3,060 research outputs found

    Targeted next-generation sequencing of plasma DNA from cancer patients: factors influencing consistency with tumour DNA and prospective investigation of its utility for diagnosis

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    Use of circulating tumour DNA (ctDNA) as a liquid biopsy has been proposed for potential identification and monitoring of solid tumours. We investigate a next-generation sequencing approach for mutation detection in ctDNA in two related studies using a targeted panel. The first study was retrospective, using blood samples taken from melanoma patients at diverse timepoints before or after treatment, aiming to evaluate correlation between mutations identified in biopsy and ctDNA, and to acquire a first impression of influencing factors. We found good concordance between ctDNA and tumour mutations of melanoma patients when blood samples were collected within one year of biopsy or before treatment. In contrast, when ctDNA was sequenced after targeted treatment in melanoma, mutations were no longer found in 9 out of 10 patients, suggesting the method might be useful for detecting treatment response. Building on these findings, we focused the second study on ctDNA obtained before biopsy in lung patients, i.e. when a tentative diagnosis of lung cancer had been made, but no treatment had started. The main objective of this prospective study was to evaluate use of ctDNA in diagnosis, investigating the concordance of biopsy and ctDNA-derived mutation detection. Here we also found positive correlation between diagnostic lung biopsy results and pre-biopsy ctDNA sequencing, providing support for using ctDNA as a cost-effective, non-invasive solution when the tumour is inaccessible or when biopsy poses significant risk to the patient

    Perancangan Sistem Informasi Pengelola Barang/Inventaris Di Jc Komp

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    Inventory information system is a system used to enter inventory data into the database, so that there are no errors in input, output data, and reporting based on the desired data. based on surveys and interviews with jc comp personnel, information was obtained that the existing system in the jc comp warehouse section is still manual. therefore, the system that will be created by the author is the result of a replication of the existing system in the jc comp warehouse section. in addition to the process of input and output of goods, this information system is also equipped with features for creating data reports, input and output of goods, and searching for goods data by item name. with the inventory information system is expected to be useful for the warehouse parts jc comp. By implementing this system in the jc comp warehouse, it is hoped that it can reduce errors that may occur. this system is also expected to further speed up the process of input, output, and report generation, which in turn will help the jc comp warehouseSistem Informasi Persediaan Barang adalah sebuah sistem yang digunakan untuk memasukkan data-data persediaan barang ke dalam database, sehinggga tidak terjadi kesalahan dalam input, output data, dan pembuatan laporan berdasarkan data yang diinginkan. Berdasarkan survey dan wawancara dengan bagian personalia Jc Komp, didapatkan informasi bahwa sistem yang ada dibagian gudang Jc Komp masih manual. Oleh karena itu, sistem yang akan dibuat oleh penulis adalah hasil replikasi dari sistem yang telah ada dibagian gudang Jc Comp. Selain proses input dan output barang, pada sistem informasi ini juga dilengkapi fitur pembuatan laporan data, input, dan output barang, dan pencarian data barang berdasarkan nama barang. Dengan adanya Sistem Informasi persediaan barang ini diharapkan dapat bermanfaat bagi bagian gudang Jc Komp. Dengan diterapkannya sistem ini pada bagian gudang Jc Comp, maka diharapkan dapat mengurangi kesalahan-kesalahan yang mungkin terjadi. Sistem ini juga diharapkan dapat lebih mempercepat proses input, output, dan pembuatan laporan yang pada akhirnya dapat membantu bagian gudang Jc Komp

    Amenable L-2-Theoretic Methods and Knot Concordance

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    We reveal new structures in the topological knot concordance group. As a key ingredient, we develop obstructions using L-2-theoretic methods for amenable groups in Strebel's class recently introduced by Orr and the author. Concerning (h)-solvable knots, which are defined in terms of certain Whitney towers of height h in bounding 4-manifolds, we show the following: for any n>1, there are (n)-solvable but non-(n. 5)-solvable (and therefore nonslice) knots, which are not detected by prior methods using Cochran-Orr-Teichner L-2-signature obstructions as well as Levine algebraic obstructions and Casson-Gordon invariants.X1197sciescopu

    Dynamics of Network Formation Processes in the Co-Author Model

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    This article studies the dynamics in the formation processes of a mutual consent network in game theory setting: the Co-Author Model. In this article, a limited observation is applied and analytical results are derived. Then, 2 parameters are varied: the number of individuals in the network and the initial probability of the links in the network in its initial state. A simulation result shows a finding that is consistent with an analytical result for a state of equilibrium while it also shows different possible equilibria.Dynamics, Network, Game Theory, Model,Simulation, Equilibrium, Complexity

    High-level polyomavirus JC viruria following long-term steroid therapy

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    CASE REPORT JC virus is a highly seroprevalent ubiquitous polyomavirus which is acquired at an early age through respiratory or oral route, Thereafter JCV establishes persistent, but mainly asymptomatic, infections in various tissues, including the genitourinary tract and brain Corresponding author Cristina Costa, MD S.C.D.U. Virologia Azienda Ospedaliero-Universitaria San Giovanni Battista di Torino Via Santena, 9 -10126 Torino E-mail: [email protected] increasing with age, with adult prevalence rate often between 15% and 60

    Engineering Framework to Utilize Miniaturized Charpy Type SE(B) Specimens to Predict Jc of Full Sized Specimens

