Miracle-dz/UniFAR-FTUs huggingface dataset:
Consistency of cruise data of the CARINA database in the Atlantic sector of the Southern Ocean

Abstract. Initially a North Atlantic project, the CARINA carbon synthesis was extended to include the Southern Ocean. Carbon and relevant hydrographic and geochemical ancillary data from cruises all across the Arctic Mediterranean Seas, Atlantic and Southern Ocean were released to the public and merged into a new database as part of the CARINA synthesis effort. Of a total of 188 cruises, 37 cruises are part of the Southern Ocean, including 11 from the Atlantic sector. The variables from all Southern Ocean cruises, including dissolved inorganic carbon (TCO2), total alkalinity, oxygen, nitrate, phosphate and silicate, were examined for cruise-to-cruise consistency in one collective effort. Seawater pH and chlorofluorocarbons (CFCs) are also part of the database, but the pH quality control (QC) is described in another Earth System Science Data publication, while the complexity of the Southern Ocean physics and biogeochemistry prevented a proper QC analysis of the CFCs. The area-specific procedures of quality control, including crossover analysis between stations and inversion analysis of all crossover data (i.e. secondary QC), are briefly described here for the Atlantic sector of the Southern Ocean. Data from an existing, quality controlled database (GLODAP) were used as a reference for our computations – however, the reference data were included into the analysis without applying the recommended GLODAP adjustments so the corrections could be independently verified. The outcome of this effort is an internally consistent, high-quality carbon data set for all cruises, including the reference cruises. The suggested corrections by the inversion analysis were allowed to vary within a fixed envelope, thus accounting for natural variability. The percentage of cruises adjusted ranged from 31% (for nitrate) to 54% (for phosphate) depending on the variable.
POSTER: Vulnerability Discovery with Function Representation Learning from Unlabeled Projects

In cybersecurity, vulnerability discovery in source code is a fundamental problem. To automate vulnerability discovery, Machine learning (ML) based techniques has attracted tremendous attention. However, existing ML-based techniques focus on the component or file level detection, and thus considerable human effort is still required to pinpoint the vulnerable code fragments. Using source code files also limit the generalisability of the ML models across projects. To address such challenges, this paper targets at the function-level vulnerability discovery in the cross-project scenario. A function representation learning method is proposed to obtain the high-level and generalizable function representations from the abstract syntax tree (AST). First, the serialized ASTs are used to learn project independence features. Then, a customized bi-directional LSTM neural network is devised to learn the sequential AST representations from the large number of raw features. The new function-level representation demonstrated promising performance gain, using a unique dataset where we manually labeled 6000+ functions from three open-source projects. The results confirm that the huge potential of the new AST-based function representation learning.
Pathological Response in a Triple-Negative Breast Cancer Cohort Treated with Neoadjuvant Carboplatin and Docetaxel According to Lehmann's Refined Classification

Purpose: Triple-negative breast cancer (TNBC) requires the iden- tification of reliable predictors of response to neoadjuvant chemotherapy (NACT). For this purpose, we aimed to evaluate the performance of the TNBCtype-4 classifier in a cohort of patients with TNBC treated with neoadjuvant carboplatin and docetaxel (TCb). Methods: Patients with TNBC were accrued in a nonrandomized trial of neoadjuvant carboplatin AUC 6 and docetaxel 75 mg/m2 for six cycles. Response was evaluated in terms of pathologic complete response (pCR, ypT0/is ypN0) and residual cancer burden by Symmans and colleagues. Lehmann's subtyping was performed using the TNBCtype online tool from RNAseq data, and germline sequencing of a panel of seven DNA damage repair genes was conducted. Results: Ninety-four out of the 121 patients enrolled in the trial had RNAseq available. The overall pCR rate was 44.7%. Lehmann subtype distribution was 34.0% BL1, 20.2% BL2, 23.4% M, 14.9% LAR, and 7.4% were classified as ER+. Response to NACT with TCb was significantly associated with Lehmann subtype (P = 0.027), even in multivariate analysis including tumor size and nodal involvement, with BL1 patients achieving the highest pCR rate (65.6%), followed by BL2 (47.4%), M (36.4%), and LAR (21.4%). BL1 was associated with a significant younger age at diagnosis and higher ki67 values. Among our 10 germline mutation carriers, 30% were BL1, 40% were BL2, and 30% were M. Conclusions: TNBCtype-4 is associated with significantly different pCR rates for the different subtypes, with BL1 and LAR displaying the best and worse responses to NACT, respectively. Clin Cancer Res; 24(8); 1845–52. ©2018 AACR.
Toward Leveraging Human Connectomic Data in Large Consortia: Generalizability of fMRI‐Based Brain Graphs Across Sites, Sessions, and Paradigms

