WorldWideScience

Sample records for causeway immigration checkpoint

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1996-12-31

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

  2. Modeling the effect of Causeways on Circulation in the Banana River

    Science.gov (United States)

    Saberi, A.; Weaver, R. J.

    2015-12-01

    The Indian River Lagoon (IRL) is a restricted estuary along the east coast of Florida. Although Banana River, a 50 km long sub-basin of IRL, has an outlet to the ocean through the Port Canaveral locks, the locks remain closed when there is no passing vessel. The lack of direct ocean connection results in limited circulation, long flushing time and poor water quality. Existence of the causeways limits the circulation even more. In this study, the impact of the causeways on flushing time is studied. This study also examines the extent to which constructing a low crested weir adjacent to Port Canaveral can improve flushing in this region. ADCIRC 2DDI is forced with meteorological inputs as well as tides to simulate the hydrodynamic properties of the study area and determine the 2D depth-averaged velocity field for four separate cases: Existing System with and without consideration of the causeways, and modified system (adding a weir near port Canaveral) with and without consideration of the causeways. Passive particles are placed in Banana River, and their movement is tracked using a Lagrangian Particle Tracking Model (LPTM). Transport timescales are then computed, and residence time contours as well as pathlines of selected particles are plotted. Results indicate that the narrow raised pathway section of the causeways acts as a plate which diverts the flow direction and generates eddies in the downstream which causes the particles in the vicinity of the causeways remain in the domain for a longer duration. There is a longer residence time for the case in which the causeways are considered. The results with the added weir suggest a noticeable improvement in flushing time and residence time even for the case in which the causeways are considered in the model.

  3. Port Isabel (GIWW) Channel Improvements at the Queen Isabella Causeway. Laguna Madre, Texas, Navigation Improvement Project

    Science.gov (United States)

    2009-09-01

    ER D C/ CH L TR -0 9 -1 3 Port Isabel (GIWW) Channel Improvements at the Queen Isabella Causeway Laguna Madre , Texas, Navigation...Causeway Laguna Madre , Texas, Navigation Improvement Project Timothy W. Shelton, P.E. and Dennis Webb, P.E. Coastal and Hydraulics Laboratory U.S...distribution is unlimited. Prepared for U.S. Army Corps of Engineer District, Galveston Galveston, TX 77550 ERDC/CHL TR-09-13 ii Abstract: Laguna Madre is

  4. Proximate environmental drivers of coral communities at Palmyra Atoll: establishing baselines prior to removing a WWII military causeway.

    Science.gov (United States)

    Williams, Gareth J; Knapp, Ingrid S; Maragos, James E; Davy, Simon K

    2011-08-01

    A management proposal aims to partly remove a WWII military causeway at Palmyra Atoll to improve lagoon water circulation and alleviate sedimentation stress on the southeast backreef, an area of high coral cover and diversity. This action could result in a shift in sedimentation across reef sites. To provide management advice, we quantified the proximate environmental factors driving scleractinian coral cover and community patterns at Palmyra. The proportion of fine sedimentation was the optimal predictor of coral cover and changes in community structure, explaining 23.7% and 24.7% of the variation between sites, respectively. Scleractinian coral cover was negatively correlated with increases in fine sedimentation. Removing the causeway could negatively affect the Montipora corals that dominate the western reef terrace, as this genus was negatively correlated with levels of fine sedimentation. The tolerance limits of corals, and sediment re-distribution patterns, should be determined prior to complete removal of the causeway.

  5. Cambridge checkpoint English workbook 2

    CERN Document Server

    Reynolds, John

    2014-01-01

    Build confidence and understanding throughout the year with hundreds of additional practice questions. This Workbook supports our bestselling Checkpoint series, with exercises specifically matched to the Cambridge Progression tests and the Checkpoint tests. - Develops understanding and builds confidence ahead of assessment with exercises matched to the tests - Ensures a thorough understanding of all aspects of the course by following the structure of the relevant textbook - Saves planning time with exercises that are suitable for use in class or as homework This Workbook is

  6. Cambridge checkpoint English workbook 3

    CERN Document Server

    Reynolds, John

    2014-01-01

    Build confidence and understanding throughout the year with hundreds of additional practice questions. This Workbook supports our bestselling Checkpoint series, with exercises specifically matched to the Cambridge Progression tests and the Checkpoint tests. - Develops understanding and builds confidence ahead of assessment with exercises matched to the tests - Ensures a thorough understanding of all aspects of the course by following the structure of the relevant textbook - Saves planning time with exercises that are suitable for use in class or as homework This Workbook is

  7. Targeting checkpoint kinase 1 in cancer therapeutics.

    Science.gov (United States)

    Tse, Archie N; Carvajal, Richard; Schwartz, Gary K

    2007-04-01

    Progression through the cell cycle is monitored by surveillance mechanisms known as cell cycle checkpoints. Our knowledge of the biochemical nature of checkpoint regulation during an unperturbed cell cycle and following DNA damage has expanded tremendously over the past decade. We now know that dysfunction in cell cycle checkpoints leads to genomic instability and contributes to tumor progression, and most agents used for cancer therapy, such as cytotoxic chemotherapy and ionizing radiation, also activate cell cycle checkpoints. Understanding how checkpoints are regulated is therefore important from the points of view of both tumorigenesis and cancer treatment. In this review, we present an overview of the molecular hierarchy of the checkpoint signaling network and the emerging role of checkpoint targets, especially checkpoint kinase 1, in cancer therapy. Further, we discuss the results of recent clinical trials involving the nonspecific checkpoint kinase 1 inhibitor, UCN-01, and the challenges we face with this new therapeutic approach.

  8. 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.

  9. Checkpoint Blockade in Cancer Immunotherapy

    Science.gov (United States)

    Korman, Alan J.; Peggs, Karl S.; Allison, James P.

    2007-01-01

    The progression of a productive immune response requires that a number of immunological checkpoints be passed. Passage may require the presence of excitatory costimulatory signals or the avoidance of negative or coinhibitory signals, which act to dampen or terminate immune activity. The immunoglobulin superfamily occupies a central importance in this coordination of immune responses, and the CD28/cytotoxic T-lymphocyte antigen-4 (CTLA-4):B7.1/B7.2 receptor/ligand grouping represents the archetypal example of these immune regulators. In part the role of these checkpoints is to guard against the possibility of unwanted and harmful self-directed activities. While this is a necessary function, aiding in the prevention of autoimmunity, it may act as a barrier to successful immunotherapies aimed at targeting malignant self-cells that largely display the same array of surface molecules as the cells from which they derive. Therapies aimed at overcoming these mechanisms of peripheral tolerance, in particular by blocking the inhibitory checkpoints, offer the potential to generate antitumor activity, either as monotherapies or in synergism with other therapies that directly or indirectly enhance presentation of tumor epitopes to the immune system. Such immunological molecular adjuvants are showing promise in early clinical trials. This review focuses on the results of the archetypal example of checkpoint blockade, anti-CTLA-4, in preclinical tumor models and clinical trials, while also highlighting other possible targets for immunological checkpoint blockade. PMID:16730267

  10. Research on Motion Performance of the Mobile Double-Causeway Pier System

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Mobile offshore double-causeway pier system, a type of seashore unloading equipment, consists of two groups of multiple connected semi-submersible modules. This structure has wide application because most of the middle or mini type of vessels and ships can be moored to it. Based on the analysis of computational methods of multi-body motion response, a hydrodynamic model is set up and the three-dimensional potential theory in finite depth is adopted to calculate the three-dimensional motion response of this system. The double P-M spectrum is used to analyze the motion response in irregular waves. Different wave directions are specially taken into consideration, due to their various effects to the motion response. Furthermore, the calculated result is compared with that of the experiment, and it is proved that sway, heave, pitch and yaw motion are greatly constrained by mooring system. The comparison also indicates that the model can forecast the motion performance of the target, and that the calculated result can also be used as reference in connector and mooring system design.

  11. 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...

  12. Cambridge checkpoint English workbook 1

    CERN Document Server

    Reynolds, John

    2013-01-01

    This Workbook supports our bestselling Checkpoint English series, with exercises specifically matched to the Cambridge Progression tests and the Checkpoint English tests. - Offers plenty of additional questions for use in class or as homework. - Includes clearly identified questions on grammar and punctuation, comprehension, use of language and essay planning. - Follows the structure of the relevant textbook to ensure a thorough understanding of all aspects of the course. - Provides a space for Students to write their answers. This Workbook is matched to the Cambridge Secondary 1 Curriculum Fr

  13. 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.

  14. Checkpointing for a hybrid computing node

    Energy Technology Data Exchange (ETDEWEB)

    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.

  15. Phenotypic checkpoints regulate neuronal development.

    Science.gov (United States)

    Ben-Ari, Yehezkel; Spitzer, Nicholas C

    2010-11-01

    Nervous system development proceeds by sequential gene expression mediated by cascades of transcription factors in parallel with sequences of patterned network activity driven by receptors and ion channels. These sequences are cell type- and developmental stage-dependent and modulated by paracrine actions of substances released by neurons and glia. How and to what extent these sequences interact to enable neuronal network development is not understood. Recent evidence demonstrates that CNS development requires intermediate stages of differentiation providing functional feedback that influences gene expression. We suggest that embryonic neuronal functions constitute a series of phenotypic checkpoint signatures; neurons failing to express these functions are delayed or developmentally arrested. Such checkpoints are likely to be a general feature of neuronal development and constitute presymptomatic signatures of neurological disorders when they go awry.

  16. 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

  17. CONSTRUCTION OF A CAUSEWAY BRIDGE ACROSS THE LAKE URMIA AND ITS INFLUENCE ON DRYING TREND OF THE LAKE

    Directory of Open Access Journals (Sweden)

    M. Ghadimi

    2015-12-01

    Full Text Available Construction of a causeway bridge on the Lake Urmia accelerated the drying trend of the largest hyper-saline lake of the world. The objective of the research is to investigate the differences of precipitation and river discharge before and after initiation of the construction of the bridge in 2000. The study area was the watershed of the lake. The averages of the precipitation data in the two periods before and after the project have been interpolated by IDW based on GIS Geostatistical Analyst. The two interpolated precipitation layers were used to be plugged into Student T-test equation in GIS in a spatial basis. To do this, the study area was divided to 25 regions based on drainage sub-basins. Less than 30 sample areas were randomly selected as cases from each of the regions to put into the equation. The discharge data were also compared for the two periods. The results indicated that except in some limited areas, the precipitation differences in the two periods are significant. This means that there were little changes in precipitation and river discharge in the area and consequently the drying may be caused mainly by hydrodynamic changes in the lake due to construction of the causeway. However, it can be argued that the changes in the lake’s surface area are accompanied by changes in precipitation and river discharge. The t test statistic can be applied samples based on spatial analysis.

  18. GRID COMPUTING AND CHECKPOINT APPROACH

    Directory of Open Access Journals (Sweden)

    Pankaj gupta

    2011-05-01

    Full Text Available Grid computing is a means of allocating the computational power of alarge number of computers to complex difficult computation or problem. Grid computing is a distributed computing paradigm thatdiffers from traditional distributed computing in that it is aimed toward large scale systems that even span organizational boundaries. In this paper we investigate the different techniques of fault tolerance which are used in many real time distributed systems. The main focus is on types of fault occurring in the system, fault detection techniques and the recovery techniques used. A fault can occur due to link failure, resource failure or by any other reason is to be tolerated for working the system smoothly and accurately. These faults can be detected and recovered by many techniques used accordingly. An appropriate fault detector can avoid loss due to system crash and reliable fault tolerance technique can save from system failure. This paper provides how these methods are applied to detect and tolerate faults from various Real Time Distributed Systems. The advantages of utilizing the check pointing functionality are obvious; however so far the Grid community has notdeveloped a widely accepted standard that would allow the Gridenvironment to consciously utilize low level check pointing packages.Therefore, such a standard named Grid Check pointing Architecture isbeing designed. The fault tolerance mechanism used here sets the jobcheckpoints based on the resource failure rate. If resource failureoccurs, the job is restarted from its last successful state using acheckpoint file from another grid resource. A critical aspect for anautomatic recovery is the availability of checkpoint files. A strategy to increase the availability of checkpoints is replication. Grid is a form distributed computing mainly to virtualizes and utilize geographically distributed idle resources. A grid is a distributed computational and storage environment often composed of

  19. Overlapped checkpointing with hardware assist

    Energy Technology Data Exchange (ETDEWEB)

    Mitchell, Christopher J [Los Alamos National Laboratory; Nunez, James A [Los Alamos National Laboratory; Wang, Jun [U. OF CENTRAL FLORIDA (UCF)

    2009-01-01

    We present a new approach to handling the demanding I/O workload incurred during checkpoint writes encountered in High Performance Computing. Prior efforts to improve performance have been primarily bound by mechanical limitations of the hard drive. Our research surpasses this limitation by providing a method to: (1) write checkpoint data to a high-speed, non-volatile buffer, and (2) asynchronously write this data to permanent storage while resuming computation. This removes the hard drive from the critical data path because our I/O node based buffers isolate the compute nodes from the storage servers. This solution is feasible because of industry declines in cost for high-capacity, non-volatile storage technologies. Testing was conducted on a small-scale cluster to prove the design, and then scaled at Los Alamos National Laboratory. Results show a definitive speedup factor for select workloads over writing directly to a typical global parallel file system; the Panasas ActiveScale File System.

  20. Melanoma therapy: Check the checkpoints.

    Science.gov (United States)

    Furue, Masutaka; Kadono, Takafumi

    2016-02-01

    Recent mutational and translational studies have revealed that the Ras/Raf/mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway plays a key role in melanomagenesis. Mutations in NRAS and BRAF are found in the majority of melanomas resulting in the formation of constitutively active NRAS and BRAF molecules, which leads to the proliferation and survival of melanoma cells through the activation of MEK/ERK signals. Inhibitors of BRAF or MEK significantly extend the progression-free survival and overall survival of melanoma patients compared with conventional chemotherapies. Combining BRAF and MEK inhibitors further enhances the clinical effectiveness. Cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) is an immune checkpoint molecule that downregulates T-cell activation by binding to B7 (CD80/CD86) molecules on antigen-presenting cells. Programmed death receptor ligand 1 on melanoma cells negatively regulates T-cell function by binding to the programmed death-1 (PD-1) receptor on T cells. Antibodies against CTLA-4 and PD-1 also enhance the survival of melanoma patients. In this review, we summarize the clinical effectiveness and adverse events of the BRAF inhibitors, MEK inhibitors and anti-immune checkpoint antibodies in melanoma treatment.

  1. Immigrant Nation

    Science.gov (United States)

    Hoffert, Barbara

    2008-01-01

    In an August 14, 2008 story, the New York Times reported that ethnic and racial minorities will likely be a majority of the U.S. population by 2042. Many of the blacks, Asians, Hispanics, and others constituting this emerging majority will be immigrants or the children of immigrants; the number of foreigners hitting these shores is projected to…

  2. Slipping past the spindle assembly checkpoint.

    Science.gov (United States)

    Subramanian, Radhika; Kapoor, Tarun M

    2013-11-01

    Error-free genome segregation depends on the spindle assembly checkpoint (SAC), a signalling network that delays anaphase onset until chromosomes have established proper spindle attachments. Three reports now quantitatively examine the sensitivity and robustness of the SAC response.

  3. REVIEW OF CHECKPOINTING ALGORITHMS IN DISTRIBUTED SYSTEMS

    Directory of Open Access Journals (Sweden)

    Poonam Gahlan

    2010-06-01

    Full Text Available Checkpointing is the process of saving the status information. Checkpoint is defined as a designated place in a program at which normal processing is interrupted specifically to preserve the status information necessary to allow resumption of processing at a later time. Mobile computing raises many new issues such as lack of stablestorage, low bandwidth of wireless channel, high mobility, and limited battery life. Coordinated checkpointing is an attractive approach for transparently adding fault tolerance to distributed applications since it avoids domino effects and minimizes the stable storage requirement. This paper presents the review of the algorithms,which have been reported in the literature for checkpointing. This paper also covers backward error recovery techniques for distributed systems specially the distributed mobile systems.

  4. Choreography of the 9-1-1 checkpoint complex: DDK puts a check on the checkpoints.

    Science.gov (United States)

    Paek, Andrew L; Weinert, Ted

    2010-11-24

    Checkpoint proteins respond to DNA damage by halting the cell cycle until the damage is repaired. In this issue of Molecular Cell, Furuya et al. (2010) provide evidence that checkpoint proteins need to be removed from sites of damage in order to properly repair it.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-03-20

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

  6. 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.

  7. [Foreign immigration in Spain].

    Science.gov (United States)

    Serra Yoldi, I

    1997-01-01

    This article, translated from the original Spanish, analyzes recent trends in immigration to Spain. Information is provided on annual totals of immigrants and emigrants, 1976-1991; resident foreigners by nationality, 1990-1994; resident foreigners by province and continent of origin, 1991; occupations of immigrants, 1990-1991; migrant characteristics; attitudes toward immigration; and assimilation of immigrants.

  8. A Checkpoint Storage System for Desktop Grid Computing

    CERN Document Server

    Kiswany, Samer Al; Vazhkudai, Sudharshan S

    2007-01-01

    Checkpointing is an indispensable technique to provide fault tolerance for long-running high-throughput applications like those running on desktop grids. In these environments, a checkpoint storage system can offer multiple benefits: reduce the load on a traditional file system, offer high-performance through specialization, and, finally, optimize checkpoint data management by taking into account application semantics. Such a storage system can present a unifying abstraction to checkpoint operations, while hiding the fact that there are no dedicated resources to store the checkpoint data. This paper presents a dedicated checkpoint storage system for desktop grid environments. Our solution uses scavenged disk space from participating desktops to build an inexpensive storage space, offering a traditional file system interface for easy integration with checkpointing applications. This paper presents the architecture of our checkpoint storage system, key write optimizations for high-speed I/O, support for increme...

  9. 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…

  10. User Process Checkpoint/Restart. Revision 1.1.

    Science.gov (United States)

    2007-11-02

    This document describes the design of the Tera user process checkpoint facility. Checkpoint is a means for saving the state of an executing process...or group of processes and restarting them later on demand. The motivation for providing checkpoint on the Tera is to allow long running computationally

  11. 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.

  12. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-09-01

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

  14. The spindle checkpoint and chromosome segregation in meiosis.

    Science.gov (United States)

    Gorbsky, Gary J

    2015-07-01

    The spindle checkpoint is a key regulator of chromosome segregation in mitosis and meiosis. Its function is to prevent precocious anaphase onset before chromosomes have achieved bipolar attachment to the spindle. The spindle checkpoint comprises a complex set of signaling pathways that integrate microtubule dynamics, biomechanical forces at the kinetochores, and intricate regulation of protein interactions and post-translational modifications. Historically, many key observations that gave rise to the initial concepts of the spindle checkpoint were made in meiotic systems. In contrast with mitosis, the two distinct chromosome segregation events of meiosis present a special challenge for the regulation of checkpoint signaling. Preservation of fidelity in chromosome segregation in meiosis, controlled by the spindle checkpoint, also has a significant impact in human health. This review highlights the contributions from meiotic systems in understanding the spindle checkpoint as well as the role of checkpoint signaling in controlling the complex divisions of meiosis.

  15. MOSES - Inflatable Causeway

    Science.gov (United States)

    2007-08-01

    buoyant. Kevlar and Zylon are good alternatives, but they are denser then water, hence they will not float. The draw back from Supreme Protector...Retention % (due to UV rays after 6 Months) Zylon AS 5.8 1.54 3.5 90 35 Zylon HM 5.8 1.56 2.5 N/A 35 p-Aramid 2.8 1.45 2.4 100 N/A m-Aramid...Sites. Off- Shore Air Compressors. 15 June 2007. < http://www.fas.org/man/dod-101/sys/land/index.html> Toyobo Family of Sites. Zylon Fabric. 19

  16. Targeting immune checkpoints in malignant glioma

    Science.gov (United States)

    Li, Tete; Liu, Yong-Jun; Chen, Wei; Chen, Jingtao

    2017-01-01

    Malignant glioma is the most common and a highly aggressive cancer in the central nervous system (CNS). Cancer immunotherapy, strategies to boost the bodys anti-cancer immune responses instead of directly targeting tumor cells, recently achieved great success in treating several human solid tumors. Although once considered immune privileged and devoid of normal immunological functions, CNS is now considered a promising target for cancer immunotherapy, featuring the recent progresses in neurobiology and neuroimmunology and a highly immunosuppressive state in malignant glioma. In this review, we focus on immune checkpoint inhibitors, specifically, antagonizing monoclonal antibodies for programmed cell death protein-1 (PD-1), cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), and indoleamine 2,3-dioxygenase (IDO). We discuss advances in the working mechanisms of these immune checkpoint molecules, their status in malignant glioma, and current preclinical and clinical trials targeting these molecules in malignant glioma. PMID:27756892

  17. [Cancer immunotherapy by immuno-checkpoint blockade].

    Science.gov (United States)

    Kawakami, Yutaka

    2015-10-01

    As cancer immunotherapies utilizing anti-tumor T-cell responses, immuno-checkpoint blockade and adoptive T-cell immunotherapy have recently achieved durable responses even in advanced cancer patients with metastases. Administration of antibodies on the T-cell surface, CTLA-4 and PD-1 (or PD-1 ligand PD-L1), resulted in tumor regression of not only melanoma and renal cell cancer which were known to be relatively sensitive to immunotherapy, but also various malignancies including lung, bladder, ovarian, gastric, and head and neck cancers, as well as hematological malignancies such as Hodgkin and B-cell malignant lymphomas. These findings have changed the status of immunotherapy in the development of cancer treatments. Currently, development of combinations employing cancer immunotherapy with immuno-checkpoint blockade, as well as personalized cancer immunotherapy based on the evaluation of pretreatment immune status, are in progress.

  18. Renal effects of immune checkpoint inhibitors.

    Science.gov (United States)

    Izzedine, Hassan; Mateus, Christine; Boutros, Céline; Robert, Caroline; Rouvier, Philippe; Amoura, Zahir; Mathian, Alexis

    2016-12-26

    Recent advances in immune checkpoint inhibitor (ICPI) development have led to major improvements in oncology patient outcomes. Cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programmed cell death protein 1 (PD-1) are two essential immune checkpoint receptors. Ipilimumab and tremelimumab (anti-CTLA-4-blocking antibodies) and pembrolizumab and nivolumab (antibodies targeting PD-1 receptors) have already been approved by US Food and Drug Administration in several malignancies. Two different forms of ICPI-induced renal damage have been identified, including acute (granulomatous) tubulointerstitial nephritis and immune complex glomerulonephritis. The observed acute renal damage can be reversed upon ICPI drug discontinuation and renal function can recover back to normal following the introduction of systemic corticosteroid treatment. Any delay in treating this complication could result in definitive and irreversible renal injury.

  19. Immigration and Firm Expansion

    OpenAIRE

    William W. Olney

    2008-01-01

    Research generally focuses on how immigration affects native workers, while the impact of immigration on domestic firms is often overlooked. This paper addresses this important omission by examining whether firms respond to immigration by expanding their production activities within a city in order to utilize the abundant supply of low-skilled workers. Using data on immigration and the universe of establishments in U.S. cities, the results indicate that firms respond to immigration at the ext...

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

    Science.gov (United States)

    Archer, Charles Jens; Inglett, Todd Alan

    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.

  1. Checkpointing and rollback recovery for network of workstations

    Institute of Scientific and Technical Information of China (English)

    汪东升; 郑纬民; 王鼎兴; 沈美明

    1999-01-01

    Network of workstations (NOW) now becomes one of the main trends of parallel computing. But for long-running scientific programs, it needs effective fault tolerance for its changing property. Checkpointing and rollback recovery is a solution to this problem. First the main problems upon rollback recovery are discussed, the different checkpointing techniques for NOW are analyzed, and then the design and implementation of ChaRM (checkpoint-based rollback recovery and process migration) system are described. The comparison of three coordinated checkpointing systems is given.

  2. Attitudes towards Immigration

    DEFF Research Database (Denmark)

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

    2016-01-01

    immigration: scoring higher on this trait implies a greater willingness to admit immigrants. Moreover, individuals react differently to economic threat depending on their score on the traits Agreeableness and Conscientiousness. Specifically, individuals scoring low on Agreeableness and individuals scoring...... 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....

  3. Crime and immigration

    OpenAIRE

    Bell, Brian

    2014-01-01

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

  4. Immigration and Entrepreneurship

    OpenAIRE

    Fairlie, Robert W.; Lofstrom, Magnus

    2013-01-01

    Immigrants are widely perceived as being highly entrepreneurial and important for economic growth and innovation. This is reflected in immigration policies and many developed countries have created special visas and entry requirements in an attempt to attract immigrant entrepreneurs. Not surprisingly, a large body of research on immigrant entrepreneurship has developed over the years. In this chapter we provide an overview of the economics literature with respect to some of the most fundament...

  5. Attitudes towards immigration

    DEFF Research Database (Denmark)

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

    2008-01-01

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

  6. Tactical Checkpoint: Hail/Warn Suppress/Stop (Poster)

    Science.gov (United States)

    2010-11-15

    distractor , optical suppression , human behavior, checkpoint, ambient light, driver suppression , human experimentation, light, paintball, obscuration...HAIL/WARN AND - SUPPRESS /STOP Poster Presented at the 2010 Directed Energies Professional Society Meeting, 15-19 November 2010. 5a. CONTRACT NUMBER...warning to a driver that is approaching a checkpoint. The laser, MCNC light, and the windshield obscuration were evaluated for their suppression

  7. 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...

  8. Multilingualism in Immigrant Communities

    NARCIS (Netherlands)

    Yagmur, Kutlay; Cenoz, Jasone; Gorter, Durk; May, Stephen

    2016-01-01

    Immigrant multilingualism is a very complex topic. It is at the crossroads of multiple disciplines that have fundamentally different perspectives on the topic. Depending on the ideological approach taken, immigrant multilingualism is seen either as a deficit or as a resource. Immigrant minority (IM

  9. A New Immigration Policy.

    Science.gov (United States)

    Dummett, Anne

    This book focuses on the issue of immigration to the United Kingdom (U.K.). Causes of migration, such as economic opportunities and emergency political refuge, are discussed in terms of the need for the government to devise an effective and just immigration system. Immigration laws of Norway, Sweden, Australia, Canada, and the U.K. are outlined,…

  10. Immune checkpoints in cancer clinical trials

    Institute of Scientific and Technical Information of China (English)

    Elad Sharon; Howard Streicher; Priscila Goncalves; Helen XChen

    2014-01-01

    Immunology-based therapy is rapidly developing into an effective treatment option for a surprising range of cancers. We have learned over the last decade that powerful immunologic effector cells may be blocked by inhibitory regulatory pathways controlled by specific molecules often called“immune checkpoints.” These checkpoints serve to control or turn off the immune response when it is no longer needed to prevent tissue injury and autoimmunity. Cancer cells have learned or evolved to use these mechanisms to evade immune control and elimination. The development of a new therapeutic class of drugs that inhibit these inhibitory pathways has recently emerged as a potent strategy in oncology. Three sets of agents have emerged in clinical trials exploiting this strategy. These agents are antibody-based therapies targeting cytotoxic T-lymphocyte antigen4 (CTLA4), programmed cell death1 (PD-1), and programmed cell death ligand 1 (PD-L1). These inhibitors of immune inhibition have demonstrated extensive activity as single agents and in combinations. Clinical responses have been seen in melanoma, renal cellcarcinoma, non-smal celllung cancer, and several other tumor types. Despite the autoimmune or inflammatory immune-mediated adverse effects which have been seen, the responses and overall survival benefits exhibited thus far warrant further clinical development.

  11. 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.

  12. Immigration and income inequality

    DEFF Research Database (Denmark)

    Deding, Mette; Hussain, Azhar; Jakobsen, Vibeke

    2010-01-01

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

  13. 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.

  14. Using the Sirocco File System for high-bandwidth checkpoints.

    Energy Technology Data Exchange (ETDEWEB)

    Klundt, Ruth Ann; Curry, Matthew L.; Ward, H. Lee

    2012-02-01

    The Sirocco File System, a file system for exascale under active development, is designed to allow the storage software to maximize quality of service through increased flexibility and local decision-making. By allowing the storage system to manage a range of storage targets that have varying speeds and capacities, the system can increase the speed and surety of storage to the application. We instrument CTH to use a group of RAM-based Sirocco storage servers allocated within the job as a high-performance storage tier to accept checkpoints, allowing computation to potentially continue asynchronously of checkpoint migration to slower, more permanent storage. The result is a 10-60x speedup in constructing and moving checkpoint data from the compute nodes. This demonstration of early Sirocco functionality shows a significant benefit for a real I/O workload, checkpointing, in a real application, CTH. By running Sirocco storage servers within a job as RAM-only stores, CTH was able to store checkpoints 10-60x faster than storing to PanFS, allowing the job to continue computing sooner. While this prototype did not include automatic data migration, the checkpoint was available to be pushed or pulled to disk-based storage as needed after the compute nodes continued computing. Future developments include the ability to dynamically spawn Sirocco nodes to absorb checkpoints, expanding this mechanism to other fast tiers of storage like flash memory, and sharing of dynamic Sirocco nodes between multiple jobs as needed.

  15. 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.

  16. A divergent role of the SIRT1-TopBP1 axis in regulating metabolic checkpoint and DNA damage checkpoint.

    Science.gov (United States)

    Liu, Tongzheng; Lin, Yi-Hui; Leng, Wenchuan; Jung, Sung Yun; Zhang, Haoxing; Deng, Min; Evans, Debra; Li, Yunhui; Luo, Kuntian; Qin, Bo; Qin, Jun; Yuan, Jian; Lou, Zhenkun

    2014-12-04

    DNA replication is executed only when cells have sufficient metabolic resources and undamaged DNA. Nutrient limitation and DNA damage cause a metabolic checkpoint and DNA damage checkpoint, respectively. Although SIRT1 activity is regulated by metabolic stress and DNA damage, its function in these stress-mediated checkpoints remains elusive. Here we report that the SIRT1-TopBP1 axis functions as a switch for both checkpoints. With glucose deprivation, SIRT1 is activated and deacetylates TopBP1, resulting in TopBP1-Treslin disassociation and DNA replication inhibition. Conversely, SIRT1 activity is inhibited under genotoxic stress, resulting in increased TopBP1 acetylation that is important for the TopBP1-Rad9 interaction and activation of the ATR-Chk1 pathway. Mechanistically, we showed that acetylation of TopBP1 changes the conformation of TopBP1, thereby facilitating its interaction with distinct partners in DNA replication and checkpoint activation. Taken together, our studies identify the SIRT1-TopBP1 axis as a key signaling mode in the regulation of the metabolic checkpoint and the DNA damage checkpoint.

  17. Raja Junankar, Economics of Immigration: Immigration and the Australian Economy

    OpenAIRE

    DOUGLAS, Kacey

    2016-01-01

    Abstract. The Economics of Immigration: Immigration and the Australian Economy is a compilation of academic articles written by P.N. Junankar and coauthors on the topic of immigration in Australia. From the effects of immigration on Australia’s economy to the Australian labor market environment immigrants encounter, this book addresses important questions regarding immigration that are relevant to any economy.Keywords. Australia, International migration, International economics.JEL. F00, F22,...

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

    Science.gov (United States)

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

    2010-05-01

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

  19. 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;

  20. A New Adaptive Checkpointing Strategy for Mobile Computing

    Institute of Scientific and Technical Information of China (English)

    MENChaoguang; ZUODecheng; YANGXiaozong

    2005-01-01

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

  1. Immune checkpoint receptors in regulating immune reactivity in rheumatic disease

    OpenAIRE

    Ceeraz, Sabrina; Nowak, Elizabeth C.; Burns, Christopher M.; Noelle, Randolph J.

    2014-01-01

    Immune checkpoint regulators are critical modulators of the immune system, allowing the initiation of a productive immune response and preventing the onset of autoimmunity. Co-inhibitory and co-stimulatory immune checkpoint receptors are required for full T-cell activation and effector functions such as the production of cytokines. In autoimmune rheumatic diseases, impaired tolerance leads to the development of diseases such as rheumatoid arthritis, systemic lupus erythematosus, and Sjogren’s...

  2. A survey of checkpointing algorithms for parallel and distributed computers

    Indian Academy of Sciences (India)

    S Kalaiselvi; V Rajaraman

    2000-10-01

    Checkpoint is defined as a designated place in a program at which normal processing is interrupted specifically to preserve the status information necessary to allow resumption of processing at a later time. Checkpointing is the process of saving the status information. This paper surveysthe algorithms which have been reported in the literature for checkpointing parallel/distributed systems. It has been observed that most of the algorithms published for checkpointing in message passing systems are based on the seminal article by Chandy and Lamport. A large number of articles have been published in this area by relaxing the assumptions made in this paper and by extending it to minimise the overheads of coordination and context saving. 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 in shared memory systems. They however also include methods for storing the status of distributed memory in stable storage. Most of the algorithms assume that there is no knowledge about the programs being executed.It is howeverfelt that in development of parallel programs the user has to do a fair amount of work in distributing tasks and this information can be effectively used to simplify checkpointing and rollback recovery.

