bluuebunny/crossref_metadata_2025_split huggingface dataset:
Persistence of CRISPR/Cas9 Gene Edited Hematopoietic Stem Cells Following Transplantation: A Systematic Review and Meta-Analysis of Preclinical Studies
Authors: Maganti Harinad B. , Bailey Adrian J. M. , Kirkham Aidan M. , Shorr Risa , Pineault Nicolas , Allan David S. 
Published: March 2021

Abstract
Gene editing blood-derived cells is an attractive approach to cure selected monogenic diseases but remains experimental. A systematic search of preclinical controlled studies is needed to determine the persistence of edited cells following reinfusion. All studies identified in our systematic search (to 20 October 2020) examining the use of CRISPR/Cas9 gene editing in blood-derived cells for transplantation were included. Meta-analysis was performed to determine the engraftment and persistence of gene edited cells. A total of 3538 preclinical studies were identified with 15 published articles meeting eligibility for meta-analysis. These in vivo animal studies examined editing of hemoglobin to correct sickle cell disease (eight studies), inducing resistance to acquired immunodeficiency syndrome (two studies), and six other monogenic disorders (single studies). CRISPR-Cas9 edited hematopoietic stem and progenitor cells demonstrated equivalent early engraftment compared to controls in meta-analysis but persistence of gene-edited cells was reduced at later time points and in secondary transplant recipients. Subgroup analysis in studies targeting the hemoglobin gene revealed a significant reduction in the persistence of gene-edited cells whether homology-directed repair or nonhomologous end-joining were used. No adverse side effects were reported. Significant heterogeneity in study design and outcome reporting was observed and the potential for bias was identified in all studies. CRISPR-Cas9 gene edited cells engraft similarly to unedited hematopoietic cells. Persistence of gene edited cells, however, remains a challenge and improved methods of targeting hematopoietic stem cells are needed. Reducing heterogeneity and potential risk of bias will hasten the development of informative clinical trials.
Experimental study and calculation method on the flexural resistance of reinforced concrete beam strengthened using high strain‐hardening ultra high performance concrete
Authors: Sun Qixin , Liu Chao 
Published: March 2021

AbstractIn this study, the efficiency of using high strain hardening ultra high performance concrete (HSH‐UHPC) on strengthening existing reinforced concrete beams was investigated by experimental and analytical means. First, the HSH‐UHPC constitutive relation was obtained using “Dog‐bone” specimen under uniaxial tensile test. Then three reinforced concrete beams strengthened with HSH‐UHPC layers and one control beam were tested under flexural loading. The midspan deflection, strain distribution, crack propagation and failure mode of the tested beams were described in detail. The tests verified that the middle section of UHPC‐NC composite beam basically conforms to the assumption of plane section. The flexural resistance of composite structure can be greatly improved by installing proper longitudinal reinforcement in UHPC layer. Meanwhile, numerical studies have been conducted on the tested beams using the experimentally obtained constitutive relations. The result shows that the finite element analysis results are consistent with the test results. Finally, a contribution factor for the HSH‐UHPC layer on the flexural resistance of the composite beam was proposed. At the same time, it is found that the contribution efficiency of the HSH‐UHPC to the flexural resistance increases with longitudinal reinforcement ratios in the HSH‐UHPC.
Introducing the Sun and SEPs
Authors: Reames Donald V. 
Published: March 2021

AbstractThe structure of the Sun, with its energy generation and heating, creates convection and differential rotation of the outer solar plasma. This convection and rotation of the ionized plasma generates the solar magnetic field. This field and its variation spawn all of the solar activity: solar active regions, flares, jets, and coronal mass ejections (CMEs). Solar activity provides the origin and environment for both the impulsive and gradual solar energetic particle (SEP) events. This chapter introduces the background environment and basic properties of SEP events, time durations, abundances, and solar cycle variations.
Einleitung
Authors: Schleicher Katharina 
Published: March 2021

