bluuebunny/crossref_metadata_2025_split huggingface dataset:
AlphaFold accurately predicts distinct conformations based on the oligomeric state of a de novo designed protein
Authors: Cummins Matthew C. , Jacobs Tim M. , Teets Frank D. , DiMaio Frank , Tripathy Ashutosh , Kuhlman Brian 
Published: June 2022

AbstractUsing the molecular modeling program Rosetta, we designed a de novo protein, called SEWN0.1, which binds the heterotrimeric G protein Gαq. The design is helical, well‐folded, and primarily monomeric in solution at a concentration of 10 μM. However, when we solved the crystal structure of SEWN0.1 at 1.9 Å, we observed a dimer in a conformation incompatible with binding Gαq. Unintentionally, we had designed a protein that adopts alternate conformations depending on its oligomeric state. Recently, there has been tremendous progress in the field of protein structure prediction as new methods in artificial intelligence have been used to predict structures with high accuracy. We were curious if the structure prediction method AlphaFold could predict the structure of SEWN0.1 and if the prediction depended on oligomeric state. When AlphaFold was used to predict the structure of monomeric SEWN0.1, it produced a model that resembles the Rosetta design model and is compatible with binding Gαq, but when used to predict the structure of a dimer, it predicted a conformation that closely resembles the SEWN0.1 crystal structure. AlphaFold's ability to predict multiple conformations for a single protein sequence should be useful for engineering protein switches.
Identification of 121 variants of honey bee Vitellogenin protein sequences with structural differences at functional sites
Authors: Leipart Vilde , Ludvigsen Jane , Kent Matthew , Sandve Simen , To Thu‐Hien , Árnyasi Mariann , Kreibich Claus D. , Dahle Bjørn , Amdam Gro V. 
Published: June 2022

AbstractProteins are under selection to maintain central functions and to accommodate needs that arise in ever‐changing environments. The positive selection and neutral drift that preserve functions result in a diversity of protein variants. The amount of diversity differs between proteins: multifunctional or disease‐related proteins tend to have fewer variants than proteins involved in some aspects of immunity. Our work focuses on the extensively studied protein Vitellogenin (Vg), which in honey bees (Apis mellifera) is multifunctional and highly expressed and plays roles in immunity. Yet, almost nothing is known about the natural variation in the coding sequences of this protein or how amino acid‐altering variants might impact structure–function relationships. Here, we map out allelic variation in honey bee Vg using biological samples from 15 countries. The successful barcoded amplicon Nanopore sequencing of 543 bees revealed 121 protein variants, indicating a high level of diversity in Vg. We find that the distribution of non‐synonymous single nucleotide polymorphisms (nsSNPs) differs between protein regions with different functions; domains involved in DNA and protein–protein interactions contain fewer nsSNPs than the protein's lipid binding cavities. We outline how the central functions of the protein can be maintained in different variants and how the variation pattern may inform about selection from pathogens and nutrition.
Nuclear quantum effect and H/D isotope effect in excited state intramolecular proton transfer and electron‐induced intramolecular proton transfer reactions in 8‐hydroxyquinoline
Authors: Udagawa Taro , Hattori Ikumi , Kanematsu Yusuke , Ishimoto Takayoshi , Tachikawa Masanori 
Published: June 2022

AbstractThe optimum exponent () value in 1s Gaussian type function (GTF) was analyzed to develop nuclear basis function for multicomponent quantum mechanics (MC_QM) calculations, in which nuclear quantum effects are directly included, on electronic excited state. We have demonstrated that the general values proposed for MC_QM calculations () on electronic ground state are also useful for the MC_QM calculations on excited state. In addition, we also analyzed the value for the MC_QM calculation of transition state (TS) structures. Although the values for TS structures are smaller than those for energy‐minimum structures, indicating that the nuclear wavefunction becomes more diffusive at TS, H/D isotope effects in TS structures can be adequately analyzed using the values. We have demonstrated that 1s GTF with the value is useful for the MC_QM calculation on not only electronic ground state but also excited states and calculation of TS structures.
A combinatorial proof of Aldous–Broder theorem for general Markov chains
Authors: Fredes Luis , Marckert Jean‐François 
Published: June 2022

