WorldWideScience

Sample records for causeway immigration checkpoint

  1. 78 FR 25577 - Safety Zone, Figure Eight Causeway Channel; Figure Eight Island, NC

    Science.gov (United States)

    2013-05-02

    ... a private wedding. This action is necessary to protect the life and property of the maritime public... support of a private wedding over the waters of the Figure Eight Causeway Channel. The fireworks will be...

  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 (pexchange, 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. Effects of causeway construction on environment and biota of subtropical tidal flats in Okinawa, Japan.

    Science.gov (United States)

    Reimer, James Davis; Yang, Sung-Yin; White, Kristine N; Asami, Ryuji; Fujita, Kazuhiko; Hongo, Chuki; Ito, Shingo; Kawamura, Iori; Maeda, Isshu; Mizuyama, Masaru; Obuchi, Masami; Sakamaki, Takashi; Tachihara, Katsunori; Tamura, Maiko; Tanahara, Akira; Yamaguchi, Aika; Jenke-Kodama, Holger

    2015-05-15

    Okinawa, Japan is known for its high marine biodiversity, yet little work has been performed on examining impacts of numerous large-scale coastal development projects on its marine ecosystems. Here, we examine apparent impacts of the construction of the Kaichu-Doro causeway, which was built over 40 years ago. The causeway is a 4.75 km long embankment that divides a large tidal flat and has only two points of water exchange along its entire length. We employed quadrats, transects, sampling, visual surveys, and microbial community analyses combined with environmental, water quality data, and 1m cores, at five stations of two paired sites each (one on each side of Kaichu-Doro) to investigate how the environment and biota have changed since the Kaichu-Doro was built. Results indicate reduction in water flow, and site S1 was particularly heavily impacted by poor water quality, with low diversity and disturbed biotic communities. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  4. Water and salt balance of Great Salt Lake, Utah, and simulation of water and salt movement through the causeway, 1987-98

    Science.gov (United States)

    Loving, Brian L.; Miller, Craig W.; Waddell, Kidd M.

    2000-01-01

    The Southern Pacific Transportation Company completed a rock-fill causeway across Great Salt Lake in 1959. The effect of the causeway was to change the water and salt balance of Great Salt Lake by creating two separate but interconnected parts of the lake, with more than 95 percent of freshwater surface inflow entering the lake south of the causeway.The water and salt balance of Great Salt Lake primarily depends on the amount of inflow from tributary streams and the conveyance properties of the causeway that divides the lake into south and north parts. The conveyance properties of the causeway consist of two 15-foot-wide culverts, a 290-foot-wide breach, and permeable rock-fill material.

  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. Compiler-assisted static checkpoint insertion

    Science.gov (United States)

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

    1992-01-01

    This paper describes a compiler-assisted approach for static checkpoint insertion. Instead of fixing the checkpoint location before program execution, a compiler enhanced polling mechanism is utilized to maintain both the desired checkpoint intervals and reproducible checkpoint 1ocations. The technique has been implemented in a GNU CC compiler for Sun 3 and Sun 4 (Sparc) processors. Experiments demonstrate that the approach provides for stable checkpoint intervals and reproducible checkpoint placements with performance overhead comparable to a previously presented compiler assisted dynamic scheme (CATCH) utilizing the system clock.

  7. 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...

  8. 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.

  9. Checkpoint inhibitors in hematological malignancies

    Directory of Open Access Journals (Sweden)

    Chi Young Ok

    2017-05-01

    Full Text Available Abstract Inhibitory molecules such as PD-1, CTLA-4, LAG-3, or TIM-3 play a role to keep a balance in immune function. However, many cancers exploit such molecules to escape immune surveillance. Accumulating data support that their functions are dysregulated in lymphoid neoplasms, including plasma cell myeloma, myelodysplastic syndrome, and acute myeloid leukemia. In lymphoid neoplasms, aberrations in 9p24.1 (PD-L1, PD-L2, and JAK2 locus, latent Epstein-Barr virus infection, PD-L1 3′-untranslated region disruption, and constitutive JAK-STAT pathway are known mechanisms to induce PD-L1 expression in lymphoma cells. Clinical trials demonstrated that PD-1 blockade is an attractive way to restore host’s immune function in hematological malignancies, particularly classical Hodgkin lymphoma. Numerous clinical trials exploring PD-1 blockade as a single therapy or in combination with other immune checkpoint inhibitors in patients with hematologic cancers are under way. Although impressive clinical response is observed with immune checkpoint inhibitors in patients with certain cancers, not all patients respond to immune checkpoint inhibitors. Therefore, to identify best candidates who would have excellent response to checkpoint inhibitors is of utmost importance. Several possible biomarkers are available, but consensus has not been made and pursuit to discover the best biomarker is ongoing.

  10. Checkpoint inhibitors in hematological malignancies.

    Science.gov (United States)

    Ok, Chi Young; Young, Ken H

    2017-05-08

    Inhibitory molecules such as PD-1, CTLA-4, LAG-3, or TIM-3 play a role to keep a balance in immune function. However, many cancers exploit such molecules to escape immune surveillance. Accumulating data support that their functions are dysregulated in lymphoid neoplasms, including plasma cell myeloma, myelodysplastic syndrome, and acute myeloid leukemia. In lymphoid neoplasms, aberrations in 9p24.1 (PD-L1, PD-L2, and JAK2 locus), latent Epstein-Barr virus infection, PD-L1 3'-untranslated region disruption, and constitutive JAK-STAT pathway are known mechanisms to induce PD-L1 expression in lymphoma cells. Clinical trials demonstrated that PD-1 blockade is an attractive way to restore host's immune function in hematological malignancies, particularly classical Hodgkin lymphoma. Numerous clinical trials exploring PD-1 blockade as a single therapy or in combination with other immune checkpoint inhibitors in patients with hematologic cancers are under way. Although impressive clinical response is observed with immune checkpoint inhibitors in patients with certain cancers, not all patients respond to immune checkpoint inhibitors. Therefore, to identify best candidates who would have excellent response to checkpoint inhibitors is of utmost importance. Several possible biomarkers are available, but consensus has not been made and pursuit to discover the best biomarker is ongoing.

  11. Non-volatile memory for checkpoint storage

    Science.gov (United States)

    Blumrich, Matthias A.; Chen, Dong; Cipolla, Thomas M.; Coteus, Paul W.; Gara, Alan; Heidelberger, Philip; Jeanson, Mark J.; Kopcsay, Gerard V.; Ohmacht, Martin; Takken, Todd E.

    2014-07-22

    A system, method and computer program product for supporting system initiated checkpoints in high performance parallel computing systems and storing of checkpoint data to a non-volatile memory storage device. 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. In one embodiment, the non-volatile memory is a pluggable flash memory card.

  12. 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.

  13. 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.

  14. 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 (<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.

  15. DNA damage checkpoint recovery and cancer development

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Haiyong [First affiliated hospital, Zhejiang University, School of medicine, Cancer Center, 79 Qingchun Road, Hangzhou 310003 (China); Zhang, Xiaoshan [Department of Genetics, University of Texas M.D. Anderson Cancer Center, Department of Genetics Unit 1010, 1515 Holcombe Blvd. Houston, TX 77030 (United States); Teng, Lisong, E-mail: lsteng@zju.edu.cn [First affiliated hospital, Zhejiang University, School of medicine, Cancer Center, 79 Qingchun Road, Hangzhou 310003 (China); Legerski, Randy J., E-mail: rlegersk@mdanderson.org [Department of Genetics, University of Texas M.D. Anderson Cancer Center, Department of Genetics Unit 1010, 1515 Holcombe Blvd. Houston, TX 77030 (United States)

    2015-06-10

    Cell cycle checkpoints were initially presumed to function as a regulator of cell cycle machinery in response to different genotoxic stresses, and later found to play an important role in the process of tumorigenesis by acting as a guard against DNA over-replication. As a counterpart of checkpoint activation, the checkpoint recovery machinery is working in opposition, aiming to reverse the checkpoint activation and resume the normal cell cycle. The DNA damage response (DDR) and oncogene induced senescence (OIS) are frequently found in precancerous lesions, and believed to constitute a barrier to tumorigenesis, however, the DDR and OIS have been observed to be diminished in advanced cancers of most tissue origins. These findings suggest that when progressing from pre-neoplastic lesions to cancer, DNA damage checkpoint barriers are overridden. How the DDR checkpoint is bypassed in this process remains largely unknown. Activated cytokine and growth factor-signaling pathways were very recently shown to suppress the DDR and to promote uncontrolled cell proliferation in the context of oncovirus infection. In recent decades, data from cell line and tumor models showed that a group of checkpoint recovery proteins function in promoting tumor progression; data from patient samples also showed overexpression of checkpoint recovery proteins in human cancer tissues and a correlation with patients' poor prognosis. In this review, the known cell cycle checkpoint recovery proteins and their roles in DNA damage checkpoint recovery are reviewed, as well as their implications in cancer development. This review also provides insight into the mechanism by which the DDR suppresses oncogene-driven tumorigenesis and tumor progression. - Highlights: • DNA damage checkpoint works as a barrier to cancer initiation. • DDR machinary response to genotoxic and oncogenic stress in similar way. • Checkpoint recovery pathways provide active signaling in cell cycle control. • Checkpoint

  16. How Do Changes to the Railroad Causeway in Utah's Great Salt Lake Affect Water and Salt Flow?

    Directory of Open Access Journals (Sweden)

    James S White

    Full Text Available Managing terminal lake elevation and salinity are emerging problems worldwide. We contribute to terminal lake management research by quantitatively assessing water and salt flow for Utah's Great Salt Lake. In 1959, Union Pacific Railroad constructed a rock-filled causeway across the Great Salt Lake, separating the lake into a north and south arm. Flow between the two arms was limited to two 4.6 meter wide rectangular culverts installed during construction, an 88 meter opening (referred to locally as a breach installed in 1984, and the semi porous material of the causeway. A salinity gradient developed between the two arms of the lake over time because the south arm receives approximately 95% of the incoming streamflow entering Great Salt Lake. The north arm is often at, or near, salinity saturation, averaging 317 g/L since 1966, while the south is considerably less saline, averaging 142 g/L since 1966. Ecological and industrial uses of the lake are dependent on long-term salinity remaining within physiological and economic thresholds, although optimal salinity varies for the ecosystem and between diverse stakeholders. In 2013, Union Pacific Railroad closed causeway culverts amid structural safety concerns and proposed to replace them with a bridge, offering four different bridge designs. As of summer 2015, no bridge design has been decided upon. We investigated the effect that each of the proposed bridge designs would have on north and south arm Great Salt Lake elevation and salinity by updating and applying US Geological Survey's Great Salt Lake Fortran Model. Overall, we found that salinity is sensitive to bridge size and depth, with larger designs increasing salinity in the south arm and decreasing salinity in the north arm. This research illustrates that flow modifications within terminal lakes cannot be separated from lake salinity, ecology, management, and economic uses.

  17. Water and salt balance of Great Salt Lake, Utah, and simulation of water and salt movement through the causeway

    Science.gov (United States)

    Wold, Steven R.; Thomas, Blakemore E.; Waddell, Kidd M.

    1997-01-01

    The water and salt balance of Great Salt Lake primarily depends on the amount of inflow from tributary streams and the conveyance properties of a causeway constructed during 1957-59 that divides the lake into the south and north parts. The conveyance properties of the causeway originally included two culverts, each 15 feet wide, and the permeable rock-fill material.During 1980-86, the salt balance changed as a result of record high inflow that averaged 4,627,000 acre-feet annually and modifications made to the conveyance properties of the causeway that included opening a 300-foot-wide breach. In this study, a model developed in 1973 by Waddell and Bolke to simulate the water and salt balance of the lake was revised to accommodate the high water-surface altitude and modifications made to the causeway. This study, done by the U.S. Geological Survey in cooperation with the Utah Department of Natural Resources, Division of State Lands and Forestry, updates the model with monitoring data collected during 1980-86. This report describes the calibration of the model and presents the results of simulations for three hypothetical 10-year periods.During January 1, 1980, to July 31, 1984, a net load of 0.5 billion tons of dissolved salt flowed from the south to the north part of the lake primarily as a result of record inflows. From August 1, 1984, when the breach was opened, to December 31,1986, a net load of 0.3 billion tons of dissolved salt flowed from the north to the south part of the lake primarily as a result of the breach.For simulated inflow rates during a hypothetical 10-year period resulting in the water-surface altitude decreasing from about 4,200 to 4,192 feet, there was a net movement of about 1.0 billion tons of dissolved salt from the south to the north part, and about 1.7 billion tons of salt precipitated in the north part. For simulated inflow rates during a hypothetical 10-year period resulting in a rise in water-surface altitude from about 4,200 to 4

  18. 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....

  19. 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...... the dilemma of genericness versus performance, we use automatic program specialization to transform the generic checkpointing methods into highly optimized ones. Specialization exploits two kinds of information: (i) structural properties about the program classes, (ii) knowledge of unmodified data structures...... in specific program phases. The latter information allows us to generate phase-specific checkpointing methods. We evaluate our approach on two benchmarks, a realistic application which consists of a program analysis engine, and a synthetic program which can serve as a metric. Specialization gives a speedup...

  20. Checkpoint triggering in a computer system

    Science.gov (United States)

    Cher, Chen-Yong

    2016-09-06

    According to an aspect, a method for triggering creation of a checkpoint in a computer system includes executing a task in a processing node of the computer system and determining whether it is time to read a monitor associated with a metric of the task. The monitor is read to determine a value of the metric based on determining that it is time to read the monitor. A threshold for triggering creation of the checkpoint is determined based on the value of the metric. Based on determining that the value of the metric has crossed the threshold, the checkpoint including state data of the task is created to enable restarting execution of the task upon a restart operation.

  1. 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.

  2. 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...

  3. 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…

  4. Selection of checkpoints provided by the ergonomic checkpoints in agriculture tool for mechanized sugarcane harvesting

    Directory of Open Access Journals (Sweden)

    Ana Lucy Rodrigues Ferreira

    2014-11-01

    Full Text Available The changing work dynamics of sugarcane harvesting owing to increasing mechanization has submitted workers to new working conditions, including interaction with machinery and equipment, thereby changing the profile of work-related diseases and injuries. One of the ways to solve problems resulting from the impact of mechanization on working conditions is the use of instruments that allow risk identification from man-labor ratio. This study aimed at selecting checkpoints applicable to mechanized sugarcane harvesting provided by the Ergonomic Checkpoints in Agriculture tool. A literature review of the mechanical sugarcane harvesting stages was conducted and, in light of its particularities, checkpoints provided by the aforementioned tool were analyzed. As a result, there were identified thirty-four checkpoints with potential application to mechanical sugarcane harvesting.

  5. 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

  6. Checkpoint Inhibitors Hold Promise for Rare Melanoma

    Science.gov (United States)

    Patients with a rare form of melanoma, called desmoplastic melanoma, may be particularly likely to benefit from immune checkpoint inhibitors, a new study shows. As this Cancer Currents post explains, an NCI-sponsored clinical trial is already testing one such drug, pembrolizumab (Keytruda) in patients with this cancer.

  7. Regulation of mitotic progression by the spindle assembly checkpoint

    DEFF Research Database (Denmark)

    Lischetti, Tiziana; Nilsson, Jakob

    2015-01-01

    Equal segregation of sister chromatids during mitosis requires that pairs of kinetochores establish proper attachment to microtubules emanating from opposite poles of the mitotic spindle. The spindle assembly checkpoint (SAC) protects against errors in segregation by delaying sister separation...... in response to improper kinetochore-microtubule interactions, and certain checkpoint proteins help to establish proper attachments. Anaphase entry is inhibited by the checkpoint through assembly of the mitotic checkpoint complex (MCC) composed of the 2 checkpoint proteins, Mad2 and BubR1, bound to Cdc20...

  8. Immigrants and Immigration in Israeli Children's Literature.

    Science.gov (United States)

    Yitzhaki, Moshe; Richter, Nava

    Millions of people have immigrated to Israel throughout the 1900s and before. Immigration waves are considered the most important social, political, and economical turning points in the history of Israel. This study analyzes the content of Israeli children's books dealing with immigrants and immigration to determine the image of immigrants and…

  9. Compiler-Enhanced Incremental Checkpointing for OpenMP Applications

    Energy Technology Data Exchange (ETDEWEB)

    Bronevetsky, G; Marques, D; Pingali, K; Rugina, R; McKee, S A

    2008-01-21

    As modern supercomputing systems reach the peta-flop performance range, they grow in both size and complexity. This makes them increasingly vulnerable to failures from a variety of causes. Checkpointing is a popular technique for tolerating such failures, enabling applications to periodically save their state and restart computation after a failure. Although a variety of automated system-level checkpointing solutions are currently available to HPC users, manual application-level checkpointing remains more popular due to its superior performance. This paper improves performance of automated checkpointing via a compiler analysis for incremental checkpointing. This analysis, which works with both sequential and OpenMP applications, reduces checkpoint sizes by as much as 80% and enables asynchronous checkpointing.

  10. 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.

  11. Cell cycle checkpoints: methods and protocols

    Directory of Open Access Journals (Sweden)

    Carlo Alberto Redi

    2012-09-01

    Full Text Available As it is well known at the end of each cell cycle step there are checkpoints to verify that DNA duplication and segregation (among other events met every requirements before the cell is allowed to proceed to the next step. Multiple signaling molecules, notably cyclins and the cyclin-dependent kinases (CDKs, play major roles in the cell cycle checkpoint’s control....

  12. Mechanisms of resistance to immune checkpoint inhibitors.

    Science.gov (United States)

    Jenkins, Russell W; Barbie, David A; Flaherty, Keith T

    2018-01-01

    Immune checkpoint inhibitors (ICI) targeting CTLA-4 and the PD-1/PD-L1 axis have shown unprecedented clinical activity in several types of cancer and are rapidly transforming the practice of medical oncology. Whereas cytotoxic chemotherapy and small molecule inhibitors ('targeted therapies') largely act on cancer cells directly, immune checkpoint inhibitors reinvigorate anti-tumour immune responses by disrupting co-inhibitory T-cell signalling. While resistance routinely develops in patients treated with conventional cancer therapies and targeted therapies, durable responses suggestive of long-lasting immunologic memory are commonly seen in large subsets of patients treated with ICI. However, initial response appears to be a binary event, with most non-responders to single-agent ICI therapy progressing at a rate consistent with the natural history of disease. In addition, late relapses are now emerging with longer follow-up of clinical trial populations, suggesting the emergence of acquired resistance. As robust biomarkers to predict clinical response and/or resistance remain elusive, the mechanisms underlying innate (primary) and acquired (secondary) resistance are largely inferred from pre-clinical studies and correlative clinical data. Improved understanding of molecular and immunologic mechanisms of ICI response (and resistance) may not only identify novel predictive and/or prognostic biomarkers, but also ultimately guide optimal combination/sequencing of ICI therapy in the clinic. Here we review the emerging clinical and pre-clinical data identifying novel mechanisms of innate and acquired resistance to immune checkpoint inhibition.

  13. Reverse engineering of the spindle assembly checkpoint.

    Directory of Open Access Journals (Sweden)

    Andreas Doncic

    Full Text Available The Spindle Assembly Checkpoint (SAC is an intracellular mechanism that ensures proper chromosome segregation. By inhibiting Cdc20, a co-factor of the Anaphase Promoting Complex (APC, the checkpoint arrests the cell cycle until all chromosomes are properly attached to the mitotic spindle. Inhibition of Cdc20 is mediated by a conserved network of interacting proteins. The individual functions of these proteins are well characterized, but understanding of their integrated function is still rudimentary. We here describe our attempts to reverse-engineer the SAC network based on gene deletion phenotypes. We begun by formulating a general model of the SAC which enables us to predict the rate of chromosomal missegregation for any putative set of interactions between the SAC proteins. Next the missegregation rates of seven yeast strains are measured in response to the deletion of one or two checkpoint proteins. Finally, we searched for the set of interactions that correctly predicted the observed missegregation rates of all deletion mutants. Remarkably, although based on only seven phenotypes, the consistent network we obtained successfully reproduces many of the known properties of the SAC. Further insights provided by our analysis are discussed.

  14. Targeting Immune Cell Checkpoints during Sepsis

    Directory of Open Access Journals (Sweden)

    Naeem K. Patil

    2017-11-01

    Full Text Available Immunosuppression is increasingly being recognized as one of the causes of increased morbidity and mortality during sepsis. Both innate and adaptive immune system dysfunction have been shown to cause an impaired ability to eradicate the primary infection and also lead to frequent occurrence of secondary opportunistic infections. Pre-clinical and clinical studies have shown that inhibitory immune checkpoint molecules, including programmed death-1 (PD-1, programmed death ligand-1 (PD-L1, cytotoxic T lymphocyte antigen-4 (CTLA-4, T cell membrane protein-3 (TIM-3, Lymphocyte activation-gene-3 (LAG-3 and 2B4, are upregulated during the course of sepsis. Engagement of these inhibitory molecules on various immune cells has been consistently shown to inhibit innate immune cell functions (e.g., phagocytosis, cytokine production and pathogen clearance and also lead to impaired T cell competence. In numerous pre-clinical models of sepsis, therapeutic agents aimed at blocking engagement of inhibitory immune checkpoints on immune cells have been shown to improve innate and adaptive immune cell functions, increase host resistance to infection and significantly improve survival. Therefore, immunotherapy with immune cell checkpoint inhibitors holds significant potential for the future of sepsis therapy and merits further investigation.

  15. Checkpoint Blockade in Lung Cancer and Mesothelioma.

    Science.gov (United States)

    Lievense, Lysanne A; Sterman, Daniel H; Cornelissen, Robin; Aerts, Joachim G

    2017-08-01

    In the last decade, immunotherapy has emerged as a new treatment modality in cancer. The most success has been achieved with the class of checkpoint inhibitors (CPIs), antibodies that unleash the antitumor immune response. After the success in melanoma, numerous clinical trials are being conducted investigating CPIs in lung cancer and mesothelioma. The programmed death protein (PD) 1-PD ligand 1/2 pathway and cytotoxic T lymphocyte-associated protein 4 are currently the most studied immunotherapeutic targets in these malignancies. In non-small cell lung cancer, anti-PD-1 antibodies have become part of the approved treatment arsenal. In small cell lung cancer and mesothelioma, the efficacy of checkpoint inhibition has not yet been proven. In this Concise Clinical Review, an overview of the landmark clinical trials investigating checkpoint blockade in lung cancer and mesothelioma is provided. Because response rates are around 20% in the majority of clinical trials, there is much room for improvement. Predictive biomarkers are therefore essential to fully develop the potential of CPIs. To increase efficacy, multiple clinical trials investigating the combination of cytotoxic T lymphocyte-associated protein 4 inhibitors and PD-1/PD ligand 1 blockade in lung cancer and mesothelioma are being conducted. Given the potential benefit of immunotherapy, implementation of current and new knowledge in trial designs and interpretation of results is essential for moving forward.

  16. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  18. 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...

  19. 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...

  20. A survey of checkpointing algorithms for parallel and distributed ...

    Indian Academy of Sciences (India)

    the cost of information loss due to failure is small and the overhead due to checkpointing is not significant. ... and information loss is not permitted, a checkpoint may be taken after every transaction, increasing the ... The processors communicate with each other by exchanging messages through communication channels.

  1. Eukaryotic checkpoints are absent in the cell division cycle of ...

    Indian Academy of Sciences (India)

    Unknown

    checkpoints' which are known to regulate the eukaryotic cell cycle may be absent or altered in. E. histolytica. [Banerjee S, Das S and Lohia A 2002 Eukaryotic checkpoints are absent in the cell division cycle of Entamoeba histolytica; J. Biosci. (Suppl.

  2. 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.

  3. 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.

  4. Data collection and development of a hydrodynamic and temperature model to evaluate causeway modifications at the mouth of the Yakima River

    Science.gov (United States)

    Martinez Baquero, G. F.; Furnans, J.; Hudson, C.; Magan, C.

    2012-12-01

    Management decisions on rivers and associated habitats require sound tools to identify major drivers for spatial and temporal variations of temperature and related water quality variables. 3D hydrodynamic and water quality models are key components to abstract flow dynamics in complex river systems as they allow extrapolating available observations to ungaged locations and alternative scenarios. The data collection and model development are intended to support the Mid-Columbia Fisheries Enhancement Group in conjunction with the Benton Conservation District in efforts to understand how seasonal flow patterns in the Yakima and Columbia rivers interact with the Yakima delta geometry to cause the relatively high water temperatures previously observed west of Bateman Island. These high temperatures are suspected of limiting salmonid success in the area, possibly contributing to adjustments in migration patterns and increased predation. The Environmental Fluid Dynamics Code (EFDC) and Water Quality Analysis Simulation Program (WASP) are used to model flow patterns and enable simulations of temperature distributions and water quality parameters at the confluence. Model development is supported by a bathymetric campaign in 2011 to evaluate delta geometry and to construct the EFDC domain, a sonar river survey in 2012 to measure velocity profiles and to enable model calibration, and a continuous collection of temperature and dissolved oxygen records from Level Scout probes at key locations during last year to drive water quality simulations. The current model is able to reproduce main flow features observed at the confluence and is being prepared to integrate previous and current temperature observations. The final model is expected to evaluate scenarios for the removal or alteration of the Bateman Island Causeway. Alterations to the causeway that permit water passage to the south of Bateman Island are likely to dramatically alter the water flow patterns through the Yakima

  5. Demands of immigration among Chinese immigrant nurses.

    Science.gov (United States)

    Ma, Amy X; Griffin, Mary T Quinn; Capitulo, Katie L; Fitzpatrick, Joyce J

    2010-10-01

    The purpose of this study was to identify the demands of immigration among Chinese nurses that have immigrated to the USA. The relationship between the demands of immigration and length of stay in the USA was investigated also. A descriptive correlational study design was used. A convenience sample of 128 nurses was recruited. A self-administered survey was conducted using the demands of immigration scale developed by Aroian, along with a demographic questionnaire. The results showed Chinese immigrant nurses have high demands of immigration. There were significant negative relationships between the demands of immigration and length of stay in the USA. Immigration demands decreased as length of stay increased but remained high even for those who had been in the USA for > 5 years. This information is vital to health-care agencies designing and implementing adaptation programmes targeting these demands to facilitate Chinese nurses' adaptation process. © 2010 Blackwell Publishing Asia Pty Ltd.

  6. 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.

