bluuebunny/crossref_metadata_2025 huggingface dataset:
Proposal for the enhancement of Marzamemi’s underwater heritage through the use of digital methodologies
Authors: Prados-Peña M B , Sáez-Pérez M P , García-López A
Published: November 2020

This article discusses the importance of technology in the enhancement of underwater heritage, using the Wreck of the Church in the coastal area of Marzamemi (Italy) as a case study. This heritage site is under study in the framework of the European research and knowledge transfer project, WARMEST. There is an increasing variety of digital tools that promise to improve people’s experience with heritage sites, to enhance the value of heritage and contribute to the socio-economic development of the territories. A strategy is proposed for Marzamemi underwater heritage site, where communication efforts give potential visitors a sense of the destination that motivates them to choose it and encourage them to talk widely about their experience. To this end, digital tools are a great asset in establishing such a communication strategy to increase information about this heritage on the various websites and social networks related to Marzameni, so that knowledge of Marzameni’s underwater heritage would undoubtedly be enhanced.
Digital survey from drone in archaeology: potentiality, limits, territorial archaeological context and variables
Authors: Pecci Antonio
Published: November 2020

The ease of piloting drones, the increasingly high performance of sensors, range of action and autonomy of the platform in flight, combined with an apparent simplicity of realization of 3D models through modern photogrammetry (based on algorithms of Structure from Motion and techniques of Computer Vision), have created a real boom for use in archeology. The trust placed in these new technologies has not always allowed a careful analysis of the limits of these tools and methodologies. In fact, these technologies are often used badly or not to their full potential, probably due to the absence of a general manual and because they are technologies in constant development. The aim of this paper is the discuss of potentials and limits of the use of drones in the documentation of archaeological sites, which are high dependent by the territorial archaeological context and several variables that will be argued.
The versatility of augmented reality for the enhancement of cultural heritage.
Authors: Gitto Stefania , Geri Francesco
Published: November 2020

All Virtual reality, augmented reality, mixed reality or straight-up video games can now be found in growing numbers within spaces dedicated to culture and the arts. The choice of such tools is trans-forming the traditional museum tour into a multifaceted and interactive experience to the point, in some cases, of flirting with entertainment. From our experience, the role of augmented reality hasn’t been to substitute itself to the « real » tour. On the contrary, AR invites the user to immerse themselves in an animated personal experience enriched with supplementary information. Elaborated with goals and features different from those of virtual reality, AR aims at strengthening direct contact with works of art as much as possible, inciting an active « live » use and a presence “on-site” more than “on-line”. The diversity of three logistical contexts in which we have worked — a large-scale monument, a historical palace and its heterogenous art collection, and finally an archeological complex encompassing a traditional museum and the remains of a Roman amphitheatre — has brought us to reflect upon the functional aspects that come to determine a personalized digital product, as tailored as possible to specific needs. Each of the three apps has permitted a deepening of each of their features in order to meet specific goals targeted by various museum institutions. In this paper we describe these features in more specific terms.
Geomatics for studying historic supply systems: the Grotta degli Animali case study
Authors: Tucci G , Bonora V , Conti A , Fiorini L
Published: November 2020

In the past, it was difficult to exhaustively document gardens and artificial grottoes with traditional manual survey techniques and maybe also for this reason the restoration Charters used to pass over the need of an accurate survey. Currently, high resolution sampling allows to obtain 3-D data acquisition and realistic and metrically accurate representations. However, the quality of a digital model is not validated by automatic measures or likelihood but following rigorous acquisition and processing workflows, which must be described in metadata and paradata. The new survey reveals some aspects of the historic water supply system for a better understanding of the construction of this monument and will be extended to the narrow tunnels included in the retaining wall around the grotto.
The influence of loading, temperature and relative humidity on adhesives for canvas lining
Authors: Poulis J A , Seymour K , Mosleh Y
Published: November 2020

The structural conservation of canvas paintings may require lining, a process in which a secondary canvas is adhered to the reverse of the damaged original canvas to provide additional support. Choosing the optimum adhesive or canvas for lining is challenging. Comprehensive data on thermal and mechanical behaviour of different adhesives to enable the conservator to make informed choices for their treatment purposes is scarce. Hence, in this study, four prevalently used adhesives for lining are chosen and their thermal and mechanical behaviour, such as the glass transition and melting temperatures, static lap shear strength and creep resistance, are compared. Thermal properties of the different adhesives are characterised using differential scanning calorimetry (DSC). Furthermore, the effect of temperature cycles (25, 35, and 45°C at a fixed relative humidity of 48%) on the creep behaviour of lined canvases is evaluated. Lap shear and creep experiments are performed on lined canvas mock-ups. The four adhesives tested are: studio formulations of an animal glue-wheat flour paste, as well as a beeswax-damar resin mixture; a patented formula based on an ethylene vinyl acetate copolymer mixture (BEVA 371 O.F.™); and a mixture of two industrially produced acrylic copolymers (Plextol™ D541 and K360). The results demonstrate the remarkable effect of temperature on the creep behaviour of lined canvases, which can be related to their thermal stability.
Preliminary results on surface treatments on wood
Authors: de Ferri L , Strojecki M , Bertolin C
Published: November 2020

