bluuebunny/crossref_metadata_2025 huggingface dataset:
Dynamic Stereoselection of Peptide Helicates and Their Selective Labeling of DNA Replication Foci in Cells**
Authors: Gómez‐González Jacobo , Pérez Yolanda , Sciortino Giuseppe , Roldan‐Martín Lorena , Martínez‐Costas José , Maréchal Jean‐Didier , Alfonso Ignacio , Vázquez López Miguel , Vázquez M. Eugenio
Published: December 2020

Although largely overlooked in peptide engineering, coordination chemistry offers a new set of interactions that opens unexplored design opportunities for developing complex molecular structures. In this context, we report new artificial peptide ligands that fold into chiral helicates in the presence of labile metal ions such as FeII and CoII. Heterochiral β‐turn‐promoting sequences encode the stereoselective folding of the peptide ligands and define the physicochemical properties of their corresponding metal complexes. Circular dichroism and NMR spectroscopy in combination with computational methods allowed us to identify and determine the structure of two isochiral ΛΛ‐helicates, folded as topological isomers. Finally, in addition to the in‐vitro characterization of their selective binding to DNA three‐way junctions, cell‐microscopy experiments demonstrated that a rhodamine‐labeled FeII helicate was internalized and selectively stains DNA replication factories in functional cells.
Nanoparticles Supported on Sub‐Nanometer Oxide Films: Scaling Model Systems to Bulk Materials
Authors: Ament Kevin , Köwitsch Nicolas , Hou Dianwei , Götsch Thomas , Kröhnert Jutta , Heard Christopher J. , Trunschke Annette , Lunkenbein Thomas , Armbrüster Marc , Breu Josef
Published: December 2020

Ultrathin layers of oxides deposited on atomically flat metal surfaces have been shown to significantly influence the electronic structure of the underlying metal, which in turn alters the catalytic performance. Upscaling of the specifically designed architectures as required for technical utilization of the effect has yet not been achieved. Here, we apply liquid crystalline phases of fluorohectorite nanosheets to fabricate such architectures in bulk. Synthetic sodium fluorohectorite, a layered silicate, when immersed into water spontaneously and repulsively swells to produce nematic suspensions of individual negatively charged nanosheets separated to more than 60 nm, while retaining parallel orientation. Into these galleries oppositely charged palladium nanoparticles were intercalated whereupon the galleries collapse. Individual and separated Pd nanoparticles were thus captured and sandwiched between nanosheets. As suggested by the model systems, the resulting catalyst performed better in the oxidation of carbon monoxide than the same Pd nanoparticles supported on external surfaces of hectorite or on a conventional Al2O3 support. XPS confirmed a shift of Pd 3d electrons to higher energies upon coverage of Pd nanoparticles with nanosheets to which we attribute the improved catalytic performance. DFT calculations showed increasing positive charge on Pd weakened CO adsorption and this way damped CO poisoning.
Molecular subtyping of hepatocellular carcinoma: A step toward precision medicine
Authors: Wu Yichao , Liu Zhikun , Xu Xiao
Published: December 2020

Hepatocellular carcinoma (HCC) is one of the most prevalent and fatal digestive tumors. Treatment for this disease has been constraint by heterogeneity of this group of tumors, which has greatly limited the progress in personalized therapy. Although existing studies have revealed the genetic and epigenetic blueprints that drive HCCs, many of the molecular mechanisms that lead to HCCs remain elusive. Recent advances in techniques for studying functional genomics, such as genome sequencing and transcriptomic analyses, have led to the discovery of molecular mechanisms that participate in the initiation and evolution of HCC. Integrative multi‐omics analyses have identified several molecular subtypes of HCC associated with specific molecular characteristics and clinical outcomes. Deciphering similar molecular features among highly heterogeneous HCC patients is a prerequisite to implementation of personalized therapeutics. This review summarizes the current research progresses in precision therapy on the backbone of molecular subtypes of HCC.
Systematic Structural Characterization of Chitooligosaccharides Enabled by Automated Glycan Assembly
Authors: Tyrikos‐Ergas Theodore , Bordoni Vittorio , Fittolani Giulio , Chaube Manishkumar A. , Grafmüller Andrea , Seeberger Peter H. , Delbianco Martina
Published: December 2020

Chitin, a polymer composed of β(1–4)‐linked N‐acetyl‐glucosamine monomers, and its partially deacetylated analogue chitosan, are abundant biopolymers with outstanding mechanical as well as elastic properties. Their degradation products, chitooligosaccharides (COS), can trigger the innate immune response in humans and plants. Both material and biological properties are dependent on polymer length, acetylation, as well as the pH. Without well‐defined samples, a complete molecular description of these factors is still missing. Automated glycan assembly (AGA) enabled rapid access to synthetic well‐defined COS. Chitin‐cellulose hybrid oligomers were prepared as important tools for a systematic structural analysis. Intramolecular interactions, identified by molecular dynamics simulations and NMR analysis, underscore the importance of the chitosan amino group for the stabilization of specific geometries.
Phosphorene Supported Single‐Atom Catalysts for CO Oxidation: A Computational Study
Authors: Baskaran Sambath , Xu Cong‐Qiao , Jiang Ya‐Fei , Wang Yang‐Gang , Li Jun
Published: December 2020

