bluuebunny/crossref_metadata_2025 huggingface dataset:
One Percent Tenofovir Applied Topically to Humanized BLT Mice and Used According to the CAPRISA 004 Experimental Design Demonstrates Partial Protection from Vaginal HIV Infection, Validating the BLT Model for Evaluation of New Microbicide Candidates
Authors: Denton Paul W. , Othieno Florence , Martinez-Torres Francisco , Zou Wei , Krisko John F. , Fleming Elisa , Zein Sima , Powell Daniel A. , Wahl Angela , Kwak Youn Tae , Welch Brett D. , Kay Michael S. , Payne Deborah A. , Gallay Philippe , Appella Ettore , Estes Jacob D. , Lu Min , Garcia J. Victor
Published: May 2011

Recent iPrEx clinical trial results provided evidence that systemic preexposure prophylaxis (PrEP) with emtricitabine (FTC) and tenofovir disoproxil fumarate (TDF) can partially prevent rectal HIV transmission in humans. Similarly, we have previously demonstrated that systemic administration of the same FTC-TDF combination efficiently prevented rectal transmission in humanized bone marrow/liver/thymus (BLT) mice. The CAPRISA 004 trial recently demonstrated that topical application of the tenofovir could partially prevent vaginal HIV-1 transmission in humans. To further validate the usefulness of the BLT mouse model for testing HIV prevention strategies, we evaluated the topical administration of tenofovir as used in CAPRISA 004 to prevent vaginal HIV transmission in BLT mice. Our results demonstrate that vaginally administered 1% tenofovir significantly reduced HIV transmission in BLT mice (P= 0.002). Together with the results obtained after systemic antiretroviral PrEP, these topical inhibitor data serve to validate the use of humanized BLT mice to evaluate both systemic and topical inhibitors of HIV transmission. Based on these observations, we tested six additional microbicide candidates for their ability to prevent vaginal HIV transmission: a C-peptide fusion inhibitor (C52L), a membrane-disrupting amphipathic peptide inhibitor (C5A), a trimericd-peptide fusion inhibitor (PIE12-Trimer), a combination of reverse transcriptase inhibitors (FTC-TDF), a thioester zinc finger inhibitor (TC247), and a small-molecule Rac inhibitor (NSC23766). No protection was seen with the Rac inhibitor NSC23766. The thioester compound TC247 offered partial protection. Significant protection was afforded by FTC-TDF, and complete protection was offered by three different peptide inhibitors tested. Our results demonstrate that these effective topical inhibitors have excellent potential to prevent vaginal HIV transmission in humans.
Reduction of CD4+T CellsIn VivoDoes Not Affect Virus Load in Macaque Elite Controllers
Authors: Mudd Philip A. , Ericsen Adam J. , Price Andrew A. , Wilson Nancy A. , Reimann Keith A. , Watkins David I.
Published: May 2011

A small percentage of human immunodeficiency virus (HIV)- and simian immunodeficiency virus (SIV)-infected individuals spontaneously control virus replication. The majority of these elite controllers mount high-frequency virus-specific CD4+T cell responses. To evaluate the role these responses might play in viral control, we depleted two elite controller macaques of CD4+cells. SIV-specific CD4+T cell responses did not return to baseline levels until 8 weeks postdepletion. Viral loads remained stable throughout the experiment, suggesting that SIV-specific CD4+T cell responses may not play a direct role in controlling chronic viral replication in these elite controllers.
Kaposi's Sarcoma-Associated Herpesvirus vFLIP and Human T Cell Lymphotropic Virus Type 1 Tax Oncogenic Proteins Activate IκB Kinase Subunit γ by Different Mechanisms Independent of the Physiological Cytokine-Induced Pathways
Authors: Shimizu Akira , Baratchian Mehdi , Takeuchi Yasu , Escors David , Macdonald Douglas , Barrett Tracey , Bagneris Claire , Collins Mary , Noursadeghi Mahdad
Published: May 2011

Activation of IκB kinase subunit γ (IKKγ), a key regulator of the classical NF-κB pathway, by the vFLIP protein of Kaposi's sarcoma-associated herpesvirus (KSHV) and the Tax protein of human T cell lymphotropic virus type 1 (HTLV1) is essential for virus-associated cancer. We show that vFLIP and Tax activate this pathway by different interactions with IKKγ and independently of the ubiquitin-mediated signaling pathways induced by cytokines. Our data provide new insights into the mechanisms by which IKKγ can be activated and show that NF-κB activation by oncogenic viruses can be targeted without affecting physiologically important pathways.
Contribution of Topology Determinants of a Viral Movement Protein to Its Membrane Association, Intracellular Traffic, and Viral Cell-to-Cell Movement
Authors: Genovés A. , Pallás V. , Navarro J. A.
Published: May 2011

The p7B movement protein (MP) of
Melon necrotic spot virus
(MNSV) is a single-pass membrane protein associated with the endoplasmic reticulum (ER), the Golgi apparatus (GA), and plasmodesmata (Pd). Experimental data presented here revealed that the p7B transmembrane domain (TMD) was sufficient to target the green fluorescent protein (GFP) to ER membranes. In addition, the short extramembrane regions of p7B were essential for subsequent ER export and transport to the GA and Pd. Microsomal partitioning and bimolecular fluorescence assays supported a type II topology of p7B
in planta
. Mutations affecting conventional determinants of p7B membrane topology, such as the TMD secondary structure, the overall hydrophobicity profile, the so-called “aromatic belt,” and the net charge distribution on either side of the TMD, were engineered into infectious RNAs to investigate the relationship between the MP structure and MNSV cell-to-cell movement. The results revealed that (i) the overall hydrophobic profile and the α-helix integrity of the TMD were relevant for virus movement, (ii) modification of the net charge balance of the regions flanking both TMD sides drastically reduced cell-to-cell movement, (iii) localization of p7B to the GA was necessary but not sufficient for virus movement, and (iv) membrane insertion was essential for p7B function in virus movement. Our results therefore indicate that MNSV cell-to-cell movement requires sequential transport of p7B from the ER via the GA to Pd, which is modulated by a combination of several signals with different strengths in the extramembrane regions and TMD of the MP.
Cytomegalovirus pUL96 Is Critical for the Stability of pp150-Associated Nucleocapsids
Authors: Tandon Ritesh , Mocarski Edward S.
Published: May 2011

