bluuebunny/crossref_metadata_2025 huggingface dataset:
SUITABILITY OF CURRENT EVALUATION FRAMEWORKS FOR USE IN THE HEALTH TECHNOLOGY ASSESSMENT OF MOBILE MEDICAL APPLICATIONS: A SYSTEMATIC REVIEW
Authors: Moshi Magdalena Ruth , Tooher Rebecca , Merlin Tracy
Published: September 2018

Objectives:

To identify and appraise existing evaluation frameworks for mobile medical applications (MMA) and determine their suitability for use in health technology assessment (HTA) of these technologies.

Methods:

Systematic searches were conducted of seven bibliographic databases to identify literature published between 2008 and 2016 on MMA evaluation frameworks. Frameworks were eligible if they were used to evaluate at least one of the HTA domains of effectiveness, safety, and/or cost and cost-effectiveness of an MMA. After inclusion, the frameworks were reviewed to determine the number and extent to which other elements of an HTA were addressed by the framework.

Results:

A total of forty-five frameworks were identified that assessed MMAs. All frameworks assessed whether the app was effective. Of the thirty-four frameworks that examined safety, only seven overtly evaluated potential harms from the MMA (e.g., the impact of inaccurate information). Only one framework explicitly considered a comparator. Technology specific domains were sporadically addressed.

Conclusion:

None of the evaluation frameworks could be used, unaltered, to guide the HTA of MMAs. To use these frameworks in HTA they would need to identify relevant comparators, improve assessments of harms and consider the ongoing effect of software updates on the safety and effectiveness of MMAs. Attention should also be paid to ethical issues, such as data privacy, and technology specific characteristics. Implications: Existing MMA evaluation frameworks are not suitable for use in HTA. Further research is needed before an MMA evaluation framework can be developed that will adequately inform policy makers.
The metrical parse is guided by gradient phonotactics
Authors: Olejarczuk Paul , Kapatsinski Vsevolod
Published: September 2018

Phonotactic generalisations can be computed at different levels of granularity, from a coarse-grained legal/illegal dichotomy (blick,dwick≻ *bnick, *lbick) to a fine-grained gradient of acceptability (blick≻dwick≻bnick≻lbick). This article investigates the sensitivity of the English metrical parse to the granularity of medial onset phonotactics. We present two experiments that feature pseudo-words with medial consonants and CC clusters varying in word-edge frequency and sonority (e.g.vatablick,vatadwick,vatabnick,vatalbick). The metrical parse is inferred from a hyphenation experiment and an online stress-assignment experiment. The results of both studies indicate that the parse is stochastic, and guided by relatively fine-grained phonotactic dependencies. Vocabulary simulations suggest that this level of granularity may arise because the gradient parser consistently outperforms the coarse-grained alternative across the developing lexicon.
Dual band- dual polarized planar inverted F-antenna for MBAN applications
Authors: Bhattacharjee Shankar , Midya Manas , Mitra Monojit , Bhadra Chaudhuri S.R.
Published: September 2018

A planar inverted F-Antenna with the dual band-dual polarization property is presented for medical body area networks applications. The designed antenna covers the 2.45 GHz industrial, scientific and medical, 4 G long term evolution (2.5–2.69 GHz) bands for ON body communication and Wi-Fi and WLAN (3.5–3.6 GHz) bands for OFF body communication. At the lower band, an equivalent offset fed magnetic microstrip type dipole has been utilized that generate field parallel to the surface of the body for supporting ON body communication. The broadside radiation pattern has been realized using the slotted patch counterpart for supporting OFF body communication. This technique has resulted in a design of dual band dual mode property using a single radiator. The footprint of the antenna is only 0.35λg × 0.17λg × 0.08λg. Owing to its compactness, lightweight, and easy mountable property (due to foam substrate), the proposed antenna is found to be robust for MBAN applications. The maximum permissible transmitted power for the 1st band is 25.78 and 20.3 dBm for the 2nd one to maintain standard specific absorption rate limitations of 1.6 W/Kg. Experimental investigations over human body showed minimal deviations from the free space conditions which makes it a potential candidate for body-centric communications.
Recover recovery style from psychosis: a psychometric evaluation of the German version of the Recovery Style Questionnaire (RSQ)
Authors: Gruber M. , Rumpold T. , Schrank B. , Sibitz I. , Otzelberger B. , Jahn R. , Amering M. , Unger A.
Published: September 2018

Aims

The way an individual handles the experience of psychosis, the so-called ‘recovery style’, has been shown to substantially affect long-term outcomes. The Recovery Style Questionnaire (RSQ) measures this psychological dimension. The aim of this study was to provide a validation of the German version of the RSQ and to raise awareness for recovery-oriented approaches.

Methods

The RSQ was translated into German according to the guidelines of the WHO and patients were administered this questionnaire and measures of internalised stigma, psychotic symptoms, illness concept, empowerment, self-esteem and quality of life. Descriptive statistics were demonstrated to characterise the sample. Reliability was assessed in different forms: internal consistency, test–retest reliability and split-half reliability. Items were evaluated with descriptive data and item-total correlations. Convergent and discriminant validity were shown, and a confirmatory factor analysis was performed. In order to ameliorate the model, a post hoc model modification was done.