Single‐atom catalysts (SACs) have attracted extensive attention owing to their high catalytic activity. The development of efficient SACs is crucial for applications in heterogeneous catalysis. In this article, the geometric configuration, electronic structure, stabilitiy and catalytic performance of phosphorene (Pn) supported single metal atoms (M=Ru, Rh, Pd, Ir, Pt, and Au) have been systematically investigated using density functional theory calculations and ab initio molecular dynamics simulations. The single atoms are found to occupy the hollow site of phosphorene. Among the catalysts studied, Ru‐decorated phosphorene is determined to be a potential catalyst by evaluating adsorption energies of gaseous molecules. Various mechanisms including the Eley‐Rideal (ER), Langmuir‐Hinshelwood (LH) and trimolecular Eley‐Rideal (TER) mechanisms are considered to validate the most favourable reaction pathway. Our results reveal that Ru−Pn exhibits outstanding catalytic activity toward CO oxidation reaction via TER mechanism with the corresponding rate‐determining energy barrier of 0.44 eV, making it a very promising SAC for CO oxidation under mild conditions. Overall, this work may provide a new avenue for the design and fabrication of two‐dimensional materials supported SACs for low‐temperature CO oxidation.
Immobilized Carbohydrates for Preparation of 3′‐Glycoconjugated Oligonucleotides
Authors: Österlund Tommi , Aho Aapo , Äärelä Antti , Tähtinen Ville , Korhonen Heidi , Virta Pasi
Published: December 2020

A detailed protocol for preparation 3′‐glycoconjugated oligonucleotides is described based on one‐pot immobilization of 4,4′‐dimethoxytrityl‐protected carbohydrates to a solid support followed by on‐support peracetylation and automated oligonucleotide assembly. Compared to an appropriate building block approach and post‐synthetic manipulation of oligonucleotides, this protocol may simplify the synthesis scheme and increase overall yield of the conjugates. Furthermore, the immobilization to a solid support typically increases the stability of reactants, enabling prolonged storage, and makes subsequent processing convenient. Automated assembly on these carbohydrate‐modified supports using conventional phosphoramidite chemistry produces 3′‐glycoconjugated oligonucleotides in relatively high yield and purity. © 2020 Wiley Periodicals LLC.

Basic Protocol 1: Synthesis of 1‐O‐tert‐butyldimethylsilyl‐6‐O‐(4,4′‐dimethoxytrityl)‐β‐D‐glucose

Basic Protocol 2: Synthesis of 6‐O‐dimethoxytrityl‐2,3,1′,3′,4′,6′‐hexa‐O‐benzoylsucrose

Basic Protocol 3: Synthesis of 6″‐O‐dimethoxytrityl‐N‐trifluoroacetyl‐protected aminoglycosides

Basic Protocol 4: Synthesis of 3‐O‐dimethoxytrityl‐propyl β‐D‐galactopyranoside

Basic Protocol 5: Synthesis of trivalent N‐acetyl galactosamine cluster

Basic Protocol 6: Synthesis of carbohydrate monosuccinates and their immobilization to a solid support

Basic Protocol 7: Oligonucleotide synthesis using immobilized carbohydrates
The influence of physical activity on the nociceptive flexion reflex in healthy people
Authors: Dhondt Evy , Danneels Lieven , Van Oosterwijck Sophie , Palmans Tanneke , Rijckaert Johan , Van Oosterwijck Jessica
Published: December 2020

Background

The nociceptive flexion reflex (NFR) is a spinal reflex induced by painful stimuli resulting in an appropriate withdrawal response. The NFR is considered to be an objective physiological correlate of spinal nociception. Previous research has already demonstrated that physical activity (PA) can influence pain assessments. To date, no studies have directly examined the relationship between PA and spinal nociception. Hence, this study aimed to investigate whether the NFR threshold can be predicted by report‐based and monitor‐based measures of PA in healthy adults.

Methods

PA and the NFR threshold of 58 healthy adults were assessed. PA was evaluated by self‐report using the International Physical Activity Questionnaire and by monitor‐based accelerometry data. The NFR threshold was elicited through transcutaneous electrical stimulation of the sural nerve and quantified by the biceps femoris muscle electromyogram. Hierarchical linear regression analyses were performed to determine the relationship between PA and the NFR, while controlling for confounders.

Results

Monitor‐based measured step count and activities of moderate‐ to vigorous‐intensity predicted the NFR threshold accounting for 23.0% (p = .047) to 37.1% (p = .002) of the variance. Larger amounts of step counts and higher participation in moderate‐ to vigorous‐intensity activities predicted higher NFR thresholds. Monitor‐based activities of sedentary intensity predicted the NFR threshold accounting for 35.8% (p = .014) to 35.9% (p = .014) of the variance. Spending more time per day on activities of sedentary intensity predicted lower NFR thresholds.

Conclusions

The study provides preliminary evidence indicating that a physically active lifestyle may reduce spinal nociception in healthy adults, while a sedentary lifestyle enhances spinal nociception.

