Galactic Cosmic Rays (GCR) count rates provided by other particle detectors currently in space. The average measured dose rate in Si from GCR during the transit to Mars for the period April 22-September 15, 2016 is 372 ± 37 μGy d-1 and 390 ± 39 μGy d-1 in two perpendicular directions. The dose equivalent rate from GCR for the same time period is about 2 ± 0.3 mSv d-1. This is in good agreement with RAD results for radiation dose rate in Si from GCR in the interplanetary space, taking into account the different solar activity during the measurements of both instruments. About 10% increase of the dose rate, and 15% increase of the dose equivalent rate for 10.5 months flight is observed. It is due to the increase of Liulin-MO particle fluxes for that period and corresponds to the overall GCR intensity increase during the declining phase of the solar activity. Data show that during the cruise to Mars and back (6 months in each direction), taken during the declining of solar activity, the crewmembers of future manned flights to Mars will accumulate at least 60% of the total dose limit for the cosmonaut's/astronaut's career in case their shielding conditions are close to the average shielding of Liulin-MO detectors-about 10 g cm-2. The dosimetric measurements in high elliptic Mars' orbit demonstrate strong dependence of the GCR fluxes near the TGO pericenter on satellite's field of view shadowed by Mars.

The protective function of noncoding DNA in genome defense of eukaryotic male germ cells.

PubMed

Qiu, Guo-Hua; Huang, Cuiqin; Zheng, Xintian; Yang, Xiaoyan

2018-04-01

Peripheral and abundant noncoding DNA has been hypothesized to protect the genome and the central protein-coding sequences against DNA damage in somatic genome. In the cytosol, invading exogenous nucleic acids may first be deactivated by small RNAs encoded by noncoding DNA via mechanisms similar to the prokaryotic CRISPR-Cas system. In the nucleus, the radicals generated by radiation in the cytosol, radiation energy and invading exogenous nucleic acids are absorbed, blocked and/or reduced by peripheral heterochromatin, and damaged DNA in heterochromatin is removed and excluded from the nucleus to the cytoplasm through nuclear pore complexes. To further strengthen the hypothesis, this review summarizes the experimental evidence supporting the protective function of noncoding DNA in the genome of male germ cells. Based on these data, this review provides evidence supporting the protective role of noncoding DNA in the genome defense of sperm genome through similar mechanisms to those of the somatic genome.

Shielding materials for highly penetrating space radiations

NASA Technical Reports Server (NTRS)

Kiefer, Richard L.; Orwoll, Robert A.

1995-01-01

Interplanetary travel involves the transfer from an Earth orbit to a solar orbit. Once outside the Earth's magnetosphere, the major sources of particulate radiation are solar cosmic rays (SCR's) and galactic cosmic rays (GCR's). Intense fluxes of SCR's come from solar flares and consist primarily of protons with energies up to 1 GeV. The GCR consists of a low flux of nuclei with energies up to 10(exp 10) GeV. About 70 percent of the GCR are protons, but a small amount (0.6 percent) are nuclei with atomic numbers greater than 10. High energy charged particles (HZE) interact with matter by transferring energy to atomic electrons in a Coulomb process and by reacting with an atomic nucleus. Energy transferred in the first process increases with the square of the atomic number, so particles with high atomic numbers would be expected to lose large amounts of energy by this process. Nuclear reactions produced by (HZE) particles produce high-energy secondary particles which in turn lose energy to the material. The HZE nuclei are a major concern for radiation protection of humans during interplanetary missions because of the very high specific ionization of both primary and secondary particles. Computer codes have been developed to calculate the deposition of energy by very energetic charged particles in various materials. Calculations show that there is a significant buildup of secondary particles from nuclear fragmentation and Coulomb dissociation processes. A large portion of these particles are neutrons. Since neutrons carry no charge, they only lose energy by collision or reaction with a nucleus. Neutrons with high energies transfer large amounts of energy by inelastic collisions with nuclei. However, as the neutron energy decreases, elastic collisions become much more effective for energy loss. The lighter the nucleus, the greater the fraction of the neutron's kinetic energy that can be lost in an elastic collision. Thus, hydrogen-containing materials such as polymers are most effective in reducing the energy of neutrons. Once neutrons are reduced to very low energies, the probability for undergoing a reaction with a nucleus (the cross section) becomes very high. The product of such a reaction is often radioactive and can involve the release of a significant amount of energy. Thus, it is important to provide protection from low energy neutrons during a long duration space flight. Among the light elements, lithium and boron each have an isotope with a large thermal neutron capture cross section, Li-6 and B-10. However, B-10 is more abundant in the naturally-occurring element than Li-6, has a thermal neutron capture cross section four times that of Li-6, and produces the stable products, He-4 and Li-7 in the interaction while Li-6 produces radioactive tritium (H-3). Thus, boron is the best light-weight material for thermal neutron absorption in spacecraft. The work on this project was focused in two areas: computer design where existing computer codes were used, and in some cases modified, to calculate the propagation and interactions of high energy charged particles through various media, and materials development where boron was incorporated into high performance materials.

Radiation Measured with Different Dosimeters for ISS-Expedition 18-19/ULF2 on Board International Space Station during Solar Minimum

NASA Technical Reports Server (NTRS)

Zhou, Dazhuang; Gaza, R.; Roed, Y.; Semones, E.; Lee, K.; Steenburgh, R.; Johnson, S.; Flanders, J.; Zapp, N.

2010-01-01

Radiation field of particles in low Earth orbit (LEO) is mainly composed of galactic cosmic rays (GCR), solar energetic particles and particles in SAA (South Atlantic Anomaly). GCR are modulated by solar activity, at the period of solar minimum activity, GCR intensity is at maximum and the main contributor for space radiation is GCR. At present for space radiation measurements conducted by JSC (Johnson Space Center) SRAG (Space Radiation Analysis Group), the preferred active dosimeter sensitive to all LET (Linear Energy Transfer) is the tissue equivalent proportional counter (TEPC); the preferred passive dosimeters are thermoluminescence dosimeters (TLDs) and optically stimulated luminescence dosimeters (OSLDs) sensitive to low LET as well as CR-39 plastic nuclear track detectors (PNTDs) sensitive to high LET. For the method using passive dosimeters, radiation quantities for all LET can be obtained by combining radiation results measured with TLDs/OSLDs and CR-39 PNTDs. TEPC, TLDs/OSLDs and CR-39 detectors were used to measure the radiation field for the ISS (International Space Station) - Expedition 18-19/ULF2 space mission which was conducted from 15 November 2008 to 31 July 2009 - near the period of the recent solar minimum activity. LET spectra (differential and integral fluence, absorbed dose and dose equivalent) and radiation quantities were measured for positions TEPC, TESS (Temporary Sleeping Station, inside the polyethylene lined sleep station), SM-P 327 and 442 (Service Module - Panel 327 and 442). This paper presents radiation LET spectra measured with TEPC and CR-39 PNTDs and radiation dose measured with TLDs/OSLDs as well as the radiation quantities combined from results measured with passive dosimeters.

Global clinical response in Cushing’s syndrome patients treated with mifepristone

PubMed Central

Katznelson, Laurence; Loriaux, D Lynn; Feldman, David; Braunstein, Glenn D; Schteingart, David E; Gross, Coleman

2014-01-01

Objective Mifepristone, a glucocorticoid receptor antagonist, improves clinical status in patients with Cushing’s syndrome (CS). We examined the pattern, reliability and correlates of global clinical response (GCR) assessments during a 6-month clinical trial of mifepristone in CS. Design Post hoc analysis of secondary end-point data from a 24-week multicentre, open-label trial of mifepristone (300–1200mg daily) in CS. Intraclass correlation coefficient (ICC) was used to examine rater concordance, and drivers of clinical improvement were determined by multivariate regression analysis. Patients Forty-six adult patients with refractory CS along with diabetes mellitus type 2 or impaired glucose tolerance, and/or a diagnosis of hypertension. Measurements Global clinical assessment made by three independent reviewers using a three-point ordinal scale (+1 = improvement; 0=no change; −1=worsening) based on eight broad clinical categories including glucose control, lipids, blood pressure, body composition, clinical appearance, strength, psychiatric/cognitive symptoms and quality of life at Weeks 6, 10, 16, and 24. Results Positive GCR increased progressively over time with 88% of patients having improved at Week 24 (P<0·001). The full concordance among reviewers occurred in 76·6% of evaluations resulting in an ICC of 0·652 (P<0·001). Changes in body weight (P<0·0001), diastolic blood pressure (P<0·0001), two-hour postoral glucose challenge glucose concentration (P = 0·0003), and Cushingoid appearance (P=0·022) were strong correlates of GCR. Conclusions Mifepristone treatment for CS results in progressive clinical improvement. Overall agreement among clinical reviewers was substantial and determinants of positive GCR included change in weight, blood pressure, glucose levels and appearance. PMID:24102404

Space Radiation Hazards on Human Missions to the Moon and Mars

NASA Astrophysics Data System (ADS)

Townsend, L.

2004-12-01

One of the most significant health risks for humans exploring Earth's moon and Mars is exposure to the harsh space radiation environment. Crews on these exploration missions will be exposed to a complex mixture of very energetic particles. Chronic exposures to the ever-present background galactic cosmic ray (GCR) spectrum consisting of various fluxes of all naturally - occurring chemical elements are combined with infrequent, possibly acute exposures to large fluxes of solar energetic particles, consisting of protons and heavier particles. The GCR environment is primarily a concern for stochastic effects, such as the induction of cancer, with subsequent mortality in many cases, and late deterministic effects, such as cataracts and possible damage to the central nervous system. An acute radiation syndrome response ("radiation sickness") is not possible from the GCR environment since the organ doses are well below levels of concern. Unfortunately, the actual risks of cancer induction and mortality for the very important high-energy heavy ion component of the GCR spectrum are essentially unknown. The sporadic occurrence of extremely large solar energetic particle events, usually associated with intense solar activity, is also a major concern for Lunar and Mars missions because of the possible manifestation of acute effects from the accompanying high doses of such radiations, especially acute radiation syndrome effects such as nausea, emesis, hemorrhaging or possibly even death. Large solar energetic particle events can also contribute significantly to crew risks from cancer mortality. In this presentation an overview of current estimates of critical organ doses and equivalent doses for crews of Lunar and Mars bases and on those on transits between Earth and Mars is presented. Possible methods of mitigating these radiation exposures by shielding, thereby reducing the associated health risks to crews, are also described.

Variations in the GCR Flux Associated with Heliospheric Transient Structures Near the August 20, 2006 Forbush Decrease

NASA Astrophysics Data System (ADS)

Mulligan, T.; Blake, J.; Spence, H. E.; Jordan, A. P.; Shaul, D.; Quenby, J.

2007-12-01

On August 20, 2006 a Forbush decrease observed at Polar in the Earth's magnetosphere was also seen at the INTEGRAL spacecraft outside the magnetosphere during a very active time in the solar wind. Data from Polar HIST and from INTEGRAL's Ge detector saturation rate (GEDSAT), which measures the GCR background with a threshold of ~200 MeV, show similar, short-period GCR variations in and around the Forbush decrease. The solar wind magnetic field and plasma conditions during this time reveals three interplanetary shocks present in the days leading up to and including the Forbush decrease. The first two shocks are driven by interplanetary coronal mass ejections (ICMEs) and the last one by a high-speed stream. However, the solar wind following these shocks and during the Forbush decrease is not particularly geoeffective. The Forbush decrease, which begins at ~1200 UT on August 20, 2006 is the largest intensity change during this active time, but there are many others on a variety of timescales. Looking at more than 14 consecutive hours of INTEGRAL and Polar data on August 21, 2006 shows great similarities in the time history of the measurements made aboard the two satellites coupled with differences that must be due to GCR variability on a scale size of the order or less than their separation distance. Despite the spacecraft separation of over 25 Re, many of the larger intensity fluctuations remain identical at both satellites. Autocorrelation and power spectral analyses have shown these are not ar-n processes and that these fluctuations are statistically significant. Such analyses can be done with high confidence because both detectors aboard Polar and INTEGRAL have large geometric factors that generate high count rates on the order of 1000 particles per spin, ensuring rigorous, statistically significant samples.

A 3D Monte Carlo model of radiation affecting cells, and its application to neuronal cells and GCR irradiation

NASA Astrophysics Data System (ADS)

Ponomarev, Artem; Sundaresan, Alamelu; Kim, Angela; Vazquez, Marcelo E.; Guida, Peter; Kim, Myung-Hee; Cucinotta, Francis A.

A 3D Monte Carlo model of radiation transport in matter is applied to study the effect of heavy ion radiation on human neuronal cells. Central nervous system effects, including cognitive impairment, are suspected from the heavy ion component of galactic cosmic radiation (GCR) during space missions. The model can count, for instance, the number of direct hits from ions, which will have the most affect on the cells. For comparison, the remote hits, which are received through δ-rays from the projectile traversing space outside the volume of the cell, are also simulated and their contribution is estimated. To simulate tissue effects from irradiation, cellular matrices of neuronal cells, which were derived from confocal microscopy, were simulated in our model. To produce this realistic model of the brain tissue, image segmentation was used to identify cells in the images of cells cultures. The segmented cells were inserted pixel by pixel into the modeled physical space, which represents a volume of interacting cells with periodic boundary conditions (PBCs). PBCs were used to extrapolate the model results to the macroscopic tissue structures. Specific spatial patterns for cell apoptosis are expected from GCR, as heavy ions produce concentrated damage along their trajectories. The apoptotic cell patterns were modeled based on the action cross sections for apoptosis, which were estimated from the available experimental data. The cell patterns were characterized with an autocorrelation function, which values are higher for non-random cell patterns, and the values of the autocorrelation function were compared for X rays and Fe ion irradiations. The autocorrelation function indicates the directionality effects present in apoptotic neuronal cells from GCR.

Constitutive Modeling of the Flow Stress of GCr15 Continuous Casting Bloom in the Heavy Reduction Process

NASA Astrophysics Data System (ADS)

Ji, Cheng; Wang, Zilin; Wu, Chenhui; Zhu, Miaoyong

2018-04-01

According to the calculation results of a 3D thermomechanical-coupled finite-element (FE) model of GCr15 bearing steel bloom during a heavy reduction (HR) process, the variation ranges in the strain rate and strain under HR were described. In addition, the hot deformation behavior of the GCr15 bearing steel was studied over the temperature range from 1023 K to 1573 K (750 °C to 1300 °C) with strain rates of 0.001, 0.01, and 0.1 s-1 in single-pass thermosimulation compression experiments. To ensure the accuracy of the constitutive model, the temperature range was divided into two temperature intervals according to the fully austenitic temperature of GCr15 steel [1173 K (900 °C)]. Two sets of material parameters for the constitutive model were derived based on the true stress-strain curves of the two temperature intervals. A flow stress constitutive model was established using a revised Arrhenius-type constitutive equation, which considers the relationships among the material parameters and true strain. This equation describes dynamic softening during hot compression processes. Considering the effect of glide and climb on the deformation mechanism, the Arrhenius-type constitutive equation was modified by a physically based approach. This model is the most accurate over the temperatures ranging from 1173 K to 1573 K (900 °C to 1300 °C) under HR deformation conditions (ignoring the range from 1273 K to 1573 K (1000 °C to 1300 °C) with a strain rate of 0.1 s-1). To ensure the convergence of the FE calculation, an approximated method was used to estimate the flow stress at temperatures greater than 1573 K (1300 °C).

An Algorithm for the Transport of Anisotropic Neutrons

NASA Technical Reports Server (NTRS)

Tweed, J.

2005-01-01

One major obstacle to human space exploration is the possible limitations imposed by the adverse effect of long-term exposure to the space environment. Even before human spaceflight began, the potentially brief exposure of astronauts to the very intense random solar particle events (SPE) were of great concern. A new challenge appears in deep space exploration from exposure to the low-intensity heavy-ion flux of the galactic cosmic rays (GCR) since the missions are of long duration and the accumulated GCR exposures can be high. Because cancer induction rates increase behind low to rather large thicknesses of aluminum shielding, according to available biological data on mammalian exposures to GCR like ions, the shield requirements for a Mars mission are prohibitively expensive in terms of mission launch costs. Therefore, a critical issue in the Human Exploration and Development of Space enterprise is cost effective mitigation of risk associated with ionizing radiation exposure. In order to estimate astronaut risk to GCR exposure and associated cancer risks and health hazards, it is necessary to do shield material studies. To determine an optimum radiation shield material it is necessary to understand nuclear interaction processes such as fragmentation and secondary particle production which is a function of energy dependent cross sections. This requires knowledge of material transmission characteristics either through laboratory testing or improved theoretical modeling. Here ion beam transport theory is of importance in that testing of materials in the laboratory environment generated by particle accelerators is a necessary step in materials development and evaluation for space use. The approximations used in solving the Boltzmann transport equation for the space setting are often not sufficient for laboratory work and those issues are a major emphasis of the present work.

ISOLATED WOLF-RAYET STARS AND O SUPERGIANTS IN THE GALACTIC CENTER REGION IDENTIFIED VIA PASCHEN-{alpha} EXCESS

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

Mauerhan, J. C.; Stolovy, S. R.; Cotera, A.

We report the discovery of 19 hot, evolved, massive stars near the Galactic center region (GCR). These objects were selected for spectroscopy owing to their detection as strong sources of Paschen-{alpha} (P{alpha}) emission-line excess, following a narrowband imaging survey of the central 0.{sup 0}65 x 0.{sup 0}25 (l, b) around Sgr A* with the Hubble Space Telescope. Discoveries include six carbon-type (WC) and five nitrogen-type (WN) Wolf-Rayet stars, six O supergiants, and two B supergiants. Two of the O supergiants have X-ray counterparts having properties consistent with solitary O stars and colliding-wind binaries. The infrared photometry of 17 stars ismore » consistent with the Galactic center distance, but 2 of them are located in the foreground. Several WC stars exhibit a relatively large infrared excess, which is possibly thermal emission from hot dust. Most of the stars appear scattered throughout the GCR, with no relation to the three known massive young clusters; several others lie near the Arches and Quintuplet clusters and may have originated within one of these systems. The results of this work bring the total sample of Wolf-Rayet (WR) stars in the GCR to 88. All sources of strong P{alpha} excess have been identified in the area surveyed with HST, which implies that the sample of WN stars in this region is near completion, and is dominated by late (WNL) types. The current WC sample, although probably not complete, is almost exclusively dominated by late (WCL) types. The observed WR subtype distribution in the GCR is a reflection of the intrinsic rarity of early subtypes (WNE and WCE) in the inner Galaxy, an effect that is driven by metallicity.« less

Radiation protection using Martian surface materials in human exploration of Mars

NASA Technical Reports Server (NTRS)

Kim, M. H.; Thibeault, S. A.; Wilson, J. W.; Heilbronn, L.; Kiefer, R. L.; Weakley, J. A.; Dueber, J. L.; Fogarty, T.; Wilkins, R.

2001-01-01

To develop materials for shielding astronauts from the hazards of GCR, natural Martian surface materials are considered for their potential as radiation shielding for manned Mars missions. The modified radiation fluences behind various kinds of Martian rocks and regolith are determined by solving the Boltzmann equation using NASA Langley's HZETRN code along with the 1977 Solar Minimum galactic cosmic ray environmental model. To develop structural shielding composite materials for Martian surface habitats, theoretical predictions of the shielding properties of Martian regolith/polyimide composites has been computed to assess their shielding effectiveness. Adding high-performance polymer binders to Martian regolith to enhance structural properties also enhances the shielding properties of these composites because of the added hydrogenous constituents. Heavy ion beam testing of regolith simulant/polyimide composites is planned to validate this prediction. Characterization and proton beam tests are performed to measure structural properties and to compare the shielding effects on microelectronic devices, respectively.

Production of Viable Gametes without Meiosis in Maize Deficient for an ARGONAUTE Protein[W

PubMed Central

Singh, Manjit; Goel, Shalendra; Meeley, Robert B.; Dantec, Christelle; Parrinello, Hugues; Michaud, Caroline; Leblanc, Olivier; Grimanelli, Daniel

2011-01-01

Apomixis is a form of asexual reproduction through seeds in angiosperms. Apomictic plants bypass meiosis and fertilization, developing offspring that are genetically identical to their mother. In a genetic screen for maize (Zea mays) mutants mimicking aspects of apomixis, we identified a dominant mutation resulting in the formation of functional unreduced gametes. The mutant shows defects in chromatin condensation during meiosis and subsequent failure to segregate chromosomes. The mutated locus codes for AGO104, a member of the ARGONAUTE family of proteins. AGO104 accumulates specifically in somatic cells surrounding the female meiocyte, suggesting a mobile signal rather than cell-autonomous control. AGO104 is necessary for non-CG methylation of centromeric and knob-repeat DNA. Digital gene expression tag profiling experiments using high-throughput sequencing show that AGO104 influences the transcription of many targets in the ovaries, with a strong effect on centromeric repeats. AGO104 is related to Arabidopsis thaliana AGO9, but while AGO9 acts to repress germ cell fate in somatic tissues, AGO104 acts to repress somatic fate in germ cells. Our findings show that female germ cell development in maize is dependent upon conserved small RNA pathways acting non-cell-autonomously in the ovule. Interfering with this repression leads to apomixis-like phenotypes in maize. PMID:21325139

RNF17 blocks promiscuous activity of PIWI proteins in mouse testes.

PubMed

Wasik, Kaja A; Tam, Oliver H; Knott, Simon R; Falciatori, Ilaria; Hammell, Molly; Vagin, Vasily V; Hannon, Gregory J

2015-07-01

PIWI proteins and their associated piRNAs protect germ cells from the activity of mobile genetic elements. Two classes of piRNAs—primary and secondary—are defined by their mechanisms of biogenesis. Primary piRNAs are processed directly from transcripts of piRNA cluster loci, whereas secondary piRNAs are generated in an adaptive amplification loop, termed the ping-pong cycle. In mammals, piRNA populations are dynamic, shifting as male germ cells develop. Embryonic piRNAs consist of both primary and secondary species and are mainly directed toward transposons. In meiotic cells, the piRNA population is transposon-poor and largely restricted to primary piRNAs derived from pachytene piRNA clusters. The transition from the embryonic to the adult piRNA pathway is not well understood. Here we show that RNF17 shapes adult meiotic piRNA content by suppressing the production of secondary piRNAs. In the absence of RNF17, ping-pong occurs inappropriately in meiotic cells. Ping-pong initiates piRNA responses against not only transposons but also protein-coding genes and long noncoding RNAs, including genes essential for germ cell development. Thus, the sterility of Rnf17 mutants may be a manifestation of a small RNA-based autoimmune reaction. © 2015 Wasik et al.; Published by Cold Spring Harbor Laboratory Press.

Co-chaperone Hsp70/Hsp90-organizing protein (Hop) is required for transposon silencing and Piwi-interacting RNA (piRNA) biogenesis.

PubMed

Karam, Joseph A; Parikh, Rasesh Y; Nayak, Dhananjaya; Rosenkranz, David; Gangaraju, Vamsi K

2017-04-14

Piwi-interacting RNAs (piRNAs) are 26-30-nucleotide germ line-specific small non-coding RNAs that have evolutionarily conserved function in mobile genetic element (transposons) silencing and maintenance of genome integrity. Drosophila Hsp70/90-organizing protein homolog (Hop), a co-chaperone, interacts with piRNA-binding protein Piwi and mediates silencing of phenotypic variations. However, it is not known whether Hop has a direct role in piRNA biogenesis and transposon silencing. Here, we show that knockdown of Hop in the germ line nurse cells (GLKD) of Drosophila ovaries leads to activation of transposons. Hop GLKD females can lay eggs at the same rate as wild-type counterparts, but the eggs do not hatch into larvae. Hop GLKD leads to the accumulation of γ-H2Av foci in the germ line, indicating increased DNA damage in the ovary. We also show that Hop GLKD-induced transposon up-regulation is due to inefficient piRNA biogenesis. Based on these results, we conclude that Hop is a critical component of the piRNA pathway and that it maintains genome integrity by silencing transposons. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

RNF17 blocks promiscuous activity of PIWI proteins in mouse testes

PubMed Central

Wasik, Kaja A.; Tam, Oliver H.; Knott, Simon R.; Falciatori, Ilaria; Hammell, Molly; Vagin, Vasily V.; Hannon, Gregory J.

2015-01-01

PIWI proteins and their associated piRNAs protect germ cells from the activity of mobile genetic elements. Two classes of piRNAs—primary and secondary—are defined by their mechanisms of biogenesis. Primary piRNAs are processed directly from transcripts of piRNA cluster loci, whereas secondary piRNAs are generated in an adaptive amplification loop, termed the ping-pong cycle. In mammals, piRNA populations are dynamic, shifting as male germ cells develop. Embryonic piRNAs consist of both primary and secondary species and are mainly directed toward transposons. In meiotic cells, the piRNA population is transposon-poor and largely restricted to primary piRNAs derived from pachytene piRNA clusters. The transition from the embryonic to the adult piRNA pathway is not well understood. Here we show that RNF17 shapes adult meiotic piRNA content by suppressing the production of secondary piRNAs. In the absence of RNF17, ping-pong occurs inappropriately in meiotic cells. Ping-pong initiates piRNA responses against not only transposons but also protein-coding genes and long noncoding RNAs, including genes essential for germ cell development. Thus, the sterility of Rnf17 mutants may be a manifestation of a small RNA-based autoimmune reaction. PMID:26115953

Surgery and Combination Chemotherapy in Treating Children With Extracranial Germ Cell Tumors

ClinicalTrials.gov

2017-12-07

Childhood Embryonal Tumor; Childhood Extracranial Germ Cell Tumor; Childhood Extragonadal Germ Cell Tumor; Childhood Malignant Ovarian Germ Cell Tumor; Childhood Malignant Testicular Germ Cell Tumor; Childhood Teratoma; Ovarian Embryonal Carcinoma; Ovarian Yolk Sac Tumor; Stage II Malignant Testicular Germ Cell Tumor; Stage IIA Ovarian Germ Cell Tumor; Stage IIB Ovarian Germ Cell Tumor; Stage IIC Ovarian Germ Cell Tumor; Stage III Malignant Testicular Germ Cell Tumor; Stage IIIA Ovarian Germ Cell Tumor; Stage IIIB Ovarian Germ Cell Tumor; Stage IIIC Ovarian Germ Cell Tumor; Testicular Choriocarcinoma and Yolk Sac Tumor; Testicular Embryonal Carcinoma

The evolving role of the orphan nuclear receptor ftz-f1, a pair-rule segmentation gene.

PubMed

Heffer, Alison; Grubbs, Nathaniel; Mahaffey, James; Pick, Leslie

2013-01-01

Segmentation is a critical developmental process that occurs by different mechanisms in diverse taxa. In insects, there are three common modes of embryogenesis-short-, intermediate-, and long-germ development-which differ in the number of segments specified at the blastoderm stage. While genes involved in segmentation have been extensively studied in the long-germ insect Drosophila melanogaster (Dm), it has been found that their expression and function in segmentation in short- and intermediate-germ insects often differ. Drosophila ftz-f1 encodes an orphan nuclear receptor that functions as a maternally expressed pair-rule segmentation gene, responsible for the formation of alternate body segments during Drosophila embryogenesis. Here we investigated the expression and function of ftz-f1 in the short-germ beetle, Tribolium castaneum (Tc). We found that Tc-ftz-f1 is expressed in stripes in Tribolium embryos. These stripes overlap alternate Tc-Engrailed (Tc-En) stripes, indicative of a pair-rule expression pattern. To test whether Tc-ftz-f1 has pair-rule function, we utilized embryonic RNAi, injecting double-stranded RNA corresponding to Tc-ftz-f1 coding or non-coding regions into early Tribolium embryos. Knockdown of Tc-ftz-f1 produced pair-rule segmentation defects, evidenced by loss of expression of alternate En stripes. In addition, a later role for Tc-ftz-f1 in cuticle formation was revealed. These results identify a new pair-rule gene in Tribolium and suggest that its role in segmentation may be shared among holometabolous insects. Interestingly, while Tc-ftz-f1 is expressed in pair-rule stripes, the gene is ubiquitously expressed in Drosophila embryos. Thus, the pair-rule function of ftz-f1 is conserved despite differences in expression patterns of ftz-f1 genes in different lineages. This suggests that ftz-f1 expression changed after the divergence of lineages leading to extant beetles and flies, likely due to differences in cis-regulatory sequences. We propose that the dependence of Dm-Ftz-F1 on interaction with the homeodomain protein Ftz which is expressed in stripes in Drosophila, loosened constraints on Dm-ftz-f1 expression, allowing for ubiquitous expression of this pair-rule gene in Drosophila. © 2013 Wiley Periodicals, Inc.

Accelerator experiments on the contribution of secondary particles to the production of cosmogenic nuclides in meteorites

NASA Technical Reports Server (NTRS)

Dragovitsch, P.; Englert, P.

1985-01-01

Through the interaction of galactic cosmic particle radiation (GCR) a wide variety of cosmogenic nuclides is produced in meteorites. They provide historical information about the cosmic radiation and the bombarded meteorites. An important way to understand the production mechanisms of cosmogenic nuclides in meteorites is to gather information about the depth and size dependence of the build-up of Galactic Rays Cosmic-secondary particles within meteorites of different sizes and chemical compositions. Simulation experiments with meteorite models offer an alternative to direct observation providing a data basis to describe the development and action of the secondary cascade induced by the GCR in meteorites.

Optimized shielding for space radiation protection

NASA Technical Reports Server (NTRS)

Wilson, J. W.; Cucinotta, F. A.; Kim, M. H.; Schimmerling, W.

2001-01-01

Future deep space mission and International Space Station exposures will be dominated by the high-charge and -energy (HZE) ions of the Galactic Cosmic Rays (GCR). A few mammalian systems have been extensively tested over a broad range of ion types and energies. For example, C3H10T1/2 cells, V79 cells, and Harderian gland tumors have been described by various track-structure dependent response models. The attenuation of GCR induced biological effects depends strongly on the biological endpoint, response model used, and material composition. Optimization of space shielding is then driven by the nature of the response model and the transmission characteristics of the given material.

Optimized Shielding for Space Radiation Protection

NASA Technical Reports Server (NTRS)

Wilson, J. W.; Cucinotta, F. A.; Kim, M.-H. Y.; Schimmerling, W.

2000-01-01

Abstract. Future deep space mission and International Space Station exposures will be dominated by the high-charge and -energy (HZE) ions of the Galactic Cosmic Rays (GCR). A few mammalian systems have been extensively tested over a broad range of ion types and energies. For example, C3H10T1/2 cells, V79 cells, and Harderian gland tumors have been described by various track-structure dependent response models. The attenuation of GCR induced biological effects depends strongly on the biological endpoint, response model used, and material composition. Optimization of space shielding is then driven by the nature of the response model and the transmission characteristics of the given material.

GCR-induced Photon Luminescence of the Moon: The Moon as a CR Detector

NASA Technical Reports Server (NTRS)

Wilson, Thomas L.; Lee, Kerry; Andersen, Vic

2007-01-01

We report on the results of a preliminary study of the GCR-induced photon luminescence of the Moon using the Monte Carlo program FLUKA. The model of the lunar surface is taken to be the chemical composition of soils found at various landing sites during the Apollo and Luna programs, averaged over all such sites to define a generic regolith for the present analysis. This then becomes the target that is bombarded by Galactic Cosmic Rays (GCRs) in FLUKA to determine the photon fluence when there is no sunshine or Earthshine. From the photon fluence we derive the energy spectrum which can be utilized to design an orbiting optical instrument for measuring the GCR-induced luminescence. This is to be distinguished from the gamma-ray spectrum produced by the radioactive decay of its radiogenic constituents lying in the surface and interior. Also, we investigate transient optical flashes from high-energy CRs impacting the lunar surface (boulders and regolith). The goal is to determine to what extent the Moon could be used as a rudimentary CR detector. Meteor impacts on the Moon have been observed for centuries to generate such flashes, so why not CRs?

Materials for Shielding Astronauts from the Hazards of Space Radiations

NASA Technical Reports Server (NTRS)

Wilson, J. W.; Cucinotta, F. A.; Miller, J.; Shinn, J. L.; Thibeault, S. A.; Singleterry, R. C.; Simonsen, L. C.; Kim, M. H.

1997-01-01

One major obstacle to human space exploration is the possible limitations imposed by the adverse effects of long-term exposure to the space environment. Even before human spaceflight began, the potentially brief exposure of astronauts to the very intense random solar energetic particle (SEP) events was of great concern. A new challenge appears in deep space exploration from exposure to the low-intensity heavy-ion flux of the galactic cosmic rays (GCR) since the missions are of long duration and the accumulated exposures can be high. Because cancer induction rates increase behind low to rather large thickness of aluminum shielding according to available biological data on mammalian exposures to GCR like ions, the shield requirements for a Mars mission are prohibitively expensive in terms of mission launch costs. Preliminary studies indicate that materials with high hydrogen content and low atomic number constituents are most efficient in protecting the astronauts. This occurs for two reasons: the hydrogen is efficient in breaking up the heavy GCR ions into smaller less damaging fragments and the light constituents produce few secondary radiations (especially few biologically damaging neutrons). An overview of the materials related issues and their impact on human space exploration will be given.

Designing Spacecraft and Mission Operations Plans to Meet Flight Crew Radiation Dose Requirements: Why is this an "Epic Challenge" for Long-Term Manned Interplanetary Flight

NASA Technical Reports Server (NTRS)

Koontz, Steven

2012-01-01

Outline of presentation: (1) Radiation Shielding Concepts and Performance - Galactic Cosmic Rays (GCRs) (1a) Some general considerations (1b) Galactic Cosmic Rays (2)GCR Shielding I: What material should I use and how much do I need? (2a) GCR shielding materials design and verification (2b) Spacecraft materials point dose cosmic ray shielding performance - hydrogen content and atomic number (2c) Accelerator point dose materials testing (2d) Material ranking and selection guidelines (2e) Development directions and return on investment (point dose metric) (2f) Secondary particle showers in the human body (2f-1) limited return of investment for low-Z, high-hydrogen content materials (3) GCR shielding II: How much will it cost? (3a) Spacecraft design and verification for mission radiation dose to the crew (3b) Habitat volume, shielding areal density, total weight, and launch cost for two habitat volumes (3c) It's All about the Money - Historical NASA budgets and budget limits (4) So, what can I do about all this? (4a) Program Design Architecture Trade Space (4b) The Vehicle Design Trade Space (4c) Some Near Term Recommendations

Galactic Cosmic Ray Intensity Response to Interplanetary Coronal Mass Ejections/Magnetic Clouds in 1995-2009

NASA Technical Reports Server (NTRS)

Richardson, I. G.; Cane, H. V.

2011-01-01

We summarize the response of the galactic cosmic ray (CGR) intensity to the passage of the more than 300 interplanetary coronal mass ejections (ICMEs) and their associated shocks that passed the Earth during 1995-2009, a period that encompasses the whole of Solar Cycle 23. In approx.80% of cases, the GCR intensity decreased during the passage of these structures, i.e., a "Forbush decrease" occurred, while in approx.10% there was no significant change. In the remaining cases, the GCR intensity increased. Where there was an intensity decrease, minimum intensity was observed inside the ICME in approx.90% of these events. The observations confirm the role of both post-shock regions and ICMEs in the generation of these decreases, consistent with many previous studies, but contrary to the conclusion of Reames, Kahler, and Tylka (Astrophys. 1. Lett. 700, L199, 2009) who, from examining a subset of ICMEs with flux-rope-like magnetic fields (magnetic clouds) argued that these are "open structures" that allow free access of particles including GCRs to their interior. In fact, we find that magnetic clouds are more likely to participate in the deepest GCR decreases than ICMEs that are not magnetic clouds.

Cosmogenic nuclides in the Martian surface: Constraints for sample recovery and transport

NASA Technical Reports Server (NTRS)

Englert, Peter A. J.

1988-01-01

Stable and radioactive cosmogenic nuclides and radiation damage effects such as cosmic ray tracks can provide information on the surface history of Mars. A recent overview on developments in cosmogenic nuclide research for historical studies of predominantly extraterrestrial materials was published previously. The information content of cosmogenic nuclides and radiation damage effects produced in the Martian surface is based on the different ways of interaction of the primary galactic and solar cosmic radiation (GCR, SCR) and the secondary particle cascade. Generally the kind and extent of interactions as seen in the products depend on the following factors: (1) composition, energy and intensity of the primary SCR and GCR; (2) composition, energy and intensity of the GCR-induced cascade of secondary particles; (3) the target geometry, i.e., the spatial parameters of Martian surface features with respect to the primary radiation source; (4) the target chemistry, i.e., the chemical composition of the Martian surface at the sampling location down to the minor element level or lower; and (5) duration of the exposure. These factors are not independent of each other and have a major influence on sample taking strategies and techniques.

Geological support for the Umbrella Effect as a link between geomagnetic field and climate

PubMed Central

Kitaba, Ikuko; Hyodo, Masayuki; Nakagawa, Takeshi; Katoh, Shigehiro; Dettman, David L.; Sato, Hiroshi

2017-01-01

The weakening of the geomagnetic field causes an increase in galactic cosmic ray (GCR) flux. Some researchers argue that enhanced GCR flux might lead to a climatic cooling by increasing low cloud formation, which enhances albedo (umbrella effect). Recent studies have reported geological evidence for a link between weakened geomagnetic field and climatic cooling. However, more work is needed on the mechanism of this link, including whether the umbrella effect is playing a central role. In this research, we present new geological evidence that GCR flux change had a greater impact on continental climate than on oceanic climate. According to pollen data from Osaka Bay, Japan, the decrease in temperature of the Siberian air mass was greater than that of the Pacific air mass during geomagnetic reversals in marine isotope stages (MIS) 19 and 31. Consequently, the summer land-ocean temperature gradient was smaller, and the summer monsoon was weaker. Greater terrestrial cooling indicates that a reduction of insolation is playing a key role in the link between the weakening of the geomagnetic field and climatic cooling. The most likely candidate for the mechanism seems to be the increased albedo of the umbrella effect. PMID:28091595

Geological support for the Umbrella Effect as a link between geomagnetic field and climate.

PubMed

Kitaba, Ikuko; Hyodo, Masayuki; Nakagawa, Takeshi; Katoh, Shigehiro; Dettman, David L; Sato, Hiroshi

2017-01-16

The weakening of the geomagnetic field causes an increase in galactic cosmic ray (GCR) flux. Some researchers argue that enhanced GCR flux might lead to a climatic cooling by increasing low cloud formation, which enhances albedo (umbrella effect). Recent studies have reported geological evidence for a link between weakened geomagnetic field and climatic cooling. However, more work is needed on the mechanism of this link, including whether the umbrella effect is playing a central role. In this research, we present new geological evidence that GCR flux change had a greater impact on continental climate than on oceanic climate. According to pollen data from Osaka Bay, Japan, the decrease in temperature of the Siberian air mass was greater than that of the Pacific air mass during geomagnetic reversals in marine isotope stages (MIS) 19 and 31. Consequently, the summer land-ocean temperature gradient was smaller, and the summer monsoon was weaker. Greater terrestrial cooling indicates that a reduction of insolation is playing a key role in the link between the weakening of the geomagnetic field and climatic cooling. The most likely candidate for the mechanism seems to be the increased albedo of the umbrella effect.

Role of Axumin PET Scan in Germ Cell Tumor

ClinicalTrials.gov

2018-05-01

Testis Cancer; Germ Cell Tumor; Testicular Cancer; Germ Cell Tumor of Testis; Germ Cell Tumor, Testicular, Childhood; Testicular Neoplasms; Testicular Germ Cell Tumor; Testicular Yolk Sac Tumor; Testicular Choriocarcinoma; Testicular Diseases; Germ Cell Cancer Metastatic; Germ Cell Neoplasm of Retroperitoneum; Germ Cell Cancer, Nos

Palifosfamide in Treating Patients With Recurrent Germ Cell Tumors

ClinicalTrials.gov

2015-06-11

Adult Central Nervous System Germ Cell Tumor; Adult Teratoma; Malignant Extragonadal Germ Cell Tumor; Malignant Extragonadal Non-Seminomatous Germ Cell Tumor; Extragonadal Seminoma; Recurrent Malignant Testicular Germ Cell Tumor; Recurrent Ovarian Germ Cell Tumor; Stage IV Extragonadal Non-Seminomatous Germ Cell Tumor; Stage IV Extragonadal Seminoma; Stage IV Ovarian Germ Cell Tumor

Case-control study of male germ cell tumors nested in a cohort of car-manufacturing workers: Findings from the occupational history.

PubMed

Langner, Ingo; Schmeisser, Nils; Mester, Birte; Behrens, Thomas; Gottlieb, Andrea; Ahrens, Wolfgang

2010-10-01

To examine whether the previously observed excess risk of male germ cell cancer in a cohort of car-manufacturing workers can be attributed to occupational activities inside and/or outside the car industry. A nested case-control study among workers in six plants included 205 cases of germ cell cancer and 1,105 controls, individually matched by year of birth (±2 years). Job periods of the individual occupational histories were coded based on the International Standard Classification of Occupations (ISCO) and the industrial classification of economic activities (NACE). Odds ratios (ORs) and corresponding 95%-confidence intervals (CI) for ever-never and cumulative employment were calculated by conditional multivariate logistic regression adjusted for cryptorchidism. Significantly increased risks were observed for machinery fitters and assemblers (A) (OR = 1.8, 95% CI 1.25-2.53) and "workers not elsewhere classified" (OR = 2.10, 95% CI 1.27-3.54), but no trend was observed for employment duration in either occupational group. Stratification of job group A by metal-cutting and non-cutting jobs yielded ORs of 1.87 (95% CI 1.31-2.67) and of 1.24 (95% CI 0.68-2.28), respectively. Among "plumbers, welders, sheet & structural metal workers" (adjusted OR 1.4, 95% CI 0.99-1.95) only "structural metal preparers and erectors" showed a substantially increased risk (OR = 2.30; 95% CI 1.27-4.27). Our results do not fully explain the increased incidence of germ cell cancer in the cohort, but support previous findings showing increased risks among metal workers. These risks were most strongly pronounced in metal-cutting activities. © 2010 Wiley-Liss, Inc.

Rare ATAD5 missense variants in breast and ovarian cancer patients.

