bluuebunny/crossref_metadata_2025 huggingface dataset:
Individualized therapy for metastatic colorectal cancer
Authors: Silvestri A. , Pin E. , Huijbers A. , Pellicani R. , Parasido E. M. , Pierobon M. , Petricoin E. , Liotta L. , Belluco C.
Published: April 2013

Systemic therapeutic efficacy is central to determining the outcome of patients with metastatic colorectal cancer (CRC). In these patients, there is a critical need for predictive biomarkers to optimize efficacy whilst minimizing toxicity. The integration of a new generation of molecularly targeted drugs into the treatment of CRC, coupled with the development of sophisticated technologies for individual tumours as well as patient molecular profiling, underlines the potential for personalized medicine. In this review, we focus on the latest progress made within the genomic and proteomic fields, concerning predictive biomarkers for individualized therapy in metastatic CRC.
Impact of oral silymarin on virus‐ and non‐virus‐specific T‐cell responses in chronic hepatitis C infection
Authors: Adeyemo O. , Doi H. , Rajender Reddy K. , Kaplan D. E.
Published: April 2013

Silymarin displays anti‐inflammatory effects on T lymphocytes in vitro. The immunomodulatory properties of oral silymarin in vivo in humans with chronic hepatitis C have not previously been characterized. We hypothesized that silymarin would suppress T‐cell proliferation and pro‐inflammatory cytokine production of virus‐ and non‐virus‐specific T cells while increasing anti‐inflammatory IL‐10 production in vivo. Patients from one site of the SyNCH‐HCV double‐masked, placebo‐controlled study of oral silymarin in prior interferon nonresponders with chronic hepatitis C provided blood samples at baseline and treatment week 20. Mononuclear cells were stimulated with recombinant HCV proteins and controls in 3H‐thymidine proliferation assays, IFNγ ELISPOT and IL‐10 ELISPOT. The frequency of CD4+CD25hi and CD4+foxp3+ regulatory T cells, serum cytokine levels, serum IP‐10 and lymphocyte interferon‐stimulated gene expression were also quantified at baseline and week 20. Thirty‐two patients were recruited (10; placebo, 11; 420 mg three times a day, 11; 700 mg three times a day). Serum ALT and HCV RNA titres did not change in any group. HCV‐specific CD4+ T‐cell proliferation and the frequency of IFNγ‐ and IL‐10‐producing T cells were not significantly changed in silymarin‐treated subjects. However, C. albicans‐induced T‐cell IFNγ and phytohaemagglutinin‐induced T‐cell proliferation were suppressed by silymarin therapy. A trend towards augmentation of interferon‐induced ISG15 expression was present in the high‐dose silymarin group. While no effect on HCV‐specific T cells was identified, these data confirm that high‐dose oral silymarin exerts modest nonspecific immunomodulatory effects in vivo. The impact of this anti‐inflammatory effect on long‐term liver health in chronic hepatitis C merits future clinical investigation.
Does Economic Freedom Foster Tolerance?
Authors: Berggren Niclas , Nilsson Therese
Published: April 2013

Tolerance has the potential to affect both economic growth and wellbeing. It is therefore important to discern its determinants. We contribute to the literature by investigating whether the degree to which economic institutions and policies are market‐oriented is related to different measures of tolerance. Cross‐sectional and first‐difference regression analysis of up to 69 countries reveals that economic freedom is positively related to tolerance towards homosexuals, especially in the longer run, while tolerance towards people of a different race and a willingness to teach kids tolerance are not strongly affected by how free markets are. Stable monetary policy and outcomes is the area of economic freedom most consistently associated with greater tolerance, but the quality of the legal system seems to matter as well. Through instrumental variables and first‐difference results we find indications of a causal relationship.
Multidimensional Responsiveness: The Determinants of Legislators' Representational Priorities
Authors: Harden Jeffrey J.
Published: April 2013

American politics scholars typically conceptualize representation narrowly as mass‐elite policy responsiveness, with many studies identifying factors that hinder that relationship. These findings contrast with the high reelection rates in American legislatures. I show that policy is only one of several dimensions through which legislators provide representation. I unify policy, service, allocation, and descriptive representation in a model of legislators' priorities and then test it with survey experiments administered to 1,175 state legislators. I posit that legislators systematically emphasize different dimensions to further the goal of reelection. Results show that legislative institutions, district demand, and individual traits structure legislators' strategic representational priorities.
Complete Group Classifications and Symmetry Reductions of the Fractional Fifth‐Order KdV Types of Equations
Authors: Liu Hanze
Published: April 2013

This paper is concerned with the fractional fifth‐order KdV types of equations, the complete group classification is performed on the general fractional fifth‐order partial differential equation (FPDE), which includes a lot of important fifth‐order fractional differential equations and nonlinear evolution equations (NLEEs) as its special cases. In particular, all of the point symmetries of the fifth‐order nonlinear evolution equation are presented with respect to the arbitrary parameters of the equation. In the sense of point symmetry, all of the vector fields of the equations are obtained. Then, the symmetry reductions are provided, and the exact analytic solutions to the general fifth‐order KdV equations are investigated.
Interaction of Mycobacterium tuberculosis Cell Wall Components with the Human Natural Killer Cell Receptors NKp44 and Toll‐Like Receptor 2
Authors: Esin S. , Counoupas C. , Aulicino A. , Brancatisano F. L. , Maisetta G. , Bottai D. , Di Luca M. , Florio W. , Campa M. , Batoni G.
Published: April 2013

