bluuebunny/crossref_metadata_2025 huggingface dataset:
A tunable l-arabinose-inducible expression plasmid for the acetic acid bacterium Gluconobacter oxydans
Authors: Fricke Philipp Moritz , Link Tobias , Gätgens Jochem , Sonntag Christiane , Otto Maike , Bott Michael , Polen Tino
Published: September 2020

The acetic acid bacterium (AAB) Gluconobacter oxydans incompletely oxidizes a wide variety of carbohydrates and is therefore used industrially for oxidative biotransformations. For G. oxydans, no system was available that allows regulatable plasmid-based expression. We found that the l-arabinose-inducible PBAD promoter and the transcriptional regulator AraC from Escherichia coli MC4100 performed very well in G. oxydans. The respective pBBR1-based plasmids showed very low basal expression of the reporters β-glucuronidase and mNeonGreen, up to 480-fold induction with 1% l-arabinose, and tunability from 0.1 to 1% l-arabinose. In G. oxydans 621H, l-arabinose was oxidized by the membrane-bound glucose dehydrogenase, which is absent in the multi-deletion strain BP.6. Nevertheless, AraC-PBAD performed similar in both strains in the exponential phase, indicating that a gene knockout is not required for application of AraC-PBAD in wild-type G. oxydans strains. However, the oxidation product arabinonic acid strongly contributed to the acidification of the growth medium in 621H cultures during the stationary phase, which resulted in drastically decreased reporter activities in 621H (pH 3.3) but not in BP.6 cultures (pH 4.4). These activities could be strongly increased quickly solely by incubating stationary cells in d-mannitol-free medium adjusted to pH 6, indicating that the reporters were hardly degraded yet rather became inactive. In a pH-controlled bioreactor, these reporter activities remained high in the stationary phase (pH 6). Finally, we created a multiple cloning vector with araC-PBAD based on pBBR1MCS-5. Together, we demonstrated superior functionality and good tunability of an AraC-PBAD system in G. oxydans that could possibly also be used in other AAB.

Key points

• We found the AraC-PBADsystem from E. coli MC4100 was well tunable in G. oxydans.

•  In the absence of AraC orl-arabinose, expression from PBADwas extremely low.

• This araC-PBADsystem could also be fully functional in other acetic acid bacteria.
Electrical resistivity imaging for monitoring soil water motion patterns under different drip irrigation scenarios
Authors: Vanella Daniela , Ramírez-Cuesta Juan Miguel , Sacco Alessandro , Longo-Minnolo Giuseppe , Cirelli Giuseppe Luigi , Consoli Simona
Published: September 2020

The use of hydrogeophysical methods provides insights for supporting optimal irrigation design and management. In the present study, the electrical resistivity imaging (ERI) was applied for monitoring the soil water motion patterns resulting from the adoption of water deficit scenarios in a micro-irrigated orange orchard (Eastern Sicily, Italy). The relationship of ERI with independent ancillary data of soil water content (SWC), plant transpiration (T) and in situ measurements of hydraulic conductivity at saturation (Ks, i.e., using the falling head method, FH) was evaluated. The soil water motion patterns and the maximum wet depths in the soil profile identified by ERI were quite dependent on SWC (R2 = 0.79 and 0.82, respectively). Moreover, ERI was able to detect T in the severe deficit irrigation treatment (electrical resistivity increases of about 20%), whereas this phenomenon was masked at higher SWC conditions. Ks rates derived from ERI and FH approaches revealed different patterns and magnitudes among the irrigation treatments, as consequence of their different measurement scales and the methodological specificity. Finally, ERI has been proved suitable for identifying the soil wetting/drying patterns and the geometrical characteristics of wet bulbs, which represent some of the most influential variables for the optimal design and management of micro-irrigation systems.
Population pharmacokinetic analysis of phase 1 bemarituzumab data to support phase 2 gastroesophageal adenocarcinoma FIGHT trial
Authors: Xiang Hong , Liu Lucy , Gao Yuying , Ahene Ago , Macal Monica , Hsu Amy W. , Dreiling Lyndah , Collins Helen
Published: September 2020

Purpose

To report population pharmacokinetic (PK) analysis of the phase 1 study (FPA144-001, NCT02318329) and to select a clinical dose and schedule that will achieve an empirical target trough concentration (Ctrough) for an anti-fibroblast growth factor receptor 2b antibody, bemarituzumab.

Methods

Nonlinear mixed-effect modeling was used to analyse PK data. In vitro binding affinity and receptor occupancy of bemarituzumab were determined. Simulation was conducted to estimate dose and schedule to achieve an empirical target Ctrough in a phase 2 trial (FIGHT, NCT03694522) for patients receiving first-line treatment combined with modified 5-fluourouracil, oxaliplatin and leucovorin (mFOLFOX6) for gastric and gastroesophageal junction adenocarcinoma.

Results

Bemarituzumab PK is best described by a two-compartment model with parallel linear and nonlinear (Michaelis–Menten) elimination from the central compartment. Albumin, gender, and body weight were identified as the covariates on the linear clearance and/or volume of distribution in the central compartment, and no dose adjustment was warranted. An empirical target of bemarituzumab Ctrough of ≥ 60 µg/mL was projected to achieve > 95% receptor occupancy based on in vitro data. Fifteen mg/kg every 2 weeks, with a single dose of 7.5 mg/kg on Cycle 1 Day 8, was projected to achieve the target Ctrough on Day 15 in 98% of patients with 96% maintaining the target at steady state, which was confirmed in the FIGHT trial.

