Srs2 Disassembles Rad51 Filaments by a Protein-Protein Interaction Triggering ATP Turnover and Dissociation of Rad51 from DNA

Rad51 is a DNA recombinase functioning in the repair of DNA double-strand breaks and the generation of genetic diversity by homologous recombination (HR). In the presence of ATP, Rad51 self-assembles into an extended polymer on single-stranded DNA to catalyze strand exchange. Inappropriate HR causes genomic instability, and it is normally prevented by remodeling enzymes that antagonize the activities of Rad51 nucleoprotein filaments. In yeast, the Srs2 helicase/translocase suppresses HR by clearing Rad51 polymers from single-stranded DNA. We have examined the mechanism of disassembly of Rad51 nucleoprotein filaments by Srs2 and find that a physical interaction between Rad51 and the C-terminal region of Srs2 triggers ATP hydrolysis within the Rad51 filament, causing Rad51 to dissociate from DNA. This allosteric mechanism explains the biological specialization of Srs2 as a DNA motor protein that antagonizes HR

Bright picosecond x‐rays from intense sub‐picosecond laser‐plasma interactions

Short‐pulse, high‐intensity laser‐plasma interactions are investigated experimentally with temporally and spectrally resolved soft x‐ray diagnostics. The emitted x‐ray spectra from solid targets of various Z are characterized for a range of laser intensities (I<5×1017 W/cm2) and pulse widths (η∼400 fs). With low contrast (105), the x‐ray spectrum in the λ=40–100 Å spectral region is dominated by line emission, and the x‐ray pulse duration is found to be long, τx≳100 ps, characteristic of a long‐scale‐length, low‐density plasma. Bright, picosecond, continuum emission, characteristic of a short‐scalelength, high‐density plasma, is produced only when a high laser contrast (1010) is used. It is demonstrated experimentally that the pulsewidth of laser‐produced x‐ray radiation may be varied down to the picosecond time‐scale by adjusting the incident ultrashort‐pulse laser flux. This controls the peak electron temperature relative to the ionization potential, corresponding to the emitted x‐ray photon energy of interest. The results are found to be consistent with the predictions of a hydrodynamics code coupled to an average atom model only if non‐local thermodynamic equilibrium (NLTE) is assumed. © 1994 American Institute of Physics.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/87587/2/473_1.pd

Control of Bright Picosecond X-Ray Emission from Intense Subpicosecond Laser-Plasma Interactions

Using temporally and spectrally resolved diagnostics, we show that the pulse duration of laser-produced soft x rays emitted from solid targets can be controlled, permitting a reduction to as short as a few picoseconds. To enable this control, only a single parameter must be adjusted, namely, the intensity of the high-contrast ultrashort laser pulse (400 fs). These results are found to be in qualitative agreement with a simple model of radiation from a collisionally dominated atomic system

Collapse of ρxx\rho_{xx} ringlike structures in 2DEGs under tilted magnetic fields

In the quantum Hall regime, the longitudinal resistivity $\rho_{xx}$ plotted as a density--magnetic-field ($n_{2D}-B$) diagram displays ringlike structures due to the crossings of two sets of spin split Landau levels from different subbands [e.g., Zhang \textit{et al.}, Phys. Rev. Lett. \textbf{95}, 216801 (2005)]. For tilted magnetic fields, some of these ringlike structures "shrink" as the tilt angle is increased and fully collapse at $\theta_c \approx 6^\circ$. Here we theoretically investigate the topology of these structures via a non-interacting model for the 2DEG. We account for the inter Landau-level coupling induced by the tilted magnetic field via perturbation theory. This coupling results in anti-crossings of Landau levels with parallel spins. With the new energy spectrum, we calculate the corresponding $n_{2D}-B$ diagram of the density of states (DOS) near the Fermi level. We argue that the DOS displays the same topology as $\rho_{xx}$ in the $n_{2D}-B$ diagram. For the ring with filling factor $\nu=4$, we find that the anti-crossings make it shrink for increasing tilt angles and collapse at a large enough angle. Using effective parameters to fit the $\theta = 0^\circ$ data, we find a collapsing angle $\theta_c \approx 3.6^\circ$. Despite this factor-of-two discrepancy with the experimental data, our model captures the essential mechanism underlying the ring collapse.Comment: 3 pages, 2 figures; Proceedings of the PASPS V Conference Held in August 2008 in Foz do Igua\c{c}u, Brazi

Day of Archaeology 2011–2017: Global Community, Public Engagement, and Digital Practice.

The Day of Archaeology (http://www.dayofarchaeology.com) was a volunteer-led international archaeological blogging event that ran from 2011 to 2017. The project asked people who define themselves as archaeologists to submit one or more blog posts about their working day on a chosen day in June or July. This article explores the history of the Day of Archaeology project and the practicalities of running a large-scale collaborative blogging project, before examining some of the topics covered in the posts. An assessment of the impact of the project follows. Overall, we hope in this work to answer some of the basic questions regarding this type of collaborative, online, global engagement – what we did, who we reached, what they talked about – and also to provide some insights for any other similar initiatives that may follow us in the future

The Nystagmus Blockage Syndrome Congenital Nystagmus, Manifest Latent Nystagmus, or Doth?

