2,537 research outputs found
Underwriting and investment risks in the property-liability insurance industry: Evidence prior to the 9-11 event
Underwriting and investment are two important and related business activities of insurance companies. However, studies on the interrelation between underwriting and investment risks of Property-Liability (P-L) insurance companies are sparse in the literature. Using a sample of US P-L insurers, this article conducts an empirical investigation of how these two risks are associated with each other in the 1994-2000 period (before the September 11th terrorist attack in 2001). Our results, robust to various estimations, suggest that there is no significant relationship between the underwriting and investment risks among our sample firms. Such results based on pre 9-11 event period provide some support for the conjecture of Achleitner et al. (Geneva Pap Risk Insur Issues Pract 27:275-282, 2002) that many insurance companies may have failed to take an integrated approach to risk management. This resulted in a heavy loss due to dual exposures in both underwriting and investment in the 9-11 event. In the aftermath of the recent global financial crisis, risk taking and risk management of financial institutions have received more attention and increasing scrutiny. We believe the current paper provides some useful insights in this vein. © 2010 Springer Science+Business Media, LLC.postprin
Modeling pegylated liposomal doxorubicin-induced hand-foot syndrome and intestinal mucositis in zebrafish
[[abstract]]Pegylated liposomal doxorubicin (PLD) has been widely used to treat cancer. The adverse effects of PLD noted in clinical practice, especially hand-foot syndrome (HFS), are regarded as unique, and the management methods for them remain limited. This study was aimed at developing a feasible experimental model for translational medicine to solve this clinical issue by using skin fluorescent transgenic zebrafish. We established an optimal protocol for the administration of Lipo-Dox™, a PLD in current clinical use, to the Tg(k18:dsred) zebrafish line expressing red fluorescence in keratinocytes. We made use of bodyweight, survival rate, gross observation, flssuorescent microscopic assessment, and pathological examination of the zebrafish to assess this model. The consecutive administration protocol of PLD resulted in growth retardation of the zebrafish embryo and survival impairment, indicating establishment of a significant toxicity. We observed fin necrosis and keratinocyte dissociation phenotypes in the PLD-treated fish after consecutive administration. The skin toxicity induced by the Lipo-Dox injection was subsequently reversible, which might be compatible with a clinical course of skin recovery after discontinuation of Lipo-Dox administration. Furthermore, we found that the number of intestinal goblet cells, an important marker of intestinal inflammation, in the Lipo-Dox-injected zebrafish was markedly increased, accompanied by impaired mucosal integrity. The intestinal inflammation induced by Lipo-Dox resembled the intestinal mucositis the clinical patients suffered from after the administration of PLD. In conclusion, we established a zebrafish model for PLD-induced HFS. The intestinal mucositis simultaneously noted in the PLD-treated zebrafish validated the similarity of clinical courses after administration of PLD. This model is easily assessable, efficient, and worthy for use in developing a new therapeutic protocol for prevention or treatment of HFS as well as intestinal mucositis. Further clinical investigations to validate the correlation between human and zebrafish data are warranted.[[journaltype]]國外[[ispeerreviewed]]Y[[booktype]]電子版[[countrycodes]]GB
Nephroprotective role of resveratrol and ursolic acid in aristolochic acid intoxicated zebrafish
[[incitationindex]]SCI[[booktype]]電子
Integrative analysis of next generation sequencing for small non-coding RNAs and transcriptional regulation in Myelodysplastic Syndromes
Abstract. Background: Myelodysplastic Syndromes (MDSS) are pre-leukemic disorders with increasing incident rates worldwide, but very limited treatment options. Little is known about small regulatory RNAs and how they contribute to pathogenesis, progression and transcriptome changes in MDS. Methods. Patients' primary marrow cells were screened for short RNAs (RNA-seq) using next generation sequencing. Exon arrays from the same cells were used to profile gene expression and additional measures on 98 patients obtained. Integrative bioinformatics algorithms were proposed, and pathway and ontology analysis performed. Results: In low-grade MDS, observations implied extensive post-transcriptional regulation via microRNAs (miRNA) and the recently discovered Piwi interacting RNAs (piRNA). Large expression differences were found for MDS-associated and novel miRNAs, including 48 sequences matching to miRNA star (miRNA*) motifs. The detected species were predicted to regulate disease stage specific molecular functions and pathways, including apoptosis and response to DNA damage. In high-grade MDS, results suggested extensive post-translation editing via transfer RNAs (tRNAs), providing a potential link for reduced apoptosis, a hallmark for this disease stage. Bioinformatics analysis confirmed important regulatory roles for MDS linked miRNAs and TFs, and strengthened the biological significance of miRNA*. The "RNA polymerase II promoters" were identified as the tightest controlled biological function. We suggest their control by a miRNA dominated feedback loop, which might be linked to the dramatically different miRNA amounts seen between low and high-grade MDS. Discussion. The presented results provide novel findings that build a basis of further investigations of diagnostic biomarkers, targeted therapies and studies on MDS pathogenesis. © 2011 Beck et al; licensee BioMed Central Ltd
Yin and Yang: CCN3 inhibits the pro-fibrotic effects of CCN2
Fibrotic disease is a significant cause of mortality. CCN2 (connective tissue growth factor [CTGF]), a member of the CCN family of matricellular proteins, plays a significant role in driving the fibrogenic effects of cytokines such as transforming growth factor β (TGFβ). It has been proposed that other members of the CCN family can either promote or antagonize the action of CCN2, depending on the context. A recent elegant study published by Bruce Riser and colleagues (Am J Pathol. 174:1725–34, 2009) illustrates that CCN3 (nov) antagonizes the fibrogenic effects of CCN2. This paper, the subject of this commentary, raises the intriguing possibility that CCN3 may be used as a novel anti-fibrotic therapy
Innate immune responses and antioxidant/oxidant imbalance are major determinants of human Chagas disease.
We investigated the pathological and diagnostic role of selected markers of inflammation, oxidant/antioxidant status, and cellular injury in human Chagas disease. METHODS: Seropositive/chagasic subjects characterized as clinically-symptomatic or clinically-asymptomatic (n = 116), seronegative/cardiac subjects (n = 102), and seronegative/healthy subjects (n = 45) were analyzed for peripheral blood biomarkers. RESULTS: Seropositive/chagasic subjects exhibited an increase in sera or plasma levels of myeloperoxidase (MPO, 2.8-fold), advanced oxidation protein products (AOPP, 56%), nitrite (5.7-fold), lipid peroxides (LPO, 12-17-fold) and malondialdehyde (MDA, 4-6-fold); and a decline in superoxide dismutase (SOD, 52%) and glutathione (GSH, 75%) contents. Correlation analysis identified a significant (p0.95). The MPO (r = 0.664) and LPO (r = 0.841) levels were also correlated with clinical disease state in chagasic subjects (p<0.001). Seronegative/cardiac subjects exhibited up to 77% decline in SOD, 3-5-fold increase in LPO and glutamate pyruvate transaminase (GPT) levels, and statistically insignificant change in MPO, AOPP, MDA, GPX, GSH, and creatine kinase (CK) levels. CONCLUSIONS: The interlinked effects of innate immune responses and antioxidant/oxidant imbalance are major determinants of human Chagas disease. The MPO, LPO and nitrite are excellent biomarkers for diagnosing seropositive/chagasic subjects, and MPO and LPO levels have potential utility in identifying clinical severity of Chagas diseaseFil: Dhiman, Monisha. University Of Texas Medical Branch. Department Of Microbiology & Immunology And Pathology; United State of America;Fil: Coronado, Yun A.. University Of Texas Medical Branch. Department Of Microbiology & Immunology And Pathology; United State of America;Fil: Vallejo, Cecilia K.. University Of Texas Medical Branch. Department Of Microbiology & Immunology And Pathology; United State of America;Fil: Petersen, John R.. University of Texas Medical Branch. Department of Pathology; United States of America;Fil: Ejilemele, Adetoum. University of Texas Medical Branch. Department of Pathology; United States of America;Fil: Nuñez, Sonia. Hospital Público de Gestión Descentralizada San Bernardo (HPGDSA); Argentina;Fil: Zago, María Paola. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - CONICET - Salta. Instituto de Patologia Experimental; Argentina;Fil: Spratt, Heidi. Departments of Biochemistry and Molecular Biology and Preventive Medicine and Community Health. University of Texas Medical Branch; United States of America;Fil: Garg, Nisha Jain. University of Texas Medical Branch. Department of Pathology; United States of America
Disentangling Cooper-pair formation above Tc from the pseudogap state in the cuprates
The discovery of the pseudogap in the cuprates created significant excitement
amongst physicists as it was believed to be a signature of pairing, in some
cases well above the room temperature. In this "pre-formed pairs" scenario, the
formation of pairs without quantum phase rigidity occurs below T*. These pairs