One of the main issues of the international research project SyMBoL - Sustainable Management of Heritage Buildings in a Long-term perspective, is the evaluation of wood mechanical properties. Particularly, pine wood is tested being the main building materials of medieval Norwegian stave churches. Experiments are aimed to assess variations in mechanical properties as a function of environmental conditions. Being wood highly sensitive to RH% changes, pine slices were maintained at 80% RH (4 weeks, 20°C) and successively treated with the materials here discussed on the two main surfaces; afterward, they were left at 30% RH for three weeks. Thus, the loss of water from the samples is supposed to occur only through the lateral surfaces since the chosen sealing materials were selected on the basis of their capability to avoid any penetration of water into the samples. This work represents, indeed, the study carried out to select materials to be applied on the wooden surfaces. Paraloid B72, also coupled with a cellulose sand seal spray, a microcrystalline wax and an epoxy resin were tested. Obtained surfaces were evaluated in term of water repellency (contact angle measurements), uniformity of the surface; penetration of the materials into the wooden structures, colour and water vapor sorption.
European Standards for Archaeological Wood - theoretical background, purpose, and application.
Authors: Fioravanti M. , Spriggs J. , Björdal C. , Gregory D. , Pournou A. , Peacock E.A. , Straetkvern K. , Gelbrich J. , Khoï Tran Q.
Published: November 2020

The successful management of archaeological wood finds from waterlogged sites starts in the planning phase of any excavation. From the moment of exposure, waterlogged wood finds are extremely vulnerable to a range of man-made and natural threats. There is a real risk of losing the artefact if it is not handled and conserved properly. This paper describes the process leading to the creation of CEN TC346 Standards for waterlogged wood, and how they will be applied within archaeological excavations and conservation. These, it is confidently expected, will provide European archaeologists, conservators and archaeological curators clear guidelines and decision-making tools for effectively managing finds of wood from waterlogged sites.
Cyber Physical Manufacturing Metrology
Authors: Majstorovic V D , Stojadinovic S
Published: November 2020

The Cyber Physical Manufacturing Metrology (CP2M) is based on integration of the Cyber Physical Manufacturing (CPM) and connection between Internet of Things (IoT) and Cloud technology (CT). These are high-level methodologies for development of new generation manufacturing metrology systems, which are more intelligent, flexible and self-adaptable. CP2M generates Big Data, horizontally by integration (network of machines/CMMs, processes and sensors) and vertically by control (usually defined over five levels) which should be analytically processed and managed by the CP2M. In this paper was given, a detailed analysis of the current framework of development the CP2M. A brief overview of the concept CP2M research, particularly in Serbia is given as well.
Methodology for improving production flows on an assembly line
Authors: Nitu E L , Gavriluta A C , Belu N , Gavriluta C A
Published: November 2020

Globalization of production and strong competition in the economic environment requires manufacturers from automotive industry to offer their customers a wide range of products, of the best quality and at lower prices. In order to achieve a competitive advantage, the automotive industry must to adapt their production systems to mass customisation, so that they can provide the variety demanded by the customers while limiting their costs and maintaining their profitability. In this context, research to increase the performance of assembly lines is increasingly numerous and use different techniques, as: layout design, mathematic modeling, dynamic simulation, Lean manufacturing etc. This paper presents a methodology for improving production flows on an assembly line, which was developed to provide the designer and manager of assembly lines in the automotive industry with a set of logically related steps and steps that would allow to achieve a high-performance assembly line. The stages and steps of this methodology consist in the use of methods from different fields, such as: layout design, modelling-simulation of production flows, labour study, lean manufacturing, and for their application different techniques and tools are used.
Tool‘s profiling for rotational volumetric deformation-analytical study
Authors: Costin G A , Baroiu N , Teodor V G , Paunoiu V , Oancea N
Published: November 2020

The paper develops in an analytical form an algorithm for the profiling of the active elements of the upper half-die forming which generates by means of plastic rotary volumetric deformation of the frontal teeth. The half die has the revolving axis inclined with respect to the axis of the deformed blank, which rotates around its own axis of symmetry. In the generation process, the generating half die also performs a movement of the blank. The constitutive surfaces of the tooth flanks to be generated are complex surfaces, formed of circular arcs with variable radius and disposed on a conical base surface, on the same axis with the half-die axis. Such teeth are used for front blades in the textile industry or drilling machines which performs, besides the rotational movement of the tool and an alternate rectilinear motion thereof, creating a percussion effect on the work piece. The surfaces of the upper half and the half die teeth may be regarded as reciprocal wrapping surfaces, so that the entire generation process is based on the analytical principles of surface winding. Starting from the constructive shape of the frontal tooth plate, in a classical scheme of the structure of the oscillating motion mechanism of the upper half matrix, the shape of the deformation teeth is determined based on a specific algorithm, based on the general theory of surface winding, and dedicated software products for it.
New developed software for processing and analysing of the cutting forces records verified when machining by modern circle-segment end mills
Authors: Polzer A , Vancura T , Trcka T
Published: November 2020

