All computational procedures were performed either on a desktop workstation running Ubuntu 18.04 By minimising off-target activation, Bayesian target optimisation could enable (e.g.) Here we provide further mathematical details for optimising holographic stimuli. Next we must evaluate the partial derivative on the right-hand side of Equation 13. The covariance between a GP and its derivative is given by [40, Sec 9.4] Simulations consisted of both ORF mapping and stimulus optimisation phases. For reference, a typical ORF mean function is given in Figure S2.

In this work, we address both of the above issues.

Two-photon optogenetics has transformed our ability to probe the structure and function of neural circuits.

Motivation: Codon optimization of Open Reading Frame (ORF) sequences is essential for enhancing mRNA stability and expression in applications like mRNA vaccines, where codon choice can significantly impact protein yield which directly impacts immune strength. In this work, we investigate the use of a pre-trained protein language model (PPLM) for getting a rich representation of amino acids which could be utilized for codon optimization. This leaves us with a simpler fine-tuning task over PPLM in optimizing ORF sequences. Results: The ORFs generated by our proposed models outperformed their natural counterparts encoding the same proteins on computational metrics for stability and expression. They also demonstrated enhanced performance against the benchmark ORFs used in mRNA vaccines for the SARS-CoV-2 viral spike protein and the varicella-zoster virus (VZV). These results highlight the potential of adapting PPLM for designing ORFs tailored to encode target antigens in mRNA vaccines.

We present an intriguing discovery related to Random Fourier Features: in Gaussian kernel approximation, replacing the random Gaussian matrix by a properly scaled random orthogonal matrix significantly decreases kernel approximation error. We call this technique Orthogonal Random Features (ORF), and provide theoretical and empirical justification for this behavior. Motivated by this discovery, we further propose Structured Orthogonal Random Features (SORF), which uses a class of structured discrete orthogonal matrices to speed up the computation.

This paper reports on a set of three recent experiments utilizing large-scale speech models to evaluate the oral reading fluency (ORF) of students in Ghana. While ORF is a well-established measure of foundational literacy, assessing it typically requires one-on-one sessions between a student and a trained evaluator, a process that is time-consuming and costly. Automating the evaluation of ORF could support better literacy instruction, particularly in education contexts where formative assessment is uncommon due to large class sizes and limited resources. To our knowledge, this research is among the first to examine the use of the most recent versions of large-scale speech models (Whisper V2 wav2vec2.0) for ORF assessment in the Global South. We find that Whisper V2 produces transcriptions of Ghanaian students reading aloud with a Word Error Rate of 13.5. This is close to the model's average WER on adult speech (12.8) and would have been considered state-of-the-art for children's speech transcription only a few years ago. We also find that when these transcriptions are used to produce fully automated ORF scores, they closely align with scores generated by expert human graders, with a correlation coefficient of 0.96. Importantly, these results were achieved on a representative dataset (i.e., students with regional accents, recordings taken in actual classrooms), using a free and publicly available speech model out of the box (i.e., no fine-tuning). This suggests that using large-scale speech models to assess ORF may be feasible to implement and scale in lower-resource, linguistically diverse educational contexts.

Random features have been introduced to scale up kernel methods via randomization techniques. In particular, random Fourier features and orthogonal random features were used to approximate the popular Gaussian kernel. The former is performed by a random Gaussian matrix and leads exactly to the Gaussian kernel after averaging. In this work, we analyze the bias and the variance of the kernel approximation based on orthogonal random features which makes use of Haar orthogonal matrices. We provide explicit expressions for these quantities using normalized Bessel functions and derive sharp exponential bounds supporting the view that orthogonal random features are more informative than random Fourier features.

We present Simplex Random Features (SimRFs), a new random feature (RF) mechanism for unbiased approximation of the softmax and Gaussian kernels by geometrical correlation of random projection vectors. We prove that SimRFs provide the smallest possible mean square error (MSE) on unbiased estimates of these kernels among the class of weight-independent geometrically-coupled positive random feature (PRF) mechanisms, substantially outperforming the previously most accurate Orthogonal Random Features at no observable extra cost. We present a more computationally expensive SimRFs+ variant, which we prove is asymptotically optimal in the broader family of weight-dependent geometrical coupling schemes (which permit correlations between random vector directions and norms). In extensive empirical studies, we show consistent gains provided by SimRFs in settings including pointwise kernel estimation, nonparametric classification and scalable Transformers.