"The difference is in the tomato at the end": Understanding the motivations and practices of cannabis growers operating within Belgian Cannabis Social Clubs.

PubMed

Pardal, Mafalda

2018-03-11

In Belgium, Cannabis Social Clubs (CSCs) collectively organize the cultivation and distribution of cannabis for the personal use of their members. In this paper we seek to improve understanding of the motivations and practices of cannabis growers operating within CSCs, shedding light on the cultivation process. We draw on data gathered through face-to-face semi-structured interviews with the directors of seven active Belgian CSCs (n = 21) and CSC growers (n = 23). These data are complemented by additional fieldwork and a review of policies relating to CSCs', including bylaws and growing protocols. The Belgian CSCs rely on single and multiple in-house grower arrangements. Most CSC growers had been cultivating cannabis prior to joining their current CSC, albeit growing in different contexts (non-commercial and commercial). The CSC growers discussed both ideological and pragmatic motives for operating within a CSC. Cultivation took place indoors and followed organic practices. Despite their small-scale (20 plants on average), the grow sites used specialized equipment. The growers reported receiving financial compensation to cover production costs. This paper offers new insights into a particular sector of domestic cannabis cultivation - CSC growers and their practices within those collectives - which has not been studied previously. The Belgian CSCs have decentralized production among small-scale grow sites, at a size comparable to that found in other small-scale cultivation studies. In terms of motivations and practices, CSC growers share some features typically ascribed to small-scale cannabis cultivators. At the same time, CSC growers seemed particularly engaged with the CSC model and willing to adhere to the (self-)regulated practices developed by the organizations. This had implications for the way cultivation was organized and for the role of the grower within the CSC. Copyright © 2018 Elsevier B.V. All rights reserved.

Central serous chorioretinopathy and phosphodiesterase-5 inhibitors: a case-control postmarketing surveillance study.

PubMed

French, Dustin D; Margo, Curtis E

2010-02-01

The purpose of this study was to determine if there is an increased risk of central serous chorioretinopathy (CSC) associated with prescription exposure to phosphodiesterase-5 (PDE-5) inhibitors. A case-control study linking 2 National Veterans Health Administration databases (clinical and pharmacy) for fiscal years 2004 to 2005. The likelihood of past exposure to PDE-5 inhibitors among newly diagnosed patients with CSC, identified through International Classification of Diseases, 9th Edition, Clinical Modification codes, was compared with 2 age-matched control groups after excluding subjects with risk factors for CSC. Among 577 men, aged 59 years and younger with newly diagnosed CSC during the study year, 111 were prescribed a PDE-5 inhibitor (19.2%). The proportions of age-matched controls prescribed a PDE-5 inhibitor in the 2 groups were 18.5% and 21.5%. The odds ratio of exposure was 1.05 (95% confidence limit: 0.74-1.22) and 0.87 (95% confidence limit: 0.68-1.12). Patients with CSC had no increase in prescription exposure to PDE-5 inhibitors than did age-matched control subjects. Although the findings in this study do not support an association between CSC and PDE-5 inhibitors, postmarketing surveillance methods for drug-related side effects have acknowledged limitations.

The connection between the primary care and the physical activity sector: professionals' perceptions.

PubMed

Leenaars, Karlijn E F; Florisson, Annemiek M E; Smit, Eva; Wagemakers, Annemarie; Molleman, Gerard R M; Koelen, Maria A

2016-09-21

To stimulate physical activity (PA) and guide primary care patients towards local PA facilities, Care Sport Connectors (CSC), to whom a broker role has been ascribed, were introduced in 2012 in the Netherlands. The aim of this study is to assess perceptions of primary care, welfare, and sport professionals towards the CSC role and the connection between the primary care and the PA sector. Nine focus groups were held with primary care, welfare and sport professionals within the CSC network. In these focus groups the CSC role and the connection between the sectors were discussed. Both top-down and bottom-up codes were used to analyse the focus groups. Professionals ascribed three roles to the CSC: 1) broker role, 2) referral, 3) facilitator. Professionals were enthusiastic about how the current connection was established. However, barriers relating to their own sector were currently hindering the connection: primary care professionals' lack of time, money and knowledge, and the lack of suitable PA activities and instructors for the target group. This study provides further insight into the CSC role and the connection between the sectors from the point of view of primary care, welfare, and sport professionals. Professionals found the CSC role promising, but barriers are currently hindering the collaboration between both sectors. More time for the CSC and changes in the way the primary care and PA sector are organized seem to be necessary to overcome the identified barriers and to make a success of the connection. Dutch Trial register NTR4986 . Registered 14 December 2014.

Cognitive spare capacity: evaluation data and its association with comprehension of dynamic conversations

PubMed Central

Keidser, Gitte; Best, Virginia; Freeston, Katrina; Boyce, Alexandra

2015-01-01

It is well-established that communication involves the working memory system, which becomes increasingly engaged in understanding speech as the input signal degrades. The more resources allocated to recovering a degraded input signal, the fewer resources, referred to as cognitive spare capacity (CSC), remain for higher-level processing of speech. Using simulated natural listening environments, the aims of this paper were to (1) evaluate an English version of a recently introduced auditory test to measure CSC that targets the updating process of the executive function, (2) investigate if the test predicts speech comprehension better than the reading span test (RST) commonly used to measure working memory capacity, and (3) determine if the test is sensitive to increasing the number of attended locations during listening. In Experiment I, the CSC test was presented using a male and a female talker, in quiet and in spatially separated babble- and cafeteria-noises, in an audio-only and in an audio-visual mode. Data collected on 21 listeners with normal and impaired hearing confirmed that the English version of the CSC test is sensitive to population group, noise condition, and clarity of speech, but not presentation modality. In Experiment II, performance by 27 normal-hearing listeners on a novel speech comprehension test presented in noise was significantly associated with working memory capacity, but not with CSC. Moreover, this group showed no significant difference in CSC as the number of talker locations in the test increased. There was no consistent association between the CSC test and the RST. It is recommended that future studies investigate the psychometric properties of the CSC test, and examine its sensitivity to the complexity of the listening environment in participants with both normal and impaired hearing. PMID:25999904

The Role of Biomaterials on Cancer Stem Cell Enrichment and Behavior

NASA Astrophysics Data System (ADS)

Ordikhani, Faride; Kim, Yonghyun; Zustiak, Silviya P.

2015-11-01

The theory of cancer stem cells (CSCs) and their role in cancer metastasis, tumorigenicity and resistance to therapy is slowly shifting the emphasis on the search for cancer cure: more evidence is surfacing that a successful therapy should be geared against this rare cancer cell population. Unfortunately, CSCs are difficult to culture in vitro which severely limits the progress of CSC research. This review gives a brief overview of CSCs and their microenvironment, with particular focus on studies that used in vitro biomaterial-based models and biomaterial/CSC interfaces for the enrichment of CSCs. Biomaterial properties relevant to CSC behaviors are also addressed. While the discussed research field is still in its infancy, it appears that in vitro cancer models that include a biomaterial can support CSC enrichment and this has proved indispensable to the study of their biology as well as the development of novel cancer therapies.

Assessing stemness and proliferation properties of the newly established colon cancer 'stem' cell line, CSC480 and novel approaches to identify dormant cancer cells.

PubMed

Alowaidi, Faisal; Hashimi, Saeed Mujahid; Alqurashi, Naif; Alhulais, Reem; Ivanovski, Saso; Bellette, Bernadette; Meedenyia, Adrian; Lam, Alfred; Wood, Stephen

2018-06-01

To date two questions that remain unanswered regarding cancer are the following: i) how is it initiated, and ii) what is the role that cancer stem cells (CSCs) play in the disease process? Understanding the biology of CSCs and how they are generated is pivotal for the development of successful treatment regimens. To date, the lack of a representative cell model has prevented the successful identification and eradication of CSCs in vivo. The current methods of CSC identification are dependent on the protocol used to generate these cells, which has introduced variation and made the identification process more complicated. Furthermore, the list of possible markers is increasing in complexity. This is further confounded by the fact that there is insufficient information to determine whether the cells these markers detect are truly self‑renewing stem cells or, instead, progenitor cells. In the present study, we investigated a novel cell line model, CSC480, which can be employed to assess CSC markers and for testing novel therapeutic regimens. CSC480 cells have been revealed to express markers of CSCs such as CD44, ALDH1 and Sox2, that have lower expression in the SW480 cell line. CSC480 cells also expressed higher levels of the cancer resistance marker, ABCG2 and had higher proliferative and growth capacity than SW480 cells. In the present study, we also evaluated a novel approach to identify different cell types present in heterogeneous cancer cell populations according to their proliferative ability using the proliferation marker 5‑ethynyl‑2'‑deoxyuridine (EdU). Furthermore, using EdU, we identified dormant cells with a modified label‑retaining cell (LRC) protocol. Through this novel LRC method, we assessed newly discovered markers of stemness to ascertain their capability to identify quiescent from dividing CSCs. In conclusion, the CSC480 cell line was an important model to be used in unravelling the underlying mechanisms that control fast‑dividing and partially self‑renewing stem cells (SCs) that may give rise to cancer.

Restoration of outer segments of foveal photoreceptors after resolution of central serous chorioretinopathy.

PubMed

Ojima, Yumiko; Tsujikawa, Akitaka; Yamashiro, Kenji; Ooto, Sotaro; Tamura, Hiroshi; Yoshimura, Nagahisa

2010-01-01

To study morphologically and functionally the prognosis of damaged outer segments of the foveal photoreceptor layer in eyes with resolved central serous chorioretinopathy (CSC). We studied retrospectively the medical records of 70 patients (74 eyes) with resolved CSC. Optical coherence tomography was used to detect the junctions between inner and outer segments of the photoreceptors (IS/OS) as a hallmark of the integrity of the outer photoreceptor layer. In 53 eyes (71.6%), the IS/OS line was clearly detected beneath the fovea immediately after resolution of the retinal detachment, with good visual acuity (VA). In the remaining 21 eyes (28.4%), however, the foveal IS/OS line could not be detected shortly after resolution of CSC, and VA was variable, ranging from 0.1 to 1.5 (median, 0.9). Of these 21 eyes, 15 had a follow-up examination with OCT, and in four the foveal IS/OS line was not detected at the follow-up and vision in these eyes remained poor. However, nine eyes showed recovery of the foveal IS/OS line during follow-up, and these eyes had substantial visual recovery. Immediately after resolution of active CSC, although the IS/OS line cannot be detected beneath the fovea, it often shows restoration over time, with visual recovery, though in some eyes no restoration takes place and the prognosis remains poor.

Resistance to Cell Death and Its Modulation in Cancer Stem Cells

PubMed Central

Safa, Ahmad R.

2017-01-01

Accumulating evidence has demonstrated that human cancers arise from various tissues of origin that initiate from cancer stem cells (CSCs) or cancer-initiating cells. The extrinsic and intrinsic apoptotic pathways are dysregulated in CSCs, and these cells play crucial roles in tumor initiation, progression, cell death resistance, chemo- and radiotherapy resistance, and tumor recurrence. Understanding CSC-specific signaling proteins and pathways is necessary to identify specific therapeutic targets that may lead to the development of more efficient therapies selectively targeting CSCs. Several signaling pathways—including the phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR), maternal embryonic leucine zipper kinase (MELK), NOTCH1, and Wnt/β-catenin—and expression of the CSC markers CD133, CD24, CD44, Oct4, Sox2, Nanog, and ALDH1A1 maintain CSC properties. Studying such pathways may help to understand CSC biology and lead to the development of potential therapeutic interventions to render CSCs more sensitive to cell death triggered by chemotherapy and radiation therapy. Moreover, recent demonstrations of dedifferentiation of differentiated cancer cells into CSC-like cells have created significant complexity in the CSCs hypothesis. Therefore, any successful therapeutic agent or combination of drugs for cancer therapy must eliminate not only CSCs but differentiated cancer cells and the entire bulk of tumor cells. This review article expands on the CSC hypothesis and paradigm with respect to major signaling pathways and effectors that regulate CSC apoptosis resistance. Moreover, selective CSC apoptotic modulators and their therapeutic potential for making tumors more responsive to therapy are discussed. The use of novel therapies, including small-molecule inhibitors of specific proteins in signaling pathways that regulate stemness, proliferation and migration of CSCs, immunotherapy, and noncoding microRNAs may provide better means of treating CSCs. PMID:27915972

Cell plasticity and heterogeneity in cancer.

PubMed

Marjanovic, Nemanja D; Weinberg, Robert A; Chaffer, Christine L

2013-01-01

Heterogeneity within a given cancer arises from diverse cell types recruited to the tumor and from genetic and/or epigenetic differences amongst the cancer cells themselves. These factors conspire to create a disease with various phenotypes. There are 2 established models of cancer development and progression to metastatic disease. These are the clonal evolution and cancer stem cell models. The clonal evolution theory suggests that successive mutations accumulating in a given cell generate clonal outgrowths that thrive in response to microenvironmental selection pressures, dictating the phenotype of the tumor. The alternative cancer stem cell (CSC) model suggests that cancer cells with similar genetic backgrounds can be hierarchically organized according to their tumorigenic potential. Accordingly, CSCs reside at the apex of the hierarchy and are thought to possess the majority of a cancer's tumor-initiating and metastatic ability. A defining feature of this model is its apparent unidirectional nature, whereby CSCs undergo symmetric division to replenish the CSC pool and irreversible asymmetric division to generate daughter cells (non-CSCs) with low tumorigenic potential. However, evolving evidence supports a new model of tumorigenicity, in which considerable plasticity exists between the non-CSC and CSC compartments, such that non-CSCs can reacquire a CSC phenotype. These findings suggest that some tumors may adhere to a plastic CSC model, in which bidirectional conversions are common and essential components of tumorigenicity. Accumulating evidence surrounding the plasticity of cancer cells, in particular, suggests that aggressive CSCs can be created de novo within a tumor. Given the current focus on therapeutic targeting of CSCs, we discuss the implications of non-CSC-to-CSC conversions on the development of future therapies. © 2012 American Association for Clinical Chemistry

Building non-traditional collaborations to innovatively address climate-related scientific and management needs

NASA Astrophysics Data System (ADS)

Bamzai, A.; Mcpherson, R. A.

2014-12-01

The South Central Climate Science Center (SC-CSC) is one of eight regional centers formed by the U.S. Department of the Interior in order to provide decision makers with the science, tools, and information they need to address the impacts of climate variability and change on their areas of responsibility. The SC-CSC is operated through the U.S. Geological Survey, in partnership with a consortium led by the University of Oklahoma that also includes Texas Tech University, Oklahoma State University, Louisiana State University, the Chickasaw Nation, the Choctaw Nation of Oklahoma, and NOAA's Geophysical Fluid Dynamics Lab (GFDL). The SC-CSC is distinct from all other CSCs in that we have strategically included non-traditional collaborators directly within our governing consortium. The SC-CSC is the only CSC to include any Tribal nations amongst our consortium (the Chickasaw Nation and the Choctaw Nation of Oklahoma) and to employ a full-time tribal liaison. As a result and in partnership with Tribes, we are able to identify the unique challenges that the almost 70 federally recognized Tribes within our region face. We also can develop culturally sensitive research projects or outreach efforts that bridge western science and traditional knowledge to address their needs. In addition, the SC-CSC is the only CSC to include another federal institution (GFDL) amongst our consortium membership. GFDL is a world-leader in climate modeling and model interpretation. Partnering GFDL's expertise in the evaluation of climate models and downscaling methods with the SC-CSC's stakeholder-driven approach allows for the generation and dissemination of guidance documents and training to accompany the high quality datasets already in development. This presentation will highlight the success stories and co-benefits of the SC-CSC's collaborations with Tribal nations and with GFDL, as well as include information on how other partners can connect to our ongoing efforts.

The Warburg effect version 2.0

PubMed Central

Menendez, Javier A.; Joven, Jorge; Cufí, Sílvia; Corominas-Faja, Bruna; Oliveras-Ferraros, Cristina; Cuyàs, Elisabet; Martin-Castillo, Begoña; López-Bonet, Eugeni; Alarcón, Tomás; Vazquez-Martin, Alejandro

2013-01-01

When fighting cancer, knowledge on metabolism has always been important. Today, it matters more than ever. The restricted cataloging of cancer genomes is quite unlikely to achieve the task of curing cancer, unless it is integrated into metabolic networks that respond to and influence the constantly evolving cancer stem cell (CSC) cellular states. Once the genomic era of carcinogenesis had pushed the 1920s Otto Warburg’s metabolic cancer hypothesis into obscurity for decades, the most recent studies begin to support a new developing paradigm, in which the molecular logic behind the conversion of non-CSCs into CSCs can be better understood in terms of the “metabolic facilitators” and “metabolic impediments” that operate as proximate openings and roadblocks, respectively, for the transcriptional events and signal transduction programs that ultimately orchestrate the intrinsic and/or microenvironmental paths to CSC cellular states. Here we propose that a profound understanding of how human carcinomas install a proper “Warburg effect version 2.0” allowing them to “run” the CSCs’ “software” programs should guide a new era of metabolo-genomic-personalized cancer medicine. By viewing metabolic reprogramming of CSCs as an essential characteristic that allows dynamic, multidimensional and evolving cancer populations to compete successfully for their expansion on the organism, we now argue that CSCs bioenergetics might be another cancer hallmark. A definitive understanding of metabolic reprogramming in CSCs may complement or to some extent replace, the 30-y-old paradigm of targeting oncogenes to treat human carcinomas, because it can be possible to metabolically create non-permissive or “hostile” metabotypes to prevent the occurrence of CSC cellular states with tumor- and metastasis-initiating capacity. PMID:23549172

Structural and electronic studies of metal carbide clusterfullerene Sc2C2@Cs-C72

NASA Astrophysics Data System (ADS)

Feng, Yongqiang; Wang, Taishan; Wu, Jingyi; Feng, Lai; Xiang, Junfeng; Ma, Yihan; Zhang, Zhuxia; Jiang, Li; Shu, Chunying; Wang, Chunru

2013-07-01

We present a metal carbide clusterfullerene Sc2C2@Cs(10528)-C72, whose structure has been baffling for many years. A motional endohedral Sc2C2 cluster, special molecule geometry and electronic structure were found in Sc2C2@Cs(10528)-C72. The paramagnetic Sc2C2@Cs-C72 anion radical was successfully prepared by a chemical reduction method and hyperfine couplings in the ESR spectrum were observed.We present a metal carbide clusterfullerene Sc2C2@Cs(10528)-C72, whose structure has been baffling for many years. A motional endohedral Sc2C2 cluster, special molecule geometry and electronic structure were found in Sc2C2@Cs(10528)-C72. The paramagnetic Sc2C2@Cs-C72 anion radical was successfully prepared by a chemical reduction method and hyperfine couplings in the ESR spectrum were observed. Electronic supplementary information (ESI) available: Experimental details, HPLC chromatogram, and DFT calculations. CCDC 917712. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c3nr01739g

The Complexities of Implementing Cluster Supply Chain - Case Study of JCH

NASA Astrophysics Data System (ADS)

Xue, Xiao; Zhang, Jibiao; Wang, Yang

As a new type of management pattern, "cluster supply chain" (CSC) can help SMEs to face the global challenges through all kinds of collaboration. However, a major challenge in implementing CSC is the gap between theory and practice in the field. In an effort to provide a better understanding of this emerging phenomenon, this paper presents the implementation process of CSC in the context of JingCheng Mechanical & Electrical Holding co., ltd.(JCH) as a case study. The cast study of JCH suggests that the key problems in the practice of cluster supply chain: How do small firms use cluster supply chain? Only after we clarify the problem, the actual construction and operation of cluster supply chain does show successful results as it should be.

The Wnt/β-catenin signaling/Id2 cascade mediates the effects of hypoxia on the hierarchy of colorectal-cancer stem cells.

PubMed

Dong, Hye-Jin; Jang, Gyu-Beom; Lee, Hwa-Yong; Park, Se-Ra; Kim, Ji-Young; Nam, Jeong-Seok; Hong, In-Sun

2016-03-11

Hypoxia, a feature common to most solid tumors, is known to regulate many aspects of tumorigenesis. Recently, it was suggested that hypoxia increased the size of the cancer stem-cell (CSC) subpopulations and promoted the acquisition of a CSC-like phenotype. However, candidate hypoxia-regulated mediators specifically relevant to the stemness-related functions of colorectal CSCs have not been examined in detail. In the present study, we showed that hypoxia specifically promoted the self-renewal potential of CSCs. Through various in vitro studies, we found that hypoxia-induced Wnt/β-catenin signaling increased the occurrence of CSC-like phenotypes and the level of Id2 expression in colorectal-cancer cells. Importantly, the levels of hypoxia-induced CSC-sphere formation and Id2 expression were successfully attenuated by treatment with a Wnt/β-catenin-signaling inhibitor. We further demonstrated, for the first time, that the degree of hypoxia-induced CSC-sphere formation (CD44(+) subpopulation) in vitro and of tumor metastasis/dissemination in vivo were markedly suppressed by knocking down Id2 expression. Taken together, these data suggested that Wnt/β-catenin signaling mediated the hypoxia-induced self-renewal potential of colorectal-cancer CSCs through reactivating Id2 expression.

Center for Space Construction

NASA Technical Reports Server (NTRS)

Su, Renjeng

1998-01-01

The Center for Space Construction (CSC) at University of Colorado at Boulder is one of eight University Space Engineering Research Centers established by NASA in 1988. The mission of the Center is to conduct research into space technology and to directly contribute to space engineering education. The Center reports to the Department of Aerospace Engineering Sciences and resides in the College of Engineering and Applied Sciences. The College has a long and successful track record of cultivating multi-disciplinary research and education programs. The Center for Space Construction represents prominent evidence of this record. The basic concept on which the Center was founded is the in-space construction of large space systems, such as space stations, interplanetary space vehicles, and extraterrestrial space structures. Since 1993, the scope of CSC research has evolved to include the design and construction of all spacecraft, large and small. With the broadened scope our research projects seek to impact the technological basis for spacecraft such as remote sensing satellites, communication satellites and other special-purpose spacecraft, as well as large space platforms. A summary of accomplishments, including student participation and degrees awarded, during the contract period is presented.

78 FR 39251 - 21st Century Conservation Service Corps Partnership Opportunity

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-01

.... Background The 21CSC is a bold national effort to put America's youth and veterans to work protecting, restoring, and enhancing America's Great Outdoors. Recognizing the need for job opportunities for youth and... America's Great Outdoors Council, formed a Federal Advisory Committee (FACA) to develop recommendations...

Lipidomics of tobacco leaf and cigarette smoke.

PubMed

Dunkle, Melissa N; Yoshimura, Yuta; T Kindt, Ruben; Ortiz, Alexia; Masugi, Eri; Mitsui, Kazuhisa; David, Frank; Sandra, Pat; Sandra, Koen

2016-03-25

Detailed lipidomics experiments were performed on the extracts of cured tobacco leaf and of cigarette smoke condensate (CSC) using high-resolution liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (LC-Q-TOF MS). Following automated solid-phase extraction (SPE) fractionation of the lipid extracts, over 350 lipids could be annotated. From a large-scale study on 22 different leaf samples, it was determined that differentiation based on curing type was possible for both the tobacco leaf and the CSC extracts. Lipids responsible for the classification were identified and the findings were correlated to proteomics data acquired from the same tobacco leaf samples. Prediction models were constructed based on the lipid profiles observed in the 22 leaf samples and successfully allowed for curing type classification of new tobacco leaves. A comparison of the leaf and CSC data provided insight into the lipidome changes that occur during the smoking process. It was determined that lipids which survive the smoking process retain the same curing type trends in both the tobacco leaf and CSC data. Copyright © 2015 Elsevier B.V. All rights reserved.

CSC Tip Sheets: Working with Institutional Partners

EPA Pesticide Factsheets

Partner with organizations, such as other jurisdictions, utilities, complementary programs, community-based organizations, and others, can help you implement your program and achieve your collective goals.

Comparison of Provider Types Who Performed Prehospital Lifesaving Interventions: A Prospective Study

DTIC Science & Technology

2014-12-01

In less than 2 hours, 15 critically ill children were triaged and admitted to the PICU or surge spaces. Conclusions:Identified strengths included...details increasing telemedicine uti - lization during a 4 year period and outlines program structural changes that improved utilization. Methods: The study...population survival. CSC ICU resource- allocation algorithms (ALGs) exist for adults. Our goal was to evaluate a CSC pandemic ALG for children . Methods

Self-Renewal and CSCs In Vitro Enrichment: Growth as Floating Spheres

PubMed Central

Mehta, Pooja; Novak, Caymen; Raghavan, Shreya; Ward, Maria; Mehta, Geeta

2018-01-01

Cancer stem cells (CSC) are a vital component to the progression and reoccurrence of cancers, making them a primary target of study for both fundamental understanding of cancer biology and the development of effective and targeted treatments. CSCs reside in a complex 3D microenvironment, and the 3D spheroids are an indispensable tool in tumor biology due to their 3D structure and replication of the tumor microenvironment. Within this chapter the methodology for CSC isolation, suspension culture in hanging drop model, and characterization assays for CSC are described. First, the methodology for identifying and isolating CSCs from patient tumors, ascites, or cancer cell lines is described through the use of FACS analysis. Next, a detailed description of 3D hanging drop model for generating CSC spheroids is provided, followed by maintenance and monitoring techniques for extended 3D culture. Analysis methods are described for the quantification of CSC spheroid proliferation and viability tracking, throughout culture by on-plate alamarBlue fluorescence. Additional viability assays are described utilizing confocal microscopy with Live/Dead Viability/Cytotoxicity Kit. The characterization of CSCs populations within spheroids is described through FACS analysis. Further, an immunohistochemistry procedure is described for cell-cell and cell-matrix interaction assessment. Finally, several notes and tips for successful experiments with 3D CSC spheroids on the hanging drop model are provided. These methods are not only applicable to CSCs within a variety of tumor cell types, for not only understanding the fundamental tumor biology, but also for drug screening and development of preclinical chemotherapeutic strategies. PMID:28986887

CSC Tip Sheets: Working with Corporations

EPA Pesticide Factsheets

Programs can work with corporations to reduce companies’ greenhouse gas emissions and energy use, as well as create partnerships to reach employees and the community with local sustainability program offerings.

Rapid assessment of cataract surgical coverage in rural Zululand.

PubMed

Rotchford, A P; Johnson, G J

2000-10-01

Cataract surgical coverage (CSC) is a useful indicator of the degree of success of a cataract intervention programme. However, because previously described methods are time-consuming and labour-intensive, they are rarely performed. This study describes a simple and inexpensive assessment of CSC based on screening of pensioners at pension delivery sites in a rural district. Random cluster-based cross-sectional survey. State pension distribution sites in Hlabisa, a rural district in KwaZulu-Natal, South Africa. 562 old-age pensioners. Subjects found to be blind (visual acuity < 3/60) and those reporting a history of eye surgery were examined using a torch and direct ophthalmoscope by an ophthalmologist. Cases of blindness due to operable cataract and post-cataract surgical subjects were identified. CSC was found to be 38.5% (95% confidence interval 29.1-47.9%). Blindness prevalence was 10.3%, with 69.0% due to cataract.

Comparing half-dose photodynamic therapy with high-density subthreshold micropulse laser treatment in patients with chronic central serous chorioretinopathy (the PLACE trial): study protocol for a randomized controlled trial.

PubMed

Breukink, Myrte B; Downes, Susan M; Querques, Giuseppe; van Dijk, Elon H C; den Hollander, Anneke I; Blanco-Garavito, Rocio; Keunen, Jan E E; Souied, Eric H; MacLaren, Robert E; Hoyng, Carel B; Fauser, Sascha; Boon, Camiel J F

2015-09-21

Chronic central serous chorioretinopathy (cCSC) is an eye disease characterized by an accumulation of serous fluid under the retina. It is postulated that this fluid accumulation results from hyperpermeability and swelling of the choroid, the underlying vascular tissue of the eye, causing a dysfunction of the retinal pigment epithelium. This fluid accumulation causes neuroretinal detachment. A prolonged neuroretinal detachment in the macula can lead to permanent vision loss. Therefore, treatment is aimed primarily at achieving resolution of subretinal fluid, preferably within the first 4 months after diagnosis of the disease. A broad spectrum of treatment modalities has been investigated in cCSC, but no consensus exists on the optimal treatment of cCSC. Currently, photodynamic therapy (PDT) and high-density subthreshold micropulse laser treatment (HSML) are among the most frequently cited treatments in obtaining successful neuroretinal reattachment. This is a randomized, controlled, open-label, multicenter trial comparing the efficacy of half-dose PDT to HSML in treating patients with cCSC. A total of 156 patients will be recruited, 78 patients in each treatment arm, with a maximum follow-up duration of 8 months after the first treatment. A complete ophthalmological examination with vision-related quality of life (NEI VFQ-25) and stress questionnaires, will be performed at baseline, 6 to 8 weeks after the first treatment, 6 to 8 weeks after a second treatment (if necessary), and at the final follow-up visit at 7 to 8 months after the first treatment. Treatment visits will be scheduled within 3 weeks after the baseline visit, and within 3 weeks after the first control visit, if a second treatment is required. Both half-dose PDT and HSML may be effective treatments in cCSC, but because of the lack of prospective randomized controlled trials, which treatment should be the first choice remains unclear. The aim of this study is to compare the efficacy of half-dose PDT to HSML. The primary endpoint to evaluate efficacy will be a complete absence of subretinal fluid on optical coherence tomography after treatment. Secondary functional endpoints include change in Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity, retinal sensitivity on microperimetry, and NEI VFQ-25 questionnaire of visual functioning. Registration number Institutional Review Board (CMO Arnhem-Nijmegen, the Netherlands): 2013/203 NL nr.: 41266.091.13 TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01797861 . Date of registration: 21 February 2013.

Physiological and hypoxic oxygen concentration differentially regulates human c-Kit+ cardiac stem cell proliferation and migration.

PubMed

Bellio, Michael A; Rodrigues, Claudia O; Landin, Ana Marie; Hatzistergos, Konstantinos E; Kuznetsov, Jeffim; Florea, Victoria; Valasaki, Krystalenia; Khan, Aisha; Hare, Joshua M; Schulman, Ivonne Hernandez

2016-12-01

Cardiac stem cells (CSCs) are being evaluated for their efficacy in the treatment of heart failure. However, numerous factors impair the exogenously delivered cells' regenerative capabilities. Hypoxia is one stress that contributes to inadequate tissue repair. Here, we tested the hypothesis that hypoxia impairs cell proliferation, survival, and migration of human CSCs relative to physiological and room air oxygen concentrations. Human endomyocardial biopsy-derived CSCs were isolated, selected for c-Kit expression, and expanded in vitro at room air (21% O 2 ). To assess the effect on proliferation, survival, and migration, CSCs were transferred to physiological (5%) or hypoxic (0.5%) O 2 concentrations. Physiological O 2 levels increased proliferation (P < 0.05) but did not affect survival of CSCs. Although similar growth rates were observed in room air and hypoxia, a significant reduction of β-galactosidase activity (-4,203 fluorescent units, P < 0.05), p16 protein expression (0.58-fold, P < 0.001), and mitochondrial content (0.18-fold, P < 0.001) in hypoxia suggests that transition from high (21%) to low (0.5%) O 2 reduces senescence and promotes quiescence. Furthermore, physiological O 2 levels increased migration (P < 0.05) compared with room air and hypoxia, and treatment with mesenchymal stem cell-conditioned media rescued CSC migration under hypoxia to levels comparable to physiological O 2 migration (2-fold, P < 0.05 relative to CSC media control). Our finding that physiological O 2 concentration is optimal for in vitro parameters of CSC biology suggests that standard room air may diminish cell regenerative potential. This study provides novel insights into the modulatory effects of O 2 concentration on CSC biology and has important implications for refining stem cell therapies. Copyright © 2016 the American Physiological Society.

Nucleolin overexpression in breast cancer cell sub-populations with different stem-like phenotype enables targeted intracellular delivery of synergistic drug combination.

PubMed

Fonseca, Nuno A; Rodrigues, Ana S; Rodrigues-Santos, Paulo; Alves, Vera; Gregório, Ana C; Valério-Fernandes, Ângela; Gomes-da-Silva, Lígia C; Rosa, Manuel Santos; Moura, Vera; Ramalho-Santos, João; Simões, Sérgio; Moreira, João Nuno

2015-11-01

Breast cancer stem cells (CSC) are thought responsible for tumor growth and relapse, metastization and active evasion to standard chemotherapy. The recognition that CSC may originate from non-stem cancer cells (non-SCC) through plastic epithelial-to-mesenchymal transition turned these into relevant cell targets. Of crucial importance for successful therapeutic intervention is the identification of surface receptors overexpressed in both CSC and non-SCC. Cell surface nucleolin has been described as overexpressed in cancer cells as well as a tumor angiogenic marker. Herein we have addressed the questions on whether nucleolin was a common receptor among breast CSC and non-SCC and whether it could be exploited for targeting purposes. Liposomes functionalized with the nucleolin-binding F3 peptide, targeted simultaneously, nucleolin-overexpressing putative breast CSC and non-SCC, which was paralleled by OCT4 and NANOG mRNA levels in cells from triple negative breast cancer (TNBC) origin. In murine embryonic stem cells, both nucleolin mRNA levels and F3 peptide-targeted liposomes cellular association were dependent on the stemness status. An in vivo tumorigenic assay suggested that surface nucleolin overexpression per se, could be associated with the identification of highly tumorigenic TNBC cells. This proposed link between nucleolin expression and the stem-like phenotype in TNBC, enabled 100% cell death mediated by F3 peptide-targeted synergistic drug combination, suggesting the potential to abrogate the plasticity and adaptability associated with CSC and non-SCC. Ultimately, nucleolin-specific therapeutic tools capable of simultaneous debulk multiple cellular compartments of the tumor microenvironment may pave the way towards a specific treatment for TNBC patient care. Copyright © 2015 Elsevier Ltd. All rights reserved.

Corneo-scleral contact lenses in an uncommon case of keratoconus with high hyperopia and astigmatism.

PubMed

Porcar, Esteban; Montalt, Juan Carlos; España-Gregori, Enrique; Peris-Martínez, Cristina

2017-10-01

To analyse the visual quality achieved by fitting corneo-scleral contact lenses (CScL) in an uncommon case of bilateral keratoconus, high hyperopia and astigmatism. A 45-year-old man presented for eye examination due to the unsatisfactory quality of his vision wearing soft toric contact lenses. He presented high hyperopia and astigmatism with bilateral keratoconus. He was fitted with CScL to correct his irregular astigmatism and ocular aberrations. A diagnostic trial set was used in the fitting process and he was assessed according to standardised fitting methodology. Visual acuity, corneal topography, biometry and ocular aberrations were evaluated. The follow-up period was 1year. The best spectacle-corrected visual acuity was 20/32 with +8.00/-4.50×30° for the right eye (RE) and 20/25 with +7.75/-2.25×120° for the left eye (LE). After CScL fitting, visual acuity was improved to 20/20 and 20/16 for the RE and LE, respectively. The patient wore these contact lenses an average of 13h a day. The total high order aberrations decreased by approximately 79% in the RE (2.37-0.50μm) and 47% in the LE (1.04-0.55μm) after CScL fitting. Visual quality and wearing time were maintained after 1year wearing CScL. In addition, no adverse ocular effects were found during this period. The present case report describes how the patient had CScL fitted successfully for management of keratoconus with high hyperopia and astigmatism. They provided optimal visual quality, along with prolonged use times and no adverse effects to the cornea. Copyright © 2017 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.

Cooperatively surrounding control for multiple Euler-Lagrange systems subjected to uncertain dynamics and input constraints

NASA Astrophysics Data System (ADS)

Chen, Liang-Ming; Lv, Yue-Yong; Li, Chuan-Jiang; Ma, Guang-Fu

2016-12-01

In this paper, we investigate cooperatively surrounding control (CSC) of multi-agent systems modeled by Euler-Lagrange (EL) equations under a directed graph. With the consideration of the uncertain dynamics in an EL system, a backstepping CSC algorithm combined with neural-networks is proposed first such that the agents can move cooperatively to surround the stationary target. Then, a command filtered backstepping CSC algorithm is further proposed to deal with the constraints on control input and the absence of neighbors’ velocity information. Numerical examples of eight satellites surrounding one space target illustrate the effectiveness of the theoretical results. Project supported by the National Basic Research Program of China (Grant No. 2012CB720000) and the National Natural Science Foundation of China (Grant Nos. 61304005 and 61403103).

The Foreign Area Officer Program. Volume I. The Role of the Military Advisor

DTIC Science & Technology

1973-05-01

attended the MAPA or MAO C&SC, and are not MAOP members. Some of these positions are advisory posi- tions. For purposes of this report, we did not...determine whether there is a comparable problem at the MAAG end--i.e. , requisitioning MAPA or MAO C&SC graduates and not getting them—or to what...U. S. Army training in advisor functions and roles is incorporated in the Military Assistance Programmer/Advisor ( MAPA ) and Military Assistance

Cigarette smoke condensate induces differential expression and promoter methylation profiles of critical genes involved in lung cancer in NL-20 lung cells in vitro: short-term and chronic exposure.

PubMed

Word, Beverly; Lyn-Cook, Lascelles E; Mwamba, Bibi; Wang, Honggang; Lyn-Cook, Beverly; Hammons, George

2013-01-01

Establishing early diagnostic markers of harm is critical for effective prevention programs and regulation of tobacco products. This study examined effects of cigarette smoke condensate (CSC) on expression and promoter methylation profile of critical genes (DAPK, ECAD, MGMT, and RASSF1A) involved in lung cancer development in different human lung cell lines. NL-20 cells were treated with 0.1-100 μg/ml of CSC for 24 to 72 hrs for short-term exposures. DAPK expression or methylation status was not significantly affected. However, CSC treatment resulted in changes in expression and promoter methylation profile of ECAD, MGMT, and RASSF1A. For chronic studies, cells were exposed to 1 or 10 μg/ml CSC up to 28 days. Cells showed morphological changes associated with transformation and changes in invasion capacities and global methylation status. This study provides critical data suggesting that epigenetic changes could serve as an early biomarker of harm due to exposure to cigarette smoke.

CSC Tip Sheets: Testimonial Videos

EPA Pesticide Factsheets

Testimonial videos can be used to communicate to your target audience from the perspective of someone like them who has participated in program activities and can speak to the benefits and motivations of the activities your program is promoting.

The development of a malignant tumor is due to a desperate asexual self-cloning process in which cancer stem cells develop the ability to mimic the genetic program of germline cells

PubMed Central

Vinnitsky, Vladimir

2014-01-01

To date there is no explanation why the development of almost all types of solid tumors occurs sharing a similar scenario: (1) creation of a cancer stem cell (CSC), (2) CSC multiplication and formation of a multicellular tumor spheroid (TS), (3) vascularization of the TS and its transformation into a vascularized primary tumor, (4) metastatic spreading of CSCs, (5) formation of a metastatic TSs and its transformation into metastatic tumors, and (6) potentially endless repetition of this cycle of events. The above gaps in our knowledge are related to the biology of cancer and specifically to tumorigenesis, which covers the process from the creation of a CSC to the formation of a malignant tumor and the development of metastases. My Oncogerminative Theory of Tumorigenesis considers tumor formation as a dynamic self-organizing process that mimics a self-organizing process of early embryo development. In the initial step in that process, gene mutations combined with epigenetic dysregulation cause somatic cells to be reprogrammed into CSCs, which are immortal pseudo-germline cells. Mimicking the behavior of fertilized germline cells, the CSC achieves immortality by passing through the stages of its life-cycle and developing into a pseudo-blastula-stage embryo, which manifests in the body as a malignant tumor. In this view, the development of a malignant tumor from a CSC is a phenomenon of developmental biology, which we named a desperate asexual self-cloning event. The theory explains seven core characteristics of malignant tumors: (1) CSC immortality, (2) multistep development of a malignant tumor from a single CSC, (3) heterogeneity of malignant tumor cell populations, (4) metastatic spread of CSCs, (5) invasive growth, (6) malignant progression, and (7) selective immune tolerance toward cancer cells. The Oncogerminative Theory of Tumorigenesis suggests new avenues for discovery of revolutionary therapies to treat, prevent, and eradicate cancer. PMID:28232878

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

Mohapatra, Purusottam; Satapathy, Shakti Ranjan; Das, Dipon

Cigarette smoking is a key factor for the development and progression of different cancers including mammary tumor in women. Resveratrol (Res) is a promising natural chemotherapeutic agent that regulates many cellular targets including p21, a cip/kip family of cyclin kinase inhibitors involved in DNA damage-induced cell cycle arrest and blocking of DNA replication and repair. We have recently shown that cigarette smoke condensate (CSC) prepared from commercially available Indian cigarette can cause neoplastic transformation of normal breast epithelial MCF-10A cell. Here we studied the mechanism of Res mediated apoptosis in CSC transformed (MCF-10A-Tr) cells in vitro and in vivo. Resmore » mediated apoptosis in MCF-10A-Tr cells was a p21 dependent event. It increased the p21 protein expression in MCF-10A-Tr cells and MCF-10A-Tr cells-mediated tumors in xenograft mice. Res treatment reduced the tumor size(s) and expression of anti-apoptotic proteins (e.g. PI3K, AKT, NFκB) in solid tumor. The expressions of cell cycle regulatory (Cyclins, CDC-2, CDC-6, etc.), BER associated (Pol-β, Pol-δ, Pol-ε, Pol-η, RPA, Fen-1, DNA-Ligase-I, etc.) proteins and LP-BER activity decreased in MCF-10A-Tr cells but remain significantly unaltered in isogenic p21 null MCF-10A-Tr cells after Res treatment. Interestingly, no significant changes were noted in SP-BER activity in both the cell lines after Res exposure. Finally, it was observed that increased p21 blocks the LP-BER in MCF-10A-Tr cells by increasing its interaction with PCNA via competing with Fen-1 after Res treatment. Thus, Res caused apoptosis in CSC-induced cancer cells by reduction of LP-BER activity and this phenomenon largely depends on p21. - Highlights: • Resveratrol (Res) caused reduction of MCF-10A-Tr cell growth by inducing apoptosis. • Res caused cell cycle arrest and DNA damage in p21 dependent manner. • Res mediated LP-BER reduction in MCF-10A-Tr cells was a p21 dependent phenomenon. • Res inhibits BER and PI3K, AKT, and NFκB protein expressions in tumor and xenografts. • Res-induced-p21 inhibited DNA repair by modulating Fen-1 binding to PCNA complex.« less

76 FR 32980 - Telecommunications Service Priority (TSP) System

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-07

... of Cybersecurity and Communications (CS&C), National Communications System (NCS), will submit the... Protection and Programs Directorate, Office of Cybersecurity and Communications, National Communications...

Pancreatic cancer stem cell markers and exosomes - the incentive push

PubMed Central

Heiler, Sarah; Wang, Zhe; Zöller, Margot

2016-01-01

Pancreatic cancer (PaCa) has the highest death rate and incidence is increasing. Poor prognosis is due to late diagnosis and early metastatic spread, which is ascribed to a minor population of so called cancer stem cells (CSC) within the mass of the primary tumor. CSC are defined by biological features, which they share with adult stem cells like longevity, rare cell division, the capacity for self renewal, differentiation, drug resistance and the requirement for a niche. CSC can also be identified by sets of markers, which for pancreatic CSC (Pa-CSC) include CD44v6, c-Met, Tspan8, alpha6beta4, CXCR4, CD133, EpCAM and claudin7. The functional relevance of CSC markers is still disputed. We hypothesize that Pa-CSC markers play a decisive role in tumor progression. This is fostered by the location in glycolipid-enriched membrane domains, which function as signaling platform and support connectivity of the individual Pa-CSC markers. Outside-in signaling supports apoptosis resistance, stem cell gene expression and tumor suppressor gene repression as well as miRNA transcription and silencing. Pa-CSC markers also contribute to motility and invasiveness. By ligand binding host cells are triggered towards creating a milieu supporting Pa-CSC maintenance. Furthermore, CSC markers contribute to the generation, loading and delivery of exosomes, whereby CSC gain the capacity for a cell-cell contact independent crosstalk with the host and neighboring non-CSC. This allows Pa-CSC exosomes (TEX) to reprogram neighboring non-CSC towards epithelial mesenchymal transition and to stimulate host cells towards preparing a niche for metastasizing tumor cells. Finally, TEX communicate with the matrix to support tumor cell motility, invasion and homing. We will discuss the possibility that CSC markers are the initial trigger for these processes and what is the special contribution of CSC-TEX. PMID:27468191

Resource Utilization for Patients with Intracerebral Hemorrhage Transferred to a Comprehensive Stroke Center.

PubMed

Nguyen, Claude; Mir, Osman; Vahidy, Farhaan; Wu, Tzu-Ching; Albright, Karen; Boehme, Amelia; Delgado, Rigoberto; Savitz, Sean

2015-12-01

As a comprehensive stroke center (CSC), we accept transfer patients with intracerebral hemorrhage (ICH) in our region. CSC guidelines mandate receipt of patients with ICH for higher level of care. We determined resource utilization of patients accepted from outside hospitals compared with patients directly arriving to our center. From our stroke registry, we compared patients with primary ICH transferred to those directly arriving to our CSC from March 2011-March 2012. We compared the proportion of patients who utilized at least one of these resources: neurointensive care unit (NICU), neurosurgical intervention, or clinical trial enrollment. Among the 362 patients, 210 (58%) were transfers. Transferred patients were older, had higher median Glasgow Coma Scale scores, and lower National Institutes of Health Stroke Scale scores than directly admitted patients. Transfers had smaller median ICH volumes (20.5 cc versus 15.2 cc; P = .04) and lower ICH scores (2.1 ± 1.4 versus 1.6 ± 1.3; P < .01). A smaller proportion of transfers utilized CSC-specific resources compared with direct admits (P = .02). Fewer transferred patients required neurosurgical intervention or were enrolled in trials. No significant difference was found in the proportion of patients who used NICU resources, although transferred patients had a significantly lower length of stay in the NICU. Average hospital stay costs were less for transferred patients than for direct admits. Patients with ICH transferred to our CSC underwent fewer neurosurgical procedures and had a shorter stay in the NICU. These results were reflected in the lower per-patient costs in the transferred group. Our results raise the need to analyze cost-benefits and resource utilization of transferring patients with milder ICH. Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Cushing's Syndrome and Hypothalamic-Pituitary-Adrenal Axis Hyperactivity in Chronic Central Serous Chorioretinopathy.

PubMed

van Haalen, Femke M; van Dijk, Elon H C; Dekkers, Olaf M; Bizino, Maurice B; Dijkman, Greet; Biermasz, Nienke R; Boon, Camiel J F; Pereira, Alberto M

2018-01-01

Central serous chorioretinopathy (CSC), a specific form of macular degeneration, has been reported as presenting manifestation of Cushing's syndrome. Furthermore, CSC has been associated with both exogenous hypercortisolism and endogenous Cushing's syndrome. It is important to know whether CSC patients should be screened for Cushing's syndrome. Although hypothalamic-pituitary-adrenal (HPA) axis hyperactivity in CSC has been suggested, no detailed evaluation of the HPA axis has been performed in a large cohort of CSC patients. This study aimed to investigate whether Cushing's syndrome prevalence is increased among chronic CSC (cCSC) patients and whether detailed endocrinological phenotyping indicates hyperactivity of the HPA axis. Cross-sectional study. 86 cCSC patients and 24 controls. Prevalence of Cushing's syndrome, HPA axis activity. None of the cCSC patients met the clinical or biochemical criteria of Cushing's syndrome. However, compared to controls, HPA axis activity was increased in cCSC patients, reflected by higher 24 h urinary free cortisol, and accompanying higher waist circumference and diastolic blood pressure, whereas circadian cortisol rhythm and feedback were not different. Chronic CSC patients did not report more stress or stress-related problems on questionnaires. No case of Cushing's syndrome was revealed in a large cohort of cCSC patients. Therefore, we advise against screening for Cushing's syndrome in CSC patients, unless additional clinical features are present. However, our results indicate that cCSC is associated with hyperactivity of the HPA axis, albeit not accompanied with perception of more psychosocial stress.

Long Non-Coding RNA HOTAIR Regulates the Proliferation, Self-Renewal Capacity, Tumor Formation and Migration of the Cancer Stem-Like Cell (CSC) Subpopulation Enriched from Breast Cancer Cells.

PubMed

Deng, Jia; Yang, Mengchang; Jiang, Rong; An, Ning; Wang, Xiaoshan; Liu, Bin

2017-01-01

Long non-coding RNAs (lncRNAs) play important roles in the malignant behavior of cancer. HOTAIR, a well-studied lncRNA, contributes to breast cancer development, and overexpression of HOTAIR predicts a poor prognosis. However, the regulatory role of HOTAIR in the cancer stem-like cell (CSC) subpopulation remains largely unknown. Our goal was to determine the regulatory functions of HOTAIR in the processes of self-renewal capacity, tumor formation and proliferation of CSCs derived from breast cancer. We first enriched and incubated the CSC population derived from breast cancer cell line MCF7 (CSC-MCF7) or MDA-MB-231 (MB231, CSC-MB231). Self-renewal capacity and tumor formation were assessed in vitro and in vivo to determine the stemness of CSCs. We assessed the impact on ectopically upregulated or downregulated expression of HOTAIR in CSCs by soft agar, self-renewal capacity and CCK-8 assays. The functional domain of HOTAIR was determined by truncation. RT-qPCR and semiquantitative Western blotting were performed to detect the expression levels of genes of interest. Chromatin IP (ChIP) was employed to detect the transcriptional regulatory activity of p53 on its target gene. After the identification of CSC properties, RT-qPCR analysis revealed that HOTAIR, but not other cancer-associated lncRNAs, is highly upregulated in both CSC-MCF7 and CSC-MB231 populations compared with MCF7 and MB231 populations. By modulating the level of HOTAIR expression, we showed that HOTAIR tightly regulates the proliferation, colony formation, migration and self-renewal capacity of CSCs. Moreover, full-length HOTAIR transcriptionally inhibits miR-34a specifically, leading to upregulation of Sox2, which is targeted by miR-34a. Ectopic introduction of miR-34a mimics reverses the effects of HOTAIR on the physiological processes of CSCs, indicating that HOTAIR affects these processes, including self-renewal capacity; these effects are dependent on the regulation of Sox2 via miR-34a. Interestingly, tight transcriptional regulation of p53 by HOTAIR was found; accordingly, p21 is indirectly regulated by HOTAIR, resulting in cell cycle entry. These results suggest that HOTAIR is a key regulator of proliferation, colony formation, invasion and self-renewal capacity in breast CSCs, which occurs in part through regulation of Sox2 and p53.

Anti-Tumor Activity of a Novel Compound-CDF Is Mediated by Regulating miR-21, miR-200, and PTEN in Pancreatic Cancer

PubMed Central

Kong, Dejuan; Sarkar, Sanila H.; Wang, Zhiwei; Banerjee, Sanjeev; Aboukameel, Amro; Padhye, Subhash; Philip, Philip A.; Sarkar, Fazlul H.

2011-01-01

Background The existence of cancer stem cells (CSCs) or cancer stem-like cells in a tumor mass is believed to be responsible for tumor recurrence because of their intrinsic and extrinsic drug-resistance characteristics. Therefore, targeted killing of CSCs would be a newer strategy for the prevention of tumor recurrence and/or treatment by overcoming drug-resistance. We have developed a novel synthetic compound-CDF, which showed greater bioavailability in animal tissues such as pancreas, and also induced cell growth inhibition and apoptosis, which was mediated by inactivation of NF-κB, COX-2, and VEGF in pancreatic cancer (PC) cells. Methodology/Principal Findings In the current study we showed, for the first time, that CDF could significantly inhibit the sphere-forming ability (pancreatospheres) of PC cells consistent with increased disintegration of pancreatospheres, which was associated with attenuation of CSC markers (CD44 and EpCAM), especially in gemcitabine-resistant (MIAPaCa-2) PC cells containing high proportion of CSCs consistent with increased miR-21 and decreased miR-200. In a xenograft mouse model of human PC, CDF treatment significantly inhibited tumor growth, which was associated with decreased NF-κB DNA binding activity, COX-2, and miR-21 expression, and increased PTEN and miR-200 expression in tumor remnants. Conclusions/Significance These results strongly suggest that the anti-tumor activity of CDF is associated with inhibition of CSC function via down-regulation of CSC-associated signaling pathways. Therefore, CDF could be useful for the prevention of tumor recurrence and/or treatment of PC with better treatment outcome in the future. PMID:21408027

76 FR 37822 - General Meeting Registration and Evaluation

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-28

...), National Protection and Programs Directorate (NPPD, Office of Cybersecurity and Communications (CS&C... Cybersecurity and Communications, Office of Emergency Communications. Title: General Meeting Registration and...

Radiopacifier Particle Size Impacts the Physical Properties of Tricalcium Silicate–based Cements

PubMed Central

Saghiri, Mohammad Ali; Gutmann, James L.; Orangi, Jafar; Asatourian, Armen; Sheibani, Nader

2016-01-01

Introduction The aim of this study was to evaluate the impact of radiopaque additive, bismuth oxide, particle size on the physical properties, and radiopacity of tricalcium silicate–based cements. Methods Six types of tricalcium silicate cement (CSC) including CSC without bismuth oxide, CSC + 10% (wt%) regular bismuth oxide (particle size 10 μm), CSC + 20% regular bismuth oxide (simulating white mineral trioxide aggregate [WMTA]) as a control, CSC + 10% nano bismuth oxide (particle size 50–80 nm), CSC + 20% nano-size bismuth oxide, and nano WMTA (a nano modification of WMTA comprising nanoparticles in the range of 40–100 nm) were prepared. Twenty-four samples from each group were divided into 4 groups and subjected to push-out, surface microhardness, radiopacity, and compressive strength tests. Data were analyzed by 1-way analysis of variance with the post hoc Tukey test. Results The push-out and compressive strength of CSC without bismuth oxide and CSC with 10% and 20% nano bismuth oxide were significantly higher than CSC with 10% or 20% regular bismuth oxide (P < .05). The surface micro-hardness of CSC without bismuth oxide and CSC with 10% regular bismuth oxide had the lowest values (P < .05). The lowest radiopacity values were seen in CSC without bismuth oxide and CSC with 10% nano bismuth oxide (P < .05). Nano WMTA samples showed the highest values for all tested properties (P < .05) except for radiopacity. Conclusions The addition of 20% nano bismuth oxide enhanced the physical properties of CSC without any significant changes in radiopacity. Regular particle-size bismuth oxide reduced the physical properties of CSC material for tested parameters. PMID:25492489

76 FR 43696 - Nationwide Cyber Security Review (NCSR) Assessment

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-21

... DEPARTMENT OF HOMELAND SECURITY [Docket No. DHS-2011-0012] Nationwide Cyber Security Review (NCSR... Protection and Programs Directorate (NPPD), Office of Cybersecurity and Communications (CS&C), National Cyber Security Division (NCSD), Cyber Security Evaluation Program (CSEP), will submit the following Information...

Design Document for the Moods Data Management System (MDMS) Version 1.0

DTIC Science & Technology

1994-08-01

1 1.3 Document Overview ... . . . . . . . . . . . . . . . . . . . . 1 2 RERENCED DOCUMENTS .................... 2 3 PRELIM[INARY DESIGN... 3 3.1.1.1 CSC-: Grpical User Interfce(GUI).......... 3 3.1.112 CSC-2: Data Management Module (DMM) .................. 4 3.1.1.3 CSC- 3 : Data...5 3.1.1.6 GUI-DMM (CSC-1ICSC-2) internal interface................5 3.1.1.7 GUI-DAM (CSC-1/CSC- 3 ) Internal Interface................5

The hitchhikers guide to cancer stem cell theory: markers, pathways and therapy.

PubMed

Fábián, Ákos; Vereb, György; Szöllősi, János

2013-01-01

Cancer stem cell (CSC) biology is a rapidly developing field within cancer research. CSCs are postulated to be a unique cell population exclusively capable of infinite self renewal, multilineage differentiation and with ability to evade conventional cytotoxic cancer therapy. These traits distinguish CSCs from their more differentiated counterparts, which possess only limited or no potential for self renewal and tumor initiation. Therefore, CSCs would be the driving motor of malignant growth and therapy resistance. Accordingly, successful cancer treatment would need to eliminate this highly potent group of cells, since even small residual numbers would suffice to recapitulate the disease after therapy. Putative CSCs has been identified in a broad range of human malignancies and several cell surface markers have been associated with their stem cell phenotype. Despite all efforts, a pure CSC population has not been isolated and often in vitro clonogenic and in vivo tumorigenic potential is found in several cell populations with occasionally contradictory surface marker signatures. Here, we give a brief overview of recent advances in CSC theory, including the signaling pathways in CSCs that also appear crucial for stem cells homeostasis in normal tissues. We discuss evidence for the interaction of CSCs with the stromal tumor environment. Finally, we review the emerging potentially effective CSC-targeted treatment strategies and their future role in therapy. Copyright © 2012 International Society for Advancement of Cytometry.

Silibinin strongly inhibits the growth kinetics of colon cancer stem cell-enriched spheroids by modulating interleukin 4/6-mediated survival signals

PubMed Central

Agarwal, Chapla; Agarwal, Rajesh

2014-01-01

Involvement of cancer stem cells (CSC) in initiation, progression, relapse, and therapy-resistance of colorectal cancer (CRC) warrants search for small molecules as ‘adjunct-therapy’ to target both colon CSC and bulk tumor population. Herein, we assessed the potential of silibinin to eradicate colon CSC together with associated molecular mechanisms. In studies examining how silibinin modulates dynamics of CSC spheroids in terms of its effect on kinetics of CSC spheroids generated in presence of mitogenic and interleukin (IL)-mediated signaling which provides an autocrine/paracrine amplification loop in CRC, silibinin strongly decreased colon CSC pool together with cell survival of bulk tumor cells. Silibinin effect on colon CSC was mediated via blocking of pro-tumorigenic signaling, notably IL-4/-6 signaling that affects CSC population. These silibinin effects were associated with decreased mRNA and protein levels of various CSC-associated transcription factors, signaling molecules and markers. Furthermore, 2D and 3D differentiation assays indicated formation of more differentiated clones by silibinin. These results highlight silibinin potential to interfere with kinetics of CSC pool by shifting CSC cell division to asymmetric type via targeting various signals associated with the survival and multiplication of colon CSC pool. Together, our findings further support clinical usefulness of silibinin in CRC intervention and therapy. PMID:24970802

Caring School Community[TM] (Formerly, the Child Development Project). What Works Clearinghouse Intervention Report

ERIC Educational Resources Information Center

What Works Clearinghouse, 2006

2006-01-01

"Caring School Community[TM]" ("CSC") is a modified version of a program formerly known as the "Child Development Project." The program aims to promote core values, prosocial behavior, and a schoolwide feeling of community. The program consists of four elements originally developed for the "Child Development…

Ada Compiler Validation Summary Report: Certificate Number: 900121S1. 10251 Computer Sciences Corporation MC Ada V1.2.Beta/Concurrent Computer Corporation Concurrent/Masscomp 5600 Host To Concurrent/Masscomp 5600 (Dual 68020 Processor Configuration) Target

DTIC Science & Technology

1990-04-23

developed Ada Real - Time Operating System (ARTOS) for bare machine environments(Target), ACW 1.1I0. " ; - -M.UIECTTERMS Ada programming language, Ada...configuration) Operating System: CSC developed Ada Real - Time Operating System (ARTOS) for bare machine environments Memory Size: 4MB 2.2...Test Method Testing of the MC Ado V1.2.beta/ Concurrent Computer Corporation compiler and the CSC developed Ada Real - Time Operating System (ARTOS) for

78 FR 71630 - New Information Collection Request; General Meeting Registration and Evaluation

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-29

... of Cybersecurity and Communications (CS&C), Office of Emergency Communications (OEC) will submit the... and Programs Directorate, Office of Cybersecurity and Communications, Office of Emergency...

Physicochemical properties of calcium silicate cements associated with microparticulate and nanoparticulate radiopacifiers.

PubMed

Bosso-Martelo, Roberta; Guerreiro-Tanomaru, Juliane M; Viapiana, Raqueli; Berbert, Fabio Luiz C; Duarte, Marco Antonio Hungaro; Tanomaru-Filho, Mário

2016-01-01

The objective of this paper was to evaluate the physicochemical properties of calcium silicate cements with different chemical compositions, associated with radiopacifying agents. Mineral trioxide aggregate (MTA) Angelus, calcium silicate cement with additives (CSC), and resinous calcium silicate cement (CSCR) were evaluated, with the addition of the following radiopacifiers: microparticles (micro) or nanoparticles (nano) of zirconium oxide (ZrO(2)), niobium oxide (Nb(2)O(5)), bismuth oxide (Bi(2)O(3)), or calcium tungstate (CaWO(4)). Setting time was evaluated using Gilmore needles. Solubility was determined after immersion in water. The pH and calcium ion release were analyzed after 3, 12, and 24 h and 7, 14, and 21 days. The data obtained were submitted to analysis of variance and Tukey's test, at a level of significance of 5 %. CSC + CaWO(4) and CSCR + ZrO(2) micro, Nb(2)O(5) and CaWO(4) presented results similar to MTA, with a shorter final setting time than the other associations. CSC and CSCR+ ZrO(2) micro presented a higher degree of flow. All the cements evaluated presented low solubility. The materials presented alkaline pH and released calcium ions. ZrO(2) micro radiopacifier may be considered a potential substitute for Bi(2)O(3) when associated with CSC or CSCR. The proposed materials, especially when associated with ZrO(2), are potential materials for use as alternatives to MTA.

Selective Retina Therapy in Acute and Chronic-Recurrent Central Serous Chorioretinopathy.

PubMed

Framme, Carsten; Walter, Andreas; Berger, Lieselotte; Prahs, Philipp; Alt, Clemens; Theisen-Kunde, Dirk; Kowal, Jens; Brinkmann, Ralf

2015-01-01

Selective retina therapy (SRT), the confined laser heating and destruction of retinal pigment epithelial cells, has been shown to treat acute types of central serous chorioretinopathy (CSC) successfully without damaging the photoreceptors and thus avoiding laser-induced scotoma. However, a benefit of laser treatment for chronic forms of CSC is questionable. In this study, the efficacy of SRT by means of the previously used 1.7-µs and shorter 300-ns pulse duration was evaluated for both types of CSC, also considering re-treatment for nonresponders. In a two-center trial, 26 patients were treated with SRT for acute (n = 10) and chronic-recurrent CSC (n = 16). All patients presented with subretinal fluid (SRF) in OCT and leakage in fluorescein angiography (FA). SRT was performed using a prototype SRT laser system (frequency-doubled Q-switched Nd:YLF-laser, wavelength 527 nm) with adjustable pulse duration. The following irradiation settings were used: a train of 30 laser pulses with a repetition rate of 100 Hz and pulse durations of 300 ns and 1.7 µs, pulse energy 120-200 µJ, retinal spot size 200 µm. Because SRT lesions are invisible, FA was always performed 1 h after treatment to demonstrate laser outcome (5-8 single spots in the area of leakage). In cases where energy was too low, as indicated by missing FA leakage, energy was adjusted and the patient re-treated immediately. Observation intervals were after 4 weeks and 3 months. In case of nonimprovement of the disease after 3 months, re-treatment was considered. Of 10 patients with active CSC that presents focal leakage in FA, 5 had completely resolved fluid after 4 weeks and all 10 after 3 months. Mean visual acuity increased from 76.6 ETDRS letters to 85.0 ETDRS letters 3 months after SRT. Chronic-recurrent CSC was characterized by less severe SRF at baseline in OCT and weaker leakage in FA than in acute types. Visual acuity changed from baseline 71.6 to 72.8 ETDRS letters after 3 months. At this time, SRF was absent in 3 out of 16 patients (19%), FA leakage had come to a complete stop in 6 out of 16 patients (38%). In 6 of the remaining chronic CSC patients, repeated SRT with higher pulse energy was considered because of persistent leakage activity. After the re-treatment, SRF resolved completely in 5 patients (83.3%) after only 25 days. SRT showed promising results in treating acute CSC, but was less effective in chronic cases. Interestingly, re-treatment resulted in enhanced fluid resolution and dry conditions after a considerably shorter time in most patients. Therefore, SRT including re-treatment if necessary might be a valuable CSC treatment alternative even in chronic-recurrent cases. © 2015 S. Karger AG, Basel.

Effects of different types of moderate severity disturbance on forest structural complexity and ecosystem functioning: A story of ice and fire

NASA Astrophysics Data System (ADS)

Fahey, R. T.; Atkins, J.; Gough, C. M.; Hardiman, B. S.; Haber, L.; Stuart-Haentjens, E.; David, O.; Campbell, J. L.; Rustad, L.; Duffy, M.

2017-12-01

Disturbances that alter the structure and function of forest ecosystems occur along a continuum of severity. In contrast to the extremes of the disturbance gradient (i.e., stand-replacing disturbance and small gap formation), moderate severity disturbances are poorly understood, even though they make up the majority of the gradient and their spatial extent (and likely overall importance to regional disturbance regimes) often exceeds that of more severe disturbances. Moderate severity disturbances originate from a variety of causes, such as fires, ice storms, or pest and pathogen outbreaks, and each of these could reshape structure and function in different ways. Observational data from a limited number of sites shows that moderate disturbance can increase ecosystem complexity, but the generality of this effect has not been tested across a broad range of disturbance types and severities. Here, we utilize data from a set of five case studies of experimental or natural moderate disturbance to assess the effects of different types and severities of disturbance on forest canopy structural complexity (CSC) and the relationship of canopy structure with ecosystem functioning. Using pre- and post-disturbance measures of CSC derived from aerial and terrestrial LiDAR, UAV imagery, and Landsat data we quantified changes in CSC following an experimental ice storm, a low-severity surface fire, Beech Bark Disease and Hemlock Wooly Adelgid outbreaks, and experimental accelerated succession. Our initial findings indicate that different disturbance types have highly variable effects on CSC, and also that progressive increases in disturbance severity alter CSC differently among disturbance types. Differential effects of variable disturbance types on CSC has implications for the carbon cycle, as forest structure is strongly linked with both growth-limiting resource (e.g., nutrients and light) acquisition and net primary productivity. Understanding how different types and severities of moderate disturbance affect canopy structural complexity is thus crucial to informing and improving modeling the earth system and predicting how global shifts in moderate disturbance type, frequency, and severity will alter the land carbon sink.

Regulation of Ovarian Cancer Stem Cells or Tumor-Initiating Cells

PubMed Central

Kwon, Mi Jeong; Shin, Young Kee

2013-01-01

Cancer stem cells or tumor-initiating cells (CSC/TICs), which can undergo self-renewal and differentiation, are thought to play critical roles in tumorigenesis, therapy resistance, tumor recurrence and metastasis. Tumor recurrence and chemoresistance are major causes of poor survival rates of ovarian cancer patients, which may be due in part to the existence of CSC/TICs. Therefore, elucidating the molecular mechanisms responsible for the ovarian CSC/TICs is required to develop a cure for this malignancy. Recent studies have indicated that the properties of CSC/TICs can be regulated by microRNAs, genes and signaling pathways which also function in normal stem cells. Moreover, emerging evidence suggests that the tumor microenvironments surrounding CSC/TICs are crucial for the maintenance of these cells. Similarly, efforts are now being made to unravel the mechanism involved in the regulation of ovarian CSC/TICs, although much work is still needed. This review considers recent advances in identifying the genes and pathways involved in the regulation of ovarian CSC/TICs. Furthermore, current approaches targeting ovarian CSC/TICs are described. Targeting both CSC/TICs and bulk tumor cells is suggested as a more effective approach to eliminating ovarian tumors. Better understanding of the regulation of ovarian CSC/TICs might facilitate the development of improved therapeutic strategies for recurrent ovarian cancer. PMID:23528891

Selective Targeting of Cancer Stem Cells by 2-Aminodihydroquinoline Analogs.

PubMed

Park, Heejoo; Yu, Yeongji; Kim, Hyejin; Lee, Eun; Lee, Hani; Jeon, Raok; Kim, Woo-Young

2017-04-01

Many aminodihydroquinoline compounds have been studied to determine their cytotoxicity to cancer cells. However, anti-cancer stem cells (CSCs) activity of aminodihydroquinoline has not been tested in spite that CSC is believed to do an important roles in chemotherapy resistance and recurrence. The CSC selective targeting activities of 10 recently synthesized 2-aminodihydroquinoline analogs were examined on CSCs and bulk culture of a glioblastoma cell line. A diethylaminopropyl substituted aminodihydroquinoline, 5h, showed a strong anti-CSC effect and general cytotoxicity. However, a benzyl substituted aminodihydroquinoline, 5i, displayed the most effective anti-CSC effect, with no or small significant cytotoxic effect in bulk culture conditions. While 5h temporarily enhanced CSC marker-positive cells and eventually suppressed the CSC population, which is similar to other cytotoxic anticancer reagents reported, 5i selectively eliminated CSC marker-positive cells based on fluorescence activated cell sorter (FACS) analysis. 5h also temporarily activated some genes associated with signaling required for CSC, while 5i selectively suppressed these genes supporting that the differential effects are resulted from different molecular responses. In addition, the selective CSC effect is also found against a colon cancer cell line. Collectively, we suggest that these two novel aminodihydroquinoline compounds possess novel anti-CSC effects in colon and brain tumor derived cell lines probably through independent pathways.

Targeting Glioblastoma with the Use of Phytocompounds and Nanoparticles.

PubMed

Pistollato, Francesca; Bremer-Hoffmann, Susanne; Basso, Giuseppe; Cano, Sandra Sumalla; Elio, Iñaki; Vergara, Manuel Masias; Giampieri, Francesca; Battino, Maurizio

2016-02-01

Glioblastoma multiforme (GBM) are extremely lethal and still poorly treated primary brain tumors, characterized by the presence of highly tumorigenic cancer stem cell (CSC) subpopulations, considered responsible for tumor relapse. In order to successfully eradicate GBM growth and recurrence, new anti-cancer strategies selectively targeting CSCs should be designed. CSCs might be eradicated by targeting some of their cell surface markers and transporters, inducing their differentiation, impacting their hyper-glycolytic metabolism, inhibiting CSC-related signaling pathways and/or by targeting their microenvironmental niche. In this regard, phytocompounds such as curcumin, isothiocyanates, resveratrol and epigallocatechin-3-gallate have been shown to prevent or reverse cancer-related epigenetic dysfunctions, reducing tumorigenesis, preventing metastasis and/or increasing chemotherapy and radiotherapy efficacy. However, the actual bioavailability and metabolic processing of phytocompounds is generally unknown, and the presence of the blood brain barrier often represents a limitation to glioma treatments. Nowadays, nanoparticles (NPs) can be loaded with therapeutic compounds such as phytochemicals, improving their bioavailability and their targeted delivery within the GBM tumor bulk. Moreover, NPs can be designed to increase their tropism and specificity toward CSCs by conjugating their surface with antibodies specific for CSC antigens, with ligands or with glucose analogues. Here we discuss the use of phytochemicals as anti-glioma agents and the applicability of phytochemical-loaded NPs as drug delivery systems to target GBM. Additionally, we provide some examples on how NPs can be specifically formulated to improve CSC targeting.

Identification, expansion and characterization of cancer cells with stem cell properties from head and neck squamous cell carcinomas

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

Kaseb, Hatem O.; Department of Clinical Pathology, National Cancer Institute; Fohrer-Ting, Helene

Head and neck squamous cell carcinoma (HNSCC) is a major public health concern. Recent data indicate the presence of cancer stem cells (CSC) in many solid tumors, including HNSCC. Here, we assessed the stem cell (SC) characteristics, including cell surface markers, radioresistance, chromosomal instability, and in vivo tumorigenic capacity of CSC isolated from HNSCC patient specimens. We show that spheroid enrichment of CSC from early and short-term HNSCC cell cultures was associated with increased expression of CD44, CD133, SOX2 and BMI1 compared with normal oral epithelial cells. On immunophenotyping, five of 12 SC/CSC markers were homogenously expressed in all tumormore » cultures, while one of 12 was negative, four of 12 showed variable expression, and two of the 12 were expressed heterogeneously. We showed that irradiated CSCs survived and retained their self-renewal capacity across different ionizing radiation (IR) regimens. Fluorescence in situ hybridization (FISH) analyses of parental and clonally-derived tumor cells revealed different chromosome copy numbers from cell to cell, suggesting the presence of chromosomal instability in HNSCC CSC. Further, our in vitro and in vivo mouse engraftment studies suggest that CD44+/CD66− is a promising, consistent biomarker combination for HNSCC CSC. Overall, our findings add further evidence to the proposed role of HNSCC CSCs in therapeutic resistance. - Highlights: • Spheroid enrichment selects cancer stem cells (CSC) from head & neck tumors (HNSCC). • Compared to normal epithelial cells, isolated CSC express increased SC/CSC markers. • Isolated CSC display enhanced radioresistance, clonogenicity and tumorigenicity. • HNSCC CSC express chromosomal instability. • CD44+/CD66− is a promising, consistent biomarker for HNSCC CSC.« less

Targeting proapoptotic protein BAD inhibits survival and self-renewal of cancer stem cells.

PubMed

Sastry, K S R; Al-Muftah, M A; Li, Pu; Al-Kowari, M K; Wang, E; Ismail Chouchane, A; Kizhakayil, D; Kulik, G; Marincola, F M; Haoudi, A; Chouchane, L

2014-12-01

Emerging evidence suggests that the resistance of cancer stem cells (CSC) to many conventional therapies is one of the major limiting factors of cancer therapy efficacy. Identification of mechanisms responsible for survival and self-renewal of CSC will help design new therapeutic strategies that target and eliminate both differentiated cancer cells and CSC. Here we demonstrated the potential role of proapoptotic protein BAD in the biology of CSC in melanoma, prostate and breast cancers. We enriched CD44(+)/CD24(-) cells (CSC) by tumorosphere formation and purified this population by FACS. Both spheres and CSC exhibited increased potential for proliferation, migration, invasion, sphere formation, anchorage-independent growth, as well as upregulation of several stem cell-associated markers. We showed that the phosphorylation of BAD is essential for the survival of CSC. Conversely, ectopic expression of a phosphorylation-deficient mutant BAD induced apoptosis in CSC. This effect was enhanced by treatment with a BH3-mimetic, ABT-737. Both pharmacological agents that inhibit survival kinases and growth factors that are involved in drug resistance delivered their respective cytotoxic and protective effects by modulating the BAD phosphorylation in CSC. Furthermore, the frequency and self-renewal capacity of CSC was significantly reduced by knocking down the BAD expression. Consistent with our in vitro results, significant phosphorylation of BAD was found in CD44(+) CSC of 83% breast tumor specimens. In addition, we also identified a positive correlation between BAD expression and disease stage in prostate cancer, suggesting a role of BAD in tumor advancement. Our studies unveil the role of BAD in the survival and self-renewal of CSC and propose BAD not only as an attractive target for cancer therapy but also as a marker of tumor progression.

Canopy structural complexity as a continental predictor of primary production: Using NEON to transform understanding of forest structure-function

NASA Astrophysics Data System (ADS)

Atkins, J. W.; Fahey, R. T.; Gough, C. M.; Hardiman, B. S.

2016-12-01

Ecosystem structure-function relationships represent a long-standing research area for ecosystem science. Relationships between canopy structural complexity (CSC) and net primary productivity (NPP), have been characterized for a limited number of sites, yet whether these relationships are conserved across eco-climatic boundaries remains unknown. We hypothesize an underlying mechanistic basis for global NPP-CSC linkages to include improved resource-use efficiency as CSC increases, examined here by correlating CSC with measures of light-use efficiency and nitrogen-use efficiency. Here we present a broad, continental scale analysis of CSC-NPP linkages. We are using multiple NEON sites coupled with other sites across a diverse array of temperate forest types spanning six eco-climatic domains of the continental United States to examine CSC-NPP relationships. Portable canopy LiDAR (PCL) data were used to calculate a suite of CSC metrics at the plot-level within each site. Ongoing work compares CSC to co-located measurements of wood net primary production estimated from the incremental change in woody biomass calculated using tree allometries. Results to date show CSC is highly variable across forest sites and may provide additional explanatory power for predicting NPP that is independent of other commonly used forest structural attributes such as leaf area index. CSC metrics such as rugosity vary widely across sites—ranging from high values (30 - 35) in complex canopies such as the Great Smoky Mountains to low values in open, savanna systems like North-Central Florida (< 0.5 - 2). NPP, and light- and nitrogen-use calculations are underway and will be paired with site-level CSC, with the expectation that CSC, resource-use efficiency, and NPP are positively correlated. Advancing understanding of how and why CSC affects forest NPP across a broad spatial dimension could transform mechanistic understanding of ecosystem structure-carbon cycling relationships, and greatly improve carbon cycling models and remote sensing applications, while providing a crucial linkage between the two.

Identification of a selective small molecule inhibitor of breast cancer stem cells.

PubMed

Germain, Andrew R; Carmody, Leigh C; Morgan, Barbara; Fernandez, Cristina; Forbeck, Erin; Lewis, Timothy A; Nag, Partha P; Ting, Amal; VerPlank, Lynn; Feng, Yuxiong; Perez, Jose R; Dandapani, Sivaraman; Palmer, Michelle; Lander, Eric S; Gupta, Piyush B; Schreiber, Stuart L; Munoz, Benito

2012-05-15

A high-throughput screen (HTS) with the National Institute of Health-Molecular Libraries Small Molecule Repository (NIH-MLSMR) compound collection identified a class of acyl hydrazones to be selectively lethal to breast cancer stem cell (CSC) enriched populations. Medicinal chemistry efforts were undertaken to optimize potency and selectivity of this class of compounds. The optimized compound was declared as a probe (ML239) with the NIH Molecular Libraries Program and displayed greater than 20-fold selective inhibition of the breast CSC-like cell line (HMLE_sh_Ecad) over the isogenic control line (HMLE_sh_GFP). Copyright © 2012 Elsevier Ltd. All rights reserved.

Stem cells in gastrointestinal cancers: The road less travelled

PubMed Central

Mikhail, Sameh; Zeidan, Amer

2014-01-01

Cancer stem cells (CSC) are thought to be malignant cells that have the capacity to initiate and maintain tumor growth and survival. Studies have described CSC in various gastrointestinal neoplasms such as colon, pancreas and liver and gastroesophageal tumors. The mechanism by which CSC develop remains unclear. Several studies have explored the role of dysregulation of the Wnt/β-catenin, transformation growth factor-beta and hedhog pathways in generation of CSC. In this review, we discuss the various molecular abnormalities that may be related to formation of CSC in gastrointestinal malignancies, strategies to identify CSC and therapeutic strategies that are based on these concepts. Identification and targeting CSC is an intriguing area and may provide a new therapeutic option for patients with cancer including gastrointestinal malignancies. Although great progress has been made, many issues need to be addressed. Precise targeting of CSC will require precise isolation and characterization of those cells. This field is also evolving but further research is needed to identify markers that are specific for CSC. Although the application of this field has not entered the clinic yet, there continues to be significant optimism about its potential utility in overcoming cancer resistance and curing patients with cancer. PMID:25426257

CSC-3436 switched tamoxifen-induced autophagy to apoptosis through the inhibition of AMPK/mTOR pathway.

PubMed

Wu, Sheng-Tang; Sun, Guang-Huan; Cha, Tai-Lung; Kao, Chien-Chang; Chang, Sun-Yran; Kuo, Sheng-Chu; Way, Tzong-Der

2016-08-15

Triple-negative breast cancer (TNBC) lacks specific therapeutic target and limits to chemotherapy and is essential to develop novel therapeutic regimens. Increasing studies indicated that tamoxifen, a selective estrogen receptor modulators (SERMs), has anti-tumor therapeutic effect in estrogen receptor α (ERα)-negative tumor. Here, we determined whether autophagy was activated by tamoxifen in TNBC cells. Moreover, CSC-3436 displayed strong and selective growth inhibition on cancer cells. Next, we investigated the anti-proliferation effect of combination of CSC-3436 plus tamoxifen on cell death in TNBC cells. Our study found that tamoxifen induces autophagy in TNBC cells. Endoplasmic reticulum stress and AMPK/mTOR contributed tamoxifen-induced autophagy. Interestingly, in combination treatment with CSC-3436 enhanced the anti-proliferative effect of tamoxifen. We found that CSC-3436 switched tamoxifen-induced autophagy to apoptosis via cleavage of ATG-5. Moreover, AMPK/mTOR pathway may involve in CSC-3436 switched tamoxifen-induced autophagy to apoptosis. The combination of tamoxifen and CSC-3436 produced stronger tumor growth inhibition compared with CSC-3436 or tamoxifen alone treatments in vivo. These data indicated that CSC-3436 combined with tamoxifen may be a potential approach for treatment TNBC.

Activities of the Center for Space Construction

NASA Technical Reports Server (NTRS)

1993-01-01

The Center for Space Construction (CSC) at the University of Colorado at Boulder is one of eight University Space Engineering Research Centers established by NASA in 1988. The mission of the center is to conduct research into space technology and to directly contribute to space engineering education. The center reports to the Department of Aerospace Engineering Sciences and resides in the College of Engineering and Applied Science. The college has a long and successful track record of cultivating multi-disciplinary research and education programs. The Center for Space Construction is prominent evidence of this record. At the inception of CSC, the center was primarily founded on the need for research on in-space construction of large space systems like space stations and interplanetary space vehicles. The scope of CSC's research has now evolved to include the design and construction of all spacecraft, large and small. Within this broadened scope, our research projects seek to impact the underlying technological basis for such spacecraft as remote sensing satellites, communication satellites, and other special purpose spacecraft, as well as the technological basis for large space platforms. The center's research focuses on three areas: spacecraft structures, spacecraft operations and control, and regolith and surface systems. In the area of spacecraft structures, our current emphasis is on concepts and modeling of deployable structures, analysis of inflatable structures, structural damage detection algorithms, and composite materials for lightweight structures. In the area of spacecraft operations and control, we are continuing our previous efforts in process control of in-orbit structural assembly. In addition, we have begun two new efforts in formal approach to spacecraft flight software systems design and adaptive attitude control systems. In the area of regolith and surface systems, we are continuing the work of characterizing the physical properties of lunar regolith, and we are at work on a project on path planning for planetary surface rovers.

An analysis of Belgian Cannabis Social Clubs' supply practices: A shapeshifting model?

PubMed

Pardal, Mafalda

2018-04-13

Cannabis Social Clubs (CSCs) are associations of cannabis users that collectively organize the cultivation and distribution of cannabis. As this middle ground supply model has been active in Belgium for over a decade, this paper aims to examine CSCs' supply practices, noting any shifts from previously reported features of the model. We draw on interviews with directors of seven currently active Belgian CSCs (n = 21) and their cannabis growers (n = 23). This data was complemented by additional fieldwork, as well as a review of CSCs' key internal documents. Most Belgian CSCs are formally registered non-profit associations. One of the Belgian CSCs has developed a structure of sub-divisions and regional chapters. The Belgian CSCs supply cannabis to members only, and in some cases only medical users are admitted. CSCs rely on in-house growers, ensuring supply in a cooperative and closed-circuit way, despite changes to the distribution methods The associations are relatively small-scale and non-commercially driven. The introduction of formal quality control practices remains challenging. As the CSC model is often included in discussions about cannabis policy, but remains in most cases driven by self-regulatory efforts, it is important to take stock of how CSCs' supply function has been implemented in practice - as doing so will improve our understanding of the model and of the wider range of cannabis 'supply architectures'. This paper highlights the continuity and changes in CSC practices, noting the emergence of several different variants of the CSC model, which are classified in a first CSC typology. Copyright © 2018 Elsevier B.V. All rights reserved.

A versatile mathematical work-flow to explore how Cancer Stem Cell fate influences tumor progression.

PubMed

Fornari, Chiara; Balbo, Gianfranco; Halawani, Sami M; Ba-Rukab, Omar; Ahmad, Ab Rahman; Calogero, Raffaele A; Cordero, Francesca; Beccuti, Marco

2015-01-01

Nowadays multidisciplinary approaches combining mathematical models with experimental assays are becoming relevant for the study of biological systems. Indeed, in cancer research multidisciplinary approaches are successfully used to understand the crucial aspects implicated in tumor growth. In particular, the Cancer Stem Cell (CSC) biology represents an area particularly suited to be studied through multidisciplinary approaches, and modeling has significantly contributed to pinpoint the crucial aspects implicated in this theory. More generally, to acquire new insights on a biological system it is necessary to have an accurate description of the phenomenon, such that making accurate predictions on its future behaviors becomes more likely. In this context, the identification of the parameters influencing model dynamics can be advantageous to increase model accuracy and to provide hints in designing wet experiments. Different techniques, ranging from statistical methods to analytical studies, have been developed. Their applications depend on case-specific aspects, such as the availability and quality of experimental data, and the dimension of the parameter space. The study of a new model on the CSC-based tumor progression has been the motivation to design a new work-flow that helps to characterize possible system dynamics and to identify those parameters influencing such behaviors. In detail, we extended our recent model on CSC-dynamics creating a new system capable of describing tumor growth during the different stages of cancer progression. Indeed, tumor cells appear to progress through lineage stages like those of normal tissues, being their division auto-regulated by internal feedback mechanisms. These new features have introduced some non-linearities in the model, making it more difficult to be studied by solely analytical techniques. Our new work-flow, based on statistical methods, was used to identify the parameters which influence the tumor growth. The effectiveness of the presented work-flow was firstly verified on two well known models and then applied to investigate our extended CSC model. We propose a new work-flow to study in a practical and informative way complex systems, allowing an easy identification, interpretation, and visualization of the key model parameters. Our methodology is useful to investigate possible model behaviors and to establish factors driving model dynamics. Analyzing our new CSC model guided by the proposed work-flow, we found that the deregulation of CSC asymmetric proliferation contributes to cancer initiation, in accordance with several experimental evidences. Specifically, model results indicated that the probability of CSC symmetric proliferation is responsible of a switching-like behavior which discriminates between tumorigenesis and unsustainable tumor growth.