Conclusion

A projected dose and schedule to achieve the target Ctrough was validated in phase 1 of the FIGHT trial which supported selection of the phase 2 dose and schedule for bemarituzumab.
Performance of different Dixon-based methods for MR liver iron assessment in comparison to a biopsy-validated R2* relaxometry method
Authors: Henninger Benjamin , Plaikner Michaela , Zoller Heinz , Viveiros André , Kannengiesser Stephan , Jaschke Werner , Kremser Christian
Published: September 2020

Objectives

To prospectively evaluate a 3D-multiecho-Dixon sequence with inline calculation of proton density fat fraction (PDFF) and R2* (qDixon), and an improved version of it (qDixon-WIP), for the MR-quantification of hepatic iron in a clinical setting.

Methods

Patients with increased serum ferritin underwent 1.5-T MRI of the liver for the evaluation of hepatic iron overload. The imaging protocol for R2* quantification included as follows: (1) a validated, 2D multigradient-echo sequence (initial TE 0.99 ms, R2*-ME-GRE), (2) a 3D-multiecho-Dixon sequence with inline calculation of PDFF and R2* (initial TE 2.38 ms, R2*-qDixon), and optionally (3) a prototype (works-in-progress, WIP) version of the latter (initial TE 1.04 ms, R2*-qDixon-WIP) with improved water/fat separation and noise-corrected parameter fitting. For all sequences, three manually co-registered regions of interest (ROIs) were placed in the liver. R2* values were compared and linear regression analysis and Bland-Altman plots calculated.

Results

Forty-six out of 415 patients showed fat-water (F/W) swap with qDixon and were excluded. A total of 369 patients (mean age 52 years) were included; in 203/369, the optional qDixon-WIP was acquired, which showed no F/W swaps. A strong correlation was found between R2*-ME-GRE and R2*-qDixon (r2 = 0.92, p < 0.001) with Bland-Altman revealing a mean difference of − 3.82 1/s (SD = 21.26 1/s). Correlation between R2*-GRE-ME and R2*-qDixon-WIP was r2 = 0.95 (p < 0.001) with Bland-Altman showing a mean difference of − 0.125 1/s (SD = 30.667 1/s).

Conclusions

The 3D-multiecho-Dixon sequence is a reliable tool to quantify hepatic iron. Results are comparable with established relaxometry methods. Improvements to the original implementation eliminate occasional F/W swaps and limitations regarding maximum R2* values.

Key Points

• The 3D-multiecho-Dixon sequence for 1.5 T is a reliable tool to quantify hepatic iron.

• Results of the 3D-multiecho-Dixon sequence are comparable with established relaxometry methods.

• An improved version of the 3D-multiecho-Dixon sequence eliminates minor drawbacks.
Neuraminidase-1 promotes heart failure after ischemia/reperfusion injury by affecting cardiomyocytes and invading monocytes/macrophages
Authors: Heimerl Maren , Sieve Irina , Ricke-Hoch Melanie , Erschow Sergej , Battmer Karin , Scherr Michaela , Hilfiker-Kleiner Denise
Published: September 2020

Neuraminidase (NEU)1 forms a multienzyme complex with beta-galactosidase (β-GAL) and protective-protein/cathepsin (PPC) A, which cleaves sialic-acids from cell surface glycoconjugates. We investigated the role of NEU1 in the myocardium after ischemia/reperfusion (I/R). Three days after inducing I/R, left ventricles (LV) of male mice (3 months-old) displayed upregulated neuraminidase activity and increased NEU1, β-GAL and PPCA expression. Mice hypomorphic forneu1(hNEU1) had less neuraminidase activity, fewer pro-inflammatory (Lin−CD11b+F4/80+Ly-6Chigh), and more anti-inflammatory macrophages (Lin−CD11b+F4/80+Ly-6Clow) 3 days after I/R, and less LV dysfunction 14 days after I/R. WT mice transplanted with hNEU1-bone marrow (BM) and hNEU1 mice with WT-BM showed significantly better LV function 14 days after I/R compared with WT mice with WT-BM. Mice with a cardiomyocyte-specific NEU1 overexpression displayed no difference in inflammation 3 days after I/R, but showed increased cardiomyocyte hypertrophy, reduced expression and mislocalization of Connexin-43 in gap junctions, and LV dysfunction despite a similar infarct scar size to WT mice 14 days after I/R. The upregulation of NEU1 after I/R contributes to heart failure by promoting inflammation in invading monocytes/macrophages, enhancing cardiomyocyte hypertrophy, and impairing gap junction function, suggesting that systemic NEU1 inhibition may reduce heart failure after I/R.
Randomized Construction of Complexes with Large Diameter
Authors: Criado Francisco , Newman Andrew
Published: September 2020

We consider the question of the largest possible combinatorial diameter among pure dimensional and strongly connected $$(d-1)$$

(
d
-
1
)

-dimensional simplicial complexes on n vertices, denoted $$H_s(n, d)$$

H
s

(
n
,
d
)

