Miracle-dz/UniFAR-FTUs huggingface dataset:
Overcoming catastrophic forgetting in neural networks

Significance Deep neural networks are currently the most successful machine-learning technique for solving a variety of tasks, including language translation, image classification, and image generation. One weakness of such models is that, unlike humans, they are unable to learn multiple tasks sequentially. In this work we propose a practical solution to train such models sequentially by protecting the weights important for previous tasks. This approach, inspired by synaptic consolidation in neuroscience, enables state of the art results on multiple reinforcement learning problems experienced sequentially. The ability to learn tasks in a sequential fashion is crucial to the development of artificial intelligence. Until now neural networks have not been capable of this and it has been widely thought that catastrophic forgetting is an inevitable feature of connectionist models. We show that it is possible to overcome this limitation and train networks that can maintain expertise on tasks that they have not experienced for a long time. Our approach remembers old tasks by selectively slowing down learning on the weights important for those tasks. We demonstrate our approach is scalable and effective by solving a set of classification tasks based on a hand-written digit dataset and by learning several Atari 2600 games sequentially.
Data Validation and Sensor Life Prediction Layer on Cloud for IoT

The Internet of Things (IoT) opens up unlimited possibilities. The core of IoT lies in its ability to collect data and actuate any "thing" ranging from monitoring and controlling complicated machines, to setting up mood lighting at home or monitoring the vital signs of a bedridden patient. At the heart of each of these possibilities—of all IoT possibility—is a wide range of sensors connected to a cloud infrastructure that can collate sensor data. The shelf-life and reliability of these sensors will vary widely, primarily because of the diversity of the environments and conditions in which they sensors operate. While it's possible to build data validation logic close to the sensor, it's not always practical given restrictions around power requirements, compute availability, and cost. The paper discusses pragmatic approaches to validating and correcting sensor data, and leveraging faulty sensor data to train cloud-based models that would predict sensor life. In addition, the paper discusses the possibilities of validating the correctness of the prediction models.
ALPPS Improves Resectability Compared With Conventional Two-stage Hepatectomy in Patients With Advanced Colorectal Liver Metastasis

Objective: The aim of the study was to evaluate if associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) could increase resection rates (RRs) compared with two-stage hepatectomy (TSH) in a randomized controlled trial (RCT). Background: Radical liver metastasis resection offers the only chance of a cure for patients with metastatic colorectal cancer. Patients with colorectal liver metastasis (CRLM) and an insufficient future liver remnant (FLR) volume are traditionally treated with chemotherapy with portal vein embolization or ligation followed by hepatectomy (TSH). This treatment sometimes fails due to insufficient liver growth or tumor progression. Methods: A prospective, multicenter RCT was conducted between June 2014 and August 2016. It included 97 patients with CRLM and a standardized FLR (sFLR) of less than 30%. Primary outcome—RRs were measured as the percentages of patients completing both stages of the treatment. Secondary outcomes were complications, radicality, and 90-day mortality measured from the final intervention. Results: Baseline characteristics, besides body mass index, did not differ between the groups. The RR was 92% [95% confidence interval (CI) 84%–100%] (44/48) in the ALPPS arm compared with 57% (95% CI 43%–72%) (28/49) in the TSH arm [rate ratio 8.25 (95% CI 2.6–26.6); P < 0.0001]. No differences in complications (Clavien–Dindo ≥3a) [43% (19/44) vs 43% (12/28)] [1.01 (95% CI 0.4–2.6); P = 0.99], 90-day mortality [8.3% (4/48) vs 6.1% (3/49)] [1.39 [95% CI 0.3–6.6]; P = 0.68] or R0 RRs [77% (34/44) vs 57% (16/28)] [2.55 [95% CI 0.9–7.1]; P = 0.11)] were observed. Of the patients in the TSH arm that failed to reach an sFLR of 30%, 12 were successfully treated with ALPPS. Conclusion: ALPPS is superior to TSH in terms of RR, with comparable surgical margins, complications, and short-term mortality.
Retracted: Genistein mediated histone acetylation and demethylation activates tumor suppressor genes in prostate cancer cells

