178 research outputs found
How Much is Enough? The "Ballot Order Effect" and the use of Social Science Research in Election Law Disputes
Previous empirical research and other related research from survey methodology holds that candidates listed ļ¬rst on an election ballot may gain some measure of advantage from this ballot placement. Using data from the 1998 general election in California, we test whether a candidateās relative position on the ballot has any statistical effect on vote shares. We ļ¬nd little systematic evidence that candidate vote shares beneļ¬t from being listed ļ¬rst on the ballot. We show that there is not a primacy ballot order effect (deļ¬ned as being listed ļ¬rst on the ballot) in every contest, that when the effect exists it is often very small, and that the effect is evenly distributed between primacy and latency (deļ¬ned as being listed last on the ballot). We consider how courts should balance the concern over ballot order effect against other interests, such as the costs and potential confusion associated with rotation and randomization
Excitons in T-shaped quantum wires
We calculate energies, oscillator strengths for radiative recombination, and
two-particle wave functions for the ground state exciton and around 100 excited
states in a T-shaped quantum wire. We include the single-particle potential and
the Coulomb interaction between the electron and hole on an equal footing, and
perform exact diagonalisation of the two-particle problem within a finite basis
set. We calculate spectra for all of the experimentally studied cases of
T-shaped wires including symmetric and asymmetric GaAs/AlGaAs and
InGaAs/AlGaAs structures. We study in detail the
shape of the wave functions to gain insight into the nature of the various
states for selected symmetric and asymmetric wires in which laser emission has
been experimentally observed. We also calculate the binding energy of the
ground state exciton and the confinement energy of the 1D quantum-wire-exciton
state with respect to the 2D quantum-well exciton for a wide range of
structures, varying the well width and the Al molar fraction . We find that
the largest binding energy of any wire constructed to date is 16.5 meV. We also
notice that in asymmetric structures, the confinement energy is enhanced with
respect to the symmetric forms with comparable parameters but the binding
energy of the exciton is then lower than in the symmetric structures. For
GaAs/AlGaAs wires we obtain an upper limit for the binding energy
of around 25 meV in a 10 {\AA} wide GaAs/AlAs structure which suggests that
other materials must be explored in order to achieve room temperature
applications. There are some indications that
InGaAs/AlGaAs might be a good candidate.Comment: 20 pages, 10 figures, uses RevTeX and psfig, submitted to Physical
Review
On the stability of 2 \sqrt{2} x 2 \sqrt{2} oxygen ordered superstructures in YBa2Cu3O6+x
We have compared the ground-state energy of several observed or proposed " 2
\sqrt{2} x 2 \sqrt{2} oxygen (O) ordered superstructures " (from now on HS),
with those of "chain superstructures" (CS) (in which the O atoms of the basal
plane are ordered in chains), for different compositions x in YBa2Cu3O6+x. The
model Hamiltonian contains i) the Madelung energy, ii) a term linear in the
difference between Cu and O hole occupancies which controls charge transfer,
and iii) covalency effects based on known results for models in one and
two dimensions. The optimum distribution of charge is determined minimizing the
total energy, and depends on two parameters which are determined from known
results for x=1 and x=0.5. We obtain that on the O lean side, only CS are
stable, while for x=7/8, a HS with regularly spaced O vacancies added to the
x=1 structure is more stable than the corresponding CS for the same x. We find
that the detailed positions of the atoms in the structure, and long-range
Coulomb interactions, are crucial for the electronic structure, the mechanism
of charge transfer, the stability of the different phases, and the possibility
of phase separation.Comment: 24 text pages, Latex, one fig. included as ps file, to be publisheb
in Phys. Rev.
