6,442 research outputs found
The topology of deformation spaces of Kleinian groups
Let M be a compact, hyperbolizable 3-manifold with nonempty incompressible
boundary and let AH(\pi_1(M)) denote the space of (conjugacy classes of)
discrete faithful representations of \pi_1(M) into PSL 2 (C). The components of
the interior MP(\pi_1(M)) of AH(\pi_1(M)) (as a subset of the appropriate
representation variety) are enumerated by the space A(M) of marked
homeomorphism types of oriented, compact, irreducible 3-manifolds homotopy
equivalent to M. In this paper, we give a topological enumeration of the
components of the closure of MP(\pi_1(M)) and hence a conjectural topological
enumeration of the components of AH(\pi_1(M)). We do so by characterizing
exactly which changes of marked homeomorphism type can occur in the algebraic
limit of a sequence of isomorphic freely indecomposable Kleinian groups. We use
this enumeration to exhibit manifolds M for which AH(\pi_1(M)) has infinitely
many components.Comment: 49 pages, published versio
Effects of Nitrogen Fertilization on Monoterpenes of Jack Pine Seedlings and Weight Gain of Jack Pine Budworm (Lepidoptera: Tortricidae)
Nine-month old jack pine (Pinus banksiana) seedlings were grown in a greenhouse under four nitrogen fertilization regimes. Levels of total nitrogen and five monoterpenes in new foliage were measured. Fertilization resulted in four significantly different levels of foliar nitrogen; means ranged from 1.8-4.5 percent dry weight. Contrary to predictions of resource availability theory, seedlings grown under the highest fertilization regime had higher foliar monoterpene levels than seedlings in the other treatments. Newly molted, sixth-instar female jack pine budworm (Choristoneura pinus pinus [Lepidoptera: Tortricidae]) larvae were allowed to feed for four days on new foliage of the seedlings. Larvae that fed on low-nitrogen seedling gained less weight and process more vegetation than did larvae on high- nitrogen seedlings. Larval weight gain was positively related to foliar nitrogen
Cybershopping Levels The Playing Field In Global Retailing
Today\u27s business environment has an ever-changing landscape. The environment is no longer just local, regional, or national. It is a global environment. The most successful businesses will have to be able to meet the needs of its customers before its competitors. Many people do not like huge stores and crowded aisles. Also, the element of customer service seems to be vanishing. This has led to customer dissatisfaction. Customers are increasingly looking for a new format in which they can buy their goods. They have increasingly turned to the Internet. The future of the Internet looks bright. Retailers are making their home pages user friendly and consumers are gaining more confidence and becoming more computer literate
Exhibits and Demonstrations for Junior Farm Management Clubs
The State Fair Board offers attractive cash premiums for exhibits made by members of Fa.rm Ma1:1agement Clubs. These exhibits consist of two sketches of the member\u27s farm showing location and arrangement of fields and buildings and a copy of their account book with entries complete to August 15 or later. One sketch should picture the farm as it is now and the other as it would appear after any changes had been made. These sketches should be on cardboard 11 by 22 inches or 22 by 28 inches in size. Additional account books will be furnished by the Extension Service to members desiring to exhibit at the State Fair. These books will be numbered so that members need not put their names on their exhibits
The role of data & program code archives in the future of economic research
This essay examines the role of data and program-code archives in making economic research "replicable." Replication of published results is recognized as an essential part of the scientific method. Yet, historically, both the "demand for" and "supply of" replicable results in economics has been minimal. "Respect for the scientific method" is not sufficient to motivate either economists or editors of professional journals to ensure the replicability of published results. We enumerate the costs and benefits of mandatory data and code archives, and argue that the benefits far exceed the costs. Progress has been made since the gloomy assessment of Dewald, Thursby and Anderson some twenty years ago in the American Economic Review, but much remains to be done before empirical economics ceases to be a "dismal science" when judged by the replicability of its published results.Econometrics ; Research
Determination and Reduction of Large Diffeomorphisms
Within the Hamiltonian formulation of diffeomorphism invariant theories we
address the problem of how to determine and how to reduce diffeomorphisms
outside the identity component.Comment: 4 pages, Latex, macro espcrc2.sty. Contribution to the proceedings of
the second conference on Constrained Dynamics and Quantum Gravity, Santa
Margherita, Italy, 17-21 September 1996. To appear in Nucl. Phys. B Supp
Purified venom components inhibit EGFR phosphorylation in triple negative breast cancer
Abstract: EACR22-0963
Introduction
Breast cancer remains the most commonly diagnosed type of cancer in both menopausal age women and adolescent/young adults. 10-20% of diagnosed breast cancers are deemed to be triple negative (TN), lacking expression of hormone receptors and HER2. Triple negative breast cancers (TNBC) present with poor patient prognosis, through their lack of effective treatment options. Studies report that epidermal growth factor receptor (EGFR) is expressed in 15–45% of all breast tumours and its expression is inversely related to hormone receptor expression. Expression of EGFR is indicative of poor prognosis, making it an attractive target for treatment in both TN and receptor expressing cancer subtypes. Development of resistance to current EGFR targeted therapeutics is common, leading to treatment failure and patient relapse, thus novel compound classes are needed. Venom peptides have evolved to be secreted into the lumen of the venom gland and stored ready for rapid delivery; therefore they are exceptionally stable. These proteins naturally act as ligands for a large variety of receptors and ion channels, making them a rich source of potentially novel drug like molecules.
Material and Methods
In this study the Venomtech Targeted-Venom Discovery ArrayEGFR (T-VDA™) containing 320 venom 2D HPLC fractions was screened using Abcam Human EGFR (pY1086) + total EGFR ELISA Kits to identify venom peptides with antagonistic activity against EGFR pY1086 phosphorylation. Optimal cell number, dosing and lysate concentrations were determined empirically. MDA-MB-468 TNBC cells were dosed at 20ug/ml for 2h with fractions, before being stimulated with 1x10-7M EGF for 5 mins. Further assay protocol was carried out as per manufacturer’s instructions. TMB Absorbance signal was measured using a CLARIOstarPLUS plate reader at 450nm (BMG LabTech).
Results and Discussions
Screening of the TVDAEGFR array (N=2) identified 7 hit fractions (2.2% hit rate) from the venoms of three distinct rattlesnake genera from Northern, Central and southern America, and 1 viper species from Northern Africa. These fractions were followed up with dose response, mass spec and drug like properties.
Conclusion
Purified protein components from the venoms of pit vipers and vipers show the capacity to antagonistically inhibit the phosphorylation of EGFR at specific tyrosine residues linked to downstream signalling pathways in TNBC cells. Thus, representing a novel chemical class for targeting EGF
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