ACO-Initialized Wavelet Neural Network for Vibration Fault Diagnosis of Hydroturbine Generating Unit

Directory of Open Access Journals (Sweden)

Zhihuai Xiao

2015-01-01

Full Text Available Considering the drawbacks of traditional wavelet neural network, such as low convergence speed and high sensitivity to initial parameters, an ant colony optimization- (ACO- initialized wavelet neural network is proposed in this paper for vibration fault diagnosis of a hydroturbine generating unit. In this method, parameters of the wavelet neural network are initialized by the ACO algorithm, and then the wavelet neural network is trained by the gradient descent algorithm. Amplitudes of the frequency components of the hydroturbine generating unit vibration signals are used as feature vectors for wavelet neural network training to realize mapping relationship from vibration features to fault types. A real vibration fault diagnosis case result of a hydroturbine generating unit shows that the proposed method has faster convergence speed and stronger generalization ability than the traditional wavelet neural network and ACO wavelet neural network. Thus it can provide an effective solution for online vibration fault diagnosis of a hydroturbine generating unit.

Mesenchymal stem cells cancel azoxymethane-induced tumor initiation.

Science.gov (United States)

Nasuno, Masanao; Arimura, Yoshiaki; Nagaishi, Kanna; Isshiki, Hiroyuki; Onodera, Kei; Nakagaki, Suguru; Watanabe, Shuhei; Idogawa, Masashi; Yamashita, Kentaro; Naishiro, Yasuyoshi; Adachi, Yasushi; Suzuki, Hiromu; Fujimiya, Mineko; Imai, Kohzoh; Shinomura, Yasuhisa

2014-04-01

The role of mesenchymal stem cells (MSCs) in tumorigenesis remains controversial. Therefore, our goal was to determine whether exogenous MSCs possess intrinsic antineoplastic or proneoplastic properties in azoxymethane (AOM)-induced carcinogenesis. Three in vivo models were studied: an AOM/dextran sulfate sodium colitis-associated carcinoma model, an aberrant crypt foci model, and a model to assess the acute apoptotic response of a genotoxic carcinogen (AARGC). We also performed in vitro coculture experiments. As a result, we found that MSCs partially canceled AOM-induced tumor initiation but not tumor promotion. Moreover, MSCs inhibited the AARGC in colonic epithelial cells because of the removal of O(6)-methylguanine (O(6) MeG) adducts through O(6) MeG-DNA methyltransferase activation. Furthermore, MSCs broadly affected the cell-cycle machinery, potentially leading to G1 arrest in vivo. Coculture of IEC-6 rat intestinal cells with MSCs not only arrested the cell cycle at the G1 phase, but also induced apoptosis. The anti-carcinogenetic properties of MSCs in vitro required transforming growth factor (TGF)-β signaling because such properties were completely abrogated by absorption of TGF-β under indirect coculture conditions. MSCs inhibited AOM-induced tumor initiation by preventing the initiating cells from sustaining DNA insults and subsequently inducing G1 arrest in the initiated cells that escaped from the AARGC. Furthermore, tumor initiation perturbed by MSCs might potentially dysregulate WNT and TGF-β-Smad signaling pathways in subsequent tumorigenesis. Obtaining a better understanding of MSC functions in colon carcinogenesis is essential before commencing the broader clinical application of promising MSC-based therapies for cancer-prone patients with inflammatory bowel disease. © AlphaMed Press.

United States policy initiatives in promoting the RERTR program

International Nuclear Information System (INIS)

Huizenga, David G.

1996-01-01

The Reduced Enrichment for Research and Test Reactors (RERTR) program has been successful in furthering efforts to reduce and eventually eliminate highly enriched uranium (HEU) from international commerce. Three key policy initiatives are underway to further promote the RERTR program. The first initiative is implementation of a new nuclear weapons nonproliferation policy concerning foreign research reactor spent nuclear fuel. Under this policy, the United States will accept over the next 13 years research reactor spent fuel from 41 countries that have converted or plan to convert to use LEU fuels. The second initiative is to pursue cooperative efforts to expand the RERTR program to new regions of the globe, including Russia and China. The third initiative is to restart the advanced LEU fuels development program at the Argonne National Laboratory in order to increase the number of reactors that can convert to use LEU without significant detriment to their performance

Multiple unit root tests under uncertainty over the initial condition : some powerful modifications

NARCIS (Netherlands)

Hanck, C.

We modify the union-of-rejection unit root test of Harvey et al. "Unit Root Testing in Practice: Dealing with Uncertainty over the Trend and Initial Condition" (Harvey, Econom Theory 25:587-636, 2009). This test rejects if either of two different unit root tests rejects but controls the inherent

Prototype radiographic system for emergency and intensive care units: Initial experience

International Nuclear Information System (INIS)

Mirvis, S.

1986-01-01

A prototype radiographic system has been developed for use in bedside examinations in multibed trauma or intensive care units and emergency rooms. The system features a single-phase, high-frequency 30-kW ceiling-mounted generator with an x-ray tube extending from a long counterbalanced arm. All movements are servo-assisted for ease of operation. Based on initial experience, the unit allows easier access to the patient around resuscitation and monitoring equipment, occupies less floor space, and yields better quality images than do standard mobile radiographic units

Hydrogen and fuel cells in the United States Congress

International Nuclear Information System (INIS)

Yacobucci, B.D.

2003-01-01

Over the past few years, the United States Congress has shown increasing interest in the development of hydrogen fuel and fuel cells for transportation, stationary, and mobile applications The high efficiency of fuel cell systems could address some of the concern over increasing dependence on imported petroleum. Further, lower emissions could help promote air quality goals However, many questions remain, including the affordability, safety, overall fuel-cycle efficiency and emissions. These questions, especially those related to cost, have led Members of Congress to enact legislation to speed the development and commercialization of the technologies. This paper discusses congressional action on hydrogen and fuel cells. It provides an overview of the U.S. Congress, and outlines the role of the appropriations process. It then provides a history of federal hydrogen fuel research and development (R and D), both in terms of legislative and executive initiatives, and it describes pending legislation current as of this writing, including bills on energy policy, transportation policy, tax policy, and appropriations. Finally, the paper presents some of the issues that the pending legislation may raise for industry. (author)

Unit cell geometry of 3-D braided structures

Science.gov (United States)

Du, Guang-Wu; Ko, Frank K.

1993-01-01

The traditional approach used in modeling of composites reinforced by three-dimensional (3-D) braids is to assume a simple unit cell geometry of a 3-D braided structure with known fiber volume fraction and orientation. In this article, we first examine 3-D braiding methods in the light of braid structures, followed by the development of geometric models for 3-D braids using a unit cell approach. The unit cell geometry of 3-D braids is identified and the relationship of structural parameters such as yarn orientation angle and fiber volume fraction with the key processing parameters established. The limiting geometry has been computed by establishing the point at which yarns jam against each other. Using this factor makes it possible to identify the complete range of allowable geometric arrangements for 3-D braided preforms. This identified unit cell geometry can be translated to mechanical models which relate the geometrical properties of fabric preforms to the mechanical responses of composite systems.

Initiation of Failure for Masonry Subject to In-Plane Loads through Micromechanics

Directory of Open Access Journals (Sweden)

V. P. Berardi

2016-01-01

Full Text Available A micromechanical procedure is used in order to evaluate the initiation of damage and failure of masonry with in-plane loads. Masonry material is viewed as a composite with periodic microstructure and, therefore, a unit cell with suitable boundary conditions is assumed as a representative volume element of the masonry. The finite element method is used to determine the average stress on the unit cell corresponding to a given average strain prescribed on the unit cell. Finally, critical curves representing the initiation of damage and failure in both clay brick masonry and adobe masonry are provided.

Genital Herpes - Initial Visits to Physicians' Offices, United States, 1966-2012

Science.gov (United States)

... Archive Data & Statistics Sexually Transmitted Diseases Figure 48. Genital Herpes — Initial Visits to Physicians’ Offices, United States, 1966 – ... Statistics page . NOTE : The relative standard errors for genital herpes estimates of more than 100,000 range from ...

A cost effective model for appropriate administration of red cell units and salvaging un-transfused red cell units by using temperature sensitive indicators for blood component transportation in a hospital setting

Directory of Open Access Journals (Sweden)

Aseem K Tiwari

2015-01-01

Full Text Available Background: A rule called "30-min rule" defines that red cell unit cannot be used if it has been out of blood bank refrigerator for over 30 min. This rule is useful to guide initiation of transfusion, but is inadequate for deciding whether to reuse or discard units received-back at blood transfusion services (BTS. A simple cost-effective temperature-sensitive indicator was evaluated to decide upon reuse (cold chain was uninterrupted or discard (where cold chain was interrupted in a simulation exercise. Materials and Methods: Temperature-sensitive indicators TH-F™ that irreversibly changed color from white to red demonstrated that heat excursion has occurred and the cumulative temperature has exceeded 10°C for over 30 min, were used in outdated red cells for simulating units, which are not used and received-back. These units were also tagged with a standard temperature monitoring device, which was a re-usable credit card sized device, which would log the actual time and temperature. In few units percent hemolysis was also calculated. Results: Statistically insignificant elevation in average temperature was noted in 102 simulated units at the time of return to BTS (Δ 0.04°C, despite the fact that these units were in the transport box for over 4 h. The average supernatant hemoglobin in these units was 0.24%, much below the prescribed threshold. Conclusion: Transportation of blood in controlled conditions with temperature-sensitive indicator is a cost-effective model to save blood, a precious human resource.

Buckling behavior of origami unit cell facets under compressive loads

Science.gov (United States)

Kshad, Mohamed Ali Emhmed; Naguib, Hani E.

2018-03-01

Origami structures as cores for sandwich structures are designed to withstand the compressive loads and to dissipate compressive energy. The deformation of the origami panels and the unit cell facets are the primary factors behind the compressive energy dissipation in origami structures. During the loading stage, the origami structures deform through the folding and unfolding process of the unit cell facets, and also through the plastic deformation of the facets. This work presents a numerical study of the buckling behavior of different origami unit cell elements under compressive loading. The studied origami configurations were Miura and Ron-Resch-like origami structures. Finite element package was used to model the origami structures. The study investigated the buckling behavior of the unit cell facets of two types of origami structures Miura origami and Ron-Resch-Like origami structures. The simulation was conducted using ANSYS finite element software, in which the model of the unit cell represented by shell elements, and the eigenvalues buckling solver was used to predict the theoretical buckling of the unit cell elements.

CD200-expressing human basal cell carcinoma cells initiate tumor growth.

Science.gov (United States)

Colmont, Chantal S; Benketah, Antisar; Reed, Simon H; Hawk, Nga V; Telford, William G; Ohyama, Manabu; Udey, Mark C; Yee, Carole L; Vogel, Jonathan C; Patel, Girish K

2013-01-22

Smoothened antagonists directly target the genetic basis of human basal cell carcinoma (BCC), the most common of all cancers. These drugs inhibit BCC growth, but they are not curative. Although BCC cells are monomorphic, immunofluorescence microscopy reveals a complex hierarchical pattern of growth with inward differentiation along hair follicle lineages. Most BCC cells express the transcription factor KLF4 and are committed to terminal differentiation. A small CD200(+) CD45(-) BCC subpopulation that represents 1.63 ± 1.11% of all BCC cells resides in small clusters at the tumor periphery. By using reproducible in vivo xenograft growth assays, we determined that tumor initiating cell frequencies approximate one per 1.5 million unsorted BCC cells. The CD200(+) CD45(-) BCC subpopulation recreated BCC tumor growth in vivo with typical histological architecture and expression of sonic hedgehog-regulated genes. Reproducible in vivo BCC growth was achieved with as few as 10,000 CD200(+) CD45(-) cells, representing ~1,500-fold enrichment. CD200(-) CD45(-) BCC cells were unable to form tumors. These findings establish a platform to study the effects of Smoothened antagonists on BCC tumor initiating cell and also suggest that currently available anti-CD200 therapy be considered, either as monotherapy or an adjunct to Smoothened antagonists, in the treatment of inoperable BCC.

Initial closed operation of the CELSS Test Facility Engineering Development Unit

Science.gov (United States)

Kliss, M.; Blackwell, C.; Zografos, A.; Drews, M.; MacElroy, R.; McKenna, R.; Heyenga, A. G.

2003-01-01

As part of the NASA Advanced Life Support Flight Program, a Controlled Ecological Life Support System (CELSS) Test Facility Engineering Development Unit has been constructed and is undergoing initial operational testing at NASA Ames Research Center. The Engineering Development Unit (EDU) is a tightly closed, stringently controlled, ground-based testbed which provides a broad range of environmental conditions under which a variety of CELSS higher plant crops can be grown. Although the EDU was developed primarily to provide near-term engineering data and a realistic determination of the subsystem and system requirements necessary for the fabrication of a comparable flight unit, the EDU has also provided a means to evaluate plant crop productivity and physiology under controlled conditions. This paper describes the initial closed operational testing of the EDU, with emphasis on the hardware performance capabilities. Measured performance data during a 28-day closed operation period are compared with the specified functional requirements, and an example of inferring crop growth parameters from the test data is presented. Plans for future science and technology testing are also discussed. Published by Elsevier Science Ltd on behalf of COSPAR.

Imaging Reporters for Proteasome Activity Identify Tumor- and Metastasis-Initiating Cells

Directory of Open Access Journals (Sweden)

Amanda C. Stacer

2015-08-01

Full Text Available Tumor-initiating cells, also designated as cancer stem cells, are proposed to constitute a subpopulation of malignant cells central to tumorigenesis, metastasis, and treatment resistance. We analyzed the activity of the proteasome, the primary organelle for targeted protein degradation, as a marker of tumor- and metastasis-initiating cells. Using human and mouse breast cancer cells expressing a validated fluorescent reporter, we found a small subpopulation of cells with low proteasome activity that divided asymmetrically to produce daughter cells with low or high proteasome activity. Breast cancer cells with low proteasome activity had greater local tumor formation and metastasis in immunocompromised and immunocompetent mice. To allow flexible labeling of cells, we also developed a new proteasome substrate based on HaloTag technology. Patient-derived glioblastoma cells with low proteasome activity measured by the HaloTag reporter show key phenotypes associated with tumor-initiating cells, including expression of a stem cell transcription factor, reconstitution of the original starting population, and enhanced neurosphere formation. We also show that patient-derived glioblastoma cells with low proteasome activity have higher frequency of tumor formation in mouse xenografts. These studies support proteasome function as a tool to investigate tumor- and metastasis-initiating cancer cells and a potential biomarker for outcomes in patients with several different cancers.

Glioblastoma-Initiating Cells: Relationship with Neural Stem Cells and the Micro-Environment

OpenAIRE

Goffart, Nicolas; KROONEN, Jérôme

2013-01-01

Glioblastoma multiforme (GBM, WHO grade IV) is the most common and lethal subtype of primary brain tumor with a median overall survival of 15 months from the time of diagnosis. The presence in GBM of a cancer population displaying neural stem cell (NSC) properties as well as tumor-initiating abilities and resistance to current therapies suggests that these glioblastoma-initiating cells (GICs) play a central role in tumor development and are closely related to NSCs. However, it is nowadays sti...

Tobacco and e-cigarette products initiate Kupffer cell inflammatory responses.

Science.gov (United States)

Rubenstein, David A; Hom, Sarah; Ghebrehiwet, Berhane; Yin, Wei

2015-10-01

Kupffer cells are liver resident macrophages that are responsible for screening and clearing blood of pathogens and foreign particles. It has recently been shown that Kupffer cells interact with platelets, through an adhesion based mechanism, to aid in pathogen clearance and then these platelets re-enter the general systemic circulation. Thus, a mechanism has been identified that relates liver inflammation to possible changes in the systemic circulation. However, the role that Kupffer cells play in cardiovascular disease initiation/progression has not been elucidated. Thus, our objective was to determine whether or not Kupffer cells are responsive to a classical cardiovascular risk factor and if these changes can be transmitted into the general systemic circulation. If Kupffer cells initiate inflammatory responses after exposure to classical cardiovascular risk factors, then this provides a potential alternative/synergistic pathway for cardiovascular disease initiation. We aimed to elucidate the prevalence of this potential pathway. We hypothesized that Kupffer cells would initiate a robust inflammatory response after exposure to tobacco cigarette or e-cigarette products and that the inflammatory response would have the potential to antagonize other salient cells for cardiovascular disease progression. To test this, Kupffer cells were incubated with tobacco smoke extracts, e-cigarette vapor extracts or pure nicotine. Complement deposition onto Kupffer cells, Kupffer cell complement receptor expression, oxidative stress production, cytokine release and viability and density were assessed after the exposure. We observed a robust inflammatory response, oxidative stress production and cytokine release after Kupffer cells were exposed to tobacco or e-cigarette extracts. We also observed a marginal decrease in cell viability coupled with a significant decrease in cell density. In general, this was not a function of the extract formulation (e.g. tobacco vs. e

Fabrication and characteristics of unit cell for SOFC

Energy Technology Data Exchange (ETDEWEB)

Kim, Gwi-Yeol; Eom, Seung-Wook; Moon, Seong-In [Korea Electrotechnology Research Institute, Kyongnam (Korea, Republic of)] [and others

1996-12-31

Research and development on solid oxide fuel cells in Korea have been mainly focused on unit cell and small stack. Fuel cell system is called clean generation system which not cause NOx or SOx. It is generation efficiency come to 50-60% in contrast to 40% of combustion generation system. Among the fuel cell system, solid oxide fuel cell is constructed of ceramics, so stack construction is simple, power density is very high, and there are no corrosion problems. The object of this study is to develop various composing material for SOFC generation system, and to test unit cell performance manufactured. So we try to present a guidance for developing mass power generation system. We concentrated on development of manufacturing process for cathode, anode and electrolyte.

Initial startup and operations of Yonggwang Units 3 and 4

International Nuclear Information System (INIS)

Collier, T.J.; Chari, D.R.; Kiraly, F.

1996-01-01

A significant milestone in the nuclear power industry was achieved in 1995, when Yonggwang (YGN) Units 3 and 4 were accepted into in commercial operation by Korea Electric Power Corporation (KEPCO). YGN Unit 3 was accepted into commercial operation on March 31, 1995, the original date established during project initiation. YGN Unit 4 was accepted into operation on January 1, 1996, 3 months ahead of schedule. Each YGN unit produces approximately 1,050 Mwe and supplies approximately ten percent of the total electric power demand in the Republic of Korea (ROK). The overall plant efficiency is approximately 37% which is at least 1% higher than most nuclear units. Since achieving commercial operation, YGN Unit 3 has operated at essentially full power which has resulted in an annual performance rate in excess of 85%. YGN Unit 3 is the first of six pressurized water reactors which are currently under design and construction in the ROK and serves as the reference design for the Korean Standard Nuclear Power Plant program. Both YGN Units 3 and 4 include a System 800 Nuclear Steam Supply System (NSSS). The NSSS is rated at 2,815 Mwth and is the ABB-CE standard design. The design includes numerous advanced design features which enhance plant safety, performance and operability. A well executed startup test program was successfully completed on both units prior to commercial operation. A summary of the YGN NSSS design features, the startup test program and selected test results demonstrating the performance of those features are presented in this paper

ACO-Initialized Wavelet Neural Network for Vibration Fault Diagnosis of Hydroturbine Generating Unit

OpenAIRE

Xiao, Zhihuai; He, Xinying; Fu, Xiangqian; Malik, O. P.

2015-01-01

Considering the drawbacks of traditional wavelet neural network, such as low convergence speed and high sensitivity to initial parameters, an ant colony optimization- (ACO-) initialized wavelet neural network is proposed in this paper for vibration fault diagnosis of a hydroturbine generating unit. In this method, parameters of the wavelet neural network are initialized by the ACO algorithm, and then the wavelet neural network is trained by the gradient descent algorithm. Amplitudes of the fr...

Neuroblastoma cell lines contain pluripotent tumor initiating cells that are susceptible to a targeted oncolytic virus.

Directory of Open Access Journals (Sweden)

Yonatan Y Mahller

Full Text Available Although disease remission can frequently be achieved for patients with neuroblastoma, relapse is common. The cancer stem cell theory suggests that rare tumorigenic cells, resistant to conventional therapy, are responsible for relapse. If true for neuroblastoma, improved cure rates may only be achieved via identification and therapeutic targeting of the neuroblastoma tumor initiating cell. Based on cues from normal stem cells, evidence for tumor populating progenitor cells has been found in a variety of cancers.Four of eight human neuroblastoma cell lines formed tumorspheres in neural stem cell media, and all contained some cells that expressed neurogenic stem cell markers including CD133, ABCG2, and nestin. Three lines tested could be induced into multi-lineage differentiation. LA-N-5 spheres were further studied and showed a verapamil-sensitive side population, relative resistance to doxorubicin, and CD133+ cells showed increased sphere formation and tumorigenicity. Oncolytic viruses, engineered to be clinically safe by genetic mutation, are emerging as next generation anticancer therapeutics. Because oncolytic viruses circumvent typical drug-resistance mechanisms, they may represent an effective therapy for chemotherapy-resistant tumor initiating cells. A Nestin-targeted oncolytic herpes simplex virus efficiently replicated within and killed neuroblastoma tumor initiating cells preventing their ability to form tumors in athymic nude mice.These results suggest that human neuroblastoma contains tumor initiating cells that may be effectively targeted by an oncolytic virus.

Leukemia-Initiating Cells in T-Cell Acute Lymphoblastic Leukemia.

Science.gov (United States)

Tan, Shi Hao; Bertulfo, Fatima Carla; Sanda, Takaomi

2017-01-01

T-cell acute lymphoblastic leukemia (T-ALL) is a hematological malignancy characterized by the clonal proliferation of immature T-cell precursors. T-ALL has many similar pathophysiological features to acute myeloid leukemia, which has been extensively studied in the establishment of the cancer stem cell (CSC) theory, but the CSC concept in T-ALL is still debatable. Although leukemia-initiating cells (LICs), which can generate leukemia in a xenograft setting, have been found in both human T-ALL patients and animal models, the nature and origin of LICs are largely unknown. In this review, we discuss recent studies on LICs in T-ALL and the potential mechanisms of LIC emergence in this disease. We focus on the oncogenic transcription factors TAL1, LMO2 , and NOTCH1 and highlight the significance of the transcriptional regulatory programs in normal hematopoietic stem cells and T-ALL.

Leukemia-Initiating Cells in T-Cell Acute Lymphoblastic Leukemia

Directory of Open Access Journals (Sweden)

Shi Hao Tan

2017-09-01

Full Text Available T-cell acute lymphoblastic leukemia (T-ALL is a hematological malignancy characterized by the clonal proliferation of immature T-cell precursors. T-ALL has many similar pathophysiological features to acute myeloid leukemia, which has been extensively studied in the establishment of the cancer stem cell (CSC theory, but the CSC concept in T-ALL is still debatable. Although leukemia-initiating cells (LICs, which can generate leukemia in a xenograft setting, have been found in both human T-ALL patients and animal models, the nature and origin of LICs are largely unknown. In this review, we discuss recent studies on LICs in T-ALL and the potential mechanisms of LIC emergence in this disease. We focus on the oncogenic transcription factors TAL1, LMO2, and NOTCH1 and highlight the significance of the transcriptional regulatory programs in normal hematopoietic stem cells and T-ALL.

Glioblastoma-Initiating Cells: Relationship with Neural Stem Cells and the Micro-Environment

Energy Technology Data Exchange (ETDEWEB)

Goffart, Nicolas [Laboratory of Developmental Neurobiology, GIGA-Neurosciences Research Center, University of Liège, Liège 4000 (Belgium); Kroonen, Jérôme [Human Genetics, CHU and University of Liège, Liège 4000 (Belgium); The T& P Bohnenn Laboratory for Neuro-Oncology, Department of Neurology and Neurosurgery, UMC Utrecht, Utrecht 3556 (Netherlands); Rogister, Bernard, E-mail: Bernard.Register@ulg.ac.be [Laboratory of Developmental Neurobiology, GIGA-Neurosciences Research Center, University of Liège, Liège 4000 (Belgium); Department of Neurology, CHU and University of Liège, Liège 4000 (Belgium); GIGA-Development, Stem Cells and Regenerative Medicine, University of Liège, Liège 4000 (Belgium)

2013-08-14

Glioblastoma multiforme (GBM, WHO grade IV) is the most common and lethal subtype of primary brain tumor with a median overall survival of 15 months from the time of diagnosis. The presence in GBM of a cancer population displaying neural stem cell (NSC) properties as well as tumor-initiating abilities and resistance to current therapies suggests that these glioblastoma-initiating cells (GICs) play a central role in tumor development and are closely related to NSCs. However, it is nowadays still unclear whether GICs derive from NSCs, neural progenitor cells or differentiated cells such as astrocytes or oligodendrocytes. On the other hand, NSCs are located in specific regions of the adult brain called neurogenic niches that have been shown to control critical stem cell properties, to nourish NSCs and to support their self-renewal. This “seed-and-soil” relationship has also been adapted to cancer stem cell research as GICs also require a specific micro-environment to maintain their “stem cell” properties. In this review, we will discuss the controversies surrounding the origin and the identification of GBM stem cells and highlight the micro-environment impact on their biology.

Glioblastoma-Initiating Cells: Relationship with Neural Stem Cells and the Micro-Environment

International Nuclear Information System (INIS)

Goffart, Nicolas; Kroonen, Jérôme; Rogister, Bernard

2013-01-01

Glioblastoma multiforme (GBM, WHO grade IV) is the most common and lethal subtype of primary brain tumor with a median overall survival of 15 months from the time of diagnosis. The presence in GBM of a cancer population displaying neural stem cell (NSC) properties as well as tumor-initiating abilities and resistance to current therapies suggests that these glioblastoma-initiating cells (GICs) play a central role in tumor development and are closely related to NSCs. However, it is nowadays still unclear whether GICs derive from NSCs, neural progenitor cells or differentiated cells such as astrocytes or oligodendrocytes. On the other hand, NSCs are located in specific regions of the adult brain called neurogenic niches that have been shown to control critical stem cell properties, to nourish NSCs and to support their self-renewal. This “seed-and-soil” relationship has also been adapted to cancer stem cell research as GICs also require a specific micro-environment to maintain their “stem cell” properties. In this review, we will discuss the controversies surrounding the origin and the identification of GBM stem cells and highlight the micro-environment impact on their biology

Glioblastoma-Initiating Cells: Relationship with Neural Stem Cells and the Micro-Environment

Directory of Open Access Journals (Sweden)

Nicolas Goffart

2013-08-01

Full Text Available Glioblastoma multiforme (GBM, WHO grade IV is the most common and lethal subtype of primary brain tumor with a median overall survival of 15 months from the time of diagnosis. The presence in GBM of a cancer population displaying neural stem cell (NSC properties as well as tumor-initiating abilities and resistance to current therapies suggests that these glioblastoma-initiating cells (GICs play a central role in tumor development and are closely related to NSCs. However, it is nowadays still unclear whether GICs derive from NSCs, neural progenitor cells or differentiated cells such as astrocytes or oligodendrocytes. On the other hand, NSCs are located in specific regions of the adult brain called neurogenic niches that have been shown to control critical stem cell properties, to nourish NSCs and to support their self-renewal. This “seed-and-soil” relationship has also been adapted to cancer stem cell research as GICs also require a specific micro-environment to maintain their “stem cell” properties. In this review, we will discuss the controversies surrounding the origin and the identification of GBM stem cells and highlight the micro-environment impact on their biology.

The intrusive growth of initial cells in re-arangement of cells in cambium of Tilia cordata Mill.

Directory of Open Access Journals (Sweden)

Wiesław Włoch

2014-01-01

Full Text Available In the cambium of linden producing wood with short period of grain inclination change (2-4 years, the intensive reorientation of cells takes place. This is possible mainly through an intrusive growth of cell ends from one radial file entering space between tangential walls of neighboring file and through unequal periclinal divisions that occur in the "initial surface". The intrusive growth is located on the longitudinal edge of a fusiform cell close to the end, and causes deviation of cell ends in a neighbouring file from the initial surface. Unequal periclinal division divides a cell with a deviated end into two derivatives, unequal in size. The one of them, which inherits the deviated end, leaves the initial surface becoming a xylem or phloem mother cell. This means that the old end is eliminated. The intensity of intrusive growth and unequal periclinal divisions is decisive for the velocity of cambial cell reorientation. The oriented intrusive growth occurs only in the initial cells. For that reason, changes in cell-ends position do not occur within one packet of cells but are distinct between neighbouring packets.

The contribution to site core damage frequency from independent occurrences of initiators in two or more units: How low is it?

Energy Technology Data Exchange (ETDEWEB)

Kim, Dong-San; Park, Jin Hee; Lim, Ho Gon [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

2016-10-15

Stutzke estimated the site risk by summing the contribution from common cause initiators and the contribution from single-unit initiators. He considered some kinds of multi-unit accident sequences caused by single-unit initiators. However, the contribution from independent occurrences of initiators in two or more units at a site was not taken into account. The purpose of this study is to estimate the contribution to site core damage frequency (CDF) from simultaneous occurrences of independent initiators in two or more units at the same site. Some assumptions and methods used in this analysis are firstly described, and the results and conclusions of the analysis are described. In this study, the contribution to site core damage frequency (CDF) from simultaneous occurrences of independent initiators in two or more units at the same site was estimated. A Korean six-unit site was selected as the reference site and the at-power internal events Level 1 PSA model for an OPR1000 unit at the reference site was used as the base model, and was modified to deal with some major dependencies between units at the site. Specifically, the availability of the AAC D/G, dependencies between offsite power recovery actions in different unis, and inter-unit CCF modeling for risk-significant components such as diesel generators were taken into account. As a result, the sum of dual-unit CDF due to independent occurrences of initiators in two units at the reference site was estimated to be sufficiently low to be neglected.

40 CFR 63.9620 - On which units and by what date must I conduct performance tests or other initial compliance...

Science.gov (United States)

2010-07-01

... units and by what date must I conduct performance tests or other initial compliance demonstrations? (a... similar emission units together and conduct an initial compliance test on one representative emission unit... meet the criteria in paragraph (f) of this section. If you decide to test representative emission units...

The effect of initial cell concentration on xylose fermentation by Pichia stipitis

Science.gov (United States)

Frank K. Agbogbo; Guillermo Coward-Kelly; Mads Torry-Smith; Kevin Wenger; Thomas W. Jeffries

2007-01-01

Xylose was fermented using Pichia stipitis CBS 6054 at different initial cell concentrations. A high initial cell concentration increased the rate of xylose utilization, ethanol formation, and the ethanol yield. The highest ethanol concentration of 41.0 g/L and a yield of 0.38 g/g was obtained using an initial cell concentration of 6.5 g/L. Even though more xylitol was...

Cell phone recycling experiences in the United States and potential recycling options in Brazil.

Science.gov (United States)

Silveira, Geraldo T R; Chang, Shoou-Yuh

2010-11-01

This paper presents an overview of cell phone recycling programs currently available in the United States. At the same time, it also provides analyses of the current recycling situation and possible recycling alternatives for Brazil. Although there are several recycling options in the United States, collection rates are still only 10% of all potential devices because customers are not aware of these possibilities. The whole system is financially based on reselling refurbished cell phones and recycled materials to developing countries which represent an effective and strong market. Several recyclers offer funds to collection partners who are either charities or who work with charities while obtaining the materials that they need in order to run their operations. A mobile phone recycling system for Brazil considering the United States experience and the Extended Producer Responsibility (EPR) principle is suggested. A deposit/refund/advance-recycling fee is proposed which might be implemented as a voluntary industrial initiative managed by PRO Brazil, a producer responsibility organization. One widespread public-private agreement will integrate all mobile phone stakeholders, and environmental education actions and promotional events will promote citizen's participation. Copyright © 2010 Elsevier Ltd. All rights reserved.

Cooperative effects of fibronectin matrix assembly and initial cell-substrate adhesion strength in cellular self-assembly.

Science.gov (United States)

Brennan, James R; Hocking, Denise C

2016-03-01

organize cells into modular building blocks for artificial tissue fabrication. Fibronectin is an ECM protein that plays a key role in tissue formation during embryonic development. Additionally, the cell-mediated process of converting soluble fibronectin into insoluble, ECM-associated fibrils has been shown to initiate cellular self-assembly in vitro. In this study, we examine the relationship between the strength of cell-substrate adhesions and the ability of fibronectin fibril assembly to induce cellular self-assembly. Our results indicate that substrate composition and density play cooperative roles with cell-mediated fibronectin matrix assembly to control the transition of cells from 2D monolayers into 3D multicellular aggregates. Results of this study provide a quantitative approach to build predictive models of cellular self-assembly, as well as a simple cell-culture platform to produce biomimetic units for modular tissue engineering. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Comparison of gas membrane separation cascades using conventional separation cell and two-unit separation cells

International Nuclear Information System (INIS)

Ohno, Masayoshi; Morisue, Tetsuo; Ozaki, Osamu; Miyauchi, Terukatsu.

1978-01-01

The adoption of two-unit separation cells in radioactive rare gas membrane separation equipment enhances the separation factor, but increases the required membrane area and compressive power. An analytical economic evaluation was undertaken to compare the conventional separation cell with the two-unit separation cells, adopting as parameters the number of cascade stages, the membrane area and the operating power requirements. This paper describes the models used for evaluating the separation performance and the economics of cascade embodying these different concepts of separation cell taken up for study, and the results obtained for the individual concepts are mutually compared. It proved that, in respect of the number required of cascade stages, of operating power requirements and of the annual expenditure, better performance could always be expected of the two-unit separation cells as compared with the conventional separation cell, at least in the range of parameters adopted in this study. As regards the minimum membrane area, the conventional separation cell and the series-type separation cell yielded almost the same values, with the parallel-type separation cell falling somewhat behind. (auth.)

Initial quantitative evaluation of computed radiography in an intensive care unit

International Nuclear Information System (INIS)

Hillis, D.J.; McDonald, I.G.; Kelly, W.J.

1996-01-01

The first computed radiography (CR) unit in Australia was installed at St Vincent's Hospital, Melbourne, in February 1994. An initial qualitative evaluation of the attitude of the intensive care unit (ICU) physicians to the CR unit was conducted by use of a survey. The results of the survey of ICU physicians indicated that images were available faster than under the previous system and that the use of the CR system was preferred to evaluate chest tubes and line placements. While it is recognized that a further detailed radiological evaluation of the CR system is required to establish the diagnostic performance of CR compared with conventional film, some comments on the implementation of the system and ICU physician attitudes to the CR system are put forward for consideration by other hospitals examining the possible use of CR systems. 11 refs., 1 tab

Mechanical behavior of regular open-cell porous biomaterials made of diamond lattice unit cells.

Science.gov (United States)

Ahmadi, S M; Campoli, G; Amin Yavari, S; Sajadi, B; Wauthle, R; Schrooten, J; Weinans, H; Zadpoor, A A

2014-06-01

Cellular structures with highly controlled micro-architectures are promising materials for orthopedic applications that require bone-substituting biomaterials or implants. The availability of additive manufacturing techniques has enabled manufacturing of biomaterials made of one or multiple types of unit cells. The diamond lattice unit cell is one of the relatively new types of unit cells that are used in manufacturing of regular porous biomaterials. As opposed to many other types of unit cells, there is currently no analytical solution that could be used for prediction of the mechanical properties of cellular structures made of the diamond lattice unit cells. In this paper, we present new analytical solutions and closed-form relationships for predicting the elastic modulus, Poisson׳s ratio, critical buckling load, and yield (plateau) stress of cellular structures made of the diamond lattice unit cell. The mechanical properties predicted using the analytical solutions are compared with those obtained using finite element models. A number of solid and porous titanium (Ti6Al4V) specimens were manufactured using selective laser melting. A series of experiments were then performed to determine the mechanical properties of the matrix material and cellular structures. The experimentally measured mechanical properties were compared with those obtained using analytical solutions and finite element (FE) models. It has been shown that, for small apparent density values, the mechanical properties obtained using analytical and numerical solutions are in agreement with each other and with experimental observations. The properties estimated using an analytical solution based on the Euler-Bernoulli theory markedly deviated from experimental results for large apparent density values. The mechanical properties estimated using FE models and another analytical solution based on the Timoshenko beam theory better matched the experimental observations. Copyright © 2014 Elsevier Ltd

Characterisation of mesothelioma-initiating cells and their susceptibility to anti-cancer agents.

Directory of Open Access Journals (Sweden)

Elham Alizadeh Pasdar

Full Text Available Malignant mesothelioma (MM is an aggressive type of tumour causing high mortality. One reason for this paradigm may be the existence of a subpopulation of tumour-initiating cells (TICs that endow MM with drug resistance and recurrence. The objective of this study was to identify and characterise a TIC subpopulation in MM cells, using spheroid cultures, mesospheres, as a model of MM TICs. Mesospheres, typified by the stemness markers CD24, ABCG2 and OCT4, initiated tumours in immunodeficient mice more efficiently than adherent cells. CD24 knock-down cells lost the sphere-forming capacity and featured lower tumorigenicity. Upon serial transplantation, mesospheres were gradually more efficiently tumrigenic with increased level of stem cell markers. We also show that mesospheres feature mitochondrial and metabolic properties similar to those of normal and cancer stem cells. Finally, we show that mesothelioma-initiating cells are highly susceptible to mitochondrially targeted vitamin E succinate. This study documents that mesospheres can be used as a plausible model of mesothelioma-initiating cells and that they can be utilised in the search for efficient agents against MM.

The BRAIN Initiative Cell Census Consortium: Lessons Learned toward Generating a Comprehensive Brain Cell Atlas.

Science.gov (United States)

Ecker, Joseph R; Geschwind, Daniel H; Kriegstein, Arnold R; Ngai, John; Osten, Pavel; Polioudakis, Damon; Regev, Aviv; Sestan, Nenad; Wickersham, Ian R; Zeng, Hongkui

2017-11-01

A comprehensive characterization of neuronal cell types, their distributions, and patterns of connectivity is critical for understanding the properties of neural circuits and how they generate behaviors. Here we review the experiences of the BRAIN Initiative Cell Census Consortium, ten pilot projects funded by the U.S. BRAIN Initiative, in developing, validating, and scaling up emerging genomic and anatomical mapping technologies for creating a complete inventory of neuronal cell types and their connections in multiple species and during development. These projects lay the foundation for a larger and longer-term effort to generate whole-brain cell atlases in species including mice and humans. Copyright © 2017 Elsevier Inc. All rights reserved.

Fuel cell collaboration in the United States. Follow up report to the Danish Partnership for Hydrogen and Fuel Cells

Energy Technology Data Exchange (ETDEWEB)

NONE

2013-01-15

Fuel cell technology continues to grow in the United States, with strong sales in stationary applications and early markets such as data centers, materials handling equipment, and telecommunications sites. New fuel cell customers include Fortune 500 companies Apple, eBay, Coca-Cola, and Walmart, who will use fuel cells to provide reliable power to data centers, stores, and facilities. Some are purchasing multi-megawatt (MW) systems, including three of the largest non-utility purchases of stationary fuel cells in the world by AT and T, Apple and eBay - 17 MW, 10 MW and 6 MW respectively. Others are replacing fleets of battery forklifts with fuel cells. Sysco, the food distributor, has more than 700 fuel cell-powered forklifts operating at seven facilities, with more on order. Mega-retailer Walmart now operates more than 500 fuel cell forklifts at three warehouses, including a freezer facility. Although federal government budget reduction efforts are impacting a wide range of departments and programs, fuel cell and hydrogen technology continues to be funded, albeit at a lower level than in past years. The Department of Energy (DOE) is currently funding fuel cell and hydrogen R and D and has nearly 300 ongoing projects at companies, national labs, and universities/institutes universities. The American Recovery and Reinvestment Act (ARRA) of 2009 and DOE's Market Transformation efforts have acted as a government ''catalyst'' for market success of emerging technologies. Early market deployments of about 1,400 fuel cells under the ARRA have led to more than 5,000 additional fuel cell purchases by industry with no DOE funding. In addition, interest in Congress remains high. Senators Richard Blumenthal (D-CT), Chris Coons (D-DE), Lindsey Graham (R-SC) and John Hoeven (R-ND) re-launched the bipartisan Senate Fuel Cell and Hydrogen Caucus in August 2012 to promote the continued development and commercialization of hydrogen and fuel cell technologies

Unusually large unit cell of lipid bicontinuous cubic phase: towards nature's length scales

Science.gov (United States)

Kim, Hojun; Leal, Cecilia

Lipid bicontinuous cubic phases are of great interest for drug delivery, protein crystallization, biosensing, and templates for directing hard material assembly. Structural modulations of lipid mesophases regarding phase identity and unit cell size are often necessary to augment loading and gain pore size control. One important example is the need for unit cells large enough to guide the crystallization of bigger proteins without distortion of the templating phase. In nature, bicontinuous cubic constructs achieve unit cell dimensions as high as 300 nm. However, the largest unit cell of lipid mesophases synthesized in the lab is an order of magnitude lower. In fact, it has been predicted theoretically that lipid bicontinuous cubic phases of unit cell dimensions exceeding 30 nm could not exist, as high membrane fluctuations would damp liquid crystalline order. Here we report non-equilibrium assembly methods of synthesizing metastable bicontinuous cubic phases with unit cell dimensions as high as 70 nm. The phases are stable for very long periods and become increasingly ordered as time goes by without changes to unit cell dimensions. We acknowledge the funding source as a NIH.

Elucidation of Altered Pathways in Tumor-Initiating Cells of Triple-Negative Breast Cancer: A Useful Cell Model System for Drug Screening.

Science.gov (United States)

Christensen, Anne G; Ehmsen, Sidse; Terp, Mikkel G; Batra, Richa; Alcaraz, Nicolas; Baumbach, Jan; Noer, Julie B; Moreira, José; Leth-Larsen, Rikke; Larsen, Martin R; Ditzel, Henrik J

2017-08-01

A limited number of cancer cells within a tumor are thought to have self-renewing and tumor-initiating capabilities that produce the remaining cancer cells in a heterogeneous tumor mass. Elucidation of central pathways preferentially used by tumor-initiating cells/cancer stem cells (CSCs) may allow their exploitation as potential cancer therapy targets. We used single cell cloning to isolate and characterize four isogenic cell clones from a triple-negative breast cancer cell line; two exhibited mesenchymal-like and two epithelial-like characteristics. Within these pairs, one, but not the other, resulted in tumors in immunodeficient NOD/Shi-scid/IL-2 Rγ null mice and efficiently formed mammospheres. Quantitative proteomics and phosphoproteomics were used to map signaling pathways associated with the tumor-initiating ability. Signaling associated with apoptosis was suppressed in tumor-initiating versus nontumorigenic counterparts with pro-apoptotic proteins, such as Bcl2-associated agonist of cell death (BAD), FAS-associated death domain protein (FADD), and myeloid differentiation primary response protein (MYD88), downregulated in tumor-initiating epithelial-like cells. Functional studies confirmed significantly lower apoptosis in tumor-initiating versus nontumorigenic cells. Moreover, central pathways, including β-catenin and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)-related signaling, exhibited increased activation in the tumor-initiating cells. To evaluate the CSC model as a tool for drug screening, we assessed the effect of separately blocking NF-κB and Wnt/β-catenin signaling and found markedly reduced mammosphere formation, particularly for tumor-initiating cells. Similar reduction was also observed using patient-derived primary cancer cells. Furthermore, blocking NF-κB signaling in mice transplanted with tumor-initiating cells significantly reduced tumor outgrowth. Our study demonstrates that suppressed apoptosis, activation

Advanced fuel cell development in the United States

International Nuclear Information System (INIS)

Ackerman, J.P.

1984-01-01

Both molten carbonate and solid oxide fuel cells are being developed in the United States to complement and/or supplant phosphoric acid cells for commercial and utility use. This paper described the two technologies and the programs for their development

Analysis of long-time operation of micro-cogeneration unit with fuel cell

Directory of Open Access Journals (Sweden)

Patsch Marek

2015-01-01

Full Text Available Micro-cogeneration is cogeneration with small performance, with maximal electric power up to 50 kWe. On the present, there are available small micro-cogeneration units with small electric performance, about 1 kWe, which are usable also in single family houses or flats. These micro-cogeneration units operate on principle of conventional combustion engine, Stirling engine, steam engine or fuel cell. Micro-cogeneration units with fuel cells are new progressive developing type of units for single family houses. Fuel cell is electrochemical device which by oxidation-reduction reaction turn directly chemical energy of fuel to electric power, secondary products are pure water and thermal energy. The aim of paper is measuring and evaluation of operation parameters of micro-cogeneration unit with fuel cell which uses natural gas as a fuel.

Association Between Direct-to-Consumer Advertising and Testosterone Testing and Initiation in the United States, 2009-2013.

Science.gov (United States)

Layton, J Bradley; Kim, Yoonsang; Alexander, G Caleb; Emery, Sherry L

2017-03-21

Testosterone initiation increased substantially in the United States from 2000 to 2013, especially among men without clear indications. Direct-to-consumer advertising (DTCA) also increased during this time. To investigate associations between televised DTCA and testosterone testing and initiation in the United States. Ecologic study conducted in designated market areas (DMAs) in the United States. Monthly testosterone advertising ratings were linked to DMA-level testosterone use data from 2009-2013 derived from commercial insurance claims. Associations between DTCA and testosterone testing, initiation, and initiation without recent baseline tests were estimated using Poisson generalized estimating equations. Monthly Nielsen ratings for testosterone DTCA in the 75 largest DMAs. (1) Rates of new serum testosterone testing; (2) rates of testosterone initiation (in-office injection, surgical implant, or pharmacy dispensing) for all testosterone products combined and for specific brands; and (3) rates of testosterone initiation without recent serum testosterone testing. Of 17 228 599 commercially insured men in the 75 DMAs, 1 007 990 (mean age, 49.6 [SD, 11.5] years) had new serum testosterone tests and 283 317 (mean age, 51.8 [SD, 11.3] years) initiated testosterone treatment. Advertising intensity varied by geographic region and time, with the highest intensity seen in the southeastern United States and with months ranging from no ad exposures to a mean of 13.6 exposures per household. Nonbranded advertisements were common prior to 2012, with branded advertisements becoming more common during and after 2012. Each household advertisement exposure was associated with a monthly increase in rates of new testosterone testing (rate ratio [RR], 1.006; 95% CI, 1.004-1.008), initiation (RR, 1.007; 95% CI, 1.004-1.010), and initiation without a recent test (RR, 1.008; 95% CI, 1.002-1.013). Mean absolute rate increases were 0.14 tests (95% CI, 0.09-0.19), 0.05 new

Hydrogen Fuel Cell Performance as Telecommunications Backup Power in the United States

Energy Technology Data Exchange (ETDEWEB)

Kurtz, Jennifer [National Renewable Energy Lab. (NREL), Golden, CO (United States); Saur, Genevieve [National Renewable Energy Lab. (NREL), Golden, CO (United States); Sprik, Sam [National Renewable Energy Lab. (NREL), Golden, CO (United States)

2015-03-01

Working in collaboration with the U.S. Department of Energy (DOE) and industry project partners, the National Renewable Energy Laboratory (NREL) acts as the central data repository for the data collected from real-world operation of fuel cell backup power systems. With American Recovery and Reinvestment Act of 2009 (ARRA) co-funding awarded through DOE's Fuel Cell Technologies Office, more than 1,300 fuel cell units were deployed over a three-plus-year period in stationary, material handling equipment, auxiliary power, and backup power applications. This surpassed a Fuel Cell Technologies Office ARRA objective to spur commercialization of an early market technology by installing 1,000 fuel cell units across several different applications, including backup power. By December 2013, 852 backup power units out of 1,330 fuel cell units deployed were providing backup service, mainly for telecommunications towers. For 136 of the fuel cell backup units, project participants provided detailed operational data to the National Fuel Cell Technology Evaluation Center for analysis by NREL's technology validation team. NREL analyzed operational data collected from these government co-funded demonstration projects to characterize key fuel cell backup power performance metrics, including reliability and operation trends, and to highlight the business case for using fuel cells in these early market applications. NREL's analyses include these critical metrics, along with deployment, U.S. grid outage statistics, and infrastructure operation.

Initial fluid resuscitation of patients with septic shock in the intensive care unit

DEFF Research Database (Denmark)

Carlsen, Sarah; Perner, A

2011-01-01

Fluid is the mainstay of resuscitation of patients with septic shock, but the optimal composition and volume are unknown. Our aim was to evaluate the current initial fluid resuscitation practice in patients with septic shock in the intensive care unit (ICU) and patient characteristics and outcome...

Initiation of Antiviral B Cell Immunity Relies on Innate Signals from Spatially Positioned NKT Cells.

Science.gov (United States)

Gaya, Mauro; Barral, Patricia; Burbage, Marianne; Aggarwal, Shweta; Montaner, Beatriz; Warren Navia, Andrew; Aid, Malika; Tsui, Carlson; Maldonado, Paula; Nair, Usha; Ghneim, Khader; Fallon, Padraic G; Sekaly, Rafick-Pierre; Barouch, Dan H; Shalek, Alex K; Bruckbauer, Andreas; Strid, Jessica; Batista, Facundo D

2018-01-25

B cells constitute an essential line of defense from pathogenic infections through the generation of class-switched antibody-secreting cells (ASCs) in germinal centers. Although this process is known to be regulated by follicular helper T (TfH) cells, the mechanism by which B cells initially seed germinal center reactions remains elusive. We found that NKT cells, a population of innate-like T lymphocytes, are critical for the induction of B cell immunity upon viral infection. The positioning of NKT cells at the interfollicular areas of lymph nodes facilitates both their direct priming by resident macrophages and the localized delivery of innate signals to antigen-experienced B cells. Indeed, NKT cells secrete an early wave of IL-4 and constitute up to 70% of the total IL-4-producing cells during the initial stages of infection. Importantly, the requirement of this innate immunity arm appears to be evolutionarily conserved because early NKT and IL-4 gene signatures also positively correlate with the levels of neutralizing antibodies in Zika-virus-infected macaques. In conclusion, our data support a model wherein a pre-TfH wave of IL-4 secreted by interfollicular NKT cells triggers the seeding of germinal center cells and serves as an innate link between viral infection and B cell immunity. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Tumor initiating cells in malignant gliomas: biology and implications for therapy.

Science.gov (United States)

Hadjipanayis, Costas G; Van Meir, Erwin G

2009-04-01

A rare subpopulation of cells within malignant gliomas, which shares canonical properties with neural stem cells (NSCs), may be integral to glial tumor development and perpetuation. These cells, also known as tumor initiating cells (TICs), have the ability to self-renew, develop into any cell in the overall tumor population (multipotency), and proliferate. A defining property of TICs is their ability to initiate new tumors in immunocompromised mice with high efficiency. Mounting evidence suggests that TICs originate from the transformation of NSCs and their progenitors. New findings show that TICs may be more resistant to chemotherapy and radiation than the bulk of tumor cells, thereby permitting recurrent tumor formation and accounting for the failure of conventional therapies. The development of new therapeutic strategies selectively targeting TICs while sparing NSCs may provide for more effective treatment of malignant gliomas.

The fundamental unit of pain is the cell.

Science.gov (United States)

Reichling, David B; Green, Paul G; Levine, Jon D

2013-12-01

The molecular/genetic era has seen the discovery of a staggering number of molecules implicated in pain mechanisms [18,35,61,69,96,133,150,202,224]. This has stimulated pharmaceutical and biotechnology companies to invest billions of dollars to develop drugs that enhance or inhibit the function of many these molecules. Unfortunately this effort has provided a remarkably small return on this investment. Inevitably, transformative progress in this field will require a better understanding of the functional links among the ever-growing ranks of "pain molecules," as well as their links with an even larger number of molecules with which they interact. Importantly, all of these molecules exist side-by-side, within a functional unit, the cell, and its adjacent matrix of extracellular molecules. To paraphrase a recent editorial in Science magazine [223], although we live in the Golden age of Genetics, the fundamental unit of biology is still arguably the cell, and the cell is the critical structural and functional setting in which the function of pain-related molecules must be understood. This review summarizes our current understanding of the nociceptor as a cell-biological unit that responds to a variety of extracellular inputs with a complex and highly organized interaction of signaling molecules. We also discuss the insights that this approach is providing into peripheral mechanisms of chronic pain and sex dependence in pain.

Heat and Mass Transfer during Hydrogen Generation in an Array of Fuel Bars of a BWR Using a Periodic Unit Cell

Directory of Open Access Journals (Sweden)

H. Romero-Paredes

2012-01-01

Full Text Available This paper presents, the numerical analysis of heat and mass transfer during hydrogen generation in an array of fuel cylinder bars, each coated with a cladding and a steam current flowing outside the cylinders. The analysis considers the fuel element without mitigation effects. The system consists of a representative periodic unit cell where the initial and boundary-value problems for heat and mass transfer were solved. In this unit cell, we considered that a fuel element is coated by a cladding with steam surrounding it as a coolant. The numerical simulations allow describing the evolution of the temperature and concentration profiles inside the nuclear reactor and could be used as a basis for hybrid upscaling simulations.

Importance of unit cells in accurate evaluation of the characteristics of graphene

Energy Technology Data Exchange (ETDEWEB)

Sabzyan, Hassan; Sadeghpour, Narges [Isfahan Univ. (Iran, Islamic Republic of). Dept. of Chemistry

2016-08-01

Effects of the size of the unit cell on energy, atomic charges, and phonon frequencies of graphene at the Γ point of the Brillouin zone are studied in the absence and presence of an electric field using density functional theory (DFT) methods (LDA and DFT-PBE functionals with Goedecker-Teter-Hutter (GTH) and Troullier-Martins (TM) norm-conserving pseudopotentials). Two types of unit cells containing n{sub c}=4-28 carbon atoms are considered. Results show that stability of graphene increases with increasing size of the unit cell. Energy, atomic charges, and phonon frequencies all converge above n{sub c}=24 for all functional-pseudopotentials used. Except for the LDA-GTH calculations, application of an electric field of 0.4 and 0.9 V/nm strengths does not change the trends with the size of the unit cell but instead slightly decreases the binding energy of graphene. Results of this study show that the choice of unit cell size and type is critical for calculation of reliable characteristics of graphene.

24 CFR 245.417 - Initial submission of materials to HUD: Conversion of residential units to a nonresidential use...

Science.gov (United States)

2010-04-01

... HUD: Conversion of residential units to a nonresidential use, or to cooperative housing or... Covered Action § 245.417 Initial submission of materials to HUD: Conversion of residential units to a nonresidential use, or to cooperative housing or condominiums. In the case of a conversion of residential units...

Future use of mitocans against tumour-initiating cells?

Czech Academy of Sciences Publication Activity Database

Morrison, B.J.; Anděra, Ladislav; Reynolds, B.A.; Ralph, S.J.; Neužil, Jiří

2009-01-01

Roč. 53, č. 1 (2009), s. 147-153 ISSN 1613-4125 Institutional research plan: CEZ:AV0Z50520514; CEZ:AV0Z50520701 Keywords : mitocans * tumour-initiating cells * metastasis Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.356, year: 2009

Distributed Initial Synchronization for 5G small cells

DEFF Research Database (Denmark)

Berardinelli, Gilberto; Tavares, Fernando Menezes Leitão; Tirkkonen, Olav

2014-01-01

Time synchronization in a large network of small cells enables efficient interference management as well as advanced transmission techniques which can boost the network throughput. In this paper, we focus on the distributed initial synchronization problem and propose different solutions aiming at...

Smoking initiation among young adults in the United States and Canada, 1998-2010: a systematic review.

