bluuebunny/crossref_metadata_2025_split huggingface dataset:
Porcine Reproductive and Respiratory Syndrome Virus Induces Interleukin-15 through the NF-κB Signaling Pathway
Authors: Fu Yi , Quan Rong , Zhang Hexiao , Hou Jun , Tang Jun , Feng Wen-hai 
Published: May 2012

ABSTRACTPorcine reproductive and respiratory syndrome virus (PRRSV) mainly infects macrophages/dendritic cells and modulates cytokine expression in these cells. Interleukin-15 (IL-15) is a pleiotropic cytokine involved in wide range of biological activities. It has been shown to be essential for the generation, activation, and proliferation of NK and NKT cells and for the survival and activation of CD8+effector and memory T cells. In this study, we discovered that PRRSV infection upregulated IL-15 production at both the mRNA and protein levels in porcine alveolar macrophages (PAMs), blood monocyte-derived macrophages (BMo), and monocyte-derived dendritic cells (DCs). We subsequently demonstrated that the NF-κB signaling pathway was essential for PRRSV infection-induced IL-15 production. First, addition of an NF-κB inhibitor drastically reduced PRRSV infection-induced IL-15 production. We then found that NF-κB was indeed activated upon PRRSV infection, as evidenced by IκB phosphorylation and degradation. Moreover, we revealed an NF-κB binding motif in the cloned porcine IL-15 (pIL-15) promoter, deletion of which abrogated the pIL-15 promoter activity in PRRSV-infected alveolar macrophages. In addition, we demonstrated that PRRSV nucleocapsid (N) protein had the ability to induce IL-15 production in porcine alveolar macrophage cell line CRL2843 by transient transfection, which was mediated by its multiple motifs, and it also activated NF-κB. These data indicated that PRRSV infection-induced IL-15 production was likely through PRRSV N protein-mediated NF-κB activation. Our findings provide new insights into the molecular mechanisms underling the IL-15 production induced by PRRSV infection.
The relationship between executive dysfunction and post-stroke mortality: a population-based cohort study
Authors: Wiberg Bernice , Kilander Lena , Sundström Johan , Byberg Liisa , Lind Lars 
Published: May 2012

ObjectivesTo study the associations of pre-stroke cognitive performance with mortality after first-ever stroke or transient ischaemic attack (TIA).DesignA prospective cohort study.Setting and participantsIn participants having first-ever stroke or TIA during up to 14 years of post-test follow-up (n=155), we investigated the associations of pre-stroke variables and cognitive test results with post-stroke survival. The study is based on those participants of the Uppsala Longitudinal Study of Adult Men who performed cognitive function tests at approximately age 70 (n=919).Primary outcome measuresMortality after first-ever stroke or TIA related to pre-stroke executive performance.ResultsEighty-four (54%) of the first-ever stroke/TIA patients died under a median follow-up of 2.5 years after the event. In Cox proportional hazard analyses adjusting for age, education, social group and traditional stroke risk factors, poor performance in Trail Making Test (TMT)-A was related to mortality (HR 1.88 per SD, 95% CI 1.31 to 2.71, p=0.001). The risk of mortality was approximately threefold higher in the highest tertile compared with the lowest tertile (HR TMT-A= 2.90 per SD, 95% CI 1.24 to 6.77, p=0.014). A similar pattern was seen for TMT-B, but Mini-Mental State Examination results were not related to risk of post-stroke mortality.ConclusionExecutive performance measured by TMT-A and -B before stroke was independently associated with long-term risk of mortality, after first-ever stroke or TIA in a population-based study of older men.
RG FLOW OF TRANSPORT QUANTITIES
Authors: LEE BUM-HOON , PAL SHESANSU SEKHAR , SIN SANG-JIN 
Published: May 2012

