bluuebunny/crossref_metadata_2025 huggingface dataset:
Study on the pack rolling process factor of Ti-6Al-4V alloy
Authors: Choi Miseon , Lee Hyunseok
Published: October 2020

Pack rolling method is preferred to conventional rolling method to process thin sheets or foils out of titanium alloys because of their relatively narrow processing window and possible surface contamination during the elevated temperature processing. In this paper, the core sheets of 5mm thick with equiaxed alpha + transformed beta structure were encapsulated in mild steel cover material and hot rolled in a four high reversing hot rolling mill. The following results were obtained; The optimal pack assembly condition and pack rolling process factor were produced. The effect that the difference in deformation resistance of cover material and core material in pack rolling has been considered. The S45C mild steel is the most suitable for the cover material. The cover material is subjected to the same rolling process as the core material when the initial core and total thickness ratio is 0.3. The reduction in pack rolling should be selected in the range of 20% to 25% to produce flat sheet. Tensile properties of the pack rolled sheet are isotropic in both RD and TD rolling direction which meet the requirements of the standard AMS4911.
Stress partitioning in a near-β Titanium alloy induced by elastic and plastic phase anisotropies: experimental and modeling
Authors: PURUSHOTTAM RAJ PUROHIT Ravi raj purohit , LHADI Safaa , GEY Nathalie , CASTELNAU Olivier , RICHETON Thiebaud , GERMAIN Lionel , BERBENNI Stephane
Published: October 2020

The load transfer induced by the elastic and plastic phase anisotropies of a Ti–10V–2Fe–3Al titanium alloy is studied. The microstructure consists in α nodules embedded in elongated β grains. EBSD performed on the alloy shows no crystallographic texture neither for α nor β phase. Tensile tests along the elongation direction, at a strain rate of 2 x 10-3 s-1 give a yield stress of 830 MPa with 13% ductility.

Simulations based on an advanced two-phase polycrystalline elasto-viscoplastic self-consistent (EVPSC) model predict that the β phase first plastifies with a sequential onset of plasticity starting from <110> oriented β grains, then <111> and finally <100> oriented β grains. This leads to a strong load transfer from the β grains to the α nodules whose average behavior remains elastic up to high stresses (~940 MPa). However, additional simulations considering exclusively β grains of specific orientation show that the behavior of α nodules is strongly dependent on the β texture in which they are embedded. Especially, in <001> β grains, which plastify the latest, the model predicts the onset of plasticity in favorably orientated α nodules. Moreover, the orientation spread within the β grains can modify the average plastic behavior of α phase. In future, these results will be compared to data obtained from in-situ High Energy XRD and SEM/EBSD experiments.
Strengthening of Ti-6Al-7Nb alloy by high-pressure torsion processing
Authors: Ashida M. , Chen P. , Tsutsumi Y. , Hanawa T. , Horita Z.
Published: October 2020

A Ti-6Al-7Nb alloy with three different initial microstructures was processed by high-pressure torsion (HPT) and the resultant microstructure and mechanical properties of the alloy after HPT processing were investigated. The microstructure of the as-received alloy was an equiaxed (α+β) microstructure. The rods were subjected to solution treatment and aging (STA) treatment to obtain a bi-modal microstructure consisting of an equiaxed α phase and lamellar α+β phases, and those to solution treatment and quenching (STQ) treatment to obtain a bi-modal microstructure consisting of equiaxed α-phase and acicular α’-phase. Disks were cut from those rods and were processed by HPT under a pressure of 6 GPa. After HPT processing through 20 revolutions, the alloy with each of the three initial microstructures showed ultrafine grains with a size of ~70 nm. The alloy resulted in a higher tensile strength (1350 MPa) in both the bi-modal microstructures than that (1250 MPa) in the alloy with equiaxed α+β microstructure after HPT processing. It was shown that the Ti-6Al-7Nb alloy with the bi-modal microstructure was strengthened more than with the equiaxed α+β microstructure when the alloy was processed by HPT. Furthermore, the alloy with bi-modal microstructure consisting of equiaxed α-phase and acicular α’-phase showed a good balance between the tensile strength (1280 MPa) and the elongation to fracture (22%) after HPT processing through 1 revolution. In summary, therefore, large strength and elongation of the Ti-6Al-7Nb alloy were simultaneously achieved by HPT processing.
Investigation of phase transformation in Fe microalloyed Ti6Al4V alloy during continuous heating process
Authors: Wang Changliang , Li Feng , Ding Can , Chang Hui , Zhou Lian
Published: October 2020

The phase transformation and dilatometric curves in Fe microalloyed Ti6Al4V alloy (Ti6Al4V-Fe) during continuous heating at 1 ℃ /min heating rate had been studied by dilatometer and metallographic methods, and β phase transition temperatures of alloy were obtained. In order to validate the accuracy of these β phase transition temperature and microstructure evolution, the relative phase concentration and the evolution of microstructure which were acquired by cooling after tempering were analyzed by metallographic microscope. The results illuminated that the expansion method was able to accurately measure the β transformation temperature of Ti6Al4V-Fe alloy. The lathy-shaped α phase decreased significantly disappeared in the range of 838℃ to 988℃, and the α→β phase transformation occurred.
Evolution of microstructure and mechanical properties of Ti-based metal-matrix composites during hot deformation
Authors: Zherebtsov S. , Ozerov M. , Klimova M. , Klimenko D. , Sokolovsky V. , Stepanov N.
Published: October 2020

