bluuebunny/crossref_metadata_2025 huggingface dataset:
Adenovirus E4-ORF1 Dysregulates Epidermal Growth Factor and Insulin/Insulin-Like Growth Factor Receptors To Mediate Constitutive Myc Expression
Authors: Kong Kathleen , Kumar Manish , Taruishi Midori , Javier Ronald T.
Published: August 2015

The E4-ORF1 protein encoded by human adenovirus stimulates viral replication in human epithelial cells by binding and activating cellular phosphatidylinositol 3-kinase (PI3K) at the plasma membrane and cellular Myc in the nucleus. In this study, we showed that E4-ORF1 hijacks the tyrosine kinase activities of cellular epidermal growth factor receptor (EGFR) and insulin receptor (InsR)/insulin-like growth factor receptor 1 (IGF1R), as well as the lipid kinase activity of PI3K, to mediate constitutive Myc protein expression. We additionally demonstrated that EGFR contributes to constitutive Myc expression through the capacity of E4-ORF1 to induce ligand-independent EGFR activation and stimulation of the Ras/Mek/Erk pathway, the latter activity of which was conserved by human adenoviruses. Results further suggested that EGFR normally forms a complex with the cellular PDZ protein Discs Large 1 (Dlg1), a component of the Dlg1:E4-ORF1:PI3K ternary complex that mediates E4-ORF1-induced PI3K activation, and that E4-ORF1 binds the Dlg1:EGFR complex and promotes the association of EGFR with InsR and IGF1R. In addition to its role in constitutive Myc expression, InsR/IGF1R also negatively regulates EGFR autophosphorylation and EGFR-mediated Ras/Mek/Erk signaling, and data suggested that E4-ORF1 binding to Dlg1 antagonizes these activities. Collectively, our findings suggest that in human epithelial cells, E4-ORF1 targets EGFR, InsR/IGF1R, and PI3K at the plasma membrane to activate cytosolic signaling pathways that sustain Myc protein levels in the nucleus. We postulate that E4-ORF1-induced constitutive Myc expression functions to ensure the formation of nuclear E4-ORF1:Myc complexes, which have been shown to activate Myc and to enhance adenovirus replication.

IMPORTANCE
While human adenoviruses primarily produce self-limited acute infections in humans, these agents are associated with life-threatening diseases in immunocompromised patients and in otherwise healthy individuals infected with certain virulent serotypes. The adenovirus E4-ORF1 protein enhances viral replication by activating the cellular lipid kinase PI3K and the cellular transcription factor Myc. Here we report that E4-ORF1 usurps the functions of the cellular tyrosine kinase receptors EGFR and InsR
/
IGF1R, as well as PI3K, to sustain Myc protein expression in cells. Furthermore, sustained Myc expression depended on E4-ORF1-induced ligand-independent EGFR activation that stimulated Ras/Mek/Erk signaling, a function found to be conserved by human adenoviruses. Given the established roles of PI3K, the Ras/Mek/Erk pathway, and Myc in the adenovirus life cycle, our findings may aid in the development of safer, more effective therapeutic strategies to treat severe adenovirus infections as well as improved adenovirus vectors for use in vaccination and gene and cancer therapy.
A Molecular Staple: D-Loops in the I Domain of Bacteriophage P22 Coat Protein Make Important Intercapsomer Contacts Required for Procapsid Assembly
Authors: D'Lima Nadia G. , Teschke Carolyn M.
Published: August 2015

Bacteriophage P22, a double-stranded DNA (dsDNA) virus, has a nonconserved 124-amino-acid accessory domain inserted into its coat protein, which has the canonical HK97 protein fold. This I domain is involved in virus capsid size determination and stability, as well as protein folding. The nuclear magnetic resonance (NMR) solution structure of the I domain revealed the presence of a D-loop, which was hypothesized to make important intersubunit contacts between coat proteins in adjacent capsomers. Here we show that amino acid substitutions of residues near the tip of the D-loop result in aberrant assembly products, including tubes and broken particles, highlighting the significance of the D-loops in proper procapsid assembly. Using disulfide cross-linking, we showed that the tips of the D-loops are positioned directly across from each other both in the procapsid and the mature virion, suggesting their importance in both states. Our results indicate that D-loop interactions act as “molecular staples” at the icosahedral 2-fold symmetry axis and significantly contribute to stabilizing the P22 capsid for DNA packaging.

IMPORTANCE
Many dsDNA viruses have morphogenic pathways utilizing an intermediate capsid, known as a procapsid. These procapsids are assembled from a coat protein having the HK97 fold in a reaction driven by scaffolding proteins or delta domains. Maturation of the capsid occurs during DNA packaging. Bacteriophage HK97 uniquely stabilizes its capsid during maturation by intercapsomer cross-linking, but most virus capsids are stabilized by alternate means. Here we show that the I domain that is inserted into the coat protein of bacteriophage P22 is important in the process of proper procapsid assembly. Specifically, the I domain allows for stabilizing interactions across the capsid 2-fold axis of symmetry via a D-loop. When amino acid residues at the tip of the D-loop are mutated, aberrant assembly products, including tubes, are formed instead of procapsids, consequently phage production is affected, indicating the importance of stabilizing interactions during the assembly and maturation reactions.
Viral Source-Independent High Susceptibility of Dendritic Cells to Human T-Cell Leukemia Virus Type 1 Infection Compared to That of T Lymphocytes
Authors: Alais Sandrine , Mahieux Renaud , Dutartre Hélène
Published: August 2015

