bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of a Kinase-Active CheA Conformation in Escherichia coli Chemoreceptor Signaling Complexes
Authors: Piñas Germán E. , Parkinson John S.
Published: September 2019

Regulation of CheA kinase in chemoreceptor arrays is critical for
Escherichia coli
chemotaxis. However, to date, little is known about the CheA conformations that lead to the kinase-on or kinase-off states. Here, we explore the signaling roles of a distinct conformation of the ATP-binding CheA.P4 domain identified by all-atom molecular dynamics simulation. Amino acid replacements at residues predicted to stabilize the so-called “dipped” CheA.P4 conformation abolished the kinase activity of CheA and its ability to support chemotaxis. Our findings indicate that the dipped conformation of the CheA.P4 domain is critical for reaching the kinase-active state in chemoreceptor signaling arrays.
The Ancestral Lhasa River: A Late Cretaceous trans-arc river that drained the proto–Tibetan Plateau
Authors: Laskowski Andrew K. , Orme Devon A. , Cai Fulong , Ding Lin
Published: September 2019

Late Cretaceous trench basin strata were deposited in the subduction zone that consumed Neo-Tethyan oceanic lithosphere along the southern margin of the proto–Tibetan Plateau. We conducted detrital zircon (DZ) U-Pb geochronology on six trench basin samples (n = 1716) collected near Dênggar, Tibet (∼500 km west of Lhasa), to assess the provenance of these rocks and reconstruct Late Cretaceous sediment transport pathways. They contained DZ ages that point to a unique source around Lhasa city, north of the Late Cretaceous Gangdese magmatic arc. The modern Lhasa River catchment contains the requisite sources, and its main trunk transects the Gangdese magmatic arc, joining with the Yarlung River at a barbed junction at the India-Asia suture. We infer that the Lhasa River is an ancient feature that transported sediment to the subduction zone in Late Cretaceous time and persisted during India-Asia collision.
Temporal and spatial variations in magmatism and transpression in a Cretaceous arc, Median Batholith, Fiordland, New Zealand
Authors: Buriticá Luisa F. , Schwartz Joshua J. , Klepeis Keith A. , Miranda Elena A. , Tulloch Andy J. , Coble Matthew A. , Kylander-Clark Andrew R.C.
Published: September 2019

We investigated the interplay between deformation and pluton emplacement with the goal of providing insights into the role of transpression and arc magmatism in forming and modifying continental arc crust. We present 39 new laser-ablation–split-stream–inductively coupled plasma–mass spectrometry (LASS-ICP-MS) and secondary ion mass spectrometry (SIMS) 206Pb/238U zircon and titanite dates, together with titanite geochemistry and temperatures from the lower and middle crust of the Mesozoic Median Batholith, New Zealand, to (1) constrain the timing of Cretaceous arc magmatism in the Separation Point Suite, (2) document the timing of titanite growth in low- and high-strain deformational fabrics, and (3) link spatial and temporal patterns of lithospheric-scale transpressional shear zone development to the Cretaceous arc flare-up event. Our zircon results reveal that Separation Point Suite plutonism lasted from ca. 129 Ma to ca. 110 Ma in the middle crust of eastern and central Fiordland. Deformation during this time was focused into a 20-km-wide, arc-parallel zone of deformation that includes previously unreported segments of a complex shear zone that we term the Grebe shear zone. Early deformation in the Grebe shear zone involved development of low-strain fabrics with shallowly plunging mineral stretching lineations from ca. 129 to 125 Ma. Titanites in these rocks are euhedral, are generally aligned with weak subsolidus fabrics, and give rock-average temperatures ranging from 675 °C to 700 °C. We interpret them as relict magmatic titanites that grew prior to low-strain fabric development. In contrast, deformation from ca. 125 to 116 Ma involved movement along subvertical, mylonitic shear zones with moderately to steeply plunging mineral stretching lineations. Titanites in these shear zones are anhedral grains/aggregates that are aligned within mylonitic fabrics and have rock-average temperatures ranging from ∼610 °C to 700 °C. These titanites are most consistent with (re)crystallization in response to deformation and/or metamorphic reactions during amphibolite-facies metamorphism. At the orogen scale, spatial and temporal patterns indicate that the Separation Point Suite flare-up commenced during low-strain deformation in the middle crust (ca. 129–125 Ma) and peaked during high-strain, transpressional deformation (ca. 125–116 Ma), during which time the magmatic arc axis widened to 70 km or more. We suggest that transpressional deformation during the arc flare-up event was an important process in linking melt storage regions and controlling the distribution and geometry of plutons at mid-crustal levels.
Ambulatory Smoking Habits Investigation based on Physiology and Context (ASSIST) using wearable sensors and mobile phones: protocol for an observational study
Authors: Zhai Donghui , Schiavone Giuseppina , Van Diest Ilse , Vrieze Elske , DeRaedt Walter , Van Hoof Chris
Published: September 2019

Introduction

Smoking prevalence continues to be high over the world and smoking-induced diseases impose a heavy burden on the medical care system. As believed by many researchers, a promising way to promote healthcare and well-being at low cost for the large vulnerable smoking population is through eHealth solutions by providing self-help information about smoking cessation. But in the absence of first-hand knowledge about smoking habits in daily life settings, systems built on these methods often fail to deliver proactive and tailored interventions for different users and situations over time, thus resulting in low efficacy. To fill the gap, an observational study has been developed on the theme of objective and non-biased monitoring of smoking habits in a longitudinal and ambulatory mode. This paper presents the study protocol. The primary objective of the study is to reveal the contextual and physiological pattern of different smoking behaviours using wearable sensors and mobile phones. The secondary objectives are to (1) analyse cue factors and contextual situations of smoking events; (2) describe smoking types with regard to users’ characteristics and (3) compare smoking types between and within subjects.

