Miracle-dz/UniFAR-FTUs huggingface dataset:
A Geometric Perspective on the Transferability of Adversarial Directions

State-of-the-art machine learning models frequently misclassify inputs that have been perturbed in an adversarial manner. Adversarial perturbations generated for a given input and a specific classifier often seem to be effective on other inputs and even different classifiers. In other words, adversarial perturbations seem to transfer between different inputs, models, and even different neural network architectures. In this work, we show that in the context of linear classifiers and two-layer ReLU networks, there provably exist directions that give rise to adversarial perturbations for many classifiers and data points simultaneously. We show that these "transferable adversarial directions" are guaranteed to exist for linear separators of a given set, and will exist with high probability for linear classifiers trained on independent sets drawn from the same distribution. We extend our results to large classes of two-layer ReLU networks. We further show that adversarial directions for ReLU networks transfer to linear classifiers while the reverse need not hold, suggesting that adversarial perturbations for more complex models are more likely to transfer to other classifiers. We validate our findings empirically, even for deeper ReLU networks.
Assessment of the American College of Radiology Thyroid Imaging Reporting and Data System for Thyroid Nodule Malignancy Risk Stratification in a Pediatric Population.

OBJECTIVE The purpose of this study is to assess the diagnostic performance of the American College of Radiology (ACR) Thyroid Imaging Reporting and Data System (TIRADS) for malignancy risk in pediatric thyroid nodules. MATERIALS AND METHODS Two radiologists reviewed ultrasound images of 74 tissue-proven thyroid nodules in 62 children. Points were given for individual features and then added to determine the ACR TI-RADS category, ranging from 1 (benign) to 5 (high suspicion). Kappa coefficients were generated to assess intra- and interobserver agreement. Generalized linear mixed-effects models were used to estimate the odds of malignancy with construction of a supplementary ROC curve. RESULTS Fifty-four nodules were benign and 20 were malignant, with a median ACR TI-RADS category of 4 (interquartile range, 4-5). Nineteen of 20 (95.0%) malignant nodules were rated as TI-RADS category 4 or 5. There was substantial intraobserver agreement (κ = 0.69-0.77; p < 0.001) and moderate interobserver agreement (κ = 0.37; p = 0.002) for TIRADS category. Univariable analysis showed that, with every 1-unit increase of TI-RADS category, the likelihood of malignancy increased 2.63 times (95% CI, 1.08-6.41; p = 0.03). After adjusting for nodule size, TI-RADS category remained marginally associated with malignancy (adjusted odds ratio, 2.27; 95% CI, 0.93-5.54; p = 0.07). The AUC was 0.75 (95% CI, 0.64-0.86). An optimal cut point of TI-RADS category 5 was selected, with TI-RADS category 5 nodules 10.44 times (95% CI, 2.71-40.21; p < 0.0001) more likely than categories 1-4 nodules to be malignant. CONCLUSION ACR TI-RADS discriminates well between malignant and benign nodules in a pediatric population, particularly at TI-RADS category 5.
Fermentative Production of N-Methylglutamate From Glycerol by Recombinant Pseudomonas putida

N-methylated amino acids are present in diverse biological molecules in bacteria, archaea and eukaryotes. There is an increasing interest in this molecular class of alkylated amino acids by the pharmaceutical and chemical industries. N-alkylated amino acids have desired functions such as higher proteolytic stability, enhanced membrane permeability and longer peptide half-lives, which are important for the peptide-based drugs, the so-called peptidomimetics. Chemical synthesis of N-methylated amino acids often is limited by incomplete stereoselectivity, over-alkylation or the use of hazardous chemicals. Here, we describe metabolic engineering of Pseudomonas putida KT2440 for the fermentative production of N-methylglutamate from simple carbon sources and monomethylamine. P. putida KT2440, which is generally recognized as safe and grows with glucose and the alternative feedstock glycerol as sole carbon and energy source, was engineered for the production of N-methylglutamate using heterologous enzymes from Methylobacterium extorquens. About 3.9 g L−1 N-methylglutamate accumulated within 48 h in shake flask cultures with minimal medium containing monomethylamine and glycerol. A fed-batch cultivation process yielded a N-methylglutamate titer of 17.9 g L−1.
Indoor Positioning Based on Bluetooth Low-Energy Beacons Adopting Graph Optimization