&NA; While graph theoretical modeling has dramatically advanced our understanding of complex brain systems, the feasibility of aggregating connectomic data in large imaging consortia remains unclear. Here, using a battery of cognitive, emotional and resting fMRI paradigms, we investigated the generalizability of functional connectomic measures across sites and sessions. Our results revealed overall fair to excellent reliability for a majority of measures during both rest and tasks, in particular for those quantifying connectivity strength, network segregation and network integration. Processing schemes such as node definition and global signal regression (GSR) significantly affected resulting reliability, with higher reliability detected for the Power atlas (vs. AAL atlas) and data without GSR. While network diagnostics for default‐mode and sensori‐motor systems were consistently reliable independently of paradigm, those for higher‐order cognitive systems were reliable predominantly when challenged by task. In addition, based on our present sample and after accounting for observed reliability, satisfactory statistical power can be achieved in multisite research with sample size of approximately 250 when the effect size is moderate or larger. Our findings provide empirical evidence for the generalizability of brain functional graphs in large consortia, and encourage the aggregation of connectomic measures using multisite and multisession data.
A single dose of epidermicin NI01 is sufficient to eradicate MRSA from the nares of cotton rats

Objectives: To investigate the efficacy of a potent novel antimicrobial protein of mass 6 kDa, epidermicin NI01, for eradicating the nasal burden of MRSA in a cotton rat (Sigmodon hispidus) model. Methods: MRSA strain ATCC 43300 was used to establish a robust colonization of cotton rat nares. This model was used to evaluate the efficacy of topical 0.04% and 0.2% epidermicin NI01, administered twice daily for 3 days consecutively, and topical 0.8% epidermicin NI01 administered once, for reducing nasal MRSA burden. Control groups remained untreated or were administered vehicle only (0.5% hydroxypropylmethylcellulose) or 2% mupirocin twice daily for 3 days. The experiment was terminated at day 5 and MRSA quantitative counts were determined. Tissues recovered from animals treated with 0.2% epidermicin twice daily for 3 days were examined for histological changes. Results: Mupirocin treatment resulted in a reduction in burden of log10 (log R) of 2.59 cfu/nares compared with vehicle (P < 0.0001). Epidermicin NI01 administered once at 0.8% showed excellent efficacy, resulting in a log R of 2.10 cfu/nares (P = 0.0004), which was equivalent to mupirocin. Epidermicin NI01 administered at 0.2% or 0.04% twice daily for 3 days did not have a significant impact on the tissue burden recovered from the nares. Mild to marked histological abnormalities were noted, but these were determined to be reversible. Conclusion: A single dose of topical epidermicin NI01 was as effective as mupirocin administered twice daily for 3 days in eradication of MRSA from the nares of cotton rats. This justifies further development of epidermicin for this indication.
ULTRAFAST DYNAMICS IN FIELD-ENHANCED SATURABLE ABSORBERS

Absorption recovery dynamics of GaAs/AlGaAs field‐enhanced waveguide saturable absorbers are studied by pump‐probe differential transmission measurements. We compare the response of bulk and single quantum well absorbers at different reverse bias levels and pump powers, and find an ultrafast transient in the response, followed by a slower rise before the final recovery. The absorption fully recovers after a few picoseconds, which is an important result for mode‐locked lasers.
Experimental Analysis of Mimivirus Translation Initiation Factor 4a Reveals Its Importance in Viral Protein Translation during Infection of Acanthamoeba polyphaga