Human T-cell leukemia virus type 1 (HTLV-1)-infected CD4
+
T cells and dendritic cells (DCs) are present in peripheral blood from HTLV-1 carriers. While T-cell infection requires cell-cell contact, DCs might be infected with cell-free virus, at least
in vitro
. However, a thorough comparison of the susceptibilities of the two cell types to HTLV-1 infection using cell-associated and cell-free viral sources has not been performed. We first determined that human primary monocyte-derived dendritic cells (MDDCs) were more susceptible to HTLV-1 infection than their autologous lymphocyte counterparts after contact with chronically infected cells. Next, a comparison of infection efficiency using nonconcentrated or concentrated supernatants from infected cells as well as purified viral biofilm was performed. Integrated provirus was found after exposure of MDDCs or primary lymphocytes to viral biofilm but not to a viral supernatant. Using a large series of primary cell samples (
n
= 21), we demonstrated a higher proviral load in MDDCs exposed to viral biofilm than in lymphocytes. This higher susceptibility is correlated to a higher expression of neuropilin-1 on MDDCs than on autologous activated T lymphocytes. Moreover, we show that MDDCs infected with viral biofilm can transmit the virus to lymphocytes. In conclusion, MDDCs are more susceptible to HTLV-1 infection than autologous lymphocytes
in vitro
, supporting a model in which DC infection might represent an important step during primo-infection
in vivo
.

IMPORTANCE
HTLV-1 is able to infect several cell types, but viral DNA is mainly found in T lymphocytes
in vivo
. This supports a model in which T lymphocytes are the main target of infection. However, during the primo-infection of new individuals, incoming viruses might first encounter dendritic cells (DCs), the specialized immune cells responsible for the antiviral response of the host. HTLV-1 cell-free purified viruses can infect dendritic cells
in vitro
, while T-cell infection is restricted to cell-to-cell transmission. In order to understand the sequence of HTLV-1 dissemination, we undertook a direct comparison of the susceptibilities of the two cell types using cell-associated and cell-free viral sources. We report here that MDDCs are more susceptible to HTLV-1 infection than autologous lymphocytes
in vitro
and are able to efficiently transmit the virus to lymphocytes. Our results suggest that DCs may represent a true viral reservoir, as the first cell type to be infected
in vivo
.
Infectious Diseases at High Altitude
Authors: Basnyat Buddha , Starling Jennifer M.
Published: August 2015

Travel to elevations above 2,500 m is an increasingly common activity undertaken by a diverse population of individuals. These may be trekkers, climbers, miners in high-altitude sites in South America, and more recently, soldiers deployed for high-altitude duty in remote areas of the world. What is also being increasingly recognized is the plight of the millions of pilgrims, many with comorbidities, who annually ascend to high-altitude sacred areas. There are also 400 million people who reside permanently in high mountain ranges, which cover one-fifth of the Earth’s surface. Many of these high-altitude areas are in developing countries, for example, the Himalayan range in South Asia. Although high-altitude areas may not harbor any specific infectious disease agents, it is important to know about the pathogens encountered in the mountains to be better able to help both the ill sojourner and the native high-altitude dweller. Often the same pathogens prevalent in the surrounding lowlands are found at high altitude, but various factors such as immunomodulation, hypoxia, poor physiological adaptation, and harsh environmental stressors at high altitude may enhance susceptibility to these pathogens. Against this background, various gastrointestinal, respiratory, dermatological, neurological, and other infections encountered at high altitude are discussed.
Broad-based molecular autopsy: a potential tool to investigate the involvement of subtle cardiac conditions in sudden unexpected death in infancy and early childhood
Authors: Santori Montserrat , Blanco-Verea Alejandro , Gil Rocio , Cortis Judith , Becker Katrin , Schneider Peter M , Carracedo Angel , Brion Maria
Published: August 2015

Objectives

Sudden unexplained death in children is a tragic and traumatic event, often worsened when the cause of death cannot be determined. This work aimed to investigate the presence of putative pathogenic genetic variants in a broad spectrum of cardiomyopathy, channelopathy and aortic disease associated genes that may have increased these children's vulnerability to sudden cardiac death.

Design

We performed molecular autopsy of 41 cases of sudden unexplained death in infants and children through massive parallel sequencing of up to 86 sudden cardiac death-related genes. Multiple in silico analyses were conducted together with a thorough review of the literature in order to prioritise the putative pathogenic variants.

Results

A total of 63 variants in 35 cases were validated. The largest proportion of these variants is located within cardiomyopathy genes although this would have been more expected of channelopathy gene variants. Subtle microscopic features of heart tissue may indicate the presence of an early onset cardiomyopathy as a predisposing condition to sudden unexpected death in some individuals.