The above article, published online on 22 April 2008 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the authors, the journal Editor in Chief, Prof. Peter Lichter, and John Wiley & Sons Ltd. The retraction has been agreed due to errors identified in Figs, 3, 4, and 5. The concerns about these figures cannot be resolved because the original data can no longer be retrieved.
Effect of HIV-infection and cumulative viral load on age-related decline in grip strength

Objective:Grip strength predicts functional decline and death, and is regarded as a biomarker of biological aging. The primary objective of this manuscript was to assess differences in the rate of decline in grip strength in persons aging with and without HIV. Design:Grip strength was assessed in 1552 (716 HIV+ and 836 HIV−) men aged at least 50 years participating in the Multicenter AIDS Cohort Study between 2007 and 2014. Methods:Grip strength decline was modeled longitudinally, adjusting for serostatus, demographics, comorbidities, and conditions. In HIV-specific models, coefficients were included for cumulative viral load and history of AIDS. Results:Grip strength at the age of 50 years averaged 37.9 and 38.2 kg for HIV+ and HIV− men, respectively (P = 0.70). In fully adjusted models, grip strength declined 0.33 kg/year in HIV− men (P < 0.001) and 0.42 kg/year in HIV+ men (P = 0.01). In HIV-stratified models, higher cumulative viral load indicated greater strength decline (−0.884 kg for 3.1–4.0 log10 copies-years/ml and −1.077 kg for ≥4.1 log10 copies-years/ml) relative to men with consistently low viral load (⩽3.0 log10 copies-years/ml). Adjusted Cox proportional hazard models revealed a 70% greater risk of clinically weak grip strength in HIV+ men (adjusted hazard ratio 1.70; 95% confidence interval, 1.22–2.40). Conclusion:Grip strength decline is accelerated in HIV-infected men, which may contribute to decreased life expectancy and lower quality of life with aging. Greater cumulative viral load exposure appears to be an important driver of this decline and underscores the importance of early initiation of therapy.
InLoc: Indoor Visual Localization with Dense Matching and View Synthesis

We seek to predict the 6 degree-of-freedom (6DoF) pose of a query photograph with respect to a large indoor 3D map. The contributions of this work are three-fold. First, we develop a new large-scale visual localization method targeted for indoor spaces. The method proceeds along three steps: (i) efficient retrieval of candidate poses that scales to large-scale environments, (ii) pose estimation using dense matching rather than sparse local features to deal with weakly textured indoor scenes, and (iii) pose verification by virtual view synthesis that is robust to significant changes in viewpoint, scene layout, and occlusion. Second, we release a new dataset with reference 6DoF poses for large-scale indoor localization. Query photographs are captured by mobile phones at a different time than the reference 3D map, thus presenting a realistic indoor localization scenario. Third, we demonstrate that our method significantly outperforms current state-of-the-art indoor localization approaches on this new challenging data. Code and data are publicly available.
Identification of the amino acids inserted during suppression of CFTR nonsense mutations and determination of their functional consequences

In-frame premature termination codons (PTCs) account for ∼11% of all disease-associated mutations. PTC suppression therapy utilizes small molecules that suppress translation termination at a PTC to restore synthesis of a full-length protein. PTC suppression is mediated by the base pairing of a near-cognate aminoacyl-tRNA with a PTC and subsequently, the amino acid becomes incorporated into the nascent polypeptide at the site of the PTC. However, little is known about the identity of the amino acid(s) inserted at a PTC during this process in mammalian cells, or how the surrounding sequence context influences amino acid incorporation. Here, we determined the amino acids inserted at the cystic fibrosis transmembrane conductance regulator (CFTR) W1282X PTC (a UGA codon) in the context of its three upstream and downstream CFTR codons during G418-mediated suppression. We found that leucine, cysteine and tryptophan are inserted during W1282X suppression. Interestingly, these amino acids (and their proportions) are significantly different from those recently identified following G418-mediated suppression of the CFTR G542X UGA mutation. These results demonstrate for the first time that local mRNA sequence context plays a key role in near-cognate aminoacyl-tRNA selection during PTC suppression. We also found that some variant CFTR proteins generated by PTC suppression exhibit reduced maturation and activity, indicating the complexity of nonsense suppression therapy. However, both a CFTR corrector and potentiator enhanced activity of protein variants generated by G418-mediated suppression. These results suggest that PTC suppression in combination with CFTR modulators may be beneficial for the treatment of CF patients with PTCs.
Influence Maximization in a Many Cascades World