ABSTRACT The Acanthamoeba polyphaga mimivirus is the first giant virus ever described, with a 1.2-Mb genome which encodes 979 proteins, including central components of the translation apparatus. One of these proteins, R458, was predicted to initiate translation, although its specific role remains unknown. We silenced the R458 gene using small interfering RNA (siRNA) and compared levels of viral fitness and protein expression in silenced versus wild-type mimivirus. Silencing decreased the growth rate, but viral particle production at the end of the viral cycle was unaffected. A comparative proteomic approach using two-dimensional difference-in-gel electrophoresis (2D-DIGE) revealed deregulation of the expression of 32 proteins in silenced mimivirus, which were defined as up- or downregulated. Besides revealing proteins with unknown functions, silencing R458 also revealed deregulation in proteins associated with viral particle structures, transcriptional machinery, oxidative pathways, modification of proteins/lipids, and DNA topology/repair. Most of these proteins belong to genes transcribed at the end of the viral cycle. Overall, our data suggest that the R458 protein regulates the expression of mimivirus proteins and, thus, that mimivirus translational proteins may not be strictly redundant in relation to those from the amoeba host. As is the case for eukaryotic initiation factor 4a (eIF4a), the R458 protein is the prototypical member of the ATP-dependent DEAD box RNA helicase mechanism. We suggest that the R458 protein is required to unwind the secondary structures at the 5′ ends of mRNAs and to bind the mRNA to the ribosome, making it possible to scan for the start codon. These data are the first experimental evidence of mimivirus translation-related genes, predicted to initiate protein biosynthesis. IMPORTANCE The presence in the genome of a mimivirus of genes coding for many translational processes, with the exception of ribosome constituents, has been the subject of debate since its discovery in 2003. In this work, we focused on the R458 mimivirus gene, predicted to initiate protein biosynthesis. After silencing was performed, we observed that it has no major effect on mimivirus multiplication but that it affects protein expression and fitness. This suggests that it is effectively used by mimivirus during its developmental cycle. Until large-scale genetic manipulation of giant viruses becomes possible, the silencing strategy used here on mimivirus translation-related factors will open the way to understanding the functions of these translational genes.
An Axiomatic Approach to Linear Explanations in Data Classification

In this work, we focus on local explanations for data analytics; in other words: given a datapoint (cid:126) x , how important was the i -th feature in determining the outcome for (cid:126) x ? The literature has seen a recent emergence of various analytical answers to this question. We argue for a linear inﬂuence measure explanation: given a datapoint (cid:126) x , assign a value φ i ( (cid:126) x ) to every feature i , which roughly corresponds to feature i ’s importance in determining the outcome for (cid:126) x . We present a family of measures called MIM (monotone inﬂuence measures), that are uniquely derived from a set of axioms: desirable properties that any reasonable inﬂuence measure should satisfy. Departing from prior work on inﬂuence measures, we assume no knowledge — or access — to the underlying classiﬁer labeling the dataset. In other words, our inﬂuence measures are based on the dataset alone and do not make any queries to the classi-ﬁer. We compare MIM to other linear explanation models in the literature and discuss their underlying assumptions, merits, and limitations.
Low Frequency Variants in the Exons Only Encoding Isoform A of HNF1A Do Not Contribute to Susceptibility to Type 2 Diabetes