ZusammenfassungIm Kontext von Diskursen zur Klimapolitik und einer „Großen Transformation“ hin zu einer ressourcenschonenden Gesellschaft wird immer häufiger auch über die Rolle der Wissenschaft bei diesen Prozessen diskutiert. Eine Forschungsperspektive, die in diesem Zuge entwickelt wurde, ist die sogenannte „transformative Forschung“, bei der Forschende als Katalysatoren Wandel selbst initiieren und unterstützen. Dieser Forschungsansatz wird mithilfe des diskursiven Institutionalismus untersucht. Im einleitenden Kapitel werden die Problemstellung und die Forschungslücke dargestellt, gefolgt von der Forschungsfrage, den Zielen sowie dem Forschungsdesign. Zum Ende dieses Kapitels wird der Aufbau dieses Buches vorgestellt.
Schlussfolgerungen für Theorie und Forschungspraxis: vom veränderten Diskurs zur „Großen Transformation“
Authors: Schleicher Katharina 
Published: March 2021

ZusammenfassungIn diesem Kapitel werden einige der zentralen Thesen des diskursiven Institutionalismus weiterentwickelt. Dabei werden die Voraussetzungen für Transformation und die Definition von Gelegenheitsfenstern für Politikwandel verfeinert sowie neue Erkenntnisse bezüglich des Zusammenhangs zwischen graduellem und transformativem Wandel formuliert. Außerdem werden praktische Handlungsempfehlungen formuliert, wann es mithilfe der transformativen Forschung zu einer erfolgreichen Transformation kommen könnte. Im Hinblick auf die Praxisempfehlungen zeigt sich, dass der Ansatz transformativer Forschung durchaus erfolgversprechend ist, wenn einige Aspekte beachtet werden, so insbesondere die Kooperation mit lokalen Akteur*innen sowie die explizite Kommunikation der alternativen Paradigmen.
Methodisches Vorgehen
Authors: Freigang Sirkka 
Published: March 2021

ZusammenfassungDas Wissen der Zukunft ist vernetzt, dezentral und interdisziplinär. Im Zentrum dieser Herausforderung stehen menschliche Bedürfnisse und nicht technische Möglichkeiten. Die vorliegende Disseration basiert auf einer transdisziplinären Zusammenführung unterschiedlicher Fachdisziplinen und bündelt Erkenntnisse aus Bildungswissenschaften, Informatik und Architektur verbunden mit dem Ziel, Einflussbereiche und Erfolgsfaktoren zu identifizieren, die im Gestaltungsprozess von menschenzentrierten Smart Learning Environments berücksichtigt werden müssen.
Arithmetic of higher-dimensional orbifolds and a mixed Waring problem
Authors: Browning Tim , Yamagishi Shuntaro 
Published: March 2021

AbstractWe study the density of rational points on a higher-dimensional orbifold$$(\mathbb {P}^{n-1},\Delta )$$(Pn-1,Δ)when$$\Delta $$Δis a$$\mathbb {Q}$$Q-divisor involving hyperplanes. This allows us to address a question of Tanimoto about whether the set of rational points on such an orbifold constitutes a thin set. Our approach relies on the Hardy–Littlewood circle method to first study an asymptotic version of Waring’s problem for mixed powers. In doing so we make crucial use of the recent resolution of the main conjecture in Vinogradov’s mean value theorem, due to Bourgain–Demeter–Guth and Wooley.
Adrenal venous sampling in primary hyperaldosteronism: correlation of hormone indices and collimated C-arm CT findings
Authors: Becker L. S. , Hinrichs M. H. , Werncke T. , Dewald C. L. A. , Maschke S. K. , Limbourg F. P. , Ringe K. I. , Hinrichs J. B. , Wacker F. , Meyer B. C. 
Published: March 2021

Abstract
Purpose
To evaluate the feasibility and effect of an approach to adrenal venous sampling (AVS) analysis by combining established selective cortisol and aldosterone indices with the acquisition of a collimated C-arm CT(CACTColl).

Methods
Overall, 107 consecutive patients (45f,62 m; 54 ± 10 years) undergoing 111 AVS procedures without hormonal stimulation from 7/13 to 2/20 in a single institution were retrospectively analysed. Hormone levels were measured in sequential samples of the suspected adrenal veins and right iliac vein, and selectivity indices (SI) computed. Stand-alone SICortisol and/or SIAldosterone ≥ 2.0 as well as SICortisol and/or SIAldosterone ≥ 1.1 combined with positive right-sided CACTColl of the adrenals (n = 80; opacified right adrenal vein) were defined as a successful AVS procedure. Radiation exposure of CACT was measured via dose area product (DAP) and weighed against an age-/weight-matched cohort (n = 66).