Two Ti-based composites, viz. Ti/TiB and Ti-15Mo/TiB were produced by spark plasma sintering using a Ti-10wt.%TiB2 powder mixture at 1000°C or Ti-14.25(wt.)%Mo-5(wt.)%TiB2 powder mixture at 1400°C, respectively. Specimens of the metal-matrix composites (MMCs) were subjected to uniaxial compression in the temperature range from 500 to 1050°С to determine processing window. Processing maps for both MMCs were constructed and analyzed. Mechanical behavior and microstructure evolution of both MMCs during multiaxial forging (MAF) at 700°C and at a strain rate 10-3 s-1 were studied. The flow stress for the Ti-15Mo/TiB MMC during MAF was ∼2 times higher than that for the Ti/TiB composite. Microstructure evolution during MAF of Ti/TiB MMC was associated with continuous dynamic recrystallization of the titanium matrix and shortening of TiB whiskers by a factor of ~3. The Ti-15Mo/TiB composite microstructure after did not demonstrate the development of recrystallization.
Micromechanical behaviors related to confined deformation in pure titanium
Authors: Li Runguang , Wang Youkang , Liu Xiaojing , Li Shilei , Tan Qing , Liu Wenjun , Fang Xing , Wang Yan-Dong
Published: October 2020

Confined deformation,e.g.mechanical twinning, shear banding, and Lüders banding,etc.was extensively observed in metals and alloys with low stacking-fault energies, especially under complex loadings, governing the mechanical properties. It is often accompanied with gradient microstructures to accommodate the stress concentrations. Understanding the micromechanical behaviors of structural materials having confined deformation is important for evaluating the structural stabilities of engineering components. Synchrotron-based techniques provide powerful tools for multiscale microstructural characterization owing to their good resolution in real/reciprocal space, fast data collection/processing and flexible application scenarios. In this paper, the synchrotron-based high-energy X-ray diffraction (HE-XRD) and microdiffraction (μXRD) techniques in combination with traditional characterization methods are used to reveal the deformational gradient structures/stresses under different loading modes in multiscale. The structure/stress gradients induced by laser shot peening treatment and the deformation twins generated during uniaxial tensile loading in pure titanium were systematically studied by HE-XRD and μXRD, in order to elucidate the accommodating role of the deformational structures subjected to various confined scenarios. The new finding regarding the micromechanical behaviors related to confined deformation contributes to the in-depth understanding of related complex deformation behaviors.
Nano-scale characterisation of tri-modal microstructures in TIMETAL® 575
Authors: Frutos-Myro Enrique , MacLaren Ian , Li Peifeng , Berment-Parr Iain , Thomas Mathew
Published: October 2020

TIMETAL® 575, developed by Titanium Metals Corporation (TIMET), is a high strength forgeable α+β titanium alloy with comparable density, beta transus temperature and processing characteristics to Ti-6Al-4V but with enhanced static and fatigue strength primarily aimed at aero-engine disc or blade applications. Recent research on this alloy has focussed on microstructure evolution as a means to optimise mechanical behaviour and it has been concluded that a solution heat treatment followed by an ageing step yields a resulting “tri-modal” microstructure, consisting of equiaxed primary α and bi-lamellar transformation product containing nano-scale “tertiary alpha” laths, which appear to provide an excellent balance of strength and ductility. The key objective of the work presented here is to characterise this complex nanoscale microstructure in detail at various stages of alloy processing. For that purpose various advanced and recently developed transmission electron microscopy (TEM) techniques have been used. These include alpha and beta phase mapping Precession Electron Diffraction (PED), overall microstructure imaging with conventional BF and DF TEM, distinction of fine phase detail with high angle annular dark field (HAADF) scanning TEM (STEM), and correlation of the nanostructure to the elemental distribution using scanned Electron Energy Loss Spectroscopy (EELS).
Das maturierte Veneninterponat
Authors: Krönung Gerhard
Published: October 2020

Die prothetovenöse Anastomose neigt besonders bei einer nativen Drainagevene zur Entwicklung prothetovenöser Stenosen. Ein zwischengeschaltetes maturiertes Venensegment scheint die Stenoseinzidenz zu reduzieren.
Monitoring der immunsuppressiven Therapie
Authors: Ehren Rasmus , Weber Lutz T.
Published: October 2020

Das therapeutische Drug-Monitoring (TDM) einer immunsuppressiven Therapie kann einen wichtigen Beitrag zur klinischen Einschätzung des Verlaufes und zur Effektivität der Behandlung leisten. Ziel des TDMs sollte die Optimierung der Medikamentendosierung sein, um eine gute Effektivität bei minimaler Toxizität zu erreichen. Ein TDM kann pharmakokinetisch, pharmakodynamisch und pharmakogenetisch erfolgen. Näher wird auf die Besonderheiten des TDMs von Mycophenolatmofetil (MMF) und Tacrolimus eingegangen. Des Weiteren werden Grundprinzipien und Einflussfaktoren eines TDMs erläutert.
Digitalisierung jenseits von Science-Fiction
Authors: Hübner Ursula Hertha
Published: October 2020