Methods and analyses

This is an observational study aimed at reaching 100 participants. Inclusion criteria are adults aged between 18 and 65 years, current smoker and office worker. The primary outcome is a collection of a diverse and inclusive data set representing the daily smoking habits of the general smoking population from similar social context. Data analysation will revolve around our primary and secondary objectives. First, linear regression and linear mixed model will be used to estimate whether a factor or pattern have consistent (p value<0.05) correlation with smoking. Furthermore, multivariate multilevel analysis will be used to examine the influence of smokers’ characteristics (sex, age, education, socioeconomic status, nicotine dependence, attitudes towards smoking, quit attempts, etc), contextual factors, and physical and emotional statuses on their smoking habits. Most recent machine learning techniques will also be explored to combine heterogeneous data for classification of smoking events and prediction of craving.

Ethics and dissemination

The study was designed together by an interdisciplinary group of researchers, including psychologist, psychiatrist, engineer and user involvement coordinator. The protocol was reviewed and approved by the ethical review board of UZ Leuven on 18 April 2016, with an approval number S60078. The study will allow us to characterise the types of smokers and triggering events. These findings will be disseminated through peer-reviewed articles.
Doctor, how can we help you? Qualitative interview study to identify key interventions to target burnout in hospital doctors
Authors: Walsh Gillian , Hayes Blánaid , Freeney Yseult , McArdle Siobhain
Published: September 2019

Objective

To identify priority interventions for the prevention and reduction of work stress and burnout in hospital doctors through analysis of (1) doctors’ experiences of work stress and burnout and (2) their preferences with respect to interventions.

Design

Qualitative design using semistructured interviews analysed with deductive thematic analysis.

Setting

Hospitals in Ireland.

Participants

32 hospital doctors (16 practising consultants and 16 doctors in training) from a range of specialties, career stages, hospital types and locations.

Results

Practical, system-focused interventions were found to be most needed. Challenges with basic entitlements, that is, accessing statutory leave, knowing in advance when leave can be taken and being adequately covered when on leave were identified as requiring urgent attention. Other priority interventions identified were the integration of psychological support in the everyday working environment, time and training for clinical line managers to perform key management activities such as debriefing and education interventions which highlight work stress risks and care pathways, teach self-care and train doctors in how to support one another.

Conclusions

Hospital doctors are feeling the effects of greater demand and fewer resources. What they most urgently need is adequate staffing levels, access to statutory leave and adequate cover when on leave. Doctors do not receive the support they need from their clinical line managers, who lack the skills and time to excel as people managers. Organisations should focus on developing clinical management skills across the system. The culture of medicine needs to change from stigmatisation and competitiveness to compassion and collaboration. Organisations, medical schools and professional bodies can steer this change through education.
Fatty liver index as a predictor of increased risk of cardiometabolic disease: finding from the Kuopio Ischaemic Heart Disease Risk Factor Study Cohort
Authors: Olubamwo Olubunmi O. , Virtanen Jyrki K. , Pihlajamaki Jussi , Mantyselka Pekka , Tuomainen Tomi-Pekka
Published: September 2019

Objective

Fatty liver disease (FLD), a global epidemic, is also a predictor of cardiometabolic disease (CMD) (type 2 diabetes or cardiovascular disease). Our objective was to examine whether progressive FLD, as assessed by fatty liver index (FLI), predicts increasing future CMD risk compared with relatively stable FLD, among middle-aged men.

Design

Prospective epidemiological study.

Setting

University affiliated research centre in Kuopio, Eastern Finland.

Participants

Our subjects were 501 men without CMD during the initial 4-year follow-up in the Kuopio Ischaemic Heart Disease Risk Factor Study cohort.

Outcome measure

Over the initial 4-year follow-up, 135 men (26.9%) had a significant (≥10) FLI increase. The association of 4-year FLI increase with incident CMD was analysed in multivariable-adjusted Cox regression models, adjusting for baseline constitutional and lifestyle factors (model 1) and, in addition, metabolic and inflammation biomarker factors (model 2).

Results

During a mean follow-up of 15 years, 301 new CMD cases occurred. We used subjects with low baseline FLI and no significant 4-year FLI increase as the reference. For subjects with intermediate baseline FLI and significant 4-year FLI increase, the HRs and 95% CIs for incident CMD in model 1 (2.13 (1.45 to 3.13)) and model 2 (1.73 (1.13 to 2.66)) exceeded values for subjects with similar baseline FLI without a significant 4-year change (HRs (95% CIs) were 1.36 (0.94 to 1.97) for model 1 and 1.18 (0.81 to 1.70) for model 2). They approached HRs (95% CI) for subjects who maintained high FLI over the 4 years (HRs (95% CIs) were 2.18 (1.54 to 3.10) in model 1 and 1.85 (1.21 to 2.82) in model 2).

Conclusion

Persons with significant FLI increase are likely with increasing CMD risk. Such persons should be evaluated for progressive FLD and CMD and managed to reduce CMD risk.
Haemoglobin concentration and survival of haemodialysis patients before and after experiencing cardiovascular disease: a cohort study from Japanese dialysis outcomes and practice pattern study (J-DOPPS)
Authors: Kido Ryo , Akizawa Tadao , Fukuhara Shunichi
Published: September 2019

Objectives

Differences in the association of haemoglobin concentration with mortality or adverse cardiovascular events in haemodialysis patients before and after experiencing cardiovascular disease are unclear. We aimed to assess the influence of cardiovascular-comorbid condition on the association between haemoglobin concentration and mortality.

