bluuebunny/crossref_metadata_2025 huggingface dataset:
A Structural Model for the Iron–Nitrosyl Adduct of Gentisate Dioxygenase
Authors: Banerjee Atanu , Li Jia , Speelman Amy L. , White Corey J. , Pawlak Piotr L. , Brennessel William W. , Lehnert Nicolai , Chavez Ferman A.
Published: October 2018

We present the synthesis, properties, and characterization of [Fe(T1Et4iPrIP)(NO)(H2O)2](OTf)2 (1) {T1Et4iPrIP = Tris(1‐ethyl‐4‐isopropyl‐imidazolyl)phosphine} as a model for the nitrosyl adduct of gentisate 1,2‐dioxygenase (GDO). The further characterization of [Fe(T1Et4iPrIP)(THF)(NO)(OTf)](OTf) (2) which was previously communicated (Inorg. Chem. 2014, 53, 5414) is also presented. The weighted average Fe–N–O angle of 162° for 1 is very close to linear (≥ 165°) for these types of complexes. The coordinated water ligands participate in hydrogen bonding interactions. The spectral properties (EPR, UV/Vis, FTIR) for 1 are compared with 2 and found to be quite comparable. Complex 1 closely follows the relationship between the Fe–N–O angle and NO vibrational frequency which was previously identified for six‐coordinate {FeNO}7 complexes. Liquid FTIR studies on 2 indicate that the ν(NO) vibration position is sensitive to solvent shifting to lower energy (relative to the solid) in donor solvent THF and shifting to higher energy in dichloromethane. The basis for this behavior is discussed. The Keq for NO binding in 2 was calculated in THF and found to be 470 m–1. Density functional theory (DFT) studies on 1 indicate donation of electron density to the iron center from the π* orbitals of formally NO–. Such a donation accounts for the near linearity of the Fe–N–O bond and the large ν(NO) value of 1791 cm–1.
Optimization design and rock‐breaking characteristics analysis of a self‐propelled swirling multi‐jet bit
Authors: Bi Gang , Li Mengmeng , Dou Liangbin , Qu Zhan , Zhao Kai
Published: October 2018

High rock‐breaking efficiency with limited discharge rate and increasing the extension capacity of the radial horizontal hole as far as possible are the key of the novel radial horizontal drilling technology. The performance of jet bit is the primary problem to be solved in this key technology. Based on multijet bit, a self‐propelled swirling jet bit was developed, and the design method was also presented. By conducting rock‐breaking experiments, the type and structural parameters of the self‐propelled swirling jet bit were optimized. The results demonstrate that when the jet pressure and standoff distance are constant, the rock‐breaking efficiency of self‐propelled combined swirling and round multijet bit is better than that of a self‐propelled swirling multijet bit. The combined swirling and round multijet bit with 1 + 4 holes is optimal. Since many structural parameters influence the rock‐breaking efficiency of the self‐propelled swirling jet bit, the optimal values for the structural parameters can be determined by adjusting the rock‐breaking capacity and drilling performance with different structural parameters. The proposed novel jet bit improves the speed of radial horizontal drilling significantly.
Who benefits most in disease management programs: Improving target efficiency
Authors: Simcoe Timothy , Catillon Maryaline , Gertler Paul
Published: October 2018

Disease management programs aim to reduce cost by improving the quality of care for chronic diseases. Evidence of their effectiveness is mixed. Reducing health care spending sufficiently to cover program costs has proved particularly challenging. This study uses a difference in differences design to examine the impact of a diabetes disease management program for high risk patients on preventive tests, health outcomes, and cost of care. Heterogeneity is examined along the dimensions of severity (measured using the proxy of poor glycemic control) and preventive testing received in the baseline year. Although disease management programs tend to focus on the sickest, the impact of this program concentrates in the group of people who had not received recommended tests in the preintervention period. If confirmed, such findings are practically important to improve cost‐effectiveness in disease management programs by targeting relevant subgroups defined both based on severity and on (missing) test information.
Regulatory T Cells Restrict Permeability to Bacterial Antigen Translocation and Preserve Short‐Chain Fatty Acids in Experimental Cirrhosis
Authors: Juanola Oriol , Piñero Paula , Gómez‐Hurtado Isabel , Caparrós Esther , García‐Villalba Rocío , Marín Alicia , Zapater Pedro , Tarín Fabián , González‐Navajas José M. , Tomás‐Barberán Francisco A. , Francés Rubén
Published: October 2018

Intestinal permeability to translocation of bacterial products is increased in cirrhosis. Regulatory T cells (Tregs) remain central to the interplay between the host and microbial milieu. We propose that Tregs are involved in promoting gut barrier integrity and a balanced interaction with gut microbiota–derived short‐chain fatty acids (SCFAs). Carbon tetrachloride cirrhosis was induced in wild‐type and recombination activating gene 1 (Rag1)‐/‐ mice. Naive T cells and Treg cells were transferred into Rag1
‐/‐ mice. Intestinal permeability was assessed in vivo after lipopolysaccharide (LPS) oral administration, and bacterial DNA presence was evaluated in mesenteric lymph nodes. Transcript and protein levels of tight‐junction (TJ) proteins were measured in colonic tissue. Intestinal T helper profile in response to Escherichia coli (E. coli) was determined by flow cytometry. SCFAs were measured by gas chromatography–mass spectrometry in colonic content before and after E. coli challenge. Rag1
‐/‐ mice showed significantly increased permeability to LPS and bacterial DNA translocation rate compared with control mice. Naive T and Treg cotransfer significantly reduced gut permeability to bacterial antigen translocation and restored TJ protein expression in Rag1
‐/‐ mice. Naive T and Treg replenishment in Rag1
‐/‐ mice restrained proinflammatory differentiation of intestinal lymphocytes in response to E. coli. The main SCFA concentration resulted in significant reduction in Rag1
‐/‐ mice after E. coli administration but remained unaltered after naive T and Tregs cotransfer. The reduced expression of SCFA receptors induced by E. coli was reestablished following naive T and Treg reconstitution in Rag1
‐/‐ mice. Conclusion: The restriction of gut permeability, local inflammatory differentiation, and loss of bacteria‐derived SCFAs foster the value of Tregs in preventing bacterial translocation in cirrhosis.
What does unconventional monetary policy do to stock markets in the euro area?
Authors: Chebbi Tarek
Published: October 2018

