bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation framework for systems models
Authors: Braakman Sietse , Pathmanathan Pras , Moore Helen
Published: December 2021

As decisions in drug development increasingly rely on predictions from mechanistic systems models, assessing the predictive capability of such models is becoming more important. Several frameworks for the development of quantitative systems pharmacology (QSP) models have been proposed. In this paper, we add to this body of work with a framework that focuses on the appropriate use of qualitative and quantitative model evaluation methods. We provide details and references for those wishing to apply these methods, which include sensitivity and identifiability analyses, as well as concepts such as validation and uncertainty quantification. Many of these methods have been used successfully in other fields, but are not as common in QSP modeling. We illustrate how to apply these methods to evaluate QSP models, and propose methods to use in two case studies. We also share examples of misleading results when inappropriate analyses are used.
Multi‐user geometry and geography augmented reality applications for collaborative and gamified STEM learning in primary school
Authors: Yegorina Darya , Armstrong Inna , Kravtsov Alexey , Merges Kevin , Danhoff Christine
Published: December 2021

Augmented reality (AR) technology has been gaining a meaningful position in the education sector with multiple subjects’ application to support teaching and learning experiences. Thanks to the advancement of hardware and technological platforms it is becoming easier to adopt AR technology at schools. This study represents a systematic literature review of AR application in the area of science, technology, engineering and mathematics (STEM) education at primary school level with the focus on collaborative and gamified practices applied to mobile application for geometry and geography subjects. The main objective of this paper is to investigate and analyse the main characteristics and state of the art of the AR STEM gamified collaborative applications for geometry and geography in primary education and their efficiency on the teaching and learning process. This study performs qualitative analysis of the content of 97 articles that provide an overview of the relevant mobile applications for this systematic literature review, book chapters and conference articles published from 2010 to 2021. The main contribution of this article is in the area of in‐app augmented collaborative experiences in geometry and geography learning in primary grades for further research and technology development. In addition, an extensive analysis of the existing AR mobile applications from peer reviewed articles for the above‐mentioned subjects is provided in a comparative table.
What is the satisfiability threshold of random balanced Boolean expressions?
Authors: Lindenstrauss Naomi , Talagrand Michel
Published: December 2021

We consider the model of random Boolean expressions based on balanced binary trees with leaves, to which are randomly attributed one of Boolean variables or their negations. We prove that if for every it holds that then asymptotically with high probability the Boolean expression is either a tautology or an antitautology. Our methods are based on the study of a certain binary operation on the set of probability measures on for a finite set I.
Childhood maltreatment experiences and emotion perception in young Chinese adults: Sex as a moderator
Authors: Zhao Yiran , Wu Chao
Published: December 2021

Men and women seem to perceive and react differently to emotional stimuli and have different susceptibilities to childhood trauma. With a cross‐sectional design, this study aimed to investigate whether specific patterns of childhood‐maltreatment experiences are associated with specific patterns of emotion perception and the sex differences in this relationship. A total of 173 adults rated valence, arousal, and dominance for 60 pictures (varying in pleasantness, unpleasantness, and neutral emotion) from the International Affective Picture System and completed the Childhood Trauma Questionnaire‐Short Form. Using a partial least squares (PLS) regression analysis, after controlling for depressive and anxious states, recent stressful life events, personality, and cognitive reappraisal strategy, we identified a profile (linear combination) of childhood‐maltreatment experiences (emotional neglect, physical neglect, and physical abuse) that was associated with a profile of emotion‐perception dimensions (perceiving negative visual stimuli as more unpleasant and subservient, positive stimuli as more pleasant and dominant, and neutral stimuli as more arousing). This association pattern was significant only for the male participants. Hence, our findings suggest that childhood maltreatment might make men more “emotional” in their adulthood. The impact of this childhood‐maltreatment‐associated alteration in emotion perception on male mental health needs further investigation.
In Situ Electrochemical Transformation toward Structure Optimized VEG@MXene Cathode for Enhanced Zinc‐Ion Storage
Authors: Li Xinjie , Zhu Xiaodong , Cao Ziyi , Xu Zhenglong , Shen Jianfeng , Ye Mingxin
Published: December 2021

Vanadium‐based derivatives, featuring affordable cost and high theoretical capacity, have gathered widespread interest in the context of aqueous zinc‐ion batteries (ZIBs). However, the further application of vanadium‐based materials is hindered by the limited electrical conductivity and cycling lifespan. Herein, 1D chain‐like structure vanadyl ethylene glycolate (VEG, (VO(CH2O)2)), growing on the Ti3C2Tx MXene nanosheets, is synthesized via a one‐step oil‐bath heating process as cathode materials for ZIBs. Benefiting from the hybrid structure with high conductivity and abundant reactive sites, the VEG@MXene cathode exhibits a remarkable specific capacity (360.3 mAh g−1 at 0.5 A g−1), and impressive capacity retention (up to 85.2% after 3000 cycles at 10 A g−1). Mechanism analysis reveals a gradual phase transition from the original VEG on MXene to the stable Zn3V2O7(OH)2·2H2O nanoflakes accompanied by continuous zinc ion intercalation/deintercalation, offering more pathways for zinc ion transport. This work suggests that engineering conductivity‐enhanced vanadium‐based materials is a rational approach for developing promising cathode materials of ZIBs.
Using Metal Cation to Control the Microstructure of Cobalt Oxide in Energy Conversion and Storage Applications
Authors: Zhang Hao , Geng Songyuan , Ouyang Mengzheng , Mao Mingxuan , Xie Fang , Riley D. Jason
Published: December 2021

