Neural response development during distributional learning.

We investigated online electrophysiological components of distributional learning, specifically of tones by listeners of a non-tonal language. German listeners were presented with a bimodal distribution of syllables with lexical tones from a synthesized continuum based on Cantonese level tones. Tones were presented in sets of four standards (within-category tokens) followed by a deviant (across-category token). Mismatch negativity (MMN) was measured. Earlier behavioral data showed that exposure to this bimodal distribution improved both categorical perception and perceptual acuity for level tones [1]. In the present study we present analyses of the electrophysiological response recorded during this exposure, i.e., the development of the MMN response during distributional learning. This development over time is analyzed using Generalized Additive Mixed Models and results showed that the MMN amplitude increased for both within- and across-category tokens, reflecting higher perceptual acuity accompanying category formation. This is evidence that learners zooming in on phonological categories undergo neural changes associated with more accurate phonetic perception.This research was also supported by a Research Networking grant (ESF) NetwordS No. 6609 to NB and a Leiden University AMT Individual Researcher Grant to JSN

Short-term exposure enhances perception of both between- and within-category acoustic information.

A critical question in speech research is how listeners use non-discrete acoustic cues for discrimination between discrete alternative messages (e.g. words). Previous studies have shown that distributional learning can improve listeners’ discrimination of non-native speech sounds. Less is known about effects of training on perception of within-category acoustic detail. The present research investigates adult listeners’ perception of and discrimination between lexical tones without training or after a brief training exposure. Native speakers of German (a language without lexical tone) heard a 13-step pitch continuum of the syllable /li:/. Two different tasks were used to assess sensitivity to acoustic differences on this continuum: a) pitch height estimation and b) AX discrimination. Participants performed these tasks either without exposure or after exposure to a bimodal distribution of the pitch continuum. The AX discrimination results show that exposure to a bimodal distribution enhanced discrimination at the category boundary (i.e. categorical perception) of high vs. low tones. Interestingly, the pitch estimation task results followed a categorisation (sigmoid) function without exposure, but a linear function after exposure, suggesting estimates became less categorical in this task. The results suggest that training exposure may enhance not only discrimination between contrastive speech sounds (consistent with previous studies), but also perception of withincategory acoustic differences. Different tasks may reveal different skills

FROM MOUSTACHES TO MY SPACES

Radical removal of malignant lesions may be improved using tumor-targeted dual-modality probes that contain both a radiotracer and a fluorescent label to allow for enhanced intraoperative delineation of tumor resection margins. Because pretargeting strategies yield high signal-to-background ratios, we evaluated the feasibility of a pretargeting strategy for intraoperative imaging in prostate cancer using an anti-TROP-2 x anti-HSG bispecific antibody (TF12) in conjunction with the dual-labeled diHSG peptide (RDC018) equipped with both a DOTA chelate for radiolabeling purposes and a fluorophore (IRdye800CW) to allow near-infrared optical imaging. Nude mice implanted s.c. with TROP-2-expressing PC3 human prostate tumor cells or with PC3 metastases in the scapular and suprarenal region were injected i.v. with 1 mg of TF12 and, after 16 hours of tumor accumulation and blood clearance, were subsequently injected with 10 MBq, 0.2 nmol/mouse of either (111)In-RDC018 or (111)In-IMP288 as a control. Two hours after injection, both microSPECT/CT and fluorescence images were acquired, both before and after resection of the tumor nodules. After image acquisition, the biodistribution of (111)In-RDC018 and (111)In-IMP288 was determined and tumors were analyzed immunohistochemically. The biodistribution of the dual-label RDC018 showed specific accumulation in the TROP-2-expressing PC3 tumors (12.4 +/- 3.7% ID/g at 2 hours postinjection), comparable with (111)In-IMP288 (9.1 +/- 2.8% ID/g at 2 hours postinjection). MicroSPECT/CT and near-infrared fluorescence (NIRF) imaging confirmed this TROP-2-specific uptake of the dual-label (111)In-RDC018 in both the s.c. and metastatic growing tumor model. In addition, PC3 metastases could be visualized preoperatively with SPECT/CT and could subsequently be resected by image-guided surgery using intraoperative NIRF imaging, showing the preclinical feasibility of pretargeted dual-modality imaging approach in prostate cancer