AbstractAldous–Broder algorithm is a famous algorithm used to sample a uniform spanning tree of any finite connected graph , but it is more general: given an irreducible and reversible Markov chain on started at , the tree rooted at formed by the first entrance steps in each node (different from the root) has a probability proportional to , where the edges are directed toward . In this article we give proofs of Aldous–Broder theorem in the general case, where the kernel is irreducible but not assumed to be reversible (this generalized version appeared recently in Hu, Lyons, and Tang [5]). We provide two new proofs: an adaptation of the classical argument, which is purely probabilistic, and a new proof based on combinatorial arguments. On the way we introduce a new combinatorial object that we call the golf sequences.
Resilience to climate change‐caused flooding—Metro Vancouver case study
Authors: Simonovic Slobodan P. , Peck Angela 
Published: June 2022

AbstractClimate variability, together with other drivers of global change (like population growth, land‐use change, etc.), is affecting the management of floods. Traditional approaches are no longer sufficient to address the increased pressures that areas vulnerable to flooding are facing. A paradigm shift from flood risk reduction to flood resilience‐building strategies is required. An analytical framework is developed to help quantify, compare, and visualize dynamic resilience to flooding to address some shortcomings in current resilience assessment research. The proposed methodological framework for flood resilience combines physical, economic, engineering, health, and social spatio‐temporal impacts and adaptive capacities of flood‐affected systems. To capture the dynamic spatio‐temporal characteristics of resilience and gauge the effectiveness of potential climate change adaptation options, a flood resilience simulation tool (FRST) is developed to use the analytical framework. The FRST is applied to a case study in Metro Vancouver, British Columbia, Canada. The simulation model focuses on the impacts of climate change‐influenced riverine flooding and sea‐level rise. Simulation results suggest that various adaptation options, such as access to emergency funding, mobile hospital services, and managed retreat can all help to increase resilience to flooding. Results also suggest that, at a regional scale, Metro Vancouver is rather resilient to climate change‐influenced flood hazards.
Construction of a pH‐Mediated Single‐Molecule Switch with a Nanopore‐DNA Complex
Authors: Hu Wei‐Hu , Zhou Ke , Liu Lei , Wu Hai‐Chen 
Published: June 2022

AbstractA molecular switch is one of the simplest examples of artificial molecular machines. Even so, the development of molecular switches is still at its very early stage. Currently, building single‐molecule switches mostly rely on the molecular junction technique, but many of their performance characteristics are device‐dependent. Here, a pH‐mediated single‐molecule switch based on the combination of an α‐hemolysin (αHL) nanopore and a hexacyclen‐modified DNA strand is developed. The single‐stranded DNA is suspended inside an αHL through biotin‐streptavidin linkage and the hexacyclen‐modified nucleobase interacts with amino acid residues at positions 111, 113, and 147 to cause current oscillations. Distinct current transitions are observed when pH is tuned back and forth in the range of 3.0–7.4, with a typical “up” level when pH > 6.5 and a “down” level when pH < 4.5. This nanopore‐DNA complex possesses membrane‐bound advantages and may find applications in single‐cell studies where pH could be readily tuned to control ON‐OFF functions.
A preliminary evaluation of microbial water quality in the irrigation pond
Authors: Zeki Sibel 
Published: June 2022

AbstractThis study aimed to determine the microbial water quality of Imrahor Pond by enumerating the coliform bacteria levels in the area. Water samples were collected biweekly from the surface and bottom waters at seven points in the pond. Samples were analyzed for total coliforms, Escherichia coli, physicochemical parameters (water temperature, conductivity, pH, turbidity, dissolved oxygen, nitrate) and 1‐day rainfall. The average values of TC and E. coli were 1487.4 and 36.3 MPN/100 ml, respectively. TC concentrations/physicochemical parameters were met at least 2nd class water quality class and E. coli results were met “guideline value” (E. coli < 250 MPN/100 ml) of national regulation. Overall, among measured physicochemical parameters, rainfall had the strongest positive correlation (r = 0.377 for total coliforms and r = 0.466 for E. coli, p < 0.05) with both indicators, indicted that surface runoff due to rainfall is the main factor which effects microbial water quality in the study area. This study demonstrated the preliminary microbial water quality results (TC and E. coli) in the Imrahor Pond and can serve as a basis for developing more precise water quality monitoring and management studies in the future.Practitioner points

