bluuebunny/crossref_metadata_2025 huggingface dataset:
Economic and Investment Opportunities
Authors: Williams J. E. D.
Published: July 2022

Economic and investment opportunities in the light of, the Edwards Report! The subject must have been devised by an engineer. I do not understand it. What can economic opportunities mean? Economics is concerned with finding how best to apply the finite resources of mankind to its infinite wants. What opportunities of this kind does this Report give us? I think it will help make air transport more economic through its educating influence, principally on the powers-that-be.
The British Aircraft Manufacturing Industry
Authors: Newman D. R.
Published: July 2022

The theme of the meeting poses the question, “Is there a future for British Air Transport ?” I firmly believe that the answer to this question is “Yes, of course there is,” and that the only debatable issue is the size and vigour of the future British Air Transport Industry.
Aero-Thermo-Structural Optimisation in Radome Design
Authors: Wooldridge M. J.
Published: July 2022

The design of a homing missile normally involves the incorporation of a dielectric window to form the nose region of the flight vehicle. Immediately this creates a situation in which a compromise is required between the conflicting needs of

(a)

The aerodynamicist who requires a fairing of minimum drag, within the length limitations imposed, and which at the same time possesses a reasonably predictable shape. The shape must often satisfy rain erosion requirements.

(b)

The heat transfer engineer who requires that the thermal load be spread as uniformly as possible over the fairing surface.

(c)

The materials/structures technologist who requires the fairing to be manufactured from readily available material at reasonable cost.

(d)

The microwave engineer who requires no fairing at all.
Vortex Structures in Turbulent Boundary Layers
Authors: Clark J. A. , Markland E.
Published: July 2022

The structure of turbulent boundary layers has recently been studied in detail. Using the hydrogen, bubble technique, Kline et al have detected intermittent formation of low-speed streaks very close to the surface, which lift away, thereby forming local inflexions in the velocity profile. These amplify disturbances, producing eddies which are ejected into the outer part of the layer. Black has proposed a turbulence model consisting of periodic horseshoe vortices within the layer, in which the longitudinal legs are stretched as they move through the comparatively quiescent layer.
Project Management—A Science, An Art or An Organisation Problem
Authors: Hardy D. M.
Published: July 2022

Air Cdre. Harland dealt with Project Management at Mintech, and Mr. Keenan described a type of Project Management in an aero engine firm.

Before considering other types of project organisation which can be used by the aircraft manufacturer, I should like to take a broad look at Project Management in relation to an aircraft weapon system required for the British Services. I should like to mention all the agencies involved in achieving the aim of producing an aircraft to meet the specification at the right time and cost since, as Air Cdre. Harland said, what is required is teamwork and mutual confidence between all agencies concerned.
On the Deformation of Parallelogrammic Sandwich Panels
Authors: Kennedy J. B.
Published: July 2022

Sandwich panels are utilised quite often in aircraft and missile structures mainly because of their high strength to weight ratio. The core of the panel, made of light material such as balsa wood or synthetic material, stabilises the face skin sheet which is usually metallic, and contributes to the shear strength of the section.

Rectangular sandwich panels have been analysed by various investigators. In particular, Reissner deduced the range of linearity of deflections as a function of the core rigidity relative to that of the face skin. Results for parallelogrammic sandwich panels, however, are not available.
Predicting states of elevated negative affect in adolescents from smartphone sensors: a novel personalized machine learning approach
Authors: Ren Boyu , Balkind Emma G. , Pastro Brianna , Israel Elana S. , Pizzagalli Diego A. , Rahimi-Eichi Habiballah , Baker Justin T. , Webb Christian A.
Published: July 2022

Background

Adolescence is characterized by profound change, including increases in negative emotions. Approximately 84% of American adolescents own a smartphone, which can continuously and unobtrusively track variables potentially predictive of heightened negative emotions (e.g. activity levels, location, pattern of phone usage). The extent to which built-in smartphone sensors can reliably predict states of elevated negative affect in adolescents is an open question.

Methods

Adolescent participants (n = 22; ages 13–18) with low to high levels of depressive symptoms were followed for 15 weeks using a combination of ecological momentary assessments (EMAs) and continuously collected passive smartphone sensor data. EMAs probed negative emotional states (i.e. anger, sadness and anxiety) 2–3 times per day every other week throughout the study (total: 1145 EMA measurements). Smartphone accelerometer, location and device state data were collected to derive 14 discrete estimates of behavior, including activity level, percentage of time spent at home, sleep onset and duration, and phone usage.

Results

A personalized ensemble machine learning model derived from smartphone sensor data outperformed other statistical approaches (e.g. linear mixed model) and predicted states of elevated anger and anxiety with acceptable discrimination ability (area under the curve (AUC) = 74% and 71%, respectively), but demonstrated more modest discrimination ability for predicting states of high sadness (AUC = 66%).

