A Reconciliation between the Consumer Price Index and the Personal Consumption Expenditures Price Index

The Bureau of Labor Statistics (BLS) prepares the Consumer Price Index for All Urban Consumers (CPI-U), and the Bureau of Economic Analysis prepares the Personal Consumption Expenditures (PCE) chain-type price index. Both indexes measure the prices paid by consumers for goods and services. Because the two indexes are based on different underlying concepts, they are constructed differently, and tend to behave differently over time. From the first quarter of 2002 through the second quarter of 2007, the CPI-U increased 0.4 percentage point per year faster than the PCE price index. This paper details and quantifies the differences in growth rates between the CPI-U and the PCE price index; it provides a quarterly reconciliation of growth rates for the 2002:Q1- 2007:Q2 time period. There are several factors that explain the differences in growth rates between the CPI and the PCE price index. First, the indexes are based on difference index-number formulas. The CPI-U is based on a Laspeyres index; the PCE price index is based on a Fisher-Ideal index. Second, the relative weights assigned to the detailed item prices in each index are different because they are based on different data sources. The weights used in the CPIU are based on a household survey, while the weights used in the PCE price index are based on business surveys. Third, there are scope differences between the two indexes— that is, there are items in the CPI-U that are out-of-scope of the PCE price index, and there are items in the PCE price index that are out-of-scope of the CPI-U. And finally, there are differences in the seasonal-adjustment routines and in the detailed price indexes used to construct the two indexes. Over the 2002:Q1-2007:Q2 time period, this analysis finds that almost half of the 0.4 percentage point difference in growth rates between the CPI-U and the PCE price index was explained by differences in index-number formulas. After adjusting for formula differences, differences in relative weights—primarily “rent of shelter”—more than accounted for the remaining difference in growth rates. Net scope differences, in contrast, partly offset the effect of relative weight differences.

A molecular biology and phase II trial of lapatinib in children with refractory CNS malignancies: a pediatric brain tumor consortium study.

High expression of ERBB2 has been reported in medulloblastoma and ependymoma; EGFR is amplified and over-expressed in brainstem glioma suggesting these proteins as potential therapeutic targets. We conducted a molecular biology (MB) and phase II study to estimate inhibition of tumor ERBB signaling and sustained responses by lapatinib in children with recurrent CNS malignancies. In the MB study, patients with recurrent medulloblastoma, ependymoma, and high-grade glioma (HGG) undergoing resection were stratified and randomized to pre-resection treatment with lapatinib 900 mg/m(2) dose bid for 7-14 days or no treatment. Western blot analysis of ERBB expression and pathway activity in fresh tumor obtained at surgery estimated ERBB receptor signaling inhibition in vivo. Drug concentration was simultaneously assessed in tumor and plasma. In the phase II study, patients, stratified by histology, received lapatinib continuously, to assess sustained response. Eight patients, on the MB trial (four medulloblastomas, four ependymomas), received a median of two courses (range 1-6+). No intratumoral target inhibition by lapatinib was noted in any patient. Tumor-to-plasma ratios of lapatinib were 10-20 %. In the 34 patients (14 MB, 10 HGG, 10 ependymoma) in the phase II study, lapatinib was well-tolerated at 900 mg/m(2) dose bid. The median number of courses in the phase II trial was two (range 1-12). Seven patients (three medulloblastoma, four ependymoma) remained on therapy for at least four courses range (4-26). Lapatinib was well-tolerated in children with recurrent or CNS malignancies, but did not inhibit target in tumor and had little single agent activity.Fil: Fouladi, Maryam. St. Jude Children’s Research Hospital; Estados UnidosFil: Stewart, Clinton F.. St. Jude Children’s Research Hospital; Estados UnidosFil: Blaney, Susan M.. Baylor College of Medicine. Texas Children’s Cancer Center; Estados UnidosFil: Onar Thomas, Arzu. St. Jude Children’s Research Hospital; Estados UnidosFil: Schaiquevich, Paula Susana. St. Jude Children’s Research Hospital; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Packer, Roger J.. Children’s National Medical Center; Estados UnidosFil: Goldman, Stewart. Anne and Robert H. Lurie Children’s Hospital of Chicago; Estados UnidosFil: Geyer, J. Rusell. Children’s Hospital and Regional Medical Center; Estados UnidosFil: Gajjar, Amar. St. Jude Children’s Research Hospital; Estados UnidosFil: Kun, Larry E.. St. Jude Children’s Research Hospital; Estados UnidosFil: Boyett, James M.. St. Jude Children’s Research Hospital; Estados UnidosFil: Gilbertson, Richard J.. St. Jude Children’s Research Hospital; Estados Unido

