7,865 research outputs found
Characterization of human mesothelin transcripts in ovarian and pancreatic cancer
BACKGROUND: Mesothelin is an attractive target for cancer immunotherapy due to its restricted expression in normal tissues and high level expression in several tumor types including ovarian and pancreatic adenocarcinomas. Three mesothelin transcript variants have been reported, but their relative expression in normal tissues and tumors has been poorly characterized. The goal of the present study was to clarify which mesothelin transcript variants are commonly expressed in human tumors. METHODS: Human genomic and EST nucleotide sequences in the public databases were used to evaluate sequences reported for the three mesothelin transcript variants in silico. Subsequently, RNA samples from normal ovary, ovarian and pancreatic carcinoma cell lines, and primary ovarian tumors were analyzed by reverse transcription-polymerase chain reaction (RT-PCR) and nucleotide sequencing to directly identify expressed transcripts. RESULTS: In silico comparisons of genomic DNA sequences with available EST sequences supported expression of mesothelin transcript variants 1 and 3, but there were no sequence matches for transcript variant 2. Newly-derived nucleotide sequences of RT-PCR products from tissues and cell lines corresponded to mesothelin transcript variant 1. Mesothelin transcript variant 2 was not detected. Transcript variant 3 was observed as a small percentage of total mesothelin amplification products from all studied cell lines and tissues. Fractionation of nuclear and cytoplasmic RNA indicated that variant 3 was present primarily in the nuclear fraction. Thus, mesothelin transcript variant 3 may represent incompletely processed hnRNA. CONCLUSION: Mesothelin transcript variant 1 represents the predominant mature mRNA species expressed by both normal and tumor cells. This conclusion should be important for future development of cancer immunotherapies, diagnostic tests, and gene microarray studies targeting mesothelin
Overcoming cross-cultural group work tensions: mixed student perspectives on the role of social relationships
As universities worldwide rapidly internationalise, higher education classrooms have become unique spaces for collaboration between students from different countries. One common way to encourage collaboration between diverse peers is through group work. However, previous research has highlighted that cross-cultural group work can be challenging and has hinted at potential social tensions. To understand this notion better, we have used robust quantitative tools in this study to select 20 participants from a larger classroom of 860 students to take part in an in-depth qualitative interview about cross-cultural group work experiences. Participant views on social tensions in cross-cultural group work were elicited using a unique mediating artefact method to encourage reflection and in-depth discussion. In our analysis of emergent interview themes, we compared student perspectives on the role of social relationships in group work by their academic performance level. Our findings indicated that all students interviewed desired the opportunity to form social relationships with their group work members, but their motivations for doing so varied widely by academic performance level
Theoretical Constraints on the Higgs Effective Couplings
We derive constraints on the sign of couplings in an effective Higgs
Lagrangian using prime principles such as the naturalness principle, global
symmetries, and unitarity. Specifically, we study four dimension-six operators,
O_H, O_y, O_g, and O_gamma, which contribute to the production and decay of the
Higgs boson at the Large Hadron Collider (LHC), among other things. Assuming
the Higgs is a fundamental scalar, we find: 1) the coefficient of O_H is
positive except when there are triplet scalars, resulting in a reduction in the
Higgs on-shell coupling from their standard model (SM) expectations if no other
operators contribute, 2) the linear combination of O_H and O_y controlling the
overall Higgs coupling to fermion is always reduced, 3) the sign of O_g induced
by a new colored fermion is such that it interferes destructively with the SM
top contribution in the gluon fusion production of the Higgs, if the new
fermion cancels the top quadratic divergence in the Higgs mass, and 4) the
correlation between naturalness and the sign of O_gamma is similar to that of
O_g, when there is a new set of heavy electroweak gauge bosons. Next
considering a composite scalar for the Higgs, we find the reduction in the
on-shell Higgs couplings persists. If further assuming a collective breaking
mechanism as in little Higgs theories, the coefficient of O_H remains positive
even in the presence of triplet scalars. In the end, we conclude that the gluon
fusion production of the Higgs boson is reduced from the SM rate in all
composite Higgs models. Our study suggests a wealth of information could be
revealed by precise measurements of the Higgs couplings, providing strong
motivations for both improving on measurements at the LHC and building a
precision machine such as the linear collider.Comment: 37 pages, one figure; v2: improved discussion on dispersion relation
and other minor modifications; version accepted for publication
Does shear wave ultrasound independently predict axillary lymph node metastasis in women with invasive breast cancer?