. Using a probabilistic construction we give a new lower bound on $$H_s(n, d)$$

H
s

(
n
,
d
)

that is within an $$O(d^2)$$

O
(

d
2

)

factor of the upper bound. This improves on the previously best known lower bound which was within a factor of $$e^{\varTheta (d)}$$

e

Θ
(
d
)

of the upper bound. We also make a similar improvement in the case of pseudomanifolds.
Learning curve of surgical novices using the single-port platform SymphonX: minimizing OR trauma to only one 15-mm incision
Authors: Datta Rabi R. , Schönhage Sebastian , Dratsch Thomas , Toader Justus , Müller Dolores T. , Wahba Roger , Kleinert Robert , Thomas Michael , Dieplinger Georg , Stippel Dirk L. , Bruns Christiane J. , Fuchs Hans F.
Published: September 2020

Background

Minimally invasive single-port surgery is always associated with large incisions up to 2–3 cm, complicated handling due to the lack of triangulation, and instrument crossing. The aim of this prospective study was to report how medical students without any laparoscopic experience perform several laparoscopic tasks (rope pass, paper cut, peg transfer, recapping, and needle threading) with the new SymphonX single-port platform and to examine the learning curves in comparison to the laparoscopic multi-port technique.

Methods

A set of 5 laparoscopic skill tests (Rope Pass, Paper cut, Peg Transfer, Recapping, Needle Thread) were performed with 3 repetitions. Medical students performed all tests with both standard laparoscopic instruments and the new platform. Time and errors were recorded.

Results

A total of 114 medical students (61 females) with a median age of 23 years completed the study. All subjects were able to perform the skill tests with both standard laparoscopic multi-port and the single-port laparoscopic system and were able to significantly improve their performance over the three trials for all five tasks—rope pass (p < 0.001), paper cut (p < 0.001), peg transfer (p < 0.001), needle threading (p < 0.001), and recapping (p < 0.001). In 3 out of 5 tasks, medical students performed the tasks faster using the standard multi-port system—rope pass (p < 0.001), paper cut (p < 0.001), and peg transfer (p < 0.001). In the task recapping, medical students performed the task faster using the new single-port system (p = 0.003). In the task needle threading, there was no significant difference between the standard multi-port system and the new single-port system (p > 0.05).

Conclusion

This is the first study analyzing learning curves of the commercially available SymphonX platform for abdominal laparoscopic surgery when used by novices. The learning curve and the error rate are promising.
Clotting functional stability of withdrawing blood in storage for acute normovolemic hemodilution: a pilot study
Authors: Kinoshita Hirotaka , Saito Junichi , Nakai Kishiko , Noguchi Satoko , Takekawa Daiki , Tamai Yoshiko , Kitayama Masato , Hirota Kazuyoshi
Published: September 2020

Purpose

This study was conducted to time-course changes of clotting function of withdrawing blood for acute normovolemic hemodilution (ANH).

Methods

Twelve enrolled patients who underwent ANH from August, 2018 to January, 2019. Blood was withdrawn into blood collection pack and shaken at 60–80 rpm for 24 h in room temperature. Clot formation was evaluated using rotational thromboelastometry (ROTEM™) just after blood withdrawal (control) and 4, 8, 12 and 24 h after blood withdrawal. We compared with the control value and each value of extrinsically-activated test with tissue factor (EXTEM), intrinsically-activated test using ellagic acid (INTEM) and fibrin-based extrinsically activated test with tissue factor (FIBTEM).

Results

Maximum clot firmness (MCF) of FIBTEM did not change significantly. MCF of EXTEM was significantly decreased time-dependent manner but all MCF of EXTEM were within a normal range. Maximum percent change in MCF of EXTEM was 12.4% [95% confidence interval (CI): 9.0–15.8%]. The difference in the maximum clot elasticity (MCE) between EXTEM and FIBTEM (MCEEXTEM−MCEFIBTEM) was significantly decrease from 8 h after blood withdrawal. Maximum percent change in MCEEXTEM−MCEFIBTEM was 30.2% (95% CI:17.6–42.9%) at 24 h after blood withdrawal.

Conclusion

Even though the MCE significantly decreased in a time-dependent manner, MCF of FIBTEM and EXTEM was normal up to 24 h storage. The blood of ANH can use for the purpose of hemostasis at least 8 h stored at room temperature after blood withdrawal. Future studies are needed to elucidate the clinical impact on the patient after delayed transfusion of ANH blood with regard to patient’s hemostasis.
Quantitative Raman spectroscopy for the Ioncell® process: Part 2—quantification of ionic liquid degradation products and improvement of prediction performance through interval PLS
Authors: Guizani Chamseddine , Hellstén Sanna , Witos Joanna , Mäkelä Mikko , Hummel Michael , Sixta Herbert
Published: September 2020

One of the main issues associated with ionic liquids (ILs) is their recyclability. Viable recycling concepts can only be developed if one knows what is in the IL mixtures and solutions. In our previous work, we showed that it is possible to quantify water and 1.5-diazabicyclo[4.3.0]non-5-enium acetate [DBNH][OAc] IL components in liquid mixtures using Raman spectroscopy. In this regard, we considered Raman spectroscopy as a promising analytical method for the inline monitoring and control of the Ioncell® process. In the present work, we push the limits of this analytical method further by extending it to more complex and realistic liquid mixtures including the hydrolysis product 1-(3-aminopropyl)-2-pyrrolidone (APP) that can be formed upon the reaction of 5-diazabicyclo[4.3.0]non-5-ene (DBN) with water. Quantifying APP is important in order to measure the extent of the hydrolysis reaction and apply the right corrective measures to reverse the reaction and to maintain the process within the optimal working conditions. The simultaneous quantification of the four components (Acetic acid, DBN, APP and H2O) in typical Ioncell® liquid streams is investigated using Raman spectroscopy. The sensitivity of the Raman method in quantifying APP is also highlighted in comparison with refractometry, which is widely applied to measure IL concentration in aqueous mixtures. Finally, we propose simple modifications on the multivariate partial least square regression model based on a variable selection algorithm to enhance the accuracy of the predicted calibration values.
MISCELA: discovering simultaneous and time-delayed correlated attribute patterns
Authors: Harada Kei , Sasaki Yuya , Onizuka Makoto
Published: September 2020