Conclusions

To the extent that smartphone data could provide reasonably accurate real-time predictions of states of high negative affect in teens, brief ‘just-in-time’ interventions could be immediately deployed via smartphone notifications or mental health apps to alleviate these states.
Smooth toolpath interpolation for a 5-axis hybrid machine tool
Authors: He Zhen , Fang Hanliang , Bao Yufei , Yang Fufu , Zhang Jun
Published: July 2022

Due to the merits of high rigidity and good dynamics, hybrid machine tools have been gradually applied to efficient machining of thin-walled workpiece with complex geometries. However, the discontinuity of tangential component of toolpath in hybrid machine tools may cause velocity fluctuations, leading to poor surface quality of workpiece. In this paper, a novel 5-axis hybrid machine tool is taken as an example to demonstrate a smooth toolpath interpolation method. First, an adaptive acceleration and deceleration control algorithm is presented to realize the smooth transition between two constrained velocity points. Second, a spline curve-based interpolation algorithm is proposed to realize the smoothness of the trajectory. Meanwhile, a parameter synchronization method is proposed to ensure the synchronization of the interpolated tool-axis vector and the interpolated tool tip. Thirdly, an inverse kinematic analysis is conducted based on an inverse position solution model and a velocity mapping model. Finally, a set of machining tests on S-shape workpiece in line with the ISO standard is carried out to verify the effectiveness of the proposed smooth toolpath interpolation method.
A class of spatial remote center-of-motion mechanisms and its forward kinematics
Authors: Bian Yuan , Zhao Jianchang , Li Jinhua , Wei Guowu , Li Jianmin
Published: July 2022

Robot-assisted minimally invasive surgery (MIS) has shown tremendous advances over the traditional technique. A crucial challenge for developing a MIS robot is the kinematic design of the remote center-of-motion (RCM) mechanism. In this paper, a class of spatial RCM mechanism is analyzed. They are obtained by generating virtual parallelograms. The main process is to construct a line that passes through a fixed point under the mechanical constraint. The axis of the surgical tool is then constrained to parallel with that line. Hence, due to the geometrical feature of the parallel lines, the axis of the surgical tool will always pass through a fixed point, i.e., the RCM point. Due to the specially designed structure, the fixed point does not need to be physically belonging to the mechanism. The geometrical analysis method is employed to obtain the closed-form solution of the forward kinematics of the proposed mechanisms. Due to the high load capacity of parallel mechanism, the robots based on the proposed RCM mechanisms have promising applications as an external positioner to be used in robotic single-port surgeries.
ESTIMATION AND INFERENCE WITH NEAR UNIT ROOTS
Authors: Phillips Peter C.B.
Published: July 2022

New methods are developed for identifying, estimating, and performing inference with nonstationary time series that have autoregressive roots near unity. The approach subsumes unit-root (UR), local unit-root (LUR), mildly integrated (MI), and mildly explosive (ME) specifications in the new model formulation. It is shown how a new parameterization involving a localizing rate sequence that characterizes departures from unity can be consistently estimated in all cases. Simple pivotal limit distributions that enable valid inference about the form and degree of nonstationarity apply for MI and ME specifications and new limit theory holds in UR and LUR cases. Normalizing and variance stabilizing properties of the new parameterization are explored. Simulations are reported that reveal some of the advantages of this alternative formulation of nonstationary time series. A housing market application of the methods is conducted that distinguishes the differing forms of house price behavior in Australian state capital cities over the past decade.
Ordered multi-state system signature and its dynamic version in evaluating used multi-state systems
Authors: Yi He , Balakrishnan Narayanaswamy , Li Xiang
Published: July 2022

Signature theory plays an important part in the field of reliability. In this paper, the ordered multi-state system signature and its related properties are discussed based on a life-test of independent and non-identical coherent or mixed systems with independent and identical binary-state components. Dynamic properties of these systems are considered through a new notion called dynamic multi-state system signature, and then related comparisons are made based on system lifetimes and costs. Finally, the theoretical results established are illustrated with some specific examples to demonstrate the use of dynamic ordered multi-state system signature in evaluating used multi-state coherent or mixed systems.
ETR German within the system of language variation
Authors: Hennig Mathilde
Published: July 2022

The paper discusses whether easy-to-read (ETR) German can be classified as a ‘variety’ and/or a ‘register’. It appears to be very difficult to capture the variational status of ETR German within the system of language variation due to its rather artificial, rule-based character. On the other hand, the question of whether the notion of variety or register, or any other notion modelling language variation, is suitable for the linguistic classification of ETR German very much depends on how these notions are defined. Thus the article reveals general difficulties in capturing the functioning of language variation with clear-cut definitions and concepts due to the dynamics and complexity of language variation as such. Nevertheless, the explanatory frameworks of concepts such as variety and register prove to be useful for describing the special variational status of ETR German.
Reduced FMR1 mRNA translation efficiency in Fragile X patients
with premutations
Authors: PRIMERANO BEATRICE , TASSONE FLORA , HAGERMAN RANDI J. , HAGERMAN PAUL , AMALDI FRANCESCO , BAGNI CLAUDIA
Published: July 2022

The Fragile X mental retardation gene (FMR1)
contains a polymorphic trinucleotide CGG repeat in the 5′ untranslated
region (UTR) of the FMR1 messenger. We have
characterized three lymphoblastoid cell lines derived from unrelated male
carriers of a premutation that overexpress FMR1
mRNA and show reduced FMRP level compared to normal cells. The analysis of
polysomes/mRNPs distribution of mRNA in the cell lines with a premutation
shows that the polysomal association of FMR1
mRNA, which is high in normal cells, becomes progressively lower with
increasing CGG repeat expansion. In addition, we could detect a very low
level of FMR1 mRNA in a lymphoblastoid cell line
from a patient with a full mutation. In this case,
FMR1 mRNA is not at all associated with
polysomes, in agreement with the complete absence of FMRP. The impairment of
FMR1 mRNA translation in patients with the
Fragile X syndrome with FMR1 premutation is the
cause of the lower FMRP levels that leads to the clinical
involvement.
The influence of viral coding sequences on pestivirus IRES activity
reveals further parallels with translation initiation in prokaryotes
Authors: FLETCHER SIMON P. , ALI IRAJ K. , KAMINSKI ANN , DIGARD PAUL , JACKSON RICHARD J.
Published: July 2022