Results
Preliminary success rates (SICortisol and/or SIAldosterone ≥ 2.0) were 99.1% (left) and 72.1% (right). These could be significantly increased to a 90.1% success rate on the right, by combining an adjusted SI of 1.1 with a positive CACTColl proving the correct sampling position. Sensitivity for stand-alone collimated CACT (CACTColl) was 0.93, with 74/80 acquired CACTColl confirming selective cannulation by adrenal vein enhancement. Mean DAPColl_CACT measured 2414 ± 958 μGyxm2, while mean DAPFull-FOV_CACT in the matched cohort measured 8766 ± 1956 μGyxm2 (p < 0.001).

Conclusion
Collimated CACT in AVS procedures is feasible and leads to a significant increase in success rates of (right-sided) selective cannulation and may in combination with adapted hormone indices, offer a successful alternative to previously published AVS analysis algorithms with lower radiation exposure compared to a full-FOV CACT.
Photosymbiosis in planktonic foraminifera across the Paleocene–Eocene thermal maximum
Authors: Shaw Jack O. , D'haenens Simon , Thomas Ellen , Norris Richard D. , Lyman Johnnie A. , Bornemann André , Hull Pincelli M. 
Published: March 2021

AbstractUnder stress, corals and foraminifera may eject or consume their algal symbionts (“bleach”), which can increase mortality. How bleaching relates to species viability over warming events is of great interest given current global warming. We use size-specific isotope analyses and abundance counts to examine photosymbiosis and population dynamics of planktonic foraminifera across the Paleocene–Eocene thermal maximum (PETM, ~56 Ma), the most severe Cenozoic global warming event. We find variable responses of photosymbiotic associations across localities and species. In the NE Atlantic (DSDP Site 401) PETM, photosymbiotic clades (acarininids and morozovellids) exhibit collapsed size-δ13C gradients indicative of reduced photosymbiosis, as also observed in Central Pacific (ODP Site 1209) and Southern Ocean (ODP Site 690) acarininids. In contrast, we find no significant loss of size-δ13C gradients on the New Jersey shelf (Millville) or in Central Pacific morozovellids. Unlike modern bleaching-induced mass mortality, populations of photosymbiont-bearing planktonic foraminifera increased in relative abundance during the PETM. Multigenerational adaptive responses, including flexibility in photosymbiont associations and excursion taxon evolution, may have allowed some photosymbiotic foraminifera to thrive. We conclude that deconvolving the effects of biology on isotope composition on a site-by-site basis is vital for environmental reconstructions.
THE PROHIBITION OF TORTURE AND PERSONS LIVING IN POVERTY: FROM THE MARGINS TO THE CENTRE
Authors: Oette Lutz 
Published: March 2021

AbstractTorture of persons living in poverty has traditionally been at the margins of human rights interventions that have primarily focused on political and conflict related torture. This article examines the extent to which the evolving practice of human rights bodies and organisations evidences an emerging paradigm shift. It finds that a combination of a growing body of empirical research, novel approaches by human rights organisations and the work of bodies such as the Subcommittee on Prevention of Torture has increasingly brought into focus the heightened vulnerability to torture resulting from economic marginalisation and discrimination. Drawing on evidence of innovative practices, the article develops the framework for a contextual approach to the interpretation and implementation of States’ obligations under the prohibition of torture that is alive to the realities of systemic violence and the nexus between poverty and torture.
The role of the European small ruminant dairy sector in stabilising global temperatures: lessons from GWP* warming-equivalent emission metrics
Authors: del Prado Agustin , Manzano Pablo , Pardo Guillermo 
Published: March 2021