This article addresses a new pattern mining problem in time series sensor data, which we call correlated attribute pattern mining. The correlated attribute patterns (CAPs for short) are the sets of attributes (e.g., temperature and traffic volume) on sensors that are spatially close to each other and temporally correlated in their measurements. Although the CAPs are useful to accurately analyze and understand spatio-temporal correlation between attributes, the existing mining methods are inefficient to discover CAPs because they extract unnecessary patterns. Therefore, we propose a mining method Miscela to efficiently discover CAPs. Miscela can discover not only simultaneous correlated patterns but also time delayed correlated patterns. Furthermore, we extend Miscela to automatically search for correlated patterns with any time delays. Through our experiments using three real sensor datasets, we show that the response time of Miscela is up to 20.84 times faster compared with the state-of-the-art method. We show that Miscela discovers meaningful patterns for urban managements and environmental studies.
Laterality and sex differences in the expression of brain-derived neurotrophic factor in developing rat hippocampus
Authors: Sardar Reza , Zandieh Zahra , Namjoo Zeinab , Soleimani Mansoureh , Shirazi Reza , Hami Javad
Published: September 2020

Brain-derived neurotrophic factor (BDNF), as a member of neurotrophin family, plays an important role in neurogenesis, neuronal survival and synaptic plasticity. BDNF is strongly expressed in the hippocampus, where has been associated with memory consolidation, learning, and cognition. In this study, Real-time PCR, immunohistochemistry, and stereology were used to evaluate the gender differences and left-right asymmetries in the expression of BDNF in the developing rat hippocampus during the neurogenesis-active period, at postnatal days P0, P7 and P14. We found the lowest expression of BDNF in the right side and the highest in the left side hippocampi of both male and female neonates at P14 (P ≤ 0.05 each). At the same time, there were significant differences in the hippocampal expression of BDNF between males and females (P ≤ 0.05 each). No important differences in the number of BDNF expressing neurons in different subregions of right/left hippocampus were observed between male and female animals at P0 and P7 (P > 0.05). Furthermore, the highest numerical density of BDNF positive cells was detected in the both sides hippocampal CA1 in the male/female offspring at P7, and in the CA2, CA3 and dentate gyrus at P14 (P ≤ 0.05 each). Based on these findings, it can be concluded that there are prominent sex and interhemispheric differences in the expression of BDNF in the developing rat hippocampus, suggesting a probable mechanism for the control of gender and laterality differences in development, structure, and function of the hippocampus.
Immunity to wh-misidentification
Authors: McGlynn Aidan
Published: September 2020

This paper responds to arguments due to Joel Smith and Annalisa Coliva that try to show that James Pryor’s notion of wh-misidentification is philosophically uninteresting, and perhaps even spurious. It also proposes definitions of wh-misidentification and immunity to wh-misidentification which try to improve in various ways on the characterisations that standardly figure in the literature, and explores the relationship between misidentification and the epistemic structures characteristic of some kinds of Gettier cases.
Differentiation of Cells Isolated from Afterbirth Tissues into Hepatocyte-Like Cells and Their Potential Clinical Application in Liver Regeneration
Authors: Michalik Marcin , Gładyś Aleksandra , Czekaj Piotr
Published: September 2020

Toxic, viral and surgical injuries can pose medical indications for liver transplantation. The number of patients waiting for a liver transplant still increases, but the number of organ donors is insufficient. Hepatocyte transplantation was suggested as a promising alternative to liver transplantation, however, this method has some significant limitations. Currently, afterbirth tissues seem to be an interesting source of cells for the regenerative medicine, because of their unique biological and immunological properties. It has been proven in experimental animal models, that the native stem cells, and to a greater extent, hepatocyte-like cells derived from them and transplanted, can accelerate regenerative processes and restore organ functioning. The effective protocol for obtaining functional mature hepatocytes in vitro is still not defined, but some studies resulted in obtaining functionally active hepatocyte-like cells. In this review, we focused on human stem cells isolated from placenta and umbilical cord, as potent precursors of hepatocyte-like cells for regenerative medicine. We summarized the results of preclinical and clinical studies dealing with the introduction of epithelial and mesenchymal stem cells of the afterbirth origin to the liver failure therapy. It was concluded that the use of native afterbirth epithelial and mesenchymal cells in the treatment of liver failure could support liver function and regeneration. This effect would be enhanced by the use of hepatocyte-like cells obtained from placental and/or umbilical stem cells.
Adaptivität im Sportunterricht in selbstständigen Arbeitsphasen messen
Authors: Wibowo Jonas
Published: September 2020

