bluuebunny/crossref_metadata_2025 huggingface dataset:
Switch to checkpoint inhibition after targeted therapy at time of progression or during ongoing response: A retrospective single‐centre experience in patients with BRAF‐mutated melanoma
Authors: Reijers Irene L. M. , Rozeman Elisa A. , Wilgenhof Sofie , van Thienen Johannes V. , Haanen John B. A. G. , Blank Christian U.
Published: October 2019

BRAF + MEK inhibition is preferentially applied as first‐line therapy in BRAF V600‐mutated melanoma patients with unfavourable prognostic features, due to the ability of targeted therapy (TT) to induce rapid symptom control, decrease tumour burden and normalize lactate dehydrogenase (LDH) levels. In addition, short‐term TT transiently increases tumour antigen presentation and tumour influx of T cells. Therefore, it might be favourable to switch TT to checkpoint inhibition (CPI) before progression (PD). We retrospectively analysed melanoma patients treated first line with TT (TT1) and who subsequently switched to CPI during response to TT (sDR group) or at progression upon TT (sPD group). We identified 74 patients (n = 37 sDR group and n = 37 sPD group). ORR to CPI was 27.0% in the sDR group versus 24.3% in the sPD group (p = .790). Median was PFS 2.5 months versus 1.2 months (p = .145), and median OS was 30.6 versus 14.1 months (p = .007). After adjusting for baseline differences and known prognostic factors, hazard ratios (HRs) favouring sDR were 0.89 for PFS upon CPI (p = .956) and 0.48 for OS (p = .055). Thus, patients switching to CPI during ongoing clinical benefit from TT do not have an inferior outcome. Due to baseline imbalances and small patient population, a favourable trend for the sDR group can be hypothesized only.
Predicting the potential distribution of Pseudomonas syringae pv. actinidiae in China using ensemble models
Authors: Qin Z. , Zhang J. E. , Jiang Y. P. , Wang R. L. , Wu R. S.
Published: October 2019

Pseudomonas syringae pv. actinidiae (Psa) is a causal agent of kiwifruit bacterial canker worldwide, which has affected kiwifruit vines in China since 1996 and has subsequently spread to the main cultivation areas. Based on occurrence of Psa and pseudo‐absences randomly generated in China, the consensus‐based modelling technique was used to estimate the spatial spread of Psa epidemics within China. Environmental variables that related to Psa development were identified, and their contributions to Psa development were evaluated. Three modelling algorithms, namely generalized boosting models (GBM), random forests (RF) and classification tree analysis (CTA) within the BIOMOD2 framework, were employed to construct the model. The ensemble models weighted by the true skill statistic (TSS) value were used to predict the current habitat suitability of Psa, and were projected using the four general circulation models (GCMs) to assess range shifts under two types of representative concentration pathways (RCP 4.5 and RCP 8.5) by 2050. The results indicated that precipitation in March and mean temperature of warmest quarter were the most important limiting factors for distribution of Psa. The predictive accuracy of the ensemble model showed acceptable predictive powers (TSS = 0.852). Under future climate conditions, substantial net loss of suitability for Psa was estimated to be 3.03–12.5% under RCP 4.5 (except one GCM), and 2.46–9.89% under RCP 8.5. Shrinkage of suitable habitats was detected mainly in the areas currently infected by Psa. Special attention should be given to recent infectious regions in south and southwest China, considering the locally expanding kiwifruit commercial plantations.
Absorbing partner knowledge in R&D collaborations – the influence of founders on potential and realized absorptive capacity
Authors: Mueller Elisabeth , Syme Lorna , Haeussler Carolin
Published: October 2019

We investigate whether founder participation in research and development collaborations enhances the two dimensions of absorptive capacity (ACAP): potential ACAP and realized ACAP. Based on a longitudinal firm‐patent dataset of over 700 collaborations, and using a novel measure of ACAP, we find that founder involvement enhances potential ACAP provided the knowledge bases of focal firm and partner are related. Once knowledge has been absorbed, founder involvement increases realized ACAP irrespective of relatedness. Thus, we highlight the merit of treating the dimensions of ACAP separately by showing differing effects of founder involvement. Our paper emphasizes the outstanding role founders play in the R&D process of their firms. Firms should consider carefully the allocation of team members to R&D projects because team members differ with respect to their ACAP.
Neuroeconomics, health psychology, and the interdisciplinary study of preventative health behavior
Authors: DeStasio Krista L. , Clithero John A. , Berkman Elliot T.
Published: October 2019

The goal of this article is to introduce readers to theories, tools, and evidence from the field of neuroeconomics and to describe how health psychology and neuroeconomics can be mutually informative in the study of preventative health behaviors. Preventative health behavior here refers to both individual actions that impact one's health (e.g., exercise) and broader behavioral patterns, such as those captured in personality constructs. Although neuroeconomic researchers have begun to incorporate health‐relevant behaviors into their studies, the full potential of this research to inform preventative health models is as yet unrealized. What is needed to “translate up” is the unification of rich theoretical content from health psychology with investigations by neuroeconomic researchers of the decision‐making process during health‐relevant choices. We identify choice as a central, shared feature across models of preventative health behavior that can serve as an inroad for neuroeconomics to contribute to existing models and highlight commonalities that might not otherwise be apparent. A central premise of our argument is that, because health decisions are nearly always multiply determined, a more precise and mechanistic understanding of how choices are made is an important but understudied topic in health psychology. A partnership between health psychologists and neuroeconomic researchers can yield valuable insights into how preventative health choice is made and to identify targets and methods for intervention.
Obstacle‐limited service coverage: A new geospatial approach
Authors: Hong Insu , Murray Alan T.
Published: October 2019