We have previously demonstrated that a soluble form of the human NK cell natural cytotoxicity receptor NKp44, binds to the surface of Mycobacterium tuberculosis (MTB). Herein, we investigated the interaction of MTB cell wall components (CWC) with NKp44 or with Toll‐like receptor 2 (TLR2) and the role of NKp44 and TLR2 in the direct activation of NK cells upon stimulation with MTB CWC. By using several purified bacterial CWC in an ELISA, we demonstrated that NKp44 was able to bind to the MTB cell wall core mycolyl‐arabinogalactan‐peptidoglycan (mAGP) as well as to mycolic acids (MA) and arabinogalactan (AG), while soluble TLR2 bound to MTB peptidoglycan (PG), but not to MA or AG. The mAGP complex induced NK cell expression of CD25, CD69, NKp44 and IFN‐γ production at levels comparable to M. bovis Bacillus Calmette–Guérin‐stimulated (BCG) cells. While AG and MA used alone failed to induce NK cell activation, mycobacterial PG‐exhibited NK cell stimulatory capacity. Activation of resting NK cells by mAGP and IFN‐γ production were inhibited by anti‐TLR2 MAb, but not by anti‐NKp44 MAb. Differently, anti‐NKp44 MAb partially inhibited CD69 expression on NK cells pre‐activated with IL‐2 and then stimulated with mAGP or whole BCG. Overall, these results provide evidence that components abundant in mycobacterial cell wall are able to interact with NKp44 (AG, MA) and TLR‐2 (PG), respectively. While interaction of TLR2 with mycobacterial cell wall promotes activation of resting NK cells and IFN‐γ production, NKp44 interaction with its putative ligands could play a secondary role in maintaining cell activation.
Levels of Interleukin‐(IL)‐12p40 are Markedly Increased in Brucellosis Among Patients with Specific IL‐12B Genotypes
Authors: Eskandari‐Nasab E. , Moghadampour M. , Asadi‐Saghandi A. , Kharazi‐nejad E. , Rezaeifar A. , Pourmasoumi H.
Published: April 2013

Brucellosis remains a major zoonosis worldwide. Brucella antigens induce the production of T‐helper 1 (Th1) cytokines such as interleukin‐12 (IL‐12) in humans. We aimed to investigate the association of two single nucleotide polymorphisms (SNPs) in the gene encoding the IL‐12p40 cytokine (IL‐12B) with brucellosis and to examine the functionality of these SNPs through measuring serum levels of IL‐12p40. We genotyped IL‐12B gene rs3212227, A>C; rs6887695 G>C polymorphisms in a case‐control study on a total of 281 subjects including 153 patients with active brucellosis and 128 healthy controls, using RFLP and serum IL‐12p40 levels, were assessed by ELISA. The rs3212227 minor allele (C) and homozygote genotype (CC) were more frequent in controls compared with patients with brucellosis (P = 0.006, OR = 0.608, 95%CI = 0.429–0.861 for the C allele; P = 0.024, OR = 0.443, 95% CI: 0.218–0.900 for the CC genotype). Comparison of IL‐12B genotypes and serum levels of the IL‐12p40 revealed that rs3212227 AA genotype, with higher frequency in patients than in controls, was associated with increased levels of the cytokine (P = 0.0001). Furthermore, the distribution of haplotype and genotype combinations in our study suggested that rs3212227C/rs6887695C haplotype or CC/GC or CC/CC genotype combinations may protect controls against Brucella infection by contributing to a functional downregulation of the serum IL‐12p40 production in vivo, as shown by ELISA (P < 0.05). Overall, our study demonstrated that rs3212227 A variant was associated with higher levels of serum IL‐12p40 and could possibly contribute to an inherited predisposition to brucellosis.
Molecular phylogeny of the beetle tribe Oxypodini (Coleoptera: Staphylinidae: Aleocharinae)
Authors: OSSWALD JUDITH , BACHMANN LUTZ , GUSAROV VLADIMIR I.
Published: April 2013

This is the first study to comprehensively address the phylogeny of the tribe Oxypodini Thomson and its phylogenetic relationships to other tribes within the staphylinid subfamily Aleocharinae. Using the hitherto largest molecular dataset of Aleocharinae comprising of 4599 bp for representatives of 22 tribes, the Oxypodini are recovered as non‐monophyletic. Members of the tribe belong to three distantly related lineages within the Aleocharinae: (i) the Amarochara group as sister clade to the tribe Aleocharini, (ii) the subtribe Tachyusina within a clade that also includes the tribes Athetini and Hygronomini, (iii) all other Oxypodini in a clade that also includes the tribes Placusini, Hoplandriini and Liparocephalini. Based on the inferred phylogeny, five subtribes of the Oxypodini are recognized: Dinardina Mulsant & Rey, Meoticina Seevers, Microglottina Fenyes, Oxypodina Thomson and Phloeoporina Thomson. The following changes in the classification of the Aleocharinae are proposed: (i) Amarochara Thomson is removed from the Oxypodini and placed in the tribe Aleocharini; (ii) the subtribe Taxicerina Lohse of the Athetini is reinstated as tribe Taxicerini to include Discerota Mulsant & Rey, Halobrecta Thomson (both removed from the Oxypodini) and Taxicera Mulsant & Rey; (iii) the subtribe Tachyusina Thomson is excluded from the Oxypodini and provisionally treated as tribe Tachyusini; (iv) the oxypodine subtribe name Blepharhymenina Klimaszewski & Peck is placed in synonymy with the subtribe name Dinardina Mulsant & Rey.
Discovery of the natural anti‐Gal antibody and its past and future relevance to medicine
Authors: Galili Uri
Published: April 2013