AbstractRecent calls advocate that a huge reduction in the consumption of animal products (including dairy) is essential to mitigate climate change and stabilise global warming below the 1.5 and 2°C targets. The Paris Agreement states that to stabilise temperatures we must reach a balance between anthropogenic emissions by sources and removals by sinks of greenhouse gases (GHG) in the second half of this century. Consequently, many countries have adopted overall GHG reduction targets (e.g. EU, at least 40% by 2030 compared to 1990). However, using conventional metric-equivalent emissions (CO2-e GWP100) as the basis to account for emissions does not result in capturing the effect on atmospheric warming of changing emission rates from short-lived GHG (e.g. methane: CH4), which are the main source of GHG emissions by small ruminants. This shortcoming could be solved by using warming-equivalent emissions (CO2-we, GWP*), which can accurately link annual GHG emission rates to its warming effect in the atmosphere. In our study, using this GWP* methodology and different modelling approaches, we first examined the historical (1990–2018) contribution of European dairy small ruminant systems to additional atmosphere warming levels and then studied different emission target scenarios for 2100. These scenarios allow us to envision the necessary reduction of GHG emissions from Europe's dairy small ruminants to achieve a stable impact on global temperatures, i.e. to be climatically neutral. Our analysis showed that, using this type of approach, the whole European sheep and goat dairy sector seems not to have contributed to additional warming in the period 1990–2018. Considering each subsector separately, increases in dairy goat production has led to some level of additional warming into the atmosphere, but these have been compensated by larger emission reductions in the dairy sheep sector. The estimations of warming for future scenarios suggest that to achieve climate neutrality, understood as not adding additional warming to the atmosphere, modest GHG reductions of sheep and goat GHG would be required (e.g. via feed additives). This reduction would be even lower if potential soil organic carbon (SOC) from associated pastures is considered.
Conservation and natural resource management: where are all the women?
Authors: James Robyn , Gibbs Bridget , Whitford Laura , Leisher Craig , Konia Ruth , Butt Nathalie 
Published: March 2021

AbstractThere is evidence from the development and humanitarian sectors that purposeful engagement of women can increase the impact of development. We conducted a literature review to examine whether this is also evident in conservation and natural resource management. The following themes emerged from our review: existing societal and cultural norms affect and generally limit how women can engage in conservation and natural resource management; women interact differently with the environment than men, so if they are excluded, their knowledge and perspectives on particular resources may not be considered in conservation actions; and there is often a lack of resources or dedicated effort by conservation or natural resource management programmes to understand and address the barriers that prevent women's engagement. Although there was evidence of a positive relationship between the engagement of women and environmental outcomes, some studies showed that positive conservation outcomes do not necessarily benefit women, and when women are not considered, conservation activities can perpetuate existing inequities. We conclude that although the importance of integrating gender into conservation is acknowledged in the literature, there is a need to examine how women can be meaningfully engaged in conservation. This must go beyond treating women as a homogenous group, to consider intersectionality including race, ethnicity, age, religion, poverty and disability. In addition, conservation and natural resource management institutions need to address the inclusion of women in their own staff and programmes.
Real-time observation of frequency Bloch oscillations with fibre loop modulation
Authors: Chen Hao , Yang NingNing , Qin Chengzhi , Li Wenwan , Wang Bing , Han Tianwen , Zhang Chi , Liu Weiwei , Wang Kai , Long Hua , Zhang Xinliang , Lu Peixiang 
Published: March 2021

AbstractBloch oscillations (BOs) were initially predicted for electrons in a solid lattice to which a static electric field is applied. The observation of BOs in solids remains challenging due to the collision scattering and barrier tunnelling of electrons. Nevertheless, analogies of electron BOs for photons, acoustic phonons and cold atoms have been experimentally demonstrated in various lattice systems. Recently, BOs in the frequency dimension have been proposed and studied by using an optical micro-resonator, which provides a unique approach to controlling the light frequency. However, the finite resonator lifetime and intrinsic loss hinder the effect from being observed practically. Here, we experimentally demonstrate BOs in a synthetic frequency lattice by employing a fibre-loop circuit with detuned phase modulation. We show that a detuning between the modulation period and the fibre-loop roundtrip time acts as an effective vector potential and hence a constant effective force that can yield BOs in the modulation-induced frequency lattices. With a dispersive Fourier transformation, the pulse spectrum can be mapped into the time dimension, and its transient evolution can be precisely measured. This study offers a promising approach to realising BOs in synthetic dimensions and may find applications in frequency manipulations in optical fibre communication systems.
Tumour cells express functional lymphatic endothelium-specific hyaluronan receptor in vitro and in vivo: Lymphatic mimicry promotes oral oncogenesis?
Authors: Karinen Sini , Juurikka Krista , Hujanen Roosa , Wahbi Wafa , Hadler-Olsen Elin , Svineng Gunbjørg , Eklund Kari K. , Salo Tuula , Åström Pirjo , Salem Abdelhakim 
Published: March 2021