Herein, a facile and efficient synthesis of microstructured Co3O4 for both supercapacitor and water‐splitting applications is reported. Metal cations (Fe3+, Cu2+) serve as structure‐directing agents regulating the structure of Co compounds, which are subsequently annealed to yield Co3O4. Detailed characterizations and density functional theory (DFT) calculations reveal that the in situ Cl‐doping introduces oxygen defects and provides abundant electroactive sites, and narrows the bandgap, which enhances the electron excitation of the as‐formed Co3O4. The as‐prepared Cl‐doped Co3O4 hierarchical nanospheres (Cl‐Co3O4‐h) display a high specific capacitance of 1629 F g−1 at 1 A g−1 as an electrode for supercapacitors, with excellent rate capability and cyclability. The Cl‐Co3O4‐h//activated carbon (AC) asymmetric supercapacitor (ASC) electrode achieves a specific capacitance of 237 F g−1 at 1 A g−1, with an energy density of 74 Wh kg−1 at a power density of 807 W kg−1 and even maintains 47 Wh kg−1 at the higher‐power density of 24.2 kW kg−1. An integrated electrolyzer for water‐splitting with Cl‐Co3O4‐h as both cathode and anode can be driven by Cl‐Co3O4‐h//AC ASC. The electrolyzer provides a high current density of 35 mA cm–2 at a cell voltage of 1.6 V, with good current density retention over 50 h.
Self‐Organized Spatiotemporal Mineralization of Hydrogel: A Simulant of Osteon
Authors: Wu Mingzhen , Zhao Yao , Jiang Haolun , Xu Xiaoyang , Wang Dingqian , Xu Xinyuan , Zhou Yahong , Tan Hong , Ding Chunmei , Li Jianshu
Published: December 2021

Nature creates fascinating self‐organized spatiotemporal patterns through the delicate control of reaction‐diffusion dynamics. As the primary unit of cortical bone, osteon has concentric lamellar architecture, which plays a crucial role in the mechanical and physiological functions of bone. However, it remains a great challenge to fabricate the osteon‐like structure in a natural self‐organization way. Taking advantage of the nonequilibrium reaction in hydrogels, a simple mineralization strategy to closely mimic the formation of osteon in a mild physiological condition is developed. By constructing two reverse concentration gradients of ions from periphery to interior of cylindrical hydrogel, spatiotemporal self‐organization of calcium phosphate in concentric rings is generated. It is noteworthy that minerals in different layers possess diverse contents and crystalline phases, which further guide the adhesion and spread of osteoblasts on these patterns, resembling the architecture and cytological behavior of osteon. Besides, theoretical data indicates the predominate role of ion concentrations and pH values of solution, in good accordance with experimental results. Independent of precise instruments, this lifelike method is easily obtained, cost‐efficient, and effectively imitates the mineral deposition in osteon from a physiochemical view. The strategy may be expanded to develop other functional material patterns via spatiotemporal self‐organization.
Biodegradable, Breathable Leaf Vein‐Based Tactile Sensors with Tunable Sensitivity and Sensing Range
Authors: Liu Yue , Tao Juan , Yang Wenkai , Zhang Yufei , Li Jing , Xie Huilin , Bao Rongrong , Gao Wenchao , Pan Caofeng
Published: December 2021

Resistive pressure sensors have been widely studied for application in flexible wearable devices due to their outstanding pressure‐sensitive characteristics. In addition to the outstanding electrical performance, environmental friendliness, breathability, and wearable comfortability also deserve more attention. Here, a biodegradable, breathable multilayer pressure sensor based piezoresistive effect is presented. This pressure sensor is designed with all biodegradable materials, which show excellent biodegradability and breathability with a three‐dimensional porous hierarchical structure. Moreover, due to the multilayer structure, the contact area of the pressure sensitive layers is greatly increased and the loading pressure can be distributed to each layer, so the pressure sensor shows excellent pressure‐sensitive characteristics over a wide pressure sensing range (0.03–11.60 kPa) with a high sensitivity (6.33 kPa−1). Furthermore, the sensor is used as a human health monitoring equipment to monitor the human physiological signals and main joint movements, as well as be developed to detect different levels of pressure and further integrated into arrays for pressure imaging and a flexible musical keyboard. Considering the simple manufacturing process, the low cost, and the excellent performance, leaf vein‐based pressure sensors provide a good concept for environmentally friendly wearable devices.
Limiting sensitive values in an anonymized table while reducing information loss via p‐proportion
Authors: Dosselmann Richard , Hamilton Howard J.
Published: December 2021

The ‐proportion model bounds the proportion of sensitive values of a sensitive attribute in each equivalence class of an anonymized database table in order to limit the ability of a user to link an individual or entity to a sensitive value in that table. Nonsensitive values are not subject to any such constraints, which reduces the amount of anonymization needed to meet the requirements of this model. This leads to less information loss in an anonymized table. Anonymization is performed using an extension of the Mondrian algorithm that incorporates categorical attributes. Known as the adapted Mondrian algorithm, it generalizes a value of a categorical attribute to a set. Existing algorithms, by comparison, replace one value of a predefined hierarchy by another. The ‐proportion model is compared against the ()‐anonymity model using both the progressive local recoding and (adapted) Mondrian algorithms. Experiments demonstrate the advantage of ‐proportion and Mondrian over ()‐anonymity and progressive local recoding in terms of reduced information loss, measured using the normalized certainty penalty, discernibility metric, and classification metric.
MiR‐125b enhances doxorubicin‐induced cardiotoxicity by suppressing the nucleus‐cytoplasmic translocation of YAP via targeting STARD13
Authors: Jin Xiaoping , Yu Wande , Ye Peng
Published: December 2021