Results

The sample consisted of 138 patients diagnosed with schizophrenia spectrum disorders (mean age: 35.7 years; 53.6% men; mean duration of illness: 20.6 years) with a mean RSQ overall percentage of 66.12 (s.d. ± 17.43%), mainly representing the categories ‘mixed picture’ and ‘tends towards integration’. The reliability of the RSQ was acceptable with a Cronbach's α of 0.741 and a test–retest coefficient of 0.502. Item-total correlations were not acceptable for 27 of 39 items. Moderate evidence for convergent validity of the RSQ was found. Confirmatory factor analysis revealed that the 13-factor model with 39 items originally proposed was partially poorly replicated in the present sample (χ2 ratio to degrees of freedom (χ2/df) of 1.732, Comparative Fit Index (CFI) of 0.585, Normed Fit Index (NFI) of 0.414, Tucker–Lewis Index (TLI) of 0.508, root mean square error of approximation (RMSEA) of 0.095). The RSQ was modified based on item-total correlations and path coefficients of the single items. The confirmatory factor analysis of the resulting one-factor model with 11 items showed adequate fit to the data (χ2/df of 1.562, CFI of 0.936, NFI of 0.847, TLI of 0.910, RMSEA of 0.083) and demonstrated good model fit.

Conclusions

Despite partially insufficient psychometric data of the original RSQ, the concept of recovery style is beneficial to psychiatric research and clinical practice. The underlying idea is valuable, and the questionnaire needs further development. Therefore, a short version of the RSQ is proposed.
Thromboembolic disease in females and males aged 10 to 39 years in Germany
Authors: von Beckerath Olga , Santosa Frans , Waldhausen Rolf , Moerchel Christian , Kröger Knut
Published: September 2018

Abstract. Background: We analysed differences in hospitalization rates for venous diseases such as pulmonary embolism (PE), deep vein thrombosis (DVT), sinus vein thrombosis (SVT), portal vein thrombosis (PVT), and Budd-Chiari syndrome (BCS) as well as for arterial diseases such as myocardial infarction (MI) and embolic stroke (ES) in females and males aged 10 to 39 years. Patients and methods: Detailed lists of hospitalizations with the principal and additional diagnoses for PE (ICD-code I26.0 + I26.9), DVT (I80.0–I80.9), SVT (I67.6), PVT (I81), BCS (I82.0), MI (I21.0–I21.9), and ES (I63.1 + I63.4) in males and females aged 10 to 39 years in the years 2006 to 2015 were provided by the Federal Statistical Office in Germany. Results: Considering the 10-year period there were more female than male cases hospitalized with the principal diagnoses for PE, DVT, SVT, and BCS. Looking at the principal diagnosis of the year 2015, one can see a steep increase in numbers of hospitalization for PE, DVT, and SVT in females ranging from the ages 12 to 13 and 14 to 15 years compared to males. The curves of PE and DVT meet again in the age group between 32 and 33 years, but not for SVT. The greatest differences are seen at the end of the second and at the beginning of the third decade of life. In contrast, MI was more frequent in young males beginning at the age of 18 to 19 years. The number of female and male cases with ES and PVT were almost similar in the different age groups. Conclusions: The presented data show higher hospitalization rates for females in the age group 10 to 39 years for different venous thrombosis but not for MI and ES.
Generation of Lower L Shell Dayside Chorus by Energetic Electrons From the Plasma Sheet
Authors: He Yihua , Xiao Fuliang , Su Zhenpeng , Zheng Huinan , Yang Chang , Liu Si , Zhou Qinghua
Published: September 2018

Currently, the generation mechanism for the lower L shell dayside chorus has still remained an open question. Here we report two storm events: 6–7 March 2016 and 20–21 January 2016, when Van Allen Probes observed enhanced dayside chorus with lower and higher wave normal angles (the angles between the wave vector and the geomagnetic field) in the region of L = 3.5–6.3 and MLT = 5.6–13.5. Hot and energetic (∼ 1–100 keV) electrons displayed enhancements in fluxes and anisotropy when they were injected from the plasma sheet and drifted from midnight through dawn toward the dayside. Calculations of chorus local growth rates under different waves normal angles show that the upper cutoff and peak wave frequencies display similar patterns to the observations. Chorus growth rates maximize for the parallel propagation and drop with increasing wave normal angles. The current results confirm that the observed lower L shell dayside chorus can be excited by anisotropic electrons originating from the plasma sheet in drifting from the nightside to the dayside.
Extremely Energetic Rockfalls
Authors: De Blasio Fabio Vittorio , Dattola Giuseppe , Crosta Giovanni Battista
Published: September 2018

Extremely energetic rockfalls (EERs) are defined here as rockfalls for which a combination of both large volume and free fall height of hundreds of meters results in energy larger than about 80 GJ released in a short time. Examples include several events worldwide. In contrast to low energy rockfalls where block disintegration is limited, in EERs the impact after free fall causes immediate release of energy much like an explosion. The resulting air blast can snap trees hundreds of meters ahead of the fall area. Pulverized rock at high speed can abrade vegetation in a process of sandblasting, and particles suspended by the blast and the subsequent debris cloud may travel farther than the impact zone, blanketing vast areas. Using published accounts and new data, we introduce physically based models formulated on analogies with explosions and explosive fragmentation to describe EERs. Results indicate that a portion of the initial potential energy of the block is spent in rock disintegration at impact (typically 0.2%–18%), while other sources of energy loss (air drag, seismic, sound, and ground deformation) are negligible; consequently, more than 80% of the potential energy is converted to kinetic energy of the fragmented block (ballistic projection, shock wave, sand blast, and dust cloud). We also propose simple estimates for the flow of the dust cloud associated with an EER and its long settling time. The areal extent of the affected zone is estimated from the energy balance and an empirical power law relationship.
Toward Robust Interpretation of Low‐Temperature Thermochronometers in Magmatic Terranes
Authors: Murray Kendra E. , Braun Jean , Reiners Peter W.
Published: September 2018