This is a personal account of the discovery of the natural anti‐Gal antibody, the most abundant natural antibody in humans, the reciprocal distribution of this antibody and its ligand the α‐gal epitope in mammals and the immunological barrier this antibody has formed in porcine to human xenotransplantation. This barrier has been overcome in the recent decade with the generation of α1,3‐galactosyltransferase gene‐knockout pigs. However, anti‐Gal continues to be relevant in medicine as it can be harnessed for various therapeutic effects. Anti‐Gal converts tumor lesions injected with α‐gal glycolipids into vaccines that elicit a protective anti‐tumor immune response by in situ targeting of tumor cells for uptake by antigen‐presenting cells. This antibody further accelerates wound and burn healing by interaction with α‐gal nanoparticles applied to injured areas and induction of rapid recruitment and activation of macrophages. Anti‐Gal/α‐gal nanoparticle immune complexes may further induce rapid recruitment and activation of macrophages in ischemic myocardium and injured nerves, thereby inducing tissue regeneration and prevention of fibrosis.
Design of a Large Range XY Nanopositioning System
Authors: Awtar Shorya , Parmar Gaurav
Published: April 2013

Achieving large motion range (>1 mm) along with nanometric motion quality (<10 nm) simultaneously has been a key challenge in nanopositioning systems. Practical limitations associated with the individual physical components (bearing, actuators, and sensors) and their integration, particularly in the case of multi-axis systems, have restricted the range of currently available nanopositioning systems to approximately 100 μm per axis. This paper presents a novel physical system layout, comprising a bearing, actuators, and sensors, that enables large range XY nanopositioning. The bearing is based on a parallel-kinematic XY flexure mechanism that provides a high degree of geometric decoupling between the two motion axes by avoiding geometric over-constraint, provides actuator isolation that allows the use of large-stroke single-axis actuators, and enables a complementary end-point sensing scheme using commonly available sensors. These attributes help achieve 10 mm × 10 mm motion range in the proposed nanopositioning system. Having overcome the physical system design challenges, a dynamic model of the proposed nanopositioning system is created and verified via system identification. In particular, dynamic nonlinearities associated with the large displacements of the flexure mechanism and resulting controls challenges are identified. The physical system is fabricated, assembled, and tested to validate its simultaneous large range and nanometric motion capabilities. Preliminary closed-loop test results, which highlight the potential as well as pending challenges associated with this new design configuration, are presented.
Ciprofloxacin-associated posterior reversible encephalopathy
Authors: Al Bu Ali Waleed Hammad
Published: April 2013

Posterior reversible encephalopathy syndrome (PRES) is a clinico-neuroradiological syndrome characterised by numerous symptoms and of no specific aetiology. Headache, confusion, seizures, cortical visual disturbances or blindness are the key symptoms. As this syndrome is reversible and readily treated by interrupting or discontinuing the aetiology, it should sharply be acknowledged. Ciprofloxacin was associated with PRES in an adolescent male treated from chest infection. It was managed in a hospital intensive care unit and was observed until disappearance.
Patient-reported outcomes of cancer survivors in England 1–5 years after diagnosis: a cross-sectional survey
Authors: Glaser Adam W , Fraser Lorna K , Corner Jessica , Feltbower Richard , Morris Eva J A , Hartwell Greg , Richards Mike
Published: April 2013

Objectives

To determine the feasibility of collecting population-based patient-reported outcome measures (PROMs) in assessing quality of life (QoL) to inform the development of a national PROMs programme for cancer and to begin to describe outcomes in a UK cohort of survivors.

Design

Cross-sectional postal survey of cancer survivors using a population-based sampling approach.

Setting

English National Health Service.

Participants

4992 breast, colorectal, prostate and non-Hodgkin's lymphoma (NHL) survivors 1–5 years from diagnosis.

Primary and secondary outcome measures

Implementation issues, response rates, cancer-specific morbidities utilising items including the EQ5D, tumour-specific subscales of the Functional Assessment of Cancer Therapy and Social Difficulties Inventory.

Results

3300 (66%) survivors returned completed questionnaires. The majority aged 85+ years did not respond and the response rates were lower for those from more deprived area. Response rates did not differ by gender, time since diagnosis or cancer type. The presence of one or more long-term conditions was associated with significantly lower QoL scores. Individuals from most deprived areas reported lower QoL scores and poorer outcomes on other measures, as did those self-reporting recurrent disease or uncertainty about disease status. QoL scores were comparable at all time points for all cancers except NHL. QoL scores were lower than those from the general population in Health Survey for England (2008) and General Practice Patient Survey (2012). 47% of patients reported fear of recurrence, while 20% reported moderate or severe difficulties with mobility or usual activities. Bowel and urinary problems were common among colorectal and prostate patients. Poor bowel and bladder control were significantly associated with lower QoL.

Conclusions

This method of assessing QoL of cancer survivors is feasible and acceptable to most survivors. Routine collection of national population-based PROMs will enable the identification of, and the support for, the specific needs of survivors while allowing for comparison of outcome by service provider.
The new oral anticoagulants: practical management for patients attending for endoscopic procedures
Authors: Woodhouse C , Evans G , Muller A F
Published: April 2013

Guidelines published by the British Society of Gastroenterology have standardised the care of patients attending for endoscopy procedures, taking aspirin, clopidogrel and warfarin.

