bluuebunny/crossref_metadata_2025_split huggingface dataset:
Parametric Equations for Maximum Stresses in Cylindrical Vessels Subjected to Thermal Expansion Loading
Authors: Ong L. S. , Cheung J. S. T. , Ng H. W. , Tooth A. S. 
Published: December 2014

This paper derives a set of parametric equations for finding the maximum stresses developed in the cylindrical vessel which is supported by two saddles firmly secured to the foundation and subjected to thermal expansion loading. Three types of stresses are considered: maximum stress intensity, maximum circumferential stress and maximum axial stress. The maximum stresses in the vessel are found to be governed by the height and width of the saddle, the spacing between the two supports and the relative structural rigidity between the support and the vessel. This paper is an extension of the work reported by Tooth, et.al (1996).
Using a least square curve fitting procedure, parametric equations for the maximum stresses developed in the vessel have been established. Raw data used for the curve fitting were obtained from a carefully-planned finite element study which covers a wide range of key dimensions. A total of 900 finite element runs have been performed.
The derived parametric equations are subsequently validated against the raw data and their error bounds are established. In all cases the maximum errors are found to be within 20%. The established parametric equations can be used directly in design calculations. The curve fitting procedure outlined in this paper has wide application for any set of generated or measured data.
Interfacing Virtual Reality, CFD and the Internet
Authors: Freeman David J. 
Published: December 2014

Computational Fluid Dynamics (CFD) is a valuable tool for the process and petroleum industries. CFD reduces development timescales and costs by replacing expensive and lengthy laboratory investigation with numerical predictions of processes.
However, there are several reasons why some companies are unwilling to use CFD. These include the cost of the software and hardware, the need for in-house CFD expertise and the time required to solve complex simulations.
CHAM has developed a solution to these problems, in the form of a Virtual Reality Interface linked via the Internet to powerful parallel-processor computers. Virtual reality makes CFD accessible to non-CFD experts and allows the engineer to concentrate on the solution of his problem. Remote computing makes it possible to access from a PC the necessary computing power to solve the problem.
Several examples will be shown, demonstrating the application and benefits of the PHOENICS-VR interface and the advantages of remote computing to the process and petroleum industries.
Vertical Design HRSG With Natural Circulation Successfull in Operation
Authors: Rath D. , Koller A. 
Published: December 2014

At the beginning of the Sixties the concept of Combined Cycle Power Plants (CCPP) was introduced to the market in parallel to the Standard Steam Power Plants.
Based on the experience of Waste Heat Boilers, built behind the blast oxygen furnaces of steel mills, Heat Recovery Steam Generators (HRSG) with forced or assisted circulation as well as of the natural circulation type were developed.
The latest version of HRSG’s, the vertical type with heating surfaces horizontally arranged and natural circulation only, was put into succesfull operation in 1995.
Development and experiences shall be presented.
The Economics of Firing Heavy Fuels in Utility Gas Turbines
Authors: Singh R. , Baker M. S. 
Published: December 2014

Heavy fuel oil is of interest for firing in utility gas turbine and combined cycle plant, particularly in the developing economies of Asia and Latin America. There are few detailed studies published, which justify in commercial terms the use of heavy fuels in utility gas turbine plant or indicate the scenarios when this should be considered. Whilst this technology/fuel combination is mature and can be considered proven, awareness of the option and the technical and commercial implications is not widespread.
This paper outlines the technical and commercial implications of firing heavy fuels in open cycle peaking and base load combined cycle plant. An economic comparison is made with the alternative fuel and technology options. It is demonstrated that firing heavy fuels in base load combined cycle plant can yield significant cost savings compared to using alternative technologies and liquid fuels, provided the emissions limits are not restrictive.
Pharmacokinetic-Pharmacodynamic Model To Evaluate Intramuscular Tetracycline Treatment Protocols To Prevent Antimicrobial Resistance in Pigs
Authors: Ahmad Amais , Græsbøll Kaare , Christiansen Lasse Engbo , Toft Nils , Matthews Louise , Nielsen Søren Saxmose 
Published: December 2014