At present, 5-axis machining is often realized with ball end mills that do not achieve the advantages of the modern circle-segment end mills. In recent studies, these tools have been compared concerning the quality of the machined surfaces, machining times and cutting forces. An essential part of the research was an analysis of the force loading of the used tools. To get accurate data about force acting during the machining process, it was necessary to undergo experimental measuring using a cutting force dynamometer. For a force records analysis, the new software was developed based on the MATLAB platform. Evaluated results obtained by the new software are presented in the paper and compared with recent studies.
Influence of vertical step on forces and dimensional accuracy of SPIF parts – a numerical investigation
Authors: Popp M O , Rusu G P , Oleksik V , Biris C
Published: November 2020

Single point incremental forming (SPIF) is a new flexible sheet metal forming process characterized by low costs and the possibility to produce prototype parts without the need for a specific die. This is one of the reasons why this process is nowadays used for manufacturing of highly customized small series parts. The process involves the usage of a hemispherical punch which gradually deforms the sheet metal blank fixed by two simple clamping rings, by following a path until the final shape of the product is obtained. The aim of this paper is to investigate and analyze the influence of the vertical step over forces involved in the process and obtained geometrical accuracy, which is one of the main drawbacks for large scale implementation of the process. A numerical analysis was carried out through finite element method with different step size for frustrum pyramid shaped parts made from the same material. In this way, the most appropriate vertical step can be chosen for further experimental research in order to obtain the most accurate parts and with as little stress as possible on the equipment involved in the process.
Analysis of the influence of the hydrostatic ball burnishing pressure in the surface hardness and roughness of medium carbon steels
Authors: Fernández-Lucio P , González-Barrio H , Gómez-Escudero G , Pereira O , López de Lacalle L N , Rodríguez A
Published: November 2020

Standing sectors in the industry such as railroad or plastic injection moulds presents many challenges for manufacturing complex components in terms of finishing requirements and mechanical properties. Because of that, hydrostatic ball burnishing is considered an optimal solution since it reduces surface roughness and generates hardened surfaces and compressive residual stresses, increasing the performance and lifespan of this parts in terms of resistance and mechanical fatigue. Additionally, this technology could be integrated directly into the machining centres, what reduces times and dimensional errors arising from mooring changes. Therefore, lead times and production costs can be drastically reduced in comparison with other finishing techniques. The aim of this project is to analyse the use of the ball burnishing process to improve the final quality of medium carbon steel surfaces, minimizing surface roughness and improving hardness. In order to achieve significant results, different working pressures are analysed in terms of surface roughness and hardness in AISI 1045 and AISI P20 steels. The results showed a reduction in roughness parameters of more than 89% for both materials using a pressure of 10 MPa. Moreover, at a pressure of 30 MPa, the surface hardness has been increased by 15% and 34% respectively.
An accurate machine learning calculator for the lithium-graphite system
Authors: Babar Mohammad , Parks Holden L , Houchins Gregory , Viswanathan Venkatasubramanian
Published: November 2020

Machine-learning potentials are accelerating the development of energy materials, especially in identifying phase diagrams and other thermodynamic properties. In this work, we present a neural network potential based on atom-centered symmetry function descriptors to model the energetics of lithium intercalation into graphite. The potential was trained on a dataset of over 9000 diverse lithium–graphite configurations that varied in applied stress and strain, lithium concentration, lithium–carbon and lithium–lithium bond distances, and stacking order to ensure wide sampling of the potential atomic configurations during intercalation. We calculated the energies of these structures using density functional theory (DFT) through the Bayesian error estimation functional with van der Waals correlation exchange-correlation functional, which can accurately describe the van der Waals interactions that are crucial to determining the thermodynamics of this phase space. Bayesian optimization, as implemented in Dragonfly, was used to select optimal set of symmetry function parameters, ultimately resulting in a potential with a prediction error of 8.24 meV atom−1 on unseen test data. The potential can predict energies, structural properties, and elastic constants at an accuracy comparable to other DFT exchange-correlation functionals at a fraction of the computational cost. The accuracy of the potential is also comparable to similar machine-learned potentials describing other systems. We calculate the open circuit voltage with the calculator and find good agreement with experiment, especially in the regime x ≥ 0.3, for x in Li
x
C6. This study further illustrates the power of machine learning potentials, which promises to revolutionize design and optimization of battery materials.
Insulin-promoted mobilization of GLUT4 from a perinuclear storage site requires RAB10
Authors: Brumfield Alexandria , Chaudhary Natasha , Molle Dorothee , Wen Jennifer , Graumann Johannes , McGraw Timothy E.
Published: November 2020

Insulin signaling mobilizes glucose transporter 4 (GLUT4) from the trans-Golgi network (TGN) through the AKT-TBC1D4-RAB10 signaling module. GLUT4 localizes to a region of the TGN responsible for retention and release of ATP7A copper transporter and the sorting of lysosomal enzymes to late endosomes.
Depression, Anxiety, and Self-Directed Violence in Women With Endometriosis: A Retrospective Matched-Cohort Study
Authors: Estes Stephanie J , Huisingh Carrie E , Chiuve Stephanie E , Petruski-Ivleva Natalia , Missmer Stacey A
Published: November 2020