Many regions central to our understanding of tectonics and landscape evolution are active or ancient magmatic terranes, and robust interpretation of low‐temperature thermochronologic ages in these settings requires careful attention to the drivers of rock heating and cooling, including magmatism. However, we currently lack a quantitative framework for evaluating the potential role of magmatic cooling—that is, post‐magmatic thermal relaxation—in shaping cooling age patterns in regions with a history of intrusive magmatism. Here we use analytical approximations and numerical models to characterize how low‐temperature thermochronometers document cooling inside and around plutons in steadily exhuming environments. Our models predict that the thermal field a pluton intrudes into, specifically the ambient temperatures relative to the closure temperature of a given thermochronometer, is as important as the pluton size and temperature in controlling the pattern and extent of thermochronometer resetting in the country rocks around a pluton. We identify one advective and several conductive timescales that govern the relationship between the crystallization and cooling ages inside a pluton. In synthetic vertical age‐elevation relationships (AERs), resetting next to plutons results in changes in AER slope that could be misinterpreted as past changes in exhumation rate if the history of magmatism is not accounted for. Finally, we find that large midcrustal plutons, such as those emplaced at ~10–15‐km depth, can reset the low‐temperature thermochronometers far above them in the upper crust—a result with considerable consequences for thermochronology in arcs and regions with a history of magmatic activity that may not have a surface expression.
Quartz Solubility in the Two‐Phase Region of the NaCl‐H2O System: An Experimental Study With Application to the Piccard Hydrothermal Field, Mid‐Cayman Rise
Authors: Scheuermann Peter P. , Tan Chunyang , Seyfried William E.
Published: September 2018

Hydrothermal experiments were performed at elevated temperature (420–500 °C) and pressure (31.0–51.0 MPa) in the NaCl‐H2O system to measure quartz solubility in coexisting vapor and liquid and extend the calibrated range of the Si‐Cl geothermobarometer. In the vapor, the density‐based equations for quartz solubility of Fournier (1983, http://doi.org/10.1016/0016‐7037(83)90279‐X) and Von Damm et al. (1991, http://doi.org/10.2475/ajs.291.10.977) agree well with the experimental data, while the equation of Fournier (1983) also accurately predicts SiO2(aq) concentrations in the liquid. Importantly, the equations of Fournier (1983) and Von Damm et al. (1991) were calibrated based on quartz solubility in single phase fluids (no coexisting vapor‐liquid) at higher pressure than investigated here. The new experimental data therefore extend the pressure range of the density‐equations and demonstrate that quartz solubility in either vapor or liquid can be treated independently as a function of temperature, pressure, and fluid density. The Si‐Cl geothermobarometer indicates that fluids venting from Piccard reach 540 ± 15 °C, 62.5 ± 3.0 MPa. These are the hottest and deepest conditions yet recorded by an actively venting seafloor hydrothermal fluid. Based on the calculated enthalpy differences between the subsurface fluid and that venting at the seafloor, approximately one third of the heat extracted at depth is lost during conductive cooling of the hydrothermal fluid. Incorporating the heat lost during conductive cooling into the overall budget at Piccard yields a flux of 100 ± 37 MW and an associated hydrothermal fluid flux of 1.2 ± 0.4 × 109 kg/year. The newly calibrated Si‐Cl geothermobarometer provides important constraints for accurate determination of heat and mass fluxes at axial vent sites.
A Generalized Approach to Estimating Diffusion Length of Stable Water Isotopes From Ice‐Core Data
Authors: Kahle Emma C. , Holme Christian , Jones Tyler R. , Gkinis Vasileios , Steig Eric J.
Published: September 2018

Diffusion of water vapor in the porous firn layer of ice sheets damps high‐frequency variations in water‐isotope profiles. Through spectral analysis, the amount of diffusion can be quantified as the“diffusion length,” the mean cumulative diffusive displacement of water molecules relative to their original location at time of deposition. In this study, we use two types of ice‐core data, obtained from either continuous‐flow analysis or discrete sampling, to separate diffusional effects occurring in the ice sheet from those arising through analytical processes in the laboratory. In both Greenlandic and Antarctic ice cores, some characteristics of the power spectral density of a data set depend on the water‐isotope measurement process. Due to these spectral characteristics, currently established approaches for diffusion estimation do not work equally well for newer, continuously measured data sets with lower instrument noise levels. We show how smoothing within the continuous‐flow analysis system can explain these spectral differences. We propose two new diffusion‐estimation techniques, which can be applied to either continuously or discretely measured data sets. We evaluate these techniques and demonstrate their viability for future use. The results of this study have the potential to improve climate interpretation of ice‐core records as well as models of firn densification and diffusion.
HDAC6 inhibitor TST strengthens the antiproliferative effects of PI3K/mTOR inhibitor BEZ235 in breast cancer cells via suppressing RTK activation
Authors: Sun Shixiu , Zhang Yujie , Zheng Jianchao , Duan Biao , Cui Jie , Chen Yan , Deng Wenjie , Ye Bixing , Liu Lei , Chen Yongchang , Du Jun , Gu Luo
Published: September 2018