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    AbstractThis paper introduces our experience of using miniature Charpy type SE(B) specimen in obtaining fracture toughness Jc of a material in the ductile to brittle transition temperature (DBTT) region. Width W x thickness B of 2 x 2 mm, 3 x 3 mm and 10 x 10 mm were chosen as miniature specimens and 25 x 25 mm were chosen as full sized specimen. 0.55% carbon steel JIS S55C, whose tensile to yield stress ratio σTS/σYS was equal to 1.8 was chosen as a material to simulate a degraded (embrittled) material in the DBTT region. Focus was placed on whether cleavage fracture could be predicted for these miniaturized specimens. Another focus was placed on whether the Jc of full sized specimen is predictable from the test results of the miniature sized specimens, in case cleavage fracture were observed. The results showed that the modified Ritch-Knott-Rice (RKR) failure criterion (which predicts the onset of cleavage fracture when the crack opening stress measured at 4 times the crack-tip opening displacement exceeds this σ22c) could predict whether cleavage fracture would occur or not. Another finding was that, in case cleavage fracture was observed though, the critical value σ22c in the modified RKR failure criterion was independent of specimen size, and thus, Jc of the full sized specimen is predictable from the miniature specimen test results, though M = (W-a)σYS/Jc was smaller than ASTM E1921 requirement of 30. Here, a and σYS are crack length and yield strength, respectively

    Shifting attention in viewer- and object-based reference frames after unilateral brain injury

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    The aims of the present study were to investigate the respective roles that object- and viewer-based reference frames play in reorienting visual attention, and to assess their influence after unilateral brain injury. To do so, we studied 16 right hemisphere injured (RHI) and 13 left hemisphere injured (LHI) patients. We used a cueing design that manipulates the location of cues and targets relative to a display comprised of two rectangles (i.e., objects). Unlike previous studies with patients, we presented all cues at midline rather than in the left or right visual fields. Thus, in the critical conditions in which targets were presented laterally, reorienting of attention was always from a midline cue. Performance was measured for lateralized target detection as a function of viewer-based (contra- and ipsilesional sides) and object-based (requiring reorienting within or between objects) reference frames. As expected, contralesional detection was slower than ipsilesional detection for the patients. More importantly, objects influenced target detection differently in the contralesional and ipsilesional fields. Contralesionally, reorienting to a target within the cued object took longer than reorienting to a target in the same location but in the uncued object. This finding is consistent with object-based neglect. Ipsilesionally, the means were in the opposite direction. Furthermore, no significant difference was found in object-based influences between the patient groups (RHI vs. LHI). These findings are discussed in the context of reference frames used in reorienting attention for target detection

    Craspase Orthologs Cleave a Nonconserved Site in Target Protein Csx30

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    The Craspase CRISPR-Cas effector consists of the RNA-guided ribonuclease gRAMP and the protease TPR-CHAT, coupling target RNA recognition to protease activation. The natural substrate of Craspase is Csx30, a protein cleaved in two fragments that subsequently activates downstream antiviral pathways. Here, we determined the protease substrate specificity of Craspase from Candidatus “Jettenia caeni” (Jc-Craspase). We find that Jc-Craspase cleaves Jc-Csx30 in a target RNA-dependent fashion in A|S, which is different from the sites found in two other studied Craspases (L|D and M|K for Candidatus “Scalindua brodae” and Desulfonema ishimotonii, respectively). The fact that Craspase cleaves a nonconserved site across orthologs indicates the evolution of specific protein interactions between Craspase and its respective Csx30 target protein. The Craspase family thus represents a panel of proteases with different substrate specificities, which we exploited for the development of a readout for multiplexed RNA detection.BN/Stan Brouns LabBT/Environmental Biotechnolog

    The role of Plasmodium falciparum var genes in malaria in pregnancy

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    Sequestration of Plasmodium falciparum-infected erythrocytes in the placenta is responsible for many of the harmful effects of malaria during pregnancy. Sequestration occurs as a result of parasite adhesion molecules expressed on the surface of infected erythrocytes binding to host receptors in the placenta such as chondroitin sulphate A (CSA). Identification of the parasite ligand(s) responsible for placental adhesion could lead to the development of a vaccine to induce antibodies to prevent placental sequestration. Such a vaccine would reduce the maternal anaemia and infant deaths that are associated with malaria in pregnancy. Current research indicates that the parasite ligands mediating placental adhesion may be members of the P. falciparum variant surface antigen family PfEMP1, encoded by var genes. Two relatively well-conserved subfamilies of var genes have been implicated in placental adhesion, however, their role remains controversial. This review examines the evidence for and against the involvement of var genes in placental adhesion, and considers whether the most appropriate vaccine candidates have yet been identified

    Viroporin activity of the JC polyomavirus is regulated by interactions with the adaptor protein complex 3

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    Viroporins, which are encoded by a wide range of animal viruses, oligomerize in host cell membranes and form hydrophilic pores that can disrupt a number of physiological properties of the cell. Little is known about the relationship between host cell proteins and viroporin activity. The human JC polyomavirus (JCV) is the causative agent of progressive multifocal leukoencephalopathy. The JCV-encoded agnoprotein, which is essential for viral replication, has been shown to act as a viroporin. Here we demonstrate that the JCV agnoprotein specifically interacts with adaptor protein complex 3 through its delta subunit. This interaction interrupts adaptor protein complex 3-mediated vesicular trafficking with suppression of the targeting of the protein to the lysosomal degradation pathway and instead permits the transport of agnoprotein to the cell surface with resulting membrane permeabilization. The findings demonstrate a previously undescribed paradigm in virus-host interactions allowing the host to regulate viroporin activity and suggest that the viroporins of other viruses may also be highly regulated by specific interactions with host cell proteins
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