Modular logic gates: cascading independent logic gates via metal ion signals

Cataloged from PDF version of article.Abstract Systematic cascading of molecular logic gates is an important issue to be addressed for advancing research in this field. We have demonstrated that photochemically triggered metal ion signals can be utilized towards that goal. Thus, independent logic gates were shown to work together while keeping their identity in more complex logic designs. Communication through the intermediacy of ion signals is clearly inspired from biological processes modulated by such signals, and implemented here with ion responsive molecules. © 2014 The Royal Society of Chemistry.

Cyclization of acyl thiosemicarbazides led to new Helicobacter pylori α‐carbonic anhydrase inhibitors

The eradication of Helicobacter pylori, the etiologic agent of gastric ulcer and adenocarcinoma, is a big concern in clinics due to the increasing drug resistance phenomena and the limited number of efficacious treatment options. The exploitation of the H. pylori carbonic anhydrases (HpCAs) as promising pharmacological targets has been validated by the antibacterial activity of previously reported CA inhibitors due to the role of these enzymes in the bacterium survival in the gastric mucosa. The development of new HpCA inhibitors seems to be on the way to filling the existing antibiotics gap. Due to the recent evidence on the ability of the coumarin scaffold to inhibit microbial alpha-CAs, a large library of derivatives has been developed by means of a pH-regulated cyclization reaction of coumarin-bearing acyl thiosemicarbazide intermediates. The obtained 1,3,4-thiadiazoles (10-18a,b) and 1,2,4-triazole-3-thiones (19-26a,b) were found to strongly and selectively inhibit Hp alpha CA and computational studies were fundamental to gaining an understanding of the interaction networks governing the enzyme-inhibitor complex. Antibacterial evaluations on H. pylori ATCC 43504 highlighted some compounds that maintained potency on a resistant clinical isolate. Also, their combinations with metronidazole decreased both the minimal inhibitory concentration and minimal bactericidal concentration values of the antibiotic, with no synergistic effect

A parametric integer programming algorithm for bilevel mixed integer programs

We consider discrete bilevel optimization problems where the follower solves an integer program with a fixed number of variables. Using recent results in parametric integer programming, we present polynomial time algorithms for pure and mixed integer bilevel problems. For the mixed integer case where the leader's variables are continuous, our algorithm also detects whether the infimum cost fails to be attained, a difficulty that has been identified but not directly addressed in the literature. In this case it yields a ``better than fully polynomial time'' approximation scheme with running time polynomial in the logarithm of the relative precision. For the pure integer case where the leader's variables are integer, and hence optimal solutions are guaranteed to exist, we present two algorithms which run in polynomial time when the total number of variables is fixed.Comment: 11 page

CMS search plans and sensitivity to new physics with dijets

CMS will use dijets to search for physics beyond the standard model during early LHC running. The inclusive jet cross section as a function of jet transverse momentum, with 10 inverse picobarns of integrated luminosity, is sensitive to contact interactions beyond the reach of the Tevatron. The dijet mass distribution will be used to search for dijet resonances coming from new particles, for example an excited quark. Additional sensitivity to the existence of contact interactions or dijet resonances can be obtained by comparing dijet rates in two distinct pseudorapidity regions.Comment: 10 pages, 4 figures, accepted for publication in J. Phys. G: Nucl. Part. Phy

Searching for Lee-Wick Gauge Bosons at the LHC

In an extension of the Standard Model(SM) based on the ideas of Lee and Wick, Grinstein, O'Connell and Wise have found an interesting way to remove the usual quadratically divergent contributions to the Higgs mass induced by radiative corrections. Phenomenologically, the model predicts the existence of Terascale, negative-norm copies of the usual SM fields with rather unique properties: ghost-like propagators and negative decay widths, but with otherwise SM-like couplings. The model is both unitary and causal on macroscopic scales. In this paper we examine whether or not such states with these unusual properties can be uniquely identified as such at the LHC. We find that in the extended strong and electroweak gauge boson sector of the model, which is the simplest one to analyze, such an identification can be rather difficult. Observation of heavy gluon-like resonances in the dijet channel offers the best hope for this identification.Comment: 17 pages, 4 figs; discussion adde

Biosimilar filgrastim vs filgrastim: a multicenter nationwide observational bioequivalence study in patients with chemotherapy-induced neutropenia

