455 research outputs found
Quantitative analysis of human kallikrein gene 14 expression in breast tumours indicates association with poor prognosis
KLK14 (formerly known as KLK-L6) is a recently identified member of the human kallikrein gene family. This family harbours several genes aberrantly expressed in various cancers as well as established (PSA/hK3, hK2) and potential (hK6, hK10) cancer markers. Similar to other kallikrein genes, KLK14 was found to be regulated by steroid hormones, particularly androgens and progestins, in breast and ovarian cancer cell lines. Preliminary studies indicated that KLK14 is differentially expressed in breast, ovarian, prostatic and testicular tumours. Given the above, we determined the prognostic significance of KLK14 expression in breast cancer. We studied KLK14 expression in 178 histologically confirmed epithelial breast carcinomas by quantitative reverse transcriptionâpolymerase chain reaction and correlated with clinicopathological variables (tumour stage, grade, histotype etc.) and with outcome (disease-free survival and overall survival), monitored over a median of 76 months. KLK14 mRNA levels ranged from 0 to 1219 arbitrary units in breast cancer tissues, with a meanÂąs.e. of 136Âą22. An optimal cutoff value of 40.5 arbitrary units was selected, to categorise tumours as KLK14-positive or negative. Higher concentrations of KLK14 mRNA were more frequently found in patients with advanced stage (III) disease (P=0.032). No statistically significant association was found between KLK14 and the other clinicopathological variables. KLK14 overexpression was found to be a significant predictor of decreased disease-free survival (hazard ratio of 2.31, P=0.001) and overall survival (hazard ratio of 2.21, P=0.005). Cox multivariate analysis indicated that KLK14 was an independent prognostic indicator of disease-free survival and overall survival. KLK14 also has independent prognostic value in subgroups of patients with a tumour size ⊽2âcm and positive nodal, oestrogen receptor and progestin receptor status. We conclude that KLK14 expression, as assessed by quantitative reverse transcriptionâpolymerase chain reaction, is an independent marker of unfavourable prognosis for breast cancer
Early-life adversity selectively impairs Îą2-GABAA receptor expression in the mouse nucleus accumbens and influences the behavioral effects of cocaine
Haplotypes of the Gabra2 gene encoding the Îą2-subunit of the GABAA receptor (GABAAR) are associated with drug abuse, suggesting that Îą2-GABAARs may play an important role in the circuitry underlying drug misuse. The genetic association of Gabra2 haplotypes with cocaine addiction appears to be evident primarily in individuals who had experienced childhood trauma. Given this association of childhood trauma, cocaine abuse and the Gabra2 haplotypes, we have explored in a mouse model of early life adversity (ELA) whether such events influence the behavioral effects of cocaine and if, as suggested by the human studies, Îą2-GABAARs in the nucleus accumbens (NAc) are involved in these perturbed behaviors. In adult mice prior ELA caused a selective decrease of accumbal Îą2-subunit mRNA, resulting in a selective decrease in the number and size of the Îą2-subunit (but not the Îą1-subunit) immunoreactive clusters in NAc core medium spiny neurons (MSNs). Functionally, in adult MSNs ELA decreased the amplitude and frequency of GABAAR-mediated miniature inhibitory postsynaptic currents (mIPSCs), a profile similar to that of Îą2 âknock-outâ (Îą2â/â) mice. Behaviourally, adult male ELA and Îą2â/â mice exhibited an enhanced locomotor response to acute cocaine and blunted sensitisation upon repeated cocaine administration, when compared to their appropriate controls. Collectively, these findings reveal a neurobiological mechanism which may relate to the clinical observation that early trauma increases the risk for substance abuse disorder (SAD) in individuals harbouring haplotypic variations in the Gabra2 gene
Entrepreneurial sons, patriarchy and the Colonels' experiment in Thessaly, rural Greece
Existing studies within the field of institutional entrepreneurship explore how entrepreneurs influence change in economic institutions. This paper turns the attention of scholarly inquiry on the antecedents of deinstitutionalization and more specifically, the influence of entrepreneurship in shaping social institutions such as patriarchy. The paper draws from the findings of ethnographic work in two Greek lowland village communities during the military Dictatorship (1967â1974). Paradoxically this era associated with the spread of mechanization, cheap credit, revaluation of labour and clear means-ends relations, signalled entrepreneurial sonsâ individuated dissent and activism who were now able to question the Patriarchâs authority, recognize opportunities and act as unintentional agents of deinstitutionalization. A âdifferentâ model of institutional change is presented here, where politics intersects with entrepreneurs, in changing social institutions. This model discusses the external drivers of institutional atrophy and how handling dissensus (and its varieties over historical time) is instrumental in enabling institutional entrepreneurship
Using role-play to improve studentsâ confidence and perceptions of communication in a simulated volcanic crisis
Traditional teaching of volcanic science typically emphasises scientific
principles and tends to omit the key roles, responsibilities, protocols, and
communication needs that accompany volcanic crises. This chapter
provides a foundation in instructional communication, education, and risk
and crisis communication research that identifies the need for authentic
challenges in higher education to challenge learners and provide
opportunities to practice crisis communication in real-time. We present
an authentic, immersive role-play called the Volcanic Hazards Simulation
that is an example of a teaching resource designed to match professional
competencies. The role-play engages students in volcanic crisis concepts
while simultaneously improving their confidence and perceptions of
communicating science. During the role-play, students assume authentic
roles and responsibilities of professionals and communicate through
interdisciplinary team discussions, media releases, and press conferences.