PubMed

Maleva Kostovska, Ivana; Wang, Jing; Bogdanova, Natalia; Schürmann, Peter; Bhuju, Sabin; Geffers, Robert; Dürst, Matthias; Liebrich, Clemens; Klapdor, Rüdiger; Christiansen, Hans; Park-Simon, Tjoung-Won; Hillemanns, Peter; Plaseska-Karanfilska, Dijana; Dörk, Thilo

2016-06-28

ATAD5/ELG1 is a protein crucially involved in replication and maintenance of genome stability. ATAD5 has recently been identified as a genomic risk locus for both breast and ovarian cancer through genome-wide association studies. We aimed to investigate the spectrum of coding ATAD5 germ-line mutations in hospital-based series of patients with triple-negative breast cancer or serous ovarian cancer compared with healthy controls. The ATAD5 coding and adjacent splice site regions were analyzed by targeted next-generation sequencing of DNA samples from 273 cancer patients, including 114 patients with triple-negative breast cancer and 159 patients with serous epithelial ovarian cancer, and from 276 healthy females. Among 42 different variants identified, twenty-two were rare missense substitutions, of which 14 were classified as pathogenic by at least one in silico prediction tool. Three of four novel missense substitutions (p.S354I, p.H974R and p.K1466N) were predicted to be pathogenic and were all identified in ovarian cancer patients. Overall, rare missense variants with predicted pathogenicity tended to be enriched in ovarian cancer patients (14/159) versus controls (11/276) (p = 0.05, 2df). While truncating germ-line variants in ATAD5 were not detected, it remains possible that several rare missense variants contribute to genetic susceptibility toward epithelial ovarian carcinomas. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Galactic cosmic ray abundances and spectra behind defined shielding.

PubMed

Heinrich, W; Benton, E V; Wiegel, B; Zens, R; Rusch, G

1994-10-01

LET spectra have been measured for lunar missions and for several near Earth orbits ranging from 28 degrees to 83 degrees inclination. In some of the experiments the flux of GCR was determined separately from contributions caused by interactions in the detector material. Results of these experiments are compared to model calculations. The general agreement justifies the use of the model to calculate GCR fluxes. The magnitude of variations caused by solar modulation, geomagnetic shielding, and shielding by matter determined from calculated LET spectra is generally in agreement with experimental data. However, more detailed investigations show that there are some weak points in modeling solar modulation and shielding by material. These points are discussed in more detail.

IFN-beta1b augments glucocorticoid-induced suppression of tumor necrosis factor-alpha production by increasing the number of glucocorticoid receptors on a human monocytic cell line.

PubMed

Uitdehaag, B M; Hoekstra, K; Koper, J W; Polman, C H; Dijkstra, C D

2001-03-01

We studied the effect of recombinant interferon-beta1b (IFN-beta1b) on the sensitivity to glucocorticoids (GC) and on the number of GC receptors (GCR) in the human monocytic cell line THP-1. We found that IFN-beta1b augments the suppressive effect that dexamethasone has on the stimulated production of tumor necrosis factor-alpha (TNF-alpha), most likely related to the increased number of GCR observed after exposure to IFN-beta1b. This provides a possible clue to the mechanism of action of IFN-beta in multiple sclerosis.

Comparison of Model Calculations of Biological Damage from Exposure to Heavy Ions with Measurements

NASA Technical Reports Server (NTRS)

Kim, Myung-Hee Y.; Hada, Megumi; Cucinotta, Francis A.; Wu, Honglu

2014-01-01

The space environment consists of a varying field of radiation particles including high-energy ions, with spacecraft shielding material providing the major protection to astronauts from harmful exposure. Unlike low-LET gamma or X rays, the presence of shielding does not always reduce the radiation risks for energetic charged-particle exposure. Dose delivered by the charged particle increases sharply at the Bragg peak. However, the Bragg curve does not necessarily represent the biological damage along the particle path since biological effects are influenced by the track structures of both primary and secondary particles. Therefore, the ''biological Bragg curve'' is dependent on the energy and the type of the primary particle and may vary for different biological end points. Measurements of the induction of micronuclei (MN) have made across the Bragg curve in human fibroblasts exposed to energetic silicon and iron ions in vitro at two different energies, 300 MeV/nucleon and 1 GeV/nucleon. Although the data did not reveal an increased yield of MN at the location of the Bragg peak, the increased inhibition of cell progression, which is related to cell death, was found at the Bragg peak location. These results are compared to the calculations of biological damage using a stochastic Monte-Carlo track structure model, Galactic Cosmic Ray Event-based Risk Model (GERM) code (Cucinotta, et al., 2011). The GERM code estimates the basic physical properties along the passage of heavy ions in tissue and shielding materials, by which the experimental set-up can be interpreted. The code can also be used to describe the biophysical events of interest in radiobiology, cancer therapy, and space exploration. The calculation has shown that the severely damaged cells at the Bragg peak are more likely to go through reproductive death, the so called "overkill".

Partial purification, characterization and translation in vitro of rat liver metallothionein messenger ribonucleic acid.

PubMed Central

Andersen, R D; Weser, U

1978-01-01

Poly(A)+ (polyadenylated) mRNA coding for metallothioneins was purified 13-fold from rat liver polyribosomes and was identified by its ability to direct the biosynthesis of these proteins in a wheat-germ cell-free system. The carboxymethylated products of the protein-synthesizing system in vitro were analysed with sodium dodecyl sulphate/20% polyacrylamide-gel electrophoresis. The labelled compounds [3H]serine and [35S]cysteine were incorporated at high specific radioactivity into proteins that co-migrated with authentic metallothioneins. No [3H]leucine incorporation was found, in agreement with the amino acid composition of the metallothioneins. Metallothionein mRNA had a sedimentation coefficient of 9 S and carried a maximum of four ribosomes. At 5 h after a subcutaneous injection of ZnCl2 or CdCl2 (10 mumol/kg body wt.), the amount of this mRNA increased approx. 2- and 4-fold respectively, on the basis of translation in vitro. The increase in metallothionein mRNA (defined by translation in the wheat-germ system) was transient and, after CdCl2 treatment, fell back to control values by 17 h. Metallothioneins constituted a maximum of 0.8% of the total protein products synthesized in the wheat-germ system by total mRNA isolated from rat liver after CdCl2 treatment. Images Fig. 5. Fig. 6. PMID:743237

Elemental GCR Observations during the 2009-2010 Solar Minimum Period

NASA Technical Reports Server (NTRS)

Lave, K. A.; Israel, M. H.; Binns, W. R.; Christian, E. R.; Cummings, A. C.; Davis, A. J.; deNolfo, G. A.; Leske, R. A.; Mewaldt, R. A.; Stone, E. C.;

A Monte Carlo-based radiation safety assessment for astronauts in an environment with confined magnetic field shielding.

PubMed

Geng, Changran; Tang, Xiaobin; Gong, Chunhui; Guan, Fada; Johns, Jesse; Shu, Diyun; Chen, Da

2015-12-01

The active shielding technique has great potential for radiation protection in space exploration because it has the advantage of a significant mass saving compared with the passive shielding technique. This paper demonstrates a Monte Carlo-based approach to evaluating the shielding effectiveness of the active shielding technique using confined magnetic fields (CMFs). The International Commission on Radiological Protection reference anthropomorphic phantom, as well as the toroidal CMF, was modeled using the Monte Carlo toolkit Geant4. The penetrating primary particle fluence, organ-specific dose equivalent, and male effective dose were calculated for particles in galactic cosmic radiation (GCR) and solar particle events (SPEs). Results show that the SPE protons can be easily shielded against, even almost completely deflected, by the toroidal magnetic field. GCR particles can also be more effectively shielded against by increasing the magnetic field strength. Our results also show that the introduction of a structural Al wall in the CMF did not provide additional shielding for GCR; in fact it can weaken the total shielding effect of the CMF. This study demonstrated the feasibility of accurately determining the radiation field inside the environment and evaluating the organ dose equivalents for astronauts under active shielding using the CMF.

A temporal forecast of radiation environments for future space exploration missions.

PubMed

Kim, Myung-Hee Y; Cucinotta, Francis A; Wilson, John W

2007-06-01

The understanding of future space radiation environments is an important goal for space mission operations, design, and risk assessment. We have developed a solar cycle statistical model in which sunspot number is coupled to space-related quantities, such as the galactic cosmic radiation (GCR) deceleration potential (phi) and the mean occurrence frequency of solar particle events (SPEs). Future GCR fluxes were derived from a predictive model, in which the temporal dependence represented by phi was derived from GCR flux and ground-based Climax neutron monitor rate measurements over the last four decades. These results showed that the point dose equivalent inside a typical spacecraft in interplanetary space was influenced by solar modulation by up to a factor of three. It also has been shown that a strong relationship exists between large SPE occurrences and phi. For future space exploration missions, cumulative probabilities of SPEs at various integral fluence levels during short-period missions were defined using a database of proton fluences of past SPEs. Analytic energy spectra of SPEs at different ranks of the integral fluences for energies greater than 30 MeV were constructed over broad energy ranges extending out to GeV for the analysis of representative exposure levels at those fluences. Results will guide the design of protection systems for astronauts during future space exploration missions.

Transient IP Structures Associated with Short-Period Variations in the Solar Energetic Particle and Galactic Cosmic Ray Flux

NASA Astrophysics Data System (ADS)

Mulligan, T.; Blake, J.; Spence, H. E.; Jordan, A. P.; Quenby, J. J.; Shaul, D.

2006-12-01

Short-period variations in the integral SEP ( > 10 MeV) and GCR fluence ( > 100 MeV), often observed in neutron monitor data have also been seen by the High Sensitivity Telescope (HIST) aboard the Polar Spacecraft. Although HIST was designed to measure radiation-belt electrons, it makes clean measurements of the integral SEP and GCR fluence when Polar is outside the radiation belts. These measurements show variability on a variety of timescales including 0.1~mHz - 1~mHz. We examine these variations from Polar and compare them with IMF and plasma solar wind conditions at L1 using ACE data. We find coherent short-term variability occurs when Earth is in close proximity to the HCS and when Earth is either inside an ICME or when an ICME has just transited the Earth. Also, when a flux rope ICME signature is present, the rope axis is nearly parallel to the radial direction and the HCS. The launch of STEREO will enable detailed 3-D analyses of such solar wind disturbances along spatial scales on the same order of typical SEP and GCR proton gyroradii, which are needed to elucidate the mechanism behind this short-period variability.

Simulation of the GCR spectrum in the Mars curiosity rover's RAD detector using MCNP6.

PubMed

Ratliff, Hunter N; Smith, Michael B R; Heilbronn, Lawrence

2017-08-01

The paper presents results from MCNP6 simulations of galactic cosmic ray (GCR) propagation down through the Martian atmosphere to the surface and comparison with RAD measurements made there. This effort is part of a collaborative modeling workshop for space radiation hosted by Southwest Research Institute (SwRI). All modeling teams were tasked with simulating the galactic cosmic ray (GCR) spectrum through the Martian atmosphere and the Radiation Assessment Detector (RAD) on-board the Curiosity rover. The detector had two separate particle acceptance angles, 4π and 30 ° off zenith. All ions with Z = 1 through Z = 28 were tracked in both scenarios while some additional secondary particles were only tracked in the 4π cases. The MCNP6 4π absorbed dose rate was 307.3 ± 1.3 µGy/day while RAD measured 233 µGy/day. Using the ICRP-60 dose equivalent conversion factors built into MCNP6, the simulated 4π dose equivalent rate was found to be 473.1 ± 2.4 µSv/day while RAD reported 710 µSv/day. Copyright © 2017 The Committee on Space Research (COSPAR). Published by Elsevier Ltd. All rights reserved.

Effects of Nuclear Cross Sections at Different Energies on Space Radiation Exposure from Galactic Cosmic Rays

NASA Technical Reports Server (NTRS)

Li, Zi-Wei; Adams, James H., Jr.

2007-01-01

Space radiation from galactic cosmic rays (GCR) is a major hazard to space crews, especially in long duration human space explorations. For this reason, they will be protected by radiation shielding that fragments the GCR heavy ions. Here we investigate how sensitive the crew's radiation exposure is to nuclear fragmentation cross sections at different energies. We find that in deep space cross sections between about 0.2 and 1.2 GeV/u have the strongest effect on dose equivalent behind shielding in solar minimum GCR environments, and cross sections between about 0.6 and 1.7 GeV/u are the most important at solar maximum'. On the other hand, at the location of the International Space Station, cross sections at_higher -energies, between about 0.6 and 1.7 GeV /u at solar minimum and between about 1.7 and 3.4 GeV/u'at,solar maximum, are the most important This is. due-to the average geomagnetic cutoff for the ISS orbit. We also show the effect of uncertainties in the fragmentation cross sections on the elemental energy spectra behind shielding. These results help to focus the studies of fragmentation cross sections on the proper energy range in order to improve our predictions of crew exposures.

A paternal environmental legacy: evidence for epigenetic inheritance through the male germ line.

PubMed

Soubry, Adelheid; Hoyo, Cathrine; Jirtle, Randy L; Murphy, Susan K

2014-04-01

Literature on maternal exposures and the risk of epigenetic changes or diseases in the offspring is growing. Paternal contributions are often not considered. However, some animal and epidemiologic studies on various contaminants, nutrition, and lifestyle-related conditions suggest a paternal influence on the offspring's future health. The phenotypic outcomes may have been attributed to DNA damage or mutations, but increasing evidence shows that the inheritance of environmentally induced functional changes of the genome, and related disorders, are (also) driven by epigenetic components. In this essay we suggest the existence of epigenetic windows of susceptibility to environmental insults during sperm development. Changes in DNA methylation, histone modification, and non-coding RNAs are viable mechanistic candidates for a non-genetic transfer of paternal environmental information, from maturing germ cell to zygote. Inclusion of paternal factors in future research will ultimately improve the understanding of transgenerational epigenetic plasticity and health-related effects in future generations. © 2014 The Authors. Bioessays published by WILEY Periodicals, Inc.

Polymeric Materials With Additives for Durability and Radiation Shielding in Space

NASA Technical Reports Server (NTRS)

Kiefer, Richard

2011-01-01

Polymeric materials are attractive for use in space structures because of their light weight and high strength In addition, polymers are made of elements with low atomic numbers (Z), primarily carbon (C), hydrogen (H), oxygen (0), and nitrogen (N) which provide the best shielding from galactic cosmic rays (GCR) (ref. 1). Galactic cosmic rays are composed primarily of nuclei (i.e., fully ionized atoms) plus a contribution of about 2% from electrons and positrons. There is a small but significant component of GCR particles with high charge (Z > 10) and high energy (E >100 GeV) (ref. 2). These so-called HZE particles comprise only 1 to 2% of the cosmic ray fluence but they interact with very high specific ionization and contribute 50% of the long- term dose to humans. The best shield for this radiation would be liquid hydrogen, which is not feasible. For this reason, hydrogen-containing polymers make the most effective practical shields. Moreover, neutrons are formed in the interactions of GCR particles with materials. Neutrons can only lose energy by collisions or reactions with a nucleus since they are uncharged. This is a process that is much less probable than the Coulombic interactions of charged particles. Thus, neutrons migrate far from the site of the reaction in which they were formed. This increases the probability of neutrons reaching humans or electronic equipment. Fast neutrons (> 1 MeV) can interact with silicon chips in electronic equipment resulting in the production of recoil ions which can cause single event upsets (SEU) in sensitive components (ref. 3). Neutrons lose energy most effectively by elastic collisions with light atoms, particularly hydrogen atoms. Therefore, hydrogen-containing polymers are not only effective in interacting with GCR particles; they are also effective in reducing the energy of the neutrons formed in the interactions.

Sunspot activity and cosmic ray modulation at 1 a.u. for 1900-2013

NASA Astrophysics Data System (ADS)

Ahluwalia, H. S.

2014-10-01

The descent of sunspot cycle 23 to an unprecedented minimum of long duration in 2006-2009 led to a prolonged galactic cosmic ray (GCR) recovery to the highest level observed in the instrumental era for a variety of energetic charged particle species on Earth, over a wide range of rigidities. The remarkable GCR increase measured by several ground-based, balloon-borne, and detectors on a satellite is described and discussed. It is accompanied by a decrease in solar wind velocity and interplanetary magnetic field at 1 a.u., reaching the lowest values since measurements of the solar wind began in October 1963; the solar polar field strength (μT) measured at the Wilcox Solar Observatory (WSO) is also significantly reduced compared to prior cycles since the start of the program in 1976, the polar field in the northern hemisphere reversed in June 2012 and again in February 2014, that in the southern hemisphere reversed in July 2013. If updates of WSO data confirm the second reversal in northern solar hemisphere, it would pose a serious challenge to the Dynamo Theory. The long-term change in solar behavior may have begun in 1992, perhaps earlier. The physical underpinnings of these solar changes need to be understood and their effect on GCR modulation processes clarified. The study discusses the recent phenomena in the context of GCR modulation since 1900. These happenings affected our empirical predictions for the key parameters for the next two sunspot cycles (they may be progressively less active than sunspot cycle 24) but it enhanced support for our prediction that solar activity is descending into a Dalton-like grand minimum in the middle of the twentyfirst century, reducing the frequency of the coronal mass ejections; they determine the space weather affecting the quality of life on Earth, radiation dose for hardware and human activities in space as well as the frequency of large Forbush decreases at 1 a.u.

Radiation Transport Properties of Potential In Situ-Developed Regolith-Epoxy Materials for Martian Habitats

NASA Technical Reports Server (NTRS)

Miller, Jack; Heilbronn, Lawrence H.; Zeitlin, Cary J.; Wilson, John W.; Singleterry, Robert C., Jr.; Thibeault, Sheila Ann

2003-01-01

Mission crews in space outside the Earth s magnetic field will be exposed to high energy heavy charged particles in the galactic cosmic radiation (GCR). These highly ionizing particles will be a source of radiation risk to crews on extended missions to the Moon and Mars, and the biological effects of and countermeasures to the GCR have to be investigated as part of the planning of exploration-class missions. While it is impractical to shield spacecraft and planetary habitats against the entire GCR spectrum, biological and physical studies indicate that relatively modest amounts of shielding are effective at reducing the radiation dose. However, nuclear fragmentation in the shielding materials produces highly penetrating secondary particles, which complicates the problem: in some cases, some shielding is worse than none at all. Therefore the radiation transport properties of potential shielding materials need to be carefully investigated. One intriguing option for a Mars mission is the use of material from the Martian surface, in combination with chemicals carried from Earth and/or fabricated from elements found in the Martian atmosphere, to construct crew habitats. We have measured the transmission properties of epoxy-Martian regolith composites with respect to heavy charged particles characteristic of the GCR ions which bombard the Martian surface. The composites were prepared at NASA Langley Research Center using simulated Martian regolith, in the process also evaluating fabrication methods which could lead to technologies for in situ fabrication on Mars. Initial evaluation of the radiation shielding properties is made using radiation transport models developed at NASA-LaRC, and the results of these calculations are used to select the composites with the most favorable radiation transmission properties. These candidates are then evaluated at particle accelerators which produce beams of heavy charged particles representative in energy and charge of the radiation at the surface of Mars. The ultimate objective is to develop the models into a design tool for use by mission planners, flight surgeons and radiation health specialists.

Forbush Decrease events in Lunar Radiation Environment observed by the LRO/CRaTER

NASA Astrophysics Data System (ADS)

Sohn, J.; Oh, S.; Yi, Y.; Kim, E.; Lee, J.; Spence, H. E.

2012-12-01

The Lunar Reconnaissance Orbiter (LRO) launched on June 16, 2009 has six experiments including of the Cosmic Ray Telescope for the Effects of Radiation (CRaTER) onboard. The CRaTER instrument characterizes the radiation environment to be experienced by humans during future lunar missions. The CRaTER instrument measures the effects of ionizing energy loss in matter specifically in silicon solid-state detectors due to penetrating solar energetic protons (SEP) and galactic cosmic rays (GCR) after interactions with tissue-equivalent plastic (TEP), a synthetic analog of human tissue. The CRaTER instrument houses a compact and highly precise microdosimeter. It measures dose rates below one micro-Rad/sec in lunar radiation environment. Forbush decrease (FD) event is the sudden decrease of galactic cosmic ray (GCR) flux. The FD event is considered to be caused by exclusion of GCR due to intense interplanetary magnetic field (IMF) structures of interplanetary shock (IP) sheath region and/or the interplanetary coronal mass ejection (CME) following the IP shocks as a shock driver. We use the data of cosmic ray flux and dose rates observed by the CRaTER instrument. We also use the CME list of STEREO SECCHI inner, outer coronagraph and the IMF (Interplanetary CME) data of the ACE/MAG instrument. We examine the origins and the characteristics of the FD-like events in lunar radiation environment. We also compare these events with the FD events on the Earth. We find that whenever the FD events are recorded at ground Neutron Monitor stations, the FD-like events also occur on the lunar environments. The flux variation amplitude of FD-like events on the Moon is approximately two times larger than that of FD events on the Earth. We compare time profiles of GCR flux with of the dose rate of FD-like events in the lunar environment. We figure out that the distinct FD-like events correspond to dose rate events in the CRaTER on lunar environment during the event period.

Alvocidib and Oxaliplatin With or Without Fluorouracil and Leucovorin Calcium in Treating Patients With Relapsed or Refractory Germ Cell Tumors

ClinicalTrials.gov

2017-01-20

Recurrent Extragonadal Seminoma; Recurrent Malignant Extragonadal Germ Cell Tumor; Recurrent Malignant Extragonadal Non-Seminomatous Germ Cell Tumor; Recurrent Malignant Testicular Germ Cell Tumor; Recurrent Ovarian Germ Cell Tumor; Stage III Testicular Cancer; Stage IV Extragonadal Non-Seminomatous Germ Cell Tumor; Stage IV Extragonadal Seminoma; Stage IV Ovarian Germ Cell Tumor

Combination Chemotherapy in Treating Young Patients With Recurrent or Resistant Malignant Germ Cell Tumors

ClinicalTrials.gov

2017-11-14

Childhood Extracranial Germ Cell Tumor; Childhood Extragonadal Germ Cell Tumor; Childhood Malignant Ovarian Germ Cell Tumor; Childhood Malignant Testicular Germ Cell Tumor; Ovarian Choriocarcinoma; Ovarian Embryonal Carcinoma; Ovarian Yolk Sac Tumor; Recurrent Childhood Malignant Germ Cell Tumor; Recurrent Malignant Testicular Germ Cell Tumor; Recurrent Ovarian Germ Cell Tumor; Testicular Choriocarcinoma; Testicular Choriocarcinoma and Embryonal Carcinoma; Testicular Choriocarcinoma and Yolk Sac Tumor; Testicular Embryonal Carcinoma; Testicular Embryonal Carcinoma and Yolk Sac Tumor; Testicular Yolk Sac Tumor

Lipid phosphate phosphatase activity regulates dispersal and bilateral sorting of embryonic germ cells in Drosophila

PubMed Central

Renault, Andrew D.; Kunwar, Prabhat S.; Lehmann, Ruth

2010-01-01

In Drosophila, germ cell survival and directionality of migration are controlled by two lipid phosphate phosphatases (LPP), wunen (wun) and wunen-2 (wun2). wun wun2 double mutant analysis reveals that the two genes, hereafter collectively called wunens, act redundantly in primordial germ cells. We find that wunens mediate germ cell-germ cell repulsion and that this repulsion is necessary for germ cell dispersal and proper transepithelial migration at the onset of migration and for the equal sorting of the germ cells between the two embryonic gonads during their migration. We propose that this dispersal function optimizes adult fecundity by assuring maximal germ cell occupancy of both gonads. Furthermore, we find that the requirement for wunens in germ cell survival can be eliminated by blocking germ cell migration. We suggest that this essential function of Wunen is needed to maintain cell integrity in actively migrating germ cells. PMID:20431117

Space Radiation and Exploration - Information for the Augustine Committee Review

NASA Technical Reports Server (NTRS)

Cucinotta, Francis; Semones, Edward; Kim, Myung-Hee; Jackson, Lori

2009-01-01

Space radiation presents significant health risks including mortality for Exploration missions: a) Galactic cosmic ray (GCR) heavy ions are distinct from radiation that occurs on Earth leading to different biological impacts. b) Large uncertainties in GCR risk projections impact ability to design and assess mitigation approaches and select crew. c) Solar Proton Events (SPEs) require new operational and shielding approaches and new biological data on risks. Risk estimates are changing as new scientific knowledge is gained: a) Research on biological effects of space radiation show qualitative and quantitative differences with X- or gamma-rays. b) Expert recommendations and regulatory policy are changing. c) New knowledge leads to changes in estimates for the number of days in space to stay below Permissible Exposure Limits (PELS).

Radiation Physics for Space and High Altitude Air Travel

NASA Technical Reports Server (NTRS)

Cucinotta, F. A.; Wilson, J. W.; Goldhagen, P.; Saganti, P.; Shavers, M. R.; McKay, Gordon A. (Technical Monitor)

2000-01-01

Galactic cosmic rays (GCR) are of extra-solar origin consisting of high-energy hydrogen, helium, and heavy ions. The GCR are modified by physical processes as they traverse through the solar system, spacecraft shielding, atmospheres, and tissues producing copious amounts of secondary radiation including fragmentation products, neutrons, mesons, and muons. We discuss physical models and measurements relevant for estimating biological risks in space and high-altitude air travel. Ambient and internal spacecraft computational models for the International Space Station and a Mars mission are discussed. Risk assessment is traditionally based on linear addition of components. We discuss alternative models that include stochastic treatments of columnar damage by heavy ion tracks and multi-cellular damage following nuclear fragmentation in tissue.

Twenty years of space radiation physics at the BNL AGS and NASA Space Radiation Laboratory.

PubMed

Miller, J; Zeitlin, C

2016-06-01

Highly ionizing atomic nuclei HZE in the GCR will be a significant source of radiation exposure for humans on extended missions outside low Earth orbit. Accelerators such as the LBNL Bevalac and the BNL AGS, designed decades ago for fundamental nuclear and particle physics research, subsequently found use as sources of GCR-like particles for ground-based physics and biology research relevant to space flight. The NASA Space Radiation Laboratory at BNL was constructed specifically for space radiation research. Here we review some of the space-related physics results obtained over the first 20 years of NASA-sponsored research at Brookhaven. Copyright © 2016 The Committee on Space Research (COSPAR). Published by Elsevier Ltd. All rights reserved.

Exploring the Excluded Galactic Cosmic Rays--those at the Lowest Energies.

NASA Astrophysics Data System (ADS)

Shapiro, Maurice M.

2001-04-01

The solar wind prevents the lowest- energy Galactic cosmic rays (GCR) from entering the heliosphere. Consequently, space probes have thus far been unable to sample them. We suggest that astrochemistry may provide a ``handle" on these particles. Clouds in the interstellar medium (ISM) are sites of chemical-reaction networks that produce various molecular species detectable by their radioastronomical signatures. Highly ionizing low-energy cosmic rays are thought to be the principal agents of molecule production in clouds. Some anomalous abundances, e.g., of deuterium molecules, have been detected. Could studies of the foregoing networks of reactions and their products yield clues to the fluxes and energy spectra of the lowest-energy GCR in the ISM? Other approaches to this problem are also cited.

Exploring the Galactic Cosmic Rays at the lowest energies

NASA Astrophysics Data System (ADS)

Shapiro, M. M.

2001-08-01

The solar wind prevents the lowest-energy Galactic cosmic rays (GCR) from entering the Heliosphere. Consequently, space probes have thus far been unable to sample them. We suggest that astrochemistry may provide a handle on these particles. Clouds in the interstellar medium (ISM) are sites of chemical-reaction networks that produce various molecular species detectable by their radioastronomical signatures. Highly ionizing low-energy cosmic rays are thought to be the principal agents of molecule production in clouds. Some anomalous abundances, e.g., of deuterium molecules, have been detected. Could studies of the foregoing networks of reactions and their products yield clues to the fluxes and energy spectra of the lowest-energy GCR in the ISM? Other approaches to this problem are also cited.

Intermolecular Interactions of Homologs of Germ Plasm Components in Mammalian Germ Cells

PubMed Central

Fox, Mark S.; Clark, Amander T.; El Majdoubi, Mohammed; Vigne, Jean-Louis; Urano, Jun; Hostetler, Chris E.; Griswold, Michael D.; Weiner, Richard I.; Pera, Renee A. Reijo

2007-01-01

In some species such as flies, worms, frogs, and fish the key to forming and maintaining early germ cell populations is the assembly of germ plasm, microscopically-distinct egg cytoplasm that is rich in RNAs, RNA-binding proteins and ribosomes. Cells which inherit germ plasm are destined for the germ cell lineage. In contrast, in mammals, germ cells are formed and maintained later in development as a result of inductive signaling from one embryonic cell type to another. Research advances, using complementary approaches, including identification of key signaling factors that act during the initial stages of germ cell development, differentiation of germ cells in vitro from mouse and human embryonic stem cells and the demonstration, that homologs of germ plasm components are conserved in mammals, have shed light on key elements in the early development of mammalian germ cells. Here, we use FRET (Fluorescence Resonance Energy Transfer) to demonstrate that living mammalian germ cells possess specific RNA/protein complexes that contain germ plasm homologs, beginning in the earliest stages of development examined. Moreover, we demonstrate that although both human and mouse germ cells and embryonic stem cells express the same proteins, germ cell specific protein/protein interactions distinguish germ cells from precursor embryonic stem cells in vitro; interactions also determine sub-cellular localization of complex components. Finally, we suggest that assembly of similar protein complexes may be central to differentiation of diverse cell lineages and provide useful diagnostic tools for isolation of specific cell types from the assorted types differentiated from embryonic stem cells. PMID:16996493

GERMcode: A Stochastic Model for Space Radiation Risk Assessment

NASA Technical Reports Server (NTRS)

Kim, Myung-Hee Y.; Ponomarev, Artem L.; Cucinotta, Francis A.

2012-01-01

A new computer model, the GCR Event-based Risk Model code (GERMcode), was developed to describe biophysical events from high-energy protons and high charge and energy (HZE) particles that have been studied at the NASA Space Radiation Laboratory (NSRL) for the purpose of simulating space radiation biological effects. In the GERMcode, the biophysical description of the passage of HZE particles in tissue and shielding materials is made with a stochastic approach that includes both particle track structure and nuclear interactions. The GERMcode accounts for the major nuclear interaction processes of importance for describing heavy ion beams, including nuclear fragmentation, elastic scattering, and knockout-cascade processes by using the quantum multiple scattering fragmentation (QMSFRG) model. The QMSFRG model has been shown to be in excellent agreement with available experimental data for nuclear fragmentation cross sections. For NSRL applications, the GERMcode evaluates a set of biophysical properties, such as the Poisson distribution of particles or delta-ray hits for a given cellular area and particle dose, the radial dose on tissue, and the frequency distribution of energy deposition in a DNA volume. By utilizing the ProE/Fishbowl ray-tracing analysis, the GERMcode will be used as a bi-directional radiation transport model for future spacecraft shielding analysis in support of Mars mission risk assessments. Recent radiobiological experiments suggest the need for new approaches to risk assessment that include time-dependent biological events due to the signaling times for activation and relaxation of biological processes in cells and tissue. Thus, the tracking of the temporal and spatial distribution of events in tissue is a major goal of the GERMcode in support of the simulation of biological processes important in GCR risk assessments. In order to validate our approach, basic radiobiological responses such as cell survival curves, mutation, chromosomal aberrations, and representative mouse tumor induction curves are implemented into the GERMcode. Extension of these descriptions to other endpoints related to non-targeted effects and biochemical pathway responses will be discussed.

Prediction of the solar modulation of galactic cosmic rays and radiation dose of aircrews up to the solar cycle 26

NASA Astrophysics Data System (ADS)

Miyake, S.; Kataoka, R.; Sato, T.

2016-12-01

The solar modulation of galactic cosmic rays (GCRs), which is the variation of the terrestrial GCR flux caused by the heliospheric environmental change, is basically anti-correlated with the solar activity with so-called 11-year periodicity. In the current weak solar cycle 24, we expect that the flux of GCRs is getting higher than that in the previous solar cycles, leading to the increase in the radiation exposure in the space and atmosphere. In order to quantitatively evaluate the possible solar modulation of GCRs and resultant radiation exposure at flight altitude during the solar cycles 24, 25, and 26, we have developed the time-dependent and three-dimensional model of the solar modulation of GCRs. Our model can give the flux of GCRs anywhere in the heliosphere by assuming the variation of the solar wind velocity, the strength of the interplanetary magnetic field, and its tilt angle. We solve the curvature and gradient drift motion of GCRs in the heliospheric magnetic field, and therefore reproduce the 22-year variation of the solar modulation of GCRs. It is quantitatively confirmed that our model reproduces the energy spectra observed by BESS and PAMELA. We then calculate the variation of the GCR energy spectra during the solar cycles 24, 25, and 26, by extrapolating the solar wind parameters and tilt angle. We also calculate the neutron monitor counting rate and the radiation dose of aircrews at flight altitude, by the air-shower simulation performed by PHITS (Particle and Heavy Ion Transport code System). In this presentation, we report the quantitative forecast values of the solar modulation of GCRs, neutron monitor counting rate, and the radiation dose at flight altitude up to the cycle 26, including the discussion of the charge sign dependence on those results.

Proton flux and radiation dose from galactic cosmic rays in the lunar regolith and implications for organic synthesis at the poles of the Moon and Mercury

NASA Astrophysics Data System (ADS)

Crites, S. T.; Lucey, P. G.; Lawrence, D. J.

2013-11-01

Galactic cosmic rays are a potential energy source to stimulate organic synthesis from simple ices. The recent detection of organic molecules at the polar regions of the Moon by LCROSS (Colaprete, A. et al. [2010]. Science 330, 463-468, http://dx.doi.org/10.1126/science.1186986), and possibly at the poles of Mercury (Paige, D.A. et al. [2013]. Science 339, 300-303, http://dx.doi.org/10.1126/science.1231106), introduces the question of whether the organics were delivered by impact or formed in situ. Laboratory experiments show that high energy particles can cause organic production from simple ices. We use a Monte Carlo particle scattering code (MCNPX) to model and report the flux of GCR protons at the surface of the Moon and report radiation dose rates and absorbed doses at the Moon’s surface and with depth as a result of GCR protons and secondary particles, and apply scaling factors to account for contributions to dose from heavier ions. We compare our results with dose rate measurements by the Cosmic Ray Telescope for the Effects of Radiation (CRaTER) experiment on Lunar Reconnaissance Orbiter (Schwadron, N.A. et al. [2012]. J. Geophys. Res. 117, E00H13, http://dx.doi.org/10.1029/2011JE003978) and find them in good agreement, indicating that MCNPX can be confidently applied to studies of radiation dose at and within the surface of the Moon. We use our dose rate calculations to conclude that organic synthesis is plausible well within the age of the lunar polar cold traps, and that organics detected at the poles of the Moon may have been produced in situ. Our dose rate calculations also indicate that galactic cosmic rays can induce organic synthesis within the estimated age of the dark deposits at the pole of Mercury that may contain organics.

Comparison of Martian Surface Radiation Predictions to the Measurements of Mars Science Laboratory Radiation Assessment Detector (MSL/RAD)

NASA Technical Reports Server (NTRS)

Kim, Myung-Hee Y.; Cucinotta, Francis A.; Zeitlin, Cary; Hassler, Donald M.; Ehresmann, Bent; Rafkin, Scot C. R.; Wimmer-Schweingruber, Robert F; Boettcher, Stephan; Boehm, Eckart; Guo, Jingnan;

Characterization of the particle radiation environment at three potential landing sites on Mars using ESA’s MEREM models

NASA Astrophysics Data System (ADS)

McKenna-Lawlor, S.; Gonçalves, P.; Keating, A.; Morgado, B.; Heynderickx, D.; Nieminen, P.; Santin, G.; Truscott, P.; Lei, F.; Foing, B.; Balaz, J.

2012-03-01

The ‘Mars Energetic Radiation Environment Models’ (dMEREM and eMEREM) recently developed for the European Space Agency are herein used to estimate, for the first time, background Galactic Cosmic Ray (GCR) radiation and flare related solar energetic particle (SEP) events at three candidate martian landing sites under conditions where particle arrival occurred at solar minimum (December, 2006) and solar maximum (April, 2002) during Solar Cycle 23. The three landing sites were selected on the basis that they are characterized by significantly different hydrological conditions and soil compositions. Energetic particle data sets recorded on orbit at Mars at the relevant times were incomplete because of gaps in the measurements due to operational constraints. Thus, in the present study, comprehensive near-Earth particle measurements made aboard the GOES spacecraft were used as proxies to estimate the overall particle doses at each perspective landing site, assuming in each case that the fluxes fell off as 1/r2 (where r is the helio-radial distance) and that good magnetic connectivity always prevailed. The results indicate that the particle radiation environment on Mars can vary according to the epoch concerned and the landing site selected. Particle estimations obtained using MEREM are in reasonable agreement, given the inherent differences between the models, with the related NASA Heavy Ion-Nucleon Transport Code for Space Radiation/HZETRN. Both sets of results indicated that, for short (30 days) stays, the atmosphere of Mars, in the cases of the SEPs studied and the then prevailing background galactic cosmic radiation, provided sufficient shielding at the planetary surface to maintain annual skin and blood forming organ/BFO dose levels below currently accepted ionizing radiation exposure limits. The threat of occurrence of a hard spectrum SEP during Cruise-Phase transfers to/from Mars over 400 days, combined with the associated cumulative effect of prolonged GCR exposure, poses an as yet unsolved hazard to prospective onboard personnel.

Imatinib Mesylate in Treating Patients With Progressive, Refractory, or Recurrent Stage II or Stage III Testicular or Ovarian Cancer

ClinicalTrials.gov

2013-01-15

Ovarian Dysgerminoma; Recurrent Malignant Testicular Germ Cell Tumor; Recurrent Ovarian Germ Cell Tumor; Stage II Malignant Testicular Germ Cell Tumor; Stage II Ovarian Germ Cell Tumor; Stage III Malignant Testicular Germ Cell Tumor; Stage III Ovarian Germ Cell Tumor; Testicular Seminoma

Role of maternal Xenopus syntabulin in germ plasm aggregation and primordial germ cell specification.

PubMed

Oh, Denise; Houston, Douglas W

2017-12-15

The localization and organization of mitochondria- and ribonucleoprotein granule-rich germ plasm is essential for many aspects of germ cell development. In Xenopus, germ plasm is maternally inherited and is required for the specification of primordial germ cells (PGCs). Germ plasm is aggregated into larger patches during egg activation and cleavage and is ultimately translocated perinuclearly during gastrulation. Although microtubule dynamics and a kinesin (Kif4a) have been implicated in Xenopus germ plasm localization, little is known about how germ plasm distribution is regulated. Here, we identify a role for maternal Xenopus Syntabulin in the aggregation of germ plasm following fertilization. We show that depletion of sybu mRNA using antisense oligonucleotides injected into oocytes results in defects in the aggregation and perinuclear transport of germ plasm and subsequently in reduced PGC numbers. Using live imaging analysis, we also characterize a novel role for Sybu in the collection of germ plasm in vegetal cleavage furrows by surface contraction waves. Additionally, we show that a localized kinesin-like protein, Kif3b, is also required for germ plasm aggregation and that Sybu functionally interacts with Kif3b and Kif4a in germ plasm aggregation. Overall, these data suggest multiple coordinate roles for kinesins and adaptor proteins in controlling the localization and distribution of a cytoplasmic determinant in early development. Copyright © 2017 Elsevier Inc. All rights reserved.

Functional Analysis of the Drosophila Embryonic Germ Cell Transcriptome by RNA Interference

PubMed Central

Bujna, Ágnes; Vilmos, Péter; Spirohn, Kerstin; Boutros, Michael; Erdélyi, Miklós

2014-01-01

In Drosophila melanogaster, primordial germ cells are specified at the posterior pole of the very early embryo. This process is regulated by the posterior localized germ plasm that contains a large number of RNAs of maternal origin. Transcription in the primordial germ cells is actively down-regulated until germ cell fate is established. Bulk expression of the zygotic genes commences concomitantly with the degradation of the maternal transcripts. Thus, during embryogenesis, maternally provided and zygotically transcribed mRNAs determine germ cell development collectively. In an effort to identify novel genes involved in the regulation of germ cell behavior, we carried out a large-scale RNAi screen targeting both maternal and zygotic components of the embryonic germ line transcriptome. We identified 48 genes necessary for distinct stages in germ cell development. We found pebble and fascetto to be essential for germ cell migration and germ cell division, respectively. Our data uncover a previously unanticipated role of mei-P26 in maintenance of embryonic germ cell fate. We also performed systematic co-RNAi experiments, through which we found a low rate of functional redundancy among homologous gene pairs. As our data indicate a high degree of evolutionary conservation in genetic regulation of germ cell development, they are likely to provide valuable insights into the biology of the germ line in general. PMID:24896584

Germ cells in the teleost fish medaka have an inherent feminizing effect

PubMed Central

Nishimura, Toshiya; Yamada, Kazuki; Fujimori, Chika; Kikuchi, Mariko; Kawasaki, Toshihiro; Siegfried, Kellee R.; Sakai, Noriyoshi

2018-01-01

Germ cells give rise to eggs or sperm. However, recent analyses in medaka (Oryzias latipes) showed that germ cells are also important for feminization of gonads, although this novel role of germ cells has not been characterized in detail. Here, we show that the feminizing effect is inherent to germ cells and is not affected by gametogenic stages or the sexual fate of germ cells. Three medaka mutants were generated to demonstrate this effect: figlα mutants, in which follicle formation is disrupted; meioC mutants, in which germ cells are unable to commit to gametogenesis and meiosis; and dazl mutants, in which germ cells do not develop into gonocytes. All these different stages of germ cells in XX mutants have an ability to feminize the gonads, resulting in the formation of gonads with ovarian structures. In addition to normal ovarian development, we also suggest that the increased number of gonocytes is sufficient for male to female sex reversal in XY medaka. These results may genetically demonstrate that the mechanism underlying the feminizing effect of germ cells is activated before the sexual fate decision of germ cells and meiosis, probably by the time of gonocyte formation in medaka. Author summary Germ cells are the only cells that can transfer genetic materials to the next generation via the sperm or egg. However, recent analyses in teleosts revealed another essential role of germ cells: feminizing the gonads. In our study, medaka mutants in which gametogenesis was blocked at specific stages provides the novel view that the feminizing effect of germ cells occurs in parallel with other reproductive elements, such as meiosis, the sexual fate decision of germ cells, and gametogenesis. Germ cells in medaka may have a potential to feminize gonads at the moment they have developed. PMID:29596424

AiGERM: A logic programming front end for GERM

NASA Technical Reports Server (NTRS)

Hashim, Safaa H.

1990-01-01

AiGerm (Artificially Intelligent Graphical Entity Relation Modeler) is a relational data base query and programming language front end for MCC (Mission Control Center)/STP's (Space Test Program) Germ (Graphical Entity Relational Modeling) system. It is intended as an add-on component of the Germ system to be used for navigating very large networks of information. It can also function as an expert system shell for prototyping knowledge-based systems. AiGerm provides an interface between the programming language and Germ.

