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Enterohemorrhagic Escherichia coli (EHEC) is a major cause of severe bloody diarrhea, with potentially lethal complications, such as hemolytic uremic syndrome. In humans, EHEC colonizes the colon, which is also home to a diverse community of trillions of microbes known as the gut microbiota. Although these microbes and the metabolites that they produce represent an important component of EHEC's ecological niche, little is known about how EHEC senses and responds to the presence of gut microbiota metabolites. In this study, we used a combined RNA-Seq and Tn-Seq approach to characterize EHEC's response to metabolites from an in vitro culture of 33 human gut microbiota isolates (MET-1), previously demonstrated to effectively resolve recurrent Clostridioides difficile infection in human patients. Collectively, the results revealed that EHEC adjusts to growth in the presence of microbiota metabolites in two major ways: by altering its metabolism and by activating stress responses. Metabolic adaptations to the presence of microbiota metabolites included increased expression of systems for maintaining redox balance and decreased expression of biotin biosynthesis genes, reflecting the high levels of biotin released by the microbiota into the culture medium. In addition, numerous genes related to envelope and oxidative stress responses (including cpxP, spy, soxS, yhcN, and bhsA) were upregulated during EHEC growth in a medium containing microbiota metabolites. Together, these results provide insight into the molecular mechanisms by which pathogens adapt to the presence of competing microbes in the host environment, which ultimately may enable the development of therapies to enhance colonization resistance and prevent infection.

Virus-like particles (VLPs) have been extensively explored as vaccine candidates since the mid-1980s. Numerous VLPs have been designed as vaccines for prevention of virus-induced infectious diseases and for the therapeutical treatment of chronic diseases and drug addiction. Recently, a vaccine against nicotine addiction, which is based on VLPs of the RNA phage Qb to which nicotine haptens are covalently coupled via succinimate linkers (NicQb), has attracted a great deal of interest. Phase II clinical trials with this vaccine have shown that it is efficacious for smoking cessation in humans when antinicotine antibody levels are sufficiently high. For commercialization, the development of stable formulations enabling storage for prolonged periods is required. Hereby, lyophilization, a well-established method leading to stable and dry formulations, is often applied. In this study, we investigated the influence of different pH values and various excipients such as surfactants, polyols, sugars, and salts on the stability of NicQb in liquid formulations, during freeze thawing, freeze drying, and finally upon storage of the dried product. Lyophilized NicQb formulations were developed which were stable over 6 months at ambient temperature with fully retained biological activity. Hereby, it was found that a combination of the surfactant polysorbate 20 and the disaccharide trehalose was capable to prevent NicQb aggregation and to preserve its integrity (nicotine binding and integrity of VLP shell). Furthermore, asymmetrical flow field-flow fractionation (AF4), a new, promising analytical tool, was established for the investigation of VLP stability.

In the single vehicle routing allocation problem (SVRAP) we have a single vehicle, together with a set of customers, and the problem is one of deciding a route for the vehicle (starting and ending at given locations) such that it visits some of the customers. Customers not visited by the vehicle can either be allocated to a customer on the vehicle route, or they can be isolated. The objective is to minimize a weighted sum of routing, allocation and isolation costs. One special case of the general SVRAP is the median cycle problem, also known as the ring star problem, where no isolated vertices are allowed. Other special cases include the covering tour problem, the covering salesman problem and the shortest covering path problem. In this paper, we present a tabu search algorithm for the SVRAP. Our tabu search algorithm includes aspiration, path relinking and frequency-based diversification. Computational results are presented for test problems used previously in the literature and our algorithm is compared with the results obtained by other researchers. We also report results for much larger problems than have been considered by others.

In five subjects arterial and central venous nitrogen partial pressures (PN2) were measured after decompression from a chamber dive following a decompression schedule for scuba diving. The simulated dives consisted of exposure at rest to air at 6 bar for 30 min. corresponding to a depth of 50 m. Afterwards the subjects were decompressed with decompression stops at 2.5, 2.2, 1.9, 1.6 and 1.3 bar with a total decompression time of 73 min. Immediately after decompression and every 40 min. until the 240th min. arterial and central venous blood samples were analyzed for PN2 using a manometric Van Slyke apparatus. Venous PN2 remained elevated until 160 min. after decompression indicating still incomplete nitrogen wash-out at least two hours after decompression had been accomplished. Bubble formation is discussed as a cause for prolonged nitrogen elimination. Our data confirm that nitrogen elimination is prolonged after decompression from simulated dives at rest.

The paper deals with so-called generalized sampling sums stemming from the well-known Shannon sampling series; here the sine-function is replaced by suitable time limited even kernel functions. It is shown that the best possible rate of approximation for such processes to functions of class C(IR) is c)(w&-2m-2), where 2m is the number of sign changes of the kernel and the sampling rate is w-1. Furthermore, a general method for the construction of linear combinations-of positive kernels leading to such approximation rates is presented.

Archives and libraries have emphasized their differences rather than commonalities, and have so specialized within their own developmental traditions that cooperation has been an illusive ideal. Archivists are now moving toward a national or more accurately nationwide system of information exchange after a decade of false starts and consensus building. The National Historical Publications and Records Commission has been a major stimulus for cooperative development. By 1985 the key elements for a national system were identified and now questions of actual development and leadership are being discussed. Funding is always critical for such developments, but planning must face continued austerity and yet proceed.

The purpose of this paper is to present a systematic treatment of central factorial numbers (cfn), including their main properties, as well as to employ them in a variety of applications. The cfn are related more closely to the Stirling numbers than to the other well-known numbers of Bernoulli, Euler, etc., and they are at least as important as Stirling's numbers, said to be “as important as Bernoulli's, or even more so”.

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