Science.gov (United States)

Freedman, Kit S; Nelson, Nanette M; Feldman, Laura L

2012-01-01

Young adults have the highest smoking rate of any age group in the United States and Canada, and recent data indicate that they often initiate smoking as young adults. The objective of this study was to systematically review peer-reviewed articles on cigarette smoking initiation and effective prevention efforts among young adults. We searched 5 databases for research articles published in English between 1998 and 2010 on smoking initiation among young adults (aged 18-25) living in the United States or Canada. We extracted the following data from each study selected: the measure of initiation used, age range of initiation, age range of study population, data source, target population, sampling method, and sample size. We summarized the primary findings of each study according to 3 research questions and categories of data (eg, sociodemographic) that emerged during the data extraction process. Of 1,072 identified studies, we found 27 articles that met our search criteria, but several included a larger age range of initiation (eg, 18-30, 18-36) than we initially intended to include. Disparities in young adult smoking initiation existed according to sex, race, and educational attainment. The use of alcohol and illegal drugs was associated with smoking initiation. The risk of smoking initiation among young adults increased under the following circumstances: exposure to smoking, boredom or stress while serving in the military, attending tobacco-sponsored social events while in college, and exposure to social norms and perceptions that encourage smoking. Effective prevention efforts include exposure to counter-marketing, denormalization campaigns, taxation, and the presence of smoke-free policies. Much remains to be learned about young adult smoking initiation, particularly among young adults in the straight-to-work population. Dissimilar measures of smoking initiation limit our knowledge about smoking initiation among young adults. We recommend developing a standardized

Initial evaluation of children admitted on the Paediatric Intensive Care Unit

Directory of Open Access Journals (Sweden)

Esperanza Arce Delgado

2007-09-01

Full Text Available The initial evaluation of the child, when admitted on the Paediatric Intensive Unit, is a essential tool and key piece as a starting point on the development of a specific Care Plan for each child. Therefore, it is necessary the existence of a protocol, according to a rigorous methodology, so that cares will have quality and thus, it will be avoided that each nursing professional will act in a different way, according to his intuition, beliefs or improvisation capacity.The initial evaluation of the child will allow us not only to coordinate the interventions, but also to give continuity to the cares.The initial evaluation of the child document is a nursing register that is part of the clinical register of the paediatric patient. Nursing registers turn to be the best approximation of what nowadays is our job’s practice, and they are, therefore, necessary for us to be judged by a professional perspective and to make it possible to classify the services we carry out to the society.

The potential role of ribosomal protein S5 on cell cycle arrest and initiation of murine erythroleukemia cell differentiation.

Science.gov (United States)

Matragkou, Christina N; Papachristou, Eleni T; Tezias, Sotirios S; Tsiftsoglou, Asterios S; Choli-Papadopoulou, Theodora; Vizirianakis, Ioannis S

2008-07-01

Evidence now exists to indicate that some ribosomal proteins besides being structural components of the ribosomal subunits are involved in the regulation of cell differentiation and apoptosis. As we have shown earlier, initiation of erythroid differentiation of murine erythroleukemia (MEL) cells is associated with transcriptional inactivation of genes encoding ribosomal RNAs and ribosomal proteins S5 (RPS5) and L35a. In this study, we extended these observations and investigated whether transfection of MEL cells with RPS5 cDNA affects the onset of initiation of erythroid maturation and their entrance in cell cycle arrest. Stably transfected MEL cloned cells (MEL-C14 and MEL-C56) were established and assessed for their capacity to produce RPS5 RNA transcript and its translated product. The impact of RPS5 cDNA transfection on the RPS5 gene expression patterns and the accumulation of RPS5 protein in inducible transfected MEL cells were correlated with their ability to: (a) initiate differentiation, (b) enter cell cycle arrest at G(1)/G(0) phase, and (c) modulate the level of cyclin-dependent kinases CDK2, CDK4, and CDK6. The data presented indicate that deregulation of RPS5 gene expression (constitutive expression) affects RPS5 protein level and delays both the onset of initiation of erythroid maturation and entrance in cell cycle arrest in inducer-treated MEL cells. 2008 Wiley-Liss, Inc.

Healthy hospital food initiatives in the United States: time to ban sugar sweetened beverages to reduce childhood obesity

OpenAIRE

Wojcicki, Janet M

2013-01-01

While childhood obesity is a global problem, the extent and severity of the problem in United States, has resulted in a number of new initiatives, including recent hospital initiatives to limit the sale of sweetened beverages and other high calorie drinks in hospital vending machines and cafeterias. These proposed policy changes are not unique to United States, but are more comprehensive in the number of proposed hospitals that they will impact. Meanwhile, however, it is advised, that these i...

Heat balance calculation and feasibility analysis for initial startup of Fuqing nuclear turbine unit with non-nuclear steam

International Nuclear Information System (INIS)

He Liu; Xiao Bo; Song Yumeng

2014-01-01

Non-nuclear steam run up compared with nuclear steam run up, can verify the design, manufacture, installation quality of the unit, at the same time shorten the follow-up duration of the entire group ready to start debugging time. In this paper, starting from the first law of thermodynamics, Analyzed Heat balance Calculation and Feasibility analysis for Initial startup of Fuqing nuclear Turbine unit with Non-nuclear steam, By the above calculation, to the system requirements and device status on the basis of technical specifications, confirmed the feasibility of Non-nuclear steam running up in theory. After the implementation of the Non-nuclear turn of Fuqing unit, confirmed the results fit with the actual process. In summary, the Initial startup of Fuqing turbine unit with Non-nuclear steam is feasible. (authors)

Frequency distribution of the reduced unit cells of centred lattices from the Protein Data Bank.

Science.gov (United States)

Swaminathan, Kunchithapadam

2012-03-01

In crystallography, a centred conventional lattice unit cell has its corresponding reduced primitive unit cell. This study presents the frequency distribution of the reduced unit cells of all centred lattice entries of the Protein Data Bank (as of 23 August 2011) in four unit-cell-dimension-based groups and seven interaxial-angle-based subgroups. This frequency distribution is an added layer of support during space-group assignment in new crystals. In addition, some interesting patterns of distribution are discussed as well as how some reduced unit cells could be wrongly accepted as primitive lattices in a different crystal system.

Altered characteristics of cancer stem/initiating cells in a breast cancer cell line treated with persistent 5-FU chemotherapy

OpenAIRE

LÜ, XINQUAN; DENG, QING; LI, HUIXIANG; SUO, ZHENHE

2011-01-01

Drug resistance of cancer stem/initiating cells has been considered to be one of the main reasons for tumor relapse. However, knowledge concerning the changes in stem/ initiating cells during chemotherapy is limited. In the present study, the breast cancer cell line MDA-MB-468 was cultured with 5-fluorouracil and serially passaged. Six cell generations were collected. Semi-quantitative RT-PCR and flow cytometric techniques were used to evaluate the protein and mRNA expression of stem/initiati...

Targeting sarcoma tumor-initiating cells through differentiation therapy

Directory of Open Access Journals (Sweden)

Dan Han

2017-05-01

Full Text Available Human leukocyte antigen class I (HLA-I down-regulation has been reported in many human cancers to be associated with poor clinical outcome. However, its connection to tumor-initiating cells (TICs remains unknown. In this study, we report that HLA-I is down-regulated in a subpopulation of cells that have high tumor initiating capacity in different types of human sarcomas. Detailed characterization revealed their distinct molecular profiles regarding proliferation, apoptosis and stemness programs. Notably, these TICs can be induced to differentiate along distinct mesenchymal lineages, including the osteogenic pathway. The retinoic acid receptor signaling pathway is overexpressed in HLA-1 negative TICs. All-trans retinoic acid treatment successfully induced osteogenic differentiation of this subpopulation, in vitro and in vivo, resulting in significantly decreased tumor formation. Thus, our findings indicate down-regulated HLA-I is a shared feature of TICs in a variety of human sarcomas, and differentiation therapy strategies may specifically target undifferentiated TICs and inhibit tumor formation.

Smoking Initiation Among Young Adults in the United States and Canada, 1998-2010: A Systematic Review

OpenAIRE

Freedman, Kit S.; Nelson, Nanette M.; Feldman, Laura L.

2011-01-01

Introduction Young adults have the highest smoking rate of any age group in the United States and Canada, and recent data indicate that they often initiate smoking as young adults. The objective of this study was to systematically review peer-reviewed articles on cigarette smoking initiation and effective prevention efforts among young adults. Methods We searched 5 databases for research articles published in English between 1998 and 2010 on smoking initiation among young adults (aged 18-25) ...

Oncogenic KRAS activates an embryonic stem cell-like program in human colon cancer initiation.

Science.gov (United States)

Le Rolle, Anne-France; Chiu, Thang K; Zeng, Zhaoshi; Shia, Jinru; Weiser, Martin R; Paty, Philip B; Chiu, Vi K

2016-01-19

Colorectal cancer is the third most frequently diagnosed cancer worldwide. Prevention of colorectal cancer initiation represents the most effective overall strategy to reduce its associated morbidity and mortality. Activating KRAS mutation (KRASmut) is the most prevalent oncogenic driver in colorectal cancer development, and KRASmut inhibition represents an unmet clinical need. We apply a systems-level approach to study the impact of KRASmut on stem cell signaling during human colon cancer initiation by performing gene set enrichment analysis on gene expression from human colon tissues. We find that KRASmut imposes the embryonic stem cell-like program during human colon cancer initiation from colon adenoma to stage I carcinoma. Expression of miR145, an embryonic SC program inhibitor, promotes cell lineage differentiation marker expression in KRASmut colon cancer cells and significantly suppresses their tumorigenicity. Our data support an in vivo plasticity model of human colon cancer initiation that merges the intrinsic stem cell properties of aberrant colon stem cells with the embryonic stem cell-like program induced by KRASmut to optimize malignant transformation. Inhibition of the embryonic SC-like program in KRASmut colon cancer cells reveals a novel therapeutic strategy to programmatically inhibit KRASmut tumors and prevent colon cancer.

Rhombicuboctahedron unit cell based scaffolds for bone regeneration: geometry optimization with a mechanobiology - driven algorithm.

Science.gov (United States)

Boccaccio, Antonio; Fiorentino, Michele; Uva, Antonio E; Laghetti, Luca N; Monno, Giuseppe

2018-02-01

In a context more and more oriented towards customized medical solutions, we propose a mechanobiology-driven algorithm to determine the optimal geometry of scaffolds for bone regeneration that is the most suited to specific boundary and loading conditions. In spite of the huge number of articles investigating different unit cells for porous biomaterials, no studies are reported in the literature that optimize the geometric parameters of such unit cells based on mechanobiological criteria. Parametric finite element models of scaffolds with rhombicuboctahedron unit cell were developed and incorporated into an optimization algorithm that combines them with a computational mechanobiological model. The algorithm perturbs iteratively the geometry of the unit cell until the best scaffold geometry is identified, i.e. the geometry that allows to maximize the formation of bone. Performances of scaffolds with rhombicuboctahedron unit cell were compared with those of other scaffolds with hexahedron unit cells. We found that scaffolds with rhombicuboctahedron unit cell are particularly suited for supporting medium-low loads, while, for higher loads, scaffolds with hexahedron unit cells are preferable. The proposed algorithm can guide the orthopaedic/surgeon in the choice of the best scaffold to be implanted in a patient-specific anatomic region. Copyright © 2017 Elsevier B.V. All rights reserved.

International cooperative initiatives and the United Nations Framework Convention on Climate Change

DEFF Research Database (Denmark)

Bakhtiari, Fatemeh

2017-01-01

International cooperative initiatives (ICIs) are multi-country, multi-actor non-state actions that have the potential to reduce emissions of greenhouse gases. The article summarizes the literature on estimates of emission reduction potentials attributed to ICIs. This summary highlights three key ...... efforts under the UNFCCC is uncertain, but believed to be quite large. •The UNFCCC is arguably ill suited to coordinate and strengthen the accountability of international cooperative initiatives.......International cooperative initiatives (ICIs) are multi-country, multi-actor non-state actions that have the potential to reduce emissions of greenhouse gases. The article summarizes the literature on estimates of emission reduction potentials attributed to ICIs. This summary highlights three key...... transparent performance monitoring and reporting mechanisms. The article concludes with two considerations. Firstly, it advocates for the United Nations Environment Programme as one entity that could bring much-needed coordination among ICIs, and between ICIs and national government-led efforts to mitigate...

An Initiating-Event Analysis for PSA of Hanul Units 3 and 4: Results and Insights

International Nuclear Information System (INIS)

Kim, Dong-San; Park, Jin Hee

2015-01-01

As a part of the PSA, an initiating-event (IE) analysis was newly performed by considering the current state of knowledge and the requirements of the ASME/ANS probabilistic risk assessment (PRA) standard related to IE analysis. This paper describes the methods of, results and some insights from the IE analysis for the PSA of the Hanul units 3 and 4. In this study, as a part of the PSA for the Hanul units 3 and 4, an initiating-event (IE) analysis was newly performed by considering the current state of knowledge and the requirements of the ASME/ANS probabilistic risk assessment (PRA) standard. In comparison with the previous IE analysis, this study performed a more systematic and detailed analysis to identify potential initiating events, and calculated the IE frequencies by using the state-of-the-art methods and the latest data. As a result, not a few IE frequencies are quite different from the previous frequencies, which can change the major accident sequences obtained from the quantification of the PSA model

ER stress inducer tunicamycin suppresses the self-renewal of glioma-initiating cell partly through inhibiting Sox2 translation.

Science.gov (United States)

Xing, Yang; Ge, Yuqing; Liu, Chanjuan; Zhang, Xiaobiao; Jiang, Jianhai; Wei, Yuanyan

2016-06-14

Glioma-initiating cells possess tumor-initiating potential and are relatively resistant to conventional chemotherapy and irradiation. Therefore, their elimination is an essential factor for the development of efficient therapy. Here, we report that endoplasmic reticulum (ER) stress inducer tunicamycin inhibits glioma-initiating cell self-renewal as determined by neurosphere formation assay. Moreover, tunicamycin decreases the efficiency of glioma-initiating cell to initiate tumor formation. Although tunicamycin induces glioma-initiating cell apoptosis, apoptosis inhibitor z-VAD-fmk only partly abrogates the reduction in glioma-initiating cell self-renewal induced by tunicamycin. Indeed, tunicamycin reduces the expression of self-renewal regulator Sox2 at translation level. Overexpression of Sox2 obviously abrogates the reduction in glioma-initiating cell self-renewal induced by tunicamycin. Taken together, tunicamycin suppresses the self-renewal and tumorigenic potential of glioma-initiating cell partly through reducing Sox2 translation. This finding provides a cue to potential effective treatment of glioblastoma through controlling stem cells.

Canada-United States-Mexico Trilateral Cooperation on Childhood Obesity Initiative

Directory of Open Access Journals (Sweden)

Cristina Rabadán-Diehl

Full Text Available ABSTRACT Childhood obesity is an important public health problem that affects countries in the Americas. In 2014, Pan American Health Organization (PAHO Member States agreed on a Plan of Action for the Prevention of Obesity in Children and Adolescents in an effort to address the impact of this disorder in the Americas region. The interventions laid out in this regional plan are multi-faceted and require multi-sectoral partnerships. Building on a strong history of successful trilateral collaboration, Canada, Mexico, and the United States formed a partnership to address the growing epidemic of childhood obesity in the North American region. This collaborative effort, known as the Trilateral Cooperation on Childhood Obesity Initiative, is the first initiative in the region to address chronic noncommunicable diseases by bringing together technical and policy experts, with strong leadership and support from the secretaries and ministers of health. The Initiative’s goals include increasing levels of physical activity and reducing sedentary behavior through 1 increased social mobilization and citizen engagement, 2 community- based outreach, and 3 changes to the built (man-made environment. This article describes the background and development process of the Initiative; specific goals, activities, and actions achieved to date; and opportunities and next steps. This information may be useful for those forming other partnerships designed to address childhood obesity or other complex public health challenges in the region.

What cell biologists should know about the National Institutes of Health BRAIN Initiative

OpenAIRE

Insel, Thomas R.; Koroshetz, Walter

2015-01-01

The BRAIN (Brain Research through Advancing Innovative Neurotechnologies) Initiative is an ambitious project to develop innovative tools for a deeper understanding of how the brain functions in health and disease. Early programs in the National Institutes of Health BRAIN Initiative focus on tools for next-generation imaging and recording, studies of cell diversity and cell census, and integrative approaches to circuit function. In all of these efforts, cell biologists can play a leading role.

An inhibitor of K+ channels modulates human endometrial tumor-initiating cells

Directory of Open Access Journals (Sweden)

Leslie Kimberly K

2011-08-01

Full Text Available Abstract Background Many potassium ion (K+ channels function as oncogenes to sustain growth of solid tumors, but their role in cancer progression is not well understood. Emerging evidence suggests that the early progenitor cancer cell subpopulation, termed tumor initiating cells (TIC, are critical to cancer progression. Results A non-selective antagonist of multiple types of K+ channels, tetraethylammonium (TEA, was found to suppress colony formation in endometrial cancer cells via inhibition of putative TIC. The data also indicated that withdrawal of TEA results in a significant enhancement of tumorigenesis. When the TIC-enriched subpopulation was isolated from the endometrial cancer cells, TEA was also found to inhibit growth in vitro. Conclusions These studies suggest that the activity of potassium channels significantly contributes to the progression of endometrial tumors, and the antagonists of potassium channels are candidate anti-cancer drugs to specifically target tumor initiating cells in endometrial cancer therapy.

Snail1 induces epithelial-to-mesenchymal transition and tumor initiating stem cell characteristics

International Nuclear Information System (INIS)

Dang, Hien; Ding, Wei; Emerson, Dow; Rountree, C Bart

2011-01-01

Tumor initiating stem-like cells (TISCs) are a subset of neoplastic cells that possess distinct survival mechanisms and self-renewal characteristics crucial for tumor maintenance and propagation. The induction of epithelial-mesenchymal-transition (EMT) by TGFβ has been recently linked to the acquisition of TISC characteristics in breast cancer. In HCC, a TISC and EMT phenotype correlates with a worse prognosis. In this work, our aim is to elucidate the underlying mechanism by which cells acquire tumor initiating characteristics after EMT. Gene and protein expression assays and Nanog-promoter luciferase reporter were utilized in epithelial and mesenchymal phenotype liver cancer cell lines. EMT was analyzed with migration/invasion assays. TISC characteristics were analyzed with tumor-sphere self-renewal and chemotherapy resistance assays. In vivo tumor assay was performed to investigate the role of Snail1 in tumor initiation. TGFβ induced EMT in epithelial cells through the up-regulation of Snail1 in Smad-dependent signaling. Mesenchymal liver cancer post-EMT demonstrates TISC characteristics such as tumor-sphere formation but are not resistant to cytotoxic therapy. The inhibition of Snail1 in mesenchymal cells results in decreased Nanog promoter luciferase activity and loss of self-renewal characteristics in vitro. These changes confirm the direct role of Snail1 in some TISC traits. In vivo, the down-regulation of Snail1 reduced tumor growth but was not sufficient to eliminate tumor initiation. In summary, TGFβ induces EMT and TISC characteristics through Snail1 and Nanog up-regulation. In mesenchymal cells post-EMT, Snail1 directly regulates Nanog expression, and loss of Snail1 regulates tumor growth without affecting tumor initiation

Learning about the Unit Cell and Crystal Lattice with Computerized Simulations and Games: A Pilot Study

Science.gov (United States)

Luealamai, Sutha; Panijpan, Bhinyo

2012-01-01

The authors have developed a computer-based learning module on the unit cell of various types of crystal. The module has two components: the virtual unit cell (VUC) part and the subsequent unit cell hunter part. The VUC is a virtual reality simulation for students to actively arrive at the unit cell from exploring, from a broad view, the crystal…

Tumour-initiating cells vs. cancer 'stem' cells and CD133: What's in the name?

International Nuclear Information System (INIS)

Neuzil, Jiri; Stantic, Marina; Zobalova, Renata; Chladova, Jaromira; Wang, Xiufang; Prochazka, Lubomir; Dong, Lanfeng; Andera, Ladislav; Ralph, Stephen J.

2007-01-01

Recent evidence suggests that a subset of cells within a tumour have 'stem-like' characteristics. These tumour-initiating cells, distinct from non-malignant stem cells, show low proliferative rates, high self-renewing capacity, propensity to differentiate into actively proliferating tumour cells, resistance to chemotherapy or radiation, and they are often characterised by elevated expression of the stem cell surface marker CD133. Understanding the molecular biology of the CD133 + cancer cells is now essential for developing more effective cancer treatments. These may include drugs targeting organelles, such as mitochondria or lysosomes, using highly efficient and selective inducers of apoptosis. Alternatively, agents or treatment regimens that enhance sensitivity of these therapy-resistant 'tumour stem cells' to the current or emerging anti-tumour drugs would be of interest as well

Experimental and numerical studies on pressure drop in reverse electrodialysis: Effect of unit cell configuration

Energy Technology Data Exchange (ETDEWEB)

Hong, Sung Kook; Choi, Kyung Soo [Advanced Combustion Laboratory, Korea Institute of Energy Research, Daejeon (Korea, Republic of); Kim, Chan Soo; Hwang, Kyo Sik; Han, Ji Hyung; Kim, Han Ki; Jeong, Nam Jo [Jeju Global Research Center, Korea Institute of Energy Research, Jeju (Korea, Republic of)

2016-11-15

Experimental and numerical studies on pressure drop in Reverse electrodialysis (RED) were performed. In this study, a module with 200 unit cells is considered for the demonstration of bench-scale RED module and two different unit cell configurations are utilized. Pressure drop through the module is measured by varying flow rates. For evaluating the hydrodynamic characteristics in the unit cell, a numerical simulation is also conducted and the simplified method using a porous media model is employed to simulate the channel filled with spacer. Due to the insertion of spacer and narrow channel, great pressure loss occurs along the unit cell. Based on estimated pressure data, high pressure difference between seawater and fresh water channel takes place locally in the unit cell configuration with crossflow direction, leading to a leakage problem through the membrane and finally degradation in the output power. Consequently, it is confirmed that the unit cell configuration is one of the important design parameters in a RED module.

Moving the Barricades to Physical Activity: A Qualitative Analysis of Open Streets Initiatives Across the United States.

Science.gov (United States)

Eyler, Amy A; Hipp, J Aaron; Lokuta, Julie

2015-01-01

Ciclovía, or Open Streets initiatives, are events where streets are opened for physical activity and closed to motorized traffic. Although the initiatives are gaining popularity in the United States, little is known about planning and implementing them. The goals of this paper are to explore the development and implementation of Open Streets initiatives and make recommendations for increasing the capacity of organizers to enhance initiative success. Phenomenology with qualitative analysis of structured interviews was used. Study setting was urban and suburban communities in the United States. Study participants were organizers of Open Streets initiatives in U.S. cities. Using a list of 47 events held in 2011, 27 lead organizers were interviewed by telephone about planning, implementation, and lessons learned. The interviews were digitally recorded and transcribed. A phenomenologic approach was used, an initial coding tool was developed after reviewing a sample of transcripts, and constant comparative coding methodology was applied. Themes and subthemes were generated from codes. The most common reasons for initiation were to highlight or improve health and transportation. Most initiatives aimed to reach the general population, but some targeted families, children, or specific neighborhoods. Getting people to understand the concept of Open Streets was an important challenge. Other challenges included lack of funding and personnel, and complex logistics. These initiatives democratize public space for citizens while promoting physical activity, social connectedness, and other broad agendas. There are opportunities for the research community to contribute to the expanse and sustainability of Open Streets, particularly in evaluation and dissemination.

Role of tumour initiating cells in the radiation resistance of osteosarcoma

International Nuclear Information System (INIS)

Klymenko, Olena

2014-01-01

In the present study we confirm that mouse osteosarcoma (MOS) cells lines possess a subset of cells with Tumour Initiating Cells (TICs) properties. We found that isolated TICs are not inherently radioresistant compared to non-TICs. On the other hand, we found that the fraction of TICs correlates well with the radiosensitivity of MOS cell lines measured using clonogenic cell survival assay. We conclude from our study that the TICs contribute to the tumour radiation response due to their interaction with their tumour surrounding environmental (niche).

Role of tumour initiating cells in the radiation resistance of osteosarcoma

Energy Technology Data Exchange (ETDEWEB)

Klymenko, Olena

2014-02-26

In the present study we confirm that mouse osteosarcoma (MOS) cells lines possess a subset of cells with Tumour Initiating Cells (TICs) properties. We found that isolated TICs are not inherently radioresistant compared to non-TICs. On the other hand, we found that the fraction of TICs correlates well with the radiosensitivity of MOS cell lines measured using clonogenic cell survival assay. We conclude from our study that the TICs contribute to the tumour radiation response due to their interaction with their tumour surrounding environmental (niche).

Initiator of carcinogenesis selectively and stably inhibits stem cell differentiation: a concept that initiation of carcinogenesis involves multiple phases

International Nuclear Information System (INIS)

Scott, R.E.; Maercklein, P.B.

1985-01-01

A concept of carcinogenesis was recently devised in our laboratory that suggests the development of defects in the control of cell differentiation is associated with an early phase of carcinogenesis. To test this proposal directly, the effects of an initiator of carcinogenesis (i.e., UV irradiation) on proadipocyte stem cell differentiation and proliferation was assayed. In this regard, 3T3 T proadipocytes represent a nontransformed mesenchymal stem cell line that possesses the ability to regulate its differentiation at a distinct state in the G 1 phase of the cell cycle as well as the ability to regulate its proliferation at two additional G 1 states. The results establish that a slow dosage of 254 nm UV irradiation selectivity and stably inhibits the differentiation of a high percentage of proadipocyte stem cells without significantly altering their ability to regulate cellular proliferation in growth factor-deficient or nutrient-deficient culture conditions. Differentiation-defect proadipocyte stem cells are demonstrated not to be completely transformed but to show an increased spontaneous transformation rate, as evidenced by the formation of type III foci in high density cell cultures. These data support the role of defects in the control of differentiation in the inhibition of carcinogenesis. These observations support a concept that the initiation of carcinogenesis involves multiple phases

Influence of radiation on initial attachment of osteoblast-like cells on titanium plate

International Nuclear Information System (INIS)

Kakuta, Saburo; Hamazaki, Miki; Mitsumoto, Kazuyo; Itabashi, Yuto; Fujimori, Shinya; Miyazaki, Takashi; Nagumo, Masao

1996-01-01

Radiotherapy is a useful and convenient therapy for oral cancer. However, there are many side effects such as stomatitis and radionecrosis of jaws. Radionecrosis may cause loosing or infection of biomaterials used for reconstruction of jaws. In this experiment, in vitro investigation was performed to clarify the influence of radiation on initial attachment of osteoblast-like cells to the titanium plate. UMR-106 and MC3T3-E1 cells were used as osteoblast-like cells. Cell attachment was evaluated by alkaline phosphatase activity and staining attached cells with crystal violet. The results revealed that initial attachment of osteoblast-like cells to the titanium plate was dose-dependently decreased by radiation and that radiosensitivity of each cell was different respectively. Furthermore, the participation of active oxygen was suggested because of partial recovery of cell attachment by addition of superoxide dismutase and/or an antioxidant such as ascorbic acid. (author)

Polymer coating comprising 2-methoxyethyl acrylate units synthesized by surface-initiated atom transfer radical polymerization

DEFF Research Database (Denmark)

2011-01-01

Source: US2012184029A The present invention relates to preparation of a polymer coating comprising or consisting of polymer chains comprising or consisting of units of 2-methoxyethyl acrylate synthesized by Surface-Initiated Atom Transfer Radical Polymerization (SI ATRP) such as ARGET SI ATRP...

Hybrid clone cells derived from human breast epithelial cells and human breast cancer cells exhibit properties of cancer stem/initiating cells.

Science.gov (United States)

Gauck, Daria; Keil, Silvia; Niggemann, Bernd; Zänker, Kurt S; Dittmar, Thomas

2017-08-02

The biological phenomenon of cell fusion has been associated with cancer progression since it was determined that normal cell × tumor cell fusion-derived hybrid cells could exhibit novel properties, such as enhanced metastatogenic capacity or increased drug resistance, and even as a mechanism that could give rise to cancer stem/initiating cells (CS/ICs). CS/ICs have been proposed as cancer cells that exhibit stem cell properties, including the ability to (re)initiate tumor growth. Five M13HS hybrid clone cells, which originated from spontaneous cell fusion events between M13SV1-EGFP-Neo human breast epithelial cells and HS578T-Hyg human breast cancer cells, and their parental cells were analyzed for expression of stemness and EMT-related marker proteins by Western blot analysis and confocal laser scanning microscopy. The frequency of ALDH1-positive cells was determined by flow cytometry using AldeRed fluorescent dye. Concurrently, the cells' colony forming capabilities as well as the cells' abilities to form mammospheres were investigated. The migratory activity of the cells was analyzed using a 3D collagen matrix migration assay. M13HS hybrid clone cells co-expressed SOX9, SLUG, CK8 and CK14, which were differently expressed in parental cells. A variation in the ALDH1-positive putative stem cell population was observed among the five hybrids ranging from 1.44% (M13HS-7) to 13.68% (M13HS-2). In comparison to the parental cells, all five hybrid clone cells possessed increased but also unique colony formation and mammosphere formation capabilities. M13HS-4 hybrid clone cells exhibited the highest colony formation capacity and second highest mammosphere formation capacity of all hybrids, whereby the mean diameter of the mammospheres was comparable to the parental cells. In contrast, the largest mammospheres originated from the M13HS-2 hybrid clone cells, whereas these cells' mammosphere formation capacity was comparable to the parental breast cancer cells. All M13HS

Acetate is a superior substrate for microbial fuel cell initiation preceding bioethanol effluent utilization

DEFF Research Database (Denmark)

Sun, Guotao; Thygesen, Anders; Meyer, Anne S.

2015-01-01

resistance. The BE mainly contained 20.5 g/L xylose, 1.8 g/Larabinose, and 2.5 g/L propionic acid. The MFCs initially fedwith acetate showed shorter initiation time (1 day), higheraverage cell voltage (634±9 mV), and higher coulombic efficiency(31.5±0.5 %) than those initially fed with ace/xyl orxylose....... However, BE-initiated MFCs only generated 162±1 mV. The acetate-initiated MFCs exhibited longer adaptation time (21 h) and lower cell voltage (645±10 mV) when the substrate was switched to xylose, whereas substrate switching to BE produced the highest voltage (656 mV), maximumpower density (362±27 mW/m2...

Tumor-Initiating Label-Retaining Cancer Cells in Human Gastrointestinal Cancers Undergo Asymmetric Cell Division

Science.gov (United States)

Xin, Hong-Wu; Hari, Danielle M.; Mullinax, John E.; Ambe, Chenwi M.; Koizumi, Tomotake; Ray, Satyajit; Anderson, Andrew J.; Wiegand, Gordon W.; Garfield, Susan H.; Thorgeirsson, Snorri S.; Avital, Itzhak

2012-01-01

Label-retaining cells (LRCs) have been proposed to represent adult tissue stem cells. LRCs are hypothesized to result from either slow cycling or asymmetric cell division (ACD). However, the stem cell nature and whether LRC undergo ACD remain controversial. Here, we demonstrate label-retaining cancer cells (LRCCs) in several gastrointestinal (GI) cancers including fresh surgical specimens. Using a novel method for isolation of live LRCC, we demonstrate that a subpopulation of LRCC is actively dividing and exhibits stem cells and pluripotency gene expression profiles. Using real-time confocal microscopic cinematography, we show live LRCC undergoing asymmetric nonrandom chromosomal cosegregation LRC division. Importantly, LRCCs have greater tumor-initiating capacity than non-LRCCs. Based on our data and that cancers develop in tissues that harbor normal-LRC, we propose that LRCC might represent a novel population of GI stem-like cancer cells. LRCC may provide novel mechanistic insights into the biology of cancer and regenerative medicine and present novel targets for cancer treatment. PMID:22331764

Additively Manufactured Open-Cell Porous Biomaterials Made from Six Different Space-Filling Unit Cells: The Mechanical and Morphological Properties

Directory of Open Access Journals (Sweden)

Seyed Mohammad Ahmadi

2015-04-01

Full Text Available It is known that the mechanical properties of bone-mimicking porous biomaterials are a function of the morphological properties of the porous structure, including the configuration and size of the repeating unit cell from which they are made. However, the literature on this topic is limited, primarily because of the challenge in fabricating porous biomaterials with arbitrarily complex morphological designs. In the present work, we studied the relationship between relative density (RD of porous Ti6Al4V EFI alloy and five compressive properties of the material, namely elastic gradient or modulus (Es20–70, first maximum stress, plateau stress, yield stress, and energy absorption. Porous structures with different RD and six different unit cell configurations (cubic (C, diamond (D, truncated cube (TC, truncated cuboctahedron (TCO, rhombic dodecahedron (RD, and rhombicuboctahedron (RCO were fabricated using selective laser melting. Each of the compressive properties increased with increase in RD, the relationship being of a power law type. Clear trends were seen in the influence of unit cell configuration and porosity on each of the compressive properties. For example, in terms of Es20–70, the structures may be divided into two groups: those that are stiff (comprising those made using C, TC, TCO, and RCO unit cell and those that are compliant (comprising those made using D and RD unit cell.

Report on the Trilateral Initiative. IAEA verification of weapon-origin material in the Russian Federation and the United States

International Nuclear Information System (INIS)

Shea, Thomas E.

2001-01-01

Just over five years ago, the Trilateral Initiative was launched to investigate the technical, legal and financial issues associated with IAEA verification of weapon-origin fissile material in the Russian Federation and the United States. Since then, the Joint Working Group has developed concepts and equipment suitable for such a verification mission, anticipating that the States would submit classified forms of fissile material to IAEA verification under new agreements developed for this purpose. This article summarizes the accomplishments to date and identifies the future steps foreseen under the Trilateral Initiative. As there is no legal commitment on the Parties to this Initiative as yet, the issues considered are still changing. Since it was launched, the Initiative has been given a sense of importance and weight, raising the expectations of the international community. The Final Document of the 2000 Conference on the Treaty on the Non-Proliferation of Nuclear Weapons (NPT), for example, under the review of Article VI of the Treaty, includes the statement to 'complete and implement the Trilateral Initiative'. It was launched following independent statements by the President of the United States beginning in 1993, and by the President of the Russian Federation in 1996. It is an Initiative between the IAEA, the Russian Federation and the United States that is in the context of Article VI of the NPT. The intention is to examine the technical, legal and financial issues associated with IAEA verification of weapon origin and other fissile material released from defense programmes in those two countries

The initial growth of complex oxides : study and manipulation

NARCIS (Netherlands)

Rijnders, Augustinus J.H.M.

2001-01-01

In this thesis, the initial growth stage, i.e., nucleation and growth of the first few unit cell layers, of complex oxides was studied in real time during pulsed laser deposition (PLD). These studies were performed at their optimal epitaxial growth conditions, i.e., high temperature and high oxygen

40 CFR Table 33 to Subpart Uuu of... - Initial Compliance With HAP Emission Limits for Sulfur Recovery Units

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 12 2010-07-01 2010-07-01 true Initial Compliance With HAP Emission Limits for Sulfur Recovery Units 33 Table 33 to Subpart UUU of Part 63 Protection of Environment..., Subpt. UUU, Table 33 Table 33 to Subpart UUU of Part 63—Initial Compliance With HAP Emission Limits for...

Mitochondria: An intriguing target for killing tumour-initiating cells

Czech Academy of Sciences Publication Activity Database

Yan, B.; Dong, L.; Neužil, Jiří

2016-01-01

Roč. 26, JAN 2016 (2016), s. 86-93 ISSN 1567-7249 R&D Projects: GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:86652036 Keywords : Tumour-initiating cells * ALPHA-TOCOPHERYL SUCCINATE * Therapeutic resistance * Mitochondria Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.704, year: 2016

Empirical Derivation of Correction Factors for Human Spiral Ganglion Cell Nucleus and Nucleolus Count Units.

Science.gov (United States)

Robert, Mark E; Linthicum, Fred H

2016-01-01

Profile count method for estimating cell number in sectioned tissue applies a correction factor for double count (resulting from transection during sectioning) of count units selected to represent the cell. For human spiral ganglion cell counts, we attempted to address apparent confusion between published correction factors for nucleus and nucleolus count units that are identical despite the role of count unit diameter in a commonly used correction factor formula. We examined a portion of human cochlea to empirically derive correction factors for the 2 count units, using 3-dimensional reconstruction software to identify double counts. The Neurotology and House Histological Temporal Bone Laboratory at University of California at Los Angeles. Using a fully sectioned and stained human temporal bone, we identified and generated digital images of sections of the modiolar region of the lower first turn of cochlea, identified count units with a light microscope, labeled them on corresponding digital sections, and used 3-dimensional reconstruction software to identify double-counted count units. For 25 consecutive sections, we determined that double-count correction factors for nucleus count unit (0.91) and nucleolus count unit (0.92) matched the published factors. We discovered that nuclei and, therefore, spiral ganglion cells were undercounted by 6.3% when using nucleolus count units. We determined that correction factors for count units must include an element for undercounting spiral ganglion cells as well as the double-count element. We recommend a correction factor of 0.91 for the nucleus count unit and 0.98 for the nucleolus count unit when using 20-µm sections. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2015.

Earlier defibrotide initiation post-diagnosis of veno-occlusive disease/sinusoidal obstruction syndrome improves Day +100 survival following haematopoietic stem cell transplantation.

Science.gov (United States)

Richardson, Paul G; Smith, Angela R; Triplett, Brandon M; Kernan, Nancy A; Grupp, Stephan A; Antin, Joseph H; Lehmann, Leslie; Miloslavsky, Maja; Hume, Robin; Hannah, Alison L; Nejadnik, Bijan; Soiffer, Robert J

2017-07-01

Hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a progressive, potentially fatal complication of conditioning for haematopoietic stem cell transplant (HSCT). The VOD/SOS pathophysiological cascade involves endothelial-cell activation and damage, and a prothrombotic-hypofibrinolytic state. Severe VOD/SOS (typically characterized by multi-organ dysfunction) may be associated with >80% mortality. Defibrotide is approved for treating severe hepatic VOD/SOS post-HSCT in the European Union, and for hepatic VOD/SOS with renal or pulmonary dysfunction post-HSCT in the United States. Previously, defibrotide (25 mg/kg/day in 4 divided doses for a recommended ≥21 days) was available through an expanded-access treatment protocol for patients with VOD/SOS. Data from this study were examined post-hoc to determine if the timing of defibrotide initiation post-VOD/SOS diagnosis affected Day +100 survival post-HSCT. Among 573 patients, defibrotide was started on the day of VOD/SOS diagnosis in approximately 30%, and within 7 days in >90%. The relationship between Day +100 survival and treatment initiation before/after specific days post-diagnosis showed superior survival when treatment was initiated closer to VOD/SOS diagnosis with a statistically significant trend over time for better outcomes with earlier treatment initiation (P defibrotide should not be delayed after diagnosis of VOD/SOS. © 2017 The Authors. British Journal of Haematology published by John Wiley & Sons Ltd.

Graphics processing units accelerated semiclassical initial value representation molecular dynamics

Energy Technology Data Exchange (ETDEWEB)

Tamascelli, Dario; Dambrosio, Francesco Saverio [Dipartimento di Fisica, Università degli Studi di Milano, via Celoria 16, 20133 Milano (Italy); Conte, Riccardo [Department of Chemistry and Cherry L. Emerson Center for Scientific Computation, Emory University, Atlanta, Georgia 30322 (United States); Ceotto, Michele, E-mail: michele.ceotto@unimi.it [Dipartimento di Chimica, Università degli Studi di Milano, via Golgi 19, 20133 Milano (Italy)

2014-05-07

This paper presents a Graphics Processing Units (GPUs) implementation of the Semiclassical Initial Value Representation (SC-IVR) propagator for vibrational molecular spectroscopy calculations. The time-averaging formulation of the SC-IVR for power spectrum calculations is employed. Details about the GPU implementation of the semiclassical code are provided. Four molecules with an increasing number of atoms are considered and the GPU-calculated vibrational frequencies perfectly match the benchmark values. The computational time scaling of two GPUs (NVIDIA Tesla C2075 and Kepler K20), respectively, versus two CPUs (Intel Core i5 and Intel Xeon E5-2687W) and the critical issues related to the GPU implementation are discussed. The resulting reduction in computational time and power consumption is significant and semiclassical GPU calculations are shown to be environment friendly.

CD133 expression is not restricted to stem cells, and both CD133+ and CD133– metastatic colon cancer cells initiate tumors

Science.gov (United States)

Shmelkov, Sergey V.; Butler, Jason M.; Hooper, Andrea T.; Hormigo, Adilia; Kushner, Jared; Milde, Till; St. Clair, Ryan; Baljevic, Muhamed; White, Ian; Jin, David K.; Chadburn, Amy; Murphy, Andrew J.; Valenzuela, David M.; Gale, Nicholas W.; Thurston, Gavin; Yancopoulos, George D.; D’Angelica, Michael; Kemeny, Nancy; Lyden, David; Rafii, Shahin

2008-01-01

Colon cancer stem cells are believed to originate from a rare population of putative CD133+ intestinal stem cells. Recent publications suggest that a small subset of colon cancer cells expresses CD133, and that only these CD133+ cancer cells are capable of tumor initiation. However, the precise contribution of CD133+ tumor-initiating cells in mediating colon cancer metastasis remains unknown. Therefore, to temporally and spatially track the expression of CD133 in adult mice and during tumorigenesis, we generated a knockin lacZ reporter mouse (CD133lacZ/+), in which the expression of lacZ is driven by the endogenous CD133 promoters. Using this model and immunostaining, we discovered that CD133 expression in colon is not restricted to stem cells; on the contrary, CD133 is ubiquitously expressed on differentiated colonic epithelium in both adult mice and humans. Using Il10–/–CD133lacZ mice, in which chronic inflammation in colon leads to adenocarcinomas, we demonstrated that CD133 is expressed on a full gamut of colonic tumor cells, which express epithelial cell adhesion molecule (EpCAM). Similarly, CD133 is widely expressed by human primary colon cancer epithelial cells, whereas the CD133– population is composed mostly of stromal and inflammatory cells. Conversely, CD133 expression does not identify the entire population of epithelial and tumor-initiating cells in human metastatic colon cancer. Indeed, both CD133+ and CD133– metastatic tumor subpopulations formed colonospheres in in vitro cultures and were capable of long-term tumorigenesis in a NOD/SCID serial xenotransplantation model. Moreover, metastatic CD133– cells form more aggressive tumors and express typical phenotypic markers of cancer-initiating cells, including CD44 (CD44+CD24–), whereas the CD133+ fraction is composed of CD44lowCD24+ cells. Collectively, our data suggest that CD133 expression is not restricted to intestinal stem or cancer-initiating cells, and during the metastatic

Tumour-initiating cells vs. cancer "stem" cells and CD133: What's in the name?

Czech Academy of Sciences Publication Activity Database

Neužil, Jiří; Stantic, M.; Zobalová, Renata; Chladová, Jaromíra; Wang, X. F.; Procházka, L.; Dong, L.; Anděra, Ladislav; Ralph, S.J.

2007-01-01

Roč. 255, č. 4 (2007), s. 855-859 ISSN 0006-291X Institutional research plan: CEZ:AV0Z50520514; CEZ:AV0Z50520701 Keywords : tumour-initiating cells * CD133 * resistance to treatment Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.749, year: 2007

Properties of internalization factors contributing to the uptake of extracellular DNA into tumor-initiating stem cells of mouse Krebs-2 cell line.

Science.gov (United States)

Dolgova, Evgeniya V; Potter, Ekaterina A; Proskurina, Anastasiya S; Minkevich, Alexandra M; Chernych, Elena R; Ostanin, Alexandr A; Efremov, Yaroslav R; Bayborodin, Sergey I; Nikolin, Valeriy P; Popova, Nelly A; Kolchanov, Nikolay A; Bogachev, Sergey S

2016-05-25

Previously, we demonstrated that poorly differentiated cells of various origins, including tumor-initiating stem cells present in the ascites form of mouse cancer cell line Krebs-2, are capable of naturally internalizing both linear double-stranded DNA and circular plasmid DNA. The method of co-incubating Krebs-2 cells with extracellular plasmid DNA (pUC19) or TAMRA-5'-dUTP-labeled polymerase chain reaction (PCR) product was used. It was found that internalized plasmid DNA isolated from Krebs-2 can be transformed into competent Escherichia coli cells. Thus, the internalization processes taking place in the Krebs-2 cell subpopulation have been analyzed and compared, as assayed by E. coli colony formation assay (plasmid DNA) and cytofluorescence (TAMRA-DNA). We showed that extracellular DNA both in the form of plasmid DNA and a PCR product is internalized by the same subpopulation of Krebs-2 cells. We found that the saturation threshold for Krebs-2 ascites cells is 0.5 μg DNA/10(6) cells. Supercoiled plasmid DNA, human high-molecular weight DNA, and 500 bp PCR fragments are internalized into the Krebs-2 tumor-initiating stem cells via distinct, non-competing internalization pathways. Under our experimental conditions, each cell may harbor 340-2600 copies of intact plasmid material, or up to 3.097 ± 0.044×10(6) plasmid copies (intact or not), as detected by quantitative PCR. The internalization dynamics of extracellular DNA, copy number of the plasmids taken up by the cells, and competition between different types of double-stranded DNA upon internalization into tumor-initiating stem cells of mouse ascites Krebs-2 have been comprehensively analyzed. Investigation of the extracellular DNA internalization into tumor-initiating stem cells is an important part of understanding their properties and possible destruction mechanisms. For example, a TAMRA-labeled DNA probe may serve as an instrument to develop a target for the therapy of cancer, aiming at elimination of

Plasma-activated medium (PAM) kills human cancer-initiating cells.

Science.gov (United States)

Ikeda, Jun-Ichiro; Tanaka, Hiromasa; Ishikawa, Kenji; Sakakita, Hajime; Ikehara, Yuzuru; Hori, Masaru

2018-01-01

Medical non-thermal plasma (NTP) treatments for various types of cancers have been reported. Cells with tumorigenic potential (cancer-initiating cells; CICs) are few in number in many types of tumors. CICs efficiently eliminate anti-cancer chemicals and exhibit high-level aldehyde dehydrogenase (ALDH) activity. We previously examined the effects of direct irradiation via NTP on cancer cells; even though we targeted CICs expressing high levels of ALDH, such treatment affected both non-CICs and CICs. Recent studies have shown that plasma-activated medium (PAM) (culture medium irradiated by NTP) selectively induces apoptotic death of cancer but not normal cells. Therefore, we explored the anti-cancer effects of PAM on CICs among endometrioid carcinoma and gastric cancer cells. PAM reduced the viability of cells expressing both low and high levels of ALDH. Combined PAM/cisplatin appeared to kill cancer cells more efficiently than did PAM or cisplatin alone. In a mouse tumor xenograft model, PAM exerted an anti-cancer effect on CICs. Thus, our results suggest that PAM effectively kills both non-CICs and CICs, as does NTP. Therefore, PAM may be a useful new anti-cancer therapy, targeting various cancer cells including CICs. © 2017 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.

Polymer electrolyte fuel cell mini power unit for portable application

Energy Technology Data Exchange (ETDEWEB)

Urbani, F.; Squadrito, G.; Barbera, O.; Giacoppo, G.; Passalacqua, E. [CNR-ITAE, via Salita S. Lucia sopra Contesse n. 5, 98126 S. Lucia, Messina (Italy); Zerbinati, O. [Universita del Piemonte Orientale, Dip. di Scienze dell' Ambiente e della Vita, via Bellini 25/g, 15100 Alessandria (Italy)

2007-06-20

This paper describes the design, realisation and test of a power unit based on a polymer electrolyte fuel cell, operating at room temperature, for portable application. The device is composed of an home made air breathing fuel cell stack, a metal hydride tank for H{sub 2} supply, a dc-dc converter for power output control and a fan for stack cooling. The stack is composed by 10 cells with an active surface of 25 cm{sup 2} and produces a rated power of 15 W at 6 V and 2 A. The stack successfully runs with end-off fed hydrogen without appreciable performance degradation during the time. The final assembled system is able to generate 12 W at 9.5 V, and power a portable DVD player for 3 h in continuous. The power unit has collected about 100 h of operation without maintenance. (author)

Characterization of human embryonic stem cell lines by the International Stem Cell Initiative

Czech Academy of Sciences Publication Activity Database

Adewumi, O.; Aflatoonian, B.; Ahrlund-Richter, L.; Amit, M.; Andrews, P.W.; Beighton, G.; Bello, P.A.; Benvenisty, N.; Berry, L.S.; Bevan, S.; Blum, B.; Brooking, J.; Chen, K.G.; Choo, A.B.H.; Churchill, G.A.; Corbel, M.; Damjanov, I.; Draper, J.S.; Dvořák, Petr; Emanuelsson, K.; Fleck, R.A.; Ford, A.; Gertow, K.; Gertsenstein, M.; Gokhale, P.J.; Hamilton, R.S.; Hampl, Aleš; Healy, L.E.; Hovatta, O.; Hyllner, J.; Imreh, M.P.; Itskovitz-Eldor, J.; Jackson, J.; Johnson, J.L.; Jones, M.; Kee, K.; King, B.L.; Knowles, B.B.; Lako, M.; Lebrin, F.; Mallon, B.S.; Manning, D.; Mayshar, Y.; Mckay, D.G.; Michalska, A.E.; Mikkola, M.; Mileikovsky, M.; Minger, S.L.; Moore, H.D.; Mummery, Ch.L.; Nagy, A.; Nakutsuji, N.; O´Brien, C.M.; Oh, S.K.W.; Olsson, C.; Otonkoski, T.; Park, K.Y.; Passier, R.; Patel, H.; Patel, M.; Pedersen, R.; Pera, M.F.; Piekarczyk, M.S.; Pera, R.A.P.; Reubinoff, B.E.; Robins, A.J.; Rossant, J.; Rugg-Gunn, P.; Schulz, T.C.; Semb, H.; Sherrer, E.S.; Siemen, H.; Stacey, G.N.; Stojkovic, M.; Suemori, H.; Szatkiewicz, J.; Turetsky, T.; Tuuri, T.; Van den Brink, S.; Vintersten, K.; Vuoristo, S.; Ward, D.; Weaver, T.A.; Young, L.A.; Zhang, W.

2007-01-01

Roč. 25, č. 7 (2007), s. 803-816 ISSN 1087-0156 R&D Projects: GA MŠk 1M0538; GA ČR GA301/05/0463; GA ČR GA305/05/0434 Institutional research plan: CEZ:AV0Z50390512 Keywords : International Stem Cell Initiative Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 22.848, year: 2007

40 CFR Table 19 to Subpart Uuu of... - Initial Compliance With Organic HAP Emission Limits for Catalytic Reforming Units

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 12 2010-07-01 2010-07-01 true Initial Compliance With Organic HAP Emission Limits for Catalytic Reforming Units 19 Table 19 to Subpart UUU of Part 63 Protection of... HAP Emission Limits for Catalytic Reforming Units As stated in § 63.1566(b)(7), you shall meet each...

40 CFR Table 12 to Subpart Uuu of... - Initial Compliance With Organic HAP Emission Limits for Catalytic Cracking Units

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 12 2010-07-01 2010-07-01 true Initial Compliance With Organic HAP Emission Limits for Catalytic Cracking Units 12 Table 12 to Subpart UUU of Part 63 Protection of... HAP Emission Limits for Catalytic Cracking Units As stated in § 63.1565(b)(4), you shall meet each...

SOX2 regulates self-renewal and tumorigenicity of human melanoma-initiating cells.

Science.gov (United States)

Santini, R; Pietrobono, S; Pandolfi, S; Montagnani, V; D'Amico, M; Penachioni, J Y; Vinci, M C; Borgognoni, L; Stecca, B

2014-09-18

Melanoma is one of the most aggressive types of human cancer, characterized by enhanced heterogeneity and resistance to conventional therapy at advanced stages. We and others have previously shown that HEDGEHOG-GLI (HH-GLI) signaling is required for melanoma growth and for survival and expansion of melanoma-initiating cells (MICs). Recent reports indicate that HH-GLI signaling regulates a set of genes typically expressed in embryonic stem cells, including SOX2 (sex-determining region Y (SRY)-Box2). Here we address the function of SOX2 in human melanomas and MICs and its interaction with HH-GLI signaling. We find that SOX2 is highly expressed in melanoma stem cells. Knockdown of SOX2 sharply decreases self-renewal in melanoma spheres and in putative melanoma stem cells with high aldehyde dehydrogenase activity (ALDH(high)). Conversely, ectopic expression of SOX2 in melanoma cells enhances their self-renewal in vitro. SOX2 silencing also inhibits cell growth and induces apoptosis in melanoma cells. In addition, depletion of SOX2 progressively abrogates tumor growth and leads to a significant decrease in tumor-initiating capability of ALDH(high) MICs upon xenotransplantation, suggesting that SOX2 is required for tumor initiation and for continuous tumor growth. We show that SOX2 is regulated by HH signaling and that the transcription factors GLI1 and GLI2, the downstream effectors of HH-GLI signaling, bind to the proximal promoter region of SOX2 in primary melanoma cells. In functional studies, we find that SOX2 function is required for HH-induced melanoma cell growth and MIC self-renewal in vitro. Thus SOX2 is a critical factor for self-renewal and tumorigenicity of MICs and an important mediator of HH-GLI signaling in melanoma. These findings could provide the basis for novel therapeutic strategies based on the inhibition of SOX2 for the treatment of a subset of human melanomas.

T-Cell Subsets Predict Mortality in Malnourished Zambian Adults Initiating Antiretroviral Therapy.

Directory of Open Access Journals (Sweden)

Caroline C Chisenga

Full Text Available To estimate the prognostic value of T-cell subsets in Zambian patients initiating antiretroviral therapy (ART, and to assess the impact of a nutritional intervention on T-cell subsets.This was a sub-study of a randomised clinical trial of a nutritional intervention for malnourished adults initiating ART. Participants in a randomised controlled trial (NUSTART trial were enrolled between April and December 2012. Participants received lipid-based nutritional supplement either with or without additional vitamins and minerals. Immunophenotyping was undertaken at baseline and, in survivors, after 12 weeks of ART to characterize T-cell subsets using the markers CD3, CD4, CD8, CD45RA, CCR7, CD28, CD57, CD31, α4β7, Ki67, CD25 and HLA-DR. Univariate and multivariate survival analysis was performed, and responses to treatment were analysed using the Wicoxon rank-sum test.Among 181 adults, 36 (20% died by 12 weeks after starting ART. In univariate analysis, patients who died had fewer proliferating, more naïve and fewer gut homing CD4+ T-cells compared to survivors; and more senescent and fewer proliferating CD8+ T-cells. In a multivariate Cox regression model high naïve CD4+, low proliferating CD4+, high senescent CD8+ and low proliferating CD8+ subsets were independently associated with increased risk of death. Recent CD4+ thymic emigrants increased less between recruitment and 12 weeks of ART in the intervention group compared to the control group.Specific CD4+ T-cell subsets are of considerable prognostic significance for patients initiating ART in Zambia, but only thymic output responded to this nutritional intervention.

Evaluation of the impact of banking umbilical cord blood units with high cell dose for ethnically diverse patients.