Prevalence of TC and E. coli in the surface and bottom waters of Imrahor Pond were investigated for the first time.
Imrahor Pond was met guideline value of national regulations based on E. coli concentrations, in the study period.
Surface runoff after rainfall was the main environmental factor which influenced the microbial water quality of the pond.
Improving Education: A Global Perspective
Authors: Püsküllüoğlu Mirosława 
Published: June 2022

AbstractImproving education is an important issue in oncology in order to assure better care for our patients and provide support for oncologists’ community. This chapter has been written by a former student of the Master Online Advanced Oncology program at the University of Ulm, a MSc graduate in Clinical Education at the University of Edinburgh, and a specialist in clinical oncology and clinical pharmacology who has been engaged last 12 years in under- and postgraduate education. The first part of the chapter summarizes challenges in oncology education. The second part focuses on practical examples and global perspective guiding the reader through exemplary projects performed by oncologists all over the world.
Improving Patient Care
Authors: Achimaş-Cadariu Patriciu-Andrei 
Published: June 2022

AbstractIn this introduction, I summarize the different contributions presented by alumni and faculty about patient care during the alumni meeting on the tenth anniversary of the inauguration of the Advanced Oncology study programme of the University of Ulm. The chapters represent the diversity of the different authors, being from low-income, middle-income (LMICs) as well as high-income countries (HICs), considering specific aspects of the entire spectrum of cancer care. What unifies them is their drive to improve patient care in their areas of expertise, with the means they have at hand and the skillset they acquired during their professional and educational journeys, frequently taking them from different parts of the globe to other ones. The task at hand, to reduce cancer-related morbidity and mortality, remains, as do the cornerstones of cancer control like primary prevention, screening and early treatment. Therefore, the interruptive force of the COVID-19 pandemic should be acknowledged, and measures must be implemented to prevent further delays in care for patients with cancers.
Essential Elements in Improving Oncology in Low- and Middle-Income Countries (LMICs) and Examples for Their Implementation in Nigeria
Authors: Ntekim Atara 
Published: June 2022

AbstractIn this chapter, I will summarize the major elements contributing to poor cancer disease outcomes in low- and middle-income countries and suggestions on how to address them. Many measures proposed herein involve social work, public education, and only in later stages health-care workforce. Taking the current COVID-19 pandemic as a starting point, launching public health education and vaccination programs together with raising public awareness for lifestyle-driven diseases may prove a turning point in cancer prevention in many low- and middle-income countries. Collaboration with institutions in high-income countries is also advocated. This will assist in supporting upgrade of facilities, training, logistics support, and data acquisition and management as well as funding of essential cancer services.
Improving Clinical Research
Authors: Gemeinder de Moraes Andre A. J. 
Published: June 2022

AbstractIn this chapter, I will briefly introduce you to the research presentations that were given during the tenth anniversary of the inauguration of the Advanced Oncology Study Program of Ulm University, Germany. I will point out the different perspectives on research including my own. The main idea is to relieve the clinicians among you from fear for not doing enough research but rather encouraging you to read the different chapters—we tried to keep them as light as possible—and consider whether you might pursue one or the other avenue, even though you might be residing in a low- or middle-income country like I do. The main point is that bright minds can do research into cancer wherever they are in the world. And they should.
Anchor Sustainability into the Operating Model
Authors: Aichbauer Stefan , Buchhauser Martina , Erben Agnes , Steinert Sven , Tietze Detlef , Wiking Emilia 
Published: June 2022

AbstractYou are not alone. Use the power of industry groups and set standards. Embed and combine best-of-breed solutions to get the most benefits for an efficient, future-proof procurement process.
Early Warning Systems and Their Role in Disaster Risk Reduction
Authors: Šakić Trogrlić Robert , van den Homberg Marc , Budimir Mirianna , McQuistan Colin , Sneddon Alison , Golding Brian 
Published: June 2022