Charged Particle Dose Measurements by the Odyssey/MARIE Instrument in Mars Orbit and Model Calculations

NASA Technical Reports Server (NTRS)

Cleghorn, T. F.; Saganti, P. B.; Zeitlin, C.; Cucinotta, F. A.

2004-01-01

Knowledge of the space radiation environment is crucial both for human space exploration, and robotic space missions. It is likely that human explorers will return to the moon, and then go to Mars within the next thirty years. The radiation environment that they will encounter is a significant obstacle to future exploration, and must be dealt with successfully before longterm human missions outside of the magnetosphere can take place. Shielding technologies and materials must be developed to lower the dose and dose equivalent that human beings will receive on such missions. To begin this development, a fairly complete and accurate understanding of the space environment must be obtained. The major components of the space particle radiation environment that are most hazardous to humans are: galactic cosmic rays (GCR), the particles contained in solar particle events, (SPE), and secondary particles generated in material in the spacecraft itself. The intensity of the GCR varies by roughly a factor of two over the eleven-year solar cycle, inversely with the level of solar activity. These GCR particles are fully stripped nuclei, predominantly protons and helium, but also significant numbers of heavier ions, including carbon, oxygen, and iron. Since the ionization caused by nuclei passing through matter is proportional to the square of its charge (Z=10). The MARIE instrument has been described elsewhere.

Initiation-promotion model of tumor prevalence in mice from space radiation exposures

NASA Technical Reports Server (NTRS)

Cucinotta, F. A.; Wilson, J. W.

1995-01-01

Exposures in space consist of low-level background components from galactic cosmic rays (GCR), occasional intense-energetic solar-particle events, periodic passes through geomagnetic-trapped radiation, and exposure from possible onboard nuclear-propulsion engines. Risk models for astronaut exposure from such diverse components and modalities must be developed to assure adequate protection in future NASA missions. The low-level background exposures (GCR), including relativistic heavy ions (HZE), will be the ultimate limiting factor for astronaut career exposure. We consider herein a two-mutation, initiation-promotion, radiation-carcinogenesis model in mice in which the initiation stage is represented by a linear kinetics model of cellular repair/misrepair, including the track-structure model for heavy ion action cross-sections. The model is validated by comparison with the harderian gland tumor experiments of Alpen et al. for various ion beams. We apply the initiation-promotion model to exposures from galactic cosmic rays, using models of the cosmic-ray environment and heavy ion transport, and consider the effects of the age of the mice prior to and after the exposure and of the length of time in space on predictions of relative risk. Our results indicate that biophysical models of age-dependent radiation hazard will provide a better understanding of GCR risk than models that rely strictly on estimates of the initial slopes of these radiations.

Precipitation Behaviors of TiN Inclusion in GCr15 Bearing Steel Billet

NASA Astrophysics Data System (ADS)

Tian, Qianren; Wang, Guocheng; Zhao, Yang; Li, Jing; Wang, Qi

2018-06-01

There are many types of non-metallic TiN-based inclusions observed in GCr15 bearing steel, including single-particle TiN, multi-particle polymerized TiN, and complex inclusions like TiN-MnS, TiN-MgO-MgAl2O4 (TiN-MgO-MA), and TiN-MgAl2O4-MnS (TiN-MA-MnS). Thermodynamic calculations suggest that single-particle TiN precipitates dominate the mushy zone of GCr15 bearing steel. Kinetic calculations regarding TiN growth suggest that the final size of the single-particle TiN ranges between 1 and 6 μm in the initial concentration range of [pct Ti] = 0.0060 to 0.0079 and [pct N] = 0.0049 to 0.0070, at 1620 to 1640 K and a local cooling rate of 0.5 to 10 K/s. The multi-particle polymerized TiN are formed by single TiN particles in three stages: single-particle TiN inclusions approach each other drawn by the cavity bridge force (CBF), local active angles consolidate, and neck region sintering occurs. Based on the thermodynamic calculations of TiN, MnS, and MgO precipitation, the formation behaviors of complex inclusions of TiN-MnS, TiN-MgO-MA, and TiN-MA-MnS were investigated.

Identification of a putative germ plasm in the amphipod Parhyale hawaiensis

PubMed Central

2013-01-01

Background Specification of the germ line is an essential event during the embryonic development of sexually reproducing animals, as germ line cells are uniquely capable of giving rise to the next generation. Animal germ cells arise through either inheritance of a specialized, maternally supplied cytoplasm called 'germ plasm’ or though inductive signaling by somatic cells. Our understanding of germ cell determination is based largely on a small number of model organisms. To better understand the evolution of germ cell specification, we are investigating this process in the amphipod crustacean Parhyale hawaiensis. Experimental evidence from previous studies demonstrated that Parhyale germ cells are specified through inheritance of a maternally supplied cytoplasmic determinant; however, this determinant has not been identified. Results Here we show that the one-cell stage Parhyale embryo has a distinct cytoplasmic region that can be identified by morphology as well as the localization of germ line-associated RNAs. Removal of this cytoplasmic region results in a loss of embryonic germ cells, supporting the hypothesis that it is required for specification of the germ line. Surprisingly, we found that removal of this distinct cytoplasm also results in aberrant somatic cell behaviors, as embryos fail to gastrulate. Conclusions Parhyale hawaiensis embryos have a specialized cytoplasm that is required for specification of the germ line. Our data provide the first functional evidence of a putative germ plasm in a crustacean and provide the basis for comparative functional analysis of germ plasm formation within non-insect arthropods. PMID:24314239

Convergent evolution of germ granule nucleators: A hypothesis.

PubMed

Kulkarni, Arpita; Extavour, Cassandra G

2017-10-01

Germ cells have been considered "the ultimate stem cell" because they alone, during normal development of sexually reproducing organisms, are able to give rise to all organismal cell types. Morphological descriptions of a specialized cytoplasm termed 'germ plasm' and associated electron dense ribonucleoprotein (RNP) structures called 'germ granules' within germ cells date back as early as the 1800s. Both germ plasm and germ granules are implicated in germ line specification across metazoans. However, at a molecular level, little is currently understood about the molecular mechanisms that assemble these entities in germ cells. The discovery that in some animals, the gene products of a small number of lineage-specific genes initiate the assembly (also termed nucleation) of germ granules and/or germ plasm is the first step towards facilitating a better understanding of these complex biological processes. Here, we draw on research spanning over 100years that supports the hypothesis that these nucleator genes may have evolved convergently, allowing them to perform analogous roles across animal lineages. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Human DAZL, DAZ and BOULE genes modulate primordial germ cell and haploid gamete formation

PubMed Central

Kee, Kehkooi; Angeles, Vanessa T; Flores, Martha; Nguyen, Ha Nam; Pera, Renee A Reijo

2009-01-01

The leading cause of infertility in men and women is quantitative and qualitative defects in human germ cell (oocyte and sperm) development. Yet, it has not been possible to examine the unique developmental genetics of human germ cell formation and differentiation due to inaccessibility of germ cells during fetal development. Although several studies have shown that germ cells can be differentiated from mouse and human embryonic stem cells, human germ cells differentiated in these studies generally did not develop beyond the earliest stages1-8. Here we used a germ cell reporter to quantitate and isolate primordial germ cells derived from both male and female hESCs. Then, by silencing and overexpressing genes that encode germ cell-specific cytoplasmic RNA-binding proteins (not transcription factors), we modulated human germ cell formation and developmental progression. We observed that human DAZL (Deleted in AZoospermia-Like) functions in primordial germ cell formation, whereas closely-related genes, DAZ and BOULE, promote later stages of meiosis and development of haploid gametes. These results are significant to the generation of gametes for future basic science and potential clinical applications. PMID:19865085

PHASE II TRIAL OF THE CYCLIN-DEPEDENT KINASE INHIBITOR PD 0332991 IN PATIENTS WITH CANCER

ClinicalTrials.gov

2016-08-24

Adult Solid Tumor; Adenocarcinoma of the Colon; Adenocarcinoma of the Rectum; Adult Central Nervous System Germ Cell Tumor; Adult Teratoma; Benign Teratoma; Estrogen Receptor-negative Breast Cancer; Estrogen Receptor-positive Breast Cancer; Familial Testicular Germ Cell Tumor; HER2-negative Breast Cancer; HER2-positive Breast Cancer; Male Breast Cancer; Ovarian Immature Teratoma; Ovarian Mature Teratoma; Ovarian Monodermal and Highly Specialized Teratoma; Progesterone Receptor-negative Breast Cancer; Progesterone Receptor-positive Breast Cancer; Recurrent Breast Cancer; Recurrent Colon Cancer; Recurrent Extragonadal Germ Cell Tumor; Recurrent Extragonadal Non-seminomatous Germ Cell Tumor; Recurrent Extragonadal Seminoma; Recurrent Malignant Testicular Germ Cell Tumor; Recurrent Melanoma; Recurrent Ovarian Germ Cell Tumor; Recurrent Rectal Cancer; Stage III Extragonadal Non-seminomatous Germ Cell Tumor; Stage III Extragonadal Seminoma; Stage III Malignant Testicular Germ Cell Tumor; Stage III Ovarian Germ Cell Tumor; Stage IV Breast Cancer; Stage IV Colon Cancer; Stage IV Extragonadal Non-seminomatous Germ Cell Tumor; Stage IV Extragonadal Seminoma; Stage IV Melanoma; Stage IV Ovarian Germ Cell Tumor; Stage IV Rectal Cancer; Testicular Immature Teratoma; Testicular Mature Teratoma

Standard-Dose Combination Chemotherapy or High-Dose Combination Chemotherapy and Stem Cell Transplant in Treating Patients With Relapsed or Refractory Germ Cell Tumors

ClinicalTrials.gov

2018-06-08

Germ Cell Tumor; Teratoma; Choriocarcinoma; Germinoma; Mixed Germ Cell Tumor; Yolk Sac Tumor; Childhood Teratoma; Malignant Germ Cell Neoplasm; Extragonadal Seminoma; Non-seminomatous Germ Cell Tumor; Seminoma

Primordial Germ Cell Specification and Migration

PubMed Central

Marlow, Florence

2015-01-01

Primordial germ cells are the progenitor cells that give rise to the gametes. In some animals, the germline is induced by zygotic transcription factors, whereas in others, primordial germ cell specification occurs via inheritance of maternally provided gene products known as germ plasm. Once specified, the primordial germ cells of some animals must acquire motility and migrate to the gonad in order to survive. In all animals examined, perinuclear structures called germ granules form within germ cells. This review focuses on some of the recent studies, conducted by several groups using diverse systems, from invertebrates to vertebrates, which have provided mechanistic insight into the molecular regulation of germ cell specification and migration. PMID:26918157

The Heavy Nuclei eXplorer (HNX) Mission

NASA Technical Reports Server (NTRS)

Binns, W. R.; Adams, J. H.; Barbier, L. M.; Craig, N.; Cummings, A. C.; Cummings, J. R.; Doke, T.; Hasebe, N.; Hayashi, T.; Whitaker, Ann F. (Technical Monitor)

2001-01-01

The primary scientific objectives of HNX, which was recently selected by NASA for a Small Explorer (SMEX) Mission Concept Study, are to measure the age of the galactic cosmic rays (GCR) since nucleosynthesis, determine the injection mechanism for the GCR accelerator (Volatility or FIP), and study the mix of nucleosynthetic processes that contribute to the source of GCRs. The experimental goal of HNX is to measure the elemental abundances of all individual stable nuclei from neon through the actinides and possibly beyond. HNX is composed of two instruments: ECCO, which measures elemental abundances of nuclei with Z greater than or equal to 72, and ENTICE. which measures elemental abundances of nuclei with Z between 10 and 82. We describe the mission and the science that can be addressed by HNX.

Phenotypic and Molecular Analysis of Mes-3, a Maternal-Effect Gene Required for Proliferation and Viability of the Germ Line in C. Elegans

PubMed Central

Paulsen, J. E.; Capowski, E. E.; Strome, S.

1995-01-01

mes-3 is one of four maternal-effect sterile genes that encode maternal components required for normal postembryonic development of the germ line in Caenorhabditis elegans. mes-3 mutant mothers produce sterile progeny, which contain few germ cells and no gametes. This terminal phenotype reflects two problems: reduced proliferation of the germ line and germ cell death. Both the appearance of the dying germ cells and the results of genetic tests indicate that germ cells in mes-3 animals undergo a necrotic-like death, not programmed cell death. The few germ cells that appear healthy in mes-3 worms do not differentiate into gametes, even after elimination of the signaling pathway that normally maintains the undifferentiated population of germ cells. Thus, mes-3 encodes a maternally supplied product that is required both for proliferation of the germ line and for maintenance of viable germ cells that are competent to differentiate into gametes. Cloning and molecular characterization of mes-3 revealed that it is the upstream gene in an operon. The genes in the operon display parallel expression patterns; transcripts are present throughout development and are not restricted to germ-line tissue. Both mes-3 and the downstream gene in the operon encode novel proteins. PMID:8601481

Deep Space Test Bed for Radiation Studies

NASA Technical Reports Server (NTRS)

Adams, James H.; Christl, Mark; Watts, John; Kuznetsov, Eugene; Lin, Zi-Wei

2006-01-01

A key factor affecting the technical feasibility and cost of missions to Mars or the Moon is the need to protect the crew from ionizing radiation in space. Some analyses indicate that large amounts of spacecraft shielding may be necessary for crew safety. The shielding requirements are driven by the need to protect the crew from Galactic cosmic rays (GCR). Recent research activities aimed at enabling manned exploration have included shielding materials studies. A major goal of this research is to develop accurate radiation transport codes to calculate the shielding effectiveness of materials and to develop effective shielding strategies for spacecraft design. Validation of these models and calculations must be addressed in a relevant radiation environment to assure their technical readiness and accuracy. Test data obtained in the deep space radiation environment can provide definitive benchmarks and yield uncertainty estimates of the radiation transport codes. The two approaches presently used for code validation are ground based testing at particle accelerators and flight tests in high-inclination low-earth orbits provided by the shuttle, free-flyer platforms, or polar-orbiting satellites. These approaches have limitations in addressing all the radiation-shielding issues of deep space missions in both technical and practical areas. An approach based on long duration high altitude polar balloon flights provides exposure to the galactic cosmic ray composition and spectra encountered in deep space at a lower cost and with easier and more frequent access than afforded with spaceflight opportunities. This approach also results in shorter development times than spaceflight experiments, which is important for addressing changing program goals and requirements.

Molecular cloning of a Candida albicans gene (SSB1) coding for a protein related to the Hsp70 family.

PubMed

Maneu, V; Cervera, A M; Martinez, J P; Gozalbo, D

1997-06-15

We have cloned and sequenced a Candida albicans gene (SSB1) encoding a potential member of the heat-shock protein seventy (hsp70) family. The protein encoded by this gene contains 613 amino acids and shows a high degree (85%) of sequence identity to the ssb subfamily (ssb1 and ssb2) of the Saccharomyces cerevisiae hsp70 family. The transcribed mRNA (2.1 kb) is present in similar amounts both in yeast and germ tube cells of C. albicans.

Primary Culture System for Germ Cells from Caenorhabditis elegans Tumorous Germline Mutants

PubMed Central

Vagasi, Alexandra S.; Rahman, Mohammad M.; Chaudhari, Snehal N.; Kipreos, Edward T.

2017-01-01

The Caenorhabditis elegans germ line is an important model system for the study of germ stem cells. Wild-type C. elegans germ cells are syncytial and therefore cannot be isolated in in vitro cultures. In contrast, the germ cells from tumorous mutants can be fully cellularized and isolated intact from the mutant animals. Here we describe a detailed protocol for the isolation of germ cells from tumorous mutants that allows the germ cells to be maintained for extended periods in an in vitro primary culture. This protocol has been adapted from Chaudhari et al., 2016. PMID:28868332

Structure and Expression of Hybrid Dysgenesis-Induced Alleles of the Ovarian Tumor (Otu) Gene in Drosophila Melanogaster

PubMed Central

Sass, G. L.; Mohler, J. D.; Walsh, R. C.; Kalfayan, L. J.; Searles, L. L.

1993-01-01

Mutations at the ovarian tumor (otu) gene of Drosophila melanogaster cause female sterility and generate a range of ovarian phenotypes. Quiescent (QUI) mutants exhibit reduced germ cell proliferation; in oncogenic (ONC) mutants germ cells undergo uncontrolled proliferation generating excessive numbers of undifferentiated cells; the egg chambers of differentiated (DIF) mutants differentiate to variable degrees but fail to complete oogenesis. We have examined mutations caused by insertion and deletion of P elements at the otu gene. The P element insertion sites are upstream of the major otu transcription start sites. In deletion derivatives, the P element, regulatory regions and/or protein coding sequences have been removed. In both insertion and deletion mutants, the level of otu expression correlates directly with the severity of the phenotype: the absence of otu function produces the most severe QUI phenotype while the ONC mutants express lower levels of otu than those which are DIF. The results of this study demonstrate that the diverse mutant phenotypes of otu are the consequence of different levels of otu function. PMID:8436274

piRNA-directed cleavage of meiotic transcripts regulates spermatogenesis.

PubMed

Goh, Wee Siong Sho; Falciatori, Ilaria; Tam, Oliver H; Burgess, Ralph; Meikar, Oliver; Kotaja, Noora; Hammell, Molly; Hannon, Gregory J

2015-05-15

MIWI catalytic activity is required for spermatogenesis, indicating that piRNA-guided cleavage is critical for germ cell development. To identify meiotic piRNA targets, we augmented the mouse piRNA repertoire by introducing a human meiotic piRNA cluster. This triggered a spermatogenesis defect by inappropriately targeting the piRNA machinery to mouse mRNAs essential for germ cell development. Analysis of such de novo targets revealed a signature for pachytene piRNA target recognition. This enabled identification of both transposable elements and meiotically expressed protein-coding genes as targets of native piRNAs. Cleavage of genic targets began at the pachytene stage and resulted in progressive repression through meiosis, driven at least in part via the ping-pong cycle. Our data support the idea that meiotic piRNA populations must be strongly selected to enable successful spermatogenesis, both driving the response away from essential genes and directing the pathway toward mRNA targets that are regulated by small RNAs in meiotic cells. © 2015 Goh et al.; Published by Cold Spring Harbor Laboratory Press.

Urinary trace element concentrations in environmental settings: is there a value for systematic creatinine adjustment or do we introduce a bias?

PubMed

Hoet, Perrine; Deumer, Gladys; Bernard, Alfred; Lison, Dominique; Haufroid, Vincent

2016-01-01

Systematic creatinine adjustment of urinary concentrations of biomarkers has been a challenge over the past years because the assumption of a constant creatinine excretion rate appears erroneous and the issue of overadjustment has recently emerged. This study aimed at determining whether systematic creatinine adjustment is to be recommended for urinary concentrations of trace elements (TEs) in environmental settings. Paired 24-h collection and random spot urine samples (spotU) were obtained from 39 volunteers not occupationally exposed to TEs. Four models to express TEs concentration in spotU were tested to predict the 24-h excretion rate of these TEs (TEμg/24h) considered as the gold standard reference: absolute concentration (TEμg/l); ratio to creatinine (TEμg/gcr); TEμg/gcr adjusted to creatinine (TEμg/gcr-adj); and concentration adjusted to specific gravity (TEμg/l-SG). As, Ba, Cd, Co, Cr, Cu, Hg, Li, Mo, Ni, Pb, Sn, Sb, Se, Te, V and Zn were analyzed by inductively coupled argon plasma mass spectrometry. There was no single pattern of relationship between urinary TEs concentrations in spotU and TEμg/24h. TEμg/l predicted TEμg/24h with an explained variance ranging from 0 to 60%. Creatinine adjustment improved the explained variance by an additional 5 to ~60% for many TEs, but with a risk of overadjustment for the most of them. This issue could be addressed by adjusting TE concentrations on the basis of the regression coefficient of the relationship between TEμg/gcr and creatinine concentration. SG adjustment was as suitable as creatinine adjustment to predict TEμg/24h with no SG-overadjustment (except V). Regarding Cd, Cr, Cu, Ni and Te, none of the models were found to reflect TEμg/24h. In the context of environmental exposure, systematic creatinine adjustment is not recommended for urinary concentrations of TEs. SG adjustment appears to be a more reliable alternative. For some TEs, however, neither methods appear suitable.

Quantitative Differences in a Single Maternal Factor Determine Survival Probabilities among Drosophila Germ Cells.

PubMed

Slaidina, Maija; Lehmann, Ruth

2017-01-23

Germ cell death occurs in many species [1-3] and has been proposed as a mechanism by which the fittest, strongest, or least damaged germ cells are selected for transmission to the next generation. However, little is known about how the choice is made between germ cell survival and death. Here, we focus on the mechanisms that regulate germ cell survival during embryonic development in Drosophila. We find that the decision to die is a germ cell-intrinsic process linked to quantitative differences in germ plasm inheritance, such that higher germ plasm inheritance correlates with higher primordial germ cell (PGC) survival probability. We demonstrate that the maternal factor lipid phosphate phosphatase Wunen-2 (Wun2) regulates PGC survival in a dose-dependent manner. Since wun2 mRNA levels correlate with the levels of other maternal determinants at the single-cell level, we propose that Wun2 is used as a readout of the overall germ plasm quantity, such that only PGCs with the highest germ plasm quantity survive. Furthermore, we demonstrate that Wun2 and p53, another regulator of PGC survival, have opposite yet independent effects on PGC survival. Since p53 regulates cell death upon DNA damage and various cellular stresses, we hypothesize that together they ensure selection of the PGCs with highest germ plasm quantity and least cellular damage. Copyright © 2017 Elsevier Ltd. All rights reserved.

The Geochemical Earth Reference Model (GERM)

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

Staudigel, H.; Albarede, F.; Shaw, H.

The Geochemical Earth Reference Model (GERM) initiative is a grass- roots effort with the goal of establishing a community consensus on a chemical characterization of the Earth, its major reservoirs, and the fluxes between them. Long term goal of GERM is a chemical reservoir characterization analogous to the geophysical effort of the Preliminary Reference Earth Model (PREM). Chemical fluxes between reservoirs are included into GERM to illuminate the long-term chemical evolution of the Earth and to characterize the Earth as a dynamic chemical system. In turn, these fluxes control geological processes and influence hydrosphere-atmosphere-climate dynamics. While these long-term goals aremore » clearly the focus of GERM, the process of establishing GERM itself is just as important as its ultimate goal. The GERM initiative is developed in an open community discussion on the World Wide Web (GERM home page is at http://www-ep.es.llnl. gov/germ/germ-home.html) that is mediated by a series of editors with responsibilities for distinct reservoirs and fluxes. Beginning with the original workshop in Lyons (March 1996) GERM is continued to be developed on the Internet, punctuated by workshops and special sessions at professional meetings. It is planned to complete the first model by mid-1997, followed by a call for papers for a February 1998 GERM conference in La Jolla, California.« less

Models of germ cell development and their application for toxicity studies

PubMed Central

Ferreira, Daniel W.; Allard, Patrick

2015-01-01

Germ cells are unique in their ability to transfer genetic information and traits from generation to generation. As such, the proper development of germ cells and the integrity of their genome are paramount to the health of organisms and the survival of species. Germ cells are also exquisitely sensitive to environmental influences although the testing of germ cell toxicity, especially in females, has proven particularly challenging. In this review, we first describe the remarkable odyssey of germ cells in mammals, with an emphasis on the female germline, from their initial specification during embryogenesis to the generation of mature gametes in adults. We also describe the current methods used in germ cell toxicity testing and their limitations in examining the complex features of mammalian germ cell development. To bypass these challenges, we propose the use of alternative model systems such as Saccharomyces cerevisiae, Drosophila melanogaster, Caenorhabditis elegans and in vitro germ cell methods that have distinct advantages over traditional toxicity models. We discuss the benefits and limitations of each approach, their application to germ cell toxicity studies, and the need for computational approaches to maximize the usefulness of these models. Together, the inclusion of these alternative germ cell toxicity models will be invaluable for the examination of stages not easily accessible in mammals as well as the large scale, high-throughput investigation of germ cell toxicity. PMID:25821157

A functional Bucky ball-GFP transgene visualizes germ plasm in living zebrafish.

PubMed

Riemer, Stephan; Bontems, Franck; Krishnakumar, Pritesh; Gömann, Jasmin; Dosch, Roland

2015-01-01

In many animals, the germline is specified by maternal RNA-granules termed germ plasm. The correct localization of germ plasm during embryogenesis is therefore crucial for the specification of germ cells. In zebrafish, we previously identified Bucky ball (Buc) as a key regulator of germ plasm formation. Here, we used a Buc antibody to describe its continuous germ plasm localization. Moreover, we generated a transgenic Buc-GFP line for live imaging, which visualizes germ plasm from its assembly during oogenesis up to the larval stages. Live imaging of Buc-GFP generated stunning movies, as they highlighted the dynamic details of germ plasm movements. Moreover, we discovered that Buc was still detected in primordial germ cells 2 days after fertilization. Interestingly, the transgene rescued buc mutants demonstrating genetically that the Buc-GFP fusion protein is functional. These results show that Buc-GFP exerts all biochemical interactions essential for germline development and highlight the potential of this line to analyze the molecular regulation of germ plasm formation. Copyright © 2015 Elsevier B.V. All rights reserved.

Treatment Option Overview (Extragonadal Germ Cell Tumors)

MedlinePlus

... Professional Extragonadal Germ Cell Tumors Treatment Extragonadal Germ Cell Tumors Treatment (PDQ®)–Patient Version General Information About Extragonadal Germ Cell Tumors Go to Health Professional Version Key Points ...

Extraction and demulsification of oil from wheat germ, barley germ, and rice bran using an aqueous enzymatic method

USDA-ARS?s Scientific Manuscript database

An aqueous enzymatic method was developed to extract oil from wheat germ. The parameters that influence oil yield were investigated, including wheat germ pretreatment, comparison of various industrial enzymes, pH, ratio of wheat germ to water, reaction time and demulsification. Pretreatment at 180ºC...

The Biology of the Germ line in Echinoderms

PubMed Central

Wessel, Gary M.; Brayboy, Lynae; Fresques, Tara; Gustafson, Eric A.; Oulhen, Nathalie; Ramos, Isabela; Reich, Adrian; Swartz, S. Zachary; Yajima, Mamiko; Zazueta, Vanessa

2014-01-01

SUMMARY The formation of the germ line in an embryo marks a fresh round of reproductive potential. The developmental stage and location within the embryo where the primordial germ cells (PGCs) form, however, differs markedly among species. In many animals, the germ line is formed by an inherited mechanism, in which molecules made and selectively partitioned within the oocyte drive the early development of cells that acquire this material to a germ-line fate. In contrast, the germ line of other animals is fated by an inductive mechanism that involves signaling between cells that directs this specialized fate. In this review, we explore the mechanisms of germ-line determination in echinoderms, an early-branching sister group to the chordates. One member of the phylum, sea urchins, appears to use an inherited mechanism of germ-line formation, whereas their relatives, the sea stars, appear to use an inductive mechanism. We first integrate the experimental results currently available for germ line determination in the sea urchin, for which considerable new information is available, and then broaden the investigation to the lesser-known mechanisms in sea stars and other echinoderms. Even with this limited insight, it appears that sea stars, and perhaps the majority of the echinoderm taxon, rely on inductive mechanisms for germ-line fate determination. This enables a strongly contrasted picture for germ-line determination in this phylum, but one for which transitions between different modes of germ-line determination might now be experimentally addressed. PMID:23900765

Evolution of predetermined germ cells in vertebrate embryos: implications for macroevolution.

PubMed

Johnson, Andrew D; Drum, Matthew; Bachvarova, Rosemary F; Masi, Thomas; White, Mary E; Crother, Brian I

2003-01-01

The germ line is established in animal embryos with the formation of primordial germ cells (PGCs), which give rise to gametes. Therefore, the need to form PGCs can act as a developmental constraint by inhibiting the evolution of embryonic patterning mechanisms that compromise their development. Conversely, events that stabilize the PGCs may liberate these constraints. Two modes of germ cell determination exist in animal embryos: (a) either PGCs are predetermined by the inheritance of germ cell determinants (germ plasm) or (b) PGCs are formed by inducing signals secreted by embryonic tissues (i.e., regulative determination). Surprisingly, among the major extant amphibian lineages, one mechanism is found in urodeles and the other in anurans. In anuran amphibians PGCs are predetermined by germ plasm; in urodele amphibians PGCs are formed by inducing signals. To determine which mechanism is ancestral to the tetrapod lineage and to understand the pattern of inheritance in higher vertebrates, we used a phylogenetic approach to analyze basic morphological processes in both groups and correlated these with mechanisms of germ cell determination. Our results indicate that regulative germ cell determination is a property of embryos retaining ancestral embryological processes, whereas predetermined germ cells are found in embryos with derived morphological traits. These correlations suggest that regulative germ cell formation is an important developmental constraint in vertebrate embryos, acting before the highly conserved pharyngula stage. Moreover, our analysis suggests that germ plasm has evolved independently in several lineages of vertebrate embryos.

A summary of recent results from the GRAPES-3 experiment

NASA Astrophysics Data System (ADS)

Gupta, S. K.

2017-06-01

The GRAPES-3 experiment is a combination of a high density extensive air shower (EAS) array of nearly 400 plastic scintillator detectors, and a large 560 m2 area tracking muon telescope with an energy threshold Eμ >1 GeV. GRAPES-3 has been operating continuously in Ooty, India since 2000. By accurately correcting for the effects of atmospheric pressure and temperature, the muon telescope provides a high precision directional survey of the galactic cosmic ray (GCR) intensity. This telescope has been used to observe the acceleration of muons during thunderstorm events. The recent discovery of a transient weakening of the Earth's magnetic shield through the detection of a GCR burst was the highlight of the GRAPES-3 results. We have an ongoing major expansion activity to further enhance the capability of the GRAPES-3 muon telescope by doubling its area.

Investigations of Forbush decreases in the PAMELA experiment

NASA Astrophysics Data System (ADS)

Lagoida, I. A.; Voronov, S. A.; Mikhailov, V. V.

2017-01-01

A phenomenon in cosmic ray physics now called Forbush decrease (FD), or Forbush effect was discovered by S. Forbush in 1937 [1], it is a sudden decrease of galactic cosmic ray (GCR) intensity near the Earth. However, despite of the long term investigations the nature of this phenomenon is still not completely understood. Today this effect is studied mostly by the neutron monitors and muon hodoscopes, which are located on the Earth’s surface. But these monitors can detect only products of GCR interaction with the Earth atmosphere. Satellite detectors allow to obtain more accurate information about the characteristics of FD. Examples of FDs registered by the PAMELA telescope and observed with Oulu neutron monitor are presented. About 10 events with amplitude more than 3% have been registered from 2006 till 2016 with the PAMELA experiment.

Cosmic-ray record in solar system matter

NASA Technical Reports Server (NTRS)

Reedy, R. C.; Arnold, J. R.; Lal, D.

1983-01-01

The interaction of galactic cosmic rays (GCR) and solar cosmic rays (SCR) with bodies in the solar system is discussed, and what the record of that interaction reveals about the history of the solar system is considered. The influence of the energy, charge, and mass of the particles on the interaction is addressed, showing long-term average fluxes of solar protons, predicted production rates for heavy-nuclei tracks and various radionuclides as a function of depth in lunar rock, and integral fluxes of protons emitted by solar flares. The variation of the earth's magnetic field, the gardening of the lunar surface, and the source of meteorites and cosmic dust are studied using the cosmic ray record. The time variation of GCR, SCR, and VH and VVH nuclei is discussed for both the short and the long term.

Badhwar - O'Neill 2014 Galactic Cosmic Ray Flux Model Description

NASA Technical Reports Server (NTRS)

O'Neill, P. M.; Golge, S.; Slaba, T. C.

2014-01-01

The Badhwar-O'Neill (BON) Galactic Cosmic Ray (GCR) model is based on GCR measurements from particle detectors. The model has mainly been used by NASA to certify microelectronic systems and the analysis of radiation health risks to astronauts in space missions. The BON14 model numerically solves the Fokker-Planck differential equation to account for particle transport in the heliosphere due to diffusion, convection, and adiabatic deceleration under the assumption of a spherically symmetric heliosphere. The model also incorporates an empirical time delay function to account for the lag of the solar activity to reach the boundary of the heliosphere. This technical paper describes the most recent improvements in parameter fits to the BON model (BON14). Using a comprehensive measurement database, it is shown that BON14 is significantly improved over the previous version, BON11.

Galactic Cosmic Rays in the Outer Heliosphere

NASA Technical Reports Server (NTRS)

Florinski, V.; Washimi, H.; Pogorelov, N. V.; Adams, J. H.

2010-01-01

We report a next generation model of galactic cosmic ray (GCR) transport in the three dimensional heliosphere. Our model is based on an accurate three-dimensional representation of the heliospheric interface. This representation is obtained by taking into account the interaction between partially ionized, magnetized plasma flows of the solar wind and the local interstellar medium. Our model reveals that after entering the heliosphere GCRs are stored in the heliosheath for several years. The preferred GCR entry locations are near the nose of the heliopause and at high latitudes. Low-energy (hundreds of MeV) galactic ions observed in the heliosheath have spent, on average, a longer time in the solar wind than those observed in the inner heliosphere, which would explain their cooled-off spectra at these energies. We also discuss radial gradients in the heliosheath and the implications for future Voyager observations

Probabilistic Assessment of Radiation Risk for Astronauts in Space Missions

NASA Technical Reports Server (NTRS)

Kim, Myung-Hee; DeAngelis, Giovanni; Cucinotta, Francis A.

2009-01-01

Accurate predictions of the health risks to astronauts from space radiation exposure are necessary for enabling future lunar and Mars missions. Space radiation consists of solar particle events (SPEs), comprised largely of medium energy protons, (less than 100 MeV); and galactic cosmic rays (GCR), which include protons and heavy ions of higher energies. While the expected frequency of SPEs is strongly influenced by the solar activity cycle, SPE occurrences themselves are random in nature. A solar modulation model has been developed for the temporal characterization of the GCR environment, which is represented by the deceleration potential, phi. The risk of radiation exposure from SPEs during extra-vehicular activities (EVAs) or in lightly shielded vehicles is a major concern for radiation protection, including determining the shielding and operational requirements for astronauts and hardware. To support the probabilistic risk assessment for EVAs, which would be up to 15% of crew time on lunar missions, we estimated the probability of SPE occurrence as a function of time within a solar cycle using a nonhomogeneous Poisson model to fit the historical database of measurements of protons with energy > 30 MeV, (phi)30. The resultant organ doses and dose equivalents, as well as effective whole body doses for acute and cancer risk estimations are analyzed for a conceptual habitat module and a lunar rover during defined space mission periods. This probabilistic approach to radiation risk assessment from SPE and GCR is in support of mission design and operational planning to manage radiation risks for space exploration.

Space Radiation Cancer Risks and Uncertainities for Different Mission Time Periods

NASA Technical Reports Server (NTRS)

Kim,Myung-Hee Y.; Cucinotta, Francis A.

2012-01-01

Space radiation consists of solar particle events (SPEs), comprised largely of medium energy protons (less than several hundred MeV); and galactic cosmic ray (GCR), which includes high energy protons and high charge and energy (HZE) nuclei. For long duration missions, space radiation presents significant health risks including cancer mortality. Probabilistic risk assessment (PRA) is essential for radiation protection of crews on long term space missions outside of the protection of the Earth s magnetic field and for optimization of mission planning and costs. For the assessment of organ dosimetric quantities and cancer risks, the particle spectra at each critical body organs must be characterized. In implementing a PRA approach, a statistical model of SPE fluence was developed, because the individual SPE occurrences themselves are random in nature while the frequency distribution of SPEs depends strongly upon the phase within the solar activity cycle. Spectral variability of SPEs was also examined, because the detailed energy spectra of protons are important especially at high energy levels for assessing the cancer risk associated with energetic particles for large events. An overall cumulative probability of a GCR environment for a specified mission period was estimated for the temporal characterization of the GCR environment represented by the deceleration potential (theta). Finally, this probabilistic approach to space radiation cancer risk was coupled with a model of the radiobiological factors and uncertainties in projecting cancer risks. Probabilities of fatal cancer risk and 95% confidence intervals will be reported for various periods of space missions.

Nested Krylov methods and preserving the orthogonality

NASA Technical Reports Server (NTRS)

Desturler, Eric; Fokkema, Diederik R.

1993-01-01

Recently the GMRESR inner-outer iteraction scheme for the solution of linear systems of equations was proposed by Van der Vorst and Vuik. Similar methods have been proposed by Axelsson and Vassilevski and Saad (FGMRES). The outer iteration is GCR, which minimizes the residual over a given set of direction vectors. The inner iteration is GMRES, which at each step computes a new direction vector by approximately solving the residual equation. However, the optimality of the approximation over the space of outer search directions is ignored in the inner GMRES iteration. This leads to suboptimal corrections to the solution in the outer iteration, as components of the outer iteration directions may reenter in the inner iteration process. Therefore we propose to preserve the orthogonality relations of GCR in the inner GMRES iteration. This gives optimal corrections; however, it involves working with a singular, non-symmetric operator. We will discuss some important properties, and we will show by experiments that, in terms of matrix vector products, this modification (almost) always leads to better convergence. However, because we do more orthogonalizations, it does not always give an improved performance in CPU-time. Furthermore, we will discuss efficient implementations as well as the truncation possibilities of the outer GCR process. The experimental results indicate that for such methods it is advantageous to preserve the orthogonality in the inner iteration. Of course we can also use iteration schemes other than GMRES as the inner method; methods with short recurrences like GICGSTAB are of interest.

Exposure of the Bone Marrow Microenvironment to Simulated Solar and Galactic Cosmic Radiation Induces Biological Bystander Effects on Human Hematopoiesis.

PubMed

Almeida-Porada, Graça; Rodman, Christopher; Kuhlman, Bradford; Brudvik, Egil; Moon, John; George, Sunil; Guida, Peter; Sajuthi, Satria P; Langefeld, Carl D; Walker, Stephen J; Wilson, Paul F; Porada, Christopher D

2018-04-26

The stem cell compartment of the hematopoietic system constitutes one of the most radiosensitive tissues of the body and leukemias represent one of the most frequent radiogenic cancers with short latency periods. As such, leukemias may pose a particular threat to astronauts during prolonged space missions. Control of hematopoiesis is tightly governed by a specialized bone marrow (BM) microenvironment/niche. As such, any environmental insult that damages cells of this niche would be expected to produce pronounced effects on the types and functionality of hematopoietic/immune cells generated. We recently reported that direct exposure of human hematopoietic stem cells (HSC) to simulated solar energetic particle (SEP) and galactic cosmic ray (GCR) radiation dramatically altered the differentiative potential of these cells, and that simulated GCR exposures can directly induce DNA damage and mutations within human HSC, which led to leukemic transformation when these cells repopulated murine recipients. In this study, we performed the first in-depth examination to define changes that occur in mesenchymal stem cells present in the human BM niche following exposure to accelerated protons and iron ions and assess the impact these changes have upon human hematopoiesis. Our data provide compelling evidence that simulated SEP/GCR exposures can also contribute to defective hematopoiesis/immunity through so-called "biological bystander effects" by damaging the stromal cells that comprise the human marrow microenvironment, thereby altering their ability to support normal hematopoiesis.

Evaluation of the new radiation belt AE9/AP9/SPM model for a cislunar mission

NASA Astrophysics Data System (ADS)

Badavi, Francis F.; Walker, Steven A.; Santos Koos, Lindsey M.

2014-09-01

Space mission planners continue to experience challenges associated with human space flight. Concerned with the omnipresence of harmful ionizing radiation in space, at the mission design stage, mission planners must evaluate the amount of exposure the crew of a spacecraft is subjected to during the transit trajectory from low Earth orbit (LEO) to geosynchronous orbit (GEO) and beyond (free space). The Earth's geomagnetic field is located within the domain of LEO-GEO and, depending on latitude, extends out some 40,000-60,000 km. This field contains the Van Allen trapped electrons, protons, and low-energy plasmas, such as the nuclei of hydrogen, helium, oxygen, and to a lesser degree other atoms. In addition, there exist the geomagnetically attenuated energetic galactic cosmic rays (GCR). These particles are potentially harmful to improperly shielded crew members and onboard subsystems. Mitigation strategies to limit the exposure due to free space GCR and sporadic solar energetic particles (SEP) such as flare and coronal mass ejection (CME) must also be exercised beyond the trapped field. Presented in this work is the exposure analysis for a multi-vehicle mission planned for the epoch of February 2020 from LEO to the Earth-moon Lagrange-point two (L2), located approximately 63,000 km beyond the orbit of the Earth-moon binary system. Space operation at L2 provides a gravitationally stable orbit for a vehicle and partially eliminates the need for periodic thrust-vectoring to maintain orbital stability. In the cislunar (Earth-moon) space of L2, the mission trajectory and timeline in this work call for a cargo vehicle to rendezvous with a crew vehicle. This is followed by 15 days of space activities at L2 while the cargo and crew vehicles are docked after which the crew returns to Earth. The mission epoch of 2020 is specifically chosen as it is anticipated that the next solar minimum (i.e. end of cycle 24) in the Sun's approximate 11 years cycle will take place around this time. From a mission planning point of view, this date is ideal as the predictable GCR exposure will be at a maximum, while the sporadic SEP will be at a minimum. In addition, it is anticipated that by 2020 a vehicle capable of launching a crew of four will be operationally ready. During the LEO-GEO transit, the crew and cargo vehicles will encounter exposure from trapped particles and attenuated GCR, followed by free space exposure due to GCR and SEP during solar active times. Within the trapped field, a challenge arises from properly calculating the amount of exposure acquired. Within this field, in the absence of SEP (i.e. solar quiet times), the vehicles will have to transit through an inner proton belt, an inner and outer electron belts, and an attenuated GCR field. There exist a number of models to define the intensities of the trapped particles during the quiet and active SEP. Among the more established trapped models are the historic and popular electron/proton AE8/AP8 model dating back to the 1980s, the historic and less popular electron/proton CRRES model dating back to 1990s, and the recently released electron/proton/space plasma AE9/AP9/SPM model. The AE9/AP9/SPM model is a major improvement over the older AE8/AP8 and CRRES models. This model is derived from numerous measurements acquired over four solar cycles dating back to the 1970s, roughly representing 40 years of data collection. In contrast, the older AE8/AP8 and CRRES models were limited to only a few months of measurements taken during the prior solar minima and maxima. In this work, within the trapped field, along the design trajectory of the crew vehicle, the AE9/AP9/SPM model is evaluated against the older AE8/AP8 model during solar quiet times. The analysis is then extended to the GCR dominated en-route, cislunar L2 space and return trajectories in order to provide cumulative exposure estimates to the crew vehicle for the duration of the entire mission.