Service coverage is a crucial component of spatial decision‐making involving facility siting. Determining coverage requires knowledge about travel behavior and accessibility across a region, as well as supporting methods of measurement and derivation when actual travel cannot necessarily be observed. When service is provided using vehicles that move freely without the restriction posed by roads (e.g., airplanes, helicopters, unmanned aerial vehicles/drones, boats, ships, and submarines), straight‐line travel is regularly assumed. However, this common assumption is often violated by geographical obstructions, resulting in overestimated service coverage. To date, no methods have been developed capable of accounting for obstacle‐limited service coverage. Existing methods either completely ignore obstructions or crudely estimate impacts on travel. In this research, we develop a novel method, ESP‐Cover, capable of deriving accurate obstacle‐limited coverage without introducing representation errors. A location siting problem involving drone‐based package delivery is presented to highlight the necessity of explicitly accounting for obstacles in system design. The assessment results demonstrate the importance of accurate derivation of the obstacle‐limited coverage for spatial decision‐making and the accuracy of the ESP‐Cover method in coverage derivation.
Atopic dermatitis in West Highland white terriers – part I: natural history of atopic dermatitis in the first three years of life
Authors: Favrot Claude , Fischer Nina , Olivry Thierry , Zwickl Lena , Audergon Sabrina , Rostaher Ana
Published: October 2019

Background

Canine atopic dermatitis (cAD) is a common allergic skin disease that is known to affect individuals early in life; the natural history of its initial development has not been documented. Some breeds such as West Highland white terriers (WHWTs) are highly predisposed to cAD.

Objectives

To follow 100 WHWT puppies during their first three years and to record the onset of clinical signs of cAD.

Animals

One hundred and eight puppies from 29 litters were included and 90 were followed for three years.

Methods and materials

Puppies were examined initially while with their breeders. After adoption, the owners were contacted twice each year and dogs were examined by veterinarians if signs compatible with cAD were detected; diagnosis of cAD was by two different definitions. The onset, location of the clinical signs and severity of cAD, as well as co‐morbidities were recorded.

Results

The prevalence of cAD in the cohort was 52%. Most affected dogs (60%) developed signs of cAD during their first year of life and males were over‐represented. The location of clinical signs mirrored those of previous descriptions. The severity of cAD was mild in 36% and severe in 13% of affected WHWTs. Dogs with cAD often exhibited other atopic diseases, but only gastro‐intestinal signs were significantly different between WHWTs with and without cAD. Adverse reaction to foods was diagnosed in 24% of dogs.

Conclusion and clinical importance

This longitudinal study of puppies from a predisposed breed sheds new light on the early development of cAD in WHWTs.
Progress in the synthesis of Al- and Cr-based sesquioxide coatings for protective applications
Authors: Koller Christian Martin , Stueber Michael , Mayrhofer Paul-Heinz
Published: October 2019

The challenge of synthesizing protective alumina coatings in corundum structure at moderate temperatures inspired the development of novel strategies of both thin film processing and microstructural thin film design. While the growth of pure corundum coatings is still a domain of chemical vapor deposition, new concepts developed in physical vapor deposition addressed the growth of advanced solid solutions, nanocomposites, or multilayers. The system Al-Cr-O has received huge attention as thin films of the type (Al1−xCrx)2O3 could be grown at substrate temperatures even below 500 °C in laboratory model experiments. These coatings offer particular potential for applications that require chemical inertness, thermal stability, mechanical strength, and excellent tribological properties at elevated temperatures. Mastering its low temperature deposition is one of the major aims of industrial research, as it would also enable the protection of temperature-sensitive components and consequently path the way for novel, yet not realizable applications. This work summarizes the state of the art and recent progress in the development and synthesis of such sesquioxide protective coatings prepared by physical vapor deposition. General coherencies are described for (Al1−XCrx)2O3 coatings. Topics covered are important growth parameters (i.e., the oxygen gas flow and the substrate bias), the chemical composition and its impact on alloying concepts applicable to (Al1−xCrx)2O3 coatings, specific architectural coating designs, and relevant properties such as the thermal stability and material response upon annealing in oxidative environments. In addition, a brief outlook into the development of other Cr-based sesquioxide thin films, (Cr,Zr)2O3 and (Cr,V)2O3, is given.
Acoustic end corrections for micro-perforated plates
Authors: Naderyan Vahid , Raspet Richard , Hickey Craig J. , Mohammadi Mohammad
Published: October 2019

Micro-perforated plates (MPPs) are acoustically important elements in micro-electro-mechanical systems (MEMS). In this work an analytical solution for perforated plates is combined with finite element method (FEM) to develop formulas for the reactive and resistive end effects of the perforations on the plate. The reactive end effect is found to depend on the hole radius and porosity. The resistive end effect is found to depend on hole radius only. FEM is also used to develop an understanding of the loss mechanism that corresponds to the resistive end effects. The developed models can be used in optimization studies of the MEMS and MPPs.
Obscure Cold War nerve agents set to be banned
Authors: Stone Richard
Published: October 2019

"Novichoks," used in 2018 attack on former spy, to come under chemical weapons treaty.
The coming electric vehicle transformation
Authors: Crabtree George
Published: October 2019

