Effect of native gastric mucus on in vivo hybridization therapies directed at Helicobacter pylori

Helicobacter pylori infects more than 50% of the worldwide population. It is mostly found deep in the gastric mucus lining of the stomach, being a major cause of peptic ulcers and gastric adenocarcinoma. To face the increasing resistance of H. pylori to antibiotics, antimicrobial nucleic acid mimics are a promising alternative. In particular, locked nucleic acids (LNA)/2'-OMethyl RNA (2'OMe) have shown to specifically target H. pylori, as evidenced by in situ hybridization. The success of in vivo hybridization depends on the ability of these nucleic acids to penetrate the major physical barriers-the highly viscoelastic gastric mucus and the bacterial cell envelope. We found that LNA/2'OMe is capable of diffusing rapidly through native, undiluted, gastric mucus isolated from porcine stomachs, without degradation. Moreover, although LNA/2'OMe hybridization was still successful without permeabilization and fixation of the bacteria, which is normally part of in vitro studies, the ability of LNA/2'OMe to efficiently hybridize with H. pylori was hampered by the presence of mucus. Future research should focus on developing nanocarriers that shield LNA/2'OMe from components in the gastric mucus, while remaining capable of diffusing through the mucus and delivering these nucleic acid mimics directly into the bacteria

Output power limitations and improvements in passively mode locked GaAs/AlGaAs quantum well lasers

We report a novel approach for increasing the output power in passively mode locked semiconductor lasers. Our approach uses epitaxial structures with an optical trap in the bottom cladding that enlarges the vertical mode size to scale the pulse saturation energy. With this approach we demonstrate a very high peak power of 9.8 W per facet, at a repetition rate of 6.8 GHz and with pulse duration of 0.71 ps. In particular, we compare two GaAs/AlGaAs epilayer designs, a double quantum well design operating at 830 nm and a single quantum well design operating at 795 nm, with vertical mode sizes of 0.5 and 0.75 μm, respectively. We show that a larger mode size not only shifts the mode locking regime of operation toward higher powers, but also produces other improvements with respect to two main failure mechanisms that limit the output power, catastrophic optical mirror damage and catastrophic optical saturable absorber damage. For the 830-nm material structure, we also investigate the effect of nonabsorbing mirrors on output power and mode locked operation of colliding pulse mode locked lasers

Neural Distributed Autoassociative Memories: A Survey

Introduction. Neural network models of autoassociative, distributed memory allow storage and retrieval of many items (vectors) where the number of stored items can exceed the vector dimension (the number of neurons in the network). This opens the possibility of a sublinear time search (in the number of stored items) for approximate nearest neighbors among vectors of high dimension. The purpose of this paper is to review models of autoassociative, distributed memory that can be naturally implemented by neural networks (mainly with local learning rules and iterative dynamics based on information locally available to neurons). Scope. The survey is focused mainly on the networks of Hopfield, Willshaw and Potts, that have connections between pairs of neurons and operate on sparse binary vectors. We discuss not only autoassociative memory, but also the generalization properties of these networks. We also consider neural networks with higher-order connections and networks with a bipartite graph structure for non-binary data with linear constraints. Conclusions. In conclusion we discuss the relations to similarity search, advantages and drawbacks of these techniques, and topics for further research. An interesting and still not completely resolved question is whether neural autoassociative memories can search for approximate nearest neighbors faster than other index structures for similarity search, in particular for the case of very high dimensional vectors.Comment: 31 page