  3. An Analysis of Checkpointing Algorithms for Distributed Mobile Systems

    Directory of Open Access Journals (Sweden)

    Ajay Khunteta

    2010-07-01

    Full Text Available Distributed snapshots are an important building block for distributed systems, and are useful for constructing efficient checkpointing protocols, among other uses. Direct application of these algorithms to mobile systems is not easible, however, due to differences in the environment in which mobile systems operate, relative to general distributed systems. The mobile computing environment introduces newchallenges in the area of fault-tolerant computing. Compared to traditional distributed environments, wireless networks are typically slower, providing lower throughput and latency, comparing to wireline networks. In addition, the mobile hosts have limited computation esources, are often exposed to harsh operating environment that makes them more likely to fail, and can roam while operating. Over the past two decades, intensive research work has been carried out on providing efficient checkpointing protocols in traditional distributed computing. Recently, more attention has been paid to providing checkpointing protocols for mobile systems. Some of these protocols have been adapted from the traditional distributed environment; others have been created from scratch for mobile systems. Checkpoint is defined as a designated place in a program at which normal processing is interrupted specifically to preserve the status information necessary to allow resumption of processing at alater time. Checkpointing is the process of saving the status information. This paper surveys the algorithms which have been reported in the literature for checkpointing in Mobile Distributed systems.

  4. A Tunable Checkpointing Algorithm for Distributed Mobile Applications

    Directory of Open Access Journals (Sweden)

    Sungchae Lim

    2011-11-01

    Full Text Available The aim of a distributed checkpointing algorithm is to efficiently restore the execution state of distributed applications in face of hardware or software failures. Originally, such algorithms were devised for fixed networking systems, of which computing components communicate with each other via wired networks. Therefore, those algorithms usually suffer from heavy networking costs coming from frequent data transits over wireless networks, if they are used in the wireless computing environment. In this paper, to reduce usage of wireless communications, our checkpointing algorithm allows the distributed mobile application to tune the level of its checkpointing strictness. The strictness is defined by the maximum rollback distance (MRD that says how many recent local checkpoints can be rolled back in the worst case. Since our algorithm have more flexibility in checkpointing schedule due to the use of MRD, it is possible to reduce the number of enforced local checkpointing. In particular, the amount of data transited on wirelesses networks becomes smaller than in earlier methods; thus, our algorithm provides less communication cost and shortened blocking time.

  5. The protein phosphatase 2A functions in the spindle position checkpoint by regulating the checkpoint kinase Kin4.

    Science.gov (United States)

    Chan, Leon Y; Amon, Angelika

    2009-07-15

    In budding yeast, a surveillance mechanism known as the spindle position checkpoint (SPOC) ensures accurate genome partitioning. In the event of spindle misposition, the checkpoint delays exit from mitosis by restraining the activity of the mitotic exit network (MEN). To date, the only component of the checkpoint to be identified is the protein kinase Kin4. Furthermore, how the kinase is regulated by spindle position is not known. Here, we identify the protein phosphatase 2A (PP2A) in complex with the regulatory subunit Rts1 as a component of the SPOC. Loss of PP2A-Rts1 function abrogates the SPOC but not other mitotic checkpoints. We further show that the protein phosphatase functions upstream of Kin4, regulating the kinase's phosphorylation and localization during an unperturbed cell cycle and during SPOC activation, thus defining the phosphatase as a key regulator of SPOC function.

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

    Science.gov (United States)

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

    2015-05-08

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

  7. 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…

  8. 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 b

  9. Experiences with treating immigrants

    DEFF Research Database (Denmark)

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

    2012-01-01

    sought to explore professionals' experiences of delivering care to immigrants in districts densely populated with immigrants across Europe. METHODS: Forty-eight semi-structured interviews were conducted with mental health care professionals working in 16 European countries. Professionals in each country......PURPOSE: While there has been systematic research on the experiences of immigrant patients in mental health services within certain European countries, little research has explored the experiences of mental health professionals in the delivery of services to immigrants across Europe. This study...... of marginalisation. CONCLUSIONS: Although mental health service delivery varies between and within European countries, consistent challenges exist in the experiences of mental health professionals delivering services in communities with high proportions of immigrants. Improvements to practice should include training...

  10. 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....

  11. 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...

  12. 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...... interval, CI, 1.27-8.04). Forty-two per cent (n = 35) perceived that immigrant customers put pressure on pharmacy staff resources, while 27% (n = 23) found that the immigrant customer group make work more interesting. More pharmacists than assistants agreed on the latter (OR, 3.43; 95% CI, 1...

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

    Energy Technology Data Exchange (ETDEWEB)

    Kai, Mihoko; Wang, Teresa S.-F

    2003-11-27

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

  14. Voting over Selective Immigration Policies with Immigration Aversion

    OpenAIRE

    Russo, Giuseppe

    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...

  15. 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…

  16. 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.…

  17. Immigrant Teachers in Australia

    Directory of Open Access Journals (Sweden)

    Jock Collins

    2012-11-01

    Full Text Available One of the features of contemporary society is the increasing global mobility of professionals. While the education industry is a key site of the demand for contemporary global professional migration, little attention has been given to the global circulation of education professionals. Over past decades, immigrant teachers have been an important component of skilled and professional immigration into Australia, there is no comprehensive contemporary national study of the experiences of immigrant teachers in Australia. This article aims to fill this gap and to answer questions about their decision to move to Australia, their experience with Australian Education Departments in getting appointed to a school, their experiences as teachers in the classroom and in their new Australian community. It draws on primary data sources - in the form of a survey of 269 immigrant teachers in schools in NSW, SA and WA conducted in 2008-9 - and secondary sources - in the form of the 2006 national census and Longitudinal Survey of Immigrants in Australia – to provide insights into immigrant teachers in Australian schools, adding also to our understanding of Australia’s contemporary immigration experience.

  18. 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.

  19. Immune Checkpoint Inhibitors and Prostate Cancer: A New Frontier?

    Science.gov (United States)

    Modena, Alessandra; Ciccarese, Chiara; Iacovelli, Roberto; Brunelli, Matteo; Montironi, Rodolfo; Fiorentino, Michelangelo; Tortora, Giampaolo; Massari, Francesco

    2016-01-01

    Despite recent advances in the treatment of metastatic castration-resistant 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. PMID:27471580

  20. Immune Checkpoint Inhibitors and Prostate Cancer: A New Frontier?

    Science.gov (United States)

    Modena, Alessandra; Ciccarese, Chiara; Iacovelli, Roberto; Brunelli, Matteo; Montironi, Rodolfo; Fiorentino, Michelangelo; Tortora, Giampaolo; Massari, Francesco

    2016-04-15

    Despite recent advances in the treatment of metastatic castration-resistant 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.

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

    Science.gov (United States)

    Hargrove, Paul H.; Duell, Jason C.

    2006-09-01

    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.

  2. Message Efficient Checkpointing and Rollback Recovery in Heterogeneous Mobile Networks

    Science.gov (United States)

    Jaggi, Parmeet Kaur; Singh, Awadhesh Kumar

    2016-06-01

    Heterogeneous networks provide an appealing way of expanding the computing capability of mobile networks by combining infrastructure-less mobile ad-hoc networks with the infrastructure-based cellular mobile networks. The nodes in such a network range from low-power nodes to macro base stations and thus, vary greatly in their capabilities such as computation power and battery power. The nodes are susceptible to different types of transient and permanent failures and therefore, the algorithms designed for such networks need to be fault-tolerant. The article presents a checkpointing algorithm for the rollback recovery of mobile hosts in a heterogeneous mobile network. Checkpointing is a well established approach to provide fault tolerance in static and cellular mobile distributed systems. However, the use of checkpointing for fault tolerance in a heterogeneous environment remains to be explored. The proposed protocol is based on the results of zigzag paths and zigzag cycles by Netzer-Xu. Considering the heterogeneity prevalent in the network, an uncoordinated checkpointing technique is employed. Yet, useless checkpoints are avoided without causing a high message overhead.

  3. The New Immigrant Ethic

    Institute of Scientific and Technical Information of China (English)

    Kwame; Dougan

    2011-01-01

    AMY Chua’s parenting is grounded in a fear of failure,but her authoritarian style is no more exclusively Chinese than rice is:it can be found operating, to varying degrees of rigor,in most homes of recently arrived - and relatively poor - immigrants. I call this take-no-prisoners type of parenting the "new immigrant ethic." And as a black African immigrant to the West,I overcame significant odds,odds that don’t factor in Chua’s life and her Chinese-mother parenting model.

  4. Immigration, assimilation and growth.

    Science.gov (United States)

    Durkin, J T

    1998-01-01

    "This paper analyzes the welfare effects of immigration and its subsequent effect on ethnic diversity in a model featuring human capital spillovers which depend on the degree of ethnic heterogeneity, variation rates of time preference across individuals and endogenous levels of immigration and assimilation. In the model, an increase in ethnic diversity reduces the spillovers effect for the majority. Nonetheless, immigration can be welfare improving for the majority ethnic group even if it increases the degree of diversity as long as it raises the average human capital level and/or growth rate by increasing the proportion of people with low rates of time preference."

  5. Combination Approaches with Immune-Checkpoint Blockade in Cancer Therapy

    Science.gov (United States)

    Swart, Maarten; Verbrugge, Inge; Beltman, Joost B.

    2016-01-01

    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 and programed death-1 emerged as promising strategies to activate antitumor 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 in the context of the cancer-immunity cycle, aimed at increasing response rates to the single treatments. Specifically, we discuss combinations that promote antigen release and presentation, that further amplify T cell activation, that inhibit trafficking of regulatory T cells or MSDCs, that stimulate intratumoral T cell infiltration, that increase cancer recognition by T cells, and that stimulate tumor killing. PMID:27847783

  6. Combination Approaches with Immune-Checkpoint Blockade in Cancer Therapy.

    Science.gov (United States)

    Swart, Maarten; Verbrugge, Inge; Beltman, Joost B

    2016-01-01

    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 and programed death-1 emerged as promising strategies to activate antitumor 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 in the context of the cancer-immunity cycle, aimed at increasing response rates to the single treatments. Specifically, we discuss combinations that promote antigen release and presentation, that further amplify T cell activation, that inhibit trafficking of regulatory T cells or MSDCs, that stimulate intratumoral T cell infiltration, that increase cancer recognition by T cells, and that stimulate tumor killing.

  7. Immigration Policy, Assimilation of Immigrants, and Natives' Sentiments Towards Immigrants: Evidence from 12 OECD Countries

    OpenAIRE

    Bauer, Thomas K.; Lofstrom, Magnus; Zimmermann, Klaus F.

    2001-01-01

    As in the U.S. and Canada, migration is a controversial issue in Europe. This paper explores the possibility that immigration policy may affect the labor market assimilation of immigrants and hence natives’ sentiments towards immigrants. It first reviews the assimilation literature in economics and the policy approaches taken in Europe and among the traditional immigration countries. Second, a new analysis of individual data from the OECD countries studies sentiments concerning immigration an...

  8. Immigrant Child Poverty

    DEFF Research Database (Denmark)

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

    2015-01-01

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

  9. "A Day Without Immigrants"

    DEFF Research Database (Denmark)

    Heiskanen, Benita

    2009-01-01

    Abstract This article considers the debates surrounding the "Day Without Immigrants" protests organized in major U.S. cities on 1 May 2006, prompted by H.R. 4437, the Border Protection, Anti-Terrorism, and Illegal Immigration Control Act of 2005, from the multiple perspectives of scholars, pundits......, 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...

  10. 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...

  11. Mechanisms and Components of the DNA Damage Checkpoint

    Science.gov (United States)

    2002-09-01

    Saccharomyces cerevisiae DNA damage checkpoint. Molecular Cell 9: 1055-1065. (reprint included as Appendix 2) "* Schwartz, M.F., Duong, J.K., Sun, Z., Pradhan...phosphorylation sites couple Rad53 to the Saccharomyces cerevisiae DNA damage checkpoint. Molecular Cell 9, 1055-1065. 13 Molecular Cell , Vol. 9,1055-1065...Cambridge, Massachusetts 02139. 1999), and mutation of conserved amino acids in the Molecular Cell 1056 A Rad9 B ,•o 0, 1 sitesN NC -T6 RVTQSA o- 0~ --T240

  12. IMMIGRATION, IDENTITY AND LITERATURE

    Directory of Open Access Journals (Sweden)

    Semran CENGİZ

    2010-12-01

    Full Text Available The leading problems incidental to the globalization are the immigration, the poverty, the adaptation problems of the immigrants, the identity and the cultural conflicts. The globalization actors that are transforming the whole world to a huge market, consider to commercialize the product even to the people at the other end of the world. Therefore they lay emphasis on its local identity and remark its variety as its richness. In this way the limits are easily exceeded and the consumption culture becomes available to be instilled upon even the people at the back of the beyond. However one party always wins; the more some people consume, the more some people make profit. The people who does not have any power to consume anymore, becomes the guest of the ones who get them adopt this habit and desires to receive a share from this profit.The modern world people who are not pleased with this situation, have made every effort to alienate the immigrants from the center but they could not succeed. The situation that gave rise to a conflict between parties, have also led the identity problems to occur. In the present situation, the immigrants are trying to take place in the modern world as people with hybrid identities. The music produced by the children of the immigrants with double identities, attracts attention of the world where the immigrant identity, changing its shell, promises hope as the conciliation area of the new century.

  13. 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 p...

  14. CANCER IMMUNOTHERAPY BASED ON THE BLOCKADE OF IMMUNE CHECKPOINTS

    Directory of Open Access Journals (Sweden)

    A. V. Bogolyubova

    2015-01-01

    Full Text Available Immune checkpoints represent the system of inhibitory mechanisms regulating the activation of the immune response, preventing the autoimmune processes and modulating the immune response by decreasing the immune cell-mediated damage of tissues and organs. Tumor cells may utilize these checkpoints to prevent the activation of tumor-specific lymphocytes, thereby acquiring resistance against the immune response. The blockade of inhibitory signal that is transduced in immune checkpoints leading to the reactivation of antitumor immune response is a promising method of tumor immunotherapy. Since the majority of immune checkpoints are based on the ligand-receptor interactions, one of contemporary modalities of anti-tumor therapy is based on the development of ligandor receptor-blocking therapeutic monoclonal antibodies, as well as soluble recombinant receptors capable of competing for a ligand and thereby modulating the signal transduction. In the past few years, this field of tumor immunotherapy experienced an impressive success; however, the potential tradeoff for altering of the natural suppressive mechanisms is the development of the autoimmune reactions.

  15. 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.

  16. 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.

  17. 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.

  18. Checkpoint adaptation and recovery: back with Polo after the break

    NARCIS (Netherlands)

    Vugt, M.A.T.M. van; Medema, R.H.

    2004-01-01

    S. cerevisiae cells that are unable to repair a double strand break ultimately escape the DNA damage checkpoint arrest and enter mitosis. This process called 'adaptation' depends on functional Cdc5, a Polo-like kinase, and was long thought to be limited to single-cell organisms. However, the recent

  19. Checkpoint adaptation and recovery : back with Polo after the break

    NARCIS (Netherlands)

    van Vugt, Marcel A T M; Medema, René H

    2004-01-01

    S. cerevisiae cells that are unable to repair a double strand break ultimately escape the DNA damage checkpoint arrest and enter mitosis. This process called 'adaptation' depends on functional Cdc5, a Polo-like kinase, and was long thought to be limited to single-cell organisms. However, the recent

  20. Clinical impact of checkpoint inhibitors as novel cancer therapies.

    Science.gov (United States)

    Shih, Kent; Arkenau, Hendrik-Tobias; Infante, Jeffrey R

    2014-11-01

    Immune responses are tightly regulated via signaling through numerous co-stimulatory and co-inhibitory molecules. Exploitation of these immune checkpoint pathways is one of the mechanisms by which tumors evade and/or escape the immune system. A growing understanding of the biology of immune checkpoints and tumor immunology has led to the development of monoclonal antibodies designed to target co-stimulatory and co-inhibitory molecules in order to re-engage the immune system and restore antitumor immune responses. Anti-cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) antibodies were among the first to be tested in the clinic, and ipilimumab was the first immune checkpoint inhibitor approved for an anticancer indication. Agents targeting the programmed death 1 (PD-1) pathway, either PD-1 or one of its ligands, programmed death ligand 1, are in active clinical development for numerous cancers, including advanced melanoma and lung cancer. Understanding the different mechanisms of action, safety profiles, and response patterns associated with inhibition of the CTLA-4 and PD-1 pathways may improve patient management as these therapies are moved in to the clinical practice setting and may also provide a rationale for combination therapy with different inhibitors. Additional immune checkpoint molecules with therapeutic potential, including lymphocyte activation gene-3 and glucocorticoid-induced tumor necrosis factor receptor-related gene, also have inhibitors in early stages of clinical development. Clinical responses and safety data reported to date on immune checkpoint inhibitors suggest these agents may have the potential to markedly improve outcomes for patients with cancer.

  1. The DNA damage checkpoint response to replication stress: A Game of Forks.

    Directory of Open Access Journals (Sweden)

    Rachel eJossen

    2013-03-01

    Full Text Available Conditions challenging replication fork progression, collectively referred to as replication stress, represent a major source of genomic instability and are associated to cancer onset. The replication checkpoint, a specialized branch of the DNA damage checkpoint, monitors fork problems and triggers a cellular response aimed at preserving genome integrity. Here, we review the mechanisms by which the replication checkpoint monitors and responds to replication stress, focusing on the checkpoint-mediated pathways contributing to protect replication fork integrity. We discuss how cells achieve checkpoint signaling inactivation once replication stress is overcome and how a failure to timely revert checkpoint-mediated changes in cellular physiology might impact on replication dynamics and genome integrity. We also highlight the checkpoint function as an anti-cancer barrier preventing cells malignant transformation following oncogene-induced replication stress.

  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...... "original" relationship between education and attitudes found in the literature is unlikely to reflect economic self-interest, there is considerable evidence of economic self-interest when using the more directtest....

  3. Attitudes Towards Immigration

    DEFF Research Database (Denmark)

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

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

  4. Immigrants' location preferences

    DEFF Research Database (Denmark)

    Damm, Anna Piil

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

  5. 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.

  6. 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.

  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 restrictio...

  8. 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...

  9. Academic Mobility and Immigration

    Science.gov (United States)

    Tremblay, Karine

    2005-01-01

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

  10. 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.

  11. Sister chromatid tension and the spindle assembly checkpoint.

    Science.gov (United States)

    Nezi, Luigi; Musacchio, Andrea

    2009-12-01

    The spindle assembly checkpoint (SAC) is a feedback control system that monitors the state of kinetochore/microtubule attachment during mitosis and halts cell cycle progression until all chromosomes are properly aligned at the metaphase plate. The state of chromosome-microtubule attachment is implicated as a crucial factor in the checkpoint response. On the contrary, lack of tension in the centromere-kinetochore region of sister chromatids has been shown to regulate a pathway of correction of undesired chromosome-microtubule connections, while the presence of tension is believed to promote the stabilization of attachments. We discuss how tension-sensitive phenomena, such as attachment correction and stabilization, relate to the SAC and we speculate on the existence of a single pathway linking error correction and SAC activation.

  12. Update on immune checkpoint inhibitors in gynecological cancers

    Science.gov (United States)

    2017-01-01

    In recent years, progress in our understanding of immune-modulatory signaling pathways in immune cells and the tumor microenvironment (TME) has led to rejuvenated interest in cancer immunotherapy. In particular, immunotherapy targeting the immune checkpoint receptors such as cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), programmed cell-death 1 (PD-1), and programmed cell-death ligand 1 (PD-L1) have demonstrated clinical activity in a wide variety of tumors, including gynecological cancers. This review will focus on the emerging clinical data on the therapeutic role of immune checkpoint inhibitors, and potential strategies to enhance the efficacy of this class of compounds, in the context of gynecological cancers. It is anticipated that future biomarker-directed clinical trials will provide further insights into the mechanisms underlying response and resistance to immunotherapy, and help guide our approach to designing therapeutic combinations that have the potential to enhance the benefit of immunotherapy in patients with gynecologic cancers. PMID:28028993

  13. Minimum Process Coordinated Checkpointing Scheme for Ad Hoc Networks

    CERN Document Server

    Tuli, Ruchi

    2011-01-01

    The wireless mobile ad hoc network (MANET) architecture is one consisting of a set of mobile hosts capable of communicating with each other without the assistance of base stations. This has made possible creating a mobile distributed computing environment and has also brought several new challenges in distributed protocol design. In this paper, we study a very fundamental problem, the fault tolerance problem, in a MANET environment and propose a minimum process coordinated checkpointing scheme. Since potential problems of this new environment are insufficient power and limited storage capacity, the proposed scheme tries to reduce the amount of information saved for recovery. The MANET structure used in our algorithm is hierarchical based. The scheme is based for Cluster Based Routing Protocol (CBRP) which belongs to a class of Hierarchical Reactive routing protocols. The protocol proposed by us is nonblocking coordinated checkpointing algorithm suitable for ad hoc environments. It produces a consistent set of...

  14. Checkpointing Shared Memory Programs at the Application-level

    Energy Technology Data Exchange (ETDEWEB)

    Bronevetsky, G; Schulz, M; Szwed, P; Marques, D; Pingali, K

    2004-09-08

    Trends in high-performance computing are making it necessary for long-running applications to tolerate hardware faults. The most commonly used approach is checkpoint and restart(CPR)-the state of the computation is saved periodically on disk, and when a failure occurs, the computation is restarted from the last saved state. At present, it is the responsibility of the programmer to instrument applications for CPR. Our group is investigating the use of compiler technology to instrument codes to make them self-checkpointing and self-restarting, thereby providing an automatic solution to the problem of making long-running scientific applications resilient to hardware faults. Our previous work focused on message-passing programs. In this paper, we describe such a system for shared-memory programs running on symmetric multiprocessors. The system has two components: (i)a pre-compiler for source-to-source modification of applications, and (ii) a runtime system that implements a protocol for coordinating CPR among the threads of the parallel application. For the sake of concreteness, we focus on a non-trivial subset of OpenMP that includes barriers and locks. One of the advantages of this approach is that the ability to tolerate faults becomes embedded within the application itself, so applications become self-checkpointing and self-restarting on any platform. We demonstrate this by showing that our transformed benchmarks can checkpoint and restart on three different platforms (Windows/x86, Linux/x86, and Tru64/Alpha). Our experiments show that the overhead introduced by this approach is usually quite small; they also suggest ways in which the current implementation can be tuned to reduced overheads further.

  15. Emerging role of checkpoint blockade therapy in lymphoma

    Science.gov (United States)

    Galanina, Natalie; Kline, Justin; Bishop, Michael R.

    2017-01-01

    Following the successful application of immune checkpoint blockade therapy (CBT) in refractory solid tumors, it has recently gained momentum as a promising modality in the treatment of relapsed lymphoma. This significant therapeutic advance stems from decades of research that elucidated the role of immune regulation pathways and the mechanisms by which tumors can engage these critical pathways to escape immune detection. To date, two main pathways, the cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed death 1 (PD-1), have emerged as key targets of CBT demonstrating unprecedented activity particularly in heavily pretreated relapsed/refractory Hodgkin lymphoma and some forms of non-Hodgkin disease. Herein we provide a brief discussion of checkpoint blockade in the context of lymphoma biology with a specific focus on novel checkpoint inhibitors and their therapeutic activity. We discuss current clinical trials and the landscape of CBT to underscore both the remarkable progress and foreseeable limitations of this novel treatment strategy. In particular, we build upon state-of-the-art knowledge and clinical insights gained from the early trials to review potential approaches to how CBT may be integrated with other treatment modalities, including chemoimmunotherapy to improve patient outcomes in the future. Finally, as the role of CBT evolves to potentially become a cornerstone of therapy in refractory/relapsed lymphoma, we briefly emphasize the importance of predictive biomarkers in an effort to select appropriate patients who are most likely to derive benefit from CBT. PMID:28203344

  16. 8 CFR 1003.10 - Immigration judges.

    Science.gov (United States)

    2010-01-01

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

  17. U.S. Immigration Policy and Globalization.

    Science.gov (United States)

    Martin, Philip; Martin, Susan

    2001-01-01

    Focuses on U.S. immigration, exploring global issues that affect immigration, such as: economic trends, post-cold war events, and transnationalism. Addresses legal immigration, including permanent and temporary status, refugees and asylees, unauthorized migration, integrating immigrants, and administration of immigration programs. (CMK)

  18. Portrayal of Immigrants in Newsmagazines

    Directory of Open Access Journals (Sweden)

    Goran Goldberger

    2004-03-01

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

  19. Adding immigrants to microsimulation models.

    Science.gov (United States)

    Duleep, Harriet Orcutt; Dowhan, Daniel J

    2008-01-01

    Forecasts of the financial status of Social Security's Old-Age, Survivors, and Disability Insurance (OASDI) programs and forecasts of the effects of various OASDI policy options on Americans would be improved if information about the earnings and labor force behavior of various population subgroups were included in projection models. Focusing on the projection of immigrant earnings, this article proffers a conceptual basis for incorporating immigration into microsimulation models. Key results from research on immigrant earnings, as described in the first article in this trilogy--"Research on Immigrant Earnings"--are linked to methods for forecasting individual earnings in microsimulation models. The research on immigrant earnings also inspires new methods for forecasting earnings in microsimulation models as well as the projection of immigrant emigration. Forecasting immigrant earnings and emigration is discussed in the context of a "closed system"--that is, forecasts are only made for a given population, which is represented in the base sample of the microsimulation model. The third article in our trilogy--"Incorporating Immigrant Flows into Microsimulation Models"--explores how to project immigrant earnings in the context of an "open system," which includes future immigrants.

  20. 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.

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

    Science.gov (United States)

    Besnard, Sophie; Claverie, Vincent; Blanc, Frédérique

    2015-04-01

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

  2. Fission yeast cut5 links nuclear chromatin and M phase regulator in the replication checkpoint control.

    OpenAIRE

    Saka, Y.; Fantes, P; Sutani, T; McInerny, C; Creanor, J; Yanagida, M

    1994-01-01

    Fission yeast temperature-sensitive cut5 (cell untimely torn) mutants are defective in initiation and/or elongation of DNA replication but allow mitosis and cell division at a restrictive temperature. We show that the cut5 protein (identical to rad4) (i) is an essential component of the replication checkpoint system but not the DNA damage checkpoint, and (ii) negatively regulates the activation of M phase kinase at mitotic entry. Even if the replication checkpoint has been activated previousl...

  3. McrEngine: A Scalable Checkpointing System Using Data-Aware Aggregation and Compression

    Directory of Open Access Journals (Sweden)

    Tanzima Zerin Islam

    2013-01-01

    Full Text Available High performance computing (HPC systems use checkpoint-restart to tolerate failures. Typically, applications store their states in checkpoints on a parallel file system (PFS. As applications scale up, checkpoint-restart incurs high overheads due to contention for PFS resources. The high overheads force large-scale applications to reduce checkpoint frequency, which means more compute time is lost in the event of failure. We alleviate this problem through a scalable checkpoint-restart system, mcrEngine. McrEngine aggregates checkpoints from multiple application processes with knowledge of the data semantics available through widely-used I/O libraries, e.g., HDF5 and netCDF, and compresses them. Our novel scheme improves compressibility of checkpoints up to 115% over simple concatenation and compression. Our evaluation with large-scale application checkpoints show that mcrEngine reduces checkpointing overhead by up to 87% and restart overhead by up to 62% over a baseline with no aggregation or compression.

  4. 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.

  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)

  6. 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...

  7. 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...... for Danish farms in 1980–2008 to analyze the micro-level relationship between these two developments. Farms employing immigrants tend to be both larger than and no less productive than other farms. Furthermore, an increased use of immigrants is associated with an improvement in job creation and revenue......, which at least partially seems to reflect a causal effect of immigrants....

  8. Immigrant language barriers and house prices

    OpenAIRE

    Andreas M. Fischer

    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...

  9. Attitudes toward Immigrants and Immigration Policy in United Kingdom

    Directory of Open Access Journals (Sweden)

    Viviana ANDREESCU

    2011-11-01

    Full Text Available Although recent research found substantial variation in the strength of anti-immigrant opinions across new and old countries of immigration, most studies determined that the public increasingly supports restrictive immigration policies. This paper explores several sources of attitudes toward immigrants in United Kingdom and attempts to simultaneously test some of the most important theoretical explanations of public attitudes toward immigration issues when the family immigration history is taken into account. Results are based on a quantitative analysis of data from the European Social Survey (Round 4/2008. Even if when compared to persons from families with at least one foreign-born member natives express the strongest opposition to flexible migration policies and are more likely to have negative views regarding the immigrants’ role in the British society, opinions vary significantly among groups differentiated by political preferences, socioeconomic attributes, and demographic characteristics. While for native Britons findings support the economic self-interest theory, education and social attachment (i.e., interpersonal and institutional trust appear to be the strongest predictors of positive attitudes toward immigrants and opposition to restrictive immigration policies.

  10. Greatwall and Polo-like Kinase 1 Coordinate to Promote Checkpoint Recovery*

    Science.gov (United States)

    Peng, Aimin; Wang, Ling; Fisher, Laura A.

    2011-01-01

    Checkpoint recovery upon completion of DNA repair allows the cell to return to normal cell cycle progression and is thus a crucial process that determines cell fate after DNA damage. We previously studied this process in Xenopus egg extracts and established Greatwall (Gwl) as an important regulator. Here we show that preactivated Gwl kinase can promote checkpoint recovery independently of cyclin-dependent kinase 1 (Cdk1) or Plx1 (Xenopus polo-like kinase 1), whereas depletion of Gwl from extracts exhibits no synergy with that of Plx1 in delaying checkpoint recovery, suggesting a distinct but related relationship between Gwl and Plx1. In further revealing their functional relationship, we found mutual dependence for activation of Gwl and Plx1 during checkpoint recovery, as well as their direct association. We characterized the protein association in detail and recapitulated it in vitro with purified proteins, which suggests direct interaction. Interestingly, Gwl interaction with Plx1 and its phosphorylation by Plx1 both increase at the stage of checkpoint recovery. More importantly, Plx1-mediated phosphorylation renders Gwl more efficient in promoting checkpoint recovery, suggesting a functional involvement of such regulation in the recovery process. Finally, we report an indirect regulatory mechanism involving Aurora A that may account for Gwl-dependent regulation of Plx1 during checkpoint recovery. Our results thus reveal novel mechanisms underlying the involvement of Gwl in checkpoint recovery, in particular, its functional relationship with Plx1, a well characterized regulator of checkpoint recovery. Coordinated interplays between Plx1 and Gwl are required for reactivation of these kinases from the G2/M DNA damage checkpoint and efficient checkpoint recovery. PMID:21708943

  11. Monitoring spindle orientation: Spindle position checkpoint in charge

    Directory of Open Access Journals (Sweden)

    Pereira Gislene

    2010-12-01

    Full Text Available Abstract Every cell division in budding yeast is inherently asymmetric and counts on the correct positioning of the mitotic spindle along the mother-daughter polarity axis for faithful chromosome segregation. A surveillance mechanism named the spindle position checkpoint (SPOC, monitors the orientation of the mitotic spindle and prevents cells from exiting mitosis when the spindle fails to align along the mother-daughter axis. SPOC is essential for maintenance of ploidy in budding yeast and similar mechanisms might exist in higher eukaryotes to ensure faithful asymmetric cell division. Here, we review the current model of SPOC activation and highlight the importance of protein localization and phosphorylation for SPOC function.

  12. Monitoring spindle orientation: Spindle position checkpoint in charge.

    Science.gov (United States)

    Caydasi, Ayse K; Ibrahim, Bashar; Pereira, Gislene

    2010-12-11

    Every cell division in budding yeast is inherently asymmetric and counts on the correct positioning of the mitotic spindle along the mother-daughter polarity axis for faithful chromosome segregation. A surveillance mechanism named the spindle position checkpoint (SPOC), monitors the orientation of the mitotic spindle and prevents cells from exiting mitosis when the spindle fails to align along the mother-daughter axis. SPOC is essential for maintenance of ploidy in budding yeast and similar mechanisms might exist in higher eukaryotes to ensure faithful asymmetric cell division. Here, we review the current model of SPOC activation and highlight the importance of protein localization and phosphorylation for SPOC function.

  13. Immune-Related Adverse Events Associated with Immune Checkpoint Inhibitors.

    Science.gov (United States)

    Day, Daphne; Hansen, Aaron R

    2016-12-01

    Immune checkpoint inhibitors (ICIs), including antibodies targeting cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and programmed cell death protein-1 (PD-1), have shown durable treatment responses in multiple tumor types by enhancing antitumor immunity. However, removal of self-tolerance can induce autoimmunity and produce a unique immune-driven toxicity profile, termed immune-related adverse events (irAEs). As ICIs gain approval for a growing number of indications, it is imperative clinicians increase their knowledge of and ability to manage irAEs. This review examines the etiology, presentation, kinetics, and treatment of irAEs and aims to provide practical guidance for clinicians.

  14. Immigrant Education: A Fact Sheet.

    Science.gov (United States)

    Aleman, Steven R.

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

  15. 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...

  16. 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…

  17. 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 over...

  18. 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.

  19. Immigration, ethnicity, and the pandemic.

    Science.gov (United States)

    Kraut, Alan M

    2010-04-01

    The influenza pandemic of 1918-1919 coincided with a major wave of immigration to the United States. More than 23.5 million newcomers arrived between 1880 and the 1920s, mostly from Southern and Eastern Europe, Asia, Canada, and Mexico. During earlier epidemics, the foreign-born were often stigmatized as disease carriers whose very presence endangered their hosts. Because this influenza struck individuals of all groups and classes throughout the country, no single immigrant group was blamed, although there were many local cases of medicalized prejudice. The foreign-born needed information and assistance in coping with influenza. Among the two largest immigrant groups, Southern Italians and Eastern European Jews, immigrant physicians, community spokespeople, newspapers, and religious and fraternal groups shouldered the burden. They disseminated public health information to their respective communities in culturally sensitive manners and in the languages the newcomers understood, offering crucial services to immigrants and American public health officials.

  20. 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...