Selenium suppresses leukemia through the action of endogenous eicosanoids

PubMed Central

Gandhi, Ujjawal H.; Kaushal, Naveen; Hegde, Shailaja; Finch, Emily R.; Kudva, Avinash K.; Kennett, Mary J.; Jordan, Craig T.; Paulson, Robert F.; Prabhu, K. Sandeep

2014-01-01

Eradicating cancer stem-like cells (CSC) may be essential to fully eradicate cancer. Metabolic changes in CSC could hold a key to their targeting. Here we report that the dietary micronutrient selenium can trigger apoptosis of CSC derived from chronic or acute myelogenous leukemias when administered at supraphysiological but non-toxic doses. In leukemia CSC, selenium treatment activated ATM-p53-dependent apoptosis accompanied by increased intracellular levels of reactive oxygen species. Importantly, the same treatment did not trigger apoptosis in hematopoietic stem cells. Serial transplantation studies with BCR-ABL-expressing CSC revealed that the selenium status in mice was a key determinant of CSC survival. Selenium action relied upon the endogenous production of the cyclooxygenase-derived prostaglandins Δ12-PGJ2 and 15d-PGJ2. Accordingly, non-steroidal anti-inflammatory drugs and NADPH oxidase inhibitors abrogated the ability of selenium to trigger apoptosis in leukemia CSC. Our results reveal how selenium-dependent modulation of arachidonic acid metabolism can be directed to trigger apoptosis of primary human and murine CSC in leukemia. PMID:24872387

Workforce and graduate school outcomes of NOAA's Educational Partnership Program

NASA Astrophysics Data System (ADS)

Christenson, T.; Kaplan, M.

2017-12-01

Underrepresented groups, including Black, Hispanic, Native American, Alaska Native, Native Hawaiian and Pacific Island professionals remain underrepresented in STEM fields generally, and in the ocean and atmospheric sciences specifically. NOAA has tried to address this disparity through a number of initiatives under the Educational Partnership Program with Minority Serving Institutions (EPP MSI) which currently has two components: four Cooperative Science Centers (CSCs) aligned with NOAA's mission areas; and an Undergraduate Scholarship Program (USP), both established in 2001. In order to determine the outcomes for the program participants and the impacts of these programs on degree completions and on the workforce, the EPP MSI undertook a multi-pronged effort to identify career and education achievements for 80% of the approximately 1750 EPP MSI alumni, 75% of whom are from underrepresented groups. This was accomplished through 1) searching online resources (e.g. professional web pages, LinkedIn, etc.), 2) personal communication with program-associated faculty, 3) National Student Clearinghouse, 4) a survey of former scholars conducted by Insight Policy Research, and 5) self-reporting though NOAA's Voluntary Alumni Update System. Results show that 60% of CSC alumni currently hold an advanced degree in a STEM field with another 8% currently working toward one. 66% of EPP Undergraduate Scholars go to graduate school. 72% of CSC and USP alumni are currently employed in or pursuing a graduate degree in a NOAA-related* field. More than 70 CSC graduates currently work for NOAA as contractors or federal employees while more than 240 work for other government agencies. More than 400 are employed in the private sector. Of more than 225 PhD graduates, 66 have completed or currently hold post-doctoral positions in NOAA mission fields; 71 have held faculty positions at major universities. However, one challenge is retaining diverse STEM talent within the Geosciences in light of the lure of lucrative jobs in other STEM fields and ensuring robust outcomes beyond degree completions.

HIF2α/EFEMP1 cascade mediates hypoxic effects on breast cancer stem cell hierarchy.

PubMed

Kwak, Ji-Hye; Lee, Na-Hee; Lee, Hwa-Yong; Hong, In-Sun; Nam, Jeong-Seok

2016-07-12

Breast cancer stem cells (BCSCs) have been shown to contribute to tumor growth, metastasis, and recurrence. They are also markedly resistant to conventional cancer treatments, such as chemotherapy and radiation. Recent studies have suggested that hypoxia is one of the prominent micro-environmental factors that increase the self-renewal ability of BCSCs, partially by enhancing CSC phenotypes. Thus, the identification and development of new therapeutic approaches based on targeting the hypoxia-dependent responses in BCSCs is urgent. Through various in vitro studies, we found that hypoxia specifically up-regulates BCSC sphere formation and a subset of CD44+/CD24-/low CSCs. Hypoxia inducible factors 2α (HIF2α) depletion suppressed CSC-like phenotypes and CSC-mediated drug resistance in breast cancer. Furthermore, the stimulatory effects of hypoxia-induced HIF2α on BCSC sphere formation were successfully attenuated by epidermal growth factor-containing fibulin-like extracellular matrix protein 1 (EFEMP1) knockdown. Taken together, these data suggest that HIF2α mediates hypoxia-induced cancer growth/metastasis and that EFEMP1 is a downstream effector of hypoxia-induced HIF2α during breast tumorigenesis.

Channel Storage change: a new remote sensed surface water measurement

NASA Astrophysics Data System (ADS)

Coss, S. P.; Durand, M. T.; Yi, Y.; Guo, Q.; Shum, C. K.; Allen, G. H.; Pavelsky, T.

2017-12-01

Here we present river channel storage change (CSC) measurements for 17 major world rivers from 2002-2016. We combined interpolated daily 1 km resolution Global River Radar Altimeter Time Series (GRRATS) river surface elevation data with static widths from the global river Global River Widths from Landsat (GRWL) dataset, to generate preliminary channel storage measurements. CSC is a previously unmeasured component of the terrestrial water balance It is a fundamental Earth science quantity with global bearing on floodplains, ecology, and geochemistry. CSC calculations require only remote sensed data, making them an ideal tool for studying remote regions where hydrological data is not easily accessible. CSC is uniquely suited to determine the role of hydrologic and hydraulic controls in basins with strong seasonal cycles (freeze-up and break-up). The cumulative CSC anomaly can impart spatial details that discharge measurements cannot. With this new measurement, we may be able to determine critical hydrological and hydraulic controls on rapidly changing systems like Arctic rivers. Results for Mississippi River indicate that peak CSC anomaly was the highest in 2011 (12.6 km3) and minimum CSC anomaly was in 2012 (-12.2 km3). Peak CSC has most frequently occurs in May (5 years), but has come as late in the year as July, and as early as January. Results for the Yukon River indicate that peak CSC anomaly was the highest in 2013 (13.9 km3) and minimum CSC anomaly was in 2010 (-14.2 km3). Peak CSC has most frequently come in early to mid-June (4-18), but has occurred in May (19-31) four years in the study period (three of the last 6 years) and once on April 30th.

Anti-cancer stem cell activity of a hedgehog inhibitor GANT61 in estrogen receptor-positive breast cancer cells.

PubMed

Kurebayashi, Junichi; Koike, Yoshikazu; Ohta, Yusuke; Saitoh, Wataru; Yamashita, Tetsumasa; Kanomata, Naoki; Moriya, Takuya

2017-05-01

Estradiol (E2) increases not only the cell growth but also the cancer stem cell (CSC) proportion in estrogen receptor (ER)-positive breast cancer cells. It has been suggested that the non-canonical hedgehog (Hh) pathway activated by E2 plays an important role in the regulation of CSC proportion in ER-positive breast cancer cells. We studied anti-CSC activity of a non-canonical Hh inhibitor GANT61 in ER-positive breast cancer cells. Effects of GANT61 on the cell growth, cell cycle progression, apoptosis and CSC proportion were investigated in four ER-positive breast cancer cell lines. CSC proportion was measured using either the mammosphere assay or CD44/CD24 assay. Expression levels of pivotal molecules in the Hh pathway were measured. Combined effects of GANT61 with antiestrogens on the anti-cell growth and anti-CSC activities were investigated. E2 significantly increased the cell growth and CSC proportion in all ER-positive cell lines. E2 increased the expression levels of glioma-associated oncogene (GLI) 1 and/or GLI2. GANT61 decreased the cell growth in association with a G1-S cell cycle retardation and increased apoptosis. GANT61 decreased the E2-induced CSC proportion measured by the mammosphere assay in all cell lines. Antiestrogens also decreased the E2-induced cell growth and CSC proportion. Combined treatments of GANT61 with antiestrogens additively enhanced anti-cell growth and/or anti-CSC activities in some ER-positive cell lines. In conclusion, the non-canonical Hh inhibitor GANT61 inhibited not only the cell growth but also the CSC proportion increased by E2 in ER-positive breast cancer cells. GANT61 enhanced anti-cell growth and/or anti-CSC activities of antiestrogens in ER-positive cell lines. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Inequality in cataract blindness and services: moving beyond unidimensional analyses of social position.

PubMed

Ramke, Jacqueline; Zwi, Anthony B; Lee, Arier C; Blignault, Ilse; Gilbert, Clare E

2017-04-01

Inequalities in cataract blindness are well known, but data are rarely disaggregated to explore the combined effects of a range of axes describing social disadvantage. We examined inequalities in cataract blindness and services at the intersection of three social axes. Three dichotomous social variables (sex (male/female); place of residence (urban/rural); literacy (literate/illiterate)) from cross-sectional national blindness surveys in Pakistan (2001-2004; n=16 507) and Nigeria (2005-2007; n=13 591) were used to construct eight subgroups, with disadvantaged subgroups selected a priori (ie, women, rural dwellers, illiterate). In each data set, the social distribution of cataract blindness, cataract surgical coverage (CSC) and effective cataract surgical coverage (eCSC) were examined. Inequalities were assessed comparing the best-off and worst-off subgroups using rate differences and rate ratios (RRs). Logistic regression was used to assess cumulative effects of multiple disadvantage. Disadvantaged subgroups experienced higher prevalence of cataract blindness, lower CSC and lower eCSC in both countries. A social gradient was present for CSC and eCSC, with coverage increasing as social position improved. Relative inequality in eCSC was approximately twice as high as CSC (Pakistan: eCSC RR 2.7 vs CSC RR 1.3; Nigeria: eCSC RR 8.7 vs CSC RR 4.1). Cumulative disadvantage was observed for all outcomes, deteriorating further with each additional axis along which disadvantage was experienced. Each outcome tended to be worse with the addition of each layer of social disadvantage. Illiterate, rural women fared worst in both settings. Moving beyond unidimensional analyses of social position identified subgroups in most need; this permits a more nuanced response to addressing the inequitable distribution of cataract blindness. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

The prevalence of cervical myelopathy among subjects with narrow cervical spinal canal in a population-based magnetic resonance imaging study: the Wakayama Spine Study.

PubMed

Nagata, Keiji; Yoshimura, Noriko; Hashizume, Hiroshi; Muraki, Shigeyuki; Ishimoto, Yuyu; Yamada, Hiroshi; Takiguchi, Noboru; Nakagawa, Yukihiro; Minamide, Akihito; Oka, Hiroyuki; Kawaguchi, Hiroshi; Nakamura, Kozo; Akune, Toru; Yoshida, Munehito

2014-12-01

A narrow cervical spinal canal (CSC) is a well-known risk factor for cervical myelopathy (CM). However, no epidemiologic data of the CSC based on a population-based cohort are available. The purpose of the study was to investigate the age-related differences in CSC diameters on plain radiographs and to examine the associated magnetic resonance imaging (MRI) abnormalities including cervical cord compression and increased signal intensity (ISI) as well as the clinical CM with the narrow CSC. This was a cross-sectional study. Data were obtained from the baseline survey of the Wakayama Spine Study that was performed from 2008 to 2010 in a western part of Japan. Finally, a total of 959 subjects (319 men and 640 women; mean age, 66.4 years) were included. The outcome measures included in the study were the CSC diameter at C5 level on plain radiographs, cervical cord compression and ISI on sagittal T2-weighted MRI, and physical signs related to CM (eg, the Hoffmann reflex, hyperreflexia of the patellar tendon, the Babinski reflex, sensory and motor function, and bowel/bladder symptoms). The age-related differences of CSC diameters in men and women were investigated by descriptive statistics. The prevalence of MRI abnormalities and clinical CM was compared among the groups divided by the CSC diameter (less than 13, 13-15, and 15 mm or more). In addition, a logistic regression analysis was performed to determine the association of the CSC diameter with cervical cord compression/clinical CM after overall adjustment for age, sex, and body mass index. The CSC diameter was narrower with increasing age in both men and women. The prevalence of cervical cord compression, ISI, and the clinical CM was significantly higher in the narrower CSC group. The prevalence of cervical cord compression, ISI, and CM among subjects with CSC diameter less than 13 mm was 38.0%, 5.4%, and 10.1%, respectively. In the logistic model, the CSC diameter was a significant predictive factor for the clinical CM (p<.0001). This study firstly confirmed the age-related differences in CSC diameters and the significant association of the narrow CSC diameter with CM in a population-based cohort. Copyright © 2014 Elsevier Inc. All rights reserved.

Chemical Proteomic Approaches Targeting Cancer Stem Cells: A Review of Current Literature.

PubMed

Jung, Hye Jin

2017-01-01

Cancer stem cells (CSCs) have been proposed as central drivers of tumor initiation, progression, recurrence, and therapeutic resistance. Therefore, identifying stem-like cells within cancers and understanding their properties is crucial for the development of effective anticancer therapies. Recently, chemical proteomics has become a powerful tool to efficiently determine protein networks responsible for CSC pathophysiology and comprehensively elucidate molecular mechanisms of drug action against CSCs. This review provides an overview of major methodologies utilized in chemical proteomic approaches. In addition, recent successful chemical proteomic applications targeting CSCs are highlighted. Future direction of potential CSC research by integrating chemical genomic and proteomic data obtained from a single biological sample of CSCs are also suggested in this review. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Profile and programming needs of federal offenders with histories of intimate partner violence.

PubMed

Stewart, Lynn A; Power, Jenelle

2014-10-01

This study presents data on male perpetrators of domestic violence (DV) in the Correctional Service of Canada (CSC) using two samples: (a) a snapshot of all male offenders in CSC who had been assessed for DV (n = 15,166) and (b) a cumulative sample of male offenders in CSC from 2002-2010 who had been assessed as moderate or high risk for further DV (n = 4,261) DV offenders were compared to a cohort sample of non-DV offenders (n = 4,261). Analyses were disaggregated for Aboriginal and non-Aboriginal offenders. Results indicated that 40% of the federal male population had a suspected history of DV and were therefore screened in for in-depth DV risk assessment. Of these, 45% were assessed as moderate or high risk for future DV. DV offenders had higher risk and criminogenic need ratings, more learning disabilities, more mental health problems, and more extensive criminal histories than those without DV histories. Aboriginal DV offenders had high levels of alcohol dependence, suggesting a need for substance abuse treatment as part of DV programming. Most federal offenders with DV histories would be described as belonging to the Antisocial/Generalized Aggressive typology and, therefore, adhering to the Risk-Need-Responsivity principles of the effective correctional literature, cognitive-behavioral treatment that focuses on teaching skills of self-management, and changing attitudes supporting relationship violence would be recommended. © The Author(s) 2014.

Therapeutic potential of the metabolic modulator phenformin in targeting the stem cell compartment in melanoma.

PubMed

Petrachi, Tiziana; Romagnani, Alessandra; Albini, Adriana; Longo, Caterina; Argenziano, Giuseppe; Grisendi, Giulia; Dominici, Massimo; Ciarrocchi, Alessia; Dallaglio, Katiuscia

2017-01-24

Melanoma is the most dangerous and treatment-resistant skin cancer. Tumor resistance and recurrence are due to the persistence in the patient of aggressive cells with stem cell features, the cancer stem cells (CSC). Recent evidences have shown that CSC display a distinct metabolic profile as compared to tumor bulk population: a promising anti-tumor strategy is therefore to target specific metabolic pathways driving CSC behavior. Biguanides (metformin and phenformin) are anti-diabetic drugs able to perturb cellular metabolism and displaying anti-cancer activity. However, their ability to target the CSC compartment in melanoma is not known. Here we show that phenformin, but not metformin, strongly reduces melanoma cell viability, growth and invasion in both 2D and 3D (spheroids) models. While phenformin decreases melanoma CSC markers expression and the levels of the pro-survival factor MITF, MITF overexpression fails to prevent phenformin effects. Phenformin significantly reduces cell viability in melanoma by targeting both CSC (ALDHhigh) and non-CSC cells and by significantly reducing the number of viable cells in ALDHhigh and ALDHlow-derived spheroids. Consistently, phenformin reduces melanoma cell viability and growth independently from SOX2 levels. Our results show that phenformin is able to affect both CSC and non-CSC melanoma cell viability and growth and suggests its potential use as anti-cancer therapy in melanoma.

Therapeutic potential of the metabolic modulator phenformin in targeting the stem cell compartment in melanoma

PubMed Central

Albini, Adriana; Longo, Caterina; Argenziano, Giuseppe; Grisendi, Giulia; Dominici, Massimo; Ciarrocchi, Alessia; Dallaglio, Katiuscia

2017-01-01

Melanoma is the most dangerous and treatment-resistant skin cancer. Tumor resistance and recurrence are due to the persistence in the patient of aggressive cells with stem cell features, the cancer stem cells (CSC). Recent evidences have shown that CSC display a distinct metabolic profile as compared to tumor bulk population: a promising anti-tumor strategy is therefore to target specific metabolic pathways driving CSC behavior. Biguanides (metformin and phenformin) are anti-diabetic drugs able to perturb cellular metabolism and displaying anti-cancer activity. However, their ability to target the CSC compartment in melanoma is not known. Here we show that phenformin, but not metformin, strongly reduces melanoma cell viability, growth and invasion in both 2D and 3D (spheroids) models. While phenformin decreases melanoma CSC markers expression and the levels of the pro-survival factor MITF, MITF overexpression fails to prevent phenformin effects. Phenformin significantly reduces cell viability in melanoma by targeting both CSC (ALDHhigh) and non-CSC cells and by significantly reducing the number of viable cells in ALDHhigh and ALDHlow-derived spheroids. Consistently, phenformin reduces melanoma cell viability and growth independently from SOX2 levels. Our results show that phenformin is able to affect both CSC and non-CSC melanoma cell viability and growth and suggests its potential use as anti-cancer therapy in melanoma. PMID:28036292

Cancer Stem-like Cells Act via Distinct Signaling Pathways in Promoting Late Stages of Malignant Progression.

PubMed

da Silva-Diz, Victoria; Simón-Extremera, Pilar; Bernat-Peguera, Adrià; de Sostoa, Jana; Urpí, Maria; Penín, Rosa M; Sidelnikova, Diana Pérez; Bermejo, Oriol; Viñals, Joan Maria; Rodolosse, Annie; González-Suárez, Eva; Moruno, Antonio Gómez; Pujana, Miguel Ángel; Esteller, Manel; Villanueva, Alberto; Viñals, Francesc; Muñoz, Purificación

2016-03-01

Cancer stem-like cells (CSC) play key roles in long-term tumor propagation and metastasis, but their dynamics during disease progression are not understood. Tumor relapse in patients with initially excised skin squamous cell carcinomas (SCC) is characterized by increased metastatic potential, and SCC progression is associated with an expansion of CSC. Here, we used genetically and chemically-induced mouse models of skin SCC to investigate the signaling pathways contributing to CSC function during disease progression. We found that CSC regulatory mechanisms change in advanced SCC, correlating with aggressive tumor growth and enhanced metastasis. β-Catenin and EGFR signaling, induced in early SCC CSC, were downregulated in advanced SCC. Instead, autocrine FGFR1 and PDGFRα signaling, which have not been previously associated with skin SCC CSC, were upregulated in late CSC and promoted tumor growth and metastasis, respectively. Finally, high-grade and recurrent human skin SCC recapitulated the signaling changes observed in advanced mouse SCC. Collectively, our findings suggest a stage-specific switch in CSC regulation during disease progression that could be therapeutically exploited by targeting the PDGFR and FGFR1 pathways to block relapse and metastasis of advanced human skin SCC. ©2015 American Association for Cancer Research.

Optimization and Experimentation of Dual-Mass MEMS Gyroscope Quadrature Error Correction Methods

PubMed Central

Cao, Huiliang; Li, Hongsheng; Kou, Zhiwei; Shi, Yunbo; Tang, Jun; Ma, Zongmin; Shen, Chong; Liu, Jun

2016-01-01

This paper focuses on an optimal quadrature error correction method for the dual-mass MEMS gyroscope, in order to reduce the long term bias drift. It is known that the coupling stiffness and demodulation error are important elements causing bias drift. The coupling stiffness in dual-mass structures is analyzed. The experiment proves that the left and right masses’ quadrature errors are different, and the quadrature correction system should be arranged independently. The process leading to quadrature error is proposed, and the Charge Injecting Correction (CIC), Quadrature Force Correction (QFC) and Coupling Stiffness Correction (CSC) methods are introduced. The correction objects of these three methods are the quadrature error signal, force and the coupling stiffness, respectively. The three methods are investigated through control theory analysis, model simulation and circuit experiments, and the results support the theoretical analysis. The bias stability results based on CIC, QFC and CSC are 48 °/h, 9.9 °/h and 3.7 °/h, respectively, and this value is 38 °/h before quadrature error correction. The CSC method is proved to be the better method for quadrature correction, and it improves the Angle Random Walking (ARW) value, increasing it from 0.66 °/√h to 0.21 °/√h. The CSC system general test results show that it works well across the full temperature range, and the bias stabilities of the six groups’ output data are 3.8 °/h, 3.6 °/h, 3.4 °/h, 3.1 °/h, 3.0 °/h and 4.2 °/h, respectively, which proves the system has excellent repeatability. PMID:26751455

Optimization and Experimentation of Dual-Mass MEMS Gyroscope Quadrature Error Correction Methods.

PubMed

Cao, Huiliang; Li, Hongsheng; Kou, Zhiwei; Shi, Yunbo; Tang, Jun; Ma, Zongmin; Shen, Chong; Liu, Jun

2016-01-07

This paper focuses on an optimal quadrature error correction method for the dual-mass MEMS gyroscope, in order to reduce the long term bias drift. It is known that the coupling stiffness and demodulation error are important elements causing bias drift. The coupling stiffness in dual-mass structures is analyzed. The experiment proves that the left and right masses' quadrature errors are different, and the quadrature correction system should be arranged independently. The process leading to quadrature error is proposed, and the Charge Injecting Correction (CIC), Quadrature Force Correction (QFC) and Coupling Stiffness Correction (CSC) methods are introduced. The correction objects of these three methods are the quadrature error signal, force and the coupling stiffness, respectively. The three methods are investigated through control theory analysis, model simulation and circuit experiments, and the results support the theoretical analysis. The bias stability results based on CIC, QFC and CSC are 48 °/h, 9.9 °/h and 3.7 °/h, respectively, and this value is 38 °/h before quadrature error correction. The CSC method is proved to be the better method for quadrature correction, and it improves the Angle Random Walking (ARW) value, increasing it from 0.66 °/√h to 0.21 °/√h. The CSC system general test results show that it works well across the full temperature range, and the bias stabilities of the six groups' output data are 3.8 °/h, 3.6 °/h, 3.4 °/h, 3.1 °/h, 3.0 °/h and 4.2 °/h, respectively, which proves the system has excellent repeatability.

76 FR 14678 - Communications Unit Leader Prerequisite and Evaluation

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-17

... DEPARTMENT OF HOMELAND SECURITY [Docket No. DHS-2010-0004] Communications Unit Leader Prerequisite... Security (DHS), National Protection and Programs Directorate (NPPD), Cybersecurity and Communications (CS&C), Office of Emergency Communications (OEC) will submit the following information collection request to the...

76 FR 7870 - Agency Information Collection Activities: Cybersecurity and Communications Technical Assistance...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-11

... DEPARTMENT OF HOMELAND SECURITY [Docket No. DHS-2010-0006] Agency Information Collection Activities: Cybersecurity and Communications Technical Assistance Request and Evaluation AGENCY: National... Programs Directorate (NPPD), Office of Cybersecurity and Communications (CS&C), Office of Emergency...

A review of CARE’s Community Score Card experience and evidence

PubMed Central

Gullo, Sara; Galavotti, Christine; Altman, Lara

2016-01-01

The global community’s growing enthusiasm for the potential of social accountability approaches to improve health system performance and accelerate health progress makes it imperative that we learn from social accountability intervention implementation experience and results. To this end, we carried out a review of Cooperative for Assistance and Relief Everywhere, Inc. (CARE)’s experience with the Community Score Card© (CSC)—a social accountability approach CARE developed in Malawi. We reviewed projects that CARE implemented between 2002 and 2013 that employed the CSC and that had at least one evaluation in English. We systematically collected and synthesized information from evaluations on the projects’ characteristics, CSC-related outcomes and challenges. Eight projects, spanning five countries, met our inclusion criteria. The projects applied the CSC to various focus areas, mostly health. We identified one to three evaluations, mostly qualitative, for each project. While the evaluations had many limitations, consistency of the results, as well as the range of outcomes, suggests that the CSC is contributing to significant changes. All projects reported CSC-related governance outcomes and service outcomes. There is promising evidence that the CSC can contribute to citizen empowerment, service provider and power-holder effectiveness, accountability and responsiveness and spaces for negotiation between the two that are expanded, effective and inclusive. There is also evidence that the CSC may contribute to improvements in service availability, access, utilization and quality. The CSC seems particularly suited to building trust and strengthening relationships between the community and service providers and to improving the user-centred dimension of quality. All of the projects reported challenges, with ensuring national responsiveness and inclusion of marginalized groups in the CSC process proving to be the most intractable. To improve health system performance and accelerate health progress we recommend further CSC use, enhancements and research. PMID:27190223

En face choroidal vascular feature imaging in acute and chronic central serous chorioretinopathy using swept source optical coherence tomography.

PubMed

Lee, Won June; Lee, Jung Wook; Park, Seung Hun; Lee, Byung Ro

2017-05-01

To evaluate the variable depth tomographic features of choroidal vasculature in acute and chronic central serous chorioretinopathy (CSC) using swept source optical coherence tomography (SS-OCT) en face imaging. We retrospectively reviewed the en face SS-OCT images of 29 patients that presented with acute (12 eyes) or chronic (17 eyes) CSC. All of the patient eyes underwent 6×6 macular scans with SS-OCT (DRI OCT-1, Topcon, Tokyo, Japan), fluorescein angiography and indocyanine green angiography. The en face image was used to investigate the choroidal vasculature of each layer. Moreover, we determined that some parts corresponded to choriocapillaris and Sattler's layer attenuation, whereas choroidal vessel dilatation was associated with Haller's layer. At Haller's layer level, choroidal vessel dilatation was observed in 11 of 12 acute CSC (91.7%) and 15 of 17 chronic CSC (88.2%). In acute CSC, choroidal vessel dilatation was divided into focal (9/11; 81.8%) and diffuse (2/11; 18.2%) patterns. The chronic CSC cases demonstrated different patterns of choroidal vessel dilatation: focal (5/15; 33.3%) and diffuse (10/15; 66.6%). Ten of the acute CSC eyes (83.3%) and 14 of the chronic CSC eyes (82.4%) were found to have obscured choriocapillaris and Sattler's layers on en face imaging. En face imaging of SS-OCT is useful when combined with angiography in CSC for evaluating choroidal vessel dilatation at Haller's layer and to identify obscured upper layers. We identified different choroidal vessel dilatation patterns between acute and chronic CSC. These findings might be useful for pathophysiological understanding of CSC. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Testicular cells exhibit similar molecular responses to cigarette smoke condensate ex vivo and in vivo.

PubMed

Esakky, Prabagaran; Hansen, Deborah A; Drury, Andrea M; Felder, Paul; Cusumano, Andrew; Moley, Kelle H

2018-01-01

Male exposure to cigarette smoke is associated with seminal defects and with congenital anomalies and childhood cancers in offspring. In mice, paternal exposure to cigarette smoke condensate (CSC) causes molecular defects in germ cells and phenotypic effects in their offspring. Here we used an ex vivo testicular explant model and in vivo exposure to determine the concentration at which CSC impairs spermatogenesis and offspring development. We explanted testis tissue at postnatal day (P)5.5 and cultured it until P11.5. Assessment of growth parameters by analyzing expression of cell-specific markers revealed that the explant system maintained structural and functional integrity. We exposed the P5.5 to -11.5 explants to various concentrations (40-160 µg/ml) of CSC and confirmed that nicotine in the CSC was metabolized to cotinine. We assessed various growth and differentiation parameters, as well as testosterone production, and observed that many spermatogenesis features were impaired at 160 µg/ml CSC. The same parameters were impaired by a similar CSC concentration in vivo Finally, females mated to males that were exposed to 160 µg/ml CSC neonatally had increased rates of pup resorption. We conclude that male exposure to CSC impairs offspring development and that the concentration at which CSC impairs spermatogenesis is similar in vivo and ex vivo. Given that the concentrations of CSC we used contained similar doses of nicotine as human smokers are exposed to, we argue that our model mimics human male reproductive effects of smoking.-Esakky, P., Hansen, D. A., Drury, A. M., Felder, P., Cusumano, A., Moley, K. H. Testicular cells exhibit similar molecular responses to cigarette smoke condensate ex vivo and in vivo . © FASEB.

A review on the mechanism, risk evaluation, and prevention of coal spontaneous combustion in China.

PubMed

Kong, Biao; Li, Zenghua; Yang, Yongliang; Liu, Zhen; Yan, Daocheng

2017-10-01

In recent years, the ecology, security, and sustainable development of modern mines have become the theme of coal mine development worldwide. However, spontaneous combustion of coal under conditions of oxygen supply and automatic exothermic heating during coal mining lead to coalfield fires. Coal spontaneous combustion (CSC) causes huge economic losses and casualties, with the toxic and harmful gases produced during coal combustion not only polluting the working environment, but also causing great damage to the ecological environment. China is the world's largest coal producer and consumer; however, coal production in Chinese mines is seriously threatened by the CSC risk. Because deep underground mining methods are commonly adopted in Chinese coal mines, coupling disasters are frequent in these mines with the coalfield fires becoming increasingly serious. Therefore, in this study, we analyzed the development mechanism of CSC. The CSC risk assessment was performed from the aspects of prediction, detection, and determination of the "dangerous area" in a coal mine (i.e., the area most susceptible to fire hazards). A new geophysical method for CSC determination is proposed and analyzed. Furthermore, the main methods for CSC fire prevention and control and their advantages and disadvantages are analyzed. To eventually construct CSC prevention and control integration system, future developmental direction of CSC was given from five aspects. Our results can present a reference for the development of CSC fire prevention and control technology and promote the protection of ecological environment in China.

S-Acylation of the cellulose synthase complex is essential for its plasma membrane localization.

PubMed

Kumar, Manoj; Wightman, Raymond; Atanassov, Ivan; Gupta, Anjali; Hurst, Charlotte H; Hemsley, Piers A; Turner, Simon

2016-07-08

Plant cellulose microfibrils are synthesized by a process that propels the cellulose synthase complex (CSC) through the plane of the plasma membrane. How interactions between membranes and the CSC are regulated is currently unknown. Here, we demonstrate that all catalytic subunits of the CSC, known as cellulose synthase A (CESA) proteins, are S-acylated. Analysis of Arabidopsis CESA7 reveals four cysteines in variable region 2 (VR2) and two cysteines at the carboxy terminus (CT) as S-acylation sites. Mutating both the VR2 and CT cysteines permits CSC assembly and trafficking to the Golgi but prevents localization to the plasma membrane. Estimates suggest that a single CSC contains more than 100 S-acyl groups, which greatly increase the hydrophobic nature of the CSC and likely influence its immediate membrane environment. Copyright © 2016, American Association for the Advancement of Science.

41 CFR 101-28.306-5 - Safeguards.

Code of Federal Regulations, 2011 CFR

2011-07-01

... these access codes that orders are accepted by the CSC and these codes determine the ship-to points for all orders filled by the CSC with the exception of orders picked up at the CSC by the customer. GSA...

41 CFR 101-28.306-5 - Safeguards.

Code of Federal Regulations, 2010 CFR

2010-07-01

... these access codes that orders are accepted by the CSC and these codes determine the ship-to points for all orders filled by the CSC with the exception of orders picked up at the CSC by the customer. GSA...

Short-term efficacy of intravitreal dobesilate in central serous chorioretinopathy

PubMed Central

2012-01-01

Purpose To report the anatomic and functional outcome of intravitreal dobesilate to treat recurrent central serous chorioretinopathy (CSC). Methods This is an interventional case report in which dobesilate was intravitreally injected in a case of recurrent CSC. Main measures included fundoscopy, Snellen visual acuity (VA) testing, fluorescein angiography and optical coherence tomography (OCT). Results We present anatomical and functional evidences, obtained as early as eleven days after the treatment, of the efficacy of intravitreal dobesilate, in the treatment of chronic CSC condition. The effect after intravitreal dobesilate injection for CSC might be related to the normalization of retinal architecture. Conclusions Intravitreal dobesilate may be an effective treatment option for recurrent CSC. PMID:22788836

Susceptibility to cytotoxic T cell lysis of cancer stem cells derived from cervical and head and neck tumor cell lines.

PubMed

Liao, Tian; Kaufmann, Andreas M; Qian, Xu; Sangvatanakul, Voramon; Chen, Chao; Kube, Tina; Zhang, Guoyou; Albers, Andreas E

2013-01-01

To explore cancer stem cell susceptibility to a host's cytotoxic T lymphocyte (CTL)-mediated immune response. We compared the susceptibility of putative CSC generated from cancer cell lines to immunologic recognition and killing by alloantigen-specific CD8(+) CTL. CSC-enriched spheroid culture-derived cells (SDC) exhibited higher expression of ALDH, ICAM1 and of stem/progenitor cell markers on all 3 tumor cell lines investigated and lower MHC class I on the cervical cancer cell line as compared to their monolayer-derived cells (MDC). The expression of ICAM1 and MHCI was upregulated by IFN-γ treatment. CSC populations were less sensitive to MHC class I-restricted alloantigen-specific CD8(+) CTL lysis as compared to matched MDC. IFN-γ pretreatment resulted in over-proportionally enhanced lysis of SDC. Finally, the subset of ALDH(high) expressing SDC presented more sensitivity toward CD8(+) CTL killing than the ALDH(low) SDC. Tumor therapy resistance has been attributed to cancer stem cells (CSC). We show in vitro susceptibility of CSC to CTL-mediated lysis. Immunotherapy targeting of ALDH(+) CSC may therefore be a promising approach. Our results and method may be helpful for the development and optimization of adjuvants, as here exemplified for INF-γ, for CSC-targeted vaccines, independent of the availability of CSC-specific antigens.

The Chandra Source Catalog 2.0: Interfaces

NASA Astrophysics Data System (ADS)

D'Abrusco, Raffaele; Zografou, Panagoula; Tibbetts, Michael; Allen, Christopher E.; Anderson, Craig S.; Budynkiewicz, Jamie A.; Burke, Douglas; Chen, Judy C.; Civano, Francesca Maria; Doe, Stephen M.; Evans, Ian N.; Evans, Janet D.; Fabbiano, Giuseppina; Gibbs, Danny G., II; Glotfelty, Kenny J.; Graessle, Dale E.; Grier, John D.; Hain, Roger; Hall, Diane M.; Harbo, Peter N.; Houck, John C.; Lauer, Jennifer L.; Laurino, Omar; Lee, Nicholas P.; Martínez-Galarza, Rafael; McCollough, Michael L.; McDowell, Jonathan C.; Miller, Joseph; McLaughlin, Warren; Morgan, Douglas L.; Mossman, Amy E.; Nguyen, Dan T.; Nichols, Joy S.; Nowak, Michael A.; Paxson, Charles; Plummer, David A.; Primini, Francis Anthony; Rots, Arnold H.; Siemiginowska, Aneta; Sundheim, Beth A.; Van Stone, David W.

2018-01-01

Easy-to-use, powerful public interfaces to access the wealth of information contained in any modern, complex astronomical catalog are fundamental to encourage its usage. In this poster,I present the public interfaces of the second Chandra Source Catalog (CSC2). CSC2 is the most comprehensive catalog of X-ray sources detected by Chandra, thanks to the inclusion of Chandra observations public through the end of 2014 and to methodological advancements. CSC2 provides measured properties for a large number of sources that sample the X-ray sky at fainter levels than the previous versions of the CSC, thanks to the stacking of single overlapping observations within 1’ before source detection. Sources from stacks are then crossmatched, if multiple stacks cover the same area of the sky, to create a list of unique, optimal CSC2 sources. The properties of sources detected in each single stack and each single observation are also measured. The layered structure of the CSC2 catalog is mirrored in the organization of the CSC2 database, consisting of three tables containing all properties for the unique stacked sources (“Master Source”), single stack sources (“Stack Source”) and sources in any single observation (“Observation Source”). These tables contain estimates of the position, flags, extent, significances, fluxes, spectral properties and variability (and associated errors) for all classes of sources. The CSC2 also includes source region and full-field data products for all master sources, stack sources and observation sources: images, photon event lists, light curves and spectra.CSCview, the main interface to the CSC2 source properties and data products, is a GUI tool that allows to build queries based on the values of all properties contained in CSC2 tables, query the catalog, inspect the returned table of source properties, browse and download the associated data products. I will also introduce the suite of command-line interfaces to CSC2 that can be used in alternative to CSCview, and will present the concept for an additional planned cone-search web-based interface.This work has been supported by NASA under contract NAS 8-03060 to the Smithsonian Astrophysical Observatory for operation of the Chandra X-ray Center.

Chandra Source Catalog: User Interfaces

NASA Astrophysics Data System (ADS)

Bonaventura, Nina; Evans, I. N.; Harbo, P. N.; Rots, A. H.; Tibbetts, M. S.; Van Stone, D. W.; Zografou, P.; Anderson, C. S.; Chen, J. C.; Davis, J. E.; Doe, S. M.; Evans, J. D.; Fabbiano, G.; Galle, E.; Gibbs, D. G.; Glotfelty, K. J.; Grier, J. D.; Hain, R.; Hall, D. M.; He, X.; Houck, J. C.; Karovska, M.; Lauer, J.; McCollough, M. L.; McDowell, J. C.; Miller, J. B.; Mitschang, A. W.; Morgan, D. L.; Nichols, J. S.; Nowak, M. A.; Plummer, D. A.; Primini, F. A.; Refsdal, B. L.; Siemiginowska, A. L.; Sundheim, B. A.; Winkelman, S. L.

2010-03-01

The CSCview data mining interface is available for browsing the Chandra Source Catalog (CSC) and downloading tables of quality-assured source properties and data products. Once the desired source properties and search criteria are entered into the CSCview query form, the resulting source matches are returned in a table along with the values of the requested source properties for each source. (The catalog can be searched on any source property, not just position.) At this point, the table of search results may be saved to a text file, and the available data products for each source may be downloaded. CSCview save files are output in RDB-like and VOTable format. The available CSC data products include event files, spectra, lightcurves, and images, all of which are processed with the CIAO software. CSC data may also be accessed non-interactively with Unix command-line tools such as cURL and Wget, using ADQL 2.0 query syntax. In fact, CSCview features a separate ADQL query form for those who wish to specify this type of query within the GUI. Several interfaces are available for learning if a source is included in the catalog (in addition to CSCview): 1) the CSC interface to Sky in Google Earth shows the footprint of each Chandra observation on the sky, along with the CSC footprint for comparison (CSC source properties are also accessible when a source within a Chandra field-of-view is clicked); 2) the CSC Limiting Sensitivity online tool indicates if a source at an input celestial location was too faint for detection; 3) an IVOA Simple Cone Search interface locates all CSC sources within a specified radius of an R.A. and Dec.; and 4) the CSC-SDSS cross-match service returns the list of sources common to the CSC and SDSS, either all such sources or a subset based on search criteria.

NW CSC annual report fiscal year 2013

USGS Publications Warehouse

Bisbal, Gustavo A.

2013-01-01

The Northwest Climate Science Center (NW CSC) was established in 2010 as one of eight regional Climate Science Centers created by the Department of the Interior (DOI). The NW CSC encompasses Washing-ton, Oregon, Idaho, and western Montana and has overlapping boundaries with three Landscape Conservation Cooperatives (LCCs): the Great Northern, the Great Basin, and the North Pacific. With guidance from its Executive Stakeholder Advisory Committee (ESAC), the NW CSC and its partner LCCs are addressing the highest priority regional climate science needs of Northwest natural and cultural resource managers. Climate Science Centers tap into the scientific expertise of both the U.S. Geological Survey (USGS) and academic institutions. The NW CSC is supported by an academic consortium with the capacity to generate climate science and tools in a coordinated fashion, serving stakeholders across the Northwest region. This consortium is primarily represented by Oregon State University (OSU), the University of Id-ho (UI), and the University of Washington (UW). The academic consortium and USGS provide capabilities in climate science, ecology, impacts and vulnerability assessment, modeling, adaptation planning, and advanced information technology, all necessary to address and respond to climate change in the Northwest. University members also recruit and train graduate students and early-career scientists. This Annual Report summarizes progress for the goals set out in the NW CSC Strategic Plan for 2012-2015 (http://www.doi.gov/csc/northwest/upload/Northwest-CSC-Strategic-Plan.cfm) and the NW CSC Work-plan for Fiscal Year (FY) 2013 (October 1, 2012 through September 30, 2013). The report follows the structure of the Strategic Plan, which describes the five core services (Executive, Science, Data, Communications, and Education and Training) provided by the NW CSC in support of the stated vision: Our Vision: To become nationally recognized as a best-practice model for the provision of climate science and decision support tools to address conservation and management issues in the Pacific Northwest Region.

Cell division patterns and chromosomal segregation defects in oral cancer stem cells.

PubMed

Kaseb, Hatem O; Lewis, Dale W; Saunders, William S; Gollin, Susanne M

2016-09-01

Oral squamous cell carcinoma (OSCC) is a serious public health problem caused primarily by smoking and alcohol consumption or human papillomavirus. The cancer stem cell (CSC) theory posits that CSCs show unique characteristics, including self-renewal and therapeutic resistance. Examining biomarkers and other features of CSCs is critical to better understanding their biology. To this end, the results show that cellular SOX2 immunostaining correlates with other CSC biomarkers in OSCC cell lines and marks the rare CSC population. To assess whether CSC division patterns are symmetrical, resulting in two CSC, or asymmetrical, leading to one CSC and one cancer cell, cell size and fluorescence intensity of mitotic cells stained with SOX2 were analyzed. Asymmetrical SOX2 distribution in ≈25% of the mitoses analyzed was detected. Chromosomal instability, some of which is caused by chromosome segregation defects (CSDs), is a feature of cancer cells that leads to altered gene copy numbers. We compare chromosomal instability (as measured by CSDs) between CSCs (SOX2+) and non-CSCs (SOX2-) from the same OSCC cell lines. CSDs were more common in non-CSCs (SOX2-) than CSCs (SOX2+) and in symmetrical CSC (SOX2+) mitotic pairs than asymmetrical CSC (SOX2+/SOX2-) mitotic pairs. CSCs showed fewer and different types of CSDs after ionizing radiation treatment than non-CSCs. Overall, these data are the first to demonstrate both symmetrical and asymmetrical cell divisions with CSDs in OSCC CSC. Further, the results suggest that CSCs may undergo altered behavior, including therapeutic resistance as a result of chromosomal instability due to chromosome segregation defects. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Characterization of cancer stem cell properties of CD24 and CD26-positive human malignant mesothelioma cells

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

Yamazaki, Hiroto; Naito, Motohiko; Ghani, Farhana Ishrat

2012-03-16

Highlights: Black-Right-Pointing-Pointer We focused on CD24 and CD26 for further analysis of CSC properties in MM. Black-Right-Pointing-Pointer Their expressions were correlated with chemoresistance, cell growth, and invasion. Black-Right-Pointing-Pointer Their expressions were also correlated with several cancer related genes. Black-Right-Pointing-Pointer The expression of each marker was correlated with different CSC property in Meso1. Black-Right-Pointing-Pointer Phosphorylation of ERK by EGF was regulated by expression of CD26, but not CD24. -- Abstract: Malignant mesothelioma (MM) is an asbestos-related malignancy characterized by rapid growth and poor prognosis. In our previous study, we have demonstrated that several cancer stem cell (CSC) markers correlated with CSCmore » properties in MM cells. Among these markers, we focused on two: CD24, the common CSC marker, and CD26, the additional CSC marker. We further analyzed the CSC properties of CD24 and CD26-positve MM cells. We established RNAi-knockdown cells and found that these markers were significantly correlated with chemoresistance, proliferation, and invasion potentials in vitro. Interestingly, while Meso-1 cells expressed both CD24 and CD26, the presence of each of these two markers was correlated with different CSC property. In addition, downstream signaling of these markers was explored by microarray analysis, which revealed that their expressions were correlated with several cancer-related genes. Furthermore, phosphorylation of ERK by EGF stimulation was significantly affected by the expression of CD26, but not CD24. These results suggest that CD24 and CD26 differentially regulate the CSC potentials of MM and could be promising targets for CSC-oriented therapy.« less

DNA adduct formation in mice following dermal application of smoke condensates from cigarettes that burn or heat tobacco

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

Lee, C.K.; Brown, B.G.; Reed, E.A.

A prototype cigarette that heats tobacco (test cigarette), developed by R.J. Reynolds Tobacco Company, has yielded consistently negative results in several in vivo and in vitro genetic toxicology tests. The objective of the present study was to evaluate the potential of cigarette smoke condensate (CSC) from the test cigarette to induce DNA adducts in mouse tissues and compare the results with those obtained with CSC from a reference tobacco-burning cigarette (1R4F). CD-1 mice were skin-painted with CSF from reference and test cigarettes three times a week for 4 weeks. The highest mass of CSC applied was 180 mg tar permore » week per animal for both reference and test cigarette. DNA adducts were analyzed in skin and lung tissues using the [sup 32]P-postlabeling method with the P[sub 1] nuclease modification. Distinct diagonal radioactive zones (DRZ) were observed in the DNA from both skin and lung tissues of animals dosed with reference CSC, whereas no corresponding DRZ were observed from the DNA of animals dosed with either test CSC or acetone (solvent control). The relative adduct labeling (RAL) values of skin and lung DNA from reference CSC-treated animals were significantly greater than those of the test CSC-treated animals. The RAL values of the test CSC-treated animals were no greater than those of solvent controls. The negative results in DNA adduct assays with test CSC are consistent with all previous results of in vivo and in vitro genetic toxicology testing on this cigarette and provide additional evidence that smoke condensate from the test cigarette is not genotoxic. 31 refs., 4 figs., 2 tabs.« less

CD10-/ALDH- cells are the sole cisplatin-resistant component of a novel ovarian cancer stem cell hierarchy.

PubMed

Ffrench, Brendan; Gasch, Claudia; Hokamp, Karsten; Spillane, Cathy; Blackshields, Gordon; Mahgoub, Thamir Mahmoud; Bates, Mark; Kehoe, Louise; Mooney, Aoibhinn; Doyle, Ronan; Doyle, Brendan; O'Donnell, Dearbhaile; Gleeson, Noreen; Hennessy, Bryan T; Stordal, Britta; O'Riain, Ciaran; Lambkin, Helen; O'Toole, Sharon; O'Leary, John J; Gallagher, Michael F

2017-10-19

It is long established that tumour-initiating cancer stem cells (CSCs) possess chemoresistant properties. However, little is known of the mechanisms involved, particularly with respect to the organisation of CSCs as stem-progenitor-differentiated cell hierarchies. Here we aimed to elucidate the relationship between CSC hierarchies and chemoresistance in an ovarian cancer model. Using a single cell-based approach to CSC discovery and validation, we report a novel, four-component CSC hierarchy based around the markers cluster of differentiation 10 (CD10) and aldehyde dehydrogenase (ALDH). In a change to our understanding of CSC biology, resistance to chemotherapy drug cisplatin was found to be the sole property of CD10 - /ALDH - CSCs, while all four CSC types were sensitive to chemotherapy drug paclitaxel. Cisplatin treatment quickly altered the hierarchy, resulting in a three-component hierarchy dominated by the cisplatin-resistant CD10 - /ALDH - CSC. This organisation was found to be hard-wired in a long-term cisplatin-adapted model, where again CD10 - /ALDH - CSCs were the sole cisplatin-resistant component, and all CSC types remained paclitaxel-sensitive. Molecular analysis indicated that cisplatin resistance is associated with inherent- and adaptive-specific drug efflux and DNA-damage repair mechanisms. Clinically, low CD10 expression was consistent with a specific set of ovarian cancer patient samples. Collectively, these data advance our understanding of the relationship between CSC hierarchies and chemoresistance, which was shown to be CSC- and drug-type specific, and facilitated by specific and synergistic inherent and adaptive mechanisms. Furthermore, our data indicate that primary stage targeting of CD10 - /ALDH - CSCs in specific ovarian cancer patients in future may facilitate targeting of recurrent disease, before it ever develops.

Analysis of the color alteration and radiopacity promoted by bismuth oxide in calcium silicate cement.

PubMed

Marciano, Marina Angélica; Estrela, Carlos; Mondelli, Rafael Francisco Lia; Ordinola-Zapata, Ronald; Duarte, Marco Antonio Hungaro

2013-01-01

The aim of the study was to determine if the increase in radiopacity provided by bismuth oxide is related to the color alteration of calcium silicate-based cement. Calcium silicate cement (CSC) was mixed with 0%, 15%, 20%, 30% and 50% of bismuth oxide (BO), determined by weight. Mineral trioxide aggregate (MTA) was the control group. The radiopacity test was performed according to ISO 6876/2001. The color was evaluated using the CIE system. The assessments were performed after 24 hours, 7 and 30 days of setting time, using a spectrophotometer to obtain the ΔE, Δa, Δb and ΔL values. The statistical analyses were performed using the Kruskal-Wallis/Dunn and ANOVA/Tukey tests (p<0.05). The cements in which bismuth oxide was added showed radiopacity corresponding to the ISO recommendations (>3 mm equivalent of Al). The MTA group was statistically similar to the CSC/30% BO group (p>0.05). In regard to color, the increase of bismuth oxide resulted in a decrease in the ΔE value of the calcium silicate cement. The CSC group presented statistically higher ΔE values than the CSC/50% BO group (p<0.05). The comparison between 24 hours and 7 days showed higher ΔE for the MTA group, with statistical differences for the CSC/15% BO and CSC/50% BO groups (p<0.05). After 30 days, CSC showed statistically higher ΔE values than CSC/30% BO and CSC/50% BO (p<0.05). In conclusion, the increase in radiopacity provided by bismuth oxide has no relation to the color alteration of calcium silicate-based cements.

Central serous chorioretinopathy treatment with spironolactone: a challenge-rechallenge case.

PubMed

Ryan, Edwin H; Pulido, Christine M

2015-01-01

To present a case of central serous chorioretinopathy (CSC) treatment with spironolactone in a challenge-rechallenge pattern. At presentation, fundus photography, fluorescein angiography, spectral domain optical coherence tomography, and enhanced depth imaging ocular coherence tomography were performed in both eyes. The patient was prescribed 25 mg spironolactone daily along with serum potassium monitoring. At follow-ups, spectral domain optical coherence tomography and enhanced depth imaging ocular coherence tomography were performed. A 37-year-old white male accountant presenting with CSC. Spironolactone treatment resolved the CSC. After the patient discontinued treatment, it returned. After returning to daily treatment, the CSC again resolved. Spironolactone was an effective treatment of CSC in this case. Other groups have reported similar findings with eplerenone, a similar drug.

NASA's Commercial Space Centers: Bringing Together Government and Industry for "Out of this World" Benefits

NASA Technical Reports Server (NTRS)

Robinson, R. Keith; Henderson, Robin N. (Technical Monitor)

2002-01-01

The National Aeronautics and Space Administration (NASA) is making significant effort to accommodate commercial research in the utilization plans of the International Space Station (ISS)[1]. NASA is providing 30% of the research accommodations in the ISS laboratory modules to support commercial endeavors. However, the availability of resources alone does not necessarily translate into significant private sector participation in NASA's ISS utilization plans. Due to the efforts of NASA's Commercial Space Centers (CSC's), NASA has developed a very robust plan for involving the private sector in ISS utilization activities. Obtaining participation from the private sector requires a demonstrated capability for obtaining commercially significant research results. Since 1985, NASA CSC's have conducted over 200 commercial research activities aboard parabolic aircraft, sounding rockets, the Space Shuttle, and the ISS. The success of these activities has developed substantial investment from private sector companies in commercial space research.

Fucosylation is a common glycosylation type in pancreatic cancer stem cell-like phenotypes.

PubMed

Terao, Naoko; Takamatsu, Shinji; Minehira, Tomomi; Sobajima, Tomoaki; Nakayama, Kotarosumitomo; Kamada, Yoshihiro; Miyoshi, Eiji

2015-04-07

To evaluate/isolate cancer stem cells (CSCs) from tissue or cell lines according to various definitions and cell surface markers. Lectin microarray analysis was conducted on CSC-like fractions of the human pancreatic cancer cell line Panc1 by establishing anti-cancer drug-resistant cells. Changes in glycan structure of CSC-like cells were also investigated in sphere-forming cells as well as in CSC fractions obtained from overexpression of CD24 and CD44. Several types of fucosylation were increased under these conditions, and the expression of fucosylation regulatory genes such as fucosyltransferases, GDP-fucose synthetic enzymes, and GDP-fucose transporters were dramatically enhanced in CSC-like cells. These changes were significant in gemcitabine-resistant cells and sphere cells of a human pancreatic cancer cell line, Panc1. However, downregulation of cellular fucosylation by knockdown of the GDP-fucose transporter did not alter gemcitabine resistance, indicating that increased cellular fucosylation is a result of CSC-like transformation. Fucosylation might be a biomarker of CSC-like cells in pancreatic cancer.

Comparative structural and computational analysis supports eighteen cellulose synthases in the plant cellulose synthesis complex

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

Nixon, B. Tracy; Mansouri, Katayoun; Singh, Abhishek

A six-lobed membrane spanning cellulose synthesis complex (CSC) containing multiple cellulose synthase (CESA) glycosyltransferases mediates cellulose microfibril formation. The number of CESAs in the CSC has been debated for decades in light of changing estimates of the diameter of the smallest microfibril formed from the β-1,4 glucan chains synthesized by one CSC. We obtained more direct evidence through generating improved transmission electron microscopy (TEM) images and image averages of the rosette-type CSC, revealing the frequent triangularity and average cross-sectional area in the plasma membrane of its individual lobes. Trimeric oligomers of two alternative CESA computational models corresponded well with individualmore » lobe geometry. A six-fold assembly of the trimeric computational oligomer had the lowest potential energy per monomer and was consistent with rosette CSC morphology. Negative stain TEM and image averaging showed the triangularity of a recombinant CESA cytosolic domain, consistent with previous modeling of its trimeric nature from small angle scattering (SAXS) data. Six trimeric SAXS models nearly filled the space below an average FF-TEM image of the rosette CSC. In conclusion, the multifaceted data support a rosette CSC with 18 CESAs that mediates the synthesis of a fundamental microfibril composed of 18 glucan chains.« less

Comparative structural and computational analysis supports eighteen cellulose synthases in the plant cellulose synthesis complex

DOE PAGES

Nixon, B. Tracy; Mansouri, Katayoun; Singh, Abhishek; ...

2016-06-27

A six-lobed membrane spanning cellulose synthesis complex (CSC) containing multiple cellulose synthase (CESA) glycosyltransferases mediates cellulose microfibril formation. The number of CESAs in the CSC has been debated for decades in light of changing estimates of the diameter of the smallest microfibril formed from the β-1,4 glucan chains synthesized by one CSC. We obtained more direct evidence through generating improved transmission electron microscopy (TEM) images and image averages of the rosette-type CSC, revealing the frequent triangularity and average cross-sectional area in the plasma membrane of its individual lobes. Trimeric oligomers of two alternative CESA computational models corresponded well with individualmore » lobe geometry. A six-fold assembly of the trimeric computational oligomer had the lowest potential energy per monomer and was consistent with rosette CSC morphology. Negative stain TEM and image averaging showed the triangularity of a recombinant CESA cytosolic domain, consistent with previous modeling of its trimeric nature from small angle scattering (SAXS) data. Six trimeric SAXS models nearly filled the space below an average FF-TEM image of the rosette CSC. In conclusion, the multifaceted data support a rosette CSC with 18 CESAs that mediates the synthesis of a fundamental microfibril composed of 18 glucan chains.« less

Bone marrow-derived fibrocytes promote stem cell-like properties of lung cancer cells.

PubMed

Saijo, Atsuro; Goto, Hisatsugu; Nakano, Mayuri; Mitsuhashi, Atsushi; Aono, Yoshinori; Hanibuchi, Masaki; Ogawa, Hirohisa; Uehara, Hisanori; Kondo, Kazuya; Nishioka, Yasuhiko

2018-05-01

Cancer stem cells (CSCs) represent a minor population that have clonal tumor initiation and self-renewal capacity and are responsible for tumor initiation, metastasis, and therapeutic resistance. CSCs reside in niches, which are composed of diverse types of stromal cells and extracellular matrix components. These stromal cells regulate CSC-like properties by providing secreted factors or by physical contact. Fibrocytes are differentiated from bone marrow-derived CD14 + monocytes and have features of both macrophages and fibroblasts. Accumulating evidence has suggested that stromal fibrocytes might promote cancer progression. However, the role of fibrocytes in the CSC niches has not been revealed. We herein report that human fibrocytes enhanced the CSC-like properties of lung cancer cells through secreted factors, including osteopontin, CC-chemokine ligand 18, and plasminogen activator inhibitor-1. The PIK3K/AKT pathway was critical for fibrocytes to mediate the CSC-like functions of lung cancer cells. In human lung cancer specimens, the number of tumor-infiltrated fibrocytes was correlated with high expression of CSC-associated protein in cancer cells. These results suggest that fibrocytes may be a novel cell population that regulates the CSC-like properties of lung cancer cells in the CSC niches. Copyright © 2018. Published by Elsevier B.V.

Comparative Structural and Computational Analysis Supports Eighteen Cellulose Synthases in the Plant Cellulose Synthesis Complex

PubMed Central

Nixon, B. Tracy; Mansouri, Katayoun; Singh, Abhishek; Du, Juan; Davis, Jonathan K.; Lee, Jung-Goo; Slabaugh, Erin; Vandavasi, Venu Gopal; O’Neill, Hugh; Roberts, Eric M.; Roberts, Alison W.; Yingling, Yaroslava G.; Haigler, Candace H.

2016-01-01

A six-lobed membrane spanning cellulose synthesis complex (CSC) containing multiple cellulose synthase (CESA) glycosyltransferases mediates cellulose microfibril formation. The number of CESAs in the CSC has been debated for decades in light of changing estimates of the diameter of the smallest microfibril formed from the β-1,4 glucan chains synthesized by one CSC. We obtained more direct evidence through generating improved transmission electron microscopy (TEM) images and image averages of the rosette-type CSC, revealing the frequent triangularity and average cross-sectional area in the plasma membrane of its individual lobes. Trimeric oligomers of two alternative CESA computational models corresponded well with individual lobe geometry. A six-fold assembly of the trimeric computational oligomer had the lowest potential energy per monomer and was consistent with rosette CSC morphology. Negative stain TEM and image averaging showed the triangularity of a recombinant CESA cytosolic domain, consistent with previous modeling of its trimeric nature from small angle scattering (SAXS) data. Six trimeric SAXS models nearly filled the space below an average FF-TEM image of the rosette CSC. In summary, the multifaceted data support a rosette CSC with 18 CESAs that mediates the synthesis of a fundamental microfibril composed of 18 glucan chains. PMID:27345599

Provision of Information to the Research Staff.

ERIC Educational Resources Information Center

Williams, Martha E.

The Information Sciences section at Illinois Institute of Technology Research Institute (IITRI) is now operating a Computer Search Center (CSC) for handling numerous machine-readable data bases. The computer programs are generalized in the sense that they will handle any incoming data base. This is accomplished by means of a preprocessor system…

Results of a Coordinated Specialty Care Program for Early Psychosis and Predictors of Outcomes.

PubMed

Nossel, Ilana; Wall, Melanie M; Scodes, Jennifer; Marino, Leslie A; Zilkha, Sacha; Bello, Iruma; Malinovsky, Igor; Lee, Rufina; Radigan, Marleen; Smith, Thomas E; Sederer, Lloyd; Gu, Gyojeong; Dixon, Lisa

2018-05-15

This study prospectively evaluated outcomes of OnTrackNY, a statewide coordinated specialty care (CSC) program for treatment of early psychosis in community settings, as well as predictors of outcomes. The sample included 325 individuals ages 16-30 with recent-onset nonaffective psychosis who were enrolled in OnTrackNY and who had at least one three-month follow-up. Clinicians provided data at baseline and quarterly up to one year. Domains assessed included demographic and clinical characteristics, social and occupational functioning, medications, suicidality and violence, hospitalization, and time to intervention. Primary outcomes included the symptoms, occupational functioning, and social functioning scales of the Global Assessment of Functioning (GAF), as adapted by the U.S. Department of Veterans Affairs Mental Illness Research, Education and Clinical Center; education and employment status; and psychiatric hospitalization rate. Education and employment rates increased from 40% to 80% by six months, hospitalization rates decreased from 70% to 10% by three months, and improvement in GAF scores continued for 12 months. Female gender, non-Hispanic white race-ethnicity, and more education at baseline predicted better education and employment status at follow-up. Individuals with early psychosis receiving CSC achieved significant improvements in education and employment and experienced a decrease in hospitalization rate. Demographic variables and baseline education predicted education and employment outcomes. CSC teams should make particular effort to support the occupational goals of individuals at increased risk of not engaging in work or school, including male participants and participants from racial and ethnic minority groups.

Effects of Comprehensive Stroke Care Capabilities on In-Hospital Mortality of Patients with Ischemic and Hemorrhagic Stroke: J-ASPECT Study

PubMed Central

Iihara, Koji; Nishimura, Kunihiro; Kada, Akiko; Nakagawara, Jyoji; Ogasawara, Kuniaki; Ono, Junichi; Shiokawa, Yoshiaki; Aruga, Toru; Miyachi, Shigeru; Nagata, Izumi; Toyoda, Kazunori; Matsuda, Shinya; Miyamoto, Yoshihiro; Suzuki, Akifumi; Ishikawa, Koichi B.; Kataoka, Hiroharu; Nakamura, Fumiaki; Kamitani, Satoru

2014-01-01

Background The effectiveness of comprehensive stroke center (CSC) capabilities on stroke mortality remains uncertain. We performed a nationwide study to examine whether CSC capabilities influenced in-hospital mortality of patients with ischemic and hemorrhagic stroke. Methods and Results Of the 1,369 certified training institutions in Japan, 749 hospitals responded to a questionnaire survey regarding CSC capabilities that queried the availability of personnel, diagnostic techniques, specific expertise, infrastructure, and educational components recommended for CSCs. Among the institutions that responded, data on patients hospitalized for stroke between April 1, 2010 and March 31, 2011 were obtained from the Japanese Diagnosis Procedure Combination database. In-hospital mortality was analyzed using hierarchical logistic regression analysis adjusted for age, sex, level of consciousness on admission, comorbidities, and the number of fulfilled CSC items in each component and in total. Data from 265 institutions and 53,170 emergency-hospitalized patients were analyzed. Mortality rates were 7.8% for patients with ischemic stroke, 16.8% for patients with intracerebral hemorrhage (ICH), and 28.1% for patients with subarachnoid hemorrhage (SAH). Mortality adjusted for age, sex, and level of consciousness was significantly correlated with personnel, infrastructural, educational, and total CSC scores in patients with ischemic stroke. Mortality was significantly correlated with diagnostic, educational, and total CSC scores in patients with ICH and with specific expertise, infrastructural, educational, and total CSC scores in patients with SAH. Conclusions CSC capabilities were associated with reduced in-hospital mortality rates, and relevant aspects of care were found to be dependent on stroke type. PMID:24828409

Effects of comprehensive stroke care capabilities on in-hospital mortality of patients with ischemic and hemorrhagic stroke: J-ASPECT study.

PubMed

Iihara, Koji; Nishimura, Kunihiro; Kada, Akiko; Nakagawara, Jyoji; Ogasawara, Kuniaki; Ono, Junichi; Shiokawa, Yoshiaki; Aruga, Toru; Miyachi, Shigeru; Nagata, Izumi; Toyoda, Kazunori; Matsuda, Shinya; Miyamoto, Yoshihiro; Suzuki, Akifumi; Ishikawa, Koichi B; Kataoka, Hiroharu; Nakamura, Fumiaki; Kamitani, Satoru

2014-01-01

The effectiveness of comprehensive stroke center (CSC) capabilities on stroke mortality remains uncertain. We performed a nationwide study to examine whether CSC capabilities influenced in-hospital mortality of patients with ischemic and hemorrhagic stroke. Of the 1,369 certified training institutions in Japan, 749 hospitals responded to a questionnaire survey regarding CSC capabilities that queried the availability of personnel, diagnostic techniques, specific expertise, infrastructure, and educational components recommended for CSCs. Among the institutions that responded, data on patients hospitalized for stroke between April 1, 2010 and March 31, 2011 were obtained from the Japanese Diagnosis Procedure Combination database. In-hospital mortality was analyzed using hierarchical logistic regression analysis adjusted for age, sex, level of consciousness on admission, comorbidities, and the number of fulfilled CSC items in each component and in total. Data from 265 institutions and 53,170 emergency-hospitalized patients were analyzed. Mortality rates were 7.8% for patients with ischemic stroke, 16.8% for patients with intracerebral hemorrhage (ICH), and 28.1% for patients with subarachnoid hemorrhage (SAH). Mortality adjusted for age, sex, and level of consciousness was significantly correlated with personnel, infrastructural, educational, and total CSC scores in patients with ischemic stroke. Mortality was significantly correlated with diagnostic, educational, and total CSC scores in patients with ICH and with specific expertise, infrastructural, educational, and total CSC scores in patients with SAH. CSC capabilities were associated with reduced in-hospital mortality rates, and relevant aspects of care were found to be dependent on stroke type.

Metabolomic mapping of cancer stem cells for reducing and exploiting tumor heterogeneity.

PubMed

Cuyàs, Elisabet; Verdura, Sara; Fernández-Arroyo, Salvador; Bosch-Barrera, Joaquim; Martin-Castillo, Begoña; Joven, Jorge; Menendez, Javier A

2017-11-21

Personalized cancer medicine based on the analysis of tumors en masse is limited by tumor heterogeneity, which has become a major obstacle to effective cancer treatment. Cancer stem cells (CSC) are emerging as key drivers of inter- and intratumoral heterogeneity. CSC have unique metabolic dependencies that are required not only for specific bioenergetic/biosynthetic demands but also for sustaining their operational epigenetic traits, i.e. self-renewal, tumor-initiation, and plasticity. Given that the metabolome is the final downstream product of all the -omic layers and, therefore, most representative of the biological phenotype, we here propose that a novel approach to better understand the complexity of tumor heterogeneity is by mapping and cataloging small numbers of CSC metabolomic phenotypes. The narrower metabolomic diversity of CSC states could be employed to reduce multidimensional tumor heterogeneity into dynamic models of fewer actionable sub-phenotypes. The identification of the driver nodes that are used differentially by CSC states to metabolically regulate self-renewal and tumor initation and escape chemotherapy might open new preventive and therapeutic avenues. The mapping of CSC metabolomic states could become a pioneering strategy to reduce the dimensionality of tumor heterogeneity and improve our ability to examine changes in tumor cell populations for cancer detection, prognosis, prediction/monitoring of therapy response, and detection of therapy resistance and recurrent disease. The identification of driver metabolites and metabolic nodes accounting for a large amount of variance within the CSC metabolomic sub-phenotypes might offer new unforeseen opportunities for reducing and exploiting tumor heterogeneity via metabolic targeting of CSC.

Serum erythropoietin levels in patients with central serous chorioretinopathy

PubMed Central

Turgut, Burak; Ilhan, Nevin; Uyar, Fatma Yayla; Celiker, Ulku; Demir, Tamer; Koca, Suleyman Serdar

2010-01-01

Objective To evaluate the levels of erythropoietin (EPO) in the serum in patients with central serous chorioretinopathy (CSC). Methods An institutional comperative clinical study. The serum EPO levels were measured with the enzyme-linked immunosorbent assay (ELISA) method, of 15 patients with active CSC (Group 1), 15 patients with inactive CSC (Group 2) and 15 healthy volunteers (Group 3). Kruskal–Wallis variance analysis and Mann–Whitney U test were used for statistical analysis. Results The patient and control groups were matched for age and sex. There was no statistically significant variation with regard to age and gender among the groups (P > 0.05). The mean serum EPO concentrations in patients with active CSC (Group 1), inactive CSC (Group 2) and in healthy controls (Group 3) were 11.39 ± 3.01 mlU/mL, 11.79 ± 3.78 mlU/mL and 11.95 ± 3.27 mlU/mL, respectively. There was no significant variation among the serum EPO concentrations of the study groups (P > 0.05). Conclusion These findings suggest no role of serum EPO in pathogenesis of CSC. PMID:28539767

Serum erythropoietin levels in patients with central serous chorioretinopathy.

PubMed

Turgut, Burak; Ilhan, Nevin; Uyar, Fatma Yayla; Celiker, Ulku; Demir, Tamer; Koca, Suleyman Serdar

2010-01-01

To evaluate the levels of erythropoietin (EPO) in the serum in patients with central serous chorioretinopathy (CSC). An institutional comperative clinical study. The serum EPO levels were measured with the enzyme-linked immunosorbent assay (ELISA) method, of 15 patients with active CSC (Group 1), 15 patients with inactive CSC (Group 2) and 15 healthy volunteers (Group 3). Kruskal-Wallis variance analysis and Mann-Whitney U test were used for statistical analysis. The patient and control groups were matched for age and sex. There was no statistically significant variation with regard to age and gender among the groups ( P > 0.05). The mean serum EPO concentrations in patients with active CSC (Group 1), inactive CSC (Group 2) and in healthy controls (Group 3) were 11.39 ± 3.01 mlU/mL, 11.79 ± 3.78 mlU/mL and 11.95 ± 3.27 mlU/mL, respectively. There was no significant variation among the serum EPO concentrations of the study groups ( P > 0.05). These findings suggest no role of serum EPO in pathogenesis of CSC.

The Critical, Clinical Role of Interferon-Beta in Regulating Cancer Stem Cell Properties in Triple-Negative Breast Cancer.

PubMed

Doherty, Mary R; Jackson, Mark W

2018-05-11

Triple-negative breast cancer (TNBC) the deadliest form of this disease currently lacks a targeted therapy and is characterized by increased risk of metastasis and presence of therapeutically resistant cancer stem cells (CSC). Recent evidence has demonstrated that the presence of an interferon (IFN)/signal transducer of activated transcription 1 (STAT1) gene signature correlates with improved therapeutic response and overall survival in TNBC patients. In agreement with these clinical observations, our recent work has demonstrated, in a cell model of TNBC that CSC have intrinsically repressed IFN signaling. Administration of IFN-β represses CSC properties, inducing a less aggressive non-CSC state. Moreover, an elevated IFN-β gene signature correlated with repressed CSC-related genes and an increased presence of tumor-infiltrating lymphocytes in TNBC specimens. We therefore propose that IFN-β be considered as a potential therapeutic option in the treatment of TNBC, to repress the CSC properties responsible for therapy failure. Future studies aim to improve methods to target delivery of IFN-β to tumors, to maximize therapeutic efficacy while minimizing systemic side effects.

Flow cytometric techniques for detection of candidate cancer stem cell subpopulations in canine tumour models.

PubMed

Blacking, T M; Waterfall, M; Samuel, K; Argyle, D J

2012-12-01

The cancer stem cell (CSC) hypothesis proposes that tumour growth is maintained by a distinct subpopulation of 'CSC'. This study applied flow cytometric methods, reported to detect CSC in both primary and cultured cancer cells of other species, to identify candidate canine subpopulations. Cell lines representing diverse canine malignancies, and cells derived from spontaneous canine tumours, were evaluated for expression of stem cell-associated surface markers (CD34, CD44, CD117 and CD133) and functional properties [Hoecsht 33342 efflux, aldehyde dehydrogenase (ALDH) activity]. No discrete marker-defined subsets were identified within established cell lines; cells derived directly from spontaneous tumours demonstrated more heterogeneity, although this diminished upon in vitro culture. Functional assays produced variable results, suggesting context-dependency. Flow cytometric methods may be adopted to identify putative canine CSC. Whilst cell lines are valuable in assay development, primary cells may provide a more rewarding model for studying tumour heterogeneity in the context of CSC. However, it will be essential to fully characterize any candidate subpopulations to ensure that they meet CSC criteria. © 2011 Blackwell Publishing Ltd.

Temporomandibular joint dysfunction after mandibular fracture in children: a 10-year review.

PubMed

Leuin, Shelby C; Frydendall, Emily; Gao, Dexiang; Chan, Kenny H

2011-01-01

To collect demographic and clinical data on pediatric mandibular fractures and to assess temporomandibular joint (TMJ) dysfunction in patients with condylar and subcondylar (C/SC) fractures. Retrospective case series of pediatric mandibular fractures (1999-2009) with follow-up telephone questionnaire of patients with C/SC fractures. Collected data included age, gender, unilateral vs bilateral C/SC fracture, presence of concomitant fracture, velocity of injury, and treatment modality. Tertiary care children's hospital. Of 164 patients with mandibular fractures, 83 (50.6%) had C/SC fractures, of which 45 (54.2%) completed the questionnaire. Helkimo Anamnestic Dysfunction Index (A(i)) quantification of TMJ dysfunction after C/SC fracture and treatment modality of C/SC fractures. Of the 164 patients, 122 (74.4%) were male (median age, 10.4 years; age range, 0.6-19.0 years). Of the 83 patients with C/SC fractures, 61 (73.5%) were male (median age, 9.1 years; age range, 1.1-18.7 years); 66 (79.5%) had unilateral fractures and 17 (20.5%) had bilateral fractures. The A(i) distribution of the 45 patients who completed the questionnaire was as follows: 15 (33.3%) none, 6 (13.3%) mild, and 24 (53.3%) severe. Females have more severe dysfunction than do males (95% confidence interval, 1.6-140.0; P = .02). No other significant predictors of treatment modality or TMJ dysfunction were identified. Patients with bilateral fracture are 8.1 times (95% confidence interval, 1.0-66.1 times; P = .05) more likely to have closed reduction than are those with unilateral fracture. This is one of the largest series of pediatric C/SC fractures reported in the recent literature. Findings are significant for increased severity of TMJ dysfunction in females and higher incidence of closed reduction in patients with bilateral C/SC fracture.

The Chandra Source Catalog: User Interface

NASA Astrophysics Data System (ADS)

Bonaventura, Nina; Evans, I. N.; Harbo, P. N.; Rots, A. H.; Tibbetts, M. S.; Van Stone, D. W.; Zografou, P.; Anderson, C. S.; Chen, J. C.; Davis, J. E.; Doe, S. M.; Evans, J. D.; Fabbiano, G.; Galle, E.; Gibbs, D. G.; Glotfelty, K. J.; Grier, J. D.; Hain, R.; Hall, D. M.; He, X.; Houck, J. C.; Karovska, M.; Lauer, J.; McCollough, M. L.; McDowell, J. C.; Miller, J. B.; Mitschang, A. W.; Morgan, D. L.; Nichols, J. S.; Nowak, M. A.; Plummer, D. A.; Primini, F. A.; Refsdal, B. L.; Siemiginowska, A. L.; Sundheim, B. A.; Winkelman, S. L.

2009-01-01

The Chandra Source Catalog (CSC) is the definitive catalog of all X-ray sources detected by Chandra. The CSC is presented to the user in two tables: the Master Chandra Source Table and the Table of Individual Source Observations. Each distinct X-ray source identified in the CSC is represented by a single master source entry and one or more individual source entries. If a source is unaffected by confusion and pile-up in multiple observations, the individual source observations are merged to produce a master source. In each table, a row represents a source, and each column a quantity that is officially part of the catalog. The CSC contains positions and multi-band fluxes for the sources, as well as derived spatial, spectral, and temporal source properties. The CSC also includes associated source region and full-field data products for each source, including images, photon event lists, light curves, and spectra. The master source properties represent the best estimates of the properties of a source, and are presented in the following categories: Position and Position Errors, Source Flags, Source Extent and Errors, Source Fluxes, Source Significance, Spectral Properties, and Source Variability. The CSC Data Access GUI provides direct access to the source properties and data products contained in the catalog. The user may query the catalog database via a web-style search or an SQL command-line query. Each query returns a table of source properties, along with the option to browse and download associated data products. The GUI is designed to run in a web browser with Java version 1.5 or higher, and may be accessed via a link on the CSC website homepage (http://cxc.harvard.edu/csc/). As an alternative to the GUI, the contents of the CSC may be accessed directly through a URL, using the command-line tool, cURL. Support: NASA contract NAS8-03060 (CXC).

Notch-1 induces Epithelial-mesenchymal transition consistent with cancer stem cell phenotype in pancreatic cancer cells

PubMed Central

Bao, Bin; Wang, Zhiwei; Ali, Shadan; Kong, Dejuan; Li, Yiwei; Ahmad, Aamir; Banerjee, Sanjeev; Azmi, Asfar S.; Miele, Lucio; Sarkar, Fazlul H.

2011-01-01

Activation of Notch-1 is known to be associated with the development and progression of human malignancies including pancreatic cancer. Emerging evidence suggest that the acquisition of epithelial-mesenchymal transition (EMT) phenotype and induction of cancer stem cell (CSC) or cancer stem-like cell phenotype are interrelated and contributes to tumor recurrence and drug resistance. The molecular mechanism(s) by which Notch-1 contributes to the acquisition of EMT phenotype and CSC self-renewal capacity has not been fully elucidated. Here we show that forced over-expression of Notch-1 leads to increased cell growth, clonogenicity, migration and invasion of AsPC-1 cells. Moreover, over-expression of Notch-1 led to the induction of EMT phenotype by activation of mesenchymal cell markers such as ZEB1, CD44, EpCAM, and Hes 1. Here we also report, for the first time, that over-expression of Notch-1 leads to increased expression of miR-21, and decreased expression of miR-200b, miR-200c, let-7a, let-7b, and let-7c. Re-expression of miR-200b led to decreased expression of ZEB1, and vimentin, and increased expression of E-cadherin. Over-expression of Notch-1 also increased the formation of pancreatospheres consistent with expression of CSC surface markers CD44 and EpCAM. Finally, we found that genistein, a known natural anti-tumor agent inhibited cell growth, clonogenicity, migration, invasion, EMT phenotype, formation of pancreatospheres and expression of CD44 and EpCAM. These results suggest that the activation of Notch-1 signaling contributes to the acquisition of EMT phenotype, which is in part mediated through the regulation of miR-200b and CSC self-renewal capacity, and these processes could be attenuated by genistein treatment. PMID:21463919

Fluorescent CSC models evidence that targeted nanomedicines improve treatment sensitivity of breast and colon cancer stem cells.

PubMed

Gener, Petra; Gouveia, Luis Pleno; Sabat, Guillem Romero; de Sousa Rafael, Diana Fernandes; Fort, Núria Bergadà; Arranja, Alexandra; Fernández, Yolanda; Prieto, Rafael Miñana; Ortega, Joan Sayos; Arango, Diego; Abasolo, Ibane; Videira, Mafalda; Schwartz, Simo

2015-11-01

To be able to study the efficacy of targeted nanomedicines in marginal population of highly aggressive cancer stem cells (CSC), we have developed a novel in vitro fluorescent CSC model that allows us to visualize these cells in heterogeneous population and to monitor CSC biological performance after therapy. In this model tdTomato reporter gene is driven by CSC specific (ALDH1A1) promoter and contrary to other similar models, CSC differentiation and un-differentiation processes are not restrained and longitudinal studies are feasible. We used this model for preclinical validation of poly[(d,l-lactide-co-glycolide)-co-PEG] (PLGA-co-PEG) micelles loaded with paclitaxel. Further, active targeting against CD44 and EGFR receptors was validated in breast and colon cancer cell lines. Accordingly, specific active targeting toward surface receptors enhances the performance of nanomedicines and sensitizes CSC to paclitaxel based chemotherapy. Many current cancer therapies fail because of the failure to target cancer stem cells. This surviving population soon proliferates and differentiates into more cancer cells. In this interesting article, the authors designed an in vitro cancer stem cell model to study the effects of active targeting using antibody-labeled micelles containing chemotherapeutic agent. This new model should allow future testing of various drug/carrier platforms before the clinical phase. Copyright © 2015 Elsevier Inc. All rights reserved.

The Chandra Source Catalog 2.0: Estimating Source Fluxes

NASA Astrophysics Data System (ADS)

Primini, Francis Anthony; Allen, Christopher E.; Miller, Joseph; Anderson, Craig S.; Budynkiewicz, Jamie A.; Burke, Douglas; Chen, Judy C.; Civano, Francesca Maria; D'Abrusco, Raffaele; Doe, Stephen M.; Evans, Ian N.; Evans, Janet D.; Fabbiano, Giuseppina; Gibbs, Danny G., II; Glotfelty, Kenny J.; Graessle, Dale E.; Grier, John D.; Hain, Roger; Hall, Diane M.; Harbo, Peter N.; Houck, John C.; Lauer, Jennifer L.; Laurino, Omar; Lee, Nicholas P.; Martínez-Galarza, Juan Rafael; McCollough, Michael L.; McDowell, Jonathan C.; McLaughlin, Warren; Morgan, Douglas L.; Mossman, Amy E.; Nguyen, Dan T.; Nichols, Joy S.; Nowak, Michael A.; Paxson, Charles; Plummer, David A.; Rots, Arnold H.; Siemiginowska, Aneta; Sundheim, Beth A.; Tibbetts, Michael; Van Stone, David W.; Zografou, Panagoula

2018-01-01

The Second Chandra Source Catalog (CSC2.0) will provide information on approximately 316,000 point or compact extended x-ray sources, derived from over 10,000 ACIS and HRC-I imaging observations available in the public archive at the end of 2014. As in the previous catalog release (CSC1.1), fluxes for these sources will be determined separately from source detection, using a Bayesian formalism that accounts for background, spatial resolution effects, and contamination from nearby sources. However, the CSC2.0 procedure differs from that used in CSC1.1 in three important aspects. First, for sources in crowded regions in which photometric apertures overlap, fluxes are determined jointly, using an extension of the CSC1.1 algorithm, as discussed in Primini & Kashyap (2014ApJ...796…24P). Second, an MCMC procedure is used to estimate marginalized posterior probability distributions for source fluxes. Finally, for sources observed in multiple observations, a Bayesian Blocks algorithm (Scargle, et al. 2013ApJ...764..167S) is used to group observations into blocks of constant source flux.In this poster we present details of the CSC2.0 photometry algorithms and illustrate their performance in actual CSC2.0 datasets.This work has been supported by NASA under contract NAS 8-03060 to the Smithsonian Astrophysical Observatory for operation of the Chandra X-ray Center.

Contrasting hypoxic effects on breast cancer stem cell hierarchy is dependent on ER-α status.

PubMed

Harrison, Hannah; Rogerson, Lynsey; Gregson, Hannah J; Brennan, Keith R; Clarke, Robert B; Landberg, Göran

2013-02-15

Tumor hypoxia is often linked to decreased survival in patients with breast cancer and current therapeutic strategies aim to target the hypoxic response. One way in which this is done is by blocking hypoxia-induced angiogenesis. Antiangiogenic therapies show some therapeutic potential with increased disease-free survival, but these initial promising results are short lived and followed by tumor progression. We hypothesized that this may be due to altered cancer stem cell (CSC) activity resulting from increased tumor hypoxia. We studied the effects of hypoxia on CSC activity, using in vitro mammosphere and holoclone assays as well as in vivo limiting dilution experiments, in 13 patient-derived samples and four cell lines. There was a HIF-1α-dependent CSC increase in ER-α-positive cancers following hypoxic exposure, which was blocked by inhibition of estrogen and Notch signaling. A contrasting decrease in CSC was seen in ER-α-negative cancers. We next developed a xenograft model of cell lines and patient-derived samples to assess the hypoxic CSC response. Varying sizes of xenografts were collected and analyzed for HIF1-α expression and CSC. The same ER-α-dependent contrasting hypoxic-CSC response was seen validating the initial observation. These data suggest that ER-α-positive and negative breast cancer subtypes respond differently to hypoxia and, as a consequence, antiangiogenic therapies will not be suitable for both subgroups.

Tissue Factor promotes breast cancer stem cell activity in vitro.

PubMed

Shaker, Hudhaifah; Harrison, Hannah; Clarke, Robert; Landberg, Goran; Bundred, Nigel J; Versteeg, Henri H; Kirwan, Cliona C

2017-04-18

Cancer stem cells (CSCs) are a subpopulation of cells that can self-renew and initiate tumours. The clotting-initiating protein Tissue Factor (TF) promotes metastasis and may be overexpressed in cancer cells with increased CSC activity. We sought to determine whether TF promotes breast CSC activity in vitro using human breast cancer cell lines. TF expression was compared in anoikis-resistant (CSC-enriched) and unselected cells. In cells sorted into of TF-expressing and TF-negative (FACS), and in cells transfected to knockdown TF (siRNA) and overexpress TF (cDNA), CSC activity was compared by (i) mammosphere forming efficiency (MFE) (ii) holoclone colony formation (Hc) and (iii) ALDH1 activity. TF expression was increased in anoikis-resistant and high ALDH1-activity T47D cells compared to unselected cells. FACS sorted TF-expressing T47Ds and TF-overexpressing MCF7s had increased CSC activity compared to TF-low cells. TF siRNA cells (MDAMB231,T47D) had reduced CSC activity compared to control cells. FVIIa increased MFE and ALDH1 in a dose-dependent manner (MDAMB231, T47D). The effects of FVIIa on MFE were abrogated by TF siRNA (T47D). Breast CSCs (in vitro) demonstrate increased activity when selected for high TF expression, when induced to overexpress TF, and when stimulated (with FVIIa). Targeting the TF pathway in vivo may abrogate CSC activity.