Background: We studied the comparative effectiveness of biosimilar filgrastim vs original filgrastim in patients with chemotherapy-induced neutropenia.Patients and methods: This multicenter, observational study was conducted at 14 centers. The study included 337 patients experiencing neutropenia under chemotherapy. Patients were given either filgrastim 30 MIU or 48 MIU (Neupogen (R)) or biosimilar filgrastim 30 MIU (Leucostim (R)). Data regarding age, chemotherapeutic agents used, number of chemotherapy courses, previous diagnosis of neutropenia, neutrophil count of patients after treatment, medications used for the treatment of neutropenia, and duration of neutropenia were collected. Time to absolute neutrophil count (ANC) recovery was the primary efficacy measure.Results: Ambulatory and hospitalized patients comprised 11.3% and 45.1% of the enrolled patients, respectively, and a previous diagnosis of neutropenia was reported in 49.3% of the patients, as well. Neutropenia occurred in 13.7% (n=41), 45.5% (n=136), 27.4% (n=82), 11.4% (n=34), and 2.0% (n=6) of the patients during the first, second, third, fourth, and fifth cycles of chemotherapy, respectively. While the mean neutrophil count was 0.53 +/- 0.48 before treatment, a significant increase to 2.44 +/- 0.66 was observed after treatment (p=0.0001). While 90.3% of patients had a neutrophil count,1.49 before treatment, all patients had a neutrophil count >= 1.50 after treatment. Neutropenia resolved within <= 4 days of filgrastim therapy in 60.1%, 56.7%, and 52.6% of the patients receiving biosimilar filgrastim 30 MIU, original filgrastim 30 MIU, and original filgrastim 48 MIU, respectively. However, there was no significant difference between the three arms (p=0.468). Similarly, time to ANC recovery was comparable between the treatment arms (p=0.332).Conclusion: The results indicate that original filgrastim and biosimilar filgrastim have comparable efficacy in treating neutropenia. Biosimilar filgrastim provides a valuable alternative; however, there is need for further studies comparing the two products in different patient subpopulations

Public health insurance and entry into self-employment

We estimate the impact of a differential treatment of paid employees versus self-employed workers in a public health insurance system on the entry rate into entrepreneurship. In Germany, the public health insurance system is mandatory for most paid employees, but not for the selfemployed, who usually buy private health insurance. Private health insurance contributions are relatively low for the young and healthy, and until 2013 also for males, but less attractive at the other ends of these dimensions and if membership in the public health insurance allows other family members to be covered by contribution-free family insurance. Therefore, the health insurance system can create incentives or disincentives to starting up a business depending on the family’s situation and health. We estimate a discrete time hazard rate model of entrepreneurial entry based on representative household panel data for Germany, which include personal health information, and we account for non- random sample selection. We estimate that an increase in the health insurance cost differential between self-employed workers and paid employees by 100 euro per month decreases the annual probability of entry into selfemployment by 0.38 percentage points, i.e. about a third of the average annual entry rate. The results show that the phenomenon of entrepreneurship lock, which an emerging literature describes for the system of employer provided health insurance in the USA, can also occur in a public health insurance system. Therefore, entrepreneurial activity should be taken into account when discussing potential health care reforms, not only in the USA and in Germany

Differences in biological traits composition of benthic assemblages between unimpacted habitats

There is an implicit requirement under contemporary policy drivers to understand the characteristics of benthic communities under anthropogenically-unimpacted scenarios. We used a trait-based approach on a large dataset from across the European shelf to determine how functional characteristics of unimpacted benthic assemblages vary between different sedimentary habitats. Assemblages in deep, muddy environments unaffected by anthropogenic disturbance show increased proportions of downward conveyors and surface deposit-feeders, while burrowing, diffusive mixing, scavenging and predation traits assume greater numerical proportions in shallower habitats. Deep, coarser sediments are numerically more dominated by sessile, upward conveyors and suspension feeders. In contrast, unimpacted assemblages of coarse sediments in shallower regions are proportionally dominated by the diffusive mixers, burrowers, scavengers and predators. Finally, assemblages of gravelly sediments exhibit a relatively greater numerical dominance of non-bioturbators and asexual reproducers. These findings may be used to form the basis of ranking habitats along a functional sensitivity gradient