Wie können intelligente Maschinen Pflegekräfte entlasten? Und wie weit ist die Digitalisierung bereits in der Pflege angekommen? Und wie muss die weiter fortschreitende Technisierung aussehen, damit sie zukunftsfähig ist?
Veranstaltungsankündigung
Authors: Bundschu Marion
Published: October 2020

Der Schulungsort ist das Hotel Seligweiler (Seligweiler 1, 89081 Ulm-Seligweiler). Weitere Informationen zu den Veranstaltungen finden Sie unter www.wbs-ulm.de.
A Rare Case of a CSF Pseudocyst Mimicking a Complex Hepatic Cyst
Authors: Sharma Jatin , Al-Katib Sayf
Published: October 2020

Cerebrospinal fluid (CSF) peritoneal pseudocysts are a rare complication of ventriculoperitoneal shunts. They can manifest with symptoms of shunt malfunction or, more commonly, vague symptoms of abdominal discomfort such as pain or distention. The imaging features of peritoneal CSF pseudocysts may be nonspecific. In this case, we report a peritoneal CSF pseudocyst, which was initially mistaken for a complex hepatic cyst on both ultrasonography and MRI. The correct diagnosis was confirmed with a shuntogram and CT of the abdomen.
Self-reported health and the social body
Authors: Balaj Mirza
Published: October 2020

Since the strong predictive power of self-reported health (SRH) for prospective health and social outcomes has been established, researchers have been in a quest to build a theoretical understanding of this widely used health measure. Current literature based predominantly in a biomedical perspective asserts a linear relationship between physical conditions and perception of health. Discrepancies from this expected relationship are considered an important weakness of SRH. Systematic discrepancies between physical conditions and reporting of SRH have been documented across different socio-economic groups. Evidence identified for educational groups shows that for the same level of health status, lower-educated groups report poorer levels of perceived health. This raised doubts whether it is useful to use SRH to measure social inequalities in health within and between countries. To date, sociologists of health have not engaged in the discussion of reporting heterogeneity in SRH. After reviewing existing evidence, we contend that the discrepancy in SRH reporting across social groups argued to be a weakness of SRH as a health measure is a strength from a sociological perspective. SRH as asocial measure of healthis a better predictor than objective measures of health precisely because it captures the lived experience of the embodied agent.
Copula is an intuitive predicate of consciousness on fulfilment of knowing and judging acts
Authors: Pala Kiran
Published: October 2020

The recent investigations into knowledge and its elements viz facts, skills and objects have become prominent in various subfields of philosophy and other areas like linguistics, cognitive science, neuroscience and artificial intelligence. These investigations have been mainly on understanding the relation between the intentionality and its referential entities to know how they enrich knowledge with their existence. This article starts with an exploration of the fundamental aspects of judgemental sense from the knowledge origins perspective. To explain the consequences of this, I start with reconstructing the notion of categorial intuitions described in Husserl’s sixth Logical Investigations by relating it to ‘knowledge origination’ as an intuitive fulfilment of signifying acts. This offers a relation of perceptual synthesis, operating implicitly among the signifying intentions upon grasping intended objects, in view of language structures such as copulas. This leads to the synthesis of intuitive aspects mainly from the categorial elements for a judgemental sense or thinking and the attitude from the very sphere of perception. The tension between categorial intuitions is understood as foundational acts and founded acts. Husserl’s sixth Logical Investigation describes the notion of passive synthesis, the genesis of categoriality in every realm of sensibility that allows one to formulate the relational role among the ‘act of knowing’ and phenomenological approaches to the judgemental sense. Thus, the investigation focuses on perceptual judgements and categories, which fulfils the judgemental sense of categorial elements and attitude.
Spectral gap of the discrete Laplacian on triangulations
Authors: Chebbi Yassin
Published: October 2020

Our goal in this paper is to find an estimate for the spectral gap of the Laplacian on a two-simplicial complex consisting on a hypergraph of a complete graph. An upper estimate is given by generalizing the Cheeger constant. The lower estimate is obtained from the first non-zero eigenvalue of the discrete Laplacian acting on the functions of certain sub-graphs.
Method to penetrate through the overdense plasma sheath: Mode conversion in nonuniform plasmas with two-temperature electron population
Authors: Zhang Jiahui
Published: October 2020

Electromagnetic wave (EMW) penetration through an overdense plasma sheath is a critical subject in solving the “communication blackout” issue. Based on the numerical electron fluid numerical simulations, the linear mode conversion between EMW and electron acoustic waves (EAWs) was examined in the unmagnetized nonuniform plasma sheath with two-temperature electron population. The first resonant position of EMW in the plasma sheath is crucial to stimulate EAW efficiently, while the second one plays an important role in electromagnetic radiation from EAW. Owing to the mode conversion and EAW propagation, a channel can be opened in the overdense nonuniform plasma sheath for EMW. The transmission efficiency of EMW will be reduced remarkably for lacking a low density region where the mode conversion takes place.
Low-temperature p-type ohmic contact to WSe2 using p+-MoS2/WSe2 van der Waals interface
Authors: Takeyama Kei , Moriya Rai , Watanabe Kenji , Masubuchi Satoru , Taniguchi Takashi , Machida Tomoki
Published: October 2020

