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What we found in the sofa and how it saved the world
Finding a rare zucchini-colored crayon leads twelve-year-old River Monroe and his friends on an adventure with their eccentric neighbor to save Earth from invading interstellar storm troopers.
Book
Empirical investigations into Kruskal-Wallis power studies utilizing Bernstein fits, simulations and medical study datasets
Bernstein fits implemented into R allow another route for Kruskal-Wallis power-study tool development. Monte-Carlo Kruskal-Wallis power studies were compared with measured power, a Monte-Carlo ANOVA equivalent and with an analytical method, with or without normalization, using four simulated runs, each with 60–100 populations (each population with N = 30,000 from a set of Pearson-type ranges): random selection gave 6300 samples analyzed for predictive power. Three medical-study datasets (Dialysis/systolic blood pressure; Diabetes/sleep-hours; Marital-status/high-density-lipoprotein cholesterol) were also analyzed. In three from four simulated runs (run_one, run_one_relaxed, and run_three) with Pearson types pooled, Monte-Carlo Kruskal-Wallis gave predicted sample sizes significantly slightly lower than measured but more accurate than with ANOVA methods; the latter gave high sample-size predictions. Populations (run_one_relaxed) with ANOVA assumptions invalid gave Kruskal-Wallis predictions similar to those measured. In two from three medical studies, Kruskal-Wallis predictions (Dialysis: similar predictions; Marital: higher than measured) were more accurate than ANOVA (both higher than measured) but in one (Diabetes) the reverse was found (Kruskal-Wallis: lower; Monte-Carlo ANOVA: similar to measured). These preliminary studies appear to show that Monte-Carlo Kruskal-Wallis power studies, based on Bernstein fits, might perform better than ANOVA equivalents in many settings (and provide reasonable results when ANOVA cannot be used); and both Monte-Carlo methods appeared to be considerably more accurate than the analytical version analyzed.
Journal Article
Mass effect
\"Follow Miranda Lawson and Jacob Taylor as they chase Commander Shepard to the lawless and dangerous Terminus Systems, where no training can prepare them for what they'll find. Then join the beautiful and cunning Agent Rasa as she hunts the lethal biotic powerhouse Jack and crosses paths with the deadly master assassin Thane Krios\"-- Provided by publisher.
Book
Association of Genetically Predicted Activity of AMP Deaminase 1 with Clinical and Biochemical Parameters in Diabetic Individuals with Coronary Artery Disease
Some reports indicated the association of rs17602729 and rs34526199 functional polymorphisms of the AMPD1 gene encoding adenosine monophosphate deaminase 1 (AMPD1) with the risk of coronary artery disease (CAD) and/or its intermediate phenotype. Therefore, the aim of our study was to analyze the association of both AMPD1 polymorphisms with the predisposition to disease and both clinical and biochemical phenotypes but solely in diabetic individuals with CAD. The study group consisted of 196 adult diabetic individuals with CAD, and the control group comprised 200 healthy newborns. Both AMPD1 polymorphisms were identified by a SNaPshot minisequencing reaction. Clinical and laboratory data were taken from patients’ records. There were no significant differences between both groups in the frequency distributions of AMPD1:rs17602729 and rs34526199 alleles or genotypes. BMI and the frequency of obesity in TT rs17602729 homozygotes (no AMPD1 activity) were significantly lower and the serum concentration of HDL cholesterol was significantly higher compared to other patients. The concentrations of total cholesterol and LDL cholesterol in homozygotes for wild-type AMPD1:rs17602729 (c.34C) and rs34526199 (c.860A) alleles (full AMPD1 activity) were significantly lower compared to its values in other patients. Our results suggest that genetically predicted activity of AMPD1 is associated with variation in body mass and lipid metabolism in diabetic Polish people with CAD.
Journal Article
Sideband cooling beyond the quantum backaction limit with squeezed light
Squeezed light is used to sideband cool the motion of a macroscopic mechanical object below the limit imposed by quantum fluctuations.
Squeezed light cools a mechanical system below its quantum limit
Using techniques developed in quantum optomechanics, which studies the interaction between light and mechanical objects, researchers have been able to cool massive mechanical objects to temperature regimes close to the limit imposed by quantum fluctuations. These quantum fluctuations are a consequence of the uncertainty principle, because the position and momentum of a quantum-mechanical particle are never fixed, but rather fluctuate constantly. John Teufel and colleagues show how they can cool these massive mechanical objects even further by using 'squeezed' light—light in which the quantum noise, also arising from the uncertainty principle, has been reduced by redistributing the underlying uncertainty. This technique may allow for cooling larger and larger mechanical objects to lower and lower temperatures for metrology applications and fundamental tests of quantum mechanics.
