bluuebunny/crossref_metadata_2025 huggingface dataset:
An Ectosteric Inhibitor of Cathepsin K Inhibits Bone Resorption in Ovariectomized Mice
Authors: Panwar Preety , Xue Liming , Søe Kent , Srivastava Kamini , Law Simon , Delaisse Jean-Marie , Brömme Dieter
Published: July 2017

The potent cathepsin K (CatK) inhibitor, Tanshinone IIA sulfonic sodium (T06), was tested for its in vitro and in vivo antiresorptive activities. T06 binds in an ectosteric site of CatK remote from its active site and selectively inhibits collagen degradation with an IC50 value of 2.7 ± 0.2 μM (CatK:T06 molar ratio of 1:5). However, it does not suppress fluorogenic peptide cleavage and gelatinolysis at a 2500-fold molar excess. Contrary to active site-directed CatK inhibitors, such as odanacatib, T06 suppresses bone resorption in both human and mouse osteoclasts equally well (IC50 value for human and mouse osteoclasts: 237 ± 60 nM and 245 ± 55 nM, respectively) and its antiresorptive activity is fully reversible in both cell types. Moreover, T06 affects neither the metabolic activity of osteoclasts nor osteoclastogenesis. In in vivo studies, 40 mg T06/kg/d given to 12-week-old ovariectomized (OVX) mice for 3 months reduced plasma CTx-1 by 20% and increased osteoblast numbers and plasma P1NP by ∼28% when compared with the OVX control. μCT analysis of T06-treated OVX mice showed a 35% increase in bone mineral density and other femoral trabecular bone parameters when compared with OVX animals. T06 did not alter the number of osteoclasts, had no estrogenic effect on the uterus, did not change plasma estradiol levels, and did not inhibit fibroblast-mediated TGF-ß1 processing or degradation and cognitive functions in OVX mice. This study indicates that the ectosteric inhibitor, T06, is a selective antiresorptive CatK inhibitor that may overcome the shortcomings of side effect–prone active site-directed drugs, which all failed in clinical trials. © 2017 American Society for Bone and Mineral Research.
Redox homeostasis and age‐related deficits in neuromuscular integrity and function
Authors: Sakellariou Giorgos K. , Lightfoot Adam P. , Earl Kate E. , Stofanko Martin , McDonagh Brian
Published: July 2017

Skeletal muscle is a major site of metabolic activity and is the most abundant tissue in the human body. Age‐related muscle atrophy (sarcopenia) and weakness, characterized by progressive loss of lean muscle mass and function, is a major contributor to morbidity and has a profound effect on the quality of life of older people. With a continuously growing older population (estimated 2 billion of people aged >60 by 2050), demand for medical and social care due to functional deficits, associated with neuromuscular ageing, will inevitably increase. Despite the importance of this ‘epidemic’ problem, the primary biochemical and molecular mechanisms underlying age‐related deficits in neuromuscular integrity and function have not been fully determined. Skeletal muscle generates reactive oxygen and nitrogen species (RONS) from a variety of subcellular sources, and age‐associated oxidative damage has been suggested to be a major factor contributing to the initiation and progression of muscle atrophy inherent with ageing. RONS can modulate a variety of intracellular signal transduction processes, and disruption of these events over time due to altered redox control has been proposed as an underlying mechanism of ageing. The role of oxidants in ageing has been extensively examined in different model organisms that have undergone genetic manipulations with inconsistent findings. Transgenic and knockout rodent studies have provided insight into the function of RONS regulatory systems in neuromuscular ageing. This review summarizes almost 30 years of research in the field of redox homeostasis and muscle ageing, providing a detailed discussion of the experimental approaches that have been undertaken in murine models to examine the role of redox regulation in age‐related muscle atrophy and weakness.
Specification of Larval Axes of Partial Embryos in the Temnopleurid Temnopleurus toreumaticus and the Strongylocentroid Hemicentrotus pulcherrimus
Authors: Kitazawa Chisato , Nakano Michihiro , Yamaguchi Tadashi , Miyahara Chisato , Yamanaka Akira
Published: July 2017

Many sea urchins, including the strongylocentroid Hemicentrotus pulcherrimus, produce an amniotic cavity on the left for adult rudiment formation at the late larval stage. In contrast, temnopleurids form a cell mass at the early larval stage instead of an amniotic cavity. Although the mechanisms establishing left–right polarity of the amniotic cavity involve cell–cell interactions and signaling pathways, corresponding pathways for the cell mass are unknown. We analyzed the effects of blastomere isolation on the specification of larval axes in the temnopleurid Temnopleurus toreumaticus and compared them to those in H. pulcherrimus. Blastomere isolation at the two‐ or four‐cell stages in T. toreumaticus disturbed the location of the cell mass and adult rudiment in approximately 10–20% of specimens. In contrast, isolation at the two‐cell stage in H. pulcherrimus caused the left–right polarity to become random. When blastomeres isolated at the two‐cell stage were cultured as pairs, approximately 20% of pairs had atypical polarity in both species. Following isolation at the four‐cell stage, 71.4% of quartets produced larvae with atypical polarity in T. toreumaticus. Thus, cell–cell interaction between two daughter blastomeres after the second cleavage may be involved in the mechanism determining left–right polarity. Dye injection into a blastomere and subsequent observations indicated that the location of the boundary of the first cleavage showed similar patterns in both species. These observations suggest that species‐specific mechanisms establish the larval axes and blastomeres at the two‐ and four‐cell stages redistribute their cytoplasm, forming gradients that establish left–right polarity.
Association of incretin receptors genetic polymorphisms with type 2 diabetes mellitus in Egyptian patients
Authors: Shalaby Sally M. , Zidan Haidy E. , Shokry Amira , Saeed Jehan , El‐Sokkary Rehab H.
Published: July 2017