This study demonstrates a low-temperature Ohmic contact to WSe2 using a van der Waals (vdW) junction between highly p-doped MoS2 (p+-MoS2) and WSe2. p+-MoS2 exhibits a large work function comparable to that of a well-known metal such as Pt. Owing to its layered crystal structure, p+-MoS2 can easily be exfoliated to obtain atomically flat, freshly cleaved surfaces. Moreover, it is stable in air; therefore, this material can be used as an efficient hole-injection contact to a transition metal dichalcogenide semiconductor like WSe2. An h-BN encapsulated WSe2 field effect transistor (FET) was fabricated, having electrical contacts in the form of two flakes of exfoliated p+-MoS2. The fabricated FET demonstrated Ohmic contact behavior under hole doping between room temperature (295 K) and liquid helium temperature (4.2 K). Further, owing to the low contact resistance of the p+-MoS2/p-WSe2 junction, metal-to-insulator transition of WSe2 was observed upon hole doping, as well as quantum oscillation under the application of a magnetic field. On the basis of the Arrhenius plot, a potential barrier height of ∼41 meV at the p+-MoS2/p-WSe2 junction was determined; we infer that this value is limited by the carrier depletion region of p+-MoS2 at the junction. Overall, this appears to indicate potential high performance of the p+-MoS2/WSe2 vdW Ohmic contact.
Cavity Theory
Authors: Meli Jerome A.
Published: October 2020

Bragg–Gray cavity theory is developed from Gray's original work and expanded to the Spencer–Attix formulation. The need for cavity fluence corrections is discussed. The theory is applied to measurement using parallel plate and cylindrical ionization chambers and the effective point of measurement of cylindrical chambers is demonstrated. Large and small cavities are defined, and Burlin cavity theory outlined.
Differential object marking in P’orhépecha
Authors: Capistrán Garza Alejandra
Published: October 2020

This paper analyzes Differential Object Marking in P’orhépecha, which involves split case and fluid case
alternations. Although this system is sensitive to Animacy and Definiteness, I will show that prominence on these scales does not
account for the distribution of flagging. In fact, in P’orhépecha, the expected prominence effects of these scales are overridden
by certain grammatical properties of the NPs, which explains the obligatory vs. forbidden flagging. The fluid pattern is of
special interest, since even though there is evidence that flagging is used as a device to codify definiteness/specificity, higher
and lower ranked objects on the definiteness scale may be (un)flagged. This peculiar behavior is explained by two facts: (a)
definite/specific descriptions may, and in some instances must, be unflagged when the context of use guarantees the intended
referential interpretation of the NP; and (b) lower ranked objects may be flagged only when their referents exhibit discourse
salience.
Lysine acetylation of cytoskeletal proteins: Emergence of an actin code
Authors: A Mu , Latario Casey J. , Pickrell Laura E. , Higgs Henry N.
Published: October 2020

Reversible lysine acetylation of nuclear proteins such as histones is a long-established important regulatory mechanism for chromatin remodeling and transcription. In the cytoplasm, acetylation of a number of cytoskeletal proteins, including tubulin, cortactin, and the formin mDia2, regulates both cytoskeletal assembly and stability. More recently, acetylation of actin itself was revealed to regulate cytoplasmic actin polymerization through the formin INF2, with downstream effects on ER-to-mitochondrial calcium transfer, mitochondrial fission, and vesicle transport. This finding raises the possibility that actin acetylation, along with other post-translational modifications to actin, might constitute an “actin code,” similar to the “histone code” or “tubulin code,” controlling functional shifts to these central cellular proteins. Given the multiple roles of actin in nuclear functions, its modifications might also have important roles in gene expression.
Enhanced electrochemical performance of solution-processed single-wall carbon nanotube reinforced polyvinyl alcohol nanocomposite synthesized via solution-cast method
Authors: Islam Muhammad Rakibul , Pias S M Nazmus Shakib , Alam Rabeya Binta , Khondaker Saiful I
Published: October 2020

Polyvinyl alcohol/surfactant-free single-walled carbon nanotube (PVA/SF-SWNT) nanocomposites were synthesized by a facile solution-cast technique. The effect of SF-SWNT on the structural, surface-morphological, mechanical, electrical, and electrochemical properties of the nanocomposite was studied. The surface morphology and Fourier Transform Infrared Spectroscopy demonstrate an increased degree of interaction between PVA and SF-SWNT resulting in improved mechanical strength of the nanocomposite. Incorporation of SF-SWNT was found to improve the DC electrical conductivity by almost five orders of magnitude. Furthermore, the effect of SWNT on the electrochemical properties of the nanocomposite was also studied. The PVA/SF-SWNT composite exhibits specific capacitance as high as 26.4 F g−1 at a current density 0.5 mA g−1, which is four times higher than that of PVA (6.1 F g−1). The impedance spectroscopy analysis reveals that the incorporation of SWNT reduces the charge transfer resistance of the nanocomposites resulting in better capacitive performance.
Accurate generation of attolitre droplets for directly printing gold nanoparticles from solution through confined reaction
Authors: Huang Yayu , Fang Fei , Chen Feifei , Cui Xian , Sun Jialin , Zhuang Daming , Wei Jinquan
Published: October 2020

