Examination of Selected Microparticles from the Sentik Glacier Core, Ladakh, Himalayas

Several characteristics and interpretive comments are reported for microparticles from selected samples in the Sentik Glacier core. Four basic morphologic groups are defined: Platy, angular, biogenic, and anomalous

The National Cancer Institute of Canada Clinical Trials Group MAP.3 Trial: An International Breast Cancer Prevention Trial

Several large phase iii trials have demonstrated that tamoxifen—and more recently, raloxifene—can effectively reduce the incidence of invasive breast cancer by 50%. However, these selective estrogen receptor modulators can also be associated with several rare, but serious, adverse events. Recently, the third-generation aromatase inhibitors (AIS) have demonstrated excellent efficacy in adjuvant breast cancer trials, and they show particular promise in the breast cancer prevention setting. The National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) has developed a randomized phase iii study to determine the efficacy of an ai (exemestane) to reduce the incidence of invasive breast cancer in postmenopausal women at an increased risk for developing breast cancer. The ncic ctg map.3 (ExCel) trial is a double-blind placebo-controlled multicentre, multinational trial. Based on the known preclinical and clinical profile of the ais, a greater reduction in breast cancer incidence with fewer side effects is hypothesized with this class of agents than with tamoxifen or raloxifene

Effects of Liarozole Fumarate (R85246) in Combination with Tamoxifen on N-methyl-N-nitrosourea (MNU)-induced Mammary Carcinoma and Uterus in the Rat Model

Background: Liarozole fumarate (liarozole – R85246) is a novel compound with characteristics of both aromatase inhibitor (AI) and a retinoic acid metabolism blocking agent (RAMBA). Our objective was to determine the effects of liarozole alone or in combination with tamoxifen on the N-methyl-N-nitrosourea (MNU)-induced rat mammary carcinoma model, as well as on the uterus in ovariectomized immature rats. Methods: (1) Tumor burden experiments: Animals bearing one or more tumors greater than 10 mm in diameter were treated for 56 consecutive days with 20 mg/kg or 80 mg/kg of liarozole by oral gavage, tamoxifen 100 μg/kg by subcutaneous injection, or a combination of liarozole and tamoxifen. At the end of the treatment period, total cumulative tumor volume as well as retinoic acid levels were measured. (2) Uterotrophic assay and proliferation experiments: 21-day-old ovariectomized (OVX) Sprague-Dawley rats were treated with 20 mg/kg or 80 mg/kg of liarozole by oral gavage, tamoxifen 1 mg/kg by subcutaneous injection, and combination of both for 4 consecutive days. At the end of the treatment period, uterine weight, epithelial lining cell height and indices of proliferation cell nuclear antigen (PCNA) were measured. Results: The tumor burden experiments in rats bearing estrogen receptor (ER) positive mammary tumours showed that liarozole has a marked anti-tumour effect. In combination with tamoxifen, liarozole had neither an additive nor an antagonistic effect. However, liarozole markedly reduced the uterotrophic effects induced by tamoxifen. Conclusion: Liarozole's antitumor effects on ER positive mammary tumors and its protective effect on the uterus merit further studies to confirm its clinical value in combination with tamoxifen in ER positive postmenopausal breast cancer. Liarozole and other retinomimetics might also be suitable chemoprevention drugs in combination with tamoxifen because of their favorable toxicity profile

Foot Characteristics of Shod and Unshod Populations

Properly fitted footwear is important for peak athletic performance and comfort (Wakeling, Pascual, & Nigg, 2002; Wunderlich & Cavanagh, 2001). Traditionally, all footwear is designed from a single last that attempts to fit the typical adult male foot (Wunderlich & Cavanagh, 2001). However, it has been found that individuals vary in foot morphology and loading characteristics (Kouchi, 1998; Razeghi & Edward, 2002). The purpose of this study was to document foot characteristics of an unshod population, specifically Samoan, which may aid in footwear design. 116 Samoan individuals and 106 Caucasian individuals were asked to voluntarily participate in the study. Subjects were asked to stand, one foot at a time, in the 3-D scanner as the image was generated. The scanner automatically calculated 7 anthropometric measurements of the foot, including length, breadth, ball girth, instep circumference, height of medial and lateral malleoli, and heel-ankle girth. Not only was the Samoan foot found to be longer and wider than the Caucasian foot, but the shape was also markedly different. It is suggested that Samoan and Caucasian foot dimensions are not comparable when standardized to foot length