This paper investigates the impact of the European Central Bank's unconventional monetary surprises on major European stock markets. Three measures for surprises are used: (a) the change in domestic 10‐year government bond yields, (b) the change in the spread between German and Italian (Spanish) 10‐year bond yields, and (c) the change in yields of a safe euro‐denominated asset, such as German bonds. I show that unconventional monetary policy surprises significantly influence stock returns. For instance, monetary decisions that cause a decrease in Italian (Spanish) sovereign spread led to an increase in the stock returns. In addition, I find that a positively surprising shock—a fall in the domestic bond yield and an increase in German interest rates—leads to higher stock returns. Finally, sovereign spreads seemed to have larger effects on stock returns both during crisis and postcrisis years.
Do demographics affect monetary policy transmission in Canada?
Authors: Kronick Jeremy , Ambler Steve
Published: October 2018

Using a panel of macroeconomic data for Canada and its 10 provinces, we estimate the dynamic effects of monetary policy shocks from the mid‐1980s until the present. We then relate the change in the impact of these shocks to macroeconomic factors including demographics, specifically changes in the old age dependency ratio. We find that the inflation‐targeting regime has had an ambiguous effect on the impact of monetary policy shocks in Canada. On the other hand, changing demographics have unambiguously reduced the impact of monetary policy shocks. This can help to explain tepid inflation since the financial crisis and could eventually undermine the effectiveness of Canada's inflation targeting regime.
Can cooperative game theory solve the low‐risk puzzle?
Authors: Auer Benjamin R. , Hiller Tobias
Published: October 2018

In this article, we illustrate that cooperative game theory may have the potential to solve the low‐risk puzzle, which has become one of the most important in modern finance because its implication of a negative risk‐return trade‐off poses a challenge to traditional models of asset prices. Using several simulation settings, we highlight that quantifying risk by means of assets' Shapley values, that is, assets' contributions to overall portfolio risk, instead of classic measures supplies a (more) positive risk‐return relationship in many practically relevant cases. This is partially attributable to the fact that the game‐theoretic risk measure captures more investment‐relevant information than commonly used alternatives.
The impacts of global economic policy uncertainty on stock market returns in regime switching environment: Evidence from sectoral perspectives
Authors: Hoque Mohammad Enamul , Zaidi Mohd Azlan Shah
Published: October 2018

This study contributes in building emerging literature by investigating the impacts of global economic policy uncertainty on Malaysian sectoral stock performance. This study models sectoral stock returns as time‐varying transition probability Markovian processes and employs two‐stage Markov‐switching model for findings impacts of global economic policy uncertainty on sectoral stock returns in regime switching environment. The empirical results reveal that linear framework unable to detect the effects global economic policy uncertainty, and the Markov‐switching model exhibits significant effects of global economic policy uncertainty on all sectoral stock returns excluding technology sector in Malaysia stock market. The findings also expose that the effects of global economic policy uncertainty vary across regime states, sectors, and nature of effects, where the negative effects of global economic policy uncertainty dominate over positive effects. The global economic policy uncertainty exhibits greater impacts on stock returns in high‐volatility regime. Thus, the findings confirm the existence of asymmetric, nonlinear, nonmonotonic, and state‐dependent relationship between global economic policy uncertainty and sectoral stock returns in Malaysia. Therefore, the overall empirical findings can be applied in asset pricing and investment decision‐making purposes. The findings also suggest that global economic policy uncertainty can be a systemic risk factor and predictor of stock market returns.
Ubiquitin‐independent, Proteasome‐mediated targeted degradation of KRAS in pancreatic adenocarcinoma cells using an engineered ornithine decarboxylase/antizyme system
Authors: Ma Yihui , Xu Jingjing , Huang Pei , Bai Xue , Gao Hanqing
Published: October 2018

The oncogene KRAS not only promotes the tumorigenesis of pancreatic cancers but also is required for the malignant progression and metastasis of these cancers. Many methods have been explored to influence the malignant biological behavior of these cancers by targeting mutant KRAS. The ornithine decarboxylase/antizyme (ODC/AZ) system is another protein degradation pathway that exists in nature. The formation of an ODC and protein substrate complex through direct combination can promote its degradation by the 26S proteasome without ubiquitination, and this process can be catalyzed by AZ. In this study, we designed and reconstructed a chimeric fusion protein (named RC‐ODC). The engineered fusion protein RC‐ODC was confirmed to interact with the mutant KRAS oncoprotein in a co‐immunoprecipitation assay, and the introduction of both RC‐ODC and AZ resulted in degradation of the exogenous and endogenous mutant KRAS oncoprotein at the post‐translational level independent of ubiquitination in vitro. Along with a decreased KRAS level, suppression of PANC‐1 cell proliferation was detected in vitro and in vivo, and meanwhile downregulation of phosphorylated extracellular signal‐regulated kinase 1/2 (ERK1/2) was also observed. Targeted degradation of the KRAS oncoprotein through the ODC/AZ pathway at the post‐translational level may reflect a more effective future therapeutic strategy for pancreatic cancer patients. © 2018 The Authors. IUBMB Life published by Wiley Periodicals,Inc. on behalf of International Union of Biochemistry and Molecular Biology, 71(1):57–65, 2019
PiT1/Slc20a1 Is Required for Endoplasmic Reticulum Homeostasis, Chondrocyte Survival, and Skeletal Development
Authors: Couasnay Greig , Bon Nina , Devignes Claire-Sophie , Sourice Sophie , Bianchi Arnaud , Véziers Joëlle , Weiss Pierre , Elefteriou Florent , Provot Sylvain , Guicheux Jérôme , Beck-Cormier Sarah , Beck Laurent
Published: October 2018