Classical swine fever virus (CSFV) is a member of the pestivirus family,
which shares many features in common with hepatitis C virus (HCV). It is
shown here that CSFV has an exceptionally efficient
cis-acting internal ribosome entry segment
(IRES), which, like that of HCV, is strongly influenced by the sequences
immediately downstream of the initiation codon, and is optimal with viral
coding sequences in this position. Constructs that retained 17 or more
codons of viral coding sequence exhibited full IRES activity, but with only
12 codons, activity was ∼66% of maximum in vitro (though close to maximum in
transfected BHK cells), whereas with just 3 codons or fewer, the activity
was only ∼15% of maximum. The minimal coding region elements required for
high activity were exchanged between HCV and CSFV. Although maximum activity
was observed in each case with the homologous combination of coding region
and 5′ UTR, the heterologous combinations were sufficiently active to rule
out a highly specific functional interplay between the 5′ UTR and coding
sequences. On the other hand, inversion of the coding sequences resulted in
low IRES activity, particularly with the HCV coding sequences. RNA structure
probing showed that the efficiency of internal initiation of these chimeric
constructs correlated most closely with the degree of single-strandedness of
the region around and immediately downstream of the initiation codon. The
low activity IRESs could not be rescued by addition of supplementary eIF4A
(the initiation factor with ATP-dependent RNA helicase activity). The
extreme sensitivity to secondary structure around the initiation codon is
likely to be due to the fact that the eIF4F complex (which has eIF4A as one
of its subunits) is not required for and does not participate in initiation
on these IRESs.
Detailed analysis of RNA–protein interactions within the bacterial
ribosomal protein L5/5S rRNA complex
Authors: PEREDERINA ANNA , NEVSKAYA NATALIA , NIKONOV OLEG , NIKULIN ALEXEI , DUMAS PHILIPPE , YAO MIN , TANAKA ISAO , GARBER MARIA , GONGADZE GEORGE , NIKONOV STANISLAV
Published: July 2022

The crystal structure of ribosomal protein L5 from Thermus
thermophilus complexed with a 34-nt fragment comprising
helix III and loop C of Escherichia coli 5S rRNA
has been determined at 2.5 Å resolution. The protein specifically interacts
with the bulged nucleotides at the top of loop C of 5S rRNA. The rRNA and
protein contact surfaces are strongly stabilized by intramolecular
interactions. Charged and polar atoms forming the network of conserved
intermolecular hydrogen bonds are located in two narrow planar parallel
layers belonging to the protein and rRNA, respectively. The regions,
including these atoms conserved in Bacteria and Archaea, can be considered
an RNA–protein recognition module. Comparison of the T.
thermophilus L5 structure in the RNA-bound form with the
isolated Bacillus stearothermophilus L5 structure
shows that the RNA-recognition module on the protein surface does not
undergo significant changes upon RNA binding. In the crystal of the complex,
the protein interacts with another RNA molecule in the asymmetric unit
through the β-sheet concave surface. This protein/RNA interface simulates
the interaction of L5 with 23S rRNA observed in the Haloarcula
marismortui 50S ribosomal subunit.
Delirium in oncological palliative care and clinical cardiology units: A comparative analysis
Authors: Grisales Elisa Sánchez , Higuita Ana María , Correa Marcela Escobar , Gómez John Jairo Vargas , González Carolina Palacio , Daveloza Alicia Krikorian , Vásquez José Gabriel Franco
Published: July 2022

Objective

The aim of this study was to compare the sociodemographic and clinical characteristics of delirium in patients treated in a clinical cardiology unit (CCU) and an oncological palliative care unit (OPCU) at a high-complexity institution.

Context

Delirium is a neuropsychiatric syndrome with multicausal etiology, associated with increased morbidity and mortality.

Method

This was a cross-sectional, analytical observational study. CCU and OPCU patients were evaluated for 480 days. The diagnosis was made according to DSM-V. Sociodemographic characteristics, the Karnofsky index, and the Charlson index were evaluated. Possible etiologies were verified. Severity was assessed with the Delirium Severity Scale (DRS-R98).

Results

A total of 1,986 patients were evaluated, 205 were eligible, and 110 were included in the study (CCU: 61, OPCU: 49). Delirium prevalence was 11.35% in the CCU and 9.87% in the OPCU. CCU patients were 12 years older (p < 0.03) and a history of dementia (41 vs. 8.2%; p < 0.001). Organ failure was the most frequent etiology of delirium in the CCU (41.0%), and in the OPCU, the etiologies were neoplasms (28.6%), side effect of medication (22.4%), and infections (2.5%). Differences were found in the clinical characteristics of delirium evaluated by DRS-R98, with the condition being more severe and with a higher frequency of psychotic symptoms in OPCU patients.

Conclusion

Delirium was a common condition in hospitalized patients in the CCU and the OPCU. The clinical characteristics were similar in both groups; however, significant differences were found in OPCU patients in terms of age, personal history of dementia, and opioid use, as well as the severity of delirium and a greater association with psychotic symptoms. These findings have implications for the early implementation of diagnostic and therapeutic strategies.
Contact with psychiatric care prior to suicide: are there differences between migrants and the majority population in Sweden? A cohort study of 12 474 persons who died by suicide between 2006 and 2016
Authors: Jonsson E. , Sjöqvist H. , Sundvall M. , Bäärnhielm S. , Dalman C. , Hollander A.C.
Published: July 2022

Aims

The aim of this study was to determine possible differences in psychiatric care contact and the type of contact in the year prior to suicide by migrant status and region of origin compared to Swedish persons.