  7. DNA damage checkpoint and repair centers

    DEFF Research Database (Denmark)

    Lisby, Michael; Rothstein, Rodney

    2004-01-01

    recognition and binding of DNA ends by the Mre11 complex and Ku70/80; second, end-processing and binding of single-stranded DNA by replication protein A, which recruits checkpoint proteins; third, recombinational repair during S and G(2) phase; and fourth, disassembly of foci and resumption of the cell cycle.......In eukaryotes, recombinational repair is choreographed by multiprotein complexes that are organized into focal assemblies. These foci are highly dynamic giga-dalton structures capable of simultaneously repairing multiple DNA lesions. Moreover, the composition of these repair centers depends...... on the nature of the DNA lesion and is tightly coordinated with progression of the cell cycle. Components of DNA repair centers are regulated by post-translational modifications such as phosphorylation, ubiquitination and sumoylation. Repair foci progress through four distinct stages: first, DNA damage...

  8. 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.

  9. 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.

  10. 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…

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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...

  16. The Ideal Immigrant

    Science.gov (United States)

    Delgadillo, Theresa

    2011-01-01

    The public discourse about immigration in the United States has long been fraught with xenophobia and racism. Since 9/11, moreover, the immigration issue has been firmly linked to questions of national security in the public imagination. In this recent period, the state has asserted extraordinary controls over immigrants and citizens that affect…

  17. Chloroplast division checkpoint in eukaryotic algae

    Science.gov (United States)

    Sumiya, Nobuko; Fujiwara, Takayuki; Era, Atsuko; Miyagishima, Shin-ya

    2016-01-01

    Chloroplasts evolved from a cyanobacterial endosymbiont. It is believed that the synchronization of endosymbiotic and host cell division, as is commonly seen in existing algae, was a critical step in establishing the permanent organelle. Algal cells typically contain one or only a small number of chloroplasts that divide once per host cell cycle. This division is based partly on the S-phase–specific expression of nucleus-encoded proteins that constitute the chloroplast-division machinery. In this study, using the red alga Cyanidioschyzon merolae, we show that cell-cycle progression is arrested at the prophase when chloroplast division is blocked before the formation of the chloroplast-division machinery by the overexpression of Filamenting temperature-sensitive (Fts) Z2-1 (Fts72-1), but the cell cycle progresses when chloroplast division is blocked during division-site constriction by the overexpression of either FtsZ2-1 or a dominant-negative form of dynamin-related protein 5B (DRP5B). In the cells arrested in the prophase, the increase in the cyclin B level and the migration of cyclin-dependent kinase B (CDKB) were blocked. These results suggest that chloroplast division restricts host cell-cycle progression so that the cell cycle progresses to the metaphase only when chloroplast division has commenced. Thus, chloroplast division and host cell-cycle progression are synchronized by an interactive restriction that takes place between the nucleus and the chloroplast. In addition, we observed a similar pattern of cell-cycle arrest upon the blockage of chloroplast division in the glaucophyte alga Cyanophora paradoxa, raising the possibility that the chloroplast division checkpoint contributed to the establishment of the permanent organelle. PMID:27837024

  18. 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

  19. Immune checkpoint inhibitors and prostate cancer: a new frontier?

    Directory of Open Access Journals (Sweden)

    Alessandra Modena

    2016-04-01

    Full Text Available Despite recent advances in the treatment of metastatic castrationresistant prostate cancer (mCRPC, agents that provide durable disease control and long-term survival are still needed. It is a fact that a tumor-induced immunosuppressive status (mediated by aberrant activation of inhibitory immune checkpoint pathways as a mechanism to evade host immune surveillance plays a crucial role in the pathogenesis of cancer, including prostate cancer (PC, making CRPC patients suitable candidates for immunotherapy. Therefore, growing interest of anticancer research aims at blocking immune checkpoints (mainly targeting CTLA-4 and PD1/PD-L1 pathways to restore and enhance cellular-mediated antitumor immunity and achieve durable tumor regression. In this review, we describe the current knowledge regarding the role of immune checkpoints in mediating PC progression, focusing on CTLA-4 and PD1 pathways. We also provide current clinical data available, an update on ongoing trials of immune checkpoint inhibitors in PC. Finally, we discuss the necessity to identify prognostic and predictive biomarkers of immune activity, and we analyze new immune checkpoints with a role as promising targets for PC therapy.

  20. 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....

  1. Immigration and Prosecutorial Discretion.

    Science.gov (United States)

    Apollonio, Dorie; Lochner, Todd; Heddens, Myriah

    Immigration has become an increasingly salient national issue in the US, and the Department of Justice recently increased federal efforts to prosecute immigration offenses. This shift, however, relies on the cooperation of US attorneys and their assistants. Traditionally federal prosecutors have enjoyed enormous discretion and have been responsive to local concerns. To consider how the centralized goal of immigration enforcement may have influenced federal prosecutors in regional offices, we review their prosecution of immigration offenses in California using over a decade's worth of data. Our findings suggest that although centralizing forces influence immigration prosecutions, individual US attorneys' offices retain distinct characteristics. Local factors influence federal prosecutors' behavior in different ways depending on the office. Contrary to expectations, unemployment rates did not affect prosecutors' willingness to pursue immigration offenses, nor did local popular opinion about illegal immigration.

  2. America's immigration "problem.".

    Science.gov (United States)

    Sassen, S

    1989-01-01

    Immigration has traditionally aroused strong passions in the US. Though Americans profess pride in their history as a nation of immigrants, each new wave of immigrants is met with strenuous opposition. Sassen points out that this opposition underestimates the US's capacity to absorb more people and fails to appreciate the political and economic forces that give rise to immigration. The outcry over rising illegal immigration culminated in the 1986 Immigration Reform and Control Act. So far, the law's effectiveness has been limited. 1.8 million immigrants applied to regularize their status. However, there is growing evidence that the employer sanctions program is resulting in discrimination against minority workers who are US citizens, and in various abuses against undocumented workers. Meanwhile, illegal immigration continues to rise. The 1986 law, like earlier laws, is based o a faulty understanding of immigration causes. The US played a crucial role in the 1960s and 1970s in developing today's global economic system. This system contributed to the creation of pools of potential immigrants and to the formation of links between the industrialized and developing countries. In sum, foreign investment and promotion of export-oriented growth i the US in developing countries has served to increase immigration to the US. A workable US immigration policy would be based o the recognition that the US bears a certain amount of responsibility for international labor migrations. The precise features of a fair immigration policy will have to be elaborated. However, it is clear that US immigration policy will continue to be counterproductive as long as it places the responsibility for the formation of international migrations exclusively upon the migrants themselves.

  3. 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

  4. 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...

  5. Checkpoint Inhibitors and Their Application in Breast Cancer

    Science.gov (United States)

    Bedognetti, Davide; Maccalli, Cristina; Bader, Salha B.J. Al; Marincola, Francesco M.; Seliger, Barbara

    2016-01-01

    Summary Immune checkpoints are crucial for the maintenance of self-tolerance and for the modulation of immune responses in order to minimize tissue damage. Tumor cells take advantage of these mechanisms to evade immune recognition. A significant proportion of tumors, including breast cancers, can express co-inhibitory molecules that are important formediating the escape from T cell-mediated immune surveillance. The interaction of inhibitory receptors with their ligands can be blocked by specific molecules. Monoclonal antibodies (mAbs) directed against the cytotoxic T lymphocyte-associated antigen-4 (CTLA4) and, more recently, against the programmed cell death protein 1 (PD1), have been approved for the therapy of melanoma (anti-CTLA4 and anti-PD1 mAbs) and non-small cell lung cancer (anti-PD1 mAbs). Moreover, inhibition of PD1 signaling has shown extremely promising signs of activity in breast cancer. An increasing number of molecules directed against other immune checkpoints are currently under clinical development. In this review, we summarize the evidence supporting the implementation of checkpoint inhibition in breast cancer by reviewing in detail data on PD-L1 expression and its regulation. In addition, opportunities to boost anti-tumor immunity in breast cancer with checkpoint inhibitor-based immunotherapies alone and in combination with other treatment options will be discussed. PMID:27239172

  6. A survey of checkpointing algorithms for parallel and distributed ...

    Indian Academy of Sciences (India)

    Checkpointing for sharedmemory systems primarily extend cache coherence protocolstomaintain a consistent memory. All of them assume that the main memory is safe for storing the context. Recently algorithms have been published for distributed shared memory systems, which extend the cache coherence protocols used ...

  7. 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

  8. 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.

  9. Immune-Checkpoint Blockade and Active Immunotherapy for Glioma

    Directory of Open Access Journals (Sweden)

    Brian J. Ahn

    2013-11-01

    Full Text Available 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.

  10. 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.

  11. The spindle assembly checkpoint: progress and persistent puzzles.

    Science.gov (United States)

    Hauf, Silke

    2013-12-01

    The spindle assembly checkpoint is a conserved mitotic signalling pathway that ensures the equal segregation of chromosomes to daughter cells. Despite intensive work in many model organisms, key features of this safety mechanism remain unexplained. In the present review, I briefly summarize advances made in the last few years, and then focus on unexplored corners of this signalling pathway.

  12. 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

    stage III MMel patients after adjuvant ipilimumab + nivolumab (but not nivolumab alone). These biomarkers should be validated in prospective trials in MMel.The clinical management of metastatic melanoma requires predictors of the response to checkpoint blockade. Here, the authors use immunological...

  13. Targeting immune checkpoints: New opportunity for mesothelioma treatment?

    Science.gov (United States)

    Marcq, Elly; Pauwels, Patrick; van Meerbeeck, Jan P; Smits, Evelien L J

    2015-12-01

    Malignant pleural mesothelioma is an aggressive cancer linked to asbestos exposure in most patients. Due to the long latency between exposure and presentation, incidence is expected to further increase in the next decade, despite the ban on asbestos import which occurred at the end of last century in industrialized countries. Platinum-based palliative chemotherapy is the only treatment with proven benefit on outcome, resulting in selected patients in a median overall survival of about 1 year. Therefore, there is room for therapeutic improvement using a new strategy to prolong survival. Dealing with cancer cell induced immunosuppression is a promising approach. Reactivating immune responses that are silenced by immune checkpoints recently gained a lot of interest. Checkpoint blockade has already shown promising preclinical and clinical results in several cancer types and is currently also being investigated in mesothelioma. Here, we discuss the expression patterns and mechanisms of action of CTLA-4 and PD-1 as the two most studied and of TIM-3 and LAG-3 as two interesting upcoming immune checkpoints. Furthermore, we review the clinical results of molecules blocking these immune checkpoints and point out their future opportunities with a special focus on mesothelioma. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. 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

  15. The absence of a DNA replication checkpoint in porcine zygotes

    Czech Academy of Sciences Publication Activity Database

    Vacková, I.; Křen, Radomír; Loi, P.; Krylov, V.; Fulka Jr., J.

    2006-01-01

    Roč. 14, 1 (2006), s. 33-37 ISSN 0967-1994 Institutional research plan: CEZ:AV0Z50450515 Keywords : checkpoint * DNA replication * fertilization Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 0.782, year: 2006

  16. Harnessing the Power of Onco-Immunotherapy with Checkpoint Inhibitors

    Directory of Open Access Journals (Sweden)

    Karishma R. Rajani

    2015-11-01

    Full Text Available Oncolytic viruses represent a diverse class of replication competent viruses that curtail tumor growth. These viruses, through their natural ability or through genetic modifications, can selectively replicate within tumor cells and induce cell death while leaving normal cells intact. Apart from the direct oncolytic activity, these viruses mediate tumor cell death via the induction of innate and adaptive immune responses. The field of oncolytic viruses has seen substantial advancement with the progression of numerous oncolytic viruses in various phases of clinical trials. Tumors employ a plethora of mechanisms to establish growth and subsequently metastasize. These include evasion of immune surveillance by inducing up-regulation of checkpoint proteins which function to abrogate T cell effector functions. Currently, antibodies blocking checkpoint proteins such as anti-cytotoxic T-lymphocyte antigen-4 (CTLA-4 and anti-programmed cell death-1 (PD-1 have been approved to treat cancer and shown to impart durable clinical responses. These antibodies typically need pre-existing active immune tumor microenvironment to establish durable clinical outcomes and not every patient responds to these therapies. This review provides an overview of published pre-clinical studies demonstrating superior therapeutic efficacy of combining oncolytic viruses with checkpoint blockade compared to monotherapies. These studies provide compelling evidence that oncolytic therapy can be potentiated by coupling it with checkpoint therapies.

  17. 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;

  18. Synaptonemal Complex Components Are Required for Meiotic Checkpoint Function in Caenorhabditis elegans

    Science.gov (United States)

    Bohr, Tisha; Ashley, Guinevere; Eggleston, Evan; Firestone, Kyra; Bhalla, Needhi

    2016-01-01

    Synapsis involves the assembly of a proteinaceous structure, the synaptonemal complex (SC), between paired homologous chromosomes, and is essential for proper meiotic chromosome segregation. In Caenorhabditis elegans, the synapsis checkpoint selectively removes nuclei with unsynapsed chromosomes by inducing apoptosis. This checkpoint depends on pairing centers (PCs), cis-acting sites that promote pairing and synapsis. We have hypothesized that the stability of homolog pairing at PCs is monitored by this checkpoint. Here, we report that SC components SYP-3, HTP-3, HIM-3, and HTP-1 are required for a functional synapsis checkpoint. Mutation of these components does not abolish PC function, demonstrating they are bona fide checkpoint components. Further, we identify mutant backgrounds in which the instability of homolog pairing at PCs does not correlate with the synapsis checkpoint response. Altogether, these data suggest that, in addition to homolog pairing, SC assembly may be monitored by the synapsis checkpoint. PMID:27605049

  19. 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...

  20. 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…

  1. Irelands' Immigrant Children

    Science.gov (United States)

    Culleton, Jonathan

    2004-01-01

    In industrialised Western nations generally, and European Union (EU) nations particularly, immigration is an issue of considerable concern and debate. In the EU, however, discussion of immigration has tended to centre on a number of policy issues, from reliance on welfare provision, to labour force participation, to healthcare provision, to…

  2. Educating Recent Immigrants.

    Science.gov (United States)

    IDRA Newsletter, 1994

    1994-01-01

    This newsletter contains six articles all related to the theme of education for recent legal and illegal immigrants. In "Golden Lord with Us from the Main Forest: Some Thoughts on the Education of Recent Immigrants," Aurelio M. Montemayor reflects on his experiences growing up in a bilingual, bicultural extended family of…

  3. 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

  4. 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

  5. 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

  6. Attitudes toward 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....

  7. 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....

  8. 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...

  9. [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

  10. 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.

  11. Voting over Selective Immigration Policies with Immigration Aversion

    OpenAIRE

    Giuseppe Russo

    2008-01-01

    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...

  12. 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…

  13. 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.…

  14. 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.

  15. 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....

  16. Complex Commingling: Nucleoporins and the Spindle Assembly Checkpoint

    Directory of Open Access Journals (Sweden)

    Ikram Mossaid

    2015-11-01

    Full Text Available The segregation of the chromosomes during mitosis is an important process, in which the replicated DNA content is properly allocated into two daughter cells. To ensure their genomic integrity, cells present an essential surveillance mechanism known as the spindle assembly checkpoint (SAC, which monitors the bipolar attachment of the mitotic spindle to chromosomes to prevent errors that would result in chromosome mis-segregation and aneuploidy. Multiple components of the nuclear pore complex (NPC, a gigantic protein complex that forms a channel through the nuclear envelope to allow nucleocytoplasmic exchange of macromolecules, were shown to be critical for faithful cell division and implicated in the regulation of different steps of the mitotic process, including kinetochore and spindle assembly as well as the SAC. In this review, we will describe current knowledge about the interconnection between the NPC and the SAC in an evolutional perspective, which primarily relies on the two mitotic checkpoint regulators, Mad1 and Mad2. We will further discuss the role of NPC constituents, the nucleoporins, in kinetochore and spindle assembly and the formation of the mitotic checkpoint complex during mitosis and interphase.

  17. The cell cycle checkpoint inhibitors in the treatment of leukemias.

    Science.gov (United States)

    Ghelli Luserna di Rora', A; Iacobucci, I; Martinelli, G

    2017-03-29

    The inhibition of the DNA damage response (DDR) pathway in the treatment of cancers has recently reached an exciting stage with several cell cycle checkpoint inhibitors that are now being tested in several clinical trials in cancer patients. Although the great amount of pre-clinical and clinical data are from the solid tumor experience, only few studies have been done on leukemias using specific cell cycle checkpoint inhibitors. This review aims to summarize the most recent data found on the biological mechanisms of the response to DNA damages highlighting the role of the different elements of the DDR pathway in normal and cancer cells and focusing on the main genetic alteration or aberrant gene expression that has been found on acute and chronic leukemias. This review, for the first time, outlines the most important pre-clinical and clinical data available on the efficacy of cell cycle checkpoint inhibitors in single agent and in combination with different agents normally used for the treatment of acute and chronic leukemias.

  18. An Overview of Immune Checkpoint Inhibitors in Gynecologic Cancers.

    Science.gov (United States)

    Castellano, Tara; Moore, Kathleen N; Holman, Laura L

    2018-03-01

    The goal of this study was to compile a review of topics pertinent to the use of immune checkpoint inhibitors in gynecologic malignancies, including foundation for use, current agents available and trials in gynecologic cancers, special populations of interest, identification and management of toxicities, and considerations in predictive biomarkers and response assessment. A literature review of selected topics in reference to immune checkpoint inhibitors and gynecologic cancers was conducted on PubMed and the US Food and Drug Administration drug search application. A review of current and ongoing clinical trials was performed in clinicaltrials.gov, and selected preliminary results reported in PubMed abstracts and through the American Society of Clinical Oncologists were compiled. Although immunotherapy in gynecologic malignancy is relatively new, 7 agents are currently approved for use in other oncologic indications, and a multitude of trials in gynecologic cancer are ongoing. Immunotherapy has a specific set of drug toxicities that manifest and are managed unlike traditional cytotoxic therapies. Application of the knowledge of immune checkpoint inhibitor use in gynecologic cancers will improve care for women with cancers of the female reproductive tract. As more complex and newer immunotherapies evolve, it will be vital to accurately characterize each specific drug class and management thereof. Copyright © 2018 Elsevier HS Journals, Inc. All rights reserved.

  19. How integrated are immigrants?

    Directory of Open Access Journals (Sweden)

    Rickard Sandell

    2015-12-01

    Full Text Available Background: The successful integration of immigrants is seen as a principal means to secure economic growth and welfare in many countries. Success in this task depends on the capacity to formulate effective integration policies, which in turn is based on research capable of describing and explaining the integration process properly. Objective: Our objective is to define a conceptual and quantifiable measure of full immigrant integration.This enables a quantitative evaluation of how integrated immigrants are in a specific context in an immigrant - native system - a question poorly addressed by past research. Methods: Our approach consists of looking at the functional dependency of different integrationquantifiers on immigrant density. The empirical analysis uses register data from Spain. We focus on social integration and labour market integration in formal employment. Results: In our empirical analysis we find dramatic differences in immigrant integration levels across integration contexts. While labour market integration approaches the level of full integration, social integration quickly declines as immigration levels surge. It is shown that these differences are primarily due to the presence of social network effects in the social integration process, absent in the labour market integration process. Conclusions: Proper identification of integration deficits and its causes is likely to improve the efficiency of integration policy making, and the capacity to reach integration targets. Our framework has this quality. The research presented here shows that full labour market integration of immigrants is a realistic target. However, it also shows that, if left unattended, the segregation forces contained in social networks, quite dramatically obstruct the social integration process. Lack of social integration undermines the strategy of reliance on increasing immigration to secure future economic well-being that many governments andinternational

  20. 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.

  1. 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...

  2. 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...

  3. S&E immigration

    Science.gov (United States)

    Despite an overall decline in immigration to the United States in 1993, the number of scientists and engineers (S&Es) entering the country continued to rise, with women representing 21.3% of the total admitted with permanent resident status. According to the Immigration and Naturalization Service, 23,534 S&Es were admitted to the United States on permanent visas in 1993, 3.1% more than in 1992. Of that total, 5,020 were women. S&Es made up 2.6% of the total U.S. immigration in 1993. The slight 1993 increase followed a large jump in 1992 of 62% over the previous year.

  4. Immigration measures, 1988.

    Science.gov (United States)

    1988-01-01

    In 1988, the Government of Norway undertook the following immigration measures: 1) it merged the Office of Immigration, which deals with asylum matters, and the Government Refugee Agency, which handles reception and settlement, into a new Directorate for Immigration under the Ministry of Local Government and Labour; 2) it instituted visa requirements for Chileans; and 3) it established a new reception program, under which five regional reception centers are to be created accommodating 200 to 300 people each, where asylum seekers will be placed until they have completed their police interview and a municipality has agreed to accept them. full text

  5. 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.

  6. 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...

  7. 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...

  8. Immigration und Integration

    OpenAIRE

    Rauscher, Anton

    2003-01-01

    Immigration und Integration : eine Herausforderung für Kirche, Gesellschaft und Politik in Deutschland und den USA / hrsg. von Anton Rauscher. - Berlin : Duncker & Humblot, 2003. - 174 S. - (Soziale Orientierung ; 15)

  9. Encounters with immigrant customers

    DEFF Research Database (Denmark)

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

    2013-01-01

    OBJECTIVES: To explore the challenges that Danish community pharmacy staff encounter when serving non-Western immigrant customers. Special attention was paid to similarities and differences between the perceptions of pharmacists and pharmacy assistants. METHODS: A questionnaire was distributed...... to one pharmacist and one pharmacy assistant employed at each of the 55 community pharmacies located in the five local councils in Denmark with the highest number of immigrant inhabitants. KEY FINDINGS: The total response rate was 76% (84/110). Most respondents found that the needs of immigrant customers...... 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...

  10. Experiences with treating immigrants

    DEFF Research Database (Denmark)

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

    2012-01-01

    of human trafficking. Interviews were transcribed and analysed using thematic analysis. RESULTS: The interviews highlighted specific challenges to treating immigrants in mental health services across all 16 countries including complications with diagnosis, difficulty in developing trust and increased risk...

  11. 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...

  12. Immigrant Child Poverty

    DEFF Research Database (Denmark)

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

    2015-01-01

    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......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...

  13. "A Day Without Immigrants"

    DEFF Research Database (Denmark)

    Heiskanen, Benita

    2009-01-01

    , policy makers, and participants. Although much of these debates ostensibly centered around illegal Latino/a immigration to the United States, underneath the discussion ran a curious ideological thread, one that invoked groups' right to be in the United States in the first place. The article argues...... 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......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...

  14. Two-level incremental checkpoint recovery scheme for reducing system total overheads.

    Science.gov (United States)

    Li, Huixian; Pang, Liaojun; Wang, Zhangquan

    2014-01-01

    Long-running applications are often subject to failures. Once failures occur, it will lead to unacceptable system overheads. The checkpoint technology is used to reduce the losses in the event of a failure. For the two-level checkpoint recovery scheme used in the long-running tasks, it is unavoidable for the system to periodically transfer huge memory context to a remote stable storage. Therefore, the overheads of setting checkpoints and the re-computing time become a critical issue which directly impacts the system total overheads. Motivated by these concerns, this paper presents a new model by introducing i-checkpoints into the existing two-level checkpoint recovery scheme to deal with the more probable failures with the smaller cost and the faster speed. The proposed scheme is independent of the specific failure distribution type and can be applied to different failure distribution types. We respectively make analyses between the two-level incremental and two-level checkpoint recovery schemes with the Weibull distribution and exponential distribution, both of which fit with the actual failure distribution best. The comparison results show that the total overheads of setting checkpoints, the total re-computing time and the system total overheads in the two-level incremental checkpoint recovery scheme are all significantly smaller than those in the two-level checkpoint recovery scheme. At last, limitations of our study are discussed, and at the same time, open questions and possible future work are given.

  15. 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.

  16. Immigration and Politics

    OpenAIRE

    Cornelius, Wayne A.; Rosenblum, Marc R.

    2004-01-01

    With nearly one in ten residents of advanced industrialized states now an immigrant, international migration has become a fundamental driver of social, economic, and political change. We review alternative models of migratory behavior (which emphasize structural factors largely beyond states’ control) as well as models of immigration policy making that seek to explain the gaps between stated policy and actual outcomes. Some scholars attempt to explain the limited efficacy of control policies ...

  17. 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 ...

  18. Myasthenia gravis: An emerging toxicity of immune checkpoint inhibitors.

    Science.gov (United States)

    Makarious, D; Horwood, K; Coward, J I G

    2017-09-01

    The advent of immunotherapy has heralded a number of significant advances in the treatment of particular malignancies associated with poor prognosis (melanoma, non-small-cell lung, renal and head/neck cancers). The success witnessed with therapeutic agents targeting cytotoxic T-lymphocyte-associated protein 4, programmed cell death protein 1 and programmed cell death ligand 1 immune checkpoints has inevitably led to an explosion in their clinical application and the subsequent recognition of specific toxicity profiles distinct from those long recognised with chemotherapy. Consequently, as the utility of such therapies broaden, understanding the nature, timing and management of these immune-related adverse events (irAEs) becomes increasingly significant. Although neurological irAEs are considered relatively rare in comparison with hepatitis, colitis, pneumonitis and endocrinopathies, one emerging side-effect is myasthenia gravis (MG). Among the 23 reported cases of immune checkpoint inhibitor-associated MG, 72.7% were de novo presentations, 18.2% were exacerbations of pre-existing MG and 9.1% were exacerbations of subclinical MG. The average onset of symptoms was within 6 weeks (range 2-12 weeks) of treatment initiation. In addition, there was no consistent association with elevated acetylcholine antibody titres and the development of immune checkpoint inhibitor-related MG. Significantly, there was a 30.4% MG-specific-related mortality, which further emphasises the importance of early recognition and robust treatment of this toxicity. In addition to a review of the existing literature, we present a new case of pembrolizumab-induced MG and provide insights into the underlying mechanisms of action of this phenomenon. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Clinical Pharmacology Considerations for the Development of Immune Checkpoint Inhibitors.