Two new oral anticoagulant drugs, Rivaroxaban and Dabigatran, are licensed and National Institute of Clinical Excellence (NICE) approved for use in the UK. Unlike warfarin, these drugs do not require regular monitoring, and are at least as effective in preventing stroke in non-valvular atrial fibrillation. As such, they are likely to become popular among patients and clinicians alike. This paper summarises the practical management of patients taking these drugs attending for endoscopic procedures.
Overexpression of a moso bamboo (Phyllostachys edulis) transcription factor gene PheWRKY1 enhances disease resistance in transgenic Arabidopsis thaliana
Authors: Cui Xiao-Wei , Zhang Ying , Qi Fei-Yan , Gao Jian , Chen Yuan-Wen , Zhang Chun-Ling
Published: April 2013

Members of plant WRKY transcription factor families are implicated in defense responses and various other physiological processes. To study the function of WRKY transcription factors in moso bamboo (Phyllostachys edulis (Carrière) J. Houz.), a PheWRKY1 gene (GenBank accession number: GU944762) was cloned by reverse transcription polymerase chain reaction. An overexpression vector for this gene was constructed and transformed into Arabidopsis thaliana (L.) Heynh. by an agrobacterium-mediated method. To determine the effect of PheWRKY1 gene overexpression on disease resistance in A. thaliana, the photosynthetic parameters and the expression of pathogenesis-related (PR) genes were examined after Pseudomonas syringae PV Tomato DC3000 (Pst DC3000) infection. Compared to wild-type plants, most PheWRKY1-overexpressing plants did not exhibit spreading maceration to systemic leaves and had a better photosynthetic capacity after Pst DC3000 infection. Furthermore, PheWRKY1-overexpressing plants accumulated significantly more PR1, PR2, PR5, and nonexpressor of PR genes (NPR1) transcripts. These results demonstrated that transgenic Arabidopsis overexpressing PheWRKY1 gene exhibited improved resistance to bacterial infection.
MOTION ENERGY DISSIPATION IN TRAFFIC FLOW ON A CURVED ROAD
Authors: ZHU WEN-XING
Published: April 2013

We investigate the energy loss of vehicles running on a curved road. The energy dissipation model for traffic flow is derived. Simulations are carried out to examine the energy dissipation in traffic flow on a curved road with friction coefficient and radii of curvature. Results analysis show that the total energy dissipation increases with an increase in the friction coefficient and radii of curvature. Moreover, the energy dissipation rate varies with the density and road length, which is in good agreement with the real traffic situations.
UNIFICATION OF PR REGION FLOORPLANNING AND FINE-GRAINED PLACEMENT FOR DYNAMIC PARTIALLY RECONFIGURABLE FPGAS
Authors: HE RUINING , LIANG GUOQIANG , MA YUCHUN , WANG YU , BIAN JINIAN
Published: April 2013

Dynamic Partially Reconfiguration (DPR) designs provide additional benefits compared to traditional FPGA application. However, due to the lack of support from automatic design tools in current design flow, designers have to manually define the dimensions and positions of Partially Reconfigurable Regions (PR Regions). The following fine-grained placement for system modules is also limited because it takes the floorplanning result as a rigid region constraint. Therefore, the manual floorplanning is laborious and may lead to inferior fine-grained placement results. In this paper, we propose to integrate PR Region floorplanning with fine-grained placement to achieve the global optimization of the whole DPR system. Effective strategies for tuning PR Region floorplanning and apposite analytical evaluation models are customized for DPR designs to handle the co-optimization for both PR Regions and static region. Not only practical reconfiguration cost and specific reconfiguration constraints for DPR system are considered, but also the congestion estimation can be relaxed by our approach. Especially, we established a two-stage stochastic optimization framework which handles different objectives in different optimization stages so that automated floorplanning and global optimization can be achieved in reasonable time. Experimental results demonstrate that due to the flexibility benefit from the unification of PR Region floorplanning and fine-grained placement, our approach can improve 20.9% on critical path delay, 24% on reconfiguration delay, 12% on congestion, and 8.7% on wire length compared to current DPR design method.
A TWO-DIMENSIONAL HARDY TYPE INEQUALITY FOR FUZZY INTEGRALS
Authors: ROMÁN-FLORES H. , FLORES-FRANULIČ A. , CHALCO-CANO Y. , RALESCU DAN
Published: April 2013

In this paper, a two-dimensional Hardy type inequality for fuzzy integrals is proved. Also, some illustrative examples are presented.
Heme oxygenase-1 deficiency promotes the development of necrotizing enterocolitis-like intestinal injury in a newborn mouse model
Authors: Schulz Stephanie , Wong Ronald J. , Jang Kyu Yun , Kalish Flora , Chisholm Karen M. , Zhao Hui , Vreman Hendrik J. , Sylvester Karl G. , Stevenson David K.
Published: April 2013

