WorldWideScience

Sample records for causeway immigration checkpoint

  1. Exposure to methyl tert-butyl ether, benzene, and total hydrocarbons at the Singapore-Malaysia causeway immigration checkpoint

    Energy Technology Data Exchange (ETDEWEB)

    Tan, C.; Ong, H.Y.; Kok, P.W. [and others

    1996-12-31

    The primary aim of this study was to determine the extent and levels of exposure to volatile organic compounds (VOCs) from automobile emissions in a group of immigration officers at a busy cross-border checkpoint. A majority (80%) of the workers monitored were exposed to benzene at levels between 0.01 and 0.5 ppm, with only 1.2% exceeding the current Occupational Safety and Health Administration occupational exposure limit of 1 ppm. The geometric mean (GM) concentrations of 8-hr time-weighted average exposure were 0.03 ppm, 0.9 ppm, and 2.46 ppm for methyl-tert-butyl ether (MTBE), benzene, and total hydrocarbons (THC), respectively. The highest time-weighted average concentrations measured were 1.05 ppm for MTBE, 2.01 ppm for benzene, and 34 ppm for THC. It was found that motorbikes emitted a more significant amount of pollutants compared with motor cars. On average, officers at the motorcycle booths were exposed to four to five times higher levels of VOCs (GMs of 0.07 ppm, 0.23 ppm, and 4.7 ppm for MTBE, benzene, and THC) than their counterparts at the motor car booths (GMs of 0.01 ppm, 0.05 ppm, and 1.5 ppm). The airborne concentrations of all three pollutants correlated with the flow of vehicle traffic. Close correlations were also noted for the concentrations in ambient air for the three pollutants measured. Benzene and MTBE had a correlation coefficient of 0.97. The overall findings showed that the concentrations of various VOCs were closely related to the traffic density, suggesting that they were from a common source, such as exhaust emissions from the vehicles. The results also indicated that although benzene, MTBE, and THC are known to be volatile, a significant amount could still be detected in the ambient environment, thus contributing to our exposure to these compounds. 4 refs., 6 figs.

  2. Effects of causeway construction on vegetation and sedimentation in North Carolina tidal marshes

    Science.gov (United States)

    Knowlton, A.; Leonard, L.; Pricope, N. G.; Eulie, D.

    2017-12-01

    Causeways, especially those constructed to facilitate transportation across low lying tidal marshes, are known to affect tidal exchanges and thereby potentially influence geological and biological processes in these ecosystems. While these impacts have been documented in several expansive marsh systems with large tidal ranges, the extent of these impacts in smaller tidal creek watersheds is less understood. This study examined how the presence, absence, and removal of small causeways affected sedimentological processes and vegetation characteristics in two small tidal creek watersheds in Wilmington, NC. Surficial deposition rates, determined using petri-dish sediment traps, indicate that mean deposition landward of a small causeway (1.64 mg cm-2day-1) is significantly lower (pchanges adjacent to the causeway. Partial causeway removal in one of these systems in 2006 also provided the opportunity to evaluate how the marsh canopy responded to causeway removal. Using Juncus roemerianus and Spartina alterniflora as a proxy for changes in tidal exchange, spectroradiometer data and aerial imagery available in 2006 and 2016 will be used to quantify changes in canopy coverage subsequent to causeway removal. Although this study is ongoing, the preliminary results indicate that small causeways, similar to their larger counterparts, significantly affect the rate and characteristics of sediment delivered to landward marshes and also affect tidal exchanges that lead to changes in vegetation characteristics.

  3. Prudhoe Bay causeways and the summer coastal movements of arctic cisco and least cisco

    International Nuclear Information System (INIS)

    Fechhelm, R.G.; Martin, L.R.; Gallaway, B.J.; Wilson, W.J.; Griffiths, W.B.

    1999-01-01

    The possible effects that two Prudhoe Bay causeways (the West Dock and the Endicott Causeways) may have on the alongshore feeding dispersal and migration of least cisco and arctic cisco from their overwintering grounds in the Colville River were analyzed. The gravel causeways, which extends seaward from the coast, are used as platforms in recovering offshore petroleum reserves and extracting seawater that is injected into subsurface oil reservoirs. Part 1 of the paper analyzed catch data for juvenile least cisco collected during the summers from 1985 to 1993. Part 2 of the paper used data from several mark-recapture studies to analyze rates of tag recovery in a Colville River commercial gill net fishery for subadult and adult ciscos. It was determined that during two of the four years in which juvenile least cisco were abundant in the study area, catch rates were much lower east of West Dock. This suggests that small fish traveling eastward along the coast failed to bypass the West Dock causeway. However, no such disparities were found in the Endicott Causeway. During the nine year study, the rates of release were examined for three areas of release. The contradicting effects of the two causeways were discussed in terms of their design and location. The West Dock was constructed within the dispersal range of a diadromous species, at the eastern end of a brackish-water lagoon system. The Endicott Causeway was constructed on a shallow-water shelf, was fitted with breaches and is constantly receiving freshwater discharge from the Sagavanirktok River. 44 refs., 3 tabs., 9 figs

  4. INSAR AND FINITE ELEMENT ANALYSIS OF GROUND DEFORMATION AT LAKE URMIA CAUSEWAY (LUC, NORTHWEST IRAN

    Directory of Open Access Journals (Sweden)

    R. Shamshiri

    2013-09-01

    Full Text Available Precise long-term deformation monitoring of causeways and bridges is of vital task for maintenance and management work related to transportation safety. In this study, we analyse the settlement of Lake Urmia Causeway (LUC, northwest Iran, using observations from InSAR and Finite Element Model (FEM simulation. For InSAR processing, we analyse 58 SAR images of ENVISAT, ALOS and TerraSAR-X (TSX using the SBAS technique to assess the settlement of embankments in the years 2003–2013. The InSAR results show deflation on both embankments with a peak velocity of > 5 cm/year in the satellite Line Of Sight (LOS direction. The InSAR observations are then used to construct a settlement compaction model for the cross section at the distance of 4 km from the most western edge of the causeway, using a 2D Finite Element Model. Our FEM results suggest that settlement of the embankments will continue in the future due to consolidation phenomenon.

  5. Inputs and internal cycling of nitrogen to a causeway influenced, hypersaline lake, Great Salt Lake, Utah, USA

    Science.gov (United States)

    Naftz, David L.

    2017-01-01

    Nitrogen inputs to Great Salt Lake (GSL), located in the western USA, were quantified relative to the resident nitrogen mass in order to better determine numeric nutrient criteria that may be considered at some point in the future. Total dissolved nitrogen inputs from four surface-water sources entering GSL were modeled during the 5-year study period (2010–2014) and ranged from 1.90 × 106 to 5.56 × 106 kg/year. The railroad causeway breach was a significant conduit for the export of dissolved nitrogen from Gilbert to Gunnison Bay, and in 2011 and 2012, net losses of total nitrogen mass from Gilbert Bay via the Causeway breach were 9.59 × 105 and 1.51 × 106 kg. Atmospheric deposition (wet + dry) was a significant source of nitrogen to Gilbert Bay, exceeding the dissolved nitrogen load contributed via the Farmington Bay causeway surface-water input by >100,000 kg during 2 years of the study. Closure of two railroad causeway culverts in 2012 and 2013 likely initiated a decreasing trend in the volume of the higher density Deep Brine Layer and associated declines in total dissolved nitrogen mass contained in this layer. The large dissolved nitrogen pool in Gilbert Bay relative to the amount of nitrogen contributed by surface-water inflow sources is consistent with the terminal nature of GSL and the predominance of internal nutrient cycling. The opening of the new railroad causeway breach in 2016 will likely facilitate more efficient bidirectional flow between Gilbert and Gunnison Bays, resulting in potentially substantial changes in nutrient pools within GSL.

  6. Efficient Incremental Checkpointing of Java Programs

    DEFF Research Database (Denmark)

    Lawall, Julia Laetitia; Muller, Gilles

    2000-01-01

    This paper investigates the optimization of language-level checkpointing of Java programs. First, we describe how to systematically associate incremental checkpoints with Java classes. While being safe, the genericness of this solution induces substantial execution overhead. Second, to solve...

  7. Network support for system initiated checkpoints

    Science.gov (United States)

    Chen, Dong; Heidelberger, Philip

    2013-01-29

    A system, method and computer program product for supporting system initiated checkpoints in parallel computing systems. The system and method generates selective control signals to perform checkpointing of system related data in presence of messaging activity associated with a user application running at the node. The checkpointing is initiated by the system such that checkpoint data of a plurality of network nodes may be obtained even in the presence of user applications running on highly parallel computers that include ongoing user messaging activity.

  8. Checkpointing for a hybrid computing node

    Science.gov (United States)

    Cher, Chen-Yong

    2016-03-08

    According to an aspect, a method for checkpointing in a hybrid computing node includes executing a task in a processing accelerator of the hybrid computing node. A checkpoint is created in a local memory of the processing accelerator. The checkpoint includes state data to restart execution of the task in the processing accelerator upon a restart operation. Execution of the task is resumed in the processing accelerator after creating the checkpoint. The state data of the checkpoint are transferred from the processing accelerator to a main processor of the hybrid computing node while the processing accelerator is executing the task.

  9. Diversity of Microbial Communities and Quantitative Chemodiversity in Layers of Marine Sediment Cores from a Causeway (Kaichu-Doro in Okinawa Island, Japan

    Directory of Open Access Journals (Sweden)

    Taha Soliman

    2017-12-01

    Full Text Available Microbial community diversity and chemodiversity were investigated in marine sediments adjacent to the Okinawan “Kaichu-Doro” Causeway, which was constructed 46 years ago to connect a group of four islands (Henza-jima, Miyagi-jima, Ikei-jima, Hamahiga-jima to the Okinawan main island. This causeway was not built on pilings, but by land reclamation; hence, it now acts as a long, thin peninsula. The construction of this causeway was previously shown to have influenced the surrounding marine ecosystem, causing ecosystem fragmentation and loss of water circulation. In this study, we collected sediment cores (n = 10 from five paired sites in 1 m water depths. Each pair of sites consisted of one site each on the immediate north and south sides of the causeway. Originally the members of each pair were much closer to each other (<150 m than to other pairs, but now the members of each pair are isolated by the causeway. Each core was 60–80 cm long and was divided into 15-cm layers. We examined the vertical diversity of microbial communities and chemical compounds to determine the correlation between chemodiversity and microbial communities among marine sediment cores and layers. Principal coordinate analyses (PCoA of detected compounds and of bacterial and archaeal operational taxonomic units (OTUs revealed that the north and south sides of the causeway are relatively isolated, with each side having unique microbial OTUs. Additionally, some bacterial families (e.g., Acidaminobacteraceae, Rhizobiaceae, and Xanthomonadaceae were found only on the south side of Kaichu-Doro. Interestingly, we found that the relative abundance of OTUs for some microbial families increased from top to bottom, but this was reversed in some other families. We conclude that the causeway has altered microbial community composition and metabolite profiles in marine sediments.

  10. Diversity of Microbial Communities and Quantitative Chemodiversity in Layers of Marine Sediment Cores from a Causeway (Kaichu-Doro) in Okinawa Island, Japan.

    Science.gov (United States)

    Soliman, Taha; Reimer, James D; Yang, Sung-Yin; Villar-Briones, Alejandro; Roy, Michael C; Jenke-Kodama, Holger

    2017-01-01

    Microbial community diversity and chemodiversity were investigated in marine sediments adjacent to the Okinawan "Kaichu-Doro" Causeway, which was constructed 46 years ago to connect a group of four islands (Henza-jima, Miyagi-jima, Ikei-jima, Hamahiga-jima) to the Okinawan main island. This causeway was not built on pilings, but by land reclamation; hence, it now acts as a long, thin peninsula. The construction of this causeway was previously shown to have influenced the surrounding marine ecosystem, causing ecosystem fragmentation and loss of water circulation. In this study, we collected sediment cores ( n = 10) from five paired sites in 1 m water depths. Each pair of sites consisted of one site each on the immediate north and south sides of the causeway. Originally the members of each pair were much closer to each other (microbial communities and chemical compounds to determine the correlation between chemodiversity and microbial communities among marine sediment cores and layers. Principal coordinate analyses (PCoA) of detected compounds and of bacterial and archaeal operational taxonomic units (OTUs) revealed that the north and south sides of the causeway are relatively isolated, with each side having unique microbial OTUs. Additionally, some bacterial families (e.g., Acidaminobacteraceae, Rhizobiaceae, and Xanthomonadaceae) were found only on the south side of Kaichu-Doro. Interestingly, we found that the relative abundance of OTUs for some microbial families increased from top to bottom, but this was reversed in some other families. We conclude that the causeway has altered microbial community composition and metabolite profiles in marine sediments.

  11. Checkpoint inhibitors in breast cancer

    DEFF Research Database (Denmark)

    Polk, Anne; Svane, Inge-Marie; Andersson, Michael

    2018-01-01

    INTRODUCTION: An increasing number of compounds directed against immune checkpoints are currently under clinical development. In this review we summarize current research in breast cancer. MATERIAL AND METHODS: A computer-based literature search was carried out using PubMed and EMBASE; data...... reported at international meetings and clinicaltrials.gov were included as well. RESULTS: The obtained overall response rate of PD-1/PD-L1 monotherapy varied from 5 to 30% in heavily pretreated triple negative breast cancer (TNBC). The median duration of progression free survival and overall survival were...... and induce long standing anti-tumor immunity in a subgroup of breast cancer patients. However, the identification of predictive biomarkers is crucial for further development of this treatment modality....

  12. Asynchronous Checkpoint Migration with MRNet in the Scalable Checkpoint / Restart Library

    Energy Technology Data Exchange (ETDEWEB)

    Mohror, K; Moody, A; de Supinski, B R

    2012-03-20

    Applications running on today's supercomputers tolerate failures by periodically saving their state in checkpoint files on stable storage, such as a parallel file system. Although this approach is simple, the overhead of writing the checkpoints can be prohibitive, especially for large-scale jobs. In this paper, we present initial results of an enhancement to our Scalable Checkpoint/Restart Library (SCR). We employ MRNet, a tree-based overlay network library, to transfer checkpoints from the compute nodes to the parallel file system asynchronously. This enhancement increases application efficiency by removing the need for an application to block while checkpoints are transferred to the parallel file system. We show that the integration of SCR with MRNet can reduce the time spent in I/O operations by as much as 15x. However, our experiments exposed new scalability issues with our initial implementation. We discuss the sources of the scalability problems and our plans to address them.

  13. Molecular Mechanisms of DNA Replication Checkpoint Activation

    Directory of Open Access Journals (Sweden)

    Bénédicte Recolin

    2014-03-01

    Full Text Available The major challenge of the cell cycle is to deliver an intact, and fully duplicated, genetic material to the daughter cells. To this end, progression of DNA synthesis is monitored by a feedback mechanism known as replication checkpoint that is untimely linked to DNA replication. This signaling pathway ensures coordination of DNA synthesis with cell cycle progression. Failure to activate this checkpoint in response to perturbation of DNA synthesis (replication stress results in forced cell division leading to chromosome fragmentation, aneuploidy, and genomic instability. In this review, we will describe current knowledge of the molecular determinants of the DNA replication checkpoint in eukaryotic cells and discuss a model of activation of this signaling pathway crucial for maintenance of genomic stability.

  14. Transparent checkpointing and process migration in a distributed system

    OpenAIRE

    2004-01-01

    A distributed system for creating a checkpoint for a plurality of processes running on the distributed system. The distributed system includes a plurality of compute nodes with an operating system executing on each compute node. A checkpoint library resides at the user level on each of the compute nodes, and the checkpoint library is transparent to the operating system residing on the same compute node and to the other compute nodes. Each checkpoint library uses a windowed messaging logging p...

  15. Multiple functions of the S-phase checkpoint mediator.

    Science.gov (United States)

    Tanaka, Katsunori

    2010-01-01

    There is mounting evidence that replication defects are the major source of spontaneous genomic instability in cells, and that S-phase checkpoints are the principal defense against such instability. The S-phase checkpoint mediator protein Mrc1/Claspin mediates the checkpoint response to replication stress by facilitating phosphorylation of effector kinase by a sensor kinase. In this review, the multiple functions and the regulation of the S-phase checkpoint mediator are discussed.

  16. Checkpointing and Recovery in Distributed and Database Systems

    Science.gov (United States)

    Wu, Jiang

    2011-01-01

    A transaction-consistent global checkpoint of a database records a state of the database which reflects the effect of only completed transactions and not the results of any partially executed transactions. This thesis establishes the necessary and sufficient conditions for a checkpoint of a data item (or the checkpoints of a set of data items) to…

  17. Targeting the Checkpoint to Kill Cancer Cells

    Czech Academy of Sciences Publication Activity Database

    Benada, Jan; Macůrek, Libor

    2015-01-01

    Roč. 6, č. 3 (2015), s. 1912-1937 ISSN 2218-273X R&D Projects: GA ČR(CZ) GA14-34264S Institutional support: RVO:68378050 Keywords : checkpoint * DNA damage response * cancer Subject RIV: EB - Genetics ; Molecular Biology

  18. Immune mediated neuropathy following checkpoint immunotherapy.

    Science.gov (United States)

    Gu, Yufan; Menzies, Alexander M; Long, Georgina V; Fernando, S L; Herkes, G

    2017-11-01

    Checkpoint immunotherapy has revolutionised cancer therapy and is now standard treatment for many malignancies including metastatic melanoma. Acute inflammatory neuropathies, often labelled as Guillain-Barre syndrome, are an uncommon but potentially severe complication of checkpoint immunotherapy with individual cases described but never characterised as a group. We describe a case of acute sensorimotor and autonomic neuropathy following a single dose of combination ipilimumab and nivolumab for metastatic melanoma. A literature search was performed, identifying 14 other cases of acute neuropathy following checkpoint immunotherapy, with the clinical, electrophysiological and laboratory features summarised. Most cases described an acute sensorimotor neuropathy (92%) with hyporeflexia (92%) that could occur from induction up till many weeks after the final dose of therapy. In contrast to Guillain-Barre syndrome, the cerebrospinal fluid (CSF) analysis often shows a lymphocytic picture (50%) and the electrophysiology showed an axonal pattern (55%). Treatment was variable and often in combination. 11 cases received steroid therapy with only 1 death within this group, whereas of the 4 patients who did not receive steroid therapy there were 3 deaths. In conclusion checkpoint immunotherapy - induced acute neuropathies are distinct from and progress differently to Guillain-Barre syndrome. As with other immunotherapy related adverse events corticosteroid therapy should be initiated in addition to usual therapy. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Detailed Modeling and Evaluation of a Scalable Multilevel Checkpointing System

    Energy Technology Data Exchange (ETDEWEB)

    Mohror, Kathryn [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Moody, Adam [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Bronevetsky, Greg [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); de Supinski, Bronis R. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2014-09-01

    High-performance computing (HPC) systems are growing more powerful by utilizing more components. As the system mean time before failure correspondingly drops, applications must checkpoint frequently to make progress. But, at scale, the cost of checkpointing becomes prohibitive. A solution to this problem is multilevel checkpointing, which employs multiple types of checkpoints in a single run. Moreover, lightweight checkpoints can handle the most common failure modes, while more expensive checkpoints can handle severe failures. We designed a multilevel checkpointing library, the Scalable Checkpoint/Restart (SCR) library, that writes lightweight checkpoints to node-local storage in addition to the parallel file system. We present probabilistic Markov models of SCR's performance. We show that on future large-scale systems, SCR can lead to a gain in machine efficiency of up to 35 percent, and reduce the load on the parallel file system by a factor of two. In addition, we predict that checkpoint scavenging, or only writing checkpoints to the parallel file system on application termination, can reduce the load on the parallel file system by 20 × on today's systems and still maintain high application efficiency.

  20. Immigrant Enhoming

    DEFF Research Database (Denmark)

    Fogelman, Tatiana

    the difficulties that integration practitioners encounter in their attempts. I then highlight how the initial necessity of social spaces that are culturally and linguistically familiar to recent immigrants has, in conjunction with other factors, led to the establishment of at times solidified Russian-language...... fieldwork in socio-economically marginalized neighborhoods of eastern Berlin-Marzahn which are a home to a large number of Russian-speaking immigrants of German origin, I examine these projects’ attempts to construct communal social spaces shared by migrants and local residents. I start by noting...

  1. Extending the Binomial Checkpointing Technique for Resilience

    Energy Technology Data Exchange (ETDEWEB)

    Walther, Andrea; Narayanan, Sri Hari Krishna

    2016-10-10

    In terms of computing time, adjoint methods offer a very attractive alternative to compute gradient information, re- quired, e.g., for optimization purposes. However, together with this very favorable temporal complexity result comes a memory requirement that is in essence proportional with the operation count of the underlying function, e.g., if algo- rithmic differentiation is used to provide the adjoints. For this reason, checkpointing approaches in many variants have become popular. This paper analyzes an extension of the so-called binomial approach to cover also possible failures of the computing systems. Such a measure of precaution is of special interest for massive parallel simulations and adjoint calculations where the mean time between failure of the large scale computing system is smaller than the time needed to complete the calculation of the adjoint information. We de- scribe the extensions of standard checkpointing approaches required for such resilience, provide a corresponding imple- mentation and discuss numerical results.

  2. Immune checkpoint inhibitors for metastatic bladder cancer.

    Science.gov (United States)

    Massari, Francesco; Di Nunno, Vincenzo; Cubelli, Marta; Santoni, Matteo; Fiorentino, Michelangelo; Montironi, Rodolfo; Cheng, Liang; Lopez-Beltran, Anto; Battelli, Nicola; Ardizzoni, Andrea

    2018-03-01

    Chemotherapy has represented the standard therapy for unresectable or metastatic urothelial carcinoma for more than 20 years. The growing knowledge of the interaction between tumour and immune system has led to the advent of new classes of drugs, the immune-checkpoints inhibitors, which are intended to change the current scenario. To date, immunotherapy is able to improve the overall responses and survival. Moreover, thanks to its safety profile immune-checkpoint inhibitors could be proposed also to patients unfit for standard chemotherapy. No doubts that these agents have started a revolution expected for years, but despite this encouraging results it appears clear that not all subjects respond to these agents and requiring the development of reliable predictive response factors able to isolate patients who can more benefit from these treatments as well as new strategies aimed to improve immunotherapy clinical outcome. In this review we describe the active or ongoing clinical trials involving Programmed Death Ligand 1 (PD-L1), Programmed Death receptor 1 (PD-1) and Cytotoxic-T Lymphocyte Antigen 4 (CTLA 4) inhibitors in urothelial carcinoma focusing our attention on the developing new immune-agents and combination strategies with immune-checkpoint inhibitors. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Advances of Immune Checkpoint Inhibitors in Tumor Immunotherapy

    Science.gov (United States)

    Guo, Qiao

    2018-01-01

    Immune checkpoints are cell surface molecules that can fine-tune the immune responses, they are crucial for modulating the duration and amplitude of immune reactions while maintaining self-tolerance in order to minimize autoimmune responses. Numerous studies have demonstrated that tumors cells can directly express immune-checkpoint molecules, or induce many inhibitory molecules expression in the tumor microenvironment to inhibit the anti-tumor immunity. Releasing these brakes has emerged as an exciting strategy to cure cancer. In the past few years, clinical trials with therapeutic antibodies targeting to the checkpoint molecules CTLA-4 and PD-1 have rekindled the hope for cancer immunotherapy. In contrast to the conventional treatment, checkpoint inhibitors induce broad and durable antitumor responses. In the future, treatment may involve combination therapy to target different checkpoint molecules and stages of the adaptive immune responses. In this review, we summarized the recent advances of the study and development of other checkpoint molecules in tumor immunotherapy.

  4. Template based parallel checkpointing in a massively parallel computer system

    Science.gov (United States)

    Archer, Charles Jens [Rochester, MN; Inglett, Todd Alan [Rochester, MN

    2009-01-13

    A method and apparatus for a template based parallel checkpoint save for a massively parallel super computer system using a parallel variation of the rsync protocol, and network broadcast. In preferred embodiments, the checkpoint data for each node is compared to a template checkpoint file that resides in the storage and that was previously produced. Embodiments herein greatly decrease the amount of data that must be transmitted and stored for faster checkpointing and increased efficiency of the computer system. Embodiments are directed to a parallel computer system with nodes arranged in a cluster with a high speed interconnect that can perform broadcast communication. The checkpoint contains a set of actual small data blocks with their corresponding checksums from all nodes in the system. The data blocks may be compressed using conventional non-lossy data compression algorithms to further reduce the overall checkpoint size.

  5. Enhancing Immune Checkpoint Inhibitor Therapy in Kidney Cancer

    Science.gov (United States)

    2017-10-01

    AWARD NUMBER: W81XWH-15-1-0141 TITLE: Enhancing Immune Checkpoint Inhibitor therapy in Kidney Cancer PRINCIPAL INVESTIGATOR: Hans-Joerg Hammers...SUBTITLE Enhancing Immune Checkpoint Inhibitor therapy in Kidney Cancer 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH- 15-1-0141 5c. PROGRAM ELEMENT NUMBER...immune checkpoint inhibition in kidney cancer . The work is designed to test different strategies to induce or enhance the abscopal in a kidney cancer

  6. Hypoxia‐induced alterations of G2 checkpoint regulators

    OpenAIRE

    Hasvold, Grete; Lund-Andersen, Christin; Lando, Malin; Patzke, Sebastian; Hauge, Sissel; Suo, ZhenHe; Lyng, Heidi; Syljuåsen, Randi G.

    2016-01-01

    Hypoxia promotes an aggressive tumor phenotype with increased genomic instability, partially due to downregulation of DNA repair pathways. However, genome stability is also surveilled by cell cycle checkpoints. An important issue is therefore whether hypoxia also can influence the DNA damage‐induced cell cycle checkpoints. Here, we show that hypoxia (24 h 0.2% O2) alters the expression of several G2 checkpoint regulators, as examined by microarray gene expression analysis and immunoblotting o...

  7. Checkpoint independence of most DNA replication origins in fission yeast

    OpenAIRE

    Mickle, Katie L; Ramanathan, Sunita; Rosebrock, Adam; Oliva, Anna; Chaudari, Amna; Yompakdee, Chulee; Scott, Donna; Leatherwood, Janet; Huberman, Joel A

    2007-01-01

    Abstract Background In budding yeast, the replication checkpoint slows progress through S phase by inhibiting replication origin firing. In mammals, the replication checkpoint inhibits both origin firing and replication fork movement. To find out which strategy is employed in the fission yeast, Schizosaccharomyces pombe, we used microarrays to investigate the use of origins by wild-type and checkpoint-mutant strains in the presence of hydroxyurea (HU), which limits the pool of deoxyribonucleo...

  8. Germany - an immigration country

    OpenAIRE

    Siebert, Horst

    2003-01-01

    Germany has about the same proportion of foreigners in its population as the United States, it is an immigration country. In a way, Germany has let immigration happen, but it did not really have an explicit immigration policy in the past. Now it has to make up its mind on its immigration policy in the future. The paper looks at the experience with immigration in the past, at the integration of foreigners and at the issues of immigration policy.

  9. Anaphase onset before complete DNA replication with intact checkpoint responses

    DEFF Research Database (Denmark)

    Torres-Rosell, Jordi; De Piccoli, Giacomo; Cordon-Preciado, Violeta

    2007-01-01

    Cellular checkpoints prevent mitosis in the presence of stalled replication forks. Whether checkpoints also ensure the completion of DNA replication before mitosis is unknown. Here, we show that in yeast smc5-smc6 mutants, which are related to cohesin and condensin, replication is delayed, most...

  10. PD-1 Checkpoint Inhibitor Associated Autoimmune Encephalitis

    Directory of Open Access Journals (Sweden)

    Stephanie Schneider

    2017-05-01

    Full Text Available Objective: To report first-hand narrative experience of autoimmune encephalitis and to briefly review currently available evidence of autoimmune encephalitis in cancer patients treated with immune checkpoint inhibitors. Setting: A case study is presented on the management of a patient who developed autoimmune encephalitis during nivolumab monotherapy occurring after 28 weeks on anti-PD-1 monotherapy (nivolumab 3 mg/kg every 2 weeks for non-small cell lung cancer. Results: No substantial improvement was observed by antiepileptic treatment. After administration of 80 mg methylprednisolone, neurologic symptoms disappeared within 24 h and the patient fully recovered. Conclusions: Immune checkpoint inhibitor treatment can lead to autoimmune encephalitis. Clinical trial data indicate a frequency of autoimmune encephalitis of ≥0.1 to <1% with a higher probability during combined or sequential anti-CTLA-4/anti-PD-1 therapy than during anti-PD-1 or anti-PD-L1 monotherapy. Further collection of evidence and translational research is warranted.

  11. PD-1 checkpoint inhibition: Toxicities and management.

    Science.gov (United States)

    Hahn, Andrew W; Gill, David M; Agarwal, Neeraj; Maughan, Benjamin L

    2017-12-01

    With the recent approval of 5 PD-1/PD-L1 inhibitors for a number of malignancies, PD-1 axis inhibition is drastically changing the treatment landscape of immunotherapy in cancer. As PD-1/PD-L1 are involved in peripheral immune tolerance, inhibition of this immune checkpoint has led to novel immune-related adverse events including colitis, hepatitis, pneumonitis, rash, and endocrinopathies among many others. In this seminar, we will analyze the incidence of immune-related adverse events for nivolumab, pembrolizumab, atezolizumab, durvalumab, and avelumab. Then, we will discuss the specific management of the most common immune-mediated adverse events including colitis, hepatitis, pneumonitis, rash, endocrinopathies, nephritis, and neurologic toxicities. Immune-related adverse events are frequently treated with immunosuppressive medication such as steroids and mycofenolate mofetil. There are specific immune-related adverse events which are frequently seen by the treating oncologist from checkpoint inhibitors. It is essential to understand the recommended treatment options to minimize toxicity and mortality from this important class of anti-neoplastic therapies. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. The New Asian Immigrants.

    Science.gov (United States)

    Wong, Morrison G.; Hirschman, Charles

    In the early 1960s, Asian immigration to the United States was severely limited. The passage of the Immigration Act of 1965 expanded Asian immigration and ended a policy of racial discrimination and exclusion. Currently, over one third of the total immigrant population to the United States is from Asia, particularly China, Japan, Korea, the…

  13. Newly Emerging Immune Checkpoints: Promises for Future Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Robert J. Torphy

    2017-12-01

    Full Text Available Cancer immunotherapy has been a great breakthrough, with immune checkpoint inhibitors leading the way. Despite the clinical effectiveness of certain immune checkpoint inhibitors, the overall response rate remains low, and the effectiveness of immunotherapies for many tumors has been disappointing. There is substantial interest in looking for additional immune checkpoint molecules that may act as therapeutic targets for cancer. Recent advances during the last decade have identified several novel immune checkpoint targets, including lymphocyte activation gene-3 (LAG-3, B and T lymphocyte attenuator (BTLA, programmed death-1 homolog (PD-1H, T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIM-3/carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1, and the poliovirus receptor (PVR-like receptors. The investigations into these molecules have generated promising results in preclinical studies. Herein, we will summarize our current progress and understanding of these newly-characterized immune checkpoints and their potential application in cancer immunotherapy.

  14. "Isogaba Maware": quality control of genome DNA by checkpoints.

    Science.gov (United States)

    Kitazono, A; Matsumoto, T

    1998-05-01

    Checkpoints maintain the interdependency of cell cycle events by permitting the onset of an event only after the completion of the preceding event. The DNA replication checkpoint induces a cell cycle arrest until the completion of the DNA replication. Similarly, the DNA damage checkpoint arrests cell cycle progression if DNA repair is incomplete. A number of genes that play a role in the two checkpoints have been identified through genetic studies in yeasts, and their homologues have been found in fly, mouse, and human. They form signaling cascades activated by a DNA replication block or DNA damage and subsequently generate the negative constraints on cell cycle regulators. The failure of these signaling cascades results in producing offspring that carry mutations or that lack a portion of the genome. In humans, defects in the checkpoints are often associated with cancer-prone diseases. Focusing mainly on the studies in budding and fission yeasts, we summarize the recent progress.

  15. Checkpoint independence of most DNA replication origins in fission yeast.

    Science.gov (United States)

    Mickle, Katie L; Ramanathan, Sunita; Rosebrock, Adam; Oliva, Anna; Chaudari, Amna; Yompakdee, Chulee; Scott, Donna; Leatherwood, Janet; Huberman, Joel A

    2007-12-19

    In budding yeast, the replication checkpoint slows progress through S phase by inhibiting replication origin firing. In mammals, the replication checkpoint inhibits both origin firing and replication fork movement. To find out which strategy is employed in the fission yeast, Schizosaccharomyces pombe, we used microarrays to investigate the use of origins by wild-type and checkpoint-mutant strains in the presence of hydroxyurea (HU), which limits the pool of deoxyribonucleoside triphosphates (dNTPs) and activates the replication checkpoint. The checkpoint-mutant cells carried deletions either of rad3 (which encodes the fission yeast homologue of ATR) or cds1 (which encodes the fission yeast homologue of Chk2). Our microarray results proved to be largely consistent with those independently obtained and recently published by three other laboratories. However, we were able to reconcile differences between the previous studies regarding the extent to which fission yeast replication origins are affected by the replication checkpoint. We found (consistent with the three previous studies after appropriate interpretation) that, in surprising contrast to budding yeast, most fission yeast origins, including both early- and late-firing origins, are not significantly affected by checkpoint mutations during replication in the presence of HU. A few origins (approximately 3%) behaved like those in budding yeast: they replicated earlier in the checkpoint mutants than in wild type. These were located primarily in the heterochromatic subtelomeric regions of chromosomes 1 and 2. Indeed, the subtelomeric regions defined by the strongest checkpoint restraint correspond precisely to previously mapped subtelomeric heterochromatin. This observation implies that subtelomeric heterochromatin in fission yeast differs from heterochromatin at centromeres, in the mating type region, and in ribosomal DNA, since these regions replicated at least as efficiently in wild-type cells as in checkpoint

  16. Checkpoint independence of most DNA replication origins in fission yeast

    Science.gov (United States)

    Mickle, Katie L; Ramanathan, Sunita; Rosebrock, Adam; Oliva, Anna; Chaudari, Amna; Yompakdee, Chulee; Scott, Donna; Leatherwood, Janet; Huberman, Joel A

    2007-01-01

    Background In budding yeast, the replication checkpoint slows progress through S phase by inhibiting replication origin firing. In mammals, the replication checkpoint inhibits both origin firing and replication fork movement. To find out which strategy is employed in the fission yeast, Schizosaccharomyces pombe, we used microarrays to investigate the use of origins by wild-type and checkpoint-mutant strains in the presence of hydroxyurea (HU), which limits the pool of deoxyribonucleoside triphosphates (dNTPs) and activates the replication checkpoint. The checkpoint-mutant cells carried deletions either of rad3 (which encodes the fission yeast homologue of ATR) or cds1 (which encodes the fission yeast homologue of Chk2). Results Our microarray results proved to be largely consistent with those independently obtained and recently published by three other laboratories. However, we were able to reconcile differences between the previous studies regarding the extent to which fission yeast replication origins are affected by the replication checkpoint. We found (consistent with the three previous studies after appropriate interpretation) that, in surprising contrast to budding yeast, most fission yeast origins, including both early- and late-firing origins, are not significantly affected by checkpoint mutations during replication in the presence of HU. A few origins (~3%) behaved like those in budding yeast: they replicated earlier in the checkpoint mutants than in wild type. These were located primarily in the heterochromatic subtelomeric regions of chromosomes 1 and 2. Indeed, the subtelomeric regions defined by the strongest checkpoint restraint correspond precisely to previously mapped subtelomeric heterochromatin. This observation implies that subtelomeric heterochromatin in fission yeast differs from heterochromatin at centromeres, in the mating type region, and in ribosomal DNA, since these regions replicated at least as efficiently in wild-type cells as in

  17. Checkpoint independence of most DNA replication origins in fission yeast

    Directory of Open Access Journals (Sweden)

    Scott Donna

    2007-12-01

    Full Text Available Abstract Background In budding yeast, the replication checkpoint slows progress through S phase by inhibiting replication origin firing. In mammals, the replication checkpoint inhibits both origin firing and replication fork movement. To find out which strategy is employed in the fission yeast, Schizosaccharomyces pombe, we used microarrays to investigate the use of origins by wild-type and checkpoint-mutant strains in the presence of hydroxyurea (HU, which limits the pool of deoxyribonucleoside triphosphates (dNTPs and activates the replication checkpoint. The checkpoint-mutant cells carried deletions either of rad3 (which encodes the fission yeast homologue of ATR or cds1 (which encodes the fission yeast homologue of Chk2. Results Our microarray results proved to be largely consistent with those independently obtained and recently published by three other laboratories. However, we were able to reconcile differences between the previous studies regarding the extent to which fission yeast replication origins are affected by the replication checkpoint. We found (consistent with the three previous studies after appropriate interpretation that, in surprising contrast to budding yeast, most fission yeast origins, including both early- and late-firing origins, are not significantly affected by checkpoint mutations during replication in the presence of HU. A few origins (~3% behaved like those in budding yeast: they replicated earlier in the checkpoint mutants than in wild type. These were located primarily in the heterochromatic subtelomeric regions of chromosomes 1 and 2. Indeed, the subtelomeric regions defined by the strongest checkpoint restraint correspond precisely to previously mapped subtelomeric heterochromatin. This observation implies that subtelomeric heterochromatin in fission yeast differs from heterochromatin at centromeres, in the mating type region, and in ribosomal DNA, since these regions replicated at least as efficiently in wild

  18. Neuromuscular complications of immune checkpoint inhibitor therapy.

    Science.gov (United States)

    Kolb, Noah A; Trevino, Christopher R; Waheed, Waqar; Sobhani, Fatemeh; Landry, Kara K; Thomas, Alissa A; Hehir, Mike

    2018-01-17

    Immune checkpoint inhibitor (ICPI) therapy unleashes the body's natural immune system to fight cancer. ICPIs improve overall cancer survival, however, the unbridling of the immune system may induce a variety of immune-related adverse events. Neuromuscular immune complications are rare but they can be severe. Myasthenia gravis and inflammatory neuropathy are the most common neuromuscular adverse events but a variety of others including inflammatory myopathy are reported. The pathophysiologic mechanism of these autoimmune disorders may differ from that of non-ICPI-related immune diseases. Accordingly, while the optimal treatment for ICPI-related neuromuscular disorders generally follows a traditional paradigm, there are important novel considerations in selecting appropriate immunosuppressive therapy. This review presents 2 new cases, a summary of neuromuscular ICPI complications, and an approach to the diagnosis and treatment of these disorders. Muscle Nerve, 2018. © 2018 Wiley Periodicals, Inc.

  19. Keeping checkpoint/restart viable for exascale systems.

    Energy Technology Data Exchange (ETDEWEB)

    Riesen, Rolf E.; Bridges, Patrick G. (IBM Research, Ireland, Mulhuddart, Dublin); Stearley, Jon R.; Laros, James H., III; Oldfield, Ron A.; Arnold, Dorian (University of New Mexico, Albuquerque, NM); Pedretti, Kevin Thomas Tauke; Ferreira, Kurt Brian; Brightwell, Ronald Brian

    2011-09-01

    Next-generation exascale systems, those capable of performing a quintillion (10{sup 18}) operations per second, are expected to be delivered in the next 8-10 years. These systems, which will be 1,000 times faster than current systems, will be of unprecedented scale. As these systems continue to grow in size, faults will become increasingly common, even over the course of small calculations. Therefore, issues such as fault tolerance and reliability will limit application scalability. Current techniques to ensure progress across faults like checkpoint/restart, the dominant fault tolerance mechanism for the last 25 years, are increasingly problematic at the scales of future systems due to their excessive overheads. In this work, we evaluate a number of techniques to decrease the overhead of checkpoint/restart and keep this method viable for future exascale systems. More specifically, this work evaluates state-machine replication to dramatically increase the checkpoint interval (the time between successive checkpoint) and hash-based, probabilistic incremental checkpointing using graphics processing units to decrease the checkpoint commit time (the time to save one checkpoint). Using a combination of empirical analysis, modeling, and simulation, we study the costs and benefits of these approaches on a wide range of parameters. These results, which cover of number of high-performance computing capability workloads, different failure distributions, hardware mean time to failures, and I/O bandwidths, show the potential benefits of these techniques for meeting the reliability demands of future exascale platforms.

  20. Prevention of DNA Rereplication Through a Meiotic Recombination Checkpoint Response

    Directory of Open Access Journals (Sweden)

    Nicole A. Najor

    2016-12-01

    Full Text Available In the budding yeast Saccharomyces cerevisiae, unnatural stabilization of the cyclin-dependent kinase inhibitor Sic1 during meiosis can trigger extra rounds of DNA replication. When programmed DNA double-strand breaks (DSBs are generated but not repaired due to absence of DMC1, a pathway involving the checkpoint gene RAD17 prevents this DNA rereplication. Further genetic analysis has now revealed that prevention of DNA rereplication also requires MEC1, which encodes a protein kinase that serves as a central checkpoint regulator in several pathways including the meiotic recombination checkpoint response. Downstream of MEC1, MEK1 is required through its function to inhibit repair between sister chromatids. By contrast, meiotic recombination checkpoint effectors that regulate gene expression and cyclin-dependent kinase activity are not necessary. Phosphorylation of histone H2A, which is catalyzed by Mec1 and the related Tel1 protein kinase in response to DSBs, and can help coordinate activation of the Rad53 checkpoint protein kinase in the mitotic cell cycle, is required for the full checkpoint response. Phosphorylation sites that are targeted by Rad53 in a mitotic S phase checkpoint response are also involved, based on the behavior of cells containing mutations in the DBF4 and SLD3 DNA replication genes. However, RAD53 does not appear to be required, nor does RAD9, which encodes a mediator of Rad53, consistent with their lack of function in the recombination checkpoint pathway that prevents meiotic progression. While this response is similar to a checkpoint mechanism that inhibits initiation of DNA replication in the mitotic cell cycle, the evidence points to a new variation on DNA replication control.

  1. Experiences with treating immigrants

    DEFF Research Database (Denmark)

    Sandhu, Sima; Bjerre, Neele V; Dauvrin, Marie

    2012-01-01

    PURPOSE: While there has been systematic research on the experiences of immigrant patients in mental health services within certain European countries, little research has explored the experiences of mental health professionals in the delivery of services to immigrants across Europe. This study...... sought to explore professionals' experiences of delivering care to immigrants in districts densely populated with immigrants across Europe. METHODS: Forty-eight semi-structured interviews were conducted with mental health care professionals working in 16 European countries. Professionals in each country...... were recruited from three areas with the highest proportion of immigrants. For the purpose of this study, immigrants were defined as first-generation immigrants born outside the country of current residence, including regular immigrants, irregular immigrants, asylum seekers, refugees and victims...

  2. Combination approaches with immune checkpoint blockade in cancer therapy

    Directory of Open Access Journals (Sweden)

    Maarten Swart

    2016-11-01

    Full Text Available In healthy individuals, immune checkpoint molecules prevent autoimmune responses and limit immune cell-mediated tissue damage. Tumors frequently exploit these molecules to evade eradication by the immune system. Over the past years, immune checkpoint blockade of cytotoxic T lymphocyte antigen-4 (CTLA-4 and programmed death-1 (PD-1 emerged as promising strategies to activate anti-tumor cytotoxic T cell responses. Although complete regression and long-term survival is achieved in some patients, not all patients respond. This review describes promising, novel combination approaches involving immune checkpoint blockade, aimed at increasing response-rates to the single treatments.

  3. Radiotherapy and immune checkpoint blockades: a snapshot in 2016

    Energy Technology Data Exchange (ETDEWEB)

    Koo, Tae Yool [Dept. of Radiation Oncology, Hallym University Chuncheon Sacred Heart Hospital, Chuncheon (Korea, Republic of); Kim, In Ah [Dept. of Radiation Oncology, Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2016-12-15

    Immune checkpoint blockades including monoclonal antibodies (mAbs) of cytotoxic T-lymphocyte antigen-4 (CTLA-4), programmed death-1 (PD-1), and programmed death-ligand 1 (PD-L1) have been emerged as a promising anticancer therapy. Several immune checkpoint blockades have been approved by US Food and Drug Administration (FDA), and have shown notable success in clinical trials for patients with advanced melanoma and non-small cell lung cancer. Radiotherapy is a promising combination partner of immune checkpoint blockades due to its potent pro-immune effect. This review will cover the current issue and the future perspectives for combined with radiotherapy and immune checkpoint blockades based upon the available preclinical and clinical data.

  4. A New Adaptive Checkpointing Strategy for Mobile Computing

    Institute of Scientific and Technical Information of China (English)

    MENChaoguang; ZUODecheng; YANGXiaozong

    2005-01-01

    Adaptive checkpointing strategy is an efficient recovery scheme, which is suitable for mobile computing system. However, all existing adaptive checkpointing schemes are not correct to recover system when failure occurs in some special period. In this paper, the issues that will lead to system inconsistency are first discussed and then a new adaptive strategy that can recover system to correct consistent state is proposed. Our algorithm improves system recovery performance because only failure process needs rollback through logging.

  5. Attitudes towards immigration

    DEFF Research Database (Denmark)

    Malchow-Møller, Nikolaj; Munch, Jakob Roland; Skaksen, Jan Rose

    2008-01-01

    Using the European Social Survey 2002/3, we develop a new test of whether economic self-interest influences people's attitudes towards immigration, exploiting that people have widely different perceptions of the consequences of immigration......Using the European Social Survey 2002/3, we develop a new test of whether economic self-interest influences people's attitudes towards immigration, exploiting that people have widely different perceptions of the consequences of immigration...

  6. Crime and immigration

    OpenAIRE

    Brian Bell

    2014-01-01

    Immigration is one of the most important policy debates in Western countries. However, one aspect of the debate is often mischaracterized by accusations that higher levels of immigration lead to higher levels of crime. The evidence, based on empirical studies of many countries, indicates that there is no simple link between immigration and crime. Crucially, the evidence points to substantial differences in the impact on property crime, depending on the labor market opportunities of immigrant ...

  7. What drives immigration amnesties?

    OpenAIRE

    Casarico, Alessandra; Facchini, Giovanni; Frattini, Tommaso

    2012-01-01

    We develop a general model of legal and illegal immigration to understand the basic tradeoffs faced by a government in the decision to implement an immigration amnesty in the presence of a selective immigration policy. We show that two channels play an important role: an amnesty is more likely the more restricted are the occupational opportunities of undocumented immigrants and the less redistributive is the welfare state. Empirical evidence based on a novel panel dataset of legalizations car...

  8. Role of the Checkpoint Clamp in DNA Damage Response

    Directory of Open Access Journals (Sweden)

    Mihoko Kai

    2013-01-01

    Full Text Available DNA damage occurs during DNA replication, spontaneous chemical reactions, and assaults by external or metabolism-derived agents. Therefore, all living cells must constantly contend with DNA damage. Cells protect themselves from these genotoxic stresses by activating the DNA damage checkpoint and DNA repair pathways. Coordination of these pathways requires tight regulation in order to prevent genomic instability. The checkpoint clamp complex consists of Rad9, Rad1 and Hus1 proteins, and is often called the 9-1-1 complex. This PCNA (proliferating cell nuclear antigen-like donut-shaped protein complex is a checkpoint sensor protein that is recruited to DNA damage sites during the early stage of the response, and is required for checkpoint activation. As PCNA is required for multiple pathways of DNA metabolism, the checkpoint clamp has also been implicated in direct roles in DNA repair, as well as in coordination of the pathways. Here we discuss roles of the checkpoint clamp in DNA damage response (DDR.

  9. Checkpoint blockade in combination with cancer vaccines.

    Science.gov (United States)

    Morse, Michael A; Lyerly, H Kim

    2015-12-16

    Checkpoint blockade, prevention of inhibitory signaling that limits activation or function of tumor antigen-specific T cells responses, is revolutionizing the treatment of many poor prognosis malignancies. Indeed monoclonal antibodies that modulate signaling through the inhibitory molecules CTLA-4 and PD-1 are now clinically available; however, many tumors, demonstrate minimal response suggesting the need for combinations with other therapeutic strategies. Because an inadequate frequency of activated tumor antigen-specific T cells in the tumor environment, the so-called non-inflamed phenotype, is observed in some malignancies, other rationale partners are modalities that lead to enhanced T cell activation (vaccines, cytokines, toll-like receptor agonists, and other anticancer therapies such as chemo-, radio- or targeted therapies that lead to release of antigen from tumors). This review will focus on preclinical and clinical data supporting the use of cancer vaccines with anti-CTLA-4 and anti-PD-1/PD-L1 antibodies. Preliminary preclinical data demonstrate enhanced antitumor activity although the results in human studies are less clear. Broader combinations of multiple immune modulators are now under study. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Phosphorylation of Minichromosome Maintenance 3 (MCM3) by Checkpoint Kinase 1 (Chk1) Negatively Regulates DNA Replication and Checkpoint Activation.

    Science.gov (United States)

    Han, Xiangzi; Mayca Pozo, Franklin; Wisotsky, Jacob N; Wang, Benlian; Jacobberger, James W; Zhang, Youwei

    2015-05-08

    Mechanisms controlling DNA replication and replication checkpoint are critical for the maintenance of genome stability and the prevention or treatment of human cancers. Checkpoint kinase 1 (Chk1) is a key effector protein kinase that regulates the DNA damage response and replication checkpoint. The heterohexameric minichromosome maintenance (MCM) complex is the core component of mammalian DNA helicase and has been implicated in replication checkpoint activation. Here we report that Chk1 phosphorylates the MCM3 subunit of the MCM complex at Ser-205 under normal growth conditions. Mutating the Ser-205 of MCM3 to Ala increased the length of DNA replication track and shortened the S phase duration, indicating that Ser-205 phosphorylation negatively controls normal DNA replication. Upon replicative stress treatment, the inhibitory phosphorylation of MCM3 at Ser-205 was reduced, and this reduction was accompanied with the generation of single strand DNA, the key platform for ataxia telangiectasia mutated and Rad3-related (ATR) activation. As a result, the replication checkpoint is activated. Together, these data provide significant insights into the regulation of both normal DNA replication and replication checkpoint activation through the novel phosphorylation of MCM3 by Chk1. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  11. Slope Failure Hazards at Basalt Geomorphosites: A Comparative Analysis of the Giant's Causeway World Heritage Site, UK and Penghu Marine Geopark, Taiwan.

    Science.gov (United States)

    Gruendemann, Ciaran; Chung Lin, Jiun; Smith, Bernard

    2010-05-01

    Columnar basalt landscapes hold a fascination that transcends geographical and cultural boundaries. It is because of this that they feature so prominently on the global register of significant geomorphosites. Arguably the most iconic of these basalt landscapes is the Giant's Causeway in Northern Ireland, a status recognized by its inscription as a World Heritage Site. Recognition at this level invariably brings visitor pressure, and with it concern as to the impact they exert on site integrity. Rarely, however, is the same overt concern expressed for the risks that such sites pose to the visitors - or not at least until disaster strikes. Yet, the very features that make these sites attractive - tall, exposed, largely unconstrained columns - render many of them intrinsically unstable, prone to catastrophic collapse and potentially hazardous to visitors. In this presentation we highlight the nature of these slope instability issues through a comparative analysis of two geographically contrasting basalt geomorphosites. Investigations of slope hazard at the Giant's Causeway have shown that many are linked to the distinctive structural characteristics and weathering patterns of flood basalts. Typically, individual flows comprise a columnar ‘colonnade', topped by a blocky ‘entablature' and separated from the flows above and below it by a structurally weaker, but often less-permeable, palaeosol that formed during periods of volcanic quiescence. The collapse of columns is often facilitated by a combination of weathering along ever-widening joints and wedging outwards by debris that falls into them. This gradual distortion of the colonnade makes columns increasingly susceptible to collapse. Often this is triggered by intense rainfall (perhaps following a dry spell) that rapidly infiltrates joints and is ponded on the underlying palaeosol. The precise nature of the failure (toppling or outwards rotation of the column base) is largely dictated by the nature of the

  12. Immigration and income inequality

    DEFF Research Database (Denmark)

    Deding, Mette; Hussain, Azhar; Jakobsen, Vibeke

    2010-01-01

    During the last two decades most Western countries have experienced increased net immigration as well as increased income inequality. This article analyzes the effects on income inequality of an increased number of immigrants in Denmark and Germany for the 20- year period 1984-2003 and how...... the impact of the increased number of immigrants differs between the two countries. We find higher inequality for immigrants than natives in Denmark but vice versa for Germany. Over the period 1984-2003, this particular inequality gap has narrowed in both countries. At the same time, the contribution...... of immigrants to overall inequality has increased, primarily caused by increased between-group inequality. The share of immigrants in the population is more important for the change in overall inequality in Denmark than in Germany, while the opposite is the case for inequality among immigrants....

  13. Checkpoint responses to replication stalling: inducing tolerance and preventing mutagenesis

    Energy Technology Data Exchange (ETDEWEB)

    Kai, Mihoko; Wang, Teresa S.-F

    2003-11-27

    Replication mutants often exhibit a mutator phenotype characterized by point mutations, single base frameshifts, and the deletion or duplication of sequences flanked by homologous repeats. Mutation in genes encoding checkpoint proteins can significantly affect the mutator phenotype. Here, we use fission yeast (Schizosaccharomyces pombe) as a model system to discuss the checkpoint responses to replication perturbations induced by replication mutants. Checkpoint activation induced by a DNA polymerase mutant, aside from delay of mitotic entry, up-regulates the translesion polymerase DinB (Pol{kappa}). Checkpoint Rad9-Rad1-Hus1 (9-1-1) complex, which is loaded onto chromatin by the Rad17-Rfc2-5 checkpoint complex in response to replication perturbation, recruits DinB onto chromatin to generate the point mutations and single nucleotide frameshifts in the replication mutator. This chain of events reveals a novel checkpoint-induced tolerance mechanism that allows cells to cope with replication perturbation, presumably to make possible restarting stalled replication forks. Fission yeast Cds1 kinase plays an essential role in maintaining DNA replication fork stability in the face of DNA damage and replication fork stalling. Cds1 kinase is known to regulate three proteins that are implicated in maintaining replication fork stability: Mus81-Eme1, a hetero-dimeric structure-specific endonuclease complex; Rqh1, a RecQ-family helicase involved in suppressing inappropriate recombination during replication; and Rad60, a protein required for recombinational repair during replication. These Cds1-regulated proteins are thought to cooperatively prevent mutagenesis and maintain replication fork stability in cells under replication stress. These checkpoint-regulated processes allow cells to survive replication perturbation by preventing stalled replication forks from degenerating into deleterious DNA structures resulting in genomic instability and cancer development.

  14. Checkpoint responses to replication stalling: inducing tolerance and preventing mutagenesis

    International Nuclear Information System (INIS)

    Kai, Mihoko; Wang, Teresa S.-F.

    2003-01-01

    Replication mutants often exhibit a mutator phenotype characterized by point mutations, single base frameshifts, and the deletion or duplication of sequences flanked by homologous repeats. Mutation in genes encoding checkpoint proteins can significantly affect the mutator phenotype. Here, we use fission yeast (Schizosaccharomyces pombe) as a model system to discuss the checkpoint responses to replication perturbations induced by replication mutants. Checkpoint activation induced by a DNA polymerase mutant, aside from delay of mitotic entry, up-regulates the translesion polymerase DinB (Polκ). Checkpoint Rad9-Rad1-Hus1 (9-1-1) complex, which is loaded onto chromatin by the Rad17-Rfc2-5 checkpoint complex in response to replication perturbation, recruits DinB onto chromatin to generate the point mutations and single nucleotide frameshifts in the replication mutator. This chain of events reveals a novel checkpoint-induced tolerance mechanism that allows cells to cope with replication perturbation, presumably to make possible restarting stalled replication forks. Fission yeast Cds1 kinase plays an essential role in maintaining DNA replication fork stability in the face of DNA damage and replication fork stalling. Cds1 kinase is known to regulate three proteins that are implicated in maintaining replication fork stability: Mus81-Eme1, a hetero-dimeric structure-specific endonuclease complex; Rqh1, a RecQ-family helicase involved in suppressing inappropriate recombination during replication; and Rad60, a protein required for recombinational repair during replication. These Cds1-regulated proteins are thought to cooperatively prevent mutagenesis and maintain replication fork stability in cells under replication stress. These checkpoint-regulated processes allow cells to survive replication perturbation by preventing stalled replication forks from degenerating into deleterious DNA structures resulting in genomic instability and cancer development

  15. Berkeley lab checkpoint/restart (BLCR) for Linux clusters

    International Nuclear Information System (INIS)

    Hargrove, Paul H; Duell, Jason C

    2006-01-01

    This article describes the motivation, design and implementation of Berkeley Lab Checkpoint/Restart (BLCR), a system-level checkpoint/restart implementation for Linux clusters that targets the space of typical High Performance Computing applications, including MPI. Application-level solutions, including both checkpointing and fault-tolerant algorithms, are recognized as more time and space efficient than system-level checkpoints, which cannot make use of any application-specific knowledge. However, system-level checkpointing allows for preemption, making it suitable for responding to ''fault precursors'' (for instance, elevated error rates from ECC memory or network CRCs, or elevated temperature from sensors). Preemption can also increase the efficiency of batch scheduling; for instance reducing idle cycles (by allowing for shutdown without any queue draining period or reallocation of resources to eliminate idle nodes when better fitting jobs are queued), and reducing the average queued time (by limiting large jobs to running during off-peak hours, without the need to limit the length of such jobs). Each of these potential uses makes BLCR a valuable tool for efficient resource management in Linux clusters

  16. Comprehensive Immigration Reform: Becoming Americans - U.S. Immigrant Integration

    OpenAIRE

    Rumbaut, RG

    2007-01-01

    Hearing on 'Comprehensive Immigration Reform: Becoming Americans - US Immigrant Integration,' Subcommittee on Immigration, Citizenship, Refugees, Border Security, and International Law of the Committee on the Judiciary, House of Representatives, Serial No. 110-27. May 16, 2007. Abstract: In this statement to a House Hearing on comprehensive immigration reform focusing on immigrant integration, English and foreign language competencies, preferences and use among immigrants and thei...