Maturation of human cytomegalovirus (HCMV) initiates with nucleocapsids that egress from the nucleus and associate with a juxtanuclear cytoplasmic assembly compartment, where virion envelopment and release are orchestrated. Betaherpesvirus conserved proteins pp150 (encoded by UL32) and pUL96 are critical for HCMV growth in cell culture. pp150 is a capsid-proximal tegument protein that preserves the integrity of nucleocapsids during maturation. pUL96, although expressed as an early protein, acts late during virus maturation, similar to pp150, based on the comparable antigen distribution in UL96, UL32, or UL96/UL32 dual mutant virus-infected cells. pp150 associates with nuclear capsids prior to DNA encapsidation, whereas both pp150 and pUL96 associate with extracellular virus, suggesting that pUL96 is added after pp150. In the absence of pUL96, capsid egress from the nucleus continues; however, unlike wild-type virus infection, pp150 accumulates in the nuclear, as well as in the cytoplasmic, compartment. Ultrastructural evaluation of a UL96 conditional mutant revealed intact nuclear stages but aberrant nucleocapsids accumulating in the cytoplasm comparable to the known phenotype of UL32 mutant virus. In summary, pUL96 preserves the integrity of pp150-associated nucleocapsids during translocation from the nucleus to the cytoplasm.
Role of Interleukin-1 and MyD88-Dependent Signaling in Rhinovirus Infection
Authors: Stokes Clare A. , Ismail Saila , Dick Emily P. , Bennett Julie A. , Johnston Sebastian L. , Edwards Michael R. , Sabroe Ian , Parker Lisa C.
Published: May 2011

Rhinoviral infection is an important trigger of acute inflammatory exacerbations in patients with underlying airway disease. We have previously established that interleukin-1β (IL-1β) is central in the communication between epithelial cells and monocytes during the initiation of inflammation. In this study we explored the roles of IL-1β and its signaling pathways in the responses of airway cells to rhinovirus-1B (RV-1B) and further determined how responses to RV-1B were modified in a model of bacterial coinfection. Our results revealed that IL-1β dramatically potentiated RV-1B-induced proinflammatory responses, and while monocytes did not directly amplify responses to RV-1B alone, they played an important role in the responses observed with our coinfection model. MyD88 is the essential signaling adapter for IL-1β and most Toll-like receptors. To examine the role of MyD88 in more detail, we created stable MyD88 knockdown epithelial cells using short hairpin RNA (shRNA) targeted to MyD88. We determined that IL-1β/MyD88 plays a role in regulating RV-1B replication and the inflammatory response to viral infection of airway cells. These results identify central roles for IL-1β and its signaling pathways in the production of CXCL8, a potent neutrophil chemoattractant, in viral infection. Thus, IL-1β is a viable target for controlling the neutrophilia that is often found in inflammatory airway disease and is exacerbated by viral infection of the airways.
Demographic Processes Affect HIV-1 Evolution in Primary Infection before the Onset of Selective Processes
Authors: Herbeck Joshua T. , Rolland Morgane , Liu Yi , McLaughlin Sherry , McNevin John , Zhao Hong , Wong Kim , Stoddard Julia N. , Raugi Dana , Sorensen Stephanie , Genowati Indira , Birditt Brian , McKay Angela , Diem Kurt , Maust Brandon S. , Deng Wenjie , Collier Ann C. , Stekler Joanne D. , McElrath M. Juliana , Mullins James I.
Published: May 2011

HIV-1 transmission and viral evolution in the first year of infection were studied in 11 individuals representing four transmitter-recipient pairs and three independent seroconverters. Nine of these individuals were enrolled during acute infection; all were men who have sex with men (MSM) infected with HIV-1 subtype B. A total of 475 nearly full-length HIV-1 genome sequences were generated, representing on average 10 genomes per specimen at 2 to 12 visits over the first year of infection. Single founding variants with nearly homogeneous viral populations were detected in eight of the nine individuals who were enrolled during acute HIV-1 infection. Restriction to a single founder variant was not due to a lack of diversity in the transmitter as homogeneous populations were found in recipients from transmitters with chronic infection. Mutational patterns indicative of rapid viral population growth dominated during the first 5 weeks of infection and included a slight contraction of viral genetic diversity over the first 20 to 40 days. Subsequently, selection dominated, most markedly in
env
and
nef
. Mutants were detected in the first week and became consensus as early as day 21 after the onset of symptoms of primary HIV infection. We found multiple indications of cytotoxic T lymphocyte (CTL) escape mutations while reversions appeared limited. Putative escape mutations were often rapidly replaced with mutually exclusive mutations nearby, indicating the existence of a maturational escape process, possibly in adaptation to viral fitness constraints or to immune responses against new variants. We showed that establishment of HIV-1 infection is likely due to a biological mechanism that restricts transmission rather than to early adaptive evolution during acute infection. Furthermore, the diversity of HIV strains coupled with complex and individual-specific patterns of CTL escape did not reveal shared sequence characteristics of acute infection that could be harnessed for vaccine design.
Hereditary thrombophilia in an unselected cohort of venous thrombosis patients in Singapore
Authors: Lee Lai Heng , Liu Te Chih , Kuperan Ponnudurai , Tan Lip Kun , Tan Daryl , Poon Michelle L , Ong Kiat Hoe , Fong Sing Zern , Tan Melissa Y , Ng Heng Joo
Published: May 2011

Aim

Hereditary thrombophilic markers are commonly screened among patients diagnosed as having venous thromboembolism, but optimal patient selection and the goals of screening may differ between populations. Determining the patterns of hereditary thrombophilia may improve screening strategies.

