Feedback Cooling of a Single Neutral Atom

We demonstrate feedback cooling of the motion of a single rubidium atom trapped in a high-finesse optical resonator to a temperature of about 160 \mu K. Time-dependent transmission and intensity-correlation measurements prove the reduction of the atomic position uncertainty. The feedback increases the 1/e storage time into the one second regime, 30 times longer than without feedback. Feedback cooling therefore rivals state-of-the-art laser cooling, but with the advantages that it requires less optical access and exhibits less optical pumping.Comment: 5 pages, 4 figure

7‑hydroxymitragynine is an active metabolite of mitragynine and a key mediator of its analgesic effects

Mitragynina speciosa, more commonly known as kratom, is a plant native to Southeast Asia, the leaves of which have been used traditionally as a stimulant, analgesic, and treatment for opioid addiction. Recently, growing use of the plant in the United States and concerns that kratom represents an uncontrolled drug with potential abuse liability, have highlighted the need for more careful study of its pharmacological activity. The major active alkaloid found in kratom, mitragynine, has been reported to have opioid agonist and analgesic activity in vitro and in animal models, consistent with the purported effects of kratom leaf in humans. However, preliminary research has provided some evidence that mitragynine and related compounds may act as atypical opioid agonists, inducing therapeutic effects such as analgesia, while limiting the negative side effects typical of classical opioids. Here we report evidence that an active metabolite plays an important role in mediating the analgesic effects of mitragynine. We find that mitragynine is converted in vitro in both mouse and human liver preparations to the much more potent mu-opioid receptor agonist 7-hydroxymitragynine, and that this conversion is mediated by cytochrome P450 3A isoforms. Further, we show that 7-hydroxymitragynine is formed from mitragynine in mice and that brain concentrations of this metabolite are sufficient to explain most or all of the opioid-receptor-mediated analgesic activity of mitragynine. At the same time, mitragynine is found in the brains of mice at very high concentrations relative to its opioid receptor binding affinity, suggesting that it does not directly activate opioid receptors. The results presented here provide a metabolism-dependent mechanism for the analgesic effects of mitragynine and clarify the importance of route of administration for determining the activity of this compound. Further, they raise important questions about the interpretation of existing data on mitragynine and highlight critical areas for further research in animals and humans.</p

Observation of squeezed light from one atom excited with two photons

Single quantum emitters like atoms are well-known as non-classical light sources which can produce photons one by one at given times, with reduced intensity noise. However, the light field emitted by a single atom can exhibit much richer dynamics. A prominent example is the predicted ability for a single atom to produce quadrature-squeezed light, with sub-shot-noise amplitude or phase fluctuations. It has long been foreseen, though, that such squeezing would be "at least an order of magnitude more difficult" to observe than the emission of single photons. Squeezed beams have been generated using macroscopic and mesoscopic media down to a few tens of atoms, but despite experimental efforts, single-atom squeezing has so far escaped observation. Here we generate squeezed light with a single atom in a high-finesse optical resonator. The strong coupling of the atom to the cavity field induces a genuine quantum mechanical nonlinearity, several orders of magnitude larger than for usual macroscopic media. This produces observable quadrature squeezing with an excitation beam containing on average only two photons per system lifetime. In sharp contrast to the emission of single photons, the squeezed light stems from the quantum coherence of photon pairs emitted from the system. The ability of a single atom to induce strong coherent interactions between propagating photons opens up new perspectives for photonic quantum logic with single emittersComment: Main paper (4 pages, 3 figures) + Supplementary information (5 pages, 2 figures). Revised versio

Вибір та обґрунтування параметрів технології підтримки стінок стовбура свердловини в осадових породах

Практичне значення роботи полягає в досліджені широкого кола властивостей різних хімічних сполук, покликаних збільшити ступінь стійкості осадових порід в стінках стовбура свердловини; застосування досліджених речовин приведе до істотного підвищення продуктивності бурових робіт, скорочення часу на роботи, пов’язані із ліквідацією ускладнень і аварій в свердловині, або повного виключення останніх, загального зростання ефективності і економічності процесу спорудження свердловин.Мета дипломної роботи: встановлення закономірностей фізико-хімічних процесів, що протікають в стовбурі свердловини, споруджуваної в товщі осадових гірських порід, при циркуляції промивальних рідин і формулюванні на їх основі адекватних технологічних заходів гідравлічної програми промивання свердловини, реалізація якої дозволить надати процесу спорудження свердловин достатньо високу міру продуктивності і економічності

Focus on the management of thunderclap headache: from nosography to treatment

Thunderclap headache (TCH) is an excruciating headache characterized by a very sudden onset. Recognition and accurate diagnosis of TCH are important in order to rule out the various, serious underlying brain disorders that, in a high percentage of cases, are the real cause of the headache. Primary TCH, which may recur intermittently and generally has a spontaneous, benign evolution, can thus be diagnosed only when all other potential underlying causes have been excluded through accurate diagnostic work up. In this review, we focus on the management of TCH, paying particular attention to the diagnostic work up and treatment of the condition

A Ceratopsian Dinosaur from the Lower Cretaceous of Western North America, and the Biogeography of Neoceratopsia