ABSTRACTHigh instances of antimicrobial resistance are linked to both routine and excessive antimicrobial use, but excessive or inappropriate use represents an unnecessary risk. The competitive growth advantages of resistant bacteria may be amplified by the strain dynamics; in particular, the extent to which resistant strains outcompete susceptible strains under antimicrobial pressure may depend not only on the antimicrobial treatment strategies but also on the epidemiological parameters, such as the composition of the bacterial strains in a pig. This study evaluated how variation in the dosing protocol for intramuscular administration of tetracycline and the composition of bacterial strains in a pig affect the level of resistance in the intestine of a pig. Predictions were generated by a mathematical model of competitive growth ofEscherichia colistrains in pigs under specified plasma concentration profiles of tetracycline. All dosing regimens result in a clear growth advantage for resistant strains. Short treatment duration was found to be preferable, since it allowed less time for resistant strains to outcompete the susceptible ones. Dosing frequency appeared to be ineffective at reducing the resistance levels. The number of competing strains had no apparent effect on the resistance level during treatment, but possession of fewer strains reduced the time to reach equilibrium after the end of treatment. To sum up, epidemiological parameters may have more profound influence on growth dynamics than dosing regimens and should be considered when designing improved treatment protocols.
Preclinical Activity of VX-787, a First-in-Class, Orally Bioavailable Inhibitor of the Influenza Virus Polymerase PB2 Subunit
Authors: Byrn Randal A. , Jones Steven M. , Bennett Hamilton B. , Bral Chris , Clark Michael P. , Jacobs Marc D. , Kwong Ann D. , Ledeboer Mark W. , Leeman Joshua R. , McNeil Colleen F. , Murcko Mark A. , Nezami Azin , Perola Emanuele , Rijnbrand Rene , Saxena Kumkum , Tsai Alice W. , Zhou Yi , Charifson Paul S. 
Published: December 2014

ABSTRACT

VX-787 is a novel inhibitor of influenza virus replication that blocks the PB2 cap-snatching activity of the influenza viral polymerase complex. Viral genetics and X-ray crystallography studies provide support for the idea that VX-787 occupies the 7-methyl GTP (m
7
GTP) cap-binding site of PB2. VX-787 binds the cap-binding domain of the PB2 subunit with a

K
D

(dissociation constant) of 24 nM as determined by isothermal titration calorimetry (ITC). The cell-based EC
50
(the concentration of compound that ensures 50% cell viability of an uninfected control) for VX-787 is 1.6 nM in a cytopathic effect (CPE) assay, with a similar EC
50
in a viral RNA replication assay. VX-787 is active against a diverse panel of influenza A virus strains, including H1N1pdm09 and H5N1 strains, as well as strains with reduced susceptibility to neuraminidase inhibitors (NAIs). VX-787 was highly efficacious in both prophylaxis and treatment models of mouse influenza and was superior to the neuraminidase inhibitor, oseltamivir, including in delayed-start-to-treat experiments, with 100% survival at up to 96 h postinfection and partial survival in groups where the initiation of therapy was delayed up to 120 h postinfection. At different doses, VX-787 showed a 1-log to >5-log reduction in viral load (relative to vehicle controls) in mouse lungs. Overall, these favorable findings validate the PB2 subunit of the viral polymerase as a drug target for influenza therapy and support the continued development of VX-787 as a novel antiviral agent for the treatment of influenza infection.
Identification and Characterization of Rvs162/Rvs167-3, a Novel N-BAR Heterodimer in the Human Fungal Pathogen Candida albicans
Authors: Gkourtsa Areti , van den Burg Janny , Strijbis Karin , Avula Teja , Bijvoets Sietske , Timm Dave , Hochstenbach Frans , Distel Ben 
Published: December 2014

