Learning to love diligent trolls: Accounting for rater effects in the dialogue safety task

Chatbots have the risk of generating offensive utterances, which must be avoided. Post-deployment, one way for a chatbot to continuously improve is to source utterance/label pairs from feedback by live users. However, among users are trolls, who provide training examples with incorrect labels. To de-troll training data, previous work removed training examples that have high user-aggregated cross-validation (CV) error. However, CV is expensive; and in a coordinated attack, CV may be overwhelmed by trolls in number and in consistency among themselves. In the present work, I address both limitations by proposing a solution inspired by methodology in automated essay scoring (AES): have multiple users rate each utterance, then perform latent class analysis (LCA) to infer correct labels. As it does not require GPU computations, LCA is inexpensive. In experiments, I found that the AES-like solution can infer training labels with high accuracy when trolls are consistent, even when trolls are the majority.Comment: Accept-Findings at EMNLP 202

Identification of druggable small molecule antagonists of the Plasmodium falciparum hexose transporter PfHT and assessment of ligand access to the glucose permeation pathway via FLAG-mediated protein engineering

Although the Plasmodium falciparum hexose transporter PfHT has emerged as a promising target for anti-malarial therapy, previously identified small-molecule inhibitors have lacked promising drug-like structural features necessary for development as clinical therapeutics. Taking advantage of emerging insight into structure/function relationships in homologous facilitative hexose transporters and our novel high throughput screening platform, we investigated the ability of compounds satisfying Lipinksi rules for drug likeness to directly interact and inhibit PfHT. The Maybridge HitFinder chemical library was interrogated by searching for compounds that reduce intracellular glucose by >40% at 10 μM. Testing of initial hits via measurement of 2-deoxyglucose (2-DG) uptake in PfHT over-expressing cell lines identified 6 structurally unique glucose transport inhibitors. WU-1 (3-(2,6-dichlorophenyl)-5-methyl-N-[2-(4-methylbenzenesulfonyl)ethyl]-1,2-oxazole-4-carboxamide) blocked 2-DG uptake (IC50 = 5.8 ± 0.6 μM) with minimal effect on the human orthologue class I (GLUTs 1–4), class II (GLUT8) and class III (GLUT5) facilitative glucose transporters. WU-1 showed comparable potency in blocking 2-DG uptake in freed parasites and inhibiting parasite growth, with an IC50 of 6.1 ± 0.8 μM and EC50 of 5.5 ± 0.6 μM, respectively. WU-1 also directly competed for N-[2-[2-[2-[(N-biotinylcaproylamino)ethoxy)ethoxyl]-4-[2-(trifluoromethyl)-3H-diazirin-3-yl]benzoyl]-1,3-bis(mannopyranosyl-4-yloxy)-2-propylamine (ATB-BMPA) binding and inhibited the transport of D-glucose with an IC50 of 5.9 ± 0.8 μM in liposomes containing purified PfHT. Kinetic analysis revealed that WU-1 acts as a non-competitive inhibitor of zero-trans D-fructose uptake. Decreased potency for WU-1 and the known endofacial ligand cytochalasin B was observed when PfHT was engineered to contain an N-terminal FLAG tag. This modification resulted in a concomitant increase in affinity for 4,6-O-ethylidene-α-D-glucose, an exofacially directed transport antagonist, but did not alter the Km for 2-DG. Taken together, these data are consistent with a model in which WU-1 binds preferentially to the transporter in an inward open conformation and support the feasibility of developing potent and selective PfHT antagonists as a novel class of anti-malarial drugs.</div

A goodness-of-fit test for the bivariate necessary-but-not-sufficient relationship

In the social sciences, theory often casts bivariate relationships between constructs in terms of logical asymmetries. For example, in psychology, one theory is that intelligence is necessary but not sufficient for creativity. But as average-based linear models fail to accommodate nuances of logical asymmetries, a mismatch between theory and method is common in the literature. Recent methodological work proposed the Linear Ceiling and Floor Probability Region (LCFPR) model, which analyzes bivariate relationships in terms of necessity and sufficiency. However, an erroneous treatment of nested models and a lack of a formal goodness-of-fit test remain unaddressed in the LCFPR framework. In this thesis, I propose a goodness-of-fit test for LCFPR that addresses such shortcomings. A simulation study shows that, using a nonparametric quantile, the power and size of the test are largely acceptable. Analyses of real datasets demonstrate the proposed procedure. Conclusions and future directions are outlined in the final chapter

