236 research outputs found

    On the complexity of the multiple stack TSP, kSTSP

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    The multiple Stack Travelling Salesman Problem, STSP, deals with the collect and the deliverance of n commodities in two distinct cities. The two cities are represented by means of two edge-valued graphs (G1,d2) and (G2,d2). During the pick-up tour, the commodities are stored into a container whose rows are subject to LIFO constraints. As a generalisation of standard TSP, the problem obviously is NP-hard; nevertheless, one could wonder about what combinatorial structure of STSP does the most impact its complexity: the arrangement of the commodities into the container, or the tours themselves? The answer is not clear. First, given a pair (T1,T2) of pick-up and delivery tours, it is polynomial to decide whether these tours are or not compatible. Second, for a given arrangement of the commodities into the k rows of the container, the optimum pick-up and delivery tours w.r.t. this arrangement can be computed within a time that is polynomial in n, but exponential in k. Finally, we provide instances on which a tour that is optimum for one of three distances d1, d2 or d1+d2 lead to solutions of STSP that are arbitrarily far to the optimum STSP

    Nuclear DNA content in the subgenus Coffea (Rubiaceae) : inter and intra-specific variation in African species

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    La cytométrie en flux a été utilisée pour estimer la quantité d'ADN nucléaire chez 13 espèces de #Coffea (Rubiacea) originaires d'Afrique. Douze espèces diploïdes (#2n=22) et l'espèce tétraploïde #C. arabica (#2n=44) ont été analysées. Pour 77 génotypes, des populations de noyaux isolés ont été colorées par l'iodure de propidium (IP ; non spécifique des bases). Pour trente neuf génotypes, le 4',6-diamidino-2-phenylindole (DAPI; AT spécifique) a été également utilisé. Les quantités 2C d'ADN nucléaire, estimées avec l'IP, oscillent entre 0,95 et 1,78 pg. Trois groupes correspondant à des quantités croissantes d'ADN ont été mis en évidence. Les trois espèces #C. sessiliflora, C. racemosa et #C. pseudozanguebariae se classent dans le groupe des plus petites valeurs (groupe 1 : 0,90 à 1,30 pg). Les trois espèces #C. eugenioides, C. stenophylla et #C. sp. F. se rangent uniquement dans le groupe des valeurs intermédiaires (groupe 2 : 1,31 à 1,60 pg). Les autres espèces se répartissent entre le groupe 2 et le groupe des plus hautes valeurs (groupe 3 : 1,61 à 1,80 pg). Les valeurs déterminées pour les espèces de #Coffea$, sont comparées aux niveaux intra- et inter-spécifique à celles d'autres angiospermes. Les différences observées sont discutées en fonction de l'origine éco-géographique des espèces, leurs caractéristiques phénologiques et la fertilité de leurs hybrides F1 interspécifiques. (Résumé d'auteur

    Maternal age effect and severe germ-line bottleneck in the inheritance of human mitochondrial DNA

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    The manifestation of mitochondrial DNA (mtDNA) diseases depends on the frequency of heteroplasmy (the presence of several alleles in an individual), yet its transmission across generations cannot be readily predicted owing to a lack of data on the size of the mtDNA bottleneck during oogenesis. For deleterious heteroplasmies, a severe bottleneck may abruptly transform a benign (low) frequency in a mother into a disease-causing (high) frequency in her child. Here we present a high-resolution study of heteroplasmy transmission conducted on blood and buccal mtDNA of 39 healthy mother–child pairs of European ancestry (a total of 156 samples, each sequenced at ∼20,000× per site). On average, each individual carried one heteroplasmy, and one in eight individuals carried a disease-associated heteroplasmy, with minor allele frequency ≥1%. We observed frequent drastic heteroplasmy frequency shifts between generations and estimated the effective size of the germ-line mtDNA bottleneck at only ∼30–35 (interquartile range from 9 to 141). Accounting for heteroplasmies, we estimated the mtDNA germ-line mutation rate at 1.3 × 10−8 (interquartile range from 4.2 × 10−9 to 4.1 × 10−8) mutations per site per year, an order of magnitude higher than for nuclear DNA. Notably, we found a positive association between the number of heteroplasmies in a child and maternal age at fertilization, likely attributable to oocyte aging. This study also took advantage of droplet digital PCR (ddPCR) to validate heteroplasmies and confirm a de novo mutation. Our results can be used to predict the transmission of disease-causing mtDNA variants and illuminate evolutionary dynamics of the mitochondrial genome