A future electric transportation market will depend on battery innovation
MAIT cells are imprinted by the microbiota in early life and promote tissue repair
Authors: Constantinides Michael G. , Link Verena M. , Tamoutounour Samira , Wong Andrea C. , Perez-Chaparro P. Juliana , Han Seong-Ji , Chen Y. Erin , Li Kelin , Farhat Sepideh , Weckel Antonin , Krishnamurthy Siddharth R. , Vujkovic-Cvijin Ivan , Linehan Jonathan L. , Bouladoux Nicolas , Merrill E. Dean , Roy Sobhan , Cua Daniel J. , Adams Erin J. , Bhandoola Avinash , Scharschmidt Tiffany C. , Aubé Jeffrey , Fischbach Michael A. , Belkaid Yasmine
Published: October 2019

Commensals rule the MAITrix

Mucosal-associated invariant T (MAIT) cells play an important role in mucosal homeostasis. MAIT cells recognize microbial small molecules presented by the major histocompatibility complex class Ib molecule MR1. MAIT cells are absent in germ-free mice, and the mechanisms by which microbiota control MAIT cell development are unknown (see the Perspective by Oh and Unutmaz). Legoux
et al.
show that, in mice, development of MAIT cells within the thymus is governed by the bacterial product 5-(2-oxopropylideneamino)-6-
d
-ribitylaminouracil, which rapidly traffics from the mucosa to the thymus, where it is captured by MR1 and presented to developing MAIT cells. Constantinides
et al.
report that MAIT cell induction only occurs during a limited, early-life window and requires exposure to defined microbes that produce riboflavin derivatives. Continual interactions between MAIT cells and commensals in the skin modulates tissue repair functions. Together, these papers highlight how the microbiota can direct immune cell development and subsequent function at mucosal sites by secreting compounds that act like self-antigens.

Science
, this issue p.
494
, p.
eaax6624
; see also p.
419
Broadly protective human antibodies that target the active site of influenza virus neuraminidase
Authors: Stadlbauer Daniel , Zhu Xueyong , McMahon Meagan , Turner Jackson S. , Wohlbold Teddy J. , Schmitz Aaron J. , Strohmeier Shirin , Yu Wenli , Nachbagauer Raffael , Mudd Philip A. , Wilson Ian A. , Ellebedy Ali H. , Krammer Florian
Published: October 2019

Alternative influenza target

There is a pressing need for a broadly protective influenza vaccine that can neutralize this constantly varying, deadly virus. Stadlbauer
et al.
turned their attention away from the current vaccine target—the mutable hemagglutinin—and investigated an alternative, less variable virus-coat glycoprotein: neuraminidase. The authors extracted monoclonal antibodies (mAbs) from a human donor naturally infected with the H3N2 virus subtype. In mice, the mAbs were broadly protective against influenza virus A groups 1 and 2 (human, avian, and swine origin) and some influenza B viruses. These mAbs were also therapeutically effective as late as 72 hours after infection. The wide range of reactivity probably relates to the infection history of the donor, whose plasmablasts generated antibodies with long regions that insert into the active site of the neuraminidase enzyme.

Science
, this issue p.
499
Cryo-EM structures of the human cation-chloride cotransporter KCC1
Authors: Liu Si , Chang Shenghai , Han Binming , Xu Lingyi , Zhang Mingfeng , Zhao Cheng , Yang Wei , Wang Feng , Li Jingyuan , Delpire Eric , Ye Sheng , Bai Xiao-chen , Guo Jiangtao
Published: October 2019

Coupled transport

Cation-chloride cotransporters move chloride and cations across the cell membrane and are important in regulating cell volume and setting the chloride concentration inside the cell. Mutations lead to serious diseases, such as epilepsy. Liu
et al.
present the structure of the human potassium-chloride cotransporter KCC1, as determined by cryo–electron microscopy. Based on the structure, functional studies, and molecular dynamics simulations, they propose an ion transport model. The structure provides a framework for interpreting disease-related mutations in potassium-chloride cotransporters.

Science
, this issue p.
505
Dense connectomic reconstruction in layer 4 of the somatosensory cortex
Authors: Motta Alessandro , Berning Manuel , Boergens Kevin M. , Staffler Benedikt , Beining Marcel , Loomba Sahil , Hennig Philipp , Wissler Heiko , Helmstaedter Moritz
Published: October 2019

Brain anatomy revealed in startling detail

The mammalian cerebral cortex is an enormously complex network of neuronal processes that are long and thin, branching, and extremely densely packed. This high packing density has made the reconstruction of cortical neuronal networks challenging. Motta
et al.
used advanced automated imaging and analysis tools to reconstruct with high spatial resolution the morphological features of 89 neurons and their connections in the mouse barrel cortex. The reconstruction covered an area more than two orders of magnitude larger than earlier neuroanatomical mapping attempts. This approach revealed information about the connectivity of inhibitory and excitatory synapses of corticocortical as well as excitatory thalamocortical connections.

Science
, this issue p.
eaay3134
Self-organization of
parS
centromeres by the ParB CTP hydrolase
Authors: Soh Young-Min , Davidson Iain Finley , Zamuner Stefano , Basquin Jérôme , Bock Florian Patrick , Taschner Michael , Veening Jan-Willem , De Los Rios Paolo , Peters Jan-Michael , Gruber Stephan
Published: October 2019

CTP hydrolysis organizes chromosomes

The bacterial DNA
parS
centromere recruits the ParB protein to the bacterial chromosome. Soh
et al.
found that the widespread family of ParB proteins not only bind DNA but also bind and hydrolyze cytidine triphosphate (CTP) (see the Perspective by Funnell). ParB CTP hydrolysis is stimulated by
parS
and regulates the spreading of ParB protein to the
parS
flanking regions, which is crucial for organizing the bacterial chromosome. The cytidine triphosphatase domain is conserved in a large variety of protein sequences, suggesting its potential roles in other cellular processes.