Design

A prospective cohort study.

Setting

The Dialysis Outcomes and Practice Patterns Study Dialysis in phases 2 to 4 (2002 to 2011), including 80 randomly selected dialysis facilities in Japan (J-DOPPS).

Participants

5515 adult haemodialysis patients.

Primary and secondary outcome measures

Primary outcome was all-cause mortality. Cardiovascular mortality and adverse cardiovascular events were also evaluated. The association of these outcomes with haemoglobin concentration, categorised into six classes by 1.0 g/dL units, and cardiovascular-comorbid condition, treated as a time-dependent variable updated every 4 months, was evaluated. Adjusted hazard ratios (aHRs) were computed using a time-dependent Cox model with interaction test for cardiovascular comorbidity.

Results

Over a median 2.0 years, 847 all-cause and 326 cardiovascular deaths, and 1000 adverse cardiovascular events occurred. Compared with haemoglobin 11.0 to 11.9 g/dL, the aHRs of mortality at the lowest range (<9.0 g/dL) were 1.29 (95% CI 0.95 to 1.76) and 2.11 (95% CI 1.47 to 3.06) in cardiovascular-comorbid and non-cardiovascular-comorbid patients, respectively (p=0.04 for cardiovascular-comorbid interaction), with increased cardiovascular mortality in both groups. At the second-lowest range (9.0 to 9.9 g/dL), mortality was increased only in non-cardiovascular-comorbid patients. Respective risks for mortality and adverse cardiovascular events at the second-highest range (12.0 to 12.9 g/dL) were non-significant but increased in both groups, while adverse cardiovascular events were increased at the highest range (≥13.0 g/dL) in non-cardiovascular-comorbid patients.

Conclusions

The association of low haemoglobin concentration with all-cause mortality differed between haemodialysis patients with and without cardiovascular comorbidity. Cardiovascular-comorbid condition should be considered when the association of haemoglobin concentration with mortality is addressed.
Scoping review protocol: effectiveness of individualised nutritional care plans to reduce malnutrition during hospitalisation and up to 3 months after discharge
Authors: Ingstad Kari , Uhrenfeldt Lisbeth , Kymre Ingjerd Gåre , Skrubbeltrang Conni , Pedersen Preben Ulrich
Published: September 2019

Introduction

More than 20% of patients are malnourished after hospitalisation. Malnutrition may negatively impact patients’ outcomes as it increases the risk of complications, morbidity, mortality and loss of function. However, hospital-initiated transitional care can improve some outcomes in hospitalised adult patients. The objective of this scoping review is to map the literature that assesses the effectiveness of individualised nutritional care plans to reduce malnutrition during hospitalisation and for the first 3 months after discharge.

Methods and analysis

This protocol is based on the framework outlined by Arksey and O’Malley. The search strategy was developed by a medical librarian. We will search for relevant literature from the following databases: MEDLINE via PubMed, Cumulative Index to Nursing and Allied Health Literature, and Embase. We will also search the reference lists of included studies. Two independent reviewers will screen abstracts and full articles in parallel, from the included studies using specific inclusion and exclusion criteria. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols checklist facilitated the preparation of this research protocol. The scoping review will provide a narrative account of the findings from the existing literature through thematic content analysis of the extracted literature.

Ethics and dissemination

Since all data will be obtained from publicly available materials, research ethics approval is not required for this scoping review. The research findings will be submitted for publication in a relevant open-access peer-reviewed journal and presented at relevant conferences.
Pulmonary artery size is associated with functional clinical status in the Fontan circulation
Authors: Ridderbos Floris-Jan S , Bonenkamp Bregje E , Meyer Sophie L , Eshuis Graziella , Ebels Tjark , van Melle Joost P , Willems Tineke P , Berger Rolf M F
Published: September 2019

Objective

In the Fontan circulation, non-pulsatile pulmonary blood flow is suggested to negatively affect pulmonary artery growth. The pulmonary vasculature is regarded a key determinant of outcome after Fontan completion. We hypothesised that in Fontan patients pulmonary artery size correlates with follow-up and functional clinical status.

Methods

This is a single-centre, cross-sectional cohort study. Thirty-nine paediatric and adult Fontan patients with a concomitant cardiac magnetic resonance (CMR) scan and a cardiopulmonary exercise test between 2012 and 2013 were included. CMR-derived left and right pulmonary artery cross-sectional areas were expressed as Nakata index. Functional status was defined as peak oxygen consumption (pVO2) indexed for weight, as percentage of predicted (pred) and as New York Heart Association Functional Class (NYHA-FC).

Results

Age at CMR was 18±7.2 years. Time since Fontan completion was 11.9±7.4 years. Nakata index was lower versus the reference values (238.6±78.5 vs 330±30 mm2/m2, p<0.001). Nakata index correlated negatively with age at CMR (r=−0.393, p=0.013) and time since Fontan completion (r=−0.341, p=0.034). pVO2 was 27.9±8.9 mL/min/kg and pVO2pred was 58.1%±14.1%. Nakata index correlated positively with pVO2 (r=0.468, p=0.003) and pVO2pred (r=0.353, p=0.028). Nakata index correlated negatively with NYHA-FC (r=−0.450, p=0.004). Nakata index was an independent predictor (β=0.359, p=0.007) for pVO2 (adjusted R2=0.442, with maximum heart rate and oxygen pulse at peak exercise).