Conclusions

Next-generation sequencing technologies reveal the existence of a wide spectrum of rare and novel genetic variants in sarcomere genes, compared with that of cardiac ion channels, in sudden unexplained death in infants and children. Our findings encourage further investigation of the role of early onset inherited cardiomyopathies and other diseases involving myocardial dysfunction in these deaths. Early detection of variants in these individuals could help to unmask subtle forms of disease within their relatives, who would eventually benefit from better counselling about their genetic history.
High-risk percutaneous coronary intervention in a patient with a single coronary artery presenting as STEMI and cardiogenic shock
Authors: Abdelsalam Murad , Krishnan Mrinalini , Banga Sandeep , Bachinsky William B
Published: August 2015

Cardiogenic shock due to ST elevation myocardial infarction in a patient with a single coronary artery involving the sole vessel is a rare presentation. This can be clinically and angiographically challenging. Proper recognition of the topography of diseased vessels and a systematic guarded approach can lead to procedural success. We report a case of an 81-year-old woman who presented with chest pain followed by a near syncope associated with an acute myocardial infarction. Coronary angiography revealed a single proximally occluded right coronary artery and an anomalous left main coronary artery (originating from the proximal right coronary artery) and occluded distal left circumflex artery. The right coronary artery was successfully stented following predilation without compromising the anomalous left main origin. The flow in the chronically occluded left circumflex artery (originating from the anomalous left main) which was depended on the retrograde supply from right coronary artery through collaterals, was also re-established.
The woman without a history
Authors: Horton Joshua Dean , Mittl Gregory , Thorp Michael , Mitnick Robin
Published: August 2015

The differential diagnosis for altered mental status (AMS) is broad and aetiological pathologies can arise from nearly all organs and body systems. Further complicating the matter, the altered patient is poorly suited to provide a comprehensive and accurate historical account. Thus, the physician must rely on collateral information, laboratories and imaging, and their own clinical suspicion. We present the case of a 75-year-old woman, found prone in her home with AMS, who was unable to provide a history. As her hospital stay evolved, we were forced to consider the entire breadth of possible causes of AMS. Eventually, the patient was found to have cerebral venous thrombosis, the significant extent of which is rarely reported. During the course of caring for the patient, we were reminded of the importance of remaining unbiased and unanchored while attempting to identify the source of the patient's ailment.
Renal cell carcinoma presenting as an upper gastrointestinal bleeding
Authors: Mohamed Mohamed Osama , Al-Rubaye Sinan , Reilly Ian William , McGoldrick Stephen
Published: August 2015

An 80-year-old man presented with melaena and anaemia of 1 week duration. This was associated with shortness of breath and an indigestion-type pain for the preceding 8 weeks. General physical examination revealed epigastric tenderness, but an otherwise soft abdomen with no organomegaly. The patient had a gastroscopy, showing a polypoidal lesion in the second part of duodenum (D2) as the bleeding point, which was managed with epinephrine injection and endoclips. This was followed by CT of the abdomen, revealing a lobulated 8 cm mass arising from the lower pole of the right kidney and invading the duodenum. The case report aims to acknowledge the possibility of direct duodenal involvement in renal cell carcinoma, which is a rare occurrence.
Algorithms for personalized therapy of type 2 diabetes: results of a web-based international survey
Authors: Gallo Marco , Mannucci Edoardo , De Cosmo Salvatore , Gentile Sandro , Candido Riccardo , De Micheli Alberto , Di Benedetto Antonino , Esposito Katherine , Genovese Stefano , Medea Gerardo , Ceriello Antonio
Published: August 2015

Objective

In recent years increasing interest in the issue of treatment personalization for type 2 diabetes (T2DM) has emerged. This international web-based survey aimed to evaluate opinions of physicians about tailored therapeutic algorithms developed by the Italian Association of Diabetologists (AMD) and available online, and to get suggestions for future developments. Another aim of this initiative was to assess whether the online advertising and the survey would have increased the global visibility of the AMD algorithms.

Research design and methods

The web-based survey, which comprised five questions, has been available from the homepage of the web-version of the journal Diabetes Care throughout the month of December 2013, and on the AMD website between December 2013 and September 2014. Participation was totally free and responders were anonymous.

Results

Overall, 452 physicians (M=58.4%) participated in the survey. Diabetologists accounted for 76.8% of responders. The results of the survey show wide agreement (>90%) by participants on the utility of the algorithms proposed, even if they do not cover all possible needs of patients with T2DM for a personalized therapeutic approach. In the online survey period and in the months after its conclusion, a relevant and durable increase in the number of unique users who visited the websites was registered, compared to the period preceding the survey.

Conclusions

Patients with T2DM are heterogeneous, and there is interest toward accessible and easy to use personalized therapeutic algorithms. Responders opinions probably reflect the peculiar organization of diabetes care in each country.
Accuracy of musculoskeletal imaging for the diagnosis of polymyalgia rheumatica: systematic review
Authors: Mackie Sarah Louise , Koduri Gouri , Hill Catherine L , Wakefield Richard J , Hutchings Andrew , Loy Clement , Dasgupta Bhaskar , Wyatt Jeremy C
Published: August 2015

Objectives

To review the evidence for accuracy of imaging for diagnosis of polymyalgia rheumatica (PMR).

Methods

Searches included MEDLINE, EMBASE and PubMed. Evaluations of diagnostic accuracy of imaging tests for PMR were eligible, excluding reports with <10 PMR cases. Two authors independently extracted study data and three authors assessed methodological quality using modified QUADAS-2 criteria.

