Optimal sequential enrichment designs for phase II clinical trials

In the early phase development of molecularly targeted agents (MTAs), a commonly encountered situation is that the MTA is expected to be more effective for a certain biomarker subgroup, say marker-positive patients, but there is no adequate evidence to show that the MTA does not work for the other subgroup, that is, marker-negative patients. After establishing that marker-positive patients benefit from the treatment, it is often of great clinical interest to determine whether the treatment benefit extends to marker-negative patients. The authors propose optimal sequential enrichment (OSE) designs to address this practical issue in the context of phase II clinical trials. The OSE designs evaluate the treatment effect first in marker-positive patients and then in marker-negative patients if needed. The designs are optimal in the sense that they minimize the expected sample size or the maximum sample size under the null hypothesis that the MTA is futile. An efficient, accurate optimization algorithm is proposed to find the optimal design parameters. One important advantage of the OSE design is that the go/no-go interim decision rules are specified prior to the trial conduct, which makes the design particularly easy to use in practice. A simulation study shows that the OSE designs perform well and are ethically more desirable than the commonly used marker-stratified design. The OSE design is applied to an endometrial carcinoma trial

Parameter identification of BIPT system using chaotic-enhanced fruit fly optimization algorithm

Bidirectional inductive power transfer (BIPT) system facilitates contactless power transfer between two sides and across an air-gap, through weak magnetic coupling. Typically, this system is nonlinear high order system which includes nonlinear switch components and resonant networks, developing of accurate model is a challenging task. In this paper, a novel technique for parameter identification of a BIPT system is presented by using chaotic-enhanced fruit fly optimization algorithm (CFOA). The fruit fly optimization algorithm (FOA) is a new meta-heuristic technique based on the swarm behavior of the fruit fly. This paper proposes a novel CFOA, which employs chaotic sequence to enhance the global optimization capacity of original FOA. The parameter identification of the BIPT system is formalized as a multi-dimensional optimization problem, and an objective function is established minimizing the errors between the estimated and measured values. All the 11 parameters of this system (Lpi, LT, Lsi, Lso, CT, Cs, M, Rpi, RT, Rsi and Rso) can be identified simultaneously using measured input–output data. Simulations show that the proposed parameter identification technique is robust to measurements noise and variation of operation condition and thus it is suitable for practical application

Resistance-gene-directed discovery of a natural-product herbicide with a new mode of action.

Bioactive natural products have evolved to inhibit specific cellular targets and have served as lead molecules for health and agricultural applications for the past century1-3. The post-genomics era has brought a renaissance in the discovery of natural products using synthetic-biology tools4-6. However, compared to traditional bioactivity-guided approaches, genome mining of natural products with specific and potent biological activities remains challenging4. Here we present the discovery and validation of a potent herbicide that targets a critical metabolic enzyme that is required for plant survival. Our approach is based on the co-clustering of a self-resistance gene in the natural-product biosynthesis gene cluster7-9, which provides insight into the potential biological activity of the encoded compound. We targeted dihydroxy-acid dehydratase in the branched-chain amino acid biosynthetic pathway in plants; the last step in this pathway is often targeted for herbicide development10. We show that the fungal sesquiterpenoid aspterric acid, which was discovered using the method described above, is a sub-micromolar inhibitor of dihydroxy-acid dehydratase that is effective as a herbicide in spray applications. The self-resistance gene astD was validated to be insensitive to aspterric acid and was deployed as a transgene in the establishment of plants that are resistant to aspterric acid. This herbicide-resistance gene combination complements the urgent ongoing efforts to overcome weed resistance11. Our discovery demonstrates the potential of using a resistance-gene-directed approach in the discovery of bioactive natural products

KPNet: Towards Minimal Face Detector

The small receptive field and capacity of minimal neural networks limit their performance when using them to be the backbone of detectors. In this work, we find that the appearance feature of a generic face is discriminative enough for a tiny and shallow neural network to verify from the background. And the essential barriers behind us are 1) the vague definition of the face bounding box and 2) tricky design of anchor-boxes or receptive field. Unlike most top-down methods for joint face detection and alignment, the proposed KPNet detects small facial keypoints instead of the whole face by in a bottom-up manner. It first predicts the facial landmarks from a low-resolution image via the well-designed fine-grained scale approximation and scale adaptive soft-argmax operator. Finally, the precise face bounding boxes, no matter how we define it, can be inferred from the keypoints. Without any complex head architecture or meticulous network designing, the KPNet achieves state-of-the-art accuracy on generic face detection and alignment benchmarks with only $\sim1M$ parameters, which runs at 1000fps on GPU and is easy to perform real-time on most modern front-end chips.Comment: AAAI 202

COMCAT: Towards Efficient Compression and Customization of Attention-Based Vision Models

Attention-based vision models, such as Vision Transformer (ViT) and its variants, have shown promising performance in various computer vision tasks. However, these emerging architectures suffer from large model sizes and high computational costs, calling for efficient model compression solutions. To date, pruning ViTs has been well studied, while other compression strategies that have been widely applied in CNN compression, e.g., model factorization, is little explored in the context of ViT compression. This paper explores an efficient method for compressing vision transformers to enrich the toolset for obtaining compact attention-based vision models. Based on the new insight on the multi-head attention layer, we develop a highly efficient ViT compression solution, which outperforms the state-of-the-art pruning methods. For compressing DeiT-small and DeiT-base models on ImageNet, our proposed approach can achieve 0.45% and 0.76% higher top-1 accuracy even with fewer parameters. Our finding can also be applied to improve the customization efficiency of text-to-image diffusion models, with much faster training (up to $2.6\times$ speedup) and lower extra storage cost (up to $1927.5\times$ reduction) than the existing works.Comment: ICML 2023 Poste

(25R)-5a-Spiro­stane-3,12-dione

The title compound, C27H40O4, was obtained from the oxidation of (25R)-3b-hydr­oxy-5a-spiro­stan-12-one (Hecogenin) by Jone’s reagent. The mol­ecule contains six alicyclic and heterocyclic rings, all trans-fused, among which four six-membered rings adopt similar chair conformations while two five-membered rings assume an envelope conformation