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Neoantigen burden and CD8 T cell infiltrate are associated with clinical outcome in pancreatic ductal adenocarcinoma (PDAC). A shortcoming of many genetic models of PDAC is the lack of neoantigen burden and limited T cell infiltrate. The goal of the present study was to develop clinically relevant models of PDAC by inducing cancer neoantigens in KP2, a cell line derived from the KPC model of PDAC. KP2 was treated with oxaliplatin and olaparib (OXPARPi), and a resistant cell line was subsequently cloned to generate multiple genetically distinct cell lines (KP2-OXPARPi clones). Clones A and E are sensitive to immune checkpoint inhibition (ICI), exhibit relatively high T cell infiltration, and have significant upregulation of genes involved in antigen presentation, T cell differentiation, and chemokine signaling pathways. Clone B is resistant to ICI and is similar to the parental KP2 cell line in terms of relatively low T cell infiltration and no upregulation of genes involved in the pathways noted above. Tumor/normal exome sequencing and in silico neoantigen prediction confirms successful generation of cancer neoantigens in the KP2-OXPARPi clones and the relative lack of cancer neoantigens in the parental KP2 cell line. Neoantigen vaccine experiments demonstrate that a subset of candidate neoantigens are immunogenic and neoantigen synthetic long peptide vaccines can restrain Clone E tumor growth. Compared to existing models, the KP2-OXPARPi clones better capture the diverse immunobiology of human PDAC and may serve as models for future investigations in cancer immunotherapies and strategies targeting cancer neoantigens in PDAC.

Prediction, a prospective cognitive process, is increasingly believed to be crucial for adult cognition and learning. Despite decades of targeted research on prediction in adults, methodological limitations still exist for investigating prediction in infancy. In this article, we argue that pupillometry, or the measurement of pupil size, is an effective method to examine predictive processing in infants and will expand on existing methods (namely looking time and anticipatory eye movements). In particular, we argue that there are three specific features of pupillometry that make it particularly useful for augmenting the investigation of prediction in infancy. First, pupillometry has excellent temporal resolution that will facilitate the differentiation of prediction subcomponents. Second, pupillometry is highly continuous across the life span, allowing researchers to directly compare responses between infants and adults using an identical paradigm. Third, pupillometry can be used in conjunction with other behavioral measures, allowing for different yet complementary results. In addition, we review relevant adult and infant pupillometry studies that will facilitate infancy researchers to adopt this technique. Overall, pupillometry is particularly useful in investigating prediction in infancy and opens up several avenues for developmental research.

Certain transformations must occur within the brain to allow rapid processing of familiar experiences. Complex objects are thought to become unitized, whereby multifeature conjunctions are retrieved as rapidly as a single feature. Behavioral studies strongly support unitization theory, but a compelling neural mechanism is lacking. Here, we examined how unitization transforms conjunctive representations to become more “feature-like” by recruiting posterior regions of the ventral visual stream (VVS) whose architecture is specialized for processing single features. We used functional magnetic resonance imaging to scan humans before and after visual training with novel objects. We implemented a novel multivoxel pattern analysis to measure a conjunctive code, which represented a conjunction of object features above and beyond the sum of the parts. Importantly, a multivoxel searchlight showed that the strength of conjunctive coding in posterior VVS increased posttraining. Furthermore, multidimensional scaling revealed representational separation at the level of individual features in parallel to the changes at the level of feature conjunctions. Finally, functional connectivity between anterior and posterior VVS was higher for novel objects than for trained objects, consistent with early involvement of anterior VVS in unitizing feature conjunctions in response to novelty. These data demonstrate that the brain implements unitization as a mechanism to refine complex object representations over the course of multiple learning experiences.