Science
, this issue p.
1129
; see also p.
1072
Coherent spin manipulation of individual atoms on a surface
Authors: Yang Kai , Paul William , Phark Soo-Hyon , Willke Philip , Bae Yujeong , Choi Taeyoung , Esat Taner , Ardavan Arzhang , Heinrich Andreas J. , Lutz Christopher P.
Published: October 2019

Coherent surface spin manipulation

Spin-based quantum information processing requires coherent spin manipulation. Yang
et al.
demonstrate coherent control of surface titanium and iron atom spins on a magnesium oxide surface with a magnetic scanning tunneling microscope tip. Arbitrary sequences of fast electrical pulses delivered to the top induced large electric fields. These fields drove metal-atom movement, which then modulated the tip-atom exchange interaction to create an oscillating effective magnetic field. Advanced spin-control protocols such as Ramsey fringes and Hahn spin echoes revealed quantum dynamics, such as coherent oscillations in a titanium atom dimer assembled on the surface with the tip.

Science
, this issue p.
509
Assessing risk, automating racism
Authors: Benjamin Ruha
Published: October 2019

A health care algorithm reflects underlying racial bias in society
A Loop-Mediated Isothermal Amplification Assay Targeting Neisseria gonorrhoeae
penA
-60.001
Authors: Shimuta Ken , Nakayama Shu-ichi , Takahashi Hideyuki , Ohnishi Makoto
Published: October 2019

Ceftriaxone (CRO) is widely used as the first-line treatment for gonococcal infections. However, CRO-resistant
Neisseria gonorrhoeae
strains carrying mosaic
penA
-60.001 have emerged recently and disseminated worldwide. To meet the urgent need to detect these strains, we report here a loop-mediated isothermal amplification (LAMP) assay system that targets
N. gonorrhoeae
penA
-60.001.
RelZ-Mediated Stress Response in
Mycobacterium smegmatis
: pGpp Synthesis and Its Regulation
Authors: Petchiappan Anushya , Naik Sujay Y. , Chatterji Dipankar
Published: October 2019

Bacteria utilize nucleotide messengers to survive the hostile environmental conditions and the onslaught of attacks within the host. The second messengers guanosine tetraphosphate and pentaphosphate [(p)ppGpp] have a profound impact on the long-term survival, biofilm formation, antibiotic tolerance, virulence, and pathogenesis of bacteria. Therefore, understanding the stress response mechanism regulated by (p)ppGpp is essential for discovering inhibitors of stress response and potential drug targets.
Mycobacterium smegmatis
contains two (p)ppGpp synthetases: Rel
Msm
and RelZ. Our study unravels the novel regulatory mechanisms of RelZ activity and its role in mediating antibiotic tolerance. We further reveal its ability to synthesize novel second messenger pGpp, which may have regulatory roles in mycobacteria.
Strain-Dependent RstA Regulation of Clostridioides difficile Toxin Production and Sporulation
Authors: Edwards Adrianne N. , Krall Ellen G. , McBride Shonna M.
Published: October 2019

Two critical traits of
Clostridioides difficile
pathogenesis are toxin production, which causes disease symptoms, and spore formation, which permits survival outside the gastrointestinal tract. The multifunctional regulator RstA promotes sporulation and prevents toxin production in the historical strain 630Δ
erm
. Here, we show that RstA exhibits stronger effects on these phenotypes in an epidemic isolate, R20291, and additional strain-specific effects on toxin and
rstA
expression are evident. Our data demonstrate that sequence-specific differences within the promoter for the toxin regulator TcdR contribute to the regulation of toxin production by RstA and CodY. These sequence differences account for some of the variability in toxin production among isolates and may allow strains to differentially control toxin production in response to a variety of signals.
Blame and its consequences for healthcare professionals: response to Tigard
Authors: Duthie Elizabeth A , Fischer Ian C , Frankel Richard M
Published: October 2019

Tigard (2019) suggests that the medical community would benefit from continuing to promote notions of individual responsibility and blame in healthcare settings. In particular, he contends that blame will promote systematic improvement, both on the individual and institutional levels, by increasing the likelihood that the blameworthy party will ‘own up’ to his or her mistake and apologise. While we agree that communicating regret and offering a genuine apology are critical steps to take when addressing patient harm, the idea that medical professionals should continue to ‘take the blame’ for medical errors flies in the face of existing science and threatens to do more harm than good. We contrast Dr Tigard’s approach with the current literature on blame to promote an alternative strategy that may help to create lasting change in the face of unfortunate error.
Bilateral single-injection erector spinae plane block versus intrathecal morphine for postoperative analgesia in living donor laparoscopic hepatectomy: a randomized non-inferiority trial
Authors: Kang RyungA , Chin Ki Jinn , Gwak Mi Sook , Kim Gaab Soo , Choi Soo Joo , Kim Jong Man , Choi Gyu-Seong , Ko Justin Sangwook
Published: October 2019

Background

Intrathecal morphine (ITM) provides effective postoperative analgesia in living donor hepatectomy but has significant adverse effects. Studies support the efficacy of erector spinae plane (ESP) blocks in laparoscopic abdominal surgery; we therefore hypothesized that they would provide non-inferior postoperative analgesia compared with ITM and reduce postoperative nausea/vomiting and pruritus. We conducted a randomized, controlled, non-inferiority trial to compare the analgesic efficacy of ITM and bilateral single-injection ESP blocks in laparoscopic donor hepatectomy.