Adaptives Unterrichten wird als ein vielversprechender Ansatz gesehen, um mit der großen interindividuellen Vielfalt unter den Schüler*innen im Sportunterricht umzugehen. Die Bedeutung der Thematik ergibt sich einerseits aus der gleichstellungspolitischen Forderung einer individuellen Förderung, aber auch aus einer lern- und bildungstheoretischen Notwendigkeit, Lernumgebungen an individuelle Bedürfnisse anzupassen, um Lern- und Bildungsprozesse zu unterstützen. Dabei gilt die Passung zwischen der Instruktion der Lehrperson und den Voraussetzungen der Schüler*innen als zentrales Gütekriterium für den Umgang mit Heterogenität. Die Forschungslandschaft zu der Thematik ist durch eine enorme Vielfalt in Bezug auf die Auslegung von und den forschungsmethodischen Zugang zu adaptivem Unterrichten geprägt. In dem Beitrag werden ein Ansatz zur standardisierten Beobachtung der Passung zwischen der lehrpersonseitigen Instruktion und den Lernaktivitäten der Schüler*innen sowie Ergebnisse einer Pilotierungsstudie vorgestellt. Passung (Contingency) wird dabei als Verhältnis von Instruktionen zu vorangegangen Lernaktivitäten operationalisiert. Die Ergebnisse der Pilotierung deuten darauf hin, dass das Kodierverfahren zuverlässig ist (Cohen’s Kappa: 0,7–0,96) und im beobachteten Unterricht der sechs Lehrpersonen Contingency bei bestimmten Lernaktivitäten (niedrige Autonomie) eher auftritt als bei anderen (hohe Autonomie).
Identification of Pavement Model Parameters in the Area of Discontinuous Surface Deformation Based on FWD Tests
Authors: Grygierek Marcin , J. Sternik Krzysztof
Published: September 2020

Determination of the parameters of the pavement model in the linear discontinuous surface deformation (LDSD) area is presented in the article. The values are based on back calculations which involve results obtained from the elastic half-space model and the elastic—perfectly plastic model implemented in the finite element code compared with the results of the pavement deflection measured with Falling Weight Deflectometer (FWD). Based on the results of the calculations which have been matched to the results of the in situ measurements, the obtained values of the parameters of the pavement model within LDSD zone and outside it, were analysed. The results of pavement tests indicate at least a threefold increase in pavement deflections in the discontinuous deformation zone compared to deflections in the sections not affected by LDSD. The results of in situ tests and computational analysis presented in the paper allow their use in pavement reinforcement design in the area of anticipated LDSD.
A new statistic for detecting outliers in Rayligh distribution
Authors: Deiri Einolah
Published: September 2020

Zerbet and Nikulin (Commun Statist Theor Meth 32(3): 573–583, 2003) presented the new statistic $${Z}_{k}$$

Z
k

for detecting outliers in exponential distribution. They also compared this statistic with Dixon's statistic $${D}_{k}$$

D
k

. Jabbari et al. (Commun Statist Theor Meth 39(4): 698–706, 2010) expend this statistic ($${Z}_{k}$$

Z
k

) for Gamma distribution. In this paper, we generalize statistics $${Z}_{k}$$

Z
k

–$${Z}_{k}^{*}$$

Z

k

∗

, for detecting outliers in Rayligh distribution and compare the results with the generalized Dixon's statistic. Distribution of the test based on the statistic $${Z}_{k}^{*}$$

Z

k

∗

under slippage alternatives is obtained. The criterion value and power of the new test are also calculated and compared with the criterion value of the Dixon's statistic. The results show that the test based on statistic $${Z}_{k}^{*}$$

Z

k

∗

is more powerful than the test based on the statistic $${D}_{k}$$

D
k

.
Covid-19 and the Epigenetics of Learning
Authors: Johnson Mark William , Maitland Elizabeth , Torday John
Published: September 2020

Covid-19 is a natural phenomenon that has rapidly upended much of the cultural infrastructure of societies across the globe. Education, which in recent years increasingly tied itself to notions of global culture and markets, is deeply threatened by these changes to the natural environment. This paper makes the case that the relationship between nature and culture in education requires a deep level analysis of the biological and physical substrate of human learning. Only with a sufficiently fundamental level of analysis can society reorganise its systems of learning and scientific inquiry to this rapidly changing environment. Drawing on evolutionary biology, we argue that institutional and individual structures and processes are recapitulations of evolutionary cellular development. Understanding the impact of Covid-19 on cells presents an invitation to consider the larger-scale cultural recapitulations of similar mechanisms and structures, and this has implications for the ways education might most effectively deploy technology. Whilst universities seek to maintain their existing structures, practices and business models, a cellular evolutionary approach points to the necessity for fundamental rethinking of intellectual life and learning. We consider the parameters of effective educational organisation in a post-Covid-19 world. As the richness and variety of the physical campus is removed, viable educational relationships will necessitate deeper intellectual connections and personal inquiries than are currently permitted in the transactional processes of education.
Investigation of material removal characteristics of Si (100) wafer during linear field atmospheric-pressure plasma etching
Authors: Guo Weijia , A. Senthil Kumar , Xu Peng
Published: September 2020

Atmospheric-pressure (AP) plasma etching provides an alternative method for mechanical grinding to realize wafer thinning of Si wafer. It can avoid the damages and micro-cracks that would be introduced by mechanical stress during the grinding process. In this study, the material removal characteristics of Si (100) wafer processed by linear field AP plasma generated using carbon tetrafluoride (CF4) as the reactive source were analyzed. This linear field plasma etching tool has a typical removal profile and the depth removal rate that can reach up to 1.082 μm/min. The effect of O2 concentration on the removal rate was discussed and the surface morphology during the process was characterized using scanning electron microscopy. It is shown that the subsurface damage layer was gradually removed during the etching process and the surface was observed to be smoothened with the increase of the etching depth. This present work contributes a basic understanding of the linear field AP plasma etching performance with different gas composition and the typical characteristics would be further applied to damage-free precision removal of Si.
Supporting designers: moving from method menagerie to method ecosystem
Authors: Gericke Kilian , Eckert Claudia , Campean Felician , Clarkson P. John , Flening Elias , Isaksson Ola , Kipouros Timos , Kokkolaras Michael , Köhler Christian , Panarotto Massimo , Wilmsen Miriam
Published: September 2020