Science.gov (United States)

Stritesky, Gretta; Wadsworth, Kimberly; Duffy, Merry; Buck, Kelly; Dehn, Jason

2018-02-01

Umbilical cord blood units provide an important stem cell source for transplantation, particularly for patients of ethnic diversity who may not have suitably matched available, adult-unrelated donors. However, with the cost of cord blood unit acquisition from public banks significantly higher than that for adult-unrelated donors, attention is focused on decreasing cost yet still providing cord blood units to patients in need. Historical practices of banking units with low total nucleated cell counts, including units with approximately 90 × 10 7 total nucleated cells, indicates that most banked cord blood units have much lower total nucleated cell counts than are required for transplant. The objective of this study was to determine the impact on the ability to identify suitable cord blood units for transplantation if the minimum total nucleated cell count for banking were increased from 90 × 10 7 to 124 or 149 × 10 7 . We analyzed ethnically diverse patients (median age, 3 years) who underwent transplantation of a single cord blood unit in 2005 to 2016. A cord blood unit search was evaluated to identify units with equal or greater human leukocyte antigen matching and a greater total nucleated cell count than that of the transplanted cord blood unit (the replacement cord blood unit). If the minimum total nucleated cell count for banking increased to 124 or 149 × 10 7 , then from 75 to 80% of patients would still have at least 1 replacement cord blood unit in the current (2016) cord blood unit inventory. The best replacement cord blood units were often found among cords with the same ethnic background as the patient. The current data suggest that, if the minimum total nucleated cell count were increased for banking, then it would likely lead to an inventory of more desirable cord blood units while having minimal impact on the identification of suitable cord blood units for transplantation. © 2017 AABB.

Radiosensitivity of cancer-initiating cells and normal stem cells (or what the Heisenberg uncertainly principle has to do with biology).

Science.gov (United States)

Woodward, Wendy Ann; Bristow, Robert Glen

2009-04-01

Mounting evidence suggests that parallels between normal stem cell biology and cancer biology may provide new targets for cancer therapy. Prospective identification and isolation of cancer-initiating cells from solid tumors has promoted the descriptive and functional identification of these cells allowing for characterization of their response to contemporary cancer therapies, including chemotherapy and radiation. In clinical radiation therapy, the failure to clinically eradicate all tumor cells (eg, a lack of response, partial response, or nonpermanent complete response by imaging) is considered a treatment failure. As such, biologists have explored the characteristics of the small population of clonogenic cancer cells that can survive and are capable of repopulating the tumor after subcurative therapy. Herein, we discuss the convergence of these clonogenic studies with contemporary radiosensitivity studies that use cell surface markers to identify cancer-initiating cells. Implications for and uncertainties regarding incorporation of these concepts into the practice of modern radiation oncology are discussed.

40 CFR Table 5 to Subpart Uuu of... - Initial Compliance With Metal HAP Emission Limits for Catalytic Cracking Units

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 12 2010-07-01 2010-07-01 true Initial Compliance With Metal HAP Emission Limits for Catalytic Cracking Units 5 Table 5 to Subpart UUU of Part 63 Protection of Environment..., Subpt. UUU, Table 5 Table 5 to Subpart UUU of Part 63—Initial Compliance With Metal HAP Emission Limits...

Initial embryology and pluripotent stem cells in the pig - the quest for establishing the pig as a model for cell therapy

DEFF Research Database (Denmark)

Secher, Jan; Callesen, Henrik; Freude, Karla Kristine

2016-01-01

genetically modified pigs emerged. Over the past years, renewed interest in porcine PSCs has sparked activities in deriving in particular porcine induced pluripotent stem cells to develop the pig as a faithful model for studying the potentials and risks associated with induced pluripotent stem cell......The quest for porcine pluripotent stem cells (PSCs) was initiated in the early 90s. Initially, it was the intention to benefit from these cells for production of genetically modified pigs using homologous recombination followed by derivation of chimeric offspring; a technology that has been used...... to produce genetically modified mice since the mid-80s. However, no convincing reports on the generation of bona fide porcine embryonic stem cells or embryonic germ cells resulted from these activities, and with the advent of somatic cell nuclear transfer during the late 90s, alternative methods for creating...

UE-Initiated Cell Reselection Game for Cell Load Balancing in a Wireless Network

Directory of Open Access Journals (Sweden)

Jaesung Park

2018-01-01

Full Text Available A user changes its serving cell if the quality of experience (QoE provided by the current serving cell is not satisfactory. Since users reselect cells to increase their QoEs selfishly, the system resource efficiency can be deteriorated and a system can be unstable if users are not driven to cooperate appropriately. In this paper, inspired by the minority game (MG model, we design a UE-initiated cell reselection policy. The MG has a salient characteristic that the number of players who win the game converges to a prespecified value even though players act selfishly without knowing the actions taken by the other players. Using the MG model, we devise a rule by which each UE plays a cell reselection game. We also design a criterion that a system controller uses to determine the result of a game and public information sent by a system controller to induce implicit cooperation among UEs. The simulation results show that compared with noncooperative method the proposed method increases not only the system performance, such as cell load balance index and system utility, but also the performance of UEs in terms of a downlink data rate and an outage probability received from a system.

Ovarian tumor-initiating cells display a flexible metabolism

International Nuclear Information System (INIS)

Anderson, Angela S.; Roberts, Paul C.; Frisard, Madlyn I.; Hulver, Matthew W.; Schmelz, Eva M.

2014-01-01

An altered metabolism during ovarian cancer progression allows for increased macromolecular synthesis and unrestrained growth. However, the metabolic phenotype of cancer stem or tumor-initiating cells, small tumor cell populations that are able to recapitulate the original tumor, has not been well characterized. In the present study, we compared the metabolic phenotype of the stem cell enriched cell variant, MOSE-L FFLv (TIC), derived from mouse ovarian surface epithelial (MOSE) cells, to their parental (MOSE-L) and benign precursor (MOSE-E) cells. TICs exhibit a decrease in glucose and fatty acid oxidation with a concomitant increase in lactate secretion. In contrast to MOSE-L cells, TICs can increase their rate of glycolysis to overcome the inhibition of ATP synthase by oligomycin and can increase their oxygen consumption rate to maintain proton motive force when uncoupled, similar to the benign MOSE-E cells. TICs have an increased survival rate under limiting conditions as well as an increased survival rate when treated with AICAR, but exhibit a higher sensitivity to metformin than MOSE-E and MOSE-L cells. Together, our data show that TICs have a distinct metabolic profile that may render them flexible to adapt to the specific conditions of their microenvironment. By better understanding their metabolic phenotype and external environmental conditions that support their survival, treatment interventions can be designed to extend current therapy regimens to eradicate TICs. - Highlights: • Ovarian cancer TICs exhibit a decreased glucose and fatty acid oxidation. • TICs are more glycolytic and have highly active mitochondria. • TICs are more resistant to AICAR but not metformin. • A flexible metabolism allows TICs to adapt to their microenvironment. • This flexibility requires development of specific drugs targeting TIC-specific changes to prevent recurrent TIC outgrowth

Ovarian tumor-initiating cells display a flexible metabolism

Energy Technology Data Exchange (ETDEWEB)

Anderson, Angela S. [Department of Human Nutrition, Foods, and Exercise, Virginia Tech, Blacksburg, VA (United States); Roberts, Paul C. [Biomedical Science and Pathobiology, Virginia Tech, Blacksburg, VA (United States); Frisard, Madlyn I. [Department of Human Nutrition, Foods, and Exercise, Virginia Tech, Blacksburg, VA (United States); Hulver, Matthew W., E-mail: hulvermw@vt.edu [Department of Human Nutrition, Foods, and Exercise, Virginia Tech, Blacksburg, VA (United States); Schmelz, Eva M., E-mail: eschmelz@vt.edu [Department of Human Nutrition, Foods, and Exercise, Virginia Tech, Blacksburg, VA (United States)

2014-10-15

An altered metabolism during ovarian cancer progression allows for increased macromolecular synthesis and unrestrained growth. However, the metabolic phenotype of cancer stem or tumor-initiating cells, small tumor cell populations that are able to recapitulate the original tumor, has not been well characterized. In the present study, we compared the metabolic phenotype of the stem cell enriched cell variant, MOSE-L{sub FFLv} (TIC), derived from mouse ovarian surface epithelial (MOSE) cells, to their parental (MOSE-L) and benign precursor (MOSE-E) cells. TICs exhibit a decrease in glucose and fatty acid oxidation with a concomitant increase in lactate secretion. In contrast to MOSE-L cells, TICs can increase their rate of glycolysis to overcome the inhibition of ATP synthase by oligomycin and can increase their oxygen consumption rate to maintain proton motive force when uncoupled, similar to the benign MOSE-E cells. TICs have an increased survival rate under limiting conditions as well as an increased survival rate when treated with AICAR, but exhibit a higher sensitivity to metformin than MOSE-E and MOSE-L cells. Together, our data show that TICs have a distinct metabolic profile that may render them flexible to adapt to the specific conditions of their microenvironment. By better understanding their metabolic phenotype and external environmental conditions that support their survival, treatment interventions can be designed to extend current therapy regimens to eradicate TICs. - Highlights: • Ovarian cancer TICs exhibit a decreased glucose and fatty acid oxidation. • TICs are more glycolytic and have highly active mitochondria. • TICs are more resistant to AICAR but not metformin. • A flexible metabolism allows TICs to adapt to their microenvironment. • This flexibility requires development of specific drugs targeting TIC-specific changes to prevent recurrent TIC outgrowth.

Brain tumor initiating cells adapt to restricted nutrition through preferential glucose uptake.

Science.gov (United States)

Flavahan, William A; Wu, Qiulian; Hitomi, Masahiro; Rahim, Nasiha; Kim, Youngmi; Sloan, Andrew E; Weil, Robert J; Nakano, Ichiro; Sarkaria, Jann N; Stringer, Brett W; Day, Bryan W; Li, Meizhang; Lathia, Justin D; Rich, Jeremy N; Hjelmeland, Anita B

2013-10-01

Like all cancers, brain tumors require a continuous source of energy and molecular resources for new cell production. In normal brain, glucose is an essential neuronal fuel, but the blood-brain barrier limits its delivery. We now report that nutrient restriction contributes to tumor progression by enriching for brain tumor initiating cells (BTICs) owing to preferential BTIC survival and to adaptation of non-BTICs through acquisition of BTIC features. BTICs outcompete for glucose uptake by co-opting the high affinity neuronal glucose transporter, type 3 (Glut3, SLC2A3). BTICs preferentially express Glut3, and targeting Glut3 inhibits BTIC growth and tumorigenic potential. Glut3, but not Glut1, correlates with poor survival in brain tumors and other cancers; thus, tumor initiating cells may extract nutrients with high affinity. As altered metabolism represents a cancer hallmark, metabolic reprogramming may maintain the tumor hierarchy and portend poor prognosis.

Hedgehog-GLI signaling drives self-renewal and tumorigenicity of human melanoma-initiating cells.

Science.gov (United States)

Santini, Roberta; Vinci, Maria C; Pandolfi, Silvia; Penachioni, Junia Y; Montagnani, Valentina; Olivito, Biagio; Gattai, Riccardo; Pimpinelli, Nicola; Gerlini, Gianni; Borgognoni, Lorenzo; Stecca, Barbara

2012-09-01

The question of whether cancer stem/tumor-initiating cells (CSC/TIC) exist in human melanomas has arisen in the last few years. Here, we have used nonadherent spheres and the aldehyde dehydrogenase (ALDH) enzymatic activity to enrich for CSC/TIC in a collection of human melanomas obtained from a broad spectrum of sites and stages. We find that melanomaspheres display extensive in vitro self-renewal ability and sustain tumor growth in vivo, generating human melanoma xenografts that recapitulate the phenotypic composition of the parental tumor. Melanomaspheres express high levels of Hedgehog (HH) pathway components and of embryonic pluripotent stem cell factors SOX2, NANOG, OCT4, and KLF4. We show that human melanomas contain a subset of cells expressing high ALDH activity (ALDH(high)), which is endowed with higher self-renewal and tumorigenic abilities than the ALDH(low) population. A good correlation between the number of ALDH(high) cells and sphere formation efficiency was observed. Notably, both pharmacological inhibition of HH signaling by the SMOOTHENED (SMO) antagonist cyclopamine and GLI antagonist GANT61 and stable expression of shRNA targeting either SMO or GLI1 result in a significant decrease in melanoma stem cell self-renewal in vitro and a reduction in the number of ALDH(high) melanoma stem cells. Finally, we show that interference with the HH-GLI pathway through lentiviral-mediated silencing of SMO and GLI1 drastically diminishes tumor initiation of ALDH(high) melanoma stem cells. In conclusion, our data indicate an essential role of the HH-GLI1 signaling in controlling self-renewal and tumor initiation of melanoma CSC/TIC. Targeting HH-GLI1 is thus predicted to reduce the melanoma stem cell compartment. Copyright © 2012 AlphaMed Press.

Modeling initiation of Ewing sarcoma in human neural crest cells.

Directory of Open Access Journals (Sweden)

Cornelia von Levetzow

2011-04-01

Full Text Available Ewing sarcoma family tumors (ESFT are aggressive bone and soft tissue tumors that express EWS-ETS fusion genes as driver mutations. Although the histogenesis of ESFT is controversial, mesenchymal (MSC and/or neural crest (NCSC stem cells have been implicated as cells of origin. For the current study we evaluated the consequences of EWS-FLI1 expression in human embryonic stem cell-derived NCSC (hNCSC. Ectopic expression of EWS-FLI1 in undifferentiated hNCSC and their neuro-mesenchymal stem cell (hNC-MSC progeny was readily tolerated and led to altered expression of both well established as well as novel EWS-FLI1 target genes. Importantly, whole genome expression profiling studies revealed that the molecular signature of established ESFT is more similar to hNCSC than any other normal tissue, including MSC, indicating that maintenance or reactivation of the NCSC program is a feature of ESFT pathogenesis. Consistent with this hypothesis, EWS-FLI1 induced hNCSC genes as well as the polycomb proteins BMI-1 and EZH2 in hNC-MSC. In addition, up-regulation of BMI-1 was associated with avoidance of cellular senescence and reversible silencing of p16. Together these studies confirm that, unlike terminally differentiated cells but consistent with bone marrow-derived MSC, NCSC tolerate expression of EWS-FLI1 and ectopic expression of the oncogene initiates transition to an ESFT-like state. In addition, to our knowledge this is the first demonstration that EWS-FLI1-mediated induction of BMI-1 and epigenetic silencing of p16 might be critical early initiating events in ESFT tumorigenesis.

The initiation of lateral roots in the primary roots of maize (Zea mays L.) implies a reactivation of cell proliferation in a group of founder pericycle cells.

Science.gov (United States)

Alarcón, M Victoria; Lloret, Pedro G; Martín-Partido, Gervasio; Salguero, Julio

2016-03-15

The initiation of lateral roots (LRs) has generally been viewed as a reactivation of proliferative activity in pericycle cells that are committed to initiate primordia. However, it is also possible that pericycle founder cells that initiate LRs never cease proliferative activity but rather are displaced to the most distal root zones while undertaking successive stages of LR initiation. In this study, we tested these two alternative hypotheses by examining the incorporation of 5-bromo-2'-deoxyuridine (BrdU) into the DNA of meristematic root cells of Zea mays. According to the values for the length of the cell cycle and values for cell displacement along the maize root, our results strongly suggest that pericycle cells that initiate LR primordia ceased proliferative activity upon exiting the meristematic zone. This finding is supported by the existence of a root zone between 4 and 20mm from the root cap junction, in which neither mitotic cells nor labelled nuclei were observed in phloem pericycle cells. Copyright © 2016 Elsevier GmbH. All rights reserved.

LGR5 and Nanog identify stem cell signature of pancreas beta cells which initiate pancreatic cancer.

Science.gov (United States)

Amsterdam, Abraham; Raanan, Calanit; Schreiber, Letizia; Polin, Nava; Givol, David

2013-04-05

Pancreas cancer, is the fourth leading cause of cancer death but its cell of origin is controversial. We compared the localization of stem cells in normal and cancerous pancreas using antibodies to the stem cell markers Nanog and LGR5. Here we show, for the first time, that LGR5 is expressed in normal pancreas, exclusively in the islets of Langerhans and it is co-localized, surprisingly, with Nanog and insulin in clusters of beta cells. In cancerous pancreas Nanog and LGR5 are expressed in the remaining islets and in all ductal cancer cells. We observed insulin staining among the ductal cancer cells, but not in metastases. This indicates that the islet's beta cells, expressing LGR5 and Nanog markers are the initiating cells of pancreas cancer, which migrated from the islets to form the ductal cancerous tissue, probably after mutation and de-differentiation. This discovery may facilitate treatment of this devastating cancer. Copyright © 2013 Elsevier Inc. All rights reserved.

Modulation of the androgenetic response in diverse skin cell types: the pilosebaceous unit

International Nuclear Information System (INIS)

Zurvarra, F.; Kerner, N.; Hagelin, K.

2009-01-01

Androgens play a central role in diverse morphogenetic processes of the skin. Hair growth and follicular cycle are regulated in part by androgens. Androgens also play a key function, together with other receptors such as the PPARs receptors family, on the proliferation and differentiation of the sebaceous gland that forms part of the pilosebaceous unit and influences hair growth and skin well-being. UV radiation may affect androgens regulation of skin homeostasis. Objectives: to study the modulation of androgenetic response related to UV radiation on the pilosebaceous unit, in two skin conditions: androgenetic alopecia and acne, both affecting skin and constituting major concerns for affected individuals. Methods: primary cultures of cells and established cell lines from the pilosebaceous unit: dermal papillae cells, keratinocytes and sebocytes. Analysis of lipid content, inflammatory response and proliferation of cells under the influence of androgens, PPARs ligands and UVR. Results: sebocytes primary cultures were obtained from human sebaceous glands. Proliferation and differentiation, as well as the expression of proinflammatory molecules (IL-1, TNF alpha, iNOs) and lipogenic enzymes (FASN) under androgens and UV treatment were assessed. The response to androgens under UV exposure was also analyzed in dermal papillae cells in culture. (authors)

CD73 Regulates Stemness and Epithelial-Mesenchymal Transition in Ovarian Cancer-Initiating Cells

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Michela Lupia

2018-04-01

Full Text Available Summary: Cancer-initiating cells (CICs have been implicated in tumor development and aggressiveness. In ovarian carcinoma (OC, CICs drive tumor formation, dissemination, and recurrence, as well as drug resistance, thus accounting for the high death-to-incidence ratio of this neoplasm. However, the molecular mechanisms that underlie such a pathogenic role of ovarian CICs (OCICs remain elusive. Here, we have capitalized on primary cells either from OC or from its tissues of origin to obtain the transcriptomic profile associated with OCICs. Among the genes differentially expressed in OCICs, we focused on CD73, which encodes the membrane-associated 5′-ectonucleotidase. The genetic inactivation of CD73 in OC cells revealed that this molecule is causally involved in sphere formation and tumor initiation, thus emerging as a driver of OCIC function. Furthermore, functional inhibition of CD73 via either a chemical compound or a neutralizing antibody reduced sphere formation and tumorigenesis, highlighting the druggability of CD73 in the context of OCIC-directed therapies. The biological function of CD73 in OCICs required its enzymatic activity and involved adenosine signaling. Mechanistically, CD73 promotes the expression of stemness and epithelial-mesenchymal transition-associated genes, implying a regulation of OCIC function at the transcriptional level. CD73, therefore, is involved in OCIC biology and may represent a therapeutic target for innovative treatments aimed at OC eradication. : Cavallaro et al. characterized the transcriptome of OCIC-enriched primary cultures and found CD73 as an upregulated gene. CD73 was then shown to regulate the expression of stemness and EMT-associated genes. The expression and function of CD73 in OCICs is required for tumor initiation, and CD73-targeted drugs decrease the rate of tumor take and inhibit cancer growth. Keywords: CD73, ovarian cancer, cancer-initiating cells, cancer stem cells, EMT, adenosine

Relationship between unit cell type and porosity and the fatigue behavior of selective laser melted meta-biomaterials.

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Amin Yavari, S; Ahmadi, S M; Wauthle, R; Pouran, B; Schrooten, J; Weinans, H; Zadpoor, A A

2015-03-01

Meta-materials are structures when their small-scale properties are considered, but behave as materials when their homogenized macroscopic properties are studied. There is an intimate relationship between the design of the small-scale structure and the homogenized properties of such materials. In this article, we studied that relationship for meta-biomaterials that are aimed for biomedical applications, otherwise known as meta-biomaterials. Selective laser melted porous titanium (Ti6Al4V ELI) structures were manufactured based on three different types of repeating unit cells, namely cube, diamond, and truncated cuboctahedron, and with different porosities. The morphological features, static mechanical properties, and fatigue behavior of the porous biomaterials were studied with a focus on their fatigue behavior. It was observed that, in addition to static mechanical properties, the fatigue properties of the porous biomaterials are highly dependent on the type of unit cell as well as on porosity. None of the porous structures based on the cube unit cell failed after 10(6) loading cycles even when the applied stress reached 80% of their yield strengths. For both other unit cells, higher porosities resulted in shorter fatigue lives for the same level of applied stress. When normalized with respect to their yield stresses, the S-N data points of structures with different porosities very well (R(2)>0.8) conformed to one single power law specific to the type of the unit cell. For the same level of normalized applied stress, the truncated cuboctahedron unit cell resulted in a longer fatigue life as compared to the diamond unit cell. In a similar comparison, the fatigue lives of the porous structures based on both truncated cuboctahedron and diamond unit cells were longer than that of the porous structures based on the rhombic dodecahedron unit cell (determined in a previous study). The data presented in this study could serve as a basis for design of porous biomaterials

Glycometabolic reprogramming associated with the initiation of human dental pulp stem cell differentiation.

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Wang, Linyan; Cheng, Li; Wang, Huning; Pan, Hongying; Yang, Hui; Shao, Meiying; Hu, Tao

2016-03-01

Glycometabolism, particularly mitochondrial oxidative phosphorylation (OXPHOS) and glycolysis, plays a central role in cell life activities. Glycometabolism can be reprogrammed to maintain the stemness or to induce the differentiation of stem cells, thereby regulating tissue repair and regeneration. However, research on the glycometabolism of human dental pulp stem cells (hDPSCs) remains scarce. Here, we investigated the relationship between glycometabolic reprogramming and initiation of hDPSC differentiation. We found the differentiation of hDPSCs commenced on day 3 when cells were cultured in mineralized medium. When cell differentiation commenced, mitochondria became elongated with well-developed cristae, and the oxygen consumption rate of mitochondria was enhanced, manifested as an increase in basal respiration, mitochondrial ATP production, and maximal respiration. Interestingly, glycolytic enzyme activities, glycolysis capacity, and glycolysis reserve were also upregulated at this time to match the powerful bioenergetic demands. More importantly, hDPSCs derived from different donors or cultured in various oxygen environments showed similar glycometabolic changes when they began to differentiate. Thus, glycometabolic reprogramming accompanies initiation of hDPSC differentiation and could potentially play a role in the regulation of dental pulp repair. © 2015 International Federation for Cell Biology.

A preliminary design and BOP cost analysis of M-C Power`s MCFC commerical unit

Energy Technology Data Exchange (ETDEWEB)

Chen, T.P. [Bechtel Corp, San Francisco, CA (United States)

1996-12-31

M-C Power Corporation plans to introduce its molten carbonate fuel cell (MCFC) market entry unit in the year 2000 for distributed and on-site power generation. Extensive efforts have been made to analyze the cell stack manufacturing costs. The major objective of this study is to conduct a detailed analysis of BOP costs based on an initial design of the market entry unit.

Dasatinib and Doxorubicin Treatment of Sarcoma Initiating Cells: A Possible New Treatment Strategy

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Ninna Aggerholm-Pedersen

2016-01-01

Full Text Available Background. One of the major challenges affecting sarcoma treatment outcome, particularly that of metastatic disease, is resistance to chemotherapy. Cancer-initiating cells are considered a major contributor to this resistance. Methods. An immortalised nontransformed human stromal (mesenchymal stem cell line hMSC-TERT4 and a transformed cell line hMSC-TERT20-CE8, known to form sarcoma-like tumours when implanted in immune-deficient mice, were used as models. Receptor tyrosine kinase (RTK activation was analysed by RTK arrays and cellular viability after tyrosine kinases inhibitor (TKI treatment with or without doxorubicin was assessed by MTS assay. Results. Initial results showed that the hMSC-TERT4 was more doxorubicin-sensitive while hMSC-TERT20-CE8 was less doxorubicin-sensitive evidenced by monitoring cell viability in the presence of doxorubicin at different doses. The epidermal growth factor receptor (EGFR was activated in both cell lines. However hMSC-TERT20-CE8 exhibited significantly higher expression of the EGFR ligands. EGFR inhibitors such as erlotinib and afatinib alone or in combination with doxorubicin failed to further decrease cell viability of hMSC-TERT20-CE8. However, inhibition with the TKI dasatinib in combination with doxorubicin decreased cell viability of the hMSC-TERT20-CE8 cell line. Conclusion. Our results demonstrate that dasatinib, but not EGFR-directed treatment, can decrease cell viability of stromal cancer stem cells less sensitive to doxorubicin.

Dasatinib and Doxorubicin Treatment of Sarcoma Initiating Cells: A Possible New Treatment Strategy.

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Aggerholm-Pedersen, Ninna; Demuth, Christina; Safwat, Akmal; Meldgaard, Peter; Kassem, Moustapha; Sandahl Sorensen, Boe

2016-01-01

Background. One of the major challenges affecting sarcoma treatment outcome, particularly that of metastatic disease, is resistance to chemotherapy. Cancer-initiating cells are considered a major contributor to this resistance. Methods. An immortalised nontransformed human stromal (mesenchymal) stem cell line hMSC-TERT4 and a transformed cell line hMSC-TERT20-CE8, known to form sarcoma-like tumours when implanted in immune-deficient mice, were used as models. Receptor tyrosine kinase (RTK) activation was analysed by RTK arrays and cellular viability after tyrosine kinases inhibitor (TKI) treatment with or without doxorubicin was assessed by MTS assay. Results. Initial results showed that the hMSC-TERT4 was more doxorubicin-sensitive while hMSC-TERT20-CE8 was less doxorubicin-sensitive evidenced by monitoring cell viability in the presence of doxorubicin at different doses. The epidermal growth factor receptor (EGFR) was activated in both cell lines. However hMSC-TERT20-CE8 exhibited significantly higher expression of the EGFR ligands. EGFR inhibitors such as erlotinib and afatinib alone or in combination with doxorubicin failed to further decrease cell viability of hMSC-TERT20-CE8. However, inhibition with the TKI dasatinib in combination with doxorubicin decreased cell viability of the hMSC-TERT20-CE8 cell line. Conclusion. Our results demonstrate that dasatinib, but not EGFR-directed treatment, can decrease cell viability of stromal cancer stem cells less sensitive to doxorubicin.

Dielectric Behavior of Low Microwave Loss Unit Cell for All Dielectric Metamaterial

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Tianhuan Luo

2015-01-01

Full Text Available With a deep study of the metamaterial, its unit cells have been widely extended from metals to dielectrics. The dielectric based unit cells attract much attention because of the advantage of easy preparation, tunability, and higher frequency response, and so forth. Using the conventional solid state method, we prepared a kind of incipient ferroelectrics (calcium titanate, CaTiO3 with higher microwave permittivity and lower loss, which can be successfully used to construct metamaterials. The temperature and frequency dependence of dielectric constant are also measured under different sintering temperatures. The dielectric spectra showed a slight permittivity decrease with the increase of temperature and exhibited a loss of 0.0005, combined with a higher microwave dielectric constant of ~167 and quality factor Q of 2049. Therefore, CaTiO3 is a kind of versatile and potential metamaterial unit cell. The permittivity of CaTiO3 at higher microwave frequency was also examined in the rectangular waveguide and we got the permittivity of 165, creating a new method to test permittivity at higher microwave frequency.

How dysregulated colonic crypt dynamics cause stem cell overpopulation and initiate colon cancer.

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Boman, Bruce M; Fields, Jeremy Z; Cavanaugh, Kenneth L; Guetter, Arthur; Runquist, Olaf A

2008-05-01

Based on investigation of the earliest colonic tissue alteration in familial adenomatous polyposis (FAP) patients, we present the hypothesis that initiation of colorectal cancer by adenomatous polyposis coli (APC) mutation is mediated by dysregulation of two cellular mechanisms. One involves differentiation, which normally decreases the proportion (proliferative fraction) of colonic crypt cells that can proliferate; the other is a cell cycle mechanism that simultaneously increases the probability that proliferative cells are in S phase. In normal crypts, stem cells (SC) at the crypt bottom generate rapidly proliferating cells, which undergo differentiation while migrating up the crypt. Our modeling of normal crypts suggests that these transitions are mediated by mechanisms that regulate proliferative fraction and S-phase probability. In FAP crypts, the population of rapidly proliferating cells is shifted upwards, as indicated by the labeling index (LI; i.e., crypt distribution of cells in S phase). Our analysis of FAP indicates that these transitions are delayed because the proliferative fraction and S-phase probability change more slowly as a function of crypt level. This leads to expansion of the proliferative cell population, including a subpopulation that has a low frequency of S-phase cells. We previously reported that crypt SC overpopulation explains the LI shift. Here, we determine that SCs (or cells having high stemness) are proliferative cells with a low probability of being in S phase. Thus, dysregulation of mechanisms that control proliferative fraction and S-phase probability explains how APC mutations induce SC overpopulation at the crypt bottom, shift the rapidly proliferating cell population upwards, and initiate colon tumorigenesis.

TRICE - A program for reconstructing 3D reciprocal space and determining unit-cell parameters

International Nuclear Information System (INIS)

Zou Xiaodong; Hovmoeller, Anders; Hovmoeller, Sven

2004-01-01

A program system-Trice-for reconstructing the 3D reciprocal lattice from an electron diffraction tilt series is described. The unit-cell parameters can be determined from electron diffraction patterns directly by Trice. The unit cell can be checked and the lattice type and crystal system can be determined from the 3D reciprocal lattice. Trice can be applied to all crystal systems and lattice types

Utilization of transmission probabilities in the calculation of unit-cell by the interface-current method

International Nuclear Information System (INIS)

Queiroz Bogado Leite, S. de.

1989-10-01

A widely used but otherwise physically incorrect assumption in unit-cell calculations by the method of interface currents in cylindrical or spherical geometries, is that of that of isotropic fluxes at the surfaces of the cell annular regions, when computing transmission probabilities. In this work, new interface-current relations are developed without making use of this assumption and the effects on calculated integral parameters are shown for an idealized unit-cell example. (author) [pt

Merkel Cell Polyomavirus Small T Antigen Initiates Merkel Cell Carcinoma-like Tumor Development in Mice.

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Verhaegen, Monique E; Mangelberger, Doris; Harms, Paul W; Eberl, Markus; Wilbert, Dawn M; Meireles, Julia; Bichakjian, Christopher K; Saunders, Thomas L; Wong, Sunny Y; Dlugosz, Andrzej A

2017-06-15

Merkel cell carcinoma (MCC) tumor cells express several markers detected in normal Merkel cells, a nonproliferative population of neuroendocrine cells that arise from epidermis. MCCs frequently contain Merkel cell polyomavirus (MCPyV) DNA and express viral transforming antigens, sT and tLT, but the role of these putative oncogenes in MCC development, and this tumor's cell of origin, are unknown. Using a panel of preterm transgenic mice, we show that epidermis-targeted coexpression of sT and the cell fate-determinant atonal bHLH transcription factor 1 (ATOH1) leads to development of widespread cellular aggregates, with histology and marker expression mimicking that of human intraepidermal MCC. The MCC-like tumor phenotype was dependent on the FBXW7-binding domain of sT, but not the sT-PP2A binding domain. Coexpression of MCPyV tLT did not appreciably alter the phenotype driven by either sT or sT combined with ATOH1. MCPyV sT, when coexpressed with ATOH1, is thus sufficient to initiate development of epidermis-derived MCC-like tumors in mice. Cancer Res; 77(12); 3151-7. ©2017 AACR . ©2017 American Association for Cancer Research.

Correlates of Human Papillomavirus (HPV) vaccination initiation and completion among 18-26 year olds in the United States.

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Adjei Boakye, Eric; Lew, Daphne; Muthukrishnan, Meera; Tobo, Betelihem B; Rohde, Rebecca L; Varvares, Mark A; Osazuwa-Peters, Nosayaba

2018-04-30

To examine correlates of HPV vaccination uptake in a nationally representative sample of 18-26-year-old adults. Young adults aged 18-26 years were identified from the 2014 and 2015 National Health Interview Survey (n = 7588). Survey-weighted multivariable logistic regression models estimated sociodemographic factors associated with HPV vaccine initiation (≥1 dose) and completion (≥3 doses). Approximately 27% of study participants had initiated the HPV vaccine and 16% had completed the HPV vaccine. Participants were less likely to initiate the vaccine if they were men [(adjusted odds ratio) 0.19; (95% confidence interval) 0.16-0.23], had a high school diploma (0.40; 0.31-0.52) or less (0.46; 0.32-0.64) vs. college graduates, and were born outside the United States (0.52; 0.40-0.69). But, participants were more likely to initiate the HPV if they visited the doctor's office 1-5 times (2.09; 1.56-2.81), or ≥ 6 times (1.86; 1.48-2.34) within the last 12 months vs. no visits. Odds of completing HPV vaccine uptake followed the same pattern as initiation. And after stratifying the study population by gender and foreign-born status, these variables remained statistically significant. In our nationally representative study, only one out of six 18-26 year olds completed the required vaccine doses. Men, individuals with high school or less education, and those born outside the United States were less likely to initiate and complete the HPV vaccination. Our findings suggest that it may be useful to develop targeted interventions to promote HPV vaccination among those in the catch-up age range.

Non-lethal heat treatment of cells results in reduction of tumor initiation and metastatic potential

International Nuclear Information System (INIS)

Kim, Yoo-Shin; Lee, Tae Hoon; O'Neill, Brian E.

2015-01-01

Non-lethal hyperthermia is used clinically as adjuvant treatment to radiation, with mixed results. Denaturation of protein during hyperthermia treatment is expected to synergize with radiation damage to cause cell cycle arrest and apoptosis. Alternatively, hyperthermia is known to cause tissue level changes in blood flow, increasing the oxygenation and radiosensitivity of often hypoxic tumors. In this study, we elucidate a third possibility, that hyperthermia alters cellular adhesion and mechanotransduction, with particular impact on the cancer stem cell population. We demonstrate that cell heating results in a robust but temporary loss of cancer cell aggressiveness and metastatic potential in mouse models. In vitro, this heating results in a temporary loss in cell mobility, adhesion, and proliferation. Our hypothesis is that the loss of cellular adhesion results in suppression of cancer stem cells and loss of tumor virulence and metastatic potential. Our study suggests that the metastatic potential of cancer is particularly reduced by the effects of heat on cellular adhesion and mechanotransduction. If true, this could help explain both the successes and failures of clinical hyperthermia, and suggest ways to target treatments to those who would most benefit. - Highlights: • Non-lethal hyperthermia treatment of cancer cells is shown to cause a reduction in rates of tumor initiation and metastasis. • Dynamic imaging of cells during heat treatment shows temporary changes in cell shape, cell migration, and cell proliferation. • Loss of adhesion may lead to the observed effect, which may disproportionately impact the tumor initiating cell fraction. • Loss or suppression of the tumor initiating cell fraction results in the observed loss of metastatic potential in vivo. • This result may lead to new approaches to synergizing hyperthermia with surgery, radiation, and chemotherapy

Non-lethal heat treatment of cells results in reduction of tumor initiation and metastatic potential

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Kim, Yoo-Shin; Lee, Tae Hoon; O' Neill, Brian E., E-mail: BEOneill@houstonmethodist.org

2015-08-14

Non-lethal hyperthermia is used clinically as adjuvant treatment to radiation, with mixed results. Denaturation of protein during hyperthermia treatment is expected to synergize with radiation damage to cause cell cycle arrest and apoptosis. Alternatively, hyperthermia is known to cause tissue level changes in blood flow, increasing the oxygenation and radiosensitivity of often hypoxic tumors. In this study, we elucidate a third possibility, that hyperthermia alters cellular adhesion and mechanotransduction, with particular impact on the cancer stem cell population. We demonstrate that cell heating results in a robust but temporary loss of cancer cell aggressiveness and metastatic potential in mouse models. In vitro, this heating results in a temporary loss in cell mobility, adhesion, and proliferation. Our hypothesis is that the loss of cellular adhesion results in suppression of cancer stem cells and loss of tumor virulence and metastatic potential. Our study suggests that the metastatic potential of cancer is particularly reduced by the effects of heat on cellular adhesion and mechanotransduction. If true, this could help explain both the successes and failures of clinical hyperthermia, and suggest ways to target treatments to those who would most benefit. - Highlights: • Non-lethal hyperthermia treatment of cancer cells is shown to cause a reduction in rates of tumor initiation and metastasis. • Dynamic imaging of cells during heat treatment shows temporary changes in cell shape, cell migration, and cell proliferation. • Loss of adhesion may lead to the observed effect, which may disproportionately impact the tumor initiating cell fraction. • Loss or suppression of the tumor initiating cell fraction results in the observed loss of metastatic potential in vivo. • This result may lead to new approaches to synergizing hyperthermia with surgery, radiation, and chemotherapy.

Residual tumor cells that drive disease relapse after chemotherapy do not have enhanced tumor initiating capacity.

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Ganapati V Hegde

Full Text Available Although chemotherapy is used to treat most advanced solid tumors, recurrent disease is still the major cause of cancer-related mortality. Cancer stem cells (CSCs have been the focus of intense research in recent years because they provide a possible explanation for disease relapse. However, the precise role of CSCs in recurrent disease remains poorly understood and surprisingly little attention has been focused on studying the cells responsible for re-initiating tumor growth within the original host after chemotherapy treatment. We utilized both xenograft and genetically engineered mouse models of non-small cell lung cancer (NSCLC to characterize the residual tumor cells that survive chemotherapy treatment and go on to cause tumor regrowth, which we refer to as tumor re-initiating cells (TRICs. We set out to determine whether TRICs display characteristics of CSCs, and whether assays used to define CSCs also provide an accurate readout of a cell's ability to cause tumor recurrence. We did not find consistent enrichment of CSC marker positive cells or enhanced tumor initiating potential in TRICs. However, TRICs from all models do appear to be in EMT, a state that has been linked to chemoresistance in numerous types of cancer. Thus, the standard CSC assays may not accurately reflect a cell's ability to drive disease recurrence.

Breast Cancer-Initiating Cells: Insights into Novel Treatment Strategies

International Nuclear Information System (INIS)

Santilli, Guido; Binda, Mara; Zaffaroni, Nadia; Daidone, Maria Grazia

2011-01-01

There is accumulating evidence that breast cancer may arise from mutated mammary stem/progenitor cells which have been termed breast cancer-initiating cells (BCIC). BCIC identified in clinical specimens based on membrane phenotype (CD44 + /CD24 −/low and/or CD133 + expression) or enzymatic activity of aldehyde dehydrogenase 1 (ALDH1 + ), have been demonstrated to have stem/progenitor cell properties, and are tumorigenic when injected in immunocompromized mice at very low concentrations. BCIC have also been isolated and in vitro propagated as non-adherent spheres of undifferentiated cells, and stem cell patterns have been recognized even in cancer cell lines. Recent findings indicate that aberrant regulation of self renewal is central to cancer stem cell biology. Alterations in genes involved in self-renewal pathways, such as Wnt, Notch, sonic hedgehog, PTEN and BMI, proved to play a role in breast cancer progression. Hence, targeting key elements mediating the self renewal of BCIC represents an attractive option, with a solid rationale, clearly identifiable molecular targets, and adequate knowledge of the involved pathways. Possible concerns are related to the poor knowledge of tolerance and efficacy of inhibiting self-renewal mechanisms, because the latter are key pathways for a variety of biological functions and it is unknown whether their interference would kill BCIC or simply temporarily stop them. Thus, efforts to develop BCIC-targeted therapies should not only be focused on interfering on self-renewal, but could seek to identify additional molecular targets, like those involved in regulating EMT-related pathways, in reversing the MDR phenotype, in inducing differentiation and controlling cell survival pathways

Computer programs for unit-cell determination in electron diffraction experiments

International Nuclear Information System (INIS)

Li, X.Z.

2005-01-01

A set of computer programs for unit-cell determination from an electron diffraction tilt series and pattern indexing has been developed on the basis of several well-established algorithms. In this approach, a reduced direct primitive cell is first determined from experimental data, in the means time, the measurement errors of the tilt angles are checked and minimized. The derived primitive cell is then checked for possible higher lattice symmetry and transformed into a proper conventional cell. Finally a least-squares refinement procedure is adopted to generate optimum lattice parameters on the basis of the lengths of basic reflections in each diffraction pattern and the indices of these reflections. Examples are given to show the usage of the programs

Healthy hospital food initiatives in the United States: time to ban sugar sweetened beverages to reduce childhood obesity.

Science.gov (United States)

Wojcicki, Janet M

2013-06-01

While childhood obesity is a global problem, the extent and severity of the problem in United States, has resulted in a number of new initiatives, including recent hospital initiatives to limit the sale of sweetened beverages and other high calorie drinks in hospital vending machines and cafeterias. These proposed policy changes are not unique to United States, but are more comprehensive in the number of proposed hospitals that they will impact. Meanwhile, however, it is advised, that these initiatives should focus on banning sugar sweetened beverages, including sodas, 100% fruit juice and sports drinks, from hospital cafeterias and vending machines instead of limiting their presence, so as to ensure the success of these programs in reducing the prevalence of childhood obesity. If US hospitals comprehensively remove sugar sweetened beverages from their cafeterias and vending machines, these programs could subsequently become a model for efforts to address childhood obesity in other areas of the world. Hospitals should be a model for health care reform in their communities and removing sugar sweetened beverages is a necessary first step. ©2013 Foundation Acta Paediatrica. Published by Blackwell Publishing Ltd.

Islet immunity and beta cell reserve of indigenous Black South Africans with ketoacidosis at initial diagnosis of diabetes.

Science.gov (United States)

Ekpebegh, Chukwuma; Longo-Mbenza, Benjamin; Blanco-Blanco, Ernesto

2013-01-01

Islet immunity and beta cell reserve status were utilized to classify persons with ketoacidosis as the initial manifestation of diabetes. The clinical features of the various diabetes classes were also characterized. Prospective cross sectional study. Nelson Mandela Academic Hospital, Mthatha, Eastern Cape Province, South Africa. Indigenous Black South Africans with ketoacidosis as the initial manifestation of diabetes. Islet immunity and beta cell reserve were respectively assessed using serum anti-glutamic acid decarboxylase 65 (GAD) antibody and serum C-peptide after 1 mg of intravenous glucagon. Serum anti-GAD 65 antibody > or = 5 units/L and or = 0.5 ng/mL and < 0.5 ng/mL, respectively. The proportions of patients with A+beta-, A+beta+, A-beta- and A-beta+ and their clinical characteristics were determined. Of the 38 males and 33 females who participated in the study, patients were categorized in various classes: A-beta+, 46.5% (n=33/ 71); A-beta-, 26.8% (n=19/71); A+beta-, 22.5% (n=16/71); and A+beta+, 4.2% (n=3/71). The ages of the various classes were: 41.8 +/- 13.8 years for A-beta+ (n=33); 36.5 +/- 14.6 years for A-beta- (n=19); and 20.6 +/- 7.1 years for the combination of A+beta- with A+beta+ (n=19) (P<.0001, P<.0001 for the combination of A+beta- and A+beta+ vs A-beta+, P=.001 for the combination of A+beta- and A+beta+ vs A-beta-and P=.2 for A-beta- vs A-beta+. The clinical features of type 2 diabetes were most prevalent in A-beta+ class while the A+beta- and A+beta+ groups had the clinical profile of type 1A diabetes. Most of the indigenous Black South African patients with ketoacidosis as the initial manifestation of diabetes had islet immunity, beta cell reserve status and clinical profiles of type 2 diabetes.

Ambulatory cell phone injuries in the United States: an emerging national concern.

Science.gov (United States)

Smith, Daniel C; Schreiber, Kristin M; Saltos, Andreas; Lichenstein, Sarah B; Lichenstein, Richard

2013-12-01

Over the past 15 years, the use of cell phones has increased 8-fold in the United States. Cell phone use has been shown to increase crash risks for drivers, but no systematic analyses have described injuries related to ambulatory cell phone use. The purpose of this study is to describe and quantitate injuries and deaths among persons using cell phones while walking. We searched the National Electronic Injury Surveillance System (NEISS) for emergency department (ED) reports of injuries related to phone use. The cases that returned were screened initially using words that would eliminate cases unlikely to be related to cell phone use and walking, possibly linked to distraction. The resulting cases were randomized and evaluated for consistency with predetermined case definitions by two authors blinded to the dates of the incidents. Cases that were disagreed upon were evaluated in a second screening by both authors for final case determination. National ED visit rates were estimated based on NEISS sampling methods. Annual variations were analyzed using linear regression with a restricted maximum likelihood approach. Our screening process identified 5,754 possible cases that occurred between 2000 and 2011, and 310 were agreed on as cases of cell-phone-induced distraction. The majority of the patients were female (68%) and 40 years of age or younger (54%). The primary mechanism of injury was a fall (72%), and most patients were treated and released from the ED (85%). No patients died from their injuries while they were in the ED. Linear modeling by year revealed a statistically significant increase in distraction injury rates over the years of study (pcell phone use has been increasing. More research is needed to determine the risks associated with walking and talking on a cell phone and to develop strategies for intervention. Cell phone use continues to increase both at home and outdoor environments. The use of smart phones, with their more enticing features, increases

Sonic Hedgehog Initiates Cochlear Hair Cell Regeneration through Downregulation of Retinoblastoma Protein

Science.gov (United States)

Lu, Na; Chen, Yan; Wang, Zhengmin; Chen, Guoling; Lin, Qin; Chen, Zheng-Yi; Li, Huawei

2013-01-01

Cell cycle re-entry by cochlear supporting cells and/or hair cells is considered one of the best approaches for restoring hearing loss as a result of hair cell damage. To identify mechanisms that can be modulated to initiate cell cycle re-entry and hair cell regeneration, we studied the effect of activating the sonic hedgehog (Shh) pathway. We show that Shh signaling in postnatal rat cochleae damaged by neomycin leads to renewed proliferation of supporting cells and hair cells. Further, proliferating supporting cells are likely to transdifferentiate into hair cells. Shh treatment leads to inhibition of retinoblastoma protein (pRb) by increasing phosphorylated pRb and reducing retinoblastoma gene transcription. This results in upregulation of cyclins B1, D2, and D3, and CDK1. These results suggest that Shh signaling induces cell cycle re-entry in cochlear sensory epithelium and the production of new hair cells, in part by attenuating pRb function. This study provides an additional route to modulate pRb function with important implications in mammalian hair cell regeneration. PMID:23211596

The Initial Test Programme Features for the Advanced Korean NPPs (Shin–Kori NPP Units 3&4)

International Nuclear Information System (INIS)

Sul, Y.S.

2015-01-01

Korea has developed the Advanced Power Reactor 1400 (APR1400), an evolutionary pressurised water reactor and has obtained the standard design approval in 2002. As of 2014, eight nuclear power plants (NPPs) are in preparation for operation or under construction, four in Korea (SKN 3&4, SUN 1&2) and four in UAE (BNPP 1, 2, 3&4), and four NPPs are in planning in Korea (SKN 5&6, SUN 3&4). Especially, SKN Units 3&4 are the first construction NPPs for the APR1400 and are currently in the final stage to get Operating Licence (OL). The initial test programme for NPPs begins as systems and components are turned over to the startup organization and ends with completion of the Power Ascension Tests (PATs). For SKN Unit 3, the Pre-core Hot Functional Testing has been successfully completed and the initial fuel loading would proceed after getting OL. The SKN Unit 4 is preparing for the CHT (Cold Hydrostatic Test). The SKN 3&4 has many new and advanced design features and so has developed the test programmes to demonstrate that those advanced design features can be safely operated and the performance levels can be maintained in accordance with approved safety requirements. Among those test programs, the examples of test programs, newly introduced ones compared to the previous NPPs are as follows; – SIT (Safety Injection Tank) Blowdown Test with FD (Fluidic Device) – IRWST (In-Containment Refueling Water Storage Tank) In-Plant Test – POSRV (Pilot Operated Safety Relief Valve) Test – Low Power Physics Testing and PAT considering FOAK (First Of A Kind) unit – Safe Shutdown Test with DCS (Distrubuted Control System) Fail and CMF (Common Mode Failure) for Safety Instrumentation and Control System. (author)

Role of stem cells in tumor initiation, metastasis formation and their use in cancer therapy

International Nuclear Information System (INIS)

Altaner, C.; Altanerova, V.

2010-01-01

This review considers recent advances in the stem cell field focusing on the challenges and opportunities for their use in clinical practice. Various kinds of stem cells and their roles in the human organism are in the review described. Attention is given to the role of mesenchymal stem cells as a potential tool in regenerative medicine. The origin and consequences of existence of tumor-initiating cells known as cancer stem cells is discussed also in context of metastasis formation. It seems that tumor-initiating cells might be responsible for resistance to many conventional cancer therapies, which might explain the limitations of these therapeutic modalities. Furthermore, the review focuses to tumor homing property of adult mesenchymal (stromal) stem cells. The feasibility of mesenchymal stem cells isolation from human adipose tissue, their genetic modifications with suicide genes together with ability to find tumor in the organism make them an attractive vehicle for cancer therapy without systemic toxicity. Published achievements from our laboratory in stem cell-based gene cancer therapy are shortly summarized. Generally, it is believed that the stem cell therapies might be ideal future treatment modality for inherited, degenerative diseases and in curing human malignancies as well. (author)

LGR4 modulates breast cancer initiation, metastasis, and cancer stem cells.

Science.gov (United States)

Yue, Zhiying; Yuan, Zengjin; Zeng, Li; Wang, Ying; Lai, Li; Li, Jing; Sun, Peng; Xue, Xiwen; Qi, Junyi; Yang, Zhengfeng; Zheng, Yansen; Fang, Yuanzhang; Li, Dali; Siwko, Stefan; Li, Yi; Luo, Jian; Liu, Mingyao

2018-05-01

The fourth member of the leucine-rich repeat-containing GPCR family (LGR4, frequently referred to as GPR48) and its cognate ligands, R-spondins (RSPOs) play crucial roles in the development of multiple organs as well as the survival of adult stem cells by activation of canonical Wnt signaling. Wnt/β-catenin signaling acts to regulate breast cancer; however, the molecular mechanisms determining its spatiotemporal regulation are largely unknown. In this study, we identified LGR4 as a master controller of Wnt/β-catenin signaling-mediated breast cancer tumorigenesis, metastasis, and cancer stem cell (CSC) maintenance. LGR4 expression in breast tumors correlated with poor prognosis. Either Lgr4 haploinsufficiency or mammary-specific deletion inhibited mouse mammary tumor virus (MMTV)- PyMT- and MMTV- Wnt1-driven mammary tumorigenesis and metastasis. Moreover, LGR4 down-regulation decreased in vitro migration and in vivo xenograft tumor growth and lung metastasis. Furthermore, Lgr4 deletion in MMTV- Wnt1 tumor cells or knockdown in human breast cancer cells decreased the number of functional CSCs by ∼90%. Canonical Wnt signaling was impaired in LGR4-deficient breast cancer cells, and LGR4 knockdown resulted in increased E-cadherin and decreased expression of N-cadherin and snail transcription factor -2 ( SNAI2) (also called SLUG), implicating LGR4 in regulation of epithelial-mesenchymal transition. Our findings support a crucial role of the Wnt signaling component LGR4 in breast cancer initiation, metastasis, and breast CSCs.-Yue, Z., Yuan, Z., Zeng, L., Wang, Y., Lai, L., Li, J., Sun, P., Xue, X., Qi, J., Yang, Z., Zheng, Y., Fang, Y., Li, D., Siwko, S., Li, Y., Luo, J., Liu, M. LGR4 modulates breast cancer initiation, metastasis, and cancer stem cells.

Application of Artificial Thunderstorm Cells for the Investigation of Lightning Initiation Problems between a Thundercloud and the Ground

Science.gov (United States)

Temnikov, A. G.; Chernensky, L. L.; Orlov, A. V.; Lysov, N. Y.; Zhuravkova, D. S.; Belova, O. S.; Gerastenok, T. K.

2017-12-01

The results of the experimental application of artificial thunderstorm cells of negative and positive polarities for the investigation of the lightning initiation problems between the thundercloud and the ground using model hydrometeor arrays are presented. Possible options of the initiation and development of a discharge between the charged cloud and the ground in the presence of model hydrometeors are established. It is experimentally shown that groups of large hydrometeors of various shapes significantly increase the probability of channel discharge initiation between the artificial thunderstorm cell and the ground, especially in the case of positive polarity of the cloud. The authors assume that large hail arrays in the thundercloud can initiate the preliminary breakdown stage in the lower part of the thundercloud or initiate and stimulate the propagation of positive lightning from its upper part. A significant effect of the shape of model hydrometeors and the way they are grouped on the processes of initiation and stimulation of the channel discharge propagation in the artificial thunderstorm cell of negative or positive polarity-ground gap is experimentally established. It is found that, in the case of negative polarity of a charged cloud, the group of conductive cylindrical hydrometeors connected by a dielectric string more effectively initiates the channel discharge between the artificial thunderstorm cell and the ground. In the case of positive polarity of the artificial thunderstorm cell, the best effect of the channel discharge initiation is achieved for model hydrometeors grouped together by the dielectric tape. The obtained results can be used in the development of the method for the directed artificial lightning initiation between the thundercloud and the ground.

40 CFR Appendix A to Part 76 - Phase I Affected Coal-Fired Utility Units With Group 1 or Cell Burner Boilers

Science.gov (United States)

2010-07-01

... Units With Group 1 or Cell Burner Boilers A Appendix A to Part 76 Protection of Environment... 1 or Cell Burner Boilers Table 1—Phase I Tangentially Fired Units State Plant Unit Operator ALABAMA... Vertically fired boiler. 2 Arch-fired boiler. Table 3—Phase I Cell Burner Technology Units State Plant Unit...

The T-ALL related gene BCL11B regulates the initial stages of human T-cell differentiation.

Science.gov (United States)

Ha, V L; Luong, A; Li, F; Casero, D; Malvar, J; Kim, Y M; Bhatia, R; Crooks, G M; Parekh, C

2017-11-01

The initial stages of T-cell differentiation are characterized by a progressive commitment to the T-cell lineage, a process that involves the loss of alternative (myelo-erythroid, NK, B) lineage potentials. Aberrant differentiation during these stages can result in T-cell acute lymphoblastic leukemia (T-ALL). However, the mechanisms regulating the initial stages of human T-cell differentiation are obscure. Through loss of function studies, we showed BCL11B, a transcription factor recurrently mutated T-ALL, is essential for T-lineage commitment, particularly the repression of NK and myeloid potentials, and the induction of T-lineage genes, during the initial stages of human T-cell differentiation. In gain of function studies, BCL11B inhibited growth of and induced a T-lineage transcriptional program in T-ALL cells. We found previously unknown differentiation stage-specific DNA binding of BCL11B at multiple T-lineage genes; target genes showed BCL11B-dependent expression, suggesting a transcriptional activator role for BCL11B at these genes. Transcriptional analyses revealed differences in the regulatory actions of BCL11B between human and murine thymopoiesis. Our studies show BCL11B is a key regulator of the initial stages of human T-cell differentiation and delineate the BCL11B transcriptional program, enabling the dissection of the underpinnings of normal T-cell differentiation and providing a resource for understanding dysregulations in T-ALL.

Effect of different photo-initiators and light curing units on degree of conversion of composites.