We have carefully studied, by quantitative oculography, a patient with the nystagmus blockage syndrome (NBS), and two patients with a similar disorder of eye movements that might be mistaken clinically for NBS. Our recordings revealed two distinctly different abnormalities present in a single patient with NBS. Our NBS patient exhibited congenital nystagmus (CN) waveforms when viewing at distance; the CN did not damp with convergence on a near target. When the patient allowed one eye to become esotropic, however, the nystagmus damped considerably and abruptly changed from CN to manifest latent nystagmus (MLN). This peculiar transition from CN to MLN has not been described previously. The appearance of MLN in a case with ongoing CN suggests that two different mechanisms may underlie NBS, since the only other case documented with eye movement recordings showed no transition to MLN. Because the diagnosis of NBS usually is made on evidence of clinical signs alone, it is probable that these two types have been combined indiscriminately and presented as one syndrome. In addition, our discovery of two mechanisms discernable only by quantitative recording suggests that NBS has been diagnosed inappropriately in patients with clinically similar but oculographically different eye signs. Further quantitative studies are required to fully define NBS and to determine if these are the only two mechanisms found in this syndrome. Invest Ophthalmol Vis Sci 24:1580-1587, 198

Extending the footprint record of Pareiasauromorpha to the Cisuralian : earlier appearance and wider palaeobiogeography of the group

Pareiasauromorpha is one of the most important tetrapod groups of the Permian. Skeletal evidence suggests a late Kungurian origin in North America, whereas the majority of occurrences come from the Guadalupian and Lopingian of South Africa and Russia. However, Pareiasauromorpha footprints include the ichnogenus Pachypes, which is unknown from strata older than late Guadalupian. A revision of several Pachypes-like footprints from the Cisuralian-Guadalupian of Europe and North America confirm the occurrence of this ichnogenus and of the ichnospecies Pachypes ollieri comb. nov. beginning in the Artinskian. This is the earliest known occurrence of Pachypes and it coincides with the Artinskian reptile radiation. Based on a synapomorphy-based track-trackmaker correlation, P. ollieri can be attributed to nycteroleter pareiasauromorphs such as Macroleter. Therefore, the earliest occurrences of pareiasauromorph footprints precede by at least 10 myr the earliest occurrence of this group in the skeletal record. Moreover, the palaeobiogeography of the group is extended to the Cisuralian and Guadalupian of western Europe

Automated segmentation of normal and diseased coronary arteries – The ASOCA challenge

Cardiovascular disease is a major cause of death worldwide. Computed Tomography Coronary Angiography (CTCA) is a non-invasive method used to evaluate coronary artery disease, as well as evaluating and reconstructing heart and coronary vessel structures. Reconstructed models have a wide array of for educational, training and research applications such as the study of diseased and non-diseased coronary anatomy, machine learning based disease risk prediction and in-silico and in-vitro testing of medical devices. However, coronary arteries are difficult to image due to their small size, location, and movement, causing poor resolution and artefacts. Segmentation of coronary arteries has traditionally focused on semi-automatic methods where a human expert guides the algorithm and corrects errors, which severely limits large-scale applications and integration within clinical systems. International challenges aiming to overcome this barrier have focussed on specific tasks such as centreline extraction, stenosis quantification, and segmentation of specific artery segments only. Here we present the results of the first challenge to develop fully automatic segmentation methods of full coronary artery trees and establish the first large standardized dataset of normal and diseased arteries. This forms a new automated segmentation benchmark allowing the automated processing of CTCAs directly relevant for large-scale and personalized clinical applications

Is benign MS really benign? What a meaningful classification beyond the EDSS must take into consideration

BACKGROUND: Multiple sclerosis (MS) is a neuroinflammatory and neurodegenerative disease with an unpredictable course that has a broad clinical spectrum and progresses over time. If a person with MS (PwMS) shows overall mild to moderate disability even after a long duration of disease, the term benign MS (BMS) is used. However, there is currently no generally accepted definition of BMS. Most definitions are based on EDSS in connection with disease duration, i.e. EDSS ≤3.0 after 15 years' disease duration. The question arises whether focusing on EDSS alone is adequate for classifying the disease course taking into account that 'hidden' or 'soft' symptoms are not sufficiently covered by this instrument. The aims of the study are to assess the prevalence of BMS in one of the largest patient cohorts, to describe the prevalence of patients without disabilities and to assess the further disability progression of these patients over another 15 years. METHODS: Based on data exported from the German MS Registry, PwMS with a disease duration of 15 years or more were included in the analyses. PwMS were divided into BMS (EDSS ≤3.0) or non-benign (NBMS, EDSS >3.0). RESULTS: Out of 31,824 PwMS included in the German MS Register, we identified 10,874 patients with a disease duration ≥15 years of whom 4,511 (42%) showed an EDSS ≤3.0 fulfilling the criterion of benign MS. In the subgroup with EDSS measured exactly at 15 years' disease duration, the proportion was 54%. This proportion decreased continuously with increasing disease duration and fell to 30% after 30 years. Female sex (hazard ratio [HR]: 0.84) was associated with BMS, while a progressive (HR: 2.09) and late disease onset (HR: 1.29) were associated with NBMS (p<0.001). With a more rigorous definition of BMS (EDSS ≤1.0, absence of disability, and active employment), only 580 (13%) of the initial BMS remained 'benign'. CONCLUSION: Our data propose an alternative definition (EDSS ≤1.0, absence from any disability, and the ability to work after 15 years of disease duration) which might truly reflect BMS