  17. Immigrant entrepreneurship in Norway

    OpenAIRE

    Vinogradov, Evgueni

    2008-01-01

    Doctoral thesis (Ph.D.) – Bodø Graduate School of Business, 2008 The purpose of this doctoral thesis is to add to the knowledge about immigrant entrepreneurship in Norway and to test the existing theories relating to immigrant entrepreneurship. In this work, an immigrant entrepreneur is defined as a business owner born outside Norway with both parents born abroad who is involved into the activities characterised by economic innovation, organisation creation, and profit-seeking in the marke...

  18. Prejudice and Immigration

    OpenAIRE

    Paolo E Giordani; Michele Ruta

    2008-01-01

    We study immigration policy in a small open receiving economy under self-selection of migrants. We show that immigration policy choice affects and is affected by the migratory decisions of skilled and unskilled foreign workers. From this interaction multiple equilibria may arise, which are driven by the natives' expectations on the migrants' size and skill composition (and, hence, on the welfare effects of immigration). In particular, pessimistic (optimistic) beliefs induce a country to impos...

  19. Developmental checkpoints and feedback circuits time insect maturation

    DEFF Research Database (Denmark)

    Rewitz, Kim Furbo; Yamanaka, Naoki; O'Connor, Michael B.

    2013-01-01

    as external cues, to time production and release of ecdysone. Based on results discussed here, we suggest that developmental progression to adulthood is controlled by checkpoints that regulate the genetic timing program enabling it to adapt to different environmental conditions. These checkpoints utilize...... a number of signaling pathways to modulate ecdysone production in the prothoracic gland. Release of ecdysone activates an autonomous cascade of both feedforward and feedback signals that determine the duration of the ecdysone pulse at each developmental transitions. Conservation of the genetic mechanisms...... that coordinate the juvenile-adult transition suggests that insights from the fruit fly Drosophila will provide a framework for future investigation of developmental timing in metazoans....

  20. The Dynamical Mechanisms of the Cell Cycle Size Checkpoint

    International Nuclear Information System (INIS)

    Feng Shi-Fu; Yang Ling; Yan Jie; Liu Zeng-Rong

    2012-01-01

    Cell division must be tightly coupled to cell growth in order to maintain cell size, whereas the mechanisms of how initialization of mitosis is regulated by cell size remain to be elucidated. We develop a mathematical model of the cell cycle, which incorporates cell growth to investigate the dynamical properties of the size checkpoint in embryos of Xenopus laevis. We show that the size checkpoint is naturally raised from a saddle-node bifurcation, and in a mutant case, the cell loses its size control ability due to the loss of this saddle-node point

  1. ATM and checkpoint responses to DNA double strand breaks

    International Nuclear Information System (INIS)

    Khanna, K.K.

    2003-01-01

    DNA damage checkpoints can be classified into G1/S, intra-S and G2/M checkpoints, so named according to the cell cycle transitions that they regulate. DNA damage incurred during the G1 or G2 phase of the cell cycle leads to growth arrest at the G1/S and G2/M phase boundaries, respectively, whereas genotoxic stress during S phase results in the transient suppression of DNA synthesis. In mammals, ATM (ataxia-telangiectasia mutated) is a protein kinase that controls all checkpoint responses to DNA damage. ATM is a versatile kinase which uses various means to regulate a given checkpoint pathway. It has been shown to act upon several proteins within the same pathway, many times controlling several different modifications of the same protein or using several different targets to arrive at the same end point. Some of the ATM targets act as adaptors by recruiting additional substrates for ATM. ATM controls two types of responses in G1. The p53-dependent responses inhibit Cyclin/Cdk activity by transcriptional induction of p21, whereas p53-independent responses inhibit CDKs through degradation of Cdc25A to maintain CdK2 inhibitory phosphorylation. In regulating p53, ATM directly phosphorylates p53 on Ser15, which likely causes p53 transcriptional activation, concurrently activating other kinases that phosphorylate p53 at other sites such as Ser20, which reduces the ability of MDM2 to bind p53, thus promoting its stability. ATM further ensures p53 stability by phosphorylating MDM2. At least six ATM targets, namely CHK2, CHK1, NBS1, BRCA1, SMC1 and FANCD2, have been implicated in the control of S-phase checkpoint. Cdc25A is the downstream effector of CHK1 and CHK2, though the underlying mechanism for control of intra S-phase checkpoint by other targets remain obscure. G2 checkpoint prevents mitotic entry solely through inhibitory phosphorylation of Cdc2/Cdk1. Several ATM targets including CHK1, CHK2, BRCA1, MDC1 and p53BP1 have been implicated in the control of G2/M

  2. The integration of immigrants

    OpenAIRE

    Bauböck, Rainer

    1995-01-01

    from the Table of Contents: Migration and integration - Basic concepts and definitions; Immigration and Integration policies; The legal framework for integration; Dimension of social integration; Cultural integration; Conclusions;

  3. The DNA Replication Checkpoint Directly Regulates MBF-Dependent G1/S Transcription▿

    OpenAIRE

    Dutta, Chaitali; Patel, Prasanta K.; Rosebrock, Adam; Oliva, Anna; Leatherwood, Janet; Rhind, Nicholas

    2008-01-01

    The DNA replication checkpoint transcriptionally upregulates genes that allow cells to adapt to and survive replication stress. Our results show that, in the fission yeast Schizosaccharomyces pombe, the replication checkpoint regulates the entire G1/S transcriptional program by directly regulating MBF, the G1/S transcription factor. Instead of initiating a checkpoint-specific transcriptional program, the replication checkpoint targets MBF to maintain the normal G1/S transcriptional program du...

  4. Cell cycle checkpoints: reversible when possible, irreversible when needed

    NARCIS (Netherlands)

    Krenning, L.

    2015-01-01

    Cell cycle checkpoints are reversible in nature, and can prevent progression into the next cell cycle phase if needed. In the case of DNA damage, cells can prevent progression from G1 into S phase, and from G2 into mitosis in the presence of DNA double strand breaks. Following DNA repair, these

  5. Development of cell-cycle checkpoint therapy for solid tumors.

    Science.gov (United States)

    Tamura, Kenji

    2015-12-01

    Cellular proliferation is tightly controlled by several cell-cycle checkpoint proteins. In cancer, the genes encoding these proteins are often disrupted and cause unrestrained cancer growth. The proteins are over-expressed in many malignancies; thus, they are potential targets for anti-cancer therapies. These proteins include cyclin-dependent kinase, checkpoint kinase, WEE1 kinase, aurora kinase and polo-like kinase. Cyclin-dependent kinase inhibitors are the most advanced cell-cycle checkpoint therapeutics available. For instance, palbociclib (PD0332991) is a first-in-class, oral, highly selective inhibitor of CDK4/6 and, in combination with letrozole (Phase II; PALOMA-1) or with fulvestrant (Phase III; PALOMA-3), it has significantly prolonged progression-free survival, in patients with metastatic estrogen receptor-positive, HER2-negative breast cancer, in comparison with that observed in patients using letrozole, or fulvestrant alone, respectively. In this review, we provide an overview of the current compounds available for cell-cycle checkpoint protein-directed therapy for solid tumors. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  6. Immune-Checkpoint Blockade and Active Immunotherapy for Glioma

    Energy Technology Data Exchange (ETDEWEB)

    Ahn, Brian J. [Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213 (United States); Brain Tumor Program, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213 (United States); Pollack, Ian F. [Brain Tumor Program, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213 (United States); Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213 (United States); Okada, Hideho, E-mail: okadah@upmc.edu [Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213 (United States); Brain Tumor Program, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213 (United States); Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213 (United States); Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213 (United States)

    2013-11-01

    Cancer immunotherapy has made tremendous progress, including promising results in patients with malignant gliomas. Nonetheless, the immunological microenvironment of the brain and tumors arising therein is still believed to be suboptimal for sufficient antitumor immune responses for a variety of reasons, including the operation of “immune-checkpoint” mechanisms. While these mechanisms prevent autoimmunity in physiological conditions, malignant tumors, including brain tumors, actively employ these mechanisms to evade from immunological attacks. Development of agents designed to unblock these checkpoint steps is currently one of the most active areas of cancer research. In this review, we summarize recent progresses in the field of brain tumor immunology with particular foci in the area of immune-checkpoint mechanisms and development of active immunotherapy strategies. In the last decade, a number of specific monoclonal antibodies designed to block immune-checkpoint mechanisms have been developed and show efficacy in other cancers, such as melanoma. On the other hand, active immunotherapy approaches, such as vaccines, have shown encouraging outcomes. We believe that development of effective immunotherapy approaches should ultimately integrate those checkpoint-blockade agents to enhance the efficacy of therapeutic approaches. With these agents available, it is going to be quite an exciting time in the field. The eventual success of immunotherapies for brain tumors will be dependent upon not only an in-depth understanding of immunology behind the brain and brain tumors, but also collaboration and teamwork for the development of novel trials that address multiple layers of immunological challenges in gliomas.

  7. Immune checkpoint inhibitors for nonsmall cell lung cancer treatment

    Directory of Open Access Journals (Sweden)

    Yuh-Min Chen

    2017-01-01

    Full Text Available Immune checkpoint inhibition with blocking antibodies that target cytotoxic T-lymphocyte antigen-4 (CTLA-4 and the programmed cell death protein 1 (PD-1 pathway [PD-1/programmed death-ligand 1 (PD-L1] have demonstrated promise in a variety of malignancies. While ipilimumab has been approved as a CTLA-4 blocking antibody by the US Food and Drug Administration for the treatment of advanced melanoma, it is still not approved for lung cancer treatment. In contrast, nivolumab and pembrolizumab, both PD-1 blocking antibodies, have been approved for second-line treatment of nonsmall cell lung cancer in 2015 because of their high potency and long-lasting effects in some patient subgroups. Other PD-1 and PD-L1 monoclonal antibodies are also in active development phase. Treatment with such immune checkpoint inhibitors is associated with a unique pattern of immune-related adverse events or side effects. Combination approaches involving CTLA-4 and PD-1/PD-L1 blockade or checkpoint inhibitors with chemotherapy or radiotherapy are being investigated to determine whether they may enhance the efficacy of treatment. Despite many challenges ahead, immunotherapy with checkpoint inhibitors has already become a new and important treatment modality for lung cancer in the last decade following the discovery of targeted therapy.

  8. Immune-Checkpoint Blockade and Active Immunotherapy for Glioma

    International Nuclear Information System (INIS)

    Ahn, Brian J.; Pollack, Ian F.; Okada, Hideho

    2013-01-01

    Cancer immunotherapy has made tremendous progress, including promising results in patients with malignant gliomas. Nonetheless, the immunological microenvironment of the brain and tumors arising therein is still believed to be suboptimal for sufficient antitumor immune responses for a variety of reasons, including the operation of “immune-checkpoint” mechanisms. While these mechanisms prevent autoimmunity in physiological conditions, malignant tumors, including brain tumors, actively employ these mechanisms to evade from immunological attacks. Development of agents designed to unblock these checkpoint steps is currently one of the most active areas of cancer research. In this review, we summarize recent progresses in the field of brain tumor immunology with particular foci in the area of immune-checkpoint mechanisms and development of active immunotherapy strategies. In the last decade, a number of specific monoclonal antibodies designed to block immune-checkpoint mechanisms have been developed and show efficacy in other cancers, such as melanoma. On the other hand, active immunotherapy approaches, such as vaccines, have shown encouraging outcomes. We believe that development of effective immunotherapy approaches should ultimately integrate those checkpoint-blockade agents to enhance the efficacy of therapeutic approaches. With these agents available, it is going to be quite an exciting time in the field. The eventual success of immunotherapies for brain tumors will be dependent upon not only an in-depth understanding of immunology behind the brain and brain tumors, but also collaboration and teamwork for the development of novel trials that address multiple layers of immunological challenges in gliomas

  9. A checkpoint compression study for high-performance computing systems

    Energy Technology Data Exchange (ETDEWEB)

    Ibtesham, Dewan [Univ. of New Mexico, Albuquerque, NM (United States). Dept. of Computer Science; Ferreira, Kurt B. [Sandia National Laboratories (SNL-NM), Albuquerque, NM (United States). Scalable System Software Dept.; Arnold, Dorian [Univ. of New Mexico, Albuquerque, NM (United States). Dept. of Computer Science

    2015-02-17

    As high-performance computing systems continue to increase in size and complexity, higher failure rates and increased overheads for checkpoint/restart (CR) protocols have raised concerns about the practical viability of CR protocols for future systems. Previously, compression has proven to be a viable approach for reducing checkpoint data volumes and, thereby, reducing CR protocol overhead leading to improved application performance. In this article, we further explore compression-based CR optimization by exploring its baseline performance and scaling properties, evaluating whether improved compression algorithms might lead to even better application performance and comparing checkpoint compression against and alongside other software- and hardware-based optimizations. Our results highlights are: (1) compression is a very viable CR optimization; (2) generic, text-based compression algorithms appear to perform near optimally for checkpoint data compression and faster compression algorithms will not lead to better application performance; (3) compression-based optimizations fare well against and alongside other software-based optimizations; and (4) while hardware-based optimizations outperform software-based ones, they are not as cost effective.

  10. CHECKPOINT INHIBITOR IMMUNE THERAPY: Systemic Indications and Ophthalmic Side Effects.

    Science.gov (United States)

    Dalvin, Lauren A; Shields, Carol L; Orloff, Marlana; Sato, Takami; Shields, Jerry A

    2018-06-01

    To review immune checkpoint inhibitor indications and ophthalmic side effects. A literature review was performed using a PubMed search for publications between 1990 and 2017. Immune checkpoint inhibitors are designed to treat system malignancies by targeting one of three ligands, leading to T-cell activation for attack against malignant cells. These ligands (and targeted drug) include cytotoxic T-lymphocyte antigen-4 (CTLA-4, ipilimumab), programmed death protein 1 (PD-1, pembrolizumab, nivolumab), and programmed death ligand-1 (PD-L1, atezolizumab, avelumab, durvalumab). These medications upregulate the immune system and cause autoimmune-like side effects. Ophthalmic side effects most frequently manifest as uveitis (1%) and dry eye (1-24%). Other side effects include myasthenia gravis (n = 19 reports), inflammatory orbitopathy (n = 11), keratitis (n = 3), cranial nerve palsy (n = 3), optic neuropathy (n = 2), serous retinal detachment (n = 2), extraocular muscle myopathy (n = 1), atypical chorioretinal lesions (n = 1), immune retinopathy (n = 1), and neuroretinitis (n = 1). Most inflammatory side effects are managed with topical or periocular corticosteroids, but advanced cases require systemic corticosteroids and cessation of checkpoint inhibitor therapy. Checkpoint inhibitors enhance the immune system by releasing inhibition on T cells, with risk of autoimmune-like side effects. Ophthalmologists should include immune-related adverse events in their differential when examining cancer patients with new ocular symptoms.

  11. Immigration: Coming to America

    Science.gov (United States)

    Anderson, Kristin

    2011-01-01

    To say that immigration is currently a controversial issue would be an understatement. The media is rife with misinformation and does a very poor job of making the critical distinction between legal and illegal immigration. Because of this, it is vitally important that libraries provide students with clear and unbiased material on the topic. In…

  12. Workplace Concentration of Immigrants

    Science.gov (United States)

    Andersson, Fredrik; García-Pérez, Mónica; Haltiwanger, John; McCue, Kristin; Sanders, Seth

    2014-01-01

    Casual observation suggests that in most U.S. urban labor markets, immigrants have more immigrant coworkers than native-born workers do. While seeming obvious, this excess tendency to work together has not been precisely measured, nor have its sources been quantified. Using matched employer–employee data from the U.S. Census Bureau Longitudinal Employer-Household Dynamics (LEHD) database on a set of metropolitan statistical areas (MSAs) with substantial immigrant populations, we find that, on average, 37% of an immigrant’s coworkers are themselves immigrants; in contrast, only 14% of a native-born worker’s coworkers are immigrants. We decompose this difference into the probability of working with compatriots versus with immigrants from other source countries. Using human capital, employer, and location characteristics, we narrow the mechanisms that might explain immigrant concentration. We find that industry, language, and residential segregation collectively explain almost all the excess tendency to work with immigrants from other source countries, but they have limited power to explain work with compatriots. This large unexplained compatriot component suggests an important role for unmeasured country-specific factors, such as social networks. PMID:25425452

  13. Checkpointing for graceful degradation in distributed embedded systems

    Science.gov (United States)

    Sababha, Belal Hussein

    Graceful degradation is an approach to developing dependable safety-critical embedded applications, where redundant active or standby resources are used to cope with faults through a system reconfiguration at run-time. Compared to traditional hardware and software redundancy, it is a promising technique that may achieve dependability with a significant reduction in cost, size, weight, and power requirements. Reconfiguration at run-time necessitates using proper checkpointing protocols to support state reservation to ensure correct task restarts after a system reconfiguration. One of the most common checkpointing protocols are communication induced checkpointing (CIC) protocols, which are well developed and understood for large parallel and information systems, but not much has been done for resource limited embedded systems. This work implements and evaluates some of the most common CIC protocols in a periodic resource constrained distributed embedded system for graceful degradation purposes. A test-bed has been developed and used for the evaluation of the various protocols. The implemented protocols are thoroughly studied and performances are contrasted. Specifically the periodicity property and how it benefits checkpointing in embedded systems is investigated. This work introduces a unique effort of CIC protocol implementation and evaluation in the field of distributed embedded systems. Other than providing a test-bed for graceful degradation support, this work shows that some checkpointing protocols that are not efficient in large information systems and supercomputers perform well in embedded systems. We show that a simple index-based CIC protocol, such as the BCS protocol, is more appropriate in embedded system applications compared to other protocols that piggyback a significant amount of information to reduce the number of forced checkpoints. Finally, this work proposes a whole graceful degradation approach to achieve fault tolerance in resource constrained

  14. On the move: Analyzing immigration determinants and immigrant outcomes

    NARCIS (Netherlands)

    Falcke, S.|info:eu-repo/dai/nl/372640060

    2017-01-01

    Given the increased number of immigrants worldwide, the determinants of immigration and the social and economic integration of immigrants into the countries of destination are of particular importance. The contributions of this dissertation address the determinants of immigration by looking at the

  15. Age at Immigration and Educational Attainment of Young Immigrants

    NARCIS (Netherlands)

    van Ours, J.C.; Veenman, J.M.C.

    2005-01-01

    For immigrants who arrive in a country at a young age it is easier to assimilate than for teenagers.This paper investigates up to what immigration age the educational attainment of young immigrants in the Netherlands is similar to the educational attainment of secondgeneration immigrants, who were

  16. Attitudes towards Immigration

    DEFF Research Database (Denmark)

    Dinesen, Peter Thisted; Klemmensen, Robert; Nørgaard, Asbjørn Sonne

    2016-01-01

    This article examines if deep-seated psychological differences add to the explanation of attitudes toward immigration. We explore whether the Big Five personality traits matter for immigration attitudes beyond the traditional situational factors of economic and cultural threat and analyze how...... individuals with different personalities react when confronted with the same situational triggers. Using a Danish survey experiment, we show that different personality traits have different effects on opposition toward immigration. We find that Openness has an unconditional effect on attitudes toward...... high on Conscientiousness are more sensitive to the skill level of immigrants. The results imply that personality is important for attitudes toward immigration, and in the conclusion, we further discuss how the observed conditional and unconditional effects of personality make sense theoretically....

  17. Holdninger til Immigration

    DEFF Research Database (Denmark)

    Malchow-Møller, Nikolaj; Roland Munch, Jakob; Schroll, Sanne

    2006-01-01

    Denne artikel belyser holdninger til immigration blandt borgere i Danmark og de øvrige EU-15 lande - herunder holdningerne til immigration, der følger af den seneste EU-udvidelse. Det analyseres, hvilke faktorer der ligger til frund for disse holdninger, samt i hvilken udstrækning danskere afviger...... fra EU-gennemsnittet. Den typiske dansker er lidt mere skeptisk overfor immigration end andre europæere. Danskerne afskiller sig desuden ved, at forholdsvis få forbinder øget immigration med negative konsekvenser for arbejdsmarkedet, men forholdsvis mange forbinder det med højere omkostninger...... for velfærdsstaten. Når der tages hensyn til opfattelserne af de økonomiske konsekvenser af immigration, kommer Danmark til at fremstå som et væsentligt mere immigrationsskeptisk land, end hvad der kommer til udtryk i de ukorrigerede holdninger....

  18. Holdninger til immigration

    DEFF Research Database (Denmark)

    Malchow-Møller, Nikolaj; Munch, Jakob Roland; Schroll, Sanne

    Denne artikel belyser holdninger til immigration blandt borgere i Danmark og de øvrige EU-15 lande - herunder holdningerne til immigration, der følger af den seneste EU-udvidelse. Det analyseres, hvilke faktorer der ligger til frund for disse holdninger, samt i hvilken udstrækning danskere afviger...... fra EU-gennemsnittet. Den typiske dansker er lidt mere skeptisk overfor immigration end andre europæere. Danskerne afskiller sig desuden ved, at forholdsvis få forbinder øget immigration med negative konsekvenser for arbejdsmarkedet, men forholdsvis mange forbinder det med højere omkostninger...... for velfærdsstaten. Når der tages hensyn til opfattelserne af de økonomiske konsekvenser af immigration, kommer Danmark til at fremstå som et væsentligt mere immigrationsskeptisk land, end hvad der kommer til udtryk i de ukorrigerede holdninger...

  19. Checkpoint inhibitors in endometrial cancer: preclinical rationale and clinical activity.

    Science.gov (United States)

    Mittica, Gloria; Ghisoni, Eleonora; Giannone, Gaia; Aglietta, Massimo; Genta, Sofia; Valabrega, Giorgio

    2017-10-27

    Treatment of advanced and recurrent endometrial cancer (EC) is still an unmet need for oncologists and gynecologic oncologists. The Cancer Genome Atlas Research Network (TCGA) recently provided a new genomic classification, dividing EC in four subgroups. Two types of EC, the polymerase epsilon (POLE)-ultra-mutated and the microsatellite instability-hyper-mutated (MSI-H), are characterized by a high mutation rate providing the rationale for a potential activity of checkpoint inhibitors. We analyzed all available evidence supporting the role of tumor microenvironment (TME) in EC development and the therapeutic implications offered by immune checkpoint inhibitors in this setting. We performed a review on Pubmed with Mesh keywords 'endometrial cancer' and the name of each checkpoint inhibitor discussed in the article. The same search was operated on clinicaltrial.gov to identify ongoing clinical trials exploring PD-1/PD-L1 and CTLA-4 axis in EC, particularly focusing on POLE-ultra-muted and MSI-H cancer types. POLE-ultra-mutated and MSI-H ECs showed an active TME expressing high number of neo-antigens and an elevated amount of tumor infiltrating lymphocytes (TILs). Preliminary results from a phase-1 clinical trial (KEYNOTE-028) demonstrated antitumor activity of Pembrolizumab in EC. Moreover, both Pembrolizumab and Nivolumab reported durable clinical responses in POLE-ultra-mutated patients. Immune checkpoint inhibitors are an attractive option in POLE-ultra-mutated and MSI-H ECs. Future investigations in these subgroups include combinations of checkpoints inhibitors with chemotherapy and small tyrosine kinase inhibitors (TKIs) to enhance a more robust intra-tumoral immune response.

  20. Cell size checkpoint control by the retinoblastoma tumor suppressor pathway.

    Science.gov (United States)

    Fang, Su-Chiung; de los Reyes, Chris; Umen, James G

    2006-10-13

    Size control is essential for all proliferating cells, and is thought to be regulated by checkpoints that couple cell size to cell cycle progression. The aberrant cell-size phenotypes caused by mutations in the retinoblastoma (RB) tumor suppressor pathway are consistent with a role in size checkpoint control, but indirect effects on size caused by altered cell cycle kinetics are difficult to rule out. The multiple fission cell cycle of the unicellular alga Chlamydomonas reinhardtii uncouples growth from division, allowing direct assessment of the relationship between size phenotypes and checkpoint function. Mutations in the C. reinhardtii RB homolog encoded by MAT3 cause supernumerous cell divisions and small cells, suggesting a role for MAT3 in size control. We identified suppressors of an mat3 null allele that had recessive mutations in DP1 or dominant mutations in E2F1, loci encoding homologs of a heterodimeric transcription factor that is targeted by RB-related proteins. Significantly, we determined that the dp1 and e2f1 phenotypes were caused by defects in size checkpoint control and were not due to a lengthened cell cycle. Despite their cell division defects, mat3, dp1, and e2f1 mutants showed almost no changes in periodic transcription of genes induced during S phase and mitosis, many of which are conserved targets of the RB pathway. Conversely, we found that regulation of cell size was unaffected when S phase and mitotic transcription were inhibited. Our data provide direct evidence that the RB pathway mediates cell size checkpoint control and suggest that such control is not directly coupled to the magnitude of periodic cell cycle transcription.

  1. [French immigration policy].

    Science.gov (United States)

    Weil, P

    1994-01-01

    From the late nineteenth century through 1974, France permitted immigration to furnish workers and to compensate for the low level of fertility. Intense immigration from North Africa, the economic crisis of the 1970s, and other factors led to policy changes in 1974. French immigration policy since 1974 has fluctuated between guaranteeing foreigners equal rights regardless of their religion, race, culture, or national origin, and attempting to differentiate among immigrants depending on their degree of assimilability to French culture. From 1974 to 1988, France had five different policies regarding whether to permit new immigration and what to do about illegal immigrants. In July 1984, the four major political parties unanimously supported a measure in Parliament that definitively guaranteed the stay in France of legal immigrants, whose assimilation thus assumed priority. Aid for return to the homeland was no longer to be widely offered, and immigration of unskilled workers was to be terminated except for those originating in European Community countries. Major changes of government in 1988 and 1993 affected only the modalities of applying these principles. The number of immigrants has fluctuated since 1974. Unskilled workers, the only category whose entrance was specifically controlled by the 1984 measures, have declined from 174,000 in 1970 to 25,000 in the early 1990s. The number of requests for political asylum declined from 60,000 in 1989 to 27,000 in 1993, and in 1991, 15,467 persons were granted refugee status. The number of immigrants of all types permitted to remain in France declined from 250,000 or 3000 per year in the early 1970s to around 110,000 at present. Although the decline is significant, it appears insufficient to the government in power since 1993. Although migratory flows are often explained as the product of imbalance in the labor market or in demographic growth, the French experience suggests that government policies, both in the sending and

  2. Voting over Selective Immigration Policies with Immigration Aversion

    OpenAIRE

    Giuseppe Russo

    2011-01-01

    The claim that "skilled immigration is welcome" is often associated to the increasing adoption of selective immigration policies. I study the voting over differentiated immigration policies in a two-country, three-factor general equilibrium model where there exist skilled and unskilled workers, migration decisions are endogenous, enforcing immigration restriction is costly, and natives dislike unskilled immigration. According to my findings, decisions over border closure are made to protect t...

  3. The Human Face of Immigration

    Science.gov (United States)

    Costello, Maureen

    2011-01-01

    In the past, nativists opposed immigration, period. The sharp distinction between "legal" and "illegal" immigrants emerged fairly recently, according to immigration historian David Reimers, a professor of history at New York University. "Basically, by the mid-90s 'legal' immigration was no longer an issue," he says.…

  4. Empower Educators to Teach Immigration

    Science.gov (United States)

    Burnett, Sara; Kugler, Eileen Gale; Tesh, Claire

    2016-01-01

    Over the past decades, U.S. immigration has changed significantly, yet the way we teach about immigration in schools has changed little. The American Immigration Council has developed a two-year program on Long Island, an area experiencing an increase of new arrivals and anti-immigrant sentiment. The program empowers teachers with the knowledge to…

  5. Latino Immigration, Education, and Opportunity

    Science.gov (United States)

    Jimenez, Rosa M.

    2012-01-01

    Immigration is often framed as a problem, yet it is also a time of remarkable opportunity. While immigrants come to the United States from all over the world, the author focuses on the unique and urgent issues related to Latino immigration. Immigrant Latinos have changed the face of America and U.S. schools. Approximately one in five K-12 students…

  6. Overeducation among immigrants in Sweden

    DEFF Research Database (Denmark)

    Andersson Joona, Pernilla; Datta Gupta, Nabanita; Wadensjo, Eskil

    2014-01-01

    The utilization and reward of the human capital of immigrants in the labor market of the host country has been studied extensively. Using Swedish register data from 2001–2008, we extend the immigrant educational mismatch literature by analyzing incidence, wage effects and state dependence...... in overeducation among natives and immigrants. In line with previous research we find a higher incidence and a lower return to overeducation among immigrants indicating that immigrants lose more from being overeducated. We find a high degree of state dependence in overeducation both among natives and immigrants......, but considerably higher among immigrants....

  7. Immigration And Self-Selection

    OpenAIRE

    George J. Borjas

    1988-01-01

    Self-selection plays a dominant role in determining the size and composition of immigrant flows. The United States competes with other potential host countries in the "immigration market". Host countries vary in their "offers" of economic opportunities and also differ in the way they ration entry through their immigration policies. Potential immigrants compare the various opportunities and are non-randomly sorted by the immigration market among the various host countries. This paper presents ...

  8. Toward immigration reform.

    Science.gov (United States)

    Franken, Mark

    2005-01-01

    For the most part, immigrants in the United States do not have access to the very safety-net benefits supported by their taxes, nor to essential due-process rights, simply because they are not citizens or legal residents. Contemporary demographics of immigration and post-9/11 security concerns have colored our traditional hospitality as a nation of immigrants and made life more difficult for immigrants. The Catholic Church has a rich history of scriptural and social teaching that addresses the question of immigration. Stories of forced migration in the Pentateuch led to commandments regarding strangers and the responsibility to be welcoming. In the New Testament, we see that the Holy Family themselves were refugees. The Gospel of St. Matthew tells us that we will be judged by the way we respond to migrants and others in need. In Exsul Familia, Pope Pius XII reaffirms the commitment of the church to care for pilgrims, aliens, exiles, and migrants. In Ecclesia in America, Pope John Paul II states that the ultimate solution to illegal immigration is the elimination of global underdevelopment and that, in the meantime, the human rights of all migrants must be respected. In 2003, the bishops of Mexico and the United States jointly issued the pastoral letter Strangers No Longer: Together on the Journey of Hope. In this letter, the bishops say that U.S. immigration policy should protect the human rights and dignity of immigrants and asylum seekers. The bishops also offer a number of proposed public policy responses toward that end. To advance the principles contained in Strangers No Longer, the bishops have decided to mount a national campaign designed to unite and mobilize a growing network of Catholic organizations and individuals, as well as others of good faith. In addition, the campaign will seek to dispel myths and misperceptions about immigrants.

  9. "A Day Without Immigrants"

    DEFF Research Database (Denmark)

    Heiskanen, Benita

    2009-01-01

    Abstract This article considers the debates surrounding the "Day Without Immigrants" protests organized in major U.S. cities on 1 May 2006, prompted by H.R. 4437, the Border Protection, Anti-Terrorism, and Illegal Immigration Control Act of 2005, from the multiple perspectives of scholars, pundits...... that the rhetoric used in these discourses pitted various class-based ethnoracial groups against each other not so much to tackle the proposed immigration bill but, rather, to comment on the ramifications of an increasingly multiracial United States. Udgivelsesdato: 01 December 2009...

  10. Immigration and income inequality

    DEFF Research Database (Denmark)

    Deding, Mette; Jakobsen, Vibeke; Azhar, Hussain

    Four income inequality measures (Gini-coefficient, 90/10-decile ratio, and two generalized entropy indices) are applied to analyse immigrants’ income position relative to natives in a comparative perspective. Administrative data is used for Denmark, while survey data is used for Germany. We find...... higher inequality among immigrants than natives in Denmark, but vice versa for Germany. Over the period 1984-2003, this inequality gap has narrowed in both countries. At the same time, the contribution of immigrants to overall inequality has increased systematically, primarily caused by the increased...... share of immigrants in the population....

  11. Obesity and Regional Immigrant Density.

    Science.gov (United States)

    Emerson, Scott D; Carbert, Nicole S

    2017-11-24

    Canada has an increasingly large immigrant population. Areas of higher immigrant density, may relate to immigrants' health through reduced acculturation to Western foods, greater access to cultural foods, and/or promotion of salubrious values/practices. It is unclear, however, whether an association exists between Canada-wide regional immigrant density and obesity among immigrants. Thus, we examined whether regional immigrant density was related to obesity, among immigrants. Adult immigrant respondents (n = 15,595) to a national population-level health survey were merged with region-level immigrant density data. Multi-level logistic regression was used to model the odds of obesity associated with increased immigrant density. The prevalence of obesity among the analytic sample was 16%. Increasing regional immigrant density was associated with lower odds of obesity among minority immigrants and long-term white immigrants. Immigrant density at the region-level in Canada may be an important contextual factor to consider when examining obesity among immigrants.

  12. Helping Immigrants Become Teachers.

    Science.gov (United States)

    Ross, Flynn

    2001-01-01

    Describes Newcomers Entering Teaching, a program designed by the Portland (Maine) Public Schools to prepare recent immigrants and refugees to enter local university's 9-month teacher-certification program. (PKP)

  13. Liberal nationalism on immigration

    DEFF Research Database (Denmark)

    Lægaard, Sune

    2009-01-01

    Liberal nationalists such as David Miller and Will Kymlicka have claimed that liberal principles have implausible implications with regard to the issue of immigration. They hold that nationality should play a normative role in this regard, and that this is necessary in order to justify restrictions...... on immigration. The present chapter discusses the envisaged role for considerations of nationality with regard to admission and residence, and examines the actual implications of arguments advanced by liberal nationalists as to why nationality should play this role. It is argued that the connection between...... nationality and immigration on liberal nationalist premises is not as straightforward as one might expect, and that the addition of considerations of nationality to liberal principles makes no practical difference with regard to reasons for restricting immigration or criteria of selection among applicants...

  14. Libertarianism and Immigration

    Directory of Open Access Journals (Sweden)

    Diana Virginia Todea

    2010-11-01

    Full Text Available In this paper I investigate the libertarian account of immigration. In the first section I distinguish between right-libertarianism and left-libertarianism. In the second section I analyze the arguments focused on immigration from the perspective of self-ownership focused on Nozick’s case and Steiner’s analogy. In the third section I discuss the conflict between the collective consent on the issue of immigration and the individuals’ decision. The conclusion sets the libertarian framework as being flawed in its argumentation on the issue of immigration because it fails to provide strong arguments about the fact that the individuals are free to choose to open or close the borders.

  15. Immigrants and Native Workers

    DEFF Research Database (Denmark)

    Foged, Mette; Peri, Giovanni

    Using a database that includes the universe of individuals and establishments in Denmark over the period 1991-2008 we analyze the effect of a large inflow of non-European (EU) immigrants on Danish workers. We first identify a sharp and sustained supply-driven increase in the inflow of non......-EU immigrants in Denmark, beginning in 1995 and driven by a sequence of international events such as the Bosnian, Somalian and Iraqi crises. We then look at the response of occupational complexity, job upgrading and downgrading, wage and employment of natives in the short and long run. We find...... that the increased supply of non-EU low skilled immigrants pushed native workers to pursue more complex occupations. This reallocation happened mainly through movement across firms. Immigration increased mobility of natives across firms and across municipalities but it did not increase their probability...

  16. Immigrant Child Poverty

    DEFF Research Database (Denmark)

    Galloway, Taryn Ann; Gustafsson, Björn; Pedersen, Peder J.

    2015-01-01

    Immigrant and native child poverty in Denmark, Norway, and Sweden 1993–2001 is studied using large sets of panel data. While native children face yearly poverty risks of less than 10 percent in all three countries and for all years studied the increasing proportion of immigrant children...... with an origin in middle- and low-income countries have poverty risks that vary from 38 up to as much as 58 percent. At the end of the observation period, one third of the poor children in Norway and as high as about a half in Denmark and in Sweden are of immigrant origin. The strong overrepresentation...... of immigrant children from low- and middle-income countries when measured in yearly data is also found when applying a longer accounting period for poverty measurement. We find that child poverty rates are generally high shortly after arrival to the new country and typically decrease with years since...

  17. Covering Resilience: A Recent Development for Binomial Checkpointing

    Energy Technology Data Exchange (ETDEWEB)

    Walther, Andrea; Narayanan, Sri Hari Krishna

    2016-09-12

    In terms of computing time, adjoint methods offer a very attractive alternative to compute gradient information, required, e.g., for optimization purposes. However, together with this very favorable temporal complexity result comes a memory requirement that is in essence proportional with the operation count of the underlying function, e.g., if algorithmic differentiation is used to provide the adjoints. For this reason, checkpointing approaches in many variants have become popular. This paper analyzes an extension of the so-called binomial approach to cover also possible failures of the computing systems. Such a measure of precaution is of special interest for massive parallel simulations and adjoint calculations where the mean time between failure of the large scale computing system is smaller than the time needed to complete the calculation of the adjoint information. We describe the extensions of standard checkpointing approaches required for such resilience, provide a corresponding implementation and discuss first numerical results.

  18. The Ethics of Immigration

    OpenAIRE

    Matt S. Whitt

    2014-01-01

    Joseph H. Carens. The Ethics of Immigration(Oxford: Oxford University Press, 2013). 384 pages. ISBN 9780199933839. US$35 (Hardback).When philosophers and political theorists turn their attention to migration, they often prioritize general normative commitments, giving only secondary concern to whether these commitments are reflected in policy. As a result, pressing issues affecting the status, rights, and life-chances of immigrants can get lost in abstract debates over the right of states to ...

  19. Implementing forward recovery using checkpointing in distributed systems

    Science.gov (United States)

    Long, Junsheng; Fuchs, W. K.; Abraham, Jacob A.

    1991-01-01

    The paper describes the implementation of a forward recovery scheme using checkpoints and replicated tasks. The implementation is based on the concept of lookahead execution and rollback validation. In the experiment, two tasks are selected for the normal execution and one for rollback validation. It is shown that the recovery strategy has nearly error-free execution time and an average redundancy lower than TMR.

  20. Analysis of Drug Development Paradigms for Immune Checkpoint Inhibitors.

    Science.gov (United States)

    Jardim, Denis L; de Melo Gagliato, Débora; Giles, Francis J; Kurzrock, Razelle

    2018-04-15

    Immune checkpoint inhibitors have unique toxicities and response kinetics compared with cytotoxic and gene-targeted anticancer agents. We investigated the impact of innovative/accelerated immunotherapy drug development/approval models on the accuracy of safety and efficacy assessments by searching the FDA website. Initial phase I trials for each agent were reviewed and safety and efficacy data compared with that found in later trials leading to regulatory approvals of the same agents. As of June 2017, the FDA approved six checkpoint inhibitors for a variety of cancer types. All checkpoint inhibitors received a priority review status and access to at least two additional FDA special access programs, more often breakthrough therapy designation and accelerated approval. Median clinical development time (investigational new drug application to approval) was 60.77 months [avelumab had the shortest timeline (52.33 months)]. Response rates during early phase I trials (median = 16%) are higher than for phase I trials of other agents (with the exception of gene-targeted agents tested with a biomarker). Doses approved were usually not identical to doses recommended on phase I trials. Approximately 50% of types of immune-related and 43% of types of clinically relevant toxicities from later trials were identified in early-phase trials. Even so, treatment-related mortality remains exceedingly low in later studies (0.33% of patients). In conclusion, efficacy and safety of immune checkpoint inhibitors appear to be reasonably predicted from the dose-finding portion of phase I trials, indicating that the fast-track development of these agents is safe and justified. Clin Cancer Res; 24(8); 1785-94. ©2017 AACR . ©2017 American Association for Cancer Research.

  1. Spindle assembly checkpoint acquisition at the mid-blastula transition.

    Directory of Open Access Journals (Sweden)

    Maomao Zhang

    Full Text Available The spindle assembly checkpoint (SAC maintains the fidelity of chromosome segregation during mitosis. Nonpathogenic cells lacking the SAC are typically only found in cleavage stage metazoan embryos, which do not acquire functional checkpoints until the mid-blastula transition (MBT. It is unclear how proper SAC function is acquired at the MBT, though several models exist. First, SAC acquisition could rely on transcriptional activity, which increases dramatically at the MBT. Embryogenesis prior to the MBT relies primarily on maternally loaded transcripts, and if SAC signaling components are not maternally supplied, the SAC would depend on zygotic transcription at the MBT. Second, checkpoint acquisition could depend on the Chk1 kinase, which is activated at the MBT to elongate cell cycles and is required for the SAC in somatic cells. Third, SAC function could depend on a threshold nuclear to cytoplasmic (N:C ratio, which increases during pre-MBT cleavage cycles and dictates several MBT events like zygotic transcription and cell cycle remodeling. Finally, the SAC could by regulated by a timer mechanism that coincides with other MBT events but is independent of them. Using zebrafish embryos we show that SAC acquisition at the MBT is independent of zygotic transcription, indicating that the checkpoint program is maternally supplied. Additionally, by precociously lengthening cleavage cycles with exogenous Chk1 activity, we show that cell cycle lengthening and Chk1 activity are not sufficient for SAC acquisition. Furthermore, we find that SAC acquisition can be uncoupled from the N:C ratio. Together, our findings indicate that SAC acquisition is regulated by a maternally programmed developmental timer.

  2. Italians and Foreign Immigration

    Directory of Open Access Journals (Sweden)

    Corrado Bonifazi

    2006-01-01

    Full Text Available Opinion surveys on attitudes towards immigration are becoming more and more important, owing to the increasing role of political debate on migration issues in Western European countries. CNR has conducted four surveys on this topic, collecting data on the evolution of Italians attitudes towards migration issues. In fact, the ? rst survey was conducted in the second half of the eighties, when foreign immigration was in its early stages. The last survey took place in 2002, when immigration was already well established in Italy. The article focuses on three main issues: the global impact of immigration on Italian society, the immigrants role in the labour market, and immigration policy. In general, the results of the last survey con? rm a trend that appeared already in 1997, of more balanced and realistic opinion that were less of a response to circumstances perceived as special emergencies. Highly educated people, teachers and students continue to be the most open and receptive groups, whereas the less favourably inclined and more worried continue to be old people, those with less education, the unemployed, housewives, and retirees.

  3. The final checkpoint. Cancer as an adaptive evolutionary mechanism

    Directory of Open Access Journals (Sweden)

    Rumena Petkova

    2016-05-01

    Full Text Available The mechanisms for identification of DNA damage and repair usually manage DNA damage very efficiently. If damaged cells manage to bypass the checkpoints where the integrity of the genome is assessed and the decisions whether to proceed with the cell cycle are made, they may evade the imperative to stop dividing and to die. As a result, cancer may develop. Warding off the potential sequence-altering effects of DNA damage during the life of the individual or the existence span of the species is controlled by a set of larger checkpoints acting on a progressively increasing scale, from systematic removal of damaged cells from the proliferative pool by means of repair of DNA damage/programmed cell death through ageing to, finally, cancer. They serve different purposes and act at different levels of the life cycle, safeguarding the integrity of the genetic backup of the individual, the genetic diversity of the population, and, finally, the survival of the species and of life on Earth. In the light of the theory that cancer is the final checkpoint or the nature's manner to prevent complex organisms from living forever at the expense of genetic stagnation, the eventual failure of modern anti-cancer treatments is only to be expected. Nevertheless, the medicine of today and the near future has enough potential to slow down the progression to terminal cancer so that the life expectancy and the quality of life of cancer-affected individuals may be comparable to those of healthy aged individuals.

  4. Labor Market Discrimination: Vietnamese Immigrants

    Directory of Open Access Journals (Sweden)

    Linus Yamane

    2012-01-01

    Full Text Available Vietnamese and East European immigrants face similar obstacles in the U.S. labor market. This provides for an interesting test of racial discrimination in the labor market. Does it make any difference if an immigrant is Asian or White? When Vietnamese immigrants are compared to East European immigrants, Vietnamese men earn 7-9% less than comparable East European men, with more discrimination among the less educated, and in the larger Vietnamese population centers like California. Vietnamese women earn as much as comparable East European women. Vietnamese immigrants, male and female, are much less likely to hold managerial and supervisory positions than comparable East European immigrants.

  5. Labor Market Discrimination: Vietnamese Immigrants

    Directory of Open Access Journals (Sweden)

    Linus Yamane

    2012-01-01

    Full Text Available Vietnamese and East European immigrants face similar obstacles in the US labor market. This provides for an interesting test of racial discrimination in the labor market. Does it make any difference if an immigrant is Asian or White? When Vietnamese immigrants are compared to East European immigrants, Vietnamese men earn 7-9% less than comparable East European men, with more discrimination among the less educated, and in the larger Vietnamese population centers like California. Vietnamese women earn as much as comparable East European women. Vietnamese immigrants, male and female, are much less likely to hold managerial and supervisory positions than comparable East European immigrants.

  6. Sobriety checkpoints in Thailand: a review of effectiveness and developments over time.

    Science.gov (United States)

    Ditsuwan, Vallop; Veerman, J Lennert; Bertram, Melanie; Vos, Theo

    2015-03-01

    This review describes the legal basis for and implementation of sobriety checkpoints in Thailand and identifies factors that influenced their historical development and effectiveness. The first alcohol and traffic injury control law in Thailand was implemented in 1934. The 0.05 g/100 mL blood alcohol concentration limit was set in 1994. Currently, 3 types of sobriety checkpoints are used: general police checkpoints, selective breath testing, and special event sobriety checkpoints. The authors found few reports on the strategies, frequencies, and outcomes for any of these types of checkpoints, despite Thailand having devoted many resources to their implementation. In Thailand and other low-middle income countries, it is necessary to address the country-specific barriers to successful enforcement (including political and logistical issues, lack of equipment, and absence of other supportive alcohol harm reduction measures) before sobriety checkpoints can be expected to be as effective as reported in high-income countries. © 2011 APJPH.

  7. Emodnet Med Sea Check-Point - Indicators for decision- maker

    Science.gov (United States)

    Besnard, Sophie; Claverie, Vincent; Blanc, Frédérique

    2015-04-01

    The Emodnet Checkpoint projects aim is to assess the cost-effectiveness, reliability and utility of the existing monitoring at the sea basin level. This involves the development of monitoring system indicators and a GIS Platform to perform the assessment and make it available. Assessment or production of Check-Point information is made by developing targeted products based on the monitoring data and determining whether the products are meeting the needs of industry and public authorities. Check-point users are the research community, the 'institutional' policy makers for IMP and MSFD implementation, the 'intermediate users', i.e., users capable to understand basic raw data but that benefit from seeing the Checkpoint targeted products and the assessment of the fitness for purpose. We define assessment criteria aimed to characterize/depict the input datasets in terms of 3 territories capable to show performance and gaps of the present monitoring system, appropriateness, availability and fitness for purpose. • Appropriateness: What is made available to users? What motivate/decide them to select this observation rather than this one. • Availability: How this is made available to the user? Place to understand the readiness and service performance of the EU infrastructure • Fitness for use / fitness for purpose: Ability for non-expert user to appreciate the data exploitability (feedback on efficiency & reliability of marine data) For each territory (appropriateness, Availability and Fitness for purpose / for use), we define several indicators. For example, for Availability we define Visibility, Accessibility and Performance. And Visibility is itself defined by "Easily found" and "EU service". So these indicators can be classified according to their territory and sub-territory as seen above, but also according to the complexity to build them. Indicators are built from raw descriptors in 3 stages:  Stage 1: to give a neutral and basic status directly computed from

  8. The spindle assembly checkpoint: More than just keeping track of the spindle.

    OpenAIRE

    Lawrence, KS; Engebrecht, J

    2015-01-01

    Genome stability is essential for cell proliferation and survival. Consequently, genome integrity is monitored by two major checkpoints, the DNA damage response (DDR) and the spindle assembly checkpoint (SAC). The DDR monitors DNA lesions in G1, S, and G2 stages of the cell cycle and the SAC ensures proper chromosome segregation in M phase. There have been extensive studies characterizing the roles of these checkpoints in response to the processes for which they are named; however, emerging e...

  9. The DNA replication checkpoint directly regulates MBF-dependent G1/S transcription.

    Science.gov (United States)

    Dutta, Chaitali; Patel, Prasanta K; Rosebrock, Adam; Oliva, Anna; Leatherwood, Janet; Rhind, Nicholas

    2008-10-01

    The DNA replication checkpoint transcriptionally upregulates genes that allow cells to adapt to and survive replication stress. Our results show that, in the fission yeast Schizosaccharomyces pombe, the replication checkpoint regulates the entire G(1)/S transcriptional program by directly regulating MBF, the G(1)/S transcription factor. Instead of initiating a checkpoint-specific transcriptional program, the replication checkpoint targets MBF to maintain the normal G(1)/S transcriptional program during replication stress. We propose a mechanism for this regulation, based on in vitro phosphorylation of the Cdc10 subunit of MBF by the Cds1 replication-checkpoint kinase. Replacement of two potential phosphorylation sites with phosphomimetic amino acids suffices to promote the checkpoint transcriptional program, suggesting that Cds1 phosphorylation directly regulates MBF-dependent transcription. The conservation of MBF between fission and budding yeast, and recent results implicating MBF as a target of the budding yeast replication checkpoint, suggests that checkpoint regulation of the MBF transcription factor is a conserved strategy for coping with replication stress. Furthermore, the structural and regulatory similarity between MBF and E2F, the metazoan G(1)/S transcription factor, suggests that this checkpoint mechanism may be broadly conserved among eukaryotes.

  10. Action-oriented use of ergonomic checkpoints for healthy work design in different settings.

    Science.gov (United States)

    Kogi, Kazutaka

    2007-12-01

    Recent experiences in the action-oriented use of ergonomic checkpoints in different work settings are reviewed. The purpose is to know what features are useful for healthy work design adjusted to each local situation. Based on the review results, common features of ergonomic checkpoints used in participatory training programs for improving workplace conditions in small enterprises, construction sites, home work and agriculture in industrially developing countries in Asia are discussed. These checkpoints generally compile practical improvement options in a broad range of technical areas, such as materials handling, workstation design, physical environment and work organization. Usually, "action checklists" comprising the tiles of the checkpoints are used together. A clear focus is placed on readily applicable low-cost options. Three common features of these various checkpoints appear to be important. First, the checkpoints represent typical good practices in multiple areas. Second, each how-to section of these checkpoints presents simple improvements reflecting basic ergonomic principles. Examples of these principles include easy reach, fewer and faster transport, elbow-level work, coded displays, isolated or screened hazards and shared teamwork. Third, the illustrated checkpoints accompanied by corresponding checklists are used as group work tools in short-term training courses. Many practical improvements achieved are displayed in websites for inter-country work improvement networks. It is suggested to promote the use of locally adjusted checkpoints in various forms of participatory action-oriented training in small-scale workplaces and in agriculture particularly in industrially developing countries.

  11. The DNA Replication Checkpoint Directly Regulates MBF-Dependent G1/S Transcription▿

    Science.gov (United States)

    Dutta, Chaitali; Patel, Prasanta K.; Rosebrock, Adam; Oliva, Anna; Leatherwood, Janet; Rhind, Nicholas

    2008-01-01

    The DNA replication checkpoint transcriptionally upregulates genes that allow cells to adapt to and survive replication stress. Our results show that, in the fission yeast Schizosaccharomyces pombe, the replication checkpoint regulates the entire G1/S transcriptional program by directly regulating MBF, the G1/S transcription factor. Instead of initiating a checkpoint-specific transcriptional program, the replication checkpoint targets MBF to maintain the normal G1/S transcriptional program during replication stress. We propose a mechanism for this regulation, based on in vitro phosphorylation of the Cdc10 subunit of MBF by the Cds1 replication-checkpoint kinase. Replacement of two potential phosphorylation sites with phosphomimetic amino acids suffices to promote the checkpoint transcriptional program, suggesting that Cds1 phosphorylation directly regulates MBF-dependent transcription. The conservation of MBF between fission and budding yeast, and recent results implicating MBF as a target of the budding yeast replication checkpoint, suggests that checkpoint regulation of the MBF transcription factor is a conserved strategy for coping with replication stress. Furthermore, the structural and regulatory similarity between MBF and E2F, the metazoan G1/S transcription factor, suggests that this checkpoint mechanism may be broadly conserved among eukaryotes. PMID:18662996

  12. Immigration and Swiss House Prices

    OpenAIRE

    Kathrin Degen; Andreas M. Fischer

    2010-01-01

    This study examines the behavior of Swiss house prices to immigration flows for 85 districts from 2001 to 2006. The results show that the nexus between immigration and house prices holds even in an environment of low house price inflation, nationwide rent control, and modest immigration flows. An immigration inflow equal to 1% of an area's population is coincident with an increase in prices for single-family homes of about 2.7%: a result consistent with previous studies. The overall immigrati...

  13. Immigration in American Economic History

    Science.gov (United States)

    Abramitzky, Ran; Boustan, Leah

    2016-01-01

    The United States has long been perceived as a land of opportunity for immigrants. Yet, both in the past and today, US natives have expressed concern that immigrants fail to integrate into US society and lower wages for existing workers. This paper reviews the literatures on historical and contemporary migrant flows, yielding new insights on migrant selection, assimilation of immigrants into US economy and society, and the effect of immigration on the labor market. PMID:29398723

  14. Attitudes Towards Immigration

    DEFF Research Database (Denmark)

    Malchow-Møller, Nikolaj; Munch, Jakob Roland; Schroll, Sanne

    In this paper, we re-examine the role of economic self-interest in shaping people’s attitudes towards immigration, using data from the European Social Survey 2002/2003. Compared to the existing literature, there are two main contributions of the present paper. First, we develop a more powerful test...... of the hypothesis that a positive relationship between education and attitudes towards immigration reflects economic self-interest in the labour market. Second, we develop an alternative and more direct test of whether economic self-interest matters for people’s attitudes towards immigration. We find that while...... the "original" relationship between education and attitudes found in the literature is unlikely to reflect economic self-interest, there is considerable evidence of economic self-interest when using the more direct test...

  15. Attitudes Towards Immigration

    DEFF Research Database (Denmark)

    Malchow-Møller, Nikolaj; Roland Munch, Jakob; Schroll, Sanne

    2006-01-01

    In this paper, we re-examine the role of economic self-interest in shaping people's attitudes towards immigration, using data from the European Social Survey 2002/2003. Compared to the existing literature, there are two main contributions of the present paper. First, we develop a more powerful test...... of the hypothesis that a positive relationship between education and attitudes towards immigration reflects economic self-interest in the labour market. Second, we develop an alternativeand more direct test of whether economic self-interest mattersfor people's attitudes towards immigration. We find that whilethe...... "original" relationship between education and attitudes found in the literature is unlikely to reflect economic self-interest, there is considerable evidence of economic self-interest when using the more directtest....