Quantum fluctuations of the electromagnetic vacuum produce measurable physical effects such as Casimir forces and the Lamb shift
1
. They also impose an observable limit—known as the quantum backaction limit—on the lowest temperatures that can be reached using conventional laser cooling techniques
2
,
3
. As laser cooling experiments continue to bring massive mechanical systems to unprecedentedly low temperatures
4
,
5
, this seemingly fundamental limit is increasingly important in the laboratory
6
. Fortunately, vacuum fluctuations are not immutable and can be ‘squeezed’, reducing amplitude fluctuations at the expense of phase fluctuations. Here we propose and experimentally demonstrate that squeezed light can be used to cool the motion of a macroscopic mechanical object below the quantum backaction limit. We first cool a microwave cavity optomechanical system using a coherent state of light to within 15 per cent of this limit. We then cool the system to more than two decibels below the quantum backaction limit using a squeezed microwave field generated by a Josephson parametric amplifier. From heterodyne spectroscopy of the mechanical sidebands, we measure a minimum thermal occupancy of 0.19 ± 0.01 phonons. With our technique, even low-frequency mechanical oscillators can in principle be cooled arbitrarily close to the motional ground state, enabling the exploration of quantum physics in larger, more massive systems.
Journal Article
rs67047829 genotypes of ERV3-1/ZNF117 are associated with lower body mass index in the Polish population
There is now substantial evidence that zinc-finger proteins are implicated in adiposity. Aims were to datamine for high-frequency (near-neutral selection) pretermination-codon (PTC) single-nucleotide polymorphisms (SNPs; n = 141) from a database with > 550,000 variants and analyze possible association with body mass index in a large Polish sample (n = 5757). BMI was regressed (males/females together or separately) against genetic models. Regression for rs67047829 uncovered an interaction-independent association with BMI with both sexes together: mean ± standard deviation, kg/m
2
: [G];[G], 25.4 ± 4.59 (n = 3650); [G](;)[A], 25.0 ± 4.28 (n = 731); [A];[A], 23.4 ± 3.60 (n = 44); additive model adjusted for age and sex: p = 4.08 × 10
–5
; beta: − 0.0458, 95% confidence interval (CI) − 0.0732 : − 0.0183; surviving Bonferroni correction; for males: [G];[G], 24.8 ± 4.94 (n = 1878); [G](;)[A], 24.2 ± 4.31 (n = 386); [A];[A], 22.4 ± 3.69 (n = 23); p = 4.20 × 10
–4
; beta: − 0.0573, CI − 0.0947 : − 0.0199. For average-height males the difference between [G];[G] and [A];[A] genotypes would correspond to ~ 6 kg, suggesting considerable protection against increased BMI. rs67047829 gives a pretermination codon in
ERV3-1
which shares an exonic region and possibly promoter with
ZNF117
, previously associated with adiposity and type-2 diabetes. As this result occurs in a near-neutral Mendelian setting, a drug targetting
ERV3-1/ZNF117
might potentially provide considerable benefits with minimal side-effects. This result needs to be replicated, followed by analyses of splice-variant mRNAs and protein expression.
Journal Article
No Association of Polymorphisms in the Genes Encoding Interleukin-6 and Interleukin-6 Receptor Subunit Alpha with the Risk of Keloids in Polish Patients
A keloid is a benign fibroproliferative hypertrophy of scar tissue that extends outside the original wound and invades adjacent healthy skin. Keloid formation is thought to be a complex process including overactivity of the interleukin-6 signaling pathway and genetic susceptibility. The aim of the study was to investigate possible associations between rs1800797, rs1800796, and rs1800795 polymorphisms in the promoter of the IL6 gene encoding interleukin-6 and the rs2228145 polymorphism in the IL6R gene encoding the interleukin-6 receptor subunit alpha with the predisposition to keloids in Polish patients. The genetic polymorphisms were identified either using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) or sequencing of samples of genomic DNA extracted from blood leukocytes of 86 adult patients with keloids and 100 newborns comprising a control group. No significant differences in the distributions of IL6 or IL6R alleles or genotypes were found between keloid patients and newborn controls. There were also no significant differences between both groups in the distribution of IL6 haplotypes. The IL6 rs1800797, rs1800796 and rs1800795 and IL6R rs2228145 polymorphisms were not found to predispose individuals in the study group to keloids. IL6 promoter haplotypes were not found to be associated with a higher risk of keloids in the studied group.