AbstractLymphatic metastasis represents the main route of tumour cell dissemination in oral squamous cell carcinoma (OSCC). Yet, there are no FDA-approved therapeutics targeting cancer-related lymphangiogenesis to date. The lymphatic vessel endothelial hyaluronic acid receptor 1 (LYVE-1), a specific lymphatic marker, is associated with poor survival in OSCC patients. In this study, we present a potential novel mechanism of lymphatic metastasis in OSCC—lymphatic mimicry (LM), a process whereby tumour cells form cytokeratin+/LYVE-1+, but podoplanin-negative, mosaic endothelial-like vessels. LM was detected in one-third (20/57; 35.08%) of randomly selected OSCC patients. The LM-positive patients had shorter overall survival (OS) compared to LM-negative group albeit not statistically significant. Highly-metastatic tumour cells formed distinct LM structures in vitro and in vivo. Importantly, the siRNA-mediated knockdown of LYVE-1 not only impaired tumour cell migration but also blunted their capacity to form LM-vessels in vitro and reduced tumour metastasis in vivo. Together, our findings uncovered, to our knowledge, a previously unknown expression and function of LYVE-1 in OSCC, whereby tumour cells could induce LM formation and promote lymphatic metastasis. Finally, more detailed studies on LM are warranted to better define this phenomenon in the future. These studies could benefit the development of targeted therapeutics for blocking tumour-related lymphangiogenesis.
Asymmetry underlies stability in power grids
Authors: Molnar Ferenc , Nishikawa Takashi , Motter Adilson E. 
Published: March 2021

AbstractBehavioral homogeneity is often critical for the functioning of network systems of interacting entities. In power grids, whose stable operation requires generator frequencies to be synchronized—and thus homogeneous—across the network, previous work suggests that the stability of synchronous states can be improved by making the generators homogeneous. Here, we show that a substantial additional improvement is possible by instead making the generators suitably heterogeneous. We develop a general method for attributing this counterintuitive effect to converse symmetry breaking, a recently established phenomenon in which the system must be asymmetric to maintain a stable symmetric state. These findings constitute the first demonstration of converse symmetry breaking in real-world systems, and our method promises to enable identification of this phenomenon in other networks whose functions rely on behavioral homogeneity.
Detection of copy number variation associated with ventriculomegaly in fetuses using single nucleotide polymorphism arrays
Authors: Xue Huili , Yu Aili , Lin Na , Chen Xuemei , Lin Min , Wang Yan , Huang Hailong , Xu Liangpu 
Published: March 2021

AbstractEtiopathogenesis of fetal ventriculomegaly is poorly understood. Associations between fetal isolated ventriculomegaly and copy number variations (CNVs) have been previously described. We investigated the correlations between fetal ventriculomegaly—with or without other ultrasound anomalies—and chromosome abnormalities. 222 fetuses were divided into four groups: (I) 103 (46.4%) cases with isolated ventriculomegaly, (II) 41 (18.5%) cases accompanied by soft markers, (III) 33 (14.9%) cases complicated with central nervous system (CNS) anomalies, and (IV) 45 (20.3%) cases with accompanying anomalies. Karyotyping and single nucleotide polymorphism (SNP) array were used in parallel. Karyotype abnormalities were identified in 15/222 (6.8%) cases. Karyotype abnormalities in group I, II, III, and IV were 4/103 (3.9%), 2/41 (4.9%), 4/33 (12.1%), and 5/45 (11.1%), respectively. Concerning the SNP array analysis results, 31/222 (14.0%) were CNVs, CNVs in groups I, II, III, and IV were 11/103 (10.7%), 6/41 (14.6%), 9/33 (27.3%), and 5/45 fetuses (11.1%), respectively. Detections of clinical significant CNVs were higher in non-isolated ventriculomegaly than in isolated ventriculomegaly (16.81% vs 10.7%, P = 0.19). SNP arrays can effectively identify CNVs in fetuses with ventriculomegaly and increase the abnormal chromosomal detection rate by approximately 7.2%, especially ventriculomegaly accompanied by CNS anomalies.