Supporting designers is one of the main motivations for design research. However, there is an ongoing debate about the ability of design research to transfer its results, which are often provided in form of design methods, into practice. This article takes the position that the transfer of design methods alone is not an appropriate indicator for assessing the impact of design research by discussing alternative pathways for impacting design practice. Impact is created by different means – first of all through the students that are trained based on the research results including design methods and tools and by the systematic way of thinking they acquired that comes along with being involved with research in this area. Despite having a considerable impact on practice, this article takes the position that the transfer of methods can be improved by moving from cultivating method menageries to facilitating the evolution of method ecosystems. It explains what is understood by a method ecosystem and discusses implications for developing future design methods and for improving existing methods. This paper takes the position that efforts on improving and maturing existing design methods should be raised to satisfy the needs of designers and to truly support them.
Inessential directed maps and directed homotopy equivalences
Authors: Raussen Martin
Published: September 2020

A directed space is a topological space $X$ together with a subspace $\vec {P}(X)\subset X^I$ of directed paths on $X$. A symmetry of a directed space should therefore respect both the topology of the underlying space and the topology of the associated spaces $\vec {P}(X)_-^+$ of directed paths between a source ($-$) and a target ($+$)—up to homotopy. If it is, moreover, homotopic to the identity map—in a directed sense—such a symmetry will be called an inessential d-map, and the paper explores the algebra and topology of inessential d-maps. Comparing two d-spaces $X$ and $Y$ ‘up to symmetry’ yields the notion of a directed homotopy equivalence between them. Under appropriate conditions, all directed homotopy equivalences are shown to satisfy a 2-out-of-3 property. Our notion of directed homotopy equivalence does not agree completely with the one defined in Goubault (2017, arxiv:1709:05702v2) and Goubault, Farber and Sagnier (2020, J. Appl. Comput. Topol. 4, 11–27); the deviation is motivated by examples. Nevertheless, directed topological complexity, introduced in Goubault, Farber and Sagnier (2020) is shown to be invariant under our notion of directed homotopy equivalence. Finally, we show that directed homotopy equivalences result in isomorphisms on the pair component categories of directed spaces introduced in Goubault, Farber and Sagnier (2020).
A new approach to assessing shyness of college students using computerized adaptive testing: CAT-Shyness
Authors: Li Zifei , Cai Yan , Tu Dongbo
Published: September 2020

Assessing shy symptoms via computerized adaptive testing (CAT) provides greater measurement precision coupled with a lower test burden compared to conventional tests. The computerized adaptive test for shyness (CAT-Shyness) was developed based on a large sample of 1400 participants from China. Item bank development included the investigation of unidimensionality, local independence, and exploration of differential item functioning (DIF). CAT simulations based on the real data were carried out to investigate the reliability, validity, and predicted utility (sensitivity and specificity) of the CAT-Shyness. The CAT-Shyness item bank was successfully built and proved to have excellent psychometric properties: high content validity, unidimensionality, local independence, and no DIF. The CAT simulations needed 14 items to achieve a high measurement precision with a reliability of .9. Moreover, the results revealed that the proposed CAT-Shyness had acceptable and reasonable marginal reliability, criterion-related validity, and sensitivity and specificity. It not only had acceptable psychometric properties, but also had a shorter but efficient assessment of shyness, which can save significant test time and reduce the test burden for individuals with less information loss.
Law and Moral Regulation in Modern Egypt:Ḥisbafrom Tradition to Modernity
Authors: Ezzat Ahmed
Published: September 2020

This article examines the historical roots of juridical moral regulation in modern Egypt, assessing the relationship between modern law and shariʿa through the lens of the influence of the Islamic practice ofḥisbaon courts and legislators. The article engages critically with scholarship on Islamic law and postcolonial theory regarding the impact of Western colonialism on law in Muslim societies and problematizes the understanding that shariʿa was secularized in the Egyptian legal culture through the translation of Western legal concepts. Instead, a different narrative is offered, one that recognizes the agency of local actors in the process of secularization and considers the influence of shariʿa in the legal development of contemporary Egypt.
Subgenual activation and the finger of blame: individual differences and depression vulnerability
Authors: Lythe Karen E , Gethin Jennifer A , Workman Clifford I , Lambon Ralph Matthew A. , Deakin John F.W. , Moll Jorge , Zahn Roland
Published: September 2020

Background

Subgenual cingulate cortex (SCC) responses to self-blaming emotion-evoking stimuli were previously found in individuals prone to self-blame with and without a history of major depressive disorder (MDD). This suggested SCC activation reflects self-blaming emotions such as guilt, which are central to models of MDD vulnerability.

Method

Here, we re-examined these hypotheses in an independent larger sample. A total of 109 medication-free participants (70 with remitted MDD and 39 healthy controls) underwent fMRI whilst judging self- and other-blaming emotion-evoking statements. They also completed validated questionnaires of proneness to self-blaming emotions including those related to internal (autonomy) and external (sociotropy) evaluation, which were subjected to factor analysis.