Majority of visual statistical learning (VSL) research uses only offline measures, collected after the familiarization phase (i.e., learning) has occurred. Offline measures have revealed a lot about the extent of statistical learning (SL) but less is known about the learning mechanisms that support VSL. Studies have shown that prediction can be a potential learning mechanism for VSL, but it is difficult to examine the role of prediction in VSL using offline measures alone. Pupil diameter is a promising online measure to index prediction in VSL because it can be collected during learning, requires no overt action or task and can be used in a wide-range of populations (e.g., infants and adults). Furthermore, pupil diameter has already been used to investigate processes that are part of prediction such as prediction error and updating. While the properties of pupil diameter have the potentially to powerfully expand studies in VSL, through a series of three experiments, we find that the two are not compatible with each other. Our results revealed that pupil diameter, used to index prediction, is not related to offline measures of learning. We also found that pupil differences that appear to be a result of prediction, are actually a result of where we chose to baseline instead. Ultimately, we conclude that the fast-paced nature of VSL paradigms make it incompatible with the slow nature of pupil change. Therefore, our findings suggest pupillometry should not be used to investigate learning mechanisms in fast-paced VSL tasks.

Binding relations among items in the transverse patterning (TP) task is dependent on the integrity of the hippocampus and its extended network. Older adults have impaired TP learning, corresponding to age-related reductions in hippocampal volumes. Unitization is a training strategy that can mitigate TP impairments in amnesia by reducing reliance on hippocampal-dependent relational binding and increasing reliance on fused representations. Here we examined whether healthy older adults and those showing early signs of cognitive decline would also benefit from unitization. Although both groups of older adults had neuropsychological performance within the healthy range, their TP learning differed both under standard and unitized training conditions. Healthy older adults with impaired TP learning under standard training benefited from unitized training. Older adults who failed the Montreal Cognitive Assessment (MoCA) showed greater impairments under standard conditions, and showed no evidence of improvement with unitization. These individuals’ failures to benefit from unitization may be a consequence of early deficits not seen in older adults who pass the MoCA.

Adults use both bottom-up sensory inputs and top-down signals to generate predictions about future sensory inputs. Infants have also been shown to make predictions with simple stimuli and recent work has suggested top-down processing is available early in infancy. However, it is unknown whether this indicates that top-down prediction is an ability that is continuous across the lifespan or whether an infant's ability to predict is different from an adult's, qualitatively or quantitatively. We employed pupillometry to provide a direct comparison of prediction abilities across these disparate age groups. Pupil dilation response (PDR) was measured in 6-month olds and adults as they completed an identical implicit learning task designed to help learn associations between sounds and pictures. We found significantly larger PDR for visual omission trials (i.e. trials that violated participants' predictions without the presentation of new stimuli to control for bottom-up signals) compared to visual present trials (i.e. trials that confirmed participants' predictions) in both age groups. Furthermore, a computational learning model that is closely linked to prediction error (Rescorla-Wagner model) demonstrated similar learning trajectories suggesting a continuity of predictive capacity and learning across the two age groups.

Recently, strategies beyond pharmacological and psychological treatments have been developed for the management of obsessive-compulsive disorder (OCD). Specifically, repetitive transcranial magnetic stimulation (rTMS) has been employed as an adjunctive treatment in cases of treatment-refractory OCD. Here, we investigate six weeks of low frequency rTMS, applied bilaterally and simultaneously over the sensory motor area, in OCD patients in a randomized, double-blind placebo-controlled clinical trial. Twenty-two participants were randomly enrolled into the treatment (ACTIVE = 10) or placebo (SHAM = 12) groups. At each of seven visits (baseline; day 1 and weeks 2, 4, and 6 of treatment; and two and six weeks after treatment) the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) was administered. At the end of the six weeks of rTMS, patients in the ACTIVE group showed a clinically significant decrease in Y-BOCS scores compared to both the baseline and the SHAM group. This effect was maintained six weeks following the end of rTMS treatment. Therefore, in this sample, rTMS appeared to significantly improve the OCD symptoms of the treated patients beyond the treatment window. More studies need to be conducted to determine the generalizability of these findings and to define the duration of rTMS’ clinical effect on the Y-BOCS. Clinical Trial Registration Number (NCT) at www.clinicaltrials.gov: NCT00616486.