Online Social Networks (OSNs) are widely utilized in viral marketing campaigns exploiting the word-of-mouth effect. Various propagation models have been proposed to describe the way cascades unfold in OSNs. Based on the existing propagation models, several studies address the problem of influence maximization, where the objective is to identify an appropriate subset of users to initiate the spread of a contagion. However, existing approaches ignore an important factor in the propagation process, i.e., the correlation of multiple contagions simultaneously cascading in the social network and how these affect the users' decisions regarding the adoption of a contagion. Although recent works look into either the competition or the complementarity among a pair of contagions, a uniform model that describes the propagation of multiple cascades with varying types and degrees of correlations is lacking. This work constitutes the first attempt to fill this gap. We formulate a novel propagation model, the Correlated Contagions Dynamic Linear Threshold (CCDLT), that considers the correlation of many contagions in either competitive or complementary manner. Our proposed model allows for different degrees of competition/complementarity among cascades. We further consider that users may dynamically switch states regarding the contagion they promote during the propagation process, based on the influence of their neighborhoods. We then design a greedy seed selection algorithm that identifies the appropriate subset of users to participate in a specific contagion in order to maximize its spread and we formally prove that it approximates the best solution at a ratio of 1 - 1/e. Through an extensive experimental evaluation we demonstrate the superiority of our approach over existing schemes.
Is preterm placental calcification related to adverse maternal and foetal outcome?

Abstract This prospective cohort study aimed to evaluate the role of premature placental calcification in adverse pregnancy outcomes and identify its associated potential risk factors. We consecutively enrolled 293 women who presented to three academic medical centres from September 2011 to March 2013. Participants underwent transabdominal sonographies between 28–36 weeks of gestation in an attempt to determine placental maturity. We compared maternal and foetal outcomes between two groups of women, those with grade III placenta (n = 69) and those without grade III placenta (n = 224). Passive smoking was the only predictor of early placental calcification. There were more abnormal Doppler, low birth weight (LBW) and caesarean section (CS) deliveries observed in the preterm calcification group. No definite relationship existed between maternal hypertension (HTN), diabetes and other medical diseases with placental calcification. In conclusion, umbilical artery (UA) resistance index (RI) and absent or reversed end-diastolic velocity (AREDV) were observed more often in preterm placental calcification. Serious antepartum follow-up should be advised for these mothers. Impact Statement • Placental calcification is a physiological phenomenon but normally, a grade III placenta is not frequently found until 36 weeks of gestation (so is called preterm placental calcification – PPC). There is currently a lack of consistent evidence on the clinical significance of PPC and pregnancy outcome. The present study was designed to evaluate the role of PPC in adverse pregnancy outcomes. • In our study, although none of the pregnant women were smokers, we found that passive smoking was the only predictor of PPC. Abnormal umbilical artery Doppler waveforms considerably and absent end diastolic velocity pattern significantly were observed more often in the PPC group. • We observed that PPC can be a landmark for high-risk pregnancy and an alarm sign for placental dysfunction. So, close antepartum follow up should be advised for these mothers. Regular and frequent foetal wellbeing tests should be done to prevent pregnancy complications. Certainly larger and more extensive study can provide more valid results.
Specific deletion of LKB1/Stk11 in the Müllerian duct mesenchyme drives hyperplasia of the periurethral stroma and tumorigenesis in male mice