  1. Polo-like kinase-1 controls proteasome-dependent degradation of claspin during checkpoint recovery

    NARCIS (Netherlands)

    Mamely, Ivan; van Vugt, Marcel A. T. M.; Smits, Veronique A. J.; Semple, Jennifer I.; Lemmens, Bennie; Perrakis, Anastassis; Medema, Rene H.; Freire, Raimundo

    2006-01-01

    DNA-damage checkpoints maintain genomic integrity by mediating a cell-cycle delay in response to genotoxic stress or stalled replication forks. In response to damage, the checkpoint kinase ATR phosphorylates and activates its effector kinase Chk1 in a process that critically depends on Claspin [1].

  2. Determinants of mitotic catastrophe on abrogation of the G2 DNA damage checkpoint by UCN-01.

    Science.gov (United States)

    On, Kin Fan; Chen, Yue; Ma, Hoi Tang; Chow, Jeremy P H; Poon, Randy Y C

    2011-05-01

    Genotoxic stress such as ionizing radiation halts entry into mitosis by activation of the G(2) DNA damage checkpoint. The CHK1 inhibitor 7-hydroxystaurosporine (UCN-01) can bypass the checkpoint and induce unscheduled mitosis in irradiated cells. Precisely, how cells behave following checkpoint abrogation remains to be defined. In this study, we tracked the fates of individual cells after checkpoint abrogation, focusing in particular on whether they undergo mitotic catastrophe. Surprisingly, while a subset of UCN-01-treated cells were immediately eliminated during the first mitosis after checkpoint abrogation, about half remained viable and progressed into G(1). Both the delay of mitotic entry and the level of mitotic catastrophe were dependent on the dose of radiation. Although the level of mitotic catastrophe was specific for different cell lines, it could be promoted by extending the mitosis. In supporting this idea, weakening of the spindle-assembly checkpoint, by either depleting MAD2 or overexpressing the MAD2-binding protein p31(comet), suppressed mitotic catastrophe. Conversely, delaying of mitotic exit by depleting either p31(comet) or CDC20 tipped the balance toward mitotic catastrophe. These results underscore the interplay between the level of DNA damage and the effectiveness of the spindle-assembly checkpoint in determining whether checkpoint-abrogated cells are eliminated during mitosis.

  3. Stable MCC binding to the APC/C is required for a functional spindle assembly checkpoint

    DEFF Research Database (Denmark)

    Hein, Jamin B; Nilsson, Jakob

    2014-01-01

    The spindle assembly checkpoint (SAC) delays progression into anaphase until all chromosomes have aligned on the metaphase plate by inhibiting Cdc20, the mitotic co-activator of the APC/C. Mad2 and BubR1 bind and inhibit Cdc20, thereby forming the mitotic checkpoint complex (MCC), which can bind...

  4. 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 anaphase

  5. 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…

  6. Centrosome-associated regulators of the G2/M checkpoint as targets for cancer therapy

    Directory of Open Access Journals (Sweden)

    Broaddus Russell R

    2009-02-01

    Full Text Available Abstract In eukaryotic cells, control mechanisms have developed that restrain cell-cycle transitions in response to stress. These regulatory pathways are termed cell-cycle checkpoints. The G2/M checkpoint prevents cells from entering mitosis when DNA is damaged in order to afford these cells an opportunity to repair the damaged DNA before propagating genetic defects to the daughter cells. If the damage is irreparable, checkpoint signaling might activate pathways that lead to apoptosis. Since alteration of cell-cycle control is a hallmark of tumorigenesis, cell-cycle regulators represent potential targets for therapy. The centrosome has recently come into focus as a critical cellular organelle that integrates G2/M checkpoint control and repairs signals in response to DNA damage. A growing number of G2/M checkpoint regulators have been found in the centrosome, suggesting that centrosome has an important role in G2/M checkpoint function. In this review, we discuss centrosome-associated regulators of the G2/M checkpoint, the dysregulation of this checkpoint in cancer, and potential candidate targets for cancer therapy.

  7. Molecular Pathways: Immune Checkpoint Antibodies and their Toxicities.

    Science.gov (United States)

    Cousin, Sophie; Italiano, Antoine

    2016-09-15

    The emergence of immune checkpoint inhibitors for solid tumor treatments represents a major oncologic advance. Since the approval of ipilimumab, a cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) antibody, for the treatment of metastatic melanoma, many drugs, especially those targeting PD-1/PD-L1, have demonstrated promising antitumor effects in many types of cancer. By reactivating the immune system, these immunotherapies have led to the development of new toxicity profiles, also called immune-related adverse events (irAE). IrAEs can involve many organ systems, and their management is radically different from that of cytotoxic drugs; irAEs require immunosuppressive treatments, such as corticoids or TNFα antibody. In addition, the occurrence of irAEs has raised significant questions. Here, we summarize progress that has been made toward answering these questions, focusing on (i) the impact of immunotherapy dose on irAE occurrence, (ii) the correlation between irAE and patient outcome, (iii) the safety of immune checkpoint inhibitors in patients already treated for autoimmune disease, and (iv) the suspected effect on tumor growth of steroids used for the management of irAEs. Clin Cancer Res; 22(18); 4550-5. ©2016 AACR.

  8. Immunotherapy comes of age: Immune aging & checkpoint inhibitors.

    Science.gov (United States)

    Elias, Rawad; Karantanos, Theodoros; Sira, Elizabeth; Hartshorn, Kevan L

    2017-02-17

    Immune checkpoint inhibitors (ICIs) are based on the understanding that there are multilayered checks and balances which can be manipulated to unleash already existing, but paralyzed, immune responses to cancer. These agents are safer and more efficacious than classic cytotoxic drugs making them a very attractive therapeutic option, especially in older adults. Current available data do not suggest significant age-associated differences in the clinical profile of ICIs. It must be noted, however, that there is still relatively little information on the use of ICIs in adults over 75years of age and aging is associated with a decline in the immune system or "immunosenescence" which theoretically can reduce the efficacy of these immune based therapies. In this paper, we review the mechanism of action of ICIs, current clinical data on their use in older adults, and age-associated immune changes that might have a direct impact on their activity in this population. We chose to focus on mainly adaptive cellular immunity, and especially on components of the immune system that are implicated directly in the immune checkpoint process.

  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. Spindle assembly checkpoint and its regulators in meiosis.

    Science.gov (United States)

    Sun, Shao-Chen; Kim, Nam-Hyung

    2012-01-01

    BACKGROUND Meiosis is a unique form of cell division in which cells divide twice but DNA is duplicated only once. Errors in chromosome segregation during meiosis will result in aneuploidy, followed by loss of the conceptus during pregnancy or birth defects. During mitosis, cells utilize a mechanism called the spindle assembly checkpoint (SAC) to ensure faithful chromosome segregation. A similar mechanism has been uncovered for meiosis in the last decade, especially in the past several years. METHODS For this review, we included data and relevant information obtained through a PubMed database search for all articles published in English from 1991 through 2011 which included the term 'meiosis', 'spindle assembly checkpoint', or 'SAC'. RESULTS There are 91 studies included. Evidence for the existence of SAC functions in meiosis is provided by studies on the SAC proteins mitotic-arrest deficient-1 (Mad1), Mad2, budding uninhibited by benzimidazole-1 (Bub1), Bub3, BubR1 and Mps1; microtubule-kinetochore attachment regulators Ndc80 complex, chromosomal passenger complex, mitotic centromere-associated kinesin (MCAK), kinetochore null 1 (KNL1) and Mis12 complex and spindle stability regulators. CONCLUSIONS SAC and its regulators exist and function in meiosis, and their malfunctions may cause germ cell aneuploidy. However, species and sexual differences exist. Moreover, interaction of SAC components with other regulators is still poorly understood, which needs further study.

  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. 8 CFR 1240.1 - Immigration judges.

    Science.gov (United States)

    2010-01-01

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

  13. 8 CFR 1240.41 - Immigration judges.

    Science.gov (United States)

    2010-01-01

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

  14. 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.

  15. 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

  16. 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.

  17. 78 FR 31398 - Visas: Documentation of Immigrants Under the Immigration and Nationality Act, as Amended

    Science.gov (United States)

    2013-05-24

    ... 8332] Visas: Documentation of Immigrants Under the Immigration and Nationality Act, as Amended AGENCY..., 22 CFR part 42 is amended as follows: PART 42--VISAS: DOCUMENTATION OF IMMIGRANTS UNDER...

  18. Fueling the engine and releasing the break:combinational therapy of cancer vaccines and immune checkpoint inhibitors

    Institute of Scientific and Technical Information of China (English)

    Jennifer Kleponis; Richard Skelton; Lei Zheng

    2015-01-01

    Immune checkpoint inhibitors are increasingly drawing much attention in the therapeutic development for cancer treatment. However, many cancer patients do not respond to treatments with immune checkpoint inhibitors, partly because of the lack of tumor-inifltrating effector T cells. Cancer vaccines may prime patients for treatments with immune checkpoint inhibitors by inducing effector T-cell infiltration into the tumors and immune checkpoint signals. The combination of cancer vaccine and an immune checkpoint inhibitor may function synergistically to induce more effective antitumor immune responses, and clinical trials to test the combination are currently ongoing.

  19. 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...

  20. Checkpoint Blockade in Cancer Immunotherapy: Squaring the Circle

    Directory of Open Access Journals (Sweden)

    Maria A.V. Marzolini

    2015-03-01

    Full Text Available Manipulating the complex interaction between the immune system and tumour cells has been the focus of cancer research for many years, but it is only in the past decade that significant progress has been made in the field of cancer immunotherapy resulting in clinically effective treatments. The blockade of co-inhibitory immune checkpoints, essential for maintaining lymphocyte homeostasis and self-tolerance, by immunomodulatory monoclonal antibodies has resulted in the augmentation of anti-tumour responses. The greatest successes so far have been seen with the blockade of cytotoxic T lymphocyte associated antigen-4, which has resulted in the first Phase III clinical trial showing an overall survival benefit in metastatic melanoma, and in the blockade of the programmed cell death protein-1 axis. This concise review will focus on the clinical advances made by the blockade of these two pathways and their role in current cancer treatment strategies.

  1. Probabilistic Checkpointing Protocol to Sensor Network Fault-Tolerant

    Directory of Open Access Journals (Sweden)

    Titouna Faiza

    2012-09-01

    Full Text Available A wireless sensor network WSN is a collection of autonomous sensors nodes organized into a cooperative network. A sensor node transmits the data quantity to the sink. Indeed, a failed sink may abort the overall mission of the network. Due to their crucial functions, sinks must be designed and maintained to be robust enough in order to face trouble coming from the harsh environment. Thus, as a keystone of a WSN, a sink has to be provided with ability to recover from failures. In this paper, we propose a new protocol avoiding to the sink to be a central point of failure. First, we model a sensor node failure estimation problem through a causal network. Then, we show how the checkpointing process ensures the recovery of the network. This approach reduces both energy consumption and communication bandwidth requirements, and prolongs the lifetime of WSN. Interesting results are given by simulation

  2. 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

  3. Immigration and Muslim Immigrants: A Comparative Analysis of European States

    Directory of Open Access Journals (Sweden)

    Natasha T. Duncan

    2011-10-01

    Full Text Available Immigration policies serve a number of functions for states. Governments may use policies as instruments of foreign policy, economic growth, population growth, and/ or national security. In this post-September 11, 2001 global environment, integration policies have become more assimilationist and immigration restrictions toward nationals from Muslim countries of origin have increased in the name of national security. While this trend is common among many Western states, Britain’s immigration stance toward Muslim migrants remains unchanged. This study examines changes in policies toward immigrants—changes that make these policies de facto immigration policies though they may not have been conceived as such—in the Netherlands, Germany, France, and the absence of this change in the UK. It seeks to answer the question: what explains reforms in the Netherlands, Germany, and France while British immigration policy remained unchanged? In this effort, the article emphasizes the impact of these changes on potential migrants from predominantly Muslim countries of origin. Based on a comparative case study analysis using process tracing, findings indicate that Dutch immigration/integration policy choices influence government policy changes in other West European countries. Through a learning process, governments experiencing similar socio-political challenges observe overlapping societal responses to them and optimize in creating policy alternatives by using short-cuts and adopting policies implemented in comparable states and situations.

  4. Evidence that Aurora B is implicated in spindle checkpoint signalling independently of error correction.

    Science.gov (United States)

    Santaguida, Stefano; Vernieri, Claudio; Villa, Fabrizio; Ciliberto, Andrea; Musacchio, Andrea

    2011-04-20

    Fidelity of chromosome segregation is ensured by a tension-dependent error correction system that prevents stabilization of incorrect chromosome-microtubule attachments. Unattached or incorrectly attached chromosomes also activate the spindle assembly checkpoint, thus delaying mitotic exit until all chromosomes are bioriented. The Aurora B kinase is widely recognized as a component of error correction. Conversely, its role in the checkpoint is controversial. Here, we report an analysis of the role of Aurora B in the spindle checkpoint under conditions believed to uncouple the effects of Aurora B inhibition on the checkpoint from those on error correction. Partial inhibition of several checkpoint and kinetochore components, including Mps1 and Ndc80, strongly synergizes with inhibition of Aurora B activity and dramatically affects the ability of cells to arrest in mitosis in the presence of spindle poisons. Thus, Aurora B might contribute to spindle checkpoint signalling independently of error correction. Our results support a model in which Aurora B is at the apex of a signalling pyramid whose sensory apparatus promotes the concomitant activation of error correction and checkpoint signalling pathways.

  5. Performance comparison of hierarchical checkpoint protocols grid computing

    Directory of Open Access Journals (Sweden)

    Ndeye Massata NDIAYE

    2012-06-01

    Full Text Available Grid infrastructure is a large set of nodes geographically distributed and connected by a communication. In this context, fault tolerance is a necessity imposed by the distribution that poses a number of problems related to the heterogeneity of hardware, operating systems, networks, middleware, applications, the dynamic resource, the scalability, the lack of common memory, the lack of a common clock, the asynchronous communication between processes. To improve the robustness of supercomputing applications in the presence of failures, many techniques have been developed to provide resistance to these faults of the system. Fault tolerance is intended to allow the system to provide service as specified in spite of occurrences of faults. It appears as an indispensable element in distributed systems. To meet this need, several techniques have been proposed in the literature. We will study the protocols based on rollback recovery. These protocols are classified into two categories: coordinated checkpointing and rollback protocols and log-based independent checkpointing protocols or message logging protocols. However, the performance of a protocol depends on the characteristics of the system, network and applications running. Faced with the constraints of large-scale environments, many of algorithms of the literature showed inadequate. Given an application environment and a system, it is not easy to identify the recovery protocol that is most appropriate for a cluster or hierarchical environment, like grid computing. While some protocols have been used successfully in small scale, they are not suitable for use in large scale. Hence there is a need to implement these protocols in a hierarchical fashion to compare their performance in grid computing. In this paper, we propose hierarchical version of four well-known protocols. We have implemented and compare the performance of these protocols in clusters and grid computing using the Omnet++ simulator

  6. Ethanol Metabolism Activates Cell Cycle Checkpoint Kinase, Chk2

    Science.gov (United States)

    Clemens, Dahn L.; Mahan Schneider, Katrina J.; Nuss, Robert F.

    2011-01-01

    Chronic ethanol abuse results in hepatocyte injury and impairs hepatocyte replication. We have previously shown that ethanol metabolism results in cell cycle arrest at the G2/M transition, which is partially mediated by inhibitory phosphorylation of the cyclin-dependent kinase, Cdc2. To further delineate the mechanisms by which ethanol metabolism mediates this G2/M arrest, we investigated the involvement of upstream regulators of Cdc2 activity. Cdc2 is activated by the phosphatase Cdc25C. The activity of Cdc25C can, in turn, be regulated by the checkpoint kinase, Chk2, which is regulated by the kinase ataxia telangiectasia mutated (ATM). To investigate the involvement of these regulators of Cdc2 activity, VA-13 cells, which are Hep G2 cells modified to efficiently express alcohol dehydrogenase, were cultured in the presence or absence of 25 mM ethanol. Immunoblots were performed to determine the effects of ethanol metabolism on the activation of Cdc25C, Chk2, and ATM. Ethanol metabolism increased the active forms of ATM, and Chk2, as well as the phosphorylated form of Cdc25C. Additionally, inhibition of ATM resulted in approximately 50% of the cells being rescued from the G2/M cell cycle arrest, and ameliorated the inhibitory phosphorylation of Cdc2. Our findings demonstrate that ethanol metabolism activates ATM. ATM can activate the checkpoint kinase Chk2, resulting in phosphorylation of Cdc25C, and ultimately in the accumulation of inactive Cdc2. This may, in part, explain the ethanol metabolism-mediated impairment in hepatocyte replication, which may be important in the initiation and progression of alcoholic liver injury. PMID:21924579

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

    Science.gov (United States)

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

    2009-01-01

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

  8. [Immigration in the world economy].

    Science.gov (United States)

    Sassen, S

    1995-01-01

    "Immigration is at least partly an outcome of the actions of the governments and major private economic actors of the developed countries. The case of Japan is of interest here because it allows us to capture the intersection of economic internationalization and immigration in its inception.... This paper argues that [Japan's] new immigration is part of the globalisation of [its] economy. Japan is a major presence in a regional Asian economic system where it is the leading investor, foreign aid donor, and exporter of consumer goods (including cultural products). The new immigration to Japan is not unrelated to these processes of internationalization. Internationalization provides a context within which bridges are built with the countries of origin of potential emigrants and internationalization contributes to make the Japanese economy more porous, particularly so in the case of large cities." (EXCERPT)

  9. Immigration process in catalytic medium

    Institute of Scientific and Technical Information of China (English)

    洪文明; 王梓坤

    2000-01-01

    The longtime behavior of the immigration process associated with a catalytic super-Brown-ian motion is studied. A large number law is proved in dimension d≤3 and a central limit theorem is proved for dimension d = 3.

  10. Immigration process in catalytic medium

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    The longtime behavior of the immigration process associated with a catalytic super-Brownian motion is studied. A large number law is proved in dimension d≤3 and a central limit theorem is proved for dimension d=3.

  11. Mathematics Achievement by Immigrant Children

    Directory of Open Access Journals (Sweden)

    Gary G. Huang

    2000-05-01

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

  12. Thyroid hormone receptor interacting protein 13 (TRIP13) AAA-ATPase is a novel mitotic checkpoint-silencing protein.

    Science.gov (United States)

    Wang, Kexi; Sturt-Gillespie, Brianne; Hittle, James C; Macdonald, Dawn; Chan, Gordon K; Yen, Tim J; Liu, Song-Tao

    2014-08-22

    The mitotic checkpoint (or spindle assembly checkpoint) is a fail-safe mechanism to prevent chromosome missegregation by delaying anaphase onset in the presence of defective kinetochore-microtubule attachment. The target of the checkpoint is the E3 ubiquitin ligase anaphase-promoting complex/cyclosome. Once all chromosomes are properly attached and bioriented at the metaphase plate, the checkpoint needs to be silenced. Previously, we and others have reported that TRIP13 AAA-ATPase binds to the mitotic checkpoint-silencing protein p31(comet). Here we show that endogenous TRIP13 localizes to kinetochores. TRIP13 knockdown delays metaphase-to-anaphase transition. The delay is caused by prolonged presence of the effector for the checkpoint, the mitotic checkpoint complex, and its association and inhibition of the anaphase-promoting complex/cyclosome. These results suggest that TRIP13 is a novel mitotic checkpoint-silencing protein. The ATPase activity of TRIP13 is essential for its checkpoint function, and interference with TRIP13 abolished p31(comet)-mediated mitotic checkpoint silencing. TRIP13 overexpression is a hallmark of cancer cells showing chromosomal instability, particularly in certain breast cancers with poor prognosis. We suggest that premature mitotic checkpoint silencing triggered by TRIP13 overexpression may promote cancer development.

  13. Foreign female immigrants in Greece

    OpenAIRE

    Fakiolas, Rossetos

    2000-01-01

    Strong push, pull and network formation factors account for the over 600,000 foreign immigrants, mostly economic and with irregular status, who have been since the early 1990s in Greece, a traditionally emigration country. Over a quarter of them are females who have come alone, marking the new trend in female migration. And like their male counterparts, they find jobs due to their wage and job flexibility. The recent Greek policy to regularise irregular or undocumented immigrants (UI), that i...

  14. Economic Integration of Immigrant Entrepreneurs

    OpenAIRE

    2016-01-01

    Objective: This study investigates economic integration of immigrant entrepreneurs by comparing them with their native-born counterparts, and examines whether and how entrepreneurs’ socio-cultural integration affects their economic integration. Research Design & Methods: This study is based on data of the Social Surveys conducted by the Israeli Central Bureau of Statistics in 2008, 2010 and 2012. The sample included 1133 native-born and 576 immigrant entrepreneurs. Findings: :Socio-cultural i...

  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. Chinese Immigrant Wealth: Heterogeneity in Adaptation

    Science.gov (United States)

    Agius Vallejo, Jody; Aronson, Brian

    2016-01-01

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

  17. Incorporating immigrant flows into microsimulation models.

    Science.gov (United States)

    Duleep, Harriet Orcutt; Dowhan, Daniel J

    2008-01-01

    Building on the research on immigrant earnings reviewed in the first article of this series, "Research on Immigrant Earnings," the preceding article, "Adding Immigrants to Microsimulation Models," linked research results to various issues essential for incorporating immigrant earnings into microsimulation models. The discussions of that article were in terms of a closed system. That is, it examined a system in which immigrant earnings and emigration are forecast for a given population represented in the base sample in the microsimulation model. This article, the last in the series, addresses immigrant earnings projections for open systems--microsimulation models that include projections of future immigration. The article suggests a simple method to project future immigrants and their earnings. Including the future flow of immigrants in microsimulation models can dramatically affect the projected Social Security benefits of some groups.

  18. 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.

  19. Immigration Ethnic Diversity and Political Outcomes

    DEFF Research Database (Denmark)

    Harmon, Nikolaj Arpe

    2017-01-01

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

  20. 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.

  1. 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.

  2. Mechanism-driven biomarkers to guide immune checkpoint blockade in cancer therapy

    Science.gov (United States)

    Topalian, Suzanne L.; Taube, Janis M.; Anders, Robert A.; Pardoll, Drew M.

    2017-01-01

    With recent approvals for multiple therapeutic antibodies that block cytotoxic T lymphocyte associated antigen 4 (CTLA4) and programmed cell death protein 1 (PD1) in melanoma, non-small-cell lung cancer and kidney cancer, and additional immune checkpoints being targeted clinically, many questions still remain regarding the optimal use of drugs that block these checkpoint pathways. Defining biomarkers that predict therapeutic effects and adverse events is a crucial mandate, highlighted by recent approvals for two PDL1 diagnostic tests. Here, we discuss biomarkers for anti-PD1 therapy based on immunological, genetic and virological criteria. The unique biology of the CTLA4 immune checkpoint, compared with PD1, requires a different approach to biomarker development. Mechanism-based insights from such studies may guide the design of synergistic treatment combinations based on immune checkpoint blockade. PMID:27079802

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

    Science.gov (United States)

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

    2002-01-01

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

  4. 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......, causes impaired S-phase progression and the persistence of abnormal DNA structures (X-shaped DNA molecules) after exposure to methylmethanesulfonate. The impaired S-phase progression is due to a persistent checkpoint-mediated cell cycle delay and can be overridden by addition of caffeine. Hence......, 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...

  5. 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...

  6. Evidence that Aurora B is implicated in spindle checkpoint signalling independently of error correction

    OpenAIRE

    Santaguida, Stefano; Vernieri, Claudio; Villa, Fabrizio; Ciliberto, Andrea; Musacchio, Andrea

    2011-01-01

    Fidelity of chromosome segregation is ensured by a tension-dependent error correction system that prevents stabilization of incorrect chromosome–microtubule attachments. Unattached or incorrectly attached chromosomes also activate the spindle assembly checkpoint, thus delaying mitotic exit until all chromosomes are bioriented. The Aurora B kinase is widely recognized as a component of error correction. Conversely, its role in the checkpoint is controversial. Here, we report an analysis of the...

  7. The checkpoint Saccharomyces cerevisiae Rad9 protein contains a tandem tudor domain that recognizes DNA.

    OpenAIRE

    Lancelot, Nathalie; Charier, Gaëlle; Couprie, Joël; Duband-Goulet, Isabelle; Alpha-Bazin, Béatrice; Quémeneur, Eric; Ma, Emilie; Marsolier-Kergoat, Marie-Claude; Ropars, Virginie; Charbonnier, Jean-Baptiste; Miron, Simona; Craescu, Constantin,; Callebaut, Isabelle; Gilquin, Bernard; Zinn-Justin, Sophie

    2007-01-01

    International audience; DNA damage checkpoints are signal transduction pathways that are activated after genotoxic insults to protect genomic integrity. At the site of DNA damage, 'mediator' proteins are in charge of recruiting 'signal transducers' to molecules 'sensing' the damage. Budding yeast Rad9, fission yeast Crb2 and metazoan 53BP1 are presented as mediators involved in the activation of checkpoint kinases. Here we show that, despite low sequence conservation, Rad9 exhibits a tandem t...

  8. Cambridge checkpoint maths revision guide for the Cambridge secondary 1 test

    CERN Document Server

    Smith, Alan

    2013-01-01

    With Checkpoint Maths Revision Guide for the Cambridge Secondary 1 test you can aim for the best grade with the help of relevant and accessible notes, examiner advice plus questions and answers on each key topic. - Clear explanations of every topic covered in the Cambridge Secondary 1 Checkpoint Maths syllabus. - Builds revision skills you need for success in the test. - Exam tips wirtten by test setters and examiners giving you their expert advice. This text has not been through the Cambridge endorsement process.

  9. Direct monitoring of the strand passage reaction of DNA topoisomerase II triggers checkpoint activation.

    Directory of Open Access Journals (Sweden)

    Katherine L Furniss

    Full Text Available By necessity, the ancient activity of type II topoisomerases co-evolved with the double-helical structure of DNA, at least in organisms with circular genomes. In humans, the strand passage reaction of DNA topoisomerase II (Topo II is the target of several major classes of cancer drugs which both poison Topo II and activate cell cycle checkpoint controls. It is important to know the cellular effects of molecules that target Topo II, but the mechanisms of checkpoint activation that respond to Topo II dysfunction are not well understood. Here, we provide evidence that a checkpoint mechanism monitors the strand passage reaction of Topo II. In contrast, cells do not become checkpoint arrested in the presence of the aberrant DNA topologies, such as hyper-catenation, that arise in the absence of Topo II activity. An overall reduction in Topo II activity (i.e. slow strand passage cycles does not activate the checkpoint, but specific defects in the T-segment transit step of the strand passage reaction do induce a cell cycle delay. Furthermore, the cell cycle delay depends on the divergent and catalytically inert C-terminal region of Topo II, indicating that transmission of a checkpoint signal may occur via the C-terminus. Other, well characterized, mitotic checkpoints detect DNA lesions or monitor unattached kinetochores; these defects arise via failures in a variety of cell processes. In contrast, we have described the first example of a distinct category of checkpoint mechanism that monitors the catalytic cycle of a single specific enzyme in order to determine when chromosome segregation can proceed faithfully.

  10. Greatwall and Polo-like Kinase 1 Coordinate to Promote Checkpoint Recovery*

    OpenAIRE

    Peng, Aimin; WANG Ling; Fisher, Laura A.

    2011-01-01

    Checkpoint recovery upon completion of DNA repair allows the cell to return to normal cell cycle progression and is thus a crucial process that determines cell fate after DNA damage. We previously studied this process in Xenopus egg extracts and established Greatwall (Gwl) as an important regulator. Here we show that preactivated Gwl kinase can promote checkpoint recovery independently of cyclin-dependent kinase 1 (Cdk1) or Plx1 (Xenopus polo-like kinase 1), whereas depletion of Gwl from extr...

  11. Cambridge checkpoint English revision guide for the Cambridge secondary 1 test

    CERN Document Server

    Reynolds, John

    2013-01-01

    With Checkpoint English Revision Guide for the Cambridge Secondary 1 test you can aim for the best grade with the help of relevant and accessible notes, examiner advice plus questions and answers on each key topic. - Clear explanations of every topic covered in the Cambridge Secondary 1 Checkpoint English syllabus. - Builds revision skills you need for success in the test. - Exam tips wirtten by test setters and examiners giving you their expert advice. This text has not been through the Cambridge endorsement process.

  12. A conserved checkpoint monitors meiotic chromosome synapsis inCaenorhabditis elegans

    Energy Technology Data Exchange (ETDEWEB)

    Bhalla, Needhi; Dernburg, Abby F.

    2005-07-14

    We report the discovery of a checkpoint that monitorssynapsis between homologous chromosomes to ensure accurate meioticsegregation. Oocytes containing unsynapsed chromosomes selectivelyundergo apoptosis even if agermline DNA damage checkpoint is inactivated.This culling mechanism isspecifically activated by unsynapsed pairingcenters, cis-acting chromosomesites that are also required to promotesynapsis in Caenorhabditis elegans. Apoptosis due to synaptic failurealso requires the C. elegans homolog of PCH2,a budding yeast pachytenecheckpoint gene, which suggests that this surveillance mechanism iswidely conserved.

  13. Immigration and viral hepatitis.

    Science.gov (United States)

    Sharma, Suraj; Carballo, Manuel; Feld, Jordan J; Janssen, Harry L A

    2015-08-01

    WHO estimates reveal that the global prevalence of viral hepatitis may be as high as 500 million, with an annual mortality rate of up to 1.3 million individuals. The majority of this global burden of disease is borne by nations of the developing world with high rates of vertical and iatrogenic transmission of HBV and HCV, as well as poor access to healthcare. In 2013, 3.2% of the global population (231 million individuals) migrated into a new host nation. Migrants predominantly originate from the developing countries of the south, into the developed economies of North America and Western Europe. This mass migration of individuals from areas of high-prevalence of viral hepatitis poses a unique challenge to the healthcare systems of the host nations. Due to a lack of universal standards for screening, vaccination and treatment of viral hepatitis, the burden of chronic liver disease and hepatocellular carcinoma continues to increase among migrant populations globally. Efforts to increase case identification and treatment among migrants have largely been limited to small outreach programs in urban centers, such that the majority of migrants with viral hepatitis continue to remain unaware of their infection. This review summarizes the data on prevalence of viral hepatitis and burden of chronic liver disease among migrants, current standards for screening and treatment of immigrants and refugees, and efforts to improve the identification and treatment of viral hepatitis among migrants.

  14. Cancer cells that survive checkpoint adaptation contain micronuclei that harbor damaged DNA.

    Science.gov (United States)

    Lewis, Cody W; Golsteyn, Roy M

    2016-11-16

    We have examined the relationship between checkpoint adaptation (mitosis with damaged DNA) and micronuclei. Micronuclei in cancer cells are linked to genomic change, and may induce chromothripsis (chromosome shattering). We measured the cytotoxicity of the cancer drug cisplatin in M059K (glioma fibroblasts, IC50 15 μM). Nearly 100% of M059K cells were positive for histone γH2AX staining after 48 h treatment with a cytotoxic concentration of cisplatin. The proportion of micronucleated cells, as confirmed by microscopy using DAPI and lamin A/C staining, increased from 24% to 48%, and the total micronuclei in surviving cells accumulated over time. Promoting entry into mitosis with a checkpoint inhibitor increased the number of micronuclei in cells whereas blocking checkpoint adaptation with a Cdk inhibitor reduced the number of micronuclei. Interestingly, some micronuclei underwent asynchronous DNA replication, relative to the main nuclei, as measured by deoxy-bromo-uracil (BrdU) staining. These micronuclei stained positive for histone γH2AX, which was linked to DNA replication, suggesting that micronuclei arise from checkpoint adaptation and that micronuclei may continue to damage DNA. By contrast the normal cell line WI-38 did not undergo checkpoint adaptation when treated with cisplatin and did not show changes in micronuclei number. These data reveal that the production of micronuclei by checkpoint adaptation is part of a process that contributes to genomic change.

  15. U.S. Citizenship and Immigration Services

    Science.gov (United States)

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

  16. Immigration : What About the Children and Grandchildren?

    NARCIS (Netherlands)

    Sweetman, A.; van Ours, J.C.

    2014-01-01

    Abstract: Intergenerational immigrant integration is central to the economic growth and social development of many countries whose populations comprise a substantial share of the children and grandchildren of immigrants. In addition to basic demographics, relevant economic theories and institutional

  17. Economic Integration of Immigrant Entrepreneurs

    Directory of Open Access Journals (Sweden)

    Nonna Kushnirovich

    2016-01-01

    Full Text Available Objective: This study investigates economic integration of immigrant entrepreneurs by comparing them with their native-born counterparts, and examines whether and how entrepreneurs’ socio-cultural integration affects their economic integration. Research Design & Methods: This study is based on data of the Social Surveys conducted by the Israeli Central Bureau of Statistics in 2008, 2010 and 2012. The sample included 1133 native-born and 576 immigrant entrepreneurs. Findings: :Socio-cultural integration is not necessarily associated with economic integration and a high income. Immigrants can earn the same and even more than native-born entrepreneurs do, even if they have a low level of socio-cultural integration. The impact of socio-cultural integration on immigrant entrepreneurs’ income varies by their origin. Implications & Recommendations: Understanding integration of immigrant entrepreneurs and the factors affecting their income will help policy-makers to facilitate their economic advancement. Contribution & Value Added: Based on Berry’s concept, I propose a model of entrepreneurs’ integration. The model stresses interrelations between socio-cultural and economic integration.