Bluetooth Low-Energy (BLE) beacons-based indoor positioning is a promising method for indoor positioning, especially in applications of position-based services (PbS). It has low deployment cost and it is suitable for a wide range of mobile devices. Existing BLE beacon-based positioning methods can be categorized as range-based methods and fingerprinting-based methods. For range-based methods, the positions of the beacons should be known before positioning. For fingerprinting-based methods, a pre-requisite is the reference fingerprinting map (RFM). Many existing methods focus on how to perform the positioning assuming the beacon positions or RFM are known. However, in practical applications, determining the beacon positions or RFM in the indoor environment is normally a difficult task. This paper proposed an efficient and graph optimization-based way for estimating the beacon positions and the RFM, which combines the range-based method and the fingerprinting-based method. The method exists without need for any dedicated surveying instruments. A user equipped with a BLE-enabled mobile device walks in the region collecting inertial readings and BLE received signal strength indication (RSSI) readings. The inertial measurements are processed through the pedestrian dead reckoning (PDR) method to generate the constraints at adjacent poses. In addition, the BLE fingerprints are adopted to generate constraints between poses (with similar fingerprints) and the RSSIs are adopted to generate distance constraints between the poses and the beacon positions (according to a pre-defined path-loss model). The constraints are then adopted to form a cost function with a least square structure. By minimizing the cost function, the optimal user poses at different times and the beacon positions are estimated. In addition, the RFM can be generated through the pose estimations. Experiments are carried out, which validates that the proposed method for estimating the pre-requisites (including beacon positions and the RFM). These estimated pre-requisites are of sufficient quality for both range-based and fingerprinting-based positioning.
Frequency of vital sign measurement among intubated patients in the general ward and nurses’ attitudes toward vital sign measurement

Purpose The lack of recognition of respiratory distress may result in emergency tracheal intubation in the general ward. However, few studies have examined the differences in the frequency of vital sign measurement between patients with and without emergency tracheal intubation in the general ward. Thus, this study aimed to investigate the differences in the frequency of vital sign measurements between patients with and without emergency tracheal intubation. Patients and methods This is a single-center, retrospective, observational study of unplanned intensive care unit (ICU) admissions from the general wards between December 2015 and February 2017. This study included patients with emergency medical intubations in the general ward who were then transferred to the ICU. Vital signs measured within 24 hours prior to ICU admission were compared between patients who did and did not require emergency tracheal intubation in the general ward. A survey was also conducted to explore the nurses’ attitudes toward vital sign measurements. Results Compared with other vital signs, the respiratory rate was significantly less frequently measured. Moreover, the frequency of respiratory rate measurement was lower in the 38 patients who were intubated than in the 102 patients who were not intubated in the general ward (P=0.07). The survey revealed that 54% of the participating nurses considered assessment of the respiratory rate as the most troublesome nursing task and ~15% of nurses did not routinely measure respiratory rates. Conclusion Respiratory rate was less frequently assessed in deteriorating patients in the general ward, possibly because it was considered a troublesome task.
The Validity of Optical Coherence Tomography Angiography as a Screening Test for the Early Detection of Retinal Changes in Patients with Hydroxychloroquine Therapy

ABSTRACT Purpose: The aim of this study was to quantitatively compare both the vessel density of macular capillary plexuses and the foveal avascular zone (FAZ) areas of patients receiving hydroxychloroquine (HCQ) therapy for more than 5 years while using age- and sex-matched controls. Methods: The patients undergoing HCQ who were screened for toxic effects were evaluated. The FAZ parameters included the area, perimeter, and the acircularity index. The foveal density and vessel density values of both the superficial capillary plexus (SCP) and deep capillary plexus (DCP) were measured using optical coherence tomography angiography (OCTA). Results: This study included 80 eyes of 40 subjects: 20 subjects in the HCQ group and 20 subjects in the control group. The FAZ perimeter and the FAZ area in the SCP and full retinal vasculature were significantly larger in the HCQ group than in the control group (p < 0.05 for all). Additionally, the vessel density of fovea in the SCP and DCP was significantly lower in the HCQ group than in the control group (p < 0.05 for all). Conclusions: OCTA provides objective documentation about FAZ and vessel density features in patients using long-term HCQ therapy before toxicity begins, and it can be used as a screening tool for detecting early changes in the macula.
Cortical markers of auditory stream segregation revealed for streaming based on tonotopy but not pitch