Background

Incretins have opened a new era in type 2 diabetes mellitus (T2DM) pathogenesis. The present study aimed to assess whether there is an association between GIPR rs2302382, GIPR rs1800437 and GLP‐1R rs367543060 polymorphisms with T2DM or not and also to determine the effect of these polymorphisms on gastric inhibitory polypeptide (GIP) and glucagon‐like peptide‐1 (GLP‐1) levels.

Methods

One hundred and fifty T2DM patients and 150 healthy controls were included in the study. Polymorphisms of GIPR rs1800437, GIPR rs2302382 and GLP‐1R rs367543060 were genotyped using restriction fragment length polymorphism (RFLP)‐polymerase chain reaction (PCR), multiplex allele‐specific PCR and RFLP‐PCR respectively. GIP and GLP levels were measured by an enzyme‐linked immunosorbent assay.

Results

We found a significant association of both the homozygous AA and the minor allele A of GIPR rs2302382 with T2DM. The frequency of haplotype C(rs2302382) G(rs1800437) was significantly higher in controls than in diabetics; odds ratio (95% confidence interval): 1.99 (1.44–2.75) (p < 0.001), whereas the haplotype A(rs2302382) C(rs1800437) was significantly higher in patients than controls. We did not find any association of GLP‐1R rs367543060 polymorphism with T2DM. We found a significant increase in serum total GIP and a significant decrease of GLP‐1 levels in T2DM patients.

Conclusions

We reveal for the first time an association between the GIPR rs2302382 polymorphism and T2DM in Egyptians. Yet, there was no significant association of GIPR rs1800437 or GLP‐1R rs367543060 with T2DM risk. The haplotype A (rs2302382) C (rs1800437) was associated with an increased risk of T2DM. Furthermore, there was a significant increase of GIP and a significant decrease of GLP‐1 levels when diabetic patients were compared with controls. An important finding was that there was a relationship between both GIPR rs2302382 and rs1800437 variants and their cognate ligand levels.
Relation between Polymer Conformational Structure and Dynamics in Linear and Ring Polyethylene Blends
Authors: Jeong Cheol , Douglas Jack F.
Published: July 2017

Atomistic molecular dynamics simulations of ring‐linear polyethylene blends are employed to understand the relationship between chain conformational structure and the melt dynamics of these blends. As observed in previous studies, this study confirms that ring polymers in pure melts do not exhibit screened excluded volume interactions, contrary to linear polymers. Moreover, the average molecular shapes of the rings are quite distinct from both swollen and ideal ring polymers under theta conditions, and instead rather resemble branched polymers with screened binary excluded volume interactions, e.g., percolation clusters. Upon adding linear chains to a melt of pure rings, we find significant swelling of the rings and a corresponding shape change that is qualitatively similar to dissolving rings in a small molecule good solvent. This swelling, arising from altered self‐excluded volume interactions, translates into a large decrease in ring diffusivity, an effect that becomes more amplified when the polymer melt is entangled.
Assessment of rapid growth ventures, an extension of Schwartz and Moon model
Authors: Afik Zvika , Zwilling Eran
Published: July 2017

It is a challenge to incorporate randomness into financial projections that are at the core of new venture assessment. We present a model based on Schwartz and Moon () and apply it to a real firm data. We find that our 10‐year projections conform to the actual realized values. The model allows addressing crucial questions regarding the venture survival, its extreme potential outcomes, and its sensitivity to its parameters. It facilitates identifying risk drivers and assessing potential remedies. To our knowledge, we are the first to propose such a comprehensive stochastic model for risky ventures' simulation and analysis.
An option pricing approach to optimal bidding in construction projects
Authors: Ribeiro João Adelino , Pereira Paulo J. , Brandão Elisio M.
Published: July 2017

Reaching an optimal mark‐up value in the context of construction projects' bidding competitions has been a research topic for more than 40 years. This paper aims to contribute to this debate by applying a real options approach. The proposed model has a pure theoretical nature and is based on a maximization problem, whose outcome is the optimal price, that is, the price that should be included in the bid proposal. The model is later extended to accommodate the existence of penalty costs if the selected bidder refuses to enter into contract. Results reached using a numerical example demonstrate that the optimal price is higher when penalty costs are considered.
Shape derivative of the volume integral operator in electromagnetic scattering by homogeneous bodies
Authors: Sakly Hamdi
Published: July 2017

We study the shape derivative of the strongly singular volume integral operator that describes time‐harmonic electromagnetic scattering from homogeneous medium. We show the existence and a representation of the derivative, and we deduce a characterization of the shape derivative of the solution to the diffraction problem as a solution to a volume integral equation of the second kind.
Detection and quantification of overactive bladder activity in patients: Can we make it better and automatic?
Authors: Niederhauser Thomas , Gafner Elena S. , Cantieni Tarcisi , Grämiger Michelle , Haeberlin Andreas , Obrist Dominik , Burkhard Fiona , Clavica Francesco
Published: July 2017

Aims

To explore the use of time‐frequency analysis as an analytical tool to automatically detect pattern changes in bladder pressure recordings of patients with overactive bladder (OAB). To provide quantitative data on the bladder's non‐voiding activity which could improve the current diagnosis and potentially the treatment of OAB.

