Interpretable and Steerable Sequence Learning via Prototypes

One of the major challenges in machine learning nowadays is to provide predictions with not only high accuracy but also user-friendly explanations. Although in recent years we have witnessed increasingly popular use of deep neural networks for sequence modeling, it is still challenging to explain the rationales behind the model outputs, which is essential for building trust and supporting the domain experts to validate, critique and refine the model. We propose ProSeNet, an interpretable and steerable deep sequence model with natural explanations derived from case-based reasoning. The prediction is obtained by comparing the inputs to a few prototypes, which are exemplar cases in the problem domain. For better interpretability, we define several criteria for constructing the prototypes, including simplicity, diversity, and sparsity and propose the learning objective and the optimization procedure. ProSeNet also provides a user-friendly approach to model steering: domain experts without any knowledge on the underlying model or parameters can easily incorporate their intuition and experience by manually refining the prototypes. We conduct experiments on a wide range of real-world applications, including predictive diagnostics for automobiles, ECG, and protein sequence classification and sentiment analysis on texts. The result shows that ProSeNet can achieve accuracy on par with state-of-the-art deep learning models. We also evaluate the interpretability of the results with concrete case studies. Finally, through user study on Amazon Mechanical Turk (MTurk), we demonstrate that the model selects high-quality prototypes which align well with human knowledge and can be interactively refined for better interpretability without loss of performance.Comment: Accepted as a full paper at KDD 2019 on May 8, 201

Novel zinc-based fixative for high quality DNA, RNA and protein analysis

We have developed a reliable, cost-effective and non-toxic fixative to meet the needs of contemporary molecular pathobiology research, particularly in respect of RNA and DNA integrity. The effects of 25 different fixative recipes on the fixed quality of tissues from C57BL/6 mice were investigated. Results from IHC, PCR, RT–PCR, RNA Agilent Bioanalyser and Real-Time PCR showed that a novel zinc-based fixative (Z7) containing zinc trifluoroacetate, zinc chloride and calcium acetate was significantly better than the standard zinc-based fixative (Z2) and neutral buffered formalin (NBF) for DNA, RNA and protein preservation. DNA sequences up to 2.4 kb in length and RNA fragments up to 361 bp in length were successfully amplified from Z7 fixed tissues, as demonstrated by PCR, RT–PCR and Real-Time PCR. Total protein analysis was achieved using 2-D gel electrophoresis. In addition, nucleic acids and proteins were very stable over a 6–14-month period. This improved, non-toxic and economical tissue fixative could be applied for routine use in pathology laboratories to permit subsequent genomic/proteomic studies

DIP/WISH deficiency enhances synaptic function and performance in the Barnes maze

<p>Abstract</p> <p>Background</p> <p>DIP (diaphanous interacting protein)/WISH (WASP interacting SH3 protein) is a protein involved in cytoskeletal signaling which regulates actin cytoskeleton dynamics and/or microtubules mainly through the activity of Rho-related proteins. Although it is well established that: 1) spine-head volumes change dynamically and reflect the strength of the synapse accompanying long-term functional plasticity of glutamatergic synaptic transmission and 2) actin organization is critically involved in spine formation, the involvement of DIP/WISH in these processes is unknown.</p> <p>Results</p> <p>We found that DIP/WISH-deficient hippocampal CA1 neurons exhibit enhanced long-term potentiation via modulation of both pre- and post-synaptic events. Consistent with these electrophysiological findings, DIP/WISH-deficient mice, particularly at a relatively young age, found the escape hole more rapidly in the Barnes maze test.</p> <p>Conclusions</p> <p>We conclude that DIP/WISH deletion improves performance in the Barnes maze test in mice probably through increased hippocampal long-term potentiation.</p

Highly Sensitive Fluorescence Probe Based on Functional SBA-15 for Selective Detection of Hg2+