Len Yi Part 2

avi videoINTRODUCTION: Sonan Jetsun (Bsod nams rgyal mtshan) filmed this material 12-22 January 2008 in Len yi (Lianyi) Village, Sgong po (Gongbo) Township, Sde rong (Derong) County, Dkar mdzes (Ganzi) Tibetan Autonomous Prefecture, Si khron (Sichuan) Province, PR China. The film features the Tibetan New Year, Bkra shis Temple, and ordinary people's lives in Len yi Village. Sonan Jetsun also edited the material and plans to give it to Len yi villagers on DVD/ VCD. LOCATION: Lianyi Village is 200 kilometers southwest of Sde rong County Town, 550 kilometers from Dar rtse mdo (Kangding) City (the capital of Dkar mdzes Tibetan Autonomous Prefecture). The village has eighty households (560 Tibetans). Each family has an average of seven members, representing three generations. Most villagers were born after 1953. Villagers are agro-pastoralists, followers of the Dge lugs pa (Yellow Sect) of Tibetan Buddhism, and speak a distinctive Tibetan dialect. HORSE RACE: On the fifth day of the Tibetan New Year, a horse race is held on the mountainside. Nearly all the villagers attend the horse race, except for very old people. People ride horses and mules from the bottom of the valley to the valley's highest point. When the race is finished, prizes are given to first, second, and third place winners. After the race, many kha btags (white silk scarf) are tied around the winning animal's neck. LAB RTSE: The featured lab rtse is on 'bru lung Mountain, a twenty minute horse ride from Len yi Village. It was built as a place to make offerings to the mountain deity, A myes 'bru lung. Only men visit this mountain deity. It is believed that the deity will be angry if women climb 'bru lung Mountain. On the second day of the Tibetan New Year, each family sends one man on horseback to visit the mountain deity. They put dar lcog (prayer flags), bamboo, branches of trees, and other things into the lab rtse. Next, they chant prayers and burn bsang in front of the lab rtse, and circumambulate the lab rtse three times. Then, they have a picnic for a few hours beneath the lab rtse. TRADITIONAL CIRCLE DANCE: The circle dance is the most common performance in the village and is performed at such times as wedding parties, a celebration marking the building of a new house, and gatherings during the New Year. People sing as they dance. A stringed instrument (resembling the two-stringed Chinese upright fiddle) known as the bewong in the local dialect is played by men

Deconstructing the eradication of new world screwworm in North America: retrospective analysis and climate warming effects.

Before its eradication from North America, the subtropical-tropical new world screwworm fly Cochliomyia hominivorax (Coquerel) invaded southwestern temperate areas of the U.S.A., where it caused myiasis in wildlife and livestock. Outbreaks of the fly occurred during years when adult migrants were carried northward on North American monsoon winds from the northern areas of Mexico and south Texas. We deconstruct, retrospectively, the biology and the effect of weather on the eradication of the fly in North America. Screwworm was found to be an ideal candidate for eradication using the sterile insect technique (SIT) because females mate only once, whereas males are polygynous, and, although it has a high reproductive potential, field population growth rates are low in tropical areas. In northern areas, eradication was enhanced by cool-cold weather, whereas eradication in tropical Mexico and Central America is explained by the SIT. Despite low average efficacy of SIT releases (approximately 1.7%), the added pressure of massive SIT releases reduced intrinsically low fly populations, leading to mate-limited extinction. Non-autochthonous cases of myiasis occur in North America and, if the fly reestablishes, climate warming by 2045-2055 will expand the area of favourability and increase the frequency and severity of outbreaks

Multiple Outlier Detection in Samples with Exponential & Pareto Tails: Redeeming the Inward Approach & Detecting Dragon Kings

We consider the detection of multiple outliers in Exponential and Pareto samples -- as well as general samples that have approximately Exponential or Pareto tails, thanks to Extreme Value Theory. It is shown that a simple "robust" modification of common test statistics makes inward sequential testing -- formerly relegated within the literature since the introduction of outward testing -- as powerful as, and potentially less error prone than, outward tests. Moreover, inward testing does not require the complicated type 1 error control of outward tests. A variety of test statistics, employed in both block and sequential tests, are compared for their power and errors, in cases including no outliers, dispersed outliers (the classical slippage alternative), and clustered outliers (a case seldom considered). We advocate a density mixture approach for detecting clustered outliers. Tests are found to be highly sensitive to the correct specification of the main distribution (Exponential/Pareto), exposing high potential for errors in inference. Further, in five case studies -- financial crashes, nuclear power generation accidents, stock market returns, epidemic fatalities, and cities within countries -- significant outliers are detected and related to the concept of "Dragon King" events, defined as meaningful outliers of unique origin.Comment: 32 pages with 8 figure