The clinical application of doxorubicin (Dox) is limited due to its cardiotoxicity, while the pathogenesis remains to be fully understood. Recent studies have suggested that microRNA (miRNA) plays an important role in Dox‐induced cardiotoxicity. This work aims to investigate the effects of miR‐125b in Dox‐induced cardiotoxicity. Here, mice model combined with cell line analysis were used, and cell viability assay, detection of reactive oxygen species (ROS), malondialdehyde (MDA) activity, lactate dehydrogenase (LDH) activity, glutathione (GSH) level, glutathione peroxidase (GSH‐Px) level, superoxide dismutase (SOD) activity, and histopathological changes were performed to characterize miR‐125b effects; real‐time quantitative polymerase chain reaction (PCR), luciferase reporter assay, RNA immunoprecipitation, and western blot analysis were subjected to reveal the underlying mechanisms. It was found that miR‐125b level was upregulated in myocardial cell line H9C2 treated with Dox and miR‐125b overexpression enhanced Dox‐induced cytotoxicology of H9C2 cells, while miR‐125b inhibition exhibited a protective effect by measuring ROS level and cell viability. In consistent, in vivo experiments with miR‐125b agomir or antagomir obtained a consistent result through examining the activity of MDA, LDH, GSH, GSH‐Px, SOD, and histopathological changes. Furthermore, we found that miR‐125b could target STARD13 and thus suppressed the nucleus‐cytoplasmic translocation of yes‐associated protein (YAP). Additionally, this STARD13/YAP axis is necessary for miR‐125b‐mediated regulation on Dox‐induced cytotoxicology of H9C2 cells. In conclusion, our study demonstrated that miR‐125b could enhance Dox‐induced cardiotoxicity through targeting the STARD13/YAP axis.
Search for sub-eV axion-like resonance states via stimulated quasi-parallel laser collisions with the parameterization including fully asymmetric collisional geometry
Authors:   The SAPPHIRES collaboration, Homma Kensuke , Kirita Yuri , Hashida Masaki , Hirahara Yusuke , Inoue Shunsuke , Ishibashi Fumiya , Nakamiya Yoshihide , Neagu Liviu , Nobuhiro Akihide , Ozaki Takaya , Rosu Madalin-Mihai , Sakabe Shuji , Tesileanu Ovidiu
Published: December 2021

Abstract

We have searched for axion-like resonance states by colliding optical photons in a focused laser field (creation beam) by adding another laser field (inducing beam) for stimulation of the resonance decays, where frequency-converted signal photons can be created as a result of stimulated photon-photon scattering via exchanges of axion-like resonances. A quasi-parallel collision system (QPS) in such a focused field allows access to the sub-eV mass range of resonance particles. In past searches in QPS, for simplicity, we interpreted the scattering rate based on an analytically calculable symmetric collision geometry in both incident angles and incident energies by partially implementing the asymmetric nature to meet the actual experimental conditions. In this paper, we present new search results based on a complete parameterization including fully asymmetric collisional geometries. In particular, we combined a linearly polarized creation laser and a circularly polarized inducing laser to match the new parameterization. A 0.10 mJ/31 fs Ti:sapphire laser pulse and a 0.20 mJ/9 ns Nd:YAG laser pulse were spatiotemporally synchronized by sharing a common optical axis and focused into the vacuum system. Under a condition in which atomic background processes were completely negligible, no significant scattering signal was observed at the vacuum pressure of 2.6 × 10−5 Pa, thereby providing upper bounds on the coupling-mass relation by assuming exchanges of scalar and pseudoscalar fields at a 95% confidence level in the sub-eV mass range.
de Sitter vacua from ten dimensions
Authors: Kachru Shamit , Kim Manki , McAllister Liam , Zimet Max
Published: December 2021

Abstract

We analyze the de Sitter construction of [1] using ten-dimensional supergravity, finding exact agreement with the four-dimensional effective theory. Starting from the fermionic couplings in the D7-brane action, we derive the ten-dimensional stress-energy due to gaugino condensation on D7-branes. We demonstrate that upon including this stress-energy, as well as that due to anti-D3-branes, the ten-dimensional equations of motion require the four-dimensional curvature to take precisely the value determined by the four-dimensional effective theory of [1].
Non-local reparametrization action in coupled Sachdev-Ye-Kitaev models
Authors: Milekhin Alexey
Published: December 2021

Abstract

We continue the investigation of coupled Sachdev-Ye-Kitaev (SYK) models without Schwarzian action dominance. Like the original SYK, at large N and low energies these models have an approximate reparametrization symmetry. However, the dominant action for reparametrizations is non-local due to the presence of irrelevant local operator with small conformal dimension. We semi-analytically study different thermodynamic properties and the 4-point function and demonstrate that they significantly differ from the Schwarzian prediction. However, the residual entropy and maximal chaos exponent are the same as in Majorana SYK. We also discuss chain models and finite N corrections.
Maximally supersymmetric RG flows in 4D and integrability
Authors: Caetano João , Peelaers Wolfger , Rastelli Leonardo
Published: December 2021