    Science.gov (United States)

    Sheng, Jennifer; Srivastava, Shivani; Sanghavi, Kinjal; Lu, Zheng; Schmidt, Brian J; Bello, Akintunde; Gupta, Manish

    2017-10-01

    Immuno-oncology works through activation of the patient's immune system against cancer, with several advantages over other treatment approaches, including cytotoxic agents and molecular-targeted therapies. The most notable feature of immuno-oncology treatments is the nature of the patient responses achieved, which can be more durable and sustained than with other modalities. Increased understanding of immune system complexity has provided a number of opportunities to advance several strategies for the development of immuno-oncology therapies. This review outlines the clinical pharmacology characteristics and development challenges for the 6 approved immunomodulatory monoclonal antibodies that target 2 immune checkpoint pathways: ipilimumab (an anti-cytotoxic T-lymphocyte antigen-4 antibody) and, more recently, nivolumab and pembrolizumab (both anti-programmed death-1 antibodies) and atezolizumab, avelumab, and durvalumab (all anti-programmed death ligand-1 antibodies). These agents have revealed much about the clinical pharmacology features of immune checkpoint inhibitors as a class, as well as the pharmacometric approaches used to support their clinical development and regulatory approval. The development experiences with these pioneering immuno-oncology agents are likely to serve as useful guides in the discovery, progression, and approval of future drugs or combination of drugs in this class. This review includes summaries of the pharmacokinetics and exposure-response of the immune checkpoint inhibitors approved to date, as well as an overview of some quantitative systems pharmacology approaches. The ability of immuno-oncology to meet its full potential will depend on overcoming development challenges, including the need for clear strategies to determine optimal dose and scheduling for monotherapy as well as combination approaches. © 2017, The American College of Clinical Pharmacology.

  20. 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.

  1. 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

  2. Localization of checkpoint and repair proteins in eukaryotes

    DEFF Research Database (Denmark)

    Lisby, Michael; Rothstein, Rodney

    2005-01-01

    In eukaryotes, the cellular response to DNA damage depends on the type of DNA structure being recognized by the checkpoint and repair machinery. DNA ends and single-stranded DNA are hallmarks of double-strand breaks and replication stress. These two structures are recognized by distinct sets...... of proteins, which are reorganized into a focal assembly at the lesion. Moreover, the composition of these foci is coordinated with cell cycle progression, reflecting the favoring of end-joining in the G1 phase and homologous recombination in S and G2. The assembly of proteins at sites of DNA damage...... focusing on budding yeast and mammalian cells....

  3. Activation of repair and checkpoints by double-strand breaks of DNA. Activational cascade of protein phosphorylation

    International Nuclear Information System (INIS)

    Koltovaya, N.A.

    2007-01-01

    Molecular mechanisms of double-strand breaks repair and checkpoints include phosphorylations of repair and checkpoint-proteins by protein kinases. Chemical modification of proteins has different consequences including activation, changing of affinity to proteins and localization

  4. Twitter as a Tool to Warn Others about Sobriety Checkpoints: A Pilot Observational Study

    Science.gov (United States)

    Seitz, Christopher M.; Orsini, Muhsin Michael; Fearnow-Kenney, Melodie; Hatzudis, Kiki; Wyrick, David L.

    2012-01-01

    Anecdotal evidence suggests that young people use the website Twitter as a tool to warn drivers about the locations of sobriety checkpoints. Researchers investigated this claim by independently analyzing the website's content regarding a sample of 10 sobriety checkpoints that were conducted in cities throughout the United States during the weekend…

  5. Cdc20 and Cks direct the spindle checkpoint-independent destruction of cyclin A

    NARCIS (Netherlands)

    Wolthuis, Rob; Clay-Farrace, Lori; van Zon, Wouter; Yekezare, Mona; Koop, Lars; Ogink, Janneke; Medema, Rene; Pines, Jonathon

    2008-01-01

    Successful mitosis requires the right protein be degraded at the right time. Central to this is the spindle checkpoint that prevents the destruction of securin and cyclin 131 when there are improperly attached chromosomes. The principal target of the checkpoint is Cdc20, which activates the

  6. 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...

  7. 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

  8. Fanconi anemia cells with unrepaired DNA damage activate components of the checkpoint recovery process.

    Science.gov (United States)

    Rodríguez, Alfredo; Torres, Leda; Juárez, Ulises; Sosa, David; Azpeitia, Eugenio; García-de Teresa, Benilde; Cortés, Edith; Ortíz, Rocío; Salazar, Ana M; Ostrosky-Wegman, Patricia; Mendoza, Luis; Frías, Sara

    2015-09-18

    The FA/BRCA pathway repairs DNA interstrand crosslinks. Mutations in this pathway cause Fanconi anemia (FA), a chromosome instability syndrome with bone marrow failure and cancer predisposition. Upon DNA damage, normal and FA cells inhibit the cell cycle progression, until the G2/M checkpoint is turned off by the checkpoint recovery, which becomes activated when the DNA damage has been repaired. Interestingly, highly damaged FA cells seem to override the G2/M checkpoint. In this study we explored with a Boolean network model and key experiments whether checkpoint recovery activation occurs in FA cells with extensive unrepaired DNA damage. We performed synchronous/asynchronous simulations of the FA/BRCA pathway Boolean network model. FA-A and normal lymphoblastoid cell lines were used to study checkpoint and checkpoint recovery activation after DNA damage induction. The experimental approach included flow cytometry cell cycle analysis, cell division tracking, chromosome aberration analysis and gene expression analysis through qRT-PCR and western blot. Computational simulations suggested that in FA mutants checkpoint recovery activity inhibits the checkpoint components despite unrepaired DNA damage, a behavior that we did not observed in wild-type simulations. This result implies that FA cells would eventually reenter the cell cycle after a DNA damage induced G2/M checkpoint arrest, but before the damage has been fixed. We observed that FA-A cells activate the G2/M checkpoint and arrest in G2 phase, but eventually reach mitosis and divide with unrepaired DNA damage, thus resolving the initial checkpoint arrest. Based on our model result we look for ectopic activity of checkpoint recovery components. We found that checkpoint recovery components, such as PLK1, are expressed to a similar extent as normal undamaged cells do, even though FA-A cells harbor highly damaged DNA. Our results show that FA cells, despite extensive DNA damage, do not loss the capacity to express

  9. 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.

  10. [The pathology of adverse events with immune checkpoint inhibitors].

    Science.gov (United States)

    Koelzer, V H; Glatz, K; Bubendorf, L; Weber, A; Gaspert, A; Cathomas, G; Lugli, A; Zippelius, A; Kempf, W; Mertz, K D

    2017-05-01

    Immunotherapy has gained importance with the development of new effective cancer treatments. Immune checkpoint inhibitors (ICI) are monoclonal antibodies that promote T‑cell mediated tumor immune rejection. Checkpoint blockade also carries the risk of inducing autoimmune reactions ("immune related adverse events", irAEs). The diagnosis and classification of irAEs constitute a new and important field in pathology. Practice-oriented review of the diagnosis and classification of irAEs. Structured, selective literature review based on PubMed und UpToDate ® online. The most common irAEs affect the skin, the gastrointestinal tract, the liver, and the respiratory system. The correct diagnosis and classification of irAEs by an interdisciplinary care team is essential for appropriate therapy and the prevention of long-term sequelae. Other important irAEs affect the endocrine organs, the heart, the joints, the kidneys and the nervous system. Because of their rarity and/or limited options for bioptic diagnosis, only limited data on the morphology and pathophysiology of these irAEs are currently available. Autopsies carried out after ICI therapy constitute an important element of quality control and allow better documentation of the incidence and pathogenesis of irAEs. Pathology plays a central role in the diagnosis and treatment of irAEs. Future studies may contribute to a better mechanistic understanding of irAEs for individualized knowledge-based risk assessment.

  11. A smart checkpointing scheme for improving the reliability of clustering routing protocols.

    Science.gov (United States)

    Min, Hong; Jung, Jinman; Kim, Bongjae; Cho, Yookun; Heo, Junyoung; Yi, Sangho; Hong, Jiman

    2010-01-01

    In wireless sensor networks, system architectures and applications are designed to consider both resource constraints and scalability, because such networks are composed of numerous sensor nodes with various sensors and actuators, small memories, low-power microprocessors, radio modules, and batteries. Clustering routing protocols based on data aggregation schemes aimed at minimizing packet numbers have been proposed to meet these requirements. In clustering routing protocols, the cluster head plays an important role. The cluster head collects data from its member nodes and aggregates the collected data. To improve reliability and reduce recovery latency, we propose a checkpointing scheme for the cluster head. In the proposed scheme, backup nodes monitor and checkpoint the current state of the cluster head periodically. We also derive the checkpointing interval that maximizes reliability while using the same amount of energy consumed by clustering routing protocols that operate without checkpointing. Experimental comparisons with existing non-checkpointing schemes show that our scheme reduces both energy consumption and recovery latency.

  12. Detailed Modeling, Design, and Evaluation of a Scalable Multi-level Checkpointing System

    Energy Technology Data Exchange (ETDEWEB)

    Moody, A T; Bronevetsky, G; Mohror, K M; de Supinski, B R

    2010-04-09

    High-performance computing (HPC) systems are growing more powerful by utilizing more hardware components. As the system mean-time-before-failure correspondingly drops, applications must checkpoint more frequently to make progress. However, as the system memory sizes grow faster than the bandwidth to the parallel file system, the cost of checkpointing begins to dominate application run times. A potential solution to this problem is to use multi-level checkpointing, which employs multiple types of checkpoints with different costs and different levels of resiliency in a single run. The goal is to design light-weight checkpoints to handle the most common failure modes and rely on more expensive checkpoints for less common, but more severe failures. While this approach is theoretically promising, it has not been fully evaluated in a large-scale, production system context. To this end we have designed a system, called the Scalable Checkpoint/Restart (SCR) library, that writes checkpoints to storage on the compute nodes utilizing RAM, Flash, or disk, in addition to the parallel file system. We present the performance and reliability properties of SCR as well as a probabilistic Markov model that predicts its performance on current and future systems. We show that multi-level checkpointing improves efficiency on existing large-scale systems and that this benefit increases as the system size grows. In particular, we developed low-cost checkpoint schemes that are 100x-1000x faster than the parallel file system and effective against 85% of our system failures. This leads to a gain in machine efficiency of up to 35%, and it reduces the the load on the parallel file system by a factor of two on current and future systems.

  13. Coping with illegal immigrants.

    Science.gov (United States)

    Hewlett, S A

    1981-01-01

    The annual net flow of illegal immigrants into the US is around 500,000/year which has increased tenfold over the last 15 years; these people, unprotected by US law, are targets of exploitation. Unless a restrictive policy is put into practice for illegal and legal immigrants the flow will accelerate, creating domestic pressures. A package proposed by a Presidential Task Force in 1982 proposed: 1) there be better border patrols and stricter laws regarding hiring of illegals, 2) issuing a counterfeit-resistant social security card, 3) conditional amnesty for some illegal immigrants already in the US, 4) a small increase in the number of legal immigrants allowed into the US from Mexico, and 5) a limited guest worker program. These ideas differed in some respects from those of an earlier Select Committee on Immigration. Guest worker programs in other countries are described. In July 1982 President Reagan faced 3 policy options: 1) he could ignore his Task Force's ideas and use a large guest worker program, legalizing and continuing the inflow of cheap labor; 2) he could adopt the recommendations and get a new, tougher policy initiated; or 3) he could allow the issue to abort itself. He adopted the 3rd option, a policy package with little internal force which he will not pursue vigorously. Any serious effort to achieve a more serious immigration policy must include 4 elements: 1) a tough set of employer sanctions, 2) a foolproof worker identification card system, 3) better border control, and 4) an amnesty program. These 4 measures are interrelated; if 1 fails, the policy ceases to achieve its goals. This 4-point program would have the advantage of maintaining a short-term "safety-valve" for those countries which are the sources of illegal migration.

  14. Immigration reform, American style.

    Science.gov (United States)

    Papademetriou, D G

    1984-01-01

    This article reviews the background of the proposed Immigration and Reform Act (also known as the Simpson-Mazzoli bill), which seeks to overhaul US immigration law for the first time since 1952. This bill is consistent with President Reagan's hard line on border enforcement and mandates stiff penalties for those who transport illegal aliens for commercial advantage or private profit. It further offers Mexico preferential treatment in immigration (40,000 additional visas/year). It includes an amnesty program to offer legal status to qualified illegal residents. The bill directs the President to develop a secure national worker identification system and would create a large-scale temporary foreign agricultural program for perishable commodities. Agricultural workers' families would not be eligible to accompany them unless they also obtain temporary visas. Foreign temporary workers, employable only in cases where local domestic workers are not available, must be provided with wages and working conditions equal to those prevailing among domestic workers. Stiff penalties are stipulated for employers who fail to abide with the terms of the program. In the author's opinion, this bill fails to appreciate the global character of international migration and its complexity. It relects a fundamental ambivalence about a strictly controlled main gate versus a back door approach to immigration as well as the conflicting images of the US as a nation of immigrants versus the historical reality of American nativism and xenophobia. Needed are comprehensive initiatives whose mutually reinforcing components can address the multiple dimensions of the immigration problem within a framework that does not ignore workers who have contributed to the economic well-being of the US, regardless of their legal status.

  15. 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.

  16. 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...

  17. Immigrants' location preferences

    DEFF Research Database (Denmark)

    Damm, Anna Piil

    and lack of a local immigrant population by migrating to large municipalities. Lack of local fellow countrymen, however, increases the exit rate to medium-sized as well as large municipalities. This finding is likely to be a result of the dispersal policy. Finally, refugees react strongly to assignment......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...... to small municipalities by migrating mainly to medium-sized municipalities....

  18. 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.

  19. Immigration and the American century.

    Science.gov (United States)

    Hirschman, Charles

    2005-11-01

    The full impact of immigration on American society is obscured in policy and academic analyses that focus on the short-term problems of immigrant adjustment. With a longer-term perspective, which includes the socioeconomic roles of the children of immigrants, immigration appears as one of the defining characteristics of twentieth-century America. Major waves of immigration create population diversity with new languages and cultures, but over time, while immigrants and their descendants become more "American," the character of American society and culture is transformed. In the early decades of the twentieth century, immigrants and their children were the majority of the workforce in many of the largest industrial cities; in recent decades, the arrival of immigrants and their families has slowed the demographic and economic decline of some American cities. The presence of immigrants probably creates as many jobs for native-born workers as are lost through displacement. Immigrants and their children played an important role in twentieth-century American politics and were influential in the development of American popular culture during the middle decades of the twentieth century. Intermarriage between the descendants of immigrants and old-stock Americans fosters a national identity based on civic participation rather than ancestry.

  20. 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

  1. The politics of immigration reform.

    Science.gov (United States)

    Simpson, A K

    1984-01-01

    The US is the target for international migration, now more than ever. Population growth and economic stragnation in the Third World are increasing the pressures for out-migration, and current immigration law is wholly incapable of responding to the ever increasing flow of illegal immigrants. Border apprehensions of illegal aliens in the US were up 40% during 1983, and total apprehensions reached 1.25 million by the year's end. Recent public opinion polls have disclosed that an overwhelming majority of the American public demands immigration reform, and yet we as a nation have been distinctly unwilling or unable to respond to this clear public sentiment. This paper discusses the politics of the "Simpson-Mazzoli" Immigration Reform and Control Act, previous immigration legislation, current counterproposals for US immigration policy, and the political realities of immigration reform.

  2. Dynamics of immigration control.

    Science.gov (United States)

    Djajic, S

    1999-01-01

    This paper examines the dynamic implications of US border control policies and internal enforcement measures for the pattern of illegal immigration and the sectoral allocation of clandestine foreign workers. Efforts to counteract illegal immigration into the US have been increasing steadily following the passage of the Immigration Reform and Control Act of 1986. The purpose of the Act is to reduce illegal immigration with the aid of three instruments: 1) employer sanctions; 2) increased controls along the border; and 3) a legalization program designed to meet the existing demand for agricultural labor in geographic locations that are in proximity of Mexico, the principal source of clandestine foreign labor. The effect of tougher border control measures increases the cost of illegal entry, discouraging clandestine inflows. On the other hand, these measures induce migrants to increase their own anti-detection efforts, reducing the probability of detection and the deportation rate. If the latter effect should dominate, the steady-state stock of clandestine foreign labor will actually increase in response to more vigorous border control measures. Explicit consideration of the role of networks in the clandestine labor market suggests the need for a drastic policy change. This policy change should target illegal migration in areas with high concentrations of clandestine foreign workers. Complementary measures should accompany this policy change to prevent unbalanced enforcement measures.

  3. Detention of Immigrant Children.

    Science.gov (United States)

    Linton, Julie M; Griffin, Marsha; Shapiro, Alan J

    2017-05-01

    Immigrant children seeking safe haven in the United States, whether arriving unaccompanied or in family units, face a complicated evaluation and legal process from the point of arrival through permanent resettlement in communities. The conditions in which children are detained and the support services that are available to them are of great concern to pediatricians and other advocates for children. In accordance with internationally accepted rights of the child, immigrant and refugee children should be treated with dignity and respect and should not be exposed to conditions that may harm or traumatize them. The Department of Homeland Security facilities do not meet the basic standards for the care of children in residential settings. The recommendations in this statement call for limited exposure of any child to current Department of Homeland Security facilities (ie, Customs and Border Protection and Immigration and Customs Enforcement facilities) and for longitudinal evaluation of the health consequences of detention of immigrant children in the United States. From the moment children are in the custody of the United States, they deserve health care that meets guideline-based standards, treatment that mitigates harm or traumatization, and services that support their health and well-being. This policy statement also provides specific recommendations regarding postrelease services once a child is released into communities across the country, including a coordinated system that facilitates access to a medical home and consistent access to education, child care, interpretation services, and legal services. Copyright © 2017 by the American Academy of Pediatrics.

  4. Can immigrants hurt trade?

    Czech Academy of Sciences Publication Activity Database

    Konečný, Tomáš

    -, č. 329 (2007), s. 1-42 ISSN 1211-3298 R&D Projects: GA MŠk LC542 Institutional research plan: CEZ:AV0Z70850503 Keywords : immigrants * international trade * informal trade barriers Subject RIV: AH - Economics http://www.cerge-ei.cz/pdf/wp/Wp329.pdf

  5. 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...

  6. 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

  7. 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...

  8. 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.

  9. 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.

  10. 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

  11. EMODnet Black Sea Checkpoint First Data Adequacy Report

    Science.gov (United States)

    Pinardi, Nadia; Lyubartsev, Vladyslav; Manzella, Giuseppe; Palazov, Atanas; Slabakova, Violeta; Buga, Luminita; Kallos, George; Zodiatis, George; Stylianou, Stavros; Blanc, Frederique; Cesarini, Claudia

    2017-04-01

    The aim of the first Data Adequacy Report (DAR) of the EMODnet Black Sea Checkpoint project is to assess the basin scale monitoring systems on the basis of input data sets for 11 prescribed Challenges. The first step in this process involved the definition of a "Data Adequacy Framework", which was derived from the ISO 9004:2009 standards. Data Adequacy is essentially defined as the fitness for use of the monitoring data required by the Challenges. The CheckPoint adequacy relates to both the requirements as well as the needs of the Challenges and was developed considering the ISO 9001 Quality Management System. The quality assessment is subdivided into two major "territories": "appropriateness" and "availability". In the first DAR only the "availability" indicators are explored and analyzed. The second step in the analysis is to set up a metadatabase containing standardized information about the input datasets potentially usable by the Challenges to generate their products. The metadatabase is at the back-end of an INSPIRE Web and GIS platform, known as Sextant, and uses the SeaDataNet common vocabulary to identify the categories of characteristics needed by the Challenges and to analyze the statistics of indicators. The DAR contains the first assessment of the Black Sea monitoring system on the basis of the analysis of the availability indicators across all Challenges for the 452 input data sets and the 40 characteristic categories. The 8 availability indicators are classified based upon a three value range color system: "red" meaning "not adequate", "yellow" "partly adequate" and "green" "fully adequate". The analysis shows that for most of the indicators half are "not adequate" and the other half are "adequate". The single most negative score is for the "INSPIRE catalogue service" indicator, which is generally not adequate. Furthermore, the "Pricing" indicator is split in half between "not well documented pricing policy" and "open and free data policy". In

  12. Nuclear Molecular Imaging Strategies in Immune Checkpoint Inhibitor Therapy

    DEFF Research Database (Denmark)

    Guldbrandsen, Kasper F; Hendel, Helle W; Langer, Seppo W

    2017-01-01

    Immune checkpoint inhibitor therapy (ICT) is a new treatment strategy developed for the treatment of cancer. ICT inhibits pathways known to downregulate the innate immune response to cancer cells. These drugs have been shown to be effective in the treatment of a variety of cancers, including...... metastatic melanoma and lung cancer. Challenges in response evaluation of patients in ICT have risen as immune related side effects and immune cell infiltration may be confused with progressive disease. Furthermore, the timing of the evaluation scan may be challenged by relatively slow responses. To overcome......) as an alternative imaging method for monitoring patients undergoing ICT. Following the currently available evidence, this review will primarily focus on patients with malignant melanoma....

  13. 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...

  14. 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...

  15. 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...

  16. 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.

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

    OpenAIRE

    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 ex...

  18. 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....

  19. 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.

  20. 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

  1. 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)

  2. 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...

  3. Unauthorized Immigration and Electoral Outcomes

    OpenAIRE

    Baerg, Nicole Rae; Hotchkiss, Julie L.; Quispe-Agnoli, Myriam

    2014-01-01

    How do inflows of unauthorized immigrants shape elections? Political economy theories often yield competing predictions and mixed empirical results. The main hurdle of empirically evaluating the impact of unauthorized immigrants on election outcomes is finding reliable data that can measure unauthorized immigration flows over time. Using a unique methodology for identifying undocumented workers across counties in the state of Georgia in the United States, we find a positive relationship betwe...

  4. [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.

  5. [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

  6. 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...

  7. 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...

  8. Immigration: An Overview of Information Resources

    OpenAIRE

    Chapman, Bert

    2000-01-01

    Immigration has been a subject of intense historical and contemporary debate in US political life. Proponents of immigration cite the important contributions immigrants have made and continue to make to the USA’s national development and evolution. Advocates of more restrictive immigration policies stress concerns over the USA’s ability to support immigrant residents and whether newer immigrants threaten the US national identity and social cohesion. Proponents and opponents of current US i...

  9. 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...

  10. CDK9 inhibitors define elongation checkpoints at both ends of RNA polymerase II-transcribed genes.

    Science.gov (United States)

    Laitem, Clélia; Zaborowska, Justyna; Isa, Nur F; Kufs, Johann; Dienstbier, Martin; Murphy, Shona

    2015-05-01

    Transcription through early-elongation checkpoints requires phosphorylation of negative transcription elongation factors (NTEFs) by the cyclin-dependent kinase (CDK) 9. Using CDK9 inhibitors and global run-on sequencing (GRO-seq), we have mapped CDK9 inhibitor-sensitive checkpoints genome wide in human cells. Our data indicate that early-elongation checkpoints are a general feature of RNA polymerase (pol) II-transcribed human genes and occur independently of polymerase stalling. Pol II that has negotiated the early-elongation checkpoint can elongate in the presence of inhibitors but, remarkably, terminates transcription prematurely close to the terminal polyadenylation (poly(A)) site. Our analysis has revealed an unexpected poly(A)-associated elongation checkpoint, which has major implications for the regulation of gene expression. Interestingly, the pattern of modification of the C-terminal domain of pol II terminated at this new checkpoint largely mirrors the pattern normally found downstream of the poly(A) site, thus suggesting common mechanisms of termination.

  11. Human cytomegalovirus inhibits a DNA damage response by mislocalizing checkpoint proteins

    Science.gov (United States)

    Gaspar, Miguel; Shenk, Thomas

    2006-02-01

    The DNA damage checkpoint pathway responds to DNA damage and induces a cell cycle arrest to allow time for DNA repair. Several viruses are known to activate or modulate this cellular response. Here we show that the ataxia-telangiectasia mutated checkpoint pathway, which responds to double-strand breaks in DNA, is activated in response to human cytomegalovirus DNA replication. However, this activation does not propagate through the pathway; it is blocked at the level of the effector kinase, checkpoint kinase 2 (Chk2). Late after infection, several checkpoint proteins, including ataxia-telangiectasia mutated and Chk2, are mislocalized to a cytoplasmic virus assembly zone, where they are colocalized with virion structural proteins. This colocalization was confirmed by immunoprecipitation of virion proteins with an antibody that recognizes Chk2. Virus replication was resistant to ionizing radiation, which causes double-strand breaks in DNA. We propose that human CMV DNA replication activates the checkpoint response to DNA double-strand breaks, and the virus responds by altering the localization of checkpoint proteins to the cytoplasm and thereby inhibiting the signaling pathway. ionizing radiation | ataxia-telangiectasia mutated pathway

  12. Topoisomerase II Inhibitors and Poisons, and the Influence of Cell Cycle Checkpoints.

    Science.gov (United States)

    D Arcy, Nicholas; Gabrielli, Brian

    2017-01-01

    Interactions between the decatenation checkpoint and Topoisomerase II (TopoII) are vital for maintaining integrity of the genome. Agents that target this enzyme have been in clinical use in cancer therapy for over 30 years with great success. The types of compounds that have been developed to target TopoII are broadly divided into poisons and catalytic inhibitors. The TopoII poisons are in clinical use as anti-cancer therapies, although in common to most chemotherapeutic agents, they display considerable normal tissue toxicity. Inhibition of the TopoIIb isoform has been implicated in this cytotoxicity. Response to TopoII active agents is determined by several factors, but cell cycle checkpoints play a large role in sensitivity and resistance. The G2/M phase checkpoints are of particular importance in considering the effectiveness of these drugs and are reviewed in this article. Functionality of the ATM dependent decatenation checkpoint may represent a new avenue for selective cancer therapy. Here we review the function of TopoII, the anti-cancer mechanisms and limitations of current catalytic inhibitors and poisons, and their influence on cell cycle checkpoints. We will also assess potential new mechanisms for targeting this enzyme to limit normal tissue toxicity, and how the cell cycle checkpoint triggered by these drugs may provide an alternative and possibly better target for novel therapies. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  13. The Evolving Role of Immune Checkpoint Inhibitors in Cancer Treatment.