  16. Multiple Duties for Spindle Assembly Checkpoint Kinases in Meiosis

    Science.gov (United States)

    Marston, Adele L.; Wassmann, Katja

    2017-01-01

    Cell division in mitosis and meiosis is governed by evolutionary highly conserved protein kinases and phosphatases, controlling the timely execution of key events such as nuclear envelope breakdown, spindle assembly, chromosome attachment to the spindle and chromosome segregation, and cell cycle exit. In mitosis, the spindle assembly checkpoint (SAC) controls the proper attachment to and alignment of chromosomes on the spindle. The SAC detects errors and induces a cell cycle arrest in metaphase, preventing chromatid separation. Once all chromosomes are properly attached, the SAC-dependent arrest is relieved and chromatids separate evenly into daughter cells. The signaling cascade leading to checkpoint arrest depends on several protein kinases that are conserved from yeast to man. In meiosis, haploid cells containing new genetic combinations are generated from a diploid cell through two specialized cell divisions. Though apparently less robust, SAC control also exists in meiosis. Recently, it has emerged that SAC kinases have additional roles in executing accurate chromosome segregation during the meiotic divisions. Here, we summarize the main differences between mitotic and meiotic cell divisions, and explain why meiotic divisions pose special challenges for correct chromosome segregation. The less-known meiotic roles of the SAC kinases are described, with a focus on two model systems: yeast and mouse oocytes. The meiotic roles of the canonical checkpoint kinases Bub1, Mps1, the pseudokinase BubR1 (Mad3), and Aurora B and C (Ipl1) will be discussed. Insights into the molecular signaling pathways that bring about the special chromosome segregation pattern during meiosis will help us understand why human oocytes are so frequently aneuploid. PMID:29322045

  17. Multiple Duties for Spindle Assembly Checkpoint Kinases in Meiosis

    Directory of Open Access Journals (Sweden)

    Adele L. Marston

    2017-12-01

    Full Text Available Cell division in mitosis and meiosis is governed by evolutionary highly conserved protein kinases and phosphatases, controlling the timely execution of key events such as nuclear envelope breakdown, spindle assembly, chromosome attachment to the spindle and chromosome segregation, and cell cycle exit. In mitosis, the spindle assembly checkpoint (SAC controls the proper attachment to and alignment of chromosomes on the spindle. The SAC detects errors and induces a cell cycle arrest in metaphase, preventing chromatid separation. Once all chromosomes are properly attached, the SAC-dependent arrest is relieved and chromatids separate evenly into daughter cells. The signaling cascade leading to checkpoint arrest depends on several protein kinases that are conserved from yeast to man. In meiosis, haploid cells containing new genetic combinations are generated from a diploid cell through two specialized cell divisions. Though apparently less robust, SAC control also exists in meiosis. Recently, it has emerged that SAC kinases have additional roles in executing accurate chromosome segregation during the meiotic divisions. Here, we summarize the main differences between mitotic and meiotic cell divisions, and explain why meiotic divisions pose special challenges for correct chromosome segregation. The less-known meiotic roles of the SAC kinases are described, with a focus on two model systems: yeast and mouse oocytes. The meiotic roles of the canonical checkpoint kinases Bub1, Mps1, the pseudokinase BubR1 (Mad3, and Aurora B and C (Ipl1 will be discussed. Insights into the molecular signaling pathways that bring about the special chromosome segregation pattern during meiosis will help us understand why human oocytes are so frequently aneuploid.

  18. European immigration a sourcebook

    CERN Document Server

    Triandafyllidou, Anna

    2016-01-01

    Fully updated and containing chapters on the new EU member states and the attempt to form a common EU migration policy, this new edition of European Immigration: A Sourcebook provides a comprehensive overview of the trends and developments in migration in all EU countries. With chapters following a common structure to facilitate direct international comparisons, it not only examines the internal affairs of each member state, but also explores both migratory trends within the EU itself and the implications for European immigration of wider global events, including the Arab Spring and the world financial crisis.

  19. Predictors of responses to immune checkpoint blockade in advanced melanoma

    DEFF Research Database (Denmark)

    Jacquelot, N; Roberti, M P; Enot, D P

    2017-01-01

    Immune checkpoint blockers (ICB) have become pivotal therapies in the clinical armamentarium against metastatic melanoma (MMel). Given the frequency of immune related adverse events and increasing use of ICB, predictors of response to CTLA-4 and/or PD-1 blockade represent unmet clinical needs....... Using a systems biology-based approach to an assessment of 779 paired blood and tumor markers in 37 stage III MMel patients, we analyzed association between blood immune parameters and the functional immune reactivity of tumor-infiltrating cells after ex vivo exposure to ICB. Based on this assay, we...

  20. Central Tolerance Blockade to Augment Checkpoint Immunotherapy in Melanoma

    Science.gov (United States)

    2017-09-01

    expressed at higher levels in medullary thymic epithelial cells (mTECs) than in cortical thymic epithelial cells (cTECs), addition of anti-RANKL antibody...relative Aire expression by quantitative RT-PCR in cultured thymic tissue . 12-15 90% Subtask 3. Culture human thymus sections with OPG-Fc or vehicle...PCR in cultured thymic tissue . 15-18 90% ACURO approval 13-14 100% Major Task 1. Effect of concurrent anti-RANKL and checkpoint inhibitor

  1. Employers’ Openness to Labour Immigrants

    Directory of Open Access Journals (Sweden)

    Asta Mikalauskiene

    2017-10-01

    Full Text Available The paper presents the elucidation of the concept of migration and theories describing the process of migration, determines the issue of openness to immigration and presents its theoretical explanation.. The analysis of the empirical studies conducted in Lithuania assessing the openness of employers to labour immigrants was performed including the analysis of immigration trends in this country. The factors determining the attitudes towards immigration and immigrants are presented being divided into the main groups of economic and social-cultural factors.

  2. Conformation-specific anti-Mad2 monoclonal antibodies for the dissection of checkpoint signaling

    DEFF Research Database (Denmark)

    Sedgwick, Garry G; Larsen, Marie Sofie Yoo; Lischetti, Tiziana

    2016-01-01

    The spindle assembly checkpoint (SAC) ensures accurate chromosome segregation during mitosis by delaying the activation of the anaphase-promoting complex/cyclosome (APC/C) in response to unattached kinetochores. The Mad2 protein is essential for a functional checkpoint because it binds directly t...

  3. Space Reclamation for Uncoordinated Checkpointing in Message-Passing Systems. Ph.D. Thesis

    Science.gov (United States)

    Wang, Yi-Min

    1993-01-01

    Checkpointing and rollback recovery are techniques that can provide efficient recovery from transient process failures. In a message-passing system, the rollback of a message sender may cause the rollback of the corresponding receiver, and the system needs to roll back to a consistent set of checkpoints called recovery line. If the processes are allowed to take uncoordinated checkpoints, the above rollback propagation may result in the domino effect which prevents recovery line progression. Traditionally, only obsolete checkpoints before the global recovery line can be discarded, and the necessary and sufficient condition for identifying all garbage checkpoints has remained an open problem. A necessary and sufficient condition for achieving optimal garbage collection is derived and it is proved that the number of useful checkpoints is bounded by N(N+1)/2, where N is the number of processes. The approach is based on the maximum-sized antichain model of consistent global checkpoints and the technique of recovery line transformation and decomposition. It is also shown that, for systems requiring message logging to record in-transit messages, the same approach can be used to achieve optimal message log reclamation. As a final topic, a unifying framework is described by considering checkpoint coordination and exploiting piecewise determinism as mechanisms for bounding rollback propagation, and the applicability of the optimal garbage collection algorithm to domino-free recovery protocols is demonstrated.

  4. Immigrants' location preferences

    DEFF Research Database (Denmark)

    Damm, Anna Piil

    This paper exploits a spatial dispersal policy for refugee immigrants to estimate the importance of local and regional factors for refugees' location preferences. The main results of a mixed proportional hazard competing risks model are that placed refugees react to high regional unemployment...

  5. Encounters with immigrant customers

    DEFF Research Database (Denmark)

    Mygind, Anna; Espersen, Sacha; Nørgaard, Lotte Stig

    2013-01-01

    were not sufficiently assessed at the counter (n = 55, 65%), and that their latest encounter with an immigrant customer was less satisfactory than a similar encounter with an ethnic Danish customer (n = 48, 57%) (significantly more pharmacists than assistants: odds ratio, OR, 3.19; 95% confidence...

  6. Wealth & Immigration in Denmark

    DEFF Research Database (Denmark)

    Dreyer, Johannes Kabderian; Wolffsen, Poul; Mortensen, Mia

    2014-01-01

    Applying newly developed methods this paper quantifies human capital in Denmark and analyzes highly qualified immigration as a potential source of wealth generation. In order to quantify human capital, we use the methodology of Lettau and Ludvigson (2001, 2004), Zhang (2006) and Dreyer et al. (2013...

  7. Academic Mobility and Immigration

    Science.gov (United States)

    Tremblay, Karine

    2005-01-01

    In the late 1990s, sustained economic growth in most Organisation for Economic Cooperation and Development (OECD) countries and the development of the information economy led to a considerable increase in migration of highly skilled individuals, especially in science and technology. Some OECD countries relaxed their immigration policies to attract…

  8. Immigration policy index

    Czech Academy of Sciences Publication Activity Database

    Vikhrov, Dmytro

    2017-01-01

    Roč. 25, č. 1 (2017), s. 3-46 ISSN 0967-0750 Institutional support: Progres-Q24 Keywords : immigration policy * visa * differences-in-differences estimation Subject RIV: AH - Economics OBOR OECD: Applied Economics , Econometrics Impact factor: 0.479, year: 2016

  9. Gay Immigrants and Grindr

    DEFF Research Database (Denmark)

    Shield, Andrew DJ

    2018-01-01

    In this (open-access) essay, I assess the idea that Grindr and related apps render urban gay spaces obsolete, and offer three counter-arguments based on my research with immigrants and tourists who use Grindr. In short: newcomers who use Grindr might actually bring new life to queer urban spaces...

  10. Immigrants in the Working Environment

    Directory of Open Access Journals (Sweden)

    Maria Vlachadi

    2014-09-01

    Full Text Available Immigration constitutes an all time and multi-dimensional social phenomenon. There are quite a few people that in every time period seek a new place of residence and employment, in order to be able to survive or get a better life. The causes which lead to immigration are various and the immigration itself affects not only the immigrants but also the countries of departure and arrival. The immigration phenomenon has occupied and continues to occupy the majority of countries, among which is Greece which has been one of the new host countries for immigrants. The moving of the population presents when the social and economic environment in which an individual lives and moves, does not provide him with the capability to fulfill his pursuits and satisfy his ambitions. The most frequent reason of immigration nowadays is the economic factor and the objective of the individual that immigrates is finding work. In the present project we will study unemployment and employment in the host countries and more specifically in Greece. In Greece during the last years there appears to be an intense influx of immigrants converting it from a departure country to a host country for immigrants. What happens with the working conditions and insurance, how does immigration affect the unemployment of the permanent population, in what kind of jobs are immigrants occupied and do age and sex play a role in finding work? These are some of the questions we are called to answer through this project. The project not only will deal with how immigration affects the working market but also the economy in general (Cholezas and Tsakloglou, 2008. The research part of the project is based on the Greek and European Statistics Service. The statistical data are presented in the form of charts and diagrams. The data actually concern the legal immigrants in the area of Greece and countries of the E.U. (Vgenopoulos, 1988.

  11. Immigrant Capital and Entrepreneurial Opportunities

    Directory of Open Access Journals (Sweden)

    Malavika Sundararajan

    2016-01-01

    Full Text Available Objective: The main objective of this study is to define and operationalize the concept of immigrant capital, a key factor that differentiates immigrant from host country entrepreneurs in how they recognize and start new ventures. Research Design & Methods: A detailed analysis of contemporary immigrant entrepreneurship and opportunity recognition literature was carried out. Using grounded theory, we synthesized the outcomes from the analysis of eight Canadian and U.S. case studies of successful immigrant entrepreneurs with the key findings from the literature to define and develop a model of immigrant capital. Findings: Based on our grounded theory development process we show that the concept of immigrant capital as a distillate of human, cultural, economic and social capital that goes beyond expected opportunity recognition (OR drivers like prior knowledge and prior experience to differentiate and enhance the immigrant entrepreneur’s ability to recognize business opportunities compared to host country entrepreneurs. We found immigrant capital to be a consequence of being boundary spanners in host and home country networks. Implications & Recommendations: Understanding a unique resource like immigrant capital, will help immigrant as well as host country entrepreneurs further develop their opportunity recognition ability by bridging gaps and fulfilling the needs for both, immigrant and host country consumers. Contribution & Value Added: The main contribution is the theoretical development, identification and definition of the immigrant capital model and propositions that will articulate the factors that lead to the conceptualization and operationalization of immigrant capital. Furthermore, the immigrant capital model can serve host country entrepreneurs to develop cross-cultural networks and jump-start entrepreneurial activities in their home countries as well as learn how to expand their operations into global markets.

  12. Rituximab does not reset defective early B cell tolerance checkpoints

    Science.gov (United States)

    Chamberlain, Nicolas; Massad, Christopher; Oe, Tyler; Cantaert, Tineke; Herold, Kevan C.; Meffre, Eric

    2015-01-01

    Type 1 diabetes (T1D) patients show abnormalities in early B cell tolerance checkpoints, resulting in the accumulation of large numbers of autoreactive B cells in their blood. Treatment with rituximab, an anti-CD20 mAb that depletes B cells, has been shown to preserve β cell function in T1D patients and improve other autoimmune diseases, including rheumatoid arthritis and multiple sclerosis. However, it remains largely unknown how anti–B cell therapy thwarts autoimmunity in these pathologies. Here, we analyzed the reactivity of Abs expressed by single, mature naive B cells from 4 patients with T1D before and 52 weeks after treatment to determine whether rituximab resets early B cell tolerance checkpoints. We found that anti–B cell therapy did not alter the frequencies of autoreactive and polyreactive B cells, which remained elevated in the blood of all patients after rituximab treatment. Moreover, the limited proliferative history of autoreactive B cells after treatment revealed that these clones were newly generated B cells and not self-reactive B cells that had escaped depletion and repopulated the periphery through homeostatic expansion. We conclude that anti–B cell therapy may provide a temporary dampening of autoimmune processes through B cell depletion. However, repletion with autoreactive B cells may explain the relapse that occurs in many autoimmune patients after anti–B cell therapy. PMID:26642366

  13. Immunotherapy targeting immune check-point(s) in brain metastases.

    Science.gov (United States)

    Di Giacomo, Anna Maria; Valente, Monica; Covre, Alessia; Danielli, Riccardo; Maio, Michele

    2017-08-01

    Immunotherapy with monoclonal antibodies (mAb) directed to different immune check-point(s) is showing a significant clinical impact in a growing number of human tumors of different histotype, both in terms of disease response and long-term survival patients. In this rapidly changing scenario, treatment of brain metastases remains an high unmeet medical need, and the efficacy of immunotherapy in these highly dismal clinical setting remains to be largely demonstrated. Nevertheless, up-coming observations are beginning to suggest a clinical potential of cancer immunotherapy also in brain metastases, regardless the underlying tumor histotype. These observations remain to be validated in larger clinical trials eventually designed also to address the efficacy of therapeutic mAb to immune check-point(s) within multimodality therapies for brain metastases. Noteworthy, the initial proofs of efficacy on immunotherapy in central nervous system metastases are already fostering clinical trials investigating its therapeutic potential also in primary brain tumors. We here review ongoing immunotherapeutic approaches to brain metastases and primary brain tumors, and the foreseeable strategies to overcome their main biologic hurdles and clinical challenges. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Avelumab: combining immune checkpoint inhibition and antibody-dependent cytotoxicity.

    Science.gov (United States)

    Hamilton, Gerhard; Rath, Barbara

    2017-04-01

    Immune checkpoint inhibition holds great promise for selected tumors. The human monoclonal antibody (mAB) avelumab is directed to programmed death ligand-1 (PD-L1) and is supposed to inhibit the immunosuppressive PD-L1/PD-1 interaction and, furthermore, effect antibody-dependent cytotoxicity (ADCC) lysis of tumor cells. Areas covered: This article presents an overview of the current means to activate the antitumor immune defense by targeting PD-1 or PD-L1 with mABs and their possible role in ADCC-mediated tumor cell elimination. Expert opinion: Avelumab contains a Fc region which can bind cognate receptors on immune effector cells and induce ADCC-mediated tumor cell lysis, in contrast to other mABs directed to PD-1/PD-L1 which lack the ability to trigger ADCC due to belonging to the IgG4 subclass or possessing a mutated Fc region. Preclinical and clinical data indicate that avelumab can be safely administered to cancer patients with a toxicity profile comparable to other mABs and without lysis of PD-L1-positive activated immune cells. This antibody yielded durable responses in a phase II trial in advanced Merkel cell carcinoma patients. Tumor cell lysis by avelumab prevents cells from resorting to alternative checkpoints as shown by targeting PD-1 and the upregulation of TIM-3.

  15. Cenp-meta is required for sustained spindle checkpoint

    Directory of Open Access Journals (Sweden)

    Thomas Rubin

    2014-05-01

    Full Text Available Cenp-E is a kinesin-like motor protein required for efficient end-on attachment of kinetochores to the spindle microtubules. Cenp-E immunodepletion in Xenopus mitotic extracts results in the loss of mitotic arrest and massive chromosome missegregation, whereas its depletion in mammalian cells leads to chromosome segregation defects despite the presence of a functional spindle assembly checkpoint (SAC. Cenp-meta has previously been reported to be the Drosophila homolog of vertebrate Cenp-E. In this study, we show that cenp-metaΔ mutant neuroblasts arrest in mitosis when treated with colchicine. cenp-metaΔ mutant cells display a mitotic delay. Yet, despite the persistence of the two checkpoint proteins Mad2 and BubR1 on unattached kinetochores, these cells eventually enter anaphase and give rise to highly aneuploid daughter cells. Indeed, we find that cenp-metaΔ mutant cells display a slow but continuous degradation of cyclin B, which eventually triggers the mitotic exit observed. Thus, our data provide evidence for a role of Cenp-meta in sustaining the SAC response.

  16. 8 CFR 1003.10 - Immigration judges.

    Science.gov (United States)

    2010-01-01

    ... 8 Aliens and Nationality 1 2010-01-01 2010-01-01 false Immigration judges. 1003.10 Section 1003.10 Aliens and Nationality EXECUTIVE OFFICE FOR IMMIGRATION REVIEW, DEPARTMENT OF JUSTICE GENERAL PROVISIONS EXECUTIVE OFFICE FOR IMMIGRATION REVIEW Office of the Chief Immigration Judge § 1003.10 Immigration judges...

  17. 22 CFR 42.33 - Diversity immigrants.

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Diversity immigrants. 42.33 Section 42.33 Foreign Relations DEPARTMENT OF STATE VISAS VISAS: DOCUMENTATION OF IMMIGRANTS UNDER THE IMMIGRATION AND NATIONALITY ACT, AS AMENDED Immigrants Subject to Numerical Limitations § 42.33 Diversity immigrants. (a...

  18. Portrayal of Immigrants in Newsmagazines

    Directory of Open Access Journals (Sweden)

    Goran Goldberger

    2004-03-01

    Full Text Available This article analyzes how United States newsmagazines represented immigrants in the aftermath of September 11th terrorist attacks. Methodologically, the paper uses the frame analysis from a social constructivist standpoint, identifying the four functions of frame, as defined by Entman. Three months prior to the attacks, newsmagazines framed immigrants as “needed” and, in most cases, they portrayed them positively. In the period after the attacks, the frame shifted and newsmagazines started representing immigrants as “feared”, potential harborers of terrorists, and so on. Before the attacks, illegal immigrants were represented as the greatest immigration problem. After the attacks, the attention of newsmagazines shifted to legal immigrants with terrorist intentions. The results suggest that the issue of immigrants and immigration policy in the media collided with the threat of terrorism as a foreign policy issue. Thus, it became a security issue that influenced the representation of immigrants. In newsmagazines’ portrayal of immigrants, political features became more prominent than economic ones.

  19. Parallelization and checkpointing of GPU applications through program transformation

    Energy Technology Data Exchange (ETDEWEB)

    Solano-Quinde, Lizandro Damian [Iowa State Univ., Ames, IA (United States)

    2012-01-01

    GPUs have emerged as a powerful tool for accelerating general-purpose applications. The availability of programming languages that makes writing general-purpose applications for running on GPUs tractable have consolidated GPUs as an alternative for accelerating general purpose applications. Among the areas that have benefited from GPU acceleration are: signal and image processing, computational fluid dynamics, quantum chemistry, and, in general, the High Performance Computing (HPC) Industry. In order to continue to exploit higher levels of parallelism with GPUs, multi-GPU systems are gaining popularity. In this context, single-GPU applications are parallelized for running in multi-GPU systems. Furthermore, multi-GPU systems help to solve the GPU memory limitation for applications with large application memory footprint. Parallelizing single-GPU applications has been approached by libraries that distribute the workload at runtime, however, they impose execution overhead and are not portable. On the other hand, on traditional CPU systems, parallelization has been approached through application transformation at pre-compile time, which enhances the application to distribute the workload at application level and does not have the issues of library-based approaches. Hence, a parallelization scheme for GPU systems based on application transformation is needed. Like any computing engine of today, reliability is also a concern in GPUs. GPUs are vulnerable to transient and permanent failures. Current checkpoint/restart techniques are not suitable for systems with GPUs. Checkpointing for GPU systems present new and interesting challenges, primarily due to the natural differences imposed by the hardware design, the memory subsystem architecture, the massive number of threads, and the limited amount of synchronization among threads. Therefore, a checkpoint/restart technique suitable for GPU systems is needed. The goal of this work is to exploit higher levels of parallelism and

  20. Intolerance toward immigrants in Switzerland

    DEFF Research Database (Denmark)

    Freitag, Markus; Rapp, Carolin

    2013-01-01

    Intolerance toward immigrants has recently reached noticeable highs in Switzerland. Referring to the conflict theory, the perception of a specific group as a threat tends to lead to intolerance toward that group. The expectation of a negative relationship between threat and tolerance is neverthel......Intolerance toward immigrants has recently reached noticeable highs in Switzerland. Referring to the conflict theory, the perception of a specific group as a threat tends to lead to intolerance toward that group. The expectation of a negative relationship between threat and tolerance...... that Swiss who view rising immigration to mean a loss of economic privileges and an erosion of Swiss cultural values are less tolerant toward immigrants. Moreover, our results indicate that contact with immigrants may moderate this effect. However, not all group settings are able to reduce the perceived...... threats in a similar way, and not all sorts of social contact are able to foster tolerance toward immigrants....

  1. A genetic screen identifies BRCA2 and PALB2 as key regulators of G2 checkpoint maintenance

    DEFF Research Database (Denmark)

    Menzel, Tobias; Nähse-Kumpf, Viola; Kousholt, Arne Nedergaard

    2011-01-01

    To identify key connections between DNA-damage repair and checkpoint pathways, we performed RNA interference screens for regulators of the ionizing radiation-induced G2 checkpoint, and we identified the breast cancer gene BRCA2. The checkpoint was also abrogated following depletion of PALB2......, an interaction partner of BRCA2. BRCA2 and PALB2 depletion led to premature checkpoint abrogation and earlier activation of the AURORA A-PLK1 checkpoint-recovery pathway. These results indicate that the breast cancer tumour suppressors and homologous recombination repair proteins BRCA2 and PALB2 are main...

  2. Immigrants in the Sexual Revolution

    DEFF Research Database (Denmark)

    Shield, Andrew DJ

    newspapers, foreign worker organizations’ archives, and interviews, this book shows that immigrants in the Netherlands and Denmark held a variety of viewpoints about European gender and sexual cultures. Some immigrants felt solidarity with, and even participated in, European social movements that changed...... norms and laws in favor of women’s equality, gay and lesbian rights, and sexual liberation. These histories challenge today’s politicians and journalists who strategically link immigration to sexual conservatism, misogyny, and homophobia....

  3. Immigrant Capital and Entrepreneurial Opportunities

    OpenAIRE

    Malavika Sundararajan; Binod Sundararajan

    2016-01-01

    Objective: The main objective of this study is to define and operationalize the concept of immigrant capital, a key factor that differentiates immigrant from host country entrepreneurs in how they recognize and start new ventures. Research Design & Methods: A detailed analysis of contemporary immigrant entrepreneurship and opportunity recognition literature was carried out. Using grounded theory, we synthesized the outcomes from the analysis of eight Canadian and U.S. case studies of successf...

  4. Ethnic pluralism, immigration and entrepreneurship

    OpenAIRE

    Mickiewicz, T; Hart, M; Nyakudya, FW; Theodorakopoulos, N

    2017-01-01

    We consider the effects of immigration and ethnicity on entrepreneurship, distinguishing between the individual traits and the environmental characteristics. We look beyond the resource-opportunity framework and occupational choice: culture and values matter. Yet, instead of assigning the latter to specific ethnic features, we relate them to both immigration, and to the social environment defined by the share of immigrants, and by ethnic diversity. Empirical evidence we provide is based on Gl...

  5. EMODnet MedSea Checkpoint for sustainable Blue Growth

    Science.gov (United States)

    Moussat, Eric; Pinardi, Nadia; Manzella, Giuseppe; Blanc, Frederique

    2016-04-01

    The EMODNET checkpoint is a wide monitoring system assessment activity aiming to support the sustainable Blue Growth at the scale of the European Sea Basins by: 1) Clarifying the observation landscape of all compartments of the marine environment including Air, Water, Seabed, Biota and Human activities, pointing out to the existing programs, national, European and international 2) Evaluating fitness for use indicators that will show the accessibility and usability of observation and modeling data sets and their roles and synergies based upon selected applications by the European Marine Environment Strategy 3) Prioritizing the needs to optimize the overall monitoring Infrastructure (in situ and satellite data collection and assembling, data management and networking, modeling and forecasting, geo-infrastructure) and release recommendations for evolutions to better meet the application requirements in view of sustainable Blue Growth The assessment is designed for : - Institutional stakeholders for decision making on observation and monitoring systems - Data providers and producers to know how their data collected once for a given purpose could fit other user needs - End-users interested in a regional status and possible uses of existing monitoring data Selected end-user applications are of paramount importance for: (i) the blue economy sector (offshore industries, fisheries); (ii) marine environment variability and change (eutrophication, river inputs and ocean climate change impacts); (iii) emergency management (oil spills); and (iv) preservation of natural resources and biodiversity (Marine Protected Areas). End-user applications generate innovative products based on the existing observation landscape. The fitness for use assessment is made thanks to the comparison of the expected product specifications with the quality of the product derived from the selected data. This involves the development of checkpoint information and indicators based on Data quality and

  6. Acute inflammatory thyromegaly following checkpoint inhibition: A new imaging entity?

    Directory of Open Access Journals (Sweden)

    Erik H. Middlebrooks, MD

    2018-02-01

    Full Text Available Immune checkpoint blockade (CPB utilizing such agents as ipilimumab, nivolumab, or pembrolizumab has revolutionized melanoma therapy and has seen continued utilization in numerous other malignancies in recent years. However, these agents come at the price of inflammatory immune-related adverse events. Despite the increasing recognition of biochemical thyroid dysfunction associated with CPB, information regarding potential imaging findings is sparse. We describe the first 2 cases of acute thyroiditis following CPB presenting as diffuse thyromegaly documented by computed tomography, ultrasound, and iodine uptake imaging. Given the rise in the use of CPB, it is important for radiologists to recognize potential imaging manifestations of therapy immune-related adverse events to avoid erroneous diagnosis and to prompt the biochemical investigation of thyroid function.

  7. The CD47-SIRPα signaling axis as an innate immune checkpoint in cancer.

    Science.gov (United States)

    Matlung, Hanke L; Szilagyi, Katka; Barclay, Neil A; van den Berg, Timo K

    2017-03-01

    Immune checkpoint inhibitors, including those targeting CTLA-4/B7 and the PD-1/PD-L1 inhibitory pathways, are now available for clinical use in cancer patients, with other interesting checkpoint inhibitors being currently in development. Most of these have the purpose to promote adaptive T cell-mediated immunity against cancer. Here, we review another checkpoint acting to potentiate the activity of innate immune cells towards cancer. This innate immune checkpoint is composed of what has become known as the 'don't-eat me' signal CD47, which is a protein broadly expressed on normal cells and often overexpressed on cancer cells, and its counter-receptor, the myeloid inhibitory immunoreceptor SIRPα. Blocking CD47-SIRPα interactions has been shown to promote the destruction of cancer cells by phagocytes, including macrophages and neutrophils. Furthermore, there is growing evidence that targeting of the CD47-SIRPα axis may also promote antigen-presenting cell function and thereby stimulate adaptive T cell-mediated anti-cancer immunity. The development of CD47-SIRPα checkpoint inhibitors and the potential side effects that these may have are discussed. Collectively, this identifies the CD47-SIRPα axis as a promising innate immune checkpoint in cancer, and with data of the first clinical studies with CD47-SIRPα checkpoint inhibitors expected within the coming years, this is an exciting and rapidly developing field. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. [Tuberculosis and immigration].

    Science.gov (United States)

    Salas-Coronas, Joaquín; Rogado-González, M Cruz; Lozano-Serrano, Ana Belén; Cabezas-Fernández, M Teresa

    2016-04-01

    The incidence of tuberculosis worldwide is declining. However, in Western countries this decline is slower due to the impact of immigration. Tuberculosis in the immigrant population is related to health status in the country of origin and with overcrowding and poverty conditions in the host country. Immigrants with tuberculosis are younger, have a higher prevalence of extrapulmonary forms, greater proportion of drug resistance and higher treatment default rates than those of natives. New molecular techniques not only reduce diagnostic delay time but also allow the rapid identification of resistances and improve knowledge of transmission patterns. It is necessary to implement measures to improve treatment compliance in this population group like facilitating access to health card, the use of fixed-dose combination drugs, the participation of cultural mediators and community health workers and gratuity of drugs. Copyright © 2016 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  9. [Immigration to Venezuela].

    Science.gov (United States)

    Picouet, M; Pellegrino, A; Papail, J

    1986-11-01

    Immigration to Venezuela is examined using census data with the focus on the period 1971-1981. A brief overview of trends since the beginning of the twentieth century is first presented. The analysis indicates that "immigration to Venezuela is clearly of a short-term nature. Flows follow job opportunities and adjust to the labour market and to the financial capacity of the exchange market. The large increase of migratory movements to Venezuela in the 1970's is characterized by a diversification of their places of origin and by a greater instability. To a large extent, the migrants are illegal, especially those coming from Colombia and the Caribbean islands. Because of the crisis of the early 1980's, which is now worsened by the down trend of both oil prices and the U.S. dollar, Venezuela has become less attractive to immigrants, particularly from neighbouring countries." The authors observe that migrants in Venezuela are not well integrated and may depart, disrupting the labor supply in certain technical and specialized occupations (SUMMARY IN ENG AND SPA) excerpt

  10. Role of Immune Checkpoint Inhibitors in Small Cell Lung Cancer.

    Science.gov (United States)

    Cooper, Maryann R; Alrajhi, Abdullah M; Durand, Cheryl R

    Small cell lung cancer (SCLC) accounts for approximately 13% of all lung cancer diagnoses each year. SCLC is characterized by a rapid doubling time, early metastatic spread, and an unfavorable prognosis overall. Most patients with SCLC will respond to initial treatment; however, the majority will experience a disease recurrence and response to second-line therapies is poor. Immune checkpoint inhibitors may be an option given the success in other diseases. A literature search was conducted using Medline (1946-July week 1, 2017) and Embase (1996-2017 week 28) with the search terms small cell lung cancer combined with nivolumab or ipilimumab or pembrolizumab or atezolizumab or tremelimumab or durvalumab. Five clinical trials, including extended follow-up for 2, that evaluated immune checkpoint inhibitors in limited stage or extensive stage SCLC were included. In 2 phase 2 trials, ipilimumab was added to upfront chemotherapy. In both trials, an improvement in progression-free survival was seen. Toxicity, when combined with a platinum and etoposide, was significant. In a confirmatory phase 3 trial, ipilimumab did not prolong overall survival when added to first-line chemotherapy. Overall, response rates were similar between the placebo and ipilimumab groups. A phase 1/2 trial evaluated nivolumab alone or in combination with ipilimumab in recurrent SCLC. Results revealed that nivolumab monotherapy and the combination of nivolumab and ipilimumab were relatively safe and had antitumor activity. Pembrolizumab has been evaluated in a multicohort, phase 1b trial. Preliminary data showed a durable response in the second-line setting. Given the lack of overall survival data and significant toxicity associated with the combination of ipilimumab with first-line chemotherapy, this treatment is not a reasonable option at this time. Nivolumab alone or in combination with ipilimumab is a valid option for recurrent SCLC.

  11. The Self-Employment Experience of Immigrants

    OpenAIRE

    George J. Borjas

    1986-01-01

    Self-employment is an important aspect of the immigrant experience in the labor market. Self-employment rates for immigrants exceed 15 percent for some national groups. This paper addresses three related questions on the self-employment experience of immigrants. First, how do self-employment rates of immigrants compare to those of native-born men? Second, is there an "assimilation" effect on the self-employment propensity of immigrants? Finally, are the more recent waves of immigrants facing ...

  12. Immigrant language barriers and house prices

    OpenAIRE

    Fischer, Andreas M.

    2011-01-01

    Are language skills important in explaining the nexus between house prices and immigrant inflows? The language barrier hypothesis says immigrants from a non common language country value amenities more than immigrants from common language countries.> ; In turn, immigrants from non common language countries are less price sensitive to house price changes than immigrants from a common language country. Tests of the language barrier hypothesis with Swiss house prices show that an immigration inf...

  13. Immigration Enforcement Actions - Annual Report

    Data.gov (United States)

    Department of Homeland Security — Each year, the Department of Homeland Security (DHS) undertakes immigration enforcement actions involving hundreds of thousands of foreign nationals. These actions...

  14. From Multiculturalism to Immigration Shock

    OpenAIRE

    Paul Lauter

    2009-01-01

    Immigration is a tense political topic in virtually every Western country, and in many others as well. In fact, immigration is an international issue: 3 percent of the world's population, 191,000,000 people, now live in countries other than those in which they were born. This paper discusses why immigration is so fraught, the relation of the crisis over immigration to the growing fracture of the Western world's economy, as well as to terrorism like September 11 and the train bombings...

  15. The pachytene checkpoint and its relationship to evolutionary patterns of polyploidization and hybrid sterility.

    Science.gov (United States)

    Li, X C; Barringer, B C; Barbash, D A

    2009-01-01

    Sterility is a commonly observed phenotype in interspecific hybrids. Sterility may result from chromosomal or genic incompatibilities, and much progress has been made toward understanding the genetic basis of hybrid sterility in various taxa. The underlying mechanisms causing hybrid sterility, however, are less well known. The pachytene checkpoint is a meiotic surveillance system that many organisms use to detect aberrant meiotic products, in order to prevent the production of defective gametes. We suggest that activation of the pachytene checkpoint may be an important mechanism contributing to two types of hybrid sterility. First, the pachytene checkpoint may form the mechanistic basis of some gene-based hybrid sterility phenotypes. Second, the pachytene checkpoint may be an important mechanism that mediates chromosomal-based hybrid sterility phenotypes involving gametes with non-haploid (either non-reduced or aneuploid) chromosome sets. Studies in several species suggest that the strength of the pachytene checkpoint is sexually dimorphic, observations that warrant future investigation into whether such variation may contribute to differences in patterns of sterility between male and female interspecific hybrids. In addition, plants seem to lack the pachytene checkpoint, which correlates with increased production of unreduced gametes and a higher incidence of polyploid species in plants versus animals. Although the pachytene checkpoint occurs in many animals and in fungi, at least some of the genes that execute the pachytene checkpoint are different among organisms. This finding suggests that the penetrance of the pachytene checkpoint, and even its presence or absence can evolve rapidly. The surprising degree of evolutionary flexibility in this meiotic surveillance system may contribute to the observed variation in patterns of hybrid sterility and in rates of polyploidization.

  16. NEK11: linking CHK1 and CDC25A in DNA damage checkpoint signaling

    DEFF Research Database (Denmark)

    Sørensen, Claus Storgaard; Melixetian, Marina; Klein, Ditte Kjaersgaard

    2010-01-01

    The DNA damage induced G(2)/M checkpoint is an important guardian of the genome that prevents cell division when DNA lesions are present. The checkpoint prevents cells from entering mitosis by degrading CDC25A, a key CDK activator. CDC25A proteolysis is controlled by direct phosphorylation events...... is required for beta-TrCP mediated CDC25A polyubiquitylation and degradation. The activity of NEK11 is in turn controlled by CHK1 that activates NEK11 via phosphorylation on serine 273. Since inhibition of NEK11 activity forces checkpoint-arrested cells into mitosis and cell death, NEK11 is, like CHK1...

  17. Immigration and Religion in Denmark

    DEFF Research Database (Denmark)

    Christoffersen, Lisbet

    2009-01-01

    An overview over legal framework for immigration into Denmark, special clauses on religion as a parameter for residence permit and asylum in churches......An overview over legal framework for immigration into Denmark, special clauses on religion as a parameter for residence permit and asylum in churches...

  18. Immigrant Education: A Fact Sheet.

    Science.gov (United States)

    Aleman, Steven R.

    This report provides information on immigrant education in the United States in the areas of funding, participation, population, services, and allocation method. Additionally, it explores reauthorization issues confronting the Emergency Immigrant Education Act for fiscal year 1994. The report shows that: (1) there has been a steady decrease in…

  19. Identity Transformation of Korean Immigrants.

    Science.gov (United States)

    Kim, Saekyung; Gaa, John; Swank, Paul; Liberman, Dov

    Immigration is one of the most significant changes which can occur in one's lifetime. Immigrants struggle with their foreign environment and renewed crises; they suffer from "uprootedness" and "missed embeddedness" and have difficulty integrating their identity roles. Erikson's psychosocial development theory and Marcia's…

  20. An origin-deficient yeast artificial chromosome triggers a cell cycle checkpoint.

    Science.gov (United States)

    van Brabant, A J; Buchanan, C D; Charboneau, E; Fangman, W L; Brewer, B J

    2001-04-01

    Checkpoint controls coordinate entry into mitosis with the completion of DNA replication. Depletion of nucleotide precursors by treatment with the drug hydroxyurea triggers such a checkpoint response. However, it is not clear whether the signal for this hydroxyurea-induced checkpoint pathway is the presence of unreplicated DNA, or rather the persistence of single-stranded or damaged DNA. In a yeast artificial chromosome (YAC) we have engineered an approximately 170 kb region lacking efficient replication origins that allows us to explore the specific effects of unreplicated DNA on cell cycle progression. Replication of this YAC extends the length of S phase and causes cells to engage an S/M checkpoint. In the absence of Rad9 the YAC becomes unstable, undergoing deletions within the origin-free region.

  1. Top3 processes recombination intermediates and modulates checkpoint activity after DNA damage

    DEFF Research Database (Denmark)

    Mankouri, Hocine W; Hickson, Ian D

    2006-01-01

    Mutation of TOP3 in Saccharomyces cerevisiae causes poor growth, hyperrecombination, and a failure to fully activate DNA damage checkpoints in S phase. Here, we report that overexpression of a dominant-negative allele of TOP3, TOP3(Y356F), which lacks the catalytic (decatenation) activity of Top3......, the catalytic activity of Top3 is not required for DNA damage checkpoint activation, but it is required for normal S-phase progression after DNA damage. We also present evidence that the checkpoint-mediated cell cycle delay and persistence of X-shaped DNA molecules resulting from overexpression of TOP3(Y356F......) are downstream of Rad51 function. We propose that Top3 functions in S phase to both process homologous recombination intermediates and modulate checkpoint activity....

  2. An ATM-independent S-phase checkpoint response involves CHK1 pathway

    Science.gov (United States)

    Zhou, Xiang-Yang; Wang, Xiang; Hu, Baocheng; Guan, Jun; Iliakis, George; Wang, Ya

    2002-01-01

    After exposure to genotoxic stress, proliferating cells actively slow down the DNA replication through a S-phase checkpoint to provide time for repair. We report that in addition to the ataxia-telangiectasia mutated (ATM)-dependent pathway that controls the fast response, there is an ATM-independent pathway that controls the slow response to regulate the S-phase checkpoint after ionizing radiation in mammalian cells. The slow response of S-phase checkpoint, which is resistant to wortmannin, sensitive to caffeine and UCN-01, and related to cyclin-dependent kinase phosphorylation, is much stronger in CHK1 overexpressed cells, and it could be abolished by Chk1 antisense oligonucleotides. These results provide evidence that the ATM-independent slow response of S-phase checkpoint involves CHK1 pathway.

  3. Immune-checkpoint inhibitors in the era of precision medicine: What radiologists should know

    Energy Technology Data Exchange (ETDEWEB)

    Braschi-Amirfarzan, Marta; Tirumani, Sree Harsha; Hodi, Frank Stephan Jr; Nishno, Mizuki [Dept. of Radiology, Brigham and Women' s Hospital and Dana Farber Cancer Institute, Boston (United States)

    2017-01-15

    Over the past five years immune-checkpoint inhibitors have dramatically changed the therapeutic landscape of advanced solid and hematologic malignancies. The currently approved immune-checkpoint inhibitors include antibodies to cytotoxic T-lymphocyte antigen-4, programmed cell death (PD-1), and programmed cell death ligand (PD-L1 and PD-L2). Response to immune-checkpoint inhibitors is evaluated on imaging using the immune-related response criteria. Activation of immune system results in a unique toxicity profile termed immune-related adverse events. This article will review the molecular mechanism, clinical applications, imaging of immune-related response patterns and adverse events associated with immune-checkpoint inhibitors.

  4. Implication of the G2 checkpoint in the maintenance of genome integrity

    International Nuclear Information System (INIS)

    Piette, J.; Munoz, P.

    2000-01-01

    Checkpoints are surveillance mechanisms that block transitions, for instance in response to DNA damage. We summarize here here recent progress in the molecular characterization of the G 2 checkpoint which controls the entry into mitosis, and review new evidence which implicates de-regulated expression of checkpoint proteins and proteins involved in DNA damage repair in cancer development. These now exists good evidence that individuals who inherited mutations in genes involved in G 2 checkpoint and DNA damage repair are predisposed to the development of various types of cancer, their cells having a strong tendency to accumulate additional mutations. However, the occurrence of mutations of most of these genes in sporadic tumors has yet to be analysed more accurately. (authors)

  5. Immune-checkpoint inhibitors in the era of precision medicine: What radiologists should know

    International Nuclear Information System (INIS)

    Braschi-Amirfarzan, Marta; Tirumani, Sree Harsha; Hodi, Frank Stephan Jr; Nishno, Mizuki

    2017-01-01

    Over the past five years immune-checkpoint inhibitors have dramatically changed the therapeutic landscape of advanced solid and hematologic malignancies. The currently approved immune-checkpoint inhibitors include antibodies to cytotoxic T-lymphocyte antigen-4, programmed cell death (PD-1), and programmed cell death ligand (PD-L1 and PD-L2). Response to immune-checkpoint inhibitors is evaluated on imaging using the immune-related response criteria. Activation of immune system results in a unique toxicity profile termed immune-related adverse events. This article will review the molecular mechanism, clinical applications, imaging of immune-related response patterns and adverse events associated with immune-checkpoint inhibitors

  6. From Multiculturalism to Immigration Shock

    Directory of Open Access Journals (Sweden)

    Paul Lauter

    2009-02-01

    Full Text Available

    Immigration is a tense political topic in virtually every Western country, and in many others as well. In fact, immigration is an international issue: 3 percent of the world's population, 191,000,000 people, now live in countries other than those in which they were born. This paper discusses why immigration is so fraught, the relation of the crisis over immigration to the growing fracture of the Western world's economy, as well as to terrorism like September 11 and the train bombings in Madrid, Mumbai, and London, and how these factors—growing economic disparity, immigration, and terrorism—have altered one of the basic cultural phenomena of the United States in the last three decades, namely, what we call multiculturalism.

  7. From Multiculturalism to Immigration Shock

    Directory of Open Access Journals (Sweden)

    Paul Lauter

    2009-02-01

    Full Text Available Immigration is a tense political topic in virtually every Western country, and in many others as well. In fact, immigration is an international issue: 3 percent of the world's population, 191,000,000 people, now live in countries other than those in which they were born. This paper discusses why immigration is so fraught, the relation of the crisis over immigration to the growing fracture of the Western world's economy, as well as to terrorism like September 11 and the train bombings in Madrid, Mumbai, and London, and how these factors—growing economic disparity, immigration, and terrorism—have altered one of the basic cultural phenomena of the United States in the last three decades, namely, what we call multiculturalism.

  8. Religious and secular volunteering: A comparison between immigrants and non-immigrants in the Netherlands.

    NARCIS (Netherlands)

    Carabain, C.L.; Bekkers, R.H.F.P.

    2011-01-01

    Using new survey data from the Netherlands, we find that non-immigrants are more likely to volunteer for secular organisations than guest worker immigrants and postcolonial citizen immigrants. In contrast, non-immigrants are less likely to engage in religious volunteering than both immigrant groups.

  9. 78 FR 32989 - Visas: Documentation of Immigrants under the Immigration and Nationality Act, as Amended

    Science.gov (United States)

    2013-06-03

    ... Immigrants under the Immigration and Nationality Act, as Amended AGENCY: Department of State. ACTION: Final... aliens who seek immigrant visas and does not affect any small entities, as defined in 5 U.S.C. 601(6). C... with the following change: PART 42--VISAS: DOCUMENTATION OF IMMIGRANTS UNDER THE IMMIGRATION AND...

  10. Orchestration of DNA Damage Checkpoint Dynamics across the Human Cell Cycle.

    Science.gov (United States)

    Chao, Hui Xiao; Poovey, Cere E; Privette, Ashley A; Grant, Gavin D; Chao, Hui Yan; Cook, Jeanette G; Purvis, Jeremy E

    2017-11-22

    Although molecular mechanisms that prompt cell-cycle arrest in response to DNA damage have been elucidated, the systems-level properties of DNA damage checkpoints are not understood. Here, using time-lapse microscopy and simulations that model the cell cycle as a series of Poisson processes, we characterize DNA damage checkpoints in individual, asynchronously proliferating cells. We demonstrate that, within early G1 and G2, checkpoints are stringent: DNA damage triggers an abrupt, all-or-none cell-cycle arrest. The duration of this arrest correlates with the severity of DNA damage. After the cell passes commitment points within G1 and G2, checkpoint stringency is relaxed. By contrast, all of S phase is comparatively insensitive to DNA damage. This checkpoint is graded: instead of halting the cell cycle, increasing DNA damage leads to slower S phase progression. In sum, we show that a cell's response to DNA damage depends on its exact cell-cycle position and that checkpoints are phase-dependent, stringent or relaxed, and graded or all-or-none. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Undocumented immigration status and diabetes care among Mexican immigrants in two immigration "sanctuary" areas.

    Science.gov (United States)

    Iten, A Elizabeth; Jacobs, Elizabeth A; Lahiff, Maureen; Fernández, Alicia

    2014-04-01

    The objective of this study is to investigate the relationship between immigration status and the patient experience of health care, diabetes self-management, and clinical outcomes among Mexican immigrants with diabetes receiving health care in two immigration sanctuary cities. We used data from the Immigration, Culture and Health Care study, a cross-sectional survey and medical record study of low-income patients with diabetes recruited from public hospitals and community clinics in the San Francisco Bay Area and Chicago. Undocumented Mexican, documented Mexican immigrants, and US-born Mexican-Americans' health care experiences, diabetes self-management, and clinical outcomes were compared using multivariate linear and logistic regressions. We found no significant differences in reports of physician communication, or in measures of diabetes management between undocumented and documented immigrants. All three groups had similar clinical outcomes in glycemic, systolic blood pressure, and lipid control. These results indicate that, at least in some settings, undocumented Mexican immigrants with diabetes can achieve similar clinical outcomes and report similar health care experiences as documented immigrants and US-born Mexican-Americans.

  12. 8 CFR 1240.1 - Immigration judges.

    Science.gov (United States)

    2010-01-01

    ... 8 Aliens and Nationality 1 2010-01-01 2010-01-01 false Immigration judges. 1240.1 Section 1240.1 Aliens and Nationality EXECUTIVE OFFICE FOR IMMIGRATION REVIEW, DEPARTMENT OF JUSTICE IMMIGRATION... Immigration judges. (a) Authority. (1) In any removal proceeding pursuant to section 240 of the Act, the...

  13. 8 CFR 1240.41 - Immigration judges.

    Science.gov (United States)

    2010-01-01

    ... 8 Aliens and Nationality 1 2010-01-01 2010-01-01 false Immigration judges. 1240.41 Section 1240.41 Aliens and Nationality EXECUTIVE OFFICE FOR IMMIGRATION REVIEW, DEPARTMENT OF JUSTICE IMMIGRATION..., 1997) § 1240.41 Immigration judges. (a) Authority. In any proceeding conducted under this part the...

  14. The Changing Face of Immigration Law.

    Science.gov (United States)

    Nugent, Christopher

    2001-01-01

    Focuses on laws that influence U.S. immigration, such as the Illegal Immigration Reform and Immigrant Responsibility Act (1996), the Personal Responsibility and Work Opportunity Reconciliation Act (1996), the Anti-Terrorism and Effective Death Penalty Act (1996), and the Legal Immigration and Family Equity Act (2000). Includes discussion…

  15. The U.S. immigration crisis.

    Science.gov (United States)

    Stacey, G P; Lutton, W

    1985-01-01

    A review of the factors affecting immigration to the United States is presented. The authors develop the argument that present levels of immigration, particularly illegal immigration, are detrimental to U.S. interests, and that current global population trends will make this situation progressively worse. Stricter controls on immigration are considered.

  16. Crime and immigration: evidence from large immigrant waves

    OpenAIRE

    Brian Bell; Stephen Machin; Francesco Fasani

    2010-01-01

    This paper examines the relationship between immigration and crime in a setting where large migration flows offer an opportunity to carefully appraise whether the populist view that immigrants cause crime is borne out by rigorous evidence. We consider possible crime effects from two large waves of immigration that recently occurred in the UK. The first of these was the late 1990s/early 2000s wave of asylum seekers, and the second the large inflow of workers from EU accession countries that to...

  17. The making of an immigrant niche.

    Science.gov (United States)

    Waldinger, R

    1994-01-01

    "This article speaks to the conceptual and methodological issues in research on the making of an immigrant niche through a case study of immigrant professionals in New York City government." The author argues that "the growth of this immigrant niche resulted from changes in the relative supply of native workers and in the structure of employment, which opened the bureaucracy to immigrants and reduced native/immigrant competition. These shifts opened hiring portals; given the advantages of network hiring for workers and managers, and an immigrant propensity for government employment, network recruitment led to a rapid buildup in immigrant ranks." excerpt

  18. Resistance to checkpoint blockade therapy through inactivation of antigen presentation.

    Science.gov (United States)

    Sade-Feldman, Moshe; Jiao, Yunxin J; Chen, Jonathan H; Rooney, Michael S; Barzily-Rokni, Michal; Eliane, Jean-Pierre; Bjorgaard, Stacey L; Hammond, Marc R; Vitzthum, Hans; Blackmon, Shauna M; Frederick, Dennie T; Hazar-Rethinam, Mehlika; Nadres, Brandon A; Van Seventer, Emily E; Shukla, Sachet A; Yizhak, Keren; Ray, John P; Rosebrock, Daniel; Livitz, Dimitri; Adalsteinsson, Viktor; Getz, Gad; Duncan, Lyn M; Li, Bo; Corcoran, Ryan B; Lawrence, Donald P; Stemmer-Rachamimov, Anat; Boland, Genevieve M; Landau, Dan A; Flaherty, Keith T; Sullivan, Ryan J; Hacohen, Nir

    2017-10-26

    Treatment with immune checkpoint blockade (CPB) therapies often leads to prolonged responses in patients with metastatic melanoma, but the common mechanisms of primary and acquired resistance to these agents remain incompletely characterized and have yet to be validated in large cohorts. By analyzing longitudinal tumor biopsies from 17 metastatic melanoma patients treated with CPB therapies, we observed point mutations, deletions or loss of heterozygosity (LOH) in beta-2-microglobulin (B2M), an essential component of MHC class I antigen presentation, in 29.4% of patients with progressing disease. In two independent cohorts of melanoma patients treated with anti-CTLA4 and anti-PD1, respectively, we find that B2M LOH is enriched threefold in non-responders (~30%) compared to responders (~10%) and associated with poorer overall survival. Loss of both copies of B2M is found only in non-responders. B2M loss is likely a common mechanism of resistance to therapies targeting CTLA4 or PD1.

  19. Identification of a novel EGF-sensitive cell cycle checkpoint

    International Nuclear Information System (INIS)

    Walker, Francesca; Zhang Huihua; Burgess, Antony W.

    2007-01-01

    The site of action of growth factors on mammalian cell cycle has been assigned to the boundary between the G1 and S phases. We show here that Epidermal Growth Factor (EGF) is also required for mitosis. BaF/3 cells expressing the EGFR (BaF/wtEGFR) synthesize DNA in response to EGF, but arrest in S-phase. We have generated a cell line (BaF/ERX) with defective downregulation of the EGFR and sustained activation of EGFR signalling pathways: these cells undergo mitosis in an EGF-dependent manner. The transit of BaF/ERX cells through G2/M strictly requires activation of EGFR and is abolished by AG1478. This phenotype is mimicked by co-expression of ErbB2 in BaF/wtEGFR cells, and abolished by inhibition of the EGFR kinase, suggesting that sustained signalling of the EGFR, through impaired downregulation of the EGFR or heterodimerization, is required for completion of the cycle. We have confirmed the role of EGFR signalling in the G2/M phase of the cell cycle using a human tumor cell line which overexpresses the EGFR and is dependent on EGFR signalling for growth. These findings unmask an EGF-sensitive checkpoint, helping to understand the link between sustained EGFR signalling, proliferation and the acquisition of a radioresistant phenotype in cancer cells

  20. Loss of the Greatwall Kinase Weakens the Spindle Assembly Checkpoint.

    Directory of Open Access Journals (Sweden)

    M Kasim Diril

    2016-09-01

    Full Text Available The Greatwall kinase/Mastl is an essential gene that indirectly inhibits the phosphatase activity toward mitotic Cdk1 substrates. Here we show that although Mastl knockout (MastlNULL MEFs enter mitosis, they progress through mitosis without completing cytokinesis despite the presence of misaligned chromosomes, which causes chromosome segregation defects. Furthermore, we uncover the requirement of Mastl for robust spindle assembly checkpoint (SAC maintenance since the duration of mitotic arrest caused by microtubule poisons in MastlNULL MEFs is shortened, which correlates with premature disappearance of the essential SAC protein Mad1 at the kinetochores. Notably, MastlNULL MEFs display reduced phosphorylation of a number of proteins in mitosis, which include the essential SAC kinase MPS1. We further demonstrate that Mastl is required for multi-site phosphorylation of MPS1 as well as robust MPS1 kinase activity in mitosis. In contrast, treatment of MastlNULL cells with the phosphatase inhibitor okadaic acid (OKA rescues the defects in MPS1 kinase activity, mislocalization of phospho-MPS1 as well as Mad1 at the kinetochore, and premature SAC silencing. Moreover, using in vitro dephosphorylation assays, we demonstrate that Mastl promotes persistent MPS1 phosphorylation by inhibiting PP2A/B55-mediated MPS1 dephosphorylation rather than affecting Cdk1 kinase activity. Our findings establish a key regulatory function of the Greatwall kinase/Mastl->PP2A/B55 pathway in preventing premature SAC silencing.

  1. Loss of the Greatwall Kinase Weakens the Spindle Assembly Checkpoint.

    Science.gov (United States)

    Diril, M Kasim; Bisteau, Xavier; Kitagawa, Mayumi; Caldez, Matias J; Wee, Sheena; Gunaratne, Jayantha; Lee, Sang Hyun; Kaldis, Philipp

    2016-09-01

    The Greatwall kinase/Mastl is an essential gene that indirectly inhibits the phosphatase activity toward mitotic Cdk1 substrates. Here we show that although Mastl knockout (MastlNULL) MEFs enter mitosis, they progress through mitosis without completing cytokinesis despite the presence of misaligned chromosomes, which causes chromosome segregation defects. Furthermore, we uncover the requirement of Mastl for robust spindle assembly checkpoint (SAC) maintenance since the duration of mitotic arrest caused by microtubule poisons in MastlNULL MEFs is shortened, which correlates with premature disappearance of the essential SAC protein Mad1 at the kinetochores. Notably, MastlNULL MEFs display reduced phosphorylation of a number of proteins in mitosis, which include the essential SAC kinase MPS1. We further demonstrate that Mastl is required for multi-site phosphorylation of MPS1 as well as robust MPS1 kinase activity in mitosis. In contrast, treatment of MastlNULL cells with the phosphatase inhibitor okadaic acid (OKA) rescues the defects in MPS1 kinase activity, mislocalization of phospho-MPS1 as well as Mad1 at the kinetochore, and premature SAC silencing. Moreover, using in vitro dephosphorylation assays, we demonstrate that Mastl promotes persistent MPS1 phosphorylation by inhibiting PP2A/B55-mediated MPS1 dephosphorylation rather than affecting Cdk1 kinase activity. Our findings establish a key regulatory function of the Greatwall kinase/Mastl->PP2A/B55 pathway in preventing premature SAC silencing.

  2. Is the New Immigration Really So Bad?

    OpenAIRE

    Card, David Edward

    2004-01-01

    This paper reviews the recent evidence on U.S. immigration, focusing on two key questions: (1) Does immigration reduce the labor market opportunities of less-skilled natives? (2) Have immigrants who arrived after the 1965 Immigration Reform Act successfully assimilated? Looking across major cities, differential immigrant inflows are strongly correlated with the relative supply of high school dropouts. Nevertheless, data from the 2000 Census shows that relative wages of native dropouts are unc...

  3. Immigrant Workers and Farm Performance

    DEFF Research Database (Denmark)

    Malchow-Møller, Nikolaj; Munch, Jakob R.; Seidelin, Claus Aastrup

    2013-01-01

    for Danish farms in 1980–2008 to analyze the micro-level relationship between these two developments. Farms employing immigrants tend to be both larger than and no less productive than other farms. Furthermore, an increased use of immigrants is associated with an improvement in job creation and revenue......In many developed countries, the agricultural sector has experienced a significant inflow of immigrants. At the same time, agriculture is still in a process of structural transformation, resulting in fewer but larger and presumably more efficient farms. We exploit matched employer-employee data...