Significance

The present study provides preliminary evidence that the influencing effects of physical activity on pain are the result of a strong descending control and do not purely rely on supraspinal mechanisms. These study results highlight the importance of considering physical activity levels when evaluating nociceptive processing, given the prognostic value of physical activity in spinal nociception. Furthermore, this study encourages future research to examine the effects of moderate‐ to vigorous‐intensity exercise programmes on spinal nociception in chronic pain populations.
Optimization of staggered distance of coal pillars in multiseam mining: Theoretical analysis and numerical simulation
Authors: Sun Xueyang , Lu Mingjiao , Li Cheng
Published: December 2020

Aimed at solving problems related to water retention and loss reduction in multiseam mining, a mechanical model of staggered distance mining was established. First, elastic and plastic slip line field theories were used to calculate the reasonable staggered distance expressions of multiseam mining. The staggered distance schemes of multiseam mining were optimized using the numerical simulation software FLAC3D. By performing an experiment comparing similar materials, the influence on water retention and loss reduction by optimal and unfavorable staggered distance schemes in multiseam mining was explored. The results showed that the σzz curve was distributed in the shape of a “peak” of the staggering distance coal pillars, the Z displacement curve was a “Л,” and the surface subsidence curve was a “W.” Each of these displayed the rule of “decrease then increase.” In staggered distance multiseam mining, the optimal staggered distance value for coal seam Nos. 2 and 3 was 40 m, while the most unfavorable staggered distance value was 0 m. The corresponding subsidence coefficients of the optimal staggered distance values were 0.29, 0.23, and 0.19, under the condition of keeping the optimal staggered distance value for coal seam Nos. 1 and 2 unchanged. These results could be beneficial in reduction of surface subsidence and may also have specific practical engineering significance.
Honey Bees and Neonicotinoid-Treated Corn Seed: Contamination, Exposure, and Effects
Authors: Lin Chia-Hua , Sponsler Douglas B. , Richardson Rodney T. , Watters Harold D. , Glinski Donna A. , Henderson W. Matthew , Minucci Jeffrey M. , Lee E. Henry , Purucker S. Thomas , Johnson Reed M.
Published: December 2020

Most corn (Zea mays) seeds planted in the United States in recent years are coated with a seed treatment containing neonicotinoid insecticides. Abrasion of the seed coating generates insecticide-laden planter dust that disperses through the landscape during corn planting and has resulted in many “bee-kill” incidents in North America and Europe. We investigated the linkage between corn planting and honey bee colony success in a region dominated by corn agriculture. Over 3 yr we consistently observed an increased presence of corn seed treatment insecticides in bee-collected pollen and elevated worker bee mortality during corn planting. Residues of seed treatment neonicotinoids, clothianidin and thiamethoxam, detected in pollen positively correlated with cornfield area surrounding the apiaries. Elevated worker mortality was also observed in experimental colonies fed field-collected pollen containing known concentrations of corn seed treatment insecticides. We monitored colony growth throughout the subsequent year in 2015 and found that colonies exposed to higher insecticide concentrations exhibited slower population growth during the month of corn planting but demonstrated more rapid growth in the month following, though this difference may be related to forage availability. Exposure to seed treatment neonicotinoids during corn planting has clear short-term detrimental effects on honey bee colonies and may affect the viability of beekeeping operations that are dependent on maximizing colony size in the springtime. Environ Toxicol Chem 2021;40:1212–1221. © 2020 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.
Intersecting and 2‐intersecting hypergraphs with maximal covering number: The Erdős–Lovász theme revisited
Authors: Barát János
Published: December 2020

Erdős and Lovász noticed that an ‐uniform intersecting hypergraph with maximal covering number, that is, , must have at least edges. There has been no improvement on this lower bound for 45 years. We try to understand the reason by studying some small cases to see whether the truth lies very close to this simple bound. Let denote the minimum number of edges in an intersecting ‐uniform hypergraph. It was known that and . We obtain the following new results: The extremal example for uniformity 4 is unique. Somewhat surprisingly it is not symmetric by any means. For uniformity 5, , and we found three examples, none of them being some known graph. We use both theoretical arguments and computer searches. In the footsteps of Erdős and Lovász, we also consider the special case, when the hypergraph is part of a finite projective plane. We determine the exact answer for . For uniformity 6, there is a unique extremal example. In a related question, we try to find 2‐intersecting r‐uniform hypergraphs with maximal covering number, that is, . An infinite family of examples is to take all possible r‐sets of a ‐vertex set. There is also a geometric candidate: biplanes. These are symmetric 2‐designs with . We determined that only three biplanes of the 18 known examples are extremal.
Disturbance‐Mediated Apparent Competition Decouples in a Northern Boreal Caribou Range
Authors: Neufeld Branden T. , Superbie Clara , Greuel Ruth J. , Perry Thomas , Tomchuk Patricia A. , Fortin Daniel , McLoughlin Philip D.
Published: December 2020