Inhibition of RAD51 by siRNA and Resveratrol Sensitizes Cancer Stem Cells Derived from HeLa Cell Cultures to Apoptosis

PubMed Central

Ruíz, Graciela; Valencia-González, Heriberto A.; León-Galicia, Ismael; García-Villa, Enrique

2018-01-01

Cervical cancer is the second most frequent tumor type in women worldwide with cases developing clinical recurrence, metastasis, and chemoresistance. The cancer stem cells (CSC) may be implicated in tumor resistance to therapy. RESveratrol (RES), a natural compound, is an antioxidant with multiple beneficial activities. We previously determined that the expression of RAD51 is decreased by RES. The aim of our study was to examine molecular mechanism by which CSC from HeLa cultures exhibit chemoresistance. We hypothesized CSC repair more efficiently DNA breaks and that RAD51 plays an important role in this mechanism. We found that CSC, derived from cervical cancer cell lines, overexpress RAD51 and are less sensitive to Etoposide (VP16). We inhibited RAD51 in CSC-enriched cultures using RES or siRNA against RAD51 messenger RNA and observed a decrease in cell viability and induction of apoptosis when treated simultaneously with VP16. In addition, we found that inhibition of RAD51 expression using RES also sensitizes CSC to VP16 treatment. Our results suggest that resveratrol is effective to sensitize cervical CSC because of RAD51 inhibition, targeting high RAD51 expressing CD49f-positive cells, which supports the possible therapeutic application of RES as a novel agent to treat cancer. PMID:29681946

41 CFR 101-28.306 - Customer supply center (CSC) accounts and related controls.

Code of Federal Regulations, 2010 CFR

2010-07-01

... PROCUREMENT 28-STORAGE AND DISTRIBUTION 28.3-Customer Supply Centers § 101-28.306 Customer supply center (CSC... 41 Public Contracts and Property Management 2 2010-07-01 2010-07-01 true Customer supply center (CSC) accounts and related controls. 101-28.306 Section 101-28.306 Public Contracts and Property...

Inhibition of the Autophagy Pathway Synergistically Potentiates the Cytotoxic Activity of Givinostat (ITF2357) on Human Glioblastoma Cancer Stem Cells.

PubMed

Angeletti, Francesca; Fossati, Gianluca; Pattarozzi, Alessandra; Würth, Roberto; Solari, Agnese; Daga, Antonio; Masiello, Irene; Barbieri, Federica; Florio, Tullio; Comincini, Sergio

2016-01-01

Increasing evidence highlighted the role of cancer stem cells (CSCs) in the development of tumor resistance to therapy, particularly in glioblastoma (GBM). Therefore, the development of new therapies, specifically directed against GBM CSCs, constitutes an important research avenue. Considering the extended range of cancer-related pathways modulated by histone acetylation/deacetylation processes, we studied the anti-proliferative and pro-apoptotic efficacy of givinostat (GVS), a pan-histone deacetylase inhibitor, on cell cultures enriched in CSCs, isolated from nine human GBMs. We report that GVS induced a significant reduction of viability and self-renewal ability in all GBM CSC cultures; conversely, GVS exposure did not cause a significant cytotoxic activity toward differentiated GBM cells and normal mesenchymal human stem cells. Analyzing the cellular and molecular mechanisms involved, we demonstrated that GVS affected CSC viability through the activation of programmed cell death pathways. In particular, a marked stimulation of macroautophagy was observed after GVS treatment. To understand the functional link between GVS treatment and autophagy activation, different genetic and pharmacological interfering strategies were used. We show that the up-regulation of the autophagy process, obtained by deprivation of growth factors, induced a reduction of CSC sensitivity to GVS, while the pharmacological inhibition of the autophagy pathway and the silencing of the key autophagy gene ATG7 , increased the cell death rate induced by GVS. Altogether these findings suggest that autophagy represents a pro-survival mechanism activated by GBM CSCs to counteract the efficacy of the anti-proliferative activity of GVS. In conclusion, we demonstrate that GVS is a novel pharmacological tool able to target GBM CSC viability and its efficacy can be enhanced by autophagy inhibitory strategies.

Designing single- and multiple-shell sampling schemes for diffusion MRI using spherical code.

PubMed

Cheng, Jian; Shen, Dinggang; Yap, Pew-Thian

2014-01-01

In diffusion MRI (dMRI), determining an appropriate sampling scheme is crucial for acquiring the maximal amount of information for data reconstruction and analysis using the minimal amount of time. For single-shell acquisition, uniform sampling without directional preference is usually favored. To achieve this, a commonly used approach is the Electrostatic Energy Minimization (EEM) method introduced in dMRI by Jones et al. However, the electrostatic energy formulation in EEM is not directly related to the goal of optimal sampling-scheme design, i.e., achieving large angular separation between sampling points. A mathematically more natural approach is to consider the Spherical Code (SC) formulation, which aims to achieve uniform sampling by maximizing the minimal angular difference between sampling points on the unit sphere. Although SC is well studied in the mathematical literature, its current formulation is limited to a single shell and is not applicable to multiple shells. Moreover, SC, or more precisely continuous SC (CSC), currently can only be applied on the continuous unit sphere and hence cannot be used in situations where one or several subsets of sampling points need to be determined from an existing sampling scheme. In this case, discrete SC (DSC) is required. In this paper, we propose novel DSC and CSC methods for designing uniform single-/multi-shell sampling schemes. The DSC and CSC formulations are solved respectively by Mixed Integer Linear Programming (MILP) and a gradient descent approach. A fast greedy incremental solution is also provided for both DSC and CSC. To our knowledge, this is the first work to use SC formulation for designing sampling schemes in dMRI. Experimental results indicate that our methods obtain larger angular separation and better rotational invariance than the generalized EEM (gEEM) method currently used in the Human Connectome Project (HCP).

EGF induces epithelial-mesenchymal transition and cancer stem-like cell properties in human oral cancer cells via promoting Warburg effect.

PubMed

Xu, Qilin; Zhang, Qunzhou; Ishida, Yasutaka; Hajjar, Souren; Tang, Xudong; Shi, Haoran; Dang, Chi V; Le, Anh D

2017-02-07

"Warburg effect", the enhanced glycolysis or aerobic glycolysis, confers cancer cells the ability to survive and proliferate even under stressed conditions. In this study, we explored the role of epidermal growth factor (EGF) in orchestrating Warburg effect, the epithelial-mesenchymal transition (EMT) process, and the acquisition of cancer stem-like cell properties in human oral squamous cell carcinoma (OSCC) cells. Our results showed that EGF induces EMT process in OSCC cells, which correlates with the acquisition of cancer stem-like properties, including the enrichment of CD44+/CD24- population of cancer cells and an increased expression of CSC-related genes, aldehyde dehydrogenase-1 (ALDH1) and Bmi-1. We also showed that EGF concomitantly enhanced L-lactate production, while blocking glycolysis by 2-deoxy-D-glucose (2-DG) robustly reversed EGF-induced EMT process and CSC-like properties in OSCC cells. Mechanistically, we demonstrated that EGF promoted EMT process and CSC generation through EGFR/PI3K/HIF-1α axis-orchestrated glycolysis. Using an orthotopic tumor model of human OSCC (UM-SCC1) injected in the tongue of BALB/c nude mice, we showed that treatment with 2-DG in vivo significantly inhibited the metastasis of tumor cells to the regional cervical lymph nodes and reduced the expression of ALDH1 and vimentin in both in situ tumors and tumor cell-invaded regional lymph nodes. Taken together, these findings have unveiled a new mechanism that EGF drives OSCC metastasis through induction of EMT process and CSC generation, which is driven by an enhanced glycolytic metabolic program in OSCC cells.

Inhibition of the Autophagy Pathway Synergistically Potentiates the Cytotoxic Activity of Givinostat (ITF2357) on Human Glioblastoma Cancer Stem Cells

PubMed Central

Angeletti, Francesca; Fossati, Gianluca; Pattarozzi, Alessandra; Würth, Roberto; Solari, Agnese; Daga, Antonio; Masiello, Irene; Barbieri, Federica; Florio, Tullio; Comincini, Sergio

2016-01-01

Increasing evidence highlighted the role of cancer stem cells (CSCs) in the development of tumor resistance to therapy, particularly in glioblastoma (GBM). Therefore, the development of new therapies, specifically directed against GBM CSCs, constitutes an important research avenue. Considering the extended range of cancer-related pathways modulated by histone acetylation/deacetylation processes, we studied the anti-proliferative and pro-apoptotic efficacy of givinostat (GVS), a pan-histone deacetylase inhibitor, on cell cultures enriched in CSCs, isolated from nine human GBMs. We report that GVS induced a significant reduction of viability and self-renewal ability in all GBM CSC cultures; conversely, GVS exposure did not cause a significant cytotoxic activity toward differentiated GBM cells and normal mesenchymal human stem cells. Analyzing the cellular and molecular mechanisms involved, we demonstrated that GVS affected CSC viability through the activation of programmed cell death pathways. In particular, a marked stimulation of macroautophagy was observed after GVS treatment. To understand the functional link between GVS treatment and autophagy activation, different genetic and pharmacological interfering strategies were used. We show that the up-regulation of the autophagy process, obtained by deprivation of growth factors, induced a reduction of CSC sensitivity to GVS, while the pharmacological inhibition of the autophagy pathway and the silencing of the key autophagy gene ATG7, increased the cell death rate induced by GVS. Altogether these findings suggest that autophagy represents a pro-survival mechanism activated by GBM CSCs to counteract the efficacy of the anti-proliferative activity of GVS. In conclusion, we demonstrate that GVS is a novel pharmacological tool able to target GBM CSC viability and its efficacy can be enhanced by autophagy inhibitory strategies. PMID:27833530

[The cultivation and identification of lacrimal gland adenoid cystic cancer stem cells].

PubMed

Lyu, Jianmei; He, Yanjin; Xie, Lianfeng; Liu, Xun; Zhu, Limin

2015-10-01

To isolate and cultivate the Lacrimal gland Adenoid Cystic Carcinoma cells line, study Cancer Stem Cells properties. Experimental study. Lacrimal gland adenoid cystic carcinoma cancer stem cells were cultivated in serum-free suspension culture and the morphological changes were observed. Cells were divided into two groups, the LACC-CSC experimental group and the LACC control group. The flow cytometry instrument was used to detect the expression of classical stem cell markers CD133 and ABCG2. Transwell chamber was used to detect the cancer stem cell aggressivity and differentiated into the vascular endothelial cells. The tumorigenic force in vitro xenotransplantation were applied. LACC cells can grow suspensively after vaccinated in serum free medium and form tumor microspheres after 10-12 days. Flow cytometry experiments showed that the expression ratio of stem cell markers CD133 in LACC-CSC was (35.67 ± 6.86)%, significantly different to LACC with (0.46 ± 0.48)%, (t = 8.867, P < 0.05). Similarly, the expression ratio of stem cell marker ABCG2 in LACC-CSC was (39.99 ± 4.54)%, significantly different to LACC with (6.75 ± 1.34)%, (t = -9.932, P < 0.05). In vitro experiment of Matrigel invasion, LACC-CSC went through the matrigel basement membrane averagely (32.60 ± 8.79)/HP contrary to LACC with average (10.20 ± 2.77)/HP after 24 hours, showing statistically significance (t = 5.433, P < 0.05) between the two groups. After training for 48 hours, the difference between two groups was still obvious (t = 5.779, P < 0.05) with LACC-CSC average (62.60 ± 4.83)/HP to LACC (44.00 ± 5.34)/HP. When induced by serum medium containing VEGF and bFGF, LACC-CSC grew adherent gradually and cell morphological changes occurred after continuous induction to long spindle cells. When cultured into three-dimensional matrix structure they formed vessel samples and expressed vascular endothelial marker CD31 and CD34. Transplanted tumor in vitro experiment, mice of LACC-CSC group grew tumors in 9 days with 100% tumorigenic rate, whereas LACC group 12 days with 100% tumorigenic rate. LACC-CSC can be obtained through serum-free culture method. LACC-CSC grew suspensively and expressed classical stem cell markers. LACC-CSC were identified as cancer stem cells with stronger migration and invasion. LACC-CSC have tumorigenic force and multi-directional differentiation potential with general characteristics of the stem cell.

Identification of a unique hepatocellular carcinoma line, Li-7, with CD13(+) cancer stem cells hierarchy and population change upon its differentiation during culture and effects of sorafenib.

PubMed

Yamada, Takeshi; Abei, Masato; Danjoh, Inaho; Shirota, Ryoko; Yamashita, Taro; Hyodo, Ichinosuke; Nakamura, Yukio

2015-04-11

Cancer stem cell (CSC) research has highlighted the necessity of developing drugs targeting CSCs. We investigated a hepatocellular carcinoma (HCC) cell line that not only has CSC hierarchy but also shows phenotypic changes (population changes) upon differentiation of CSC during culture and can be used for screening drugs targeting CSC. Based on a hypothesis that the CSC proportion should decrease upon its differentiation into progenitors (population change), we tested HCC cell lines (HuH-7, Li-7, PLC/PRF/5, HLF, HLE) before and after 2 months culture for several markers (CD13, EpCAM, CD133, CD44, CD90, CD24, CD166). Tumorigenicity was tested using nude mice. To evaluate the CSC hierarchy, we investigated reconstructivity, proliferation, ALDH activity, spheroid formation, chemosensitivity and microarray analysis of the cell populations sorted by FACS. Only Li-7 cells showed a population change during culture: the proportion of CD13 positive cells decreased, while that of CD166 positive cells increased. The high tumorigenicity of the Li-7 was lost after the population change. CD13(+)/CD166(-) cells showed slow growth and reconstructed the bulk Li-7 populations composed of CD13(+)/CD166(-), CD13(-)/CD166(-) and CD13(-)/CD166(+) fractions, whereas CD13(-)/CD166(+) cells showed rapid growth but could not reproduce any other population. CD13(+)/CD166(-) cells showed high ALDH activity, spheroid forming ability and resistance to 5-fluorouracil. Microarray analysis demonstrated higher expression of stemness-related genes in CD166(-) than CD166(+) fraction. These results indicated a hierarchy in Li-7 cells, in which CD13(+)/CD166(-) and CD13(-)/CD166(+) cells serve as slow growing CSCs and rapid growing progenitors, respectively. Sorafenib selectively targeted the CD166(-) fraction, including CD13(+) CSCs, which exhibited higher mRNA expression for FGF3 and FGF4, candidate biomarkers for sorafenib. 5-fluorouracil followed by sorafenib inhibited the growth of bulk Li-7 cells more effectively than the reverse sequence or either alone. We identified a unique HCC line, Li-7, which not only shows heterogeneity for a CD13(+) CSC hierarchy, but also undergoes a "population change" upon CSC differentiation. Sorafenib targeted the CSC in vitro, supporting the use of this model for screening drugs targeting the CSC. This type of "heterogeneous, unstable" cell line may prove more useful in the CSC era than conventional "homogeneous, stable" cell lines.

Microenvironment-Programmed Metastatic Prostate Cancer Stem Cells (mPCSCs)

DTIC Science & Technology

2015-10-01

osteoblastic differentiation during aging . Rejuvenation Res 2006;9:10–9. 25] Gao FB, Raff M. Cell size control and a cell-intrinsic maturation program in...self- renewing long-term tumor-propagating cells that resist castration. Cell Stem Cell 10, 556-569 (2012). 8. Rybak, A.P., Bristow, R.G., & Kapoor, A...established clinical tumor is sustained by subpopulations of self- renewing cancer cells operationally called cancer stem cells (CSC) that can generate

Chandra Source Catalog: User Interface

NASA Astrophysics Data System (ADS)

Bonaventura, Nina; Evans, Ian N.; Rots, Arnold H.; Tibbetts, Michael S.; van Stone, David W.; Zografou, Panagoula; Primini, Francis A.; Glotfelty, Kenny J.; Anderson, Craig S.; Chen, Judy C.; Davis, John E.; Doe, Stephen M.; Evans, Janet D.; Fabbiano, Giuseppina; Galle, Elizabeth C.; Gibbs, Danny G., II; Grier, John D.; Hain, Roger; Hall, Diane M.; Harbo, Peter N.; He, Helen; Houck, John C.; Karovska, Margarita; Kashyap, Vinay L.; Lauer, Jennifer; McCollough, Michael L.; McDowell, Jonathan C.; Miller, Joseph B.; Mitschang, Arik W.; Morgan, Douglas L.; Mossman, Amy E.; Nichols, Joy S.; Nowak, Michael A.; Plummer, David A.; Refsdal, Brian L.; Siemiginowska, Aneta L.; Sundheim, Beth A.; Winkelman, Sherry L.

2009-09-01

The Chandra Source Catalog (CSC) is intended to be the definitive catalog of all X-ray sources detected by Chandra. For each source, the CSC provides positions and multi-band fluxes, as well as derived spatial, spectral, and temporal source properties. Full-field and source region data products are also available, including images, photon event lists, light curves, and spectra. The Chandra X-ray Center CSC website (http://cxc.harvard.edu/csc/) is the place to visit for high-level descriptions of each source property and data product included in the catalog, along with other useful information, such as step-by-step catalog tutorials, answers to FAQs, and a thorough summary of the catalog statistical characterization. Eight categories of detailed catalog documents may be accessed from the navigation bar on most of the 50+ CSC pages; these categories are: About the Catalog, Creating the Catalog, Using the Catalog, Catalog Columns, Column Descriptions, Documents, Conferences, and Useful Links. There are also prominent links to CSCview, the CSC data access GUI, and related help documentation, as well as a tutorial for using the new CSC/Google Earth interface. Catalog source properties are presented in seven scientific categories, within two table views: the Master Source and Source Observations tables. Each X-ray source has one ``master source'' entry and one or more ``source observation'' entries, the details of which are documented on the CSC ``Catalog Columns'' pages. The master source properties represent the best estimates of the properties of a source; these are extensively described on the following pages of the website: Position and Position Errors, Source Flags, Source Extent and Errors, Source Fluxes, Source Significance, Spectral Properties, and Source Variability. The eight tutorials (``threads'') available on the website serve as a collective guide for accessing, understanding, and manipulating the source properties and data products provided by the catalog.

Investigation of MACC1 Gene Expression in Head and Neck Cancer and Cancer Stem Cells.

PubMed

Evran, Ebru; Şahin, Hilal; Akbaş, Kübra; Çiğdem, Sadik; Gündüz, Esra

2016-12-01

By investigating the MACC1 gene (metastasis-associated in colon cancer 1) in cancer stem cells (CSC) resistant to chemotherapy and in cancer stem cells (CSC) resistant to chemotherapy and in cancer cells (CS) sensitive to chemotherapy we determineda steady expression in both types of cells in head and neck cancer. In conformity with the result we examined if this gene could be a competitor gene for chemotherapy. According to literature, the MACC1 gene shows a clear expression in head and neck cancer cells [1]. Here we examined MACC1 expression in CSC and investigated it as a possible biomarker. Our experiments were performed in the UT -SCC -74 in primary head and neck cancer cell line. We examined the MACC -1 gene expression by Real Time PCR from both isolated CSC and CS. Expression of MACC -1 gene of cancer stem cells showed an two-fold increase compared with cancer cells. Based on the positive expression of MACC1 in both CS and CSC, this gene may serve as a potential biomarker in head and neck cancer. By comparing the results of this study with the novel features of MACC1, two important hypotheses could be examined. The first hypothesis is that MACC1 is a possible transcripton factor in colon cancer, which influences a high expression of CSC in head and neck and affects the expression of three biomarkers of the CSC control group biomarkers. The second hypothesisis is that the positive expression of MACC1 in patients with a malignant prognosis of tongue cancer, which belongs to head and neck cancer types, operates a faster development of CSC to cancer cells.

Targeting cancer stem cell-specific markers and/or associated signaling pathways for overcoming cancer drug resistance.

PubMed

Ranji, Peyman; Salmani Kesejini, Tayyebali; Saeedikhoo, Sara; Alizadeh, Ali Mohammad

2016-10-01

Cancer stem cells (CSCs) are a small subpopulation of tumor cells with capabilities of self-renewal, dedifferentiation, tumorigenicity, and inherent chemo-and-radio therapy resistance. Tumor resistance is believed to be caused by CSCs that are intrinsically challenging to common treatments. A number of CSC markers including CD44, CD133, receptor tyrosine kinase, aldehyde dehydrogenases, epithelial cell adhesion molecule/epithelial specific antigen, and ATP-binding cassette subfamily G member 2 have been proved as the useful targets for defining CSC population in solid tumors. Furthermore, targeting CSC markers through new therapeutic strategies will ultimately improve treatments and overcome cancer drug resistance. Therefore, the identification of novel strategies to increase sensitivity of CSC markers has major clinical implications. This review will focus on the innovative treatment methods such as nano-, immuno-, gene-, and chemotherapy approaches for targeting CSC-specific markers and/or their associated signaling pathways.

Predicting adsorptive removal of chlorophenol from aqueous solution using artificial intelligence based modeling approaches.

PubMed

Singh, Kunwar P; Gupta, Shikha; Ojha, Priyanka; Rai, Premanjali

2013-04-01

The research aims to develop artificial intelligence (AI)-based model to predict the adsorptive removal of 2-chlorophenol (CP) in aqueous solution by coconut shell carbon (CSC) using four operational variables (pH of solution, adsorbate concentration, temperature, and contact time), and to investigate their effects on the adsorption process. Accordingly, based on a factorial design, 640 batch experiments were conducted. Nonlinearities in experimental data were checked using Brock-Dechert-Scheimkman (BDS) statistics. Five nonlinear models were constructed to predict the adsorptive removal of CP in aqueous solution by CSC using four variables as input. Performances of the constructed models were evaluated and compared using statistical criteria. BDS statistics revealed strong nonlinearity in experimental data. Performance of all the models constructed here was satisfactory. Radial basis function network (RBFN) and multilayer perceptron network (MLPN) models performed better than generalized regression neural network, support vector machines, and gene expression programming models. Sensitivity analysis revealed that the contact time had highest effect on adsorption followed by the solution pH, temperature, and CP concentration. The study concluded that all the models constructed here were capable of capturing the nonlinearity in data. A better generalization and predictive performance of RBFN and MLPN models suggested that these can be used to predict the adsorption of CP in aqueous solution using CSC.

Interim Report on the AAC-Mellon Project from Knox College.

ERIC Educational Resources Information Center

Peterson, James; Bailey, Stephen

In 1985, Knox College was chosen to participate in the Association of American Colleges/Mellon Transfer Grant Program, which sought to assist community college students in making the transition to the four-year college environment. Four local community colleges, Carl Sandburg College (CSC), Illinois Central College (ICC), Blackhawk East Community…

7 CFR 1776.16 - Loan servicing.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 7 Agriculture 12 2014-01-01 2013-01-01 true Loan servicing. 1776.16 Section 1776.16 Agriculture... (CONTINUED) HOUSEHOLD WATER WELL SYSTEM GRANT PROGRAM HWWS Loans § 1776.16 Loan servicing. (a) If RUS... administrative expense as provided in § 1776.13. (b) If RUS determines that CSC is not able to service HWWS loans...

7 CFR 1776.16 - Loan servicing.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 12 2010-01-01 2010-01-01 false Loan servicing. 1776.16 Section 1776.16 Agriculture... (CONTINUED) HOUSEHOLD WATER WELL SYSTEM GRANT PROGRAM HWWS Loans § 1776.16 Loan servicing. (a) If RUS... administrative expense as provided in § 1776.13. (b) If RUS determines that CSC is not able to service HWWS loans...

7 CFR 1776.16 - Loan servicing.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 12 2011-01-01 2011-01-01 false Loan servicing. 1776.16 Section 1776.16 Agriculture... (CONTINUED) HOUSEHOLD WATER WELL SYSTEM GRANT PROGRAM HWWS Loans § 1776.16 Loan servicing. (a) If RUS... administrative expense as provided in § 1776.13. (b) If RUS determines that CSC is not able to service HWWS loans...

7 CFR 1776.16 - Loan servicing.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 7 Agriculture 12 2012-01-01 2012-01-01 false Loan servicing. 1776.16 Section 1776.16 Agriculture... (CONTINUED) HOUSEHOLD WATER WELL SYSTEM GRANT PROGRAM HWWS Loans § 1776.16 Loan servicing. (a) If RUS... administrative expense as provided in § 1776.13. (b) If RUS determines that CSC is not able to service HWWS loans...

7 CFR 1776.16 - Loan servicing.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 7 Agriculture 12 2013-01-01 2013-01-01 false Loan servicing. 1776.16 Section 1776.16 Agriculture... (CONTINUED) HOUSEHOLD WATER WELL SYSTEM GRANT PROGRAM HWWS Loans § 1776.16 Loan servicing. (a) If RUS... administrative expense as provided in § 1776.13. (b) If RUS determines that CSC is not able to service HWWS loans...

[Wood smoke condensate had weak proliferation and strong necrotic effects on human airway smooth muscle cells].

PubMed

Pan, Yi-ling; Li, Bing; Ran, Pi-xin

2013-08-01

To investigate the effect of wood smoke condensate (WSC) on proliferation and necrosis of human airway smooth muscle cells (HASMCs). Primary cultured HASMCs between passage 2 and 8 were divided into 3 groups: a control group, a WSC group and a cigarette smoke condensate (CSC) group. The viability of cells was examined by the CCK8 assays. The ratio of cellular proliferative stage (S phase) and cell cycle index were examined by fluorescent-labeled thymidine analogue uptake assays and flow cytometry. The expression of cyclin D1 was detected by quantitative reverse transcriptase polymerase chain reaction (Q-PCR) and Western blot. Cell apoptosis and necrosis were observed by the annexin-V and PI staining. Statistical analysis was performed by using the One-way ANOVA and LSD-t test. Cell viability reached peak at WSC 1 mg/L[(126 ± 12)%] and at CSC 10 mg/L exposure level [(142 ± 11) %] respectively. While at WSC 10 mg/L and CSC 60 mg/L exposure levels, cell viability decreased significantly to 86% and 76%, respectively, as compared with that of the blank control group[(100 ± 0)%] (q = 3.63- 9.33, P < 0.05). In the WSC 1 mg/L group, the cell proliferation ratio and the expression of cyclin D1 protein were (124 ± 20)% and 1.31 ± 0.64, respectively, the differences being significant as compared with the blank control group [(100 ± 0)%, 1.0 ± 0.0] (q = 5.85, 5.91, P < 0.05), while the expression of cyclin D1 mRNA and the percentage of S+G2M phase were 1.18 ± 0.21 and (103 ± 4)%, respectively, not significantly different as compared to the control group [(100 ± 0)%, 1.0 ± 0.0], (q = 1.16, 2.05, P > 0.05). In the CSC 10 mg/L group, the above-mentioned values were (204 ± 45)%, 1.80 ± 0.25, (140 ± 6)%, 1.48 ± 0.2, respectively, which were significantly higher than those in the blank control group (q = 5.38-16.51, P < 0.05) and in the WSC group (q = 3.33-15.35, P < 0.05). However, when HASMCs were exposed to WSC 10 mg/L, the cell death ratio was (13.39 ± 0.15)%, higher than that of the blank control group [(1.57 ± 0.41)%] and the CSC group [(6.61 ± 1.91)%] (q = 18.03, 10.34, P < 0.05). Apoptosis ratio in the CSC 40 mg/L group was [(61.8 ± 10.6)%], higher than that of the blank control group [(0.0 ± 0.0)%] and the WSC group [(1.7 ± 0.4)%] (q = 17.44, 16.95, P < 0.05). Exposure to WSC caused a weak proliferation of HASMCs, but resulted in cell necrosis instead of apoptosis at high doses. There was a slight difference in cell effects between the WSC group and the CSC group.

Cancer Stem Cells and Chemoresistance: The Smartest Survives the Raid

PubMed Central

Zhao, Jihe

2016-01-01

Chemoresistant metastatic relapse of minimal residual disease plays a significant role for poor prognosis of cancer. Growing evidence supports a critical role of cancer stem cell (CSC) behind the mechanisms for this deadly disease. This review briefly introduces the basics of the conventional chemotherapies, updates the CSC theories, highlights the molecular and cellular mechanisms by which CSC smartly designs and utilizes multiple lines of self-defense to avoid being killed by chemotherapy, and concisely summarizes recent progress in studies on CSC-targeted therapies in the end, with the hope to help guide future research towards developing more effective therapeutic strategies to eradicate tumor cells in the patients. PMID:26899500

The acceptance of the collagen sponge diaphragm as an intravaginal contraceptive in human volunteers.

PubMed

Chvapil, M; Heine, M W; Horton, H

1976-12-01

Two types of highly resilient and liquid-absorbent collagen sponge contraceptives (CSC) in the shape of cylindrical cups (6 cm wide and 2.5 cm thick) were evaluated for acceptance as an intravaginal contraceptive method for a period of 3 months in 27 volunteers. Parameters such as retention, odor, irritation, itching, discharge, and convenience for the user and her sexual partner were tested. Average retention time was 7 to 9 days (range, 2 to 28 days); still, most sexually active volunteers preferred to remove the CSC every 3 to 4 days, rinse them in tap water, and reinsert them. Odor was noticed by users in 4% of the tested sponges and in 30% of all volunteers by medical personnel at the time of removal of the CSC from the vagina. No irritation, itching, or discharge was reported. The CSC alone did not cause any inconvenience to the user or partner, while the CSC with inserted rubber ring was felt by both partners and was found to be dislocated. This study indicates good acceptance of the CSC in intravaginal use. Studies to evaluate the efficacy of collagen sponges as mechanical contraceptive barriers are in progress.

The Northeast Climate Science Center

NASA Astrophysics Data System (ADS)

Ratnaswamy, M. J.; Palmer, R. N.; Morelli, T.; Staudinger, M.; Holland, A. R.

2013-12-01

The Department of Interior Northeast Climate Science Center (NE CSC) is part of a federal network of eight Climate Science Centers created to provide scientific information, tools, and techniques that managers and other parties interested in land, water, wildlife and cultural resources can use to anticipate, monitor, and adapt to climate change. Recognizing the critical threats, unique climate challenges, and expansive and diverse nature of the northeast region, the University of Massachusetts Amherst, College of Menominee Nation, Columbia University, Marine Biological Laboratory, University of Minnesota, University of Missouri Columbia, and University of Wisconsin-Madison have formed a consortium to host the NE CSC. This partnership with the U.S. Geological Survey climate science center network provides wide-reaching expertise, resources, and established professional collaborations in both climate science and natural and cultural resources management. This interdisciplinary approach is needed for successfully meeting the regional needs for climate impact assessment, adaptive management, education, and stakeholder outreach throughout the northeast region. Thus, the NE CSC conducts research, both through its general funds and its annual competitive award process, that responds to the needs of natural resource management partners that exist, in part or whole, within the NE CSC bounds. This domain includes the North Atlantic, Upper Midwest and Great Lakes, Eastern Tallgrass and Big Rivers, and Appalachian Landscape Conservation Cooperatives (LCCs), among other management stakeholders. For example, researchers are developing techniques to monitor tree range dynamics as affected by natural disturbances which can enable adaptation of projected climate impacts; conducting a Designing Sustainable Landscapes project to assess the capability of current and potential future landscapes in the Northeast to provide integral ecosystems and suitable habitat for a suite of representative species and provide guidance for strategic habitat conservation; studying the effects of changes in the frequency and magnitude of drought and stream temperature on brook trout habitats, spatial distribution and population persistence; and conducting assessments of northeastern regional climate projections and high-resolution downscaling.

Momentary symptoms of Borderline Personality Disorder as a product of trait personality and social context

PubMed Central

Hepp, Johanna; Carpenter, Ryan W.; Lane, Sean P.

2016-01-01

Past studies identify Five Factor Model (FFM) domains that are characteristic of Borderline Personality Disorder (BPD), including those associated with specific BPD symptoms, at a between-person level. The present study replicated these between-person associations and extended past research by assessing whether the FFM explains within-person variance in the manifestation of momentary BPD symptoms in the presence or absence of close social contact (CSC). We measured CSC and the BPD core symptoms negative affectivity, impulsivity, and interpersonal problems in 74 BPD patients and in a clinical control group of 40 depressed patients over the course of 28 days, six times a day. The FFM domains showed specificity in predicting momentary BPD symptoms and interacted with CSC in doing so. In particular, for BPD individuals only, momentary impulsivity and interpersonal problems were associated with higher Neuroticism and Extraversion and lower Agreeableness, and these associations were especially strong in situations involving CSC. Negative affectivity was predicted by Neuroticism for both groups of individuals, and this association was generally unaffected by CSC. Overall, experiencing CSC was positively associated with momentary BPD symptoms. Thus, both the FFM and CSC were associated with BPD patients’ experience of symptoms in everyday life. Furthermore, specific FFM trait domains were particularly impactful in contexts where BPD symptoms are more likely to be manifested, providing further evidence that person-by-situation interactions are important for understanding BPD symptoms in the moment. PMID:26901455

Effectiveness of collaborative stepped care for anxiety disorders in primary care: a pragmatic cluster randomised controlled trial.

PubMed

Muntingh, Anna; van der Feltz-Cornelis, Christina; van Marwijk, Harm; Spinhoven, Philip; Assendelft, Willem; de Waal, Margot; Adèr, Herman; van Balkom, Anton

2014-01-01

Collaborative stepped care (CSC) may be an appropriate model to provide evidence-based treatment for anxiety disorders in primary care. In a cluster randomised controlled trial, the effectiveness of CSC compared to care as usual (CAU) for adults with panic disorder (PD) or generalised anxiety disorder (GAD) in primary care was evaluated. Thirty-one psychiatric nurses who provided their services to 43 primary care practices in the Netherlands were randomised to deliver CSC (16 psychiatric nurses, 23 practices) or CAU (15 psychiatric nurses, 20 practices). CSC was provided by the psychiatric nurses (care managers) in collaboration with the general practitioner and a consultant psychiatrist. The intervention consisted of 3 steps, namely guided self-help, cognitive behavioural therapy and antidepressants. Anxiety symptoms were measured with the Beck Anxiety Inventory (BAI) at baseline and after 3, 6, 9 and 12 months. We recruited 180 patients with a DSM-IV diagnosis of PD or GAD, of whom 114 received CSC and 66 received usual primary care. On the BAI, CSC was superior to CAU [difference in gain scores from baseline to 3 months: -5.11, 95% confidence interval (CI) -8.28 to -1.94; 6 months: -4.65, 95% CI -7.93 to -1.38; 9 months: -5.67, 95% CI -8.97 to -2.36; 12 months: -6.84, 95% CI -10.13 to -3.55]. CSC, with guided self-help as a first step, was more effective than CAU for primary care patients with PD or GAD.

IQGAP1 Is Involved in Enhanced Aggressive Behavior of Epithelial Ovarian Cancer Stem Cell-Like Cells During Differentiation.

PubMed

Huang, Lu; Xu, Shanshan; Hu, Dongxiao; Lu, Weiguo; Xie, Xing; Cheng, Xiaodong

2015-05-01

Wide metastasis is one of characteristics of ovarian cancer. Cancer stem cells, as a source in cancer invasion and metastasis, possess powerful potential of differentiation. Scaffolding IQ domain GTPase-activating protein 1 (IQGAP1) plays a key role in the invasion and metastasis of cancer cells, but IQGAP1's role in cancer stem cells including ovarian cancer was unclear. Spheroid culture with serum-free medium was used for enriching ovarian cancer stem cell-like cells (CSC-LCs) from 3AO cell line, and a medium with 10% fetal bovine serum was used to induce the differentiation of CSC-LCs. Immunofluorescence was for detecting the stem markers OCT4 and SOX2. The quantitative real-time-polymerase chain reaction and Western blotting were performed to determine the messenger RNA and protein expression of IQGAP1, respectively. The capacity of cell invasion was evaluated by transwell chamber assay. Ovarian CSC-LCs obtained through spheroid culture showed irregularly elongated appearance, CD24 negative, and OCT4 and SOX2 positive. IQGAP1 expression was decreased in ovarian CSC-LCs compared with parental 3AO cells, but increased de novo during the differentiation of CSC-LCs. Knockdown of IQGAP1 by specific small interfering RNA remarkably weakened invasion capacity of 2-day differentiated ovarian CSC-LCs. Increased IQGAP1 expression during the differentiation of CSC-LCs is involved in an aggressive cell behavior, which may contribute to metastasis of ovarian cancer.

Biometric characteristics of eyes with central serous chorioretinopathy.

PubMed

Oh, Jong-Hyun; Oh, Jaeryung; Togloom, Ariunaa; Kim, Seong-Woo; Huh, Kuhl

2014-03-13

To investigate the biometric characteristics of eyes with idiopathic central serous chorioretinopathy (CSC). Medical records of 52 consecutive patients with unilateral CSC were reviewed. Central serous chorioretinopathy was diagnosed using spectral-domain optical coherence tomography (SD-OCT) and fluorescein angiography. Data collected for comparison with fellow eyes were refractive error, biometric measurements using partial coherence interferometry, and SD-OCT parameters. Mean time from subjective symptom onset to initial visit was 8.3 ± 12.29 weeks. Mean axial length (AL) was shorter in CSC eyes than in fellow eyes by 0.24 ± 0.379 mm (P < 0.001), and mean anterior chamber depth (ACD) was shallower in CSC eyes than in fellow eyes by 0.03 ± 0.088 mm (P = 0.021). Central serous chorioretinopathy eyes also had thicker subfoveal choroidal thickness (CT) than fellow eyes by 34.0 ± 45.93 μm (P < 0.001). Differences in spherical equivalents between CSC and fellow eyes correlated with AL differences (r = -0.690, P < 0.001) and CT differences (r = 0.473, P = 0.001). On multiple linear regression analysis, the differences in ACD between CSC and fellow eyes were significantly correlated with AL differences (P = 0.032) and symptom duration (P = 0.019). Biometric characteristics such as AL and ACD were different between eyes with CSC and fellow eyes. Variations in biometry, which correlated with CT differences, might be related to differences in refractive errors between eyes.

Cigarette smoke-induced DNA damage and repair detected by the comet assay in HPV-transformed cervical cells.

PubMed

Moktar, Afsoon; Ravoori, Srivani; Vadhanam, Manicka V; Gairola, C Gary; Gupta, Ramesh C

2009-12-01

Human papillomavirus (HPV) is the causative factor in the development and progression of cervical cancers in >97% of the cases, although insufficient. Epidemiological studies suggest an elevated risk of cervical cancer for cigarette smokers; therefore, we examined cigarette smoke-induced DNA damage and repair in HPV16-transformed human ectocervical cells (ECT1/E6 E7). Cells were treated with cigarette smoke condensate (CSC) for 72 h to assess the formation of single- and double-strand DNA breaks, measured by alkaline and neutral single cell gel electrophoresis assays, respectively. The mean tail length of cells with single-strand breaks was increased by 1.8-, 2.7- and 3.7-fold (p<0.001) after treatment with 4, 8 and 12 microg/ml CSC, respectively. The tail length with double-strand breaks was also increased dose-dependently. These results were further supported by measurement of the mean tail moment: the increase in both single- and double-strand breaks were much more pronounced with increasing concentration of CSC, by up to 23.5-fold (p<0.0001 for both assays). To examine the DNA repair, cells were treated with CSC for 72 h, followed by CSC withdrawal and re-incubation of the cells with fresh medium for 24, 48, or 72 h. Both single- and double-strand DNA breaks were removed during the initial 24 h but no further removal of the damage was observed. Up to 80% of residual single- and double-strand DNA breaks (p<0.05) were found to persist at all CSC concentrations examined. Ellagic acid, a known antioxidant and free-radical scavenger, was found to significantly inhibit DNA breaks induced by CSC. Thus, free radicals may be a plausible source of CSC-induced DNA damage. These data show that CSC-mediated DNA strand breaks are highly persistent, and suggest that persistence of cigarette smoke-associated DNA damage in the presence of HPV infection may lead to increased mutations in cervical cells and ultimately higher cancer risk.

Coronal Heating Topology: The Interplay of Current Sheets and Magnetic Field Lines

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

Rappazzo, A. F.; Velli, M.; Matthaeus, W. H.

2017-07-20

The magnetic topology and field line random walk (FLRW) properties of a nanoflare-heated and magnetically confined corona are investigated in the reduced magnetohydrodynamic regime. Field lines originating from current sheets form coherent structures, called current sheet connected (CSC) regions, which extend around them. CSC FLRW is strongly anisotropic, with preferential diffusion along the current sheets’ in-plane length. CSC FLRW properties remain similar to those of the entire ensemble but exhibit enhanced mean square displacements and separations due to the stronger magnetic field intensities in CSC regions. The implications for particle acceleration and heat transport in the solar corona and wind,more » and for solar moss formation are discussed.« less

Military, University, and Police Agency Command and Staff Colleges in the United States

ERIC Educational Resources Information Center

Martin, Richard H.

2017-01-01

This article discusses three models of command and staff colleges (CSC). Five university models, five United States Military models, and one police agency model are discussed. The 11 CSCs provide leadership development in various training and education programs all leading to the increased capabilities of leaders and potential leaders for public…

39 CFR 3050.22 - Documentation supporting attributable cost estimates in the Postal Service's section 3652 report.

Code of Federal Regulations, 2014 CFR

2014-07-01

... the updated factors and input data sets from the supporting data systems used, including: (1) The In... Determination. (b) The CRA report, including relevant data on international mail services; (c) The Cost Segments and Components (CSC) report; (d) All input data and processing programs used to produce the CRA report...

39 CFR 3050.22 - Documentation supporting attributable cost estimates in the Postal Service's section 3652 report.

Code of Federal Regulations, 2011 CFR

2011-07-01

... the updated factors and input data sets from the supporting data systems used, including: (1) The In... Determination. (b) The CRA report, including relevant data on international mail services; (c) The Cost Segments and Components (CSC) report; (d) All input data and processing programs used to produce the CRA report...

39 CFR 3050.22 - Documentation supporting attributable cost estimates in the Postal Service's section 3652 report.

Code of Federal Regulations, 2013 CFR

2013-07-01

... the updated factors and input data sets from the supporting data systems used, including: (1) The In... Determination. (b) The CRA report, including relevant data on international mail services; (c) The Cost Segments and Components (CSC) report; (d) All input data and processing programs used to produce the CRA report...

39 CFR 3050.22 - Documentation supporting attributable cost estimates in the Postal Service's section 3652 report.

Code of Federal Regulations, 2012 CFR

2012-07-01

... the updated factors and input data sets from the supporting data systems used, including: (1) The In... Determination. (b) The CRA report, including relevant data on international mail services; (c) The Cost Segments and Components (CSC) report; (d) All input data and processing programs used to produce the CRA report...

Mitostemness.

PubMed

Cuyàs, Elisabet; Verdura, Sara; Folguera-Blasco, Núria; Bastidas-Velez, Cristian; Martin, Ángel G; Alarcón, Tomás; Menendez, Javier A

2018-06-09

Unraveling the key mechanisms governing the retention versus loss of the cancer stem cell (CSC) state would open new therapeutic avenues to eradicate cancer. Mitochondria are increasingly recognized key drivers in the origin and development of CSC functional traits. We here propose the new term "mitostemness" to designate the mitochondria-dependent signaling functions that, evolutionary rooted in the bacterial origin of mitochondria, regulate the maintenance of CSC self-renewal and resistance to differentiation. Mitostemness traits, namely mitonuclear communication, mitoproteome components, and mitochondrial fission/fusion dynamics, can be therapeutically exploited to target the CSC state. We briefly review the pre-clinical evidence of action of investigational compounds on mitostemness traits and discuss ongoing strategies to accelerate the clinical translation of new mitostemness drugs. The recognition that the bacterial origin of present-day mitochondria can drive decision-making signaling phenomena may open up a new therapeutic dimension against life-threating CSCs. New therapeutics aimed to target mitochondria not only as biochemical but also as biophysical and morpho-physiological hallmarks of CSC might certainly guide improvements to cancer treatment.

Modeling the Effect of Cigarette Smoke on Hexose Utilization in Spermatocytes

PubMed Central

Esakky, Prabagaran; Debosch, Brian J.; Schoeller, Erica L.; Chi, Maggie M.; Moley, Kelle H.

2015-01-01

We set out to determine whether the addition of an aryl hydrocarbon receptor (AHR) antagonist has an effect on glucose/fructose utilization in the spermatocyte when exposed to cigarette smoke condensate (CSC). We exposed male germ cells to 5 and 40 μg/mL of CSC ± 10 μmol/L of AHR antagonist at various time points. Immunoblot expression of specific glucose/fructose transporters was compared to control. Radiolabeled uptake of 2-deoxyglucose (2-DG) and fructose was also performed. Spermatocytes utilized fructose nearly 50-fold more than 2-DG. Uptake of 2-DG decreased after CSC + AHR antagonist exposure. Glucose transporters (GLUTs) 9a and 12 declined after CSC + AHR antagonist exposure. Synergy between CSC and the AHR antagonist in spermatocytes may disrupt the metabolic profile in vitro. Toxic exposures alter energy homeostasis in early stages of male germ cell development, which could contribute to later effects explaining decreases in sperm motility in smokers. PMID:24803506

Adjustable patella grapple versus cannulated screw and cable technique for treatment of transverse patellar fractures.

PubMed

Yan, Ning; Yang, Anli; Liu, Xiaodong; Cai, Feng; Liu, Liang; Chang, Shimin

2014-03-01

Although the cannulated screw and cable (CSC) tension band technique is an effective method for fixation of transverse patellar fractures, it has shortcomings, such as extensive soft tissue damage, osseous substance damage, and complex manipulation. We conducted a retrospective comparison of the adjustable patella grapple (APG) technique and the CSC tension band technique. We retrospectively reviewed 78 patients with transverse patellar fractures (45 in the APG group and 33 in the CSC group). Follow-up was 18 months. Comparison criteria were operation time, fracture reduction, fracture healing time, the knee injury and osteoarthritis outcome score for knee function, and complications. The APG group showed shorter operation time and equal fracture reduction, fracture healing time, and knee function compared with the CSC group. Eleven patients in the APG group experienced skin irritation generated by implants. There was no complication in the CSC group. The APG technique should be considered as an alternative method for treatment of transverse patellar fractures.

Camelina sativa cake improved unsaturated fatty acids in ewe's milk.

PubMed

Szumacher-Strabel, Malgorzata; Cieślak, Adam; Zmora, Pawel; Pers-Kamczyc, Emilia; Bielińska, Sylwia; Stanisz, Marek; Wójtowski, Jacek

2011-08-30

Camelina sativa cake (CSC), a rich source of unsaturated fatty acids, in the case of ruminants, may improve the energy value of a diet and also increase the unsaturated fatty acid content in milk. Effects of basal diet (control), basal diet plus 30 g kg(-1) of CSC in dietary dry matter (DM), basal diet plus 60 g kg(-1) of CSC in dietary dry matter on milk production and the fatty acid composition of ewe's milk with particular emphasis on the monoenes and conjugated isomers of linoleic acid content were examined. Elevated concentration of total monounsaturated fatty acids, the effect of an increase in monounsaturated fatty acids in the trans configuration, as well as the increased content of total polyunsaturated fatty acids, resulted from CSC supplementation. Total saturated fatty acid concentration was decreased. Milk from CSC-supplemented ewes was characterized by increased levels of beneficial nutritional factors, including mono- and n-3 polyunsaturated fatty acids, and was also by lower atherogenic and thrombogenic indices. Taking into consideration all the obtained results and recommended fat concentrations in a daily ruminant ration, we recommend supplementing a dairy ewe's diet with 30 g kg(-1) DM of CSC cake in practice. Copyright © 2011 Society of Chemical Industry.

Fundus autofluorescence imaging patterns in central serous chorioretinopathy according to chronicity.

PubMed

Lee, W J; Lee, J-H; Lee, B R

2016-10-01

PurposeTo investigate the time-period characteristics associated with morphologic changes in central serous chorioretinopathy (CSC) using fundus autofluorescence (FAF).Patients and methodsRetrospective, cross-sectional observational case series. Patients were classified into three groups: acute and chronic according to the onset of subjective symptoms of 6 weeks and sequelae patients who have history and symptoms but no serous retinal detachment (SRD). We compared FAF images to obtain characteristic findings according to the chronicity.ResultsA total of 52 eyes were included in this study. Acute CSC eyes were characterized by decreased FAF intensity at the leakage point in 13/22 eyes (56.5%) and staining patterns with various levels of fluorescence signal (hyperautofluorescent (10 eyes, 43.5%), hypoautofluorescent (1 eye, 4.3%), and minimal changes (12 eyes, 52.2%)) in the area of SRD. In chronic CSC eyes, hyperautofluorescent (14 eyes, 63.6%) or minimal changes (8 eyes, 36.4%) were observed in the area of SRD. Discrete dots with increased FAF intensity were observed in chronic CSC eyes (P<0.001). Eyes with sequelae of CSC had mixed FAF patterns over areas of retinal pigment epithelium (RPE) atrophy in seven eyes (100%, P<0.001)) and descending tracts which showed various FAF intensities according to the RPE and photoreceptor status (P<0.001).ConclusionFAF imaging patterns in CSC eyes differ according to the course of the disease, reflecting RPE and outer retinal changes. Detailed investigation using FAF could help to estimate the duration of CSC and determine the proper treatment modality.

Cigarette smoke-induced cell cycle arrest in spermatocytes [GC-2spd(ts)] is mediated through crosstalk between Ahr-Nrf2 pathway and MAPK signaling.

PubMed

Esakky, Prabagaran; Hansen, Deborah A; Drury, Andrea M; Moley, Kelle H

2015-02-01

Our earlier studies have demonstrated that the cigarette smoke in the form of cigarette smoke condensate (CSC) causes growth arrest of a mouse spermatocyte cell line [GC-2spd(ts)] through activation of the AHR-NRF2 pathway. The present study demonstrates the CSC-activated p38 and ERK MAPK signaling in GC-2spd(ts) via arylhydrocarbon receptor (AHR). Pharmacological inhibition by using AHR-antagonist, or p38 MAPK and ERK (MEK1) inhibitors significantly abrogates CSC-induced growth arrest by AHR and MAPK inactivation. QRT-PCR, western blot, and immunofluorescence of Ahr-target of Nrf2, and stress-inducible growth suppressive Atf3 and E2f4 following treatments indicate a crosstalk among these pathways. Regulation of Atf3 by Nrf2 and Ahr through RNA interference suggests the existence of a cross-regulatory loop between the targets. CSC induction of E2f4 via Atf3 and its regulation by pharmacological inhibitors reveal a possible regulatory mechanism of growth inhibitory CSC. SiRNA silencing of Ahr, Nrf2, Atf3, and E2f4 genes and downregulation of cyclins by CSC corroborate the growth inhibitory effect of cigarette smoke. Thus, the data obtained suggest that the CSC-mediated MAPKs and AHR-NRF2 crosstalks lay the molecular basis for the growth arrest and cell death of spermatocytes. © The Author (2014). Published by Oxford University Press on behalf of Journal of Molecular Cell Biology, IBCB, SIBS, CAS. All rights reserved.

Northwest Climate Science Center: Integrating Regional Research, Conservation and Natural Resource Management

NASA Astrophysics Data System (ADS)

Mote, P.; Bisbal, G.

2012-12-01

The Northwest Climate Science Center (NW CSC) was established in 2010, among the first three of eight regional Climate Science Centers created by the Department of the Interior (DOI). The NW CSC is supported by an academic consortium (Oregon State University, University of Idaho, and the University of Washington), which has the capacity to generate and coordinate decision-relevant science related to climate, thus serving stakeholders across the Pacific Northwest region. The NW CSC has overlapping boundaries with three Landscape Conservation Cooperatives (LCCs): the Great Northern, the Great Basin, and the North Pacific. Collaboration between the NW CSC and these three LCCs addresses the highest priority regional climate science needs of Northwest natural and cultural resource managers. Early in 2012, the NW CSC released its first Strategic Plan for the period 2012-2015. The plan offers a practical blueprint for operation and describes five core services that the NW CSC provides to the Northwest community. These core services emphasize (a) bringing together the regional resource management and science communities to calibrate priorities and ensure efficient integration of climate science resources and tools when addressing practical issues of regional significance; (b) developing and implementing a stakeholder-driven science agenda which highlights the NW CSC's regional leadership in generating scenarios of the future environment of the NW; (c) supporting and training graduate students at the three consortium universities, including through an annual 'Climate science boot camp'; (d) providing a platform for effective climate-change-related communication among scientists, resource managers, and the general public; and (e) national leadership in data management and climate scenario development.

The effect of artificial seawater on SERS spectra of amino acids-Ag colloids: an experiment of prebiotic chemistry.

PubMed

Nascimento, Fernanda C; Carneiro, Cristine E A; de Santana, Henrique; Zaia, Dimas A M

2014-01-24

The large enhancement of signal observed in surface enhanced Raman spectroscopy (SERS) could be helpful for identifying amino acids on the surface of other planets, in particular for Mars, as well as in prebiotic chemistry experiments of interaction minerals/amino acids. This paper reports the effect of several substances (NaCl, MgCl2, KBr, CaSO4, K2SO4, MgSO4, KI, NH4Cl, SrCl2, CaCl2, Na2SO4, KOH, NaOH, H3BO3) on the SERS spectra of colloid of sodium citrate-CSC and colloid of sodium borohydride-CSB. The effect of four different artificial seawaters and these artificial seawaters plus amino acids (α-Ala-alanine, Gly-glycine, Cys-cysteine, AIB-2-aminoisobutiric acid) on SERS spectra using both CSC and CSB was also studied. For CSC, the effect of water, after dilution of the colloid, was the appearance of several absorption bands belonging to sodium citrate in the SERS spectrum. In general, artificial seawaters enhanced several bands in SERS spectra using CSC and CSB and CSC was more sensitive to those artificial seawaters than CSB. The identification of Gly, α-Ala and AIB using CSC or CSB was not possible because several bands belonging to artificial seawaters, sodium citrate or sodium borohydride were enhanced. On the other hand, artificial seawaters did not interfere in the SERS spectra of Cys using CSC or CSB, although the interaction of Cys with each colloid was different. For CSC the band at 2568 cm(-1) (S-H stretching) of Cys vanished and for CSB the intensity of this band decreased, indicating the -SH of Cys was bonded to Ag to form -S-Ag. Thus SERS spectroscopy could be used for Cys detection on Mars soils using Mars land rovers as well as to study the interaction between Cys and minerals in prebiotic chemistry experiments. Copyright © 2013 Elsevier B.V. All rights reserved.

The effect of artificial seawater on SERS spectra of amino acids-Ag colloids: An experiment of prebiotic chemistry

NASA Astrophysics Data System (ADS)

Nascimento, Fernanda C.; Carneiro, Cristine E. A.; Santana, Henrique de; Zaia, Dimas A. M.

2014-01-01

The large enhancement of signal observed in surface enhanced Raman spectroscopy (SERS) could be helpful for identifying amino acids on the surface of other planets, in particular for Mars, as well as in prebiotic chemistry experiments of interaction minerals/amino acids. This paper reports the effect of several substances (NaCl, MgCl2, KBr, CaSO4, K2SO4, MgSO4, KI, NH4Cl, SrCl2, CaCl2, Na2SO4, KOH, NaOH, H3BO3) on the SERS spectra of colloid of sodium citrate-CSC and colloid of sodium borohydride-CSB. The effect of four different artificial seawaters and these artificial seawaters plus amino acids (α-Ala-alanine, Gly-glycine, Cys-cysteine, AIB-2-aminoisobutiric acid) on SERS spectra using both CSC and CSB was also studied. For CSC, the effect of water, after dilution of the colloid, was the appearance of several absorption bands belonging to sodium citrate in the SERS spectrum. In general, artificial seawaters enhanced several bands in SERS spectra using CSC and CSB and CSC was more sensitive to those artificial seawaters than CSB. The identification of Gly, α-Ala and AIB using CSC or CSB was not possible because several bands belonging to artificial seawaters, sodium citrate or sodium borohydride were enhanced. On the other hand, artificial seawaters did not interfere in the SERS spectra of Cys using CSC or CSB, although the interaction of Cys with each colloid was different. For CSC the band at 2568 cm-1 (S-H stretching) of Cys vanished and for CSB the intensity of this band decreased, indicating the -SH of Cys was bonded to Ag to form -S-Ag. Thus SERS spectroscopy could be used for Cys detection on Mars soils using Mars land rovers as well as to study the interaction between Cys and minerals in prebiotic chemistry experiments.

CK2 phosphorylates and inhibits TAp73 tumor suppressor function to promote expression of cancer stem cell genes and phenotype in head and neck cancer.

PubMed

Lu, Hai; Yan, Carol; Quan, Xin Xin; Yang, Xinping; Zhang, Jialing; Bian, Yansong; Chen, Zhong; Van Waes, Carter

2014-10-01

Cancer stem cells (CSC) and genes have been linked to cancer development and therapeutic resistance, but the signaling mechanisms regulating CSC genes and phenotype are incompletely understood. CK2 has emerged as a key signal serine/threonine kinase that modulates diverse signal cascades regulating cell fate and growth. We previously showed that CK2 is often aberrantly expressed and activated in head and neck squamous cell carcinomas (HNSCC), concomitantly with mutant (mt) tumor suppressor TP53, and inactivation of its family member, TAp73. Unexpectedly, we observed that classical stem cell genes Nanog, Sox2, and Oct4, are overexpressed in HNSCC with inactivated TAp73 and mtTP53. However, the potential relationship between CK2, TAp73 inactivation, and CSC phenotype is unknown. We reveal that inhibition of CK2 by pharmacologic inhibitors or siRNA inhibits the expression of CSC genes and side population (SP), while enhancing TAp73 mRNA and protein expression. Conversely, CK2 inhibitor attenuation of CSC protein expression and the SP by was abrogated by TAp73 siRNA. Bioinformatic analysis uncovered a single predicted CK2 threonine phosphorylation site (T27) within the N-terminal transactivation domain of TAp73. Nuclear CK2 and TAp73 interaction, confirmed by co-immunoprecipitation, was attenuated by CK2 inhibitor, or a T27A point-mutation of this predicted CK2 threonine phospho-acceptor site of TAp73. Further, T27A mutation attenuated phosphorylation, while enhancing TAp73 function in repressing CSC gene expression and SP cells. A new CK2 inhibitor, CX-4945, inhibited CSC related SP cells, clonogenic survival, and spheroid formation. Our study unveils a novel regulatory mechanism whereby aberrant CK2 signaling inhibits TAp73 to promote the expression of CSC genes and phenotype.

Differential discriminative-stimulus effects of cigarette smoke condensate and nicotine in nicotine-discriminating rats.

PubMed

Lee, Jun-Yeob; Choi, Mee Jung; Choe, Eun Sang; Lee, Young-Ju; Seo, Joung-Wook; Yoon, Seong Shoon

2016-06-01

Although it is widely accepted that nicotine plays a key role in tobacco dependence, nicotine alone cannot account for all of the pharmacological effects associated with cigarette smoke found in preclinical models. Thus, the present study aimed to determine the differential effects of the interoceptive cues of nicotine alone versus those of cigarette smoke condensate (CSC) in nicotine-trained rats. First, the rats were trained to discriminate nicotine (0.4mg/kg, subcutaneous [s.c.]) from saline in a two-lever drug discrimination paradigm. Then, to clarify the different neuropharmacological mechanisms underlying the discriminative-stimulus effects in the nicotine and CSC in nicotine-trained rats, either the α4β2 nicotinic acetylcholine receptor (nAChR) antagonist dihydro-β-erythroidine (DHβE; 0.3-1.0mg/kg, s.c.) or the α7 nAChR antagonist methyllycaconitine citrate (MLA; 5-10mg/kg, intraperitoneal [i.p.]) was administered prior to the injection of either nicotine or CSC. Separate set of experiments was performed to compare the duration of action of the discriminative-stimulus effects of CSC and nicotine. CSC exhibited a dose-dependent nicotine generalization, and interestingly, 1.0mg/kg of DHβE antagonized the discriminative effects of nicotine (0.4mg/kg) but not CSC (0.4mg/kg nicotine content). However, pretreatment with MLA had no effect. In the time-course study, CSC had a relatively longer half-life in terms of the discriminative-stimulus effects compared with nicotine alone. Taken together, the present findings indicate that CSC has a distinct influence on interoceptive effects relative to nicotine alone and that these differential effects might be mediated, at least in part, by the α4β2, but not the α7, nAChR. Copyright © 2016 Elsevier B.V. All rights reserved.

Lung volume changes during cleaning of closed endotracheal suction catheters: a randomized crossover study using electrical impedance tomography.

PubMed

Corley, Amanda; Sharpe, Nicola; Caruana, Lawrence R; Spooner, Amy J; Fraser, John F

2014-04-01

Airway suctioning in mechanically ventilated patients is required to maintain airway patency. Closed suction catheters (CSCs) minimize lung volume loss during suctioning but require cleaning post-suction. Despite their widespread use, there is no published evidence examining lung volumes during CSC cleaning. The study objectives were to quantify lung volume changes during CSC cleaning and to determine whether these changes were preventable using a CSC with a valve in situ between the airway and catheter cleaning chamber. This prospective randomized crossover study was conducted in a metropolitan tertiary ICU. Ten patients mechanically ventilated via volume-controlled synchronized intermittent mandatory ventilation (SIMV-VC) and requiring manual hyperinflation (MHI) were included in this study. CSC cleaning was performed using 2 different brands of CSC (one with a valve [Ballard Trach Care 72, Kimberly-Clark, Roswell, Georgia] and one without [Portex Steri-Cath DL, Smiths Medical, Dublin, Ohio]). The maneuvers were performed during both SIMV-VC and MHI. Lung volume change was measured via impedance change using electrical impedance tomography. A mixed model was used to compare the estimated means. During cleaning of the valveless CSC, significant decreases in lung impedance occurred during MHI (-2563 impedance units, 95% CI 2213-2913, P < .001), and significant increases in lung impedance occurred during SIMV (762 impedance units, 95% CI 452-1072, P < .001). In contrast, cleaning of the CSC with a valve in situ resulted in non-significant lung volume changes and maintenance of normal ventilation during MHI and SIMV-VC, respectively (188 impedance units, 95% CI -136 to 511, P = .22; and 22 impedance units, 95% CI -342 to 299, P = .89). When there is no valve between the airway and suction catheter, cleaning of the CSC results in significant derangements in lung volume. Therefore, the presence of such a valve should be considered essential in preserving lung volumes and uninterrupted ventilation in mechanically ventilated patients.

WE-E-BRE-10: Level of Breast Cancer Stem Cell Correlated with Tumor Radioresistence: An Indication for Individualized Breast Cancer Therapy Adapted to Cancer Stem Cell Fractions

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

Qi, S; Pajonk, F; McCloskey, S

2014-06-15

Purposes: The presence of cancer stem cells (CSCs) in a solid tumor could result in poor tumor control probability. The purposes are to study CSC radiosensitivity parameters α and β and their correlation to CSC levels to understand the underlying radioresistance mechanisms and enable individualized treatment design. Methods: Four established breast cancer cell lines (MCF-7, T47D, MDA-MB-231, and SUM159PT) were irradiated in vitro using single radiation doses of 0, 2, 4, 6, 8 or 10 Gy. The fractions of CSCs in each cell lines were determined using cancer stem cell markers. Mammosphere assays were also performed to better estimate themore » number of CSCs and represent the CSC repopulation in a human solid tumor. The measured cell surviving fractions were fitted using the Linear-quadratic (LQ) model with independent fitting parameters: α-TC, β-TC (TCs), α-CSC, β-CSC (CSCs), and fs (the percentage of CSCs in each sample). Results: The measured fs increased following the irradiation by MCF-7 (0.1%), T47D (0.9%), MDA-MB-231 (1.18%) and SUM159T (2.46%), while decreasing surviving curve slopes were observed, indicating greater radioresistance, in the opposite order. The fitting yielded the radiosensitive parameters for the MCF-7: α-TC=0.1±0.2Gy{sup −1}, β-TC= 0.08 ±0.14Gy{sup −2}, α-CSC=0.04±0.07Gy{sup −1}, β-CSC =0.02±0.3Gy{sup −2}; for the SUM159PT, α-TC=0.08±0.25 Gy{sup −1}, β-TC=0.02±0.02Gy{sup −2}, α-CSC=0.04±0.18Gy{sup −1}, β-CSC =0.004±0.24Gy{sup −2}. In the mammosphere assay, where fs were higher than the corresponding cell line assays, there was almost no shoulder found in the surviving curves (more radioresistant in mammosphere assays) yielding β-CSC of approximately 0. Conclusion: Breast cancer stem cells were more radioresistant characterized by smaller α and β values compared to differentiated breast cancer cells. Percentage of breast cancer stem cells strongly correlated to overall tumor radioresistance. This observation suggested the feasibility of individualized radiotherapy prescription based on the fractions of cancer stem cells found in biopsy.« less

Comparative study of cryogen spray cooling with R-134a and R-404a: implications for laser treatment of dark human skin

NASA Astrophysics Data System (ADS)

Dai, Tianhong; Yaseen, Mohammad A.; Diagaradjane, Parmeswaran; Chang, David W.; Anvari, Bahman

2006-07-01

Cutaneous laser treatment in dark skin patients is challenging due to significant light absorption by the melanin at the basal layer of epidermis, which can result in irreversible nonspecific thermal injury to the epidermis. Cryogen spray cooling (CSC) with R-134a (boiling point ≈ -26.2°C at 1 atm), which is currently used during cutaneous laser treatment, has shown poor efficacy in protecting dark human skin. We investigated the potential of CSC with R-404a (boiling point ≈ -46.5°C at 1 atm), which has a lower boiling point than R-134a, for improved therapeutic outcome in dark human skin at three levels: in vitro (epoxy resin skin phantom), ex vivo (normal dark human skin sample), and in vivo (skin of the rabbit external ear). The skin phantom was used to acquire the surface and internal temperature profiles in response to CSC with R-134a or R-404a at various spurt durations, based upon which CSC-induced heat removal from the skin phantom was estimated using an algorithm that solved a one-dimensional inverse heat conduction problem. CSC with R-404a increased the temperature reductions within the phantom and subsequently the amount of heat removal from the phantom in comparison to that with R-134a. Normal ex vivo Fitzpatrick types V-VI human skin samples were used to investigate the thermal response of dark human skin epidermis to CSC (R-134a or R-404a) at various spurt durations in conjunction with 595-nm pulsed dye laser irradiation at various radiant exposures. Cryogen R-404a increased the threshold radiant exposures for irreversible thermal injury to the epidermis in dark pigmentation skin. No obvious CSC-induced morphological changes to human skin was observed when sprayed with R404-a spurts using durations up to 300 ms. In vivo rabbit ear vasculature was used as a model of cutaneous anomalies to assess the influences of CSC (with R-134a or R-404a) on the photothermolysis of dermal blood vessels. CSC (R-134a or R-404a) with the spurt durations of 100 to 300 ms increased the most superficial depth of thermally damaged dermal blood vessel compared with the sites without CSC, implying possible nonspecific cooling of superficial dermal blood vessels by the cryogen spurts with the settings applied.

U.S. Department of the Interior South Central Climate Science Center strategic science plan, 2013--18

USGS Publications Warehouse

Winton, Kim T.; Dalton, Melinda S.; Shipp, Allison A.

2013-01-01

The Department of the Interior (DOI) recognizes and embraces the unprecedented challenges of maintaining our Nation’s rich natural and cultural resources in the 21st century. The magnitude of these challenges demands that the conservation community work together to develop integrated adaptation and mitigation strategies that collectively address the impacts of climate change and other landscape-scale stressors. On September 14, 2009, DOI Secretary Ken Salazar signed Secretarial Order 3289 (amended February 22, 2010) entitled, “Addressing the Impacts of Climate Change on America’s Water, Land, and Other Natural and Cultural Resources.” The Order establishes the foundation for two partner-based conservation science entities to address these unprecedented challenges: Climate Science Centers (CSCs and Landscape Conservation Cooperatives (LCCs). CSCs and LCCs are the Department-wide approach for applying scientific tools to increase understanding of climate change and to coordinate an effective response to its impacts on tribes and the land, water, ocean, fish and wildlife, and cultural-heritage resources that DOI manages. Eight CSCs have been established and are managed through the U.S. Geological Survey (USGS) National Climate Change and Wildlife Science Center (NCCWSC); each CSC works in close collaboration with their neighboring CSCs, as well as those across the Nation, to ensure the best and most efficient science is produced. The South Central CSC was established in 2012 through a cooperative agreement with the University of Oklahoma, Texas Tech University, Louisiana State University, the Chickasaw Nation, the Choctaw Nation of Oklahoma, Oklahoma State University, and NOAA’s Geophysical Fluid Dynamics Lab; hereafter termed the ”Consortium” of the South Central CSC. The Consortium has a broad expertise in the physical, biological, natural, and social sciences to address impacts of climate change on land, water, fish and wildlife, ocean, coastal, and cultural resources. The South Central CSC will provide scientific information, tools, and techniques that managers and other parties interested in land, water, wildlife, and cultural resources can use to anticipate, monitor, and adapt to climate change, actively engaging LCCs and other partners in translating science into management decisions. This document is the first Strategic Science Plan for the South Central CSC (2013-18). Using the January 2011 DOI guidance as a model, this document (1) describes the role and interactions of the South Central CSC among partners and stakeholders including Federal, State, and non-governmental organizations throughout the region; (2) describes a concept of what the center will provide to its partners; (3) defines a context for climate impacts in the south central United States; and (4) establishes the science priorities the center will address through research. Science priorities are currently organized as immediate or future research needs; however, this document is intended to be reevaluated and modified as partner needs change and as scientific work progresses.

Hyaluronan Production Regulates Metabolic and Cancer Stem-like Properties of Breast Cancer Cells via Hexosamine Biosynthetic Pathway-coupled HIF-1 Signaling*

PubMed Central

Chanmee, Theerawut; Ontong, Pawared; Izumikawa, Tomomi; Higashide, Miho; Mochizuki, Nobutoshi; Chokchaitaweesuk, Chatchadawalai; Khansai, Manatsanan; Nakajima, Kazuki; Kakizaki, Ikuko; Kongtawelert, Prachya; Taniguchi, Naoyuki; Itano, Naoki

2016-01-01

Cancer stem cells (CSCs) represent a small subpopulation of self-renewing oncogenic cells. As in many other stem cells, metabolic reprogramming has been implicated to be a key characteristic of CSCs. However, little is known about how the metabolic features of cancer cells are controlled to orchestrate their CSC-like properties. We recently demonstrated that hyaluronan (HA) overproduction allowed plastic cancer cells to revert to stem cell states. Here, we adopted stable isotope-assisted tracing and mass spectrometry profiling to elucidate the metabolic features of HA-overproducing breast cancer cells. These integrated approaches disclosed an acceleration of metabolic flux in the hexosamine biosynthetic pathway (HBP). A metabolic shift toward glycolysis was also evident by quantitative targeted metabolomics, which was validated by the expression profiles of key glycolytic enzymes. Forced expression of glutamine:fructose-6-phosphate amidotransferase 1 (GFAT1), an HBP rate-limiting enzyme, resembled the results of HA overproduction with regard to HIF-1α accumulation and glycolytic program, whereas GFAT1 inhibition significantly decreased HIF-1α protein level in HA-overproducing cancer cells. Moreover, inhibition of the HBP-HIF-1 axis abrogated HA-driven glycolytic enhancement and reduced the CSC-like subpopulation. Taken together, our results provide compelling evidence that HA production regulates the metabolic and CSC-like properties of breast cancer cells via HBP-coupled HIF-1 signaling. PMID:27758869

Comparison of subfoveal choroidal thickness in healthy pregnancy and pre-eclampsia

PubMed Central

Kim, J W; Park, M H; Kim, Y J; Kim, Y T

2016-01-01

Purpose Pregnancy is a known predisposing factor for central serous chorioretinopathy (CSC). Choroidal thickness (CT) increases in patients with CSC. This study was designed to evaluate CT in pregnant women. Patients and methods This was a prospective study. Fourteen healthy pregnant women and seven patients with pre-eclampsia were included. Twenty-one normal subjects were also recruited. CT was measured using enhanced-depth imaging optical coherence tomography. Results The mean CT of normal subjects, healthy pregnant women and patients with pre-eclampsia were 264.95±21.03, 274.23±29.30 and 389.79±25.13 μm, respectively (normal subjects vs healthy gravidas: P>0.05; normal subjects vs pre-eclampsia: P<0.001; healthy gravidas vs pre-eclampsia: P<0.001). CT decreased from 381.05±22.96 μm to 335.17±9.97 μm 1 week after delivery in patients with pre-eclampsia. Conclusions Pregnancy itself did not increase CT, whereas pre-eclampsia did appear to result in increased CT. This suggests that additional unknown factors induce hyperpermeability in pregnant women. PMID:26541086

Regional climate projections for the MENA-CORDEX domain: analysis of projected temperature and precipitation changes

NASA Astrophysics Data System (ADS)

Hänsler, Andreas; Weber, Torsten; Eggert, Bastian; Saeed, Fahad; Jacob, Daniela

2014-05-01

Within the CORDEX initiative a multi-model suite of regionalized climate change information will be made available for several regions of the world. The German Climate Service Center (CSC) is taking part in this initiative by applying the regional climate model REMO to downscale global climate projections of different coupled general circulation models (GCMs) for several CORDEX domains. Also for the MENA-CORDEX domain, a set of regional climate change projections has been established at the CSC by downscaling CMIP5 projections of the Max-Planck-Institute Earth System Model (MPI-ESM) for the scenarios RCP4.5 and RCP8.5 with the regional model REMO for the time period from 1950 to 2100 to a horizontal resolution of 0.44 degree. In this study we investigate projected changes in future climate conditions over the domain towards the end of the 21st century. Focus in the analysis is given to projected changes in the temperature and rainfall characteristics and their differences for the two scenarios will be highlighted.

Cancer stem cell-related gene expression as a potential biomarker of response for first-in-class imipridone ONC201 in solid tumors.

PubMed

Prabhu, Varun V; Lulla, Amriti R; Madhukar, Neel S; Ralff, Marie D; Zhao, Dan; Kline, Christina Leah B; Van den Heuvel, A Pieter J; Lev, Avital; Garnett, Mathew J; McDermott, Ultan; Benes, Cyril H; Batchelor, Tracy T; Chi, Andrew S; Elemento, Olivier; Allen, Joshua E; El-Deiry, Wafik S

2017-01-01

Cancer stem cells (CSCs) correlate with recurrence, metastasis and poor survival in clinical studies. Encouraging results from clinical trials of CSC inhibitors have further validated CSCs as therapeutic targets. ONC201 is a first-in-class small molecule imipridone in Phase I/II clinical trials for advanced cancer. We have previously shown that ONC201 targets self-renewing, chemotherapy-resistant colorectal CSCs via Akt/ERK inhibition and DR5/TRAIL induction. In this study, we demonstrate that the anti-CSC effects of ONC201 involve early changes in stem cell-related gene expression prior to tumor cell death induction. A targeted network analysis of gene expression profiles in colorectal cancer cells revealed that ONC201 downregulates stem cell pathways such as Wnt signaling and modulates genes (ID1, ID2, ID3 and ALDH7A1) known to regulate self-renewal in colorectal, prostate cancer and glioblastoma. ONC201-mediated changes in CSC-related gene expression were validated at the RNA and protein level for each tumor type. Accordingly, we observed inhibition of self-renewal and CSC markers in prostate cancer cell lines and patient-derived glioblastoma cells upon ONC201 treatment. Interestingly, ONC201-mediated CSC depletion does not occur in colorectal cancer cells with acquired resistance to ONC201. Finally, we observed that basal expression of CSC-related genes (ID1, CD44, HES7 and TCF3) significantly correlate with ONC201 efficacy in >1000 cancer cell lines and combining the expression of multiple genes leads to a stronger overall prediction. These proof-of-concept studies provide a rationale for testing CSC expression at the RNA and protein level as a predictive and pharmacodynamic biomarker of ONC201 response in ongoing clinical studies.

Cancer stem cell-related gene expression as a potential biomarker of response for first-in-class imipridone ONC201 in solid tumors

PubMed Central

Zhao, Dan; Kline, Christina Leah B.; Van den Heuvel, A. Pieter J.; Lev, Avital; Garnett, Mathew J.; McDermott, Ultan; Benes, Cyril H.; Batchelor, Tracy T.; Chi, Andrew S.; Elemento, Olivier; Allen, Joshua E.

2017-01-01

Cancer stem cells (CSCs) correlate with recurrence, metastasis and poor survival in clinical studies. Encouraging results from clinical trials of CSC inhibitors have further validated CSCs as therapeutic targets. ONC201 is a first-in-class small molecule imipridone in Phase I/II clinical trials for advanced cancer. We have previously shown that ONC201 targets self-renewing, chemotherapy-resistant colorectal CSCs via Akt/ERK inhibition and DR5/TRAIL induction. In this study, we demonstrate that the anti-CSC effects of ONC201 involve early changes in stem cell-related gene expression prior to tumor cell death induction. A targeted network analysis of gene expression profiles in colorectal cancer cells revealed that ONC201 downregulates stem cell pathways such as Wnt signaling and modulates genes (ID1, ID2, ID3 and ALDH7A1) known to regulate self-renewal in colorectal, prostate cancer and glioblastoma. ONC201-mediated changes in CSC-related gene expression were validated at the RNA and protein level for each tumor type. Accordingly, we observed inhibition of self-renewal and CSC markers in prostate cancer cell lines and patient-derived glioblastoma cells upon ONC201 treatment. Interestingly, ONC201-mediated CSC depletion does not occur in colorectal cancer cells with acquired resistance to ONC201. Finally, we observed that basal expression of CSC-related genes (ID1, CD44, HES7 and TCF3) significantly correlate with ONC201 efficacy in >1000 cancer cell lines and combining the expression of multiple genes leads to a stronger overall prediction. These proof-of-concept studies provide a rationale for testing CSC expression at the RNA and protein level as a predictive and pharmacodynamic biomarker of ONC201 response in ongoing clinical studies. PMID:28767654

Ciprofloxacin mediates cancer stem cell phenotypes in lung cancer cells through caveolin-1-dependent mechanism.

PubMed

Phiboonchaiyanan, Preeyaporn Plaimee; Kiratipaiboon, Chayanin; Chanvorachote, Pithi

2016-04-25

Cancer stem cells (CSCs), a subpopulation of cancer cells with high aggressive behaviors, have been identified in many types of cancer including lung cancer as one of the key mediators driving cancer progression and metastasis. Here, we have reported for the first time that ciprofloxacin (CIP), a widely used anti-microbial drug, has a potentiating effect on CSC-like features in human non-small cell lung cancer (NSCLC) cells. CIP treatment promoted CSC-like phenotypes, including enhanced anchorage-independent growth and spheroid formation. The known lung CSC markers: CD133, CD44, ABCG2 and ALDH1A1 were found to be significantly increased, while the factors involving in epithelial to mesenchymal transition (EMT): Slug and Snail, were depleted. Also, self-renewal transcription factors Oct-4 and Nanog were found to be up-regulated in CIP-treated cells. The treatment of CIP on CSC-rich populations obtained from secondary spheroids resulted in the further increase of CSC markers. In addition, we have proven that the mechanistic insight of the CIP induced stemness is through Caveolin-1 (Cav-1)-dependent mechanism. The specific suppression of Cav-1 by stably transfected Cav-1 shRNA plasmid dramatically reduced the effect of CIP on CSC markers as well as the CIP-induced spheroid formation ability. Cav-1 was shown to activate protein kinase B (Akt) and extracellular signal-regulated kinase (ERK) pathways in CSC-rich population; however, such an effect was rarely found in the main lung cancer cells population. These findings reveal a novel effect of CIP in positively regulating CSCs in lung cancer cells via the activation of Cav-1, Akt and ERK, and may provoke the awareness of appropriate therapeutic strategy in cancer patients. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Estimated Impact of Emergency Medical Service Triage of Stroke Patients on Comprehensive Stroke Centers: An Urban Population-Based Study.

PubMed

Katz, Brian S; Adeoye, Opeolu; Sucharew, Heidi; Broderick, Joseph P; McMullan, Jason; Khatri, Pooja; Widener, Michael; Alwell, Kathleen S; Moomaw, Charles J; Kissela, Brett M; Flaherty, Matthew L; Woo, Daniel; Ferioli, Simona; Mackey, Jason; Martini, Sharyl; De Los Rios la Rosa, Felipe; Kleindorfer, Dawn O

2017-08-01

The American Stroke Association recommends that Emergency Medical Service bypass acute stroke-ready hospital (ASRH)/primary stroke center (PSC) for comprehensive stroke centers (CSCs) when transporting appropriate stroke patients, if the additional travel time is ≤15 minutes. However, data on additional transport time and the effect on hospital census remain unknown. Stroke patients ≥20 years old who were transported from home to an ASRH/PSC or CSC via Emergency Medical Service in 2010 were identified in the Greater Cincinnati area population of 1.3 million. Addresses of all patients' residences and hospitals were geocoded, and estimated travel times were calculated. We estimated the mean differences between the travel time for patients taken to an ASRH/PSC and the theoretical time had they been transported directly to the region's CSC. Of 929 patients with geocoded addresses, 806 were transported via Emergency Medical Service directly to an ASRH/PSC. Mean additional travel time of direct transport to the CSC, compared with transport to an ASRH/PSC, was 7.9±6.8 minutes; 85% would have ≤15 minutes added transport time. Triage of all stroke patients to the CSC would have added 727 patients to the CSC's census in 2010. Limiting triage to the CSC to patients with National Institutes of Health Stroke Scale score of ≥10 within 6 hours of onset would have added 116 patients (2.2 per week) to the CSC's annual census. Emergency Medical Service triage to CSCs based on stroke severity and symptom duration may be feasible. The impact on stroke systems of care and patient outcomes remains to be determined and requires prospective evaluation. © 2017 American Heart Association, Inc.

Wnt5a Is Associated with Cigarette Smoke-Related Lung Carcinogenesis via Protein Kinase C

PubMed Central

Sung, Jae Sook; Ju, Hyun Jung; Kim, Hyun Kyung; Park, Kyong Hwa; Lee, Jong Won; Koh, In Song; Kim, Yeul Hong

2013-01-01

Wnt5a is overexpressed during the progression of human non-small cell lung cancer. However, the roles of Wnt5a during smoking-related lung carcinogenesis have not been clearly elucidated. We investigated the associations between Wnt5a and the early development of cigarette smoke related lung cancer using human bronchial epithelial (HBE) cells (NHBE, BEAS-2B, 1799, 1198 and 1170I) at different malignant stages established by exposure to cigarette smoke condensate (CSC). Abnormal up-regulation of Wnt5a mRNA and proteins was detected in CSC-exposed transformed 1198 and tumorigenic 1170I cells as compared with other non-CSC exposed HBE cells. Tumor tissues obtained from smokers showed higher Wnt5a expressions than matched normal tissues. In non-CSC exposed 1799 cells, treatment of recombinant Wnt5a caused the activations of PKC and Akt, and the blockage of Wnt5a and PKC significantly decreased the viabilities of CSC-transformed 1198 cells expressing high levels of Wnt5a. This reduced cell survival rate was associated with increased apoptosis via the down-regulation of Bcl2 and the induction of cleaved poly ADP-ribose polymerase. Moreover, CSC-treated 1799 cells showed induction of Wnt5a expression and enhanced colony-forming capacity. The CSC-induced colony forming efficiency was suppressed by the co-incubation with a PKC inhibitor. In conclusion, these results suggest that cigarette smoke induces Wnt5a-coupled PKC activity during lung carcinogenesis, which causes Akt activity and anti-apoptosis in lung cancer. Therefore, current study provides novel clues for the crucial role of Wnt5a in the smoking-related lung carcinogenesis. PMID:23349696

Wnt5a is associated with cigarette smoke-related lung carcinogenesis via protein kinase C.

PubMed

Whang, Young Mi; Jo, Ukhyun; Sung, Jae Sook; Ju, Hyun Jung; Kim, Hyun Kyung; Park, Kyong Hwa; Lee, Jong Won; Koh, In Song; Kim, Yeul Hong

2013-01-01

Wnt5a is overexpressed during the progression of human non-small cell lung cancer. However, the roles of Wnt5a during smoking-related lung carcinogenesis have not been clearly elucidated. We investigated the associations between Wnt5a and the early development of cigarette smoke related lung cancer using human bronchial epithelial (HBE) cells (NHBE, BEAS-2B, 1799, 1198 and 1170I) at different malignant stages established by exposure to cigarette smoke condensate (CSC). Abnormal up-regulation of Wnt5a mRNA and proteins was detected in CSC-exposed transformed 1198 and tumorigenic 1170I cells as compared with other non-CSC exposed HBE cells. Tumor tissues obtained from smokers showed higher Wnt5a expressions than matched normal tissues. In non-CSC exposed 1799 cells, treatment of recombinant Wnt5a caused the activations of PKC and Akt, and the blockage of Wnt5a and PKC significantly decreased the viabilities of CSC-transformed 1198 cells expressing high levels of Wnt5a. This reduced cell survival rate was associated with increased apoptosis via the down-regulation of Bcl2 and the induction of cleaved poly ADP-ribose polymerase. Moreover, CSC-treated 1799 cells showed induction of Wnt5a expression and enhanced colony-forming capacity. The CSC-induced colony forming efficiency was suppressed by the co-incubation with a PKC inhibitor. In conclusion, these results suggest that cigarette smoke induces Wnt5a-coupled PKC activity during lung carcinogenesis, which causes Akt activity and anti-apoptosis in lung cancer. Therefore, current study provides novel clues for the crucial role of Wnt5a in the smoking-related lung carcinogenesis.

Autologous c-Kit+ Mesenchymal Stem Cell Injections Provide Superior Therapeutic Benefit as Compared to c-Kit+ Cardiac-Derived Stem Cells in a Feline Model of Isoproterenol-Induced Cardiomyopathy.