  4. Immigrants' language skills: the immigrant experience in a longitudinal survey

    OpenAIRE

    Barry CHISWICK; Yew LEE; Paul W. MILLER

    2003-01-01

    This paper is concerned with the determinants of English language proficiency among immigrants. It presents a model based on economic incentives, exposure, and efficiency in language acquisition, which it tests using the Longitudinal Survey of Immigrants to Australia. Probit and bivariate probit analyses are employed. The hypotheses are supported by the data. The bivariate probit analysis across waves indicates a "regression to the mean" in the unobserved components of English language profic...

  5. Smurf2 as a novel mitotic regulator: From the spindle assembly checkpoint to tumorigenesis

    Directory of Open Access Journals (Sweden)

    Moore Finola E

    2009-07-01

    Full Text Available Abstract The execution of the mitotic program with high fidelity is dependent upon precise spatiotemporal regulation of posttranslational protein modifications. For example, the timely polyubiquitination of critical mitotic regulators by Anaphase Promoting Complex/Cyclosome (APC/C is essential for the metaphase to anaphase transition and mitotic exit. The spindle assembly checkpoint prevents unscheduled activity of APC/C-Cdc20 in early mitosis, allowing bipolar attachment of kinetochores to mitotic spindle and facilitating equal segregation of sister chromatids. The critical effector of the spindle checkpoint, Mitotic arrest deficient 2 (Mad2, is recruited to unattached kinetochores forming a complex with other regulatory proteins to efficiently and cooperatively inhibit APC/C-Cdc20. A weakened and/or dysfunctional spindle checkpoint has been linked to the development of genomic instability in both cell culture and animal models, and evidence suggests that aberrant regulation of the spindle checkpoint plays a critical role in human carcinogenesis. Recent studies have illuminated a network of both degradative and non-degradative ubiquitination events that regulate the metaphase to anaphase transition and mitotic exit. Within this context, our recent work showed that the HECT (Homologous to E6-AP C-terminus-family E3 ligase Smurf2 (Smad specific ubiquitin regulatory factor 2, known as a negative regulator of transforming growth factor-beta (TGF-β signaling, is required for a functional spindle checkpoint by promoting the functional localization and stability of Mad2. Here we discuss putative models explaining the role of Smurf2 as a new regulator in the spindle checkpoint. The dynamic mitotic localization of Smurf2 to the centrosome and other critical mitotic structures provides implications about mitotic checkpoint control dependent on various ubiquitination events. Finally, deregulated Smurf2 activity may contribute to carcinogenesis by

  6. Bir1 Deletion Causes Malfunction of the Spindle Assembly Checkpoint and Apoptosis in Yeast

    International Nuclear Information System (INIS)

    Ren, Qun; Liou, Liang-Chun; Gao, Qiuqiang; Bao, Xiaoming; Zhang, Zhaojie

    2012-01-01

    Cell division in yeast is a highly regulated and well studied event. Various checkpoints are placed throughout the cell cycle to ensure faithful segregation of sister chromatids. Unexpected events, such as DNA damage or oxidative stress, cause the activation of checkpoint(s) and cell cycle arrest. Malfunction of the checkpoints may induce cell death. We previously showed that under oxidative stress, the budding yeast cohesin Mcd1, a homolog of human Rad21, was cleaved by the caspase-like protease Esp1. The cleaved Mcd1 C-terminal fragment was then translocated to mitochondria, causing apoptotic cell death. In the present study, we demonstrated that Bir1 plays an important role in spindle assembly checkpoint and cell death. Similar to H 2 O 2 treatment, deletion of BIR1 using a BIR1-degron strain caused degradation of the securin Pds1, which binds and inactivates Esp1 until metaphase-anaphase transition in a normal cell cycle. BIR1 deletion caused an increase level of ROS and mis-location of Bub1, a major protein for spindle assembly checkpoint. In wild type, Bub1 was located at the kinetochores, but was primarily in the cytoplasm in bir1 deletion strain. When BIR1 was deleted, addition of nocodazole was unable to retain the Bub1 localization on kinetochores, further suggesting that Bir1 is required to activate and maintain the spindle assembly checkpoint. Our study suggests that the BIR1 function in cell cycle regulation works in concert with its anti-apoptosis function.

  7. Attitudes toward unauthorized immigrants, authorized immigrants, and refugees.

    Science.gov (United States)

    Murray, Kate E; Marx, David M

    2013-07-01

    Rates of human migration are steadily rising and have resulted in significant sociopolitical debates over how to best respond to increasing cultural diversity and changing migration patterns. Research on prejudicial attitudes toward immigrants has focused on the attitudes and beliefs that individuals in the receiving country hold about immigrants. The current study enhances this literature by examining how young adults view authorized and unauthorized immigrants and refugees. Using a between-groups design of 191 undergraduates, we found that participants consistently reported more prejudicial attitudes, greater perceived realistic threats, and greater intergroup anxiety when responding to questions about unauthorized compared with authorized immigrants. Additionally, there were differences in attitudes depending on participants' generational status, with older-generation participants reporting greater perceived realistic and symbolic threat, prejudice, and anxiety than newer-generation students. In some instances, these effects were moderated by participant race/ethnicity and whether they were evaluating authorized or unauthorized immigrants. Lastly, perceived realistic threat, symbolic threat, and intergroup anxiety were significant predictors of prejudicial attitudes. Overall, participants reported positive attitudes toward refugees and resettlement programs in the United States. These findings have implications for future research and interventions focused on immigration and prejudice toward migrant groups. PsycINFO Database Record (c) 2013 APA, all rights reserved.

  8. The amount of DNA damage needed to activate the radiation-induced G2 checkpoint varies between single cells

    International Nuclear Information System (INIS)

    Tkacz-Stachowska, Kinga; Lund-Andersen, Christin; Velissarou, Angeliki; Myklebust, June H.; Stokke, Trond; Syljuåsen, Randi G.

    2011-01-01

    Background and purpose: The radiation-induced G2 checkpoint helps facilitate DNA repair before cell division. However, recent work has revealed that human cells often escape the G2 checkpoint with unrepaired DNA breaks. The purpose was to explore whether G2 checkpoint activation occurs according to a threshold level of DNA damage. Materials and methods: G2 checkpoint activation was assayed at 75–90 min and 24–48 h after X-ray irradiation of BJ diploid fibroblasts and U2OS osteosarcoma cells. Multiparameter flow cytometry with pacific blue barcoding, and flow cytometry-based sorting of phospho-H3 positive cells to microscope slides, were used to examine the DNA damage marker γ-H2AX in individual mitotic cells that had escaped the G2 checkpoint. Results: For all radiation doses and times tested, the number of γ-H2AX foci varied between individual mitotic cells. At 75 min the median levels of γ-H2AX in mitotic cells increased with higher radiation doses. At 24–48 h, following a prolonged G2 checkpoint, cells were more resistant to checkpoint re-activation by a second dose of radiation. Conclusion: Our results suggest that different amounts of DNA damage are needed to activate the G2 checkpoint in individual cells. Such single cell variation in checkpoint activation may potentially contribute to radiation-induced genomic instability.

  9. Asynchronous Two-Level Checkpointing Scheme for Large-Scale Adjoints in the Spectral-Element Solver Nek5000

    Energy Technology Data Exchange (ETDEWEB)

    Schanen, Michel; Marin, Oana; Zhang, Hong; Anitescu, Mihai

    2016-01-01

    Adjoints are an important computational tool for large-scale sensitivity evaluation, uncertainty quantification, and derivative-based optimization. An essential component of their performance is the storage/recomputation balance in which efficient checkpointing methods play a key role. We introduce a novel asynchronous two-level adjoint checkpointing scheme for multistep numerical time discretizations targeted at large-scale numerical simulations. The checkpointing scheme combines bandwidth-limited disk checkpointing and binomial memory checkpointing. Based on assumptions about the target petascale systems, which we later demonstrate to be realistic on the IBM Blue Gene/Q system Mira, we create a model of the expected performance of our checkpointing approach and validate it using the highly scalable Navier-Stokes spectralelement solver Nek5000 on small to moderate subsystems of the Mira supercomputer. In turn, this allows us to predict optimal algorithmic choices when using all of Mira. We also demonstrate that two-level checkpointing is significantly superior to single-level checkpointing when adjoining a large number of time integration steps. To our knowledge, this is the first time two-level checkpointing had been designed, implemented, tuned, and demonstrated on fluid dynamics codes at large scale of 50k+ cores.

  10. Casein kinase II is required for the spindle assembly checkpoint by regulating Mad2p in fission yeast

    International Nuclear Information System (INIS)

    Shimada, Midori; Yamamoto, Ayumu; Murakami-Tonami, Yuko; Nakanishi, Makoto; Yoshida, Takashi; Aiba, Hirofumi; Murakami, Hiroshi

    2009-01-01

    The spindle checkpoint is a surveillance mechanism that ensures the fidelity of chromosome segregation in mitosis. Here we show that fission yeast casein kinase II (CK2) is required for this checkpoint function. In the CK2 mutants mitosis occurs in the presence of a spindle defect, and the spindle checkpoint protein Mad2p fails to localize to unattached kinetochores. The CK2 mutants are sensitive to the microtubule depolymerising drug thiabendazole, which is counteracted by ectopic expression of mad2 + . The level of Mad2p is low in the CK2 mutants. These results suggest that CK2 has a role in the spindle checkpoint by regulating Mad2p.

  11. Mathematics Achievement by Immigrant Children

    Directory of Open Access Journals (Sweden)

    Gary G. Huang

    2000-05-01

    Full Text Available In this study, I examined academic achievement of immigrant children in the United States, Canada, England, Australia, and New Zealand. Analyzing data from the Third International Mathematics and Science Study (TIMSS, I gauged the performance gaps relating to the generation of immigration and the home language background. I found immigrant children's math and science achievement to be lower than the others only in England, the U.S., and Canada. Non-English language background was found in each country to relate to poor math and science learning and this disadvantage was stronger among native-born children—presumably children of indigenous groups—than among immigrant children. I also examined the school variation in math performance gaps, using hierarchical linear modeling (HLM to each country's data. The patterns in which language- and generation-related math achievement gaps varied between schools are different in the five countries.

  12. In-silico modeling of the mitotic spindle assembly checkpoint.

    Directory of Open Access Journals (Sweden)

    Bashar Ibrahim

    2008-02-01

    Full Text Available The Mitotic Spindle Assembly Checkpoint ((MSAC is an evolutionary conserved mechanism that ensures the correct segregation of chromosomes by restraining cell cycle progression from entering anaphase until all chromosomes have made proper bipolar attachments to the mitotic spindle. Its malfunction can lead to cancer.We have constructed and validated for the human (MSAC mechanism an in silico dynamical model, integrating 11 proteins and complexes. The model incorporates the perspectives of three central control pathways, namely Mad1/Mad2 induced Cdc20 sequestering based on the Template Model, MCC formation, and APC inhibition. Originating from the biochemical reactions for the underlying molecular processes, non-linear ordinary differential equations for the concentrations of 11 proteins and complexes of the (MSAC are derived. Most of the kinetic constants are taken from literature, the remaining four unknown parameters are derived by an evolutionary optimization procedure for an objective function describing the dynamics of the APC:Cdc20 complex. MCC:APC dissociation is described by two alternatives, namely the "Dissociation" and the "Convey" model variants. The attachment of the kinetochore to microtubuli is simulated by a switching parameter silencing those reactions which are stopped by the attachment. For both, the Dissociation and the Convey variants, we compare two different scenarios concerning the microtubule attachment dependent control of the dissociation reaction. Our model is validated by simulation of ten perturbation experiments.Only in the controlled case, our models show (MSAC behaviour at meta- to anaphase transition in agreement with experimental observations. Our simulations revealed that for (MSAC activation, Cdc20 is not fully sequestered; instead APC is inhibited by MCC binding.

  13. Acute symptomatic hypocalcemia from immune checkpoint therapy-induced hypoparathyroidism.

    Science.gov (United States)

    Win, Myint Aung; Thein, Kyaw Zin; Qdaisat, Aiham; Yeung, Sai-Ching Jim

    2017-07-01

    Ipilimumab (a monoclonal antibody against CTLA-4) and nivolumab (a humanized antibody against PD-1) target these immune checkpoint pathways and are used for treatment of melanoma and an increasing number of other cancers. However, they may cause immune-related adverse effects (IRAEs). Although many endocrinopathies are known to be IRAEs, primary hypoparathyroidism with severe hypocalcemia has never been reported. This is the first case of hypoparathyroidism as an IRAE presenting to an Emergency Department with acute hypocalcemia. A 73-year-old man with metastatic melanoma presented to the Emergency Department for the chief complaints of imbalance, general muscle weakness, abdominal pain and tingling in extremities. He had wide spread metastasis, and begun immunotherapy with concurrent ipilimumab and nivolumab 1.5months ago. At presentation, he had ataxia, paresthesia in the hands and feet, and abdominal cramping. Magnetic resonance imaging of the brain was unremarkable. He was found to be hypocalcemic with undetectable plasma parathyroid hormone. He was admitted for treatment of symptomatic hypocalcemia and was diagnosed with primary hypoparathyroidism. Shortly afterwards, he had thyrotoxicosis manifesting as tachycardia and anxiety, followed by development of primary hypothyroidism. At 4months after the Emergency Department visit, his parathyroid function and thyroid function had not recovered, and required continued thyroid hormone replacement and calcium and vitamin D treatment for hypocalcemia. Primary hypoparathyroidism caused by ipilimumab and nivolumab may acute manifest with severe symptomatic hypocalcemia. Emergency care providers should be aware of hypoparathyroidism as a new IRAE in this new era of immuno-oncology. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Calreticulin reveals a critical Ca2+ checkpoint in cardiac myofibrillogenesis

    Science.gov (United States)

    Li, Jian; Pucéat, Michel; Perez-Terzic, Carmen; Mery, Annabelle; Nakamura, Kimitoshi; Michalak, Marek; Krause, Karl-Heinz; Jaconi, Marisa E.

    2002-01-01

    Calreticulin (crt) is an ubiquitously expressed and multifunctional Ca2+-binding protein that regulates diverse vital cell functions, including Ca2+ storage in the ER and protein folding. Calreticulin deficiency in mice is lethal in utero due to defects in heart development and function. Herein, we used crt − / − embryonic stem (ES) cells differentiated in vitro into cardiac cells to investigate the molecular mechanisms underlying heart failure of knockout embryos. After 8 d of differentiation, beating areas were prominent in ES-derived wild-type (wt) embryoid bodies (EBs), but not in ES-derived crt − / − EBs, despite normal expression levels of cardiac transcription factors. Crt − / − EBs exhibited a severe decrease in expression and a lack of phosphorylation of ventricular myosin light chain 2 (MLC2v), resulting in an impaired organization of myofibrils. Crt − / − phenotype could be recreated in wt cells by chelating extracellular or cytoplasmic Ca2+ with EGTA or BAPTA, or by inhibiting Ca2+/calmodulin-dependent kinases (CaMKs). An imposed ionomycin-triggered cystolic-free Ca2+ concentration ([Ca2+]c) elevation restored the expression, phosphorylation, and insertion of MLC2v into sarcomeric structures and in turn the myofibrillogenesis. The transcription factor myocyte enhancer factor C2 failed to accumulate into nuclei of crt − / − cardiac cells in the absence of ionomycin-triggered [Ca2+]c increase. We conclude that the absence of calreticulin interferes with myofibril formation. Most importantly, calreticulin deficiency revealed the importance of a Ca2+-dependent checkpoint critical for early events during cardiac myofibrillogenesis. PMID:12105184

  15. Immigrant Women and Partner Violence

    OpenAIRE

    KUUSELA, HANNA

    2011-01-01

    Violence against women is a global problem, which can be recognized in every society and culture. Both in Canada and Finland the research about violence against immigrant women has begun quite recently and therefore, there is still a lot we do not know about this phenomenon and thus a demand for research. Immigrant women face unique circumstances and are in a vulnerable position of being abused. They are not a homogeneous group, on the contrary, they have individual life experiences but they ...

  16. Immigrant Entrepreneurs, Diasporas and Exports

    OpenAIRE

    Bratti, Massimiliano; De Benedictis, Luca; Santoni, Gianluca

    2018-01-01

    In this paper we highlight a new complementary channel to the business and social network effect à la Rauch (2001) through which immigrants generate increased export flows from the regions in which they settle to their countries of origin: they can become entrepreneurs. Using very small-scale (NUTS-3) administrative data on immigrants’ location in Italy, the local presence of immigrant entrepreneurs (i.e. firms owned by foreign-born entrepreneurs) in the manufacturing sector, and on trade ...

  17. Immigration, Wages, and Compositional Amenities

    OpenAIRE

    David Card; Christian Dustmann; Ian Preston

    2009-01-01

    Economists are often puzzled by the stronger public opposition to immigration than trade, since the two policies have symmetric effects on wages. Unlike trade, however, immigration changes the composition of the local population, imposing potential externalities on natives. While previous studies have focused on fiscal spillovers, a broader class of externalities arise because people value the "compositional amenities" associated with the characteristics of their neighbors and co-workers. In ...

  18. Chinese Immigrant Wealth: Heterogeneity in Adaptation

    Science.gov (United States)

    Agius Vallejo, Jody; Aronson, Brian

    2016-01-01

    Chinese immigrants are a diverse and growing group whose members provide a unique opportunity to examine within-immigrant group differences in adaptation. In this paper, we move beyond thinking of national-origin groups as homogenous and study variation among Chinese immigrants in wealth ownership, a critical indicator of adaptation that attracts relatively little attention in the immigration literature. We develop an analytical approach that considers national origin, tenure in the U.S., and age to examine heterogeneity in economic adaptation among the immigrant generation. Our results show that variations among Chinese immigrants explain within-group differences in net worth, asset ownership, and debt. These differences also account for important variation between Chinese immigrants, natives, and other immigrant groups and provide important, new insight into the processes that lead to immigrant adaptation and long-term class stability. PMID:27977737

  19. Chinese Immigrant Wealth: Heterogeneity in Adaptation.

    Science.gov (United States)

    Keister, Lisa A; Agius Vallejo, Jody; Aronson, Brian

    2016-01-01

    Chinese immigrants are a diverse and growing group whose members provide a unique opportunity to examine within-immigrant group differences in adaptation. In this paper, we move beyond thinking of national-origin groups as homogenous and study variation among Chinese immigrants in wealth ownership, a critical indicator of adaptation that attracts relatively little attention in the immigration literature. We develop an analytical approach that considers national origin, tenure in the U.S., and age to examine heterogeneity in economic adaptation among the immigrant generation. Our results show that variations among Chinese immigrants explain within-group differences in net worth, asset ownership, and debt. These differences also account for important variation between Chinese immigrants, natives, and other immigrant groups and provide important, new insight into the processes that lead to immigrant adaptation and long-term class stability.

  20. Chinese Immigrant Wealth: Heterogeneity in Adaptation.

    Directory of Open Access Journals (Sweden)

    Lisa A Keister

    Full Text Available Chinese immigrants are a diverse and growing group whose members provide a unique opportunity to examine within-immigrant group differences in adaptation. In this paper, we move beyond thinking of national-origin groups as homogenous and study variation among Chinese immigrants in wealth ownership, a critical indicator of adaptation that attracts relatively little attention in the immigration literature. We develop an analytical approach that considers national origin, tenure in the U.S., and age to examine heterogeneity in economic adaptation among the immigrant generation. Our results show that variations among Chinese immigrants explain within-group differences in net worth, asset ownership, and debt. These differences also account for important variation between Chinese immigrants, natives, and other immigrant groups and provide important, new insight into the processes that lead to immigrant adaptation and long-term class stability.

  1. Caffeine stabilizes Cdc25 independently of Rad3 in S chizosaccharomyces pombe contributing to checkpoint override

    Science.gov (United States)

    Alao, John P; Sjölander, Johanna J; Baar, Juliane; Özbaki-Yagan, Nejla; Kakoschky, Bianca; Sunnerhagen, Per

    2014-01-01

    Cdc25 is required for Cdc2 dephosphorylation and is thus essential for cell cycle progression. Checkpoint activation requires dual inhibition of Cdc25 and Cdc2 in a Rad3-dependent manner. Caffeine is believed to override activation of the replication and DNA damage checkpoints by inhibiting Rad3-related proteins in both S chizosaccharomyces pombe and mammalian cells. In this study, we have investigated the impact of caffeine on Cdc25 stability, cell cycle progression and checkpoint override. Caffeine induced Cdc25 accumulation in S . pombe independently of Rad3. Caffeine delayed cell cycle progression under normal conditions but advanced mitosis in cells treated with replication inhibitors and DNA-damaging agents. In the absence of Cdc25, caffeine inhibited cell cycle progression even in the presence of hydroxyurea or phleomycin. Caffeine induces Cdc25 accumulation in S . pombe by suppressing its degradation independently of Rad3. The induction of Cdc25 accumulation was not associated with accelerated progression through mitosis, but rather with delayed progression through cytokinesis. Caffeine-induced Cdc25 accumulation appears to underlie its ability to override cell cycle checkpoints. The impact of Cdc25 accumulation on cell cycle progression is attenuated by Srk1 and Mad2. Together our findings suggest that caffeine overrides checkpoint enforcement by inducing the inappropriate nuclear localization of Cdc25. PMID:24666325

  2. Checkpoint inhibitors in advanced melanoma: effect on the field of immunotherapy.

    Science.gov (United States)

    O'reilly, Aine; Larkin, James

    2017-07-01

    The success of the immune checkpoint inhibitors in melanoma has reinvigorated the field of immunotherapy. Immune checkpoint inhibitors are now the standard of care in multiple cancer types including lung cancer, head and neck cancer, urothelial cancer and renal cell cancer. The field of immunotherapy is currently expanding rapidly and will be a focus of research and development for decades to come. Areas covered: This review covers the early development of immune checkpoint inhibitors and the changes that occurred in the drug development paradigm to facilitate the development of immunotherapy. The review will summarise the areas into which immune checkpoint inhibitors have been adopted and will review the data that supported this. Furthermore, we will discuss future developments in immunotherapy and the current landscape regarding maximising the potential of immunotherapy in clinical practice. Expert commentary: In the author's opinion, the potential of immunotherapy is vast. To date immune checkpoint inhibition has already delivered durable responses in a proportion of patients with cancer types which were previously universally lethal. The future of immunotherapy will rely upon the intelligent application of translational research to clinical practice, such that immunotherapy can be effective for a wider population and maintain its current growth.

  3. Different paths: gender, immigration and political participation.

    Science.gov (United States)

    Jones-correa, M

    1998-01-01

    "Building on arguments made by Grasmuck and Pessar (1991), Hardy-Fanta (1993), and Hondagneu-Sotelo (1994), among others, this article makes the case for a gendered understanding of immigrant political socialization. Looking at recent Latin American immigrants to New York City, the article argues that immigrant Latino men are more likely to favor continuity in patterns of socialization and organization, and immigrant Latinas are more likely to favor change. This finding helps bridge theoretical and empirical literatures in immigration studies, applying the logic of gender-differentiated decisionmaking to the area of immigrant political socialization and behavior." excerpt

  4. Immigration Ethnic Diversity and Political Outcomes

    DEFF Research Database (Denmark)

    Harmon, Nikolaj Arpe

    2017-01-01

    I study the impact of immigration and increasing ethnic diversity on political outcomes in immigrant-receiving countries, focusing on immigration and election outcomes in Danish municipalities 1981-2001. A rich set of control variables isolates ethnic diversity effects from those of other immigrant...... characteristics and a novel IV strategy based on historical housing stock data addresses issues of endogenous location choices of immigrants. Increases in local ethnic diversity lead to right-ward shifts in election outcomes by shifting electoral support away from traditional "big government" left-wing parties...... and towards anti-immigrant nationalist parties in particular. These effects appear in both local and national elections....

  5. Labour Market Interactions Between Legal and Illegal Immigrants

    OpenAIRE

    Epstein, Gil S

    2000-01-01

    This paper looks at the situation of legal immigrants who employ illegal immigrants to provide them with various services. This enables the legal immigrants to allocate more time to other work, thereby increasing their earnings. Illegal immigrants employed by legal immigrants may specialize in certain professions and may themselves employ other illegal immigrants. An economy is evolving whose sole purpose is the provision of services by illegal immigrants for legal immigrants.

  6. Labor Market Interactions Between Legal and Illegal Immigrants

    OpenAIRE

    Epstein, Gil S.

    2000-01-01

    This paper looks at the situation of legal immigrants who employ illegal immigrants to provide them with various services. This enables the legal immigrants to allocate more time to other work, thereby increasing their earnings. Illegal immigrants employed by legal immigrants may specialize in certain professions and may themselves employ other illegal immigrants. An economy is evolving whose sole purpose is the provision of services by illegal immigrants for legal immigrants.

  7. Asian Immigration: The View from the United States.

    Science.gov (United States)

    Gardner, Robert W.

    1992-01-01

    Examines contemporary Asian immigration to the United States from a U.S. perspective. Analyzes immigration policies and data on recent immigration from Asia. Discusses impacts concerning the United States and the immigrants themselves and speculates on future immigration. The composition of Asian immigration might change, and the number might…

  8. Beyond CTLA-4 and PD-1, the generation Z of negative checkpoint regulators.

    Directory of Open Access Journals (Sweden)

    Isabelle eLe Mercier

    2015-08-01

    Full Text Available In the last two years, clinical trials with blocking antibodies to the negative checkpoint regulators CTLA-4 and PD-1 have rekindled the hope for cancer immunotherapy. Multiple negative checkpoint regulators protect the host against autoimmune reactions but also restrict the ability of T cells to effectively attack tumors. Releasing these brakes has emerged as an exciting strategy for cancer treatment. Conversely, these pathways can be manipulated to achieve durable tolerance for treatment of autoimmune diseases and transplantation. In the future, treatment may involve combination therapy to target multiple cell types and stages of the adaptive immune responses. In this review, we describe the current knowledge on the recently discovered negative checkpoint regulators, future targets for immunotherapy.

  9. Beyond CTLA-4 and PD-1, the Generation Z of Negative Checkpoint Regulators.

    Science.gov (United States)

    Le Mercier, Isabelle; Lines, J Louise; Noelle, Randolph J

    2015-01-01

    In the last two years, clinical trials with blocking antibodies to the negative checkpoint regulators CTLA-4 and PD-1 have rekindled the hope for cancer immunotherapy. Multiple negative checkpoint regulators protect the host against autoimmune reactions but also restrict the ability of T cells to effectively attack tumors. Releasing these brakes has emerged as an exciting strategy for cancer treatment. Conversely, these pathways can be manipulated to achieve durable tolerance for treatment of autoimmune diseases and transplantation. In the future, treatment may involve combination therapy to target multiple cell types and stages of the adaptive immune responses. In this review, we describe the current knowledge on the recently discovered negative checkpoint regulators, future targets for immunotherapy.

  10. Blocking CHK1 Expression Induces Apoptosis and Abrogates the G2 Checkpoint Mechanism

    Directory of Open Access Journals (Sweden)

    Yan Luo

    2001-01-01

    Full Text Available Checkpoint kinase 1 (Chki is a checkpoint gene that is activated after DNA damage. It phosphorylates and inactivates the Cdc2 activating phosphatase Cdc25C. This in turn inactivates Cdc2, which leads to G2/M arrest. We report that blocking Chki expression by antisense or ribozymes in mammalian cells induces apoptosis and interferes with the G2/M arrest induced by adriamycin. The Chki inhibitor UCN-01 also blocks the G2 arrest after DNA damage and renders cells more susceptible to adriamycin. These results indicate that Chki is an essential gene for the checkpoint mechanism during normal cell proliferation as well as in the DNA damage response.

  11. A tumor suppressor role of the Bub3 spindle checkpoint protein after apoptosis inhibition

    Science.gov (United States)

    Moutinho-Santos, Tatiana

    2013-01-01

    Most solid tumors contain aneuploid cells, indicating that the mitotic checkpoint is permissive to the proliferation of chromosomally aberrant cells. However, mutated or altered expression of mitotic checkpoint genes accounts for a minor proportion of human tumors. We describe a Drosophila melanogaster tumorigenesis model derived from knocking down spindle assembly checkpoint (SAC) genes and preventing apoptosis in wing imaginal discs. Bub3-deficient tumors that were also deficient in apoptosis displayed neoplastic growth, chromosomal aneuploidy, and high proliferative potential after transplantation into adult flies. Inducing aneuploidy by knocking down CENP-E and preventing apoptosis does not induce tumorigenesis, indicating that aneuploidy is not sufficient for hyperplasia. In this system, the aneuploidy caused by a deficient SAC is not driving tumorigenesis because preventing Bub3 from binding to the kinetochore does not cause hyperproliferation. Our data suggest that Bub3 has a nonkinetochore-dependent function that is consistent with its role as a tumor suppressor. PMID:23609535

  12. Hospitalisation among immigrants in Italy

    Directory of Open Access Journals (Sweden)

    Geraci Salvatore

    2006-05-01

    Full Text Available Abstract Background Immigration is increasing in Italy. In 2003, 2.6 million foreign citizens lived in the country; 52% were men and the majority were young adults who migrated for work. The purpose of this study was to investigate differences in hospitalisation between immigrants and the resident population during the year 2000 in the Lazio region. Methods Hospital admissions of immigrants from Less Developed Countries were compared to those of residents. We measured differences in hospitalisation rates and proportions admitted. Results Adult immigrants have lower hospitalisation rates than residents (134.6 vs. 160.5 per thousand population for acute care; 26.4 vs. 38.3 for day care. However, hospitalisation rates for some specific causes (injuries, particularly for men, infectious diseases, deliveries and induced abortions, ill-defined conditions were higher for immigrants than for residents. Immigrants under 18 years seem to be generally healthy; causes of admission in this group are similar to those of residents of the same age (respiratory diseases, injuries and poisoning. The only important differences are for infectious and parasitic diseases, with a higher proportion among immigrant youths. Conclusion The low hospitalisation rates for foreigners may suggest that they are a population with good health status. However, critical areas, related to poor living and working conditions and to social vulnerability, have been identified. Under-utilisation of services and low day care rates may be partially due to administrative, linguistic, and cultural barriers. As the presence of foreigners becomes an established phenomenon, it is important to evaluate their epidemiological profile, develop instruments to monitor and fulfil their specific health needs and plan health services for a multi-ethnic population.

  13. 78 FR 31398 - Visas: Documentation of Immigrants Under the Immigration and Nationality Act, as Amended

    Science.gov (United States)

    2013-05-24

    ... Immigrants Under the Immigration and Nationality Act, as Amended AGENCY: Department of State. ACTION: Final... method of recording an alien's entitlement to an immigrant visa classification. Due to the availability of automated systems at all immigrant visa-issuing posts, this entitlement is now recorded...

  14. The anaphase inhibitor of Saccharomyces cerevisiae Pds1p is a target of the DNA damage checkpoint pathway

    International Nuclear Information System (INIS)

    Cohen-Fix, O.; Koshland, D.

    1997-01-01

    Inhibition of DNA replication and physical DNA damage induce checkpoint responses that arrest cell cycle progression at two different stages. In Saccharomyces cerevisiae, the execution of both checkpoint responses requires the Mec1 and Rad53 proteins. This observation led to the suggestion that these checkpoint responses are mediated through a common signal transduction pathway. However, because the checkpoint-induced arrests occur at different cell cycle stages, the downstream effectors mediating these arrests are likely to be distinct. We have previously shown that the S. cerevisiae protein Pds1p is an anaphase inhibitor and is essential for cell cycle arrest in mitosis in the presence DNA damage. Herein we show that DNA damage, but not inhibition of DNA replication, induces the phosphorylation of Pds1p. Analyses of Pds1p phosphorylation in different checkpoint mutants reveal that in the presence of DNA damage, Pds1p is phosphorylated in a Mec1p- and Rad9p-dependent hut Rad53p-independent manner. Our data place Pds1p and Rad53p on parallel branches of the DNA damage checkpoint pathway. We suggest that Pds1p is a downstream target of the DNA damage checkpoint pathway and that it is involved in implementing the DNA damage checkpoint arrest specifically in mitosis

  15. Use of common time base for checkpointing and rollback recovery in a distributed system

    Science.gov (United States)

    Ramanathan, Parameswaran; Shin, Kang G.

    1993-01-01

    An approach to checkpointing and rollback recovery in a distributed computing system using a common time base is proposed. A common time base is established in the system using a hardware clock synchronization algorithm. This common time base is coupled with the idea of pseudo-recovery points to develop a checkpointing algorithm that has the following advantages: reduced wait for commitment for establishing recovery lines, fewer messages to be exchanged, and less memory requirement. These advantages are assessed quantitatively by developing a probabilistic model.

  16. Cyclin F suppresses B-Myb activity to promote cell cycle checkpoint control

    DEFF Research Database (Denmark)

    Klein, Ditte Kjærsgaard; Hoffmann, Saskia; Ahlskog, Johanna K

    2015-01-01

    an important role in checkpoint control following ionizing radiation. Cyclin F-depleted cells initiate checkpoint signalling after ionizing radiation, but fail to maintain G2 phase arrest and progress into mitosis prematurely. Importantly, cyclin F suppresses the B-Myb-driven transcriptional programme...... that promotes accumulation of crucial mitosis-promoting proteins. Cyclin F interacts with B-Myb via the cyclin box domain. This interaction is important to suppress cyclin A-mediated phosphorylation of B-Myb, a key step in B-Myb activation. In summary, we uncover a regulatory mechanism linking the F-box protein...

  17. Interprofessional Collaboration with Immune Checkpoint Inhibitor Therapy: the Roles of Gastroenterology, Endocrinology and Neurology.

    Science.gov (United States)

    Seery, Virginia

    2017-11-01

    To discuss immune checkpoint inhibitor therapy and identify opportunities for interprofessional collaboration in the management of toxicities in the areas of gastroenterology, endocrinology, and neurology. Published research and education articles in oncology, nursing, and various specialties. The use of immune checkpoint inhibitors is expanding; timely management of toxicity is critical for positive patient outcomes. There are many opportunities for interprofessional collaboration in the diagnosis and treatment of immune-related adverse events. Nurses play key roles in recognizing immune-related adverse events, providing patient education, and helping to facilitate interprofessional collaboration. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. U.S. Citizenship and Immigration Services

    Science.gov (United States)

    ... Authorization All USCIS Forms Filing Fees USCIS Electronic Immigration System Order Forms by Mail Order Forms by ... Ask a Question, Get a Trusted Answer Find Immigration Options File Online Manage Your Case Check your ...

  19. The Contributions of Immigrants to American Culture

    OpenAIRE

    Hirschman, Charles

    2013-01-01

    The standard account of American immigration focuses on the acculturation and assimilation of immigrants and their children to American society. This analysis typically ignores the significant contributions of immigrants to the creation of American culture through the performing arts, sciences, and other cultural pursuits. Immigrants and their children are not born with more creative talents than native-born citizens, but their selectivity and marginality may have pushed and pulled those with...

  20. Immigration and the distribution of incomes

    OpenAIRE

    Blau, Francine D.; Kahn, Lawrence M.

    2012-01-01

    We review research on the impact of immigration on income distribution. We discuss routes through which immigration can affect income distribution in the host and source countries, including compositional effects and effects on native incomes. Immigration may affect the composition of skills among the residents of a country. Moreover, immigrants can, by changing relative factor supplies, affect native wage and employment rates and the return to capital. We then provide evidence on the level a...

  1. The Impact of Immigration and Customs Enforcement on Immigrant Health: Perceptions of Immigrants in Everett, Massachusetts, USA

    Science.gov (United States)

    Hacker, Karen; Chu, Jocelyn; Leung, Carolyn; Marra, Robert; Pirie, Alex; Brahimi, Mohamed; English, Margaret; Beckmann, Joshua; Acevedo-Garcia, Dolores; Marlin, Robert P.

    2011-01-01

    U.S. immigrants have faced a changing landscape with regard to immigration enforcement over the last two decades. Following the passage of the Illegal Immigration Reform and Immigrant Responsibility Act of 1996, and the creation of the Immigration and Customs Enforcement (ICE) agency after the attacks of September 11, 2001, detention and deportation activity increased substantially. As a result, immigrants today are experiencing heightened fear of profiling and deportation. Little research exists on how these activities affect the health and well-being of U.S. immigrant communities. This study sought to address this gap by using community-based participatory research to investigate the impact of enhanced immigration enforcement on immigrant health in Everett, Massachusetts, USA, a city with a large and diverse immigrant population. Community partners and researchers conducted 6 focus groups with 52 immigrant participants (documented and undocumented) in five languages in May 2009. The major themes across the groups included: 1) Fear of deportation, 2) Fear of collaboration between local law enforcement and ICE and perception of arbitrariness on the part of the former and 3) Concerns about not being able to furnish documentation required to apply for insurance and for health care. Documented and undocumented immigrants reported high levels of stress due to deportation fear, which affected their emotional well-being and their access to health services. Recommendations from the focus groups included improving relationships between immigrants and local police, educating immigrants on their rights and responsibilities as residents, and holding sessions to improve civic engagement. Immigration enforcement activities and the resulting deportation fear are contextual factors that undermine trust in community institutions and social capital, with implications for health and effective integration processes. These factors should be considered by any community seeking to

  2. The impact of Immigration and Customs Enforcement on immigrant health: perceptions of immigrants in Everett, Massachusetts, USA.

    Science.gov (United States)

    Hacker, Karen; Chu, Jocelyn; Leung, Carolyn; Marra, Robert; Pirie, Alex; Brahimi, Mohamed; English, Margaret; Beckmann, Joshua; Acevedo-Garcia, Dolores; Marlin, Robert P

    2011-08-01

    U.S. immigrants have faced a changing landscape with regard to immigration enforcement over the last two decades. Following the passage of the Illegal Immigration Reform and Immigrant Responsibility Act of 1996, and the creation of the Immigration and Customs Enforcement (ICE) agency after the attacks of September 11, 2001, detention and deportation activity increased substantially. As a result, immigrants today are experiencing heightened fear of profiling and deportation. Little research exists on how these activities affect the health and well-being of U.S. immigrant communities. This study sought to address this gap by using community-based participatory research to investigate the impact of enhanced immigration enforcement on immigrant health in Everett, Massachusetts, USA, a city with a large and diverse immigrant population. Community partners and researchers conducted 6 focus groups with 52 immigrant participants (documented and undocumented) in five languages in May 2009. The major themes across the groups included: 1) Fear of deportation, 2) Fear of collaboration between local law enforcement and ICE and perception of arbitrariness on the part of the former and 3) Concerns about not being able to furnish documentation required to apply for insurance and for health care. Documented and undocumented immigrants reported high levels of stress due to deportation fear, which affected their emotional well-being and their access to health services. Recommendations from the focus groups included improving relationships between immigrants and local police, educating immigrants on their rights and responsibilities as residents, and holding sessions to improve civic engagement. Immigration enforcement activities and the resulting deportation fear are contextual factors that undermine trust in community institutions and social capital, with implications for health and effective integration processes. These factors should be considered by any community seeking to

  3. Immigrants as Portrayed in Children's Picture Books

    Science.gov (United States)

    Lamme, Linda Leonard; Fu, Danling; Lowery, Ruth McKoy

    2004-01-01

    America is a nation of immigrants, many of whom came as part of families, who left their home countries for different reasons to settle here. In the late nineteenth century, immigrants came from Northern Europe and then from Southern Europe, but recent immigrants tend to come from Eastern Europe (mostly old Soviet Union countries), Hispanic, and…

  4. Immigrant Youth Mental Health, Acculturation, and Adaptation

    Science.gov (United States)

    Frabutt, James M.

    2006-01-01

    One in five youth in the United States is a child of an immigrant and children of immigrants are the most rapidly growing segment of the U.S. population under age 18. Consequently, there is a great need to better understand the psychosocial impact of immigration on children's mental health and adjustment. It is striking, however, that research on…

  5. Effectiveness and costeffectiveness of screening immigrants ...

    African Journals Online (AJOL)

    Background: Immigrants to developed countries are a major source of TB. Therefore amongst strategies adopted for TB control in developed countries include; 1) Screening immigrants at ports of entry referred to as “Port of Arrival Screening” (PoA) and 2) Passive screening (PS) for TB which means screening immigrants ...

  6. Immigration, Endogenous Technology Adoption and Wages

    NARCIS (Netherlands)

    Ray Chaudhuri, A.; Pandey, Manish

    2015-01-01

    We document that immigration to U.S. states has increased the mass of workers at the lower range of the skill distribution. We use this change in skill distribution of workers to analyze the effect of immigration on wages. Our model allows firms to endogenously respond to the immigration-induced

  7. 49 CFR 1572.105 - Immigration status.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 9 2010-10-01 2010-10-01 false Immigration status. 1572.105 Section 1572.105... ASSESSMENTS Standards for Security Threat Assessments § 1572.105 Immigration status. (a) An individual... to an order of removal under the immigration laws of the United States is not eligible to apply for a...

  8. Immigration and the transformation of American unionism

    NARCIS (Netherlands)

    Burgoon, B.; Fine, J.; Jacoby, W.; Tichenor, D.

    2010-01-01

    Does immigration hamper union organizing in the United States? The prevailing literature strongly suggests that it does and for two reasons: first, immigrants increase the labor pool and diminish union influence over the labor market. And second, immigrants may be harder to organize than native

  9. Immigration Stress: Families in Crisis. Resource Guide.

    Science.gov (United States)

    Leon County Schools, Tallahassee, FL.

    This resource guide has been compiled to assist teachers of English for Speakers of Other Languages (ESOL) in meeting the needs of immigrant families. Its purpose is to help reduce immigrant stress by making important information readily available to immigrant families. The guide is divided into the major categories of socialization, education,…

  10. Do Immigrants Underutilize Optometry Services?

    Science.gov (United States)

    Wilson, Fernando A; Wang, Yang; Stimpson, Jim P

    2015-11-01

    To characterize utilization of office-based optometry services by immigration status using a nationally representative database. The 2007 to 2011 Medical Expenditure Panel Survey is used to examine adults aged 18 years and older. Respondents were classified as US natives, naturalized citizens, and noncitizens. Multivariate logistic regression analysis examined the relationship of having visited an office-based optometrist within the past 12 months by immigrant status, adjusting for age, sex, education, race/ethnicity, marital status, self-reported vision difficulty, use of corrective lenses, poverty status, insurance, language barrier and usual source of care. Oaxaca-Blinder decomposition identified factors that perpetuate or ameliorate disparities in utilization across immigrant groups. The proportion of US natives who had visited an optometrist within the past year was 7.2%, almost three times higher than that for noncitizens (2.5%). Among respondents who reported vision difficulties, only 47.9% of noncitizens used corrective lenses compared with 71.0% of naturalized citizens and 71.6% of US natives. Adjusting for confounding factors, multivariate logistic regression showed that naturalized citizens and noncitizen residents had significantly lower odds than US natives of receiving optometry services (naturalized citizen adjusted odds ratio, 0.77; 95% confidence interval, 0.66 to 0.89; noncitizen adjusted odds ratio, 0.44; 95% confidence interval, 0.36 to 0.53). Decomposition analysis suggested that 17% of the disparity in utilization between noncitizens and US natives resulted from barriers to care such as language barriers, poverty, lack of insurance, and not having a usual source of health care. Prior literature suggests that immigrants have significantly poorer clinical vision outcomes than US natives. Our findings suggest that this disparity in clinical vision outcomes may result from underutilization of optometry services by immigrants compared with US

  11. Genetic variation in the major mitotic checkpoint genes associated with chromosomal aberrations in healthy humans

    Czech Academy of Sciences Publication Activity Database

    Försti, A.; Frank, Ch.; Smolková, B.; Kazimírová, A.; Barančoková, M.; Vymetálková, Veronika; Kroupa, M.; Naccarati, Alessio; Vodičková, Ludmila; Buchancová, J.; Dusinská, M.; Musak, L.; Vodička, Pavel; Hemminki, K.

    2016-01-01

    Roč. 380, č. 2 (2016), s. 442-446 ISSN 0304-3835 R&D Projects: GA ČR(CZ) GA15-14789S Institutional support: RVO:68378041 Keywords : chromosomal integrity * cytogenetics * spindle checkpoint Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 6.375, year: 2016

  12. Synthesis of Fault-Tolerant Embedded Systems with Checkpointing and Replication

    DEFF Research Database (Denmark)

    Izosimov, Viacheslav; Pop, Paul; Eles, Petru

    2006-01-01

    We present an approach to the synthesis of fault-tolerant hard real-time systems for safety-critical applications. We use checkpointing with rollback recovery and active replication for tolerating transient faults. Processes are statically scheduled and communications are performed using the time...

  13. Constitutive Cdk2 activity promotes aneuploidy while altering the spindle assembly and tetraploidy checkpoints

    DEFF Research Database (Denmark)

    Jahn, Stephan C; Corsino, Patrick E; Davis, Bradley J

    2013-01-01

    instability. Expression of these complexes in the MCF10A cell line leads to retinoblastoma protein (Rb) hyperphosphorylation, a subsequent increase in proliferation rate, and increased expression of the spindle assembly checkpoint protein Mad2. This results in a strengthening of the spindle assembly...

  14. A phospho-proteomic screen identifies substrates of the checkpoint kinase Chk1

    DEFF Research Database (Denmark)

    Blasius, Melanie; Forment, Josep V; Thakkar, Neha

    2011-01-01

    BACKGROUND: The cell-cycle checkpoint kinase Chk1 is essential in mammalian cells due to its roles in controlling processes such as DNA replication, mitosis and DNA-damage responses. Despite its paramount importance, how Chk1 controls these functions remains unclear, mainly because very few Chk1...

  15. Localization of spindle checkpoint proteins in cells undergoing mitosis with unreplicated genomes.

    Science.gov (United States)

    Johnson, Mary Kathrine; Cooksey, Amanda M; Wise, Dwayne A

    2008-11-01

    CHO cells can be arrested with hydoxyurea at the beginning of the DNA synthesis phase of the cell cycle. Subsequent treatment with the xanthine, caffeine, induces cells to bypass the S-phase checkpoint and enter unscheduled mitosis [Schlegel and Pardee,1986, Science 232:1264-1266]. These treated cells build a normal spindle and distribute kinetochores, unattached to chromosomes, to their daughter cells [Brinkley et al.,1988, Nature 336:251-254; Zinkowski et al.,1991, J Cell Biol 113:1091-1110; Wise and Brinkley,1997, Cell Motil Cytoskeleton 36:291-302; Balczon et al.,2003, Chromosoma 112:96-102]. To investigate how these cells distribute kinetochores to daughter cells, we analyzed the spindle checkpoint components, Mad2, CENP-E, and the 3F3 phosphoepitope, using immunofluorescence and digital microscopy. Even though the kinetochores were unpaired and DNA was fragmented, the tension, alignment, and motor components of the checkpoint were found to be present and localized as predicted in prometaphase and metaphase. This unusual mitosis proves that a cell can successfully localize checkpoint proteins and divide even when kinetochores are unpaired and fragmented. (c) 2008 Wiley-Liss, Inc.

  16. The point of no return: The poly(A)-associated elongation checkpoint.

    Science.gov (United States)

    Tellier, Michael; Ferrer-Vicens, Ivan; Murphy, Shona

    2016-01-01

    Cyclin-dependent kinases play critical roles in transcription by RNA polymerase II (pol II) and processing of the transcripts. For example, CDK9 regulates transcription of protein-coding genes, splicing, and 3' end formation of the transcripts. Accordingly, CDK9 inhibitors have a drastic effect on the production of mRNA in human cells. Recent analyses indicate that CDK9 regulates transcription at the early-elongation checkpoint of the vast majority of pol II-transcribed genes. Our recent discovery of an additional CDK9-regulated elongation checkpoint close to poly(A) sites adds a new layer to the control of transcription by this critical cellular kinase. This novel poly(A)-associated checkpoint has the potential to powerfully regulate gene expression just before a functional polyadenylated mRNA is produced: the point of no return. However, many questions remain to be answered before the role of this checkpoint becomes clear. Here we speculate on the possible biological significance of this novel mechanism of gene regulation and the players that may be involved.

  17. The point of no return: The poly(A)-associated elongation checkpoint

    Science.gov (United States)

    Tellier, Michael; Ferrer-Vicens, Ivan; Murphy, Shona

    2016-01-01

    abstract Cyclin-dependent kinases play critical roles in transcription by RNA polymerase II (pol II) and processing of the transcripts. For example, CDK9 regulates transcription of protein-coding genes, splicing, and 3′ end formation of the transcripts. Accordingly, CDK9 inhibitors have a drastic effect on the production of mRNA in human cells. Recent analyses indicate that CDK9 regulates transcription at the early-elongation checkpoint of the vast majority of pol II-transcribed genes. Our recent discovery of an additional CDK9-regulated elongation checkpoint close to poly(A) sites adds a new layer to the control of transcription by this critical cellular kinase. This novel poly(A)-associated checkpoint has the potential to powerfully regulate gene expression just before a functional polyadenylated mRNA is produced: the point of no return. However, many questions remain to be answered before the role of this checkpoint becomes clear. Here we speculate on the possible biological significance of this novel mechanism of gene regulation and the players that may be involved. PMID:26853452

  18. Immune Checkpoint Inhibitors in the Treatment of Patients with Neuroendocrine Neoplasia.

    Science.gov (United States)

    Weber, Matthias M; Fottner, Christian

    2018-01-01

    Well-differentiated neuroendocrine neoplasms (NENs) are usually controlled by antiproliferative, local ablative and/or radionuclide therapies, whereas poorly differentiated NENs generally require cytotoxic chemotherapy. However, treatment options for patients with advanced/metastatic high-grade NENs remain limited. Review of the literature and international congress abstracts on the efficacy and safety of immunotherapy by checkpoint inhibition in advanced/metastatic NENs. Evidence points to an important role of immune phenomena in the pathogenesis and treatment of neuroendocrine tumors (NETs). Programmed cell death 1 (PD-1) protein and its ligand are mainly expressed in poorly differentiated NENs. Microsatellite instability and high mutational load are more pronounced in high-grade NENs and may predict response to immunotherapy. Clinical experience of immune checkpoint blockade mainly exists for Merkel cell carcinoma, a high-grade cutaneous neuroendocrine carcinoma (NEC), which has led to approval of the anti-PD-1 antibody avelumab. In addition, there is anecdotal evidence for the efficacy of checkpoint inhibitors in large-cell lung NECs, ovarian NECs and others, including gastroenteropancreatic NENs. Currently, phase II studies investigate PDR001, pembrolizumab, combined durvalumab and tremelimumab, and avelumab treatment in patients with advanced/metastatic NENs. Immune checkpoint inhibitors are a promising therapeutic option, especially in progressive NECs or high-grade NETs with high tumor burden, microsatellite instability, and/or mutational load. © 2018 S. Karger GmbH, Freiburg.

  19. Cells bearing chromosome aberrations lacking one telomere are selectively blocked at the G2/M checkpoint

    Energy Technology Data Exchange (ETDEWEB)

    Rodriguez, Pilar [Unitat de Biologia Cel.lular, Departament de Biologia Cel.lular, Fisiologia i Immunologia, Universitat Autonoma de Barcelona, 08193 Bellaterra (Spain); Barquinero, Joan Francesc [Unitat d' Antropologia Biologica, Departament de Biologia Animal, Biologia Vegetal i Ecologia, Universitat Autonoma de Barcelona, 08193 Bellaterra (Spain); Duran, Assumpta [Unitat de Biologia Cel.lular, Departament de Biologia Cel.lular, Fisiologia i Immunologia, Universitat Autonoma de Barcelona, 08193 Bellaterra (Spain); Caballin, Maria Rosa [Unitat d' Antropologia Biologica, Departament de Biologia Animal, Biologia Vegetal i Ecologia, Universitat Autonoma de Barcelona, 08193 Bellaterra (Spain); Ribas, Montserrat [Servei de Radiofisica i Radioproteccio de l' Hospital de la Santa Creu i Sant Pau, 08025 Barcelona (Spain); Barrios, Leonardo, E-mail: Lleonard.Barrios@uab.cat [Unitat de Biologia Cel.lular, Departament de Biologia Cel.lular, Fisiologia i Immunologia, Universitat Autonoma de Barcelona, 08193 Bellaterra (Spain)

    2009-11-02

    Cell cycle checkpoints are part of the cellular mechanisms to maintain genomic integrity. After ionizing radiation exposure, the cells can show delay or arrest in their progression through the cell cycle, as well as an activation of the DNA repair machinery in order to reduce the damage. The G2/M checkpoint prevents G2 cells entering mitosis until the DNA damage has been reduced. The present study evaluates which G0 radiation-induced chromosome aberrations are negatively selected in the G2/M checkpoint. For this purpose, peripheral blood samples were irradiated at 1 and 3 Gy of {gamma}-rays, and lymphocytes were cultured for 48 h. Calyculin-A and Colcemid were used to analyze, in the same slide, cells in G2 and M. Chromosome spreads were consecutively analyzed by solid stain, pancentromeric and pantelomeric FISH and mFISH. The results show that the frequency of incomplete chromosome elements, those lacking a telomeric signal at one end, decreases abruptly from G2 to M. This indicates that cells with incomplete chromosome elements can progress from G0 to G2, but at the G2/M checkpoint suffer a strong negative selection.

  20. Cells bearing chromosome aberrations lacking one telomere are selectively blocked at the G2/M checkpoint

    International Nuclear Information System (INIS)

    Rodriguez, Pilar; Barquinero, Joan Francesc; Duran, Assumpta; Caballin, Maria Rosa; Ribas, Montserrat; Barrios, Leonardo

    2009-01-01

    Cell cycle checkpoints are part of the cellular mechanisms to maintain genomic integrity. After ionizing radiation exposure, the cells can show delay or arrest in their progression through the cell cycle, as well as an activation of the DNA repair machinery in order to reduce the damage. The G2/M checkpoint prevents G2 cells entering mitosis until the DNA damage has been reduced. The present study evaluates which G0 radiation-induced chromosome aberrations are negatively selected in the G2/M checkpoint. For this purpose, peripheral blood samples were irradiated at 1 and 3 Gy of γ-rays, and lymphocytes were cultured for 48 h. Calyculin-A and Colcemid were used to analyze, in the same slide, cells in G2 and M. Chromosome spreads were consecutively analyzed by solid stain, pancentromeric and pantelomeric FISH and mFISH. The results show that the frequency of incomplete chromosome elements, those lacking a telomeric signal at one end, decreases abruptly from G2 to M. This indicates that cells with incomplete chromosome elements can progress from G0 to G2, but at the G2/M checkpoint suffer a strong negative selection.

  1. Myasthenia triggered by immune checkpoint inhibitors: New case and literature review.

    Science.gov (United States)

    Gonzalez, Natalia L; Puwanant, Araya; Lu, Angela; Marks, Stanley M; Živković, Saša A

    2017-03-01

    Immune checkpoint molecules are potent regulators of immunologic homeostasis that prevent the development of autoimmunity while maintaining self-tolerance. Inhibitors of immune checkpoint molecules are used as immunotherapy in the treatment of melanoma and different types of refractory cancer, and can trigger various autoimmune complications including myositis and myasthenia gravis. We describe a case of generalized myasthenia gravis induced by pembrolizumab and review 11 other cases. Five patients also had elevated serum CK levels ranging from 1200 to 8729 IU/L, and biopsy showed myositis in one. Severity was highly variable as symptoms normalized spontaneously in one patient, but three others developed myasthenic crisis (including two with fatal outcomes). Steroids have been recommended as a preferred treatment of autoimmune complications of immune-checkpoint inhibitors. Myasthenia gravis should be considered when weakness, diplopia or bulbar symptoms are seen after treatment with immune checkpoint inhibitors, and additional studies are needed to characterize association with hyperCKemia. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. rad-Dependent response of the chk1-encoded protein kinase at the DNA damage checkpoint

    NARCIS (Netherlands)

    Walworth, N.C.; Bernards, R.A.