We characterised and measured the studentsâ confidence and perceptions
of volcanic crisis communication using a mixed methods research design
to determine if the role-play was effective at improving these qualities.
Results showed that there was a statistically significant improvement in
both communication confidence and perceptions of science communication.
The exercise was most effective in transforming low-confidence and
low-perception students, with some negative changes measured for our
higher-learners. Additionally, students reported a comprehensive and
diverse set of best practices but focussed primarily on the mechanics of
science communication delivery. This curriculum is a successful example
of how to improve studentsâ communication confidence and perceptions
MicroRNA-Restricted Transgene Expression in the Retina
Background: Gene transfer using adeno-associated viral (AAV) vectors has been successfully applied in the retina for the treatment of inherited retinal dystrophies. Recently, microRNAs have been exploited to fine-tune transgene expression improving therapeutic outcomes. Here we evaluated the ability of retinal-expressed microRNAs to restrict AAV-mediated transgene expression to specific retinal cell types that represent the main targets of common inherited blinding conditions. Methodology/Principal Findings: To this end, we generated AAV2/5 vectors expressing EGFP and containing four tandem copies of miR-124 or miR-204 complementary sequences in the 39UTR of the transgene expression cassette. These vectors were administered subretinally to adult C57BL/6 mice and Large White pigs. Our results demonstrate that miR-124 and miR-204 target sequences can efficiently restrict AAV2/5-mediated transgene expression to retinal pigment epithelium and photoreceptors, respectively, in mice and pigs. Interestingly, transgene restriction was observed at low vector doses relevant to therapy. Conclusions: We conclude that microRNA-mediated regulation of transgene expression can be applied in the retina to either restrict to a specific cell type the robust expression obtained using ubiquitous promoters or to provide an additiona
Learning from data to predict future symptoms of oncology patients
Effective symptom management is a critical component of cancer treatment. Computational tools that predict the course and severity of these symptoms have the potential to assist oncology clinicians to personalize the patientâs treatment regimen more efficiently and provide more aggressive and timely interventions. Three common and inter-related symptoms in cancer patients are depression, anxiety, and sleep disturbance. In this paper, we elaborate on the efficiency of Support Vector Regression (SVR) and Non-linear Canonical Correlation Analysis by Neural Networks (n-CCA) to predict the severity of the aforementioned symptoms between two different time points during a cycle of chemotherapy (CTX). Our results demonstrate that these two methods produced equivalent results for all three symptoms. These types of predictive models can be used to identify high risk patients, educate patients about their symptom experience, and improve the timing of pre-emptive and personalized symptom management interventions
Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV
The performance of muon reconstruction, identification, and triggering in CMS
has been studied using 40 inverse picobarns of data collected in pp collisions
at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection
criteria covering a wide range of physics analysis needs have been examined.