Ovarian Germ Cell Tumors Symptoms, Tests, Prognosis, and Stages (PDQ®)—Patient Version

Cancer.gov

Ovarian germ cell tumors form in germ (egg) cells in the ovary. Ovarian germ cell tumors usually occur in teenage girls or young women and most often affect just one ovary. They are usually cured if found and treated early. Learn about signs and symptoms, tests to diagnose, and stages of ovarian germ cell tumors.

Quantification of healthy and atretic germ cells and follicles in the developing and post-natal ovary of the South American plains vizcacha, Lagostomus maximus: evidence of continuous rise of the germinal reserve.

PubMed

Inserra, P I F; Leopardo, N P; Willis, M A; Freysselinard, A L; Vitullo, A D

2014-02-01

The female germ line in mammals is subjected to massive cell death that eliminates 60-85% of the germinal reserve by birth and continues from birth to adulthood until the exhaustion of the germinal pool. Germ cell demise occurs mainly through apoptosis by means of a biased expression in favour of pro-apoptotic members of the BCL2 gene family. By contrast, the South American plains vizcacha, Lagostomus maximus, exhibits sustained expression of the anti-apoptotic BCL2 gene throughout gestation and a low incidence of germ cell apoptosis. This led to the proposal that, in the absence of death mechanisms other than apoptosis, the female germ line should increase continuously from foetal life until after birth. In this study, we quantified all healthy germ cells and follicles in the ovaries of L. maximus from early foetal life to day 60 after birth using unbiased stereological methods and detected apoptosis by labelling with TUNEL assay. The healthy germ cell population increased continuously from early-developing ovary reaching a 50 times higher population number by the end of gestation. TUNEL-positive germ cells were <0.5% of the germ cell number, except at mid-gestation (3.62%). Mitotic proliferation, entrance into prophase I stage and primordial follicle formation occurred as overlapping processes from early pregnancy to birth. Germ cell number remained constant in early post-natal life, but a remnant population of non-follicular VASA- and PCNA-positive germ cells still persisted at post-natal day 60. L. maximus is the first mammal so far described in which female germ line develops in the absence of constitutive massive germ cell elimination.

Coherent Somatic Mutation in Autoimmune Disease

PubMed Central

Ross, Kenneth Andrew

2014-01-01

Background Many aspects of autoimmune disease are not well understood, including the specificities of autoimmune targets, and patterns of co-morbidity and cross-heritability across diseases. Prior work has provided evidence that somatic mutation caused by gene conversion and deletion at segmentally duplicated loci is relevant to several diseases. Simple tandem repeat (STR) sequence is highly mutable, both somatically and in the germ-line, and somatic STR mutations are observed under inflammation. Results Protein-coding genes spanning STRs having markers of mutability, including germ-line variability, high total length, repeat count and/or repeat similarity, are evaluated in the context of autoimmunity. For the initiation of autoimmune disease, antigens whose autoantibodies are the first observed in a disease, termed primary autoantigens, are informative. Three primary autoantigens, thyroid peroxidase (TPO), phogrin (PTPRN2) and filaggrin (FLG), include STRs that are among the eleven longest STRs spanned by protein-coding genes. This association of primary autoantigens with long STR sequence is highly significant (). Long STRs occur within twenty genes that are associated with sixteen common autoimmune diseases and atherosclerosis. The repeat within the TTC34 gene is an outlier in terms of length and a link with systemic lupus erythematosus is proposed. Conclusions The results support the hypothesis that many autoimmune diseases are triggered by immune responses to proteins whose DNA sequence mutates somatically in a coherent, consistent fashion. Other autoimmune diseases may be caused by coherent somatic mutations in immune cells. The coherent somatic mutation hypothesis has the potential to be a comprehensive explanation for the initiation of many autoimmune diseases. PMID:24988487

Mitotic Arrest in Teratoma Susceptible Fetal Male Germ Cells

PubMed Central

Western, Patrick S.; Ralli, Rachael A.; Wakeling, Stephanie I.; Lo, Camden; van den Bergen, Jocelyn A.; Miles, Denise C.; Sinclair, Andrew H.

2011-01-01

Formation of germ cell derived teratomas occurs in mice of the 129/SvJ strain, but not in C57Bl/6 inbred or CD1 outbred mice. Despite this, there have been few comparative studies aimed at determining the similarities and differences between teratoma susceptible and non-susceptible mouse strains. This study examines the entry of fetal germ cells into the male pathway and mitotic arrest in 129T2/SvJ mice. We find that although the entry of fetal germ cells into mitotic arrest is similar between 129T2/SvJ, C57Bl/6 and CD1 mice, there were significant differences in the size and germ cell content of the testis cords in these strains. In 129T2/SvJ mice germ cell mitotic arrest involves upregulation of p27KIP1, p15INK4B, activation of RB, the expression of male germ cell differentiation markers NANOS2, DNMT3L and MILI and repression of the pluripotency network. The germ-line markers DPPA2 and DPPA4 show reciprocal repression and upregulation, respectively, while FGFR3 is substantially enriched in the nucleus of differentiating male germ cells. Further understanding of fetal male germ cell differentiation promises to provide insight into disorders of the testis and germ cell lineage, such as testis tumour formation and infertility. PMID:21674058

Developmentally regulated expression of APG-1, a member of heat shock protein 110 family in murine male germ cells.

PubMed

Kaneko, Y; Kimura, T; Nishiyama, H; Noda, Y; Fujita, J

1997-04-07

Apg-1 encodes a heat shock protein belonging to the heat shock protein 110 family, and is inducible by a 32 degrees C to 39 degrees C heat shock. Northern blot analysis of the testis from immature and adult mice, and of the purified germ cells revealed the quantitative change of the apg-1 transcripts during germ cell development. By in situ hybridization histochemistry the expressions of the apg-1 transcripts were detected in germ cells at specific stages of development including spermatocytes and spermatids. Although heat-induction of the apg-1 transcripts was observed in W/Wv mutant testis lacking germ cells, it was not detected in wild-type testis nor in the purified germ cells. Thus, the apg-1 expression is not heat-regulated but developmentally regulated in germ cells, suggesting that APG-1 plays a role in normal development of germ cells.

An in vivo proteomic analysis of the Me31B interactome in Drosophila germ granules.

PubMed

DeHaan, Hunter; McCambridge, Aidan; Armstrong, Brittany; Cruse, Carlie; Solanki, Dhruv; Trinidad, Jonathan C; Arkov, Alexey L; Gao, Ming

2017-11-01

Drosophila Me31B is a conserved protein of germ granules, ribonucleoprotein complexes essential for germ cell development. Me31B post-transcriptionally regulates mRNAs by interacting with other germ granule proteins. However, a Me31B interactome is lacking. Here, we use an in vivo proteomics approach to show that the Me31B interactome contains polypeptides from four functional groups: RNA regulatory proteins, glycolytic enzymes, cytoskeleton/motor proteins, and germ plasm components. We further show that Me31B likely colocalizes with the germ plasm components Tudor (Tud), Vasa, and Aubergine in the nuage and germ plasm and provide evidence that Me31B may directly bind to Tud in a symmetrically dimethylated arginine-dependent manner. Our study supports the role of Me31B in RNA regulation and suggests its novel roles in germ granule assembly and function. © 2017 Federation of European Biochemical Societies.

Intratubular germ cell neoplasia of the human testis: heterogeneous protein expression and relation to invasive potential

PubMed Central

Mitchell, Rod T; Camacho-Moll, Maria; Macdonald, Joni; Anderson, Richard A; Kelnar, Christopher JH; O’Donnell, Marie; Sharpe, Richard M; Smith, Lee B; Grigor, Ken M; Wallace, W Hamish B; Stoop, Hans; Wolffenbuttel, Katja P; Donat, Roland

2014-01-01

Testicular germ cell cancer develops from pre-malignant intratubular germ cell neoplasia, unclassified cells that are believed to arise from failure of normal maturation of fetal germ cells from gonocytes (OCT4+/ MAGEA4−) into pre-spermatogonia (OCT4−/MAGEA4+). Intratubular germ cell neoplasia cell subpopulations based on stage of germ cell differentiation have been described, however the importance of these subpopulations in terms of invasive potential has not been reported. We hypothesised that cells expressing an immature (OCT4+/MAGEA4−) germ cell profile would exhibit an increased proliferation rate compared to those with a mature profile (OCT4+/ MAGEA4+). Therefore, we performed triple immunofluorescence and stereology to quantify the different intratubular germ cell neoplasia cell subpopulations, based on expression of germ cell (OCT4, PLAP, AP2γ, MAGEA4, VASA) and proliferation (Ki67) markers, in testis sections from patients with pre-invasive disease, seminoma and non-seminoma. We compared these subpopulations with normal human fetal testis and with seminoma cells. Heterogeneity of protein expression was demonstrated in intratubular germ cell neoplasia cells with respect to gonocyte and spermatogonial markers. It included an embryonic/fetal germ cell subpopulation lacking expression of the definitive intratubular germ cell neoplasia marker OCT4, that did not correspond to a physiological (fetal) germ cell subpopulation. OCT4+/MAGEA4- cells showed a significantly increased rate of proliferation compared with the OCT4+/MAGEA4+ population (12.8 v 3.4%, p<0.0001) irrespective of histological tumour type, reflected in the predominance of OCT4+/MAGEA4− cells in the invasive tumour component. Surprisingly, OCT4+/MAGEA4− cells in patients with pre-invasive disease showed significantly higher proliferation compared to those with seminoma or non-seminoma (18.1 v 10.2 v 7.2%, p<0.05 respectively). In conclusion, this study has demonstrated that OCT4+/MAGEA4− cells are the most frequent and most proliferative cell population in tubules containing intratubular germ cell neoplasia, which appears to be an important factor in determining invasive potential of intratubular germ cell neoplasia to seminomas. PMID:24457464

nanos function is essential for development and regeneration of planarian germ cells.

PubMed

Wang, Yuying; Zayas, Ricardo M; Guo, Tingxia; Newmark, Phillip A

2007-04-03

Germ cells are required for the successful propagation of sexually reproducing species. Understanding the mechanisms by which these cells are specified and how their totipotency is established and maintained has important biomedical and evolutionary implications. Freshwater planarians serve as fascinating models for studying these questions. They can regenerate germ cells from fragments of adult tissues that lack reproductive structures, suggesting that inductive signaling is involved in planarian germ cell specification. To study the development and regeneration of planarian germ cells, we have functionally characterized an ortholog of nanos, a gene required for germ cell development in diverse organisms, from Schmidtea mediterranea. In the hermaphroditic strain of this species, Smed-nanos mRNA is detected in developing, regenerating, and mature ovaries and testes. However, it is not detected in the vast majority of newly hatched planarians or in small tissue fragments that will ultimately regenerate germ cells, consistent with an epigenetic origin of germ cells. We show that Smed-nanos RNA interference (RNAi) results in failure to develop, regenerate, or maintain gonads in sexual planarians. Unexpectedly, Smed-nanos mRNA is also detected in presumptive testes primordia of asexual individuals that reproduce strictly by fission. These presumptive germ cells are lost after Smed-nanos RNAi, suggesting that asexual planarians specify germ cells, but their differentiation is blocked downstream of Smed-nanos function. Our results reveal a conserved function of nanos in germ cell development in planarians and suggest that these animals will serve as useful models for dissecting the molecular basis of epigenetic germ cell specification.

Defatted wheat germ application: Influence on cookies' properties with regard to its particle size and dough moisture content.

PubMed

Petrović, Jovana; Rakić, Dušan; Fišteš, Aleksandar; Pajin, Biljana; Lončarević, Ivana; Tomović, Vladimir; Zarić, Danica

2017-10-01

The introduction of agro-food industry by-products rich in bioactive compounds represents major challenge in food industry sector. The influence of wheat germ particle size (<150 µm, 150-1000 µm, and 800-2000 µm), wheat germ content (5, 10, and 15%), and dough moisture content (20, 22, and 24%) on chemical, textural, and sensory characteristics of cookies was investigated using the Box-Behnken experimental design. The substitution of wheat flour with wheat germ increased the protein, fat, mineral, and fiber content of the cookies. The particle size of wheat germ affected the textural properties of cookies. As the particle size of wheat germ increased, the hardness of cookies decreased. The color of the cookie was most influenced by the interaction of dough moisture content and wheat germ particle size. Wheat germ level up to 15% had no significant effect on the sensory characteristics of cookies. A suitable combination of defatted wheat germ level, its particle size, and dough moisture content can improve the nutritional value of cookies, without causing a negative effect on the cookies' sensory characteristics.

Identification of Grandchildless Loci Whose Products Are Required for Normal Germ-Line Development in the Nematode Caenorhabditis Elegans

PubMed Central

Capowski, E. E.; Martin, P.; Garvin, C.; Strome, S.

1991-01-01

To identify genes that encode maternal components required for development of the germ line in the nematode Caenorhabditis elegans, we have screened for mutations that confer a maternal-effect sterile or ``grandchildless'' phenotype: homozygous mutant hermaphrodites produced by heterozygous mothers are themselves fertile, but produce sterile progeny. Our screens have identified six loci, defined by 21 mutations. This paper presents genetic and phenotypic characterization of four of the loci. The majority of mutations, those in mes-2, mes-3 and mes-4, affect postembryonic germ-line development; the progeny of mutant mothers undergo apparently normal embryogenesis but develop into agametic adults with 10-1000-fold reductions in number of germ cells. In contrast, mutations in mes-1 cause defects in cytoplasmic partitioning during embryogenesis, and the resulting larvae lack germ-line progenitor cells. Mutations in all of the mes loci primarily affect the germ line, and none disrupt the structural integrity of germ granules. This is in contrast to grandchildless mutations in Drosophila melanogaster, all of which disrupt germ granules and affect abdominal as well as germ-line development. PMID:1783292

An RNA tool kit to study the status of mouse ES cells: sex determination and stemness.

PubMed

Jay, F; Ciaudo, C

2013-09-01

Mouse embryonic stem cells (mESCs) are pluripotent stem cells derived from the inner cell mass of the blastocyst. They can be maintained under controlled culture conditions in a pluripotent state, or be induced to differentiate into all derivatives of the three primary germ layers: ectoderm, endoderm and mesoderm. Several studies have characterised the coding and non-coding (nc) RNA repertoires of mESCs, uncovering highly dynamic variations during the process of differentiation, but also qualitative differences pertaining to sex. For example, up-regulation of the long non-coding RNA Xist on the X chromosome induces gene silencing and X inactivation exclusively during female mESC differentiation. In contrast, specific small RNAs have been shown to be up-regulated during male mESC differentiation. Here, we illustrate how a small set of key coding and ncRNAs can be exploited as dynamic and sensitive markers of the stemness and/or the differentiation status of male or female mESC lines. We describe adapted techniques for the extended characterization and analysis of mESCs from as little material as that cultured in a single 75cm(2) flask. Copyright © 2013 Elsevier Inc. All rights reserved.

Insights into female germ cell biology: from in vivo development to in vitro derivations.

PubMed

Jung, Dajung; Kee, Kehkooi

2015-01-01

Understanding the mechanisms of human germ cell biology is important for developing infertility treatments. However, little is known about the mechanisms that regulate human gametogenesis due to the difficulties in collecting samples, especially germ cells during fetal development. In contrast to the mitotic arrest of spermatogonia stem cells in the fetal testis, female germ cells proceed into meiosis and began folliculogenesis in fetal ovaries. Regulations of these developmental events, including the initiation of meiosis and the endowment of primordial follicles, remain an enigma. Studying the molecular mechanisms of female germ cell biology in the human ovary has been mostly limited to spatiotemporal characterizations of genes or proteins. Recent efforts in utilizing in vitro differentiation system of stem cells to derive germ cells have allowed researchers to begin studying molecular mechanisms during human germ cell development. Meanwhile, the possibility of isolating female germline stem cells in adult ovaries also excites researchers and generates many debates. This review will mainly focus on presenting and discussing recent in vivo and in vitro studies on female germ cell biology in human. The topics will highlight the progress made in understanding the three main stages of germ cell developments: namely, primordial germ cell formation, meiotic initiation, and folliculogenesis.

C-X-C motif chemokine ligand 10 produced by mouse Sertoli cells in response to mumps virus infection induces male germ cell apoptosis

PubMed Central

Jiang, Qian; Wang, Fei; Shi, Lili; Zhao, Xiang; Gong, Maolei; Liu, Weihua; Song, Chengyi; Li, Qihan; Chen, Yongmei; Wu, Han; Han, Daishu

2017-01-01

Mumps virus (MuV) infection usually results in germ cell degeneration in the testis, which is an etiological factor for male infertility. However, the mechanisms by which MuV infection damages male germ cells remain unclear. The present study showed that C-X-C motif chemokine ligand 10 (CXCL10) is produced by mouse Sertoli cells in response to MuV infection, which induces germ cell apoptosis through the activation of caspase-3. CXC chemokine receptor 3 (CXCR3), a functional receptor of CXCL10, is constitutively expressed in male germ cells. Neutralizing antibodies against CXCR3 and an inhibitor of caspase-3 activation significantly inhibited CXCL10-induced male germ cell apoptosis. Furthermore, the tumor necrosis factor-α (TNF-α) upregulated CXCL10 production in Sertoli cells after MuV infection. The knockout of either CXCL10 or TNF-α reduced germ cell apoptosis in the co-cultures of germ cells and Sertoli cells in response to MuV infection. Local injection of MuV into the testes of mice confirmed the involvement of CXCL10 in germ cell apoptosis in vivo. These results provide novel insights into MuV-induced germ cell apoptosis in the testis. PMID:29072682

Intergenerational impact of paternal lifetime exposures to both folic acid deficiency and supplementation on reproductive outcomes and imprinted gene methylation.

PubMed

Ly, Lundi; Chan, Donovan; Aarabi, Mahmoud; Landry, Mylène; Behan, Nathalie A; MacFarlane, Amanda J; Trasler, Jacquetta

2017-07-01

Do paternal exposures to folic acid deficient (FD), and/or folic acid supplemented (FS) diets, throughout germ cell development adversely affect male germ cells and consequently offspring health outcomes? Male mice exposed over their lifetimes to both FD and FS diets showed decreased sperm counts and altered imprinted gene methylation with evidence of transmission of adverse effects to the offspring, including increased postnatal-preweaning mortality and variability in imprinted gene methylation. There is increasing evidence that disruptions in male germ cell epigenetic reprogramming are associated with offspring abnormalities and intergenerational disease. The fetal period is the critical time of DNA methylation pattern acquisition for developing male germ cells and an adequate supply of methyl donors is required. In addition, DNA methylation patterns continue to be remodeled during postnatal spermatogenesis. Previous studies have shown that lifetime (prenatal and postnatal) folic acid deficiency can alter the sperm epigenome and increase the incidence of fetal morphological abnormalities. Female BALB/c mice (F0) were placed on one of four amino-acid defined diets for 4 weeks before pregnancy and throughout pregnancy and lactation: folic acid control (Ctrl; 2 mg/kg), 7-fold folic acid deficient (7FD; 0.3 mg/kg), 10-fold high FS (10FS, 20 mg/kg) or 20-fold high FS (20FS, 40 mg/kg) diets. F1 males were weaned to their respective prenatal diets to allow for diet exposure during all windows of germline epigenetic reprogramming: the erasure, re-establishment and maintenance phases. F0 females were mated with chow-fed males to produce F1 litters whose germ cells were exposed to the diets throughout embryonic development. F1 males were subsequently mated with chow-fed female mice. Two F2 litters, unexposed to the experimental diets, were generated from each F1 male; one litter was collected at embryonic day (E)18.5 and one delivered and followed postnatally. DNA methylation at a global level and at the differentially methylated regions of imprinted genes (H19, Imprinted Maternally Expressed Transcript (Non-Protein Coding)-H19, Small Nuclear Ribonucleoprotein Polypeptide N-Snrpn, KCNQ1 Opposite Strand/Antisense Transcript 1 (Non-Protein Coding)-Kcnq1ot1, Paternally Expressed Gene 1-Peg1 and Paternally Expressed Gene 3-Peg3) was assessed by luminometric methylation analysis and bisulfite pyrosequencing, respectively, in F1 sperm, F2 E18.5 placenta and F2 E18.5 brain cortex. F1 males exhibited lower sperm counts following lifetime exposure to both folic acid deficiency and the highest dose of folic acid supplementation (20FS), (both P < 0.05). Post-implantation losses were increased amongst F2 E18.5 day litters from 20FS exposed F1 males (P < 0.05). F2 litters derived from both 7FD and 20FS exposed F1 males had significantly higher postnatal-preweaning pup death (both P < 0.05). Sperm from 10FS exposed males had increased variance in methylation across imprinted gene H19, P < 0.05; increased variance at a few sites within H19 was also found for the 7FD and 20FS groups (P < 0.05). While the 20FS diet resulted in inter-individual alterations in methylation across the imprinted genes Snrpn and Peg3 in F2 E18.5 placenta, ≥50% of individual sites tested in Peg1 and/or Peg3 were affected in the 7FD and 10FS groups. Inter-individual alterations in Peg1 methylation were found in F2 E18.5 day 10FS group brain cortex (P < 0.05). Not applicable. The cause of the increase in postnatal-preweaning mortality was not investigated post-mortem. Further studies are required to understand the mechanisms underlying the adverse effects of folic acid deficiency and supplementation on developing male germ cells. Genome-wide DNA and histone methylome studies as well as gene expression studies are required to better understand the links between folic acid exposures, an altered germ cell epigenome and offspring outcomes. The findings of this study provide further support for paternally transmitted environmental effects. The results indicate that both folic acid deficiency and high dose supplementation can be detrimental to germ cell development and reproductive fitness, in part by altering DNA methylation in sperm. This study was supported by a grant to J.M.T. from the Canadian Institutes of Health Research (CIHR #89944). The authors declare they have no conflicts of interest. © The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Changes in Brain Function in Patients With Stage I, Stage II, Stage III, or Stage IV Ovarian, Primary Peritoneal, or Fallopian Tube Cancer Who Are Receiving Chemotherapy

ClinicalTrials.gov

2018-04-11

Cognitive Side Effects of Cancer Therapy; Malignant Ovarian Epithelial Tumor; Ovarian Brenner Tumor; Ovarian Carcinosarcoma; Ovarian Choriocarcinoma; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Dysgerminoma; Ovarian Embryonal Carcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mixed Germ Cell Tumor; Ovarian Mucinous Cystadenocarcinoma; Ovarian Polyembryoma; Ovarian Sarcoma; Ovarian Seromucinous Carcinoma; Ovarian Serous Cystadenocarcinoma; Ovarian Teratoma; Ovarian Yolk Sac Tumor; Stage I Ovarian Cancer; Stage IA Fallopian Tube Cancer; Stage IA Ovarian Cancer; Stage IA Ovarian Germ Cell Tumor; Stage IB Fallopian Tube Cancer; Stage IB Ovarian Cancer; Stage IB Ovarian Germ Cell Tumor; Stage IC Fallopian Tube Cancer; Stage IC Ovarian Cancer; Stage IC Ovarian Germ Cell Tumor; Stage II Ovarian Cancer; Stage IIA Fallopian Tube Cancer; Stage IIA Ovarian Cancer; Stage IIA Ovarian Germ Cell Tumor; Stage IIB Fallopian Tube Cancer; Stage IIB Ovarian Cancer; Stage IIB Ovarian Germ Cell Tumor; Stage IIC Fallopian Tube Cancer; Stage IIC Ovarian Cancer; Stage IIC Ovarian Germ Cell Tumor; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Ovarian Germ Cell Tumor; Stage IIIA Primary Peritoneal Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Ovarian Germ Cell Tumor; Stage IIIB Primary Peritoneal Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Ovarian Germ Cell Tumor; Stage IIIC Primary Peritoneal Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Ovarian Germ Cell Tumor; Stage IV Primary Peritoneal Cancer; Undifferentiated Ovarian Carcinoma

Methods to study maternal regulation of germ cell specification in zebrafish

PubMed Central

Kaufman, O.H.; Marlow, F.L.

2016-01-01

The process by which the germ line is specified in the zebrafish embryo is under the control of maternal gene products that were produced during oogenesis. Zebrafish are highly amenable to microscopic observation of the processes governing maternal germ cell specification because early embryos are transparent, and the germ line is specified rapidly (within 4–5 h post fertilization). Advantages of zebrafish over other models used to study vertebrate germ cell formation include their genetic tractability, the large numbers of progeny, and the easily manipulable genome, all of which make zebrafish an ideal system for studying the genetic regulators and cellular basis of germ cell formation and maintenance. Classical molecular biology techniques, including expression analysis through in situ hybridization and forward genetic screens, have laid the foundation for our understanding of germ cell development in zebrafish. In this chapter, we discuss some of these classic techniques, as well as recent cutting-edge methodologies that have improved our ability to visualize the process of germ cell specification and differentiation, and the tracking of specific molecules involved in these processes. Additionally, we discuss traditional and novel technologies for manipulating the zebrafish genome to identify new components through loss-of-function studies of putative germ cell regulators. Together with the numerous aforementioned advantages of zebrafish as a genetic model for studying development, we believe these new techniques will continue to advance zebrafish to the forefront for investigation of the molecular regulators of germ cell specification and germ line biology. PMID:27312489

The Diversity of Nanos Expression in Echinoderm Embryos Supports Different Mechanisms in Germ Cell Specification

PubMed Central

Fresques, Tara; Swartz, S. Zachary; Juliano, Celina; Morino, Yoshiaki; Kikuchi, Mani; Akasaka, Koji; Wada, Hiroshi; Yajima, Mamiko; Wessel, Gary M.

2016-01-01

Specification of the germ cell lineage is required for sexual reproduction in all animals. However, the timing and mechanisms of germ cell specification is remarkably diverse in animal development. Echinoderms, such as sea urchins and sea stars, are excellent model systems to study the molecular and cellular mechanisms that contribute to germ cell specification. In several echinoderm embryos tested, the germ cell factor Vasa accumulates broadly during early development and is restricted after gastrulation to cells that contribute to the germ cell lineage. In the sea urchin, however, the germ cell factor Vasa is restricted to a specific lineage by the 32-cell stage. We therefore hypothesized that the germ cell specification program in the sea urchin/Euechinoid lineage has evolved to an earlier developmental time point. To test this hypothesis we determined the expression pattern of a second germ cell factor, Nanos, in four out of five extant echinoderm clades. Here we find that Nanos mRNA does not accumulate until the blastula stage or later during the development of all other echinoderm embryos except those that belong to the Echinoid lineage. Instead, Nanos is expressed in a restricted domain at the 32–128 cell stage in Echinoid embryos. Our results support the model that the germ cell specification program underwent a heterochronic shift in the Echinoid lineage. A comparison of Echinoid and non-Echinoid germ cell specification mechanisms will contribute to our understanding of how these mechanisms have changed during animal evolution. PMID:27402572

Nuclear fragmentation of GCR-like ions: comparisons between data and PHITS

NASA Astrophysics Data System (ADS)

Zeitlin, Cary; Guetersloh, Stephen; Heilbronn, Lawrence; Miller, Jack; Sihver, Lembit; Mancusi, Davide; Fukumura, Aki; Iwata, Yoshi; Murakami, Takeshi

We present a summary of results from recent work in which we have compared nuclear fragmentation cross section data to predictions of the PHITS Monte Carlo simulation. The studies used beams of 12 C, 35 Cl, 40 Ar, 48 Ti, and 56 Fe at energies ranging from 290 MeV/nucleon to 1000 MeV/nucleon. Some of the data were obtained at the Brookhaven National Laboratory, others at the National Institute of Radiological Sciences in Japan. These energies and ion species are representative of the heavy ion component of the Galactic Cosmic Rays (GCR), which contribute significantly to the dose and dose equivalent that will be received by astronauts on deep-space missions. A critical need for NASA is the ability to accurately model the transport of GCR heavy ions through matter, including spacecraft walls, equipment racks, and other shielding materials, as well as through tissue. Nuclear interaction cross sections are of primary importance in the GCR transport problem. These interactions generally cause the incoming ion to break up (fragment) into one or more lighter ions, which continue approximately along the initial trajectory and with approximately the same velocity the incoming ion had prior to the interaction. Since the radiation dose delivered by a particle is proportional to the square of the quantity (charge/velocity), i.e., to (Z/β)2 , fragmentation reduces the dose (and, typically, dose equivalent) delivered by incident ions. The other mechanism by which dose can be reduced is ionization energy loss, which can lead to some particles stopping in the shielding. This is the conventional notion of shielding, but it is not applicable to human spaceflight, since the particles in the GCR tend to be highly energetic and because shielding must be relatively thin in order to keep overall mass as low as possible, keeping launch costs within reason. To support these goals, our group has systematically measured a large number of nuclear cross sections, intended to be used as either input to, or validation of, NASA transport models. A database containing over 200 charge-changing cross sections, and over 2000 fragment production cross sections, is nearing completion, with most results available online. In the past year, we have been investigating the PHITS (Particle and Heavy Ion Transport System) model of Niita et al. For purposes of modeling nuclear interactions, PHITS combines the Jet AA Microscopic Transport Model (JAM) hadron cascade model, the Jaeri Quantum Molecular Dynamics (JQMD) model, and the Generalized Evaporation Model (GEM). We will present detailed comparisons of our data to the cross sections and fragment angular distributions that arise from this model. The model contains some significant deficiencies, but, as we will show, also represents a significant advance over older, simpler models of fragmentation. 504b030414000600080000002100828abc13fa0000001c020000130000005b436f6e74656e745f54797065735d2e78

Surfing the wave, cycle, life history, and genes/proteins expressed by testicular germ cells. Part 4: intercellular bridges, mitochondria, nuclear envelope, apoptosis, ubiquitination, membrane/voltage-gated channels, methylation/acetylation, and transcription factors.

PubMed

Hermo, Louis; Pelletier, R-Marc; Cyr, Daniel G; Smith, Charles E

2010-04-01

As germ cells divide and differentiate from spermatogonia to spermatozoa, they share a number of structural and functional features that are common to all generations of germ cells and these features are discussed herein. Germ cells are linked to one another by large intercellular bridges which serve to move molecules and even large organelles from the cytoplasm of one cell to another. Mitochondria take on different shapes and features and topographical arrangements to accommodate their specific needs during spermatogenesis. The nuclear envelope and pore complex also undergo extensive modifications concomitant with the development of germ cell generations. Apoptosis is an event that is normally triggered by germ cells and involves many proteins. It occurs to limit the germ cell pool and acts as a quality control mechanism. The ubiquitin pathway comprises enzymes that ubiquitinate as well as deubiquitinate target proteins and this pathway is present and functional in germ cells. Germ cells express many proteins involved in water balance and pH control as well as voltage-gated ion channel movement. In the nucleus, proteins undergo epigenetic modifications which include methylation, acetylation, and phosphorylation, with each of these modifications signaling changes in chromatin structure. Germ cells contain specialized transcription complexes that coordinate the differentiation program of spermatogenesis, and there are many male germ cell-specific differences in the components of this machinery. All of the above features of germ cells will be discussed along with the specific proteins/genes and abnormalities to fertility related to each topic. Copyright 2009 Wiley-Liss, Inc.

Misexpression of cyclin D1 in embryonic germ cells promotes testicular teratoma initiation

PubMed Central

Lanza, Denise G.; Dawson, Emily P.; Rao, Priya; Heaney, Jason D.

2016-01-01

ABSTRACT Testicular teratomas result from anomalies in embryonic germ cell development. In the 129 family of inbred mouse strains, teratomas arise during the same developmental period that male germ cells normally enter G1/G0 mitotic arrest and female germ cells initiate meiosis (the mitotic:meiotic switch). Dysregulation of this switch associates with teratoma susceptibility and involves three germ cell developmental abnormalities seemingly critical for tumor initiation: delayed G1/G0 mitotic arrest, retention of pluripotency, and misexpression of genes normally restricted to embryonic female and adult male germ cells. One misexpressed gene, cyclin D1 (Ccnd1), is a known regulator of cell cycle progression and an oncogene in many tissues. Here, we investigated whether Ccnd1 misexpression in embryonic germ cells is a determinant of teratoma susceptibility in mice. We found that CCND1 localizes to teratoma-susceptible germ cells that fail to enter G1/G0 arrest during the mitotic:meiotic switch and is the only D-type cyclin misexpressed during this critical developmental time frame. We discovered that Ccnd1 deficiency in teratoma-susceptible mice significantly reduced teratoma incidence and suppressed the germ cell proliferation and pluripotency abnormalities associated with tumor initiation. Importantly, Ccnd1 expression was dispensable for somatic cell development and male germ cell specification and maturation in tumor-susceptible mice, implying that the mechanisms by which Ccnd1 deficiency reduced teratoma incidence were germ cell autonomous and specific to tumorigenesis. We conclude that misexpression of Ccnd1 in male germ cells is a key component of a larger pro-proliferative program that disrupts the mitotic:meiotic switch and predisposes 129 inbred mice to testicular teratocarcinogenesis. PMID:26901436

Palliative Care in Improving Quality of Life and Symptoms in Patients With Stage III-IV Pancreatic or Ovarian Cancer

ClinicalTrials.gov

2014-12-18

Recurrent Ovarian Epithelial Cancer; Recurrent Ovarian Germ Cell Tumor; Recurrent Pancreatic Cancer; Stage III Pancreatic Cancer; Stage IIIA Ovarian Epithelial Cancer; Stage IIIA Ovarian Germ Cell Tumor; Stage IIIB Ovarian Epithelial Cancer; Stage IIIB Ovarian Germ Cell Tumor; Stage IIIC Ovarian Epithelial Cancer; Stage IIIC Ovarian Germ Cell Tumor; Stage IV Ovarian Epithelial Cancer; Stage IV Ovarian Germ Cell Tumor; Stage IV Pancreatic Cancer

Piwi Is Required in Multiple Cell Types to Control Germline Stem Cell Lineage Development in the Drosophila Ovary

PubMed Central

Ma, Xing; Wang, Su; Do, Trieu; Song, Xiaoqing; Inaba, Mayu; Nishimoto, Yoshiya; Liu, Lu-ping; Gao, Yuan; Mao, Ying; Li, Hui; McDowell, William; Park, Jungeun; Malanowski, Kate; Peak, Allison; Perera, Anoja; Li, Hua; Gaudenz, Karin; Haug, Jeff; Yamashita, Yukiko; Lin, Haifan; Ni, Jian-quan; Xie, Ting

2014-01-01

The piRNA pathway plays an important role in maintaining genome stability in the germ line by silencing transposable elements (TEs) from fly to mammals. As a highly conserved piRNA pathway component, Piwi is widely expressed in both germ cells and somatic cells in the Drosophila ovary and is required for piRNA production in both cell types. In addition to its known role in somatic cap cells to maintain germline stem cells (GSCs), this study has demonstrated that Piwi has novel functions in somatic cells and germ cells of the Drosophila ovary to promote germ cell differentiation. Piwi knockdown in escort cells causes a reduction in escort cell (EC) number and accumulation of undifferentiated germ cells, some of which show active BMP signaling, indicating that Piwi is required to maintain ECs and promote germ cell differentiation. Simultaneous knockdown of dpp, encoding a BMP, in ECs can partially rescue the germ cell differentiation defect, indicating that Piwi is required in ECs to repress dpp. Consistent with its key role in piRNA production, TE transcripts increase significantly and DNA damage is also elevated in the piwi knockdown somatic cells. Germ cell-specific knockdown of piwi surprisingly causes depletion of germ cells before adulthood, suggesting that Piwi might control primordial germ cell maintenance or GSC establishment. Finally, Piwi inactivation in the germ line of the adult ovary leads to gradual GSC loss and germ cell differentiation defects, indicating the intrinsic role of Piwi in adult GSC maintenance and differentiation. This study has revealed new germline requirement of Piwi in controlling GSC maintenance and lineage differentiation as well as its new somatic function in promoting germ cell differentiation. Therefore, Piwi is required in multiple cell types to control GSC lineage development in the Drosophila ovary. PMID:24658126

Extracranial Germ Cell Tumors—Health Professional Version

Cancer.gov

Extracranial germ cell tumors (GCTs) arise from primordial germ cells, which migrate during embryogenesis from the yolk sac to the gonads. Childhood extracranial GCTs can be divided into the following two types: gonadal, and extragonadal. Find evidence-based information on extracranial germ cell tumors treatment.

Identification of Potential Germ-Cell Mutagens

EPA Science Inventory

The existence of agents that can induce germ-cell mutations in experimental systems has been recognized since 1927 with the discovery of the ability of X-rays to induce such mutations in Drosophila. Various rodent-based germ-cell mutation assays have been developed, and ~50 germ...

Maternal dazap2 Regulates Germ Granules by Counteracting Dynein in Zebrafish Primordial Germ Cells.

PubMed

Forbes, Meredyth M; Rothhämel, Sophie; Jenny, Andreas; Marlow, Florence L

2015-07-07

Primordial germ cells (PGCs) are the stem cells of the germline. Generally, germline induction occurs via zygotic factors or the inheritance of maternal determinants called germ plasm (GP). GP is packaged into ribonucleoprotein complexes within oocytes and later promotes the germline fate in embryos. Once PGCs are specified by either mechanism, GP components localize to perinuclear granular-like structures. Although components of zebrafish PGC germ granules have been studied, the maternal factors regulating their assembly and contribution to germ cell development are unknown. Here, we show that the scaffold protein Dazap2 binds to Bucky ball, an essential regulator of oocyte polarity and GP assembly, and colocalizes with the GP in oocytes and in PGCs. Mutational analysis revealed a requirement for maternal Dazap2 (MDazap2) in germ-granule maintenance. Through molecular epistasis analyses, we show that MDazap2 is epistatic to Tdrd7 and maintains germ granules in the embryonic germline by counteracting Dynein activity. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Germ Cell-less Promotes Centrosome Segregation to Induce Germ Cell Formation.

PubMed

Lerit, Dorothy A; Shebelut, Conrad W; Lawlor, Kristen J; Rusan, Nasser M; Gavis, Elizabeth R; Schedl, Paul; Deshpande, Girish

2017-01-24

The primordial germ cells (PGCs) specified during embryogenesis serve as progenitors to the adult germline stem cells. In Drosophila, the proper specification and formation of PGCs require both centrosomes and germ plasm, which contains the germline determinants. Centrosomes are microtubule (MT)-organizing centers that ensure the faithful segregation of germ plasm into PGCs. To date, mechanisms that modulate centrosome behavior to engineer PGC development have remained elusive. Only one germ plasm component, Germ cell-less (Gcl), is known to play a role in PGC formation. Here, we show that Gcl engineers PGC formation by regulating centrosome dynamics. Loss of gcl leads to aberrant centrosome separation and elaboration of the astral MT network, resulting in inefficient germ plasm segregation and aborted PGC cellularization. Importantly, compromising centrosome separation alone is sufficient to mimic the gcl loss-of-function phenotypes. We conclude Gcl functions as a key regulator of centrosome separation required for proper PGC development. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Drosophila germ granules are structured and contain homotypic mRNA clusters

PubMed Central

Trcek, Tatjana; Grosch, Markus; York, Andrew; Shroff, Hari; Lionnet, Timothée; Lehmann, Ruth

2015-01-01

Germ granules, specialized ribonucleoprotein particles, are a hallmark of all germ cells. In Drosophila, an estimated 200 mRNAs are enriched in the germ plasm, and some of these have important, often conserved roles in germ cell formation, specification, survival and migration. How mRNAs are spatially distributed within a germ granule and whether their position defines functional properties is unclear. Here we show, using single-molecule FISH and structured illumination microscopy, a super-resolution approach, that mRNAs are spatially organized within the granule whereas core germ plasm proteins are distributed evenly throughout the granule. Multiple copies of single mRNAs organize into ‘homotypic clusters' that occupy defined positions within the center or periphery of the granule. This organization, which is maintained during embryogenesis and independent of the translational or degradation activity of mRNAs, reveals new regulatory mechanisms for germ plasm mRNAs that may be applicable to other mRNA granules. PMID:26242323

Optimal shielding thickness for galactic cosmic ray environments

NASA Astrophysics Data System (ADS)

Slaba, Tony C.; Bahadori, Amir A.; Reddell, Brandon D.; Singleterry, Robert C.; Clowdsley, Martha S.; Blattnig, Steve R.

2017-02-01

Models have been extensively used in the past to evaluate and develop material optimization and shield design strategies for astronauts exposed to galactic cosmic rays (GCR) on long duration missions. A persistent conclusion from many of these studies was that passive shielding strategies are inefficient at reducing astronaut exposure levels and the mass required to significantly reduce the exposure is infeasible, given launch and associated cost constraints. An important assumption of this paradigm is that adding shielding mass does not substantially increase astronaut exposure levels. Recent studies with HZETRN have suggested, however, that dose equivalent values actually increase beyond ∼20 g/cm2 of aluminum shielding, primarily as a result of neutron build-up in the shielding geometry. In this work, various Monte Carlo (MC) codes and 3DHZETRN are evaluated in slab geometry to verify the existence of a local minimum in the dose equivalent versus aluminum thickness curve near 20 g/cm2. The same codes are also evaluated in polyethylene shielding, where no local minimum is observed, to provide a comparison between the two materials. Results are presented so that the physical interactions driving build-up in dose equivalent values can be easily observed and explained. Variation of transport model results for light ions (Z ≤ 2) and neutron-induced target fragments, which contribute significantly to dose equivalent for thick shielding, is also highlighted and indicates that significant uncertainties are still present in the models for some particles. The 3DHZETRN code is then further evaluated over a range of related slab geometries to draw closer connection to more realistic scenarios. Future work will examine these related geometries in more detail.

Optimal shielding thickness for galactic cosmic ray environments.