The Dynamics of Molecular Material Within 15 pcs of the Galactic Center

We report the results of a 5-field mosaic of the central 15pc of the Galaxy in the (1,1) and (2,2) lines of NH3. Two narrow filaments or streamers are seen running parallel to the Galactic plane. The southern streamer appears to carry gas directly toward the nuclear region from the 20 km/s cloud. The eastern streamer, which we will denote the molecular ridge, appears to be the denser part of the 50 km/s cloud which lies immediately east of the Sgr A East complex and extends in the south towards the 20 km/s cloud. This ridge of gas carries the kinematical signatures of interactions with Sgr A East as well as a SNR which lies south of the Galactic center. The bulk motion of the gas, the enhanced line widths, and the heating of the molecular material all suggest an active evolutionary phase for the gas immediately adjacent to the nucleus.Comment: 11 pages, 13 figures, to appear in The Astrophysical Journa

Vortices in atomic-molecular Bose-Einstein condensates

The structure and stability of vortices in hybrid atomic-molecular Bose-Einstein condensates is analyzed in the framework of a two-component Gross-Pitaevskii-type model that describes the stimulated Raman-induced photoassociation process. New types of topological vortex states are predicted to exist in the coherently coupled two-component condensates even without a trap, and their nontrivial dynamics in the presence of losses is demonstrated.Comment: 7 pages, 6 figure

Eukaryotic initiation factor 4F promotes a reorientation of eukaryotic initiation factor 3 binding on the 5 and the 3 UTRs of barley yellow dwarf virus mRNA

Viral mRNAs that lack a 5 m 7 GTP cap and a 3 poly-A tail rely on structural elements in their untranslated regions (UTRs) to form unique RNA-protein complexes that regulate viral translation. Recent studies of the barley yellow dwarf virus (BYDV) have revealed eukaryotic initiation factor 3 (eIF3) plays a significant role in facilitating communication be- tween its 5 and 3 UTRs by binding both UTRs simultaneously. This report uses in vitro translation assays, fluorescence anisotropy binding assays, and selective 2 -hydroxyl acylation analyzed by primer ex-tension (SHAPE) footprinting to identify secondary structures that are selectively interacting with eIF3. SHAPE data also show that eIF3 alters its interaction with BYDV structures when another factor crucial for BYDV translation, eIF4F, is introduced by the 3 BYDV translational enhancer (BTE). The observed BTE and eIF4F-induced shift of eIF3 position on the 5’ UTR and the translational effects of altering eIF3-binding structures (SLC and SLII) support a new model for BYDV translation initiation that requires the reorientation of eIF3 on BYDV UTRs. This eIF3 function in BYDV translation initiation is both reminiscent of and distinct from eIF3–RNA interactions found in other non-canonically translating mRNAs (e.g. HCV). This characterization of a new role in translation initiation expands the known functionality of eIF3 and may be broadly applicable to other non-canonically translating mRNAs

