Parallel Computing with Low-Cost FPGAs A Framework for COPACOBANA

In many disciplines such as applied sciences or computer science, computationally challenging problems demand for extraordinary computing power, mostly provided by super computers or clusters of conventional desktop CPUs. During the last decades, several flavors of super computers have evolved, most of which are suitable for a specific type of problem. In general, dedicated clusters and super computers suffer from their extremely high cost per computation and are, due to the lack of cheap alternatives, currently the only possible solution to computational hard problems. More recently, emerging low-cost FPGAs tend to be a very cost-effective alternative to conventional CPUs for solving at least some of the computational hard problems such as those appearing in cryptanalysis and bio-informatics. In cryptanalysis, breaking symmetric or asymmetric ciphers is computationally extremely demanding. Since the security parameters (in particular the key length) of almost all practical crypto algorithms are chosen such that attacks with conventional computers are computationally infeasible, the only promising way to tackle existing ciphers (assuming no mathematical breakthrough) is to build special-purpose hardware. Dedicating those machines to the task of cryptanalysis holds the promise of a dramatically improved cost-performance ratio so tha

Homologous chromosomes are stably conjoined for Drosophila male meiosis I by SUM, a multimerized protein assembly with modules for DNA-binding and for separase-mediated dissociation co-opted from cohesin.

For meiosis I, homologous chromosomes must be paired into bivalents. Maintenance of homolog conjunction in bivalents until anaphase I depends on crossovers in canonical meiosis. However, instead of crossovers, an alternative system achieves homolog conjunction during the achiasmate male meiosis of Drosophila melanogaster. The proteins SNM, UNO and MNM are likely constituents of a physical linkage that conjoins homologs in D. melanogaster spermatocytes. Here, we report that SNM binds tightly to the C-terminal region of UNO. This interaction is homologous to that of the cohesin subunits stromalin/Scc3/STAG and α-kleisin, as revealed by sequence similarities, structure modeling and cross-link mass spectrometry. Importantly, purified SU_C, the heterodimeric complex of SNM and the C-terminal region of UNO, displayed DNA-binding in vitro. DNA-binding was severely impaired by mutational elimination of positively charged residues from the C-terminal helix of UNO. Phenotypic analyses in flies fully confirmed the physiological relevance of this basic helix for chromosome-binding and homolog conjunction during male meiosis. Beyond DNA, SU_C also bound MNM, one of many isoforms expressed from the complex mod(mdg4) locus. This binding of MNM to SU_C was mediated by the MNM-specific C-terminal region, while the purified N-terminal part common to all Mod(mdg4) isoforms multimerized into hexamers in vitro. Similarly, the UNO N-terminal domain formed tetramers in vitro. Thus, we suggest that multimerization confers to SUM, the assemblies composed of SNM, UNO and MNM, the capacity to conjoin homologous chromosomes stably by the resultant multivalent DNA-binding. Moreover, to permit homolog separation during anaphase I, SUM is dissociated by separase, since UNO, the α-kleisin-related protein, includes a separase cleavage site. In support of this proposal, we demonstrate that UNO cleavage by tobacco etch virus protease is sufficient to release homolog conjunction in vivo after mutational exchange of the separase cleavage site with that of the bio-orthogonal protease

The Kinetochore Proteins Pcs1 and Mde4 and Heterochromatin Are Required to Prevent Merotelic Orientation

BACKGROUND: Accurate chromosome segregation depends on the establishment of correct-amphitelic-kinetochore orientation. Merotelic kinetochore orientation is an error that occurs when a single kinetochore attaches to microtubules emanating from opposite spindle poles, a condition that hinders segregation of the kinetochore to a spindle pole in anaphase. To avoid chromosome missegregation resulting from merotelic kinetochore orientation, cells have developed mechanisms to prevent or correct merotelic attachment. A protein called Pcs1 has been implicated in preventing merotelic attachment in mitosis and meiosis II in the fission yeast S. pombe. RESULTS: We report that Pcs1 forms a complex with a protein called Mde4. Both Pcs1 and Mde4 localize to the central core of centromeres. Deletion of mde4(+), like that of pcs1(+), causes the appearance of lagging chromosomes during the anaphases of mitotic and meiosis II cells. We provide evidence that the kinetochores of lagging chromosomes in both pcs1 and mde4 mutant cells are merotelically attached. In addition, we find that lagging chromosomes in cells with defective centromeric heterochromatin also display features consistent with merotelic attachment. CONCLUSIONS: We suggest that the Pcs1/Mde4 complex is the fission yeast counterpart of the budding yeast monopolin subcomplex Csm1/Lrs4, which promotes the segregation of sister kinetochores to the same pole during meiosis I. We propose that the Pcs1/Mde4 complex acts in the central kinetochore domain to clamp microtubule binding sites together, the centromeric heterochromatin coating the flanking domains provides rigidity, and both systems contribute to the prevention of merotelic attachment

SNM and UNO_C form a stable heterodimeric complex.

(A) SNM and UNO_C, with N-terminally fused maltose-binding protein (MBP) and twin Strep-II affinity tag (Stag), respectively, form a stable SU_C complex. Size exclusion chromatography profile from the final purification step and Coomassie-stained gel for analysis of the indicated peak are shown. (B) Mass photometry analysis of SU_C. The indicated molecular mass was determined by a Gaussian fit of the distribution of counts calibrated against a molecular mass standard. (C) SEC-MALS analysis of SU_C, revealing the indicated molecular mass. (D) AF2 model of SU_C with predicted alignment plot on the right. Regions associated with high (30 Å) and low (0 Å) error as predicted by the algorithm are shown in red and blue, respectively. (E) Analysis of SU_C by cross-linking mass spectrometry (XL-MS). The observed cross-links (with false discovery rate 74], with separation distance of cross-linked positions color-coded. A plot with the distance distribution of the observed cross-links mapped to the AF2 model is presented on the right. The majority of cross-links fall within the distance range expected for the DSBU linker (~27 Å, see text and [42]. The longer distance outliers may be caused by errors in the model prediction, or flexibility within the structure.</p