Utilizing Muscovite to Create High Mobility Molybdenum Disulfide Transistors

Molybdenum disulfide transistor devices were fabricated utilizing muscovite mica as dielectrics in order to test the hydrophilic behavior of mica. This was done by probing the device for its transconductance plot to show hysteretic patterns. Devices were fabricated using a clean van der Waals technique to stack two-dimensional materials into heterostructures. The devices showed a hysteretic trend in the transconductance curve. We compared the hysteretic behavior from mica with that of another well-known dielectric, silicon dioxide. The devices with mica dielectrics showed larger hysteresis in the gate sweeps than silicon dioxide. Devices utilizing mica as dielectrics are expected to have hysteretic behaviors due to the interfacial water on the mica surface. It is also speculated that water accumulation will continue to grow on the surface as long as the device is in ambient conditions, so the hysteresis may worsen over time. We aim to mitigate water absorption at the surface of mica and suggest future work to accomplish this goal.https://digitalscholarship.unlv.edu/durep_podium/1020/thumbnail.jp

Phosphatidylinositol 3-Kinase Couples Localised Calcium Influx to Activation of Akt in Central Nerve Terminals

The efficient retrieval of synaptic vesicle membrane and cargo in central nerve terminals is dependent on the efficient recruitment of a series of endocytosis modes by different patterns of neuronal activity. During intense neuronal activity the dominant endocytosis mode is activity-dependent endocytosis (ADBE). Triggering of ADBE is linked to calcineurin-mediated dynamin I dephosphorylation since the same stimulation intensities trigger both. Dynamin I dephosphorylation is maximised by a simultaneous inhibition of its kinase glycogen synthase kinase 3 (GSK3) by the protein kinase Akt, however it is unknown how increased neuronal activity is transduced into Akt activation. To address this question we determined how the activity-dependent increases in intracellular free calcium ([Ca(2+)](i)) control activation of Akt. This was achieved using either trains of high frequency action potentials to evoke localised [Ca(2+)](i) increases at active zones, or a calcium ionophore to raise [Ca(2+)](i) uniformly across the nerve terminal. Through the use of either non-specific calcium channel antagonists or intracellular calcium chelators we found that Akt phosphorylation (and subsequent GSK3 phosphorylation) was dependent on localised [Ca(2+)](i) increases at the active zone. In an attempt to determine mechanism, we antagonised either phosphatidylinositol 3-kinase (PI3K) or calmodulin. Activity-dependent phosphorylation of both Akt and GSK3 was arrested on inhibition of PI3K, but not calmodulin. Thus localised calcium influx in central nerve terminals activates PI3K via an unknown calcium sensor to trigger the activity-dependent phosphorylation of Akt and GSK3

Cervical screening with primary HPV testing or cytology in a population of women in which those aged 33 years or younger had previously been offered HPV vaccination: Results of the Compass pilot randomised trial