In Australia, postgraduate international student enrolments have risen 81 per cent since 2002. In 2008, 74 per cent of international enrolments were in Business/Management, Computer Science and Engineering-related courses (Davies, 2010). Most international students are from Asia, and the vast majority of those from mainland China. A survey of employers in 2006 found that employers rated interpersonal and communications skills (written, oral, listening) far above “qualifications” and “previous employment” as the most important selection criteria when hiring graduates (Davies, 2010). In fact, research on the IELTS levels of exiting Master’s degree students suggests that international students at Australian universities tended to graduate with worse spoken English skills than when they first entered.The above research has identified a deficiency in the communication skills of international students, crucial in seeking employment. This chapter proposes various ways of helping committed international students on campus to improve their spoken English language by combining the use of the students’ bodies with mobile technology.

This chapter examines the reliability and validity of a subset of the Genetics concept inventory (S. Elrod) to discriminate good students from poor performing students in the undergraduate units Genetics and Molecular Biology taught at the University of Canberra, Australia. These two units went through a series of reforms since 2005. These reforms included the implementation of a number of online and tutorial language exercises and strategies designed to promote scientific language competence and subsequent genetics learning. The effect of these interventions was analyzed through grade and assessment performance comparisons with earlier traditionally taught Genetics cohorts as well using the genetic concept inventory. The genetic concept inventory questions used at the University of Canberra have been found to be reliable and valid according to a number of statistical tests.

This chapter contains findings from the preceding chapters in r the project addressing language difficulties in science education in large classes.

This chapter aims to explore the effect of providing multiple sources of feedback through a language teaching approach called the Somatically-enhanced Approach (SEA) (Zhang, 2006) in the teaching of Thai language to foreigners. Teaching innovations include: the use of relaxation techniques to relax students; the use of humming, clapping, mouthing, and physical gestures to emphasize the rhythm of the Thai language; the use of a Speech comparison tool (Sptool) for providing biofeedback; and the provision of all learning materials on CDs. Two groups of students were involved in the study. An experimental group (EG) consisted of 24 international students who enrolled in the Thai Language for Foreigners course at Khon Kaen University, Thailand. These students came from People’s Republic of China, Vietnam, and Laos. They were taught using SEA. The control group (CG) consisted of 22 Chinese students who studied Thai language at Guangxi University for Nationalities, China, taught with the traditional method. The results of this study revealed that after 24 face-to-face contact hours over 8 weeks, international students who undertook a course in SEA spoke more fluently than the control group who studied Thai for 44 hours over 11 weeks. The differences in the quality and quantity of speech were statistically significant. The results of the study, both quantitative and qualitative, will be reported. The improved gains in students’ performance in EG can be attributed to the multiple sources of feedback afforded by SEA.

As English has been increasingly recognized as one of the influential factors for China in taking parts in global community, students and Chinese professionals need to participate in international seminars and conferences, and internationally collaborate with academics through the lingua franca, English. Hence, being able to speak intelligible English has unavoidably become a necessity, especially for Chinese university students. The purpose of this chapter focuses on the implementation of constructive role plays (CRP) via the NHCE e-learning in learning English as a foreign language classes. This chapter exploits quantitative and qualitative methods such as pretest, post-test, student questionnaires and student role play recording analysis to collect data to demonstrate the effectiveness of CRP on Chinese university students’ spoken English development. Results showed that there was a significant increase in the students’ speaking proficiency for the experimental group as compared to the control group. The results also indicated that CRP has been highly successful as an effective aid in improving EFL students’ speaking. The NHCE e-learning platform can provide a motivating environment for L2 students to practice spoken English. However, the empirical results showed that the use of online audio chat facility to perform the CRP may make some students feel anxious, due to its synchronized nature. This suggests that its use should be carefully considered in relation to divergent groups of learners.

