bluuebunny/crossref_metadata_2025 huggingface dataset:
Changes in Susceptibility to Oncolytic Vesicular Stomatitis Virus during Progression of Prostate Cancer
Authors: Yu Nanmeng , Puckett Shelby , Antinozzi Peter A. , Cramer Scott D. , Lyles Douglas S.
Published: March 2015

A major challenge to oncolytic virus therapy is that individual cancers vary in their sensitivity to oncolytic viruses, even when these cancers arise from the same tissue type. Variability in response may arise due to differences in the initial genetic lesions leading to cancer development. Alternatively, susceptibility to viral oncolysis may change during cancer progression. These hypotheses were tested using cells from a transgenic mouse model of prostate cancer infected with vesicular stomatitis virus (VSV). Primary cultures from murine cancers derived from prostate-specific
Pten
deletion contained a mixture of cells that were susceptible and resistant to VSV. Castration-resistant cancers contained a higher percentage of susceptible cells than cancers from noncastrated mice. These results indicate both susceptible and resistant cells can evolve within the same tumor. The role of
Pten
deletion was further investigated using clonal populations of murine prostate epithelial (MPE) progenitor cells and tumor-derived
Pten
−/−
cells. Deletion of
Pten
in MPE progenitor cells using a lentivirus vector resulted in cells that responded poorly to interferon and were susceptible to VSV infection. In contrast, tumor-derived
Pten
−/−
cells expressed higher levels of the antiviral transcription factor STAT1, activated STAT1 in response to VSV, and were resistant to VSV infection. These results suggest that early in tumor development following
Pten
deletion, cells are primarily sensitive to VSV, but subsequent evolution in tumors leads to development of cells that are resistant to VSV infection. Further evolution in castration-resistant tumors leads to tumors in which cells are primarily sensitive to VSV.

IMPORTANCE
There has been a great deal of progress in the development of replication-competent viruses that kill cancer cells (oncolytic viruses). However, a major problem is that individual cancers vary in their sensitivity to oncolytic viruses, even when these cancers arise from the same tissue type. The experiments presented here were to determine whether both sensitive and resistant cells are present in prostate cancers originating from a single genetic lesion in transgenic mice, prostate-specific deletion of the gene for the tumor suppressor Pten. The results indicate that murine prostate cancers are composed of both cells that are sensitive and cells that are resistant to oncolytic vesicular stomatitis virus (VSV). Furthermore, androgen deprivation led to castration-resistant prostate cancers that were composed primarily of cells that were sensitive to VSV. These results are encouraging for the use of VSV for the treatment of prostate cancers that are resistant to androgen deprivation therapy.
Exosomal Communication Goes Viral
Authors: Meckes David G.
Published: March 2015

Exosomes are small vesicles secreted from cells that participate in intercellular communication events. Accumulating evidence demonstrates that host exosome pathways are hijacked by viruses and that virally modified exosomes contribute to virus spread and immune evasion. In the case of tumor viruses, recent findings suggest that alterations in normal exosome biology may promote the development and progression of cancer. These studies will be discussed in the context of our current knowledge of Epstein-Barr virus (EBV)-modified exosomes.
Neuraminidase Mutations Conferring Resistance to Oseltamivir in Influenza A(H7N9) Viruses
Authors: Marjuki Henju , Mishin Vasiliy P. , Chesnokov Anton P. , De La Cruz Juan A. , Davis Charles T. , Villanueva Julie M. , Fry Alicia M. , Gubareva Larisa V.
Published: March 2015

Human infections by avian influenza A(H7N9) virus entail substantial morbidity and mortality. Treatment of infected patients with the neuraminidase (NA) inhibitor oseltamivir was associated with emergence of viruses carrying NA substitutions. In the NA inhibition (NI) assay, R292K conferred highly reduced inhibition by oseltamivir, while E119V and I222K each caused reduced inhibition. To facilitate establishment of laboratory correlates of clinically relevant resistance, experiments were conducted in ferrets infected with virus carrying wild-type or variant NA genes recovered from the A/Taiwan/1/2013 isolate. Oseltamivir treatment (5 or 25 mg/kg of body weight/dose) was given 4 h postinfection, followed by twice-daily treatment for 5 days. Treatment of ferrets infected with wild-type virus resulted in a modest dose-dependent reduction (0.7 to 1.5 log1050% tissue culture infectious dose [TCID50]) in nasal wash viral titers and inflammation response. Conversely, treatment failed to significantly inhibit the replication of R292K or E119V virus. A small reduction of viral titers was detected on day 5 in ferrets infected with the I222K virus. The propensity for oseltamivir resistance emergence was assessed in oseltamivir-treated animals infected with wild-type virus; emergence of R292K virus was detected in 3 of 6 ferrets within 5 to 7 days postinfection. Collectively, we demonstrate that R292K, E119V, and I222K reduced the inhibitory activity of oseltamivir, not only in the NI assay, but also in infected ferrets, judged particularly by viral loads in nasal washes, and may signal the need for alternative therapeutics. Thus, these clinical outcomes measured in the ferret model may correlate with clinically relevant oseltamivir resistance in humans.

