Determining the Quantitative Principles of T Cell Response to Antigenic Disparity in Stem Cell Transplantation

Alloreactivity compromising clinical outcomes in stem cell transplantation is observed despite HLA matching of donors and recipients. This has its origin in the variation between the exomes of the two, which provides the basis for minor histocompatibility antigens (mHA). The mHA presented on the HLA class I and II molecules and the ensuing T cell response to these antigens results in graft vs. host disease. In this paper, results of a whole exome sequencing study are presented, with resulting alloreactive polymorphic peptides and their HLA class I and HLA class II (DRB1) binding affinity quantified. Large libraries of potentially alloreactive recipient peptides binding both sets of molecules were identified, with HLA-DRB1 generally presenting a greater number of peptides. These results are used to develop a quantitative framework to understand the immunobiology of transplantation. A tensor-based approach is used to derive the equations needed to determine the alloreactive donor T cell response from the mHA-HLA binding affinity and protein expression data. This approach may be used in future studies to simulate the magnitude of expected donor T cell response and determine the risk for alloreactive complications in HLA matched or mismatched hematopoietic cell and solid organ transplantation

One-To-Many Multilingual End-to-end Speech Translation

Nowadays, training end-to-end neural models for spoken language translation (SLT) still has to confront with extreme data scarcity conditions. The existing SLT parallel corpora are indeed orders of magnitude smaller than those available for the closely related tasks of automatic speech recognition (ASR) and machine translation (MT), which usually comprise tens of millions of instances. To cope with data paucity, in this paper we explore the effectiveness of transfer learning in end-to-end SLT by presenting a multilingual approach to the task. Multilingual solutions are widely studied in MT and usually rely on ``\textit{target forcing}'', in which multilingual parallel data are combined to train a single model by prepending to the input sequences a language token that specifies the target language. However, when tested in speech translation, our experiments show that MT-like \textit{target forcing}, used as is, is not effective in discriminating among the target languages. Thus, we propose a variant that uses target-language embeddings to shift the input representations in different portions of the space according to the language, so to better support the production of output in the desired target language. Our experiments on end-to-end SLT from English into six languages show important improvements when translating into similar languages, especially when these are supported by scarce data. Further improvements are obtained when using English ASR data as an additional language (up to $+2.5$ BLEU points).Comment: 8 pages, one figure, version accepted at ASRU 201

Transformer-based NMT : modeling, training and implementation

International trade and industrial collaborations enable countries and regions to concentrate their developments on specific industries while making the most of other countries' specializations, which significantly accelerates global development. However, globalization also increases the demand for cross-region communication. Language barriers between many languages worldwide create a challenge for achieving deep collaboration between groups speaking different languages, increasing the need for translation. Language technology, specifically, Machine Translation (MT) holds the promise to enable communication between languages efficiently in real-time with minimal costs. Even though nowadays computers can perform computation in parallel very fast, which provides machine translation users with translations with very low latency, and although the evolution from Statistical Machine Translation (SMT) to Neural Machine Translation (NMT) with the utilization of advanced deep learning algorithms has significantly boosted translation quality, current machine translation algorithms are still far from accurately translating all input. Thus, how to further improve the performance of state-of-the-art NMT algorithm remains a valuable open research question which has received a wide range of attention. In the research presented in this thesis, we first investigate the long-distance relation modeling ability of the state-of-the-art NMT model, the Transformer. We propose to learn source phrase representations and incorporate them into the Transformer translation model, aiming to enhance its ability to capture long-distance dependencies well. Second, though previous work (Bapna et al., 2018) suggests that deep Transformers have difficulty in converging, we empirically find that the convergence of deep Transformers depends on the interaction between the layer normalization and residual connections employed to stabilize its training. We conduct a theoretical study about how to ensure the convergence of Transformers, especially for deep Transformers, and propose to ensure the convergence of deep Transformers by putting the Lipschitz constraint on its parameter initialization. Finally, we investigate how to dynamically determine proper and efficient batch sizes during the training of the Transformer model. We find that the gradient direction gets stabilized with increasing batch size during gradient accumulation. Thus we propose to dynamically adjust batch sizes during training by monitoring the gradient direction change within gradient accumulation, and to achieve a proper and efficient batch size by stopping the gradient accumulation when the gradient direction starts to fluctuate. For our research in this thesis, we also implement our own NMT toolkit, the Neutron implementation of the Transformer and its variants. In addition to providing fundamental features as the basis of our implementations for the approaches presented in this thesis, we support many advanced features from recent cutting-edge research work. Implementations of all our approaches in this thesis are also included and open-sourced in the toolkit. To compare with previous approaches, we mainly conducted our experiments on the data from the WMT 14 English to German (En-De) and English to French (En-Fr) news translation tasks, except when studying the convergence of deep Transformers, where we alternated the WMT 14 En-Fr task with the WMT 15 Czech to English (Cs-En) news translation task to compare with Bapna et al. (2018). The sizes of these datasets vary from medium (the WMT 14 En-De, ~ 4.5M sentence pairs) to very large (the WMT 14 En-Fr, ~ 36M sentence pairs), thus we suggest our approaches help improve the translation quality between popular language pairs which are widely used and have sufficient data.China Scholarship Counci