AbstractIn this chapter, we introduce early warning systems (EWS) in the context of disaster risk reduction, including the main components of an EWS, the roles of the main actors and the need for robust evaluation. Management of disaster risks requires that the nature and distribution of risk are understood, including the hazards, and the exposure, vulnerability and capacity of communities at risk. A variety of policy options can be used to reduce and manage risks, and we emphasise the contribution of early warnings, presenting an eight-component framework of people-centred early warning systems which highlights the importance of an integrated and all-society approach. We identify the need for decisions to be evidence-based, for performance monitoring and for dealing with errors and false information. We conclude by identifying gaps in current early warning systems, including in the social components of warning systems and in dealing with multi-hazards, and obstacles to progress, including issues in funding, data availability, and stakeholder engagement.
On the Inclination of a Flying Buttress Arch
Authors: Samper Albert , Martín-Sáiz Rodrigo , Herrera Blas 
Published: June 2022

AbstractHistorically in architecture, the inclination of a flying buttress arch is determined as the amplitude of the angle that spans between the horizontal straight line and the straight line connecting the two ends of the arch’s lower edge. Nonetheless, this inclination does not represent the entire flyer, but at most only its lower edge. Therefore, using techniques based on geometrical and mechanical criteria, applied to twenty flyer arches belonging to twelve flying buttresses from several European Gothic cathedrals, we present a new proposal for a definition of inclination which represents the entire arch.
Sulfavant A as the first synthetic TREM2 ligand discloses a homeostatic response of dendritic cells after receptor engagement
Authors: Gallo Carmela , Manzo Emiliano , Barra Giusi , Fioretto Laura , Ziaco Marcello , Nuzzo Genoveffa , d’Ippolito Giuliana , Ferrera Francesca , Contini Paola , Castiglia Daniela , Angelini Claudia , De Palma Raffaele , Fontana Angelo 
Published: June 2022

Abstract
Objective
The immune response arises from a fine balance of mechanisms that provide for surveillance, tolerance, and elimination of dangers. Sulfavant A (SULF A) is a sulfolipid with a promising adjuvant activity. Here we studied the mechanism of action of SULF A and addressed the identification of its molecular target in human dendritic cells (hDCs).

Methods
Adjuvant effect and immunological response to SULF A were assessed on DCs derived from human donors. In addition to testing various reporter cells, target identification and downstream signalling was supported by a reverse pharmacology approach based on antibody blocking and gene silencing, crosstalk with TLR pathways, use of human allogeneic mixed lymphocyte reaction.

Results
SULF A binds to the Triggering Receptor Expressed on Myeloid cells-2 (TREM2) and initiates an unconventional maturation of hDCs leading to enhanced migration activity and up-regulation of MHC and co-stimulatory molecules without release of conventional cytokines. This response involves the SYK-NFAT axis and is compromised by blockade or gene silencing of TREM2. Activation by SULF A preserved the DC functions to excite the allogeneic T cell response, and increased interleukin-10 release after lipopolysaccharide stimulation.

Conclusion
SULF A is the first synthetic small molecule that binds to TREM2. The receptor engagement drives differentiation of an unprecedented DC phenotype (homeDCs) that contributes to immune homeostasis without compromising lymphocyte activation and immunogenic response. This mechanism fully supports the adjuvant and immunoregulatory activity of SULF A. We also propose that the biological properties of SULF A can be of interest in various physiopathological mechanisms and therapies involving TREM2.
Analytic properties of heat equation solutions and reachable sets
Authors: Strohmaier Alexander , Waters Alden 
Published: June 2022