Methods

We developed an algorithm, based on time‐frequency analysis, to analyze bladder pressure during the filling phase of urodynamic studies. The algorithm was used to generate a bladder overactivity index (BOI) for a quantitative estimation of the average bladder non‐voiding‐activity. We tested the algorithm with one control group and two groups of patients with OAB symptoms: one group with detrusor overactivity (DO), assessed by an experienced urologist (OAB‐with‐DO group), and another group for which detrusor overactivity was not diagnosed (OAB‐without‐DO group).

Results

The algorithm identified diagnostically significant data on the bladder non‐voiding activity in a specified frequency range. BOI was significantly higher for both OAB groups compared to the control group: the median value of BOI was twice as big in OAB‐without‐DO and more than four times higher in OAB‐with‐DO compared to control group. Moreover the algorithm was successfully tested to detect episodes of detrusor overactivity.

Conclusions

We have shown that a simple algorithm, based on time‐frequency analysis of bladder pressure, may be a promising tool in the clinical setting. The algorithm can provide quantitative data on non‐voiding bladder activity in patients and quantify the changes according to phenotype. Moreover the algorithm can detect DO, showing potential for triggering conditional bladder stimulation.
Nonalcoholic Steatohepatitis is Associated with Cardiac Remodeling and Dysfunction
Authors: Simon Tracey G. , Bamira Daniel G. , Chung Raymond T. , Weiner Rory B. , Corey Kathleen E.
Published: July 2017

Objective

Preliminary data suggest that nonalcoholic fatty liver disease is associated with early heart failure (HF). However, whether nonalcoholic steatohepatitis (NASH) is directly associated with echocardiographic changes in cardiac structure or function remains unknown.

Methods

A retrospective cohort was identified of individuals (N = 65) without known heart disease, undergoing elective bariatric surgery with perioperative liver biopsy, and available recent transthoracic echocardiography (TTE). TTE measures were evaluated by NASH status using correlation coefficients, ANOVA, and linear regression, accounting for cardiometabolic factors.

Results

Median age was 47 years; 22% (n = 14) had NASH. NASH patients had increased median left atrial (LA) volume (28.6 mL/m2 vs. 24.8 mL/m2; P < 0.0001) and left ventricular (LV) mass (82.6 g/m2 vs. 78.6 g/m2; P < 0.0001), indexed for height. NASH was inversely correlated with indices of diastolic function, including septal E′ (r = −0.90 [95% CI: −1.21 to −0.42]; P = 0.020) and E:A (r = −0.31 [95% CI: −0.51 to −0.09]; P = 0.037). In adjusted analyses, NASH remained associated with increased LV mass index (ß1 = 7.16 [SE: 4.95]; P = 0.001) and LA volume index (ß1 = 0.19 [SE: 0.08]; P = 0.001) and reduced lateral and septal E′ (ß1 = −0.91, P = 0.015; ß1 = −0.89, P = 0.047, respectively).

Conclusions

In this bariatric cohort, NASH was associated with changes in myocardial structure and in load‐dependent indices of LV diastolic function, suggestive of subclinical HF.
Papua New Guineans Reconstructing their Histories: The Pacific War Revisited
Authors: Ritchie Jonathan
Published: July 2017

This article discusses the project to record interviews with Papua New Guineans about their experiences of the Pacific War between 1942 and 1945, which was very much a critical juncture in the course of Papua New Guinean history. It examines how Papua New Guineans’ encounters with the War that devastated their land have been portrayed, and suggests that an exploration featuring Papua New Guineans in the telling of their own experiences with the War derives from the argument by the late Epeli Hau'ofa that they should be active participants in the reconstruction of their histories and the creation of their realities.
The Shifting Moralities of Mobile Phones in Lau Communicative Ecologies (Solomon Islands)
Authors: Hobbis Geoffrey
Published: July 2017

In the past decade, digital technologies and especially mobile phones have spread rapidly across the Solomon Islands. This process has been surprising not only in how quickly many Solomon Islanders have become digitally savvy, but also in rapidly emerging moral debates that pit the ability to stay in touch with family and friends against the dangers of immoral behaviour, especially sexual promiscuity, and of malevolent sorcery. Based on a communicative ecology approach, this paper identifies the proliferation of mobile phones as a critical juncture with temporal and spatial ramifications in its double bind. That is, mobile phones are increasingly recognized as needed to maintain social networks, but they are also seen to harbour the potential for accelerating immoral sociality by increasing the potential for privacy.
Experimental study on compression properties and failure mechanism of 3D MWK carbon/epoxy composites at elevated temperatures
Authors: Jiang Nan , Li Dian‐Sen , Yao Qian‐qian , Duan Hong‐wei , Ko Frank
Published: July 2017