Conclusions

Pulmonary artery size expressed as Nakata index is a novel independent predictor for functional clinical status. Nakata index negatively correlated with follow-up duration, suggesting that chronic abnormal non-pulsatile pulmonary blood flow plays a role in lagging pulmonary arterial growth in the Fontan circulation.
Similar maximal oxygen uptake assessment from a step cycling incremental test and verification tests on the same or different day
Authors: Possamai Leonardo Trevisol , Campos Fernando de Souza , Salvador Paulo Cesar do Nascimento , de Aguiar Rafael Alves , Guglielmo Luiz Guilherme Antonacci , de Lucas Ricardo Dantas , Caputo Fabrizio , Turnes Tiago
Published: September 2019

The present study aimed to compare maximal oxygen uptake of a step incremental test with time to exhaustion verification tests (TLIM) performed on the same or different day. Nineteen recreationally trained cyclists (age: 23 ± 2.7 years; maximal oxygen uptake: 48.0 ± 5.8 mL·kg−1·min−1) performed 3 maximal tests as follows: (i) same day: an incremental test with 3-min stages followed by a TLIM at 100% of peak power output of the incremental test (TLIM-SAME) interspaced by 15 min; and (ii) different day: a TLIM at 100% of peak power output of the incremental test (TLIM-DIFF). The maximal oxygen uptake was determined for the 3 tests. The maximal oxygen uptake was not different among the tests (incremental: 3.83 ± 0.41; TLIM-SAME: 3.72 ± 0.42; TLIM-DIFF: 3.75 ± 0.41 L·min−1; P = 0.951). Seven subjects presented a variability greater than ±3% in both verification tests compared with the incremental test. The same-day verification test decreased the exercise tolerance (240 ± 38 vs. 310 ± 36 s) compared with TLIM-DIFF (P < 0.05). In conclusion, the incremental protocol is capable of measuring maximal oxygen uptake because similar values were observed in comparison with verification tests. Although the need for the verification phase is questionable, the additional tests are useful to evaluate individual variability. Novelty Step incremental test is capable of measuring maximal oxygen uptake with similar values during TLIM on the same or different day. Although the necessity of the verification phase is questionable, it can allow the determination of variability in maximal oxygen uptake.
Understanding gas bubble trauma in an era of hydropower expansion: how do fish compensate at depth?
Authors: Pleizier Naomi K. , Nelson Charlotte , Cooke Steven J. , Brauner Colin J.
Published: September 2019

Hydrostatic pressure is known to protect fish from damage by total dissolved gas (TDG) supersaturation, but empirical relationships are lacking. In this study we demonstrate the relationship between depth, TDG, and gas bubble trauma (GBT). Hydroelectric dams generate TDG supersaturation that causes bubble growth in the tissues of aquatic animals, resulting in sublethal and lethal effects. We exposed fish to 100%, 115%, 120%, and 130% TDG at 16 and 63 cm of depth and recorded time to 50% loss of equilibrium and sublethal symptoms. Our linear model of the log-transformed time to 50% LOE (R2= 0.94) was improved by including depth. Based on our model, a depth of 47 cm compensated for the effects of 4.1% (±1.3% SE) TDG supersaturation. Our experiment reveals that once the surface threshold for GBT from TDG supersaturation is known, depth protects rainbow trout (Oncorhynchus mykiss) from GBT by 9.7% TDG supersaturation per metre depth. Our results can be used to estimate the impacts of TDG on fish downstream of dams and to develop improved guidelines for TDG.
The effect of dioxidovanadium complex (V) on hepatic function in streptozotocin-induced diabetic rats
Authors: Sibiya Samukelisiwe , Msibi Bonisiwe , Khathi Andile , Sibiya Ntethelelo , Booysen Irvin , Ngubane Phikelelani
Published: September 2019

Diabetics are susceptible to hepatic dysfunction risks due to hyperglycaemia and insulin therapy. Conventional diabetes treatments improve glycaemic control; however, hepatic hazards associated with these agents remains a challenge. Accordingly, this study sought to investigate the effect of a dioxidovanadium complex (V) on the hepatic function in streptozotocin-induced diabetic rats. Sprague-Dawley rats (240–250 g) were divided into 4 groups (n = 6): nondiabetic control, diabetic control, insulin-treated, and vanadium complex groups. The dioxidovanadium (10, 20, and 40 mg/kg) was administered twice every 2nd day for 5 weeks and blood glucose concentration was monitored weekly. At the end of the experimental period, all the experimental groups were sacrificed, and then the lipid profile, liver superoxide dismutase, glutathione peroxidase and malondialdehyde, plasma alanine aminotransferase and aspartate aminotransferase, and C-reactive protein (CRP) concentration were measured. The administration of dioxidovanadium significantly alleviated hyperglycaemia with concomitant attenuation in oxidative stress as evidenced by reduced malondialdehyde concentrations. Furthermore, vanadium complex abolished diabetes-induced dyslipidaemia. Lastly, vanadium complex administration attenuated the increase in alanine aminotransferase, aspartate aminotransferase, and plasma C-reactive protein. These findings suggest that this metallo-compound (dioxidovanadium) may ameliorate liver dysfunction often observed in diabetes.
Regulatory mechanisms of leaf color change in Acer pictum subsp. mono
Authors: Ge Wei , Wang Xiaoxiao , Li Jianyi , Zhu Wenpeng , Cui Jinteng , Zhang Kezhong
Published: September 2019