Science.gov (United States)

Brandt, William Cunha; Schneider, Luis Felipe Jochims; Frollini, Elisabete; Correr-Sobrinho, Lourenço; Sinhoreti, Mário Alexandre Coelho

2010-01-01

The aim of this study was to evaluate: (i) the absorption of photo-initiators and emission spectra of light curing units (LCUs); and (ii) the degree of conversion (DC) of experimental composites formulated with different photo-initiators when activated by different LCUs. Blends of BisGMA, UDMA, BisEMA and TEGDMA with camphorquinone (CQ) and/ or 1-phenyl-1,2-propanedione (PPD) were prepared. Dimethylaminoethyl methacrylate (DMAEMA) was used as co-initiator. Each mixture was loaded with 65 wt% of silanated filler particles. One quartz-tungsten-halogen - QTH (XL 2500, 3M/ESPE) and two lightemitting diode (LED) LCUs (UltraBlue IS, DMC and UltraLume LED 5, Ultradent) were used for activation procedures. Irradiance (mW/cm²) was calculated by the ratio of the output power by the area of the tip, and spectral distribution with a spectrometer (USB 2000). The absorption curve of each photo-initiator was determined using a spectrophotometer (Varian Cary 5G). DC was assessed by Fourier transformed infrared spectroscopy. Data were submitted to two-way ANOVA and Tukey's test (5%). No significant difference was found for DC values when using LED LCUs regardless of the photo-initiator type. However, PPD showed significantly lower DC values than composites with CQ when irradiated with QTH. PPD produced DC values similar to those of CQ, but it was dependent on the LCU type.

A heated vapor cell unit for DAVLL in atomic rubidium

OpenAIRE

McCarron, Daniel J.; Hughes, Ifan G.; Tierney, Patrick; Cornish, Simon L.

2007-01-01

The design and performance of a compact heated vapor cell unit for realizing a dichroic atomic vapor laser lock (DAVLL) for the D2 transitions in atomic rubidium is described. A 5 cm-long vapor cell is placed in a double-solenoid arrangement to produce the required magnetic field; the heat from the solenoid is used to increase the vapor pressure and correspondingly the DAVLL signal. We have characterized experimentally the dependence of important features of the DAVLL signal on magnetic field...

Mitochondrially targeted vitamin E succinate efficiently kills breast tumour-initiating cells in a complex II-dependent manner

International Nuclear Information System (INIS)

Yan, Bing; Stantic, Marina; Zobalova, Renata; Bezawork-Geleta, Ayenachew; Stapelberg, Michael; Stursa, Jan; Prokopova, Katerina; Dong, Lanfeng; Neuzil, Jiri

2015-01-01

Accumulating evidence suggests that breast cancer involves tumour-initiating cells (TICs), which play a role in initiation, metastasis, therapeutic resistance and relapse of the disease. Emerging drugs that target TICs are becoming a focus of contemporary research. Mitocans, a group of compounds that induce apoptosis of cancer cells by destabilising their mitochondria, are showing their potential in killing TICs. In this project, we investigated mitochondrially targeted vitamin E succinate (MitoVES), a recently developed mitocan, for its in vitro and in vivo efficacy against TICs. The mammosphere model of breast TICs was established by culturing murine NeuTL and human MCF7 cells as spheres. This model was verified by stem cell marker expression, tumour initiation capacity and chemotherapeutic resistance. Cell susceptibility to MitoVES was assessed and the cell death pathway investigated. In vivo efficacy was studied by grafting NeuTL TICs to form syngeneic tumours. Mammospheres derived from NeuTL and MCF7 breast cancer cells were enriched in the level of stemness, and the sphere cells featured altered mitochondrial function. Sphere cultures were resistant to several established anti-cancer agents while they were susceptible to MitoVES. Killing of mammospheres was suppressed when the mitochondrial complex II, the molecular target of MitoVES, was knocked down. Importantly, MitoVES inhibited progression of syngeneic HER2 high tumours derived from breast TICs by inducing apoptosis in tumour cells. These results demonstrate that using mammospheres, a plausible model for studying TICs, drugs that target mitochondria efficiently kill breast tumour-initiating cells. The online version of this article (doi:10.1186/s12885-015-1394-7) contains supplementary material, which is available to authorized users

Cancer-initiating cells derived from established cervical cell lines exhibit stem-cell markers and increased radioresistance

International Nuclear Information System (INIS)

López, Jacqueline; Poitevin, Adela; Mendoza-Martínez, Veverly; Pérez-Plasencia, Carlos; García-Carrancá, Alejandro

2012-01-01

Cancer-initiating cells (CICs) are proposed to be responsible for the generation of metastasis and resistance to therapy. Accumulating evidences indicates CICs are found among different human cancers and cell lines derived from them. Few studies address the characteristics of CICs in cervical cancer. We identify biological features of CICs from four of the best-know human cell lines from uterine cervix tumors. (HeLa, SiHa, Ca Ski, C-4 I). Cells were cultured as spheres under stem-cell conditions. Flow cytometry was used to detect expression of CD34, CD49f and CD133 antigens and Hoechst 33342 staining to identify side population (SP). Magnetic and fluorescence-activated cell sorting was applied to enrich and purify populations used to evaluate tumorigenicity in nude mice. cDNA microarray analysis and in vitro radioresistance assay were carried out under standard conditions. CICs, enriched as spheroids, were capable to generate reproducible tumor phenotypes in nu-nu mice and serial propagation. Injection of 1 × 10 3 dissociated spheroid cells induced tumors in the majority of animals, whereas injection of 1 × 10 5 monolayer cells remained nontumorigenic. Sphere-derived CICs expressed CD49f surface marker. Gene profiling analysis of HeLa and SiHa spheroid cells showed up-regulation of CICs markers characteristic of the female reproductive system. Importantly, epithelial to mesenchymal (EMT) transition-associated markers were found highly expressed in spheroid cells. More importantly, gene expression analysis indicated that genes required for radioresistance were also up-regulated, including components of the double-strand break (DSB) DNA repair machinery and the metabolism of reactive oxygen species (ROS). Dose-dependent radiation assay indicated indeed that CICs-enriched populations exhibit an increased resistance to ionizing radiation (IR). We characterized a self-renewing subpopulation of CICs found among four well known human cancer-derived cell lines (HeLa, Si

Automated assembling of single fuel cell units for use in a fuel cell stack

Science.gov (United States)

Jalba, C. K.; Muminovic, A.; Barz, C.; Nasui, V.

2017-05-01

The manufacturing of PEMFC stacks (POLYMER ELEKTROLYT MEMBRAN Fuel Cell) is nowadays still done by hand. Over hundreds of identical single components have to be placed accurate together for the construction of a fuel cell stack. Beside logistic problems, higher total costs and disadvantages in weight the high number of components produce a higher statistic interference because of faulty erection or material defects and summation of manufacturing tolerances. The saving of costs is about 20 - 25 %. Furthermore, the total weight of the fuel cells will be reduced because of a new sealing technology. Overall a one minute cycle time has to be aimed per cell at the manufacturing of these single components. The change of the existing sealing concept to a bonded sealing is one of the important requisites to get an automated manufacturing of single cell units. One of the important steps for an automated gluing process is the checking of the glue application by using of an image processing system. After bonding the single fuel cell the sealing and electrical function can be checked, so that only functional and high qualitative cells can get into further manufacturing processes.

Improved reproducibility of unit-cell parameters in macromolecular cryocrystallography by limiting dehydration during crystal mounting.

Science.gov (United States)

Farley, Christopher; Burks, Geoffry; Siegert, Thomas; Juers, Douglas H

2014-08-01

In macromolecular cryocrystallography unit-cell parameters can have low reproducibility, limiting the effectiveness of combining data sets from multiple crystals and inhibiting the development of defined repeatable cooling protocols. Here, potential sources of unit-cell variation are investigated and crystal dehydration during loop-mounting is found to be an important factor. The amount of water lost by the unit cell depends on the crystal size, the loop size, the ambient relative humidity and the transfer distance to the cooling medium. To limit water loss during crystal mounting, a threefold strategy has been implemented. Firstly, crystal manipulations are performed in a humid environment similar to the humidity of the crystal-growth or soaking solution. Secondly, the looped crystal is transferred to a vial containing a small amount of the crystal soaking solution. Upon loop transfer, the vial is sealed, which allows transport of the crystal at its equilibrated humidity. Thirdly, the crystal loop is directly mounted from the vial into the cold gas stream. This strategy minimizes the exposure of the crystal to relatively low humidity ambient air, improves the reproducibility of low-temperature unit-cell parameters and offers some new approaches to crystal handling and cryoprotection.

Mechanical properties of regular porous biomaterials made from truncated cube repeating unit cells: Analytical solutions and computational models.

Science.gov (United States)

Hedayati, R; Sadighi, M; Mohammadi-Aghdam, M; Zadpoor, A A

2016-03-01

Additive manufacturing (AM) has enabled fabrication of open-cell porous biomaterials based on repeating unit cells. The micro-architecture of the porous biomaterials and, thus, their physical properties could then be precisely controlled. Due to their many favorable properties, porous biomaterials manufactured using AM are considered as promising candidates for bone substitution as well as for several other applications in orthopedic surgery. The mechanical properties of such porous structures including static and fatigue properties are shown to be strongly dependent on the type of the repeating unit cell based on which the porous biomaterial is built. In this paper, we study the mechanical properties of porous biomaterials made from a relatively new unit cell, namely truncated cube. We present analytical solutions that relate the dimensions of the repeating unit cell to the elastic modulus, Poisson's ratio, yield stress, and buckling load of those porous structures. We also performed finite element modeling to predict the mechanical properties of the porous structures. The analytical solution and computational results were found to be in agreement with each other. The mechanical properties estimated using both the analytical and computational techniques were somewhat higher than the experimental data reported in one of our recent studies on selective laser melted Ti-6Al-4V porous biomaterials. In addition to porosity, the elastic modulus and Poisson's ratio of the porous structures were found to be strongly dependent on the ratio of the length of the inclined struts to that of the uninclined (i.e. vertical or horizontal) struts, α, in the truncated cube unit cell. The geometry of the truncated cube unit cell approaches the octahedral and cube unit cells when α respectively approaches zero and infinity. Consistent with those geometrical observations, the analytical solutions presented in this study approached those of the octahedral and cube unit cells when �

Multiple modes of action potential initiation and propagation in mitral cell primary dendrite

DEFF Research Database (Denmark)

Chen, Wei R; Shen, Gongyu Y; Shepherd, Gordon M

2002-01-01

recordings with computational modeling to analyze action-potential initiation and propagation in the primary dendrite. In response to depolarizing current injection or distal olfactory nerve input, fast Na(+) action potentials were recorded along the entire length of the primary dendritic trunk. With weak......-to-moderate olfactory nerve input, an action potential was initiated near the soma and then back-propagated into the primary dendrite. As olfactory nerve input increased, the initiation site suddenly shifted to the distal primary dendrite. Multi-compartmental modeling indicated that this abrupt shift of the spike......-initiation site reflected an independent thresholding mechanism in the distal dendrite. When strong olfactory nerve excitation was paired with strong inhibition to the mitral cell basal secondary dendrites, a small fast prepotential was recorded at the soma, which indicated that an action potential was initiated...

Electrochemical characterization of a polybenzimidazole-based high temperature proton exchange membrane unit cell

DEFF Research Database (Denmark)

Jespersen, Jesper Lebæk; Schaltz, Erik; Kær, Søren Knudsen

2009-01-01

This work constitutes detailed EIS (Electrochemical Impedance Spectroscopy) measurements on a PBIbased HT-PEM unit cell. By means of EIS the fuel cell is characterized in several modes of operation by varying the current density, temperature and the stoichiometry of the reactant gases. Using...

Initiation and continuation of long-acting reversible contraception in the United States military healthcare system.

Science.gov (United States)

Chiles, Daniel P; Roberts, Timothy A; Klein, David A

2016-09-01

Long-acting reversible contraception is more effective for pregnancy prevention than shorter-acting contraceptive methods and has the potential to reduce healthcare disparities and costs. However, long-acting reversible contraception is underused in the United States. One population of interest is beneficiaries of the United States military healthcare system who have access to universal healthcare, including no-cost, no-copay contraception with unlimited method switching, and comprise a large, actual use cohort. Efforts to increase long-acting reversible contraception initiation and continuation in this population may improve health outcomes and mitigate the profound consequences of unintended or mistimed pregnancy on readiness and cost to the military. We aimed to determine long-acting reversible contraception initiation and continuation rates among the diverse population with universal healthcare who are enrolled in the US military healthcare system. This study is a retrospective cohort of >1.7 million women, aged 14-40 years, who were enrolled in the US military healthcare system, TRICARE Prime, between October 2009 and September 2014. Individuals were assessed for long-acting reversible contraception initiation and continuation with the use of medical billing records. Method continuation and factors that were associated with early method discontinuation were evaluated with the Kaplan-Meier estimator and Cox proportional hazard models. During the study dates, 188,533 women initiated long-acting reversible contraception. Of these, 74.6% women selected intrauterine contraceptives. Method initiation rates remained relatively stable (41.7-50.1/1000 women/year) for intrauterine methods, although the rate for subdermal implants increased from 6.1-23.0/1000 women/year. In analysis of women who selected intrauterine contraceptives, 61.2% continued their method at 36 months, and 48.8% continued at 60 months. Among women who selected the implant, 32.0% continued their

Human NK cells selective targeting of colon cancer-initiating cells: A role for natural cytotoxicity receptors and MHC class i molecules

KAUST Repository

Tallerico, Rossana

2013-01-23

Tumor cell populations have been recently proposed to be composed of two compartments: tumor-initiating cells characterized by a slow and asymmetrical growth, and the "differentiated" cancer cells with a fast and symmetrical growth. Cancer stem cells or cancer-initiating cells (CICs) play a crucial role in tumor recurrence. The resistance of CICs to drugs and irradiation often allows them to survive traditional therapy. NK cells are potent cytotoxic lymphocytes that can recognize tumor cells. In this study, we have analyzed the NK cell recognition of tumor target cells derived from the two cancer cell compartments of colon adenocarcinoma lesions. Our data demonstrate that freshly purified allogeneic NK cells can recognize and kill colorectal carcinoma- derived CICs whereas the non-CIC counterpart of the tumors (differentiated tumor cells), either autologous or allogeneic, is less susceptible to NK cells. This difference in the NK cell susceptibility correlates with higher expression on CICs of ligands for NKp30 and NKp44 in the natural cytotoxicity receptor (NCR) group of activating NK receptors. In contrast, CICs express lower levels of MHC class I, known to inhibit NK recognition, on their surface than do the "differentiated" tumor cells. These data have been validated by confocal microscopy where NCR ligands and MHC class I molecule membrane distribution have been analyzed. Moreover, NK cell receptor blockade in cytotoxicity assays demonstrates that NCRs play a major role in the recognition of CIC targets. This study strengthens the idea that biology-based therapy harnessing NK cells could be an attractive opportunity in solid tumors. Copyright © 2013 by The American Association of Immunologists, Inc. All rights reserved.

Human NK cells selective targeting of colon cancer-initiating cells: A role for natural cytotoxicity receptors and MHC class i molecules

KAUST Repository

Tallerico, Rossana; Todaro, Matilde; Di Franco, Simone; MacCalli, Cristina; Garofalo, Cinzia; Sottile, Rosa; Palmieri, Camillo; Tirinato, Luca; Pangigadde, Pradeepa N.; La Rocca, Rosanna; Mandelboim, Ofer; Stassi, Giorgio; Di Fabrizio, Enzo M.; Parmiani, Giorgio; Moretta, Alessandro; Dieli, Francesco; Kã rre, Klas; Carbone, Ennio

2013-01-01

Tumor cell populations have been recently proposed to be composed of two compartments: tumor-initiating cells characterized by a slow and asymmetrical growth, and the "differentiated" cancer cells with a fast and symmetrical growth. Cancer stem cells or cancer-initiating cells (CICs) play a crucial role in tumor recurrence. The resistance of CICs to drugs and irradiation often allows them to survive traditional therapy. NK cells are potent cytotoxic lymphocytes that can recognize tumor cells. In this study, we have analyzed the NK cell recognition of tumor target cells derived from the two cancer cell compartments of colon adenocarcinoma lesions. Our data demonstrate that freshly purified allogeneic NK cells can recognize and kill colorectal carcinoma- derived CICs whereas the non-CIC counterpart of the tumors (differentiated tumor cells), either autologous or allogeneic, is less susceptible to NK cells. This difference in the NK cell susceptibility correlates with higher expression on CICs of ligands for NKp30 and NKp44 in the natural cytotoxicity receptor (NCR) group of activating NK receptors. In contrast, CICs express lower levels of MHC class I, known to inhibit NK recognition, on their surface than do the "differentiated" tumor cells. These data have been validated by confocal microscopy where NCR ligands and MHC class I molecule membrane distribution have been analyzed. Moreover, NK cell receptor blockade in cytotoxicity assays demonstrates that NCRs play a major role in the recognition of CIC targets. This study strengthens the idea that biology-based therapy harnessing NK cells could be an attractive opportunity in solid tumors. Copyright © 2013 by The American Association of Immunologists, Inc. All rights reserved.

The role of CD133 in normal human prostate stem cells and malignant cancer-initiating cells.

Science.gov (United States)

Vander Griend, Donald J; Karthaus, Wouter L; Dalrymple, Susan; Meeker, Alan; DeMarzo, Angelo M; Isaacs, John T

2008-12-01

Resolving the specific cell of origin for prostate cancer is critical to define rational targets for therapeutic intervention and requires the isolation and characterization of both normal human prostate stem cells and prostate cancer-initiating cells (CIC). Single epithelial cells from fresh normal human prostate tissue and prostate epithelial cell (PrEC) cultures derived from them were evaluated for the presence of subpopulations expressing stem cell markers and exhibiting stem-like growth characteristics. When epithelial cell suspensions containing cells expressing the stem cell marker CD133+ are inoculated in vivo, regeneration of stratified human prostate glands requires inductive prostate stromal cells. PrEC cultures contain a small subpopulation of CD133+ cells, and fluorescence-activated cell sorting-purified CD133+ PrECs self-renew and regenerate cell populations expressing markers of transit-amplifying cells (DeltaNp63), intermediate cells (prostate stem cell antigen), and neuroendocrine cells (CD56). Using a series of CD133 monoclonal antibodies, attachment and growth of CD133+ PrECs requires surface expression of full-length glycosylated CD133 protein. Within a series of androgen receptor-positive (AR+) human prostate cancer cell lines, CD133+ cells are present at a low frequency, self-renew, express AR, generate phenotypically heterogeneous progeny negative for CD133, and possess an unlimited proliferative capacity, consistent with CD133+ cells being CICs. Unlike normal adult prostate stem cells, prostate CICs are AR+ and do not require functional CD133. This suggests that (a) AR-expressing prostate CICs are derived from a malignantly transformed intermediate cell that acquires "stem-like activity" and not from a malignantly transformed normal stem cell and (b) AR signaling pathways are a therapeutic target for prostate CICs.

Exposure to Brefeldin A promotes initiation of meiosis in murine female germ cells.

Science.gov (United States)

Zhang, Lian-Jun; Chen, Bo; Feng, Xin-Lei; Ma, Hua-Gang; Sun, Li-Lan; Feng, Yan-Min; Liang, Gui-Jin; Cheng, Shun-Feng; Li, Lan; Shen, Wei

2015-01-01

In mammals, ontogenesis starts from a fusion of spermatozoon and oocyte, which are produced by reductive nuclear division of a diploid germ cell in a specialised but complex biological process known as meiosis. However, little is known about the mechanism of meiotic initiation in germ cells, although many factors may be responsible for meiosis both in male and female gonads. In this study, 11.5 days post coitum (dpc) female fetal mouse genital ridges were cultured in vitro with exposure to Brefeldin A (BFA) for 6h, and the changes in meiosis were detected. Synaptonemal-complex analysis implied that BFA played a positive role in meiosis initiation and this hypothesis was confirmed by quantitative PCR of meiosis-specific genes: stimulated by retinoic acid gene 8 (Stra8) and deleted in a zoospermia-like (DAZL). At the same time, mRNA expression of retinoic acid synthetase (Raldh2) and retinoic acid (RA) receptors increased in female gonads with in vitro exposure to BFA. Transplanting genital ridges treated with BFA into the kidney capsule of immunodeficient mice demonstrated that the development capacity of female germ cells was normal, while formation of primordial follicles was seen to be a result of accelerated meiosis after exposure to BFA. In conclusion, the study indicated that BFA stimulated meiosis initiation partly by RA signalling and then promoted the development of follicles.

MGL2 Dermal dendritic cells are sufficient to initiate contact hypersensitivity in vivo.

Directory of Open Access Journals (Sweden)

Yosuke Kumamoto

Full Text Available Dendritic cells (DCs are the most potent antigen-presenting cells in the mammalian immune system. In the skin, epidermal Langerhans cells (LCs and dermal dendritic cells (DDCs survey for invasive pathogens and present antigens to T cells after migration to the cutaneous lymph nodes (LNs. So far, functional and phenotypic differences between these two DC subsets remain unclear due to lack of markers to identify DDCs.In the present report, we demonstrated that macrophage galactose-type C-type lectin (MGL 2 was exclusively expressed in the DDC subset in the skin-to-LN immune system. In the skin, MGL2 was expressed on the majority (about 88% of MHCII(+CD11c(+ cells in the dermis. In the cutaneous LN, MGL2 expression was restricted to B220(-CD8alpha(loCD11b(+CD11c(+MHCII(hi tissue-derived DC. MGL2(+DDC migrated from the dermis into the draining LNs within 24 h after skin sensitization with FITC. Distinct from LCs, MGL2(+DDCs localized near the high endothelial venules in the outer T cell cortex. In FITC-induced contact hypersensitivity (CHS, adoptive transfer of FITC(+MGL2(+DDCs, but not FITC(+MGL2(-DCs into naive mice resulted in the induction of FITC-specific ear swelling, indicating that DDCs played a key role in initiation of immune responses in the skin.These results demonstrated the availability of MGL2 as a novel marker for DDCs and suggested the contribution of MGL2(+ DDCs for initiating CHS.

Inulin isoforms differ by repeated additions of one crystal unit cell

Science.gov (United States)

Cooper, Peter D.; Barclay, Thomas G.; Ginic-Markovic, Milena; Gerson, Andrea R.; Petrovsky, Nikolai

2014-01-01

Inulin isoforms, especially delta inulin, are important biologically as immune activators and clinically as vaccine adjuvants. In exploring action mechanisms, we previously found regular increments in thermal properties of the seven-member inulin isoform series that suggested regular additions of some energetic structural unit. Because the previous isolates carried additional longer chains that masked defining ranges, these were contrasted with new isoform isolates comprising only inulin chain lengths defining that isoform. The new series began with 19 fructose units per chain (alpha-1 inulin), increasing regularly by 6 fructose units per isoform. Thus the ‘energetic unit’ equates to 6 fructose residues per chain. All isoforms showed indistinguishable X-ray diffraction patterns that were also identical with known inulin crystals. We conclude that an ‘energetic unit’ equates to one helix turn of 6 fructose units per chain as found in one unit cell of the inulin crystal. Each isoform chain comprised progressively more helix turns plus one additional fructose and glucose residues per chain. PMID:24528745

Theoretical Analysis of Moving Reference Planes Associated with Unit Cells of Nonreciprocal Lossy Periodic Transmission-Line Structures

Directory of Open Access Journals (Sweden)

S. Lamultree

2017-04-01

Full Text Available This paper presents a theoretical analysis of moving reference planes associated with unit cells of nonreciprocal lossy periodic transmission-line structures (NRLSPTLSs by the equivalent bi-characteristic-impedance transmission line (BCITL model. Applying the BCITL theory, only the equivalent BCITL parameters (characteristic impedances for waves propagating in forward and reverse directions and associated complex propagation constants are of interest. An infinite NRLSPTLS is considered first by shifting a reference position of unit cells along TLs of interest. Then, a semi-infinite terminated NRLSPTLS is investigated in terms of associated load reflection coefficients. It is found that the equivalent BCITL characteristic impedances of the original and shifted unit cells are mathematically related by the bilinear transformation. In addition, the associated load reflection coefficients of both unit cells are mathematically related by the bilinear transformation. However, the equivalent BCITL complex propagation constants remain unchanged. Numerical results are provided to show the validity of the proposed theoretical analysis.

Dasatinib and Doxorubicin Treatment of Sarcoma Initiating Cells: A Possible New Treatment Strategy

DEFF Research Database (Denmark)

Aggerholm-Pedersen, Ninna; Demouth, Christina; Safwat, Akmal

2016-01-01

Background. One of the major challenges affecting sarcoma treatment outcome, particularly that of metastatic disease, is resistance to chemotherapy. Cancer-initiating cells are considered a major contributor to this resistance. Methods. An immortalised nontransformed human stromal (mesenchymal......) stem cell line hMSC-TERT4 and a transformed cell line hMSC-TERT20-CE8, known to form sarcoma-like tumours when implanted in immune-deficient mice, were used as models. Receptor tyrosine kinase (RTK) activation was analysed by RTK arrays and cellular viability after tyrosine kinases inhibitor (TKI...

Solid Oxide Fuel Cells coupled with a biomass gasification unit

Directory of Open Access Journals (Sweden)

Skrzypkiewicz Marek

2016-01-01

Full Text Available A possibility of fuelling a solid oxide fuel cell stack (SOFC with biomass fuels can be realized by coupling a SOFC system with a self-standing gasification unit. Such a solution enables multi-fuel operation, elasticity of the system as well as the increase of the efficiency of small-scale biomass-to-electricity conversion units. A system of this type, consisting of biomass gasification unit, gas purification unit, SOFC stack, anode off-gas afterburner and peripherals was constructed and operated successfully. During the process, biomass fuel (wood chips was gasified with air as gasification agent. The gasifier was capable of converting up to 30 kW of fuel to syngas with efficiencies up to 75%. Syngas leaving the gasification unit is delivered to a medium temperature adsorber for sulphur compounds removal. Steam is added to the purified fuel to maintain steam to carbon ratio higher than 2. The syngas then is passed to a SOFC stack through a fuel preheater. In such a configuration it was possible to operate a commercial 1.3 kW stack within its working regime. Conducted tests confirmed successful operation of a SOFC stack fuelled by biomass-sourced syngas.

THE GERMLINE STEM CELL NICHE UNIT IN MAMMALIAN TESTES

Science.gov (United States)

Oatley, Jon M.; Brinster, Ralph L.

2014-01-01

This review addresses current understanding of the germline stem cell niche unit in mammalian testes. Spermatogenesis is a classic model of tissue-specific stem cell function relying on self-renewal and differentiation of spermatogonial stem cells (SSCs). These fate decisions are influenced by a niche microenvironment composed of a growth factor milieu that is provided by several testis somatic support cell populations. Investigations over the last two decades have identified key determinants of the SSC niche including cytokines that regulate SSC functions and support cells providing these factors, adhesion molecules that influence SSC homing, and developmental heterogeneity of the niche during postnatal aging. Emerging evidence suggests that Sertoli cells are a key support cell population influencing the formation and function of niches by secreting soluble factors and possibly orchestrating contributions of other support cells. Investigations with mice have shown that niche influence on SSC proliferation differs during early postnatal development and adulthood. Moreover, there is mounting evidence of an age-related decline in niche function, which is likely influenced by systemic factors. Defining the attributes of stem cell niches is key to developing methods to utilize these cells for regenerative medicine. The SSC population and associated niche comprise a valuable model system for study that provides fundamental knowledge about the biology of tissue-specific stem cells and their capacity to sustain homeostasis of regenerating tissue lineages. While the stem cell is essential for maintenance of all self-renewing tissues and has received considerable attention, the role of niche cells is at least as important and may prove to be more receptive to modification in regenerative medicine. PMID:22535892

Sonic hedgehog initiates cochlear hair cell regeneration through downregulation of retinoblastoma protein

International Nuclear Information System (INIS)

Lu, Na; Chen, Yan; Wang, Zhengmin; Chen, Guoling; Lin, Qin; Chen, Zheng-Yi; Li, Huawei

2013-01-01

Highlights: ► Shh activation in neonatal cochleae enhances sensory cell proliferation. ► Proliferating supporting cells can transdifferentiate into hair cells. ► Shh promotes proliferation by transiently modulating pRb activity. ► Shh inhibits pRb by inhibiting transcription and increasing phosphorylation of pRb. -- Abstract: Cell cycle re-entry by cochlear supporting cells and/or hair cells is considered one of the best approaches for restoring hearing loss as a result of hair cell damage. To identify mechanisms that can be modulated to initiate cell cycle re-entry and hair cell regeneration, we studied the effect of activating the sonic hedgehog (Shh) pathway. We show that Shh signaling in postnatal rat cochleae damaged by neomycin leads to renewed proliferation of supporting cells and hair cells. Further, proliferating supporting cells are likely to transdifferentiate into hair cells. Shh treatment leads to inhibition of retinoblastoma protein (pRb) by increasing phosphorylated pRb and reducing retinoblastoma gene transcription. This results in upregulation of cyclins B1, D2, and D3, and CDK1. These results suggest that Shh signaling induces cell cycle re-entry in cochlear sensory epithelium and the production of new hair cells, in part by attenuating pRb function. This study provides an additional route to modulate pRb function with important implications in mammalian hair cell regeneration.

Zeroing in on red blood cell unit expiry.

Science.gov (United States)

Ayyalil, Fathima; Irwin, Greg; Ross, Bryony; Manolis, Michael; Enjeti, Anoop K

2017-12-01

Expiry of red blood cell (RBC) units is a significant contributor to wastage of precious voluntary donations. Effective strategies aimed at optimal resource utilization are required to minimize wastage. This retrospective study analyzed the strategic measures implemented to reduce expiry of RBC units in an Australian tertiary regional hospital. The measures, which included inventory rearrangement, effective stock rotation, and the number of emergency courier services required during a 24-month period, were evaluated. There was no wastage of RBC units due to expiry over the 12 months after policy changes. Before these changes, approximately half of RBC wastage (261/511) was due to expiry. The total number of transfusions remained constant in this period and there was no increase in the use of emergency couriers. Policy changes implemented were decreasing the RBC inventory level by one-third and effective stock rotation and using a computerized system to link the transfusion services across the area. Effective stock rotation resulted in a reduction in older blood (>28 days) received in the main laboratory rotated from peripheral hospitals, down from 6%-41% to 0%-2.5%. Age-related expiry of blood products is preventable and can be significantly reduced by improving practices in the pathology service. This study provides proof of principle for "zero tolerance for RBC unit expiry" across a large networked blood banking service. © 2017 The Authors Transfusion published by Wiley Periodicals, Inc. on behalf of AABB.

Implementation of a new blood cooler insert and tracking technology with educational initiatives and its effect on reducing red blood cell wastage.

Science.gov (United States)

Fadeyi, Emmanuel A; Emery, Wanda; Simmons, Julie H; Jones, Mary Rose; Pomper, Gregory J

2017-10-01

The objective was to report a successful implementation of a blood cooler insert and tracking technology with educational initiatives and its effect on reducing red blood cell (RBC) wastage. The blood bank database was used to quantify and categorize total RBC units issued in blood coolers from January 2010 to December 2015 with and without the new inserts throughout the hospital. Radiofrequency identification tags were used with special software to monitor blood cooler tracking. An educational policy on how to handle the coolers was initiated. Data were gathered from the software that provided a real-time location monitoring of the blood coolers with inserts throughout the institution. The implementation of the blood cooler with inserts and tracking device reduced mean yearly RBC wastage by fourfold from 0.64% to 0.17% between 2010 and 2015. The conserved RBCs corresponded to a total cost savings of $167,844 during the 3-year postimplementation period. The implementation of new blood cooler inserts, tracking system, and educational initiatives substantially reduced the mean annual total RBC wastage. The cost to implement this initiative may be small if there is an existing institutional infrastructure to monitor and track hospital equipment into which the blood bank intervention can be adapted when compared to the cost of blood wastage. © 2017 AABB.

Drug-resistant colon cancer cells produce high carcinoembryonic antigen and might not be cancer-initiating cells

Science.gov (United States)

Lee, Hsin-chung; Ling, Qing-Dong; Yu, Wan-Chun; Hung, Chunh-Ming; Kao, Ta-Chun; Huang, Yi-Wei; Higuchi, Akon

2013-01-01

Purpose We evaluated the higher levels of carcinoembryonic antigen (CEA) secreted by the LoVo human colon carcinoma cells in a medium containing anticancer drugs. Drug-resistant LoVo cells were analyzed by subcutaneously xenotransplanting them into mice. The aim of this study was to evaluate whether the drug-resistant cells isolated in this study were cancer-initiating cells, known also as cancer stem cells (CSCs). Methods The production of CEA was investigated in LoVo cells that were cultured with 0–10 mM of anticancer drugs, and we evaluated the increase in CEA production by the LoVo cells that were stimulated by anticancer drug treatment. The expression of several CSC markers in LoVo cells treated with anticancer drugs was also evaluated. Following anticancer drug treatment, LoVo cells were injected subcutaneously into the flanks of severe combined immunodeficiency mice in order to evaluate the CSC fraction. Results Production of CEA by LoVo cells was stimulated by the addition of anticancer drugs. Drug-resistant LoVo cells expressed lower levels of CSC markers, and LoVo cells treated with any of the anticancer drugs tested did not generate tumors within 8 weeks from when the cells were injected subcutaneously into severe combined immunodeficiency mice. These results suggest that the drug-resistant LoVo cells have a smaller population of CSCs than the untreated LoVo cells. Conclusion Production of CEA by LoVo cells can be stimulated by the addition of anticancer drugs. The drug-resistant subpopulation of LoVo colon cancer cells could stimulate the production of CEA, but these cells did not act as CSCs in in vivo tumor generation experiments. PMID:23818760

Unit cell-based computer-aided manufacturing system for tissue engineering

International Nuclear Information System (INIS)

Kang, Hyun-Wook; Park, Jeong Hun; Kang, Tae-Yun; Seol, Young-Joon; Cho, Dong-Woo

2012-01-01

Scaffolds play an important role in the regeneration of artificial tissues or organs. A scaffold is a porous structure with a micro-scale inner architecture in the range of several to several hundreds of micrometers. Therefore, computer-aided construction of scaffolds should provide sophisticated functionality for porous structure design and a tool path generation strategy that can achieve micro-scale architecture. In this study, a new unit cell-based computer-aided manufacturing (CAM) system was developed for the automated design and fabrication of a porous structure with micro-scale inner architecture that can be applied to composite tissue regeneration. The CAM system was developed by first defining a data structure for the computing process of a unit cell representing a single pore structure. Next, an algorithm and software were developed and applied to construct porous structures with a single or multiple pore design using solid freeform fabrication technology and a 3D tooth/spine computer-aided design model. We showed that this system is quite feasible for the design and fabrication of a scaffold for tissue engineering. (paper)

Unit cell-based computer-aided manufacturing system for tissue engineering.

Science.gov (United States)

Kang, Hyun-Wook; Park, Jeong Hun; Kang, Tae-Yun; Seol, Young-Joon; Cho, Dong-Woo

2012-03-01

Scaffolds play an important role in the regeneration of artificial tissues or organs. A scaffold is a porous structure with a micro-scale inner architecture in the range of several to several hundreds of micrometers. Therefore, computer-aided construction of scaffolds should provide sophisticated functionality for porous structure design and a tool path generation strategy that can achieve micro-scale architecture. In this study, a new unit cell-based computer-aided manufacturing (CAM) system was developed for the automated design and fabrication of a porous structure with micro-scale inner architecture that can be applied to composite tissue regeneration. The CAM system was developed by first defining a data structure for the computing process of a unit cell representing a single pore structure. Next, an algorithm and software were developed and applied to construct porous structures with a single or multiple pore design using solid freeform fabrication technology and a 3D tooth/spine computer-aided design model. We showed that this system is quite feasible for the design and fabrication of a scaffold for tissue engineering.

Development of a unit cell model for interim performance assessment of vitrified low level waste disposal

International Nuclear Information System (INIS)

Kline, N.W.

1995-09-01

The unit cell modeling approach has been developed and used in analysis of some design options for a vitrified low level waste disposal facility. The unit cell modeling approach is likely to be useful in interim performance assessment for the facility. The present unit cell model will probably need to be refitted in terms of some model parameters for the latter purpose. Two present disposal facility concepts differ in the length of a capillary barrier proposed to limit effective recharge through the top of the facility. Results of the study summarized herein suggest design of a capillary barrier which can reduce a recharge rate of 0.1 cm/yr by one or two orders of magnitude seems feasible for both concepts. A benchmark comparison of the unit cell model against a full facility model shows comparable predictive accuracy in less than one percent of the computer time. Results suggest that model parameters include capillary barrier performance, inter-canister spacing, rate of moisture withdrawal due to glass corrosion, contaminant inventory, and the well interceptor factor. It is also important that variations of waste form hydraulic parameters suggest that transport through the waste form is dominated by diffusion

International stem cell collaboration: how disparate policies between the United States and the United Kingdom impact research.

Science.gov (United States)

Luo, Jingyuan; Flynn, Jesse M; Solnick, Rachel E; Ecklund, Elaine Howard; Matthews, Kirstin R W

2011-03-08

As the scientific community globalizes, it is increasingly important to understand the effects of international collaboration on the quality and quantity of research produced. While it is generally assumed that international collaboration enhances the quality of research, this phenomenon is not well examined. Stem cell research is unique in that it is both politically charged and a research area that often generates international collaborations, making it an ideal case through which to examine international collaborations. Furthermore, with promising medical applications, the research area is dynamic and responsive to a globalizing science environment. Thus, studying international collaborations in stem cell research elucidates the role of existing international networks in promoting quality research, as well as the effects that disparate national policies might have on research. This study examined the impact of collaboration on publication significance in the United States and the United Kingdom, world leaders in stem cell research with disparate policies. We reviewed publications by US and UK authors from 2008, along with their citation rates and the political factors that may have contributed to the number of international collaborations. The data demonstrated that international collaborations significantly increased an article's impact for UK and US investigators. While this applied to UK authors whether they were corresponding or secondary, this effect was most significant for US authors who were corresponding authors. While the UK exhibited a higher proportion of international publications than the US, this difference was consistent with overall trends in international scientific collaboration. The findings suggested that national stem cell policy differences and regulatory mechanisms driving international stem cell research in the US and UK did not affect the frequency of international collaborations, or even the countries with which the US and UK most

A Notch-dependent molecular circuitry initiates pancreatic endocrine and ductal cell differentiation

DEFF Research Database (Denmark)

Shih, Hung Ping; Kopp, Janel L; Sandhu, Manbir

2012-01-01

necessitates subsequent Sox9 downregulation and evasion from Notch activity via cell-autonomous repression of Sox9 by Ngn3. If high Notch levels are maintained, endocrine progenitors retain Sox9 and undergo ductal fate conversion. Taken together, our findings establish a novel role for Notch in initiating both...

Storage characteristics of multiple-donor pooled red blood cells compared to single-donor red blood cell units.

Science.gov (United States)

Mathur, Aabhas; Chowdhury, Raquibul; Hillyer, Christopher D; Mitchell, W Beau; Shaz, Beth H

2016-12-01

Each unit of blood donated is processed and stored individually resulting in variability in the amount of red blood cells (RBCs) collected, RBC properties, and the 24-hour posttransfusion RBC survivability. As a result, each unit differs in its ability to deliver oxygen and potentially its effects on the recipient. The goal of this study was to investigate the storage of pooled RBCs from multiple donors in comparison to control standard RBC units. Two units of irradiated, leukoreduced RBCs of same ABO, D, E, C, and K antigen phenotype were collected from each of five donors using apheresis. One unit from each donor was pooled in a 2-L bag and remaining units were used as controls. After being pooled, RBCs were separated in five bags and stored at 4°C along with the controls. Quality indexes were measured on Days 2, 14, and 28 for all the units. Adenosine triphosphate assays for both pooled and controls showed a slight decrease from Day 2 to Day 28 (pooled/control from 5.22/5.24 to 4.35/4.33 µmol/g hemoglobin [Hb]). 2,3-Diphosphoglycerate was successfully rejuvenated for all RBC units on Day 28 (pooled 11.46 µmol/g Hb; control 11.86 µmol/g Hb). The results showed a nonsignificant difference between pooled and control units, with a general trend of lower standard deviation for pooled units when compared to controls. Pooled units have reduced unit-to-unit variability. Future exploration of their immunogenicity is required before using pooled units for transfusion. © 2016 AABB.

Fuel Cells in Distributed Power Market Applications in the United States

International Nuclear Information System (INIS)

Rastler, D.

2002-01-01

This paper reviews results from EPRI market analysis, which examined the technical and economic market potential of fuel cells in distributed power markets in the United States. A methodology and approach for developing realistic quantitative estimates of market potential in competitive electricity markets is presented. Market size estimates for phosphoric acid, polymer exchange membrane, high temperature fuel cells (carbonate and solid oxide systems) and ultra-high efficient fuel cell hybrids are estimated. Market potentials are reviewed for fuel cells systems ranging in size from 3 kW up to 20-30 MW in scale and underlying assumptions are provided. The results and implications are discussed in relation to the changing U.S. electric utility market structures. Results will be of value to energy companies and to fuel cell developers seeking to understand revenue sales estimates, market size, and most profitable segments for fuel cells in the competitive US electric markets. (author)

Immunodominant fragments of myelin basic protein initiate T cell-dependent pain

Directory of Open Access Journals (Sweden)

Liu Huaqing

2012-06-01

Full Text Available Abstract Background The myelin sheath provides electrical insulation of mechanosensory Aβ-afferent fibers. Myelin-degrading matrix metalloproteinases (MMPs damage the myelin sheath. The resulting electrical instability of Aβ-fibers is believed to activate the nociceptive circuitry in Aβ-fibers and initiate pain from innocuous tactile stimulation (mechanical allodynia. The precise molecular mechanisms, responsible for the development of this neuropathic pain state after nerve injury (for example, chronic constriction injury, CCI, are not well understood. Methods and results Using mass spectrometry of the whole sciatic nerve proteome followed by bioinformatics analyses, we determined that the pathways, which are classified as the Infectious Disease and T-helper cell signaling, are readily activated in the nerves post-CCI. Inhibition of MMP-9/MMP-2 suppressed CCI-induced mechanical allodynia and concomitant TNF-α and IL-17A expression in nerves. MMP-9 proteolysis of myelin basic protein (MBP generated the MBP84-104 and MBP68-86 digest peptides, which are prominent immunogenic epitopes. In agreement, the endogenous MBP69-86 epitope co-localized with MHCII and MMP-9 in Schwann cells and along the nodes of Ranvier. Administration of either the MBP84-104 or MBP68-86 peptides into the naïve nerve rapidly produced robust mechanical allodynia with a concomitant increase in T cells and MHCII-reactive cell populations at the injection site. As shown by the genome-wide expression profiling, a single intraneural MBP84-104 injection stimulated the inflammatory, immune cell trafficking, and antigen presentation pathways in the injected naïve nerves and the associated spinal cords. Both MBP84-104-induced mechanical allodynia and characteristic pathway activation were remarkably less prominent in the T cell-deficient athymic nude rats. Conclusions These data implicate MBP as a novel mediator of pain. Furthermore, the action of MMPs expressed within 1�

Immunodominant fragments of myelin basic protein initiate T cell-dependent pain.

Science.gov (United States)

Liu, Huaqing; Shiryaev, Sergey A; Chernov, Andrei V; Kim, Youngsoon; Shubayev, Igor; Remacle, Albert G; Baranovskaya, Svetlana; Golubkov, Vladislav S; Strongin, Alex Y; Shubayev, Veronica I

2012-06-07

The myelin sheath provides electrical insulation of mechanosensory Aβ-afferent fibers. Myelin-degrading matrix metalloproteinases (MMPs) damage the myelin sheath. The resulting electrical instability of Aβ-fibers is believed to activate the nociceptive circuitry in Aβ-fibers and initiate pain from innocuous tactile stimulation (mechanical allodynia). The precise molecular mechanisms, responsible for the development of this neuropathic pain state after nerve injury (for example, chronic constriction injury, CCI), are not well understood. Using mass spectrometry of the whole sciatic nerve proteome followed by bioinformatics analyses, we determined that the pathways, which are classified as the Infectious Disease and T-helper cell signaling, are readily activated in the nerves post-CCI. Inhibition of MMP-9/MMP-2 suppressed CCI-induced mechanical allodynia and concomitant TNF-α and IL-17A expression in nerves. MMP-9 proteolysis of myelin basic protein (MBP) generated the MBP84-104 and MBP68-86 digest peptides, which are prominent immunogenic epitopes. In agreement, the endogenous MBP69-86 epitope co-localized with MHCII and MMP-9 in Schwann cells and along the nodes of Ranvier. Administration of either the MBP84-104 or MBP68-86 peptides into the naïve nerve rapidly produced robust mechanical allodynia with a concomitant increase in T cells and MHCII-reactive cell populations at the injection site. As shown by the genome-wide expression profiling, a single intraneural MBP84-104 injection stimulated the inflammatory, immune cell trafficking, and antigen presentation pathways in the injected naïve nerves and the associated spinal cords. Both MBP84-104-induced mechanical allodynia and characteristic pathway activation were remarkably less prominent in the T cell-deficient athymic nude rats. These data implicate MBP as a novel mediator of pain. Furthermore, the action of MMPs expressed within 1 day post-injury is critical to the generation of tactile allodynia

Initial assessment of jaundice in otherwise healthy infants--a comparison of methods in two postnatal units.

LENUS (Irish Health Repository)

Allen, N M

2012-02-01

Transcutaneous bilirubin (TcB) has the potential to reduce total serum bilirubin (TS) sampling. The principal aim of this study was to determine and compare the number of initial TSB samples (TSBs) in two postnatal units (hospitals A & B) whereby hospital A used TcB and hospital B did not. A secondary aim was to determine the clinical factors that led to initial TSBs exceeding exchange transfusion level in both hospitals. Results demonstrated both hospitals had similar populations and patient numbers following selection criteria. 1645 neonates (10.4%) had one or more TSBs performed in hospital A, versus 2373 neonates (15.1%) in hospital B (p < 0.01). Fourteen neonates in hospital A and 3 neonates in hospital B had initial TSBs above exchange transfusion level. For neonates with TSBs above exchange, preventable factors related to earlier testing and follow up. In routine clinical practice, TcB is associated with a significantly reduced number of TSB measurements. TSB levels above exchange transfusion are linked to preventable factors, in otherwise healthy neonates.

Cell-autonomous intracellular androgen receptor signaling drives the growth of human prostate cancer initiating cells.

Science.gov (United States)

Vander Griend, Donald J; D'Antonio, Jason; Gurel, Bora; Antony, Lizamma; Demarzo, Angelo M; Isaacs, John T

2010-01-01

The lethality of prostate cancer is due to the continuous growth of cancer initiating cells (CICs) which are often stimulated by androgen receptor (AR) signaling. However, the underlying molecular mechanism(s) for such AR-mediated growth stimulation are not fully understood. Such mechanisms may involve cancer cell-dependent induction of tumor stromal cells to produce paracrine growth factors or could involve cancer cell autonomous autocrine and/or intracellular AR signaling pathways. We utilized clinical samples, animal models and a series of AR-positive human prostate cancer cell lines to evaluate AR-mediated growth stimulation of prostate CICs. The present studies document that stromal AR expression is not required for prostate cancer growth, since tumor stroma surrounding AR-positive human prostate cancer metastases (N = 127) are characteristically AR-negative. This lack of a requirement for AR expression in tumor stromal cells is also documented by the fact that human AR-positive prostate cancer cells grow equally well when xenografted in wild-type versus AR-null nude mice. AR-dependent growth stimulation was documented to involve secretion, extracellular binding, and signaling by autocrine growth factors. Orthotopic xenograft animal studies documented that the cellautonomous autocrine growth factors which stimulate prostate CIC growth are not the andromedins secreted by normal prostate stromal cells. Such cell autonomous and extracellular autocrine signaling is necessary but not sufficient for the optimal growth of prostate CICs based upon the response to anti-androgen plus/or minus preconditioned media. AR-induced growth stimulation of human prostate CICs requires AR-dependent intracellular pathways. The identification of such AR-dependent intracellular pathways offers new leads for the development of effective therapies for prostate cancer. (c) 2009 Wiley-Liss, Inc.

Transcription of ribosomal RNA genes is initiated in the third cell cycle of bovine embryos

DEFF Research Database (Denmark)

Jakobsen, Anne Sørig; Avery, Birthe; Dieleman, Steph J.

2006-01-01

Transcription from the embryos own ribosomal genes is initiated in most species at the same time as the maternal-embryonic transition. Recently data have indicated that a minor activation may take place during the third embryonic cell cycle in the bovine, one cell cycle before the major activation...

Sonic hedgehog initiates cochlear hair cell regeneration through downregulation of retinoblastoma protein

Energy Technology Data Exchange (ETDEWEB)

Lu, Na [Otology Skull Base Surgery Department, Hearing Research Institute, Eye and ENT Hospital of Shanghai Medical School, Fudan University, Shanghai 200031 (China); Department of Otolaryngology and Program in Neuroscience, Harvard Medical School and Eaton Peabody Laboratory, Massachusetts Eye and Ear Infirmary, Boston, MA 02114 (United States); Chen, Yan [Central Laboratory, Hearing Research Institute, Eye and ENT Hospital of Shanghai Medical School, Fudan University, Shanghai 200031 (China); Wang, Zhengmin [Otology Skull Base Surgery Department, Hearing Research Institute, Eye and ENT Hospital of Shanghai Medical School, Fudan University, Shanghai 200031 (China); Institute of Biomedical Sciences, Fudan University, Shanghai 200032 (China); Chen, Guoling [Otology Skull Base Surgery Department, Hearing Research Institute, Eye and ENT Hospital of Shanghai Medical School, Fudan University, Shanghai 200031 (China); Lin, Qin [Otology Skull Base Surgery Department, Hearing Research Institute, Eye and ENT Hospital of Shanghai Medical School, Fudan University, Shanghai 200031 (China); Department of Otolaryngology, First Affiliated Hospital of Fujian Medical University, Otolaryngology Institute of Fujian Province, Fuzhou (China); Chen, Zheng-Yi, E-mail: Zheng-yi_chen@meei.harvard.edu [Department of Otolaryngology and Program in Neuroscience, Harvard Medical School and Eaton Peabody Laboratory, Massachusetts Eye and Ear Infirmary, Boston, MA 02114 (United States); Li, Huawei, E-mail: hwli@shmu.edu.cn [Otology Skull Base Surgery Department, Hearing Research Institute, Eye and ENT Hospital of Shanghai Medical School, Fudan University, Shanghai 200031 (China); Institute of Biomedical Sciences, Fudan University, Shanghai 200032 (China)

2013-01-11

Highlights: Black-Right-Pointing-Pointer Shh activation in neonatal cochleae enhances sensory cell proliferation. Black-Right-Pointing-Pointer Proliferating supporting cells can transdifferentiate into hair cells. Black-Right-Pointing-Pointer Shh promotes proliferation by transiently modulating pRb activity. Black-Right-Pointing-Pointer Shh inhibits pRb by inhibiting transcription and increasing phosphorylation of pRb. -- Abstract: Cell cycle re-entry by cochlear supporting cells and/or hair cells is considered one of the best approaches for restoring hearing loss as a result of hair cell damage. To identify mechanisms that can be modulated to initiate cell cycle re-entry and hair cell regeneration, we studied the effect of activating the sonic hedgehog (Shh) pathway. We show that Shh signaling in postnatal rat cochleae damaged by neomycin leads to renewed proliferation of supporting cells and hair cells. Further, proliferating supporting cells are likely to transdifferentiate into hair cells. Shh treatment leads to inhibition of retinoblastoma protein (pRb) by increasing phosphorylated pRb and reducing retinoblastoma gene transcription. This results in upregulation of cyclins B1, D2, and D3, and CDK1. These results suggest that Shh signaling induces cell cycle re-entry in cochlear sensory epithelium and the production of new hair cells, in part by attenuating pRb function. This study provides an additional route to modulate pRb function with important implications in mammalian hair cell regeneration.

Transition zone cells reach G2 phase before initiating elongation in maize root apex

Directory of Open Access Journals (Sweden)

M. Victoria Alarcón

2017-06-01

Full Text Available Root elongation requires cell divisions in the meristematic zone and cell elongation in the elongation zone. The boundary between dividing and elongating cells is called the transition zone. In the meristem zone, initial cells are continuously dividing, but on the basal side of the meristem cells exit the meristem through the transition zone and enter in the elongation zone, where they stop division and rapidly elongate. Throughout this journey cells are accompanied by changes in cell cycle progression. Flow cytometry analysis showed that meristematic cells are in cycle, but exit when they enter the elongation zone. In addition, the percentage of cells in G2 phase (4C strongly increased from the meristem to the elongation zone. However, we did not observe remarkable changes in the percentage of cells in cell cycle phases along the entire elongation zone. These results suggest that meristematic cells in maize root apex stop the cell cycle in G2 phase after leaving the meristem.

Relation between both oxidative and metabolic-osmotic cell damages and initial injury severity in bombing casualties

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Vučeljić Marina

2006-01-01

Full Text Available Background/Aim. We have recently reported the development of oxidative cell damages in bombing casualties within a very early period after the initial injury. The aim of this study, was to investigate malondialdehyde (MDA, as an indicator of lipid peroxidation, and osmolal gap (OG, as a good indicator of metabolic cell damages and to assess their relationship with the initial severity of the injury in bombing casualties. Methods. The study included the males (n = 52, injured during the bombing with the Injury Severity Score (ISS ranging from 3 to 66. The whole group of casualties was devided into a group of less severely (ISS < 25, n = 24 and a group of severely (ISS ≥ 26, n = 28 injured males. The uninjured volunteers (n = 10 were the controls. Osmolality, MDA, sodium, glucose, urea, creatinine, total bilirubin and total protein levels were measured in the venous blood, sampled daily, within a ten-day period. Results. In both groups of casualties, MDA and OG levels increased, total protein levels decreased, while other parameters were within the control limits. MDA alterations correlated with ISS (r = 0.414, p < 0.01, while a statistically significant correlation between OG and ISS was not obtained. Interestingly, in spite of some differences in MDA and OG trends, at the end of the examined period they were at the similar level in both groups. Conclusion. The initial oxidative damages of the cellular membrane with intracellular metabolic disorders contributed to the gradual development of metabolic-osmotic damages of cells, which, consequently caused the OG increase. In the bombing casualties, oxidative cell damages were dependent on the initial injury severity, while metabolic-osmotic cell damages were not.

United Kingdom evidence on the behaviour of the beta or systematic risk of initial public offerings

OpenAIRE

Qian, Yi

2012-01-01

This study examines the beta or systematic risk of initial public offerings using a sample of newly issued stocks in the United Kingdom market. The findings are threefold. First, the beta risk estimation is found to decline over time. It corresponds with the differential information model which predicts that the risk of low information is high with uncertainty around it and will decline as the quantity of information increases. The quantity of information, in this case, is represented by time...

Monitoring the initiation and kinetics of human dendritic cell-induced polarization of autologous naive CD4+ T cells.

Directory of Open Access Journals (Sweden)

Tammy Oth

Full Text Available A crucial step in generating de novo immune responses is the polarization of naive cognate CD4+ T cells by pathogen-triggered dendritic cells (DC. In the human setting, standardized DC-dependent systems are lacking to study molecular events during the initiation of a naive CD4+ T cell response. We developed a TCR-restricted assay to compare different pathogen-triggered human DC for their capacities to instruct functional differentiation of autologous, naive CD4+ T cells. We demonstrated that this methodology can be applied to compare differently matured DC in terms of kinetics, direction, and magnitude of the naive CD4+ T cell response. Furthermore, we showed the applicability of this assay to study the T cell polarizing capacity of low-frequency blood-derived DC populations directly isolated ex vivo. This methodology for addressing APC-dependent instruction of naive CD4+ T cells in a human autologous setting will provide researchers with a valuable tool to gain more insight into molecular mechanisms occurring in the early phase of T cell polarization. In addition, it may also allow the study of pharmacological agents on DC-dependent T cell polarization in the human system.