Abstract

We revisit the leading irrelevant deformation of $$ \mathcal{N} $$
N
= 4 Super Yang-Mills theory that preserves sixteen supercharges. We consider the deformed theory on S3× ℝ. We are able to write a closed form expression of the classical action thanks to a formalism that realizes eight supercharges off shell. We then investigate integrability of the spectral problem, by studying the spin-chain Hamiltonian in planar perturbation theory. While there are some structural indications that a suitably defined deformation might preserve integrability, we are unable to settle this question by our two-loop calculation; indeed up to this order we recover the integrable Hamiltonian of undeformed $$ \mathcal{N} $$
N
= 4 SYM due to accidental symmetry enhancement. We also comment on the holographic interpretation of the theory.
Semi-classical analysis of the string theory cigar
Authors: Jafferis Daniel Louis , Schneider Elliot
Published: December 2021

Abstract

We study the semi-classical limit of the reflection coefficient for the SL(2, ℝ)k/U(1) CFT. For large k, the CFT describes a string in a Euclidean black hole of 2-dimensional dilaton-gravity, whose target space is a cigar with an asymptotically linear dilaton. This sigma-model description is weakly coupled in the large k limit, and we investigate the saddle-point expansion of the functional integral that computes the reflection coefficient. As in the semi-classical limit of Liouville CFT studied in [1], we find that one must complexify the functional integral and sum over complex saddles to reproduce the limit of the exact reflection coefficient. Unlike Liouville, the SL(2, ℝ)k/U(1) CFT admits bound states that manifest as poles of the reflection coefficient. To reproduce them in the semi-classical limit, we find that one must sum over configurations that hit the black hole singularity, but nevertheless contribute to the saddle-point expansion with finite action.
Bulk entropy is crucial to validate the second law of the extended black hole thermodynamics
Authors: Dai De-Chang , Minic Djordje , Stojkovic Dejan
Published: December 2021

Abstract

The extended black hole thermodynamics in which the cosmological constant plays the role of pressure significantly enriches the phase structure of the theory. In order to understand the extended black hole thermodynamics more precisely, we let the value of the cosmological constant vary dynamically via tunneling from one vacuum to another in a black hole induced vacuum decay. In this process, entropy of the matter/energy released by a black hole is crucial to validate the second law of thermodynamics. In other words, without taking this bulk entropy into account, entropy associated with the black hole and cosmological horizons may not always increase. Since the bulk entropy is not represented by the black hole and the cosmological horizons, this result calls for a more careful interpretation of the holographic principle in which environmental effects are taken into account.
TM4SF5-mediated liver malignancy involves NK cell exhaustion-like phenotypes
Authors: Sun Hyunseung , Kim Eunmi , Ryu Jihye , Lee Hyejin , Shin Eun-Ae , Lee Minhyeong , Lee Haesong , Lee Jeong-Hoon , Yoon Jung-Hwan , Song Dae-Geun , Kim Semi , Lee Jung Weon
Published: December 2021

Aberrant extracellular matrix and immune cell alterations within the tumor microenvironment promote the pathological progression of liver carcinogenesis. Although transmembrane 4 L six family member 5 (TM4SF5) is involved in liver fibrosis and cancer, its mechanism avoiding immune surveillance during carcinogenesis remains unknown. We investigated how TM4SF5-mediated signaling caused immune evasion using in vitro primary cells and in vivo liver tissues from genetic or chemically induced mouse models. TM4SF5-transgenic and diethylnitrosamine (DEN)-induced liver cancer mouse models exhibited fibrotic and cancerous livers, respectively, with enhanced TM4SF5, pY705STAT3, collagen I, and laminin γ2 levels. These TM4SF5-mediated effects were abolished by TM4SF5 inhibitor, 4′-(p-toluenesulfonylamido)-4-hydroxychalcone (TSAHC). TM4SF5-dependent tumorigenesis involved natural killer (NK) cell exhaustion-like phenotypes including the reduction of NK cell number or function, which were blocked with TSAHC treatment. TM4SF5 expression in cancer cells downregulated stimulatory ligands and receptors for NK cell cytotoxicity, including SLAMF6, SLAMF7, MICA/B, and others. TM4SF5 suppression or inhibition reduced STAT3 signaling activity and recovered the receptor levels and NK cell surveillance, leading to reduced fibrotic and cancerous phenotypes, and longer survival. Altogether, these findings suggest that TM4SF5-mediated STAT3 activity for extracellular matrix modulation is involved in the progression of liver disease to HCC and that TM4SF5 appears to suppress NK cells during liver carcinogenesis.
Patterns of resemblance and Bachmann-Howard fixed points
Authors: Freund Anton
Published: December 2021

Timothy Carlson’s patterns of resemblance employ the notion of $$\Sigma _1$$

Σ
1

-elementarity to describe large computable ordinals. It has been conjectured that a relativization of these patterns to dilators leads to an equivalence with $$\Pi ^1_1$$

Π
1
1

-comprehension (Question 27 of A. Montalbán’s “Open questions in reverse mathematics”, Bull. Symb. Log. 17(3)2011, 431-454). In the present paper we prove this conjecture. The crucial direction of the equivalence (towards $$\Pi ^1_1$$

Π
1
1

-comprehension) is reduced to a previous result of the author, which is concerned with relativizations of the Bachmann-Howard ordinal.
Rank and border rank of Kronecker powers of tensors and Strassen's laser method
Authors: Conner Austin , Gesmundo Fulvio , Landsberg Joseph M. , Ventura Emanuele
Published: December 2021

We prove that the border rank of the Kronecker square of the little Coppersmith–Winograd tensor $$T_{cw,q}$$

T

c
w
,
q

is the square of its border rank for $$q > 2$$

q
>
2

and that the border rank of its Kronecker cube is the cube of its border rank for $$q > 4$$

q
>
4

. This answers questions raised implicitly by Coppersmith & Winograd (1990, §11)
and explicitly by Bläser (2013, Problem 9.8) and rules out the possibility of proving new upper bounds on the exponent of matrix multiplication using the square or cube of a little Coppersmith–Winograd tensor in this range.

