The asymptotic relative efficiency of mixed statistical tests

Mixed statistical tests are described. It is shown that these tests have a much higher efficiency than conventionally used statistics such as the sign test and polarity coincidence correlation without the high operational complexity of the Wilcoxon, Mann-Whitney, Kendall\tau, or Fisher-Yates: Terry-Hoeffding tests

Attosecond double-slit experiment

A new scheme for a double-slit experiment in the time domain is presented. Phase-stabilized few-cycle laser pulses open one to two windows (``slits'') of attosecond duration for photoionization. Fringes in the angle-resolved energy spectrum of varying visibility depending on the degree of which-way information are observed. A situation in which one and the same electron encounters a single and a double slit at the same time is discussed. The investigation of the fringes makes possible interferometry on the attosecond time scale. The number of visible fringes, for example, indicates that the slits are extended over about 500as.Comment: 4 figure

A Synergistic Antiproliferation Effect of Curcumin and Docosahexaenoic Acid in SK-BR-3 Breast Cancer Cells: Unique Signaling Not Explained by the Effects of Either Compound Alone.

Background Breast cancer is a collection of diseases in which molecular phenotypes can act as both indicators and mediators of therapeutic strategy. Therefore, candidate therapeutics must be assessed in the context of multiple cell lines with known molecular phenotypes. Docosahexaenoic acid (DHA) and curcumin (CCM) are dietary compounds known to antagonize breast cancer cell proliferation. We report that these compounds in combination exert a variable antiproliferative effect across multiple breast cell lines, which is synergistic in SK-BR-3 cells and triggers cell signaling events not predicted by the activity of either compound alone. Methods Dose response curves for CCM and DHA were generated for five breast cell lines. Effects of the DHA+ CCM combination on cell proliferation were evaluated using varying concentrations, at a fixed ratio, of CCM and DHA based on their individual ED50. Detection of synergy was performed using nonlinear regression of a sigmoid dose response model and Combination Index approaches. Cell molecular network responses were investigated through whole genome microarray analysis of transcript level changes. Gene expression results were validated by RT-PCR, and western blot analysis was performed for potential signaling mediators. Cellular curcumin uptake, with and without DHA, was analyzed via flow cytometry and HPLC. Results CCM+DHA had an antiproliferative effect in SK-BR-3, MDA-MB-231, MDA-MB-361, MCF7 and MCF10AT cells. The effect was synergistic for SK-BR-3 (ER- PR- Her2+) relative to the two compounds individually. A whole genome microarray approach was used to investigate changes in gene expression for the synergistic effects of CCM+DHA in SK-BR-3 cells lines. CCM+DHA triggered transcript-level responses, in disease-relevant functional categories, that were largely non-overlapping with changes caused by CCM or DHA individually. Genes involved in cell cycle arrest, apoptosis, inhibition of metastasis, and cell adhesion were upregulated, whereas genes involved in cancer development and progression, metastasis, and cell cycle progression were downregulated. Cellular pools of PPARγ and phospho-p53 were increased by CCM+DHA relative to either compound alone. DHA enhanced cellular uptake of CCM in SK-BR-3 cells without significantly enhancing CCM uptake in other cell lines. Conclusions The combination of DHA and CCM is potentially a dietary supplemental treatment for some breast cancers, likely dependent upon molecular phenotype. DHA enhancement of cellular curcumin uptake is one potential mechanism for observed synergy in SK-BR-3 cells; however, transcriptomic data show that the antiproliferation synergy accompanies many signaling events unique to the combined presence of the two compounds

The Locality Problem in Quantum Measurements

The locality problem of quantum measurements is considered in the framework of the algebraic approach. It is shown that contrary to the currently widespread opinion one can reconcile the mathematical formalism of the quantum theory with the assumption of the existence of a local physical reality determining the results of local measurements. The key quantum experiments: double-slit experiment on electron scattering, Wheeler's delayed-choice experiment, the Einstein-Podolsky-Rosen paradox, and quantum teleportation are discussed from the locality-problem point of view. A clear physical interpretation for these experiments, which does not contradict the classical ideas, is given.Comment: Latex, 40 pages, 7 figure

Addressing the unmet clinical need for low-volume assays in early diagnosis of pancreatic cancer

The incidental detection of pancreatic cysts, an opportunity for the early detection of pancreatic cancer, is increasing, owing to an aging population and improvements in imaging technology. The classification of pancreatic cystic precursors currently relies on imaging and cyst fluid evaluations, including cytology and protein and genomic analyses. However, there are persistent limitations that obstruct the accuracy and quality of information for clinicians, including the limited volume of the complex, often acellular, and proteinaceous milieu that comprises pancreatic cyst fluid. The constraints of currently available clinical assays lead clinicians to the subjective and inconsistent application of diagnostic tools, which can contribute to unnecessary surgery and missed pancreatic cancers. Herein, we describe the pathway toward pancreatic cyst classification and diagnosis, the volume requirements for several clinically available diagnostic tools, and some analytical and diagnostic limitations for each assay. We then discuss current and future work on novel markers and methods, and how to expand the utility of clinical pancreatic cyst fluid samples. Results of ongoing studies applying SERS as a detection mode suggest that 50 µL of pancreatic cyst fluid is more than sufficient to accurately rule out non-mucinous pancreatic cysts with no malignant potential from further evaluation. This process is expected to leave sufficient fluid to analyze a follow-up, rule-in panel of markers currently in development that can stratify grades of dysplasia in mucinous pancreatic cysts and improve clinical decision-making