Will initiatives to promote hydroelectricity consumption be effective? Evidence from univariate and panel LM unit root tests with structural breaks

International Nuclear Information System (INIS)

Lean, Hooi Hooi; Smyth, Russell

2014-01-01

This paper examines whether initiatives to promote hydroelectricity consumption are likely to be effective by applying univariate and panel Lagrange Multiplier (LM) unit root tests to hydroelectricity consumption in 55 countries over the period 1965–2011. We find that for the panel, as well as about four-fifths of individual countries, that hydroelectricity consumption is stationary. This result implies that shocks to hydroelectricity consumption in most countries will only result in temporary deviations from the long-run growth path. An important consequence of this finding is that initiatives designed to have permanent positive effects on hydroelectricity consumption, such as large-scale dam construction, are unlikely to be effective in increasing the share of hydroelectricity, relative to consumption of fossil fuels. - Highlights: • Applies unit root tests to hydroelectricity consumption. • Hydroelectricity consumption is stationary. • Shocks to hydroelectricity consumption result in temporary deviations from the long-run growth path

Transformation assay in Bhas 42 cells: a model using initiated cells to study mechanisms of carcinogenesis and predict carcinogenic potential of chemicals.

Science.gov (United States)

Sasaki, Kiyoshi; Umeda, Makoto; Sakai, Ayako; Yamazaki, Shojiro; Tanaka, Noriho

2015-01-01

Transformation assays using cultured cells have been applied to the study of carcinogenesis. Although various cell systems exist, few cell types such as BALB/c 3T3 subclones and Syrian hamster embryo cells have been used to study chemically induced two-stage carcinogenesis. Bhas 42 cells were established as a clone by the transfection with the v-Ha-ras gene into mouse BALB/c 3T3 A31-1-1 cells and their subsequent selection based on their sensitivity to 12-O-tetradecanoylphorbol-13-acetate. Using Bhas 42 cells, transformed foci were induced by the treatment with nongenotoxic carcinogens, most of which act as tumor promoters. Therefore, Bhas 42 cells were considered to be a model of initiated cells. Subsequently, not only nongenotoxic carcinogens but also genotoxic carcinogens, most of which act as tumor initiators, were found to induce transformed foci by the modification of the protocol. Furthermore, transformation of Bhas 42 cells was induced by the transfection with genes of oncogenic potential. We interpret this high sensitivity of Bhas 42 cells to various types of carcinogenic stimuli to be related to the multistage model of carcinogenesis, as the transfection of v-Ha-ras gene further advances the parental BALB/c 3T3 A31-1-1 cells toward higher transforming potential. Thus, we propose that Bhas 42 cells are a novel and sensitive cell line for the analysis of carcinogenesis and can be used for the detection of not only carcinogenic substances but also gene alterations related to oncogenesis. This review will address characteristics of Bhas 42 cells, the transformation assay protocol, validation studies, and the various chemicals tested in this assay.

ER stress is the initial response to polyglutamine toxicity in PC12 cells

International Nuclear Information System (INIS)

Nakayama, Hitoshi; Hamada, Masashi; Fujikake, Nobuhiro; Nagai, Yoshitaka; Zhao, Jing; Hatano, Osamu; Shimoke, Koji; Isosaki, Minoru; Yoshizumi, Masanori; Ikeuchi, Toshihiko

2008-01-01

Persistent endoplasmic reticulum (ER) stress and impairment of the ubiquitin-proteasome system (UPS) cause neuronal cell death. However, the relationship between these two phenomena remains controversial. In our current study, we have utilized an expanded polyglutamine fusion protein (polyQ81) expression system in PC12 cells to further examine the involvement of ER stress and UPS impairment in cell death. The expression of polyQ81-induced ER stress and cell death. PolyQ81 also induced the activation of c-Jun N-terminal kinase (JNK) and caspase-3 and an increase in polyubiquitin immunoreactivity, suggesting UPS impairment. ER stress was induced prior to the accumulation of polyubiquitinated proteins. Low doses of lactacystin had almost similar effects on cell viability and on the activation of JNK and caspase-3 between normal cells and polyQ81-expressing cells. These results suggest that ER stress mediates polyglutamine toxicity prior to UPS impairment during the initial stages of these toxic effects.

Global initiatives to tackle organ trafficking and transplant tourism.

Science.gov (United States)

Bagheri, Alireza; Delmonico, Francis L

2013-11-01

The increasing gap between organ supply and demand has opened the door for illegal organ sale, trafficking of human organs, tissues and cells, as well as transplant tourism. Currently, underprivileged and vulnerable populations in resource-poor countries are a major source of organs for rich patient-tourists who can afford to purchase organs at home or abroad. This paper presents a summary of international initiatives, such as World Health Organization's Principle Guidelines, The Declaration of Istanbul, Asian Task Force Recommendations, as well as UNESCO's and the United Nation's initiatives against trafficking of human organs, tissues, cells, and transplant tourism. Beyond the summary, it calls for more practical measures to be taken to implement the existing guidelines and recommendations, in order to prevent exploitation of the poor as organ providers. The paper suggests that an international legally binding agreement in criminalizing organ trafficking would be a step forward to bring a change in the global picture of organ trafficking and transplant tourism.

MAPK13 is preferentially expressed in gynecological cancer stem cells and has a role in the tumor-initiation

Energy Technology Data Exchange (ETDEWEB)

Yasuda, Kazuyo [Department of Pathology, Sapporo Medical University School of Medicine, South-1 West-17, Chuo-Ku, Sapporo, 060-8556 (Japan); Hirohashi, Yoshihiko, E-mail: hirohash@sapmed.ac.jp [Department of Pathology, Sapporo Medical University School of Medicine, South-1 West-17, Chuo-Ku, Sapporo, 060-8556 (Japan); Kuroda, Takafumi [Department of Obstetrics and Gynecology, Sapporo Medical University School of Medicine, South-1 West-17, Chuo-Ku, Sapporo, 060-8556 (Japan); Takaya, Akari; Kubo, Terufumi; Kanaseki, Takayuki; Tsukahara, Tomohide [Department of Pathology, Sapporo Medical University School of Medicine, South-1 West-17, Chuo-Ku, Sapporo, 060-8556 (Japan); Hasegawa, Tadashi [Department of Surgical Pathology, Sapporo Medical University School of Medicine, South-1 West-17, Chuo-Ku, Sapporo, 060-8556 (Japan); Saito, Tsuyoshi [Department of Obstetrics and Gynecology, Sapporo Medical University School of Medicine, South-1 West-17, Chuo-Ku, Sapporo, 060-8556 (Japan); Sato, Noriyuki [Department of Pathology, Sapporo Medical University School of Medicine, South-1 West-17, Chuo-Ku, Sapporo, 060-8556 (Japan); Torigoe, Toshihiko, E-mail: torigoe@sapmed.ac.jp [Department of Pathology, Sapporo Medical University School of Medicine, South-1 West-17, Chuo-Ku, Sapporo, 060-8556 (Japan)

2016-04-15

Cancer stem-like cells (CSCs)/cancer-initiating cells (CICs) are defined as small subpopulation of cancer cells that are endowed with higher tumor-initiating ability. CSCs/CICs are resistant to standard cancer therapies including chemotherapy and radiotherapy, and they are thus thought to be responsible for cancer recurrence and metastasis. Therefore, elucidation of molecular mechanisms of CSCs/CICs is essential to cure cancer. In this study, we analyzed the gene expression profiles of gynecological CSCs/CICs isolated as aldehyde dehydrogenase high (ALDH{sup high}) cells, and found that MAPK13, PTTG1IP, CAPN1 and UBQLN2 were preferentially expressed in CSCs/CICs. MAPK13 is expressed in uterine, ovary, stomach, colon, liver and kidney cancer tissues at higher levels compared with adjacent normal tissues. MAPK13 gene knockdown using siRNA reduced the ALDH{sup high} population and abrogated the tumor-initiating ability. These results indicate that MAPK13 is expressed in gynecological CSCs/CICs and has roles in the maintenance of CSCs/CICs and tumor-initiating ability, and MAPK13 might be a novel molecular target for treatment-resistant CSCs/CICs.

Unit-cell refinement from powder diffraction scans

International Nuclear Information System (INIS)

Pawley, G.S.

1981-01-01

A procedure for the refinement of the crystal unit cell from a powder diffraction scan is presented. In this procedure knowledge of the crystal structure is not required, and at the end of the refinement a list of indexed intensities is produced. This list may well be usable as the starting point for the application of direct methods. The problems of least-squares ill-conditioning due to overlapping reflections are overcome by constraints. An example using decafluorocyclohexene, C 6 F 10 , shows the quality of fit obtained in a case which may even be a false minimum. The method should become more relevant as powder scans of improved resolution become available, through the use of pulsed neutron sources. (Auth.)

Unit-cell design for two-dimensional phase-field simulation of microstructure evolution in single-crystal Ni-based superalloys during solidification

Directory of Open Access Journals (Sweden)

Dongjia Cao

2017-12-01

Full Text Available Phase-field simulation serves as an effective tool for quantitative characterization of microstructure evolution in single-crystal Ni-based superalloys during solidification nowadays. The classic unit cell is either limited to γ dendrites along crystal orientation or too ideal to cover complex morphologies for γ dendrites. An attempt to design the unit cell for two-dimensional (2-D phase-field simulations of microstructure evolution in single-crystal Ni-based superalloys during solidification was thus performed by using the MICRESS (MICRostructure Evolution Simulation Software in the framework of the multi-phase-field (MPF model, and demonstrated in a commercial TMS-113 superalloy. The coupling to CALPHAD (CALculation of PHAse Diagram thermodynamic database was realized via the TQ interface and the experimental diffusion coefficients were utilized in the simulation. Firstly, the classic unit cell with a single γ dendrite along crystal orientation was employed for the phase-field simulation in order to reproduce the microstructure features. Then, such simple unit cell was extended into the cases with two other different crystal orientations, i.e., and . Thirdly, for crystal orientations, the effect of γ dendritic orientations and unit cell sizes on microstructure and microsegregation was comprehensively studied, from which a new unit cell with multiple γ dendrites was proposed. The phase-field simulation with the newly proposed unit cell was further performed in the TMS-113 superalloy, and the microstructure features including the competitive growth of γ dendrites, microsegregation of different solutes and distribution of γ′ grains, can be nicely reproduced.

Composite Bipolar Plate for Unitized Fuel Cell/Electrolyzer Systems

Science.gov (United States)

Mittelsteadt, Cortney K.; Braff, William

2009-01-01

In a substantial improvement over present alkaline systems, an advanced hybrid bipolar plate for a unitized fuel cell/electrolyzer has been developed. This design, which operates on pure feed streams (H2/O2 and water, respectively) consists of a porous metallic foil filled with a polymer that has very high water transport properties. Combined with a second metallic plate, the pore-filled metallic plates form a bipolar plate with an empty cavity in the center.

The effect of an asynchronous population of cells on the initial slope of dose-effect curves

International Nuclear Information System (INIS)

Chadwick, K.H.; Leenhouts, H.P.

1975-01-01

The molecular theory of cell survival gives an equation S = exp [ -p(αD + β D 2 )] which can be used to analyse dose-effect curves for synchronized cells. The variation in the coefficients α and β through the cell cycle has been found to be consistent for the different radiation types and is compatible with the induction of DNA double-strand breaks which is assumed in the theory to be the mechanism which is responsible for the biological effect. The theory predicts that low-LET radiation will have an initial slope, given by the coefficient α, and the consistency of the analysis of synchronized cell survival substantiates this prediction. In the molecular theory the induction of mutations has also been proposed to arise from DNA double-strand breaks and to be represented by the equation M = 1 - exp [-q(αD + β D 2 )]. This implies that at low doses of low-LET radiation the radiobiological effect will be linear with dose and that high-dose results may be analysed to provide estimates of the radiosensitivity of cells to low doses of radiation for radiological protection purposes. In an asynchronous population of cells it is possible that a small proportion of very radiosensitive cells can lead to significant deviations from this straightforward analysis. This 'Oftedal effect' is applied using the molecular theory to give a general theoretical relationship between the induction of mutations and cell survival. The theoretical relationship is compared with experimental data available from the literature. It is concluded that the initial slope of a mutation or cancer induction curve may be more relevant to the determination of the radiation sensitivity at low doses than the initial slope of a survival curve. (author)

Trends in US minority red blood cell unit donations.

Science.gov (United States)

Yazer, Mark H; Delaney, Meghan; Germain, Marc; Karafin, Matthew S; Sayers, Merlyn; Vassallo, Ralph; Ziman, Alyssa; Shaz, Beth

2017-05-01

To provide the appropriately diverse blood supply necessary to support alloimmunized and chronically transfused patients, minority donation recruitment programs have been implemented. This study investigated temporal changes in minority red blood cell (RBC) donation patterns in the United States. Data on donor race and ethnicity from 2006 through 2015, including the number of unique donors, collections, RBCs successfully donated, and average annual number of RBC donations per donor (donor fraction), were collected from eight US blood collectors. Minority donors were stratified into the following groups: Asian, black or African American, Hispanic or Latino, Native Indian or Alaska Native, Native Hawaiian or other Pacific Islander, white, multiracial/other, and no answer/not sure. Over the 10-year period, white donors annually constituted the majority of unique donors (range, 70.7%-73.9%), had the greatest proportion of collections (range, 76.1%-79.8%), and donated the greatest proportion of RBC units (range, 76.3%-80.2%). These donors also had the highest annual donor fraction (range, 1.82-1.91 units per donor). Black or African American donors annually constituted between 4.9 and 5.2% of all donors during the study period and donated between 4.0 and 4.3% of all RBC units. Linear regression analysis revealed decreasing numbers of donors, collections, and donated RBC units from white donors over time. Although the US population has diversified, and minority recruitment programs have been implemented, white donors constitute the majority of RBC donors and donations. Focused and effective efforts are needed to increase the proportion of minority donors. © 2017 AABB.

Quasi bound states in the continuum with few unit cells of photonic crystal slab

DEFF Research Database (Denmark)

Taghizadeh, Alireza; Chung, Il-Sug

2017-01-01

cell structures. They are explained by a viewpoint of BICs originating from the tight-binding of individual resonances of each unit cell as in semiconductors. Combined with a reciprocal-space matching technique, the microcavities based on quasi-BICs can achieve a Q-factor as high as defect-based Ph...

Systems Analysis Initiated for All-Electric Aircraft Propulsion

Science.gov (United States)

Kohout, Lisa L.

2003-01-01

A multidisciplinary effort is underway at the NASA Glenn Research Center to develop concepts for revolutionary, nontraditional fuel cell power and propulsion systems for aircraft applications. There is a growing interest in the use of fuel cells as a power source for electric propulsion as well as an auxiliary power unit to substantially reduce or eliminate environmentally harmful emissions. A systems analysis effort was initiated to assess potential concepts in an effort to identify those configurations with the highest payoff potential. Among the technologies under consideration are advanced proton exchange membrane (PEM) and solid oxide fuel cells, alternative fuels and fuel processing, and fuel storage. Prior to this effort, the majority of fuel cell analysis done at Glenn was done for space applications. Because of this, a new suite of models was developed. These models include the hydrogen-air PEM fuel cell; internal reforming solid oxide fuel cell; balance-of-plant components (compressor, humidifier, separator, and heat exchangers); compressed gas, cryogenic, and liquid fuel storage tanks; and gas turbine/generator models for hybrid system applications. Initial mass, volume, and performance estimates of a variety of PEM systems operating on hydrogen and reformate have been completed for a baseline general aviation aircraft. Solid oxide/turbine hybrid systems are being analyzed. In conjunction with the analysis efforts, a joint effort has been initiated with Glenn s Computer Services Division to integrate fuel cell stack and component models with the visualization environment that supports the GRUVE lab, Glenn s virtual reality facility. The objective of this work is to provide an environment to assist engineers in the integration of fuel cell propulsion systems into aircraft and provide a better understanding of the interaction between system components and the resulting effect on the overall design and performance of the aircraft. Initially, three

Characteristics of CD8+ T cell subsets in Chinese patients with chronic HIV infection during initial ART.

Science.gov (United States)

Jiao, Yanmei; Hua, Wei; Zhang, Tong; Zhang, Yonghong; Ji, Yunxia; Zhang, Hongwei; Wu, Hao

2011-03-25

CD8+ T cells may play an important role in protecting against HIV. However, the changes of CD8+ T cell subsets during early period of ART have not been fully studied. Twenty-one asymptomatic treatment-naive HIV-infected patients with CD4 T+ cells less than 350 cells/μl were enrolled in the study. Naïve, central memory(CM), effective memory(EM) and terminally differentiated effector (EMRA) CD8+ cell subsets and their activation and proliferation subsets were evaluated in blood samples collected at base line, and week 2, 4, 8 and 12 of ART. The total CD8+ T cells declined and the Naïve and CM subsets had a tendency of increase. Activation levels of all CD8+ T cell subsets except EMRA subset decreased after ART. However, proliferation levels of total CD8+ T cells, EMRA, EM and CM subsets increased at the first 4 weeks of ART, then decreased. Proliferation level of the naïve cells decreased after ART. The changes of CD8+ T cell subsets during initial ART are complex. Our results display a complete phenotypical picture of CD8+ cell subsets during initial ART and provide insights for understanding of immune status during ART.

Characteristics of CD8+ T cell subsets in Chinese patients with chronic HIV infection during initial ART

Directory of Open Access Journals (Sweden)

Zhang Hongwei

2011-03-01

Full Text Available Abstract Background CD8+ T cells may play an important role in protecting against HIV. However, the changes of CD8+ T cell subsets during early period of ART have not been fully studied. Methods Twenty-one asymptomatic treatment-naive HIV-infected patients with CD4 T+ cells less than 350 cells/μl were enrolled in the study. Naïve, central memory(CM, effective memory(EM and terminally differentiated effector (EMRA CD8+ cell subsets and their activation and proliferation subsets were evaluated in blood samples collected at base line, and week 2, 4, 8 and 12 of ART. Results The total CD8+ T cells declined and the Naïve and CM subsets had a tendency of increase. Activation levels of all CD8+ T cell subsets except EMRA subset decreased after ART. However, proliferation levels of total CD8+ T cells, EMRA, EM and CM subsets increased at the first 4 weeks of ART, then decreased. Proliferation level of the naïve cells decreased after ART. Conclusion The changes of CD8+ T cell subsets during initial ART are complex. Our results display a complete phenotypical picture of CD8+ cell subsets during initial ART and provide insights for understanding of immune status during ART.

The Daniell Cell, Ohm's Law and the Emergence of the International System of Units

OpenAIRE

Jayson, Joel S.

2015-01-01

Telegraphy originated in the 1830s and 40s and flourished in the following decades, but with a patchwork of electrical standards. Electromotive force was for the most part measured in units of the predominant Daniell cell. Each company had their own resistance standard. In 1862 the British Association for the Advancement of Science formed a committee to address this situation. By 1873 they had given definition to the electromagnetic system of units (emu) and defined the practical units of the...

Diffusion of single Au, Ag and Cu atoms inside Si(111)-(7 × 7) half unit cells: A comparative study

Energy Technology Data Exchange (ETDEWEB)

Liu, Qin [Department of Physics, Southern University of Science and Technology, Shenzhen, Guangdong 518055 (China); Department of Physics, The Chinese University of Hong Kong, Shatin, New Territory, Hong Kong (China); Science and Technology on Surface Physics and Chemistry Laboratory, Mianyang, Sichuan 621908 (China); Fu, Qiang [Institut für Physik and IRIS Adlershof, Humboldt-Universität zu Berlin, Zum Großen Windkanal 6, 12489 Berlin (Germany); Shao, Xiji; Ma, Xuhang; Wu, Xuefeng [Department of Physics, Southern University of Science and Technology, Shenzhen, Guangdong 518055 (China); Wang, Kedong, E-mail: wangkd@sustc.edu.cn [Department of Physics, Southern University of Science and Technology, Shenzhen, Guangdong 518055 (China); Xiao, Xudong, E-mail: xdxiao@phy.cuhk.edu.hk [Department of Physics, The Chinese University of Hong Kong, Shatin, New Territory, Hong Kong (China)

2017-04-15

Highlights: • Diffusions of Au, Ag and Cu atoms in the half unit cells of Si(111)-(7×7) have been studied by using a STM-based I-t method. • Despite their similar absorption sites, the diffusion dynamics show obvious differences between Ag and the other two. • Theoretical calculations suggest that different potential energy profiles are responsible for the observed differences. - Abstract: The diffusion behaviors of single Au, Ag and Cu atoms on Si(111)-(7 × 7) half unit cells have been investigated via combining scanning tunneling microscopy and first-principles calculations. Despite the similar adsorption sites between both half unit cells among these elements, the diffusion dynamics show obvious differences between Ag and the other two. Although obvious asymmetry has been found in the diffusion behaviors of Au and Cu atoms in two half unit cells of Si(111)-(7 × 7), the asymmetry behaves in a way different from that of Ag atoms and no dual-time character has been observed for the diffusions of Au and Cu in both half unit cells. Theoretical calculations suggest a different potential energy profile caused by the stronger hybridization between d states of Au (Cu) and Si states make the concept of basin useless for the diffusion of Au and Cu atoms inside the half unit cells of Si(111)-(7 × 7).

Flow field measurements in the cell culture unit

Science.gov (United States)

Walker, Stephen; Wilder, Mike; Dimanlig, Arsenio; Jagger, Justin; Searby, Nancy

2002-01-01

The cell culture unit (CCU) is being designed to support cell growth for long-duration life science experiments on the International Space Station (ISS). The CCU is a perfused loop system that provides a fluid environment for controlled cell growth experiments within cell specimen chambers (CSCs), and is intended to accommodate diverse cell specimen types. Many of the functional requirements depend on the fluid flow field within the CSC (e.g., feeding and gas management). A design goal of the CCU is to match, within experimental limits, all environmental conditions, other than the effects of gravity on the cells, whether the hardware is in microgravity ( micro g), normal Earth gravity, or up to 2g on the ISS centrifuge. In order to achieve this goal, two steps are being taken. The first step is to characterize the environmental conditions of current 1g cell biology experiments being performed in laboratories using ground-based hardware. The second step is to ensure that the design of the CCU allows the fluid flow conditions found in 1g to be replicated from microgravity up to 2g. The techniques that are being used to take these steps include flow visualization, particle image velocimetry (PIV), and computational fluid dynamics (CFD). Flow visualization using the injection of dye has been used to gain a global perspective of the characteristics of the CSC flow field. To characterize laboratory cell culture conditions, PIV is being used to determine the flow field parameters of cell suspension cultures grown in Erlenmeyer flasks on orbital shakers. These measured parameters will be compared to PIV measurements in the CSCs to ensure that the flow field that cells encounter in CSCs is within the bounds determined for typical laboratory experiments. Using CFD, a detailed simulation is being developed to predict the flow field within the CSC for a wide variety of flow conditions, including microgravity environments. Results from all these measurements and analyses of the

Replacement of the moderator cell unit of JRR-3's cold neutron source facility

International Nuclear Information System (INIS)

Hazawa, Tomoya; Nagahori, Kazuhisa; Kusunoki, Tsuyoshi

2006-10-01

The moderator cell of the JRR-3's cold neutron source (CNS) facility, converts thermal neutrons into cold neutrons by passing through liquid cold hydrogen. The cold neutrons are used for material and life science research such as the neutron scattering. The CNS has been operated since the start of JRR-3's in 1990. The moderator cell containing liquid hydrogen is made of stainless steel. The material irradiation lifetime is limited to 7 years due to irradiation brittleness. The first replacement was done by using a spare part made in France. This replacement work of 2006 was carried out by using the domestic moderator cell unit. The following technologies were developed for the moderator cell unit production. 1) Technical development of black treatment on moderator cell surface to increase radiation heat. 2) Development of bending technology of concentric triple tubes consisting from inside tube, Outside tube and Vacuum insulation tube. 3) Development of manufacturing technique of the moderator cell with complicated shapes. According to detail planed work procedures, replacement work was carried out. As results, the working days were reduced to 80% of old ones. The radiation dose was also reduced due to reduction of working days. It was verified by measurement of neutrons characteristics that the replaced moderator cell has the same performance as that of the old moderator cell. The domestic manufacturing of the moderator cell was succeeded. As results, the replacement cost was reduced by development of domestic production technology. (author)

Culture of human cells in experimental units for spaceflight impacts on their behavior.

Science.gov (United States)

Cazzaniga, Alessandra; Moscheni, Claudia; Maier, Jeanette Am; Castiglioni, Sara

2017-05-01

Because space missions produce pathophysiological alterations such as cardiovascular disorders and bone demineralization which are very common on Earth, biomedical research in space is a frontier that holds important promises not only to counterbalance space-associated disorders in astronauts but also to ameliorate the health of Earth-bound population. Experiments in space are complex to design. Cells must be cultured in closed cell culture systems (from now defined experimental units (EUs)), which are biocompatible, functional, safe to minimize any potential hazard to the crew, and with a high degree of automation. Therefore, to perform experiments in orbit, it is relevant to know how closely culture in the EUs reflects cellular behavior under normal growth conditions. We compared the performances in these units of three different human cell types, which were recently space flown, i.e. bone mesenchymal stem cells, micro- and macrovascular endothelial cells. Endothelial cells are only slightly and transiently affected by culture in the EUs, whereas these devices accelerate mesenchymal stem cell reprogramming toward osteogenic differentiation, in part by increasing the amounts of reactive oxygen species. We conclude that cell culture conditions in the EUs do not exactly mimic what happens in a culture dish and that more efforts are necessary to optimize these devices for biomedical experiments in space. Impact statement Cell cultures represent valuable preclinical models to decipher pathogenic circuitries. This is true also for biomedical research in space. A lot has been learnt about cell adaptation and reaction from the experiments performed on many different cell types flown to space. Obviously, cell culture in space has to meet specific requirements for the safety of the crew and to comply with the unique environmental challenges. For these reasons, specific devices for cell culture in space have been developed. It is important to clarify whether these

Targeting tumor-initiating cells: Eliminating anabolic cancer stem cells with inhibitors of protein synthesis or by mimicking caloric restriction

Science.gov (United States)

Lamb, Rebecca; Harrison, Hannah; Smith, Duncan L.; Townsend, Paul A.; Jackson, Thomas; Ozsvari, Bela; Martinez-Outschoorn, Ubaldo E.; Pestell, Richard G.; Howell, Anthony; Lisanti, Michael P.; Sotgia, Federica

2015-01-01

We have used an unbiased proteomic profiling strategy to identify new potential therapeutic targets in tumor-initiating cells (TICs), a.k.a., cancer stem cells (CSCs). Towards this end, the proteomes of mammospheres from two breast cancer cell lines were directly compared to attached monolayer cells. This allowed us to identify proteins that were highly over-expressed in CSCs and/or progenitor cells. We focused on ribosomal proteins and protein folding chaperones, since they were markedly over-expressed in mammospheres. Overall, we identified >80 molecules specifically associated with protein synthesis that were commonly upregulated in mammospheres. Most of these proteins were also transcriptionally upregulated in human breast cancer cells in vivo, providing evidence for their potential clinical relevance. As such, increased mRNA translation could provide a novel mechanism for enhancing the proliferative clonal expansion of TICs. The proteomic findings were functionally validated using known inhibitors of protein synthesis, via three independent approaches. For example, puromycin (which mimics the structure of tRNAs and competitively inhibits protein synthesis) preferentially targeted CSCs in both mammospheres and monolayer cultures, and was ~10-fold more potent for eradicating TICs, than “bulk” cancer cells. In addition, rapamycin, which inhibits mTOR and hence protein synthesis, was very effective at reducing mammosphere formation, at nanomolar concentrations. Finally, mammosphere formation was also markedly inhibited by methionine restriction, which mimics the positive effects of caloric restriction in cultured cells. Remarkably, mammosphere formation was >18-fold more sensitive to methionine restriction and replacement, as directly compared to monolayer cell proliferation. Methionine is absolutely required for protein synthesis, since every protein sequence starts with a methionine residue. Thus, the proliferation and survival of CSCs is very sensitive to

Interdependence of initial cell density, drug concentration and exposure time revealed by real-time impedance spectroscopic cytotoxicity assay

DEFF Research Database (Denmark)

Caviglia, Claudia; Zor, Kinga; Canepa, Silvia

2015-01-01

We investigated the combined effect of the initial cell density (12 500, 35 000, 75 000, and 100 000 cells cm−2) and concentration of the anti-cancer drug doxorubicin on HeLa cells by performing timedependent cytotoxicity assays using real-time electrochemical impedance spectroscopy. A correlation...... between the rate of cell death and the initial cell seeding density was found at 2.5 μM doxorubicin concentration, whereas this was not observed at 5 or 100 μM. By sensing the changes in the cell–substrate interaction using impedance spectroscopy under static conditions, the onset of cytotoxicity...... was observed 5 h earlier than when using a standard colorimetric end-point assay (MTS) which measures changes in the mitochondrial metabolism. Furthermore, with the MTS assay no cytotoxicity was observed after 15 h of incubation with 2.5 μM doxorubicin, whereas the impedance showed at this time point cell...

A Quest for Initiating Cells of Head and Neck Cancer and Their Treatment

International Nuclear Information System (INIS)

Chen, Chao; Köberle, Beate; Kaufmann, Andreas M.; Albers, Andreas E.

2010-01-01

The biology of head and neck squamous cell carcinomas (HNSCC) and other cancers have been related to cancer stem-like cells (CSC). Specific markers, which vary considerably depending on tumor type or tissue of origin, characterize CSC. CSC are cancer initiating, sustaining and mostly quiescent. Compared to bulk tumors, CSC are less sensitive to chemo- and radiotherapy and may have low immunogenicity. Therapeutic targeting of CSC may improve clinical outcome. HNSCC has two main etiologies: human papillomavirus, a virus infecting epithelial stem cells, and tobacco and alcohol abuse. Here, current knowledge of HNSCC-CSC biology is reviewed and parallels to CSC of other origin are drawn where necessary for a comprehensive picture

Cell-State Transitions Regulated by SLUG Are Critical for Tissue Regeneration and Tumor Initiation

Directory of Open Access Journals (Sweden)

Sarah Phillips

2014-05-01

Full Text Available Perturbations in stem cell activity and differentiation can lead to developmental defects and cancer. We use an approach involving a quantitative model of cell-state transitions in vitro to gain insights into how SLUG/SNAI2, a key developmental transcription factor, modulates mammary epithelial stem cell activity and differentiation in vivo. In the absence of SLUG, stem cells fail to transition into basal progenitor cells, while existing basal progenitor cells undergo luminal differentiation; together, these changes result in abnormal mammary architecture and defects in tissue function. Furthermore, we show that in the absence of SLUG, mammary stem cell activity necessary for tissue regeneration and cancer initiation is lost. Mechanistically, SLUG regulates differentiation and cellular plasticity by recruiting the chromatin modifier lysine-specific demethylase 1 (LSD1 to promoters of lineage-specific genes to repress transcription. Together, these results demonstrate that SLUG plays a dual role in repressing luminal epithelial differentiation while unlocking stem cell transitions necessary for tumorigenesis.

Magnetoresistance oscillations of two-dimensional electron systems in lateral superlattices with structured unit cells

Science.gov (United States)

Gerhardts, Rolf R.

2015-11-01

Model calculations for commensurability oscillations of the low-field magnetoresistance of two-dimensional electron systems (2DES) in lateral superlattices, consisting of unit cells with an internal structure, are compared with recent experiments. The relevant harmonics of the effective modulation potential depend not only on the geometrical structure of the modulated unit cell, but also strongly on the nature of the modulation. While higher harmonics of an electrostatically generated surface modulation are exponentially damped at the position of the 2DES about 90 nm below the surface, no such damping appears for strain-induced modulation generated, e.g., by the deposition of stripes of calixarene resist on the surface before cooling down the sample.

International Space Station Nickel-Hydrogen Battery Start-Up and Initial Performance

Science.gov (United States)

Cohen, Fred; Dalton, Penni J.

2001-01-01

International Space Station (ISS) Electric Power System (EPS) utilizes Nickel-Hydrogen (Ni-H2) batteries as part of its power system to store electrical energy. The batteries are charged during insolation and discharged during eclipse. The batteries are designed to operate at a 35% depth of discharge (DOD) maximum during normal operation. Thirty eight individual pressure vessel (IPV) Ni-H2 battery cells are series-connected and packaged in an Orbital Replacement Unit (ORU). Two ORUs are series-connected utilizing a total of 76 cells, to form one battery. The ISS is the first application for low earth orbit (LEO) cycling of this quantity of series-connected cells. The P6 Integrated Equipment Assembly (IEA) containing the initial ISS high-power components was successfully launched on November 30, 2000. The IEA contains 12 Battery Subassembly ORUs (6 batteries) that provide station power during eclipse periods. This paper will describe the battery hardware configuration, operation, and role in providing power to the main power system of the ISS. We will also discuss initial battery start-up and performance data.

Influence of the initial conditions for the numerical simulation of two-phase slug flow

Energy Technology Data Exchange (ETDEWEB)

Pachas Napa, Alex A.; Morales, Rigoberto E.M.; Medina, Cesar D. Perea

2010-07-01

Multiphase flows in pipelines commonly show several patterns depending on the flow rate, geometry and physical properties of the phases. In oil production, the slug flow pattern is the most common among the others. This flow pattern is characterized by an intermittent succession in space and time of an aerated liquid slug and an elongated gas bubble with a liquid film. Slug flow is studied through the slug tracking model described as one-dimensional and Lagrangian frame referenced. In the model, the mass and the momentum balance equations are applied in control volumes constituted by the gas bubble and the liquid slug. Initial conditions must be determined, which need to reproduce the intermittence of the flow pattern. These initial conditions are given by a sequence of flow properties for each unit cell. Properties of the unit cell in initial conditions should reflect the intermittence, for which they can be analyzed in statistical terms. Therefore, statistical distributions should be obtained for the slug flow variables. Distributions are complemented with the mass balance and the bubble design model. The objective of the present work is to obtain initial conditions for the slug tracking model that reproduce a better adjustment of the fluctuating properties for different pipe inclinations (horizontal, vertical or inclined). The numerical results are compared with experimental data obtained by PFG/FEM/UNICAMP for air-water flow at 0 deg, 45 deg and 90 deg and good agreement is observed. (author)

Regulatory T cells predict the time to initial treatment in early stage chronic lymphocytic leukemia.

Science.gov (United States)

Weiss, Lukas; Melchardt, Thomas; Egle, Alexander; Grabmer, Christoph; Greil, Richard; Tinhofer, Inge

2011-05-15

Early stage chronic lymphocytic leukemia is characterized by a highly variable course of disease. Because it is believed that regulatory T cells (T(regs) ) are potent suppressors of antitumor immunity, the authors hypothesized that increased T(regs) may favor disease progression. T(reg) levels (cluster of differentiation 3 [CD3]-positive, [CD4]-positive, CD25-positive, and CD127-negative) in peripheral blood from 102 patients were analyzed by flow cytometry. Statistical analysis was used to evaluate correlations with clinical data. The relative T(reg) numbers in CD4-positive T cells were significantly greater in patients with chronic lymphocytic leukemia compared with the numbers in a control group of 170 healthy individuals (P = .001). Patients were divided into 2 groups using a median T(reg) value of 9.7% (the percentage of CD4-positive T cells). Patients with higher T(reg) levels had a significantly shorter time to initial treatment (median, 5.9 years) compared with patients who had lower T(reg) levels (median, 11.7 years; log-rank P = .019). Furthermore, T(reg) levels (the percentage of CD4-positive T cells) had significant prognostic power to predict the time to initial treatment in univariate analysis (P = .023) and in multivariate Cox regression analysis that included the variables Rai stage, immunoglobulin heavy-chain variable region gene mutational status, chromosomal aberrations, and CD38 expression (P = .028). Higher T(reg) levels had significant and independent prognostic power for predicting the time to initial treatment in patients with low to intermediate stage chronic lymphocytic leukemia. 2010 American Cancer Society.

Divergent regeneration-competent cells adopt a common mechanism for callus initiation in angiosperms.

Science.gov (United States)

Hu, Bo; Zhang, Guifang; Liu, Wu; Shi, Jianmin; Wang, Hua; Qi, Meifang; Li, Jiqin; Qin, Peng; Ruan, Ying; Huang, Hai; Zhang, Yijing; Xu, Lin

2017-06-01

In tissue culture, the formation of callus from detached explants is a key step in plant regeneration; however, the regenerative abilities in different species are variable. While nearly all parts of organs of the dicot Arabidopsis thaliana are ready for callus formation, mature regions of organs in monocot rice ( Oryza sativa ) and other cereals are extremely unresponsive to tissue culture. Whether there is a common molecular mechanism beyond these different regenerative phenomena is unclear. Here we show that the Arabidopsis and rice use different regeneration-competent cells to initiate callus, whereas the cells all adopt WUSCHEL-RELATED HOMEOBOX 11 ( WOX11 ) and WOX5 during cell fate transition. Different from Arabidopsis which maintains regeneration-competent cells in mature organs, rice exhausts those cells during organ maturation, resulting in regenerative inability in mature organs. Our study not only explains this old perplexity in agricultural biotechnology, but also provides common molecular markers for tissue culture of different angiosperm species.

Evaluating U.S. States climate change initiatives

International Nuclear Information System (INIS)

Silva, P.

2004-01-01

This paper evaluates sub-federal efforts to mitigate climate change in the United States through a range of climate-relevant initiatives, identifying principal trends and detailing climate-relevant initiatives in several states. These strategies include renewable electricity mandates, State and regional greenhouse gas emissions inventories, mandatory greenhouse gas emissions reporting, State greenhouse gas emissions caps, greenhouse gas emissions reductions from motor vehicles, and greenhouse gas emissions cap-and-trade programs for electric generation in several States. Many municipalities in the United States are also pursuing a range of climate-relevant initiatives, those actions are beyond the scope of this paper, but it should be noted they also influence state and national consideration of climate-relevant initiatives in the United States. (author)

Evaluating U.S. States climate change initiatives

Energy Technology Data Exchange (ETDEWEB)

Silva, P

2004-07-01

This paper evaluates sub-federal efforts to mitigate climate change in the United States through a range of climate-relevant initiatives, identifying principal trends and detailing climate-relevant initiatives in several states. These strategies include renewable electricity mandates, State and regional greenhouse gas emissions inventories, mandatory greenhouse gas emissions reporting, State greenhouse gas emissions caps, greenhouse gas emissions reductions from motor vehicles, and greenhouse gas emissions cap-and-trade programs for electric generation in several States. Many municipalities in the United States are also pursuing a range of climate-relevant initiatives, those actions are beyond the scope of this paper, but it should be noted they also influence state and national consideration of climate-relevant initiatives in the United States. (author)

Political initiative needed in the United States

International Nuclear Information System (INIS)

Hollister, K.

1979-01-01

The financing of nuclear power stations in the United States is in trouble mainly because of the long lead times caused by licensing. It will again become feasible when legislation reduces the construction time to eight years or less. The overriding need to protect the dollar by reducing oil imports, will lead the US Government to embrace nuclear power openly. (U.K.)

Drug-resistant colon cancer cells produce high carcinoembryonic antigen and might not be cancer-initiating cells

Directory of Open Access Journals (Sweden)

Lee HC

2013-06-01

Full Text Available Hsin-chung Lee,1,2 Qing-Dong Ling,1,3 Wan-Chun Yu,4 Chunh-Ming Hung,4 Ta-Chun Kao,4 Yi-Wei Huang,4 Akon Higuchi3–51Graduate Institute of Systems Biology and Bioinformatics, National Central University, Jhongli, Taoyuan, 2Department of Surgery, Cathay General Hospital, Da'an District, Taipei, 3Cathay Medical Research Institute, Cathay General Hospital, Hsi-Chi City, Taipei, 4Department of Chemical and Materials Engineering, National Central University, Jhongli, Taoyuan, Taiwan; 5Department of Reproduction, National Research Institute for Child Health and Development, Okura, Tokyo, JapanPurpose: We evaluated the higher levels of carcinoembryonic antigen (CEA secreted by the LoVo human colon carcinoma cells in a medium containing anticancer drugs. Drug-resistant LoVo cells were analyzed by subcutaneously xenotransplanting them into mice. The aim of this study was to evaluate whether the drug-resistant cells isolated in this study were cancer-initiating cells, known also as cancer stem cells (CSCs.Methods: The production of CEA was investigated in LoVo cells that were cultured with 0–10 mM of anticancer drugs, and we evaluated the increase in CEA production by the LoVo cells that were stimulated by anticancer drug treatment. The expression of several CSC markers in LoVo cells treated with anticancer drugs was also evaluated. Following anticancer drug treatment, LoVo cells were injected subcutaneously into the flanks of severe combined immunodeficiency mice in order to evaluate the CSC fraction.Results: Production of CEA by LoVo cells was stimulated by the addition of anticancer drugs. Drug-resistant LoVo cells expressed lower levels of CSC markers, and LoVo cells treated with any of the anticancer drugs tested did not generate tumors within 8 weeks from when the cells were injected subcutaneously into severe combined immunodeficiency mice. These results suggest that the drug-resistant LoVo cells have a smaller population of CSCs than the

Effect of intravenous administration of D-lysergic acid diethylamide on initiation of protein synthesis in a cell-free system derived from brain.

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Cosgrove, J W; Brown, I R

1984-05-01

An initiating cell-free protein synthesis system derived from brain was utilized to demonstrate that the intravenous injection of D-lysergic acid diethylamide (LSD) to rabbits resulted in a lesion at the initiation stage of brain protein synthesis. Three inhibitors of initiation, edeine, poly(I), and aurintricarboxylic acid were used to demonstrate a reduction in initiation-dependent amino acid incorporation in the brain cell-free system. One hour after LSD injection, there was also a measurable decrease in the formation of 40S and 80S initiation complexes in vitro, using either [35S]methionine or [35S]Met-tRNAf. Analysis of the methionine pool size after LSD administration indicated there was no change in methionine levels. Analysis of the formation of initiation complexes in the brain cell-free protein synthesis system prepared 6 h after LSD administration indicated that there was a return to control levels at this time. The effects of LSD on steps in the initiation process are thus reversible.

A simplistic analytical unit cell based model for the effective thermal conductivity of high porosity open-cell metal foams

International Nuclear Information System (INIS)

Yang, X H; Kuang, J J; Lu, T J; Han, F S; Kim, T

2013-01-01

We present a simplistic yet accurate analytical model for the effective thermal conductivity of high porosity open-cell metal foams saturated in a low conducting fluid (air). The model is derived analytically based on a realistic representative unit cell (a tetrakaidecahedron) under the assumption of one-dimensional heat conduction along highly tortuous-conducting ligaments at high porosity ranges (ε ⩾ 0.9). Good agreement with existing experimental data suggests that heat conduction along highly conducting and tortuous ligaments predominantly defines the effective thermal conductivity of open-cell metal foams with negligible conduction in parallel through the fluid phase. (paper)

Three-dimensional reconstruction of statistically optimal unit cells of polydisperse particulate composites from microtomography

International Nuclear Information System (INIS)

Lee, H.; Brandyberry, M.; Tudor, A.; Matous, K.

2009-01-01

In this paper, we present a systematic approach for characterization and reconstruction of statistically optimal representative unit cells of polydisperse particulate composites. Microtomography is used to gather rich three-dimensional data of a packed glass bead system. First-, second-, and third-order probability functions are used to characterize the morphology of the material, and the parallel augmented simulated annealing algorithm is employed for reconstruction of the statistically equivalent medium. Both the fully resolved probability spectrum and the geometrically exact particle shapes are considered in this study, rendering the optimization problem multidimensional with a highly complex objective function. A ten-phase particulate composite composed of packed glass beads in a cylindrical specimen is investigated, and a unit cell is reconstructed on massively parallel computers. Further, rigorous error analysis of the statistical descriptors (probability functions) is presented and a detailed comparison between statistics of the voxel-derived pack and the representative cell is made.

Conjunctival mass as an initial presentation of mantle cell lymphoma: a case report

Directory of Open Access Journals (Sweden)

Khanlari Mahsa

2012-12-01

Full Text Available Abstract Background To describe a rare manifestation of mantle cell lymphoma (MCL in conjunctiva, with clinical, hisologic, immunohistologic and genetic findings together with review of the Literature. Case presentation Most ocular adnexal lymphomas are extranodal marginal zone B-cell lymphomas of mucosa-associated lymphoid tissue (MALT. A few cases of ocular adnexal mantle cell lymphomas have been reported in the literature. We present a case of mantle cell lymphoma presenting as right conjunctival mass of at least three months duration in a 64-year-old man. Histopathologic examination showed a proliferation of monomorphous small-to-medium-sized lymphoid cells with cleaved nuclei in the subconjunctiva. By immunohistochemistry, the infiltrate was positive for CD20, CD5, BCL-2, cyclin D1, and the transcription factor SOX11. Fluorescent in situ hybridization demonstrated the presence of IGH-CCND1 fusion indicating t(11;14. Conclusion A rigorous approach to initial diagnosis and staging of small cell lymphomas of the ocular adnexa is needed. The recognition of ocular MCL requires appropriate immunohistochemical staining and/or genetic confirmation to differentiate this rare form of presentation of MCL from other more frequent small cell lymphomas.

Fluorescent lamp recycling initiatives in the United States and a recycling proposal based on extended producer responsibility and product stewardship concepts.

Science.gov (United States)

Silveira, Geraldo Tr; Chang, Shoou-Yuh

2011-06-01

This paper presents an overview of mercury-containing lamp (MCL) recycling initiatives currently available in the world, especially in the United States. The majority of MCLs contain mercury which is a neurotoxin, a persistent pollutant in the environment, and can bioaccumulate in the food chain. Although there are some recycling options in the United States, collection rates are still at 23% of all potential used MCLs. This shows that citizens are either indifferent to or unaware of the recycling alternatives. On the other hand, MCL recycling seems not to be a cost-effective process and, for this reason, in the United States, take-back programmes are still sponsored only by consumers or municipalities. A few retailers have recently initiated limited take-back alternatives and manufacturers have not yet supported financially any consistent recycling alternative in the country. Considering successful experiences, this paper makes a suggestion for an MCL recycling system based on the concepts of extended producer responsibility and product stewardship. A manufacturer-importer advance recycling fee is proposed to finance the collection and recycling system while a MCL-energy recycling fee supported by the energy sector creates a lamp refund process. 'PRO Lamp', a producer responsibility organization, will manage the entire system through a widespread public-private agreement.

Genetic subclone architecture of tumor clone-initiating cells in colorectal cancer.

Science.gov (United States)

Giessler, Klara M; Kleinheinz, Kortine; Huebschmann, Daniel; Balasubramanian, Gnana Prakash; Dubash, Taronish D; Dieter, Sebastian M; Siegl, Christine; Herbst, Friederike; Weber, Sarah; Hoffmann, Christopher M; Fronza, Raffaele; Buchhalter, Ivo; Paramasivam, Nagarajan; Eils, Roland; Schmidt, Manfred; von Kalle, Christof; Schneider, Martin; Ulrich, Alexis; Scholl, Claudia; Fröhling, Stefan; Weichert, Wilko; Brors, Benedikt; Schlesner, Matthias; Ball, Claudia R; Glimm, Hanno

2017-07-03

A hierarchically organized cell compartment drives colorectal cancer (CRC) progression. Genetic barcoding allows monitoring of the clonal output of tumorigenic cells without prospective isolation. In this study, we asked whether tumor clone-initiating cells (TcICs) were genetically heterogeneous and whether differences in self-renewal and activation reflected differential kinetics among individual subclones or functional hierarchies within subclones. Monitoring genomic subclone kinetics in three patient tumors and corresponding serial xenografts and spheroids by high-coverage whole-genome sequencing, clustering of genetic aberrations, subclone combinatorics, and mutational signature analysis revealed at least two to four genetic subclones per sample. Long-term growth in serial xenografts and spheroids was driven by multiple genomic subclones with profoundly differing growth dynamics and hence different quantitative contributions over time. Strikingly, genetic barcoding demonstrated stable functional heterogeneity of CRC TcICs during serial xenografting despite near-complete changes in genomic subclone contribution. This demonstrates that functional heterogeneity is, at least frequently, present within genomic subclones and independent of mutational subclone differences. © 2017 Giessler et al.

An investigation of the initial attachment and orientation of osteoblast-like cells on laser grooved Ti-6Al-4V surfaces

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Chen, J., E-mail: jianboc@Princeton.EDU [Princeton Institute of Science and Technology of Materials, Princeton University, Princeton, NJ 08544 (United States); Department of Mechanical and Aerospace Engineering, Princeton University, Princeton, NJ 08544 (United States); Ulerich, J.P. [Department of Mechanical and Aerospace Engineering, Princeton University, Princeton, NJ 08544 (United States); Abelev, E. [Department of Chemistry, Princeton University, Princeton, NJ 08544 (United States); Fasasi, A. [Princeton Institute of Science and Technology of Materials, Princeton University, Princeton, NJ 08544 (United States); Center for Energy Research, Obafemi Awolowo University, Ile-Ife (Nigeria); Arnold, C.B.; Soboyejo, W.O. [Princeton Institute of Science and Technology of Materials, Princeton University, Princeton, NJ 08544 (United States); Department of Mechanical and Aerospace Engineering, Princeton University, Princeton, NJ 08544 (United States)

2009-05-05

This paper presents the results of an experimental study of the initial cell spreading and adhesion on longitudinally- and transversally-oriented micro-grooves produced by the laser irradiation of laser grooved Ti-6Al-4V surfaces. The initial spreading and orientations of human osteosarcoma (HOS) cells were observed and quantified after 15-min, 1-hour, 4-hour and 24-hour cell culture periods. Immuno-fluorescence staining of adhesion proteins (actin and vinculin) was then used to study the spreading and adhesion of HOS cells in 1 hour and 4 hour culture experiments. The initial cell adhesion was also quantified using enzymatic detachment tests. The results showed that cell spreading and adhesion were enhanced by longitudinally- and transversally-oriented micro-grooves. The effects, which increase with time, were not remarkable after 1 hour, but obvious after 4 hours. Contact guidance was found to promote cell adhesion due to the increase in interactions between the focal adhesions and the patterned extra-cellular matrix (ECM) proteins on the laser micro-grooved surfaces.

An investigation of the initial attachment and orientation of osteoblast-like cells on laser grooved Ti-6Al-4V surfaces

International Nuclear Information System (INIS)

Chen, J.; Ulerich, J.P.; Abelev, E.; Fasasi, A.; Arnold, C.B.; Soboyejo, W.O.

2009-01-01

This paper presents the results of an experimental study of the initial cell spreading and adhesion on longitudinally- and transversally-oriented micro-grooves produced by the laser irradiation of laser grooved Ti-6Al-4V surfaces. The initial spreading and orientations of human osteosarcoma (HOS) cells were observed and quantified after 15-min, 1-hour, 4-hour and 24-hour cell culture periods. Immuno-fluorescence staining of adhesion proteins (actin and vinculin) was then used to study the spreading and adhesion of HOS cells in 1 hour and 4 hour culture experiments. The initial cell adhesion was also quantified using enzymatic detachment tests. The results showed that cell spreading and adhesion were enhanced by longitudinally- and transversally-oriented micro-grooves. The effects, which increase with time, were not remarkable after 1 hour, but obvious after 4 hours. Contact guidance was found to promote cell adhesion due to the increase in interactions between the focal adhesions and the patterned extra-cellular matrix (ECM) proteins on the laser micro-grooved surfaces.

Initial Assessment of Parallelization of Monte Carlo Calculation using Graphics Processing Units

International Nuclear Information System (INIS)

Choi, Sung Hoon; Joo, Han Gyu

2009-01-01

Monte Carlo (MC) simulation is an effective tool for calculating neutron transports in complex geometry. However, because Monte Carlo simulates each neutron behavior one by one, it takes a very long computing time if enough neutrons are used for high precision of calculation. Accordingly, methods that reduce the computing time are required. In a Monte Carlo code, parallel calculation is well-suited since it simulates the behavior of each neutron independently and thus parallel computation is natural. The parallelization of the Monte Carlo codes, however, was done using multi CPUs. By the global demand for high quality 3D graphics, the Graphics Processing Unit (GPU) has developed into a highly parallel, multi-core processor. This parallel processing capability of GPUs can be available to engineering computing once a suitable interface is provided. Recently, NVIDIA introduced CUDATM, a general purpose parallel computing architecture. CUDA is a software environment that allows developers to manage GPU using C/C++ or other languages. In this work, a GPU-based Monte Carlo is developed and the initial assessment of it parallel performance is investigated

Action potentials in retinal ganglion cells are initiated at the site of maximal curvature of the extracellular potential.

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Eickenscheidt, Max; Zeck, Günther

2014-06-01

The initiation of an action potential by extracellular stimulation occurs after local depolarization of the neuronal membrane above threshold. Although the technique shows remarkable clinical success, the site of action and the relevant stimulation parameters are not completely understood. Here we identify the site of action potential initiation in rabbit retinal ganglion cells (RGCs) interfaced to an array of extracellular capacitive stimulation electrodes. We determine which feature of the extracellular potential governs action potential initiation by simultaneous stimulation and recording RGCs interfaced in epiretinal configuration. Stimulation electrodes were combined to areas of different size and were presented at different positions with respect to the RGC. Based on stimulation by electrodes beneath the RGC soma and simultaneous sub-millisecond latency measurement we infer axonal initiation at the site of maximal curvature of the extracellular potential. Stimulation by electrodes at different positions along the axon reveals a nearly constant threshold current density except for a narrow region close to the cell soma. These findings are explained by the concept of the activating function modified to consider a region of lower excitability close to the cell soma. We present a framework how to estimate the site of action potential initiation and the stimulus required to cross threshold in neurons tightly interfaced to capacitive stimulation electrodes. Our results underscore the necessity of rigorous electrical characterization of the stimulation electrodes and of the interfaced neural tissue.

Study of accelerated unit unloading mode initiated by turbine feed pump trip with TVSA fuel assemblies operation in WWER-1000

International Nuclear Information System (INIS)

Borysenko, V.I.; Kadenko, I.N.; Samoilenko, D.V.

2012-01-01

This paper provides the study results of accelerated unit unloading mode (AUU) initiated at WWER-1000 unit operated at 100 % power and its expediency in the event of single Turbo Feed Pump (TFP) failure. Modeling was performed using an advanced calculation code RELAP/SCDAPSIM/Mod3.4 and relevant model for KhNPP Unit No. 2. As the study shows, SCRAM cannot be prevented in case of failure of 3 main circulation pumps due to steam generators (SG) level drop. Based on the results obtained, it is reasonably justified to allow SCRAM signal instead of AUU activation in case of single TFP failure at power level more than 90 % of N n om. This will provide more sparing temperature modes for fuel assemblies and equipment, as well as prevent additional thermal cycling loads and violation of safe operation limits as SG water levels

Biological insights into the expression of translation initiation factors from recombinant CHOK1SV cell lines and their relationship to enhanced productivity.