    1996-01-01

    Exposure of eukaryotic cells to agents that generate DNA damage results in transient arrest of progression through the cell cycle. In fission yeast, the DNA damage checkpoint associated with cell cycle arrest before mitosis requires the protein kinase p56chk1. DNA damage induced by ultraviolet

  3. Differential impact of diverse anticancer chemotherapeutics on the Cdc25A-degradation checkpoint pathway

    International Nuclear Information System (INIS)

    Agner, Jeppe; Falck, Jacob; Lukas, Jiri; Bartek, Jiri

    2005-01-01

    When exposed to DNA-damaging insults such as ionizing radiation (IR) or ultraviolet light (UV), mammalian cells activate checkpoint pathways to halt cell cycle progression or induce cell death. Here we examined the ability of five commonly used anticancer drugs with different mechanisms of action to activate the Chk1/Chk2-Cdc25A-CDK2/cyclin E cell cycle checkpoint pathway, previously shown to be induced by IR or UV. Whereas exposure of human cells to topoisomerase inhibitors camptothecin, etoposide, or adriamycin resulted in rapid (within 1 h) activation of the pathway including degradation of the Cdc25A phosphatase and inhibition of cyclin E/CDK2 kinase activity, taxol failed to activate this checkpoint even after a prolonged treatment. Unexpectedly, although the alkylating agent cisplatin also induced degradation of Cdc25A (albeit delayed, after 8-12 h), cyclin E/CDK2 activity was elevated and DNA synthesis continued, a phenomena that correlated with increased E2F1 protein levels and consequently enhanced expression of cyclin E. These results reveal a differential impact of various classes of anticancer chemotherapeutics on the Cdc25A-degradation pathway, and indicate that the kinetics of checkpoint induction, and the relative balance of key components within the DNA damage response network may dictate whether the treated cells arrest their cell cycle progression

  4. Immunogenic Chemotherapy Sensitizes Renal Cancer to Immune Checkpoint Blockade Therapy in Preclinical Models.

    Science.gov (United States)

    Cui, Shujin

    2017-07-11

    BACKGROUND Renal cell carcinoma (RCC) is among the most common malignant cancers of males worldwide. For advanced RCC patients, there still is no effective therapy. Immune checkpoint blockade therapies have shown benefits for many cancers, but previous clinical trials of immune checkpoint blockade therapies in RCC patients achieved only modest results. MATERIAL AND METHODS We explored the effects of combining chemotherapy with immune checkpoint blockade therapy in RCC xenograft mouse models. We also studied the potential mechanisms by which chemotherapy might enhance the efficacy of immune checkpoint blockade therapy, both in vitro and in vivo. RESULTS Our results showed that many commonly used chemotherapy agents can induce immunogenic marker release in RCC cell lines. Importantly, the RCC xenograft mouse model mice who received the combination treatment of 5-fluorouracil (5-FU) and anti-programmed cell death-ligand 1 (PD-L1) antibodies (Abs) had longer survival times compared to those who received 5-FU or anti-PD-L1 Abs alone. Also, increased key cytokines that promote tumor immunity, such as IL-2, IFN-γ, and TNF-α, as well as tumor-infiltrating cytotoxic T cells, were also increased after the combination treatment. CONCLUSIONS We conclude that 5-FU can sensitize RCC to anti-PD-L1 treatment by releasing the immune suppression in the tumor microenvironment.

  5. Prevalence of non-food allergies among non-immigrants, long-time immigrants and recent immigrants in Canada.

    Science.gov (United States)

    Yao, Jiayun; Sbihi, Hind

    2016-12-27

    The prevalence of allergic conditions has been increasing worldwide, with the highest rates seen in Western countries like Canada. The development of allergies is known to be related to both genetic and environmental factors, but the causal pathways remain unclear. Studies on immigrants provide a unique opportunity to disentangle these two factors and provide a better understanding of the disease aetiology. The aim of this study was to investigate the relationship between immigration status and prevalence of non-food allergies in a population-based study of Canadians. Data of 116,232 respondents from the Canadian Community Health Survey (Cycle 3.1, 2005) were used in a multivariable logistic regression to assess the association between immigration status (non-immigrant, long-time immigrant [>10 years] and recent immigrant [≤10 years]) and self-reported doctor-diagnosed non-food allergies, adjusting for potential confounders. The highest prevalence of non-food allergies was found among non-immigrants (29.6%), followed by long-time immigrants (23.9%) and then recent immigrants (14.3%). The odds of non-food allergies were reduced by 60% (OR = 0.40, 95% CI: 0.35, 0.45) among recent immigrants and 25% (OR = 0.75, 95% CI: 0.70, 0.80) among long-time immigrants, compared with non-immigrants, after adjusting for sex, age, socio-economic status and rurality. This study finds a distinctly lower prevalence of non-food allergies among immigrants compared with non-immigrants, with the difference diminishing with longer duration of residence in Canada. The findings highlight the potential of environmental determinants of allergy development that warrant further investigation, and demonstrate the need for multicultural strategies to manage the public health burden of allergic conditions.

  6. Correlates of Social Support Among Latino Immigrants.

    Science.gov (United States)

    Held, Mary L

    2018-04-01

    Latino immigrants encounter considerable stressors that pose risks to health and well-being during settlement in the USA. Social support serves as a protective factor that can help to buffer the negative effects of stress. Despite the importance of social support, we know little about how Latino immigrants differentially experience this protective factor. The current study analyzed data from 100 Latino immigrants residing in Tennessee. Hierarchical multiple regression analysis was employed to examine variation in self-reported social support by immigrant characteristics and immigration-related factors. Females, immigrants who are not married/cohabitating, and those who reported experiencing a greater number of discrete stressors in the USA each reported lower levels of social support. Implications for practice include an increased emphasis on assessing levels of social support and designing services to strengthen support for the most vulnerable immigrants. Future research should consider a longitudinal analysis and specific types of social support.

  7. The emerging role of immune checkpoint based approaches in AML and MDS.

    Science.gov (United States)

    Boddu, Prajwal; Kantarjian, Hagop; Garcia-Manero, Guillermo; Allison, James; Sharma, Padmanee; Daver, Naval

    2018-04-01

    The development of immune checkpoint inhibitors represents a major breakthrough in the field of cancer therapeutics. Pursuant to their success in melanoma and numerous solid tumor malignancies, these agents are being investigated in hematological malignancies including acute myelogenous leukemia (AML) and myelodysplastic syndromes (MDS). Although AML/MDS have traditionally been considered to be less immunogenic than solid tumor malignancies, recent pre-clinical models suggest a therapeutic role for immune checkpoint inhibition in these diseases. CTLA-4 inhibition may be especially effective in treating late post-allogeneic stem cell transplant relapse of AML in patients with limited or no graft versus host disease. Immune checkpoint inhibition, specifically PD-1 inhibition, demonstrated limited single agent efficacy in patients with relapsed AML and with MDS post-hypomethylating therapy. Rationally designed combinations of PD-1 inhibitors with standard anti-leukemic therapy are needed. Hypomethylating agents such as azacitidine, up-regulate PD-1, PD-L1, and PD-L2 in patients with AML/MDS and up-regulation of these genes was associated with the emergence of resistance. The combination of azacitidine and PD-1/PD-L1 inhibition may be a potential mechanism to prevent or overcome resistance to 5-azacitidine. A number of such combinations are being evaluated in clinical trials with early encouraging results. Immune checkpoint inhibition is also an attractive option to improve relapse-free survival or eliminate minimal residual disease post induction and consolidation by enhancing T-cell surveillance in patients with high-risk AML. The ongoing clinical trials with checkpoint inhibitors in AML/MDS will improve our understanding of the immunobiology of these diseases and guide us to the most appropriate application of these agents in the therapy of AML/MDS.

  8. [Sea urchin embryo, DNA-damaged cell cycle checkpoint and the mechanisms initiating cancer development].

    Science.gov (United States)

    Bellé, Robert; Le Bouffant, Ronan; Morales, Julia; Cosson, Bertrand; Cormier, Patrick; Mulner-Lorillon, Odile

    2007-01-01

    Cell division is an essential process for heredity, maintenance and evolution of the whole living kingdom. Sea urchin early development represents an excellent experimental model for the analysis of cell cycle checkpoint mechanisms since embryonic cells contain a functional DNA-damage checkpoint and since the whole sea urchin genome is sequenced. The DNA-damaged checkpoint is responsible for an arrest in the cell cycle when DNA is damaged or incorrectly replicated, for activation of the DNA repair mechanism, and for commitment to cell death by apoptosis in the case of failure to repair. New insights in cancer biology lead to two fundamental concepts about the very first origin of cancerogenesis. Cancers result from dysfunction of DNA-damaged checkpoints and cancers appear as a result of normal stem cell (NCS) transformation into a cancer stem cell (CSC). The second aspect suggests a new definition of "cancer", since CSC can be detected well before any clinical evidence. Since early development starts from the zygote, which is a primary stem cell, sea urchin early development allows analysis of the early steps of the cancerization process. Although sea urchins do not develop cancers, the model is alternative and complementary to stem cells which are not easy to isolate, do not divide in a short time and do not divide synchronously. In the field of toxicology and incidence on human health, the sea urchin experimental model allows assessment of cancer risk from single or combined molecules long before any epidemiologic evidence is available. Sea urchin embryos were used to test the worldwide used pesticide Roundup that contains glyphosate as the active herbicide agent; it was shown to activate the DNA-damage checkpoint of the first cell cycle of development. The model therefore allows considerable increase in risk evaluation of new products in the field of cancer and offers a tool for the discovery of molecular markers for early diagnostic in cancer biology

  9. Caenorhabditis elegans histone methyltransferase MET-2 shields the male X chromosome from checkpoint machinery and mediates meiotic sex chromosome inactivation.

    Directory of Open Access Journals (Sweden)

    Paula M Checchi

    2011-09-01

    Full Text Available Meiosis is a specialized form of cellular division that results in the precise halving of the genome to produce gametes for sexual reproduction. Checkpoints function during meiosis to detect errors and subsequently to activate a signaling cascade that prevents the formation of aneuploid gametes. Indeed, asynapsis of a homologous chromosome pair elicits a checkpoint response that can in turn trigger germline apoptosis. In a heterogametic germ line, however, sex chromosomes proceed through meiosis with unsynapsed regions and are not recognized by checkpoint machinery. We conducted a directed RNAi screen in Caenorhabditis elegans to identify regulatory factors that prevent recognition of heteromorphic sex chromosomes as unpaired and uncovered a role for the SET domain histone H3 lysine 9 histone methyltransferase (HMTase MET-2 and two additional HMTases in shielding the male X from checkpoint machinery. We found that MET-2 also mediates the transcriptional silencing program of meiotic sex chromosome inactivation (MSCI but not meiotic silencing of unsynapsed chromatin (MSUC, suggesting that these processes are distinct. Further, MSCI and checkpoint shielding can be uncoupled, as double-strand breaks targeted to an unpaired, transcriptionally silenced extra-chromosomal array induce checkpoint activation in germ lines depleted for met-2. In summary, our data uncover a mechanism by which repressive chromatin architecture enables checkpoint proteins to distinguish between the partnerless male X chromosome and asynapsed chromosomes thereby shielding the lone X from inappropriate activation of an apoptotic program.

  10. The Pch2 AAA+ ATPase promotes phosphorylation of the Hop1 meiotic checkpoint adaptor in response to synaptonemal complex defects.

    Science.gov (United States)

    Herruzo, Esther; Ontoso, David; González-Arranz, Sara; Cavero, Santiago; Lechuga, Ana; San-Segundo, Pedro A

    2016-09-19

    Meiotic cells possess surveillance mechanisms that monitor critical events such as recombination and chromosome synapsis. Meiotic defects resulting from the absence of the synaptonemal complex component Zip1 activate a meiosis-specific checkpoint network resulting in delayed or arrested meiotic progression. Pch2 is an evolutionarily conserved AAA+ ATPase required for the checkpoint-induced meiotic block in the zip1 mutant, where Pch2 is only detectable at the ribosomal DNA array (nucleolus). We describe here that high levels of the Hop1 protein, a checkpoint adaptor that localizes to chromosome axes, suppress the checkpoint defect of a zip1 pch2 mutant restoring Mek1 activity and meiotic cell cycle delay. We demonstrate that the critical role of Pch2 in this synapsis checkpoint is to sustain Mec1-dependent phosphorylation of Hop1 at threonine 318. We also show that the ATPase activity of Pch2 is essential for its checkpoint function and that ATP binding to Pch2 is required for its localization. Previous work has shown that Pch2 negatively regulates Hop1 chromosome abundance during unchallenged meiosis. Based on our results, we propose that, under checkpoint-inducing conditions, Pch2 also possesses a positive action on Hop1 promoting its phosphorylation and its proper distribution on unsynapsed chromosome axes. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  11. Digital Immigrants in Distance Education

    Science.gov (United States)

    Salazar-Márquez, Roberto

    2017-01-01

    The constant growth of methods of education that incorporate the Internet into teaching-learning processes has opened up a wide range of opportunities for students across the world to gain entry to undergraduate or graduate degree programs. However, if the enrolling student is a digital immigrant, the chances of success may be limited by the…

  12. Immigrants in Slovenia: Integration Aspects

    Directory of Open Access Journals (Sweden)

    Janja Žitnik

    2004-09-01

    Full Text Available On the basis of the latest statistics, the author estimates the present share of first- and second-generation immigrants in Slovenia’s population. After examining the quantity and intensity of those public efforts in Slovenia that have been focused on unresolved problems of the immigrants’ social and cultural integration, she continues to question the equality of immigrant minorities in Slovenia, and the sufficiency of the existing programs aimed at facilitating their integration with Slovenian society at large. She explains her doubts about the general assumption that a very clear distinction should be made between the rights of the autochthonous minorities and those of the immigrant ones as far as their special protection is concerned. In the third section of this article, the author discusses the social-ethnic stratification of Slovenian society and tries to look into the psychological background of the nationality/ethnicity statistics. She presents some aspects of the immigrants’ daily experience in Slovenian social, cultural, educational and working milieu, and points to the authorities’ attitude toward them. She comments on the burning issue of the “deleted residents”, and illustrates it with the experience of one of the persons involved. The fourth section, in which the most regular symptoms of Slovenian xenophobia are presented, consists of first-hand observations and focuses on the daily human attitude of the national majority towards the immigrant minorities. Finally the author compares the nature of the specific needs of Slovenians as a “European national minority” with the needs of the immigrant minorities in Slovenia.

  13. Costs of berm and causeway alternatives

    International Nuclear Information System (INIS)

    Kubo, Arthur S.

    1987-01-01

    Experiments initiated in February 1985 and still in progress have demonstrated that removal of 30 cm of topsoil brings the specific activity of Bikini Island soil down to the level of that on Eneu and reduces the external exposure rate to gamma rays from an average of 68 pr/h to 5 pr/h. The analytical data completed thus far for food crops grown in the experimental and control areas indicate a parallel response. During 1986 results became available showing that removal of topsoil would also limit productivity. However, it is now known that with adequate care the excavated plot can be as productive as the unexcavated (natural) one. The removal of 30 cm (1 foot) of topsoil at Bikini Island would produce large amounts of waste vegetable matter and approximately 719,000 cubic meters of contaminated topsoil. Three principal alternatives have been considered for the disposal of the spoil. The cost estimates for these and other rehabilitation alternatives were developed in detail by a panel of engineers, chaired by BARC member Arthur S. Kubo, which met in January 1986. The panel's report constitutes Appendix C of BARC Report No. 4

  14. Costs of berm and causeway alternatives

    Energy Technology Data Exchange (ETDEWEB)

    Kubo, Arthur S [Bikini Atoll Rehabilitation Committee, Berkeley, CA (United States); [BDM Corporation, McLean, VA (United States)

    1987-07-01

    Experiments initiated in February 1985 and still in progress have demonstrated that removal of 30 cm of topsoil brings the specific activity of Bikini Island soil down to the level of that on Eneu and reduces the external exposure rate to gamma rays from an average of 68 pr/h to 5 pr/h. The analytical data completed thus far for food crops grown in the experimental and control areas indicate a parallel response. During 1986 results became available showing that removal of topsoil would also limit productivity. However, it is now known that with adequate care the excavated plot can be as productive as the unexcavated (natural) one. The removal of 30 cm (1 foot) of topsoil at Bikini Island would produce large amounts of waste vegetable matter and approximately 719,000 cubic meters of contaminated topsoil. Three principal alternatives have been considered for the disposal of the spoil. The cost estimates for these and other rehabilitation alternatives were developed in detail by a panel of engineers, chaired by BARC member Arthur S. Kubo, which met in January 1986. The panel's report constitutes Appendix C of BARC Report No. 4.

  15. Participation of SRM5/CDC28, SRM8/NET1 and SRM12/HF11 genes in activation of checkpoints of Yeast Saccharomyces Cerevisiae

    International Nuclear Information System (INIS)

    Kadyshevskaya, E.Yu.; Koltovaya, N.A.

    2007-01-01

    It is known that there are about twenty checkpoint genes in yeast Saccharomyces cerevisiae. We study participation of SRM genes selected as genes affecting genetic stability and radiosensitivity. It has been shown that srm5/cdc28-srm, srm8/net1-srm, srm12/hfil-srm mutations prevent checkpoint activation by DNA damage, particularly G0/S-checkpoint (srm5, srm8), G1/S-checkpoint (srm5, srm8, srm12), S-checkpoint (srm5, srm12) and G2-checkpoint (srm5). These data indicate, at least in budding yeast, CDC28/SRM5, HF11/ADA1/SRM12 and NET1/SRM8 genes mediate cellular response induced by DNA damage including checkpoint control

  16. Contextualizing immigrants' lived experience: story of Taiwanese immigrants in the United States.

    Science.gov (United States)

    Tsai, Jenny Hsin-Chun

    2003-01-01

    Immigration involves extensive changes in living environments. Nonetheless, the predominant approach in the health science literature has been to utilize individual characteristics (including ethnic background) to explain and predict immigrants' lived experiences and health outcomes. Contexts, particularly the larger societal contexts by which immigrants are constituted, are generally ignored. Data from a critical ethnography regarding immigrants' experiences with language, occupation, and economic survival in the United States are utilized to illustrate that immigrants' lives are inseparable from the larger societal contexts, such as immigration policy, Western imperialism, and structural discrimination. The implications for practice, education, and research are discussed.

  17. 28 CFR 0.117 - Office of Chief Immigration Judge.

    Science.gov (United States)

    2010-07-01

    ... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Office of Chief Immigration Judge. 0.117... Executive Office for Immigration Review § 0.117 Office of Chief Immigration Judge. The Chief Immigration Judge shall provide general supervision to the Immigration Judges in performance of their duties in...

  18. Is Temporary Agency Employment a Stepping Stone for Immigrants?

    OpenAIRE

    Jahn, Elke J.; Rosholm, Michael

    2012-01-01

    We investigate whether agency employment is a bridge into regular employment for immigrants to Denmark using the timing-of-events approach. We provide evidence of large positive in-treatment effects, particularly for non-western immigrants and immigrants arriving during childhood. Post-treatment effects are fairly high for male non-western immigrants and immigrants from Eastern Europe.

  19. Challenging Preservice Teacher Perspectives: Immigration, Equitable Opportunity, and Advocacy

    Science.gov (United States)

    Nino, Mary Catherine

    2012-01-01

    In this conceptual article, I use five questions that were posed in 1936 about immigration and the education of immigrant children as a lens to examine contemporary perspectives on immigration and the education of immigrant children. Dispelling myths about immigrant students and English learners has been a consistent concern in our country. These…

  20. [Tuberculosis and immigration in Spain: scoping review].

    Science.gov (United States)

    Casals, Martí; Rodrigo, Teresa; Camprubí, Esteve; Orcau, Angels; Caylà, Joan A

    2014-01-01

    Immigration is a fairly recent phenomenon in Spain and there are still few scientific publications on tuberculosis (TB) and immigration. Therefore, the aim of this study is to describe the differential characteristics of TB in the immigrant population with respect to natives in Spain. Literature review of original articles written in Spanish or English and published 1998-2012 about TB among immigrant population. The articles with the key words "Tuberculosis", "immigrants" and "Spain" were included. Literature search was performed in Medline and MEDES. A total of 72,087 articles on TB were detected worldwide, 6% of them dealt with the immigration issue. Regarding Spain we found 2,917 articles representing 4% of the papers published worldwide, and in 219 (7.5%) immigration was considered. Of the 219 articles, 48% were published in Spanish journals and the 52% remaining in Anglo-Saxon journals. 93.5% of immigrants with TB were younger than 51, whereas this percentage was 64.9% in natives. Drug resistance can be seen in 7.8% of the immigrant population but in only 3.8% of natives. It was also detected that the unavailability of a health card could be a problem. Immigrants with TB were characterized by being younger and having more drug resistance and coming mostly from Latin America, Eastern Europe, Africa and Asia. It was also detected that the unavailability of a health card could be a problem.

  1. To what extent does immigration affect inequality?

    Science.gov (United States)

    Berman, Yonatan; Aste, Tomaso

    2016-11-01

    The current surge in income and wealth inequality in most western countries, along with the continuous immigration to those countries demand a quantitative analysis of the effect immigration has on economic inequality. This paper presents a quantitative analysis framework providing a way to calculate this effect. It shows that in most cases, the effect of immigration on wealth and income inequality is limited, mainly due to the relative small scale of immigration waves. For a large scale flow of immigrants, such as the immigration to the US, the UK and Australia in the past few decades, we estimate that 10 % ÷ 15 % of the wealth and income inequality increase can be attributed to immigration. The results demonstrate that immigration could possibly decrease inequality substantially, if the characteristics of the immigrants resemble the characteristics of the destination middle class population in terms of wealth or income. We empirically found that the simple linear relation ΔS = 0.18 ρ roughly describes the increase in the wealth share of the top 10 % due to immigration of a fraction ρ of the population.

  2. Casein kinase II is required for the spindle assembly checkpoint by regulating Mad2p in fission yeast

    Energy Technology Data Exchange (ETDEWEB)

    Shimada, Midori [Department of Biochemistry and Cell Biology, Graduate School of Medicine, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601 (Japan); Yamamoto, Ayumu [Department of Chemistry, Shizuoka University, 836 Ohya, Suruga-ku, Sizuoka 422-8529 (Japan); Murakami-Tonami, Yuko; Nakanishi, Makoto; Yoshida, Takashi [Department of Biochemistry and Cell Biology, Graduate School of Medicine, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601 (Japan); Aiba, Hirofumi [Laboratory of Molecular Microbiology, School of Agriculture, Nagoya University, Chikusa-ku, Nagoya 464-8601 (Japan); Murakami, Hiroshi, E-mail: hmura@med.nagoya-cu.ac.jp [Department of Biochemistry and Cell Biology, Graduate School of Medicine, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601 (Japan)

    2009-10-23

    The spindle checkpoint is a surveillance mechanism that ensures the fidelity of chromosome segregation in mitosis. Here we show that fission yeast casein kinase II (CK2) is required for this checkpoint function. In the CK2 mutants mitosis occurs in the presence of a spindle defect, and the spindle checkpoint protein Mad2p fails to localize to unattached kinetochores. The CK2 mutants are sensitive to the microtubule depolymerising drug thiabendazole, which is counteracted by ectopic expression of mad2{sup +}. The level of Mad2p is low in the CK2 mutants. These results suggest that CK2 has a role in the spindle checkpoint by regulating Mad2p.

  3. What is the Right to Exclude Immigrants?

    DEFF Research Database (Denmark)

    Lægaard, Sune

    2010-01-01

    It is normally taken for granted that states have a right to control immigration into their territory. When immigration is raised as a normative issue two questions become salient, one about what the right to exclude is, and one about whether and how it might be justified. This paper considers...... the first question. The paper starts by noting that standard debates about immigration have not addressed what the right to exclude is. Standard debates about immigration furthermore tend to result either in fairly strong cases for open borders or in denials that considerations of justice apply...... to immigration at all, which results in state discretion positions. This state of debate is both theoretically unsatisfactory and normatively implausible. The paper therefore explores an alternative approach to the right to exclude immigrants from the perspective of recent debates about the territorial rights...

  4. [Psychotherapy with Immigrants and Traumatized Refugees].

    Science.gov (United States)

    Erim, Yesim; Morawa, Eva

    2016-09-01

    In view of the growing proportion of immigrants and refugees in the population of Germany the knowledge on the influence of culture and migration on identity, and mental health presents a substantial basis for effective therapy. This article addresses important topics of psychotherapy with immigrants in general and with refugees in particular. Following issues selected according to their relevance and actuality are highlighted: definition of persons with migration background, migrants and refugees, facts on immigration to Germany, main results and theories on mental health of immigrants, social psychological aspects of intercultural psychotherapy (individualism vs. collectivism, stereotypes, discrimination etc.), psychosomatic diagnostics in intercultural context, diversity management in institutions, language and use of translators, living conditions of immigrants - stress and protective factors in immigrant mental health, post traumatic stress disorders among refugees: their prevalence, risk factors, diagnostics, course, multimodal psychosocial interventions in consulting centers, trauma focused interventions, trauma pedagogics, education and prevention of the volunteers. © Georg Thieme Verlag KG Stuttgart · New York.

  5. RNA interference regulates the cell cycle checkpoint through the RNA export factor, Ptr1, in fission yeast

    Energy Technology Data Exchange (ETDEWEB)

    Iida, Tetsushi, E-mail: tiida@nig.ac.jp [Division of Cytogenetics, National Institute of Genetics, Mishima, 1111 Yata, Mishima 411-8540 (Japan); The Graduate University for Advanced Studies, Sokendai, Mishima, 1111 Yata, Mishima 411-8540 (Japan); Precursory Research for Embryonic Science and Technology (PRESTO), Japan Science and Technology Agency (JST), 4-1-8, Honcho, Kawaguchi-shi, Saitama 332-0012 (Japan); Iida, Naoko [Division of Mutagenesis, National Institute of Genetics, Mishima, 1111 Yata, Mishima 411-8540 (Japan); Tsutsui, Yasuhiro [Department of Life Science, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Nagatsuda-cho, Midori-ku, Yokohama 226-8501 (Japan); Yamao, Fumiaki [Division of Mutagenesis, National Institute of Genetics, Mishima, 1111 Yata, Mishima 411-8540 (Japan); The Graduate University for Advanced Studies, Sokendai, Mishima, 1111 Yata, Mishima 411-8540 (Japan); Kobayashi, Takehiko [Division of Cytogenetics, National Institute of Genetics, Mishima, 1111 Yata, Mishima 411-8540 (Japan); The Graduate University for Advanced Studies, Sokendai, Mishima, 1111 Yata, Mishima 411-8540 (Japan)

    2012-10-12

    Highlights: Black-Right-Pointing-Pointer RNAi is linked to the cell cycle checkpoint in fission yeast. Black-Right-Pointing-Pointer Ptr1 co-purifies with Ago1. Black-Right-Pointing-Pointer The ptr1-1 mutation impairs the checkpoint but does not affect gene silencing. Black-Right-Pointing-Pointer ago1{sup +} and ptr1{sup +} regulate the cell cycle checkpoint via the same pathway. Black-Right-Pointing-Pointer Mutations in ago1{sup +} and ptr1{sup +} lead to the nuclear accumulation of poly(A){sup +} RNAs. -- Abstract: Ago1, an effector protein of RNA interference (RNAi), regulates heterochromatin silencing and cell cycle arrest in fission yeast. However, the mechanism by which Ago1 controls cell cycle checkpoint following hydroxyurea (HU) treatment has not been elucidated. In this study, we show that Ago1 and other RNAi factors control cell cycle checkpoint following HU treatment via a mechanism independent of silencing. While silencing requires dcr1{sup +}, the overexpression of ago1{sup +} alleviated the cell cycle defect in dcr1{Delta}. Ago1 interacted with the mRNA export factor, Ptr1. The ptr1-1 mutation impaired cell cycle checkpoint but gene silencing was unaffected. Genetic analysis revealed that the regulation of cell cycle checkpoint by ago1{sup +} is dependent on ptr1{sup +}. Nuclear accumulation of poly(A){sup +} RNAs was detected in mutants of ago1{sup +} and ptr1{sup +}, suggesting there is a functional link between the cell cycle checkpoint and RNAi-mediated RNA quality control.

  6. Gender, immigration, and school victimization

    OpenAIRE

    Peguero, Anthony A.a

    2012-01-01

    Anthony Peguero speaks about his research on adolescent violence, socialization and marginalization, school bullying, race and ethnicity, and the adaptation of the children immigrants. It is well established that violence can seriously lead to mental health disorders, disrupt interpersonal social relationships, derail educational progress, and negatively impact life-course trajectories for youth. Despite the prevalence and problems associated with youth violence, studies that examine the disp...

  7. digital natives and digital immigrants

    OpenAIRE

    Cardina, Bruno; Francisco, Jerónimo; Reis, Pedro; trad. Silva, Fátima

    2011-01-01

    This article focuses on the generational gaps in school learning. Initially, we have tried to provide the framework in relation to the term digital native in order to understand the key aspects of the generation born after the advent and the global use of the Internet. They were found to be “multitasking” people, linked to technology and connectivity, as opposed to digital immigrants, born in an earlier period and seeking to adapt to the technological world. We also present some r...

  8. Immune Checkpoint Inhibitors: A New Opportunity in the Treatment of Ovarian Cancer?

    Directory of Open Access Journals (Sweden)

    Gloria Mittica

    2016-07-01

    Full Text Available Epithelial ovarian cancer (EOC is the leading cause of death for gynecological cancer. The standard treatment for advanced stage is the combination of optimal debulking surgery and platinum-based chemotherapy. Nevertheless, recurrence is frequent (around 70% and prognosis is globally poor. New therapeutic agents are needed to improve survival. Since EOC is strongly immunogenic, immune checkpoint inhibitors are under evaluation for their capacity to contrast the “turn off” signals expressed by the tumor to escape the immune system and usually responsible for self-tolerance maintenance. This article reviews the literature on anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4, anti-PD-1, anti-PD-L1, and anti-PD-L2 antibodies in EOC and highlights their possible lines of development. Further studies are needed to better define the prognostic role of the immune checkpoint inhibitors, to identify predictors of response and the optimal clinical setting in EOC.

  9. Immune Checkpoint Inhibitors: An Innovation in Immunotherapy for the Treatment and Management of Patients with Cancer.

    Science.gov (United States)

    Dine, Jennifer; Gordon, RuthAnn; Shames, Yelena; Kasler, Mary Kate; Barton-Burke, Margaret

    2017-01-01

    Cancer survival rates are generally increasing in the United States. These trends have been partially attributed to improvement in therapeutic strategies. Cancer immunotherapy is an example of one of the newer strategies used to fight cancer, which primes or activates the immune system to produce antitumor effects. The first half of this review paper concisely describes the cell mechanisms that control antitumor immunity and the major immunotherapeutic strategies developed to target these mechanisms. The second half of the review discusses in greater depth immune checkpoint inhibitors that have recently demonstrated tremendous promise for the treatment of diverse solid tumor types, including melanoma, non-small cell lung cancer, and others. More specifically, the mechanisms of action, side effects, and patient and family management and education concerns are discussed to provide oncology nurses up-to-date information relevant to caring for cancer-affected patients treated with immune checkpoint inhibitors. Future directions for cancer immunotherapy are considered.

  10. The fission yeast spindle orientation checkpoint: a model that generates tension?

    Science.gov (United States)

    Gachet, Yannick; Reyes, Céline; Goldstone, Sherilyn; Tournier, Sylvie

    2006-10-15

    In all eukaryotes, the alignment of the mitotic spindle with the axis of cell polarity is essential for accurate chromosome segregation as well as for the establishment of cell fate, and thus morphogenesis, during development. Studies in invertebrates, higher eukaryotes and yeast suggest that astral microtubules interact with the cell cortex to position the spindle. These microtubules are thought to impose pushing or pulling forces on the spindle poles to affect the rotation or movement of the spindle. In the fission yeast model, where cell division is symmetrical, spindle rotation is dependent on the interaction of astral microtubules with the cortical actin cytoskeleton. In these cells, a bub1-dependent mitotic checkpoint, the spindle orientation checkpoint (SOC), is activated when the spindles fail to align with the cell polarity axis. In this paper we review the mechanism that orientates the spindle during mitosis in fission yeast, and discuss the consequences of misorientation on metaphase progression. Copyright 2006 John Wiley & Sons, Ltd.

  11. Cloud object store for checkpoints of high performance computing applications using decoupling middleware

    Science.gov (United States)

    Bent, John M.; Faibish, Sorin; Grider, Gary

    2016-04-19

    Cloud object storage is enabled for checkpoints of high performance computing applications using a middleware process. A plurality of files, such as checkpoint files, generated by a plurality of processes in a parallel computing system are stored by obtaining said plurality of files from said parallel computing system; converting said plurality of files to objects using a log structured file system middleware process; and providing said objects for storage in a cloud object storage system. The plurality of processes may run, for example, on a plurality of compute nodes. The log structured file system middleware process may be embodied, for example, as a Parallel Log-Structured File System (PLFS). The log structured file system middleware process optionally executes on a burst buffer node.

  12. A Comprehensive Review of US FDA-Approved Immune Checkpoint Inhibitors in Urothelial Carcinoma

    Directory of Open Access Journals (Sweden)

    Fu-Shun Hsu

    2017-01-01

    Full Text Available Few effective treatment options are available for patients with advanced or metastatic urothelial carcinoma (UC after unsuccessful first-line platinum-based chemotherapy. To date, immune checkpoint inhibitors are novel therapeutic agents for UC treatment. From May 2016 to May 2017, five anti-PD-1/PD-L1 monoclonal antibodies received accelerated or regular approval from the US Food and Drug Administration (FDA for the treatment of patients with locally advanced or metastatic UC. The present comprehensive review presents the background information of these five US FDA-approved anticancer agents to provide a basic but concise understanding of these agents for advanced studies. We summarize their immune checkpoint mechanisms, clinical efficacy, recommended usage protocols, adverse events, and the limitations of the PD-L1 biomarker assays.

  13. Immigrants as Active Citizens: Exploring the Volunteering Experience of Chinese Immigrants in Vancouver

    Science.gov (United States)

    Guo, Shibao

    2014-01-01

    Despite the fact that immigration has played an important role in transforming Canada into an ethno-culturally diverse and economically prosperous nation, immigrants themselves are often criticised as passive citizens. This study attempts to deconstruct this myth by investigating the volunteering experiences of Chinese immigrants in Vancouver. The…

  14. Consequences of Arizona's Immigration Policy on Social Capital among Mexican Mothers with Unauthorized Immigration Status

    Science.gov (United States)

    Valdez, Carmen R.; Padilla, Brian; Valentine, Jessa Lewis

    2013-01-01

    This study explores the consequences of increasingly restrictive immigration policies on social capital among Mexican mothers with unauthorized immigrant status in Arizona. Three focus groups conducted in Arizona explore how mothers' experiences with immigration policies have affected their neighborhood, community, and family ties. Focus group…

  15. Age at immigration and the incomes of older immigrants, 1994-2010.

    Science.gov (United States)

    O'Neil, Kevin; Tienda, Marta

    2015-03-01

    Seniors comprise a growing proportion of new U.S. immigrants. We investigate whether late-age immigrants are disadvantaged in older age relative to those arriving earlier in life, based on income, reliance on public benefits, and access to public medical insurance. We test whether the 1996 welfare reform law altered the relationships between age at immigration and these outcomes. Immigrants aged 65 and older in the 1994-2010 Current Population Surveys were classified by age at immigration. Median and logistic regressions are used to estimate the association between age at immigration and several outcomes and to test whether these associations differ for arrivals before and after welfare reform. Late-age immigration is strongly associated with lower personal income, lower rates of Medicare and Social Security receipt, and higher participation in Supplemental Security Income (SSI) and Medicaid. Arrival after 1996 is associated with lower rates of SSI, Medicaid, and Medicare receipt. The association between late-age immigration and income is stronger for post-1996 arrivals relative to earlier arrivals, whereas that between late-age immigration and Medicaid is weaker, suggesting that the penalty conferred by late-age immigration grew after reform. Late-age immigrants face formidable economic disadvantages exacerbated by exclusion from public benefits, with implications for immigration, health care, and welfare policy. © The Author 2014. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  16. Brokering Identity and Learning Citizenship: Immigration Settlement Organizations and New Chinese Immigrants in Canada

    Science.gov (United States)

    Zhu, Yidan

    2015-01-01

    This paper examines citizenship learning and identity construction of new Chinese immigrants in a Canadian immigration settlement organization (ISO). I address the gap between the concept of "settlement" and "citizenship" generated by government-funded ISOs and new immigrants' actual practices in these programs. I adopt Dorothy…

  17. Age at Immigration and the Incomes of Older Immigrants, 1994–2010

    Science.gov (United States)

    Tienda, Marta

    2015-01-01

    Objectives. Seniors comprise a growing proportion of new U.S. immigrants. We investigate whether late-age immigrants are disadvantaged in older age relative to those arriving earlier in life, based on income, reliance on public benefits, and access to public medical insurance. We test whether the 1996 welfare reform law altered the relationships between age at immigration and these outcomes. Method. Immigrants aged 65 and older in the 1994–2010 Current Population Surveys were classified by age at immigration. Median and logistic regressions are used to estimate the association between age at immigration and several outcomes and to test whether these associations differ for arrivals before and after welfare reform. Results. Late-age immigration is strongly associated with lower personal income, lower rates of Medicare and Social Security receipt, and higher participation in Supplemental Security Income (SSI) and Medicaid. Arrival after 1996 is associated with lower rates of SSI, Medicaid, and Medicare receipt. The association between late-age immigration and income is stronger for post-1996 arrivals relative to earlier arrivals, whereas that between late-age immigration and Medicaid is weaker, suggesting that the penalty conferred by late-age immigration grew after reform. Discussion. Late-age immigrants face formidable economic disadvantages exacerbated by exclusion from public benefits, with implications for immigration, health care, and welfare policy. PMID:24942972

  18. Health Insurance Disparities among Immigrants: Are Some Legal Immigrants More Vulnerable than Others?

    Science.gov (United States)

    Pandey, Shanta; Kagotho, Njeri

    2010-01-01

    This study examined health insurance disparities among recent immigrants. The authors analyzed all working-age adult immigrants between the ages of 18 and 64 using the New Immigrant Survey data collected in 2003. This survey is a cross-sectional interview of recent legal permanent residents on their social, economic, and health status. Respondents…

  19. Dynein Light Intermediate Chain 2 Facilitates the Metaphase to Anaphase Transition by Inactivating the Spindle Assembly Checkpoint.

    Directory of Open Access Journals (Sweden)

    Sagar P Mahale

    Full Text Available The multi-functional molecular motor cytoplasmic dynein performs diverse essential roles during mitosis. The mechanistic importance of the dynein Light Intermediate Chain homologs, LIC1 and LIC2 is unappreciated, especially in the context of mitosis. LIC1 and LIC2 are believed to exist in distinct cytoplasmic dynein complexes as obligate subunits. LIC1 had earlier been reported to be required for metaphase to anaphase progression by inactivating the kinetochore-microtubule attachment-sensing arm of the spindle assembly checkpoint (SAC. However, the functional importance of LIC2 during mitosis remains elusive. Here we report prominent novel roles for the LIC2 subunit of cytoplasmic dynein in regulating the spindle assembly checkpoint. LIC2 depletion in mammalian cells led to prolonged metaphase arrest in the presence of an active SAC and also to stretched kinetochores, thus implicating it in SAC inactivation. Quantitative fluorescence microscopy of SAC components revealed accumulation of both attachment- and tension-sensing checkpoint proteins at metaphase kinetochores upon LIC2 depletion. These observations support a stronger and more diverse role in checkpoint inactivation for LIC2 in comparison to its close homolog LIC1. Our study uncovers a novel functional hierarchy during mitotic checkpoint inactivation between the closely related but homologous LIC subunits of cytoplasmic dynein. These subtle functional distinctions between dynein subpopulations could be exploited to study specific aspects of the spindle assembly checkpoint, which is a key mediator of fidelity in eukaryotic cell division.

  20. A novel ATM-dependent checkpoint defect distinct from loss of function mutation promotes genomic instability in melanoma.

    Science.gov (United States)

    Spoerri, Loredana; Brooks, Kelly; Chia, KeeMing; Grossman, Gavriel; Ellis, Jonathan J; Dahmer-Heath, Mareike; Škalamera, Dubravka; Pavey, Sandra; Burmeister, Bryan; Gabrielli, Brian

    2016-05-01

    Melanomas have high levels of genomic instability that can contribute to poor disease prognosis. Here, we report a novel defect of the ATM-dependent cell cycle checkpoint in melanoma cell lines that promotes genomic instability. In defective cells, ATM signalling to CHK2 is intact, but the cells are unable to maintain the cell cycle arrest due to elevated PLK1 driving recovery from the arrest. Reducing PLK1 activity recovered the ATM-dependent checkpoint arrest, and over-expressing PLK1 was sufficient to overcome the checkpoint arrest and increase genomic instability. Loss of the ATM-dependent checkpoint did not affect sensitivity to ionizing radiation demonstrating that this defect is distinct from ATM loss of function mutations. The checkpoint defective melanoma cell lines over-express PLK1, and a significant proportion of melanomas have high levels of PLK1 over-expression suggesting this defect is a common feature of melanomas. The inability of ATM to impose a cell cycle arrest in response to DNA damage increases genomic instability. This work also suggests that the ATM-dependent checkpoint arrest is likely to be defective in a higher proportion of cancers than previously expected. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  1. Lyn tyrosine kinase promotes silencing of ATM-dependent checkpoint signaling during recovery from DNA double-strand breaks

    International Nuclear Information System (INIS)

    Fukumoto, Yasunori; Kuki, Kazumasa; Morii, Mariko; Miura, Takahito; Honda, Takuya; Ishibashi, Kenichi; Hasegawa, Hitomi; Kubota, Sho; Ide, Yudai; Yamaguchi, Noritaka; Nakayama, Yuji; Yamaguchi, Naoto

    2014-01-01

    Highlights: • Inhibition of Src family kinases decreased γ-H2AX signal. • Inhibition of Src family increased ATM-dependent phosphorylation of Chk2 and Kap1. • shRNA-mediated knockdown of Lyn increased phosphorylation of Kap1 by ATM. • Ectopic expression of Src family kinase suppressed ATM-mediated Kap1 phosphorylation. • Src is involved in upstream signaling for inactivation of ATM signaling. - Abstract: DNA damage activates the DNA damage checkpoint and the DNA repair machinery. After initial activation of DNA damage responses, cells recover to their original states through completion of DNA repair and termination of checkpoint signaling. Currently, little is known about the process by which cells recover from the DNA damage checkpoint, a process called checkpoint recovery. Here, we show that Src family kinases promote inactivation of ataxia telangiectasia mutated (ATM)-dependent checkpoint signaling during recovery from DNA double-strand breaks. Inhibition of Src activity increased ATM-dependent phosphorylation of Chk2 and Kap1. Src inhibition increased ATM signaling both in G2 phase and during asynchronous growth. shRNA knockdown of Lyn increased ATM signaling. Src-dependent nuclear tyrosine phosphorylation suppressed ATM-mediated Kap1 phosphorylation. These results suggest that Src family kinases are involved in upstream signaling that leads to inactivation of the ATM-dependent DNA damage checkpoint

  2. Disruption of spindle checkpoint function in rats following 28 days of repeated administration of renal carcinogens.

    Science.gov (United States)

    Kimura, Masayuki; Mizukami, Sayaka; Watanabe, Yousuke; Hasegawa-Baba, Yasuko; Onda, Nobuhiko; Yoshida, Toshinori; Shibutani, Makoto

    2016-02-01

    We previously reported that 28-day exposure to hepatocarcinogens that facilitate cell proliferation specifically alters the expression of G1/S checkpoint-related genes and proteins, induces aberrant early expression of ubiquitin D (UBD) at the G2 phase, and increases apoptosis in the rat liver, indicating G1/S and spindle checkpoint dysfunction. The present study aimed to determine the time of onset of carcinogen-specific cell-cycle disruption after repeated administration of renal carcinogens for up to 28 days. Rats were orally administered the renal carcinogens nitrofurantoin (NFT), 1-amino-2,4-dibromoantraquinone (ADAQ), and 1,2,3-trichloropropane (TCP) or the non-carcinogenic renal toxicants 1-chloro-2-propanol, triamterene, and carboxin for 3, 7 or 28 days. Both immunohistochemical single-molecule analysis and real-time RT-PCR analysis revealed that carcinogen-specific expression changes were not observed after 28 days of administration. However, the renal carcinogens ADAQ and TCP specifically reduced the number of cells expressing phosphorylated-histone H3 at Ser10 in both UBD(+) cells and proliferating cells, suggestive of insufficient UBD expression at the M phase and early transition of proliferating cells from the M phase, without increasing apoptosis, after 28 days of administration. In contrast, NFT, which has marginal carcinogenic potential, did not induce such cellular responses. These results suggest that it may take 28 days to induce spindle checkpoint dysfunction by renal carcinogens; however, induction of apoptosis may not be essential. Thus, induction of spindle checkpoint dysfunction may be dependent on carcinogenic potential of carcinogen examined, and marginal carcinogens may not exert sufficient responses even after 28 days of administration.

  3. CDC28, NETI, and HFII are required for checkpoints in Saccharomyces cerevisiae

    International Nuclear Information System (INIS)

    Koltovaya, N.A.; Kadyshevskaya, E.Yu.; Roshina, M.P.; Devin, A.B.

    2009-01-01

    The involvement of SRM genes selected as genes affecting genetic stability and radiosensitivity in a cell cycle arrest under the action of damaging agents was studied. It was shown that the srm5/cdc28-srm, srm8/netI-srm, and srmI2/hfiI-srm mutations prevent checkpoint activation by DNA damage, particularly the G 0 /S (srm5, srm8), G 1 /S (srm5, srm8, srm12), S (srm8, srm12) and S/G 2 (srm5) checkpoints. It seems that in budding yeast the CDC28, HFII/ADAI, and NETI genes mediate cellular response induced by DNA damage with checkpoint control. The well-known checkpoint-genes RAD9, RAD17, RAD24, and RAD53, and the genes CDC28, and NETI have been found to belong to one epistasis group named RAD9-group as regards cell sensitivity to γ radiation. An analysis of the radiosensitivity of double mutants has revealed that the mutation cdc-28-srm is hypostatic to each of mutations rad9Δ, and rad24Δ, and additive to rad17Δ. The mutation netI-srm is hypostatic to the mutations rad9Δ but additive to rad17Δ, rad24Δ, and rad53. The mutation hfiI-srm has an additive effect in compound with the mutations rad24Δ and rad9Δ. So, investigations of epistatic interactions have demonstrated a branched RAD9-dependent pathway. The analyzed genes can also participate in a minor mechanism involved in determining cell radiation sensitivity independently of the mentioned RAD9-dependent pathway

  4. Oncogene-induced senescence is part of the tumorigenesis barrier imposed by DNA damage checkpoints

    DEFF Research Database (Denmark)

    Bartkova, Jirina; Rezaei, Nousin; Liontos, Michalis

    2006-01-01

    Recent studies have indicated the existence of tumorigenesis barriers that slow or inhibit the progression of preneoplastic lesions to neoplasia. One such barrier involves DNA replication stress, which leads to activation of the DNA damage checkpoint and thereby to apoptosis or cell cycle arrest...... and senescence markers cosegregate closely. Thus, senescence in human preneoplastic lesions is a manifestation of oncogene-induced DNA replication stress and, together with apoptosis, provides a barrier to malignant progression....

  5. SPARC: Demonstrate burst-buffer-based checkpoint/restart on ATS-1.

    Energy Technology Data Exchange (ETDEWEB)

    Oldfield, Ron A. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Ulmer, Craig D. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Widener, Patrick [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Ward, H. Lee [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2018-01-01

    Recent high-performance computing (HPC) platforms such as the Trinity Advanced Technology System (ATS-1) feature burst buffer resources that can have a dramatic impact on an application’s I/O performance. While these non-volatile memory (NVM) resources provide a new tier in the storage hierarchy, developers must find the right way to incorporate the technology into their applications in order to reap the benefits. Similar to other laboratories, Sandia is actively investigating ways in which these resources can be incorporated into our existing libraries and workflows without burdening our application developers with excessive, platform-specific details. This FY18Q1 milestone summaries our progress in adapting the Sandia Parallel Aerodynamics and Reentry Code (SPARC) in Sandia’s ATDM program to leverage Trinity’s burst buffers for checkpoint/restart operations. We investigated four different approaches with varying tradeoffs in this work: (1) simply updating job script to use stage-in/stage out burst buffer directives, (2) modifying SPARC to use LANL’s hierarchical I/O (HIO) library to store/retrieve checkpoints, (3) updating Sandia’s IOSS library to incorporate the burst buffer in all meshing I/O operations, and (4) modifying SPARC to use our Kelpie distributed memory library to store/retrieve checkpoints. Team members were successful in generating initial implementation for all four approaches, but were unable to obtain performance numbers in time for this report (reasons: initial problem sizes were not large enough to stress I/O, and SPARC refactor will require changes to our code). When we presented our work to the SPARC team, they expressed the most interest in the second and third approaches. The HIO work was favored because it is lightweight, unobtrusive, and should be portable to ATS-2. The IOSS work is seen as a long-term solution, and is favored because all I/O work (including checkpoints) can be deferred to a single library.

  6. Immigration and Health: Law, Policy, and Ethics.

    Science.gov (United States)

    Parmet, Wendy E; Sainsbury-Wong, Lorianne; Prabhu, Maya

    2017-03-01

    Immigration poses numerous challenges for health professionals and public health lawyers. This article reviews these challenges. We begin by offering some background on immigration and health and then explain some of the reasons why immigrants are less likely than natives to have health insurance. Next we turn to a discussion of some of the particular challenges relating to the health care of refugees. We conclude by analyzing and rejecting some of the arguments that are made for discriminating against immigrants with respect to the provision of public health benefits and services.

  7. Immigration Enforcement Actions: Fiscal Year 2012

    Data.gov (United States)

    Department of Homeland Security — Each year, the Department of Homeland Security (DHS) undertakes immigration enforcement actions involving hundreds of thousands of foreign nationals. These actions...

  8. Immigration Enforcement Actions: Fiscal Year 2004

    Data.gov (United States)

    Department of Homeland Security — Each year, the Department of Homeland Security (DHS) undertakes immigration enforcement actions involving hundreds of thousands of foreign nationals. These actions...

  9. Immigration Enforcement Actions: Fiscal Year 2007

    Data.gov (United States)

    Department of Homeland Security — Each year, the Department of Homeland Security (DHS) undertakes immigration enforcement actions involving hundreds of thousands of foreign nationals. These actions...

  10. Do Immigrants Affect Firm-Specific Wages?

    DEFF Research Database (Denmark)

    Malchow-Møller, Nikolaj; Munch, Jakob R.; Skaksen, Jan Rose

    2012-01-01

    We propose and test a novel effect of immigration on wages. Existing studies have focused on the wage effects that result from changes in the aggregate labour supply in a competitive labour market. We argue that if labour markets are not fully competitive, immigrants might also affect wage...... formation at the most disaggregate level – the workplace. Using linked employer-employee data, we find that an increased use of low-skilled immigrant workers has a significantly negative effect on the wages of native workers at the workplace – also when controlling for potential endogeneity of the immigrant...

  11. Media Exposure and Attitudes towards Immigrants

    Directory of Open Access Journals (Sweden)

    Álvarez-Gálvez Javier

    2014-01-01

    Full Text Available Despite evidences of the media?s infl uence on shaping the attitudes of the Spanish population towards the immigrant community, survey indicators have seldom been designed to explain the relationship between media coverage of immigrants and the attitudes of native towards this phenomenon. Using a sample of students, we examined the validity of different types of indicators used to measure the frequency of media consumption, the recall of news regarding immigration and the degree of media credibility in order to explain racist and xenophobic attitudes. Results reveal a clear association between the news media and native group attitudes towards immigration, thus demonstrating the usefulness of these indicators.

  12. Environmental and occupational exposures in immigrant health.

    Science.gov (United States)

    Eamranond, Pracha P; Hu, Howard

    2008-09-23

    Immigrants comprise vulnerable populations that are frequently exposed to a multitude of environmental and occupational hazards. The historical context behind state and federal legislation has helped to foster an environment that is particularly hostile toward caring for immigrant health. Current hazards include toxic exposures, air and noise pollution, motor vehicle accidents, crowded living and work environments with inadequate ventilation, poor sanitation, mechanical injury, among many others. Immigrants lack the appropriate training, materials, health care access, and other resources to reduce their exposure to preventable environmental and occupational health risks. This dilemma is exacerbated by current anti-immigrant sentiments, miscommunication between native and immigrant populations, and legislation denying immigrants access to publicly funded medical care. Given that current health policy has failed to address immigrant health appropriately and political impetus is lacking, efforts should also focus on alternative solutions, including organized labor. Labor unions that serve to educate workers, survey work environments, and defend worker rights will greatly alleviate and prevent the burden of disease incurred by immigrants. The nation's health will benefit from improved regulation of living and workplace environments to improve the health of immigrants, regardless of legal status.

  13. Immigration and suicidality in the young.

    Science.gov (United States)

    Bursztein Lipsicas, Cendrine; Henrik Mäkinen, Ilkka

    2010-05-01

    Little research has focused on the relation of immigration and suicidal behaviour in youth. Nevertheless, the impact of migration on the mental health of youth is an issue of increasing societal importance. This review aimed to present studies on the prevalence of suicidal behaviour in immigrant youth in various countries and to provide possible explanations for suicidal behaviour in immigrant youth, especially regarding acculturation. The review included a literature search to locate articles on the subject of suicidal behaviour in immigrant youth in the context of acculturation. Studies on suicidal behaviour in culturally diverse youth are few and most of the existing research does not differentiate ethnic minorities from immigrants. Studies on epidemiology and on specific risk factors were found regarding various immigrant youth including Hispanics in the United States, Asians in North America and Europe, as well as comparative studies between different immigrant groups in specific countries. The relation between immigration status and suicidal behaviours in youth appears to vary by ethnicity and country of settlement. Time spent in the new country as well as intergenerational communication and conflicts with parents have, in many of the studies, been related to suicidality in immigrant youth. Summing up, there is a clear and urgent need to further pursue the work in this field, to develop targeted public health interventions as well as psychosocial treatment for preventing suicide in these youth.

  14. Immigration Enforcement Actions: Fiscal Year 2008

    Data.gov (United States)

    Department of Homeland Security — Each year, the Department of Homeland Security (DHS) undertakes immigration enforcement actions involving hundreds of thousands of foreign nationals. These actions...

  15. Immigration Enforcement Actions: Fiscal Year 2010

    Data.gov (United States)

    Department of Homeland Security — Each year, the Department of Homeland Security (DHS) undertakes immigration enforcement actions involving hundreds of thousands of foreign nationals. These actions...

  16. Immigration Enforcement Actions: Fiscal Year 2011

    Data.gov (United States)

    Department of Homeland Security — Each year, the Department of Homeland Security (DHS) undertakes immigration enforcement actions involving hundreds of thousands of foreign nationals. These actions...

  17. Immigration Enforcement Actions: Fiscal Year 2006

    Data.gov (United States)

    Department of Homeland Security — Each year, the Department of Homeland Security (DHS) undertakes immigration enforcement actions involving hundreds of thousands of foreign nationals. These actions...

  18. Immigration Enforcement Actions: Fiscal Year 2009

    Data.gov (United States)

    Department of Homeland Security — Each year, the Department of Homeland Security (DHS) undertakes immigration enforcement actions involving hundreds of thousands of foreign nationals. These actions...

  19. Immigration Enforcement Actions: Fiscal Year 2005

    Data.gov (United States)

    Department of Homeland Security — Each year, the Department of Homeland Security (DHS) undertakes immigration enforcement actions involving hundreds of thousands of foreign nationals. These actions...

  20. Environmental and Occupational Exposures in Immigrant Health

    Directory of Open Access Journals (Sweden)

    Pracha P. Eamranond

    2008-01-01

    Full Text Available Immigrants comprise vulnerable populations that are frequently exposed to a multitude of environmental and occupational hazards. The historical context behind state and federal legislation has helped to foster an environment that is particularly hostile toward caring for immigrant health. Current hazards include toxic exposures, air and noise pollution, motor vehicle accidents, crowded living and work environments with inadequate ventilation, poor sanitation, mechanical injury, among many others. Immigrants lack the appropriate training, materials, health care access, and other resources to reduce their exposure to preventable environmental and occupational health risks. This dilemma is exacerbated by current anti-immigrant sentiments, miscommunication between native and immigrant populations, and legislation denying immigrants access to publicly funded medical care. Given that current health policy has failed to address immigrant health appropriately and political impetus is lacking, efforts should also focus on alternative solutions, including organized labor. Labor unions that serve to educate workers, survey work environments, and defend worker rights will greatly alleviate and prevent the burden of disease incurred by immigrants. The nation’s health will benefit from improved regulation of living and workplace environments to improve the health of immigrants, regardless of legal status.

  1. A Review of Immune Checkpoint Inhibitors for the Management of Locally Advanced or Metastatic Urothelial Carcinoma.

    Science.gov (United States)

    Hanna, Kirollos S

    2017-11-01

    Urothelial carcinoma (UC) is the second most common malignancy of the genitourinary system and the sixth most common cancer in the United States. The overall incidence of UC appears to be on the decline, but death rates have remained stable. Stage IV metastatic disease is associated with only a 5% survival rate at 5 years. Gemcitabine and cisplatin combinations or dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin are the preferred regimens for individuals with advance, metastatic disease and a good performance status and organ function. Second-line therapies in this setting are limited. During the course of 1 year, five immune checkpoint inhibitors were approved for treatment of cancers in the locally advanced or metastatic setting: atezolizumab, nivolumab, durvalumab, avelumab, and pembrolizumab. Immunotherapies have played a significant role in the treatment of various cancers and have continued to expand. It is of utmost importance that practitioners include checkpoint inhibitors as treatment options for UC. Based on the limited data, pembrolizumab and atezolizumab may be the drugs of choice, as they are supported by the most influential data to date; however, further research is warranted. Ongoing clinical trials will further assess the benefits of inducing cellular immunity in the treatment of UC. These therapies mark a new landscape in the treatment of UC. In this article, the available data on immune checkpoint inhibitors for the treatment of locally advanced or metastatic UC and their place in therapy are reviewed. © 2017 Pharmacotherapy Publications, Inc.