The RG flow equation of various transport quantities are studied in arbitrary space–time dimensions, in the fixed as well as fluctuating background geometry both for the Maxwellian and DBI type of actions. The regularity condition on the flow equation of the conductivity at the horizon for the DBI action reproduces naturally the leading order result of Hartnoll et al. [J. High Energy Phys. 04, 120 (2010)]. Motivated by the result of van der Marel et al. [Science 425, 271 (2003], we studied, analytically, the conductivity versus frequency plane by dividing it into three distinct parts: ω < T, ω > T and ω ≫ T. In order to compare, we choose (3+1)-dimensional bulk space–time for the computation of the conductivity. In the ω < T range, the conductivity does not show up the Drude like form in any space–time dimensions. In the ω > T range and staying away from the horizon, for the DBI action with unit dynamical exponent, nonzero magnetic field and charge density, the conductivity goes as ω-2/3, whereas the phase of the conductivity, goes as, arctan ( Im σxx/ Re σxx) = π/6 and arctan ( Im σxy/ Re σxy) = -π/3. There exists a universal quantity at the horizon that is the phase angle of conductivity, which either vanishes or an integral multiple of π. Furthermore, we calculate the temperature dependence to the thermoelectric and the thermal conductivity at the horizon. The charge diffusion constant for the DBI action is studied.
Improving Mass Transfer to Soften Tissues by Pulsed Electric Fields: Fundamentals and Applications
Authors: Puértolas E. , Luengo E. , Álvarez I. , Raso J. 
Published: May 2012

The mass transfer phenomenon occurs in many operations of the food industry with the purpose of obtaining a given substance of interest, removing water from foods, or introducing a given substance into the food matrix. Pretreatments that modify the permeability of the cell membranes, such as grinding, heating, or enzymatic treatment, enhance the mass transfer. However, these techniques may require a significant amount of energy and can cause losses of valuable food compounds.Pulsed electric field (PEF) technology is a nonthermal processing method that causes permeabilization of cell membranes using low energy requirements and minimizing quality deterioration of the food compounds. Many practical applications of PEF for enhancing mass transfer in the food industry have been investigated. The purpose of this chapter is to give an overview of the state of the art of application of PEF for improving mass transfer in the food industry.
The T-cell Receptor Repertoire of Tumor-Infiltrating Regulatory T Lymphocytes Is Skewed Toward Public Sequences
Authors: Sainz-Perez Alexander , Lim Annick , Lemercier Brigitte , Leclerc Claude 
Published: May 2012

AbstractThe accumulation of CD4+ T regulatory cells (Treg) in tumor tissue is a widely described phenomenon in mouse models and in human cancer patients. Understanding the mechanisms by which Treg migrate and accumulate in tumors is important because they strongly influence the potential efficacy of many immunotherapies. In this study, we used immunoscope technology to analyze the T-cell receptor (TCR) repertoire of tumor-infiltrating T cells in non-TCR transgenic mice. Both tumor-infiltrating Tregs and T effector cells (Teff) displayed sequence profiles in the CDR3 region that were characteristic of biased repertoires seen during clonal cell expansions, implying that strong T-cell responses have occurred within the tumor tissue. By comparing the TCR sequences of tumor-infiltrating Tregs, we obtained evidence of the presence of so-called public TCR sequences that are common to many individuals yet were tumor-specific in nature. Such comparisons also suggested that the Treg–Teff conversion process is not an active process at the tumor site or tumor-draining lymph nodes. Our findings strongly suggest that Treg infiltration of tumor tissue is followed by marked proliferation of a few dominant T-cell clones in the tumor. Cancer Res; 72(14); 3557–69. ©2012 AACR.
Sensitivity of Glioblastomas to Clinically Available MEK Inhibitors Is Defined by Neurofibromin 1 Deficiency
Authors: See Wendy L. , Tan I-Li , Mukherjee Joydeep , Nicolaides Theodore , Pieper Russell O. 
Published: May 2012

Abstract
Loss of neurofibromin 1 (NF1) leads to hyperactivation of RAS, which in turn signals through the RAF/MEK/ERK and phosphoinositide 3-kinase (PI3K)/mTOR pathways to regulate cell growth and survival. Because NF1-deficient acute myeloid leukemias are sensitive to MEK inhibitors, we investigated here whether NF1-deficient glioblastoma multiforme (GBM) would respond to MEK inhibition. In 19 GBM cell lines, we found that treatment with the clinically available MEK inhibitors PD0325901 or AZD6244 decreased levels of phospho-ERK, the downstream effector of MEK, regardless of NF1 status. However, growth inhibition occurred only in a subset of NF1-deficient cells, in association with decreased levels of cyclin D1, increased levels of p27, and G1 arrest. As a single agent, PD0325901 suppressed the growth of NF1-deficient, MEK inhibitor–sensitive cells in vivo as well. Mechanistically, NF1-deficient, MEK inhibitor–sensitive cells were dependent upon the RAF/MEK/ERK pathway for growth and did not activate the PI3K pathway as a mechanism of acquired resistance. Importantly, NF1-deficient cells intrinsically resistant to MEK inhibition were sensitized by the addition of the dual PI3K/mTOR inhibitor PI-103. Taken together, our findings indicate that a subset of NF1-deficient GBMs may respond to MEK inhibitors currently being tested in clinical trials. Cancer Res; 72(13); 3350–9. ©2012 AACR.
Phase I Trial of a Glypican-3–Derived Peptide Vaccine for Advanced Hepatocellular Carcinoma: Immunologic Evidence and Potential for Improving Overall Survival
Authors: Sawada Yu , Yoshikawa Toshiaki , Nobuoka Daisuke , Shirakawa Hirofumi , Kuronuma Toshimitsu , Motomura Yutaka , Mizuno Shoichi , Ishii Hiroshi , Nakachi Kohei , Konishi Masaru , Nakagohri Toshio , Takahashi Shinichiro , Gotohda Naoto , Takayama Tadatoshi , Yamao Kenji , Uesaka Katsuhiko , Furuse Junji , Kinoshita Taira , Nakatsura Tetsuya 
Published: May 2012