In the positive direction, we enlarge the list of explicit tensors potentially useful for Strassen's laser method, introducing a skew-symmetric version of the Coppersmith–Winograd tensor, $$T_{skewcw,q}$$

T

s
k
e
w
c
w
,
q

. For $$q = 2$$

q
=
2

, the Kronecker square of this tensor coincides with the $$3\times 3$$

3
×
3

determinant polynomial, $$\det_{3} \in \mathbb{C}^{9} \otimes \mathbb{C}^{9} \otimes \mathbb{C}^{9}$$

det
3

∈

C

9

⊗

C

9

⊗

C

9

, regarded as a tensor. We show that this tensor could potentially be used to show that the exponent of matrix multiplication is two.

We determine new upper bounds for the (Waring) rank and the (Waring) border rank of $$\det_3$$

det
3

, exhibiting a strict submultiplicative behaviour for $$T_{skewcw,2}$$

T

s
k
e
w
c
w
,
2

which is promising for the laser method.

We establish general results regarding border ranks of Kronecker powers of tensors, and make a detailed study of Kronecker squares of tensors in $$\mathbb{C}^{3} \otimes \mathbb{C}^{3} \otimes \mathbb{C}^{3}$$

C

3

⊗

C

3

⊗

C

3

.
MRI follow-up for pancreatic intraductal papillary mucinous neoplasm: an ultrashort versus long protocol
Authors: Johansson Katarina , Mustonen Harri , Nieminen Heini , Haglund Caj , Lehtimäki Tiina E. , Seppänen Hanna
Published: December 2021

Purpose

To evaluate whether an ultrashort-protocol (USP) MRI including only T2-weighted HASTE axial and 3D MRCP SPACE sequences adequately measures the largest diameter of the largest cyst and the main pancreatic duct (MPD) and identifies worrisome features (WF) and high-risk stigmata (HRS) when compared to longer protocols (LP, long protocol; SP, short protocol; S-LP, short or long protocol). We also calculated reductions in costs associated with USP.

Methods

This retrospective study included 183 IPMN patients. Two radiologists compared two imaging sets (USP versus S-LP) per patient, comparing the mean values of the largest cyst and MPD and agreement regarding the presence or absence of cystic or MPD mural nodules and solid pancreatic tumors. The interobserver agreement for cystic mural nodules and WF/HRS was evaluated, using the Bland-Altman plot and Cohen’s Kappa.

Results

A total of 112 IPMN patients were evaluated. For detecting cysts or MPD nodules, WF/HRS, and solid pancreatic tumors, USP and S-LP coincided in 94.9%, 99.1%, 92.4%, and 99.1% of cases, respectively. Both USP and S-LP identified all true cystic mural nodules. The mean size of the largest cyst and MPD was 19.48/19.67 mm and 3.24/3.33 mm using USP versus S-LP, while the mean differences for USP versus S-LP were 0.19 mm and 0.08 mm. The USP cost was 39% of LP cost and 77% of SP. Interobserver agreement was moderate to strong.

Conclusions

For IPMN surveillance, an ultrashort-protocol MRI provides nearly identical information to the more expensive longer protocols.

Graphical abstract
Zusammenarbeit mit klinischen Auftragsforschungsinstituten
Authors: Adorf Adeline , Lorenz Katrin , Feltgen Nicolas , Wilhelm Barbara ,   die AG DOG Klinische Studienzentren, Peters Tobias , Pielen Amelie , Böhringer Daniel , Seger Dorina , Wozar Fabian , Otto Stefanie , Petermann Kerstin , Molnar Fanni , Holz Frank , Schüttauf Frank , Laure Ieva , Beck Anna , Fornoff Luise , Dona Frau , Hinzelmann Lisa , Liegl Raffael , Dulz Simon , Grohmann Carsten , Winterhalder Stephanie , Allgeier Katharina , Subottin Dimitrij , Mangold Anna , Choritz Lars , Kreis Stefan , Eter Nicole , Kellner Ulrich , Lang Monica , Gamulescu Andreea , Tamm Svenja , Ziemssen Focke , Kallus Katarzyna , Aisenbrey Sabine , Seitz Immanuel , Lengnink Tanja , Kahle Nadine , Bajor Anna , von Livonius Bettina , Rehak Matus , Guthoff Rainer , Hofmann Martina , Ehlken Christoph , Koschinski Andrea , Spital Georg , Schargus Marc , Khoramnia Ramin , Enders Philip , Altay Lebriz , Prinz Beate
Published: December 2021