Background There is considerable interest in the hypothesis that low frequency, intermediate penetrance variants contribute to the proportion of Type 2 Diabetes (T2D) susceptibility not attributable to the common variants uncovered through genome-wide association approaches. Genes previously implicated in monogenic and multifactorial forms of diabetes are obvious candidates in this respect. In this study, we focussed on exons 8–10 of the HNF1A gene since rare, penetrant mutations in these exons (which are only transcribed in selected HNF1A isoforms) are associated with a later age of diagnosis of Maturity onset diabetes of the young (MODY) than mutations in exons 1–7. The age of diagnosis in the subgroup of HNF1A-MODY individuals with exon 8–10 mutations overlaps with that of early multifactorial T2D, and we set out to test the hypothesis that these exons might also harbour low-frequency coding variants of intermediate penetrance that contribute to risk of multifactorial T2D. Methodology and Principal Findings We performed targeted capillary resequencing of HNF1A exons 8–10 in 591 European T2D subjects enriched for genetic aetiology on the basis of an early age of diagnosis (≤45 years) and/or family history of T2D (≥1 affected sibling). PCR products were sequenced and compared to the published HNF1A sequence. We identified several variants (rs735396 [IVS9−24T>C], rs1169304 [IVS8+29T>C], c.1768+44C>T [IVS9+44C>T] and rs61953349 [c.1545G>A, p.T515T] but no novel non-synonymous coding variants were detected. Conclusions and Significance We conclude that low frequency, nonsynonymous coding variants in the terminal exons of HNF1A are unlikely to contribute to T2D-susceptibility in European samples. Nevertheless, the rationale for seeking low-frequency causal variants in genes known to contain rare, penetrant mutations remains strong and should motivate efforts to screen other genes in a similar fashion.
Research on hot deformation behavior of 3003 Al alloy

3003 Al alloys with different metallurgical quality were obtained by different melt-treatment methods,which were deformed by isothermal compression in the range of deformation temperature 300℃~500℃ at strain rate 0.01s-1~10.0s-1 with Gleeble-1500 thermal simulator.The results show that the material is sensitive to positive strain rate,the linear relationship between the hot deformation activation energy Q and inclusion content H is Q=35.62H+171.58,and the activation energy of 3003 Al alloy prepared by high melt-treatment is the lowest 174.62kJ·mol-1 which is beneficial to the hot plastic deformation of material.The critical strain of 3003 Al alloy prepared by different melt-treatment methods were calculated with work hardening rate,and the critical conditions to predict the dynamic recrystallization occurrence for the 3003 Al alloys prepared by different melt-treatment methods were obtained.
Drug-drug interaction discovery and demystification using Semantic Web technologies

Objective To develop a novel pharmacovigilance inferential framework to infer mechanistic explanations for asserted drug-drug interactions (DDIs) and deduce potential DDIs. Materials and Methods A mechanism-based DDI knowledge base was constructed by integrating knowledge from several existing sources at the pharmacokinetic, pharmacodynamic, pharmacogenetic, and multipathway interaction levels. A query-based framework was then created to utilize this integrated knowledge base in conjunction with 9 inference rules to infer mechanistic explanations for asserted DDIs and deduce potential DDIs. Results The drug-drug interactions discovery and demystification (D3) system achieved an overall 85% recall rate in terms of inferring mechanistic explanations for the DDIs integrated into its knowledge base, while demonstrating a 61% precision rate in terms of the inference or lack of inference of mechanistic explanations for a balanced, randomly selected collection of interacting and noninteracting drug pairs. Discussion The successful demonstration of the D3 system's ability to confirm interactions involving well-studied drugs enhances confidence in its ability to deduce interactions involving less-studied drugs. In its demonstration, the D3 system infers putative explanations for most of its integrated DDIs. Further enhancements to this work in the future might include ranking interaction mechanisms based on likelihood of applicability, determining the likelihood of deduced DDIs, and making the framework publicly available. Conclusion The D3 system provides an early-warning framework for augmenting knowledge of known DDIs and deducing unknown DDIs. It shows promise in suggesting interaction pathways of research and evaluation interest and aiding clinicians in evaluating and adjusting courses of drug therapy.
Reprogramming fibroblasts to pluripotency using arginine-terminated polyamidoamine nanoparticles based non-viral gene delivery system