  18. The Divisive Threat of Immigration in Europe

    Science.gov (United States)

    2012-12-01

    Europe , immigrant children consistently underperformed in reading. This disparity suggests that immigrant children will have lower literacy rates, less...OF IMMIGRATION IN EUROPE by Andrew J. Sheehan Lars W. Lilleby December 2012 Thesis Advisor: Gordon McCormick Second Reader: Anna...COVERED Master’s Thesis 4. TITLE AND SUBTITLE The Divisive Threat of Immigration in Europe 5. FUNDING NUMBERS 6. AUTHOR(S) Lars W. Lilleby

  19. Development in Children of Immigrant Families.

    Science.gov (United States)

    Cowden, John D; Kreisler, Kelly

    2016-10-01

    Children of immigrant families experience developmental processes in the contexts of migration and settlement, presenting immigration-specific challenges. Child health providers can use awareness of the cultural-ecological model of immigrant child development to explore how acculturation, ethnic identity formation, and bilingualism affect the children and families under their care. Cross-cultural strategies for evaluating and supporting immigrant child development are presented to guide the provider in clinical interactions and community efforts.

  20. Unprotected Drosophila melanogaster telomeres activate the spindle assembly checkpoint.

    Science.gov (United States)

    Musarò, Mariarosaria; Ciapponi, Laura; Fasulo, Barbara; Gatti, Maurizio; Cenci, Giovanni

    2008-03-01

    In both yeast and mammals, uncapped telomeres activate the DNA damage response (DDR) and undergo end-to-end fusion. Previous work has shown that the Drosophila HOAP protein, encoded by the caravaggio (cav) gene, is required to prevent telomeric fusions. Here we show that HOAP-depleted telomeres activate both the DDR and the spindle assembly checkpoint (SAC). The cell cycle arrest elicited by the DDR was alleviated by mutations in mei-41 (encoding ATR), mus304 (ATRIP), grp (Chk1) and rad50 but not by mutations in tefu (ATM). The SAC was partially overridden by mutations in zw10 (also known as mit(1)15) and bubR1, and also by mutations in mei-41, mus304, rad50, grp and tefu. As expected from SAC activation, the SAC proteins Zw10, Zwilch, BubR1 and Cenp-meta (Cenp-E) accumulated at the kinetochores of cav mutant cells. Notably, BubR1 also accumulated at cav mutant telomeres in a mei-41-, mus304-, rad50-, grp- and tefu-dependent manner. Our results collectively suggest that recruitment of BubR1 by dysfunctional telomeres inhibits Cdc20-APC function, preventing the metaphase-to-anaphase transition.

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

    Science.gov (United States)

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

    2011-08-01

    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

  2. Culturally Competent Qualitative Research with Latino Immigrants

    Science.gov (United States)

    Ojeda, Lizette; Flores, Lisa Y.; Meza, Rocio Rosales; Morales, Alejandro

    2011-01-01

    This article provides recommendations for conducting culturally competent qualitative research with Latino immigrants, a historically exploited group that represents more than half of all U.S. immigrants and is continuously growing. Limited research exists on Latino immigrants despite their large presence in the United States. The authors draw…

  3. 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...

  4. 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 cha

  5. The Netherlands : Old Emigrants - Young Immigrant Country

    NARCIS (Netherlands)

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

    1999-01-01

    Since the mid 1960s the Netherlands has an immigration surplus, mainly because of manpower recruitment from Turkey and Morocco and because of immigration from the former Dutch colony of Surinam. Immigrant workers have a weak labour market position, which is mainly related to their educational level

  6. 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.

  7. Immigration and unemployment in Australia.

    Science.gov (United States)

    Tsokhas, K

    1994-01-01

    "This article is presented in two parts. The first contains a discussion of Australia's migration programme, its different categories and changes in intakes. It also deals with the contribution made by immigration to the size of the labour force.... The second part deals with the effect of immigration on the unemployment rate and concludes that its effect is negligible or, at best, slightly positive.... Against this background the paper discusses factors contributing to the employment and unemployment experience of migrants, for whom English language proficiency and the possession of recognized skills and qualifications are important in determining employability." (SUMMARY IN FRE AND SPA)

  8. bir1 deletion causes malfunction of the spindle assembly checkpoint and apoptosis in yeast

    Directory of Open Access Journals (Sweden)

    Qun eRen

    2012-08-01

    Full Text Available Cell division in yeast is a highly regulated and well studied event. Various checkpoints are placed throughout the cell cycle to ensure faithful segregation of sister chromatids. Unexpected events, such as DNA damage or oxidative stress, cause the activation of checkpoint(s and cell cycle arrest. Malfunction of the checkpoints may induce cell death. We previously showed that under oxidative stress, the budding yeast cohesin Mcd1, a homolog of human Rad21, was cleaved by the caspase-like protease Esp1. The cleaved Mcd1 C-terminal fragment was then translocated to mitochondria, causing apoptotic cell death. In the present study, we demonstrated that Bir1 plays an important role in spindle assembly checkpoint and cell death. Similar to H2O2 treatment, deletion of BIR1 using a BIR1-degron strain caused degradation of the securin Pds1, which binds and inactivates Esp1 until metaphase-anaphase transition in a normal cell cycle. BIR1 deletion caused an increase level of ROS and mis-location of Bub1, a major protein for spindle assembly checkpoint. In wild type, Bub1 was located at the kinetochores, but was primarily in the cytoplasm in bir1 deletion strain. When BIR1 was deleted, addition of nocodazole was unable to retain the Bub1 localization on kietochores, further suggesting that Bir1 is required to activate and maintain the spindle assembly checkpoint. Our study suggests that the BIR1 function in cell cycle regulation works in concert with its anti-apoptosis function.

  9. 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

  10. 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."

  11. Immigrant and refugee health: mental health conditions.

    Science.gov (United States)

    Rew, Karl T; Clarke, S Lindsey; Gossa, Weyinshet; Savin, Daniel

    2014-08-01

    Immigrants leave their homes for unfamiliar destinations in search of better lives for themselves and their families. Many immigrants experience profound loss and emotional distress as they adjust to life in different societies. Despite these challenges, the prevalence of mental health conditions among immigrants is low, whereas children of immigrants have rates equal to those of native populations. The prevalence of mental health conditions is high among refugees, who comprise a specific subgroup of immigrants who have been displaced forcibly and often have experienced severe trauma. Cultural factors, such as stigma and somatization of emotional symptoms, make it less likely that immigrants and refugees from certain groups will ever present to mental health subspecialists. Strong therapeutic relationships, cultural sensitivity, involvement of family members, judicious use of medications, and knowledge of available community resources are important tools that can aid clinicians who treat immigrants and refugees with mental health conditions.

  12. 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…

  13. Individualist America and Today's Immigrants.

    Science.gov (United States)

    Skerry, Peter

    1991-01-01

    Reviews James Fallows's "More Like Us: Making America Great Again," a book conceived while he resided in Japan. Fallows stresses the virtues of individualism and competition. He advocates workfare, education vouchers, and generous immigration levels. He pays little attention, however, to the institutions that nurture and temper individualism. (DM)

  14. Amino acids and mTOR mediate distinct metabolic checkpoints in mammalian G1 cell cycle.

    Directory of Open Access Journals (Sweden)

    Mahesh Saqcena

    Full Text Available OBJECTIVE: In multicellular organisms, cell division is regulated by growth factors (GFs. In the absence of GFs, cells exit the cell cycle at a site in G1 referred to as the restriction point (R and enter a state of quiescence known as G0. Additionally, nutrient availability impacts on G1 cell cycle progression. While there is a vast literature on G1 cell cycle progression, confusion remains - especially with regard to the temporal location of R relative to nutrient-mediated checkpoints. In this report, we have investigated the relationship between R and a series of metabolic cell cycle checkpoints that regulate passage into S-phase. METHODS: We used double-block experiments to order G1 checkpoints that monitor the presence of GFs, essential amino acids (EEAs, the conditionally essential amino acid glutamine, and inhibition of mTOR. Cell cycle progression was monitored by uptake of [(3H]-thymidine and flow cytometry, and analysis of cell cycle regulatory proteins was by Western-blot. RESULTS: We report here that the GF-mediated R can be temporally distinguished from a series of late G1 metabolic checkpoints mediated by EAAs, glutamine, and mTOR - the mammalian/mechanistic target of rapamycin. R is clearly upstream from an EAA checkpoint, which is upstream from a glutamine checkpoint. mTOR is downstream from both the amino acid checkpoints, close to S-phase. Significantly, in addition to GF autonomy, we find human cancer cells also have dysregulated metabolic checkpoints. CONCLUSION: The data provided here are consistent with a GF-dependent mid-G1 R where cells determine whether it is appropriate to divide, followed by a series of late-G1 metabolic checkpoints mediated by amino acids and mTOR where cells determine whether they have sufficient nutrients to accomplish the task. Since mTOR inhibition arrests cells the latest in G1, it is likely the final arbiter for nutrient sufficiency prior to committing to replicating the genome.

  15. The chromosomal passenger complex and the spindle assembly checkpoint: kinetochore-microtubule error correction and beyond

    Directory of Open Access Journals (Sweden)

    Maia André F

    2008-05-01

    Full Text Available Abstract During mitosis, correct bipolar chromosome attachment to the mitotic spindle is an essential prerequisite for the equal segregation of chromosomes. The spindle assembly checkpoint can prevent chromosome segregation as long as not all chromosome pairs have obtained bipolar attachment to the spindle. The chromosomal passenger complex plays a crucial role during chromosome alignment by correcting faulty chromosome-spindle interactions (e.g. attachments that do not generate tension. In the process of doing so, the chromosomal passenger complex generates unattached chromosomes, a specific situation that is known to promote checkpoint activity. However, several studies have implicated an additional, more direct role for the chromosomal passenger complex in enforcing the mitotic arrest imposed by the spindle assembly checkpoint. In this review, we discuss the different roles played by the chromosomal passenger complex in ensuring proper mitotic checkpoint function. Additionally, we discuss the possibility that besides monitoring the presence of unattached kinetochores, the spindle assembly checkpoint may also be capable of responding to chromosome-microtubule interactions that do not generate tension and we propose experimental set-ups to study this.

  16. Constitutive Mad1 targeting to kinetochores uncouples checkpoint signalling from chromosome biorientation.

    Science.gov (United States)

    Maldonado, Maria; Kapoor, Tarun M

    2011-04-01

    Accurate chromosome segregation depends on biorientation, whereby sister chromatids attach to microtubules from opposite spindle poles. The spindle-assembly checkpoint is a surveillance mechanism in eukaryotes that inhibits anaphase until all chromosomes have bioriented. In present models, the recruitment of the spindle-assembly checkpoint protein Mad2, through Mad1, to non-bioriented kinetochores is needed to stop cell-cycle progression. However, it is unknown whether Mad1-Mad2 targeting to kinetochores is sufficient to block anaphase. Furthermore, it is unclear whether regulators of biorientation (for example, Aurora kinases) have checkpoint functions downstream of Mad1-Mad2 recruitment or whether they act upstream to quench the primary error signal. Here, we engineered a Mad1 construct that localizes to bioriented kinetochores. We show that the kinetochore localization of Mad1 is sufficient for a metaphase arrest that depends on Mad1-Mad2 binding. By uncoupling the checkpoint from its primary error signal, we show that Aurora, Mps1 and BubR1 kinases, but not Polo-like kinase, are needed to maintain checkpoint arrest when Mad1 is present on kinetochores. Together, our data suggest a model in which the biorientation errors, which recruit Mad1-Mad2 to kinetochores, may be signalled not only through Mad2 template dynamics, but also through the activity of widely conserved kinases, to ensure the fidelity of cell division.

  17. The chromosomal passenger complex and the spindle assembly checkpoint: kinetochore-microtubule error correction and beyond.

    Science.gov (United States)

    Vader, Gerben; Maia, André F; Lens, Susanne Ma

    2008-05-28

    During mitosis, correct bipolar chromosome attachment to the mitotic spindle is an essential prerequisite for the equal segregation of chromosomes. The spindle assembly checkpoint can prevent chromosome segregation as long as not all chromosome pairs have obtained bipolar attachment to the spindle. The chromosomal passenger complex plays a crucial role during chromosome alignment by correcting faulty chromosome-spindle interactions (e.g. attachments that do not generate tension). In the process of doing so, the chromosomal passenger complex generates unattached chromosomes, a specific situation that is known to promote checkpoint activity. However, several studies have implicated an additional, more direct role for the chromosomal passenger complex in enforcing the mitotic arrest imposed by the spindle assembly checkpoint. In this review, we discuss the different roles played by the chromosomal passenger complex in ensuring proper mitotic checkpoint function. Additionally, we discuss the possibility that besides monitoring the presence of unattached kinetochores, the spindle assembly checkpoint may also be capable of responding to chromosome-microtubule interactions that do not generate tension and we propose experimental set-ups to study this.

  18. Effective intra-S checkpoint responses to UVC in primary human melanocytes and melanoma cell lines.

    Science.gov (United States)

    Cordeiro-Stone, Marila; McNulty, John J; Sproul, Christopher D; Chastain, Paul D; Gibbs-Flournoy, Eugene; Zhou, Yingchun; Carson, Craig; Rao, Shangbang; Mitchell, David L; Simpson, Dennis A; Thomas, Nancy E; Ibrahim, Joseph G; Kaufmann, William K

    2016-01-01

    The objective of this study was to assess potential functional attenuation or inactivation of the intra-S checkpoint during melanoma development. Proliferating cultures of skin melanocytes, fibroblasts, and melanoma cell lines were exposed to increasing fluences of UVC and intra-S checkpoint responses were quantified. Melanocytes displayed stereotypic intra-S checkpoint responses to UVC qualitatively and quantitatively equivalent to those previously demonstrated in skin fibroblasts. In comparison with fibroblasts, primary melanocytes displayed reduced UVC-induced inhibition of DNA strand growth and enhanced degradation of p21Waf1 after UVC, suggestive of enhanced bypass of UVC-induced DNA photoproducts. All nine melanoma cell lines examined, including those with activating mutations in BRAF or NRAS oncogenes, also displayed proficiency in activation of the intra-S checkpoint in response to UVC irradiation. The results indicate that bypass of oncogene-induced senescence during melanoma development was not associated with inactivation of the intra-S checkpoint response to UVC-induced DNA replication stress.

  19. Differential effect of schisandrin B stereoisomers on ATR-mediated DNA damage checkpoint signaling.

    Science.gov (United States)

    Tatewaki, Naoto; Nishida, Hiroshi; Yoshida, Masaaki; Ando, Hidehiro; Kondo, Seizo; Sakamaki, Toshiyuki; Konishi, Tetsuya

    2013-01-01

    We have previously reported that schisandrin B (SchB) is a specific inhibitor of ATR (ataxia telangiectasia and Rad-3-related) protein kinase. Since SchB consists of a mixture of its diastereomers gomisin N (GN) and γ-schisandrin (γ-Sch), the inhibitory action of SchB might result from a stereospecific interaction between one of the stereoisomers of SchB and ATR. Therefore, we investigated the effect of GN and γ-Sch on UV (UVC at 254 nm)-induced activation of DNA damage checkpoint signaling in A549 cells. UV-induced cell death (25 - 75 J/m(2)) was amplified by the presence of the diastereomers, especially GN. At the same time, GN, but not γ-Sch, inhibited the phosphorylation of checkpoint proteins such as p53, structural maintenance of chromosomes 1, and checkpoint kinase 1 in UV-irradiated cells. Moreover, GN inhibited the G2/M checkpoint during UV-induced DNA damage. The in vitro kinase activity of immunoaffinity-purified ATR was dose-dependently inhibited by GN (IC50: 7.28 μM) but not by γ-Sch. These results indicate that GN is the active component of SchB and suggest that GN inhibits the DNA damage checkpoint signaling by stereospecifically interacting with ATR.

  20. 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.

  1. Checkpoint Kinases Regulate a Global Network of Transcription Factors in Response to DNA Damage

    Directory of Open Access Journals (Sweden)

    Eric J. Jaehnig

    2013-07-01

    Full Text Available DNA damage activates checkpoint kinases that induce several downstream events, including widespread changes in transcription. However, the specific connections between the checkpoint kinases and downstream transcription factors (TFs are not well understood. Here, we integrate kinase mutant expression profiles, transcriptional regulatory interactions, and phosphoproteomics to map kinases and downstream TFs to transcriptional regulatory networks. Specifically, we investigate the role of the Saccharomyces cerevisiae checkpoint kinases (Mec1, Tel1, Chk1, Rad53, and Dun1 in the transcriptional response to DNA damage caused by methyl methanesulfonate. The result is a global kinase-TF regulatory network in which Mec1 and Tel1 signal through Rad53 to synergistically regulate the expression of more than 600 genes. This network involves at least nine TFs, many of which have Rad53-dependent phosphorylation sites, as regulators of checkpoint-kinase-dependent genes. We also identify a major DNA damage-induced transcriptional network that regulates stress response genes independently of the checkpoint kinases.

  2. 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...

  3. Immigrant health: legal tools/legal barriers.

    Science.gov (United States)

    Moua, Mee; Guerra, Fernando A; Moore, Jill D; Valdiserri, Ronald O

    2002-01-01

    The United States is a country of immigrants, our government having been formed by recent arrivals. This trend has continued throughout our history; according to the Center for Immigration Studies, more than 26 million immigrants have settled in the United States since 1970, and approximately one million new immigrants come to the United States each year. The immigrant population faces highly diverse health issues that states, cities, and counties must address, many of which pose significant legal and policy issues. Social, cultural, and linguistic factors complicate those challenges, as does the overlay of federal immigration and health policy. Two federal laws, the Welfare Reform Act of 1996 and Title VI of the federal Civil Rights Act of 1964, have affected immigrants in two very different ways. The former made it difficult for immigrants to qualify for publicly funded benefits. In contrast, Title VI made it easier for immigrants to obtain benefits by requiring federally funded service providers to offer translating services to persons with limited English language skills. Tuberculosis treatment is perhaps the most pressing health need among recent arrivals to the United States. Methods to slow down and hopefully eliminate this disease are underway, but a more comprehensive approach to not only tuberculosis but to immigrant health in general is needed. Indeed, it will benefit those directly affected by tuberculosis and will have serious implications for the entire population for generations to come.

  4. 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.

  5. Transcriptional pausing at the translation start site operates as a critical checkpoint for riboswitch regulation

    Science.gov (United States)

    Chauvier, Adrien; Picard-Jean, Frédéric; Berger-Dancause, Jean-Christophe; Bastet, Laurène; Naghdi, Mohammad Reza; Dubé, Audrey; Turcotte, Pierre; Perreault, Jonathan; Lafontaine, Daniel A.

    2017-01-01

    On the basis of nascent transcript sequencing, it has been postulated but never demonstrated that transcriptional pausing at translation start sites is important for gene regulation. Here we show that the Escherichia coli thiamin pyrophosphate (TPP) thiC riboswitch contains a regulatory pause site in the translation initiation region that acts as a checkpoint for thiC expression. By biochemically probing nascent transcription complexes halted at defined positions, we find a narrow transcriptional window for metabolite binding, in which the downstream boundary is delimited by the checkpoint. We show that transcription complexes at the regulatory pause site favour the formation of a riboswitch intramolecular lock that strongly prevents TPP binding. In contrast, cotranscriptional metabolite binding increases RNA polymerase pausing and induces Rho-dependent transcription termination at the checkpoint. Early transcriptional pausing may provide a general mechanism, whereby transient transcriptional windows directly coordinate the sensing of environmental cues and bacterial mRNA regulation. PMID:28071751

  6. Skp2 is required for Aurora B activation in cell mitosis and spindle checkpoint.

    Science.gov (United States)

    Wu, Juan; Huang, Yu-Fan; Zhou, Xin-Ke; Zhang, Wei; Lian, Yi-Fan; Lv, Xiao-Bin; Gao, Xiu-Rong; Lin, Hui-Kuan; Zeng, Yi-Xin; Huang, Jian-Qing

    2015-01-01

    The Aurora B kinase plays a critical role in cell mitosis and spindle checkpoint. Here, we showed that the ubiquitin E3-ligase protein Skp2, also as a cell-cycle regulatory protein, was required for the activation of Aurora B and its downstream protein. When we restored Skp2 knockdown Hela cells with Skp2 and Skp2-LRR E3 ligase dead mutant we found that Skp2 could rescue the defect in the activation of Aurora B, but the mutant failed to do so. Furthermore, we discovered that Skp2 could interact with Aurora B and trigger Aurora B Lysine (K) 63-linked ubiquitination. Finally, we demonstrated the essential role of Skp2 in cell mitosis progression and spindle checkpoint, which was Aurora B dependent. Our results identified a novel ubiquitinated substrate of Skp2, and also indicated that Aurora B ubiquitination might serve as an important event for Aurora B activation in cell mitosis and spindle checkpoint.

  7. Combining targeted therapy and immune checkpoint inhibitors in the treatment of metastatic melanoma

    Institute of Scientific and Technical Information of China (English)

    Teresa Kim; Rodabe N Amaria; Christine Spencer; Alexandre Reuben; Zachary A Cooper; Jennifer A Wargo

    2014-01-01

    Melanoma is the deadliest form of skin cancer and has an incidence that is rising faster than any other solid tumor. Metastatic melanoma treatment has considerably progressed in the past ifve years with the introduction of targeted therapy (BARF and MEK inhibitors) and immune checkpoint blockade (anti-CTLA4, anti-PD-1, and anti-PD-L1). However, each treatment modality has limitations. Treatment with targeted therapy has been associated with a high response rate, but with short-term responses. Conversely, treatment with immune checkpoint blockade has a lower response rate, but with long-term responses. Targeted therapy affects antitumor immunity, and synergy may exist when targeted therapy is combined with immunotherapy. hTis article presents a brief review of the rationale and evidence for the potential synergy between targeted therapy and immune checkpoint blockade. Challenges and directions for future studies are also proposed.

  8. Sustained spindle-assembly checkpoint response requires de novo transcription and translation of cyclin B1.

    Directory of Open Access Journals (Sweden)

    Ana Lúcia Mena

    Full Text Available BACKGROUND: Microtubule-targeting drugs induce mitotic delay at pro-metaphase by preventing the spindle assembly checkpoint to be satisfied. However, especially after prolonged treatments, cells can escape this arrest in a process called mitotic slippage. The mechanisms underlying the spindle assembly checkpoint and slippage are not fully understood. It has been generally accepted that during mitosis there is a temporary shutdown of high-energy-consuming processes, such as transcription and translation. However, the synthesis of specific proteins is maintained or up-regulated since protein synthesis is necessary for entry into and progression through mitosis. METHODOLOGY/PRINCIPAL FINDINGS: In this work we investigated whether the mitotic arrest caused by the mitotic checkpoint is independent of transcription and translation. By using immunofluorescent microscopy and western blotting, we demonstrate that inhibition of either of these processes induces a shortening of the mitotic arrest caused by the nocodazole treatment, and ultimately leads to mitotic slippage. Our western blotting and RTQ-PCR results show that inhibition of transcription during mitotic arrest does not affect the expression of the spindle checkpoint proteins, whereas it induces a significant decrease in the mRNA and protein levels of Cyclin B1. The exogenous expression of Cyclin B1 substantially rescued the mitotic phenotype in nocodazole cells treated with the inhibitors of transcription and translation. CONCLUSIONS/SIGNIFICANCE: This work emphasizes the importance of transcription and translation for the maintenance of the spindle assembly checkpoint, suggesting the existence of a mechanism dependent on cyclin B1 gene regulation during mitosis. We propose that continuous transcription of mitotic regulators is required to sustain the activation of the spindle assembly checkpoint.

  9. Regulation of AURORA B function by mitotic checkpoint protein MAD2.

    Science.gov (United States)

    Shandilya, Jayasha; Medler, Kathryn F; Roberts, Stefan G E

    2016-08-17

    Cell cycle checkpoint signaling stringently regulates chromosome segregation during cell division. MAD2 is one of the key components of the spindle and mitotic checkpoint complex that regulates the fidelity of cell division along with MAD1, CDC20, BUBR1, BUB3 and MAD3. MAD2 ablation leads to erroneous attachment of kinetochore-spindle fibers and defective chromosome separation. A potential role for MAD2 in the regulation of events beyond the spindle and mitotic checkpoints is not clear. Together with active spindle assembly checkpoint signaling, AURORA B kinase activity is essential for chromosome condensation as cells enter mitosis. AURORA B phosphorylates histone H3 at serine 10 and serine 28 to facilitate the formation of condensed metaphase chromosomes. In the absence of functional AURORA B cells escape mitosis despite the presence of misaligned chromosomes. In this study we report that silencing of MAD2 results in a drastic reduction of metaphase-specific histone H3 phosphorylation at serine 10 and serine 28. We demonstrate that this is due to mislocalization of AURORA B in the absence of MAD2. Conversely, overexpression of MAD2 concentrated the localization of AURORA B at the metaphase plate and caused hyper-phosphorylation of histone H3. We find that MAD1 plays a minor role in influencing the MAD2-dependent regulation of AURORA B suggesting that the effects of MAD2 on AURORA B are independent of the spindle checkpoint complex. Our findings reveal that, in addition to its role in checkpoint signaling, MAD2 ensures chromosome stability through the regulation of AURORA B.

  10. 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

    , we show that a distinct region in Bub1 mediates kinetochore localization of BubR1 through direct binding, but surprisingly removal of this region increases checkpoint strength. Our work thus uncovers how Bub1 coordinates checkpoint signalling by distinct domains for RZZ and BubR1 recruitment...

  11. "Why we stay": immigrants' motivations for remaining in communities impacted by anti-immigration policy.

    Science.gov (United States)

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

    2013-07-01

    Although restrictive immigration policy is intended to reduce incentives for unauthorized immigrants to remain in the United States, many immigrants remain in their U.S. community despite the anti-immigration climate surrounding them. This study explores motivations shaping immigrants' intentions to stay in Arizona after passage of Senate Bill 1070 in 2010, one of the most restrictive immigration policies in recent decades. We conducted three focus groups in a large metropolitan city in Arizona with Mexican immigrant parents (N = 25). Themes emerging from the focus groups described multiple and interlocking personal, family and community, and contemporary sociopolitical motivations to stay in their community, and suggest that some important motivating factors have evolved as a result of immigrants' changing environment. Implications for research and social policy reform are discussed.

  12. 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...... 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...

  13. Functions of spindle check-point and its relationship to chromosome instability

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    It is generally believed that the equal distribution of genetic materials to two daughter cells during mitosis is the key to cell health and development. During the dynamic process, spindle checkpoint plays a very important role in chromosome movements and final sister chromatid separation. The equal and precise segregation of chromosomes contributes to the genomic stability while aberrant separations result in chromosome instability that causes pathogenesis of certain diseases such as Down's syndrome and cancers. Kinetochore and its regulatory proteins consist of the spindle checkpoint and determine the spatial and temporal orders of chromosome segregation.

  14. 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...

  15. 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...

  16. Language, culture, and adaptation in immigrant children.

    Science.gov (United States)

    Toppelberg, Claudio O; Collins, Brian A

    2010-10-01

    In this article the authors discuss first why it is crucial, from a clinical and public health perspective, to better understand the development as well as risk and protection processes for the mental health of immigrant children. The authors then shift focus to the main tenet of this article, namely, that specific aspects of the dual language development of immigrant children are highly relevant to their mental health and adaptation. This argument is illustrated with empirical studies on Latino immigrant children, as they represent the majority of immigrant children in America and as a way of exemplifying the risks and circumstances that are potentially shared by other immigrant groups. Finally, the authors conceptually differentiate dual language development and its mental health impact from the dual-culture (bicultural) development and circumstance of immigrant children and their mental health impact.

  17. Immigrants in the Sexual Revolution

    DEFF Research Database (Denmark)

    Shield, Andrew DJ

    , race, and cultural difference in the women's movement. Part III focuses on immigrants and ethnic minorities in gay and lesbian 'scenes' (e.g. bars, social circles) and formal organizations in the 1960s-80s. During these decades, contact advertisements in gay and lesbian journals facilitated new......, homosexuality, pornography, adultery and divorce were challenged and reformed, in many cases in the context of intensive social movement activism. This research explores immigrants' perceptions of the dramatic changes in sexual and gender relations transforming Europe in the 1960s-80s, and the instances...... friendships, romances, housing connections, employment, and travel opportunities across both internal and external borders (e.g. inter-ethnic and international correspondence). Interviewees recount their experiences 'coming out,' moving to cities, and being 'one of the first' people of color in various gay...

  18. Forecasting the Integration of Immigrants

    CERN Document Server

    Contucci, Pierluigi; Seyedi, Seyedalireza

    2015-01-01

    This paper presents a quantitative framework for forecasting immigrant integration using immigrant density as the single driver. By comparing forecasted integration estimates based on data collected up to specific periods in time, with observed integration quantities beyond the specified period, we show that: Our forecasts are prompt-readily available after a short period of time, accurate-with a small relative error-and finally robust-able to predict integration correctly for several years to come. The research reported here proves that the proposed model of integration and its forecast framework are simple and effective tools to reduce uncertainties about how integration phenomena emerge and how they are likely to develop in response to increased migration levels in the future.

  19. 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 n...... 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....

  20. The Immigrant Wage Gap in Germany

    OpenAIRE

    Stephan L. Thomsen; Gernandt, Johannes; Aldashev, Alisher

    2008-01-01

    Immigrants consist of foreigners and citizens with migration background. We analyze the wage gap between natives and these two groups in Germany. The estimates show a substantial gap for both groups with respect to natives. Discarding immigrants who completed education abroad reduces much of the immigrants' wage gap. This implies educational attainment in Germany is an important component of economic integration and degrees obtained abroad are valued less.

  1. Immigration Adjudication Reform: The Case for Automation

    Science.gov (United States)

    2014-09-01

    Figure 1 demonstrates the general procedures for processing an immigration benefit request. 4 Border Security, Economic Opportunity, and...not been passed by Congress. An available benchmark for considering the impact of immigration reform can be found in the “Border Security, Economic ...system, “eVerify,” 334 Border Security, Economic Opportunity, and Immigration Modernization Act, S.744, 113th Cong., 1st sess. (2013). http

  2. Immigration and Outsourcing: A General Equilibrium Analysis

    OpenAIRE

    Subhayu Bandoyopadhyay; Wall, Howard J.

    2006-01-01

    This paper analyzes the issues of immigration and outsourcing in a general-equilibrium model of international factor mobility. In our model, legal immigration is controlled through a quota, while outsourcing is determined both by the firms (in response to market conditions) and through policy-imposed barriers. A loosening of the immigration quota reduces outsourcing, enriches capitalists, leads to losses for native workers, and raises national income. If the nation targets an exogenously dete...

  3. 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...... are lack of access to jobs, education and housing which explain why recent immigrants are attracted to large cities. Finally, placed refugees are sensitive to regional unemployment and some evidence of welfare seeking is presented as well....

  4. Immigration, education and native wage inequality

    OpenAIRE

    Lumpe, Christian; Weigert, Benjamin

    2010-01-01

    In this paper we analyse the effect of immigration on the labour market prospects for different skill groups among natives. We develop a model of endogenous labour supply in which immigration affects educational decisions of natives. We argue that the distributional consequences of immigration with respect to native between-skill-group inequality are ambiguous in general and crucially depend on the host country's level of educational attainment. We show that this result is robust irrespective...

  5. Immigration, Endogenous Technology Adoption and Wages

    OpenAIRE

    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 changes in skill distribution in terms of their decisions (i) to enter different industries which require the use of different technologies; (ii) to choose across technologies that differ in their ski...

  6. 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.

  7. 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…

  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. Returns to Pre-Immigration Education for Non-Western Immigrants: Why so Low?

    Science.gov (United States)

    Hardoy, Inés; Schøne, Pål

    2014-01-01

    The main purpose of this paper is to analyse the return to pre-immigration education for non-western immigrants, and explain why it is so low. Returns to one extra year of education is three times higher for ethnic Norwegians than for non-western immigrants. Using the method "Over-Required-Under" (ORU) education approach, we reveal that…

  10. 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 ap

  11. Immigration Enforcement Actions: Fiscal Year 2008

    Data.gov (United States)

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

  12. 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...

  13. 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.

  14. Immigration Enforcement Actions: Fiscal Year 2005

    Data.gov (United States)

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

  15. Immigration Enforcement Actions: Fiscal Year 2009

    Data.gov (United States)

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

  16. 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...

  17. Do Immigrants Affect Firm-Specific Wages?

    DEFF Research Database (Denmark)

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

    2012-01-01

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

  18. Immigration Enforcement Actions: Fiscal Year 2007

    Data.gov (United States)

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

  19. 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.

  20. 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.

  1. Immigrants'assimilation process in a segmented labor market

    OpenAIRE

    Rodríguez Planas, Núria; Alcobendas, Miguel Angel

    2010-01-01

    While much of the literature on immigrants' assimilation has focused on countries with a large tradition of receiving immigrants and with flexible labor markets, very little is known on how immigrants adjust to other types of host economies. With its severe dual labor market, and an unprecedented immigration boom, Spain presents a quite unique experience to analyze immigrations' assimilation process. Using data from the 2000 to 2008 Labor Force Survey, we find that immigrants are more occupat...

  2. 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...