PubMed

Taghavi, Sharven; Sharp, Thomas E; Duran, Jason M; Makarewich, Catherine A; Berretta, Remus M; Starosta, Tim; Kubo, Hajime; Barbe, Mary; Houser, Steven R

2015-10-01

Cardiac- (CSC) and mesenchymal-derived (MSC) CD117+ isolated stem cells improve cardiac function after injury. However, no study has compared the therapeutic benefit of these cells when used autologously. MSCs and CSCs were isolated on day 0. Cardiomyopathy was induced (day 28) by infusion of L-isoproterenol (1,100 ug/kg/hour) from Alzet minipumps for 10 days. Bromodeoxyuridine (BrdU) was infused via minipumps (50 mg/mL) to identify proliferative cells during the injury phase. Following injury (day 38), autologous CSC (n = 7) and MSC (n = 4) were delivered by intracoronary injection. These animals were compared to those receiving sham injections by echocardiography, invasive hemodynamics, and immunohistochemistry. Fractional shortening improved with CSC (26.9 ± 1.1% vs. 16.1 ± 0.2%, p = 0.01) and MSC (25.1 ± 0.2% vs. 12.1 ± 0.5%, p = 0.01) as compared to shams. MSC were superior to CSC in improving left ventricle end-diastolic (LVED) volume (37.7 ± 3.1% vs. 19.9 ± 9.4%, p = 0.03) and ejection fraction (27.7 ± 0.1% vs. 19.9 ± 0.4%, p = 0.02). LVED pressure was less in MSC (6.3 ± 1.3 mmHg) as compared to CSC (9.3 ± 0.7 mmHg) and sham (13.3 ± 0.7); p = 0.01. LV BrdU+ myocytes were higher in MSC (0.17 ± 0.03%) than CSC (0.09 ± 0.01%) and sham (0.06 ± 01%); p < 0.001. Both CD117+ isolated CSC and MSC therapy improve cardiac function and attenuate pathological remodeling. However, MSC appear to confer additional benefit. © 2015 Wiley Periodicals, Inc.

Cigarette smoke-induced cell death of a spermatocyte cell line can be prevented by inactivating the Aryl hydrocarbon receptor

PubMed Central

Esakky, P; Hansen, D A; Drury, A M; Cusumano, A; Moley, K H

2015-01-01

Cigarette smoke exposure causes germ cell death during spermatogenesis. Our earlier studies demonstrated that cigarette smoke condensate (CSC) causes spermatocyte cell death in vivo and growth arrest of the mouse spermatocyte cell line (GC-2spd(ts)) in vitro via the aryl hydrocarbon receptor (AHR). We hypothesize here that inactivation of AHR could prevent the CSC-induced cell death in spermatocytes. We demonstrate that CSC exposure generates oxidative stress, which differentially regulates mitochondrial apoptosis in GC-2spd(ts) and wild type (WT) and AHR knockout (AHR-KO) mouse embryonic fibroblasts (MEFs). SiRNA-mediated silencing of Ahr augments the extent of CSC-mediated cellular damage while complementing the AHR-knockout condition. Pharmacological inhibition using the AHR-antagonist (CH223191) modulates the CSC-altered expression of apoptotic proteins and significantly abrogates DNA fragmentation though the cleavage of PARP appears AHR independent. Pretreatment with CH223191 at concentrations above 50 μM significantly prevents the CSC-induced activation of caspase-3/7 and externalization of phosphatidylserine in the plasma membrane. However, MAPK inhibitors alone or together with CH223191 could not prevent the membrane damage upon CSC addition and the caspase-3/7 activation and membrane damage in AHR-deficient MEF indicates the interplay of multiple cell signaling and cytoprotective ability of AHR. Thus the data obtained on one hand signifies the protective role of AHR in maintaining normal cellular homeostasis and the other, could be a potential prophylactic therapeutic target to promote cell survival and growth under cigarette smoke exposed environment by receptor antagonism via CH223191-like mechanism. Antagonist-mediated inactivation of the aryl hydrocarbon receptor blocks downstream events leading to cigarette smoke-induced cell death of a spermatocyte cell line. PMID:27551479

Cancer stem cell-like cells from a single cell of oral squamous carcinoma cell lines

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

Felthaus, O.; Department of Oral and Maxillofacial Surgery, University of Regensburg; Ettl, T.

2011-04-01

Research highlights: {yields} Four oral squamous cancer cell lines (OSCCL) were analyzed for cancer stem cells (CSCs). {yields} Single cell derived colonies of OSCCL express CSC-marker CD133 differentially. {yields} Monoclonal cell lines showed reduced sensitivity for Paclitaxel. {yields} In situ CD133{sup +} cells are slow cycling (Ki67-) indicating a reduced drug sensitivity. {yields} CD133{sup +} and CSC-like cells can be obtained from single colony forming cells of OSCCL. -- Abstract: Resistance of oral squamous cell carcinomas (OSCC) to conventional chemotherapy or radiation therapy might be due to cancer stem cells (CSCs). The development of novel anticancer drugs requires a simplemore » method for the enrichment of CSCs. CSCs can be enriched from OSCC cell lines, for example, after cultivation in serum-free cell culture medium (SFM). In our study, we analyzed four OSCC cell lines for the presence of CSCs. CSC-like cells could not be enriched with SFM. However, cell lines obtained from holoclone colonies showed CSC-like properties such as a reduced rate of cell proliferation and a reduced sensitivity to Paclitaxel in comparison to cells from the parental lineage. Moreover, these cell lines differentially expressed the CSC-marker CD133, which is also upregulated in OSCC tissues. Interestingly, CD133{sup +} cells in OSCC tissues expressed little to no Ki67, the cell proliferation marker that also indicates reduced drug sensitivity. Our study shows a method for the isolation of CSC-like cell lines from OSCC cell lines. These CSC-like cell lines could be new targets for the development of anticancer drugs under in vitro conditions.« less

Systemic approaches identify a garlic-derived chemical, Z-ajoene, as a glioblastoma multiforme cancer stem cell-specific targeting agent.

PubMed

Jung, Yuchae; Park, Heejoo; Zhao, Hui-Yuan; Jeon, Raok; Ryu, Jae-Ha; Kim, Woo-Young

2014-07-01

Glioblastoma multiforme (GBM) is one of the most common brain malignancies and has a very poor prognosis. Recent evidence suggests that the presence of cancer stem cells (CSC) in GBM and the rare CSC subpopulation that is resistant to chemotherapy may be responsible for the treatment failure and unfavorable prognosis of GBM. A garlic-derived compound, Z-ajoene, has shown a range of biological activities, including anti-proliferative effects on several cancers. Here, we demonstrated for the first time that Z-ajoene specifically inhibits the growth of the GBM CSC population. CSC sphere-forming inhibition was achieved at a concentration that did not exhibit a cytotoxic effect in regular cell culture conditions. The specificity of this inhibitory effect on the CSC population was confirmed by detecting CSC cell surface marker CD133 expression and biochemical marker ALDH activity. In addition, stem cell-related mRNA profiling and real-time PCR revealed the differential expression of CSC-specific genes, including Notch, Wnt, and Hedgehog, upon treatment with Z-ajoene. A proteomic approach, i.e., reverse-phase protein array (RPPA) and Western blot analysis, showed decreased SMAD4, p-AKT, 14.3.3 and FOXO3A expression. The protein interaction map (http://string-db.org/) of the identified molecules suggested that the AKT, ERK/p38 and TGFβ signaling pathways are key mediators of Z-ajoene's action, which affects the transcriptional network that includes FOXO3A. These biological and bioinformatic analyses collectively demonstrate that Z-ajoene is a potential candidate for the treatment of GBM by specifically targeting GBM CSCs. We also show how this systemic approach strengthens the identification of new therapeutic agents that target CSCs.

Influence of direct admission to Comprehensive Stroke Centers on the outcome of acute stroke patients treated with intravenous thrombolysis.

PubMed

Pérez de la Ossa, Natalia; Millán, Mónica; Arenillas, Juan F; Sánchez-Ojanguren, Josep; Palomeras, Ernest; Dorado, Laura; Guerrero, Cristina; Dávalos, Antoni

2009-08-01

Acute stroke patients can be transferred directly to a Comprehensive Stroke Center (CSC), where acute stroke expertise is provided 24 h a day, seven days a week, and thrombolytic treatment is administered; or they may initially receive attention at an unspecialized community hospital with secondary transfer to the CSC. Our aim is to analyze the influence of previous attention at unspecialized community hospitals on the outcome of ischemic stroke patients treated with thrombolysis. We studied 153 consecutive ischemic stroke patients treated with t-PA over a 30-month period. The primary outcome variable was functional independence at 90 days (Rankin scale, mRS

PDGFRα depletion attenuates glioblastoma stem cells features by modulation of STAT3, RB1 and multiple oncogenic signals.

PubMed

Cenciarelli, Carlo; Marei, Hany E; Felsani, Armando; Casalbore, Patrizia; Sica, Gigliola; Puglisi, Maria Ausiliatrice; Cameron, Angus J M; Olivi, Alessandro; Mangiola, Annunziato

2016-08-16

Platelet derived growth factor receptors (PDGFRs) play an important role in tumor pathogenesis, and they are frequently overexpressed in glioblastoma (GBM). Earlier we have shown a higher protein expression of PDGFR isoforms (α and β) in peritumoral-tissue derived cancer stem cells (p-CSC) than in tumor core (c-CSC) of several GBM affected patients. In the current study, in order to assess the activity of PDGFRα/PDGF-AA signaling axis, we performed time course experiments to monitor the effects of exogenous PDGF-AA on the expression of downstream target genes in c-CSC vs p-CSC. Interestingly, in p-CSC we detected the upregulation of Y705-phosphorylated Stat3, concurrent with a decrement of Rb1 protein in its active state, within minutes of PDGF-AA addition. This finding prompted us to elucidate the role of PDGFRα in self-renewal, invasion and differentiation in p-CSC by using short hairpin RNA depletion of PDGFRα expression. Notably, in PDGFRα-depleted cells, protein analysis revealed attenuation of stemness-related and glial markers expression, alongside early activation of the neuronal marker MAP2a/b that correlated with the induction of tumor suppressor Rb1. The in vitro reduction of the invasive capacity of PDGFRα-depleted CSC as compared to parental cells correlated with the downmodulation of markers of epithelial-mesenchymal transition phenotype and angiogenesis. Surprisingly, we observed the induction of anti-apoptotic proteins and compensatory oncogenic signals such as EDN1, EDNRB, PRKCB1, PDGF-C and PDGF-D. To conclude, we hypothesize that the newly discovered PDGFRα/Stat3/Rb1 regulatory axis might represent a potential therapeutic target for GBM treatment.

Regulation of HIF-1-Alpha, miR-200, and Markers of Cancer Stem Cells by CDF Under Hypoxic Condition

DTIC Science & Technology

2012-04-01

tumors. It has been well recognized that cancer stem cells (CSCs) and epithelial-to- mesenchymal transition (EMT) phenotypic cells are associated with...epithelial-to- mesenchymal transition (EMT), cancer stem cell (CSC) functions, and inflammation, which contribute to radiation therapy and chemotherapy... Hypoxia induces the VEGF and IL-6 cytokine production in PCa cells and its CSC-like sphere forming cells . ● The CSC-like sphere forming

Cottrell Scholars Collaborative New Faculty Workshop: Professional Development for New Chemistry Faculty and Initial Assessment of Its Efficacy

ERIC Educational Resources Information Center

Baker, Lane A.; Chakraverty, Devasmita; Columbus, Linda; Feig, Andrew L.; Jenks, William S.; Pilarz, Matthew; Stains, Marilyne; Waterman, Rory; Wesemann, Jodi L.

2014-01-01

The Cottrell Scholars Collaborative New Faculty Workshop (CSC NFW) is a professional development program that was initiated in 2012 to address absences in the preparation of chemistry faculty at research universities as funded researchers and educators (i.e., teacher-scholars). The primary focus of the workshop is an introduction to evidence-based…

Diverse Targets of β-Catenin during the Epithelial-Mesenchymal Transition Define Cancer Stem Cells and Predict Disease Relapse.

PubMed

Chang, Yi-Wen; Su, Ying-Jhen; Hsiao, Michael; Wei, Kuo-Chen; Lin, Wei-Hsin; Liang, Chi-Lung; Chen, Shin-Cheh; Lee, Jia-Lin

2015-08-15

Wnt signaling contributes to the reprogramming and maintenance of cancer stem cell (CSC) states that are activated by epithelial-mesenchymal transition (EMT). However, the mechanistic relationship between EMT and the Wnt pathway in CSC is not entirely clear. Chromatin immunoprecipitation with high-throughput sequencing (ChIP-seq) indicated that EMT induces a switch from the β-catenin/E-cadherin/Sox15 complex to the β-catenin/Twist1/TCF4 complex, the latter of which then binds to CSC-related gene promoters. Tandem coimmunoprecipitation and re-ChIP experiments with epithelial-type cells further revealed that Sox15 associates with the β-catenin/E-cadherin complex, which then binds to the proximal promoter region of CASP3. Through this mechanism, Twist1 cleavage is triggered to regulate a β-catenin-elicited promotion of the CSC phenotype. During EMT, we documented that Twist1 binding to β-catenin enhanced the transcriptional activity of the β-catenin/TCF4 complex, including by binding to the proximal promoter region of ABCG2, a CSC marker. In terms of clinical application, our definition of a five-gene CSC signature (nuclear β-catenin(High)/nuclear Twist1(High)/E-cadherin(Low)/Sox15(Low)/CD133(High)) may provide a useful prognostic marker for human lung cancer. ©2015 American Association for Cancer Research.

In vitro and in vivo characterization of stem-like cells from canine osteosarcoma and assessment of drug sensitivity.

PubMed

Gatti, Monica; Solari, Agnese; Pattarozzi, Alessandra; Campanella, Chiara; Thellung, Stefano; Maniscalco, Lorella; De Maria, Raffaella; Würth, Roberto; Corsaro, Alessandro; Bajetto, Adriana; Ratto, Alessandra; Ferrari, Angelo; Daga, Antonio; Barbieri, Federica; Florio, Tullio

2018-02-01

Cancer stem cell (CSC) self-renewing and drug resistance cause treatment failure and tumor recurrence. Osteosarcoma is an aggressive bone tumor characterized by biological and molecular heterogeneity, possibly dependent on CSCs. CSC identification in osteosarcoma and their efficient targeting are still open questions. Spontaneous canine osteosarcoma shares clinical and biological features with the human tumors, representing a model for translational studies. We characterized three CSC-enriched canine osteosarcoma cultures. In serum-free conditions, these CSC cultures grow as anchorage-independent spheroids, show mesenchymal-like properties and in vivo tumorigenicity, recapitulating the heterogeneity of the original osteosarcoma. Osteosarcoma CSCs express stem-related factors (Sox2, Oct4, CD133) and chemokine receptors and ligands (CXCR4, CXCL12) involved in tumor proliferation and self-renewal. Standard drugs for osteosarcoma treatment (doxorubicin and cisplatin) affected CSC-enriched and parental primary cultures, showing different efficacy within tumors. Moreover, metformin, a type-2 diabetes drug, significantly inhibits osteosarcoma CSC viability, migration and self-renewal and, in co-treatment with doxorubicin and cisplatin, enhances drug cytotoxicity. Collectively, we demonstrate that canine osteosarcoma primary cultures contain CSCs exhibiting distinctive sensitivity to anticancer agents, as a reliable experimental model to assay drug efficacy. We also provide proof-of-principle of metformin efficacy, alone or in combination, as pharmacological strategy to target osteosarcoma CSCs. Copyright © 2018 Elsevier Inc. All rights reserved.

Metabolic engineering to expand the substrate spectrum of Pseudomonas putida toward sucrose.

PubMed

Löwe, Hannes; Schmauder, Lukas; Hobmeier, Karina; Kremling, Andreas; Pflüger-Grau, Katharina

2017-08-01

Sucrose is an important disaccharide used as a substrate in many industrial applications. It is a major component of molasses, a cheap by-product of the sugar industry. Unfortunately, not all industrially relevant organisms, among them Pseudomonas putida, are capable of metabolizing sucrose. We chose a metabolic engineering approach to circumvent this blockage and equip P. putida with the activities necessary to consume sucrose. Therefore, we constructed a pair of broad-host range mini-transposons (pSST - sucrose splitting transposon), carrying either cscA, encoding an invertase able to split sucrose into glucose and fructose, or additionally cscB, encoding a sucrose permease. Introduction of cscA was sufficient to convey sucrose consumption and the additional presence of cscB had no further effect, though the sucrose permease was built and localized to the membrane. Sucrose was split extracellularly by the activity of the invertase CscA leaking out of the cell. The transposons were also used to confer sucrose consumption to Cupriavidus necator. Interestingly, in this strain, CscB acted as a glucose transporter, such that C. necator also gained the ability to grow on glucose. Thus, the pSST transposons are functional tools to extend the substrate spectrum of Gram-negative bacterial strains toward sucrose. © 2017 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.

Choroidal hemodynamic changes during isometric exercise in patients with inactive central serous chorioretinopathy.

PubMed

Tittl, Michael; Maar, Noemi; Polska, Elzbieta; Weigert, Günther; Stur, Michael; Schmetterer, Leopold

2005-12-01

Imaging studies suggest that the choroidal vasculature may be altered in central serous chorioretinopathy. Little is known, however, about the regulation of ocular blood flow in patients with central serous chorioretinopathy (CSC). The hypothesis for the present study was that choroidal blood flow changes during an increase in ocular perfusion pressure induced by isometric exercise may be altered in CSC. An observer-masked, two-cohort study was performed in 14 nonsmoking patients with chronic-relapsing but inactive CSC and in 14 healthy nonsmoking volunteers. Both groups were matched for age and sex. Subfoveal choroidal blood flow (CBF) was assessed with laser Doppler flowmetry, and ocular perfusion pressure (OPP) was calculated from mean arterial pressure (MAP) and intraocular pressure (IOP). Changes of CBF during isometric exercise over a period of 6 minutes were measured. Whereas the increase of MAP, the pulse rate, and the OPP were comparable between the two study groups, subfoveal CBF increased significantly more in the group of patients with CSC (P < 0.001). IOP remained unchanged in both groups during isometric exercise. At an 85% increase in OPP, subfoveal CBF was approximately twice as high in the patients with CSC compared with the healthy control group. The data indicate an abnormal subfoveal CBF regulation in patients with relapsing CSC compared with age-matched, nonsmoking, healthy volunteers during isometric exercise.

Topical fundus pulsation measurement in patients with active central serous chorioretinopathy.

PubMed

Tittl, Michael; Polska, Elzbieta; Kircher, Karl; Kruger, Andreas; Maar, Noemi; Stur, Michael; Schmetterer, Leopold

2003-07-01

To determine regional pulsatile choroidal blood flow using laser interferometry in patients with active central serous chorioretinopathy (CSC). The study compared an equally sized age-, sex-, and refractive error-matched control group of healthy volunteers obtained from the Department of Clinical Pharmacology with 18 consecutive patients who had newly diagnosed active, unilateral CSC obtained from the University of Vienna Eye Clinic, Vienna, Austria. Regional fundus pulsation amplitude as assessed using laser interferometry. The median age of the patients was 40 years; the male-female ratio was 16:2. Foveal fundus pulsation amplitude was significantly higher in eyes with CSC (mean [SD], 5.5 [1.7] micro m) than in the eyes of the control subjects (4.1 [1.1] micro m; P =.005). In addition, eyes with CSC had a significantly higher variability in fundus pulsation amplitude (mean [SD], 48% [20%]) assessed at different fundus locations around the leak than the controls did (20% [9%]; P<.001). To our knowledge, this is the first study that measures topical fundus pulsations in patients who have active, unilateral CSC. These data indicate a generally increased foveal pulsatile choroidal blood flow and an abnormal distribution of fundus pulsation amplitude in the area close to the leak. Whether these findings reinforce the concept that choroidal perfusion abnormalities play a role in the pathogenesis of CSC remains to be established.

Metabolic reprogramming and dependencies associated with epithelial cancer stem cells independent of the epithelial-mesenchymal transition program

PubMed Central

Aguilar, Esther; de Mas, Igor Marin; Zodda, Erika; Marin, Silvia; Morrish, Fionnuala; Selivanov, Vitaly; Meca-Cortés, Óscar; Delowar, Hossain; Pons, Mònica; Izquierdo, Inés; Celià-Terrassa, Toni; de Atauri, Pedro; Centelles, Josep J; Hockenbery, David; Thomson, Timothy M; Cascante, Marta

2016-01-01

In solid tumors, cancer stem cells (CSCs) can arise independently of epithelial-mesenchymal transition (EMT). In spite of recent efforts, the metabolic reprogramming associated with CSC phenotypes uncoupled from EMT is poorly understood. Here, by using metabolomic and fluxomic approaches, we identify major metabolic profiles that differentiate metastatic prostate epithelial CSCs (e-CSCs) from non-CSCs expressing a stable EMT. We have found that the e-CSC program in our cellular model is characterized by a high plasticity in energy substrate metabolism, including an enhanced Warburg effect, a greater carbon and energy source flexibility driven by fatty acids and amino acid metabolism and an essential reliance on the proton buffering capacity conferred by glutamine metabolism. An analysis of transcriptomic data yielded a metabolic gene signature for our e-CSCs consistent with the metabolomics and fluxomics analysis that correlated with tumor progression and metastasis in prostate cancer and in 11 additional cancer types. Interestingly, an integrated metabolomics, fluxomics and transcriptomics analysis allowed us to identify key metabolic players regulated at the post-transcriptional level, suggesting potential biomarkers and therapeutic targets to effectively forestall metastasis. PMID:27146024

Cancer stem cells: A product of clonal evolution?

PubMed

van Niekerk, Gustav; Davids, Lester M; Hattingh, Suzèl M; Engelbrecht, Anna-Mart

2017-03-01

The cancer stem cell (CSC) model has emerged as a prominent paradigm for explaining tumour heterogeneity. CSCs in tumour recurrence and drug resistance have also been implicated in a number of studies. In fact, CSCs are often identified by their expression of drug-efflux proteins which are also highly expressed in normal stem cells. Similarly, pro-survival or proliferation signalling often exhibited by stem cells is regularly reported as being upregulated by CSC. Here we review evidence suggesting that many aspects of CSCs are more readily described by clonal evolution. As an example, cancer cells often exhibit copy number gains of genes involved in drug-efflux proteins and pro-survival signalling. Consequently, clonal selection for stem cell traits may result in cancer cells developing "stemness" traits which impart a fitness advantage, without strictly following a CSC model. Finally, since symmetric cell division would give rise to more cells than asymmetric division, it is expected that more advanced tumours would depart from a CSC. Collectively, these observations suggest clonal evolution may explain many aspects of the CSC. © 2016 UICC.

Interventions for central serous chorioretinopathy: a network meta-analysis

PubMed Central

Salehi, Mahsa; Wenick, Adam S; Law, Hua Andrew; Evans, Jennifer R; Gehlbach, Peter

2016-01-01

Background Central serous chorioretinopathy (CSC) is characterized by serous detachment of the neural retina with dysfunction of the choroid and retinal pigment epithelium (RPE). The effects on the retina are usually self limited, although some people are left with irreversible vision loss due to progressive and permanent photoreceptor damage or RPE atrophy. There have been a variety of interventions used in CSC, including, but not limited to, laser treatment, photodynamic therapy (PDT), and intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) agents. However, it is not known whether these or other treatments offer significant advantages over observation or other interventions. At present there is no evidence-based consensus on the management of CSC. Due in large part to the propensity for CSC to resolve spontaneously or to follow a waxing and waning course, the most common initial approach to treatment is observation. It remains unclear whether this is the best approach with regard to safety and efficacy. Objectives To compare the relative effectiveness of interventions for central serous chorioretinopathy. Search methods We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (2015, Issue 9), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to February 2014), EMBASE (January 1980 to October 2015), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 5 October 2015. Selection criteria Randomized controlled trials (RCTs) that compared any intervention for CSC with any other intervention for CSC or control. Data collection and analysis Two review authors independently selected studies and extracted data. We pooled data from all studies using a fixed-effect model. For interventions applied to the eye (i.e. not systemic interventions), we synthesized direct and indirect evidence in a network meta-analysis model. Main results We included 25 studies with 1098 participants (1098 eyes) and follow-up from 16 weeks to 12 years. Studies were conducted in Europe, North and South America, Middle East, and Asia. The trials were small (most trials enrolled fewer than 50 participants) and poorly reported; often it was unclear whether key aspects of the trial, such as allocation concealment, had been done. A substantial proportion of the trials were not masked. The studies considered a variety of treatments: anti-VEGF (ranibizumab, bevacizumab), PDT (full-dose, half-dose, 30%, low-fluence), laser treatment (argon, krypton and micropulse laser), beta-blockers, carbonic anhydrase inhibitors, Helicobactor pylori treatment, and nutritional supplements (Icaps, lutein); there were only one or two trials contributing data for each comparison. We downgraded for risk of bias and imprecision for most analyses, reflecting study limitations and imprecise estimates. Network meta-analysis (as planned in our protocol) did not help to resolve this uncertainty due to a lack of trials, and problems with intransitivity, particularly with respect to acute or chronic CSC. Low quality evidence from two trials suggested little difference in the effect of anti-VEGF (ranibizumab or bevacizumab) or observation on change in visual acuity at six months in acute CSC (mean difference (MD) 0.01 LogMAR (logarithm of the minimal angle of resolution), 95% confidence interval (CI) −0.02 to 0.03; 64 participants). CSC had resolved in all participants by six months. There were no significant adverse effects noted. Low quality evidence from one study (58 participants) suggested that half-dose PDT treatment of acute CSC probably results in a small improvement in vision (MD −0.10 logMAR, 95% CI −0.18 to −0.02), less recurrence (risk ratio (RR) 0.10, 95% CI 0.01 to 0.81) and less persistent CSC (RR 0.12, 95% CI 0.01 to 1.02) at 12 months compared to sham treatment. There were no significant adverse events noted. Low quality evidence from two trials (56 participants) comparing anti-VEGF to low-fluence PDT in chronic CSC found little evidence for any difference in visual acuity at 12 months (MD 0.03 logMAR, 95% CI −0.08 to 0.15). There was some evidence that more people in the anti-VEGF group had recurrent CSC compared to people treated with PDT but, due to inconsistency between trials, it was difficult to estimate an effect. More people in the anti-VEGF group had persistent CSC at 12 months (RR 6.19, 95% CI 1.61 to 23.81; 34 participants). Two small trials of micropulse laser, one in people with acute CSC and one in people with chronic CSC, provided low quality evidence that laser treatment may lead to better visual acuity (MD −0.20 logMAR, 95% CI −0.30 to −0.11; 45 participants). There were no significant adverse effects noted. Other comparisons were largely inconclusive. We identified 12 ongoing trials covering the following interventions: aflibercept and eplerenone in acute CSC; spironolactone, eplerenone, lutein, PDT, and micropulse laser in chronic CSC; and micropulse laser and oral mifepristone in two trials where type of CSC not clearly specified. Authors’ conclusions CSC remains an enigmatic condition in large part due to a natural history of spontaneous improvement in a high proportion of people and also because no single treatment has provided overwhelming evidence of efficacy in published RCTs. While a number of interventions have been proposed as potentially efficacious, the quality of study design, execution of the study and the relatively small number of participants enrolled and followed to revealing endpoints limits the utility of existing data. It is not clear whether there is a clinically important benefit to treating acute CSC which often resolves spontaneously as part of its natural history. RCTs comparing individual treatments to the natural history would be valuable in identifying potential treatment groups for head-to-head comparison. Of the interventions studied to date, PDT or micropulse laser treatment appear the most promising for study in future trials. PMID:26691378

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

Ding, Laura; Harvey, Stephen P.; Teeter, Glenn

We demonstrate the potential of X-ray photoelectron spectroscopy (XPS) to characterize new carrier-selective contacts (CSC) for solar cell application. We show that XPS not only provides information about the surface chemical properties of the CSC material, but that operando XPS, i.e. under light bias condition, can also directly measure the photovoltage that develops at the CSC/absorber interface, revealing device relevant information without the need of assembling a full solar cell. We present the application of the technique to molybdenum oxide hole-selective contact films on a crystalline silicon absorber.

Batch Conversion of 1-D FITS Spectra to Common Graphical Display Files

NASA Astrophysics Data System (ADS)

MacConnell, Darrell J.; Patterson, A. P.; Wing, R. F.; Costa, E.; Jedrzejewski, R. I.

2008-09-01

Authors DJM, RFW, and EC have accumulated about 1000 spectra of cool stars from CTIO, ESO, and LCO over the interval 1985 to 1994 and processed them with the standard IRAF tasks into FITS files of normalized intensity vs. wavelength. With the growth of the Web as a means of exchanging and preserving scientific information, we desired to put the spectra into a Web-readable format. We have searched without success sites such as the Goddard FITS Image Viewer page, http://fits.gsfc.nasa.gov/fits_viewer.html, for a program to convert a large number of 1-d stellar spectra from FITS format into common formats such as PDF, PS, or PNG. Author APP has written a Python script to do this using the PyFITS module and plotting routines from Pylab. The program determines the wavelength calibration using header keywords and creates PNG plots with a legend read from a CSV file that may contain the star name, position, spectral type, etc. It could readily be adapted to perform almost any kind of simple batch processing of astronomical data. The program may be obtained from the first author (jack@stsci.edu). Support for DJM from the research program for CSC astronomers at STScI is gratefully acknowledged. The Space Telescope Science Institute is operated by the Association of Universities for Research in Astronomy Inc. under NASA contract NAS 5-26555.

СD44+/CD24- markers of cancer stem cells in patients with breast cancer of different molecular subtypes.

PubMed

Chekhun, S V; Zadvorny, T V; Tymovska, Yu O; Anikusko, M F; Novak, O E; Polishchuk, L Z

2015-03-01

To determine frequency of tumors with immunohistochemical markers of cancer stem cells (CSC) CD44+/CD24- in patients with breast cancer (BC) of different molecular subtype and to evaluate their prognostic value. Surgical material of 132 patients with BC stage I-II, age from 23 to 75 years, mean age - 50.2 ± 3.1 years was studied. Clinical, immunohistochemical (expression CD44+/CD24-), morphological, statistical. BC is characterized by heterogeneity of molecular subtypes and expression of markers (CD44+/CD24-). Immunohistochemical study of expression of CSC markers in surgical material has detected their expression in 34 (25.4%) patients with BC of different molecular subtypes. The highest frequency of cells with expression of CSC marker was observed in patients with basal molecular subtype (44.8% patients). Most of BC patients with phenotype CD44+/CD24 had stage I of tumor process (34.3%). Statistical processing of data has showen that Yule colligation coefficient equaled 0.28 (р > 0.05) that argues poor correlation between stage of tumor process and number of tumors with positive expression of CSC markers. Statistical processing of data has showen high correlation between presence of cells with expression of CSC markers and metastases of BC in regional lymph nodes (Yule colligation coefficient equals 0.943; р < 0.5). Difference in overall survival of patients with BC of basal molecular subtype depending on expression of CSC CD44+/CD24- markers was detected. Survival of patients with basal BC was reliably higher at lack in tumors of cells with CSC markers CD44+/CD24- and, correspondingly, lower at presence of such cells (р < 0.05). In patients with BC of luminal (A and B), HER-2-positive subtypes, significant change in survival of patients depending on expression of CSC markers was not determined (р > 0.05). Significance of tumor cells with markers CD44+/CD24- within the limits of molecular subtype of BC may be additional criterion for advanced biological characteristic of BC, and in patients with BC of basal molecular subtype - for predictive evaluation of individual potential of tumor to aggressive clinical course.

The IDEAS**2 computing environment

NASA Technical Reports Server (NTRS)

Racheli, Ugo

1990-01-01

This document presents block diagrams of the IDEAS**2 computing environment. IDEAS**2 is the computing environment selected for system engineering (design and analysis) by the Center for Space Construction (CSC) at the University of Colorado (UCB). It is intended to support integration and analysis of any engineering system and at any level of development, from Pre-Phase A conceptual studies to fully mature Phase C/D projects. The University of Colorado (through the Center for Space Construction) has joined the Structural Dynamics Research Corporation (SDRC) University Consortium which makes available unlimited software licenses for instructional purposes. In addition to providing the backbone for the implementation of the IDEAS**2 computing environment, I-DEAS can be used as a stand-alone product for undergraduate CAD/CAE instruction. Presently, SDRC is in the process of releasing I-DEAS level 5.0 which represents a substantial improvement in both the user interface and graphic processing capabilities. IDEAS**2 will be immediately useful for a number of current programs within CSC (such as DYCAM and the 'interruptability problem'). In the future, the following expansions of the basic IDEAS**2 program will be pursued, consistent with the overall objectives of the Center and of the College: upgrade I-DEAS and IDEAS**2 to level 5.0; create new analytical programs for applications not limited to orbital platforms; research the semantic organization of engineering databases; and create an 'interoperability' testbed.

Chitin based heteroatom-doped porous carbon as electrode materials for supercapacitors.

PubMed

Zhou, Jie; Bao, Li; Wu, Shengji; Yang, Wei; Wang, Hui

2017-10-01

Chitin biomass has received much attention as an amino-functional polysaccharide precursor for synthesis of carbon materials. Rich nitrogen and oxygen dual-doped porous carbon derived from cicada slough (CS), a renewable biomass mainly composed of chitin, was synthesized and employed as electrode materials for electrochemical capacitors, for the first time ever. The cicada slough-derived carbon (CSC) was prepared by a facile process via pre-carbonization in air, followed by KOH activation. The weight ratio of KOH and char plays an important role in fabricating the microporous structure and tuning the surface chemistry of CSC. The obtained CSC had a large specific surface area (1243-2217m 2 g -1 ), fairly high oxygen content (28.95-33.78 at%) and moderate nitrogen content (1.47-4.35 at%). The electrochemical performance of the CS char and CSC as electrodes for capacitors was evaluated in a three-electrode cell configuration with 6M KOH as the electrolyte. Electrochemical studies showed that the as-prepared CSC activated at the KOH-to-char weight ratio of 2 exhibited the highest specific capacitance (266.5Fg -1 at a current density of 0.5Ag -1 ) and excellent rate capability (196.2Fg -1 remained at 20Ag -1 ) and cycle durability. In addition, the CSC-2-based symmetrical device possessed the desirable energy density and power density of about 15.97Whkg -1 and 5000Wkg -1 at 5Ag -1 , respectively. Copyright © 2017 Elsevier Ltd. All rights reserved.

Clinically significant changes in the emotional condition of relatives of patients with severe traumatic brain injury during sub-acute rehabilitation.

PubMed

Norup, Anne; Kristensen, Karin Spangsberg; Poulsen, Ingrid; Nielsen, Christina Löfvquist; Mortensen, Erik Lykke

2013-09-01

To investigate clinically significant change in the emotional condition of relatives of patients with severe traumatic brain injury during sub-acute rehabilitation. Participants were 62 pairs of relatives and patients. Relatives completed the anxiety and depression scales from the Symptom Checklist-90-R (SCL-90-R) when the patients were admitted to sub-acute rehabilitation and at discharge. Improvement in emotional condition was investigated using the following criteria: (i) statistically reliable improvement; and (ii) clinically significant change (CSC). At admission, 53.2% and 58.1% of relatives had scores above cut-off values on the anxiety and depression scales, respectively. On the anxiety scale 69.7% of these experienced a reliable improvement according to the Reliable Change Index (RCI) and 45.5% also obtained CSC, as their end-point was below the cut-off value. On the depression scale the corresponding figures were 44.4% and 41.7%, respectively. When comparing relatives with and without CSC, we found that CSC in symptoms of anxiety was associated with significantly better functional improvement during rehabilitation and a shorter period of post-traumatic amnesia in the patients. Of the relatives who reported scores above cut-off values on the anxiety and depression scales at patient's admission, approximately 40% experienced CSC in anxiety and depression during the patient's rehabilitation. Relatives of patients experiencing improvement during inpatient rehabilitation are more likely to experience CSC in anxiety.

What Tumor Dynamics Modeling Can Teach us About Exploiting the Stem-Cell View for Better Cancer Treatment

PubMed Central

Day, Roger S

2015-01-01

The cancer stem cell hypothesis is that in human solid cancers, only a small proportion of the cells, the cancer stem cells (CSCs), are self-renewing; the vast majority of the cancer cells are unable to sustain tumor growth indefinitely on their own. In recent years, discoveries have led to the concentration, if not isolation, of putative CSCs. The evidence has mounted that CSCs do exist and are important. This knowledge may promote better understanding of treatment resistance, create opportunities to test agents against CSCs, and open up promise for a fresh approach to cancer treatment. The first clinical trials of new anti-CSC agents are completed, and many others follow. Excitement is mounting that this knowledge will lead to major improvements, even breakthroughs, in treating cancer. However, exploitation of this phenomenon may be more successful if informed by insights into the population dynamics of tumor development. We revive some ideas in tumor dynamics modeling to extract some guidance in designing anti-CSC treatment regimens and the clinical trials that test them. PMID:25780337

The Art and Science of Defense Logistics

DTIC Science & Technology

1995-04-01

The Art And Science Of Defense Logistics CSC 1995 SUBJECT AREA - Logistics THE ART AND SCIENCE OF DEFENSE LOGISTICS...Government EXECUTIVE SUMMARY Title: The Art and Science of Defense Logistics Author: Major S. I. Schuler, USMC Research Questions: 1...00-1995 4. TITLE AND SUBTITLE The Art And Science Of Defense Logistics 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6

Fast Constrained Spectral Clustering and Cluster Ensemble with Random Projection

PubMed Central

Liu, Wenfen

2017-01-01

Constrained spectral clustering (CSC) method can greatly improve the clustering accuracy with the incorporation of constraint information into spectral clustering and thus has been paid academic attention widely. In this paper, we propose a fast CSC algorithm via encoding landmark-based graph construction into a new CSC model and applying random sampling to decrease the data size after spectral embedding. Compared with the original model, the new algorithm has the similar results with the increase of its model size asymptotically; compared with the most efficient CSC algorithm known, the new algorithm runs faster and has a wider range of suitable data sets. Meanwhile, a scalable semisupervised cluster ensemble algorithm is also proposed via the combination of our fast CSC algorithm and dimensionality reduction with random projection in the process of spectral ensemble clustering. We demonstrate by presenting theoretical analysis and empirical results that the new cluster ensemble algorithm has advantages in terms of efficiency and effectiveness. Furthermore, the approximate preservation of random projection in clustering accuracy proved in the stage of consensus clustering is also suitable for the weighted k-means clustering and thus gives the theoretical guarantee to this special kind of k-means clustering where each point has its corresponding weight. PMID:29312447

DEspR roles in tumor vasculo-angiogenesis, invasiveness, CSC-survival and anoikis resistance: a 'common receptor coordinator' paradigm.

PubMed

Herrera, Victoria L; Decano, Julius L; Tan, Glaiza A; Moran, Ann M; Pasion, Khristine A; Matsubara, Yuichi; Ruiz-Opazo, Nelson

2014-01-01

A priori, a common receptor induced in tumor microvessels, cancer cells and cancer stem-like cells (CSCs) that is involved in tumor angiogenesis, invasiveness, and CSC anoikis resistance and survival, could underlie contemporaneous coordination of these events rather than assume stochasticity. Here we show that functional analysis of the dual endothelin1/VEGFsignal peptide receptor, DEspR, (formerly named Dear, Chr.4q31.2) supports the putative common receptor paradigm in pancreatic ductal adenocarcinoma (PDAC) and glioblastoma (GBM) selected for their invasiveness, CD133+CSCs, and polar angiogenic features. Unlike normal tissue, DEspR is detected in PDAC and GBM microvessels, tumor cells, and CSCs isolated from PDAC-Panc1 and GBM-U87 cells. DEspR-inhibition decreased angiogenesis, invasiveness, CSC-survival and anoikis resistance in vitro, and decreased Panc1-CSC and U87-CSC xenograft tumor growth, vasculo-angiogenesis and invasiveness in nude(nu/nu) rats, suggesting that DEspR activation would coordinate these tumor progression events. As an accessible, cell-surface 'common receptor coordinator', DEspR-inhibition defines a novel targeted-therapy paradigm for pancreatic cancer and glioblastoma.

DEspR Roles in Tumor Vasculo-Angiogenesis, Invasiveness, CSC-Survival and Anoikis Resistance: A ‘Common Receptor Coordinator’ Paradigm

PubMed Central

Herrera, Victoria L.; Decano, Julius L.; Tan, Glaiza A.; Moran, Ann M.; Pasion, Khristine A.; Matsubara, Yuichi; Ruiz-Opazo, Nelson

2014-01-01

A priori, a common receptor induced in tumor microvessels, cancer cells and cancer stem-like cells (CSCs) that is involved in tumor angiogenesis, invasiveness, and CSC anoikis resistance and survival, could underlie contemporaneous coordination of these events rather than assume stochasticity. Here we show that functional analysis of the dual endothelin1/VEGFsignal peptide receptor, DEspR, (formerly named Dear, Chr.4q31.2) supports the putative common receptor paradigm in pancreatic ductal adenocarcinoma (PDAC) and glioblastoma (GBM) selected for their invasiveness, CD133+CSCs, and polar angiogenic features. Unlike normal tissue, DEspR is detected in PDAC and GBM microvessels, tumor cells, and CSCs isolated from PDAC-Panc1 and GBM-U87 cells. DEspR-inhibition decreased angiogenesis, invasiveness, CSC-survival and anoikis resistance in vitro, and decreased Panc1-CSC and U87-CSC xenograft tumor growth, vasculo-angiogenesis and invasiveness in nudenu/nu rats, suggesting that DEspR activation would coordinate these tumor progression events. As an accessible, cell-surface ‘common receptor coordinator’, DEspR-inhibition defines a novel targeted-therapy paradigm for pancreatic cancer and glioblastoma. PMID:24465725

Chitosan promotes cancer progression and stem cell properties in association with Wnt signaling in colon and hepatocellular carcinoma cells

PubMed Central

Chang, Po-Hsiang; Sekine, Keisuke; Chao, Hsiao-Mei; Hsu, Shan-hui; Chern, Edward

2017-01-01

Cancer stem cells (CSCs), a small population of cancer cells, have been considered to be the origin of cancer initiation, recurrence, and metastasis. Tumor microenvironment provides crucial signals for CSCs to maintain stem cell properties and promotes tumorigenesis. Therefore, establishment of an appropriate cell culture system to mimic the microenvironment for CSC studies is an important issue. In this study, we grew colon and hepatocellular carcinoma (HCC) cells on chitosan membranes and evaluated the tumor progression and the CSC properties. Experimental results showed that culturing cancer cells on chitosan increased cell motility, drug resistance, quiescent population, self-renewal capacity, and the expression levels of stemness and CSC marker genes, such as OCT4, NANOG, CD133, CD44, and EpCAM. Furthermore, we demonstrated that chitosan might activate canonical Wnt/β-catenin-CD44 axis signaling in CD44positive colon cancer cells and noncanonical Wnt-STAT3 signaling in CD44negative HCC cells. In conclusion, chitosan as culture substrates activated the essential signaling of CSCs and promoted CSC properties. The chitosan culture system provides a convenient platform for the research of CSC biology and screening of anticancer drugs. PMID:28367998

Faculty Development for the 21st Century

ERIC Educational Resources Information Center

Diaz, Veronica; Garrett, P. B.; Kinley, Edward R.; Moore, John F.; Schwartz, Celeste M.; Kohrman, Pat

2009-01-01

In the 21st century, colleges and universities need to consider faculty development programs in the same way that they view academic programs for their Net Gen and Millennial students. In other words, successful faculty development programs should include mentoring, delivery in a variety of on-campus and off-campus formats (face-to-face, blended,…

(Z)-3,5,4'-Trimethoxystilbene Limits Hepatitis C and Cancer Pathophysiology by Blocking Microtubule Dynamics and Cell Cycle Progression

PubMed Central

Nguyen, Charles B.; Kotturi, Hari; Waris, Gulam; Mohammed, Altaf; Chandrakesan, Parthasarathy; May, Randal; Sureban, Sripathi; Weygant, Nathaniel; Qu, Dongfeng; Rao, Chinthalapally V.; Dhanasekaran, Danny N.; Bronze, Michael S.; Houchen, Courtney W.; Ali, Naushad

2016-01-01

Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related deaths worldwide. Chronic hepatitis C virus (HCV) infection causes induction of several tumor/cancer stem cell (CSC) markers and is known to be a major risk factor for development of HCC. Therefore, drugs that simultaneously target viral replication and CSC properties are needed for a risk-free treatment of advanced stage liver diseases including HCC. Here, we demonstrated that (Z)-3,5,4’-trimethoxystilbene (Z-TMS) exhibits potent anti-tumor and anti-HCV activities without exhibiting cytotoxicity to human hepatocytes in vitro or in mice livers. Diethylnitrosamine (DEN)/carbon tetrachloride (CCl4) extensively induced expression of DCLK1 (a CSC marker) in the livers of C57BL/6 mice following hepatic injury. Z-TMS exhibited hepatoprotective effects against DEN/CCl4-induced injury by reducing DCLK1 expression and improving histological outcomes. The drug caused bundling of DCLK1 with microtubules and blocked cell cycle progression at G2/M phase in hepatoma cells via downregulation of CDK1, induction of p21cip1/waf1 expression, and inhibition of Akt (Ser473) phosphorylation. Z-TMS also inhibited proliferation of erlotinib-resistant lung adenocarcinoma cells (H1975) bearing the T790M EGFR mutation most likely by promoting autophagy and nuclear fragmentation. In conclusion, Z-TMS appears to be a unique therapeutic agent targeting HCV and concurrently eliminating cells with neoplastic potential during chronic liver diseases including HCC. It may also be a valuable drug for targeting drug-resistant carcinomas and cancers of the lungs, pancreas, colon, and intestine in which DCLK1 is involved in tumorigenesis. PMID:27287718

The Department of the Interior Southeast Climate Science Center synthesis report 2011–15—Projects, products, and science priorities

USGS Publications Warehouse

Varela Minder, Elda; Lascurain, Aranzazu R.; McMahon, Gerard

2016-09-28

IntroductionIn 2009, the U.S. Department of the Interior (DOI) Secretary Ken Salazar established a network of eight regional Climate Science Centers (CSCs) that, along with the Landscape Conservation Cooperatives (LCCs), would help define and implement the Department's climate adaptation response. The Southeast Climate Science Center (SE CSC) was established at North Carolina State University (NCSU) in Raleigh, North Carolina, in 2010, under a 5-year cooperative agreement with the U.S. Geological Survey (USGS), to identify and address the regional challenges presented by climate change and variability in the Southeastern United States. All eight regional CSC hosts, including NCSU, were selected through a competitive process.Since its opening, the focus of the SE CSC has been on working with partners in the identification and development of research-based information that can assist managers, including cultural and natural resource managers, in adapting to global change processes, such as climate and land use change, that operate at local to global scales and affect resources important to the DOI mission. The SE CSC was organized to accomplish three goals:Provide co-produced, researched based, actionable science that supports transparent global change adaptation decisions.Convene conversations among decision makers, scientists, and managers to identify key ecosystem adaptation decisions driven by climate and land use change, the values and objectives that will be used to make decisions, and the research-based information needed to assess adaptation options.Build the capacity of natural resource professionals, university faculty, and students to understand and frame natural resource adaptation decisions and develop and use research-based information to make adaptation decisions.This report provides an overview of the SE CSC and the projects developed by the SE CSC since its inception. An important goal of this report is to provide a framework for understanding the evolution of the SE CSC science agenda, which has evolved over the first 5 years of the Center’s operation.

Optimum 3D Matrix Stiffness for Maintenance of Cancer Stem Cells Is Dependent on Tissue Origin of Cancer Cells

PubMed Central

Jabbari, Esmaiel; Sarvestani, Samaneh K.; Daneshian, Leily; Moeinzadeh, Seyedsina

2015-01-01

Introduction The growth and expression of cancer stem cells (CSCs) depend on many factors in the tumor microenvironment. The objective of this work was to investigate the effect of cancer cells’ tissue origin on the optimum matrix stiffness for CSC growth and marker expression in a model polyethylene glycol diacrylate (PEGDA) hydrogel without the interference of other factors in the microenvironment. Methods Human MCF7 and MDA-MB-231 breast carcinoma, HCT116 colorectal and AGS gastric carcinoma, and U2OS osteosarcoma cells were used. The cells were encapsulated in PEGDA gels with compressive moduli in the 2-70 kPa range and optimized cell seeding density of 0.6x106 cells/mL. Micropatterning was used to optimize the growth of encapsulated cells with respect to average tumorsphere size. The CSC sub-population of the encapsulated cells was characterized by cell number, tumorsphere size and number density, and mRNA expression of CSC markers. Results The optimum matrix stiffness for growth and marker expression of CSC sub-population of cancer cells was 5 kPa for breast MCF7 and MDA231, 25 kPa for colorectal HCT116 and gastric AGS, and 50 kPa for bone U2OS cells. Conjugation of a CD44 binding peptide to the gel stopped tumorsphere formation by cancer cells from different tissue origin. The expression of YAP/TAZ transcription factors by the encapsulated cancer cells was highest at the optimum stiffness indicating a link between the Hippo transducers and CSC growth. The optimum average tumorsphere size for CSC growth and marker expression was 50 μm. Conclusion The marker expression results suggest that the CSC sub-population of cancer cells resides within a niche with optimum stiffness which depends on the cancer cells’ tissue origin. PMID:26168187

The effect of canaloplasty with suprachoroidal drainage combined with cataract surgery - 1-year results.

PubMed

Seuthe, Anna-Maria; Januschowski, Kai; Mariacher, Siegfried; Ebner, Martina; Opitz, Natalia; Szurman, Peter; Boden, Karl

2018-02-01

The purpose of this study was to investigate the safety and efficacy of phacocanaloplasty with suprachoroidal drainage (PCscD) and to compare its intraocular pressure (IOP)-lowering and drug-sparing effect to canaloplasty with suprachoroidal drainage (CscD). The study retrospective interventional study included patients with open-angle glaucoma or secondary forms of glaucoma who underwent either CscD or PCscD between the year 2011 and 2014 in Knappschaft Eye Clinic Sulzbach. Primary end-points were IOP reduction and the number of IOP-lowering medication after 12 months. Secondary end-points were intraoperative and postoperative complications. A total of 328 eyes were included, 193 were treated with CscD and 135 underwent PCscD. Canaloplasty with scD achieved an IOP reduction of 37.0% (from 20.9 ± 3.6 mmHg to 13.2 ± 2.6 mmHg) after 1 year, whereas PCscD showed a significant higher reduction of 47.4% (from 23.2 ± 5.1 mmHg to 12.2 ± 1.7 mmHg). Reduction in IOP-lowering medication was higher after PCscD (from 3.6 ± 0.6 to 0.2 ± 0.5) than after CscD (from 3.5 ± 0.8 to 0.7 ± 1.0). Twelve months after surgery 55.5% in the CscD group and 80.2% in the PCscD group were free of IOP-lowering medication. In both groups, no severe or sight-threatening complications occurred. Combining cataract surgery and CscD achieves a higher IOP reduction, and patients postoperatively need less IOP-lowering medication than after CscD alone. © 2017 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

The global burden of cataract.

PubMed

Rao, Gullapalli N; Khanna, Rohit; Payal, Abhishek

2011-01-01

To review the previous year's literature related to prevalence of blindness in general, blindness due to cataract, cataract surgical coverage (CSC) and cataract surgical rates (CSRs). Cataracts are the major cause of blindness and visual impairment in developing countries and contributes to more than 90% of the total disability adjusted life years. This review shows that coverage continues to be a problem in many countries, especially for the female population, those residing in rural areas and those who are illiterate. Although CSR is an indicator of the availability and acceptability of services, for measuring the impact of the program, we should look at combining CSR with CSC. This strategy would also enable us achieve our goal of eliminating avoidable blindness due to cataracts by the year 2020. Cataracts still continue- to be a major cause of blindness globally and with the rapidly aging population, it is a challenge to tackle. We need to plan a comprehensive strategy addressing issues related to availability, affordability, accessibility and acceptability of eye-care services.

Factors Influencing Success of Conditionally Admitted Students in Graduate TESOL Programs

ERIC Educational Resources Information Center

Micek, Timothy A.; Kim, Soonhyang; Weinstein, Daniel A.

2012-01-01

Many graduate TESOL programs grapple with whether to admit applicants who fall short of meeting established admission criteria yet who show promise as future TESOL professionals. This study examined key characteristics affecting the success of candidates admitted conditionally to graduate TESOL programs. Participants were 21 students who had been…

Success by Eight: A Program for 21st Century Schools.

ERIC Educational Resources Information Center

Domenech, Daniel A.

1999-01-01

The Fairfax County (Virginia) Schools have developed a pilot program, Success by Eight, that groups students ages 5 to 8 for different types of learning, based on performance in each subject. By restructuring K-2 classes into multiple, flexible groups, the program provides opportunities for continuous learning and development during critical…

Calcium silicate-based cements: composition, properties, and clinical applications.

PubMed

Dawood, Alaa E; Parashos, Peter; Wong, Rebecca H K; Reynolds, Eric C; Manton, David J

2017-05-01

Mineral trioxide aggregate (MTA) is a calcium silicate-based cement (CSC) commonly used in endodontic procedures involving pulpal regeneration and hard tissue repair, such as pulp capping, pulpotomy, apexogenesis, apexification, perforation repair, and root-end filling. Despite the superior laboratory and clinical performance of MTA in comparison with previous endodontic repair cements, such as Ca(OH) 2 , MTA has poor handling properties and a long setting time. New CSC have been commercially launched and marketed to overcome the limitations of MTA. The aim of the present review was to explore the available literature on new CSC products, and to give evidence-based recommendations for the clinical use of these materials. Within the limitations of the available data in the literature regarding the properties and performance of the new CSC, the newer products could be promising alternatives to MTA; however, further research is required to support this assumption. © 2015 Wiley Publishing Asia Pty Ltd.

Maintenance of Mitochondrial Oxygen Homeostasis by Cosubstrate Compensation

PubMed Central

Kueh, Hao Yuan; Niethammer, Philipp; Mitchison, Timothy J.

2013-01-01

Mitochondria maintain a constant rate of aerobic respiration over a wide range of oxygen levels. However, the control strategies underlying oxygen homeostasis are still unclear. Using mathematical modeling, we found that the mitochondrial electron transport chain (ETC) responds to oxygen level changes by undergoing compensatory changes in reduced electron carrier levels. This emergent behavior, which we named cosubstrate compensation (CSC), enables the ETC to maintain homeostasis over a wide of oxygen levels. When performing CSC, our ETC models recapitulated a classic scaling relationship discovered by Chance [Chance B (1965) J. Gen. Physiol. 49:163-165] relating the extent of oxygen homeostasis to the kinetics of mitochondrial electron transport. Analysis of an in silico mitochondrial respiratory system further showed evidence that CSC constitutes the dominant control strategy for mitochondrial oxygen homeostasis during active respiration. Our findings indicate that CSC constitutes a robust control strategy for homeostasis and adaptation in cellular biochemical networks. PMID:23528093

Delivery of therapeutics using nanocarriers for targeting cancer cells and cancer stem cells.

PubMed

Krishnamurthy, Sangeetha; Ke, Xiyu; Yang, Yi Yan

2015-01-01

Development of cancer resistance, cancer relapse and metastasis are attributed to the presence of cancer stem cells (CSCs). Eradication of this subpopulation has been shown to increase life expectancy of patients. Since the discovery of CSCs a decade ago, several strategies have been devised to specifically target them but with limited success. Nanocarriers have recently been employed to deliver anti-CSC therapeutics for reducing the population of CSCs at the tumor site with great success. This review discusses the different therapeutic strategies that have been employed using nanocarriers, their advantages, success in targeting CSCs and the challenges that are to be overcome. Exploiting this new modality of cancer treatment in the coming decade may improve outcomes profoundly with promise of effective treatment response and reducing relapse and metastasis.

Cigarette smoke condensate inhibits collagen gel contraction and prostaglandin E2 production in human gingival fibroblasts.

PubMed

Romero, A; Cáceres, M; Arancibia, R; Silva, D; Couve, E; Martínez, C; Martínez, J; Smith, P C

2015-06-01

Granulation tissue remodeling and myofibroblastic differentiation are critically important events during wound healing. Tobacco smoking has a detrimental effect in gingival tissue repair. However, studies evaluating the effects of cigarette smoke on these events are lacking. We used gingival fibroblasts cultured within free-floating and restrained collagen gels to simulate the initial and final steps of the granulation tissue phase during tissue repair. Collagen gel contraction was stimulated with serum or transforming growth factor-β1. Cigarette smoke condensate (CSC) was used to evaluate the effects of tobacco smoke on gel contraction. Protein levels of alpha-smooth muscle actin, β1 integrin, matrix metalloproteinase-3 and connective tissue growth factor were evaluated through Western blot. Prostaglandin E(2) (PGE(2)) levels were determined through ELISA. Actin organization was evaluated through confocal microscopy. CSC reduced collagen gel contraction induced by serum and transforming growth factor-β1 in restrained collagen gels. CSC also altered the development of actin stress fibers in fibroblasts cultured within restrained collagen gels. PGE(2) levels were strongly diminished by CSC in three-dimensional cell cultures. However, other proteins involved in granulation tissue remodeling and myofibroblastic differentiation such as alpha-smooth muscle actin, β1 integrin, matrix metalloproteinase-3 and connective tissue growth factor, were unmodified by CSC. CSC may alter the capacity of gingival fibroblasts to remodel and contract a collagen matrix. Inhibition of PGE(2) production and alterations of actin stress fibers in these cells may impair proper tissue maturation during wound healing in smokers. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Optical quality in central serous chorioretinopathy.

PubMed

Lee, Kyungmin; Sohn, Joonhong; Choi, Jong Gil; Chung, Sung Kun

2014-12-02

To assess optical quality and intraocular scattering using the Optical Quality Analysis System (OQAS) in central serous chorioretinopathy (CSC) and to determine the effects of retinal changes on optical quality. This was a prospective, case-control study. Participants were 29 patients with diagnosis of CSC. The control group consisted of the patients' unaffected eyes. Initial logMAR visual acuity, central macular thickness (by spectral domain optical coherence tomography), and optical quality parameters including modulation transfer function (MTF) cutoff frequency, Strehl (2-dimensional) ratio, and OQAS values at 100%, 20%, and 9% contrast levels were investigated. Objective scattering index (OSI) at 4.0-mm pupil size was assessed in both eyes by using the OQAS. After 3 months of treatment, which included observation and focal laser or injections of antivascular endothelial growth factor, every CSC-affected eye was followed. Main outcome measures were differences between clinical parameters of the CSC-affected eye and those of the control eye and changes in those parameters according to the clinical course of CSC over 3 months. In CSC-affected eyes, the MTF cutoff was significantly reduced (P = 0.01), and OSI was significantly increased (P = 0.03). As macular thickness decreased, OSI decreased but did not become normalized compared to the control eye, nor was it statistically significantly correlated with central macular thickness change. Retinal change affected optical quality and intraocular scatter. Therefore, when the severity of a cataract is assessed using the OQAS, retinal status should be considered when interpreting OQAS values. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

Structural analyses of the CRISPR protein Csc2 reveal the RNA-binding interface of the type I-D Cas7 family.

PubMed

Hrle, Ajla; Maier, Lisa-Katharina; Sharma, Kundan; Ebert, Judith; Basquin, Claire; Urlaub, Henning; Marchfelder, Anita; Conti, Elena

2014-01-01

Upon pathogen invasion, bacteria and archaea activate an RNA-interference-like mechanism termed CRISPR (clustered regularly interspaced short palindromic repeats). A large family of Cas (CRISPR-associated) proteins mediates the different stages of this sophisticated immune response. Bioinformatic studies have classified the Cas proteins into families, according to their sequences and respective functions. These range from the insertion of the foreign genetic elements into the host genome to the activation of the interference machinery as well as target degradation upon attack. Cas7 family proteins are central to the type I and type III interference machineries as they constitute the backbone of the large interference complexes. Here we report the crystal structure of Thermofilum pendens Csc2, a Cas7 family protein of type I-D. We found that Csc2 forms a core RRM-like domain, flanked by three peripheral insertion domains: a lid domain, a Zinc-binding domain and a helical domain. Comparison with other Cas7 family proteins reveals a set of similar structural features both in the core and in the peripheral domains, despite the absence of significant sequence similarity. T. pendens Csc2 binds single-stranded RNA in vitro in a sequence-independent manner. Using a crosslinking - mass-spectrometry approach, we mapped the RNA-binding surface to a positively charged surface patch on T. pendens Csc2. Thus our analysis of the key structural and functional features of T. pendens Csc2 highlights recurring themes and evolutionary relationships in type I and type III Cas proteins.

Development, Feasibility, and Small-Scale Implementation of a Web-Based Prognostic Tool—Surveillance, Epidemiology, and End Results Cancer Survival Calculator

PubMed Central

2017-01-01

Background Population datasets and the Internet are playing an ever-growing role in the way cancer information is made available to providers, patients, and their caregivers. The Surveillance, Epidemiology, and End Results Cancer Survival Calculator (SEER*CSC) is a Web-based cancer prognostic tool that uses SEER data, a large population dataset, to provide physicians with highly valid, evidence-based prognostic estimates for increasing shared decision-making and improving patient-provider communication of complex health information. Objective The aim of this study was to develop, test, and implement SEER*CSC. Methods An iterative approach was used to develop the SEER*CSC. Based on input from cancer patient advocacy groups and physicians, an initial version of the tool was developed. Next, providers from 4 health care delivery systems were recruited to do formal usability testing of SEER*CSC. A revised version of SEER*CSC was then implemented in two health care delivery sites using a real-world clinical implementation approach, and usage data were collected. Post-implementation follow-up interviews were conducted with site champions. Finally, patients from two cancer advocacy groups participated in usability testing. Results Overall feedback of SEER*CSC from both providers and patients was positive, with providers noting that the tool was professional and reliable, and patients finding it to be informational and helpful to use when discussing their diagnosis with their provider. However, use during the small-scale implementation was low. Reasons for low usage included time to enter data, not having treatment options in the tool, and the tool not being incorporated into the electronic health record (EHR). Patients found the language in its current version to be too complex. Conclusions The implementation and usability results showed that participants were enthusiastic about the use and features of SEER*CSC, but sustained implementation in a real-world clinical setting faced significant challenges. As a result of these findings, SEER*CSC is being redesigned with more accessible language for a public facing release. Meta-tools, which put different tools in context of each other, are needed to assist in understanding the strengths and limitations of various tools and their place in the clinical decision-making pathway. The continued development and eventual release of prognostic tools should include feedback from multidisciplinary health care teams, various stakeholder groups, patients, and caregivers. PMID:28729232

Support for the Naval Research Laboratory Environmental Passive Microwave Remote Sensing Program.

DTIC Science & Technology

1983-04-29

L. H. Gesell te _ C= Project Manager ’ . . , . ".."........... . ., . q J ABSTRACT This document summarizes the data acquisition, reduc- tion, and...film camera , and other environmental sensors. CSC gradually assumed the bulk of the responsibility for opera- ting this equipment. This included running...radiometers, and setting up and operating the strip-film camera and other en- vironmental sensors. Also of significant importance to the missions was

Exploring the Influence of 21st Century Skills in a Dual Language Program: A Case Study

ERIC Educational Resources Information Center

Heinrichs, Christine R.

2016-01-01

Preparing students as 21st century learners is a key reform in education. The Partnership for 21st Century Skills developed a framework that identifies outcomes needed for successful implementation of rigorous standards. The Dual Language (DL) program was identified as a structure for reform with systems and practices which can be used to prepare…

The Chandra Source Catalog 2.0: the Galactic center region

NASA Astrophysics Data System (ADS)

Civano, Francesca Maria; Allen, Christopher E.; Anderson, Craig S.; Budynkiewicz, Jamie A.; Burke, Douglas; Chen, Judy C.; D'Abrusco, Raffaele; Doe, Stephen M.; Evans, Ian N.; Evans, Janet D.; Fabbiano, Giuseppina; Gibbs, Danny G., II; Glotfelty, Kenny J.; Graessle, Dale E.; Grier, John D.; Hain, Roger; Hall, Diane M.; Harbo, Peter N.; Houck, John C.; Lauer, Jennifer L.; Laurino, Omar; Lee, Nicholas P.; Martínez-Galarza, Juan Rafael; McCollough, Michael L.; McDowell, Jonathan C.; Miller, Joseph; McLaughlin, Warren; Morgan, Douglas L.; Mossman, Amy E.; Nguyen, Dan T.; Nichols, Joy S.; Nowak, Michael A.; Paxson, Charles; Plummer, David A.; Primini, Francis Anthony; Rots, Arnold H.; Siemiginowska, Aneta; Sundheim, Beth A.; Tibbetts, Michael; Van Stone, David W.; Zografou, Panagoula

2018-01-01

The second release of the Chandra Source Catalog (CSC 2.0) comprises all the 10,382 ACIS and HRC-I imaging observations taken by Chandra and released publicly through the end of 2014. Among these, 534 single observations surrounding the Galactic center are included, covering a total area of ~19deg2 and a total exposure time of ~9 Ms.The single 534 observations were merged into 379 stacks (overlapping observations with aim-points within 60") to increase the flux limit for source detection purposes.Thanks to the combination of the point source detection algorithm with the maximum likelihood technique used to asses the source significance, ~21,000 detections are listed in the CSC 2.0 for this field only, 80% of which are unique sources. The central region of this field around the SgrA* location has the deepest exposure of 2.2 Ms and the highest source density with ~5000 sources. In this poster, we present details about this region including source distribution and density, coverage, exposure.This work has been supported by NASA under contract NAS 8-03060 to the Smithsonian Astrophysical Observatory for operation of the ChandraX-ray Center.

Cinnamides as selective small-molecule inhibitors of a cellular model of breast cancer stem cells.

PubMed

Germain, Andrew R; Carmody, Leigh C; Nag, Partha P; Morgan, Barbara; Verplank, Lynn; Fernandez, Cristina; Donckele, Etienne; Feng, Yuxiong; Perez, Jose R; Dandapani, Sivaraman; Palmer, Michelle; Lander, Eric S; Gupta, Piyush B; Schreiber, Stuart L; Munoz, Benito

2013-03-15

A high-throughput screen (HTS) was conducted against stably propagated cancer stem cell (CSC)-enriched populations using a library of 300,718 compounds from the National Institutes of Health (NIH) Molecular Libraries Small Molecule Repository (MLSMR). A cinnamide analog displayed greater than 20-fold selective inhibition of the breast CSC-like cell line (HMLE_sh_Ecad) over the isogenic control cell line (HMLE_sh_eGFP). Herein, we report structure-activity relationships of this class of cinnamides for selective lethality towards CSC-enriched populations. Copyright © 2013. Published by Elsevier Ltd.

The relation of somatotypes and stress response to central serous chorioretinopathy.

PubMed

Schwartz, Roy; Rozenberg, Assaf; Loewenstein, Anat; Goldstein, Michaella

2017-12-01

To investigate a possible relationship between central serous chorioretinopathy (CSC) and specific body types and compositions (somatotypes), and to examine the cortisol stress response among CSC patients of different somatotypes in comparison with healthy subjects. Prospective case-control study. A group of 28 patients with a previous or current diagnosis of CSC was compared with a group of 26 healthy subjects. Anthropometric measurements were used to estimate somatotype ratings in all subjects. Serum cortisol was measured at rest and following a stress-inducing computerized test in order to estimate response to stress in both groups. The main outcome measures included somatotype categorization and the change in serum cortisol following stress in both groups. No significant difference in somatotype composition was found between the groups. There was no statistically significant difference between the groups in the elevation of cortisol following the stress-inducing test. The sample size was too small to exclude or find any significant difference between the different 13 subgroups of somatotype composition in the elevation of cortisol. Our study did not show a typical somatotype related to CSC. While previous studies showed higher cortisol values in CSC patients, we did not see a higher elevation in blood cortisol following a stress response in this group in comparison with healthy subjects.

A novel sol-gel-derived calcium silicate cement with short setting time for application in endodontic repair of perforations

PubMed Central

Lee, Bor-Shiunn; Lin, Hong-Ping; Chan, Jerry Chun-Chung; Wang, Wei-Chuan; Hung, Ping-Hsuan; Tsai, Yu-Hsin; Lee, Yuan-Ling

2018-01-01

Mineral trioxide aggregate (MTA) is the most frequently used repair material in endodontics, but the long setting time and reduced mechanical strength in acidic environments are major shortcomings. In this study, a novel sol-gel-derived calcium silicate cement (sCSC) was developed using an initial Ca/Si molar ratio of 3, with the most effective mixing orders of reactants and optimal HNO3 catalyst volumes. A Fourier transform infrared spectrometer, scanning electron microscope with energy-dispersive X-ray spectroscopy, and X-ray powder diffractometer were used for material characterization. The setting time, compressive strength, and microhardness of sCSC after hydration in neutral and pH 5 environments were compared with that of MTA. Results showed that sCSC demonstrated porous microstructures with a setting time of ~30 min, and the major components of sCSC were tricalcium silicate, dicalcium silicate, and calcium oxide. The optimal formula of sCSC was sn200, which exhibited significantly higher compressive strength and microhardness than MTA, irrespective of neutral or pH 5 environments. In addition, both sn200 and MTA demonstrated good biocompatibility because cell viability was similar to that of the control. These findings suggest that sn200 merits further clinical study for potential application in endodontic repair of perforations. PMID:29386894

A novel sol-gel-derived calcium silicate cement with short setting time for application in endodontic repair of perforations.

PubMed

Lee, Bor-Shiunn; Lin, Hong-Ping; Chan, Jerry Chun-Chung; Wang, Wei-Chuan; Hung, Ping-Hsuan; Tsai, Yu-Hsin; Lee, Yuan-Ling

2018-01-01

Mineral trioxide aggregate (MTA) is the most frequently used repair material in endodontics, but the long setting time and reduced mechanical strength in acidic environments are major shortcomings. In this study, a novel sol-gel-derived calcium silicate cement (sCSC) was developed using an initial Ca/Si molar ratio of 3, with the most effective mixing orders of reactants and optimal HNO 3 catalyst volumes. A Fourier transform infrared spectrometer, scanning electron microscope with energy-dispersive X-ray spectroscopy, and X-ray powder diffractometer were used for material characterization. The setting time, compressive strength, and microhardness of sCSC after hydration in neutral and pH 5 environments were compared with that of MTA. Results showed that sCSC demonstrated porous microstructures with a setting time of ~30 min, and the major components of sCSC were tricalcium silicate, dicalcium silicate, and calcium oxide. The optimal formula of sCSC was sn200, which exhibited significantly higher compressive strength and microhardness than MTA, irrespective of neutral or pH 5 environments. In addition, both sn200 and MTA demonstrated good biocompatibility because cell viability was similar to that of the control. These findings suggest that sn200 merits further clinical study for potential application in endodontic repair of perforations.

Direct observation of the effects of cellulose synthesis inhibitors using live cell imaging of Cellulose Synthase (CESA) in Physcomitrella patens.

PubMed

Tran, Mai L; McCarthy, Thomas W; Sun, Hao; Wu, Shu-Zon; Norris, Joanna H; Bezanilla, Magdalena; Vidali, Luis; Anderson, Charles T; Roberts, Alison W

2018-01-15

Results from live cell imaging of fluorescently tagged Cellulose Synthase (CESA) proteins in Cellulose Synthesis Complexes (CSCs) have enhanced our understanding of cellulose biosynthesis, including the mechanisms of action of cellulose synthesis inhibitors. However, this method has been applied only in Arabidopsis thaliana and Brachypodium distachyon thus far. Results from freeze fracture electron microscopy of protonemal filaments of the moss Funaria hygrometrica indicate that a cellulose synthesis inhibitor, 2,6-dichlorobenzonitrile (DCB), fragments CSCs and clears them from the plasma membrane. This differs from Arabidopsis, in which DCB causes CSC accumulation in the plasma membrane and a different cellulose synthesis inhibitor, isoxaben, clears CSCs from the plasma membrane. In this study, live cell imaging of the moss Physcomitrella patens indicated that DCB and isoxaben have little effect on protonemal growth rates, and that only DCB causes tip rupture. Live cell imaging of mEGFP-PpCESA5 and mEGFP-PpCESA8 showed that DCB and isoxaben substantially reduced CSC movement, but had no measureable effect on CSC density in the plasma membrane. These results suggest that DCB and isoxaben have similar effects on CSC movement in P. patens and Arabidopsis, but have different effects on CSC intracellular trafficking, cell growth and cell integrity in these divergent plant lineages.

The Chandra Source Catalog 2.0: Early Cross-matches

NASA Astrophysics Data System (ADS)

Rots, Arnold H.; Allen, Christopher E.; Anderson, Craig S.; Budynkiewicz, Jamie A.; Burke, Douglas; Chen, Judy C.; Civano, Francesca Maria; D'Abrusco, Raffaele; Doe, Stephen M.; Evans, Ian N.; Evans, Janet D.; Fabbiano, Giuseppina; Gibbs, Danny G., II; Glotfelty, Kenny J.; Graessle, Dale E.; Grier, John D.; Hain, Roger; Hall, Diane M.; Harbo, Peter N.; Houck, John C.; Lauer, Jennifer L.; Laurino, Omar; Lee, Nicholas P.; Martínez-Galarza, Rafael; McCollough, Michael L.; McDowell, Jonathan C.; Miller, Joseph; McLaughlin, Warren; Morgan, Douglas L.; Mossman, Amy E.; Nguyen, Dan T.; Nichols, Joy S.; Nowak, Michael A.; Paxson, Charles; Plummer, David A.; Primini, Francis Anthony; Siemiginowska, Aneta; Sundheim, Beth A.; Tibbetts, Michael; Van Stone, David W.; Zografou, Panagoula

2018-01-01

Cross-matching the Chandra Source Catalog (CSC) with other catalogs presents considerable challenges, since the Point Spread Function (PSF) of the Chandra X-ray Observatory varies significantly over the field of view. For the second release of the CSC (CSC2) we have been developing a cross-match tool that is based on the Bayesian algorithms by Budavari, Heinis, and Szalay (ApJ 679, 301 and 705, 739), making use of the error ellipses for the derived positions of the sources.However, calculating match probabilities only on the basis of error ellipses breaks down when the PSFs are significantly different. Not only can bonafide matches easily be missed, but the scene is also muddied by ambiguous multiple matches. These are issues that are not commonly addressed in cross-match tools. We have applied a satisfactory modification to the algorithm that, although not perfect, ameliorates the problems for the vast majority of such cases.We will present some early cross-matches of the CSC2 catalog with obvious candidate catalogs and report on the determination of the absolute astrometric error of the CSC2 based on such cross-matches.This work has been supported by NASA under contract NAS 8-03060 to the Smithsonian Astrophysical Observatory for operation of the Chandra X-ray Center.

Effects of Cetuximab and Erlotinib on the behaviour of cancer stem cells in head and neck squamous cell carcinoma.

PubMed

Setúbal Destro Rodrigues, Maria Fernanda; Gammon, Luke; Rahman, Muhammad M; Biddle, Adrian; Nunes, Fabio Daumas; Mackenzie, Ian C

2018-03-02

The therapeutic responses of many solid tumours to chemo- and radio-therapies are far from fully effective but therapies targeting malignancy-related cellular changes show promise for further control. In head and neck squamous cell carcinoma, the epidermal growth factor receptor (EGFR) is commonly overexpressed and investigation of agents that block this receptor indicate a limited response when used alone but an ability to enhance the actions of other drugs. The hierarchical stem cell patterns present in tumours generate cellular heterogeneity and this is further complicated by cancer stem cells (CSC) shifting between epithelial (Epi-CSC) and mesenchymal (EMT-CSC) states. To clarify how such heterogeneity influences responses to EGFR blocking, we examined the effects of Cetuximab and Erlotinib on the cell sub-populations in HNSCC cell lines. These agents reduced cell proliferation for all subpopulations but induced little cell death. They did however induce large shifts of cells between the EMT-CSC, Epi-CSC and differentiating cell compartments. Loss of EMT-CSCs reduced cell motility and is expected to reduce invasion and metastasis. EGFR blocking also induced shifts of Epi-CSCs into the differentiating cell compartment which typically has greater sensitivity to chemo/radiation, an effect expected to enhance the overall response of tumour cell populations to adjunctive therapies.

Antitumor immunity and cancer stem cells.

PubMed

Schatton, Tobias; Frank, Markus H

2009-09-01

Self-renewing cancer stem cells (CSC) capable of spawning more differentiated tumor cell progeny are required for tumorigenesis and neoplastic progression of leukemias and several solid cancers. The mechanisms by which CSC cause tumor initiation and growth are currently unknown. Recent findings that suggest a negative correlation between degrees of host immunocompetence and rates of cancer development raise the possibility that only a restricted minority of malignant cells, namely CSC, may possess the phenotypic and functional characteristics to evade host antitumor immunity. In human malignant melanoma, a highly immunogenic cancer, we recently identified malignant melanoma initiating cells (MMIC), a novel type of CSC, based on selective expression of the chemoresistance mediator ABCB5. Here we present evidence of a relative immune privilege of ABCB5(+) MMIC, suggesting refractoriness to current immunotherapeutic treatment strategies. We discuss our findings in the context of established immunomodulatory functions of physiologic stem cells and in relation to mechanisms responsible for the downregulation of immune responses against tumors. We propose that the MMIC subset might be responsible for melanoma immune evasion and that immunomodulation might represent one mechanism by which CSC advance tumorigenic growth and resistance to immunotherapy. Accordingly, the possibility of an MMIC-driven tumor escape from immune-mediated rejection has important implications for current melanoma immunotherapy.

Antitumor Immunity and Cancer Stem Cells

PubMed Central

Schatton, Tobias; Frank, Markus H.

2010-01-01

Self-renewing cancer stem cells (CSC) capable of spawning more differentiated tumor cell progeny are required for tumorigenesis and neoplastic progression of leukemias and several solid cancers. The mechanisms by which CSC cause tumor initiation and growth are currently unknown. Recent findings that suggest a negative correlation between degrees of host immunocompetence and rates of cancer development raise the possibility that only a restricted minority of malignant cells, namely CSC, may possess the phenotypic and functional characteristics to evade host antitumor immunity. In human malignant melanoma, a highly immunogenic cancer, we recently identified malignant melanoma initiating cells (MMIC), a novel type of CSC, based on selective expression of the chemoresistance mediator ABCB5. Here we present evidence of a relative immune privilege of ABCB5+ MMIC, suggesting refractoriness to current immunotherapeutic treatment strategies. We discuss our findings in the context of established immunomodulatory functions of physiologic stem cells and in relation to mechanisms responsible for the downregulation of immune responses against tumors. We propose that the MMIC subset might be responsible for melanoma immune evasion and that immunomodulation might represent one mechanism by which CSC advance tumorigenic growth and resistance to immunotherapy. Accordingly, the possibility of an MMIC-driven tumor escape from immune-mediated rejection has important implications for current melanoma immunotherapy. PMID:19796244

Effects of Cetuximab and Erlotinib on the behaviour of cancer stem cells in head and neck squamous cell carcinoma

PubMed Central

Setúbal Destro Rodrigues, Maria Fernanda; Gammon, Luke; Rahman, Muhammad M.; Biddle, Adrian; Nunes, Fabio Daumas; Mackenzie, Ian C.

2018-01-01

The therapeutic responses of many solid tumours to chemo- and radio-therapies are far from fully effective but therapies targeting malignancy-related cellular changes show promise for further control. In head and neck squamous cell carcinoma, the epidermal growth factor receptor (EGFR) is commonly overexpressed and investigation of agents that block this receptor indicate a limited response when used alone but an ability to enhance the actions of other drugs. The hierarchical stem cell patterns present in tumours generate cellular heterogeneity and this is further complicated by cancer stem cells (CSC) shifting between epithelial (Epi-CSC) and mesenchymal (EMT-CSC) states. To clarify how such heterogeneity influences responses to EGFR blocking, we examined the effects of Cetuximab and Erlotinib on the cell sub-populations in HNSCC cell lines. These agents reduced cell proliferation for all subpopulations but induced little cell death. They did however induce large shifts of cells between the EMT-CSC, Epi-CSC and differentiating cell compartments. Loss of EMT-CSCs reduced cell motility and is expected to reduce invasion and metastasis. EGFR blocking also induced shifts of Epi-CSCs into the differentiating cell compartment which typically has greater sensitivity to chemo/radiation, an effect expected to enhance the overall response of tumour cell populations to adjunctive therapies. PMID:29568372

Increased anxiety, voluntary alcohol consumption and ethanol-induced place preference in mice following chronic psychosocial stress.

PubMed

Bahi, Amine

2013-07-01

Stress exposure is known to be a risk factor for alcohol use and anxiety disorders. Comorbid chronic stress and alcohol dependence may lead to a complicated and potentially severe treatment profile. To gain an understanding of the interaction between chronic psychosocial stress and drug exposure, we studied the effects of concomitant chronic stress exposure on alcohol reward using two-bottle choice and ethanol-conditioned place preference (CPP). The study consisted of exposure of the chronic subordinate colony (CSC) mice "intruders" to an aggressive "resident" mouse for 19 consecutive days. Control mice were single housed (SHC). Ethanol consumption using two-bottle choice paradigm and ethanol CPP acquisition was assessed at the end of this time period. As expected, CSC exposure increased anxiety-like behavior and reduced weight gain as compared to SHC controls. Importantly, in the two-bottle choice procedure, CSC mice showed higher alcohol intake than SHC. When testing their response to ethanol-induced CPP, CSC mice achieved higher preference for the ethanol-paired chamber. In fact, CSC exposure increased ethanol-CPP acquisition. Taken together, these data demonstrate the long-term consequences of chronic psychosocial stress on alcohol intake in male mice, suggesting chronic stress as a risk factor for developing alcohol consumption and/or anxiety disorders.

Working alliance inventory applied to virtual and augmented reality (WAI-VAR): psychometrics and therapeutic outcomes

PubMed Central

Miragall, Marta; Baños, Rosa M.; Cebolla, Ausiàs; Botella, Cristina

2015-01-01

This study examines the psychometric properties of the Working Alliance Inventory-Short (WAI-S) adaptation to Virtual Reality (VR) and Augmented Reality (AR) therapies (WAI-VAR). The relationship between the therapeutic alliance (TA) with VR and AR and clinically significant change (CSC) is also explored. Seventy-five patients took part in this study (74.7% women, Mage = 34.41). Fear of flying and adjustment disorder patients received VR therapy, and cockroach phobia patients received AR therapy. Psychometric properties, CSC, one-way ANOVA, Spearman’s Correlations and Multiple Regression were calculated. The WAI-VAR showed a unidimensional structure, high internal consistency and adequate convergent validity. “Not changed” patients scored lower on the WAI-VAR than “improved” and “recovered” patients. Correlation between the WAI-VAR and CSC was moderate. The best fitting model for predicting CSC was a linear combination of the TA with therapist (WAI-S) and the TA with VR and AR (WAI-VAR), due to the latter variable slightly increased the percentage of variability accounted for in CSC. The WAI-VAR is the first validated instrument to measure the TA with VR and AR in research and clinical practice. This study reveals the importance of the quality of the TA with technologies in achieving positive outcomes in the therapy. PMID:26500589

Working alliance inventory applied to virtual and augmented reality (WAI-VAR): psychometrics and therapeutic outcomes.

PubMed

Miragall, Marta; Baños, Rosa M; Cebolla, Ausiàs; Botella, Cristina

2015-01-01

This study examines the psychometric properties of the Working Alliance Inventory-Short (WAI-S) adaptation to Virtual Reality (VR) and Augmented Reality (AR) therapies (WAI-VAR). The relationship between the therapeutic alliance (TA) with VR and AR and clinically significant change (CSC) is also explored. Seventy-five patients took part in this study (74.7% women, M age = 34.41). Fear of flying and adjustment disorder patients received VR therapy, and cockroach phobia patients received AR therapy. Psychometric properties, CSC, one-way ANOVA, Spearman's Correlations and Multiple Regression were calculated. The WAI-VAR showed a unidimensional structure, high internal consistency and adequate convergent validity. "Not changed" patients scored lower on the WAI-VAR than "improved" and "recovered" patients. Correlation between the WAI-VAR and CSC was moderate. The best fitting model for predicting CSC was a linear combination of the TA with therapist (WAI-S) and the TA with VR and AR (WAI-VAR), due to the latter variable slightly increased the percentage of variability accounted for in CSC. The WAI-VAR is the first validated instrument to measure the TA with VR and AR in research and clinical practice. This study reveals the importance of the quality of the TA with technologies in achieving positive outcomes in the therapy.

Stem cells as the root of pancreatic ductal adenocarcinoma

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

Balic, Anamaria; Dorado, Jorge; Alonso-Gomez, Mercedes

2012-04-01

Emerging evidence suggests that stem cells play a crucial role not only in the generation and maintenance of different tissues, but also in the development and progression of malignancies. For the many solid cancers, it has now been shown that they harbor a distinct subpopulation of cancer cells that bear stem cell features and therefore, these cells are termed cancer stem cells (CSC) or tumor-propagating cells. CSC are exclusively tumorigenic and essential drivers for tumor progression and metastasis. Moreover, it has been shown that pancreatic ductal adenocarcinoma does not only contain one homogeneous population of CSC rather than diverse subpopulationsmore » that may have evolved during tumor progression. One of these populations is called migrating CSC and can be characterized by CXCR4 co-expression. Only these cells are capable of evading the primary tumor and traveling to distant sites such as the liver as the preferred site of metastatic spread. Clinically even more important, however, is the observation that CSC are highly resistant to chemo- and radiotherapy resulting in their relative enrichment during treatment and rapid relapse of disease. Many laboratories are now working on the further in-depth characterization of these cells, which may eventually allow for the identification of their Achilles heal and lead to novel treatment modalities for fighting this deadly disease.« less

Caryophyllane sesquiterpenes inhibit DNA-damage by tobacco smoke in bacterial and mammalian cells.