Methods

Fifty-four donors were randomized to receive bilateral ESP blocks with 20 mL 0.5% ropivacaine (n=27) or 400 µg ITM (n=27). Primary outcome was resting pain score 24 hours postoperatively measured on an 11-point numeric rating scale. The prespecified non-inferiority limit was 1. Incidences of postoperative nausea/vomiting and pruritus were assessed.

Results

The mean treatment difference (ESP–ITM) in the primary outcome was 1.2 (95% CI 0.7 to 1.8). The 95% CI upper limit exceeded the non-inferiority limit. Opioid consumption and all other pain measurements were similar between groups up to 72 hours postoperatively. The ESP group had significantly lower incidences of postoperative vomiting (p=0.002) and pruritus (p<0.001).

Conclusions

Bilateral single-injection ESP blocks resulted in higher resting pain scores 24 hours postoperatively compared with ITM and thus did not meet the study definition of non-inferiority. However, the pain intensity with ESP blocks was mild (mean pain scores <3/10) and associated with reduced incidence of postoperative vomiting and pruritus. It warrants further investigation as an analgesic option after laparoscopic living donor hepatectomy.

Trial registration number

KCT0003191.
Development of blue stain in mechanically harvested Scots pine (Pinus sylvestris) logs during storage
Authors: Szewczyk Grzegorz , Jankowiak Robert , Mitka Bartosz , Bożek Piotr , Bilański Piotr , Kulak Dariusz , Barycza Anna , Kunys Grzegorz
Published: October 2019

Blue stain is a type of discoloration that considerably lowers the aesthetic qualities of wood. During harvesting, fungal inoculum finds its way into the wood through places of cutting, delimbing, and damage to the tree stem. The development of peripheral blue stain in the logs of Scots pine (Pinus sylvestris L.) due to damage by a harvester head was investigated, using logs felled and delimbed with a chainsaw as reference. The development of blue stain was related to the age class of the stand, the date of felling, and the microclimatic conditions of the wood storage place. The mean surface area of blue stain in logs produced with the harvester was almost 35 cm2, approximately 30% larger than that of the reference logs. In stands of the fourth age class (diameter at breast height 32 cm), the surface of blue stain was more than two times larger than that of stands of the third age class (diameter at breast height 24 cm). The mean area of blue stain in wood stored after spring felling (19.3 cm2) was about 50% of that after summer felling (38.2 cm2). In particular, the development of blue stain in logs obtained with a harvester was visible between weeks 6 and 9 after spring felling and between weeks 3 and 6 after summer felling. For both felling dates, the range of blue stain depended less on air temperature around the wood stack and depended more on the duration of storage.
Red Ginseng Reduces Inflammatory Response via Suppression MAPK/P38 Signaling and p65 Nuclear Proteins Translocation in Rats and Raw 264.7 Macrophage
Authors: Adam Gareeballah Osman , Kim Gi-Beum , Lee Sei-Jin , Lee Heeryung , Kang Hyung-Sub , Kim Shang-Jin
Published: October 2019

Lipopolysaccharides (LPS) cause systemic inflammatory responses, which are characterized by high mortality and multiple signs, including metabolic disturbances, respiratory acidosis, hypotension, and vital organs disorder. Cytokines secretion and oxidative stress are the main features of the disease. Diagnosis and treatment of systemic inflammation (SI) remain a challenge. Korean Red Ginseng (RG) is one of medicinal herbs that showed a potent anti-oxidant effect. We aimed to study the protective effects of RG on systemic inflammatory response in rats and RAW 264.7 macrophage cells induced by LPS. The rats were treated with water and alcohol extracts of RG for four weeks to prevent the inflammatory response. The result showed that LPS toxin increased morbidity and mortality, and induced liver, kidney, and lung injuries manifested by deteriorated biomarkers. Hypotension, hypomagnesemia, acidosis, and oxidative stress were observed in septic rats. However, RG extracts attenuated liver, kidney, and lung enzymes and metabolites in treated groups via its anti-inflammatory and anti-oxidant properties. Furthermore, RG improved magnesium and blood pressure in the treated groups. RAW 264.7 macrophage cells exposed to LPS disturbance in translocation of p65 and MAPK/p38. Nevertheless, RG-pretreated cells did not significantly alter. In conclusion, RG reduced the rates of mortality and morbidity of treated rats — liver, kidney, and lung injuries were protected in the treated groups through the potentiation of anti-oxidant defense. RG was able to conserve mitochondrial function, inhibiting the activation of MAPK/p38 signaling and suppressing NF-[Formula: see text]B p65 cytoplasm-nucleus transport. Further studies are needed to examine the effects on chronic conditions in animal models and human.
Sterile neutrinos influence on oscillation characteristics of active neutrinos at short distances in the generalized model of neutrino mixing
Authors: Khruschov V. V. , Fomichev S. V.
Published: October 2019