Method

An unselected cohort of venous thromboembolism patients in three tertiary institutions in Singapore was prospectively tested for the prevalence of deficiencies of protein C, protein S, antithrombin III, factor V Leiden and prothrombin 20210 gene mutations.

Results

Among 384 patients screened, the prevalences of protein S, protein C and antithrombin III were 9.20%, 1.18% and 4.19% respectively. Only one patient was positive for the factor V Leiden mutation and none tested positive for the prothrombin 20210 gene mutation. At least 1 in 9 patients (11.52%, 95% CI 8.20 to 15.93) will test positive for one of the above markers in an unselected group of 269 patients who completed all tests. The exclusion of patients with clinical risk factors did not improve the detection rates, in comparison with those with obvious provoking clinical risk factors (11.72%, 95% CI 7.36 to 18.06 vs 11.29%, 95% CI 6.73 to 18.18). When upper age limits were set for thrombophilia screening by decades, a statistical difference in the likelihood of a positive thrombophilia screen between younger and older patient was seen for patients below 40 (p<0.001).

Conclusion

In Singapore and countries with similar demographics, hereditary thrombophilia screening should be confined to testing for protein C, protein S and antithrombin III.
Follicular patterned lesions of the thyroid gland: a practical algorithmic approach
Authors: Chetty Runjan
Published: May 2011

Follicular patterned lesions of the thyroid are problematic and interpretation is often subjective. While thyroid experts are comfortable with their own criteria and thresholds, those encountering these lesions sporadically have a degree of uncertainty with a proportion of cases. The purpose of this review is to highlight the importance of proper diligent sampling of an encapsulated thyroid lesion (in totality in many cases), examination for capsular and vascular invasion, and finally the assessment of nuclear changes that are pathognomonic of papillary thyroid carcinoma (PTC). Based on these established criteria, an algorithmic approach is suggested using known, accepted terminology. The importance of unequivocal, clear-cut nuclear features of PTC as opposed to inconclusive features is stressed. If the nuclear features in an encapsulated, non-invasive follicular patterned lesion fall short of those encountered in classical PTC, but nonetheless are still worrying or concerning, the term ‘uncertain malignant potential or behaviour, most likely benign’ is suggested. Indubitable, classical PTC nuclei (whether diffuse or restricted to a single high-power field) are diagnostic of a PTC be it classical, non-invasive or invasive follicular variant PTC. Capsular and vascular invasion remain the only reliable predictors of outcome, as non-invasive, encapsulated follicular variant PTC, even with diffuse PTC nuclear change, behaves in an indolent fashion.
Acupuncture in Obstetrics and Gynecology: An Overview of Systematic Reviews
Authors: Ernst Edzard , Lee Myeong Soo , Choi Tae-Young
Published: May 2011

Acupuncture is often recommended for obstetrical and gynecological conditions but the evidence is confusing. We aim to summarize all recent systematic reviews in this area. Western and Asian electronic databases were searched for systematic reviews of any type of acupuncture for any type of gynecological conditions. Our own files were hand-searched. Systematic reviews of any type of acupuncture for any type of gynecological conditions were included. Non-systematic reviews and systematic reviews published before 2004 were excluded. No language restrictions were applied. Data were extracted according to predefined criteria and analysed narratively. Twenty-four systematic reviews were included. They relate to a wide range of gynecological conditions: hot flashes, conception, dysmenorrhea, premenstrual syndrome, nausea/vomiting, breech presentation, back pain during pregnancy, and procedural pain. Nine systematic reviews arrived with clearly positive conclusions; however, there were many contradictions and caveats. The evidence for acupuncture as a treatment of obstetrical and gynecological conditions remains limited.
Effects ofPanax ginsengSupplementation on Muscle Damage and Inflammation after Uphill Treadmill Running in Humans
Authors: Jung Hyun Lyung , Kwak Hye Eun , Kim Sung Soo , Kim Young Chan , Lee Chong Do , Byurn Heidi K. , Kang Ho Youl
Published: May 2011

The purpose of this investigation was to determine whether Panax ginseng extract intake would influence exercise-induced muscle damage and inflammation responses. Eighteen male college students were randomly assigned to either an RG intake group (RG, n = 9) or a placebo group (P, n = 9). All subjects performed a high-intensity uphill treadmill running task (two rounds of 45 min at 10 km/h speed with a 15 degree uphill slope separated by 5 min of rest). The RG group ingested 20 g/day of Korean red ginseng extract (mixed with 200 ml of water) three times/day for seven days prior to performing the uphill treadmill exercise test and for four days after the treadmill test, while the P group ingested 200 ml of water containing Agastachis Herba on the same schedule. Plasma creatine kinase activity (CK) and interlukin-6 (IL-6) levels were measured at pre-exercise and 24, 48, 72, and 96 h post-exercise; the IL-6 level was also measured at 1 and 2 h post-exercise. To evaluate insulin sensitivity, the oral glucose tolerance test (OGTT) was performed 24 h post-exercise. Plasma CK level in RG was significantly lower than that in P 72 h post-exercise (p < 0.05), and IL-6 level was significantly decreased in RG during the 2 h and 3 h recovery period compared to that of P (p < 0.05). Plasma glucose and insulin responses in RG were significantly reduced compared to those of P (p < 0.05). The results of this study suggest that RG supplementation could reduce exercise-induced muscle damage and inflammatory responses, resulting in improvements in insulin sensitivity.
Efficacy and Safety of Orally Administered Lentinula edodes Mycelia Extract for Patients Undergoing Cancer Chemotherapy: A Pilot Study
Authors: Yamaguchi Yoshiyuki , Miyahara Eiji , Hihara Jun
Published: May 2011