The compressive behavior of the 3D MWK carbon/epoxy composites with two fiber architectures were performed in longitudinal and transverse directions at room and elevated temperatures. Macro‐fracture and SEM micrographs were examined to understand the deformation and failure mechanism of 3D MWK carbon/epoxy composites. The results show that the compression properties and failure patterns vary with the temperature, fiber architecture, and loading mode. The compressive stress–strain curves and properties are different in longitudinal and transverse directions. Meanwhile, the properties increase with the increase of fiber orientation angle and decrease significantly with the increase of temperature, especially after 75°C. Moreover, for longitudinal compression, material A [0°/90°/+45°/‐45°] exhibits shear brittle feature and that the delaminating failure at elevated temperatures, while material B[0°/0°/0°/0°] behaves multiple shear fracture at 45°. For transverse compression, material A shows delaminating fracture along 0°, 90°, +45°, −45° fiber layers and material B is the delaminating between 0° fiber layers. At elevated temperatures, the damage of matrix yielding, cracking, and interface debonding become prominent, the composite becomes more softened and attains plasticity. POLYM. COMPOS., 39:E1987–E1999, 2018. © 2018 Society of Plastics Engineers
A study on the photostabilizer additives on the textile fiber reinforced polymer composites: Mechanical, thermal, and physical analysis
Authors: Bodur Mehmet Safa , Bakkal Mustafa , Sonmez Hasret Ece
Published: July 2017

The effect of photostabilizers on the mechanical, thermal, and physical properties of textile fiber reinforced polymer (T‐FRP) composites was investigated. In the first phase of this study, the effect of different concentrations of ultra violet absorber (UVA), hindered amine light stabilizers (HALS) and antioxidants (AOs) into T‐FRP composites for unweathering condition are examined. Mechanical tests were performed as well as differential scanning calorimetry (DSC) analysis for thermal properties. According to test results, there is no significant effect of photostabilizers on the mechanical and thermal properties of the T‐FRP composites. In the second phase of the study, the influence of the photostabilizers on the durability performance of T‐FRP composites is focused under the accelerated UV weathering condition by the help of tensile testing, thermal analysis, and color measurements. According to test results, only about 5% loss in mechanical properties (25% loss for composites without additives) can be observed after 240 h of UV weathering with HALS and UVA addition at adequate concentrations. In addition, AOs can be considered as a strong stabilizer on physical properties with lower color change values. This work shows that the efficiency of the photostabilizers is highly dependent on the type, concentration, and weathering time. POLYM. ENG. SCI., 58:1082–1090, 2018. © 2017 Society of Plastics Engineers
Effect of filler content on the structure‐property behavior of poly(ethylene oxide) based polyurethaneurea‐silica nanocomposites
Authors: Oguz Oguzhan , Simsek Eren , Kosak Soz Cagla , Kasli Heinz Ozge , Yilgor Emel , Yilgor Iskender , Menceloglu Yusuf Z.
Published: July 2017

Poly(ethylene oxide) (PEO) based polyurethaneurea‐silica nanocomposites were prepared by solution blending and characterized by Fourier Transform Infrared Spectroscopy, Scanning Electron Microscopy, Differential Scanning Calorimetry and tensile testing. The colloidal silica nanoparticles with an average size of 50 nm were synthesized by modified Stöber method in isopropanol. Silica particles were incorporated into three cycloaliphatic polyurethaneurea (PUs) copolymers based on PEO oligomers with molecular weights of 2,000, 4,600, and 8,000 g/mol. Hard segment content of PUs was constant at 30% by weight. Silica content of the PU nanocomposites varied between 1 and 20% by weight. Soft segment (SS) glass transition and melting temperatures slightly increased with increasing filler content for all the copolymers. Degree of SS crystallinity first increased with 1% silica incorporation and subsequently decreased by further silica addition. Elastic modulus and tensile strengths of PU copolymers gradually increased with increasing amount of the silica filler. Elongation at break values gradually decreased in PEO‐2000 based PU copolymer with increasing silica content, whereas no significant change was observed in PUs based on PEO‐4600 and PEO‐8000. Enhancement in tensile properties of the materials was mainly attributed to the homogeneous distribution of silica filler in polymer matrices and strong polymer‐filler interactions. POLYM. ENG. SCI., 58:1097–1107, 2018. © 2017 Society of Plastics Engineers
Enhanced fracture toughness of nanostructured carbon‐fiber reinforced poly(urethane‐isocyanurate) composites at low concentrations
Authors: Chiacchiarelli Leonel M. , Petrucci Roberto , Torre Luigi
Published: July 2017

Carbon fiber reinforced poly(urethane‐isocyanurate)‐nanosilica composites CF‐(PUI‐NS) were manufactured by means of the vacuum‐assisted resin transfer moulding technique (VARTM) at very low NS concentrations (0–4 wt%). The high strain to failure of the PUI matrix (>7%) affected tensile tests by CF reorientation. Both the tensile strength and strain to failure were highly dependent on its kinematics. CF(PUI‐NS) caused an increase of the static toughness with a maximum improvement of tensile strain to failure and modulus of +28.8% and +39% at 1 wt% and 2 wt% of NS, respectively. The interlaminar shear strength (GIC) of the composites showed both a deterioration of −12.9% and an improvement of +9.9% for NS concentrations of 1 wt% and 4 wt%, respectively. Regardless of the GIC value, all of the composites prepared with NS presented secondary maxima of the force versus displacement plots, indicating a substantial arrest of the crack propagation velocity after delamination started. Fractographic analysis revealed several features, such as fiber pull‐out, bridging as well as river patterns whereas the composites prepared with NS behaved in a more ductile fashion due to the presence of river patterns and a reduced fiber pull‐out. POLYM. ENG. SCI., 58:1241–1250, 2018. © 2017 Society of Plastics Engineers
Control of composite thin film made in an Ar/isopropanol/TiO2 nanoparticles dielectric barrier discharge by the excitation frequency
Authors: Brunet Paul , Rincón Rocío , Martinez Jean‐Michel , Matouk Zineb , Fanelli Fiorenza , Chaker Mohamed , Massines Françoise
Published: July 2017