  3. Pre- to Post-Immigration Alcohol Use Trajectories among Recent Latino Immigrants

    Science.gov (United States)

    Sanchez, Mariana; De La Rosa, Mario; Blackson, Timothy C.; Sastre, Francisco; Rojas, Patria; Li, Tan; Dillon, Frank

    2014-01-01

    The escalation of alcohol use among some Latino immigrant groups as their time in the United States increases has been well-documented. Yet, little is known about the alcohol use behaviors of Latino immigrants prior to immigration. This prospective longitudinal study examines pre- to post-immigration alcohol use trajectories among a cohort of recent Latino immigrants. Retrospective pre-immigration data were collected at baseline from a sample of 455 Cuban, South American and Central American Latinos ages 18–34 who immigrated to the U.S. less than one year prior. Two follow-up assessments (12 months apart) reported on their post-immigration alcohol use in the past 90 days. We hypothesized (a) overall declines in pre- to post-immigration alcohol among recent Latino immigrants and (b) gender/documentation specific effects, with higher rates of alcohol use among males and undocumented participants compared to their female and documented counterparts. Growth curve analyses revealed males had higher levels of pre-immigration alcohol use with steeper declines in post-immigration alcohol use compared to females. Declines in alcohol use frequency were observed for documented, but not undocumented males. No changes in pre- to post-immigration alcohol use were found for documented or undocumented females. This study contributes to the limited knowledge of pre- to post-immigration alcohol use patterns among Latinos in the United States. Future research is needed to identify social determinants associated with the alcohol use trajectories of recent Latino immigrants, as it may inform prediction, prevention, and treatment of problem-drinking behaviors among the largest and fastest growing ethnic minority in the United States. PMID:25243834

  4. Kinetochore-microtubule attachment is sufficient to satisfy the human spindle assembly checkpoint

    NARCIS (Netherlands)

    Etemad, Banafsheh; Kuijt, Timo E F; Kops, Geert J P L

    2015-01-01

    The spindle assembly checkpoint (SAC) is a genome surveillance mechanism that protects against aneuploidization. Despite profound progress on understanding mechanisms of its activation, it remains unknown what aspect of chromosome-spindle interactions is monitored by the SAC: kinetochore-microtubule

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

    DEFF Research Database (Denmark)

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

    2013-01-01

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

  6. MAP kinase meets mitosis: A role for Raf Kinase Inhibitory Protein in spindle checkpoint regulation

    Directory of Open Access Journals (Sweden)

    Rosner Marsha

    2007-01-01

    Full Text Available Abstract Raf Kinase Inhibitory Protein (RKIP is an evolutionarily conserved protein that functions as a modulator of signaling by the MAP kinase cascade. Implicated as a metastasis suppressor, Raf Kinase Inhibitory Protein depletion correlates with poor prognosis for breast, prostate and melanoma tumors but the mechanism is unknown. Recent evidence indicates that Raf Kinase Inhibitory Protein regulates the mitotic spindle assembly checkpoint by controlling Aurora B Kinase activity, and the mechanism involves Raf/MEK/ERK signaling. In contrast to elevated MAP kinase signaling during the G1, S or G2 phases of the cell cycle that activates checkpoints and induces arrest or senescence, loss of RKIP during M phase leads to bypass of the spindle assembly checkpoint and the generation of chromosomal abnormalities. These results reveal a role for Raf Kinase Inhibitory Protein and the MAP kinase cascade in ensuring the fidelity of chromosome segregation prior to cell division. Furthermore, these data highlight the need for precise titration of the MAP kinase signal to ensure the integrity of the spindle assembly process and provide a mechanism for generating genomic instability in tumors. Finally, these results raise the possibility that RKIP status in tumors could influence the efficacy of treatments such as poisons that stimulate the Aurora B-dependent spindle assembly checkpoint.

  7. The same, only different - DNA damage checkpoints and their reversal throughout the cell cycle

    NARCIS (Netherlands)

    Shaltiel, Indra A.; Krenning, Lenno; Bruinsma, Wytse; Medema, René H.

    2015-01-01

    Cell cycle checkpoints activated by DNA double-strand breaks (DSBs) are essential for the maintenance of the genomic integrity of proliferating cells. Following DNA damage, cells must detect the break and either transiently block cell cycle progression, to allow time for repair, or exit the cell cyc

  8. Restarting the cell cycle when the checkpoint comes to a halt

    NARCIS (Netherlands)

    van Vugt, Marcel A T M; Bràs, Alexandra; Medema, René H

    2005-01-01

    The DNA damage checkpoint coordinates a block in cell proliferation with the DNA repair process that follows when lesions are inflicted on the genome. However, we do not know exactly how cell division can recommence following a DNA damage-induced arrest. Recent work from our lab has identified Polo-

  9. 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...

  10. Tumor suppressor protein C53 antagonizes checkpoint kinases to promote cyclin-dependent kinase 1 activation.

    Science.gov (United States)

    Jiang, Hai; Wu, Jianchun; He, Chen; Yang, Wending; Li, Honglin

    2009-04-01

    Cyclin-dependent kinase 1 (Cdk1)/cyclin B1 complex is the driving force for mitotic entry, and its activation is tightly regulated by the G2/M checkpoint. We originally reported that a novel protein C53 (also known as Cdk5rap3 and LZAP) potentiates DNA damage-induced cell death by modulating the G2/M checkpoint. More recently, Wang et al. (2007) found that C53/LZAP may function as a tumor suppressor by way of inhibiting NF-kappaB signaling. We report here the identification of C53 protein as a novel regulator of Cdk1 activation. We found that knockdown of C53 protein causes delayed Cdk1 activation and mitotic entry. During DNA damage response, activation of checkpoint kinase 1 and 2 (Chk1 and Chk2) is partially inhibited by C53 overexpression. Intriguingly, we found that C53 interacts with Chk1 and antagonizes its function. Moreover, a portion of C53 protein is localized at the centrosome, and centrosome-targeting C53 potently promotes local Cdk1 activation. Taken together, our results strongly suggest that C53 is a novel negative regulator of checkpoint response. By counteracting Chk1, C53 promotes Cdk1 activation and mitotic entry in both unperturbed cell-cycle progression and DNA damage response.

  11. Tumor suppressor protein C53 antagonizes checkpoint kinases to promote cyclin-dependent kinase 1 activation

    Institute of Scientific and Technical Information of China (English)

    Hai Jiang; Jianchun Wu; Chen He; Wending Yang; Honglin Li

    2009-01-01

    Cyclin-dependent kinase 1 (Cdk1)/cyclin B1 complex is the driving force for mitotic entry, and its activation is tightly regulated by the G2/M checkpoint. We originally reported that a novel protein C53 (also known as Cdk5rap3 and LZAP) potentiates DNA damage-induced cell death by modulating the G2/M checkpoint. More recently, Wang et al. (2007) found that C53/LZAP may function as a tumor suppressor by way of inhibiting NF-kB signaling. We report here the identification of C53 protein as a novel regulator of Cdk1 activation. We found that knockdown of C53 protein causes delayed Cdkl activation and mitotic entry. During DNA damage response, activation of checkpoint kinase 1 and 2 (Chk1 and Chk2) is partially inhibited by C53 overexpression. Intriguingly, we found that C53 interacts with Chkl and antagonizes its function. Moreover, a portion of C53 protein is localized at the centrosome, and centrosome-targeting C53 potently promotes local Cdk1 activation. Taken together, our results strongly suggest that C53 is a novel negative regulator of checkpoint response. By counteracting Chk1, C53 promotes Cdk1 activation and mitotic entry in both unperturbed cell-cycle progression and DNA damage response.

  12. Preserved DNA Damage Checkpoint Pathway Protects against Complications in Long-Standing Type 1 Diabetes.

    Science.gov (United States)

    Bhatt, Shweta; Gupta, Manoj K; Khamaisi, Mogher; Martinez, Rachael; Gritsenko, Marina A; Wagner, Bridget K; Guye, Patrick; Busskamp, Volker; Shirakawa, Jun; Wu, Gongxiong; Liew, Chong Wee; Clauss, Therese R; Valdez, Ivan; El Ouaamari, Abdelfattah; Dirice, Ercument; Takatani, Tomozumi; Keenan, Hillary A; Smith, Richard D; Church, George; Weiss, Ron; Wagers, Amy J; Qian, Wei-Jun; King, George L; Kulkarni, Rohit N

    2015-08-04

    The mechanisms underlying the development of complications in type 1 diabetes (T1D) are poorly understood. Disease modeling of induced pluripotent stem cells (iPSCs) from patients with longstanding T1D (disease duration ≥ 50 years) with severe (Medalist +C) or absent to mild complications (Medalist -C) revealed impaired growth, reprogramming, and differentiation in Medalist +C. Genomics and proteomics analyses suggested differential regulation of DNA damage checkpoint proteins favoring protection from cellular apoptosis in Medalist -C. In silico analyses showed altered expression patterns of DNA damage checkpoint factors among the Medalist groups to be targets of miR200, whose expression was significantly elevated in Medalist +C serum. Notably, neurons differentiated from Medalist +C iPSCs exhibited enhanced susceptibility to genotoxic stress that worsened upon miR200 overexpression. Furthermore, knockdown of miR200 in Medalist +C fibroblasts and iPSCs rescued checkpoint protein expression and reduced DNA damage. We propose miR200-regulated DNA damage checkpoint pathway as a potential therapeutic target for treating complications of diabetes.

  13. 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...

  14. 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.

  15. Studying S-phase DNA Damage Checkpoints using the Fission Yeast Schizosaccharomyces pombe

    Science.gov (United States)

    Willis, Nicholas; Rhind, Nicholas

    2016-01-01

    Slowing of replication in response to DNA damage is a universal response to DNA damage during S-phase. Originally discovered to be defective in checkpoint mutant cells in metazoans, this S-phase DNA damage checkpoint response has been extensively studied in yeast. Unlike other checkpoints that completely arrest cell cycle, the S-phase DNA damage checkpoint slows but does not completely halt replication in response to DNA damage. An analysis of mutants defective in the slowing response requires a sensitive assay to measure this quantitative effect. The use of centrifugal elutriation to synchronize cells and improved techniques in preparing cells for flow cytometry allow for more sensitive and accurate measurement of cells’ ability to slow replication in the presence of DNA damage. This chapter describes the use of transient cdc10-M17 temperature sensitive allele arrest and release combined with centrifugal elutriation to synchronize cells in G1. The S-phase progression of these cells is then assayed by flow cytometry of isolated nuclei, which allows sensitive determination of replication kinetics. PMID:21870281

  16. DISTURBED ANTIGEN PRESENTATION IN CLASSICAL HODGKIN LYMPHOMA; IMPLICATIONS FOR IMMUNE CHECKPOINT INHIBITOR THERAPY?

    NARCIS (Netherlands)

    Nijland, M.; Visser, Lydia; Veenstra, Rianne; Kushekhar, K.; van Imhoff, G.; Berg, van den Anke; Diepstra, A.

    2016-01-01

    Immune checkpoint inhibitors are being tested in clinical trials and show great promise in the treatment of classical Hodgkin lymphoma (cHL). The proposed mechanism of action of these inhibitors consists of reactivating T lymphocytes that have become unresponsive as a consequence of inhibitory mecha

  17. 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...

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

    DEFF Research Database (Denmark)

    Jakobsen, Vibeke; Korpi, Tomas; Lorentzen, Thomas

    with individual level register information allowing us to account for immigrant labour force composition and to examine sub-groups of immigrants. The results indicate that the Danish reforms increased employment among groups of non-Western immigrants while simultaneously decreasing relative earnings. However......Comparing immigrant labour market integration, the OECD ranked the Scandinavian countries Denmark, Norway and Sweden at the bottom. Integration depends on immigration and integration policy, and the countries’ policies have traditionally here been very similar. However, in the early 2000s Denmark...

  19. 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.

  20. Phosphorylation-dependent interactions between Crb2 and Chk1 are essential for DNA damage checkpoint.

    Directory of Open Access Journals (Sweden)

    Meng Qu

    2012-07-01

    Full Text Available In response to DNA damage, the eukaryotic genome surveillance system activates a checkpoint kinase cascade. In the fission yeast Schizosaccharomyces pombe, checkpoint protein Crb2 is essential for DNA damage-induced activation of downstream effector kinase Chk1. The mechanism by which Crb2 mediates Chk1 activation is unknown. Here, we show that Crb2 recruits Chk1 to double-strand breaks (DSBs through a direct physical interaction. A pair of conserved SQ/TQ motifs in Crb2, which are consensus phosphorylation sites of upstream kinase Rad3, is required for Chk1 recruitment and activation. Mutating both of these motifs renders Crb2 defective in activating Chk1. Tethering Crb2 and Chk1 together can rescue the SQ/TQ mutations, suggesting that the main function of these phosphorylation sites is promoting interactions between Crb2 and Chk1. A 19-amino-acid peptide containing these SQ/TQ motifs is sufficient for Chk1 binding in vitro when one of the motifs is phosphorylated. Remarkably, the same peptide, when tethered to DSBs by fusing with either recombination protein Rad22/Rad52 or multi-functional scaffolding protein Rad4/Cut5, can rescue the checkpoint defect of crb2Δ. The Rad22 fusion can even bypass the need for Rad9-Rad1-Hus1 (9-1-1 complex in checkpoint activation. These results suggest that the main role of Crb2 and 9-1-1 in DNA damage checkpoint signaling is recruiting Chk1 to sites of DNA lesions.

  1. The effect of the intra-S-phase checkpoint on origins of replication in human cells.

    Science.gov (United States)

    Karnani, Neerja; Dutta, Anindya

    2011-03-15

    Although many chemotherapy drugs activate the intra-S-phase checkpoint pathway to block S-phase progression, not much is known about how and where the intra-S-phase checkpoint regulates origins of replication in human chromosomes. A genomic analysis of replication in human cells in the presence of hydroxyurea (HU) revealed that only the earliest origins fire, but the forks stall within 2 kb and neighboring clusters of dormant origins are activated. The initiation events are located near expressed genes with a preference for transcription start and end sites, and when they are located in intergenic regions they are located near regulatory factor-binding regions (RFBR). The activation of clustered neo-origins by HU suggests that there are many potential replication initiation sites in permissive parts of the genome, most of which are not used in a normal S phase. Consistent with this redundancy, we see multiple sites bound to MCM3 (representative of the helicase) in the region flanking three out of three origins studied in detail. Bypass of the intra-S-phase checkpoint by caffeine activates many new origins in mid- and late-replicating parts of the genome. The intra-S-phase checkpoint suppresses origin firing after the loading of Mcm10, but before the recruitment of Cdc45 and AND-1/CTF4; i.e., after helicase loading but before helicase activation and polymerase loading. Interestingly, Cdc45 recruitment upon checkpoint bypass was accompanied by the restoration of global Cdk2 kinase activity and decrease in both global and origin-bound histone H3 Lys 4 trimethylation (H3K4me3), consistent with the suggestion that both of these factors are important for Cdc45 recruitment.

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

    Directory of Open Access Journals (Sweden)

    Paula M Checchi

    2011-09-01

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

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

    Science.gov (United States)

    Checchi, Paula M; Engebrecht, JoAnne

    2011-09-01

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

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

    Science.gov (United States)

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

    2016-09-19

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

  5. The Relationship Between Immigrant School Composition, Classmate Support and Involvement in Physical Fighting and Bullying among Adolescent Immigrants and Non-immigrants in 11 Countries.

    Science.gov (United States)

    Walsh, Sophie D; De Clercq, Bart; Molcho, Michal; Harel-Fisch, Yossi; Davison, Colleen M; Madsen, Katrine Rich; Stevens, Gonneke W J M

    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 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 percentage of immigrant adolescents in a school was related to higher levels of physical fighting and bullying perpetration for both immigrant and non-immigrant adolescents and lower levels of victimization for immigrants. In environments of low classmate support, the positive relationship between immigrant school composition and fighting was stronger for non-immigrants than in environments with high classmate support. In environments of low classmate support, the negative relationship between immigrant school composition and fighting and bullying victimization was stronger for immigrant adolescents than in environments with high classmate support. In general, the contribution of immigrant school composition was modest in comparison to the contribution of classmate support. The findings emphasize that it is not just the number of immigrants in a class per se, but rather the environment in the classroom which influences levels of peer violence. The results highlight a need for school intervention programs encouraging positive relations in schools with immigrant populations.

  6. Building the Civic Potential of Immigrant Youth

    Science.gov (United States)

    Obenchain, Kathryn M.; Callahan, Rebecca M.

    2014-01-01

    Social studies emerged at the core of the American common school in the mid-nineteenth century amid the rise of the urban immigrant receiving center. These two forces together resulted in the heightened importance of schools in transforming immigrant students into American citizens. Today, U.S. schools often serve as a social and educational nexus…

  7. 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.

  8. 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…

  9. 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

  10. 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…

  11. 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…

  12. 22 CFR 42.33 - Diversity immigrants.

    Science.gov (United States)

    2010-04-01

    ... NATIONALITY ACT, AS AMENDED Immigrants Subject to Numerical Limitations § 42.33 Diversity immigrants. (a... school education or its equivalent or, within the five years preceding the date of application for a visa..., through publication in the Federal Register and such other methods as will ensure the widest...

  13. LGBT Adult Immigrants in the United States

    OpenAIRE

    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.

  14. 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 assimilat

  15. Immigration and Students' Relationship with Teachers

    Science.gov (United States)

    Peguero, Anthony A.; Bondy, Jennifer M.

    2011-01-01

    Students' relationship with teachers is a building block toward student progress and success. Little is known, however, about the relationships the children of immigrants have with their teachers, which is particularly relevant today in the midst of the current social, political, and economic debate over the influence of immigration in U.S.…

  16. 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......, we find that those with the poorest labour market prospects are the least responsive to the improvement in economic incentiv...

  17. Second-Language Literacy, Immigration, and Globalization

    Science.gov (United States)

    Soto Huerta, M. E.; Pérez, B.

    2015-01-01

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

  18. Adult Education, Migration and Immigrant Education.

    Science.gov (United States)

    de Cossio, Roger Diaz

    Mexico is experiencing major reform in adult education. At the same time, Mexico has been the largest producer of immigrants into the United States in the last 50 years. At the beginning of the century, non-English-speaking immigrants were only required to learn enough English to perform their jobs. As the Mexican-American community grew, it…

  19. 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.

  20. Illegal Immigrants in Canada: Recent Developments.

    Science.gov (United States)

    Robinson, W. G.

    1984-01-01

    Naturally protected by its distance from most migrant routes and with a long undefended border with the U.S., a parliamentary system capable of responding rapidly to problems, and a small legal and even smaller illegal immigrant population, Canada has experimented with novel immigration policies to encourage and control its population increase.…

  1. 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…

  2. 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)

  3. Requiring human papillomavirus vaccine for immigrant women.

    Science.gov (United States)

    Hachey, Krista J; Allen, Rebecca H; Nothnagle, Melissa; Boardman, Lori A

    2009-11-01

    The Centers for Disease Control and Prevention Advisory Committee on Immunization Practices recommends human papillomavirus (HPV) vaccination of 11- to 12-year-old girls, with catch-up vaccination for girls and women aged 13 to 26 years. Although compulsory HPV vaccination is not currently mandated for any U.S. population, immigrant women aged 11-26 years are now required to receive the first injection of the vaccine (the full series consists of three doses) as a result of the 1996 Illegal Immigration Reform and Immigrant Responsibility Act. According to this law, immigrants applying for visas to enter the United States or to adjust their immigration status must receive the inoculations that the Advisory Committee on Immunization Practices recommends for U.S. residents. In the case of HPV, this law represents not only an undue burden on immigrant women, but also raises scientific and ethical questions regarding the benefit of vaccination in this population. Given these issues, immigrant women should not be required to provide documentation of HPV vaccination at the time of visa application or adjustment of immigration status.

  4. Recent immigration and studies of ethnic assimilation.

    Science.gov (United States)

    Taeuber, A F; Taeuber, K E

    1967-06-01

    Studies of ethnic assimilation are frequently based upon status comparisons between the foreign born and their "children," the second generation. The assumption that recent immigration has been negligible and that the foreign born represent a closed population is implicit in that procedure. However, analysis of official statistics indicates that immigrants who arrived since World War II now comprise a substantial share of the foreign-born population, while the foreign born who arrived before quota restrictions are rapidly being depleted by mortality. Recent immigrants, as intended by quota legislation, are of much higher socioeconomic status than immigrants who arrived before World War 1. Hence, characteristics of both recent immigrants and earlier arrivals are confounded in data for the foreign-born population. Existing data do not permit rigorous assessment of this confusion or adequate control for it. This paper suggests that tabulations of the foreign born by "year of arrival" would improve the sociological utility of data for ethnic groups.

  5. The healthy immigrant effect and mortality rates.

    Science.gov (United States)

    Ng, Edward

    2011-12-01

    According to the 2006 Census, almost the Canadian population were foreign-born, a percentage that is projected to reach at least 25% by 2031. Studies based on age-standardized mortality rates (ASMR) have found a healthy immigrant effect, with lower overall rates among immigrants. A duration effect has also been observed-immigrants' mortality advantage lessened as their time in Canada increased. ASMRs based on the 1991 to 2001 census mortality follow-up study indicate a healthy immigrant effect and a duration effect at the national level for all-cause mortality for both sexes. However, at the national level, the mortality rate among women from the United States and from Sub-Saharan Africa was similar to that of Canadian-born women. For the three largest Census Metropolitan Areas (Toronto, Montreal and Vancouver), a healthy immigrant effect was not observed among women or among most men from the United States or Sub-Saharan Africa.

  6. [Depressive syndromes in the immigrant population].

    Science.gov (United States)

    Ochoa Mangado, E; Vicente Muelas, N; Lozano Suárez, M

    2005-03-01

    Migrations are currently one of the most important sociocultural and political phenomena. As a rule, immigrants are in good health, although the immigration is by itself a mental health risk factor. This population shows common specific problems as adaptation processes, depressive syndromes, or other psychiatric problems. "Ulises' syndrome", depression, and dysthymia are the most common mental health conditions among unlawful non-european community immigrants cared in specific facilities. Similarly to the spanish indigenous population, anxiety disorders and readjustment disorders are the most common diagnoses among legal immigrants cared by Mental Health Services (MHS). Given the impact of sociocultural aspects in the development and clinical manifestations of mental health problems, it is necessary to know the demands of the immigrant population and to adjust current facilities for their care.

  7. All about U.S. immigration statistics.

    Science.gov (United States)

    Hoefer, M

    1989-01-01

    The quality of data collected by the U.S. Immigration and Naturalization Service (INS) is assessed, with a focus on differences between U.S. and U.N. definitions of immigrants, emigrants, and refugees. The author suggests that "gaps in migration data collected for the U.S. limit their usefulness for studying international migration and estimating national population change. For example, no information is collected on emigration of legal permanent residents or U.S. citizens, nor is there any direct information on the immigration of U.S. citizens. Data collected on legal immigrants are based on a legal and administrative definition that often conflicts with the demographic definition of an immigrant."

  8. 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.

  9. Do immigrants work in riskier jobs?

    Science.gov (United States)

    Orrenius, Pia M; Zavodny, Madeline

    2009-08-01

    Recent media and government reports suggest that immigrants are more likely to hold jobs with poor working conditions than U.S.-born workers, perhaps because immigrants work in jobs that "natives don't want." Despite this widespread view, earlier studies have not found immigrants to be in riskier jobs than natives. This study combines individual-level data from the 2003-2005 American Community Survey with Bureau of Labor Statistics data on work-related injuries and fatalities to take afresh look at whether foreign-born workers are employed in more dangerous jobs. The results indicate that immigrants are in fact more likely to work in risky jobs than U.S.-born workers, partly due to differences in average characteristics, such as immigrants' lower English-language ability and educational attainment.

  10. Language Barriers and Immigrant Health.

    Science.gov (United States)

    Clarke, Andrew; Isphording, Ingo E

    2016-05-24

    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.

  11. A mitotic phosphorylation feedback network connects Cdk1, Plk1, 53BP1, and Chk2 to inactivate the G(2)/M DNA damage checkpoint

    DEFF Research Database (Denmark)

    van Vugt, Marcel A T M; Gardino, Alexandra K; Linding, Rune;

    2010-01-01

    the DNA damage response. We demonstrate that the non-enzymatic checkpoint adaptor protein 53BP1 is an in vivo target of the cell cycle kinases Cyclin-dependent kinase-1 and Polo-like kinase-1 (Plk1). We show that Plk1 binds 53BP1 during mitosis and that this interaction is required for proper inactivation......DNA damage checkpoints arrest cell cycle progression to facilitate DNA repair. The ability to survive genotoxic insults depends not only on the initiation of cell cycle checkpoints but also on checkpoint maintenance. While activation of DNA damage checkpoints has been studied extensively, molecular...... of the DNA damage checkpoint. 53BP1 mutants that are unable to bind Plk1 fail to restart the cell cycle after ionizing radiation-mediated cell cycle arrest. Importantly, we show that Plk1 also phosphorylates the 53BP1-binding checkpoint kinase Chk2 to inactivate its FHA domain and inhibit its kinase activity...

  12. The internal Cdc20 binding site in BubR1 facilitates both spindle assembly checkpoint signalling and silencing

    DEFF Research Database (Denmark)

    Lischetti, Tiziana; Zhang, Gang; Sedgwick, Garry G;

    2014-01-01

    Improperly attached kinetochores activate the spindle assembly checkpoint (SAC) and by an unknown mechanism catalyse the binding of two checkpoint proteins, Mad2 and BubR1, to Cdc20 forming the mitotic checkpoint complex (MCC). Here, to address the functional role of Cdc20 kinetochore localization...... on the SAC because the IC20BD is also required for efficient SAC silencing. Indeed, the IC20BD can disrupt the MCC providing a mechanism for its role in SAC silencing. We thus uncover an unexpected dual function of the second Cdc20 binding site in BubR1 in promoting both efficient SAC signalling and SAC...

  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 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...

  15. 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...

  16. 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...

  17. 8 CFR 1235.6 - Referral to immigration judge.

    Science.gov (United States)

    2010-01-01

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

  18. 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…

  19. Making It in America: Social Mobility in the Immigrant Population

    Science.gov (United States)

    Borjas, George J.

    2006-01-01

    In his survey of research on social mobility and U.S. immigration, George Borjas underscores two insights. First, most immigrants are at a sizable earnings disadvantage, relative to nativeborn workers. Second, the earnings of different groups of immigrants vary widely. The children of immigrants "catch up" to native-born workers slowly.…

  20. Heaven's Door: Immigration Policy and the American Economy.

    Science.gov (United States)

    Borjas, George J.

    This book discusses the economics of immigration, analyzing immigrants' skills, national origins, welfare use, economic mobility, and impact on the labor market and using new data to trace current trends in ethnic segregation. Twelve chapters examine (1) "Reframing the Immigration Debate"; (2) "The Skills of Immigrants"; (3)…

  1. Culturally Responsive Leadership: Best Practice in Integrating Immigrant Students

    Science.gov (United States)

    Magno, Cathyrn; Schiff, Margo

    2010-01-01

    Immigration to the US has fluctuated with economic conditions and with American immigration policies. Historically, most immigrants settled in urban areas, while suburban towns and their schools remained almost completely homogeneous and overwhelmingly White. Today, roughly one in five children in the US comes from an immigrant home, altering the…

  2. 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

  3. Addressing Illegal Immigrants Inside the United States: A Policy Analysis

    Science.gov (United States)

    2007-03-01

    20 Ibid., 1–44. 21 Roberto Suro , “Attitudes toward Immigrants and Immigration Policy: Surveys among Latinos in the U.S. and in Mexico,” Pew...February 16, 2007. Suro , Roberto. “Attitudes toward Immigrants and Immigration Policy: Surveys among Latinos in the U.S. and in Mexico.” Pew Hispanic

  4. 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…

  5. Framing unauthorized immigrants: the effects of labels on evaluations.

    Science.gov (United States)

    Ommundsen, Reidar; Van der Veer, Kees; Larsen, Knud S; Eilertsen, Dag-Erik

    2014-04-01

    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 are not well documented. In this replication study, 274 undergraduate students in psychology responded to one of three randomly distributed versions of a 20-item scale measuring attitudes toward unauthorized immigration. The items in the three scale versions varyingly referred to immigrants using the three terms. Results showed differences in attitudes toward unauthorized immigration between all experimental conditions. The label "illegal immigrants" yielded significantly less positive attitudes compared to the label "undocumented immigrants," and respondents exposed to the label "illegal aliens" showed the most positive attitudes. Furthermore, the effects of the experimental conditions were not moderated by the respondents' patriotism, sex, or own immigrant background.

  6. Achievement and Expectations of Immigrant, Second Generation, and Non-Immigrant Black Students in U.S. Higher Education

    Science.gov (United States)

    Hudley, Cynthia

    2016-01-01

    Research on academic achievement contrasting Black immigrant, second generation, and non-immigrant students as distinct groups is surprisingly sparse in the higher education literature. This study examined Black immigrant and second generation undergraduates from Africa and the Caribbean and non-immigrant Black American undergraduates, using the…

  7. [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)

  8. Empirical characteristics of legal and illegal immigrants in the US

    OpenAIRE

    Caponi, Vincenzo; Plesca, Miana

    2013-01-01

    We combine the New Immigrant Survey (NIS), which contains information on US legal immigrants, with the American Community Survey (ACS), which contains information on legal and illegal immigrants to the U.S. Using econometric methodology proposed by Lancaster and Imbens (1996) we compute the probability for each observation in the ACS data to refer to an illegal immigrant, conditional on observed characteristics. The results for illegal versus legal immigrants are novel, since no other work ha...

  9. Policies of inclusion: immigrants, disease, dependency, and American immigration policy at the dawn and dusk of the 20th century.

    Science.gov (United States)

    Fairchild, Amy L

    2004-04-01

    The racial politics of immigration have punctuated national discussions about immigration at different periods in US history, particularly when concerns about losing an American way of life or American population have coincided with concerns about infectious diseases. Nevertheless, the main theme running through American immigration policy is one of inclusion. The United States has historically been a nation reliant on immigrant labor and, accordingly, the most consequential public policies regarding immigration have responded to disease and its economic burdens by seeking to control the behavior of immigrants within our borders rather than excluding immigrants at our borders.

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

    OpenAIRE

    Checchi, Paula M.; JoAnne Engebrecht

    2011-01-01

    Meiosis is a specialized form of cellular division that results in the precise halving of the genome to produce gametes for sexual reproduction. Checkpoints function during meiosis to detect errors and subsequently to activate a signaling cascade that prevents the formation of aneuploid gametes. Indeed, asynapsis of a homologous chromosome pair elicits a checkpoint response that can in turn trigger germline apoptosis. In a heterogametic germ line, however, sex chromosomes proceed through meio...

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

    OpenAIRE

    Mihailo Mirkovic; Lukas H. Hutter; Béla Novák; Raquel A. Oliveira

    2015-01-01

    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 r...

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

    OpenAIRE

    Mirkovic, Mihailo; Hutter, Lukas H.; Novák, Béla; Oliveira, Raquel A.

    2015-01-01

    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 r...

  13. 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.

  14. Poverty and program participation among immigrant children.

    Science.gov (United States)

    Borjas, George J

    2011-01-01

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

  15. Limit theorems for fragmentation processes with immigration

    CERN Document Server

    Knobloch, Robert

    2012-01-01

    In this paper we extend two limit theorems which were recently obtained for fragmentation processes to such processes with immigration. More precisely, in the setting with immigration we consider a limit theorem for the process counted with a random characteristic as well as the asymptotic behaviour of an empirical measure associated with the stopping line corresponding to the first blocks, in their respective line of descent, that are smaller than a given size. In addition, we determine the asymptotic decay rate of the size of the largest block in a homogeneous fragmentation process with immigration. The techniques used to proves these results are based on submartingale arguments.

  16. 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."

  17. Integration and immigration pressures in western Europe.

    Science.gov (United States)

    Bohning, W R

    1991-01-01

    "With xenophobia resurgent in Europe, this article addresses some of the complexities of immigration and integration in EC [European Community] and EFTA [European Free Trade Association] countries. The categories of legal and illegal immigrants (including estimates thereof) are first described, as are the necessary ingredients of an integration policy (a framework law, a secure environment, cultural tolerance, demarginalization in housing and the labour market). The author then considers what types of action would help to ease the present immigration pressure, discussing in turn quota policies, project-tied or training migration and, finally, the use of international aid."

  18. 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.

  19. Determinants of Recent Immigrants' Location Choices

    DEFF Research Database (Denmark)

    Damm, Anna Piil

    2009-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  1. Overview and management of toxicities of immune checkpoint-blocking drugs

    Directory of Open Access Journals (Sweden)

    Economopoulou Panagiota

    2016-03-01

    Full Text Available Immunotherapy is considered to be the most important breakthrough in cancer management in the past few years. This success was based on the scientific understanding of immune mechanisms due to improvement in preclinical science and the introduction of new methods of investigation. Immune checkpoint inhibitors (ICIs are among the most promising drugs in the field of immune-oncology; they represent monoclonal antibodies that modulate the effects of immune checkpoints, such as cytotoxic T lymphocyte Antigen 4 (CTLA-4 and Programmed Cell Death protein 1 (PD-1, which are co-inhibitory signals responsible for immune suppression. Despite clinical benefits, ICIs are immune activating agents that are associated with a number of important side effects (immune-related adverse events-irAEs, attributed to organ-specific inflammation. Herein, we review the toxicities of ICIs, highlighting the importance of early identification and management.

  2. Negative immune checkpoints on T lymphocytes and their relevance to cancer immunotherapy.

    Science.gov (United States)

    Śledzińska, Anna; Menger, Laurie; Bergerhoff, Katharina; Peggs, Karl S; Quezada, Sergio A

    2015-12-01

    The term 'inhibitory checkpoint' refers to the broad spectrum of co-receptors expressed by T cells that negatively regulate T cell activation thus playing a crucial role in maintaining peripheral self-tolerance. Co-inhibitory receptor ligands are highly expressed by a variety of malignancies allowing evasion of anti-tumour immunity. Recent studies demonstrate that manipulation of these co-inhibitory pathways can remove the immunological brakes that impede endogenous immune responses against tumours. Antibodies that block the interactions between co-inhibitory receptors and their ligands have delivered very promising clinical responses, as has been shown by recent successful trials targeting the CTLA-4 and PD-1 pathways. In this review, we discuss the mechanisms of action and expression pattern of co-inhibitory receptors on different T cells subsets, emphasising differences between CD4(+) and CD8(+) T cells. We also summarise recent clinical findings utilising immune checkpoint blockade.