Methods

A population-based open cohort design, using linked national registers, to study all individuals aged 20–64 years who died by suicide between 1 January 2006 and 31 December 2016 in Sweden (N = 12 474). The primary exposure was migrant status compared to the Swedish majority population in the following categories: non-refugee migrants, refugee migrants and children of migrants. The secondary exposure was region of origin in seven regions: Sweden, other Nordic countries, Europe, Sub-Saharan Africa, the Middle East and North Africa, Asia, the Americas and Oceania. The four outcomes were psychiatric in- and outpatient care, prescribed and purchased psychotropic medication and a variable composing the other variables, all measured the year before death. Logistic regression models adjusted for age, sex, income and marital status estimated the likelihood of psychiatric care utilisation by type of care within the year prior to death by migrant status and region of origin (individually and combined).

Results

Out of all who had died by suicide, 81% had had psychiatric care of any type in the year before death by suicide. Among refugees the prevalence of psychiatric care before death by suicide was 88%. Compared with the Swedish reference group, non-refugees and persons from Asia and Sub-Saharan Africa had a lower likelihood of utilising psychiatric care prior to suicide driven by a lower use of prescribed psychotropic medication. Persons from the Middle East and North Africa had a higher likelihood, driven by higher use of psychiatric outpatient care and prescribed psychotropic medication. Non-refugees' likelihood of utilising care before death by suicide was lower within the first 5 years of living in Sweden.

Conclusion

A large share of those who die by suicide use psychiatric care the year before they die. Non-refugee migrants and persons from Asia and Sub-Saharan Africa have a lower likelihood of utilising psychiatric care prior to suicide compared to Swedish, whereas persons from the Middle East and North Africa have a higher likelihood. Health care and policy makers should consider both migrant status, region of origin and time in the new country for further suicide prevention efforts.
Semantic Spaces Are Not Created Equal – How Should We Weigh Them in the Sequel?
Authors: Forthmann Boris , Beaty Roger E. , Johnson Dan R.
Published: July 2022

Abstract: Semantic distance scoring provides an attractive alternative to other scoring approaches for responses in creative thinking tasks. In addition, evidence in support of semantic distance scoring has increased over the last few years. In one recent approach, it has been proposed to combine multiple semantic spaces to better balance the idiosyncratic influences of each space. Thereby, final semantic distance scores for each response are represented by a composite or factor score. However, semantic spaces are not necessarily equally weighted in mean scores, and the usage of factor scores requires high levels of factor determinacy (i.e., the correlation between estimates and true factor scores). Hence, in this work, we examined the weighting underlying mean scores, mean scores of standardized variables, factor loadings, weights that maximize reliability, and equally effective weights on common verbal creative thinking tasks. Both empirical and simulated factor determinacy, as well as Gilmer-Feldt’s composite reliability, were mostly good to excellent (i.e., > .80) across two task types (Alternate Uses and Creative Word Association), eight samples of data, and all weighting approaches. Person-level validity findings were further highly comparable across weighting approaches. Observed nuances and challenges of different weightings and the question of using composites vs. factor scores are thoroughly provided.
Paladin, overexpressed in colon cancer, is required for actin polymerisation and liver metastasis dissemination
Authors: Rademaker Gilles , Costanza Brunella , Pyr dit Ruys Sébastien , Peiffer Raphaël , Agirman Ferman , Maloujahmoum Naïma , Vertommen Didier , Turtoi Andrei , Bellahcène Akeila , Castronovo Vincent , Peulen Olivier
Published: July 2022

Introduction

Colorectal cancer remains a public health issue and most colon cancer patients succumb to the development of metastases. Using a specific protocol of pressure-assisted interstitial fluid extrusion to recover soluble biomarkers, we identified paladin as a potential colon cancer liver metastases biomarker.

Methods

Using shRNA gene knockdown, we explored the biological function of paladin in colon cancer cells and investigated the phospho-proteome within colon cancer cells. We successively applied in vitro migration assays, in vivo metastasis models and co-immunoprecipitation experiments.

Results

We discovered that paladin is required for colon cancer cell migration and metastasis, and that paladin depletion altered the phospho-proteome within colon cancer cells. Data are available via ProteomeXchange with identifier PXD030803. Thanks to immunoprecipitation experiments, we demonstrated that paladin, was interacting with SSH1, a phosphatase involved in colon cancer metastasis. Finally, we showed that paladin depletion in cancer cells results in a less dynamic actin cytoskeleton.

Conclusions

Paladin is an undervalued protein in oncology. This study highlights for the first time that, paladin is participating in actin cytoskeleton remodelling and is required for efficient cancer cell migration.
Cross-reactivity of eight SARS-CoV-2 variants rationally predicts immunogenicity clustering in sarbecoviruses
Authors: Li Qianqian , Zhang Li , Liang Ziteng , Wang Nan , Liu Shuo , Li Tao , Yu Yuanling , Cui Qianqian , Wu Xi , Nie Jianhui , Wu Jiajing , Cui Zhimin , Lu Qiong , Wang Xiangxi , Huang Weijin , Wang Youchun
Published: July 2022