IMPORTANCEThis report provides more evidence for using the ferret model to assess the susceptibility of influenza A(H7N9) viruses to oseltamivir, the most prescribed anti-influenza virus drug. The information gained can be used to assist in the establishment of laboratory correlates of human disease and drug therapy. The rapid emergence of viruses with R292K in treated ferrets correlates well with the multiple reports on this NA variant in treated human patients. Our findings highlight the importance of the discovery and characterization of new antiviral drugs with different mechanisms of action and the use of combination treatment strategies against emerging viruses with pandemic potential, such as avian H7N9 virus, particularly against those carrying drug resistance markers.
Peptide-Dependent Recognition of HLA-B*57:01 by KIR3DS1
Authors: O'Connor Geraldine M. , Vivian Julian P. , Gostick Emma , Pymm Phillip , Lafont Bernard A. P. , Price David A. , Rossjohn Jamie , Brooks Andrew G. , McVicar Daniel W.
Published: March 2015

Killer cell immunoglobulin-like receptors (KIRs) play an important role in the activation of natural killer (NK) cells, which in turn contribute to the effective immune control of many viral infections. In the context of HIV infection, the closely related KIR3DL1 and KIR3DS1 molecules, in particular, have been associated with disease outcome. Inhibitory signals via KIR3DL1 are disrupted by downregulation of HLA class I ligands on the infected cell surface and can also be impacted by changes in the presented peptide repertoire. In contrast, the activatory ligands for KIR3DS1 remain obscure. We used a structure-driven approach to define the characteristics of HLA class I-restricted peptides that interact with KIR3DL1 and KIR3DS1. In the case of HLA-B*57:01, we used this knowledge to identify bona fide HIV-derived peptide epitopes with similar properties. Two such peptides facilitated productive interactions between HLA-B*57:01 and KIR3DS1. These data reveal the presence of KIR3DS1 ligands within the HIV-specific peptide repertoire presented by a protective HLA class I allotype, thereby enhancing our mechanistic understanding of the processes that enable NK cells to impact disease outcome.

IMPORTANCENatural killer (NK) cells are implicated as determinants of immune control in many viral infections, but the precise molecular mechanisms that initiate and control these responses are unclear. The activating receptor KIR3DS1 in combination with HLA-Bw4 has been associated with better outcomes in HIV infection. However, evidence of a direct interaction between these molecules is lacking. In this study, we demonstrate that KIR3DS1 recognition of HLA-Bw4 is peptide dependent. We also identify HIV-derived peptide epitopes presented by the protective HLA-B*57:01 allotype that facilitate productive interactions with KIR3DS1. Collectively, these findings suggest a mechanism whereby changes in the peptide repertoire associated with viral infection provide a trigger for KIR3DS1 engagement and NK cell activation.
Functional Properties and Genetic Relatedness of the Fusion and Hemagglutinin-Neuraminidase Proteins of a Mumps Virus-Like Bat Virus
Authors: Krüger Nadine , Hoffmann Markus , Drexler Jan Felix , Müller Marcel Alexander , Corman Victor Max , Sauder Christian , Rubin Steven , He Biao , Örvell Claes , Drosten Christian , Herrler Georg
Published: March 2015

A bat virus with high phylogenetic relatedness to human mumps virus (MuV) was identified recently at the nucleic acid level. We analyzed the functional activities of the hemagglutinin-neuraminidase (HN) and the fusion (F) proteins of the bat virus (batMuV) and compared them to the respective proteins of a human isolate. Transfected cells expressing the F and HN proteins of batMuV were recognized by antibodies directed against these proteins of human MuV, indicating that both viruses are serologically related. Fusion, hemadsorption, and neuraminidase activities were demonstrated for batMuV, and either bat-derived protein could substitute for its human MuV counterpart in inducing syncytium formation when coexpressed in different mammalian cell lines, including chiropteran cells. Cells expressing batMuV glycoproteins were shown to have lower neuraminidase activity. The syncytia were smaller, and they were present in lower numbers than those observed after coexpression of the corresponding glycoproteins of a clinical isolate of MuV (hMuV). The phenotypic differences in the neuraminidase and fusion activity between the glycoproteins of batMuV and hMuV are explained by differences in the expression level of the HN and F proteins of the two viruses. In the case of the F protein, analysis of chimeric proteins revealed that the signal peptide of the bat MuV fusion protein is responsible for the lower surface expression. These results indicate that the surface glycoproteins of batMuV are serologically and functionally related to those of hMuV, raising the possibility of bats as a reservoir for interspecies transmission.

IMPORTANCEThe recently described MuV-like bat virus is unique among other recently identified human-like bat-associated viruses because of its high sequence homology (approximately 90% in most genes) to its human counterpart. Although it is not known if humans can be infected by batMuV, the antigenic relatedness between the bat and human forms of the virus suggests that humans carrying neutralizing antibodies against MuV are protected from infection by batMuV. The close functional relationship between MuV and batMuV is demonstrated by cooperation of the respective HN and F proteins to induce syncytium formation in heterologous expression studies. An interesting feature of the glycoproteins of batMuV is the downregulation of the fusion activity by the signal peptide of F, which has not been reported for other paramyxoviruses. These results are important contributions for risk assessment and for a better understanding of the replication strategy of batMuV.
Takotsubo cardiomyopathy case series: typical, atypical and recurrence
Authors: Lagan Jakub , Connor Victoria , Saravanan Palaniappan
Published: March 2015

