Do-Operation Guided Causal Representation Learning with Reduced Supervision Strength

Causal representation learning has been proposed to encode relationships between factors presented in the high dimensional data. However, existing methods suffer from merely using a large amount of labeled data and ignore the fact that samples generated by the same causal mechanism follow the same causal relationships. In this paper, we seek to explore such information by leveraging do-operation to reduce supervision strength. We propose a framework that implements do-operation by swapping latent cause and effect factors encoded from a pair of inputs. Moreover, we also identify the inadequacy of existing causal representation metrics empirically and theoretically and introduce new metrics for better evaluation. Experiments conducted on both synthetic and real datasets demonstrate the superiorities of our method compared with state-of-the-art methods.Comment: NeurIPS 2022 Workshop CML4Impact Workshop Camera Read

SW-VAE: Weakly Supervised Learn Disentangled Representation Via Latent Factor Swapping

Representation disentanglement is an important goal of representation learning that benefits various downstream tasks. To achieve this goal, many unsupervised learning representation disentanglement approaches have been developed. However, the training process without utilizing any supervision signal have been proved to be inadequate for disentanglement representation learning. Therefore, we propose a novel weakly-supervised training approach, named as SW-VAE, which incorporates pairs of input observations as supervision signals by using the generative factors of datasets. Furthermore, we introduce strategies to gradually increase the learning difficulty during training to smooth the training process. As shown on several datasets, our model shows significant improvement over state-of-the-art (SOTA) methods on representation disentanglement tasks

Shadow Datasets, New challenging datasets for Causal Representation Learning

Discovering causal relations among semantic factors is an emergent topic in representation learning. Most causal representation learning (CRL) methods are fully supervised, which is impractical due to costly labeling. To resolve this restriction, weakly supervised CRL methods were introduced. To evaluate CRL performance, four existing datasets, Pendulum, Flow, CelebA(BEARD) and CelebA(SMILE), are utilized. However, existing CRL datasets are limited to simple graphs with few generative factors. Thus we propose two new datasets with a larger number of diverse generative factors and more sophisticated causal graphs. In addition, current real datasets, CelebA(BEARD) and CelebA(SMILE), the originally proposed causal graphs are not aligned with the dataset distributions. Thus, we propose modifications to them

An Inactivated Bacterium (Paraprobiotic) Expressing \u3ci\u3eBacillus thuringiensis\u3c/i\u3e Cry5B as a Therapeutic for \u3ci\u3eAscaris\u3c/i\u3e and \u3ci\u3eParascaris\u3c/i\u3e spp. Infections in Large Animals

Ascaris and Parascaris are important parasites in the family Ascarididae, large, ubiquitous intestinal-dwelling nematodes infecting all classes of vertebrates. Parasitic nematode drug resistance in veterinary medicine and drug recalcitrance in human medicine are increasing worldwide, with few if any new therapeutic classes on the horizon. Some of these parasites are zoonotic, e.g., Ascaris is passed from humans to pigs and vice versa. The development of new therapies against this family of parasites would have major implications for both human and livestock health. Here we tested the therapeutic ability of a paraprobiotic or dead probiotic that expresses the Bacillus thuringiensis Cry5B protein with known anthelmintic properties, against zoonotic Ascaris suum and Parascaris spp. This paraprobiotic, known as IBaCC, intoxicated A. suum larvae in vitro and was highly effective in vivo against intestinal A. suum infections in a new mouse model for this parasite. Fermentation was scaled up to 350 l to treat pigs and horses. Single dose Cry5B IBaCC nearly completely cleared A. suum infections in pigs. Furthermore, single dose Cry5B IBaCC drove fecal egg counts in Parascaris-infected foals to zero, showing at least parity with, and potential superiority to, current efficacy of anthelmintics used against this parasite. Cry5B IBaCC therefore represents a new, paraprobiotic One Health approach towards targeting Ascarididae that is safe, effective, massively scalable, stable, and useful in human and veterinary medicine in both the developed and developing regions of the world

A New Paraprobiotic-based Treatment for Control of Haemonchus Contortus in Sheep

Haemonchus contortus is a critical parasite of goats and sheep. Infection by this blood-feeding gastrointestinal nematode (GIN) parasite has significant health consequences, especially in lambs and kids. The parasite has developed resistance to virtually all known classes of small molecule anthelmintics used to treat it, giving rise in some areas to multidrug resistant parasites that are very difficult to control. Thus, new anthelmintics are urgently needed. Bacillus thuringiensis (Bt) crystal protein 5B (Cry5B), a naturally occurring protein made by a bacterium widely and safely used around the world as a bioinsecticide, represents a new non-small molecule modality for treating GINs. Cry5B has demonstrated anthelmintic activities against parasites of monogastric animals, including some related to those that infect humans, but has not yet been studied in a ruminant. Here we show that H. contortus adults are susceptible to Cry5B protein in vitro. Cry5B produced in its natural form as a spore-crystal lysate against H. contortus infections in goats had no significant efficacy. However, a new Active Pharmaceutical Ingredient (API) paraprobiotic form of Cry5B called IBaCC (Inactivated Bacterium with Cytosolic Crystals), in which Cry5B crystals are encapsulated in dead Bt cell wall ghosts, showed excellent efficacy in vitro against larval stages of H. contortus and relative protein stability in bovine rumen fluid. When given to sheep experimentally infected with H. contortus as three 60 mg/kg doses, Cry5B IBaCC resulted in significant reductions in fecal egg counts (90%) and parasite burdens (72%), with a very high impact on female parasites (96% reduction). These data indicate that Cry5B IBaCC is a potent new treatment tool for small ruminants in the battle against H. contortus

An inactivated bacterium (paraprobiotic) expressing Bacillus thuringiensis Cry5B as a therapeutic for Ascaris and Parascaris spp. infections in large animals

Ascaris and Parascaris are important parasites in the family Ascarididae, large, ubiquitous intestinal-dwelling nematodes infecting all classes of vertebrates. Parasitic nematode drug resistance in veterinary medicine and drug recalcitrance in human medicine are increasing worldwide, with few if any new therapeutic classes on the horizon. Some of these parasites are zoonotic, e.g., Ascaris is passed from humans to pigs and vice versa. The development of new therapies against this family of parasites would have major implications for both human and livestock health. Here we tested the therapeutic ability of a paraprobiotic or dead probiotic that expresses the Bacillus thuringiensis Cry5B protein with known anthelmintic properties, against zoonotic Ascaris suum and Parascaris spp. This paraprobiotic, known as IBaCC, intoxicated A. suum larvae in vitro and was highly effective in vivo against intestinal A. suum infections in a new mouse model for this parasite. Fermentation was scaled up to 350 l to treat pigs and horses. Single dose Cry5B IBaCC nearly completely cleared A. suum infections in pigs. Furthermore, single dose Cry5B IBaCC drove fecal egg counts in Parascaris-infected foals to zero, showing at least parity with, and potential superiority to, current efficacy of anthelmintics used against this parasite. Cry5B IBaCC therefore represents a new, paraprobiotic One Health approach towards targeting Ascarididae that is safe, effective, massively scalable, stable, and useful in human and veterinary medicine in both the developed and developing regions of the world