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Algorithm-Hardware Co-Optimization For Efficient High-Dimensional Computing

With the emergence of the Internet of Things (IoT), many applications run machine learning algorithms to perform cognitive tasks. The learning algorithms have been shown effectiveness for many tasks, e.g., object tracking, speech recognition, image classification, etc. However, since sensory and embedded devices are generating massive data streams, it poses huge technical challenges due to limited device resources. For example, although Deep Neural Networks (DNNs) such as AlexNet and GoogleNet have provided high classification accuracy for complex image classification tasks, their high computational complexity and memory requirement hinder usability to a broad variety of real-life (embedded) applications where the device resources and power budget is limited. Furthermore, in IoT systems, sending all the data to the powerful computing environment, e.g., cloud, cannot guarantee scalability and real-time response. It is also often undesirable due to privacy and security concerns. Thus, we need alternative computing methods that can run the large amount of data at least partly on the less-powerful IoT devices. Brain-inspired Hyperdimensional (HD) computing has been proposed as the alternative computing method that processes the cognitive tasks in a more light-weight way.  The HD computing is developed based on the fact that brains compute with patterns of neural activity which are not readily associated with numerical numbers. Recent research instead have utilized high dimension vectors (e.g., more than a thousand dimension), called hypervectors, to represent the neural activities, and showed successful progress for many cognitive tasks such as activity recognition, object recognition, language recognition, and bio-signal classification. 

Directed Pseudouridylation Of Cellular Rna Via Delivery Of Crispr/Cas And Esgrna Guide Combinations

resent strategies aimed to target and manipulate RNA in living cells mainly rely on the use of antisense oligonucleotides (ASO) or engineered RNA binding proteins (RBP). Although ASO therapies have been shown great promise in eliminating pathogenic transcripts or modulating RBP binding, they are synthetic in construction and thus cannot be encoded within DNA. This complicates potential gene therapy strategies, which would rely on regular administration of ASOs throughout the lifetime of the patient. Furthermore, they are incapable of modulating the genetic sequence of RNA. Although engineered RBPs such as PUF proteins can be designed to recognize target transcripts and fused to RNA modifying effectors to allow for specific recognition and manipulation, these constructs require extensive protein engineering for each target and may prove to be laborious and costly. Normal 0 false false false EN-US X-NONE X-NONE /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin-top:0in; mso-para-margin-right:0in; mso-para-margin-bottom:8.0pt; mso-para-margin-left:0in; line-height:107%; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri",sans-serif; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:"Times New Roman"; mso-bidi-theme-font:minor-bidi;}

Directed modification of cellular RNA via nuclear delivery of CRISPR/Cas

Present strategies aimed to target and manipulate RNA in living cells mainly rely on the use of antisense oligonucleotides (ASO) or engineered RNA binding proteins (RBP). Although ASO therapies have been shown great promise in eliminating pathogenic transcripts or modulating RBP binding, they are synthetic in construction and thus cannot be encoded within DNA. This complicates potential gene therapy strategies, which would rely on regular administration of ASOs throughout the lifetime of the patient. Furthermore, they are incapable of modulating the genetic sequence of RNA. Although engineered RBPs such as PUF proteins can be designed to recognize target transcripts and fused to RNA modifying effectors to allow for specific recognition and manipulation, these constructs require extensive protein engineering for each target and may prove to be laborious and costly. Normal 0 false false false EN-US X-NONE X-NONE /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin-top:0in; mso-para-margin-right:0in; mso-para-margin-bottom:8.0pt; mso-para-margin-left:0in; line-height:107%; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri",sans-serif; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:"Times New Roman"; mso-bidi-theme-font:minor-bidi;}

Collaborative High-Dimensional Computing

Internet of Things ( IoT ) applications often analyze collected data using machine learning algorithms. As the amount of the data keeps increasing, many applications send the data to powerful systems, e.g., data centers, to run the learning algorithms . On the one hand, sending the original data is not desirable due to privacy and security concerns.On the other hand, many machine learning models may require unencrypted ( plaintext ) data, e.g., original images , to train models and perform inference . When offloading theses computation tasks, sensitive information may be exposed to the untrustworthy cloud system which is susceptible to internal and external attacks . In many IoT systems , the learning procedure should be performed with the data that is held by a large number of user devices at the edge of Internet . These users may be unwilling to share the original data with the cloud and other users if security concerns cannot be addressed.

Targeted Identification Of Rna Bases That Hydrogen Bond With Protein

Normal 0 false false false EN-US X-NONE X-NONE /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin-top:0in; mso-para-margin-right:0in; mso-para-margin-bottom:8.0pt; mso-para-margin-left:0in; line-height:107%; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri",sans-serif; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:"Times New Roman"; mso-bidi-theme-font:minor-bidi;} RNA binding proteins are increasingly implicated in genetic and somatic diseases.  Higher resolution methods to identify their RNA targets and how the proteins may interact with specific bases within them are needed to develop drugs that interfere with the regulation or misregulation of RBPs via their binding sites.

Natural Killer Cells with Enhanced Activity (SD 2021-141)

NK cells possess a native ability to kill tumors and virally infected cells without prior antigen priming. Furthermore, NK cells can be administered to patients across HLA allotypes, unlike T cells which require HLA matching to avoid graft-versus-host disease. Many trials utilizing adoptive transfer of allogeneic NK cells demonstrated complete remissions in patients with acute myelogenous leukemia (AML) who are refractory to standard chemotherapy. Another recent clinical study demonstrated effective treatment of lymphoid malignancies using allogeneic CAR-expressing NK cells, with minimal side effects. Thus, NK cells possess a number of advantages over T cells that enables them to be used as safe, effective, “off-the-shelf” adoptive cell therapy product to treat diverse malignancies. Antibody-dependent cellular cytotoxicity (ADCC) is a key pathway that mediates natural killer (NK) cell cytotoxicity against antibody-opsonized target cells. This process helps mediate the therapeutic efficacy of anti-tumor antibodies. On NK cells, ADCC occurs via engagement of antibody-coated target cells with activating receptor leading to proinflammatory cytokine upregulation, degranulation, and target cell death. Upon cellular activation, the     is cleaved from the NK cell surface. Cleavage of the ectodomain prevents further antibody binding and signaling, which dampens NK cell activity. Blocking activation-induced cleavage has been previously demonstrated to augment ADCC activity and provides a novel strategy to improve efficacy of therapeutic antibodies in combination with adoptive transfer of engineered NK cells. 

Broad spectrum anti-cancer agents

One of the main problems in using immune checkpoint inhibitors (e.g. PD-L1/PD-1/PD-L2/CTLA4) as a cancer treatment is that there is a large percentage of patients (~60-70%) who do not respond to the treatment or become resistant to it. Researchers all over the world are looking for ways to increase response to immunotherapy in this large population of patients, such as identifying new signaling pathways and/or new targets involved in this process as well as identifying synthetic molecules that can modulate the functions of those pathways and targets.

Esophageal Deflection Device

Cardiac ablations are common medical treatments for people with atrial fibrillation (Afib). During the ablation procedure, a cardiac electrophysiologist will thermally ablate, or burn off, defective heart tissue with radiofrequency or cryoablation technology. The esophagus is often in close proximity to the left atrium. Since the left atrial tissue is approximately 2mm thin, the heat can transfer through it to the esophagus in contact and cause thermal damage / lesions on the esophagus.  In worst-case rare scenarios, an atrio-esophageal fistula, or hole between the esophagus and the heart, can occur which has a ~75% mortality rate.  It would be ideal to move the esophagus away from the heart before or during the ablation procedure preventing thermal damage.