The purpose of this study was to compare the incidence of mental health outcomes in women in the United States with and without documented endometriosis. In a retrospective matched-cohort study using administrative health claims data from Optum’s Clinformatics DataMart from May 1, 2000, through March 31, 2019, women aged 18–50 years with endometriosis (n = 72,677), identified by International Classification of Disease diagnosis codes (revisions 9 or 10), were matched 1:2 on age and calendar time to women without endometriosis (n = 147,251), with a median follow-up of 529 days (interquartile range, 195, 1,164). The rate per 1,000 person-years of anxiety, depression, and self-directed violence among women with endometriosis was 57.1, 47.7, and 0.9, respectively. Comparing women with endometriosis to those without, the adjusted hazard ratios and 95% confidence intervals were 1.38 (1.34, 1.42) for anxiety, 1.48 (1.44, 1.53) for depression, and 2.03 (1.60, 2.58) for self-directed violence. The association with depression was stronger among women younger than 35 years (P for heterogeneity < 0.01). Risk factors for incident depression, anxiety, and self-directed violence among women with endometriosis included endometriosis-related pain symptoms and prevalence of other chronic conditions associated with pain. The identification of risk factors for mental health conditions among women with endometriosis may improve patient-centered disease management.
Urinary Sodium and Potassium, and Risk of Ischemic and Hemorrhagic Stroke (INTERSTROKE): A Case–Control Study
Authors: Judge Conor , O’Donnell Martin J , Hankey Graeme J , Rangarajan Sumathy , Chin Siu Lim , Rao-Melacini Purnima , Ferguson John , Smyth Andrew , Xavier Denis , Lisheng Liu , Zhang Hongye , Lopez-Jaramillo Patricio , Damasceno Albertino , Langhorne Peter , Rosengren Annika , Dans Antonio L , Elsayed Ahmed , Avezum Alvaro , Mondo Charles , Ryglewicz Danuta , Czlonkowska Anna , Pogosova Nana , Weimar Christian , Diaz Rafael , Yusoff Khalid , Yusufali Afzalhussein , Oguz Aytekin , Wang Xingyu , Lanas Fernando , Ogah Okechukwu S , Ogunniyi Adesola , Iversen Helle K , Malaga German , Rumboldt Zvonko , Oveisgharan Shahram , Al Hussain Fawaz , Yusuf Salim
Published: November 2020

BACKGROUND

Although low sodium intake (<2 g/day) and high potassium intake (>3.5 g/day) are proposed as public health interventions to reduce stroke risk, there is uncertainty about the benefit and feasibility of this combined recommendation on prevention of stroke.

METHODS

We obtained random urine samples from 9,275 cases of acute first stroke and 9,726 matched controls from 27 countries and estimated the 24-hour sodium and potassium excretion, a surrogate for intake, using the Tanaka formula. Using multivariable conditional logistic regression, we determined the associations of estimated 24-hour urinary sodium and potassium excretion with stroke and its subtypes.

RESULTS

Compared with an estimated urinary sodium excretion of 2.8–3.5 g/day (reference), higher (>4.26 g/day) (odds ratio [OR] 1.81; 95% confidence interval [CI], 1.65–2.00) and lower (<2.8 g/day) sodium excretion (OR 1.39; 95% CI, 1.26–1.53) were significantly associated with increased risk of stroke. The stroke risk associated with the highest quartile of sodium intake (sodium excretion >4.26 g/day) was significantly greater (P < 0.001) for intracerebral hemorrhage (ICH) (OR 2.38; 95% CI, 1.93–2.92) than for ischemic stroke (OR 1.67; 95% CI, 1.50–1.87). Urinary potassium was inversely and linearly associated with risk of stroke, and stronger for ischemic stroke than ICH (P = 0.026). In an analysis of combined sodium and potassium excretion, the combination of high potassium intake (>1.58 g/day) and moderate sodium intake (2.8–3.5 g/day) was associated with the lowest risk of stroke.

CONCLUSIONS

The association of sodium intake and stroke is J-shaped, with high sodium intake a stronger risk factor for ICH than ischemic stroke. Our data suggest that moderate sodium intake—rather than low sodium intake—combined with high potassium intake may be associated with the lowest risk of stroke and expected to be a more feasible combined dietary target.
Twenty-Five-Year Changes in Office and Ambulatory Blood Pressure: Results From the Coronary Artery Risk Development in Young Adults (CARDIA) Study
Authors: Bundy Joshua D , Jaeger Byron C , Huffman Mark D , Knox Sarah S , Thomas S Justin , Shimbo Daichi , Booth John N , Lewis Cora E , Edwards Lloyd J , Schwartz Joseph E , Muntner Paul
Published: November 2020

BACKGROUND

Blood pressure (BP) measured in the office setting increases from early through later adulthood. However, it is unknown to what extent out-of-office BP derived via ambulatory BP monitoring (ABPM) increases over time, and which participant characteristics and risk factors might contribute to these increases.

METHODS

We assessed 25-year change in office- and ABPM-derived BP across sex, race, diabetes mellitus (DM), and body mass index (BMI) subgroups in the Coronary Artery Risk Development in Young Adults study using multivariable-adjusted linear mixed effects models.