Necrotizing enterocolitis (NEC) is typified by mucosal destruction, which subsequently can lead to intestinal necrosis. Prematurity, enteral feeding, and bacterial colonization are the main risk factors and, combined with other stressors, can cause increased intestinal permeability, injury, and an exaggerated inflammatory response. Heme oxygenase-1 (HO-1) mediates intestinal protection due to anti-inflammatory, antioxidative, and antiapoptotic effects of its products carbon monoxide, biliverdin, and bilirubin. This study investigates a possible role of HO-1 in the pathogenesis of NEC using a newborn mouse model. We induced NEC-like intestinal injury in 7-day-old HO-1 heterozygous (HO-1 Het, Hmox1+/-) and wild-type (Wt, Hmox1+/+) mice by gavage feeding and hypoxic exposures. Control (Con) pups of both genotypes were dam-fed. Intestines of HO-1 Het Con pups appeared predisposed to injury, with higher histological damage scores, more TUNEL-positive cells, and a significant reduction in muscularis externa thickness compared with Wt Con pups. The increase in HO activity after HO-1 induction by the substrate heme or by hypoxic stress was significantly impaired in HO-1 Het pups. After induction of intestinal injury, HO-1 Het pups displayed significantly higher NEC incidence (78 vs. 43%), mortality (83 vs. 54%), and median scores (2.5 vs. 1.5) than Wt NEC pups. PCR array analyses revealed increased expressions of IL-1β, P-selectin, matrix metallopeptidase 2, collagen type XVIII-α1, serpine 1, and others in NEC-induced HO-1 Het ileal and jejunal tissues. We conclude that a partial HO-1 deficiency promotes experimental NEC-like intestinal injury, possibly mediated by exaggerated inflammation and disruption in tissue repair.
Sympathetic network drive during water deprivation does not increase respiratory or cardiac rhythmic sympathetic nerve activity
Authors: Holbein Walter W. , Toney Glenn M.
Published: April 2013

Effects of water deprivation on rhythmic bursting of sympathetic nerve activity (SNA) were investigated in anesthetized, bilaterally vagotomized, euhydrated (control) and 48-h water-deprived (WD) rats ( n = 8/group). Control and WD rats had similar baseline values of mean arterial pressure, heart rate, end-tidal CO2, and central respiratory drive. Although integrated splanchnic SNA (sSNA) was greater in WD rats than controls ( P < 0.01), analysis of respiratory rhythmic bursting of sSNA revealed that inspiratory rhythmic burst amplitude was actually smaller ( P < 0.005) in WD rats (+68 ± 6%) than controls (+208 ± 20%), and amplitudes of the early expiratory (postinspiratory) trough and late expiratory burst of sSNA were not different between groups. Further analysis revealed that water deprivation had no effect on either the amplitude or periodicity of the cardiac rhythmic oscillation of sSNA. Collectively, these data indicate that the increase of sSNA produced by water deprivation is not attributable to either increased respiratory or cardiac rhythmic burst discharge. Thus the sympathetic network response to acute water deprivation appears to differ from that of chronic sympathoexcitation in neurogenic forms of arterial hypertension, where increased respiratory rhythmic bursting of SNA and baroreflex adaptations have been reported.
SRC Signaling Is Crucial in the Growth of Synovial Sarcoma Cells
Authors: Michels Sebastian , Trautmann Marcel , Sievers Elisabeth , Kindler Dagmar , Huss Sebastian , Renner Marcus , Friedrichs Nicolaus , Kirfel Jutta , Steiner Susanne , Endl Elmar , Wurst Peter , Heukamp Lukas , Penzel Roland , Larsson Olle , Kawai Akira , Tanaka Shinya , Sonobe Hiroshi , Schirmacher Peter , Mechtersheimer Gunhild , Wardelmann Eva , Büttner Reinhard , Hartmann Wolfgang
Published: April 2013

Synovial sarcoma is a soft-tissue malignancy characterized by a reciprocal t(X;18) translocation encoding a chimeric transcriptional modifier. Several receptor tyrosine kinases have been found activated in synovial sarcoma; however, no convincing therapeutic concept has emerged from these findings. On the basis of the results of phosphokinase screening arrays, we here investigate the functional and therapeutic relevance of the SRC kinase in synovial sarcoma. Immunohistochemistry of phosphorylated SRC and its regulators CSK and PTP1B (PTPN1) was conducted in 30 synovial sarcomas. Functional aspects of SRC, including dependence of SRC activation on the SS18/SSX fusion proteins, were analyzed in vitro. Eventually, synovial sarcoma xenografts were treated with the SRC inhibitor dasatinib in vivo. Activated phospho (p)-(Tyr416)-SRC was detected in the majority of tumors; dysregulation of CSK or PTP1B was excluded as the reason for the activation of the kinase. Expression of the SS18/SSX fusion proteins in T-REx-293 cells was associated with increased p-(Tyr416)-SRC levels, linked with an induction of the insulin-like growth factor pathway. Treatment of synovial sarcoma cells with dasatinib led to apoptosis and inhibition of cellular proliferation, associated with reduced phosphorylation of FAK (PTK2), STAT3, IGF-IR, and AKT. Concurrent exposure of cells to dasatinib and chemotherapeutic agents resulted in additive effects. Cellular migration and invasion were dependent on signals transmitted by SRC involving regulation of the Rho GTPases Rac and RhoA. Treatment of nude mice with SYO-1 xenografts with dasatinib significantly inhibited tumor growth in vivo. In summary, SRC is of crucial biologic importance and represents a promising therapeutic target in synovial sarcoma. Cancer Res; 73(8); 2518–28. ©2013 AACR.
Bevacizumab-Induced Normalization of Blood Vessels in Tumors Hampers Antibody Uptake
Authors: Arjaans Marlous , Oude Munnink Thijs H. , Oosting Sjoukje F. , Terwisscha van Scheltinga Anton G.T. , Gietema Jourik A. , Garbacik Erik T. , Timmer-Bosscha Hetty , Lub-de Hooge Marjolijn N. , Schröder Carolina P. , de Vries Elisabeth G.E.
Published: April 2013