Takotsubo cardiomyopathy (TCM) is characterised by a transient left ventricular (LV) dysfunction, ECG changes that can imitate acute myocardial infarction and positive cardiac biomarkers in the absence of obstructive coronary artery disease. The exact pathogenesis of TCM is unclear but emotional or physical stress is a common denominator. We present three cases encompassing a spectrum of the disease: A typical TCM with apical LV dyskinesis, an atypical TCM with mid-ventricular regions affected and a TCM recurrence. Our cases show that TCM symptoms vary between individuals and may vary in the same patient. All our patients reported acute emotional stress prior to the onset of symptoms, had LV systolic dysfunction, positive cardiac biomarkers and non-obstructed coronary arteries. In all cases, LV systolic dysfunction eventually improved. TCM may account for 0.7–2.5% of acute coronary syndromes. It is more prevalent in the female population and can reoccur. Treatment is mainly supportive.
A population-based observational study on the factors associated with the completion of palliative chemotherapy among patients with oesophagogastric cancer
Authors: Groene Oliver , Crosby Tom , Hardwick Richard Henry , Riley Stuart , Greenaway Kimberley , Cromwell David
Published: March 2015

Objectives

Palliative chemotherapy is routinely given to patients diagnosed with locally advanced or metastatic oesophagogastric (O-G) cancer. We examine which patients with O-G cancer in England receive palliative chemotherapy, and identify factors associated with treatment completion.

Design

A prospective population-based observational study.

Setting

All English National Health Service (NHS) trusts diagnosing patients with O-G cancer.

Participants

Data were prospectively collected on patients diagnosed with invasive epithelial cancer of the oesophagus or stomach between 1 October 2007 and 30 June 2009 in English NHS hospitals, and those who had palliative treatment intent.

Outcome measure

We calculated the proportion of patients with different characteristics (eg, age, sex, stage at diagnosis, performance status) starting palliative chemotherapy. Multiple logistic regression was used to identify characteristics associated with non-completion of chemotherapy.

Results

There were 9768 patients in the study whose treatment intent was palliative. Among these, 2313 (24%) received palliative chemotherapy. It was received by 51% of patients aged under 55 years but only 9% of patients aged 75 years or over. Overall, 917 patients (53%) completed their treatment among the 1741 patients for whom information on treatment completion was recorded. Treatment completion ranged from 50–60% for patients with good performance status but was under 35% for patients aged 55 years or older with poor performance status. Treatment completion was not associated with site of cancer, pretreatment stage, sex, comorbidities or histology.

Conclusions

Completion rates of palliative chemotherapy in patients with O-G cancer are low and elderly patients with poor performance status are very unlikely to complete a palliative chemotherapy treatment. Clinicians and patients should consider this information when balancing potential (survival) benefits, toxicity of treatment and its effect on quality of life.
Symmetry breaking in the axial symmetrical configurations of enolic propanedial, propanedithial, and propanediselenal: pseudo Jahn–Teller effect versus the resonance-assisted hydrogen bond theory
Authors: Jalali Elahe , Nori-Shargh Davood
Published: March 2015

The origin of the symmetry breaking in the axial symmetrical configurations of enolic propanedial (1), propanedithial (2), and propanediselenal (3) have been investigated by means of time-dependence density functional theory and natural bond orbital interpretations. The results obtained at the quantum chemistry composite (G2MP2, CBS-QB3), ab initio molecular orbital (MP2/6-311++G**), and hybrid density functional theory (B3LYP/6-311++G**) levels of theory showed that the hydrogen-centered synchronous axial symmetrical (C2v) configurations of compounds 1–3 possessing the maximum π-electron delocalization within the M1=C2–C3=C4–M5–H6 keto-enol groups are less stable than their corresponding plane symmetrical (Cs) forms. Importantly, the symmetry breaking in the C2v configurations of the enol forms of compounds 1–3 to their corresponding plane symmetrical Cs configurations is due to the pseudo Jahn–Teller effect (PJTE) by mixing the ground A1 and excited B2 electronic states resulting in a PJT (A1 + B2) ⊗ b2 problem. We may expect that by the decrease of the energy gaps between reference states in the C2v forms that are involved in the PJTE decrease from compound 1 to compound 3, the PJT stabilization energy (PJTSE) may increase but the results obtained showed that the corresponding PJTSEs decrease. This fact can be justified by the increase of the electron delocalizations from the nonbonding orbitals of the C=M moieties to the antibonding orbitals of the H–M bonds, which leads to an increase of the π-electron delocalization within the M1=C2–C3=C4–M5–H6 keto-enol groups. In confrontation between the impacts of the resonance-assisted hydrogen bond and PJTE in the structural and configurational properties of compounds 1–3, PJTE has an overwhelming contribution and causes the symmetry breaking of the C2v configurations to their corresponding Cs forms. The correlations between the structural parameters, synchronicity indices, natural charges, PJTSEs, electron delocalizations, and the hardness of compounds 1–3 have been investigated.
Natural regeneration determines wintering bird presence in wind-damaged coniferous forest stands independent of postdisturbance logging
Authors: Werner Sinja A.B. , Müller Jörg , Heurich Marco , Thorn Simon
Published: March 2015