RESULTS

We included 288 participants who underwent ABPM at the Year 5 Exam (mean [SD] age, 25.1 [3.7]; 45.8% men) and 455 participants who underwent ABPM at the Year 30 Exam (mean [SD] age, 49.5 [3.7]; 42.0% men). Office, daytime, and nighttime systolic BP (SBP) increased 12.8 (95% confidence interval [CI], 7.6–17.9), 14.7 (95% CI, 9.7–19.8), and 16.6 (95% CI, 11.4–21.8) mm Hg, respectively, over 25 years. Office SBP increased 6.5 (95% CI, 2.3–10.6) mm Hg more among black compared with white participants. Daytime SBP increased 6.3 (95% CI, 0.2–12.4) mm Hg more among participants with a BMI ≥25 vs. <25 kg/m2. Nighttime SBP increased 4.7 (95% CI, 0.5–8.9) mm Hg more among black compared with white participants, and 17.3 (95% CI, 7.2–27.4) mm Hg more among participants with vs. without DM.

CONCLUSIONS

Office- and ABPM-derived BP increased more from early through middle adulthood among black adults and participants with DM and BMI ≥25 kg/m2.
The Destiny of Multiple Domain Amnesic Mild Cognitive Impairment: Effect of Alternative Neuropsychological Definitions and Their Adjunctive Role in Respect of Memory Impairment
Authors: Piccininni Chiara , Quaranta Davide , Gainotti Guido , Lacidogna Giordano , Guglielmi Valeria , Giovannini Silvia , Marra Camillo
Published: November 2020

Objective

Mild cognitive impairment is the main risk factor of dementia. Previous evidence has claimed that subjects with memory disturbances associated with impairment of other cognitive domains (multiple domain amnesic MCI) are at the highest risk of developing dementia. To date, a shared definition of amnesic MCI multiple domain (aMCI-MD) is still lacking.

Method

163 subjects with aMCI were enrolled and followed-up for 2 years. They underwent a baseline comprehensive neuropsychological battery. The cut-off point for each test was set at 1, 1.5, and 2 SD below the mean obtained in normative studies; aMCI-MD was defined as the occurrence of abnormal scores on at least one, two, or three tests not assessing memory. The Episodic Memory Score (EMS), that measures the severity of memory impairment, was determined. Logistic regressionand Cox’s proportional hazard risk models were carried out. The adjunctive effect of the definitions of aMCI-MD on the severity of memory impairment was assessed.

Results

Fifty-four subjects progressed to dementia. Only restrictive definitions of aMCI-MD (at least three tests below 1.5 SD; at least two tests below 2 SD) predicted conversion to dementia in both logistic regression and survival analysis. None of the conditions showed a significant adjunctive effect on the EMS.

Conclusions

The predictive effect of impairment in tests assessing cognitive domains other than memory depends on its psychometric definition. The use of a restrictive definition would be of some usefulness, but the adjunctive effect of such a definition on an integrated analysis of memory impairment may be questionable.
Flexible habitat choice by aphids exposed to multiple cues reflecting present and future benefits
Authors: Yin Wandong , Xue Qi , Tian Baoliang , Yang Shujian , Li Zhengying , Chen Zhaozhao , Ryan Michael J , Hoffmann Ary A
Published: November 2020

Mothers choose suitable habitats for laying offspring to maximize fitness. Because habitat quality varies in space and time, mothers gather information to choose among available habitats through multiple cues reflecting different aspects of habitat quality at present and in the future. However, it is unclear how females assess and integrate different cues associated with current rewards and future safety to optimize oviposition/larviposition decisions, especially across small spatial scales. Here, we tested the individual and interactive effects of leaf surface, leaf orientation, and leaf bending direction on larviposition site choice and fitness benefits of wheat aphids (Metopolophium dirhodum) within individual leaves. We found that females preferred upper over lower surfaces for gaining current food-related rewards, downward- over upward-facing surfaces for avoiding potential abiotic risks, and sunken over protruding surfaces for avoiding potential biotic risks. When facing conflicting cues during larviposition, females preferred downward-facing/sunken surfaces over upper surfaces, suggesting that females prioritize potential safety at the cost of current rewards during decision making. Most importantly, our combined-cue experiments showed females still assessed secondary cues (i.e., the upper surface) when first-ranked cues (i.e., the downward-facing/sunken surface) are available, even though females only gained relatively small fitness rewards through secondary cues, and females can integrate different cues associated with current rewards and potential safety in a multiplicative way to make flexible and complex larviposition decisions. Overall, our findings provide new insights into how animals collect and process multi-cue information associated with current rewards and potential safety to maximize fitness at small spatial scales.
Target shortage and less explored multiple targeting: hurdles in the development of novel antifungals but overcome/addressed effectively through structural bioinformatics
Authors: Jha Anubhuti , Vimal Archana , Kumar Awanish
Published: November 2020

