Efficient Sharpness-aware Minimization for Improved Training of Neural Networks

Overparametrized Deep Neural Networks (DNNs) often achieve astounding performances, but may potentially result in severe generalization error. Recently, the relation between the sharpness of the loss landscape and the generalization error has been established by Foret et al. (2020), in which the Sharpness Aware Minimizer (SAM) was proposed to mitigate the degradation of the generalization. Unfortunately, SAM s computational cost is roughly double that of base optimizers, such as Stochastic Gradient Descent (SGD). This paper thus proposes Efficient Sharpness Aware Minimizer (ESAM), which boosts SAM s efficiency at no cost to its generalization performance. ESAM includes two novel and efficient training strategies-StochasticWeight Perturbation and Sharpness-Sensitive Data Selection. In the former, the sharpness measure is approximated by perturbing a stochastically chosen set of weights in each iteration; in the latter, the SAM loss is optimized using only a judiciously selected subset of data that is sensitive to the sharpness. We provide theoretical explanations as to why these strategies perform well. We also show, via extensive experiments on the CIFAR and ImageNet datasets, that ESAM enhances the efficiency over SAM from requiring 100% extra computations to 40% vis-a-vis base optimizers, while test accuracies are preserved or even improved

Performance of Noninvasive Tests of Fibrosis Among Asians, Hispanic, and non-Hispanic Whites in the STELLAR Trials

BACKGROUND & AIMS: The effect of race on routinely available noninvasive tests of fibrosis is incompletely under stood. This study evaluated the performance of noninvasive tests among white and Asian pa tients in the STELLAR trials (NCT03053050 and NCT03053063), which evaluated selonsertib in patients with advanced (F3-F4) fibrosis due to nonalcoholic steatohepatitis (NASH). METHODS: Baseline liver biopsies were centrally read using the NASH Clinical Research Network system, and 4 noninvasive tests (Nonalcoholic fatty liver disease fibrosis score [NFS], Fibrosis-4 index [FIB-4], Enhanced Liver Fibrosis test [ELF], and liver stiffness by vibration-controlled transient elastography) were measured. The performance of these tests to discriminate advanced fibrosis was evaluated using areas under the receiver operating characteristics curves with 5-fold cross validation repeated 100 times. RESULTS: Among 3207 patients screened with evaluable liver histology, 2281 were whites and 762 were Asians. Seventy-two percent of whites and 67% of Asians had advanced fibrosis. The areas under the receiver operating characteristics curves of the noninvasive tests for advanced fibrosis were similar in whites and Asians: 0.73 and 0.75 for NFS, 0.78 and 0.80 for FIB-4, 0.79 and 0.81 for ELF, and 0.80 and 0.83 for liver stiffness, respectively. At the published cutoffs, the tests had similar sensitivities and specificities in the 2 groups. However, the sensitivities of NFS, FIB-4, and ELF were low in both white and Asian patients younger than 40 years. CONCLUSIONS: In the global phase III STELLAR trials, the diagnostic performance of routinely available noninvasive tests for the detection of advanced fibrosis due to NASH was acceptable and similar between white and Asian patients

Primary sclerosing lipogranuloma: an unusual scrotal mass

Sclerosing lipogranuloma (SLG) of the male external genitalia is a rare benign condition presenting as subcutaneous masses. The underlying pathological process is a granulomatous reaction of fatty tissue in this area. The cause of this is unclear but hypothesis stems around the pathogenesis of exogenous lipid degeneration from injection of foreign bodies such as paraffin for penile augmentation. However, endogenous lipid degeneration from other various causes such as infection, trauma, and allergic mechanisms has also been reported. We present the case of a 40-year-old man with primary SLG of the external genitalia. Literature review on the treatment strategies are addressed and discussed

Teixobactin analogues reveal enduracididine to be non-essential for highly potent antibacterial activity and lipid II binding

Abstract. Teixobactin is a highly promising antibacterial depsipeptide consisting of four D-amino acids and a rare L-allo-enduracididine amino acid. L-allo-enduracididine is reported to be important for the highly potent antibacterial activity of teixobactin. However, it is also a key limiting factor in the development of potent teixobactin analogues due to several synthetic challenges such as it is not commercially available, requires a multistep synthesis, long and repititive couplings (16-30 hours). Due to all these challenges, the total synthesis of teixobactin is laborious and low yielding (3.3%). In this work, we have identified a unique design and developed a rapid synthesis (10 min μwave assisted coupling per amino acid, 30 min cyclisation) of several highly potent analogues of teixobactin with yields of 10-24% by replacing the L-allo-enduracididine with commercially available non-polar residues such as leucine and isoleucine. Most importantly, the Leu10-teixobactin and Ile10-teixobactin analogues have shown highly potent antibacterial activity against a broader panel of MRSA and Enterococcus faecalis (VRE). Time-kill kinetics data indicate that both these compounds are superior to vancomycin against MRSA (16 times more potent). Furthermore, these synthetic analogues displayed identical antibacterial activity to natural teixobactin (MIC 0.25 μg/ml) against MRSA ATCC 33591 despite their simpler design and ease of synthesis. Detailed NMR analyses have provided us with further insight into the 3D structures of these important analogues. We have confirmed lipid II binding and measured the binding affinities of individual amino acid residues of Ala10-teixobactin towards geranyl pyrophosphate (a lipid II mimic) by NMR to understand the nature and strength of binding interactions of the amino acid residues. An antagonization assay further confirms a lipid II mediated mode of action. Contrary to current understanding, we have shown that a cationic amino acid at position 10 is not essential for target (lipid II) binding and potent antibacterial activity of teixobactin. We thus provide strong evidence contrary to the many assumptions made about the mechanism of action of this exciting new antibiotic. Introduction of a non-cationic residue at position 10 allows for tremendous diversification in terms of the design and synthesis of highly potent teixobactin analogues and lays the foundations for the development of teixobactin analogues as new drug-like molecules to target MRSA and Mycobacterium tuberculosis

Improving bus service reliability: The Singapore experience

In February 2014, Singapore embarked on a 2-year trial of a Bus Service Reliability Framework (BSRF) to improve en-route bus regularity and reduce instances of bus bunching and prolonged waiting times. Based on London's Quality Incentive Contract, the Singapore model also imposes penalties or provides incentives to operators for increases/reductions of Excess Wait Time (EWT) beyond a certain route-specific baseline. Drawing on insights derived from research on performance-based contracts, this paper describes some key considerations surrounding this particular innovation in Singapore's overall bus regulatory framework. We also discuss an important advancement in our understanding of how bus users value reliability improvements through estimates obtained from stated preference data. At the same time, early indications from the trial have been encouraging

Possibility of Segaliud Lokan Forest Reserve (SLFR), Sandakan As Nature Tourism Attraction

The tourism sector in Sabah is rapidly developing as the state has high biodiversity resources. The state needs to diversify its natural tourism destinations to increase the number of tourists because tourism is one of the sector that give some contribution to the economic state. Segaliud Lokan Forest Reserve which located in Sandakan district is a newly discovered conservation area that has the potential to be a natural tourism area as this area is rich in biodiversity of flora and fauna as well as attractive landscapes. The objective of the study is to identify the natural resources found in the SLFR that can be the tourist attraction. The Criteria for Assessing Natural Tourism Potential based on National Ecotourism Plan of Malaysia (Guideline for Sabah State) was used in this study. This study shows that the SLFR area has the potential to be a nature tourism attraction but recommends to have some management mechanism in place to precede any development of tourism activity