bluuebunny/crossref_metadata_2025_split huggingface dataset:
Profiling of intact blood proteins by matrix‐assisted laser desorption/ionization mass spectrometry without the need for freezing – Dried serum spots as future clinical tools for patient screening
Authors: Okai Charles A. , Wölter Manja , Russ Manuela , Koy Cornelia , Petre Brindusa A. , Rath Werner , Pecks Ulrich , Glocker Michael O. 
Published: May 2021

RationaleTo open up new ways for matrix‐assisted laser desorption/ionization mass spectrometry (MALDI‐MS)‐based patient screening, blood serum is the most preferred specimen because of its richness in patho‐physiological information and due to ease of collection. To overcome deleterious freeze/thaw cycles and to reduce high costs for shipping and storage, we sought to develop a procedure which enables MALDI‐MS protein profiling of blood serum proteins without the need for serum freezing.MethodsBlood sera from patients/donors were divided into portions which after pre‐incubation were fast frozen. Thawed aliquots were deposited on filter paper discs and air‐dried at room temperature. Intact serum proteins were eluted with acid‐labile detergent‐containing solutions and were desalted by employing a reversed‐phase bead system. Purified protein solutions were screened by MALDI‐MS using standardized instrument settings.ResultsMALDI mass spectra from protein solutions which were eluted from filter paper discs and desalted showed on average 25 strong ion signals (mass range m/z 6000 to 10,000) from intact serum proteins (apolipoproteins, complement proteins, transthyretin and hemoglobin) and from proteolytic processing products. Semi‐quantitative analysis of three ion pairs: m/z 6433 and 6631, m/z 8205 and 8916, as well as m/z 9275 and 9422, indicated that the mass spectra from either pre‐incubated fast‐frozen serum or pre‐incubated dried serum spot eluted serum contained the same information on protein composition.ConclusionsA workflow that avoids the conventional cold‐chain and yet enables the investigation of intact serum proteins and/or serum proteolysis products by MALDI‐MS profiling was developed. The presented protocol tremendously broadens the clinical application of MALDI‐MS and simultaneously allows a reduction in the costs for storage and shipping of serum samples. This will pave the way for clinical screening of patients also in areas with limited access to health care systems, and/or specialized laboratories.
Statically driven generation of concurrent tests for thread‐safe classes
Authors: Terragni Valerio , Pezzè Mauro 
Published: May 2021

SummaryConcurrency testing is an important activity to expose concurrency faults in thread‐safe classes. A concurrent test for a thread‐safe class is a set of method call sequences that exercise the public interface of the class from multiple threads. Automatically generating fault‐revealing concurrent tests within an affordable time budget is difficult due to the huge search space of possible concurrent tests. In this paper, we present DepCon+, a novel approach that reduces the search space of concurrent tests by leveraging statically computed dependencies among public methods. DepCon+ exploits the intuition that concurrent tests can expose thread‐safety violations that manifest exceptions or deadlocks, only if they exercise some specific method dependencies. DepCon+ provides an efficient way to identify such dependencies by statically analysing the code and relies on the computed dependencies to steer the test generation towards those concurrent tests that exhibit the computed dependencies. We developed a prototype DepCon+ implementation for Java and evaluated the approach on 19 known concurrency faults of thread‐safe classes that lead to thread‐safety violations of either exception or deadlock type. The results presented in this paper show that DepCon+ is more effective than state‐of‐the‐art approaches in exposing the concurrency faults. The search space pruning of DepCon+ dramatically reduces the search space of possible concurrent tests, without missing any thread‐safety violations.
Variation of the response to metal ions and nonsense‐mediated mRNA decay across different Saccharomyces cerevisiae genetic backgrounds
Authors: Wong Angelo , Lam Ernest Moses , Pai Cheryl , Gunderson Annika , Carter Tamar E. , Kebaara Bessie W. 
Published: May 2021