Klinische Studien mit Arzneimitteln oder Medizinprodukten stellen zunehmend komplexe Anforderungen an Sponsoren und beteiligte Zentren. In den letzten 2 Jahrzehnten delegieren Sponsoren regulatorische sowie organisatorische Studienaufgaben zunehmend an medizinische Auftragsinstitute (engl. Clinical Research Organisation [CRO]). In der Regel sind diese Unternehmen die Hauptschnittstelle für die Zusammenarbeit mit den beteiligten Studienzentren. Hauptzweck der Mitwirkung ist die Unterstützung der Studienzentren zur Erzielung einer maximalen Studienqualität. Die in der Arbeitsgemeinschaft DOG Klinische Studienzentren verbundenen Studienzentren beobachten unterschiedliche Erfahrungen in der Zusammenarbeit mit CROs. Solche Erfahrungen sollen künftig systematisch an den beteiligten Zentren erfasst und vom Leiter der klinischen Studie ausgewertet werden. Die Spiegelung dieser Erfahrungen an die jeweiligen Auftragsinstitute und die sie beauftragenden Sponsoren kann in der Zukunft zur Qualität der Unterstützung durch CROs und damit zur Studienqualität beitragen. Die vorliegende Arbeit stellt vor, welche Bereiche der Zusammenarbeit im Fragebogen erfasst und analysiert werden.
Dynamic changes in the association between maternal mRNAs and endoplasmic reticulum during ascidian early embryogenesis
Authors: Goto Toshiyuki , Torii Shuhei , Kondo Aoi , Kawakami Junji , Yagi Haruka , Suekane Masato , Kataoka Yosky , Nishikata Takahito
Published: December 2021

Axis formation is one of the most important events occurring at the beginning of animal development. In the ascidian egg, the antero-posterior axis is established at this time owing to a dynamic cytoplasmic movement called cytoplasmic and cortical reorganisation. During this movement, mitochondria, endoplasmic reticulum (ER), and maternal mRNAs (postplasmic/PEM RNAs) are translocated to the future posterior side. Although accumulating evidence indicates the crucial roles played by the asymmetrical localisation of these organelles and the translational regulation of postplasmic/PEM RNAs, the organisation of ER has not been described in sufficient detail to date owing to technical difficulties. In this study, we developed three different multiple staining protocols for visualising the ER in combination with mitochondria, microtubules, or mRNAs in whole-mount specimens. We defined the internally expanded “dense ER” using these protocols and described cisterna-like structures of the dense ER using focused ion beam-scanning electron microscopy. Most importantly, we described the dynamic changes in the colocalisation of postplasmic/PEM mRNAs and dense ER; for example, macho-1 mRNA was detached and excluded from the dense ER during the second phase of ooplasmic movements. These detailed descriptions of the association between maternal mRNA and ER can provide clues for understanding the translational regulation mechanisms underlying axis determination during ascidian early embryogenesis.
Closure of German Hard Coal Mines: Effects and Legal Aspects of Mine Flooding
Authors: Stemke Marion , Wieber Georg
Published: December 2021

Following the closure of the last hard coal mines in Germany, pumping is no longer necessary. However, the resulting rise of mine water can affect the environment. Laws have been enacted at the European and national level to protect properties. Within the framework of the approval procedure, it must be determined whether the cessation of pumping may cause unacceptable effects, including water pollution. With regard to water protection, the European Union has issued the Water Framework and Groundwater Directives, which have been implemented into German national law. These contain the prohibition of deterioration and the requirement for improvement, with the aim of maintaining or achieving good ecological and chemical status. However, before the target mine water level is reached, the water does not need to comply, since although the pumps are switched off, no mine water is being discharged. This also rules out permit requirements, which only go into effect when the target mine water level has been reached and mine water is discharging. Obviously, however, detailed planning before then is necessary.
Models: the fourth dimension of computer science
Authors: Thalheim Bernhard
Published: December 2021

Models are a universal instrument in science, technology, and daily life. They function as instruments in almost every scenario. Any human activity can be (and is) supported by models, e.g. reason, explain, design, act, predict, explore, communicate, collaborate, interact, orient, direct, guide, socialises, perceive, reflect, develop, making sense, teach, learn, imagine, etc. This universal suitability is also the basis for a wide use of models and modelling in Computer Science and Engineering. We claim that models form the fourth dimension in Computer Science. This paper sketches and systematises the main ingredients of the study model and modelling.
Defining the landscape of metabolic dysregulations in cancer metastasis
Authors: Abdul Kader Sara , Dib Shaima , Achkar Iman W. , Thareja Gaurav , Suhre Karsten , Rafii Arash , Halama Anna
Published: December 2021

Metastasis is the primary cause of cancer related deaths due to the limited number of efficient druggable targets. Signatures of dysregulated cancer metabolism could serve as a roadmap for the determination of new treatment strategies. However, the metabolic signatures of metastatic cells remain vastly elusive. Our aim was to determine metabolic dysregulations associated with high metastatic potential in breast cancer cell lines. We have selected 5 triple negative breast cancer (TNBC) cell lines including three with high metastatic potential (HMP) (MDA-MB-231, MDA-MB-436, MDA-MB-468) and two with low metastatic potential (LMP) (BT549, HCC1143). The normal epithelial breast cell line (hTERT-HME1) was also investigated. The untargeted metabolic profiling of cells and growth media was conducted and total of 479 metabolites were quantified. First we characterized metabolic features differentiating TNBC cell lines from normal cells as well as identified cell line specific metabolic fingerprints. Next, we determined 92 metabolites in cells and 22 in growth medium that display significant differences between LMP and HMP. The HMP cell lines had elevated level of molecules involved in glycolysis, TCA cycle and lipid metabolism. We identified metabolic advantages of cell lines with HMP beyond enhanced glycolysis by pinpointing the role of branched chain amino acids (BCAA) catabolism as well as molecules supporting coagulation and platelet activation as important contributors to the metastatic cascade. The landscape of metabolic dysregulations, characterized in our study, could serve as a roadmap for the identification of treatment strategies targeting cancer cells with enhanced metastatic potential.
Statistical study of thermoradiative and photovoltaic cells based on a two-level model
Authors: Fernández J. J.
Published: December 2021