A phenomenological model with active and sterile neutrinos is used for calculations of neutrino oscillation characteristics at the normal mass hierarchy of active neutrinos. Taking into account the contributions of sterile neutrinos, appearance and survival probabilities for active neutrinos are calculated. Modified graphical dependencies for the probability of appearance of electron neutrinos/antineutrinos in muon neutrino/antineutrino beams as a function of the ratio of the distance to the neutrino energy and other model parameters are obtained. It is shown that in the case of a certain type mixing between active and sterile neutrinos it is possible to describe all anomalies of neutrino data at short distances with the same model parameters. A new parametrization for a particular type mixing matrix of active and sterile neutrinos that takes into account the additional sources of CP violation is used. The comparison with the existing experimental data is performed and, using this knowledge, the estimates of some model parameters are found. The theoretical results obtained for mixing of active and sterile neutrinos can be applied for interpretation and prediction of results of ground-based experiments on search of sterile neutrinos as well as for the analysis of some astrophysical data.
Two-dimensional dilaton gravity theory and lattice Schwarzian theory
Authors: Chu Su-Kuan , Ma Chen-Te , Wu Chih-Hung
Published: October 2019

We report a holographic study of a two-dimensional dilaton gravity theory with the Dirichlet boundary condition for the cases of nonvanishing and vanishing cosmological constants. Our result shows that the boundary theory of the two-dimensional dilaton gravity theory with the Dirichlet boundary condition for the case of nonvanishing cosmological constants is the Schwarzian term coupled to a dilaton field, while for the case of vanishing cosmological constant, a theory does not have a kinetic term. We also include the higher derivative term [Formula: see text], where [Formula: see text] is the scalar curvature that is coupled to a dilaton field. We find that the form of the boundary theory is not modified perturbatively. Finally, we show that a lattice holographic picture is realized up to the second-order perturbation of boundary cutoff [Formula: see text] under a constant boundary dilaton field and the nonvanishing cosmological constant by identifying the lattice spacing [Formula: see text] of a lattice Schwarzian theory with the boundary cutoff [Formula: see text] of the two-dimensional dilaton gravity theory.
Efficacy of Isolation as a Control Strategy for Ebola Outbreaks in Combination with Vaccination
Authors: Mukhopadhyay Debkusum , Pal Samares
Published: October 2019

In this research work, we have developed and analyzed a deterministic epidemiological model with a system of nonlinear differential equations for controlling the spread of Ebola virus disease (EVD) in a population with vital dynamics (where birth and death rates are not equal). The model examines the disease transmission dynamics with isolation from exposed and infected human class and effect of vaccination in susceptible human population through stability analysis and bifurcation analysis. The model exhibits two steady state equilibria, namely, disease-free and endemic equilibrium. Next generation matrix method is used to find the expression for [Formula: see text] (the basic reproduction number). Local and global stability of diseases-free equilibrium are shown using nonsingular M-matrix technique and Lyapunov’s theorem, respectively. The existence and local stability of endemic equilibrium are explored under certain conditions. All numerical data entries are supported by various authentic sources. The simulation study is done using MATLAB code 45 which uses Runge–Kutta method of fourth order and we plot the time series and bifurcation diagrams which support our analytical findings. Stability analysis of the model shows that the disease-free equilibrium is locally as well as globally asymptotically stable if [Formula: see text] and endemic equilibrium is locally asymptotically stable in absence of vaccination if [Formula: see text]. Using central manifold theorem, the presence of transcritical bifurcation for a threshold value of the transmission rate parameter [Formula: see text] when [Formula: see text] passes through unity and backward bifurcation (i.e. transcritical bifurcation in opposite direction) for some higher value of [Formula: see text] are established. Our simulation study shows that isolation of exposed and infected individuals can be used as a more effective tool to control the spreading of EVD than only vaccination.
Model calibration for forecasting CO
2
-foam enhanced oil recovery field pilot performance in a carbonate reservoir
Authors: Sharma M. , Alcorn Z. P. , Fredriksen S. B. , Rognmo A. U. , Fernø M. A. , Skjæveland S. M. , Graue A.
Published: October 2019

Application of foam has been found to mitigate challenges associated with field-scale CO
2
floods for enhanced oil recovery (EOR) by providing in-depth mobility control. The field pilots that have been run so far have shown varying results, inferred mainly from inter-well tracer studies and production data analysis. A research collaboration has been set up to advance the technology of using foam as a mobility control agent for CO
2
EOR, with focus on integrated reservoir modelling to assist technology transfer to a high-cost environment. A heterogeneous carbonate reservoir onshore in west Texas, USA has been selected for the field trial. The reservoir has been waterflooded for more than 50 years, and a significant part of it has been on continuous CO
2
injection for the last 5 years. An inverted five-spot pattern, which had rapid CO
2
breakthrough in adjacent producers and is currently recycling significant amounts of CO
2
, has been selected for the study. The pilot is planned for 2 years with surfactant alternating gas (SAG) injection in the first year, followed by CO
2
injection in the next year.

A reservoir model was created by integrating available static and dynamic information. Since the measurement of static information and production performance is usually imprecise, even the most carefully constructed models do not exactly represent reality. In this paper, we present a workflow that was used to calibrate the reservoir model to historical data for practical forecasting, which takes into account a wide range of uncertainties caused by the inaccessibility of information. Laboratory studies were performed with reservoir cores, fluids and selected surfactant to obtain the base values of foam model parameters. As an output, distributions for key performance indicators such as cumulative oil production and CO
2
retention were generated for the proposed pilot to guide further decision-making.