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

    Directory of Open Access Journals (Sweden)

    Gloria Mittica

    2016-07-01

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

  4. Social and ethical checkpoints for bottom-up synthetic biology, or protocells.

    Science.gov (United States)

    Bedau, Mark A; Parke, Emily C; Tangen, Uwe; Hantsche-Tangen, Brigitte

    2009-12-01

    An alternative to creating novel organisms through the traditional "top-down" approach to synthetic biology involves creating them from the "bottom up" by assembling them from non-living components; the products of this approach are called "protocells." In this paper we describe how bottom-up and top-down synthetic biology differ, review the current state of protocell research and development, and examine the unique ethical, social, and regulatory issues raised by bottom-up synthetic biology. Protocells have not yet been developed, but many expect this to happen within the next five to ten years. Accordingly, we identify six key checkpoints in protocell development at which particular attention should be given to specific ethical, social and regulatory issues concerning bottom-up synthetic biology, and make ten recommendations for responsible protocell science that are tied to the achievement of these checkpoints.

  5. Intestinal microbiome analyses identify melanoma patients at risk for checkpoint-blockade-induced colitis.

    Science.gov (United States)

    Dubin, Krista; Callahan, Margaret K; Ren, Boyu; Khanin, Raya; Viale, Agnes; Ling, Lilan; No, Daniel; Gobourne, Asia; Littmann, Eric; Huttenhower, Curtis; Pamer, Eric G; Wolchok, Jedd D

    2016-02-02

    The composition of the intestinal microbiota influences the development of inflammatory disorders. However, associating inflammatory diseases with specific microbial members of the microbiota is challenging, because clinically detectable inflammation and its treatment can alter the microbiota's composition. Immunologic checkpoint blockade with ipilimumab, a monoclonal antibody that blocks cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) signalling, is associated with new-onset, immune-mediated colitis. Here we conduct a prospective study of patients with metastatic melanoma undergoing ipilimumab treatment and correlate the pre-inflammation faecal microbiota and microbiome composition with subsequent colitis development. We demonstrate that increased representation of bacteria belonging to the Bacteroidetes phylum is correlated with resistance to the development of checkpoint-blockade-induced colitis. Furthermore, a paucity of genetic pathways involved in polyamine transport and B vitamin biosynthesis is associated with an increased risk of colitis. Identification of these biomarkers may enable interventions to reduce the risk of inflammatory complications following cancer immunotherapy.

  6. An Overview of the Spindle Assembly Checkpoint Status in Oral Cancer

    Directory of Open Access Journals (Sweden)

    José Henrique Teixeira

    2014-01-01

    Full Text Available Abnormal chromosome number, or aneuploidy, is a common feature of human solid tumors, including oral cancer. Deregulated spindle assembly checkpoint (SAC is thought as one of the mechanisms that drive aneuploidy. In normal cells, SAC prevents anaphase onset until all chromosomes are correctly aligned at the metaphase plate thereby ensuring genomic stability. Significantly, the activity of this checkpoint is compromised in many cancers. While mutations are rather rare, many tumors show altered expression levels of SAC components. Genomic alterations such as aneuploidy indicate a high risk of oral cancer and cancer-related mortality, and the molecular basis of these alterations is largely unknown. Yet, our knowledge on the status of SAC components in oral cancer remains sparse. In this review, we address the state of our knowledge regarding the SAC defects and the underlying molecular mechanisms in oral cancer, and discuss their therapeutic relevance, focusing our analysis on the core components of SAC and its target Cdc20.

  7. Targeting KIT on innate immune cells to enhance the antitumor activity of checkpoint inhibitors.

    Science.gov (United States)

    Stahl, Maximilian; Gedrich, Richard; Peck, Ronald; LaVallee, Theresa; Eder, Joseph Paul

    2016-06-01

    Innate immune cells such as mast cells and myeloid-derived suppressor cells are key components of the tumor microenvironment. Recent evidence indicates that levels of myeloid-derived suppressor cells in melanoma patients are associated with poor survival to checkpoint inhibitors. This suggests that targeting both the innate and adaptive suppressive components of the immune system will maximize clinical benefit and elicit more durable responses in cancer patients. Preclinical data suggest that targeting signaling by the receptor tyrosine kinase KIT, particularly on mast cells, may modulate innate immune cell numbers and activity in tumors. Here, we review data highlighting the importance of the KIT signaling in regulating antitumor immune responses and the potential benefit of combining selective KIT inhibitors with immune checkpoint inhibitors.

  8. The chromosomal passenger complex and the spindle assembly checkpoint: kinetochore-microtubule error correction and beyond

    OpenAIRE

    Maia André F; Vader Gerben; Lens Susanne MA

    2008-01-01

    Abstract During mitosis, correct bipolar chromosome attachment to the mitotic spindle is an essential prerequisite for the equal segregation of chromosomes. The spindle assembly checkpoint can prevent chromosome segregation as long as not all chromosome pairs have obtained bipolar attachment to the spindle. The chromosomal passenger complex plays a crucial role during chromosome alignment by correcting faulty chromosome-spindle interactions (e.g. attachments that do not generate tension). In ...

  9. Glioblastoma Eradication Following Immune Checkpoint Blockade in an Orthotopic, Immunocompetent Model.

    Science.gov (United States)

    Reardon, David A; Gokhale, Prafulla C; Klein, Sarah R; Ligon, Keith L; Rodig, Scott J; Ramkissoon, Shakti H; Jones, Kristen L; Conway, Amy Saur; Liao, Xiaoyun; Zhou, Jun; Wen, Patrick Y; Van Den Abbeele, Annick D; Hodi, F Stephen; Qin, Lei; Kohl, Nancy E; Sharpe, Arlene H; Dranoff, Glenn; Freeman, Gordon J

    2016-02-01

    Inhibition of immune checkpoints, including cytotoxic T-lymphocyte antigen-4 (CTLA-4), programmed death-1 (PD-1), and its ligand PD-L1, has demonstrated exciting and durable remissions across a spectrum of malignancies. Combinatorial regimens blocking complementary immune checkpoints further enhance the therapeutic benefit. The activity of these agents for patients with glioblastoma, a generally lethal primary brain tumor associated with significant systemic and microenvironmental immunosuppression, is not known. We therefore systematically evaluated the antitumor efficacy of murine antibodies targeting a broad panel of immune checkpoint molecules, including CTLA-4, PD-1, PD-L1, and PD-L2 when administered as single-agent therapy and in combinatorial regimens against an orthotopic, immunocompetent murine glioblastoma model. In these experiments, we observed long-term tumor-free survival following single-agent anti-PD-1, anti-PD-L1, or anti-CTLA-4 therapy in 50%, 20%, and 15% of treated animals, respectively. Combination therapy of anti-CTLA-4 plus anti-PD-1 cured 75% of the animals, even against advanced, later-stage tumors. In long-term survivors, tumor growth was not seen upon intracranial tumor rechallenge, suggesting that tumor-specific immune memory responses were generated. Inhibitory immune checkpoint blockade quantitatively increased activated CD8(+) and natural killer cells and decreased suppressive immune cells in the tumor microenvironment and draining cervical lymph nodes. Our results support prioritizing the clinical evaluation of PD-1, PD-L1, and CTLA-4 single-agent targeted therapy as well as combination therapy of CTLA-4 plus PD-1 blockade for patients with glioblastoma.

  10. Handoff Based Secure Checkpointing and Log Based Rollback Recovery for Mobile Hosts

    Directory of Open Access Journals (Sweden)

    Priyanka Dey and Suparna Biswas

    2012-10-01

    Full Text Available An efficient fault tolerant algorithm based on movement-based secure checkpointing and logging formobile computing system is proposed here. The recovery scheme proposed here combines independentcheckpointing and message logging. Here we consider mobility rate of the user in checkpointing so thatmobile host can manage recovery information such as checkpoints and logs properly so that a mobilehost takes less recovery time after failure. Mobile hosts save checkpoints when number of hand-offexceeds a predefined hand-off threshold value. Current approaches save logs in base station. But thisapproach maximizes recovery time if message passing frequency is large. If a mobile host saves log in itsown memory, recovery cost will be less because log retrieval time will be small after failure. But there isa probability of memory crash of a mobile host. In that case logs can not be retrieved if it is saved only inmobile node. If the failure is transient then logs can be retrieved from the memory of mobile node.Hence in this algorithm mobile hosts also save log in own memory and base station. In case of crashrecovery, log will be retrieved from base station and in case of transient failure recovery logs will beretrieved from mobile host. In this algorithm recovery probability is optimized and total recovery time isreduced in comparison to existing works. Logs are very small in size. Hence saving logs in mobile hostsdoes not cause much memory overhead. Hand-off threshold is a function of mobility rate, messagepassing frequency and failure rate of mobile hosts. This algorithm describes a secure check pointingtechnique as a method for providing fault tolerance while preventing information leakage through thecheckpoint data.

  11. Differential activation of intra-S-phase checkpoint in response to tripchlorolide and its effects on DNA replication

    Institute of Scientific and Technical Information of China (English)

    Yan REN; Jia Rui WU

    2004-01-01

    DNA replication is tightly regulated during the S phase of the cell cycle, and the activation of the intra-S-phase checkpoint due to DNA damage usually results in arrest of DNA synthesis. However, the molecular details about the correlation between the checkpoint and regulation of DNA replication are still unclear. To investigate the connections between DNA replication and DNA damage checkpoint, a DNA-damage reagent, tripchlorolide, was applied to CHO (Chinese ovary hamster) cells at early- or middle-stages of the S phase. The early-S-phase treatment with TC significantly delayed the progression of the S phase and caused the phosphorylation of the Chk1 checkpoint protein, whereas the middle-S-phase treatment only slightly slowed down the progression of the S phase. Furthermore, the analysis of DNA replication patterns revealed that replication pattern Ⅱ was greatly prolonged in the cells treated with the drug during the early-S phase, whereas the late-replication patterns of these cells were hardly detected, suggesting that the activation of the intra-S-phase checkpoint inhibits the late-origin firing of DNA replication. We conclude that cells at different stages of the S phase are differentially sensitive to the DNA-damage reagent, and the activation of the intra-Sphase checkpoint blocks the DNA replication progression in the late stage of S phase.

  12. 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.

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

    Science.gov (United States)

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

    2016-05-01

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

  14. DTL/CDT2 is essential for both CDT1 regulation and the early G2/M checkpoint.

    Science.gov (United States)

    Sansam, Christopher L; Shepard, Jennifer L; Lai, Kevin; Ianari, Alessandra; Danielian, Paul S; Amsterdam, Adam; Hopkins, Nancy; Lees, Jacqueline A

    2006-11-15

    Checkpoint genes maintain genomic stability by arresting cells after DNA damage. Many of these genes also control cell cycle events in unperturbed cells. By conducting a screen for checkpoint genes in zebrafish, we found that dtl/cdt2 is an essential component of the early, radiation-induced G2/M checkpoint. We subsequently found that dtl/cdt2 is required for normal cell cycle control, primarily to prevent rereplication. Both the checkpoint and replication roles are conserved in human DTL. Our data indicate that the rereplication reflects a requirement for DTL in regulating CDT1, a protein required for prereplication complex formation. CDT1 is degraded in S phase to prevent rereplication, and following DNA damage to prevent origin firing. We show that DTL associates with the CUL4-DDB1 E3 ubiquitin ligase and is required for CDT1 down-regulation in unperturbed cells and following DNA damage. The cell cycle defects of Dtl-deficient zebrafish are suppressed by reducing Cdt1 levels. In contrast, the early G2/M checkpoint defect appears to be Cdt1-independent. Thus, DTL promotes genomic stability through two distinct mechanisms. First, it is an essential component of the CUL4-DDB1 complex that controls CDT1 levels, thereby preventing rereplication. Second, it is required for the early G2/M checkpoint.

  15. 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.

  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. p53 activates G₁ checkpoint following DNA damage by doxorubicin during transient mitotic arrest.

    Science.gov (United States)

    Hyun, Sun-Yi; Jang, Young-Joo

    2015-03-10

    Recovery from DNA damage is critical for cell survival. The serious damage is not able to be repaired during checkpoint and finally induces cell death to prevent abnormal cell growth. In this study, we demonstrated that 8N-DNA contents are accumulated via re-replication during prolonged recovery period containing serious DNA damage in mitotic cells. During the incubation for recovery, a mitotic delay and initiation of an abnormal interphase without cytokinesis were detected. Whereas a failure of cytokinesis occurred in cells with no relation with p53/p21, re-replication is an anomalous phenomenon in the mitotic DNA damage response in p53/p21 negative cells. Cells with wild-type p53 are accumulated just prior to the initiation of DNA replication through a G₁ checkpoint after mitotic DNA damage, even though p53 does not interrupt pre-RC assembly. Finally, these cells undergo cell death by apoptosis. These data suggest that p53 activates G₁ checkpoint in response to mitotic DNA damage. Without p53, cells with mitotic DNA damage undergo re-replication leading to accumulation of damage.

  18. Dovitinib induces mitotic defects and activates the G2 DNA damage checkpoint.

    Science.gov (United States)

    Man, Wing Yu; Mak, Joyce P Y; Poon, Randy Y C

    2014-01-01

    Dovitinib (TKI258; formerly CHIR-258) is an orally bioavailable inhibitor of multiple receptor tyrosine kinases. Interestingly, Dovitinib triggered a G2 /M arrest in cancer cell lines from diverse origins including HeLa, nasopharyngeal carcinoma, and hepatocellular carcinoma. Single-cell analysis revealed that Dovitinib promoted a delay in mitotic exit in a subset of cells, causing the cells to undergo mitotic slippage. Higher concentrations of Dovitinib induced a G2 arrest similar to the G2 DNA damage checkpoint. In support of this, DNA damage was triggered by Dovitinib as revealed by γ-H2AX and comet assays. The mitotic kinase CDK1 was found to be inactivated by phosphorylation in the presence of Dovitinib. Furthermore, the G2 arrest could be overcome by abrogation of the G2 DNA damage checkpoint using small molecule inhibitors of CHK1 and WEE1. Finally, Dovitinib-mediated G2 cell cycle arrest and subsequent cell death could be promoted after DNA damage repair was disrupted by inhibitors of poly(ADP-ribose) polymerases. These results are consistent with the recent finding that Dovitinib can also target topoisomerases. Collectively, these results suggest additional directions for use of Dovitinib, in particular with agents that target the DNA damage checkpoint.

  19. WEE1 inhibition targets cell cycle checkpoints for triple negative breast cancers to overcome cisplatin resistance

    Science.gov (United States)

    Zheng, Hongping; Shao, Fangyuan; Martin, Scots; Xu, Xiaoling; Deng, Chu-Xia

    2017-01-01

    Cisplatin is one of the most commonly used therapeutic drugs for cancer therapy, yet prolonged cisplatin treatment frequently results in drug resistance. To enhance therapeutic effect of cisplatin, we conducted a high throughput screening using a kinase library containing 704 kinases against triple negative breast cancer (TNBC) cells. We demonstrated that cisplatin activates ATR, CHK1 and WEE1, which shut down DNA replication and attenuate cisplatin induced-lethality. WEE1 inhibition sensitizes TNBCs and cisplatin resistant cancer cells to cisplatin-induced lethality, because it not only impairs DNA replication checkpoint more profoundly than inhibition of ATR or CHK1, but also defects G2-M cell cycle checkpoint. Finally, we demonstrated that combined cisplatin treatment and WEE1 inhibition synergistically inhibits xenograft cancer growth accompanied by markedly reduced expression of TNBC signature genes. Thus targeting DNA replication and G2-M cell cycle checkpoint simultaneously by cisplatin and WEE1 inhibition is promising for TNBCs treatment, and for overcoming their cisplatin resistance. PMID:28262781

  20. Adaptive resistance to therapeutic PD-1 blockade is associated with upregulation of alternative immune checkpoints

    Science.gov (United States)

    Koyama, Shohei; Akbay, Esra A.; Li, Yvonne Y.; Herter-Sprie, Grit S.; Buczkowski, Kevin A.; Richards, William G.; Gandhi, Leena; Redig, Amanda J.; Rodig, Scott J.; Asahina, Hajime; Jones, Robert E.; Kulkarni, Meghana M.; Kuraguchi, Mari; Palakurthi, Sangeetha; Fecci, Peter E.; Johnson, Bruce E.; Janne, Pasi A.; Engelman, Jeffrey A.; Gangadharan, Sidharta P.; Costa, Daniel B.; Freeman, Gordon J.; Bueno, Raphael; Hodi, F. Stephen; Dranoff, Glenn; Wong, Kwok-Kin; Hammerman, Peter S.

    2016-01-01

    Despite compelling antitumour activity of antibodies targeting the programmed death 1 (PD-1): programmed death ligand 1 (PD-L1) immune checkpoint in lung cancer, resistance to these therapies has increasingly been observed. In this study, to elucidate mechanisms of adaptive resistance, we analyse the tumour immune microenvironment in the context of anti-PD-1 therapy in two fully immunocompetent mouse models of lung adenocarcinoma. In tumours progressing following response to anti-PD-1 therapy, we observe upregulation of alternative immune checkpoints, notably T-cell immunoglobulin mucin-3 (TIM-3), in PD-1 antibody bound T cells and demonstrate a survival advantage with addition of a TIM-3 blocking antibody following failure of PD-1 blockade. Two patients who developed adaptive resistance to anti-PD-1 treatment also show a similar TIM-3 upregulation in blocking antibody-bound T cells at treatment failure. These data suggest that upregulation of TIM-3 and other immune checkpoints may be targetable biomarkers associated with adaptive resistance to PD-1 blockade. PMID:26883990

  1. Immunologic checkpoints in cancer therapy: focus on the programmed death-1 (PD-1 receptor pathway

    Directory of Open Access Journals (Sweden)

    Momtaz P

    2014-11-01

    Full Text Available Parisa Momtaz,1,2 Michael A Postow1,2 1Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA; 2Weill Cornell Medical College, New York, NY, USA Abstract: T-lymphocytes have the potential to recognize cancer antigens as foreign and therefore eliminate them. However, immune checkpoints such as cytotoxic T-lymphocyte-associated antigen (CTLA-4 and programmed cell death (PD-1 receptor and its ligands (PD-L1, PD-L2 suppress the activity of T-lymphocytes. Advances in the understanding of immunology and its role in cancer have led to the development of immune checkpoint inhibitors that block CTLA-4 and PD-1 and result in durable responses in patients with a wide range of cancers. PD-1 and PD-L1 inhibitors are currently in many stages of clinical investigation, and the anti-PD-1 antibody, pembrolizumab, was recently approved by the US Food and Drug Administration. Many questions remain to be answered, such as the optimal administration schedule, biomarkers that associate with benefit, and potential for use of PD-1 agents in combination approaches. Nonetheless, immunotherapy with PD-1 blocking antibodies is now becoming an integral part in the management of cancer. Keyword: immune checkpoints, immunotherapy, programmed cell death protein-1, cytotoxic T-lymphocyte antigen 4

  2. 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

  3. WEE1 inhibition targets cell cycle checkpoints for triple negative breast cancers to overcome cisplatin resistance.

    Science.gov (United States)

    Zheng, Hongping; Shao, Fangyuan; Martin, Scots; Xu, Xiaoling; Deng, Chu-Xia

    2017-03-06

    Cisplatin is one of the most commonly used therapeutic drugs for cancer therapy, yet prolonged cisplatin treatment frequently results in drug resistance. To enhance therapeutic effect of cisplatin, we conducted a high throughput screening using a kinase library containing 704 kinases against triple negative breast cancer (TNBC) cells. We demonstrated that cisplatin activates ATR, CHK1 and WEE1, which shut down DNA replication and attenuate cisplatin induced-lethality. WEE1 inhibition sensitizes TNBCs and cisplatin resistant cancer cells to cisplatin-induced lethality, because it not only impairs DNA replication checkpoint more profoundly than inhibition of ATR or CHK1, but also defects G2-M cell cycle checkpoint. Finally, we demonstrated that combined cisplatin treatment and WEE1 inhibition synergistically inhibits xenograft cancer growth accompanied by markedly reduced expression of TNBC signature genes. Thus targeting DNA replication and G2-M cell cycle checkpoint simultaneously by cisplatin and WEE1 inhibition is promising for TNBCs treatment, and for overcoming their cisplatin resistance.

  4. 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...

  5. Association between Integration Policies and Immigrants' Mortality

    DEFF Research Database (Denmark)

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

    2015-01-01

    confounders and data comparability issues (e.g., French cross-sectional data) may affect the findings, this study suggests that different macro-level policy contexts may influence immigrants' mortality. Comparable mortality registration systems across Europe along with detailed socio-demographic information......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...... rated integration policies. OBJECTIVE: To analyse mortality differences of immigrants from the same country of origin living in countries with distinct integration policy contexts. METHODS: From the mortality dataset collected in the Migrant Ethnic Health Observatory (MEHO) project, we chose...

  6. David Miller on Immigration Policy and Nationality

    DEFF Research Database (Denmark)

    Lægaard, Sune

    2007-01-01

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

  7. 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...

  8. Emerging Issues in Migration, Emigration, and Immigration.

    Science.gov (United States)

    Journal of Intergroup Relations, 1984

    1984-01-01

    Reports on findings presented at three workshops on immigration and emigration at a 1982 conference on human rights. Addresses topics ranging from rights of refugees and migrants to philosophies of cultural pluralism. (KH)

  9. The Societal Integration of Immigrants in Germany

    OpenAIRE

    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...

  10. Chinese immigrants in Vancouver: quo vadis?

    OpenAIRE

    Guo, Shibao; DeVoretz, Don J.

    2006-01-01

    This paper reports findings from a Vancouver study which examines the settlement and adaptation experience of Chinese immigrants in Vancouver. The study reveals that non-economic reasons, such as the environment, education and citizenship, constituted the primary motivations for Chinese immigrants to move to Canada. Employment and language facilities were the most frequently cited barriers inhibiting their integration into the Vancouver social and economic spheres. Their poor economic perform...

  11. 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 th...... regimes of migration regulation the possibility of which is obscured by traditional justice approaches....

  12. [Portugal in the face of immigration].

    Science.gov (United States)

    Guibentif, P

    1996-01-01

    The relatively recent phenomenon of migration into Portugal is broken down into three components: foreign immigrants, return of emigrants, and repatriation of those from the old African colonies in Angola and Mozambique. Changes in the flow of migrants since 1960 are noted, and the economic and social situation of the various groups of immigrants is examined. Changes in public policies aimed at addressing migration-related issues are also discussed. (SUMMARY IN ENG AND SPA)

  13. News media consumption among immigrants in Europe

    DEFF Research Database (Denmark)

    Christiansen, Connie Carøe

    2004-01-01

    demonstrates that diaspora as an analytic term is indeed relevant for immigrants, leaving room for questions of multiple belonging with implications for everyday life. According to recent data, people with migrant experience tend to seek news very broadly. Extensive news media consumption, desire for more...... 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....

  14. Illness causal beliefs in Turkish immigrants

    OpenAIRE

    Klimidis Steven; Minas Harry; Tuncer Can

    2007-01-01

    Abstract Background People hold a wide variety of beliefs concerning the causes of illness. Such beliefs vary across cultures and, among immigrants, may be influenced by many factors, including level of acculturation, gender, level of education, and experience of illness and treatment. This study examines illness causal beliefs in Turkish-immigrants in Australia. Methods Causal beliefs about somatic and mental illness were examined in a sample of 444 members of the Turkish population of Melbo...

  15. African-American attitudes towards United States immigration policy.

    Science.gov (United States)

    Diamond, J

    1998-01-01

    In the growing US debate over immigration policy since the 1980s, it is often argued that immigration must be restricted in order to protect Black Americans from competition with newly arrived immigrants. Findings are reported upon Black Americans' attitudes toward immigration policy. An extensive review of more than 50 Black newspapers and magazines, from January 1994 to June 1996, uncovered attitudes both in favor of and against restricting immigration. The majority of articles in the Black press on immigration, however, were nonrestrictionist. The Black political leadership is also against restricting immigration. Furthermore, a review of the 14 most recent national opinion polls on immigration available to the Roper Center for Public Opinion Research as of July 1996 found that while many Blacks favor restricting immigration, all US Blacks should not be characterized as restrictionist, especially when compared with Whites. Historical attitudes among US Blacks dating back to before the abolition of slavery are discussed.

  16. Fertility behaviour of recent immigrants to Israel

    Directory of Open Access Journals (Sweden)

    2004-03-01

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

  17. 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

  18. 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…

  19. From Refugees to Immigrants: The Legalization Strategies of Salvadoran Immigrants and Activists.

    Science.gov (United States)

    Coutin, Susan Bibler

    1998-01-01

    Discusses issues of policy redefinition, legal categorization, and immigrants' agency by examining the legalization strategies pursued by Salvadoran immigrants from the 1980s to the present. Demonstrates how arguments were connected to United States . foreign policy, human-rights violations in Central America, and other political legal issues.…

  20. 76 FR 67361 - Visas: Documentation of Immigrants Under the Immigration and Nationality Act, as Amended

    Science.gov (United States)

    2011-11-01

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF STATE 22 CFR Part 42 RIN 1400-AC86 Visas: Documentation of Immigrants Under the Immigration and Nationality Act, as Amended AGENCY: State Department. ACTION: Interim final rule. SUMMARY: This rule amends the Department...

  1. 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

  2. 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…

  3. 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'…

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

    Science.gov (United States)

    Hossain, Kazi I.

    2014-01-01

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

  5. Immigration and violence: the offsetting effects of immigrant concentration on Latino violence.

    Science.gov (United States)

    Feldmeyer, Ben

    2009-09-01

    Despite longstanding interest in the effects of immigration on American society, there are few studies that examine the relationship between immigration and crime. Drawing from social disorganization theory and community resource/social capital perspectives, this study examines the effects of Latino immigration on Latino violence. Data on violence (i.e., homicide, robbery, and Violent Index) and the structural conditions of Latino populations are drawn from the California Arrest Data (CAL), New York State Arrest Data (NYSAD), and U.S. Census data for approximately 400 census places during the 1999-2001 period. Findings suggest that immigrant concentration has no direct effect on Latino homicide or Violent Index rates but may reduce Latino robbery. Immigration also appears to have multiple, offsetting indirect effects on Latino violence that work through social disorganization and community resource measures. These results suggest that (1) immigrant concentration does not contribute to Latino violence and may even reduce some forms of violence, (2) immigration simultaneously stabilizes and destabilizes structural conditions in Latino populations, and (3) it is useful to examine both the direct and indirect effects of immigration on crime.

  6. 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

  7. 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…

  8. Immigrants Families and Childcare Preferences: Do Immigrants' Cultures Influence Their Childcare Decisions?

    Science.gov (United States)

    Obeng, Cecilia Sem

    2007-01-01

    The author examines childcare preferences of African immigrant parents living in the United States. Based on interviews with eighteen parents with preschool-aged children and working within Bryman, Lewis-Beck, and Liao's (2004) narrative inquiry, the author demonstrates that although many of the African immigrants surveyed for the study preferred…

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

    Science.gov (United States)

    Enciso, Patricia

    2011-01-01

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

  10. Does Immigrant Employment Matter for Exports? Evidence From Denmark

    DEFF Research Database (Denmark)

    Hiller, Sanne

    evidence on the adjustment of firms’ product portfolio in response to immigration. Our results show that firms can reap the benefits from immigration only through hiring foreigners. This implies that the trade-cost reducing intercultural knowledge embedded in foreign expatriates can only be accessed via......Immigration impacts the economy in ample ways: it affects growth, wages and total factor productivity. This study deals with the effects of immigration on firm exports. Can firms benefit from hiring immigrants to expand their export sales? Or do immigrants who live in the firm’s region affect trade...

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

    DEFF Research Database (Denmark)

    Harmon, Nikolaj Arpe

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

  12. 76 FR 70735 - Privacy Act of 1974; Department of Homeland Security/U.S. Citizenship and Immigration Services...

    Science.gov (United States)

    2011-11-15

    ... Immigration Services--016 Electronic Immigration System-3 Automated Background Functions System of Records... and Immigration Services--016 Electronic Immigration System-3 Automated Background Functions System of... Immigration Services to collect and maintain certain biographic information about individuals in the...

  13. 76 FR 60059 - Privacy Act of 1974; Department of Homeland Security/U.S. Citizenship and Immigration Services...

    Science.gov (United States)

    2011-09-28

    ... Immigration Services--016 Electronic Immigration System-3 Automated Background Functions System of Records... and Immigration Services--016 Electronic Immigration System-3 Automated Background Functions System of... Immigration Services to collect and maintain certain biographic information about individuals in the...

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

    DEFF Research Database (Denmark)

    Norredam, M; Sheikh, A; Svendsen, K Dynnes;

    2016-01-01

    BACKGROUND: The impact of migration on the risk of anaphylaxis is unknown. We hypothesized that non-Western immigrants have a lower incidence of anaphylaxis compared to Danish-born. We investigated variations in hospital attendance for anaphylaxis between immigrants and Danish-born including time......- and age- trends. METHODS: A register-based, historical prospective cohort design. Refugees or family reunified immigrants (n=127,250) who, between January 1,1994 and December 31, 2010, obtained residency permits in Denmark were included and matched in a 1:6 ratio on age and sex with Danish...... for age using a Cox regression model including the influence of duration of residence and age when residence was obtained. RESULTS: In total 1,053 hospital attendances for anaphylaxis were identified: 89 among non-Western immigrants, 9 among Western immigrants and 955 among Danish-born patients. Both male...

  15. 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.

  16. 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;

    2015-01-01

    school composition and fighting was stronger for non-immigrants than in environments with high classmate support. In environments of low classmate support, the negative relationship between immigrant school composition and fighting and bullying victimization was stronger for immigrant adolescents than...... in environments with high classmate support. In general, the contribution of immigrant school composition was modest in comparison to the contribution of classmate support. The findings emphasize that it is not just the number of immigrants in a class per se, but rather the environment in the classroom which...

  17. A tumor suppressor C53 protein antagonizes checkpoint kinases to promote cyclin-dependent kinase 1 activation

    Science.gov (United States)

    Jiang, Hai; Wu, Jianchun; He, Chen; Yang, Wending; Li, Honglin

    2009-01-01

    Cyclin dependent kinase 1 (Cdk1)/cyclin B1 complex is the driving force for mitotic entry, and its activation is tightly regulated by the G2/M checkpoint. We originally reported that a novel protein C53 (also known as Cdk5rap3 and LZAP) potentiates DNA damage-induced cell death by modulating the G2/M checkpoint (1). More recently, Wang et al (2007) found that C53/LZAP may function as a tumor suppressor via inhibiting NF-κB signaling (2). We report here identification of C53 protein as a novel regulator of Cdk1 activation. We found that knockdown of C53 protein causes delayed Cdk1 activation and mitotic entry. During DNA damage response, activation of checkpoint kinase 1 and 2 (Chk1 and Chk2) is partially inhibited by C53 overexrepsssion. Intriguingly, we found that C53 interacts with checkpoint kinase 1 (Chk1) and antagonizes its function. Moreover, a portion of C53 protein is localized at the centrosome, and centrosome-targeting C53 potently promotes local Cdk1 activation. Taken together, our results strongly suggest that C53 is a novel negative regulator of checkpoint response. By counteracting Chk1, C53 promotes Cdk1 activation and mitotic entry in both unperturbed cell cycle progression and DNA damage response. PMID:19223857

  18. 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

  19. 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.

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

    Directory of Open Access Journals (Sweden)

    Pushpavalli Sreerangam NCVL

    2013-01-01

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

  2. Hepatitis B virus infection in immigrant populations

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Hepatitis B virus (HBV) is the most common cause ofhepatitis worldwide, with nearly 350 million peoplechronically infected and 600000 deaths per year dueto acute liver failure occurring during acute hepatitisor, more frequently, in HBV-related liver cirrhosis orhepatocellular carcinoma. Ongoing immigration fromcountries with a high HBV endemicity to those with a lowHBV endemicity warrants particular attention to preventthe spread of HBV infection to the native population.This review article analyzes the epidemiology andvirological and clinical characteristics of HBV infectionin immigrant populations and in their host countries,and suggests prophylactic measures to prevent thespread of this infection. Among the immigrants fromdifferent geographical areas, those from South East Asiaand sub-Saharan Africa show the highest prevalencesof hepatitis B surface antigen (HBsAg) carriers, inaccordance with the high endemicity of the countriesof origin. The molecular characteristics of HBV infectionin immigrants reflect those of the geographical areasof origin HBV genotype A and D predominate inimmigrants from Eastern Europe, B and C in those fromAsia and genotype E in those from Africa. The literaturedata on the clinical course and treatment of HBsAgpositiveimmigrants are scanty. The management ofHBV infection in immigrant populations is difficult andrequires expert personnel and dedicated structures fortheir assistance. The social services, voluntary operatorsand cultural mediators are essential to achieve optimizedpsychological and clinical intervention.

  3. 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.

  4. [Immigrants and dialysis: a survey in Piedmont].

    Science.gov (United States)

    Forneris, Giacomo; Boero, Roberto; Massara, Carlo; Quarello, Francesco

    2011-01-01

    The number of immigrants has been rapidly increasing in Italy in the last decade, with potentially profound effects on the national health care system. Yet, few data are available on the clinical and demographic features of these subjects, or on their need for nephrological care and dialysis treatment. A survey was conducted in 19 dialysis facilities of Piedmont (a northwestern Italian region) about immigrants on chronic dialysis treatment. Data on native country, administrative position, clinical and dialysis aspects were anonymously collected. Overall, 93 immigrant dialysis patients coming from 24 foreign countries were registered. Most of them were young (mean age 46∓14 years) and on extracorporeal treatment (87%); late referral (38%) or starting dialysis in emergency (17%) were common modalities of presentation. Glomerular (33%) or unknown (31%) nephropathies were the most representative causes of end stage renal disease. No difference in incidence of HCV, HBV and HIV compared with native Italian patients was observed. Notably, more than 50% of the immigrant patients had low-level knowledge of Italian. As regards administrative position, 69% were regular foreign citizens, 19% were temporary foreign workers, and 9% had a residence permit. Our survey confirms the existence of a young immigrant population on dialysis in Piedmont, whose social and relational problems are more challenging than clinical aspects and call for new organizational models to manage this growing population on dialysis.