AbstractRegulation of mRNA steady‐state levels is important in controlling gene expression particularly in response to environmental stimuli. This allows cells to rapidly respond to environment changes. The highly conserved nonsense‐mediated mRNA decay (NMD) pathway was initially identified as a pathway that degrades aberrant mRNAs. NMD is now recognized as a pathway with additional functions including precisely regulating the expression of select natural mRNAs. Majority of these natural mRNAs encode fully functional proteins. Regulation of natural mRNAs by NMD is activated by NMD targeting features and environmental cues. Here, we show that Saccharomyces cerevisiae strains from three genetic backgrounds respond differentially to NMD depending on the environmental stimuli. We found that wild type and NMD mutant W303a, BY4741, and RM11‐1a yeast strains respond similarly to copper in the environment but respond differentially to toxic cadmium. Furthermore, the PCA1 alleles encoding different mRNAs from W303a and RM11‐1a strains are regulated similarly by NMD in response to the bio‐metal copper but differentially in response to toxic cadmium.
Enrichment devices for green turtles (Chelonia mydas) reared in captivity programs
Authors: Kanghae Hirun , Thongprajukaew Karun , Inphrom Surasak , Malawa Saowalak , Sandos Patchawadee , Sotong Piyanan , Boonsuk Kullanat 
Published: May 2021

AbstractEnvironmental enrichment supports the well‐being and welfare of captive animals. In the current study, the most suitable form of enrichment device for captive green turtles (Chelonia mydas) was investigated, to support head‐start programs rearing turtles for release into their natural habitat. Fifteen‐day‐old turtles (113–114 g initial weight, n = 75) were randomly distributed into 15 experimental plastic tanks, comprising 5 treatments across three pools of each condition. The turtles in the experimental groups were exposed to four forms of enrichment devices (RS, ring shape; HSQS, hollow square shape; SS, sphere shape; CS, cylinder shape), and their outcomes related to growth, feed utilization, behavior, reduction of injury from conspecifics, and several health parameters were compared to those of a control group. At the end of the 10‐week trial, the growth and feed utilization parameters did not differ across the five groups (p > .05). Of the turtles in the experimental treatments, those in the RS treatment spent more time interacting with the enrichment device, followed by the HSQS group. The percentage of wounds suffered through biting was significantly reduced in the groups exposed to enrichment devices, notably in the turtles exposed to the SS device, followed by the RS device. Significant differences between experimental groups in the specific activities of the major intestinal protein‐digesting enzymes (trypsin and chymotrypsin) were observed. There were no effects noted in the hematological parameters and the main carapace elemental profile as compared to the control treatment. These findings suggest that the RS device is most appropriate in enriching the environment of juvenile green turtles in captivity programs, as well as in zoos or aquaria.
Non-conform Evidence: The Impasse of 1990s Welfare Research
Authors: Kirchhelle Claas 
Published: May 2021

AbstractThis chapter traces the evolution of welfare science and the marketisation of farm animal welfare between 1980 and 2000. During this time, dedicated welfare publications soared, and welfare scientists obtained prestigious university posts. The field’s growth was aided by assurance schemes for animal welfare, which enabled mutually beneficial cooperation between researchers, industry, and NGOs like the RSPCA, whose Freedom Foods Label enjoyed great popularity from 1994 onwards. Assurance schemes shifted welfare politics to the marketplace and generated funds for research and NGOs. They also deescalated frontstage welfare politics by restricting access to corporate- and expert-led discussions about standards and enforcement. Ruth Harrison was sceptical of label claims and welfare’s transition from a moral into an economic value. Meanwhile, researchers continued to disagree on how to define welfare. While most researchers remained confident in their ability to produce meaningful results, animal welfare science entered a prolonged phase of epistemic navel-gazing.
Ruth the Ruthless: Activism, Welfare, and Generational Change
Authors: Kirchhelle Claas 
Published: May 2021