ABSTRACT

Membrane reshaping resides at the core of many important cellular processes, and among its mediators are the BAR (Bin, Amphiphysin, Rvs) domain-containing proteins. We have explored the diversity and function of the Rvs BAR proteins in
Candida albicans
and identified a novel family member, Rvs167-3 (orf19.1861). We show that Rvs167-3 specifically interacts with Rvs162 to form a stable BAR heterodimer able to bind liposomes
in vitro
. A second, distinct heterodimer is formed by the canonical BAR proteins Rvs161 and Rvs167. Purified Rvs161/Rvs167 complex also binds liposomes, indicating that
C. albicans
expresses two functional BAR heterodimers. We used live-cell imaging to localize green fluorescent protein (GFP)-tagged Rvs167-3 and Rvs167 and show that both proteins concentrate in small cortical spots. However, while Rvs167 strictly colocalizes with the endocytic marker protein Abp1, we do not observe any colocalization of Rvs167-3 with sites of endocytosis marked by Abp1. Furthermore, the
rvs167-3
Δ/Δ mutant is not defective in endocytosis and strains lacking Rvs167-3 or its partner Rvs162 do not display increased sensitivity to high salt concentrations or decreased cell wall integrity, phenotypes which have been observed for
rvs167
Δ/Δ and
rvs161
Δ/Δ strains and which are linked to endocytosis defects. Taken together, our results indicate different roles for the two BAR heterodimers in
C. albicans
: the canonical Rvs161/Rvs167 heterodimer functions in endocytosis, whereas the novel Rvs162/Rvs167-3 heterodimer seems not to be involved in this process. Nevertheless, despite their different roles, our phenotypic analysis revealed a genetic interaction between the two BAR heterodimers, suggesting that they may have related but distinct membrane-associated functions.
Salt-Inducible Kinase 2 Regulates Mitotic Progression and Transcription in Prostate Cancer
Authors: Bon Hélène , Wadhwa Karan , Schreiner Alexander , Osborne Michelle , Carroll Thomas , Ramos-Montoya Antonio , Ross-Adams Helen , Visser Matthieu , Hoffmann Ralf , Ahmed Ahmed Ashour , Neal David E. , Mills Ian G. 
Published: December 2014

Abstract
Salt-inducible kinase 2 (SIK2) is a multifunctional kinase of the AMPK family that plays a role in CREB1-mediated gene transcription and was recently reported to have therapeutic potential in ovarian cancer. The expression of this kinase was investigated in prostate cancer clinical specimens. Interestingly, auto-antibodies against SIK2 were increased in the plasma of patients with aggressive disease. Examination of SIK2 in prostate cancer cells found that it functions both as a positive regulator of cell-cycle progression and a negative regulator of CREB1 activity. Knockdown of SIK2 inhibited cell growth, delayed cell-cycle progression, induced cell death, and enhanced CREB1 activity. Expression of a kinase-dead mutant of SIK2 also inhibited cell growth, induced cell death, and enhanced CREB1 activity. Treatment with a small-molecule SIK2 inhibitor (ARN-3236), currently in preclinical development, also led to enhanced CREB1 activity in a dose- and time-dependent manner. Because CREB1 is a transcription factor and proto-oncogene, it was posited that the effects of SIK2 on cell proliferation and viability might be mediated by changes in gene expression. To test this, gene expression array profiling was performed and while SIK2 knockdown or overexpression of the kinase-dead mutant affected established CREB1 target genes; the overlap with transcripts regulated by forskolin (FSK), the adenylate cyclase/CREB1 pathway activator, was incomplete.
Implications: This study demonstrates that targeting SIK2 genetically or therapeutically will have pleiotropic effects on cell-cycle progression and transcription factor activation, which should be accounted for when characterizing SIK2 inhibitors. Mol Cancer Res; 13(4); 620–35. ©2014 AACR.
Sudden Advanced Illness
Authors: Barnett Michael D. , Williams Beverly R. , Tucker Rodney O. 
Published: December 2014

Background: End-of-life discussions in critically-ill patients with acute surgical conditions may be rushed and occur earlier during hospitalization. This study explores the concept of sudden advanced illness (SAI) and its relevance to patients requiring Palliative and Surgical Critical Care. Methods: Semi-structured interviews were completed with 16 physicians, querying each about (1) definitional components, (2) illustrative cases, and (3) comfort with SAI. Analysis was done by grounded theory. Results: SAI was characterized as unforeseen, emerging abruptly and producing devastating injury, often in healthy, younger patients. There is (1) prognostic uncertainty, (2) loss of capacity, and (3) unprepared surrogate decision-making. Cases are emotionally-charged and often personal. Conclusion: The emerging concept of SAI is important for understanding how Palliative Care can enhance care for this subset of patients.
Schwannomatosis on a Single Foot
Authors: Min Hak-Jin , Kim Ki Chun , Jun Sung Han , Lee Young Gun 
Published: December 2014