  5. Immigration and use of psychoactive substances

    Directory of Open Access Journals (Sweden)

    Missouridou E.

    2016-01-01

    Full Text Available Introduction: In the context of deep economic and socio-cultural crisis and the massive influx of immigrants in our country, health professionals are called to meet the needs of immigrants who use psychoactive substances. Purpose: This study aims at investigating the problematic use of alcohol and drugs by immigrants and addressing effectively their needs. Method: Study of Greek and international literature from online databases and journals. Conclusions: Acculturation stress, high degree of acculturation and acculturation gap between different generations of immigrants are associated with high rates of addiction. In the case of new immigrants, who are experiencing the acculturation gap to the previous generation as well as the difficulty to establish an identity that synthesizes elements from both cultures , the subculture of use is often a way of seeking support which they are unable to find in their family or other cultural groups. The efforts to provide culturally competent care require self-knowledge and awareness related to beliefs, attitudes, and stereotypes about the culturally different at a both personal and collective level (organizations, cultural groups, society.

  6. BMI1 attenuates etoposide-induced G2/M checkpoints via reducing ATM activation.

    Science.gov (United States)

    Wei, F; Ojo, D; Lin, X; Wong, N; He, L; Yan, J; Xu, S; Major, P; Tang, D

    2015-06-04

    The BMI1 protein contributes to stem cell pluripotency and oncogenesis via multiple functions, including its newly identified role in DNA damage response (DDR). Although evidence clearly demonstrates that BMI1 facilitates the repair of double-stranded breaks via homologous recombination (HR), it remains unclear how BMI1 regulates checkpoint activation during DDR. We report here that BMI1 has a role in G2/M checkpoint activation in response to etoposide (ETOP) treatment. Ectopic expression of BMI1 in MCF7 breast cancer and DU145 prostate cancer cells significantly reduced ETOP-induced G2/M arrest. Conversely, knockdown of BMI1 in both lines enhanced the arrest. Consistent with ETOP-induced activation of the G2/M checkpoints via the ATM pathway, overexpression and knockdown of BMI1, respectively, reduced and enhanced ETOP-induced phosphorylation of ATM at serine 1981 (ATM pS1981). Furthermore, the phosphorylation of ATM targets, including γH2AX, threonine 68 (T68) on CHK2 (CHK2 pT68) and serine 15 (S15) on p53 were decreased in overexpression and increased in knockdown BMI1 cells in response to ETOP. In line with the requirement of NBS1 in ATM activation, we were able to show that BMI1 associates with NBS1 and that this interaction altered the binding of NBS1 with ATM. BMI1 consists of a ring finger (RF), helix-turn-helix-turn-helix-turn (HT), proline/serine (PS) domain and two nuclear localization signals (NLS). Although deletion of either RF or HT did not affect the association of BMI1 with NBS1, the individual deletions of PS and one NLS (KRMK) robustly reduced the interaction. Stable expression of these BMI1 mutants decreased ETOP-induced ATM pS1981 and CHK2 pT68, but not ETOP-elicited γH2AX in MCF7 cells. Furthermore, ectopic expression of BMI1 in non-transformed breast epithelial MCF10A cells also compromised ETOP-initiated ATM pS1981 and γH2AX. Taken together, we provide compelling evidence that BMI1 decreases ETOP-induced G2/M checkpoint activation via

  7. Status of Muslim Immigrants' Children with Learning Difficulties in Vienna

    Science.gov (United States)

    Mohsin, M. Naeem; Shabbir, Muhammad; Saeed, Wizra; Mohsin, M. Saleem

    2013-01-01

    The study was conducted to know the status of Muslim immigrants' children with learning difficulties and importance of parents' involvement for the education whose children are with learning difficulties, and the factors responsible for the learning difficulties among immigrants' children. There were 81 immigrant children with learning…

  8. Legal Status and Wage Disparities for Mexican Immigrants

    Science.gov (United States)

    Hall, Matthew; Greenman, Emily; Farkas, George

    2010-01-01

    This article employs a unique method of inferring the legal status of Mexican immigrants in the Survey of Income and Program Participation to offer new evidence of the role of legal authorization in the United States on workers' wages. We estimate wage trajectories for four groups: documented Mexican immigrants, undocumented Mexican immigrants,…

  9. U.S. Immigration: Trends and Implications for Schools.

    Science.gov (United States)

    Fix, Michael; Passel, Jeffrey S.

    This paper highlights three major aspects of recent trends in immigration and their impact on schools: high sustained flows, growing geographic dispersal, and an increase in undocumented immigration. It focuses on such topics as who comes to the United States (legal, humanitarian, and undocumented immigrants); demographic context (income level and…

  10. 32 CFR 700.860 - Customs and immigration inspections.

    Science.gov (United States)

    2010-07-01

    ... 32 National Defense 5 2010-07-01 2010-07-01 false Customs and immigration inspections. 700.860... Commanding Officer Commanding Officers Afloat § 700.860 Customs and immigration inspections. (a) The... a customs officer or immigration officer of the United States to make on board the ship or...

  11. Large Deviation for Supercritical Branching Processes with Immigration

    Institute of Scientific and Technical Information of China (English)

    Jing Ning LIU; Mei ZHANG

    2016-01-01

    In this paper, we study the large deviation for a supercritical branching process with immigration controlled by a sequence of non-negative integer-valued independently identical distributed random variables, improving the previous results for non immigration processes. We rely heavily on the detail description and limit property of the generating function of immigration processes.

  12. 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...

  13. 8 CFR 1240.50 - Decision of the immigration judge.

    Science.gov (United States)

    2010-01-01

    ... 8 Aliens and Nationality 1 2010-01-01 2010-01-01 false Decision of the immigration judge. 1240.50 Section 1240.50 Aliens and Nationality EXECUTIVE OFFICE FOR IMMIGRATION REVIEW, DEPARTMENT OF JUSTICE IMMIGRATION REGULATIONS PROCEEDINGS TO DETERMINE REMOVABILITY OF ALIENS IN THE UNITED STATES Proceedings...

  14. 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...

  15. 76 FR 73475 - Immigration Benefits Business Transformation, Increment I; Correction

    Science.gov (United States)

    2011-11-29

    ..., 207, 208, 211, 212, 213a, 244; 245, 324; 335 RIN 1615-AB83 Immigration Benefits Business Transformation, Increment I; Correction AGENCY: U.S. Citizenship and Immigration Services, DHS. ACTION: Final... to enable U.S. Citizenship and Immigration Services (USCIS) to transform its business processes....

  16. 78 FR 22770 - Immigration Benefits Business Transformation, Increment I; Correction

    Science.gov (United States)

    2013-04-17

    ... SECURITY 8 CFR Parts 103 and 208 RIN 1615-AB83 Immigration Benefits Business Transformation, Increment I; Correction AGENCY: U.S. Citizenship and Immigration Services, Department of Homeland Security. ACTION... final rule to amend DHS regulations to enable U.S. Citizenship and Immigration Services (USCIS)...

  17. 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...

  18. Challenging Anti-Immigration Discourses in School and Community Contexts

    Science.gov (United States)

    Allexsaht-Snider, Martha; Buxton, Cory A.; Harman, Ruth

    2012-01-01

    Rapid migration shifts, anti-immigrant discourses in the public sphere, and harsh immigration policies have posed daunting challenges for immigrant students, their families, their teachers, and their communities in the 21st century. Trends in public discourse and law enforcement in the United States mirror developments in European countries with…

  19. Immigration, "Any Small Goodness," and Integrated Social Studies

    Science.gov (United States)

    Bauml, Michelle; Field, Sherry L.; Ledbetter, Mary

    2013-01-01

    Mary Ledbetter's fifth grade students at the University of Texas Elementary School know immigration well. Some of them are recent immigrants from Mexico, or they have family members who are. Several of Mary's students are first or second generation Americans. For Mary, immigration is one of the most important units she teaches, one that integrates…

  20. 28 CFR 16.84 - Exemption of Immigration Appeals System.

    Science.gov (United States)

    2010-07-01

    ... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Exemption of Immigration Appeals System... MATERIAL OR INFORMATION Exemption of Records Systems Under the Privacy Act § 16.84 Exemption of Immigration...) Decisions of the Board of Immigration Appeals (JUSTICE/BIA-001). This exemption applies only to the...

  1. 8 CFR 235.6 - Referral to immigration judge.

    Science.gov (United States)

    2010-01-01

    ... 8 Aliens and Nationality 1 2010-01-01 2010-01-01 false Referral to immigration judge. 235.6 Section 235.6 Aliens and Nationality DEPARTMENT OF HOMELAND SECURITY IMMIGRATION REGULATIONS INSPECTION OF PERSONS APPLYING FOR ADMISSION § 235.6 Referral to immigration judge. (a) Notice—(1) Referral by Form...

  2. 8 CFR 1240.31 - Authority of immigration judges.

    Science.gov (United States)

    2010-01-01

    ... 8 Aliens and Nationality 1 2010-01-01 2010-01-01 false Authority of immigration judges. 1240.31 Section 1240.31 Aliens and Nationality EXECUTIVE OFFICE FOR IMMIGRATION REVIEW, DEPARTMENT OF JUSTICE IMMIGRATION REGULATIONS PROCEEDINGS TO DETERMINE REMOVABILITY OF ALIENS IN THE UNITED STATES Exclusion...

  3. 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....

  4. 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...

  5. 76 FR 63321 - U.S. Citizenship and Immigration Services

    Science.gov (United States)

    2011-10-12

    ...-63322] [FR Doc No: 2011-26361] DEPARTMENT OF HOMELAND SECURITY U.S. Citizenship and Immigration Services... Under Review: E-Verify Program. The Department of Homeland Security, U.S. Citizenship and Immigration... and Immigration Services. (4) Affected public who will be asked or required to respond, as well as...

  6. 8 CFR 1240.12 - Decision of the immigration judge.

    Science.gov (United States)

    2010-01-01

    ... 8 Aliens and Nationality 1 2010-01-01 2010-01-01 false Decision of the immigration judge. 1240.12 Section 1240.12 Aliens and Nationality EXECUTIVE OFFICE FOR IMMIGRATION REVIEW, DEPARTMENT OF JUSTICE IMMIGRATION REGULATIONS PROCEEDINGS TO DETERMINE REMOVABILITY OF ALIENS IN THE UNITED STATES...

  7. Parables and Politics: Clergy Attitudes toward Illegal Immigration in Alabama

    Science.gov (United States)

    Wickersham, Mary Eleanor

    2013-01-01

    The passage of a stringent immigration law in Alabama in 2011 makes relevant the juxtaposition of clergy and congregant attitudes and behaviors toward illegal immigrants as related to Biblical teachings that require charity to aliens. In order to examine the relationship between religious attitudes and illegal immigration, approximately 426…

  8. Malaria clusters among illegal Chinese immigrants to Europe through Africa.

    Science.gov (United States)

    Bisoffi, Zeno; Matteelli, Alberto; Aquilini, Donatella; Guaraldi, Giovanni; Magnani, Giacomo; Orlando, Giovanna; Gaiera, Giovanni; Jelinek, Tomas; Behrens, Ron H

    2003-09-01

    Between November 2002 and March 2003, 17 cases of malaria (1 fatal) were observed in illegal Chinese immigrants who traveled to Italy through Africa. A further cluster of 12 was reported in August, 2002. Several immigrants traveled by air, making the risk of introducing sudden acute respiratory syndrome a possibility should such illegal immigrations continue.

  9. Punjabi Orchard Farmers: An Immigrant Enclave in Rural California.

    Science.gov (United States)

    Gibson, Margaret A.

    1988-01-01

    Examines the adaptation patterns of Punjabi Sikh orchard farmers in rural California. Discusses the role of the following: (1) the historical context of immigration; (2) the immigrants' perceptions of their particular situation; (3) the group's cultural traditions; and (4) 1965 Immigration Act. (FMW)

  10. Immigration in Childhood: Using Picture Books to Cope

    Science.gov (United States)

    Baghban, Marcia

    2007-01-01

    The United States is currently experiencing the largest wave of immigration in its history. This contemporary immigration is unprecedented in its diversity of ethnicity, class, and countries of origin, and large urban areas are no longer alone in absorbing arrivals. The author reviews children's picture books about dilemmas that immigrant children…

  11. The Educational Attainment of Second Generation Immigrants in the Netherlands

    NARCIS (Netherlands)

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

    2001-01-01

    Since the mid-1960's the Netherlands has had an immigration surplus, mainly because of manpower recruitment from Turkey and Morocco and immigration from the former Dutch colony of Surinam.Immigrants have a weak labor market position, which is related to their educational level and language skills.Ch

  12. 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....

  13. The Economics of U.S. Immigration Policy

    Science.gov (United States)

    Orrenius, Pia M.; Zavodny, Madeline

    2012-01-01

    The economic gains from immigration are much like those from international trade: The economy benefits overall from immigration, but there are distributional effects that create both winners and losers. Immigration is different from trade, however, in that the physical presence of the people who provide the goods and services that drive the…

  14. Gender, Acculturation, Food Patterns, and Overweight in Korean Immigrants

    Science.gov (United States)

    Jasti, Sunitha; Lee, Chang Hyun; Doak, Colleen

    2011-01-01

    Objective: To describe acculturation, food patterns, overweight, and gender differences among Korean immigrants in the United States. Methods: A cross-sectional exploratory survey assessed acculturation, food frequencies, and weight status of 195 Korean immigrants. Results: Acculturated Korean immigrants (score greater than or equal to] 2.5) were…

  15. Acculturation gaps in Vietnamese immigrant families: Impact on family relationships

    OpenAIRE

    Ho, Joyce; Birman, Dina

    2010-01-01

    Vietnamese immigrants in the United States face acculturation challenges involving the individual, family, and community. Experts suggest that immigrant family members acculturate at different rates resulting in an acculturation gap, which negatively influences family adjustment. In this study we examined the degree and patterns of acculturation differences between 104 first generation immigrant Vietnamese adolescents and their parents, and whether acculturation gap affected family relationsh...

  16. Immigrant Parents: How to Help Your Children Succeed in School

    Science.gov (United States)

    Md-Yunus, Sham'ah

    2008-01-01

    One of the top reasons immigrants give for coming to the United States is a desire to provide better educational and economic opportunities for their families and children. Immigrants voice this sentiment regardless of their educational level, financial standing, or country of origin. Immigrant children express the same intentions about education…

  17. L'immigration au Luxembourg, et après?

    OpenAIRE

    Parsons, Craig; Smeeding, Timothy

    2004-01-01

    The importance of immigration to the future of Europe and also to the future of Luxembourg cannot be denied. This paper presents Luxembourg both in the context of European immigration and also in comparative income inequality terms. The paper includes an assessment of why Luxembourg presents a unique but powerful example of successful European immigration: one of growth with diversity and equality.

  18. Culturally Speaking: Immigrant Authors Writing for Young Readers

    Science.gov (United States)

    York, Sherry

    2008-01-01

    Inspired by the memory of a student shot and killed due to suspicion that he was an illegal immigrant, the author has compiled a bibliography of books written by immigrants or their descendents. These books, based on family experiences that include the immigrant experience, can add richness and diversity to U.S. children's literature.

  19. Analysis of the tolerance to DNA alkylating damage in MEC1 and RAD53 checkpoint mutants of Saccharomyces cerevisiae.

    Directory of Open Access Journals (Sweden)

    Alfonso Gallego-Sánchez

    Full Text Available Checkpoint response, tolerance and repair are three major pathways that eukaryotic cells evolved independently to maintain genome stability and integrity. Here, we studied the sensitivity to DNA damage in checkpoint-deficient budding yeast cells and found that checkpoint kinases Mec1 and Rad53 may modulate the balance between error-free and error-prone branches of the tolerance pathway. We have consistently observed that mutation of the RAD53 counterbalances error-free and error-prone branches upon exposure of cells to DNA damage induced either by MMS alkylation or by UV-radiation. We have also found that the potential Mec1/Rad53 balance modulation is independent from Rad6/Rad18-mediated PCNA ubiquitylation, as mec1Δ or rad53Δ mutants show no defects in the modification of the sliding clamp, therefore, we infer that it is likely exerted by acting on TLS polymerases and/or template switching targets.

  20. Interpersonal violence among immigrants in Portugal.

    Science.gov (United States)

    Dias, Sónia; Fraga, Sílvia; Barros, Henrique

    2013-02-01

    To assess prevalence of interpersonal violence among a mixed gender sample of immigrants in Portugal, describing the type of violence and associated factors. A cross-sectional study was conducted between October 2008 and May 2009, evaluating a sample of 702 immigrants residing in the Lisbon region. Information was obtained by trained interviewers using a structured questionnaire. Overall, 15.1 % (15.5 % females and 14.7 % males; p = 0.844) of the immigrants reported to be victims of at least one episode of violence during the last year, regardless of which type of violence was involved. The prevalence of intimate-partner violence was 4.1 %, and it was significantly higher among women than men (7.1 % vs. 0.9 %, respectively, p Portugal, with different gender patterns regarding the perpetrators and settings of abuse.

  1. NEW PERSPECTIVES ON IMMIGRANT CONTEXTS OF RECEPTION

    Science.gov (United States)

    Levitt, Peggy; Cadge, Wendy; Hejtmanek, Jessica; Curran, Sara R.

    2014-01-01

    We argue that important, overlooked differences in what we call the ‘cultural armature’ of Portland, Maine, and Danbury, Connecticut help explain the variation in how each city received new immigrants in recent years. Portland has a long history of contact with the outside world and used its cosmopolitan character to promote urban redevelopment and welcome immigrants from a range of countries of origin. Danbury’s small-town, insular outlook, and the fact that most of its newcomers came from a single country of origin – some without legal documents – made immigrants’ welcome more fragmented. While leaders in both cities speak of multiculturalism and tolerance, the ‘cultural armature’ of each led city leaders to put that talk into action differently. We describe how we see this ‘cultural armature’ at work and argue that it – in combination with demographic realities – led immigrants to be more warmly welcomed in Portland than in Danbury. PMID:25383102

  2. Immigrant community integration in world cities

    CERN Document Server

    Lamanna, Fabio; Salas-Olmedo, María Henar; Romanillos, Gustavo; Gonçalves, Bruno; Ramasco, José J

    2016-01-01

    Migrant and hosting communities face long-term challenges in the integration process. Immigrants must adapt to new laws and ways of life, while hosts need to adjust to multicultural societies. Integration impacts many facets of life such as access to jobs, real state and public services and can be well approximated by the extent of spatial segregation of minority group residence. Here we conduct an extensive study of immigrant integration in 53 world cities by using Twitter language detection and by introducing metrics of spatial segregation. In this way, we quantify the Power of Integration of cities (their capacity to integrate diverse cultures), and characterize the relations between cultures when they act in the role of hosts and immigrants.

  3. [Foreign immigration in Spain (1985-1994)].

    Science.gov (United States)

    Gozalvez Perez, V

    1996-01-01

    "During the decade 1985-94, Spain [has had]...some growing and unexpected flows of foreign immigrations. The tradition of emigration of Spanish people, some grave difficulties of [the] employment market in the country, irregular entrance of workers from developing countries, the fear of a very rapid growth of these immigrants, the instability and marginality of their work, and the agreement of Spain in the European Union have led the government to develop an active migratory policy, first against the illegal flows and, more recently, in direction of the integration of immigrants in Spanish society.... The article analyzes main features from some different groups of foreign workers, and in particular Africans: spatial repartition, demographic profile, migratory strategies and trajectories, uneasy insertion in the national employment market, and draws lastly the main features of the Spanish migratory policy." (SUMMARY IN ENG AND SPA)

  4. IMMIGRATION GROWTH TENDENCIES IN OECD COUNTRIES

    Directory of Open Access Journals (Sweden)

    Imran SARIHASAN

    2016-12-01

    Full Text Available Immigration became one of the relevant economic topics in recent years. Over the centuries millions of people have migrated, despite the physical, cultural etc. obstacles, to other lands in search of better lives for themselves and their children. In the context of development, globalization and labor market mobility, it is necessary to further analyze the determinants and consequences of migration not only on the host country, but also on the sending country. The increased interest and availability of data keeps this subject in the attention of economists all over the world. In this case an increase in immigration became very significant ıssue for policymakers. The aims of this study are to describe immigration growth tendencies and to answer how much is the average growth rate of foreıgn born population. Thus, in order to measure the native and foreign-born unemployed migrants, twenty-seven OECD countries were used in this research paper.

  5. Immigration and welfare state cash benefits

    DEFF Research Database (Denmark)

    Pedersen, Peder J.

    2013-01-01

    estimation on the impact on welfare dependence from individual background factors. Findings – The main finding is the importance of aggregate low unemployment for immigrants to assimilate out of welfare dependence. Fairly small effects are reported from policy changes intending to influence the economic......Purpose – The purpose of this paper is to summarize existing evidence on welfare dependence among immigrants in Denmark and to produce new evidence with focus on the most recent years. Design/methodology/approach – The paper combines a broad descriptive/analytical approach with multivariate...... is the finding, at a disaggregate level, of how changes in immigration policy and cyclical changes interact, influencing the assimilation into or out of dependence on cash benefit programs....

  6. Does immigration boost per capita income?

    DEFF Research Database (Denmark)

    Felbermayr, Gabriel; Hiller, Sanne; Sala, Davide

    2010-01-01

    Using a cross-section of countries, we adapt Frankel and Romer's (1999) IV strategy to international labor mobility. Controlling for institutional quality, trade, and financial openness, we establish a robust and non-negative causal effect of immigration on real per capita income.......Using a cross-section of countries, we adapt Frankel and Romer's (1999) IV strategy to international labor mobility. Controlling for institutional quality, trade, and financial openness, we establish a robust and non-negative causal effect of immigration on real per capita income....

  7. Does Immigration Boost Per Capita Income?

    DEFF Research Database (Denmark)

    Felbermayr, Gabriel J.; Hiller, Sanne; Sala, Davide

    Using a cross-section of countries, we adapt Frankel and Romer's (1999) IV strategy to international labor mobility. Controlling for institutional quality, trade, and ?nancial openness, we establish a robust and non-negative causal e?ect of immigration on real per-capita income.......Using a cross-section of countries, we adapt Frankel and Romer's (1999) IV strategy to international labor mobility. Controlling for institutional quality, trade, and ?nancial openness, we establish a robust and non-negative causal e?ect of immigration on real per-capita income....

  8. Immigrant Integration: Acculturation and Social Integration

    Directory of Open Access Journals (Sweden)

    Astrid HAMBERGER

    2009-11-01

    Full Text Available This article tackles the concept of “immigrant integration” as it is analyzed by different authors in the international migration field. In this article, I will use the terms “refugee” and “immigrant” as equivalent to each other due to the interchangeable character of these concepts throughout the integration literature. First, the article brings into discussion the definitional and conceptual battle around the concept of immigrant “integration”, and second, it will describe and analyze cultural and social integration with their presupposing processes.

  9. Territorial Rights, Political Association, and Immigration

    DEFF Research Database (Denmark)

    Lægaard, Sune

    2013-01-01

    is therefore in need of additional justification. The paper considers Christopher Heath Wellman’s liberal proposal for justifying the right to control immigration, which understands the right as derivative of a general right to freedom of association held collectively by the people of the state. The paper...... argues that state legitimacy and freedom of political association fail to connect in the way required to justify a right to control immigration. Wellman’s argument conflates the state as an institution and the people as a political collective and elides the difference between territorial jurisdiction...

  10. A tumor suppressor C53 protein antagonizes checkpoint kinases to promote cyclin-dependent kinase 1 activation

    OpenAIRE

    Jiang, Hai; Wu, Jianchun; He, Chen; Yang, Wending; Li, Honglin

    2009-01-01

    Cyclin dependent kinase 1 (Cdk1)/cyclin B1 complex is the driving force for mitotic entry, and its activation is tightly regulated by the G2/M checkpoint. We originally reported that a novel protein C53 (also known as Cdk5rap3 and LZAP) potentiates DNA damage-induced cell death by modulating the G2/M checkpoint (1). More recently, Wang et al (2007) found that C53/LZAP may function as a tumor suppressor via inhibiting NF-κB signaling (2). We report here identification of C53 protein as a novel...

  11. 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.

  12. Engagement in self-regulated deep learning of successful immigrant and non-immigrant students in inner city schools

    NARCIS (Netherlands)

    Blom, S.; Severiens, S.

    2008-01-01

    In order to examine and explain differences in self-regulated (SR) deep learning of successful immigrant and non-immigrant students we investigated a population of 650 high track 10th grade students in Amsterdam, of which 39% had an immigrant background. By means of a questionnaire based on the MSLQ

  13. Engagement in Self-Regulated Deep Learning of Successful Immigrant and Non-Immigrant Students in Inner City Schools

    Science.gov (United States)

    Blom, Sarah; Severiens, Sabine

    2008-01-01

    In order to examine and explain differences in self-regulated (SR) deep learning of successful immigrant and non-immigrant students we investigated a population of 650 high track 10th grade students in Amsterdam, of which 39% had an immigrant background. By means of a questionnaire based on the MSLQ of Pintrich and De Groot (1990) the students…

  14. 8 CFR 1337.2 - Oath administered by the Immigration and Naturalization Service or an Immigration Judge.

    Science.gov (United States)

    2010-01-01

    ... 8 Aliens and Nationality 1 2010-01-01 2010-01-01 false Oath administered by the Immigration and Naturalization Service or an Immigration Judge. 1337.2 Section 1337.2 Aliens and Nationality EXECUTIVE OFFICE FOR IMMIGRATION REVIEW, DEPARTMENT OF JUSTICE NATIONALITY REGULATIONS OATH OF ALLEGIANCE § 1337.2...

  15. 8 CFR 337.2 - Oath administered by the Immigration and Naturalization Service or an Immigration Judge.

    Science.gov (United States)

    2010-01-01

    ... 8 Aliens and Nationality 1 2010-01-01 2010-01-01 false Oath administered by the Immigration and Naturalization Service or an Immigration Judge. 337.2 Section 337.2 Aliens and Nationality DEPARTMENT OF HOMELAND SECURITY NATIONALITY REGULATIONS OATH OF ALLEGIANCE § 337.2 Oath administered by the Immigration...

  16. Error-prone mammalian female meiosis from silencing the spindle assembly checkpoint without normal interkinetochore tension.

    Science.gov (United States)

    Kolano, Agnieszka; Brunet, Stéphane; Silk, Alain D; Cleveland, Don W; Verlhac, Marie-Hélène

    2012-07-03

    It is well established that chromosome segregation in female meiosis I (MI) is error-prone. The acentrosomal meiotic spindle poles do not have centrioles and are not anchored to the cortex via astral microtubules. By Cre recombinase-mediated removal in oocytes of the microtubule binding site of nuclear mitotic apparatus protein (NuMA), which is implicated in anchoring microtubules at poles, we determine that without functional NuMA, microtubules lose connection to MI spindle poles, resulting in highly disorganized early spindle assembly. Subsequently, very long spindles form with hyperfocused poles. The kinetochores of homologs make attachments to microtubules in these spindles but with reduced tension between them and accompanied by alignment defects. Despite this, the spindle assembly checkpoint is normally silenced and the advance to anaphase I and first polar body extrusion takes place without delay. Females without functional NuMA in oocytes are sterile, producing aneuploid eggs with altered chromosome number. These findings establish that in mammalian MI, the spindle assembly checkpoint is unable to sustain meiotic arrest in the presence of one or few misaligned and/or misattached kinetochores with reduced interkinetochore tension, thereby offering an explanation for why MI in mammals is so error-prone.

  17. Probing the Mec1ATR Checkpoint Activation Mechanism with Small Peptides.

    Science.gov (United States)

    Wanrooij, Paulina H; Tannous, Elias; Kumar, Sandeep; Navadgi-Patil, Vasundhara M; Burgers, Peter M

    2016-01-01

    Yeast Mec1, the ortholog of human ATR, is the apical protein kinase that initiates the cell cycle checkpoint in response to DNA damage and replication stress. The basal activity of Mec1 kinase is activated by cell cycle phase-specific activators. Three distinct activators stimulate Mec1 kinase using an intrinsically disordered domain of the protein. These are the Ddc1 subunit of the 9-1-1 checkpoint clamp (ortholog of human and Schizosaccharomyces pombe Rad9), the replication initiator Dpb11 (ortholog of human TopBP1 and S. pombe Cut5), and the multifunctional nuclease/helicase Dna2. Here, we use small peptides to determine the requirements for Mec1 activation. For Ddc1, we identify two essential aromatic amino acids in a hydrophobic environment that when fused together are proficient activators. Using this increased insight, we have been able to identify homologous motifs in S. pombe Rad9 that can activate Mec1. Furthermore, we show that a 9-amino acid Dna2-based peptide is sufficient for Mec1 activation. Studies with mutant activators suggest that binding of an activator to Mec1 is a two-step process, the first step involving the obligatory binding of essential aromatic amino acids to Mec1, followed by an enhancement in binding energy through interactions with neighboring sequences.

  18. Role of Intrinsic and Extrinsic Factors in the Regulation of the Mitotic Checkpoint Kinase Bub1.

    Directory of Open Access Journals (Sweden)

    Claudia Breit

    Full Text Available The spindle assembly checkpoint (SAC monitors microtubule attachment to kinetochores to ensure accurate sister chromatid segregation during mitosis. The SAC members Bub1 and BubR1 are paralogs that underwent significant functional specializations during evolution. We report an in-depth characterization of the kinase domains of Bub1 and BubR1. BubR1 kinase domain binds nucleotides but is unable to deliver catalytic activity in vitro. Conversely, Bub1 is an active kinase regulated by intra-molecular phosphorylation at the P+1 loop. The crystal structure of the phosphorylated Bub1 kinase domain illustrates a hitherto unknown conformation of the P+1 loop docked into the active site of the Bub1 kinase. Both Bub1 and BubR1 bind Bub3 constitutively. A hydrodynamic characterization of Bub1:Bub3 and BubR1:Bub3 demonstrates both complexes to have 1:1 stoichiometry, with no additional oligomerization. Conversely, Bub1:Bub3 and BubR1:Bub3 combine to form a heterotetramer. Neither BubR1:Bub3 nor Knl1, the kinetochore receptor of Bub1:Bub3, modulate the kinase activity of Bub1 in vitro, suggesting autonomous regulation of the Bub1 kinase domain. We complement our study with an analysis of the Bub1 substrates. Our results contribute to the mechanistic characterization of a crucial cell cycle checkpoint.

  19. An Adaptive Checkpointing Scheme for Peer-to-Peer Based Volunteer Computing Work Flows

    CERN Document Server

    Ni, Lei

    2007-01-01

    Volunteer Computing, sometimes called Public Resource Computing, is an emerging computational model that is very suitable for work-pooled parallel processing. As more complex grid applications make use of work flows in their design and deployment it is reasonable to consider the impact of work flow deployment over a Volunteer Computing infrastructure. In this case, the inter work flow I/O can lead to a significant increase in I/O demands at the work pool server. A possible solution is the use of a Peer-to- Peer based parallel computing architecture to off-load this I/O demand to the workers; where the workers can fulfill some aspects of work flow coordination and I/O checking, etc. However, achieving robustness in such a large scale system is a challenging hurdle towards the decentralized execution of work flows and general parallel processes. To increase robustness, we propose and show the merits of using an adaptive checkpoint scheme that efficiently checkpoints the status of the parallel processes accordin...

  20. Differences in spindle association of the mitotic checkpoint protein Mad2 in mammalian spermatogenesis and oogenesis.

    Science.gov (United States)

    Kallio, M; Eriksson, J E; Gorbsky, G J

    2000-09-01

    We have investigated expression and subcellular localization of the spindle checkpoint protein Mad2 during rat and mouse spermatogenesis and in superovulated mouse oocytes. Our immunofluorescence studies demonstrate substantial differences in the localization patterns of kinetochore-associated Mad2 in these meiotic systems compared with previous studies of mitosis. In addition, the association of Mad2 with second-division-metaphase kinetochores differed significantly in male versus female meiosis. In spermatogenesis, Mad2 remained at most kinetochores throughout the entire first meiotic division and was lost only at metaphase of the second meiotic division. This result indicates that loss of kinetochore-associated Mad2 is not essential for the metaphase-to-anaphase transition during the first meiotic division. Disruption of the male meiotic spindles with the microtubule depolymerizing agent nocodazole resulted in the appearance of Mad2 at nearly all kinetochores. In contrast, the microtubule stabilizer taxol induced the loss of Mad2 from the majority of the first-division-metaphase kinetochores in which it was normally present in untreated cells. In contrast to the situation in spermatogenesis, Mad2 persisted at the kinetochores of normal, second-division oocytes at metaphase. These findings suggest that the role of the kinetochore in signaling in the spindle checkpoint may differ markedly between mammalian mitosis and meiosis, between the two meiotic divisions, and between male and female meiosis.