Acer pictum subsp. mono is a colored leaf tree with vital ornamental and economic value. However, insufficient color change and early leaf fall in cities restrict its ornamental value. In this research, green and red leaves from wild A. p. subsp. mono were collected to study the regulatory mechanisms of leaf color change. Through the determination of plant physiological indexes, we found that the photosynthetic pigment content in red leaves decreased significantly compared with green leaves, while the anthocyanin content and antioxidant activity increased significantly compared with green leaves during the leaf color change process. Using transcriptome sequencing, we found more than 5500 differentially expressed genes, most of which were up-regulated. Many of the differentially expressed genes are involved in the anthocyanin metabolic pathway. The expression patterns of 15 key genes were investigated by quantitative real-time polymerase chain reaction. Among these genes, AmDFR and PAL1 are significant genes involved in the anthocyanin metabolic pathway, and CIPKs2, CIPKs6, CMLs1, CMLs38, AmGST1, AmGST2, GPX3, CBF, AmAPX, AmSOD, POD5, AmGR, and PSBY might be stress response genes that indirectly regulated the anthocyanin accumulation. The results showed that these genes play vital roles in the leaf color change of A. p. subsp. mono. This research will be helpful in further study of the molecular regulatory mechanisms of leaf color change and for the improvement of colored leaf plants.
Polymer matrix ferroelectric composites under pressure: Negative electric capacitance and glassy dynamics
Authors: Starzonek Szymon , Drozd-Rzoska Aleksandra , Rzoska Sylwester J. , Zhang Kena , Pawlikowska Emilia , Kȩdzierska-Sar Aleksandra , Szafran Mikolaj , Gao Feng
Published: September 2019

This report presents the results of high-pressure and broadband dielectric spectroscopy studies in polyvinylidene difluoride (PVDF) and barium strontium titanate (BST) microparticles composites (BST/PVDF). It shows that the Arrhenius behaviour for the temperature-related dynamics under atmospheric pressure is coupled to Super-Arrhenius/Super-Barus isothermal pressure changes of the primary relaxation time. Following these results, an explanation of the unique behaviour of the BST/PVDF composite is proposed. Subsequently, it is shown that when approaching the GPa domain the negative electric capacitance phenomenon occurs.

Graphical abstract
Entanglement of two distant quantum dots with the flip-flop interaction coupled to plasmonic waveguide
Authors: Ko Myong-Chol , Kim Nam-Chol , Ryom Ju-Song , Ri Su-Ryon , Li Jian-Bo
Published: September 2019

The entanglement of two distant quantum dots coupled to metallic waveguide has been investigated theoretically in the presence of the flip-flop interaction with the analytic solutions of eigenvalue equations of the system. High entanglement of two quantum dots could be achieved by adjusting the direct-coupling strength of two quantum dots, the coupling strength of quantum dots with surface plasmon along metallic waveguide, the group velocity of surface plasmon and detuning. The discussed system with the flip-flop interaction provides us with a rich way to realize the quantum device for quantum information processing, such as quantum communication and quantum computation.
The characteristics of laser scattered by droplets
Authors: Zhang Bin , Zhang Yu , Li Yunxi , Li Qingyan , Bai Yuru , Yan Shiyu , Cui Tiankai , Wang Chunhui
Published: September 2019

Droplets are the primary factors which influence laser transmitting in bad weather. This paper researches the analytic expression of droplets influencing the laser, which is based on the geometric optic theory and distribution of raindrop size and shape. In this paper, the relationship between the incidence and emergence angle of droplets is discussed. The effects of an individual raindrop on Ladar divergence angle, illuminance and optical path difference are investigated, and then the cumulated influence of a large quantity of raindrops is analyzed. The illuminance of scanning the targets and laser radar received by the detector is presented.
Two-dimensional Bose polaron using diffusion Monte Carlo method
Authors: Akaturk E. , Tanatar B.
Published: September 2019

We investigate the properties of a mobile impurity immersed in a two-dimensional (2D) Bose gas at zero temperature using quantum Monte Carlo (QMC) methods. The repulsive boson–boson and impurity-boson interactions are modeled by hard-disk potentials with positive scattering lengths a and b, respectively, taken to be equal to the scattering lengths. We calculate the polaron energy and effective mass for the density parameter na2 [Formula: see text] 1 and the ratio a/b. We find that at low densities perturbation theory adequately describes the simulation results. As the impurity-boson interaction strength increases, the polaron mass is enhanced. Additionally, we calculate the structural properties of the Bose system, such as the impurity-boson pair-correlation function and the change of the density profile around the impurity.
Isolated attosecond pulse generation from different frequency-chirping combined fields
Authors: Liu Hui , Liu Hang , Feng Liqiang
Published: September 2019

Generation of high-order harmonic spectrum and isolated attosecond pulse (IAP) from frequency-chirping combined field has been investigated. It is found that by adding the middle-chirp form of the laser field, the extension of the harmonic cutoff comes from the middle region of the laser field. However, the intensity of the higher-order spectral continuum is very low. By adding the asymmetric negative chirp form of the laser field, the extension of the harmonic cutoff is attributed to the falling region of the laser field. Moreover, the intensity of the higher-order spectral continuum presents similar value as that produced from the chirp-free pulse. Further, by properly adding a second controlling pulse (i.e., infrared field or ultraviolet pulse) into the fundamental chirped pulse, the intensity of the harmonic spectrum can be enhanced by 2–3 and 1–2 orders of magnitudes for the cases of the middle-chirp form and the asymmetric negative chirp form, respectively. Finally, by using the best laser conditions, a series of isolated attosecond pulses with the durations of 38 as can be produced.
Excitatory electromagnetic induction current enhances coherence resonance of the FitzHugh–Nagumo neuron
Authors: Jia Yanbing , Lu Bo , Gu Huaguang
Published: September 2019