The most widely reported threat to boreal and mountain populations of woodland caribou (Rangifer tarandus caribou; caribou) involves habitat‐ or disturbance‐mediated apparent competition (DMAC). With DMAC, natural and anthropogenic disturbances that increase the abundance of deciduous‐browsing cervids (e.g., moose [Alces alces], deer [Odocoileus spp.]) are thought to promote predator (especially wolf [Canis lupus]) numbers, which heightens predation risk to caribou. We know most about the effects of DMAC on caribou where the species is under threat by anthropogenic activities in relatively productive southern boreal and mountain systems. Yet, >60% of extant boreal caribou range in North America consists of northern shield and taiga ecoregions of low productivity where caribou may compete with only 1 ungulate species (moose) in the context of DMAC. In this environment, we know very little of how DMAC acts as a limiting factor to caribou. In Saskatchewan, Canada, from 2014–2018, using a combination of vegetation sampling, aerial surveys, and telemetry data (n = 38 wolves), we searched for evidence of DMAC (trends in data consistent with the hypothesis) in an 87,193‐km2 section of the Western Boreal Shield, a poorly productive but pristine region (0.18% of land cover classed as an anthropogenic feature) with a historically high fire‐return interval (47% of stands aged <40 years). Despite the high levels of disturbance, moose density was relatively low (47 moose/1,000 km2), likely because of the scarcity of deciduous or mixed‐wood stands and low abundance of deciduous browse in the young conifer stands that dominated the landscape. In contrast, boreal caribou density was relatively high for the species (37 caribou/1,000 km2). Wolf density (3.1 wolves/1,000 km2) and pack sizes ( = 4.0 wolves/pack) were low and resident (established) territories were large ( = 4,360 km2; 100% minimum convex polygon). The low density of wolves mirrored the low (standardized) ungulate biomass index (UBI; moose + boreal caribou) of the study area (0.36 UBI/km2). We conclude that wolf and hence caribou populations were not responding in accordance with the outcomes generally predicted by DMAC in our study area because the requisite strong, positive response to fire of deciduous‐browse and alternate‐prey abundance was lacking. As a limiting factor to caribou, DMAC is likely modulated at a macroecological scale by factors such as net primary productivity, a corollary to the general hypothesis that we advance here (i.e., primary productivity hypothesis of DMAC). We caution against managing for caribou based on the presumption of DMAC where the mechanism does not apply, which may include much of boreal caribou range in the north. © 2020 The Wildlife Society.
One‐Step Solvent‐Free Synthesis of Polyglycolic Acid from Sustainable C1 Feedstocks
Authors: Reyhanoglu Yusuf , Kalayci Berkant , Gokturk Ersen
Published: December 2020

Polyglycolic acid (PGA) is an aliphatic biodegradable polyester commonly synthesized through the ring opening polymerization of glycolide using mostly tin (II) octoate catalyst. Previously, a very convenient method for the synthesis of PGA from the cationic alternating copolymerization of formaldehyde (from trioxane) and carbon monoxide (CO) with triflic acid (TfOH) catalyst in dichloromethane (DCM) at 170 °C is described with 92% of yield. The need of using harmful DCM solvent for this polymerization directs to discover solvent‐free polymerization of formaldehyde and CO. Here, one‐step solvent‐free synthesis of PGA from the cationic alternating copolymerization of formaldehyde and CO is presented. Unlike the polymerization carried out in DCM solvent, optimum polymerization in solvent‐free conditions with TfOH catalyst is achieved in 80% of yield at 130 °C. It is considered that utilization of solvent‐free conditions and lower reaction temperatures compared to the previous report provides a more green and economic way of the synthesis of PGA. The method is also extended to copolymerization strategy by adding a minor amount of an epoxide compound to the reaction mixture, and PGA‐based copolymer with improved physical properties (such as solubility and appearance) is obtained in solvent‐free conditions.
Temporal evolution of nerve conduction study abnormalities in anti‐myelin‐associated glycoprotein neuropathy
Authors: Bourque Pierre R. , Masson‐Roy Josée , Warman‐Chardon Jodi , Massie Rami , Melanson Michel , Brooks John , Breiner Ari
Published: December 2020

Background

A distal‐predominant demyelinating symmetric pattern is most frequent in patients with neuropathy associated with anti‐myelin‐associated glycoprotein (MAG) antibodies. The literature however lacks longitudinal data to describe whether this is consistent over time.

Methods

From the Ottawa Neuromuscular Center database, we identified 23 patients with both immunoglobulin M gammopathy and anti‐MAG antibodies. For median, ulnar and fibular motor conduction studies, we analyzed distal latency and amplitude, negative peak duration, terminal latency index (TLI), and conduction velocity. For median, ulnar, sural, and superficial fibular sensory conduction studies, we analyzed distal latency and amplitude. Results were compared for the earliest and the latest data sets.

Results

The mean time interval between the two assessment points was 6.5 years. Median and ulnar motor nerve conduction studies did not show a significant change for any of the parameters tested. There was disproportionate prolongation of median distal motor latency and reduction in TLI, compared to the ulnar nerve. Deep fibular motor conduction studies showed a marked reduction in amplitudes over time. Sensory potentials were recordable in the upper limb in less than 50% at the first study and less than 25% on the most recent study. There was an even larger attrition of recordable sural and superficial fibular sensory potentials.