  1. Estimated Interval-Based Checkpointing (EIC on Spot Instances in Cloud Computing

    Directory of Open Access Journals (Sweden)

    Daeyong Jung

    2014-01-01

    Full Text Available In cloud computing, users can rent computing resources from service providers according to their demand. Spot instances are unreliable resources provided by cloud computing services at low monetary cost. When users perform tasks on spot instances, there is an inevitable risk of failures that causes the delay of task execution time, resulting in a serious deterioration of quality of service (QoS. To deal with the problem on spot instances, we propose an estimated interval-based checkpointing (EIC using weighted moving average. Our scheme sets the thresholds of price and execution time based on history. Whenever the actual price and the execution time cross over the thresholds, the system saves the state of spot instances. The Bollinger Bands is adopted to inform the ranges of estimated cost and execution time for user's discretion. The simulation results reveal that, compared to the HBC and REC, the EIC reduces the number of checkpoints and the rollback time. Consequently, the task execution time is decreased with EIC by HBC and REC. The EIC also provides the benefit of the cost reduction by HBC and REC, on average. We also found that the actual cost and execution time fall within the estimated ranges suggested by the Bollinger Bands.

  2. The Transcription Factor E4F1 Coordinates CHK1-Dependent Checkpoint and Mitochondrial Functions

    Directory of Open Access Journals (Sweden)

    Geneviève Rodier

    2015-04-01

    Full Text Available Recent data support the notion that a group of key transcriptional regulators involved in tumorigenesis, including MYC, p53, E2F1, and BMI1, share an intriguing capacity to simultaneously regulate metabolism and cell cycle. Here, we show that another factor, the multifunctional protein E4F1, directly controls genes involved in mitochondria functions and cell-cycle checkpoints, including Chek1, a major component of the DNA damage response. Coordination of these cellular functions by E4F1 appears essential for the survival of p53-deficient transformed cells. Acute inactivation of E4F1 in these cells results in CHK1-dependent checkpoint deficiency and multiple mitochondrial dysfunctions that lead to increased ROS production, energy stress, and inhibition of de novo pyrimidine synthesis. This deadly cocktail leads to the accumulation of uncompensated oxidative damage to proteins and extensive DNA damage, ending in cell death. This supports the rationale of therapeutic strategies simultaneously targeting mitochondria and CHK1 for selective killing of p53-deficient cancer cells.

  3. Role of Clinical Pharmacology in the Development and Approval of Immunotherapies Targeting Immune Checkpoints.

    Science.gov (United States)

    Rahman, A

    2016-12-01

    Immune surveillance plays a critical role in preventing the development and progression of cancer. Immune modulators, such as interferon-gamma or interleukin-2, have been a part of the cancer treatment armament over the past few decades. However, new understandings regarding the role of the costimulatory and coinhibitory molecules associated with T-cells and antigen-presenting cells as well as tumor necrosis factor receptors and ligands have ushered the new era of immunotherapy for cancer treatment. We now know that primary cancer cells evade screening by the innate immune system, proliferate, and form metastases by upregulating immune inhibitory pathways referred to as immune checkpoints. The recent development of therapies that target immune checkpoints, such as cytotoxic T lymphocyte antigen 4, programmed cell death 1, programmed cell death ligand 1, indoleamine 2,3-dioxygenase, T-cell immunoglobulin and mucin domain 3, and lymphocyte activation gene 3 precisely target the immune system and give new hope for treating various types of cancer. In select marker-enriched populations, immunotherapies provide high response rates as well as durable responses in terms of progression-free survival and overall survival. Numerous factors, such as patient's immune system, the expression of targets on both immune and cancer cells, maintenance of an effective drug exposure, and tolerability to these agents may play a role in this unique observation.

  4. Histone deacetylase inhibitors promote glioma cell death by G2 checkpoint abrogation leading to mitotic catastrophe.

    Science.gov (United States)

    Cornago, M; Garcia-Alberich, C; Blasco-Angulo, N; Vall-Llaura, N; Nager, M; Herreros, J; Comella, J X; Sanchis, D; Llovera, M

    2014-10-02

    Glioblastoma multiforme is resistant to conventional anti-tumoral treatments due to its infiltrative nature and capability of relapse; therefore, research efforts focus on characterizing gliomagenesis and identifying molecular targets useful on therapy. New therapeutic strategies are being tested in patients, such as Histone deacetylase inhibitors (HDACi) either alone or in combination with other therapies. Here two HDACi included in clinical trials have been tested, suberanilohydroxamic acid (SAHA) and valproic acid (VPA), to characterize their effects on glioma cell growth in vitro and to determine the molecular changes that promote cancer cell death. We found that both HDACi reduce glioma cell viability, proliferation and clonogenicity. They have multiple effects, such as inducing the production of reactive oxygen species (ROS) and activating the mitochondrial apoptotic pathway, nevertheless cell death is not prevented by the pan-caspase inhibitor Q-VD-OPh. Importantly, we found that HDACi alter cell cycle progression by decreasing the expression of G2 checkpoint kinases Wee1 and checkpoint kinase 1 (Chk1). In addition, HDACi reduce the expression of proteins involved in DNA repair (Rad51), mitotic spindle formation (TPX2) and chromosome segregation (Survivin) in glioma cells and in human glioblastoma multiforme primary cultures. Therefore, HDACi treatment causes glioma cell entry into mitosis before DNA damage could be repaired and to the formation of an aberrant mitotic spindle that results in glioma cell death through mitotic catastrophe-induced apoptosis.

  5. Checkpoint for DNA integrity at the first mitosis after oocyte activation.

    Science.gov (United States)

    Liu, Lin; Trimarchi, James R; Smith, Peter J S; Keefe, David L

    2002-06-01

    Activation of oocytes, arrested at the meiosis II (MII) in mammals, initiates meiotic release, mitotic divisions, and development. Unlike most somatic cell types, MII arrested female germ cells lack an efficient DNA integrity checkpoint control. Here we present evidence showing a unique checkpoint for DNA integrity at first mitosis after oocyte activation. Mouse oocytes carrying intact DNA cleaved normally after meiotic release, whereas 50% of oocytes harboring damaged DNA manifested cytofragmentation, a morphological hallmark of apoptosis. If not activated, DNA-damaged MII oocytes did not show apoptotic fragmentation. Further, activated, enucleated oocytes or enucleated fertilized oocytes also underwent cytofragmentation, implicating cytoplasmic coordination of the fragmentation process, independent of the nucleus. Depolymerization of either actin filaments or microtubules induced no cytofragmentation, but inhibited fragmentation upon oocyte activation. During the process of fragmentation, microtubule networks formed, then microtubule asters congregated at discrete locations, around which fragmented cellular bodies formed. Mitotic spindles, however, were not formed inactivated oocytes with damaged or absent DNA; in contrast, normal mitotic spindles were formed in activated oocytes with intact DNA. These results demonstrate that damaged DNA or absence of DNA leads to cytofragmentation after oocyte activation. Further, we found a mechanism of cytoskeletal involvement in the process of cytofragmentation. In addition, possible implication of the present findings in somatic cell cloning and human clinical embryology is discussed.

  6. Choreography of the DNA damage response: spatiotemporal relationships among checkpoint and repair proteins.

    Science.gov (United States)

    Lisby, Michael; Barlow, Jacqueline H; Burgess, Rebecca C; Rothstein, Rodney

    2004-09-17

    DNA repair is an essential process for preserving genome integrity in all organisms. In eukaryotes, recombinational repair is choreographed by multiprotein complexes that are organized into centers (foci). Here, we analyze the cellular response to DNA double-strand breaks (DSBs) and replication stress in Saccharomyces cerevisiae. The Mre11 nuclease and the ATM-related Tel1 kinase are the first proteins detected at DSBs. Next, the Rfa1 single-strand DNA binding protein relocalizes to the break and recruits other key checkpoint proteins. Later and only in S and G2 phase, the homologous recombination machinery assembles at the site. Unlike the response to DSBs, Mre11 and recombination proteins are not recruited to hydroxyurea-stalled replication forks unless the forks collapse. The cellular response to DSBs and DNA replication stress is likely directed by the Mre11 complex detecting and processing DNA ends in conjunction with Sae2 and by RP-A recognizing single-stranded DNA and recruiting additional checkpoint and repair proteins.

  7. Photothermal therapy with immune-adjuvant nanoparticles together with checkpoint blockade for effective cancer immunotherapy

    Science.gov (United States)

    Chen, Qian; Xu, Ligeng; Liang, Chao; Wang, Chao; Peng, Rui; Liu, Zhuang

    2016-10-01

    A therapeutic strategy that can eliminate primary tumours, inhibit metastases, and prevent tumour relapses is developed herein by combining adjuvant nanoparticle-based photothermal therapy with checkpoint-blockade immunotherapy. Indocyanine green (ICG), a photothermal agent, and imiquimod (R837), a Toll-like-receptor-7 agonist, are co-encapsulated by poly(lactic-co-glycolic) acid (PLGA). The formed PLGA-ICG-R837 nanoparticles composed purely by three clinically approved components can be used for near-infrared laser-triggered photothermal ablation of primary tumours, generating tumour-associated antigens, which in the presence of R837-containing nanoparticles as the adjuvant can show vaccine-like functions. In combination with the checkpoint-blockade using anti-cytotoxic T-lymphocyte antigen-4 (CTLA4), the generated immunological responses will be able to attack remaining tumour cells in mice, useful in metastasis inhibition, and may potentially be applicable for various types of tumour models. Furthermore, such strategy offers a strong immunological memory effect, which can provide protection against tumour rechallenging post elimination of their initial tumours.

  8. The transcription factor E4F1 coordinates CHK1-dependent checkpoint and mitochondrial functions.

    Science.gov (United States)

    Rodier, Geneviève; Kirsh, Olivier; Baraibar, Martín; Houlès, Thibault; Lacroix, Matthieu; Delpech, Hélène; Hatchi, Elodie; Arnould, Stéphanie; Severac, Dany; Dubois, Emeric; Caramel, Julie; Julien, Eric; Friguet, Bertrand; Le Cam, Laurent; Sardet, Claude

    2015-04-14

    Recent data support the notion that a group of key transcriptional regulators involved in tumorigenesis, including MYC, p53, E2F1, and BMI1, share an intriguing capacity to simultaneously regulate metabolism and cell cycle. Here, we show that another factor, the multifunctional protein E4F1, directly controls genes involved in mitochondria functions and cell-cycle checkpoints, including Chek1, a major component of the DNA damage response. Coordination of these cellular functions by E4F1 appears essential for the survival of p53-deficient transformed cells. Acute inactivation of E4F1 in these cells results in CHK1-dependent checkpoint deficiency and multiple mitochondrial dysfunctions that lead to increased ROS production, energy stress, and inhibition of de novo pyrimidine synthesis. This deadly cocktail leads to the accumulation of uncompensated oxidative damage to proteins and extensive DNA damage, ending in cell death. This supports the rationale of therapeutic strategies simultaneously targeting mitochondria and CHK1 for selective killing of p53-deficient cancer cells.

  9. Tumor-suppressor genes, cell cycle regulatory checkpoints, and the skin

    Directory of Open Access Journals (Sweden)

    Ana Maria Abreu Velez

    2015-01-01

    Full Text Available The cell cycle (or cell-division cycle is a series of events that take place in a cell, leading to its division and duplication. Cell division requires cell cycle checkpoints (CPs that are used by the cell to both monitor and regulate the progress of the cell cycle. Tumor-suppressor genes (TSGs or antioncogenes are genes that protect the cell from a single event or multiple events leading to cancer. When these genes mutate, the cell can progress to a cancerous state. We aimed to perform a narrative review, based on evaluation of the manuscripts published in MEDLINE-indexed journals using the Medical Subject Headings (MeSH terms "tumor suppressor′s genes," "skin," and "cell cycle regulatory checkpoints." We aimed to review the current concepts regarding TSGs, CPs, and their association with selected cutaneous diseases. It is important to take into account that in some cell cycle disorders, multiple genetic abnormalities may occur simultaneously. These abnormalities may include intrachromosomal insertions, unbalanced division products, recombinations, reciprocal deletions, and/or duplication of the inserted segments or genes; thus, these presentations usually involve several genes. Due to their complexity, these disorders require specialized expertise for proper diagnosis, counseling, personal and family support, and genetic studies. Alterations in the TSGs or CP regulators may occur in many benign skin proliferative disorders, neoplastic processes, and genodermatoses.

  10. Checkpoint modulation--A new way to direct the immune system against renal cell carcinoma.

    Science.gov (United States)

    Bedke, Jens; Kruck, Stephan; Gakis, Georgios; Stenzl, Arnulf; Goebell, Peter J

    2015-01-01

    The introduction of targeted therapies like the tyrosine kinase (TKI) and mammalian target of rapamycin (mTOR) inhibitors has improved patients' survival in general. Nevertheless the prognosis remains limited. Therapies with a new mode of action are urgently warranted, especially those who would provoke long-term responders or long-lasting complete remissions as observed with unspecific immunotherapy with the cytokines interleukin-2 and interferon-α. In the recent years a deeper understanding of the underlying immunology of T cell activation led to the development of checkpoint inhibitors, which are mainly monocloncal antibodies and which enhances the presence of the co-stimulatory signals needed for T cell activation or priming. This review discusses the clinical data and ongoing studies available for the inhibition of the PD-1 (CD279) and CTLA-4 (CD152) axis in mRCC. In addition, potential future immunological targets are discussed. This approach of T-cell activation or re-activation by immunological checkpoint inhibition holds the inherent promise to directly affect the tumor cell and thereby to potentially cure a subset of patients with mRCC.

  11. DNA replication and spindle checkpoints cooperate during S phase to delay mitosis and preserve genome integrity.

    Science.gov (United States)

    Magiera, Maria M; Gueydon, Elisabeth; Schwob, Etienne

    2014-01-20

    Deoxyribonucleic acid (DNA) replication and chromosome segregation must occur in ordered sequence to maintain genome integrity during cell proliferation. Checkpoint mechanisms delay mitosis when DNA is damaged or upon replication stress, but little is known on the coupling of S and M phases in unperturbed conditions. To address this issue, we postponed replication onset in budding yeast so that DNA synthesis is still underway when cells should enter mitosis. This delayed mitotic entry and progression by transient activation of the S phase, G2/M, and spindle assembly checkpoints. Disabling both Mec1/ATR- and Mad2-dependent controls caused lethality in cells with deferred S phase, accompanied by Rad52 foci and chromosome missegregation. Thus, in contrast to acute replication stress that triggers a sustained Mec1/ATR response, multiple pathways cooperate to restrain mitosis transiently when replication forks progress unhindered. We suggest that these surveillance mechanisms arose when both S and M phases were coincidently set into motion by a unique ancestral cyclin-Cdk1 complex.

  12. Photothermal therapy with immune-adjuvant nanoparticles together with checkpoint blockade for effective cancer immunotherapy

    Science.gov (United States)

    Chen, Qian; Xu, Ligeng; Liang, Chao; Wang, Chao; Peng, Rui; Liu, Zhuang

    2016-01-01

    A therapeutic strategy that can eliminate primary tumours, inhibit metastases, and prevent tumour relapses is developed herein by combining adjuvant nanoparticle-based photothermal therapy with checkpoint-blockade immunotherapy. Indocyanine green (ICG), a photothermal agent, and imiquimod (R837), a Toll-like-receptor-7 agonist, are co-encapsulated by poly(lactic-co-glycolic) acid (PLGA). The formed PLGA-ICG-R837 nanoparticles composed purely by three clinically approved components can be used for near-infrared laser-triggered photothermal ablation of primary tumours, generating tumour-associated antigens, which in the presence of R837-containing nanoparticles as the adjuvant can show vaccine-like functions. In combination with the checkpoint-blockade using anti-cytotoxic T-lymphocyte antigen-4 (CTLA4), the generated immunological responses will be able to attack remaining tumour cells in mice, useful in metastasis inhibition, and may potentially be applicable for various types of tumour models. Furthermore, such strategy offers a strong immunological memory effect, which can provide protection against tumour rechallenging post elimination of their initial tumours. PMID:27767031

  13. Bounds on the dynamics of sink populations with noisy immigration

    DEFF Research Database (Denmark)

    Eager, Eric Alan; Guiver, Chris; Hodgson, Dave

    2014-01-01

    Sink populations are doomed to decline to extinction in the absence of immigration. The dynamics of sink populations are not easily modelled using the standard framework of per capita rates of immigration, because numbers of immigrants are determined by extrinsic sources (for example, source...... populations, or population managers). Here we appeal to a systems and control framework to place upper and lower bounds on both the transient and future dynamics of sink populations that are subject to noisy immigration. Immigration has a number of interpretations and can fit a wide variety of models found...

  14. Who is afraid of immigrants? Social predictors of fear of immigrants in Europe

    Directory of Open Access Journals (Sweden)

    Sebastian Năstuţă

    2011-12-01

    Full Text Available Starting from the assumption that „fear” or „the threat feeling” felt on immigrants as a group is a strong predictor of negative reaction and actions against these out-groups we are trying to identify in this paper the social predictors of these feelings. If most studies on anti-immigrant attitudes are oriented mainly to economic effects, city or municipality effects we included in our analysis not only the clasical variable like education, income, age, gender, professional status, citizenship as in previous studies, but also the religious affiliation and immigration descendence. Starting from EVS 2008 data we obtained results that confirms other studies and also we identified the positive strong effect of religious denomination on immigration threat feelings.

  15. Social Attitudes and Political Debate on Immigration: Spanish Perceptions of Romanian Immigrants

    Directory of Open Access Journals (Sweden)

    Simon McMAHON

    2011-05-01

    Full Text Available Prior to 2002 the Romanian population in Spain was negligible, yet today it constitutes the largest immigrant population, raising questions of how this country receives and integrates new migrant groups and negotiates perceptions of similarity and difference between natives and foreigners. Using survey data from the Centro de Investigaciones Científicas and political debates from the Congreso de los Diputados this paper asks how perceptions of Romanian immigrants develop over time. The paper finds that social perceptions of Romanian immigration and political debate on the Romanian population in Spain are somewhat disconnected, as social attitudes develop independently of elite-level political discourse. Therefore, just as immigrants are not perceived or presented in the same way in politics and society, or on a national and a local level, neither do the processes based on these perceptions, such as discrimination or exclusion, play out in the same way.

  16. Do Immigrants Make Us Safer? A Model on Crime, Immigration and the Labor Market

    OpenAIRE

    Thomas Bassetti; Luca Corazzini; Darwin Cortes; Luca Nunziata

    2013-01-01

    We present a two-country equilibrium model with search costs in which the structural characteristics of the labor market in each economy affects the relationship between immigration and crime. The main result of the model is that countries with ?flexible labor markets are likely to see a negative relationship between immigration and crime. By combining data from the European Social Survey with the OECD Employment Protection Index, we find supporting evidence in favor of this theoretical predi...

  17. Early Academic Achievement Among American Low-Income Black Students from Immigrant and Non-Immigrant Families.

    Science.gov (United States)

    Calzada, Esther; Barajas-Gonzalez, R Gabriela; Dawson-McClure, Spring; Huang, Keng-Yen; Palamar, Joseph; Kamboukos, Dimitra; Brotman, Laurie Miller

    2015-11-01

    At least half of the well-documented achievement gap for low-income Black children is already present in kindergarten, due in part to limited opportunities for acquiring foundational skills necessary for school success. There is some evidence that low-income minority children from immigrant families have more positive outcomes than their non-immigrant counterparts, although little is known about how the immigrant paradox may manifest in young children. This study examines foundational school readiness skills (academic and social-emotional learning) at entry into pre-kindergarten (pre-k) and achievement in kindergarten and second grade among Black children from low-income immigrant and non-immigrant families (N = 299). Immigrant and non-immigrant children entered pre-k with comparable readiness scores; in both groups, reading scores decreased significantly from kindergarten to second grade and math scores decreased significantly for non-immigrant children and marginally for immigrant children. Regardless of immigrant status, pre-k school readiness and pre-k classroom quality were associated with elementary school achievement. However, declines in achievement scores were not as steep for immigrant children and several predictive associations were moderated by immigrant status, such that among those with lower pre-k school readiness or in lower quality classrooms, immigrant children had higher achievement test scores than children from non-immigrant families. Findings suggest that immigrant status provides young Black students with some protection against individual- and classroom-level risk factors for early underachievement in elementary school.

  18. Impact of immigration on health and human services: Florida's experience.

    Science.gov (United States)

    McNeece, C Aaron; Falconer, Mary Kay; Springer, David

    2002-01-01

    Florida has been the destination for large numbers of immigrants fleeing political persecution or economic hardships. Cubans and Haitians have been two of the largest immigrant groups arriving and settling in Florida. Both have received national and local attention. This article describes the immigration experience of Haitians and Cubans in Florida. The descriptions emphasize the differences between these two groups in their adjustment to life in south Florida. The article also addresses Florida's reaction to federal policies regarding immigration and highlights Florida's struggle to meet the service needs of these immigrant populations. Fiscal impacts of immigration are quantified in several service categories, including education, social services, health care, and criminal justice. Florida's action based on the documentation of the immigration fiscal impact is explained. Finally, how the state allocated the $18 million in federal funding provided as a response to Florida's documented impact is covered.

  19. Transition to Motherhood as an Immigrant: Risks and Obstacles

    Directory of Open Access Journals (Sweden)

    Ruveyde Aydin

    2017-09-01

    Full Text Available The process of transition to motherhood that brings along a number of vital changes may be full of risks and difficulties for immigrant mothers. Poverty, being unfamiliar with the language of the country that the mother migrated, inability of healthcare policies in covering healthcare expenses of immigrants, insufficiency of social assistance and loneliness may negatively affect health of mother and infant. Postpartum immigrant mothers are seen depression, anxiety, stress and social isolation because of these obstacles. Therefore, health care professionals, who provide care to immigrant mothers, should clarify immigrant mothers' religious, cultural beliefs and attitudes. Procurement of peer support is important by developing care programs special to immigrant mothers and ensuring immigrant women to come together. Increase in the number of translators in hospitals and prepara-tion of education materials in native language of mothers will improve the level of benefiting from healthcare services. [Psikiyatride Guncel Yaklasimlar - Current Approaches in Psychiatry 2017; 9(3.000: 250-262

  20. Evaluating the Impact of Immigration Policies on Health Status Among Undocumented Immigrants: A Systematic Review

    Science.gov (United States)

    Martinez, Omar; Wu, Elwin; Sandfort, Theo; Dodge, Brian; Carballo-Dieguez, Alex; Pinto, Rogeiro; Rhodes, Scott D.; Moya, Eva; Chavez-Baray, Silvia

    2014-01-01

    Over the past two decades, new anti-immigration policies and laws have emerged to address the migration of undocumented immigrants. A systematic review of the literature was conducted to assess and understand how these immigration policies and laws may affect both access to health services and health outcomes among undocumented immigrants. Eight databases were used to conduct this review, which returned 325 papers that were assessed for validity based on specified inclusion criteria. Forty critically appraised articles were selected for analysis; thirty articles related to access to health services, and ten related to health outcomes. The articles showed a direct relationship between anti-immigration policies and their effects on access to health services. In addition, as a result of these policies, undocumented immigrants were impacted by mental health outcomes, including depression, anxiety, and post-traumatic stress disorder. Action items were presented, including the promotion of cultural diversity training and the development of innovative strategies to support safety-net health care facilities serving vulnerable populations. PMID:24375382

  1. Evaluating the impact of immigration policies on health status among undocumented immigrants: a systematic review.

    Science.gov (United States)

    Martinez, Omar; Wu, Elwin; Sandfort, Theo; Dodge, Brian; Carballo-Dieguez, Alex; Pinto, Rogeiro; Rhodes, Scott D; Rhodes, Scott; Moya, Eva; Chavez-Baray, Silvia

    2015-06-01

    Over the past two decades, new anti-immigration policies and laws have emerged to address the migration of undocumented immigrants. A systematic review of the literature was conducted to assess and understand how these immigration policies and laws may affect both access to health services and health outcomes among undocumented immigrants. Eight databases were used to conduct this review, which returned 325 papers that were assessed for validity based on specified inclusion criteria. Forty critically appraised articles were selected for analysis; thirty articles related to access to health services, and ten related to health outcomes. The articles showed a direct relationship between anti-immigration policies and their effects on access to health services. In addition, as a result of these policies, undocumented immigrants were impacted by mental health outcomes, including depression, anxiety, and post-traumatic stress disorder. Action items were presented, including the promotion of cultural diversity training and the development of innovative strategies to support safety-net health care facilities serving vulnerable populations.

  2. Language and the Earnings of Immigrants.

    Science.gov (United States)

    Dustmann, Christian; van Soest, Arthur

    2002-01-01

    Analysis of panel data on immigrants to Germany 1984-94 focused on the relationship of language proficiency and productivity. Results show how time-varying measurement errors can lead to downward bias on the effect of fluency on earnings. Language proficiency is thus far more important than studies have suggested. (Contains 30 references.) (SK)

  3. Acculturation of Developmental Timetables among Adolescent Immigrants.

    Science.gov (United States)

    Schmitt-Rodermund, Eva; Silbereisen, Rainer K.

    The acculturation of developmental timetables for autonomy from parental supervision and in social relationships was studied in a sample of 220 ethnic German immigrants to Germany from Romania, Poland, and countries of the former Soviet Union. The acculturation rate was predicted to be related to prior differences in parent-adolescent interaction…

  4. K-12 Educational Outcomes of Immigrant Youth

    Science.gov (United States)

    Crosnoe, Robert; Turley, Ruth N. Lopez

    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 Lopez Turley summarize these K-12 patterns, paying special attention to differences in academic functioning across…

  5. Cultural Challenges Faced by Mexican Immigrant Students

    Science.gov (United States)

    Zugel, Kevin

    2012-01-01

    This purpose of this investigation is to explore the cultural challenges faced by Mexican immigrant students through the study of current literature. Four themes emerged as a result of the investigation: dominant pedagogy, educational skills, deficit model, and student identities. The themes are discussed and suggestions are made as to how these…

  6. Immigration and the evolution of economic theory.

    Science.gov (United States)

    Passaris, C

    1989-12-01

    This is a review of "the limited and scant contributions made to immigration theory in the context of the evolution of economic thought over a protracted historical time span." The economic theories considered include those of the mercantilists, Adam Smith, the classical economists, and J. M. Keynes. (SUMMARY IN FRE AND SPA)

  7. Branching Processes with Immigration and Related Topics

    Institute of Scientific and Technical Information of China (English)

    LI Zeng-hu

    2006-01-01

    This is a survey on the recent progresses in the study of branching processes with immigration,generalized Ornstein-Uhlenbeck processes,and affine Markov processes.We mainly focus on the applications of skew convolution semigroups and the connections in those processes.

  8. Identity Reconfiguration of Immigrants in Portugal

    Directory of Open Access Journals (Sweden)

    Ricardo Vieira

    2010-07-01

    Full Text Available The starting point is the principle that there is no immigrant culture, but rather, different ways of living, coexisting and identifying oneself within the cultural worlds that each subject crosses on his or her social path. Here we study Brazilian immigrants in Portugal, working with the first wave (starting at the end of the 1980s and the second wave (at the turn of the 20th to 21st century. We intend, firstly, to show how identity is reconstructed between two banks: the departure culture and the arrival culture. Secondly, we intend to give a voice to the most silent in the understanding of immigrants: the process of identity reconstruction of Brazilian immigrants is presented, resulting from ethno-biographic interviews. We will consider the cultural transfusion theory and observe the heterogeneous ways of living between cultures, whether by rejecting the departure culture (the Oblato‘s case, refusing the arrival one at a given moment (the mono-cultural subject according to the source culture, living in an ambivalent manner between the two (the multicultural self, or, finally, inventing a third bank, as the poets say, which corresponds to an attitude of including the cultural differences through which one crosses during his or her life history in an intercultural self (the Intercultural Transfuga.

  9. Coping with Illegal Immigrants in School

    Science.gov (United States)

    Hardy, Lawrence

    2007-01-01

    Superintendent Steve Joel had reason to be concerned when he got a call from the police chief telling him that federal immigration authorities were coming to the local Swift & Company meat-packing plant to round up undocumented workers as part of a six-state raid. Of the 8,000 students in the Grand Island School District in Central Nebraska,…

  10. No shortcuts: selective immigration and integration

    NARCIS (Netherlands)

    J. Doomernik; R. Koslowski; J. Laurence; R. Maxwell; I. Michalowski; D. Thränhardt

    2009-01-01

    This paper examines the selective migration policies and assumptions about immigrant integration. Many arguments for selecting migrants on the basis of skills and education, particularly in Europe, have assumed that highly-skilled migrants can be easily integrated, whereas migrants with low skills n

  11. Poverty and Program Participation among Immigrant Children

    Science.gov (United States)

    Borjas, George J.

    2011-01-01

    Researchers have long known that poverty in childhood is linked with a range of negative adult socioeconomic outcomes, from lower educational achievement and behavioral problems to lower earnings in the labor market. But few researchers have explored whether exposure to a disadvantaged background affects immigrant children and native children…

  12. Immigration, parasitic infection, and United States religiosity.

    Science.gov (United States)

    Wall, Jaimie N; Shackelford, Todd K

    2012-04-01

    Fincher & Thornhill (F&T) present a powerful case for the relationship between parasite-stress and religiosity. We argue, however, that the United States may be more religious than can be accounted for by parasite-stress. This greater religiosity might be attributable to greater sensitivity to immigration, which may hyperactivate evolved mechanisms that motivate avoidance of potential carriers of novel parasites.

  13. INTEGRATION POLICY TOWARDS IMMIGRANTS: CURRENT EXPERIENCE

    Directory of Open Access Journals (Sweden)

    Nadiia Bureiko

    2012-03-01

    Full Text Available In the contemporary world the intensity of the immigration movements is constantly increasing. Countries which experience great immigrant flows are facing numerous problems which should be solved. The article studies the current immigration flows in EU countries, the United States of America and Canada and presents three main models of integration policy towards immigrants – political assimilation, functional integration and multicultural model. Separate models are distinguished for the Muslims’ integration. The author examines the peculiarities of every model and examines the conclusions provided by the Migrant Integration Policy Index (MIPEX concerning the situation of the immigrants’ integration in 31 countries in 2011. Among all the policy indicators the first that are defined are as follows: political participation, education, labour market mobility and anti-discrimination. The situation with immigrants’ integration in Ukraine is also studied as it is gaining a great attention of the authorities and the public. The measures and practical steps done regarding this situation in Ukraine in recent years are analyzed using the information offered by the State Migration Service of Ukraine.

  14. Northern Horizons: Latinas in the New Immigration.

    Science.gov (United States)

    Sanchez-Korrol, Virginia

    Many Latin American immigrants have encountered new social problems, including language barriers, stereotypes associated with being hispanic, special insecurities experienced by women, role changes, isolation, and alienation from families. Attitudes about return migration appear to be different in men and women. Men more often wish to return to…

  15. Teacher Voices: Immigration, Language and Culture

    Science.gov (United States)

    National Writing Project (NJ1), 2011

    2011-01-01

    This report presents stories of six teachers who believe in the power and promise of immigrant students and English language learners. Their stories begin to help readers understand the assets these groups of students bring to classrooms, the challenges they--both students and teachers--face, and the role that teachers and schools play in their…

  16. Educating Immigrant Students in Urban Districts

    Science.gov (United States)

    Nur, Shurki; Hunter, Richard C.

    2009-01-01

    Immigrant children constitute the fastest-growing population in the United States, and their presence is rapidly changing the demographics of American public schools--especially in cities where they typically settle with their families. Because these students' languages, cultures, and values differ from those of educators--and indeed from one…

  17. Examining Entrepreneurial Motivations of Indian Immigrants

    Science.gov (United States)

    Bajaj, Nitin

    2014-01-01

    To what extent does the success of an entrepreneurial venture in the United States depend upon an immigrant entrepreneur's individual traits such as motivation, need for achievement, perception of exogenous business factors, and relationship networking? The findings from the study present significant differences in motivation and need for…

  18. Transmission of zoonoses through immigration and tourism

    Directory of Open Access Journals (Sweden)

    Nikoletta Mavroidi

    2008-12-01

    Full Text Available More than 200 of the documented zoonoses represent a high proportion of the infectious diseases that cause cases of morbidity and mortality and almost 75% are emerging infections. Immigration and tourism are human activities that are included in the broader field of human migration and travel. Travel plays a significant role in the emergence and spread of disease. The migration of humans has provided the route of spread for infectious diseases and zoonoses (for example, plague, yellow fever, monkey pox and severe acute respiratory syndrome. Tourism constitutes a small fraction of overall movements of humans but a point worthy of note is the number of international travellers has increased by more than 1 300% over the last 50 years. In addition, over 80 million people, mostly from developing countries, are legal or illegal immigrants. The consequences of travel extend beyond the traveller to the population visited and the ecosystem. Tourism and immigration may constitute an interface for mixing different genetic and ecological profiles, as well as cultural and social aspects, which is of particular interest in regard to zoonoses. Primary prevention, epidemiological surveillance and health education in the framework of intersectoral and international collaboration remain the cornerstone for response to and control of zoonoses in the context of tourism and immigration.

  19. Contacts of general practitioners with illegal immigrants.

    NARCIS (Netherlands)

    Reijneveld, S.; Verheij, R.; Herten, L. van; Bakker, D. de

    2001-01-01

    Aims: Violence and economic hardship cause many people to industrialized countries, often without obtaining an residence permit. The aim of this study is to gain insight into the factors that determine the occurrence of contacts in primary health care with such illegal immigrants. Methods: Data were

  20. Financial capability, asset ownership, and later-age immigration: evidence from a sample of low-income older Asian immigrants.

    Science.gov (United States)

    Nam, Yunju; Lee, Eun Jeong; Huang, Jin; Kim, Junpyo

    2015-01-01

    We examined financial capability and asset ownership among low-income older Asian immigrants with special attention given to later-age immigrants who came to the United States when they were 55 years old or older. Survey data collected from supported employment program participants (N = 150) were used. The analyses demonstrated a low level of financial knowledge and asset ownership in the sample. The findings also indicated that later-age immigrants' financial-management skills, knowledge of social programs, and asset ownership were significantly lower than those of young-age immigrants. These findings call for active interventions to enhance economic security among low-income older Asian immigrants.