Results

26 studies of 2370 patients were evaluated: 10 ultrasound scanning studies; 6 MRI studies; 1 USS and MRI study; 7 18-fluorodeoxyglucose-positron emission tomography (PET) studies; 1 plain radiography and 1 technetium scintigraphy study. In four ultrasound studies, subacromial-subdeltoid bursitis had sensitivity 80% (95% CI 55% to 93%) and specificity 68% (95% CI 60% to 75%), whereas bilateral subacromial-subdeltoid bursitis had sensitivity 66% (95% CI 43% to 87%) and specificity 89% (95% CI 66% to 97%). Sensitivity for ultrasound detection of trochanteric bursitis ranged from 21% to 100%. In four ultrasound studies reporting both subacromial-subdeltoid bursitis and glenohumeral synovitis, detection of subacromial-subdeltoid bursitis was more accurate than that of glenohumeral synovitis (p=0.004). MRI and PET/CT revealed additional areas of inflammation in the spine and pelvis, including focal areas between the vertebrae and anterior to the hip joint, but the number of controls with inflammatory disease was inadequate for precise specificity estimates.

Conclusions

Subacromial-subdeltoid bursitis appears to be the most helpful ultrasound feature for PMR diagnosis, but interpretation is limited by study heterogeneity and methodological issues, including variability in blinding and potential bias due to case–control study designs. Recent MRI and PET/CT case–control studies, with blinded readers, yielded promising data requiring validation within a diagnostic cohort study.
Relationship between tissue stress during gait in healthy volunteers and patterns of urate deposition and bone erosion in gout: a biomechanical computational modelling study
Authors: Dalbeth Nicola , Deacon Michelle , Gamble Gregory D , Mithraratne Kumar , Fernandez Justin
Published: August 2015

Objectives

To determine whether patterns of high internal tissue stress during gait are associated with patterns of monosodium urate crystal deposition and bone erosion in gout.

Methods

We compared patterns of foot von Mises stress predicted computationally during gait in volunteers of normal and high body mass index (BMI) with patterns of urate deposition in gout and asymptomatic hyperuricaemia, and bone erosion in gout using dual-energy and conventional CT data.

Results

The highest average and peak von Mises stress during gait was observed at the third metatarsal (MT) head. Similar stress patterns were observed for high and low BMI groups. In contrast, for both urate deposition and bone erosion, the first MT head was most frequently affected, with very infrequent involvement of the third MT head. There was no clear relationship between average or peak von Mises stress patterns with patterns of urate deposition or bone erosion (−0.29>r<0.16). Addition of BMI into linear regression models did not alter the findings.

Conclusions

These data do not support the concept that elevated internal tissue stress during biomechanical loading plays an important role in patterns of monosodium urate crystal deposition or structural damage in gout.
Comparison of gabapentin versus topiramate on clinically affected dogs with Chiari‐like malformation and syringomyelia
Authors: Plessas I. N. , Volk H. A. , Rusbridge C. , Vanhaesebrouck A. E. , Jeffery N. D.
Published: August 2015

To date there is no evidence‐based data for efficacious treatment of neuropathic pain in dogs with Chiari‐like malformation (CM) and syringomyelia (SM). The objective of this prospective cross‐over study was to compare the effect of gabapentin versus topiramate, as an add‐on treatment to carprofen, on quality of life (QoL) of dogs experiencing signs of neuropathic pain due to CM/SM. A visual analogue scale (VAS) was used to assess the QoL: (1) on day 0; (2) after 1 week of carprofen only; (3) after 2 weeks on carprofen and gabapentin; and (4) after 2 weeks on carprofen and topiramate. No significant difference was observed between VAS after gabapentin or topiramate (P=0.91). However, an improvement in QoL was observed when gabapentin was compared with baseline (P=0.009), but not for topiramate. In conclusion, the addition of gabapentin was more effective in improving QoL than carprofen alone, but the study failed to identify that gabapentin was more efficacious than topiramate. Perhaps the more favourable side effect profile of the former makes it more suitable for the treatment of neuropathic pain associated with CM/SM but further placebo‐controlled trials are required to assess the efficacy of these drugs.
Is EBVM ethical?
Authors: Mills David
Published: August 2015

David Mills

has concerns about the extent to which the principles of evidence‐based medicine can be applied to individual veterinary practice.
Simulation of financial market via nonlinear Ising model
Authors: Ko Bonggyun , Song Jae Wook , Chang Woojin
Published: August 2015

In this research, we propose a practical method for simulating the financial return series whose distribution has a specific heaviness. We employ the Ising model for generating financial return series to be analogous to those of the real series. The similarity between real financial return series and simulated one is statistically verified based on their stylized facts including the power law behavior of tail distribution. We also suggest the scheme for setting the parameters in order to simulate the financial return series with specific tail behavior. The simulation method introduced in this paper is expected to be applied to the other financial products whose price return distribution is fat-tailed.
Applying Lipson's state models to marked graph diagrams of surface-links
Authors: Joung Yewon , Kamada Seiichi , Lee Sang Youl
Published: August 2015

A. S. Lipson constructed two state models yielding the same classical link invariant obtained from the Kauffman polynomial F(a, u). In this paper, we apply Lipson's state models to marked graph diagrams of surface-links, and observe when they induce surface-link invariants.
Side parameter for the torus with a single cone point
Authors: Akiyoshi Hirotaka
Published: August 2015

We introduce the side parameter map from the space of cone hyperbolic structures on the torus with a single cone point to the hyperbolic plane ℍ2, based on the idea in the Jorgensen theory for punctured torus Kleinian groups. Then, we show that the side parameter map is a homeomorphism.
Reidemeister moves and groups
Authors: Manturov Vassily Olegovich
Published: August 2015