Talk recordings

Videos of presentations by Michael John Ilagan

Model-agnostic unsupervised detection of bots in a Likert-type questionnaire

To detect bots in online survey data, there is a wealth of literature on statistical detection using only responses to Likert-type items. There are two traditions in the literature. One tradition requires labeled data, forgoing strong model assumptions. The other tradition requires a measurement model, forgoing collection of labeled data. In the present article, we consider the problem where neither requirement is available, for an inventory that has the same number of Likert-type categories for all items. We propose a bot detection algorithm that is both model-agnostic and unsupervised. Our proposed algorithm involves a permutation test with leave-one-out calculations of outlier statistics. For each respondent, it outputs a p-value for the null hypothesis that the respondent is a bot. Such an algorithm offers nominal sensitivity calibration that is robust to the bot response distribution. In a simulation study, we found our proposed algorithm to improve upon naive alternatives in terms of 95% sensitivity calibration and, in many scenarios, in terms of classification accuracy

Feasibility of telerehabilitation in the community-oriented rehabilitation program of the College of Rehabilitation Sciences in Brgy. Kabulusan, Gen. Emilio Aguinaldo, Cavite

A descriptive quantitative and qualitative study was conducted in coordination with the residents and local government unit of Brgy. Kabulusan, members of the academe of DLSHSI College of Rehabilitation Sciences and IT experts in the Institute, and a private telecommunication company. Non-probability purposive sampling based on the inclusion and exclusion criteria was used in this study. Three (3) separate dates were scheduled to meet each of the three (3) groups of respondents to introduce the concept of telerehabilitation with the use of a brochure and a Powerpoint presentation. Self-administered survey questionnaires were then distributed after the orientation. The survey questionnaires were answered using a 5-point Likert scale and were analyzed statistically through frequency distribution, mean and percentage. The results of the feasibility study showed that a telerehabilitation infrastructure in Brgy. Kabulusan, Gen. Emilio Aguinaldo, Cavite is feasible to a great extent. Specifically, data showed that the project is feasible to a great extent as to technical and financial requirements and feasible to a great extent as to level of acceptance from the members of the community, the local government unit, members of the academe, IT experts, and the private sector. Qualitative data gathered from the study showed that implementing a telerehabilitation in Brgy. Kabulusan would improve the way of providing physical therapy services in a rural area. Consultation, assessment, intervention, and re-evaluation would be faster and easier through the use of videoconferencing, e-mail and mobile messaging for the clients, interns, barangay health workers, and local government unit. However, on the part of the physical therapist, they might come up with the wrong assessment through the use of such technology. In terms of the telerehabilitation infrastructure, the IT experts recommend the ideal requirements more than the minimum requirements. Moreover, the private company is willing and capable to finance the ideal requirements and that they could provide telerehabilitation software and faster internet connection. In conclusion, the results indicate that establishing a telerehabilitation infrastructure in a rural CoRP community like Brgy. Kabulusan, Gen. Emilio Aguinaldo, Cavite is feasible

H3B-8800, an orally available small-molecule splicing modulator, induces lethality in spliceosome-mutant cancers

Genomic analyses of cancer have identified recurrent point mutations in the RNA splicing factor-encoding genes SF3B1, U2AF1, and SRSF2 that confer an alteration of function(1-6). Cancer cells bearing these mutations are preferentially dependent on wild-type (WT) spliceosome function(7-11), but clinically relevant means to therapeutically target the spliceosome do not currently exist. Here we describe an orally available modulator of the SF3b complex, H3B-8800, which potently and preferentially kills spliceosome-mutant epithelial and hematologic tumor cells. These killing effects of H3B-8800 are due to its direct interaction with the SF3b complex, as evidenced by loss of H3B-8800 activity in drug-resistant cells bearing mutations in genes encoding SF3b components. Although H3B-8800 modulates WT and mutant spliceosome activity, the preferential killing of spliceosome-mutant cells is due to retention of short, GC-rich introns, which are enriched for genes encoding spliceosome components. These data demonstrate the therapeutic potential of splicing modulation in spliceosome-mutant cancers