In solid tumors, angiogenesis occurs in the setting of a defective vasculature and impaired lymphatic drainage that is associated with increased vascular permeability and enhanced tumor permeability. These universal aspects of the tumor microenvironment can have a marked influence on intratumoral drug delivery that may often be underappreciated. In this study, we investigated the effect of blood vessel normalization in tumors by the antiangiogenic drug bevacizumab on antibody uptake by tumors. In mouse xenograft models of human ovarian and esophageal cancer (SKOV-3 and OE19), we evaluated antibody uptake in tumors by positron emission tomographic imaging 24 and 144 hours after injection of 89Zr-trastuzumab (SKOV-3 and OE19), 89Zr-bevacizumab (SKOV-3), or 89Zr-IgG (SKOV-3) before or after treatment with bevacizumab. Intratumor distribution was assessed by fluorescence microscopy along with mean vessel density (MVD) and vessel normalization. Notably, bevacizumab treatment decreased tumor uptake and intratumoral accumulation compared with baseline in the tumor models relative to controls. Bevacizumab treatment also reduced MVD in tumors and increased vessel pericyte coverage. These findings are clinically important, suggesting caution in designing combinatorial trials with therapeutic antibodies due to a possible reduction in tumoral accumulation that may be caused by bevacizumab cotreatment. Cancer Res; 73(11); 3347–55. ©2013 AACR.
Incidence and Predictive Value of Proteinuria in Community-Acquired Pneumonia
Authors: Spoorenberg Simone M.C. , Meijvis Sabine C.A. , Navis Gerjan , Ruven Henk J. , Biesma Douwe H. , Grutters Jan C. , Bos Willem Jan W.
Published: April 2013

Background/Aims: The presence of baseline proteinuria predicts the outcome in patients with chronic kidney disease and in the general population, independent of renal function. However, the predictive value of proteinuria during an episode of acute illness has not been reported yet. Therefore, we investigated the incidence and predictive value of proteinuria in patients with community-acquired pneumonia. Methods: An analysis of prospectively collected data, obtained from patients >18 years of age, was performed. Patients were hospitalized with community-acquired pneumonia in two hospitals in the Netherlands and participated in two consecutive clinical trials. A total protein/creatinine (P/C) ratio was measured in a urine sample from the day of admission. Patients were categorized in quartiles of P/C ratio. Primary outcome was length of hospital stay. Results: 198/319 patients (62%) had a P/C ratio >23 mg/mmol creatinine. In multivariate analysis, proteinuria turned out to be an independent predictor for length of stay and admission to the intensive care unit. Conclusion: The incidence of proteinuria during pneumonia is high and proteinuria is an independent predictor for length of hospital stay and admission to the intensive care unit. Proteinuria is a cheap and easily accessible marker for outcome and might be used to assess the severity of pneumonia.
Effect of Belly Board with Bladder Compression Device on Small Bowel Displacement from the Radiotherapy Field for Rectal Cancer
Authors: Chung Yoonsun , Yoon Hong I. , Keum Ki C. , Kim Joo H. , Choi Won H. , Nam Ki C. , Koom Woong S.
Published: April 2013

Background: The aim of this study was to investigate the effect of a belly board (BB) with the addition of a bladder compression device (BCD) for small bowel (SB) displacement from the radiotherapy field for rectal cancer. Patients and Methods: Computed tomography (CT) scans of 38 rectal cancer patients positioned on a BB were analyzed and compared with CT scans from the same patients after the addition of a BCD. The BCD moves the inferior border of the BB from the pubic symphysis to the lumbosacral junction. The treated and irradiated volumes of the SB and bladder were compared. The irradiated volume ratio of SB to abdominopelvic cavity (APC) and that of bladder to APC were analyzed. Results: With the BCD, the treated and irradiated volumes of SB decreased significantly (49.1 ± 48.0 vs. 60.9 ± 50.9 cc, p = 0.006 and 207.5 ± 140.8 vs. 482.8 ± 214.2 cc, p < 0.001, respectively). The irradiated volume ratio of bladder to APC with the BCD increased considerably compared to that without the BCD (25.2 ± 11.5 vs. 18.7 ± 10.5%, p < 0.001), and the ratio of irradiated volume of SB to APC decreased significantly with the BCD (18.8 ± 12.4 vs. 31.8 ± 12.1%, p < 0.001). Conclusion: This study showed that the addition of a BCD to the BB could effectively provide further displacement of SB from the rectal cancer radiotherapy field.
Stress Management and Mind-Body Medicine: A Randomized Controlled Longitudinal Evaluation of Students' Health and Effects of a Behavioral Group Intervention at a Middle-Size German University (SM-MESH)
Authors: Esch Tobias , Sonntag Ulrike , Esch Sonja Maren , Thees Stefanie
Published: April 2013

Background: Student life can be stressful. Hence, we started a regular mind-body medical stress management program in 2006. By today, more than 500 students took part and evaluations showed significant results, especially with regard to a reduction of stress warning signals. For further analysis, we now decided to run a randomized controlled longitudinal trial. Methods: Participating students at Coburg University were randomized into an intervention (n = 24) or a waitlist control group (n = 19). The intervention group completed 3 sets (pre/post/follow-up) and the control group 2 sets (pre/post) of self-administered questionnaires. The questionnaires included: SF-12 Health Survey, Perceived Stress Scale (PSS), Sense of Coherence (SOC-L9), Visual Analogue Scale (VAS) concerning stress, and the Stress Warning Signs (SWS) scale. Randomly selected participants of the intervention group were also queried in qualitative interviews. The intervention consisted of an 8 week stress management group program (mind-body medical stress reduction - MBMSR). Follow-up measures were taken after 6 months. Results: Virtually, no drop-out occurred. Our study showed significant effects in the intervention group concerning SF-12 Mental Component Scale (p = 0.05), SF-12 Physical Component Scale (p = 0.001), VAS (in general, p = 0.001) and SWS (emotional reactions, p <0.001), underlined by qualitative results, which showed a higher quality of life. Conclusions: The effectiveness of an MBMSR program in a group of supposedly healthy students could be demonstrated. Findings suggest that stress management might be given importance at universities that care for the performance, the quality of life, and stress-health status of their students, acknowledging and accounting for the challenging circumstances of university life, as well as the specific needs of the modern student population.
Interdecadal Amplitude Modulation of El Niño–Southern Oscillation and Its Impact on Tropical Pacific Decadal Variability*
Authors: Ogata Tomomichi , Xie Shang-Ping , Wittenberg Andrew , Sun De-Zheng
Published: April 2013