Conclusions

Our results highlight the stability of median and ulnar motor conduction study results over a mean observation period of 6.5 years. In contrast, lower limb motor and all sensory potentials show a marked trend toward becoming unrecordable.
Pulmonary function testing in patients with neuromuscular disease
Authors: Miller Kristen , Mayer Oscar H.
Published: December 2020

Progressive neuromuscular disease leads to muscle weakness or failure that produces loss of pulmonary function and clinical respiratory morbidity. Tracking pulmonary function in a practical and effective way is very important because it can help identify a stage of disease when a morbidity, such as inadequate airway clearance or respiratory failure, may be present. There are four general categories of pulmonary function outcome measures such as volume, flow, pressure, and gas exchange. These outcome measures have variable precision and accuracy in predicting clinical change, and practicality in performing them relative to age and condition. It is widely recommended to follow multiple measurements longitudinally and create an accurate and timely clinical picture. This manuscript will review the most commonly used and most practical measures for use in clinical practice and how they can help to assess morbidity, disease state, and help optimize patient management.
Preface
Authors: Vaupel James W.
Published: December 2020

The advance of the frontier of survival is documented, verified, and brought to life in this monograph.
Centenarians and Supercentenarians in Japan
Authors: Saito Yasuhiko , Ishii Futoshi , Robine Jean-Marie
Published: December 2020

In this chapter, we use censuses, lists of centenarians, and vital statistics to describe the demography of centenarians, defined as the group of people who are 100 years old or older. We also refer to the group of people between the ages of 105 and 109 as semi-supercentenarians. Finally, we refer to those individuals who reach the age of 110 and beyond as supercentenarians. Although our ability to describe centenarians using these data is currently very limited, censuses and the lists of centenarians can be used to determine the number of people who survive to age 100 or older. Moreover, vital statistics provides the number of deaths, by single year of age and by sex, for those who died above the age of 100 since 1899. Our study examines trends in the highest ages at death for each year between 1963 and 2015, and shows increasing trends during this period. Using the number of deaths and applying the extinct cohort method, we estimate the level of mortality of people aged 100 or older, as well as trends in mortality. We observe decreasing trends in mortality levels among people who have reached very high ages, even as mortality continues to increase with age until very high ages.
Semi-supercentenarians in the United States
Authors: Kestenbaum Bert
Published: December 2020

This chapter discusses in detail the procedure followed to identify a 1-in-10 sample of persons born between 1870 and 1899 who resided in the United States at the time of their death at ages 105–109 for men and 108 or 109 for women. We tabulate the characteristics of these “semi-supercentenarians” and offer some observations about the level of their mortality. The procedure for identifying semi-supercentenarians consists of (1) casting a net to find candidates and then (2) determining for which candidates can both date of birth and date of death be validated. The net used to find candidates in the United States is different from the nets typically used in other counties: in the United States we use the file of enrollments in the federal government’s Medicare health insurance program. Some of the information needed for the verification step comes from another administrative file – the Social Security Administration’s file of applications for a new or replacement social security card. Verification of the date of death is accomplished by querying the National Death Index. Dates of birth are verified by using online resources to access the records of several censuses conducted many decades earlier.
Margaret Ann Harvey Neve – 110 Years Old in 1903. The First Documented Female Supercentenarian
Authors: Poulain Michel , Chambre Dany , Jeune Bernard
Published: December 2020

Margaret Ann Harvey was born on 18 May 1792 in St Peter Port, which is the capital city of Guernsey, the second-largest of the Channel Islands; and died there on 4 April 1903 at the reported age of 110. In this contribution, her exceptional age is thoroughly validated. Considering the data collected on her parents and siblings, there is no possibility of an erroneous linkage, as the name of Margaret and Ann appears only once in the birth records, her family’s birth intervals were narrow, and the dates of death of her siblings have been checked. As she did not have children, her name was not found in civil registration records after her marriage in 1823 until her death in 1903. This lack of records might have made it difficult to prove that the person who died at age 110 in 1903 was the same person who married in 1823 at age 30. Fortunately, she was enumerated in six successive censuses from 1851 to 1901, and a comparison of the ages reported in these censuses and her exact ages shows only minor deviations. Moreover, numerous letters and her numerous diaries help us to follow her life during that long period. Upon reaching age 100, she became famous in Guernsey. Thus, there are many photos of her and press articles about her life. These data support the reliability of the reported chronology of her life events, and thus allow us to validate this exceptional case. Accordingly, we can state that Margaret Ann Harvey Neve is the first documented female supercentenarian. As in the case of recently deceased supercentenarian Emma Morano, her life spanned three successive centuries – albeit one century earlier.
Emma Morano – 117 Years and 137 Days
Authors: Jeune Bernard , Poulain Michel
Published: December 2020

Emma Morano was born on 29 November 1899 in a small mountain village in Piemonte, and died on 15 April 2017 in Verbania on Lake Maggiore (100 km north of Milano). She was the daughter of Giovanni Morano, a miner; and Mathilde Bresciani, aged 24, a weaver. She was the first child in the family, and her arrival was followed by the births of seven siblings, four sisters and three brothers, all of whom she all survived. On 16 October 1926, Emma Morano married Giovanni Martinuzzi, but they separated a few years later after the death of their child. For more than 30 years, she worked in a jute factory. She then worked for about 20 years in the kitchen of a Marianist boarding school until she retired at the age of 75. After retirement, she lived in a small two-room apartment. In her final years, her hearing and sight were greatly reduced, but she could recognise faces and could communicate when spoken to loudly. She seemed to remember both past events and more recent ones. She had never been hospitalised, but had been treated for gastrointestinal bleeding and for urinary infections. She took no drugs regularly except laxatives. In the archives of four municipalities in the region, we obtained copies of the death certificates of her parents, the birth certificates of all of her siblings, her marriage certificate, and the birth and death certificates of her child. We found no inconsistences in the documents.
The International Database on Longevity: Data Resource Profile
Authors: Jdanov Dmitri A. , Shkolnikov Vladimir M. , Gellers-Barkmann Sigrid
Published: December 2020