Natural disturbances in European production forests are undesired from an economic perspective but are important drivers of biodiversity. The removal of damaged timber to restore economic value is accompanied by negative effects on various species groups, particularly breeding bird communities, and can hinder natural regeneration. However, little is known about the effect of postdisturbance logging on bird assemblages in winter when temperatures are low and food resources are unpredictable. We conducted fixed-radius point counts of wintering birds in forest stands logged or unlogged after windthrows and in mature forest stands to test our predictions that bird species densities and abundances (i) are lower in postdisturbance logged stands and (ii) depend on the amount of natural regeneration, (iii) which differs between logged and unlogged stands. Our generalized linear mixed model did not support the expected differences in bird abundance or species densities between postdisturbance logged and unlogged stands but indicated that mature forest stands harbor the highest bird abundances and species densities. The number of regenerated coniferous trees significantly positively affected wintering bird abundances in both postdisturbance logged and unlogged stands. Hence, the number of coniferous trees appears to be a main predictor of wintering bird presence.
Numerical study of unsteady MHD oblique stagnation point flow with heat transfer over an oscillating flat plate
Authors: Javed Tariq , Ghaffari Abuzar , Ahmad Hussain
Published: March 2015

Unsteady stagnation point flow impinging obliquely on an oscillating flat plate in the presence of a uniform applied magnetic field in a fixed frame has been studied. The governing boundary layer equations are transformed into three coupled, dimensionless, nonlinear, partial differential equations. Here the stream function is expressed as Hiemenz and tangential components. The equations are solved numerically by using the well-known implicit finite difference scheme, called the Keller-box method. To ensure the accuracy of obtained results, numerical results are compared with the results available in the literature. It is observed that the obtained solution is in excellent agreement with previous studies. The effects of pertinent parameters involved in the problem, namely, magnetic parameter, Prandtl number, and impinging angle, on flow and heat transfer characteristics are illustrated. It is observed that the magnetic field helps to translate the oblique stagnation point.
On composite types of tunnel number two knots
Authors: Morimoto Kanji
Published: March 2015

Let K be a tunnel number two knot. Then, by considering the (g, b)-decompositions, K is one of (3, 0), (2, 1), (1, 2) or (0, 3)-knots. In this paper, we analyze the connected sum summands of composite tunnel number two knots and give a complete table of those summands from the point of view of (g, b)-decompositions.
Change Propagation and Conflict Resolution for the Co-Evolution of Business Processes
Authors: Grossmann Georg , Mafazi Shamila , Mayer Wolfgang , Schrefl Michael , Stumptner Markus
Published: March 2015

In large organizations, multiple stakeholders may modify the same business process. This paper addresses the problem when stakeholders perform changes on process views which become inconsistent with the business process and other views. Related work addressing this problem is based on execution trace analysis which is performed in a post-analysis phase and can be complex when dealing with large business process models. In this paper, we propose a design-based approach that can efficiently check consistency criteria and propagate changes on-the-fly from a process view to its reference process and related process views. The technique is based on consistent specialization of business processes and supports the control flow aspect of processes. Consistency checks can be performed during the design time by checking simple rules which support an efficient change propagation between views and reference process.
Stable intersection of middle-α Cantor sets
Authors: Pourbarat M.
Published: March 2015

We introduce a pair of middle Cantor sets which have stable intersection, while the product of their thickness is smaller than one.
On semi-rational Frobenius groups
Authors: Alavi Seyed Hassan , Daneshkhah Ashraf , Darafsheh Mohammad Reza
Published: March 2015

An element of a group G is called semi-rational if there is a natural number m such that each generator of 〈x〉 belongs to the conjugacy class of G containing x or xm. If all elements of G are semi-rational, then G is called a semi-rational group. In this paper, we study semi-rational Frobenius groups G and obtain results concerning effect of semi-rationality property on the kernel and complement of G. In particular, we show that ∣π(G)∣ ≤ 5 which answers Problem 2 in [D. Chillag and S. Dolfi, Semi-rational solvable groups, J. Group Theory13(4) (2010) 535–548] for semi-rational Frobenius groups.
Klein's programme and quantum mechanics
Authors: Clemente-Gallardo Jesús , Marmo Giuseppe
Published: March 2015

We review the geometrical formulation of quantum mechanics to identify, according to Klein's programme, the corresponding group of transformations. For closed systems, it is the unitary group. For open quantum systems, the semigroup of Kraus maps contains, as a maximal subgroup, the general linear group. The same group emerges as the exponentiation of the C*-algebra associated with the quantum system, when thought of as a Lie algebra. Thus, open quantum systems seem to identify the general linear group as associated with quantum mechanics and moreover suggest to extend the Klein programme also to groupoids. The usual unitary group emerges as a maximal compact subgroup of the general linear group.
Dynamics behaviors of a delayed competitive system in a random environment
Authors: Tan Ronghua , Xiang Huili , Chen Yiping , Liu Zhijun
Published: March 2015

In the real world, the population systems are often subject to white noises and a system with such stochastic perturbations tends to be suitably modeled by stochastic differential equations. This paper is concerned with the dynamic behaviors of a delay stochastic competitive system. We first obtain the global existence of a unique positive solution of system. Later, we show that the solution of system will be stochastically ultimate boundedness. However, large noises may make the system extinct exponentially with probability one. Also, sufficient conditions for the global attractivity of system are established. Finally, illustrated examples are given to show the effectiveness of the proposed criteria.
An Enhanced Distributed Scheme for WSNs
Authors: Sheltami Tarek R.
Published: March 2015