Results

An interaction between group (remitted MDD v. Control) and condition (self- v. other-blame) was observed in the right SCC (BA24). This was due to higher SCC signal for self-blame in remitted MDD and higher other-blame-selective activation in Control participants. Across the whole sample, extracted SCC activation cluster averages for self- v. other-blame were predicted by a regression model which included the reliable components derived from our factor analysis of measures of proneness to self-blaming emotions. Interestingly, this prediction was solely driven by autonomy/self-criticism, and adaptive guilt factors, with no effect of sociotropy/dependency.

Conclusions

Despite confirming the prediction of SCC activation in self-blame-prone individuals and those vulnerable to MDD, our results suggest that SCC activation reflects blame irrespective of where it is directed rather than selective for self. We speculate that self-critical individuals have more extended SCC representations for blame in the context of self-agency.
Tailoring cognitive behavioural therapy to subtypes of voice-hearing using a novel tabletised manual: a feasibility study
Authors: Dodgson Guy , Alderson-Day Ben , Smailes David , Ryles Faye , Mayer Claire , Glen-Davison Joanne , Mitrenga Kaja , Fernyhough Charles
Published: September 2020

Background:

Cognitive behavioural therapy for psychosis (CBTp) is a recommended treatment for psychotic experiences, but its effectiveness has been questioned. One way of addressing this may be to tailor therapy materials to the phenomenology of specific psychotic experiences.

Aim:

In this study, we investigated the acceptability of a novel treatment manual for subtypes of ‘voice-hearing’ experiences (i.e. auditory verbal hallucinations). An uncontrolled, single-arm design was used to assess feasibility and acceptability of using the manual in routine care for people with frequent voice-hearing experiences.

Method:

The manual was delivered on a smart tablet and incorporated recent research evidence and theory into its psychoeducation materials. In total, 24 participants completed a baseline assessment; 19 started treatment, 15 completed treatment and 12 participants completed a follow-up assessment (after 10 sessions of using the manual).

Results:

Satisfaction with therapy scores and acceptability ratings were high, while completion rates suggested that the manual may be more appropriate for help with participants from Early Intervention in Psychosis services rather than Community Mental Health Teams.

Conclusion:

Within-group changes in symptom scores suggested that overall symptom severity of hallucinations – but not other psychosis features, or beliefs about voices – are likely to be the most appropriate primary outcome for further evaluation in a full randomised controlled trial.
Poor appetite and overeating reported by adults in Australia during the coronavirus-19 disease pandemic: a population-based study
Authors: Owen AJ , Tran T , Hammarberg K , Kirkman M , Fisher JRW
Published: September 2020

Objective:

As a result of the coronavirus-19 disease (COVID-19) pandemic, Australia adopted emergency measures on 22 March 2020. This study reports the effect of the COVID-19 lockdown on appetite and overeating in Australian adults during the first month of emergency measures.

Design:

This study reports analysis of data from the population-based, self-completed survey. The main outcome measure was an item from the Patient Health Questionnaire 9 asking: ‘Over the past 2 weeks, how often have you been bothered by poor appetite or overeating?’. Data on sociodemographic factors, symptoms of anxiety and depression, and the impact of COVID-19 and lockdown were also collected. Multivariable logistic regression was used to examine associations with poor appetite or overeating.

Setting:

An anonymous online survey available from 3 April to 2 May 2020.

Participants:

A total of 13 829 Australian residents aged 18 years or over.

Results:

The weighted prevalence of being bothered by poor appetite or overeating in the past 2 weeks was 53·6 %, with 11·6 % (95 % CI 10·6, 12·6) of the cohort reporting poor appetite or overeating nearly every day. High levels of anxiety, concern about contracting COVID-19, being in lockdown with children and reporting a severe impact of the lockdown were associated with increased odds of poor appetite or overeating.

Conclusions:

Given the widespread prevalence of being bothered by poor appetite or overeating, universal public health interventions to address emotion-focused or situational eating during periods of lockdown may be appropriate.
Government Transfers and Poverty Alleviation among Older Adults in the United States from 2002 to 2014
Authors: Lu Peiyi , Shelley Mack , Liu Yi-Long
Published: September 2020

Studies have indicated government transfers greatly alleviate poverty among older Americans. Yet recent social policy changes were suggested to increase older Americans’ fiscal insecurity. New evidence is needed to expand the evaluation of government transfers. Longitudinal Health and Retirement Study data from 2002 to 2014 were used. We computed individuals’ poverty status both when household income included and did not include government transfers. Results indicated the poverty rate dropped dramatically when household income included government transfers. The poverty alleviation effect was significantly greater among people who were female, older, members of a minority group, having fewer years of education, residing in the South, and living in a bigger household. Evidence from this study solidified the overall poverty alleviation effect of government transfers in old age. Differential effects among various demographic groups could be attributed to their initial status and divergent political beliefs about who should receive government transfers.
Podcast: The Unusual Relationship Between Climate and Pandemics
Authors: Lipuma Lauren
Published: September 2020

Two recent studies show how climate affects human pandemics and how pandemics, in turn, alter the environment.
Martian Ripples Making a Splash
Authors: Lorenz Ralph D.
Published: September 2020