PubMed

Slaba, Tony C; Bahadori, Amir A; Reddell, Brandon D; Singleterry, Robert C; Clowdsley, Martha S; Blattnig, Steve R

2017-02-01

Models have been extensively used in the past to evaluate and develop material optimization and shield design strategies for astronauts exposed to galactic cosmic rays (GCR) on long duration missions. A persistent conclusion from many of these studies was that passive shielding strategies are inefficient at reducing astronaut exposure levels and the mass required to significantly reduce the exposure is infeasible, given launch and associated cost constraints. An important assumption of this paradigm is that adding shielding mass does not substantially increase astronaut exposure levels. Recent studies with HZETRN have suggested, however, that dose equivalent values actually increase beyond ∼20g/cm 2 of aluminum shielding, primarily as a result of neutron build-up in the shielding geometry. In this work, various Monte Carlo (MC) codes and 3DHZETRN are evaluated in slab geometry to verify the existence of a local minimum in the dose equivalent versus aluminum thickness curve near 20g/cm 2 . The same codes are also evaluated in polyethylene shielding, where no local minimum is observed, to provide a comparison between the two materials. Results are presented so that the physical interactions driving build-up in dose equivalent values can be easily observed and explained. Variation of transport model results for light ions (Z ≤ 2) and neutron-induced target fragments, which contribute significantly to dose equivalent for thick shielding, is also highlighted and indicates that significant uncertainties are still present in the models for some particles. The 3DHZETRN code is then further evaluated over a range of related slab geometries to draw closer connection to more realistic scenarios. Future work will examine these related geometries in more detail. Published by Elsevier Ltd.

Numerical Study of the Generation of Linear Energy Transfer Spectra for Space Radiation Applications

NASA Technical Reports Server (NTRS)

Badavi, Francis F.; Wilson, John W.; Hunter, Abigail

2005-01-01

In analyzing charged particle spectra in space due to galactic cosmic rays (GCR) and solar particle events (SPE), the conversion of particle energy spectra into linear energy transfer (LET) distributions is a convenient guide in assessing biologically significant components of these spectra. The mapping of LET to energy is triple valued and can be defined only on open energy subintervals where the derivative of LET with respect to energy is not zero. Presented here is a well-defined numerical procedure which allows for the generation of LET spectra on the open energy subintervals that are integrable in spite of their singular nature. The efficiency and accuracy of the numerical procedures is demonstrated by providing examples of computed differential and integral LET spectra and their equilibrium components for historically large SPEs and 1977 solar minimum GCR environments. Due to the biological significance of tissue, all simulations are done with tissue as the target material.

Quiet-Time Spectra and Abundances of Energetic Particles During the 1996 Solar Minimum

NASA Technical Reports Server (NTRS)

Reames, Donald V.

1999-01-01

We report the energy spectra and abundances of ions with atomic number, Z, in the interval Z is greater than or equal to 2 and Z is less than or equal to 36 and energies approximately 3-20 MeV/amu for solar and interplanetary quiet periods between 1994 November and 1998 April as measured by the large-geometry Low Energy Matrix Telescope (LEMT) telescope on the Wind spacecraft near Earth. The energy spectra show the presence of galactic (GCR) and "anomalous" cosmic ray (ACR) components, depending on the element. ACR components are reported for Mg and Si for the first time at 1 AU and the previous observation of S and Ar is confirmed. However, only GCR components are clearly apparent for the elements Ca, Ti, Cr, Fe, as well as for C. New limits are placed on a possible ACR contribution for other elements, including Kr.

Quiet-Time Spectra and Abundances of Energetic Particles During the 1996 Solar Minimum

NASA Technical Reports Server (NTRS)

Reames, Donald V.

1998-01-01

This report concerns the energy spectra and abundances of ions with atomic number, Z, in the interval 2 greater than or equal to Z and Z less than or equal to 36 and energies approximately 3-20 MeV/amu for solar and interplanetary quiet periods between November 1994 and April 1998 as measured by the large-geometry LEMT telescope on the Wind spacecraft near Earth. The energy spectra show the presence of galactic (GCR) and 'anomalous' cosmic ray (ACR) components, depending on the element. ACR components are reported for Mg and Si for the first time at 1 AU and the previous observation of S and Ar is confirmed. However, only GCR components are clearly apparent for the elements Ca, Ti, Cr, Fe, as well as for C. New limits are placed on a possible ACR contribution for other elements, including Kr.

Preliminary Design of a Galactic Cosmic Ray Shielding Materials Testbed for the International Space Station

NASA Technical Reports Server (NTRS)

Gaier, James R.; Berkebile, Stephen; Sechkar, Edward A.; Panko, Scott R.

2012-01-01

The preliminary design of a testbed to evaluate the effectiveness of galactic cosmic ray (GCR) shielding materials, the MISSE Radiation Shielding Testbed (MRSMAT) is presented. The intent is to mount the testbed on the Materials International Space Station Experiment-X (MISSE-X) which is to be mounted on the International Space Station (ISS) in 2016. A key feature is the ability to simultaneously test nine samples, including standards, which are 5.25 cm thick. This thickness will enable most samples to have an areal density greater than 5 g/sq cm. It features a novel and compact GCR telescope which will be able to distinguish which cosmic rays have penetrated which shielding material, and will be able to evaluate the dose transmitted through the shield. The testbed could play a pivotal role in the development and qualification of new cosmic ray shielding technologies.

Cosmic Ray Modulation in the Outer Heliosphere During the Minimum of Solar Cycle 23/24

NASA Technical Reports Server (NTRS)

Adams, James H., Jr.; Florinski, V.; Washimi, H.; Pogorelov, N. V.

2011-01-01

We report a next generation model of galactic cosmic ray (GCR) transport in the three dimensional heliosphere. Our model is based on an accurate three-dimensional representation of the heliospheric interface. This representation is obtained by taking into account the interaction between partially ionized, magnetized plasma flows of the solar wind and the local interstellar medium. Our model reveals that after entering the heliosphere GCRs are stored in the heliosheath for several years. The preferred GCR entry locations are near the nose of the heliopause and at high latitudes. Low-energy (hundreds of MeV) galactic ions observed in the heliosheath have spent, on average, a longer time in the solar wind than those observed in the inner heliosphere, which would explain their cooled-off spectra at these energies. We also discuss radial gradients in the heliosheath and the implications for future Voyager observations.

Abstracts for student symposium

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

Goldman, B.

Lawrence Livermore National Laboratory Science and Engineering Research Semester (SERS) students are participants in a national program sponsored by the DOE Office of Energy Research. Presented topics from Fall 1993 include: Laser glass, wiring codes, lead in food and food containers, chromium removal from ground water, fiber optic sensors for ph measurement, CFC replacement, predator/prey simulation, detection of micronuclei in germ cells, DNA conformation, stimulated brillouin scattering, DNA sequencing, evaluation of education programs, neural network analysis of nuclear glass, lithium ion batteries, Indonesian snails, optical switching systems, and photoreceiver design. Individual papers are indexed separately on the Energy Data Base.

Epigenetic Mechanisms of Transmission of Metabolic Disease across Generations.

PubMed

Sales, Vicencia Micheline; Ferguson-Smith, Anne C; Patti, Mary-Elizabeth

2017-03-07

Both human and animal studies indicate that environmental exposures experienced during early life can robustly influence risk for adult disease. Moreover, environmental exposures experienced by parents during either intrauterine or postnatal life can also influence the health of their offspring, thus initiating a cycle of disease risk across generations. In this Perspective, we focus on epigenetic mechanisms in germ cells, including DNA methylation, histone modification, and non-coding RNAs, which collectively may provide a non-genetic molecular legacy of prior environmental exposures and influence transcriptional regulation, developmental trajectories, and adult disease risk in offspring. Copyright © 2017 Elsevier Inc. All rights reserved.

In Vitro Germ Cell Differentiation from Cynomolgus Monkey Embryonic Stem Cells

PubMed Central

Yamauchi, Kaori; Hasegawa, Kouichi; Chuma, Shinichiro; Nakatsuji, Norio; Suemori, Hirofumi

2009-01-01

Background Mouse embryonic stem (ES) cells can differentiate into female and male germ cells in vitro. Primate ES cells can also differentiate into immature germ cells in vitro. However, little is known about the differentiation markers and culture conditions for in vitro germ cell differentiation from ES cells in primates. Monkey ES cells are thus considered to be a useful model to study primate gametogenesis in vitro. Therefore, in order to obtain further information on germ cell differentiation from primate ES cells, this study examined the ability of cynomolgus monkey ES cells to differentiate into germ cells in vitro. Methods and Findings To explore the differentiation markers for detecting germ cells differentiated from ES cells, the expression of various germ cell marker genes was examined in tissues and ES cells of the cynomolgus monkey (Macaca fascicularis). VASA is a valuable gene for the detection of germ cells differentiated from ES cells. An increase of VASA expression was observed when differentiation was induced in ES cells via embryoid body (EB) formation. In addition, the expression of other germ cell markers, such as NANOS and PIWIL1 genes, was also up-regulated as the EB differentiation progressed. Immunocytochemistry identified the cells expressing stage-specific embryonic antigen (SSEA) 1, OCT-4, and VASA proteins in the EBs. These cells were detected in the peripheral region of the EBs as specific cell populations, such as SSEA1-positive, OCT-4-positive cells, OCT-4-positive, VASA-positive cells, and OCT-4-negative, VASA-positive cells. Thereafter, the effect of mouse gonadal cell-conditioned medium and growth factors on germ cell differentiation from monkey ES cells was examined, and this revealed that the addition of BMP4 to differentiating ES cells increased the expression of SCP1, a meiotic marker gene. Conclusion VASA is a valuable gene for the detection of germ cells differentiated from ES cells in monkeys, and the identification and characterization of germ cells derived from ES cells are possible by using reported germ cell markers in vivo, including SSEA1, OCT-4, and VASA, in vitro as well as in vivo. These findings are thus considered to help elucidate the germ cell developmental process in primates. PMID:19399191

Extragonadal Germ Cell Tumors—Health Professional Version

Cancer.gov

Extragonadal germ cell tumors are rare and account for only a small percentage of all germ cell tumors. However, the true incidence of these tumors may be higher than originally thought because of failure to diagnose them properly. Find evidence-based information on extragonadal germ cell tumors treatment.

Extraction and characterization of corn germ proteins

USDA-ARS?s Scientific Manuscript database

Our study was conducted to develop methods to extract corn germ protein economically and characterize and identify potential applications of the recovered protein. Protein was extracted from both wet germ and finished (dried) germ using 0.1M NaCl as solvent. The method involved homogenization, sti...

Improvement of dry fractionation ethanol fermentation by partial germ supplementation

USDA-ARS?s Scientific Manuscript database

Ethanol fermentation of dry fractionated grits (corn endosperm pieces) containing different levels of germ was studied using the dry grind process. Partial removal of germ fraction allows for marketing the germ fraction and potentially more efficient fermentation. Grits obtained from a dry milling p...

Description of Light Ion Production Cross Sections and Fluxes on the Mars Surface using the QMSFRG Model

NASA Technical Reports Server (NTRS)

Cucinotta, Francis A.; Kim, Myung-Hee; Schneider, Irene; Hassler, Donald M.

2006-01-01

The atmosphere of Mars significantly attenuates the heavy ion component of the primary galactic cosmic rays (GCR), however increases the fluence of secondary light ions (neutrons, and hydrogen and helium isotopes) because of particle production processes. We describe results of the quantum multiple scattering fragmentation (QMSFRG) model for the production of light nuclei through the distinct mechanisms of nuclear abrasion and ablation, coalescence, and cluster knockout. The QMSFRG model is shown to be in excellent agreement with available experimental data for nuclear fragmentation cross sections. We use the QMSFRG model and the space radiation transport code, HZETRN to make predictions of the light particle environment on the Martian surface at solar minimum and maximum. The radiation assessment detector (RAD) experiment will be launched in 2009 as part of the Mars Science Laboratory (MSL). We make predictions of the expected results for time dependent count-rates to be observed by RAD experiment. Finally, we consider sensitivity assessments of the impact of the Martian atmospheric composition on particle fluxes at the surface.

Improved Spacecraft Materials for Radiation Shielding

NASA Technical Reports Server (NTRS)

Wilson, J. W.; Shinn, J. L.; Singleterry, R. C.; Tai, H.; Thibeault, S. A.; Simonsen, L. C.; Cucinotta, F. A.; Miller, J.

1999-01-01

In the execution of this proposal, we will first examine current and developing spacecraft materials and evaluate their ability to attenuate adverse biological mutational events in mammalian cell systems and reduce the rate of cancer induction in mice harderian glands as a measure of their protective qualities. The HZETRN code system will be used to generate a database on GCR attenuation in each material. If a third year of funding is granted, the most promising and mission-specific materials will be used to study the impact on mission cost for a typical Mars mission scenario as was planned in our original two year proposal at the original funding level. The most promising candidate materials will be further tested as to their transmission characteristics in Fe and Si ion beams to evaluate the accuracy of the HZETRN transmission factors. Materials deemed critical to mission success may also require testing as well as materials developed by industry for their radiation protective qualities (e.g., Physical Sciences Inc.) A study will be made of designing polymeric materials and composite materials with improved radiation shielding properties as well as the possible improvement of mission-specific materials.

From Young Children's Ideas about Germs to Ideas Shaping a Learning Environment

NASA Astrophysics Data System (ADS)

Ergazaki, Marida; Saltapida, Konstantina; Zogza, Vassiliki

2010-11-01

This paper is concerned with highlighting young children’s ideas about the nature, location and appearance of germs, as well as their reasoning strands about germs’ ontological category and biological functions. Moreover, it is concerned with exploring how all these could be taken into account for shaping a potentially fruitful learning environment. Conducting individual, semi-structured interviews with 35 preschoolers (age 4.5-5.5) of public kindergartens in the broader area of Patras, we attempted to trace their ideas about what germs are, where they may be found, whether they are good or bad and living or non-living and how they might look like in a drawing. Moreover, children were required to attribute a series of biological functions to dogs, chairs and germs, and finally to create a story with germs holding a key-role. The analysis of our qualitative data within the “NVivo” software showed that the informants make a strong association of germs with health and hygiene issues, locate germs mostly in our body and the external environment, are not familiar with the ‘good germs’-idea, and draw germs as ‘human-like’, ‘animal-like’ or ‘abstract’ entities. Moreover, they have significant difficulties not only in employing biological functions as criteria for classifying germs in the category of ‘living’, but also in just attributing such functions to germs using a warrant. Finally, the shift from our findings to a 3-part learning environment aiming at supporting preschoolers in refining their initial conceptualization of germs is thoroughly discussed in the paper.

The diversity of nanos expression in echinoderm embryos supports different mechanisms in germ cell specification.

PubMed

Fresques, Tara; Swartz, Steven Zachary; Juliano, Celina; Morino, Yoshiaki; Kikuchi, Mani; Akasaka, Koji; Wada, Hiroshi; Yajima, Mamiko; Wessel, Gary M

2016-07-01

Specification of the germ cell lineage is required for sexual reproduction in all animals. However, the timing and mechanisms of germ cell specification is remarkably diverse in animal development. Echinoderms, such as sea urchins and sea stars, are excellent model systems to study the molecular and cellular mechanisms that contribute to germ cell specification. In several echinoderm embryos tested, the germ cell factor Vasa accumulates broadly during early development and is restricted after gastrulation to cells that contribute to the germ cell lineage. In the sea urchin, however, the germ cell factor Vasa is restricted to a specific lineage by the 32-cell stage. We therefore hypothesized that the germ cell specification program in the sea urchin/Euechinoid lineage has evolved to an earlier developmental time point. To test this hypothesis we determined the expression pattern of a second germ cell factor, Nanos, in four out of five extant echinoderm clades. Here we find that Nanos mRNA does not accumulate until the blastula stage or later during the development of all other echinoderm embryos except those that belong to the Echinoid lineage. Instead, Nanos is expressed in a restricted domain at the 32-128 cell stage in Echinoid embryos. Our results support the model that the germ cell specification program underwent a heterochronic shift in the Echinoid lineage. A comparison of Echinoid and non-Echinoid germ cell specification mechanisms will contribute to our understanding of how these mechanisms have changed during animal evolution. © 2016 Wiley Periodicals, Inc.

Extracranial Germ Cell Tumors—Patient Version

Cancer.gov

Extracranial germ cell tumors are tumors that develop from germ cells (fetal cells that give rise to sperm and eggs) and can form in many parts of the body. They are most common in teenagers and can often be cured. Start here to find information on extracranial germ cell tumors treatment.

DNA Analysis in Samples From Younger Patients With Germ Cell Tumors and Their Parents or Siblings

ClinicalTrials.gov

2017-10-05

Childhood Malignant Ovarian Germ Cell Tumor; Childhood Malignant Testicular Germ Cell Tumor; Ovarian Choriocarcinoma; Ovarian Embryonal Carcinoma; Ovarian Mixed Germ Cell Tumor; Ovarian Teratoma; Ovarian Yolk Sac Tumor; Testicular Choriocarcinoma; Testicular Embryonal Carcinoma; Testicular Seminoma; Testicular Teratoma; Testicular Yolk Sac Tumor

Probabilistic Assessment of Cancer Risk from Solar Particle Events

NASA Astrophysics Data System (ADS)

Kim, Myung-Hee Y.; Cucinotta, Francis A.

For long duration missions outside of the protection of the Earth's magnetic field, space radi-ation presents significant health risks including cancer mortality. Space radiation consists of solar particle events (SPEs), comprised largely of medium energy protons (less than several hundred MeV); and galactic cosmic ray (GCR), which include high energy protons and heavy ions. While the frequency distribution of SPEs depends strongly upon the phase within the solar activity cycle, the individual SPE occurrences themselves are random in nature. We es-timated the probability of SPE occurrence using a non-homogeneous Poisson model to fit the historical database of proton measurements. Distributions of particle fluences of SPEs for a specified mission period were simulated ranging from its 5th to 95th percentile to assess the cancer risk distribution. Spectral variability of SPEs was also examined, because the detailed energy spectra of protons are important especially at high energy levels for assessing the cancer risk associated with energetic particles for large events. We estimated the overall cumulative probability of GCR environment for a specified mission period using a solar modulation model for the temporal characterization of the GCR environment represented by the deceleration po-tential (φ). Probabilistic assessment of cancer fatal risk was calculated for various periods of lunar and Mars missions. This probabilistic approach to risk assessment from space radiation is in support of mission design and operational planning for future manned space exploration missions. In future work, this probabilistic approach to the space radiation will be combined with a probabilistic approach to the radiobiological factors that contribute to the uncertainties in projecting cancer risks.

Probabilistic Assessment of Cancer Risk from Solar Particle Events

NASA Technical Reports Server (NTRS)

Kim, Myung-Hee Y.; Cucinotta, Francis A.

2010-01-01

For long duration missions outside of the protection of the Earth s magnetic field, space radiation presents significant health risks including cancer mortality. Space radiation consists of solar particle events (SPEs), comprised largely of medium energy protons (less than several hundred MeV); and galactic cosmic ray (GCR), which include high energy protons and heavy ions. While the frequency distribution of SPEs depends strongly upon the phase within the solar activity cycle, the individual SPE occurrences themselves are random in nature. We estimated the probability of SPE occurrence using a non-homogeneous Poisson model to fit the historical database of proton measurements. Distributions of particle fluences of SPEs for a specified mission period were simulated ranging from its 5 th to 95th percentile to assess the cancer risk distribution. Spectral variability of SPEs was also examined, because the detailed energy spectra of protons are important especially at high energy levels for assessing the cancer risk associated with energetic particles for large events. We estimated the overall cumulative probability of GCR environment for a specified mission period using a solar modulation model for the temporal characterization of the GCR environment represented by the deceleration potential (^). Probabilistic assessment of cancer fatal risk was calculated for various periods of lunar and Mars missions. This probabilistic approach to risk assessment from space radiation is in support of mission design and operational planning for future manned space exploration missions. In future work, this probabilistic approach to the space radiation will be combined with a probabilistic approach to the radiobiological factors that contribute to the uncertainties in projecting cancer risks.

Division or department: a microeconomic analysis.

PubMed

Mar, Philip L; Yu, Robert A; Yu, Jack C

2011-06-01

In this article, the authors present a microeconomic analysis of the effects of the administrative status on plastic surgery units within academic medical centers, comparing the departmental versus subdepartmental status. The objectives are to introduce decision-making tools of microeconomics and use them to explore the potential effects of administrative status on academic plastic surgery services. Real financial data over a decade were used to construct total cost (TC), average total cost (ATC), and total revenue (TR) curves. From these, the authors derive the efficiency scale and express the fiscal performance by examining profitability, and the commonly used ATC curve. Mathematical modeling is then used to examine the effects of departmental versus subdepartmental status, assuming that (1) a plastic surgery unit exists in a competitive market; and (2) TR > TC for the plastic surgery unit to self-sustain in the long term. The variables considered are total clinical production (Q), gross collection rates (GCR), personnel cost, and departmental tax. The sustainability (Q against GCR) is a hyperbolic curve with Q × GCR = TC at break-even. The TC/TR = f(TR) curve resembles the ATC curve. Sectional versus departmental status for a plastic surgery service in an academic medical center depends greatly on the shape of their TC/TR = f(TR) curve. With most competing clinical units within the same academic medical center having departmental status, and most competing private surgeons having no institutional "taxes," the essential requirement for academic medical center plastic surgery services is to ensure that their TC/TR = f(TR) curve is comparable to that of their competitors.

Measurements of Forbush decreases at Mars: both by MSL on ground and by MAVEN in orbit

NASA Astrophysics Data System (ADS)

Guo, J.; Lillis, R. J.; Wimmer-Schweingruber, R. F.; Posner, A.; Halekas, J. S.; Zeitlin, C.; Hassler, D.; Lundt, N.; Simonson, P.; Lee, C. O.; Appel, J. K.; Boehm, E.; Boettcher, S. I.; Burmeister, S.; Brinza, D. E.; Cucinotta, F.; Ehresmann, B.; Lohf, H.; Martin-Garcia, C.; Matthiae, D.; Rafkin, S. C.; Reitz, G.; weigle, G., II

2017-12-01

The Radiation Assessment Detector (RAD), on board Mars Science Laboratory's (MSL) rover Curiosity, has been measuring the ground level particle fluxes along with the radiation dose rate at the surface of Mars since August 2012. Similar to neutron monitors at Earth, RAD sees many Forbush decreases (FDs) in the galactic cosmic ray (GCR) induced surface fluxes and dose rates. These FDs are associated with coronal mass ejections (CMEs) and/or streaming/corotating interaction regions (SIRs/CIRs). Orbiting above the Martian atmosphere, the Mars Atmosphere and Volatile EvolutioN (MAVEN) spacecraft has also been monitoring space weather conditions at Mars since its arrival in September 2014. The penetrating particle flux channel in the Solar Energetic Particle (SEP) instrument aboard can also be employed to detect FDs. For the first time, we study the statistics and properties of a list of FDs observed in-situ at Mars, seen both on the surface by MSL/RAD and in orbit detected by the MAVEN/SEP instrument. Such a list of FDs can be used for studying ICME propagations and SIR evolutions through the inner-heliosphere. The magnitudes of different FDs can be well-fitted by a power-law distribution. The systematic difference between the magnitudes of the FDs within and outside the Martian atmosphere may be attributed to the energy-dependent modulation of the GCR particles by not only the pass-by ICMEs/SIRs but also the Martian atmosphere. Such an effect has been modeled via transporting particles of differently modulated GCR spectra through the Martian atmosphere.

Radiation Measured for Chinese Satellite SJ-10 Space Mission

NASA Astrophysics Data System (ADS)

Zhou, Dazhuang; Sun, Yeqing; Zhang, Binquan; Zhang, Shenyi; Sun, Yueqiang; Liang, Jinbao; Zhu, Guangwu; Jing, Tao; Yuan, Bin; Zhang, Huanxin; Zhang, Meng; Wang, Wei; Zhao, Lei

2018-02-01

Space biological effects are mainly a result of space radiation particles with high linear energy transfer (LET); therefore, accurate measurement of high LET space radiation is vital. The radiation in low Earth orbits is composed mainly of high-energy galactic cosmic rays (GCRs), solar energetic particles, particles of radiation belts, the South Atlantic Anomaly, and the albedo neutrons and protons scattered from the Earth's atmosphere. CR-39 plastic nuclear track detectors sensitive to high LET are the best passive detectors to measure space radiation. The LET method that employs CR-39 can measure all the radiation LET spectra and quantities. CR-39 detectors can also record the incident directions and coordinates of GCR heavy ions that pass through both CR-39 and biosamples, and the impact parameter, the distance between the particle's incident point and the seed's spore, can then be determined. The radiation characteristics and impact parameter of GCR heavy ions are especially beneficial for in-depth research regarding space radiation biological effects. The payload returnable satellite SJ-10 provided an excellent opportunity to investigate space radiation biological effects with CR-39 detectors. The space bio-effects experiment was successfully conducted on board the SJ-10 satellite. This paper introduces space radiation in low Earth orbits and the LET method in radiation-related research and presents the results of nuclear tracks and biosamples hitting distributions of GCR heavy ions, the radiation LET spectra, and the quantities measured for the SJ-10 space mission. The SJ-10 bio-experiment indicated that radiation may produce significant bio-effects.

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%.

Interplanetary Magnetic Field Turbulence and Rigidity Spectrum of the Galactic Cosmic Rays Intensity Variation (1969-2011)

NASA Astrophysics Data System (ADS)

Siluszyk, M.; Alania, M. V.; Iskra, K.; Miernicki, S.

2018-01-01

The present study investigates the relation between the rigidity R spectrum exponent γ of the galactic cosmic rays (GCR) flux changes (δD(R)/D(R) ∝ R-γ) and the exponents νy and νz of the power spectral density of the By and Bz components of the heliospheric magnetic field (HMF) fluctuations. Two parameters have been introduced: (1) the exponent γ demonstrating the rigidity dependence of long-term changes of GCR flux on solar activity (SA) and (2) the exponents νy and νz signifying the state of turbulence which is divided of the By and Bz components. This study considers the period of time between 1969 and 2011 divided into four subperiods, according to the solar global magnetic field polarities: (I) 1969-1979, (A > 0) (positive polarity magnetic field lines are directed away from the Sun's northern hemisphere); (II) 1980-1988, (A < 0) (negative polarity magnetic field lines are directed toward the Sun's northern hemisphere); (III) 1991-2001, (A > 0) and (IV) 2002-2011, (A < 0). The paper finds that temporal changes of the resonant frequency (fres) of GCR protons in heliospheric magnetic field turbulence in relation to SA are mainly caused by variations of the induction of B components from year to year, while the contribution of the solar wind speed remains insignificant. The analyses of the four subperiods show that γ increases and νy and νz decrease in the periods of increased SA, and conversely, the γ decreases and νy and νz increase in the periods of reduced SA. The study concludes that the exponents γ, and νy and νz can be considered as important indices (proxies) for research on GCR transport in the heliosphere.

Primordial Germ Cells in Mice

PubMed Central

Saitou, Mitinori; Yamaji, Masashi

2012-01-01

Germ cell development creates totipotency through genetic as well as epigenetic regulation of the genome function. Primordial germ cells (PGCs) are the first germ cell population established during development and are immediate precursors for both the oocytes and spermatogonia. We here summarize recent findings regarding the mechanism of PGC development in mice. We focus on the transcriptional and signaling mechanism for PGC specification, potential pluripotency, and epigenetic reprogramming in PGCs and strategies for the reconstitution of germ cell development using pluripotent stem cells in culture. Continued studies on germ cell development may lead to the generation of totipotency in vitro, which should have a profound influence on biological science as well as on medicine. PMID:23125014

Interpretation of TEPC Measurements in Space Flights for Radiation Monitoring

NASA Technical Reports Server (NTRS)

Kim, Myung-Hee Y.; Nikjoo, Hooshang; Dicello, John F.; Pisacane, Vincent; Cucinotta, Francis A.

2007-01-01

For the proper interpretation of radiation data measured in space, the results of integrated radiation transport models were compared with the tissue equivalent proportional counter (TEPC) measurements. TEPC is a simple, time-dependent approach to radiation monitoring for astronauts on board the International Space Station. Another and a newer approach to microdosimetry is the use of silicon-on-insulator (SOI) technology launched on the MidSTAR-1 mission in low Earth orbit (LEO). In the radiation protection practice, the average quality factor of a radiation field is defined as a function of linear energy transfer (LET), Qave(LET). However, TEPC measures the average quality factor as a function of the lineal energy y, Qave(y), defined as the average energy deposition in a volume divided by the average chord length of the volume. The deviation of y from LET is caused by energy straggling, delta-ray escape or entry, and nuclear fragments produced in the detector volume. The response distribution functions of the wall-less and walled TEPCs were calculated from Monte-Carlo track simulations. Using an integrated space radiation model (which includes the transport codes HZETRN and BRYNTRN, and the quantum nuclear interaction model QMSFRG) and the resultant response distribution functions from Monte-Carlo track simulations, we compared model calculations with the walled-TEPC measurements from NASA missions in LEO and made predictions for the lunar and the Mars missions. Good agreement was found for Qave(y) between the model and measured spectra from past NASA missions. The Qave(y) values for the trapped or the solar protons ranged from 1.9-2.5. This over-estimates the Qave(LET) values which ranged from 1.4-1.6. Both quantities increase with shield thickness due to nuclear fragmentation. The Qave(LET) for the complete GCR spectra was found to be 3.5-4.5, while flight TEPCs measured 2.9-3.4 for Qave(y). The GCR values are decreasing with the shield thickness. Our analysis of the measurements of TEPCs can be used for a proper interpretation of observed data of monitoring the space radiation environment.

DAZL is essential for stress granule formation implicated in germ cell survival upon heat stress.

PubMed

Kim, Byunghyuk; Cooke, Howard J; Rhee, Kunsoo

2012-02-01

Mammalian male germ cells should be maintained below body temperature for proper development. Here, we investigated how male germ cells respond to heat stress. A short exposure of mouse testes to core body temperature induced phosphorylation of eIF2α and the formation of stress granules (SGs) in male germ cells. We observed that DAZL, a germ cell-specific translational regulator, was translocated to SGs upon heat stress. Furthermore, SG assembly activity was significantly diminished in the early male germ cells of Dazl-knockout mice. The DAZL-containing SGs played a protective role against heat stress-induced apoptosis by the sequestration of specific signaling molecules, such as RACK1, and the subsequent blockage of the apoptotic MAPK pathway. Based on these results, we propose that DAZL is an essential component of the SGs, which prevent male germ cells from undergoing apoptosis upon heat stress.

Extraction and functional properties of non-zein proteins in corn germ from wet-milling

USDA-ARS?s Scientific Manuscript database

This study was conducted to develop methods of extracting corn germ protein and characterize and identify potential applications of the recovered protein. Protein was extracted from both wet germ and finished (dried) germ using 0.1M NaCl as solvent. The method involved homogenization, stirring, cent...

Retrotransposons Mimic Germ Plasm Determinants to Promote Transgenerational Inheritance.

PubMed

Tiwari, Bhavana; Kurtz, Paula; Jones, Amanda E; Wylie, Annika; Amatruda, James F; Boggupalli, Devi Prasad; Gonsalvez, Graydon B; Abrams, John M

2017-10-09

Retrotransposons are a pervasive class of mobile elements present in the genomes of virtually all forms of life [1, 2]. In metazoans, these are preferentially active in the germline, which, in turn, mounts defenses that restrain their activity [3, 4]. Here we report that certain classes of retrotransposons ensure transgenerational inheritance by invading presumptive germ cells before they are formed. Using sensitized Drosophila and zebrafish models, we found that diverse classes of retrotransposons migrate to the germ plasm, a specialized region of the oocyte that prefigures germ cells and specifies the germline of descendants in the fertilized egg. In Drosophila, we found evidence for a "stowaway" model, whereby Tahre retroelements traffic to the germ plasm by mimicking oskar RNAs and engaging the Staufen-dependent active transport machinery. Consistent with this, germ plasm determinants attracted retroelement RNAs even when these components were ectopically positioned in bipolar oocytes. Likewise, vertebrate retrotransposons similarly migrated to the germ plasm in zebrafish oocytes. Together, these results suggest that germ plasm targeting represents a fitness strategy adopted by some retrotransposons to ensure transgenerational propagation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Activation of the germ-cell potential of human bone marrow-derived cells by a chemical carcinogen

PubMed Central

Liu, Chunfang; Ma, Zhan; Xu, Songtao; Hou, Jun; Hu, Yao; Yu, Yinglu; Liu, Ruilai; Chen, Zhihong; Lu, Yuan

2014-01-01

Embryonic/germ cell traits are common in malignant tumors and are thought to be involved in malignant tumor behaviors. The reasons why tumors show strong embryonic/germline traits (displaced germ cells or gametogenic programming reactivation) are controversial. Here, we show that a chemical carcinogen, 3-methyl-cholanthrene (3-MCA), can trigger the germ-cell potential of human bone marrow-derived cells (hBMDCs). 3-MCA promoted the generation of germ cell-like cells from induced hBMDCs that had undergone malignant transformation, whereas similar results were not observed in the parallel hBMDC culture at the same time point. The malignant transformed hBMDCs spontaneously and more efficiently generated into germ cell-like cells even at the single-cell level. The germ cell-like cells from induced hBMDCs were similar to natural germ cells in many aspects, including morphology, gene expression, proliferation, migration, further development, and teratocarcinoma formation. Therefore, our results demonstrate that a chemical carcinogen can reactivate the germline phenotypes of human somatic tissue-derived cells, which might provide a novel idea to tumor biology and therapy. PMID:24998261

Generation of organized germ layers from a single mouse embryonic stem cell.

PubMed

Poh, Yeh-Chuin; Chen, Junwei; Hong, Ying; Yi, Haiying; Zhang, Shuang; Chen, Junjian; Wu, Douglas C; Wang, Lili; Jia, Qiong; Singh, Rishi; Yao, Wenting; Tan, Youhua; Tajik, Arash; Tanaka, Tetsuya S; Wang, Ning

2014-05-30

Mammalian inner cell mass cells undergo lineage-specific differentiation into germ layers of endoderm, mesoderm and ectoderm during gastrulation. It has been a long-standing challenge in developmental biology to replicate these organized germ layer patterns in culture. Here we present a method of generating organized germ layers from a single mouse embryonic stem cell cultured in a soft fibrin matrix. Spatial organization of germ layers is regulated by cortical tension of the colony, matrix dimensionality and softness, and cell-cell adhesion. Remarkably, anchorage of the embryoid colony from the 3D matrix to collagen-1-coated 2D substrates of ~1 kPa results in self-organization of all three germ layers: ectoderm on the outside layer, mesoderm in the middle and endoderm at the centre of the colony, reminiscent of generalized gastrulating chordate embryos. These results suggest that mechanical forces via cell-matrix and cell-cell interactions are crucial in spatial organization of germ layers during mammalian gastrulation. This new in vitro method could be used to gain insights on the mechanisms responsible for the regulation of germ layer formation.

The making of a germ panic, then and now.

PubMed Central

Tomes, N

2000-01-01

Over the last 2 decades, a heightened interest in germs has been evident in many aspects of American popular culture, including news coverage, advertisements, and entertainment media. Although clearly a response to the AIDS epidemic and other recent disease outbreaks, current obsessions with germs have some striking parallels with a similar period of intense anxiety about disease germs that occurred between 1900 and 1940. A comparison of these 2 periods of germ "panic" suggests some of the long-term cultural trends that contributed to their making. Both germ panics reflected anxieties about societal incorporation, associated with expanding markets, transportation networks, and mass immigration. They were also shaped by new trends in public health education, journalism, advertising, and entertainment media. In comparison to the first germ panic, the current discourse about the "revenge of the superbugs" is considerably more pessimistic because of increasing worries about the environment, suspicions of governmental authority, and distrust of expert knowledge. Yet, as popular anxieties about infectious disease have increased, public health scientists have been attracting favorable coverage in their role as "medical detectives" on the trail of the "killer germ." PMID:10667179

Chromatin associated Sin3A is essential for male germ cell lineage in the mouse

PubMed Central

Pellegrino, Jessica; Castrillon, Diego H.; David, Gregory

2012-01-01

Spermatogenesis is a complex process that requires coordinated proliferation and differentiation of male germ cells. The molecular events that dictate this process are largely unknown, but are likely to involve highly regulated transcriptional control. In this study, we investigate the contribution of chromatin associated Sin3A in mouse germ cell lineage development. Genetic inactivation of Sin3A in the male germline leads to sterility that results from the early and penetrant apoptotic death observed in Sin3A-deleted germ cells, coincident with the reentry in mitosis. Sin3A-deleted testes exhibit a Sertoli-cell only phenotype, consistent with the absolute requirement for Sin3A in germ cells’ development and/or viability. Interestingly, transcripts analysis revealed that the expression program of Sertoli cells is altered upon inactivation of Sin3A in germ cells. These studies identified a central role for the mammalian Sin3-HDAC complex in the germ cell lineage, and point to an exquisite transcriptional crosstalk between germ cells and their niche to support fertility in mammals. PMID:22820070

RSPO1/β-Catenin Signaling Pathway Regulates Oogonia Differentiation and Entry into Meiosis in the Mouse Fetal Ovary

PubMed Central

Chassot, Anne-Amandine; Gregoire, Elodie P.; Lavery, Rowena; Taketo, Makoto M.; de Rooij, Dirk G.; Adams, Ian R.; Chaboissier, Marie-Christine

2011-01-01

Differentiation of germ cells into male gonocytes or female oocytes is a central event in sexual reproduction. Proliferation and differentiation of fetal germ cells depend on the sex of the embryo. In male mouse embryos, germ cell proliferation is regulated by the RNA helicase Mouse Vasa homolog gene and factors synthesized by the somatic Sertoli cells promote gonocyte differentiation. In the female, ovarian differentiation requires activation of the WNT/β-catenin signaling pathway in the somatic cells by the secreted protein RSPO1. Using mouse models, we now show that Rspo1 also activates the WNT/β-catenin signaling pathway in germ cells. In XX Rspo1−/− gonads, germ cell proliferation, expression of the early meiotic marker Stra8, and entry into meiosis are all impaired. In these gonads, impaired entry into meiosis and germ cell sex reversal occur prior to detectable Sertoli cell differentiation, suggesting that β-catenin signaling acts within the germ cells to promote oogonial differentiation and entry into meiosis. Our results demonstrate that RSPO1/β-catenin signaling is involved in meiosis in fetal germ cells and contributes to the cellular decision of germ cells to differentiate into oocyte or sperm. PMID:21991325

Cellular mechanics of germ band retraction in Drosophila.

PubMed

Lynch, Holley E; Crews, Sarah M; Rosenthal, Brett; Kim, Elliott; Gish, Robert; Echiverri, Karl; Hutson, M Shane

2013-12-15

Germ band retraction involves a dramatic rearrangement of the tissues on the surface of the Drosophila embryo. As germ band retraction commences, one tissue, the germ band, wraps around another, the amnioserosa. Through retraction the two tissues move cohesively as the highly elongated cells of the amnioserosa contract and the germ band moves so it is only on one side of the embryo. To understand the mechanical drivers of this process, we designed a series of laser ablations that suggest a mechanical role for the amnioserosa. First, we find that during mid retraction, segments in the curve of the germ band are under anisotropic tension. The largest tensions are in the direction in which the amnioserosa contracts. Second, ablating one lateral flank of the amnioserosa reduces the observed force anisotropy and leads to retraction failures. The other intact flank of amnioserosa is insufficient to drive retraction, but can support some germ band cell elongation and is thus not a full phenocopy of ush mutants. Another ablation-induced failure in retraction can phenocopy mys mutants, and does so by targeting amnioserosa cells in the same region where the mutant fails to adhere to the germ band. We conclude that the amnioserosa must play a key, but assistive, mechanical role that aids uncurling of the germ band. © 2013 Elsevier Inc. All rights reserved.

Cellular Mechanics of Germ Band Retraction in Drosophila

PubMed Central

Lynch, Holley E.; Crews, Sarah M.; Rosenthal, Brett; Kim, Elliott; Gish, Robert; Echiverri, Karl; Hutson, M. Shane

2013-01-01

Germ band retraction involves a dramatic rearrangement of the tissues on the surface of the Drosophila embryo. As germ band retraction commences, one tissue, the germ band, wraps around another, the amnioserosa. Through retraction the two tissues move cohesively as the highly elongated cells of the amnioserosa contract and the germ band moves so it is only on one side of the embryo. To understand the mechanical drivers of this process, we designed a series of laser ablations that suggest a mechanical role for the amnioserosa. First, we find that during mid retraction, segments in the curve of the germ band are under anisotropic tension. The largest tensions are in the direction in which the amnioserosa contracts. Second, ablating one lateral flank of the amnioserosa reduces the observed force anisotropy and leads to retraction failures. The other intact flank of amnioserosa is insufficient to drive retraction, but can support some germ band cell elongation and is thus not a full phenocopy of ush mutants. Another ablation-induced failure in retraction can phenocopy mys mutants, and does so by targeting amnioserosa cells in the same region where the mutant fails to adhere to the germ band. We conclude that the amnioserosa must play a key, but assistive, mechanical role that aids uncurling of the germ band. PMID:24135149

RhoA/ROCK pathway activity is essential for the correct localization of the germ plasm mRNAs in zebrafish embryos.

PubMed

Miranda-Rodríguez, Jerónimo Roberto; Salas-Vidal, Enrique; Lomelí, Hilda; Zurita, Mario; Schnabel, Denhi

2017-01-01

Zebrafish germ plasm is composed of mRNAs such as vasa and nanos and of proteins such as Bucky ball, all of which localize symmetrically in four aggregates at the distal region of the first two cleavage furrows. The coordination of actin microfilaments, microtubules and kinesin is essential for the correct localization of the germ plasm. Rho-GTPases, through their effectors, coordinate cytoskeletal dynamics. We address the participation of RhoA and its effector ROCK in germ plasm localization during the transition from two- to eight-cell embryos. We found that active RhoA is enriched along the cleavage furrow during the first two division cycles, whereas ROCK localizes at the distal region of the cleavage furrows in a similar pattern as the germ plasm mRNAs. Specific inhibition of RhoA and ROCK affected microtubules organization at the cleavage furrow; these caused the incorrect localization of the germ plasm mRNAs. The incorrect localization of the germ plasm led to a dramatic change in the number of germ cells during the blastula and 24hpf embryo stages without affecting any other developmental processes. We demonstrate that the Rho/ROCK pathway is intimately related to the determination of germ cells in zebrafish embryos. Copyright © 2016 Elsevier Inc. All rights reserved.