Increased male reproductive success in Ts65Dn “Down syndrome” mice

The Ts65Dn mouse is trisomic for orthologs of about half the genes on Hsa21. A number of phenotypes in these trisomic mice parallel those in humans with trisomy 21 (Down syndrome), including cognitive deficits due to hippocampal malfunction that are sufficiently similar to human that “therapies” developed in Ts65Dn mice are making their way to human clinical trials. However, the impact of the model is limited by availability. Ts65Dn cannot be completely inbred and males are generally considered to be sterile. Females have few, small litters and they exhibit poor care of offspring, frequently abandoning entire litters. Here we report identification and selective breeding of rare fertile males from two working colonies of Ts65Dn mice. Trisomic offspring can be propagated by natural matings or by in vitro fertilization (IVF) to produce large cohorts of closely related siblings. The use of a robust euploid strain as recipients of fertilized embryos in IVF or as the female in natural matings greatly improves husbandry. Extra zygotes cultured to the blastocyst stage were used to create trisomic and euploid embryonic stem (ES) cells from littermates. We developed parameters for cryopreserving sperm from Ts65Dn males and used it to produce trisomic offspring by IVF. Use of cryopreserved sperm provides additional flexibility in the choice of oocyte donors from different genetic backgrounds, facilitating rapid production of complex crosses. This approach greatly increases the power of this important trisomic model to interrogate modifying effects of trisomic or disomic genes that contribute to trisomic phenotypes

Nutritional care is a human right: Translating principles to clinical practice

We have previously advocated that nutritional care be raised to the level of a human right, in close relationship to two well-recognized fundamental rights: the right to food and the right to health. This article aims to analyze the implication of nutritional care as a human right for healthcare practitioners. We will focus on the impact of the Human Rights Basic Approach (HRBA) on healthcare professionals (HCPs), namely how they can translate HRBA into routine clinical practice. Ethics and human rights are guiding values for clinical nutrition practitioners. Together they ensure a patient-centered approach, in which the needs and rights of the patients are of the most significant importance. Human rights are based on the powerful idea of equal dignity for all people while expressing a set of core values, including fairness, respect, equality, dignity, and autonomy (FREDA). Through the analysis of FREDA principles, we have provided the elements to understand human rights and how an HRBA can support clinicians in the decision-making process. Clinical practice guidelines in clinical nutrition should incorporate disease-specific ethical issues and the HRBA. The HRBA should contribute to building conditions for HCPs to provide optimal and timely nutritional care. Nutritional care must be exercised by HCPs with due respect for several fundamental ethical values: attentiveness, responsibility competence, responsiveness, and solidarity

Nutritional care is a human right: Translating principles to clinical practice

We have previously advocated that nutritional care be raised to the level of a human right in a close relationship to two well recognized fundamental rights: the right to food and the right to health. This paper aims to analyze the implication of nutritional care as a human right for healthcare practitioners. We will focus on the impact of the Human Rights Basic Approach (HRBA) on health care professionals (HCPs), namely how they can translate HRBA into routine clinical practice. Ethics and human rights are guiding values for clinical nutrition practitioners. Together they ensure a patient-centered approach, where the needs and rights of the patients are of the most significant importance. Human rights are based on the powerful idea of equal dignity for all people while expressing a set of core values, including fairness, respect, equality, dignity, and autonomy (FREDA). Through the analysis of FREDA principles, we have provided the elements to understand human rights and how a HRBA can support clinicians in the decision-making process. Clinical practice guidelines in clinical nutrition should incorporate disease-specific ethical issues and the HRBA. The HRBA should contribute to build conditions for HCPs to provide optimal and timely nutritional care. Nutritional care must be exercised by HCPs with due respect for several fundamental ethical values: attentiveness, responsibility competence, responsiveness, and solidarity

Internally Electrodynamic Particle Model: Its Experimental Basis and Its Predictions

The internally electrodynamic (IED) particle model was derived based on overall experimental observations, with the IED process itself being built directly on three experimental facts, a) electric charges present with all material particles, b) an accelerated charge generates electromagnetic waves according to Maxwell's equations and Planck energy equation and c) source motion produces Doppler effect. A set of well-known basic particle equations and properties become predictable based on first principles solutions for the IED process; several key solutions achieved are outlined, including the de Broglie phase wave, de Broglie relations, Schr\"odinger equation, mass, Einstein mass-energy relation, Newton's law of gravity, single particle self interference, and electromagnetic radiation and absorption; these equations and properties have long been broadly experimentally validated or demonstrated. A specific solution also predicts the Doebner-Goldin equation which emerges to represent a form of long-sought quantum wave equation including gravity. A critical review of the key experiments is given which suggests that the IED process underlies the basic particle equations and properties not just sufficiently but also necessarily.Comment: Presentation at the 27th Int Colloq on Group Theo Meth in Phys, 200

On the verge of Umdeutung in Minnesota: Van Vleck and the correspondence principle (Part One)

In October 1924, the Physical Review, a relatively minor journal at the time, published a remarkable two-part paper by John H. Van Vleck, working in virtual isolation at the University of Minnesota. Van Vleck combined advanced techniques of classical mechanics with Bohr's correspondence principle and Einstein's quantum theory of radiation to find quantum analogues of classical expressions for the emission, absorption, and dispersion of radiation. For modern readers Van Vleck's paper is much easier to follow than the famous paper by Kramers and Heisenberg on dispersion theory, which covers similar terrain and is widely credited to have led directly to Heisenberg's "Umdeutung" paper. This makes Van Vleck's paper extremely valuable for the reconstruction of the genesis of matrix mechanics. It also makes it tempting to ask why Van Vleck did not take the next step and develop matrix mechanics himself.Comment: 82 page