Science.gov (United States)

Mead, Emma J; Masterton, Rosalyn J; Feary, Marc; Obrezanova, Olga; Zhang, Lin; Young, Robert; Smales, C Mark

2015-12-15

Translation initiation is on the critical pathway for the production of monoclonal antibodies (mAbs) by mammalian cells. Formation of a closed loop structure comprised of mRNA, a number of eukaryotic initiation factors (eIFs) and ribosomal proteins has been proposed to aid re-initiation of translation and therefore increase global translational efficiency. We have determined mRNA and protein levels of the key components of the closed loop, eIFs (eIF3a, eIF3b, eIF3c, eIF3h, eIF3i and eIF4G1), poly(A)-binding protein (PABP) 1 and PABP-interacting protein 1 (PAIP1), across a panel of 30 recombinant mAb-producing GS-CHOK1SV cell lines with a broad range of growth characteristics and production levels of a model recombinant mAb. We have used a multi-level statistical approach to investigate the relationship between key performance indicators (cell growth and recombinant antibody productivity) and the intracellular amounts of target translation initiation factor proteins and the mRNAs encoding them. We show that high-producing cell lines maintain amounts of the translation initiation factors involved in the formation of the closed loop mRNA, maintaining these proteins at appropriate levels to deliver enhanced recombinant protein production. We then utilize knowledge of the amounts of these factors to build predictive models for and use cluster analysis to identify, high-producing cell lines. The present study therefore defines the translation initiation factor amounts that are associated with highly productive recombinant GS-CHOK1SV cell lines that may be targets for screening highly productive cell lines or to engineer new host cell lines with the potential for enhanced recombinant antibody productivity. © 2015 Authors; published by Portland Press Limited.

Indoleamine-2,3-dioxygenase elevated in tumor-initiating cells is suppressed by mitocans

Czech Academy of Sciences Publication Activity Database

Stapelberg, M.; Zobalová, Renata; Nguyen, M.N.; Walker, T.; Stantic, M.; Goodwin, J.; Pasdar, E.A.; Thai, T.; Prokopová, Kateřina; Yan, B.; Hall, S.; de Pennington, N.; Thomas, S.R.; Grant, G.; Štursa, Jan; Bajziková, Martina; Meedeniya, A.C.B.; Truksa, Jaroslav; Ralph, S. J.; Ansorge, O.; Dong, L.-F.; Neužil, Jiří

2014-01-01

Roč. 67, FEB (2014), s. 41-50 ISSN 0891-5849 R&D Projects: GA ČR(CZ) GAP301/10/1937; GA ČR GAP305/12/1708 Institutional support: RVO:86652036 ; RVO:61388963 Keywords : IDO * Tumor-initiating cells * Mitocans * Mitochondrially targeted vitamin E succinate Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.736, year: 2014

Timing of initiation of macronuclear DNA synthesis is set during the preceding cell cycle in Paramecium tetraurelia: analysis of the effects of abrupt changes in nutrient level

International Nuclear Information System (INIS)

Ching, A.S.L.; Berger, J.D.

1986-01-01

In many eukaryotic organisms, initiation of DNA synthesis is associated with a major control point within the cell cycle and reflects the commitment of the cell to the DNA replication-division portion of the cell cycle. In paramecium, the timing of DNA synthesis initiation is established prior to fission during the preceding cell cycle. DNA synthesis normally starts at 0.25 in the cell cycle. When dividing cells are subjected to abrupt nutrient shift-up by transfer from a chemostat culture to medium with excess food, or shift-down from a well-fed culture to exhausted medium, DNA synthesis initiation in the post-shift cell cycle occurs at 0.25 of the parental cell cycle and not at either 0.25 in the post-shift cell cycle or at 0.25 in the equilibrium cell cycle produced under the post-shift conditions. The long delay prior to initiation of DNA synthesis following nutritional shift-up is not a consequence of continued slow growth because the rate of protein synthesis increases rapidly to the normal level after shift-up. Analysis of the relation between increase in cell mass and initiation of DNA synthesis following nutritional shifts indicates that increase in cell mass, per se, is neither a necessary nor a sufficient condition for initiation of DNA synthesis, in spite of the strong association between accumulation of cell mass and initiation of DNA synthesis in cells growing under steady-state conditions

Histone deacetylase inhibitors reduce the number of herpes simplex virus-1 genomes initiating expression in individual cells

Directory of Open Access Journals (Sweden)

Lev Shapira

2016-12-01

Full Text Available Although many viral particles can enter a single cell, the number of viral genomes per cell that establish infection is limited. However, mechanisms underlying this restriction were not explored in depth. For herpesviruses, one of the possible mechanisms suggested is chromatinization and silencing of the incoming genomes. To test this hypothesis, we followed infection with three herpes simplex virus 1 (HSV-1 fluorescence-expressing recombinants in the presence or absence of histone deacetylases inhibitors (HDACi’s. Unexpectedly, a lower number of viral genomes initiated expression in the presence of these inhibitors. This phenomenon was observed using several HDACi: Trichostatin A (TSA, Suberohydroxamic Acid (SBX, Valporic Acid (VPA and Suberoylanilide Hydoxamic Acid (SAHA. We found that HDACi presence did not change the progeny outcome from the infected cells but did alter the kinetic of the gene expression from the viral genomes. Different cell types (HFF, Vero and U2OS, which vary in their capability to activate intrinsic and innate immunity, show a cell specific basal average number of viral genomes establishing infection. Importantly, in all cell types, treatment with TSA reduced the number of viral genomes. ND10 nuclear bodies are known to interact with the incoming herpes genomes and repress viral replication. The viral immediate early protein, ICP0, is known to disassemble the ND10 bodies and to induce degradation of some of the host proteins in these domains. HDACi treated cells expressed higher levels of some of the host ND10 proteins (PML and ATRX, which may explain the lower number of viral genomes initiating expression per cell. Corroborating this hypothesis, infection with three HSV-1 recombinants carrying a deletion in the gene coding for ICP0, show a reduction in the number of genomes being expressed in U2OS cells. We suggest that alterations in the levels of host proteins involved in intrinsic antiviral defense may result in

Local government units initiatives on coastal resource management in adjacent municipalities in Camarines Sur, Philippines

Science.gov (United States)

Faustino, A. Z.; Madela, H. L.

2018-03-01

This research was conducted to determine the local government units (LGUs) initiatives on coastal resource management (CRM) in adjacent municipalities in Camarines Sur, Philippines. The respondents of this study are 100 fisherfolk leaders in the municipalities of Calabanga, Tinambac and Siruma. Descriptive, comparative and evaluative methods of research were employed and a survey questionnaire was used as the primary tool in data gathering. On the test of difference, the computed F-value of 12.038 and p-value of .001 revealed a very high difference in the implementation of CRM initiatives in the adjacent municipalities. The respondents in this study live below the poverty threshold. The intrusion of commercial fishers and the use of active fishing gears inside the 15-km municipal waters significantly affect the marine habitat while fishpond conversion kills the natural cycle in the mangrove forests. However, the FOs membership in the Municipal Fisheries and Aquatic Resources Management Council empower them to engage in governance which can be a venue for them to recommend policies related to CRM. As a result of this study, a CRM monitoring and evaluation model was crafted to guide the LGUs in the review, revision and crafting of CRM programs.

BMI-1 targeting interferes with patient-derived tumor-initiating cell survival and tumor growth in prostate cancer

Science.gov (United States)

Yusuff, Shamila; Davis, Stephani; Flaherty, Kathleen; Huselid, Eric; Patrizii, Michele; Jones, Daniel; Cao, Liangxian; Sydorenko, Nadiya; Moon, Young-Choon; Zhong, Hua; Medina, Daniel J.; Kerrigan, John; Stein, Mark N.; Kim, Isaac Y.; Davis, Thomas W.; DiPaola, Robert S.; Bertino, Joseph R.; Sabaawy, Hatem E.

2016-01-01

Purpose Current prostate cancer (PCa) management calls for identifying novel and more effective therapies. Self-renewing tumor-initiating cells (TICs) hold intrinsic therapy-resistance and account for tumor relapse and progression. As BMI-1 regulates stem cell self-renewal, impairing BMI-1 function for TICs-tailored therapies appears to be a promising approach. Experimental design We have previously developed a combined immunophenotypic and time-of-adherence assay to identify CD49bhiCD29hiCD44hi cells as human prostate TICs. We utilized this assay with patient derived prostate cancer cells and xenograft models to characterize the effects of pharmacological inhibitors of BMI-1. Results We demonstrate that in cell lines and patient-derived TICs, BMI-1 expression is upregulated and associated with stem cell-like traits. From a screened library, we identified a number of post-transcriptional small molecules that target BMI-1 in prostate TICs. Pharmacological inhibition of BMI-1 in patient-derived cells significantly decreased colony formation in vitro and attenuated tumor initiation in vivo, thereby functionally diminishing the frequency of TICs, particularly in cells resistant to proliferation- and androgen receptor (AR)-directed therapies, without toxic effects on normal tissues. Conclusions Our data offer a paradigm for targeting TICs and support the development of BMI-1-targeting therapy for a more effective PCa treatment. PMID:27307599

Initial slope of human tumor cell survival curves: its modification by the oxic cell sensitizer beta-arabinofuranosyladenine

International Nuclear Information System (INIS)

Chavaudra, N.; Halimi, M.; Parmentier, C.; Gaillard, N.; Grinfeld, S.; Malaise, E.P.

1989-01-01

The initial slope of the survival curve, which is a characteristic of each tumor cell line, varies with the histological group of the tumor. It is one of the factors on which clinical radioresponsiveness depends. The DNA dependant DNA polymerase inhibitor beta-ara A acts as an oxic cell sensitizer. This study was carried out on human tumor cell lines to look for a correlation between the degree of radiosensitization induced by beta-ara A and the radiosensitivity of a given cell line. Six human tumor cell lines with different radiosensitivities were used (the survival rate at 2 Gy and D ranged from 20 to 73% and from 1.2 to 3.2 Gy, respectively). beta-ara A had a major toxic effect on all cell lines but this varied greatly from one cell line to another and was concentration dependant; this toxic effect was taken into account when calculating the surviving fractions. For all cell lines, beta-ara A acted as an oxic radiosensitizer and the radiosensitization was concentration dependant. Analysis of the survival curves of the 6 cell lines using the linear quadratic model showed that concentrations of beta-ara A between 200 and 1000 microM induced an increase in the linear component while the quadratic component underwent no systematic change. The sensitizing enhancement ratio (SER) measured from the Ds ratios, varied greatly from one line to another. For example, at a concentration of 500 microM, the extreme values of Ds ratios were 1.5 and 2.6. The radiosensitization is greater, the higher the radiosensitivity of the cell line studied during exponential growth. The results do not favor the use of beta-ara A in the treatment of intrinsically radioresistant human tumors

Initial slope of human tumor cell survival curves: its modification by the oxic cell sensitizer beta-arabinofuranosyladenine

Energy Technology Data Exchange (ETDEWEB)

Chavaudra, N.; Halimi, M.; Parmentier, C.; Gaillard, N.; Grinfeld, S.; Malaise, E.P.

1989-05-01

The initial slope of the survival curve, which is a characteristic of each tumor cell line, varies with the histological group of the tumor. It is one of the factors on which clinical radioresponsiveness depends. The DNA dependant DNA polymerase inhibitor beta-ara A acts as an oxic cell sensitizer. This study was carried out on human tumor cell lines to look for a correlation between the degree of radiosensitization induced by beta-ara A and the radiosensitivity of a given cell line. Six human tumor cell lines with different radiosensitivities were used (the survival rate at 2 Gy and D ranged from 20 to 73% and from 1.2 to 3.2 Gy, respectively). beta-ara A had a major toxic effect on all cell lines but this varied greatly from one cell line to another and was concentration dependant; this toxic effect was taken into account when calculating the surviving fractions. For all cell lines, beta-ara A acted as an oxic radiosensitizer and the radiosensitization was concentration dependant. Analysis of the survival curves of the 6 cell lines using the linear quadratic model showed that concentrations of beta-ara A between 200 and 1000 microM induced an increase in the linear component while the quadratic component underwent no systematic change. The sensitizing enhancement ratio (SER) measured from the Ds ratios, varied greatly from one line to another. For example, at a concentration of 500 microM, the extreme values of Ds ratios were 1.5 and 2.6. The radiosensitization is greater, the higher the radiosensitivity of the cell line studied during exponential growth. The results do not favor the use of beta-ara A in the treatment of intrinsically radioresistant human tumors.

Experimental broadband absorption enhancement in silicon nanohole structures with optimized complex unit cells.

Science.gov (United States)

Lin, Chenxi; Martínez, Luis Javier; Povinelli, Michelle L

2013-09-09

We design silicon membranes with nanohole structures with optimized complex unit cells that maximize broadband absorption. We fabricate the optimized design and measure the optical absorption. We demonstrate an experimental broadband absorption about 3.5 times higher than an equally-thick thin film.

Program-level and contextual-level determinants of low-median CD4+ cell count in cohorts of persons initiating ART in eight sub-Saharan African countries.

Science.gov (United States)

Nash, Denis; Wu, Yingfeng; Elul, Batya; Hoos, David; El Sadr, Wafaa

2011-07-31

In sub-Saharan Africa, many patients initiate antiretroviral therapy (ART) at CD4 cell counts much lower than those recommended in national guidelines. We examined program-level and contextual-level factors associated with low median CD4 cell count at ART initiation in populations initiating ART. Multilevel analysis of aggregate and program-level service delivery data. We examined data on 1690 cohorts of patients initiating ART during 2004-2008 in eight sub-Saharan African countries. Cohorts with median CD4 less than 111 cells/μl (the lowest quartile) were classified as having low median CD4 cell count at ART initiation. Cohort information was combined with time-updated program-level data and subnational contextual-level data, and analyzed using multilevel models. The 1690 cohorts had median CD4 cell count of 136 cells/μl and included 121,504 patients initiating ART at 267 clinics. Program-level factors associated with low cohort median CD4 cell count included urban setting [adjusted odds ratio (AOR) 2.1; 95% confidence interval (CI) 1.3-3.3], lower provider-to-patient ratio (AOR 2.2; 95% CI 1.3-4.0), no PMTCT program (AOR 3.6; 95% CI 1.0-12.8), outreach services for ART patients only vs. both pre-ART and ART patients (AOR 2.4; 95% CI 1.5-3.9), fewer vs. more adherence support services (AOR 1.6; 95% CI 1.0-2.5), and smaller cohort size (AOR 2.5; 95% CI 1.4-4.5). Contextual-level factors associated with low cohort median CD4 cell count included initiating ART in areas where a lower proportion of the population heard of AIDS, tested for HIV recently, and a higher proportion believed 'limiting themselves to one HIV-uninfected sexual partner reduces HIV risk'. Determinants of CD4 cell count at ART initiation in populations initiating ART operate at multiple levels. Structural interventions targeting points upstream from ART initiation along the continuum from infection to diagnosis to care engagement are needed.

The human-induced pluripotent stem cell initiative-data resources for cellular genetics.

Science.gov (United States)

Streeter, Ian; Harrison, Peter W; Faulconbridge, Adam; Flicek, Paul; Parkinson, Helen; Clarke, Laura

2017-01-04

The Human Induced Pluripotent Stem Cell Initiative (HipSci) isf establishing a large catalogue of human iPSC lines, arguably the most well characterized collection to date. The HipSci portal enables researchers to choose the right cell line for their experiment, and makes HipSci's rich catalogue of assay data easy to discover and reuse. Each cell line has genomic, transcriptomic, proteomic and cellular phenotyping data. Data are deposited in the appropriate EMBL-EBI archives, including the European Nucleotide Archive (ENA), European Genome-phenome Archive (EGA), ArrayExpress and PRoteomics IDEntifications (PRIDE) databases. The project will make 500 cell lines from healthy individuals, and from 150 patients with rare genetic diseases; these will be available through the European Collection of Authenticated Cell Cultures (ECACC). As of August 2016, 238 cell lines are available for purchase. Project data is presented through the HipSci data portal (http://www.hipsci.org/lines) and is downloadable from the associated FTP site (ftp://ftp.hipsci.ebi.ac.uk/vol1/ftp). The data portal presents a summary matrix of the HipSci cell lines, showing available data types. Each line has its own page containing descriptive metadata, quality information, and links to archived assay data. Analysis results are also available in a Track Hub, allowing visualization in the context of public genomic annotations (http://www.hipsci.org/data/trackhubs). © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Rural-urban differences in breastfeeding initiation in the United States.

Science.gov (United States)

Sparks, P Johnelle

2010-05-01

Research has noted a rural disadvantage in breastfeeding initiation; however, most previous research has been based on nonrepresentative samples and has been limited in its ability to compare racial/ethnic differences in breastfeeding initiation based on residential location. This research fills this gap by examining a nationally representative sample of births using the Early Childhood Longitudinal Study-Birth Cohort (ECLS-B) to explore associations between rural-urban residence and maternal race/ethnicity on breastfeeding initiation. Results indicate that associations observed for rural-urban breastfeeding initiation differ based on maternal race/ethnicity and poverty status. These patterns likely reflect differences in economic resources, work environments, and social support among rural minority postpartum women.

The DNA Inflammasome in Human Myeloid Cells Is Initiated by a STING-Cell Death Program Upstream of NLRP3

Science.gov (United States)

Gaidt, Moritz M.; Ebert, Thomas S.; Chauhan, Dhruv; Ramshorn, Katharina; Pinci, Francesca; Zuber, Sarah; O’Duill, Fionan; Schmid-Burgk, Jonathan L.; Hoss, Florian; Buhmann, Raymund; Wittmann, Georg; Latz, Eicke; Subklewe, Marion; Hornung, Veit

2018-01-01

Summary Detection of cytosolic DNA constitutes a central event in the context of numerous infectious and sterile inflammatory conditions. Recent studies have uncovered a bipartite mode of cytosolic DNA recognition, in which the cGAS-STING axis triggers antiviral immunity, whereas AIM2 triggers inflammasome activation. Here, we show that AIM2 is dispensable for DNA-mediated inflammasome activation in human myeloid cells. Instead, detection of cytosolic DNA by the cGAS-STING axis induces a cell death program initiating potassium efflux upstream of NLRP3. Forward genetics identified regulators of lysosomal trafficking to modulate this cell death program, and subsequent studies revealed that activated STING traffics to the lysosome, where it triggers membrane permeabilization and thus lysosomal cell death (LCD). Importantly, the cGAS-STING-NLRP3 pathway constitutes the default inflammasome response during viral and bacterial infections in human myeloid cells. We conclude that targeting the cGAS-STING-LCD-NLRP3 pathway will ameliorate pathology in inflammatory conditions that are associated with cytosolic DNA sensing. PMID:29033128

Donor exosomes rather than passenger leukocytes initiate alloreactive T cell responses after transplantation

Science.gov (United States)

Marino, Jose; Babiker-Mohamed, Mohamed H.; Crosby-Bertorini, Patrick; Paster, Joshua T.; LeGuern, Christian; Germana, Sharon; Abdi, Reza; Uehara, Mayuko; Kim, James I.; Markmann, James F.; Tocco, Georges; Benichou, Gilles

2016-01-01

Transplantation of allogeneic organs and tissues represents a lifesaving procedure for a variety of patients affected with end-stage diseases. Although current immunosuppressive therapy prevents early acute rejection, it is associated with nephrotoxicity and increased risks for infection and neoplasia. This stresses the need for selective immune-based therapies relying on manipulation of lymphocyte recognition of donor antigens. The passenger leukocyte theory states that allograft rejection is initiated by recipient T cells recognizing donor major histocompatibility complex (MHC) molecules displayed on graft leukocytes migrating to the host’s lymphoid organs. We revisited this concept in mice transplanted with allogeneic skin, heart, or islet grafts using imaging flow cytometry. We observed no donor cells in the lymph nodes and spleen of skin-grafted mice, but we found high numbers of recipient cells displaying allogeneic MHC molecules (cross-dressed) acquired from donor microvesicles (exosomes). After heart or islet transplantation, we observed few donor leukocytes (100 per million) but large numbers of recipient cells cross-dressed with donor MHC (>90,000 per million). Last, we showed that purified allogeneic exosomes induced proinflammatory alloimmune responses by T cells in vitro and in vivo. Collectively, these results suggest that recipient antigen-presenting cells cross-dressed with donor MHC rather than passenger leukocytes trigger T cell responses after allotransplantation. PMID:27942611

Fayette County Better Buildings Initiative

Energy Technology Data Exchange (ETDEWEB)

Capella, Arthur [County of Fayette, Uniontown, PA (United States)

2015-03-04

The Fayette County Better Buildings Initiative represented a comprehensive and collaborative approach to promoting and implementing energy efficiency improvements. The initiative was designed to focus on implementing energy efficiency improvements in residential units, while simultaneously supporting general marketing of the benefits of implementing energy efficiency measures. The ultimate goal of Fayette County’s Better Buildings Initiative was to implement a total of 1,067 residential energy efficiency retrofits with a minimum 15% estimated energy efficiency savings per unit. Program partners included: United States Department of Energy, Allegheny Power, and Private Industry Council of Westmoreland-Fayette, Fayette County Redevelopment Authority, and various local partners. The program was open to any Fayette County residents who own their home and meet the prequalifying conditions. The level of assistance offered depended upon household income and commitment to undergo a BPI – Certified Audit and implement energy efficiency measures, which aimed to result in at least a 15% reduction in energy usage. The initiative was designed to focus on implementing energy efficiency improvements in residential units, while simultaneously supporting general marketing of the benefits of implementing energy efficiency measures. Additionally, the program had components that involved recruitment and training for employment of persons in the energy sector (green jobs), as well as marketing and implementation of a commercial or community facilities component. The residential component of Fayette County’s Better Buildings Initiative involved a comprehensive approach, providing assistance to low- moderate- and market-rate homeowners. The initiative will also coordinate activities with local utility providers to further incentivize energy efficiency improvements among qualifying homeowners. The commercial component of Fayette County’s Better Building Initiative involved grants

Additively Manufactured Open-Cell Porous Biomaterials Made from Six Different Space-Filling Unit Cells : The Mechanical and Morphological Properties

NARCIS (Netherlands)

Ahmadi, S.M.; Yavari, S.A.; Wauthle, R.; Pouran, B.; Schrooten, J.; Weinans, H.; Zadpoor, A.A.

2015-01-01

It is known that the mechanical properties of bone-mimicking porous biomaterials are a function of the morphological properties of the porous structure, including the configuration and size of the repeating unit cell from which they are made. However, the literature on this topic is limited,

Alien species recorded in the United Arab Emirates: an initial list of terrestrial and freshwater species

Directory of Open Access Journals (Sweden)

Pritpal Soorae

2015-10-01

Full Text Available Little is documented on the alien terrestrial and freshwater species in the United Arab Emirates. To address this, an assessment of terrestrial and freshwater alien species was conducted using various techniques such as a questionnaire, fieldwork data, networking with relevant people, and a detailed literature review. The results of the initial assessment show that there are 146 alien species recorded in the following seven major taxonomic groups: invertebrates 49 species, freshwater fish five species, amphibian one species, reptiles six species, birds 71 species, mammals six species and plants eight species. To inform decision makers a full list of the 146 species identified in this assessment is presented. 

Branched chain amino acid suppressed insulin-initiated proliferation of human cancer cells through induction of autophagy.

Science.gov (United States)

Wubetu, Gizachew Yismaw; Utsunomiya, Tohru; Ishikawa, Daichi; Ikemoto, Tetsuya; Yamada, Shinichiro; Morine, Yuji; Iwahashi, Shuichi; Saito, Yu; Arakawa, Yusuke; Imura, Satoru; Arimochi, Hideki; Shimada, Mitsuo

2014-09-01

Branched chain amino acid (BCAA) dietary supplementation inhibits activation of the insulin-like growth factor (IGF)/IGF-I receptor (IGF-IR) axis in diabetic animal models. However, the in vitro effect of BCAA on human cancer cell lines under hyper-insulinemic conditions remains unclear. Colon (HCT-116) and hepatic (HepG2) tumor cells were treated with varying concentrations of BCAA with or without fluorouracil (5-FU). The effect of BCAA on insulin-initiated proliferation was determined. Gene and protein expression was analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting, respectively. BCAA supplementation had no significant effect on cell proliferation and did not show significant synergistic or antagonistic effects with 5-FU. However, BCAA significantly decreased insulin-initiated proliferation of human colon and hepatic cancer cell lines in vitro. BCAA supplementation caused a marked decrease in activated IGF-IR expression and significantly enhanced both mRNA and protein expression of LC3-II and BECN1 (BECLIN-1). BCAA could be a useful chemopreventive modality for cancer in hyperinsulinemic conditions. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

The United Nations Basic Space Science Initiative

Science.gov (United States)

Haubold, H. J.

2006-08-01

Pursuant to recommendations of the United Nations Conference on the Exploration and Peaceful Uses of Outer Space (UNISPACE III) and deliberations of the United Nations Committee on the Peaceful Uses of Outer Space (UNCOPUOS), annual UN/ European Space Agency workshops on basic space science have been held around the world since 1991. These workshops contribute to the development of astrophysics and space science, particularly in developing nations. Following a process of prioritization, the workshops identified the following elements as particularly important for international cooperation in the field: (i) operation of astronomical telescope facilities implementing TRIPOD, (ii) virtual observatories, (iii) astrophysical data systems, (iv) concurrent design capabilities for the development of international space missions, and (v) theoretical astrophysics such as applications of nonextensive statistical mechanics. Beginning in 2005, the workshops focus on preparations for the International Heliophysical Year 2007 (IHY2007). The workshops continue to facilitate the establishment of astronomical telescope facilities as pursued by Japan and the development of low-cost, ground-based, world-wide instrument arrays as lead by the IHY secretariat. Wamsteker, W., Albrecht, R. and Haubold, H.J.: Developing Basic Space Science World-Wide: A Decade of UN/ESA Workshops. Kluwer Academic Publishers, Dordrecht 2004. http://ihy2007.org http://www.unoosa.org/oosa/en/SAP/bss/ihy2007/index.html http://www.cbpf.br/GrupPesq/StatisticalPhys/biblio.htm

Assessment of Coping Capability of KORI Unit 1 under Extended Loss AC Power and Loss of Ultimate Heat Sink Initiated by Beyond Design Natural Disaster

Energy Technology Data Exchange (ETDEWEB)

Kim, Chang Hyun; Ha, Sang Jun [KHNP CRI, Daejeon (Korea, Republic of); Han, Kee Soo [Nuclear Engineering Service and Solution (NESS) Co. Ltd., Deajeon (Korea, Republic of); Park, Chan Eok [KEPCO Engineering and Constructd., Deajeon (Korea, Republic of)

2016-10-15

In Korea, the government and industry performed comprehensive safety inspection on all domestic nuclear power plants against beyond design basis external events and fifty action items have been issued. In addition to post- Fukushima action items, the stress tests for all domestic nuclear power plants are on the way to enhance the safety of domestic nuclear power plants through finding the vulnerabilities in intentional stress conditions initiated by beyond design natural disaster. This paper presents assessment results of coping capability of KORI Unit 1 under the simultaneous Extended Loss of AC Power (ELAP) and Loss of Ultimate Heat Sink (LUHS) which is a representative plant condition initiated by beyond design natural disaster. The assessment of the coping capability of KORI Unit 1 has been performed under simultaneous the extended loss of AC power and loss of ultimate heat sink initiated by beyond design natural disaster. It is concluded that KORI Unit 1 has the capability, in the event of loss of safety functions by beyond design natural disaster, to sufficiently cool down the reactor core without fuel damage, to keep pressure boundaries of the reactor coolant system in transient condition and to control containment and temperature to maintain the integrity of the containment buildings.

Assessment of Coping Capability of KORI Unit 1 under Extended Loss AC Power and Loss of Ultimate Heat Sink Initiated by Beyond Design Natural Disaster

International Nuclear Information System (INIS)

Kim, Chang Hyun; Ha, Sang Jun; Han, Kee Soo; Park, Chan Eok

2016-01-01

In Korea, the government and industry performed comprehensive safety inspection on all domestic nuclear power plants against beyond design basis external events and fifty action items have been issued. In addition to post- Fukushima action items, the stress tests for all domestic nuclear power plants are on the way to enhance the safety of domestic nuclear power plants through finding the vulnerabilities in intentional stress conditions initiated by beyond design natural disaster. This paper presents assessment results of coping capability of KORI Unit 1 under the simultaneous Extended Loss of AC Power (ELAP) and Loss of Ultimate Heat Sink (LUHS) which is a representative plant condition initiated by beyond design natural disaster. The assessment of the coping capability of KORI Unit 1 has been performed under simultaneous the extended loss of AC power and loss of ultimate heat sink initiated by beyond design natural disaster. It is concluded that KORI Unit 1 has the capability, in the event of loss of safety functions by beyond design natural disaster, to sufficiently cool down the reactor core without fuel damage, to keep pressure boundaries of the reactor coolant system in transient condition and to control containment and temperature to maintain the integrity of the containment buildings

Major design issues of molten carbonate fuel cell power generation unit

Energy Technology Data Exchange (ETDEWEB)

Chen, T.P.

1996-04-01

In addition to the stack, a fuel cell power generation unit requires fuel desulfurization and reforming, fuel and oxidant preheating, process heat removal, waste heat recovery, steam generation, oxidant supply, power conditioning, water supply and treatment, purge gas supply, instrument air supply, and system control. These support facilities add considerable cost and system complexity. Bechtel, as a system integrator of M-C Power`s molten carbonate fuel cell development team, has spent substantial effort to simplify and minimize these supporting facilities to meet cost and reliability goals for commercialization. Similiar to other fuels cells, MCFC faces design challenge of how to comply with codes and standards, achieve high efficiency and part load performance, and meanwhile minimize utility requirements, weight, plot area, and cost. However, MCFC has several unique design issues due to its high operating temperature, use of molten electrolyte, and the requirement of CO2 recycle.

3D-Printing Crystallographic Unit Cells for Learning Materials Science and Engineering

Science.gov (United States)

Rodenbough, Philip P.; Vanti, William B.; Chan, Siu-Wai

2015-01-01

Introductory materials science and engineering courses universally include the study of crystal structure and unit cells, which are by their nature highly visual 3D concepts. Traditionally, such topics are explored with 2D drawings or perhaps a limited set of difficult-to-construct 3D models. The rise of 3D printing, coupled with the wealth of…

Voltage-gated ion channels in the axon initial segment of human cortical pyramidal cells and their relationship with chandelier cells.

Science.gov (United States)

Inda, Maria Carmen; DeFelipe, Javier; Muñoz, Alberto

2006-02-21

The axon initial segment (AIS) of pyramidal cells is a critical region for the generation of action potentials and for the control of pyramidal cell activity. Here we show that Na+ and K+ voltage-gated channels, together with other molecules involved in the localization of ion channels, are distributed asymmetrically in the AIS of pyramidal cells situated in the human temporal neocortex. There is a high density of Na+ channels distributed along the length of the AIS together with the associated proteins spectrin betaIV and ankyrin G. In contrast, Kv1.2 channels are associated with the adhesion molecule Caspr2, and they are mostly localized to the distal region of the AIS. In general, the distal region of the AIS is targeted by the GABAergic axon terminals of chandelier cells, whereas the proximal region is innervated, mostly by other types of GABAergic interneurons. We suggest that this molecular segregation and the consequent regional specialization of the GABAergic input to the AIS of pyramidal cells may have important functional implications for the control of pyramidal cell activity.

Highly efficient elimination of colorectal tumor-initiating cells by an EpCAM/CD3-bispecific antibody engaging human T cells.

Directory of Open Access Journals (Sweden)

Ines Herrmann

2010-10-01

Full Text Available With their resistance to genotoxic and anti-proliferative drugs and potential to grow tumors and metastases from very few cells, cancer stem or tumor-initiating cells (TICs are a severe limitation for the treatment of cancer by conventional therapies. Here, we explored whether human T cells that are redirected via an EpCAM/CD3-bispecific antibody called MT110 can lyse colorectal TICs and prevent tumor growth from TICs. MT110 recognizes EpCAM, a cell adhesion molecule expressed on TICs from diverse human carcinoma, which was recently shown to promote tumor growth through engagement of elements of the wnt pathway. MT110 was highly potent in mediating complete redirected lysis of KRAS-, PI3 kinase- and BRAF-mutated colorectal TICs, as demonstrated in a soft agar assay. In immunodeficient mice, MT110 prevented growth of tumors from a 5,000-fold excess of a minimally tumorigenic TIC dose. T cells engaged by MT110 may provide a potent therapeutic means to eradicate TICs and bulk tumor cells derived thereof.

CD73 Regulates Stemness and Epithelial-Mesenchymal Transition in Ovarian Cancer-Initiating Cells.

Science.gov (United States)

Lupia, Michela; Angiolini, Francesca; Bertalot, Giovanni; Freddi, Stefano; Sachsenmeier, Kris F; Chisci, Elisa; Kutryb-Zajac, Barbara; Confalonieri, Stefano; Smolenski, Ryszard T; Giovannoni, Roberto; Colombo, Nicoletta; Bianchi, Fabrizio; Cavallaro, Ugo

2018-04-10

Cancer-initiating cells (CICs) have been implicated in tumor development and aggressiveness. In ovarian carcinoma (OC), CICs drive tumor formation, dissemination, and recurrence, as well as drug resistance, thus accounting for the high death-to-incidence ratio of this neoplasm. However, the molecular mechanisms that underlie such a pathogenic role of ovarian CICs (OCICs) remain elusive. Here, we have capitalized on primary cells either from OC or from its tissues of origin to obtain the transcriptomic profile associated with OCICs. Among the genes differentially expressed in OCICs, we focused on CD73, which encodes the membrane-associated 5'-ectonucleotidase. The genetic inactivation of CD73 in OC cells revealed that this molecule is causally involved in sphere formation and tumor initiation, thus emerging as a driver of OCIC function. Furthermore, functional inhibition of CD73 via either a chemical compound or a neutralizing antibody reduced sphere formation and tumorigenesis, highlighting the druggability of CD73 in the context of OCIC-directed therapies. The biological function of CD73 in OCICs required its enzymatic activity and involved adenosine signaling. Mechanistically, CD73 promotes the expression of stemness and epithelial-mesenchymal transition-associated genes, implying a regulation of OCIC function at the transcriptional level. CD73, therefore, is involved in OCIC biology and may represent a therapeutic target for innovative treatments aimed at OC eradication. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

CLIMATE CHANGE FUEL CELL PROGRAM UNITED STATES COAST GUARD AIR STATION CAPE COD BOURNE, MASSACHUSETTS

Energy Technology Data Exchange (ETDEWEB)

John K. Steckel Jr

2004-06-30

This report covers the first year of operation of a fuel cell power plant, installed by PPL Spectrum, Inc. (PPL) under contract with the United States Coast Guard (USCG), Research and Development Center (RDC). The fuel cell was installed at Air Station Cape Cod in Bourne, MA. The project had the support of the Massachusetts Technology Collaborative (MTC), the Department of Energy (DOE), and Keyspan Energy. PPL selected FuelCell Energy, Inc. (FCE) and its fuel cell model DFC{reg_sign}300 for the contract. Grant contributions were finalized and a contract between PPL and the USCG for the manufacture, installation, and first year's maintenance of the fuel cell was executed on September 24, 2001. As the prime contractor, PPL was responsible for all facets of the project. All the work was completed by PPL through various subcontracts, including the primary subcontract with FCE for the manufacture, delivery, and installation of the fuel cell. The manufacturing and design phases proceeded in a relatively timely manner for the first half of the project. However, during latter stages of manufacture and fuel cell testing, a variety of issues were encountered that ultimately resulted in several delivery delays, and a number of contract modifications. Final installation and field testing was completed in April and May 2003. Final acceptance of the fuel cell was completed on May 16, 2003. The fuel cell has operated successfully for more than one year. The unit achieved an availability rate of 96%, which exceeded expectations. The capacity factor was limited because the unit was set at 155 kW (versus a nameplate of 250 kW) due to the interconnection with the electric utility. There were 18 shutdowns during the first year and most were brief. The ability of this plant to operate in the island mode improved availability by 3 to 4%. Events that would normally be shutdowns were simply island mode events. The mean time between failure was calculated at 239 hours, or slightly

On the Effect of Unit-Cell Parameters in Predicting the Elastic Response of Wood-Plastic Composites

Directory of Open Access Journals (Sweden)

Fatemeh Alavi

2013-01-01

Full Text Available This paper presents a study on the effect of unit-cell geometrical parameters in predicting elastic properties of a typical wood plastic composite (WPC. The ultimate goal was obtaining the optimal values of representative volume element (RVE parameters to accurately predict the mechanical behavior of the WPC. For each unit cell, defined by a given combination of the above geometrical parameters, finite element simulation in ABAQUS was carried out, and the corresponding stress-strain curve was obtained. A uniaxial test according to ASTM D638-02a type V was performed on the composite specimen. Modulus of elasticity was determined using hyperbolic tangent function, and the results were compared to the sets of finite element analyses. Main effects of RVE parameters and their interactions were demonstrated and discussed, specially regarding the inclusion of two adjacent wood particles within one unit cell of the material. Regression analysis was performed to mathematically model the RVE parameter effects and their interactions over the modulus of elasticity response. The model was finally employed in an optimization analysis to arrive at an optimal set of RVE parameters that minimizes the difference between the predicted and experimental moduli of elasticity.

Elimination of head and neck cancer initiating cells through targeting glucose regulated protein78 signaling

Directory of Open Access Journals (Sweden)

Huang Chih-Yang

2010-10-01

Full Text Available Abstract Background Head and neck squamous cell carcinoma (HNSCC is a highly lethal cancer that contains cellular and functional heterogeneity. Previously, we enriched a subpopulation of highly tumorigenic head and neck cancer initiating cells (HN-CICs from HNSCC. However, the molecular mechanisms by which to govern the characteristics of HN-CICs remain unclear. GRP78, a stress-inducible endoplasmic reticulum chaperone, has been reported to play a crucial role in the maintenance of embryonic stem cells, but the role of GRP78 in CICs has not been elucidated. Results Initially, we recognized GRP78 as a putative candidate on mediating the stemness and tumorigenic properties of HN-CICs by differential systemic analyses. Subsequently, cells with GRP78 anchored at the plasma membrane (memGRP78+ exerted cancer stemness properties of self-renewal, differentiation and radioresistance. Of note, xenotransplantation assay indicated merely 100 memGRP78+ HNSCCs resulted in tumor growth. Moreover, knockdown of GRP78 significantly reduced the self-renewal ability, side population cells and expression of stemness genes, but inversely promoted cell differentiation and apoptosis in HN-CICs. Targeting GRP78 also lessened tumorigenicity of HN-CICs both in vitro and in vivo. Clinically, co-expression of GRP78 and Nanog predicted the worse survival prognosis of HNSCC patients by immunohistochemical analyses. Finally, depletion of GRP78 in HN-CICs induced the expression of Bax, Caspase 3, and PTEN. Conclusions In summary, memGRP78 should be a novel surface marker for isolation of HN-CICs, and targeting GRP78 signaling might be a potential therapeutic strategy for HNSCC through eliminating HN-CICs.

In vitro assays for cobblestone area-forming cells, LTC-IC, and CFU-C

NARCIS (Netherlands)

van Os, Ronald P; Dethmers-Ausema, Bertien; de Haan, Gerald; Bunting, Kevin

2008-01-01

Various assays exist that measure the function of hematopoietic stemcells (HSCs). In this chapter, in vitro assays are described that measure the frequency of progenitors (colony-forming unit in culture; CFU-C), stem cells (long-term culture-initiating cell; LTC-IC), or both (cobblestone

Use of variations in unit cell length, reflectance and hardness for determining the origin of Fe disulphides in sedimentary rocks

Science.gov (United States)

Dill, H. G.; Eberhard, E.; Hartmann, B.

1997-01-01

Fe disulphides are common opaque accessories in sedimentary rocks. Both marcasite and pyrite may shed some light on the depositional environment and help determine the diagenesis of their host rocks. Quantitative ore microscopy (reflectance measurements, Vickers hardness numbers) and X-ray diffraction methods, supplemented with scanning electron microscopy and chemical analyses, were applied to pyrite (and some marcasite) hosted by sedimentary rocks spanning the interval from the Devonian to the Pliocene, and formed in various marine and continental environments. Quantitative ore microscopy of pyrites of sedimentary origin does not seem to be an efficient tool for analyzing the environment owing to the inhomogeneous nature of sulphide aggregates when viewed under the ore microscope, and the variable amounts of minor elements (e.g., As, Ni, and Co) that control the reflectance values (RV) and Vickers hardness numbers (VHN) of the host sulphides. However, such parameters as crystal habit and unit cell length of pyrite, which correlate with FeS x, are useful for environmental analysis. The redox conditions and the presence of organic remains during formation are the main factors determining these crystallographic parameters. Differences in these parameters from those of pure, ideal FeS 2 can be related to substitution of, e.g., wustite in the pyrite lattice, reflecting moderate oxidation (i.e. in the microenvironment). As far as crystal habit and length of the cell edge are concerned, late stage diagenesis is obviously less important than the microenvironment attending initial formation. The environment of deposition (i.e. the macroenvironment) of pyrite-bearing rocks has no influence on the crystal morphology or the length of the unit cell of Fe disulphide. X-ray diffraction measurements demonstrate that this method provides useful evidence on the microenvironment of sulphide precipitation around a single, equant pyrite, as well as around pyritized fossils.

Generation, isolation, and maintenance of rodent mast cells and mast cell lines

DEFF Research Database (Denmark)

Jensen, Bettina M; Swindle, Emily J; Iwaki, Shoko

2006-01-01

Antigen-mediated mast cell activation, with subsequent mediator release, is a major initiator of the inflammatory allergic response associated with such conditions as asthma. A comprehensive understanding of the principles involved in this process therefore is key to the development of novel...... therapies for the treatment of these disease states. In vitro models of mast cell function have allowed significant progress to be made in the recognition of the fundamental principles of mast cell activation via the high-affinity IgE receptor (FcvarepsilonRI) and, more recently, other receptors expressed...... on mast cells. In addition to human mast cells, the major cell culture systems employed to investigate these responses are rat and mouse peritoneal mast cells, mouse bone-marrow-derived mast cells, the rat basophilic leukemia cell line RBL-2H3, and the mouse MC/9 mast cell line. In this unit, we describe...

Co-Transcriptomes of Initial Interactions In Vitro between Streptococcus Pneumoniae and Human Pleural Mesothelial Cells.

Directory of Open Access Journals (Sweden)

Claire J Heath

Full Text Available Streptococcus pneumoniae (Spn is a major causative organism of empyema, an inflammatory condition occurring in the pleural sac. In this study, we used human and Spn cDNA microarrays to characterize the transcriptional responses occurring during initial contact between Spn and a human pleural mesothelial cell line (PMC in vitro. Using stringent filtering criteria, 42 and 23 Spn genes were up-and down-regulated respectively. In particular, genes encoding factors potentially involved in metabolic processes and Spn adherence to eukaryotic cells were up-regulated e.g. glnQ, glnA, aliA, psaB, lytB and nox. After Spn initial contact, 870 human genes were differentially regulated and the largest numbers of significant gene expression changes were found in canonical pathways for eukaryotic initiation factor 2 signaling (60 genes out of 171, oxidative phosphorylation (32/103, mitochondrial dysfunction (37/164, eIF4 and p70S6K signaling (28/142, mTOR signaling (27/182, NRF2-mediated oxidative stress response (20/177, epithelial adherens junction remodeling (11/66 and ubiquitination (22/254. The cellular response appeared to be directed towards host cell survival and defense. Spn did not activate NF-kB or phosphorylate p38 MAPK or induce cytokine production from PMC. Moreover, Spn infection of TNF-α pre-stimulated PMC inhibited production of IL-6 and IL-8 secretion by >50% (p<0.01. In summary, this descriptive study provides datasets and a platform for examining further the molecular mechanisms underlying the pathogenesis of empyema.

Integrated Advanced Microwave Sounding Unit-A (AMSU-A). Performance Verification Report: Initial Comprehensive Performance Test Report, P/N 1331200-2-IT, S/N 105/A2

Science.gov (United States)

Platt, R.

1999-01-01

This is the Performance Verification Report, Initial Comprehensive Performance Test Report, P/N 1331200-2-IT, S/N 105/A2, for the Integrated Advanced Microwave Sounding Unit-A (AMSU-A). The specification establishes the requirements for the Comprehensive Performance Test (CPT) and Limited Performance Test (LPT) of the Advanced Microwave Sounding, Unit-A2 (AMSU-A2), referred to herein as the unit. The unit is defined on Drawing 1331200. 1.2 Test procedure sequence. The sequence in which the several phases of this test procedure shall take place is shown in Figure 1, but the sequence can be in any order.

Molten Salt Breeder Reactor Analysis Based on Unit Cell Model

Energy Technology Data Exchange (ETDEWEB)

Jeong, Yongjin; Choi, Sooyoung; Lee, Deokjung [Ulsan National Institute of Science and Technology, Ulsan (Korea, Republic of)

2014-05-15

Contemporary computer codes like the MCNP6 or SCALE are only good for solving a fixed solid fuel reactor. However, due to the molten-salt fuel, MSR analysis needs some functions such as online reprocessing and refueling, and circulating fuel. J. J. Power of Oak Ridge National Laboratory (ORNL) suggested in 2013 a method for simulating the Molten Salt Breeder Reactor (MSBR) with SCALE, which does not support continuous material processing. In order to simulate MSR characteristics, the method proposes dividing a depletion time into short time intervals and batchwise reprocessing and refueling at each step. We are applying this method by using the MCNP6 and PYTHON and NEWT-TRITON-PYTHON and PYTHON code systems to MSBR. This paper contains various parameters to analyze the MSBR unit cell model such as the multiplication factor, breeding ratio, change of amount of fuel, amount of fuel feeding, and neutron flux distribution. The result of MCNP6 and NEWT module in SCALE show some difference in depletion analysis, but it still seems that they can be used to analyze MSBR. Using these two computer code system, it is possible to analyze various parameters for the MSBR unit cells such as the multiplication factor, breeding ratio, amount of material, total feeding, and neutron flux distribution. Furthermore, the two code systems will be able to be used for analyzing other MSR model or whole core models of MSR.

Molten Salt Breeder Reactor Analysis Based on Unit Cell Model

International Nuclear Information System (INIS)

Jeong, Yongjin; Choi, Sooyoung; Lee, Deokjung

2014-01-01

Contemporary computer codes like the MCNP6 or SCALE are only good for solving a fixed solid fuel reactor. However, due to the molten-salt fuel, MSR analysis needs some functions such as online reprocessing and refueling, and circulating fuel. J. J. Power of Oak Ridge National Laboratory (ORNL) suggested in 2013 a method for simulating the Molten Salt Breeder Reactor (MSBR) with SCALE, which does not support continuous material processing. In order to simulate MSR characteristics, the method proposes dividing a depletion time into short time intervals and batchwise reprocessing and refueling at each step. We are applying this method by using the MCNP6 and PYTHON and NEWT-TRITON-PYTHON and PYTHON code systems to MSBR. This paper contains various parameters to analyze the MSBR unit cell model such as the multiplication factor, breeding ratio, change of amount of fuel, amount of fuel feeding, and neutron flux distribution. The result of MCNP6 and NEWT module in SCALE show some difference in depletion analysis, but it still seems that they can be used to analyze MSBR. Using these two computer code system, it is possible to analyze various parameters for the MSBR unit cells such as the multiplication factor, breeding ratio, amount of material, total feeding, and neutron flux distribution. Furthermore, the two code systems will be able to be used for analyzing other MSR model or whole core models of MSR

Outlines of a general theory of cancer initiation in the cell

Energy Technology Data Exchange (ETDEWEB)

Ladik, J.J. [Friedrich Alexander Univ. Erlangen-Nuremberg, Erlangen (Germany)

1996-12-31

According to the central dogma of molecular biology information flows in the living cell from DNA through RNA to proteins. Therefore most investigations of cancer initiation try to explain those effects of carcinogen binding to- or radiation hits on DNA which lead to the first steps of the malignant transformations. On the other hand recent detailed theoretical investigations have shown that proteins are good-disordered hopping conductors (their conductivity is in the order of well conducting amorphous glasses). Their conductivity is substantially influenced by binding of chemicals or by effects or radiations causing conformational changes and/or destroying bonds in them which can lead to their inactivation as regulation enzymes. One can easily visualize also how such changes become hereditary. It seems that if we look at the cell as a complicated self-regulatory system, primary changes both at their DNA or regulatory protein molecules caused by external agents can disturb its self-regulation and transform it in this way into another stationary, possibly precancerous state.

Increased numbers of spleen colony forming units in B cell deficient CBA/N mice

International Nuclear Information System (INIS)

Wiktor-Jedrzejczak, W.; Krupienicz, A.; Scher, I.

1986-01-01

The formation of exogenous and endogenous spleen colonies was studied in immune-defective mice expressing the CBA/N X-linked xid gene. Bone marrow and spleen cells of immune deficient mice formed increased numbers of eight-day exogenous spleen colonies when transferred to either normal or B cell deficient lethally irradiated recipients. Moreover, defective mice showed increased formation of five-day endogenous spleen colonies (derived from transient endogenous colony forming units; T-CFU) and of ten-day endogenous spleen colonies (derived from CFU-S). Among the possible mechanisms responsible for the observed effects, the most probable appears the one in which decreased numbers of B cell precursors stimulate stem cell pools through a feedback mechanism. (orig.) [de

Medical societies, patient education initiatives, public debate and marketing of unproven stem cell interventions.

Science.gov (United States)

Weiss, Daniel J; Turner, Leigh; Levine, Aaron D; Ikonomou, Laertis

2018-02-01

Businesses marketing unproven stem cell interventions proliferate within the U.S. and in the larger global marketplace. There have been global efforts by scientists, patient advocacy groups, bioethicists, and public policy experts to counteract the uncontrolled and premature commercialization of stem cell interventions. In this commentary, we posit that medical societies and associations of health care professionals have a particular responsibility to be an active partner in such efforts. We review the role medical societies can and should play in this area through patient advocacy and awareness initiatives. Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Precursor States of Brain Tumor Initiating Cell Lines Are Predictive of Survival in Xenografts and Associated with Glioblastoma Subtypes

Directory of Open Access Journals (Sweden)

Carlo Cusulin

2015-07-01

Full Text Available In glioblastoma multiforme (GBM, brain-tumor-initiating cells (BTICs with cancer stem cell characteristics have been identified and proposed as primordial cells responsible for disease initiation, recurrence, and therapeutic resistance. However, the extent to which individual, patient-derived BTIC lines reflect the heterogeneity of GBM remains poorly understood. Here we applied a stem cell biology approach and compared self-renewal, marker expression, label retention, and asymmetric cell division in 20 BTIC lines. Through cluster analysis, we identified two subgroups of BTIC lines with distinct precursor states, stem- or progenitor-like, predictive of survival after xenograft. Moreover, stem and progenitor transcriptomic signatures were identified, which showed a strong association with the proneural and mesenchymal subtypes, respectively, in the TCGA cohort. This study proposes a different framework for the study and use of BTIC lines and provides precursor biology insights into GBM.

PKC δ Regulates Translation Initiation through PKR and eIF2 α in Response to Retinoic Acid in Acute Myeloid Leukemia Cells

OpenAIRE

Ozpolat, Bulent; Akar, Ugur; Tekedereli, Ibrahim; Alpay, S. Neslihan; Barria, Magaly; Gezgen, Baki; Zhang, Nianxiang; Coombes, Kevin; Kornblau, Steve; Lopez-Berestein, Gabriel

2012-01-01

Translation initiation and activity of eukaryotic initiation factor-alpha (eIF2 α ), the rate-limiting step of translation initiation, is often overactivated in malignant cells. Here, we investigated the regulation and role of eIF2 α in acute promyelocytic (APL) and acute myeloid leukemia (AML) cells in response to all-trans retinoic acid (ATRA) and arsenic trioxide (ATO), the front-line therapies in APL. ATRA and ATO induce Ser-51 phosphorylation (inactivation) of eIF2 α , through the induct...

Canada-United States-Mexico Trilateral Cooperation on Childhood Obesity Initiative.

Science.gov (United States)

Rabadán-Diehl, Cristina; Safdie, Margarita; Rodin, Rachel

2016-08-01

Childhood obesity is an important public health problem that affects countries in the Americas. In 2014, Pan American Health Organization (PAHO) Member States agreed on a Plan of Action for the Prevention of Obesity in Children and Adolescents in an effort to address the impact of this disorder in the Americas region. The interventions laid out in this regional plan are multi-faceted and require multi-sectoral partnerships. Building on a strong history of successful trilateral collaboration, Canada, Mexico, and the United States formed a partnership to address the growing epidemic of childhood obesity in the North American region. This collaborative effort, known as the Trilateral Cooperation on Childhood Obesity Initiative, is the first initiative in the region to address chronic noncommunicable diseases by bringing together technical and policy experts, with strong leadership and support from the secretaries and ministers of health. The Initiative's goals include increasing levels of physical activity and reducing sedentary behavior through 1) increased social mobilization and citizen engagement, 2) community- based outreach, and 3) changes to the built (man-made) environment. This article describes the background and development process of the Initiative; specific goals, activities, and actions achieved to date; and opportunities and next steps. This information may be useful for those forming other partnerships designed to address childhood obesity or other complex public health challenges in the region. RESUMEN La obesidad infantil es un problema de salud pública importante que afecta a los países de las Américas. En el 2014, los Estados Miembros de la Organización Panamericana de la Salud (OPS) acordaron un Plan de acción para la prevención de la obesidad en la niñez y la adolescencia con el fin de hacer frente a las repercusiones de este trastorno en la Región de las Américas. Las intervenciones que componen este plan regional son multifacéticas y

CD274 promotes cell cycle entry of leukemia-initiating cells through JNK/Cyclin D2 signaling

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Xia Fang

2016-11-01

Full Text Available Abstract Background CD274 (programmed death ligand 1, also known as B7H1 is expressed in both solid tumors and hematologic malignancies and is of critical importance for the escape of tumor cells from immune surveillance by inhibiting T cell function via its receptor, programmed death 1 (PD-1. Increasing evidence indicates that functional monoclonal antibodies of CD274 may potently enhance the antitumor effect in many cancers. However, the role of CD274 in leukemia-initiating cells (LICs remains largely unknown. Methods We established an MLL-AF9-induced acute myeloid leukemia (AML model with wild-type (WT and CD274-null mice to elucidate the role of CD274 in the cell fates of LICs, including self-renewal, differentiation, cell cycle, and apoptosis. RNA sequencing was performed to reveal the potential downstream targets, the results of which were further validated both in vitro and in vivo. Results In silico analysis indicated that CD274 level was inversely correlated with the overall survival of AML patients. In Mac-1+/c-Kit+ mouse LICs, CD274 was expressed at a much higher level than in the normal hematopoietic stem cells (HSCs. The survival of the mice with CD274-null leukemia cells was dramatically extended during the serial transplantation compared with that of their WT counterparts. CD274 deletion led to a significant decrease in LIC frequency and arrest in the G1 phase of the cell cycle. Interestingly, CD274 is not required for the maintenance of HSC pool as shown in our previous study. Mechanistically, we demonstrated that the levels of both phospho-JNK and Cyclin D2 were strikingly downregulated in CD274-null LICs. The overexpression of Cyclin D2 fully rescued the loss of function of CD274. Moreover, CD274 was directly associated with JNK and enhanced the downstream signaling to increase the Cyclin D2 level, promoting leukemia development. Conclusions The surface immune molecule CD274 plays a critical role in the proliferation of LICs

Dealing with initial chemotherapy doses: a new basis for treatment optimization in limited small-cell lung cancer

International Nuclear Information System (INIS)

Le Chevalier, T.; Le Cesne, A.; Arriagada, R.