Small droplets exist in nature widely and have attractive applications. Although there are some well-established techniques to produce small droplets, it is still a substantial challenge to generate and measure the volume of ultrafine droplets down to attolitres (aL) precisely. Here, we accurately generate ultrafine droplets in attolitre scale by an electrohydrodynamic jet method. By superimposing a low frequency pulse over a static electric field, the volumes of the ultrafine droplets are accurately controlled from 1 to 5 aL with the best accuracy of 0.3 aL and coefficient of variations less than 25%. Gold nanoparticles are deposited on substrate directly from the ultrafine droplets of HAuCl4/H2O solution through a confined reaction in a reducing environment. The gold nanoparticles exhibit highly sensitive and reproductive in surface-enhanced Raman scattering.
DeepCDR: a hybrid graph convolutional network for predicting cancer drug response
Authors: Liu Qiao , Hu Zhiqiang , Jiang Rui , Zhou Mu
Published: October 2020

Motivation

Accurate prediction of cancer drug response (CDR) is challenging due to the uncertainty of drug efficacy and heterogeneity of cancer patients. Strong evidences have implicated the high dependence of CDR on tumor genomic and transcriptomic profiles of individual patients. Precise identification of CDR is crucial in both guiding anti-cancer drug design and understanding cancer biology.

Results

In this study, we present DeepCDR which integrates multi-omics profiles of cancer cells and explores intrinsic chemical structures of drugs for predicting CDR. Specifically, DeepCDR is a hybrid graph convolutional network consisting of a uniform graph convolutional network and multiple subnetworks. Unlike prior studies modeling hand-crafted features of drugs, DeepCDR automatically learns the latent representation of topological structures among atoms and bonds of drugs. Extensive experiments showed that DeepCDR outperformed state-of-the-art methods in both classification and regression settings under various data settings. We also evaluated the contribution of different types of omics profiles for assessing drug response. Furthermore, we provided an exploratory strategy for identifying potential cancer-associated genes concerning specific cancer types. Our results highlighted the predictive power of DeepCDR and its potential translational value in guiding disease-specific drug design.

Availability and implementation

DeepCDR is freely available at https://github.com/kimmo1019/DeepCDR.

Supplementary information

Supplementary data are available at Bioinformatics online.
Genetic risk for Alzheimer’s disease influences neuropathology via multiple biological pathways
Authors: Hannon Eilis , Shireby Gemma L , Brookes Keeley , Attems Johannes , Sims Rebecca , Cairns Nigel J , Love Seth , Thomas Alan J , Morgan Kevin , Francis Paul T , Mill Jonathan
Published: October 2020

Alzheimer’s disease is a highly heritable, common neurodegenerative disease characterized neuropathologically by the accumulation of β-amyloid plaques and tau-containing neurofibrillary tangles. In addition to the well-established risk associated with the APOE locus, there has been considerable success in identifying additional genetic variants associated with Alzheimer’s disease. Major challenges in understanding how genetic risk influences the development of Alzheimer’s disease are clinical and neuropathological heterogeneity, and the high level of accompanying comorbidities. We report a multimodal analysis integrating longitudinal clinical and cognitive assessment with neuropathological data collected as part of the Brains for Dementia Research study to understand how genetic risk factors for Alzheimer’s disease influence the development of neuropathology and clinical performance. Six hundred and ninety-three donors in the Brains for Dementia Research cohort with genetic data, semi-quantitative neuropathology measurements, cognitive assessments and established diagnostic criteria were included in this study. We tested the association of APOE genotype and Alzheimer’s disease polygenic risk score—a quantitative measure of genetic burden—with survival, four common neuropathological features in Alzheimer’s disease brains (neurofibrillary tangles, β-amyloid plaques, Lewy bodies and transactive response DNA-binding protein 43 proteinopathy), clinical status (clinical dementia rating) and cognitive performance (Mini-Mental State Exam, Montreal Cognitive Assessment). The APOE ε4 allele was significantly associated with younger age of death in the Brains for Dementia Research cohort. Our analyses of neuropathology highlighted two independent pathways from APOE ε4, one where β-amyloid accumulation co-occurs with the development of tauopathy, and a second characterized by direct effects on tauopathy independent of β-amyloidosis. Although we also detected association between APOE ε4 and dementia status and cognitive performance, these were all mediated by tauopathy, highlighting that they are a consequence of the neuropathological changes. Analyses of polygenic risk score identified associations with tauopathy and β-amyloidosis, which appeared to have both shared and unique contributions, suggesting that different genetic variants associated with Alzheimer’s disease affect different features of neuropathology to different degrees. Taken together, our results provide insight into how genetic risk for Alzheimer’s disease influences both the clinical and pathological features of dementia, increasing our understanding about the interplay between APOE genotype and other genetic risk factors.
Antifungal Susceptibility Does Not Correlate With Fungal Clearance or Survival in AIDS-Associated Cryptococcal Meningitis
Authors: O’Connor Lucy , Van Anh Duong , Chau Tran Thi Hong , Chau Nguyen Van Vinh , Huong Lan Nguyen Phu , Wolbers Marcel , Day Jeremy N
Published: October 2020

We investigated the value of susceptibility testing in predicting response in AIDS-associated cryptococcal meningitis using clinical isolates from a randomized controlled trial of antifungal treatment (amphotericin monotherapy, amphotericin with flucytosine, or amphotericin with fluconazole). We found no correlation between antifungal susceptibility and either early or late survival, or fungal clearance.
Circular RNA Sequencing of Maternal Platelets: A Novel Tool for the Identification of Pregnancy-Specific Biomarkers
Authors: Oudejans Cees , Manders Vera , Visser Allerdien , Keijser Remco , Min Naomi , Poutsma Ankie , Mulders Joyce , van den Berkmortel Tarah , Wigman Di-Jan , Blanken Britt , Jongejan Aldo , Pajkrt Eva , de Boer Marjon , Sistermans Erik A , Sie Daoud , Best Myron G , Würdinger Tom , Afink Gijs
Published: October 2020

Background

In the first trimester of pregnancy, the maternal platelet is directly involved in a positive feedback mechanism that facilitates invasion of the extravillous trophoblast into the maternal spiral arteries. Dysfunctional trophoblast invasion with defective deep placentation is primordial in the etiology of the “great obstetrical syndromes.”