The effect of electromagnetic induction on neural firing activities has been widely investigated and has also been related to neural information coding. In this study, electromagnetic induction and Gaussian white noise (GWN) are introduced to the FitzHugh–Nagumo neuron, and the effect of induction current on GWN-induced coherence resonance (CR) is investigated. For an appropriate value of bias voltage source, the induction current is excitatory (respectively, inhibitory) when the gain of induction current is positive (respectively, negative). When the induction current is excitatory, the degree of CR is enhanced. When the induction current is inhibitory, however, the degree of CR is weakened. Furthermore, by varying the value of bias voltage source, we show that the degree of CR increases with the increase in the gain of induction current. Bifurcation analysis shows that the supercritical Hopf bifurcation point gets close to the resting state with the increase in the gain of induction current, which causes the increase in the degree of CR. The results of this study show that excitatory electromagnetic induction current can enhance noise-induced CR. This finding provides a possible way to modulate CR of the nervous system.
Results on t-Fuzzy Graphs
Authors: Borzooei R. A. , Sheikh Hoseini B. , Mohseni Takallo M.
Published: September 2019

It is much more practical to use the [Formula: see text]-norm than the minimum in defining the fuzzy graph. Hence, the concept of [Formula: see text]-fuzzy graph was introduced by Mordeson et al. in [J. N. Mordeson and S. Mathew, [Formula: see text]-norm Fuzzy Graphs, New Mathematics and Natural Computation 14(1) (2018) 129–143]. In this paper, we concentrate on the relatively new concept of fuzzy adjacency matrix of that [Formula: see text]-fuzzy graphs. The purpose of this paper is to further develop a product of this fuzzy adjacency matrix based on [Formula: see text]-fuzzy graphs. Moreover, two kinds of Boolean matrix are defined and relation between Normal Boolean matrix, product of adjacency matrix and 1-level cut Boolean matrix is obtained.
A new exploration tool for subtle stratigraphic traps in the offshore Nile Delta, Egypt
Authors: Lala Amir M. S. , Talaat Amr
Published: September 2019

The offshore Nile Delta Basin is considered as one of the most promising hydrocarbon provinces in Egypt, with an excellent potential for gas and condensate reserves following future exploration. Most of the discoveries in this basin, such as the reservoirs of the Upper Miocene and the Middle–Upper Pliocene, have been enabled by the use of a direct hydrocarbon indicator (DHI), based on a class III seismic amplitude v. offset (AVO) anomaly. However, there are gas-bearing formations in the Lower Pliocene that have been successfully tested where the sand did not show any seismic amplitude anomaly in full stacks or in near- and far-offset sub-stacks. The AVO analysis of this sand reservoir is referred to as AVO class II-P. Another case of a subtle AVO class I anomaly in a Lower Pliocene gas reservoir has also been tested by three wells.

These variations in AVO types push us to find a new methodology to reduce the risk of unsuccessful exploration wells, mainly using seismic data. The enhanced AVO pseudo-gradient attribute (EAP) has previously been used in other studies, mainly to highlight AVO class III anomalies. However, in the present paper, we demonstrate a workflow to identify all the principal AVO classes observed in this province. Computing the EAP attribute from our data, we find that AVO class I has negative EAP values, while the other classes have positive values. Class III and classes II and II-P may be distinguished from each other as the former yields a strong positive EAP value, whereas the latter two classes yield weak EAP responses.

After determining the AVO class, we define and use a new model attribute, herein termed NM, to differentiate between gas- and water-bearing formations for each class of AVO anomaly found in this province. This new method was successfully tested in many areas in the Nile Delta Basin, where it has helped to identify subtle anomalies and thereby open the gate for further exploration activities in the area.
Predicting Perceived Naturalness of Human Animations Based on Generative Movement Primitive Models
Authors: Knopp Benjamin , Velychko Dmytro , Dreibrodt Johannes , Endres Dominik
Published: September 2019

We compared the perceptual validity of human avatar walking animations driven by six different representations of human movement using a graphics Turing test. All six representations are based on movement primitives (MPs), which are predictive models of full-body movement that differ in their complexity and prediction mechanism. Assuming that humans are experts at perceiving biological movement from noisy sensory signals, it follows that these percepts should be describable by a suitably constructed Bayesian ideal observer model. We build such models from MPs and investigate if the perceived naturalness of human animations are predictable from approximate Bayesian model scores of the MPs. We found that certain MP-based representations are capable of producing movements that are perceptually indistinguishable from natural movements. Furthermore, approximate Bayesian model scores of these representations can be used to predict perceived naturalness. In particular, we could show that movement dynamics are more important for perceived naturalness of human animations than single frame poses. This indicates that perception of human animations is highly sensitive to their temporal coherence. More generally, our results add evidence for a shared MP-representation of action and perception. Even though the motivation of our work is primarily drawn from neuroscience, we expect that our results will be applicable in virtual and augmented reality settings, when perceptually plausible human avatar movements are required.
Predictive Signatures Inform the Effective Repurposing of Decitabine to Treat KRAS–Dependent Pancreatic Ductal Adenocarcinoma
Authors: Mottini Carla , Tomihara Hideo , Carrella Diego , Lamolinara Alessia , Iezzi Manuela , Huang Justin K. , Amoreo Carla A. , Buglioni Simonetta , Manni Isabella , Robinson Frederick S. , Minelli Rosalba , Kang Ya'an , Fleming Jason B. , Kim Michael P. , Bristow Christopher A. , Trisciuoglio Daniela , Iuliano Antonella , Del Bufalo Donatella , Di Bernardo Diego , Melisi Davide , Draetta Giulio F. , Ciliberto Gennaro , Carugo Alessandro , Cardone Luca
Published: September 2019

