RasBhari: optimizing spaced seeds for database searching, read mapping and alignment-free sequence comparison

Many algorithms for sequence analysis rely on word matching or word statistics. Often, these approaches can be improved if binary patterns representing match and don't-care positions are used as a filter, such that only those positions of words are considered that correspond to the match positions of the patterns. The performance of these approaches, however, depends on the underlying patterns. Herein, we show that the overlap complexity of a pattern set that was introduced by Ilie and Ilie is closely related to the variance of the number of matches between two evolutionarily related sequences with respect to this pattern set. We propose a modified hill-climbing algorithm to optimize pattern sets for database searching, read mapping and alignment-free sequence comparison of nucleic-acid sequences; our implementation of this algorithm is called rasbhari. Depending on the application at hand, rasbhari can either minimize the overlap complexity of pattern sets, maximize their sensitivity in database searching or minimize the variance of the number of pattern-based matches in alignment-free sequence comparison. We show that, for database searching, rasbhari generates pattern sets with slightly higher sensitivity than existing approaches. In our Spaced Words approach to alignment-free sequence comparison, pattern sets calculated with rasbhari led to more accurate estimates of phylogenetic distances than the randomly generated pattern sets that we previously used. Finally, we used rasbhari to generate patterns for short read classification with CLARK-S. Here too, the sensitivity of the results could be improved, compared to the default patterns of the program. We integrated rasbhari into Spaced Words; the source code of rasbhari is freely available at http://rasbhari.gobics.de

Optimistic fair transaction processing in mobile ad-hoc networks

Mobile ad-hoc networks (MANETs) are unstable. Link errors, which are considered as an exception in fixed-wired networks must be assumed to be the default case in MANETs. Hence designing fault tolerant systems efficiently offering transactional guarantees in these unstable environments is considerably more complex. The efficient support for such guarantees is essential for business applications, e.g. for the exchange of electronic goods. This class of applications demands for transactional properties such as money and goods atomicity. Within this technical report we present an architecture, which allows for fair and atomic transaction processing in MANETs, together with an associated application that enables exchange of electronic tokens

Why are scientists not managers!?:the importance of interdisciplinary skills in business and science

Research is the translation from money to knowledge. Innovation is the metamorphosis of knowledge to money. Thus, business management and science are interdependent. That is no big news. But, in an ever faster changing economy, companies need a new type of scientist. Someone who knows not only science, but also business administration and management. Can the educational system satisfy those needs? In our opinion more work needs to be done – especially in the minds of scientists and managers alike

Genetic variation in the transforming growth factor-β1 gene is associated with susceptibility to IgA nephropathy

Background. There is growing evidence of genetic risk for susceptibility to IgA nephropathy. Among several candidate genes related to immunological regulation in renal tissue, TGFB1 is known to be a contributor to proliferation and the development of fibrosis

A systematic mapping review of the evolution of the rat Forced Swim Test: Protocols and outcome parameters

As depression is projected to become the leading mental disease burden globally by 2030, understanding the underlying pathology, as well as screening potential anti-depressants with a higher efficacy, faster onset of action, and/or fewer side-effects is essential. A commonly used test for screening novel antidepressants and studying depression-linked aspects in rodents is the Porsolt Forced Swim Test. The present systematic mappping review gives a comprehensive overview of the evolution and of the most prevalently used set-ups of this test in rats, including the choice of animals (strain, sex, and age), technical aspects of protocol and environment, as well as reported outcome measures. Additionally, we provide an accessible list of all existing publications, to support informed decision-making for procedural and technical aspects of the test, to thereby enhance reproducibility and comparability. This should further contribute to reducing the number of unnecessarily replicated experiments, and consequently, reduce the number of animals used in future

Development of a PROTAC-Based Targeting Strategy Provides a Mechanistically Unique Mode of Anti-Cytomegalovirus Activity

Human cytomegalovirus (HCMV) is a major pathogenic herpesvirus that is prevalent worldwide and it is associated with a variety of clinical symptoms. Current antiviral therapy options do not fully satisfy the medical needs; thus, improved drug classes and drug-targeting strategies are required. In particular, host-directed antivirals, including pharmaceutical kinase inhibitors, might help improve the drug qualities. Here, we focused on utilizing PROteolysis TArgeting Chimeras (PROTACs), i.e., hetero-bifunctional molecules containing two elements, namely a target-binding molecule and a proteolysis-inducing element. Specifically, a PROTAC that was based on a cyclin-dependent kinase (CDK) inhibitor, i.e., CDK9-directed PROTAC THAL-SNS032, was analyzed and proved to possess strong anti-HCMV AD169-GFP activity, with values of EC50 of 0.030 µM and CC50 of 0.175 µM (SI of 5.8). Comparing the effect of THAL-SNS032 with its non-PROTAC counterpart SNS032, data indicated a 3.7-fold stronger anti-HCMV efficacy. This antiviral activity, as illustrated for further clinically relevant strains of human and murine CMVs, coincided with the mid-nanomolar concentration range necessary for a drug-induced degradation of the primary (CDK9) and secondary targets (CDK1, CDK2, CDK7). In addition, further antiviral activities were demonstrated, such as the inhibition of SARS-CoV-2 replication, whereas other investigated human viruses (i.e., varicella zoster virus, adenovirus type 2, and Zika virus) were found insensitive. Combined, the antiviral quality of this approach is seen in its (i) mechanistic uniqueness; (ii) future options of combinatorial drug treatment; (iii) potential broad-spectrum activity; and (iv) applicability in clinically relevant antiviral models. These novel data are discussed in light of the current achievements of anti-HCMV drug development

Amphiphilic Copolymers for Versatile, Facile, and In Situ Tunable Surface Biofunctionalization

Precision surface engineering is key to advanced biomaterials. A new platform of PEGylated styrene-maleic acid copolymers for adsorptive surface biofunctionalization is reported. Balanced amphiphilicity renders the copolymers water-soluble but strongly affine for surfaces. Fine-tuning of their molecular architecture provides control over adsorptive anchorage onto specific materials-which is why they are referred to as "anchor polymers" (APs)-and over structural characteristics of the adsorbed layers. Conjugatable with an array of bioactives-including cytokine-complexing glycosaminoglycans, cell-adhesion-mediating peptides and antimicrobials-APs can be applied to customize materials for demanding biotechnologies in uniquely versatile, simple, and robust ways. Moreover, homo- and heterodisplacement of adsorbed APs provide unprecedented means of in situ alteration and renewal of the functionalized surfaces. The related options are exemplified with proof-of-concept experiments of controlled bacterial adhesion, human umbilical vein endothelial cell, and induced pluripotent cell growth on AP-functionalized surfaces