PubMed

Di Giacomo, Silvia; Abete, Lorena; Cocchiola, Rossana; Mazzanti, Gabriela; Eufemi, Margherita; Di Sotto, Antonella

2018-01-01

In the present study, the ability of the natural sesquiterpene β-caryophyllene (CRY) and its metabolite β-caryophyllene oxide (CRYO) to inhibit the genotoxicity of a condensate of cigarette smoke (CSC) was evaluated both in bacterial and mammalian cells. Also, the inhibition of the CSC-mediated STAT3 phosphorylation and intracellular oxidative stress was evaluated as potential chemopreventive mechanism. Under our experimental conditions, both the sesquiterpenes exhibited antimutagenic properties, being CRY the most potent compound. The antimutagenicity was highlighted in all experimental protocols, being particularly strong in the co- and post-treatments. The test substances also reduced the micronuclei frequency induced by CSC, with a major effectiveness of CRY. CRY was also able to reduce the CSC-mediated increase of the Y705- pSTAT3 levels, in spite of a lacking effect of CRYO. Furthermore, the sesquiterpenes CRY and CRYO displayed a moderate antioxidant activity, with a 25 % and 40 % inhibition of the ROS-levels increased by CSC, respectively. On the basis of these results, CRY seems to be a multi-target chemopreventive agent, although the genoprotective and antioxidant effects of CRYO suggest that both compounds deserve to be deeply investigated for a possible application in the prevention and treatment of different smoke-related ailments. Copyright © 2017 Elsevier Ltd. All rights reserved.

Cancer stem cell drugs target K-ras signaling in a stemness context

PubMed Central

Najumudeen, A K; Jaiswal, A; Lectez, B; Oetken-Lindholm, C; Guzmán, C; Siljamäki, E; Posada, I M D; Lacey, E; Aittokallio, T; Abankwa, D

2016-01-01

Cancer stem cells (CSCs) are considered to be responsible for treatment relapse and have therefore become a major target in cancer research. Salinomycin is the most established CSC inhibitor. However, its primary mechanistic target is still unclear, impeding the discovery of compounds with similar anti-CSC activity. Here, we show that salinomycin very specifically interferes with the activity of K-ras4B, but not H-ras, by disrupting its nanoscale membrane organization. We found that caveolae negatively regulate the sensitivity to this drug. On the basis of this novel mechanistic insight, we defined a K-ras-associated and stem cell-derived gene expression signature that predicts the drug response of cancer cells to salinomycin. Consistent with therapy resistance of CSC, 8% of tumor samples in the TCGA-database displayed our signature and were associated with a significantly higher mortality. Using our K-ras-specific screening platform, we identified several new candidate CSC drugs. Two of these, ophiobolin A and conglobatin A, possessed a similar or higher potency than salinomycin. Finally, we established that the most potent compound, ophiobolin A, exerts its K-ras4B-specific activity through inactivation of calmodulin. Our data suggest that specific interference with the K-ras4B/calmodulin interaction selectively inhibits CSC. PMID:26973241

Pathways to Change: Improving the Quality of Education in Developing Countries. World Bank Discussion Papers 53.

ERIC Educational Resources Information Center

Verspoor, Adriaan

A review of 21 educational change programs supported by 42 World Bank-assisted projects found that the most successful programs have a different profile than the less successful programs. The former aimed at comprehensive change, encompassing a wide range of objectives including administrative and management training and the provision of…

Characterization of aldehyde dehydrogenase 1 high ovarian cancer cells: Towards targeted stem cell therapy.

PubMed

Sharrow, Allison C; Perkins, Brandy; Collector, Michael I; Yu, Wayne; Simons, Brian W; Jones, Richard J

2016-08-01

The cancer stem cell (CSC) paradigm hypothesizes that successful clinical eradication of CSCs may lead to durable remission for patients with ovarian cancer. Despite mounting evidence in support of ovarian CSCs, their phenotype and clinical relevance remain unclear. We and others have found high aldehyde dehydrogenase 1 (ALDH(high)) expression in a variety of normal and malignant stem cells, and sought to better characterize ALDH(high) cells in ovarian cancer. We compared ALDH(high) to ALDH(low) cells in two ovarian cancer models representing distinct subtypes: FNAR-C1 cells, derived from a spontaneous rat endometrioid carcinoma, and the human SKOV3 cell line (described as both serous and clear cell subtypes). We assessed these populations for stem cell features then analyzed expression by microarray and qPCR. ALDH(high) cells displayed CSC properties, including: smaller size, quiescence, regenerating the phenotypic diversity of the cell lines in vitro, lack of contact inhibition, nonadherent growth, multi-drug resistance, and in vivo tumorigenicity. Microarray and qPCR analysis of the expression of markers reported by others to enrich for ovarian CSCs revealed that ALDH(high) cells of both models showed downregulation of CD24, but inconsistent expression of CD44, KIT and CD133. However, the following druggable targets were consistently expressed in the ALDH(high) cells from both models: mTOR signaling, her-2/neu, CD47 and FGF18/FGFR3. Based on functional characterization, ALDH(high) ovarian cancer cells represent an ovarian CSC population. Differential gene expression identified druggable targets that have the potential for therapeutic efficacy against ovarian CSCs from multiple subtypes. Copyright © 2016 Elsevier Inc. All rights reserved.

Curcumin Chemosensitizes 5-Fluorouracil Resistant MMR-Deficient Human Colon Cancer Cells in High Density Cultures

PubMed Central

Shakibaei, Mehdi; Buhrmann, Constanze; Kraehe, Patricia; Shayan, Parviz; Lueders, Cora; Goel, Ajay

2014-01-01

Objective Treatment of colorectal cancer (CRC) remains a clinical challenge, as more than 15% of patients are resistant to 5-Fluorouracil (5-FU)-based chemotherapeutic regimens, and tumor recurrence rates can be as high as 50–60%. Cancer stem cells (CSC) are capable of surviving conventional chemotherapies that permits regeneration of original tumors. Therefore, we investigated the effectiveness of 5-FU and plant polyphenol (curcumin) in context of DNA mismatch repair (MMR) status and CSC activity in 3D cultures of CRC cells. Methods High density 3D cultures of CRC cell lines HCT116, HCT116+ch3 (complemented with chromosome 3) and their corresponding isogenic 5-FU-chemo-resistant derivative clones (HCT116R, HCT116+ch3R) were treated with 5-FU either without or with curcumin in time- and dose-dependent assays. Results Pre-treatment with curcumin significantly enhanced the effect of 5-FU on HCT116R and HCR116+ch3R cells, in contrast to 5-FU alone as evidenced by increased disintegration of colonospheres, enhanced apoptosis and by inhibiting their growth. Curcumin and/or 5-FU strongly affected MMR-deficient CRC cells in high density cultures, however MMR-proficient CRC cells were more sensitive. These effects of curcumin in enhancing chemosensitivity to 5-FU were further supported by its ability to effectively suppress CSC pools as evidenced by decreased number of CSC marker positive cells, highlighting the suitability of this 3D culture model for evaluating CSC marker expression in a close to vivo setting. Conclusion Our results illustrate novel and previously unrecognized effects of curcumin in enhancing chemosensitization to 5-FU-based chemotherapy on DNA MMR-deficient and their chemo-resistant counterparts by targeting the CSC sub-population. (246 words in abstract). PMID:24404205

Curcumin chemosensitizes 5-fluorouracil resistant MMR-deficient human colon cancer cells in high density cultures.

PubMed

Shakibaei, Mehdi; Buhrmann, Constanze; Kraehe, Patricia; Shayan, Parviz; Lueders, Cora; Goel, Ajay

2014-01-01

Treatment of colorectal cancer (CRC) remains a clinical challenge, as more than 15% of patients are resistant to 5-Fluorouracil (5-FU)-based chemotherapeutic regimens, and tumor recurrence rates can be as high as 50-60%. Cancer stem cells (CSC) are capable of surviving conventional chemotherapies that permits regeneration of original tumors. Therefore, we investigated the effectiveness of 5-FU and plant polyphenol (curcumin) in context of DNA mismatch repair (MMR) status and CSC activity in 3D cultures of CRC cells. High density 3D cultures of CRC cell lines HCT116, HCT116+ch3 (complemented with chromosome 3) and their corresponding isogenic 5-FU-chemo-resistant derivative clones (HCT116R, HCT116+ch3R) were treated with 5-FU either without or with curcumin in time- and dose-dependent assays. Pre-treatment with curcumin significantly enhanced the effect of 5-FU on HCT116R and HCR116+ch3R cells, in contrast to 5-FU alone as evidenced by increased disintegration of colonospheres, enhanced apoptosis and by inhibiting their growth. Curcumin and/or 5-FU strongly affected MMR-deficient CRC cells in high density cultures, however MMR-proficient CRC cells were more sensitive. These effects of curcumin in enhancing chemosensitivity to 5-FU were further supported by its ability to effectively suppress CSC pools as evidenced by decreased number of CSC marker positive cells, highlighting the suitability of this 3D culture model for evaluating CSC marker expression in a close to vivo setting. Our results illustrate novel and previously unrecognized effects of curcumin in enhancing chemosensitization to 5-FU-based chemotherapy on DNA MMR-deficient and their chemo-resistant counterparts by targeting the CSC sub-population. (246 words in abstract).

Bitter melon juice exerts its efficacy against pancreatic cancer via targeting both bulk and cancer stem cells.

PubMed

Dhar, Deepanshi; Deep, Gagan; Kumar, Sushil; Wempe, Michael F; Raina, Komal; Agarwal, Chapla; Agarwal, Rajesh

2018-05-04

Pancreatic cancer (PanC) is one of the deadliest malignancies worldwide and frontline treatment with gemcitabine becomes eventually ineffective due to increasing PanC resistance, suggesting additional approaches are needed to manage PanC. Recently, we have shown the efficacy of bitter melon juice (BMJ) against PanC cells, including those resistant to gemcitabine. Since cancer stem cells (CSCs) are actively involved in PanC initiation, progression, relapse and drug-resistance, here we assessed BMJ ability in targeting pancreatic cancer-associated cancer stem cells (PanC-CSCs). We found BMJ efficacy against CD44 + /CD24 + /EpCAM high enriched PanC-CSCs in spheroid assays; BMJ also increased the sensitivity of gemcitabine-resistant PanC-CSCs. Exogenous addition of BMJ to PanC-CSC generated spheroids (not pre-exposed to BMJ) also significantly reduced spheroid number and size. Mechanistically, BMJ effects were associated with a decrease in the expression of genes and proteins involved in PanC-CSC renewal and proliferation. Specifically, immunofluorescence staining showed that BMJ decreases protein expression/nuclear localization of CSC-associated transcription factors SOX2, OCT4 and NANOG, and CSC marker CD44. Immunohistochemical analysis of MiaPaCa2 xenografts from BMJ treated animals also showed a significant decrease in the levels of CSC-associated transcription factors. Together, these results show BMJ potential in targeting PanC-CSC pool and associated regulatory pathways, suggesting the need for further investigation of its efficacy against PanC growth and progression including gemcitabine-resistant PanC. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Anti-cell growth and anti-cancer stem cell activities of the non-canonical hedgehog inhibitor GANT61 in triple-negative breast cancer cells.

PubMed

Koike, Yoshikazu; Ohta, Yusuke; Saitoh, Wataru; Yamashita, Tetsumasa; Kanomata, Naoki; Moriya, Takuya; Kurebayashi, Junichi

2017-09-01

Triple-negative breast cancer (TNBC) exhibits biologically aggressive behavior and has a poor prognosis. Novel molecular targeting agents are needed to control TNBC. Recent studies revealed that the non-canonical hedgehog (Hh) signaling pathway plays important roles in the regulation of cancer stem cells (CSCs) in breast cancer. Therefore, the anti-cell growth and anti-CSC effects of the non-canonical Hh inhibitor GANT61 were investigated in TNBC cells. The effects of GANT61 on cell growth, cell cycle progression, apoptosis, and the proportion of CSCs were investigated in three TNBC cell lines. Four ER-positive breast cancer cell lines were also used for comparisons. The expression levels of effector molecules in the Hh pathway: glioma-associated oncogene (GLI) 1 and GLI2, were measured. The combined effects of GANT61 and paclitaxel on anti-cell growth and anti-CSC activities were also investigated. Basal expression levels of GLI1 and GLI2 were significantly higher in TNBC cells than in ER-positive breast cancer cells. GANT61 dose-dependently decreased cell growth in association with G1-S cell cycle retardation and increased apoptosis. GANT61 significantly decreased the CSC proportion in all TNBC cell lines. Paclitaxel decreased cell growth, but not the CSC proportion. Combined treatments of GANT61 and paclitaxel more than additively enhanced anti-cell growth and/or anti-CSC activities. The non-canonical Hh inhibitor GANT61 decreased not only cell growth, but also the CSC population in TNBC cells. GANT61 enhanced the anti-cell growth activity of paclitaxel in these cells. These results suggest for the first time that GANT61 has potential as a therapeutic agent in the treatment of patients with TNBC.

tPA Prescription and Administration Errors within a Regional Stroke System

PubMed Central

Chung, Lee S; Tkach, Aleksander; Lingenfelter, Erin M; Dehoney, Sarah; Rollo, Jeannie; de Havenon, Adam; DeWitt, Lucy Dana; Grantz, Matthew Ryan; Wang, Haimei; Wold, Jana J; Hannon, Peter M; Weathered, Natalie R; Majersik, Jennifer J

2015-01-01

Background IV tPA utilization in acute ischemic stroke (AIS) requires weight-based dosing and a standardized infusion rate. In our regional network, we have tried to minimize tPA dosing errors. We describe the frequency and types of tPA administration errors made in our comprehensive stroke center (CSC) and at community hospitals (CHs) prior to transfer. Methods Using our stroke quality database, we extracted clinical and pharmacy information on all patients who received IV tPA from 2010–11 at the CSC or CH prior to transfer. All records were analyzed for the presence of inclusion/exclusion criteria deviations or tPA errors in prescription, reconstitution, dispensing, or administration, and analyzed for association with outcomes. Results We identified 131 AIS cases treated with IV tPA: 51% female; mean age 68; 32% treated at CSC, 68% at CH (including 26% by telestroke) from 22 CHs. tPA prescription and administration errors were present in 64% of all patients (41% CSC, 75% CH, p<0.001), the most common being incorrect dosage for body weight (19% CSC, 55% CH, p<0.001). Of the 27 overdoses, there were 3 deaths due to systemic hemorrhage or ICH. Nonetheless, outcomes (parenchymal hematoma, mortality, mRS) did not differ between CSC and CH patients nor between those with and without errors. Conclusion Despite focus on minimization of tPA administration errors in AIS patients, such errors were very common in our regional stroke system. Although an association between tPA errors and stroke outcomes was not demonstrated, quality assurance mechanisms are still necessary to reduce potentially dangerous, avoidable errors. PMID:26698642

Communication in conversation in stroke patients.

PubMed

Rousseaux, Marc; Daveluy, Walter; Kozlowski, Odile

2010-07-01

In stroke patients, it has been suggested that communication disorders could result from lexical and syntactic disorders in left hemisphere lesions and from pragmatics problems in right lesions. However, we have little information on patient behaviour in dyadic communication, especially in conversation. Here, we analyzed the various processes participating in communication difficulties at the rehabilitation phase (1-6 months) post-stroke, in order to define the main mechanisms of verbal and non-verbal communication (VC, NVC) disorders and their relationship with aphasic disorders. Sixty-three patients were recruited, who belonged to six groups, with left or right cortico-sub-cortical (L-CSC, R-CSC) or sub-cortical (L-SC, R-SC), frontal (Fro) or posterior fossa (PF) lesions. They were compared with an equivalent control group (gender, age, education level). We used the Lille Communication Test, which comprises three parts: participation to communication (greeting, attention, engagement), verbal communication (verbal comprehension, speech outflow, intelligibility, word production, syntax, verbal pragmatics and verbal feedback) and non-verbal communication (understanding gestures, affective expressivity, producing gestures, pragmatics and feedback). We also used the Functional Communication Profile and the Boston Diagnostic Aphasia Examination (BDAE). Decrease in participation was found in L-CSC, R-CSC and Fro patients. Verbal communication was essentially disrupted in L-SCS and L-SC groups, including by verbal pragmatic disorders, and to a lesser degree in frontal patients. Nonverbal communication was mainly affected in R-CSC patients, especially by pragmatic difficulties. L-CSC patients showed an increase in gesture production, compensating for aphasia. In conclusion, communication disorders were relatively complex and could not be summarised by syntactical and lexical difficulties in left stroke and pragmatic problems in right stroke. The former also showed severe verbal pragmatic difficulties. Frontal stroke also resulted in evident verbal and non-verbal disorders.

Statistical Characterization of the Chandra Source Catalog

NASA Astrophysics Data System (ADS)

Primini, Francis A.; Houck, John C.; Davis, John E.; Nowak, Michael A.; Evans, Ian N.; Glotfelty, Kenny J.; Anderson, Craig S.; Bonaventura, Nina R.; Chen, Judy C.; Doe, Stephen M.; Evans, Janet D.; Fabbiano, Giuseppina; Galle, Elizabeth C.; Gibbs, Danny G.; Grier, John D.; Hain, Roger M.; Hall, Diane M.; Harbo, Peter N.; He, Xiangqun Helen; Karovska, Margarita; Kashyap, Vinay L.; Lauer, Jennifer; McCollough, Michael L.; McDowell, Jonathan C.; Miller, Joseph B.; Mitschang, Arik W.; Morgan, Douglas L.; Mossman, Amy E.; Nichols, Joy S.; Plummer, David A.; Refsdal, Brian L.; Rots, Arnold H.; Siemiginowska, Aneta; Sundheim, Beth A.; Tibbetts, Michael S.; Van Stone, David W.; Winkelman, Sherry L.; Zografou, Panagoula

2011-06-01

The first release of the Chandra Source Catalog (CSC) contains ~95,000 X-ray sources in a total area of 0.75% of the entire sky, using data from ~3900 separate ACIS observations of a multitude of different types of X-ray sources. In order to maximize the scientific benefit of such a large, heterogeneous data set, careful characterization of the statistical properties of the catalog, i.e., completeness, sensitivity, false source rate, and accuracy of source properties, is required. Characterization efforts of other large Chandra catalogs, such as the ChaMP Point Source Catalog or the 2 Mega-second Deep Field Surveys, while informative, cannot serve this purpose, since the CSC analysis procedures are significantly different and the range of allowable data is much less restrictive. We describe here the characterization process for the CSC. This process includes both a comparison of real CSC results with those of other, deeper Chandra catalogs of the same targets and extensive simulations of blank-sky and point-source populations.

Repeated Administration of Cigarette Smoke Condensate Increases Glutamate Levels and Behavioral Sensitization

PubMed Central

Ryu, In Soo; Kim, Jieun; Seo, Su Yeon; Yang, Ju Hwan; Oh, Jeong Hwan; Lee, Dong Kun; Cho, Hyun-Wook; Lee, Kyuhong; Yoon, Seong Shoon; Seo, Joung-Wook; Shim, Insop; Choe, Eun Sang

2018-01-01

Nicotine, a nicotinic acetylcholine receptor agonist, produces the reinforcing effects of tobacco dependence by potentiating dopaminergic and glutamatergic neurotransmission. Non-nicotine alkaloids in tobacco also contribute to dependence by activating the cholinergic system. However, glutamatergic neurotransmission in the dorsal striatum associated with behavioral changes in response to cigarette smoking has not been investigated. In this study, the authors investigated alterations in glutamate levels in the rat dorsal striatum related to behavioral alterations after repeated administration of cigarette smoke condensate (CSC) using the real-time glutamate biosensing and an open-field behavioral assessment. Repeated administration of CSC including 0.4 mg nicotine (1.0 mL/kg/day, subcutaneous) for 14 days significantly increased extracellular glutamate concentrations more than repeated nicotine administration. In parallel with the hyperactivation of glutamate levels, repeated administration of CSC-evoked prolonged hypersensitization of psychomotor activity, including locomotor and rearing activities. These findings suggest that the CSC-induced psychomotor activities are closely associated with the elevation of glutamate concentrations in the rat dorsal striatum. PMID:29615877

Sympathetic Chain Schwannoma Resembling Carotid Body Tumour.

PubMed

Najeeb, Tallat; Khan, Musaddiq

2016-06-01

Schwannomas are rare, benign nerve sheath tumours of parapharyngeal space. Differential diagnosis should include salivary gland tumours, paragangliomas, neurofibromas, and metastatic lymph nodes. The tumours may arise from vagus nerve and cervical sympathetic chain (CSC). Diagnosis is usually made by imaging techniques: contrast CT, magnetic resonance imaging (MRI), and magnetic resonance angiography (MRA). Fine needle aspiration cytology (FNAC) is useful diagnostic procedure but poor results are seen in neurogenic tumours. Rarely, a vascular CSC schwannoma at the level of carotid arteries bifurcation may mimic carotid body tumour (CBT) on imaging techniques, especially if they are vascular, causing splaying of internal and external carotid arteries. Clinically patient was asymptomatic except for a pulsatile swelling in neck for 5 years. The presented case resembled CBTclinically, on ultrasound and on imaging techniques causing splaying of carotid arteries. FNAC was inconclusive and was always hemorrhagic. During operation, it was found to be CSC schwannoma just posterior to carotid body. CSC was sacrificed and patient developed Horner syndrome postoperatively.

Risk of Clinically Significant Prostate Cancer Associated With Prostate Imaging Reporting and Data System Category 3 (Equivocal) Lesions Identified on Multiparametric Prostate MRI.

PubMed

Sheridan, Alison D; Nath, Sameer K; Syed, Jamil S; Aneja, Sanjay; Sprenkle, Preston C; Weinreb, Jeffrey C; Spektor, Michael

2018-02-01

The objective of this study is to determine the frequency of clinically significant cancer (CSC) in Prostate Imaging Reporting and Data System (PI-RADS) category 3 (equivocal) lesions prospectively identified on multiparametric prostate MRI and to identify risk factors (RFs) for CSC that may aid in decision making. Between January 2015 and July 2016, a total of 977 consecutively seen men underwent multiparametric prostate MRI, and 342 underwent MRI-ultrasound (US) fusion targeted biopsy. A total of 474 lesions were retrospectively reviewed, and 111 were scored as PI-RADS category 3 and were visualized using a 3-T MRI scanner. Multiparametric prostate MR images were prospectively interpreted by body subspecialty radiologists trained to use PI-RADS version 2. CSC was defined as a Gleason score of at least 7 on targeted biopsy. A multivariate logistic regression model was constructed to identify the RFs associated with CSC. Of the 111 PI-RADS category 3 lesions, 81 (73.0%) were benign, 11 (9.9%) were clinically insignificant (Gleason score, 6), and 19 (17.1%) were clinically significant. On multivariate analysis, three RFs were identified as significant predictors of CSC: older patient age (odds ratio [OR], 1.13; p = 0.002), smaller prostate volume (OR, 0.94; p = 0.008), and abnormal digital rectal examination (DRE) findings (OR, 3.92; p = 0.03). For PI-RADS category 3 lesions associated with zero, one, two, or three RFs, the risk of CSC was 4%, 16%, 62%, and 100%, respectively. PI-RADS category 3 lesions for which two or more RFs were noted (e.g., age ≥ 70 years, gland size ≤ 36 mL, or abnormal DRE findings) had a CSC detection rate of 67% with a sensitivity of 53%, a specificity of 95%, a positive predictive value of 67%, and a negative predictive value of 91%. Incorporating clinical parameters into risk stratification algorithms may improve the ability to detect clinically significant disease among PI-RADS category 3 lesions and may aid in the decision to perform biopsy.

TMPRSS4 induces cancer stem cell-like properties in lung cancer cells and correlates with ALDH expression in NSCLC patients.

PubMed

de Aberasturi, Arrate L; Redrado, Miriam; Villalba, Maria; Larzabal, Leyre; Pajares, Maria J; Garcia, Javier; Evans, Stephanie R; Garcia-Ros, David; Bodegas, Maria Elena; Lopez, Lissett; Montuenga, Luis; Calvo, Alfonso

2016-01-28

Metastasis involves a series of changes in cancer cells that promote their escape from the primary tumor and colonization to a new organ. This process is related to the transition from an epithelial to a mesenchymal phenotype (EMT). Recently, some authors have shown that migratory cells with an EMT phenotype share properties of cancer stem cells (CSCs), which allow them to form a new tumor mass. The type II transmembrane serine protease TMPRSS4 is highly expressed in some solid tumors, promotes metastasis and confers EMT features to cancer cells. We hypothesized that TMPRSS4 could also provide CSC properties. Overexpression of TMPRSS4 reduces E-cadherin and induces N-cadherin and vimentin in A549 lung cancer cells, supporting an EMT phenotype. These changes are accompanied by enhanced migration, invasion and tumorigenicity in vivo. TMPRSS4 expression was highly increased in a panel of lung cancer cells cultured as tumorspheres (a typical assay to enrich for CSCs). H358 and H441 cells with knocked-down TMPRSS4 levels were significantly less able to form primary and secondary tumorspheres than control cells. Moreover, they showed a lower proportion of ALDH+ cells (examined by FACS analysis) and lower expression of some CSC markers than controls. A549 cells overexpressing TMPRSS4 conferred the opposite phenotype and were also more sensitive to the CSC-targeted drug salinomycin than control cells, but were more resistant to regular chemotherapeutic drugs (cisplatin, gemcitabine and 5-fluorouracil). Analysis of 70 NSCLC samples from patients revealed a very significant correlation between TMPRSS4 expression and CSC markers ALDH (p = 0.0018) and OCT4 (p = 0.0004), suggesting that TMPRSS4 is associated with a CSC phenotype in patients' tumors. These results show that TMPRSS4, in addition to inducing EMT, can also promote CSC features in lung cancer; therefore, CSC-targeting drugs could be an appropriate treatment for TMPRSS4+ tumors. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Microenvironmental Modulation of Decorin and Lumican in Temozolomide-Resistant Glioblastoma and Neuroblastoma Cancer Stem-Like Cells.

PubMed

Farace, Cristiano; Oliver, Jaime Antonio; Melguizo, Consolacion; Alvarez, Pablo; Bandiera, Pasquale; Rama, Ana Rosa; Malaguarnera, Giulia; Ortiz, Raul; Madeddu, Roberto; Prados, Jose

2015-01-01

The presence of cancer stem cells (CSCs) or tumor-initiating cells can lead to cancer recurrence in a permissive cell-microenvironment interplay, promoting invasion in glioblastoma (GBM) and neuroblastoma (NB). Extracellular matrix (ECM) small leucine-rich proteoglycans (SLRPs) play multiple roles in tissue homeostasis by remodeling the extracellular matrix (ECM) components and modulating intracellular signaling pathways. Due to their pan-inhibitory properties against receptor tyrosine kinases (RTKs), SLRPs are reported to exert anticancer effects in vitro and in vivo. However, their roles seem to be tissue-specific and they are also involved in cancer cell migration and drug resistance, paving the way to complex different scenarios. The aim of this study was to determine whether the SLRPs decorin (DCN) and lumican (LUM) are recruited in cell plasticity and microenvironmental adaptation of differentiated cancer cells induced towards stem-like phenotype. Floating neurospheres were generated by applying CSC enrichment medium (neural stem cell serum-free medium, NSC SFM) to the established SF-268 and SK-N-SH cancer cell lines, cellular models of GBM and NB, respectively. In both models, the time-dependent synergistic activation of DCN and LUM was observed. The highest DCN and LUM mRNA/protein expression was detected after cell exposure to NSC SFM for 8/12 days, considering these cells as SLRP-expressing (SLRP+) CSC-like. Ultrastructural imaging showed the cellular heterogeneity of both the GBM and NB neurospheres and identified the inner living cells. Parental cell lines of both GBM and NB grew only in soft agar + NSC SFM, whereas the secondary neurospheres (originated from SLRP+ t8 CSC-like) showed lower proliferation rates than primary neurospheres. Interestingly, the SLRP+ CSC-like from the GBM and NB neurospheres were resistant to temozolomide (TMZ) at concentrations >750 μM. Our results suggest that GBM and NB CSC-like promote the activation of huge quantities of SLRP in response to CSC enrichment, simultaneously acquiring TMZ resistance, cellular heterogeneity, and a quiescent phenotype, suggesting a novel pivotal role for SLRP in drug resistance and cell plasticity of CSC-like, allowing cell survival and ECM/niche modulation potential.

Microenvironmental Modulation of Decorin and Lumican in Temozolomide-Resistant Glioblastoma and Neuroblastoma Cancer Stem-Like Cells

PubMed Central

Melguizo, Consolacion; Alvarez, Pablo; Bandiera, Pasquale; Rama, Ana Rosa; Malaguarnera, Giulia; Ortiz, Raul; Madeddu, Roberto; Prados, Jose

2015-01-01

The presence of cancer stem cells (CSCs) or tumor-initiating cells can lead to cancer recurrence in a permissive cell–microenvironment interplay, promoting invasion in glioblastoma (GBM) and neuroblastoma (NB). Extracellular matrix (ECM) small leucine-rich proteoglycans (SLRPs) play multiple roles in tissue homeostasis by remodeling the extracellular matrix (ECM) components and modulating intracellular signaling pathways. Due to their pan-inhibitory properties against receptor tyrosine kinases (RTKs), SLRPs are reported to exert anticancer effects in vitro and in vivo. However, their roles seem to be tissue-specific and they are also involved in cancer cell migration and drug resistance, paving the way to complex different scenarios. The aim of this study was to determine whether the SLRPs decorin (DCN) and lumican (LUM) are recruited in cell plasticity and microenvironmental adaptation of differentiated cancer cells induced towards stem-like phenotype. Floating neurospheres were generated by applying CSC enrichment medium (neural stem cell serum-free medium, NSC SFM) to the established SF-268 and SK-N-SH cancer cell lines, cellular models of GBM and NB, respectively. In both models, the time-dependent synergistic activation of DCN and LUM was observed. The highest DCN and LUM mRNA/protein expression was detected after cell exposure to NSC SFM for 8/12 days, considering these cells as SLRP-expressing (SLRP+) CSC-like. Ultrastructural imaging showed the cellular heterogeneity of both the GBM and NB neurospheres and identified the inner living cells. Parental cell lines of both GBM and NB grew only in soft agar + NSC SFM, whereas the secondary neurospheres (originated from SLRP+ t8 CSC-like) showed lower proliferation rates than primary neurospheres. Interestingly, the SLRP+ CSC-like from the GBM and NB neurospheres were resistant to temozolomide (TMZ) at concentrations >750 μM. Our results suggest that GBM and NB CSC-like promote the activation of huge quantities of SLRP in response to CSC enrichment, simultaneously acquiring TMZ resistance, cellular heterogeneity, and a quiescent phenotype, suggesting a novel pivotal role for SLRP in drug resistance and cell plasticity of CSC-like, allowing cell survival and ECM/niche modulation potential. PMID:26230845

Consumer agency in cannabis supply - Exploring auto-regulatory documents of the cannabis social clubs in Spain.

PubMed

Belackova, Vendula; Wilkins, Chris

2018-04-01

There is growing experience with the not-for-profit, consumer-driven cannabis social club (CSC) model that builds on self-supply, self-organization and harm-reduction; these are principles upon which people who use drugs (PWUD) have been engaging for decades. Recent legalization of cannabis in a number of jurisdictions and the related challenges in regulating production, sale, taxation and health-related matters have raised interest in non-commercial models of cannabis supply. The "codes of conduct" (CsoC) of CSC federations in Spain might reveal whether a consumer-based model could overcome these challenges. To examine the content of the CSC auto-regulatory documents, an online search using key terms to identify the CsoC was conducted. Six documents were found; analysis of the main thematic categories and overarching themes was conducted. It was discussed how these corresponded to the areas of cannabis policy regulation and what the main limitations of the CSC model were. The CsoC detailed the rules for CSC administration, not-for-profit aims, "invitation only" and other conditions of membership, collective cultivation and security as well as for operation of the consumption venue and health-related initiatives. The themes in the CsoC overlapped with cannabis regulatory areas as outlined internationally. Concern over cannabis prices and potency was missing in the CsoC. The potential strengths of the CSC model might include safe environment for peer-delivered harm reduction practice, preventing illicit transactions, quality control, shifting economic surplus to the consumers and increased consumer responsibility. The limitations of the CSC model include high threshold, disguised motives, tax revenue and the risk of both under- and over-regulation. CSCs represent an opportunity to enhance consumer agency and responsibility. The right "to be self-supplied" with psychoactive substances can be granted to consumer associations - but authorities need to provide a framework to facilitate this voluntary self-organization, including minimum standards around public health and safety, and to involve consumers in the development of these regulations. Copyright © 2018 Elsevier B.V. All rights reserved.

GENOTOXICITY OF TOBACCO SMOKE AND TOBACCO SMOKE CONDENSATE: A REVIEW

EPA Science Inventory

Genotoxicity of Tobacco Smoke and Tobacco Smoke Condensate: A Review
Abstract
This report reviews the literature on the genotoxicity of main-stream tobacco smoke and cigarette smoke condensate (CSC) published since 1985. CSC is genotoxic in nearly all systems in which it h...

Reprogramming of non-genomic estrogen signaling by the stemness factor SOX2 enhances the tumor-initiating capacity of breast cancer cells.

PubMed

Vazquez-Martin, Alejandro; Cufí, Sílvia; López-Bonet, Eugeni; Corominas-Faja, Bruna; Cuyàs, Elisabet; Vellon, Luciano; Iglesias, Juan Manuel; Leis, Olatz; Martín, Angel G; Menendez, Javier A

2013-11-15

The restoration of pluripotency circuits by the reactivation of endogenous stemness factors, such as SOX2, may provide a new paradigm in cancer development. The tumoral stem cell reprogramming hypothesis, i.e., the ability of stemness factors to redirect normal and differentiated tumor cells toward a less-differentiated and stem-like state, adds new layers of complexity to cancer biology, because the effects of such reprogramming may remain dormant until engaged later in response to (epi)genetic and/or (micro)environmental events. To test this hypothesis, we utilized an in vitro model of a SOX2-overexpressing cancer stem cell (CSC)-like cellular state that was recently developed in our laboratory by employing Yamanaka's nuclear reprogramming technology in the estrogen receptor α (ERα)-positive MCF-7 breast cancer cell line. Despite the acquisition of distinct molecular features that were compatible with a breast CSC-like cellular state, such as strong aldehyde dehydrogenase activity, as detected by ALDEFLUOR, and overexpression of the SSEA-4 and CD44 breast CSC markers, the tumor growth-initiating ability of SOX2-overexpressing CSC-like MCF-7 cells solely occurred in female nude mice supplemented with estradiol when compared with MCF-7 parental cells. Ser118 phosphorylation of estrogen receptor α (ERα), which is a pivotal integrator of the genomic and nongenomic E 2/ERα signaling pathways, drastically accumulated in nuclear speckles in the interphase nuclei of SOX2-driven CSC-like cell populations. Moreover, SOX2-positive CSC-like cells accumulated significantly higher numbers of actively dividing cells, and the highest levels of phospho-Ser118-ERα occurred when chromosomes lined up on a metaphase plate. The previously unrecognized link between E 2/ERα signaling and SOX2-driven stem cell circuitry may significantly impact our current understanding of breast cancer initiation and progression, i.e., SOX2 can promote non-genomic E 2 signaling that leads to nuclear phospho-Ser118-ERα, which ultimately exacerbates genomic ER signaling in response to E 2. Because E 2 stimulation has been recently shown to enhance breast tumor-initiating cell survival by downregulating miR-140, which targets SOX2, the establishment of a bidirectional cross-talk interaction between the stem cell self-renewal regulator, SOX2, and the local and systemic ability of E 2 to increase breast CSC activity may have profound implications for the development of new CSC-directed strategies for breast cancer prevention and therapy.

The FORTRAN static source code analyzer program (SAP) user's guide, revision 1

NASA Technical Reports Server (NTRS)

Decker, W.; Taylor, W.; Eslinger, S.

1982-01-01

The FORTRAN Static Source Code Analyzer Program (SAP) User's Guide (Revision 1) is presented. SAP is a software tool designed to assist Software Engineering Laboratory (SEL) personnel in conducting studies of FORTRAN programs. SAP scans FORTRAN source code and produces reports that present statistics and measures of statements and structures that make up a module. This document is a revision of the previous SAP user's guide, Computer Sciences Corporation document CSC/TM-78/6045. SAP Revision 1 is the result of program modifications to provide several new reports, additional complexity analysis, and recognition of all statements described in the FORTRAN 77 standard. This document provides instructions for operating SAP and contains information useful in interpreting SAP output.

AKT2 siRNA delivery with amphiphilic-based polymeric micelles show efficacy against cancer stem cells.

PubMed

Rafael, Diana; Gener, Petra; Andrade, Fernanda; Seras-Franzoso, Joaquin; Montero, Sara; Fernández, Yolanda; Hidalgo, Manuel; Arango, Diego; Sayós, Joan; Florindo, Helena F; Abasolo, Ibane; Schwartz, Simó; Videira, Mafalda

2018-11-01

Development of RNA interference-based therapies with appropriate therapeutic window remains a challenge for advanced cancers. Because cancer stem cells (CSC) are responsible of sustaining the metastatic spread of the disease to distal organs and the progressive gain of resistance of advanced cancers, new anticancer therapies should be validated specifically for this subpopulation of cells. A new amphihilic-based gene delivery system that combines Pluronic ® F127 micelles with polyplexes spontaneously formed by electrostatic interaction between anionic siRNA and cationic polyethylenimine (PEI) 10K, was designed (PM). Resultant PM gather the requirements for an efficient and safe transport of siRNA in terms of its physicochemical characteristics, internalization capacity, toxicity profile and silencing efficacy. PM were loaded with a siRNA against AKT2, an important oncogene involved in breast cancer tumorigenesis, with a special role in CSC malignancy. Efficacy of siAKT2-PM was validated in CSC isolated from two breast cancer cell lines: MCF-7 and Triple Negative MDA-MB-231 corresponding to an aggressive subtype of breast cancer. In both cases, we observed significant reduction on cell invasion capacity and strong inhibition of mammosphere formation after treatment. These results prompt AKT2 inhibition as a powerful therapeutic target against CSC and pave the way to the appearance of more effective nanomedicine-based gene therapies aimed to prevent CSC-related tumor recurrence.

The Segmental Morphometric Properties of the Horse Cervical Spinal Cord: A Study of Cadaver

PubMed Central

Bahar, Sadullah; Bolat, Durmus; Selcuk, Muhammet Lutfi

2013-01-01

Although the cervical spinal cord (CSC) of the horse has particular importance in diseases of CNS, there is very little information about its segmental morphometry. The objective of the present study was to determine the morphometric features of the CSC segments in the horse and possible relationships among the morphometric features. The segmented CSC from five mature animals was used. Length, weight, diameter, and volume measurements of the segments were performed macroscopically. Lengths and diameters of segments were measured histologically, and area and volume measurements were performed using stereological methods. The length, weight, and volume of the CSC were 61.6 ± 3.2 cm, 107.2 ± 10.4 g, and 95.5 ± 8.3 cm3, respectively. The length of the segments was increased from C 1 to C 3, while it decreased from C 3 to C 8. The gross section (GS), white matter (WM), grey matter (GM), dorsal horn (DH), and ventral horn (VH) had the largest cross-section areas at C 8. The highest volume was found for the total segment and WM at C 4, GM, DH, and VH at C 7, and the central canal (CC) at C 3. The data obtained not only contribute to the knowledge of the normal anatomy of the CSC but may also provide reference data for veterinary pathologists and clinicians. PMID:23476145

Cancer stem-like cell related protein CD166 degrades through E3 ubiquitin ligase CHIP in head and neck cancer.

PubMed

Xiao, Meng; Yan, Ming; Zhang, Jianjun; Xu, Qin; Qi, Shengcai; Wang, Xu; Chen, Wantao

2017-04-01

Our previous studies have identified that CD166 works as a cancer stem-like cell (CSC) marker in epithelial cancers with a large repertoire of cellular functions. However, the post-translational regulatory mechanisms underlying CD166 turnover remain elusive. Several independent studies have reported that E3 ubiquitin ligase CHIP revealed significant biological effects through ubiquitin proteasome pathway on some kinds of malignant tumors. With analyzing the effects of CHIP expressions on stem-like cell populations, we found that CHIP represses CSC characteristics mainly targeting the CSC related protein CD166 in head and neck cancer (HNC). To investigate the role and relationship between CD166 and CHIP, HNC tissues and cell lines were used in this study. A significant negative correlation was observed between the expression levels of CHIP and CD166 in HNC patient samples. We also found that CHIP directly regulates the stability of CD166 protein through the ubiquitin proteasome system, which was also identified participating in the regulation of CSC behaviors in HNCs. Our findings demonstrate that CHIP-CD166-proteasome axis participates in regulating CSC properties in HNCs, suggesting that the regulation of CD166 by CHIP could provide new options for diagnosing and treating in the patients with HNCs. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Reconstruction of radial bone defect in rat by calcium silicate biomaterials.

PubMed

Oryan, Ahmad; Alidadi, Soodeh

2018-05-15

Despite many attempts, an appropriate therapeutic method has not yet been found to enhance bone formation, mechanical strength and structural and functional performances of large bone defects. In the present study, the bone regenerative potential of calcium silicate (CS) biomaterials combined with chitosan (CH) as calcium silicate/chitosan (CSC) scaffold was investigated in a critical radial bone defect in a rat model. The bioimplants were bilaterally implanted in the defects of 20 adult Sprague-Dawley rats. The rats were euthanized and the bone specimens were harvested at the 56th postoperative day. The healed radial bones were evaluated by three-dimensional CT, radiology, histomorphometric analysis, biomechanics, and scanning electron microscopy. The XRD analysis of the CS biomaterial showed its similarity to wollastonite (β-SiCO 3 ). The degradation rate of the CSC scaffold was much higher and it induced milder inflammatory reaction when compared to the CH alone. More bone formation and higher biomechanical performance were observed in the CSC treated group in comparison with the CH treated ones in histological, CT scan and biomechanical examinations. Scanning electron microscopic observation demonstrated the formation of more hydroxyapatite crystals in the defects treated with CSC. This study showed that the CSC biomaterials could be used as proper biodegradable materials in the field of bone reconstruction and tissue engineering. Copyright © 2018 Elsevier Inc. All rights reserved.

Application of stem cells in targeted therapy of breast cancer: a systematic review.

PubMed

Madjd, Zahra; Gheytanchi, Elmira; Erfani, Elham; Asadi-Lari, Mohsen

2013-01-01

The aim of this systematic review was to investigate whether stem cells could be effectively applied in targeted therapy of breast cancer. A systematic literature search was performed for original articles published from January 2007 until May 2012. Nine studies met the inclusion criteria for phase I or II clinical trials, of which three used stem cells as vehicles, two trials used autologous hematopoetic stem cells and in four trials cancer stem cells were targeted. Mesenchymal stem cells (MSCs) were applied as cellular vehicles to transfer therapeutic agents. Cell therapy with MSC can successfully target resistant cancers. Cancer stem cells were selectively targeted via a proteasome-dependent suicide gene leading to tumor regression. Wnt/β-catenin signaling pathway has been also evidenced to be an attractive CSC-target. This systematic review focused on two different concepts of stem cells and breast cancer marking a turning point in the trials that applied stem cells as cellular vehicles for targeted delivery therapy as well as CSC-targeted therapies. Applying stem cells as targeted therapy could be an effective therapeutic approach for treatment of breast cancer in the clinic and in therapeutic marketing; however this needs to be confirmed with further clinical investigations.

Are ovarian cancer stem cells the target for innovative immunotherapy?

PubMed Central

Wang, Liang; Xu, Tianmin; Cui, Manhua

2018-01-01

Cancer stem cells (CSCs), a subpopulation of cancer cells with the ability of self-renewal and differentiation, are believed to be responsible for tumor generation, progression, metastasis, and relapse. Ovarian cancer, the most malignant gynecological cancer, has consistent pathology behavior with CSC model, which suggests that therapies based on ovarian cancer stem cells (OCSCs) can gain a more successful prognosis. Much evidence has proved that epigenetic mechanism played an important role in tumor formation and sustainment. Since CSCs are generally resistant to conventional therapies (chemotherapy and radiotherapy), immunotherapy is a more effective method that has been implemented in the clinic. Chimeric antigen receptor (CAR)-T cell, an adoptive cellular immunotherapy, which results in apparent elimination of tumor in both hematologic and solid cancers, could be used for ovarian cancer. This review covers the basic conception of CSCs and OCSCs, the implication of epigenetic mechanism underlying cancer evolution considering CSC model, the immunotherapies reported for ovarian cancer targeting OCSCs currently, and the relationship between immune system and hierarchy cancer organized by CSCs. Particularly, the promising prospects and potential pitfalls of targeting OCSC surface markers to design CAR-T cellular immunotherapy are discussed here. PMID:29780254

Rebuilding the Campus: A Higher Education Priority for the 21st Century.

ERIC Educational Resources Information Center

Kaiser, Harvey

1989-01-01

The 21st century is within the planning horizon of today's campus decision-makers and government policies. There is currently a heavy demand to fund the reduction of deferred maintenance and make functional program improvements on campuses nationwide. Integrated capital asset management programs for all facilities are essential to success. (MSE)

34 CFR 263.21 - What priority is given to certain projects and applicants?

Code of Federal Regulations, 2014 CFR

2014-07-01

... 34 Education 1 2014-07-01 2014-07-01 false What priority is given to certain projects and... PROGRAMS Demonstration Grants for Indian Children Program § 263.21 What priority is given to certain... subject matters, including math and science, to enable Indian students to successfully transition to...

41 CFR 101-28.306-4 - Expiration or cancellation.

Code of Federal Regulations, 2012 CFR

2012-07-01

... time unless canceled by the Commissioner, FSS, GSA, or by a GSA Regional Administrator. (b) CSC... in organization or accounting structures that might have an impact on their CSC accounts. (d) The... cancellations may be directed by the GSA Regional Administrator in coordination with FSS Central Office. Under...

41 CFR 101-28.306-4 - Expiration or cancellation.

Code of Federal Regulations, 2011 CFR

2011-07-01

... time unless canceled by the Commissioner, FSS, GSA, or by a GSA Regional Administrator. (b) CSC... in organization or accounting structures that might have an impact on their CSC accounts. (d) The... cancellations may be directed by the GSA Regional Administrator in coordination with FSS Central Office. Under...

41 CFR 101-28.306-4 - Expiration or cancellation.

Code of Federal Regulations, 2013 CFR

2013-07-01

... time unless canceled by the Commissioner, FSS, GSA, or by a GSA Regional Administrator. (b) CSC... in organization or accounting structures that might have an impact on their CSC accounts. (d) The... cancellations may be directed by the GSA Regional Administrator in coordination with FSS Central Office. Under...

41 CFR 101-28.306-1 - Establishment of a CSC account by a customer activity.

Code of Federal Regulations, 2013 CFR

2013-07-01

... account by a customer activity. (a) Eligible agencies should contact the GSA Regional Federal Supply... Federal Property Management Regulations System FEDERAL PROPERTY MANAGEMENT REGULATIONS SUPPLY AND... will provide assistance to agencies in the establishment of the CSC account, brief personnel on the use...

41 CFR 101-28.306-1 - Establishment of a CSC account by a customer activity.

Code of Federal Regulations, 2011 CFR

2011-07-01

... account by a customer activity. (a) Eligible agencies should contact the GSA Regional Federal Supply... Federal Property Management Regulations System FEDERAL PROPERTY MANAGEMENT REGULATIONS SUPPLY AND... will provide assistance to agencies in the establishment of the CSC account, brief personnel on the use...

41 CFR 101-28.306-1 - Establishment of a CSC account by a customer activity.

Code of Federal Regulations, 2012 CFR

2012-07-01

... account by a customer activity. (a) Eligible agencies should contact the GSA Regional Federal Supply... Federal Property Management Regulations System FEDERAL PROPERTY MANAGEMENT REGULATIONS SUPPLY AND... will provide assistance to agencies in the establishment of the CSC account, brief personnel on the use...

41 CFR 101-28.306-1 - Establishment of a CSC account by a customer activity.

Code of Federal Regulations, 2010 CFR

2010-07-01

... account by a customer activity. (a) Eligible agencies should contact the GSA Regional Federal Supply... Federal Property Management Regulations System FEDERAL PROPERTY MANAGEMENT REGULATIONS SUPPLY AND... will provide assistance to agencies in the establishment of the CSC account, brief personnel on the use...

41 CFR 101-28.306-1 - Establishment of a CSC account by a customer activity.

Code of Federal Regulations, 2014 CFR

2014-07-01

... account by a customer activity. (a) Eligible agencies should contact the GSA Regional Federal Supply... Federal Property Management Regulations System FEDERAL PROPERTY MANAGEMENT REGULATIONS SUPPLY AND... will provide assistance to agencies in the establishment of the CSC account, brief personnel on the use...

41 CFR 109-28.306 - Customer supply center (CSC) accounts and related controls.

Code of Federal Regulations, 2010 CFR

2010-07-01

... MANAGEMENT REGULATIONS SUPPLY AND PROCUREMENT 28-STORAGE AND DISTRIBUTION 28.3-Customer Supply Centers § 109-28.306 Customer supply center (CSC) accounts and related controls. ... 41 Public Contracts and Property Management 3 2010-07-01 2010-07-01 false Customer supply center...

New Advances and Challenges of Targeting Cancer Stem Cells.

PubMed

Dashzeveg, Nurmaa K; Taftaf, Rokana; Ramos, Erika K; Torre-Healy, Luke; Chumakova, Anastasia; Silver, Daniel J; Alban, Tyler J; Sinyuk, Maksim; Thiagarajan, Praveena S; Jarrar, Awad M; Turaga, Soumya M; Saygin, Caner; Mulkearns-Hubert, Erin; Hitomi, Masahiro; Rich, Jeremy N; Gerson, Stanton L; Lathia, Justin D; Liu, Huiping

2017-10-01

The second International Cancer Stem Cell Conference in Cleveland, Ohio, on September 20-23, 2016, convened 330 attendees from academic, industrial, and clinical organizations. It featured a debate on the concepts and challenges of the cancer stem cells (CSC) as well as CSC-centered scientific sessions on clinical trials, genetics and epigenetics, tumor microenvironment, immune suppression, metastasis, therapeutic resistance, and emerging novel concepts. The conference hosted 35 renowned speakers, 100 posters, 20 short talks, and a preconference workshop. The reported advances of CSC research and therapies fostered new collaborations across national and international borders, and inspired the next generation's young scientists. Cancer Res; 77(19); 5222-7. ©2017 AACR . ©2017 American Association for Cancer Research.

An acceptance-oriented cognitive-behavioral therapy in multimodal rehabilitation: a pre-post test evaluation in highly distressed patients with rheumatic diseases.

PubMed

Vriezekolk, Johanna E; Eijsbouts, Agnes M M; van Lankveld, Wim G J M; Beenackers, Hanneke; Geenen, Rinie; van den Ende, Cornelia H M

2013-06-01

To examine the potential effectiveness of a multimodal rehabilitation program including an acceptance-oriented cognitive-behavioral therapy for highly distressed patients with rheumatic diseases. An observational study employing a one-group pre-post test design (N=25). The primary outcome was psychological distress. Secondary outcomes were quality of life, illness acceptance, and coping flexibility. Group pre-to-post and pre-to-12 months follow-up treatment changes were evaluated by paired-samples t-tests and Cohen's effect sizes (d). Individual changes were evaluated by the reliable change index (RCI) and clinically significant change (CSC) parameters. Significant effects were found post-treatment and maintained at 12 months in psychological distress (d>0.80), illness acceptance (d=1.48) and the SF-36 subscales role physical, vitality, and mental health (d ≥ 0.65). No significant effects were found for coping flexibility and the SF-36 subscales physical functioning, bodily pain, social functioning, and role emotional. Both a reliable (RCI) and clinically significant (CSC) improvement was observed for almost half of the highly distressed patients. The patients enrolled in the multimodal rehabilitation program showed improved psychological health status from pre to post-treatment. A randomized clinical trial is needed to confirm or refute the added value of an acceptance-oriented cognitive-behavioral therapy for highly distressed patients in rehabilitation. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

A Cell Model to Evaluate Chemical Effects on Adult Human Cardiac Progenitor Cell Differentiation and Function

EPA Science Inventory

Adult cardiac stem cells (CSC) and progenitor cells (CPC) represent a population of cells in the heart critical for its regeneration and function over a lifetime. The impact of chemicals on adult human CSC/CPC differentiation and function is unknown. Research was conducted to dev...

Colon Cancer Chemoprevention by Flavonoid Silibinin | Division of Cancer Prevention

Cancer.gov

DESCRIPTION (provided by applicant): Cancer stem cells (CSC) are now recognized as the main cause for initiation, promotion and progression of most of the cancers, including colorectal cancer (CRC). Despite this fact, efficacy of chemopreventive agents towards CSC generation leading to cancer initiation and tumorigenesis has not yet been well- defined. |

Sister M. Madeleva Wolff, C.S.C.

ERIC Educational Resources Information Center

Petit, M. Loretta

2006-01-01

Sister M. Madeleva Wolff, C.S.C., teacher, essayist, poet, and college administrator, through her creative ability and innovative practices made possible major contributions to Catholic education in her lifetime. Without her strong personality and boundless energy, many of her dreams for an ideal college curriculum would not have come to fruition.…

Dynamic Interactions Between Cancer Stem Cells And Their Stromal Partners.

PubMed

Park, Tea Soon; Donnenberg, Vera S; Donnenberg, Albert D; Zambidis, Elias T; Zimmerlin, Ludovic

2014-03-01

The cancer stem cell (CSC) paradigm presumes the existence of self-renewing cancer cells capable of regenerating all tumor compartments and exhibiting stem cell-associated phenotypes. Recent interpretations of the CSC hypothesis envision stemness as a dynamic trait of tumor-initiating cells rather than a defined and unique cell type. Bidirectional crosstalk between the tumor microenvironment and the cancer bulk is well described in the literature and the tumor-associated stroma, vasculature and immune infiltrate have all been implicated as direct contributors to tumor development. These non-neoplastic cell types have also been shown to organize specific niches within the tumor bulk where they can control the intra-tumor CSC content and alter the fate of CSCs and tumor progenitors during tumorigenesis to acquire phenotypic features for invasion, metastasis and dormancy. Despite the complexity of the tumor-stroma interactome, novel therapeutic approaches envision combining tumor-ablative treatment with manipulation of the tumor microenvironment. We will review the currently available literature that provides clues about the complex cellular network that regulate the CSC phenotype and its niches during tumor progression.

Formation of wood secondary cell wall may involve two type cellulose synthase complexes in Populus.

PubMed

Xi, Wang; Song, Dongliang; Sun, Jiayan; Shen, Junhui; Li, Laigeng

2017-03-01

Cellulose biosynthesis is mediated by cellulose synthases (CesAs), which constitute into rosette-like cellulose synthase complexe (CSC) on the plasma membrane. Two types of CSCs in Arabidopsis are believed to be involved in cellulose synthesis in the primary cell wall and secondary cell walls, respectively. In this work, we found that the two type CSCs participated cellulose biosynthesis in differentiating xylem cells undergoing secondary cell wall thickening in Populus. During the cell wall thickening process, expression of one type CSC genes increased while expression of the other type CSC genes decreased. Suppression of different type CSC genes both affected the wall-thickening and disrupted the multilaminar structure of the secondary cell walls. When CesA7A was suppressed, crystalline cellulose content was reduced, which, however, showed an increase when CesA3D was suppressed. The CesA suppression also affected cellulose digestibility of the wood cell walls. The results suggest that two type CSCs are involved in coordinating the cellulose biosynthesis in formation of the multilaminar structure in Populus wood secondary cell walls.

Evaluation and applications of the clinically significant change method with the Violence Risk Scale-Sexual Offender version: implications for risk-change communication.

PubMed

Olver, Mark E; Beggs Christofferson, Sarah M; Wong, Stephen C P

2015-02-01

We examined the use of the clinically significant change (CSC) method with the Violence Risk Scale-Sexual Offender version (VRS-SO), and its implications for risk communication, in a combined sample of 945 treated sexual offenders from three international settings, followed up for a minimum 5 years post-release. The reliable change (RC) index was used to identify thresholds of clinically meaningful change and to create four CSC groups (already okay, recovered, improved, unchanged) based on VRS-SO dynamic scores and amount of change made. Outcome analyses demonstrated important CSC-group differences in 5-year rates of sexual and violent recidivism. However, when baseline risk was controlled via Cox regression survival analysis, the pattern and magnitude of CSC-group differences in sexual and violent recidivism changed to suggest that observed variation in recidivism base rates could be at least partly explained by pre-existing group differences in risk level. Implications for communication of risk-change information and applications to clinical practice are discussed. Copyright © 2015 John Wiley & Sons, Ltd.

Polyhydroxyalkanoate production from sucrose by Cupriavidus necator strains harboring csc genes from Escherichia coli W.

PubMed

Arikawa, Hisashi; Matsumoto, Keiji; Fujiki, Tetsuya

2017-10-01

Cupriavidus necator H16 is the most promising bacterium for industrial production of polyhydroxyalkanoates (PHAs) because of their remarkable ability to accumulate them in the cells. With genetic modifications, this bacterium can produce poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx), which has better physical properties, as well as poly(3-hydroxybutyrate) (PHB) using plant oils and sugars as a carbon source. Considering production cost, sucrose is a very attractive raw material because it is inexpensive; however, this bacterium cannot assimilate sucrose. Here, we used the sucrose utilization (csc) genes of Escherichia coli W to generate C. necator strains that can assimilate sucrose. Especially, glucose-utilizing recombinant C. necator strains harboring the sucrose hydrolase gene (cscA) and sucrose permease gene (cscB) of E. coli W grew well on sucrose as a sole carbon source and accumulated PHB. In addition, strains introduced with a crotonyl-CoA reductase gene (ccr), ethylmalonyl-CoA decarboxylase gene (emd), and some other genetic modifications besides the csc genes and the glucose-utilizing mutations produced PHBHHx with a 3-hydroxyhexanoate (3HHx) content of maximum approximately 27 mol% from sucrose. Furthermore, when one of the PHBHHx-producing strains was cultured with sucrose solution in a fed-batch fermentation, PHBHHx with a 3HHx content of approximately 4 mol% was produced and reached 113 g/L for 65 h, which is approximately 1.5-fold higher than that produced using glucose solution.

An analysis of heat removal during cryogen spray cooling and effects of simultaneous airflow application.

PubMed

Torres, J H; Tunnell, J W; Pikkula, B M; Anvari, B

2001-01-01

Cryogen spray cooling (CSC) is a method used to protect the epidermis from non-specific thermal injury that may occur as a result of various dermatological laser procedures. However, better understanding of cryogen deposition and skin thermal response to CSC is needed to optimize the technique. Temperature measurements and video imaging were carried out on an epoxy phantom as well as human skin during CSC with and without simultaneous application of airflow which was intended to accelerate cryogen evaporation from the substrate surface. An inverse thermal conduction model was used to estimate heat flux and total heat removed. Lifetime of the cryogen film deposited on the surface of skin and epoxy phantom lasted several hundred milliseconds beyond the spurt, but could be reduced to the spurt duration by application of airflow. Values over 100 J/cm(3) were estimated for volumetric heat removed from the epidermis using CSC. "Film cooling" instead of "evaporative cooling" appears to be the dominant mode of CSC on skin. Estimated values of heat removed from the epidermis suggest that a cryogen spurt as long as 200 milliseconds is required to counteract heat generated by high laser fluences (e.g., in treatment of port wine stains) in patients with high concentration of epidermal melanin. Additional cooling beyond spurt termination can be avoided by simultaneous application of airflow, although it is unclear at the moment if avoiding the additional cooling would be beneficial in the actual clinical situation. Copyright 2001 Wiley-Liss, Inc.

The developing cancer stem-cell model: clinical challenges and opportunities.

PubMed

Vermeulen, Louis; de Sousa e Melo, Felipe; Richel, Dick J; Medema, Jan Paul

2012-02-01

During the past decade, a stem-cell-like subset of cancer cells has been identified in many malignancies. These cells, referred to as cancer stem cells (CSCs), are of particular interest because they are believed to be the clonogenic core of the tumour and therefore represent the cell population that drives growth and progression. Many efforts have been made to design therapies that specifically target the CSC population, since this was predicted to be the crucial population to eliminate. However, recent insights have complicated the initial elegant model, by showing a dominant role for the tumour microenvironment in determining CSC characteristics within a malignancy. This is particularly important since dedifferentiation of non-tumorigenic tumour cells towards CSCs can occur, and therefore the CSC population in a neoplasm is expected to vary over time. Moreover, evidence suggests that not all tumours are driven by rare CSCs, but might instead contain a large population of tumorigenic cells. Even though these results suggest that specific targeting of the CSC population might not be a useful therapeutic strategy, research into the hierarchical cellular organisation of malignancies has provided many important new insights in the biology of tumours. In this Personal View, we highlight how the CSC concept is developing and influences our thinking on future treatment for solid tumours, and recommend ways to design clinical trials to assess drugs that target malignant disease in a rational fashion. Copyright © 2012 Elsevier Ltd. All rights reserved.

BORIS up-regulates OCT4 via histone methylation to promote cancer stem cell-like properties in human liver cancer cells.

PubMed

Liu, Qiuying; Chen, Kefei; Liu, Zhongjian; Huang, Yuan; Zhao, Rongce; Wei, Ling; Yu, Xiaoqin; He, Jingyang; Liu, Jun; Qi, Jianguo; Qin, Yang; Li, Bo

2017-09-10

Accumulating evidence has revealed the importance of cancer stem cells (CSCs) in chemoresistance and recurrence. BORIS, a testes-specific CTCF paralog, has been shown to be associated with stemness traits of embryonic cancer cells and epithelial CSCs. We previously reported that BORIS is correlated with the expression of the CSC marker CD90 in hepatocellular carcinoma (HCC). These results encourage us to wonder whether BORIS exerts functions on CSC-like traits of human liver cancer cells. Here, we report that BORIS was enriched in HCC tissues. Exogenous overexpression of BORIS promoted CSC-like properties, including self-renewal, chemoresistance, migration and invasion in Huh7 and HCCLM3 cells. Conversely, BORIS knockdown suppressed CSC-like properties in SMMC-7721 and HepG2 cells and inhibited tumorigenicity in SMMC-7721 cells. Moreover, BORIS alteration did not affect the DNA methylation status of the minimal promoter and exon 1 region of OCT4. However, BORIS overexpression enhanced the amount of BORIS bound on the OCT4 promoter and increased H3K4me2, while reducing H3K27me3; BORIS depletion decreased BORIS and H3K4me2 on the OCT4 promoter, while increasing H3K27me3. These results revealed that BORIS is associated with the CSC-like traits of human liver cancer cells through the epigenetic regulation of OCT4. Copyright © 2017 Elsevier B.V. All rights reserved.

Chemopreventive Effect of PSP Through Targeting of Prostate Cancer Stem Cell-Like Population

PubMed Central

Liu, Ji; Lee, Davy Tak-Wing; Chiu, Yung-Tuen; Ma, Stephanie; Ng, Irene Oi-Lin; Wong, Yong-Chuan; Chan, Franky Leung; Ling, Ming-Tat

2011-01-01

Recent evidence suggested that prostate cancer stem/progenitor cells (CSC) are responsible for cancer initiation as well as disease progression. Unfortunately, conventional therapies are only effective in targeting the more differentiated cancer cells and spare the CSCs. Here, we report that PSP, an active component extracted from the mushroom Turkey tail (also known as Coriolus versicolor), is effective in targeting prostate CSCs. We found that treatment of the prostate cancer cell line PC-3 with PSP led to the down-regulation of CSC markers (CD133 and CD44) in a time and dose-dependent manner. Meanwhile, PSP treatment not only suppressed the ability of PC-3 cells to form prostaspheres under non-adherent culture conditions, but also inhibited their tumorigenicity in vivo, further proving that PSP can suppress prostate CSC properties. To investigate if the anti-CSC effect of PSP may lead to prostate cancer chemoprevention, transgenic mice (TgMAP) that spontaneously develop prostate tumors were orally fed with PSP for 20 weeks. Whereas 100% of the mice that fed with water only developed prostate tumors at the end of experiment, no tumors could be found in any of the mice fed with PSP, suggesting that PSP treatment can completely inhibit prostate tumor formation. Our results not only demonstrated the intriguing anti-CSC effect of PSP, but also revealed, for the first time, the surprising chemopreventive property of oral PSP consumption against prostate cancer. PMID:21603625

Targeting signal transduction pathways of cancer stem cells for therapeutic opportunities of metastasis.

PubMed

Iqbal, Waqas; Alkarim, Saleh; AlHejin, Ahmed; Mukhtar, Hasan; Saini, Kulvinder S

2016-11-15

Tumor comprises of heterogeneous population of cells where not all the disseminated cancer cells have the prerogative and "in-build genetic cues" to form secondary tumors. Cells with stem like properties complemented by key signaling molecules clearly have shown to exhibit selective growth advantage to form tumors at distant metastatic sites. Thus, defining the role of cancer stem cells (CSC) in tumorigenesis and metastasis is emerging as a major thrust area for therapeutic intervention. Precise relationship and regulatory mechanisms operating in various signal transduction pathways during cancer dissemination, extravasation and angiogenesis still remain largely enigmatic. How the crosstalk amongst circulating tumor cells (CTC), epithelial mesenchymal transition (EMT) process and CSC is coordinated for initiating the metastasis at secondary tissues, and during cancer relapse could be of great therapeutic interest. The signal transduction mechanisms facilitating the dissemination, infiltration of CSC into blood stream, extravasations, progression of metastasis phenotype and angiogenesis, at distant organs, are the key pathologically important vulnerabilities being elucidated. Therefore, current new drug discovery focus has shifted towards finding "key driver genes" operating in parallel signaling pathways, during quiescence, survival and maintenance of stemness in CSC. Understanding these mechanisms could open new horizons for tackling the issue of cancer recurrence and metastasis-the cause of ~90% cancer associated mortality. To design futuristic & targeted therapies, we propose a multi-pronged strategy involving small molecules, RNA interference, vaccines, antibodies and other biotechnological modalities against CSC and the metastatic signal transduction cascade.

Finasteride is effective for the treatment of central serous chorioretinopathy

PubMed Central

Moisseiev, E; Holmes, A J; Moshiri, A; Morse, L S

2016-01-01

Purpose To evaluate the safety and efficacy of finasteride treatment in patients with central serous chorioretinopathy (CSC). Methods Retrospective review of 29 eyes of 23 patients who were treated with finasteride for CSC. Previous medical and ocular history, steroid use, length of finasteride treatment, additional treatments for CSC, visual acuity (VA), central macular thickness (CMT), and presence of subretinal fluid (SRF) throughout the follow-up period, and the occurrence of any complications were recorded. Results Initial VA was 0.29±0.31 logMAR, and a trend towards improved VA was noted after 3 months (0.25±0.36 logMAR; P=0.07). VA was significantly improved at the final follow-up (0.23±0.27 logMAR; P=0.024). Initial CMT was 354±160 μm, and was significantly reduced after 1 month of treatment (284±77 μm; P=0.002) and this was maintained to the end of follow-up (247±85 μm; P=0.001). A significant reduction in SRF presence was found at all time points, with an overall 75.9% rate of complete resolution. Following discontinuation, SRF recurrence was noted in 37.5% of cases. No adverse events were recorded. Conclusions Finasteride is a safe and effective treatment for CSC. It may be a possible new option for the initial management of patient with CSC, and a suggested treatment approach is presented. PMID:27055675

Cancer Stem Cells (CSCs) and Mechanisms of Their Regulation: Implications for Cancer Therapy

PubMed Central

Bao, Bin; Ahmad, Aamir; Azmi, Asfar S.; Ali, Shadan; Sarkar, Fazlul H.

2013-01-01

The identification of small subpopulations of cancer stem cells (CSCs) from blood mononuclear cells in human acute myeloid leukemia (AML) in 1997 was the landmark observation for recognizing the potential role of CSCs in tumor aggressiveness. Two critical properties contribute to the functional role of CSCs in the establishment and recurrence of cancerous tumors: their self-renewal capacity and their potential to differentiate into unlimited heterogeneous populations of cancer cells. These findings suggest that CSCs may represent novel therapeutic targets for the treatment and/or prevention of tumor progression as they appear to be involved in cell migration, invasion, metastasis, and treatment resistance, all of which lead to poor clinical outcomes. The identification of CSC-specific markers, the isolation and characterization of CSCs from malignant tissues, and targeting strategies for the destruction of CSCs provides a novel opportunity for cancer research. Described in this overview is the potential implication of several common CSC markers in the identification of CSC subpopulation restricted to common malignant diseases e.g., leukemia, breast, prostate, pancreatic and lung cancers. The role of microRNAs (miRNAs) in the regulation of CSC function is also discussed, as are several methods commonly used in CSC research. The potential role of the anti-diabetic drug metformin that has been shown to have effects on CSCs, and known function as an anti-tumor agent, provides an example of this new class of chemotherapeutics. PMID:23744710

Cytokine-induced killer cells eradicate bone and soft-tissue sarcomas.

PubMed

Sangiolo, Dario; Mesiano, Giulia; Gammaitoni, Loretta; Leuci, Valeria; Todorovic, Maja; Giraudo, Lidia; Cammarata, Cristina; Dell'Aglio, Carmine; D'Ambrosio, Lorenzo; Pisacane, Alberto; Sarotto, Ivana; Miano, Sara; Ferrero, Ivana; Carnevale-Schianca, Fabrizio; Pignochino, Ymera; Sassi, Francesco; Bertotti, Andrea; Piacibello, Wanda; Fagioli, Franca; Aglietta, Massimo; Grignani, Giovanni

2014-01-01

Unresectable metastatic bone sarcoma and soft-tissue sarcomas (STS) are incurable due to the inability to eradicate chemoresistant cancer stem-like cells (sCSC) that are likely responsible for relapses and drug resistance. In this study, we investigated the preclinical activity of patient-derived cytokine-induced killer (CIK) cells against autologous bone sarcoma and STS, including against putative sCSCs. Tumor killing was evaluated both in vitro and within an immunodeficient mouse model of autologous sarcoma. To identify putative sCSCs, autologous bone sarcoma and STS cells were engineered with a CSC detector vector encoding eGFP under the control of the human promoter for OCT4, a stem cell gene activated in putative sCSCs. Using CIK cells expanded from 21 patients, we found that CIK cells efficiently killed allogeneic and autologous sarcoma cells in vitro. Intravenous infusion of CIK cells delayed autologous tumor growth in immunodeficient mice. Further in vivo analyses established that CIK cells could infiltrate tumors and that tumor growth inhibition occurred without an enrichment of sCSCs relative to control-treated animals. These results provide preclinical proof-of-concept for an effective strategy to attack autologous sarcomas, including putative sCSCs, supporting the clinical development of CIK cells as a novel class of immunotherapy for use in settings of untreatable metastatic disease.

Central serous chorioretinopathy fundus autofluorescence comparison with two different confocal scanning laser ophthalmoscopes.

PubMed

Nam, Ki Tae; Yun, Cheol Min; Kim, Jee Taek; Yang, Kyung-Sook; Kim, Hyun Joo; Kim, Seong-Woo; Oh, Jaeryung; Huh, Kuhl

2015-12-01

To compare the lesion characteristics of two different types of confocal scanning laser ophthalmoscopy (cSLO) autofluorescence (AF) images in central serous chorioretinopathy (CSC). The study included 63 eyes of 61 patients; 63 pairs of fundus autofluorescence (FAF) images were compared before CSC resolution in 63 eyes, FAF images of 31 eyes were also compared after CSC resolution. The lesion characteristics (brightness and composite pattern) were compared between Heidelberg Retina Angiograph 2 (HRA2; Heidelberg Engineering, Germany) and Optomap Tx (Optomap; Optos, Scotland) FAF images. The lesion composite pattern was categorized as diffuse or granular. Diffuse AF was defined as homogenously increased or decreased AF, and granular AF was defined as dot-like, coarse changes in AF. The mean disease duration and subretinal fluid (SRF) height in the spectral domain optical coherence tomography were compared according to the FAF image characteristics. Lesion brightness before CSC resolution was hypo-AF in 48 eyes (76.2 %), hyper-AF in three (4.8 %), and mixed-AF in 12 (19.0 %) in HRA2 FAF images. In comparison, nine (14.3 %) images were hypo-AF, 44 (69.8 %) were hyper-AF, and 10 (15.9 %) were mixed-AF in Optomap FAF images (P < 0.0001). There was no significant difference in lesion composite pattern between the two FAF image wavelengths. Patients with lesions that were hyper-AF in Optomap FAF and hypo-AF in HRA2 FAF had a shorter disease duration and greater SRF height (1 month, 281 um) than those who were hyper-AF in both Optomap and HRA2 images (26 months, 153 um; P = 0.004, 0.001). The two types of FAF images of CSC showed different lesion brightness before and after CSC resolution but demonstrated similar lesion composite patterns.

In vitro investigation of head and neck cancer stem cell proportions and their changes following X-ray irradiation as a function of HPV status.

PubMed

Reid, Paul; Wilson, Puthenparampil; Li, Yanrui; Marcu, Loredana G; Staudacher, Alexander H; Brown, Michael P; Bezak, Eva

2017-01-01

Some head and neck squamous cell carcinomas (HNSCC) have a distinct aetiology, which depends on the presence of oncogenic human papilloma virus (HPV). Also, HNSCC contains cancer stem cells (CSCs) that have greater radioresistance and capacity to change replication dynamics in response to irradiation compared to non-clonogenic cells. Since there is limited data on CSCs in HNSCC as a function of HPV status, better understanding of their radiobiology may enable improved treatment outcome. Baseline and post-irradiation changes in CSC proportions were investigated by flow cytometry in a HPV-negative (UM-SCC-1) and a HPV-positive (UM-SCC-47) HNSCC cell line, using fluorescent staining with CD44/ALDH markers. CSC proportions in both irradiated and unirradiated cultures were compared for the two cell lines at various times post-irradiation. To assess repopulation of CSCs, untreated cultures were depleted of CD44+/ALDH+ cells and re-cultured for 3 weeks before flow cytometry analysis. CSC proportions in untreated cell lines were 0.57% (UM-SCC-1) and 2.87% (UM-SCC-47). Untreated cell lines depleted of CD44+/ALDH+ repopulated this phenotype to a mean of 0.15% (UM-SCC-1) and 6.76% (UM-SCC-47). All UM-SCC-47 generations showed elevated CSC proportions after irradiation, with the most significant increase at 2 days post-irradiation. The highest elevation in UM-SCC-1 CSCs was observed at 1 day post-irradiation in the 2nd generation and at 3 days after irradiation in the 3rd generation. When measured after 10 days, only the 3rd generation of UM-SCC-1 showed elevated CSCs. CSC proportions in both cell lines were elevated after exposure and varied with time post irradiation. UM-SCC-47 displayed significant plasticity in repopulating the CSC phenotype in depleted cultures, which was not seen in UM-SCC-1.

Interactive effect of chondroitin sulphate C and hyaluronan on fluid movement across rabbit synovium

PubMed Central

Sabaratnam, S; Coleman, P J; Badrick, E; Mason, R M; Levick, J R

2002-01-01

The polysaccharide hyaluronan (HA) conserves synovial fluid by keeping outflow low and almost constant over a wide pressure range (‘buffering’), but only at concentrations associated with polymer domain overlap. We therefore tested whether polymer interactions can cause buffering, using HA-chondroitin sulphate C (CSC) mixtures. Also, since it has been found that capillary filtration is insensitive to the Starling force interstitial osmotic pressure in frog mesenteries, this was assessed in synovium. Hyaluronan at non-buffering concentrations (0.50–0.75 mg ml−1) and/or 25 mg ml−1 CSC (osmotic pressure 68 cmH2O) was infused into knees of anaesthetised rabbits in vivo. Viscometry and chromatography confirmed that HA interacts with CSC. Pressure (Pj) versus trans-synovial flow (Q̇s) relations were measured. Q̇s was outwards for HA alone (1.2 ± 0.9 μl min−1 at 3 cmH2O, mean ± s.e.m.; n = 6). CSC diffused into synovium and changed Q̇s to filtration at low Pj (−4.1 μl min−1, 3 cmH2O, n = 5, P < 0.02, t test). Filtration ceased upon circulatory arrest (n = 3). At higher Pj, 0.75 mg ml−1 HA plus CSC buffered Q̇s to ∼3 μl min−1 over a wide range of Pj, with an outflow increase of only 0.04 ± 0.02 μl min−1 cmH2O−1 (n = 4). With HA or CSC alone, buffering was absent (slopes 0.57 ± 0.04 μl min−1 cmH2O−1 (n = 4) and 0.86 ± 0.05 μl min−1 cmH2O−1 (n = 5), respectively). Therefore, polymer interactions can cause outflow buffering in joints. Also, interstitial osmotic pressure promoted filtration in fenestrated synovial capillaries, so the results for frog mesentery capillaries cannot be generalised. The difference is attributed to differences in pore ultrastructure. PMID:11927686

Conserving archaeological sites as biological and historical resources in the Gulf of Mexico: the effects of crude oil and dispersant on the biodiversity and corrosion potential of shipwreck bacterial biofilms

NASA Astrophysics Data System (ADS)

Salerno, J. L.; Little, B.; Lee, J.; Ray, R.; Hamdan, L. J.

2016-02-01

There are more than 2,000 documented shipwrecks in the Gulf of Mexico. Historic shipwrecks are invaluable cultural resources, but also serve as artificial reefs, enhancing biodiversity in the deep sea. Oil and gas-related activities have the potential to impact shipwreck sites. An estimated 30% of the oil from the Deepwater Horizon spill was deposited in the deep-sea, in areas that contain shipwrecks. We conducted field and laboratory experiments to determine if crude oil, dispersed oil, and/or dispersant affect the community composition, metabolic function, and/or corrosion potential of microorganisms inhabiting shipwrecks. Platforms containing carbon steel coupons (CSC) (n = 34 per platform) were placed at impacted and non-impacted shipwrecks or into four experimental microcosm tanks. After a 2-week acclimation period, tanks were treated with crude oil and/or dispersant or received no treatment. CSC and seawater (SW) samples for bacterial genetic analysis were collected bi-weekly (at 16 wks for field samples). Proteobacteria dominated field and lab CSC bacterial communities (77-97% of sequences). Field CSC bacterial communities differed at each wreck site (P = 0.001), with oil-impacted sites differing from control sites. Lab CSC bacterial communities differed between all treatment groups (P = 0.005) and changed over the course of the experiment (P = 0.001). CSC bacterial species richness, diversity, and dominance increased with time across all treatments indicating the recruitment and establishment of microbial biofilms on CSCs. SW bacterial communities differed between treatment groups (P = 0.001), with the dispersant treatment being most dissimilar from all other treatments (P < 0.01), and changed over time (P = 0.001). Oil- and oil/dispersant-treated CSCs exhibited higher corrosion compared to dispersant and control treatments. These findings indicate that exposure to oil and/or dispersant may alter bacterial community composition and corrosion potential.

The Chandra Source Catalog 2.0

NASA Astrophysics Data System (ADS)

Evans, Ian N.; Allen, Christopher E.; Anderson, Craig S.; Budynkiewicz, Jamie A.; Burke, Douglas; Chen, Judy C.; Civano, Francesca Maria; D'Abrusco, Raffaele; Doe, Stephen M.; Evans, Janet D.; Fabbiano, Giuseppina; Gibbs, Danny G., II; Glotfelty, Kenny J.; Graessle, Dale E.; Grier, John D.; Hain, Roger; Hall, Diane M.; Harbo, Peter N.; Houck, John C.; Lauer, Jennifer L.; Laurino, Omar; Lee, Nicholas P.; Martínez-Galarza, Juan Rafael; McCollough, Michael L.; McDowell, Jonathan C.; McLaughlin, Warren; Miller, Joseph; Morgan, Douglas L.; Mossman, Amy E.; Nguyen, Dan T.; Nichols, Joy S.; Nowak, Michael A.; Paxson, Charles; Plummer, David A.; Primini, Francis Anthony; Rots, Arnold H.; Siemiginowska, Aneta; Sundheim, Beth A.; Tibbetts, Michael; Van Stone, David W.; Zografou, Panagoula

2018-01-01

The current version of the Chandra Source Catalog (CSC) continues to be well utilized by the astronomical community. Usage over the past year has continued to average more than 15,000 searches per month. Version 1.1 of the CSC, released in 2010, includes properties and data for 158,071 detections, corresponding to 106,586 distinct X-ray sources on the sky. The second major release of the catalog, CSC 2.0, will be made available to the user community in early 2018, and preliminary lists of detections and sources are available now. Release 2.0 will roughly triple the size of the current version of the catalog to an estimated 375,000 detections, corresponding to ~315,000 unique X-ray sources. Compared to release 1.1, the limiting sensitivity for compact sources in CSC 2.0 is significantly enhanced. This improvement is achieved by using a two-stage approach that involves stacking (co-adding) multiple observations of the same field prior to source detection, and then using an improved source detection approach that enables us to detect point source down to ~5 net counts on-axis for exposures shorter than ~15 ks. In addition to enhanced source detection capabilities, improvements to the Bayesian aperture photometry code included in release 2.0 provides robust photometric probability density functions (PDFs) in crowded fields even for low count detections. All post-aperture photometry properties (e.g., hardness ratios, source variability) work directly from the PDFs in release 2.0. CSC 2.0 also adds a Bayesian Blocks analysis of the multi-band aperture photometry PDFs to identify multiple observations of the same source that have similar photometric properties, and therefore can be analyzed simultaneously to improve S/N.We briefly describe these and other updates that significantly enhance the scientific utility of CSC 2.0 when compared to the earlier catalog release.This work has been supported by NASA under contract NAS 8-03060 to the Smithsonian Astrophysical Observatory for operation of the Chandra X-ray Center.

Mechanistic Exploration of Cancer Stem Cell Marker Voltage-Dependent Calcium Channel α2δ1 Subunit-mediated Chemotherapy Resistance in Small-Cell Lung Cancer.

PubMed

Yu, Jiangyong; Wang, Shuhang; Zhao, Wei; Duan, Jianchun; Wang, Zhijie; Chen, Hanxiao; Tian, Yanhua; Wang, Di; Zhao, Jun; An, Tongtong; Bai, Hua; Wu, Meina; Wang, Jie

2018-05-01

Purpose: Chemoresistance in small-cell lung cancer (SCLC) is reportedly attributed to the existence of resistant cancer stem cells (CSC). Studies involving CSC-specific markers and related mechanisms in SCLC remain limited. This study explored the role of the voltage-dependent calcium channel α2δ1 subunit as a CSC marker in chemoresistance of SCLC, and explored the potential mechanisms of α2δ1-mediated chemoresistance and strategies of overcoming the resistance. Experimental Design: α2δ1-positive cells were identified and isolated from SCLC cell lines and patient-derived xenograft (PDX) models, and CSC-like properties were subsequently verified. Transcriptome sequencing and Western blotting were carried out to identify pathways involved in α2δ1-mediated chemoresistance in SCLC. In addition, possible interventions to overcome α2δ1-mediated chemoresistance were examined. Results: Different proportions of α2δ1 + cells were identified in SCLC cell lines and PDX models. α2δ1 + cells exhibited CSC-like properties (self-renewal, tumorigenic, differentiation potential, and high expression of genes related to CSCs and drug resistance). Chemotherapy induced the enrichment of α2δ1 + cells instead of CD133 + cells in PDXs, and an increased proportion of α2δ1 + cells corresponded to increased chemoresistance. Activation and overexpression of ERK in the α2δ1-positive H1048 cell line was identified at the protein level. mAb 1B50-1 was observed to improve the efficacy of chemotherapy and delay relapse as maintenance therapy in PDX models. Conclusions: SCLC cells expressing α2δ1 demonstrated CSC-like properties, and may contribute to chemoresistance. ERK may play a key role in α2δ1-mediated chemoresistance. mAb 1B50-1 may serve as a potential anti-SCLC drug. Clin Cancer Res; 24(9); 2148-58. ©2018 AACR . ©2018 American Association for Cancer Research.

Informing climate change adaptation in the Northeast and Midwest United States: The role of Climate Science Centers

NASA Astrophysics Data System (ADS)

Bryan, A. M.; Morelli, T. L.

2015-12-01

The Department of Interior Northeast Climate Science Center (NE CSC) is part of a federal network of eight Climate Science Centers created to provide scientific information and tools that managers and other parties interested in land, water, wildlife, and cultural resources can use to anticipate, monitor, and adapt to climate change. The NE CSC partners with other federal agencies, universities, and NGOs to facilitate stakeholder interaction and delivery of scientific products. For example, NE CSC researchers have partnered with the National Park Service to help managers at Acadia National Park adapt their infrastructure, operations, and ecosystems to rising seas and more extreme events. In collaboration with the tribal College of Menominee Nation and Michigan State University, the NE CSC is working with indigenous communities in Michigan and Wisconsin to co-develop knowledge of how to preserve their natural and cultural values in the face of climate change. Recently, in its largest collaborative initiative to date, the NE CSC led a cross-institutional effort to produce a comprehensive synthesis of climate change, its impacts on wildlife and their habitats, and available adaptation strategies across the entire Northeast and Midwest region; the resulting document was used by wildlife managers in 22 states to revise their Wildlife Action Plans (WAPs). Additionally, the NE CSC is working with the Wildlife Conservation Society to help inform moose conservation management. Other research efforts include hydrological modeling to inform culvert sizing under greater rainfall intensity, forest and landscape modeling to inform tree planting that mitigates the spread of invasive species, species and habitat modeling to help identify suitable locations for wildlife refugia. In addition, experimental research is being conducted to improve our understanding of how species such as brook trout are responding to climate change. Interacting with stakeholders during all phases of these projects ensures that the science produced meets their specific needs and allows them to make informed decisions to better adapt to our changing climate.

Basal/HER2 breast carcinomas

PubMed Central

Martin-Castillo, Begoña; Oliveras-Ferraros, Cristina; Vazquez-Martin, Alejandro; Cufí, Silvia; Moreno, José Manuel; Corominas-Faja, Bruna; Urruticoechea, Ander; Martín, Ángel G.; López-Bonet, Eugeni; Menendez, Javier A.