Methods

In this proof-of-concept study, using transcriptome analysis of circular RNA (circRNA) following RNA sequencing of maternal platelets, we tested whether pregnancy-specific circRNA markers could be identified in the first trimester of normal pregnancies. Differential transcript expression analysis of circRNAs, as predicted by Accurate CircRNA Finder Suite, CircRNA Identifier (version 2), and Known and Novel Isoform Explorer, was done using thromboSeq.R with variation of multiple settings. Test performance was checked for (a) de novo circRNA identification using the novel platelet-specific Plt-circR4 as a positive control, (b) complete segregation of groups (pregnant vs nonpregnant) after heat map–dendrogram clustering, (c) identification of pregnancy-specific circRNA markers at a false discovery rate (FDR) <0.05, and (d) confirmation of differentially expressed circRNA markers with an FDR <0.05 by an independent method, reverse transcription–quantitative PCR.

Results

Of the differentially expressed circRNAs with P values <0.05, 41 circRNAs were upregulated (logFC >2), and 52 circRNAs were downregulated (logFC less than −2) in first-trimester platelet RNA. Of these, nuclear receptor-interacting protein 1 circRNA covering exons 2 and 3 of the 5′-untranslated region was pregnancy specific with upregulation in first-trimester maternal platelets compared to nonpregnant controls.

Conclusion

CircRNA sequencing of first-trimester maternal platelets permits the identification of novel pregnancy-specific RNA biomarkers. Future use could include the assessment of maternal and fetal well-being.
The protein interaction network of the inherited central nervous system diseases reveals new gene candidates for molecularly unclassified myelin disorders
Authors: Paris Luca , Como Gianluca , Vecchia Ilaria , Pisani Francesco , Ferrara Giovanni
Published: October 2020

Mutations in numerous genes cause the inherited disorders of the white matter in the central nervous system. Interestingly, all these mutations ultimately affect myelin, even though the corresponding proteins are involved in dissimilar functions. To address this system-level issue, we assembled the myelin disease network (MDN), in which each node represents a protein (either the mutated protein or one of its interactors), while each edge linking two nodes represents the physical interaction between the two proteins. Compared with control random networks, the MDN contains more pairs of disease proteins, whose members are linked either directly or via one intermediate protein. Then, we surmised that the interactions might not only cluster proteins into functionally homogenous and distinct modules but also link the modules together. This way, even gene mutations arising in functionally distinct modules might propagate their effects to the other modules, thus accounting for a similar pathological outcome. We found, however, that concerning the function the modules are neither homogeneous nor distinct, mostly because many proteins participate in more than one biological process. Rather, our analysis defines a region of the interactome, where different processes intersect. Finally, we propose that many non-disease proteins in the network might be candidates for molecularly unclassified myelin disorders.
Two ticking time bombs: giant coronary artery aneurysm and abdominal aortic aneurysm in the setting of urgent vascular surgery—a case report
Authors: Schukraft Sara , Carrel Thierry , Togni Mario , Attinger-Toller Adrian
Published: October 2020

Background

Giant coronary artery aneurysms (CAAs) are rare and treatment strategies various, especially in the setting of a concomitant abdominal aortic aneurysm (AAA) which needs urgent repair.

Case summary

A 78-year-old Caucasian male was admitted for evaluation of a rapidly expanding AAA. In addition, computed tomography angiography revealed a 5 x 4 cm giant aneurysm of the right coronary artery. After interdisciplinary discussion, the patient underwent aorto-bi-iliac bypass grafting first. In a second step, CAA was successfully excluded and coronary artery bypass grafting of the right coronary artery was performed.

Discussion

Treatment strategy of CAA and timing of non-cardiac surgery is challenging. In order to minimize the overall risk of rupture interdisciplinary discussion is crucial. In our case, aorto-bi-iliac bypass grafting was safely performed, and the patient underwent successful CAA excision in a second step.
Association between physical performance and cognitive function in older adults across multiple studies: A pooled analysis study
Authors: Handing Elizabeth P , Leng Xiaoyan Iris , Kritchevsky Stephen B , Craft Suzanne
Published: October 2020

Background and Objectives

While several studies have examined the association between cognitive and physical function, the consistency of these associations across functional contexts is unclear. The consistency of association between cognitive and physical function performance was examined at baseline across 17 clinical studies with diverse and heterogeneous conditions such as overweight/obese, sedentary, at risk for a mobility disability, osteoarthritis, low vitamin D, or had signs of cognitive impairment.