Schwannomatosis has been recently recognized as the third major type of neurofibromatosis. It causes multiple schwannomas without the vestibular tumors that are diagnostic of neurofibromatosis type 2. Schwannoma is rarely found in the foot, and it is still rarer to find multiple schawannomas in a single peripheral nerve on the foot. In this article, we describe a case of schwannomatosis case on a single foot. Levels of Evidence: Case report, Level IV
Evidence of an oncogenic role of aberrant TOX activation in cutaneous T-cell lymphoma
Authors: Huang Yuanshen , Su Ming-Wan , Jiang Xiaoyan , Zhou Youwen 
Published: December 2014

Key Points
TOX is aberrantly expressed in primary Sézary cells and its levels correlate with increased risk of disease-specific mortality. TOX knockdown promotes apoptosis and reduces cell proliferation in CTCL cells, partially through inducing p27 and p57.
Elafin is downregulated during breast and ovarian tumorigenesis but its residual expression predicts recurrence
Authors: Caruso Joseph A , Karakas Cansu , Zhang Jing , Yi Min , Albarracin Constance , Sahin Aysegul , Bondy Melissa , Liu Jinsong , Hunt Kelly K , Keyomarsi Khandan 
Published: December 2014

Abstract
Introduction
Elafin is an endogenous serine protease inhibitor. The majority of breast cancer cell lines lack elafin expression compared to human mammary epithelial cells. In this study, we hypothesized that elafin is downregulated during breast and ovarian tumorigenesis.

Methods
We examined elafin expression by immunohistochemistry (IHC) in specimens of normal breast tissue (n = 24), ductal carcinoma in situ (DCIS) (n = 54), and invasive breast cancer (n = 793). IHC analysis of elafin expression was also performed in normal fallopian tube tissue (n = 20), ovarian cystadenomas (n = 9), borderline ovarian tumors (n = 21), and invasive ovarian carcinomas (n = 216). To understand the significance of elafin in luminal breast cancer cell lines, wild-type or M25G elafin (lacking the protease inhibitory function) were exogenously expressed in MCF-7 and T47D cells.

Results
Elafin expression was downregulated in 24% of DCIS and 83% of invasive breast tumors when compared to elafin expression in the normal mammary epithelium. However, the presence of elafin-positive cells in invasive breast tumors, even at low frequency, correlated with poor recurrence-free survival (RFS), reduced overall survival (OS), and clinicopathological markers of aggressive tumor behavior. Elafin-positive cells were an especially strong and independent prognostic marker of reduced RFS in IHC-defined luminal A-like tumors. Elafin was also downregulated in 33% of ovarian cystadenomas, 43% of borderline ovarian tumors, and 86% of invasive ovarian carcinomas when compared to elafin expression in the normal fallopian tube. In ovarian tumors, elafin-positive cells were correlated with reduced RFS, OS and disease-specific survival (DSS) only in stage I/II patients and not in stage III/IV patients. Notably, exogenous expression of elafin or elafin M25G in the luminal breast cancer cell lines MCF-7 and T47D significantly decreased cell proliferation in a protease inhibitory domain-independent manner.

Conclusions
Elafin predicts poor outcome in breast and ovarian cancer patients and delineates a subset of endocrine receptor-positive breast cancer patients susceptible to recurrence who could benefit from more aggressive intervention. Our in vitro results suggest that elafin arrests luminal breast cancer cells, perhaps suggesting a role in tumor dormancy.
Neutrophil homeostasis and inflammation: novel paradigms from studying periodontitis
Authors: Hajishengallis George , Chavakis Triantafyllos , Hajishengallis Evlambia , Lambris John D 
Published: December 2014

Abstract
Once viewed as simply antibacterial effector cells packed with antimicrobials, neutrophils are now increasingly appreciated for their regulatory roles in immunity and inflammation. The homeostatic regulation of neutrophils is thus crucial for optimal operation of the immune system. An attractive model to understand mechanistically the role of neutrophils is periodontitis, an oral inflammatory disease that is particularly sensitive to neutrophil alterations in numbers or function. The recruitment and proper activation of neutrophils are largely dependent on leukocyte integrins and complement. This review discusses how these processes are affected by host genetic or microbial factors leading to the development of periodontitis. For instance, both hypo- and hyper-recruitment of neutrophils as a result of deficiencies in the expression of β2 integrins or their negative regulators, respectively, causes unwarranted IL-17-dependent inflammatory bone loss. Moreover, microbial hijacking of C5aR (CD88) signaling in neutrophils impairs their antimicrobial function while promoting destructive inflammatory responses. These studies not only support the concept that neutrophil homeostasis is key to periodontal health but also reveal promising, new therapeutic targets as discussed in the review.
Context-dependent role of IL-18 in cancer biology and counter-regulation by IL-18BP
Authors: Fabbi Marina , Carbotti Grazia , Ferrini Silvano 
Published: December 2014