Even in countries with very good statistical systems, routine population statistics that cover individuals of very high ages are often problematic, as the proportion of erroneous cases increases sharply with age. The desire to measure human mortality at extreme ages was the main motivation for the establishment of the International Database on Longevity (IDL). The IDL is a uniquely valuable source of information on extreme human longevity. It provides high-quality age-validated individual-level data on the ages of semi-supercentenarians and supercentenarians. Moreover, the IDL is the only database that provides such data without age-ascertainment bias. It obtains its candidates from records of government agencies to ensure that there is no dependency between the probability of being included and age. Candidates who meet strict criteria for the validity of their age (date of their birth) are then included in the IDL. Nevertheless, the IDL does not include exhaustive sets of validated supercentenarians and semi-supercentenarians for any country, because it is nearly impossible to find documents that would allow for the validation of the ages of all of the individuals on the list. As of August 2017, the IDL has records on 1,304 validated supercentenarians and 18,590 semi-supercentenarians from 15 countries. The first person in the IDL collection who attained age 110 was born in 1852 and died in 1962 in Quebec, while the last person was born in 1906 and attained age 110 in 2016. This chapter introduces the database and explains its purpose and principles. We also describe the data structure and provide an overview of the information available.
Does the Risk of Death Continue to Rise Among Supercentenarians?
Authors: Villavicencio Francisco , Aburto José Manuel
Published: December 2020

A study published in the Society of Actuaries’ 2017 Living to 100 Monograph suggests, in contrast to previous research, that the risk of death after age 110 years increases with age. By fitting a Gompertz model to estimated central death rates for the oldest old, the authors challenge existing theory and empirical research indicating a deceleration of mortality at older ages and the emergence of a plateau. We argue that their results are inconclusive for three reasons: (1) the data selection was arbitrary; (2) the statistical analysis was inappropriate; and (3) the presentation of the results is misleading and inadequate. We therefore claim that the hypothesis that the human force of mortality increases after age 110 has not been proved.
The Human Longevity Record May Hold for Decades: Jeanne Calment’s Extraordinary Record Is Not Evidence for an Upper Limit to Human Lifespan
Authors: Lenart Adam , Aburto José Manuel , Stockmarr Anders , Vaupel James W.
Published: December 2020

Since 1990 Jeanne Louise Calment has held the record for human longevity. She was born on 21 February 1875, became the longest-lived human on 12 May 1990 when she was 115.21 and died on 4 August 1997 at age 122.45 years. In this chapter, we use data available on 25 September 2017 on people who reached age 110, supercentenarians, to address the following questions:

How likely is it that a person has reached age 122.45?

How unlikely is it that Calment’s record has not yet been broken?

How soon might it be broken?

Assuming a constant annual probability of death of 50% after age 110, we found that the probability that a person who survived to age 110 would have lived to 122.45 by 25 September 2017 is 17.1%. Furthermore, we calculated that there was only a 20.3% chance that Calment’s record would have been broken after 1997 but before 2017. Finally, we estimated that there is less than a 50% chance that someone will surpass Calment’s lifespan before 2045. Jeanne Louise Calment’s record is exceptional but not impossible. It does not provide evidence that her lifespan is an upper limit to human lifespans.
RAP Model—Enabling Cross-Layer Analysis and Optimization for System-on-Chip Resilience
Authors: Herkersdorf Andreas , Engel Michael , Glaß Michael , Henkel Jörg , Kleeberger Veit B. , Kühn Johannes M. , Marwedel Peter , Mueller-Gritschneder Daniel , Nassif Sani R. , Rehman Semeen , Rosenstiel Wolfgang , Schlichtmann Ulf , Shafique Muhammad , Teich Jürgen , Wehn Norbert , Weis Christian
Published: December 2020

The Resilience Articulation Point (RAP) model aims to provision a probabilistic fault abstraction and error propagation concept for various forms of variability related faults in deep sub-micron CMOS technologies at the semiconductor material or device levels. RAP assumes that each of such physical faults will eventually manifest as a single- or multi-bit binary signal inversion or out-of-specification delay in a signal transition between bit values. When probabilistic error functions for specific fault origins are known at the bit or signal level, knowledge about the unit of design and its environment allow the transformation of the bit-related error functions into characteristic higher layer representations, such as error functions for data words, finite state machine (FSM) states, IP macro-interfaces, or software variables. Thus, design concerns can be investigated at higher abstraction layers without the necessity to further consider the full details of lower levels of design. This chapter introduces the ideas of RAP based on examples of particle strike, noise and voltage drop induced bit errors in SRAM cells. Furthermore, we show by different examples how probabilistic bit flips are systematically abstracted and propagated towards instruction and data vulnerability at MPSoC architecture level, and how RAP can be applied for dynamic testing and application-level optimizations in an autonomous robot scenario.
Resource Management for Improving Overall Reliability of Multi-Processor Systems-on-Chip
Authors: Ma Yue , Zhou Junlong , Chantem Thidapat , Dick Robert P. , Hu X. Sharon
Published: December 2020