Shear wave elastography (SWE) shows promise as an adjunct to greyscale ultrasound examination in assessing breast masses. In breast cancer, higher lesion stiffness on SWE has been shown to be associated with features of poor prognosis. The purpose of this study was to assess whether lesion stiffness at SWE is an independent predictor of lymph node involvement. Patients with invasive breast cancer treated by primary surgery, who had undergone SWE examination were eligible. Data were retrospectively analysed from 396 consecutive patients. The mean stiffness values were obtained using the Aixplorer(®) ultrasound machine from SuperSonic Imagine Ltd. Measurements were taken from a region of interest positioned over the stiffest part of the abnormality. The average of the mean stiffness value obtained from each of two orthogonal image planes was used for analysis. Associations between lymph node involvement and mean lesion stiffness, invasive cancer size, histologic grade, tumour type, ER expression, HER-2 status and vascular invasion were assessed using univariate and multivariate logistic regression. At univariate analysis, invasive size, histologic grade, HER-2 status, vascular invasion, tumour type and mean stiffness were significantly associated with nodal involvement. Nodal involvement rates ranged from 7 % for tumours with mean stiffness <50 kPa to 41 % for tumours with a mean stiffness of >150 kPa. At multivariate analysis, invasive size, tumour type, vascular invasion, and mean stiffness maintained independent significance. Mean stiffness at SWE is an independent predictor of lymph node metastasis and thus can confer prognostic information additional to that provided by conventional preoperative tumour assessment and staging
Mitochondrial and nuclear genes suggest that stony corals are monophyletic but most families of stony corals are not (Order Scleractinia, Class Anthozoa, Phylum Cnidaria)
Modern hard corals (Class Hexacorallia; Order Scleractinia) are widely studied because of their fundamental role in reef
building and their superb fossil record extending back to the Triassic. Nevertheless, interpretations of their evolutionary
relationships have been in flux for over a decade. Recent analyses undermine the legitimacy of traditional suborders,
families and genera, and suggest that a non-skeletal sister clade (Order Corallimorpharia) might be imbedded within the
stony corals. However, these studies either sampled a relatively limited array of taxa or assembled trees from heterogeneous
data sets. Here we provide a more comprehensive analysis of Scleractinia (127 species, 75 genera, 17 families) and various
outgroups, based on two mitochondrial genes (cytochrome oxidase I, cytochrome b), with analyses of nuclear genes (ßtubulin,
ribosomal DNA) of a subset of taxa to test unexpected relationships. Eleven of 16 families were found to be
polyphyletic. Strikingly, over one third of all families as conventionally defined contain representatives from the highly
divergent "robust" and "complex" clades. However, the recent suggestion that corallimorpharians are true corals that have
lost their skeletons was not upheld. Relationships were supported not only by mitochondrial and nuclear genes, but also
often by morphological characters which had been ignored or never noted previously. The concordance of molecular
characters and more carefully examined morphological characters suggests a future of greater taxonomic stability, as well as
the potential to trace the evolutionary history of this ecologically important group using fossils
What we talk about when we talk about "global mindset": managerial cognition in multinational corporations
Recent developments in the global economy and in multinational corporations have placed significant emphasis on the cognitive orientations of managers, giving rise to a number of concepts such as “global mindset” that are presumed to be associated with the effective management of multinational corporations (MNCs). This paper reviews the literature on global mindset and clarifies some of the conceptual confusion surrounding the construct. We identify common themes across writers, suggesting that the majority of studies fall into one of three research perspectives: cultural, strategic, and multidimensional. We also identify two constructs from the social sciences that underlie the perspectives found in the literature: cosmopolitanism and cognitive complexity and use these two constructs to develop an integrative theoretical framework of global mindset. We then provide a critical assessment of the field of global mindset and suggest directions for future theoretical and empirical research
A transcriptomic snapshot of early molecular communication between Pasteuria penetrans and Meloidogyne incognita
