No abstract

How do neural language models keep track of number agreement between subject and verb? We show that 'diagnostic classifiers', trained to predict number from the internal states of a language model, provide a detailed understanding of how, when, and where this information is represented. Moreover, they give us insight into when and where number information is corrupted in cases where the language model ends up making agreement errors. To demonstrate the causal role played by the representations we find, we then use agreement information to influence the course of the LSTM during the processing of difficult sentences. Results from such an intervention reveal a large increase in the language model's accuracy. Together, these results show that diagnostic classifiers give us an unrivalled detailed look into the representation of linguistic information in neural models, and demonstrate that this knowledge can be used to improve their performance.

Immobilization of metal-organic frameworks (MOFs) onto flexible polymeric substrates as secondary supports expands the versatility of MOFs for surface coatings for the development of functional materials. In this work, we demonstrate the deposition of copper(II) benzene-1,3,5-tricarboxylate (CuBTC) crystals directly onto the surface of carboxyl-functionalized cotton capable of generating the therapeutic bioagent nitric oxide (NO) from endogenous sources. Characterization of the CuBTC-cotton material by XRD, ATR-IR, and UV-vis indicate that CuBTC is successfully immobilized on the cotton fabric. In addition, SEM imaging reveals excellent surface coverage with well-defined CuBTC crystals. Subsequently, the CuBTC-cotton material was evaluated as a supported heterogeneous catalyst for the generation of NO using S-nitrosocysteamine as the substrate. The resulting reactivity is consistent with the activity observed for unsupported CuBTC particles. Overall, this work demonstrates deposition of MOFs onto a flexible polymeric material with excellent coverage as well as catalytic NO release from S-nitrosocysteamine at therapeutic levels.

The versatile chemical and physical properties of metal organic frameworks (MOFs) have made them unique platforms for the design of biomimetic catalysts, but with only limited success to date due to instability of the MOFs employed in physiological environments. Herein, the use of Cu(II)1,3,5-Benzene-tris-triazole (CuBTTri) is demonstrated for the catalytic generation of the bioactive agent nitric oxide (NO) from endogenous sources, S -nitrosothiols (RSNOs). CuBTTri exhibits structural integrity in aqueous environments, including phosphate buffered saline (76 h, pH 7.4, 37 °C), cell media used for in vitro testing (76 h, pH 7.4, 37 °C), and fresh citrated whole blood (30 min, pH 7.4, 37 °C). The application of CuBTTri for use in polymeric medical devices is explored through the formation of a composite CuBTTripoly by blending CuBTTri into biomedical grade polyurethane matrices. Once prepared, the CuBTTri-poly material retains the catalytic function towards the generation of NO with tunable release kinetics proportional to the total content of CuBTTri embedded into the polymeric material with a surface fl ux corresponding to the therapeutic range of 1-100 n M cm −2 min −1 , which is maintained even following exposure to blood.

The use of metal organic frameworks (MOFs) for the catalytic production of nitric oxide (NO) is reported. In this account we demonstrate the use of Cu(3)(BTC)(2) as a catalyst for the generation of NO from the biologically occurring substrate, S-nitrosocysteine (CysNO). The MOF catalyst was evaluated as an NO generator by monitoring the evolution of NO in real time via chemiluminescence. The addition of 2, 10, and 15-fold excess CysNO to MOF-Cu(II) sites and cysteine (CysH) resulted in catalytic turnover of the active sites and nearly 100% theoretical yield of the NO product. Control experiments without the MOF present did not yield appreciable NO generation. In separate studies the MOF was found to be reusable over successive iterations of CysNO additions without loss of activity. Subsequently, the MOF catalyst was confirmed to remain structurally intact by pXRD and ATR-IR following reaction with CysNO and CysH.

No abstract

Coding a wide range of light intensities in natural scenes poses a challenge for the retina: adaptation to bright light should not compromise sensitivity to dim light. Here we report a novel form of activity-dependent synaptic plasticity, specifically, a "weighted potentiation" that selectively increases output of Mb-type bipolar cells in the goldfish retina in response to weak inputs but leaves the input-output ratio for strong stimuli unaffected. In retinal slice preparation, strong depolarization of bipolar terminals significantly lowered the threshold for calcium spike initiation, which originated from a shift in activation of voltage-gated calcium currents (I Ca ) to more negative potentials. The process depended upon glutamate-evoked retrograde nitric oxide (NO) signaling as it was eliminated by pretreatment with an NO synthase blocker, TRIM. The NO-dependent I Ca modulation was cGMP independent but could be blocked by N-ethylmaleimide (

Nitric oxide (NO) is an essential messenger in human physiology, mediating cellular processes ranging from proliferation to apoptosis. The effects of NO are concentration dependent, and control over the instantaneous amount of NO available to cells is essential for determining the therapeutic NO dosages for various applications. As such, the development of NO therapeutic materials relies on accurate quantitative NO measurements that provide both total NO release from the NO donor as well as instantaneous NO concentrations. On the basis of the complexity of the cell media environment, inaccurate NO reporting often occurs for in vitro studies. These inaccuracies result from using inert media such as phosphate buffer saline (PBS), failing to account for the reactivity of media components. In this work, we describe a method for directly quantifying the instantaneous and total amounts of NO from commonly used NO donors in commercially available cell media routinely used for endothelial and neural cell lines. A riboflavin-tryptophan complex found in the media was identified as the major scavenger of NO in the cell media and likely reacts with NO via a radical-radical reaction. This finding significantly impacts the amount of available NO. The scavenging effects are concentration dependent on the riboflavin-tryptophan complex and the NO release rate from the NO donor. The results of this study provide insights on the exogenous amounts of NO that are present in cell media and may provide an explanation for differences in NO dosages between buffer experiments and in vitro and in vivo studies.