This paper investigates data processing schemes that define the distribution of decision making that affects system accuracy and energy consumption. There exist two typical schemes, namely: centralized and distributed schemes. In a centralized scheme, nodes collect samples and send them to a “fusion center.” This scheme provides optimal decision accuracy; however, it consumes considerable energy. In contrast, distributed schemes allow nodes to make local 1-bit decisions, which are sent to the fusion center to make the final decision. In a hybrid scheme, the network specifies the level of accuracy required for the whole system. This can be achieved by manipulating the scheme to work interchangeably as centralized or distributed. Most of the energy consumed is in the transmission process; therefore, this paper proposes an energy-saving hybrid scheme that focuses on optimizing transmission energy. In this proposed scheme, each node is able to alternate between centralized and decentralized scheme according to its location and path length. To validate the proposed approach, it is simulated and the results are compared with the hybrid scheme.
Study of RF Signal Attenuation of Human Heart
Authors: Sahu Kedar Nath , Naidu Challa Dhanunjaya , Satyam M. , Sankar K. Jaya
Published: March 2015

A study of ultrawideband pulse propagation modeling through human body for all frequencies from 0.1 to 10.5 GHz is presented. Reflection coefficient and signal attenuation are computed from the model considering the variation of heart dimension with respect to time unlike a fixed dimension of heart used in earlier models. The performance of cardiac activity is studied from the change of signal attenuation. This estimation may help in the design of a noninvasive diagnostic system using ultrawideband of frequencies.
TRAF1/C5but NotPTPRCVariants Are Potential Predictors of Rheumatoid Arthritis Response to Anti-Tumor Necrosis Factor Therapy
Authors: Canhão Helena , Rodrigues Ana Maria , Santos Maria José , Carmona-Fernandes Diana , Bettencourt Bruno F. , Cui Jing , Rocha Fabiana L. , Canas Silva José , Polido-Pereira Joaquim , Pereira Silva José Alberto , Costa José António , Araujo Domingos , Silva Cândida , Santos Helena , Duarte Cátia , Cáliz Rafael , Filipescu Ileana , Pimentel-Santos Fernando , Branco Jaime , Sainz Juan , Plenge Robert M. , Solomon Daniel H. , Bruges-Armas Jácome , Da Silva José António P. , Fonseca João Eurico , Karlson Elizabeth W.
Published: March 2015

Background. The aim of our work was to replicate, in a Southern European population, the association reported in Northern populations betweenPTPRClocus and response to anti-tumor necrosis factor (anti-TNF) treatment in rheumatoid arthritis (RA). We also looked at associations between five RA risk alleles and treatment response.Methods. We evaluated associations between anti-TNF treatment responses assessed by DAS28 change and by EULAR response at six months in 383 Portuguese patients. Univariate and multivariate linear and logistic regression analyses were performed. In a second step to confirm our findings, we pooled our population with 265 Spanish patients.Results. No association was found betweenPTPRCrs10919563 allele and anti-TNF treatment response, neither in Portuguese modeling for several clinical variables nor in the overall population combining Portuguese and Spanish patients. The minor allele for RA susceptibility, rs3761847 SNP inTRAF1/C5region, was associated with a poor response in linear and logistic univariate and multivariate regression analyses. No association was observed with the other allellic variants. Results were confirmed in the pooled analysis.Conclusion. This study did not replicate the association betweenPTPRCand the response to anti-TNF treatment in our Southern European population. We found thatTRAF1/C5risk RA variants potentially influence anti-TNF treatment response.
Difference in the Prognostic Significance of N-Terminal Pro-B-Type Natriuretic Peptide between Cardioembolic and Noncardioembolic Ischemic Strokes
Authors: Lee Seung-Jae , Lee Dong-Geun , Lim Dal-Soo , Hong Sukkeun , Park Jin-Sik
Published: March 2015

Background and Aim. Because B-type natriuretic peptide is a powerful predictor of heart failure, its capability to predict a fatal outcome in stroke might be limited to the cardioembolic stroke subtype. In this study, we attempt to ascertain the difference in the prognostic value of N-terminal pro-B-type natriuretic peptide (NT-proBNP) between cardioembolic and noncardioembolic stroke subgroups.Methods. 410 acute stroke patients were included. According to the presence of a cardioembolic source (CES), there were 221 patients with CES and 189 patients without CES. Logistic regression analysis was performed to ascertain the association between NT-proBNP and 6-month mortality/functional outcome in each group.Results. The mean age of our patients was 67.2 years (range, 18–97 years). NT-proBNP was a multivariate independent predictor of mortality in the CES group alone, whereas it was only a univariate predictor of 6-month mortality in the total patient and non-CES groups with its association disappearing in the multivariate model. In addition, it was only a univariate predictor of good functional outcome in all of the groups.Conclusions. Our data suggest that NT-proBNP can more reliably predict 6-month mortality in patients with cardioembolic stroke than in patients with other stroke subtypes.
Comparative Analysis of Classifiers for Developing an Adaptive Computer-Assisted EEG Analysis System for Diagnosing Epilepsy
Authors: Ahmad Malik Anas , Ayaz Yasar , Jamil Mohsin , Omer Gillani Syed , Rasheed Muhammad Babar , Imran Muhammad , Khan Nadeem Ahmed , Majeed Waqas , Javaid Nadeem
Published: March 2015