    Science.gov (United States)

    Pennock, Gregory K; Chow, Laura Q M

    2015-07-01

    Traditional treatment modalities for advanced cancer (radiotherapy, chemotherapy, or targeted agents) act directly on tumors to inhibit or destroy them. Along with surgery, these modalities are predominantly palliative, with toxicity and only modest improvements in survival in patients with advanced solid tumors. Accordingly, long-term survival rates for most patients with advanced cancer remain low, thus there is a need for cancer treatments with favorable benefit and toxicity profiles that can potentially result in long-term survival. The immune system plays a critical role in the recognition and eradication of tumor cells ("immune surveillance"), and immunotherapies based on this concept have been used for decades with some success against a few tumor types; however, most immunotherapies were limited by a lack of either substantial efficacy or specificity, resulting in toxicity. We now have a greater understanding of the complex interactions between the immune system and tumors and have identified key molecules that govern these interactions. This information has revitalized the interest in immunotherapy as an evolving treatment modality using immunotherapeutics designed to overcome the mechanisms exploited by tumors to evade immune destruction. Immunotherapies have potentially complementary mechanisms of action that may allow them to be combined with other immunotherapeutics, chemotherapy, targeted therapy, or other traditional therapies. This review discusses the concepts and data behind immunotherapies, with a focus on the checkpoint inhibitors and their responses, toxicities, and potential for long-term survival, and explores promising single-agent and combination therapies in development. Immunotherapy is an evolving treatment approach based on the role of the immune system in eradicating cancer. An example of an immunotherapeutic is ipilimumab, an antibody that blocks cytotoxic T-lymphocyte antigen-4 (CTLA-4) to augment antitumor immune responses

  14. United States Immigration Policy and Indirect Immigration of Professionals.

    Science.gov (United States)

    Agarwal, Vinod B.; Winkler, Donald R.

    1985-01-01

    The number of foreign professionals (including college students) who have entered the United States with nonimmigrant status but who have their visas adjusted to immigrant status is steadily increasing. This study explores the relationship between the frequency of such adjustments and changes in immigration policy. (PGD)

  15. Mismatch Repair Deficiency and Response to Immune Checkpoint Blockade.

    Science.gov (United States)

    Lee, Valerie; Murphy, Adrian; Le, Dung T; Diaz, Luis A

    2016-10-01

    : More than 1.6 million new cases of cancer will be diagnosed in the U.S. in 2016, resulting in more than 500,000 deaths. Although chemotherapy has been the mainstay of treatment in advanced cancers, immunotherapy development, particularly with PD-1 inhibitors, has changed the face of treatment for a number of tumor types. One example is the subset of tumors characterized by mismatch repair deficiency and microsatellite instability that are highly sensitive to PD-1 blockade. Hereditary forms of cancer have been noted for more than a century, but the molecular changes underlying mismatch repair-deficient tumors and subsequent microsatellite unstable tumors was not known until the early 1990s. In this review article, we discuss the history and pathophysiology of mismatch repair, the process of testing for mismatch repair deficiency and microsatellite instability, and the role of immunotherapy in this subset of cancers. Mismatch repair deficiency has contributed to our understanding of carcinogenesis for the past 2 decades and now identifies a subgroup of traditionally chemotherapy-insensitive solid tumors as sensitive to PD-1 blockade. This article seeks to educate oncologists regarding the nature of mismatch repair deficiency, its impact in multiple tumor types, and its implications for predicting the responsiveness of solid tumors to immune checkpoint blockade. ©AlphaMed Press.

  16. 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

  17. Wi-Fi location fingerprinting using an intelligent checkpoint sequence

    Science.gov (United States)

    Retscher, Günther; Hofer, Hannes

    2017-09-01

    For Wi-Fi positioning location fingerprinting is very common but has the disadvantage that it is very labour consuming for the establishment of a database (DB) with received signal strength (RSS) scans measured on a large number of known reference points (RPs). To overcome this drawback a novel approach is developed which uses a logical sequence of intelligent checkpoints (iCPs) instead of RPs distributed in a regular grid. The iCPs are the selected RPs which have to be passed along the way for navigation from a start point A to the destination B. They are twofold intelligent because of the fact that they depend on their meaningful selection and because of their logical sequence in their correct order. Thus, always the following iCP is known due to a vector graph allocation in the DB and only a small limited number of iCPs needs to be tested when matching the current RSS scans. This reduces the required processing time significantly. It is proven that the iCP approach achieves a higher success rate than conventional approaches. In average correct matching results of 90.0% were achieved using a joint DB including RSS scans of all employed smartphones. An even higher success rate is achieved if the same mobile device is used in both the training and positioning phase.

  18. 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...

  19. Illegal Immigration. Opposing Viewpoints Series.

    Science.gov (United States)

    Cozic, Charles P., Ed.

    Books in the Opposing Viewpoints Series present debates about current issues that can be used to teach critical reading and thinking skills. The variety of opinions expressed in this collection of articles and book excerpts explore many aspects of illegal immigration. Contrary depictions of the aspirations and attitudes of illegal immigrants fuel…

  20. 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.

  1. 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.

  2. Nation and Immigration

    Directory of Open Access Journals (Sweden)

    Ali Behdad

    2005-08-01

    Full Text Available In my paper, I wish to offer a critical assessment of the cultural and political implications of postcolonial and cultural critics’ abandonment of situated terms like immigration, citizenship, race, state, and their celebratory embracing of such unmoored notions as nomadism, deterritorialization, exile, hybridy, and postnation. On the one hand, I hope to demonstrate that postcolonial critics’ valorization of displacement’s redemptive power mystifies the oppositional possibilities of hybrid consciousness. On the other, I wish to argue that such theoretical projects fail to both historicize the particularities of postcolonial cultural formations and the importance of the politics of location in describing various manifestations of the global.

  3. The unstoppable immigrant.

    Science.gov (United States)

    Tapinos, G P

    1990-01-01

    The author examines the effects of the restrictive immigration policies instituted by the European countries in the mid-1970s. "This article considers the following questions. Should one expect significant migrant supply pressure from the countries that formerly sent workers, as a result of their demographic, economic and labour market prospects? Have the European countries devised any development-assistance policy with the explicit intent of cutting down emigration from these countries? And would such a policy, if it existed, be efficient enough to decrease the incentives to migrate?" excerpt

  4. Context-dependent cell cycle checkpoint abrogation by a novel kinase inhibitor.

    Directory of Open Access Journals (Sweden)

    Andrew J Massey

    2010-10-01

    Full Text Available Checkpoint kinase 1 and 2 (Chk1/Chk2, and the Aurora kinases play a critical role in the activation of the DNA damage response and mitotic spindle checkpoints. We have identified a novel inhibitor of these kinases and utilized this molecule to probe the functional interplay between these two checkpoints.Fragment screening, structure guided design, and kinase cross screening resulted in the identification of a novel, potent small molecule kinase inhibitor (VER-150548 of Chk1 and Chk2 kinases with IC(50s of 35 and 34 nM as well as the Aurora A and Aurora B kinases with IC(50s of 101 and 38 nM. The structural rationale for this kinase specificity could be clearly elucidated through the X-ray crystal structure. In human carcinoma cells, VER-150548 induced reduplication and the accumulation of cells with >4N DNA content, inhibited histone H3 phosphorylation and ultimately gave way to cell death after 120 hour exposure; a phenotype consistent with cellular Aurora inhibition. In the presence of DNA damage induced by cytotoxic chemotherapeutic drugs, VER-150548 abrogated DNA damage induced cell cycle checkpoints. Abrogation of these checkpoints correlated with increased DNA damage and rapid cell death in p53 defective HT29 cells. In the presence of DNA damage, reduplication could not be observed. These observations are consistent with the Chk1 and Chk2 inhibitory activity of this molecule.In the presence of DNA damage, we suggest that VER-150548 abrogates the DNA damage induced checkpoints forcing cells to undergo a lethal mitosis. The timing of this premature cell death induced by Chk1 inhibition negates Aurora inhibition thereby preventing re-entry into the cell cycle and subsequent DNA reduplication. This novel kinase inhibitor therefore serves as a useful chemical probe to further understand the temporal relationship between cell cycle checkpoint pathways, chemotherapeutic agent induced DNA damage and cell death.

  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. 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.

  7. 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.

  8. 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…

  9. Sponsors, Sponsorship Rates and the Immigration Multiplier.

    Science.gov (United States)

    Jasso, Guillermina; Rosenzweig, Mark R.

    1989-01-01

    Reviews evidence of the extent to which U.S. immigrants utilize the family reunification entitlements of immigration laws. Examines two studies of the immigrant cohort: Jasso and Rosenzweig (1986) and the General Accounting Office report (1988). Provides estimates of the characteristics of U.S. citizen sponsors of immigrant spouses and parents.…

  10. 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...

  11. Languages of Immigrants as Modern Foreign Languages.

    Science.gov (United States)

    Reich, Hans H.; Pornbacher, Ulrike

    Policy and planning concerning the minority languages of immigrants are discussed, focusing on three countries receiving many immigrants: England, France, and Germany. First, similarities and differences in the immigration histories of the three countries, and in their policies concerning education of immigrants, are examined. Then policy…

  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. Modulations of cell cycle checkpoints during HCV associated disease

    Directory of Open Access Journals (Sweden)

    Jafri Wasim

    2009-08-01

    Full Text Available Abstract Background Impaired proliferation of hepatocytes has been reported in chronic Hepatitis C virus infection. Considering the fundamental role played by cell cycle proteins in controlling cell proliferation, altered regulation of these proteins could significantly contribute to HCV disease progression and subsequent hepatocellular carcinoma (HCC. This study aimed to identify the alterations in cell cycle genes expression with respect to early and advanced disease of chronic HCV infection. Methods Using freshly frozen liver biopsies, mRNA levels of 84 cell cycle genes in pooled RNA samples from patients with early or advanced fibrosis of chronic HCV infection were studied. To associate mRNA levels with respective protein levels, four genes (p27, p15, KNTC1 and MAD2L1 with significant changes in mRNA levels (> 2-fold, p-value Results In the early fibrosis group, increased mRNA levels of cell proliferation genes as well as cell cycle inhibitor genes were observed. In the advanced fibrosis group, DNA damage response genes were up-regulated while those associated with chromosomal stability were down-regulated. Increased expression of CDK inhibitor protein p27 was consistent with its mRNA level detected in early group while the same was found to be negatively associated with liver fibrosis. CDK inhibitor protein p15 was highly expressed in both early and advanced group, but showed no correlation with fibrosis. Among the mitotic checkpoint regulators, expression of KNTC1 was significantly reduced in advanced group while MAD2L1 showed a non-significant decrease. Conclusion Collectively these results are suggestive of a disrupted cell cycle regulation in HCV-infected liver. The information presented here highlights the potential of identified proteins as predictive factors to identify patients with high risk of cell transformation and HCC development.

  15. 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

  16. 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.

  17. Preserving Yeast Genetic Heritage through DNA Damage Checkpoint Regulation and Telomere Maintenance

    Directory of Open Access Journals (Sweden)

    Huilin Zhou

    2012-10-01

    Full Text Available In order to preserve genome integrity, extrinsic or intrinsic DNA damages must be repaired before they accumulate in cells and trigger other mutations and genome rearrangements. Eukaryotic cells are able to respond to different genotoxic stresses as well as to single DNA double strand breaks (DSBs, suggesting highly sensitive and robust mechanisms to detect lesions that trigger a signal transduction cascade which, in turn, controls the DNA damage response (DDR. Furthermore, cells must be able to distinguish natural chromosomal ends from DNA DSBs in order to prevent inappropriate checkpoint activation, DDR and chromosomal rearrangements. Since the original discovery of RAD9, the first DNA damage checkpoint gene identified in Saccharomyces cerevisiae, many genes that have a role in this pathway have been identified, including MRC1, MEC3, RAD24, RAD53, DUN1, MEC1 and TEL1. Extensive studies have established most of the genetic basis of the DNA damage checkpoint and uncovered its different functions in cell cycle regulation, DNA replication and repair, and telomere maintenance. However, major questions concerning the regulation and functions of the DNA damage checkpoint remain to be answered. First, how is the checkpoint activity coupled to DNA replication and repair? Second, how do cells distinguish natural chromosome ends from deleterious DNA DSBs? In this review we will examine primarily studies performed using Saccharomyces cerevisiae as a model system.

  18. Immigration: an international economic perspective.

    Science.gov (United States)

    Marshall, R

    1984-01-01

    The creation of an effective US immigration policy has been complicated by the diversity of political interests and the absence of reliable statistics to determine the magnitude of the impact on the American economy. Estimates of the number of illegal aliens in the US range from 1 to 12 million. While political biases and complexities and data inadequacies complicate this analysis, some generalizations seem to be confirmed by worldwide experience. There are 2 mutually-supportive, short-run ways to reduce the flow of undocumented workers: 1) to better police US borders and shorelines and 2) to remove the motive for entry by making it illegal for employers to hire workers who are not authorized to work in the US. To give employers an easy defense and to facilitate their compliance with immigration laws, an effective worker identification system should be developed. To avoid the civil liberties, international relations, and human problems associated with mass deportations, illegal immigrants who entered the US before January 1, 1981 and who have been in continuous residence for at least 1 year, should be permitted to remain in the US as permanent resident aliens. The US should not adopt a new guest worker program. The proper sequence of changes in immigration policy is very important. Dealing with illegal immigration is essential; all these measures should be in place before an amnesty is granted. Because it is important to have friendly relations with neighboring countries and because the ultimate solution to illegal immigration is to reduce the wide disparities in employment opportunities between countries, the US should work with other countries to control illegal immigration, but should not link control to energy, trade, or other policies. It is particularly important to discuss immigration control plans with other countries, especially Mexico, and to do everything consistent with US interests to minimize the adverse impact of our immigration policies on our

  19. Political instability and illegal immigration.

    Science.gov (United States)

    Campos, J E; Lien, D

    1995-01-01

    "Economic theory suggests that transnational migration results from the push-pull effect of wage differentials between host and source countries. In this paper, we argue that political instability exacerbates the migration flow, with greater instability leading to relatively larger flows. We conclude then that an optimal solution to the illegal immigration problem requires proper coordination of immigration and foreign policies by the host country. A narrow preoccupation with tougher immigration laws is wasteful and may be marginally effective." Emphasis is on the United States as a host country. excerpt

  20. Immigrant unemployment: the Australian experience.

    Science.gov (United States)

    Miller, P W; Neo, L M

    1997-01-01

    "Between 1980 and 1996 both male and female immigrants experienced higher unemployment rates than Australia-born workers....A multivariate analysis is used in this article to examine unemployment rate differentials between Australia-born and immigrants from English-speaking countries and immigrants from non-English-speaking countries. A feature of the analysis is decomposition of unemployment rate differences between birthplace groups into a component attributable to the different characteristics of the birthplace groups (e.g. different mean levels of education) and a part that is viewed as an impact associated simply with being foreign born." (EXCERPT)

  1. How Do Tougher Immigration Measures Affect Unauthorized Immigrants?

    Science.gov (United States)

    Amuedo-Dorantes, Catalina; Puttitanun, Thitima; Martinez-Donate, Ana P.

    2013-01-01

    The recent impetus of tougher immigration-related measures passed at the state level raises concerns about the impact of such measures on the migration experience, trajectory, and future plans of unauthorized immigrants. In a recent and unique survey of Mexican unauthorized immigrants interviewed upon their voluntary return or deportation to Mexico, almost a third reported experiencing difficulties in obtaining social or government services, finding legal assistance, or obtaining health care services. Additionally, half of these unauthorized immigrants reported fearing deportation. When we assess how the enactment of punitive measures against unauthorized immigrants, such as E-Verify mandates, has affected their migration experience, we find no evidence of a statistically significant association between these measures and the difficulties reported by unauthorized immigrants in accessing a variety of services. However, the enactment of these mandates infuses deportation fear, reduces interstate mobility among voluntary returnees during their last migration spell, and helps curb deportees’ intent to return to the United States in the near future. PMID:23532619

  2. 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.

  3. 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

  4. 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.

  5. 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.

  6. Shaping tolerant attitudes towards immigrants

    DEFF Research Database (Denmark)

    Rapp, Carolin

    2017-01-01

    civil societies cope with rising levels of diversity stemming from increased immigration and individualism. Within the tolerance literature, it is commonly agreed upon that a comprehensive welfare state is capable of bridging class divides and overcoming social categorization. However, over the past...... decades, European welfare states experienced an ongoing influx of immigrants, challenging their general purpose and increasing notions of ‘welfare chauvinism’. Drawing on insights from both tolerance and welfare state solidarity literature, we implement hierarchical analyses based on Eurobarometer data...

  7. 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 ...

  8. 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.

  9. Bub1 positions Mad1 close to KNL1 MELT repeats to promote checkpoint signalling

    DEFF Research Database (Denmark)

    Zhang, Gang; Kruse, Thomas; López-Méndez, Blanca

    2017-01-01

    Proper segregation of chromosomes depends on a functional spindle assembly checkpoint (SAC) and requires kinetochore localization of the Bub1 and Mad1/Mad2 checkpoint proteins. Several aspects of Mad1/Mad2 kinetochore recruitment in human cells are unclear and in particular the underlying direct...... interactions. Here we show that conserved domain 1 (CD1) in human Bub1 binds directly to Mad1 and a phosphorylation site exists in CD1 that stimulates Mad1 binding and SAC signalling. Importantly, fusion of minimal kinetochore-targeting Bub1 fragments to Mad1 bypasses the need for CD1, revealing that the main...

  10. 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...

  11. Functional and Physical Interaction between Rad24 and Rfc5 in the Yeast Checkpoint Pathways

    OpenAIRE

    Shimomura, Toshiyasu; Ando, Seiko; Matsumoto, Kunihiro; Sugimoto, Katsunori

    1998-01-01

    The RFC5 gene encodes a small subunit of replication factor C (RFC) complex in Saccharomyces cerevisiae and has been shown to be required for the checkpoints which respond to replication block and DNA damage. Here we describe the isolation of RAD24, known to play a role in the DNA damage checkpoint, as a dosage-dependent suppressor of rfc5-1. RAD24 overexpression suppresses the sensitivity of rfc5-1 cells to DNA-damaging agents and the defect in DNA damage-induced Rad53 phosphorylation. Rad24...

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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... IMMIGRATION REVIEW § 3.0 Executive Office for Immigration Review Regulations of the Executive Office for Immigration Review relating to the adjudication of immigration matters before immigration judges (referred to...

  18. 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.

  19. Noncoding RNAs and immune checkpoints-clinical implications as cancer therapeutics.

    Science.gov (United States)

    Smolle, Maria A; Calin, Horatiu N; Pichler, Martin; Calin, George A

    2017-07-01

    A major mechanism of tumor development and progression is silencing of the patient's immune response to cancer-specific antigens. Defects in the so-called cancer immunity cycle may occur at any stage of tumor development. Within the tumor microenvironment, aberrant expression of immune checkpoint molecules with activating or inhibitory effects on T lymphocytes induces immune tolerance and cellular immune escape. Targeting immune checkpoint molecules such as programmed cell death protein 1 (PD-1) and its ligand PD-L1 with specific antibodies has proven to be a major advance in the treatment of several types of cancer. Another way to therapeutically influence the tumor microenvironment is by modulating the levels of microRNAs (miRNAs), small noncoding RNAs that shuttle bidirectionally between malignant and tumor microenvironmental cells. These small RNA transcripts have two features: (a) their expression is quite specific to distinct tumors, and (b) they are involved in early regulation of immune responses. Consequently, miRNAs may be ideal molecules for use in cancer therapy. Many miRNAs are aberrantly expressed in human cancer cells, opening new opportunities for cancer therapy, but the exact functions of these miRNAs and their interactions with immune checkpoint molecules have yet to be investigated. This review summarizes recently reported findings about miRNAs as modulators of immune checkpoint molecules and their potential application as cancer therapeutics in clinical practice. © 2017 Federation of European Biochemical Societies.

  20. HLA dependent immune escape mechanisms in B-cell lymphomas : Implications for immune checkpoint inhibitor therapy?

    NARCIS (Netherlands)

    Nijland, Marcel; Veenstra, Rianne N.; Visser, Lydia; Xu, Chuanhui; Kushekhar, Kushi; van Imhoff, Gustaaf W.; Kluin, Philip M.; van den Berg, Anke; Diepstra, Arjan

    2017-01-01

    Antigen presentation by tumor cells in the context of Human Leukocyte Antigen (HLA) is generally considered to be a prerequisite for effective immune checkpoint inhibitor therapy. We evaluated cell surface HLA class I, HLA class II and cytoplasmic HLA-DM staining by immunohistochemistry (IHC) in 389

  1. 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...

  2. Checkpoint recovery in cells: how a molecular understanding can help in the fight against cancer

    Czech Academy of Sciences Publication Activity Database

    Medema, R.H.; Macůrek, Libor

    2011-01-01

    Roč. 3, - (2011), e10 ISSN 1757-594X R&D Projects: GA ČR GAP301/10/1525; GA ČR GPP305/10/P420 Institutional research plan: CEZ:AV0Z50520514 Keywords : checkpoint * DNA damage * cancer Subject RIV: EB - Genetics ; Molecular Biology

  3. Immune checkpoint inhibition-related colitis: symptoms, endoscopic features, histology and response to management.

    NARCIS (Netherlands)

    Geukes Foppen, M.H.; Rozeman, E.A.; Wilpe, S. van; Postma, C.; Snaebjornsson, P.; Thienen, J.V. van; Leerdam, M.E. van; Heuvel, M. van den; Blank, C.U.; Dieren, J. van; Haanen, J.B.A.G.

    2018-01-01

    Background: Immune checkpoint inhibitors are successfully introduced as anticancer treatment. However, they may induce severe immune-related adverse events (irAEs). One of the most frequent irAEs is diarrhoea. The main objective of this study was to analyse symptoms (ie, grade of diarrhoea),

  4. Dynamics of Immune Checkpoints, Immune System, and BCG in the Treatment of Superficial Bladder Cancer

    Directory of Open Access Journals (Sweden)

    Farouk Tijjani Saad

    2017-01-01

    Full Text Available This paper aims to study the dynamics of immune suppressors/checkpoints, immune system, and BCG in the treatment of superficial bladder cancer. Programmed cell death protein-1 (PD-1, cytotoxic T-lymphocyte-associated antigen 4 (CTLA4, and transforming growth factor-beta (TGF-β are some of the examples of immune suppressors/checkpoints. They are responsible for deactivating the immune system and enhancing immunological tolerance. Moreover, they categorically downregulate and suppress the immune system by preventing and blocking the activation of T-cells, which in turn decreases autoimmunity and enhances self-tolerance. In cancer immunotherapy, the immune checkpoints/suppressors prevent and block the immune cells from attacking, spreading, and killing the cancer cells, which leads to cancer growth and development. We formulate a mathematical model that studies three possible dynamics of the treatment and establish the effects of the immune checkpoints on the immune system and the treatment at large. Although the effect cannot be seen explicitly in the analysis of the model, we show it by numerical simulations.

  5. 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

  6. 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.

  7. Clonal neoantigens elicit T cell immunoreactivity and sensitivity to immune checkpoint blockade

    DEFF Research Database (Denmark)

    McGranahan, Nicholas; Furness, Andrew J S; Rosenthal, Rachel

    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...

  8. Checkpoint-Independent Regulation of Origin Firing by Mrc1 through Interaction with Hsk1 Kinase.

    Science.gov (United States)

    Matsumoto, Seiji; Kanoh, Yutaka; Shimmoto, Michie; Hayano, Motoshi; Ueda, Kyosuke; Fukatsu, Rino; Kakusho, Naoko; Masai, Hisao

    2017-04-01

    Mrc1 is a conserved checkpoint mediator protein that transduces the replication stress signal to the downstream effector kinase. The loss of mrc1 checkpoint activity results in the aberrant activation of late/dormant origins in the presence of hydroxyurea. Mrc1 was also suggested to regulate orders of early origin firing in a checkpoint-independent manner, but its mechanism was unknown. Here we identify HBS (Hsk1 bypass segment) on Mrc1. An Δ HBS mutant does not activate late/dormant origin firing in the presence of hydroxyurea but causes the precocious and enhanced activation of weak early-firing origins during normal S-phase progression and bypasses the requirement for Hsk1 for growth. This may be caused by the disruption of intramolecular binding between HBS and NTHBS (N-terminal target of HBS). Hsk1 binds to Mrc1 through HBS and phosphorylates a segment adjacent to NTHBS, disrupting the intramolecular interaction. We propose that Mrc1 exerts a "brake" on initiation (through intramolecular interactions) and that this brake can be released (upon the loss of intramolecular interactions) by either the Hsk1-mediated phosphorylation of Mrc1 or the deletion of HBS (or a phosphomimic mutation of putative Hsk1 target serine/threonine), which can bypass the function of Hsk1 for growth. The brake mechanism may explain the checkpoint-independent regulation of early origin firing in fission yeast. Copyright © 2017 American Society for Microbiology.

  9. 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

    The cell has many mechanisms for protecting the integrity of its genome. These mechanisms are often weakened or absent in many cancers, leading to high rates of chromosomal instability in tumors. Control of the cell cycle is crucial for the function of these checkpoints, and is frequently lost in...

  10. 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.

  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. 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

  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. A Description of the Immigrant Population

    National Research Council Canada - National Science Library

    Brauer, David

    2004-01-01

    .... Immigrants also contribute to the economy and pay taxes. A major question is whether immigration has the potential to lessen the strain on the federal budget as the baby-boom generation retires...

  15. Social Exclusion among Peers: The Role of Immigrant Status and Classroom Immigrant Density.

    Science.gov (United States)

    Plenty, Stephanie; Jonsson, Jan O

    2017-06-01

    Increasing immigration and school ethnic segregation have raised concerns about the social integration of minority students. We examined the role of immigrant status in social exclusion and the moderating effect of classroom immigrant density among Swedish 14-15-year olds (n = 4795, 51 % females), extending conventional models of exclusion by studying multiple outcomes: victimization, isolation, and rejection. Students with immigrant backgrounds were rejected more than majority youth and first generation non-European immigrants were more isolated. Immigrants generally experienced more social exclusion in immigrant sparse than immigrant dense classrooms, and victimization increased with higher immigrant density for majority youth. The findings demonstrate that, in addition to victimization, subtle forms of exclusion may impede the social integration of immigrant youth but that time in the host country alleviates some risks for exclusion.

  16. 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.

  17. The meiotic recombination checkpoint suppresses NHK-1 kinase to prevent reorganisation of the oocyte nucleus in Drosophila.