AbstractIL-18 is a proinflammatory and immune regulatory cytokine, member of the IL-1 family. IL-18 was initially identified as an IFN-γ-inducing factor in T and NK cells, involved in Th1 responses. IL-18 is produced as an inactive precursor (pro-IL-18) that is enzymatically processed into a mature form by Casp1. Different cells, such as macrophages, DCs, microglial cells, synovial fibroblasts, and epithelial cells, express pro-IL-18, and the production of bioactive IL-18 is mainly regulated at the processing level. PAMP or DAMP molecules activate inflammasomes, which trigger Casp1 activation and IL-18 conversion. The natural inhibitor IL-18BP, whose production is enhanced by IFN-γ and IL-27, further regulates IL-18 activity in the extracellular environment. Inflammasomes and IL-18 represent double-edged swords in cancer, as their activation may promote tumor development and progression or oppositely, enhance anti-tumor immunity and limit tumor growth. IL-18 has shown anti-tumor activity in different preclinical models of cancer immunotherapy through the activation of NK and/or T cell responses and has been tested in clinical studies in cancer patients. However, the dual role of IL-18 in different experimental tumor models and human cancers raises critical issues on its therapeutic use in cancer. This review will summarize the biology of the IL-18/IL-18R/IL-18BP system and will address the role of IL-18 and its inhibitor, IL-18BP, in cancer biology and immunotherapy.
Allogeneic Stem-Cell Transplantation in Patients With NPM1-Mutated Acute Myeloid Leukemia: Results From a Prospective Donor Versus No-Donor Analysis of Patients After Upfront HLA Typing Within the SAL-AML 2003 Trial
Authors: Röllig Christoph , Bornhäuser Martin , Kramer Michael , Thiede Christian , Ho Anthony D. , Krämer Alwin , Schäfer-Eckart Kerstin , Wandt Hannes , Hänel Mathias , Einsele Hermann , Aulitzky Walter E. , Schmitz Norbert , Berdel Wolfgang E. , Stelljes Matthias , Müller-Tidow Carsten , Krug Utz , Platzbecker Uwe , Wermke Martin , Baldus Claudia D. , Krause Stefan W. , Stölzel Friedrich , von Bonin Malte , Schaich Markus , Serve Hubert , Schetelig Johannes , Ehninger Gerhard 
Published: December 2014

Purpose The presence of a mutated nucleophosmin-1 gene (NPM1mut) in acute myeloid leukemia (AML) is associated with a favorable prognosis. To assess the predictive value with regard to allogeneic stem-cell transplantation (SCT), we compared the clinical course of patients with NPM1mut AML eligible for allogeneic SCT in a donor versus no-donor analysis. Patients and Methods Of 1,179 patients with AML (age 18 to 60 years) treated in the Study Alliance Leukemia AML 2003 trial, we identified all NPM1mut patients with an intermediate-risk karyotype. According to the trial protocol, patients were intended to receive an allogeneic SCT if an HLA-identical sibling donor was available. Patients with no available donor received consolidation or autologous SCT. We compared relapse-free survival (RFS) and overall survival (OS) depending on the availability of a suitable donor. Results Of 304 eligible patients, 77 patients had a sibling donor and 227 had no available matched family donor. The 3-year RFS rates in the donor and no-donor groups were 71% and 47%, respectively (P = .005); OS rates were 70% and 60%, respectively (P = .114). In patients with normal karyotype and no FLT3 internal tandem duplication (n = 148), the 3-year RFS rates in the donor and no-donor groups were 83% and 53%, respectively (P = .004); and the 3-year OS rates were 81% and 75%, respectively (P = .300). Conclusion Allogeneic SCT led to a significantly prolonged RFS in patients with NPM1mut AML. The absence of a statistically significant difference in OS is most likely a result of the fact that NPM1mut patients who experienced relapse responded well to salvage treatment. Allogeneic SCT in first remission has potent antileukemic efficacy and is a valuable treatment option in patients with NPM1mut AML with a sibling donor.