Induced pluripotent stem cells (iPSCs) have attracted keen interest in regenerative medicine. The generation of iPSCs from somatic cells can be achieved by the delivery of defined transcription factor (Oct4, Sox2, Klf4, and c-Myc[OSKM]). However, most instances of iPSC-generation have been achieved by potentially harmful genome-integrating viral vectors. Here we report the generation of iPSCs from mouse embryonic fibroblasts (MEFs) using arginine-terminated generation 4 polyamidoamine (G4Arg) nanoparticles as a nonviral transfection vector for the delivery of a single plasmid construct carrying OSKM (pOSKM). Our results showed that G4Arg nanoparticles delivered pOSKM into MEFs at a significantly higher transfection efficiency than did conventional transfection reagents. After serial transfections of pOSKM-encapsulated G4Arg nanoparticles, we successfully generated iPSCs from MEFs. Our study demonstrates that G4Arg nanoparticles may be a promising candidate for generating of virus-free iPSCs that have great potential for clinical application.
MicroRNA-21 Knockout Exacerbates Angiotensin II–Induced Thoracic Aortic Aneurysm and Dissection in Mice With Abnormal Transforming Growth Factor-&bgr;–SMAD3 Signaling

Objective— Thoracic aortic aneurysm and dissection (TAAD) are severe vascular conditions. Dysfunctional transforming growth factor-&bgr; (TGF-&bgr;) signaling in vascular smooth muscle cells and elevated angiotensin II (AngII) levels are implicated in the development of TAAD. In this study, we investigated whether these 2 factors lead to TAAD in a mouse model and explored the possibility of using microRNA-21 (miR-21) for the treatment of TAAD. Approach and Results— TAAD was developed in Smad3 (mothers against decapentaplegic homolog 3) heterozygous (S3+/−) mice infused with AngII. We found that p-ERK (phosphorylated extracellular regulated protein kinases)– and p-JNK (phosphorylated c-Jun N-terminal kinase)–associated miR-21 was higher in TAAD lesions. We hypothesize that downregulation of miR-21 mitigate TAAD formation. However, Smad3+/−:miR-21−/− (S3+/−21−/−) mice exhibited conspicuous TAAD formation after AngII infusion. The vascular wall was dilated, and aortic rupture occurred within 23 days during AngII infusion. We then examined canonical and noncanonical TGF-&bgr; signaling and found that miR-21 knockout in S3+/− mice increased SMAD7 and suppressed canonical TGF-&bgr; signaling. Vascular smooth muscle cells lacking TGF-&bgr; signals tended to switch from a contractile to a synthetic phenotype. The silencing of Smad7 with lentivirus prevented AngII-induced TAAD formation in S3+/−21−/− mice. Conclusions— Our study demonstrated that miR-21 knockout exacerbated AngII-induced TAAD formation in mice, which was associated with TGF-&bgr; signaling dysfunction. Therapeutic strategies targeting TAAD should consider unexpected side effects associated with alterations in TGF-&bgr; signaling.
Alveolar Epithelial Type II Cells Activate Alveolar Macrophages and Mitigate P. Aeruginosa Infection

Although alveolar epithelial type II cells (AECII) perform substantial roles in the maintenance of alveolar integrity, the extent of their contributions to immune defense is poorly understood. Here, we demonstrate that AECII activates alveolar macrophages (AM) functions, such as phagocytosis using a conditioned medium from AECII infected by P. aeruginosa. AECII-derived chemokine MCP-1, a monocyte chemoattractant protein, was identified as a main factor in enhancing AM function. We proposed that the enhanced immune potency of AECII may play a critical role in alleviation of bacterial propagation and pneumonia. The ability of phagocytosis and superoxide release by AM was reduced by MCP-1 neutralizing antibodies. Furthermore, MCP-1−/− mice showed an increased bacterial burden under PAO1 and PAK infection vs. wt littermates. AM from MCP-1−/− mice also demonstrated less superoxide and impaired phagocytosis over the controls. In addition, AECII conditioned medium increased the host defense of airway in MCP-1−/− mice through the activation of AM function. Mechanistically, we found that Lyn mediated NFκB activation led to increased gene expression and secretion of MCP-1. Consequently Lyn−/− mice had reduced MCP-1 secretion and resulted in a decrease in superoxide and phagocytosis by AM. Collectively, our data indicate that AECII may serve as an immune booster for fighting bacterial infections, particularly in severe immunocompromised conditions.