Billions of people are affected by fungal infection worldwide, which is a major cause of morbidity and mortality in humans. Regardless of development in the field of antifungal therapeutics over the last three decades, multidrug resistance and limited efficacy of available antifungal drugs are very prominent and still a great hurdle in the patient treatment. The current antifungal pipeline is dry, which is needed to be strengthened. Although several strategies have been implemented over time to discover novel promising antifungal leads, but very little emphasis has been given to address the gap of fungal target identification. Undeniably, the need for identifying novel cellular fungal targets is as vital as discovering novel antifungal leads and a structural bioinformatics approach could be an effective strategy in this regard. To address the issue, we have performed in silico screening to identify a few potent multiple targeting ligands and their respective antifungal targets. Thus, we offer a perspective on the phenomena of ‘target shortage’ and least explored ‘multiple targeting’ being the most underrated challenges in antifungal drug discovery. ‘Structural bioinformatics’ could be an effective approach in the recognition of new/innovative antifungal target and identification/development of novel antifungal lead molecule aiming multiple molecular targets of the fungal pathogen.
Pathogenic gene prediction based on network embedding
Authors: Liu Yang , Guo Yuchen , Liu Xiaoyan , Wang Chunyu , Guo Maozu
Published: November 2020

In disease research, the study of gene–disease correlation has always been an important topic. With the emergence of large-scale connected data sets in biology, we use known correlations between the entities, which may be from different sets, to build a biological heterogeneous network and propose a new network embedded representation algorithm to calculate the correlation between disease and genes, using the correlation score to predict pathogenic genes. Then, we conduct several experiments to compare our method to other state-of-the-art methods. The results reveal that our method achieves better performance than the traditional methods.
The impact of structural bioinformatics tools and resources on SARS-CoV-2 research and therapeutic strategies
Authors: Waman Vaishali P , Sen Neeladri , Varadi Mihaly , Daina Antoine , Wodak Shoshana J , Zoete Vincent , Velankar Sameer , Orengo Christine
Published: November 2020

SARS-CoV-2 is the causative agent of COVID-19, the ongoing global pandemic. It has posed a worldwide challenge to human health as no effective treatment is currently available to combat the disease. Its severity has led to unprecedented collaborative initiatives for therapeutic solutions against COVID-19. Studies resorting to structure-based drug design for COVID-19 are plethoric and show good promise. Structural biology provides key insights into 3D structures, critical residues/mutations in SARS-CoV-2 proteins, implicated in infectivity, molecular recognition and susceptibility to a broad range of host species. The detailed understanding of viral proteins and their complexes with host receptors and candidate epitope/lead compounds is the key to developing a structure-guided therapeutic design.

Since the discovery of SARS-CoV-2, several structures of its proteins have been determined experimentally at an unprecedented speed and deposited in the Protein Data Bank. Further, specialized structural bioinformatics tools and resources have been developed for theoretical models, data on protein dynamics from computer simulations, impact of variants/mutations and molecular therapeutics.

Here, we provide an overview of ongoing efforts on developing structural bioinformatics tools and resources for COVID-19 research. We also discuss the impact of these resources and structure-based studies, to understand various aspects of SARS-CoV-2 infection and therapeutic development. These include (i) understanding differences between SARS-CoV-2 and SARS-CoV, leading to increased infectivity of SARS-CoV-2, (ii) deciphering key residues in the SARS-CoV-2 involved in receptor–antibody recognition, (iii) analysis of variants in host proteins that affect host susceptibility to infection and (iv) analyses facilitating structure-based drug and vaccine design against SARS-CoV-2.
Deep inverse reinforcement learning for structural evolution of small molecules
Authors: Agyemang Brighter , Wu Wei-Ping , Addo Daniel , Kpiebaareh Michael Y , Nanor Ebenezer , Roland Haruna Charles
Published: November 2020

The size and quality of chemical libraries to the drug discovery pipeline are crucial for developing new drugs or repurposing existing drugs. Existing techniques such as combinatorial organic synthesis and high-throughput screening usually make the process extraordinarily tough and complicated since the search space of synthetically feasible drugs is exorbitantly huge. While reinforcement learning has been mostly exploited in the literature for generating novel compounds, the requirement of designing a reward function that succinctly represents the learning objective could prove daunting in certain complex domains. Generative adversarial network-based methods also mostly discard the discriminator after training and could be hard to train. In this study, we propose a framework for training a compound generator and learn a transferable reward function based on the entropy maximization inverse reinforcement learning (IRL) paradigm. We show from our experiments that the IRL route offers a rational alternative for generating chemical compounds in domains where reward function engineering may be less appealing or impossible while data exhibiting the desired objective is readily available.
ARBitR: an overlap-aware genome assembly scaffolder for linked reads
Authors: Hiltunen Markus , Ryberg Martin , Johannesson Hanna
Published: November 2020

Linked genomic sequencing reads contain information that can be used to join sequences together into scaffolds in draft genome assemblies. Existing software for this purpose performs the scaffolding by joining sequences with a gap between them, not considering potential overlaps of contigs. We developed ARBitR to create scaffolds where overlaps are taken into account and show that it can accurately recreate regions where draft assemblies are broken.

Availability and implementation

ARBitR is written and implemented in Python3 for Unix-based operative systems. All source code is available at https://github.com/markhilt/ARBitR under the GNU General Public License v3.

Supplementary information

Supplementary data are available at Bioinformatics online.
eMPRess: a systematic cophylogeny reconciliation tool
Authors: Santichaivekin Santi , Yang Qing , Liu Jingyi , Mawhorter Ross , Jiang Justin , Wesley Trenton , Wu Yi-Chieh , Libeskind-Hadas Ran
Published: November 2020

We describe eMPRess, a software program for phylogenetic tree reconciliation under the duplication-transfer-loss model that systematically addresses the problems of choosing event costs and selecting representative solutions, enabling users to make more robust inferences.