<div><p>Background</p><p>Using primary human papillomavirus (HPV) testing for cervical screening increases detection of high-grade cervical intraepithelial neoplastic lesions and invasive cancer (cervical intraepithelial neoplasia grade 2+ [CIN2+]) compared to cytology, but no evaluation has been conducted in a population previously offered HPV vaccination. We aimed to assess colposcopy referral and CIN2+ detection rates for HPV-screened versus cytology-screened women in Australia’s HPV-vaccinated population (by 2014, resident women ≤33 years had been age-eligible for HPV vaccination, with 3-dose uptake across age cohorts being about 50%–77%).</p><p>Methods and findings</p><p>Compass is an open-label randomised trial of 5-yearly HPV screening versus 2.5-yearly liquid-based cytology (LBC) screening. In the first phase, consenting women aged 25–64 years presenting for routine screening at 47 primary practices in Victoria, Australia, provided a cervical sample and were randomised at a central laboratory at a 1:2:2 allocation to (i) image-read LBC screening with HPV triage of low-grade cytology (‘LBC screening’), (ii) HPV screening with those HPV16/18 positive referred to colposcopy and with LBC triage for other oncogenic (OHR) types (‘HPV+LBC triage’), or (iii) HPV screening with those HPV16/18 positive referred to colposcopy and with dual-stained cytology triage for OHR types (‘HPV+DS triage’). A total of 5,006 eligible women were recruited from 29 October 2013 to 7 November 2014 (recruitment rate 58%); of these, 22% were in the group age-eligible for vaccination. Data on 4,995 participants were analysed after 11 withdrawals; 998 were assigned to, and 995 analysed (99.7%) in, the LBC-screened group; 1,996 assigned to and 1,992 analysed (99.8%) in the HPV+LBC triage group; and 2,012 assigned to and 2,008 analysed (99.8%) in the HPV+DS triage group. No serious trial-related adverse events were reported. The main outcomes were colposcopy referral and detected CIN2+ rates at baseline screening, assessed on an intention-to-treat basis after follow-up of the subgroup of triage-negative women in each arm referred to 12 months of surveillance, and after a further 6 months of follow-up for histological outcomes (dataset closed 31 August 2016). Analysis was adjusted for whether women had been age-eligible for HPV vaccination or not. For the LBC-screened group, the overall referral and detected CIN2+ rates were 27/995 (2.7% [95% CI 1.8%–3.9%]) and 1/995 (0.1% [95% CI 0.0%–0.6%]), respectively; for HPV+LBC triage, these were 75/1,992 (3.8% [95% CI 3.0%–4.7%]) and 20/1,992 (1.0% [95% CI 0.6%–1.5%]) and 20/1,992 (1.0% [95% CI 0.6%–1.5%); and for HPV+DS triage, these were 79/2,008 (3.9% [95% CI 3.1%–4.9%]) and 24/2,008 (1.2% [95% CI 0.8%–1.6%]) (<i>p =</i> 0.09 for difference in referral rate in LBC versus all HPV-screened women; <i>p =</i> 0.003 for difference in CIN2+ detection rate in LBC versus all HPV-screened women, with <i>p =</i> 0.62 between HPV screening groups). Limitations include that the study population involved a relatively low risk group in a previously well-screened and treated population, that individual women’s vaccination status was unknown, and that long-term follow-up data on disease detection in screen-negative women are not yet available.</p><p>Conclusions</p><p>In this study, primary HPV screening was associated with significantly increased detection of high-grade precancerous cervical lesions compared to cytology, in a population where high vaccine uptake was reported in women aged 33 years or younger who were offered vaccination. It had been predicted that increased disease detection might be associated with a transient increase in colposcopy referral rates in the first round of HPV screening, possibly dampened by HPV vaccine effect; in this study, although the point estimates for referral rates in women in each HPV-screened group were 41%–44% higher than in cytology-screened women, the difference in referral rate between cytology- and HPV-screened women was not significant. These findings provide initial support for the implementation of primary HPV screening in vaccinated populations.</p><p>Trial registration</p><p>Australian New Zealand Clinical Trials Registry <a href="https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=364244" target="_blank">ACTRN12613001207707</a></p></div

Trial profile: CONSORT 2010 flow diagram.

<p>*The number of eligible women was estimated using the total number of samples sent to the Victorian Cytology Service for cervical screening from the participating clinics. Two recruiting clinics were excluded from this estimate as their non-Compass cervical cytology samples were processed through a different laboratory and thus their precise recruitment rate cannot be obtained. **A total of 5,303 women were initially recruited. ***A total of 297 women were subsequently found to be ineligible because of their age, or because they were currently in follow-up for a previously diagnosed low-grade or high-grade abnormality, or the consent form was not received at the laboratory. ****A further 11 women subsequently withdrew from the trial; these were excluded (1 expressed concerns about the longer interval for screening, 1 did not wish to participate in verification colposcopy, 1 was anxious, 1 moved overseas and requested to be withdrawn, and 7 did not provide specific reasons). This left a total of 4,995 eligible participants for the primary outcome analysis. HPV, human papillomavirus; LBC, liquid-based cytology.</p

Estimated colposcopy referral rates by study group.

<p>(i) Women age-eligible for vaccination (≤33 years in 2014) (N = 1,078). (ii) Women not age-eligible for vaccination (34+ years in 2014) (N = 3,917). (iii) All study participants (N = 4,995). Bars represent 95% confidence intervals. Arm 1: LBC screening; arm 2: HPV+LBC triage screening; arm 3: HPV+DS triage screening. DS, dual-stained; HPV, human papillomavirus; LBC, liquid-based cytology.</p

Case numbers and rates for detected CIN2+ and CIN3+, by age eligibility for vaccination.

<p>Case numbers and rates for detected CIN2+ and CIN3+, by age eligibility for vaccination.</p

PPVs for CIN2+ and CIN3+, by allocation group and referral pathway.

<p>PPVs for CIN2+ and CIN3+, by allocation group and referral pathway.</p