The amplitude of El Niño–Southern Oscillation (ENSO) displays pronounced interdecadal modulations in observations. The mechanisms for the amplitude modulation are investigated using a 2000-yr preindustrial control integration from the Geophysical Fluid Dynamics Laboratory Climate Model, version 2.1 (GFDL CM2.1). ENSO amplitude modulation is highly correlated with the second empirical orthogonal function (EOF) mode of tropical Pacific decadal variability (TPDV), which features equatorial zonal dipoles in sea surface temperature (SST) and subsurface temperature along the thermocline. Experiments with an ocean general circulation model indicate that both interannual and decadal-scale wind variability are required to generate decadal-scale tropical Pacific temperature anomalies at the sea surface and along the thermocline. Even a purely interannual and sinusoidal wind forcing can produce substantial decadal-scale effects in the equatorial Pacific, with SST cooling in the west, subsurface warming along the thermocline, and enhanced upper-ocean stratification in the east. A mechanism is proposed by which residual effects of ENSO could serve to alter subsequent ENSO stability, possibly contributing to long-lasting epochs of extreme ENSO behavior via a coupled feedback with TPDV.
Physical Mechanisms Underlying Selected Adaptive Sampling Techniques for Tropical Cyclones
Authors: Hoover Brett T. , Velden Chris S. , Majumdar Sharanya J.
Published: April 2013

To efficiently and effectively prioritize resources, adaptive observations can be targeted by using some objective criteria to estimate the potential impact an initial condition perturbation (or analysis increment) in a specific region would have on the future forecast. Several objective targeting guidance techniques have been developed, including total-energy singular vectors (TESV), adjoint-derived sensitivity steering vectors (ADSSV), and the ensemble transform Kalman filter (ETKF), all of which were tested during the 2008 The Observing System Research and Predictability Experiment (THORPEX) Pacific Asian Regional Campaign (T-PARC) and the Office of Naval Research Tropical Cyclone Structure-2008 (TCS-08) field experiments. An intercomparison between these techniques is performed in order to find underlying physical mechanisms in the respective guidance products, based on four tropical cyclone (TC) cases from the T-PARC/TCS-08 field campaigns. It is found that the TESV energy norm and the ADSSV response function are largely indirect measures of the TC track divergence that can be produced by an initial condition perturbation, explaining the strong correlation between these products. The downstream targets routinely chosen by the ETKF guidance system are often not found in the TESV and ADSSV guidance products, and it is found that downstream perturbations can affect the steering of a TC through the development of a Rossby wave in the subtropics that modulates the strength of the nearby subtropical ridge. It is hypothesized that the ubiquitousness of these downstream targets in the ETKF is largely due to the existence of large uncertainties downstream of the TC that are not taken into consideration by either the TESV or ADSSV techniques.
Dynamics of a Simulated North American Monsoon Gulf Surge Event
Authors: Newman Andrew J. , Johnson Richard H.
Published: April 2013

Gulf surges are transient disturbances that propagate along the Gulf of California (GoC) from south to north, transporting cool moist air toward the deserts of northwest Mexico and the southwest United States during the North American monsoon. They have been shown to modulate precipitation and have been linked to severe weather and flooding in northern Mexico and the southwest United States. The general features and progression of surge events are well documented but their detailed dynamical evolution is still unclear. In this study, a convection-permitting simulation is performed over the core monsoon region for the 12–14 July 2004 gulf surge event and the dynamics of the simulated surge are examined. Initially, convection associated with the tropical easterly wave precursor to Tropical Cyclone Blas creates a disturbance in the southern GoC on early 12 July. This disturbance is a precursor to the gulf surge on 13 July and is a Kelvin shock (internal bore under the influence of rotation) that dissipates in the central GoC. The surge initiates from inflow from the mouth of the GoC along with convective outflow impinging on the southern GoC. Continued convective outflow along the GoC generates multiple gravity currents and internal bores while intensifying the simulated surge as it propagates up the GoC. As the core of the surge reaches the northern GoC, a Kelvin shock is again the best dynamical fit to the phenomenon. Substantial low-level cooling and moistening are associated with the modeled surge along the northern GoC as is observed.
Tropical Cyclogenesis in the Western North Pacific as Revealed by the 2008–09 YOTC Data*
Authors: Xu Yamei , Li Tim , Peng Melinda
Published: April 2013

The Year of Tropical Convection (YOTC) high-resolution global reanalysis dataset was analyzed to reveal precursor synoptic-scale disturbances related to tropical cyclone (TC) genesis in the western North Pacific (WNP) during the 2008–09 typhoon seasons. A time filtering is applied to the data to isolate synoptic (3–10 day), quasi-biweekly (10–20 day), and intraseasonal (20–90 day) time-scale components. The results show that four types of precursor synoptic disturbances associated with TC genesis can be identified in the YOTC data. They are 1) Rossby wave trains associated with preexisting TC energy dispersion (TCED) (24%), 2) synoptic wave trains (SWTs) unrelated to TCED (32%), 3) easterly waves (EWs) (16%), and 4) a combination of either TCED-EW or SWT-EW (24%). The percentage of identifiable genesis events is higher than has been found in previous analyses.