A steep rise in Omicron reinfection cases suggests that this variant has increased immune evasion ability. To evaluate its antigenicity relationship with other variants, antisera from guinea pigs immunized with spike protein of SARS-CoV-2 variants of concern (VOCs) and variants of interest (VOIs) were cross-tested against pseudotyped variants. The neutralization activity against Omicron was markedly reduced when other VOCs or VOIs were used as immunogens, and Omicron (BA.1)-elicited sera did not efficiently neutralize the other variants. However, a Beta or Omicron booster, when administered as the 4th dose 3-months after the 3rd dose of any of the variants, could elicit broad neutralizing antibodies against all of the current variants including Omicron BA.1. Further analysis with 280 available antigen–antibody structures and quantification of immune escape from 715 reported neutralizing antibodies provide explanations for the observed differential immunogenicity. Three distinct clades predicted using an in silico algorithm for clustering of sarbecoviruses based on immune escape provide key information for rational design of vaccines.
Amino acid utilization allows intestinal dominance ofLactobacillus amylovorus
Authors: Jing Yujia , Mu Chunlong , Wang Huisong , Shen Junhua , Zoetendal Erwin G , Zhu Weiyun
Published: July 2022

The mammalian intestine harbors heterogeneous distribution of microbes among which specific taxa (e.g. Lactobacillus) dominate across mammals. Deterministic factors such as nutrient availability and utilization may affect microbial distributions. Due to physiological complexity, mechanisms linking nutrient utilization and the dominance of key taxa remain unclear. Lactobacillus amylovorus is a predominant species in the small intestine of pigs. Employing a pig model, we found that the small intestine was dominated by Lactobacillus and particularly L. amylovorus, and enriched with peptide-bound amino acids (PBAAs), all of which were further boosted after a peptide-rich diet. To investigate the bacterial growth dominance mechanism, a representative strain L. amylovorus S1 was isolated from the small intestine and anaerobically cultured in media with free amino acids or peptides as sole nitrogen sources. L. amylovorus S1 grew preferentially with peptide-rich rather than amino acid-rich substrates, as reflected by enhanced growth and PBAA utilization, and peptide transporter upregulations. Utilization of free amino acids (e.g. methionine, valine, lysine) and expressions of transporters and metabolic enzymes were enhanced simultaneously in peptide-rich substrate. Additionally, lactate was elevated in peptide-rich substrates while acetate in amino acid-rich substrates, indicating distinct metabolic patterns depending on substrate forms. These results suggest that an increased capability of utilizing PBAAs contributes to the dominance of L. amylovorus, indicating amino acid utilization as a deterministic factor affecting intestinal microbial distribution. These findings may provide new insights into the microbe-gut nutrition interplay and guidelines for dietary manipulations toward gut health especially small intestine health.
ARHGEF2/EDN1 pathway participates in ER stress-related drug resistance of hepatocellular carcinoma by promoting angiogenesis and malignant proliferation
Authors: Zhu Yue , Liu Weiwei , Wang Zishu , Wang Yanfei , Tan Chaisheng , Pan Zhipeng , Wang Anqi , Liu Jiatao , Sun Guoping
Published: July 2022

Endoplasmic reticulum (ER) stress is widely involved in the drug resistance of hepatocellular carcinoma (HCC), but the mechanism of ER stress-induced drug resistance involves multiple signaling pathways that cannot be fully explained. Exploring genes associated with ER stress could yield a novel therapeutic target for ER stress-induced drug resistance. By analyzing RNA-sequencing, ATAC-sequencing, and Chip-sequencing data of Tunicamycin (TM)-treated or untreated HCC cells, we found that Rho guanine nucleotide exchange factor 2 (ARHGEF2) is upregulated in HCC cells with ER stress. ARHGEF2 plays an active role in tumor malignant progression. Notwithstanding, no research has been done on the link between ER stress and ARHGEF2. The function of ARHGEF2 as a novel downstream effector of ER stress in the angiogenesis and treatment resistance of HCC was revealed in this work. ARHGEF2 overexpression was linked to malignant development and a poor prognosis in HCC. ER stress stimulates the expression of ARHGEF2 through upregulation of ZNF263. Elevated ARHGEF2 accelerates HCC angiogenesis via the EDN1 pathway, enhances HCC cell proliferation and tumor growth both in vitro and in vivo, and contributes to ER stress-related treatment resistance. HCC cell growth was more inhibited when ARHGEF2 knockdown was paired with targeted medicines. Collectively, we uncovered a previously hidden mechanism where ARHGEF2/EDN1 pathway promotes angiogenesis and participates in ER stress-related drug resistance in HCC.
Emerging mechanisms of pyroptosis and its therapeutic strategy in cancer
Authors: Lu Liqing , Zhang Ye , Tan Xuemei , Merkher Yulia , Leonov Sergey , Zhu Li , Deng Yalan , zhang Huajun , Zhu Dandan , Tan Yuying , Fu Ying , Liu Ting , Chen Yongheng
Published: July 2022

Pyroptosis, a type of inflammatory programmed cell death, is triggered by caspase cleavage of gasdermin family proteins. Based on accumulating evidence, pyroptosis is closely associated with tumour development, but the molecular mechanism underlying pyroptosis activation and the signalling pathways regulated by pyroptosis remain unclear. In this review, we first briefly introduce the definition, morphological characteristics, and activation pathways of pyroptosis and the effect of pyroptosis on anticancer immunity. Then we review recent progress concerning the complex role of pyroptosis in various tumours. Importantly, we summarise various FDA-approved chemotherapy drugs or natural compounds that exerted antitumor properties by inducing pyroptosis of cancer cells. Moreover, we also focus on the current application of nanotechnology-induced pyroptosis in tumour therapy. In addition, some unsolved problems and potential future research directions are also raised.
Competing paradigms of obesity pathogenesis: energy balance versus carbohydrate-insulin models
Authors: Ludwig David S. , Apovian Caroline M. , Aronne Louis J. , Astrup Arne , Cantley Lewis C. , Ebbeling Cara B. , Heymsfield Steven B. , Johnson James D. , King Janet C. , Krauss Ronald M. , Taubes Gary , Volek Jeff S. , Westman Eric C. , Willett Walter C. , Yancy William S. , Friedman Mark I.
Published: July 2022