New development: Running elections during a pandemic
The Covid-19 pandemic posed a profound challenge for the delivery of elections worldwide. Elections are indispensable for democracy, but the high volume of human interactions within the electoral process risked spreading the virus. Electoral officials therefore found themselves planning or managing an election during an emergency situation, often for the first time. This article argues that there are several major organizational āelephant trapsā that polities will need to side-step during pandemics in order to safely protect the healthy running of elections. IMPACT: Elections often take place in during emergency situations such as pandemics, floods, earthquakes and hurricanes. In order to secure electoral integrity, this article encourages governments, legislators and electoral management bodies to: build political consensuses, consider the impact on the whole electoral cycle, include a wide range of stakeholders in meetings, invest in sufficient resources, undertake risk assessments and avoid late major changes to electoral law
PET Imaging of Microglia Using PBR28suv Determines Therapeutic Efficacy of Autologous Bone Marrow Mononuclear Cells Therapy in Traumatic Brain Injury
Traumatic brain injury (TBI) results in activated microglia. Activated microglia can be measured in vivo by using positron emission topography (PET) ligand peripheral benzodiazepine receptor standardized uptake values (PBR28suv). Cell based therapies have utilized autologous bone marrow mononuclear cells (BMMNCs) to attenuate activated microglia after TBI. This study aims to utilize in vivo PBR28suv to assess the efficacy of BMMNCs therapy after TBI. Seventy-two hours after CCI injury, BMMNCs were harvested from the tibia and injected via tail-vein at 74 h after injury at a concentration of 2 million cells per kilogram of body weight. There were three groups of rats: Sham, CCI-alone and CCI-BMMNCs (AUTO). One hundred twenty days after injury, rodents were imaged with PBR28 and their cognitive behavior assessed utilizing the Morris Water Maze. Subsequent ex vivo analysis included brain volume and immunohistochemistry. BMMNCs therapy attenuated PBR28suv in comparison to CCI alone and it improved spatial learning as measured by the Morris Water Maze. Ex vivo analysis demonstrated preservation of brain volume, a decrease in amoeboid-shaped microglia in the dentate gyrus and an increase in the ratio of ramified to amoeboid microglia in the thalamus. PBR28suv is a viable option to measure efficacy of BMMNCs therapy after TBI
p53 modeling as a route to mesothelioma patients stratification and novel therapeutic identification
Background
Malignant pleural mesothelioma (MPM) is an orphan disease that is difficult to treat using traditional chemotherapy, an approach which has been effective in other types of cancer. Most chemotherapeutics cause DNA damage leading to cell death. Recent discoveries have highlighted a potential role for the p53 tumor suppressor in this disease. Given the pivotal role of p53 in the DNA damage response, here we investigated the predictive power of the p53 interactome model for MPM patientsā stratification.
Methods
We used bioinformatics approaches including omics type analysis of data from MPM cells and from MPM patients in order to predict which pathways are crucial for patientsā survival. Analysis of the PKT206 model of the p53 network was validated by microarrays from the Mero-14 MPM cell line and RNA-seq data from 71 MPM patients, whilst statistical analysis was used to identify the deregulated pathways and predict therapeutic schemes by linking the affected pathway with the patientsā clinical state.
Results
In silico simulations demonstrated successful predictions ranging from 52 to 85% depending on the drug, algorithm or sample used for validation. Clinical outcomes of individual patients stratified in three groups and simulation comparisons identified 30 genes that correlated with survival. In patients carrying wild-type p53 either treated or not treated with chemotherapy, FEN1 and MMP2 exhibited the highest inverse correlation, whereas in untreated patients bearing mutated p53, SIAH1 negatively correlated with survival. Numerous repositioned and experimental drugs targeting FEN1 and MMP2 were identified and selected drugs tested. Epinephrine and myricetin, which target FEN1, have shown cytotoxic effect on Mero-14 cells whereas marimastat and batimastat, which target MMP2 demonstrated a modest but significant inhibitory effect on MPM cell migration. Finally, 8 genes displayed correlation with disease stage, which may have diagnostic implications.