For all considered selections, the efficiency to reconstruct and identify a
muon with a transverse momentum pT larger than a few GeV is above 95% over the
whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4,
while the probability to misidentify a hadron as a muon is well below 1%. The
efficiency to trigger on single muons with pT above a few GeV is higher than
90% over the full eta range, and typically substantially better. The overall
momentum scale is measured to a precision of 0.2% with muons from Z decays. The
transverse momentum resolution varies from 1% to 6% depending on pseudorapidity
for muons with pT below 100 GeV and, using cosmic rays, it is shown to be
better than 10% in the central region up to pT = 1 TeV. Observed distributions
of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO
Training in crisis communication and volcanic eruption forecasting:Design and evaluation of an authentic role-play simulation
We present an interactive, immersive, authentic role-play simulation designed to teach tertiary geoscience students
in New Zealand to forecast and mitigate a volcanic crisis. Half of the participating group (i.e., the Geoscience Team)
focuses on interpreting real volcano monitoring data (e.g., seismographs, gas output etc.) while the other half of the
group (i.e., the Emergency Management Team) forecasts and manages likely impacts, and communicates emergency
response decisions and advice to local communities. These authentic learning experiences were aimed at enhancing
upper-year undergraduate studentsâ transferable and geologic reasoning skills. An important goal of the simulation was
specifically to improve studentsâ science communication through interdisciplinary team discussions, jointly prepared,
and delivered media releases, and real-time, high-pressure, press conferences.
By playing roles, students experienced the specific responsibilities of a professional within authentic organisational
structures. A qualitative, design-based educational research study was carried out to assess the overall student experience
and self-reported learning of skills. A pilot and four subsequent iterations were investigated.
Results from this study indicate that students found these role-plays to be a highly challenging and engaging learning
experience and reported improved skills. Data from classroom observations and interviews indicate that the students
valued the authenticity and challenging nature of the role-play although personal experiences and team dynamics
(within, and between the teams) varied depending on the studentsâ background, preparedness, and personality.
During early iterations, observation and interviews from students and instructors indicate that some of the goals of the
simulation were not fully achieved due to: A) lack of preparedness, B) insufficient time to respond appropriately, C)
appropriateness of roles and team structure, and D) poor communication skills. Small modifications to the design of
Iterations 3 and 4 showed an overall improvement in the studentsâ skills and goals being reached.
A communication skills instrument (SPCC) was used to measure self-reported pre- and post- communication competence
in the last two iterations. Results showed that this instrument recorded positive shifts in all categories of self-perceived
abilities, the largest shifts seen in students who participated in press conferences. Future research will be aimed
at adapting this curricula to new volcanic and earthquake scenarios
Atrial arrhythmogenicity in aged Scn5a+/âKPQ mice modeling long QT type 3 syndrome and its relationship to Na+ channel expression and cardiac conduction
Recent studies have reported that human mutations in Nav1.5 predispose to early age onset atrial arrhythmia. The present experiments accordingly assess atrial arrhythmogenicity in aging Scn5a+/âKPQ mice modeling long QT3 syndrome in relationship to cardiac Na+ channel, Nav1.5, expression. Atrial electrophysiological properties in isolated Langendorff-perfused hearts from 3- and 12-month-old wild type (WT), and Scn5a+/âKPQ mice were assessed using programmed electrical stimulation and their Nav1.5 expression assessed by Western blot. Cardiac conduction properties were assessed electrocardiographically in intact anesthetized animals. Monophasic action potential recordings demonstrated increased atrial arrhythmogenicity specifically in aged Scn5a+/ÎKPQ hearts. These showed greater action potential duration/refractory period ratios but lower atrial Nav1.5 expression levels than aged WT mice. Atrial Nav1.5 levels were higher in young Scn5a+/ÎKPQ than young WT. These levels increased with age in WT but not Scn5a+/ÎKPQ. Both young and aged Scn5a+/ÎKPQ mice showed lower heart rates and longer PR intervals than their WT counterparts. Young Scn5a+/ÎKPQ mice showed longer QT and QTc intervals than young WT. Aged Scn5a+/ÎKPQ showed longer QRS durations than aged WT. PR intervals were prolonged and QT intervals were shortened in young relative to aged WT. In contrast, ECG parameters were similar between young and aged Scn5a+/ÎKPQ. Aged murine Scn5a+/ÎKPQ hearts thus exhibit an increased atrial arrhythmogenicity. The differing Nav1.5 expression and electrocardiographic indicators of slowed cardiac conduction between Scn5a+/ÎKPQ and WT, which show further variations associated with aging, may contribute toward atrial arrhythmia in aged Scn5a+/ÎKPQ hearts
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