Lentinula edodes mycelia extract (L.E.M.) is extensively utilized as an herbal medicine. However, its safety and effectiveness have not yet been scientifically verified. In this study, we investigated its safety and its influence on quality of life (QOL) and the immune response in patients undergoing cancer chemotherapy. Seven patients were studied in total. The patients were undergoing postoperative adjuvant chemotherapy for breast cancer (n = 3) or gastrointestinal cancer (n = 2), or were receiving chemotherapy to prevent recurrence of gastrointestinal cancer (n = 2). The first course of treatment was chemotherapy alone and the second was chemotherapy plus concomitant administration of L.E.M. Adverse events and changes in the QOL score, lymphocyte subpopulations, lymphocyte activity and serum immune indices were evaluated during the study period. No adverse events attributable to L.E.M. were observed. Compared to the pre-chemotherapy state, no changes in QOL or immune parameters were noted after the first chemotherapy course. In contrast, following the second course of combined therapy, improvements were noted in QOL (p < 0.05), NK cell activity (p < 0.05) and immunosuppressive acidic protein (IAP) (p < 0.01) levels. Although a future large-scale investigation is necessary to confirm these results, these data suggest that the concomitant of L.E.M. with chemotherapy is safe and improves the QOL and immune function of patients undergoing chemotherapy.
Proteomic Analysis of Effects on Natural Herb Additive Containing Immunoglobulin Yolksac (IgY) in Pigs
Authors: Park Hyeon-Soo , Park Kwang-Il , Nagappan Arulkumar , Lee Do-Hoon , Kang Sang-Rim , Kim Jin-A , Kim Eun Hee , Han Dae-Yong , Kim Gon-Sup
Published: May 2011

Thirty male pigs were infected orally with E. coli and Salmonella typhimurium, and divided into a control group and two additive groups to determine the effect of an additive mixture on the changes in protein expression. The pigs were given a food supplemented with a natural herbal additive containing immunoglobulin yolksac (IgY) at concentrations of 0.5% or 1%. On the 1st day and after eight weeks of feeding, the body weight gain, food intake and serum GOT/GPT levels were examined. The GOT/GPT levels on the 1st day were similar in the three groups. However, after eight weeks of feeding, the GOT level was significantly lower in the additive treatment groups (0.5% and 1.0%). In addition, the changes in the spleen proteome as a response to the herbal additive were examined using two-dimensional polyacrylamide gel electrophoresis. A total of 31 differentially expressed protein spots were identified by comparing the protein profiles of the control and additive treated porcine spleens. Finally, 19 proteins were detected by MALDI-TOF/MS. Overall, the proteins detected are involved in a range of biological process, such as metabolic processes, biological processes, transport, carbohydrate metabolic processes, generation of precursors and energy. In conclusion, these results support of the hypothesis that a natural herbal additive containing IgY can affect the immune regulation system and reduce the stress of microbial infections.
Protective Effects of Atractylodes macrocephala Polysaccharide on Liver Ischemia–Reperfusion Injury and Its Possible Mechanism in Rats
Authors: Jin Cheng , Zhang Pei-Jian , Bao Chuan-Qing , Gu Yuan-Long , Xu Bing-Hua , Li Cheng-Wan , Li Jian-Ping , Bo Ping , Liu Xin-Nong
Published: May 2011

Atractylodes macrocephala polysaccharide (AMP), a traditional Chinese medicine, is thought to have protective effects against liver injury. Therefore, this study was designed to explore the effects of AMP on hepatic ischemia–reperfusion injury (IRI) and elucidate the possible mechanisms. Ninety-six Sprague-Dawley rats were randomly divided into four groups with 24 rats per group: a normal control group, an IRI group, an AMP-treated group (0.4 g/kg/d) and a bifendate-treated group (100 mg/kg). Rats were treated with AMP or bifendate once daily for seven days by gastric gavage. The normal control group and the IRI model group received an equivalent volume of physiological saline. At 1, 6 and 24 h after surgery, the rats were killed and liver tissue samples were obtained to determine interleukin-1 (IL-1) expression by Western blotting and nuclear factor-κB (NF-κB) expression by immunohistochemistry. Liver morphology was assessed by microscopy and transmission electron microscopy. Blood samples were obtained to measure liver function (alanine aminotransferase, aspartate aminotransferase, total bilirubin and direct bilirubin). AMP significantly reduced the elevated expression of markers of liver dysfunction and the hepatic morphologic changes induced by hepatic IRI in rats. AMP also markedly inhibited IRI-induced lipid peroxidation and altered the activities of the antioxidant enzyme superoxide dismutase and malondialdehyde levels. Moreover, pretreatment with AMP suppressed the expression of interleukin-1β and NF-kB in IRI-treated rats. These results suggest that AMP exerts protective and therapeutic effects against hepatic IRI in rats, which might be associated with its antioxidant properties and inhibition of NF-κB activation. More studies are needed to better understand the mechanisms underlying the protective effects of AMP on hepatic IRI.
Hepatoprotective Effect of Crossostephium chinensis (L.) Makino in Rats
Authors: Chang Tien-Ning , Ho Yu-Ling , Huang Guan-Jhong , Huang Shyh-Shyun , Chen Chao-Jung , Hsieh Po-Chow , Chiang Ying-Chen , Chang Yuan-Shiun
Published: May 2011