Recently, the author discovered an interesting class of knot-like objects called free knots. These purely combinatorial objects are equivalence classes of Gauss diagrams modulo Reidemeister moves (the same notion in the language of words was introduced by Turaev [Topology of words, Proc. Lond. Math. Soc.95(3) (2007) 360–412], who thought all free knots to be trivial). As it turned out, these new objects are highly nontrivial, see [V. O. Manturov, Parity in knot theory, Mat. Sb.201(5) (2010) 65–110], and even admit nontrivial cobordism classes [V. O. Manturov, Parity and cobordisms of free knots, Mat. Sb.203(2) (2012) 45–76]. An important issue is the existence of invariants where a diagram evaluates to itself which makes such objects "similar" to free groups: An element has its minimal representative which "lives inside" any representative equivalent to it. In this paper, we consider generalizations of free knots by means of (finitely presented) groups. These new objects have lots of nontrivial properties coming from both knot theory and group theory. This connection allows one not only to apply group theory to various problems in knot theory but also to apply Reidemeister moves to the study of (finitely presented) groups. Groups appear naturally in this setting when graphs are embedded in surfaces.
Fuzzy Descriptor Models for Earthquake Time Prediction Using Seismic Time Series
Authors: Bahrami Behzad , Shafiee Masoud
Published: August 2015

In recent years, singular systems and fuzzy descriptor have attracted a lot of researchers' attention due to their wide practical applications for modeling complex phenomena. In this study, one approach proposed is the fuzzy clustering algorithm based on linear structures to identify the neuro Fuzzy local linear models. Additionally fuzzy descriptor models, a recently proposed neuro fuzzy interpretation of locally linear models, are implemented because of their promise for intuitive incremental learning algorithms e.g. Generalized Fuzzy Clustering Variety (GFCV). The results from the fuzzy descriptor models are compared to the results of several other methods. An efficient technique, based on the error indices of multiple validation sets, is used to optimize the number of neurons and prevent the algorithm from over fitting. The scope of this work is to reveal the advantages of fuzzy descriptor models and compare them to the most successful neural and neuro fuzzy approaches based on prediction accuracy, generalization, and computational complexity. The proposed solution is shown to accurately forecast seismic time series, outperforming several other methods.
Influence of Foundation Type on Seismic Performance of Buildings Considering Soil–Structure Interaction
Authors: Hokmabadi Aslan S. , Fatahi Behzad
Published: August 2015

In selecting the type of foundation best suited for mid-rise buildings in high risk seismic zones, design engineers may consider that a shallow foundation, a pile foundation, or a pile-raft foundation can best carry the static and dynamic loads. However, different types of foundations behave differently during earthquakes, depending on the soil–structure interaction (SSI) where the properties of the in situ soil and type of foundation change the dynamic characteristics (natural frequency and damping) of the soil–foundation–structure system. In order to investigate the different characteristics of SSI and its influence on the seismic response of building frames, a 3D numerical model of a 15-storey full-scale (prototype) structure was simulated with four different types of foundations: (i) A fixed-based structure that excludes the SSI, (ii) a structure supported by a shallow foundation, (iii) a structure supported by a pile-raft foundation in soft soil and (iv) a structure supported by a floating (frictional) pile foundation in soft soil. Finite difference analyzes with FLAC3D were then conducted using real earthquake records that incorporated material (soil and superstructure) and geometric (uplifting, gapping and [Formula: see text] effects) nonlinearities. The 3D numerical modeling procedure had previously been verified against experimental shaking table tests conducted by the authors. The results are then presented and compared in terms of soil amplification, shear force distribution and rocking of the superstructure, including its lateral deformation and drift. The results showed that the type of foundation is a major contributor to the seismic response of buildings with SSI and should therefore be given careful consideration in order to ensure a safe and cost effective design.
Robustness Testing of Model Based Multiple Criteria Decisions: Fundamentals and Applications
Authors: Wierzbicki Andrzej P. , Makowski Marek , Granat Janusz
Published: August 2015

Robustness or insensitivity is a desirable property of decisions; however, most texts on robustness and/or sensitivity analysis do not define it precisely. A broad literature in this field concentrates on robust design of decisions (including robust optimization). This paper focuses on robustness testing, that is, checking whether a design has actually resulted in robust properties of the system if some of basic assumptions are changed. We propose a general framework of such robustness testing and show that robustness is a property of the relation between three (classes of) models: a basic model of the decision situation, a second model of possible perturbations of the first model, and a model of implementation of the decision, optionally taking into account some measurements of the impact of perturbations. Typical approaches to robustness or sensitivity analysis assume tacitly that the first two models can be combined and analyze parameters deviations in one combined model. However, the role of the first two models can be asymmetric if some optimization of the decision is performed on the first model. We extend this framework, intended originally for single criteria (scalar) optimization to multiple criteria (vector) optimization. The proposed approach is illustrated by diverse examples.
Water-soluble porphyrin-phosphonate conjugates as potential photodynamic therapy photosensitizers
Authors: Lu Yunguo , Chen Zhihang , Yu Bingqiong , Yan Kun , Li Zaoying
Published: August 2015