Abstract
Purpose: The carcinoembryonic antigen glypican-3 (GPC3) is an ideal target of anticancer immunotherapy against hepatocellular carcinoma (HCC). In this nonrandomized, open-label, phase I clinical trial, we analyzed the safety and efficacy of GPC3 peptide vaccination in patients with advanced HCC.
Experimental Design: Thirty-three patients with advanced HCC underwent GPC3 peptide vaccination (intradermal injections on days 1, 15, and 29 with dose escalation). The primary endpoint was the safety of GPC3 peptide vaccination. The secondary endpoints were immune response, as measured by IFN-γ ELISPOT assay, and the clinical outcomes tumor response, time to tumor progression, and overall survival (OS).
Results: GPC3 vaccination was well-tolerated. One patient showed a partial response, and 19 patients showed stable disease 2 months after initiation of treatment. Four of the 19 patients with stable disease had tumor necrosis or regression that did not meet the criteria for a partial response. Levels of the tumor markers α-fetoprotein and/or des-γ-carboxy prothrombin temporarily decreased in nine patients. The GPC3 peptide vaccine induced a GPC3-specific CTL response in 30 patients. Furthermore, GPC3-specific CTL frequency after vaccination correlated with OS. OS was significantly longer in patients with high GPC3-specific CTL frequencies (N = 15) than in those with low frequencies (N = 18; P = 0.033).
Conclusions: GPC3-derived peptide vaccination was well-tolerated, and measurable immune responses and antitumor efficacy were noted. This is the first study to show that peptide-specific CTL frequency can be a predictive marker of OS in patients with HCC receiving peptide vaccination. Clin Cancer Res; 18(13); 3686–96. ©2012 AACR.
Evidence for Efficacy of New Hsp90 Inhibitors Revealed by Ex Vivo Culture of Human Prostate Tumors
Authors: Centenera Margaret M. , Gillis Joanna L. , Hanson Adrienne R. , Jindal Shalini , Taylor Renea A. , Risbridger Gail P. , Sutherland Peter D. , Scher Howard I. , Raj Ganesh V. , Knudsen Karen E. , Yeadon Trina ,   for the Australian Prostate Cancer BioResource, Tilley Wayne D. , Butler Lisa M. 
Published: May 2012

Abstract
Purpose: Targeting Hsp90 has significant potential as a treatment for prostate cancer, but prototypical agents such as 17-allylamino-17 demethoxygeldanamycin (17-AAG) have been ineffective in clinical trials. Recently, a phase I study aimed at defining a biologically active dose reported the first response to an Hsp90 inhibitor in a patient with prostate cancer, which supports the development of new generation compounds for this disease.
Experimental Design: The biological actions of two new synthetic Hsp90 inhibitors, NVP-AUY922 and NVP-HSP990, were evaluated in the prostate cancer cell lines PC-3, LNCaP, and VCaP and in an ex vivo culture model of human prostate cancer.
Results: In cell lines, both NVP-AUY922 and NVP-HSP990 showed greater potency than 17-AAG with regard to modulation of Hsp90 client proteins, inhibition of proliferation, and induction of apoptotic cell death. In prostate tumors obtained from radical prostatectomy that were cultured ex vivo, treatment with 500 nmol/L of NVP-AUY922, NVP-HSP990, or 17-AAG caused equivalent target modulation, determined by the pharmacodynamic marker Hsp70, but only NVP-AUY922 and NVP-HSP990 showed antiproliferative and proapoptotic activity.
Conclusions: This study provides some of the first evidence that new generation Hsp90 inhibitors are capable of achieving biologic responses in human prostate tumors, with both NVP-AUY922 and NVP-HSP990 showing potent on-target efficacy. Importantly, the ex vivo culture technique has provided information on Hsp90 inhibitor action not previously observed in cell lines or animal models. This approach, therefore, has the potential to enable more rational selection of therapeutic agents and biomarkers of response for clinical trials. Clin Cancer Res; 18(13); 3562–70. ©2012 AACR.
New Directions for Biologic Targets in Urothelial Carcinoma
Authors: Richter Suzanne , Sridhar Srikala S. 
Published: May 2012