Conclusions
Clinical decisions related to MPM personalized therapy based on individual patientsā genetic profile and previous chemotherapeutic treatment could be reached using computational tools and the predictions reported in this study upon further testing in animal models
Maternal Behavior is Impaired in Female Mice Lacking Type 3 Adenylyl Cyclase
Although chemosensory signals generated by mouse pups may trigger maternal behavior of females, the mechanism for detection of these signals has not been fully defined. As some odorant receptors are coupled to the type 3 adenylyl cyclase (AC3), we evaluated the role of AC3 for maternal behavior using AC3ā/ā female mice. Here, we report that maternal behavior is impaired in virgin and postpartum AC3ā/ā mice. Female AC3ā/ā mice failed the pup retrieval assay, did not construct well-defined nests, and did not exhibit maternal aggression. Furthermore, AC3ā/ā females could not detect odorants or pup urine in the odorant habituation test and were unable to detect pups by chemoreception. In contrast to wild-type mice, AC activity in main olfactory epithelium (MOE) preparations from AC3ā/ā female mice was not stimulated by odorants or pheromones. Moreover, odorants and pheromones did not evoke electro-olfactogram (EOG) responses in the MOE of AC3ā/ā female mice. We hypothesize that the detection of chemical signals that trigger maternal behavior in female mice depends upon AC3 in the MOE
Stress and breast cancer: from epidemiology to molecular biology
Stress exposure has been proposed to contribute to the etiology of breast cancer. However, the validity of this assertion and the possible mechanisms involved are not well established. Epidemiologic studies differ in their assessment of the relative contribution of stress to breast cancer risk, while physiological studies propose a clear connection but lack the knowledge of intracellular pathways involved. The present review aims to consolidate the findings from different fields of research (including epidemiology, physiology, and molecular biology) in order to present a comprehensive picture of what we know to date about the role of stress in breast cancer development
Prolactin-induced mouse mammary carcinomas model estrogen resistant luminal breast cancer.
INTRODUCTION: Tumors that express estrogen receptor alpha (ERĪ±+) comprise 75% of breast cancers in women. While treatments directed against this receptor have successfully lowered mortality rates, many primary tumors initially or later exhibit resistance. The paucity of murine models of this luminal tumor subtype has hindered studies of factors that promote their pathogenesis and modulate responsiveness to estrogen-directed therapeutics. Since epidemiologic studies closely link prolactin and the development of ERĪ±+ tumors in women, we examined characteristics of the aggressive ERĪ±+ and ERĪ±- carcinomas which develop in response to mammary prolactin in a murine transgenic model (neu-related lipocalin- prolactin (NRL-PRL)). To evaluate their relationship to clinical tumors, we determined phenotypic relationships among these carcinomas, other murine models of breast cancer, and features of luminal tumors in women.
METHODS: We examined a panel of prolactin-induced tumors for characteristics relevant to clinical tumors: histotype, ERĪ±/progesterone receptor (PR) expression and estrogen responsiveness, Activating Protein 1 (AP-1) components, and phosphorylation of signal transducer and activator of transcription 5 (Stat5), extracellular signal regulated kinase (ERK) 1/2 and AKT. We compared levels of transcripts in the ERĪ±-associated luminal signature that defines this subtype of tumors in women and transcripts enriched in various mammary epithelial lineages to other well-studied genetically modified murine models of breast cancer. Finally, we used microarray analyses to compare prolactin-induced ERĪ±+ and ERĪ±- tumors, and examined responsiveness to estrogen and the anti-estrogen, Faslodex, in vivo.
RESULTS: Prolactin-induced carcinomas were markedly diverse with respect to histotype, ERĪ±/PR expression, and activated signaling cascades. They constituted a heterogeneous, but distinct group of murine mammary tumors, with molecular features of the luminal subtype of human breast cancer. In contrast to morphologically normal and hyperplastic structures in NRL-PRL females, carcinomas were insensitive to ERĪ±-mediated signals. These tumors were distinct from mouse mammary tumor virus (MMTV)-neu tumors, and contained elevated transcripts for factors associated with luminal/alveolar expansion and differentiation, suggesting that they arose from physiologic targets of prolactin. These features were shared by ERĪ±+ and ERĪ±- tumors, suggesting a common origin, although the former exhibited transcript profiles reflecting greater differentiation.
CONCLUSIONS: Our studies demonstrate that prolactin can promote diverse carcinomas in mice, many of which resemble luminal breast cancers, providing a novel experimental model to examine the pathogenesis, progression and treatment responsiveness of this tumor subtype
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