Multi-processor systems on a chip (MPSoCs) are widely deployed in real-time embedded systems. In such systems, soft-error reliability (caused by transient faults) and lifetime reliability (caused by permanent faults) are both imperative design concerns. Most existing work considers only one of the two classes of faults. Unfortunately, techniques that increase one may adversely impact the other. Achieving high overall reliability requires a trade-off of soft-error reliability and lifetime reliability. In this chapter, we first introduce concepts and models associated with the two reliability metrics, then present two techniques that optimize them separately. Finally, we show how to make appropriate trade-offs using two case studies involving “big–little” type MPSoCs and CPU–GPU integrated MPSoCs.
Cross-Layer Resilience Against Soft Errors: Key Insights
Authors: Mueller-Gritschneder Daniel , Cheng Eric , Sharif Uzair , Kleeberger Veit , Bose Pradip , Mitra Subhasish , Schlichtmann Ulf
Published: December 2020

Driven by technology scaling, integrated systems become more susceptible to various causes of random hardware faults such as radiation-induced soft errors. Such soft errors may cause malfunction of the system due to corruption of data or control flow, which may lead to unacceptable risks for life or property in safety-critical applications. Hence, safety-critical systems deploy protection techniques such as hardening and redundancy at different layers of the system stack (circuit, logic, architecture, OS/schedule, compiler, software, algorithm) to improve resiliency against soft errors. Here, cross-layer resilience techniques aim at finding lower cost solutions by providing accurate estimation of soft error resilience combined with a systematic exploration of protection techniques that work collaboratively across the system stack. This chapter demonstrates how to apply the cross-layer resilience principle on custom processors, fixed-hardware processors, accelerators, and SRAM memories (with a focus on soft errors) and presents key insights obtained.
Online Test Strategies and Optimizations for Reliable Reconfigurable Architectures
Authors: Bauer Lars , Zhang Hongyan , Kochte Michael A. , Schneider Eric , Wunderlich Hans-Joachim , Henkel Jörg
Published: December 2020

Runtime/reconfigurable architectures based on Field-Programmable Gate Arrays (FPGAs) are a promising augment to conventional processor architectures such as Central Processing Units (CPUs) and Graphic Processing Units (GPUs). Since the reconfigurable parts are typically manufactured in the latest technology, they may suffer from aging and environmentally induced dependability threats. In this chapter, strategic online test methods for dependable runtime-reconfigurable architectures as well as cross-layer optimizations for high reliability and lifetime are developed. Firstly, two orthogonal online tests are proposed that ensure reliable configuration of the reconfigurable fabric and aid fault detection. Secondly, a novel design method called module diversification is presented that enables self-repair of the system in case of faults caused by degradation effects as well as single-event upsets in the configuration. Thirdly, a novel stress-aware placement method is proposed that aims for slowing down system degradation by aging effects. The combined methods ensure reliable operation across architectural and gate level and allow to prolong the lifetime of dependable runtime-reconfigurable architectures.
Uncertainty-Aware Compositional System-Level Reliability Analysis
Authors: Aliee Hananeh , Glaß Michael , Khosravi Faramarz , Teich Jürgen
Published: December 2020

Continuous technology scaling has increased the susceptibility of today’s electronic devices to manufacturing tolerances and environmental changes. The resulting uncertainty in component reliability can be only approximated or estimated at design time and might propagate to system level. Therefore, uncertainty must be considered to enable the design of robust systems. In this chapter, we propose a methodology for cross-level reliability analysis to tame the ever increasing analysis complexity of contemporary systems under the influence of uncertainties. The presented methodology combines various reliability analysis techniques across different levels of abstraction while providing an explicit modeling of uncertainties. It introduces mechanisms for (a) the composition and decomposition of the system during analysis and (b) converting analysis data between different levels of abstraction through adapters. The developed analysis techniques are integrated in an automatic electronic system-level reliability analysis tool to allow for the evaluation of reliability-increasing techniques and for DSE!. The tool thereby uses meta-heuristic algorithms for optimization and enables the comparison of system implementation candidates with objectives represented by uncertainty distributions.
Soft Error Handling for Embedded Systems using Compiler-OS Interaction
Authors: Engel Michael , Marwedel Peter
Published: December 2020

Advancing semiconductor technologies increasingly fail to provide expected gains in cost and energy reductions due to reaching the physical limits of Moore’s Law and Dennard scaling. Instead, shrinking semiconductor feature sizes increase a circuit’s susceptibility to soft errors. In order to ensure reliable operation, a significant hardware overhead would be required.

The FEHLER project (Flexible Error Handling for Embedded Real-Time Systems) introduces error semantics into the software development process which provide a system with information about the criticality of a given data object to soft errors. Using this information, the overhead required for error correction can be reduced significantly for many applications, since only errors affecting critical data have to be corrected.