  2. Biological significance of the focus on DNA damage checkpoint factors remained after irradiation of ionizing radiation

    International Nuclear Information System (INIS)

    Yamauchi, Motohiro; Suzuki, Keiji

    2005-01-01

    This paper reviews recent reports on the focus formation and participation to checkpoint of (such phosphorylated (P-d) as below) ATM and H2AX, MDC1, 53BP1 and NBS1, and discusses their role in DNA damage checkpoint induction mainly around authors' studies. When the cell is irradiated by ionizing radiation, the subtype histone like H2AX is P-d and the formed focus', seen in the nucleus on immuno-fluorographic observation, represents the P-d H2AX at the damaged site of DNA. The role of P-d ATM (the product of causative gene of ataxia-telangiectasia mutation, a protein kinase) has been first shown by laser beam irradiation. Described are discussions on the roles and functions after irradiation in focus formation and DNA damage checkpoint of P-d H2AX (a specific histone product by the radiation like γ-ray as above), P-d ATM, MDC1 (a mediator of DNA damage check point protein 1), 53BP1, (a p53 binding protein) and NBS1 (the product of the causative gene of Nijmegen Breakage Syndrome). Authors have come to point out the remained focal size increase as implications of the efficient repair of damaged DNA, and the second cycled p53 accumulation, of tumor suppression. Thus evaluation of biological significance of these aspects, scarcely noted hitherto, is concluded important. (S.I.)

  3. Measures to detect and control radioactive contaminated metallurgical scrap at border checkpoints in Poland

    International Nuclear Information System (INIS)

    Smagala, G.

    1999-01-01

    The issue of radioactive contaminated metallurgical scrap has never received a high priority in Poland and in the international community. Since the dissolution of the former Soviet Union a higher attention has been given to the problem. Poland which is located between the West and East Europe has the obligation to develop and implement an effective prevention and detection system. The reasons to increase national control and detection system at the border checkpoints in Poland are to avoid the following risks: post Chernobyl contamination transports of commodities; transport of contaminated metal scrap; transfer of radioactive waste for their disposal or utilization; high risk of becoming a transit country of illicit trafficking of nuclear materials and radioactive sources. In order to avoid the above-mentioned risks, Poland initiated in 1990, a deployment of the portable radiation devices at the border checkpoints and, as of 1998, the number of installed instruments exceeded a hundred. This paper presents Poland's activities to detect contaminated scrap at its border checkpoints. (author)

  4. Immune checkpoint blockade therapy: The 2014 Tang prize in biopharmaceutical science

    Directory of Open Access Journals (Sweden)

    Ya-Shan Chen

    2015-02-01

    Full Text Available The first Tang Prize for Biopharmaceutical Science has been awarded to Prof. James P. Allison and Prof. Tasuku Honjo for their contributions leading to an entirely new way to treat cancer by blocking the molecules cytotoxic T lymphocyte-associated antigen 4 (CTLA-4 and programmed cell death protein 1 (PD-1 that turn off immune response. The treatment, called "immune checkpoint blockade therapy," has opened a new therapeutic era. Here the discoveries of the immune checkpoints and how they contribute to the maintenance of self-tolerance, as well as how to protect tissues from the excess immune responses causing damage are reviewed. The efforts made by Prof. Allison and Prof. Honjo for developing the most promising approaches to activate therapeutic antitumor immunity are also summarized. Since these certain immune checkpoint pathways appear to be one of the major mechanisms resulting in immune escape of tumors, the presence of anti-CTLA-4 and/or anti-PD-1 should contribute to removal of the inhibition signals for T cell activation. Subsequently, it will enhance specific T cell activation and, therefore, strengthen antitumor immunity.

  5. TAM receptor tyrosine kinases as emerging targets of innate immune checkpoint blockade for cancer therapy.

    Science.gov (United States)

    Akalu, Yemsratch T; Rothlin, Carla V; Ghosh, Sourav

    2017-03-01

    Cancer immunotherapy utilizing T-cell checkpoint inhibitors has shown tremendous clinical success. Yet, this mode of treatment is effective in only a subset of patients. Unresponsive patients tend to have non-T-cell-inflamed tumors that lack markers associated with the activation of adaptive anti-tumor immune responses. Notably, elimination of cancer cells by T cells is critically dependent on the optimal activity of innate immune cells. Therefore, identifying new targets that regulate innate immune cell function and promote the engagement of adaptive tumoricidal responses is likely to lead to the development of improved therapies against cancer. Here, we review the TAM receptor tyrosine kinases-TYRO3, AXL, and MERTK-as an emerging class of innate immune checkpoints that participate in key steps of anti-tumoral immunity. Namely, TAM-mediated efferocytosis, negative regulation of dendritic cell activity, and dysregulated production of chemokines collectively favor the escape of malignant cells. Hence, disabling TAM signaling may promote engagement of adaptive immunity and complement T-cell checkpoint blockade. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  6. Unique cytologic features of thyroiditis caused by immune checkpoint inhibitor therapy for malignant melanoma

    Directory of Open Access Journals (Sweden)

    Trevor E. Angell

    2018-03-01

    Full Text Available Blockade of immune checkpoint molecules to reverse cancer-induced immune suppression can improve anti-tumor immune responses in cancer patients. Monoclonal antibodies targeting two such molecules, Programmed cell death protein 1 (PD-1 and cytotoxic T-lymphocyte associated protein 4 (CTLA-4 have shown clinical benefit in the treatment of advanced malignancies, including metastatic melanoma. Adverse effects of these immune checkpoint inhibitors include immune-related adverse events (irAE, of which one of the most common is autoimmune thyroiditis. Though thyroiditis is increasingly recognized, there are no reports of the pathological findings that occur in immunotherapy-induced thyroiditis. We present a case of immunotherapy-induced thyroiditis demonstrating its unique cytopathologic features. A 51-year-old woman with metastatic melanoma was found to have a suppressed TSH and elevated free thyroxine concentration 14 days after starting treatment with nivolumab (PD-1 antagonist plus ipilimumab (CTLA-4 antagonist therapy. A thyroid biopsy was performed based on ultrasound findings and cytopathology revealed unique features including abundant clusters of necrotic cells, lymphocytes and CD163-positive histiocytes. This case reports cytopathologic features found in immune checkpoint inhibitor related thyroiditis. These appear to be unique findings and may help inform future research regarding the pathophysiology and mechanisms of this condition.

  7. Cdk2 is required for p53-independent G2/M checkpoint control.

    Directory of Open Access Journals (Sweden)

    Jon H Chung

    2010-02-01

    Full Text Available The activation of phase-specific cyclin-dependent kinases (Cdks is associated with ordered cell cycle transitions. Among the mammalian Cdks, only Cdk1 is essential for somatic cell proliferation. Cdk1 can apparently substitute for Cdk2, Cdk4, and Cdk6, which are individually dispensable in mice. It is unclear if all functions of non-essential Cdks are fully redundant with Cdk1. Using a genetic approach, we show that Cdk2, the S-phase Cdk, uniquely controls the G(2/M checkpoint that prevents cells with damaged DNA from initiating mitosis. CDK2-nullizygous human cells exposed to ionizing radiation failed to exclude Cdk1 from the nucleus and exhibited a marked defect in G(2/M arrest that was unmasked by the disruption of P53. The DNA replication licensing protein Cdc6, which is normally stabilized by Cdk2, was physically associated with the checkpoint regulator ATR and was required for efficient ATR-Chk1-Cdc25A signaling. These findings demonstrate that Cdk2 maintains a balance of S-phase regulatory proteins and thereby coordinates subsequent p53-independent G(2/M checkpoint activation.

  8. Loss of p53 induces M-phase retardation following G2 DNA damage checkpoint abrogation.

    Science.gov (United States)

    Minemoto, Yuzuru; Uchida, Sanae; Ohtsubo, Motoaki; Shimura, Mari; Sasagawa, Toshiyuki; Hirata, Masato; Nakagama, Hitoshi; Ishizaka, Yukihito; Yamashita, Katsumi

    2003-04-01

    Most cell lines that lack functional p53 protein are arrested in the G2 phase of the cell cycle due to DNA damage. When the G2 checkpoint is abrogated, these cells are forced into mitotic catastrophe. A549 lung adenocarcinoma cells, in which p53 was eliminated with the HPV16 E6 gene, exhibited efficient arrest in the G2 phase when treated with adriamycin. Administration of caffeine to G2-arrested cells induced a drastic change in cell phenotype, the nature of which depended on the status of p53. Flow cytometric and microscopic observations revealed that cells that either contained or lacked p53 resumed their cell cycles and entered mitosis upon caffeine treatment. However, transit to the M phase was slower in p53-negative cells than in p53-positive cells. Consistent with these observations, CDK1 activity was maintained at high levels, along with stable cyclin B1, in p53-negative cells. The addition of butyrolactone I, which is an inhibitor of CDK1 and CDK2, to the p53-negative cells reduced the floating round cell population and induced the disappearance of cyclin B1. These results suggest a relationship between the p53 pathway and the ubiquitin-mediated degradation of mitotic cyclins and possible cross-talk between the G2-DNA damage checkpoint and the mitotic checkpoint.

  9. Immune checkpoint inhibitors: the new frontier in non–small cell lung cancer treatment

    Directory of Open Access Journals (Sweden)

    El-Osta HE

    2016-08-01

    Full Text Available Hazem El-Osta, Kamran Shahid, Glenn M Mills, Prakash Peddi Department of Medicine, Division of Hematology-Oncology, Louisiana State University Health Sciences Center, Shreveport, LA, USA Abstract: Lung cancer is the major cause for cancer-related death in the US. Although advances in chemotherapy and targeted therapy have improved the outcome of metastatic non-small-cell lung cancer, its prognosis remains dismal. A deeper understanding of the complex interaction between the immune system and tumor microenvironment has identified immune checkpoint inhibitors as new avenue of immunotherapy. Rather than acting directly on the tumor, these therapies work by removing the inhibition exerted by tumor cell or other immune cells on the immune system, promoting antitumoral immune response. To date, two programmed death-1 inhibitors, namely nivolumab and pembrolizumab, have received the US Food and Drug Administration approval for the treatment of advanced non-small-cell lung cancer that failed platinum-based chemotherapy. This manuscript provides a brief overview of the pathophysiology of cancer immune evasion, summarizes pertinent data on completed and ongoing clinical trials involving checkpoint inhibitors, discusses the different strategies to optimize their function, and outlines various challenges that are faced in this promising yet evolving field. Keywords: checkpoint inhibitors, immunotherapy, nivolumab, non-small-cell lung cancer, pembrolizumab, programmed death-1, programmed death ligand-1

  10. USCIS Applications for Immigration Benefits and Naturalization Monthly Statistical Reports

    Data.gov (United States)

    Department of Homeland Security — The 'Application for Immigration Benefits' monthly charts provide data on applications and petitions received by USCIS for immigration benefits. The report exclude...

  11. The Illegal Immigration Reform and Immigrant Responsibility Act of 1996: an overview.

    Science.gov (United States)

    Fragomen, A T

    1997-01-01

    "On September 30, 1996, President Clinton signed the Illegal Immigration Reform and Immigrant Responsibility Act of 1996 (1996 Act), Pub. L. No. 104-208, 110 Stat. 3009. After an intense lobbying effort by the business community, most provisions relating to legal immigration were omitted from the final bill. Instead, the 1996 Act focuses on illegal immigration reform and includes some of the toughest measures ever taken against illegal immigration." Aspects considered include border enforcement, penalities against alien smuggling and document fraud, deportation and exclusion proceedings, employer sanctions, welfare provisions, and changes to existing refugee and asylum procedures. excerpt

  12. „I do not mind immigrants, it is immigration that bothers me“: The inconsistency of immigration attitudes in Europe

    Czech Academy of Sciences Publication Activity Database

    Čermáková, Dita; Leontiyeva, Yana

    2017-01-01

    Roč. 122, č. 4 (2017), s. 500-525 ISSN 1212-0014 Institutional support: RVO:68378025 Keywords : immigration * attitudes towards immigrants in Europe * personalized and general attitudes Subject RIV: AO - Sociology, Demography OBOR OECD: Sociology Impact factor: 0.580, year: 2016

  13. The complexity and ambivalence of immigration attitudes: ambivalent stereotypes predict conflicting attitudes toward immigration policies.

    Science.gov (United States)

    Reyna, Christine; Dobria, Ovidiu; Wetherell, Geoffrey

    2013-07-01

    Americans' conflicted attitudes toward immigrants and immigration has stymied immigration reform for decades. In this article, we explore the nuanced nature of stereotypes about immigrants and how they relate to ambivalent attitudes toward immigrant groups and the disparate array of immigration policies that affect them. Using item response theory and multiple regression analysis, we identified and related stereotypes of different immigrant groups to group-based and policy attitudes. Results demonstrate that ambivalent stereotypes mapped onto ambivalent group-based and immigration policy attitudes. Specifically, stereotypes that portray groups in positive or sympathetic ways predicted positive attitudes toward the group and more supportive attitudes toward policies that facilitate their immigration to the United States. Conversely, negative qualities predicted negative attitudes toward the same group and support for policies that prevent the group from immigrating. Results are discussed in light of current theory related to stereotype content, complementarity of stereotypes, and broader implications for immigration attitudes and policy. PsycINFO Database Record (c) 2013 APA, all rights reserved.

  14. Determinants of Recent Immigrants' Location Choices

    DEFF Research Database (Denmark)

    Damm, Anna Piil

    This paper exploits a Danish spatial dispersal policy on refugees which can be regarded a natural experiment to investigate the influence of regional factors on recent immigrants' locational choices. The main push factors are lack of co-ethnics and presence of immigrants. Additional push factors...

  15. The Digital Biliteracies of Arab Immigrant Mothers

    Science.gov (United States)

    Al-Salmi, Laila Z.; Smith, Patrick H.

    2015-01-01

    Few studies have explored how the literacies of immigrant parents are influenced by participation in their children's emerging biliteracy. This study addressed this lacuna using a qualitative case study design to investigate the biliteracy development of Arab immigrant mothers in the U.S. Southwest. We used the framework of digital biliteracy to…

  16. Academic Trajectories of Newcomer Immigrant Youth

    Science.gov (United States)

    Suarez-Orozco, Carola; Gaytan, Francisco X.; Bang, Hee Jin; Pakes, Juliana; O'Connor, Erin; Rhodes, Jean

    2010-01-01

    Immigration to the United States presents both challenges and opportunities that affect students' academic achievement. Using a 5-year longitudinal, mixed-methods approach, we identified varying academic trajectories of newcomer immigrant students from Central America, China, the Dominican Republic, Haiti, and Mexico. Latent class growth curve…

  17. Children of Immigration. The Developing Child Series.

    Science.gov (United States)

    Suarez-Orozco, Carola; Suarez-Orozco, Marcelo M.

    This book offers an interdisciplinary perspective on who the children of immigrants are, considering historical and contemporary social attitudes, opportunities, and barriers they encounter. It examines the psychosocial experiences of immigration and considers how these factors interact in ways that lead to divergent pathways of adaptation and…

  18. Reducing Income Transfers to Refugee Immigrants

    DEFF Research Database (Denmark)

    Rosholm, Michael; Vejlin, Rune Majlund

    2010-01-01

    We estimate the effect of lowering income transfers to refugee immigrants in Denmark - labeled start-help - using a competing risk framework. Refugee immigrants obtaining residence permit before July 2002 received larger income transfers than those who obtained their residence permit later...

  19. How not to argue about immigration

    Directory of Open Access Journals (Sweden)

    Corlett Angelo J.

    2013-01-01

    Full Text Available This paper describes and assesses the arguments offered both against closed borders and in favor of a more open borders approach to U.S. immigration reform as those arguments are set forth in R. Pevnick’s book, Immigration and the Constraints of Justice. We find numerous problems with Pevnick’s reasoning on both counts.

  20. Neighborhood Context and Immigrant Young Children's Development

    Science.gov (United States)

    Leventhal, Tama; Shuey, Elizabeth A.

    2014-01-01

    This study explored how neighborhood social processes and resources, relevant to immigrant families and immigrant neighborhoods, contribute to young children's behavioral functioning and achievement across diverse racial/ethnic groups. Data were drawn from the Project on Human Development in Chicago Neighborhoods, a neighborhood-based,…

  1. Second-Language Literacy, Immigration, and Globalization

    Science.gov (United States)

    Soto Huerta, M. E.; Pérez, B.

    2015-01-01

    Second language literacy development is a significant factor influencing immigrants' opportunities to integrate with the host society. To examine the opportunities that different immigrant groups have had for obtaining both, we selected four published studies that had been originally analyzed through a sociocultural perspective, a prominent…

  2. Prejudices against Immigrants in Secondary School

    Science.gov (United States)

    Etxeberria, Felix; Murua, Hilario; Arrieta, Elisabet; Garmendia, Joxe; Etxeberria, Juan

    2015-01-01

    This paper presents the results of a study of prejudice against immigrants in secondary schools in the Basque Country, in Spain. We carried out a review of the best-known questionnaires and catalogues on prejudices regarding immigration and we drew up a new questionnaire, with positive and negative scales of prejudices, in order to apply them to…

  3. Occupational adjustment of immigrants in the Netherlands

    NARCIS (Netherlands)

    Zorlu, A.

    2013-01-01

    This article examines the speed of the occupational adjustment of immigrants using Labour Force Surveys 2004 and 2005 from Statistics Netherlands. The analysis provides new evidence that immigrants start with jobs at the lower levels of skill distribution. Their occupational achievement improves

  4. Immigration Enforcement Within the United States

    Science.gov (United States)

    2006-04-06

    Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 Policy Issues...Remained in the United States, (Washington: Center for Immigration Studies, May 2002). Immigration Enforcement Within the United States Introduction ...interior enforcement lack a border component. For example, fugitive taskforces, investigations of alien slavery and sweatshops , and employer sanctions do

  5. Connecting the Immigrant Experience through Literature

    Science.gov (United States)

    Allen, Eliza G.

    2016-01-01

    A 3rd-grade teacher used literature to help her immigrant students grapple with some of the larger issues related to immigration. Through the story of one Latino student, the teacher shares the literature that she used and how one student responded.

  6. Marriage strategies among immigrants in Spain

    NARCIS (Netherlands)

    Sánchez-Domínguez, M.; de Valk, H.A.G.; Reher, D.S.

    2011-01-01

    This paper studies patterns of endogamous marriages of immigrants in Spain by using data from the National Immigrant Survey of Spain (2007). First of all, we examine patterns of endogamous marriage and links between migration and marriage. Second, we assess the factors influencing the likelihood of

  7. Membership Contests: Encountering Immigrant Youth in Finland

    Science.gov (United States)

    Harinen, Paivi; Suurpaa, Leena; Hoikkala, Tommi; Hautaniemi, Petri; Perho, Sini; Keskisalo, Anne-Mari; Kuure, Tapio; Kunnapuu, Krista

    2005-01-01

    This article discusses different aspects of social and societal membership, when minority groups of young immigrants living in Finland are under consideration. During its history, Finland has mainly been a country of emigration. In the 1990s the direction of moving turned to the contrary and the amount of immigrants in Finland increased relatively…

  8. K-12 educational outcomes of immigrant youth.

    Science.gov (United States)

    Crosnoe, Robert; Turley, Ruth N López

    2011-01-01

    The children from immigrant families in the United States make up a historically diverse population, and they are demonstrating just as much diversity in their experiences in the K-12 educational system. Robert Crosnoe and Ruth López Turley summarize these K-12 patterns, paying special attention to differences in academic functioning across segments of the immigrant population defined by generational status, race and ethnicity, and national origin. A good deal of evidence points to an immigrant advantage in multiple indicators of academic progress, meaning that many youths from immigrant families outperform their peers in school. This apparent advantage is often referred to as the immigrant paradox, in that it occurs despite higher-than-average rates of social and economic disadvantages in this population as a whole. The immigrant paradox, however, is more pronounced among the children of Asian and African immigrants than other groups, and it is stronger for boys than for girls. Furthermore, evidence for the paradox is far more consistent in secondary school than in elementary school. Indeed, school readiness appears to be one area of potential risk for children from immigrant families, especially those of Mexican origin. For many groups, including those from Latin America, any evidence of the immigrant paradox usually emerges after researchers control for family socioeconomic circumstances and youths' English language skills. For others, including those from Asian countries, it is at least partially explained by the tendency for more socioeconomically advantaged residents of those regions to leave their home country for the United States. Bilingualism and strong family ties help to explain immigrant advantages in schooling; school, community, and other contextual disadvantages may suppress these advantages or lead to immigrant risks. Crosnoe and Turley also discuss several policy efforts targeting young people from immigrant families, especially those of Latin

  9. K–12 Educational Outcomes of Immigrant Youth

    Science.gov (United States)

    Crosnoe, Robert; López Turley, Ruth N.

    2017-01-01

    Summary The children from immigrant families in the United States make up a historically diverse population, and they are demonstrating just as much diversity in their experiences in the K–12 educational system. Robert Crosnoe and Ruth López Turley summarize these K–12 patterns, paying special attention to differences in academic functioning across segments of the immigrant population defined by generational status, race and ethnicity, and national origin. A good deal of evidence points to an immigrant advantage in multiple indicators of academic progress, meaning that many youths from immigrant families outperform their peers in school. This apparent advantage is often referred to as the immigrant paradox, in that it occurs despite higher-than-average rates of social and economic disadvantages in this population as a whole. The immigrant paradox, however, is more pronounced among the children of Asian and African immigrants than other groups, and it is stronger for boys than for girls. Furthermore, evidence for the paradox is far more consistent in secondary school than in elementary school. Indeed, school readiness appears to be one area of potential risk for children from immigrant families, especially those of Mexican origin. For many groups, including those from Latin America, any evidence of the immigrant paradox usually emerges after researchers control for family socioeconomic circumstances and youths’ English language skills. For others, including those from Asian countries, it is at least partially explained by the tendency for more socioeconomically advantaged residents of those regions to leave their home country for the United States. Bilingualism and strong family ties help to explain immigrant advantages in schooling; school, community, and other contextual disadvantages may suppress these advantages or lead to immigrant risks. Crosnoe and Turley also discuss several policy efforts targeting young people from immigrant families, especially

  10. The Contributions of Immigrants to American Culture.

    Science.gov (United States)

    Hirschman, Charles

    2013-01-01

    The standard account of American immigration focuses on the acculturation and assimilation of immigrants and their children to American society. This analysis typically ignores the significant contributions of immigrants to the creation of American culture through the performing arts, sciences, and other cultural pursuits. Immigrants and their children are not born with more creative talents than native-born citizens, but their selectivity and marginality may have pushed and pulled those with ability into high-risk career paths that reward creative work. The presence of large numbers of talented immigrants in Hollywood, academia, and the high-tech industries has pushed American institutions to be more meritocratic and open to innovation than they would be otherwise.

  11. Festival Foods in the Immigrant Diet

    Science.gov (United States)

    Azar, Kristen M.J.; Chen, Edith; Holland, Ariel T.; Palaniappan, Latha P.

    2012-01-01

    Dietary acculturation for immigrant groups has largely been attributed to the “Westernization” of indigenous diets, as characterized by an increased consumption of unhealthy American foods (i.e. fast foods, hamburgers). However, acculturation and adoption of western dietary habits may not fully explain new dietary patterns among racial/ethnic minority immigrants. The immigrant diet may change in such a way that it elaborates on specific ethnic traditions in addition to the incorporation of Western food habits. In this paper, we explore the role that festival foods, those foods that were once eaten a few times a year and on special occasions, play in the regular diet of immigrants to the U.S. This paper will focus on the overconsumption of ethnic festival foods, which are often high in carbohydrates, animal protein, sugar and fat, as opposed to Western “junk” food, as an explanation for the increased risk of cardiometabolic disorders among new immigrant groups. PMID:22968231

  12. Immigration as a social determinant of health.

    Science.gov (United States)

    Castañeda, Heide; Holmes, Seth M; Madrigal, Daniel S; Young, Maria-Elena DeTrinidad; Beyeler, Naomi; Quesada, James

    2015-03-18

    Although immigration and immigrant populations have become increasingly important foci in public health research and practice, a social determinants of health approach has seldom been applied in this area. Global patterns of morbidity and mortality follow inequities rooted in societal, political, and economic conditions produced and reproduced by social structures, policies, and institutions. The lack of dialogue between these two profoundly related phenomena-social determinants of health and immigration-has resulted in missed opportunities for public health research, practice, and policy work. In this article, we discuss primary frameworks used in recent public health literature on the health of immigrant populations, note gaps in this literature, and argue for a broader examination of immigration as both socially determined and a social determinant of health. We discuss priorities for future research and policy to understand more fully and respond appropriately to the health of the populations affected by this global phenomenon.

  13. Association between Integration Policies and Immigrants' Mortality

    DEFF Research Database (Denmark)

    Ikram, Umar Z; Malmusi, Davide; Juel, Knud

    2015-01-01

    BACKGROUND: To integrate immigrants into their societies, European countries have adopted different types of policies, which may influence health through both material and psychosocial determinants. Recent studies have suggested poorer health outcomes for immigrants living in countries with poorly...... confounders and data comparability issues (e.g., French cross-sectional data) may affect the findings, this study suggests that different macro-level policy contexts may influence immigrants' mortality. Comparable mortality registration systems across Europe along with detailed socio-demographic information...... with their peers in the Netherlands, Turkish-born immigrants had higher all-cause mortality in Denmark (MRR men 1.92; 95% CI 1.74-2.13 and women 2.11; 1.80-2.47) but lower in France (men 0.64; 0.59-0.69 and women 0.58; 0.51-0.67). A similar pattern emerged for Moroccan-born immigrants. The relative differences...

  14. Economic Assimilation and Outmigration of Immigrants in West-Germany

    NARCIS (Netherlands)

    Bellemare, C.

    2003-01-01

    By analyzing earnings of observed immigrants workers, the literature on the economic assimilation of immigrants has generally overlooked two potentially important selectivity issues.First, earnings of immigrant workers may di¿er substantially from those of non-workers.Second, earnings of immigrants

  15. Skill-based immigration, economic integration, and economic performance

    OpenAIRE

    Aydemir, Abdurrahman

    2014-01-01

    Studies for major immigrant-receiving countries provide evidence on the comparative economic performance of immigrant classes (skill-, kinship-, and humanitarian-based). Developed countries are increasingly competing for high-skilled immigrants, who perform better in the labor market. However, there are serious challenges to their economic integration, which highlights a need for complementary immigration and integration policies.

  16. Credible Immigration Policy Reform: A Response to Briggs

    Science.gov (United States)

    Orrenius, Pia M.; Zavodny, Madeline

    2012-01-01

    The authors agree with Vernon M. Briggs, Jr., that U.S. immigration policy has had unexpected consequences. The 1965 immigration reforms led to unanticipated chain migration from developing countries whereas the 1986 Immigration Reform and Control Act failed to slow unauthorized immigration. The result is a large foreign-born population with…

  17. 8 CFR 1003.11 - Administrative control Immigration Courts.

    Science.gov (United States)

    2010-01-01

    ... 8 Aliens and Nationality 1 2010-01-01 2010-01-01 false Administrative control Immigration Courts. 1003.11 Section 1003.11 Aliens and Nationality EXECUTIVE OFFICE FOR IMMIGRATION REVIEW, DEPARTMENT OF JUSTICE GENERAL PROVISIONS EXECUTIVE OFFICE FOR IMMIGRATION REVIEW Office of the Chief Immigration Judge...

  18. 8 CFR 1235.6 - Referral to immigration judge.

    Science.gov (United States)

    2010-01-01

    ... 8 Aliens and Nationality 1 2010-01-01 2010-01-01 false Referral to immigration judge. 1235.6 Section 1235.6 Aliens and Nationality EXECUTIVE OFFICE FOR IMMIGRATION REVIEW, DEPARTMENT OF JUSTICE IMMIGRATION REGULATIONS INSPECTION OF PERSONS APPLYING FOR ADMISSION § 1235.6 Referral to immigration judge...

  19. 28 CFR 0.116 - Board of Immigration Appeals.

    Science.gov (United States)

    2010-07-01

    ... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Board of Immigration Appeals. 0.116 Section 0.116 Judicial Administration DEPARTMENT OF JUSTICE ORGANIZATION OF THE DEPARTMENT OF JUSTICE Executive Office for Immigration Review § 0.116 Board of Immigration Appeals. The Board of Immigration...

  20. 8 CFR 1299.2 - Specific immigration review forms.

    Science.gov (United States)

    2010-01-01

    ... 8 Aliens and Nationality 1 2010-01-01 2010-01-01 false Specific immigration review forms. 1299.2 Section 1299.2 Aliens and Nationality EXECUTIVE OFFICE FOR IMMIGRATION REVIEW, DEPARTMENT OF JUSTICE NATIONALITY REGULATIONS IMMIGRATION REVIEW FORMS § 1299.2 Specific immigration review forms. The Director of...

  1. 8 CFR 1299.1 - Use of immigration forms.

    Science.gov (United States)

    2010-01-01

    ... 8 Aliens and Nationality 1 2010-01-01 2010-01-01 false Use of immigration forms. 1299.1 Section 1299.1 Aliens and Nationality EXECUTIVE OFFICE FOR IMMIGRATION REVIEW, DEPARTMENT OF JUSTICE NATIONALITY REGULATIONS IMMIGRATION REVIEW FORMS § 1299.1 Use of immigration forms. In addition to forms...

  2. 22 CFR 42.31 - Family-sponsored immigrants.

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Family-sponsored immigrants. 42.31 Section 42.31 Foreign Relations DEPARTMENT OF STATE VISAS VISAS: DOCUMENTATION OF IMMIGRANTS UNDER THE IMMIGRATION AND NATIONALITY ACT, AS AMENDED Immigrants Subject to Numerical Limitations § 42.31 Family...

  3. 22 CFR 40.71 - Documentation requirements for immigrants.

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Documentation requirements for immigrants. 40... NONIMMIGRANTS AND IMMIGRANTS UNDER THE IMMIGRATION AND NATIONALITY ACT, AS AMENDED Documentation Requirements § 40.71 Documentation requirements for immigrants. INA 212(a)(7)(A) is not applicable at the time of...

  4. Fully Realizing the Civic Potential of Immigrant Youth

    Science.gov (United States)

    Callahan, Rebecca M.; Obenchain, Kathryn M.

    2018-01-01

    Over the course of a few cold days last February, immigrant families and their allies in Austin, Texas, were shaken by a series of raids as immigration officers descended upon the city. After all was said and done, Immigration and Customs Enforcement (ICE) officials arrested 51 undocumented immigrants, most of whom had no criminal record. In this…

  5. Population Pressures Abroad and Immigration Pressures at Home.

    Science.gov (United States)

    Population Crisis Committee, Washington, DC.

    This report discusses population trends abroad and their relation to immigration pressures and policies in the United States. The following sections are included: (1) "Two Major Waves of Immigration"; (2) "The U.S.--A Major Host Nation for Permanent Immigrants"; (3) "Changing Sources of Immigrants to the United…

  6. Immigration within European Union – Does health immigration make a difference in analgesic use?

    Directory of Open Access Journals (Sweden)

    Airaksinen M.

    2006-12-01

    Full Text Available European integration has facilitated the emigration inside Europe and it has been predicted that the amount of immigrants in Southern European countries will increase in the future. As these people age and their morbidity increases, they will demand more services from local health care than immigrants do at the moment. The aim of this study is to determine the amount of Finnish people who have moved to Spain for health reasons (health immigrants and whether their health service and analgesic usage patterns differed from those of non-health immigrants. Methods: This study was carried out among Finnish people living in Costa del Sol area, southern Spain. The data were collected by questionnaire during 2002 by using a convenience sample of 1,000 Finns living permanently in the area (response rate 53%, n=530. Statistical analyses were conducted using statistical software SPSS 11.5.Results: Two-thirds of the respondents were categorised as health immigrants. Health immigrants were more often suffering from chronic morbidity, their perceived health status was poorer and they used public health services more often than the non-health immigrants. Half (50% of the all respondents had used some analgesics during the two weeks before the survey. There were more analgesic users among the health immigrant group (54 % vs. 43 %, p = 0.034 and they also used analgesics more frequently than the non-health immigrants (27 % vs. 9 %, p= 0.020. Conclusions: Our study indicates, that high amount of Finnish immigrants suffer from some degree of health problems and the health state factors have a large influence on the emigration into Spain. As this kind of trend might also exist among immigrants from other EU-nations, immigrants might burden the local Spanish health care services in the future. Therefore the Providers of health care services in immigrant areas should consider these trends in planning health care in the future.

  7. Dpb11/TopBP1 plays distinct roles in DNA replication, checkpoint response and homologous recombination

    DEFF Research Database (Denmark)

    Germann, Susanne Manuela; Østergaard, Vibe Hallundbæk; Haas, Caroline

    2011-01-01

    DPB11/TopBP1 is an essential evolutionarily conserved gene involved in initiation of DNA replication and checkpoint signaling. Here, we show that Saccharomyces cerevisiae Dpb11 forms nuclear foci that localize to sites of DNA damage in G1, S and G2 phase, a recruitment that is conserved for its...... and Tel1, and of the checkpoint mediator Rad9. In a site-directed mutagenesis screen, we identify a separation-of-function mutant, dpb11-PF, that is sensitive to DSB-inducing agents yet remains proficient for DNA replication and the S-phase checkpoint at the permissive temperature. The dpb11-PF mutant...... homologue TopBP1 in Gallus gallus. Damage-induced Dpb11 foci are distinct from Sld3 replication initiation foci. Further, Dpb11 foci are dependent on the checkpoint proteins Mec3 (9-1-1 complex) and Rad24, and require the C-terminal domain of Dpb11. Dpb11 foci are independent of the checkpoint kinases Mec1...

  8. Drosophila MOF controls Checkpoint protein2 and regulates genomic stability during early embryogenesis.

    Science.gov (United States)

    Pushpavalli, Sreerangam N C V L; Sarkar, Arpita; Ramaiah, M Janaki; Chowdhury, Debabani Roy; Bhadra, Utpal; Pal-Bhadra, Manika

    2013-01-24

    In Drosophila embryos, checkpoints maintain genome stability by delaying cell cycle progression that allows time for damage repair or to complete DNA synthesis. Drosophila MOF, a member of MYST histone acetyl transferase is an essential component of male X hyperactivation process. Until recently its involvement in G2/M cell cycle arrest and defects in ionizing radiation induced DNA damage pathways was not well established. Drosophila MOF is highly expressed during early embryogenesis. In the present study we show that haplo-insufficiency of maternal MOF leads to spontaneous mitotic defects like mitotic asynchrony, mitotic catastrophe and chromatid bridges in the syncytial embryos. Such abnormal nuclei are eliminated and digested in the yolk tissues by nuclear fall out mechanism. MOF negatively regulates Drosophila checkpoint kinase 2 tumor suppressor homologue. In response to DNA damage the checkpoint gene Chk2 (Drosophila mnk) is activated in the mof mutants, there by causing centrosomal inactivation suggesting its role in response to genotoxic stress. A drastic decrease in the fall out nuclei in the syncytial embryos derived from mof¹/+; mnkp⁶/+ females further confirms the role of DNA damage response gene Chk2 to ensure the removal of abnormal nuclei from the embryonic precursor pool and maintain genome stability. The fact that mof mutants undergo DNA damage has been further elucidated by the increased number of single and double stranded DNA breaks. mof mutants exhibited genomic instability as evidenced by the occurance of frequent mitotic bridges in anaphase, asynchronous nuclear divisions, disruption of cytoskeleton, inactivation of centrosomes finally leading to DNA damage. Our findings are consistent to what has been reported earlier in mammals that; reduced levels of MOF resulted in increased genomic instability while total loss resulted in lethality. The study can be further extended using Drosophila as model system and carry out the interaction of MOF

  9. Drosophila MOF controls Checkpoint protein2 and regulates genomic stability during early embryogenesis

    Directory of Open Access Journals (Sweden)

    Pushpavalli Sreerangam NCVL

    2013-01-01

    Full Text Available Abstract Background In Drosophila embryos, checkpoints maintain genome stability by delaying cell cycle progression that allows time for damage repair or to complete DNA synthesis. Drosophila MOF, a member of MYST histone acetyl transferase is an essential component of male X hyperactivation process. Until recently its involvement in G2/M cell cycle arrest and defects in ionizing radiation induced DNA damage pathways was not well established. Results Drosophila MOF is highly expressed during early embryogenesis. In the present study we show that haplo-insufficiency of maternal MOF leads to spontaneous mitotic defects like mitotic asynchrony, mitotic catastrophe and chromatid bridges in the syncytial embryos. Such abnormal nuclei are eliminated and digested in the yolk tissues by nuclear fall out mechanism. MOF negatively regulates Drosophila checkpoint kinase 2 tumor suppressor homologue. In response to DNA damage the checkpoint gene Chk2 (Drosophila mnk is activated in the mof mutants, there by causing centrosomal inactivation suggesting its role in response to genotoxic stress. A drastic decrease in the fall out nuclei in the syncytial embryos derived from mof1/+; mnkp6/+ females further confirms the role of DNA damage response gene Chk2 to ensure the removal of abnormal nuclei from the embryonic precursor pool and maintain genome stability. The fact that mof mutants undergo DNA damage has been further elucidated by the increased number of single and double stranded DNA breaks. Conclusion mof mutants exhibited genomic instability as evidenced by the occurance of frequent mitotic bridges in anaphase, asynchronous nuclear divisions, disruption of cytoskeleton, inactivation of centrosomes finally leading to DNA damage. Our findings are consistent to what has been reported earlier in mammals that; reduced levels of MOF resulted in increased genomic instability while total loss resulted in lethality. The study can be further extended using

  10. T cells in chronic lymphocytic leukemia display dysregulated expression of immune checkpoints and activation markers.

    Science.gov (United States)

    Palma, Marzia; Gentilcore, Giusy; Heimersson, Kia; Mozaffari, Fariba; Näsman-Glaser, Barbro; Young, Emma; Rosenquist, Richard; Hansson, Lotta; Österborg, Anders; Mellstedt, Håkan

    2017-03-01

    Chronic lymphocytic leukemia is characterized by impaired immune functions largely due to profound T-cell defects. T-cell functions also depend on co-signaling receptors, inhibitory or stimulatory, known as immune checkpoints, including cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) and programmed death-1 (PD-1). Here we analyzed the T-cell phenotype focusing on immune checkpoints and activation markers in chronic lymphocytic leukemia patients (n=80) with different clinical characteristics and compared them to healthy controls. In general, patients had higher absolute numbers of CD3 + cells and the CD8 + subset was particularly expanded in previously treated patients. Progressive patients had higher numbers of CD4 + and CD8 + cells expressing PD-1 compared to healthy controls, which was more pronounced in previously treated patients ( P =0.0003 and P =0.001, respectively). A significant increase in antigen-experienced T cells was observed in patients within both the CD4 + and CD8 + subsets, with a significantly higher PD-1 expression. Higher numbers of CD4 + and CD8 + cells with intracellular CTLA-4 were observed in patients, as well as high numbers of proliferating (Ki67 + ) and activated (CD69 + ) CD4 + and CD8 + cells, more pronounced in patients with active disease. The numbers of Th1, Th2, Th17 and regulatory T cells were substantially increased in patients compared to controls ( P leukemia T cells display increased expression of immune checkpoints, abnormal subset distribution, and a higher proportion of proliferating cells compared to healthy T cells. Disease activity and previous treatment shape the T-cell profile of chronic lymphocytic leukemia patients in different ways. Copyright© Ferrata Storti Foundation.

  11. Checkpoint Inhibition: Programmed Cell Death 1 and Programmed Cell Death 1 Ligand Inhibitors in Hodgkin Lymphoma.

    Science.gov (United States)

    Villasboas, Jose Caetano; Ansell, Stephen

    2016-01-01

    Hodgkin lymphoma (HL) is a lymphoid malignancy characterized by a reactive immune infiltrate surrounding relatively few malignant cells. In this scenario, active immune evasion seems to play a central role in allowing tumor progression. Immune checkpoint inhibitor pathways are normal mechanisms of T-cell regulation that suppress immune effector function following an antigenic challenge. Hodgkin lymphoma cells are able to escape immune surveillance by co-opting these mechanisms. The programmed cell death 1 (PD-1) pathway in particular is exploited in HL as the malignant Hodgkin and Reed-Sternberg cells express on their surface cognate ligands (PD-L1/L2) for the PD-1 receptor and thereby dampen the T-cell-mediated antitumoral response. Monoclonal antibodies that interact with and disrupt the PD-1:PD-L1/L2 axis have now been developed and tested in early-phase clinical trials in patients with advanced HL with encouraging results. The remarkable clinical activity of PD-1 inhibitors in HL highlights the importance of immune checkpoint pathways as therapeutic targets in HL. In this review, we discuss the rationale for targeting PD-1 and PD-L1 in the treatment of HL. We will evaluate the published clinical data on the different agents and highlight the safety profile of this class of agents. We discuss the available evidence on the use of biomarkers as predictors of response to checkpoint blockade and summarize the areas under active investigation in the use of PD-1/PD-L1 inhibitors for the treatment of HL.

  12. Immuno-oncologic Approaches: CAR-T Cells and Checkpoint Inhibitors.

    Science.gov (United States)

    Gay, Francesca; D'Agostino, Mattia; Giaccone, Luisa; Genuardi, Mariella; Festuccia, Moreno; Boccadoro, Mario; Bruno, Benedetto

    2017-08-01

    Advances in understanding myeloma biology have shown that disease progression is not only the consequence of intrinsic tumor changes but also of interactions between the tumor and the microenvironment in which the cancer grows. The immune system is an important component of the tumor microenvironment in myeloma, and acting on the immune system is an appealing new treatment strategy. There are 2 ways to act toward immune cells and boost antitumor immunity: (1) to increase antitumor activity (acting on T and NK cytotoxic cells), and (2) to reduce immunosuppression (acting on myeloid-derived stem cells and T regulatory cells). Checkpoint inhibitors and adoptive cell therapy (ACT) are 2 of the main actors, together with monoclonal antibodies and immunomodulatory agents, in the immune-oncologic approach. The aim of checkpoint inhibitors is to release the brakes that block the action of the immune system against the tumor. Anti-programmed death-1 (PD-1) and PD-1-Ligand, as well as anti-CTLA4 and KIR are currently under evaluation, as single agents or in combination, with the best results achieved so far with combination of anti-PD-1 and immunomodulatory agents. The aim of ACT is to create an immune effector specific against the tumor. Preliminary results on chimeric antigen receptor (CAR) T cells, first against CD19, and more recently against B-cell maturation antigen, have shown to induce durable responses in heavily pretreated patients. This review focuses on the most recent clinical results available on the use of checkpoint inhibitors and CAR-T cells in myeloma, in the context of the new immune-oncologic approach. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Requirement for PLK1 kinase activity in the maintenance of a robust spindle assembly checkpoint

    Directory of Open Access Journals (Sweden)

    Aisling O'Connor

    2016-01-01

    Full Text Available During mitotic arrest induced by microtubule targeting drugs, the weakening of the spindle assembly checkpoint (SAC allows cells to progress through the cell cycle without chromosome segregation occurring. PLK1 kinase plays a major role in mitosis and emerging evidence indicates that PLK1 is also involved in establishing the checkpoint and maintaining SAC signalling. However, mechanistically, the role of PLK1 in the SAC is not fully understood, with several recent reports indicating that it can cooperate with either one of the major checkpoint kinases, Aurora B or MPS1. In this study, we assess the role of PLK1 in SAC maintenance. We find that in nocodazole-arrested U2OS cells, PLK1 activity is continuously required for maintaining Aurora B protein localisation and activity at kinetochores. Consistent with published data we find that upon PLK1 inhibition, phosphoThr3-H3, a marker of Haspin activity, is reduced. Intriguingly, Aurora B inhibition causes PLK1 to relocalise from kinetochores into fewer and much larger foci, possibly due to incomplete recruitment of outer kinetochore proteins. Importantly, PLK1 inhibition, together with partial inhibition of Aurora B, allows efficient SAC override to occur. This phenotype is more pronounced than the phenotype observed by combining the same PLK1 inhibitors with partial MPS1 inhibition. We also find that PLK1 inhibition does not obviously cooperate with Haspin inhibition to promote SAC override. These results indicate that PLK1 is directly involved in maintaining efficient SAC signalling, possibly by cooperating in a positive feedback loop with Aurora B, and that partially redundant mechanisms exist which reinforce the SAC.

  14. Mutant p53 perturbs DNA replication checkpoint control through TopBP1 and Treslin.

    Science.gov (United States)

    Liu, Kang; Lin, Fang-Tsyr; Graves, Joshua D; Lee, Yu-Ju; Lin, Weei-Chin

    2017-05-09

    Accumulating evidence supports the gain-of-function of mutant forms of p53 (mutp53s). However, whether mutp53 directly perturbs the DNA replication checkpoint remains unclear. Previously, we have demonstrated that TopBP1 forms a complex with mutp53s and mediates their gain-of-function through NF-Y and p63/p73. Akt phosphorylates TopBP1 and induces its oligomerization, which inhibits its ATR-activating function. Here we show that various contact and conformational mutp53s bypass Akt to induce TopBP1 oligomerization and attenuate ATR checkpoint response during replication stress. The effect on ATR response caused by mutp53 can be exploited in a synthetic lethality strategy, as depletion of another ATR activator, DNA2, in mutp53-R273H-expressing cancer cells renders cells hypersensitive to cisplatin. Expression of mutp53-R273H also makes cancer cells more sensitive to DNA2 depletion or DNA2 inhibitors. In addition to ATR-activating function during replication stress, TopBP1 interacts with Treslin in a Cdk-dependent manner to initiate DNA replication during normal growth. We find that mutp53 also interferes with TopBP1 replication function. Several contact, but not conformational, mutp53s enhance the interaction between TopBP1 and Treslin and promote DNA replication despite the presence of a Cdk2 inhibitor. Together, these data uncover two distinct mechanisms by which mutp53 enhances DNA replication: ( i ) Both contact and conformational mutp53s can bind TopBP1 and attenuate the checkpoint response to replication stress, and ( ii ) during normal growth, contact (but not conformational) mutp53s can override the Cdk2 requirement to promote replication by facilitating the TopBP1/Treslin interaction.

  15. Effect of salt-inducible kinase 2 on checkpoint in response to γ-ray irradiation

    International Nuclear Information System (INIS)

    Yin Jiaojiao; Zhou Lijun; Wang Yu; Liu Xiaodan; Gu Yongqing; Zhou Pingkun

    2014-01-01

    Objective: To investigate the effect of salt-induced kinase 2 (SIK2) in the G_2/M checkpoint in response to ionizing radiation and the possible mechanism. Methods: HeLa cells were irradiated with "6"0Co γ-rays. The cell model of knockdown SIK2 expression was constrcuted by transfecting HeLa cells with a pSicoR-based lentivirus vector of expressing SIK2 shRNA by lipofectamin 2000. Western blot and flow cytometry were performed to measure the changes of SIK2 protein level and cell cycle distribution. The phosphorylated histone protein H3 on Ser 10 was used as a molecular marker of mitotic cells for detecting the function of G2/M checkpoint. Results: The expression level of SIK2 protein increased in HeLa cells after "6"0Co γ-ray irradiation. A cell model of knockdown SIK2 expression was successfully generated by transfecting the specific shRNA against SIK2. Depression of SIK2 significantly increased the cellular sensitivity at 1, 2, 4, 6 Gy post-irradiation (t = -3.445, -2.581, -3.251, -2.553, P < 0.05), and led cells to release earlier from the G_2/M boundary arrest compared to control cells at 5, 6 h post-irradiation(t = 4.341, 6.500, P < 0.05). Western blot analysis indicated that the irradiation-induced phosphorylated CHK2/T68 in SIK2 knock-down cells was earlier than that in control cells. Conclusions: salt-induced kinase 2 (SIK2) participates in the regulation of G_2/M checkpoint induced by ionizing radiation and affects cellular radiosensitivity. (authors)

  16. Cultural Clash and Educational Diversity: Immigrant Teachers' Efforts To Rescue the Education of Immigrant Children in Israel.

    Science.gov (United States)

    Epstein, Alek D.; Kheimets, Nina G.

    2000-01-01

    Presents the results of a study on the Mofet system (Israel), founded by immigrant teachers in 1991 as an effort to educate Russian immigrant children. Argues that although the success of the system is linked to the general education system's failure to meet immigrants' needs, it does not express Russian immigrant's desire for socio-cultural…

  17. Worse Cardiometabolic Health in African Immigrant Men than African American Men: Reconsideration of the Healthy Immigrant Effect

    OpenAIRE

    O'Connor, Michelle Y.; Thoreson, Caroline K.; Ricks, Madia; Courville, Amber B.; Thomas, Francine; Yao, Jianhua; Katzmarzyk, Peter T.; Sumner, Anne E.

    2014-01-01

    Background: The healthy immigrant effect is a phrase that has been used for decades to describe better cardiometabolic health in African immigrants than African Americans. The recent global increase in cardiometabolic diseases raises the possibility that immigrant health may be changing. Therefore, a new assessment of cardiometabolic health in African immigrants is warranted.

  18. Rad9 contribution to radiosensitivity and the G2 checkpoint in a DT40 cell line

    Energy Technology Data Exchange (ETDEWEB)

    Kumano, Tomoyasu [Kanazawa Univ. (Japan). Graduate School of Medical Science

    2002-12-01

    In fission yeast, the rad9 (radiation sensitive) gene was cloned from a mutant that is sensitive to ionizing radiation, ultraviolet and hydroxyurea. This gene has also been shown to be required for a DNA damage checkpoint. Orthologues of the rad9 gene have recently been identified in higher eukaryote cells including human. Here we generated Rad9 knockout (Rad9-/-) cells from the chicken B lymphocyte line DT40 to examine the role of Rad9 in higher eukaryotes. First we isolated a part of the chicken Rad9 gene which was 54% identical with human Rad9 at the amino acid sequence level. Next we isolated genomic clones, determined exons and introns, and constructed targeting vectors designed to disrupt exon 1-3 of the chicken Rad9 gene by replacement with a drug-resistant gene. Successful targeted integration was verified by Southern blot analysis and the disruption of the Rad9 gene was confirmed by reverse transcription polymerase chain reaction (RT-PCR). To analyze the radiosensitivity of these Rad9-/- cells, we monitored the clonogenic survival after various degrees of X-ray irradiation. Rad9-/- cells were more sensitive to X-rays than wild type cells at all dosages. However, these cells were less sensitive than ATM knockout (ATM-/-) cells that are known to be X-ray sensitive and that showed a defective checkpoint control. In contrast, Rad9-/- cells were markedly more sensitive to ultraviolet and hydroxyruea. In addition, we assessed the G2 checkpoint by measurement of the mitotic index that is the fraction of the accumulating number of cells in mitosis at various times after X-ray irradiation. While the number of mitotic wild type cells did not increase until 2 hrs after X-ray irradiation, the number of mitotic Rad9-/- cells showed an increase similar to that of ATM-/- cells. These results suggest that just as in fission yeast, in higher eukaryotes Rad9 also contributes to X-ray, ultraviolet and hydroxyurea sensitivity, and plays an important role in the G2 checkpoint

  19. Rad9 contribution to radiosensitivity and the G2 checkpoint in a DT40 cell line

    International Nuclear Information System (INIS)

    Kumano, Tomoyasu

    2002-01-01

    In fission yeast, the rad9 (radiation sensitive) gene was cloned from a mutant that is sensitive to ionizing radiation, ultraviolet and hydroxyurea. This gene has also been shown to be required for a DNA damage checkpoint. Orthologues of the rad9 gene have recently been identified in higher eukaryote cells including human. Here we generated Rad9 knockout (Rad9-/-) cells from the chicken B lymphocyte line DT40 to examine the role of Rad9 in higher eukaryotes. First we isolated a part of the chicken Rad9 gene which was 54% identical with human Rad9 at the amino acid sequence level. Next we isolated genomic clones, determined exons and introns, and constructed targeting vectors designed to disrupt exon 1-3 of the chicken Rad9 gene by replacement with a drug-resistant gene. Successful targeted integration was verified by Southern blot analysis and the disruption of the Rad9 gene was confirmed by reverse transcription polymerase chain reaction (RT-PCR). To analyze the radiosensitivity of these Rad9-/- cells, we monitored the clonogenic survival after various degrees of X-ray irradiation. Rad9-/- cells were more sensitive to X-rays than wild type cells at all dosages. However, these cells were less sensitive than ATM knockout (ATM-/-) cells that are known to be X-ray sensitive and that showed a defective checkpoint control. In contrast, Rad9-/- cells were markedly more sensitive to ultraviolet and hydroxyruea. In addition, we assessed the G2 checkpoint by measurement of the mitotic index that is the fraction of the accumulating number of cells in mitosis at various times after X-ray irradiation. While the number of mitotic wild type cells did not increase until 2 hrs after X-ray irradiation, the number of mitotic Rad9-/- cells showed an increase similar to that of ATM-/- cells. These results suggest that just as in fission yeast, in higher eukaryotes Rad9 also contributes to X-ray, ultraviolet and hydroxyurea sensitivity, and plays an important role in the G2 checkpoint

  20. Monitoring of scrap loads at Gorzia border checkpoints: A thirty months experience and some suggestions

    International Nuclear Information System (INIS)

    Fabretto, M.

    1999-01-01

    The following topics are highlighted: personnel training, assistance from foreign scrap suppliers, and computerized database. It is suggested that when selecting personnel for this job, major attention should be paid to their attitudes; the personnel should be given very good training, teaching them also how to make controls manually; expert physicist' support should be available within a very short time; each monitoring checkpoint should have its local electronic database; periodical exchange and updating of information should be practised on the standardization of methods of detection, of levels of attention and alarm, of statistics among the people in charge of EU and non-EU countries. (P.A.)

  1. Strategies to overcome HBV-specific T cell exhaustion: checkpoint inhibitors and metabolic re-programming.

    Science.gov (United States)

    Fisicaro, Paola; Boni, Carolina; Barili, Valeria; Laccabue, Diletta; Ferrari, Carlo

    2018-01-29

    HBV-specific T cells play a key role in antiviral protection and failure to control HBV is associated with severely dysfunctional T cell responses. Therefore, functional T cell reconstitution represents a potential way to treat chronically infected patients. The growing understanding of the dysregulated transcriptional/epigenetic and metabolic programs underlying T cell exhaustion allows to envisage functional T cell reconstitution strategies based on the combined/sequential use of compounds able to induce decline of antigen load, checkpoint modulation, metabolic and epigenetic reprogramming with possible boosting of functionally restored responses by specific vaccines. Copyright © 2018 Elsevier B.V. All rights reserved.

  2. Immigrant-Native Substitutability: The Role of Language Ability

    OpenAIRE

    Ethan G. Lewis

    2011-01-01

    Wage evidence suggests that immigrant workers are imperfectly substitutable for native-born workers with similar education and experience. Using U.S. Censuses and recent American Community Survey data, I ask to what extent differences in language skills drive this. I find they are important. I estimate that the response of immigrants' relative wages to immigration is concentrated among immigrants with poor English skills. Similarly, immigrants who arrive at young ages, as adults, both have st...

  3. Poverty and program participation among immigrant children.

    Science.gov (United States)

    Borjas, George J

    2011-01-01

    Researchers have long known that poverty in childhood is linked with a range of negative adult socioeconomic outcomes, from lower educational achievement and behavioral problems to lower earnings in the labor market. But few researchers have explored whether exposure to a disadvantaged background affects immigrant children and native children differently. George Borjas uses Current Population Survey (CPS) data on two specific indicators of poverty-the poverty rate and the rate of participation in public assistance programs-to begin answering that question. He finds that immigrant children have significantly higher rates both of poverty and of program participation than do native children. Nearly half of immigrant children are being raised in households that receive some type of public assistance, compared with roughly one-third of native children. Although the shares of immigrant and native children living in poverty are lower, the rate for immigrant children is nonetheless about 15 percentage points higher than that for native children-about the same as the gap in public assistance. Poverty and program participation rates among different groups of immigrant children also vary widely, depending in part on place of birth (foreign- or U.S.-born), parents (immigrant or native), and national origin. According to the CPS data, these native-immigrant differences persist into young adulthood. In particular, the program participation and poverty status of immigrant children is strongly correlated with their program participation and poverty status when they become young adults. But it is not possible, says Borjas, to tell whether the link results from a set of permanent factors associated with specific individuals or groups that tends to lead to "good" or "bad" outcomes systematically over time or from exposure during childhood to adverse socioeconomic outcomes, such as poverty or welfare dependency. Future research must explore the causal impact of childhood poverty on

  4. Determinants of Recent Immigrants' Location Choices

    DEFF Research Database (Denmark)

    Damm, Anna Piil

    2009-01-01

    This paper exploits a Danish spatial dispersal policy on refugees which can be regarded as a natural experiment to investigate the influence of regional factors on recent immigrants' location choices. The main push factors are lack of co-nationals and immigrants. Additional push factors are lack...... of rental, including social, housing and lack of institutions for qualifying educations which explain why recent immigrants are attracted to large cities. Finally, placed refugees tend to leave locations with relatively high regional unemployment and there is indirect evidence of welfare seeking....