The synthesis of composites thin films made by injecting an aerosol suspension of 20 nm‐size TiO2 nanoparticles (NPs) and isopropanol (IPA) in a filamentary argon Dielectric Barrier Discharge (DBD) is studied as a function of the DBD frequency from 1 to 50 kHz. The plasma is modulated to get homogeneous coatings. The deposition rate and morphology of the composite thin films are determined from SEM images of both surface and cross section. Their chemical composition is investigated by XPS, Raman spectroscopy and FTIR measurements. The structural composition of the NPs is examined by XRD. All the deposited composites show the chemical signature of the NPs as well as of the polymer‐like coating resulting from the plasma polymerization of IPA. No mixed phase is observed and the sizes of the NPs as well as of their aggregates are not affected by the plasma. With this method aerosol droplets are evaporated before entering the plasma and the NPs inside a same droplet are aggregated. Results show that the DBD frequency controls the composite composition by independently influencing the NPs transport and the matrix growth rate. At 1 kHz, the coating is essentially made of NPs with a low carbon coating. From 1 to 50 kHz, the Ti/C ratio is divided by two orders of magnitude. As the frequency increases the quantity of NPs decreases and since 10 kHz the matrix thickness increases. The decrease of the NPs is explained by the numerical modeling of the NPs trajectory. It is found that from 10 to 1 kHz, the lower is the frequency, the higher is the transport of the NPs to the surface due to the electrostatic force. On the other hand the matrix growth rate increases from almost zero at 10 kHz up to 19 nm · min−1 at 50 kHz because of the linear increases of the DBD power with the frequency.
Metal–Polymer Hybrid Nanoparticles for Correlative High‐Resolution Light and Electron Microscopy
Authors: Reifarth Martin , Preußger Elisabeth , Schubert Ulrich S. , Heintzmann Rainer , Hoeppener Stephanie
Published: July 2017

The combination of fluorescence microscopy and electron microscopy promises a deeper insight into the ultrastructural features of cell organelles, e.g., after drug administration. Both methods complement each other and provide, as a correlative approach, a keen insight into the fate of nanoparticles within the cell. Moreover, it represents a promising tool to determine alterations of the cellular environment as a response to particle uptake. However, the availability of suitable correlative markers is mandatory for such correlative approaches. In this contribution, the utilization of poly(ethylene imine) based metal–polymer hybrid particles labeled with small gold nanoparticles and Rhodamine B facilitating the observation of the particles by means of fluorescence as well as by transmission electron microscopy is suggested. Correlative light and electron microscopy is used to study uptake and intracellular fusion processes of endosomal/lysosomal structures.
A subset of high Gleason grade prostate carcinomas contain a large burden of prostate cancer syndecan‐1 positive stromal cells
Authors: Sharpe Benjamin , Alghezi Dhafer A. , Cattermole Claire , Beresford Mark , Bowen Rebecca , Mitchard John , Chalmers Andrew D.
Published: July 2017

Background

There is a pressing need to identify prognostic and predictive biomarkers for prostate cancer to aid treatment decisions in both early and advanced disease settings. Syndecan‐1, a heparan sulfate proteoglycan, has been previously identified as a potential prognostic biomarker by multiple studies at the tissue and serum level. However, other studies have questioned its utility.

Methods

Anti‐Syndecan‐1 immunohistochemistry was carried out on 157 prostate tissue samples (including cancerous, adjacent normal tissue, and non‐diseased prostate) from three independent cohorts of patients. A population of Syndecan‐1 positive stromal cells was identified and the number and morphological parameters of these cells quantified. The identity of the Syndecan‐1‐positive stromal cells was assessed by multiplex immunofluorescence using a range of common cell lineage markers. Finally, the burden of Syndecan‐1 positive stromal cells was tested for association with clinical parameters.

Results

We identified a previously unreported cell type which is marked by Syndecan‐1 expression and is found in the stroma of prostate tumors and adjacent normal tissue but not in non‐diseased prostate. We call these cells Prostate Cancer Syndecan‐1 Positive (PCSP) cells. Immunofluorescence analysis revealed that the PCSP cell population did not co‐stain with markers of common prostate epithelial, stromal, or immune cell populations. However, morphological analysis revealed that PCSP cells are often elongated and displayed prominent lamellipodia, suggesting they are an unidentified migratory cell population. Analysis of clinical parameters showed that PCSP cells were found with a frequency of 20‐35% of all tumors evaluated, but were not present in non‐diseased normal tissue. Interestingly, a subset of primary Gleason 5 prostate tumors had a high burden of PCSP cells.