Most of the genesis events occurred when atmospheric quasi-biweekly and intraseasonal oscillations are in an active phase, suggesting a large-scale control of low-frequency oscillations on TC formation in the WNP. For genesis events associated with SWT and EW, maximum vorticity was confined in the lower troposphere. During the formation of Jangmi (2008), maximum Rossby wave energy dispersion appeared in the middle troposphere. This differs from other TCED cases in which energy dispersion is strongest at low level. As a result, the midlevel vortex from Rossby wave energy dispersion grew faster during the initial development stage of Jangmi.
Fatigue failure of printed circuit board chemically etched copper traces in multifunctional composite structures
Authors: Kim Hyonny , González Miguel
Published: April 2013

One class of multifunctional composite structures is one that is capable of load-bearing while transferring electrical current across a given span. An example is large antenna systems integrated into composite skins of aircraft and spacecraft. Current aircraft missions that require large amounts of sensing equipment can potentially involve heavy and bulky wiring systems. The bulk and mass inefficiency of these systems can be avoided by using multifunctional structures that mimic printed circuit boards to carry both load and electrical current for power or data. The fatigue life and failure modes of these types of systems were experimentally investigated to understand the capability of embedded metals inside composite host materials. ‘Dog bone’ specimens with copper traces were used to measure the fatigue life as a function of loading level. The specimens were fabricated by mass-production printed circuit board methods using woven glass/epoxy composite and chemically etched copper traces that were embedded or surface mounted. Functional failure, described as failure of the copper trace while still maintaining load-bearing capability, was of primary interest. This occurred when the specimen was loaded at levels below 55% of static ultimate tensile strength. Fracture of the copper was caused by cracks forming in the composite surface and propagated through the copper trace. Completely embedded copper traces exhibited longer life than traces that were surface mounted on the composite. An elasto-plastic analysis and summary of experimental results in the form of copper strain amplitude allow results to be applicable to other configurations, i.e., host structures of different stiffness than woven glass/epoxy.
Dry friction and wear behavior of in-situ Al/Al3Ti composite
Authors: Habibolahzadeh A , Hassani A , Bagherpour E , Taheri M
Published: April 2013

Effects of different volume fractions of reinforcement and various loads applied in wear testing on dry tribological behavior of Al-Al3Ti in-situ composite were investigated. Mixture of aluminum and different amount of titanium powders has been compacted and combustion synthesized to obtain Al-Al3Ti composite with different percent of reinforcements. The results of pin-on-disk wear tests indicated that addition of Al3Ti to aluminum matrix increase wear resistance of the composite samples by 4 times compared to that of pure aluminum. In addition, presence of Al3Ti reinforcement reduced friction coefficient of the composites. Oxidation/abrasive mechanism was revealed to be dominant on wear behavior of Al-Al3Ti composites; adhesive wear decreased as volume fraction of the intermetallic increased in the composites.
Expressing Death Risk as Condensed Life Experience and Death Intensity
Authors: Ioannidis John P. A.
Published: April 2013

Some risk exposures, including many medical and surgical procedures, typically carry hazards of death that are difficult to convey and appreciate in absolute terms. I propose presenting the death risk as a condensed life experience (i.e., the equivalent amount of life T that would carry the same cumulative mortality hazard for a person of the same age and sex based on life tables). For example, if the risk of death during an elective 1-hour procedure is 0.01%, and same-age and same-sex people have a 0.01% death risk over 1 month, one can inform the patient that “this procedure carries the same death risk as living 1 month of normal life.” Comparative standards from other risky activities or from a person with the same disease at the same stage and same predictive profile could also be used. A complementary metric that may be useful to consider is the death intensity. The death intensity λ is the hazard function that shows the fold-risk estimate of dying compared with the reference person. The death intensity can vary substantially for different phases of the event, operation, or procedure (e.g., intraoperative, early postoperative, late postoperative), and this variability may also be useful to convey. T will vary depending on the time window for which it is computed. I present examples for calculating T and λ using literature data on accidents, ascent to Mount Everest, and medical and surgical procedures.
Association Between Infantile Spasms and Nonaccidental Head Injury
Authors: Birca Ala , D’Anjou Guy , Carmant Lionel
Published: April 2013

Infantile spasms constitute a severe epileptic encephalopathy of infancy with poor long-term developmental outcome. Many diverse etiologies have been associated with infantile spasms, but the pathophysiological process is still not fully understood. We describe 2 cases of previously healthy 1- and 3-month-old infants who suffered a nonaccidental head injury with extensive cerebral lesions. Both presented with acute focal seizures rapidly controlled with phenobarbital. Nevertheless, they developed infantile spasms after a latency period of 3-4 months. Spasms were rapidly controlled with vigabatrin. Both children manifested with developmental delay, either exacerbated (case 1) or elicited (case 2) by infantile spasms. Our report highlights nonaccidental head injury as a risk factor for developing infantile spasms following a seizure-free latency period. A better understanding of the pathophysiology linking accidental brain trauma with infantile spasms could lead to more effective neuroprotective strategies. In the meantime, increased awareness and follow-up are warranted.