  5. Illegal aliens, unemployment and immigration policy.

    Science.gov (United States)

    Djajic, S

    1987-02-01

    "This paper develops a simple two-country model of illegal immigration in an attempt to examine the interaction among variables such as the stock of migrant labor, the unemployment rates of the two economies, and the rate of spending by the host country on the enforcement of its immigration restrictions. The focus of the analysis is on the dynamics of immigration policy and on its role in determining the nature of the mechanism by which disturbances to the labor market of one country are transmitted to that of the other in the short run and in the long run." excerpt

  6. In vitro analysis of the role of replication protein A (RPA) and RPA phosphorylation in ATR-mediated checkpoint signaling.

    Science.gov (United States)

    Lindsey-Boltz, Laura A; Reardon, Joyce T; Wold, Marc S; Sancar, Aziz

    2012-10-19

    Replication protein A (RPA) plays essential roles in DNA metabolism, including replication, checkpoint, and repair. Recently, we described an in vitro system in which the phosphorylation of human Chk1 kinase by ATR (ataxia telangiectasia mutated and Rad3-related) is dependent on RPA bound to single-stranded DNA. Here, we report that phosphorylation of other ATR targets, p53 and Rad17, has the same requirements and that RPA is also phosphorylated in this system. At high p53 or Rad17 concentrations, RPA phosphorylation is inhibited and, in this system, RPA with phosphomimetic mutations cannot support ATR kinase function, whereas a non-phosphorylatable RPA mutant exhibits full activity. Phosphorylation of these ATR substrates depends on the recruitment of ATR and the substrates by RPA to the RPA-ssDNA complex. Finally, mutant RPAs lacking checkpoint function exhibit essentially normal activity in nucleotide excision repair, revealing RPA separation of function for checkpoint and excision repair.

  7. In Vitro Analysis of the Role of Replication Protein A (RPA) and RPA Phosphorylation in ATR-mediated Checkpoint Signaling*

    Science.gov (United States)

    Lindsey-Boltz, Laura A.; Reardon, Joyce T.; Wold, Marc S.; Sancar, Aziz

    2012-01-01

    Replication protein A (RPA) plays essential roles in DNA metabolism, including replication, checkpoint, and repair. Recently, we described an in vitro system in which the phosphorylation of human Chk1 kinase by ATR (ataxia telangiectasia mutated and Rad3-related) is dependent on RPA bound to single-stranded DNA. Here, we report that phosphorylation of other ATR targets, p53 and Rad17, has the same requirements and that RPA is also phosphorylated in this system. At high p53 or Rad17 concentrations, RPA phosphorylation is inhibited and, in this system, RPA with phosphomimetic mutations cannot support ATR kinase function, whereas a non-phosphorylatable RPA mutant exhibits full activity. Phosphorylation of these ATR substrates depends on the recruitment of ATR and the substrates by RPA to the RPA-ssDNA complex. Finally, mutant RPAs lacking checkpoint function exhibit essentially normal activity in nucleotide excision repair, revealing RPA separation of function for checkpoint and excision repair. PMID:22948311

  8. Targeting Tumor-Associated Macrophages as a Potential Strategy to Enhance the Response to Immune Checkpoint Inhibitors.

    Science.gov (United States)

    Cassetta, Luca; Kitamura, Takanori

    2018-01-01

    Inhibition of immune checkpoint pathways in CD8 + T cell is a promising therapeutic strategy for the treatment of solid tumors that has shown significant anti-tumor effects and is now approved by the FDA to treat patients with melanoma and lung cancer. However the response to this therapy is limited to a certain fraction of patients and tumor types, for reasons still unknown. To ensure success of this treatment, CD8 + T cells, the main target of the checkpoint inhibitors, should exert full cytotoxicity against tumor cells. However recent studies show that tumor-associated macrophages (TAM) can impede this process by different mechanisms. In this mini-review we will summarize recent studies showing the effect of TAM targeting on immune checkpoint inhibitors efficacy. We will also discuss on the limitations of the current strategies as well on the future scientific challenges for the progress of the tumor immunology field.

  9. The Healthy Immigrant Effect and Immigrant Selection: Evidence from Four Countries

    OpenAIRE

    Steven Kennedy; James Ted McDonald; Nicholas Biddle

    2006-01-01

    The existence of a healthy immigrant effect – where immigrants are on average healthier than the native-born – is now a well accepted phenomenon. There are many competing explanations for this phenomenon including health screening by recipient countries, healthy behaviour prior to migration followed by the steady adoption of new country (less) healthy behaviours, and immigrant self-selection where healthier and wealthier people tend to be migrants. We explore the last two of these explanation...

  10. Grp/DChk1 is required for G(2)-M checkpoint activation in Drosophila S2 cells, whereas Dmnk/DChk2 is dispensable

    NARCIS (Netherlands)

    de Vries, HI; Uyetake, L; Lemstra, W; Brunsting, JF; Su, TT; Kampinga, HH; Sibon, OCM

    2005-01-01

    Cell-cycle checkpoints are signal-transduction pathways required to maintain genomic stability in dividing cells. Previously, it was reported that two kinases essential for checkpoint signalling, Chk1 and Chk2 are structurally conserved. In contrast to yeast, Xenopus and mammals, the Chk1- and

  11. The Geography of Deterrence: Exploring the Small Area Effects of Sobriety Checkpoints on Alcohol-Impaired Collision Rates within a City

    Science.gov (United States)

    Nunn, Samuel; Newby, William

    2011-01-01

    This article examines alcohol-impaired collision metrics around nine sobriety checkpoint locations in Indianapolis, Indiana, before and after implementation of 22 checkpoints, using a pre/post examination, a pre/post nonequivalent comparison group analysis, and an interrupted time series approach. Traffic safety officials used geographical…

  12. Nek2A destruction marks APC/C activation at the prophase-to-prometaphase transition by spindle-checkpoint-restricted Cdc20.

    Science.gov (United States)

    Boekhout, Michiel; Wolthuis, Rob

    2015-04-15

    Nek2 isoform A (Nek2A) is a presumed substrate of the anaphase-promoting complex/cyclosome containing Cdc20 (APC/C(Cdc20)). Nek2A, like cyclin A, is degraded in mitosis while the spindle checkpoint is active. Cyclin A prevents spindle checkpoint proteins from binding to Cdc20 and is recruited to the APC/C in prometaphase. We found that Nek2A and cyclin A avoid being stabilized by the spindle checkpoint in different ways. First, enhancing mitotic checkpoint complex (MCC) formation by nocodazole treatment inhibited the degradation of geminin and cyclin A, whereas Nek2A disappeared at a normal rate. Second, depleting Cdc20 effectively stabilized cyclin A but not Nek2A. Nevertheless, Nek2A destruction crucially depended on Cdc20 binding to the APC/C. Third, in contrast to cyclin A, Nek2A was recruited to the APC/C before the start of mitosis. Interestingly, the spindle checkpoint very effectively stabilized an APC/C-binding mutant of Nek2A, which required the Nek2A KEN box. Apparently, in cells, the spindle checkpoint primarily prevents Cdc20 from binding destruction motifs. Nek2A disappearance marks the prophase-to-prometaphase transition, when Cdc20, regardless of the spindle checkpoint, activates the APC/C. However, Mad2 depletion accelerated Nek2A destruction, showing that spindle checkpoint release further increases APC/C(Cdc20) catalytic activity. © 2015. Published by The Company of Biologists Ltd.

  13. Structural basis of a novel PD-L1 nanobody for immune checkpoint blockade.

    Science.gov (United States)

    Zhang, Fei; Wei, Hudie; Wang, Xiaoxiao; Bai, Yu; Wang, Pilin; Wu, Jiawei; Jiang, Xiaoyong; Wang, Yugang; Cai, Haiyan; Xu, Ting; Zhou, Aiwu

    2017-01-01

    The use of antibodies to target immune checkpoints, particularly PD-1/PD-L1, has made a profound impact in the field of cancer immunotherapy. Here, we identified KN035, an anti-PD-L1 nanobody that can strongly induce T-cell responses and inhibit tumor growth. The crystal structures of KN035 complexed with PD-L1 and free PD-L1, solved here at 1.7 and 2.7 Å resolution, respectively, show that KN035 competes with PD-1 (programmed death protein 1) for the same flat surface on PD-L1, mainly through a single surface loop of 21 amino acids. This loop forms two short helices and develops key hydrophobic and ionic interactions with PD-L1 residues, such as Ile54, Tyr56 and Arg113, which are also involved in PD-1 binding. The detailed mutagenesis study identified the hotspot residues of the PD-L1 surface and provides an explanation for the stronger (~1 000-fold) binding of KN035 to PD-L1 than PD-1 and its lack of binding to PD-L2. Overall, this study reveals how a single immunoglobulin-variable scaffold of KN035 or PD-1 can bind to a flat protein surface through either a single surface loop or beta-sheet strands; and provides a basis for designing new immune checkpoint blockers and generating bi-specific antibodies for combination therapy.

  14. Nucleotide Selectivity at a Preinsertion Checkpoint of T7 RNA Polymerase Transcription Elongation.

    Science.gov (United States)

    E, Chao; Duan, Baogen; Yu, Jin

    2017-04-20

    Nucleotide selection is crucial for transcription fidelity control, in particular, for viral T7 RNA polymerase (RNAP) lack of proofreading activity. It has been recognized that multiple kinetic checkpoints exist prior to full nucleotide incorporation. In this work, we implemented intensive atomistic molecular dynamics (MD) simulations to quantify how strong the nucleotide selection is at the initial checkpoint of an elongation cycle of T7 RNAP. The incoming nucleotides bind into a preinsertion site where a critical tyrosine residue locates nearby to assist the nucleotide selection. We calculated the relative binding free energy between a noncognate nucleotide and a cognate one at a preinsertion configuration via alchemical simulations, showing that a small selection free energy or the binding free energy difference (∼3 k B T) exists between the two nucleotides. Indeed, another preinsertion configuration favored by the noncognate nucleotides was identified, which appears to be off path for further nucleotide insertion and additionally assists the nucleotide selection. By chemical master equation (CME) approach, we show that the small selection free energy at the preinsertion site along with the off-path noncognate nucleotide filtering can help substantially to reduce the error rate and to maintain the elongation rate high in the T7 RNAP transcription.

  15. Checkpoint-dependent RNR induction promotes fork restart after replicative stress.

    Science.gov (United States)

    Morafraile, Esther C; Diffley, John F X; Tercero, José Antonio; Segurado, Mónica

    2015-01-20

    The checkpoint kinase Rad53 is crucial to regulate DNA replication in the presence of replicative stress. Under conditions that interfere with the progression of replication forks, Rad53 prevents Exo1-dependent fork degradation. However, although EXO1 deletion avoids fork degradation in rad53 mutants, it does not suppress their sensitivity to the ribonucleotide reductase (RNR) inhibitor hydroxyurea (HU). In this case, the inability to restart stalled forks is likely to account for the lethality of rad53 mutant cells after replication blocks. Here we show that Rad53 regulates replication restart through the checkpoint-dependent transcriptional response, and more specifically, through RNR induction. Thus, in addition to preventing fork degradation, Rad53 prevents cell death in the presence of HU by regulating RNR-expression and localization. When RNR is induced in the absence of Exo1 and RNR negative regulators, cell viability of rad53 mutants treated with HU is increased and the ability of replication forks to restart after replicative stress is restored.

  16. Immune checkpoint inhibitors for non-small-cell lung cancer: does that represent a 'new frontier'?

    Science.gov (United States)

    Pilotto, Sara; Kinspergher, Stefania; Peretti, Umberto; Calio, Anna; Carbognin, Luisa; Ferrara, Roberto; Brunelli, Matteo; Chilosi, Marco; Tortora, Giampaolo; Bria, Emilio

    2015-01-01

    Advances in the interpretation and understanding of cancer behaviour, particularly of its ability to evade the host immunosurveillance, deregulating the balance between inhibitory and stimulatory factors, led to the development of an innovative category of immunotherapeutic agents, currently under investigation. Although the disappointing data deriving from the employment of vaccines in non-small cell lung cancer (NSCLC), more promising results have been obtained in the early phase trials with immune checkpoint inhibitors, such as cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), programmed cell death protein-1 (PD-1) and programmed death-ligand 1 (PD-L1) inhibitors. This review delineates the main features of the available immunotherapeutic agents, focusing the discussion on immune checkpoint inhibitors, those that have already demonstrated a relevant clinical activity (such as Ipilimumab and Nivolumab) and those molecules still in early development phase. Moreover, we underline the possible emerging issues deriving from the progressive diffusion of Immuno-Oncology into the standard clinical practice. The careful and accurate identification and management of immune-related toxicities, the validation of more reliable immune response criteria and the increasing research of potential predictive biomarkers are key points of discussion. The perspective is that immunotherapy might represent an effective 'magic bullet', able to change the treatment paradigm of NSCLC, particularly of those subgroups featured by a heavily mutant cancer (squamous histology and smokers), where the immunologic agents contribute in cancer development and progression seems to be strong and, concurrently, the efficacy of standard therapies particularly limited.

  17. Preferential radiosensitization of G1 checkpoint--deficient cells by methylxanthines

    International Nuclear Information System (INIS)

    Russell, Kenneth J.; Wiens, Linda W.; Demers, G. William; Galloway, Denise A.; Le, Tiep; Rice, Glenn C.; Bianco, James A.; Singer, Jack W.; Groudine, Mark

    1996-01-01

    Purpose: To develop a checkpoint-based strategy for preferential radiosensitization of human tumors with deficient and/or mutant p53. Methods and Materials: A549 human lung adenocarcinoma cell lines differing in their expression of the p53 tumor suppressor gene were produced by transduction with the E6 oncogene from human papilloma virus type 16. The cells expressing E6 (E6+) lack a G1 arrest in response to ionizing radiation, are deficient in p53 and p21 expression, and exhibit a fivefold greater clonogenic survival following 10 Gy radiation. Results: Postirradiation incubation with millimolar concentrations of the methylxanthine pentoxifylline (PTX) results in preferential radiosensitization of the E6+ cells compared to the LXSN+ vector transduced controls. There is a threefold sensitization of the LXSN+ cells and a 15-fold sensitization of the E6+ cells, which results in equal clonogenic survival of the two lines. Flow cytometry reveals PTX abrogation of the radiation induced G2 arrest for both cell lines. PTX also prolongs G1 transit for both cell lines. Preliminary results are presented using a novel methylxanthine, lisofylline (LSF), which has similar cell cycle effects on G1 and G2 and achieves differential radiosensitization at micromolar concentrations that are sustainable in humans. Conclusions: This checkpoint-based strategy is a promising approach for achieving preferential radiosensitization of p53- tumors relative to p53+ normal tissues

  18. Hepatic neuregulin 4 signaling defines an endocrine checkpoint for steatosis-to-NASH progression

    Science.gov (United States)

    Guo, Liang; Chen, Zhimin; Xia, Houjun; Li, Siming; Zhang, Yanqiao; Kobberup, Sune; Zou, Weiping; Lin, Jiandie D.

    2017-01-01

    Nonalcoholic steatohepatitis (NASH) is characterized by progressive liver injury, inflammation, and fibrosis; however, the mechanisms that govern the transition from hepatic steatosis, which is relatively benign, to NASH remain poorly defined. Neuregulin 4 (Nrg4) is an adipose tissue–enriched endocrine factor that elicits beneficial metabolic effects in obesity. Here, we show that Nrg4 is a key component of an endocrine checkpoint that preserves hepatocyte health and counters diet-induced NASH in mice. Nrg4 deficiency accelerated liver injury, fibrosis, inflammation, and cell death in a mouse model of NASH. In contrast, transgenic expression of Nrg4 in adipose tissue alleviated diet-induced NASH. Nrg4 attenuated hepatocyte death in a cell-autonomous manner by blocking ubiquitination and proteasomal degradation of c-FLIPL, a negative regulator of cell death. Adeno-associated virus–mediated (AAV-mediated) rescue of hepatic c-FLIPL expression in Nrg4-deficent mice functionally restored the brake for steatosis to NASH transition. Thus, hepatic Nrg4 signaling serves as an endocrine checkpoint for steatosis-to-NASH progression by activating a cytoprotective pathway to counter stress-induced liver injury. PMID:29106384

  19. Molecular basis of APC/C regulation by the spindle assembly checkpoint

    Science.gov (United States)

    Zhang, Ziguo; Yang, Jing; Maslen, Sarah; Skehel, Mark; Barford, David

    2016-01-01

    In the dividing eukaryotic cell the spindle assembly checkpoint (SAC) ensures each daughter cell inherits an identical set of chromosomes. The SAC coordinates the correct attachment of sister chromatid kinetochores to the mitotic spindle with activation of the anaphase-promoting complex/cyclosome (APC/C), the E3 ubiquitin ligase that initiates chromosome separation. In response to unattached kinetochores, the SAC generates the mitotic checkpoint complex (MCC), a multimeric assembly that inhibits the APC/C, delaying chromosome segregation. Here, using cryo-electron microscopy we determined the near-atomic resolution structure of an APC/C-MCC complex (APC/CMCC). We reveal how degron-like sequences of the MCC subunit BubR1 block degron recognition sites on Cdc20, the APC/C coactivator subunit (Cdc20APC/C) responsible for substrate interactions. BubR1 also obstructs binding of UbcH10 (APC/C’s initiating E2) to repress APC/C ubiquitination activity. Conformational variability of the complex allows for UbcH10 association, and we show from a structure of APC/CMCC in complex with UbcH10 how the Cdc20 subunit intrinsic to the MCC (Cdc20MCC) is ubiquitinated, a process that results in APC/C reactivation when the SAC is silenced. PMID:27509861

  20. The impact of aviation checkpoint queues on optimizing security screening effectiveness

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Adrian J., E-mail: ajlee@citeri.or [Central Illinois Technology and Education Research Institute, 2312 Connie Drive, Springfield, IL 62704-8722 (United States); Jacobson, Sheldon H., E-mail: shj@illinois.ed [Department of Computer Science, University of Illinois at Urbana-Champaign, 201 N. Goodwin Ave. M/C 258, Urbana, IL 61801-2302 (United States)

    2011-08-15

    Passenger screening at aviation security checkpoints is a critical component in protecting airports and aircraft from terrorist threats. Recent developments in screening device technology have increased the ability to detect these threats; however, the average amount of time it takes to screen a passenger still remains a concern. This paper models the queueing process for a multi-level airport checkpoint security system, where multiple security classes are formed through subsets of specialized screening devices. An optimal static assignment policy is obtained which minimizes the steady-state expected amount of time a passenger spends in the security system. Then, an optimal dynamic assignment policy is obtained through a transient analysis that balances the expected number of true alarms with the expected amount of time a passenger spends in the security system. Performance of a two-class system is compared to that of a selective security system containing primary and secondary levels of screening. The key contribution is that the resulting optimal assignment policies increase security and passenger throughput by efficiently and effectively utilizing available screening resources.

  1. The impact of aviation checkpoint queues on optimizing security screening effectiveness

    International Nuclear Information System (INIS)

    Lee, Adrian J.; Jacobson, Sheldon H.

    2011-01-01

    Passenger screening at aviation security checkpoints is a critical component in protecting airports and aircraft from terrorist threats. Recent developments in screening device technology have increased the ability to detect these threats; however, the average amount of time it takes to screen a passenger still remains a concern. This paper models the queueing process for a multi-level airport checkpoint security system, where multiple security classes are formed through subsets of specialized screening devices. An optimal static assignment policy is obtained which minimizes the steady-state expected amount of time a passenger spends in the security system. Then, an optimal dynamic assignment policy is obtained through a transient analysis that balances the expected number of true alarms with the expected amount of time a passenger spends in the security system. Performance of a two-class system is compared to that of a selective security system containing primary and secondary levels of screening. The key contribution is that the resulting optimal assignment policies increase security and passenger throughput by efficiently and effectively utilizing available screening resources.

  2. Health disparities between immigrant and Danish cleaners

    DEFF Research Database (Denmark)

    Jørgensen, Marie B; Rasmussen, Charlotte D N; Carneiro, Isabella G

    2011-01-01

    hundred and fifty-one cleaners, consisting of 166 Danes (88% women) and 179 immigrants (74% women) (6 with unknown ethnicity), from 9 workplaces in Denmark participated in the study. Health and work ability were obtained by objective (e.g., BMI and blood pressure) and self-reported measures (e.g., work......PURPOSE: It is unknown whether immigrants working in the cleaning industry have a poorer health and work ability than cleaners from the native population. The main aim was to investigate differences in objective and self-reported health measures between immigrant and Danish cleaners. METHODS: Three...... ability, self-rated health, and musculoskeletal symptoms). In order to investigate differences between Danish and immigrant cleaners, logistic regression analyses and General Linear Models were performed. RESULTS: When controlling for age, sex, workplace, job seniority, and smoking, more Danish compared...

  3. David Miller on Immigration Policy and Nationality

    DEFF Research Database (Denmark)

    Lægaard, Sune

    2007-01-01

    David Miller's recent statement of the case for restrictive immigration policies can plausibly be construed as an application of a ‘liberal nationalist' position. The paper first addresses Miller's critique of distributive justice arguments for open borders, which relies on nationality as determi......David Miller's recent statement of the case for restrictive immigration policies can plausibly be construed as an application of a ‘liberal nationalist' position. The paper first addresses Miller's critique of distributive justice arguments for open borders, which relies on nationality...... as determinative of the scope of distributive justice and as giving rise to national collective responsibility. Three interpretations of his main positive reason for restricting immigration, which concerns the importance of a shared public culture, are then discussed: culture as having valuable social functions...... in relation to immigration policy....

  4. FY 2013 ICE Immigration Removal Statistics

    Data.gov (United States)

    Department of Homeland Security — In addition to its criminal investigative responsibilities, U.S. Immigration and Customs Enforcement (ICE) shares responsibility for enforcing the nation’s civil...

  5. [Haiti, new immigrant community in Chile].

    Science.gov (United States)

    Sánchez P, Katherin; Valderas J, Jaime; Messenger C, Karen; Sánchez G, Carolina; Barrera Q, Francisco

    2018-04-01

    Migration is a growing phenomenon in Latin America influenced by several factors such as economic stability, employment, social welfare, education and health system. Currently Chile has a positive migration flow rate. Particularly, a significant number of Haitian immigrants has been observed du ring the last years, especially after earthquake of 2010. These immigrants present a different cultural background expressed in relevant aspects of living including parenting and healthcare. Knowing the Haitian culture and its health situation is relevant for a better understanding of their health needs. Haitian people come to Chile looking for a cordial reception and willing to find a place with better perspectives of wellbeing in every sense. Immigration represents a major challenge for Chilean health system that must be embraced. Integration efforts in jobs, health, education system and community living should be enhanced to ensure a prosper settlement in our country. A new immigration law is crucial to solving major problems derived from current law created in 1975.

  6. [Mental disorders among immigrants in Chile].

    Science.gov (United States)

    Rojas, Graciela; Fritsch, Rosemarie; Castro, Ariel; Guajardo, Viviana; Torres, Pamela; Díaz, Berta

    2011-10-01

    Chile is receiving immigrant populations coming from other Latin-American countries. To determine the prevalence of Common Mental Disorders (CMD) among immigrants who live in Independencia, a quarter in Santiago, Chile. A cross sectional study was carried out in the primary health care clinic and in the state-funded school of Independencia. A representative sample of 282 adults and 341 children were interviewed. Mental disorders were diagnosed using CIS-R and MINI structured interviews. The interviewed immigrants came mostly from Peru. The prevalence of mental disorders in the adult population was 17.8% and among children, it was 29.3%. The adult immigrants have a lower prevalence of mental disorders than the Chilean population but it increases among children. Barriers of access to health services, that should be solved, were detected.

  7. Immigrants, Labour Market Performance, and Social Insurance

    OpenAIRE

    Bratsberg, Bernt; Raaum, Oddbjørn; Røed, Knut

    2014-01-01

    Using longitudinal data from the date of arrival, we study long-term labour market and social insurance outcomes for all major immigrant cohorts to Norway since 1970. Immigrants from high-income countries performed as natives, while labour migrants from low-income source countries had declining employment rates and increasing disability programme participation over the lifecycle. Refugees and family migrants assimilated during the initial period upon arrival but labour market convergence halt...

  8. Internal migration and income of immigrant families

    OpenAIRE

    Rashid, Saman

    2004-01-01

    Using a longitudinal dataset from the years 1995 and 2000, respectively, this study examines whether migration within the host country of Sweden generates higher total annual income for (two-earner) immigrant families. The empirical findings indicate that internal migration generates a positive outcome in terms of higher family income for newly arrived refugee-immigrant families. Further, with the length of residence in the host country, the monetary gain accruing from internal migration decr...

  9. Immigrants, Labor Market Performance, and Social Insurance

    OpenAIRE

    Bratsberg, Bernt; Raaum, Oddbjørn; Røed, Knut

    2014-01-01

    Using longitudinal data from the date of arrival, we study long- term labor market and social insurance outcomes for all major immigrant cohorts to Norway since 1970. Immigrants from highincome countries performed as natives, while labor migrants from low- income source countries had declining employment rates and increasing disability program participation over the lifecycle. Refugees and family migrants assimilated during the initial period upon arrival, but labor market convergence halted ...

  10. The Societal Integration of Immigrants in Germany

    OpenAIRE

    Fertig, Michael

    2004-01-01

    This paper investigates whether and to what extent immigrants in Germany are integrated into German society by utilizing a variety of qualitative information and subjective data collected in the 1999 wave of the German Socio-Economic Panel (GSOEP). To this end, leisure-time activities and attitudes of native Germans, ethnic Germans and foreign immigrants of different generations are compared. The empirical results suggest that conditional on observable characteristics the activities and attit...

  11. State Dependence in Unemployment among Danish Immigrants

    DEFF Research Database (Denmark)

    Ahmad, Nisar

    2009-01-01

    This study examines the extent state dependence among unemployed Danish immigrants in a dynamic discrete choice framework. Three alternative methodologies are employed to control for the problem of the initial condition. The empirical findings show that there is a considerable correlation between...... compared to an individual who was employed at period “t-1”. This average partial effect is the same for western compared to non-western immigrants and women compared to men....

  12. Transnational dental care among Canadian immigrants.

    Science.gov (United States)

    Calvasina, Paola; Muntaner, Carles; Quiñonez, Carlos

    2015-10-01

    This study examines predictors of transnational dental care utilization, or the use of dental care across national borders, over a 4-year period among immigrants to Canada. Data from the Longitudinal Survey of Immigrants to Canada (LSIC, 2001-2005) were used. Sampling and bootstrap weights were applied to make the data nationally representative. Bivariate and multiple logistic regression analyses were applied to identify factors associated with immigrants' transnational dental care utilization. Approximately 13% of immigrants received dental care outside Canada over a period of 4 years. Immigrants lacking dental insurance (OR = 2.05; 95% CI: 1.55-2.70), those reporting dental problems (OR = 1.45; 95% CI: 1.12-1.88), who were female (OR = 1.59; 95% CI: 1.22-2.08), aged ≥ 50 years (OR = 2.30; 95% CI: 1.45-3.64), and who were always unemployed (OR = 1.70; 95% CI: 1.20-2.39) were more likely to report transnational dental care utilization. History of social assistance was inversely correlated with the use of dental services outside Canada (OR = 0.48; 95% CI: 0.30-0.83). It is estimated that roughly 11 500 immigrants have used dental care outside Canada over a 4-year period. Although transnational dental care utilization may serve as an individual solution for immigrants' initial barriers to accessing dental care, it demonstrates weaknesses to in-country efforts at providing publicly funded dental care to socially marginalized groups. Policy reforms should be enacted to expand dental care coverage among adult immigrants. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. Trends in labour immigration to the Netherlands

    OpenAIRE

    Alberda, A.P.; Bloemendal, C.; Braams, N.; Fortanier, F.; van Gaalen, R.; Rooijakkers, B.; Smit, R.

    2011-01-01

    The process of internationalisation is not only reflected in increased international trade and investment flows, but also in the increased movement of people across borders, often to take on jobs abroad (labour migration). Between 2000 and 2008, labour immigration to the Netherlands displayed a v-shaped trend, decreasing to a low of 32 thousand in 2004, and rising to 59 thousand in 2008. This trend mirrors the development of Dutch unemployment rates in this period. Many labour immigrants are ...

  14. The politicisation of UK immigration policy

    OpenAIRE

    Onslow-Cole, Julia

    2005-01-01

    Article by Julia Onslow-Cole (A senior partner and head of CMS Cameron McKenna's global immigration business practice) examining the development of UK business immigration law from 2003-4. Published in Amicus Curiae - Journal of the Society for Advanced Legal Studies. The Journal is produced by the Society for Advanced Legal Studies at the Institute of Advanced Legal Studies, University of London.

  15. Intermarriage among New Immigrants in the USA.

    Science.gov (United States)

    Bohra-Mishra, Pratikshya; Massey, Douglas S

    The study uses the New Immigrant Survey data collected in 2003 to fill a void in the existing literature on the regional variations in exogamy among the new first generation immigrants in the United States. It further improves on some methodological issues in existing studies. Our empirical results show that immigrants from different regions of origin indeed vary significantly in their choice of spouse, even after controlling for other important predictors of exogamy. Latino females are the most exogamous of all groups while Latino males as well are more exogamous than their Asian male counterparts and do not differ much from male immigrants from Europe, Central Asia and the residual "other" category. The results are somewhat counterintuitive given the history of European immigration to the US, and the higher level of structural assimilation attained by Asians in the US compared to Latinos. The contradictory results therefore, point towards a rapid assimilation of Latin Americans into the US society. On the other hand, first generation Asians demonstrated the lowest level of all types of exogamy in general, except Asian women were not the most endogamous compared to Europeans, Central Asians and "other" residual category. The finding, once again is inconsistent with the history of European immigration. Finally, although Latinos are more exogamous, they preferred a Hispanic spouse than a non-Hispanic, which could be attributed to the common Spanish language shared by them. In contrast, lack of a common language among Asians might be contributing to their lowest intermarriage rate with other Asians, irrespective of gender.

  16. Fertility behaviour of recent immigrants to Israel

    Directory of Open Access Journals (Sweden)

    2004-03-01

    Full Text Available The fertility practices of immigrants are a particularly interesting field of study for demographers, providing an insight into the fertility behaviour of individuals when both the society and the individual undergo a period of rapid change. This paper describes and compares the fertility behaviour of two large groups of immigrants, from the former Soviet Union (FSU and from Ethiopia to Israel in the last 20 years. The changes in fertility behaviour undergone in the same society and at the same time by two very different groups are examined. The findings reveal that the fertility behaviour of immigrants is indeed changing. The fertility of FSU immigrants is increasing and that of the Ethiopian immigrants decreasing, with accompanying changes in the proximate determinants of fertility. Although the fertility of immigrants is becoming more similar to that of the receiving society, the methods employed to achieve the fertility change are not necessarily similar, and, in some cases, diverge from the norms of the receiving society.

  17. Acculturation, adaptation and multiculturalism among immigrant adolescents in junior vocational education

    NARCIS (Netherlands)

    Geel, Mitch van

    2009-01-01

    This thesis deals with the adaptation and acculturation of immigrant adolescents in junior vocational education. The adaptation of immigrant adolescents fits the notion of an 'immigrant paradox'. Maintaining aspects of the ethnic culture was found positively related to immigrant adolescents'

  18. Immigration Ethnic Diversity and Political Outcomes: Evidence from Denmark

    DEFF Research Database (Denmark)

    Harmon, Nikolaj Arpe

    I study the impact of immigration and increasing ethnic diversity on political outcomes in immigrant-receiving countries, focusing on immigration and election outcomes in Danish municipalities 1981-2001. A rich set of control variables isolates ethnic diversity effects from those of other immigrant...... characteristics and a novel IV strategy based on historical housing stock data addresses issues of endogenous location choices of immigrants. Increases in local ethnic diversity lead to right-ward shifts in election outcomes by shifting electoral support away from traditional "big government" left-wing parties...... and towards anti-immigrant nationalist parties in particular. These effects appear in both local and national elections....

  19. Storytelling in Critical Literacy Pedagogy: Removing the Walls between Immigrant and Non-Immigrant Youth

    Science.gov (United States)

    Enciso, Patricia

    2011-01-01

    The central focus of this research has been to document immigrant and non-immigrant students' storytelling practices and cultural knowledge and identify how these might be adapted as "cultural data sets" for academic literary study in ethnically and linguistically heterogeneous, middle-grade classrooms. Such data sets, however, have limited use…

  20. The impact of immigration on the breastfeeding practices of Mainland Chinese immigrants in Hong Kong.

    Science.gov (United States)

    Lok, Kris Yuet Wan; Bai, Dorothy Li; Chan, Noel P T; Wong, Janet Y H; Tarrant, Marie

    2018-03-01

    Researchers have found breastfeeding disparities between immigrant and native-born women in many countries. However, most studies on immigration and breastfeeding practices have been in Western countries. The aim of this study was to examine the effect of length of time since immigration on the breastfeeding practices of Mainland Chinese immigrants living in Hong Kong. We recruited 2704 mother-infant pairs from the postnatal wards of four public hospitals in Hong Kong. We examined the effect of migration status on the duration of any and exclusive breastfeeding. Breastfeeding duration was progressively shorter as the time since immigration increased. When compared with mothers who had lived in Hong Kong for Hong Kong-born participants had a 30% higher risk of stopping any breastfeeding (hazard ratio [HR] 1.34 [95% confidence interval {CI} 1.10-1.63]) and exclusive breastfeeding (HR 1.33 [95% CI 1.11-1.58]). In both Hong Kong-born and immigrant participants, breastfeeding cessation was associated with return to work postpartum and the husband's preference for infant formula or mixed feeding. Intention to exclusively breastfeed and to breastfeed for >6 months, and previous breastfeeding experience substantially reduced the risk of breastfeeding cessation for both Hong Kong-born and immigrant participants. Health care professionals should consider immigration history in their assessment of pregnant women and provide culturally adapted breastfeeding support and encouragement to this population. © 2017 Wiley Periodicals, Inc.

  1. Troubling the Proletarianization of Mexican Immigrant Students in an Era of Neoliberal Immigration

    Science.gov (United States)

    Choudry, Aziz

    2010-01-01

    In response to Richardson Bruna's "Mexican immigrant transnational social capital and class transformation: examining the role of peer mediation in insurgent science", this paper draws on the author's research on organizing, mobilization and knowledge production among adult im/migrant workers in Canada. While appreciative of the content…

  2. Inflammatory bowel disease is presenting sooner after immigration in more recent US immigrants from Cuba.

    Science.gov (United States)

    Damas, O M; Avalos, D J; Palacio, A M; Gomez, L; Quintero, M A; Deshpande, A R; Sussman, D A; McCauley, J L; Lopez, J; Schwartz, S J; Abreu, M T

    2017-08-01

    Despite a rising incidence of inflammatory bowel disease (IBD) in Hispanics in the United States, there are no studies examining the relationship between immigrant generation and IBD onset among Hispanics. To determine whether age of IBD diagnosis, time from immigration to IBD diagnosis and IBD phenotype, differed across immigration periods in South Florida Cuban immigrants. This was a cohort of consecutively identified Cuban-born adults who developed IBD in the United States and were followed in gastroenterology (GI) clinic. We divided time cohorts of immigration by historical relevance: before 1980, 1980-1994 and 1995-to-present. We examined differences across time cohorts in diagnosis age, time from immigration to IBD diagnosis, and IBD phenotype (ie, IBD type, disease location). A total of 130 Cuban patients with IBD were included. Age of IBD diagnosis was older in Cubans arriving before 1980 than in those arriving between 1980-1994 or after 1995 (44.7 vs 33.79 and 33.71, respectively, Pimmigration and diagnosis was shorter in patients arriving to the US after 1980 (31.77 years, Standard deviation (SD) 12.83 (immigration in Cubans, suggesting that environmental changes either in the United States, Cuba or both are resulting in faster IBD onset in younger immigrant generations. These studies can inform the search for environmental triggers that may result in IBD. © 2017 John Wiley & Sons Ltd.

  3. Crime story: the role of crime and immigration in the anti-immigration vote

    NARCIS (Netherlands)

    Dinas, E.; van Spanje, J.

    2011-01-01

    Some scholars have found that mass immigration fuels the success of anti-immigration parties, whereas others have found that it does not. In this paper, we propose a reason for these contradictory results. We advance a set of hypotheses that revolves around a commonly ignored factor, crime. To test

  4. Immigration beyond Ellis Island: Suggestions for Teaching about Immigration in the Now

    Science.gov (United States)

    Hossain, Kazi I.

    2014-01-01

    America's history books abound with stories of immigrants who contributed to the development of this country. In terms of social studies curriculum, all states require schools to teach about immigration. However, the question is how to teach this topic in a manner that will give students--elementary through high school--a better understanding of…

  5. The deterioration of Canadian immigrants' oral health: analysis of the Longitudinal Survey of Immigrants to Canada.

    Science.gov (United States)

    Calvasina, Paola; Muntaner, Carles; Quiñonez, Carlos

    2015-10-01

    To examine the effect of immigration on the self-reported oral health of immigrants to Canada over a 4-year period. The study used Statistics Canada's Longitudinal Survey of Immigrants to Canada (LSIC 2001-2005). The target population comprised 3976 non-refugee immigrants to Canada. The dependent variable was self-reported dental problems. The independent variables were as follows: age, sex, ethnicity, income, education, perceived discrimination, history of social assistance, social support, and official language proficiency. A generalized estimation equation approach was used to assess the association between dependent and independent variables. After 2 years, the proportion of immigrants reporting dental problems more than tripled (32.6%) and remained approximately the same at 4 years after immigrating (33.3%). Over time, immigrants were more likely to report dental problems (OR = 2.77; 95% CI 2.55-3.02). An increase in self-reported dental problems over time was associated with sex, history of social assistance, total household income, and self-perceived discrimination. An increased likelihood of reporting dental problems occurred over time. Immigrants should arguably constitute an important focus of public policy and programmes aimed at improving their oral health and access to dental care in Canada. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  6. 76 FR 67361 - Visas: Documentation of Immigrants Under the Immigration and Nationality Act, as Amended

    Science.gov (United States)

    2011-11-01

    ... DEPARTMENT OF STATE 22 CFR Part 42 [Public Notice 7391] RIN 1400-AC86 Visas: Documentation of Immigrants Under the Immigration and Nationality Act, as Amended AGENCY: State Department. ACTION: Interim final rule. SUMMARY: This rule amends the Department of State's regulations relating to adoptions in...

  7. Immigration and integration policy and labour market attainment among Scandinavian immigrants

    DEFF Research Database (Denmark)

    Jakobsen, Vibeke; Korpi, Tomas; Lorentzen, Thomas

    Comparing immigrant labour market integration, the OECD ranked the Scandinavian countries Denmark, Norway and Sweden at the bottom. Integration depends on immigration and integration policy, and the countries’ policies have traditionally here been very similar. However, in the early 2000s Denmark......, employment trends in Norway and Sweden were almost as positive without similar earnings penalties, questioning the aptness of the Danish reforms....

  8. Immigration and Citizenship: Participation and Self-organisation of Immigrants in the Veneto (North Italy

    Directory of Open Access Journals (Sweden)

    Claudia Mantovan

    2006-05-01

    Full Text Available The changes related to globalisation and to the increasing presence of immigrants in Western Europe place the traditional concept of citizenship in crisis: formal citizenship is no longer a means to inclusion for an increasing number of people, such as non-EU immigrants. A research project, like the one presented in this paper, which seeks to study immigrants' citizenship demands (MEZZADRA, 2001, needs, therefore, to concentrate on a more pragmatic meaning of citizenship. Partly following the suggestions of some authors who have researched this topic, I have built a multidimensional model for analysing immigrants' self-organisation and political participation in Italy and, in particular, in the Veneto region. The model takes into consideration four factors that can have an influence on immigrants' civic and political participation, namely: 1 supranational and national context, 2 local immigration field, 3 infra-political sphere, cultural background, transnational dimension and 4 some variables related to the individual (like gender, age, length of time in host country, etc. The findings show that these factors are important in shaping "immigrants' citizenship demands" and that for many immigrants formal citizenship is neither a salient issue nor a fundamental tool for participation in the society of arrival. URN: urn:nbn:de:0114-fqs060347

  9. Mental Health Consultation Among Ontario's Immigrant Populations.

    Science.gov (United States)

    Islam, Farah; Khanlou, Nazilla; Macpherson, Alison; Tamim, Hala

    2017-11-16

    To determine the prevalence rates and characteristics of past-year mental health consultation for Ontario's adult (18 + years old) immigrant populations. The Canadian Community Health Survey (CCHS) 2012 was used to calculate the prevalence rates of past-year mental health consultation by service provider type. Characteristics associated with mental health consultation were determined by carrying out multivariable logistic regression analysis on merged CCHS 2008-2012 data. Adult immigrant populations in Ontario (n = 3995) had lower estimated prevalence rates of past-year mental health consultation across all service provider types compared to Canadian-born populations (n = 14,644). Amongst those who reported past-year mental health consultation, 57.89% of Ontario immigrants contacted their primary care physician, which was significantly higher than the proportion who consulted their family doctor from Canadian-born populations (45.31%). The factors of gender, age, racial/ethnic background, education level, working status, food insecurity status, self-perceived health status, smoking status, alcohol drinking status, years since immigration, and age at time of immigration were significantly associated with past-year mental health consultation for immigrant populations. Ontario's adult immigrant populations most commonly consult their family doctor for mental health care. Potential exists for expanding the mental health care role of primary care physicians as well as efforts to increase accessibility of specialized mental health services. Integrated, coordinated care where primary care physicians, specialized mental health professionals, social workers, and community educators, etc. working together in a sort of "one-stop-shop" may be the most effective way to mitigate gaps in the mental health care system. In order to effectively tailor mental health policy, programming, and promotion to suit the needs of immigrant populations initiatives that focus on

  10. Differences in hospital attendance for anaphylaxis between immigrants and non-immigrants

    DEFF Research Database (Denmark)

    Norredam, M.; Sheikh, Aziz; Svendsen, K. Dynnes

    2016-01-01

    Background: The impact of migration on the risk of anaphylaxis remains unknown. We hypothesized that non-Western immigrants have a lower incidence of anaphylaxis compared to Danish-born. We investigated variations in hospital attendance for anaphylaxis between immigrants and Danish-born including...... time- and age- trends. Methods: A register-based, historical prospective cohort design. Refugees or family reunified immigrants (n = 127 250) who, between January 1, 1994 and December 31, 2010, obtained residency permits in Denmark were included and matched in a 1 : 6 ratio on age and sex with Danish......, adjusting for age using a Cox regression model including the influence of duration of residence and age when residence was obtained. Results: In total 1053 hospital attendances for anaphylaxis were identified: 89 among non-Western immigrants, 9 among Western immigrants and 955 among Danish-born patients...

  11. NEIGHBORHOOD IMMIGRANT CONCENTRATION, ACCULTURATION, AND CULTURAL ALIENATION IN FORMER SOVIET IMMIGRANT WOMEN.

    Science.gov (United States)

    Miller, Arlene Michaels; Birman, Dina; Zenk, Shannon; Wang, Edward; Sorokin, Olga; Connor, Jorgia

    2009-01-01

    Several acculturation theories note the importance of surrounding context, but few studies describe neighborhood influences on immigrant adaptation. The purpose of this study was to examine relationships among neighborhood immigrant concentration, acculturation, and alienation for 151 women aged 44-80 from the former Soviet Union who lived in the US fewer than 13 years. Participants resided in 65 census tracts in the Chicago area with varying concentrations of Russian-speaking and diverse immigrants. Results from self-report questionnaires suggest that the effect of acculturation on alienation varies depending on neighborhood characteristics. The study also demonstrates the complexity of individual and contextual influences on immigrant adoption. Understanding these relationships is important for developing community-based and neighborhood-level interventions to enhance the mental health of immigrants.

  12. Centromere replication timing determines different forms of genomic instability in Saccharomyces cerevisiae checkpoint mutants during replication stress.

    Science.gov (United States)

    Feng, Wenyi; Bachant, Jeff; Collingwood, David; Raghuraman, M K; Brewer, Bonita J

    2009-12-01

    Yeast replication checkpoint mutants lose viability following transient exposure to hydroxyurea, a replication-impeding drug. In an effort to understand the basis for this lethality, we discovered that different events are responsible for inviability in checkpoint-deficient cells harboring mutations in the mec1 and rad53 genes. By monitoring genomewide replication dynamics of cells exposed to hydroxyurea, we show that cells with a checkpoint deficient allele of RAD53, rad53K227A, fail to duplicate centromeres. Following removal of the drug, however, rad53K227A cells recover substantial DNA replication, including replication through centromeres. Despite this recovery, the rad53K227A mutant fails to achieve biorientation of sister centromeres during recovery from hydroxyurea, leading to secondary activation of the spindle assembly checkpoint (SAC), aneuploidy, and lethal chromosome segregation errors. We demonstrate that cell lethality from this segregation defect could be partially remedied by reinforcing bipolar attachment. In contrast, cells with the mec1-1 sml1-1 mutations suffer from severely impaired replication resumption upon removal of hydroxyurea. mec1-1 sml1-1 cells can, however, duplicate at least some of their centromeres and achieve bipolar attachment, leading to abortive segregation and fragmentation of incompletely replicated chromosomes. Our results highlight the importance of replicating yeast centromeres early and reveal different mechanisms of cell death due to differences in replication fork progression.

  13. Mad2 binding to Mad1 and Cdc20, rather than oligomerization, is required for the spindle checkpoint

    DEFF Research Database (Denmark)

    Sironi, L; Melixetian, M; Faretta, M

    2001-01-01

    Mad2 is a key component of the spindle checkpoint, a device that controls the fidelity of chromosome segregation in mitosis. The ability of Mad2 to form oligomers in vitro has been correlated with its ability to block the cell cycle upon injection into Xenopus embryos. Here we show that Mad2 forms...

  14. Structural Biology of the Immune Checkpoint Receptor PD-1 and Its Ligands PD-L1/PD-L2

    NARCIS (Netherlands)

    Zak, Krzysztof M.; Grudnik, Przemyslaw; Magiera, Katarzyna; Dömling, Alexander; Dubin, Grzegorz; Holak, Tad A.

    2017-01-01

    Cancer cells can avoid and suppress immune responses through activation of inhibitory immune checkpoint proteins, such as PD-1, PD-L1, and CTLA-4. Blocking the activities of these proteins with monoclonal antibodies, and thus restoring T cell function, has delivered breakthrough therapies against

  15. ATM/Wip1 activities at chromatin control Plk1 re-activation to determine G2 checkpoint duration

    Czech Academy of Sciences Publication Activity Database

    Jaiswal, H.; Benada, Jan; Müllers, E.; Akopyan, K.; Burdová, Kamila; Koolmeister, T.; Helleday, T.; Medema, R.H.; Macůrek, Libor; Lindqvist, A.

    2017-01-01

    Roč. 36, č. 14 (2017), s. 2161-2176 ISSN 0261-4189 R&D Projects: GA ČR GA13-18392S Institutional support: RVO:68378050 Keywords : ATM * ATR * checkpoint recovery * G2 * Pik1 Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Cell biology Impact factor: 9.792, year: 2016

  16. Wip1 phosphatase is associated with chromatin and dephosphorylates gammaH2AX to promote checkpoint inhibition

    Czech Academy of Sciences Publication Activity Database

    Macůrek, Libor; Lindqvist, A.; Voets, O.; Kool, J.; Vos, H.R.; Medema, R.H.

    2010-01-01

    Roč. 29, č. 15 (2010), s. 2281-2291 ISSN 0950-9232 R&D Projects: GA ČR GPP305/10/P420 Institutional research plan: CEZ:AV0Z50520514 Keywords : DNA damage * checkpoint * phosphatase Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 7.414, year: 2010

  17. Design Optimization of Time- and Cost-Constrained Fault-Tolerant Embedded Systems with Checkpointing and Replication

    DEFF Research Database (Denmark)

    Pop, Paul; Izosimov, Viacheslav; Eles, Petru

    2009-01-01

    We present an approach to the synthesis of fault-tolerant hard real-time systems for safety-critical applications. We use checkpointing with rollback recovery and active replication for tolerating transient faults. Processes and communications are statically scheduled. Our synthesis approach deci...

  18. ProAtlantic - The Atlantic Checkpoint - Data Availability and Adequacy in the Atlantic Basin

    Science.gov (United States)

    McGrath, F.

    2017-12-01

    DG MAREs Atlantic Checkpoint is a basin scale wide monitoring system assessment activity based upon targeted end-user applications. It is designed to be a benchmark for the assessment of hydrographic, geological, habitat, climate and fisheries data existence and availability in the Atlantic basin. DG MAREs Atlantic Checkpoint service will be delivered by the ProAtlantic project. The objective of this project is to investigate, through appropriate methodologies in the framework of 11 key marine challenges, how current international and national data providers - e.g. EMODNet, Copernicus - meet the requirements of the stakeholders and deliver fit for purpose data. By so doing, the main thematic and geographic gaps will be readily identified in the Atlantic basin for future consideration by DG MARE. For each challenge, specific web products in the form of maps, metadata, spreadsheets and reports will be delivered. These products are not an end by themselves but rather a means of showing whether data were available, let alone accessible. For example, the Fisheries Impact Challenge outputs include data grids (VMS/Seabed) and data adequacy reports. Production of gridded data layers in order to show the extent of fisheries impact on the seafloor involved the identification, acquisition and collation of data sources for the required data types (VMS/Seabed/Habitats Data) in the Atlantic basin. The resulting spatial coverage of these grids indicates the relatively low level of data availability and adequacy across the Atlantic basin. Aside from the data delivered by programmes such as EMODNet and Copernicus, there are a lot of initiatives by regional bodies such as OSPAR and ICES that consist of assembling and disseminating data to address specific issues. Several international projects have delivered research, data collection, and networking around several of the Atlantic Checkpoint challenge topics, namely MPAs, renewable energy assessment, seabed mapping, oil spill

  19. Radiation-induced apoptosis and cell cycle checkpoints in human colorectal tumour cell lines

    International Nuclear Information System (INIS)

    Playle, L.C.

    2001-03-01

    The p53 tumour suppressor gene is mutated in 75% of colorectal carcinomas and is critical for DNA damage-induced G1 cell cycle arrest. Data presented in this thesis demonstrate that after treatment with Ionizing Radiation (IR), colorectal tumour cell lines with mutant p53 are unable to arrest at G1 and undergo cell cycle arrest at G2. The staurosporine derivative, UCN-01, was shown to abrogate the IR-induced G2 checkpoint in colorectal tumour cell lines. Furthermore, in some cell lines, abrogation of the G2 checkpoint was associated with radiosensitisation. Data presented in this study demonstrate that 2 out of 5 cell lines with mutant p53 were sensitised to IR by UCN-01. In order to determine whether radiosensitisation correlated with lack of functional p53, transfected derivatives of an adenoma-derived cell line were studied, in which endogenous wild type p53 was disrupted by expression of a dominant negative p53 mutant protein (and with a vector control). In both these cell lines UCN-01 abrogated the G2 arrest however this was not associated with radiosensitisation, indicating that radiosensitisation is a cell type-specific phenomenon. Although 2 colorectal carcinoma cell lines, with mutant p53, were sensitised to IR by UCN-01, the mechanisms of p53-independent IR-induced apoptosis in the colon are essentially unknown. The mitogen-activated protein kinase (MAPK) pathways (that is the JNK, p38 and ERK pathways) have been implicated in apoptosis in a range of cell systems and in IR-induced apoptosis in some cell types. Data presented in this study show that, although the MAPKs can be activated by the known activator anisomycin, there is no evidence of a role for MAPKs in IR-induced apoptosis in colorectal tumour cell lines, regardless of p53 status. In summary, some colorectal tumour cell lines with mutant p53 can be sensitised to IR-induced cell death by G2 checkpoint abrogation and this may be an important treatment strategy, however mechanisms of IR-induced p53

  20. Divorce and immigration: the social integration of immigrant divorcees in Israel.

    Science.gov (United States)

    Damian, N

    1985-12-01

    This paper attempts to supply information on what motivated some 7000 Jewish divorcees to leave their countries of origin in the last decade and settle in Israel. The study also examines the differences in social integration of immigrant divorcees who came to Israel from different political systems--authoritarian or democratic regimes. Finally, the study examines the extent to which immigrant divorcees, who generally arrive in Israel with children, are to be considered as a "high risk" social group requiring special attention and particular aid. Of the 287,487 immigrants aged 15 years and over who arrived in Israel between 1970-1980, 53.7% were women (sex ratio: 860 males per 1000 females), and 3.6% were divorced. The findings indicate that there are significant differences between divorcees from Anglophone and Eastern European countries in their motivation for immigrating to Israel. The former decide to immigrate primarily for individual reasons--generally after divorce--expecting that immigration will increase chances of remarriage. In contrast, those who came from Eastern Europe are motivated by political, economic, and ideological reasons; the issue of immigration often sparks the divorce crisis. Divorcees from Anglophone countries are less socially isolated, more likely to meet veteran Israelis, and more satisfied with their life in Israel. Eastern European divorcees usually restrict their social contact to encounters with other immigrants from their country of origin, are less satisfied with their life in Israel, and feel themselves more isolated and frustrated. Despite the difficulties encountered by this group, it was found that there are no marked differences between divorcees and married immigrant women in social integration. In Israel, immigrant divorcees cannot be considered as a "high risk" social group.

  1. The Relationship Between Immigrant School Composition, Classmate Support and Involvement in Physical Fighting and Bullying among Adolescent Immigrants and Non-immigrants in 11 Countries

    DEFF Research Database (Denmark)

    Walsh, Sophie D; De Clercq, Bart; Molcho, Michal

    2016-01-01

    Increasing numbers of migrant youth around the world mean growing numbers of heterogeneous school environments in many countries. Contradictory findings regarding the relationship between immigrant school composition (the percentage of immigrant versus non-immigrant students in a school) and adol...... influences levels of peer violence. The results highlight a need for school intervention programs encouraging positive relations in schools with immigrant populations.......) and adolescent peer violence necessitate further consideration. The current study examined the relationship between immigrant school composition and peer violence, considering classmate support as a potential moderator among 51,636 adolescents (50.1 % female) from 11 countries. The findings showed that a higher...

  2. Higher education and children in immigrant families.

    Science.gov (United States)

    Baum, Sandy; Flores, Stella M

    2011-01-01

    The increasing role that immigrants and their children, especially those from Latin America, are playing in American society, Sandy Baum and Stella Flores argue, makes it essential that as many young newcomers as possible enroll and succeed in postsecondary education. Immigrant youths from some countries find the doors to the nation's colleges wide open. But other groups, such as those from Latin America, Laos, and Cambodia, often fail to get a postsecondary education. Immigration status itself is not a hindrance. The characteristics of the immigrants, such as their country of origin, race, and parental socioeconomic status, in addition to the communities, schools, and legal barriers that greet them in the United States, explain most of that variation. Postsecondary attainment rates of young people who come from low-income households and, regardless of income or immigration status, whose parents have no college experience are low across the board. Exacerbating the financial constraints is the reality that low-income students and those whose parents have little education are frequently ill prepared academically to succeed in college. The sharp rise in demand for skilled labor over the past few decades has made it more urgent than ever to provide access to postsecondary education for all. And policy solutions, say the authors, require researchers to better understand the differences among immigrant groups. Removing barriers to education and to employment opportunities for undocumented students poses political, not conceptual, problems. Providing adequate funding for postsecondary education through low tuition and grant aid is also straightforward, if not easy to accomplish. Assuring that Mexican immigrants and others who grow up in low-income communities have the opportunity to prepare themselves academically for college is more challenging. Policies to improve the elementary and secondary school experiences of all children are key to improving the postsecondary

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

    Science.gov (United States)

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

    2017-01-01

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

  4. Clonal neoantigens elicit T cell immunoreactivity and sensitivity to immune checkpoint blockade

    Science.gov (United States)

    McGranahan, Nicholas; Furness, Andrew J. S.; Rosenthal, Rachel; Ramskov, Sofie; Lyngaa, Rikke; Saini, Sunil Kumar; Jamal-Hanjani, Mariam; Wilson, Gareth A.; Birkbak, Nicolai J.; Hiley, Crispin T.; Watkins, Thomas B. K.; Shafi, Seema; Murugaesu, Nirupa; Mitter, Richard; Akarca, Ayse U.; Linares, Joseph; Marafioti, Teresa; Henry, Jake Y.; Van Allen, Eliezer M.; Miao, Diana; Schilling, Bastian; Schadendorf, Dirk; Garraway, Levi A.; Makarov, Vladimir; Rizvi, Naiyer A.; Snyder, Alexandra; Hellmann, Matthew D.; Merghoub, Taha; Wolchok, Jedd D.; Shukla, Sachet A.; Wu, Catherine J.; Peggs, Karl S.; Chan, Timothy A.; Hadrup, Sine R.; Quezada, Sergio A.; Swanton, Charles

    2016-01-01

    As tumors grow, they acquire mutations, some of which create neoantigens that influence the response of patients to immune checkpoint inhibitors. We explored the impact of neoantigen intratumor heterogeneity (ITH) on antitumor immunity. Through integrated analysis of ITH and neoantigen burden, we demonstrate a relationship between clonal neoantigen burden and overall survival in primary lung adenocarcinomas. CD8+ tumor-infiltrating lymphocytes reactive to clonal neoantigens were identified in early-stage non–small cell lung cancer and expressed high levels of PD-1. Sensitivity to PD-1 and CTLA-4 blockade in patients with advanced NSCLC and melanoma was enhanced in tumors enriched for clonal neoantigens. T cells recognizing clonal neoantigens were detectable in patients with durable clinical benefit. Cytotoxic chemotherapy–induced subclonal neoantigens, contributing to an increased mutational load, were enriched in certain poor responders. These data suggest that neoantigen heterogeneity may influence immune surveillance and support therapeutic developments targeting clonal neoantigens. PMID:26940869

  5. Mitosis-specific phosphorylation of PML at T409 regulates spindle checkpoint.

    Science.gov (United States)

    Jin, J; Liu, J

    2016-08-31

    During mitosis, Promyelocytic leukemia nuclear bodies (PML NBs) change dramatically in morphology and composition, but little is known about function of PML in mitosis. Here, we show that PML is phosphorylated at T409 (PML p409) in a mitosis-specific manner. More importantly, PML p409 contributes to maintain the duration of pro-metaphase and regulates spindle checkpoint. Deficient PML p409 caused a shortening of pro-metaphase and challenged the nocodazole-triggered mitotic arrest. T409A mutation led to a higher frequency of misaligned chromosomes on metaphase plate, and subsequently death in late mitosis. In addition, inhibition of PML p409 repressed growth of tumor cells, suggesting that PML p409 is a potential target for cancer therapy. Collectively, our study demonstrated an important phosphorylated site of PML, which contributed to explore the role of PML in mitosis.