NVP-BEZ235 (BEZ235), an available dual PI3K/mTOR inhibitor, showed antitumor effect and provided a therapy strategy in carcinomas. However, the acquired upregulation of multiple receptor tyrosine kinases (RTKs) by NVP-BEZ235 in tumors limits its clinical efficacy. HDAC6, a class II histone deacetylase, is associated with expressions of multiple RTKs. The aim of this study was to detect whether co-treatment with HDAC6 inhibitor Tubastatin A (TST) would enhance the anticancer effects of BEZ235 in breast cancer cells. In this study, we described that treatment of breast cancer cell lines (T47D, BT474, and MDA-MB-468) with BEZ235 significantly triggered PI3K/mTOR signaling inactivation and increased multiple RTK expression, including EGFR, HER2, HER3, IGF-1 receptor, insulin receptor, and their phosphorylation levels. The adding of TST destabilized these RTKs in those breast cancer cells. Co-treatment with BEZ235 and TST reduced cell proliferative rate by strengthening Akt inactivation. In addition, the combination of these two drugs also cooperatively arrested cell cycle and DNA synthesis. In conclusion, the co-treatment with PI3K/mTOR inhibitor BEZ235 and HDAC6 inhibitor TST displayed additive antiproliferative effects on breast cancer cells through inactivating RTKs and established a rationable combination therapy to treat breast cancer.
Melanoma cells resistant towards MAPK inhibitors exhibit reduced TAp73 expression mediating enhanced sensitivity to platinum-based drugs
Authors: Makino Elena , Gutmann Vanessa , Kosnopfel Corinna , Niessner Heike , Forschner Andrea , Garbe Claus , Sinnberg Tobias , Schittek Birgit
Published: September 2018

The efficacy of targeted MAPK signalling pathway inhibitors (MAPKi) in metastatic melanoma therapy is limited by the development of resistance mechanisms that results in disease relapse. This situation still requires treatment alternatives for melanoma patients with acquired resistance to targeted therapy. We found that melanoma cells, which developed resistance towards MAPKi show an enhanced susceptibility to platinum-based drugs, such as cisplatin and carboplatin. We found that this enhanced susceptibility inversely correlates with the expression level of the p53 family member TAp73. We show that the lower expression of the TAp73 isoform in MAPKi-resistant melanoma cells enhances accumulation of DNA double-strand breaks upon cisplatin and carboplatin treatment by reducing the efficiency of nucleotide excision repair. These data suggest that a subgroup of melanoma patients with acquired resistance to MAPKi treatment and low TAp73 expression can benefit from chemotherapy with platinum-based drugs as a second-line therapy.
Regulation of cell surface protease receptor S100A10 by retinoic acid therapy in acute promyelocytic leukemia (APL)☆
Authors: Holloway Ryan W. , Thomas Margaret L. , Cohen Alejandro M. , Bharadwaj Alamelu G. , Rahman Mushfiqur , Marcato Paola , Marignani Paola A. , Waisman David M.
Published: September 2018

S100A10 (p11), a member of the S100 family of small dimeric EF-hand-type Ca2+-binding proteins, plays a role in a variety of both intracellular and extracellular processes. Previous studies have suggested that p11 is intrinsically unstable and requires binding to annexin A2 (p36) to prevent its rapid ubiquitylation and degradation. Our laboratory has shown that p11 levels are stimulated by the expression of the oncoprotein, PML/RARα. Furthermore, treatment of the APL cell line, NB4 with all-trans retinoic acid (ATRA) causes the rapid loss of p36 and p11 protein. However, the mechanism by which ATRA regulates p11 levels has not been established. Here, we show that the proteasomal inhibitor, lactacystin reversed the ATRA-dependent loss of p11, but did not cause an accumulation of ubiquitylated forms of p11, suggesting that ATRA promotes the proteasomal degradation of p11 in an ubiquitin-independent manner. ATRA treatment of MCF-7 breast cancer cells reduced p11 but not p36 transcript and protein levels, thus indicating that ATRA can regulate p11 levels independently of PML/RARα and p36. Overexpression of p36 upregulated p11 protein but not mRNA levels, indicating that p36 affects p11 post translationally. The forced expression of ubiquitin and p11 in 293 T cells resulted in ubiquitylation of p11 that was blocked by mutagenesis of lysine 57. This study highlights the complex regulation of p11 by retinoid signaling and challenges the hypothesis that ubiquitin-mediated proteasomal degradation of p11 represents a universal mechanism of regulation of this protein.
KLLN-mediated DNA damage-induced apoptosis is associated with regulation of p53 phosphorylation and acetylation in breast cancer cells
Authors: Sankunny Madhav , Eng Charis
Published: September 2018