Two novel water-soluble porphyrin-phosphonate conjugates were synthesized and characterized. Although both conjugates showed significant potential in photodynamic therapy, the variety of their structure induced the obvious differences in the binding manner with calf thymus DNA, the cytotoxicity and the cellular sublocalization.
Preparation and Characterization of Fe3O4@nSiO2@mSiO2–NH2 Core–Shell Microspheres for Extracting Allura Red from Aqueous Solution
Authors: Xi Desheng , Deng Xiaojuan , Li Huijun , Yao Pei
Published: August 2015

Allura red (AR) is a water-soluble synthetic colorant often used as an additive in the food industry, but excess AR can be harmful to human health. In this work, we report the development of a new removal method for AR by using amino-functionalized microspheres with Fe3O4 cores and twolayer shells composed of SiO2 particles and perpendicularly aligned mesoporous SiO2 (designated Fe3O4@nSiO2@mSiO2–NH2). The material exhibits good dispersibility in aqueous solutions and a high saturation magnetization of 45.68[Formula: see text]emu[Formula: see text]g[Formula: see text], and can be magnetically separated efficiently with an external magnet. Importantly, the material has great adsorption capacity of 29.6[Formula: see text]mg[Formula: see text]g[Formula: see text] for AR and the capacity for reuse with a simple treatment. The adsorption process is very fast and the kinetics data are consistent with a pseudo-second order model. Based on these, a rapid and efficient method for extraction and analysis of AR in water and soft drinks has been established.
Solution Aging Effects on the Performance and Morphology of P3HT: PCBM Bulk Heterojunction Solar Cells
Authors: Yu Fei , Kuppa Vikram K.
Published: August 2015

In a bulk heterojunction photovoltaic device, the morphology of the active layer strongly affects the device performance. By comparing the device performance from P3HT:PCBM solutions that were aged for different times, we notice that aging time has an influence on device power conversion efficiency. We prove the morphological difference in P3HT:PCBM thin films is caused by different aging time, and demonstrate a relationship between the P3HT:PCBM phase behavior and BHJ device performance through UV-Vis absorption spectrum and atomic force microscope.
Irrigator and Environmental Water Management Adaptation to Climate Change and Water Reallocation in the Murray–Darling Basin
Authors: Kirby Mac , Connor Jeff , Ahmad Mobin-ud Din , Gao Lei , Mainuddin Mohammed
Published: August 2015

In an earlier paper (Kirby et al. 2014a), we showed that climate change and a new policy which reallocates water to the environment will impact both the flow of water and the income derived from irrigation in the Murray–Darling Basin. Here, we extend the analysis to consider irrigator and environmental water management strategies to adapt to these new circumstances. Using an integrated hydrology-economics model, we examine a range of strategies and their impact on flows and the gross income of irrigation.

We show that the adaptation strategies provide a range of flow and economic outcomes in the Basin. Several strategies offer significant scope to enhance flows without large adverse impacts on the gross income of irrigation overall. Some environmental water management strategies enhance flows in the Murray part of the basin even under the drying influence of a projected median climate change. Irrigator strategies that include carryover of water in storage from one year to the next provide for lesser year to year variability in gross income and may be regarded as more advantageous in providing security against droughts. Flows and the gross income of low value irrigation industries strategies are sensitive to climate change, irrespective of adaptation strategy. Should a projected dry extreme climate change be realized, no strategy can prevent a large reduction in flows and also in gross income, particularly of low value irrigation industries. Nevertheless, environmental water management strategies mitigate the impact on flows, and in some cases may also help mitigate the impacts on gross income. High value irrigation industries are less affected (in terms of gross income, though net income will reduce because of rising water prices) by projected climate change, consistent with observation in the recent long term drought.
Chronotopes, Scales, and Complexity in the Study of Language in Society
Authors: Blommaert Jan
Published: August 2015

Recent developments in the study of language in society have moved the field increasingly away from linear models toward complex models. The complexity of timespace as an aspect of what is called context is of key importance in this development, and this article engages with two possibly useful concepts in view of this: chronotope and scale. Chronotope can be seen as invokable chunks of history that organize the indexical order of discourse; scale, in turn, can be seen as the scope of communicability of such invocations. Thus, whenever we see chronotopes, we see them mediated by scales. The cultural stuff of chronotopes is conditioned by the sociolinguistic conditions of scale. This nuanced approach to timescale contextualization offers new directions for complexity-oriented research in our fields.
Nuclear Forces and Their Impact on Neutron-Rich Nuclei and Neutron-Rich Matter
Authors: Hebeler K. , Holt J.D. , Menéndez J. , Schwenk A.
Published: August 2015

We review the impact of nuclear forces on matter at neutron-rich extremes. Recent results have shown that neutron-rich nuclei become increasingly sensitive to three-nucleon forces, which are at the forefront of theoretical developments based on effective field theories of quantum chromodynamics. These developments include the formation of shell structure, the spectroscopy of exotic nuclei, and the location of the neutron drip line. Nuclear forces also constrain the properties of neutron-rich matter, including the neutron skin, the symmetry energy, and the structure of neutron stars. First, we review our understanding of three-nucleon forces and show how chiral effective field theory makes unique predictions for many-body forces. Then, we survey results with three-nucleon forces in neutron-rich oxygen and calcium isotopes and neutron-rich matter, which have been explored with a range of many-body methods. Three-nucleon forces therefore provide an exciting link between theoretical, experimental, and observational nuclear physics frontiers.
O-GlcNAcase overexpression reverses coronary endothelial cell dysfunction in type 1 diabetic mice
Authors: Makino Ayako , Dai Anzhi , Han Ying , Youssef Katia D. , Wang Weihua , Donthamsetty Reshma , Scott Brian T. , Wang Hong , Dillmann Wolfgang H.
Published: August 2015