Human somatic cells subjected to genetic induction with six germ line-related factors display meiotic germ cell-like features

PubMed Central

Medrano, Jose V.; Martínez-Arroyo, Ana M.; Míguez, Jose M.; Moreno, Inmaculada; Martínez, Sebastián; Quiñonero, Alicia; Díaz-Gimeno, Patricia; Marqués-Marí, Ana I.; Pellicer, Antonio; Remohí, Jose; Simón, Carlos

2016-01-01

The in vitro derivation of human germ cells has attracted interest in the last years, but their direct conversion from human somatic cells has not yet been reported. Here we tested the ability of human male somatic cells to directly convert into a meiotic germ cell-like phenotype by inducing them with a combination of selected key germ cell developmental factors. We started with a pool of 12 candidates that were reduced to 6, demonstrating that ectopic expression of the germ line-related genes PRDM1, PRDM14, LIN28A, DAZL, VASA and SYCP3 induced direct conversion of somatic cells (hFSK (46, XY), and hMSC (46, XY)) into a germ cell-like phenotype in vitro. Induced germ cell-like cells showed a marked switch in their transcriptomic profile and expressed several post-meiotic germ line related markers, showed meiotic progression, evidence of epigenetic reprogramming, and approximately 1% were able to complete meiosis as demonstrated by their haploid status and the expression of several post-meiotic markers. Furthermore, xenotransplantation assays demonstrated that a subset of induced cells properly colonize the spermatogonial niche. Knowledge obtained from this work can be used to create in vitro models to study gamete-related diseases in humans. PMID:27112843

Germ tube-specific antigens of Candida albicans cell walls

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

Sundstrom, P.R.

1986-01-01

Studies were performed to characterize the surface differences between blastospores and germ tubes of the pathogenic, dimorphic yeast, Candida albicans, and to identify components of yeast cells responsible for these differences. Investigation of surfaces differences of the two growth forms was facilitated by the production of rabbit antiserum prepared against Formalin-treated yeast possessing germ tubes. To prepare antiserum specific for germ tubes, this serum was adsorbed with stationary phase blastospores. Whereas the unadsorbed antiserum reacted with both blastospore and germ tube forms by immunofluorescence and Enzyme-Linked Immunosorbent Assay, the adsorbed antiserum did not react with blastospores but detected germ tube-specificmore » antigens in hyphal forms. The differences between blastospores and germ tubes of Candida albicans, were further studied by comparing enzymatic digests of cell walls of both growth forms in radiolabeled organisms. Organisms were labeled either on the surface with /sup 125/I, or metabolically with (/sup 35/S) methionine or (/sup 3/H) mannose. Three-surface-located components (as shown by antibody adsorption and elution experiments) were precipitated from Zymolase digests. All three components were mannoproteins as shown by their ability to bind Concanavalin A, and to be labeled in protein labeling procedures, and two of these (200,000 and 155,000 molecular weight) were germ tube specific, as shown by their ability to be precipitated by germ tube-specific antiserum. Monoclonal antibodies were prepared to C. albicans, using blastospores bearing germ tubes as immunogen.« less

Black carp vasa identifies embryonic and gonadal germ cells.

PubMed

Xue, Ting; Yu, Miao; Pan, Qihua; Wang, Yizhou; Fang, Jian; Li, Lingyu; Deng, Yu; Chen, Kai; Wang, Qian; Chen, Tiansheng

2017-07-01

Identification of molecular markers is an essential step in the study of germ cells. Vasa is an RNA helicase and a well-known germ cell marker that plays a crucial role in germ cell development. Here, we identified the Vasa homolog termed Mpvasa as the first germ cell marker in black carp (Mylopharyngodon piceus). First, a 2819-bp full-length Mpvasa complementary DNA (cDNA) was cloned by PCR using degenerated primers of conserved sequences and gene-specific primers. The Mpvasa cDNA sequence encodes a 637-amino acid protein that contains eight conserved characteristic motifs of the DEAD box protein family, and shares high identity to grass carp (81%) and zebrafish (74%) vasa homologs. Second, Mpvasa expression was restricted to the gonad in adulthood by RT-PCR and Western blot analysis. The dynamic patterns of temporal-spatial expression of Mpvasa during gametogenesis were examined by in situ hybridization, and Mpvasa transcripts were strictly detected in gonadal germ cells throughout oogenesis, predominantly in immature oocytes (stage I, II, and III oocytes). Third, Mpvasa transcripts were highly detected in unfertilized eggs and early embryos, and the signal indicated a dynamic migration of the primordial germ cells during embryogenesis, suggesting that Mpvasa transcripts were maternally inherited and specifically distributed in germ cells. Taken together, these results demonstrated that Mpvasa is an applicable molecular marker for identification of gonadal and embryonic germ cells, which facilitates the isolation and utilization of germ cells in black carp.

Cytokeratin expression in mouse lacrimal gland germ epithelium.

PubMed

Hirayama, Masatoshi; Liu, Ying; Kawakita, Tetsuya; Shimmura, Shigeto; Tsubota, Kazuo

2016-05-01

The lacrimal gland secretes tear fluids that protect the ocular surface epithelium, and its dysfunction leads to dry eye disease (DED). The functional restoration of the lacrimal gland by engraftment of a bioengineered lacrimal gland using lacrimal gland germ epithelial cells has been proposed to cure DED in mice. Here, we investigate the expression profile of cytokeratins in the lacrimal gland germ epithelium to clarify their unique characteristics. We performed quantitative polymerase chain reaction (Q-PCR) and immunohistochemistry (IHC) analysis to clarify the expression profile of cytokeratin in the lacrimal gland germ epithelium. The mRNA expression of keratin (KRT) 5, KRT8, KRT14, KRT15, and KRT18 in the lacrimal gland germ epithelium was increased compared with that in mouse embryonic stem cells and the lacrimal gland germ mesenchyme, as analyzed by Q-PCR. The expression level of KRT15 increased in the transition from stem cells to lacrimal gland germ epithelium, then decreased as the lacrimal gland matured. IHC revealed that the expression set of these cytokeratins in the lacrimal gland germ epithelium was different from that in the adult lacrimal gland. The expression of KRT15 was observed in the lacrimal gland germ epithelium, and it segmentalized into some of the basal cells in the intercanulated duct in mature gland. We determined the expression profile of cytokeratins in the lacrimal gland epithelium, and identified KRT15 as a candidate unique cellular marker for the lacrimal gland germ epithelium. Copyright © 2015 Elsevier Ltd. All rights reserved.

Germ cell pluripotency, premature differentiation and susceptibility to testicular teratomas in mice

PubMed Central

Heaney, Jason D.; Anderson, Ericka L.; Michelson, Megan V.; Zechel, Jennifer L.; Conrad, Patricia A.; Page, David C.; Nadeau, Joseph H.

2012-01-01

Testicular teratomas result from anomalies in germ cell development during embryogenesis. In the 129 family of inbred strains of mice, teratomas initiate around embryonic day (E) 13.5 during the same developmental period in which female germ cells initiate meiosis and male germ cells enter mitotic arrest. Here, we report that three germ cell developmental abnormalities, namely continued proliferation, retention of pluripotency, and premature induction of differentiation, associate with teratoma susceptibility. Using mouse strains with low versus high teratoma incidence (129 versus 129-Chr19MOLF/Ei), and resistant to teratoma formation (FVB), we found that germ cell proliferation and expression of the pluripotency factor Nanog at a specific time point, E15.5, were directly related with increased tumor risk. Additionally, we discovered that genes expressed in pre-meiotic embryonic female and adult male germ cells, including cyclin D1 (Ccnd1) and stimulated by retinoic acid 8 (Stra8), were prematurely expressed in teratoma-susceptible germ cells and, in rare instances, induced entry into meiosis. As with Nanog, expression of differentiation-associated factors at a specific time point, E15.5, increased with tumor risk. Furthermore, Nanog and Ccnd1, genes with known roles in testicular cancer risk and tumorigenesis, respectively, were co-expressed in teratoma-susceptible germ cells and tumor stem cells, suggesting that retention of pluripotency and premature germ cell differentiation both contribute to tumorigenesis. Importantly, Stra8-deficient mice had an 88% decrease in teratoma incidence, providing direct evidence that premature initiation of the meiotic program contributes to tumorigenesis. These results show that deregulation of the mitotic-meiotic switch in XY germ cells contributes to teratoma initiation. PMID:22438569

Germ-line mutations of the p53 tumor suppressor gene in patients with high risk for cancer inactivate the p53 protein.

PubMed Central

Frebourg, T; Kassel, J; Lam, K T; Gryka, M A; Barbier, N; Andersen, T I; Børresen, A L; Friend, S H

1992-01-01

Germ-line mutations in the p53 tumor suppressor gene have been observed in patients with Li-Fraumeni syndrome, brain tumors, second malignancies, and breast cancers. It is unclear whether all of these mutations have inactivated p53 and thereby provide an increased risk for cancer. Therefore, it is necessary to establish the biological significance of these germ-line mutations by the functional and structural analysis of the resulting mutant p53 proteins. We analyzed the ability of seven germ-line mutant proteins observed in patients with Li-Fraumeni syndrome, second primary neoplasms, or familial breast cancer to block the growth of malignant cells and compared the structural properties of the mutant proteins to that of the wild-type protein. Six of seven missense mutations disrupted the growth inhibitory properties and structure of the wild-type protein. One germ-line mutation retained the features of the wild-type p53. Genetic analysis of the breast cancer family in which this mutation was observed indicated that this germ-line mutation was not associated with the development of cancer. These results demonstrate that germ-line p53 mutations observed in patients with Li-Fraumeni syndrome and with second malignancies have inactivated the p53 tumor suppressor gene. The inability of the germ-line p53 mutants to block the growth of malignant cells can explain why patients with these germ-line mutations have an increased risk for cancer. The observation of a functionally silent germ-line mutation indicates that, before associating a germ-line tumor suppressor gene mutation with cancer risk, it is prudent to consider its functional significance. Images PMID:1631137

Germ-line mutations of the p53 tumor suppressor gene in patients with high risk for cancer inactivate the p53 protein.

PubMed

Frebourg, T; Kassel, J; Lam, K T; Gryka, M A; Barbier, N; Andersen, T I; Børresen, A L; Friend, S H

1992-07-15

Germ-line mutations in the p53 tumor suppressor gene have been observed in patients with Li-Fraumeni syndrome, brain tumors, second malignancies, and breast cancers. It is unclear whether all of these mutations have inactivated p53 and thereby provide an increased risk for cancer. Therefore, it is necessary to establish the biological significance of these germ-line mutations by the functional and structural analysis of the resulting mutant p53 proteins. We analyzed the ability of seven germ-line mutant proteins observed in patients with Li-Fraumeni syndrome, second primary neoplasms, or familial breast cancer to block the growth of malignant cells and compared the structural properties of the mutant proteins to that of the wild-type protein. Six of seven missense mutations disrupted the growth inhibitory properties and structure of the wild-type protein. One germ-line mutation retained the features of the wild-type p53. Genetic analysis of the breast cancer family in which this mutation was observed indicated that this germ-line mutation was not associated with the development of cancer. These results demonstrate that germ-line p53 mutations observed in patients with Li-Fraumeni syndrome and with second malignancies have inactivated the p53 tumor suppressor gene. The inability of the germ-line p53 mutants to block the growth of malignant cells can explain why patients with these germ-line mutations have an increased risk for cancer. The observation of a functionally silent germ-line mutation indicates that, before associating a germ-line tumor suppressor gene mutation with cancer risk, it is prudent to consider its functional significance.

Origin and development of the germ line in sea stars

PubMed Central

Wessel, Gary M.; Fresques, Tara; Kiyomoto, Masato; Yajima, Mamiko; Zazueta, Vanesa

2014-01-01

This review summarizes and integrates our current understanding of how sea stars make gametes. Although little is known of the mechanism of germ line formation in these animals, recent results point to specific cells and to cohorts of molecules in the embryos and larvae that may lay the ground work for future research efforts. A coelomic outpocketing forms in the posterior of the gut in larvae, referred to as the posterior enterocoel (PE), that when removed, significantly reduces the number of germ cell later in larval growth. This same PE structure also selectively accumulates several germ-line associated factors – vasa, nanos, piwi – and excludes factors involved in somatic cell fate. Since its formation is relatively late in development, these germ cells may form by inductive mechanisms. When integrated into the morphological observations of germ cells and gonad development in larvae, juveniles, and adults, the field of germ line determination appears to have a good model system to study inductive germ line determination to complement the recent work on the molecular mechanisms in mice. We hope this review will also guide investigators interested in germ line determination and regulation of the germ line in how these animals can help in this research field. The review is not intended to be comprehensive – sea star reproduction has been studied over 100 years and many reviews are comprehensive in their coverage of, for example, seasonal growth of the gonads in response to light, nutrient, and temperature. Rather the intent of this review is to help the reader focus on new experimental results attached to the historical underpinnings of how the germ cell functions in sea stars with particular emphasis to clarify the important areas of priority for future research. PMID:24648114

Autophagy and Apoptosis Act as Partners to Induce Germ Cell Death after Heat Stress in Mice

PubMed Central

Zhang, Mianqiu; Jiang, Min; Bi, Ye; Zhu, Hui; Zhou, Zuomin; Sha, Jiahao

2012-01-01

Testicular heating suppresses spermatogenesis which is marked by germ cell loss via apoptotic pathways. Recently, it is reported that autophagy also can be induced by heat treatment in somatic cells. In this study, the status of autophagy in germ cells after heat treatment, as well as the partnership between autophagy and apoptosis in these cells was investigated. The results demonstrated that besides initiating apoptotic pathways, heat also induced autophagic pathways in germ cells. Exposure of germ cells to hyperthermia resulted in several specific features of the autophagic process, including autophagosome formation and the conversion of LC3-I to LC3-II. Furthermore, the ubiquitin-like protein conjugation system was implicated as being likely responsible for heat-induced autophagy in germ cells since all genes involving this system were found to be expressed in the testes. In addition, the upstream protein in this system, Atg7 (Autophagy-related gene 7), was found to be expressed in all types of spermatogenic cells, and its expression level was positively correlated with the level of autophagy in germ cells. As a result, Atg7 was selected as the investigative target to further analyze the role of autophagy in heat-induced germ cell death. It was shown that down expression of Atg7 protein resulted in the notable decrease in the level of autophagy in heat-treated germ cells, and this down-regulation of autophagy caused by Atg7 knockdown further reduced the apoptotic rate of germ cells. These results suggest that autophagy plays a positive role in the process of germ cell apoptosis after heat treatment. In conclusion, this study demonstrates that heat triggers autophagy and apoptosis in germ cells. These two mechanisms might act as partners, not antagonist, to induce cell death and lead to eventual destruction of spermatogenesis. PMID:22848486

Identification of genes expressed in the hermaphrodite germ line of C. elegans using SAGE

PubMed Central

Wang, Xin; Zhao, Yongjun; Wong, Kim; Ehlers, Peter; Kohara, Yuji; Jones, Steven J; Marra, Marco A; Holt, Robert A; Moerman, Donald G; Hansen, Dave

2009-01-01

Background Germ cells must progress through elaborate developmental stages from an undifferentiated germ cell to a fully differentiated gamete. Some of these stages include exiting mitosis and entering meiosis, progressing through the various stages of meiotic prophase, adopting either a male (sperm) or female (oocyte) fate, and completing meiosis. Additionally, many of the factors needed to drive embryogenesis are synthesized in the germ line. To increase our understanding of the genes that might be necessary for the formation and function of the germ line, we have constructed a SAGE library from hand dissected C. elegans hermaphrodite gonads. Results We found that 4699 genes, roughly 21% of all known C. elegans genes, are expressed in the adult hermaphrodite germ line. Ribosomal genes are highly expressed in the germ line; roughly four fold above their expression levels in the soma. We further found that 1063 of the germline-expressed genes have enriched expression in the germ line as compared to the soma. A comparison of these 1063 germline-enriched genes with a similar list of genes prepared using microarrays revealed an overlap of 460 genes, mutually reinforcing the two lists. Additionally, we identified 603 germline-enriched genes, supported by in situ expression data, which were not previously identified. We also found >4 fold enrichment for RNA binding proteins in the germ line as compared to the soma. Conclusion Using multiple technological platforms provides a more complete picture of global gene expression patterns. Genes involved in RNA metabolism are expressed at a significantly higher level in the germ line than the soma, suggesting a stronger reliance on RNA metabolism for control of the expression of genes in the germ line. Additionally, the number and expression level of germ line expressed genes on the X chromosome is lower than expected based on a random distribution. PMID:19426519

Establishment of intraperitoneal germ cell transplantation for critically endangered Chinese sturgeon Acipenser sinensis.

PubMed

Ye, Huan; Li, Chuang-Ju; Yue, Hua-Mei; Du, Hao; Yang, Xiao-Ge; Yoshino, Tasuku; Hayashida, Takao; Takeuchi, Yutaka; Wei, Qi-Wei

2017-05-01

Recent progress in germ cell transplantation techniques in fish has paved the way for the conservation of endangered species. Here, we developed an intraperitoneal germ cell transplantation procedure using Chinese and Dabry's sturgeon as donor and recipient species, respectively. Histological analysis revealed that primordial germ cells migrated on the peritoneal wall at 16 days post-hatch (dph) in Dabry's sturgeon. The genital ridges of Dabry's sturgeon (recipient) first formed at 28 dph, suggesting that for successful colonization of donor germ cells in the recipient gonads, the transplantation should be performed earlier than this age. Sexual dimorphism of gonadal structure was first observed at 78 dph. Gonadal germ cell proliferation was not seen in either sex during this period. Immunohistochemistry using the anti-Vasa antibody found that donor testes from 2-year-old Dabry's sturgeon mainly consisted of single- or paired-type A spermatogonia, while donor ovaries from 11.5-year-old Chinese sturgeon had perinucleolus stage oocytes and clusters of oogonia. Donor cells isolated from Dabry's sturgeon testes or Chinese sturgeon ovary labeled with PKH26 fluorescent dye were transplanted into the peritoneal cavity of the 7- or 8-dph Dabry's sturgeon larvae. More than 90% and 70% of transplanted larvae survived after 2 days post-transplantation (dpt) and 51 dpt, respectively. At 51 dpt, PKH26-labeled cells exhibiting germ cell-specific nuclear morphology and diameter were observed in excised recipient gonads by fluorescent and confocal microscopy. The colonization rate of allogeneic testicular germ cell transplantation (Group 1) was 70%, while that of two batches of xenogeneic ovarian germ cell transplantation (Group 2 and Group 3) were 6.7% and 40%, respectively. The ratio of colonized germ cells to endogenous germ cells was 11.96%, 5.35% and 3.56% for Group 1, Group 2 and Group 3, respectively. Thus, we established a germ cell transplantation technique for the critically endangered Chinese sturgeon using the most closely related species as a recipient and demonstrated the successful preparation of transplantable female germ cells from aged adult Chinese sturgeon. Copyright © 2017 Elsevier Inc. All rights reserved.

Diagnostic markers for germ cell neoplasms: from placental-like alkaline phosphatase to micro-RNAs.

PubMed

Rajpert-De Meyts, Ewa; Nielsen, John E; Skakkebaek, Niels E; Almstrup, Kristian

2015-01-01

This concise review summarises tissue and serum markers useful for differential diagnosis of germ cell tumours (GCT), with focus on the most common testicular GCT (TGCT). GCT are characterised by phenotypic heterogeneity due to largely retained embryonic pluripotency and aberrant somatic differentiation. TGCT that occur in young men are divided into two main types, seminoma and nonseminoma, both derived from a pre-invasive germ cell neoplasia in situ (GCNIS), which originates from transformed foetal gonocytes. In severely dysgenetic gonads, a GCNIS-resembling lesion is called gonadoblastoma. GCT occur rarely in young children (infantile GCT) in whom the pathogenesis is different (no GCNIS/gonadoblastoma stage) but the histopathological features are similar to the adult GCT. The rare spermatocytic tumour of older men is derived from post-pubertal spermatogonia that clonally expand due to gain-of function mutations in survival-promoting genes (e.g. FGFR3, HRAS), thus this tumour has a different expression profile than GCNIS-derived TGCT. Clinically most informative immunohistochemical markers for GCT, except teratoma, are genes expressed in primordial germ cells/gonocytes and embryonic pluripotency-related factors, such as placental-like alkaline phosphatase (PLAP), OCT4 (POU5F1), NANOG, AP-2γ (TFAP2C) and LIN28, which are not expressed in normal adult germ cells. Some of these markers can also be used for immunocytochemistry to detect GCNIS or incipient tumours in semen samples. Gene expression in GCT is regulated in part by DNA and histone modifications, and the epigenetic profile of these tumours is characterised by genome-wide demethylation, except nonseminomas. In addition, a recently discovered mechanism of post-genomic gene expression regulation involves small non-coding RNAs, predominantly micro-RNA (miR). Testicular GCT display micro-RNA profiles similar to embryonic stem cells. Targeted miRNA-based blood tests for miR-371-3 and miR-367 clusters are currently under development and hold a great promise for the future. In some patients miR-based tests may be even more sensitive than the classical serum tumour markers, β -chorio-gonadotrophin (β-hCG), α-fetoprotein (AFP) and lactate dehydrogenase (LDH), which are currently used in the clinic. In summary, research advances have provided clinicians with a panel of molecular markers, which allow specific diagnosis of various subtypes of GCT and are very useful for early detection at the precursor stage and for monitoring of patients during the follow-up.

MEETING REPORT ASSESSING HUMAN GERM-CELL MUTAGENESIS IN THE POST-GENOME ERA: A CELEBRATION OF THE LEGACY OF WILLIAM LAWSON (BILL) RUSSELL

EPA Science Inventory

Although numerous germ-cell mutagens have been identified in animal model systems, to date, no human germ-cell mutagens have been confirmed. Because the genomic integrity of our germ cells is essential for the continuation of the human species, a resolution of this enduring conu...

Molecular biological features of male germ cell differentiation

PubMed Central

HIROSE, MIKA; TOKUHIRO, KEIZO; TAINAKA, HITOSHI; MIYAGAWA, YASUSHI; TSUJIMURA, AKIRA; OKUYAMA, AKIHIKO; NISHIMUNE, YOSHITAKE

2007-01-01

Somatic cell differentiation is required throughout the life of a multicellular organism to maintain homeostasis. In contrast, germ cells have only one specific function; to preserve the species by conveying the parental genes to the next generation. Recent studies of the development and molecular biology of the male germ cell have identified many genes, or isoforms, that are specifically expressed in the male germ cell. In the present review, we consider the unique features of male germ cell differentiation. (Reprod Med Biol 2007; 6: 1–9) PMID:29699260

A new glycosylated dihydrophaseic acid from cacao germs (Theobroma cacao L.).

PubMed

Sannohe, Yumiko; Gomi, Shuichi; Murata, Takashi; Ohyama, Makoto; Yonekura, Kumiko; Kanegae, Minoru; Koga, Jinichiro

2011-01-01

Cacao beans are composed of cacao nibs and germs. Although numerous chemical and physiological studies on cacao nib compounds have been reported, there is little information on cacao germ compounds. We therefore analyzed an extract from the cacao germ, and found two compounds that were specific to the germ. One of these two compounds was identified as the new glycosylated abscisic acid metabolite, dihydrophaseic acid-4'-O-6″-(β-ribofuranosyl)-β-glucopyranoside, and the other as the known compound, dihydrophaseic acid-4'-O-β-D-glucopyranoside.

Identifying functional cancer-specific miRNA-mRNA interactions in testicular germ cell tumor.

PubMed

Sedaghat, Nafiseh; Fathy, Mahmood; Modarressi, Mohammad Hossein; Shojaie, Ali

2016-09-07

Testicular cancer is the most common cancer in men aged between 15 and 35 and more than 90% of testicular neoplasms are originated at germ cells. Recent research has shown the impact of microRNAs (miRNAs) in different types of cancer, including testicular germ cell tumor (TGCT). MicroRNAs are small non-coding RNAs which affect the development and progression of cancer cells by binding to mRNAs and regulating their expressions. The identification of functional miRNA-mRNA interactions in cancers, i.e. those that alter the expression of genes in cancer cells, can help delineate post-regulatory mechanisms and may lead to new treatments to control the progression of cancer. A number of sequence-based methods have been developed to predict miRNA-mRNA interactions based on the complementarity of sequences. While necessary, sequence complementarity is, however, not sufficient for presence of functional interactions. Alternative methods have thus been developed to refine the sequence-based interactions using concurrent expression profiles of miRNAs and mRNAs. This study aims to find functional cancer-specific miRNA-mRNA interactions in TGCT. To this end, the sequence-based predicted interactions are first refined using an ensemble learning method, based on two well-known methods of learning miRNA-mRNA interactions, namely, TaLasso and GenMiR++. Additional functional analyses were then used to identify a subset of interactions to be most likely functional and specific to TGCT. The final list of 13 miRNA-mRNA interactions can be potential targets for identifying TGCT-specific interactions and future laboratory experiments to develop new therapies. Copyright © 2016 Elsevier Ltd. All rights reserved.

Heavy Ion Testing at the Galactic Cosmic Ray Energy Peak

NASA Technical Reports Server (NTRS)

Pellish, Jonathan A.; Xapsos, M. A.; LaBel, K. A.; Marshall, P. W.; Heidel, D. F.; Rodbell, K. P.; Hakey, M. C.; Dodd, P. E.; Shaneyfelt, M. R.; Schwank, J. R.;

Bypass Flow Resistance in Prismatic Gas-Cooled Nuclear Reactors

DOE PAGES

McEligot, Donald M.; Johnson, Richard W.

2016-12-20

Available computational fluid dynamics (CFD) predictions of pressure distributions in the vertical bypass flow between blocks in a prismatic gas-cooled reactor (GCR) have been analyzed to deduce apparent friction factors and loss coefficients for systems and network codes. We performed calculations for vertical gap spacings "s" of 2, 6 and 10 mm, horizontal gaps between the blocks of two mm and two flow rates, giving a range of gap Reynolds numbers Re Dh of about 40 to 5300. Laminar predictions of the fully-developed friction factor f fd were about three to ten per cent lower than the classical infinitely-wide channelmore » In the entry region, the local apparent friction factor was slightly higher than the classic idealized case but the hydraulic entry length L hy was approximately the same. The per cent reduction in flow resistance was greater than the per cent increase in flow area at the vertical corners of the blocks. The standard k-ϵ model was employed for flows expected to be turbulent. Its predictions of f fd and flow resistance were significantly higher than direct numerical simulations for the classic case; the value of L hy was about thirty gap spacings. Initial quantitative information for entry coefficients and loss coefficients for the expansion-contraction junctions between blocks is also presented. Our study demonstrates how CFD predictions can be employed to provide integral quantities needed in systems and network codes.« less

Bypass Flow Resistance in Prismatic Gas-Cooled Nuclear Reactors

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

McEligot, Donald M.; Johnson, Richard W.

Available computational fluid dynamics (CFD) predictions of pressure distributions in the vertical bypass flow between blocks in a prismatic gas-cooled reactor (GCR) have been analyzed to deduce apparent friction factors and loss coefficients for systems and network codes. We performed calculations for vertical gap spacings "s" of 2, 6 and 10 mm, horizontal gaps between the blocks of two mm and two flow rates, giving a range of gap Reynolds numbers Re Dh of about 40 to 5300. Laminar predictions of the fully-developed friction factor f fd were about three to ten per cent lower than the classical infinitely-wide channelmore » In the entry region, the local apparent friction factor was slightly higher than the classic idealized case but the hydraulic entry length L hy was approximately the same. The per cent reduction in flow resistance was greater than the per cent increase in flow area at the vertical corners of the blocks. The standard k-ϵ model was employed for flows expected to be turbulent. Its predictions of f fd and flow resistance were significantly higher than direct numerical simulations for the classic case; the value of L hy was about thirty gap spacings. Initial quantitative information for entry coefficients and loss coefficients for the expansion-contraction junctions between blocks is also presented. Our study demonstrates how CFD predictions can be employed to provide integral quantities needed in systems and network codes.« less

Surfing the wave, cycle, life history, and genes/proteins expressed by testicular germ cells. Part 5: intercellular junctions and contacts between germs cells and Sertoli cells and their regulatory interactions, testicular cholesterol, and genes/proteins associated with more than one germ cell generation.

PubMed

Hermo, Louis; Pelletier, R-Marc; Cyr, Daniel G; Smith, Charles E

2010-04-01

In the testis, cell adhesion and junctional molecules permit specific interactions and intracellular communication between germ and Sertoli cells and apposed Sertoli cells. Among the many adhesion family of proteins, NCAM, nectin and nectin-like, catenins, and cadherens will be discussed, along with gap junctions between germ and Sertoli cells and the many members of the connexin family. The blood-testis barrier separates the haploid spermatids from blood borne elements. In the barrier, the intercellular junctions consist of many proteins such as occludin, tricellulin, and claudins. Changes in the expression of cell adhesion molecules are also an essential part of the mechanism that allows germ cells to move from the basal compartment of the seminiferous tubule to the adluminal compartment thus crossing the blood-testis barrier and well-defined proteins have been shown to assist in this process. Several structural components show interactions between germ cells to Sertoli cells such as the ectoplasmic specialization which are more closely related to Sertoli cells and tubulobulbar complexes that are processes of elongating spermatids embedded into Sertoli cells. Germ cells also modify several Sertoli functions and this also appears to be the case for residual bodies. Cholesterol plays a significant role during spermatogenesis and is essential for germ cell development. Lastly, we list genes/proteins that are expressed not only in any one specific generation of germ cells but across more than one generation. Copyright 2009 Wiley-Liss, Inc.

Male Rat Germ Cells Display Age-Dependent and Cell-Specific Susceptibility in Response to Oxidative Stress Challenges1

PubMed Central

Selvaratnam, Johanna; Paul, Catriona; Robaire, Bernard

2015-01-01

For decades male germ cells were considered unaffected by aging, due to the fact that males continue to generate sperm into old age; however, evidence indicates that germ cells from aged males are of lower quality than those of young males. The current study examines the effects of aging on pachytene spermatocytes and round spermatids, and is the first study to culture these cells in isolation for an extended period. Our objective is to determine the cell-specific responses germ cells have to aging and oxidative insult. Culturing isolated germ cells from young and aged Brown Norway rats revealed that germ cells from aged males displayed an earlier decline in viability, elevated levels of reactive oxygen species (ROS), and increased spermatocyte DNA damage, compared to young males. Furthermore, oxidative insult by prooxidant 3-morpholinosydnonimine provides insight into how spermatocytes and spermatids manage excess ROS. Genome-wide microarray analyses revealed that several transcripts for antioxidants, Sod1, Cat, and Prdxs, were up-regulated in response to ROS in germ cells from young males while being expressed at lower levels in the aged. In contrast, the expression of DNA damage repair genes Rad50 and Atm were increased in the germ cells from aged animals. Our data indicate that as germ cells undergo spermatogenesis, they adapt and respond to oxidative stress differently, depending on their phase of development, and the process of aging results in redox dysfunction. Thus, even at early stages of spermatogenesis, germ cells from aged males are unable to mount an appropriate response to manage oxidative stress. PMID:26224006

Light and electron microscopic analyses of Vasa expression in adult germ cells of the fish medaka.

PubMed

Yuan, Yongming; Li, Mingyou; Hong, Yunhan

2014-07-15

Germ cells of diverse animal species have a unique membrane-less organelle called germ plasm (GP). GP is usually associated with mitochondria and contains RNA binding proteins and mRNAs of germ genes such as vasa. GP has been described as the mitochondrial cloud (MC), intermitochondrial cement (IC) and chromatoid body (CB). The mechanism underlying varying GP structures has remained incompletely understood. Here we report the analysis of GP through light and electron microscopy by using Vasa as a marker in adult male germ cells of the fish medaka (Oryzias latipes). Immunofluorescence light microscopy revealed germ cell-specific Vasa expression. Vasa is the most abundant in mitotic germ cells (oogonia and spermatogonia) and reduced in meiotic germ cells. Vasa in round spermatids exist as a spherical structure reminiscent of CB. Nanogold immunoelectron microscopy revealed subcellular Vasa redistribution in male germ cells. Vasa in spermatogonia concentrates in small areas of the cytoplasm and is surrounded by mitochondria, which is reminiscent of MC. Vasa is intermixed with mitochondria to form IC in primary spermatocytes, appears as the free cement (FC) via separation from mitochondria in secondary spermatocyte and becomes condensed in CB at the caudal pole of round spermatids. During spermatid morphogenesis, Vasa redistributes and forms a second CB that is a ring-like structure surrounding the dense fiber of the flagellum in the midpiece. These structures resemble those described for GP in various species. Thus, Vasa identifies GP and adopts varying structures via dynamic reorganization at different stages of germ cell development. Copyright © 2014 Elsevier B.V. All rights reserved.

Stochastic Seeding Coupled with mRNA Self-Recruitment Generates Heterogeneous Drosophila Germ Granules.

PubMed

Niepielko, Matthew G; Eagle, Whitby V I; Gavis, Elizabeth R

2018-06-18

The formation of ribonucleoprotein assemblies called germ granules is a conserved feature of germline development. In Drosophila, germ granules form at the posterior of the oocyte in a specialized cytoplasm called the germ plasm, which specifies germline fate during embryogenesis. mRNAs, including nanos (nos) and polar granule component (pgc), that function in germline development are localized to the germ plasm through their incorporation into germ granules, which deliver them to the primordial germ cells. Germ granules are nucleated by Oskar (Osk) protein and contain varying combinations and quantities of their constituent mRNAs, which are organized as spatially distinct, multi-copy homotypic clusters. The process that gives rise to such heterogeneous yet organized granules remains unknown. Here, we show that individual nos and pgc transcripts can populate the same nascent granule, and these first transcripts then act as seeds, recruiting additional like transcripts to form homotypic clusters. Within a granule, homotypic clusters grow independently of each other but depend on the simultaneous acquisition of additional Osk. Although granules can contain multiple clusters of a particular mRNA, granule mRNA content is dominated by cluster size. These results suggest that the accumulation of mRNAs in the germ plasm is controlled by the mRNAs themselves through their ability to form homotypic clusters; thus, RNA self-association drives germ granule mRNA localization. We propose that a stochastic seeding and self-recruitment mechanism enables granules to simultaneously incorporate many different mRNAs while ensuring that each becomes enriched to a functional threshold. Copyright © 2018 Elsevier Ltd. All rights reserved.

Germ cell transplantation in an azoospermic Klinefelter bull.

PubMed

Joerg, Hannes; Janett, Fredi; Schlatt, Stefan; Mueller, Simone; Graphodatskaya, Daria; Suwattana, Duangsmorn; Asai, Mika; Stranzinger, Gerald

2003-12-01

Germ cell transplantation is a technique that transfers donor testicular cells into recipient testes. A population of germ cells can colonize the recipient testis, initiate spermatogenesis, and produce sperm capable of fertilization. In the present study, a nonmosaic Klinefelter bull was used as a germ cell recipient. The donor cell suspension was introduced into the rete testis using ultrasound-guided puncture. A pulsatile administration of GnRH was performed to stimulate spermatogenesis. The molecular approach to detect donor cells was done by a quantitative polymerase chain reaction with allele discrimination based on a genetic mutation between donor and recipient. Therefore, a known genetic mutation, associated with coat-color phenotype, was used to calculate the ratio of donor to recipient cells in the biopsy specimens and ejaculates for 10 mo. After slaughtering, meiotic preparations were performed. The injected germ cells did not undergo spermatogenesis. Six months after germ cell transplantation, the donor cells were rejected, which indicates that the donor cells could not incorporate in the testis. The hormone stimulation showed that the testosterone-producing Leydig cells were functionally intact. Despite subfertility therapy, neither the recipient nor the donor cells underwent spermatogenesis. Therefore, nonmosaic Klinefelter bulls are not suitable as germ cell recipients. Future germ cell recipients in cattle could be mosaic Klinefelters, interspecies hybrids, bulls with Sertoli cell-only syndrome, or bulls with disrupted germ cell migration caused by RNA interference.

Cross-talk between miR-471-5p and autophagy component proteins regulates LC3-associated phagocytosis (LAP) of apoptotic germ cells.

PubMed

Panneerdoss, Subbarayalu; Viswanadhapalli, Suryavathi; Abdelfattah, Nourhan; Onyeagucha, Benjamin C; Timilsina, Santosh; Mohammad, Tabrez A; Chen, Yidong; Drake, Michael; Vuori, Kristiina; Kumar, T Rajendra; Rao, Manjeet K

2017-09-19

Phagocytic clearance of apoptotic germ cells by Sertoli cells is vital for germ cell development and differentiation. Here, using a tissue-specific miRNA transgenic mouse model, we show that interaction between miR-471-5p and autophagy member proteins regulates clearance of apoptotic germ cells via LC3-associated phagocytosis (LAP). Transgenic mice expressing miR-471-5p in Sertoli cells show increased germ cell apoptosis and compromised male fertility. Those effects are due to defective engulfment and impaired LAP-mediated clearance of apoptotic germ cells as miR-471-5p transgenic mice show lower levels of Dock180, LC3, Atg12, Becn1, Rab5 and Rubicon in Sertoli cells. Our results reveal that Dock180 interacts with autophagy member proteins to constitute a functional LC3-dependent phagocytic complex. We find that androgen regulates Sertoli cell phagocytosis by controlling expression of miR-471-5p and its target proteins. These findings suggest that recruitment of autophagy machinery is essential for efficient clearance of apoptotic germ cells by Sertoli cells using LAP.Although phagocytic clearance of apoptotic germ cells by Sertoli cells is essential for spermatogenesis, little of the mechanism is known. Here the authors show that Sertoli cells employ LC3-associated phagocytosis (LAP) by recruiting autophagy member proteins to clear apoptotic germ cells.

Unclassified mixed germ cell-sex cord-stromal tumor with multiple malignant cellular elements in a young woman: a case report and review of the literature.

PubMed

Pang, Shujie; Zhang, Lin; Shi, Yiquan; Liu, Yixin

2014-01-01

Unclassified mixed germ cell-sex cord-stromal tumor composed of germ cells and sex cord derivatives is a rare neoplasm. Approximately 10% of such tumors have malignant germ cell components. We report the case of a 28 year-old female with a right adnexal mass measuring 8 cm in greatest dimension, containing areas with both germ cell and sex cord components. The germ cell portion contained multiple growth patterns with a malignant appearance, while the sex cord element consisted mainly of annular tubules. Within the malignant germ cell elements was a dysgerminoma that accounted for approximately 75% of the tumor volume. Other malignant germ cell elements included yolk sac tumor, embryonal carcinoma, and choriocarcinoma, which comprised about 15% of the tumor volume. The annular tubule structures comprised about 10% of the total tumor volume. To our knowledge, this is the first case reported in the literature of an unclassified mixed germ cell-sex cord-stromal tumor associated with embryonal carcinoma components. The patient had a 46XX karyotype, regular menstrual periods, and no evidence of gross abnormalities in the contralateral ovary. The patient remained clinically well and disease-free 2 years after surgery. In addition to a thorough case description, the literature concerning this entity is reviewed and discussed.

The planarian nanos-like gene Smednos is expressed in germline and eye precursor cells during development and regeneration.

PubMed

Handberg-Thorsager, Mette; Saló, Emili

2007-05-01

Planarians are highly regenerative organisms with the ability to remake all their cell types, including the germ cells. The germ cells have been suggested to arise from totipotent neoblasts through epigenetic mechanisms. Nanos is a zinc-finger protein with a widely conserved role in the maintenance of germ cell identity. In this work, we describe the expression of a planarian nanos-like gene Smednos in two kinds of precursor cells namely, primordial germ cells and eye precursor cells, during both development and regeneration of the planarian Schmidtea mediterranea. In sexual planarians, Smednos is expressed in presumptive male primordial germ cells of embryos from stage 8 of embryogenesis and throughout development of the male gonads and in the female primordial germ cells of the ovary. Thus, upon hatching, juvenile planarians do possess primordial germ cells. In the asexual strain, Smednos is expressed in presumptive male and female primordial germ cells. During regeneration, Smednos expression is maintained in the primordial germ cells, and new clusters of Smednos-positive cells appear in the regenerated tissue. Remarkably, during the final stages of development (stage 8 of embryogenesis) and during regeneration of the planarian eye, Smednos is expressed in cells surrounding the differentiating eye cells, possibly corresponding to eye precursor cells. Our results suggest that similar genetic mechanisms might be used to control the differentiation of precursor cells during development and regeneration in planarians.

Childhood Central Nervous System Germ Cell Tumors Treatment (PDQ®)—Patient Version

Cancer.gov

Childhood central nervous system (CNS) germ cell tumors form from germ cells (a type of cell that forms as a fetus develops and later becomes sperm in the testicles or eggs in the ovaries). Learn about the signs, tests to diagnose, and treatment of pediatric germ cell tumors in the brain in this expert-reviewed summary.

Mechano-logical model of C. elegans germ line suggests feedback on the cell cycle

PubMed Central

Atwell, Kathryn; Qin, Zhao; Gavaghan, David; Kugler, Hillel; Hubbard, E. Jane Albert; Osborne, James M.

2015-01-01

The Caenorhabditis elegans germ line is an outstanding model system in which to study the control of cell division and differentiation. Although many of the molecules that regulate germ cell proliferation and fate decisions have been identified, how these signals interact with cellular dynamics and physical forces within the gonad remains poorly understood. We therefore developed a dynamic, 3D in silico model of the C. elegans germ line, incorporating both the mechanical interactions between cells and the decision-making processes within cells. Our model successfully reproduces key features of the germ line during development and adulthood, including a reasonable ovulation rate, correct sperm count, and appropriate organization of the germ line into stably maintained zones. The model highlights a previously overlooked way in which germ cell pressure may influence gonadogenesis, and also predicts that adult germ cells might be subject to mechanical feedback on the cell cycle akin to contact inhibition. We provide experimental data consistent with the latter hypothesis. Finally, we present cell trajectories and ancestry recorded over the course of a simulation. The novel approaches and software described here link mechanics and cellular decision-making, and are applicable to modeling other developmental and stem cell systems. PMID:26428008

Lin28a regulates germ cell pool size and fertility

PubMed Central

Shinoda, Gen; de Soysa, T. Yvanka; Seligson, Marc T.; Yabuuchi, Akiko; Fujiwara, Yuko; Huang, Pei Yi; Hagan, John P.; Gregory, Richard I.; Moss, Eric G.; Daley, George Q.

2013-01-01

Overexpression of LIN28A is associated with human germ cell tumors and promotes primordial germ cell (PGC) development from embryonic stem cells in vitro and in chimeric mice. Knockdown of Lin28a inhibits PGC development in vitro, but how constitutional Lin28a deficiency affects the mammalian reproductive system in vivo remains unknown. Here, we generated Lin28a knockout (KO) mice and found that Lin28a deficiency compromises the size of the germ cell pool in both males and females by affecting PGC proliferation during embryogenesis. Interestingly however, in Lin28a KO males the germ cell pool partially recovers during postnatal expansion, while fertility remains impaired in both males and females mated to wild type mice. Embryonic overexpression of let-7, a microRNA negatively regulated by Lin28a, reduces the germ cell pool, corroborating the role of the Lin28a/let-7 axis in regulating the germ lineage. PMID:23378032

Recent and planned developments in the CARI program.