Availability and implementation

eMPRess is freely available at http://www.cs.hmc.edu/empress.

Supplementary information

Supplementary data are available at Bioinformatics online.
An iterative approach to detect pleiotropy and perform Mendelian Randomization analysis using GWAS summary statistics
Authors: Zhu Xiaofeng , Li Xiaoyin , Xu Rong , Wang Tao
Published: November 2020

Motivation

The overall association evidence of a genetic variant with multiple traits can be evaluated by cross-phenotype association analysis using summary statistics from genome-wide association studies. Further dissecting the association pathways from a variant to multiple traits is important to understand the biological causal relationships among complex traits.

Results

Here, we introduce a flexible and computationally efficient Iterative Mendelian Randomization and Pleiotropy (IMRP) approach to simultaneously search for horizontal pleiotropic variants and estimate causal effect. Extensive simulations and real data applications suggest that IMRP has similar or better performance than existing Mendelian Randomization methods for both causal effect estimation and pleiotropic variant detection. The developed pleiotropy test is further extended to detect colocalization for multiple variants at a locus. IMRP will greatly facilitate our understanding of causal relationships underlying complex traits, in particular, when a large number of genetic instrumental variables are used for evaluating multiple traits.

Availability and implementation

The software IMRP is available at https://github.com/XiaofengZhuCase/IMRP. The simulation codes can be downloaded at http://hal.case.edu/∼xxz10/zhu-web/ under the link: MR Simulations software.

Supplementary information

Supplementary data are available at Bioinformatics online.
Depression, dementia and immune dysregulation
Authors: Hayley Shawn , Hakim Antoine M , Albert Paul R
Published: November 2020

Major depression is a prevalent illness that increases the risk of several neurological conditions. These include stroke, cardiovascular disease, and dementia including Alzheimer’s disease. In this review we ask whether certain types of depression and associated loneliness may be a harbinger of cognitive decline and possibly even dementia. We propose that chronic stress and inflammation combine to compromise vascular and brain function. The resulting increases in proinflammatory cytokines and microglial activation drive brain pathology leading to depression and mild cognitive impairment, which may progress to dementia. We present evidence that by treating the inflammatory changes, depression can be reversed in many cases. Importantly, there is evidence that anti-inflammatory and antidepressant treatments may reduce or prevent dementia in people with depression. Thus, we propose a model in which chronic stress and inflammation combine to increase brain permeability and cytokine production. This leads to microglial activation, white matter damage, neuronal and glial cell loss. This is first manifest as depression and mild cognitive impairment, but can eventually evolve into dementia. Further research may identify clinical subgroups with inflammatory depression at risk for dementia. It would then be possible to address in clinical trials whether effective treatment of the depression can delay the onset of dementia.
Olfactory Dysfunction Predicts the Development of Depression in Older US Adults
Authors: Eliyan Yazan , Wroblewski Kristen E , McClintock Martha K , Pinto Jayant M
Published: November 2020

Neuroanatomic connections link the olfactory and limbic systems potentially explaining an association between olfactory dysfunction and depression. Some previous studies have demonstrated that olfactory dysfunction is associated with increased depressive symptoms. However, these studies were cross-sectional and unable to establish which develops first. We used longitudinal data to determine if impaired odor identification increased subsequent depressive symptoms or vice versa. We assessed olfaction and depression in the National Social Life, Health, and Aging Project, a nationally representative, 15-year longitudinal study of older US adults. Olfaction was measured using a validated odor identification test (Sniffin’ Sticks). Depressive symptoms were measured using a modified version of the validated Center for Epidemiological Studies Depression Scale. Multivariable logistic regression models examined the temporal relationships between developing olfactory dysfunction and depression while accounting for demographics, disease comorbidities, alcohol use, smoking, and cognition. Older adults with olfactory dysfunction had concurrent frequent depressive symptoms (odds ratio [OR] = 1.20, 95% confidence interval [CI] = 1.00–1.43). Among healthy adults at baseline, those who had olfactory dysfunction were more likely to develop frequent depressive symptoms 5 or 10 years later (OR = 2.22, 95% CI = 1.13–4.37). Conversely, those with frequent depressive symptoms at baseline were not more likely to develop olfactory dysfunction 5 or 10 years later. We show for the first time that olfactory dysfunction predicts subsequent development of depression in older US adults. These data support screening for depression in older adults with chemosensory impairment and set the stage for disentangling the relationship between olfaction and depression.
Safety and Efficacy of CR6261 in an Influenza A H1N1 Healthy Human Challenge Model
Authors: Han Alison , Czajkowski Lindsay , Rosas Luz Angela , Cervantes-Medina Adriana , Xiao Yongli , Gouzoulis Monica , Lumbard Keith , Hunsberger Sally , Reed Susan , Athota Rani , Baus Holly Ann , Lwin Amy , Sadoff Jerald , Taubenberger Jeffery K , Memoli Matthew J
Published: November 2020

Background

It is imperative to identify new targets for improved vaccines and therapeutics against influenza. One such target is the relatively conserved stalk region of the influenza A hemagglutinin (HA) surface protein.