2013-01-01

High rates of inherent primary resistance to the humanized monoclonal antibody trastuzumab (Herceptin) are frequent among HER2 gene-amplified breast carcinomas in both metastatic and adjuvant settings. The clinical efficacy of trastuzumab is highly correlated with its ability to specifically and efficiently target HER2-driven populations of breast cancer stem cells (CSCs). Intriguingly, many of the possible mechanisms by which cancer cells escape trastuzumab involve many of the same biomarkers that have been implicated in the biology of CS-like tumor-initiating cells. In the traditional, one-way hierarchy of CSCs in which all cancer cells descend from special self-renewing CSCs, HER2-positive CSCs can occur solely by self-renewal. Therefore, by targeting CSC self-renewal and resistance, trastuzumab is expected to induce tumor shrinkage and further reduce breast cancer recurrence rates when used alongside traditional therapies. In a new, alternate model, more differentiated non-stem cancer cells can revert to trastuzumab-refractory, CS-like cells via the activation of intrinsic or microenvironmental paths-to-stemness, such as the epithelial-to-mesenchymal transition (EMT). Alternatively, stochastic transitions of trastuzumab-responsive CSCs might also give rise to non-CSC cellular states that lack major attributes of CSCs and, therefore, can remain “hidden” from trastuzumab activity. Here, we hypothesize that a better understanding of the CSC/non-CSC social structure within HER2-overexpressing breast carcinomas is critical for trastuzumab-based treatment decisions in the clinic. First, we decipher the biological significance of CSC features and the EMT on the molecular effects and efficacy of trastuzumab in HER2-positive breast cancer cells. Second, we reinterpret the genetic heterogeneity that differentiates trastuzumab-responders from non-responders in terms of CSC cellular states. Finally, we propose that novel predictive approaches aimed at better forecasting early tumor responses to trastuzumab should identify biological determinants that causally underlie the intrinsic flexibility of HER2-positive CSCs to “enter” into or “exit” from trastuzumab-sensitive states. An accurate integration of CSC cellular states and EMT-related biomarkers with the currently available breast cancer molecular taxonomy may significantly improve our ability to make a priori decisions about whether patients belonging to HER2 subtypes differentially enriched with a “mesenchymal transition signature” (e.g., luminal/HER2 vs. basal/HER2) would distinctly benefit from trastuzumab-based therapy ab initio. PMID:23255137

Breast cancer stem cell selectivity of synthetic nanomolar-active salinomycin analogs.

PubMed

Huang, Xiaoli; Borgström, Björn; Kempengren, Sebastian; Persson, Lo; Hegardt, Cecilia; Strand, Daniel; Oredsson, Stina

2016-02-23

Cancer stem cells (CSCs) have been invoked in resistance, recurrence and metastasis of cancer. Consequently, curative cancer treatments may be contingent on CSC selective approaches. Of particular interest in this respect is the ionophore salinomycin, a natural product shown to be 100-fold more active against CSCs than clinically used paclitaxel. We have previously reported that synthetic salinomycin derivatives display increased activity against breast cancer cell lines. Herein we specifically investigate the CSC selectivity of the most active member in each class of C20-O-acylated analogs as well as a C1-methyl ester analog incapable of charge-neutral metal ion transport. JIMT-1 breast cancer cells were treated with three C20-O-acylated analogs, the C1-methyl ester of salinomycin, and salinomycin. The effects of treatment on the CSC-related CD44(+)/CD24(-) and the aldehyde dehydrogenase positive (ALDH(+)) populations were determined using flow cytometry. The survival ability of CSCs after treatment was investigated with a colony formation assay under serum free conditions. The effect of the compounds on cell migration was evaluated using wound-healing and Boyden chamber assays. The expression of vimentin, related to mesenchymal traits and expression of E-cadherin and β-catenin, related to the epithelial traits, were investigated using immunofluorescence microscopy. Treatment with each of the three C20-acylated analogs efficiently decreased the putative CSC population as reflected by reduction of the CD44(+)/CD24(-) and ALDH(+) populations already at a 50 nM concentration. In addition, colony forming efficiency and cell migration were reduced, and the expression of the epithelial markers E-cadherin and β-catenin at the cell surface were increased. In contrast, salinomycin used at the same concentration did not significantly influence the CSC population and the C1-methyl ester was inactive even at a 20 μM concentration. Synthetic structural analogs of salinomycin, previously shown to exhibit increased activity against cancer cells, also exhibited improved activity against CSCs across several assays even at nanomolar concentrations where salinomycin was found inactive. The methyl ester analog of salinomycin, incapable of charge-neutral metal ion transport, did not show activity in CSC assays, lending experimental support to ionophoric stress as the molecular initiating event for the CSC effects of salinomycin and related structures.

The NCC project: A quality management perspective

NASA Technical Reports Server (NTRS)

Lee, Raymond H.

1993-01-01

The Network Control Center (NCC) Project introduced the concept of total quality management (TQM) in mid-1990. The CSC project team established a program which focused on continuous process improvement in software development methodology and consistent deliveries of high quality software products for the NCC. The vision of the TQM program was to produce error free software. Specific goals were established to allow continuing assessment of the progress toward meeting the overall quality objectives. The total quality environment, now a part of the NCC Project culture, has become the foundation for continuous process improvement and has resulted in the consistent delivery of quality software products over the last three years.

The role of autophagy in the cross-talk between epithelial-mesenchymal transitioned tumor cells and cancer stem-like cells.

PubMed

Marcucci, Fabrizio; Ghezzi, Pietro; Rumio, Cristiano

2017-01-30

Epithelial-mesenchymal transition (EMT) and cancer stem-like cells (CSC) are becoming highly relevant targets in anticancer drug discovery. A large body of evidence suggests that epithelial-mesenchymal transitioned tumor cells (EMT tumor cells) and CSCs have similar functions. There is also an overlap regarding the stimuli that can induce the generation of EMT tumor cells and CSCs. Moreover, direct evidence has been brought that EMT can give rise to CSCs. It is unclear however, whether EMT tumor cells should be considered CSCs or if they have to undergo further changes. In this article we summarize available evidence suggesting that, indeed, additional programs must be engaged and we propose that macroautophagy (hereafter, autophagy) represents a key trait distinguishing CSCs from EMT tumor cells. Thus, CSCs have often been reported to be in an autophagic state and blockade of autophagy inhibits CSCs. On the other hand, there is ample evidence showing that EMT and autophagy are distinct events. CSCs, however, represent, by themselves, a heterogeneous population. Thus, CSCs have been distinguished in predominantly non-cycling and cycling CSCs, the latter representing CSCs that self-renew and replenish the pool of differentiated tumor cells. We now suggest that the non-cycling CSC subpopulation is in an autophagic state. We propose also two models to explain the relationship between EMT tumor cells and these two major CSC subpopulations: a branching model in which EMT tumor cells can give rise to cycling or non-cycling CSCs, respectively, and a hierarchical model in which EMT tumor cells are first induced to become autophagic CSCs and, subsequently, cycling CSCs. Finally, we address the therapeutic consequences of these insights.

Four-Year Summary, Educational and Commercial Utilization of a Chemical Information Center, Part II.

ERIC Educational Resources Information Center

Schipma, Peter B., Ed.

The major objective of the Illinois Institute of Technology Retrieval Institute (IITRI) Computer Search Center (CSC) is to educate and link industry, academia, and government institutions to chemical and other scientific information systems and sources. The CSC is in full operation providing services to users from a variety of machine-readable…

Four-Year Summary, Educational and Commercial Utilization of a Chemical Information Center. Part I.

ERIC Educational Resources Information Center

Schipma, Peter B., Ed.

The major objective of the Illinois Institute of Technology (IIT) Computer Search Center (CSC) is to educate and link industry, academia, and government institutions to chemical and other scientific information systems and sources. The CSC is in full operation providing services to users from a variety of machine-readable data bases with minimal…

Final Report. Center for Scalable Application Development Software

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

Mellor-Crummey, John

2014-10-26

The Center for Scalable Application Development Software (CScADS) was established as a part- nership between Rice University, Argonne National Laboratory, University of California Berkeley, University of Tennessee – Knoxville, and University of Wisconsin – Madison. CScADS pursued an integrated set of activities with the aim of increasing the productivity of DOE computational scientists by catalyzing the development of systems software, libraries, compilers, and tools for leadership computing platforms. Principal Center activities were workshops to engage the research community in the challenges of leadership computing, research and development of open-source software, and work with computational scientists to help them develop codesmore » for leadership computing platforms. This final report summarizes CScADS activities at Rice University in these areas.« less

34 CFR 263.21 - What priority is given to certain projects and applicants?

Code of Federal Regulations, 2010 CFR

2010-07-01

... successful entry into school at the kindergarten school level. (2) Early childhood and kindergarten programs... subject matters, including math and science, to enable Indian students to successfully transition to...

The Chandra Source Catalog: Source Variability

NASA Astrophysics Data System (ADS)

Nowak, Michael; Rots, A. H.; McCollough, M. L.; Primini, F. A.; Glotfelty, K. J.; Bonaventura, N. R.; Chen, J. C.; Davis, J. E.; Doe, S. M.; Evans, J. D.; Fabbiano, G.; Galle, E.; Gibbs, D. G.; Grier, J. D.; Hain, R.; Hall, D. M.; Harbo, P. N.; He, X.; Houck, J. C.; Karovska, M.; Lauer, J.; McDowell, J. C.; Miller, J. B.; Mitschang, A. W.; Morgan, D. L.; Nichols, J. S.; Plummer, D. A.; Refsdal, B. L.; Siemiginowska, A. L.; Sundheim, B. A.; Tibbetts, M. S.; Van Stone, D. W.; Winkelman, S. L.; Zografou, P.

2009-01-01

The Chandra Source Catalog (CSC) contains fields of view that have been studied with individual, uninterrupted observations that span integration times ranging from 1 ksec to 160 ksec, and a large number of which have received (multiple) repeat observations days to years later. The CSC thus offers an unprecedented look at the variability of the X-ray sky over a broad range of time scales, and across a wide diversity of variable X-ray sources: stars in the local galactic neighborhood, galactic and extragalactic X-ray binaries, Active Galactic Nuclei, etc. Here we describe the methods used to identify and quantify source variability within a single observation, and the methods used to assess the variability of a source when detected in multiple, individual observations. Three tests are used to detect source variability within a single observation: the Kolmogorov-Smirnov test and its variant, the Kuiper test, and a Bayesian approach originally suggested by Gregory and Loredo. The latter test not only provides an indicator of variability, but is also used to create a best estimate of the variable lightcurve shape. We assess the performance of these tests via simulation of statistically stationary, variable processes with arbitrary input power spectral densities (here we concentrate on results of red noise simulations) at variety of mean count rates and fractional root mean square variabilities relevant to CSC sources. We also assess the false positive rate via simulations of constant sources whose sole source of fluctuation is Poisson noise. We compare these simulations to a preliminary assessment of the variability found in real CSC sources, and estimate the variability sensitivities of the CSC.

The Chandra Source Catalog: Source Variability

NASA Astrophysics Data System (ADS)

Nowak, Michael; Rots, A. H.; McCollough, M. L.; Primini, F. A.; Glotfelty, K. J.; Bonaventura, N. R.; Chen, J. C.; Davis, J. E.; Doe, S. M.; Evans, J. D.; Evans, I.; Fabbiano, G.; Galle, E. C.; Gibbs, D. G., II; Grier, J. D.; Hain, R.; Hall, D. M.; Harbo, P. N.; He, X.; Houck, J. C.; Karovska, M.; Lauer, J.; McDowell, J. C.; Miller, J. B.; Mitschang, A. W.; Morgan, D. L.; Nichols, J. S.; Plummer, D. A.; Refsdal, B. L.; Siemiginowska, A. L.; Sundheim, B. A.; Tibbetts, M. S.; van Stone, D. W.; Winkelman, S. L.; Zografou, P.

2009-09-01

The Chandra Source Catalog (CSC) contains fields of view that have been studied with individual, uninterrupted observations that span integration times ranging from 1 ksec to 160 ksec, and a large number of which have received (multiple) repeat observations days to years later. The CSC thus offers an unprecedented look at the variability of the X-ray sky over a broad range of time scales, and across a wide diversity of variable X-ray sources: stars in the local galactic neighborhood, galactic and extragalactic X-ray binaries, Active Galactic Nuclei, etc. Here we describe the methods used to identify and quantify source variability within a single observation, and the methods used to assess the variability of a source when detected in multiple, individual observations. Three tests are used to detect source variability within a single observation: the Kolmogorov-Smirnov test and its variant, the Kuiper test, and a Bayesian approach originally suggested by Gregory and Loredo. The latter test not only provides an indicator of variability, but is also used to create a best estimate of the variable lightcurve shape. We assess the performance of these tests via simulation of statistically stationary, variable processes with arbitrary input power spectral densities (here we concentrate on results of red noise simulations) at variety of mean count rates and fractional root mean square variabilities relevant to CSC sources. We also assess the false positive rate via simulations of constant sources whose sole source of fluctuation is Poisson noise. We compare these simulations to an assessment of the variability found in real CSC sources, and estimate the variability sensitivities of the CSC.

Ultra-widefield imaging with autofluorescence and indocyanine green angiography in central serous chorioretinopathy.

PubMed

Pang, Claudine E; Shah, Vinnie P; Sarraf, David; Freund, K Bailey

2014-08-01

To describe the spectrum of ultra-widefield autofluorescence (AF) and indocyanine green (ICG) angiographic findings in central serous chorioretinopathy (CSC). Retrospective observational case series. In 37 patients, 65 eyes with CSC from 2 vitreoretinal clinical practices were imaged using ultra-widefield AF and 24 of these eyes with ultra-widefield ICG angiography. Images were correlated with clinical findings and spectral-domain optical coherence tomography (OCT). In 37 (57%) eyes, a variety of altered AF patterns, including gravitational tracts, extended beyond the posterior 50 degrees of retina. Hyper-AF corresponded to areas of subretinal fluid (SRF) on spectral-domain OCT and was found to persist in 44 (70%) eyes for up to 8 years despite resolution of SRF. These areas corresponded to outer retinal atrophy with viable retinal pigment epithelium (RPE) on spectral-domain OCT and may be explained by the unmasking of normal background RPE AF. Ultra-widefield ICG angiography revealed dilated choroidal vessels and choroidal hyperpermeability in areas corresponding to altered AF on ultra-widefield AF in all 24 eyes. In 20 (83.3%) eyes, dilated vessels were observed in association with 1 or more congested vortex veins ampullas, suggesting that outflow congestion may be a contributing factor to the pathogenesis of CSC. Ultra-widefield AF and ICG angiography in CSC revealed more widespread disease in a single image than with standard field imaging and may be useful for identifying peripheral areas of previous or ongoing SRF and choroidal hyperpermeability that can assist in the diagnosis of CSC, surveillance of recurrent disease and treatment of active disease. Copyright © 2014 Elsevier Inc. All rights reserved.

SC-12CD133 SURFACE EXPRESSION INDICATES ASYMMETRIC INHERITANCE OF SIGNALING RECEPTORS DURING GLIOBLASTOMA CANCER STEM CELL MITOSIS

PubMed Central

Hitomi, Masahiro; Jarvis, Stephanie; Yogeswaran, Vid; Pfaff, Kayla; Lathia, Justin

2014-01-01

Asymmetric cell division, the mechanism by which stem cells generate progeny undergoing tissue specific differentiation and a self-renewing stem cell population, enables organogenesis, maintenance of tissue homeostasis, and tissue regeneration without depleting stem cell pools. Cancer stem cells (CSCs) have been identified in malignant cancers including glioblastoma (GBM) by virtue of their enhanced self-renewal capacity and ability to reconstitute an entire tumor with all types of cells found in the original tumor. CSCs also play pivotal roles in therapeutic resistance and are the focus of recent therapeutic development efforts. CSC maintenance is regulated by intrinsic stem cell transcription factors, as well as by multiple extrinsic factors in the tumor microenvironment. In addition to these factors, the mode of cell division plays a critical role in CSC maintenance as exemplified by normal stem cells. Previously, we demonstrated that asymmetric segregation of a CSC marker, CD133, at the time of mitosis correlated with fate determination of CSCs derived from clinical GBM patient samples. Utilizing quantitative immunofluorecsence, we detected that receptors for key signaling molecules critical for CSC maintenance were co-segregated with CD133. Inhibition of downstream signaling induced asymmetric cell death in one of the daughter cells. These data indicate that CD133 marks daughter cells with higher inheritance of molecules that facilitate self-renewal and that asymmetric cell division may benefit CSC survival by concentrating essential receptors to one daughter cell in addition to its potential role in increasing cellular heterogeneity of the tumor.

Canopy structural complexity predicts forest canopy light absorption at continental scales

NASA Astrophysics Data System (ADS)

Atkins, J. W.; Fahey, R. T.; Hardiman, B. S.; Gough, C. M.

2017-12-01

Understanding how the physical structure of forest canopies influence light acquisition is a long-standing area of inquiry fundamental to advancing understanding of many areas of the physical sciences, including the modeling and interpretation of biogeochemical cycles. Conventional measures of forest canopy structure employed in earth system models are often limited to leaf area index (LAI)—a measure of the quantity of leaves in the canopy. However, more novel multi-dimensional measures of canopy structural complexity (CSC) that describe the arrangement of vegetation are now possible because of technological advances, and may improve modeled estimates of canopy light absorption. During 2016 and 2017, we surveyed forests at sites from across the eastern, southern, and midwestern United States using portable canopy LiDAR (PCL). This survey included 14 National Ecological Observation Network (NEON), Long-Term Ecological Research Network (LTER,) Ameriflux, and University affiliated sites. Our findings show that a composite model including CSC parameters and LAI explains 96.8% of the variance in light acquisition, measured as the fraction of photosynthetically absorbed radiation (fPAR) at the continental scale, and improvement of 12% over an LAI only model. Under high light sky conditions, measures of CSC are more strongly coupled with light acquisition than under low light, possibly because light scattering partially decouples CSC from canopy light absorption under low, predominately diffuse light conditions. We conclude that scalable estimates of CSC metrics may improve continent-wide estimates of canopy light absorption and, therefore, carbon uptake, with implications for remote sensing and earth system modeling.

Preschools for Science: The Child Study Centre at the University of British Columbia, 1960-1997

ERIC Educational Resources Information Center

Clark, Penney; Gleason, Mona; Petrina, Stephen

2012-01-01

The development of the Child Study Centre (CSC) at University of British Columbia (UBC) provides a unique perspective on the complex and often contradictory relationship between child study and preschool education in postwar Canada. In this article, the authors detail the development and eventual closure of the CSC at UBC, focusing on the uneasy…

Multi-photon microscopy of tobacco-exposed organotypic skin models

NASA Astrophysics Data System (ADS)

Dao, Belinda; Yamazaki, Alissa; Sun, Chung Ho; Wang, Zifu; Pham, Nguyen; Oldham, Michael; Wong, Brian J. F.

2006-02-01

Cigarette smoking is the most preventable cause of death in the United States. Researchers have extensively studied smoking in regards to its association with cancer, cardiovascular, and pulmonary disease. In contrast, the impact of cigarette smoking on skin has received much less attention. To provide a better understanding of the effect of cigarette smoking on the human dermal layer, this study used multi-photon microscopy (MPM) to examine collagen in organotypic skin models exposed to cigarette smoke condensate (CSC). Adult and neonatal organotypic tissue-engineered artificial skin models (RAFTs) were constructed and exposed to varying concentrations of CSC. Imaging of the RAFTs was performed using MPM and second-harmonic generation signals (SHG), which allowed for collagen structure to be viewed and analyzed as well as for collagen density to be assessed from derived depth-dependent decay (DDD) values. RAFT contraction as related to exposure concentration was monitored as well. Results indicated a dose dependent between contraction rates and CSC concentration. Collagen structure showed more preservation of its original structure at a greater depth in RAFTs with higher concentrations of CSC. No clear trends could be drawn from analysis of derived DDD values.

The p53 Isoform Δ133p53β Promotes Cancer Stem Cell Potential

PubMed Central

Arsic, Nikola; Gadea, Gilles; Lagerqvist, E. Louise; Busson, Muriel; Cahuzac, Nathalie; Brock, Carsten; Hollande, Frederic; Gire, Veronique; Pannequin, Julie; Roux, Pierre

2015-01-01

Summary Cancer stem cells (CSC) are responsible for cancer chemoresistance and metastasis formation. Here we report that Δ133p53β, a TP53 splice variant, enhanced cancer cell stemness in MCF-7 breast cancer cells, while its depletion reduced it. Δ133p53β stimulated the expression of the key pluripotency factors SOX2, OCT3/4, and NANOG. Similarly, in highly metastatic breast cancer cells, aggressiveness was coupled with enhanced CSC potential and Δ133p53β expression. Like in MCF-7 cells, SOX2, OCT3/4, and NANOG expression were positively regulated by Δ133p53β in these cells. Finally, treatment of MCF-7 cells with etoposide, a cytotoxic anti-cancer drug, increased CSC formation and SOX2, OCT3/4, and NANOG expression via Δ133p53, thus potentially increasing the risk of cancer recurrence. Our findings show that Δ133p53β supports CSC potential. Moreover, they indicate that the TP53 gene, which is considered a major tumor suppressor gene, also acts as an oncogene via the Δ133p53β isoform. PMID:25754205

Regulatory role of hexosamine biosynthetic pathway on hepatic cancer stem cell marker CD133 under low glucose conditions

NASA Astrophysics Data System (ADS)

Lin, Shu-Hai; Liu, Tengfei; Ming, Xiaoyan; Tang, Zhi; Fu, Li; Schmitt-Kopplin, Philippe; Kanawati, Basem; Guan, Xin-Yuan; Cai, Zongwei

2016-02-01

Cancer was hypothesized to be driven by cancer stem cells (CSCs), but the metabolic determinants of CSC-like phenotype still remain elusive. Here, we present that hexosamine biosynthetic pathway (HBP) at least in part rescues cancer cell fate with inactivation of glycolysis. Firstly, metabolomic analysis profiled cellular metabolome in CSCs of hepatocellular carcinoma using CD133 cell-surface marker. The metabolic signatures of CD133-positive subpopulation compared to CD133-negative cells highlighted HBP as one of the distinct metabolic pathways, prompting us to uncover the role of HBP in maintenance of CSC-like phenotype. To address this, CSC-like phenotypes and cell survival were investigated in cancer cells under low glucose conditions. As a result, HBP inhibitor azaserine reduced CD133-positive subpopulation and CD133 expression under high glucose condition. Furthermore, treatment of N-Acetylglucosamine in part restores CD133-positive subpopulation when either 2.5 mM glucose in culture media or glycolytic inhibitor 2-deoxy-D-glucose in HCC cell lines was applied, enhancing CD133 expression as well as promoting cancer cell survival. Together, HBP might be a key metabolic determinant in the functions of hepatic CSC marker CD133.

Analytical method validation for the determination of 2,3,3,3-tetrafluoropropene in air samples using gas chromatography with flame ionization detection.

PubMed

Mawn, Michael P; Kurtz, Kristine; Stahl, Deborah; Chalfant, Richard L; Koban, Mary E; Dawson, Barbara J

2013-01-01

A new low global warming refrigerant, 2,3,3,3-tetrafluoro propene, or HFO-1234yf, has been successfully evaluated for automotive air conditioning, and is also being evaluated for stationary refrigeration and air conditioning systems. Due to the advantageous environmental properties of HFO-1234yf versus HFC-134a, coupled with its similar physical properties and system performance, HFO-1234yf is also being evaluated to replace HFC-134a in refrigeration applications where neat HFC-134a is currently used. This study reports on the development and validation of a sampling and analytical method for the determination of HFO-1234yf in air. Different collection media were screened for desorption and simulated sampling efficiency with three-section (350/350/350 mg) Anasorb CSC showing the best results. Therefore, air samples were collected using two 3-section Anasorb CSC sorbent tubes in series at 0.02 L/min for up to 8 hr for sample volumes of up to 9.6 L. The sorbent tubes were extracted in methylene chloride, and analyzed by gas chromatography with flame ionization detection. The method was validated from 0.1× to 20× the target level of 0.5 ppm (2.3 mg/m(3)) for a 9.6 L air volume. Desorption efficiencies for HFO-1234yf were 88 to 109% for all replicates over the validation range with a mean overall recovery of 93%. Simulated sampling efficiencies ranged from 87 to 104% with a mean of 94%. No migration or breakthrough to the back tube was observed under the sampling conditions evaluated. HFO-1234yf samples showed acceptable storage stability on Anasorb CSC sorbent up to a period of 30 days when stored under ambient, refrigerated, or frozen temperature conditions.

Novel strategies for targeting leukemia stem cells: sounding the death knell for blood cancer

PubMed Central

Chavez-Gonzalez, Antonieta; Bakhshinejad, Babak; Pakravan, Katayoon

2018-01-01

Background Cancer stem cells (CSCs), also known as tumor-initiating cells (TICs), are characterized by high self-renewal and multi-lineage differentiation capacities. CSCs are thought to play indispensable roles in the initiation, progression and metastasis of many types of cancer. Leukemias are thought to be initiated and maintained by a specific sub-type of CSC, the leukemia stem cell (LSC). An important feature of LSCs is their resistance to standard therapy, which may lead to relapse. Increasing efforts are aimed at developing novel therapeutic strategies that selectively target LSCs, while sparing their normal counterparts and, thus, minimizing adverse treatment-associated side-effects. These LSC targeting therapies aim to eradicate LSCs through affecting mechanisms that control their survival, self-renewal, differentiation, proliferation and cell cycle progression. Some LSC targeting therapies have already been proven successful in pre-clinical studies and they are now being tested in clinical studies, mainly in combination with conventional treatment regimens. Conclusions A growing body of evidence indicates that the selective targeting of LSCs represents a promising approach to improve disease outcome. Beyond doubt, the CSC hypothesis has added a new dimension to the area of anticancer research, thereby paving the way for shaping a new trend in cancer therapy. PMID:27678246

Systems engineering studies of on-orbit assembly operation

NASA Technical Reports Server (NTRS)

Morgenthaler, George W.

1991-01-01

While the practice of construction has a long history, the underlying theory of construction is relatively young. Very little has been documented as to techniques of logistic support, construction planning, construction scheduling, construction testing, and inspection. The lack of 'systems approaches' to construction processes is certainly one of the most serious roadblocks to the construction of space structures. System engineering research efforts at CSC are aimed at developing concepts and tools which contribute to a systems theory of space construction. The research is also aimed at providing means for trade-offs of design parameters for other research areas in CSC. Systems engineering activity at CSC has divided space construction into the areas of orbital assembly, lunar base construction, interplanetary transport vehicle construction, and Mars base construction. A brief summary of recent results is given. Several models for 'launch-on-time' were developed. Launch-on-time is a critical concept to the assembly of such Earth-orbiting structures as the Space Station Freedom, and to planetary orbiters such as the Mars transfer vehicle. CSC has developed a launch vehicle selection model which uses linear programming to find optimal combinations of launch vehicles of various sizes (Atlas, Titan, Shuttles, HLLV's) to support SEI missions. Recently, the Center developed a cost trade-off model for studying on orbit assembly logistics. With this model it was determined that the most effective size of the HLLV would be in the range of 120 to 200 metric tons to LEO, which is consistent with the choices of General Stafford's Synthesis Group Report. A second-generation Dynamic Construction Activities Model ('DYCAM') process model has been under development, based on our past results in interruptability and our initial DYCAM model. This second-generation model is built on the paradigm of knowledge-based expert systems. It is aimed at providing answers to two questions: (1) what are some necessary or sufficient conditions for judging conceptual designs of spacecraft?, and (2) can a methodology be formulated such that these conditions may be used to provide computer-aided tools for evaluating conceptual designs and planning for space assembly sequences? Early simulation results indicate that the DYCAM model has a clear ability to emulate and simulate human orbital construction processes.

Power Quality Improvement by Unified Power Quality Conditioner Based on CSC Topology Using Synchronous Reference Frame Theory

PubMed Central

Dharmalingam, Rajasekaran; Dash, Subhransu Sekhar; Senthilnathan, Karthikrajan; Mayilvaganan, Arun Bhaskar; Chinnamuthu, Subramani

2014-01-01

This paper deals with the performance of unified power quality conditioner (UPQC) based on current source converter (CSC) topology. UPQC is used to mitigate the power quality problems like harmonics and sag. The shunt and series active filter performs the simultaneous elimination of current and voltage problems. The power fed is linked through common DC link and maintains constant real power exchange. The DC link is connected through the reactor. The real power supply is given by the photovoltaic system for the compensation of power quality problems. The reference current and voltage generation for shunt and series converter is based on phase locked loop and synchronous reference frame theory. The proposed UPQC-CSC design has superior performance for mitigating the power quality problems. PMID:25013854

Power quality improvement by unified power quality conditioner based on CSC topology using synchronous reference frame theory.

PubMed

Dharmalingam, Rajasekaran; Dash, Subhransu Sekhar; Senthilnathan, Karthikrajan; Mayilvaganan, Arun Bhaskar; Chinnamuthu, Subramani

2014-01-01

This paper deals with the performance of unified power quality conditioner (UPQC) based on current source converter (CSC) topology. UPQC is used to mitigate the power quality problems like harmonics and sag. The shunt and series active filter performs the simultaneous elimination of current and voltage problems. The power fed is linked through common DC link and maintains constant real power exchange. The DC link is connected through the reactor. The real power supply is given by the photovoltaic system for the compensation of power quality problems. The reference current and voltage generation for shunt and series converter is based on phase locked loop and synchronous reference frame theory. The proposed UPQC-CSC design has superior performance for mitigating the power quality problems.

Succession planning : determining VDOT's professional needs for the 21st century : final report.

DOT National Transportation Integrated Search

1993-01-01

This report addresses the development of a program of succession planning for the Virginia Department of Transportation (VDOT). Transportation industry findings, confirmed by VDOT demographics, indicate a greater-than- average turnover among senior t...

Metal Oxide/Semiconductor Heterojunctions as Carrier-Selective Contacts for Photovoltaic Applications

NASA Astrophysics Data System (ADS)

Man, Gabriel Jen Shi

Solar radiation is a vast, distributed, and renewable energy source which Humanity can utilize via the photovoltaic effect. The goal of photovoltaic technology is to minimize the true costs, while maximizing the power conversion efficiency and lifetime of the cell/module. Interface-related approaches to achieving this goal are explored here, for two technologically-important classes of light absorbers: crystalline-silicon (c-Si) and metal halide perovskite (MHP). The simplest solar cell consists of a light absorber, sandwiched between two metals with dissimilar work functions. Carrier-selective contacts (CSC's), which are ubiquitous in modern solar cells, are added to improve the electrical performance. Solar cells require asymmetric carrier transport within the cell, which can be effected via electrostatic and/or effective fields, and CSC's augment the asymmetry by selectively transporting holes to one contact, and electrons to the other contact. The proper design and implementation of a CSC is crucial, as the performance, lifetime, and/or cost reduction of a solar cell can be hampered by a single interface or layer. A framework, consisting of eight core requirements, was developed from first-principles to evaluate the effectiveness of a given CSC. The framework includes some requirements which are well-recognized, such as the need for appropriate band offsets, and some requirements which are not well-recognized at the moment, such as the need for effective valence/conduction band density of states matching between the absorber and CSC. The application of the framework to multiple silicon-based and MHP-based CSC's revealed the difficulties of effectively designing and implementing a CSC. A poly(3-hexylthiophene)/c-Si heterojunction was found to be a near ideal hole-selective contact (HSC). Three metal oxide/c-Si heterojunctions initially expected to yield comparable electron-selective contacts (ESC's), titanium dioxide/c-Si (TiO2/c-Si), zinc oxide/c-Si (ZnO/c-Si), and tin dioxide/c-Si (SnO2/c-Si), were instead discovered to be widely different. The TiO2/MHP heterojunction was found to be a moderately ideal ESC, and the nickel oxide/MHP (NiOX/MHP) heterojunction is expected to be a good HSC. If interfacial lead di-iodide (PbI2) is intentionally or unintentionally deposited at the interfaces of a MHP solar cell, it is expected to be detrimental to the operation of the NiOX/MHP HSC, but not to the TiO2/MHP ESC.

From Small Seeds Grow Fruitful Trees: How the PHelpS Peer Help System Stimulated a Diverse and Innovative Research Agenda over 15 Years

ERIC Educational Resources Information Center

Vassileva, J.; McCalla, G. I.; Greer, J. E.

2016-01-01

PHelpS was a system that helped Correctional Service Canada (CSC) workers to find appropriate helpers among their peers when they were encountering problems while interacting with the CSC database. This seemingly simple system had substantial, and surprising, ramifications. Over time it transformed each of our perspectives as to the issues facing…

Harnessing the power of emerging petascale platforms

NASA Astrophysics Data System (ADS)

Mellor-Crummey, John

2007-07-01

As part of the US Department of Energy's Scientific Discovery through Advanced Computing (SciDAC-2) program, science teams are tackling problems that require computational simulation and modeling at the petascale. A grand challenge for computer science is to develop software technology that makes it easier to harness the power of these systems to aid scientific discovery. As part of its activities, the SciDAC-2 Center for Scalable Application Development Software (CScADS) is building open source software tools to support efficient scientific computing on the emerging leadership-class platforms. In this paper, we describe two tools for performance analysis and tuning that are being developed as part of CScADS: a tool for analyzing scalability and performance, and a tool for optimizing loop nests for better node performance. We motivate these tools by showing how they apply to S3D, a turbulent combustion code under development at Sandia National Laboratory. For S3D, our node performance analysis tool helped uncover several performance bottlenecks. Using our loop nest optimization tool, we transformed S3D's most costly loop nest to reduce execution time by a factor of 2.94 for a processor working on a 503 domain.

The effect of adenosine A(2A) receptor antagonists on hydroxyl radical, dopamine, and glutamate in the striatum of rats with altered function of VMAT2.

PubMed

Gołembiowska, Krystyna; Dziubina, Anna

2012-08-01

It has been shown that a decreased vesicular monoamine transporter (VMAT2) function and the disruption of dopamine (DA) storage is an early contributor to oxidative damage of dopamine neurons in Parkinson's disease (PD). In our previous study, we demonstrated that adenosine A(2A) receptor antagonists suppressed oxidative stress in 6-hydroxydopamine-treated rats suggesting that this effect may account for neuroprotective properties of drugs. In the present study, rats were injected with reserpine (10 mg/kg sc) and 18 h later the effect of the adenosine A(2A) receptor antagonists 8-(3-chlorostyryl)caffeine (CSC) and 4-(2-[7-amino-2-(2-furyl)[1,2,4]triazolo[2,3-a][1,3,5]triazin-5-ylamino]ethyl)phenol (ZM 241385) on extracellular DA, glutamate and hydroxyl radical formation was studied in the rat striatum using in vivo microdialysis. By disrupting VMAT2 function, reserpine depleted DA stores, and increased glutamate and hydroxyl radical levels in the rat striatum. CSC (1 mg/kg) but not ZM 241385 (3 mg/kg) increased extracellular DA level and production of hydroxyl radical in reserpinised rats. Both antagonists decreased the reserpine-induced increase in extracellular glutamate. L-3,4-Dihydroxyphenylalanine (L-DOPA) (25 mg/kg) significantly enhanced extracellular DA, had no effect on reserpine-induced hydroxyl radical production and decreased extracellular glutamate concentration. CSC but not ZM 241385 given jointly with L-DOPA increased the effect of L-DOPA on extracellular DA and augmented the reserpine-induced hydroxyl radical production. CSC and ZM 241385 did not influence extracellular glutamate level, which was decreased by L-DOPA. It seems that by decreasing the MAO-dependent DA metabolism rate, CSC raised cytosolic DA and by DA autoxidation, it induced hydroxyl radical overproduction. Thus, the methylxanthine A(2A) receptor antagonists bearing properties of MAO-B inhibitor, like CSC, may cause a risk of oxidative stress resulting from dysfunctional DA storage mechanism in early PD.

The contribution of heavy metals in cigarette smoke condensate to malignant transformation of breast epithelial cells and in vivo initiation of neoplasia through induction of a PI3K-AKT-NFκB cascade.

PubMed

Mohapatra, Purusottam; Preet, Ranjan; Das, Dipon; Satapathy, Shakti Ranjan; Siddharth, Sumit; Choudhuri, Tathagata; Wyatt, Michael D; Kundu, Chanakya Nath

2014-01-01

Cigarette smoking is a crucial factor in the development and progression of multiple cancers including breast. Here, we report that repeated exposure to a fixed, low dose of cigarette smoke condensate (CSC) prepared from Indian cigarettes is capable of transforming normal breast epithelial cells, MCF-10A, and delineate the biochemical basis for cellular transformation. CSC transformed cells (MCF-10A-Tr) were capable of anchorage-independent growth, and their anchorage dependent growth and colony forming ability were higher compared to the non-transformed MCF-10A cells. Increased expression of biomarkers representative of oncogenic transformation (NRP-1, Nectin-4), and anti-apoptotic markers (PI3K, AKT, NFκB) were also noted in the MCF-10A-Tr cells. Short tandem repeat (STR) profiling of MCF-10A and MCF-10A-Tr cells revealed that transformed cells acquired allelic variation during transformation, and had become genetically distinct. MCF-10A-Tr cells formed solid tumors when implanted into the mammary fat pads of Balb/c mice. Data revealed that CSC contained approximately 1.011μg Cd per cigarette equivalent, and Cd (0.0003μg Cd/1×10(7) cells) was also detected in the lysates from MCF-10A cells treated with 25μg/mL CSC. In similar manner to CSC, CdCl2 treatment in MCF-10A cells caused anchorage independent colony growth, higher expression of oncogenic proteins and increased PI3K-AKT-NFκB protein expression. An increase in the expression of PI3K-AKT-NFκB was also noted in the mice xenografts. Interestingly, it was noted that CSC and CdCl2 treatment in MCF-10A cells increased ROS. Collectively, results suggest that heavy metals present in cigarettes of Indian origin may substantially contribute to tumorigenesis by inducing intercellular ROS accumulation and increased expression of PI3K, AKT and NFκB proteins. © 2013.

Enhancement of ethanol production from green liquor-ethanol-pretreated sugarcane bagasse by glucose-xylose cofermentation at high solid loadings with mixed Saccharomyces cerevisiae strains.

PubMed

You, Yanzhi; Li, Pengfei; Lei, Fuhou; Xing, Yang; Jiang, Jianxin

2017-01-01

Efficient cofermentation of glucose and xylose is necessary for economically feasible bioethanol production from lignocellulosic biomass. Here, we demonstrate pretreatment of sugarcane bagasse (SCB) with green liquor (GL) combined with ethanol (GL-Ethanol) by adding different GL amounts. The common Saccharomyces cerevisiae (CSC) and thermophilic S. cerevisiae (TSC) strains were used and different yeast cell mass ratios (CSC to TSC) were compared. The simultaneous saccharification and cofermentation (SSF/SSCF) process was performed by 5-20% (w/v) dry substrate (DS) solid loadings to determine optimal conditions for the co-consumption of glucose and xylose. Compared to previous studies that tested fermentation of glucose using only the CSC, we obtained higher ethanol yield and concentration (92.80% and 23.22 g/L) with 1.5 mL GL/g-DS GL-Ethanol-pretreated SCB at 5% (w/v) solid loading and a CSC-to-TSC yeast cell mass ratio of 1:2 (w/w). Using 10% (w/v) solid loading under the same conditions, the ethanol concentration increased to 42.53 g/L but the ethanol yield decreased to 84.99%. In addition, an increase in the solid loading up to a certain point led to an increase in the ethanol concentration from 1.5 mL GL/g-DS-pretreated SCB. The highest ethanol concentration (68.24 g/L) was obtained with 15% (w/v) solid loading, using a CSC-to-TSC yeast cell mass ratio of 1:3 (w/w). GL-Ethanol pretreatment is a promising pretreatment method for improving both glucan and xylan conversion efficiencies of SCB. There was a competitive relationship between the two yeast strains, and the glucose and xylose utilization ability of the TSC was better than that of the CSC. Ethanol concentration was obviously increased at high solid loading, but the yield decreased as a result of an increase in the viscosity and inhibitor levels in the fermentation system. Finally, the SSCF of GL-Ethanol-pretreated SCB with mixed S. cerevisiae strains increased ethanol concentration and was an effective conversion process for ethanol production at high solid loading.

Flow field measurements in the cell culture unit

NASA Technical Reports Server (NTRS)

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 CSC flow environment are presented and discussed. The final configuration of the CSC employs magnetic stir bars with angled paddles to achieve the necessary flow requirements within the CSC.

Personalized Medicine-Based Approach to Model Patterns of Chemoresistance and Tumor Recurrence Using Ovarian Cancer Stem Cell Spheroids.

PubMed

Raghavan, Shreya; Mehta, Pooja; Ward, Maria R; Bregenzer, Michael E; Fleck, Elyse M A; Tan, Lijun; McLean, Karen; Buckanovich, Ronald J; Mehta, Geeta

2017-11-15

Purpose: Chemoresistant ovarian cancers grow in suspension within the ascites fluid. To screen the effect of chemotherapeutics and biologics on resistant ovarian cancers with a personalized basis, we developed a 3D hanging drop spheroid platform. Experimental Design: We initiated spheroids with primary aldehyde dehydrogenase-positive (ALDH + ) CD133 + ovarian cancer stem cells (OvCSC) from different patient samples and demonstrated that stem cell progeny from harvested spheroids was similar to the primary tumor. OvCSC spheroids were utilized to initiate tumors in immunodeficient mice. Drug responses to cisplatin and ALDH-targeting compound or JAK2 inhibitor determined whether the OvCSC population within the spheroids could be targeted. Cells that escaped therapy were isolated and used to initiate new spheroids and model tumor reemergence in a personalized manner. Results: OvCSC spheroids from different patients exhibited varying and personalized responses to chemotherapeutics. Xenografts were established from OvCSC spheroids, even with a single spheroid. Distinct responses to therapy were observed in distinct primary tumor xenografts similar to those observed in spheroids. Spheroids resistant to cisplatin/ALDH inhibitor therapy had persistent, albeit lower ALDH expression and complete loss of CD133 expression, whereas those resistant to cisplatin/JAK2 inhibitor therapy were enriched for ALDH + cells. Conclusions: Our 3D hanging drop suspension platform can be used to propagate primary OvCSCs that represent individual patient tumors effectively by differentiating in vitro and initiating tumors in mice. Therefore, our platform can be used to study cancer stem cell biology and model tumor reemergence to identify new targeted therapeutics from an effective personalized medicine standpoint. Clin Cancer Res; 23(22); 6934-45. ©2017 AACR . ©2017 American Association for Cancer Research.

Photochemical internalisation, a minimally invasive strategy for light-controlled endosomal escape of cancer stem cell-targeting therapeutics.

PubMed

Selbo, Pål Kristian; Bostad, Monica; Olsen, Cathrine Elisabeth; Edwards, Victoria Tudor; Høgset, Anders; Weyergang, Anette; Berg, Kristian

2015-08-01

Despite progress in radio-, chemo- and photodynamic-therapy (PDT) of cancer, treatment resistance still remains a major problem for patients with aggressive tumours. Cancer stem cells (CSCs) or tumour-initiating cells are intrinsically and notoriously resistant to conventional cancer therapies and are proposed to be responsible for the recurrence of tumours after therapy. According to the CSC hypothesis, it is imperative to develop novel anticancer agents or therapeutic strategies that take into account the biology and role of CSCs. The present review outlines our recent study on photochemical internalisation (PCI) using the clinically relevant photosensitiser TPCS2a/Amphinex® as a rational, non-invasive strategy for the light-controlled endosomal escape of CSC-targeting drugs. PCI is an intracellular drug delivery method based on light-induced ROS-generation and a subsequent membrane-disruption of endocytic vesicles, leading to cytosolic release of the entrapped drugs of interest. In different proof-of-concept studies we have demonstrated that PCI of CSC-directed immunotoxins targeting CD133, CD44, CSPG4 and EpCAM is a highly specific and effective strategy for killing cancer cells and CSCs. CSCs overexpressing CD133 are PDT-resistant; however, this is circumvented by PCI of CD133-targeting immunotoxins. In view of the fact that TPCS2a is not a substrate of the efflux pumps ABCG2 and P-glycoprotein (ABCB1), the PCI-method is a promising anti-CSC therapeutic strategy. Due to a laser-controlled exposure, PCI of CSC-targeting drugs will be confined exclusively to the tumour tissue, suggesting that this drug delivery method has the potential to spare distant normal stem cells.

A possible usage of a CDK4 inhibitor for breast cancer stem cell-targeted therapy

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

Han, Yu Kyeong; Lee, Jae Ho; Park, Ga-Young

2013-01-25

Highlights: ► A CDK4 inhibitor may be used for breast cancer stem cell-targeted therapy. ► The CDK4 inhibitor differentiated the cancer stem cell population (CD24{sup −}/CD44{sup +}) of MDA-MB-231. ► The differentiation of the cancer stem cells by the CDK4 inhibitor radiosensitized MDA-MB-231. -- Abstract: Cancer stem cells (CSCs) are one of the main reasons behind cancer recurrence due to their resistance to conventional anti-cancer therapies. Thus, many efforts are being devoted to developing CSC-targeted therapies to overcome the resistance of CSCs to conventional anti-cancer therapies and decrease cancer recurrence. Differentiation therapy is one potential approach to achieve CSC-targeted therapies.more » This method involves inducing immature cancer cells with stem cell characteristics into more mature or differentiated cancer cells. In this study, we found that a CDK4 inhibitor sensitized MDA-MB-231 cells but not MCF7 cells to irradiation. This difference appeared to be associated with the relative percentage of CSC-population between the two breast cancer cells. The CDK4 inhibitor induced differentiation and reduced the cancer stem cell activity of MDA-MB-231 cells, which are shown by multiple marker or phenotypes of CSCs. Thus, these results suggest that radiosensitization effects may be caused by reducing the CSC-population of MDA-MB-231 through the use of the CDK4 inhibitor. Thus, further investigations into the possible application of the CDK4 inhibitor for CSC-targeted therapy should be performed to enhance the efficacy of radiotherapy for breast cancer.« less

Curcumin and metformin-mediated chemoprevention of oral cancer is associated with inhibition of cancer stem cells.

PubMed

Siddappa, Gangotri; Kulsum, Safeena; Ravindra, Doddathimmasandra Ramanjanappa; Kumar, Vinay V; Raju, Nalini; Raghavan, Nisheena; Sudheendra, Holalugunda Vittalamurthy; Sharma, Anupam; Sunny, Sumsum P; Jacob, Tina; Kuruvilla, Binu T; Benny, Merina; Antony, Benny; Seshadri, Mukund; Lakshminarayan, Padma; Hicks, Wesley; Suresh, Amritha; Kuriakose, Moni A

2017-11-01

Effective chemoprevention is critical for improving outcomes of oral cancer. As single agents, curcumin and metformin are reported to exhibit chemopreventive properties, in vitro as well as in patients with oral cancer. In this study, the chemopreventive efficacy of this drug combination was tested in a 4-nitro quinoline-1-oxide (4NQO) induced mice oral carcinogenesis model. Molecular analysis revealed a cancer stem cell (CSC)-driven oral carcinogenic progression in this model, wherein a progressive increase in the expression of CSC-specific markers (CD44 and CD133) was observed from 8th to 25th week, at transcript (40-100-fold) and protein levels (P ≤ 0.0001). Chemopreventive treatment of the animals at 17th week with curcumin and metformin indicated that the combination regimen decreased tumor volume when compared to the control arm (0.69+0.03 vs 6.66+2.4 mm 3 ; P = 0.04) and improved overall survival of the animals (P = 0.03). Assessment of the molecular status showed an overall downregulation of CSC markers in the treatment arms as compared to the untreated control. Further, in vitro assessment of the treatment on the primary cells generated from progressive stages of 4NQO-induced mice tissue showed a concordant and consistent downregulation of the CSC markers following combination treatment (P < 0.05). The treatment also inhibited the migratory and self-renewal properties of these cells; the effect of which was prominent in the cultures of early dysplastic tissue (P < 0.002). Collectively, our observations suggest that the combination of curcumin and metformin may improve chemopreventive efficacy against oral squamous cell carcinoma through a CSC-associated mechanism. © 2017 Wiley Periodicals, Inc.

Assessment of Grewia oppositifolia leaves as crude protein supplement to low-quality forage diets of sheep.

PubMed

Khan, Nazir Ahmad; Habib, Ghulam

2012-10-01

In the tropical arid and semi-arid regions of many developing countries, sheep are predominantly grazed on low-quality pastures and stall-fed on crop residues. This study evaluated the potential of Grewia oppositifolia tree leaves as crude protein (CP) supplement to the low-quality diets of sheep in comparison with cottonseed cake (CSC). Changes in the chemical composition of the leaves with progressive maturation (December to March) were studied. The leaves maintained a high CP content (>164 g/kg dry matter (DM)) during the prolonged maturation in the winter feed scarcity period. The leaves were rich in Ca (41 g/kg DM) and K (89 g/kg DM). The rate of degradation and effective degradability of CP were consistently higher (P < 0.001) in CSC than in G. oppositifolia. A balance trial in a 4 × 4 Latin square design with four mature Ramghani wethers showed that DM intake, DM and CP digestibility, and N retention did not differ with the substitution of CSC with G. oppositifolia leaves, as a supplement to a basal diet of sorghum hay. Body weight (BW) gain and wool yield responses to the supplements were examined with 36 lambs (27 ± 3 kg BW; age 11 ± 1 months) for 15 weeks. The lambs were only grazed on local pasture (control group) or supplemented with CSC, G. oppositifolia leaves, and their mixture on iso-N basis. Addition of the supplements increased (P < 0.05) BW gain and wool yield, and the leaves were as effective as CSC. These results demonstrated that G. oppositifolia leaves provide good quality green fodder during the prolonged winter feed scarcity period, and that the leaves can be efficiently utilized as a CP supplement to the low-quality diets of sheep.

BRCA1 haploinsufficiency cell-autonomously activates RANKL expression and generates denosumab-responsive breast cancer-initiating cells.

PubMed

Cuyàs, Elisabet; Corominas-Faja, Bruna; Martín, María Muñoz-San; Martin-Castillo, Begoña; Lupu, Ruth; Brunet, Joan; Bosch-Barrera, Joaquim; Menendez, Javier A

2017-05-23

Denosumab, a monoclonal antibody to the receptor activator of nuclear factor-κB ligand (RANKL), might be a novel preventative therapy for BRCA1-mutation carriers at high risk of developing breast cancer. Beyond its well-recognized bone-targeted activity impeding osteoclastogenesis, denosumab has been proposed to interfere with the cross-talk between RANKL-producing sensor cells and cancer-initiating RANK+ responder cells that reside within premalignant tissues of BRCA1-mutation carriers. We herein tested the alternative but not mutually exclusive hypothesis that BRCA1 deficiency might cell-autonomously activate RANKL expression to generate cellular states with cancer stem cell (CSC)-like properties. Using isogenic pairs of normal-like human breast epithelial cells in which the inactivation of a single BRCA1 allele results in genomic instability, we assessed the impact of BRCA1 haploinsufficiency on the expression status of RANK and RANKL. RANK expression remained unaltered but RANKL was dramatically up-regulated in BRCA1mut/+ haploinsufficient cells relative to isogenic BRCA1+/+ parental cells. Neutralizing RANKL with denosumab significantly abrogated the ability of BRCA1 haploinsufficient cells to survive and proliferate as floating microtumors or "mammospheres" under non-adherent/non-differentiating conditions, an accepted surrogate of the relative proportion and survival of CSCs. Intriguingly, CSC-like states driven by epithelial-to-mesenchymal transition or HER2 overexpression traits responded to some extent to denosumab. We propose that breast epithelium-specific mono-allelic inactivation of BRCA1 might suffice to cell-autonomously generate RANKL-addicted, denosumab-responsive CSC-like states. The convergent addiction to a hyperactive RANKL/RANK axis of CSC-like states from genetically diverse breast cancer subtypes might inaugurate a new era of cancer prevention and treatment based on denosumab as a CSC-targeted agent.

The mechanisms for lung cancer risk of PM2.5 : Induction of epithelial-mesenchymal transition and cancer stem cell properties in human non-small cell lung cancer cells.

PubMed

Wei, Hongying; Liang, Fan; Cheng, Wei; Zhou, Ren; Wu, Xiaomeng; Feng, Yan; Wang, Yan

2017-11-01

Fine particulate matter (PM 2.5 ) is a major component of air pollutions that are closely associated with increased risk of lung cancer. However, the role of PM 2.5 in the etiology of lung cancer is largely unknown. In this study, we performed acute (24 hours) and chronic (five passages) exposure models to investigate the carcinogenetic mechanisms of PM 2.5 by targeting the induction of epithelial-mesenchymal transition (EMT) and cancer stem cells (CSC) properties in human non-small cell lung cancer cell line A549. We found that both acute and chronic PM 2.5 exposure enhanced cell migration and invasion, decreased mRNA expression of epithelial markers and increased mRNA expression of mesenchymal markers. Chronic PM 2.5 exposure further induced notable EMT morphology and CSC properties, indicating the developing process of cell malignant behaviors from acute to chronic PM 2.5 exposure. CSC properties induced by chronic PM 2.5 exposure characterized with increased cell-surface markers (CD44, ABCG2), self-renewal genes (SOX2 and OCT4), side population cells and neoplastic capacity. Furthermore, the levels of three stemness-associated microRNAs, Let-7a, miR-16 and miR-34a, were found to be significantly downregulated by chronic PM 2.5 exposure, with microarray data analysis from TCGA database showing their lower expression in human lung adenocarcinoma tissues than that in the adjacent normal lung tissues. These data revealed that the induction of EMT and CSC properties were involved in the lung cancer risk of PM 2.5 , and implicated CSC properties and related microRNAs as possible biomarkers for carcinogenicity prediction of PM 2.5 . © 2017 Wiley Periodicals, Inc.

Assessing the potential of Sun-Induced Fluorescence and the Canopy Scattering Coefficient to track large-scale vegetation dynamics in Amazon forests

NASA Astrophysics Data System (ADS)

Köhler, P.; Guanter, L.; Kobayashi, H.; Walther, S.

2016-12-01

Two new remote sensing vegetation parameters derived from spaceborne spectrometers and simulated with a three dimensional radiative transfer model have been evaluated in terms of their prospects and drawbacks for the monitoring of dense vegetation canopies: (i) sun-induced chlorophyll fluorescence (SIF), a unique signal emitted by photosynthetically active vegetation and (ii) the canopy scattering coefficient (CSC), a vegetation parameter derived along with the directional area scattering factor (DASF) and expected to be particularly sensitive to leaf optical properties. Here, we present the first global data set of DASF/CSC and examine the potential of CSC and SIF for providing complementary information on the controversially discussed vegetation seasonality in the Amazon rainforest. A comparison between near-infrared SIF derived from the Global Ozone Monitoring Experiment-2 (GOME-2) instrument and the Orbiting Carbon Observatory-2 (OCO-2) (overpass time in the morning and noon, respectively) reveals the response of SIF to instantaneous photosynthetically active radiation (PAR) and the response of SIF to changing pigment concentrations ('green-up'). The observed seasonality of SIF largely depends on the satellite overpass time which is due to changing temporal trajectories of (instantaneous) PAR with daytime. Therefore, GOME-2 SIF reaches its seasonal maximum in October and around February, while OCO-2 SIF peaks in February and November. We further examine anisotropic reflectance characteristics with the finding that the hot spot effect significantly impacts observed GOME-2 SIF values. On the contrary, our sensitivity analysis suggests that CSC is highly independent of sun-sensor geometry as well as atmospheric effects. The slight annual variability of CSC shows a seasonal cycle attributable to variations in leaf area and/or the amount of precipitation, rather supporting the 'green-up' hypothesis for periods of less intense precipitation.

A retrospective study of treatment for curative synchronous double primary cancers of the head and neck and the esophagus.

PubMed

Okamoto, Tabito; Katada, Chikatoshi; Komori, Shouko; Yamashita, Keishi; Miyamoto, Shunsuke; Kano, Koichi; Seino, Yutomo; Hosono, Hiroshi; Matsuba, Hiroki; Moriya, Hiromitsu; Sugawara, Mitsuhiro; Azuma, Mizutomo; Ishiyama, Hiromichi; Tanabe, Satoshi; Hayakawa, Kazushige; Koizumi, Wasaburo; Okamoto, Makito; Yamashita, Taku

2018-05-08

Curative synchronous double primary cancers of the head and neck and the esophagus (CSC-HE) are frequently detected, but a standard treatment remains to be established. We studied the clinical course to explore appropriate treatment strategies. We retrospectively studied consecutive 33 patients who had CSC-HE. The disease stage was classified into 4 groups: group A, early head and neck cancer (HNC) and early esophageal cancer (EC); group B, early HNC and advanced EC; group C, advanced HNC and early EC; and group D, advanced HNC and advanced EC. As induction chemotherapy, the patients received 3 courses of TPF therapy (docetaxel 75mg/m 2 on day 1, cisplatin 75mg/m 2 on day 1, and 5-fluorouracil 750mg/m 2 on days 1-5) at 3-week intervals. The clinical courses and treatment outcomes were studied according to the disease stage of CSC-HE. The disease stage of CSC-HE was group A in 1 patient (3%), group B in 9 patients (27.3%), group C in 3 patients (9.1%), and group D in 20 patients (60.6%). The median follow-up was 26months, and the 2-year overall survival rate was 67.4%. In groups A, B, and C, the 2-year overall survival rate was 83.3%. In group D, the 2-year overall survival rate was 62.6%. Ten of 20 patients in group D received induction chemotherapy with TPF, and 6 patients were alive and disease free at the time of this writing. The treatment outcomes of patients with CSC-HE were relatively good. TPF induction chemotherapy might be an effective treatment for patients with advanced HNC and advanced EC. Copyright © 2018. Published by Elsevier B.V.

Characteristics of intraretinal deposits in acute central serous chorioretinopathy.

PubMed

Plateroti, Andrea M; Witmer, Matthew T; Kiss, Szilárd; D'Amico, Donald J

2014-01-01

To describe the temporal and spatial characteristics of intraretinal deposits in patients with acute central serous chorioretinopathy (CSC) using spectral domain optical coherence tomography (OCT). We retrospectively reviewed the medical records of all patients that presented with acute CSC to Weill Cornell Medical College from January 2012 to May 2013. Acute CSC was defined as a diagnosis of CSC within 4 months of the onset of symptoms. Only one eye per patient was included in the study. Each patient was imaged with spectral domain OCT at the initial office visit. The decision to reimage these patients was made by the treating physician. A total of 25 patients (25 eyes; 17 men and eight nonpregnant women) were included in this review. Seven of 25 patients (28%) demonstrated intraretinal deposits within the outer plexiform layer during the initial OCT, with deposits appearing as early as the same day as the onset of symptoms. A total of 25 of 25 patients (100%) demonstrated intraretinal deposits in the outer nuclear layer upon initial (76%) or follow-up OCT, as early as 2 days after the onset of symptoms. A total of 24 of 25 patients (96%) demonstrated deposits in the external limiting membrane upon a follow-up OCT, as early as 7 days from symptoms appearing. A total of 24 of 25 patients (96%) developed intraretinal deposits in the inner segment/outer segment layer upon follow-up OCT, appearing as early as 14 days after symptom onset. At the time of resolution of subretinal fluid, 20 of 25 patients (80%) demonstrated intraretinal deposits. Intraretinal deposits are present in the outer retinal layers in patients with acute CSC, with the deposits appearing progressively deeper within the retina as the condition evolves. Upon resolution of subretinal fluid, the deposits slowly resolve.

Extra-virgin olive oil contains a metabolo-epigenetic inhibitor of cancer stem cells

PubMed Central

Corominas-Faja, Bruna; Cuyàs, Elisabet; Lozano-Sánchez, Jesús; Cufí, Sílvia; Verdura, Sara; Fernández-Arroyo, Salvador; Borrás-Linares, Isabel; Martin-Castillo, Begoña; Martin, Ángel G; Lupu, Ruth; Nonell-Canals, Alfons; Micol, Vicente; Joven, Jorge; Segura-Carretero, Antonio; Menendez, Javier A

2018-01-01

Abstract Targeting tumor-initiating, drug-resistant populations of cancer stem cells (CSC) with phytochemicals is a novel paradigm for cancer prevention and treatment. We herein employed a phenotypic drug discovery approach coupled to mechanism-of-action profiling and target deconvolution to identify phenolic components of extra virgin olive oil (EVOO) capable of suppressing the functional traits of CSC in breast cancer (BC). In vitro screening revealed that the secoiridoid decarboxymethyl oleuropein aglycone (DOA) could selectively target subpopulations of epithelial-like, aldehyde dehydrogenase (ALDH)-positive and mesenchymal-like, CD44+CD24−/low CSC. DOA could potently block the formation of multicellular tumorspheres generated from single-founder stem-like cells in a panel of genetically diverse BC models. Pretreatment of BC populations with noncytotoxic doses of DOA dramatically reduced subsequent tumor-forming capacity in vivo. Mice orthotopically injected with CSC-enriched BC-cell populations pretreated with DOA remained tumor-free for several months. Phenotype microarray-based screening pointed to a synergistic interaction of DOA with the mTOR inhibitor rapamycin and the DNA methyltransferase (DNMT) inhibitor 5-azacytidine. In silico computational studies indicated that DOA binds and inhibits the ATP-binding kinase domain site of mTOR and the S-adenosyl-l-methionine (SAM) cofactor-binding pocket of DNMTs. FRET-based Z-LYTE™ and AlphaScreen-based in vitro assays confirmed the ability of DOA to function as an ATP-competitive mTOR inhibitor and to block the SAM-dependent methylation activity of DNMTs. Our systematic in vitro, in vivo and in silico approaches establish the phenol-conjugated oleoside DOA as a dual mTOR/DNMT inhibitor naturally occurring in EVOO that functionally suppresses CSC-like states responsible for maintaining tumor-initiating cell properties within BC populations. PMID:29452350

Metformin Inhibits Cell Proliferation, Migration and Invasion by Attenuating CSC Function Mediated by Deregulating miRNAs in Pancreatic Cancer Cells

PubMed Central

Bao, Bin; Wang, Zhiwei; Ali, Shadan; Ahmad, Aamir; Azmi, Asfar S.; Sarkar, Sanila H.; Banerjee, Sanjeev; Kong, Dejuan; Li, Yiwei; Thakur, Shivam; Sarkar, Fazlul H.

2013-01-01

Pancreatic cancer is the fourth leading cause of cancer-related deaths in the United States, which is, in part, due to intrinsic (de novo) and extrinsic (acquired) resistance to conventional therapeutics, suggesting that innovative treatment strategies are required for overcoming therapeutic resistance to improve overall survival of patients. Oral administration of metformin in patients with diabetes mellitus has been reported to be associated with reduced risk of pancreatic cancer and that metformin has been reported to kill cancer stem cells (CSC); however, the exact molecular mechanism(s) has not been fully elucidated. In the current study, we examined the effect of metformin on cell proliferation, cell migration and invasion, and self-renewal capacity of CSCs and further assessed the expression of CSC marker genes and microRNAs (miRNA) in human pancreatic cancer cells. We found that metformin significantly decreased cell survival, clonogenicity, wound-healing capacity, sphere-forming capacity (pancreatospheres), and increased disintegration of pancreatospheres in both gemcitabine-sensitive and gemcitabine-resistant pancreatic cancer cells. Metformin also decreased the expression of CSC markers, CD44, EpCAM, EZH2, Notch-1, Nanog and Oct4, and caused reexpression of miRNAs (let-7a, let-7b, miR-26a, miR-101, miR-200b, and miR-200c) that are typically lost in pancreatic cancer and especially in pancreatospheres. We also found that reexpression of miR-26a by transfection led to decreased expression of EZH2 and EpCAM in pancreatic cancer cells. These results clearly suggest that the biologic effects of metformin are mediated through reexpression of miRNAs and decreased expression of CSC-specific genes, suggesting that metformin could be useful for overcoming therapeutic resistance of pancreatic cancer cells. PMID:22086681

Excellence in Radiation Research for the 21st Century (EIRR21): description of an innovative research training program.

PubMed

P'ng, Christine; Ito, Emma; How, Christine; Bezjak, Andrea; Bristow, Rob; Catton, Pam; Fyles, Anthony; Gospodarowicz, Mary; Jaffray, David; Kelley, Shana; Wong, Shun; Liu, Fei-Fei

2012-08-01

To describe and assess an interdisciplinary research training program for graduate students, postdoctoral fellows, and clinical fellows focused on radiation medicine; funded by the Canadian Institutes for Health Research since 2003, the program entitled "Excellence in Radiation Research for the 21st Century" (EIRR21) aims to train the next generation of interdisciplinary radiation medicine researchers. Online surveys evaluating EIRR21 were sent to trainees (n=56), mentors (n=36), and seminar speakers (n=72). Face-to-face interviews were also conducted for trainee liaisons (n=4) and participants in the international exchange program (n=2). Overall response rates ranged from 53% (mentors) to 91% (trainees). EIRR21 was well received by trainees, with the acquisition of several important skills related to their research endeavors. An innovative seminar series, entitled Brainstorm sessions, imparting "extracurricular" knowledge in intellectual property protection, commercialization strategies, and effective communication, was considered to be the most valuable component of the program. Networking with researchers in other disciplines was also facilitated owing to program participation. EIRR21 is an innovative training program that positively impacts the biomedical community and imparts valuable skill sets to foster success for the future generation of radiation medicine researchers. Copyright © 2012 Elsevier Inc. All rights reserved.

Excellence in Radiation Research for the 21st Century (EIRR21): Description of an Innovative Research Training Program

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

P'ng, Christine; Ito, Emma; Ontario Cancer Institute, Toronto, Ontario

2012-08-01

Purpose: To describe and assess an interdisciplinary research training program for graduate students, postdoctoral fellows, and clinical fellows focused on radiation medicine; funded by the Canadian Institutes for Health Research since 2003, the program entitled 'Excellence in Radiation Research for the 21st Century' (EIRR21) aims to train the next generation of interdisciplinary radiation medicine researchers. Methods and Materials: Online surveys evaluating EIRR21 were sent to trainees (n=56), mentors (n=36), and seminar speakers (n=72). Face-to-face interviews were also conducted for trainee liaisons (n=4) and participants in the international exchange program (n=2). Results: Overall response rates ranged from 53% (mentors) to 91%more » (trainees). EIRR21 was well received by trainees, with the acquisition of several important skills related to their research endeavors. An innovative seminar series, entitled Brainstorm sessions, imparting 'extracurricular' knowledge in intellectual property protection, commercialization strategies, and effective communication, was considered to be the most valuable component of the program. Networking with researchers in other disciplines was also facilitated owing to program participation. Conclusions: EIRR21 is an innovative training program that positively impacts the biomedical community and imparts valuable skill sets to foster success for the future generation of radiation medicine researchers.« less

Advances in cancer stem cell targeting: How to strike the evil at its root.

PubMed

Pützer, Brigitte M; Solanki, Manish; Herchenröder, Ottmar

2017-10-01

Cancer progression to metastatic stages is still unmanageable and the promise of effective anti-metastatic therapy remains largely unmet, emphasizing the need to develop novel therapeutics. The special focus here is on cancer stem cells (CSC) as the seed of tumor initiation, epithelial-mesenchymal transition, chemoresistance and, as a consequence, drivers of metastatic dissemination. We report on targeted therapies gearing towards the CSC's internal and membrane-anchored markers using agents such as antibody derivatives, nucleic therapeutics, small molecules and genetic payloads. Another emphasis lies on novel proceedings envisaged to deliver current and prospective therapies to the target sites using newest viral and non-viral vector technologies. In this review, we summarize recent progress and remaining challenges in therapeutic strategies to combat CSC. Copyright © 2017 Elsevier B.V. All rights reserved.

Inhibition of Embryonic Genes to Control Colorectal Cancer Metastasis

DTIC Science & Technology

2014-09-01

14. ABSTRACT Embryonic core transcription factors (TFs), primarily the retrogene NanogP8, are the master regulators of cancer stem cells (CSC) in...core transcription factors (TFs), primarily the retrogene NanogP8, are the master regulators of cancer stem cells (CSC) in human colorectal carcinoma...maintaining the stemness of colorectal carcinoma (CRC) as well as the identification of two different pathways by which NANOG and NANOGP8 control pluripotency

Presentation on systems cluster research

NASA Technical Reports Server (NTRS)

Morgenthaler, George W.

1989-01-01

This viewgraph presentation presents an overview of systems cluster research performed by the Center for Space Construction. The goals of the research are to develop concepts, insights, and models for space construction and to develop systems engineering/analysis curricula for training future aerospace engineers. The following topics are covered: CSC systems analysis/systems engineering (SIMCON) model, CSC systems cluster schedule, system life-cycle, model optimization techniques, publications, cooperative efforts, and sponsored research.

The Chandra Source Catalog: Background Determination and Source Detection

NASA Astrophysics Data System (ADS)

McCollough, Michael; Rots, Arnold; Primini, Francis A.; Evans, Ian N.; Glotfelty, Kenny J.; Hain, Roger; Anderson, Craig S.; Bonaventura, Nina R.; Chen, Judy C.; Davis, John E.; Doe, Stephen M.; Evans, Janet D.; Fabbiano, Giuseppina; Galle, Elizabeth C.; Danny G. Gibbs, II; Grier, John D.; Hall, Diane M.; Harbo, Peter N.; He, Xiang Qun (Helen); Houck, John C.; Karovska, Margarita; Kashyap, Vinay L.; Lauer, Jennifer; McCollough, Michael L.; McDowell, Jonathan C.; Miller, Joseph B.; Mitschang, Arik W.; Morgan, Douglas L.; Mossman, Amy E.; Nichols, Joy S.; Nowak, Michael A.; Plummer, David A.; Refsdal, Brian L.; Siemiginowska, Aneta L.; Sundheim, Beth A.; Tibbetts, Michael S.; van Stone, David W.; Winkelman, Sherry L.; Zografou, Panagoula

2009-09-01

The Chandra Source Catalog (CSC) is a major project in which all of the pointed imaging observations taken by the Chandra X-Ray Observatory are used to generate one of the most extensive X-ray source catalog produced to date. Early in the development of the CSC it was recognized that the ability to estimate local background levels in an automated fashion would be critical for essential CSC tasks such as source detection, photometry, sensitivity estimates, and source characterization. We present a discussion of how such background maps are created directly from the Chandra data and how they are used in source detection. The general background for Chandra observations is rather smoothly varying, containing only low spatial frequency components. However, in the case of ACIS data, a high spatial frequency component is added that is due to the readout streaks of the CCD chips. We discuss how these components can be estimated reliably using the Chandra data and what limitations and caveats should be considered in their use. We will discuss the source detection algorithm used for the CSC and the effects of the background images on the detection results. We will also touch on some the Catalog Inclusion and Quality Assurance criteria applied to the source detection results. This work is supported by NASA contract NAS8-03060 (CXC).

Chandra Source Catalog: Background Determination and Source Detection

NASA Astrophysics Data System (ADS)

McCollough, Michael L.; Rots, A. H.; Primini, F. A.; Evans, I. N.; Glotfelty, K. J.; Hain, R.; Anderson, C. S.; Bonaventura, N. R.; Chen, J. C.; Davis, J. E.; Doe, S. M.; Evans, J. D.; Fabbiano, G.; Galle, E.; Gibbs, D. G.; Grier, J. D.; Hall, D. M.; Harbo, P. N.; He, X.; Houck, J. C.; Karovska, M.; Lauer, J.; McDowell, J. C.; Miller, J. B.; Mitschang, A. W.; Morgan, D. L.; Nichols, J. S.; Nowak, M. A.; Plummer, D. A.; Refsdal, B. L.; Siemiginowska, A. L.; Sundheim, B. A.; Tibbetts, M. S.; Van Stone, D. W.; Winkelman, S. L.; Zografou, P.

2009-01-01

The Chandra Source Catalog (CSC) is a major project in which all of the pointed imaging observations taken by the Chandra X-Ray Observatory will used to generate the most extensive X-ray source catalog produced to date. Early in the development of the CSC it was recognized that the ability to estimate local background levels in an automated fashion would be critical for essential CSC tasks such as source detection, photometry, sensitivity estimates, and source characterization. We present a discussion of how such background maps are created directly from the Chandra data and how they are used in source detection. The general background for Chandra observations is rather smoothly varying, containing only low spatial frequency components. However, in the case of ACIS data, a high spatial frequency component is added that is due to the readout streaks of the CCD chips. We discuss how these components can be estimated reliably using the Chandra data and what limitations and caveats should be considered in their use. We will discuss the source detection algorithm used for the CSC and the effects of the background images on the detection results. We will also touch on some the Catalog Inclusion and Quality Assurance criteria applied to the source detection results. This work is supported by NASA contract NAS8-03060 (CXC).

Alcohol- and light-induced electro-oculographic responses in age-related macular degeneration & central serous chorioretinopathy. alcohol- and light-induced EOG responses in ARMD & CSC.

PubMed

Wu, Kathy H C; Marmor, Michael F

2005-01-01

The non-photic electro-oculographic (EOG) response induced by alcohol has been proposed as an indicator of retinal pigment epithelial (RPE) integrity, and reported to be abnormal in age-related macular degeneration (ARMD). To evaluate this proposal, we have measured the alcohol-EOG as well as the ISCEV-standard EOG in patients with ARMD (n=11 patients, 4 eyes with drusen, 8 eyes with 'dry' and 7 eyes with 'wet' lesions) and central serous chorioretinopathy (CSC, n=11 patients, 7 eyes with active and 6 eyes with inactive lesions), compared with 29 normal controls. We recorded the alcohol-induced EOG response after a single oral administration of ethanol at 160 mg/kg, followed by an ISCEV-standard EOG. Blood alcohol levels were monitored with a breath analyzer. We found that neither the alcohol-EOG nor the light-induced EOG response showed any difference between either ARMD or CSC patients and normal controls. Nor was there difference among eyes of different ARMD or CSC subgroups. In addition, blood alcohol concentrations near the time of the alcohol-EOG peak showed no obvious relationship with peak/baseline ratios. These data suggest that neither the alcohol- nor the light-induced EOG is a sensitive indicator of these diseases.

Aldehyde dehydrogenase 1 isoenzyme expression as a marker of cancer stem cells correlates to histopathological features in head and neck cancer: A meta-analysis

PubMed Central

Cai, Chengxuan; Kaufmann, Andreas M.; Albers, Andreas E.

2017-01-01

There is a lack of predictive biomarkers that can identify patients with head and neck squamous cell carcinoma (HNSCC) who will experience treatment failure and develop drug resistance, recurrence, and metastases. Cancer stem-like cells (CSC) were identified as a subset of cells within the tumor in a variety of solid tumors including HNSCC. CSC are considered the tumor-initiating population responsible for recurrence or metastasis and are associated with therapy resistance. This meta-analysis including fourteen studies with altogether 1258 patients updates and summarizes all relevant data on the impact of ALDH1+ CSC on the prognosis of HNSCC and its association with clinicopathological parameters. ALDH1 expression is highly correlated with tumor differentiation (G3 vs. G1+G2; odds ratio = 2.85. 95% CI: 1.72–4.73, P<0.0001) and decreased overall survival (relative risk = 1.77. 95% CI: 1.41–2.22, P<0.0001) if one out of seven studies was excluded because of heterogeneity. These findings provide insights into the understanding of more aggressive tumor phenotypes and also suggest that the prognostic value provided by HNSCC-subtyping by CSC frequency warrant further clinical investigation. PMID:29112953

Cancer stem cells from human glioblastoma resemble but do not mimic original tumors after in vitro passaging in serum-free media.

PubMed

García-Romero, Noemí; González-Tejedo, Carmen; Carrión-Navarro, Josefa; Esteban-Rubio, Susana; Rackov, Gorjana; Rodríguez-Fanjul, Vanessa; Oliver-De La Cruz, Jorge; Prat-Acín, Ricardo; Peris-Celda, María; Blesa, David; Ramírez-Jiménez, Laura; Sánchez-Gómez, Pilar; Perona, Rosario; Escobedo-Lucea, Carmen; Belda-Iniesta, Cristobal; Ayuso-Sacido, Angel

2016-10-04

Human gliomas harbour cancer stem cells (CSCs) that evolve along the course of the disease, forming highly heterogeneous subpopulations within the tumour mass. These cells possess self-renewal properties and appear to contribute to tumour initiation, metastasis and resistance to therapy. CSC cultures isolated from surgical samples are considered the best preclinical in vitro model for primary human gliomas. However, it is not yet well characterized to which extent their biological and functional properties change during in vitro passaging in the serum-free culture conditions. Here, we demonstrate that our CSC-enriched cultures harboured from one to several CSC clones from the human glioma sample. When xenotransplanted into mouse brain, these cells generated tumours that reproduced at least three different dissemination patterns found in original tumours. Along the passages in culture, CSCs displayed increased expression of stem cell markers, different ratios of chromosomal instability events, and a varied response to drug treatment. Our findings highlight the need for better characterization of CSC-enriched cultures in the context of their evolution in vitro, in order to uncover their full potential as preclinical models in the studies aimed at identifying molecular biomarkers and developing new therapeutic approaches of human gliomas.

Thrombolytic treatment to stroke mimic patients via telestroke.

PubMed

Asaithambi, Ganesh; Castle, Amy L; Sperl, Michael A; Ravichandran, Jayashree; Gupta, Aditi; Ho, Bridget M; Hanson, Sandra K

2017-02-01

The safety and outcomes of intravenous thrombolysis (IVT) to stroke patients via telestroke (TS) is similar to those presenting to stroke centers. Little is known on the accuracy of TS diagnosis among those receiving IVT. We sought to compare the rate of patients receiving IVT with diagnosis of ischemic stroke as opposed to stroke mimic (SM) in our TS network to those who presented to our comprehensive stroke center (CSC). Consecutive patients receiving IVT between August 2014 and June 2015 were identified at our CSC and TS network. We compared rates of SM, post-IVT symptomatic intracerebral hemorrhage (sICH), in-hospital mortality, and discharge destination. We evaluated 131 receiving IVT were included in the analysis. Rates of SM receiving IVT were similar (CSC 12% versus 7% TS, p=0.33). Four stroke patients experienced sICH or in-hospital mortality; neither were found among SM patients. Discharge destination was similar between stroke and SM patients (p=0.9). SM patients had higher diagnoses of migraine (p=0.05) and psychiatric illness (p<0.01). The accuracy of diagnosing stroke in IVT-eligible patients evaluated via TS is similar to evaluations at our CSC. Continued efforts should be made to minimize exposure of SM patients to IVT in both settings. Copyright © 2016 Elsevier B.V. All rights reserved.

Finasteride for Chronic Central Serous Chorioretinopathy

PubMed Central

Forooghian, Farzin; Meleth, Annal D.; Cukras, Catherine; Chew, Emily Y.; Wong, Wai T.; Meyerle, Catherine B.

2010-01-01

Purpose To evaluate the safety and efficacy of finasteride, an inhibitor of dihyroxytestosterone (DHT) synthesis, in the treatment of chronic central serous chorioretinopathy (CSC). Methods Five patients with chronic CSC were prospectively enrolled in this pilot study. Patients were administered finasteride (5mg) daily for 3 months, following which study medication was withheld and patients were observed for 3 months. Main outcome measures included best-corrected visual acuity (BCVA), center-subfield macular thickness and subretinal fluid volume as assessed by optical coherence tomography (OCT). Serum DHT, serum testosterone, and urinary cortisol were also measured. Results There was no change in mean BCVA. Mean center-subfield macular thickness and subretinal fluid volume reached a nadir at 3 months, and rose to levels that were below baseline by 6 months. The changes in both OCT parameters paralleled changes in serum DHT level. In four patients, center-subfield macular thickness and/or subretinal fluid volume increased following discontinuation of finasteride. In the remaining patient, both OCT parameters normalized with finasteride and remained stable when the study medication was discontinued. Conclusion Finasteride may represent a novel medical treatment for chronic CSC. Larger controlled clinical trials are needed to further assess the efficacy of finasteride for the treatment of CSC. Summary Pilot study to evaluate finasteride for treatment of chronic central serous chorioretinopathy suggests efficacy and tolerability. PMID:21273946

The Chandra Source Catalog: Statistical Characterization

NASA Astrophysics Data System (ADS)

Primini, Francis A.; Nowak, M. A.; Houck, J. C.; Davis, J. E.; Glotfelty, K. J.; Karovska, M.; Anderson, C. S.; Bonaventura, N. R.; Chen, J. C.; Doe, S. M.; Evans, I. N.; Evans, J. D.; Fabbiano, G.; Galle, E. C.; Gibbs, D. G., II; Grier, J. D.; Hain, R.; Hall, D. M.; Harbo, P. N.; He, X.; Lauer, J.; McCollough, M. L.; McDowell, J. C.; Miller, J. B.; Mitschang, A. W.; Morgan, D. L.; Nichols, J. S.; Plummer, D. A.; Refsdal, B. L.; Rots, A. H.; Siemiginowska, A. L.; Sundheim, B. A.; Tibbetts, M. S.; van Stone, D. W.; Winkelman, S. L.; Zografou, P.

2009-09-01

The Chandra Source Catalog (CSC) will ultimately contain more than ˜250000 x-ray sources in a total area of ˜1% of the entire sky, using data from ˜10000 separate ACIS and HRC observations of a multitude of different types of x-ray sources (see Evans et al. this conference). In order to maximize the scientific benefit of such a large, heterogeneous dataset, careful characterization of the statistical properties of the catalog, i.e., completeness, sensitivity, false source rate, and accuracy of source properties, is required. Our Characterization efforts include both extensive simulations of blank-sky and point source datasets, and detailed comparisons of CSC results with those of other x-ray and optical catalogs. We present here a summary of our characterization results for CSC Release 1 and preliminary plans for future releases. This work is supported by NASA contract NAS8-03060 (CXC).

ERK/p38 MAPK inhibition reduces radio-resistance to a pulsed proton beam in breast cancer stem cells

NASA Astrophysics Data System (ADS)

Jung, Myung-Hwan; Park, Jeong Chan

2015-10-01

Recent studies have identified highly tumorigenic cells with stem cell-like characteristics, termed cancer stem cells (CSCs) in human cancers. CSCs are resistant to conventional radiotherapy and chemotherapy owing to their high DNA repair ability and oncogene overexpression. However, the mechanisms regulating CSC radio-resistance, particularly proton beam resistance, remain unclear. We isolated CSCs from the breast cancer cell lines MCF-7 and MDA-MB-231, which expressed the characteristic breast CSC membrane protein markers CD44+/CD24-/ low , and irradiated the CSCs with pulsed proton beams. We confirmed that CSCs were resistant to pulsed proton beams and showed that treatment with p38 and ERK inhibitors reduced CSC radio-resistance. Based on these results, BCSC radio-resistance can be reduced during proton beam therapy by co-treatment with ERK1/2 or p38 inhibitors, a novel approach to breast cancer therapy.

Golgi-localized STELLO proteins regulate the assembly and trafficking of cellulose synthase complexes in Arabidopsis.

PubMed

Zhang, Yi; Nikolovski, Nino; Sorieul, Mathias; Vellosillo, Tamara; McFarlane, Heather E; Dupree, Ray; Kesten, Christopher; Schneider, René; Driemeier, Carlos; Lathe, Rahul; Lampugnani, Edwin; Yu, Xiaolan; Ivakov, Alexander; Doblin, Monika S; Mortimer, Jenny C; Brown, Steven P; Persson, Staffan; Dupree, Paul

2016-06-09

As the most abundant biopolymer on Earth, cellulose is a key structural component of the plant cell wall. Cellulose is produced at the plasma membrane by cellulose synthase (CesA) complexes (CSCs), which are assembled in the endomembrane system and trafficked to the plasma membrane. While several proteins that affect CesA activity have been identified, components that regulate CSC assembly and trafficking remain unknown. Here we show that STELLO1 and 2 are Golgi-localized proteins that can interact with CesAs and control cellulose quantity. In the absence of STELLO function, the spatial distribution within the Golgi, secretion and activity of the CSCs are impaired indicating a central role of the STELLO proteins in CSC assembly. Point mutations in the predicted catalytic domains of the STELLO proteins indicate that they are glycosyltransferases facing the Golgi lumen. Hence, we have uncovered proteins that regulate CSC assembly in the plant Golgi apparatus.

ABCB5 maintains melanoma-initiating cells through a pro-inflammatory cytokine signaling circuit

PubMed Central

Wilson, Brian J.; Saab, Karim R.; Ma, Jie; Schatton, Tobias; Pütz, Pablo; Zhan, Qian; Murphy, George F.; Gasser, Martin; Waaga-Gasser, Ana Maria; Frank, Natasha Y.; Frank, Markus H.

2014-01-01

The drug efflux transporter ABCB5 identifies cancer stem-like cells (CSC) in diverse human malignancies, where its expression is associated with clinical disease progression and tumor recurrence. ABCB5 confers therapeutic resistance but other functions in tumorigenesis independent of drug efflux have not been described that might help explain why it is so broadly overexpressed in human cancer. Here we show that in melanoma-initiating cells ABCB5 controls IL-1β secretion which serves to maintain slow-cycling, chemoresistant cells through an IL-1β/IL8/CXCR1 cytokine signaling circuit. This CSC maintenance circuit involved reciprocal paracrine interactions with ABCB5-negative cancer cell populations. ABCB5 blockade induced cellular differentiation, reversed resistance to multiple chemotherapeutic agents, and impaired tumor growth in vivo. Together, our results defined a novel function for ABCB5 in CSC maintenance and tumor growth. PMID:24934811

Can-CSC-GBE: Developing Cost-sensitive Classifier with Gentleboost Ensemble for breast cancer classification using protein amino acids and imbalanced data.

PubMed

Ali, Safdar; Majid, Abdul; Javed, Syed Gibran; Sattar, Mohsin

2016-06-01

Early prediction of breast cancer is important for effective treatment and survival. We developed an effective Cost-Sensitive Classifier with GentleBoost Ensemble (Can-CSC-GBE) for the classification of breast cancer using protein amino acid features. In this work, first, discriminant information of the protein sequences related to breast tissue is extracted. Then, the physicochemical properties hydrophobicity and hydrophilicity of amino acids are employed to generate molecule descriptors in different feature spaces. For comparison, we obtained results by combining Cost-Sensitive learning with conventional ensemble of AdaBoostM1 and Bagging. The proposed Can-CSC-GBE system has effectively reduced the misclassification costs and thereby improved the overall classification performance. Our novel approach has highlighted promising results as compared to the state-of-the-art ensemble approaches. Copyright © 2016 Elsevier Ltd. All rights reserved.