    Directory of Open Access Journals (Sweden)

    Oscar M Lancaster

    2010-10-01

    Full Text Available The meiotic recombination checkpoint is a signalling pathway that blocks meiotic progression when the repair of DNA breaks formed during recombination is delayed. In comparison to the signalling pathway itself, however, the molecular targets of the checkpoint that control meiotic progression are not well understood in metazoans. In Drosophila, activation of the meiotic checkpoint is known to prevent formation of the karyosome, a meiosis-specific organisation of chromosomes, but the molecular pathway by which this occurs remains to be identified. Here we show that the conserved kinase NHK-1 (Drosophila Vrk-1 is a crucial meiotic regulator controlled by the meiotic checkpoint. An nhk-1 mutation, whilst resulting in karyosome defects, does so independent of meiotic checkpoint activation. Rather, we find unrepaired DNA breaks formed during recombination suppress NHK-1 activity (inferred from the phosphorylation level of one of its substrates through the meiotic checkpoint. Additionally DNA breaks induced by X-rays in cultured cells also suppress NHK-1 kinase activity. Unrepaired DNA breaks in oocytes also delay other NHK-1 dependent nuclear events, such as synaptonemal complex disassembly and condensin loading onto chromosomes. Therefore we propose that NHK-1 is a crucial regulator of meiosis and that the meiotic checkpoint suppresses NHK-1 activity to prevent oocyte nuclear reorganisation until DNA breaks are repaired.

  18. 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

  19. 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

  20. 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

  1. 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...

  2. 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 ...

  3. 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…

  4. How Do Immigrants Affect Us Economically?

    Science.gov (United States)

    Simon, Julian L.

    This document summarizes the key data and main findings of the book, "The Economic Consequences of Immigration into the United States." All immigrants, not only those who are illegal, are included in the discussion. Immigrants, it is concluded, raise the standard of living of the residents of the host country, rather than lowering it as is…

  5. Beyond "Culture Clash" Understandings of Immigrant Experiences

    Science.gov (United States)

    Ngo, Bic

    2008-01-01

    This article addresses the ways in which the experiences of immigrant youth and families in U.S. schools and society have been conceptualized primarily as conflicts between immigrant cultures and dominant U.S. culture. Exemplified by the discourse of culture clash or of immigrants being torn between two worlds, this prevalent understanding…

  6. 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

  7. New Orthodox Immigration in Finland

    Directory of Open Access Journals (Sweden)

    Tuomas Martikainen

    2005-01-01

    Full Text Available The Finnish Orthodox Church is the second largest religious organization in Finland with ca. 57,000 members. During the last 15 years its membership has grown 7% because of international migration. The migrants are mainly from the former Soviet Union (e.g. Estonia, Russia and Ukraine, but there are also small groups from, e.g., Greece, Ethiopia and Romania. The article is a case study of the immigrant activities in two Orthodox parishes that are located in Helsinki and Turku. Issues such as organizational support, religious education and transnational connections are presented. Based on contemporary research on religion and immigration, the article aims to highlight the speci? c role of language in immigrant organizations, and it argues that more attention should be given to it as a speci? c factor.

  8. Immigrants in the Sexual Revolution

    DEFF Research Database (Denmark)

    Shield, Andrew DJ

    This book focuses on the latter half of the twentieth century, when much of northwest Europe grew increasingly multicultural with the arrival of foreign workers and (post-)colonial migrants, whilst simultaneously experiencing a boom in feminist and sexual liberation activism. Using multilingual...... 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....

  9. 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...

  10. Immigrants and health care: sources of vulnerability.

    Science.gov (United States)

    Derose, Kathryn Pitkin; Escarce, José J; Lurie, Nicole

    2007-01-01

    Immigrants have been identified as a vulnerable population, but there is heterogeneity in the degree to which they are vulnerable to inadequate health care. Here we examine the factors that affect immigrants' vulnerability, including socioeconomic background; immigration status; limited English proficiency; federal, state, and local policies on access to publicly funded health care; residential location; and stigma and marginalization. We find that, overall, immigrants have lower rates of health insurance, use less health care, and receive lower quality of care than U.S.-born populations; however, there are differences among subgroups. We conclude with policy options for addressing immigrants' vulnerabilities.

  11. Illegal immigration: a supply side analysis.

    Science.gov (United States)

    Bandyopadhyay, S; Bandyopadhyay, S C

    1998-12-01

    "This paper analyzes the supply-side determinants of illegal immigration using a three-sector general equilibrium model of the source country. Agricultural liberalization raises illegal immigration while liberalization of the high tech sector reduces it. In contrast, capital mobility in the source country renders trade policy ineffective for controlling illegal immigration. Paradoxically, increased enforcement (by the host country) may raise source country unskilled wages, although illegal immigration falls. Finally, under capital mobility, a rise in the source country restrictions on capital inflow raises the level of illegal immigration and reduces the effectiveness of border enforcement efforts by the host country." excerpt

  12. 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.

  13. Immigration Facts on Foreign Students

    Science.gov (United States)

    Ruiz, Neil G.

    2013-01-01

    U.S. policymakers have put forth various immigration reform proposals to improve retention of foreign students obtaining advanced degrees in science, technology, engineering, and mathematics (STEM) from American universities. These students are considered particularly desirable because they, like their American counterparts, offer the types of…

  14. Immigrant Workers and Farm Performance

    DEFF Research Database (Denmark)

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

    2013-01-01

    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...

  15. Senegalese Immigrant Entrepreneurial Entanglements and ...

    African Journals Online (AJOL)

    Senegalese entrepreneurship in South Africa is a typical example of how entrepreneurial entanglements are beginning to pose huge challenges to the theorization and understanding of modern African forms of business. This group of immigrant entrepreneurs finds it difficult to separate the use of charms and magic in the ...

  16. Telomerase expression is sufficient for chromosomal integrity in cells lacking p53 dependent G1 checkpoint function

    Directory of Open Access Journals (Sweden)

    Simpson Dennis A

    2005-10-01

    Full Text Available Abstract Background Secondary cultures of human fibroblasts display a finite lifespan ending at senescence. Loss of p53 function by mutation or viral oncogene expression bypasses senescence, allowing cell division to continue for an additional 10 – 20 doublings. During this time chromosomal aberrations seen in mitotic cells increase while DNA damage and decatenation checkpoint functions in G2 cells decrease. Methods To explore this complex interplay between chromosomal instability and checkpoint dysfunction, human fibroblast lines were derived that expressed HPV16E6 oncoprotein or dominant-negative alleles of p53 (A143V and H179Q with or without the catalytic subunit of telomerase. Results Cells with normal p53 function displayed 86 – 93% G1 arrest after exposure to 1.5 Gy ionizing radiation (IR. Expression of HPV16E6 or p53-H179Q severely attenuated G1 checkpoint function (3 – 20% arrest while p53-A143V expression induced intermediate attenuation (55 – 57% arrest irrespective of telomerase expression. All cell lines, regardless of telomerase expression or p53 status, exhibited a normal DNA damage G2 checkpoint response following exposure to 1.5 Gy IR prior to the senescence checkpoint. As telomerase-negative cells bypassed senescence, the frequencies of chromosomal aberrations increased generally congruent with attenuation of G2 checkpoint function. Telomerase expression allowed cells with defective p53 function to grow >175 doublings without chromosomal aberrations or attenuation of G2 checkpoint function. Conclusion Thus, chromosomal instability in cells with defective p53 function appears to depend upon telomere erosion not loss of the DNA damage induced G1 checkpoint.

  17. 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.

  18. Severe acute interstitial nephritis after combination immune-checkpoint inhibitor therapy for metastatic melanoma.

    Science.gov (United States)

    Murakami, Naoka; Borges, Thiago J; Yamashita, Michifumi; Riella, Leonardo V

    2016-06-01

    Immune-checkpoint inhibitors are emerging as revolutionary drugs for certain malignancies. However, blocking the co-inhibitory signals may lead to immune-related adverse events, mainly in the spectrum of autoimmune diseases including colitis, endocrinopathies and nephritis. Here, we report a case of a 75-year-old man with metastatic malignant melanoma treated with a combination of nivolumab (anti-PD1-antibody) and ipilimumab (anti-CTLA-4 antibody) who developed systemic rash along with severe acute tubulointerstitial nephritis after two doses of combination therapy. Kidney biopsy and peripheral blood immune profile revealed highly proliferative and cytotoxic T cell features. Herein, we discuss the pathophysiology and management of immune checkpoint blockade-related adverse events.

  19. 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.

  20. 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.

  1. Coupling of Human DNA Excision Repair and the DNA Damage Checkpoint in a Defined in Vitro System*

    Science.gov (United States)

    Lindsey-Boltz, Laura A.; Kemp, Michael G.; Reardon, Joyce T.; DeRocco, Vanessa; Iyer, Ravi R.; Modrich, Paul; Sancar, Aziz

    2014-01-01

    DNA repair and DNA damage checkpoints work in concert to help maintain genomic integrity. In vivo data suggest that these two global responses to DNA damage are coupled. It has been proposed that the canonical 30 nucleotide single-stranded DNA gap generated by nucleotide excision repair is the signal that activates the ATR-mediated DNA damage checkpoint response and that the signal is enhanced by gap enlargement by EXO1 (exonuclease 1) 5′ to 3′ exonuclease activity. Here we have used purified core nucleotide excision repair factors (RPA, XPA, XPC, TFIIH, XPG, and XPF-ERCC1), core DNA damage checkpoint proteins (ATR-ATRIP, TopBP1, RPA), and DNA damaged by a UV-mimetic agent to analyze the basic steps of DNA damage checkpoint response in a biochemically defined system. We find that checkpoint signaling as measured by phosphorylation of target proteins by the ATR kinase requires enlargement of the excision gap generated by the excision repair system by the 5′ to 3′ exonuclease activity of EXO1. We conclude that, in addition to damaged DNA, RPA, XPA, XPC, TFIIH, XPG, XPF-ERCC1, ATR-ATRIP, TopBP1, and EXO1 constitute the minimum essential set of factors for ATR-mediated DNA damage checkpoint response. PMID:24403078

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

    Energy Technology Data Exchange (ETDEWEB)

    Fukumoto, Yasunori, E-mail: fukumoto@faculty.chiba-u.jp; Kuki, Kazumasa; Morii, Mariko; Miura, Takahito; Honda, Takuya; Ishibashi, Kenichi; Hasegawa, Hitomi; Kubota, Sho; Ide, Yudai; Yamaguchi, Noritaka; Nakayama, Yuji; Yamaguchi, Naoto, E-mail: nyama@faculty.chiba-u.jp

    2014-09-26

    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.

  3. 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.

  4. 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

  5. Characterization of Spindle Checkpoint Kinase Mps1 Reveals Domain with Functional and Structural Similarities to Tetratricopeptide Repeat Motifs of Bub1 and BubR1 Checkpoint Kinases*

    Science.gov (United States)

    Lee, Semin; Thebault, Philippe; Freschi, Luca; Beaufils, Sylvie; Blundell, Tom L.; Landry, Christian R.; Bolanos-Garcia, Victor M.; Elowe, Sabine

    2012-01-01

    Kinetochore targeting of the mitotic kinases Bub1, BubR1, and Mps1 has been implicated in efficient execution of their functions in the spindle checkpoint, the self-monitoring system of the eukaryotic cell cycle that ensures chromosome segregation occurs with high fidelity. In all three kinases, kinetochore docking is mediated by the N-terminal region of the protein. Deletions within this region result in checkpoint failure and chromosome segregation defects. Here, we use an interdisciplinary approach that includes biophysical, biochemical, cell biological, and bioinformatics methods to study the N-terminal region of human Mps1. We report the identification of a tandem repeat of the tetratricopeptide repeat (TPR) motif in the N-terminal kinetochore binding region of Mps1, with close homology to the tandem TPR motif of Bub1 and BubR1. Phylogenetic analysis indicates that TPR Mps1 was acquired after the split between deutorostomes and protostomes, as it is distinguishable in chordates and echinoderms. Overexpression of TPR Mps1 resulted in decreased efficiency of both chromosome alignment and mitotic arrest, likely through displacement of endogenous Mps1 from the kinetochore and decreased Mps1 catalytic activity. Taken together, our multidisciplinary strategy provides new insights into the evolution, structural organization, and function of Mps1 N-terminal region. PMID:22187426

  6. Severe acute interstitial nephritis after combination immune-checkpoint inhibitor therapy for metastatic melanoma

    OpenAIRE

    Murakami, Naoka; Borges, Thiago J.; Yamashita, Michifumi; Riella, Leonardo V.

    2016-01-01

    Immune-checkpoint inhibitors are emerging as revolutionary drugs for certain malignancies. However, blocking the co-inhibitory signals may lead to immune-related adverse events, mainly in the spectrum of autoimmune diseases including colitis, endocrinopathies and nephritis. Here, we report a case of a 75-year-old man with metastatic malignant melanoma treated with a combination of nivolumab (anti-PD1-antibody) and ipilimumab (anti-CTLA-4 antibody) who developed systemic rash along with severe...

  7. NEK11 regulates CDC25A degradation and the IR-induced G2/M checkpoint

    DEFF Research Database (Denmark)

    Melixetian, M.; Helin, K.; Klein, D.K.

    2009-01-01

    new genes involved in the G2/M checkpoint we performed a large-scale short hairpin RNA (shRNA) library screen. We show that NIMA (never in mitosis gene A)-related kinase 11 (NEK11) is required for DNA damage-induced G2/M arrest. Depletion of NEK11 prevents proteasome-dependent degradation of CDC25A...... that genetic mutations in NEK11 may contribute to the development of human cancer....

  8. 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.

  9. 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

  10. Angiopoietin-2 as a biomarker and target for immune checkpoint therapy

    Science.gov (United States)

    Wu, Xinqi; Giobbie-Hurder, Anita; Liao, Xiaoyun; Connelly, Courtney; Connolly, Erin M.; Li, Jingjing; Manos, Michael P.; Lawrence, Donald; McDermott, David; Severgnini, Mariano; Zhou, Jun; Gjini, Evisa; Lako, Ana; Lipschitz, Mikel; Pak, Christine J.; Abdelrahman, Sara; Rodig, Scott; Hodi, F. Stephen

    2016-01-01

    Immune checkpoint therapies targeting CTLA-4 and PD-1 have proven effective in cancer treatment. However, the identification of biomarkers for predicting clinical outcomes and mechanisms to overcome resistance remain as critical needs. Angiogenesis is increasingly appreciated as an immune modulator with potential for combinatorial use with checkpoint blockade. Angiopoietin-2 (ANGPT2) is an immune target in patients and is involved in resistance to anti-VEGF treatment with the monoclonal antibody bevacizumab. We investigated the predictive and prognostic value of circulating ANGPT2 in metastatic melanoma patients receiving immune checkpoint therapy. High pretreatment serum ANGPT2 was associated with reduced overall survival in CTLA-4 and PD-1 blockade-treated patients. These treatments also increased serum ANGPT2 in many patients early after treatment initiation, whereas ipilimumab plus bevacizumab treatment decreased serum concentrations. ANGPT2 increases were associated with reduced response and/or overall survival. Ipilimumab increased, and ipilimumab plus bevacizumab decreased, tumor vascular ANGPT2 expression in a subset of patients, which was associated with increased and decreased tumor infiltration by CD68+ and CD163+ macrophages, respectively. In vitro, bevacizumab blocked VEGF-induced ANGPT2 expression in tumor-associated endothelial cells, whereas ANGPT2 increased PD-L1 expression on M2-polarized macrophages. Treatments elicited long-lasting and functional antibody responses to ANGPT2 in a subset of patients receiving clinical benefit. Our findings suggest that serum ANGPT2 may be considered as a predictive and prognostic biomarker for immune checkpoint therapy and may contribute to treatment resistance via increasing proangiogenic and immunosuppressive activities in the tumor microenvironment. Targeting ANGPT2 provides a rational combinatorial approach to improve the efficacy of immune therapy. PMID:28003187

  11. 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.

  12. 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...

  13. 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.

  14. 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.

  15. 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

  16. 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.

  17. 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)

  18. 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.

  19. Fear of Immigration Enforcement Among Older Latino Immigrants in the United States.

    Science.gov (United States)

    Rodriguez, Nestor; Paredes, Cristian L; Hagan, Jacqueline

    2017-06-01

    The passage of the 1996 Illegal Immigration Reform and Immigrant Responsibility Act (IIRIRA) and other subsequent restrictive immigration policies have created fear among Latino immigrants. This study examines whether fear of immigration enforcement is socially significant among older (50+ years) foreign-born Latino individuals in the United States without citizenship or permanent residence, and whether disapproval of immigrant enforcement policies is directly associated with fear of immigration enforcement among this older population. Data used in the analysis come from 2007, 2008, 2010, and 2013 national Latino surveys conducted by the Pew Research Center. Cross-sectional regression models are used to estimate the probabilities of fearing immigration enforcement in the Latino samples, as well as to examine the association between disapproval and fear of immigration enforcement. The study finds that the predicted probabilities of fearing immigration enforcement among foreign-born individuals aged 50 and over without citizenship or permanent residence are not negligible. Moreover, the study finds evidence of a direct association between the disapproval of enforcement measures and fear of immigration enforcement. Restrictive immigration measures have implications for conditions of fear and other stressors affecting the well-being of older immigrants.

  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. Do immigrants screened for skills do better than family reunification immigrants?

    Science.gov (United States)

    Jasso, G; Rosenzweig, M R

    1995-01-01

    "It is sometimes thought that immigrants [to the United States] who are screened for occupational skills are likely to become more productive Americans than immigrants who gain admission on the basis of family ties to native-born U.S. citizens or to previous immigrants. However, the expected differential may be small or nonexistent because: 1) kinship immigrants have access to family networks; 2) whereas employers may screen for short-term productivity, family members may screen for long-term productivity; and 3) native-born U.S citizens who sponsor spouses may be particularly adept at screening for long-term success. Longitudinal data on the 1977 immigrant cohort is used to compare initial and longer-term occupational outcomes among employment and kinship immigrants. Results indicate a narrowing of the differential, due both to higher rates of occupational downgrading among employment immigrants and of occupational upgrading among kinship immigrants." excerpt

  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. Circulation of immigrants to Hungary

    OpenAIRE

    Sándor Illés

    2015-01-01

    We measure the demographic patterns associated with international circular migration. Firstly, we define the circulation within the conceptual framework of transnationalism. Secondly, we create macro-scale data bank on long-term international circular migrants based on an original statistical method. Thirdly, we seek to gain further insight into the composition of international circular immigrants by gender, age, and family status. Conclusions indicate the need for future research.

  5. Venezuela: illegal immigration from Colombia.

    Science.gov (United States)

    Pellegrino, A

    1984-01-01

    The influx of illegal Colombian immigrants into Venezuela is studied using data from a variety of sources, including the 1971 census and several studies conducted in 1979-1980. The author examines the origins and destinations of migrants; age, sex, educational status, and occupational data; reasons for migration; and geographic distribution of the migrating population. Tables from Venezuela's General Foreign-Born Register of December 1980 are presented in an appendix.

  6. Risk of eating disorders in immigrant populations

    OpenAIRE

    Mustelin, L.; Hedman, A.; Thornton, L.M.; Kuja-Halkola, R.; Keski-Rahkonen, A.; Cantor-Graae, E.; Almqvist, C.; Lichtenstein, P.; Mortensen, P.B.; Böcker Pedersen, C.; Bulik, C.M.

    2017-01-01

    Objective: 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 differ from native-born Danes and Swedes. Method: 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 d...

  7. The Acceleration of Immigrant Unhealthy Assimilation

    OpenAIRE

    Giuntella, Osea; Stella, Luca

    2016-01-01

    It is well-known that immigrants tend to be healthier than US natives and that this advantage erodes with time spent in the US. However, we know less about the heterogeneity of these trajectories among arrival cohorts. Recent studies have shown that later arrival cohorts of immigrants have lower entry wages and experience less economic assimilation. In this paper, we investigate whether similar cohort effects can be observed in the weight assimilation of immigrants in the US. Focusing on obes...

  8. 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…

  9. 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

  10. 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…

  11. 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.

  12. Immigrant Narratives: Power, Difference, and Representation in Young-Adult Novels with Immigrant Protagonists

    Science.gov (United States)

    Clifford, Elizabeth; Kalyanpur, Maya

    2011-01-01

    As of 2008, about 23% of children in the United States were immigrants or the children of immigrants. This paper examines how immigrants are portrayed in books aimed at teenagers. From a sample of 20 young-adult novels we look at the demographics of both protagonist and author and examine how three main themes are addressed: (1) experiences prior…

  13. The Effect of Immigrant Concentration in Schools on Native and Immigrant Children's Reading and Math Skills

    Science.gov (United States)

    Jensen, Peter; Rasmussen, Astrid Wurtz

    2011-01-01

    Using a unique and very rich PISA dataset from Denmark, we show that the immigrant concentration in the school influences reading and math skills for both immigrant children and native children. Overall, children in schools with a high immigrant concentration score lower on reading and math test scores. The negative effects associated with…

  14. Immigration and the Interplay among Citizenship, Identity and Career: The Case of Ethiopian Immigration to Israel

    Science.gov (United States)

    Flum, Hanoch; Cinamon, Rachel Gali

    2011-01-01

    Migration is a common phenomenon of the globalization era. In this article we explore the interplay of three foundational concepts in the migration experiences of Ethiopian Jewish immigrants in Israel: citizenship, identity and career. Through our analysis we examine the multiple layers of being an immigrant citizen. Following immigration, as…

  15. Trade Unions, immigration and immigrants in Europe revisited: Unions’ attitudes and actions under new conditions

    NARCIS (Netherlands)

    Marino, S.; Penninx, R.; Roosblad, J.

    2015-01-01

    This paper revisits the comparative approach used by Penninx and Roosblad (Trade Unions, Immigration and Immigrants in Europe, 1960-1993. New York: Berghahn Books) to study trade unions’ attitudes and actions in relation to immigrant workers in seven Western European countries. It reassesses that

  16. 78 FR 31398 - Visas: Documentation of Immigrants Under the Immigration and Nationality Act, as Amended

    Science.gov (United States)

    2013-05-24

    ... receives evidence--that the alien is within the criteria set forth in paragraph (b) of this section... method of recording an alien's entitlement to an immigrant visa classification. Due to the availability... recording an alien's entitlement to an immigrant visa classification. Section 203(e)(3) of the Immigration...

  17. 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…

  18. The Europeanisation of immigration politics

    Directory of Open Access Journals (Sweden)

    Adrian Favell

    1998-12-01

    Full Text Available With the 1996-7 IGC and signing of the Amsterdam Treaty, immigration has moved towards the top of the EU policy agenda. This paper offers an overview of developments on immigration, asylum and citizenship. It goes on to develop a sociological approach to Europeanisation, which identifies the principle actors and organisations which constitute the emerging ‘political field’ of immigration at the EU level. In particular, it discusses in detail the growing presence of NGOs in Brussels, and their strategies for influencing EU policy making. It also relates the success of these ‘transnational’ organisations to other forms of transnational cooperation between networks of European police and security experts, and between region and city networks. To understand in sociological terms the specific forms of empowerment enabled to certain groups by European integration, it is necessary to show how successful actors in the European circles have created new forms of social and cultural ‘capital’ beyond the nation state.

  19. 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.

  20. 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.

  1. 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...

  2. 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.

  3. US immigration policy at a crossroads

    OpenAIRE

    Duleep, Harriet Orcutt

    2013-01-01

    Two issues have taken center stage in the recent debates about U.S. immigration policy: one, illegal immigration and more generally the entrance of poorly educated individuals into the U.S. economy and two, whether the U.S. should continue its family-based admissions system or move towards a skills-based system. This paper analyzes these issues culling evidence from the history of U.S. immigration policy, the experiences of different types of U.S. immigrants, and cross-national comparisons.

  4. America's post-war immigration policy.

    Science.gov (United States)

    Batterson, R F

    1984-01-01

    This article provides a historical perspective on immigration policy in the US after World War II and assesses the present situation. US immigration and refugee policy has undergone significant change since World War II. The McCarran-Walter Act of 1952, which instituted a system of proportional quotas based on national origins, was discarded in 1965 following years of criticism that it discriminated against nonwhites. Third World immigrants, especially from Asia and the Americas, have benefited from the immigration laws. However, the problems resulting from unrestricted and undifferentiated immigration are now becoming apparent, even to liberal critics of previous national origins policies. During the 1970s, there was a 61% increase in the number of Mexican nationals in the US and Mexicans currently comprise over 20% of the population in 40 Congressional districts in 8 states. 83.3% of legal immigrants, and all illegal immigrants, are of non-European descent--a fact that may retard their assimilation and intensify ethnic tensions. There is a danger that the concept of national borders may become superfluous. The theoreticval liberalism of the 1950s and 1960s is, in the 1970s, being confronted with the reality of large numbers of immigrants unable and unwilling to be absorbed into a previously European-dominated country. It is concluded that the enforced application of the concept of equality in matters of immigration has not been the panacea that its liberal proponents envisioned.

  5. 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...

  6. 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...

  7. 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...

  8. [French immigration policy at a turning point?].

    Science.gov (United States)

    Wihtol De Wenden, C

    1995-01-01

    The author examines the changes to French immigration law adopted in 1993 in the light of current trends and pressures affecting migration to France. The focus is on the changes in the rules concerning the acquisition of French nationality, and the assimilation of existing immigrants from developing countries. The difficulties of resolving such problems at the national level while migration regulations are being developed at the European Community level are noted. Problems involving the control of the nation's borders, illegal immigration, and the growing demand for political asylum are also discussed. The author raises the possibility that immigration could be better managed in light of current labor market conditions in France.

  9. Immigration Policy in the United States: Future Prospects for the Immigration Reform and Control Act of 1986. Program for Resarch on Immigration Policy.

    Science.gov (United States)

    Espenshade, Thomas J.; And Others

    Immigration to the United States has fluctuated considerably over the course of the nation's history and has elicited various policy responses at different times. In recent years, concern about undocumented, illegal immigration has given rise to efforts to reform immigration law. The Immigration Reform and Control Act (IRCA) of 1986 was intended…

  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. American immigration policy, Chinese immigration, and Chinese concentration in New York City.