Mosquito and Drosophila entomobirnaviruses suppress dsRNA- and siRNA-induced RNAi

RNA interference (RNAi) is a crucial antiviral defense mechanism in insects, including the major mosquito species that transmit important human viruses. To counteract the potent antiviral RNAi pathway, insect viruses encode RNAi suppressors. However, whether mosquito-specific viruses suppress RNAi remains unclear. We therefore set out to study RNAi suppression by Culex Y virus (CYV), a mosquito-specific virus of the Birnaviridae family that was recently isolated from Culex pipiens mosquitoes. We found that the Culex RNAi machinery processes CYV double-stranded RNA (dsRNA) into viral small interfering RNAs (vsiRNAs). Furthermore, we show that RNAi is suppressed in CYV-infected cells and that the viral VP3 protein is responsible for RNAi antagonism. We demonstrate that VP3 can functionally replace B2, the well-characterized RNAi suppressor of Flock House virus. VP3 was found to bind long dsRNA as well as siRNAs and interfered with Dicer-2-mediated cleavage of long dsRNA into siRNAs. Slicing of target RNAs by pre-assembled RNA-induced silencing complexes was not affected by VP3. Finally, we show that the RNAi-suppressive activity of VP3 is conserved in Drosophila X virus, a birnavirus that persistently infects Drosophila cell cultures. Together, our data indicate that mosquito-specific viruses may encode RNAi antagonists to suppress antiviral RNAi

Arbovirus-Derived piRNAs Exhibit a Ping-Pong Signature in Mosquito Cells

The siRNA pathway is an essential antiviral mechanism in insects. Whether other RNA interference pathways are involved in antiviral defense remains unclear. Here, we report in cells derived from the two main vectors for arboviruses, Aedes albopictus and Aedes aegypti, the production of viral small RNAs that exhibit the hallmarks of ping-pong derived piwi-associated RNAs (piRNAs) after infection with positive or negative sense RNA viruses. Furthermore, these cells produce endogenous piRNAs that mapped to transposable elements. Our results show that these mosquito cells can initiate de novo piRNA production and recapitulate the ping-pong dependent piRNA pathway upon viral infection. The mechanism of viral-piRNA production is discussed

Using Policy Labs as a process to bring evidence closer to public policymaking: a guide to one approach

While robust evidence is one ingredient in the policymaking process, it is by no means the only one. Engaging with policymakers and the policymaking process requires collaborative working models, navigating through the experiences, values and perspectives of policymakers and other stakeholders, as well as communicating evidence in an accessible manner. As a response to these requirements, over recent years there has been proliferation of activities that engage producers of evidence (specifically, academics), policymakers, practitioners, and the public in policy formulation, implementation and evaluation. In this article, we describe one engagement approach for facilitating research evidence uptake into policy and practice—an activity called a ‘Policy Lab’—as conducted by the team at The Policy Institute at King’s College London on numerous policy challenges over the past four years. Drawing on our experience in running 15 Policy Labs between January 2015 and September 2019, we (a) provide a guide to how we have run Policy Labs, while sharing our learning on what has worked best in conducting them and (b) demonstrate how these labs can contribute to bringing evidence closer to policymaking, by comparing their characteristics to enablers for doing so identified in the literature. While this approach to Policy Labs is not the only one of its kind, we suggest that these types of Labs manifest characteristics identified in previous studies for influencing the policymaking process; namely: providing a forum for open, honest conversations around a policy topic; creating new networks, collaborations and partnerships between academics and policymakers; synthesising available evidence on a policy topic in a robust and accessible format; and providing timely access to evidence relevant to a policy issue. We recognise the limitations of measuring and evaluating how these Labs change policy in the long-term and recommend viewing the Policy Lab as part of a process for engaging evidence and policymaking and not an isolated activity. This process serves to build a coalition through participation of diverse communities (thereby establishing ‘trust’), work on the language and presentation of evidence (thereby enabling effective ‘translation’ of evidence) and engage policymakers early to respond when policy windows emerge (thereby taking into account ‘timing’ for creating policy action)