During skeletal mineralization, the sodium-phosphate co-transporter PiT1Slc20a1 is assumed to meet the phosphate requirements of bone-forming cells, although evidence is missing. Here, we used a conditional gene deletion approach to determine the role of PiT1 in growth plate chondrocytes. We show that PiT1 ablation shortly after birth generates a rapid and massive cell death in the center of the growth plate, together with an uncompensated endoplasmic reticulum (ER) stress, characterized by morphological changes and increased Chop, Atf4, and Bip expression. PiT1 expression in chondrocytes was not found at the cell membrane but co-localized with the ER marker ERp46, and was upregulated by the unfolded protein response cascade. In addition, we identified the protein disulfide isomerase (Pdi) ER chaperone as a PiT1 binding partner and showed that PiT1 ablation impaired Pdi reductase activity. The ER stress induced by PiT1 deficiency in chondrocytes was associated with intracellular retention of aggrecan and vascular endothelial growth factor A (Vegf-A), which was rescued by overexpressing a phosphate transport-deficient mutant of PiT1. Our data thus reveal a novel, Pi-transport independent function of PiT1, as a critical modulator of ER homeostasis and chondrocyte survival during endochondral ossification. © 2018 American Society for Bone and Mineral Research.
Chondrocytes Promote Vascularization in Fracture Healing Through a FOXO1-Dependent Mechanism
Authors: Zhang Citong , Feinberg Daniel , Alharbi Mohammed , Ding Zhenjiang , Lu Chanyi , O'Connor J Patrick , Graves Dana T
Published: October 2018

Chondrocytes play an essential role in fracture healing by producing cartilage, which forms an anlage for endochondral ossification that stabilizes the healing fracture callus. More recently it has been appreciated that chondrocytes have the capacity to produce factors that may affect the healing process. We examined the role of chondrocytes in angiogenesis during fracture healing and the role of the transcription factor forkhead box-O 1 (FOXO1), which upregulates wound healing in soft tissue. Closed fractures were induced in experimental mice with lineage-specific FOXO1 deletion by Cre recombinase under the control of a collagen-2α1 promoter element (Col2α1Cre+FOXO1L/L) and Cre recombinase negative control littermates containing flanking loxP sites (Col2α1Cre–FOXO1L/L). Experimental mice had significantly reduced CD31+ new vessel formation. Deletion of FOXO1 in chondrocytes in vivo suppressed the expression of vascular endothelial growth factor-A (VEGFA) at both the protein and mRNA levels. Overexpression of FOXO1 in chondrocytes in vitro increased VEGFA mRNA levels and VEGFA transcriptional activity whereas silencing FOXO1 reduced it. Moreover, FOXO1 interacted directly with the VEGFA promoter and a deacetylated FOXO1 mutant enhanced VEGFA expression whereas an acetylated FOXO1 mutant did not. Lastly, FOXO1 knockdown by siRNA significantly reduced the capacity of chondrocytes to stimulate microvascular endothelial cell tube formation in vitro. The results indicate that chondrocytes play a key role in angiogenesis which is FOXO1 dependent and that FOXO1 in chondrocytes regulates a potent angiogenic factor, VEGFA. These studies provide new insight into fracture healing given the important role of vessel formation in the fracture repair process. © 2018 American Society for Bone and Mineral Research.
Long noncoding RNA NEAT1 promotes cell proliferation, migration, and invasion in hepatocellular carcinoma through interacting with miR‐384
Authors: Zhu Liying , Yang Nenghong , Li Chengcheng , Liu Guoqi , Pan Wei , Li Xing
Published: October 2018

It was reported that long non‐coding RNA nuclear‐enriched abundant transcript 1 (NEAT1) is involved in hepatocellular carcinoma (HCC). However, the underlying mechanism of tumorigenesis is still largely unclear. Here, we found that NEAT1 is remarkably upregulated in HCC tissues and cell lines. Overexpression of NEAT1 notably accelerated HCC cell proliferation, migration, and invasion. Knockdown of NEAT1 significantly inhibited HCC cell proliferation, migration and invasion. MiR‐384 expression was lower in HCC tissues and cell lines than adjacent nontumor tissues and L02 cell. MiR‐384 exhibited the functions of tumor‐suppressive. The expression of miR‐384 was negatively correlated with the expression of NEAT1. Overexpression of NEAT1 reduced miR‐384 expression, whereas inhibition of miR‐384 led to a distinct upregulation of NEAT1 expression. In addition, we provided evidence that miR‐384 was directly bound to the sequence of NEAT1 by luciferase reporter and RNA‐binding protein immunoprecipitation assays. Overexpression of miR‐384 inhibited NEAT1 function. Thus, we demonstrated that NEAT1 promotes the malignant biological properties of hepatocellular carcinoma by negatively regulating miR‐384.
Synthesis, Molecular Docking, and Biological Evaluation of Some Novel Bis‐heterocyclic Compounds Based N,N′‐([1,1′‐biphenyl]‐4,4′‐diyl)bis(2‐cyanoacetamide) as Potential Anticancer Agents
Authors: Metwally Nadia Hanafy , Abdelrazek Fathy Mohamed , Eldaly Salwa Magdy
Published: October 2018