KLLN is a target of p53 involved in S-phase cell cycle regulation deemed necessary and sufficient for p53-mediated apoptosis. Germline promoter hypermethylation of KLLN is associated with a cancer-predisposition syndrome, Cowden syndrome. KLLN’s DNA-binding ability is associated with transcription regulation and maintenance of genomic stability. Here, we report on KLLN’s role in DNA damage response (DDR) mediated through apoptosis in breast cells with and without a cancer phenotype. KLLN expression was upregulated after doxorubicin-induced DNA damage and this upregulation can be abrogated using RNAi-mediated gene silencing. Silencing KLLN after doxorubicin treatment effected DDR shown by decreased γ-H2AX foci and expression, and apoptosis assessed by decreased frequency of apoptotic nuclei and decreased expression of definitive markers of apoptosis. Contrary to expectations, there was no change in cell cycle regulation after KLLN silencing. These results were observed in breast cells with wildtype and mutant p53. At early timepoints after doxorubicin treatment, knocking down KLLN resulted in decreased Ser15-phosphorylation of p53 but not Thr68-phosphorylation of CHK2 or the phosphorylation of upstream regulators such as ATM and ATR. Interestingly, a second pathway for p53 activation was also affected by knockdown of KLLN. After doxorubicin treatment, Thr454-phosphorylation of DBC1, required to inhibit deacetylation of p53 by SIRT1, was decreased and therefore acetylation of p53 was also decreased with KLLN knockdown. Therefore, our observations suggest that KLLN’s role in DNA damage-induced apoptosis is likely independent of p53 and is associated with a two-pronged regulation of p53 activation.
BTK modulates p73 activity to induce apoptosis independently of p53
Authors: Rada Miran , Barlev Nickolai , Macip Salvador
Published: September 2018

Bruton’s tyrosine kinase (BTK) is a key component of B cell receptor signalling. Because of this, BTK plays an important role in cell proliferation and survival in various B cell malignancies. However, in certain contexts, BTK can also have tumour suppressor functions. We have previously shown that BTK activates the p53 transcriptional activity by binding to and phosphorylating p53, as well as acting on MDM2 to reduce its inhibitory effects. This results in increased p53 functions, including enhanced cell death. Here, we report that BTK can also induce cell death and increase responses to DNA damage independently of p53. This is concomitant to the induction of p21, PUMA and MDM2, which are classic target genes of the p53 family of proteins. Our results show that these p53-independent effects of BTK are mediated through p73. Similar to what we observed in the p53 pathway, BTK can upregulate p73 after DNA damage and induce expression of its target genes, suggesting that BTK is a modulator of p73 functions and in the absence of p53. This effect allows BTK to have pro-apoptotic functions independently of its effects on the p53 pathway and thus play an important role in the DNA damage-related induction of apoptosis in the absence of p53. This provides a novel role of BTK in tumour suppression and contributes to the understanding of its complex pleiotropic functions
ADRB2 polymorphism Arg16Gly modifies the natural outcome of heart failure and dictates therapeutic response to β-blockers in patients with heart failure
Authors: Huang Jin , Li Chenze , Song Ying , Fan Xiaohan , You Ling , Tan Lun , Xiao Lei , Li Qing , Ruan Guoran , Hu Senlin , Cui Wei , Li Zongzhe , Ni Li , Chen Chen , Woo Anthony Yiu-Ho , Xiao Rui-Ping , Wang Dao Wen
Published: September 2018

We sought to investigate the association of single nucleotide polymorphisms (SNPs) of the genes involved in βAR signaling with the response of patients to βAR blockers. A total of 2403 hospitalized patients with chronic heart failure (HF) were enrolled in a multicenter observational study as the first cohort and followed up for a mean period of 20 months. Genes for β1AR, β2AR, and the major cardiac G-protein-coupled receptor kinases (GRKs) GRK2 and GRK5 were analyzed to identify SNPs, and patients were stratified according to genotypes. A second independent cohort enrolling 919 patients with chronic HF was applied to validate the observed associations. The signaling properties of the key identified SNPs were assessed in vitro. Our data showed that HF patients harboring the Gly16 allele in the gene for β2AR (ADRB2) had an increased risk of the composite end point relative to patients who were homozygous for Arg16. Notably, these patients showed a beneficial response to βAR-blocker treatment in a G allele-dose-dependent manner, whereas Arg16 homozygotes had no response to βAR-blocker therapy. This Arg16Gly genotype-dependent heterogeneity in clinical outcomes of HF was successfully validated in the second independent population. Besides, the in vitro experiments revealed that G allele carriers were defective in β2AR-coupled inhibitory adenylate cyclase g (Gi) protein signaling.
A plant Bro1 domain protein BRAF regulates multivesicular body biogenesis and membrane protein homeostasis
Authors: Shen Jinbo , Zhao Qiong , Wang Xiangfeng , Gao Caiji , Zhu Ying , Zeng Yonglun , Jiang Liwen
Published: September 2018

Plant development, defense, and many physiological processes rely on the endosomal sorting complex required for transport (ESCRT) machinery to control the homeostasis of membrane proteins by selective vacuolar degradation. Although ESCRT core components are conserved among higher eukaryotes, the regulators that control the function of the ESCRT machinery remain elusive. We recently identified a plant-specific ESCRT component, FREE1, that is essential for multivesicular body/prevacuolar compartment (MVB/PVC) biogenesis and vacuolar sorting of membrane proteins. Here we identify a plant-specific Bro1-domain protein BRAF, which regulates FREE1 recruitment to the MVB/PVC membrane by competitively binding to the ESCRT-I component Vps23. Altogether, we have successfully identified a role for BRAF, whose function as a unique evolutionary ESCRT regulator in orchestrating intraluminal vesicle formation in MVB/PVCs and the sorting of membrane proteins for degradation in plants makes it an important regulatory mechanism underlying the ESCRT machinery in higher eukaryotes.
14-3-3 proteins activate Pseudomonas exotoxins-S and -T by chaperoning a hydrophobic surface
Authors: Karlberg Tobias , Hornyak Peter , Pinto Ana Filipa , Milanova Stefina , Ebrahimi Mahsa , Lindberg Mikael , Püllen Nikolai , Nordström Axel , Löverli Elinor , Caraballo Rémi , Wong Emily V. , Näreoja Katja , Thorsell Ann-Gerd , Elofsson Mikael , De La Cruz Enrique M. , Björkegren Camilla , Schüler Herwig
Published: September 2018