Computer-assisted analysis of electroencephalogram (EEG) has a tremendous potential to assist clinicians during the diagnosis of epilepsy. These systems are trained to classify the EEG based on the ground truth provided by the neurologists. So, there should be a mechanism in these systems, using which a system’s incorrect markings can be mentioned and the system should improve its classification by learning from them. We have developed a simple mechanism for neurologists to improve classification rate while encountering any false classification. This system is based on taking discrete wavelet transform (DWT) of the signals epochs which are then reduced using principal component analysis, and then they are fed into a classifier. After discussing our approach, we have shown the classification performance of three types of classifiers: support vector machine (SVM), quadratic discriminant analysis, and artificial neural network. We found SVM to be the best working classifier. Our work exhibits the importance and viability of a self-improving and user adapting computer-assisted EEG analysis system for diagnosing epilepsy which processes each channel exclusive to each other, along with the performance comparison of different machine learning techniques in the suggested system.
Characterization on Contacting Surfaces of MEMS Electrostatic Switches by SEM, EDXA, and XPS
Authors: Afinogenov I. A. , Zeltser I. A. , Trunin E. B. , Tolstoguzov A.
Published: March 2015

We focus on the origin and sources of surface contamination and defects causing the failure of MEMS electrostatic switches. The morphology, and elemental and chemical compositions of the contacting surfaces, conducting paths, and other parts of switches have been characterized by means of SEM, EDXA, and XPS in order to understand the difference between the data collected for the devices that had passed the electrical conductivity test and those found to be defective. C, O, Al, Ca, Ti, Cu, and some other impurities were detected on the details of defective switches. Contrariwise, the working switches were found to be clean, at least on the level of EDXA and XPS sensitivity. The main sources of surface contamination and defects were incompletely deleted sacrificial layers, substrate materials, and electrolytes employed for Rh plating of the contacts. The negative influence of foreign microparticles, especially alumina and copper oxides, on the conductivity and porosity of contacts was highlighted.
A Model-Driven Engineering Process for Autonomic Sensor-Actuator Networks
Authors: Vidal Carlos , Fernández-Sánchez Carlos , Díaz Jessica , Pérez Jennifer
Published: March 2015

Cyber-Physical Systems (CPS) are the next generation of embedded ICT systems designed to be aware of the physical environment by using sensor-actuator networks to provide users with a wide range of smart applications and services. Many of these smart applications are possible due to the incorporation of autonomic control loops that implement advanced processing and analysis of historical and real-time data measured by sensors; plan actions according to a set of goals or policies; and execute plans through actuators. The complexity of this kind of systems requires mechanisms that can assist the system's design and development. This paper presents a solution for assisting the design and development of CPS based on Model-Driven Development: MindCPS (doMaIN moDel for CPS) solution. MindCPS solution is based on a model that provides modelling primitives for explicitly specifying the autonomic behaviour of CPS and model transformations for automatically generating part of the CPS code. In addition to the automatic code generation, the MindCPS solution offers the possibility of rapidly configuring and developing the core behaviour of a CPS, even for nonsoftware engineers. The MindCPS solution has been put into practice to deploy a smart metering system in a demonstrator located at the Technical University of Madrid.
Orthogonal Projections Based on Hyperbolic and Sphericaln-Simplex
Authors: Savas Murat , Karliga Baki , Yakut Atakan T.
Published: March 2015

Orthogonal projection along a geodesic to the chosenk-plane is introduced using edge and Gram matrix of ann-simplex in hyperbolic or sphericaln-space. The distance from a point tok-plane is obtained by the orthogonal projection. It is also given the perpendicular foot from a point tok-plane of hyperbolic and sphericaln-space.
Gold Nanotheranostics: Photothermal Therapy and Imaging of Mucin 7 Conjugated Antibody Nanoparticles for Urothelial Cancer
Authors: Chen Chieh Hsiao , Wu Yi-Jhen , Chen Jia-Jin
Published: March 2015

Objective. To kill urothelial cancer cells while preserving healthy cells, this study used photothermal therapy (PTT). PTT techniques target urothelial cancer cells using gold nanoparticles (GNPs) and a green light laser.Materials and Methods. The GNPs were conjugated with anti-Mucin 7 antibodies, which acted as a probe for targeting tumor cells. Conjugated GNPs were exposed to a green light laser (532 nm) with sufficient thermal energy to kill the transitional cell carcinomas (TCCs).Results. According to our results, nanoparticles conjugated with Mucin 7 antibodies damaged all types of cancer cells (MBT2, T24, 9202, and 8301) at relatively low energy levels (i.e., 500 laser shots at 10 W/cm2in power, 1.6 Hz in frequency, and 300 ms in duration). Nonconjugated nanoparticles required 30 W/cm2or more to achieve the same effect. Cell damage was directly related to irradiation time and applied laser energy.Conclusions. The minimally invasive PTT procedure combined with Mucin 7 targeted GNPs is able to kill cancer cells and preserve healthy cells. The success of this treatment technique can likely be attributed to the lower amount of energy required to kill targeted cancer cells compared with that required to kill nontargeted cancer cells. Our in vitro pilot study yielded promising results; however, additional animal studies are required to confirm these findings.
Rhizogenesis in Cell Suspension Culture from Mango Ginger: A Source of Isosorbide and n-Hexadecanoic Acid
Authors: Soundar Raju Chellappan , Varutharaju Kandhan , Thilip Chandrasekaran , Aslam Abubakker , Shajahan Appakan
Published: March 2015