The hepatoprotective potential of Crossostephium chinensis (L.) Makino water extract (CCW) on carbon tetrachloride ( CCl 4) induced liver damage was evaluated in preventive and curative rat models. Not only were indicators of hepatic damage including GPT, GOT, lipid peroxides and TBARS were examined, the activities of antioxidant enzymes (SOD, CAT, GPx) and GSH were examined as well. The results showed that CCW (0.1, 0.5 and 1.0 g/kg) significantly reduced the elevated levels of GPT and GOT by CCl 4 administration (p < 0.05). TBARS level was dramatically reduced, and SOD, CAT, GPx and GSH activities were significantly increased. In addition, CCW decreased NO production and TNF-α activation in CCl 4-treated rats. Therefore, we speculate that CCW protects against acute liver damage through its radical scavenging ability. CCW inhibited the expression of MMP-9 protein, indicating that MMP-9 played an important role in the development of CCl 4-induced chronic liver damage in rats. In LC-MS-MS analysis, the chromatograms of CCW with good hepatoprotective activities were established. Scopoletin may be an important bioactive compound in CCW.
Effects and Mechanisms ofAcremoniumterricola milleretal myceliumon Liver Fibrosis Induced by Carbon Tetrachloride in Rats
Authors: Tian Xiao-Peng , Yin Yan-Yan , Li Xia
Published: May 2011

Acremoniumterricola milleretal mycelium (AMM) is one of the most precious traditional Chinese medicines. It has numerous protective effects on organs, and has been used in Chinese herb prescription to treat refractory diseases. Our preliminary studies demonstrated that AMM had hepatoprotective activity in acute liver injury. We further investigated the effects of AMM on liver fibrosis in rats induced by carbon tetrachloride ( CCl4) and explore its possible mechanisms. The animal model was established by injection with 50% CCl4subcutaneously in male Sprague-Dawley rats twice a week for eight weeks. Meanwhile, AMM (175, 350 and 700 mg/kg) was administered intragastrically per day until sacrifice. We found that treatment with AMM (175, 350 and 700 mg/kg) decreased CCl4-induced elevation of serum transaminase activities, hyaluronic acid, laminin and procollagen type III levels, and contents of hydroxyproline in liver tissues. It also restored the decreased SOD and GSH-Px activities and inhibited the formation of lipid peroxidative products during CCl4treatment. Moreover, AMM (350 and 700 mg/kg) decreased the elevation of TGF-β1 by 19.6% and 34.3%, respectively. In the pathological study, liver injury and the formation of liver fibrosis in rates treated by AMM were improved significantly. Immunoblot analysis showed that AMM (175, 350 and 700 mg/kg) inhibited Smad 2/3 phosphorylation, and elevated inhibitor Smad 7 expression. These results suggested that AMM could protect liver damage and inhibit the progression of hepatic fibrosis induced by CCl4, and its mechanisms might be associated with its ability to scavenge free radicals, decrease the level of TGF-β1 and block TGF-β/Smad signaling pathway.
Effect ofOrostachys japonicuson Cell Growth and Apoptosis in Human Hepatic Stellate Cell Line LX2
Authors: Kim Young Il , Park Seung-Won , Choi In-Hwa , Lee Jang-Hoon , Woo Hong-Jung , Kim Youngchul
Published: May 2011

Orostachys japonicus (O. japonicus), used to treat diseases such as various cancers, gastric ulcers, fever, hepatitis, arthritis, eczema, for hemostasis, and intoxication in folk medicine, has been an important constituent in many herbal formulae. We demonstrated that the water extract of O. japonicus led to growth inhibition of LX2 cells by inducing apoptosis through the caspase activation, related to the MAPK pathway. O. japonicus inhibited proliferation of LX2 cells in a dose- and time-dependent manner, increased the apoptosis fraction at cell cycle progression with an accompanying DNA fragmentation, and resulted in a significant decrease in Bcl-2 and an increase in Bax mRNA levels. Exposure of LX2 cells to O. japonicus induced caspase-3 activation, however when the LX2 cells were also treated with the pan-caspase inhibitor Z-VAD-FMK and the caspase-3 inhibitor Z-DEVE-FMK, apoptosis was blocked. O. japonicus inhibited anti-apoptotic Mcl-1 protein and MEK/ERK phosphorylation in LX2 cells. The results indicate that O. japonicus inhibits the cell growth of LX2 cells by inducing apoptosis through caspase activity. O. japonicus down-regulated Mcl-1 protein levels and inhibited the phosphorylation of MEK/ERK, suggesting that it mediates cell death in LX2 cells through the down-regulation of Mcl-1 protein via a MEK/ERK-independent pathway.
Chemical Composition Analysis, Antioxidant, Antiglycating Activities and Neuroprotective Effects ofS. choloroleuca, S. mirzayanii and S. santolinifoliafrom Iran
Authors: Asadi Sareh , Khodagholi Fariba , Esmaeili Mohammad Ali , Tusi Solaleh Khoramian , Ansari Niloufar , Shaerzadeh Fatemeh , Sonboli Ali , Ghahremanzamaneh Mina
Published: May 2011