Pseudomonas are a common cause of hospital-acquired infections that may be lethal. ADP-ribosyltransferase activities of Pseudomonas exotoxin-S and -T depend on 14-3-3 proteins inside the host cell. By binding in the 14-3-3 phosphopeptide binding groove, an amphipathic C-terminal helix of ExoS and ExoT has been thought to be crucial for their activation. However, crystal structures of the 14-3-3β:ExoS and -ExoT complexes presented here reveal an extensive hydrophobic interface that is sufficient for complex formation and toxin activation. We show that C-terminally truncated ExoS ADP-ribosyltransferase domain lacking the amphipathic binding motif is active when co-expressed with 14-3-3. Moreover, swapping the amphipathic C-terminus with a fragment from Vibrio Vis toxin creates a 14-3-3 independent toxin that ADP-ribosylates known ExoS targets. Finally, we show that 14-3-3 stabilizes ExoS against thermal aggregation. Together, this indicates that 14-3-3 proteins activate exotoxin ADP-ribosyltransferase domains by chaperoning their hydrophobic surfaces independently of the amphipathic C-terminal segment.
A spin torque meter with magnetic facet domains
Authors: Moon Kyoung-Woong , Kim Changsoo , Yoon Jungbum , Choi Jun Woo , Kim Dong-Ok , Song Kyung Mee , Kim Dongseuk , Chun Byong Sun , Hwang Chanyong
Published: September 2018

Current-induced magnetic domain wall (DW) motion is an important operating principle of spintronic devices. Injected current generates spin torques (STs) on the DWs in two ways. One is the spin transfer from magnetic domains to the walls by the current flowing in the magnet. Current flow in attached heavy metals also generates another ST because of the spin-Hall effect. Both phenomena explain the wall motions well; therefore, their respective contribution is an important issue. Here, we show the simultaneous measurement of both torques by using magnetic facet domains that form mountain-shaped domains with straight walls. When the STs and the external magnetic field push the walls in opposite directions, the walls should have equilibrium angles to create balanced states. Such angles can be modulated by an additional in-plane magnetic field. Angle measurements distinguish the STs because each torque has a distinct mechanism related to the DW structure.
Hydrogen spillover through Matryoshka-type (ZIFs@)n−1ZIFs nanocubes
Authors: Zhan Guowu , Zeng Hua Chun
Published: September 2018

Hydrogen spillover phenomenon is well-documented in hydrogenation catalysis but still highly disputed in hydrogen storage. Until now, the existence of hydrogen spillover through metal–organic frameworks (MOFs) remains a topic of ongoing debate and how far the split hydrogen atoms diffuse in such materials is unknown. Herein we provide experimental evidence of the occurrence of hydrogen spillover in microporous MOFs at elevated temperatures, and the penetration depths of atomic hydrogen were measured quantitatively. We have made Matryoshka-type (ZIFs@)n−1ZIFs (where ZIFs = ZIF-8 or ZIF-67) nanocubes, together with Pt nanoparticles loaded on their external surfaces to produce atomic hydrogen. Within the (ZIFs@)n−1ZIFs, the ZIF-8 shell served as a ruler to measure the travelling distance of H atoms while the ZIF-67 core as a terminator of H atoms. In addition to the hydrogenolysis at normal pressure, CO2 hydrogenation can also trace the migration of H atoms over the ZIF-8 at high pressure.
Publisher Correction: Quantum coherence of multiple excitons governs absorption cross-sections of PbS/CdS core/shell nanocrystals
Authors: Tahara Hirokazu , Sakamoto Masanori , Teranishi Toshiharu , Kanemitsu Yoshihiko
Published: September 2018

The original version of this Article contained an error in the seventh sentence of the second paragraph of the ‘TA amplitudes for double pump-pulse excitation” section of the Results, which incorrectly read ‘The absorption cross-sections of the transitions from the single exciton state to the biexciton and triexciton states are denoted by σ′ and σ'', respectively.’ The correct version states ‘σ′′’ in place of ‘σ''’.

The ninth and tenth sentences of the same paragraph originally incorrectly read ‘The most important issue of this work is to clarify whether the multiple exciton absorption cross-sections σ′ and σ'' are equal to σ or not. The black dotted curves in Fig. 3b, c show the predicted results of the TA amplitudes by assuming identical cross-sections, i.e., σ = σ ′ = σ'' = .’ The correct version states ‘σ′ and σ′′ are equal” instead of ‘σ′ and σ'' are equal’ and ‘σ = σ′ = σ′′’ in place of ‘σ = σ ′ = σ'' = ’.