Curcuma amada Roxb. belongs to the monocotyledonous family Zingiberaceae. It is commonly known as mango ginger and used as a spice and valuable medicine. In this study, adventitious roots of C. amada have been successfully established from cell suspension culture. The highest percentage of adventitious root production was obtained from friable callus derived cell suspension culture. The culture conditions of adventitious root were optimized and the maximum adventitious root production was obtained in half strength MS liquid medium containing 0.3 mg L−1 IBA along with 3% of sucrose after 5 weeks of culture. Among the different initial inoculum density, the best culture condition for root growth occurred at 10 g FW of initial inoculum density. GC-MS analysis revealed that the in vitro raised adventitious roots containing two valuable bioactive compounds, isosorbide and n-hexadecanoic acid. The outcome of the present work will be helpful for the large scale cultivation of adventitious roots for the production of valuable bioactive compounds.
Three Novel Pathogenic Mutations in KATP Channel Genes and Somatic Imprinting Alterations of the 11p15 Region in Pancreatic Tissue in Patients with Congenital Hyperinsulinism
Authors: Lee Beom Hee , Lee Jin , Kim Jae-Min , Kang Minji , Kim Gu-Hwan , Choi Jin-Ho , Kim Jihun , Kim Chong Jai , Kim Dae-Yeon , Kim Seong-Chul , Yoo Han-Wook
Published: March 2015

Background/Aims: This study was performed to investigate the molecular pathology underlying focal and diffuse congenital hyperinsulinism (CHI). Methods: The ABCC8 and KCNJ11 genes were analyzed in 3 patients with focal CHI and in 1 patient with diffuse CHI. Immunohistochemistry, real-time PCR, methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) and microsatellite marker analyses of the 11p15 region were performed on both normal tissues and adenomatous hyperplasia lesions. Results: The 3 patients with focal CHI harbored paternally inherited ABCC8 or KCNJ11 mutations. Compound heterozygous ABCC8 mutations were identified in the patient with diffuse CHI. In the 3 patients with focal CHI, homozygous ABCC8 or KCNJ11 mutations were identified within the lesions. MLPA and real-time PCR revealed the presence of two copies of 11p15. MS-MLPA and microsatellite analyses demonstrated abnormal imprinting patterns and focal loss of maternal 11p13-15 within the lesions. In contrast, parental heterozygosity was preserved in the normal tissue. In the patient with diffuse CHI, the two ABCC8 mutations were conserved, and imprinting patterns at 11p15 were normal. Conclusions: The epigenetic alteration at the 11p15 region plays a central role in developing focal CHI by paternally derived mutations of the KATP channel and maternal allelic loss at this region. MS-MLPA and microsatellite analyses are useful to investigate the molecular etiology of CHI.
Periprocedural Cost-Effectiveness Analysis of Mechanical Thrombectomy for Acute Ischemic Stroke in the Stent Retriever Era
Authors: Kass-Hout Tareq , Kass-Hout Omar , Sun Chung-Huan , Kass-Hout Taha , Belagaje Samir R. , Anderson Aaron M. , Frankel Michael R. , Gupta Rishi , Nogueira Raul G.
Published: March 2015

Background: Early reperfusion is critical for favorable outcomes in acute ischemic stroke (AIS). Stent retrievers lead to faster and more complete reperfusion than previous technologies. Our aim is to compare the cost-effectiveness of stent retrievers to the previous mechanical thrombectomy devices. Methods: Retrospective review of endovascularly treated large-vessel AIS. Data from all consecutive patients who underwent thrombectomy from January 2012 through November 2012 were collected. Baseline characteristics, the total procedural cost, the rates of successful recanalization [modified thrombolysis in cerebral ischemia (mTICI) scores of 2b or 3], and the length of stay at the hospital were compared between the stent retriever (SR) and the non-stent retriever (NSR) groups. Results: After excluding the patients who underwent concomitant extracranial stenting (n = 22) or received intra-arterial tissue plasminogen activator only (n = 6), the entire cohort included 150 patients. The cost of the reperfusion procedure was significantly higher in the SR compared to the NSR group (USD 13,419 vs. 9,308, p <0.001). We were unable to demonstrate a statistically significant difference in the rates of mTICI 2b/3 reperfusion (81 vs. 74%, p = 0.337) or the length of stay (11.1 ± 9.1 vs. 12.8 ± 9.6 days, p = 0.260) amongst the SR and the NSR patients. Conclusion: The procedural costs of thrombectomy for AIS are increasing and account for the bulk of hospitalization reimbursement. The impact of these expenditures in the long-term sustainability of stroke centers deserves greater consideration. While it is likely that the SR technology results in higher rates of optimal reperfusion, better clinical outcomes, and shorter lengths of stay, larger studies are needed to prove its cost-effectiveness.
Biocompatibility Reduces Inflammation-Induced Apoptosis in Mesothelial Cells Exposed to Peritoneal Dialysis Fluid
Authors: Santamaría Beatriz , Ucero Alvaro Conrado , Benito-Martin Alberto , Vicent Maria Jesús , Orzáez Mar , Celdrán Angel , Selgas Rafael , Ruíz-Ortega Marta , Ortiz Alberto
Published: March 2015