New work by Sullivan et al. (2020, https://doi.org.10.1029/2020JE006485) shows that ripples of Martian sediments can have a wide range of sizes and calls into question a proposed fluid drag mechanism and interpretations therefrom on Mars paleoclimate.
The Postglacial Isotopic Record of Intermediate Water Connects Mediterranean Sapropels and Organic‐Rich Layers
Authors: Incarbona Alessandro , Sprovieri Mario
Published: September 2020

Carbon‐rich layers exist at both sides of the Mediterranean Sea sedimentary record and are called sapropels and organic rich layers (ORLs), respectively, in the eastern and western basins. They have different levels of organic carbon accumulation and seafloor oxygen deprivation. The most recent sapropel and ORL depositions have a different timing, approximately 10.8–6.1 and 14.5–9.0 ka, respectively. Here we investigate oxygen isotopic records of three foraminifera species that occupy different habitats within the Sicily Channel water column since ~12.0 ka, thus in the sill between the eastern and western Mediterranean basins. These data are ice volume corrected, to get information on water masses density variability, and are accompanied by benthic foraminifera δ13C measurements to establish Sicily Channel seafloor ventilation. Our results, and the comparison with other chronologically well‐constrained Mediterranean records, highlight the connection of the two subbasins due to monsoon activity. The end of the maximum Nile River flooding at ~9.2 ka, and eastern Mediterranean seafloor reventilation above 1,800–1,500 m depth at ~ 8.2 and 7.2 ka, left a clear signature in the intermediate water isotopic record of the Sicily Channel. Concurrently, the western Mediterranean deep water circulation experienced a significant recovery after a long period of slowdown. We argue that African monsoon weakening was transmitted into the western Mediterranean, through the intermediate layer of circulation, where deep water formation took place and brought oxygen to the seafloor.
EGFR activity addiction facilitates anti-ERBB based combination treatment of squamous bladder cancer
Authors: Rose Michael , Maurer Angela , Wirtz Julia , Bleilevens Andreas , Waldmann Tanja , Wenz Maximilian , Eyll Marie , Geelvink Mirja , Gereitzig Melanie , Rüchel Nadine , Denecke Bernd , Eltze Elke , Herrmann Edwin , Toma Marieta , Horst David , Grimm Tobias , Denzinger Stefan , Ecke Thorsten , Vögeli Thomas Alexander , Knuechel Ruth , Maurer Jochen , Gaisa Nadine T.
Published: September 2020

Recent findings suggested a benefit of anti-EGFR therapy for basal-like muscle-invasive bladder cancer (MIBC). However, the impact on bladder cancer with substantial squamous differentiation (Sq-BLCA) and especially pure squamous cell carcinoma (SCC) remains unknown. Therefore, we comprehensively characterized pure and mixed Sq-BLCA (n = 125) on genetic and protein expression level, and performed functional pathway and drug-response analyses with cell line models and isolated primary SCC (p-SCC) cells of the human urinary bladder. We identified abundant EGFR expression in 95% of Sq-BLCA without evidence for activating EGFR mutations. Both SCaBER and p-SCC cells were sensitive to EGFR tyrosine kinase inhibitors (TKIs: erlotinib and gefitinib). Combined treatment with anti-EGFR TKIs and varying chemotherapeutics led to a concentration-dependent synergism in SCC cells according to the Chou-Talalay method. In addition, the siRNA knockdown of EGFR impaired SCaBER viability suggesting a putative “Achilles heel” of Sq-BLCA. The observed effects seem Sq-BLCA-specific since non-basal urothelial cancer cells were characterized by poor TKI sensitivity associated with a short-term feedback response potentially attenuating anti-tumor activity. Hence, our findings give further insights into a crucial, Sq-BLCA-specific role of the ERBB signaling pathway proposing improved effectiveness of anti-EGFR based regimens in combination with chemotherapeutics in squamous bladder cancers with wild-type EGFR-overexpression.
The Greatwall kinase safeguards the genome integrity by affecting the kinome activity in mitosis
Authors: Bisteau Xavier , Lee Joann , Srinivas Vinayaka , Lee Joanna H. S. , Niska-Blakie Joanna , Tan Gifford , Yap Shannon Y. X. , Hom Kevin W. , Wong Cheng Kit , Chae Jeongjun , Wang Loo Chien , Kim Jinho , Rancati Giulia , Sobota Radoslaw M. , Tan Chris S. H. , Kaldis Philipp
Published: September 2020

Progression through mitosis is balanced by the timely regulation of phosphorylation and dephosphorylation events ensuring the correct segregation of chromosomes before cytokinesis. This balance is regulated by the opposing actions of CDK1 and PP2A, as well as the Greatwall kinase/MASTL. MASTL is commonly overexpressed in cancer, which makes it a potential therapeutic anticancer target. Loss ofMastlinduces multiple chromosomal errors that lead to the accumulation of micronuclei and multilobulated cells in mitosis. Our analyses revealed that loss ofMastlleads to chromosome breaks and abnormalities impairing correct segregation. Phospho-proteomic data forMastlknockout cells revealed alterations in proteins implicated in multiple processes during mitosis including double-strand DNA damage repair. In silico prediction of the kinases with affected activity unveiled NEK2 to be regulated in the absence ofMastl. We uncovered that, RAD51AP1, involved in regulation of homologous recombination, is phosphorylated by NEK2 and CDK1 but also efficiently dephosphorylated by PP2A/B55. Our results suggest thatMastlKOdisturbs the equilibrium of the mitotic phosphoproteome that leads to the disruption of DNA damage repair and triggers an accumulation of chromosome breaks even in noncancerous cells.