DOT National Transportation Integrated Search

2013-04-01

CARI-6 is the sixth major release of galactic cosmic radiation (GCR) dose calculation software developed by the U.S. Federal Aviation Administration (FAA). The software is of benefit to the FAA and the public as a tool used by scientists investigatin...

Interaction of Space Radiation with Agriculture on the Moon

NASA Astrophysics Data System (ADS)

Guven, U. G.; Goel, E. G.

2017-10-01

This paper proposes to understand the effects of GCR and SEP on the plants and agriculture, which is the primary step to colonization at any celestial site. This paper is dedicated to achieve this understanding to aid plantation missions on the Moon.

Isolation and purification of wheat germ agglutinin and analysis of its properties

NASA Astrophysics Data System (ADS)

Wang, Han

2017-12-01

In this paper, the wheat germ agglutinin was isolated and purified by affinity chromatography of chicken ovomucoid as ligand. The physicochemical properties were analyzed. The chicken ovomucoid was isolated from egg white and conjugated to affinity chromatography column agarose gel to prepare affinity adsorbent. The crude extract of wheat germ was freezedried by affinity chromatography. The physicochemical properties were analyzed by SDSpolyacrylamide gel electrophoresis and isoelectric focusing electrophoresis. And the relative molecular mass and isoelectric point of wheat germ agglutinin were obtained, and the high efficiency of purification of wheat germ agglutinin was proved by affinity chromatography.

Extragonadal Germ Cell Cancer (EGC)

MedlinePlus

The Testicular Cancer Resource Center Extragonadal Germ Cell Cancer (EGC) 95% of all testicular tumors are germ cell tumors. That is, the tumors originate in the sperm forming cells in the testicles ( ...

Childhood Extracranial Germ Cell Tumors Treatment (PDQ®)—Patient Version

Cancer.gov

Childhood extracranial germ cell tumors treatment options include surgery, observation, and chemotherapy. Learn more about newly diagnosed and recurrent extracranial germ cell tumors in this expert-reviewed summary.

Germ Plasm Biogenesis--An Oskar-Centric Perspective.

PubMed

Lehmann, Ruth

2016-01-01

Germ granules are the hallmark of all germ cells. These membrane-less, electron-dense structures were first observed over 100 years ago. Today, their role in regulating and processing transcripts critical for the establishment, maintenance, and protection of germ cells is well established, and pathways outlining the biochemical mechanisms and physical properties associated with their biogenesis are emerging. © 2016 Elsevier Inc. All rights reserved.

Data imputation analysis for Cosmic Rays time series

NASA Astrophysics Data System (ADS)

Fernandes, R. C.; Lucio, P. S.; Fernandez, J. H.

2017-05-01

The occurrence of missing data concerning Galactic Cosmic Rays time series (GCR) is inevitable since loss of data is due to mechanical and human failure or technical problems and different periods of operation of GCR stations. The aim of this study was to perform multiple dataset imputation in order to depict the observational dataset. The study has used the monthly time series of GCR Climax (CLMX) and Roma (ROME) from 1960 to 2004 to simulate scenarios of 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80% and 90% of missing data compared to observed ROME series, with 50 replicates. Then, the CLMX station as a proxy for allocation of these scenarios was used. Three different methods for monthly dataset imputation were selected: AMÉLIA II - runs the bootstrap Expectation Maximization algorithm, MICE - runs an algorithm via Multivariate Imputation by Chained Equations and MTSDI - an Expectation Maximization algorithm-based method for imputation of missing values in multivariate normal time series. The synthetic time series compared with the observed ROME series has also been evaluated using several skill measures as such as RMSE, NRMSE, Agreement Index, R, R2, F-test and t-test. The results showed that for CLMX and ROME, the R2 and R statistics were equal to 0.98 and 0.96, respectively. It was observed that increases in the number of gaps generate loss of quality of the time series. Data imputation was more efficient with MTSDI method, with negligible errors and best skill coefficients. The results suggest a limit of about 60% of missing data for imputation, for monthly averages, no more than this. It is noteworthy that CLMX, ROME and KIEL stations present no missing data in the target period. This methodology allowed reconstructing 43 time series.

Results of Simulated Galactic Cosmic Radiation (GCR) and Solar Particle Events (SPE) on Spectra Restraint Fabric

NASA Technical Reports Server (NTRS)

Peters, Benjamin; Hussain, Sarosh; Waller, Jess

2017-01-01

Spectra or similar Ultra-high-molecular-weight polyethylene (UHMWPE) fabric is the likely choice for future structural space suit restraint materials due to its high strength-to-weight ratio, abrasion resistance, and dimensional stability. During long duration space missions, space suits will be subjected to significant amounts of high-energy radiation from several different sources. To insure that pressure garment designs properly account for effects of radiation, it is important to characterize the mechanical changes to structural materials after they have been irradiated. White Sands Test Facility (WSFTF) collaborated with the Crew and Thermal Systems Division at the Johnson Space Center (JSC) to irradiate and test various space suit materials by examining their tensile properties through blunt probe puncture testing and single fiber tensile testing after the materials had been dosed at various levels of simulated GCR and SPE Iron and Proton beams at Brookhaven National Laboratories. The dosages were chosen based on a simulation developed by the Structural Engineering Division at JSC for the expected radiation dosages seen by space suit softgoods seen on a Mars reference mission. Spectra fabric tested in the effort saw equivalent dosages at 2x, 10x, and 20x the predicted dose as well as a simulated 50 year exposure to examine the range of effects on the material and examine whether any degradation due to GCR would be present if the suit softgoods were stored in deep space for a long period of time. This paper presents the results of this work and outlines the impact on space suit pressure garment design for long duration deep space missions.

The Radiation Environment on the Surface of Mars and its Implications for Human Exploration: Five Years of Measurements with the MSL/RAD instrument

NASA Astrophysics Data System (ADS)

Ehresmann, B.; Zeitlin, C. J.; Hassler, D.; Wimmer-Schweingruber, R. F.; Guo, J.; Appel, J. K.; Boehm, E.; Boettcher, S. I.; Burmeister, S.; Lohf, H.; Martin-Garcia, C.; Matthiae, D.; Rafkin, S. C.; Reitz, G.

2017-12-01

NASA's Mars Science Laboratory (MSL) mission has now been operating in Gale Crater on the surface of Mars for five years. Onboard Curiosity, the Radiation Assessment Detector (MSL/RAD) is measuring the Martian surface radiation environment, providing insights into its intensity and composition. This radiation field is mainly composed of primary Galactic Cosmic Rays (GCRs) and secondary particles created by the GCRs' interactions with the Martian atmosphere and soil. On short time scales, the radiation environment can be dominated by contributions from Solar Energetic Particle (SEP) events. Due to the shielding effect of the Martian atmosphere, shapes and intensities of SEP spectra differ significantly between interplanetary space and the Martian surface. Understanding how SEP events influence the surface radiation field is crucial to assess associated health risks for potential human missions to Mars. Even in the absence of SEP events, the surface environment is influenced by solar activity, which determines the strength of the interplanetary magnetic field and modulates GCR intensities. The GCR flux has risen considerably since Curiosity's landing as the solar cycle heads towards minimum. Here, we present updated MSL/RAD results for charged particle fluxes measured on the surface from GCRs and SEP events from the five years of MSL operations on Mars. We will present results that incorporate updated analysis techniques for the MSL/RAD data and yield the most robust particle spectra to date. The GCR results will be compared to simulation results. The SEP-induced fluxes on the surface will be compared to measurements from other spacecraft in the inner heliosphere and, in particular, in Martian orbit.

Radiation Protection Effectiveness of Polymeric Based Shielding Materials at Low Earth Orbit

NASA Technical Reports Server (NTRS)

Badavi, Francis F.; Stewart-Sloan, Charlotte R.; Wilson, John W.; Adams, Daniel O.

2008-01-01

Correlations of limited ionizing radiation measurements onboard the Space Transportation System (STS; shuttle) and the International Space Station (ISS) with numerical simulations of charged particle transport through spacecraft structure have indicated that usage of hydrogen rich polymeric materials improves the radiation shielding performance of space structures as compared to the traditionally used aluminum alloys. We discuss herein the radiation shielding correlations between measurements on board STS-81 (Atlantis, 1997) using four polyethylene (PE) spheres of varying radii, and STS-89 (Endeavour, 1998) using aluminum alloy spheres; with numerical simulations of charged particle transport using the Langley Research Center (LaRC)-developed High charge (Z) and Energy TRaNsport (HZETRN) algorithm. In the simulations, the Galactic Cosmic Ray (GCR) component of the ionizing radiation environment at Low Earth Orbit (LEO) covering ions in the 1< or equals Z< or equals 28 range is represented by O'Neill's (2004) model. To compute the transmission coefficient for GCR ions at LEO, O'Neill's model is coupled with the angular dependent LaRC cutoff model. The trapped protons/electrons component of LEO environment is represented by a LaRC-developed time dependent procedure which couples the AP8min/AP8max, Deep River Neutron Monitor (DRNM) and F10.7 solar radio frequency measurements. The albedo neutron environment resulting from interaction of GCR ions with upper atmosphere is modeled through extrapolation of the Atmospheric Ionizing Radiation (AIR) measurements. With the validity of numerical simulations through correlation with PE and aluminum spheres measurements established, we further present results from the expansion of the simulations through the selection of high hydrogen content commercially available polymeric constituents such as PE foam core and Spectra fiber(Registered TradeMark) composite face sheet to assess their radiation shield properties as compared to generic PE.

Microstructure of warm rolling and pearlitic transformation of ultrafine-grained GCr15 steel

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

Sun, Jun-Jie; Lian, Fu-Liang; Liu, Hong-Ji

2014-09-15

Pearlitic transformation mechanisms have been investigated in ultra-fine grained GCr15 steel. The ultrafine-grained steel, whose grain size was less than 1 μm, was prepared by thermo-mechanical treatment at 873 K and then annealing at 923 K for 2 h. Pearlitic transformation was conducted by reheating the ultra-fine grained samples at 1073 K and 1123 K for different periods of time and then cooling in air. Scanning electron microscope observation shows that normal lamellar pearlite, instead of granular cementite and ferrite, cannot be formed when the grain size is approximately less than 4(± 0.6) μm, which yields a critical grain sizemore » for normal lamellar pearlitic transformations in this chromium alloyed steel. The result confirms that grain size has a great influence on pearlitic transformation by increasing the diffusion rate of carbon atoms in the ultra-fine grained steel, and the addition of chromium element doesn't change this pearlitic phase transformation rule. Meanwhile, the grain growth rate is reduced by chromium alloying, which is beneficial to form fine grains during austenitizing, thus it facilitating pearlitic transformation by divorced eutectoid transformation. Moreover, chromium element can form a relatively high gradient in the frontier of the undissolved carbide, which promotes carbide formation in the frontier of the undissolved carbide, i.e., chromium promotes divorced eutectoid transformation. - Highlights: • Ultrafine-grained GCr15 steel was obtained by warm rolling and annealing technology. • Reduction of grain size makes pearlite morphology from lamellar to granular. • Adding Cr does not change normal pearlitic phase transformation rule in UFG steel. • Cr carbide resists grain growth and facilitates pearlitic transformation by DET.« less

SALL4 EXPRESSION IN GERM CELL AND NON GERM-CELL TUMORS – A SYSTEMATIC IMMUNOHISTOCHEMICAL STUDY OF 3215 CASES

PubMed Central

Miettinen, Markku; Wang, Zengfeng; Mc. Cue, Peter A.; Sarlomo-Rikala, Maarit; Rys, Janusz; Biernat, Wojciech; Lasota, Jerzy; Lee, Yi-Shan

2014-01-01

SALL4 transcription factor is associated with embryonic cell pluripotency and has been shown as a useful immunohistochemical marker for germ cell tumors. However, information of SALL4 distribution in normal human tissues and non germ-cell tumors is limited. In this study we examined normal human tissues and 3215 tumors for SALL4 expression using a monoclonal antibody 6E3 and automated immunohistochemistry. In a 10th week embryo, SALL4 was expressed in ovocytes, intestine, kidney, and some hepatocytes. In adult tissues, it was only detected in germ cells. SALL4 was consistently expressed in all germ cell tumors except some trophoblastic tumors and mature components of teratomas, where it was selectively expressed in intestinal-like and some squamous epithelia. In non germ-cell carcinomas, SALL4 was detected in 20% of cases or more of serous carcinoma of ovary, urothelial high-grade carcinoma, and gastric adenocarcinoma (especially the intestinal type). SALL4 was only rarely (≤5%) expressed in mammary, colorectal, prostatic, and squamous cell carcinomas. Many SALL4 positive carcinomas showed poorly differentiated patterns and some showed positivity in most tumor cells mimicking the expression in germ cell tumors. SALL4 was commonly expressed in rhabdoid tumors of kidney and extrarenal sites, and in Wilms tumor. Expression of SALL4 was rare in other mesenchymal and neuroendocrine tumors but was occasionally detected in melanoma, desmoplastic small round cell tumor, epithelioid sarcoma, and rhabdomyosarcoma. All hematopoietic tumors were negative. SALL4 is an excellent marker of non-teratomatous germ cell tumors, but it is also expressed in other tumors, sometimes extensively. Such expression may reflect stem-cell like differentiation and must be considered when using SALL4 as a marker for germ cell tumors. Observed lack of other pluripotency factors, OCT4 and NANOG, in SALL4-positive non-germ cell tumors can also be diagnostically helpful. PMID:24525512

Combination Chemotherapy Followed by Bone Marrow Transplantation in Treating Patients With Rare Cancer

ClinicalTrials.gov

2013-06-20

Childhood Germ Cell Tumor; Extragonadal Germ Cell Tumor; Head and Neck Cancer; Kidney Cancer; Liver Cancer; Lymphoma; Neuroblastoma; Ovarian Cancer; Retinoblastoma; Sarcoma; Testicular Germ Cell Tumor

Ovarian Germ Cell Tumors Treatment (PDQ®)—Health Professional Version

Cancer.gov

Ovarian germ cell tumors treatment options include surgery, chemotherapy, and radiation therapy. Get detailed treatment information for newly diagnosed or recurrent germ cell tumors in this summary for clinicians.

A germ cell determinant reveals parallel pathways for germ line development in Caenorhabditis elegans.

PubMed

Mainpal, Rana; Nance, Jeremy; Yanowitz, Judith L

2015-10-15

Despite the central importance of germ cells for transmission of genetic material, our understanding of the molecular programs that control primordial germ cell (PGC) specification and differentiation are limited. Here, we present findings that X chromosome NonDisjunction factor-1 (XND-1), known for its role in regulating meiotic crossover formation, is an early determinant of germ cell fates in Caenorhabditis elegans. xnd-1 mutant embryos display a novel 'one PGC' phenotype as a result of G2 cell cycle arrest of the P4 blastomere. Larvae and adults display smaller germ lines and reduced brood size consistent with a role for XND-1 in germ cell proliferation. Maternal XND-1 proteins are found in the P4 lineage and are exclusively localized to the nucleus in PGCs, Z2 and Z3. Zygotic XND-1 turns on shortly thereafter, at the ∼300-cell stage, making XND-1 the earliest zygotically expressed gene in worm PGCs. Strikingly, a subset of xnd-1 mutants lack germ cells, a phenotype shared with nos-2, a member of the conserved Nanos family of germline determinants. We generated a nos-2 null allele and show that nos-2; xnd-1 double mutants display synthetic sterility. Further removal of nos-1 leads to almost complete sterility, with the vast majority of animals without germ cells. Sterility in xnd-1 mutants is correlated with an increase in transcriptional activation-associated histone modification and aberrant expression of somatic transgenes. Together, these data strongly suggest that xnd-1 defines a new branch for PGC development that functions redundantly with nos-2 and nos-1 to promote germline fates by maintaining transcriptional quiescence and regulating germ cell proliferation. © 2015. Published by The Company of Biologists Ltd.

Zebrafish Staufen1 and Staufen2 are required for the survival and migration of primordial germ cells.

PubMed

Ramasamy, Srinivas; Wang, Hui; Quach, Helen Ngoc Bao; Sampath, Karuna

2006-04-15

In sexually reproducing organisms, primordial germ cells (PGCs) give rise to the cells of the germ line, the gametes. In many animals, PGCs are set apart from somatic cells early during embryogenesis. Work in Drosophila, C. elegans, Xenopus, and zebrafish has shown that maternally provided localized cytoplasmic determinants specify the germ line in these organisms (Raz, E., 2003. Primordial germ-cell development: the zebrafish perspective. Nat. Rev., Genet. 4, 690--700; Santos, A.C., Lehmann, R., 2004. Germ cell specification and migration in Drosophila and beyond. Curr. Biol. 14, R578-R589). The Drosophila RNA-binding protein, Staufen is required for germ cell formation, and mutations in stau result in a maternal effect grandchild-less phenotype (Schupbach,T., Weischaus, E., 1989. Female sterile mutations on the second chromosome of Drosophila melanogaster:1. Maternal effect mutations. Genetics 121, 101-17). Here we describe the functions of two zebrafish Staufen-related proteins, Stau1 and Stau2. When Stau1 or Stau2 functions are compromised in embryos by injecting antisense morpholino modified oligonucleotides or dominant-negative Stau peptides, germ layer patterning is not affected. However, expression of the PGC marker vasa is not maintained. Furthermore, expression of a green fluorescent protein (GFP):nanos 3'UTR fusion protein in germ cells shows that PGC migration is aberrant, and the mis-migrating PGCs do not survive in Stau-compromised embryos. Stau2 is also required for survival of neurons in the central nervous system (CNS). These phenotypes are rescued by co-injection of Drosophila stau mRNA. Thus, staufen has an evolutionarily conserved function in germ cells. In addition, we have identified a function for Stau proteins in PGC migration.

Comparison of Model Calculations of Biological Damage from Exposure to Heavy Ions with Measurements

NASA Astrophysics Data System (ADS)

Kim, Myung-Hee Y.; Wu, Honglu; Hada, Megumi; Cucinotta, Francis

The space environment consists of a varying field of radiation particles including high-energy ions, with spacecraft shielding material providing the major protection to astronauts from harmful exposure. Unlike low-LET g or X rays, the presence of shielding does not always reduce the radiation risks for energetic charged-particle exposure. Dose delivered by the charged particle increases sharply at the Bragg peak. However, the Bragg curve does not necessarily represent the biological damage along the particle path since biological effects are influenced by the track structures of both primary and secondary particles. Therefore, the ‘‘biological Bragg curve’’ is dependent on the energy and the type of the primary particle and may vary for different biological end points. Measurements of the induction of micronuclei (MN) have made across the Bragg curve in human fibroblasts exposed to energetic silicon and iron ions in vitro at two different energies, 300 MeV/nucleon and 1 GeV/nucleon. Although the data did not reveal an increased yield of MN at the location of the Bragg peak, the increased inhibition of cell progression, which is related to cell death, was found at the Bragg peak location. These results are compared to the calculations of biological damage using a stochastic Monte-Carlo track structure model, Galactic Cosmic Ray Event-based Risk Model (GERM) code (Cucinotta et al., 2011). The GERM code estimates the basic physical properties along the passage of heavy ions in tissue and shielding materials, by which the experimental set-up can be interpreted. The code can also be used to describe the biophysical events of interest in radiobiology, cancer therapy, and space exploration. The calculation has shown that the severely damaged cells at the Bragg peak are more likely to go through reproductive death, the so called “overkill”. F. A. Cucinotta, I. Plante, A. L. Ponomarev, and M. Y. Kim, Nuclear Interactions in Heavy Ion Transport and Event-based Risk Models, Radiation Protection Dosimetry, 143 (2-4), 384-390, 2011, doi:10.1093/rpd/ncq512

Ovarian Germ Cell Tumors Treatment

MedlinePlus

... Tube, & Primary Peritoneal Cancer Screening Research Ovarian Germ Cell Tumors Treatment (PDQ®)–Patient Version Treatment Option Overview ... types of treatment for patients with ovarian germ cell tumors. Different types of treatment are available for ...

Germ Cells Are Not Required to Establish the Female Pathway in Mouse Fetal Gonads

PubMed Central

Maatouk, Danielle M.; Mork, Lindsey; Hinson, Ashley; Kobayashi, Akio; McMahon, Andrew P.; Capel, Blanche

2012-01-01

The fetal gonad is composed of a mixture of somatic cell lineages and germ cells. The fate of the gonad, male or female, is determined by a population of somatic cells that differentiate into Sertoli or granulosa cells and direct testis or ovary development. It is well established that germ cells are not required for the establishment or maintenance of Sertoli cells or testis cords in the male gonad. However, in the agametic ovary, follicles do not form suggesting that germ cells may influence granulosa cell development. Prior investigations of ovaries in which pre-meiotic germ cells were ablated during fetal life reported no histological changes during stages prior to birth. However, whether granulosa cells underwent normal molecular differentiation was not investigated. In cases where germ cell loss occurred secondary to other mutations, transdifferentiation of granulosa cells towards a Sertoli cell fate was observed, raising questions about whether germ cells play an active role in establishing or maintaining the fate of granulosa cells. We developed a group of molecular markers associated with ovarian development, and show here that the loss of pre-meiotic germ cells does not disrupt the somatic ovarian differentiation program during fetal life, or cause transdifferentiation as defined by expression of Sertoli markers. Since we do not find defects in the ovarian somatic program, the subsequent failure to form follicles at perinatal stages is likely attributable to the absence of germ cells rather than to defects in the somatic cells. PMID:23091613

Immature germ cells in semen - correlation with total sperm count and sperm motility.

PubMed

Patil, Priya S; Humbarwadi, Rajendra S; Patil, Ashalata D; Gune, Anita R

2013-07-01

Current data regarding infertility suggests that male factor contributes up to 30% of the total cases of infertility. Semen analysis reveals the presence of spermatozoa as well as a number of non-sperm cells, presently being mentioned in routine semen report as "round cells" without further differentiating them into leucocytes or immature germ cells. The aim of this work was to study a simple, cost-effective, and convenient method for differentiating the round cells in semen into immature germ cells and leucocytes and correlating them with total sperm counts and motility. Semen samples from 120 males, who had come for investigation for infertility, were collected, semen parameters recorded, and stained smears studied for different round cells. Statistical analysis of the data was done to correlate total sperm counts and sperm motility with the occurrence of immature germ cells and leucocytes. The average shedding of immature germ cells in different groups with normal and low sperm counts was compared. The clinical significance of "round cells" in semen and their differentiation into leucocytes and immature germ cells are discussed. Round cells in semen can be differentiated into immature germ cells and leucocytes using simple staining methods. The differential counts mentioned in a semen report give valuable and clinically relevant information. In this study, we observed a negative correlation between total count and immature germ cells, as well as sperm motility and shedding of immature germ cells. The latter was statistically significant with a P value 0.000.

Germ line determinants are not localized early in sea urchin development, but do accumulate in the small micromere lineage.

PubMed

Juliano, Celina E; Voronina, Ekaterina; Stack, Christie; Aldrich, Maryanna; Cameron, Andrew R; Wessel, Gary M

2006-12-01

Two distinct modes of germ line determination are used throughout the animal kingdom: conditional-an inductive mechanism, and autonomous-an inheritance of maternal factors in early development. This study identifies homologs of germ line determinants in the sea urchin Strongylocentrotus purpuratus to examine its mechanism of germ line determination. A list of conserved germ-line associated genes from diverse organisms was assembled to search the S. purpuratus genome for homologs, and the expression patterns of these genes were examined during embryogenesis by whole mount in situ RNA hybridization and QPCR. Of the 14 genes tested, all transcripts accumulate uniformly during oogenesis and Sp-pumilio, Sp-tudor, Sp-MSY, and Sp-CPEB1 transcripts are also uniformly distributed during embryonic development. Sp-nanos2, Sp-seawi, and Sp-ovo transcripts, however, are enriched in the vegetal plate of the mesenchyme blastula stage and Sp-vasa, Sp-nanos2, Sp-seawi, and Sp-SoxE transcripts are localized in small micromere descendents at the tip of the archenteron during gastrulation and are then enriched in the left coelomic pouch of larvae. The results of this screen suggest that sea urchins conditionally specify their germ line, and support the hypothesis that this mechanism is the basal mode of germ line determination amongst deuterostomes. Furthermore, accumulation of germ line determinants selectively in small micromere descendents supports the hypothesis that these cells contribute to the germ line.

HENMT1 and piRNA Stability Are Required for Adult Male Germ Cell Transposon Repression and to Define the Spermatogenic Program in the Mouse

PubMed Central

Lim, Shu Ly; Geoghegan, Joel; Hempfling, Anna-Lena; Bergmann, Martin; Goodnow, Christopher C.; Ormandy, Christopher J.; Wong, Lee; Mann, Jeff; Scott, Hamish S.; Jamsai, Duangporn; Adelson, David L.

2015-01-01

piRNAs are critical for transposable element (TE) repression and germ cell survival during the early phases of spermatogenesis, however, their role in adult germ cells and the relative importance of piRNA methylation is poorly defined in mammals. Using a mouse model of HEN methyltransferase 1 (HENMT1) loss-of-function, RNA-Seq and a range of RNA assays we show that HENMT1 is required for the 2’ O-methylation of mammalian piRNAs. HENMT1 loss leads to piRNA instability, reduced piRNA bulk and length, and ultimately male sterility characterized by a germ cell arrest at the elongating germ cell phase of spermatogenesis. HENMT1 loss-of-function, and the concomitant loss of piRNAs, resulted in TE de-repression in adult meiotic and haploid germ cells, and the precocious, and selective, expression of many haploid-transcripts in meiotic cells. Precocious expression was associated with a more active chromatin state in meiotic cells, elevated levels of DNA damage and a catastrophic deregulation of the haploid germ cell gene expression. Collectively these results define a critical role for HENMT1 and piRNAs in the maintenance of TE repression in adult germ cells and setting the spermatogenic program. PMID:26496356

Wear Resistance Enhancement of Ti-6Al-4 V Alloy by Applying Zr-Modified Silicide Coatings

NASA Astrophysics Data System (ADS)

Li, Xuan; Hu, Guangzhong; Tian, Jin; Tian, Wei; Xie, Wenling; Li, Xiulan

2018-03-01

Zr-modified silicide coatings were prepared on Ti-6Al-4 V alloy by pack cementation process to enhance its wear resistance. The microstructure and wear properties of the substrate and the coatings were comparatively investigated using GCr15 and Al2O3 as the counterparts under different sliding loads. The obtained Zr-modified silicide coating had a multilayer structure, consisting of a thick (Ti, X)Si2 (X represents Al, Zr and V elements) outer layer, a TiSi middle layer and a Ti5Si4 + Ti5Si3 inner layer. The micro-hardness of the coating was much higher than the substrate and displayed a decrease tendency from the coating surface to the interior. Sliding against either GCr15 or Al2O3 balls, the coatings showed superior anti-friction property to the Ti-6Al-4 V alloy, as confirmed by its much lower wear rate under each employed sliding condition.

Getting ready for the manned mission to Mars: the astronauts' risk from space radiation

NASA Astrophysics Data System (ADS)

Hellweg, Christine E.; Baumstark-Khan, Christa

2007-07-01

Space programmes are shifting towards planetary exploration and, in particular, towards missions by human beings to the Moon and to Mars. Radiation is considered to be one of the major hazards for personnel in space and has emerged as the most critical issue to be resolved for long-term missions both orbital and interplanetary. The two cosmic sources of radiation that could impact a mission outside the Earth’s magnetic field are solar particle events (SPE) and galactic cosmic rays (GCR). Exposure to the types of ionizing radiation encountered during space travel may cause a number of health-related problems, but the primary concern is related to the increased risk of cancer induction in astronauts. Predictions of cancer risk and acceptable radiation exposure in space are extrapolated from minimal data and are subject to many uncertainties. The paper describes present-day estimates of equivalent doses from GCR and solar cosmic radiation behind various shields and radiation risks for astronauts on a mission to Mars.

Effects of radiobiological uncertainty on vehicle and habitat shield design for missions to the moon and Mars

NASA Technical Reports Server (NTRS)

Wilson, John W.; Nealy, John E.; Schimmerling, Walter; Cucinotta, Francis A.; Wood, James S.

1993-01-01

Some consequences of uncertainties in radiobiological risk due to galactic cosmic ray (GCR) exposure are analyzed for their effect on engineering designs for the first lunar outpost and a mission to explore Mars. This report presents the plausible effect of biological uncertainties, the design changes necessary to reduce the uncertainties to acceptable levels for a safe mission, and an evaluation of the mission redesign cost. Estimates of the amount of shield mass required to compensate for radiobiological uncertainty are given for a simplified vehicle and habitat. The additional amount of shield mass required to provide a safety factor for uncertainty compensation is calculated from the expected response to GCR exposure. The amount of shield mass greatly increases in the estimated range of biological uncertainty, thus, escalating the estimated cost of the mission. The estimates are used as a quantitative example for the cost-effectiveness of research in radiation biophysics and radiation physics.

Radiation Effects and Protection for Moon and Mars Missions

NASA Technical Reports Server (NTRS)

Parnell, Thomas A.; Watts, John W., Jr.; Armstrong, Tony W.

1998-01-01

Manned and robotic missions to the Earth's moon and Mars are exposed to a continuous flux of Galactic Cosmic Rays (GCR) and occasional, but intense, fluxes of Solar Energetic Particles (SEP). These natural radiations impose hazards to manned exploration, but also present some constraints to the design of robotic missions. The hazards to interplanetary flight crews and their uncertainties have been studied recently by a National Research Council Committee (Space Studies Board 1996). Considering the present uncertainty estimates, thick spacecraft shielding would be needed for manned missions, some of which could be accomplished with onboard equipment and expendables. For manned and robotic missions, the effects of radiation on electronics, sensors, and controls require special consideration in spacecraft design. This paper describes the GCR and SEP particle fluxes, secondary particles behind shielding, uncertainties in radiobiological effects and their impact on manned spacecraft design, as well as the major effects on spacecraft equipment. The principal calculational tools and considerations to mitigate the radiation effects are discussed, and work in progress to reduce uncertainties is included.

A 21.7 kb DNA segment on the left arm of yeast chromosome XIV carries WHI3, GCR2, SPX18, SPX19, an homologue to the heat shock gene SSB1 and 8 new open reading frames of unknown function.

PubMed

Jonniaux, J L; Coster, F; Purnelle, B; Goffeau, A

1994-12-01

We report the amino acid sequence of 13 open reading frames (ORF > 299 bp) located on a 21.7 kb DNA segment from the left arm of chromosome XIV of Saccharomyces cerevisiae. Five open reading frames had been entirely or partially sequenced previously: WHI3, GCR2, SPX19, SPX18 and a heat shock gene similar to SSB1. The products of 8 other ORFs are new putative proteins among which N1394 is probably a membrane protein. N1346 contains a leucine zipper pattern and the corresponding ORF presents an HAP (global regulator of respiratory genes) upstream activating sequence in the promoting region. N1386 shares homologies with the DNA structure-specific recognition protein family SSRPs and the corresponding ORF is preceded by an MCB (MluI cell cycle box) upstream activating factor.

Visualization of Radiation Environment on Mars: Assessment with MARIE Measurements

NASA Technical Reports Server (NTRS)

Saganti, P.; Cucinotta, F.; Zeitlin, C.; Cleghorn, T.; Flanders, J.; Riman, F.; Hu, X.; Pinsky, L.; Lee, K.; Anderson, V.;

Cermet coating tribological behavior in high temperature helium

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

CACHON, Lionel; ALBALADEJO, Serge; TARAUD, Pascal

As the CEA is highly involved in the Generation IV Forum, a comprehensive research and development program has been conducted for several years, in order to establish the feasibility of Gas Cooled Reactor (GCR) technology projects using helium as a cooling fluid. Within this framework, a tribology program was launched in order to select and qualify coatings and materials, and to provide recommendations for the sliding components operating in GCRs. The purpose of this paper is to describe the CEA Helium tribology study on several GCR components (thermal barriers, control rod drive mechanisms, reactor internals, ..) requiring protection against wearmore » and bonding. Tests in helium atmosphere are necessary to be fully representative of tribological environments and to assess the material or coating candidates which can provide a reliable answer to these situations. This paper focuses on the tribology tests performed on CERMET (Cr{sub 3}C-2- NiCr) coatings within a temperature range of between 800 and 1000 deg C.« less

Getting ready for the manned mission to Mars: the astronauts' risk from space radiation.

PubMed

Hellweg, Christine E; Baumstark-Khan, Christa

2007-07-01

Space programmes are shifting towards planetary exploration and, in particular, towards missions by human beings to the Moon and to Mars. Radiation is considered to be one of the major hazards for personnel in space and has emerged as the most critical issue to be resolved for long-term missions both orbital and interplanetary. The two cosmic sources of radiation that could impact a mission outside the Earth's magnetic field are solar particle events (SPE) and galactic cosmic rays (GCR). Exposure to the types of ionizing radiation encountered during space travel may cause a number of health-related problems, but the primary concern is related to the increased risk of cancer induction in astronauts. Predictions of cancer risk and acceptable radiation exposure in space are extrapolated from minimal data and are subject to many uncertainties. The paper describes present-day estimates of equivalent doses from GCR and solar cosmic radiation behind various shields and radiation risks for astronauts on a mission to Mars.

General Information about Extragonadal Germ Cell Tumors

MedlinePlus

... Germ Cell Tumors Treatment (PDQ®)–Patient Version General Information About Extragonadal Germ Cell Tumors Go to Health ... the PDQ Adult Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

General Information about Childhood Extracranial Germ Cell Tumors

MedlinePlus

... Germ Cell Tumors Treatment (PDQ®)–Patient Version General Information About Childhood Extracranial Germ Cell Tumors Go to ... the PDQ Pediatric Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

Treatment Option Overview (Ovarian Germ Cell Tumors)

MedlinePlus

... Tube, & Primary Peritoneal Cancer Screening Research Ovarian Germ Cell Tumors Treatment (PDQ®)–Patient Version Treatment Option Overview ... types of treatment for patients with ovarian germ cell tumors. Different types of treatment are available for ...

Treatment Options By Stage (Ovarian Germ Cell Tumors)

MedlinePlus

... Tube, & Primary Peritoneal Cancer Screening Research Ovarian Germ Cell Tumors Treatment (PDQ®)–Patient Version Treatment Option Overview ... types of treatment for patients with ovarian germ cell tumors. Different types of treatment are available for ...

Development without germ cells: the role of the germ line in zebrafish sex differentiation.

PubMed

Slanchev, Krasimir; Stebler, Jürg; de la Cueva-Méndez, Guillermo; Raz, Erez

2005-03-15

The progenitors of the gametes, the primordial germ cells (PGCs) are typically specified early in the development in positions, which are distinct from the gonad. These cells then migrate toward the gonad where they differentiate into sperms and eggs. Here, we study the role of the germ cells in somatic development and particularly the role of the germ line in the sex differentiation in zebrafish. To this end, we ablated the germ cells using two independent methods and followed the development of the experimental fish. First, PGCs were ablated by knocking down the function of dead end, a gene important for the survival of this lineage. Second, a method to eliminate the PGCs using the toxin-antitoxin components of the parD bacterial genetic system was used. Specifically, we expressed a bacterial toxin Kid preferentially in the PGCs and at the same time protected somatic cells by uniformly expressing the specific antidote Kis. Our results demonstrate an unexpected role for the germ line in promoting female development because PGC-ablated fish invariably developed as males.

Development without germ cells: The role of the germ line in zebrafish sex differentiation

PubMed Central

Slanchev, Krasimir; Stebler, Jürg; de la Cueva-Méndez, Guillermo; Raz, Erez

2005-01-01

The progenitors of the gametes, the primordial germ cells (PGCs) are typically specified early in the development in positions, which are distinct from the gonad. These cells then migrate toward the gonad where they differentiate into sperms and eggs. Here, we study the role of the germ cells in somatic development and particularly the role of the germ line in the sex differentiation in zebrafish. To this end, we ablated the germ cells using two independent methods and followed the development of the experimental fish. First, PGCs were ablated by knocking down the function of dead end, a gene important for the survival of this lineage. Second, a method to eliminate the PGCs using the toxin–antitoxin components of the parD bacterial genetic system was used. Specifically, we expressed a bacterial toxin Kid preferentially in the PGCs and at the same time protected somatic cells by uniformly expressing the specific antidote Kis. Our results demonstrate an unexpected role for the germ line in promoting female development because PGC-ablated fish invariably developed as males. PMID:15728735

Use of Stirred Suspension Bioreactors for Male Germ Cell Enrichment.

PubMed

Sakib, Sadman; Dores, Camila; Rancourt, Derrick; Dobrinski, Ina

2016-01-01

Spermatogenesis is a stem cell based system. Both therapeutic and biomedical research applications of spermatogonial stem cells require a large number of cells. However, there are only few germ line stem cells in the testis, contained in the fraction of undifferentiated spermatogonia. The lack of specific markers makes it difficult to isolate these cells. The long term maintenance and proliferation of nonrodent germ cells in culture has so far been met with limited success, partially due to the lack of highly enriched starting populations. Differential plating, which depends on the differential adhesion properties of testicular somatic and germ cells to tissue culture dishes, has been the method of choice for germ cell enrichment, especially for nonrodent germ cells. However, for large animals, this process becomes labor intensive and increases variability due to the need for extensive handling. Here, we describe the use of stirred suspension bioreactors, as a novel system for enriching undifferentiated germ cells from 1-week-old pigs. This method capitalizes on the adherent properties of somatic cells within a controlled environment, thus promoting the enrichment of progenitor cells with minimal handling and variability.

PIE-1 is a bifunctional protein that regulates maternal and zygotic gene expression in the embryonic germ line of Caenorhabditis elegans

PubMed Central

Tenenhaus, Christina; Subramaniam, Kuppuswamy; Dunn, Melanie A.; Seydoux, Geraldine

2001-01-01

The CCCH zinc finger protein PIE-1 is an essential regulator of germ cell fate that segregates with the germ lineage during the first cleavages of the Caenorhabditis elegans embryo. We have shown previously that one function of PIE-1 is to inhibit mRNA transcription. Here we show that PIE-1 has a second function in germ cells; it is required for efficient expression of the maternally encoded Nanos homolog NOS-2. This second function is genetically separable from PIE-1's inhibitory effect on transcription. A mutation in PIE-1's second CCCH finger reduces NOS-2 expression without affecting transcriptional repression and causes primordial germ cells to stray away from the somatic gonad, occasionally exiting the embryo entirely. Our results indicate that PIE-1 promotes germ cell fate by two independent mechanisms as follows: (1) inhibition of transcription, which blocks zygotic programs that drive somatic development, and (2) activation of protein expression from nos-2 and possibly other maternal RNAs, which promotes primordial germ cell development. PMID:11316796

In vitro gamete derivation from pluripotent stem cells: progress and perspective.

PubMed

Nagano, Makoto C

2007-04-01

Germ cells constitute a highly specialized cell population that is indispensable for the continuation and evolution of the species. Recently, several research groups have shown that these unique cells can be produced in vitro from pluripotent stem cells. Furthermore, live births of offspring using induced germ cells have been reported in one study. These results suggest that it may be possible to investigate germ cell development ex vivo and to establish novel reproductive technologies. To this end, it is critical to assess if gamete induction processes in vitro faithfully recapitulate normal germ cell development in vivo. Here, this issue is discussed with a focus on the germ line specification and the sex-specific development of pre- and postnatal germ cells. The aim of this paper is to concisely summarize the past progress and to present some future issues for the investigation into in vitro gamete production from pluripotent stem cells.

Forces directing germ-band extension in Drosophila embryos.

PubMed

Kong, Deqing; Wolf, Fred; Großhans, Jörg

2017-04-01

Body axis elongation by convergent extension is a conserved developmental process found in all metazoans. Drosophila embryonic germ-band extension is an important morphogenetic process during embryogenesis, by which the length of the germ-band is more than doubled along the anterior-posterior axis. This lengthening is achieved by typical convergent extension, i.e. narrowing the lateral epidermis along the dorsal-ventral axis and simultaneous extension along the anterior-posterior axis. Germ-band extension is largely driven by cell intercalation, whose directionality is determined by the planar polarity of the tissue and ultimately by the anterior-posterior patterning system. In addition, extrinsic tensile forces originating from the invaginating endoderm induce cell shape changes, which transiently contribute to germ-band extension. Here, we review recent progress in understanding of the role of mechanical forces in germ-band extension. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Production of maternal-zygotic mutant zebrafish by germ-line replacement.

PubMed

Ciruna, Brian; Weidinger, Gilbert; Knaut, Holger; Thisse, Bernard; Thisse, Christine; Raz, Erez; Schier, Alexander F

2002-11-12

We report a generally applicable strategy for transferring zygotic lethal mutations through the zebrafish germ line. By using a morpholino oligonucleotide that blocks primordial germ cell (PGC) development, we generate embryos devoid of endogenous PGCs to serve as hosts for the transplantation of germ cells derived from homozygous mutant donors. Successful transfers are identified by the localization of specifically labeled donor PGCs to the region of the developing gonad in chimeric embryos. This strategy, which results in the complete replacement of the host germ line with donor PGCs, was validated by the generation of maternal and maternal-zygotic mutants for the miles apart locus. This germ-line replacement technique provides a powerful tool for studying the maternal effects of zygotic lethal mutations. Furthermore, the ability to generate large clutches of purely mutant embryos will greatly facilitate embryological, genetic, genomic, and biochemical studies.

Production of maternal-zygotic mutant zebrafish by germ-line replacement

PubMed Central

Ciruna, Brian; Weidinger, Gilbert; Knaut, Holger; Thisse, Bernard; Thisse, Christine; Raz, Erez; Schier, Alexander F.

2002-01-01

We report a generally applicable strategy for transferring zygotic lethal mutations through the zebrafish germ line. By using a morpholino oligonucleotide that blocks primordial germ cell (PGC) development, we generate embryos devoid of endogenous PGCs to serve as hosts for the transplantation of germ cells derived from homozygous mutant donors. Successful transfers are identified by the localization of specifically labeled donor PGCs to the region of the developing gonad in chimeric embryos. This strategy, which results in the complete replacement of the host germ line with donor PGCs, was validated by the generation of maternal and maternal-zygotic mutants for the miles apart locus. This germ-line replacement technique provides a powerful tool for studying the maternal effects of zygotic lethal mutations. Furthermore, the ability to generate large clutches of purely mutant embryos will greatly facilitate embryological, genetic, genomic, and biochemical studies. PMID:12397179

Mammalian X Chromosome Dosage Compensation: Perspectives From the Germ Line.