1995-01-01

Treatment of patients with small-cell lung cancer (SCLC) remains disappointing despite high initial complete response rates. The dramatic initial chemosensitivity of tumor cells is frustrated by the early emergence of chemoresistant clonogenic cells, regardless of front line treatments. Although the dose relationship is fairly well established regarding the response rate, its effect on survival is inconclusive. From 1980 to 1988, 202 patients with limited SCLC were included in four consecutive protocols using an alternating schedule of thoracic radiotherapy and chemotherapy. Despite an increase of chemotherapy and/or total radiation doses, no significant difference was observed between the four protocols in terms of response rate, disease free and overall survival. However, a retrospective analysis performed on a total of 131 consecutive patients led us to propose the hypothesis that a moderate increase in the initial dose, ie first course, of cisplatin and cyclophosphamide could improve overall survival. From 1988 to 1991, 105 patients were subsequently included in a large randomized trial raising this question. The treatment difference only concerned the initial doses of cisplatin (80 vs 100 mg/m 2 ) and cyclophosphamide (900 vs 1200 mg/m 2 ). The trial was closed after inclusion of 105 patients, 32 months after the start of the study because at that time overall survival was significantly better in the higher-dose group (p = 0.001). The emergence of this debatable concept opens new directions in the therapeutic strategy of SCLC and the contribution of hematopoietic growth factors may be a great interest in the management of this disease. (authors). 27 refs., 1 tab

Live-cell imaging of conidial anastomosis tube fusion during colony initiation in Fusarium oxysporum.

Directory of Open Access Journals (Sweden)

Smija M Kurian

Full Text Available Fusarium oxysporum exhibits conidial anastomosis tube (CAT fusion during colony initiation to form networks of conidial germlings. Here we determined the optimal culture conditions for this fungus to undergo CAT fusion between microconidia in liquid medium. Extensive high resolution, confocal live-cell imaging was performed to characterise the different stages of CAT fusion, using genetically encoded fluorescent labelling and vital fluorescent organelle stains. CAT homing and fusion were found to be dependent on adhesion to the surface, in contrast to germ tube development which occurs in the absence of adhesion. Staining with fluorescently labelled concanavalin A indicated that the cell wall composition of CATs differs from that of microconidia and germ tubes. The movement of nuclei, mitochondria, vacuoles and lipid droplets through fused germlings was observed by live-cell imaging.

Theoretical characterization and design of small molecule donor material containing naphthodithiophene central unit for efficient organic solar cells.

Science.gov (United States)

Duan, Yu-Ai; Geng, Yun; Li, Hai-Bin; Jin, Jun-Ling; Wu, Yong; Su, Zhong-Min

2013-07-15

To seek for high-performance small molecule donor materials used in heterojunction solar cell, six acceptor-donor-acceptor small molecules based on naphtho[2,3-b:6,7-b']dithiophene (NDT) units with different acceptor units were designed and characterized using density functional theory and time-dependent density functional theory. Their geometries, electronic structures, photophysical, and charge transport properties have been scrutinized comparing with the reported donor material NDT(TDPP)2 (TDPP  =  thiophene-capped diketopyrrolopyrrole). The open circuit voltage (V(oc)), energetic driving force(ΔE(L-L)), and exciton binding energy (E(b)) were also provided to give an elementary understanding on their cell performance. The results reveal that the frontier molecular orbitals of 3-7 match well with the acceptor material PC61 BM, and compounds 3-5 were found to exhibit the comparable performances to 1 and show promising potential in organic solar cells. In particular, comparing with 1, system 7 with naphthobisthiadiazole acceptor unit displays broader absorption spectrum, higher V(oc), lower E(b), and similar carrier mobility. An in-depth insight into the nature of the involved excited states based on transition density matrix and charge density difference indicates that all S1 states are mainly intramolecular charge transfer states with the charge transfer from central NDT unit to bilateral acceptor units, and also imply that the exciton of 7 can be dissociated easily due to its large extent of the charge transfer. In a word, 7 maybe superior to 1 and may act as a promising donor candidate for organic solar cell. Copyright © 2013 Wiley Periodicals, Inc.

Report of the International Stem Cell Banking Initiative Workshop Activity: Current Hurdles and Progress in Seed-Stock Banking of Human Pluripotent Stem Cells.

Science.gov (United States)

Kim, Jung-Hyun; Kurtz, Andreas; Yuan, Bao-Zhu; Zeng, Fanyi; Lomax, Geoff; Loring, Jeanne F; Crook, Jeremy; Ju, Ji Hyeon; Clarke, Laura; Inamdar, Maneesha S; Pera, Martin; Firpo, Meri T; Sheldon, Michael; Rahman, Nafees; O'Shea, Orla; Pranke, Patricia; Zhou, Qi; Isasi, Rosario; Rungsiwiwut, Ruttachuk; Kawamata, Shin; Oh, Steve; Ludwig, Tenneille; Masui, Tohru; Novak, Thomas J; Takahashi, Tsuneo; Fujibuchi, Wataru; Koo, Soo Kyung; Stacey, Glyn N

2017-11-01

This article summarizes the recent activity of the International Stem Cell Banking Initiative (ISCBI) held at the California Institute for Regenerative Medicine (CIRM) in California (June 26, 2016) and the Korean National Institutes for Health in Korea (October 19-20, 2016). Through the workshops, ISCBI is endeavoring to support a new paradigm for human medicine using pluripotent stem cells (hPSC) for cell therapies. Priority considerations for ISCBI include ensuring the safety and efficacy of a final cell therapy product and quality assured source materials, such as stem cells and primary donor cells. To these ends, ISCBI aims to promote global harmonization on quality and safety control of stem cells for research and the development of starting materials for cell therapies, with regular workshops involving hPSC banking centers, biologists, and regulatory bodies. Here, we provide a brief overview of two such recent activities, with summaries of key issues raised. Stem Cells Translational Medicine 2017;6:1956-1962. © 2017 The Authors Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

Career Technical Education Pathways Initiative

Science.gov (United States)

California Community Colleges, Chancellor's Office, 2013

2013-01-01

California's education system--the largest in the United States--is an essential resource for ensuring strong economic growth in the state. The Career Technical Education Pathways Initiative (referred to as the Initiative in this report), which became law in 2005, brings together community colleges, K-12 school districts, employers, organized…

A heated vapor cell unit for dichroic atomic vapor laser lock in atomic rubidium.

Science.gov (United States)

McCarron, Daniel J; Hughes, Ifan G; Tierney, Patrick; Cornish, Simon L

2007-09-01

The design and performance of a compact heated vapor cell unit for realizing a dichroic atomic vapor laser lock (DAVLL) for the D(2) transitions in atomic rubidium is described. A 5 cm long vapor cell is placed in a double-solenoid arrangement to produce the required magnetic field; the heat from the solenoid is used to increase the vapor pressure and correspondingly the DAVLL signal. We have characterized experimentally the dependence of important features of the DAVLL signal on magnetic field and cell temperature. For the weaker transitions both the amplitude and gradient of the signal are increased by an order of magnitude.

A heated vapor cell unit for dichroic atomic vapor laser lock in atomic rubidium

International Nuclear Information System (INIS)

McCarron, Daniel J.; Hughes, Ifan G.; Tierney, Patrick; Cornish, Simon L.

2007-01-01

The design and performance of a compact heated vapor cell unit for realizing a dichroic atomic vapor laser lock (DAVLL) for the D 2 transitions in atomic rubidium is described. A 5 cm long vapor cell is placed in a double-solenoid arrangement to produce the required magnetic field; the heat from the solenoid is used to increase the vapor pressure and correspondingly the DAVLL signal. We have characterized experimentally the dependence of important features of the DAVLL signal on magnetic field and cell temperature. For the weaker transitions both the amplitude and gradient of the signal are increased by an order of magnitude

High quality-factor fano metasurface comprising a single resonator unit cell

Science.gov (United States)

Sinclair, Michael B.; Warne, Larry K.; Basilio, Lorena I.; Langston, William L.; Campione, Salvatore; Brener, Igal; Liu, Sheng

2017-06-20

A new monolithic resonator metasurface design achieves ultra-high Q-factors while using only one resonator per unit cell. The metasurface relies on breaking the symmetry of otherwise highly symmetric resonators to induce intra-resonator mixing of bright and dark modes (rather than inter-resonator couplings), and is scalable from the near-infrared to radio frequencies and can be easily implemented in dielectric materials. The resulting high-quality-factor Fano metasurface can be used in many sensing, spectral filtering, and modulation applications.

SIRT6 knockout cells resist apoptosis initiation but not progression: a computational method to evaluate the progression of apoptosis.

Science.gov (United States)

Domanskyi, Sergii; Nicholatos, Justin W; Schilling, Joshua E; Privman, Vladimir; Libert, Sergiy

2017-11-01

Apoptosis is essential for numerous processes, such as development, resistance to infections, and suppression of tumorigenesis. Here, we investigate the influence of the nutrient sensing and longevity-assuring enzyme SIRT6 on the dynamics of apoptosis triggered by serum starvation. Specifically, we characterize the progression of apoptosis in wild type and SIRT6 deficient mouse embryonic fibroblasts using time-lapse flow cytometry and computational modelling based on rate-equations and cell distribution analysis. We find that SIRT6 deficient cells resist apoptosis by delaying its initiation. Interestingly, once apoptosis is initiated, the rate of its progression is higher in SIRT6 null cells compared to identically cultured wild type cells. However, SIRT6 null cells succumb to apoptosis more slowly, not only in response to nutrient deprivation but also in response to other stresses. Our data suggest that SIRT6 plays a role in several distinct steps of apoptosis. Overall, we demonstrate the utility of our computational model to describe stages of apoptosis progression and the integrity of the cellular membrane. Such measurements will be useful in a broad range of biological applications.

Identification of two distinct chromosome 12-derived amplification units in neuroblastoma cell line NGP

NARCIS (Netherlands)

van Roy, N.; Forus, A.; Myklebost, O.; Cheng, N. C.; Versteeg, R.; Speleman, F.

1995-01-01

The neuroblastoma cell line NGP contains two homogeneously staining regions (hsr). One of these hsrs contains MYCN sequences. Reverse painting experiments demonstrated that the second HSR consisted of two chromosome 12-derived amplification units, located at 12q14-15 and 12q24. Southern blot and

Groundwater quality data in 15 GAMA study units: results from the 2006–10 Initial sampling and the 2009–13 resampling of wells, California GAMA Priority Basin Project

Science.gov (United States)

Kent, Robert

2015-08-31

The Priority Basin Project (PBP) of the Groundwater Ambient Monitoring and Assessment (GAMA) program was developed in response to the Groundwater Quality Monitoring Act of 2001 and is being conducted by the U.S. Geological Survey (USGS) in cooperation with the California State Water Resources Control Board (SWRCB). From May 2004 to March 2012, the GAMA-PBP collected samples from more than 2,300 wells in 35 study units across the State. Selected wells in each study unit were sampled again approximately 3 years after initial sampling as part of an assessment of temporal trends in water quality by the GAMA-PBP. This triennial (every 3 years) trend sampling of GAMA-PBP study units concluded in December 2013. Fifteen of the study units, initially sampled between January 2006 and June 2010 and sampled a second time between April 2009 and April 2013 to assess temporal trends, are the subject of this report.

Therapeutic Outcome of Extranodal NK/T-Cell Lymphoma Initially Treated with Chemotherapy

Energy Technology Data Exchange (ETDEWEB)

Kim, Byung Su; Kim, Tae-you; Kim, Chul Woo; Kim, Ji Yeun; Heo, Dae Seog; Bang, Yung-jue; Kim, Noe Kyeong [Seoul National Univ. College of Medicine (Korea, Republic of). Cancer Research Inst.

2003-11-01

The therapeutic outcome of chemotherapy in NK/T cell lymphoma (NTCL) has not been well documented until now. The aims of this study were to investigate the outcome of chemotherapy and to evaluate the clinical factors influencing the responsiveness to chemotherapy. Between 1995 and 2000, 59 patients received anthracycline-based chemotherapy as an initial treatment. Forty-five patients had nasal NTCL, whereas 14 had extranasal NTCL. Forty-one patients had stage I/II and 18 had stage III/IV disease. Epstein-Barr virus status was positive in 67.6% of cases. The results of initial chemotherapy were complete remission in 35.6% of the patients, 2-year disease-free survival in 22.9% and 2-year overall survival in 44.2%. Adjuvant radiotherapy after chemotherapy did not improve outcome in stage I/II nasal NTCL. The International Prognostic Index was a significant prognostic factor of complete remission rate, and stage was also significant for disease-free survival.

Therapeutic Outcome of Extranodal NK/T-Cell Lymphoma Initially Treated with Chemotherapy

International Nuclear Information System (INIS)

Kim, Byung Su; Kim, Tae-you; Kim, Chul Woo; Kim, Ji Yeun; Heo, Dae Seog; Bang, Yung-jue; Kim, Noe Kyeong

2003-01-01

The therapeutic outcome of chemotherapy in NK/T cell lymphoma (NTCL) has not been well documented until now. The aims of this study were to investigate the outcome of chemotherapy and to evaluate the clinical factors influencing the responsiveness to chemotherapy. Between 1995 and 2000, 59 patients received anthracycline-based chemotherapy as an initial treatment. Forty-five patients had nasal NTCL, whereas 14 had extranasal NTCL. Forty-one patients had stage I/II and 18 had stage III/IV disease. Epstein-Barr virus status was positive in 67.6% of cases. The results of initial chemotherapy were complete remission in 35.6% of the patients, 2-year disease-free survival in 22.9% and 2-year overall survival in 44.2%. Adjuvant radiotherapy after chemotherapy did not improve outcome in stage I/II nasal NTCL. The International Prognostic Index was a significant prognostic factor of complete remission rate, and stage was also significant for disease-free survival

Investigating potential exogenous tumor initiating and promoting factors for Cutaneous T-Cell Lymphomas (CTCL), a rare skin malignancy

DEFF Research Database (Denmark)

Litvinov, Ivan V.; Shtreis, Anna; Kobayashi, Kenneth

2016-01-01

-Cell lymphotropic virus type 1 (HTLV1), Epstein-Barr virus (EBV), and herpes simplex virus (HSV). In this report, we review recent evidence evaluating the involvement of these agents in cancer initiation/progression. Most importantly, recent molecular experimental evidence documented for the first time that S....... aureus can activate oncogenic STAT3 signaling in malignant T cells. Specifically, S. aureus Enterotoxin type A (SEA) was recently shown to trigger non-malignant infiltrating T cells to release IL-2 and other cytokines. These signals upon binging to their cognate receptors on malignant T cells...

R-loops and initiation of DNA replication in human cells: a missing link?

Directory of Open Access Journals (Sweden)

Rodrigo eLombraña

2015-04-01

Full Text Available The unanticipated widespread occurrence of stable hybrid DNA/RNA structures (R-loops in human cells and the increasing evidence of their involvement in several human malignancies have invigorated the research on R-loop biology in recent years. Here we propose that physiological R-loop formation at CpG island promoters can contribute to DNA replication origin specification at these regions, the most efficient replication initiation sites in mammalian cells. Quite likely, this occurs by the strand-displacement reaction activating the formation of G-quadruplex structures that target the Origin Recognition Complex (ORC in the single-stranded conformation. In agreement with this, we found that R-loops co-localize with the ORC within the same CpG island region in a significant fraction of these efficient replication origins, precisely at the position displaying the highest density of G4 motifs. This scenario builds on the connection between transcription and replication in human cells and suggests that R-loop dysregulation at CpG island promoter-origins might contribute to the phenotype of DNA replication abnormalities and loss of genome integrity detected in cancer cells.

Lipid raft regulates the initial spreading of melanoma A375 cells by modulating β1 integrin clustering.

Science.gov (United States)

Wang, Ruifei; Bi, Jiajia; Ampah, Khamal Kwesi; Zhang, Chunmei; Li, Ziyi; Jiao, Yang; Wang, Xiaoru; Ba, Xueqing; Zeng, Xianlu

2013-08-01

Cell adhesion and spreading require integrins-mediated cell-extracellular matrix interaction. Integrins function through binding to extracellular matrix and subsequent clustering to initiate focal adhesion formation and actin cytoskeleton rearrangement. Lipid raft, a liquid ordered plasma membrane microdomain, has been reported to play major roles in membrane motility by regulating cell surface receptor function. Here, we identified that lipid raft integrity was required for β1 integrin-mediated initial spreading of melanoma A375 cells on fibronectin. We found that lipid raft disruption with methyl-β-cyclodextrin led to the inability of focal adhesion formation and actin cytoskeleton rearrangement by preventing β1 integrin clustering. Furthermore, we explored the possible mechanism by which lipid raft regulates β1 integrin clustering and demonstrated that intact lipid raft could recruit and modify some adaptor proteins, such as talin, α-actinin, vinculin, paxillin and FAK. Lipid raft could regulate the location of these proteins in lipid raft fractions and facilitate their binding to β1 integrin, which may be crucial for β1 integrin clustering. We also showed that lipid raft disruption impaired A375 cell migration in both transwell and wound healing models. Together, these findings provide a new insight for the relationship between lipid raft and the regulation of integrins. Copyright © 2013 Elsevier Ltd. All rights reserved.

Single-unit-cell layer established Bi 2 WO 6 3D hierarchical architectures: Efficient adsorption, photocatalysis and dye-sensitized photoelectrochemical performance

Energy Technology Data Exchange (ETDEWEB)

Huang, Hongwei; Cao, Ranran; Yu, Shixin; Xu, Kang; Hao, Weichang; Wang, Yonggang; Dong, Fan; Zhang, Tierui; Zhang, Yihe

2017-12-01

Single-layer catalysis sparks huge interests and gains widespread attention owing to its high activity. Simultaneously, three-dimensional (3D) hierarchical structure can afford large surface area and abundant reactive sites, contributing to high efficiency. Herein, we report an absorbing single-unit-cell layer established Bi2WO6 3D hierarchical architecture fabricated by a sodium dodecyl benzene sulfonate (SDBS)-assisted assembled strategy. The DBS- long chains can adsorb on the (Bi2O2)2+ layers and hence impede stacking of the layers, resulting in the single-unit-cell layer. We also uncovered that SDS with a shorter chain is less effective than SDBS. Due to the sufficient exposure of surface O atoms, single-unit-cell layer 3D Bi2WO6 shows strong selectivity for adsorption on multiform organic dyes with different charges. Remarkably, the single-unit-cell layer 3D Bi2WO6 casts profoundly enhanced photodegradation activity and especially a superior photocatalytic H2 evolution rate, which is 14-fold increase in contrast to the bulk Bi2WO6. Systematic photoelectrochemical characterizations disclose that the substantially elevated carrier density and charge separation efficiency take responsibility for the strengthened photocatalytic performance. Additionally, the possibility of single-unit-cell layer 3D Bi2WO6 as dye-sensitized solar cells (DSSC) has also been attempted and it was manifested to be a promising dye-sensitized photoanode for oxygen evolution reaction (ORR). Our work not only furnish an insight into designing single-layer assembled 3D hierarchical architecture, but also offer a multi-functional material for environmental and energy applications.

The cancer cell map initiative: defining the hallmark networks of cancer.

Science.gov (United States)

Krogan, Nevan J; Lippman, Scott; Agard, David A; Ashworth, Alan; Ideker, Trey

2015-05-21

Progress in DNA sequencing has revealed the startling complexity of cancer genomes, which typically carry thousands of somatic mutations. However, it remains unclear which are the key driver mutations or dependencies in a given cancer and how these influence pathogenesis and response to therapy. Although tumors of similar types and clinical outcomes can have patterns of mutations that are strikingly different, it is becoming apparent that these mutations recurrently hijack the same hallmark molecular pathways and networks. For this reason, it is likely that successful interpretation of cancer genomes will require comprehensive knowledge of the molecular networks under selective pressure in oncogenesis. Here we announce the creation of a new effort, The Cancer Cell Map Initiative (CCMI), aimed at systematically detailing these complex interactions among cancer genes and how they differ between diseased and healthy states. We discuss recent progress that enables creation of these cancer cell maps across a range of tumor types and how they can be used to target networks disrupted in individual patients, significantly accelerating the development of precision medicine. Copyright © 2015 Elsevier Inc. All rights reserved.

Plant cell culture initiation

NARCIS (Netherlands)

Hall, R.D.

2000-01-01

The use of cultured plant cells in either organized or unorganized form has increased vey considerably in the last 10-15 yr. Many new technologies have been developed and applications in both fundamental and applied research have led to the development of some powerful tools for improving our

The Daniell cell, Ohm's law, and the emergence of the International System of Units

Science.gov (United States)

Jayson, Joel S.

2014-01-01

Telegraphy originated in the 1830s and 40 s and flourished in the following decades but with a patchwork of electrical standards. Electromotive force was for the most part measured in units of the predominant Daniell cell, but each telegraphy company had their own resistance standard. In 1862, the British Association for the Advancement of Science formed a committee to address this situation. By 1873, they had given definition to the electromagnetic system of units (emu) and defined the practical units of the ohm as 109 emu units of resistance and the volt as 108 emu units of electromotive force. These recommendations were ratified and expanded upon in a series of international congresses held between 1881 and 1904. A proposal by Giovanni Giorgi in 1901 took advantage of a coincidence between the conversion of the units of energy in the emu system (the erg) and in the practical system (the Joule). As it was, the same conversion factor existed between the cgs based emu system and a theretofore undefined MKS system. By introducing another unit X (where X could be any of the practical electrical units), Giorgi demonstrated that a self-consistent MKSX system was tenable without the need for multiplying factors. Ultimately, the ampere was selected as the fourth unit. It took nearly 60 years, but in 1960, Giorgi's proposal was incorporated as the core of the newly inaugurated International System of Units (SI). This article surveys the physics, physicists, and events that contributed to those developments.

The lipid fraction of human milk initiates adipocyte differentiation in 3T3-L1 cells.

Science.gov (United States)

Fujisawa, Yasuko; Yamaguchi, Rie; Nagata, Eiko; Satake, Eiichiro; Sano, Shinichiro; Matsushita, Rie; Kitsuta, Kazunobu; Nakashima, Shinichi; Nakanishi, Toshiki; Nakagawa, Yuichi; Ogata, Tsutomu

2013-09-01

The prevalence of childhood obesity has increased worldwide over the past decade. Despite evidence that human milk lowers the risk of childhood obesity, the mechanism is not fully understood. We investigated the direct effect of human milk on differentiation of 3T3-L1 preadipocytes. 3T3-L1 preadipocytes were treated with donated human milk only or the combination of the standard hormone mixture; insulin, dexamethasone (DEX), and 3-isobututyl-1-methylxanthine (IBMX). Furthermore, the induction of preadipocyte differentiation by extracted lipids from human milk was tested in comparison to the cells treated with lipid extracts from infant formula. Adipocyte differentiation, specific genes as well as formation of lipid droplets were examined. We clearly show that lipids present in human milk initiate 3T3-L1 preadipocyte differentiation. In contrast, this effect was not observed in response to lipids present in infant formula. The initiation of preadipocyte differentiation by human milk was enhanced by adding the adipogenic hormone, DEX or insulin. The expression of late adipocyte markers in Day 7 adipocytes that have been induced into differentiation with human milk lipid extracts was comparable to those in control cells initiated by a standard adipogenic hormone cocktail. These results demonstrate that human milk contains bioactive lipids that can initiate preadipocyte differentiation in the absence of the standard adipogenic compounds via a unique pathway. Copyright © 2013 Elsevier Ltd. All rights reserved.

Is sphere assay useful for the identification of cancer initiating cells of the ovary?

Science.gov (United States)

Martínez-Serrano, María José; Caballero-Baños, Miguel; Vilella, Ramon; Vidal, Laura; Pahisa, Jaume; Martínez-Roman, Sergio

2015-01-01

Current evidence suggests that the presence of tumor-initiating cells (TICs) in epithelial ovarian cancer (EOC) has a role in chemoresistance and relapse. Surface markers such as CD44(+)/CD24(-), CD117(+), and CD133(+) expression have been reported as potential markers for TICs related to ovarian cancer and tumorigenic cell lines. In this study, we have investigated if spheroid forms are TIC specific or whether they can also be produced by somatic stem cells from healthy tissue in vitro. In addition, we also investigated the specificity of surface markers to identify TICs from papillary serous EOC patients. Cells were obtained from fresh tumors from 10 chemotherapy-naive patients with EOC, and cells from ovarian and tubal epithelium were obtained from 5 healthy menopausal women undergoing surgery for benign pathology and cultured in standard and in selective medium. Cells forming nonadherent spheroids were considered TICs, and the adherent cells were considered as non-TIC-like. Percentages of CD24(+), CD44(+), CD117(+), CD133(+), and vascular endothelial growth factor receptor (VEGF-R)(+) cell surface markers were analyzed by flow cytometry. Four of 10 EOC cell tissues were excluded from the study. Tumor cells cultured in selective medium developed spheroid forms after 1 to 7 weeks in 5 of 6 EOC patients. No spheroid forms were observed in cultures of cells from healthy women. Unlike previously published data, low levels of CD24(+), CD44(+), CD117(+), and VEGF-R(+) expression were observed in spheroid cells, whereas expression of CD133(+) was moderate but higher in adherent cells from papillary serous EOC cells in comparison with adherent cells from controls. Papillary serous EOC contains TICs that form spheroids with low expression of CD44(+), CD24(+), CD117(+) and VEGF-R(+). Further research is required to find specific surface markers to identify papillary serous TICs.

30 CFR 56.6501 - Nonelectric initiation systems.

Science.gov (United States)

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Nonelectric initiation systems. 56.6501 Section... Nonelectric Blasting § 56.6501 Nonelectric initiation systems. (a) When the nonelectric initiation system uses... for uninterrupted propagation; (2) Factory-made units shall be used as assembled and shall not be cut...

Determination of the bonding strength in solid oxide fuel cells' interfaces by Schwickerath crack initiation test

DEFF Research Database (Denmark)

Boccaccini, D. N.; Sevecek, O.; Frandsen, Henrik Lund

2017-01-01

An adaptation of the Schwickerath crack initiation test (ISO 9693) was used to determine the bonding strength between an anode support and three different cathodes with a solid oxide fuel cell interconnect. Interfacial elemental characterization of the interfaces was carried out by SEM/EDS analys...

Mixed-Initiative Control of Autonomous Unmanned Units Under Uncertainty

National Research Council Canada - National Science Library

Thrun, Sebvastian; Gordon, Geoffrey; Burstein, Mark; Diller, David; Fox, Dieter

2006-01-01

.... We developed this control model using Partially Observable Markov Decision Processes. The mixed-initiative interactions enabled users to describe constraints at multiple levels of the planning hierarchy...

Targeting cytokine signaling checkpoint CIS activates NK cells to protect from tumor initiation and metastasis

Science.gov (United States)

Putz, Eva M.; Guillerey, Camille; Kos, Kevin; Stannard, Kimberley; Miles, Kim; Delconte, Rebecca B.; Nicholson, Sandra E.; Huntington, Nicholas D.; Smyth, Mark J.

2017-01-01

ABSTRACT The cytokine-induced SH2-containing protein CIS belongs to the suppressor of cytokine signaling (SOCS) protein family. Here, we show the critical role of CIS in suppressing natural killer (NK) cell control of tumor initiation and metastasis. Cish-deficient mice were highly resistant to methylcholanthrene-induced sarcoma formation and protected from lung metastasis of B16F10 melanoma and RM-1 prostate carcinoma cells. In contrast, the growth of primary subcutaneous tumors, including those expressing the foreign antigen OVA, was unchanged in Cish-deficient mice. The combination of Cish deficiency and relevant targeted and immuno-therapies such as combined BRAF and MEK inhibitors, immune checkpoint blockade antibodies, IL-2 and type I interferon revealed further improved control of metastasis. The data clearly indicate that targeting CIS promotes NK cell antitumor functions and CIS holds great promise as a novel target in NK cell immunotherapy. PMID:28344878

Fuel Cell Demonstration Program

Energy Technology Data Exchange (ETDEWEB)

Gerald Brun

2006-09-15

In an effort to promote clean energy projects and aid in the commercialization of new fuel cell technologies the Long Island Power Authority (LIPA) initiated a Fuel Cell Demonstration Program in 1999 with six month deployments of Proton Exchange Membrane (PEM) non-commercial Beta model systems at partnering sites throughout Long Island. These projects facilitated significant developments in the technology, providing operating experience that allowed the manufacturer to produce fuel cells that were half the size of the Beta units and suitable for outdoor installations. In 2001, LIPA embarked on a large-scale effort to identify and develop measures that could improve the reliability and performance of future fuel cell technologies for electric utility applications and the concept to establish a fuel cell farm (Farm) of 75 units was developed. By the end of October of 2001, 75 Lorax 2.0 fuel cells had been installed at the West Babylon substation on Long Island, making it the first fuel cell demonstration of its kind and size anywhere in the world at the time. Designed to help LIPA study the feasibility of using fuel cells to operate in parallel with LIPA's electric grid system, the Farm operated 120 fuel cells over its lifetime of over 3 years including 3 generations of Plug Power fuel cells (Lorax 2.0, Lorax 3.0, Lorax 4.5). Of these 120 fuel cells, 20 Lorax 3.0 units operated under this Award from June 2002 to September 2004. In parallel with the operation of the Farm, LIPA recruited government and commercial/industrial customers to demonstrate fuel cells as on-site distributed generation. From December 2002 to February 2005, 17 fuel cells were tested and monitored at various customer sites throughout Long Island. The 37 fuel cells operated under this Award produced a total of 712,635 kWh. As fuel cell technology became more mature, performance improvements included a 1% increase in system efficiency. Including equipment, design, fuel, maintenance

DNA Amplification by Breakage/Fusion/Bridge Cycles Initiated by Spontaneous Telomere Loss in a Human Cancer Cell Line

Directory of Open Access Journals (Sweden)

Anthony W.l. Lo

2002-01-01

Full Text Available The development of genomic instability is an important step in generatingthe multiple genetic changes required for cancer. One consequence of genomic instability is the overexpression of oncogenes due to gene amplification. One mechanism for gene amplification is the breakagelfusionlbridge (B/F/Bcyclethatinvolvesthe repeated fusion and breakage of chromosomes following the loss of a telomere. B/F/B cycles have been associated with low-copy gene amplification in human cancer cells, and have been proposed to be an initiating event in high-copy gene amplification. We have found that spontaneous telomere loss on a marker chromosome 16 in a human tumor cell line results in sister chromatid fusion and prolonged periods of chromosome instability. The high rate of anaphase bridges involving chromosome 16 demonstrates that this instability results from B/F/B cycles. The amplification of subtelomeric DNA on the marker chromosome provides conclusive evidence that B/F/B cycles initiated by spontaneous telomere loss are a mechanism for gene amplification in human cancer cells.

Use of an adaptable cell culture kit for performing lymphocyte and monocyte cell cultures in microgravity

Science.gov (United States)

Hatton, J. P.; Lewis, M. L.; Roquefeuil, S. B.; Chaput, D.; Cazenave, J. P.; Schmitt, D. A.

1998-01-01

The results of experiments performed in recent years on board facilities such as the Space Shuttle/Spacelab have demonstrated that many cell systems, ranging from simple bacteria to mammalian cells, are sensitive to the microgravity environment, suggesting gravity affects fundamental cellular processes. However, performing well-controlled experiments aboard spacecraft offers unique challenges to the cell biologist. Although systems such as the European 'Biorack' provide generic experiment facilities including an incubator, on-board 1-g reference centrifuge, and contained area for manipulations, the experimenter must still establish a system for performing cell culture experiments that is compatible with the constraints of spaceflight. Two different cell culture kits developed by the French Space Agency, CNES, were recently used to perform a series of experiments during four flights of the 'Biorack' facility aboard the Space Shuttle. The first unit, Generic Cell Activation Kit 1 (GCAK-1), contains six separate culture units per cassette, each consisting of a culture chamber, activator chamber, filtration system (permitting separation of cells from supernatant in-flight), injection port, and supernatant collection chamber. The second unit (GCAK-2) also contains six separate culture units, including a culture, activator, and fixation chambers. Both hardware units permit relatively complex cell culture manipulations without extensive use of spacecraft resources (crew time, volume, mass, power), or the need for excessive safety measures. Possible operations include stimulation of cultures with activators, separation of cells from supernatant, fixation/lysis, manipulation of radiolabelled reagents, and medium exchange. Investigations performed aboard the Space Shuttle in six different experiments used Jurkat, purified T-cells or U937 cells, the results of which are reported separately. We report here the behaviour of Jurkat and U937 cells in the GCAK hardware in ground

Sector activities and lessons learned around initial implementation of the United States national physical activity plan.

Science.gov (United States)

Evenson, Kelly R; Satinsky, Sara B

2014-08-01

National plans are increasingly common but infrequently evaluated. The 2010 United States National Physical Activity Plan (NPAP) provided strategies to increase population levels of physical activity. This paper describes (i) the initial accomplishments of the NPAP sector teams, and (ii) results from a process evaluation to determine how the sectors operated, their cross-sector collaboration, challenges encountered, and positive experiences. During 2011, a quarterly reporting system was developed to capture sector-level activities. A year-end interview derived more detailed information. Interviews with 12 sector leads were recorded, transcribed verbatim, and analyzed for common themes. The 6 sectors worked on goals from the implementation plan that focused broadly on education, promotion, intervention, policy, collaboration, and evaluation. Through year-end interviews, themes were generated around operations, goal setting, and cross-sector collaboration. Challenges to the NPAP work included lack of funding and time, the need for marketing and promotion, and organizational support. Positive experiences included collaboration, efficiency of work, enhanced community dynamic, and accomplishments toward NPAP goals. These initial results on the NPAP sector teams can be used as a baseline assessment for future monitoring. The lessons learned may be useful to other practitioners developing evaluations around state- or national-level plans.

Chemo-radionuclide therapy for thyroid cancer. Initial experimental study with cultured cells

International Nuclear Information System (INIS)

Misaki, Takashi; Iwata, Masahiro; Iida, Yasuhiro; Kasagi, Kanji; Konishi, Junji

2002-01-01

Radioiodine therapy has long been used for distant metastases of thyroid cancer. Although partially effective in most cases, it can render a complete cure only in a limited number of patients. One way to enhance its efficacy would be to combine it with antineoplastic agents. Here we describe an initial in vitro evaluation with 4 thyroid cancer cell lines. Cells were sparsely seeded in microtiter plates and allowed to grow for 2 days; then they were exposed to sublethal concentrations of cisplatin (CDDP), doxorubicin (Dox), or 5-fluorouracil (5-FU), followed by treatment with I-131 for 48 hr. Cell survival was measured with a commercial kit based on the colorimetry of succinate dehydrogenase activity. Chemotherapeutic drugs exerted similar concentration-dependent cytotoxic effects in all 4 cell lines. The doses necessary to reduce the surviving fraction to half of the control were about 3 μg/ml for CDDP, 0.3 μg/ml for Dox, and 3 μg/ml for 5-FU (when used continuously for 48 hours). On the other hand, sensitivity to I-131 irradiation differed among the lines; same doses (7.4-14.8 MBq/ml) caused the greatest damage in FRO cells, a modest effect in NPA and WRO, and only minimal change in B-CPAP. The combined effect was most demonstrable in wells treated with Dox and radioiodine, whereas the addition of CDDP or 5-FU had marginal or insignificant merit, respectively. In FRO cells, half-lethal doses of the above mentioned CDDP, Dox, and 5-FU, when used together with 14.8 MBq/ml I-131, reduced cell survival to 54.5%, 29.4% and 33.4%, respectively, vs. 60.2% with radioiodine alone. In vitro, clinical concentrations of Dox can accelerate the killing of thyroid cancer cells by radioiodine. These favorable experimental results warrant future studies to evaluate whether this new bidisciplinary approach is clinically relevant and feasible. (author)

Chemo-radionuclide therapy for thyroid cancer. Initial experimental study with cultured cells

Energy Technology Data Exchange (ETDEWEB)

Misaki, Takashi; Iwata, Masahiro; Iida, Yasuhiro; Kasagi, Kanji; Konishi, Junji [Kyoto Univ. (Japan). Graduate School of Medicine

2002-09-01

Radioiodine therapy has long been used for distant metastases of thyroid cancer. Although partially effective in most cases, it can render a complete cure only in a limited number of patients. One way to enhance its efficacy would be to combine it with antineoplastic agents. Here we describe an initial in vitro evaluation with 4 thyroid cancer cell lines. Cells were sparsely seeded in microtiter plates and allowed to grow for 2 days; then they were exposed to sublethal concentrations of cisplatin (CDDP), doxorubicin (Dox), or 5-fluorouracil (5-FU), followed by treatment with I-131 for 48 hr. Cell survival was measured with a commercial kit based on the colorimetry of succinate dehydrogenase activity. Chemotherapeutic drugs exerted similar concentration-dependent cytotoxic effects in all 4 cell lines. The doses necessary to reduce the surviving fraction to half of the control were about 3 {mu}g/ml for CDDP, 0.3 {mu}g/ml for Dox, and 3 {mu}g/ml for 5-FU (when used continuously for 48 hours). On the other hand, sensitivity to I-131 irradiation differed among the lines; same doses (7.4-14.8 MBq/ml) caused the greatest damage in FRO cells, a modest effect in NPA and WRO, and only minimal change in B-CPAP. The combined effect was most demonstrable in wells treated with Dox and radioiodine, whereas the addition of CDDP or 5-FU had marginal or insignificant merit, respectively. In FRO cells, half-lethal doses of the above mentioned CDDP, Dox, and 5-FU, when used together with 14.8 MBq/ml I-131, reduced cell survival to 54.5%, 29.4% and 33.4%, respectively, vs. 60.2% with radioiodine alone. In vitro, clinical concentrations of Dox can accelerate the killing of thyroid cancer cells by radioiodine. These favorable experimental results warrant future studies to evaluate whether this new bidisciplinary approach is clinically relevant and feasible. (author)

48 CFR 25.405 - Caribbean Basin Trade Initiative.

Science.gov (United States)

2010-10-01

... Initiative. 25.405 Section 25.405 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION SOCIOECONOMIC PROGRAMS FOREIGN ACQUISITION Trade Agreements 25.405 Caribbean Basin Trade Initiative. Under the Caribbean Basin Trade Initiative, the United States Trade Representative has determined that, for...

Compact Design of 10 kW Proton Exchange Membrane Fuel Cell Stack Systems with Microcontroller Units

Directory of Open Access Journals (Sweden)

Hsiaokang Ma

2014-04-01

Full Text Available In this study, fuel, oxidant supply and cooling systems with microcontroller units (MCU are developed in a compact design to fit two 5 kW proton exchange membrane fuel cell (PEMFC stacks. At the initial stage, the testing facility of the system has a large volume (2.0 m × 2.0 m × 1.5 m with a longer pipeline and excessive control sensors for safe testing. After recognizing the performance and stability of stack, the system is redesigned to fit in a limited space (0.4 m × 0.5 m × 0.8 m. Furthermore, the stack performance is studied under different hydrogen recycling modes. Then, two similar 5 kW stacks are directly coupled with diodes to obtain a higher power output and safe operation. The result shows that the efficiency of the 5 kW stack is 43.46% with a purge period of 2 min with hydrogen recycling and that the hydrogen utilization rate µf is 66.31%. In addition, the maximum power output of the twin-coupled module (a power module with two stacks in electrical cascade/parallel arrangement is 9.52 kW.

The two chromosomes of Vibrio cholerae are initiated at different time points in the cell cycle

DEFF Research Database (Denmark)

Rasmussen, Tue; Jensen, Rasmus Bugge; Skovgaard, Ole

2007-01-01

for analysing flow cytometry data and marker frequency analysis, we show that the small chromosome II is replicated late in the C period of the cell cycle, where most of chromosome I has been replicated. Owing to the delay in initiation of chromosome II, the two chromosomes terminate replication...... at approximately the same time and the average number of replication origins per cell is higher for chromosome I than for chromosome II. Analysis of cell-cycle parameters shows that chromosome replication and segregation is exceptionally fast in V. cholerae. The divided genome and delayed replication of chromosome...... II may reduce the metabolic burden and complexity of chromosome replication by postponing DNA synthesis to the last part of the cell cycle and reducing the need for overlapping replication cycles during rapid proliferation...

Neurotrophin Signaling via TrkB and TrkC Receptors Promotes the Growth of Brain Tumor-initiating Cells*

Science.gov (United States)

Lawn, Samuel; Krishna, Niveditha; Pisklakova, Alexandra; Qu, Xiaotao; Fenstermacher, David A.; Fournier, Michelle; Vrionis, Frank D.; Tran, Nam; Chan, Jennifer A.; Kenchappa, Rajappa S.; Forsyth, Peter A.

2015-01-01

Neurotrophins and their receptors are frequently expressed in malignant gliomas, yet their functions are largely unknown. Previously, we have shown that p75 neurotrophin receptor is required for glioma invasion and proliferation. However, the role of Trk receptors has not been examined. In this study, we investigated the importance of TrkB and TrkC in survival of brain tumor-initiating cells (BTICs). Here, we show that human malignant glioma tissues and also tumor-initiating cells isolated from fresh human malignant gliomas express the neurotrophin receptors TrkB and TrkC, not TrkA, and they also express neurotrophins NGF, BDNF, and neurotrophin 3 (NT3). Specific activation of TrkB and TrkC receptors by ligands BDNF and NT3 enhances tumor-initiating cell viability through activation of ERK and Akt pathways. Conversely, TrkB and TrkC knockdown or pharmacologic inhibition of Trk signaling decreases neurotrophin-dependent ERK activation and BTIC growth. Further, pharmacological inhibition of both ERK and Akt pathways blocked BDNF, and NT3 stimulated BTIC survival. Importantly, attenuation of BTIC growth by EGFR inhibitors could be overcome by activation of neurotrophin signaling, and neurotrophin signaling is sufficient for long term BTIC growth as spheres in the absence of EGF and FGF. Our results highlight a novel role for neurotrophin signaling in brain tumor and suggest that Trks could be a target for combinatorial treatment of malignant glioma. PMID:25538243

Neurotrophin signaling via TrkB and TrkC receptors promotes the growth of brain tumor-initiating cells.

Science.gov (United States)

Lawn, Samuel; Krishna, Niveditha; Pisklakova, Alexandra; Qu, Xiaotao; Fenstermacher, David A; Fournier, Michelle; Vrionis, Frank D; Tran, Nam; Chan, Jennifer A; Kenchappa, Rajappa S; Forsyth, Peter A

2015-02-06

Neurotrophins and their receptors are frequently expressed in malignant gliomas, yet their functions are largely unknown. Previously, we have shown that p75 neurotrophin receptor is required for glioma invasion and proliferation. However, the role of Trk receptors has not been examined. In this study, we investigated the importance of TrkB and TrkC in survival of brain tumor-initiating cells (BTICs). Here, we show that human malignant glioma tissues and also tumor-initiating cells isolated from fresh human malignant gliomas express the neurotrophin receptors TrkB and TrkC, not TrkA, and they also express neurotrophins NGF, BDNF, and neurotrophin 3 (NT3). Specific activation of TrkB and TrkC receptors by ligands BDNF and NT3 enhances tumor-initiating cell viability through activation of ERK and Akt pathways. Conversely, TrkB and TrkC knockdown or pharmacologic inhibition of Trk signaling decreases neurotrophin-dependent ERK activation and BTIC growth. Further, pharmacological inhibition of both ERK and Akt pathways blocked BDNF, and NT3 stimulated BTIC survival. Importantly, attenuation of BTIC growth by EGFR inhibitors could be overcome by activation of neurotrophin signaling, and neurotrophin signaling is sufficient for long term BTIC growth as spheres in the absence of EGF and FGF. Our results highlight a novel role for neurotrophin signaling in brain tumor and suggest that Trks could be a target for combinatorial treatment of malignant glioma. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Treatment of initially metastatic small-cell lung cancer

International Nuclear Information System (INIS)

Kohutek, F.; Bystricky, B.; Tamasova, M.

2013-01-01

Lung cancer (LC) is the most common cause of death associated with neoplasms. The incidence of LC in 2007 was 71.3/100,000 men and 18.6/100,000 women in Slovakia. Small-cell lung cancer (SCLC) includes 15 - 18% of all cases. The diagnosis of LC is based on patient's history, physical examination, basic laboratory tests, x-ray imaging and computed tomography (CT) imaging and histology. The material required for histology can be obtained by means of endoscopy or surgery. Ultrasonography (USG) and/or CT of abdomen is commonly performed as a part of staging process, along with CT or MRI of brain. Bone scan is performed in case of suspicion of bone involvement. According to TNM classification, seventh edition, the same classification can be used for SCLC and non-small cell lung cancer (NSCLC). Chemotherapy and radiotherapy are available for treatment of initially metastatic SCLC. First-line chemotherapy regimen should be based on combination of cisplatin or carboplatin with etoposide (PE). Alternatively, CAV regimen (cyclophosphamide, doxorubicin, vincristine) can be used. Newer regimens did not provide benefit when compared to standard regimens. If progression occurs later than 3 months after finishing first-line chemotherapy, the same regimen may be used in second-line chemotherapy. If progression occurs earlier than 3 months after finishing first-line chemotherapy, topotecan-based regimen is an option for second-line line chemotherapy. Despite promising outcomes of amrubicin-based second-line chemotherapy in Japan, amrubicin is not available in countries of E U. Standard therapy schedules do not include radiotherapy targeted on primary tumor and affected lymph-nodes. According to American and European guidelines, prophylactic cranial irradiation is recommended for patients with extensive disease-SCLC with good performance status after achieving complete or partial response to first-line chemotherapy. (author)

Breast abscess as the initial manifestation of primary pure squamous cell carcinoma: a rare presentation and literature review.

Science.gov (United States)

Salemis, Nikolaos S

2011-01-01

Primary squamous cell carcinoma of the breast is a very rare tumor accounting for less than 0.4% of all breast cancers. Fewer than 100 cases have been reported in the literature so far. The diagnosis requires strict pathologic criteria to be fulfilled. Due to the rarity of this tumor the optimal treatment and prognosis are both unclear. Breast abscess as the initial presentation of a primary squamous cell breast carcinoma is an extremely rare clinical entity. In this study, we describe a case of a 61-year-old postmenopausal woman who presented with typical manifestations of a breast abscess and was diagnosed with a pure primary squamous cell breast carcinoma. Diagnostic evaluation and management of the patient are discussed along with a review of the literature. Despite its rarity, the possibility of a primary pure squamous cell breast carcinoma should always be considered in the differential diagnosis in postmenopausal patients presenting with manifestations of a breast abscess, especially in those who respond poorly to the initial treatment. Physicians should be aware of this rare malignancy in order to avoid delays in diagnosis and treatment.

Primary Hepatosplenic B-cell Lymphoma: Initial Diagnosis and Assessment of Therapeutic Response with F-18 FDG PET/CT

International Nuclear Information System (INIS)

Kang, Sung Min; Lee, Hong Je; Seo, Ji Hyoung; Lee, Sang Woo; Ahn, Byeong Cheol; Lee, Jae Tae

2008-01-01

A 52-year-old woman with a history of general weakness, fatigue, weight loss, elevated serum levels of liver transaminase enzyme for three months underwent an F-18 FDG PET/CT to evaluate a cause of the hepatosplenomegaly found on abdominal ultrasonography. Initial PET/CT revealed markedly enlarged liver and spleen with intense FDG uptake. Otherwise, there were no areas of abnormal FDG uptake in whole body image. Histological evaluation by a hepatic needle biopsy demonstrated diffuse large B cell type lymphoma and final diagnosis for this patient was hepatosplenic B-cell lymphoma. She received five cycles of CHOP chemotherapy, and second PET/CT was followed after then. Follow-up PET-CT revealed normal sized liver with disappearance of abnormal FDG uptake. Hepatosplenic B-cell lymphoma is relatively rare and mostly presents as single or multiple nodules. Diffuse type hepatosplenic lymphoma is extremely rare and poorly recognized entity. The diagnosis is very difficult and complicated by the presence of misleading symptoms.4 In this rare hepatosplenic B-cell lymphoma case, F-18 FDG PET/CT provided a initial diagnostic clue of hepatosplenic lymphoma and an accurate chemotherapy response

Primary Hepatosplenic B-cell Lymphoma: Initial Diagnosis and Assessment of Therapeutic Response with F-18 FDG PET/CT

Energy Technology Data Exchange (ETDEWEB)

Kang, Sung Min; Lee, Hong Je; Seo, Ji Hyoung; Lee, Sang Woo; Ahn, Byeong Cheol; Lee, Jae Tae [Kyungpook National University Hospital, Daegu (Korea, Republic of)

2008-08-15

A 52-year-old woman with a history of general weakness, fatigue, weight loss, elevated serum levels of liver transaminase enzyme for three months underwent an F-18 FDG PET/CT to evaluate a cause of the hepatosplenomegaly found on abdominal ultrasonography. Initial PET/CT revealed markedly enlarged liver and spleen with intense FDG uptake. Otherwise, there were no areas of abnormal FDG uptake in whole body image. Histological evaluation by a hepatic needle biopsy demonstrated diffuse large B cell type lymphoma and final diagnosis for this patient was hepatosplenic B-cell lymphoma. She received five cycles of CHOP chemotherapy, and second PET/CT was followed after then. Follow-up PET-CT revealed normal sized liver with disappearance of abnormal FDG uptake. Hepatosplenic B-cell lymphoma is relatively rare and mostly presents as single or multiple nodules. Diffuse type hepatosplenic lymphoma is extremely rare and poorly recognized entity. The diagnosis is very difficult and complicated by the presence of misleading symptoms.4 In this rare hepatosplenic B-cell lymphoma case, F-18 FDG PET/CT provided a initial diagnostic clue of hepatosplenic lymphoma and an accurate chemotherapy response.

Autoimmune Th17 Cells Induced Synovial Stromal and Innate Lymphoid Cell Secretion of the Cytokine GM-CSF to Initiate and Augment Autoimmune Arthritis.

Science.gov (United States)

Hirota, Keiji; Hashimoto, Motomu; Ito, Yoshinaga; Matsuura, Mayumi; Ito, Hiromu; Tanaka, Masao; Watanabe, Hitomi; Kondoh, Gen; Tanaka, Atsushi; Yasuda, Keiko; Kopf, Manfred; Potocnik, Alexandre J; Stockinger, Brigitta; Sakaguchi, Noriko; Sakaguchi, Shimon

2018-06-19

Despite the importance of Th17 cells in autoimmune diseases, it remains unclear how they control other inflammatory cells in autoimmune tissue damage. Using a model of spontaneous autoimmune arthritis, we showed that arthritogenic Th17 cells stimulated fibroblast-like synoviocytes via interleukin-17 (IL-17) to secrete the cytokine GM-CSF and also expanded synovial-resident innate lymphoid cells (ILCs) in inflamed joints. Activated synovial ILCs, which expressed CD25, IL-33Ra, and TLR9, produced abundant GM-CSF upon stimulation by IL-2, IL-33, or CpG DNA. Loss of GM-CSF production by either ILCs or radio-resistant stromal cells prevented Th17 cell-mediated arthritis. GM-CSF production by Th17 cells augmented chronic inflammation but was dispensable for the initiation of arthritis. We showed that GM-CSF-producing ILCs were present in inflamed joints of rheumatoid arthritis patients. Thus, a cellular cascade of autoimmune Th17 cells, ILCs, and stromal cells, via IL-17 and GM-CSF, mediates chronic joint inflammation and can be a target for therapeutic intervention. Copyright © 2018 Elsevier Inc. All rights reserved.

Scaffold protein JLP mediates TCR-initiated CD4+T cell activation and CD154 expression.

Science.gov (United States)

Yan, Qi; Yang, Cheng; Fu, Qiang; Chen, Zhaowei; Liu, Shan; Fu, Dou; Rahman, Rahmat N; Nakazato, Ryota; Yoshioka, Katsuji; Kung, Sam K P; Ding, Guohua; Wang, Huiming

2017-07-01

CD4 + T-cell activation and its subsequent induction of CD154 (CD40 ligand, CD40L) expression are pivotal in shaping both the humoral and cellular immune responses. Scaffold protein JLP regulates signal transduction pathways and molecular trafficking inside cells, thus represents a critical component in maintaining cellular functions. Its role in regulating CD4 + T-cell activation and CD154 expression, however, is unclear. Here, we demonstrated expression of JLP in mouse tissues of lymph nodes, thymus, spleen, and also CD4 + T cells. Using CD4+ T cells from jlp-deficient and jlp-wild-type mice, we demonstrated that JLP-deficiency impaired T-cell proliferation, IL-2 production, and CD154 induction upon TCR stimulations, but had no impacts on the expression of other surface molecules such as CD25, CD69, and TCR. These observed impaired T-cell functions in the jlp-/- CD4 + T cells were associated with defective NF-AT activation and Ca 2 + influx, but not the MAPK, NF-κB, as well as AP-1 signaling pathways. Our findings indicated that, for the first time, JLP plays a critical role in regulating CD4 + T cells response to TCR stimulation partly by mediating the activation of TCR-initiated Ca 2+ /NF-AT. Copyright © 2017 Elsevier Ltd. All rights reserved.

Identification of CD34+ and CD34− leukemia-initiating cells in MLL-rearranged human acute lymphoblastic leukemia

Science.gov (United States)

Aoki, Yuki; Watanabe, Takashi; Saito, Yoriko; Kuroki, Yoko; Hijikata, Atsushi; Takagi, Masatoshi; Tomizawa, Daisuke; Eguchi, Mariko; Eguchi-Ishimae, Minenori; Kaneko, Akiko; Ono, Rintaro; Sato, Kaori; Suzuki, Nahoko; Fujiki, Saera; Koh, Katsuyoshi; Ishii, Eiichi; Shultz, Leonard D.; Ohara, Osamu; Mizutani, Shuki

2015-01-01

Translocation of the mixed-lineage leukemia (MLL) gene with AF4, AF9, or ENL results in acute leukemia with both lymphoid and myeloid involvement. We characterized leukemia-initiating cells (LICs) in primary infant MLL-rearranged leukemia using a xenotransplantation model. In MLL-AF4 patients, CD34+CD38+CD19+ and CD34−CD19+ cells initiated leukemia, and in MLL-AF9 patients, CD34−CD19+ cells were LICs. In MLL-ENL patients, either CD34+ or CD34− cells were LICs, depending on the pattern of CD34 expression. In contrast, in patients with these MLL translocations, CD34+CD38−CD19−CD33− cells were enriched for normal hematopoietic stem cells (HSCs) with in vivo long-term multilineage hematopoietic repopulation capacity. Although LICs developed leukemic cells with clonal immunoglobulin heavy-chain (IGH) rearrangement in vivo, CD34+CD38−CD19−CD33− cells repopulated recipient bone marrow and spleen with B cells, showing broad polyclonal IGH rearrangement and recipient thymus with CD4+ single positive (SP), CD8+ SP, and CD4+CD8+ double-positive (DP) T cells. Global gene expression profiling revealed that CD9, CD32, and CD24 were over-represented in MLL-AF4, MLL-AF9, and MLL-ENL LICs compared with normal HSCs. In patient samples, these molecules were expressed in CD34+CD38+ and CD34− LICs but not in CD34+CD38−CD19−CD33− HSCs. Identification of LICs and LIC-specific molecules in primary human MLL-rearranged acute lymphoblastic leukemia may lead to improved therapeutic strategies for MLL-rearranged leukemia. PMID:25538041

Interconnection between the geometry and the structure of unit cells of substances in inorganic chemistry

International Nuclear Information System (INIS)

Eliseev, A.A.; Kuz'micheva, G.M.

1979-01-01

Regularity of interconnection between the geometry and the structure of elementary cells of inorganic compounds is investigated. Structural motives on the basis of NaCl structure for all phases of rare earth chalcogenides are built. It is shown that compounds (phases of variable content), detected on 23 (out of 48 possible) state diagrams of rare earths chalcogen binary systems are closely bound both from the viewpoint of geometric dimensions of elementary cells and structural motives. It is shown that using ion representations the number of formula units in the cell of a new rare earth chalcogenide can be calculated and its structural motif can be built

Chromosomal DNA replication of Vicia faba cells

International Nuclear Information System (INIS)

Ikushima, Takaji

1976-01-01

The chromosomal DNA replication of higher plant cells has been investigated by DNA fiber autoradiography. The nuclear DNA fibers of Vicia root meristematic cells are organized into many tandem arrays of replication units or replicons which exist as clusters with respect to replication. DNA is replicated bidirectionally from the initiation points at the average rate of 0.15 μm/min at 20 0 C, and the average interinitiation interval is about 16 μm. The manner of chromosomal DNA replication in this higher plant is similar to that found in other eukaryotic cells at a subchromosomal level. (auth.)