The brain decomposes mixtures of sounds, such as competing talkers, into perceptual streams that can be attended to individually. Attention can enhance the cortical representation of streams, but it is unknown what acoustic features the enhancement reflects, or where in the auditory pathways attentional enhancement is first observed. Here, behavioral measures of streaming were combined with simultaneous low- and high-frequency envelope-following responses (EFR) that are thought to originate primarily from cortical and subcortical regions, respectively. Repeating triplets of harmonic complex tones were presented with alternating fundamental frequencies. The tones were filtered to contain either low-numbered spectrally resolved harmonics, or only high-numbered unresolved harmonics. The behavioral results confirmed that segregation can be based on either tonotopic or pitch cues. The EFR results revealed no effects of streaming or attention on subcortical responses. Cortical responses revealed attentional enhancement under conditions of streaming, but only when tonotopic cues were available, not when streaming was based only on pitch cues. The results suggest that the attentional modulation of phase-locked responses is dominated by tonotopically tuned cortical neurons that are insensitive to pitch or periodicity cues.
Seeing All From a Few: $\ell_{1}$ -Norm-Induced Discriminative Prototype Selection

Prototype selection aims to remove redundancy and irrelevance from large-scale data by selecting an informative subset, which makes it possible to see all data from a few prototypes. However, due to the outliers and uncertain distribution of the data, the selected prototypes are generally less representative and diversified. To alleviate this issue, we develop, in this paper, a <inline-formula> <tex-math notation="LaTeX">$\ell _{1}$ </tex-math></inline-formula>-norm-induced discriminative prototype selection model (<inline-formula> <tex-math notation="LaTeX">$\ell _{1}$ </tex-math></inline-formula>-ProSe). Inspired by the good performance of sparse representation, the sparsity property of data is rationally exploited in the formulated model. Meanwhile, to characterize the pairwise similarity in the learned sparse representation space, a more promising <inline-formula> <tex-math notation="LaTeX">$\ell _{1}$ </tex-math></inline-formula>-norm metric is applied for robust selection instead of the popularly used Euclidean metric in previous works. Considering the convexity of the model to be solved, a composite block coordinate descent solver is presented with rigorous theoretical analysis on its convergence. Furthermore, we extend our model to support online prototype selection by using already obtained prototypes and newly arrived data. Experimental results on synthetic data sets and some applications such as video summarization, motion segmentation, and scene categorization demonstrate that the proposed method is considerably superior to the state-of-the-art methods in the prototype selection.
Associations Between Pancreatic Lipids and &bgr;-Cell Function in Black African and White European Men With Type 2 Diabetes

CONTEXT Intrapancreatic lipid (IPL) has been linked to β-cell dysfunction. Black populations disproportionately develop type 2 diabetes (T2D) and show distinctions in β-cell function compared with white populations. OBJECTIVE We quantified IPL in white European (WE) and black West African (BWA) men with early T2D and investigated the relationships between IPL and β-cell insulin secretory function (ISF). DESIGN, SETTING, AND PARTICIPANTS We performed a cross-sectional assessment of 18 WE and 19 BWA middle-age men with early T2D as part of the South London Diabetes and Ethnicity Phenotyping study. MAIN OUTCOME MEASURES The participants underwent Dixon MRI to determine IPL in the pancreatic head, body, and tail and subcutaneous and visceral adipose tissue volumes. Modeled first- and second-phase ISFs were comprehensively determined using C-peptide measurements during a 3-hour meal tolerance test and a 2-hour hyperglycemic clamp test. RESULTS The WE men had greater mean IPL levels compared with BWA men (P = 0.029), mainly owing to greater IPL levels in the pancreatic head (P = 0.009). The mean IPL level was inversely associated with orally stimulated first-phase ISF in WE but not BWA men (WE, r = -0.554, P = 0.026; BWA, r = -0.183, P = 0.468). No association was found with orally stimulated second-phase ISF in either WE or BWA men. No associations were found between the mean IPL level and intravenously stimulated ISF. CONCLUSIONS The IPL levels were lower in BWA than WE men with early T2D, and the lack of inverse association with first-phase ISF in BWA men indicates that IPL might be a less important determinant of the development of T2D in BWA than in WE men.
Shank and Zinc Mediate an AMPA Receptor Subunit Switch in Developing Neurons