Supplementary material:
The details of simulation set-up and results for history matching and prediction are available at
https://doi.org/10.6084/m9.figshare.c.4704374

This article is part of the Energy Geoscience Series available at
https://www.lyellcollection.org/cc/energy-geoscience-series
Mantle plumes and mantle dynamics in the Wilson cycle
Authors: Heron Philip J.
Published: October 2019

This review discusses the thermal evolution of the mantle following large-scale tectonic activities such as continental collision and continental rifting. About 300 myr ago, continental material amalgamated through the large-scale subduction of oceanic seafloor, marking the termination of one or more oceanic basins (e.g. Wilson cycles) and the formation of the supercontinent Pangaea. The present day location of the continents is due to the rifting apart of Pangaea, with the dispersal of the supercontinent being characterized by increased volcanic activity linked to the generation of deep mantle plumes. The discussion presented here investigates theories regarding the thermal evolution of the mantle (e.g. mantle temperatures and sub-continental plumes) following the formation of a supercontinent. Rifting, orogenesis and mass eruptions from large igneous provinces change the landscape of the lithosphere, whereas processes related to the initiation and termination of oceanic subduction have a profound impact on deep mantle reservoirs and thermal upwelling through the modification of mantle flow. Upwelling and downwelling in mantle convection are dynamically linked and can influence processes from the crust to the core, placing the Wilson cycle and the evolution of oceans at the forefront of our dynamic Earth.
Europe's controversial digital copyright directive finalized
Authors: Samuelson Pamela
Published: October 2019

Considering the new liability risks for ISPs, search engines, and news aggregators under recent EU-wide mandatory rules.
Genioglossus muscle responses to resistive loads in severe OSA patients and healthy control subjects
Authors: Ruehland Warren R. , Rochford Peter D. , Pierce Robert J. , Trinder John , Jordan Amy S. , Cori Jennifer M. , O’Donoghue Fergal J.
Published: October 2019

This study aimed to determine whether there is impairment of genioglossus neuromuscular responses to small negative pressure respiratory stimuli, close to the conscious detection threshold, in obstructive sleep apnea (OSA). We compared genioglossus electromyogram (EMGgg) responses to midinspiratory resistive loads of varying intensity (≈1.2–6.2 cmH2O·L−1·s), delivered via a nasal mask, between 16 severe OSA and 17 control participants while the subjects were awake and in a seated upright position. We examined the relationship between stimulus intensity and peak EMGgg amplitude in a 200-ms poststimulus window and hypothesized that OSA patients would have an increased activation threshold and reduced sensitivity in the relationship between EMGgg activation and stimulus intensity. There was no significant difference between control and OSA participants in the threshold ( P = 0.545) or the sensitivity ( P = 0.482) of the EMGgg amplitude vs. stimulus intensity relationship, where change in epiglottic pressure relative to background epiglottic pressure represented stimulus intensity. These results do not support the hypothesis that deficits in neuromuscular response to negative upper airway pressure exist in OSA during wakefulness; however, the results are likely influenced by a counterintuitive and novel genioglossus muscle suppression response observed in a significant proportion of both OSA and healthy control participants. This suppression response may relate to the inhibition seen in inspiratory muscles such as the diaphragm in response to sudden-onset negative pressure, and its presence provides new insight into the upper airway neuromuscular response to the collapsing force of negative pressure.

NEW & NOTEWORTHY Our study used a novel midinspiratory resistive load stimulus to study upper airway neuromuscular responses to negative pressure during wakefulness in obstructive sleep apnea (OSA). Although no differences were found between OSA and healthy groups, the study uncovered a novel and unexpected suppression of neuromuscular activity in a large proportion of both OSA and healthy participants. The unusual response provides new insight into the upper airway neuromuscular response to the collapsing force of negative pressure.
The critical role of respiratory sinus arrhythmia on temporal cardiac dynamics
Authors: Yeh Chien-Hung , Juan Chung-Hau , Yeh Huei-Ming , Wang Cheng-Yen , Young Hsu-Wen Vincent , Lin Jiunn-Lee , Lin Chen , Lin Lian-Yu , Lo Men-Tzung
Published: October 2019

Temporal cardiac properties provide alternative information in analyzing heart rate variability (HRV), which may be disregarded by the standard HRV analyses. Patients with congestive heart failure (CHF) are known to have distinct temporal features from the healthy individuals. However, the underlying mechanism leading to the variation remains unclear. Whether or not these parameters can finely classify the severity for CHF patients is uncertain as well. In this work, an electrocardiogram was monitored in advanced CHF patients using 24-h Holter in four conditions, including baseline, one and three months after atenolol therapy, and healthy individuals. Slope and area under the curve (AUC) of multiscale entropy (MSE) curve over short (scales 1–5) and long (scales 6–20) scales, and detrended fluctuation analysis (DFA) scaling exponents at short (4–11 beats) and intermediate (>11 beats) window sizes were calculated. The results show that short-time scale MSE-derived parameters (slope: −0.08 ± 0.10, −0.03 ± 0.10, 0.02 ± 0.06, 0.08 ± 0.06; AUC: 4.03 ± 2.11, 4.69 ± 1.28, 4.73 ± 0.94, and 6.17 ± 1.23) and short-time scale DFA exponent (0.79 ± 0.16, 0.95 ± 0.22, 1.11 ± 0.19, and 1.35 ± 0.20) can hierarchically classify all four conditions. More importantly, simulated R-R intervals with different fractions and amplitude of respiratory sinus arrhythmia (RSA) components were examined to validate our hypothesis regarding the essentiality of RSA in the improvement of cardiovascular function, and its tight association with unpredictability and fractal property of HRV, which is in line with our hypothesis that RSA contributes significantly to the generation of the unpredictability and fractal behavior of HR dynamics.