Molecular Tracers of the Central 12 pc of the Galactic Center

We have used the BIMA array to image the Galactic Center with a 19-pointing mosaic in HCN(1-0), HCO+(1-0), and H 42-alpha emission with 5 km/s velocity resolution and 13'' x 4'' angular resolution. The 5' field includes the circumnuclear ring (CND) and parts of the 20 and 50 km/s clouds. HCN(1-0) and HCO+ trace the CND and nearby giant molecular clouds while the H 42-alpha emission traces the ionized gas in Sgr A West. We find that the CND has a definite outer edge in HCN and HCO+ emission at ~45'' radius and appears to be composed of two or three distinct streams of molecular gas rotating around the nucleus. Outside the CND, HCN and HCO+ trace dense clumps of high-velocity gas in addition to optically thick emission from the 20 and 50 km/s clouds. A molecular ridge of compressed gas and dust, traced in NH3 emission and self-absorbed HCN and HCO+, wraps around the eastern edge of Sgr A East. Just inside this ridge are several arcs of gas which have been accelerated by the impact of Sgr A East with the 50 km/s cloud. HCN and HCO+ emission trace the extension of the northern arm of Sgr A West which appears to be an independent stream of neutral and ionized gas and dust originating outside the CND. Broad line widths and OH maser emission mark the intersection of the northern arm and the CND. Comparison to previous NH3 and 1.2mm dust observations shows that HCN and HCO+ preferentially trace the CND and are weaker tracers of the GMCs than NH3 and dust. We discuss possible scenarios for the emission mechanisms and environment at the Galactic center which could explain the differences in these images.Comment: 24 pages, including 17 figures; to appear in The Astrophysical Journa

Access to care issues adversely affect breast cancer patients in Mexico: oncologists’ perspective

Background: Despite recently implemented access to care programs, Mexican breast cancer (BC) mortality rates remain substantially above those in the US. We conducted a survey among Mexican Oncologists to determine whether practice patterns may be responsible for these differences. Methods: A web-based survey was sent to 851 oncologists across Mexico using the Vanderbilt University REDCap database. Analyses of outcomes are reported using exact and binomial confidence bounds and tests. Results: 138 participants (18.6% of those surveyed) from the National capital and 26 Mexican states, responded. Respondents reported that 58% of newly diagnosed BC patients present with stage III-IV disease; 63% undergo mastectomy, 52% axillary lymph node dissection (ALND) and 48% sentinel lymph node biopsy (SLNB). Chemotherapy is recommended for tumors > 1 cm (89%), positive nodes (86.5%), triple-negative (TN) (80%) and HER2 positive tumors (58%). Trastuzumab is prescribed in 54.3% and 77.5% for HER2 1 cm tumors, respectively. Tamoxifen is indicated for premenopausal hormone receptor (HR) positive tumors in 86.5% of cases and aromatase inhibitors (AI’s) for postmenopausal in 86%. 24% of physicians reported treatment limitations, due to delayed or incomplete pathology reports and delayed or limited access to medications. Conclusions: Even though access to care programs have been recently applied nationwide, women commonly present with advanced BC, leading to increased rates of mastectomy and ALND. Mexican physicians are dissatisfied with access to appropriate medical care. Our survey detects specific barriers that may impact BC outcomes in Mexico and warrant further investigation. Electronic supplementary material The online version of this article (doi:10.1186/1471-2407-14-658) contains supplementary material, which is available to authorized users

E2F1 and p53 Are Dispensable, whereas p21Waf1/Cip1 Cooperates with Rb to Restrict Endoreduplication and Apoptosis during Skeletal Myogenesis

AbstractWe describe temporal and genetic analyses of partially rescued Rb mutant fetuses, mgRb:Rb−/−, that survive to birth and reveal specific defects in skeletal muscle differentiation. We show that in the absence of Rb, these fetuses exhibit increased apoptosis, bona fide endoreduplication, and incomplete differentiation throughout terminal myogenesis. These defects were further augmented in composite mutant fetuses, mgRb:Rb−/−:p21−/−, lacking both Rb and the cyclin-dependent kinase inhibitor p21Waf1/Cip1. Although E2F1 and p53 mediate ectopic DNA synthesis and cell death in several tissues in Rb mutant embryos, both endoreduplication and apoptosis persisted in mgRb:Rb−/−:E2F1−/− and mgRb:Rb−/−:p53−/− compound mutant muscles. Thus, combined inactivation of Rb and p21Waf1/Cip1 augments endoreduplication and apoptosis, whereas E2F1 and p53 are dispensable during aberrant myogenesis in Rb-deficient fetuses