© The Author(s). 2018Background: Southern root-knot nematode Meloidogyne incognita (Kofoid and White, 1919), Chitwood, 1949 is a key pest of agricultural crops. Pasteuria penetrans is a hyperparasitic bacterium capable of suppressing the nematode reproduction, and represents a typical coevolved pathogen-hyperparasite system. Attachment of Pasteuria endospores to the cuticle of second-stage nematode juveniles is the first and pivotal step in the bacterial infection. RNA-Seq was used to understand the early transcriptional response of the root-knot nematode at 8 h post Pasteuria endospore attachment. Results: A total of 52,485 transcripts were assembled from the high quality (HQ) reads, out of which 582 transcripts were found differentially expressed in the Pasteuria endospore encumbered J2 s, of which 229 were up-regulated and 353 were down-regulated. Pasteuria infection caused a suppression of the protein synthesis machinery of the nematode. Several of the differentially expressed transcripts were putatively involved in nematode innate immunity, signaling, stress responses, endospore attachment process and post-attachment behavioral modification of the juveniles. The expression profiles of fifteen selected transcripts were validated to be true by the qRT PCR. RNAi based silencing of transcripts coding for fructose bisphosphate aldolase and glucosyl transferase caused a reduction in endospore attachment as compared to the controls, whereas, silencing of aspartic protease and ubiquitin coding transcripts resulted in higher incidence of endospore attachment on the nematode cuticle. Conclusions: Here we provide evidence of an early transcriptional response by the nematode upon infection by Pasteuria prior to root invasion. We found that adhesion of Pasteuria endospores to the cuticle induced a down-regulated protein response in the nematode. In addition, we show that fructose bisphosphate aldolase, glucosyl transferase, aspartic protease and ubiquitin coding transcripts are involved in modulating the endospore attachment on the nematode cuticle. Our results add new and significant information to the existing knowledge on early molecular interaction between M. incognita and P. penetrans.Peer reviewedFinal Published versio
Testing the theory of immune selection in cancers that break the rules of transplantation
Modification of cancer cells likely to reduce their immunogenicity, including loss or down-regulation of MHC molecules, is now well documented and has become the main support for the concept of immune surveillance. The evidence that these modifications, in fact, result from selection by the immune system is less clear, since the possibility that they may result from reorganized metabolism associated with proliferation or from cell de-differentiation remains. Here, we (a) survey old and new transplantation experiments that test the possibility of selection and (b) survey how transmissible tumours of dogs and Tasmanian devils provide naturally evolved tests of immune surveillance
Statistical modeling of ground motion relations for seismic hazard analysis
We introduce a new approach for ground motion relations (GMR) in the
probabilistic seismic hazard analysis (PSHA), being influenced by the extreme
value theory of mathematical statistics. Therein, we understand a GMR as a
random function. We derive mathematically the principle of area-equivalence;
wherein two alternative GMRs have an equivalent influence on the hazard if
these GMRs have equivalent area functions. This includes local biases. An
interpretation of the difference between these GMRs (an actual and a modeled
one) as a random component leads to a general overestimation of residual
variance and hazard. Beside this, we discuss important aspects of classical
approaches and discover discrepancies with the state of the art of stochastics
and statistics (model selection and significance, test of distribution
assumptions, extreme value statistics). We criticize especially the assumption
of logarithmic normally distributed residuals of maxima like the peak ground
acceleration (PGA). The natural distribution of its individual random component
(equivalent to exp(epsilon_0) of Joyner and Boore 1993) is the generalized
extreme value. We show by numerical researches that the actual distribution can
be hidden and a wrong distribution assumption can influence the PSHA negatively
as the negligence of area equivalence does. Finally, we suggest an estimation
concept for GMRs of PSHA with a regression-free variance estimation of the
individual random component. We demonstrate the advantages of event-specific
GMRs by analyzing data sets from the PEER strong motion database and estimate
event-specific GMRs. Therein, the majority of the best models base on an
anisotropic point source approach. The residual variance of logarithmized PGA
is significantly smaller than in previous models. We validate the estimations
for the event with the largest sample by empirical area functions. etc
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Measurements of the transverse-momentum-dependent cross sections of J /ψ production at mid-rapidity in proton+proton collisions at s =510 and 500 GeV with the STAR detector
We present measurements of the differential cross sections of inclusive J/ψ meson production as a function of transverse momentum (pTJ/ψ) using the μ+μ- and e+e- decay channels in proton+proton collisions at center-of-mass energies of 510 and 500 GeV, respectively, recorded by the STAR detector at the Relativistic Heavy Ion Collider. The measurement from the μ+μ- channel is for
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