Canonical and Non-Canonical NF-κB Signaling Promotes Breast Cancer Tumor-Initiating Cells

Science.gov (United States)

Kendellen, Megan F.; Bradford, Jennifer W.; Lawrence, Cortney L.; Clark, Kelly S.; Baldwin, Albert S.

2014-01-01

Tumor-initiating cells (TICs) are a sub-population of cells that exhibit a robust ability to self-renew and contribute to the formation of primary tumors, the relapse of previously treated tumors, and the development of metastases. TICs have been identified in various tumors, including those of the breast, and are particularly enriched in the basal-like and claudin-low subtypes of breast cancer. The signaling pathways that contribute to the function and maintenance of TICs are under intense study. We explored the potential involvement of the NF-κB family of transcription factors in TICs in cell lines that are representative of basal-like and claudin-low breast cancer. NF-κB was found to be activated in breast cancer cells that form tumorspheres efficiently. Moreover, both canonical and non-canonical NF-κB signaling is required for these cells to self-renew in vitro and to form xenograft tumors efficiently in vivo using limiting dilutions of cells. Consistent with this, canonical and non-canonical NF-κB signaling is activated in TICs isolated from breast cancer cell lines. Experimental results indicate that NF-κB promotes the function of TICs by stimulating epithelial-to-mesenchymal transition (EMT) and by upregulating the expression of the inflammatory cytokines IL-1β and IL-6. The results suggest the use of NF-κB inhibitors for clinical therapy of certain breast cancers. PMID:23474754

Digital preservation initiatives in the United States: a summary

OpenAIRE

Marcum, Deanna

2003-01-01

General presentation on how digital preservation issues are being faced in the United States of America. Special reference to the National Digital Information Infrastructure and Preservation Program, that is found at the Library of Congress, and aims to implement a national strategy for the long-term preservation of digital content.

Unexpected exacerbations following initiation of disease-modifying drugs in neuromyelitis optica spectrum disorder: Which factor is responsible, anti-aquaporin 4 antibodies, B cells, Th1 cells, Th2 cells, Th17 cells, or others?

Science.gov (United States)

Kira, Jun-Ichi

2017-08-01

Some disease-modifying drugs for multiple sclerosis, which mainly act on T cells, are ineffective for neuromyelitis optica spectrum disorder and induce unexpected relapses. These include interferon beta, glatiramer acetate, fingolimod, natalizumab, and alemtuzumab. The cases reported here suggest that dimethyl fumarate, which reduces the number of Th1 and Th17 cells and induces IL-4-producing Th2 cells, is also unsuitable for neuromyelitis optica spectrum disorder, irrespective of anti-aquaporin 4 IgG serostatus. Although oral dimethyl fumarate with manageable adverse effects is easy to initiate in the early course of multiple sclerosis, special attention should be paid for atypical demyelinating cases.

Stem-like tumor-initiating cells isolated from IL13Rα2 expressing gliomas are targeted and killed by IL13-zetakine-redirected T Cells.

Science.gov (United States)

Brown, Christine E; Starr, Renate; Aguilar, Brenda; Shami, Andrew F; Martinez, Catalina; D'Apuzzo, Massimo; Barish, Michael E; Forman, Stephen J; Jensen, Michael C

2012-04-15

To evaluate IL13Rα2 as an immunotherapeutic target for eliminating glioma stem-like cancer initiating cells (GSC) of high-grade gliomas, with particular focus on the potential of genetically engineered IL13Rα2-specific primary human CD8(+) CTLs (IL13-zetakine(+) CTL) to target this therapeutically resistant glioma subpopulation. A panel of low-passage GSC tumor sphere (TS) and serum-differentiated glioma lines were expanded from patient glioblastoma specimens. These glioblastoma lines were evaluated for expression of IL13Rα2 and for susceptibility to IL13-zetakine(+) CTL-mediated killing in vitro and in vivo. We observed that although glioma IL13Rα2 expression varies between patients, for IL13Rα2(pos) cases this antigen was detected on both GSCs and more differentiated tumor cell populations. IL13-zetakine(+) CTL were capable of efficient recognition and killing of both IL13Rα2(pos) GSCs and IL13Rα2(pos) differentiated cells in vitro, as well as eliminating glioma-initiating activity in an orthotopic mouse tumor model. Furthermore, intracranial administration of IL13-zetakine(+) CTL displayed robust antitumor activity against established IL13Rα2(pos) GSC TS-initiated orthotopic tumors in mice. Within IL13Rα2 expressing high-grade gliomas, this receptor is expressed by GSCs and differentiated tumor populations, rendering both targetable by IL13-zetakine(+) CTLs. Thus, our results support the potential usefullness of IL13Rα2-directed immunotherapeutic approaches for eradicating therapeutically resistant GSC populations. ©2012 AACR.

Regulations in the United States for cell transplantation clinical trials in neurological diseases

Institute of Scientific and Technical Information of China (English)

He Zhu; Yuanqing Tan; Qi Gu; Weifang Han; Zhongwen Li; Jason S Meyer; Baoyang Hu

2015-01-01

Objective: This study aimed to use a systematic approach to evaluate the current utilization, safety, and effectiveness of cell therapies for neurological diseases in human. And review the present regulations, considering United States (US) as a representative country, for cell transplantation in neurological disease and discuss the challenges facing the field of neurology in the coming decades. Methods:A detailed search was performed in systematic literature reviews of cellular‐based therapies in neurological diseases, using PubMed, web of science, and clinical trials. Regulations of cell therapy products used for clinical trials were searched from the Food and Drug Administration (FDA) and the National Institutes of Health (NIH). Results: Seven most common types of cell therapies for neurological diseases have been reported to be relatively safe with varying degrees of neurological recovery. And a series of regulations in US for cellular therapy was summarized including preclinical evaluations, sourcing material, stem cell manufacturing and characterization, cell therapy product, and clinical trials. Conclusions:Stem cell‐based therapy holds great promise for a cure of such diseases and will value a growing population of patients. However, regulatory permitting activity of the US in the sphere of stem cells, technologies of regenerative medicine and substitutive cell therapy are selective, theoretical and does not fit the existing norm and rules. Compiled well‐defined regulations to guide the application of stem cell products for clinical trials should be formulated.

12 CFR 404.8 - Initial determination.

Science.gov (United States)

2010-01-01

... 12 Banks and Banking 4 2010-01-01 2010-01-01 false Initial determination. 404.8 Section 404.8 Banks and Banking EXPORT-IMPORT BANK OF THE UNITED STATES INFORMATION DISCLOSURE Procedures for Disclosure of Records Under the Freedom of Information Act. § 404.8 Initial determination. (a) Authority to...

Tumor-initiating cells of breast and prostate origin show alterations in the expression of genes related to iron metabolism

Czech Academy of Sciences Publication Activity Database

Rychtarčíková, Zuzana; Lettlová, Sandra; Tomkova, Veronika; Korenková, Vlasta; Langerová, Lucie; Simonova, Ekaterina; Zjablovskaja, Polina; Alberich-Jorda, Meritxell; Neužil, Jiří; Truksa, Jaroslav

2017-01-01

Roč. 8, č. 4 (2017), s. 6376-6398 ISSN 1949-2553 R&D Projects: GA ČR GA13-28830S; GA ČR GA15-03796S; GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:86652036 ; RVO:68378050 Keywords : tumor-initiating cells * breast cancer * iron metabolism Subject RIV: FD - Oncology ; Hematology; EB - Genetics ; Molecular Biology (UMG-J) OBOR OECD: Cell biology; Cell biology (UMG-J) Impact factor: 5.168, year: 2016

THE FEATURES OF CONNEXINS EXPRESSION IN THE CELLS OF NEUROVASCLAR UNIT IN NORMAL CONDITIONS AND HYPOXIA IN VITRO

Directory of Open Access Journals (Sweden)

A. V. Morgun

2014-01-01

Full Text Available The aim of this research was to assess a role of connexin 43 (Cx43 and associated molecule CD38 in the regulation of cell-cell interactions in the neurovascular unit (NVU in vitro in physiological conditions and in hypoxia.Materials and methods. The study was done using the original neurovascular unit model in vitro. The NVU consisted of three cell types: neurons, astrocytes, and cerebral endothelial cells derived from rats. Hypoxia was induced by incubating cells with sodium iodoacetate for 30 min at37 °C in standard culture conditions.Results. We investigated the role of connexin 43 in the regulation of cell interactions within the NVU in normal and hypoxic injury in vitro. We found that astrocytes were characterized by high levels of expression of Cx43 and low level of CD38 expression, neurons demonstrated high levels of CD38 and low levels of Cx43. In hypoxic conditions, the expression of Cx43 and CD38 in astrocytes markedly increased while CD38 expression in neurons decreased, however no changes were found in endothelial cells. Suppression of Cx43 activity resulted in down-regulation of CD38 in NVU cells, both in physiological conditions and at chemical hypoxia.Conclusion. Thus, the Cx-regulated intercellular NAD+-dependent communication and secretory phenotype of astroglial cells that are the part of the blood-brain barrier is markedly changed in hypoxia.

Increase in white cell and neutrophil counts during the first eighteen weeks of treatment with clozapine in patients admitted to a long-term psychiatric care inpatient unit.

Science.gov (United States)

Capllonch, Adrián; de Pablo, Silvia; de la Torre, Alberto; Morales, Ignacio

Clozapine is an antipsychotic drug that has shown to be more effective than other antipsychotics in the treatment of schizophrenia, but its use is limited due to its side effects, particularly by the risk of causing agranulocytosis. A study was made on the variations in white cell and neutrophil counts in patients treated with clozapine in a Long-term Psychiatric Unit. A retrospective observational study was conducted with a sample of women of our long-term psychiatric care unit who had been treated with clozapine. A study was made on the variations in white cell and neutrophil counts during the first 18 weeks of treatment, as well as the onset of leukopenia, neutropenia, agranulocytosis, and the influence of concomitant drugs. The study included 55 patients on treatment with clozapine. The incidence rate of neutropenia was 1.82% (95% CI; 0.05-10.13). The incidence rate of leukopenia and agranulocytosis was 0%. An increase in white cell and neutrophil counts from baseline to week 3-4 was observed. Only small variations were observed after this time, but the counts remained higher than the initial values. These changes were statistically significant in the white cell count: One-way repeated ANOVA with Greenhouse-Geisser correction F (11.47, 37) = 2.114 (P= .011); and in neutrophils: One-way repeated ANOVA with Greenhouse-Geisser correction F (10.3, 37)=3.312 (P=.0002), and MANOVA F (18, 37)=2.693 (P=.005), ŋ 2 P =0.567. The influence of concomitant drugs (lithium, valproic and biperiden) was not significant on the overall increase found in white cells or neutrophils (MANOVA). Copyright © 2016 SEP y SEPB. Publicado por Elsevier España, S.L.U. All rights reserved.

Reactive Oxygen Species Are Required for Human Mesenchymal Stem Cells to Initiate Proliferation after the Quiescence Exit

Directory of Open Access Journals (Sweden)

O. G. Lyublinskaya

2015-01-01

Full Text Available The present study focuses on the involvement of reactive oxygen species (ROS in the process of mesenchymal stem cells “waking up” and entering the cell cycle after the quiescence. Using human endometrial mesenchymal stem cells (eMSCs, we showed that intracellular basal ROS level is positively correlated with the proliferative status of the cell cultures. Our experiments with the eMSCs synchronized in the G0 phase of the cell cycle revealed a transient increase in the ROS level upon the quiescence exit after stimulation of the cell proliferation. This increase was registered before the eMSC entry to the S-phase of the cell cycle, and elimination of this increase by antioxidants (N-acetyl-L-cysteine, Tempol, and Resveratrol blocked G1–S-phase transition. Similarly, a cell cycle arrest which resulted from the antioxidant treatment was observed in the experiments with synchronized human mesenchymal stem cells derived from the adipose tissue. Thus, we showed that physiologically relevant level of ROS is required for the initiation of human mesenchymal stem cell proliferation and that low levels of ROS due to the antioxidant treatment can block the stem cell self-renewal.

Unit Manning

National Research Council Canada - National Science Library

McGinniss, Mike

2003-01-01

.... This decision combines two crucial initiatives: first, transforming the Army from an individual soldier replacement system to a unit manning system that enhances cohesion and keeps trained soldiers, leaders, and commanders together longer, thereby...

Sikap Bangladesh Dalam Menanggapi Program Unhcr €œUnited Nations Joint Initiative€ Terhadap Penanganan Pengungsi Rohingya (Periode 2006-2011)

OpenAIRE

Olivia, Yessy; ", Mery

2014-01-01

This research explains Bangladesh€™s response about UNHCR€™s €œUnited Nations Joint Initiative€ in handling Rohingya refugees in Bangladesh. Bangladesh is now home to 29.016 Rohingyas. The refugees has caused social and economic problems for Bangladeshi goverment over 33 years. UNJI was proposed by UNHCR to help Rohingyas ang Bangladeshis.The research applies qualitative methods, and case study in this research the data collected through library research, literature studies, official documen...

12 CFR 404.15 - Initial determination.

Science.gov (United States)

2010-01-01

... 12 Banks and Banking 4 2010-01-01 2010-01-01 false Initial determination. 404.15 Section 404.15 Banks and Banking EXPORT-IMPORT BANK OF THE UNITED STATES INFORMATION DISCLOSURE Access to Records Under the Privacy Act of 1974 § 404.15 Initial determination. (a) Time for processing. The Freedom of...

In vivo expansion of co-transplanted T cells impacts on tumor re-initiating activity of human acute myeloid leukemia in NSG mice.

Directory of Open Access Journals (Sweden)

Malte von Bonin

Full Text Available Human cells from acute myeloid leukemia (AML patients are frequently transplanted into immune-compromised mouse strains to provide an in vivo environment for studies on the biology of the disease. Since frequencies of leukemia re-initiating cells are low and a unique cell surface phenotype that includes all tumor re-initiating activity remains unknown, the underlying mechanisms leading to limitations in the xenotransplantation assay need to be understood and overcome to obtain robust engraftment of AML-containing samples. We report here that in the NSG xenotransplantation assay, the large majority of mononucleated cells from patients with AML fail to establish a reproducible myeloid engraftment despite high donor chimerism. Instead, donor-derived cells mainly consist of polyclonal disease-unrelated expanded co-transplanted human T lymphocytes that induce xenogeneic graft versus host disease and mask the engraftment of human AML in mice. Engraftment of mainly myeloid cell types can be enforced by the prevention of T cell expansion through the depletion of lymphocytes from the graft prior transplantation.

Science Granting Councils Initiative: Research uptake | CRDI ...

International Development Research Centre (IDRC) Digital Library (Canada)

The initiative's activities include training, regional exchanges and forums, online training, on-site coaching, and collaborative research. The initiative was developed jointly by IDRC, the United Kingdom's Department for International Development, and South Africa's National Research Foundation. Its ultimate goal is ...

A comparative study of U937 cell size changes during apoptosis initiation by flow cytometry, light scattering, water assay and electronic sizing.

Science.gov (United States)

Yurinskaya, Valentina; Aksenov, Nikolay; Moshkov, Alexey; Model, Michael; Goryachaya, Tatyana; Vereninov, Alexey

2017-10-01

A decrease in flow cytometric forward light scatter (FSC) is commonly interpreted as a sign of apoptotic cell volume decrease (AVD). However, the intensity of light scattering depends not only on the cell size but also on its other characteristics, such as hydration, which may affect the scattering in the opposite way. That makes estimation of AVD by FSC problematic. Here, we aimed to clarify the relationship between light scattering, cell hydration (assayed by buoyant density) and cell size by the Coulter technique. We used human lymphoid cells U937 exposed to staurosporine, etoposide or hypertonic stress as an apoptotic model. An initial increase in FSC was found to occur in apoptotic cells treated with staurosporine and hypertonic solutions; it is accompanied by cell dehydration and is absent in apoptosis caused by etoposide that is consistent with the lack of dehydration in this case. Thus, the effect of dehydration on the scattering signal outweighs the effect of reduction in cell size. The subsequent FSC decrease, which occurred in parallel to accumulation of annexin-positive cells, was similar in apoptosis caused by all three types of inducers. We conclude that an increase, but not a decrease in light scattering, indicates the initial cell volume decrease associated with apoptotic cell dehydration.

Failure mechanisms of additively manufactured porous biomaterials: Effects of porosity and type of unit cell.

Science.gov (United States)

Kadkhodapour, J; Montazerian, H; Darabi, A Ch; Anaraki, A P; Ahmadi, S M; Zadpoor, A A; Schmauder, S

2015-10-01

Since the advent of additive manufacturing techniques, regular porous biomaterials have emerged as promising candidates for tissue engineering scaffolds owing to their controllable pore architecture and feasibility in producing scaffolds from a variety of biomaterials. The architecture of scaffolds could be designed to achieve similar mechanical properties as in the host bone tissue, thereby avoiding issues such as stress shielding in bone replacement procedure. In this paper, the deformation and failure mechanisms of porous titanium (Ti6Al4V) biomaterials manufactured by selective laser melting from two different types of repeating unit cells, namely cubic and diamond lattice structures, with four different porosities are studied. The mechanical behavior of the above-mentioned porous biomaterials was studied using finite element models. The computational results were compared with the experimental findings from a previous study of ours. The Johnson-Cook plasticity and damage model was implemented in the finite element models to simulate the failure of the additively manufactured scaffolds under compression. The computationally predicted stress-strain curves were compared with the experimental ones. The computational models incorporating the Johnson-Cook damage model could predict the plateau stress and maximum stress at the first peak with less than 18% error. Moreover, the computationally predicted deformation modes were in good agreement with the results of scaling law analysis. A layer-by-layer failure mechanism was found for the stretch-dominated structures, i.e. structures made from the cubic unit cell, while the failure of the bending-dominated structures, i.e. structures made from the diamond unit cells, was accompanied by the shearing bands of 45°. Copyright © 2015 Elsevier Ltd. All rights reserved.

The Application of Load-cell Technique in the Study of Armour Unit Responses to Impact Loads Tests

DEFF Research Database (Denmark)

Burcharth, H. F.; Liu, Z.

1995-01-01

The slender, complex types of armour units, such as Tetrapods and Dolosse are widely used for rubble mound breakwaters. Many of the recent failures of such structures were caused by unforeseen early breakage of the units, thus revealing an in balance between the strength (structural integrity......) of the units and the hydraulic stability (resistance to displacements) of the armour layers. Breakage is caused by stresses from static, pulsating and impact loads. Impact load generated stresses are difficult to investigate due to non-linear scaling laws. The paper describes a method by which impact loads on....... slender armour units can be studied. by load-cell technique. Moreover, the paper presents DoJos design diagrams for the prediction of both breakage and hydraulic stability...

Initiation points for cellular deoxyribonucleic acid replication in human lymphoid cells converted by Epstein-Barr virus

International Nuclear Information System (INIS)

Oppenheim, A.; Shlomai, Z.; Ben-Bassat, H.

1981-01-01

Replicon size was estimated in two Epstein-Barr virus (EBV)-negative human lymphoma lines, BJAB and Ramos, and four EBV-positive lines derived from the former ones by infection (conversion) with two viral strains, B95-8 and P3HR-1. Logarithmic cultures were pulse-labeled with [/sup -3/H]thymidine, and the deoxyribonucleic acid was spread on microscopic slides and autoradiographed by the method of Huberman and Riggs. Three of the four EBV-converted cell lines, BJAB/B95-8, Ra/B95-8, and Ra/HRIK, were found to have significantly shorter replicons (41, 21, 54% shorter, respectively), i.e., more initiation points, than their EBV-negative parents. BJAB/HRIK had replicons which were only slightly shorter (11%) than those of BJAB. However, analysis of track length demonstrated that extensive track fusion occurred during the labeling of BJAB/HRIK, implying that its true average replicon size is shorter than the observed value. The results indicate that in analogy to simian virus 40, EBV activates new initiation points for cellular DNA replication in EBV-transformed cells

Initiated chemical vapor deposition of thermoresponsive poly(N-vinylcaprolactam) thin films for cell sheet engineering.

Science.gov (United States)

Lee, Bora; Jiao, Alex; Yu, Seungjung; You, Jae Bem; Kim, Deok-Ho; Im, Sung Gap

2013-08-01

Poly(N-vinylcaprolactam) (PNVCL) is a thermoresponsive polymer known to be nontoxic, water soluble and biocompatible. Here, PNVCL homopolymer was successfully synthesized for the first time by use of a one-step vapor-phase process, termed initiated chemical vapor deposition (iCVD). Fourier transform infrared spectroscopy results showed that radical polymerization took place from N-vinylcaprolactam monomers without damaging the functional caprolactam ring. A sharp lower critical solution temperature transition was observed at 31°C from the iCVD poly(N-vinylcaprolactam) (PNVCL) film. The thermoresponsive PNVCL surface exhibited a hydrophilic/hydrophobic alteration with external temperature change, which enabled the thermally modulated attachment and detachment of cells. The conformal coverage of PNVCL film on various substrates with complex topography, including fabrics and nanopatterns, was successfully demonstrated, which can further be utilized to fabricate cell sheets with aligned cell morphology. The advantage of this system is that cells cultured on such thermoresponsive surfaces could be recovered as an intact cell sheet by simply lowering the temperature, eliminating the need for conventional enzymatic treatments. Copyright © 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Can community change be measured for an outcomes-based initiative? A comparative case study of the success by 6 initiative.

Science.gov (United States)

Minich, Lisa; Howe, Steven; Langmeyer, Daniel; Corcoran, Kevin

2006-12-01

One of the challenges facing nonprofit organizations today is the demand for measurable results. Increasingly, these organizations are focusing less on program outputs and program outcomes in favor of community outcomes or changes demonstrated in the larger community. Success by 6(R) is a popular United Way initiative that emphasizes defining and measuring community outcomes. In this paper, we describe our work with 24 Success by 6(R) initiatives around the country. It is clear that not all of these initiatives are measuring community outcomes. Of those initiatives that are experiencing some success measuring community outcomes, similar measurement strategies are reported. Additionally, our experience suggests several United Way employees express dissatisfaction with the logic model as a framework for defining and measuring community outcomes although no preferred alternative model is identified. Evaluators working with community-wide initiatives must find ways to communicate the differences between program and community outcomes to key stakeholders and funders.

Teledyne Energy Systems, Inc., Proton Exchange Member (PEM) Fuel Cell Engineering Model Powerplant. Test Report: Initial Benchmark Tests in the Original Orientation

Science.gov (United States)

Loyselle, Patricia; Prokopius, Kevin

2011-01-01

Proton Exchange Membrane (PEM) fuel cell technology is the leading candidate to replace the alkaline fuel cell technology, currently used on the Shuttle, for future space missions. During a 5-yr development program, a PEM fuel cell powerplant was developed. This report details the initial performance evaluation test results of the powerplant.

Conspicuous variation of the lattice unit cell in the pavonite homologous series and its relation with cation/anion occupational modulations

Energy Technology Data Exchange (ETDEWEB)

Perez-Mato, J.M., E-mail: jm.perez-mato@ehu.es [Dpto. de Física de la Materia Condensada, Facultad de Ciencia y Tecnología, UPV/EHU, Apartado 644, 48080 Bilbao (Spain); Elcoro, Luis [Dpto. de Física de la Materia Condensada, Facultad de Ciencia y Tecnología, UPV/EHU, Apartado 644, 48080 Bilbao (Spain); Makovicky, Emil [Department of Geography and Geology, University of Copenhagen, Øster Voldgade 10, DK-1350 Copenhagen K (Denmark); Topa, Dan [Department of Materials Research and Physics, University of Salzburg, Hellbrunnerstrasse 34, 5020 Salzburg (Austria); Petříček, Václav [Institute of Physics, Academy of Sciences of the Czech Republic v.v.i., Na Slovance 2, 182 21 Praha 8 (Czech Republic); Madariaga, Gotzon [Dpto. de Física de la Materia Condensada, Facultad de Ciencia y Tecnología, UPV/EHU, Apartado 644, 48080 Bilbao (Spain)

2013-06-01

Highlights: ► Strong non-uniform variation of unit cell parameters in the pavonite homologous series. ► Conspicuous unit cell variation due to an underlying sub-lattice with cation/anion occupation. ► A modulated model common to the whole series using the superspace formalism proposed. ► Model successfully applied to the {sup 7}P pavonite Ag{sub 3}(Bi,Pb){sub 7}S{sub 12}. ► The model can be applied in a predictive way to other members of the family. - Abstract: The pavonites is a homologous series of sulfosalts with galena-like modules of variable size. A survey of their unit cells reveals that they are severely constrained by the metrics of an underlying common average sublattice. The unit cell of any compound of the series accommodates with high precision an integer number of approximately equal subcells. This explains a peculiar non-uniform variation of the unit cell parameters within the series and evidences that the interface between the galena-like modules, despite having a very different topology, approximately maintains the subperiodicity of the modules, and must therefore be subject to strong steric restrictions. It also implies that cations and anions occupy the nodes of the observed common underlying average sublattice according to a striking alternate cation/anion occupational modulation. This is the starting point for a description of these materials as modulated structures, which can make a proficient use of the approximate atomic positional non-crystallographic correlations caused by their modular character. Under this approach only four parameters suffice to define a realistic approximate model of any member of the series. A full structural characterization of any of the compounds only requires the determination of additional small/smooth modulations. As an example, the case of the {sup 7}P pavonite Ag{sub 3}Bi{sub 6.2}Pb{sub 0.8}S{sub 12}, is analyzed.

Long-term persistence of quality improvements for an intensive care unit communication initiative using the VALUE strategy.

Science.gov (United States)

Wysham, Nicholas G; Mularski, Richard A; Schmidt, David M; Nord, Shirley C; Louis, Deborah L; Shuster, Elizabeth; Curtis, J Randall; Mosen, David M

2014-06-01

Communication in the intensive care unit (ICU) is an important component of quality ICU care. In this report, we evaluate the long-term effects of a quality improvement (QI) initiative, based on the VALUE communication strategy, designed to improve communication with family members of critically ill patients. We implemented a multifaceted intervention to improve communication in the ICU and measured processes of care. Quality improvement components included posted VALUE placards, templated progress note inclusive of communication documentation, and a daily rounding checklist prompt. We evaluated care for all patients cared for by the intensivists during three separate 3 week periods, pre, post, and 3 years following the initial intervention. Care delivery was assessed in 38 patients and their families in the pre-intervention sample, 27 in the post-intervention period, and 41 in follow-up. Process measures of communication showed improvement across the evaluation periods, for example, daily updates increased from pre 62% to post 76% to current 84% of opportunities. Our evaluation of this quality improvement project suggests persistence and continued improvements in the delivery of measured aspects of ICU family communication. Maintenance with point-of-care-tools may account for some of the persistence and continued improvements. Copyright © 2014 Elsevier Inc. All rights reserved.

Effect of initial void shape on ductile failure in a shear field

DEFF Research Database (Denmark)

Tvergaard, Viggo

2015-01-01

For voids in a shear field unit cell model analyses have been used to show that ductile failure is predicted even though the stress triaxiality is low or perhaps negative, so that the void volume fraction does not grow during deformation. Here, the effect of the void shape is studied by analyzing...... with circular cross-section, i.e. the voids in shear flatten out to micro-cracks, which rotate and elongate until interaction with neighboring micro-cracks gives coalescence. Even though the mechanism of ductile failure is the same, the load carrying capacity predicted, for the same initial void volume fraction...

The Western Canada Fuel Cell Initiative (WCFCI)

International Nuclear Information System (INIS)

Birss, V.; Chuang, K.

2006-01-01

Vision: Western Canada will become an international centre for stationary power generation technology using high temperature fuel cells that use a wide variety of fossil and biomass fuels. Current research areas of investigation: 1. Clean efficient use of hydrocarbons 2. Large-scale electricity generation 3. CO2 sequestration 4. Direct alcohol fuel cells 5. Solid oxide fuel cells. (author)

Non‐Canonical Replication Initiation: You’re Fired!

Directory of Open Access Journals (Sweden)

Bazilė Ravoitytė

2017-01-01

Full Text Available The division of prokaryotic and eukaryotic cells produces two cells that inherit a perfect copy of the genetic material originally derived from the mother cell. The initiation of canonical DNA replication must be coordinated to the cell cycle to ensure the accuracy of genome duplication. Controlled replication initiation depends on a complex interplay of cis‐acting DNA sequences, the so‐called origins of replication (ori, with trans‐acting factors involved in the onset of DNA synthesis. The interplay of cis‐acting elements and trans‐acting factors ensures that cells initiate replication at sequence‐specific sites only once, and in a timely order, to avoid chromosomal endoreplication. However, chromosome breakage and excessive RNA:DNA hybrid formation can cause breakinduced (BIR or transcription‐initiated replication (TIR, respectively. These non‐canonical replication events are expected to affect eukaryotic genome function and maintenance, and could be important for genome evolution and disease development. In this review, we describe the difference between canonical and non‐canonical DNA replication, and focus on mechanistic differences and common features between BIR and TIR. Finally, we discuss open issues on the factors and molecular mechanisms involved in TIR.

Using Human Stem Cells to Study the Role of the Stroma in the Initiation of Prostate Cancer

Science.gov (United States)

2011-03-01

Edinburgh, UK (Invited Speaker) 2. Risbridger GP (2009) 9th International Congress of Andrology, Barcelona , Spain (Invited Speaker) – “From Human Stem...malignant cancer- initiating cells. Cancer Research 68 9703–9711. (doi:10. 1158/0008-5472.CAN-08-3084) Verhagen AP, Aalders TW, Ramaekers FC , Debruyne

On-site fuel cell field test support program

Science.gov (United States)

Staniunas, J. W.; Merten, G. P.

1982-01-01

In order to assess the impact of grid connection on the potential market for fuel cell service, applications studies were conducted to identify the fuel cell operating modes and corresponding fuel cell sizing criteria which offer the most potential for initial commercial service. The market for grid-connected fuel cell service was quantified using United's market analysis program and computerized building data base. Electric and gas consumption data for 268 buildings was added to our surveyed building data file, bringing the total to 407 buildings. These buildings were analyzed for grid-isolated and grid-connected fuel cell service. The results of the analyses indicated that the nursing home, restaurant and health club building sectors offer significant potential for fuel cell service.

Immunohistochemical study of jejunal graft mucosa cell populations during the initial adaptation phase in the host body in rats.

Science.gov (United States)

Tóth, Stefan; Jonecová, Zuzana; Varga, Ján; Staško, Pavel; Kovalčinová, Barbora; Maretta, Milan; Leško, Dušan; Veselá, Jarmila

2013-10-01

The character of the changes in cell populations within the jejunal graft mucosa during the initial adaptation phase in the host body was investigated. 24 adult male Wistar rats underwent intestinal heterotopic allotransplantation. Aorto-aortal and porto-caval anastomoses were performed using the end-to-side microsurgery technique. Graft tissues were compared to the intestinal tissues of the recipients. This study demonstrates that: (1) Distinct injury to the graft mucosa 1h after transplantation was accompanied by significant reduction in numbers of epithelial secretory cell populations. The injury was more intense in the mesenteric portion. Six hours after transplantation the graft mucosa was covered by a continuous epithelium, but the number of goblet and Paneth cells was found to be less than 30% of that in the recipient epithelium. (2) In comparison with recipients, myeloperoxidase-positive cell numbers increased significantly in the graft mucosa 1 h after transplantation. In the epithelial layer, denudation and destruction of villi was associated with a significant reduction in intraepithelial lymphocyte numbers. A significant decrease in mucosal mast cell numbers was detected 6 h after transplantation. They attained only 10% of the number found in the recipients. (3) Time-dependent changes in the graft mucosa revealed that CD163-positive cells increased significantly in the graft mucosa during 6 h after transplantation and reached the level found in the recipients. In contrast, the myeloperoxidase-positive cell population significantly decreased in the graft mucosa within the initial 6 h. Copyright © 2013 Elsevier GmbH. All rights reserved.

On the cells of origin of radiogenic thyroid cancer

International Nuclear Information System (INIS)

Clifton, K.H.; Domann, F.E.; Groch, K.M.

1991-01-01

A major effort has been devoted to studies of the origins of radiogenic and hormonally-induced cancer at the cellular level in vivo. The studies has provided evidence that the functional thyroid follicules (follicular units, FU) which are formed in grafts of monodispersed rat thyroid cells, and hence the thyroid tumors which later develop in such grafts, are clonal in origin. Transplantation assays indicate that the clonogens comprise 1% of the cells in monodispersed suspensions of normal thyroid tissue. Carcinogenesis studies show that neoplastic initiation of thyroid clonogens by radiation is a commo event. Promotion-progression to cancer from radiation initiated clonogens has, however, been shown to be inversely related to the total grafted thyroid cell number. It is thus important to further define the physiology and population kinetics of the thyroid clonogens under different hormonal conditions both in situ and following transplantion. This report briefly summarizes recent data on (a) local cell-cell and remote hormonal feedback interactions during neoplastic promotion of initiated cells among the progeny of grafted clonogens in multicellular FU; (b) clonogenic cell population kinetics in situ during goitrogenesis and goiter involution; and (c) the reestablishment of the thyroid-hypothalamus-pituitary hormonal feedback system in thyroid cell-grafted thyroidectomized rats and its dependence on the formation of FU by the grafted clonogens. These results support the conclusion that the thyroid gland contains a small sub-population of clonogenic epithelial cells which posess many stem cell-like characteristics. (N.K.)

Akt2 and nucleophosmin/B23 function as an oncogenic unit in human lung cancer cells

International Nuclear Information System (INIS)

Kim, Chung Kwon; Nguyen, Truong L.X.; Lee, Sang Bae; Park, Sang Bum; Lee, Kyung-Hoon; Cho, Sung-Woo; Ahn, Jee-Yin

2011-01-01

The signaling network of protein kinase B(PKB)/Akt has been implicated in survival of lung cancer cells. However, understanding the relative contribution of the different isoform of Akt network is nontrival. Here, we report that Akt2 is highly expressed in human lung adenocarcinoma cell line A549 cells. Suppression of Akt2 expression in A549 cells results in notable inhibition of cell poliferation, soft agar growth, and invasion, accompanying by a decrease of nucleophosmin/B23 protein. Overexpression of Akt1 restores cancerous growth of A549 cells in B23-knockdown (KD) cells while Akt2 overexpression did not restore proliferating potential in cells with downregulated B23, thus suggesting Akt2 requires B23 to drive proliferation of lung cancer cell. Loss of functional Akt2 and B23 has similar defects on cell proliferation, apoptotic resistance and cell cycle regulation, while loss of Akt1 has less defects on cell proliferation, survial and cell cycle progression in A549 cells. Moreover, overexpression of B23 rescues the proliferative block induced as a consequence of loss of Akt2. Thus our data suggest that Akt2/B23 functions as an oncogenic unit to drive tumorigenesis of A549 lung cancer cells.

Cold/menthol TRPM8 receptors initiate the cold-shock response and protect germ cells from cold-shock-induced oxidation.

Science.gov (United States)

Borowiec, Anne-Sophie; Sion, Benoit; Chalmel, Frédéric; D Rolland, Antoine; Lemonnier, Loïc; De Clerck, Tatiana; Bokhobza, Alexandre; Derouiche, Sandra; Dewailly, Etienne; Slomianny, Christian; Mauduit, Claire; Benahmed, Mohamed; Roudbaraki, Morad; Jégou, Bernard; Prevarskaya, Natalia; Bidaux, Gabriel

2016-09-01

Testes of most male mammals present the particularity of being externalized from the body and are consequently slightly cooler than core body temperature (4-8°C below). Although, hypothermia of the testis is known to increase germ cells apoptosis, little is known about the underlying molecular mechanisms, including cold sensors, transduction pathways, and apoptosis triggers. In this study, using a functional knockout mouse model of the cold and menthol receptors, dubbed transient receptor potential melastatine 8 (TRPM8) channels, we found that TRPM8 initiated the cold-shock response by differentially modulating cold- and heat-shock proteins. Besides, apoptosis of germ cells increased in proportion to the cooling level in control mice but was independent of temperature in knockout mice. We also observed that the rate of germ cell death correlated positively with the reactive oxygen species level and negatively with the expression of the detoxifying enzymes. This result suggests that the TRPM8 sensor is a key determinant of germ cell fate under hypothermic stimulation.-Borowiec, A.-S., Sion, B., Chalmel, F., Rolland, A. D., Lemonnier, L., De Clerck, T., Bokhobza, A., Derouiche, S., Dewailly, E., Slomianny, C., Mauduit, C., Benahmed, M., Roudbaraki, M., Jégou, B., Prevarskaya, N., Bidaux, G. Cold/menthol TRPM8 receptors initiate the cold-shock response and protect germ cells from cold-shock-induced oxidation. © The Author(s).

Characterization and propagation of tumor initiating cells derived from colorectal liver metastases: trials, tribulations and a cautionary note.

Directory of Open Access Journals (Sweden)

Mark I James

Full Text Available Tumor initiating cells (TIC are increasingly being put forward as a potential target for intervention within colorectal cancer. Whilst characterisation and outgrowth of these cells has been extensively undertaken in primary colorectal cancers, few data are available describing characteristics within the metastatic setting. Tissue was obtained from patients undergoing surgical resection for colorectal liver metastases, and processed into single cell suspension for assessment. Tumor initiating cells from liver metastases were characterised using combinations of EPCAM, Aldehyde dehydrogenase activity, CD133 and CD26. CD133 expression was significantly lower in patients who had received chemotherapy, but this was accounted for by a decrease observed in the male patient cohort only. ALDHhigh populations were rare (0.4 and 0.3% for EPCAM+/ALDHhigh/CD133- and EPCAM+/ALDHhigh/CD133+ populations respectively and below the limits of detection in 28% of samples. Spheroid outgrowth of metastatic tumor cells across all samples could not be readily achieved using standard spheroid-formation techniques, thus requiring further method validation to reliably propagate cells from the majority of tissues. Spheroid formation was not enhanced using additional growth factors or fibroblast co-culture, but once cells were passaged through NOD-SCID mice, spheroid formation was observed in 82% samples, accompanied by a significant increase in CD26. Order of spheroid forming ability was ALDHhigh>CD133>CD26. Samples sorted by these markers each had the ability to reform ALDHhigh, CD133 and CD26 positive populations to a similar extent, suggestive of a high degree of plasticity for each population. Ex vivo TIC models are increasingly being utilised to assess efficacy of therapeutic interventions. It is therefore essential that such investigations use well-characterised models that are able to sustain TIC populations across a large patient cohort in order that the inherent

Research of the impact of coupling between unit cells on performance of linear-to-circular polarization conversion metamaterial with half transmission and half reflection

Science.gov (United States)

Guo, Mengchao; Zhou, Kan; Wang, Xiaokun; Zhuang, Haiyan; Tang, Dongming; Zhang, Baoshan; Yang, Yi

2018-04-01

In this paper, the impact of coupling between unit cells on the performance of linear-to-circular polarization conversion metamaterial with half transmission and half reflection is analyzed by changing the distance between the unit cells. An equivalent electrical circuit model is then built to explain it based on the analysis. The simulated results show that, when the distance between the unit cells is 23 mm, this metamaterial converts half of the incident linearly-polarized wave into reflected left-hand circularly-polarized wave and converts the other half of it into transmitted left-hand circularly-polarized wave at 4.4 GHz; when the distance is 28 mm, this metamaterial reflects all of the incident linearly-polarized wave at 4.4 GHz; and when the distance is 32 mm, this metamaterial converts half of the incident linearly-polarized wave into reflected right-hand circularly-polarized wave and converts the other half of it into transmitted right-hand circularly-polarized wave at 4.4 GHz. The tunability is realized successfully. The analysis shows that the changes of coupling between unit cells lead to the changes of performance of this metamaterial. The coupling between the unit cells is then considered when building the equivalent electrical circuit model. The built equivalent electrical circuit model can be used to perfectly explain the simulated results, which confirms the validity of it. It can also give help to the design of tunable polarization conversion metamaterials.

FY 10 Multifamily Initial Endorsements

Data.gov (United States)

Department of Housing and Urban Development — In FY 2010, HUD's Multifamily's 18 Hubs initially endorsed 1011 loans totaling $11.3 billion and providing 170,672 units/ beds. FY 10's $11.3 billion is the highest...

NFATc4 Regulates Sox9 Gene Expression in Acinar Cell Plasticity and Pancreatic Cancer Initiation

Directory of Open Access Journals (Sweden)

Elisabeth Hessmann

2016-01-01

Full Text Available Acinar transdifferentiation toward a duct-like phenotype constitutes the defining response of acinar cells to external stress signals and is considered to be the initial step in pancreatic carcinogenesis. Despite the requirement for oncogenic Kras in pancreatic cancer (PDAC development, oncogenic Kras is not sufficient to drive pancreatic carcinogenesis beyond the level of premalignancy. Instead, secondary events, such as inflammation-induced signaling activation of the epidermal growth factor (EGFR or induction of Sox9 expression, are required for tumor formation. Herein, we aimed to dissect the mechanism that links EGFR signaling to Sox9 gene expression during acinar-to-ductal metaplasia in pancreatic tissue adaptation and PDAC initiation. We show that the inflammatory transcription factor NFATc4 is highly induced and localizes in the nucleus in response to inflammation-induced EGFR signaling. Moreover, we demonstrate that NFATc4 drives acinar-to-ductal conversion and PDAC initiation through direct transcriptional induction of Sox9. Therefore, strategies designed to disrupt NFATc4 induction might be beneficial in the prevention or therapy of PDAC.

Cell-free DNA, inflammation, and the initiation of spontaneous term labor.

Science.gov (United States)

Herrera, Christina A; Stoerker, Jay; Carlquist, John; Stoddard, Gregory J; Jackson, Marc; Esplin, Sean; Rose, Nancy C

2017-11-01

Hypomethylated cell-free DNA from senescent placental trophoblasts may be involved in the activation of the inflammatory cascade to initiate labor. To determine the changes in cell-free DNA concentrations, the methylation ratio, and inflammatory markers between women in labor at term vs women without labor. In this prospective cohort study, eligible participants carried a nonanomalous singleton fetus. Women with major medical comorbidity, preterm labor, progesterone use, aneuploidy, infectious disease, vaginal bleeding, abdominal trauma, or invasive procedures during the pregnancy were excluded. Maternal blood samples were collected at 28 weeks, 36 weeks, and at admission for delivery. Total cell-free DNA concentration, methylation ratio, and interleukin-6 were analyzed. The primary outcome was the difference in methylation ratio in women with labor vs without labor. Secondary outcomes included the longitudinal changes in these biomarkers corresponding to labor status. A total of 55 women were included; 20 presented in labor on admission and 35 presented without labor. Women in labor had significantly greater methylation ratio (P = .001) and interleukin-6 (P < .001) on admission for delivery than women without labor. After we controlled for body mass index and maternal age, methylation ratio (adjusted relative risk, 1.38; 95% confidence interval, 1.13 to 1.68) and interleukin-6 (adjusted relative risk, 1.12, 95% confidence interval, 1.07 to 1.17) remained greater in women presenting in labor. Total cell-free DNA was not significantly different in women with labor compared with women without. Longitudinally, total cell-free DNA (P < .001 in labor, P = .002 without labor) and interleukin-6 (P < .001 in labor, P = .01 without labor) increased significantly across gestation in both groups. The methylation ratio increased significantly in women with labor from 36 weeks to delivery (P = .02). Spontaneous labor at term is associated with a greater cell-free DNA

OECD benchmark a of MOX fueled PWR unit cells using SAS2H, triton and mocup

International Nuclear Information System (INIS)

Ganda, F.; Greenspan, A.

2005-01-01

Three code systems are tested by applying them to calculate the OECD PWR MOX unit cell benchmark A. The codes tested are the SAS2H code sequence of the SCALE5 code package using 44 group library, MOCUP (MCNP4C + ORIGEN2), and the new TRITON depletion sequence of SCALE5 using 238 group cross sections generated using CENTRM with continuous energy cross sections. The burnup-dependent k ∞ and actinides concentration calculated by all three code-systems were found to be in good agreement with the OECD benchmark average results. Limited results were calculated also with the WIMS-ANL code package. WIMS-ANL was found to significantly under-predict k ∞ as well as the concentration of Pu 242 , consistently with the predictions of the WIMS-LWR reported by two of the OECD benchmark participants. Additionally, SAS2H is benchmarked against MOCUP for a hydride fuel containing unit cell, giving very satisfactory agreement. (authors)

A battery-fuel cell hybrid auxiliary power unit for trucks: Analysis of direct and indirect hybrid configurations

International Nuclear Information System (INIS)

Samsun, Remzi Can; Krupp, Carsten; Baltzer, Sidney; Gnörich, Bruno; Peters, Ralf; Stolten, Detlef

2016-01-01

Highlights: • A battery-fuel cell hybrid auxiliary power unit for heavy duty vehicles is reported. • Comparison of direct and indirect hybrids using representative load profiles. • Evaluation based on validated fuel cell system and battery models. • Indirect hybrid with constant fuel cell load yields 29.3% hybrid system efficiency. • Fuel cell should be pre-heated using waste heat from the diesel engine during drive. - Abstract: The idling operation of engines in heavy duty vehicles to cover electricity demand during layovers entails significant fuel consumption and corresponding emissions. Indeed, this mode of operation is highly inefficient and a noteworthy contributor to the transportation sector’s aggregate carbon dioxide emissions. Here, a potential solution to this wasteful practice is outlined in the form of a hybrid battery-fuel cell system for application as an auxiliary power unit for trucks. Drawing on experimentally-validated fuel cell and battery models, several possible hybrid concepts are evaluated and direct and indirect hybrid configurations analyzed using a representative load profile. The results indicate that a direct hybrid configuration is only applicable if the load demand profile does not deviate strongly from the assumed profile. Operation of an indirect hybrid with a constant fuel cell load yields the greatest hybrid system efficiency, at 29.3%, while battery size could be reduced by 87% if the fuel cell is operated at the highest dynamics. Maximum efficiency in truck applications can be achieved by pre-heating the system prior to operation using exhaust heat from the motor, which increased system efficiency from 25.3% to 28.1%, including start-up. These findings confirm that hybrid systems could offer enormous fuel savings and constitute a sizeable step on the path toward energy-efficient and environmentally-friendly heavy duty vehicles that does not necessitate a fuel switch.

In vitro Th1 and Th2 cell polarization is severely influenced by the initial ratio of naïve and memory CD4+ T cells

DEFF Research Database (Denmark)

Blom, Lars; Poulsen, Lars K.

2013-01-01

by even small percentages (99% naïve CD4+ T cells resulted in better Th1 and Th2 polarization with significant reduced fractions of IL-4+ and IFN-γ+ CD4+ T cells, respectively. Moreover, the Th2 primed >99% naïve CD4+ T cells showed significantly higher ratio of IL-4+:IFN-γ+ (>4 fold) and GATA-3:+T......-bet+ (>3 fold) CD4+ T cells when compared with the standard purified >90-95% naïve CD4+ T cells primed under the same culture conditions. This suggests immunomagnetic bead separation, a low cost and easy available technique, with few modifications to the manufacturer's protocol as an attractive alternative...... for laboratories not having a cell sorter. Taken together, we report that it is essential to use rigorously purified (>99%) naïve CD4+ T cells for optimal initial in vitro Th1 and Th2 priming....

Barriers and facilitators to implementing the Baby-Friendly hospital initiative in neonatal intensive care units.

Science.gov (United States)

Benoit, Britney; Semenic, Sonia

2014-01-01

To explore manager, educator, and clinical leader perceptions of barriers and facilitators to implementing Baby-Friendly practice in the neonatal intensive care unit (NICU). Qualitative, descriptive design. Two university-affiliated level-III NICUs in Canada. A purposive sample of 10 medical and nursing managers, nurse educators, lactation consultants, and neonatal nurse practitioners. In-depth, semistructured interviews transcribed and analyzed using qualitative content analysis. Participants valued breastfeeding and family-centered care yet identified numerous contextual barriers to Baby-Friendly care including infant health status, parent/infant separation, staff workloads and work patterns, gaps in staff knowledge and skills, and lack of continuity of breastfeeding support. Facilitators included breastfeeding education, breastfeeding champions, and interprofessional collaboration. Despite identifying numerous barriers, participants recognized the potential value of expanding the Baby-Friendly Hospital Initiative (BFHI) to the NICU setting. Recommendations include promoting BFHI as a facilitator of family-centered care, interdisciplinary staff education, increasing access to lactation consultants, and establishing a group of NICU champions dedicated to BFHI implementation. © 2014 AWHONN, the Association of Women's Health, Obstetric and Neonatal Nurses.

DNA replication initiator Cdc6 also regulates ribosomal DNA transcription initiation.

Science.gov (United States)

Huang, Shijiao; Xu, Xiaowei; Wang, Guopeng; Lu, Guoliang; Xie, Wenbing; Tao, Wei; Zhang, Hongyin; Jiang, Qing; Zhang, Chuanmao

2016-04-01

RNA-polymerase-I-dependent ribosomal DNA (rDNA) transcription is fundamental to rRNA processing, ribosome assembly and protein synthesis. However, how this process is initiated during the cell cycle is not fully understood. By performing a proteomic analysis of transcription factors that bind RNA polymerase I during rDNA transcription initiation, we identified that the DNA replication initiator Cdc6 interacts with RNA polymerase I and its co-factors, and promotes rDNA transcription in G1 phase in an ATPase-activity-dependent manner. We further showed that Cdc6 is targeted to the nucleolus during late mitosis and G1 phase in a manner that is dependent on B23 (also known as nucleophosmin, NPM1), and preferentially binds to the rDNA promoter through its ATP-binding domain. Overexpression of Cdc6 increases rDNA transcription, whereas knockdown of Cdc6 results in a decreased association of both RNA polymerase I and the RNA polymerase I transcription factor RRN3 with rDNA, and a reduction of rDNA transcription. Furthermore, depletion of Cdc6 impairs the interaction between RRN3 and RNA polymerase I. Taken together, our data demonstrate that Cdc6 also serves as a regulator of rDNA transcription initiation, and indicate a mechanism by which initiation of rDNA transcription and DNA replication can be coordinated in cells. © 2016. Published by The Company of Biologists Ltd.

Mitochondrially targeted vitamin E succinate efficiently kills breast tumour-initiating cells in a complex II-dependent manner

Czech Academy of Sciences Publication Activity Database

Yan, B.; Stantic, M.; Zobalová, Renata; Bezawork-Geleta, A.; Stapelberg, M.; Stursa, J.; Prokopová, Kateřina; Dong, L.; Neužil, Jiří

2015-01-01

Roč. 15, č. 401 (2015) ISSN 1471-2407 R&D Projects: GA MZd NT14078; GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:86652036 Keywords : Tumour-initiating cells * Mitochondrially targeted vitamin E succinate * Complex II Subject RIV: FD - Oncology ; Hematology Impact factor: 3.265, year: 2015

Super Unit Cells in Aperture-Based Metamaterials

Directory of Open Access Journals (Sweden)

Dragan Tanasković

2015-01-01

Full Text Available An important class of electromagnetic metamaterials are aperture-based metasurfaces. Examples include extraordinary optical transmission arrays and double fishnets with negative refractive index. We analyze a generalization of such metamaterials where a simple aperture is now replaced by a compound object formed by superposition of two or more primitive objects (e.g., rectangles, circles, and ellipses. Thus obtained “super unit cell” shows far richer behavior than the subobjects that comprise it. We show that nonlocalities introduced by overlapping simple subobjects can be used to produce large deviations of spectral dispersion even for small additive modifications of the basic geometry. Technologically, some super cells may be fabricated by simple spatial shifting of the existing photolithographic masks. In our investigation we applied analytical calculations and ab initio finite element modeling to prove the possibility to tailor the dispersion including resonances for plasmonic nanocomposites by adjusting the local geometry and exploiting localized interactions at a subwavelength level. Any desired form could be defined using simple primitive objects, making the situation a geometrical analog of the case of series expansion of a function. Thus an additional degree of tunability of metamaterials is obtained. The obtained designer structures can be applied in different fields like waveguiding and sensing.

Modulation of translation-initiation in CHO-K1 cells by rapamycin-induced heterodimerization of engineered eIF4G fusion proteins.

Science.gov (United States)

Schlatter, Stefan; Senn, Claudia; Fussenegger, Martin

2003-07-20

Translation-initiation is a predominant checkpoint in mammalian cells which controls protein synthesis and fine-tunes the flow of information from gene to protein. In eukaryotes, translation-initiation is typically initiated at a 7-methyl-guanylic acid cap posttranscriptionally linked to the 5' end of mRNAs. Alternative cap-independent translation-initiation involves 5' untranslated regions (UTR) known as internal ribosome entry sites, which adopt a particular secondary structure. Translation-initiating ribosome assembly at cap or IRES elements is mediated by a multiprotein complex of which the initiation factor 4F (eIF4F) consisting of eIF4A (helicase), eIF4E (cap-binding protein), and eIF4G is a major constituent. eIF4G is a key target of picornaviral protease 2A, which cleaves this initiation factor into eIF4G(Delta) and (Delta)eIF4G to redirect the cellular translation machinery exclusively to its own IRES-containing transcripts. We have designed a novel translation control system (TCS) for conditional as well as adjustable translation of cap- and IRES-dependent transgene mRNAs in mammalian cells. eIF4G(Delta) and (Delta)eIF4G were fused C- and N-terminally to the FK506-binding protein (FKBP) and the FKBP-rapamycin-binding domain (FRB) of the human FKBP-rapamycin-associated protein (FRAP), respectively. Rapamycin-induced heterodimerization of eIF4G(Delta)-FKBP and FRB-(Delta)eIF4G fusion proteins reconstituted a functional chimeric elongation factor 4G in a dose-dependent manner. Rigorous quantitative expression analysis of cap- and IRES-dependent SEAP- (human placental secreted alkaline phosphatase) and luc- (Photinus pyralis luciferase) encoding reporter constructs confirmed adjustable translation control and revealed increased production of desired proteins in response to dimerization-induced heterologous eIF4G in Chinese hamster ovary (CHO-K1) cells. Copyright 2003 Wiley Periodicals, Inc. Biotechnol Bioeng 83: 210-225, 2003.

Silicon Nanowire/Polymer Hybrid Solar Cell-Supercapacitor: A Self-Charging Power Unit with a Total Efficiency of 10.5.

Science.gov (United States)

Liu, Ruiyuan; Wang, Jie; Sun, Teng; Wang, Mingjun; Wu, Changsheng; Zou, Haiyang; Song, Tao; Zhang, Xiaohong; Lee, Shuit-Tong; Wang, Zhong Lin; Sun, Baoquan

2017-07-12

An integrated self-charging power unit, combining a hybrid silicon nanowire/polymer heterojunction solar cell with a polypyrrole-based supercapacitor, has been demonstrated to simultaneously harvest solar energy and store it. By efficiency enhancement of the hybrid nanowire solar cells and a dual-functional titanium film serving as conjunct electrode of the solar cell and supercapacitor, the integrated system is able to yield a total photoelectric conversion to storage efficiency of 10.5%, which is the record value in all the integrated solar energy conversion and storage system. This system may not only serve as a buffer that diminishes the solar power fluctuations from light intensity, but also pave its way toward cost-effective high efficiency self-charging power unit. Finally, an integrated device based on ultrathin Si substrate is demonstrated to expand its feasibility and potential application in flexible energy conversion and storage devices.