  6. A direct role of Mad1 in the spindle assembly checkpoint beyond Mad2 kinetochore recruitment

    DEFF Research Database (Denmark)

    Kruse, Thomas; Larsen, Marie Sofie Yoo; Sedgwick, Garry G

    2014-01-01

    in the SAC beyond recruitment of C-Mad2 to kinetochores has not yet been addressed. Here, we show that Mad1 is required for mitotic arrest even when C-Mad2 is artificially recruited to kinetochores, indicating that it has indeed an additional function in promoting the checkpoint. The C-terminal globular...... domain of Mad1 and conserved residues in this region are required for this unexpected function of Mad1........ The conversion of O-Mad2 into C-Mad2 at unattached kinetochores is thought to be a key step in activating the SAC. The "template model" proposes that this is achieved by the recruitment of soluble O-Mad2 to C-Mad2 bound at kinetochores through its interaction with Mad1. Whether Mad1 has additional roles...

  7. The Aurora B kinase in chromosome biorientation and spindle checkpoint signalling

    Directory of Open Access Journals (Sweden)

    Veronica eKrenn

    2015-10-01

    Full Text Available Aurora B, a member of the Aurora family of serine/threonine protein kinases, is a key player in chromosome segregation. As part of a macromolecular complex known as the chromosome passenger complex, Aurora B concentrates early during mitosis in the proximity of centromeres and kinetochores, the sites of attachment of chromosomes to spindle microtubules. There, it contributes to a number of processes that impart fidelity to cell division, including kinetochore stabilization, kinetochore-microtubule attachment, and the regulation of a surveillance mechanism named the spindle assembly checkpoint. In the regulation of these processes, Aurora B is the fulcrum of a remarkably complex network of interactions that feed back on its localization and activation state. In this review we discuss the multiple roles of Aurora B during mitosis, focusing in particular on its role at centromeres and kinetochores. Many details of the network of interactions at these locations remain poorly understood, and we focus here on several crucial outstanding questions.

  8. Arabidopsis ARGONAUTE7 selects miR390 through multiple checkpoints during RISC assembly.

    Science.gov (United States)

    Endo, Yayoi; Iwakawa, Hiro-oki; Tomari, Yukihide

    2013-07-01

    Plant ARGONAUTE7 (AGO7) assembles RNA-induced silencing complex (RISC) specifically with miR390 and regulates the auxin-signalling pathway via production of TAS3 trans-acting siRNAs (tasiRNAs). However, how AGO7 discerns miR390 among other miRNAs remains unclear. Here, we show that the 5' adenosine of miR390 and the central region of miR390/miR390* duplex are critical for the specific interaction with AGO7. Furthermore, despite the existence of mismatches in the seed and central regions of the duplex, cleavage of the miR390* strand is required for maturation of AGO7-RISC. These findings suggest that AGO7 uses multiple checkpoints to select miR390, thereby circumventing promiscuous tasiRNA production.

  9. Immune checkpoint inhibitors and targeted therapies for metastatic melanoma: A network meta-analysis.

    Science.gov (United States)

    Pasquali, Sandro; Chiarion-Sileni, Vanna; Rossi, Carlo Riccardo; Mocellin, Simone

    2017-03-01

    Immune checkpoint inhibitors and targeted therapies, two new class of drugs for treatment of metastatic melanoma, have not been compared in randomized controlled trials (RCT). We quantitatively summarized the evidence and compared immune and targeted therapies in terms of both efficacy and toxicity. A comprehensive search for RCTs of immune checkpoint inhibitors and targeted therapies was conducted to August 2016. Using a network meta-analysis approach, treatments were compared with each other and ranked based on their effectiveness (as measured by the impact on progression-free survival [PFS]) and acceptability (the inverse of high grade toxicity). Twelve RCTs enrolling 6207 patients were included. Network meta-analysis generated 15 comparisons. Combined BRAF and MEK inhibitors were associated with longer PFS as compared to anti-CTLA4 (HR: 0.22; 95% confidence interval [CI]: 0.12-0.41) and anti-PD1 antibodies alone (HR: 0.38; CI: 0.20-0.72). However, anti-PD1 monoclonal antibodies were less toxic than anti-CTLA4 monoclonal antibodies (RR: 0.65; CI: 0.40-0.78) and their combination significantly increased toxicity compared to either single agent anti-CTLA4 (RR: 2.06; CI: 1.45-2.93) or anti-PD1 monoclonal antibodies (RR: 3.67; CI: 2.27-5.96). Consistently, ranking analysis suggested that the combination of targeted therapies is the most effective strategy, whereas single agent anti-PD1 antibodies have the best acceptability. The GRADE level of evidence quality for these findings was moderate to low. The simultaneous inhibition of BRAF and MEK appears the most effective treatment for melanomas harboring BRAF V600 mutation, although anti-PD1 antibodies appear to be less toxic. Further research is needed to increase the quality of evidence. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. An Archaeosome-Adjuvanted Vaccine and Checkpoint Inhibitor Therapy Combination Significantly Enhances Protection from Murine Melanoma

    Directory of Open Access Journals (Sweden)

    Felicity C. Stark

    2017-10-01

    Full Text Available Archaeosomes constitute archaeal lipid vesicle vaccine adjuvants that evoke a strong CD8+ T cell response to antigenic cargo. Therapeutic treatment of murine B16-ovalbumin (B16-OVA melanoma with archaeosome-OVA eliminates small subcutaneous solid tumors; however, they eventually resurge despite an increased frequency of circulating and tumor infiltrating OVA-CD8+ T cells. Herein, a number of different approaches were evaluated to improve responses, including dose number, interval, and the combination of vaccine with checkpoint inhibitors. Firstly, we found that tumor protection could not be enhanced by repetitive and/or delayed boosting to maximize the CD8+ T cell number and/or phenotype. The in vivo cytotoxicity of vaccine-induced OVA-CD8+ T cells was impaired in tumor-bearing mice. Additionally, tumor-infiltrating OVA-CD8+ T cells had an increased expression of programmed cell death protein-1 (PD-1 compared to other organ compartments, suggesting impaired function. Combination therapy of tumor-bearing mice with the vaccine archaeosome-OVA, and α-CTLA-4 administered concurrently as well as α-PD-1 and an α-PD-L1 antibody administered starting 9 days after tumor challenge given on a Q3Dx4 schedule (days 9, 12, 15 and 18, significantly enhanced survival. Following multi-combination therapy ~70% of mice had rapid tumor recession, with no detectable tumor mass after >80 days in comparison to a median survival of 17–22 days for untreated or experimental groups receiving single therapies. Overall, archaeosomes offer a powerful platform for delivering cancer antigens when used in combination with checkpoint inhibitor immunotherapies.

  11. The Checkpoint Kinase 1 Inhibitor Prexasertib Induces Regression of Preclinical Models of Human Neuroblastoma.

    Science.gov (United States)

    Lowery, Caitlin D; VanWye, Alle B; Dowless, Michele; Blosser, Wayne; Falcon, Beverly L; Stewart, Julie; Stephens, Jennifer; Beckmann, Richard P; Bence Lin, Aimee; Stancato, Louis F

    2017-08-01

    Purpose: Checkpoint kinase 1 (CHK1) is a key regulator of the DNA damage response and a mediator of replication stress through modulation of replication fork licensing and activation of S and G 2 -M cell-cycle checkpoints. We evaluated prexasertib (LY2606368), a small-molecule CHK1 inhibitor currently in clinical testing, in multiple preclinical models of pediatric cancer. Following an initial assessment of prexasertib activity, this study focused on the preclinical models of neuroblastoma. Experimental Design: We evaluated the antiproliferative activity of prexasertib in a panel of cancer cell lines; neuroblastoma cell lines were among the most sensitive. Subsequent Western blot and immunofluorescence analyses measured DNA damage and DNA repair protein activation. Prexasertib was investigated in several cell line-derived xenograft mouse models of neuroblastoma. Results: Within 24 hours, single-agent prexasertib promoted γH2AX-positive double-strand DNA breaks and phosphorylation of DNA damage sensors ATM and DNA-PKcs, leading to neuroblastoma cell death. Knockdown of CHK1 and/or CHK2 by siRNA verified that the double-strand DNA breaks and cell death elicited by prexasertib were due to specific CHK1 inhibition. Neuroblastoma xenografts rapidly regressed following prexasertib administration, independent of starting tumor volume. Decreased Ki67 and increased immunostaining of endothelial and pericyte markers were observed in xenografts after only 6 days of exposure to prexasertib, potentially indicating a swift reduction in tumor volume and/or a direct effect on tumor vasculature. Conclusions: Overall, these data demonstrate that prexasertib is a specific inhibitor of CHK1 in neuroblastoma and leads to DNA damage and cell death in preclinical models of this devastating pediatric malignancy. Clin Cancer Res; 23(15); 4354-63. ©2017 AACR . ©2017 American Association for Cancer Research.

  12. Engaging Youth and Pre-Service Teachers in Immigration Deliberations

    Science.gov (United States)

    Daniel, Shannon M.

    2015-01-01

    In this report of innovative teacher practice, the author describes an arts-based event which brought together adolescent refugee and immigrant students and pre-service teachers to deliberate about immigration policies and attitudes in the United States.

  13. Organizations working with Latina immigrants : resources and strategies for change.

    Science.gov (United States)

    2011-01-01

    Over the last several decades, the immigrant population in the United States has experienced : rapid growth, particularly among new immigrants from Latin America. This increase : in migration has significantly altered the social and economic landscap...

  14. The Dark Side of Illegal Immigration: Cause for National Concern

    National Research Council Canada - National Science Library

    Brown, Vicki A

    2007-01-01

    America is a country built on the backbones of immigrants. Unfortunately, to preserve this tradition, the government has allowed individuals to circumvent the immigration system and slip into our borders...

  15. Genetic Control of the Trigger for the G2/M Checkpoint

    Energy Technology Data Exchange (ETDEWEB)

    Hall, Eric J. [Columbia University; Smilenov, Lubomir B. [Columbia University; Young, Erik F. [Columbia University

    2013-10-01

    The work undertaken in this project addressed two seminal areas of low dose radiation biology that are poorly understood and controversial. These areas are the challenge to the linear-no-threshold (LNT) paradigm at low doses of radiation and, the fundamental elements of radiation bystander effect biology Genetic contributions to low dose checkpoint engagement: The LNT paradigm is an extrapolation of known, measured cancer induction endpoints. Importantly, data for lower doses is often not available. Debatably, radiation protection standards have been introduced which are prudently contingent on the adherence of cancer risk to the established trend seen at higher doses. Intriguing findings from other labs have hinted at separate DNA damage response programs that engage at low or high levels of radiation. Individual radiation sensitivity commensurate with hemizygosity for a radiation sensitivity gene has been estimated at 1-2% in the U.S.. Careful interrogation of the DNA damage response at low doses of radiation became important and served as the basis for this grant. Several genes were tested in combinations to determine if combined haploinsufficiency for multiple radiosensitizing genes could render a cell more sensitive to lower levels of acute radiation exposure. We measured a classical radiation response endpoint, cell cycle arrest prior to mitosis. Mouse embryo fibroblasts were used and provided a uniform, rapidly dividing and genetically manipulable population of study. Our system did not report checkpoint engagement at acute doses of gamma rays below 100 mGy. The system did report checkpoint engagement reproducibly at 500 mGy establishing a threshold for activation between 100 and 500 mGy. Engagement of the checkpoint was ablated in cells nullizygous for ATM but was otherwise unperturbed in cells combinatorially haploinsufficient for ATM and Rad9, ATM and PTEN or PTEN and Rad9. Taken together, these experiments tell us that, in a sensitive fibroblast culture

  16. Hepatitis B ESL education for Asian immigrants.

    Science.gov (United States)

    Taylor, Vicky M; Gregory Hislop, T; Bajdik, Christopher; Teh, Chong; Lam, Wendy; Acorda, Elizabeth; Li, Lin; Yasui, Yutaka

    2011-02-01

    Asian communities in North America include large numbers of immigrants with limited English proficiency. Hepatitis B virus (HBV) infection is endemic in most Asian countries and, therefore, Asian immigrant groups have high rates of chronic HBV infection. We conducted a group-randomized trial to evaluate the effectiveness of a hepatitis B English as a second language (ESL) educational curriculum for Asian immigrants. Eighty ESL classes were randomized to experimental (hepatitis B education) or control (physical activity education) status. Students who reported they had not received a HBV test (at baseline) completed a follow-up survey 6 months after randomization. The follow-up survey assessed recent HBV testing and HBV-related knowledge. Provider reports were used to verify self-reported HBV tests. The study group included 218 students who reported they had not been tested for HBV. Follow-up surveys were completed by 180 (83%) of these students. Provider records verified HBV testing for 6% of the experimental group students and 0% of the control group students (P = 0.02). Experimental group students were significantly (P ESL curriculum had a meaningful impact on HBV-related knowledge and a limited impact on HBV testing levels. Future research should evaluate the effectiveness of ESL curricula for other immigrant groups and other health topics, as well as other intervention approaches to increasing levels of HBV testing in Asian immigrant communities.

  17. A preventive groupwork intervention with new immigrants to Israel.

    Science.gov (United States)

    Roskin, M

    1986-03-01

    The act of immigration brings with it numerous major life changes and requires considerable social readjustment. Immigrants are, however, seldom offered specific training in how to effectively interact in a new culture. This paper describes an initial preventive groupwork effort to help English-speaking immigrants living in an Israeli absorption center to adjust successfully to life in a new culture. Suggestions for future preventive interventions with immigrants are considered.

  18. Immigration and the American Industrial Revolution From 1880 to 1920

    OpenAIRE

    Hirschman, Charles; Mogford, Elizabeth

    2009-01-01

    In this study, we measure the contribution of immigrants and their descendents to the growth and industrial transformation of the American workforce in the age of mass immigration from 1880 to 1920. The size and selectivity of the immigrant community, as well as their disproportionate residence in large cities, meant they were the mainstay of the American industrial workforce. Immigrants and their children comprised over half of manufacturing workers in 1920, and if the third generation (the ...

  19. Immigration and Intergenerational Mobility in Metropolitan Los Angeles (IIMMLA)

    OpenAIRE

    Rumbaut, RG

    2008-01-01

    IIMMLA was supported by the Russell Sage Foundation. Since 1991, the Russell Sage Foundation has funded a program of research aimed at assessing how well the young adult offspring of recent immigrants are faring as they move through American schools and into the labor market. Two previous major studies have begun to tell us about the paths to incorporation of the children of contemporary immigrants: The Children of Immigrants Longitudinal Study (CILS), and the Immigrant Second Generation in N...

  20. Immigration and labor productivity: New empirical evidence for Spain

    OpenAIRE

    Nicodemo, Catia

    2013-01-01

    The purpose of this paper of this paper is to explore the immigration and productivity in Spain. We estimate the effect of immigration on labor productivity from 2004 until 2008 for Spain. Using firms (SABI) and individuals data (Social Security Records) we calculate the effect by sector and municipality for the two big Spanish provinces that have received most immigrants in the last decade: Barcelona and Madrid. After controlling for endogeneity of immigration, the results demonstrate that i...

  1. Do immigrants improve the health of native workers?

    OpenAIRE

    Giuntella, Osea

    2014-01-01

    Public debate on immigration focuses on its effects on wages and employment, yet the discussion typically fails to consider the effects of immigration on working conditions that affect workers' health. There is growing evidence that immigrants are more likely than natives to work in risky jobs, as they are more inclined to take on physically intensive tasks. Recent studies show that as immigration rises, native workers are pushed into less demanding jobs. Such market adjustments have positive...

  2. The Effects of Immigration on NHS Waiting Times

    OpenAIRE

    Giuntella, Osea; Nicodemo, Catia; Vargas-Silva, Carlos

    2015-01-01

    This paper analyses the effects of immigration on waiting times in the National Health Service (NHS) in England. Linking administrative records from the Hospital Episode Statistics (2003-2012) with immigration data drawn from the UK Labour Force Survey, we find that immigration reduced waiting times for outpatient referrals and did not have significant effects on waiting times in Accident and Emergency (A&E) and elective care. These results are explained by the fact that immigration increases...

  3. Crime and immigration: new evidence from England and Wales

    OpenAIRE

    Laura Jaitman; Stephen Machin

    2013-01-01

    We study a high profile public policy question on immigration, namely the link between crime and immigration, presenting new evidence from England and Wales in the 2000s. For studying immigration impacts, this period is of considerable interest as the composition of migration to the UK altered dramatically with the accession of Eastern European countries (the A8) to the European Union in 2004. As we show, this has important implications for ensuring a causal impact of immigration can be ident...

  4. Epidemiological Paradox or Immigrant Vulnerability? Obesity Among Young Children of Immigrants

    Science.gov (United States)

    Baker, Elizabeth H.; Rendall, Michael S.; Weden, Margaret M.

    2015-01-01

    According to the “immigrant epidemiological paradox,” immigrants and their children enjoy health advantages over their U.S.-born peers—advantages that diminish with greater acculturation. We investigated child obesity as a potentially significant deviation from this paradox for second-generation immigrant children. We evaluated two alternate measures of mother's acculturation: age at arrival in the United States and English language proficiency. To obtain sufficient numbers of second-generation immigrant children, we pooled samples across two related, nationally representative surveys. Each included measured (not parent-reported) height and weight of kindergartners. We also estimated models that alternately included and excluded mother's pre-pregnancy weight status as a predictor. Our findings are opposite to those predicted by the immigrant epidemiological paradox: children of U.S.-born mothers were less likely to be obese than otherwise similar children of foreign-born mothers; and the children of the least-acculturated immigrant mothers, as measured by low English language proficiency, were the most likely to be obese. Foreign-born mothers had lower (healthier) pre-pregnancy weight than U.S.-born mothers, and this was protective against their second-generation children's obesity. This protection, however, was not sufficiently strong to outweigh factors associated or correlated with the mothers' linguistic isolation and marginal status as immigrants. PMID:26111970

  5. Immigrant Sexual Citizenship: Intersectional Templates among Mexican Gay Immigrants to the United States

    Science.gov (United States)

    Epstein, Steven; Carrillo, Héctor

    2014-01-01

    Existing literature on sexual citizenship has emphasized the sexuality-related claims of de jure citizens of nation-states, generally ignoring immigrants. Conversely, the literature on immigration rarely attends to the salience of sexual issues in understanding the social incorporation of migrants. This article seeks to fill the gap by theorizing and analyzing immigrant sexual citizenship. While some scholars of sexual citizenship have focused on the rights and recognition granted formally by the nation-state and others have stressed more diffuse, cultural perceptions of community and local belonging, we argue that the lived experiences of immigrant sexual citizenship call for multiscalar scrutiny of templates and practices of citizenship that bridge national policies with local connections. Analysis of ethnographic data from a study of 76 Mexican gay and bisexual male immigrants to San Diego, California reveals the specific citizenship templates that these men encounter as they negotiate their intersecting social statuses as gay/bisexual and as immigrants (legal or undocumented); these include an “asylum” template, a “rights” template, and a “local attachments” template. However, the complications of their intersecting identities constrain their capacity to claim immigrant sexual citizenship. The study underscores the importance of both intersectional and multiscalar approaches in research on citizenship as social practice. PMID:25013360

  6. Immigrant Sexual Citizenship: Intersectional Templates among Mexican Gay Immigrants to the United States.

    Science.gov (United States)

    Epstein, Steven; Carrillo, Héctor

    2014-01-01

    Existing literature on sexual citizenship has emphasized the sexuality-related claims of de jure citizens of nation-states, generally ignoring immigrants. Conversely, the literature on immigration rarely attends to the salience of sexual issues in understanding the social incorporation of migrants. This article seeks to fill the gap by theorizing and analyzing immigrant sexual citizenship . While some scholars of sexual citizenship have focused on the rights and recognition granted formally by the nation-state and others have stressed more diffuse, cultural perceptions of community and local belonging, we argue that the lived experiences of immigrant sexual citizenship call for multiscalar scrutiny of templates and practices of citizenship that bridge national policies with local connections. Analysis of ethnographic data from a study of 76 Mexican gay and bisexual male immigrants to San Diego, California reveals the specific citizenship templates that these men encounter as they negotiate their intersecting social statuses as gay/bisexual and as immigrants (legal or undocumented); these include an "asylum" template, a "rights" template, and a "local attachments" template. However, the complications of their intersecting identities constrain their capacity to claim immigrant sexual citizenship. The study underscores the importance of both intersectional and multiscalar approaches in research on citizenship as social practice.

  7. Does acculturation narrow the health literacy gap between immigrants and non-immigrants-An explorative study.

    Science.gov (United States)

    Mantwill, Sarah; Schulz, Peter J

    2017-04-01

    To compare functional health literacy (HL) levels in three immigrant groups to those of the German- and Italian-speaking non-immigrant population in Switzerland. Moreover, to investigate whether language-independent, respectively language-dependent, functional HL and variables of acculturation were associated with self-reported health status among immigrants. Language-independent HL was assessed with the Short Test of Functional Health Literacy (S-TOFHLA) in the respective native languages. Language-dependent HL was measured using Brief Health Literacy Screeners (BHLS) asking about participants' confidence in understanding medical information in the language of the host country. Measures of acculturation included length of stay and age when taking residency in Switzerland. In particular Albanian- and Portuguese-speaking immigrants had lower levels of functional HL. In unadjusted analysis "age when taking residency in Switzerland" was associated with the BHLS. Adjusted analysis showed that the BHLS were significantly associated with self-reported health among all immigrant groups (p≤0.01). Functional HL that is dependent on understanding of medical information in the language of the new host country is a better predictor for self-reported health status among immigrants than language-independent HL. In the clinical setting limited functional HL might be a significant obstacle to successful disease treatment and prevention in immigrants. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  8. Is Temporary Agency Employment a Stepping Stone for Immigrants?

    DEFF Research Database (Denmark)

    Jahn, Elke; Rosholm, Michael

    2013-01-01

    We investigate whether agency employment is a bridge into regular employment for immigrants using the timing-of-events approach. We provide evidence of large positive in-treatment effects for all immigrants. Post-treatment effects are fairly high for male non-western and Eastern European immigrants....

  9. Immigrants' Propensity to Self-Employment: Evidence from Canada.

    Science.gov (United States)

    Li, Peter S.

    2001-01-01

    Uses Canada's Longitudinal Immigration Data Base to highlight patterns of self-employment in various entry cohorts of immigrants between 1980-95 and develop a model to predict immigrants' propensity to self-employment. Overall, arrival in better economic years, longer residence in Canada, higher educational levels, older age, and being selected…

  10. Acculturation Models of Immigrant Soviet Adolescents in Israel

    Science.gov (United States)

    Shamai, Shmuel; Ilatov, Zinaida

    2005-01-01

    This study probed acculturation in Israel of immigrant students from the former USSR from the perception of the host society and the students. The finding from a questionnaire distributed to Israeli-born and immigrant students indicated that most but not all of the Israel-born students applied an assimilatory model while the immigrants were split…

  11. Complicating Culturally Relevant Pedagogy: Unpacking West African Immigrants' Cultural Identities

    Science.gov (United States)

    Allen, Keisha McIntosh; Jackson, Iesha; Knight, Michelle G.

    2012-01-01

    This study presents findings from a case study of 18 second- and 1.5-generation West African immigrants. We draw upon notions of elusive culture and indigenous knowledges to highlight participants' complex cultural identities and respond to anti-immigration discourses through positioning West African immigrant students as assets in American…

  12. Haitian Immigrants in Black America. A Sociological and Sociolinguistic Portrait.

    Science.gov (United States)

    Zephir, Flore

    Identity formation among Haitian immigrants to the United States is explored in an effort to pinpoint the macro (external) and micro (internal) factors that shape the cultural identity of this particular immigrant community. The immigration experience that is revealed is one of a cultural and linguistic identity in transition. Part I presents a…

  13. 8 CFR 235.6 - Referral to immigration judge.

    Science.gov (United States)

    2010-01-01

    ... 8 Aliens and Nationality 1 2010-01-01 2010-01-01 false Referral to immigration judge. 235.6 Section 235.6 Aliens and Nationality DEPARTMENT OF HOMELAND SECURITY IMMIGRATION REGULATIONS INSPECTION OF PERSONS APPLYING FOR ADMISSION § 235.6 Referral to immigration judge. (a) Notice—(1) Referral by Form I...

  14. 8 CFR 341.4 - Surrender of immigration documents.

    Science.gov (United States)

    2010-01-01

    ... 8 Aliens and Nationality 1 2010-01-01 2010-01-01 false Surrender of immigration documents. 341.4... OF CITIZENSHIP § 341.4 Surrender of immigration documents. Each claimant shall surrender any immigration identification and permanent resident cards in his or her possession. [30 FR 5472, Apr. 16, 1965...

  15. 32 CFR 700.860 - Customs and immigration inspections.

    Science.gov (United States)

    2010-07-01

    ... 32 National Defense 5 2010-07-01 2010-07-01 false Customs and immigration inspections. 700.860... Commanding Officer Commanding Officers Afloat § 700.860 Customs and immigration inspections. (a) The... a customs officer or immigration officer of the United States to make on board the ship or aircraft...

  16. Parables and Politics: Clergy Attitudes toward Illegal Immigration in Alabama

    Science.gov (United States)

    Wickersham, Mary Eleanor

    2013-01-01

    The passage of a stringent immigration law in Alabama in 2011 makes relevant the juxtaposition of clergy and congregant attitudes and behaviors toward illegal immigrants as related to Biblical teachings that require charity to aliens. In order to examine the relationship between religious attitudes and illegal immigration, approximately 426…

  17. 8 CFR 1240.12 - Decision of the immigration judge.

    Science.gov (United States)

    2010-01-01

    ... 8 Aliens and Nationality 1 2010-01-01 2010-01-01 false Decision of the immigration judge. 1240.12 Section 1240.12 Aliens and Nationality EXECUTIVE OFFICE FOR IMMIGRATION REVIEW, DEPARTMENT OF JUSTICE IMMIGRATION REGULATIONS PROCEEDINGS TO DETERMINE REMOVABILITY OF ALIENS IN THE UNITED STATES Removal...

  18. 8 CFR 1240.31 - Authority of immigration judges.

    Science.gov (United States)

    2010-01-01

    ... 8 Aliens and Nationality 1 2010-01-01 2010-01-01 false Authority of immigration judges. 1240.31 Section 1240.31 Aliens and Nationality EXECUTIVE OFFICE FOR IMMIGRATION REVIEW, DEPARTMENT OF JUSTICE IMMIGRATION REGULATIONS PROCEEDINGS TO DETERMINE REMOVABILITY OF ALIENS IN THE UNITED STATES Exclusion of...

  19. Immigration, "Any Small Goodness," and Integrated Social Studies

    Science.gov (United States)

    Bauml, Michelle; Field, Sherry L.; Ledbetter, Mary

    2013-01-01

    Mary Ledbetter's fifth grade students at the University of Texas Elementary School know immigration well. Some of them are recent immigrants from Mexico, or they have family members who are. Several of Mary's students are first or second generation Americans. For Mary, immigration is one of the most important units she teaches, one that integrates…

  20. 28 CFR 16.84 - Exemption of Immigration Appeals System.

    Science.gov (United States)

    2010-07-01

    ... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Exemption of Immigration Appeals System... MATERIAL OR INFORMATION Exemption of Records Systems Under the Privacy Act § 16.84 Exemption of Immigration...) Decisions of the Board of Immigration Appeals (JUSTICE/BIA-001). This exemption applies only to the extent...

  1. Challenging Anti-Immigration Discourses in School and Community Contexts

    Science.gov (United States)

    Allexsaht-Snider, Martha; Buxton, Cory A.; Harman, Ruth

    2012-01-01

    Rapid migration shifts, anti-immigrant discourses in the public sphere, and harsh immigration policies have posed daunting challenges for immigrant students, their families, their teachers, and their communities in the 21st century. Trends in public discourse and law enforcement in the United States mirror developments in European countries with…

  2. 8 CFR 1003.0 - Executive Office for Immigration Review.

    Science.gov (United States)

    2010-01-01

    ... 8 Aliens and Nationality 1 2010-01-01 2010-01-01 false Executive Office for Immigration Review. 1003.0 Section 1003.0 Aliens and Nationality EXECUTIVE OFFICE FOR IMMIGRATION REVIEW, DEPARTMENT OF JUSTICE GENERAL PROVISIONS EXECUTIVE OFFICE FOR IMMIGRATION REVIEW § 1003.0 Executive Office for...

  3. 24 CFR 5.510 - Documents of eligible immigration status.

    Science.gov (United States)

    2010-04-01

    ... 24 Housing and Urban Development 1 2010-04-01 2010-04-01 false Documents of eligible immigration... Noncitizens § 5.510 Documents of eligible immigration status. (a) General. A responsible entity shall request and review original documents of eligible immigration status. The responsible entity shall retain...

  4. 76 FR 63321 - U.S. Citizenship and Immigration Services

    Science.gov (United States)

    2011-10-12

    ... DEPARTMENT OF HOMELAND SECURITY U.S. Citizenship and Immigration Services Agency Information... Program. The Department of Homeland Security, U.S. Citizenship and Immigration Services (USCIS) will be... sponsoring the collection: No Agency Form Number; File Number OMB-18. U.S. Citizenship and Immigration...

  5. 24 CFR 5.512 - Verification of eligible immigration status.

    Science.gov (United States)

    2010-04-01

    ... immigration status. 5.512 Section 5.512 Housing and Urban Development Office of the Secretary, Department of... Noncitizens § 5.512 Verification of eligible immigration status. (a) General. Except as described in paragraph...) Primary verification—(1) Automated verification system. Primary verification of the immigration status of...

  6. 8 CFR 1240.50 - Decision of the immigration judge.

    Science.gov (United States)

    2010-01-01

    ... 8 Aliens and Nationality 1 2010-01-01 2010-01-01 false Decision of the immigration judge. 1240.50 Section 1240.50 Aliens and Nationality EXECUTIVE OFFICE FOR IMMIGRATION REVIEW, DEPARTMENT OF JUSTICE IMMIGRATION REGULATIONS PROCEEDINGS TO DETERMINE REMOVABILITY OF ALIENS IN THE UNITED STATES Proceedings To...

  7. The Economics of U.S. Immigration Policy

    Science.gov (United States)

    Orrenius, Pia M.; Zavodny, Madeline

    2012-01-01

    The economic gains from immigration are much like those from international trade: The economy benefits overall from immigration, but there are distributional effects that create both winners and losers. Immigration is different from trade, however, in that the physical presence of the people who provide the goods and services that drive the…

  8. 8 CFR 336.2 - Hearing before an immigration officer.

    Science.gov (United States)

    2010-01-01

    ... 8 Aliens and Nationality 1 2010-01-01 2010-01-01 false Hearing before an immigration officer. 336... HEARINGS ON DENIALS OF APPLICATIONS FOR NATURALIZATION § 336.2 Hearing before an immigration officer. (a..., the Service shall schedule a review hearing before an immigration officer, within a reasonable period...

  9. The Educational Attainment of Second Generation Immigrants in the Netherlands

    NARCIS (Netherlands)

    van Ours, J.C.; Veenman, J.M.C.

    2001-01-01

    Since the mid-1960's the Netherlands has had an immigration surplus, mainly because of manpower recruitment from Turkey and Morocco and immigration from the former Dutch colony of Surinam.Immigrants have a weak labor market position, which is related to their educational level and language

  10. Status of Muslim Immigrants' Children with Learning Difficulties in Vienna

    Science.gov (United States)

    Mohsin, M. Naeem; Shabbir, Muhammad; Saeed, Wizra; Mohsin, M. Saleem

    2013-01-01

    The study was conducted to know the status of Muslim immigrants' children with learning difficulties and importance of parents' involvement for the education whose children are with learning difficulties, and the factors responsible for the learning difficulties among immigrants' children. There were 81 immigrant children with learning…

  11. Gender, Acculturation, Food Patterns, and Overweight in Korean Immigrants

    Science.gov (United States)

    Jasti, Sunitha; Lee, Chang Hyun; Doak, Colleen

    2011-01-01

    Objective: To describe acculturation, food patterns, overweight, and gender differences among Korean immigrants in the United States. Methods: A cross-sectional exploratory survey assessed acculturation, food frequencies, and weight status of 195 Korean immigrants. Results: Acculturated Korean immigrants (score greater than or equal to] 2.5) were…

  12. Immigration and Higher Education: The Crisis and the Opportunities.

    Science.gov (United States)

    Stewart, David W.

    1991-01-01

    Changes in immigration patterns bring problems and opportunities to higher education. New federal law significantly changes the ethnic and skills mix of the immigrant pool. Issues emerging include potential brain drain; pressure for curriculum change; language as a barrier to access; and the rights of illegal immigrants to higher education. (MSE)

  13. Punjabi Orchard Farmers: An Immigrant Enclave in Rural California.

    Science.gov (United States)

    Gibson, Margaret A.

    1988-01-01

    Examines the adaptation patterns of Punjabi Sikh orchard farmers in rural California. Discusses the role of the following: (1) the historical context of immigration; (2) the immigrants' perceptions of their particular situation; (3) the group's cultural traditions; and (4) 1965 Immigration Act. (FMW)

  14. 77 FR 59692 - 2014 Diversity Immigrant Visa Program

    Science.gov (United States)

    2012-09-28

    ... DV program? DVs are intended to provide an immigration opportunity for persons from countries other...)(I) of the Immigration and Nationality Act, as amended, (8 U.S.C. 1151, 1153, and 1154(a)(1)(I)). The... State and conducted based on United States law, specifically Section 203(c) of the Immigration and...

  15. 8 CFR 3.0 - Executive Office for Immigration Review

    Science.gov (United States)

    2010-01-01

    ... 8 Aliens and Nationality 1 2010-01-01 2010-01-01 false Executive Office for Immigration Review 3.0 Section 3.0 Aliens and Nationality DEPARTMENT OF HOMELAND SECURITY GENERAL PROVISIONS EXECUTIVE OFFICE FOR IMMIGRATION REVIEW § 3.0 Executive Office for Immigration Review Regulations of the Executive Office for...

  16. Faculty Member's Guide to U.S. Immigration Law. Revised.

    Science.gov (United States)

    Smith, Eugene H.; Baron, Marvin J.

    Immigration laws and regulations pertaining to foreign students and scholars are summarized as an aid to faculty members. Basic immigration documents and terminology are explained, including the passport, visa, immigration status or classification, Form 1-20 ID, the "green card", and Departure Record. Classes of nonimmigrants are described,…

  17. NEW PERSPECTIVES ON IMMIGRANT CONTEXTS OF RECEPTION

    Science.gov (United States)

    Levitt, Peggy; Cadge, Wendy; Hejtmanek, Jessica; Curran, Sara R.

    2014-01-01

    We argue that important, overlooked differences in what we call the ‘cultural armature’ of Portland, Maine, and Danbury, Connecticut help explain the variation in how each city received new immigrants in recent years. Portland has a long history of contact with the outside world and used its cosmopolitan character to promote urban redevelopment and welcome immigrants from a range of countries of origin. Danbury’s small-town, insular outlook, and the fact that most of its newcomers came from a single country of origin – some without legal documents – made immigrants’ welcome more fragmented. While leaders in both cities speak of multiculturalism and tolerance, the ‘cultural armature’ of each led city leaders to put that talk into action differently. We describe how we see this ‘cultural armature’ at work and argue that it – in combination with demographic realities – led immigrants to be more warmly welcomed in Portland than in Danbury. PMID:25383102

  18. IMMIGRATION GROWTH TENDENCIES IN OECD COUNTRIES

    Directory of Open Access Journals (Sweden)

    Imran SARIHASAN

    2016-12-01

    Full Text Available Immigration became one of the relevant economic topics in recent years. Over the centuries millions of people have migrated, despite the physical, cultural etc. obstacles, to other lands in search of better lives for themselves and their children. In the context of development, globalization and labor market mobility, it is necessary to further analyze the determinants and consequences of migration not only on the host country, but also on the sending country. The increased interest and availability of data keeps this subject in the attention of economists all over the world. In this case an increase in immigration became very significant ıssue for policymakers. The aims of this study are to describe immigration growth tendencies and to answer how much is the average growth rate of foreıgn born population. Thus, in order to measure the native and foreign-born unemployed migrants, twenty-seven OECD countries were used in this research paper.

  19. Immigration and Integration Policy and Labour Market Attainment Among Immigrants to Scandinavia

    DEFF Research Database (Denmark)

    Jakobsen, Vibeke; Lorentzen, Thomas; Korpi, Tomas

    2018-01-01

    Insufficient integration of immigrants into the labour market has been identified as a major problem in the Scandinavian countries Denmark, Norway and Sweden. Integration depends, inter alia, on immigration and integration policy, and for most of the post-war period the policies of the three coun...... that the Danish reforms had any clear-cut effect on either employment or earnings among non-Western immigrants. Moreover, integration in Norway and Sweden was not unequivocally worse despite the absence of similar reforms, raising questions regarding the aptness of the Danish reversal....

  20. Risk of eating disorders in immigrant populations.

    Science.gov (United States)

    Mustelin, L; Hedman, A M; Thornton, L M; Kuja-Halkola, R; Keski-Rahkonen, A; Cantor-Graae, E; Almqvist, C; Birgegård, A; Lichtenstein, P; Mortensen, P B; Pedersen, C B; Bulik, C M

    2017-08-01

    The risk of certain psychiatric disorders is elevated among immigrants. To date, no population studies on immigrant health have addressed eating disorders. We examined whether risk of eating disorders in first- and second-generation immigrants differs from native-born Danes and Swedes. All individuals born 1984-2002 (Danish cohort) and 1989-1999 (Swedish cohort) and residing in the respective country on their 10th birthday were included. They were followed up for the development of eating disorders based on out-patient and in-patient data. The risks of all eating disorder types were lower among first-generation immigrants compared to the native populations: Incidence-rate ratio (95% confidence interval) was 0.39 (0.29, 0.51) for anorexia nervosa, 0.60 (0.42, 0.83) for bulimia nervosa, and 0.62 (0.47, 0.79) for other eating disorders in Denmark and 0.27 (0.21, 0.34) for anorexia nervosa, 0.30 (0.18, 0.51) for bulimia nervosa, and 0.39 (0.32, 0.47) for other eating disorders in Sweden. Likewise, second-generation immigrants by both parents were at lower risk, whereas those with only one foreign-born parent were not. The decreased risk of eating disorders among immigrants is opposite to what has been observed for other psychiatric disorders, particularly schizophrenia. Possible explanations include buffering sociocultural factors and underdetection in health care. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  1. Immigration Stress and Alcohol Use Severity Among Recently Immigrated Hispanic Adults: Examining Moderating Effects of Gender, Immigration Status, and Social Support.

    Science.gov (United States)

    Cano, Miguel Ángel; Sánchez, Mariana; Trepka, Mary Jo; Dillon, Frank R; Sheehan, Diana M; Rojas, Patria; Kanamori, Mariano J; Huang, Hui; Auf, Rehab; De La Rosa, Mario

    2017-03-01

    Identifying and understanding determinants of alcohol use behavior among Hispanic immigrants is an increasingly significant public health concern. Although prior research has examined associations of cultural stressors with alcohol use among Hispanics, few studies have tested these associations among recent adult immigrants. As such, this study aimed to examine (a) the association of immigration stress on alcohol use severity among recently immigrated Hispanic adults (≤ 1 year in the United States) and (b) the moderating effects of gender, immigration status, and social support. A hierarchical multiple regression and moderation analyses were conducted on a sample of 527 participants in South Florida. Results indicated that, after controlling for demographic variables, preimmigration drinking behavior, and dimensions of social support, the association of higher immigration stress with higher alcohol use severity was statistically significant. Moderation analyses indicated that immigration stress had a statistically significant association with alcohol use severity among men, but not women. Also, dimensions of social support consistently reduced the deleterious effect of immigration stress on alcohol use severity. This study adds to the scarce literature on cultural stressors and alcohol use among recent Hispanic immigrants. Findings suggest that it may be important to design gender-specific interventions and that increasing levels of social support may offset the effects of immigration stress on alcohol use. © 2016 Wiley Periodicals, Inc.

  2. Immigrant Integration: Acculturation and Social Integration

    Directory of Open Access Journals (Sweden)

    Astrid HAMBERGER

    2009-11-01

    Full Text Available This article tackles the concept of “immigrant integration” as it is analyzed by different authors in the international migration field. In this article, I will use the terms “refugee” and “immigrant” as equivalent to each other due to the interchangeable character of these concepts throughout the integration literature. First, the article brings into discussion the definitional and conceptual battle around the concept of immigrant “integration”, and second, it will describe and analyze cultural and social integration with their presupposing processes.

  3. Does immigration boost per capita income?

    DEFF Research Database (Denmark)

    Felbermayer, Gabriel; Hiller, Sanne; Sala, Davide

    2010-01-01

    Using a cross-section of countries, we adapt Frankel and Romer's (1999) IV strategy to international labor mobility. Controlling for institutional quality, trade, and financial openness, we establish a robust and non-negative causal effect of immigration on real per capita income.......Using a cross-section of countries, we adapt Frankel and Romer's (1999) IV strategy to international labor mobility. Controlling for institutional quality, trade, and financial openness, we establish a robust and non-negative causal effect of immigration on real per capita income....

  4. Does Immigration Boost Per Capita Income?

    DEFF Research Database (Denmark)

    Felbermayr, Gabriel J.; Hiller, Sanne; Sala, Davide

    Using a cross-section of countries, we adapt Frankel and Romer's (1999) IV strategy to international labor mobility. Controlling for institutional quality, trade, and ?nancial openness, we establish a robust and non-negative causal e?ect of immigration on real per-capita income.......Using a cross-section of countries, we adapt Frankel and Romer's (1999) IV strategy to international labor mobility. Controlling for institutional quality, trade, and ?nancial openness, we establish a robust and non-negative causal e?ect of immigration on real per-capita income....

  5. Immigrants: A Study Case for N. Greece

    Directory of Open Access Journals (Sweden)

    Maria Vlachadi

    2014-05-01

    Full Text Available It is a fact that the phenomenon of immigration constitutes, during the last years, the view of a new social and economic reality for the societies of most western European countries. Greece has received for the first time, during the 1990s, thousands of economic immigrants who appear not only in the big city centers but also in small country towns. Immigrants probably constitute the most discussed issue in the Modern Greek society, in an economic conjuncture in which the economic crisis has functioned in a catalytic way for the diffusion of insecurity in the native population (Biblionet, 2012. The Greek state was not ready to accept such a large number of immigrants in so little time. It showed hesitance and could not keep a steady position as far as the promotion of a necessary institutional framework for their integration in the Greek society was concerned. This initial surprise has never been overcome. In Greece, as well as in the rest of the European South, the majority of the immigrants entering the country illegally have supplied the informal working market. Even when they become legal, the available working positions for them presuppose low specialization with low payments, hard work and limited opportunities of improvement of their social and occupational status. Although the immigration phenomenon is usually approached in a national level, the local level is considered the most suitable one to deal with the interaction of its economic, social, political and cultural dimensions. Recent studies have shown their positive contribution in the revival of Greek agriculture and Greek agricultural districts in general. Within the scale of the Greek community and the degree in which it constitutes a place of constant flow of human resources, it is inevitable the general presence of immigrants to raise issues of mutual infiltrations among different national populations within which there arise interaction issues and intercultural interdependence

  6. Engagement in self-regulated deep learning of successful immigrant and non-immigrant students in inner city schools

    NARCIS (Netherlands)

    Blom, S.; Severiens, S.

    2008-01-01

    In order to examine and explain differences in self-regulated (SR) deep learning of successful immigrant and non-immigrant students we investigated a population of 650 high track 10th grade students in Amsterdam, of which 39% had an immigrant background. By means of a questionnaire based on the MSLQ

  7. A Profile of the Low-Wage Immigrant Workforce. Immigrant Families and Workers. Facts and Perspectives Brief.

    Science.gov (United States)

    Capps, Randy; Fix, Michael; Passel, Jeffrey S.; Ost, Jason; Perez-Lopez, Dan

    Immigrants compose an increasingly large share of the U.S. labor force and growing share of low-wage workers. Immigrants' hourly wages are lower on average than those for natives. Immigrant workers are much more likely than native workers to drop out of high school. Three-fourths of all U.S. workers with less than a ninth grade education are…

  8. 8 CFR 1337.2 - Oath administered by the Immigration and Naturalization Service or an Immigration Judge.

    Science.gov (United States)

    2010-01-01

    ... 8 Aliens and Nationality 1 2010-01-01 2010-01-01 false Oath administered by the Immigration and Naturalization Service or an Immigration Judge. 1337.2 Section 1337.2 Aliens and Nationality EXECUTIVE OFFICE FOR IMMIGRATION REVIEW, DEPARTMENT OF JUSTICE NATIONALITY REGULATIONS OATH OF ALLEGIANCE § 1337.2 Oath...

  9. Immigration - mismatches in labor, housing and space - the effects of immigration of several nationalities with regard to the Netherlands

    NARCIS (Netherlands)

    Musterd, S.; Muus, P.

    1995-01-01

    In the Netherlands, the sharp recent increase of the number of refugee immigrants (asylum seekers) runs parallel to increased numbers of immigrants of other types, Therefore, at least five types of immigrants should still be distinguished (labour migrants, migrants from former colonies, from EU

  10. 8 CFR 337.2 - Oath administered by the Immigration and Naturalization Service or an Immigration Judge.

    Science.gov (United States)

    2010-01-01

    ... 8 Aliens and Nationality 1 2010-01-01 2010-01-01 false Oath administered by the Immigration and Naturalization Service or an Immigration Judge. 337.2 Section 337.2 Aliens and Nationality DEPARTMENT OF HOMELAND SECURITY NATIONALITY REGULATIONS OATH OF ALLEGIANCE § 337.2 Oath administered by the Immigration and...

  11. Language, Ethnicity and Education: Case Studies on Immigrant Minority Groups and Immigrant Minority Languages. Multilingual Matters 111.

    Science.gov (United States)

    Broeder, Peter; Extra, Guus

    Immigrant minority groups and immigrant minority languages in Europe are viewed from three perspectives (demographic, sociolinguistic, and educational) through case studies. The first part, using a demographic approach, includes research on immigrant minority groups in population statistics of both European Union and English-dominant countries…

  12. Being "in a Limbo": Perceptions of Immigration, Identity and Adaptation of Immigrant Students in South Africa and the United States

    Science.gov (United States)

    Catalano, Theresa; Fox, Jill; Vandeyar, Saloshna

    2016-01-01

    Much research is available that details student experiences of immigration and adaptation to receiving countries and schools, but few studies analyze the metaphors used by immigrant students (IS) when talking about the immigration experience, or offer a comparative lens through which to view identity negotiation in two very different contexts. The…

  13. Checks, Balances, and Resistance: The Impact of an Anti-Immigrant Federal Administration on a School for Immigrant Teenagers

    Science.gov (United States)

    Miranda, Chandler P.

    2017-01-01

    The 2016 presidential election was dominated by anti-immigrant rhetoric where truths counted for less than bombast, obscuring the fact that the majority of refugees and immigrants are women and children. This article describes how teachers and students in a school for newly arrived immigrants are adapting to the reality of the new administration.

  14. The subunits of the S-phase checkpoint complex Mrc1/Tof1/Csm3: dynamics and interdependence.

    Science.gov (United States)

    Uzunova, Sonya Dimitrova; Zarkov, Alexander Stefanov; Ivanova, Anna Marianova; Stoynov, Stoyno Stefanov; Nedelcheva-Veleva, Marina Nedelcheva

    2014-01-01

    The S-phase checkpoint aims to prevent cells from generation of extensive single-stranded DNA that predisposes to genome instability. The S. cerevisiae complex Tof1/Csm3/Mrc1 acts to restrain the replicative MCM helicase when DNA synthesis is prohibited. Keeping the replication machinery intact allows restart of the replication fork when the block is relieved. Although the subunits of the Tof1/Csm3/Mrc1 complex are well studied, the impact of every single subunit on the triple complex formation and function needs to be established. This work studies the cellular localization and the chromatin binding of GFP-tagged subunits when the complex is intact and when a subunit is missing. We demonstrate that the complex is formed in cell nucleus, not the cytoplasm, as Tof1, Csm3 and Mrc1 enter the nucleus independently from one another. Via in situ chromatin binding assay we show that a Tof1-Csm3 dimer formation and chromatin binding is required to ensure the attachment of Mrc1 to chromatin. Our study indicates that the translocation into the nucleus is not the process to regulate the timing of chromatin association of Mrc1. We also studied the nuclear behavior of Mrc1 subunit in the process of adaptation to the presence hydroxyurea. Our results indicate that after prolonged HU incubation, cells bypass the S-phase checkpoint and proceed throughout the cell cycle. This process is accompanied by Mrc1 chromatin detachment and Rad53 dephosphorylation. In S. cerevisiae the subunits of the S-phase checkpoint complex Mrc1/Tof1/Csm3 independently enter the cell nucleus, where a Tof1-Csm3 dimer is formed to ensure the chromatin binding of Mrc1 and favor DNA replication and S-phase checkpoint fork arrest. In the process of adaptation to the presence of hydroxyurea Mrc1 is detached from chromatin and Rad53 checkpoint activity is diminished in order to allow S-phase checkpoint escape and completion of the cell cycle.

  15. Comparative Analysis of Immune Checkpoint Molecules and Their Potential Role in the Transmissible Tasmanian Devil Facial Tumor Disease

    Directory of Open Access Journals (Sweden)

    Andrew S. Flies

    2017-05-01

    Full Text Available Immune checkpoint molecules function as a system of checks and balances that enhance or inhibit immune responses to infectious agents, foreign tissues, and cancerous cells. Immunotherapies that target immune checkpoint molecules, particularly the inhibitory molecules programmed cell death 1 and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4, have revolutionized human oncology in recent years, yet little is known about these key immune signaling molecules in species other than primates and rodents. The Tasmanian devil facial tumor disease is caused by transmissible cancers that have resulted in a massive decline in the wild Tasmanian devil population. We have recently demonstrated that the inhibitory checkpoint molecule PD-L1 is upregulated on Tasmanian devil (Sarcophilus harrisii facial tumor cells in response to the interferon-gamma cytokine. As this could play a role in immune evasion by tumor cells, we performed a thorough comparative analysis of checkpoint molecule protein sequences among Tasmanian devils and eight other species. We report that many of the key signaling motifs and ligand-binding sites in the checkpoint molecules are highly conserved across the estimated 162 million years of evolution since the last common ancestor of placental and non-placental mammals. Specifically, we discovered that the CTLA-4 (MYPPPY ligand-binding motif and the CTLA-4 (GVYVKM inhibitory domain are completely conserved across all nine species used in our comparative analysis, suggesting that the function of CTLA-4 is likely conserved in these species. We also found that cysteine residues for intra- and intermolecular disulfide bonds were also highly conserved. For instance, all 20 cysteine residues involved in disulfide bonds in the human 4-1BB molecule were also present in devil 4-1BB. Although many key sequences were conserved, we have also identified immunoreceptor tyrosine-based inhibitory motifs (ITIMs and immunoreceptor tyrosine-based switch

  16. The influence of attitudes toward immigrants on international migration

    DEFF Research Database (Denmark)

    Gorinas, Cedric; Pytlikova, Mariola

    2015-01-01

    We investigate whether anti-immigrant attitudes reduce migrant inflows in OECD countries. Using comprehensive data on international migration and natives’ attitudes, we find that natives’ hostility, when captured with natives’ propensity to discriminate against immigrants on the labor market......, reduces immigration. This effect persists after we control for changes in immigration policies and is stronger for immigrants from OECD countries. Further we show that knowledge of the destination country’s language reinforces the effect. Our results raise a challenge for policy makers in times when...

  17. Immigrants’ Paths to Employment in Finland

    Directory of Open Access Journals (Sweden)

    Aini Pehkonen

    2006-01-01

    Full Text Available The aim of this study was to investigate how immigrants have integrated into Finnish life from the standpoints of employment. The empirical research material consisted of 30 interviews with immigrants and four interviews with of? cials and others dealing with immigrant affairs. Factors promoting employment of immigrants were the voluntary nature of the immigration, educational quali? cations as demonstrated by the relevant certi? cates and knowledge of the Finnish language. One in three reported that they had ? rst received information about vacancies from the Employment Of? ce, and one in ? ve by approaching the employer directly asking for work. One in seven had found out about jobs through friends.

  18. Immigration and Sleep Problems in a Southern European Country: Do Immigrants Get the Best Sleep?

    Science.gov (United States)

    Villarroel, Nazmy; Artazcoz, Lucía

    2017-01-01

    This study analyzes the differences in the prevalence of insomnia symptoms and nonrestorative sleep (NRS) between people born in Spain and immigrants from 7 countries with most immigrants in Spain. Data come from the 2006 Spanish National Health Survey. The sample was composed of all individuals aged 16 to 64 years from Spain and the 7 countries with most immigrants in Spain (N = 22,224). In both sexes, people from Bolivia had a higher prevalence of insomnia symptoms and NRS. Conversely, people from Ecuador, Morocco, and Romania had less insomnia symptoms and NRS than Spanish-born participants. No differences were found between Spanish-born participants and Colombian, Peruvian, and Argentinian women. Poor living conditions in the country of origin and in the host country, discrimination, and culturally related lifestyles could be related to poorer sleep health among Bolivian men. Acculturation may explain the similar sleep health patterns noted between Spanish-born participants and long-term immigrants.

  19. Who is afraid of immigrants? Social predictors of fear of immigrants in Europe

    Directory of Open Access Journals (Sweden)

    Sebastian Năstuţă

    2011-12-01

    Full Text Available Starting from the assumption that „fear” or „the threat feeling” felt on immigrants as a group is a strong predictor of negative reaction and actions against these out-groups we are trying to identify in this paper the social predictors of these feelings. If most studies on anti-immigrant attitudes are oriented mainly to economic effects, city or municipality effects we included in our analysis not only the clasical variable like education, income, age, gender, professional status, citizenship as in previous studies, but also the religious affiliation and immigration descendence. Starting from EVS 2008 data we obtained results that confirms other studies and also we identified the positive strong effect of religious denomination on immigration threat feelings.

  20. How do organizations and social policies 'acculturate' to immigrants? Accommodating skilled immigrants in Canada.

    Science.gov (United States)

    Sakamoto, Izumi; Wei, Yi; Truong, Lele

    2008-12-01

    While the idea of acculturation (Berry 1997) was originally proposed as the mutual change of both parties (e.g., immigrants and the host society), the change processes of host societies are neglected in research. A grounded theory study explored the efforts of human service organizations to 'acculturate' to an increasingly diverse immigrant population, through interviews conducted with service providers serving Mainland Chinese immigrants. Acculturation efforts of human service organizations (mezzo-level acculturation) were often needs-driven and affected by the political will and resultant funding programs (macro-level forces). Even with limitations, human service organizations commonly focused on hiring Mainland Chinese immigrants to reflect the changing demographics of their clientele and creating new programs to meet the language and cultural backgrounds of the clients. To contextualize these organizational efforts, an analysis of how policy changes (macro-level acculturation) interact with organizational practice is presented. Finally, the meaning of acculturation for the host society is discussed.