AbstractThere recently has been some interest in the space of functions on an interval satisfying the heat equation for positive time in the interior of this interval. Such functions were characterised as being analytic on a square with the original interval as its diagonal. In this short note we provide a direct argument that the analogue of this result holds in any dimension. For the heat equation on a bounded Lipschitz domain$$(\Omega \subset \mathbb {R}^{d})$$(Ω⊂Rd)at positive time all solutions are analytically extendable to a geometrically determined subdomain$${\mathcal {E}}(\Omega )$$E(Ω)of$${\mathbb {C}}^d$$Cdcontaining$$(\Omega )$$(Ω). This domain is sharp in the sense that there is no larger domain for which this is true. If$$(\Omega )$$(Ω)is a ball we prove an almost converse of this theorem. Any function that is analytic in an open neighbourhood of$${\mathcal {E}}(\Omega )$$E(Ω)is reachable in the sense that it can be obtained from a solution of the heat equation at positive time. This is based on an analysis of the convergence of heat equation solutions in the complex domain using the boundary layer potential method for the heat equation. The converse theorem is obtained using a Wick rotation into the complex domain that is justified by our results. This gives a simple explanation for the shapes appearing in the one-dimensional analysis of the problem in the literature. It also provides a new short and conceptual proof in that case.
A priori and a posteriori error analysis of the lowest-order NCVEM for second-order linear indefinite elliptic problems
Authors: Carstensen Carsten , Khot Rekha , Pani Amiya K. 
Published: June 2022

AbstractThe nonconforming virtual element method (NCVEM) for the approximation of the weak solution to a general linear second-order non-selfadjoint indefinite elliptic PDE in a polygonal domain $$\Omega $$
Ω
is analyzed under reduced elliptic regularity. The main tool in the a priori error analysis is the connection between the nonconforming virtual element space and the Sobolev space $$H^1_0(\Omega )$$

H
0
1

(
Ω
)

by a right-inverse J of the interpolation operator $$I_h$$

I
h

. The stability of the discrete solution allows for the proof of existence of a unique discrete solution, of a discrete inf-sup estimate and, consequently, for optimal error estimates in the $$H^1$$

H
1

and $$L^2$$

L
2

norms. The explicit residual-based a posteriori error estimate for the NCVEM is reliable and efficient up to the oscillation terms. Numerical experiments on different types of polygonal meshes illustrate the robustness of an error estimator and support the improved convergence rate of an adaptive mesh-refinement in comparison to the uniform mesh-refinement.
Favorable outcome of SARS-CoV-2 infection in pediatric hematology oncology patients during the second and third pandemic waves in Italy: a multicenter analysis from the Infectious Diseases Working Group of the Associazione Italiana di Ematologia e Oncologia Pediatrica (AIEOP)
Authors: Zama Daniele , Baccelli Francesco , Colombini Antonella , Contino Amalia , Calore Elisabetta , Petris Maria Grazia , Meneghello Linda , Mercolini Federico , Lo Vecchio Andrea , Montalto Shana , Meazza Cristina , Barone Angelica , Compagno Francesca , Muggeo Paola , Soncini Elena , Brescia Letizia , Giraldi Eugenia , Giurici Nagua , Mura Rosa Maria , Cellini Monica , Perruccio Katia , Petroni Valeria , La Spina Milena , Ziino Ottavio , Burnelli Roberta , De Santis Raffaella , Mascarin Maurizio , Barretta Valentina , Tridello Gloria , Cesaro Simone 
Published: June 2022

Abstract
COVID-19 has a mild clinical course with low mortality rate in general pediatric population, while variable outcomes have been described in children with cancer. Infectious diseases working party of the AIEOP collected data on the clinical characteristics and outcomes of SARS-CoV-2 infections in pediatric oncology/hematology patients from April 2020 to May 2021, including the second and the third waves of the pandemic in Italy. Factors potentially associated with moderate, severe, or critical COVID-19 were analyzed. Of the 153 SARS-Cov2 infections recorded, 100 were asymptomatic and 53 symptomatic. The course of COVID-19 was mild in 41, moderate in 2, severe in 5, and critical in 5 children. A total of 40.5% of patients were hospitalized, ten requiring oxygen support and 5 admitted to the intensive care unit. Antibiotics and steroids were the most used therapies. No patient died due to SARS-CoV-2 infection. Infections occurring early (< 60 days) after the diagnosis of the underlying disease or after SCT were associated to moderate, severe, and critical disease compared to infections occurring late (> 60 days) or during maintenance therapy. In the patients on active chemotherapy, 59% withdrew the treatment for a median of 15 days. SARS-CoV-2 presented a favorable outcome in children with cancer in Italy during the pandemic. Modification of therapy represents a major concern in this population. Our findings suggest considering regular chemotherapy continuation, particularly in patients on maintenance therapy or infected late after the diagnosis.