During development, pyramidal neurons undergo dynamic regulation of AMPA receptor (AMPAR) subunit composition and density to help drive synaptic plasticity and maturation. These normal developmental changes in AMPARs are particularly vulnerable to risk factors for Autism Spectrum Disorders (ASDs), which include loss or mutations of synaptic proteins and environmental insults, such as dietary zinc deficiency. Here, we show how Shank2 and Shank3 mediate a zinc-dependent regulation of AMPAR function and subunit switch from GluA2-lacking to GluA2-containing AMPARs. Over development, we found a concomitant increase in Shank2 and Shank3 with GluA2 at synapses, implicating these molecules as potential players in AMPAR maturation. Since Shank activation and function require zinc, we next studied whether neuronal activity regulated postsynaptic zinc at glutamatergic synapses. Zinc was found to increase transiently and reversibly with neuronal depolarization at synapses, which could affect Shank and AMPAR localization and activity. Elevated zinc induced multiple functional changes in AMPAR, indicative of a subunit switch. Specifically, zinc lengthened the decay time of AMPAR-mediated synaptic currents and reduced their inward rectification in young hippocampal neurons. Mechanistically, both Shank2 and Shank3 were necessary for the zinc-sensitive enhancement of AMPAR-mediated synaptic transmission and act in concert to promote removal of GluA1 while enhancing recruitment of GluA2 at pre-existing Shank puncta. These findings highlight a cooperative local dynamic regulation of AMPAR subunit switch controlled by zinc signaling through Shank2 and Shank3 to shape the biophysical properties of developing glutamatergic synapses. Given the zinc sensitivity of young neurons and its dependence on Shank2 and Shank3, genetic mutations and/or environmental insults during early development could impair synaptic maturation and circuit formation that underlie ASD etiology.
Blast-Exposed Veterans With Mild Traumatic Brain Injury Show Greater Frontal Cortical Thinning and Poorer Executive Functioning

Objective: Blast exposure (BE) and mild traumatic brain injury (mTBI) have been independently linked to pathological brain changes. However, the combined effects of BE and mTBI on brain structure have yet to be characterized. Therefore, we investigated whether regional differences in cortical thickness exist between mTBI Veterans with and without BE while on deployment. We also examined whether cortical thickness (CT) and cognitive performance differed among mTBI Veterans with low vs. high levels of cumulative BE. Methods: 80 Veterans with mTBI underwent neuroimaging and completed neuropsychological testing and self-report symptom rating scales. Analyses of covariance (ANCOVA) were used to compare blast-exposed Veterans (mTBI+BE, n = 51) to those without BE (mTBI-BE, n = 29) on CT of frontal and temporal a priori regions of interest (ROIs). Next, multiple regression analyses were used to examine whether CT and performance on an executive functions composite differed among mTBI Veterans with low (mTBI+BE Low, n = 22) vs. high (mTBI+BE High, n = 26) levels of cumulative BE. Results: Adjusting for age, numer of TBIs, and PTSD symptoms, the mTBI+BE group showed significant cortical thinning in frontal regions (i.e., left orbitofrontal cortex [p = 0.045], left middle frontal gyrus [p = 0.023], and right inferior frontal gyrus [p = 0.034]) compared to the mTBI-BE group. No significant group differences in CT were observed for temporal regions (p's > 0.05). Multiple regression analyses revealed a significant cumulative BE × CT interaction for the left orbitofrontal cortex (p = 0.001) and left middle frontal gyrus (p = 0.020); reduced CT was associated with worse cognitive performance in the mTBI+BE High group but not the mTBI+BE Low group. Conclusions: Findings show that Veterans with mTBI and BE may be at risk for cortical thinning post-deployment. Moreover, our results demonstrate that reductions in CT are associated with worse executive functioning among Veterans with high levels of cumulative BE. Future longitudinal studies are needed to determine whether BE exacerbates mTBI-related cortical thinning or independently negatively influences gray matter structure.
Managing Local Stressors for Coral Reef Condition and Ecosystem Services Delivery Under Climate Scenarios