Journal Article
Observation of strong radiation pressure forces from squeezed light on a mechanical oscillator
Non-classical states of light, such as squeezed states, are used in quantum metrology to improve the sensitivity of mechanical motion sensing, but conversely mechanical oscillations can enhance the measurement of squeezed light.
In quantum-enhanced sensing, non-classical states are used to improve the sensitivity of a measurement
1
. Squeezed light, in particular, has proved a useful resource in enhanced mechanical displacement sensing
2
,
3
,
4
,
5
,
6
,
7
,
8
, although the fundamental limit to this enhancement due to the Heisenberg uncertainty principle
9
,
10
,
11
has not been encountered experimentally. Here we use a microwave cavity optomechanical system to observe the squeezing-dependent radiation pressure noise that necessarily accompanies any quantum enhancement of the measurement precision and ultimately limits the measurement noise performance. By increasing the measurement strength so that radiation pressure forces dominate the thermal motion of the mechanical oscillator, we exploit the optomechanical interaction to implement an efficient quantum nondemolition measurement of the squeezed light
12
. Thus, our results show how the mechanical oscillator improves the measurement of non-classical light, just as non-classical light enhances the measurement of the motion.
Journal Article
Association studies between chromosomal regions 1q21.3, 5q21.3, 14q21.2 and 17q21.31 and numbers of children in Poland
Number of children is an important human trait and studies have indicated associations with single-nucleotide polymorphisms (SNPs). Aim: to give further evidence for four associations using a large sample of Polish subjects. Data from the POPULOUS genetic database was provided from anonymous, healthy, unrelated, Polish volunteers of both sexes (N = 5760). SNPs (n = 173) studied: (a) 69 from the chromosome 17 H1/H2 inversion; (b) six from 1q21.3, 5q21.3 and 14q21.2; and (c) 98 random negative controls. Zero-inflated negative-binomial regression (z.i.) was performed (0–3 numbers of children per individual (NCI) set as non-events; adjustors: year of birth, sex). Significance level
p
= 0.05 with Bonferroni correction. Statistically-significant differences (with data from both sexes combined) were obtained from highly-linked inversion SNPs: representative rs12373123 gave means: homozygotes TT: 2.31 NCI (n = 1418); heterozygotes CT: 2.35 NCI (n = 554); homozygotes CC: 2.44 NCI (n = 43) (genotype
p
= 0.01; TTvs.CC
p
= 0.004; CTvs.CC
p
= 0.009). (Male data alone gave similar results.) Recessive modeling indicated that H2-homozygotes had 0.118 more children than H1-homozygotes + heterozygotes (z.i.-count estimates ± standard errors: CT, − 0.508 ± 0.194; TT, − 0.557 ± 0.191). The non-over-dispersed count model detected no interactions: of importance there was no significant interaction with age. No positive results were obtained from negative-control SNPs or (b). Conclusions: association between the H1/H2 inversion and numbers of children (previously reported in Iceland) has been confirmed, albeit using a different statistical model. One limitation is the small amount of data, despite initially ~ 6000 subjects. Causal studies require further investigation.
Journal Article
Orally consumed cannabinoids provide long-lasting relief of allodynia in a mouse model of chronic neuropathic pain
Chronic pain affects a significant percentage of the United States population, and available pain medications like opioids have drawbacks that make long-term use untenable. Cannabinoids show promise in the management of pain, but long-term treatment of pain with cannabinoids has been challenging to implement in preclinical models. We developed a voluntary, gelatin oral self-administration paradigm that allowed male and female mice to consume ∆9-tetrahydrocannabinol, cannabidiol, or morphine ad libitum. Mice stably consumed these gelatins over 3 weeks, with detectable serum levels. Using a real-time gelatin measurement system, we observed that mice consumed gelatin throughout the light and dark cycles, with animals consuming less THC-gelatin than the other gelatin groups. Consumption of all three gelatins reduced measures of allodynia in a chronic, neuropathic sciatic nerve injury model, but tolerance to morphine developed after 1 week while THC or CBD reduced allodynia over three weeks. Hyperalgesia gradually developed after sciatic nerve injury, and by the last day of testing, THC significantly reduced hyperalgesia, with a trend effect of CBD, and no effect of morphine. Mouse vocalizations were recorded throughout the experiment, and mice showed a large increase in ultrasonic, broadband clicks after sciatic nerve injury, which was reversed by THC, CBD, and morphine. This study demonstrates that mice voluntarily consume both cannabinoids and opioids via gelatin, and that cannabinoids provide long-term relief of chronic pain states. In addition, ultrasonic clicks may objectively represent mouse pain status and could be integrated into future pain models.
Journal Article