AbstractThis chapter studies the polarisation of 1970s’ British farm animal welfare politics and Ruth Harrison’s career as a full-time public campaigner on the RSPCA Council and as head of her own welfare Trust. Polarised conflicts triggered a professionalisation of RSPCA campaigning. The Society adopted new public pressure tactics, established expert committees, and started commissioning behavioural research. Internal tensions over elite “field sports” also led to the formation of the RSPCA Reform Group. Reform Group members oversaw a streamlining of RSPCA management and leadership. They also popularised animal rights thinking. Ruth Harrison supported opposition to “field sports” and helped trigger the internal crisis that led to the Reform Group’s formation. However, tensions over her role on FAWAC and her focus on gradualist reforms isolated Harrison. Forced to declare bankruptcy after a libel suit against another Council member, Harrison focused on developing her own Farm Animal Care Trust (FACT).
An ERA Acute Model Overview
Authors: Stephansen Cathrine , Bjørgesæter Anders , Brude Odd Willy , Brönner Ute , Rogstad Tonje Waterloo , Kjeilen-Eilertsen Grethe , Libre Jean-Marie , Collin-Hansen Christian 
Published: May 2021

AbstractERA Acute is a model for environmental risk assessment of acute discharges. The calculations follow a common framework for all environmental compartments, whilst maintaining the mechanistic integrity of each compartment and/or VEC group, by using compartment-specific inputs of oil exposure and VEC-specific geographical distribution, vulnerability and recovery-defining parameters/functions. The method allows for using three different levels of detailing in VEC in the exposure and impact calculations. For the highest level of detail, a second step calculates recovery times in three time-factors, as well as the ERA Acute-specific RDF which combines the extent of impact and recovery. The continuous functions of impact and recovery calculations are presented in this chapter, separately for all four compartments. All data are calculated in grid cells, facilitating the use of GIS for viewing inputs and results. The methodology adds up impacts from grid cells to populations, and calculates result statistics from single simulations to scenarios, to multi-scenario DSHAs and cases.
Handling Uncertainty and Sensitivity of ERA Acute Towards Input Parameters
Authors: Stephansen Cathrine , Bjørgesæter Anders , Brude Odd Willy , Brönner Ute , Rogstad Tonje Waterloo , Kjeilen-Eilertsen Grethe , Libre Jean-Marie , Collin-Hansen Christian 
Published: May 2021

AbstractUncertainty evaluation and sensitivity testing of the functions and parameters used in ERA Acute serve two functions. ERA Acute is a deterministic model which is sensitive to the range of values used for the parameters. Parameters have inherent uncertainties as to what their true values are, and functions may have varying strength of knowledge. The individual functions were tested with respect to their sensitivity towards variation of the parameter values using both deterministic and stochastic testing. Based on the testing, an uncertainty scoring system was used to identify and prioritize the most important parameters for reducing uncertainty. Recommendations for handling the uncertainty and securing comparability in spite of uncertainty were set up as a conclusion of the studies.
The coset construction for particles of arbitrary spin
Authors: Landry Michael J. , Sun Guanhao 
Published: May 2021

Abstract
When a Poincaré-invariant system spontaneously breaks continuous internal symmetries, Goldstones’ theorem demands the existence of massless, spin-zero excitations in a one-to-one correspondence with the broken symmetry generators. When a system spontaneously breaks Poincaré symmetry, however, the kinds of excitations that satisfy Goldstone’s theorem can be quite unusual. In particular, they may have any spin and need not be particles or even quasiparticles. The standard coset construction used to formulate effective actions of Goldstones, however, is rather restrictive and is incapable of generating the full spectrum of possibilities allowed by Goldstone’s theorem. We propose a (partial) remedy to this problem by postulating a novel coset construction for systems that spontaneously break Poincaré symmetry. This new construction is capable of generating effective actions with a wide range of Goldstone excitations — including fermionic degrees of freedom — even when all symmetries are bosonic. To demonstrate its utility, we focus on constructing effective actions for point particles of various spins. We recover the known result that a particle of spin s requires an $$ \mathcal{N} $$
N
= 2s supersymmetric worldline reparameterization gauge symmetry, which we implement at the level of the coset construction. In the process, we discover that massless particles require a novel kind of inverse Higgs constraint that bears some resemblance to the dynamical inverse Higgs constraints that appear in certain fermi liquid effective field theories. We then consider particles that, in addition to quantum spin, have finite spatial extent and are free to rotate. We derive a novel action for such particles and find a ‘spin-orbital’ coupling between the intrinsic quantum spin and the physical-rotation degrees of freedom.
Multiple sclerosis is linked to MAPKERK overactivity in microglia
Authors: ten Bosch George J. A. , Bolk Jolande , ‘t Hart Bert A. , Laman Jon D. 
Published: May 2021