Synthesis of unreported hitherto N,N′‐([1,1′‐biphenyl]‐4,4′‐diyl)bis(2‐cyanoacetamide) as a precursor to synthesize bis‐chromenes, bis‐thiazole derivatives, and bis‐pyridizines. The structures of the newly synthesized compounds were established by their elemental analyses and spectral data. Some of the newly synthesized compounds were tested for in vitro activity against hepatocellular carcinoma, human breast cancer, and human cervical carcinoma cell lines compared with the employed standard antitumor drug (doxorubicin), and the results revealed that the starting N,N′‐([1,1′‐biphenyl]‐4,4′‐diyl)bis(2‐cyanoacetamide) is more potent activity than doxorubicin against hepatocellular carcinoma and human cervical carcinoma.
Top‐down analysis of novel synthetic branched proteins
Authors: Gomes Fabio , Lemma Betsegaw , Abeykoon Dulith , Chen Dapeng , Wang Yan , Fushman David , Fenselau Catherine
Published: October 2018

A strategy for top‐down analysis of branched proteins has been reported earlier, which relies on electron transfer dissociation assisted by collisional activation, and software designed for graphic interpretation of tandem mass spectra and adapted for branched proteins. In the present study, the strategy is applied to identify unknown and novel products of reactions in which rationally mutated proteoforms of Rub1 are used to probe the selectivity of E1 and E2 enzymes normally active in ubiquitination. To test and demonstrate this application, components and attachment sites of three branched dimers are deduced and the mutations are confirmed.
Human leukocyte antigen polymorphisms and Kaposi's sarcoma‐associated herpesvirus infection outcomes: A call for deeper exploration
Authors: Fang Qiwen , Liu Zhenqiu , Zhang Tiejun
Published: October 2018

Host genetic background may influence the immunity to resist viral infection. As the most polymorphic loci in the entire human genome, the human leukocyte antigen (HLA) system plays an important role in innate and adaptive immune responses to many invading pathogens. Studies have shown that an association might exist between HLA polymorphisms and susceptibility to Kaposi's sarcoma‐associated herpesvirus (KSHV) infection and associated diseases. However, discrepant conclusions were reached among different subjects with different detection methods. Therefore, it is now urgent to summarize current results and figure out the achievements and deficiencies of the existing research for the reference to future studies. A better understanding about the role of HLA polymorphisms in KSHV infection outcome would enable us to elucidate the pathways through which the virus evades the host defense system and improve strategies for the prevention and treatment of KSHV infection.
Insights into major facilitator superfamily domain‐containing protein‐2a (Mfsd2a) in physiology and pathophysiology. What do we know so far?
Authors: Eser Ocak Pinar , Ocak Umut , Sherchan Prativa , Zhang John H. , Tang Jiping
Published: October 2018

Major facilitator superfamily domain‐containing protein‐2a (Mfsd2a) which was considered as an orphan transporter has recently gained attention for its regulatory role in the maintenance of proper functioning of the blood–brain barrier. Besides the major role of Mfsd2a in maintaining the barrier function, increasing evidence has emerged with regard to the contributions of Mfsd2a to various biological processes such as transport, cell fusion, cell cycle, inflammation and regeneration, managing tumor growth, functioning of other organs with barrier functions or responses to injury. The purpose of this article is to review the different roles of Mfsd2a and its involvement in the physiological and pathophysiological processes primarily in the central nervous system and throughout the mammalian body under the lights of the current literature.
On the global well‐posedness for the two‐dimensional Boussinesq equations with horizontal dissipation
Authors: Guo Meiqi , Zhang Qian
Published: October 2018

In this paper, we study the global well‐posedness for the two‐dimensional nonlinear Boussinesq equations with horizontal dissipation. The method we adopted is the smoothing effect in horizontal direction and the low‐high decomposition technique.
Nonexistence of coexisting steady‐state solutions of Dirichlet problem for a cross‐diffusion model
Authors: Zhu Ningning , Tang De
Published: October 2018

We study a special case of Shigesada–Kawasaki–Teramoto (SKT) model for two competing species with the Dirichlet boundary conditions. In our case, one of the species is not influenced by self‐diffusion or cross‐diffusion. We specify the explicit range of parameters by contradiction such that there are no coexisting steady‐state solutions to the model.
Milk Powder Co‐Supplemented with Inulin and Resistant Dextrin Improves Glycemic Control and Insulin Resistance in Elderly Type 2 Diabetes Mellitus: A 12‐Week Randomized, Double‐Blind, Placebo‐Controlled Trial
Authors: Cai Xiaxia , Yu Huanling , Liu Lan , Lu Tong , Li Jingjie , Ji Yacheng , Le Zhiyin , Bao Lei , Ma Weiwei , Xiao Rong , Yang Yuexin
Published: October 2018

Scope

The objective of the present study is to evaluate the effects of milk powder co‐supplemented with inulin and resistant dextrin (MPCIR) on elderly patients with type 2 diabetes mellitus (T2DM).