The chapter discusses the background of a project which aimed at addressing the language needs of a diverse student body (both domestic and international student body) by embedding strategic approaches to learning and teaching in first year sciences in tertiary education. These strategies consisted of active learning skills which are widely used in language learning. The disciplines covered by the project were Biology, Chemistry and Physics and involved the University of Canberra, University of Sydney, University of Tasmania, University of Technology, Sydney, and University of Newcastle in Australia. This project was funded by the Australian Learning and Teaching Council (ALTC).

This chapter focuses on the effect of a learning environment in which biological, physical and technological ways of perceiving Mandarin Chinese sounds have been used. One of the most important tools of this environment is the use of a speech analysis tool for audio and visual feedback. This is done by way of incorporating a visual representation of student’s production that can be easily compared to the speech of a native speaker. It is the contention of this chapter that such an interactive feedback tool in conjunction with other feedback mechanisms can provide opportunities for increasing the effectiveness of feedback in language learning.

This chapter reports on a study which evaluates the effect of a language teaching approach called the Somatically-Enhanced Approach (Zhang, 2006)in the teaching of Thai to Vietnamese learners in Vietnam. The teaching methodology deals with training students’ pronunciation in Thai from the beginning. Innovations include: the using relaxation techniques to relax students; the use of humming, clapping and physical gestures to emphasize the rhythm of Thai; the use of a Speech comparison tool (Sptool) (Zhang & Newman, 2003) and the provision of all learning materials on CD-ROMs. Results show that after 12 face-to-face hours, Vietnamese students who undertook an intensive course in SEA achieved the same level of fluency in spoken Thai, in limited contexts, as their fellow students who studied Thai for 1 year using the traditional approach. Both quantitative and qualitative results of the study will be briefly reported including an evaluation of the Speech comparison tool.

Language learning is one of the most rapidly changing disciplines. Along with changing perspectives in learning in the field of Second Language Acquisition, information communication technology (ICT) has also created many learning paths to assist the process of learning a second language (L2). In such an ever-evolving environment, teachers, researchers, and professionals in a diverse number of disciplines need access to the most current information about research on the field of computer-enhanced language acquisition and learning. The Handbook of Research on Computer-Enhanced Language Acquisition and Learning provides comprehensive coverage of successful translation of language learning designs utilizing ICT in practical learning contexts. This authoritative reference source offers researchers, scholars, students, and professionals worldwide, access to the latest knowledge related to research on computer-enhanced language acquisition and learning.

To address the global problems of learning, we must make our development strategies ready to support the many different languages and cultures in the world. This chapter discusses how the Irvine-Geneva development strategy supports, and can be made to support further, development of global materials. We will first discuss essential characteristics of the kind of learning software that will successfully address global education. We will then discuss our design and translation strategies for current software with those characteristics, the tools we have developed for facilitating them, and our implementation strategies. We will end our discussion with linguistics issues related to globalization in general.

The purpose of this article is to describe a language-learning environment for beginning Chinese learners in Australia in which technology plays a crucial role in the overall planning of the curriculum. In this curriculum priority had been given to listening and speaking skills rather than helping learners to learn through reading romanization of the Chinese language. The integration of computer enhanced learning materials in the curriculum not only provided easy access to the pronunciation.

One of the emerging issues is the changing nature and diversity of students in science. The project, ‘A cross-­disciplinary approach to language support for first year students in the physical sciences’, commenced in October, 2007 and was funded by the Australian Learning and Teaching Council (ALTC), to address the language needs of a diverse student body by investigating and testing strategic approaches to learning and teaching in First Year sciences. This project was concerned with the acquisition of language specific to science (rather than for science students to write grammatically correct sentences or improve language use for ESL students) and the implicit teaching of meta-­cognitive skills required in doing science. Eight strategies were employed in five universities and a number of positive outcomes have been obtained. Most noticeably, the demonstrable gains achieved by students at every university and in every discipline. Students’ perception of lecturers’ ability to teach has dra-­ matically improved. The project is sustainable on student learning through affecting lecturer expertise in using these language strategies. It provides a successful and achievable model for sustainable professional development of academic staff.