AbstractReassessment of published observations in patients with multiple sclerosis (MS) suggests a microglial malfunction due to inappropriate (over)activity of the mitogen-activated protein kinase pathway ERK (MAPKERK). These observations regard biochemistry as well as epigenetics, and all indicate involvement of this pathway. Recent preclinical research on neurodegeneration already pointed towards a role of MAPK pathways, in particular MAPKERK. This is important as microglia with overactive MAPK have been identified to disturb local oligodendrocytes which can lead to locoregional demyelination, hallmark of MS. This constitutes a new concept on pathophysiology of MS, besides the prevailing view, i.e., autoimmunity. Acknowledged risk factors for MS, such as EBV infection, hypovitaminosis D, and smoking, all downregulate MAPKERKnegative feedback phosphatases that normally regulate MAPKERKactivity. Consequently, these factors may contribute to inappropriate MAPKERKoveractivity, and thereby to neurodegeneration. Also, MAPKERKoveractivity in microglia, as a factor in the pathophysiology of MS, could explain ongoing neurodegeneration in MS patients despite optimized immunosuppressive or immunomodulatory treatment. Currently, for these patients with progressive disease, no effective treatment exists. In such refractory MS, targeting the cause of overactive MAPKERKin microglia merits further investigation as this phenomenon may imply a novel treatment approach.
The Burden of Disease and Pathology at a Rapidly Expanding Tertiary Paediatric Surgical Unit in South Africa
Authors: Zanini A. , Maistry N. , Brisighelli G. , Gabler T. , Harrison D. , Westgarth‐Taylor C. , Withers A. , Loveland J. , Patel N. 
Published: May 2021

AbstractBackgroundThe precise burden of paediatric surgical care in South Africa is unknown. In the absence of epidemiological data, hospital‐based study is a first step to gauge the burden and profile of paediatric surgical disease. We aim to describe the profile of pathology, pattern of referrals, and complications of paediatric surgical care at Chris Hani Baragwanath Academic Hospital (CHBAH).MethodsA 1‐year retrospective record review for the period 3/1/2019 to 1/1/2020 was conducted by evaluation of the morbidity and mortality databases of the Department of Paediatric Surgery (DPS). Number of admissions, consultations, complications, and surgeries performed were analysed and classified.ResultsA total of 11,932 unique patient encounters occurred. Emergencies (79%, 1841/2329) accounted for the majority of admissions. Trauma accounted for 49% (896/1841) of emergency admissions. Elective surgery constituted 52% (1202/2316) and emergency surgery 48% (1114/2316) of all procedures performed. The emergency department (55%, 1271/2329), outpatients department (19%, 447/2329), and peripheral hospitals (16%, 378/2329) were the source of the majority of admissions. A complication rate of 9% (208/2316) was observed.ConclusionThe high‐volume subspecialist environment at CHBAH presents the ideal environment for delivery of specialist paediatric surgical services and training. Injury prevention, optimal use of existing resources, and additional physical, human and financial resources are required to meet the existing and predicted future burden of paediatric surgical disease.
BRAF-V600E-Testung beim metastasierten kolorektalen Karzinom und neue, chemotherapiefreie Therapieoptionen
Authors: Hummel Michael , Hegewisch-Becker Susanna , Neumann Jens , Vogel Arndt 
Published: May 2021