Abstract
Urothelial carcinoma remains an important oncologic problem with significant morbidity and mortality. This article provides an overview of the current status of treatment of urothelial carcinoma, with an update on current trials and recent American Society of Clinical Oncology abstracts. As an alternative to focusing on the metastatic setting, we take a broad look at drug development to date, as it spans from early disease to advanced disease in the context of emerging molecular data. This approach allows us to show that each stage involves key considerations based on emerging evidence regarding molecular biology, stage-specific novel endpoints, and rational patient selection that may help further trial designs in the future. Key issues, such as neoadjuvant versus adjuvant perioperative chemotherapy, approaches to salvage second-line therapy in the metastatic setting, and treatment of elderly and cisplatin-ineligible patients, are discussed. New paradigms in clinical research, including novel endpoints, upfront rational patient selection, biomarkers, and trial design, are also addressed. Mol Cancer Ther; 11(6); 1226–35. ©2012 AACR.
Beta-Testing of PI3-Kinase Inhibitors: Is Beta Better?
Authors: Shepherd Peter R. , Denny William A. 
Published: May 2012

Abstract
Although it has been known for some time that PTEN-null tumors require expression of the p110β isoform of phosphoinositide 3-kinase for growth, the corollary demonstration that small-molecule inhibitors of p110β are effective drugs for such tumors has not been shown. This has now been rectified by the demonstration that the TGX221 analogue KIN-193 is effective in mouse xenografts of HCC70 and PC3 human tumor cell lines. Cancer Discov; 2(5); 393–4. ©2012 AACR.
Commentary on Ni et al., p. 425.
Multisite Randomized Trial of a Single-Session Versus Multisession Literacy-Sensitive Self-Care Intervention for Patients With Heart Failure
Authors: DeWalt Darren A. , Schillinger Dean , Ruo Bernice , Bibbins-Domingo Kirsten , Baker David W. , Holmes George M. , Weinberger Morris , Macabasco-O'Connell Aurelia , Broucksou Kimberly , Hawk Victoria , Grady Kathleen L. , Erman Brian , Sueta Carla A. , Chang Patricia P. , Cene Crystal Wiley , Wu Jia-Rong , Jones Christine D. , Pignone Michael 
Published: May 2012

Background—
Self-care training can reduce hospitalization for heart failure (HF), and more intensive intervention may benefit more vulnerable patients, including those with low literacy.

Methods and Results—

A 1-year, multisite, randomized, controlled comparative effectiveness trial with 605 patients with HF was conducted. Those randomized to a single session received a 40-minute in-person, literacy-sensitive training; the multisession group received the same initial training and then ongoing telephone-based support. The primary outcome was combined incidence of all-cause hospitalization or death; secondary outcomes included HF-related hospitalization and HF-related quality of life, with prespecified stratification by literacy. Overall, the incidence of all-cause hospitalization and death did not differ between intervention groups (incidence rate ratio, 1.01; 95% confidence interval, 0.83–1.22). The effect of multisession training compared with single-session training differed by literacy group: Among those with low literacy, the multisession training yielded a lower incidence of all-cause hospitalization and death (incidence rate ratio, 0.75; 95% confidence interval, 0.45–1.25), and among those with higher literacy, the multisession intervention yielded a higher incidence (incidence rate ratio, 1.22; 95% confidence interval, 0.99–1.50; interaction
P
=0.048). For HF-related hospitalization, among those with low literacy, multisession training yielded a lower incidence (incidence rate ratio, 0.53; 95% confidence interval, 0.25–1.12), and among those with higher literacy, it yielded a higher incidence (incidence rate ratio, 1.32; 95% confidence interval, 0.92–1.88; interaction
P
=0.005). HF-related quality of life improved more for patients receiving multisession than for those receiving single-session interventions at 1 and 6 months, but the difference at 12 months was smaller. Effects on HF-related quality of life did not differ by literacy.