    Science.gov (United States)

    Chow, C S

    1985-07-01

    This article explores the relationship between US immigration laws, Chinese immigrants' initial choices of residences and occupations in New York City, and the recent expansion of New York's Chinatown. Data were obtained from a questionnaire administered to 121 Chinese immigrants in New York in 1980. It was hypothesized that a high degree of immigrant concentration in areas such as Chinatown is a result of migration policies that favor chain migration. During the period of time (1943-65) when Chinese immigration was severely restricted by the Chinese Exclusion Act and a quota system, the Chinese population in New York remained small. By 1980, however, the Chinese population in New York City had grown to 124,764 (1.8% of the city's population). This was largely a result of the 1965 Immigration Act, which allows an annual quota of 20,000 immigrants per country and gives preference to family members of American citizens and permanent residents. Support for the hypothesis that the current immigration law encourages chain migration was provided by the finding that the majority of Chinese immigrants surveyed immigrated under the sponsorship of close relatives (53.7%) or as children with parents (13.2%). 53.4% had their initial residence arranged for or provided by relatives, and another 33.1% by friends--a pattern that has contributed to the expansion of Chinatown. To minimize the risk of having their applications for the immigration of family members declined, Chinese in New York refrain from seeking public assistance and take whatever jobs are available. 55% of immigrants surveyed obtained work in restaurants or garment factories in Chinatown, further sustaining a Chinese enclave. It is concluded that a theoretical perspective that emphasizes the link between migration policy and immigrants' choices regarding residence and occupation has more utility than hypotheses that assert a causal relationship between racial discrimination against minorities, nonassimilation of

  12. 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

  13. „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

  14. 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.

  15. Bullying among immigrant and non-immigrant early adolescents: School- and student-level effects.

    Science.gov (United States)

    Vitoroulis, Irene; Georgiades, Katholiki

    2017-12-01

    We examined the association between school immigrant concentration and bullying among immigrant and non-immigrant early adolescents, and identified potential explanatory factors. First generation immigrant students had reduced odds of victimization and perpetration in schools with high (20-60%), compared to low, levels of immigrant concentration. Second generation immigrant students had reduced odds of ethnic/racial victimization in moderately concentrated schools; while non-immigrants had increased odds in the same schools. Non-white students had increased odds of ethnic/racial victimization compared to White students. While students' sense of school belonging and perceived teacher cultural sensitivity were negatively associated with bullying, they did not account for the differential associations noted above. Results demonstrate the importance of immigrant density as a protective school characteristic for immigrant and ethnic minority youth. Additional social processes operating in schools that may explain bullying behaviors among immigrant and non-immigrant youth should be explored to inform programs for promoting inclusion in schools. Copyright © 2017 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. Bub3 is a spindle assembly checkpoint protein regulating chromosome segregation during mouse oocyte meiosis.

    Directory of Open Access Journals (Sweden)

    Mo Li

    Full Text Available In mitosis, the spindle assembly checkpoint (SAC prevents anaphase onset until all chromosomes have been attached to the spindle microtubules and aligned correctly at the equatorial metaphase plate. The major checkpoint proteins in mitosis consist of mitotic arrest-deficient (Mad1-3, budding uninhibited by benzimidazole (Bub1, Bub3, and monopolar spindle 1(Mps1. During meiosis, for the formation of a haploid gamete, two consecutive rounds of chromosome segregation occur with only one round of DNA replication. To pull homologous chromosomes to opposite spindle poles during meiosis I, both sister kinetochores of a homologue must face toward the same pole which is very different from mitosis and meiosis II. As a core member of checkpoint proteins, the individual role of Bub3 in mammalian oocyte meiosis is unclear. In this study, using overexpression and RNA interference (RNAi approaches, we analyzed the role of Bub3 in mouse oocyte meiosis. Our data showed that overexpressed Bub3 inhibited meiotic metaphase-anaphase transition by preventing homologous chromosome and sister chromatid segregations in meiosis I and II, respectively. Misaligned chromosomes, abnormal polar body and double polar bodies were observed in Bub3 knock-down oocytes, causing aneuploidy. Furthermore, through cold treatment combined with Bub3 overexpression, we found that overexpressed Bub3 affected the attachments of microtubules and kinetochores during metaphase-anaphase transition. We propose that as a member of SAC, Bub3 is required for regulation of both meiosis I and II, and is potentially involved in kinetochore-microtubule attachment in mammalian oocytes.

  1. 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

  2. Measuring immigration policies: preliminary evidence from IMPALA

    NARCIS (Netherlands)

    Beine, M.; Burgoon, B.M.; Crock, M.; Gest, J.; Hiscox, M.; McGovern, P.; Rapoport, H.; Thielemann, E.

    2015-01-01

    This article presents the methods and preliminary findings from IMPALA, a database that systematically measures the character and stringency of immigration policies. Based on a selection of data for six pilot countries between 1990 and 2008, we document the variation of immigration policies across

  3. Immigrant Students and the Obstacles to Achievement

    Science.gov (United States)

    Stratton, Tamiko; Pang, Valerie Ooka; Madueno, Marcelina; Park, Cynthia D.; Atlas, Miriam; Page, Cindy; Oliger, Jennifer

    2009-01-01

    This article describes composites of actual students, but examples of hardworking immigrant students and their families can be found in every state. Many young immigrants are negotiating their place in society. They believe in the American Dream and struggle with issues of poverty, language, cultural assimilation, and the desire to further their…

  4. 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.

  5. 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…

  6. Effectiveness and costeffectiveness of screening immigrants ...

    African Journals Online (AJOL)

    veloped 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 through general practices, hospitals, chest-clinics and emergency departments. Evidence of the effectiveness and cost effectiveness of ...

  7. 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…

  8. The recent evolution of immigration in Venezuela.

    Science.gov (United States)

    Pellegrino, A

    1985-09-01

    Recent trends in immigration to Venezuela are reviewed. Data are from official sources, including the 1981 census and a 1981 survey of migrants. An analysis of migrants by major country or region of origin is presented that includes consideration of geographic distribution, migrant characteristics, and the characteristics of illegal immigration.

  9. 8 CFR 1240.1 - Immigration judges.

    Science.gov (United States)

    2010-01-01

    ... REGULATIONS PROCEEDINGS TO DETERMINE REMOVABILITY OF ALIENS IN THE UNITED STATES Removal Proceedings § 1240.1 Immigration judges. (a) Authority. (1) In any removal proceeding pursuant to section 240 of the Act, the... 8 Aliens and Nationality 1 2010-01-01 2010-01-01 false Immigration judges. 1240.1 Section 1240.1...

  10. LGBT Adult Immigrants in the United States

    OpenAIRE

    Gates, Gary J.

    2013-01-01

    There are approximately 267,000 LGBT-identified individuals among the adult undocumented immigrant population and an estimated 637,000 LGBT-identified individuals among the adult documented immigrant population. The report finds that approximately 71 percent of undocumented LGBT adults are Hispanic and 15 percent of undocumented LGBT adults are Asian or Pacific Islander.

  11. Do Immigrants Affect Firm-Specific Wages?

    DEFF Research Database (Denmark)

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

    2012-01-01

    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...

  12. The Impact of Growing and Illegal Immigration.

    Science.gov (United States)

    Taylor, William L.

    1980-01-01

    Discusses the tenuous status of illegal immigrants in the United States, emphasizing the implications of the presence of a large class of people so alienated from the social system. Holds that undocumented immigrants should be permitted to become productive members of society. (Author/GC)

  13. State Legislatures Debate Tuition for Illegal Immigrants

    Science.gov (United States)

    Keller, Josh

    2007-01-01

    With plans for a sweeping federal immigration bill stuck in Congress, Arizona and a growing number of states have decided to try to deal with the in-state-tuition issue themselves. This spring lawmakers in at least 22 states have already considered or are debating legislation concerning in-state tuition to illegal immigrants. In about half of…

  14. Essays on Legal and Illegal Immigration.

    Science.gov (United States)

    Pozo, Susan, Ed.

    Major issues of the debate that led to the passage of an immigration reform bill are discussed and analyzed in this collection of six papers that were delivered as public lectures at Western Michigan University during the 1984-85 academic year. The essays reflect a broad range of views on the effects of immigration on the United States economy and…

  15. 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...

  16. Immigration Laws Are Education Laws Too.

    Science.gov (United States)

    Stewart, David

    1994-01-01

    The 1965 Immigration Act has significantly influenced American institutions and agencies. This act, which focused on family reunification and desired occupational skills instead of racial origin, has resulted in a massive increase of immigrant students from Asia and Latin America without increased funding to educate and assimilate them. Reduction…

  17. 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.

  18. Immigrants, English Ability and the Digital Divide

    Science.gov (United States)

    Ono, Hiroshi; Zavodny, Madeline

    2008-01-01

    This study examines the extent and causes of inequalities in information technology ownership and use between natives and immigrants in the United States, with particular focus on the role of English ability. The results indicate that, during the period 1997-2003, immigrants were significantly less likely to have access to or use a computer and…

  19. 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...

  20. 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…

  1. Income of immigrants and their return

    NARCIS (Netherlands)

    Bijwaard, G.E.

    2015-01-01

    The majority of immigrants stay only temporarily in the host country. When many migrations are temporary, it is important to know who leaves and who stays, and why. The key questions for the host country are whether immigrants are net contributors to the welfare system and whether migrants

  2. 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,…

  3. David Miller on Immigration Policy and Nationality

    DEFF Research Database (Denmark)

    Lægaard, Sune

    2007-01-01

    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. A checkpoint control orchestrates the replication of the two chromosomes of Vibrio cholerae

    DEFF Research Database (Denmark)

    Val, Marie-Eve; Marbouty, Martial; Martins, Francisco de Lemos

    2016-01-01

    cycle and coordinated in such a way that replication termination occurs at the same time. However, the mechanism coordinating this synchrony remains speculative. We investigated this mechanism and revealed that initiation of Chr2 replication is triggered by the replication of a 150-bp locus positioned...... on Chr1, called crtS. This crtS replication–mediated Chr2 replication initiation mechanism explains how the two chromosomes communicate to coordinate their replication. Our study reveals a new checkpoint control mechanism in bacteria, and highlights possible functional interactions mediated by contacts...

  5. Dpb11/TopBP1 contributes to genomicstability via homologous recombinationand checkpoint signaling

    DEFF Research Database (Denmark)

    Germann, Susanne Manuela

    for recruitment. Also, the chicken homologue TopBP1 colocalizes with RPA1 as well as Rad51 when DNA damage is induced. Previously, dpb11 mutants have been shown to be sensitive to DNA-damaging agents that cause DSBs, DNA alkylation and stalled replication forks. Interestingly, we found the point mutants dpb11-PF...... and dpb11-R being exclusively sensitive to DSB-inducing agents, suggesting a separation of function between DNA repair and replication. These two mutants interact significantly less with members of the 9-1-1 complex or the Rad24 clamp loader in a two-hybrid analysis, suggesting a defect in checkpoint...

  6. 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.)

  7. ANCHR mediates Aurora-B-dependent abscission checkpoint control through retention of VPS4

    DEFF Research Database (Denmark)

    Thoresen, Sigrid B; Campsteijn, Coen; Vietri, Marina

    2014-01-01

    of the ESCRT machinery, the ATPase VPS4. In concert with CHMP4C, ANCHR associates with VPS4 at the midbody ring following DNA segregation defects to control abscission timing and prevent multinucleation in an Aurora-B-dependent manner. This association prevents VPS4 relocalization to the abscission zone...... and is relieved following inactivation of Aurora B to allow abscission. We propose that the abscission checkpoint is mediated by ANCHR and CHMP4C through retention of VPS4 at the midbody ring....

  8. 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.

  9. Human Embryonic Stem Cells Are Capable of Executing G1/S Checkpoint Activation

    Czech Academy of Sciences Publication Activity Database

    Bárta, Tomáš; Vinarský, Vladimír; Holubcová, Z.; Doležalová, Dáša; Verner, J.; Pospíšilová, Š.; Dvořák, Petr; Hampl, Aleš

    2010-01-01

    Roč. 28, č. 7 (2010), s. 1143-1152 ISSN 1066-5099 Grant - others:GA MŠk(CZ) 1M0538; GA MZd(CZ) NS10439; GA MŠk(CZ) MUNIE/E/0118/2009; EC FP6(XE) LSHG-CT-2006-018739 Program:1M Institutional research plan: CEZ:AV0Z50390512; CEZ:AV0Z50390703 Keywords : human embryonic stem cells * DNA damage * checkpoint activation Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 7.871, year: 2010

  10. 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

  11. 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

  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. 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.

  14. 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

  15. Language Barriers and Immigrant Health.

    Science.gov (United States)

    Clarke, Andrew; Isphording, Ingo E

    2017-06-01

    We study the impact of language deficiency on the health status of childhood migrants to Australia. Our identification strategy relies on a quasi-experiment comparing immigrants arriving at different ages and from different linguistic origins. In the presence of considerable non-classical measurement error in self-reported language proficiency, our results provide lower and upper bounds for a strong negative effect of English deficiency on health of between one half and a full standard deviation in the health score. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  16. The Caenorhabditis elegans WRN helicase promotes double-strand DNA break repair by mediating end resection and checkpoint activation.

    Science.gov (United States)

    Ryu, Jin-Sun; Koo, Hyeon-Sook

    2017-07-01

    The protein associated with Werner syndrome (WRN), is involved in DNA repair, checkpoint activation, and telomere maintenance. To better understand the involvement of WRN in double-strand DNA break (DSB) repair, we analyzed the combinatorial role of WRN-1, the Caenorhabditis elegans WRN helicase, in conjunction with EXO-1 and DNA-2 nucleases. We found that WRN-1 cooperates with DNA-2 to resect DSB ends in a pathway acting in parallel to EXO-1. The wrn-1 mutants show an aberrant accumulation of replication protein A (RPA) and RAD-51, and the same pattern of accumulation is also observed in checkpoint-defective strains. We conclude that WRN-1 plays a conserved role in the resection of DSB ends and mediates checkpoint signaling, thereby influencing levels of RPA and RAD-51. © 2017 Federation of European Biochemical Societies.

  17. G2/M-Phase Checkpoint Adaptation and Micronuclei Formation as Mechanisms That Contribute to Genomic Instability in Human Cells.

    Science.gov (United States)

    Kalsbeek, Danî; Golsteyn, Roy M

    2017-11-06

    One of the most common characteristics of cancer cells is genomic instability. Recent research has revealed that G2/M-phase checkpoint adaptation-entering mitosis with damaged DNA-contributes to genomic changes in experimental models. When cancer cells are treated with pharmacological concentrations of genotoxic agents, they undergo checkpoint adaptation; however, a small number of cells are able to survive and accumulate micronuclei. These micronuclei harbour damaged DNA, and are able to replicate and reincorporate their DNA into the main nucleus. Micronuclei are susceptible to chromothripsis, which is a phenomenon characterised by extensively rearranged chromosomes that reassemble from pulverized chromosomes in one cellular event. These processes contribute to genomic instability in cancer cells that survive a genotoxic anti-cancer treatment. This review provides insight into checkpoint adaptation and its connection to micronuclei and possibly chromothripsis. Knowledge about these mechanisms is needed to improve the poor cancer treatment outcomes that result from genomic instability.

  18. Integrating Immune Checkpoint Blockade with Anti-Neo/Mutated Antigens Reactivity to Increase the Clinical Outcome of Immunotherapy

    Directory of Open Access Journals (Sweden)

    Giorgio Parmiani

    2015-05-01

    Full Text Available Antibodies to immune checkpoints have entered the clinical arena and have been shown to provide a clinical benefit for metastatic melanoma and, possibly, for other tumors as well. In this review paper we summarize this therapeutic activity and underline the functional mechanisms that may be involved. Among them, we discuss the so far neglected role of tumor-associated antigens (TAAs deriving from tumor somatic mutations and summarize the results of recent trials showing the immunogenic strength of such TAAs which can be specifically targeted by T cells activated by immune checkpoint antibodies. Finally we discuss new immunotherapy approaches that involve the combination of self/shared- or neo-TAAs-based vaccines and immune checkpoint blockade antibodies, to increase the clinical response of metastatic melanoma patients.

  19. 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...... 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...

  20. 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.

  1. 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

  2. Optimal management of immune-related adverse events resulting from treatment with immune checkpoint inhibitors: a review and update.

    Science.gov (United States)

    Nagai, Hiroki; Muto, Manabu

    2018-03-07

    Over the last two decades, molecular-targeted agents have become mainstream treatment for many types of malignancies and have improved the overall survival of patients. However, most patients eventually develop resistance to these targeted therapies. Recently, immunotherapies such as immune checkpoint inhibitors have revolutionized the treatment paradigm for many types of malignancies. Immune checkpoint inhibitors have been approved for treatment of melanoma, non-small cell lung cancer, renal cell carcinoma, head and neck squamous cell carcinoma, Hodgkin's lymphoma, bladder cancer and gastric cancer. However, oncologists have been faced with immune-related adverse events caused by immune checkpoint inhibitors; these are generally mild but can be fatal in some cases. Because immune checkpoint inhibitors have distinct toxicity profiles from those of chemotherapy or targeted therapy, many oncologists are not familiar with the principles for optimal management of immune-related adverse events, which require early recognition and appropriate treatment without delay. To achieve this, oncologists must educate patients and health-care workers, develop checklists of appropriate tests for immune-related adverse events and collaborate closely with organ specialists. Clinical questions that remain include whether immune checkpoint inhibitors should be administered to patients with autoimmune disease and whether patients for whom immune-related adverse events lead to delays in immunotherapy should be retreated. In addition, the predicted use of combination immunotherapies in the near future means that oncologists will face a higher incidence and severity of immune-related adverse events. This review provides an overview of the optimal management of immune-related adverse events attributed to immune checkpoint inhibitors.

  3. Delineation of the role of chromatin assembly and the Rtt101Mms1 E3 ubiquitin ligase in DNA damage checkpoint recovery in budding yeast.

    Directory of Open Access Journals (Sweden)

    Li-Ting Diao

    Full Text Available The DNA damage checkpoint is activated in response to DNA double-strand breaks (DSBs. We had previously shown that chromatin assembly mediated by the histone chaperone Asf1 triggers inactivation of the DNA damage checkpoint in yeast after DSB repair, also called checkpoint recovery. Here we show that chromatin assembly factor 1 (CAF-1 also contributes to chromatin reassembly after DSB repair, explaining its role in checkpoint recovery. Towards understanding how chromatin assembly promotes checkpoint recovery, we find persistent presence of the damage sensors Ddc1 and Ddc2 after DSB repair in asf1 mutants. The genes encoding the E3 ubiquitin ligase complex Rtt101Mms1 are epistatic to ASF1 for survival following induction of a DSB, and Rtt101Mms1 are required for checkpoint recovery after DSB repair but not for chromatin assembly. By contrast, the Mms22 substrate adaptor that is degraded by Rtt101Mms1 is required for DSB repair per se. Deletion of MMS22 blocks loading of Rad51 at the DSB, while deletion of ASF1 or RTT101 leads to persistent Rad51 loading. We propose that checkpoint recovery is promoted by Rtt101Mms1-mediated ubiquitylation of Mms22 in order to halt Mms22-dependent loading of Rad51 onto double-stranded DNA after DSB repair, in concert with the chromatin assembly-mediated displacement of Rad51 and checkpoint sensors from the site of repair.

  4. Is the new immigration less skilled than the old?

    Science.gov (United States)

    Chiswick, B R

    1986-04-01

    This paper analyzes trends in the skills of immigrants to the US in the post-World War II period. Changes in the supply, demand, and institutional factors determining immigration are analyzed for their implications for immigrant skills. During the past 4 decades immigration has shifted from being predominantly European and Canadian in origin to being predominantly Asian and Latin American, and there have been changes in the criteria for rationing immigration visas. Immigrant skills can be analyzed within the context of a model of the supply of immigrants and the US demand for immigrants. Of the Asian immigrants subject to numerical limitation, the proportion who were occupational preference principals declined from 18.2% in 1970, to 11.9% in 1975, to 8.1% in 1981. A growing stock of the foreign-born population who are illegal aliens may lower immigrant quality; for low-skilled workers in neighboring low-income countries the economic incentives for illegal migration are very large. Immigrants from the UK have the highest annual earnings, with Canadian, other European, South Asian, East Asian, and other American immigrants having successively lower earnings. The Mexicans and the Vietnamese have the lowest earnings. Over the period 1950 to 1980, US immigration changed from primarily drawing immigrants from countries whose nationals have high relative earnings in the US primarily drawing immigrants from countries whose nationals do less well. Recent immigrants are less favorably selected on the basis of their level of schooling. The analysis of the relative earnings of immigrants during the 1970s using 3 data files shows there has been little change for white immigrants, an ambiguous pattern for Mexican immgrants, perhaps a small decline for Cuban immigrants, and a small rise for Asian immigrants. Overall, without returning to rationing by country of origin, public policy could raise immigrant skill levels by changing the balance between kinship and the individual

  5. The interplay among chromatin dynamics, cell cycle checkpoints and repair mechanisms modulates the cellular response to DNA damage.

    Science.gov (United States)

    Lazzaro, Federico; Giannattasio, Michele; Muzi-Falconi, Marco; Plevani, Paolo

    2007-06-01

    Cells are continuously under the assault of endogenous and exogenous genotoxic stress that challenges the integrity of DNA. To cope with such a formidable task cells have evolved surveillance mechanisms, known as checkpoints, and a variety of DNA repair systems responding to different types of DNA lesions. These lesions occur in the context of the chromatin structure and, as expected for all DNA transactions, the cellular response to DNA damage is going to be influenced by the chromatin enviroment. In this review, we will discuss recent studies implicating chromatin remodelling factors and histone modifications in the response to DNA double-strand breaks (DSBs) and in checkpoint activation in response to UV lesions.

  6. Distinct domains in Bub1 localize RZZ and BubR1 to kinetochores to regulate the checkpoint

    DEFF Research Database (Denmark)

    Zhang, Gang; Lischetti, Tiziana; Hayward, Daniel G

    2015-01-01

    The spindle assembly checkpoint (SAC) ensures proper chromosome segregation by delaying anaphase onset in response to unattached kinetochores. Checkpoint signalling requires the kinetochore localization of the Mad1-Mad2 complex that in more complex eukaryotes depends on the Rod-Zwilch-ZW10 (RZZ......) complex. The kinetochore protein Zwint has been proposed to be the kinetochore receptor for RZZ, but here we show that Bub1 and not Zwint is required for RZZ recruitment. We find that the middle region of Bub1 encompassing a domain essential for SAC signalling contributes to RZZ localization. In addition...

  7. The Spindle Assembly Checkpoint Is Not Essential for Viability of Human Cells with Genetically Lowered APC/C Activity

    DEFF Research Database (Denmark)

    Wild, Thomas; Larsen, Marie Sofie Yoo; Narita, Takeo

    2016-01-01

    The anaphase-promoting complex/cyclosome (APC/C) and the spindle assembly checkpoint (SAC), which inhibits the APC/C, are essential determinants of mitotic timing and faithful division of genetic material. Activation of the APC/C is known to depend on two APC/C-interacting E2 ubiquitin-conjugatin......The anaphase-promoting complex/cyclosome (APC/C) and the spindle assembly checkpoint (SAC), which inhibits the APC/C, are essential determinants of mitotic timing and faithful division of genetic material. Activation of the APC/C is known to depend on two APC/C-interacting E2 ubiquitin...

  8. Cytotoxic amounts of cisplatin induce either checkpoint adaptation or apoptosis in a concentration-dependent manner in cancer cells.

    Science.gov (United States)

    Swift, Lucy H; Golsteyn, Roy M

    2016-05-01

    Checkpoint adaptation (entry into mitosis with damaged DNA) is a process that links arrest at the G2/M cell cycle checkpoint and cell death in cancer cells. It is not known, however, whether cells treated with the genotoxic agent, cisplatin, undergo checkpoint adaptation or if checkpoint adaptation is a major pathway leading to cell death or not. Therefore, we investigated the relationship between treatment with cisplatin and cytotoxicity in cancer cells. Treatment of HT-29 human colorectal adenocarcinoma cells with cisplatin can induce cell death by one of two different mechanisms. Cells treated with a cytotoxic 30 μM amount of cisplatin died after undergoing checkpoint adaptation. Before dying, however, almost all treated cells were positive for histone γH2AX staining and contained high levels of cyclin B1. Rounded cells appeared that were positive for phospho-Ser10 histone H3, with low levels of phospho-Tyr15 cyclin-dependent kinase 1, high levels of cyclin-dependent kinase 1 activity, and checkpoint kinase 1 that was not phosphorylated on Ser345. These cells were in mitosis with damaged DNA. Strikingly, with 30 μM cisplatin, 81% of cells had entered mitosis before dying. By contrast, after treatment with 100 μM cisplatin, nearly all cells died but only 7% of cells had entered mitosis. Instead, these cells died by apoptosis; they were positive for annexin-V staining, contained cleaved caspase 3, cleaved caspase 9 and cleaved PARP and did not contain Mcl-1. Our data demonstrate that cancer cells treated with cisplatin can undergo one of two modes of cell death depending upon concentration used. These findings suggest that checkpoint adaptation is likely a primary pathway in genotoxic cell death at pharmacological concentrations of cisplatin. Checkpoint adaptation might be a common biochemical pathway taken by human cancer cells in response to pharmacologically relevant, cytotoxic amounts of damaged DNA. © 2016 Société Française des Microscopies and Soci

  9. 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...

  10. 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...

  11. 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...

  12. 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...

  13. 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…

  14. 8 CFR 1235.6 - Referral to immigration judge.

    Science.gov (United States)

    2010-01-01

    ... immigration judge may consider eligibility for withholding of removal pursuant to section 241(b)(3) of the Act... 8 Aliens and Nationality 1 2010-01-01 2010-01-01 false Referral to immigration judge. 1235.6... IMMIGRATION REGULATIONS INSPECTION OF PERSONS APPLYING FOR ADMISSION § 1235.6 Referral to immigration judge...

  15. Immigration Reform in Its First Year. CIS Paper 4.

    Science.gov (United States)

    North, David S.

    This document assesses the preliminary impact of the first year of the Immigration Reform and Control Act of 1986 (IRCA). The act had three primary goals: (1) to discourage illegal immigration into the United States and to encourage the departure of recent illegal immigrants; (2) to permit the legalization of illegal immigrants who have been in…

  16. Impact of Immigration on the School District Administrators.

    Science.gov (United States)

    Garza, Gonzalo

    Data on illegal immigration from Mexico into Texas provide accurate information on the impact of this immigration on the generally underfunded and understaffed border school districts in the state. Immigration and Naturalization Service statistics show 20 million illegal immigrants in the United States. A more scientific estimate is 4 million, 2.7…

  17. Framing Unauthorized Immigrants: The Effect of Labels on Evaluations

    NARCIS (Netherlands)

    Ommundsen, R.; van der Veer, C.G.; Larsen, K.S.; Eilertsen, D.E.