This study was designed to examine antioxidant activities, antiglycating abilities and neuroprotective effects of methanolic extracts of Salvia choloroleuca, Salvia santolinifolia and Salvia mirzayanii from Iran. The extracts were screened for their possible antioxidant activities by several biochemical assays such as DPPH, FRAP, β-carotene bleaching and TEAC assays. HPLC analysis of these extracts led to the separation of a number of components such as catechine and rosmarinic acid. Based on our results, all these plants had antioxidant and antiglycating activities, among them S. choloroleuca seems to be the most effective one. Furthermore, these species not only showed no cytotoxic effects in neuron-like PC12 cells, but also protected them against oxidative stress-induced cell death, exerted by H2O2. We further showed that these plants increase superoxide dismutase and catalase levels, reduce lipid peroxidation and up regulate hemeoxygenase-1 and glutamylcysteine synthetase proteins. This study raised the possibility of developing these plants as potential neuroprotective agents.
FROM METHODS OF THE MATHEMATICAL KINETIC THEORY FOR ACTIVE PARTICLES TO MODELING VIRUS MUTATIONS
Authors: DELITALA M. , PUCCI P. , SALVATORI M. C.
Published: May 2011

The paper presents a model of virus mutations and evolution of epidemics in a system of interacting individuals, where the intensity of the pathology, described by a real discrete positive variable, is heterogeneously distributed, and the virus is in competition with the immune system or therapeutical actions. The model is developed within the framework of the Kinetic Theory of Active Particles. The paper also presents a qualitative analysis developed to study the well-posedness of the mathematical problem associated to the general framework. Finally, simulations show the ability of the model to predict some interesting emerging phenomena, such as the mutation to a subsequent virus stage, the heterogeneous evolution of the pathology with the co-presence of individual carriers of the virus at different levels of progression, and the presence of oscillating time phases with either virus prevalence or immune system control.
PARTICLE DYNAMICS IN WEAKLY CHARGED EXTREME KERR THROAT
Authors: AL ZAHRANI A. M. , FROLOV VALERI P. , SHOOM ANDREY A.
Published: May 2011

We study dynamics of a test charged particle moving in a weakly charged extreme Kerr throat. Dynamical equations of the particle motion are solved in quadratures. We show explicitly that the Killing tensor of the Kerr spacetime becomes reducible in the extreme Kerr throat geometry. Special types of motion of particles and light are discussed.
ON THE DYNAMICS OF A CLASS OF EINSTEIN–VLASOV SHELLS
Authors: GLEISER REINALDO J. , RAMIREZ MARCOS A.
Published: May 2011

The Einstein–Vlasov equations govern the dynamics of systems of self-gravitating collisionless particles in the framework of general relativity. Here we review some recent results obtained by restricting to spherically symmetric systems and imposing the simplifying restrictions that the conserved angular momentum of the particles can take values only on a discrete, finite set. The first set of results is restricted to the existence of thin shells, their dynamics and stability. A second set is concerned with the existence of thick shells satisfying the same restrictions and the conditions under which they admit, in general, a thin shell limit. In a related result it is shown that the so called Einstein shells have a unique thin shell limit where the particle's angular momentum has a continuous distribution.
MEASUREMENTS OF COSMIC RAYS AT THE HIGHEST ENERGIES WITH THE PIERRE AUGER OBSERVATORY
Authors:   for the Pierre Auger Collaboration, HARARI DIEGO
Published: May 2011

Measurements with the Pierre Auger Observatory indicate with unprecedented statistics that the flux of cosmic rays is strongly suppressed above 4 × 1019 eV. The suppression is consistent with the prediction that cosmic rays with larger energies can only arrive from nearby sources due to their interaction with the cosmic microwave background, but could also be related to the efficiency of the acceleration processes at the sources. The Observatory has found independent evidence of the nearby extragalactic origin of cosmic rays with energy above ~6×1019 eV with a measurement of the fraction of arrival directions that correlate with the positions of active galactic nuclei within ~100 Mpc. This correlation does not identify active galaxies as the sites of origin, since their distribution traces the overall local matter distribution. We review recent measurements made with the Pierre Auger Observatory of the flux, anisotropy and composition of CRs.
QUANTUM SINGULARITIES IN STATIC SPACETIMES
Authors: PITELLI JOÃO PAULO M. , LETELIER PATRICIO S.
Published: May 2011

We review the mathematical framework necessary to understand the physical content of quantum singularities in static spacetimes. We present many examples of classical singular spacetimes and study their singularities by using wave packets satisfying Klein–Gordon and Dirac equations. We show that in many cases the classical singularities are excluded when tested by quantum particles but unfortunately there are other cases where the singularities remain from the quantum mechanical point of view. When it is possible we also find, for spacetimes where quantum mechanics does not exclude the singularities, the boundary conditions necessary to turn the spatial portion of the wave operator to be self-adjoint and emphasize their importance to the interpretation of quantum singularities.
FOUNDATIONS OF QUANTUM MECHANICS: DECOHERENCE AND INTERPRETATION
Authors: LOMBARDI OLIMPIA , ARDENGHI JUAN SEBASTIAN , FORTIN SEBASTIAN , NARVAJA MARTIN
Published: May 2011

In this paper, we review Castagnino's contributions to the foundations of quantum mechanics. First, we recall his work on quantum decoherence in closed systems, and the proposal of a general framework for decoherence from which the phenomenon acquires a conceptually clear meaning. Then, we introduce his contribution to the hard field of the interpretation of quantum mechanics: the modal-Hamiltonian interpretation solves many of the interpretive problems of the theory, and manifests its physical relevance in its application to many traditional models of the practice of physics. In the third part of this work we describe the ontological picture of the quantum world that emerges from the modal-Hamiltonian interpretation, stressing the philosophical step toward a deep understanding of the reference of the theory.
PATH INTEGRALS FOR QUASI-HERMITIAN HAMILTONIANS
Authors: RIVERS R. J.
Published: May 2011