Conclusions—
Overall, an intensive multisession intervention did not change clinical outcomes compared with a single-session intervention. People with low literacy appear to benefit more from multisession interventions than people with higher literacy.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00378950.
Prevalence and Prognostic Significance of T-Wave Inversions in Right Precordial Leads of a 12-Lead Electrocardiogram in the Middle-Aged Subjects
Authors: Aro Aapo L. , Anttonen Olli , Tikkanen Jani T. , Junttila M. Juhani , Kerola Tuomas , Rissanen Harri A. , Reunanen Antti , Huikuri Heikki V. 
Published: May 2012

Background—

T-wave inversion in right precordial leads V
1
to V
3
is a relatively common finding in a 12-lead ECG of children and adolescents and is infrequently found also in healthy adults. However, this ECG pattern can also be the first presentation of arrhythmogenic right ventricular cardiomyopathy. The prevalence and prognostic significance of T-wave inversions in the middle-aged general population are not well known.

Methods and Results—

We evaluated 12-lead ECGs of 10 899 Finnish middle-aged subjects (52% men, mean age 44±8.5 years) recorded between 1966 and 1972 for the presence of inverted T waves and followed the subjects for 30±11 years. Primary end points were all-cause mortality, cardiac mortality, and arrhythmic death. T-wave inversions in right precordial leads V
1
to V
3
were present in 54 (0.5%) of the subjects. In addition, 76 (0.7%) of the subjects had inverted T waves present only in leads other than V
1
to V
3
. Right precordial T-wave inversions did not predict increased mortality (not significant for all end points). However, inverted T waves in leads other than V
1
to V
3
were associated with an increased risk of cardiac and arrhythmic death (
P
<0.001 for both).

Conclusions—
T-wave inversions in right precordial leads are relatively rare in the general population, and are not associated with adverse outcome. Increased mortality risk associated with inverted T waves in other leads may reflect the presence of an underlying structural heart disease.
Space–Time Extremes in Short-Crested Storm Seas
Authors: Fedele Francesco 
Published: May 2012

AbstractThis study develops a stochastic approach to model short-crested stormy seas as random fields both in space and time. Defining a space–time extreme as the largest surface displacement over a given sea surface area during a storm, associated statistical properties are derived by means of the theory of Euler characteristics of random excursion sets in combination with the Equivalent Power Storm model. As a result, an analytical solution for the return period of space–time extremes is given. Subsequently, the relative validity of the new model and its predictions are explored by analyzing wave data retrieved from NOAA buoy 42003, located in the eastern part of the Gulf of Mexico, offshore Naples, Florida. The results indicate that, as the storm area increases under short-crested wave conditions, space–time extremes noticeably exceed the significant wave height of the most probable sea state in which they likely occur and that they also do not violate Stokes–Miche-type upper limits on wave heights.
Application and evaluation of biomechanical models and scores for the planning of total hip arthroplasty
Authors: Eschweiler Jörg , Fieten Lorenz , Dell’Anna Jasmin , Kabir Koroush , Gravius Sascha , Tingart Markus , Radermacher Klaus 
Published: May 2012

Intimate knowledge of the biomechanics of a given individual hip joint provides a potential advantage during the planning of total hip arthroplasty, and would thus have a positive influence over the outcome of such an intervention. In current clinical practise, the surgical planning is based solely on the status of the individual hip and its radiographic appearance. However, additional information could be gathered from the radiography to be used as input data for biomechanical models aimed at calculating the resultant force FR within the hip joint. An investigation of the biomechanical models by Pauwels, Debrunner and Iglič was performed, where the magnitude of FR calculated by the models showed a favourable comparison to the in-vivo data from instrumented prostheses by Bergmann. The Blumentritt model returned abnormally high results. The computational results showed large variations for FR orientation, which tends to depend more on the model used than on patient-specific parameters. Furthermore, a discrepancy was found between the data gathered from instrumented prostheses and the Standing Human Model within the ‘AnyBody Modeling System™’ software by AnyBody Tech. Additionally, the variations in inter-rater and intra-rater errors made while localizing radiographic landmarks were analysed with respect to their influence on Babisch-Layher-Blumentritt (BLB)-scoring using the Blumentritt hip model.