Conclusions

The current study identifies PCSP cells as a novel, potentially migratory cell type, which is marked by Syndecan‐1 expression and is found in the stroma of prostate carcinomas, adjacent normal tissue, but not in non‐diseased prostate. A subset of poor prognosis high Gleason grade 5 tumors had a particularly high PCSP cell burden, suggesting an association between this unidentified cell type and tumor aggressiveness.
A tale of two tails: The importance of unstructured termini in the aggregation pathway of β2‐microglobulin
Authors: Loureiro Rui J. S. , Vila‐Viçosa Diogo , Machuqueiro Miguel , Shakhnovich Eugene I. , Faísca Patricia F. N.
Published: July 2017

The identification of intermediate states for folding and aggregation is important from a fundamental standpoint and for the design of novel therapeutic strategies targeted at conformational disorders. Protein human β2‐microglobulin (HB2m) is classically associated with dialysis‐related amyloidosis, but the single point mutant D76N was recently identified as the causative agent of a hereditary systemic amyloidosis affecting visceral organs. Here, we use D76N as a model system to explore the early stage of the aggregation mechanism of HB2m by means of an integrative approach framed on molecular simulations. Discrete molecular dynamics simulations of a structured‐based model predict the existence of two intermediate states populating the folding landscape. The intermediate I1 features an unstructured C‐terminus, while I2, which is exclusively populated by the mutant, exhibits two unstructured termini. Docking simulations indicate that I2 is the key species for aggregation at acidic and physiological pH contributing to rationalize the higher amyloidogenic potential of D76N relative to the wild‐type protein and the ΔN6 variant. The analysis carried out here recapitulates the importance of the DE‐loop in HB2m self‐association at a neutral pH and predicts a leading role of the C‐terminus and the adjacent G‐strand in the dimerization process under acidic conditions. The identification of aggregation hot‐spots is in line with experimental results that support the importance of Phe56, Asp59, Trp60, Phe62, Tyr63, and Tyr66 in HB2m amyloidogenesis. We further predict the involvement of new residues such as Lys94 and Trp95 in the aggregation process.
Antiproliferative Activity of Phenylpropanoids Isolated from Lagotis brevituba Maxim
Authors: Xiang Yuan , Jing Zhao , Haixia Wang , Ruitao Yu , Huaixiu Wen , Zenggen Liu , Lijuan Mei , Yiping Wang , Yanduo Tao
Published: July 2017

The aim of the present study was to evaluate the antiproliferative effect of phenylpropanoids isolated from the n‐BuOH‐soluble fraction of an ethanolic extract of Lagotis brevituba Maxim. The phenylpropanoids were identified as echinacoside, lagotioside, glucopyranosyl(1–6)martynoside, plantamoside, and verbascoside. Three of the compounds, lagotioside, glucopyranosyl(1–6)martynoside, and plantamoside, were isolated from L. brevituba for the first time. The antiproliferative activity of the isolates was evaluated in human gastric carcinoma (MGC‐803), human colorectal carcinoma (HCT116), human hepatocellar carcinoma (HepG2), and human lung cancer (HCT116) cells using an 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay. Plantamoside showed promising activity against MGC‐803 cells, with a half maximal inhibitory concentration value of 37.09 μM. The mechanism of the pro‐apoptosis effect of plantamoside was then evaluated in MGC‐803 cells. Changes in cell morphology, including disorganization of the architecture of actin microfilaments and formation of apoptotic bodies, together with cell cycle arrest in G2/M phases, were observed after treatment of plantamoside. The antiproliferative and pro‐apoptotic effects were associated with a decrease in the ratio of Bcl‐2/Bax and reduced mitochondrial membrane potential, which was accompanied by the release of reactive oxygen species and Ca2+ into the cytoplasm. Taken together, the results indicated that plantamoside promotes apoptosis via a mitochondria‐dependent mechanism. Copyright © 2017 John Wiley & Sons, Ltd.
Recursive multivariate principal‐monotonicity inferential climate downscaling
Authors: Cheng Guanhui , Huang Guohe , Dong Cong , Zhu Jinxin , Zhou Xiong , Yao Yao
Published: July 2017

A recursive multivariate principal‐monotonicity inferential downscaling approach (ReMPMID) is proposed for climate downscaling under complexities of data uncertainties, nonlinear predictor–predictand correspondences, predictand dependencies, non‐normal distributions, spatial homogeneities, and temporal non‐stationarities. This approach is applied to the Athabasca River Basin (ARB) to verify methodological effectiveness. Many findings are revealed. For instance, ReMPMID may enable improvement of statistical downscaling reliability in comparison with selected existing approaches under these complexities at least for the ARB. The overall accuracies of ReMPMID are relatively high for temperature, while being acceptable for precipitation at the multi‐year scale. This approach may overestimate temperature in spring and winter and precipitation in summer and autumn while underestimating temperature in summer and autumn and precipitation in spring and winter to a relatively small extent. The modelling accuracies are not sensitive to one parameter (i.e. the statistical significance level) and significantly vary with another parameter (i.e. the minimum partition row number, Nmin). The calibration accuracies decrease with the climbing of Nmin and there is not a significant monotonic relationship between Nmin and the verification accuracies. The optimal value of Nmin varies with grids and predictands and shows higher uncertainty for temperature compared with precipitation. The uncertainties in ReMPMID simulations increase from summer, autumn, spring to winter for temperature and from winter, spring, autumn to summer for precipitation. These findings are helpful for gaining insights into ReMPMID and the regional climate in the ARB or neighbouring regions.
Optimal robust and tolerance design for computer experiments with mixture proportion inputs
Authors: Han Mei , Tan Matthias Hwai Yong
Published: July 2017