Coral reefs provide numerous ecosystem goods and services, but are threatened by multiple environmental and anthropogenic stressors. To identify management scenarios that will reverse or mitigate ecosystem degradation, managers can benefit from tools that can quantify projected changes in ecosystem services due to alternative management options. We used a spatially-explicit biophysical ecosystem model to evaluate socio-ecological trade-offs of land-based vs. marine-based management scenarios, and local-scale vs. global-scale stressors and their cumulative impacts. To increase the relevance of understanding ecological change for the public and decision-makers, we used four ecological production functions to translate the model outputs into the ecosystem services: “State of the Reef,” “Trophic Integrity,” “Fisheries Production,” and “Fisheries Landings. ” For a case study of Maui Nui, Hawai’i, land-based management attenuated coral cover decline whereas fisheries management promoted higher total fish biomass. Placement of no-take marine protected areas (MPAs) across 30% of coral reef areas led to a reversal of the historical decline in predatory fish biomass, although this outcome depended on the spatial arrangement of MPAs. Coral cover declined less severely under strict sediment mitigation scenarios. However, the benefits of these local management scenarios were largely lost when accounting for climate-related impacts. Climate-related stressors indirectly increased herbivore biomass due to the shift from corals to algae and, hence, greater food availability. The two ecosystem services related to fish biomass increased under climate-related stressors but “Trophic Integrity” of the reef declined, indicating a less resilient reef. “State of the Reef” improved most and “Trophic Integrity” declined least under an optimistic global warming scenario and strict local management. This work provides insight into the relative influence of land-based vs. marine-based management and local vs. global stressors as drivers of changes in ecosystem dynamics while quantifying the tradeoffs between conservation- and extraction-oriented ecosystem services.
Liraglutide Promotes the Osteogenic Differentiation in MC3T3-E1 Cells Via Regulating the Expression of Smad2/3 Through PI3K/Akt and Wnt/β-Catenin Pathways.

Diabetes is a worldwide health problem with increasing prevalence. Some reports indicate the interplay between bone and glucose metabolism. The imbalance between bone resorption and formation resulted in the structural integrity and strength of bone. Glucagon-like peptide-1 (GLP-1) and its agonists (Liraglutide) have an anabolic action on bone remodeling by stimulating osteoblast differentiation as well as increasing osteoblast longevity. However, the underlying mechanisms remain elusive. We detected the presence of GLP-1 receptor (GLP-1R) in MC3T3-E1 cells via immunocytochemistry assay. Alkaline phosphatase activity assay, alizarin red stain, quantitative real-time polymerase chain reaction, and western blot were employed to detect the effect of Liraglutide on osteogenic differentiation. Liraglutide promoted the expression of GLP-1R in a dosage- and time-dependent manner, and it enhanced the osteogenic differentiation in MC3T3-E1 cells. Liraglutide application improved the levels of Smad2/3 and p-Smad2/3; however, the silencing of Smad2/3 blocked the osteogenic differentiation induced by Liraglutide. What is more, the application of PI3K and Wnt inhibitors inhibited the upregulation of Akt, p-Akt, β-catenin, Smad2/3, and p-Smad2/3 induced by Liraglutide. Liraglutide facilitated the osteogenic differentiation via the regulation of Smad2/3 via PI3K/AKT and Wnt/β-catenin pathways. These data revealed a new mechanism of Liraglutide inducing osteogenic differentiation and provided theory evidence to maintain normal bone metabolism during diabetes therapy.
Intraductal papillary mucinous neoplasm to pancreas ductal adenocarcinoma sequence and pancreas cancer screening

314 Address for correspondence Dr. James J. Farrell, Department of Digestive Diseases, Yale Center for Pancreatic Diseases, Yale School of Medicine, LMP 1080, 15 York Street, New Haven, Connecticut 06510‐3221, USA. E‐mail: james.j.farrell@yale.edu Received: 2018-06-28; Accepted: 2018-07-27; Published online: 2018-10-15 Intraductal papillary mucinous neoplasm to pancreas ductal adenocarcinoma sequence and pancreas cancer screening