We use a two-level energy model to understand the conversion process that takes place in thermoradiative cells and to compare it with the conversion process that happens in photovoltaic cells. In this way, we show that in both kinds of converters the conversion process can be studied as the succession of a change in the populations of the levels that occur at constant chemical potential and a change in the value of the chemical potential of the two levels that happens while keeping their populations constant. As an application of the model, we will discuss why in thermoradiative cells the open-circuit voltage is negative while it is positive in photovoltaic cells. We also show that the expression for the open-circuit voltage is the same in both kinds of cells but that due to the values of the temperatures it is negative in thermoradiative cells and positive in photovoltaic ones.
Can activated titanium interbody cages accelerate or enhance spinal fusion? a review of the literature and a design for clinical trials
Authors: Toop Nathaniel , Gifford Connor , Motiei-Langroudi Rouzbeh , Farzadi Arghavan , Boulter Daniel , Forghani Reza , Farhadi H. Francis
Published: December 2021

While spinal interbody cage options have proliferated in the past decade, relatively little work has been done to explore the comparative potential of biomaterial technologies in promoting stable fusion. Innovations such as micro-etching and nano-architectural designs have shown purported benefits in in vitro studies, but lack clinical data describing their optimal implementation. Here, we critically assess the pre-clinical data supportive of various commercially available interbody cage biomaterial, topographical, and structural designs. We describe in detail the osteointegrative and osteoconductive benefits conferred by these modifications with a focus on polyetheretherketone (PEEK) and titanium (Ti) interbody implants. Further, we describe the rationale and design for two randomized controlled trials, which aim to address the paucity of clinical data available by comparing interbody fusion outcomes between either PEEK or activated Ti lumbar interbody cages. Utilizing dual-energy computed tomography (DECT), these studies will evaluate the relative implant-bone integration and fusion rates achieved by either micro-etched Ti or standard PEEK interbody devices. Taken together, greater understanding of the relative osseointegration profile at the implant–bone interface of cages with distinct topographies will be crucial in guiding the rational design of further studies and innovations.
Mechanical, Thermal and Microstructural Characteristic of 3D Printed Polylactide Composites with Natural Fibers: Wood, Bamboo and Cork
Authors: Mazur Karolina E. , Borucka Aleksandra , Kaczor Paulina , Gądek Szymon , Bogucki Rafał , Mirzewiński Dariusz , Kuciel Stanisław
Published: December 2021

In the study, polylactide-based (PLA) composites modified with natural particles (wood, bamboo, and cork) and with different levels of infilling (100%, 80%, and 60%) obtained by fused deposition modeling were tested. The effect of fiber type, infill level and crystallization rate on the mechanical properties were investigated by using tensile, flexural, and impact tests. The materials were subjected to mechanical tests carried out at 23 and 80 °C. Differential scanning calorimetry were employed to analyze crystallization behavior of composite. Furthermore, hydrothermal degradation was performed, and its effect on the properties was analyzed. The addition of natural fillers and different levels of infilling result in a similar level of reduction in the properties. However, the addition of natural fillers resulted in a slightly lower drop than the lowered infilling rate − 40% and 50% for tensile strength, respectively. Moreover, it was found that, composites made of PLA are more sensitive to high temperatures than to water. The decrease in Young's modulus of PLA at 80 °C was 90%, while after 28 days of hydrodegradation ~ 9%. The addition of fibers reduced this decrease at elevated temperatures. Importantly, in the case of a brittle material such as PLA, the impact strength has been improved by 50% for composites with cork particles and other lignocellulosic composites remained at the same level as for resin. Generally, the thermal treatment of composites increased the degree of crystallinity of the materials, as reflected in the higher results of mechanical tests.
Late Holocene environmental change in Celestun Lagoon, Yucatan, Mexico
Authors: Hardage Kyle , Street Joseph , Herrera-Silveira Jorge A. , Oberle Ferdinand K. J. , Paytan Adina
Published: December 2021