Computer experiments often have inputs that are proportions/fractions of components in a mixture. In these mixture computer experiments, it can be of interest to perform robust and tolerance design on the mixture proportions since the proportions are subjected to noise variations. Traditionally, manufacturing of mixture products is controlled via interval tolerances for mixture amounts. In this paper, an optimal tolerance region for proportions, which gives optimal quality cost among all possible tolerance regions for mixture proportions with the same acceptance probability, is proposed for integrated parameter and tolerance design in mixture computer experiments. Real examples are given to demonstrate the improvements that can be achieved with the optimal tolerance region.
Doubly robust inference for targeted minimum loss–based estimation in randomized trials with missing outcome data
Authors: Díaz Iván , van der Laan Mark J.
Published: July 2017

Missing outcome data is a crucial threat to the validity of treatment effect estimates from randomized trials. The outcome distributions of participants with missing and observed data are often different, which increases bias. Causal inference methods may aid in reducing the bias and improving efficiency by incorporating baseline variables into the analysis. In particular, doubly robust estimators incorporate 2 nuisance parameters: the outcome regression and the missingness mechanism (ie, the probability of missingness conditional on treatment assignment and baseline variables), to adjust for differences in the observed and unobserved groups that can be explained by observed covariates. To consistently estimate the treatment effect, one of these nuisance parameters must be consistently estimated. Traditionally, nuisance parameters are estimated using parametric models, which often precludes consistency, particularly in moderate to high dimensions. Recent research on missing data has focused on data‐adaptive estimation to help achieve consistency, but the large sample properties of such methods are poorly understood. In this article, we discuss a doubly robust estimator that is consistent and asymptotically normal under data‐adaptive estimation of the nuisance parameters. We provide a formula for an asymptotically exact confidence interval under minimal assumptions. We show that our proposed estimator has smaller finite‐sample bias compared to standard doubly robust estimators. We present a simulation study demonstrating the enhanced performance of our estimators in terms of bias, efficiency, and coverage of the confidence intervals. We present the results of an illustrative example: a randomized, double‐blind phase 2/3 trial of antiretroviral therapy in HIV‐infected persons.
Inference on network statistics by restricting to the network space: applications to sexual history data
Authors: Goyal Ravi , De Gruttola Victor
Published: July 2017

Analysis of sexual history data intended to describe sexual networks presents many challenges arising from the fact that most surveys collect information on only a very small fraction of the population of interest. In addition, partners are rarely identified and responses are subject to reporting biases. Typically, each network statistic of interest, such as mean number of sexual partners for men or women, is estimated independently of other network statistics. There is, however, a complex relationship among networks statistics; and knowledge of these relationships can aid in addressing concerns mentioned earlier. We develop a novel method that constrains a posterior predictive distribution of a collection of network statistics in order to leverage the relationships among network statistics in making inference about network properties of interest. The method ensures that inference on network properties is compatible with an actual network. Through extensive simulation studies, we also demonstrate that use of this method can improve estimates in settings where there is uncertainty that arises both from sampling and from systematic reporting bias compared with currently available approaches to estimation. To illustrate the method, we apply it to estimate network statistics using data from the Chicago Health and Social Life Survey. Copyright © 2017 John Wiley & Sons, Ltd.
Empirical likelihood‐based confidence intervals for mean medical cost with censored data
Authors: Jeyarajah Jenny , Qin Gengsheng
Published: July 2017

In this paper, we propose empirical likelihood methods based on influence function and jackknife techniques for constructing confidence intervals for mean medical cost with censored data. We conduct a simulation study to compare the coverage probabilities and interval lengths of our proposed confidence intervals with that of the existing normal approximation‐based confidence intervals and bootstrap confidence intervals. The proposed methods have better finite‐sample performances than existing methods. Finally, we illustrate our proposed methods with a relevant example.
Nickel Diselenide Ultrathin Nanowires Decorated with Amorphous Nickel Oxide Nanoparticles for Enhanced Water Splitting Electrocatalysis
Authors: Li Haoyi , Chen Shuangming , Lin Haifeng , Xu Xiaobin , Yang Haozhou , Song Li , Wang Xun
Published: July 2017

Well‐designed hybrid materials based on noble metal‐free elements have great potential to generate hydrogen (H2) and oxygen (O2) sustainably via overall water splitting for developing practical energy‐related technologies. Herein, an accessible method is presented to synthesize nickel diselenide (NiSe2) ultrathin nanowires decorated with amorphous nickel oxide nanoparticles (NiOx NPs) as multifunctional electrocatalysts (NSWANs) for hydrogen and oxygen evolution reaction (HER and OER). The NSWANs exhibit quite low HER and OER overpotentials of 174 and 295 mV, respectively, holding the current density of 20 mA cm−2 for 24 h continuous operations in alkaline media. Meanwhile, a cell voltage of 1.547 V at the current density of 10 mA cm−2 for overall water splitting has been achieved by the NSWANs for the practical application, which could maintain fascinating activity of 20 mA cm−2 for 72 h without degradation. The decorated NiOx NPs not only prevent the NiSe2 from further oxidation but also expose requisite active sites for electrocatalytic process. It is believed that this study may provide a valuable strategy to design high‐efficiency electrocatalysts and expand the applications of selenide‐based materials.
Boundary condition effects on RC frames internally reinforced by FRP bars
Authors: Confrere Adeline , Ferrier Emmanuel , Michel Laurent , Chanvillard Gilles
Published: July 2017