    The complexity of the Pk partition problem and related problems in bipartite graphs

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    International audienceIn this paper, we continue the investigation made in [MT05] about the approximability of Pk partition problems, but focusing here on their complexity. Precisely, we aim at designing the frontier between polynomial and NP-complete versions of the Pk partition problem in bipartite graphs, according to both the constant k and the maximum degree of the input graph. We actually extend the obtained results to more general classes of problems, namely, the minimum k-path partition problem and the maximum Pk packing problem. Moreover, we propose some simple approximation algorithms for those problems

    What are Employers Looking for in New Veterinary Graduates? A Content Analysis of UK Veterinary Job Advertisements

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    As veterinary educators, we have a responsibility to ensure that our graduates are prepared for working life. Veterinary practices, like any other businesses, rely on good employees, and the implications of a poor match between newly employed veterinarian and employing practice could be extremely costly in terms of personal well-being and enjoyment of work as well as the time, financial, and goodwill costs of high staff turnover for the practice. Contemporary veterinary curricula encompass a range of teaching to complement the clinical content; including communication, teamwork, problem solving, and business skills, to support good practice and increase the employability of new graduates. Previous studies have examined the qualities required of early career veterinarians as viewed by educators, recent graduates, pet owners, and practitioners; however, nobody has previously constructed a picture of the employment market for new veterinary graduates by exploring the nature of its recruitment advertising. Three months of UK veterinary job advertisements were examined. Content analysis yielded 10 distinct characteristics desired by employers of early career veterinarians. The most common by far was “enthusiasm,” followed by an interest in a particular area of practice, being an “all-rounder” (i.e., having a broad range of skills), demonstrating good communication skills, teamwork, client care, and independence, as well as being caring, ambitious, and having high clinical standards. While several of these qualities are expected and are specifically taught in veterinary school, the dominance of “enthusiasm” as a specifically desired trait raises interesting questions about the characteristics of veterinary students who we are supporting, encouraging, or maybe even suppressing, during veterinary training

    The Diversity of Religious Diversity. Using Census and NCS Methodology in Order to Map and Assess the Religious Diversity of a Whole Country

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    Religious diversity is often captured in “mapping studies” that use mostly qualitative methods in order to map and assess the religious communities in a given area. While these studies are useful, they often present weaknesses in that they treat only limited geographic regions, provide limited possibilities for comparing across religious groups and cannot test theories. In this article, we show how a census and a quantitative national congregations study (NCS) methodology can be combined in order to map and assess the religious diversity of a whole country (Switzerland), overcoming the problems mentioned above. We outline the methodological steps and selected results concerning organizational, geographic, structural, and cultural diversity

    An Introduction to Temporal Graphs: An Algorithmic Perspective

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    A \emph{temporal graph} is, informally speaking, a graph that changes with time. When time is discrete and only the relationships between the participating entities may change and not the entities themselves, a temporal graph may be viewed as a sequence G1,G2,GlG_1,G_2\ldots,G_l of static graphs over the same (static) set of nodes VV. Though static graphs have been extensively studied, for their temporal generalization we are still far from having a concrete set of structural and algorithmic principles. Recent research shows that many graph properties and problems become radically different and usually substantially more difficult when an extra time dimension in added to them. Moreover, there is already a rich and rapidly growing set of modern systems and applications that can be naturally modeled and studied via temporal graphs. This, further motivates the need for the development of a temporal extension of graph theory. We survey here recent results on temporal graphs and temporal graph problems that have appeared in the Computer Science community