Methods and results

A randomized, double‐blind, placebo‐controlled clinical trial is carried out among elderly T2DM patients. The subjects recruited from the community are randomly assigned to either the MPCIR group or placebo group for 12 weeks intervention. Each group receives 45 g milk powder with or without inulin and resistant dextrin. Anthropometric and metabolic variables are measured. For the MPCIR group, systolic blood pressure (BP) and diastolic BP are reduced significantly by 5.45 and 4.56 mm Hg (p < 0.001, vs placebo group), respectively. Compared with the placebo group, the fasting and 2‐h postprandial plasma glucose levels, glycosylated serum protein, and insulin resistance index of the MPCIR group are significantly decreased by 0.96 mmol L–1, 1.47 mmol L–1, 16.33 μmol L–1, and 0.65 respectively (p < 0.001). The MPCIR group shows an increase by 7.09 μIU mL–1 and 20.43 in 2‐h postprandial insulin (p = 0.016) and β‐cell function index (p < 0.001), respectively.

Conclusion

MPCIR supplementation helps to improve glycemic control, insulin resistance, and blood pressure.
Safety of active catheters in MRI: Termination impedance versus RF‐induced heating
Authors: Özen Ali Caglar , Lottner Thomas , Bock Michael
Published: October 2018

Purpose

To investigate the effect of the termination impedance on the RF‐induced heating of active catheters using analytical modeling.

Theory and Methods

Interaction of an arbitrary electric (E) field and an isolated transmission line (TL) embedded in cascaded lossy media was analytically modeled. Termination impedances at the tip and the input sides were expressed as distinct parameters in the current and voltage distribution formulae that are obtained by solving the inhomogeneous wave equations using the Green's function approach. The tip specific absorption rate (SAR) was calculated for different E field configurations. The tip SAR was displayed on a color‐coded Smith chart in terms of the normalized input reflection coefficient. Results of the analytical calculations were compared to transfer function (TF) measurements. An input impedance control unit that is integrated to the interface circuit was introduced.

Results

TFs from analytical model and measurements exhibited similar behaviors. Color‐coded Smith charts shows that the analytical model and measured TF‐based tip SAR depends strongly on the input reflection coefficient. Both for measured and analytical TFs, SAR can deviate up to 70% from the mean value for different input impedance values.

Conclusion

This study shows that it is possible to change the RF‐induced heating characteristics of an active catheter by adjusting the input impedance, and the presented analytical model is in good agreement with TF measurements.
Assessment of flip angle–TR equivalence for standardized dissolved‐phase imaging of the lung with hyperpolarized 129Xe MRI
Authors: Ruppert Kai , Amzajerdian Faraz , Hamedani Hooman , Xin Yi , Loza Luis , Achekzai Tahmina , Duncan Ian F. , Profka Harrilla , Siddiqui Sarmad , Pourfathi Mehrdad , Sertic Federico , Cereda Maurizio F. , Kadlecek Stephen , Rizi Rahim R.
Published: October 2018

Purpose

To investigate the feasibility of describing the impact of any flip angle–TR combination on the resulting distribution of the hyperpolarized xenon‐129 (HXe) dissolved‐phase magnetization in the chest using a single virtual parameter, TR90°,equiv.

Methods

HXe MRI scans with simultaneous gas‐ (GP) and dissolved‐phase (DP) excitation were performed using 2D projection scans in mechanically ventilated rabbits. Measurements with DP flip angles ranging from 6–90° and TRs ranging from 8.3–500 ms were conducted. DP maps based on acquisitions of similar radio frequency pulse‐induced relaxation rates were compared.

Results

The observed distribution of the DP magnetization was strongly affected by acquisition flip angle and TR. However, for flip angles up to 60°, measurements with the same radio frequency pulse‐induced relaxation rates, resulted in very similar DP images despite the presence of significant macroscopic gas transport processes. For flip angles approaching 90°, the downstream signal component decreased noticeably relative to acquisitions with lower flip angles. Nevertheless, the total DP signal continued to follow an empirically verified conversion equation over the entire investigated parameter range, which yields the equivalent TR of a hypothetical 90° measurement for any experimental flip angle–TR combination.

Conclusion

We have introduced a method for converting the flip angle and TR of a given HXe DP measurement to a standardized metric based on the virtual quantity, TR90°,equiv, using their equivalent RF relaxation rates. This conversion permits the comparison of measurements obtained with different pulse sequence types or by different research groups using various acquisition parameters.
Weak correlation of bleeding scores to platelet electron microscopy: A retrospective chart review of pediatric patients with delta‐storage pool disorder
Authors: Nessle C. N. , Ghosal S. , Mathews C. , Taylor D. , Myers J. , Raj A. , Panigrahi A.
Published: October 2018

Background

Delta granule storage pool deficiency (δ‐SPD) is a rare platelet disorder in which a deficiency of platelet granules leads to poor aggregation, resulting in varying clinical bleeding phenotypes. Children with δ‐SPD have variable laboratory results, making the proper diagnosis and evaluation controversial.

Objectives

To describe the demographic and laboratory trends of this population and to assess the value of electron microscopy in diagnostic evaluation and its correlation to bleeding symptoms.

Methods

We performed a retrospective review of 109 pediatric patients diagnosed with δ‐SPD. We collected demographic information and bleeding scores using a validated bleeding assessment tool. A descriptive and exploratory analysis was performed.