PubMed

Sangrithi, Mahesh N; Turner, James M A

2018-06-01

Sex chromosomes are advantageous to mammals, allowing them to adopt a genetic rather than environmental sex determination system. However, sex chromosome evolution also carries a burden, because it results in an imbalance in gene dosage between females (XX) and males (XY). This imbalance is resolved by X dosage compensation, which comprises both X chromosome inactivation and X chromosome upregulation. X dosage compensation has been well characterized in the soma, but not in the germ line. Germ cells face a special challenge, because genome wide reprogramming erases epigenetic marks responsible for maintaining the X dosage compensated state. Here we explain how evolution has influenced the gene content and germ line specialization of the mammalian sex chromosomes. We discuss new research uncovering unusual X dosage compensation states in germ cells, which we postulate influence sexual dimorphisms in germ line development and cause infertility in individuals with sex chromosome aneuploidy. © 2018 The Authors. BioEssays Published by Periodicals, Inc.

Commitment Predictors: Long-Distance versus Geographically Close Relationships

ERIC Educational Resources Information Center

Pistole, M. Carole; Roberts, Amber; Mosko, Jonathan E.

2010-01-01

In this web-based study, the authors examined long-distance relationships (LDRs) and geographically close relationships (GCRs). Two hierarchical multiple regressions (N = 138) indicated that attachment predicted LDR and GCR commitment in Step 1. Final equations indicated that high satisfaction and investments predicted LDR commitment, whereas low…

Posterior localization of ApVas1 positions the preformed germ plasm in the sexual oviparous pea aphid Acyrthosiphon pisum

PubMed Central

2014-01-01

Background Germline specification in some animals is driven by the maternally inherited germ plasm during early embryogenesis (inheritance mode), whereas in others it is induced by signals from neighboring cells in mid or late development (induction mode). In the Metazoa, the induction mode appears as a more prevalent and ancestral condition; the inheritance mode is therefore derived. However, regarding germline specification in organisms with asexual and sexual reproduction it has not been clear whether both strategies are used, one for each reproductive phase, or if just one strategy is used for both phases. Previously we have demonstrated that specification of germ cells in the asexual viviparous pea aphid depends on a preformed germ plasm. In this study, we extended this work to investigate how germ cells were specified in the sexual oviparous embryos, aiming to understand whether or not developmental plasticity of germline specification exists in the pea aphid. Results We employed Apvas1, a Drosophila vasa ortholog in the pea aphid, as a germline marker to examine whether germ plasm is preformed during oviparous development, as has already been seen in the viviparous embryos. During oogenesis, Apvas1 mRNA and ApVas1 protein were both evenly distributed. After fertilization, uniform expression of Apvas1 remained in the egg but posterior localization of ApVas1 occurred from the fifth nuclear cycle onward. Posterior co-localization of Apvas1/ApVas1 was first identified in the syncytial blastoderm undergoing cellularization, and later we could detect specific expression of Apvas1/ApVas1 in the morphologically identifiable germ cells of mature embryos. This suggests that Apvas1/ApVas1-positive cells are primordial germ cells and posterior localization of ApVas1 prior to cellularization positions the preformed germ plasm. Conclusions We conclude that both asexual and sexual pea aphids rely on the preformed germ plasm to specify germ cells and that developmental plasticity of germline specification, unlike axis patterning, occurs in neither of the two aphid reproductive phases. Consequently, the maternal inheritance mode implicated by a preformed germ plasm in the oviparous pea aphid becomes a non-canonical case in the Hemimetabola, where so far the zygotic induction mode prevails in most other studied insects. PMID:24855557

Germ cells are not the primary factor for sexual fate determination in goldfish.

PubMed

Goto, Rie; Saito, Taiju; Takeda, Takahiro; Fujimoto, Takafumi; Takagi, Misae; Arai, Katsutoshi; Yamaha, Etsuto

2012-10-01

The presence of germ cells in the early gonad is important for sexual fate determination and gonadal development in vertebrates. Recent studies in zebrafish and medaka have shown that a lack of germ cells in the early gonad induces sex reversal in favor of a male phenotype. However, it is uncertain whether the gonadal somatic cells or the germ cells are predominant in determining gonadal fate in other vertebrate. Here, we investigated the role of germ cells in gonadal differentiation in goldfish, a gonochoristic species that possesses an XX-XY genetic sex determination system. The primordial germ cells (PGCs) of the fish were eliminated during embryogenesis by injection of a morpholino oligonucleotide against the dead end gene. Fish without germ cells showed two types of gonadal morphology: one with an ovarian cavity; the other with seminiferous tubules. Next, we tested whether function could be restored to these empty gonads by transplantation of a single PGC into each embryo, and also determined the gonadal sex of the resulting germline chimeras. Transplantation of a single GFP-labeled PGC successfully produced a germline chimera in 42.7% of the embryos. Some of the adult germline chimeras had a developed gonad on one side that contained donor derived germ cells, while the contralateral gonad lacked any early germ cell stages. Female germline chimeras possessed a normal ovary and a germ-cell free ovary-like structure on the contralateral side; this structure was similar to those seen in female morphants. Male germline chimeras possessed a testis and a contralateral empty testis that contained some sperm in the tubular lumens. Analysis of aromatase, foxl2 and amh expression in gonads of morphants and germline chimeras suggested that somatic transdifferentiation did not occur. The offspring of fertile germline chimeras all had the donor-derived phenotype, indicating that germline replacement had occurred and that the transplanted PGC had rescued both female and male gonadal function. These findings suggest that the absence of germ cells did not affect the pathway for ovary or testis development and that phenotypic sex in goldfish is determined by somatic cells under genetic sex control rather than an interaction between the germ cells and somatic cells. Copyright © 2012 Elsevier Inc. All rights reserved.

Specifying and protecting germ cell fate

PubMed Central

Strome, Susan; Updike, Dustin

2015-01-01

Germ cells are the special cells in the body that undergo meiosis to generate gametes and subsequently entire new organisms after fertilization, a process that continues generation after generation. Recent studies have expanded our understanding of the factors and mechanisms that specify germ cell fate, including the partitioning of maternally supplied ‘germ plasm’, inheritance of epigenetic memory and expression of transcription factors crucial for primordial germ cell (PGC) development. Even after PGCs are specified, germline fate is labile and thus requires protective mechanisms, such as global transcriptional repression, chromatin state alteration and translation of only germline-appropriate transcripts. Findings from diverse species continue to provide insights into the shared and divergent needs of these special reproductive cells. PMID:26122616

Oxaliplatin in Treating Young Patients With Recurrent Solid Tumors That Have Not Responded to Previous Treatment

ClinicalTrials.gov

2013-06-04

Childhood Central Nervous System Germ Cell Tumor; Childhood Extragonadal Germ Cell Tumor; Childhood Hepatoblastoma; Childhood Hepatocellular Carcinoma; Childhood High-grade Cerebral Astrocytoma; Childhood Low-grade Cerebral Astrocytoma; Childhood Malignant Ovarian Germ Cell Tumor; Childhood Malignant Testicular Germ Cell Tumor; Childhood Teratoma; Recurrent Adrenocortical Carcinoma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Liver Cancer; Recurrent Childhood Malignant Germ Cell Tumor; Recurrent Childhood Rhabdomyosarcoma; Recurrent Childhood Soft Tissue Sarcoma; Recurrent Childhood Visual Pathway and Hypothalamic Glioma; Recurrent Colon Cancer; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Nasopharyngeal Cancer; Recurrent Neuroblastoma; Recurrent Osteosarcoma; Recurrent Rectal Cancer; Recurrent Renal Cell Cancer

Chick stem cells: Current progress and future prospects

PubMed Central

Intarapat, Sittipon; Stern, Claudio D.

2013-01-01

Chick embryonic stem cells (cESCs) can be derived from cells obtained from stage X embryos (blastoderm stage); these have the ability to contribute to all somatic lineages in chimaeras, but not to the germ line. However, lines of stem cells that are able to contribute to the germ line can be established from chick primordial germ cells (cPGCs) and embryonic germ cells (cEGCs). This review provides information on avian stem cells, emphasizing different sources of cells and current methods for derivation and culture of pluripotent cells from chick embryos. We also review technologies for isolation and derivation of chicken germ cells and the production of transgenic birds. PMID:24103496

Germ plasm localisation of the HELICc of Vasa in Drosophila: analysis of domain sufficiency and amino acids critical for localisation

NASA Astrophysics Data System (ADS)

Wang, Szu-Chieh; Hsu, Hao-Jen; Lin, Gee-Way; Wang, Ting-Fang; Chang, Chun-Che; Lin, Ming-Der

2015-09-01

Formation of the germ plasm drives germline specification in Drosophila and some other insects such as aphids. Identification of the DEAD-box protein Vasa (Vas) as a conserved germline marker in flies and aphids suggests that they share common components for assembling the germ plasm. However, to which extent the assembly order is conserved and the correlation between functions and sequences of Vas remain unclear. Ectopic expression of the pea aphid Vas (ApVas1) in Drosophila did not drive its localisation to the germ plasm, but ApVas1 with a replaced C-terminal domain (HELICc) of Drosophila Vas (DmVas) became germ-plasm restricted. We found that HELICc itself, through the interaction with Oskar (Osk), was sufficient for germ-plasm localisation. Similarly, HELICc of the grasshopper Vas could be recruited to the germ plasm in Drosophila. Nonetheless, germ-plasm localisation was not seen in the Drosophila oocytes expressing HELICcs of Vas orthologues from aphids, crickets, and mice. We further identified that glutamine (Gln) 527 within HELICc of DmVas was critical for localisation, and its corresponding residue could also be detected in grasshopper Vas yet missing in the other three species. This suggests that Gln527 is a direct target of Osk or critical to the maintenance of HELICc conformation.

Environmentally Induced Transgenerational Epigenetic Reprogramming of Primordial Germ Cells and the Subsequent Germ Line

PubMed Central

Skinner, Michael K.; Haque, Carlos Guerrero-Bosagna M.; Nilsson, Eric; Bhandari, Ramji; McCarrey, John R.

2013-01-01

A number of environmental factors (e.g. toxicants) have been shown to promote the epigenetic transgenerational inheritance of disease and phenotypic variation. Transgenerational inheritance requires the germline transmission of altered epigenetic information between generations in the absence of direct environmental exposures. The primary periods for epigenetic programming of the germ line are those associated with primordial germ cell development and subsequent fetal germline development. The current study examined the actions of an agricultural fungicide vinclozolin on gestating female (F0 generation) progeny in regards to the primordial germ cell (PGC) epigenetic reprogramming of the F3 generation (i.e. great-grandchildren). The F3 generation germline transcriptome and epigenome (DNA methylation) were altered transgenerationally. Interestingly, disruptions in DNA methylation patterns and altered transcriptomes were distinct between germ cells at the onset of gonadal sex determination at embryonic day 13 (E13) and after cord formation in the testis at embryonic day 16 (E16). A larger number of DNA methylation abnormalities (epimutations) and transcriptional alterations were observed in the E13 germ cells than in the E16 germ cells. These observations indicate that altered transgenerational epigenetic reprogramming and function of the male germline is a component of vinclozolin induced epigenetic transgenerational inheritance of disease. Insights into the molecular control of germline transmitted epigenetic inheritance are provided. PMID:23869203

Generation of male differentiated germ cells from various types of stem cells.

PubMed

Hou, Jingmei; Yang, Shi; Yang, Hao; Liu, Yang; Liu, Yun; Hai, Yanan; Chen, Zheng; Guo, Ying; Gong, Yuehua; Gao, Wei-Qiang; Li, Zheng; He, Zuping

2014-06-01

Infertility is a major and largely incurable disease caused by disruption and loss of germ cells. It affects 10-15% of couples, and male factor accounts for half of the cases. To obtain human male germ cells 'especially functional spermatids' is essential for treating male infertility. Currently, much progress has been made on generating male germ cells, including spermatogonia, spermatocytes, and spermatids, from various types of stem cells. These germ cells can also be used in investigation of the pathology of male infertility. In this review, we focused on advances on obtaining male differentiated germ cells from different kinds of stem cells, with an emphasis on the embryonic stem (ES) cells, the induced pluripotent stem (iPS) cells, and spermatogonial stem cells (SSCs). We illustrated the generation of male differentiated germ cells from ES cells, iPS cells and SSCs, and we summarized the phenotype for these stem cells, spermatocytes and spermatids. Moreover, we address the differentiation potentials of ES cells, iPS cells and SSCs. We also highlight the advantages, disadvantages and concerns on derivation of the differentiated male germ cells from several types of stem cells. The ability of generating mature and functional male gametes from stem cells could enable us to understand the precise etiology of male infertility and offer an invaluable source of autologous male gametes for treating male infertility of azoospermia patients. © 2014 Society for Reproduction and Fertility.

Three-Step Method for Proliferation and Differentiation of Human Embryonic Stem Cell (hESC)-Derived Male Germ Cells

PubMed Central

Lim, Jung Jin; Shim, Myung Sun; Lee, Jeoung Eun; Lee, Dong Ryul

2014-01-01

The low efficiency of differentiation into male germ cell (GC)-like cells and haploid germ cells from human embryonic stem cells (hESCs) reflects the culture method employed in the two-dimensional (2D)-microenvironment. In this study, we applied a three-step media and calcium alginate-based 3D-culture system for enhancing the differentiation of hESCs into male germ stem cell (GSC)-like cells and haploid germ cells. In the first step, embryoid bodies (EBs) were derived from hESCs cultured in EB medium for 3 days and re-cultured for 4 additional days in EB medium with BMP4 and RA to specify GSC-like cells. In the second step, the resultant cells were cultured in GC-proliferation medium for 7 days. The GSC-like cells were then propagated after selection using GFR-α1 and were further cultured in GC-proliferation medium for 3 weeks. In the final step, a 3D-co-culture system using calcium alginate encapsulation and testicular somatic cells was applied to induce differentiation into haploid germ cells, and a culture containing approximately 3% male haploid germ cells was obtained after 2 weeks of culture. These results demonstrated that this culture system could be used to efficiently induce GSC-like cells in an EB population and to promote the differentiation of ESCs into haploid male germ cells. PMID:24690677

Regulatory mechanism of protein metabolic pathway during the differentiation process of chicken male germ cell.

PubMed

Li, Dong; Zuo, Qisheng; Lian, Chao; Zhang, Lei; Shi, Qingqing; Zhang, Zhentao; Wang, Yingjie; Ahmed, Mahmoud F; Tang, Beibei; Xiao, Tianrong; Zhang, Yani; Li, Bichun

2015-08-01

We explored the regulatory mechanism of protein metabolism during the differentiation process of chicken male germ cells and provide a basis for improving the induction system of embryonic stem cell differentiation to male germ cells in vitro. We sequenced the transcriptome of embryonic stem cells, primordial germ cells, and spermatogonial stem cells with RNA sequencing (RNA-Seq), bioinformatics analysis methods, and detection of the key genes by quantitative reverse transcription PCR (qRT-PCR). Finally, we found 16 amino acid metabolic pathways enriched in the biological metabolism during the differentiation process of embryonic stem cells to primordial germ cells and 15 amino acid metabolic pathways enriched in the differentiation stage of primordial germ cells to spermatogonial stem cells. We found three pathways, arginine-proline metabolic pathway, tyrosine metabolic pathway, and tryptophan metabolic pathway, significantly enriched in the whole differentiation process of embryonic stem cells to spermatogonial stem cells. Moreover, for these three pathways, we screened key genes such as NOS2, ADC, FAH, and IDO. qRT-PCR results showed that the expression trend of these genes were the same to RNA-Seq. Our findings showed that the three pathways and these key genes play an important role in the differentiation process of embryonic stem cells to male germ cells. These results provide basic information for improving the induction system of embryonic stem cell differentiation to male germ cells in vitro.

X-inactivation and X-reactivation: epigenetic hallmarks of mammalian reproduction and pluripotent stem cells.

PubMed

Payer, Bernhard; Lee, Jeannie T; Namekawa, Satoshi H

2011-08-01

X-chromosome inactivation is an epigenetic hallmark of mammalian development. Chromosome-wide regulation of the X-chromosome is essential in embryonic and germ cell development. In the male germline, the X-chromosome goes through meiotic sex chromosome inactivation, and the chromosome-wide silencing is maintained from meiosis into spermatids before the transmission to female embryos. In early female mouse embryos, X-inactivation is imprinted to occur on the paternal X-chromosome, representing the epigenetic programs acquired in both parental germlines. Recent advances revealed that the inactive X-chromosome in both females and males can be dissected into two elements: repeat elements versus unique coding genes. The inactive paternal X in female preimplantation embryos is reactivated in the inner cell mass of blastocysts in order to subsequently allow the random form of X-inactivation in the female embryo, by which both Xs have an equal chance of being inactivated. X-chromosome reactivation is regulated by pluripotency factors and also occurs in early female germ cells and in pluripotent stem cells, where X-reactivation is a stringent marker of naive ground state pluripotency. Here we summarize recent progress in the study of X-inactivation and X-reactivation during mammalian reproduction and development as well as in pluripotent stem cells.

Dasatinib, Ifosfamide, Carboplatin, and Etoposide in Treating Young Patients With Metastatic or Recurrent Malignant Solid Tumors

ClinicalTrials.gov

2018-02-09

Brain and Central Nervous System Tumors; Childhood Germ Cell Tumor; Extragonadal Germ Cell Tumor; Kidney Cancer; Liver Cancer; Lymphoma; Neuroblastoma; Ovarian Cancer; Sarcoma; Testicular Germ Cell Tumor; Unspecified Childhood Solid Tumor, Protocol Specific

Identification of tissues and patterning events required for distinct steps in early migration of zebrafish primordial germ cells.

PubMed

Weidinger, G; Wolke, U; Köprunner, M; Klinger, M; Raz, E

1999-12-01

In many organisms, the primordial germ cells have to migrate from the position where they are specified towards the developing gonad where they generate gametes. Extensive studies of the migration of primordial germ cells in Drosophila, mouse, chick and Xenopus have identified somatic tissues important for this process and demonstrated a role for specific molecules in directing the cells towards their target. In zebrafish, a unique situation is found in that the primordial germ cells, as marked by expression of vasa mRNA, are specified in random positions relative to the future embryonic axis. Hence, the migrating cells have to navigate towards their destination from various starting positions that differ among individual embryos. Here, we present a detailed description of the migration of the primordial germ cells during the first 24 hours of wild-type zebrafish embryonic development. We define six distinct steps of migration bringing the primordial germ cells from their random positions before gastrulation to form two cell clusters on either side of the midline by the end of the first day of development. To obtain information on the origin of the positional cues provided to the germ cells by somatic tissues during their migration, we analyzed the migration pattern in mutants, including spadetail, swirl, chordino, floating head, cloche, knypek and no isthmus. In mutants with defects in axial structures, paraxial mesoderm or dorsoventral patterning, we find that certain steps of the migration process are specifically affected. We show that the paraxial mesoderm is important for providing proper anteroposterior information to the migrating primordial germ cells and that these cells can respond to changes in the global dorsoventral coordinates. In certain mutants, we observe accumulation of ectopic cells in different regions of the embryo. These ectopic cells can retain both morphological and molecular characteristics of primordial germ cells, suggesting that, in zebrafish at the early stages tested, the vasa-expressing cells are committed to the germ cell lineage.

Development, differentiation and manipulation of chicken germ cells.

PubMed

Nakamura, Yoshiaki; Kagami, Hiroshi; Tagami, Takahiro

2013-01-01

Germ cells are the only cell type capable of transmitting genetic information to the next generation. During development, they are set aside from all somatic cells of the embryo. In many species, germ cells form at the fringe of the embryo proper and then traverse through several developing somatic tissues on their migration to the emerging gonads. Primordial germ cells (PGCs) are the only cells in developing embryos with the potential to transmit genetic information to the next generation. Unlike other species, in avian embryos, PGCs use blood circulation for transport to the future gonadal region. This unique accessibility of avian PGCs during early development provides an opportunity to collect and transplant PGCs. The recent development of methods for production of germline chimeras by transfer of PGCs, and long-term cultivation methods of chicken PGCs without losing their germline transmission ability have provided important breakthroughs for the preservation of germplasm , for the production of transgenic birds and study the germ cell system. This review will describe the development, migration, differentiation and manipulation of germ cells, and discuss the prospects that germ cell technologies offer for agriculture, biotechnology and academic research. © 2013 The Authors Development, Growth & Differentiation © 2013 Japanese Society of Developmental Biologists.

Germ stem cells are active in postnatal mouse ovary under physiological conditions

PubMed Central

Guo, Kun; Li, Chao-hui; Wang, Xin-yi; He, Da-jian; Zheng, Ping

2016-01-01

STUDY HYPOTHESIS Are active ovarian germ stem cells present in postnatal mouse ovaries under physiological conditions? STUDY FINDING Active ovarian germ stem cells exist and function in adult mouse ovaries under physiological conditions. WHAT IS KNOWN ALREADY In vitro studies suggested the existence of germ stem cells in postnatal ovaries of mouse, pig and human. However, in vivo studies provided evidence against the existence of active germ stem cells in postnatal mouse ovaries. Thus, it remains controversial whether such germ stem cells really exist and function in vivo in postnatal mammalian ovaries. STUDY DESIGN, SAMPLES/MATERIALS, METHODS Octamer-binding transcription factor 4 (Oct4)-MerCreMer transgenic mice were crossed with R26R-enhanced yellow fluorescent protein (EYFP) mice to establish a tamoxifen-inducible tracing system so that Oct4-expressing potential ovarian germ stem cells in young adult mice (5–6 weeks old) can be labeled with EYFP. The germ cell activities of DNA replication, mitotic division, entry into meiosis and progression to primordial follicle stage were investigated by means of immunofluorescent staining of ovarian tissues collected at different time points post-tamoxifen injection (1 day, 3 days, 2 months and 4 months). Meiosis entry and primordial follicle formation were also measured by EYFP-labeled single-cell RT–PCR. Germ cell proliferation and mitotic division were examined through 5-bromodeoxyuridine triphosphate incorporation assay. At each time point, ovaries from two to three animals were used for each set of experiment. MAIN RESULTS AND THE ROLE OF CHANCE By labeling the Oct4-expressing small germ cells and tracing their fates for up to 4 months, we observed persistent meiosis entry and primordial follicle replenishment. Furthermore, we captured the transient processes of mitotic DNA replication as well as mitotic division of the marked germ cells at various time periods after tracing. These lines of evidence unambiguously support the presence of active germ stem cells in postnatal ovaries and their function in replenishing primordial follicle pool under physiological conditions. Moreover, we pointed out that Oct4+ deleted in azoospermia-like (Dazl)− but not Oct4+Dazl+ or Oct4+ DEAD (Asp–Glu–Ala–Asp) Box Polypeptide 4 (Ddx4)+ cells contain a population of germ stem cells in mouse ovary. LIMITATIONS, REASONS FOR CAUTION This study was conducted in mice. Whether or not the results are applicable to human remain unclear. The future work should aim at identifying the specific ovarian germ stem cell marker and evaluating the significance of these stem cells to normal ovarian function. WIDER IMPLICATIONS OF THE FINDINGS Clarifying the existence of active germ stem cells and their functional significance in postnatal mammalian ovaries could provide new insights in understanding the mechanism of ovarian aging and failure. LARGE SCALE DATA Not applicable. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by the National Key Basic Research Program of China (grant number 2012CBA01300) and the National Natural Science Foundation of China to P.Z. (31571484). No competing interests are reported. PMID:26916381

Study of Small Ligands Which Bind Specifically to Breast Cancer Cells

DTIC Science & Technology

1997-09-01

Sepharose conjugated to three different lectins: ConA, wheat germ and lentil,. Each lectin bound many proteins in both the ECD-AP sup and the control 3T3 sup...control Lanes 13-14: Wheat germ ECD-AP Lanes 15-16: Wheat germ 3T3 control Odd lanes were eluted with a low sugar concentration; even lanes were...ECD-AP post incubation with lentil-Sepharose Lane 6: Protein remaining in pp ECD-AP post incubation with wheat germ -Sepharose Lane 8: Protein

Forestry-related pathways for the movement of exotic plant pests into and within the greater Caribbean region

Treesearch

Leslie Newton; Heike Meissner; Andrea. Lemay

2011-01-01

Forests of the Greater Caribbean Region (GCR) are important ecologically and economically. These unique ecosystems are under increasing pressure from exotic pests, which may cause extensive environmental damage and cost billions of dollars in control programs, lost production, and forest restoration.

An investigation into the role of metastable states on excited populations of weakly ionized argon plasmas, with applications for optical diagnostics

NASA Astrophysics Data System (ADS)

Arnold, Nicholas; Loch, Stuart; Ballance, Connor; Thomas, Ed

2017-10-01

Low temperature plasmas (Te < 10 eV) are ubiquitous in the medical, industrial, basic, and dusty plasma communities, and offer an opportunity for researchers to gain a better understanding of atomic processes in plasmas. Here, we report on a new atomic dataset for neutral and low charge states of argon, from which rate coefficients and cross-sections for the electron-impact excitation of neutral argon are determined. We benchmark by comparing with electron impact excitation cross-sections available in the literature, with very good agreement. We have used the Atomic Data and Analysis Structure (ADAS) code suite to calculate a level-resolved, generalized collisional-radiative (GCR) model for line emission in low temperature argon plasmas. By combining our theoretical model with experimental electron temperature, density, and spectral measurements from the Auburn Linear eXperiment for Instability Studies (ALEXIS), we have developed diagnostic techniques to measure metastable fraction, electron temperature, and electron density. In the future we hope to refine our methods, and extend our model to plasmas other than ALEXIS. Supported by the U.S. Department of Energy. Grant Number: DE-FG02-00ER54476.

Radiation transport simulation of the Martian GCR surface flux and dose estimation using spherical geometry in PHITS compared to MSL-RAD measurements

NASA Astrophysics Data System (ADS)

Flores-McLaughlin, John

2017-08-01

Planetary bodies and spacecraft are predominantly exposed to isotropic radiation environments that are subject to transport and interaction in various material compositions and geometries. Specifically, the Martian surface radiation environment is composed of galactic cosmic radiation, secondary particles produced by their interaction with the Martian atmosphere, albedo particles from the Martian regolith and occasional solar particle events. Despite this complex physical environment with potentially significant locational and geometric dependencies, computational resources often limit radiation environment calculations to a one-dimensional or slab geometry specification. To better account for Martian geometry, spherical volumes with respective Martian material densities are adopted in this model. This physical description is modeled with the PHITS radiation transport code and compared to a portion of measurements from the Radiation Assessment Detector of the Mars Science Laboratory. Particle spectra measured between 15 November 2015 and 15 January 2016 and PHITS model results calculated for this time period are compared. Results indicate good agreement between simulated dose rates, proton, neutron and gamma spectra. This work was originally presented at the 1st Mars Space Radiation Modeling Workshop held in 2016 in Boulder, CO.

Radiation transport simulation of the Martian GCR surface flux and dose estimation using spherical geometry in PHITS compared to MSL-RAD measurements.

PubMed

Flores-McLaughlin, John

2017-08-01

Planetary bodies and spacecraft are predominantly exposed to isotropic radiation environments that are subject to transport and interaction in various material compositions and geometries. Specifically, the Martian surface radiation environment is composed of galactic cosmic radiation, secondary particles produced by their interaction with the Martian atmosphere, albedo particles from the Martian regolith and occasional solar particle events. Despite this complex physical environment with potentially significant locational and geometric dependencies, computational resources often limit radiation environment calculations to a one-dimensional or slab geometry specification. To better account for Martian geometry, spherical volumes with respective Martian material densities are adopted in this model. This physical description is modeled with the PHITS radiation transport code and compared to a portion of measurements from the Radiation Assessment Detector of the Mars Science Laboratory. Particle spectra measured between 15 November 2015 and 15 January 2016 and PHITS model results calculated for this time period are compared. Results indicate good agreement between simulated dose rates, proton, neutron and gamma spectra. This work was originally presented at the 1st Mars Space Radiation Modeling Workshop held in 2016 in Boulder, CO. Copyright © 2017. Published by Elsevier Ltd.

Solar particle events observed at Mars: dosimetry measurements and model calculations

NASA Astrophysics Data System (ADS)

Cleghorn, T.; Saganti, P.; Zeitlin, C.; Cucinotta, F.

The first solar particle events from a Martian orbit are observed with the MARIE (Martian Radiation Environment Experiment) on the 2001 Mars Odyssey space -craft that is currently in orbit and collecting the mapping data of the red planet. These solar particle events observed at Mars during March and April 2002, are correlated with the GOES-8 and ACE satellite data from the same time period at Earth orbits. Dosimetry measurements for the Mars orbit from the period of March 13t h through April 29t h . Particle count rate and the corresponding dose rate enhancements were observed on March 16t h through 20t h and on April 22n d corresponding to solar particle events that were observed at Earth orbit on March 16t h through 21s t and beginning on April 21s t respectively. The model calculations with the HZETRN (High Z=atomic number and high Energy Transport) code estimated the background GCR (Galactic Cosmic Rays) dose rates. The dose rates observed by the MARIE instrument are within 10% of the model calculations. Dosimetry measurements and model calculation will be presented.

Psychosexual Intervention in Patients With Stage I-III Gynecologic or Breast Cancer

ClinicalTrials.gov

2018-05-25

Ovarian Sarcoma; Ovarian Stromal Cancer; Stage I Uterine Sarcoma; Stage I Vaginal Cancer; Stage I Vulvar Cancer; Stage IA Cervical Cancer; Stage IA Endometrial Carcinoma; Stage IA Fallopian Tube Cancer; Stage IA Ovarian Epithelial Cancer; Stage IA Ovarian Germ Cell Tumor; Stage IA Primary Peritoneal Cavity Cancer; Stage IB Cervical Cancer; Stage IB Endometrial Carcinoma; Stage IB Fallopian Tube Cancer; Stage IB Ovarian Epithelial Cancer; Stage IB Ovarian Germ Cell Tumor; Stage IB Primary Peritoneal Cavity Cancer; Stage IC Fallopian Tube Cancer; Stage IC Ovarian Epithelial Cancer; Stage IC Ovarian Germ Cell Tumor; Stage IC Primary Peritoneal Cavity Cancer; Stage II Endometrial Carcinoma; Stage II Gestational Trophoblastic Tumor; Stage II Uterine Sarcoma; Stage II Vaginal Cancer; Stage II Vulvar Cancer; Stage IIA Cervical Cancer; Stage IIA Fallopian Tube Cancer; Stage IIA Ovarian Epithelial Cancer; Stage IIA Ovarian Germ Cell Tumor; Stage IIA Primary Peritoneal Cavity Cancer; Stage IIB Cervical Cancer; Stage IIB Fallopian Tube Cancer; Stage IIB Ovarian Epithelial Cancer; Stage IIB Ovarian Germ Cell Tumor; Stage IIB Primary Peritoneal Cavity Cancer; Stage IIC Fallopian Tube Cancer; Stage IIC Ovarian Epithelial Cancer; Stage IIC Ovarian Germ Cell Tumor; Stage IIC Primary Peritoneal Cavity Cancer; Stage III Gestational Trophoblastic Tumor; Stage III Uterine Sarcoma; Stage III Vaginal Cancer; Stage III Vulvar Cancer; Stage IIIA Cervical Cancer; Stage IIIA Endometrial Carcinoma; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Epithelial Cancer; Stage IIIA Ovarian Germ Cell Tumor; Stage IIIA Primary Peritoneal Cavity Cancer; Stage IIIB Cervical Cancer; Stage IIIB Endometrial Carcinoma; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Epithelial Cancer; Stage IIIB Ovarian Germ Cell Tumor; Stage IIIB Primary Peritoneal Cavity Cancer; Stage IIIC Endometrial Carcinoma; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Epithelial Cancer; Stage IIIC Ovarian Germ Cell Tumor; Stage IIIC Primary Peritoneal Cavity Cancer; Breast Cancer

Distinct and Cooperative Roles of amh and dmrt1 in Self-Renewal and Differentiation of Male Germ Cells in Zebrafish.

PubMed

Lin, Qiaohong; Mei, Jie; Li, Zhi; Zhang, Xuemei; Zhou, Li; Gui, Jian-Fang

2017-11-01

Spermatogenesis is a fundamental process in male reproductive biology and depends on precise balance between self-renewal and differentiation of male germ cells. However, the regulative factors for controlling the balance are poorly understood. In this study, we examined the roles of amh and dmrt1 in male germ cell development by generating their mutants with Crispr/Cas9 technology in zebrafish. Amh mutant zebrafish displayed a female-biased sex ratio, and both male and female amh mutants developed hypertrophic gonads due to uncontrolled proliferation and impaired differentiation of germ cells. A large number of proliferating spermatogonium-like cells were observed within testicular lobules of the amh -mutated testes, and they were demonstrated to be both Vasa- and PH3-positive. Moreover, the average number of Sycp3- and Vasa-positive cells in the amh mutants was significantly lower than in wild-type testes, suggesting a severely impaired differentiation of male germ cells. Conversely, all the dmrt1 -mutated testes displayed severe testicular developmental defects and gradual loss of all Vasa-positive germ cells by inhibiting their self-renewal and inducing apoptosis. In addition, several germ cell and Sertoli cell marker genes were significantly downregulated, whereas a prominent increase of Insl3-positive Leydig cells was revealed by immunohistochemical analysis in the disorganized dmrt1 -mutated testes. Our data suggest that amh might act as a guardian to control the balance between proliferation and differentiation of male germ cells, whereas dmrt1 might be required for the maintenance, self-renewal, and differentiation of male germ cells. Significantly, this study unravels novel functions of amh gene in fish. Copyright © 2017 by the Genetics Society of America.

Signaling through the TGF Beta-Activin Receptors ALK4/5/7 Regulates Testis Formation and Male Germ Cell Development

PubMed Central

Stringer, Jessica M.; van den Bergen, Jocelyn A.; Wilhelm, Dagmar; Sinclair, Andrew H.; Western, Patrick S.

2013-01-01

The developing testis provides an environment that nurtures germ cell development, ultimately ensuring spermatogenesis and fertility. Impacts on this environment are considered to underlie aberrant germ cell development and formation of germ cell tumour precursors. The signaling events involved in testis formation and male fetal germ cell development remain largely unknown. Analysis of knockout mice lacking single Tgfβ family members has indicated that Tgfβ's are not required for sex determination. However, due to functional redundancy, it is possible that additional functions for these ligands in gonad development remain to be discovered. Using FACS purified gonadal cells, in this study we show that the genes encoding Activin's, TGFβ's, Nodal and their respective receptors, are expressed in sex and cell type specific patterns suggesting particular roles in testis and germ cell development. Inhibition of signaling through the receptors ALK4, ALK5 and ALK7, and ALK5 alone, demonstrated that TGFβ signaling is required for testis cord formation during the critical testis-determining period. We also show that signaling through the Activin/NODAL receptors, ALK4 and ALK7 is required for promoting differentiation of male germ cells and their entry into mitotic arrest. Finally, our data demonstrate that Nodal is specifically expressed in male germ cells and expression of the key pluripotency gene, Nanog was significantly reduced when signaling through ALK4/5/7 was blocked. Our strategy of inhibiting multiple Activin/NODAL/TGFβ receptors reduces the functional redundancy between these signaling pathways, thereby revealing new and essential roles for TGFβ and Activin signaling during testis formation and male germ cell development. PMID:23342175

A Novel Dynamic Expression of vasa in Male Germ Cells during Spermatogenesis in the Chinese Soft-Shell Turtle (Pelidiscus sinensis).

PubMed

Li, Wei; Zhang, Piaoyi; Wu, Xuling; Zhu, Xinping; Xu, Hongyan

2017-05-01

vasa gene encodes a highly conserved DEAD-box RNA helicase, required for germ cell development across animal kingdom. Vasa mutations cause male infertility in mammals. It has been widely used as a biomarker for studying animal fertility or manipulating germ cells in organisms. However, in reptilians, the functions of vasa gene involved in germ cell differentiation are largely unclear; this hampers the development of biological techniques and the improvement of the productivity in these species. Here a vasa cDNA was isolated in Chinese soft-shell turtle and it predicts a protein of 691 amino acid residues, which is 72%, 69%, 58%, 59%, and 54-56% identical to its homolog from mouse, platypus, frog, chicken, and fish, respectively, and named as PsVasa. The Psvasa mRNA was detected exclusively in the gonads of both sexes by RT-PCR. Chromogenic RNA in situ hybridization revealed that the Psvasa mRNA was restricted to germ cells in the testis: The psvasa mRNA is undetectable in resting spermatogonia, appears in proliferating spermatogonia, and becomes abundant in spermatocytes and detectable in spermatozoa. Immunofluorescence staining demonstrated that the PsVasa in the testis is also restricted to the germ cells, rich in spermatocytes and elongated spermatids but hardly detectable in spermatogonia and spermatozoa. Taken together, Psvasa is potentially a reliable germ cell marker in the Chinese soft-shell turtle; its RNA expression could distinguish the different spermatogenic stages of germ cells. These findings shed new insights into understanding the evolutionary conservations and divergences of vasa gene's functions in male germ cell differentiation in metazoans. © 2017 Wiley Periodicals, Inc.

Is Tobacco Smoke a Germ-Cell Mutagen?

EPA Science Inventory

Although no international organization exists to declare whether an agent is a germ-cell mutagen, tobacco smoke may be a human germ-cell mutagen. In the mouse, tobacco smoke induces a significant increase in the mutation frequency at an expanded simple tandem repeat (ESTR) locus....

The Crystal Structure of the Drosophila Germline Inducer Oskar Identifies Two Domains with Distinct Vasa Helicase- and RNA-Binding Activities.

PubMed

Jeske, Mandy; Bordi, Matteo; Glatt, Sebastian; Müller, Sandra; Rybin, Vladimir; Müller, Christoph W; Ephrussi, Anne

2015-07-28

In many animals, the germ plasm segregates germline from soma during early development. Oskar protein is known for its ability to induce germ plasm formation and germ cells in Drosophila. However, the molecular basis of germ plasm formation remains unclear. Here, we show that Oskar is an RNA-binding protein in vivo, crosslinking to nanos, polar granule component, and germ cell-less mRNAs, each of which has a role in germline formation. Furthermore, we present high-resolution crystal structures of the two Oskar domains. RNA-binding maps in vitro to the C-terminal domain, which shows structural similarity to SGNH hydrolases. The highly conserved N-terminal LOTUS domain forms dimers and mediates Oskar interaction with the germline-specific RNA helicase Vasa in vitro. Our findings suggest a dual function of Oskar in RNA and Vasa binding, providing molecular clues to its germ plasm function. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Aspergillus flavus Infection and Aflatoxin Production in Corn: Influence of Trace Elements

PubMed Central

Lillehoj, E. B.; Garcia, W. J.; Lambrow, M.

1974-01-01

Distribution of trace element levels in corn germ fractions from kernels naturally infected with Aspergillus flavus and from kernels free of the fungus demonstrated an association between the presence of A. flavus and higher levels of metals. A. flavus production of aflatoxin on various autoclaved corn media showed that ground, whole corn was an excellent substrate; similar high levels of toxin were observed on full-fat corn germ but endosperm and defatted corn germ supported reduced yields. The influence of trace elements and their availability in defatted corn germ to A. flavus-mediated aflatoxin biosynthesis were measured. Enrichment of the substrate with 5 to 10 μg of manganese, copper, cadmium, or chromium per g of germ increased toxin yields. Addition of lead or zinc (50 to 250 μg/g) also enhanced toxin accumulation. Aflatoxin elaboration was reduced by the addition of 25 μg of cadmium per g or 500 μg of copper per g of germ. PMID:4216287

Physicochemical properties of nixtamalized corn flours with and without germ.

PubMed

Vega Rojas, Lineth J; Rojas Molina, Isela; Gutiérrez Cortez, Elsa; Rincón Londoño, Natalia; Acosta Osorio, Andrés A; Del Real López, Alicia; Rodríguez García, Mario E

2017-04-01

This research studied the influence of the germ components on the physicochemical properties of cooked corn and nixtamalized corn flours as a function of the calcium hydroxide content (from 0 to 2.1 w/w) and steeping time (between 0 and 9h). A linear relationship was found between calcium content in germ and steeping time used during nixtamalization process. X-ray diffraction analysis showed that calcium carbonate is formed into the germ structure to 2.1 w/w of calcium hydroxide and 9h steeping time. The presence of the germ improves the development of peak viscosity in flours, and it is related to the increases in calcium concentration in germ and the formation of amylose-lipid complexes. No significant changes were observed in palmitic, stearic, oleic and linoleic acids of corn oil. The levels of further corn oil deterioration were 2.1 w/w of calcium hydroxide concentration and 9h of steeping time. Copyright © 2016 Elsevier Ltd. All rights reserved.

Retroperitoneal dedifferentiated liposarcoma lacking MDM2 amplification in a patient with a germ line CHEK2 mutation.

PubMed

Sadri, Navid; Surrey, Lea F; Fraker, Douglas L; Zhang, Paul J

2014-04-01

Germ line mutations in genes that encode proteins involved in the DNA damage response predispose patients to a variety of tumors. Checkpoint kinase 2, encoded by the CHEK2 gene, is important in transducing the DNA damage response. Germ line CHEK2 mutations are seen in a subset of patients with a familial breast cancer and sarcoma phenotype. We report a case of retroperitoneal dedifferentiated liposarcoma in a 61-year-old female with germ line CHEK2 mutation. MDM2 gene amplification normally present and used to aid in the diagnosis of retroperitoneal dedifferentiated liposarcoma was absent in this case. Lack of MDM2 overexpression has similarly been reported in liposarcomas arising in patients with germ line TP53 mutations. We propose this case may highlight a nonamplified MDM2 phenotype in well- and dedifferentiated liposarcomas arising in patients with germ line mutations of genes involved in p53-associated DNA damage response pathways.

Female mice lack adult germ-line stem cells but sustain oogenesis using stable primordial follicles.

PubMed

Lei, Lei; Spradling, Allan C

2013-05-21

Whether or not mammalian females generate new oocytes during adulthood from germ-line stem cells to sustain the ovarian follicle pool has recently generated controversy. We used a sensitive lineage-labeling system to determine whether stem cells are needed in female adult mice to compensate for follicular losses and to directly identify active germ-line stem cells. Primordial follicles generated during fetal life are highly stable, with a half-life during adulthood of 10 mo, and thus are sufficient to sustain adult oogenesis without a source of renewal. Moreover, in normal mice or following germ-cell depletion with Busulfan, only stable, single oocytes are lineage-labeled, rather than cell clusters indicative of new oocyte formation. Even one germ-line stem cell division per 2 wk would have been detected by our method, based on the kinetics of fetal follicle formation. Thus, adult female mice neither require nor contain active germ-line stem cells or produce new oocytes in vivo.