The obesity pandemic continues unabated despite a persistent public health campaign to decrease energy intake (“eat less”) and increase energy expenditure (“move more”). One explanation for this failure is that the current approach, based on the notion of energy balance, has not been adequately embraced by the public. Another possibility is that this approach rests on an erroneous paradigm. A new formulation of the energy balance model (EBM), like prior versions, considers overeating (energy intake > expenditure) the primary cause of obesity, incorporating an emphasis on “complex endocrine, metabolic, and nervous system signals” that control food intake below conscious level. This model attributes rising obesity prevalence to inexpensive, convenient, energy-dense, “ultra-processed” foods high in fat and sugar. An alternative view, the carbohydrate-insulin model (CIM), proposes that hormonal responses to highly processed carbohydrates shift energy partitioning toward deposition in adipose tissue, leaving fewer calories available for the body’s metabolic needs. Thus, increasing adiposity causes overeating to compensate for the sequestered calories. Here, we highlight robust contrasts in how the EBM and CIM view obesity pathophysiology and consider deficiencies in the EBM that impede paradigm testing and refinement. Rectifying these deficiencies should assume priority, as a constructive paradigm clash is needed to resolve long-standing scientific controversies and inform the design of new models to guide prevention and treatment. Nevertheless, public health action need not await resolution of this debate, as both models target processed carbohydrates as major drivers of obesity.
Win-win opportunities combining high yields with high multi-taxa biodiversity in tropical agroforestry
Authors: Wurz Annemarie , Tscharntke Teja , Martin Dominic Andreas , Osen Kristina , Rakotomalala Anjaharinony A. N. A. , Raveloaritiana Estelle , Andrianisaina Fanilo , Dröge Saskia , Fulgence Thio Rosin , Soazafy Marie Rolande , Andriafanomezantsoa Rouvah , Andrianarimisa Aristide , Babarezoto Fenohaja Soavita , Barkmann Jan , Hänke Hendrik , Hölscher Dirk , Kreft Holger , Rakouth Bakolimalala , Guerrero-Ramírez Nathaly R. , Ranarijaona Hery Lisy Tiana , Randriamanantena Romual , Ratsoavina Fanomezana Mihaja , Raveloson Ravaomanarivo Lala Harivelo , Grass Ingo
Published: July 2022

Resolving ecological-economic trade-offs between biodiversity and yields is a key challenge when addressing the biodiversity crisis in tropical agricultural landscapes. Here, we focused on the relation between seven different taxa (trees, herbaceous plants, birds, amphibians, reptiles, butterflies, and ants) and yields in vanilla agroforests in Madagascar. Agroforests established in forests supported overall 23% fewer species and 47% fewer endemic species than old-growth forests, and 14% fewer endemic species than forest fragments. In contrast, agroforests established on fallows had overall 12% more species and 38% more endemic species than fallows. While yields increased with vanilla vine density and length, non-yield related variables largely determined biodiversity. Nonetheless, trade-offs existed between yields and butterflies as well as  reptiles. Vanilla yields were generally unrelated to richness of trees, herbaceous plants, birds, amphibians, reptiles, and ants, opening up possibilities for conservation outside of protected areas and restoring degraded land to benefit farmers and biodiversity alike.
Overload wave-memory induces amnesia of a self-propelled particle
Authors: Hubert Maxime , Perrard Stéphane , Vandewalle Nicolas , Labousse Matthieu
Published: July 2022

Information storage is a key element of autonomous, out-of-equilibrium dynamics, especially for biological and synthetic active matter. In synthetic active matter however, the implementation of internal memory in self-propelled systems is often absent, limiting our understanding of memory-driven dynamics. Recently, a system comprised of a droplet generating its guiding wavefield appeared as a prime candidate for such investigations. Indeed, the wavefield, propelling the droplet, encodes information about the droplet trajectory and the amount of information can be controlled by a single scalar experimental parameter. In this work, we show numerically and experimentally that the accumulation of information in the wavefield induces the loss of time correlations, where the dynamics can then be described by a memory-less process. We rationalize the resulting statistical behavior by defining an effective temperature for the particle dynamics where the wavefield acts as a thermostat of large dimensions, and by evidencing a minimization principle of the generated wavefield.
Reduction of primary graft dysfunction using cytokine adsorption during organ preservation and after lung transplantation
Authors: Ghaidan Haider , Stenlo Martin , Niroomand Anna , Mittendorfer Margareta , Hirdman Gabriel , Gvazava Nika , Edström Dag , Silva Iran A. N. , Broberg Ellen , Hallgren Oskar , Olm Franziska , Wagner Darcy E. , Pierre Leif , Hyllén Snejana , Lindstedt Sandra
Published: July 2022