Methods

We conducted a randomized, double-blind, phase 2, placebo-controlled trial of a monoclonal antibody that targets the HA stalk (CR6261) in a H1N1pdm09 healthy volunteer human challenge model. A single 50 mg/kg dose of CR6261 was infused 24 hours after challenge. The primary efficacy outcome was area under the curve (AUC) of viral RNA detection over time.

Results

Ninety-one healthy volunteers were randomized and underwent influenza challenge; 49 received CR6261 and 42 received placebo. CR6261 had no statistically significant effect on AUC (AUC, 48.56 log [copies/mL] × days, interquartile range [IQR], 202 vs AUC, 25.53 log [copies/mL] × days, IQR, 155; P = .315) and no clinically significant effect on influenza disease measures including number of symptoms, duration of symptoms, or inFLUenza Patient-Reported Outcome (FLU-PRO) scores. Preexisting anti-NA antibody titers were most predictive of reduced influenza disease. CR6261 reached a mean peak serum concentration of 1 × 106 ng/mL 15 minutes after infusion and a mean peak of 5.97 × 102 ng/mL in the nasal mucosa 2–3 days after infusion.

Conclusions

The results of this study suggest that a monoclonal anti-stalk approach to prevent or treat influenza infection may be limited in efficacy. Future approaches should consider including and evaluating anti-stalk antibodies as part of a multifaceted strategy rather than as a stand-alone therapeutic.

Clinical Trials Registration

NCT02371668.
The Effect of Erwinia amylovora Infection in Apple Saplings and Fruit on the Behavior of Delia platura (Diptera: Anthomyiidae)
Authors: Boucher Matthew , Collins Rowan , Hesler Stephen , Cox Kerik , Loeb Greg
Published: November 2020

The Vector Manipulation Hypothesis (VMH) posits that phytopathogens develop strategies to enhance dissemination by mediating behavior change in insect vectors. The VMH is poorly studied in phytopathogenic bacteria, especially in systems with numerous, occasional vectors. Erwinia amylovora is a bacterial pathogen of pome fruit that produces a bacterial ooze and is mechanically vectored by insects after they feed on ooze. The blossom blight phase of the disease exhibits manipulation of honeybees, leading to enhanced transmission, but whether the same occurs during the shoot blight phase of the disease is unknown. The goal of this study was to evaluate the effect of E. amylovora on the behavior of Delia platura, a fly with a worldwide endemic presence that may transmit E. amylovora. We show that D. platura prefer infected, oozing fruit to uninfected fruit in choice tests and that preference subsides when bacterial ooze is removed from the infected fruit. Flies did not exhibit a preference between infected saplings and uninfected saplings. The volatiles of infected fruit did not attract D. platura, indicating that diseased fruit odor is not responsible for the observed preference for infected fruit. Flies did not differentiate between sapling odors until infected trees had died, at which point they preferred uninfected tree odors. This study supports previous hypotheses suggesting that E. amylovora takes advantage of existing plant–insect interactions, though it is not fully understood how significantly behavioral changes affect transmission. Additional pathosystems with occasional, nonspecific vectors should be studied to further understanding of the VMH.
Mitral annulus disjunction is associated with adverse outcome in Marfan and Loeys–Dietz syndromes
Authors: Chivulescu Monica , Krohg-Sørensen Kirsten , Scheirlynck Esther , Lindberg Beate R , Dejgaard Lars A , Lie Øyvind H , Helle-Valle Thomas , Skjølsvik Eystein T , Estensen Mette E , Edvardsen Thor , Lingaas Per S , Haugaa Kristina H
Published: November 2020

Aims

We aimed to assess the prevalence of mitral annulus disjunction (MAD) and to explore the association with aortic disease and mitral valve surgery in patients with Marfan syndrome (MFS) and Loeys–Dietz syndrome (LDS).

Methods and results

We included consecutive MFS patients fulfilling Revised Ghent Criteria and LDS patients fulfilling Loeys–Dietz Revised Nosology. MAD was identified by echocardiography and was quantified as the longitudinal distance from the ventricular myocardium to the hinge point of the posterior mitral leaflet. Aortic events were defined as aortic dissection or prophylactic aortic surgery. We recorded the need of mitral valve surgery including mitral valve repair or replacement. We included 168 patients (103 with MFS and 65 with LDS). The prevalence of MAD was 41%. MAD was present in all age groups. Aortic events occurred in 112 (67%) patients (27 with dissections and 85 with prophylactic surgical interventions). Patients with MAD were younger at aortic event than those without MAD (log rank = 0.02) Patients with aortic events had greater MAD distance in posterolateral wall [8 (7–10) mm vs. 7 (6–8) mm, P = 0.04]. Mitral events occurred more frequently in patients with MAD (P < 0.001).

Conclusion

MAD was highly prevalent in patients with MFS and LDS. MAD was a marker of severe disease including aortic events at younger age and need of mitral valve surgery. Screening patients with MFS an LDS for MAD may provide prognostic information and may be relevant in planning surgical intervention. Detection of MAD in patients with MFS and LDS may infer closer clinical follow-up from younger age.