An inorganic–organic hybrid fluorescence chemosensor (DA/SBA-15) was prepared by covalent immobilization of a dansylamide derivative into the channels of mesoporous silica material SBA-15 via (3-aminopropyl)triethoxysilane (APTES) groups. The primary hexagonally ordered mesoporous structure of SBA-15 was preserved after the grafting procedure. Fluorescence characterization shows that the obtained inorganic–organic hybrid composite is highly selective and sensitive to Hg2+ detection, suggesting the possibility for real-time qualitative or quantitative detection of Hg2+ and the convenience for potential application in toxicology and environmental science

Synthesis of Zinc Phosphonated Poly(ethylene imine) and Its Fire-Retardant Effect in Low-Density Polyethylene

A novel oligomeric intumescent fire-retardant chelate, zinc phosphonated poly(ethylene imine) (Zn-PEIP), with a variable Zn2+ loading, was synthesized. The chemical structure of Zn-PEIP was confirmed by FTIR, 13C NMR, and 31P NMR spectroscopies. The thermal behavior and fire retardancy of low-density polyethylene (LDPE) containing 25 wt % Zn-PEIPs with different amounts of Zn2+ were investigated by thermogravimetric analysis (TGA), limiting oxygen index (LOI) measurements, and cone calorimetry. The TGA results showed that higher concentrations of Zn2+ improved the thermal stability and increased the residue yield of LDPE. However, the data from the LOI and cone calorimetry tests showed that there is an optimum concentration of Zn2+ for the best fire-retardancy performance of LDPE. This behavior is ascribed to the high cross-link density resulting from zinc bridges, preventing normal swelling of the intumescent system. The surface morphology of the char was characterized by digital photography and scanning electron microscopy (SEM). This confirmed the optimum intumescence and coherent and strong barrier layer formation at an intermediate Zn2+ loading

Ca2+ Permeable AMPA Receptor Induced Long-Term Potentiation Requires PI3/MAP Kinases but Not Ca/CaM-Dependent Kinase II

Ca2+ influx via GluR2-lacking Ca2+-permeable AMPA glutamate receptors (CP-AMPARs) can trigger changes in synaptic efficacy in both interneurons and principle neurons, but the underlying mechanisms remain unknown. We took advantage of genetically altered mice with no or reduced GluR2, thus allowing the expression of synaptic CP-AMPARs, to investigate the molecular signaling process during CP-AMPAR-induced synaptic plasticity at CA1 synapses in the hippocampus. Utilizing electrophysiological techniques, we demonstrated that these receptors were capable of inducing numerous forms of long-term potentiation (referred to as CP-AMPAR dependent LTP) through a number of different induction protocols, including high-frequency stimulation (HFS) and theta-burst stimulation (TBS). This included a previously undemonstrated form of protein-synthesis dependent late-LTP (L-LTP) at CA1 synapses that is NMDA-receptor independent. This form of plasticity was completely blocked by the selective CP-AMPAR inhibitor IEM-1460, and found to be dependent on postsynaptic Ca2+ ions through calcium chelator (BAPTA) studies. Surprisingly, Ca/CaM-dependent kinase II (CaMKII), the key protein kinase that is indispensable for NMDA-receptor dependent LTP at CA1 synapses appeared to be not required for the induction of CP-AMPAR dependent LTP due to the lack of effect of two separate pharmacological inhibitors (KN-62 and staurosporine) on this form of potentiation. Both KN-62 and staurosporine strongly inhibited NMDA-receptor dependent LTP in control studies. In contrast, inhibitors for PI3-kinase (LY294002 and wortmannin) or the MAPK cascade (PD98059 and U0126) significantly attenuated this CP-AMPAR-dependent LTP. Similarly, postsynaptic infusion of tetanus toxin (TeTx) light chain, an inhibitor of exocytosis, also had a significant inhibitory effect on this form of LTP. These results suggest that distinct synaptic signaling underlies GluR2-lacking CP-AMPAR-dependent LTP, and reinforces the recent notions that CP-AMPARs are important facilitators of synaptic plasticity in the brain