Allosteric Regulation of DNA Cleavage and Sequence-Specificity through Run-On Oligomerization

SummarySgrAI is a sequence specific DNA endonuclease that functions through an unusual enzymatic mechanism that is allosterically activated 200- to 500-fold by effector DNA, with a concomitant expansion of its DNA sequence specificity. Using single-particle transmission electron microscopy to reconstruct distinct populations of SgrAI oligomers, we show that in the presence of allosteric, activating DNA, the enzyme forms regular, repeating helical structures characterized by the addition of DNA-binding dimeric SgrAI subunits in a run-on manner. We also present the structure of oligomeric SgrAI at 8.6 Å resolution, demonstrating the conformational state of SgrAI in its activated form. Activated and oligomeric SgrAI displays key protein-protein interactions near the helix axis between its N termini, as well as allosteric protein-DNA interactions that are required for enzymatic activation. The hybrid approach reveals an unusual mechanism of enzyme activation that explains SgrAI’s oligomerization and allosteric behavior

Non-imaging method: 3D scanning.

Three-dimensional body scanning is used to determine surface anthropometry characteristics such as body volume, segment lengths and girths. Three-dimensional scanning systems use laser, light or infrared technologies to acquire shape and software to allow manual or automatically extracted measures. Body posture during scanning is important to ensure accurate measures can be made from the images. The image vary depending on the configuration, resolution and accuracy of the scanner

P-glycoprotein, but not multidrug resistance protein 4, plays a role in the systemic clearance of irinotecan and SN-38 in mice

The ATP-binding cassette transporters P-glycoprotein (ABCB1, MDR1) and multidrug resistance protein 4 (MRP4) efflux irinotecan and its active metabolite SN-38 in vitro, and thus may contribute to system clearance of these compounds. Mdr1a/b(-/-), Mrp4(-/-), and wild-type mice were administered 20 or 40 mg/kg irinotecan, and plasma samples were collected for 6 hours. Irinotecan and SN-38 lactone and carboxylate were quantitated and data were analyzed with nonlinear mixed-effects modeling. Mdr1a/b genotype was a significant covariate for the clearance of both irinotecan lactone and SN-38 lactone. Exposures to irinotecan lactone and SN-38 lactone after a 40 mg/kg dose were 1.6-fold higher in Mdr1a/b(-/-) mice compared to wild-type mice. Plasma concentrations of irinotecan lactone, irinotecan carboxylate, and SN-38 lactone in Mrp4(-/-) mice were similar to the wild-type controls. These results suggest that P-gp plays a role in irinotecan and SN-38 elimination, but Mrp4 does not affect irinotecan or SN-38 plasma pharmacokinetics.Fil: Tagen, Michael. St. Jude Children's Research Hospital; Estados UnidosFil: Zhuang, Yanli. St. Jude Children's Research Hospital; Estados UnidosFil: Zhang, Fan. St. Jude Children's Research Hospital; Estados UnidosFil: Harstead, K. Elaine. St. Jude Children's Research Hospital; Estados UnidosFil: Shen, Jun. St. Jude Children's Research Hospital; Estados UnidosFil: Schaiquevich, Paula Susana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. St. Jude Children's Research Hospital; Estados UnidosFil: Fraga, Charles H.. St. Jude Children's Research Hospital; Estados UnidosFil: Panetta, John C.. St. Jude Children's Research Hospital; Estados UnidosFil: Waters, Christopher M.. St. Jude Children's Research Hospital; Estados UnidosFil: Stewart, Clinton F.. St. Jude Children's Research Hospital; Estados Unido