Mutated KRAS protein is a pivotal tumor driver in pancreatic cancer. However, despite comprehensive efforts, effective therapeutics that can target oncogenic KRAS are still under investigation or awaiting clinical approval. Using a specific KRAS–dependent gene signature, we implemented a computer-assisted inspection of a drug–gene network to in silico repurpose drugs that work like inhibitors of oncogenic KRAS. We identified and validated decitabine, an FDA-approved drug, as a potent inhibitor of growth in pancreatic cancer cells and patient-derived xenograft models that showed KRAS dependency. Mechanistically, decitabine efficacy was linked to KRAS–driven dependency on nucleotide metabolism and its ability to specifically impair pyrimidine biosynthesis in KRAS–dependent tumors cells. These findings also showed that gene signatures related to KRAS dependency might be prospectively used to inform on decitabine sensitivity in a selected subset of patients with KRAS–mutated pancreatic cancer. Overall, the repurposing of decitabine emerged as an intriguing option for treating pancreatic tumors that are addicted to mutant KRAS, thus offering opportunities for improving the arsenal of therapeutics for this extremely deadly disease.

Significance:

Decitabine is a promising drug for cancer cells dependent on RAS signaling.
Germline BRCA-Associated Endometrial Carcinoma Is a Distinct Clinicopathologic Entity
Authors: de Jonge Marthe M. , Ritterhouse Lauren L. , de Kroon Cornelis D. , Vreeswijk Maaike P.G. , Segal Jeremy P. , Puranik Rutika , Hollema Harry , Rookus Matti A. , van Asperen Christi J. , van Leeuwen Flora E. , Smit Vincent T.H.B.M. , Howitt Brooke E. , Bosse Tjalling
Published: September 2019

Purpose:

Whether endometrial carcinoma (EC) should be considered part of the gBRCA1/2-associated hereditary breast and ovarian cancer (HBOC) syndrome is topic of debate. We sought to assess whether ECs occurring in gBRCA carriers are enriched for clinicopathologic and molecular characteristics, thereby supporting a causal relationship.

Experimental Design:

Thirty-eight gBRCA carriers that developed EC were selected from the nationwide cohort study on hereditary breast and ovarian cancer in the Netherlands (HEBON), and these were supplemented with four institutional cases. Tumor tissue was retrieved via PALGA (Dutch Pathology Registry). Nineteen morphologic features were scored and histotype was determined by three expert gynecologic pathologists, blinded for molecular analyses (UCM-OncoPlus Assay including 1213 genes). ECs with LOH of the gBRCA-wild-type allele (gBRCA/LOHpos) were defined “gBRCA-associated,” those without LOH (gBRCA/LOHneg) were defined “sporadic.”

Results:

LOH could be assessed for 40 ECs (30 gBRCA1, 10 gBRCA2), of which 60% were gBRCA/LOHpos. gBRCA/LOHpos ECs were more frequently of nonendometrioid (58%, P = 0.001) and grade 3 histology (79%, P < 0.001). All but two were in the TP53-mutated TCGA-subgroup (91.7%, P < 0.001). In contrast, gBRCA/LOHneg ECs were mainly grade 1 endometrioid EC (94%) and showed a more heterogeneous distribution of TCGA-molecular subgroups: POLE-mutated (6.3%), MSI-high (25%), NSMP (62.5%), and TP53-mutated (6.3%).

Conclusions:

We provide novel evidence in favor of EC being part of the gBRCA-associated HBOC-syndrome. gBRCA-associated ECs are enriched for EC subtypes associated with unfavorable clinical outcome. These findings have profound therapeutic consequences as these patients may benefit from treatment strategies such as PARP inhibitors. In addition, it should influence counseling and surveillance of gBRCA carriers.
Identification of Resistance Pathways Specific to Malignancy Using Organoid Models of Pancreatic Cancer
Authors: Ponz-Sarvise Mariano , Corbo Vincenzo , Tiriac Hervé , Engle Dannielle D. , Frese Kristopher K. , Oni Tobiloba E. , Hwang Chang-Il , Öhlund Daniel , Chio Iok In Christine , Baker Lindsey A. , Filippini Dea , Wright Kevin , Bapiro Tashinga E. , Huang Pearl , Smith Paul , Yu Kenneth H. , Jodrell Duncan I. , Park Youngkyu , Tuveson David A.
Published: September 2019

Purpose:

KRAS is mutated in the majority of pancreatic ductal adenocarcinoma. MAPK and PI3K-AKT are primary KRAS effector pathways, but combined MAPK and PI3K inhibition has not been demonstrated to be clinically effective to date. We explore the resistance mechanisms uniquely employed by malignant cells.

Experimental Design:

We evaluated the expression and activation of receptor tyrosine kinases in response to combined MEK and AKT inhibition in KPC mice and pancreatic ductal organoids. In addition, we sought to determine the therapeutic efficacy of targeting resistance pathways induced by MEK and AKT inhibition in order to identify malignant-specific vulnerabilities.