The contribution of heavy metals in cigarette smoke condensate to malignant transformation of breast epithelial cells and in vivo initiation of neoplasia through induction of a PI3K–AKT–NFκB cascade

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

Mohapatra, Purusottam; Preet, Ranjan; Das, Dipon

Cigarette smoking is a crucial factor in the development and progression of multiple cancers including breast. Here, we report that repeated exposure to a fixed, low dose of cigarette smoke condensate (CSC) prepared from Indian cigarettes is capable of transforming normal breast epithelial cells, MCF-10A, and delineate the biochemical basis for cellular transformation. CSC transformed cells (MCF-10A-Tr) were capable of anchorage-independent growth, and their anchorage dependent growth and colony forming ability were higher compared to the non-transformed MCF-10A cells. Increased expression of biomarkers representative of oncogenic transformation (NRP-1, Nectin-4), and anti-apoptotic markers (PI3K, AKT, NFκB) were also noted in themore » MCF-10A-Tr cells. Short tandem repeat (STR) profiling of MCF-10A and MCF-10A-Tr cells revealed that transformed cells acquired allelic variation during transformation, and had become genetically distinct. MCF-10A-Tr cells formed solid tumors when implanted into the mammary fat pads of Balb/c mice. Data revealed that CSC contained approximately 1.011 μg Cd per cigarette equivalent, and Cd (0.0003 μg Cd/1 × 10{sup 7} cells) was also detected in the lysates from MCF-10A cells treated with 25 μg/mL CSC. In similar manner to CSC, CdCl{sub 2} treatment in MCF-10A cells caused anchorage independent colony growth, higher expression of oncogenic proteins and increased PI3K–AKT–NFκB protein expression. An increase in the expression of PI3K–AKT–NFκB was also noted in the mice xenografts. Interestingly, it was noted that CSC and CdCl{sub 2} treatment in MCF-10A cells increased ROS. Collectively, results suggest that heavy metals present in cigarettes of Indian origin may substantially contribute to tumorigenesis by inducing intercellular ROS accumulation and increased expression of PI3K, AKT and NFκB proteins. - Highlights: • Repeated exposure of CSC causes malignant transformation in MCF-10A. • MCF-10A-Tr cells showed a distinct STR profile and tumor inducing characteristics. • Increased expression of PI3K, AKT, and NFκB protein in MCF-10A-Tr and solid tumor. • Increased ROS and PI3K-AKT-NFκB proteins in smoke carcinogen exposed MCF-10A cells. • Cadmium may be a strong contributor to the transformation of MCF-10A cells.« less

[Wood smoke condensate induced epithelial-mesenchymal transition in human airway epithelial cells].

PubMed

Li, Wenxi; Zou, Weifeng; Li, Bing; Ran, Pixin

2014-01-01

To observe the detrimental effects of wood smoke condensate (WSC) exposure on human bronchial epithelial cells (HBEC), and to explore the expression of epithelial-mesenchymal transition (EMT) markers in HBEC exposed to WSC. HBEC were exposed respectively to 5, 10, 20, 40 and 50 mg/L of WSC /CSC for 7 days, with control groups only in cell culture medium at the same time, then the total cytoactivity was detected by cell counting kit-8. After observing the cellular morphology of WSC-stimulated HBEC. Western blot and immunofluorescence method were used to evaluate the expression levels of type I collagen, vimentin, E-cad and MMP-9 in HBEC exposed to WSC (10 mg/L) and cigarette smoke condensate (CSC) (10 mg/L) for 7 days. Statistical evaluation of the continuous data was performed by ANOVA. Independent-Samples t-test for between-group comparisons. After 7 days of exposure to WSC, HBEC manifested a morphological characteristic of loss of cell-cell contact and elongated shape. The level of E-cad was decreased in WSC exposure groups (Western blot: 0.30 ± 0.05, F = 22.07, P < 0.05) compared with the groups without WSC exposure (Western blot: 0.59 ± 0.08, F = 22.07, P < 0.05). In contrast, an upregulation in expression of type I collagen (Western blot: 0.58 ± 0.04 vs 0.26 ± 0.02, F = 119.72, P < 0.05) and MMP-9 (0.56 ± 0.08 vs 0.19 ± 0.03, F = 21.79, P < 0.05) was observed in the presence of WSC, compared with the control groups. Immunofluorescence analysis showed that after a 7-day exposure to WSC in these cells, the E-cad protein was lost whereas type I collagen, vimentin and MMP-9 were acquired. Both Western blot and immunofluorescence analysis showed no difference in expression levels of E-cad, type I collagen, vimentin and MMP-9 between WSC and CSC exposure groups. WSC exposure could induce EMT-like process in human airway epithelial cells.

A transferable sucrose utilization approach for non-sucrose-utilizing Escherichia coli strains.

PubMed

Bruschi, Michele; Boyes, Simon J; Sugiarto, Haryadi; Nielsen, Lars K; Vickers, Claudia E

2012-01-01

Sucrose has economic and environmental advantages over glucose as a feedstock for bioprocesses. E. coli is widely used in industry, but the majority of current industrial E. coli strains cannot utilize sucrose. Previous attempts to transfer sucrose catabolic capabilities into non-sucrose-utilizing strains have met with limited success due to low growth rates on sucrose and phenotypic instability of the engineered strains. To address these problems, we developed a transferrable sucrose utilization cassette which confers efficient sucrose catabolism when integrated onto the E. coli chromosome. The cassette was based on the csc genes from E. coli W, a strain which grows very quickly on sucrose. Both plasmid-borne expression and chromosomal integration of a repressor-less sucrose utilizing cassette were investigated in E. coli strains K-12, B and C. In contrast to previous studies, strains harboring chromosomal cassettes could grow at the same rate as they do on glucose. Interestingly, we also discovered that spontaneous chromosomal integration of the csc genes was required to allow efficient growth from plasmid-transformed strains. The ability to engineer industrial strains for efficient sucrose utilization will allow substitution of sucrose for glucose in industrial fermentations. This will encourage the use of sucrose as a carbon source and assist in transition of our petrochemical-based economy to a bio-based economy. Crown Copyright © 2011. Published by Elsevier Inc. All rights reserved.

Ginsenoside-Rb1 targets chemotherapy-resistant ovarian cancer stem cells via simultaneous inhibition of Wnt/β-catenin signaling and epithelial-to-mesenchymal transition

PubMed Central

Deng, Shan; Wong, Chris Kong Chu; Lai, Hung-Cheng; Wong, Alice Sze Tsai

2017-01-01

Chemoresistance is a major clinical problem compromising the successful treatment of cancer. One exciting approach is the eradication of cancer stem/tumor-initiating cells (jointly CSCs), which account for tumor initiation, progression, and drug resistance. Here we show for the first time, with mechanism-based evidence, that ginsenoside-Rb1, a natural saponin isolated from the rhizome of Panax quinquefolius and notoginseng, exhibits potent cytotoxicity on CSCs. Rb1 and its metabolite compound K could effectively suppress CSC self-renewal without regrowth. Rb1 and compound K treatment also sensitized the CSCs to clinically relevant doses of cisplatin and paclitaxel. These effects were associated with the Wnt/β-catenin signaling pathway by downregulating β-catenin/T-cell factor-dependent transcription and expression of its target genes ATP-binding cassette G2 and P-glycoprotein. We also identified reversal of epithelial-to-mesenchymal transition as a new player in the Rb1 and compound K-mediated inhibition of CSCs. Rb1 and compound K treatment also inhibited the self-renewal of CSCs derived from ovarian carcinoma patients as well as in xenograft tumor model. Moreover, we did not observe toxicity in response to doses of Rb1 and compound K that produced an anti-CSC effect. Therefore, Rb1 should be explored further as a promising nutraceutical prototype of treating refractory tumors. PMID:27825116

Kingella kingae expresses four structurally distinct polysaccharide capsules that differ in their correlation with invasive disease

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

Starr, Kimberly F.; Porsch, Eric A.; Seed, Patrick C.

Kingella kingae is an encapsulated gram-negative organism that is a common cause of osteoarticular infections in young children. In earlier work, we identified a glycosyltransferase gene called csaA that is necessary for synthesis of the [3)-β-GalpNAc-(1→5)-β-Kdop-(2→] polysaccharide capsule (type a) in K. kingae strain 269–492. In the current study, we analyzed a large collection of invasive and carrier isolates from Israel and found that csaA was present in only 47% of the isolates. Further examination of this collection using primers based on the sequence that flanks csaA revealed three additional gene clusters (designated the csb, csc, and csd loci), allmore » encoding predicted glycosyltransferases. The csb locus contains the csbA, csbB, and csbC genes and is associated with a capsule that is a polymer of [6)-α-GlcpNAc-(1→5)-β-(8-OAc)Kdop-(2→] (type b). The csc locus contains the cscA, cscB, and cscC genes and is associated with a capsule that is a polymer of [3)-β-Ribf-(1→2)-β-Ribf-(1→2)-β-Ribf-(1→4)-β-Kdop-(2→] (type c). The csd locus contains the csdA, csdB, and csdC genes and is associated with a capsule that is a polymer of [P-(O→3)[β-Galp-(1→4)]-β-GlcpNAc-(1→3)-α-GlcpNAc-1-] (type d). Introduction of the csa, csb, csc, and csd loci into strain KK01Δcsa, a strain 269–492 derivative that lacks the native csaA gene, was sufficient to produce the type a capsule, type b capsule, type c capsule, and type d capsule, respectively, indicating that these loci are solely responsible for determining capsule type in K. kingae. Further analysis demonstrated that 96% of the invasive isolates express either the type a or type b capsule and that a disproportionate percentage of carrier isolates express the type c or type d capsule. Lastly, these results establish that there are at least four structurally distinct K. kingae capsule types and suggest that capsule type plays an important role in promoting K. kingae invasive disease« less

Kingella kingae expresses four structurally distinct polysaccharide capsules that differ in their correlation with invasive disease

DOE PAGES

Starr, Kimberly F.; Porsch, Eric A.; Seed, Patrick C.; ...

2016-10-19

Kingella kingae is an encapsulated gram-negative organism that is a common cause of osteoarticular infections in young children. In earlier work, we identified a glycosyltransferase gene called csaA that is necessary for synthesis of the [3)-β-GalpNAc-(1→5)-β-Kdop-(2→] polysaccharide capsule (type a) in K. kingae strain 269–492. In the current study, we analyzed a large collection of invasive and carrier isolates from Israel and found that csaA was present in only 47% of the isolates. Further examination of this collection using primers based on the sequence that flanks csaA revealed three additional gene clusters (designated the csb, csc, and csd loci), allmore » encoding predicted glycosyltransferases. The csb locus contains the csbA, csbB, and csbC genes and is associated with a capsule that is a polymer of [6)-α-GlcpNAc-(1→5)-β-(8-OAc)Kdop-(2→] (type b). The csc locus contains the cscA, cscB, and cscC genes and is associated with a capsule that is a polymer of [3)-β-Ribf-(1→2)-β-Ribf-(1→2)-β-Ribf-(1→4)-β-Kdop-(2→] (type c). The csd locus contains the csdA, csdB, and csdC genes and is associated with a capsule that is a polymer of [P-(O→3)[β-Galp-(1→4)]-β-GlcpNAc-(1→3)-α-GlcpNAc-1-] (type d). Introduction of the csa, csb, csc, and csd loci into strain KK01Δcsa, a strain 269–492 derivative that lacks the native csaA gene, was sufficient to produce the type a capsule, type b capsule, type c capsule, and type d capsule, respectively, indicating that these loci are solely responsible for determining capsule type in K. kingae. Further analysis demonstrated that 96% of the invasive isolates express either the type a or type b capsule and that a disproportionate percentage of carrier isolates express the type c or type d capsule. Lastly, these results establish that there are at least four structurally distinct K. kingae capsule types and suggest that capsule type plays an important role in promoting K. kingae invasive disease« less

The impact of a lay counselor led collaborative care intervention for common mental disorders in public and private primary care: a qualitative evaluation nested in the MANAS trial in Goa, India.

PubMed

Shinde, Sachin; Andrew, Gracy; Bangash, Omer; Cohen, Alex; Kirkwood, Betty; Patel, Vikram

2013-07-01

The MANAS trial evaluated the effectiveness of a lay counselor led collaborative stepped care intervention for Common Mental Disorders (CMD) in public and private sector primary care settings in Goa, India. This paper describes the qualitative findings of the experience of the intervention and its impact on health and psychosocial outcomes. Twenty four primary care facilities (12 public and private each) were randomized to provide either collaborative stepped care (CSC) or enhanced usual care (EUC) to adults who screen positive for CMDs. Participants were sampled purposively based on two criteria: gender and, in the CSC arm, adherence with the intervention. The qualitative study component involved two semi-structured interviews with participants of both arms (N = 115); the first interview within 2 months of recruitment and the second 6-8 months after recruitment. Data were collected between September 2007 and November 2009. More participants in the CSC than EUC arm reported relief from symptoms and an improvement in social functioning and positive impact on work and activities of daily life. The CSC participants attributed their improvement both to medication received from the doctors and the strategies suggested by the lay Health Counselors (HC). However, two key differences were observed in the results for the two types of facilities. First, the CSC participants in the public sector clinics were more likely to consider the HCs to be an important component of providing care who served as a link between patient and the doctor, provided them skills on stress management and helped in adherence to medication. Second, in the private sector, doctors performed roles similar to those of the HCs and participants in both arms placed much faith in the doctor who acted as a confidante and was perceived to understand the participant's health and context intimately. Lay counselors working in a CSC model have a positive effect on symptomatic relief, social functioning and satisfaction with care in patients with CMD attending primary care clinics although the impact, compared with usual care, is greater in the public sector. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

Telemedicine at the top of the world: the 1998 and 1999 Everest extreme expeditions.

PubMed

Angood, P B; Satava, R; Doarn, C; Merrell, R

2000-01-01

The National Aeronautics and Space Administration (NASA) initially established a Commercial Space Center (CSC) in the Department of Surgery at Yale University School of Medicine to further develop and evaluate technologies in information systems, telecommunications applied to medicine, and physiologic sensors. The CSC is known as the Medical Informatics and Technology Applications Consortium (MITAC). The overall purpose for this NASA program is to leverage technology, innovation, and resources from industry and academia through collaborative partnerships. The Yale-NASA CSC/MITAC organized the Everest Extreme Expeditions (E3) for the spring Himalayan climbing seasons in the years 1998 and 1999. The primary mission was to deliver advanced medical support with global telemedicine capabilities to one of the world's most remote and hostile settings--Mount Everest. The purpose was both humanitarian (providing medical support) and scientific (conducting medical and technology research). The Yale team provided medical care for the Everest Base Camp community; conducted validation experiments for several types of advanced medical technologies in this remote, hostile environment; and performed real-time monitoring of selected climbers, while also assessing the basic science of altitude physiology. Additionally, the teams conducted outreach medical care to the citizens of Nepal and provided several educational forums for a variety of medical and nonmedical personnel--including school-age children. As part of the project's mission, the E3 medical teams at both Nepal and New Haven were on a 24-hour emergency call system to deliver medical care in the event of a crisis. Unlike most of the teams at Everest, the mission of E3 was not to climb the 29,028-foot mountain the Nepalese call Sagarmatha ("Sky Head"). The mountain served as an extreme testing ground for telemedicine. The lessons learned from this testbed are reviewed here and further clarify the abilities to provide better health care in remote and extreme environments--which for some may even be their home environment during/after a medical illness.

Compacted Approach to Reading (CAR): An Intervention Program for At-Risk Beginning Readers.

ERIC Educational Resources Information Center

Gettys, Cynthia M.

A study determined the initial success of the Compacted Approach to Reading (CAR) program as measured at the end of the program's pilot year. Subjects were 21 first graders and 7 second graders in Tennessee identified and recommended by their first and second grade classroom teacher. The CAR program was developed based on concepts observed in the…

Human Factors Analysis and Layout Guideline Development for the Canadian Surface Combatant (CSC) Project

DTIC Science & Technology

2013-04-01

project was to provide the Royal Canadian Navy ( RCN ) with a set of guidelines on analysis, design, and verification processes for effective room...design, and verification processes that should be used in the development of effective room layouts for Royal Canadian Navy ( RCN ) ships. The primary...designed CSC; however, the guidelines could be applied to the design of any multiple-operator space in any RCN vessel. Results: The development of

TOPK (T-LAK cell-originated protein kinase) inhibitor exhibits growth suppressive effect on small cell lung cancer.

PubMed

Park, Jae-Hyun; Inoue, Hiroyuki; Kato, Taigo; Zewde, Makda; Miyamoto, Takashi; Matsuo, Yo; Salgia, Ravi; Nakamura, Yusuke

2017-03-01

T-lymphokine-activated killer cell-originated protein kinase (TOPK) plays critical roles in cancer cell proliferation as well as maintenance of cancer stem cells (CSC). Small cell lung cancer (SCLC) has highly aggressive phenotype, reveals early spread to distant sites, and results in dismal prognosis with little effective treatment. In this study, we demonstrate that TOPK expression was highly upregulated in both SCLC cell lines and primary tumors. Similar to siRNA-mediated TOPK knockdown effects, treatment with a potent TOPK inhibitor, OTS514, effectively suppressed growth of SCLC cell lines (IC 50 ; 0.4-42.6 nM) and led to their apoptotic cell death. TOPK inhibition caused cell morphologic changes in SCLC cells, elongation of intercellular bridges caused by cytokinesis defects or neuronal protrusions induced by neuronal differentiation in a subset of CSC-like SCLC cells. Treatment with OTS514 suppressed forkhead box protein M1 (FOXM1) activity, which was involved in stemness of CSC. Furthermore, OTS514 treatment reduced CD90-positive SCLC cells and showed higher cytotoxic effect against lung sphere-derived CSC-like SCLC cells. Collectively, our results suggest that targeting TOPK is a promising approach for SCLC therapy. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Cellular prion protein controls stem cell-like properties of human glioblastoma tumor-initiating cells.

PubMed

Corsaro, Alessandro; Bajetto, Adriana; Thellung, Stefano; Begani, Giulia; Villa, Valentina; Nizzari, Mario; Pattarozzi, Alessandra; Solari, Agnese; Gatti, Monica; Pagano, Aldo; Würth, Roberto; Daga, Antonio; Barbieri, Federica; Florio, Tullio

2016-06-21

Prion protein (PrPC) is a cell surface glycoprotein whose misfolding is responsible for prion diseases. Although its physiological role is not completely defined, several lines of evidence propose that PrPC is involved in self-renewal, pluripotency gene expression, proliferation and differentiation of neural stem cells. Moreover, PrPC regulates different biological functions in human tumors, including glioblastoma (GBM). We analyzed the role of PrPC in GBM cell pathogenicity focusing on tumor-initiating cells (TICs, or cancer stem cells, CSCs), the subpopulation responsible for development, progression and recurrence of most malignancies. Analyzing four GBM CSC-enriched cultures, we show that PrPC expression is directly correlated with the proliferation rate of the cells. To better define its role in CSC biology, we knocked-down PrPC expression in two of these GBM-derived CSC cultures by specific lentiviral-delivered shRNAs. We provide evidence that CSC proliferation rate, spherogenesis and in vivo tumorigenicity are significantly inhibited in PrPC down-regulated cells. Moreover, PrPC down-regulation caused loss of expression of the stemness and self-renewal markers (NANOG, Sox2) and the activation of differentiation pathways (i.e. increased GFAP expression). Our results suggest that PrPC controls the stemness properties of human GBM CSCs and that its down-regulation induces the acquisition of a more differentiated and less oncogenic phenotype.

U.S. Department of the Interior South Central Climate Science Center

USGS Publications Warehouse

Shipp, Allison A.

2012-01-01

On September 14, 2009, the Secretary of the Interior signed a Secretarial Order (No. 3289) entitled, "Addressing the Impacts of Climate Change on America's Water, Land, and Other Natural and Cultural Resources." The Order effectively established the U.S. Department of the Interior (DOI) Climate Science Centers (CSCs) for the purpose of integrating DOI science and management expertise with similar contributions from our partners to provide information to support strategic adaptation and mitigation efforts on public and private lands across the United States and internationally. The South Central Climate Science Center (SC CSC) is supported by a consortium of partners that include The University of Oklahoma, Texas Tech University, Louisiana State University, The Chickasaw Nation, The Choctaw Nation of Oklahoma, Oklahoma State University, and the National Oceanic and Atmospheric Administration's Geophysical Fluid Dynamics Laboratory. Additionally, the SC CSC will collaborate with a number of other universities, State and federal agencies, and nongovernmental organizations (NGOs) with interests and expertise in climate science. The primary partners of the SC CSC are the Landscape Conservation Cooperatives (LCCs), which include the Desert, Eastern Tallgrass Prairie and Big Rivers, Great Plains, Gulf Coast Prairie, Gulf Coastal Plains and Ozarks, and Southern Rockies. CSC collaborations are focused on common science priorities that address priority partner needs, eliminate redundancies in science, share scientific information and findings, and expand understanding of climate change impacts in the south-central United States and Mexico.

Cellular prion protein controls stem cell-like properties of human glioblastoma tumor-initiating cells

PubMed Central

Corsaro, Alessandro; Bajetto, Adriana; Thellung, Stefano; Begani, Giulia; Villa, Valentina; Nizzari, Mario; Pattarozzi, Alessandra; Solari, Agnese; Gatti, Monica; Pagano, Aldo; Würth, Roberto; Daga, Antonio; Barbieri, Federica; Florio, Tullio

2016-01-01

Prion protein (PrPC) is a cell surface glycoprotein whose misfolding is responsible for prion diseases. Although its physiological role is not completely defined, several lines of evidence propose that PrPC is involved in self-renewal, pluripotency gene expression, proliferation and differentiation of neural stem cells. Moreover, PrPC regulates different biological functions in human tumors, including glioblastoma (GBM). We analyzed the role of PrPC in GBM cell pathogenicity focusing on tumor-initiating cells (TICs, or cancer stem cells, CSCs), the subpopulation responsible for development, progression and recurrence of most malignancies. Analyzing four GBM CSC-enriched cultures, we show that PrPC expression is directly correlated with the proliferation rate of the cells. To better define its role in CSC biology, we knocked-down PrPC expression in two of these GBM-derived CSC cultures by specific lentiviral-delivered shRNAs. We provide evidence that CSC proliferation rate, spherogenesis and in vivo tumorigenicity are significantly inhibited in PrPC down-regulated cells. Moreover, PrPC down-regulation caused loss of expression of the stemness and self-renewal markers (NANOG, Sox2) and the activation of differentiation pathways (i.e. increased GFAP expression). Our results suggest that PrPC controls the stemness properties of human GBM CSCs and that its down-regulation induces the acquisition of a more differentiated and less oncogenic phenotype. PMID:27229535

Medullospheres from DAOY, UW228 and ONS-76 cells: increased stem cell population and proteomic modifications.

PubMed

Zanini, Cristina; Ercole, Elisabetta; Mandili, Giorgia; Salaroli, Roberta; Poli, Alice; Renna, Cristiano; Papa, Valentina; Cenacchi, Giovanna; Forni, Marco

2013-01-01

Medulloblastoma (MB) is an aggressive pediatric tumor of the Central Nervous System (CNS) usually treated according to a refined risk stratification. The study of cancer stem cells (CSC) in MB is a promising approach aimed at finding new treatment strategies. The CSC compartment was studied in three characterized MB cell lines (DAOY, UW228 and ONS-76) grown in standard adhesion as well as being grown as spheres, which enables expansion of the CSC population. MB cell lines, grown in adherence and as spheres, were subjected to morphologic analysis at the light and electron microscopic level, as well as cytofluorimetric determinations. Medullospheres (MBS) were shown to express increasingly immature features, along with the stem cells markers: CD133, Nestin and β-catenin. Proteomic analysis highlighted the differences between MB cell lines, demonstrating a unique protein profile for each cell line, and minor differences when grown as spheres. In MBS, MALDI-TOF also identified some proteins, that have been linked to tumor progression and resistance, such as Nucleophosmin (NPM). In addition, immunocytochemistry detected Sox-2 as a stemness marker of MBS, as well as confirming high NPM expression. Culture conditioning based on low attachment flasks and specialized medium may provide new data on the staminal compartment of CNS tumors, although a proteomic profile of CSC is still elusive for MB.

Medullospheres from DAOY, UW228 and ONS-76 Cells: Increased Stem Cell Population and Proteomic Modifications

PubMed Central

Zanini, Cristina; Ercole, Elisabetta; Mandili, Giorgia; Salaroli, Roberta; Poli, Alice; Renna, Cristiano; Papa, Valentina; Cenacchi, Giovanna; Forni, Marco

2013-01-01

Background Medulloblastoma (MB) is an aggressive pediatric tumor of the Central Nervous System (CNS) usually treated according to a refined risk stratification. The study of cancer stem cells (CSC) in MB is a promising approach aimed at finding new treatment strategies. Methodology/Principal Findings The CSC compartment was studied in three characterized MB cell lines (DAOY, UW228 and ONS-76) grown in standard adhesion as well as being grown as spheres, which enables expansion of the CSC population. MB cell lines, grown in adherence and as spheres, were subjected to morphologic analysis at the light and electron microscopic level, as well as cytofluorimetric determinations. Medullospheres (MBS) were shown to express increasingly immature features, along with the stem cells markers: CD133, Nestin and β-catenin. Proteomic analysis highlighted the differences between MB cell lines, demonstrating a unique protein profile for each cell line, and minor differences when grown as spheres. In MBS, MALDI-TOF also identified some proteins, that have been linked to tumor progression and resistance, such as Nucleophosmin (NPM). In addition, immunocytochemistry detected Sox-2 as a stemness marker of MBS, as well as confirming high NPM expression. Conclusions/Significance Culture conditioning based on low attachment flasks and specialized medium may provide new data on the staminal compartment of CNS tumors, although a proteomic profile of CSC is still elusive for MB. PMID:23717474

[Key effect genes responding to nerve injury identified by gene ontology and computer pattern recognition].

PubMed

Pan, Qian; Peng, Jin; Zhou, Xue; Yang, Hao; Zhang, Wei

2012-07-01

In order to screen out important genes from large gene data of gene microarray after nerve injury, we combine gene ontology (GO) method and computer pattern recognition technology to find key genes responding to nerve injury, and then verify one of these screened-out genes. Data mining and gene ontology analysis of gene chip data GSE26350 was carried out through MATLAB software. Cd44 was selected from screened-out key gene molecular spectrum by comparing genes' different GO terms and positions on score map of principal component. Function interferences were employed to influence the normal binding of Cd44 and one of its ligands, chondroitin sulfate C (CSC), to observe neurite extension. Gene ontology analysis showed that the first genes on score map (marked by red *) mainly distributed in molecular transducer activity, receptor activity, protein binding et al molecular function GO terms. Cd44 is one of six effector protein genes, and attracted us with its function diversity. After adding different reagents into the medium to interfere the normal binding of CSC and Cd44, varying-degree remissions of CSC's inhibition on neurite extension were observed. CSC can inhibit neurite extension through binding Cd44 on the neuron membrane. This verifies that important genes in given physiological processes can be identified by gene ontology analysis of gene chip data.

FOXC2 regulates the G2/M transition of stem cell-rich breast cancer cells and sensitizes them to PLK1 inhibition

PubMed Central

Pietilä, Mika; Vijay, Geraldine V.; Soundararajan, Rama; Yu, Xian; Symmans, William F.; Sphyris, Nathalie; Mani, Sendurai A.

2016-01-01

Cancer cells with stem cell properties (CSCs) underpin the chemotherapy resistance and high therapeutic failure of triple-negative breast cancers (TNBCs). Even though CSCs are known to proliferate more slowly, they are sensitive to inhibitors of G2/M kinases such as polo-like kinase 1 (PLK1). Understanding the cell cycle regulatory mechanisms of CSCs will help target these cells more efficiently. Herein, we identify a novel role for the transcription factor FOXC2, which is mostly expressed in CSCs, in the regulation of cell cycle of CSC-enriched breast cancer cells. We demonstrate that FOXC2 expression is regulated in a cell cycle-dependent manner, with FOXC2 protein levels accumulating in G2, and rapidly decreasing during mitosis. Knockdown of FOXC2 in CSC-enriched TNBC cells delays mitotic entry without significantly affecting the overall proliferation rate of these cells. Moreover, PLK1 activity is important for FOXC2 protein stability, since PLK1 inhibition reduces FOXC2 protein levels. Indeed, FOXC2 expressing CSC-enriched TNBC cells are sensitive to PLK1 inhibition. Collectively, our findings demonstrate a novel role for FOXC2 as a regulator of the G2/M transition and elucidate the reason for the observed sensitivity of CSC-enriched breast cancer cells to PLK1 inhibitor. PMID:27064522

Breast Cancer Stem Cell Therapeutics, Multiple Strategies Versus Using Engineered Mesenchymal Stem Cells With Notch Inhibitory Properties: Possibilities and Perspectives.

PubMed

Bose, Bipasha; Sen, Utsav; Shenoy P, Sudheer

2018-01-01

Relapse cases of cancers are more vigorous and difficult to control due to the preponderance of cancer stem cells (CSCs). Such CSCs that had been otherwise dormant during the first incidence of cancer gradually appear as radiochemoresistant cancer cells. Hence, cancer therapeutics aimed at CSCs would be an effective strategy for mitigating the cancers during relapse. Alternatively, CSC therapy can also be proposed as an adjuvant therapy, along-with the conventional therapies. As regenerative stem cells (RSCs) are known for their trophic effects, anti-tumorogenicity, and better migration toward an injury site, this review aims to address the use of adult stem cells such as dental pulp derived; cord blood derived pure populations of regenerative stem cells for targeting CSCs. Indeed, pro-tumorogenicity of RSCs is of concern and hence has also been dealt with in relation to breast CSC therapeutics. Furthermore, as notch signaling pathways are upregulated in breast cancers, and anti-notch antibody based and sh-RNA based therapies are already in the market, this review focuses the possibilities of engineering RSCs to express notch inhibitory proteins for breast CSC therapeutics. Also, we have drawn a comparison among various possibilities of breast CSC therapeutics, about, notch1 inhibition. J. Cell. Biochem. 119: 141-149, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Targeting tissue factor as a novel therapeutic oncotarget for eradication of cancer stem cells isolated from tumor cell lines, tumor xenografts and patients of breast, lung and ovarian cancer.

PubMed

Hu, Zhiwei; Xu, Jie; Cheng, Jijun; McMichael, Elizabeth; Yu, Lianbo; Carson, William E

2017-01-03

Targeting cancer stem cell (CSC) represents a promising therapeutic approach as it can potentially fight cancer at its root. The challenge is to identify a surface therapeutic oncotarget on CSC. Tissue factor (TF) is known as a common yet specific surface target for cancer cells and tumor neovasculature in several solid cancers. However, it is unknown if TF is expressed by CSCs. Here we demonstrate that TF is constitutively expressed on CD133 positive (CD133+) or CD24-CD44+ CSCs isolated from human cancer cell lines, tumor xenografts from mice and breast tumor tissues from patients. TF-targeted agents, i.e., a factor VII (fVII)-conjugated photosensitizer (fVII-PS for targeted photodynamic therapy) and fVII-IgG1Fc (Immunoconjugate or ICON for immunotherapy), can eradicate CSC via the induction of apoptosis and necrosis and via antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity, respectively. In conclusion, these results demonstrate that TF is a novel surface therapeutic oncotarget for CSC, in addition to cancer cell TF and tumor angiogenic vascular endothelial TF. Moreover, this research highlights that TF-targeting therapeutics can effectively eradicate CSCs, without drug resistance, isolated from breast, lung and ovarian cancer with potential to translate into other most commonly diagnosed solid cancer, in which TF is also highly expressed.

Results from a pilot study of a computer-based role-playing game for young people with psychosis.

PubMed

Olivet, Jeffrey; Haselden, Morgan; Piscitelli, Sarah; Kenney, Rachael; Shulman, Alexander; Medoff, Deborah; Dixon, Lisa

2018-03-15

Recent research on first episode psychosis (FEP) has demonstrated the effectiveness of coordinated specialty care (CSC) models to support young adults and their families, yet few tools exist to promote engagement in care. This study aimed to develop a prototype computer-based role-playing game (RPG) designed for young people who have experienced FEP, and conduct a pilot study to determine feasibility and test whether the game improves consumers' attitudes toward treatment and recovery. Twenty young people with FEP who were receiving services at a CSC program enrolled in the study and played the game for 1 hour. Pre- and post-quantitative assessments measured change in hope, recovery, stigma, empowerment and engagement in treatment. Qualitative interviews explored participants' experience with the game and ideas for further product development. Participants showed significant increase in positive attitudes toward recovery. The qualitative findings further demonstrated the game's positive impact across these domains. Of all game features, participants most highly valued video testimonials of other young adults with FEP telling their stories of hope and recovery. These findings provide modest support for the potential benefits of this type of computer-based RPG, if further developed for individuals experiencing psychosis. © 2018 John Wiley & Sons Australia, Ltd.

Targeting CXCR1/2 Significantly Reduces Breast Cancer Stem Cell Activity and Increases the Efficacy of Inhibiting HER2 via HER2-dependent and -independent Mechanisms

PubMed Central

Singh, Jagdeep K.; Farnie, Gillian; Bundred, Nigel J.; Simões, Bruno M; Shergill, Amrita; Landberg, Göran; Howell, Sacha; Clarke, Robert B.

2012-01-01

Purpose Breast cancer stem-like cells (CSCs) are an important therapeutic target as they are predicted to be responsible for tumour initiation, maintenance and metastases. Interleukin-8 (IL-8) is upregulated in breast cancer and associated with poor prognosis. Breast cancer cell line studies indicate that IL-8 via its cognate receptors, CXCR1 and CXCR2, is important in regulating breast CSC activity. We investigated the role of IL-8 in the regulation of CSC activity using patient-derived breast cancers and determined the potential benefit of combining CXCR1/2 inhibition with HER2-targeted therapy. Experimental design CSC activity of metastatic and invasive human breast cancers (n=19) was assessed ex vivo using the mammosphere colony forming assay. Results Metastatic fluid IL-8 level correlated directly with mammosphere formation (r=0.652; P<0.05; n=10). Recombinant IL-8 directly increased mammosphere formation/self-renewal in metastatic and invasive breast cancers (n=17). IL-8 induced activation of EGFR/HER2 and downstream signalling pathways and effects were abrogated by inhibition of SRC, EGFR/HER2, PI3K or MEK. Furthermore, lapatinib inhibited the mammosphere-promoting effect of IL-8 in both HER2-positive and negative patient-derived cancers. CXCR1/2 inhibition also blocked the effect of IL-8 on mammosphere formation and added to the efficacy of lapatinib in HER2-positive cancers. Conclusions These studies establish a role for IL-8 in the regulation of patient-derived breast CSC activity and demonstrate that IL-8/CXCR1/2 signalling is partly mediated via a novel SRC and EGFR/HER2-dependent pathway. Combining CXCR1/2 inhibitors with current HER2-targeted therapies has potential as an effective therapeutic strategy to reduce CSC activity in breast cancer and improve the survival of HER2-positive patients. PMID:23149820

The Chandra Source Catalog

NASA Astrophysics Data System (ADS)

Evans, Ian N.; Primini, F. A.; Glotfelty, K. J.; Anderson, C. S.; Bonaventura, N. R.; Chen, J. C.; Davis, J. E.; Doe, S. M.; Evans, J. D.; Fabbiano, G.; Galle, E. C.; Gibbs, D. G., II; Grier, J. D.; Hain, R. M.; Hall, D. M.; Harbo, P. N.; He, X.; Houck, J. C.; Karovska, M.; Kashyap, V. L.; Lauer, J.; McCollough, M. L.; McDowell, J. C.; Miller, J. B.; Mitschang, A. W.; Morgan, D. L.; Mossman, A. E.; Nichols, J. S.; Nowak, M. A.; Plummer, D. A.; Refsdal, B. L.; Rots, A. H.; Siemiginowska, A.; Sundheim, B. A.; Tibbetts, M. S.; Van Stone, D. W.; Winkelman, S. L.; Zografou, P.

2010-03-01

The Chandra Source Catalog (CSC) is a general purpose virtual X-ray astrophysics facility that provides access to a carefully selected set of generally useful quantities for individual X-ray sources, and is designed to satisfy the needs of a broad-based group of scientists, including those who may be less familiar with astronomical data analysis in the X-ray regime. The first release of the CSC includes information about 94,676 distinct X-ray sources detected in a subset of public ACIS imaging observations from roughly the first eight years of the Chandra mission. This release of the catalog includes point and compact sources with observed spatial extents < 30". The catalog (1) provides access to estimates of the X-ray source properties for detected sources with good scientific fidelity; (2) facilitates analysis of a wide range of statistical properties for classes of X-ray sources; and (3) provides efficient access to calibrated observational data and ancillary data products for individual X-ray sources. The catalog includes real X-ray sources detected with flux estimates that are at least 3 times their estimated 1σ uncertainties in at least one energy band, while maintaining the number of spurious sources at a level of < 1 false source per field for a 100 ks observation. For each detected source, the CSC provides commonly tabulated quantities, including source position, extent, multi-band fluxes, hardness ratios, and variability statistics. In addition, for each X-ray source the CSC includes an extensive set of file-based data products that can be manipulated interactively, including source images, event lists, light curves, and spectra. Support for development of the CSC is provided by the National Aeronautics and Space Administration through the Chandra X-ray Center, which is operated by the Smithsonian Astrophysical Observatory for and on behalf of the National Aeronautics and Space Administration under contract NAS 8-03060.

SU-F-T-683: Cancer Stem Cell Hypothesis and Radiation Treatments

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

Fourkal, E

Purpose: The tumor control probability in radiation therapy allows comparing different radiation treatments to each other by means of calculating the probability that a prescribed dose of radiation eradicates or controls the tumor. In the conventional approach, all cancer cells can divide unlimited number of times and the tumor control often means eradicating every malignant cell by the radiation. In recent years however, there is a mounting consensus that in a given tumor volume there is a sub-population of cells, known as cancer stem cells (CSCs) that are responsible for tumor initiation and growth. Other or progenitor cancer cells canmore » only divide limited number of times. This entails that only cancer stem cells may nned to be eliminated in order to control the tumor. Thus one may define TCP as the probability of eliminating CSCs for the given dose of radiation. Methods: Using stochastic methods, specifically the birth-and-death Markov processes, an infinite system of equations is set for probabilities of having m cancer stem cells at time t after the start of radiation. The TCP is calculated as the probability of no cancer stem cells surviving the radiation. Two scenarios are studied. In the first situation, the TCP is calculated for a unidirectional case when CSC gives birth to another CSC or a progenitor cell. In the second scenario, a bidirectional model is studied where the progenitor cell gives rise to CSC. Results: The proposed calculations show that the calculated TCP for CSC depends on whether one adopts unidirectional or bidirectional conversion models. The bidirectional model shows significantly lower TCP values for the given dose delivered to the tumor. Conclusion: Incorporating CSC hypothesis into the TCP modeling may notably influence the dose prescription as well as the concept of the expected TCP after the radiation treatments.« less

E-Cigarette Affects the Metabolome of Primary Normal Human Bronchial Epithelial Cells

PubMed Central

Aug, Argo; Altraja, Siiri; Kilk, Kalle; Porosk, Rando; Soomets, Ursel; Altraja, Alan

2015-01-01

E-cigarettes are widely believed to be safer than conventional cigarettes and have been even suggested as aids for smoking cessation. However, while reasonable with some regards, this judgment is not yet supported by adequate biomedical research data. Since bronchial epithelial cells are the immediate target of inhaled toxicants, we hypothesized that exposure to e-cigarettes may affect the metabolome of human bronchial epithelial cells (HBEC) and that the changes are, at least in part, induced by oxidant-driven mechanisms. Therefore, we evaluated the effect of e-cigarette liquid (ECL) on the metabolome of HBEC and examined the potency of antioxidants to protect the cells. We assessed the changes of the intracellular metabolome upon treatment with ECL in comparison of the effect of cigarette smoke condensate (CSC) with mass spectrometry and principal component analysis on air-liquid interface model of normal HBEC. Thereafter, we evaluated the capability of the novel antioxidant tetrapeptide O-methyl-l-tyrosinyl-γ-l-glutamyl-l-cysteinylglycine (UPF1) to attenuate the effect of ECL. ECL caused a significant shift in the metabolome that gradually gained its maximum by the 5th hour and receded by the 7th hour. A second alteration followed at the 13th hour. Treatment with CSC caused a significant initial shift already by the 1st hour. ECL, but not CSC, significantly increased the concentrations of arginine, histidine, and xanthine. ECL, in parallel with CSC, increased the content of adenosine diphosphate and decreased that of three lipid species from the phosphatidylcholine family. UPF1 partially counteracted the ECL-induced deviations, UPF1’s maximum effect occurred at the 5th hour. The data support our hypothesis that ECL profoundly alters the metabolome of HBEC in a manner, which is comparable and partially overlapping with the effect of CSC. Hence, our results do not support the concept of harmlessness of e-cigarettes. PMID:26536230

E-Cigarette Affects the Metabolome of Primary Normal Human Bronchial Epithelial Cells.

PubMed

Aug, Argo; Altraja, Siiri; Kilk, Kalle; Porosk, Rando; Soomets, Ursel; Altraja, Alan

2015-01-01

E-cigarettes are widely believed to be safer than conventional cigarettes and have been even suggested as aids for smoking cessation. However, while reasonable with some regards, this judgment is not yet supported by adequate biomedical research data. Since bronchial epithelial cells are the immediate target of inhaled toxicants, we hypothesized that exposure to e-cigarettes may affect the metabolome of human bronchial epithelial cells (HBEC) and that the changes are, at least in part, induced by oxidant-driven mechanisms. Therefore, we evaluated the effect of e-cigarette liquid (ECL) on the metabolome of HBEC and examined the potency of antioxidants to protect the cells. We assessed the changes of the intracellular metabolome upon treatment with ECL in comparison of the effect of cigarette smoke condensate (CSC) with mass spectrometry and principal component analysis on air-liquid interface model of normal HBEC. Thereafter, we evaluated the capability of the novel antioxidant tetrapeptide O-methyl-l-tyrosinyl-γ-l-glutamyl-l-cysteinylglycine (UPF1) to attenuate the effect of ECL. ECL caused a significant shift in the metabolome that gradually gained its maximum by the 5th hour and receded by the 7th hour. A second alteration followed at the 13th hour. Treatment with CSC caused a significant initial shift already by the 1st hour. ECL, but not CSC, significantly increased the concentrations of arginine, histidine, and xanthine. ECL, in parallel with CSC, increased the content of adenosine diphosphate and decreased that of three lipid species from the phosphatidylcholine family. UPF1 partially counteracted the ECL-induced deviations, UPF1's maximum effect occurred at the 5th hour. The data support our hypothesis that ECL profoundly alters the metabolome of HBEC in a manner, which is comparable and partially overlapping with the effect of CSC. Hence, our results do not support the concept of harmlessness of e-cigarettes.

Inhibition of Notch signaling alters the phenotype of orthotopic tumors formed from glioblastoma multiforme neurosphere cells but does not hamper intracranial tumor growth regardless of endogene Notch pathway signature.

PubMed

Kristoffersen, Karina; Nedergaard, Mette Kjølhede; Villingshøj, Mette; Borup, Rehannah; Broholm, Helle; Kjær, Andreas; Poulsen, Hans Skovgaard; Stockhausen, Marie-Thérése

2014-07-01

Brain cancer stem-like cells (bCSC) are cancer cells with neural stem cell (NSC)-like properties found in the devastating brain tumor glioblastoma multiforme (GBM). bCSC are proposed a central role in tumor initiation, progression, treatment resistance and relapse and as such present a promising target in GBM research. The Notch signaling pathway is often deregulated in GBM and we have previously characterized GBM-derived bCSC cultures based on their expression of the Notch-1 receptor and found that it could be used as predictive marker for the effect of Notch inhibition. The aim of the present project was therefore to further elucidate the significance of Notch pathway activity for the tumorigenic properties of GBM-derived bCSC. Human-derived GBM xenograft cells previously established as NSC-like neurosphere cultures were used. Notch inhibition was accomplished by exposing the cells to the gamma-secretase inhibitor DAPT prior to gene expression analysis and intracranial injection into immunocompromised mice. By analyzing the expression of several Notch pathway components, we found that the cultures indeed displayed different Notch pathway signatures. However, when DAPT-treated neurosphere cells were injected into the brain of immunocompromised mice, no increase in survival was obtained regardless of Notch pathway signature and Notch inhibition. We did however observe a decrease in the expression of the stem cell marker Nestin, an increase in the proliferative marker Ki-67 and an increased number of abnormal vessels in tumors formed from DAPT-treated, high Notch-1 expressing cultures, when compared with the control. Based on the presented results we propose that Notch inhibition partly induces differentiation of bCSC, and selects for a cell type that more strongly induces angiogenesis if the treatment is not sustained. However, this more differentiated cell type might prove to be more sensitive to conventional therapies.

Curcumin effectively inhibits oncogenic NF-kB signaling and restrains stemness features in liver cancer

PubMed Central

Marquardt, Jens U.; Gomez-Quiroz, Luis; Camacho, Lucrecia O. Arreguin; Pinna, Federico; Lee, Yun-Han; Kitade, Mitsuteru; Domínguez, Mayrel Palestino; Castven, Darko; Breuhahn, Kai; Conner, Elizabeth A.; Galle, Peter R.; Andersen, Jesper B.; Factor, Valentina M.; Thorgeirsson, Snorri S.

2015-01-01

Background & Aims The cancer stem cells (CSCs) have important therapeutic implications for multi-resistant cancers including hepatocellular carcinoma (HCC). Among the key pathways frequently activated in liver CSCs is NF-kB signaling. Methods We evaluated the CSCs-depleting potential of NF-kB inhibition in liver cancer achieved by the IKK inhibitor curcumin, RNAi and specific peptide SN50. The effects on CSCs were assessed by analysis of Side Population (SP), sphere formation and tumorigenicity. Molecular changes were determined by RT-qPCR, global gene expression microarray, EMSA, and Western blotting. Results HCC cell lines exposed to curcumin exhibited differential responses to curcumin and were classified as sensitive and resistant. In sensitive lines, curcumin-mediated induction of cell death was directly related to the extent of NF-kB inhibition. The treatment also led to a selective CSC-depletion as evidenced by a reduced SP size, decreased sphere formation, down-regulation of CSC markers and suppressed tumorigenicity. Similarly, NF-kB inhibition by SN50 and siRNA against p65 suppressed tumor cell growth. In contrast, curcumin-resistant cells displayed a paradoxical increase in proliferation and expression of CSC markers. Mechanistically, an important component of the CSC-depleting activity of curcumin could be attributed to a NF-kB-mediated HDAC inhibition. Co-administration of the class I/II HDAC inhibitor trichostatine sensitized resistant cells to curcumin. Further, integration of a predictive signature of curcumin sensitivity with human HCC database indicated that HCCs with poor prognosis and progenitor features are most likely to benefit from NF-kB inhibition. Conclusions These results demonstrate that blocking NF-kB can specifically target CSC populations and suggest a potential for combined inhibition of NF-kB and HDAC signaling for treatment of liver cancer patients with poor prognosis. PMID:25937435

Age-related increase in Wnt inhibitor causes a senescence-like phenotype in human cardiac stem cells

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

Nakamura, Tamami; Hosoyama, Tohru; Regenerative Medicine Institute, Yamaguchi University Graduate School of Medicine

Aging of cardiac stem/progenitor cells (CSCs) impairs heart regeneration and leads to unsatisfactory outcomes of cell-based therapies. As the precise mechanisms underlying CSC aging remain unclear, the use of therapeutic strategies for elderly patients with heart failure is severely delayed. In this study, we used human cardiosphere-derived cells (CDCs), a subtype of CSC found in the postnatal heart, to identify secreted factor(s) associated with CSC aging. Human CDCs were isolated from heart failure patients of various ages (2–83 years old). Gene expression of key soluble factors was compared between CDCs derived from young and elderly patients. Among these factors, SFRP1,more » a gene encoding a Wnt antagonist, was significantly up-regulated in CDCs from elderly patients (≥65 years old). sFRP1 levels was increased significantly also in CDCs, whose senescent phenotype was induced by anti-cancer drug treatment. These results suggest the participation of sFRP1 in CSC aging. We show that the administration of recombinant sFRP1 induced cellular senescence in CDCs derived from young patients, as indicated by increased levels of markers such as p16, and a senescence-associated secretory phenotype. In addition, co-administration of recombinant sFRP1 could abrogate the accelerated CDC proliferation induced by Wnt3A. Taken together, our results suggest that canonical Wnt signaling and its antagonist, sFRP1, regulate proliferation of human CSCs. Furthermore, excess sFRP1 in elderly patients causes CSC aging. - Highlights: • Wnt signaling regulates proliferation of human cardiac stem cells. • Expression of sFRP1, which is a Wnt antagonist, is up-regulated in elderly patients with heart failure. • Expression of sFRP1 is increased in anti-cancer drug-induced senescent human cardiac stem cells. • sFRP1 causes cellular senescence of young patients-derived cardiac stem cells.« less

[Selective retina therapy in central serous chorioretinopathy with detachment of the pigmentary epithelium].

PubMed

Klatt, C; Elsner, H; Pörksen, E; Brinkmann, R; Bunse, A; Birngruber, R; Roider, J

2006-10-01

Selective Retina Therapy (SRT) is a new and innovative laser treatment modality that selectively treats the retinal pigmentary epithelium while sparing the photoreceptors. This therapeutic concept appears to be particularly suitable for treating patients with acute or chronic central serous chorioretinopathy (CSC). We present preliminary results obtained in five patients who had CSC associated with pigmentary epithelium detachment (PED) and serous subretinal fluid (SRF) and who were treated with SRT. This case series was made up of five male patients (mean age 47 years) with chronic CSC and SRF resulting from PED. Examinations performed before and at 1 month and 3 months after the treatment were: BCVA, FLA, OCT (Zeiss OCT III). For SRT, confluent treatment of the PED (area of leakage) was carried out using a pulsed frequency-doubled, Q-switched Nd-YLF prototype laser (lambda=527 nm, t= 1.7 s, 100 Hz, energy = 150-250 J). Best corrected visual acuity at baseline was 0.53, while after 4 weeks it was 0.56 and after 12 weeks, 0.5. At baseline leakage was seen at the PED on fluorescein angiography in all patients. After 4 weeks leakage activity was no longer noted on angiography in 4 of 5 patients. OCT at baseline showed SRF at the edge of the PED in all patients, but in 4 of the 5 patients this was no longer detectable after 4 weeks. SRT is a safe and effective treatment for patients with CSC in which PED has caused SRF. Not a single case of rip syndrome was observed in this study, even though the PED was treated confluently. Since SRT spares the photoreceptors it is particularly suitable for the treatment of CSC, especially when the origin of leakage is located close to the fovea. The results indicate that SRT leads to reconstruction of the outer blood-retina barrier.

Genetic profiling of putative breast cancer stem cells from malignant pleural effusions.

PubMed

Tiran, Verena; Stanzer, Stefanie; Heitzer, Ellen; Meilinger, Michael; Rossmann, Christopher; Lax, Sigurd; Tsybrovskyy, Oleksiy; Dandachi, Nadia; Balic, Marija

2017-01-01

A common symptom during late stage breast cancer disease is pleural effusion, which is related to poor prognosis. Malignant cells can be detected in pleural effusions indicating metastatic spread from the primary tumor site. Pleural effusions have been shown to be a useful source for studying metastasis and for isolating cells with putative cancer stem cell (CSC) properties. For the present study, pleural effusion aspirates from 17 metastatic breast cancer patients were processed to propagate CSCs in vitro. Patient-derived aspirates were cultured under sphere forming conditions and isolated primary cultures were further sorted for cancer stem cell subpopulations ALDH1+ and CD44+CD24-/low. Additionally, sphere forming efficiency of CSC and non-CSC subpopulations was determined. In order to genetically characterize the different tumor subpopulations, DNA was isolated from pleural effusions before and after cell sorting, and compared with corresponding DNA copy number profiles from primary tumors or bone metastasis using low-coverage whole genome sequencing (SCNA-seq). In general, unsorted cells had a higher potential to form spheres when compared to CSC subpopulations. In most cases, cell sorting did not yield sufficient cells for copy number analysis. A total of five from nine analyzed unsorted pleura samples (55%) showed aberrant copy number profiles similar to the respective primary tumor. However, most sorted subpopulations showed a balanced profile indicating an insufficient amount of tumor cells and low sensitivity of the sequencing method. Finally, we were able to establish a long term cell culture from one pleural effusion sample, which was characterized in detail. In conclusion, we confirm that pleural effusions are a suitable source for enrichment of putative CSC. However, sequencing based molecular characterization is impeded due to insufficient sensitivity along with a high number of normal contaminating cells, which are masking genetic alterations of rare cancer (stem) cells.

Curcumin effectively inhibits oncogenic NF-κB signaling and restrains stemness features in liver cancer.

PubMed

Marquardt, Jens U; Gomez-Quiroz, Luis; Arreguin Camacho, Lucrecia O; Pinna, Federico; Lee, Yun-Han; Kitade, Mitsuteru; Domínguez, Mayrel Palestino; Castven, Darko; Breuhahn, Kai; Conner, Elizabeth A; Galle, Peter R; Andersen, Jesper B; Factor, Valentina M; Thorgeirsson, Snorri S

2015-09-01

The cancer stem cells (CSCs) have important therapeutic implications for multi-resistant cancers including hepatocellular carcinoma (HCC). Among the key pathways frequently activated in liver CSCs is NF-κB signaling. We evaluated the CSCs-depleting potential of NF-κB inhibition in liver cancer achieved by the IKK inhibitor curcumin, RNAi and specific peptide SN50. The effects on CSCs were assessed by analysis of side population (SP), sphere formation and tumorigenicity. Molecular changes were determined by RT-qPCR, global gene expression microarray, EMSA, and Western blotting. HCC cell lines exposed to curcumin exhibited differential responses to curcumin and were classified as sensitive and resistant. In sensitive lines, curcumin-mediated induction of cell death was directly related to the extent of NF-κB inhibition. The treatment also led to a selective CSC-depletion as evidenced by a reduced SP size, decreased sphere formation, down-regulation of CSC markers and suppressed tumorigenicity. Similarly, NF-κB inhibition by SN50 and siRNA against p65 suppressed tumor cell growth. In contrast, curcumin-resistant cells displayed a paradoxical increase in proliferation and expression of CSC markers. Mechanistically, an important component of the CSC-depleting activity of curcumin could be attributed to a NF-κB-mediated HDAC inhibition. Co-administration of the class I/II HDAC inhibitor trichostatine sensitized resistant cells to curcumin. Further, integration of a predictive signature of curcumin sensitivity with human HCC database indicated that HCCs with poor prognosis and progenitor features are most likely to benefit from NF-κB inhibition. These results demonstrate that blocking NF-κB can specifically target CSC populations and suggest a potential for combined inhibition of NF-κB and HDAC signaling for treatment of liver cancer patients with poor prognosis. Copyright © 2015 European Association for the Study of the Liver. All rights reserved.

Educators' Perceptions and Value of Career and Technical Education Programs

ERIC Educational Resources Information Center

Shanklin, Stacey L.

2014-01-01

It is not known the extent to which CTE teachers compared to core teachers, student advisors, and administrators perceive the value of CTE programs in relationship to the 21st century skills needed for success in employment and postsecondary endeavors and the professional relationships needed to adequately support and grow CTE programs. The sample…

Operations analysis (study 2.1). Program listing for the LOVES computer code

NASA Technical Reports Server (NTRS)

Wray, S. T., Jr.

1974-01-01

A listing of the LOVES computer program is presented. The program is coded partially in SIMSCRIPT and FORTRAN. This version of LOVES is compatible with both the CDC 7600 and the UNIVAC 1108 computers. The code has been compiled, loaded, and executed successfully on the EXEC 8 system for the UNIVAC 1108.

Increasing Diversity in Science and Health Professions: A 21-Year Longitudinal Study Documenting College and Career Success

ERIC Educational Resources Information Center

Winkleby, Marilyn A.; Ned, Judith; Ahn, David; Koehler, Alana; Kennedy, Jeanne D.

2009-01-01

Despite decades of precollege science education programs, African Americans, Latinos, and Native Americans remain critically underrepresented in science and health professions. This report describes college and career outcomes among graduates of the Stanford Medical Youth Science Program (SMYSP), a 5-week summer residential program for low-income…

A 3D Cellular Automaton for Cell Differentiation in a Solid Tumor with Plasticity

NASA Astrophysics Data System (ADS)

Margarit, David H.; Romanelli, Lilia; Fendrik, Alejandro J.

A model with spherical symmetry is proposed. We analyze the appropriate parameters of cell differentiation for different kinds of cells (Cancer Stem Cells (CSC) and Differentiated Cells (DC)). The plasticity (capacity to return from a DC to its previous state of CSC) is taken into account. Following this hypothesis, the dissemination of CSCs to another organ is analyzed. The location of the cells in the tumor and the plasticity range for possible metastasis is discussed.

Differentiation of Neonatal Human-Induced Pluripotent Stem Cells to Prostate Epithelial Cells: A Model to Study Prostate Cancer Development

DTIC Science & Technology

2013-06-01

38, 40, 41]. Because these “ mela - noma stem cells” (MSC) are sometimes so numerous, some have argued that the CSC model may not apply to melanoma...40]. There are data from two groups indicating that mela - noma lesions contain a CSC subset character- ized by CD271 expression [25, 26]. In a...neuronal proteins and neuron- like differentiation has been long recognized in neoplastic melanocytes [46, 47]. Certain mela - noma cell lines that

ADST Software Design Document for the BDS-D VIDS-equipped M1

DTIC Science & Technology

1993-09-10

system responds to perceived threats in the following ways:I a. by displaying visual icons on the Commander’s Controls Display Panel (CCDP). b. by...also referred to as the Soldier Machine Interface (SMI) and the Commander’s Controls Display Panel (CCDP). 3.2.1. VIDS-GT CSC The VIDS-GT CSC handles...countermeasure will be activated first in Individual_CM_Simul. 4.1.3.4.3. IndividualCMSimul CSU IndividualCM-Simul controls the activation and deactivation of

Sensitivity of Breast Cancer Stem Cells to TRA-8 Anti-DR5 Monoclonal Antibody

DTIC Science & Technology

2012-02-01

cytotoxicity and reduction in BrCSC marker expression. A. 2LMP cells were sorted using flow cytometry for CD44+/CD24-/ALDHhigh. Cells were pre...cells were sorted using flow cytometry for ALDH? cells and allowed to form primary tumorspheres for 3 days. After tumorspheres were mechanically...n =5 ) Day Fig. 5 Effect of ex vivo treatment of BrCSC enriched cells on tumorgenicity in NOD/SCID mice. 2LMP cells were sorted using flow cytometry

34 CFR 415.21 - What selection criteria does the Secretary use?

Code of Federal Regulations, 2010 CFR

2010-07-01

... occupational needs; (3) Provide trainees with appropriate vocational evaluation, assessment, and counseling... program, as evidenced by empirical data from those programs, in such factors as— (i) Student performance... students in jobs, including military service; and (iv) Successful transfer of students to a variety of...

34 CFR 415.21 - What selection criteria does the Secretary use?

Code of Federal Regulations, 2011 CFR

2011-07-01

... occupational needs; (3) Provide trainees with appropriate vocational evaluation, assessment, and counseling... program, as evidenced by empirical data from those programs, in such factors as— (i) Student performance... students in jobs, including military service; and (iv) Successful transfer of students to a variety of...

RNA editing-dependent epitranscriptome diversity in cancer stem cells

PubMed Central

Jiang, Qingfei; Crews, Leslie A.; Holm, Frida; Jamieson, Catriona H. M.

2017-01-01

Cancer stem cells (CSCs) can regenerate all facets of a tumour as a result of their stem cell-like capacity to self-renew, survive and become dormant in protective microenvironments. CSCs evolve during tumour progression in a manner that conforms to Charles Darwin’s principle of natural selection. Although somatic DNA mutations and epigenetic alterations promote evolution, post-transcriptional RNA modifications together with RNA binding protein activity (the ‘epitranscriptome’) might also contribute to clonal evolution through dynamic determination of RNA function and gene expression diversity in response to environmental stimuli. Deregulation of these epitranscriptomic events contributes to CSC generation and maintenance, which governs cancer progression and drug resistance. In this Review, we discuss the role of malignant RNA processing in CSC generation and maintenance, including mechanisms of RNA methylation, RNA editing and RNA splicing, and the functional consequences of their aberrant regulation in human malignancies. Finally, we highlight the potential of these events as novel CSC biomarkers as well as therapeutic targets. PMID:28416802

Detonation nanodiamond complexes with cancer stem cells inhibitors or paracrine products of mesenchymal stem cells as new potential medications

NASA Astrophysics Data System (ADS)

Konoplyannikov, A. G.; Alekseenskiy, A. E.; Zlotin, S. G.; Smirnov, B. B.; Kalsina, S. Sh.; Lepehina, L. A.; Semenkova, I. V.; Agaeva, E. V.; Baboyan, S. B.; Rjumshina, E. A.; Nosachenko, V. V.; Konoplyannikov, M. A.

2015-09-01

Combined use of complexes of the most active chemotherapeutic drugs and detonation nanodiamonds (DND) is a new trend in cancer therapy, which is probably related to selective chemotherapeutic drug delivery by DND to the zone of so-called cancer stem cells (CSC). Stable DND complexes of 4-5 nm size with salinomycin—a strong CSC inhibitor—have been obtained (as a suspension). It has been demonstrated that a complex administration considerably increases the drug antitumor effect on the transplantable tumor of LLC mice. A similar effect has been observed in CSC models in vivo, obtained by exposure of stem cells of normal mice tissues to a carcinogen 1,2-dimethylhydrazine. It has also been found out, that administration of DND complexes with the conditioned medium from mesenchymal stem cells (MSC) cultures to mice results in a considerable stimulation of stem cell pools in normal mice tissues, which can be used in regenerative medicine.

Multiplication free neural network for cancer stem cell detection in H-and-E stained liver images

NASA Astrophysics Data System (ADS)

Badawi, Diaa; Akhan, Ece; Mallah, Ma'en; Üner, Ayşegül; ćetin-Atalay, Rengül; ćetin, A. Enis

2017-05-01

Markers such as CD13 and CD133 have been used to identify Cancer Stem Cells (CSC) in various tissue images. It is highly likely that CSC nuclei appear as brown in CD13 stained liver tissue images. We observe that there is a high correlation between the ratio of brown to blue colored nuclei in CD13 images and the ratio between the dark blue to blue colored nuclei in H&E stained liver images. Therefore, we recommend that a pathologist observing many dark blue nuclei in an H&E stained tissue image may also order CD13 staining to estimate the CSC ratio. In this paper, we describe a computer vision method based on a neural network estimating the ratio of dark blue to blue colored nuclei in an H&E stained liver tissue image. The neural network structure is based on a multiplication free operator using only additions and sign operations. Experimental results are presented.

Golgi-localized STELLO proteins regulate the assembly and trafficking of cellulose synthase complexes in Arabidopsis

PubMed Central

Zhang, Yi; Nikolovski, Nino; Sorieul, Mathias; Vellosillo, Tamara; McFarlane, Heather E.; Dupree, Ray; Kesten, Christopher; Schneider, René; Driemeier, Carlos; Lathe, Rahul; Lampugnani, Edwin; Yu, Xiaolan; Ivakov, Alexander; Doblin, Monika S.; Mortimer, Jenny C.; Brown, Steven P.; Persson, Staffan; Dupree, Paul

2016-01-01

As the most abundant biopolymer on Earth, cellulose is a key structural component of the plant cell wall. Cellulose is produced at the plasma membrane by cellulose synthase (CesA) complexes (CSCs), which are assembled in the endomembrane system and trafficked to the plasma membrane. While several proteins that affect CesA activity have been identified, components that regulate CSC assembly and trafficking remain unknown. Here we show that STELLO1 and 2 are Golgi-localized proteins that can interact with CesAs and control cellulose quantity. In the absence of STELLO function, the spatial distribution within the Golgi, secretion and activity of the CSCs are impaired indicating a central role of the STELLO proteins in CSC assembly. Point mutations in the predicted catalytic domains of the STELLO proteins indicate that they are glycosyltransferases facing the Golgi lumen. Hence, we have uncovered proteins that regulate CSC assembly in the plant Golgi apparatus. PMID:27277162

Phase noise measurements with a cryogenic power-splitter to minimize the cross-spectral collapse effect

NASA Astrophysics Data System (ADS)

Hati, Archita; Nelson, Craig W.; Pappas, David P.; Howe, David A.

2017-11-01

The cross-spectrum noise measurement technique enables enhanced resolution of spectral measurements. However, it has disadvantages, namely, increased complexity, inability of making real-time measurements, and bias due to the "cross-spectral collapse" (CSC) effect. The CSC can occur when the spectral density of a random process under investigation approaches the thermal noise of the power splitter. This effect can severely bias results due to a differential measurement between the investigated noise and the anti-correlated (phase-inverted) noise of the power splitter. In this paper, we report an accurate measurement of the phase noise of a thermally limited electronic oscillator operating at room temperature (300 K) without significant CSC bias. We mitigated the problem by cooling the power splitter to liquid helium temperature (4 K). We quantify errors of greater than 1 dB that occur when the thermal noise of the oscillator at room temperature is measured with the power splitter at temperatures above 77 K.

Enhanced Depth SD-OCT Images Reveal Characteristic Choroidal Changes in Patients With Vogt-Koyanagi-Harada Disease.

PubMed

Li, Mei; Liu, Qiuhui; Luo, Yan; Li, Yonghao; Lin, Shaofen; Lian, Ping; Yang, Qiufen; Li, Xiaofang; Liu, Xialin; Sadda, SriniVas; Lu, Lin

2016-11-01

To identify characteristic choroidal changes of patients with Vogt-Koyanagi-Harada (VKH) disease at different stages. Fifty-four patients with VKH in the acute uveitic or convalescent stages, 24 patients with central serous chorioretinopathy (CSC), and 54 normal participants were enrolled in this prospective, observational study. Enhanced depth imaging spectral-domain optical coherence tomography scans were captured for all subjects to allow for comparison of choroidal morphological findings. Numerous round or oval hyperreflective profiles with hyporeflective cores, corresponding to choroidal vessels, were observed in the choroid of control participants and patients with CSC; whereas the numbers of these profiles were markedly decreased in the choroid of VKH patients in both the acute uveitic and convalescent stages. A reduction in vascular profiles in the choroid is observed in VKH and may aid in the differentiation with disorders such as CSC. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:1004-1012.]. Copyright 2016, SLACK Incorporated.

Oral epithelial stem cells – implications in normal development and cancer metastasis

PubMed Central

Papagerakis, Silvana; Pannone, Giuseppe; Zheng, Li; About, Imad; Taqi, Nawar; Nguyen, Nghia P.T.; Matossian, Margarite; McAlpin, Blake; Santoro, Angela; McHugh, Jonathan; Prince, Mark E.; Papagerakis, Petros

2014-01-01

Oral mucosa is continuously exposed to environmental forces and has to be constantly renewed. Accordingly, the oral mucosa epithelium contains a large reservoir of epithelial stem cells necessary for tissue homeostasis. Despite considerable scientific advances in stem cell behavior in a number of tissues, fewer studies have been devoted to the stem cells in the oral epithelium. Most of oral mucosa stem cells studies are focused on identifying cancer stem cells (CSC) in oral squamous cell carcinomas (OSCCs) among other head and neck cancers. OSCCs are the most prevalent epithelial tumors of the head and neck region, marked by their aggressiveness and invasiveness. Due to their highly tumorigenic properties, it has been suggested that CSC may be the critical population of cancer cells in the development of OSCC metastasis. This review presents a brief overview of epithelium stem cells with implications in oral health, and the clinical implications of the CSC concept in OSCC metastatic dissemination. PMID:24803391

[2.2.2]Paracyclophane as a receptor for the cesium cation in the gas phase

NASA Astrophysics Data System (ADS)

Makrlík, Emanuel; Sýkora, David; Böhm, Stanislav; Vaňura, Petr

2017-10-01

By using electrospray ionisation mass spectrometry, it was proven experimentally that the cesium cation (Cs+) forms with [2.2.2]paracyclophane (C24H24) the cationic complex [Cs(C24H24)]+. Further, applying quantum chemical calculations, the most probable structure of the [Cs(C24H24)]+ complex was derived. In the resulting complex with a symmetry very close to C3, the 'central' cation Cs+, fully located in the cavity of the parent [2.2.2]paracyclophane ligand, is bound to all three benzene rings of [2.2.2]paracyclophane via cation-π interaction. Finally, the interaction energy, E(int), of the considered cation-π complex [Cs(C24H24)]+ was found to be -73.2 kJ/mol, confirming the formation of this fascinating complex species as well. This means that [2.2.2]paracyclophane can be considered as a receptor for the Cs+ cation in the gas phase.

DNMT1 is essential for mammary and cancer stem cell maintenance and tumorigenesis.

PubMed

Pathania, Rajneesh; Ramachandran, Sabarish; Elangovan, Selvakumar; Padia, Ravi; Yang, Pengyi; Cinghu, Senthilkumar; Veeranan-Karmegam, Rajalakshmi; Arjunan, Pachiappan; Gnana-Prakasam, Jaya P; Sadanand, Fulzele; Pei, Lirong; Chang, Chang-Sheng; Choi, Jeong-Hyeon; Shi, Huidong; Manicassamy, Santhakumar; Prasad, Puttur D; Sharma, Suash; Ganapathy, Vadivel; Jothi, Raja; Thangaraju, Muthusamy

2015-04-24

Mammary stem/progenitor cells (MaSCs) maintain self-renewal of the mammary epithelium during puberty and pregnancy. DNA methylation provides a potential epigenetic mechanism for maintaining cellular memory during self-renewal. Although DNA methyltransferases (DNMTs) are dispensable for embryonic stem cell maintenance, their role in maintaining MaSCs and cancer stem cells (CSCs) in constantly replenishing mammary epithelium is unclear. Here we show that DNMT1 is indispensable for MaSC maintenance. Furthermore, we find that DNMT1 expression is elevated in mammary tumours, and mammary gland-specific DNMT1 deletion protects mice from mammary tumorigenesis by limiting the CSC pool. Through genome-scale methylation studies, we identify ISL1 as a direct DNMT1 target, hypermethylated and downregulated in mammary tumours and CSCs. DNMT inhibition or ISL1 expression in breast cancer cells limits CSC population. Altogether, our studies uncover an essential role for DNMT1 in MaSC and CSC maintenance and identify DNMT1-ISL1 axis as a potential therapeutic target for breast cancer treatment.

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

Karwacki, C.J.; Buchanan, J.H.; Mahle, J.J.

Experimental data are reported for the desorption of bis-2-chloroethyl sulfide, (a sulfur mustard or HD) and its decomposition products from activated coconut shell carbon (CSC). The results show that under equilibrium conditions changes in the HD partial pressure are affected primarily by its loading and temperature of the adsorbent. The partial pressure of adsorbed HD is found to increase by about a decade for each 25 C increase in temperature for CSC containing 0.01--0.1 g/g HD. Adsorption equilibria of HD appear to be little affected by coadsorbed water. Although complicated by its decomposition, the distribution of adsorbed HD (of knownmore » amount) appears to occupy pores of similar energy whether dry or in the presence of adsorbed water. On dry CSC adsorbed HD appears stable, while in the presence of water its decomposition is marked by hydrolysis at low temperature and thermal decomposition at elevated temperatures. The principal volatile products desorbed are 1,4-thioxane, 2-chloroethyl vinyl sulfide and 1,4-dithiane, with the latter favoring elevated temperatures.« less

Rerouting Success: Several Academic Pathways Programs Are Fueling Reform at Community Colleges

ERIC Educational Resources Information Center

Woods, Bob

2015-01-01

"Completion" has become the rallying cry at community colleges. As the 21st century unfolds, the earlier emphasis on guaranteeing greater access to a postsecondary education has evolved into a sharp focus on student success. Whether that means earning a workforcerelated certificate or an associate degree transferable to a four-year…

Correlation between fundus autofluorescence and central visual function in chronic central serous chorioretinopathy.

PubMed

Eandi, Chiara M; Piccolino, Felice Cardillo; Alovisi, Camilla; Tridico, Federico; Giacomello, Daniela; Grignolo, Federico M

2015-04-01

To find possible correlations between the morphologic macular changes revealed by fundus autofluorescence (FAF) and the functional parameters such as visual acuity and retinal sensitivity in patients with chronic central serous chorioretinopathy (CSC). Prospective, cross-sectional study. Forty-six eyes (39 consecutive patients) with chronic CSC were studied with FAF and microperimetry (MP). Retinal sensitivity value maps were exactly superimposed over FAF images. The following microperimetric parameters were applied: central 10-degree visual field, 4-2-1 strategy, 61 stimulation spots, white monochromatic background, stimulation time 200 ms, stimulation spot size Goldmann III. A possible relationship between MP and FAF was investigated. Mean best-corrected visual acuity (BCVA) was 20/32 (median 20/25, range 20/20-20/200). BCVA was significantly correlated with FAF findings (Mann-Whitney test; P < .0001). A positive concordance between FAF and MP evaluation was also found (total concordance of 0.720 with a kappa of Cohen of 0.456). The hypo-autofluorescent areas showed decreased retinal sensitivity, while adjacent areas of increased FAF could be associated to both normal and decreased retinal sensitivity. Absolute scotoma, defined as 0 dB retinal sensitivity, corresponded with absence of autofluorescence. Altered FAF in chronic CSC patients has a functional correlation quantified by microperimetry. This study confirms the impact of FAF changes on retinal sensitivity and their value to reflect the functional impairment in chronic CSC. Copyright © 2015 Elsevier Inc. All rights reserved.

Optimized dosing schedule based on circadian dynamics of mouse breast cancer stem cells improves the anti-tumor effects of aldehyde dehydrogenase.

PubMed

Matsunaga, Naoya; Ogino, Takashi; Hara, Yukinori; Tanaka, Takahiro; Koyanagi, Satoru; Ohdo, Shigehiro

2018-05-07

Although malignant phenotypes of triple-negative breast cancer (TNBC) are subject to circadian alterations, the role of cancer stem cells (CSC) in defining this circadian change remains unclear. CSC are often characterized by high aldehyde dehydrogenase (ALDH) activity, which is associated with the malignancy of cancer cells and used for identification and isolation of CSC. Here we show that the popultation of ALDH-positive cells in a mouse 4T1 breast tumor model exhibits pronounced circadian alterations. Alterations in the number of ALDH-positive cells was generated by time-dependent increases and decreases in the expression of Aldh3a1. Importantly, circadian clock genes were rhythmically expressed in ALDH-negative cells, but not in ALDH-positive cells. Circadian expression of Aldh3a1 in ALDH-positive cells was dependent on the time-dependent release of Wingless-type mmtv integration site family 10a (WNT10a) from ALDH-negative cells. Furthermore, anti-tumor and anti-metastatic effects of ALDH inhibitor N,N-diethylaminobenzaldehyde were enhanced by administration at the time of day when ALDH activity was increased in 4T1 tumor cells. Our findings reveal a new role for the circadian clock within the tumor microenvironment in regulating the circadian dynamics of CSC. These results should enable the development of novel therapeutic strategies for treatment of TNBC with ALDH inhibitors. Copyright ©2018, American Association for Cancer Research.

Cancer stem cells in head and neck squamous cell carcinoma: a review.

PubMed

Satpute, Pranali Shirish; Hazarey, Vinay; Ahmed, Riyaz; Yadav, Lalita

2013-01-01

Research indicates that a small population of cancer cells is highly tumorigenic, endowed with the capacity for self-renewal, and has the ability to differentiate into cells that constitute the bulk of tumors. These cells are considered the "drivers" of the tumorigenic process in some tumor types, and have been named cancer stem cells (CSC). Epithelial-mesenchymal transition (EMT) appears to be involved in the process leading to the acquisition of stemness by epithelial tumor cells. Through this process, cells acquire an invasive phenotype that may contribute to tumor recurrence and metastasis. CSC have been identified in human head and neck squamous cell carcinomas (HNSCC) using markers such as CD133 and CD44 expression, and aldehyde dehydrogenase (ALDH) activity. Head and neck cancer stem cells reside primarily in perivascular niches in the invasive fronts where endothelial-cell initiated events contribute to their survival and function. Clinically, CSC enrichment has been shown to be enhanced in recurrent disease, treatment failure and metastasis. CSC represent a novel target of study given their slow growth and innate mechanisms conferring treatment resistance. Further understanding of their unique phenotype may reveal potential molecular targets to improve therapeutic and survival outcomes in patients with HNSCC. Here, we discuss the state-of-the-knowledge on the pathobiology of cancer stem cells, with a focus on the impact of these cells on head and neck tumor progression, metastasis and recurrence due to treatment failure.

Cancer stem cells (CSCs), cervical CSCs and targeted therapies.

PubMed

Huang, Ruixia; Rofstad, Einar K

2017-05-23

Accumulating evidence has shown that cancer stem cells (CSCs) have a tumour-initiating capacity and play crucial roles in tumour metastasis, relapse and chemo/radio-resistance. As tumour propagation initiators, CSCs are considered to be promising targets for obtaining a better therapeutic outcome. Cervical carcinoma is the most common gynaecological malignancy and has a high cancer mortality rate among females. As a result, the investigation of cervical cancer stem cells (CCSCs) is of great value. However, the numbers of cancer cells and corresponding CSCs in malignancy are dynamically balanced, and CSCs may reside in the CSC niche, about which little is known to date. Therefore, due to their complicated molecular phenotypes and biological behaviours, it remains challenging to obtain "purified" CSCs and continuously culture CSCs for further in vitro studies without the cells losing their stem properties. At present, CSC-related markers and functional assays are used to purify, identify and therapeutically target CSCs both in vitro and in vivo. Nevertheless, CSC-related markers are not universal to all tumour types, although some markers may be valid in multiple tumour types. Additionally, functional identifications based on CSC-specific properties are usually limited in in vivo studies. Furthermore, an optimal method for identifying potential CCSCs in CCSC studies has not been previously published, and these techniques are currently of great importance. This article updates our knowledge on CSCs and CCSCs, reviews potential stem cell markers and functional assays for identifying CCSCs, and describes the potential of targeting CCSCs in the treatment of cervical carcinoma.

Treatment Analysis in a Cancer Stem Cell Context Using a Tumor Growth Model Based on Cellular Automata.

PubMed

Monteagudo, Ángel; Santos, José

2015-01-01

Cancer can be viewed as an emergent behavior in terms of complex system theory and artificial life, Cellular Automata (CA) being the tool most used for studying and characterizing the emergent behavior. Different approaches with CA models were used to model cancer growth. The use of the abstract model of acquired cancer hallmarks permits the direct modeling at cellular level, where a cellular automaton defines the mitotic and apoptotic behavior of cells, and allows for an analysis of different dynamics of the cellular system depending on the presence of the different hallmarks. A CA model based on the presence of hallmarks in the cells, which includes a simulation of the behavior of Cancer Stem Cells (CSC) and their implications for the resultant growth behavior of the multicellular system, was employed. This modeling of cancer growth, in the avascular phase, was employed to analyze the effect of cancer treatments in a cancer stem cell context. The model clearly explains why, after treatment against non-stem cancer cells, the regrowth capability of CSCs generates a faster regrowth of tumor behavior, and also shows that a continuous low-intensity treatment does not favor CSC proliferation and differentiation, thereby allowing an unproblematic control of future tumor regrowth. The analysis performed indicates that, contrary to the current attempts at CSC control, trying to make CSC proliferation more difficult is an important point to consider, especially in the immediate period after a standard treatment for controlling non-stem cancer cell proliferation.

Treatment of ovarian cancer by targeting the tumor stem cell-associated carbohydrate antigen, Sialyl-Thomsen-nouveau.

PubMed

Starbuck, Kristen; Al-Alem, Linah; Eavarone, David A; Hernandez, Silvia Fatima; Bellio, Chiara; Prendergast, Jillian M; Stein, Jenna; Dransfield, Daniel T; Zarrella, Bianca; Growdon, Whitfield B; Behrens, Jeff; Foster, Rosemary; Rueda, Bo R

2018-05-01

Recurrent ovarian cancer (OvCa) is thought to result in part from the inability to eliminate rare quiescent cancer stem cells (CSCs) that survive cytotoxic chemotherapy and drive tumor resurgence. The Sialyl-Thomsen-nouveau antigen (STn) is a carbohydrate moiety present on protein markers of CSCs in pancreatic, colon, and gastric malignancies. We have demonstrated that human OvCa cell lines contain varying levels of cells that independently express either STn or the ovarian CSC marker CD133. Here we determine co-expression of STn and CD133 in a subset of human OvCa cell lines. Analyses of colony and sphere forming capacity and of response to standard-of-care cytotoxic therapy suggest a subset of OvCa STn + cells display some CSC features. The effect of the anti-STn antibody-drug conjugates (ADCs) S3F-CL-MMAE and 2G12-2B2-CL-MMAE on OvCa cell viability in vitro and in vivo was also assessed. Treatment with S3F-CL-MMAE reduced the viability of two of three OvCa cell lines in vitro and exposure to either S3F-CL-MMAE or 2G12-2B2-CL-MMAE reduced OVCAR3-derived xenograft volume in vivo , depleting STn + tumor cells. In summary, STn + cells demonstrate some stem-like properties and specific therapeutic targeting of STn in ovarian tumors may be an effective clinical strategy to eliminate both STn + CSC and STn + non-CSC populations.

Effect of Wasabi Component 6-(Methylsulfinyl)hexyl Isothiocyanate and Derivatives on Human Pancreatic Cancer Cells

PubMed Central

Chen, Yu-Jen; Huang, Yu-Chuen; Tsai, Tung-Hu

2014-01-01

The naturally occurring compound 6-(methylsulfinyl)hexyl isothiocyanate (6-MITC) was isolated from Wasabia japonica (Wasabi), a pungent spice used in Japanese food worldwide. The synthetic derivatives 6-(methylsulfenyl)hexyl isothiocyanate (I7447) and 6-(methylsulfonyl)hexyl isothiocyanate (I7557) are small molecule compounds derived from 6-MITC. This study aimed to evaluate the effect of these compounds on human pancreatic cancer cells. Human pancreatic cancer cell lines PANC-1 and BxPC-3 were used to perform an MTT assay for cell viability and Liu's stain for morphological observation. The cell cycle was analyzed by DNA histogram. Aldehyde dehydrogenase (ALDH) activity was used as a marker for cancer stem cells (CSC). Western blotting was performed for the expression of proteins related to CSC signaling. The results showed that compounds 6-MITC and I7557, but not I7447, inhibited viability of both PANC-1 and BxPC-3 cells. Morphological observation showed mitotic arrest and apoptosis in 6-MITC- and I7557-treated cells. These two compounds induced G2/M phase arrest and hypoploid population. Percentages of ALDH-positive PANC-1 cells were markedly reduced by 6-MITC and I7557 treatment. The expression of CSC signaling molecule SOX2, but not NOTCH1, ABCG2, Sonic hedgehog, or OCT4, was inhibited by 6-MITC and I7557. In conclusion, wasabi compounds 6-MITC and I7557 may possess activity against the growth and CSC phenotypes of human pancreatic cancer cells. PMID:24575144

Effect of Wasabi Component 6-(Methylsulfinyl)hexyl Isothiocyanate and Derivatives on Human Pancreatic Cancer Cells.

PubMed

Chen, Yu-Jen; Huang, Yu-Chuen; Tsai, Tung-Hu; Liao, Hui-Fen

2014-01-01

The naturally occurring compound 6-(methylsulfinyl)hexyl isothiocyanate (6-MITC) was isolated from Wasabia japonica (Wasabi), a pungent spice used in Japanese food worldwide. The synthetic derivatives 6-(methylsulfenyl)hexyl isothiocyanate (I7447) and 6-(methylsulfonyl)hexyl isothiocyanate (I7557) are small molecule compounds derived from 6-MITC. This study aimed to evaluate the effect of these compounds on human pancreatic cancer cells. Human pancreatic cancer cell lines PANC-1 and BxPC-3 were used to perform an MTT assay for cell viability and Liu's stain for morphological observation. The cell cycle was analyzed by DNA histogram. Aldehyde dehydrogenase (ALDH) activity was used as a marker for cancer stem cells (CSC). Western blotting was performed for the expression of proteins related to CSC signaling. The results showed that compounds 6-MITC and I7557, but not I7447, inhibited viability of both PANC-1 and BxPC-3 cells. Morphological observation showed mitotic arrest and apoptosis in 6-MITC- and I7557-treated cells. These two compounds induced G2/M phase arrest and hypoploid population. Percentages of ALDH-positive PANC-1 cells were markedly reduced by 6-MITC and I7557 treatment. The expression of CSC signaling molecule SOX2, but not NOTCH1, ABCG2, Sonic hedgehog, or OCT4, was inhibited by 6-MITC and I7557. In conclusion, wasabi compounds 6-MITC and I7557 may possess activity against the growth and CSC phenotypes of human pancreatic cancer cells.

PRESENTATION OF CENTRAL SEROUS CHORIORETINOPATHY IN TWO HUSBAND AND WIFE COUPLES.