Research Design and Methods

Data are from 1,388 adults 50 years and older who completed a cognitive and physical function assessment as part of a research study at the Wake Forest Alzheimer’s Disease Research Center or the Wake Forest Older Americans Independence Center. Linear regression models were used to relate cognitive measures [Mini Mental Status Exam (MMSE), Montreal Cognitive Assessment (MoCA), and the Digit Symbol Substitution Task (DSST)], and physical measures [the Short Physical Performance Battery (SPPB) and hand grip strength] for the whole sample and treat each study as a fixed effect. All models controlled for age, sex, race, and body mass index (BMI).

Results

Overall, there was a significant association between higher scores on the MMSE (per standard deviation) and better physical function performance (SPPB score b= 0.24, p <0.001) and its components (gait speed, chair rise, and standing balance; p’s <0.05). Higher scores on the MoCA produced similar results (SPPB score b= 0.31, p= <0.001) and higher scores on the DSST were also significantly associated with a better SPPB score (b= 0.75, p <0.001). The relationship between DSST and physical function performance demonstrated a stronger magnitude of association compared to the MMSE or MoCA.

Discussion and Implications

Older adults with heterogenous health conditions showed a consistent pattern between better cognitive function and better physical function performance with the strongest association among DSST scores.
The 2020 Historical Research lecture
Authors: Vinen Richard , Langhamer Claire , Siena Kevin
Published: October 2020

The 2020 Historical Research lecture, ‘Writing histories of 2020’, asked how future historians might study and understand the global coronavirus pandemic. The lecture brought together historians with three distinctive perspectives: contemporary history and writing of the very recent past, histories of record keeping and current archive creation, and the history of contagious disease and its human consequences. The three speakers, Richard Vinen, Claire Langhamer and Kevin Siena, provided early responses on future histories of 2020 and how we might best prepare the ground for these studies. This article provides written versions of these commentaries. Common to each of the contributions, and subsequent discussion, is the ongoing challenge and responsibility of thinking historically at a time when history is clearly ‘in the making’.
The role of political leaders in mitigating the risk of mass atrocities: an analysis of Khama, Kaunda and Nyerere
Authors: McLoughlin Stephen
Published: October 2020

This article examines the impact that three political leaders—Seretse Khama, Kenneth Kaunda and Julius Nyerere—had on navigating the long-term risk associated with mass atrocities. While the scholarship on comparative genocide studies has acknowledged the crucial dimension of leadership in the perpetration of such violence, very little is known about the preventive influence of leaders in cases where risk is present. This influence works both ways: the ideas, decisions and policies of political leaders are often the most instrumental factor in effective processes of risk mitigation. Yet to date, there has been no systematic study of the role of leadership in managing and ameliorating risk associated with mass atrocities. Indeed, the more general question of why mass atrocities do not occur is also largely neglected. I argue that these leaders were cognisant of the disruptive potential of tribal, ethnic and religious division; they advocated for inclusive national identities and developed policies that fostered social cohesion; and were effective in creating social and political environments that had an inhibitory effect on structural risk factors associated with atrocity crimes.
Development and Validation of an Inflammatory Bowel Disease Severity Index Using US Administrative Claims Data: A Retrospective Cohort Study
Authors: Chen Grace , Lissoos Trevor , Dieyi Christopher , Null Kyle D
Published: October 2020

Background

Clinical indices to characterize the severity of inflammatory bowel disease (IBD) are widely used in clinical trials and real-world practice. However, there are few validated instruments for assessing IBD severity in administrative claims-based studies.

Methods

Patients (18–89 years) diagnosed with ulcerative colitis (UC) or Crohn’s disease (CD) and receiving ≥1 prescription claim for IBD therapy were identified using administrative claims data from the Optum Clinformatics, IMS PharMetrics, and Truven MarketScan databases (January 1, 2013–September 30, 2017). Regression modeling identified independent predictors of IBD-related hospitalization (inpatient stay or emergency department visit resulting in hospitalization), which were used to develop IBD severity indices. The index was validated against all-cause hospitalization and total cost and IBD-related hospitalization and total cost.

Results

There were 51,767 patients diagnosed with UC (n = 30,993) or CD (n = 20,774) who were initiated treatment with IBD therapy. Independent predictors of IBD-related hospitalization were Charlson Comorbidity Index score >1, anemia, weight loss, intravenous corticosteroid use, prior gastrointestinal-related emergency department visit and hospitalization, and unspecified disease location or more extensive disease. Female sex, renal comorbidities, intestinal fistula, and stricture were additional risk factors for patients with CD, whereas age <40 years was a UC-specific risk factor. Median IBD severity scores were 8 and 13 for UC and CD, respectively, from possible total scores of 51 and 37. Inflammatory bowel disease severity score correlated with significantly higher all-cause hospitalization and cost, all-cause total cost, IBD-related hospitalization cost, and total cost.