Despite improvements, lung transplantation remains hampered by both a scarcity of donor organs and by mortality following primary graft dysfunction (PGD). Since acute respiratory distress syndrome (ARDS) limits donor lungs utilization, we investigated cytokine adsorption as a means of treating ARDS donor lungs. We induced mild to moderate ARDS using lipopolysaccharide in 16 donor pigs. Lungs were then treated with or without cytokine adsorption during ex vivo lung perfusion (EVLP) and/or post-transplantation using extracorporeal hemoperfusion. The treatment significantly decreased cytokine levels during EVLP and decreased levels of immune cells post-transplantation. Histology demonstrated fewer signs of lung injury across both treatment periods and the incidence of PGD was significantly reduced among treated animals. Overall, cytokine adsorption was able to restore lung function and reduce PGD in lung transplantation. We suggest this treatment will increase the availability of donor lungs and increase the tolerability of donor lungs in the recipient.
Dirac-source diode with sub-unity ideality factor
Authors: Myeong Gyuho , Shin Wongil , Sung Kyunghwan , Kim Seungho , Lim Hongsik , Kim Boram , Jin Taehyeok , Park Jihoon , Lee Taehun , Fuhrer Michael S. , Watanabe Kenji , Taniguchi Takashi , Liu Fei , Cho Sungjae
Published: July 2022

An increase in power consumption necessitates a low-power circuit technology to extend Moore’s law. Low-power transistors, such as tunnel field-effect transistors (TFETs), negative-capacitance field-effect transistors (NC-FETs), and Dirac-source field-effect transistors (DS-FETs), have been realised to break the thermionic limit of the subthreshold swing (SS). However, a low-power rectifier, able to overcome the thermionic limit of an ideality factor (η) of 1 at room temperature, has not been proposed yet. In this study, we have realised a DS diode based on graphene/MoS2/graphite van der Waals heterostructures, which exhibits a steep-slope characteristic curve, by exploiting the linear density of states (DOSs) of graphene. For the developed DS diode, we obtained η < 1 for more than four decades of drain current (ηave_4dec < 1) with a minimum value of 0.8, and a rectifying ratio exceeding 108. The realisation of a DS diode represents an additional step towards the development of low-power electronic circuits.
Tracing the origin of lithium in Li-ion batteries using lithium isotopes
Authors: Desaulty Anne-Marie , Monfort Climent Daniel , Lefebvre Gaétan , Cristiano-Tassi Antonella , Peralta David , Perret Sébastien , Urban Anthony , Guerrot Catherine
Published: July 2022

Rechargeable lithium-ion batteries (LIB) play a key role in the energy transition towards clean energy, powering electric vehicles, storing energy on renewable grids, and helping to cut emissions from transportation and energy sectors. Lithium (Li) demand is estimated to increase considerably in the near future, due to the growing need for clean-energy technologies. The corollary is that consumer expectations will also grow in terms of guarantees on the origin of Li and the efforts made to reduce the environmental and social impact potentially associated with its extraction. Today, the LIB-industry supply chain is very complex, making it difficult for end users to ensure that Li comes from environmentally and responsible sources. Using an innovative geochemical approach based on the analysis of Li isotopes of raw and processed materials, we show that Li isotope ‘fingerprints’ are a useful tool for determining the origin of lithium in LIB. This sets the stage for a new method ensuring the certification of Li in LIB.
Differential neutralization and inhibition of SARS-CoV-2 variants by antibodies elicited by COVID-19 mRNA vaccines
Authors: Wang Li , Kainulainen Markus H. , Jiang Nannan , Di Han , Bonenfant Gaston , Mills Lisa , Currier Michael , Shrivastava-Ranjan Punya , Calderon Brenda M. , Sheth Mili , Mann Brian R. , Hossain Jaber , Lin Xudong , Lester Sandra , Pusch Elizabeth A. , Jones Joyce , Cui Dan , Chatterjee Payel , Jenks M. Harley , Morantz Esther K. , Larson Gloria P. , Hatta Masato , Harcourt Jennifer L. , Tamin Azaibi , Li Yan , Tao Ying , Zhao Kun , Lacek Kristine , Burroughs Ashley , Wang Wei , Wilson Malania , Wong Terianne , Park So Hee , Tong Suxiang , Barnes John R. , Tenforde Mark W. , Self Wesley H. , Shapiro Nathan I. , Exline Matthew C. , Files D. Clark , Gibbs Kevin W. , Hager David N. , Patel Manish , Halpin Alison L. , McMullan Laura K. , Lee Justin S. , Xia Hongjie , Xie Xuping , Shi Pei-Yong , Davis C. Todd , Spiropoulou Christina F. , Thornburg Natalie J. , Oberste M. Steven , Dugan Vivien G. ,   SSEV Bioinformatics Working Group, Batra Dhwani , Beck Andrew S. , Caravas Jason , Chau Reina , Cintron-Moret Roxana , Cook Peter W. , Gerhart Jonathan , Gulvik Christopher A. , Hassell Norman , Howard Dakota , Knipe Kristen , Kondor Rebecca J. , Kovacs Nicholas A. , Moser Kara , Reddy-Nagilla Roopa , Paden Clinton R. , Rambo-Martin Benjamin , Mathew Sandra , Schmerer Matthew W. , Shepard Samuel S. , Shirk Philip , Stanton Richard A. , Stark Thomas J. , Sula Erisa , Tymeckia Kendall , Unoarumhi Yvette , Subbalakshmi Voleti , Zheng Xiao-yu , Wentworth David E. , Zhou Bin
Published: July 2022

The evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in the emergence of new variant lineages that have exacerbated the COVID-19 pandemic. Some of those variants were designated as variants of concern/interest (VOC/VOI) by national or international authorities based on many factors including their potential impact on vaccine-mediated protection from disease. To ascertain and rank the risk of VOCs and VOIs, we analyze the ability of 14 variants (614G, Alpha, Beta, Gamma, Delta, Epsilon, Zeta, Eta, Theta, Iota, Kappa, Lambda, Mu, and Omicron) to escape from mRNA vaccine-induced antibodies. The variants show differential reductions in neutralization and replication by post-vaccination sera. Although the Omicron variant (BA.1, BA.1.1, and BA.2) shows the most escape from neutralization, sera collected after a third dose of vaccine (booster sera) retain moderate neutralizing activity against that variant. Therefore, vaccination remains an effective strategy during the COVID-19 pandemic.
Targeting de novo lipogenesis and the Lands cycle induces ferroptosis in KRAS-mutant lung cancer
Authors: Bartolacci Caterina , Andreani Cristina , Vale Gonçalo , Berto Stefano , Melegari Margherita , Crouch Anna Colleen , Baluya Dodge L. , Kemble George , Hodges Kurt , Starrett Jacqueline , Politi Katerina , Starnes Sandra L. , Lorenzini Daniele , Raso Maria Gabriela , Solis Soto Luisa M. , Behrens Carmen , Kadara Humam , Gao Boning , Wistuba Ignacio I. , Minna John D. , McDonald Jeffrey G. , Scaglioni Pier Paolo
Published: July 2022

Mutant KRAS (KM), the most common oncogene in lung cancer (LC), regulates fatty acid (FA) metabolism. However, the role of FA in LC tumorigenesis is still not sufficiently characterized. Here, we show that KMLC has a specific lipid profile, with high triacylglycerides and phosphatidylcholines (PC). We demonstrate that FASN, the rate-limiting enzyme in FA synthesis, while being dispensable in EGFR-mutant or wild-type KRAS LC, is required for the viability of KMLC cells. Integrating lipidomic, transcriptomic and functional analyses, we demonstrate that FASN provides saturated and monounsaturated FA to the Lands cycle, the process remodeling oxidized phospholipids, such as PC. Accordingly, blocking either FASN or the Lands cycle in KMLC, promotes ferroptosis, a reactive oxygen species (ROS)- and iron-dependent cell death, characterized by the intracellular accumulation of oxidation-prone PC. Our work indicates that KM dictates a dependency on newly synthesized FA to escape ferroptosis, establishing a targetable vulnerability in KMLC.
Thermodynamics-guided alloy and process design for additive manufacturing
Authors: Sun Zhongji , Ma Yan , Ponge Dirk , Zaefferer Stefan , Jägle Eric A. , Gault Baptiste , Rollett Anthony D. , Raabe Dierk
Published: July 2022

In conventional processing, metals go through multiple manufacturing steps including casting, plastic deformation, and heat treatment to achieve the desired property. In additive manufacturing (AM) the same target must be reached in one fabrication process, involving solidification and cyclic remelting. The thermodynamic and kinetic differences between the solid and liquid phases lead to constitutional undercooling, local variations in the solidification interval, and unexpected precipitation of secondary phases. These features may cause many undesired defects, one of which is the so-called hot cracking. The response of the thermodynamic and kinetic nature of these phenomena to high cooling rates provides access to the knowledge-based and tailored design of alloys for AM. Here, we illustrate such an approach by solving the hot cracking problem, using the commercially important IN738LC superalloy as a model material. The same approach could also be applied to adapt other hot-cracking susceptible alloy systems for AM.
ProtGPT2 is a deep unsupervised language model for protein design
Authors: Ferruz Noelia , Schmidt Steffen , Höcker Birte
Published: July 2022

Protein design aims to build novel proteins customized for specific purposes, thereby holding the potential to tackle many environmental and biomedical problems. Recent progress in Transformer-based architectures has enabled the implementation of language models capable of generating text with human-like capabilities. Here, motivated by this success, we describe ProtGPT2, a language model trained on the protein space that generates de novo protein sequences following the principles of natural ones. The generated proteins display natural amino acid propensities, while disorder predictions indicate that 88% of ProtGPT2-generated proteins are globular, in line with natural sequences. Sensitive sequence searches in protein databases show that ProtGPT2 sequences are distantly related to natural ones, and similarity networks further demonstrate that ProtGPT2 is sampling unexplored regions of protein space. AlphaFold prediction of ProtGPT2-sequences yields well-folded non-idealized structures with embodiments and large loops and reveals topologies not captured in current structure databases. ProtGPT2 generates sequences in a matter of seconds and is freely available.
Actin nano-architecture of phagocytic podosomes
Authors: Herron J. Cody , Hu Shiqiong , Watanabe Takashi , Nogueira Ana T. , Liu Bei , Kern Megan E. , Aaron Jesse , Taylor Aaron , Pablo Michael , Chew Teng-Leong , Elston Timothy C. , Hahn Klaus M.
Published: July 2022

Podosomes are actin-enriched adhesion structures important for multiple cellular processes, including migration, bone remodeling, and phagocytosis. Here, we characterize the structure and organization of phagocytic podosomes using interferometric photoactivated localization microscopy, a super-resolution microscopy technique capable of 15–20 nm resolution, together with structured illumination microscopy and localization-based super-resolution microscopy. Phagocytic podosomes are observed during frustrated phagocytosis, a model in which cells attempt to engulf micropatterned IgG antibodies. For circular patterns, this results in regular arrays of podosomes with well-defined geometry. Using persistent homology, we develop a pipeline for semi-automatic identification and measurement of podosome features. These studies reveal an hourglass shape of the podosome actin core, a protruding knob at the bottom of the core, and two actin networks extending from the core. Additionally, the distributions of paxillin, talin, myosin II, α-actinin, cortactin, and microtubules relative to actin are characterized.