Significance Symptoms of benign prostatic hyperplasia (BPH) affect many older men, but the etiology of the disease is largely unknown. We show that male mice develop prostatic stromal hyperplasia accompanied by lower urinary tract symptoms that appear similar to BPH with conditional homozygous deletion of the tumor suppressor gene, Stk11 (serine threonine kinase 11), in the Müllerian duct mesenchyme (MDM), which regresses in males during early fetal development. Cell lineage tracing studies confirmed that cells from the caudal MDM contribute to the stromal cell population of the dorsal periurethral area, which has been compared with the transition zone of the human prostate. These studies show that some of the stromal cells of the prostate are MD-derived, and that their mutation can lead to BPH. Nearly all older men will experience lower urinary tract symptoms associated with benign prostatic hyperplasia (BPH), the etiology of which is not well understood. We have generated Stk11CKO mice by conditional deletion of the liver kinase B1 (LKB1) tumor suppressor gene, Stk11 (serine threonine kinase 11), in the fetal Müllerian duct mesenchyme (MDM), the caudal remnant of which is thought to be assimilated by the urogenital sinus primordial mesenchyme in males during fetal development. We show that MDM cells contribute to the postnatal stromal cells at the dorsal aspect of the prostatic urethra by lineage tracing. The Stk11CKO mice develop prostatic hyperplasia with bladder outlet obstruction, most likely because of stromal expansion. The stromal areas from prostates of Stk11CKO mice, with or without significant expansion, were estrogen receptor positive, which is consistent with both MD mesenchyme-derived cells and the purported importance of estrogen receptors in BPH development and/or progression. In some cases, stromal hyperplasia was admixed with epithelial metaplasia, sometimes with keratin pearls, consistent with squamous cell carcinomas. Mice with conditional deletion of both Stk11 and Pten developed similar features as the Stk11CKO mice, but at a highly accelerated rate, often within the first few months after birth. Western blot analyses showed that the loss of LKB1 and phosphatase and tensin homolog deleted on chromosome 10 (PTEN) induces activation of the phospho-5′ adenosine monophosphate-activated protein kinase and phospho-AKT serine/threonine kinase 1 signaling pathways, as well as increased total and active β-catenin. These results suggest that activation of these signaling pathways can induce hyperplasia of the MD stroma, which could play a significant role in the etiology of human BPH.
Cancer mortality in Yukon 1999–2013: elevated mortality rates and a unique cancer profile

ABSTRACT Background: Although cancer is the leading cause of death in Canada, cancer in the North has been incompletely described. Objective: To determine cancer mortality rates in the Yukon Territory, compare them with Canadian rates, and identify major causes of cancer mortality. Design: The Yukon Vital Statistics Registry provided all cancer deaths for Yukon residents between 1999-2013. Age-standardised mortality rates (ASMRs) were calculated using direct standardisation and compared with Canadian rates. Standardised mortality ratios (SMRs) were calculated using indirect standardisation relative to age-specific rates from Canada, British Columbia (BC), and three sub-provincial BC administrative health regions : Interior Health (IH), Northern Health (NH) and Vancouver Coastal Health (VCH). Trends in smoothed ASMRs were examined with graphical methods. Results: Yukon’s all-cancer ASMRs were elevated compared with national and provincial rates for the entire period. Disparities were greatest compared with the urban VCH: prostate (SMRVCH=246.3, 95% CI 140.9–351.6), female lung (SMRVCH=221.2, 95% CI 154.3–288.1), female breast (SMRVCH=169.0 95% CI, 101.4–236.7), and total colorectal (SMRVCH=149.3, 95% CI 101.8–196.8) cancers were significantly elevated. Total stomach cancer mortality was significantly elevated compared with all comparators. Conclusions: Yukon cancer mortality rates were elevated compared with national, provincial, urban, and southern-rural jurisdictions. More research is required to elucidate these differences.
On Derandomizing Local Distributed Algorithms

The gap between the known randomized and deterministic local distributed algorithms underlies arguably the most fundamental and central open question in distributed graph algorithms. In this paper, we combine the method of conditional expectation with network decompositions to obtain a generic and clean recipe for derandomizing LOCAL algorithms. This leads to significant improvements on a number of problems, in cases resolving known open problems. Two main results are: - An improved deterministic distributed algorithm for hypergraph maximal matching, improving on Fischer, Ghaffari, and Kuhn [FOCS '17]. This yields improved algorithms for edge-coloring, maximum matching approximation, and low out-degree edge orientation. The last result gives the first positive resolution in the Open Problem 11.10 in the book of Barenboim and Elkin. - Improved randomized and deterministic distributed algorithms for the Lovász Local Lemma, which get closer to a conjecture of Chang and Pettie [FOCS '17].
Phytosphingosine degradation pathway includes fatty acid α-oxidation reactions in the endoplasmic reticulum