Results

The majority of patients were female, with an average age at diagnosis of 11.61 years. Females were diagnosed at a significantly older age presenting most often with menorrhagia, while males presented most commonly with epistaxis. The majority showed normal lumiaggregometry, the mean platelet electron microscopy (PEM) value was 2.37, and the mean bleeding score was 6. Bleeding assessment tool and PEM had a significantly weak correlation.

Conclusions

Patients with more dense granules per platelet had higher bleeding scores than those with fewer dense granules per platelet. The current body of evidence does not favor the use of PEM in routine clinical practice, and results are difficult to interpret. In patients with severe mucocutaneous bleeding symptoms and normal platelet aggregation studies, consideration should be given to an alternative diagnosis and further evaluation is warranted.
Experimental investigation of the single screw extruder with grooved melting zone
Authors: Chen Ke , Lin Xudong , Xue Ping , Jia Mingyin , Li Chenxin
Published: October 2018

The barrel grooves of feeding zone were extended to the melting zone in a single screw extruder (SSE). A novel melting mechanism for SSE with grooved melting zone and anticompression screw was proposed, and a new hydraulic quick‐opening SSE platform was specifically designed and built to verify the model using materials of PP and HDPE. Comparative experiments were carried out for investigating melting behavior with various combinations of barrels and screws. For the ability of building reasonable pressure, the anticompression screw fits SSE with grooved melting zone. The solids in barrel grooves were melted quickly at the beginning of melting zone and kept melted state in the entire melting zone, which greatly improved the melting of solids in screw channel. Compared with conventional SSE, it was found that actual melting temperature was about 10°C higher in the case of SSE with grooved melting zone and anticompression screw. Although melting of polymer in the screw channel started at a later time, the melting length of SSE with grooved melting zone was greatly shortened by 50%, compared with that of traditional extruder. The melting efficiency and the throughout were also improved significantly. POLYM. ENG. SCI., 58:1555–1563, 2018. © 2017 Society of Plastics Engineers
Lung function in a cohort of 5‐year‐old children born very preterm
Authors: Lombardi Enrico , Fainardi Valentina , Calogero Claudia , Puglia Monia , Voller Fabio , Cuttini Marina , Rusconi Franca
Published: October 2018

Objective

We assessed lung function and respiratory health in an area‐based prospective cohort of preschool children born very preterm.

Design

Lung function was measured by interrupter respiratory resistance (Rint) and forced oscillation technique (FOT) (respiratory resistance (Rrs8), reactance (Xrs8), and area under the reactance curve (AX)) at a median age of 5.2 years in a cohort of 194 children born at 22‐31 weeks of gestational age (GA) in Tuscany, Italy. Respiratory symptoms and hospitalizations were also assessed.

Results

Mean (SD) lung function Z‐scores were impaired in preterm children for Rint (0.72 (1.13)), Xrs8 (‐0.28 (1.34)), and AX (0.29 (1.41)). However, only a relatively small proportion of children (14.5‐17.4%) had values beyond the 95th centile or below the 5th. Children with bronchopulmonary dysplasia (BPD) (n = 24) had slightly but not significantly impaired lung function indices in comparison with those without BPD (n = 170). In a multivariable analysis, lower GA was associated with worse lung function indices. Fifty‐five percent of children had a history of wheezing ever and 21% had been hospitalized in their lifetime because of lower respiratory infections; 31% had wheezing in the last 12 months and this was associated with increased Rrs8 (P = 0.04) and AX (P = 0.08), and with decreased Xrs8 (P = 0.04) Z‐scores.

Conclusions

Irrespectively of BPD preschool children born very preterm had impaired lung function indices, as measured by Rint and FOT, and a slightly higher burden of respiratory problems than the general population. GA seems to be crucial for lung development.
Synthesis and Evaluation of 3‐Picrylamino‐1,2,4‐Triazole (PATO) Formulations
Authors: Leonard Philip , Bowden Patrick , Shorty Marvin , Schmitt Matt
Published: October 2018

3‐Picrylamino‐1,2,4‐triazole (PATO) is a thermally stable explosive invented at Los Alamos National Laboratory (LANL) almost half a century ago. Despite a rapid and high yielding synthesis, performance data for this promising explosive are scant. We prepared material using Coburn's synthesis, and discovered that the particle size distribution and morphology leads to difficulty in pressing formulations to high density. Three formulations were made using glycidyl azide polymer (GAP), FK‐800, and Estane 5703/nitroplasticizer (NP) as binders. The maximum pressed density of these formulations was 89 % of theoretical maximum density (TMD). We determined detonation velocity and, for the FK‐800 formulation, detonation pressure. The performance of PATO is similar to TATB at equivalent pressed density.
Synthesis and Characterization of the Guanidine Salt Based on 1,1,2,2‐Tetranitraminoethane (TNAE)
Authors: Zhu Chao , Song Panqi , Qiu Lili , Liu Yang , Xu Zhibin , Meng Zihui
Published: October 2018

A novel method has been successfully developed to synthesize the guanidine salt of 1,1,2,2‐tetranitraminoethane (TNAE). By the use of IR, 1H and 13C NMR spectroscopy, the structure of the guanidine salt of TNAE was thoroughly characterized. In addition to the thermal stability investigated by TG‐DSC, the kinetic parameters of this kind of material including activation energy and the pro‐exponential factor were also calculated by Kissinger equation. The measurements of impact and friction sensitivity were carried out respectively. According to the theoretical performance calculations, the guanidine salt of TNAE exhibited the excellent detonation pressures and velocities. The solubility analysis for guanidine salt of TNAE by HPLC was performed at different temperatures, revealing the solubility increased with the increasing of temperature. And its solubility was proved to be the best in water among all the experimented solvents, ethyl acetate, dichloromethane and acetone followed up. With the great potential in practical application, the guanidine salt of TNAE is of significant value being employed as environmentally friendly gas generant, insensitive explosive and solid propellant.
A role for paracrine interleukin‐6 signaling in the tumor microenvironment in prostate tumor growth
Authors: Yu Shu‐Han , Maynard Janielle P. , Vaghasia Ajay M. , De Marzo Angelo M. , Drake Charles G. , Sfanos Karen S.
Published: October 2018