    Unprocessed Viral DNA Could Be the Primary Target of the HIV-1 Integrase Inhibitor Raltegravir

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    Integration of HIV DNA into host chromosome requires a 3′-processing (3′-P) and a strand transfer (ST) reactions catalyzed by virus integrase (IN). Raltegravir (RAL), commonly used in AIDS therapy, belongs to the family of IN ST inhibitors (INSTIs) acting on IN-viral DNA complexes (intasomes). However, studies show that RAL fails to bind IN alone, but nothing has been reported on the behaviour of RAL toward free viral DNA. Here, we assessed whether free viral DNA could be a primary target for RAL, assuming that the DNA molecule is a receptor for a huge number of pharmacological agents. Optical spectroscopy, molecular dynamics and free energy calculations, showed that RAL is a tight binder of both processed and unprocessed LTR (long terminal repeat) ends. Complex formation involved mainly van der Waals forces and was enthalpy driven. Dissociation constants (Kds) revealed that RAL affinity for unbound LTRs was stronger than for bound LTRs. Moreover, Kd value for binding of RAL to LTRs and IC50 value (half concentration for inhibition) were in same range, suggesting that RAL binding to DNA and ST inhibition are correlated events. Accommodation of RAL into terminal base-pairs of unprocessed LTR is facilitated by an extensive end fraying that lowers the RAL binding energy barrier. The RAL binding entails a weak damping of fraying and correlatively of 3′-P inhibition. Noteworthy, present calculated RAL structures bound to free viral DNA resemble those found in RAL-intasome crystals, especially concerning the contacts between the fluorobenzyl group and the conserved 5′C4pA33′ step. We propose that RAL inhibits IN, in binding first unprocessed DNA. Similarly to anticancer drug poisons acting on topoisomerases, its interaction with DNA does not alter the cut, but blocks the subsequent joining reaction. We also speculate that INSTIs having viral DNA rather IN as main target could induce less resistance

    Impairment of the Plasmodium falciparum Erythrocytic Cycle Induced by Angiotensin Peptides

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    Plasmodium falciparum causes the most serious complications of malaria and is a public health problem worldwide with over 2 million deaths each year. The erythrocyte invasion mechanisms by Plasmodium sp. have been well described, however the physiological aspects involving host components in this process are still poorly understood. Here, we provide evidence for the role of renin-angiotensin system (RAS) components in reducing erythrocyte invasion by P. falciparum. Angiotensin II (Ang II) reduced erythrocyte invasion in an enriched schizont culture of P. falciparum in a dose-dependent manner. Using mass spectroscopy, we showed that Ang II was metabolized by erythrocytes to Ang IV and Ang-(1–7). Parasite infection decreased Ang-(1–7) and completely abolished Ang IV formation. Similar to Ang II, Ang-(1–7) decreased the level of infection in an A779 (specific antagonist of Ang-(1–7) receptor, MAS)-sensitive manner. 10−7 M PD123319, an AT2 receptor antagonist, partially reversed the effects of Ang-(1–7) and Ang II. However, 10−6 M losartan, an antagonist of the AT1 receptor, had no effect. Gs protein is a crucial player in the Plasmodium falciparum blood cycle and angiotensin peptides can modulate protein kinase A (PKA) activity; 10−8 M Ang II or 10−8 M Ang-(1–7) inhibited this activity in erythrocytes by 60% and this effect was reversed by 10−7 M A779. 10−6 M dibutyryl-cAMP increased the level of infection and 10−7 M PKA inhibitor decreased the level of infection by 30%. These results indicate that the effect of Ang-(1–7) on P. falciparum blood stage involves a MAS-mediated PKA inhibition. Our results indicate a crucial role for Ang II conversion into Ang-(1–7) in controlling the erythrocytic cycle of the malaria parasite, adding new functions to peptides initially described to be involved in the regulation of vascular tonus
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