Epikarst estuary response to hydroclimate change remains poorly understood, despite the well-studied link between climate and karst groundwater aquifers. The influence of sea-level rise and coastal geomorphic change on these estuaries obscures climate signals, thus requiring careful development of paleoenvironmental histories to interpret the paleoclimate archives. We used foraminifera assemblages, carbon stable isotope ratios (δ13C) and carbon:nitrogen (C:N) mass ratios of organic matter in sediment cores to infer environmental changes over the past 5300 years in Celestun Lagoon, Yucatan, Mexico. Specimens (> 125 µm) from modern core top sediments revealed three assemblages: (1) a brackish mangrove assemblage of agglutinated Miliammina and Ammotium taxa and hyaline Haynesina (2) an inner-shelf marine assemblage of Bolivina, Hanzawaia, and Rosalina, and (3) a brackish assemblage dominated by Ammonia and Elphidium. Assemblages changed along the lagoon channel in response to changes in salinity and vegetation, i.e. seagrass and mangrove. In addition to these three foraminifera assemblages, lagoon sediments deposited since 5300 cal yr BP are comprised of two more assemblages, defined by Archaias and Laevipeneroplis, which indicate marine Thalassia seagrasses, and Trichohyalus, which indicates restricted inland mangrove ponds. Our data suggest that Celestun Lagoon displayed four phases of development: (1) an inland mangrove pond (5300 BP) (2) a shallow unprotected coastline with marine seagrass and barrier island initiation (4900 BP) (3) a protected brackish lagoon (3000 BP), and (4) a protected lagoon surrounded by mangroves (1700 BP). Stratigraphic (temporal) changes in core assemblages resemble spatial differences in communities across the modern lagoon, from the southern marine sector to the northern brackish region. Similar temporal patterns have been reported from other Yucatan Peninsula lagoons and from cenotes (Nichupte, Aktun Ha), suggesting a regional coastal response to sea level rise and climate change, including geomorphic controls (longshore drift) on lagoon salinity, as observed today. Holocene barrier island development progressively protected the northwest Yucatan Peninsula coastline, reducing mixing between seawater and rain-fed submarine groundwater discharge. Superimposed on this geomorphic signal, assemblage changes that are observed reflect the most severe regional wet and dry climate episodes, which coincide with paleoclimate records from lowland lake archives (Chichancanab, Salpeten). Our results emphasize the need to consider coastal geomorphic evolution when using epikarst estuary and lagoon sediment archives for paleoclimate reconstruction and provide evidence of hydroclimate changes on the Yucatan Peninsula.
Understanding for Which Students and Classes a Socio-Ecological Aggression Prevention Program Works Best: Testing Individual Student and Class Level Moderators
Authors: Bardach Lisa , Yanagida Takuya , Gradinger Petra , Strohmeier Dagmar
Published: December 2021

School-based aggression prevention programs may not be equally effective for all students and classes, depending on student and class characteristics. This study investigated moderators of a cluster randomized controlled socio-ecological aggression prevention program’s effectiveness (change from pretest to posttest, sample: 2,042 preadolescents, mean age = 11.7 years, SD = 0.09, 47.6% girls) and sustainability (change from posttest to follow-up test, sample: 659 preadolescents, mean age = 12.7 years, SD = 0.08, 47.9% girls). The program worked better in multicultural classes, as greater ethnic diversity strengthened the program’s effectiveness and sustainability. Moderating effects of a positive social class climate and higher baseline levels of aggressive behavior and victimization were also found. These results advance socio-ecological theorizing and can help develop more contextualized interventions.
Fireside Corrosion of Heat Exchanger Materials for Advanced Solid Fuel Fired Power Plants
Authors: Mori Stefano , Pidcock Andy , Sumner Joy , Simms Nigel , Oakey John
Published: December 2021

To address the challenge of climate change, future energy systems need to have reduced greenhouse gas emissions and increased efficiencies. For solid fuel fired combustion plants, one route towards achieving this is to increase the system’s steam temperatures and pressures. Another route is to co-fire renewable fuels (such as biomass) with coals. Fireside corrosion performance of two candidate superheater/reheater alloys has been characterised at higher heat exchanger surface temperature. Samples of the alloys (a stainless steel, Sanicro 25 and a nickel-based alloy, IN740) were exposed in fireside corrosion tests at 650 °C, 700 °C and 750 °C, in controlled atmosphere furnaces using the ‘deposit recoat’ test method to simulate superheater/reheater exposure for 1000 h. After exposure, the samples were analysed using dimensional metrology to determine the extent and distributions of corrosion damage in terms of surface recession and internal damage. At 650 °C, the stainless steel and nickel-based alloy performed similarly, while at 700 °C and above, the median damage to the steel was at least 3 times greater than for the nickel-based alloy. Optical and electronic microscopy studies were used to study samples’ damage morphologies after exposure. Intergranular damage and pits were found in sample cross sections, while chromium depletion was found in areas with internal damage. For high-temperature applications, the higher cost of the nickel-based alloy could be offset by the longer life they would allow in plant with higher operating temperatures.
Climate change risk assessment for the Republic of Korea: developing a systematic assessment methodology
Authors: Song Young-Il , Lee Seunghan
Published: December 2021

Climate change risks have become a major concern of climate change adaptation, and a systematic risk assessment is required as the first step as well as a key principle of national adaptation policy processes. Although many countries conducted risk assessments, a debate over a systematic assessment process continues, and results of the risk assessment provide limited information to making adaptation policies. Based on a case study of South Korea, this research aims to establish a national-level risk assessment process which includes systematic methodologies given the current limited time/resource and insufficient climate change information. A four-step risk assessment process is proposed: (1) collecting scientific evidence, (2) making list of preliminary risks, (3) making lists of risks and prioritising the risks, (4) categorising the risks. Enough scientific evidence and data about climate change risks of Korea were retained through first two steps, and three components of risk (hazard, exposure, vulnerability) are systematically involved by assessing the magnitude and adaptive capacity of risks. As results of the risks assessment, 93 national-level climate change risks of Korea are identified, and most high priorities in risks have high risk magnitude but low adaptive capacity. This research provided insights for direction of national adaptation policy of each sector by categorising the risks into four categories.