Conclusions

These validated UC and CD severity indices can be used to predict IBD-related outcomes using administrative claims databases.
Climate warming and the loss of sea ice: the impact of sea-ice variability on the southeastern Bering Sea pelagic ecosystem
Authors: Hunt George L , Yasumiishi Ellen M , Eisner Lisa B , Stabeno Phyllis J , Decker Mary Beth
Published: October 2020

We investigated relationships among three metrics of sea-ice cover in eight regions of the eastern Bering Sea and the abundance of Calanus copepods, jellyfish medusae, and year-class strength of walleye pollock (Gadus chalcogrammus). In summer, Calanus spp. were more abundant over the middle shelf when sea ice lingered late into spring, and, to a lesser extent, when February sea-ice cover was heavy. Between 1982 and 1999, there were no significant (p ≤ 0.05) relationships between the amount or timing of sea-ice cover and pollock recruitment. However, between 2000 and 2015, pollock year-class strength was positively correlated with sea ice in the outer and middle shelves, with 17 of 24 regressions significant. Pollock year-class strength was best predicted by days with sea-ice cover after February. Pollock recruitment was positively influenced by copepod numbers, particularly in the middle shelf, with r2 values from 0.36 to 0.47. We hypothesize that the Calanus spp. present in the southeastern Bering Sea are primarily Calanus glacialis that have been advected south in association with sea ice. None of our sea-ice metrics explained the variance in jellyfish biomass. Jellyfish biomass in our study area in the pollock age-0 year was not correlated with pollock recruitment 3 years later.
Prevalence of Germline Pathogenic and Likely Pathogenic Variants in Patients With Second Breast Cancers
Authors: Yao K Katharine A , Clifford Jacob , Li Shuwei , LaDuca Holly , Hulick Peter , Gutierrez Stephanie , Black Mary Helen
Published: October 2020

Background

Few studies have examined gene-specific associations with contralateral and/or second breast cancer (SBC).

Methods

The frequency of pathogenic and likely pathogenic (P/LP) variants in clinically actionable genes (BRCA1, BRCA2, PTEN, TP53, CHEK2, CDH1, ATM, PALB2, NBN, and NF1) was compared between women with a primary breast cancer (PBC) and SBC who underwent multigene panel testing at a single diagnostic testing laboratory. Race- and ethnicity-specific logistic regression burden tests adjusted for age at diagnosis of first breast cancer, histology, presence of first- or second-degree relatives with breast cancer, and prior testing for BRCA1/2 genes were used to test for associations with SBC. All statistical tests were 2-sided.

Results

The study was comprised of 75 550 women with PBC and 7728 with SBC. Median time between breast cancers for SBC was 11 (interquartile range = 6–17) years. Restricting to women tested for all actionable genes (n = 60 310), there were 4231 (7.8%) carriers of P/LP variants in actionable genes among the controls (PBC) compared with 652 (11.1%) women with SBC (P< .001). Among Caucasians, exclusive of Ashkenazi Jewish women, those carrying a P/LP variant in a clinically actionable gene were 1.44 (95% confidence interval [CI] = 1.30 to 1.60) times as likely to have SBC than noncarriers, after accounting for potential confounders. Among African American and Hispanic women, a P/LP variant in a clinically actionable gene was 1.88 (95% CI = 1.36 to 2.56) and 1.66 (9% CI = 1.02 to 2.58) times as likely to be associated with SBC, respectively (P < .001 and P = .03).

Conclusion

Women with P/LP variants in breast cancer predisposition genes are more likely to have SBC than noncarriers. Prospective studies are needed confirm these findings.
The Temporal and Geographic Reach of International Humanitarian Law
Authors: Crawford Emily
Published: October 2020

This chapter discusses the geographical and temporal scope of international humanitarian law (IHL). Knowing where and when the provisions of IHL start and cease to apply is vital to ensuring that the rules are respected, and to identifying where other rules of international and domestic law are pertinent or more relevant. As a general rule, IHL applies from the commencement of hostilities, whether such hostilities are international or non-international in character. In international armed conflicts (IACs), situations of belligerent occupation also trigger the applicability of IHL, even if there are no active hostilities. However, there are different thresholds applicable in international and non-international armed conflicts (NIACs). As a general rule, in both IACs and NIACs, IHL will cease to apply when there is a ‘general close of military operations’. Meanwhile, the geographical or spatial scope of IHL depends on what kind of armed conflict is taking place, with different issues arising for both NIACs and IAC.
The effects of subgrid models on the properties of giant molecular clouds in galaxy formation simulations
Authors: Li Hui , Vogelsberger Mark , Marinacci Federico , Sales Laura V , Torrey Paul
Published: October 2020

Recent cosmological hydrodynamical simulations are able to reproduce numerous statistical properties of galaxies that are consistent with observational data. Yet, the adopted subgrid models strongly affect the simulation outcomes, limiting the predictive power of these simulations. In this work, we perform a suite of isolated galactic disc simulations under the SMUGGLE framework and investigate how different subgrid models affect the properties of giant molecular clouds (GMCs). We employ astrodendro, a hierarchical clump-finding algorithm, to identify GMCs in the simulations. We find that different choices of subgrid star formation efficiency, ϵff, and stellar feedback channels, yield dramatically different mass and spatial distributions for the GMC populations. Without feedback, the mass function of GMCs has a shallower power-law slope and extends to higher mass ranges compared to runs with feedback. Moreover, higher ϵff results in faster molecular gas consumption and steeper mass function slopes. Feedback also suppresses power in the two-point correlation function (TPCF) of the spatial distribution of GMCs. Specifically, radiative feedback strongly reduces the TPCF on scales below 0.2 kpc, while supernova feedback reduces power on scales above 0.2 kpc. Finally, runs with higher ϵff exhibit a higher TPCF than runs with lower ϵff, because the dense gas is depleted more efficiently, thereby facilitating the formation of well-structured supernova bubbles. We argue that comparing simulated and observed GMC populations can help better constrain subgrid models in the next generation of galaxy formation simulations.