Significance Although the synthetic pathway of phytosphingosine is already known, its degradation pathway has remained unclear. In the present study, we reveal the entire phytosphingosine degradation pathway, where fatty acid α-oxidation is involved. We show that the Sjögren–Larsson syndrome-causative gene ALDH3A2 and HACL2 (2-hydroxyacyl-CoA lyase 2) are involved in the fatty acid α-oxidation reactions as an aldehyde dehydrogenase and a 2-hydroxy acyl-CoA lyase, respectively. Our findings are important for understanding the molecular mechanism of phytosphingosine/sphingolipid homeostasis. HACL2 is localized in the endoplasmic reticulum, indicating that fatty acid α-oxidation occurs in the endoplasmic reticulum in mammals, in addition to the α-oxidation already known to occur in peroxisomes. Although normal fatty acids (FAs) are degraded via β-oxidation, unusual FAs such as 2-hydroxy (2-OH) FAs and 3-methyl-branched FAs are degraded via α-oxidation. Phytosphingosine (PHS) is one of the long-chain bases (the sphingolipid components) and exists in specific tissues, including the epidermis and small intestine in mammals. In the degradation pathway, PHS is converted to 2-OH palmitic acid and then to pentadecanoic acid (C15:0-COOH) via FA α-oxidation. However, the detailed reactions and genes involved in the α-oxidation reactions of the PHS degradation pathway have yet to be determined. In the present study, we reveal the entire PHS degradation pathway: PHS is converted to C15:0-COOH via six reactions [phosphorylation, cleavage, oxidation, CoA addition, cleavage (C1 removal), and oxidation], in which the last three reactions correspond to the α-oxidation. The aldehyde dehydrogenase ALDH3A2 catalyzes both the first and second oxidation reactions (fatty aldehydes to FAs). In Aldh3a2-deficient cells, the unmetabolized fatty aldehydes are reduced to fatty alcohols and are incorporated into ether-linked glycerolipids. We also identify HACL2 (2-hydroxyacyl-CoA lyase 2) [previous name, ILVBL; ilvB (bacterial acetolactate synthase)-like] as the major 2-OH acyl-CoA lyase involved in the cleavage (C1 removal) reaction in the FA α-oxidation of the PHS degradation pathway. HACL2 is localized in the endoplasmic reticulum. Thus, in addition to the already-known FA α-oxidation in the peroxisomes, we have revealed the existence of FA α-oxidation in the endoplasmic reticulum in mammals.
Volatile secondary metabolites as aposematic olfactory signals and defensive weapons in aquatic environments

Significance This report gives empirical evidence indicating that chemoreception of volatile/odorant lipophilic compounds, almost insoluble in water, can occur in aquatic environments, by means of “tactile” forms of olfaction. This thesis has been proved by exploring the defensive role of terpenes isolated from benthic invertebrates. The isolated metabolites were found to act both as defensive toxic weapons and as olfactory signals. In addition, the most abundant compound induced avoidance learning in crustaceans and fish that experienced postingestive negative effects. Olfaction is considered a distance sense; hence, aquatic olfaction is thought to be mediated only by molecules dissolved in water. Here, we challenge this view by showing that shrimp and fish can recognize the presence of hydrophobic olfactory cues by a “tactile” form of chemoreception. We found that odiferous furanosesquiterpenes protect both the Mediterranean octocoral Maasella edwardsi and its specialist predator, the nudibranch gastropod Tritonia striata, from potential predators. Food treated with the terpenes elicited avoidance responses in the cooccurring shrimp Palaemon elegans. Rejection was also induced in the shrimp by the memory recall of postingestive aversive effects (vomiting), evoked by repeatedly touching the food with chemosensory mouthparts. Consistent with their emetic properties once ingested, the compounds were highly toxic to brine shrimp. Further experiments on the zebrafish showed that this vertebrate aquatic model also avoids food treated with one of the terpenes, after having experienced gastrointestinal malaise. The fish refused the food after repeatedly touching it with their mouths. The compounds studied thus act simultaneously as (i) toxins, (ii) avoidance-learning inducers, and (iii) aposematic odorant cues. Although they produce a characteristic smell when exposed to air, the compounds are detected by direct contact with the emitter in aquatic environments and are perceived at high doses that are not compatible with their transport in water. The mouthparts of both the shrimp and the fish have thus been shown to act as “aquatic noses,” supporting a substantial revision of the current definition of the chemical senses based upon spatial criteria.