    2014-01-01

    In the U.S. media, unauthorized immigrants are often interchangeably referred to as "illegal aliens," "illegal immigrants," and undocumented immigrants." In spite of formal equivalence, these terms carry different connotations, but the effects of these labels on people's attitudes toward immigrants

  18. The New Immigration: Implications for Poverty and Public Assistance Utilization.

    Science.gov (United States)

    Jensen, Leif; Tienda, Marta

    1987-01-01

    Documents and explains immigrant-native born American trends and differentials in poverty and public assistance utilization from 1960-1980. Immigration over this period is characterized by increases in the following: (1) flow of immigration; (2) downward trend in immigrants entering under the family reunification provisions; (3) percentage…

  19. 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...

  20. 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

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

    OpenAIRE

    Abdurrahman Aydemir

    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.

  2. 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...

  3. 22 CFR 42.32 - Employment-based preference immigrants.

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Employment-based preference immigrants. 42.32 Section 42.32 Foreign Relations DEPARTMENT OF STATE VISAS VISAS: DOCUMENTATION OF IMMIGRANTS UNDER THE IMMIGRATION AND NATIONALITY ACT, AS AMENDED Immigrants Subject to Numerical Limitations § 42.32 Employment...

  4. 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...

  5. 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…

  6. Host-Pathogen Checkpoints and Population Bottlenecks in Persistent and Intracellular Uropathogenic E. coli Bladder Infection

    Science.gov (United States)

    Hannan, Thomas J.; Totsika, Makrina; Mansfield, Kylie J.; Moore, Kate H.; Schembri, Mark A.; Hultgren, Scott J.

    2013-01-01

    Bladder infections affect millions of people yearly, and recurrent symptomatic infections (cystitis) are very common. The rapid increase in infections caused by multi-drug resistant uropathogens threatens to make recurrent cystitis an increasingly troubling public health concern. Uropathogenic E. coli (UPEC) cause the vast majority of bladder infections. Upon entry into the lower urinary tract, UPEC face obstacles to colonization that constitute population bottlenecks, reducing diversity and selecting for fit clones. A critical mucosal barrier to bladder infection is the epithelium (urothelium). UPEC bypass this barrier when they invade urothelial cells and form intracellular bacterial communities (IBCs), a process which requires type 1 pili. IBCs are transient in nature, occurring primarily during acute infection. Chronic bladder infection is common and can be either latent, in the form of the Quiescent Intracellular Reservoir (QIR), or active, in the form of asymptomatic bacteriuria (ASB/ABU) or chronic cystitis. In mice, the fate of bladder infection: QIR, ASB, or chronic cystitis, is determined within the first 24 hours of infection and constitutes a putative host-pathogen mucosal checkpoint that contributes to susceptibility to recurrent cystitis. Knowledge of these checkpoints and bottlenecks is critical for our understanding of bladder infection and efforts to devise novel therapeutic strategies. PMID:22404313

  7. 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.

  8. 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...... to Cdc20, the mitotic co-activator of the APC/C, thereby inhibiting progression into anaphase. Mad2 exists in at least two different conformations, open-Mad2 (O-Mad2) and closed-Mad2 (C-Mad2), with the latter representing the active form that is able to bind Cdc20. Our ability to dissect Mad2 biology...... in vivo is limited by the absence of monoclonal antibodies (mAbs) useful for recognizing the different conformations of Mad2. Here, we describe and extensively characterize mAbs specific for either O-Mad2 or C-Mad2, as well as a pan-Mad2 antibody, and use these to investigate the different Mad2 complexes...

  9. 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

    The spindle assembly checkpoint (SAC) ensures accurate chromosome segregation by delaying entry into anaphase until all sister chromatids have become bi-oriented. A key component of the SAC is the Mad2 protein, which can adopt either an inactive open (O-Mad2) or active closed (C-Mad2) conformation....... 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...... 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...

  10. 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.

  11. Oncogenic pathways that affect antitumor immune response and immune checkpoint blockade therapy.

    Science.gov (United States)

    Zhao, Xianda; Subramanian, Subbaya

    2018-01-01

    Mechanistic insights of cancer immunology have led to the development of immune checkpoint blockade therapy (ICBT), which has elicited a remarkable clinical response in some cancer patients. Increasing evidence suggests that activation of oncogenic pathways, such as RAS/RAF/MAPK and PI3K signaling, impairs the antitumor immune response. Such oncogenic signaling, in turn, activates many inhibitory factors, including expression of immune checkpoint genes-allowing active infiltration of immunosuppressive cells into the tumor environment and inducing resistance against T-cell killing. In preclinical tumor models, effective targeting of oncogenic pathways has enhanced the response to ICBT. Ongoing clinical trials are now evaluating combination therapy (i.e., the use of oncogenic pathway inhibitors in combination with ICBT). However, more translational and clinical research is needed, to optimize ICBT doses and sequence, minimize toxicity, and assess the impact on study participants of certain genetic backgrounds. Also, it is crucial to understand whether wild-type tumors with elevated oncogenic signaling will respond to combination therapy. Insights gained through current and future translational studies will provide the scientific premise and rationale to target 1 or more oncogenic pathways in ICBT-resistant tumors, thus enabling more human patients to benefit from combination therapy. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. 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

  13. Tumor Immunology and Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer.

    Science.gov (United States)

    Jung, Chi Young; Antonia, Scott J

    2018-01-01

    Lung cancer is one of the most commonly diagnosed cancers and the leading cause of cancer-related deaths worldwide. Although progress in the treatment of advanced non-small cell lung cancer (NSCLC) has been made over the past decade, the 5-year survival rate in patients with lung cancer remains only 10%-20%. Obviously, new therapeutic options are required for patients with advanced NSCLC and unmet medical needs. Cancer immunotherapy is an evolving treatment modality that uses a patient's own immune systems to fight cancer. Theoretically, cancer immunotherapy can result in long-term cancer remission and may not cause the same side effects as chemotherapy and radiation. Immuno-oncology has become an important focus of basic research as well as clinical trials for the treatment of NSCLC. Immune checkpoint inhibitors are the most promising approach for cancer immunotherapy and they have become the standard of care for patients with advanced NSCLC. This review summarizes basic tumor immunology and the relevant clinical data on immunotherapeutic approaches, especially immune checkpoint inhibitors in NSCLC. Copyright©2018. The Korean Academy of Tuberculosis and Respiratory Diseases.

  14. 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.

  15. 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

  16. Successful treatment of arthritis induced by checkpoint inhibitors with tocilizumab: a case series.

    Science.gov (United States)

    Kim, Sang Taek; Tayar, Jean; Trinh, Van Anh; Suarez-Almazor, Maria; Garcia, Salvador; Hwu, Patrick; Johnson, Daniel Hartman; Uemura, Marc; Diab, Adi

    2017-12-01

    Immune checkpoint inhibitors (ICIs) have significantly improved outcomes for patients with numerous cancers. However, these therapies are associated with immune-related adverse events (irAEs), which are inflammatory side effects potentially affecting any organ. Cases of ICI-induced inflammatory arthritis have also been reported. In general, mild irAEs are treated with corticosteroids, while tumour necrosis factor-α (TNFα) inhibitors are reserved for refractory cases. However, prolonged use of TNFα inhibitor (TNFαi) can induce widespread, significant immunosuppression, which can negatively impact the antitumour efficacy of ICI therapy. Therefore, in clinical scenarios where patients develop severe immunotherapy-induced irAEs, an unmet need exists for alternative therapeutic strategies that are effective and without immune dampening effects. The anti-interleukin (IL)-6 receptor antibody, tocilizumab, is a biological agent Food and Drug Administration approved for the treatment of rheumatoid arthritis and juvenile idiopathic arthritis. Here, we report on three patients who developed severe polyarthritis while receiving ICI therapy and were treated with tocilizumab. All three patients demonstrated significant clinical improvement; one patient maintained a durable antitumour response derived from checkpoint inhibition. These three cases suggest that anti-IL-6 receptor antibody may be an effective alternative to corticosteroids or TNFαi for the treatment of arthritis irAEs. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  17. French immigration policy since May 1981.

    Science.gov (United States)

    Deley, M

    1983-01-01

    Examining the immigration policy changes undertaken by Socialist President Francois Mitterand between May 1981 and September 1982, this discussion provides backgroung information for the study of immigration policy reform in France, discusses the institutional and historical contexts within which recent policy changes have occurred, and examines the initial measures taken, the new immigration legislation adopted in October 1981, the "Exceptional Regularization" carried out in 1981-82, and various other immigration measures announced during the period under study. The discussion also identifies some of the problems which arose and are likely to arise as a result of the new policies. The French government has historically taken great pains to track the movement of both foreigners and natives within its territory. All citizens are issued a national identity card, and all foreigners residing in the country for longer than 3 months must obtain a residence permit from their local prefecture of police. The entry of some 347 million people annually into France must contribute to the problem of exercising strict control at entry. French measures to enforce immigration laws within its borders have not prevented the development of clandestine immigration nor the employment of undocumented foreigners. French law requires that all employers and employees contribute to the system of the Securite Sociale and to a variety of other government programs providing social and economic assistance to workers and their families. The year 1932 marks the date of the first French laws limiting immigration. On July 5, 1974 the French government closed the country's borders to immigration and have not reopened them since. Following that date a more severe attitude towards clandestine immigration became evident. Despite the anti-immigration policies of the 1974-81 period the number of foreigners residing in France did not diminish. 3 basic goals guided the new government in the development of

  18. 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.

  19. 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...

  20. [Patterns and specific features of immigration in Portugal].

    Science.gov (United States)

    Machado, F L

    1997-06-01

    "With...present international migration trends as its scenario, this article analyses the growth of immigration in Portugal, emphasising four main aspects: the balance between immigration and the recent resumption of emigration; the factors which have favoured the entry of immigrants; the composition of these immigrants in terms of country of origin; and the specific characteristics of Portuguese immigration in the context of the European Union." (EXCERPT)

  1. Local Immigration Enforcement and Arrests of the Hispanic Population

    OpenAIRE

    Michael Coon

    2017-01-01

    Section 287(g) of the Immigration and Nationality Act (INA), which was added to the INA by the Illegal Immigration Reform and Immigrant Responsibility Act of 1996 (IIRIRA), allows the federal government to enter into voluntary partnerships with state and local law enforcement agencies to enforce immigration law. Upon entering these agreements, law enforcement officers are trained by Immigration and Customs Enforcement (ICE) and receive delegated authority to enquire about an individual’s immi...

  2. Social anthropological study of immigration/immigrants through the eyes of local immigrant artists -exploring empowerment of immigrants and their identity construction through music in highly developed and multicultural society of Oslo, Norway

    OpenAIRE

    Nakata, Daisuke

    2014-01-01

    With the ever-increasing inflow of immigrants, issues surrounding immigration and immigrants in Oslo/Norway continue to be a hot topic in Norwegian news media and public debate today. In the academia, immigration-related topics have been likewise an interest of many social science researchers. As an attempt to address familiar topics in the field of immigration studies from a fresh and different perspective, this paper is a social anthropological study which focuses on immigran...

  3. IMMIGRATION AND INTEGRATION POLICIES IN UK

    Directory of Open Access Journals (Sweden)

    Anca Voicu

    2009-06-01

    Full Text Available The number of immigrants received by the United Kingdom significantly increased during the past several years. Given the set of economic and social difficulties encountered, UK created for the first time a completely original system of Nationality Legislation and started to apply a severe policy of assimilation instead of integration. UK applied the Community Law concerning immigration, asylum and free movement of workers in its national interest, the whole European construction showing the “British specificities”. Even today, there are a lot of measures to be taken in order to come to a real integration policy of immigrants.

  4. 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

  5. Welfare work addressing immigrants and refugees

    DEFF Research Database (Denmark)

    Øland, Trine

    In this presentation I will discuss the ways in which welfare workers addressing immigrants and refugees (re)produce integrationist visions, symbolizing society as an integrated whole and immigrants/refugees as a distraction to that whole. Paradoxically, welfare workers also oppose...... these integrationist visions in their quest to protect immigrants’ and refugees’ fundamental wellbeing and status as human beings with equal rights, group life and history. These opposing elements generate ambiguity and contradiction within integrationist welfare work. The ambition of the presentation is to enquire......, nurses and more) addressing immigrants and refugees and their families and descendants in the Danish welfare nation-state....

  6. ADVANCES OF THE COMPREHENSIVE IMMIGRATION REFORM AGENDA IN AN AMERICAN SANCTUARY CITY FOR IMMIGRANTS

    Directory of Open Access Journals (Sweden)

    Paola Virginia Suárez Ávila

    2014-01-01

    Full Text Available The analysis of immigration policy on a local space is an important contribution by emphasis on the need for local governments in the United States to redefine its role in the state, which involves thinking about re-emerging activism of local governments thta has promoted the generation of new practices and immigration laws in local governments in the United States in the context of Immigration Reform debate.

  7. Immigration Status, Visa Types, and Body Weight Among New Immigrants in the United States.

    Science.gov (United States)

    Yeh, Ming-Chin; Parikh, Nina S; Megliola, Alison E; Kelvin, Elizabeth A

    2018-03-01

    To investigate the relationship between immigration-related factors and body mass index (BMI) among immigrants. Secondary analyses of cross-sectional survey data. The New Immigrant Survey (NIS-2003) contains data from in-person or telephone interviews between May and November 2003, with a probability sample of immigrants granted legal permanent residency in the United States. A total of 8573 US immigrants. The NIS-2003 provided data on sociobehavioral domains, including migration history, education, employment, marital history, language, and health-related behaviors. The visa classifications are as follows: (1) family reunification, (2) employment, (3) diversity, (4) refugee, and (5) legalization. Nested multivariable linear regression analysis was used to estimate the independent relationships between BMI and the variables of interest. Overall, 32.6% of participants were overweight and 11.3% were obese (mean BMI = 25). Participants who were admitted to the United States with employment, refugee, or legalization visas compared with those who came with family reunion visas had a significantly higher BMI ( P < .001, P < .001, P < .01, respectively). Duration in the United States predicted BMI, with those immigrants in the United States longer having a higher BMI ( P < .001). Our findings suggest that immigrants who obtain particular visa categorizations and immigration status might have a higher risk of being overweight or obese. Immigrants need to be targeted along with the rest of the US population for weight management interventions.

  8. Immigration, naturalization and the Constitution.

    Science.gov (United States)

    Vecoli, R J

    1987-03-01

    This essay focuses upon major decisions made by the US government affecting aliens and the constitutional bases for them. These include: 1) the admission and exclusion of aliens, 2) the deportation of aliens, 3) the rights of aliens within the US, and 4) naturalization and denaturalization. The recourse to the extra-constitutional doctrine of sovereignty by the Supreme Court was the source of the plenary power of the Congress over immigration, thus denying the authority of the judiciary to extend the guarantees of due process of law and the equal protection of the law to aliens. The courts in the last 2 decades have assumed a more activist posture with respect to the rights of aliens, extending a greater degree of constitutional protection to the security of acquired citizenship and to the rights of due process and equal protection of foreigners, even to undocumented aliens.

  9. Immigration, social cohesion, and naturalization

    DEFF Research Database (Denmark)

    Lægaard, Sune

    2010-01-01

    social trust do not connect with issues of naturalization at all. Other conceptions of social cohesion are either politically controversial, problematic as part of the justification of stricter naturalization requirements, or in fact justify less demanding naturalization requirements.......The standard appeal to social cohesion in relation to immigration concerns admittance and residence. But social cohesion is sometimes also invoked as a relevant concern in relation to the attainment of citizenship in the state through naturalization. Many western states have recently tightened...... conditions for naturalization and introduced tougher language requirements and knowledge of society tests. The article discusses how concerns for social cohesion might function as a part of justifications of such restrictive naturalization requirements. It argues that standard concerns with generalized...

  10. 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...

  11. 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

  12. Expression and function analysis of mitotic checkpoint genes identifies TTK as a potential therapeutic target for human hepatocellular carcinoma.

    Directory of Open Access Journals (Sweden)

    Xiao-Dong Liang

    Full Text Available The mitotic spindle checkpoint (SAC genes have been considered targets of anticancer therapies. Here, we sought to identify the attractive mitotic spindle checkpoint genes appropriate for human hepatocellular carcinoma (HCC therapies. Through expression profile analysis of 137 selected mitotic spindle checkpoint genes in the publicly available microarray datasets, we showed that 13 genes were dramatically up-regulated in HCC tissues compared to normal livers and adjacent non-tumor tissues. A role of the 13 genes in proliferation was evaluated by knocking them down via small interfering RNA (siRNA in HCC cells. As a result, several mitotic spindle checkpoint genes were required for maintaining the proliferation of HCC cells, demonstrated by cell viability assay and soft agar colony formation assay. Then we established sorafenib-resistant sublines of HCC cell lines Huh7 and HepG2. Intriguingly, increased TTK expression was significantly associated with acquired sorafenib-resistance in Huh7, HepG2 cells. More importantly, TTK was observably up-regulated in 46 (86.8% of 53 HCC specimens. A series of in vitro and in vivo functional experiment assays showed that TTK overexpression promoted cell proliferation, anchor-dependent colony formation and resistance to sorafenib of HCC cells; TTK knockdown restrained cell growth, soft agar colony formation and resistance to sorafenib of HCC cells. Collectively, TTK plays an important role in proliferation and sorafenib resistance and could act as a potential therapeutic target for human hepatocellular carcinoma.

  13. 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

  14. 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

  15. Health disparities between immigrant and Danish cleaners

    DEFF Research Database (Denmark)

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

    2011-01-01

    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...... 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...... 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...

  16. Children and young people in immigration detention.

    Science.gov (United States)

    Dudley, Michael; Steel, Zachary; Mares, Sarah; Newman, Louise

    2012-07-01

    This article reviews evidence about the impact of immigration detention and other restrictive immigration policies on the mental health of children, young people and the adults who care for them. We review the implications of this for clinicians attempting to assess or work with incarcerated child and adult refugees and asylum seekers. There are increasing numbers of adults and children seeking asylum across the globe and many nations use incarceration and other harsh and interceptive immigration practices. There is mounting evidence of the psychological harm associated with detention of already vulnerable adults and children. Australia is used as a case study. Clinicians are required to consider the intersection of mental health assessment and treatment with human rights violations, and the impact of restrictive immigration policies, not only on asylum seekers and refugees but also on clinicians, clinical practice and professional ethics.

  17. Immigration and health care reform: shared struggles.

    Science.gov (United States)

    Gardner, Deborah B

    2007-01-01

    The connection between health care and immigration share overlaping key areas in policy reform. General concern, anger, and fear about immigration has been spreading nationwide. While illegal immigrants' use of expensive emergency department services does add to the cost for uncompensated care, this expenditure is not a primary cost driver but more a symptom of little or no access to preventative or primary health care. As a result of federal inaction, more state politicians are redefining how America copes with illegal residents including how or whether they have access to health care. The overlap of immigration and health care reform offers an opportunity for us to enter the next round of debate from a more informed vantage point.

  18. [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.

  19. 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...

  20. The Acceleration of Immigrant Unhealthy Assimilation.

    Science.gov (United States)

    Giuntella, Osea; Stella, Luca

    2017-04-01

    It is well known that immigrants tend to be healthier than US natives and that this advantage erodes with time spent in the USA. However, we know less about the heterogeneity of these trajectories among arrival cohorts. Recent studies have shown that later arrival cohorts of immigrants have lower entry wages and experience less economic assimilation. In this paper, we investigate whether similar cohort effects can be observed in the weight assimilation of immigrants in the USA. Focusing on obesity, we show that more recent immigrant cohorts arrive with higher obesity rates and experience a faster 'unhealthy assimilation' in terms of weight gain. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  1. News media consumption among immigrants in Europe

    DEFF Research Database (Denmark)

    Christiansen, Connie Carøe

    2004-01-01

    In recent years, especially with the advent of Digital Broadcasting Technology, transnational media has become central in the consumption of news by immigrant populations. This has received some attention as a factor associated with lack of integration into their new societies. The present article...... international news than is currently the national television channels, are also part of the picture. A diaspora perspective transforms the prospect presented by observers and journalists, worried about integration processes, and prompts considerations that immigrants are also emigrants....

  2. Mental illness disclosure in Chinese immigrant communities

    OpenAIRE

    Chen, Fang-pei; Ying-Chi Lai, Grace; Yang, Lawrence

    2013-01-01

    Support from social networks is imperative to mental health recovery of persons with mental illness. However, disclosing mental illness may damage a person’s participation in networks due to mental illness stigma, especially in Chinese-immigrant communities where social networks (the guanxi network) has specific social-cultural significance. This study focused on mental illness disclosure in Chinese-immigrant communities in New York City. Fifty-three Chinese psychiatric patients were recruite...

  3. 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...

  4. Wage Assimilation of Immigrants in Spain

    OpenAIRE

    Zenón Jiménez-Ridruejo; Carlos Borondo Arribas

    2011-01-01

    In this study we quantify the effect of the years of residence in Spain on the earnings of immigrants. We take sex, origin, education and age into account. The results are clearly positive, the longer the length of residence the more earnings, confirming the hypothesis of wage assimilation of immigrants as their human capital is adapted to the Spanish labor market. The information used comes from the Social Security’s Continuous Sample of Working Lives 2007. Additionally, we merge the earning...

  5. 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...

  6. 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.

  7. State Dependence in Unemployment among Danish Immigrants

    DEFF Research Database (Denmark)

    Ahmad, Nisar

    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....

  8. 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.

  9. Immigration Policy and Macroeconomic Performances in France

    OpenAIRE

    d'Albis, Hippolyte; Boubtane, Ekrame; Coulibaly, Dramane

    2013-01-01

    This paper proposes a quantitative assessment of the interaction between the Gross Domestic Product (GDP) per capita and the unemployment rate, and permanent immigration in France over the period 1994-2008. It uses a new database where immigration is measured by the flow of issuing residence permits of more than one year to foreigners. The flow is distinguished by age, sex and nationality of the migrant and depends on the reason for issuing the permit. Estimation of vector autoregression mode...

  10. The Incidence of Major Cardiovascular Events in Immigrants to Ontario, Canada: The CANHEART Immigrant Study.

    Science.gov (United States)

    Tu, Jack V; Chu, Anna; Rezai, Mohammad R; Guo, Helen; Maclagan, Laura C; Austin, Peter C; Booth, Gillian L; Manuel, Douglas G; Chiu, Maria; Ko, Dennis T; Lee, Douglas S; Shah, Baiju R; Donovan, Linda R; Sohail, Qazi Zain; Alter, David A

    2015-08-31

    -Immigrants from ethnic minority groups represent an increasing proportion of the population in many high-income countries but little is known about the causes and amount of variation between various immigrant groups in the incidence of major cardiovascular events. -We conducted the Cardiovascular Health in Ambulatory Care Research Team (CANHEART) Immigrant study, a big data initiative, linking information from Citizenship and Immigration Canada's Permanent Resident database to nine population-based health databases. A cohort of 824 662 first-generation immigrants aged 30 to 74 as of January 2002 from eight major ethnic groups and 201 countries of birth who immigrated to Ontario, Canada between 1985 and 2000 were compared to a reference group of 5.2 million long-term residents. The overall 10-year age-standardized incidence of major cardiovascular events was 30% lower among immigrants compared with long-term residents. East Asian immigrants (predominantly ethnic Chinese) had the lowest incidence overall (2.4 in males, 1.1 in females per 1000 person-years) but this increased with greater duration of stay in Canada. South Asian immigrants, including those born in Guyana had the highest event rates (8.9 in males, 3.6 in females per 1000 person-years), along with immigrants born in Iraq and Afghanistan. Adjustment for traditional risk factors reduced but did not eliminate differences in cardiovascular risk between various ethnic groups and long-term residents. -Striking differences in the incidence of cardiovascular events exist among immigrants to Canada from different ethnic backgrounds. Traditional risk factors explain part but not all of these differences.

  11. 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.

  12. Understanding employment barriers among older Korean immigrants.

    Science.gov (United States)

    Rhee, Min-Kyoung; Chi, Iris; Yi, Jaehee

    2015-06-01

    This study involved an in-depth exploration of the employment barriers of older Korean immigrants in Los Angeles. This qualitative study used data obtained from 6 focus groups and 5 individual interviews. Participants were 36 older Korean immigrants living in Los Angeles, aged 50 years and older, and either unemployed or employed in part-time or full-time work. A grounded theory analytical approach and constant comparison method were used. Ten major themes emerged as employment barriers for older Korean immigrants and were categorized as stereotype, human capital, and acculturation barriers. Ageism among employers specific to Korean culture, lack of English proficiency, separation from U.S. culture, marginalization from both Korean and U.S. cultures, and lack of social networks were important themes. In addition, older Korean immigrants experienced multiple interconnected barriers. The findings highlight the importance of using a multidimensional approach to explore employment barriers among older Korean immigrants who face multiple obstacles in finding jobs. Implications for local governments and Korean communities and potential services to support employment opportunities for older Korean immigrants are discussed. © The Author 2013. 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.

  13. Immune Checkpoint Inhibitors for Treatment of Metastatic Melanoma of the Orbit and Ocular Adnexa.

    Science.gov (United States)

    Ford, Joshua; Thuro, Bradley A; Thakar, Sudip; Hwu, Wen-Jen; Richani, Karina; Esmaeli, Bita

    Programmed cell death 1 (PD-1) inhibitors are members of a new class of drugs known as immune checkpoint inhibitors and have proven efficacy in the treatment of metastatic melanoma. Herein, the authors report the use of nivolumab and pembrolizumab, 2 recently Food and Drug Administration-approved PD-1 inhibitors, in 3 patients: 1 with metastatic conjunctival melanoma and 2 with metastatic cutaneous melanoma and orbital involvement. The patients' metastatic disease responded well to drug treatment. As of this writing, 2 patients have completed therapy and remain disease free at least 1 year after treatment completion; the other patient is still receiving treatment, and his orbital disease is responding. The authors herein describe the use of PD-1 inhibitors as a new alternative in the treatment of metastatic melanoma to the orbit or metastatic ocular adnexal melanomas in these clinical settings.

  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...... substrates have hitherto been identified. RESULTS: Here, we combine a chemical genetics approach with high-resolution mass spectrometry to identify novel Chk1 substrates and their phosphorylation sites. The list of targets produced reveals the potential impact of Chk1 function not only on processes where Chk...... identification of KAP1 Ser473 phosphorylation as a robust readout for Chk1 activity could be used to explore the in vivo effects of Chk1 inhibitors that are being developed for clinical evaluation....

  15. 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

  16. 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.

  17. 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.

  18. 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......, whereas a second barrier is mediated by oncogene-induced senescence. The relationship between these two barriers, if any, has not been elucidated. Here we show that oncogene-induced senescence is associated with signs of DNA replication stress, including prematurely terminated DNA replication forks...... 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....