Background

Interleukin‐6 (IL‐6) is a mediator of inflammation that can facilitate prostate cancer progression. We previously demonstrated that IL‐6 is present in the prostate tumor microenvironment and is restricted almost exclusively to the stromal compartment. The present study examined the influence of paracrine IL‐6 signaling on prostate tumor growth using allograft models of mouse prostate cancer (TRAMP‐C2), colon cancer (MC38), and melanoma (B16) cell lines in wildtype (WT) and IL‐6 knockout (IL‐6−/−) mice.

Methods

Cells were implanted into WT or IL‐6−/− mice and tumor sizes were measured at a 3 to 4 day interval. Serum, tumors, and other organs were collected for IL‐6 analysis by ELISA and RNA in situ hybridization (RISH).

Results

There was a significant reduction in TRAMP‐C2 and B16 tumor size grown in IL‐6−/− mice versus WT mice (P = 0.0006 and P = 0.02, respectively). This trend was not observed for the MC38 cell line. RISH analysis of TRAMP‐C2 tumors grown in WT mice showed that cells present in the tumor microenvironment were the primary source of IL‐6 mRNA, not the TRAMP‐C2 cells. Serum IL‐6 ELISA analyses showed an increase in the circulating levels of IL‐6 in WT mice bearing TRAMP‐C2 tumors. Similar phospho‐STAT3 expression and tumor vascularization were observed in TRAMP‐C2 tumors grown in WT and IL‐6−/− mice.

Conclusions

Our results are consistent with previous studies in prostate cancer patients demonstrating that paracrine IL‐6 production in the tumor microenvironment may influence tumor growth. Additionally, these data provide evidence that elevated systemic IL‐6 levels may be involved in tumor growth regulation in prostate cancer, and are not simply caused by or indicative of tumor burden.
Lack of combination effects of soy isoflavones and taxane chemotherapy of castration‐resistant prostate cancer
Authors: Eskra Jillian N. , Schlicht Michael J. , Bosland Maarten C.
Published: October 2018

Background

Patients with cancer, including prostate cancer, often use dietary supplements, such as soy or isoflavones, before, during, or after therapy. There is little information about possible interactions between supplements and cancer chemotherapy. There are some reports suggesting enhancement by genistein of taxane chemotherapy for castrate‐resistant prostate cancer (CRPC).

Methods

We investigated whether physiologically attainable concentrations of soy isoflavones (≤10 μM) interact with taxanes on growth inhibition of CRPC cells in vitro and in vivo in nude mice exposed via the diet, on microtubule disassembly in vitro, and on P‐glycoprotein‐mediated drug efflux in 22Rv1 cells and CYP3A4 activity in microsomes.

Results

Genistein, daidzein, and equol did not affect growth of VCaP, 22Rv1, C4‐2, and PC‐3 CRPC cells or growth inhibition of these cells by docetaxel and cabazitaxel. These isoflavones did not inhibit microtubule disassembly in vitro or inhibit the microtubule effects of taxanes and genistein did not bind substantially to microtubules. Genistein considerably inhibited P‐glycoprotein‐mediated drug efflux in 22Rv1 cells and CYP3A4 activity in microsomes. However, dietary supplementation with genistein at 250 and 500 ppm did not affect the tumor growth inhibiting effect of docetaxel on 22Rv1 cells xenografted in nude mice.

Conclusions

Our results with relevant cell models and clinically achievable concentrations of soy isoflavones do not support the notion that genistein or other soy isoflavones can enhance the effects of taxane chemotherapy in CRPC cell and xenograft models. Yet, the inhibitory effects of genistein on drug efflux in 22Rv1 cells and on microsomal CYP3A4 activity raise the possibility that genistein can affect taxane effects on CRPC cells in other circumstances than those we studied, which merits further research.
Do not believe the hype: Using case studies and experimental evidence to show why the HSE is wrong about excluding deflagration‐to‐detonation transitions
Authors: Davis Scott , Pagliaro John , Botwinick Drew , DeBold Thomas , van Wingerden Kees , Allason Dan , Johnson D. Michael
Published: October 2018

A recent report by the UK's Health and Safety Executive postulated that severe explosions can propagate at subsonic speeds but generate overpressures of several bar in open areas and this “new” type of explosion is episodic in nature. The UK Health and Safety Executive (HSE) paper based their findings on a specific interpretation of historical data and “empirical evidence” from previous incidents and selected experimental data. They indicate that their results should guide plant design and risk assessment. The report fails to take account of key evidence from recent large‐scale experimental studies and incident investigations in proposing a hypothetical explosion mechanism over those that are known to occur and are well understood. This has the potential to misdirect efforts to manage such events.