This paper discusses RC beam frames made of and internally reinforced by Fibers‐Reinforced Polymer (FRP). An experimental study is combined with analytical modeling to analyze the mechanical response of the Reinforced Concrete frames. The paper also studies the enhancement of the load displacement mechanical response of RC beams with internally reinforced FRP bars that can be modified with continuous boundary conditions, different from the case when using simple support beams. Due to the initial embedded boundary conditions, the deflections at the mid‐span of the beams are reduced. A simplified model for an RC frame that is internally reinforced by FRP is proposed to predict the load–displacement curve.
A modified response spectrum analysis procedure to determine nonlinear seismic demands of high‐rise buildings with shear walls
Authors: Najam Fawad Ahmed , Warnitchai Pennung
Published: July 2017

The standard response spectrum analysis (RSA) procedure prescribed in various design codes is commonly used by practicing engineers to determine the seismic demands for structural design purpose. In this procedure, the elastic force demands of all significant vibration modes are first combined and then reduced by a response modification factor (R) to get the inelastic design demands. Recent studies, however, have shown that the response of higher vibration modes may experience much lower level of nonlinearity, and therefore, it may not be appropriate to reduce their demand contributions by the same factor. In this study, a modified RSA procedure based on equivalent linearization concept is presented. The underlying assumptions are that the nonlinear seismic demands can be approximately obtained by summing up the individual modal responses and that the responses of each vibration mode can be approximately represented by those of an equivalent linear SDF system. Using 3 high‐rise buildings with reinforced concrete shear walls (20‐, 33‐, and 44‐story high), the accuracy of this procedure is examined. The inelastic demands computed by the nonlinear response history analysis procedure are used as benchmark. The modified RSA procedure is found to provide reasonably accurate demand estimations for all case study buildings.
Predictor‐based iterative neural dynamic surface control for three‐phase voltage source PWM rectifier
Authors: Diao Liang , Wang Dan , Peng Zhouhua , Guo Lei
Published: July 2017

This paper addresses the control problem of a three‐phase voltage source pulse width modulation rectifier in the presence of parametric uncertainties and external time‐varying disturbances. An adaptive controller is designed by combining a modified dynamic surface control method and a predictor‐based iterative neural network control algorithm. Especially, neural networks with iterative update laws based on prediction errors are employed to identify the lumped uncertainties. Besides, a finite‐time‐convergent differentiator, instead of a first‐order filter, is used to obtain the time derivative of the virtual control law. Using a Lyapunov–Krasovskii functional, it is proved that all signals in the closed‐loop system are ultimately uniformly bounded. Both simulation and experimental studies are provided to show the effectiveness of the proposed approach. © 2017 Institute of Electrical Engineers of Japan. Published by John Wiley & Sons, Inc.
Supporting the Literacy Development of Students Who Are Deaf/Hard of Hearing in Inclusive Classrooms
Authors: Dostal Hannah , Gabriel Rachael , Weir Joan
Published: July 2017

Students who are deaf or hard of hearing present unique opportunities and challenges for literacy instruction in mainstream classrooms. By addressing the specific needs of this diverse student community, teachers are given the chance to sharpen instruction and create learning opportunities for the entire class. The authors discuss two easy‐to‐follow principles that will increase literacy outcomes for students who are deaf or hard of hearing and all other learners by making content and thinking visible and optimizing access to the language and thoughts of all readers and writers. Practical tips and strategies are based on research and experience across a range of settings, including schools for the deaf with signing students, and mainstream classrooms with students who use listening and spoken language are included.
Safety and Feasibility of Umbilical Diverting Loop Ileostomy for Patients with Rectal Tumor
Authors: Miyo Masaaki , Takemasa Ichiro , Hata Taishi , Mizushima Tsunekazu , Doki Yuichiro , Mori Masaki
Published: July 2017

Background

Fashioning an ileostomy in the umbilicus and combining the trauma from extraction of colorectum with that from ileostomy should be less invasive and lead to improved cosmetic outcomes. However, there are only a few reports regarding umbilical ileostomy.

Methods

We retrospectively collected data for 121 consecutive patients with rectal tumor who underwent elective laparoscopic rectal resection with diverting loop ileostomy between 2010 and 2015 at Osaka University Hospital, Japan. The safety and feasibility of umbilical diverting loop ileostomy and its influence on stoma care were investigated.

Results

A total of 83 patients were included in this study; of these, 30 underwent umbilical diverting loop ileostomy and 53 underwent conventional diverting loop ileostomy, which was created in the right lower quadrant of the abdomen. The umbilical and conventional groups showed similar rates of postoperative and stoma‐related complications (26.7 vs. 32.1%, p = 0.804 and 3.3 vs. 3.8%, p = 1.000, respectively). Level of parastomal dermatitis was evaluated by DET score at three time points (stoma self‐management establishment, first outpatient review post‐discharge, and just before stoma closure). DET scores at any time points did not differ significantly between the two groups.

Conclusions

Umbilical diverting loop ileostomy is comparable to conventional ileostomy with regard to safety and feasibility. Our methods for umbilical ileostomy using the umbilical skin flap were less invasive and did not have a negative impact on stoma care and parastomal dermatitis. Umbilical ileostomy may be a promising alternative to conventional ileostomy in selected cases.