In this chapter, the fundamental components of FEHLER that cooperate at design and runtime of an embedded system are presented. These include static compiler analyses and transformations as well as a fault-aware microkernel. Using examples of typical embedded applications, the efficiency of the approach is demonstrated, along with an extension towards approximate computing systems.
Robust Computing for Machine Learning-Based Systems
Authors: Hanif Muhammad Abdullah , Khalid Faiq , Putra Rachmad Vidya Wicaksana , Teimoori Mohammad Taghi , Kriebel Florian , Zhang Jeff (Jun) , Liu Kang , Rehman Semeen , Theocharides Theocharis , Artusi Alessandro , Garg Siddharth , Shafique Muhammad
Published: December 2020

The drive for automation and constant monitoring has led to rapid development in the field of Machine Learning (ML). The high accuracy offered by the state-of-the-art ML algorithms like Deep Neural Networks (DNNs) has paved the way for these algorithms to being used even in the emerging safety-critical applications, e.g., autonomous driving and smart healthcare. However, these applications require assurance about the functionality of the underlying systems/algorithms. Therefore, the robustness of these ML algorithms to different reliability and security threats has to be thoroughly studied and mechanisms/methodologies have to be designed which result in increased inherent resilience of these ML algorithms. Since traditional reliability measures like spatial and temporal redundancy are costly, they may not be feasible for DNN-based ML systems which are already super computer and memory intensive. Hence, new robustness methods for ML systems are required. Towards this, in this chapter, we present our analyses illustrating the impact of different reliability and security vulnerabilities on the accuracy of DNNs. We also discuss techniques that can be employed to design ML algorithms such that they are inherently resilient to reliability and security threats. Towards the end, the chapter provides open research challenges and further research opportunities.
Hardware/Software Codesign for Energy Efficiency and Robustness: From Error-Tolerant Computing to Approximate Computing
Authors: Rahimi Abbas , Gupta Rajesh K.
Published: December 2020

Voltage scaling, as the most important knob for energy efficiency, is limited by leakage and variability. Variability is arisen from various sources including static manufacturing process, dynamic voltage and temperature fluctuations, and temporal changes over time. To address these variations, designers resort to excessive margins. These margins are increasing rapidly and eventually obliterating any gains due to device scaling. As a consequence, reduction of margins in design has become an important research challenge. We demonstrate how to recover part of these margins through hardware/software codesign with examples in many-core GPUs and FPGAs. This naturally leads to a departure from traditional error-tolerant computing to approximate computing.
Reliable CPS Design for Unreliable Hardware Platforms
Authors: Chang Wanli , Narayanaswamy Swaminathan , Pröbstl Alma , Chakraborty Samarjit
Published: December 2020

Today, many battery-operated cyber-physical systems (CPS) ranging from domestic robots, to drones, and electric vehicles are highly software-intensive. The software in such systems involves multiple feedback control loops that implement different functionality. How these control loops are designed is closely related to both the semiconductor aging of the processors on which the software is run and also the aging of the batteries in these systems. For example, sudden acceleration in an electric vehicle can negatively impact the health of the vehicle’s battery. On the other hand, processors age over time and stress, impacting the execution of control algorithms and thus the control performance. With increasing semiconductor scaling, and our increasing reliance on battery-operated devices, these aging effects are of concern for the lifetime of these devices. Traditionally, the design of the control loops focused only on control-theoretic metrics, related to stability and performance (such as peak overshoot or settling time). In this chapter we show that such controller design techniques that are oblivious of the characteristics of the hardware implementation platform dramatically worsen the battery behaviour and violate the safety requirement with processor aging. However, with proper controller design these effects can be mitigated—thereby improving the lifetime of the devices.
Our Perspectives
Authors: Chen Jian-Jia , Henkel Joerg
Published: December 2020

Research and development in the last decades have led to a silicon process that has been expected to become inherently undependable in the near future when migrating towards new technologies. The special priority program (SPP) 1500 funded by the German Research Foundation (Deutsche Forschungsgemeinschaft, DFG) in 2010–2016 and the Variability Expedition funded by the National Science Foundation (NSF) in 2010–2015 made a joint effort to explore design challenges of Power Consumption, Reliability, Interference, and Manufacturability under such a design requirement.
ASTEROID and the Replica-Aware Co-scheduling for Mixed-Criticality
Authors: Rambo Eberle A. , Ernst Rolf
Published: December 2020

The ASTEROID project developed a cross-layer fault-tolerance solution to provide reliable software execution on unreliable hardware under soft errors. The approach is based on replicated software execution with hardware support for error detection that exploits future many-core platforms to increase reliability without resorting to redundancy in hardware. This chapter gives an overview of ASTEROID and then focuses on the performance of replicated execution and the proposed replica-aware co-scheduling for mixed-criticality. The performance of systems with replicated execution strongly depends on the scheduling. Standard schedulers, such as Partitioned Strict Priority Preemptive (SPP) and Time-Division Multiplexing (TDM)-based ones, although widely employed, provide poor performance in face of replicated execution. By exploiting co-scheduling, the replica-aware co-scheduling is able to achieve superior performance.