ZusammenfassungDie Therapie des metastasierten kolorektalen Karzinoms (mKRK) hat in den letzten 25 Jahren tief greifende Veränderungen erfahren. Auf die Zulassung neuerer Chemotherapeutika folgten ab 2005 die ersten zielgerichteten Therapien, die sich gegen den epidermalen Wachstumsfaktorrezeptor (EGFR) bzw. gegen Rezeptoren vaskulärer endothelialer Wachstumsfaktoren (VEGFR) richteten. Mit der fortschreitenden molekularen Charakterisierung des mKRK in den letzten 10 Jahren und der Einteilung der Erkrankung in 4 Konsensus-Subtypen zeichnet sich weiterer Wandel ab, unter anderem durch Einführung speziell entwickelter Proteinkinaseinhibitoren wie auch Immuncheckpoint-Inhibitoren in den Therapiealgorithmus.Eine angepasste molekularpathologische Testung ist heute für eine leitliniengerechte Behandlung von mKRK-Patienten unabdingbar. Neben der RAS-Testung als Voraussetzung für die Therapieentscheidung bezüglich Cetuximab und Panitumumab ist die BRAF-Testung äußerst relevant, um – im Falle des Nachweises einer BRAF-V600E-Mutation – eine Therapieentscheidung zugunsten der neu zugelassenen, chemotherapiefreien Kombination aus dem BRAF-Inhibitor Encorafenib und Cetuximab treffen zu können. Eine erweiterte Diagnostik sollte auch die Genominstabilität (Mikrosatelliten-Instabilität) einbeziehen. Insgesamt müssen immer mehr molekulare Alterationen simultan untersucht werden, sodass sich zunehmend die Verwendung des fokussierten Next Generation Sequencing empfiehlt.Diese Übersichtsarbeit beschreibt die prognostische Relevanz der BRAF-Testung im Rahmen der molekularpathologischen Diagnostik des mKRK, stellt neue Therapieoptionen zur Behandlung BRAF-mutierter mKRK-Patienten vor und erläutert, welche modernen DNA-analytischen und immunohistochemischen Verfahren zur BRAF-Diagnostik von mKRK-Patienten zur Verfügung stehen.
Die Mikroarchitektur des Pankreaskarzinoms aus Sicht des Pathologen und des Radiologen
Authors: Mayer Philipp , Gaida Matthias M. 
Published: May 2021

ZusammenfassungDie diagnostische Radiologie ist gemeinsam mit der diagnostischen Pathologie eines der klinisch-morphologischen Fächer, welche in unterschiedlicher makroskopischer bzw. mikroskopischer Auflösung zur Detektion, Charakterisierung sowie zum Ausbreitungsmuster eines Tumors führen. Die klinischen Disziplinen sind oft voneinander getrennt, wenngleich es vor allem in klinischen Tumorboards immer stärkere Verzahnungen gibt. Am Beispiel des Pankreaskarzinoms sind die Korrelationen radiologischer und pathologischer Diagnostik dargestellt.
David Hilbert and the foundations of the theory of plane area
Authors: Giovannini Eduardo N. 
Published: May 2021

AbstractThis paper provides a detailed study of David Hilbert’s axiomatization of the theory of plane area, in the classical monograph Foundation of Geometry (1899). On the one hand, we offer a precise contextualization of this theory by considering it against its nineteenth-century geometrical background. Specifically, we examine some crucial steps in the emergence of the modern theory of geometrical equivalence. On the other hand, we analyze from a more conceptual perspective the significance of Hilbert’s theory of area for the foundational program pursued in Foundations. We argue that this theory played a fundamental role in the general attempt to provide a new independent basis for Euclidean geometry. Furthermore, we contend that our examination proves relevant for understanding the requirement of “purity of the method” in the tradition of modern synthetic geometry.
ANN-aided incremental multiscale-remodelling-based finite strain poroelasticity
Authors: Dehghani Hamidreza , Zilian Andreas 
Published: May 2021

AbstractMechanical modelling of poroelastic media under finite strain is usually carried out via phenomenological models neglecting complex micro-macro scales interdependency. One reason is that the mathematical two-scale analysis is only straightforward assuming infinitesimal strain theory. Exploiting the potential of ANNs for fast and reliable upscaling and localisation procedures, we propose an incremental numerical approach that considers rearrangement of the cell properties based on its current deformation, which leads to the remodelling of the macroscopic model after each time increment. This computational framework is valid for finite strain and large deformation problems while it ensures infinitesimal strain increments within time steps. The full effects of the interdependency between the properties and response of macro and micro scales are considered for the first time providing more accurate predictive analysis of fluid-saturated porous media which is studied via a numerical consolidation example. Furthermore, the (nonlinear) deviation from Darcy’s law is captured in fluid filtration numerical analyses. Finally, the brain tissue mechanical response under uniaxial cyclic test is simulated and studied.