Cardiovascular disease is the primary cause of morbidity and mortality in diabetes, and endothelial dysfunction is commonly seen in these patients. Increased O-linked N-acetylglucosamine ( O-GlcNAc) protein modification is one of the central pathogenic features of diabetes. Modification of proteins by O-GlcNAc ( O-GlcNAcylation) is regulated by two key enzymes: β- N-acetylglucosaminidase [ O-GlcNAcase (OGA)], which catalyzes the reduction of protein O-GlcNAcylation, and O-GlcNAc transferase (OGT), which induces O-GlcNAcylation. However, it is not known whether reducing O-GlcNAcylation can improve endothelial dysfunction in diabetes. To examine the effect of endothelium-specific OGA overexpression on protein O-GlcNAcylation and coronary endothelial function in diabetic mice, we generated tetracycline-inducible, endothelium-specific OGA transgenic mice, and induced OGA by doxycycline administration in streptozotocin-induced type 1 diabetic mice. OGA protein expression was significantly decreased in mouse coronary endothelial cells (MCECs) isolated from diabetic mice compared with control MCECs, whereas OGT protein level was markedly increased. The level of protein O-GlcNAcylation was increased in diabetic compared with control mice, and OGA overexpression significantly decreased the level of protein O-GlcNAcylation in MCECs from diabetic mice. Capillary density in the left ventricle and endothelium-dependent relaxation in coronary arteries were significantly decreased in diabetes, while OGA overexpression increased capillary density to the control level and restored endothelium-dependent relaxation without changing endothelium-independent relaxation. We found that connexin 40 could be the potential target of O-GlcNAcylation that regulates the endothelial functions in diabetes. These data suggest that OGA overexpression in endothelial cells improves endothelial function and may have a beneficial effect on coronary vascular complications in diabetes.
Autonomous requirements of the Menkes disease protein in the nervous system
Authors: Hodgkinson Victoria L. , Zhu Sha , Wang Yanfang , Ladomersky Erik , Nickelson Karen , Weisman Gary A. , Lee Jaekwon , Gitlin Jonathan D. , Petris Michael J.
Published: August 2015

Menkes disease is a fatal neurodegenerative disorder arising from a systemic copper deficiency caused by loss-of-function mutations in a ubiquitously expressed copper transporter, ATP7A. Although this disorder reveals an essential role for copper in the developing human nervous system, the role of ATP7A in the pathogenesis of signs and symptoms in affected patients, including severe mental retardation, ataxia, and excitotoxic seizures, remains unknown. To directly examine the role of ATP7A within the central nervous system, we generated Atp7a Nes mice, in which the Atp7a gene was specifically deleted within neural and glial cell precursors without impairing systemic copper homeostasis, and compared these mice with the mottled brindle ( mo-br) mutant, a murine model of Menkes disease in which Atp7a is defective in all cells. Whereas mo-br mice displayed neurodegeneration, demyelination, and 100% mortality prior to weaning, the Atp7a Nes mice showed none of these phenotypes, exhibiting only mild sensorimotor deficits, increased anxiety, and susceptibility to NMDA-induced seizure. Our results indicate that the pathophysiology of severe neurological signs and symptoms in Menkes disease is the result of copper deficiency within the central nervous system secondary to impaired systemic copper homeostasis and does not arise from an intrinsic lack of ATP7A within the developing brain. Furthermore, the sensorimotor deficits, hypophagia, anxiety, and sensitivity to NMDA-induced seizure in the Atp7a Nes mice reveal unique autonomous requirements for ATP7A in the nervous system. Taken together, these data reveal essential roles for copper acquisition in the central nervous system in early development and suggest novel therapeutic approaches in affected patients.
Ball Milling to Build the Hybrid Mesocrystals of Ibuprofen and Aragonite
Authors: Cho Kyoung A , Choi Insil , Kim Il Won
Published: August 2015

Mesocrystal formation is one of the new paradigms of the nonclassical crystallization, where the assembly of crystal domains is observed. Also, it has been recently employed in studies on drug formulation to utilize controlled dissolution of the drug domains. In this report, ibuprofen was attempted to form hybrid mesocrystals with calcium carbonate crystals. Two polymorphs of calcium carbonate (aragonite and calcite) were used during the solid‐state process of ball milling. Structural analyses confirmed the mesocrystal formation of ibuprofen with aragonite but not with calcite. The origin of the observed behavior was found from the higher affinity of ibuprofen to aragonite, especially its (0 1 0) surface, compared to calcite. The hybrid mesocrystals of ibuprofen and aragonite showed the environment‐responsive release behavior, where the stability of aragonite was the controlling factor for the release kinetics of ibuprofen.
Impact of NiOx Buffer Layers on the Dielectric Properties of BaTiO3 Thin Films on Nickel Substrates Fabricated by Polymer Assisted Deposition
Authors: Du Hui , Li Yang , Liang Wei Zheng , Wang Yu Xuan , Gao Min , Huang Wen , Zhang Yin , Lin Yuan
Published: August 2015

