332 research outputs found
Toward Enhancing the Quality and Quantity of Marketing Majors
This article reports the findings of a survey of undergraduate
students designed to examine the key factors involved in
selecting a marketing major. A discussion follows, dealing
with the initiatives undertaken by marketing departments at
various universities in an attempt to enhance the quality and
quantity of marketing majors.Statistics Working Papers Serie
Neoamphimedine Circumvents Metnase-Enhanced DNA Topoisomerase IIα Activity Through ATP-Competitive Inhibition
Type IIα DNA topoisomerase (TopoIIα) is among the most important clinical drug targets for the treatment of cancer. Recently, the DNA repair protein Metnase was shown to enhance TopoIIα activity and increase resistance to TopoIIα poisons. Using in vitro DNA decatenation assays we show that neoamphimedine potently inhibits TopoIIα-dependent DNA decatenation in the presence of Metnase. Cell proliferation assays demonstrate that neoamphimedine can inhibit Metnase-enhanced cell growth with an IC50 of 0.5 μM. Additionally, we find that the apparent Km of TopoIIα for ATP increases linearly with higher concentrations of neoamphimedine, indicating ATP-competitive inhibition, which is substantiated by molecular modeling. These findings support the continued development of neoamphimedine as an anticancer agent, particularly in solid tumors that over-express Metnase
A phase 1b randomized clinical trial of CT1812 to measure Aβ oligomer displacement in Alzheimer’s disease using an indwelling CSF catheter
Universal scaling in the branching of the Tree of Life
Understanding the patterns and processes of diversification of life in the
planet is a key challenge of science. The Tree of Life represents such
diversification processes through the evolutionary relationships among the
different taxa, and can be extended down to intra-specific relationships. Here
we examine the topological properties of a large set of interspecific and
intraspecific phylogenies and show that the branching patterns follow
allometric rules conserved across the different levels in the Tree of Life, all
significantly departing from those expected from the standard null models. The
finding of non-random universal patterns of phylogenetic differentiation
suggests that similar evolutionary forces drive diversification across the
broad range of scales, from macro-evolutionary to micro-evolutionary processes,
shaping the diversity of life on the planet.Comment: 6 pages + 19 of Supporting Informatio
New Role, New Country: introducing US physician assistants to Scotland
This paper draws from research commissioned by the Scottish Executive Health Department (SEHD). It provides a case study in the introduction of a new health care worker role into an already well established and "mature" workforce configuration It assesses the role of US style physician assistants (PAs), as a precursor to planned "piloting" of the PA role within the National Health Service (NHS) in Scotland
Recruitment Constraints in Singapore's Fluted Giant Clam (Tridacna squamosa) Populations - A Dispersal Model Approach
10.1371/journal.pone.0058819PLoS ONE83
Wall shear stress as measured in vivo: consequences for the design of the arterial system
Based upon theory, wall shear stress (WSS), an important determinant of endothelial function and gene expression, has been assumed to be constant along the arterial tree and the same in a particular artery across species. In vivo measurements of WSS, however, have shown that these assumptions are far from valid. In this survey we will discuss the assessment of WSS in the arterial system in vivo and present the results obtained in large arteries and arterioles. In vivo WSS can be estimated from wall shear rate, as derived from non-invasively recorded velocity profiles, and whole blood viscosity in large arteries and plasma viscosity in arterioles, avoiding theoretical assumptions. In large arteries velocity profiles can be recorded by means of a specially designed ultrasound system and in arterioles via optical techniques using fluorescent flow velocity tracers. It is shown that in humans mean WSS is substantially higher in the carotid artery (1.1–1.3 Pa) than in the brachial (0.4–0.5 Pa) and femoral (0.3–0.5 Pa) arteries. Also in animals mean WSS varies substantially along the arterial tree. Mean WSS in arterioles varies between about 1.0 and 5.0 Pa in the various studies and is dependent on the site of measurement in these vessels. Across species mean WSS in a particular artery decreases linearly with body mass, e.g., in the infra-renal aorta from 8.8 Pa in mice to 0.5 Pa in humans. The observation that mean WSS is far from constant along the arterial tree implies that Murray’s cube law on flow-diameter relations cannot be applied to the whole arterial system. Because blood flow velocity is not constant along the arterial tree either, a square law also does not hold. The exponent in the power law likely varies along the arterial system, probably from 2 in large arteries near the heart to 3 in arterioles. The in vivo findings also imply that in in vitro studies no average shear stress value can be taken to study effects on endothelial cells derived from different vascular areas or from the same artery in different species. The cells have to be studied under the shear stress conditions they are exposed to in real life
Engineered Models of Metastasis with Application to Study Cancer Biomechanics
Three-dimensional complex biomechanical interactions occur from the initial steps of tumor formation to the later phases of cancer metastasis. Conventional monolayer cultures cannot recapitulate the complex microenvironment and chemical and mechanical cues that tumor cells experience during their metastatic journey, nor the complexity of their interactions with other, noncancerous cells. As alternative approaches, various engineered models have been developed to recapitulate specific features of each step of metastasis with tunable microenvironments to test a variety of mechanistic hypotheses. Here the main recent advances in the technologies that provide deeper insight into the process of cancer dissemination are discussed, with an emphasis on three-dimensional and mechanical factors as well as interactions between multiple cell types
Premature ovarian failure and ovarian autoimmunity
Premature ovarian failure (POF) is defined as a syndrome characterized by
menopause before the age of 40 yr. The patients suffer from anovulation
and hypoestrogenism. Approximately 1% of women will experience menopause
before the age of 40 yr. POF is a heterogeneous disorder with a
multicausal pathogenesis involving chromosomal, genetic, enzymatic,
infectious, and iatrogenic causes. There remains, however, a group of POF
patients without a known etiology, the so-called "idiopathic" form. An
autoimmune etiology is hypothesized for the POF cases with a concomitant
Addison's disease and/or oophoritis. It is concluded in this review that
POF in association with adrenal autoimmunity and/or Addison's disease
(2-10% of the idiopathic POF patients) is indeed an autoimmune disease.
The following evidence warrants this view: 1) The presence of
autoantibodies to steroid-producing cells in these patients; 2) The
characterization of shared autoantigens between adrenal and ovarian
steroid-producing cells; 3) The histological picture of the ovaries of
such cases (lymphoplasmacellular infiltrate around steroid-producing
cells); 4) The existence of various autoimmune animal models for this
syndrome, which underlines the autoimmune nature of the disease. There is
some circumstantial evidence for an autoimmune pathogenesis in idiopathic
POF patients in the absence of adrenal autoimmunity or Addison's disease.
Arguments in support of this are: 1) The presence of cellular immune
abnormalities in this POF patient group reminiscent of endocrine
autoimmune diseases such as IDDM, Graves' disease, and Addison's disease;
2) The more than normal association with IDDM and myasthenia gravis. Data
on the presence of various ovarian autoantibodies and anti-receptor
antibodies in these patients are, however, inconclusive and need further
evaluation. A strong argument against an autoimmune pathogenesis of POF in
these patients is the nearly absent histological confirmation (the
presence of an oophoritis) in these cases (< 3%). However, in animal
models using ZP immunization, similar follicular depletion and fibrosis
(as in the POF women) can be detected. Accepting the concept that POF is a
heterogenous disorder in which some of the idiopathic forms are based on
an abnormal self-recognition by th
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