condense and develop phase coherence only below Tc. In contrast, several recent
experiments reported that the pseudogap and superconducting states are
characterized by two different energy scales, pointing to a scenario, where the
two compete. However a number of transport, magnetic, thermodynamic and
tunneling spectroscopy experiments consistently detect a signature of
phase-fluctuating superconductivity above leaving open the question of whether
the pseudogap is caused by pair formation or not. Here we report the discovery
of a spectroscopic signature of pair formation and demonstrate that in a region
of the phase diagram commonly referred to as the "pseudogap", two distinct
states coexist: one that persists to an intermediate temperature Tpair and a
second that extends up to T*. The first state is characterized by a doping
independent scaling behavior and is due to pairing above Tc, but significantly
below T*. The second state is the "proper" pseudogap - characterized by a
"checker board" pattern in STM images, the absence of pair formation, and is
likely linked to Mott physics of pristine CuO2 planes. Tpair has a universal
value around 130-150K even for materials with very different Tc, likely setting
limit on highest, attainable Tc in cuprates. The observed universal scaling
behavior with respect to Tpair indicates a breakdown of the classical picture
of phase fluctuations in the cuprates.Comment: 9 pages, 4 figure
Molecular Cloning of a New Immunomodulatory Protein from Anoectochilus formosanus which Induces B Cell IgM Secretion through a T-Independent Mechanism
An immunomodulatory protein (IPAF) was purified and cloned from Anoectochilus formosanus, an Orchidaceae herbal plant in Asia. The major targeting immune cells of IPAF and its modulating effects toward B lymphocytes were investigated. Rapid amplification of cDNA ends (RACE) was conducted to clone the IPAF gene, and the obtained sequence was BLAST compared on the NCBI database. MACS-purified mouse T and B lymphocytes were stimulated with IPAF and the cell proliferation, activation, and Igs production were examined. IPAF comprised a 25 amino acids signal peptide and a 138 amino acids protein which was homologous to the lectins from Orchidaceae plant. IPAF selectively induced the cell proliferation in mouse splenic B lymphocytes but not T lymphocytes. The IPAF-induced B cells exhibited increased CD69 and MHC class II expression, and a dose- and time-dependent enhancement in IgM production. These results suggested potential benefits of IPAF to strengthen the humoral immunity
Temporal and Spatial Dynamics of Carbon Fixation by Moso Bamboo (Phyllostachys pubescens) in Subtropical China
To study the temporal and spatial dynamics of carbon fixation by Moso bamboo (Phyllostachys pubescens) in subtropical China, carbon fixation of leaves within the canopy of P. pubescens was measured with a LI-6400 portable photosynthesis system. The results showed that the capability of carbon fixation of P. pubescens leaves had obvious temporal and spatial dynamic variations. It was revealed that there were two peak periods and two low periods in the season variation of carbon fixation capability. Data also revealed that the capability of carbon fixation by five-year-old P. pubescens was more than that of one-year-old and three-year-old. Daily and seasonal carbon fixation showed a negative correlation with the CO2 concentration. The temporal and spatial dynamics of carbon fixation by P. pubescens described above provided a scientific basis for development of technologies in bamboo timber production
Quasi-particle interference and superconducting gap in a high-temperature superconductor Ca2-xNaxCuO2Cl2
High-transition-temperature (high-Tc) superconductivity is ubiquitous in the
cuprates containing CuO2 planes but each cuprate has its own character. The
study of the material dependence of the d-wave superconducting gap (SG) should
provide important insights into the mechanism of high-Tc. However, because of
the 'pseudogap' phenomenon, it is often unclear whether the energy gaps
observed by spectroscopic techniques really represent the SG. Here, we report
spectroscopic imaging scanning tunneling microscopy (SI-STM) studies of
nearly-optimally-doped Ca2-xNaxCuO2Cl2 (Na-CCOC) with Tc = 25 ~ 28 K. They
enable us to observe the quasi-particle interference (QPI) effect in this
material, through which unambiguous new information on the SG is obtained. The
analysis of QPI in Na-CCOC reveals that the SG dispersion near the gap node is
almost identical to that of Bi2Sr2CaCu2Oy (Bi2212) at the same doping level,
while Tc of Bi2212 is 3 times higher than that of Na-CCOC. We also find that SG
in Na-CCOC is confined in narrower energy and momentum ranges than Bi2212. This
explains at least in part the remarkable material dependence of TcComment: 13pages, 4fig
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