This has been corrected in both the PDF and HTML versions of the Article.
In situ disentangling surface state transport channels of a topological insulator thin film by gating
Authors: Lüpke Felix , Just Sven , Eschbach Markus , Heider Tristan , Młyńczak Ewa , Lanius Martin , Schüffelgen Peter , Rosenbach Daniel , von den Driesch Nils , Cherepanov Vasily , Mussler Gregor , Plucinski Lukasz , Grützmacher Detlev , Schneider Claus M. , Tautz F. Stefan , Voigtländer Bert
Published: September 2018

In the thin film limit, the surface state of a three-dimensional topological insulator gives rise to two parallel conduction channels at the top and bottom surface of the film, which are difficult to disentangle in transport experiments. Here, we present gate-dependent multi-tip scanning tunneling microscope transport measurements combined with photoemission experiments all performed in situ on pristine BiSbTe3 thin films. To analyze the data, we develop a generic transport model including quantum capacitance effects. This approach allows us to quantify the gate-dependent conductivities, charge carrier concentrations, and mobilities for all relevant transport channels of three-dimensional topological insulator thin films (i.e., the two topological surface state channels, as well as the interior of the film). For the present sample, we find that the conductivity in the bottom surface state channel is minimized below a gate voltage of Vgate = −34 V and the top surface state channel dominates the transport through the film.
Dominance of cropland reduces the pollen deposition from bumble bees
Authors: Pfister Sonja C. , Eckerter Philipp W. , Krebs Julius , Cresswell James E. , Schirmel Jens , Entling Martin H.
Published: September 2018

Intensive agricultural landscapes can be hostile for bees due to a lack of floral and nesting resources, and due to management-related stress such as pesticide use and soil tillage. This threatens the pollination services that bees deliver to insect-pollinated crops. We studied the effects of farming intensity (organic vs. conventional, number of insecticide applications) and availability of semi-natural habitats at the field and landscape scale on pollinator visits and pollen delivery to pumpkin in Germany. We found that wild bumble bees were the key pollinators of pumpkin in terms of pollen delivery, despite fivefold higher visitation frequency of honey bees. Critically, we observed that the area of cropland had stronger effects on bees’ pollen deposition than the area of seminatural habitats. Specifically, a 10% increase of the proportion of cropland reduced pollen delivery by 7%. Pumpkin provides a striking example for a key role of wild pollinators in crop pollination even at high numerical dominance of honey bees. In addition, our findings suggest that habitat conversion to agricultural land is a driver of deteriorating pollination. This underlines the importance to maintain sufficient areas of non-crop habitats in agricultural landscapes.
How morphological development can guide evolution
Authors: Kriegman Sam , Cheney Nick , Bongard Josh
Published: September 2018

Organisms result from adaptive processes interacting across different time scales. One such interaction is that between development and evolution. Models have shown that development sweeps over several traits in a single agent, sometimes exposing promising static traits. Subsequent evolution can then canalize these rare traits. Thus, development can, under the right conditions, increase evolvability. Here, we report on a previously unknown phenomenon when embodied agents are allowed to develop and evolve: Evolution discovers body plans robust to control changes, these body plans become genetically assimilated, yet controllers for these agents are not assimilated. This allows evolution to continue climbing fitness gradients by tinkering with the developmental programs for controllers within these permissive body plans. This exposes a previously unknown detail about the Baldwin effect: instead of all useful traits becoming genetically assimilated, only traits that render the agent robust to changes in other traits become assimilated. We refer to this asdifferential canalization. This finding also has implications for the evolutionary design of artificial and embodied agents such as robots: robots robust to internal changes in their controllers may also be robust to external changes in their environment, such as transferal from simulation to reality or deployment in novel environments.
Optimization of cell-laden bioinks for 3D bioprinting and efficient infection with influenza A virus
Authors: Berg Johanna , Hiller Thomas , Kissner Maya S. , Qazi Taimoor H. , Duda Georg N. , Hocke Andreas C. , Hippenstiel Stefan , Elomaa Laura , Weinhart Marie , Fahrenson Christoph , Kurreck Jens
Published: September 2018

Bioprinting is a new technology, which arranges cells with high spatial resolution, but its potential to create models for viral infection studies has not yet been fully realized. The present study describes the optimization of a bioink composition for extrusion printing. The bioinks were biophysically characterized by rheological and electron micrographic measurements. Hydrogels consisting of alginate, gelatin and Matrigel were used to provide a scaffold for a 3D arrangement of human alveolar A549 cells. A blend containing 20% Matrigel provided the optimal conditions for spatial distribution and viability of the printed cells. Infection of the 3D model with a seasonal influenza A strain resulted in widespread distribution of the virus and a clustered infection pattern that is also observed in the natural lung but not in two-dimensional (2D) cell culture, which demonstrates the advantage of 3D printed constructs over conventional culture conditions. The bioink supported viral replication and proinflammatory interferon release of the infected cells. We consider our strategy to be paradigmatic for the generation of humanized 3D tissue models by bioprinting to study infections and develop new antiviral strategies.
Spatial separation of catches in highly mixed fisheries
Authors: Dolder Paul J. , Thorson James T. , Minto Cóilín
Published: September 2018

Mixed fisheries are the dominant type of fishery worldwide. Overexploitation in mixed fisheries occurs when catches continue for available quota species while low quota species are discarded. As EU fisheries management moves to count all fish caught against quota (the “landing obligation”), the challenge is to catch available quota within new constraints, else lose productivity. A mechanism for decoupling exploitation of species caught together is spatial targeting, which remains challenging due to complex fishery and population dynamics. How far spatial targeting can go to practically separate species is often unknown and anecdotal. We develop a dimension-reduction framework based on joint dynamic species distribution modelling to understand how spatial community and fishery dynamics interact to determine species and size composition. In application to the highly mixed fisheries of the Celtic Sea, clear common spatial patterns emerge for three distinct assemblages. While distribution varies interannually, the same species are consistently found in higher densities together, with more subtle differences within assemblages, where spatial separation may not be practically possible. We highlight the importance of dimension reduction techniques to focus management discussion on axes of maximal separation and identify spatiotemporal modelling as a scientific necessity to address the challenges of managing mixed fisheries.
Interface morphology effect on the spin mixing conductance of Pt/Fe3O4 bilayers
Authors: Pham Thi Kim Hang , Ribeiro Mário , Park Jun Hong , Lee Nyun Jong , Kang Ki Hoon , Park Eunsang , Nguyen Van Quang , Michel Anny , Yoon Chong Seung , Cho Sunglae , Kim Tae Hee
Published: September 2018