  19. Overcoming Barriers in Oncolytic Virotherapy with HDAC Inhibitors and Immune Checkpoint Blockade

    Science.gov (United States)

    Marchini, Antonio; Scott, Eleanor M.; Rommelaere, Jean

    2016-01-01

    Oncolytic viruses (OVs) target and destroy cancer cells while sparing their normal counterparts. These viruses have been evaluated in numerous studies at both pre-clinical and clinical levels and the recent Food and Drug Administration (FDA) approval of an oncolytic herpesvirus-based treatment raises optimism that OVs will become a therapeutic option for cancer patients. However, to improve clinical outcome, there is a need to increase OV efficacy. In addition to killing cancer cells directly through lysis, OVs can stimulate the induction of anti-tumour immune responses. The host immune system thus represents a “double-edged sword” for oncolytic virotherapy: on the one hand, a robust anti-viral response will limit OV replication and spread; on the other hand, the immune-mediated component of OV therapy may be its most important anti-cancer mechanism. Although the relative contribution of direct viral oncolysis and indirect, immune-mediated oncosuppression to overall OV efficacy is unclear, it is likely that an initial period of vigorous OV multiplication and lytic activity will most optimally set the stage for subsequent adaptive anti-tumour immunity. In this review, we consider the use of histone deacetylase (HDAC) inhibitors as a means of boosting virus replication and lessening the negative impact of innate immunity on the direct oncolytic effect. We also discuss an alternative approach, aimed at potentiating OV-elicited anti-tumour immunity through the blockade of immune checkpoints. We conclude by proposing a two-phase combinatorial strategy in which initial OV replication and spread is maximised through transient HDAC inhibition, with anti-tumour immune responses subsequently enhanced by immune checkpoint blockade. PMID:26751469

  20. Advances in T-cell checkpoint immunotherapy for head and neck squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Qi X

    2017-12-01

    Full Text Available Xinmeng Qi,1,2,* Bo Jia,3,* Xue Zhao,1 Dan Yu1 1Department of Otolaryngology Head and Neck Surgery, The Second Hospital, Jilin University, Changchun, Jilin, 2Department of Otolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, 3Department of Thoracic Medical Oncology, Peking University Cancer Hospital and Institute, Beijing People’s Republic of China *These authors contributed equally to this work Abstract: Head and neck squamous cell carcinoma (HNSCC has been found to be a complex group of malignancies characterized by their profound immunosuppression and high aggressiveness. In most cases of advanced HNSCC, treatment fails to obtain total cancer cure. Efforts are needed to develop new therapeutic approaches to improve HNSCC outcomes. In this light, T-cells “immune checkpoint” has attracted much attention in cancer immunotherapy. It has been broadly accepted that inhibitory T-cell immune checkpoints contribute to tumor immune escape through negative immune regulatory signals (cytotoxic T-lymphocyte-associated antigen 4 [CTLA-4], programmed cell death 1 [PD-1], B7-H3, and B7-H4, etc. Current data suggest that PD-1 and CTLA-4 receptors can inhibit T-cell receptors and T-cell proliferation. Blockade of PD-1/PD-L1 and/or CTLA-4/CD28 pathways has shown promising tumor outcomes in clinical trials for advanced solid tumors like melanoma, renal cell cancer, and non-small cell lung cancer. The present review attempts to explore what is known about PD-1/PD-L1 and CTLA-4/CD28 pathways with a focus on HNSCC. We further discuss how these pathways can be manipulated with therapeutic intent. Keywords: immune checkpoint, PD-1/PD-L1, CTLA-4, HNSCC, immunotherapy

  1. 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.

  2. Immune checkpoint inhibitors enhance cytotoxicity of cytokine-induced killer cells against human myeloid leukaemic blasts.

    Science.gov (United States)

    Poh, Su Li; Linn, Yeh Ching

    2016-05-01

    We studied whether blockade of inhibitory receptors on cytokine-induced killer (CIK) cells by immune checkpoint inhibitors could increase its anti-tumour potency against haematological malignancies. CIK cultures were generated from seven normal donors and nine patients with acute myeloid leukaemia (AML), acute lymphoblastic leukaemia (ALL) or multiple myeloma (MM). The inhibitory receptors B and T lymphocyte attenuator, CD200 receptor, lymphocyte activation gene-3 (LAG-3) and T cell immunoglobulin and mucin-domain-containing-3 (TIM-3) were present at variable percentages in most CIK cultures, while cytotoxic T lymphocyte-associated protein 4 (CTLA-4), programmed death-1 (PD-1) and killer cell immunoglobulin-like receptors (KIR2DL1/2/3) were expressed at low level in most cultures. Without blockade, myeloid leukaemia cells were susceptible to autologous and allogeneic CIK-mediated cytotoxicity. Blockade of KIR, LAG-3, PD-1 and TIM-3 but not CTLA-4 resulted in remarkable increase in killing against these targets, even in those with poor baseline cytotoxicity. ALL and MM targets were resistant to CIK-mediated cytotoxicity, and blockade of receptors did not increase cytotoxicity to a meaningful extent. Combination of inhibitors against two receptors did not further increase cytotoxicity. Interestingly, potentiation of CIK killing by blocking antibodies was not predicted by expression of receptors on CIK and their respective ligands on the targets. Compared to un-activated T and NK cells, blockade potentiated the cytotoxicity of CIK cells to a greater degree and at a lower E:T ratio, but without significant increase in cytotoxicity against normal white cell. Our findings provide the basis for clinical trial combining autologous CIK cells with checkpoint inhibitors for patients with AML.

  3. Owning the issues of crime and immigration: the relation between immigration and crime news and anti-immigrant voting in 11 countries

    NARCIS (Netherlands)

    Burscher, B.; van Spanje, J.; de Vreese, C.H.

    2015-01-01

    It is still not well understood how the media affect anti-immigrant party voting. In this paper, we argue and demonstrate empirically that mere exposure to immigration- and crime-related news is positively related to the likelihood that a voter casts a vote for an anti-immigrant party. On the basis

  4. 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'

  5. 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

  6. Chl12 (Ctf18) Forms a Novel Replication Factor C-Related Complex and Functions Redundantly with Rad24 in the DNA Replication Checkpoint Pathway

    OpenAIRE

    Naiki, Takahiro; Kondo, Tae; Nakada, Daisuke; Matsumoto, Kunihiro; Sugimoto, Katsunori

    2001-01-01

    RAD24 has been identified as a gene essential for the DNA damage checkpoint in budding yeast. Rad24 is structurally related to subunits of the replication factor C (RFC) complex, and forms an RFC-related complex with Rfc2, Rfc3, Rfc4, and Rfc5. The rad24Δ mutation enhances the defect of rfc5-1 in the DNA replication block checkpoint, implicating RAD24 in this checkpoint. CHL12 (also called CTF18) encodes a protein that is structurally related to the Rad24 and RFC proteins. We show here that a...

  7. 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

  8. 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…

  9. U.S. Immigration Policy, Immigrants' Ages, and U.S. Population Size.

    Science.gov (United States)

    Arthur, W. Brian; Espenshade, Thomas J.

    If U.S. birthrates remain below the replacement level and are relatively constant, and if immigration is constant both in total numbers and age-sex composition, population size will eventually become stationary, according to this policy discussion paper. Moverover, varying the constant annual number of immigrants produces an equal proportionate…

  10. American Elementary School Children's Attitudes about Immigrants, Immigration, and Being an American

    Science.gov (United States)

    Brown, Christia Spears

    2011-01-01

    The current study examined 5 to 11-year-old European American children's (N = 90) attitudes regarding immigrants, immigration policy, and what it means to be an American. The majority of children in the sample (from a predominantly European American community) held strong American identities and had distinct ideas about what it means to be an…

  11. 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.

  12. Illegal Immigration and the Colonization of the American Labor Market. Center for Immigration Studies Paper 1.

    Science.gov (United States)

    Martin, Philip L.

    This paper finds that the ready availability of illegal-immigrant workers from Mexico in major industries in the Southwest region of the United States is having far-reaching and often unanticipated consequences for patterns of investment, employment, and business competition. It reviews the displacement of U.S. workers by illegal immigrants in…

  13. Illuminating Agency: A Latin@ Immigrant Parent's "Testimonio" on the Intersection of Immigration Reform and Schools

    Science.gov (United States)

    Fernández, Erica

    2016-01-01

    Anti-immigration reform has created a hostile and threatening climate for Latin@ immigrants and their families. Simple everyday acts that are often taken for granted (i.e. parents dropping off children at school, driving to the grocery store, etc.) became acts that threaten to separate families. As a result, many Latin@ families are currently…

  14. 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…

  15. 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.

  16. 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

  17. Adolescent Body Image Distortion: A Consideration of Immigrant Generational Status, Immigrant Concentration, Sex and Body Dissatisfaction.

    Science.gov (United States)

    Kimber, Melissa; Georgiades, Katholiki; Couturier, Jennifer; Jack, Susan M; Wahoush, Olive

    2015-11-01

    Immigrant adolescents represent a significant and growing proportion of the population in the United States. Yet, little is known about their experiences of body image distortion. This is particularly concerning given that body image distortion has been identified as a significant and modifiable risk factor for a number of mental illnesses, including depression and eating disorders. This study uses multi-level modeling to examine the associations between immigrant generational status, neighborhood immigrant concentration, sex, body dissatisfaction and risk for body image distortion. Data come from the National Longitudinal Study of Adolescent Health and includes 10,962 11-19 year olds (49.6 % female). First generation immigrant females were significantly more likely than 3rd generation-or-later adolescents to experience underweight body image distortion. There was no association between neighborhood immigrant concentration and risk for body image distortion. Body dissatisfaction was associated with greater risk for underweight and overweight body image distortion, with the magnitude of underweight distortion risk significantly greater among 1st generation immigrants. Interventions that encourage the development of a healthy body image have the potential to reduce the onset and duration of body image distortion among immigrant and non-immigrant adolescents.

  18. 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.

  19. Immigration Regimes and Schooling Regimes: Which Countries Promote Successful Immigrant Incorporation?

    Science.gov (United States)

    Hochschild, Jennifer L.; Cropper, Porsha

    2010-01-01

    While Canada is often described as the most and France as one of the least successful countries in the realm of immigrant incorporation, the question remains unresolved of how to evaluate a country's policies for dealing with immigration and incorporation relative to that of others. Our strategy is to examine the relationships among (1) countries'…

  20. A Comparative Assessment of Public Opinion toward Immigrants and Immigration Policies.

    Science.gov (United States)

    Simon, Rita J.; Lynch, James P.

    1999-01-01

    Studied public attitudes toward immigration in seven countries (Australia, Canada, France, Germany, Great Britain, Japan, and the United States) for 1970 through 1995 as part of a larger, ongoing study. Countries with major differences in statutes, policies, and practices related to immigration nevertheless share many attitudes and beliefs about…

  1. Connecting Worlds: Using Photo Narrations to Connect Immigrant Children, Preschool Teachers, and Immigrant Families

    Science.gov (United States)

    Strickland, Martha J.; Keat, Jane B.; Marinak, Barbara A.

    2010-01-01

    Increases in immigrant children to U.S. preschools have introduced unique challenges to teachers. An awareness of disconnections between a homogeneous teaching population and the increasingly diverse student population calls for additional exploration of enhancing connections to facilitate the young immigrants' learning process in the classroom.…

  2. The impact of illegal immigration on U.S. economy

    OpenAIRE

    Maha, Sorin-Stefan; Maha, Liviu-George

    2009-01-01

    This paper explores the impact of the illegal immigration on the U.S. economy in a context where the immigration phenomenon in this country is one of scale, taking into account its effects on the labor market, on consumption, budget equilibrium and American business. Nation founded by immigrants, the U.S. is facing the problem of immigrants, who are spread throughout the country. There are different opinions about the high number of immigrants on U.S. soil, immigration being considered benefi...

  3. 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

  4. Development of the Stress of Immigration Survey (SOIS): a Field Test among Mexican Immigrant Women

    Science.gov (United States)

    Sternberg, Rosa Maria; Nápoles, Anna Maria; Gregorich, Steven; Paul, Steven; Lee, Kathryn A.; Stewart, Anita L.

    2016-01-01

    The Stress of Immigration Survey (SOIS) is a screening tool used to assess immigration-related stress. The mixed methods approach included concept development, pretesting, field-testing, and psychometric evaluation in a sample of 131 low-income women of Mexican descent. The 21-item SOIS screens for stress related to language; immigrant status; work issues; yearning for family and home country; and cultural dissonance. Mean scores ranged from 3.6 to 4.4 (1-5 scale, higher is more stress). Cronbach's alphas >.80 for all sub-scales. The SOIS may be a useful screening tool for detecting high levels of immigration-related stress in low-income Mexican immigrant women. PMID:26605954

  5. Development of the Stress of Immigration Survey: A Field Test Among Mexican Immigrant Women.

    Science.gov (United States)

    Sternberg, Rosa Maria; Nápoles, Anna Maria; Gregorich, Steven; Paul, Steven; Lee, Kathryn A; Stewart, Anita L

    2016-01-01

    The Stress of Immigration Survey (SOIS) is a screening tool used to assess immigration-related stress. The mixed methods approach included concept development, pretesting, field testing, and psychometric evaluation in a sample of 131 low-income women of Mexican descent. The 21-item SOIS screens for stress related to language, immigrant status, work issues, yearning for family and home country, and cultural dissonance. Mean scores ranged from 3.6 to 4.4 (a scale of 1-5, higher is more stress). Cronbach α values were more than 0.80 for all subscales. The SOIS may be a useful screening tool for detecting high levels of immigration-related stress in low-income Mexican immigrant women.

  6. 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.

  7. 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...

  8. 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

  9. Time lag between immigration and tuberculosis rates in immigrants in the Netherlands: a time-series analysis.

    Science.gov (United States)

    van Aart, C; Boshuizen, H; Dekkers, A; Korthals Altes, H

    2017-05-01

    In low-incidence countries, most tuberculosis (TB) cases are foreign-born. We explored the temporal relationship between immigration and TB in first-generation immigrants between 1995 and 2012 to assess whether immigration can be a predictor for TB in immigrants from high-incidence countries. We obtained monthly data on immigrant TB cases and immigration for the three countries of origin most frequently represented among TB cases in the Netherlands: Morocco, Somalia and Turkey. The best-fit seasonal autoregressive integrated moving average (SARIMA) model to the immigration time-series was used to prewhiten the TB time series. The cross-correlation function (CCF) was then computed on the residual time series to detect time lags between immigration and TB rates. We identified a 17-month lag between Somali immigration and Somali immigrant TB cases, but no time lag for immigrants from Morocco and Turkey. The absence of a lag in the Moroccan and Turkish population may be attributed to the relatively low TB prevalence in the countries of origin and an increased likelihood of reactivation TB in an ageing immigrant population. Understanding the time lag between Somali immigration and TB disease would benefit from a closer epidemiological analysis of cohorts of Somali cases diagnosed within the first years after entry.

  10. Immigration in two federations: Canada and Australia.

    Science.gov (United States)

    Atchison, J

    1988-03-01

    The need for increasingly widespread application of a policy or program, settlement, and multiculturalism is urgent in both Canada and Australia. For both countries there is a clear pattern of coalescence and divergence and the distinct growth of immigration as a federal function. While Australia has strengthened federal functions in a area of increasingly geo-political need, Canada is moving towards a looser model of federalism. By 1918 both countries were strengthening their federal functions in immigration as discussions within the British Empire on the recommendations of the 1917 Dominions Royal Commission took root. Both countries were interested in agricultural immigration and land settlement. The Great Depression caused a major reduction in population growth rates. From 1933-1948 Canada had a poor record of providing sanctuary for Jews. In Australia, however, Jewish voluntary agencies were aiding the reception of refugees by 1937. The 1st permanent embodiment of commonwealth jurisdiction over immigration was the establishment of an Immigration Branch within the Department of Interior around 1938. Australia needed extra population for defense. The major structural link between government and the immigrant communities was through the Good Neighbor Movement, which began on a nationwide basis in 1950. Both Canada and Australia are major receiving countries for refugees. In 1973 Australia reached the position of effective, practical nondiscrimination achieved by Canada in 1967. Prime Minister Trudeau's policy was multiculturalism within a framework of bilingualism. By 1978 Australia had a new federalism policy, which in all areas concerned with immigrants, refugees and ethnicity, rationalized resources allocation and imposed a political philosophy. The foci of multiculturalism in Australia are 1) community languages; 2) creation of a tolerant, non-discriminatory society; and 3) equity and participation. In 1978 Australia specified population replacement and

  11. Immigration, integration and support for redistribution in Europe

    NARCIS (Netherlands)

    Burgoon, B.

    2014-01-01

    Immigration poses individual or collective economic risks that might increase citizen support for government redistribution, but it can also generate fiscal pressure or undermine social solidarity to diminish such support. These offsetting conditions obscure the net effects of immigration for

  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. Smoking characteristics of Polish immigrants in Dublin

    Directory of Open Access Journals (Sweden)

    Zatonski Witold

    2008-12-01

    Full Text Available Abstract Background This study examined two main hypotheses: a Polish immigrants' smoking estimates are greater than their Irish counterparts (b Polish immigrants purchasing cigarettes from Poland smoke "heavier" (≥ 20 cigarettes a day when compared to those purchasing cigarettes from Ireland. The study also set out to identify significant predictors of 'current' smoking (some days and everyday among the Polish immigrants. Methods Dublin residents of Polish origin (n = 1,545 completed a previously validated Polish questionnaire in response to an advertisement in a local Polish lifestyle magazine over 5 weekends (July–August, 2007. The Office of Tobacco Control telephone-based monthly survey data were analyzed for the Irish population in Dublin for the same period (n = 484. Results Age-sex adjusted smoking estimates were: 47.6% (95% Confidence Interval [CI]: 47.3%; 48.0% among the Poles and 27.8% (95% CI: 27.2%; 28.4% among the general Irish population (p 24 months were significant predictors of current smoking among the Poles. An objective validation of the self-reported smoking history of a randomly selected sub-sample immigrant group, using expired carbon monoxide (CO measurements, showed a highly significant correlation coefficient (r = 0.64 of expired CO levels with the reported number of cigarettes consumed (p Conclusion Polish immigrants' smoking estimates are higher than their Irish counterparts, and particularly if employed, with only primary-level education, and are overseas >2 years.

  16. Health care and the illegal immigrant.

    Science.gov (United States)

    Glen, Patrick

    2013-01-01

    The question of whether illegal immigrants should be entitled to some form of health coverage in the United States sits at the intersection of two contentious debates: health reform and immigration reform. Proponents of extending coverage argue that the United States has a moral obligation to provide health care to all those within its borders. Conversely, those against doing so argue that immigrants illegally present in the country should not be entitled to public benefits. This Article seeks to chart a middle course between these extremes while answering two questions. First, does constitutional law mandate extending health coverage to illegal immigrants? Second, even if not legally mandated, are there compelling policy reasons for extending such coverage? This Article concludes that while health coverage for illegal immigrants is not required under prevailing constitutional norms, extending coverage as a matter of policy would serve the broader interests of the United States. Extending coverage would be beneficial as a matter of economics and public health, generating spillover benefits for all US citizens and those in the US healthcare and health insurance systems.

  17. Association between Integration Policies and Immigrants' Mortality

    DEFF Research Database (Denmark)

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

    2015-01-01

    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...... between immigrants and the local-born population were also largest in Denmark and lowest in France (e.g., Turkish-born men MRR 1.52; 95% CI 1.38-1.67 and 0.62; 0.58-0.66, respectively). These patterns were consistent across all age groups, and more marked for cardiovascular diseases. CONCLUSIONS: Although......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...

  18. 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.

  19. U.S. Immigration Policy on Haitian Migrants

    Science.gov (United States)

    2010-03-31

    Committee on the Judiciary, Subcommittee on Immigration , Hearing on the Detention and Treatment of Haitian Asylum Seekers , October 1, 2002. (Hereafter... Asylum Seekers : Haitians in Comparative Context, by Ruth Ellen Wasem. (Archived report available upon request.) . U.S. Immigration Policy on Haitian...another form of immigration relief, it opted not to include Haitian asylum seekers . The following year, Congress enacted the Haitian Refugee Immigration

  20. Immigration Status and Victimization: Evidence from the British Crime Survey

    OpenAIRE

    Georgios Papadopoulos

    2013-01-01

    This study, using data from the British Crime Survey (BCS), examines the microrelationship between immigration and victimization. We first find that, although immigrants are more likely to suffer property crimes than natives, this is well explained by the fact that immigrants exhibit demographic characteristics associated with higher victimization. Contrary to the above, immigrants are of lower risk of violent victimization. As violence is an expressive type of crime, where interactions betwe...

  1. 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...

  2. 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...

  3. Clinical features, predictive correlates, and pathophysiology of immune-related adverse events in immune checkpoint inhibitor treatments in cancer: a short review

    OpenAIRE

    Yoest, Jennifer M

    2017-01-01

    Jennifer M Yoest Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA Abstract: Identification and characterization of T-cell regulatory mechanisms, or checkpoints, have led to a wave of drug development aimed at inhibiting these targets to “remove the brakes” of the immune system. This class of anticancer therapeutics, termed immune checkpoint inhibitors (ICIs), has harnessed the potential of the body’s own immune system to reco...

  4. 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

  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.

  6. 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

  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. Obstetric and perinatal outcomes among immigrant and non-immigrant women in Berlin, Germany.

    Science.gov (United States)

    David, Matthias; Borde, Theda; Brenne, Silke; Ramsauer, Babett; Henrich, Wolfgang; Breckenkamp, Jürgen; Razum, Oliver

    2017-10-01

    In Germany, regular immigrants and their descendants have legal and financial access to health care equal to the general citizenry. Nonetheless, some of their health outcomes are comparatively unfavorable, and that is only partially explained by their lower socioeconomic status (SES). The aim of this study was to assess whether this disparity exists also for obstetric and perinatal outcomes. We compared obstetric and perinatal outcomes between immigrant women (first or second generation) and non-immigrant women, delivering at three maternity hospitals in Berlin, Germany, 2011-2012. Multivariable logistic regression analysis was used to assess immigrant status and other possible risk factors for the baby being delivered preterm, small for gestational age (SGA), or transferred to neonatal care. The final database retained 6702 women, of whom 53.1% were first- or second-generation immigrants. First-generation Turkish immigrant women had significantly lower odds of preterm birth (OR 0.37, P outcomes. This study provides strong evidence that health disparities for obstetric and perinatal health outcomes do not exist in immigrants relative to native Germans, but exist instead in women without post-secondary-level education compared to women with such education, regardless of ethnicity or migration history.

  9. The Roles of microRNAs in Regulating the Expression of PD-1/PD-L1 Immune Checkpoint

    Science.gov (United States)

    Wang, Qingshui; Lin, Wei; Tang, Xiaoqiong; Li, Suhuan; Guo, Libin

    2017-01-01

    Engagement of programmed death-ligand 1 (PD-L1) with its receptor programmed death 1 (PD-1) on T cells has been speculated to play a major role in suppressing the immune system, which helps tumor cells evade anti-tumor immunity. With the development of whole genome sequencing technologies, microRNAs have gained more attention as an important new layer of molecular regulation. Recent studies have revealed that altered expression of microRNAs play a pivotal role in immune checkpoint and various cellular processes in cancer. In this review, we focused on the latest progress about microRNAs research which involves the regulation of PD-1/PD-L1 immune checkpoint. PMID:29186904

  10. The G2 checkpoint inhibitor CBP-93872 increases the sensitivity of colorectal and pancreatic cancer cells to chemotherapy.

    Directory of Open Access Journals (Sweden)

    Tsutomu Iwata

    Full Text Available CBP-93872 suppresses maintenance of DNA double-stranded break-induced G2 checkpoint, by inhibiting the pathway between ataxia-telangiectasia mutated (ATM and ATM- and Rad3-related (ATR activation. To examine the potential use of CBP-93872 for clinical applications, we analyzed the synergistic effects of platinum-containing drugs, oxaliplatin and cisplatin, pyrimidine antimetabolites, gemcitabine and 5-fluorouracil (5-FU, in combination with CBP-93872, on cell lethality in colorectal and pancreatic cancer cell lines. Treatment with CBP-93872 significantly increased cancer cell sensitivities to various chemotherapeutic agents tested through suppression of checkpoint activation. Our results thus reveal that combination treatment of CBP-93872 with known chemotherapeutic agents inhibits phosphorylation of ATR and Chk1, and induces cell death.

  11. The Roles of microRNAs in Regulating the Expression of PD-1/PD-L1 Immune Checkpoint

    Directory of Open Access Journals (Sweden)

    Qingshui Wang

    2017-11-01

    Full Text Available Engagement of programmed death-ligand 1 (PD-L1 with its receptor programmed death 1 (PD-1 on T cells has been speculated to play a major role in suppressing the immune system, which helps tumor cells evade anti-tumor immunity. With the development of whole genome sequencing technologies, microRNAs have gained more attention as an important new layer of molecular regulation. Recent studies have revealed that altered expression of microRNAs play a pivotal role in immune checkpoint and various cellular processes in cancer. In this review, we focused on the latest progress about microRNAs research which involves the regulation of PD-1/PD-L1 immune checkpoint.

  12. Premature Sister Chromatid Separation Is Poorly Detected by the Spindle Assembly Checkpoint as a Result of System-Level Feedback

    Directory of Open Access Journals (Sweden)

    Mihailo Mirkovic

    2015-10-01

    Full Text Available Sister chromatid cohesion, mediated by the cohesin complex, is essential for faithful mitosis. Nevertheless, evidence suggests that the surveillance mechanism that governs mitotic fidelity, the spindle assembly checkpoint (SAC, is not robust enough to halt cell division when cohesion loss occurs prematurely. The mechanism behind this poor response is not properly understood. Using developing Drosophila brains, we show that full sister chromatid separation elicits a weak checkpoint response resulting in abnormal mitotic exit after a short delay. Quantitative live-cell imaging approaches combined with mathematical modeling indicate that weak SAC activation upon cohesion loss is caused by weak signal generation. This is further attenuated by several feedback loops in the mitotic signaling network. We propose that multiple feedback loops involving cyclin-dependent kinase 1 (Cdk1 gradually impair error-correction efficiency and accelerate mitotic exit upon premature loss of cohesion. Our findings explain how cohesion defects may escape SAC surveillance.

  13. 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....

  14. 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...

  15. 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...

  16. 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...

  17. 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...

  18. 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...

  19. 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...

  20. 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…