PubMed

Kanesa-Thasan, Aditya; Fawzi, Amani A; Gill, Manjot K

2018-01-01

Central serous chorioretinopathy (CSC) is a disease in which serous detachment of the neurosensory retina occurs over an area of leakage from the choriocapillaris through the retinal pigment epithelium. Associations have been drawn between high-stress personality types and steroid exposure. This article aims to describe a unique case series of two husband and wife couples with CSC. All methods were approved by the authors' institution's institutional review board. History, physical examination, and imaging data were obtained from the electronic medical records of the patients in question and from the providers who cared for these patients. Couple 1: A 35-year-old man presented with "dark spots" in his right eye. He reported no recent steroid use. Visual acuity at presentation was 20/30 in the right eye and 20/20 in the left eye. On fundus examination, there was subretinal fluid in the right eye. His wife presented on the same day with a "wavy section" in the right eye for 6 weeks. She also had no recent steroid use. Visual acuity at presentation was 20/20 in both eyes with blunting of the foveal reflex in the right eye. Optical coherence tomography showed a thick choroid with a pigment epithelial detachment in the right eye. Couple 2: A 34-year-old man presented with "blurry vision" in his right eye for one month. He was taking oral and nasal steroids for chronic sinusitis. Visual acuity was 20/30 in the right eye and 20/20 in the left eye. Fluorescein angiography and indocyanine green confirmed the diagnosis of CSC. After 3 months of persistent subretinal fluid, he received photodynamic therapy in the right eye. Three days after his photodynamic therapy, his 38-year-old wife presented with subjective blurring in both eyes. Visual acuity was 20/20 in both eyes, but optical coherence tomography showed thick choroid in both eyes, a large central pigment epithelial detachment in the right eye, and 3 small pigment epithelial detachments in the left eye. She had no history of steroid use but did admit to high stress recently. All the patients in this case series were diagnosed with CSC. This is the first series to describe the simultaneous occurrence of CSC in spouses. Possible explanations for these presentations may include shared external stressors or secondary steroid exposure. Clinicians may consider inquiring about family members or cohabitants with similar symptoms if CSC is suspected.

Theory of gastric CO2 ventilation and its control during respiratory acidosis: implications for central chemosensitivity, pH regulation, and diseases causing chronic CO2 retention.

PubMed

Dean, Jay B

2011-02-15

The theory of gastric CO(2) ventilation describes a previously unrecognized reflex mechanism controlled by neurons in the caudal solitary complex (cSC) for non-alveolar elimination of systemic CO(2) during respiratory acidosis. Neurons in the cSC, which is a site of CO(2) chemosensitivity for cardiorespiratory control, also control various gastroesophageal reflexes that remove CO(2) from blood. CO(2) is consumed in the production of gastric acid and bicarbonate in the gastric epithelium and then reconstituted as CO(2) in the stomach lumen from the reaction between H(+) and HCO(3)(-). Respiratory acidosis and gastric CO(2) distension induce cSC/vagovagal mediated transient relaxations of the lower esophageal sphincter to vent gastric CO(2) upwards by bulk flow along an abdominal-to-esophageal (=intrapleural) pressure gradient the magnitude of which increases during abdominal (gastric) compression caused by increased contractions of respiratory muscles. Esophageal distension induces cSC/nucleus ambiguus/vagovagal reflex relaxation of the upper esophageal sphincter and CO(2) is vented into the pharynx and mixed with pulmonary gas during expiration or, alternatively, during eructation. It is proposed that gastric CO(2) ventilation provides explanations for (1) the postprandial increase in expired CO(2) and (2) the negative P(blood - expired)CO₂difference that occurs with increased inspired CO(2). Furthermore, it is postulated that gastric CO(2) ventilation and alveolar CO(2) ventilation are coordinated under dual control by CO(2) chemosensitive neurons in the cSC. This new theory, therefore, presupposes a level of neural control and coordination between two previously presumed dissimilar organ systems and supports the notion that different sites of CO(2) chemosensitivity address different aspects of whole body pH regulation. Consequently, not all sites of central chemosensitivity are equal regarding the mechanism(s) activated for CO(2) elimination. A distributed CO(2) chemosensitive network-at least nine different areas in the CNS, including the cSC, have been reported to date-may reflect the complexity and dynamic nature of the fundamental neural circuitry required to achieve CO(2)/pH regulation across multiple organ systems under various states of arousal, oxygenation, pH status, and redox state. Moreover, coordination of respiratory and digestive control networks through the cSC could also account for the frequent co-expression of pulmonary diseases that cause chronic respiratory acidosis (and overstimulation of cSC neurons) with peptic ulcer disease or gastroesophageal reflux disease. Copyright © 2010 Elsevier B.V. All rights reserved.

The Goddard High Resolution Spectrograph Scientific Support Contract

NASA Technical Reports Server (NTRS)

1997-01-01

In 1988, Computer Sciences Corporation (CSC) was selected as the Goddard High Resolution Spectrograph (GHRS) Scientific Support Contractor (SSC). This was to have been a few months before the launch of NASA's first Great Observatory, the Hubble Space Telescope (HST). As one of five scientific instruments on HST, the GHRS was designed to obtain spectra in the 1050-3300 A ultraviolet wavelength region with a resolving power, lambda/Delta(lambda) , of up to 100,000 and relative photometric accuracy to 1%. It was built by Ball AeroSpace Systems Group under the guidance of the GHRS Investigation Definition Team (IDT), comprised of 16 scientists from the US and Canada. After launch, the IDT was to perform the initial instrument calibration and execute a broad scientific program during a five-year Guaranteed Time Observation (GTO) period. After a year's delay, the launch of HST occurred in April 1990, and CSC participated in the in-orbit calibration and first four years of GTO observations with the IDT. The HST primary mirror suffered from spherical aberration, which reduced the spatial and spectral resolution of Large Science Aperture (LSA) observations and decreased the throughput of the Small Science Aperture (SSA) by a factor of two. Periodic problems with the Side 1 carrousel electronics and anomalies with the low-voltage power supply finally resulted in a suspension of the use of Side 1 less than two years after launch. At the outset, the GHRS SSC task involved work in four areas: 1) to manage and operate the GHRS Data Analysis Facility (DAF); 2) to support the second Servicing Mission Observatory Verification (SMOV) program, as well as perform system engineering analysis of the GHRS as nesessary; 3) to assist the GHRS IDT with their scientific research programs, particularly the GSFC members of the team, and 4) to provide administrative and logistic support for GHRS public information and educational activities.

Partnering for Success: A 21st Century Model for Teacher Preparation

ERIC Educational Resources Information Center

Kennedy, Kathryn, Ed.; Archambault, Leanna, Ed.

2013-01-01

This report studies the best practices necessary to rethink the skills, methods, and pedagogical evolution that teacher education must address. If we are to ensure great teachers are trained, mentored, and retained for our students--the programs themselves must emulate 21st century skills. The examples found in this report have unique elements and…

UPLC-MS/MS method for the determination of tobacco-specific biomarker NNAL, tamoxifen and its main metabolites in rat plasma.

PubMed

Xiong, Wei; Zhao, Jiajia; Wang, Ling; Jiang, Xuehua

2017-06-01

Cigarette smoke is known to interact with tamoxifen-metabolizing enzymes and transporters and potentially affect its treatment outcome. 4-(N-nitrosomethylamino)-1-(3-pyridyl)-1-butanol (NNAL) is an important metabolite of 4-(methylnitro-samino)-1-(3-pyridyl)-1-butanone (NNK) because it is frequently used as a biomarker to assess human smoke exposure. In order to study the potential pharmacokinetic interaction between cigarette smoke and tamoxifen in rats a UPLC-MS/MS method for the simultaneous determination of NNAL and tamoxifen along with its metabolites in rat plasma has been developed and validated. Analytes were extracted with methanol and separated on a HSS T3 column by a gradient elution with the mobile phase consisting of acetonitrile and water. The lower limits of quantitation ranged from 0.05 to 0.62 ng/mL. Precisions showed RSD <15.8% and accuracy in the range 80.6-116.0%. Mean analyte recoveries ranged from 76.9 to 108.4%. The method was successfully applied to study the effects of cigarette smoke condensate (CSC), NNK and benzo(a)pyrene pre-treatment on the pharmacokinetics of tamoxifen and its metabolites in rats. Significant effects of CSC, NNK, benzo(a)pyrene were observed on pharmacokinetics of tamoxifen and its metabolites. We also found that plasma NNAL levels are statistically significant correlated with plasma 4-hydroxy-tamoxifen and endoxifen. Copyright © 2016 John Wiley & Sons, Ltd.

Metafile for Interactive Documents. Version 2.0. Application Guide and Draft Performance Specification for the Encoding of Interactive Documents.

DTIC Science & Technology

1996-03-01

Darlene Janiszewski, NAWC-AD, Project Manager L. John Junod , NSWC-CD Michael Anderson, Antech Systems, Editor and Team Chairman David Cooper, Antech...Michael Croswell, CSC Mark Drissel, CSC Rob Groat, Booz Allen Eric Jorgensen, NSWC Carderock L. John Junod , NSWC Carderock Neill Kipp, TechnoTeacher Steve...contact Mr. John Junod at < junod @oasys.dt.navy.mil>. 1 MID-2 (3/96) 2.2.3 MID Design & Development Team Members The MID Design Team was formed in

The neural and computational bases of semantic cognition.

PubMed

Ralph, Matthew A Lambon; Jefferies, Elizabeth; Patterson, Karalyn; Rogers, Timothy T

2017-01-01

Semantic cognition refers to our ability to use, manipulate and generalize knowledge that is acquired over the lifespan to support innumerable verbal and non-verbal behaviours. This Review summarizes key findings and issues arising from a decade of research into the neurocognitive and neurocomputational underpinnings of this ability, leading to a new framework that we term controlled semantic cognition (CSC). CSC offers solutions to long-standing queries in philosophy and cognitive science, and yields a convergent framework for understanding the neural and computational bases of healthy semantic cognition and its dysfunction in brain disorders.

Cancer Stem Cell Radioresistance and Enrichment: Where Frontline Radiation Therapy May Fail in Lung and Esophageal Cancers

PubMed Central

Nguyen, Giang Huong; Murph, Mandi M.; Chang, Joe Y.

2011-01-01

Many studies have highlighted the role cancer stem cells (CSC) play in the development and progression of various types of cancer including lung and esophageal cancer. More recently, it has been proposed that the presence of CSCs affects treatment efficacy and patient prognosis. In reviewing this new area of cancer biology, we will give an overview of the current literature regarding lung and esophageal CSCs and radioresistance of CSC, and discuss the potential therapeutic applications of these findings. PMID:21603589

From Survival to Success: Promoting Minority Student Retention. Monograph Series Volume 9.

ERIC Educational Resources Information Center

Terrell, Melvin C., Ed.; Wright Doris J., Ed.

This monograph presents issues regarding minority student retention in higher education stressing the commitment of successful programs to campuswide cultural diversity as well as the importance of helping these students compete and succeed in the high tech world of the 21st century. In Chapter One, "Minority Student Retention: A Moral and…

38 CFR 21.5100 - Counseling.

Code of Federal Regulations, 2010 CFR

2010-07-01

... is met when— (i) The veteran has had one or more personal interviews with the counselor; (ii) The... personal problems which are likely to interfere with the successful pursuit of a program. (b) Availability...

Constructing 21st-Century Teacher Education

ERIC Educational Resources Information Center

Darling-Hammond, Linda

2006-01-01

Much of what teachers need to know to be successful is invisible to lay observers, leading to the view that teaching requires little formal study and to frequent disdain for teacher education programs. The weakness of traditional program models that are collections of largely unrelated courses reinforce this low regard. This article argues that we…

Results of the 1982 NASA/JPL balloon flight solar cell calibration program

NASA Technical Reports Server (NTRS)

Downing, R. G.; Weiss, R. S.

1983-01-01

The 1982 solar cell calibration balloon flight was successfully completed on July 21, meeting all objectives of the program. Twenty-eight modules were carried to an altitude of 36.0 kilometers. The calibrated cells can now be used as reference standards in simulator testing of cells and arrays.

Certified Staffing: A Formula for Success

ERIC Educational Resources Information Center

Thompson, Martina M.

2005-01-01

For the past three years, five Topeka-area schools have participated in the Topeka Academy for Leading Learners program, or TALL. A 21st Century Community Learning Center Project funded by the U.S. Department of Education and the Mott Foundation, TALL serves approximately 300 students through an after-school program in four elementary schools and…

Analysis of Selected Factors Relating to the Neighborhood Youth Corps Out of School Program in Rural Counties of Oregon.

ERIC Educational Resources Information Center

Bigsby, Robert A.; Clark, Harry E.

The Neighborhood Youth Corps Out-of-School Program in 27 Oregon counties was studied (1) to assess the effectiveness of the program in aiding enrollees (school dropouts aged 16-21) to obtain productive jobs and/or to continue their education and (2) to identify socioeconomic and educational factors associated with success or failure in the…

Small-Molecule ONC201/TIC10 Targets Chemotherapy-Resistant Colorectal Cancer Stem-like Cells in an Akt/Foxo3a/TRAIL-Dependent Manner.

PubMed

Prabhu, Varun V; Allen, Joshua E; Dicker, David T; El-Deiry, Wafik S

2015-04-01

Self-renewing colorectal cancer stem/progenitor cells (CSC) contribute to tumor maintenance and resistance to therapy. Therapeutic targeting of CSCs could improve treatment response and prolong patient survival. ONC201/TIC10 is a first-in-class antitumor agent that induces TRAIL pathway-mediated cell death in cancer cells without observed toxicity. We have previously described that ONC201/TIC10 exposure leads to transcriptional induction of the TRAIL gene via transcription factor Foxo3a, which is activated by dual inactivation of Akt and ERK. The Akt and ERK pathways serve as important targets in CSCs. Foxo3a is a key mediator of Akt and ERK-mediated CSC regulation. We hypothesized that the potent antitumor effect of ONC201/TIC10 in colorectal cancer involves targeting CSCs and bulk tumor cells. ONC201/TIC10 depletes CD133(+), CD44(+), and Aldefluor(+) cells in vitro and in vivo. TIC10 significantly inhibits colonosphere formation of unsorted and sorted 5-fluorouracil-resistant CSCs. ONC201/TIC10 significantly reduces CSC-initiated xenograft tumor growth in mice and prevents the passage of these tumors. ONC201/TIC10 treatment also decreased xenograft tumor initiation and was superior to 5-fluorouracil treatment. Thus, ONC201/TIC10 inhibits CSC self-renewal in vitro and in vivo. ONC201/TIC10 inhibits Akt and ERK, consequently activating Foxo3a and significantly induces cell surface TRAIL and DR5 expression in both CSCs and non-CSCs. ONC201/TIC10-mediated anti-CSC effect is significantly blocked by the TRAIL sequestering antibody RIK-2. Overexpression of Akt, DR5 knockdown, and Foxo3a knockdown rescues ONC201/TIC10-mediated depletion of CD44(+) cells and colonosphere inhibition. In conclusion, ONC201/TIC10 is a promising agent for colorectal cancer therapy that targets both non-CSCs and CSCs in an Akt-Foxo3a-TRAIL-dependent manner. ©2015 American Association for Cancer Research.

In vitro and in vivo antiproliferative activity of metformin on stem-like cells isolated from spontaneous canine mammary carcinomas: translational implications for human tumors.

PubMed

Barbieri, Federica; Thellung, Stefano; Ratto, Alessandra; Carra, Elisa; Marini, Valeria; Fucile, Carmen; Bajetto, Adriana; Pattarozzi, Alessandra; Würth, Roberto; Gatti, Monica; Campanella, Chiara; Vito, Guendalina; Mattioli, Francesca; Pagano, Aldo; Daga, Antonio; Ferrari, Angelo; Florio, Tullio

2015-04-07

Cancer stem cells (CSCs) are considered the cell subpopulation responsible for breast cancer (BC) initiation, growth, and relapse. CSCs are identified as self-renewing and tumor-initiating cells, conferring resistance to chemo- and radio-therapy to several neoplasias. Nowadays, th (about 10mM)e pharmacological targeting of CSCs is considered an ineludible therapeutic goal. The antidiabetic drug metformin was reported to suppress in vitro and in vivo CSC survival in different tumors and, in particular, in BC preclinical models. However, few studies are available on primary CSC cultures derived from human postsurgical BC samples, likely because of the limited amount of tissue available after surgery. In this context, comparative oncology is acquiring a relevant role in cancer research, allowing the analysis of larger samples from spontaneous pet tumors that represent optimal models for human cancer. Isolation of primary canine mammary carcinoma (CMC) cells and enrichment in stem-like cell was carried out from fresh tumor specimens by culturing cells in stem-permissive conditions. Phenotypic and functional characterization of CMC-derived stem cells was performed in vitro, by assessment of self-renewal, long-lasting proliferation, marker expression, and drug sensitivity, and in vivo, by tumorigenicity experiments. Corresponding cultures of differentiated CMC cells were used as internal reference. Metformin efficacy on CMC stem cell viability was analyzed both in vitro and in vivo. We identified a subpopulation of CMC cells showing human breast CSC features, including expression of specific markers (i.e. CD44, CXCR4), growth as mammospheres, and tumor-initiation in mice. These cells show resistance to doxorubicin but were highly sensitive to metformin in vitro. Finally, in vivo metformin administration significantly impaired CMC growth in NOD-SCID mice, associated with a significant depletion of CSCs. Similarly to the human counterpart, CMCs contain stem-like subpopulations representing, in a comparative oncology context, a valuable translational model for human BC, and, in particular, to predict the efficacy of antitumor drugs. Moreover, metformin represents a potential CSC-selective drug for BC, as effective (neo-)adjuvant therapy to eradicate CSC in mammary carcinomas of humans and animals.

The sonic hedgehog signaling pathway maintains the cancer stem cell self-renewal of anaplastic thyroid cancer by inducing snail expression.

PubMed

Heiden, Katherine B; Williamson, Ashley J; Doscas, Michelle E; Ye, Jin; Wang, Yimin; Liu, Dingxie; Xing, Mingzhao; Prinz, Richard A; Xu, Xiulong

2014-11-01

Cancer stem cells (CSCs) have been recently identified in thyroid neoplasm. Anaplastic thyroid cancer (ATC) contains a higher percentage of CSCs than well-differentiated thyroid cancer. The signaling pathways and the transcription factors that regulate thyroid CSC self-renewal remain poorly understood. The objective of this study is to use two ATC cell lines (KAT-18 and SW1736) as a model to study the role of the sonic hedgehog (Shh) pathway in maintaining thyroid CSC self-renewal and to understand its underlying molecular mechanisms. The expression and activity of aldehyde dehydrogenase (ALDH), a marker for thyroid CSCs, was analyzed by Western blot and ALDEFLUOR assay, respectively. The effect of three Shh pathway inhibitors (cyclopamine, HhAntag, GANT61), Shh, Gli1, Snail knockdown, and Gli1 overexpression on thyroid CSC self-renewal was analyzed by ALDEFLUOR assay and thyrosphere formation. The sensitivity of transfected KAT-18 cells to radiation was evaluated by a colony survival assay. Western blot analysis revealed that ALDH protein levels in five thyroid cancer cell lines (WRO82, a follicular thyroid cancer cell line; BCPAP and TPC1, two papillary thyroid cancer cell lines; KAT-18 and SW1736, two ATC cell lines) correlated with the percentage of the ALDH(High) cells as well as Gli1 and Snail expression. The Shh pathway inhibitors, Shh and Gli1 knockdown, in KAT-18 cells decreased thyroid CSC self-renewal and increased radiation sensitivity. In contrast, Gli1 overexpression led to increased thyrosphere formation, an increased percentage of ALDH(High) cells, and increased radiation resistance in KAT-18 cells. Inhibition of the Shh pathway by three specific inhibitors led to decreased Snail expression and a decreased number of ALDH(High) cells in KAT-18 and SW1736. Snail gene knockdown decreased the number of ALDH(High) cells in KAT-18 and SW1736 cells. The Shh pathway promotes the CSC self-renewal in ATC cell lines by Gli1-induced Snail expression.

Radionuclides in milk of dairy heifers raised on forages harvested from phosphatic clay soils on reclaimed mined land

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

Staples, C.R.; Umana, R.; Hayen, M.J.

1994-07-01

Alfalfa (AR; Medicago sativa L.) and corn (CSR; Zea mays L.) were grown in phosphatic clay soils on phosphate-mined reclaimed land in central Florida. Corn (CSC) also was grown on unmined land and served as a control forage. Upon harvesting, plants were chopped and ensiled. Concentrations of {sup 226}Ra averaged 2.44, 0.26 and 0.15; {sup 210}Pb averaged 1.04, 0.63, and 0.52; and {sup 210}Po averaged 1.59, 0.59, and 1.26 Bq kg{sup -1} DM for AR, CSR, and CSC, respectively. These forages were fed separately to Holstein dairy replacement heifers (Bos taurus) (n=15 per forage) from approximately 9 to 25 momore » of age. Heifers gave birth to calves at approximately 24 mo of age. Samples of milk were collected on d 1, 15, and 30 of lactation and analyzed for radionuclides. Averaged across sampling days, heifers fed AR had greater milk concentrations of {sup 226}Ra compared with those fed CSR (0.27 vs. 0.22 Bq kg{sup -1} DM; P < 0.10), which, in turn, had greater milk concentrations compared with heifers fed CSC (0.22 vs. 0.13 Bq kg{sup -1} DM; P < 0.05). Heifers fed AR also had greater milk concentrations of {sup 210}Po compared with heifers fed CSR (0.58 vs. 0.30 Bq kg{sup -1} DM; P < 0.10), but values of CSR-fed heifers were not different from CSC-fed heifers (0.45 Bq kg{sup -1} DM). Lead-210 was greater in milk from heifers fed CSR compared with those fed AR or CSC (1.38 vs. 0.94 and 0.92 Bq kg{sup -1} DM; P < 0.13), respectively. Plasma S and Cu concentrations suggested subclinical molybdenosis in heifers fed AR. However, all heifers grew at an acceptable rate, conceived normally, had normal gestation periods, gave high quality colostrum at calving, and produced similar amounts of milk. 17 refs., 9 tabs.« less

Smokestack leak in central serous chorioretinopathy.

PubMed

Bujarborua, Dhiren; Nagpal, Pran N; Deka, Manab

2010-03-01

To study the demography, various morphological patterns and fluid dynamics of the smokestack leak by fluorescein angiography (FA) in central serous chorioretinopathy (CSC). Part I (clinical): review of the medical records and angiographic documents of 69 consecutive cases of CSC with smokestack leak. Part II (experimental): documentation of the movement of various concentrations of fluorescein dye due to convection currents in a laboratory model that roughly represents a closed chamber similar to that of CSC in human eyes. The clinical study (Part I) revealed that 14.40% of 479 consecutive cases had smokestack leak, of which 70% occurred in first acute episode (p-value: <0.001), 27.14% in acute recurrent episodes (50% fresh leak) and 2.85% in chronic stage. Patients were predominantly male (84.05%) with a median age of 34.00 +/- 8.14 years. The median symptom duration excluding the chronic cases was 15 +/- 34.28 days. This type of leak was mostly (48.57%) seen in medium-sized CSC, and the majority were in the parafoveal superonasal quadrant (31.42%). The ascending type of leak was predominant (94.28%). In four eyes, an atypical pattern and in two eyes more than one smokestack leak were seen within the same detached area. The experimental study (Part II) demonstrated that fluid containing a low concentration of fluorescein ascended due to convection currents, whereas highly concentrated dye descended. The clinical study revealed smokestack leaks to be significantly more common in a primary acute episode, and they usually develop in the early part of the acute phase of the disease (average duration 15 +/- 34.28 days). Rarely, this type of leak can occur in the chronic stage, and multiple leaks may develop in the same detached space. The various patterns of dye movement due to convection currents in the experimental model resembled the dye movement in certain cases of CSC of the present series. The experimental study also hinted at the probability of drainage of unbound fluorescein molecules along with protein-laden heavy fluid in downward spread of the leak.

Growth, nisA Gene Expression, and In Situ Activity of Novel Lactococcus lactis subsp. cremoris Costarter Culture in Commercial Hard Cheese Production.

PubMed

Noutsopoulos, Dimitrios; Kakouri, Athanasia; Kartezini, Eleftheria; Pappas, Dimitrios; Hatziloukas, Efstathios; Samelis, John

2017-12-01

This study evaluated in situ expression of the nisA gene by an indigenous, nisin A-producing (NisA+) Lactococcus lactis subsp. cremoris raw milk genotype, represented by strain M78, in traditional Greek Graviera cheeses under real factory-scale manufacturing and ripening conditions. Cheeses were produced with added a mixed thermophilic and mesophilic commercial starter culture (CSC) or with the CSC plus strain M78 (CSC+M78). Cheeses were sampled after curd cooking (day 0), fermentation of the unsalted molds for 24 h (day 1), brining (day 7), and ripening of the brined molds (14 to 15 kg each) for 30 days in a fully controlled industrial room (16.5°C; 91% relative humidity; day 37). Total RNA was directly extracted from the cheese samples, and the expression of nisA gene was evaluated by real-time reverse transcription PCR (qRT-PCR). Agar overlay and well diffusion bioassays were correspondingly used for in situ detection of the M78 NisA+ colonies in the cheese agar plates and antilisterial activity in whole-cheese slurry samples, respectively. Agar overlay assays showed good growth (>8 log CFU/g of cheese) of the NisA+ strain M78 in coculture with the CSC and vice versa. The nisA expression was detected in CSC+M78 cheese samples only, with its expression levels being the highest (16-fold increase compared with those of the control gene) on day 1, followed by significant reduction on day 7 and almost negligible expression on day 37. Based on the results, certain intrinsic and mainly implicit hurdle factors appeared to reduce growth prevalence rates and decrease nisA gene expression, as well as the nisin A-mediated antilisterial activities of the NisA+ strain M78 postfermentation. To our knowledge, this is the first report on quantitative expression of the nisA gene in a Greek cooked hard cheese during commercial manufacturing and ripening conditions by using a novel, rarely isolated, indigenous NisA+ L. lactis subsp. cremoris genotype as costarter culture.

A Transition Zone Showing Highly Discontinuous or Alternating Levels of Stem Cell and Proliferation Markers Characterizes the Development of PTEN-Haploinsufficient Colorectal Cancer.

PubMed

Arvai, Kevin J; Hsu, Ya-Hsuan; Lee, Lobin A; Jones, Dan

2015-01-01

Stepwise acquisition of oncogene mutations and deletion/inactivation of tumor suppressor genes characterize the development of colorectal cancer (CRC). These genetic events interact with discrete morphologic transitions from hyperplastic mucosa to adenomatous areas, followed by in situ malignant transformation and finally invasive carcinoma. The goal of this study was to identify tissue markers of the adenoma-carcinoma morphogenetic transitions in CRC. We analyzed the patterns of expression of growth regulatory and stem cell markers across these distinct morphologic transition zones in 735 primary CRC tumors. In 202 cases with preserved adenoma-adenocarcinoma transition, we identified, in 37.1% of cases, a zone of adenomatous epithelium, located immediately adjacent to the invasive component, that showed rapidly alternating intraglandular stretches of PTEN+ and PTEN- epithelium. This zone exactly overlapped with similar alternating expression of Ki-67 and inversely with the transforming growth factor-beta (TGF-β) growth regulator SMAD4. These zones also show parallel alternating levels and/or subcellular localization of multiple cancer stem/progenitor cell (CSC) markers, including β-catenin/CTNNB1, ALDH1, and CD44. PTEN was always re-expressed in the invasive tumor in these cases, unlike those with complete loss of PTEN expression. Genomic microarray analysis of CRC with prominent CSC-like expansions demonstrated a high frequency of PTEN genomic deletion/haploinsufficiency in tumors with CSC-like transition zones (62.5%) but not in tumors with downregulated but non-alternating PTEN expression (14.3%). There were no significant differences in the levels of KRAS mutation or CTNNB1 mutation in CSC-like tumors as compared to unselected CRC cases. In conclusion, we have identified a distinctive CSC-like pre-invasive transition zone in PTEN-haploinsufficient CRC that shows convergent on-off regulation of the PTEN/AKT, TGF-β/SMAD and Wnt/β-catenin pathways. This bottleneck-like zone is usually followed by the emergence of invasive tumors with intact PTEN expression but dysregulated TP53 and uniformly high proliferation rates.

Culture media influenced laboratory outcomes but not neonatal birth weight in assisted reproductive technology.

PubMed

Yin, Tai-lang; Zhang, Yi; Li, Sai-jiao; Zhao, Meng; Ding, Jin-li; Xu, Wang-ming; Yang, Jing

2015-12-01

Whether the type of culture media utilized in assisted reproductive technology has impacts on laboratory outcomes and birth weight of newborns in in-vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) was investigated. A total of 673 patients undergoing IVF/ICSI and giving birth to live singletons after fresh embryo transfer on day 3 from Jan. 1, 2010 to Dec. 31, 2012 were included. Three types of culture media were used during this period: Quinn's Advantage (QA), Single Step Medium (SSM), and Continuous Single Culture medium (CSC). Fertilization rate (FR), normal fertilization rate (NFR), cleavage rate (CR), normal cleavage rate (NCR), good-quality embryo rate (GQER) and neonatal birth weight were compared using one-way ANOVA and χ (2) tests. Multiple linear regression analysis was performed to determine the impact of culture media on laboratory outcomes and birth weight. In IVF cycles, GQER was significantly decreased in SSM medium group as compared with QA or CSC media groups (63.6% vs. 69.0% in QA; vs. 71.3% in CSC, P=0.011). In ICSI cycles, FR, NFR and CR were significantly lower in CSC medium group than in other two media groups. No significant difference was observed in neonatal birthweight among the three groups (P=0.759). Multiple linear regression analyses confirmed that the type of culture medium was correlated with FR, NFR, CR and GQER, but not with neonatal birth weight. The type of culture media had potential influences on laboratory outcomes but did not exhibit an impact on the birth weight of singletons in ART.

Cancer stem cells (CSCs), cervical CSCs and targeted therapies

PubMed Central

Huang, Ruixia; Rofstad, Einar K.

2017-01-01

Accumulating evidence has shown that cancer stem cells (CSCs) have a tumour-initiating capacity and play crucial roles in tumour metastasis, relapse and chemo/radio-resistance. As tumour propagation initiators, CSCs are considered to be promising targets for obtaining a better therapeutic outcome. Cervical carcinoma is the most common gynaecological malignancy and has a high cancer mortality rate among females. As a result, the investigation of cervical cancer stem cells (CCSCs) is of great value. However, the numbers of cancer cells and corresponding CSCs in malignancy are dynamically balanced, and CSCs may reside in the CSC niche, about which little is known to date. Therefore, due to their complicated molecular phenotypes and biological behaviours, it remains challenging to obtain “purified” CSCs and continuously culture CSCs for further in vitro studies without the cells losing their stem properties. At present, CSC-related markers and functional assays are used to purify, identify and therapeutically target CSCs both in vitro and in vivo. Nevertheless, CSC-related markers are not universal to all tumour types, although some markers may be valid in multiple tumour types. Additionally, functional identifications based on CSC-specific properties are usually limited in in vivo studies. Furthermore, an optimal method for identifying potential CCSCs in CCSC studies has not been previously published, and these techniques are currently of great importance. This article updates our knowledge on CSCs and CCSCs, reviews potential stem cell markers and functional assays for identifying CCSCs, and describes the potential of targeting CCSCs in the treatment of cervical carcinoma. PMID:27343550

Inhibition of organic anion transporter (OAT) activity by cigarette smoke condensate.

PubMed

Sayyed, Katia; Le Vee, Marc; Abdel-Razzak, Ziad; Fardel, Olivier

2017-10-01

Cigarette smoke condensate (CSC) has previously been shown to impair activity and expression of hepatic drug transporters. In the present study, we provided evidence that CSC also hinders activity of organic anion transporters (OATs), notably expressed at the kidney level. CSC thus cis-inhibited OAT substrate uptake in OAT1- and OAT3-transfected HEK293 cells, in a concentration-dependent manner (IC 50 =72.1μg/mL for OAT1 inhibition and IC 50 =27.3μg/mL for OAT3 inhibition). By contrast, OAT4 as well as the renal organic cation transporter (OCT) 2 were less sensitive to the inhibitory effect of CSC (IC 50 =351.5μg/mL and IC 50 =226.2μg/mL, for inhibition of OAT4 and OCT2, respectively). OAT3 activity was further demonstrated to be blocked by some single chemicals present in cigarette smoke such as the heterocyclic amines AαC (IC 50 =11.3μM) and PhIP (IC 50 =1.9μM), whereas other major cigarette smoke components used at 100μM, like nicotine, the nitrosamine NNK and the polycyclic aromatic hydrocarbons benzo(a)pyrene and phenanthrene, were without effect. AαC and PhIP however failed to trans-stimulate activity of OAT3, suggesting that they were not substrates for this transporter. Taken together, these data establish OAT1 and OAT3 transporters as targets of cigarette smoke chemicals, which may contribute to smoking-associated pharmacokinetics alterations. Copyright © 2017 Elsevier Ltd. All rights reserved.

The Chandra Source Catalog 2.0: Data Processing Pipelines

NASA Astrophysics Data System (ADS)

Miller, Joseph; Allen, Christopher E.; Budynkiewicz, Jamie A.; Gibbs, Danny G., II; Paxson, Charles; Chen, Judy C.; Anderson, Craig S.; Burke, Douglas; Civano, Francesca Maria; D'Abrusco, Raffaele; Doe, Stephen M.; Evans, Ian N.; Evans, Janet D.; Fabbiano, Giuseppina; Glotfelty, Kenny J.; Graessle, Dale E.; Grier, John D.; Hain, Roger; Hall, Diane M.; Harbo, Peter N.; Houck, John C.; Lauer, Jennifer L.; Laurino, Omar; Lee, Nicholas P.; Martínez-Galarza, Juan Rafael; McCollough, Michael L.; McDowell, Jonathan C.; McLaughlin, Warren; Morgan, Douglas L.; Mossman, Amy E.; Nguyen, Dan T.; Nichols, Joy S.; Nowak, Michael A.; Plummer, David A.; Primini, Francis Anthony; Rots, Arnold H.; Siemiginowska, Aneta; Sundheim, Beth A.; Tibbetts, Michael; Van Stone, David W.; Zografou, Panagoula

2018-01-01

With the construction of the Second Chandra Source Catalog (CSC2.0), came new requirements and new techniques to create a software system that can process 10,000 observations and identify nearly 320,000 point and compact X-ray sources. A new series of processing pipelines have been developed to allow for deeper more complete exploration of the Chanda observations. In CSC1.0 there were 4 general pipelines, whereas in CSC2.0 there are 20 data processing pipelines that have been organized into 3 distinct phases of operation - detection, master matching and source property characterization.With CSC2.0, observations within one arcminute of each other are stacked before searching for sources. The detection phase of processing combines the data, adjusts for shifts in fine astrometry, detects sources, and assesses the likelihood that sources are real. During the master source phase, detections across stacks of observations are analyzed for coverage of the same source to produce a master source. Finally, in the source property phase, each source is characterized with aperture photometry, spectrometry, variability and other properties at theobservation, stack and master levels over several energy bands.We present how these pipelines were constructed and the challenges we faced in how we processed data ranging from virtually no counts to millions of counts, how pipelines were tuned to work optimally on a computational cluster, and how we ensure the data produced was correct through various quality assurance steps.This work has been supported by NASA under contract NAS 8-03060 to the Smithsonian Astrophysical Observatory for operation of the Chandra X-ray Center.

Optimization modeling to maximize population access to comprehensive stroke centers

PubMed Central

Branas, Charles C.; Kasner, Scott E.; Wolff, Catherine; Williams, Justin C.; Albright, Karen C.; Carr, Brendan G.

2015-01-01

Objective: The location of comprehensive stroke centers (CSCs) is critical to ensuring rapid access to acute stroke therapies; we conducted a population-level virtual trial simulating change in access to CSCs using optimization modeling to selectively convert primary stroke centers (PSCs) to CSCs. Methods: Up to 20 certified PSCs per state were selected for conversion to maximize the population with 60-minute CSC access by ground and air. Access was compared across states based on region and the presence of state-level emergency medical service policies preferentially routing patients to stroke centers. Results: In 2010, there were 811 Joint Commission PSCs and 0 CSCs in the United States. Of the US population, 65.8% had 60-minute ground access to PSCs. After adding up to 20 optimally located CSCs per state, 63.1% of the US population had 60-minute ground access and 86.0% had 60-minute ground/air access to a CSC. Across states, median CSC access was 55.7% by ground (interquartile range 35.7%–71.5%) and 85.3% by ground/air (interquartile range 59.8%–92.1%). Ground access was lower in Stroke Belt states compared with non–Stroke Belt states (32.0% vs 58.6%, p = 0.02) and lower in states without emergency medical service routing policies (52.7% vs 68.3%, p = 0.04). Conclusion: Optimal system simulation can be used to develop efficient care systems that maximize accessibility. Under optimal conditions, a large proportion of the US population will be unable to access a CSC within 60 minutes. PMID:25740858

Treatment of ovarian cancer by targeting the tumor stem cell-associated carbohydrate antigen, Sialyl-Thomsen-nouveau

PubMed Central

Starbuck, Kristen; Al-Alem, Linah; Eavarone, David A.; Hernandez, Silvia Fatima; Bellio, Chiara; Prendergast, Jillian M.; Stein, Jenna; Dransfield, Daniel T.; Zarrella, Bianca; Growdon, Whitfield B.; Behrens, Jeff; Foster, Rosemary; Rueda, Bo R.

2018-01-01

Recurrent ovarian cancer (OvCa) is thought to result in part from the inability to eliminate rare quiescent cancer stem cells (CSCs) that survive cytotoxic chemotherapy and drive tumor resurgence. The Sialyl-Thomsen-nouveau antigen (STn) is a carbohydrate moiety present on protein markers of CSCs in pancreatic, colon, and gastric malignancies. We have demonstrated that human OvCa cell lines contain varying levels of cells that independently express either STn or the ovarian CSC marker CD133. Here we determine co-expression of STn and CD133 in a subset of human OvCa cell lines. Analyses of colony and sphere forming capacity and of response to standard-of-care cytotoxic therapy suggest a subset of OvCa STn+ cells display some CSC features. The effect of the anti-STn antibody-drug conjugates (ADCs) S3F-CL-MMAE and 2G12-2B2-CL-MMAE on OvCa cell viability in vitro and in vivo was also assessed. Treatment with S3F-CL-MMAE reduced the viability of two of three OvCa cell lines in vitro and exposure to either S3F-CL-MMAE or 2G12-2B2-CL-MMAE reduced OVCAR3-derived xenograft volume in vivo, depleting STn+ tumor cells. In summary, STn+ cells demonstrate some stem-like properties and specific therapeutic targeting of STn in ovarian tumors may be an effective clinical strategy to eliminate both STn+ CSC and STn+ non-CSC populations. PMID:29796189

Analysis of tumoral spheres growing in a multichamber microfluidic device.

PubMed

Belgorosky, Denise; Fernández-Cabada, Tamara; Peñaherrera-Pazmiño, Ana Belén; Langle, Yanina; Booth, Ross; Bhansali, Shekhar; Pérez, Maximiliano S; Eiján, Ana María; Lerner, Betiana

2018-09-01

Lab on a Chip (LOC) farming systems have emerged as a powerful tool for single cell studies combined with a non-adherent cell culture substrate and single cell capture chips for the study of single cell derived tumor spheres. Cancer is characterized by its cellular heterogeneity where only a small population of cancer stem cells (CSCs) are responsible for tumor metastases and recurrences. Thus, the in vitro strategy to the formation of a single cell-derived sphere is an attractive alternative to identify CSCs. In this study, we test the effectiveness of microdevices for analysis of heterogeneity within CSC populations and its interaction with different components of the extracellular matrix. CSC could be identify using specific markers related to its pluripotency and self-renewal characteristics such as the transcription factor Oct-4 or the surface protein CD44. The results confirm the usefulness of LOC as an effective method for quantification of CSC, through the formation of spheres under conditions of low adhesion or growing on components of the extracellular matrix. The device used is also a good alternative for evaluating the individual growth of each sphere and further identification of these CSC markers by immunofluorescence. In conclusion, LOC devices have not only the already known advantages, but they are also a promising tool since they use small amounts of reagents and are under specific culture parameters. LOC devices could be considered as a novel technology to be used as a complement or replacement of traditional studies on culture plates. © 2018 Wiley Periodicals, Inc.

Chronic psychosocial stress causes delayed extinction and exacerbates reinstatement of ethanol-induced conditioned place preference in mice.

PubMed

Bahi, Amine; Dreyer, Jean-Luc

2014-01-01

We have shown previously, using an animal model of voluntary ethanol intake and ethanol-conditioned place preference (EtOH-CPP), that exposure to chronic psychosocial stress induces increased ethanol intake and EtOH-CPP acquisition in mice. Here, we examined the impact of chronic subordinate colony (CSC) exposure on EtOH-CPP extinction, as well as ethanol-induced reinstatement of CPP. Mice were conditioned with saline or 1.5 g/kg ethanol and were tested in the EtOH-CPP model. In the first experiment, the mice were subjected to 19 days of chronic stress, and EtOH-CPP extinction was assessed during seven daily trials without ethanol injection. In the second experiment and after the EtOH-CPP test, the mice were subjected to 7 days of extinction trials before the 19 days of chronic stress. Drug-induced EtOH-CPP reinstatement was induced by a priming injection of 0.5 g/kg ethanol. Compared to the single-housed colony mice, CSC mice exhibited increased anxiety-like behavior in the elevated plus maze (EPM) and the open field tests. Interestingly, the CSC mice showed delayed EtOH-CPP extinction. More importantly, CSC mice showed increased alcohol-induced reinstatement of the EtOH-CPP behavior. Taken together, this study indicates that chronic psychosocial stress can have long-term effects on EtOH-CPP extinction as well as drug-induced reinstatement behavior and may provide a suitable model to study the latent effects of chronic psychosocial stress on extinction and relapse to drug abuse.

Optimization modeling to maximize population access to comprehensive stroke centers.

PubMed

Mullen, Michael T; Branas, Charles C; Kasner, Scott E; Wolff, Catherine; Williams, Justin C; Albright, Karen C; Carr, Brendan G

2015-03-24

The location of comprehensive stroke centers (CSCs) is critical to ensuring rapid access to acute stroke therapies; we conducted a population-level virtual trial simulating change in access to CSCs using optimization modeling to selectively convert primary stroke centers (PSCs) to CSCs. Up to 20 certified PSCs per state were selected for conversion to maximize the population with 60-minute CSC access by ground and air. Access was compared across states based on region and the presence of state-level emergency medical service policies preferentially routing patients to stroke centers. In 2010, there were 811 Joint Commission PSCs and 0 CSCs in the United States. Of the US population, 65.8% had 60-minute ground access to PSCs. After adding up to 20 optimally located CSCs per state, 63.1% of the US population had 60-minute ground access and 86.0% had 60-minute ground/air access to a CSC. Across states, median CSC access was 55.7% by ground (interquartile range 35.7%-71.5%) and 85.3% by ground/air (interquartile range 59.8%-92.1%). Ground access was lower in Stroke Belt states compared with non-Stroke Belt states (32.0% vs 58.6%, p = 0.02) and lower in states without emergency medical service routing policies (52.7% vs 68.3%, p = 0.04). Optimal system simulation can be used to develop efficient care systems that maximize accessibility. Under optimal conditions, a large proportion of the US population will be unable to access a CSC within 60 minutes. © 2015 American Academy of Neurology.

Branched Chain Amino Acid Suppresses Hepatocellular Cancer Stem Cells through the Activation of Mammalian Target of Rapamycin

PubMed Central

Nishitani, Shinobu; Horie, Mayumi; Ishizaki, Sonoko; Yano, Hirohisa

2013-01-01

Differentiation of cancer stem cells (CSCs) into cancer cells causes increased sensitivity to chemotherapeutic agents. Although inhibition of mammalian target of rapamycin (mTOR) leads to CSC survival, the effect of branched chain amino acids (BCAAs), an mTOR complex 1 (mTORC1) activator remains unknown. In this study, we examined the effects of BCAA on hepatocellular carcinoma (HCC) cells expressing a hepatic CSC marker, EpCAM. We examined the effects of BCAA and/or 5-fluorouracil (FU) on expression of EpCAM and other CSC-related markers, as well as cell proliferation in HCC cells and in a xenograft mouse model. We also characterized CSC-related and mTOR signal-related molecule expression and tumorigenicity in HCC cells with knockdown of Rictor or Raptor, or overexpression of constitutively active rheb (caRheb). mTOR signal-related molecule expression was also examined in BCAA-treated HCC cells. In-vitro BCAA reduced the frequency of EpCAM-positive cells and improved sensitivity to the anti-proliferative effect of 5-FU. Combined 5-FU and BCAA provided better antitumor efficacy than 5-FU alone in the xenograft model. Stimulation with high doses of BCAA activated mTORC1. Knockdown and overexpression experiments revealed that inhibition of mTOR complex 2 (mTORC2) or activation of mTORC1 led to decreased EpCAM expression and little or no tumorigenicity. BCAA may enhance the sensitivity to chemotherapy by reducing the population of cscs via the mTOR pathway. This result suggests the utility of BCAA in liver cancer therapy. PMID:24312415

Wilms Tumor NCAM-Expressing Cancer Stem Cells as Potential Therapeutic Target for Polymeric Nanomedicine.

PubMed

Markovsky, Ela; Vax, Einav; Ben-Shushan, Dikla; Eldar-Boock, Anat; Shukrun, Rachel; Yeini, Eilam; Barshack, Iris; Caspi, Revital; Harari-Steinberg, Orit; Pode-Shakked, Naomi; Dekel, Benjamin; Satchi-Fainaro, Ronit

2017-11-01

Cancer stem cells (CSC) form a specific population within the tumor that has been shown to have self-renewal and differentiation properties, increased ability to migrate and form metastases, and increased resistance to chemotherapy. Consequently, even a small number of cells remaining after therapy can repopulate the tumor and cause recurrence of the disease. CSCs in Wilms tumor, a pediatric renal cancer, were previously shown to be characterized by neural cell adhesion molecule (NCAM) expression. Therefore, NCAM provides a specific biomarker through which the CSC population in this tumor can be targeted. We have recently developed an NCAM-targeted nanosized conjugate of paclitaxel bound to a biodegradable polyglutamic acid polymer. In this work, we examined the ability of the conjugate to inhibit Wilms tumor by targeting the NCAM-expressing CSCs. Results show that the conjugate selectively depleted the CSC population of the tumors and effectively inhibited tumor growth without causing toxicity. We propose that the NCAM-targeted conjugate could be an effective therapeutic for Wilms tumor. Mol Cancer Ther; 16(11); 2462-72. ©2017 AACR . ©2017 American Association for Cancer Research.

ECM1 regulates tumor metastasis and CSC-like property through stabilization of β-catenin.

PubMed

Lee, K-m; Nam, K; Oh, S; Lim, J; Kim, R K; Shim, D; Choi, J-h; Lee, S-J; Yu, J-H; Lee, J W; Ahn, S H; Shin, I

2015-12-10

Extracellular Matrix Protein 1 (ECM1) is a marker for tumorigenesis and is correlated with invasiveness and poor prognosis in various types of cancer. However, the functional role of ECM1 in cancer metastasis is unclear. Here, we detected high ECM1 level in breast cancer patient sera that was associated with recurrence of tumor. The modulation of ECM1 expression affected not only cell migration and invasion, but also sphere-forming ability and drug resistance in breast cancer cell lines. In addition, ECM1 regulated the gene expression associated with the epithelial to mesenchymal transition (EMT) progression and cancer stem cell (CSC) maintenance. Interestingly, ECM1 increased β-catenin expression at the post-translational level through induction of MUC1, which was physically associated with β-catenin. Indeed, the association between β-catenin and the MUC1 cytoplasmic tail was increased by ECM1. Furthermore, forced expression of β-catenin altered the gene expression that potentiated EMT progression and CSC phenotype maintenance in the cells. These data provide evidence that ECM1 has an important role in cancer metastasis through β-catenin stabilization.

Repositioning chloroquine and metformin to eliminate cancer stem cell traits in pre-malignant lesions.

PubMed

Vazquez-Martin, Alejandro; López-Bonetc, Eugeni; Cufí, Sílvia; Oliveras-Ferraros, Cristina; Del Barco, Sonia; Martin-Castillo, Begoña; Menendez, Javier A

2011-01-01

Ideal oncology drugs would be curative after a short treatment course if they could eliminate epithelium-originated carcinomas at their non-invasive, pre-malignant stages. Such ideal molecules, which are expected to molecularly abrogate all the instrumental mechanisms acquired by migrating cancer stem cells (CSCs) to by-pass tumour suppressor barriers, might already exist. We here illustrate how system biology strategies for repositioning existing FDA-approved drugs may accelerate our therapeutic capacity to eliminate CSC traits in pre-invasive intraepithelial neoplasias. First, we describe a signalling network signature that overrides bioenergetics stress- and oncogene-induced senescence (OIS) phenomena in CSCs residing at pre-invasive lesions. Second, we functionally map the anti-malarial chloroquine and the anti-diabetic metformin ("old drugs") to their recently recognized CSC targets ("new uses") within the network. By discussing the preclinical efficacy of chloroquine and metformin to inhibiting the genesis and self-renewal of CSCs we finally underscore the expected translational impact of the "old drugs-new uses" repurposing strategy to open a new CSC-targeted chemoprevention era. Copyright © 2011 Elsevier Ltd. All rights reserved.

Repositioning chloroquine and metformin to eliminate cancer stem cell traits in pre-malignant lesions

PubMed Central

Vazquez-Martin, Alejandro; López-Bonetc, Eugeni; Cufí, Sílvia; Oliveras-Ferraros, Cristina; Del Barco, Sonia; Martin-Castillo, Begoña; Menendez, Javier A.

2013-01-01

Ideal oncology drugs would be curative after a short treatment course if they could eliminate epithelium-originated carcinomas at their non-invasive, pre-malignant stages. Such ideal molecules, which are expected to molecularly abrogate all the instrumental mechanisms acquired by migrating cancer stem cells (CSCs) to by-pass tumour suppressor barriers, might already exist. We here illustrate how system biology strategies for repositioning existing FDA-approved drugs may accelerate our therapeutic capacity to eliminate CSC traits in pre-invasive intraepithelial neoplasias. First, we describe a signalling network signature that overrides bioenergetics stress- and oncogene-induced senescence (OIS) phenomena in CSCs residing at pre-invasive lesions. Second, we functionally map the anti-malarial chloroquine and the anti-diabetic metformin (“old drugs”) to their recently recognized CSC targets (“new uses”) within the network. By discussing the preclinical efficacy of chloroquine and metformin to inhibiting the genesis and self-renewal of CSCs we finally underscore the expected translational impact of the “old drugs–new uses” repurposing strategy to open a new CSC-targeted chemoprevention era. PMID:21600837

Engineering cocrystal solubility, stability, and pH(max) by micellar solubilization.

PubMed

Huang, Neal; Rodríguez-Hornedo, Naír

2011-12-01

Cocrystals offer great promise in enhancing drug aqueous solubilities, but face the challenge of conversion to a less soluble drug when in contact with solvent. This manuscript shows that differential solubilization of cocrystal components by micelles can impart thermodynamic stability to otherwise unstable cocrystals. The theoretical foundation for controlling cocrystal solubility and stability is presented by considering the contributions of micellar solubilization and ionization of cocrystal components. A surfactant critical stabilization concentration (CSC) and a solution pH (pH(max)) where cocrystal and drug are thermodynamically stable are shown to characterize cocrystal stability in micellar solutions. The solubility, CSC, and pH(max) of carbamazepine cocrystals in micellar solutions of sodium lauryl sulfate predicted by the models are in very good agreement with experimental measurements. The findings from this work demonstrate that cocrystal CSC and pH(max) can be tailored from the selection of coformer and solubilizing additives such as surfactants, thus providing an unprecedented level of control over cocrystal stability and solubility via solution phase chemistry. Copyright © 2011 Wiley-Liss, Inc.

Communications among elements of a space construction ensemble

NASA Technical Reports Server (NTRS)

Davis, Randal L.; Grasso, Christopher A.

1989-01-01

Space construction projects will require careful coordination between managers, designers, manufacturers, operators, astronauts, and robots with large volumes of information of varying resolution, timeliness, and accuracy flowing between the distributed participants over computer communications networks. Within the CSC Operations Branch, we are researching the requirements and options for such communications. Based on our work to date, we feel that communications standards being developed by the International Standards Organization, the CCITT, and other groups can be applied to space construction. We are currently studying in depth how such standards can be used to communicate with robots and automated construction equipment used in a space project. Specifically, we are looking at how the Manufacturing Automation Protocol (MAP) and the Manufacturing Message Specification (MMS), which tie together computers and machines in automated factories, might be applied to space construction projects. Together with our CSC industrial partner Computer Technology Associates, we are developing a MAP/MMS companion standard for space construction and we will produce software to allow the MAP/MMS protocol to be used in our CSC operations testbed.

Department of the Interior Climate Science Centers

USGS Publications Warehouse

Jones, Sonya A.

2011-01-01

What is a Climate Science Center? On September 14, 2009, the Secretary of the Interior signed a Secretarial Order (No. 3289) entitled, "Addressing the Impacts of Climate Change on America's Water, Land, and Other Natural and Cultural Resources." The Order effectively established the U.S. Department of the Interior (DOI) Climate Science Centers (CSCs), which will integrate DOI science and management expertise with similar contributions from our partners to provide information to support adaptation and mitigation efforts on both public and private lands, across the United States and internationally.The Southeast CSC, hosted by NC State University (NCSU), will collaborate with a number of other universities, State and Federal agencies, and nongovernmental organizations (NGOs) with interest and expertise in climate science. The primary partner for the Southeast CSC will be the Landscape Conservation Cooperatives (LCCs) in the Southeast, including the Appalachian, Gulf Coastal Plains and Ozarks, Gulf Coast Prairie, Peninsular Florida, and the South Atlantic. CSC collaborations are focused on common science priorities, addressing priority partner needs, minimizing redundancies in science, sharing scientific findings, and expanding understanding of climate change impacts in the Southeast.

Proteogenomic analysis of NCC-S1M, a gastric cancer stem cell-like cell line that responds to anti-PD-1.

PubMed

Park, Jun Won; Um, Hyejin; Yang, Hanna; Ko, Woori; Kim, Dae-Yong; Kim, Hark Kyun

2017-03-11

To elucidate signaling pathways that regulate gastric cancer stem cell (CSC) phenotypes and immune checkpoint, we performed a proteogenomic analysis of NCC-S1M, which is a gastric cancer cell line with CSC-like characteristics and is the only syngeneic gastric tumor cell line transplant model created in the scientific community. We found that the NCC-S1M allograft was responsive to anti-PD-1 treatment, and overexpressed Cd274 encoding PD-L1. PD-L1 was transcriptionally activated by loss of the TGF-β signaling. Il1rl1 protein was overexpressed in NCC-S1M cells compared with NCC-S1 cells that are less tumorigenic and less chemoresistant. Il1rl1 knockdown in NCC-S1M cells reduced tumorigenic potential and in vivo chemoresistance. Our proteogenomic analysis demonstrates a role of Smad4 loss in the PD-L1 immune evasion, as well as Il1rl1's role in CSC-like properties of NCC-S1M. Copyright © 2017 Elsevier Inc. All rights reserved.

The Aquarius Simulator and Cold-Sky Calibration

NASA Technical Reports Server (NTRS)

Le Vine, David M.; Dinnat, Emmanuel P.; Abraham, Saji; deMatthaeis, Paolo; Wentz, Frank J.

2011-01-01

A numerical simulator has been developed to study remote sensing from space in the spectral window at 1.413 GHz (L-band), and it has been used to optimize the cold-sky calibration (CSC) for the Aquarius radiometers. The celestial sky is a common cold reference in microwave radiometry. It is currently being used by the Soil Moisture and Ocean Salinity satellite, and it is planned that, after launch, the Aquarius/SAC-D observatory will periodically rotate to view "cold sky" as part of the calibration plan. Although radiation from the celestial sky is stable and relatively well known, it varies with location. In addition, radiation from the Earth below contributes to the measured signal through the antenna back lobes and also varies along the orbit. Both effects must be taken into account for a careful calibration. The numerical simulator has been used with the Aquarius configuration (antennas and orbit) to investigate these issues and determine optimum conditions for performing a CSC. This paper provides an overview of the simulator and the analysis leading to the selection of the optimum locations for a CSC.

DNMT1 is essential for mammary and cancer stem cell maintenance and tumorigenesis

PubMed Central

Pathania, Rajneesh; Ramachandran, Sabarish; Elangovan, Selvakumar; Padia, Ravi; Yang, Pengyi; Cinghu, Senthilkumar; Veeranan-Karmegam, Rajalakshmi; Arjunan, Pachiappan; Gnana-Prakasam, Jaya P.; Fulzele, Sadanand; Pei, Lirong; Chang, Chang-Sheng; Choi, Hyeon; Shi, Huidong; Manicassamy, Santhakumar; Prasad, Puttur D.; Sharma, Suash; Ganapathy, Vadivel; Jothi, Raja; Thangaraju, Muthusamy

2015-01-01

Mammary stem/progenitor cells (MaSCs) maintain self-renewal of the mammary epithelium during puberty and pregnancy. DNA methylation provides a potential epigenetic mechanism for maintaining cellular memory during self-renewal. Although DNA methyltransferases (DNMTs) are dispensable for embryonic stem cell maintenance, their role in maintaining MaSCs and cancer stem cells (CSCs) in constantly replenishing mammary epithelium is unclear. Here we show that DNMT1 is indispensable for MaSC maintenance. Furthermore, we find that DNMT1 expression is elevated in mammary tumors, and mammary gland-specific DNMT1 deletion protects mice from mammary tumorigenesis by limiting the CSC pool. Through genome-scale methylation studies, we identify ISL1 as a direct DNMT1 target, hypermethylated and downregulated in mammary tumors and CSCs. DNMT inhibition or ISL1 expression in breast cancer cells limits CSC population. Altogether, our studies uncover an essential role for DNMT1 in MaSC and CSC maintenance and identify DNMT1-ISL1 axis as a potential therapeutic target for breast cancer treatment. PMID:25908435

Cancer stem cells in the development of liver cancer

PubMed Central

Yamashita, Taro; Wang, Xin Wei

2013-01-01

Liver cancer is an aggressive disease with a poor outcome. Several hepatic stem/progenitor markers are useful for isolating a subset of liver cells with stem cell features, known as cancer stem cells (CSCs). These cells are responsible for tumor relapse, metastasis, and chemoresistance. Liver CSCs dictate a hierarchical organization that is shared in both organogenesis and tumorigenesis. An increased understanding of the molecular signaling events that regulate cellular hierarchy and stemness, and success in defining key CSC-specific genes, have opened up new avenues to accelerate the development of novel diagnostic and treatment strategies. This Review highlights recent advances in understanding the pathogenesis of liver CSCs and discusses unanswered questions about the concept of liver CSCs. PMID:23635789

NRC/AMRMC Resident Research Associateship Program

DTIC Science & Technology

2013-03-01

Luciana 5/18/2011-8/17/2012 1 Intravital Microscopy was successfully employed for investigating EG shedding in hemorrhagic shock/resuscitation for...05/2013 3/18/2013, 3:21 PM 2 Intravital microscopy integrated with systemic hemodynamics evaluations may be essential and more accurate tools to...concise form, utilizing key concepts/words. 1) Intravital Microscopy was successfully employed for investigating EG shedding in hemorrhagic

Imagine, Invent, Program, Share: A Library-Hosted Computer Club Promotes 21st Century Skills

ERIC Educational Resources Information Center

Myers, Brian

2009-01-01

During at least one afternoon each month, Wilmette (Illinois) Public Library (WPL) hosts a local group of computer programmers, designers, and artists, who meet to discuss digital projects and resources, technical challenges, and successful design or programming strategies. WPL's Game Design Club, now in its third year, owes its existence to a…

A Phenomenological Study Examining the Experiences of High School Graduates Who Participated in a Career and Technical Education Program of Study

ERIC Educational Resources Information Center

Goins, Camille Locklear

2015-01-01

Career and Technical Education (CTE) programs are designed to help prepare students to become effective workers by equipping them with college and career readiness skills needed for the 21st century workplace. Students who participate in a CTE Program of Study (POS) have the potential for greater success during and after high school because they…

Successful strategies for building thriving undergraduate physics programs at minority serving institutions

NASA Astrophysics Data System (ADS)

Williams, Quinton

2013-03-01

After having been pulled back from the brink of academic program deletion, Jackson State University (Jackson, Mississippi) is now the only HBCU (Historically Black College and University) listed as a top producer of B.S. degrees earned by African Americans in both fields of physics and geoscience. Very pragmatic, strategic actions were taken to enhance the undergraduate degree program which resulted in it becoming one of the most productive academic units at the university. Successful strategies will be shared for growing the enrollment of physics majors, building productive research/educational programs, and improving the academic performance of underprepared students. Despite myriad challenges faced by programs at minority serving institutions in a highly competitive 21st century higher education system, it is still possible for undergraduate physics programs to transition from surviving to thriving.

Bruton's tyrosine kinase (Btk) inhibitor ibrutinib suppresses stem-like traits in ovarian cancer

PubMed Central

Zucha, Muhammad Ary; Wu, Alexander T.H.; Lee, Wei-Hwa; Wang, Liang-Shun; Lin, Wan-Wan; Yuan, Chiou-Chung; Yeh, Chi-Tai

2015-01-01

According to a Prognoscan database, upregulation of Bruton's tyrosine kinase (Btk) is associated with low overall survival in ovarian cancer patients. We found that spheroids-forming ovarian cancer cell, which highly expressed cancer stem-like cell (CSC) markers and Btk, were cisplatin resistant. We next treated CSCs and non-CSCs by a combination of ibrutinib and cisplatin. We found that chemoresistance was dependent on Btk and JAK2/STAT3, which maintained CSC by inducing Sox-2 and prosurvival genes. We suggest that addition of ibrutinib to cisplatin may improve treatment outcome in ovarian cancer. PMID:26036311

Bruton's tyrosine kinase (Btk) inhibitor ibrutinib suppresses stem-like traits in ovarian cancer.

PubMed

Zucha, Muhammad Ary; Wu, Alexander T H; Lee, Wei-Hwa; Wang, Liang-Shun; Lin, Wan-Wan; Yuan, Chiou-Chung; Yeh, Chi-Tai

2015-05-30

According to a Prognoscan database, upregulation of Bruton's tyrosine kinase (Btk) is associated with low overall survival in ovarian cancer patients. We found that spheroids-forming ovarian cancer cell, which highly expressed cancer stem-like cell (CSC) markers and Btk, were cisplatin resistant. We next treated CSCs and non-CSCs by a combination of ibrutinib and cisplatin. We found that chemoresistance was dependent on Btk and JAK2/STAT3, which maintained CSC by inducing Sox-2 and prosurvival genes. We suggest that addition of ibrutinib to cisplatin may improve treatment outcome in ovarian cancer.

Knowledge and Understanding of 21st Century Skills through Educator Externships: Programs in Southern New England

ERIC Educational Resources Information Center

Gibson-Cayouette, Lizann R.

2010-01-01

An acute shortage of a competent, highly-skilled workforce faces the United States workplace. Studies and reports from 1983 to present, repeatedly state that the education system in the United States must change to prepare the emergent workforce for success in the 21st century global challenges of both post-secondary education and the workplace.…

miRNA-regulated delivery of lincRNA-p21 suppresses β-catenin signaling and tumorigenicity of colorectal cancer stem cells.

PubMed

Wang, Jun; Lei, Zeng-jie; Guo, Yan; Wang, Tao; Qin, Zhong-yi; Xiao, Hua-liang; Fan, Li-lin; Chen, Dong-feng; Bian, Xiu-wu; Liu, Jia; Wang, Bin

2015-11-10

Cancer stem cells (CSCs) are key cellular targets for effective cancer therapy, due to their critical roles in cancer progression and chemo/radio-resistance. Emerging evidence demonstrates that long non-coding RNAs (lncRNAs) are important players in the biology of cancers. However, it remains unknown whether lncRNAs could be exploited to target CSCs. We report that large intergenic non-coding RNA p21 (lincRNA-p21) is a potent suppressor of stem-like traits of CSCs purified from both primary colorectal cancer (CRC) tissues and cell lines. A novel lincRNA-p21-expressing adenoviral vector, which was armed with miRNA responsive element (MRE) of miR-451 (Ad-lnc-p21-MRE), was generated to eliminate CRC CSCs. Integration of miR-451 MREs into the adenovirus efficiently delivered lincRNA-p21 into CSCs that contained low levels of miR-451. Moreover, lincRNA-p21 inhibited the activity of β-catenin signaling, thereby attenuating the viability, self-renewal, and glycolysis of CSCs in vitro. By limiting dilution and serial tumor formation assay, we demonstrated that Ad-lnc-p21-MRE significantly suppressed the self-renewal potential and tumorigenicity of CSCs in nude mice. Importantly, application of miR-451 MREs appeared to protect normal liver cells from off-target expression of lincRNA-p21 in both tumor-bearing and naïve mice. Taken together, these findings suggest that lncRNAs may be promising therapeutic molecules to eradicate CSCs and MREs of tumor-suppressor miRNAs, such as miR-451, may be exploited to ensure the specificity of CSC-targeting strategies.

The Importance of Information Requirements in Designing Acquisition to Information Systems

NASA Technical Reports Server (NTRS)

Davis, Bruce A.; Hill, Chuck; Maughan, Paul M.

1998-01-01

The partnership model used by NASA's Commercial Remote Sensing Program has been successful in better defining remote sensing functional requirements and translation to technical specifications to address environmental needs of the 21st century.

Preparing Postbaccalaureates for Entry and Success in Biomedical PhD Programs

PubMed Central

Hall, Joshua D.; Harrell, Jessica R.; Cohen, Kimberley W.; Miller, Virginia L.; Phelps, Patricia V.; Cook, Jeanette G.

2016-01-01

Certain racial and ethnic groups, individuals with disabilities, and those from low socioeconomic backgrounds remain underrepresented (UR) in the biomedical sciences. This underrepresentation becomes more extreme at each higher education stage. To support UR scholars during the critical transition from baccalaureate to PhD, we established an intensive, 1-yr postbaccalaureate training program. We hypothesized that this intervention would strengthen each participant’s competitiveness for leading PhD programs and build a foundation of skills and self-efficacy important for success during and after graduate school. Scholar critical analysis skills, lab technique knowledge, and Graduate Record Examination scores all improved significantly during the program. Scholars reported significant confidence growth in 21 of 24 categories related to success in research careers. In 5 yr, 91% (41/45) of scholars transitioned directly into PhD programs. Importantly, 40% (18/45) of participating postbaccalaureate scholars had previously been declined acceptance into graduate school; however, 17/18 of these scholars directly entered competitive PhD programs following our training program. Alumni reported they were “extremely well” prepared for graduate school, and 95% (39/41) are currently making progress to graduation with a PhD. In conclusion, we report a model for postbaccalaureate training that could be replicated to increase participation and success among UR scholars in the biomedical sciences. PMID:27496358

The Chandra Source Catalog

NASA Astrophysics Data System (ADS)

Evans, Ian; Primini, Francis A.; Glotfelty, Kenny J.; Anderson, Craig S.; Bonaventura, Nina R.; Chen, Judy C.; Davis, John E.; Doe, Stephen M.; Evans, Janet D.; Fabbiano, Giuseppina; Galle, Elizabeth C.; Gibbs, Danny G., II; Grier, John D.; Hain, Roger; Hall, Diane M.; Harbo, Peter N.; He, Xiang Qun (Helen); Houck, John C.; Karovska, Margarita; Kashyap, Vinay L.; Lauer, Jennifer; McCollough, Michael L.; McDowell, Jonathan C.; Miller, Joseph B.; Mitschang, Arik W.; Morgan, Douglas L.; Mossman, Amy E.; Nichols, Joy S.; Nowak, Michael A.; Plummer, David A.; Refsdal, Brian L.; Rots, Arnold H.; Siemiginowska, Aneta L.; Sundheim, Beth A.; Tibbetts, Michael S.; van Stone, David W.; Winkelman, Sherry L.; Zografou, Panagoula

2009-09-01

The first release of the Chandra Source Catalog (CSC) was published in 2009 March, and includes information about 94,676 X-ray sources detected in a subset of public ACIS imaging observations from roughly the first eight years of the Chandra mission. This release of the catalog includes point and compact sources with observed spatial extents <˜30''.The CSC is a general purpose virtual X-ray astrophysics facility that provides access to a carefully selected set of generally useful quantities for individual X-ray sources, and is designed to satisfy the needs of a broad-based group of scientists, including those who may be less familiar with astronomical data analysis in the X-ray regime.The catalog (1) provides access to the best estimates of the X-ray source properties for detected sources, with good scientific fidelity, and directly supports medium sophistication scientific analysis on using the individual source data; (2) facilitates analysis of a wide range of statistical properties for classes of X-ray sources; (3) provides efficient access to calibrated observational data and ancillary data products for individual X-ray sources, so that users can perform detailed further analysis using existing tools; and (4) includes real X-ray sources detected with flux significance greater than a predefined threshold, while maintaining the number of spurious sources at an acceptable level. For each detected X-ray source, the CSC provides commonly tabulated quantities, including source position, extent, multi-band fluxes, hardness ratios, and variability statistics, derived from the observations in which the source is detected. In addition to these traditional catalog elements, for each X-ray source the CSC includes an extensive set of file-based data products that can be manipulated interactively, including source images, event lists, light curves, and spectra from each observation in which a source is detected.

Preliminary Investigations on Therapy Thresholds for Laser Dosimetry, Cryogen Spray Cooling Duration, and Treatment Cycles for Laser Cartilage Reshaping in the New Zealand White Rabbit Auricle

PubMed Central

Chlebicki, Cara A.; Protsenko, Dmitry E.; Wong, Brian J.

2014-01-01

Previous studies have demonstrated the feasibility of laser irradiation (λ=1.45 μm) in tandem with cryogen spray cooling (CSC) to reshape rabbit auricular cartilage using total energy density of 14 J/cm2. The aim of this study was to further explore and identify the dosimetry parameter space for laser output energy, CSC duration, and treatment cycles required to achieve shape change while limiting skin and cartilage injury. Ten New Zealand white rabbits were treated with the 1.45 μm diode laser combined with cryogen spray cooling (Candela Smoothbeam™, Candela Co., Wayland, MA). The ear's central portion was bent around a cylindrical jig and irradiated in consecutive spots of 6 mm diameter (13 J/cm2 or 14 J/cm2 per spot) along 3 rows encompassing the bend. CSC was delivered during irradiation in cycles consisting of 25-35 ms. At thin and thick portions of the ear, 4-7 and 6-10 treatment cycles were delivered, respectively. After surgery, ears were examined and splinted for 6 weeks. Treatment parameters resulting in acceptable (Grades 1 & 2) and unacceptable (Grade 3) skin injuries for thick and thin regions were identified and shape change was observed. Confocal and histological analysis of cartilage tissue revealed several outcomes correlating to laser dosimetry, CSC duration, and treatment cycles. These outcomes included expansion of cartilage layers (thickening), partial cartilage injuries, and full thickness cartilage injuries. We determined therapy thresholds for laser output energy, cryogen spray cooling duration, and treatment cycles in the rabbit auricular model. These parameters are a starting point for future clinical procedures aimed at correcting external ear deformities. PMID:24202858

Photoreceptor layer map using spectral-domain optical coherence tomography.

PubMed

Lee, Ji Eun; Lim, Dae Won; Bae, Han Yong; Park, Hyun Jin

2009-12-01

To develop a novel method for analysis of the photoreceptor layer map (PLM) generated using spectral-domain optical coherence tomography (OCT). OCT scans were obtained from 20 eyes, 10 with macular holes (MH) and 10 with central serous chorioretinopathy (CSC) using the Macular Cube (512 x 128) protocol of the Cirrus HD-OCT (Carl Zeiss). The scanned data were processed using embedded tools of the advanced visualization. A partial thickness OCT fundus image of the photoreceptor layer was generated by setting the region of interest to a 50-microm thick layer that was parallel and adjacent to the retinal pigment epithelium. The resulting image depicted the photoreceptor layer as a map of the reflectivity in OCT. The PLM was compared with fundus photography, auto-fluorescence, tomography, and retinal thickness map. The signal from the photoreceptor layer of every OCT scan in each case was demonstrated as a single image of PLM in a fundus photograph fashion. In PLM images, detachment of the sensory retina is depicted as a hypo-reflective area, which represents the base of MH and serous detachment in CSC. Relative hypo-reflectivity, which was also noted at closed MH and at recently reattached retina in CSC, was associated with reduced signal from the junction between the inner and outer segments of photoreceptors in OCT images. Using PLM, changes in the area of detachment and reflectivity of the photoreceptor layer could be efficiently monitored. The photoreceptor layer can be analyzed as a map using spectral-domain OCT. In the treatment of both MH and CSC, PLM may provide new pathological information about the photoreceptor layer to expand our understanding of these diseases.

Multilevel Safety Climate and Safety Performance in the Construction Industry: Development and Validation of a Top-Down Mechanism

PubMed Central

Gao, Ran; Chan, Albert P.C.; Utama, Wahyudi P.; Zahoor, Hafiz

2016-01-01

The character of construction projects exposes front-line workers to dangers and accidents. Safety climate has been confirmed to be a predictor of safety performance in the construction industry. This study aims to explore the underlying mechanisms of the relationship between multilevel safety climate and safety performance. An integrated model was developed to study how particular safety climate factors of one level affect those of other levels, and then affect safety performance from the top down. A questionnaire survey was administered on six construction sites in Vietnam. A total of 1030 valid questionnaires were collected from this survey. Approximately half of the data were used to conduct exploratory factor analysis (EFA) and the remaining data were submitted to structural equation modeling (SEM). Top management commitment (TMC) and supervisors’ expectation (SE) were identified as factors to represent organizational safety climate (OSC) and supervisor safety climate (SSC), respectively, and coworkers’ caring and communication (CCC) and coworkers’ role models (CRM) were identified as factors to denote coworker safety climate (CSC). SEM results show that OSC factor is positively related to SSC factor and CSC factors significantly. SSC factor could partially mediate the relationship between OSC factor and CSC factors, as well as the relationship between OSC factor and safety performance. CSC factors partially mediate the relationship between OSC factor and safety performance, and the relationship between SSC factor and safety performance. The findings imply that a positive safety culture should be established both at the organizational level and the group level. Efforts from all top management, supervisors, and coworkers should be provided to improve safety performance in the construction industry. PMID:27834823

An improved survivability prognosis of breast cancer by using sampling and feature selection technique to solve imbalanced patient classification data.

PubMed

Wang, Kung-Jeng; Makond, Bunjira; Wang, Kung-Min

2013-11-09

Breast cancer is one of the most critical cancers and is a major cause of cancer death among women. It is essential to know the survivability of the patients in order to ease the decision making process regarding medical treatment and financial preparation. Recently, the breast cancer data sets have been imbalanced (i.e., the number of survival patients outnumbers the number of non-survival patients) whereas the standard classifiers are not applicable for the imbalanced data sets. The methods to improve survivability prognosis of breast cancer need for study. Two well-known five-year prognosis models/classifiers [i.e., logistic regression (LR) and decision tree (DT)] are constructed by combining synthetic minority over-sampling technique (SMOTE), cost-sensitive classifier technique (CSC), under-sampling, bagging, and boosting. The feature selection method is used to select relevant variables, while the pruning technique is applied to obtain low information-burden models. These methods are applied on data obtained from the Surveillance, Epidemiology, and End Results database. The improvements of survivability prognosis of breast cancer are investigated based on the experimental results. Experimental results confirm that the DT and LR models combined with SMOTE, CSC, and under-sampling generate higher predictive performance consecutively than the original ones. Most of the time, DT and LR models combined with SMOTE and CSC use less informative burden/features when a feature selection method and a pruning technique are applied. LR is found to have better statistical power than DT in predicting five-year survivability. CSC is superior to SMOTE, under-sampling, bagging, and boosting to improve the prognostic performance of DT and LR.

An improved survivability prognosis of breast cancer by using sampling and feature selection technique to solve imbalanced patient classification data

PubMed Central

2013-01-01

Background Breast cancer is one of the most critical cancers and is a major cause of cancer death among women. It is essential to know the survivability of the patients in order to ease the decision making process regarding medical treatment and financial preparation. Recently, the breast cancer data sets have been imbalanced (i.e., the number of survival patients outnumbers the number of non-survival patients) whereas the standard classifiers are not applicable for the imbalanced data sets. The methods to improve survivability prognosis of breast cancer need for study. Methods Two well-known five-year prognosis models/classifiers [i.e., logistic regression (LR) and decision tree (DT)] are constructed by combining synthetic minority over-sampling technique (SMOTE) ,cost-sensitive classifier technique (CSC), under-sampling, bagging, and boosting. The feature selection method is used to select relevant variables, while the pruning technique is applied to obtain low information-burden models. These methods are applied on data obtained from the Surveillance, Epidemiology, and End Results database. The improvements of survivability prognosis of breast cancer are investigated based on the experimental results. Results Experimental results confirm that the DT and LR models combined with SMOTE, CSC, and under-sampling generate higher predictive performance consecutively than the original ones. Most of the time, DT and LR models combined with SMOTE and CSC use less informative burden/features when a feature selection method and a pruning technique are applied. Conclusions LR is found to have better statistical power than DT in predicting five-year survivability. CSC is superior to SMOTE, under-sampling, bagging, and boosting to improve the prognostic performance of DT and LR. PMID:24207108

Coordination of self-renewal in glioblastoma by integration of adhesion and microRNA signaling.

PubMed

Alvarado, Alvaro G; Turaga, Soumya M; Sathyan, Pratheesh; Mulkearns-Hubert, Erin E; Otvos, Balint; Silver, Daniel J; Hale, James S; Flavahan, William A; Zinn, Pascal O; Sinyuk, Maksim; Li, Meizhang; Guda, Maheedhara R; Velpula, Kiran K; Tsung, Andrew J; Nakano, Ichiro; Vogelbaum, Michael A; Majumder, Sadhan; Rich, Jeremy N; Lathia, Justin D

2016-05-01

Cancer stem cells (CSCs) provide an additional layer of complexity for tumor models and targets for therapeutic development. The balance between CSC self-renewal and differentiation is driven by niche components including adhesion, which is a hallmark of stemness. While studies have demonstrated that the reduction of adhesion molecules, such as integrins and junctional adhesion molecule-A (JAM-A), decreases CSC maintenance. The molecular circuitry underlying these interactions has yet to be resolved. MicroRNA screening predicted that microRNA-145 (miR-145) would bind to JAM-A. JAM-A overexpression in CSCs was evaluated both in vitro (proliferation and self-renewal) and in vivo (intracranial tumor initiation). miR-145 introduction into CSCs was similarly assessed in vitro. Additionally, The Cancer Genome Atlas dataset was evaluated for expression levels of miR-145 and overall survival of the different molecular groups. Using patient-derived glioblastoma CSCs, we confirmed that JAM-A is suppressed by miR-145. CSCs expressed low levels of miR-145, and its introduction decreased self-renewal through reductions in AKT signaling and stem cell marker (SOX2, OCT4, and NANOG) expression; JAM-A overexpression rescued these effects. These findings were predictive of patient survival, with a JAM-A/miR-145 signature robustly predicting poor patient prognosis. Our results link CSC-specific niche signaling to a microRNA regulatory network that is altered in glioblastoma and can be targeted to attenuate CSC self-renewal. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Sorption of vanadium (V) onto natural soil colloids under various solution pH and ionic strength conditions.

PubMed

Luo, Xiuhua; Yu, Lin; Wang, Changzhao; Yin, Xianqiang; Mosa, Ahmed; Lv, Jialong; Sun, Huimin

2017-02-01

Batch sorption kinetics and isothermal characteristics of V(V) were investigated on three natural soil colloids (manual loessial soil colloid (MSC), aeolian sandy soil colloid (ASC), and cultivated loessial soil colloid (CSC)) under various solution pH and ionic strength (IS) conditions. Colloids were characterized by atomic force microscopy (AFM), X-ray diffraction (XRD), and fourier transform infrared spectroscopy (FTIR). AFM micrographs showed CSC with an aggregated shape with larger particle diameter as compared with ASC and MSC. XRD spectra revealed the presence of different minerals in natural soil colloids including biotite, kaolinite, calcite and quartz, which might contribute to sorption process. The sorption ability decreased with increase of colloidal particle size. The sorption was mainly attributed to complexation by active carboxylate and alcohol groups of colloidal components. Sorption kinetics and isotherms of V(V) onto natural soil colloids were best fitted with Pseudo-second-order and Freundlich models. Langmuir model indicated that sorption capacity of MSC and ASC was comparable (285.7 and 238.1 mg g -1 ); however, CSC exhibited the lowest sorption capacity (41.5 mg g -1 ) due to its larger particle diameter and aggregated shape. The maximum V(V) sorption capacity reached plateau values at a solution pH ranged between 5.0 and 9.0 for MSC and ASC, and 6.0-8.0 for CSC. Sorption capacity of V(V) onto natural soil colloids decreased with increasing IS. Based on result of this study we can conclude that sorption of V(V) onto natural soil colloids is pH- and IS-dependent. These findings provide insights on the remediation of vanadium-contaminated soils. Copyright © 2016 Elsevier Ltd. All rights reserved.

Nanoparticles increase the efficacy of cancer chemopreventive agents in cells exposed to cigarette smoke condensate.

PubMed

Pulliero, Alessandra; Wu, Yun; Fenoglio, Daniela; Parodi, Alessia; Romani, Massimo; Soares, Christiane P; Filaci, Gilberto; Lee, James L; Sinkam, Patrick N; Izzotti, Alberto

2015-03-01

Lung cancer is a leading cause of death in developed countries. Although smoking cessation is a primary strategy for preventing lung cancer, former smokers remain at high risk of cancer. Accordingly, there is a need to increase the efficacy of lung cancer prevention. Poor bioavailability is the main factor limiting the efficacy of chemopreventive agents. The aim of this study was to increase the efficacy of cancer chemopreventive agents by using lipid nanoparticles (NPs) as a carrier. This study evaluated the ability of lipid NPs to modify the pharmacodynamics of chemopreventive agents including N-acetyl-L-cysteine, phenethyl isothiocyanate and resveratrol (RES). The chemopreventive efficacy of these drugs was determined by evaluating their abilities to counteract cytotoxic damage (DNA fragmentation) induced by cigarette smoke condensate (CSC) and to activate protective apoptosis (annexin-V cytofluorimetric staining) in bronchial epithelial cells both in vitro and in ex vivo experiment in mice. NPs decreased the toxicity of RES and increased its ability to counteract CSC cytotoxicity. NPs significantly increased the ability of phenethyl isothiocyanate to attenuate CSC-induced DNA fragmentation at the highest tested dose. In contrast, this potentiating effect was observed at all tested doses of RES, NPs dramatically increasing RES-induced apoptosis in CSC-treated cells. These results provide evidence that NPs are highly effective at increasing the efficacy of lipophilic drugs (RES) but are not effective towards hydrophilic agents (N-acetyl-L-cysteine), which already possess remarkable bioavailability. Intermediate effects were observed for phenethyl isothiocyanate. These findings are relevant to the identification of cancer chemopreventive agents that would benefit from lipid NP delivery. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Analysis of WC/Ni-Based Coatings Deposited by Controlled Short-Circuit MIG Welding

NASA Astrophysics Data System (ADS)

Vespa, P.; Pinard, P. T.; Gauvin, R.; Brochu, M.

2012-06-01

This study investigates the recently developed controlled short-circuit metal inert gas (CSC-MIG) welding system for depositing WC/Ni-based claddings on carbon steel substrates. WC/Ni-based coatings deposited by CSC-MIG were analyzed by optical light microscopy and scanning electron microscopy (SEM) equipped with energy dispersive spectroscopy (EDS) and electron backscatter diffraction (EBSD) capabilities. X-ray diffraction (XRD) and hardness measurements of depositions are also reported. The CSC-MIG welding system provides a significant amount of user control over the current waveform during welding and has lower heat input when compared with traditional MIG welding. Heat input for the analyzed coatings ranged from 10.1 to 108.7 J/mm. Metallurgically bonded coatings free from spatter and with 0.75% average porosity were produced. It was found that the detrimental decarburization of the WC particles seen in thermal spray systems does not occur when welding with the CSC-MIG. Precipitation of a reaction layer around the reinforcing phase was identified as WC; the average thickness of which increases from 3.8 to 7.2 μm for the low and high heat input condition, respectively. Precipitation of newly formed WC particles was observed; their size distribution increased from D 50 of 2.4 μm in the low heat input weldment to 6.75 μm in the high heat input weldment. The level of dilution of the reinforcing phase increases significantly with heat input. The hardness of the deposited coatings decreases from 587 HV10 to 410 HV10 when the energy input was increased from 10.1 to 108.7 J/mm.

Preliminary investigations on therapy thresholds for laser dosimetry, cryogen spray cooling duration, and treatment cycles for laser cartilage reshaping in the New Zealand white rabbit auricle.

PubMed

Chlebicki, Cara A; Protsenko, Dmitry E; Wong, Brian J

2014-05-01

Previous studies have demonstrated the feasibility of laser irradiation (λ = 1.45 μm) in tandem with cryogen spray cooling (CSC) to reshape rabbit auricular cartilage using a total energy density of 14 J/cm(2). The aim of this study was to further explore and identify the dosimetry parameter space for laser output energy, CSC duration, and treatment cycles required to achieve shape change while limiting skin and cartilage injury. Ten New Zealand white rabbits were treated with the 1.45 μm diode laser combined with cryogen spray cooling (Candela Smoothbeam™, Candela Co., Wayland, MA, USA). The ear's central portion was bent around a cylindrical jig and irradiated in consecutive spots of 6 mm diameter (13 or 14 J/cm(2) per spot) along three rows encompassing the bend. CSC was delivered during irradiation in cycles consisting of 25-35 ms. At thin and thick portions of the ear, 4-7 and 6-10 treatment cycles were delivered, respectively. After surgery, ears were examined and splinted for 6 weeks. Treatment parameters resulting in acceptable (grades 1 and 2) and unacceptable (grade 3) skin injuries for thick and thin regions were identified, and shape change was observed. Confocal and histological analysis of cartilage tissue revealed several outcomes correlating to laser dosimetry, CSC duration, and treatment cycles. These outcomes included expansion of cartilage layers (thickening), partial cartilage injuries, and full-thickness cartilage injuries. We determined therapy thresholds for laser output energy, cryogen spray cooling duration, and treatment cycles in the rabbit auricular model. These parameters are a starting point for future clinical procedures aimed at correcting external ear deformities.