Inner products in quasi-Hermitian quantum theories, and hence probabilities, are defined through a metric that depends on the details of the Hamiltonians themselves. We shall see that the functional integral for quasi-Hermitian theories, and hence Feynman diagrams, for example, can be calculated without needing to evaluate the metric. The reason turns out be that their derivation is based fundamentally on the Heisenberg equations of motion and the canonical equal-time commutation relations, which retain their standard form. As an application, we show how co-ordinate transformations in the path integral can enable us to recover equivalent Hermitian Hamiltonians.
CHARGE CONJUGATION FROM SPACE-TIME INVERSION IN QED: DISCRETE AND CONTINUOUS GROUPS
Authors: PÉREZ B. CARBALLO , SOCOLOVSKY M.
Published: May 2011

We show that the CPT groups of QED emerge naturally from the [Formula: see text] and [Formula: see text] (or [Formula: see text]) subgroups of the Lorentz group. We also find relationships between these discrete groups and continuous groups, like the connected Lorentz and Poincaré groups and their universal coverings.
CAN WE LEARN SOMETHING ABOUT THE QUANTUM/GRAVITY INTERFACE FROM THE PRIMORDIAL FLUCTUATION SPECTRUM?
Authors: SUDARSKY DANIEL
Published: May 2011

The explanation about the origin of cosmic structure, provided by the standard inflationary paradigm, is not fully satisfactory, as has been argued in [A. Perez, H. Sahlmann, and D. Sudarsky, Class. Quant. Grav.23 (2006) 2317]. The central point of that work is that something important is missing in our understanding of the origin of the seeds of cosmic structure, as is evidenced by the fact that, in the standard accounts, the inhomogeneity and anisotropy of our universe seems to emerge from an exactly homogeneous and isotropic initial state through processes that can not break those symmetries. We review here the problem and the proposal to address this shortcoming in terms of dynamical collapse of the original vacuum of the inflaton field, and indicate how it might be connected to other issues facing the study of the quantum/gravity interface.
NAKED SINGULARITIES, TOPOLOGICAL DEFECTS AND BRANE COUPLINGS
Authors: EDELSTEIN JOSÉ D. , GARBARZ ALAN , MIŠKOVIĆ OLIVERA , ZANELLI JORGE
Published: May 2011

A conical defect in 2 + 1 anti-de Sitter space is a BTZ solution with a negative mass parameter. This is a naked singularity, but a rather harmless one: it is a point particle. Naturally, the energy density and the spacetime curvature have a δ-like singularity at the conical defect, but that does not give rise to any unphysical situations. Since the conical solution implies the presence of a source, applying reverse enginnering, one can identify the coupling term that is required in the action to account for that source. In that way, a relation is established between the identification operation that gives rise to the topological defect and the interaction term in the action that produces it. This idea has a natural extension to higher dimensions, where instead of a point particle (zero-brane) one finds membranes of even spatial dimensions (p-branes, with p = 2n). The generalization to other abelian and nonabelian gauge theories — including (super-) gravities — is fairly straightforward: the 2n-brane couples to a (2n + 1) Chern–Simons form. The construction suggests a generic role for Chern–Simons forms as the natural way to couple a gauge connection to a brane and avoids the inconsistency that results from the minimal coupling between a brane and a fundamental p-form field.
METRIC FLUCTUATIONS IN DE SITTER SPACETIME IN STOCHASTIC GRAVITY
Authors: VERDAGUER ENRIC
Published: May 2011

Stochastic gravity extends semiclassical gravity by allowing for a systematic and self-consistent description of the metric fluctuations produced by the quantum fluctuations of the stress tensor. The effect of minimally coupled scalar fields with arbitrary mass in de Sitter spacetime is discussed, assuming that these fields are in the Bunch–Davies de Sitter invariant vacuum. The matter field fluctuations are described by the noise kernel which is obtained from the symmetrized two-point correlation of the stress tensor operator. The noise kernel is computed in terms of de Sitter invariant bi-tensors. It turns out that in a de Sitter background the two-point function of the linearized Einstein tensor, which is gauge invariant, is directly related to the noise kernel.
TOPOLOGICAL EFFECTS IN QUANTUM MECHANICS AND HIGH VELOCITY ESTIMATES
Authors: WEDER RICARDO
Published: May 2011

We consider the problem of obtaining high-velocity estimates for finite energy solutions (wave packets) to Schrödinger equations for N-body systems. We discuss a time-dependent method that allows us to obtain precise estimates with error bounds that decay as a power of the velocity. We apply this method to the electric Aharonov–Bohm effect. We give the first rigorous proof that quantum mechanics predicts the existence of this effect. Our result follows from an estimate in norm, uniform in time, that proves that the Aharonov–Bohm Ansatz is a good approximation to the exact solution to the Schrödinger equation for high velocity.
ENHANCEMENT OF INTEGRATED EARTHQUAKE SIMULATION WITH HIGH-PERFORMANCE COMPUTING
Authors: HORI M. , SOBHANINEJAD G. , ICHIMURA T. , LALITH M.
Published: May 2011

Integrated earthquake simulation (IES) is a system to estimate possible earthquake hazard and disaster which can take place in an urban area by means of seamless numerical computation. High-performance computing (HPC) is enhanced so that IES is able to simulate a larger area in a shorter time, by improving the system architecture and adding new elements which smoothens the system's efficiency. It is shown in numerical experiments (which are carried out for actual urban areas) that the performance of IES enhanced with HPC is satisfactory. A new system is developed to generate a hazard map which depicts earthquake damages in higher spatial resolution by taking advantage of IES enhanced with HPC. It is shown that such maps can be generated for Tokyo metropolis in half a day.
ISOLATED EFFECTION OF THE XIAZHANG CROSS-SEA ISOLATED BRIDGE
Authors: YUAN YONG , ZHU HONG PING
Published: May 2011