Competing interests: Andrew A. Farke has read the journal's policy and the authors of this manuscript have the following competing interests: Andrew A. Farke is a volunteer section editor and academic editor for PLOS ONE. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials.Acknowledgments It is a pleasure to offer our most heartfelt thanks to Scott K. Madsen, who found OMNH 34557 and prepared it with consummate skill. We are grateful to James Taylor, Jack Owen, the Keebler family, and the Montana Bureau of Land Management for access to outcrops of the Cloverly Formation. We thank Xu Xing (IVPP) and Hai-Lu You (formerly CAGS-IG) for facilitating access to specimens, Mark Loewen, Joseph Frederickson, Darren Naish, and Leonardo Maiorino for productive discussion and comments, and Roger Burkhalter for assistance in photography. Gary Wisser, from the scientific visualization center at Western University of Health Sciences, is gratefully acknowledged for the high resolution scan of the cranium. Reviews by Peter Makovicky, Hai-Lu You, and editor Peter Wilf improved the manuscript.Author Contributions Conceived and designed the experiments: AAF WDM RLC. Performed the experiments: AAF WDM RLC. Analyzed the data: AAF WDM RLC MJW. Contributed reagents/materials/analysis tools: AAF WDM RLC MJW. Wrote the paper: AAF WDM RLC MJW.The fossil record for neoceratopsian (horned) dinosaurs in the Lower Cretaceous of North America primarily comprises isolated teeth and postcrania of limited taxonomic resolution, hampering previous efforts to reconstruct the early evolution of this group in North America. An associated cranium and lower jaw from the Cloverly Formation (?middle–late Albian, between 104 and 109 million years old) of southern Montana is designated as the holotype for Aquilops americanus gen. et sp. nov. Aquilops americanus is distinguished by several autapomorphies, including a strongly hooked rostral bone with a midline boss and an elongate and sharply pointed antorbital fossa. The skull in the only known specimen is comparatively small, measuring 84 mm between the tips of the rostral and jugal. The taxon is interpreted as a basal neoceratopsian closely related to Early Cretaceous Asian taxa, such as Liaoceratops and Auroraceratops. Biogeographically, A. americanus probably originated via a dispersal from Asia into North America; the exact route of this dispersal is ambiguous, although a Beringian rather than European route seems more likely in light of the absence of ceratopsians in the Early Cretaceous of Europe. Other amniote clades show similar biogeographic patterns, supporting an intercontinental migratory event between Asia and North America during the late Early Cretaceous. The temporal and geographic distribution of Upper Cretaceous neoceratopsians (leptoceratopsids and ceratopsoids) suggests at least intermittent connections between North America and Asia through the early Late Cretaceous, likely followed by an interval of isolation and finally reconnection during the latest Cretaceous.Funding was received from the National Science Foundation (DEB 9401094, 9870173, http://www.nsf.gov); National Geographic Society (5918-97, http://www.nationalgeographic.com/); and American Chemical Society (PRF #38572-AC8, http://www.acs.org). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Yeshttp://www.plosone.org/static/editorial#pee

Rheumatoid arthritis: pathological mechanisms and modern pharmacologic therapies.

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease that primarily affects the lining of the synovial joints and is associated with progressive disability, premature death, and socioeconomic burdens. A better understanding of how the pathological mechanisms drive the deterioration of RA progress in individuals is urgently required in order to develop therapies that will effectively treat patients at each stage of the disease progress. Here we dissect the etiology and pathology at specific stages: (i) triggering, (ii) maturation, (iii) targeting, and (iv) fulminant stage, concomitant with hyperplastic synovium, cartilage damage, bone erosion, and systemic consequences. Modern pharmacologic therapies (including conventional, biological, and novel potential small molecule disease-modifying anti-rheumatic drugs) remain the mainstay of RA treatment and there has been significant progress toward achieving disease remission without joint deformity. Despite this, a significant proportion of RA patients do not effectively respond to the current therapies and thus new drugs are urgently required. This review discusses recent advances of our  understanding of RA pathogenesis, disease modifying drugs, and provides perspectives on next generation therapeutics for RA

Neurotransmitter Detection Using Corona Phase Molecular Recognition on Fluorescent Single-Walled Carbon Nanotube Sensors

ABSTRACT: Temporal and spatial changes in neurotransmitter concentrations are central to information processing in neural networks. Therefore, biosensors for neurotransmitters are essential tools for neuroscience. In this work, we applied a new technique, corona phase molecular recognition (CoPhMoRe), to identify adsorbed polymer phases on fluorescent single-walled carbon nanotubes (SWCNTs) that allow for the selective detection of specific neurotransmitters, including dopamine. We functionalized and suspended SWCNTs with a library of different polymers (n = 30) containing phospholipids, nucleic acids, and amphiphilic polymers to study how neurotransmitters modulate the resulting band gap, near-infrared (nIR) fluorescence of the SWCNT. We identified several corona phases that enable the selective detection of neurotransmitters. Catecholamines such as dopamine increased the fluorescence of specific single-stranded DNA- and RNA-wrapped SWCNTs by 58−80 % upon addition of 100 μM dopamine depending on the SWCNT chirality (n,m). In solution, the limit of detection was 11 nM [Kd = 433 nM for (GT)15 DNA-wrapped SWCNTs]. Mechanistic studies revealed that this turn-on response is due to an increase in fluorescence quantum yield and not covalent modification of the SWCNT or scavenging o