Understory 2014

“Art is the struggle to be, in a particular sort of way, virtuous.” —Iris Murdoch Indeed, when we embark on any creative adventure it is with the purpose of conveying a certain truth; an emotion, an idea that brings us together and reminds us of the innate consciousness that dwells within. Understory is emblematic of this; where individuals intent on honing their craft can join others to become a part of something greater, their work immortalized to become a time capsule. Decades from now a volume of Understory may be discovered on a dusty bookshelf in some forgotten corner and the lucky explorer who finds it shall be enlightened by pages of gold. We, as editors of Understory 2014, have worked very hard this year to put together a journal that showcases the very best of the University of Alaska Anchorage undergraduate student work. We hope you enjoy your journey through this issue as much as we have enjoyed ours. Thank you to the English and Art Departments, for the staff and faculty’s unerring support of our club; to Provost Baker, for seeing and believing in the vision of Understory; and to our club’s faculty advisor, Douglass Bourne, for his guidance and tireless assistance. Finally, thank you to the wonderful students who submit such excellent work each year. Without your passion for the arts, we would not be here.Staff / Letter from the Editors / Glass Blower / Writing / Obsolete Evolution / Permafrost / Phoenix / Untitled / Ratio / Tripping / Abiogenesis / My Heart Beats for You / Meeting of the Fingerprint Lines / You Are No Stranger / Nightmare Fuel / Cane-Sugar / Gossamer Strands / Panthera Gold / Butterfly / A Mantis Too Far / Long and Winding Road / Chasing Shadows / Merisunas / Chequer Grove / Modzilla / Beans / Little Red and Mr. Wolf / In Memoriam, Joel Fletcher Armstrong / Glance / Courage / Uranium Waltz / Danger / Journey to the West / Antumbra / Roaring Like a Lion / Pre-boarding / Untitled / How Do You Say a Word / Fishing for Doom/ Contributor

Preclinical studies of 5-fluoro-2'-deoxycytidine and tetrahydrouridine in pediatric brain tumors.

Chemotherapies active in preclinical studies frequently fail in the clinic due to lack of efficacy, which limits progress for rare cancers since only small numbers of patients are available for clinical trials. Thus, a preclinical drug development pipeline was developed to prioritize potentially active regimens for pediatric brain tumors spanning from in vitro drug screening, through intracranial and intra-tumoral pharmacokinetics to in vivo efficacy studies. Here, as an example of the pipeline, data are presented for the combination of 5-fluoro-2'-deoxycytidine and tetrahydrouridine in three pediatric brain tumor models. The in vitro activity of nine novel therapies was tested against tumor spheres derived from faithful mouse models of Group 3 medulloblastoma, ependymoma, and choroid plexus carcinoma. Agents with the greatest in vitro potency were then subjected to a comprehensive series of in vivo pharmacokinetic (PK) and pharmacodynamic (PD) studies culminating in preclinical efficacy trials in mice harboring brain tumors. The nucleoside analog 5-fluoro-2'-deoxycytidine (FdCyd) markedly reduced the proliferation in vitro of all three brain tumor cell types at nanomolar concentrations. Detailed intracranial PK studies confirmed that systemically administered FdCyd exceeded concentrations in brain tumors necessary to inhibit tumor cell proliferation, but no tumor displayed a significant in vivo therapeutic response. Despite promising in vitro activity and in vivo PK properties, FdCyd is unlikely to be an effective treatment of pediatric brain tumors, and therefore was deprioritized for the clinic. Our comprehensive and integrated preclinical drug development pipeline should reduce the attrition of drugs in clinical trials

Review of microdialysis in brain tumors, from concept to application: First Annual Carolyn Frye-Halloran Symposium

In individuals with brain tumors, pharmacodynamic and pharmacokinetic studies of therapeutic agents have historically used analyses of drug concentrations in serum or cerebrospinal fluid, which unfortunately do not necessarily reflect concentrations within the tumor and adjacent brain. This review article introduces to neurological and medical oncologists, as well as pharmacologists, the application of microdialysis in monitoring drug metabolism and delivery within the fluid of the interstitial space of brain tumor and its surroundings. Microdialysis samples soluble molecules from the extracellular fluid via a semipermeable membrane at the tip of a probe. In the past decade, it has been used predominantly in neurointensive care in the setting of brain trauma, vasospasm, epilepsy, and intracerebral hemorrhage. At the first Carolyn Frye-Halloran Symposium held at Massachusetts General Hospital in March 2002, the concept of microdialysis was extended to specifically address its possible use in treating brain tumor patients. In doing so we provide a rationale for the use of this technology by a National Cancer Institute consortium, New Approaches to Brain Tumor Therapy, to measure levels of drugs in brain tissue as part of phase 1 trials. Originally published Neuro-oncology, Vol. 6, No. 1, Jan 200