In this study, the real-time hybrid loading test system based on the velocity-based loading concept is developed. The test system utilizes the concepts of the real-time hybrid loading test method and the substructure technique to combine the loading process of rubber-bearing specimens and numerical modeling of bridge columns and girders. Newly developed components of the loading test system include: an axial loading device especially devised for the fast loading of rubber bearings, and a real-time test control algorithm using the velocity-based loading concept, implemented to a PC-DSP system framework for the actuator control signal processing. A series of real–time hybrid loading tests on natural rubber (NR), high-damping rubber (HDR), and super-high-damping rubber (HDR-s) bearings are conducted using the test system. The objective of this study is to pursue accurate prediction of the dynamic response and base isolation effects of rubber bearings under realistic earthquake conditions. Specifially, the base isolation effects of HDR-s bearing are discussed. Based on the test results, it is clarified that the HDR-s bearing is more effective than the HDR and NR bearings.
MINOR DAMAGE DETECTION USING CHAOTIC EXCITATION AND RECURRENCE ANALYSIS
Authors: SATO TADANOBU , TANAKA YOUHEI
Published: May 2011

In this paper, we propose a new attractor-based structural damage detection technique using chaotic excitation. Attractor is reconstructed using vibration response data and sensitive to the change of the system dynamics. By comparing the change of attractors from healthy and damaged structures, we detect and localize the damage. We use recurrence analysis to analyze the change of attractor. Numerical example demonstrates the robustness and sensitivity of the proposed method.
LATERAL SPREADING DAMAGE TO SHEET-PILE WALLS AND PILE FOUNDATIONS REPRODUCED BY TSUKUBA LARGE-SCALE SHAKE TABLE
Authors: SATO MASAYOSHI , TABATA KENTARO
Published: May 2011

Shaking table tests of two large-scale models with lateral spreading of liquefiable deposit under earthquake ground motions were performed to reveal the failure mechanism of sheet-pile-type quay walls and pile foundations behind them. These tests simulated the lateral spreading behavior of the deposit with slow rate of ground deformation, which was assumed to occur even after earthquake shaking. The test results also indicated that a deposit's residual deformation induced by the cyclic motions due to an earthquake and a structure's inertial force largely influence the deformations of the quay wall and the pile foundation.
FUNCTIONAL NEAR-INFRARED SPECTROSCOPY–BASED ASSESSMENT OF ATTENTION IMPAIRMENTS AFTER TRAUMATIC BRAIN INJURY
Authors: MERZAGORA ANNA C. , SCHULTHEIS MARIA T. , ONARAL BANU , IZZETOGLU MELTEM
Published: May 2011

A frequent consequence of traumatic brain injury (TBI) is cognitive impairment, which results in significant disruption of an individual's everyday living. To date, most clinical rehabilitation interventions still rely on behavioral observation, with little or no quantitative information about physiological changes produced at the brain level. Functional brain imaging has been extensively used in the study of cognitive impairments following TBI. However, its applications to rehabilitation have been limited. This is due in part to the expensive or invasive nature of these modalities. The objective of this study is to apply functional near-infrared spectroscopy (fNIR) to the assessment of attention impairments following TBI. fNIR provides a localized measure of prefrontal hemodynamic activation, which is susceptible to TBI, and it does so in a noninvasive, affordable and wearable way, thus partially overcoming the limitations of other modalities. Participants included 5 TBI subjects and 11 healthy controls. Brain activation measurements were collected during a target categorization task. Significant differences were found in the hemodynamic response between healthy and TBI subjects. In particular, the elicited responses exhibited reduced amplitude in the TBI group. Overall, the results provide first evidence of the ability of fNIR to reveal differences between TBI and healthy subjects in an attention task. fNIR is therefore a promising neuroimaging technique in the field of neurorehabilitation. The use of fNIR in neurorehabilitation applications would benefit from its noninvasiveness and cost-effectiveness and the neurophysiological information obtained through the evaluation of the hemodynamic activation could provide invaluable information to guide the choice of intervention.
PDGF-dependent regulation of regulator of G protein signaling-5 expression and vascular smooth muscle cell functionality
Authors: Gunaje Jagadambika J. , Bahrami Arya J. , Schwartz Stephen M. , Daum Guenter , Mahoney William M.
Published: May 2011

Regulator of G protein signaling (RGS) proteins, and notably members of the RGS-R4 subfamily, control vasocontractility by accelerating the inactivation of Gα-dependent signaling. RGS5 is the most highly and differently expressed RGS-R4 subfamily member in arterial smooth muscle. Expression of RGS5 first appears in pericytes during development of the afferent vascular tree, suggesting that RGS5 is a good candidate for a regulator of arterial contractility and, perhaps, for determining the mass of the smooth muscle coats required to regulate blood flow in the branches of the arterial tree. Consistent with this hypothesis, using cultured vascular smooth muscle cells (VSMCs), we demonstrate RGS5 overexpression inhibits G protein-coupled receptor (GPCR)-mediated hypertrophic responses. The next objective was to determine which physiological agonists directly control RGS5 expression in VSMCs. GPCR agonists failed to directly regulate RGS5 mRNA expression; however, platelet-derived growth factor (PDGF) acutely represses expression. Downregulation of RGS5 results in the induction of migration and the activation of the GPCR-mediated signaling pathways. This stimulation leads to the activation of mitogen-activated protein kinases directly downstream of receptor stimulation, and ultimately VSMC hypertrophy. These results demonstrate that RGS5 expression is a critical mediator of both VSMC contraction and potentially, arterial remodeling.