Background/Aims: Peritonitis is a major complication that arises out of peritoneal dialysis (PD), leading to death and loss of mesothelium and peritoneal injury, which may impede PD. We studied the combined impact of inflammatory mediators and PD fluids on mesothelial cell death. Methods: Cultured human mesothelial cells. Results: Inflammatory cytokines (TNF-α and interferon-γ) cooperate with bioincompatible PD fluids containing high glucose degradation product (GDP) concentrations to promote mesothelial cell death. Thus, the inflammatory cytokine cocktail induced a higher rate of death in cells cultured in high GDP PD fluid than in low GDP PD fluid or cell culture medium (cell death expressed as % hypodiploid cells: TNF-α and interferon-γ in RPMI: 14.15 ± 1.68, TNF-α and interferon-γ in 4.25% low GDP PD fluid 13.16 ± 3.29, TNF-α and interferon-γ in 4.25% high GDP PD fluid 25.88 ± 2.18%, p < 0.05 vs. the other two groups). BclxL BH4 peptides, Apaf-1 inhibition or caspase inhibition failed to protect from apoptosis induced by the combination of inflammatory cytokines and bioincompatible PD fluids, although they protected from other forms of mesothelial cell apoptosis. Conclusion: Inflammation cooperates with high GDP PD fluids to promote mesothelial cell death, which is resistant to several therapeutic approaches. This information provides a framework for selection of PD fluid during peritonitis.
Early Experience with Laparoscopic Lavage in Acute Complicated Diverticulitis
Authors: Horesh Nir , Zbar Andrew P. , Nevler Avinoam , Haim Nadav , Gutman Mordechai , Zmora Oded
Published: March 2015

Background: Contemporary surgical management of complicated diverticulitis is controversial. Traditionally, the gold standard has been resection and colostomy, but recently peritoneal lavage and drainage without resection in cases of purulent peritonitis have been suggested. This study aims to review our initial experience with laparoscopic peritoneal lavage for complicated diverticulitis. Methods: Retrospective review of all patients who underwent emergent peritoneal lavage and drainage for acute complicated diverticulitis. Results: Five-hundred-thirty-eight patients admitted for acute diverticulitis between 2007 and 2012 were recorded in the database. Thirty seven underwent emergent surgery of which 10 had peritoneal lavage and drainage without colonic resection for complicated diverticulitis causing peritonitis. Peritoneal lavage and drainage resulted in the resolution of acute symptoms in all cases. In long-term follow-up, 3 (30%) patients required elective resection owing to symptomatic disease, two of these due to recurrent diverticulitis, and one owing to complicated fistula following the procedure. Conclusion: Peritoneal lavage is a feasible option for complicated diverticulitis with purulent non-fecal peritonitis, but a significant portion of the patients may require elective resection. Comparative studies with emergent resection are needed to determine the role of peritoneal lavage in complicated diverticulitis.
Phosphorylation of Cardiac Myosin-Binding Protein-C Is a Critical Mediator of Diastolic Function
Authors: Rosas Paola C. , Liu Yang , Abdalla Mohamed I. , Thomas Candice M. , Kidwell David T. , Dusio Giuseppina F. , Mukhopadhyay Dhriti , Kumar Rajesh , Baker Kenneth M. , Mitchell Brett M. , Powers Patricia A. , Fitzsimons Daniel P. , Patel Bindiya G. , Warren Chad M. , Solaro R. John , Moss Richard L. , Tong Carl W.
Published: March 2015

Background—

Heart failure (HF) with preserved ejection fraction (HFpEF) accounts for ≈50% of all cases of HF and currently has no effective treatment. Diastolic dysfunction underlies HFpEF; therefore, elucidation of the mechanisms that mediate relaxation can provide new potential targets for treatment. Cardiac myosin-binding protein-C (cMyBP-C) is a thick filament protein that modulates cross-bridge cycling rates via alterations in its phosphorylation status. Thus, we hypothesize that phosphorylated cMyBP-C accelerates the rate of cross-bridge detachment, thereby enhancing relaxation to mediate diastolic function.

Methods and Results—

We compared mouse models expressing phosphorylation-deficient cMyBP-C(S273A/S282A/S302A)–cMyBP-C(t3SA), phosphomimetic cMyBP-C(S273D/S282D/S302D)–cMyBP-C(t3SD), and wild-type-control cMyBP-C(tWT) to elucidate the functional effects of cMyBP-C phosphorylation. Decreased voluntary running distances, increased lung/body weight ratios, and increased brain natriuretic peptide levels in cMyBP-C(t3SA) mice demonstrate that phosphorylation deficiency is associated with signs of HF. Echocardiography (ejection fraction and myocardial relaxation velocity) and pressure/volume measurements (−d
P
/d
t
min
, pressure decay time constant
τ
-Glantz, and passive filling stiffness) show that cMyBP-C phosphorylation enhances myocardial relaxation in cMyBP-C(t3SD) mice, whereas deficient cMyBP-C phosphorylation causes diastolic dysfunction with HFpEF in cMyBP-C(t3SA) mice. Simultaneous force and [Ca
2+
]
i
measurements on intact papillary muscles show that enhancement of relaxation in cMyBP-C(t3SD) mice and impairment of relaxation in cMyBP-C(t3SA) mice are not because of altered [Ca
2+
]
i
handling, implicating that altered cross-bridge detachment rates mediate these changes in relaxation rates.

Conclusions—

cMyBP-C phosphorylation enhances relaxation, whereas deficient phosphorylation causes diastolic dysfunction and phenotypes resembling HFpEF. Thus, cMyBP-C is a potential target for treatment of HFpEF.
Agency and Responsibility in Aristotle’s Eudemian Ethics
Authors: Müller Jozef
Published: March 2015

I argue that Aristotle’s account of voluntary action focuses on the conditions under which one is the efficient cause of one’s actions qua individual. I also argue that Aristotle’s conception of the efficient cause of an action brings in certain normative features which support evaluative judgments and the practice of praise and blame even in the case of non-rational animals. In the case of rational agents, this practice involves a further normative layer: they can be praised or blamed not only for acting in a certain way, but also for being, and having become, individuals of a certain sort.