Non-magnetic (NM) metals with strong spin-orbit coupling have been recently explored as a probe of interface magnetism on ferromagnetic insulators (FMI) by means of the spin Hall magnetoresistance (SMR) effect. In NM/FMI heterostructures, increasing the spin mixing conductance (SMC) at the interface comes as an important step towards devices with maximized SMR. Here we report on the study of SMR in Pt/Fe3O4 bilayers at cryogenic temperature, and identify a strong dependence of the determined real part of the complex SMC on the interface roughness. We tune the roughness of the Pt/Fe3O4 interface by controlling the growth conditions of the Fe3O4 films, namely by varying the thickness, growth technique, and post-annealing processes. Field-dependent and angular-dependent magnetoresistance measurements sustain the clear observation of SMR. The determined real part of the complex SMC of the Pt/Fe3O4 bilayers ranges from 4.96 × 1014 Ω−1 m−2 to 7.16 × 1014 Ω−1 m−2 and increases with the roughness of the Fe3O4 underlayer. We demonstrate experimentally that the interface morphology, acting as an effective interlayer potential, leads to an enhancement of the spin mixing conductance.
Author Correction: Matrix metalloproteinase-9 activity and a downregulated Hedgehog pathway impair blood-brain barrier function in an in vitro model of CNS tuberculosis
Authors: Brilha Sara , Ong Catherine W. M. , Weksler Babette , Romero Nacho , Couraud Pierre-Olivier , Friedland Jon S.
Published: September 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
An incoherent feed-forward loop switches the Arabidopsis clock rapidly between two hysteretic states
Authors: Joanito Ignasius , Chu Jhih-Wei , Wu Shu-Hsing , Hsu Chao-Ping
Published: September 2018

In higher plants (e.g., Arabidopsis thaliana), the core structure of the circadian clock is mostly governed by a repression process with very few direct activators. With a series of simplified models, we studied the underlying mechanism and found that the Arabidopsis clock consists of type-2 incoherent feed-forward loops (IFFLs), one of them creating a pulse-like expression in PRR9/7. The double-negative feedback loop between CCA1/LHY and PRR5/TOC1 generates a bistable, hysteretic behavior in the Arabidopsis circadian clock. We found that the IFFL involving PRR9/7 breaks the bistability and moves the system forward with a rapid pulse in the daytime, and the evening complex (EC) breaks it in the evening. With this illustration, we can intuitively explain the behavior of the clock under mutant conditions. Thus, our results provide new insights into the underlying network structures of the Arabidopsis core oscillator.
Multilayer homogeneous dielectric filler for electromagnetic invisibility
Authors: Serna Alberto , Molina Luis J. , Rivero Javier , Landesa Luis , Taboada José M.
Published: September 2018

In recent years, invisibility has become a research area of increasing interest due to the advances in material engineering. It may be possible to achieve invisibility through cloaking devices by coating the body using one or more layers of materials with the proper electromagnetic properties. By using techniques associated to plasmonic cloaking it is maybe possible to obtain also invisibility for small objects with several layers of homogeneous materials working from inside the object. We demonstrate numerically that it is, therefore, possible to achieve invisibility through an inner system based on scattering cancellation techniques.
Development of a novel Hsp90 inhibitor NCT-50 as a potential anticancer agent for the treatment of non-small cell lung cancer
Authors: Hyun Seung Yeob , Le Huong Thuy , Nguyen Cong-Truong , Yong Young-Sik , Boo Hye-Jin , Lee Ho Jin , Lee Ji-Sun , Min Hye-Young , Ann Jihyae , Chen Jie , Park Hyun-Ju , Lee Jeewoo , Lee Ho-Young
Published: September 2018

Despite the development of advanced therapeutic regimens such as molecular targeted therapy and immunotherapy, the 5-year survival of patients with lung cancer is still less than 20%, suggesting the need to develop additional treatment strategies. The molecular chaperone heat shock protein 90 (Hsp90) plays important roles in the maturation of oncogenic proteins and thus has been considered as an anticancer therapeutic target. Here we show the efficacy and biological mechanism of a Hsp90 inhibitor NCT-50, a novobiocin-deguelin analog hybridizing the pharmacophores of these known Hsp90 inhibitors. NCT-50 exhibited significant inhibitory effects on the viability and colony formation of non-small cell lung cancer (NSCLC) cells and those carrying resistance to chemotherapy. In contrast, NCT-50 showed minimal effects on the viability of normal cells. NCT-50 induced apoptosis in NSCLC cells, inhibited the expression and activity of several Hsp90 clients including hypoxia-inducible factor (HIF)-1α, and suppressed pro-angiogenic effects of NSCLC cells. Further biochemical and in silico studies revealed that NCT-50 downregulated Hsp90 function by interacting with the C-terminal ATP-binding pocket of Hsp90, leading to decrease in the interaction with Hsp90 client proteins. These results suggest the potential of NCT-50 as an anticancer Hsp90 inhibitor.