The first part of the article will review a number of incidents and demonstrate that each of these incidents can indeed be explained by fast deflagrations or transition to detonations, in complete contradiction to the HSE findings. The results found at the incident sites will be directly compared against results from recent DDT work and damage. The second part of the paper will present a novel technique for determining the DDT transition velocity from high‐speed video footage of experiments performed at large scales. © 2018 American Institute of Chemical Engineers Process Saf Prog 38: e11998, 2019
Structural, Topography, and Optical Properties of Ba‐Doped Mn3O4 Thin Films for Ammonia Gas Sensing Application
Authors: Najim Aus A. , Darwoysh Hassan H. , Dawood Yasmeen Z. , Hazaa Salah Q. , Salih Ammar T.
Published: October 2018

The fabrication of reliable and cost‐effective gas sensor for low concentrations of toxic gases such as ammonia is still a challenging task, in this work the authors report structural, topography, and optical properties of pure and Ba‐doped Mn3O4 thin films prepared by chemical spray pyrolysis (CSP) as well as its gas sensing performance toward low concentrations of ammonia gas. XRD analyses prove the films have tetragonal spinel structure with a preferred orientation along the direction (103). AFM and SEM measurements show the films have homogeneous with rough surfaces and porous structures. EDS measurement confirms the presence of Mn, O, and Ba elements according to a doping concentration ratio. Optical measurements show the optical band gap redshifts and the bond length expands as Ba concentration increases. The optimal results are achieved in Mn3O4:Ba1% thin films where porous structure, rough surface, high crystallinity, and maximum response toward (20, 30, 40, and 50 ppm) of ammonia gas with great stability. Empirical equations are suggested to evaluate the sensitivity in terms of relative bond length and RMS roughness. These results show the films are good candidates in p‐type MOS gas sensors.
Stimulated Surface Relief Erasing in Amorphous As‐Se Layers: Thermal‐ and Light Induced Effects
Authors: Molnar Sandor , Bohdan Roland , Takats Viktor , Kaganovskii Yuri , Kokenyesi Sandor
Published: October 2018

Here the kinetics of erasing surface relief gratings (SRGs) in amorphous As20Se80 thin films are studied under various temperatures (in the range 298–408 K) and continuous‐wave illumination by band gap light of various intensities (0–2.5 W cm−2) and polarizations. The SRGs with 3.5 and 15 μm periods and 300 nm amplitudes are recorded by two beam interference. By the measurements of erasing kinetics on the grating of two the different periods, the authors are able to separate contributions of viscous flow and photo‐induced (PI) diffusion flow, which the authors consider as independent mechanisms of mass transfer. The authors detect that band gap light illumination does not change the viscosity of chalcogenide films. In contrast to previous results, the authors suggest that mass transport is accelerated by light due to contribution of PI diffusion flow, not by decrease of “pure” viscous flow. Contribution of PI diffusion flow, as well as anisotropy of mass transport under illumination by polarized light, drops with increasing temperature, whereas contribution of viscous flow grows with temperature. By separation of contributions of PI diffusion and viscous flow in mass transfer, the authors can determine PI diffusion coefficients and their temperature dependences.
Effect of ingredients from Chinese herbs on enterovirus D68 production
Authors: Meng Xiangling , Yu Xiaoyan , Liu Chunyu , Wang Ying , Song Fengmei , Huan Chen , Huo Wenbo , Zhang Shuxia , Li Zhaolong , Zhang Jun , Zhang Wenyan , Yu Jinghua
Published: October 2018

Human enterovirus 68 (EVD68) is a primary causative agent for respiratory illness worldwide. Until now, there has been no available medication for treating EVD68‐related diseases. Rheum emodin, artemisinin, astragaloside, pseudolaric acid B, oridonin, and erianin are natural extracts from Chinese herbs that have traditionally been used for the treatment and prevention of epidemic diseases. Our results showed that pseudolaric acid B protected cells from EVD68‐induced cytopathic effects and decreased viral production. However, the same effects were not observed with rheum emodin, astragaloside, or artemisinin. Pseudolaric acid B inhibited EVD68 production by manipulating the host cell cycle in G2/M phase. Further, either oridonin or erianin related G2/M arrest also inhibited viral production. Due to inducing G2/M phase arrest, pseudolaric acid B, oridonin, and erianin might be good candidates for inhibiting EVD68 production, and Chinese herbs with natural compounds inducing G2/M arrest should be considered for the treatment of EVD68‐related diseases.
Minimum sample size for developing a multivariable prediction model: Part I – Continuous outcomes
Authors: Riley Richard D. , Snell Kym I.E. , Ensor Joie , Burke Danielle L. , Harrell Frank E. , Moons Karel G.M. , Collins Gary S.
Published: October 2018

In the medical literature, hundreds of prediction models are being developed to predict health outcomes in individuals. For continuous outcomes, typically a linear regression model is developed to predict an individual's outcome value conditional on values of multiple predictors (covariates). To improve model development and reduce the potential for overfitting, a suitable sample size is required in terms of the number of subjects (n) relative to the number of predictor parameters (p) for potential inclusion. We propose that the minimum value ofnshould meet the following four key criteria: (i) small optimism in predictor effect estimates as defined by a global shrinkage factor of≥0.9; (ii) small absolute difference of≤0.05 in the apparent and adjustedR2; (iii) precise estimation (a margin of error≤10% of the true value) of the model's residual standard deviation; and similarly, (iv) precise estimation of the mean predicted outcome value (model intercept). The criteria require prespecification of the user's chosenpand the model's anticipatedR2as informed by previous studies. The value ofnthat meets all four criteria provides the minimum sample size required for model development. In an applied example, a new model to predict lung function in African‐American women using 25 predictor parameters requires at least 918 subjects to meet all criteria, corresponding to at least 36.7 subjects per predictor parameter. Even larger sample sizes may be needed to additionally ensure precise estimates of key predictor effects, especially when important categorical predictors have low prevalence in certain categories.