Results:

Combined MEK and AKT inhibition modestly extended the survival of KPC mice and increased Egfr and ErbB2 phosphorylation levels. Tumor organoids, but not their normal counterparts, exhibited elevated phosphorylation of ERBB2 and ERBB3 after MEK and AKT blockade. A pan-ERBB inhibitor synergized with MEK and AKT blockade in human PDA organoids, whereas this was not observed for the EGFR inhibitor erlotinib. Combined MEK and ERBB inhibitor treatment of human organoid orthotopic xenografts was sufficient to cause tumor regression in short-term intervention studies.

Conclusions:

Analyses of normal and tumor pancreatic organoids revealed the importance of ERBB activation during MEK and AKT blockade primarily in the malignant cultures. The lack of ERBB hyperactivation in normal organoids suggests a larger therapeutic index. In our models, pan-ERBB inhibition was synergistic with dual inhibition of MEK and AKT, and the combination of a pan-ERBB inhibitor with MEK antagonists showed the highest activity both in vitro and in vivo.
Quantification of Motor Function in Huntington Disease Patients Using Wearable Sensor Devices
Authors: Gordon Mark Forrest , Grachev Igor D. , Mazeh Itzik , Dolan Yonatan , Reilmann Ralf , Loupe Pippa S. , Fine Shai , Navon-Perry Leehee , Gross Nicholas , Papapetropoulos Spyros , Savola Juha-Matti , Hayden Michael R.
Published: September 2019

Previous studies have demonstrated the feasibility and promise of wearable sensors as objective measures of motor impairment in Parkinson disease and essential tremor. However, there are few published studies that have examined such an application in Huntington disease (HD). This report provides an evaluation of the potential to objectively quantify chorea in HD patients using wearable sensor data. Data were derived from a substudy of the phase 2 Open-PRIDE-HD study, where 17 patients were screened and 15 patients enrolled in the substudy and ultimately 10 patients provided sufficient wearable sensor data. The substudy was designed to provide high-resolution data to inform design of predictive algorithms for chorea quantification. During the entire course of the 6-month study, in addition to chorea ratings from 18 in-clinic assessments, 890 home assessments, and 1,388 responses to daily reminders, 33,000 h of high-resolution accelerometer data were captured continuously from wearable smartwatches and smartphones. Despite its limited sample size, our study demonstrates that arm chorea can be characterized using accelerometer data during static assessments. Nonetheless, the small sample size limits the generalizability of the model. The sensor-based model can quantify the chorea level with high correlation to the chorea severity reported by both clinicians and patients. In addition, our analysis shows that the chorea digital signature varies between patients. This work suggests that digital wearable sensors have the potential to support clinical development of medications in patients with movement disorders, such as chorea. However, additional data would be needed from a larger number of HD patients with a full range of chorea severity (none to severe) with and without intervention to validate this potentially predictive technology.
Blended Psychotherapy – verzahnte Psychotherapie: Behandlungskonzept und Fallbericht zur Integration von Internet- und Mobil-basierten Interventionen in die Kurzzeittherapie von depressiven Störungen
Authors: Titzler Ingrid , Egle Viktoria , Berking Matthias , Gumbmann Corinna , Ebert David Daniel
Published: September 2019

Hintergrund: Blended Psychotherapy (bPT) ist ein Behandlungskonzept zur Integration von Internet-/Mobil-basierten Interventionen in die ambulante/stationäre Psychotherapie. Es kann den Therapieprozess bereichern, indem Online-basierte Behandlungselemente als verlängerter therapeutischer Arm genutzt und zwischen den Therapiesitzungen von PatientInnen zeit- und ortsunabhängig bearbeitet werden. Dadurch könnten die Effektivität von Psychotherapie potenziell verbessert oder mehr Therapieplätze durch die eingesparte Therapeutenzeit angeboten werden. Der Fallbericht soll ein Verständnis der Verzahnung der Behandlungselemente ermöglichen. Fallbericht: Die viermonatige Kurzzeit-Depressionsbehandlung einer 48-jährigen Patientin mit sechs Face-to-Face-Therapiesitzungen, sechs Online-Lektionen und App-Ratings wird nach den CARE-Richtlinien und auf Basis quantitativer und qualitativer Daten (Behandlungsdokumentation) dargestellt. Die depressive Sympto­matik reduzierte sich im Behandlungsverlauf klinisch signifikant (Patient Health Questionnaire [PHQ-9], 0–27: T0 = 17; T1 = 7) von einer mittel-schwergradigen zu einer subklinisch-milden Ausprägung und erfüllte im 12-Monats-Diagnostikinterview keine klinischen Diagnosekriterien. Die Patientin zeigte eine maximale Behandlungszufriedenheit (Fragebogen zur Patientenzufriedenheit [ZUF-8], 8–32: T1 = 32) sowie Adhärenz und bewertete die therapeutische Bezie­hung sehr positiv (Working Alliance Inventory [WAI], 12–60: T1 = 57). Schlussfolgerung: bPT war bei dieser Patientin ge­eignet, um depressive Symptome zu reduzieren. Stärken der Behandlung waren die gute Integrierbarkeit der Online-Behandlung in die Berufstätigkeit der Patientin und die Individualisierung in den Therapiegesprächen durch die Therapeutin. Die Vorgabe von sechs Therapiesitzungen schränkte den Behandlungserfolg insofern ein, dass nicht alle Behandlungsthemen therapeutisch bearbeitet und keine Rezidiv­prophylaxe durchgeführt werden konnten.