NEW & NOTEWORTHY Temporal cardiac properties provide useful diagnostic parameters for patients with congestive heart failure (CHF). Our study hierarchically classified CHF patients with β-blocker treatment by using multiscale entropy and detrended fluctuation analysis. Also, we provided the evidence to validate the critical role of respiratory sinus arrhythmia in the fractal properties of heart rate variability.
Dissociating the effects of oxygen pressure and content on the control of breathing and acute hypoxic response
Authors: Dominelli Paolo B. , Baker Sarah E. , Wiggins Chad C. , Stewart Glenn M. , Sajgalik Pavol , Shepherd John R. A. , Roberts Shelly K. , Roy Tuhin K. , Curry Timothy B. , Hoyer James D. , Oliveira Jennifer L. , Foster Glen E. , Joyner Michael J.
Published: October 2019

Arterial oxygen tension and oxyhemoglobin saturation ([Formula: see text]) decrease in parallel during hypoxia. Distinguishing between changes in oxygen tension and oxygen content as the relevant physiological stimulus for cardiorespiratory alterations remains challenging. To overcome this, we recruited nine individuals with hemoglobinopathy manifesting as high-affinity hemoglobin [HAH; partial pressure at 50% [Formula: see text] (P50) = 16 ± 0.4 mmHg] causing greater [Formula: see text] at a given oxygen partial pressure compared with control subjects ( n = 12, P50 = 26 ± 0.4 mmHg). We assessed ventilatory and cardiovascular responses to acute isocapnic hypoxia, iso-oxic hypercapnia, and 20 min of isocapnic hypoxia (arterial Po2 = 50 mmHg). Blood gas alterations were achieved with dynamic end-tidal forcing. When expressed as a function of the logarithm of oxygen partial pressure, ventilatory sensitivity to hypoxia was not different between groups. However, there was a significant difference when expressed as a function of [Formula: see text]. Conversely, the rise in heart rate was blunted in HAH subjects when expressed as a function of partial pressure but similar when expressed as a function of [Formula: see text]. Ventilatory sensitivity to hypercapnia was not different between groups. During sustained isocapnic hypoxia, the rise in minute ventilation was similar between groups; however, heart rate was significantly greater in the controls during 3 to 9 min of exposure. Our results support the notion that oxygen tension, not content, alters cellular Po2in the chemosensors and drives the hypoxic ventilatory response. Our study suggests that in addition to oxygen partial pressure, oxygen content may also influence the heart rate response to hypoxia.

NEW & NOTEWORTHY We dissociated the effects of oxygen content and pressure of cardiorespiratory regulation studying individuals with high-affinity hemoglobin (HAH). During hypoxia, the ventilatory response, expressed as a function of oxygen tension, was similar between HAH variants and controls; however, the rise in heart rate was blunted in the variants. Our work supports the notion that the hypoxic ventilatory response is regulated by oxygen tension, whereas cardiovascular regulation may be influenced by arterial oxygen content and tension.
A New and Practical Reliability Allocation Method for a Complex System of NC Turrets
Authors: Hu Wei , Chen Fei , Wang Yankun , Xie Qunya
Published: October 2019

Existing methods cannot satisfy the reliability allocation demands of the early design phase for the modern complex system of NC turrets. Motivated by the need of practical application, this paper proposes a new and practical reliability allocation method in the early design stage for NC turrets considering failure mode and system complexity, information inaccessibility, and expert knowledge limitation. First, the fault tree of a NC turret is quickly built to clear the relationship between the system’s compositions and failure modes up. Second, the happening probability of each failure event in the fault tree is firstly calculated by fuzzy expert evaluation to provide the reliability allocation with complete information. Third, by discussing the practical meaning of every layer in the fault tree, the proposed allocation strategy is within the experts’ knowledge scope for evaluating accurately. Eventually, the application result of the AK36100 A turret is presented and compared with some existing allocation methods, illustrating the rationality of the proposed allocation method.
Conversion of Organic Matter in Coal by Photocatalytic Oxidation with H2O2 over SFC/TiO2 in Isolated Oxygen System
Authors: Xie Heng-Shen , Zong Zhi-Min , Wang Yu-Gao , Zhao Pei-Zhi , Zhang Shi-Hua , Wang Jun-Qiang , Fu Hong , Liang Shuang-Hua , Su Ling , Wei Xian-Yong
Published: October 2019

Shenfu bituminous coal (SFBC), Geting coal (GTC), Shengli lignite (SLL), and Holingola coal (HLGLC) were oxidized by UV light radiation with aqueous H2O2 over SFC/TiO2 in a closed suspension system (CSS) to understand structural characteristics of 4 typical Chinese coals. Raw and oxidized coals were dried and extracted with acetone thoroughly to ensure residue extraction. Meanwhile, the extracts were analyzed using a gas chromatograph/mass spectrometer. The results show that organic matters (OMs) in coals can be converted into a large number of oxygen-containing organic compounds (OCOCs), mainly containing ketones, esters, alcohols, etc. Oxidizing species such as hydroxyls, hydroperoxyl, and alkyl radicals are excited by light irradiation and substitute for hydrogen atoms of methyls and methylenes of acenes or branched-chain alkanes in coals. Acetic acid and acetaldehyde can be formed and dissolved in aqueous solution in the oxidation reaction. The yields can be improved with the enhancement of the oxidation effect.