Structural health monitoring with piezoelectric thin films integrated on structural metals shows great advantages for potential applications. However, the integration of piezoelectric thin films on structure metals is still challenged. In this paper, we report the piezoelectric barium titanate [BaTiO3 (BTO)] thin films deposited on polycrystalline Ni substrates by the polymer assisted deposition (PAD) method using NiOx as the buffer layers. The NiOx buffer layers with different thicknesses were prepared by varying immersing time from 5 minutes to 4 hours in H2O2 solution. The dielectric and leakage current properties of the thin films have been studied by general test systems. The BTO/Ni heterostructure with 2‐hour immersing time exhibits better dielectric properties with a dielectric constant over 1500 and a 34.8% decrease of the dielectric loss compared to that with 5‐minute immersing time. The results show that the leakage current density is strongly affected by the thickness of the NiOx buffer layer. The conduction mechanisms of the BTO/Ni heterostructure have been discussed according to the J‐V characteristic curves.
Acute Respiratory Distress Syndrome after Treatment of Metastatic Prostate Cancer with Taxotere: A Case Report and Literature Review
Authors: Raufi Ali , Dotson Jennifer , Khasawneh Mohamad
Published: August 2015

Prostate cancer is the most common cancer in men. Docetaxel is a common chemotherapeutic agent that has proven its efficacy in the treatment of patients with both castration sensitive and resistant metastatic prostate cancer. We report a case of acute respiratory distress syndrome (ARDS) in a patient with metastatic prostate cancer treated with docetaxel (Taxotere). ARDS is very rare but life threatening complication of docetaxel which requires aggressive supportive care and close monitoring. Better awareness and prompt diagnosis of this treatment related ARDS will improve the effectiveness and outcome of its management.
Some Relations between Admissible Monomials for the Polynomial Algebra
Authors: Mothebe Mbakiso Fix , Uys Lafras
Published: August 2015

LetP(n)=F2[x1,…,xn]be the polynomial algebra innvariablesxi, of degree one, over the fieldF2of two elements. The mod-2 Steenrod algebraAacts onP(n)according to well known rules. A major problem in algebraic topology is of determiningA+P(n), the image of the action of the positively graded part ofA. We are interested in the related problem of determining a basis for the quotient vector spaceQ(n)=P(n)/A+P(n).Q(n)has been explicitly calculated forn=1,2,3,4but problems remain forn≥5. BothP(n)=⨁d≥0Pd(n)andQ(n)are graded, wherePd(n)denotes the set of homogeneous polynomials of degreed. In this paper, we show that ifu=x1m1⋯xn-1mn-1∈Pd′(n-1)is an admissible monomial (i.e.,umeets a criterion to be in a certain basis forQ(n-1)), then, for any pair of integers (j,λ),1≤j≤n, andλ≥0, the monomialhjλu=x1m1⋯xj-1mj-1xj2λ-1xj+1mj⋯xnmn-1∈Pd′+(2λ-1)(n)is admissible. As an application we consider a few cases whenn=5.
CTLL: A Cell-Based Transfer Learning Method for Localization in Large Scale Wireless Sensor Networks
Authors: Tang Zhanyong , Zhang Jie , Gong Xiaoqing , Cheng Xiaohua , Chen Xiaojiang , Fang Dingyi , Wang Wei
Published: August 2015

Localization is emerging as a fundamental component in wireless sensor network and is widely used in the field of environmental monitoring, national and military defense, transportation monitoring, and so on. Current localization methods, however, focus on how to improve accuracy without considering the robustness. Thus, the error will increase rapidly when nodes density and SNR (signal to noise ratio) have changed dramatically. This paper introduces CTLL, Cell-Based Transfer Learning Method for Localization in WSNs, a new way for localization which is robust to the variances of nodes density and SNR. The method combines samples transfer learning and SVR (Support Vector Regression) regression model to get a better performance of localization. Unlike past work, which considers that the nodes density and SNR are invariable, our design applies regional division and transfer learning to adapt to the variances of nodes density and SNR. We evaluate the performance of our method both on simulation and realistic deployment. The results show that our method increases accuracy and provides high robustness under a low cost.
The Gelation Ability and Morphology Study of Organogel System Based on Calamitic Hydrazide Derivatives
Authors: Ran Xia , Shi Lili , Zhang Kun , Lou Jie , Liu Bo , Guo Lijun
Published: August 2015

The gelation property of a series of LMOG bearing hydrazide and azobenzene groups, namely, N‐4‐(alkoxyphenyl)‐N′‐4‐[(4‐methoxyphenyl)azophenyl] benzohydrazide (BNBC‐n, n = 8,12,14), has been systematically studied in this work. The obtained results demonstrate that the gelling ability in organic solvents is significantly influenced by the length of terminal alkoxy chain. In different organic solvents, it is hard to observe the organogel formation for BNBC‐8 molecule. On the contrary, the organogelators BNBC‐12 and BNBC‐14 bearing longer terminal chains have shown great ability to gel organic solvents to form stable organogels. The critical gelation concentration for BNBC‐12 reaches as low as 5.3 × 10−3 M, which can be considered as a supergelator. It has been manifested that the aggregation morphology of organogel strongly depends on the nature of the gelling solvents and the length of the terminal alkoxy chain. The gelation of BNBC‐n provides an easy method for the preparation of multidimensional structure and manipulation of morphology from ribbons, hollow tube fiber to 3D net‐like structure in different solvents. The cooperation of hydrogen bonding, π‐π interaction, and Van der Waals force is suggested to be the main contribution to this self‐assembled structure.