The kinematic linkage of the Dent, Craven and related faults of Northern England

New mapping of the southern part of the Dent Fault reveals three segments, each 5–6 km long, overlapping at two left-stepping zones 1–2 km wide. The main fault strands probably dip steeply WNW. A faulted footwall syncline in Carboniferous strata indicates reverse dip-slip, with a stratigraphic throw of at least 750 m. Locally developed plunging folds and imbricate fault duplexes developed at fault bends reveal a strike-slip component, indicated to be sinistral from limited slickenline data. Silurian strata in the hanging wall lack the Variscan folds observed further north. The northern overstep hosts up-faulted slivers of older Silurian and Ordovician rocks. The southern overstep zone hosts a younger faulted block compatible with releasing kinematics in sinistral strike-slip. The Dent Fault converges at its southern end with the Barbon Fault; an upfaulted wedge of Silurian strata lies between them near the branch point. The two faults swing southeastward, joining the Craven fault system via splays and linkages. Regionally, the Dent and Barbon faults form the innermost pair of a fan of ~N–S striking faults splaying off the northwest end of the South Craven–Morley-Campsall Fault System around the southwestern corner of the Askrigg Block. The kinematics of the Dent, Barbon and Craven faults fit shortening orientated NNW–SSE during late Carboniferous Variscan deformation. The rigid Askrigg Block focussed displacements around its west and south margins where fault and fold orientations were influenced by pre-existing structures, at least Acadian in age to the west and early Carboniferous to the south

RepD-mediated recruitment of PcrA helicase at the Staphylococcus aureus pC221 plasmid replication origin, oriD

Plasmid encoded replication initiation (Rep) proteins recruit host helicases to plasmid replication origins. Previously, we showed that RepD recruits directionally the PcrA helicase to the pC221 oriD, remains associated with it, and increases its processivity during plasmid unwinding. Here we show that RepD forms a complex extending upstream and downstream of the core oriD. Binding of RepD causes remodelling of a region upstream from the core oriD forming a 'landing pad' for the PcrA. PcrA is recruited by this extended RepD-DNA complex via an interaction with RepD at this upstream site. PcrA appears to have weak affinity for this region even in the absence of RepD. Upon binding of ADPNP (non-hydrolysable analogue of ATP), by PcrA, a conformational rearrangement of the RepD-PcrA-ATP initiation complex confines it strictly within the boundaries of the core oriD. We conclude that RepD-mediated recruitment of PcrA at oriD is a three step process. First, an extended RepD-oriD complex includes a region upstream from the core oriD; second, the PcrA is recruited to this upstream region and thirdly upon ATP-binding PcrA relocates within the core oriD

On the Hausdorff dimension of regular points of inviscid Burgers equation with stable initial data

Consider an inviscid Burgers equation whose initial data is a Levy a-stable process Z with a > 1. We show that when Z has positive jumps, the Hausdorff dimension of the set of Lagrangian regular points associated with the equation is strictly smaller than 1/a, as soon as a is close to 1. This gives a negative answer to a conjecture of Janicki and Woyczynski. Along the way, we contradict a recent conjecture of Z. Shi about the lower tails of integrated stable processes

Assessment of pathological response to therapy using lipid mass spectrometry imaging.

In many cancers, the establishment of a patient's future treatment regime often relies on histopathological assessment of tumor tissue specimens in order to determine the extent of the 'pathological response' to a given therapy. However, histopathological assessment of pathological response remains subjective. Here we use MALDI mass spectrometry imaging to generate lipid signatures from colorectal cancer liver metastasis specimens resected from patients preoperatively treated with chemotherapy. Using these signatures we obtained a unique pathological response score that correlates with prognosis. In addition, we identify single lipid moieties that are overexpressed in different histopathological features of the tumor, which have potential as new biomarkers for assessing response to therapy. These data show that computational methods, focusing on the lipidome, can be used to determine prognostic markers for response to chemotherapy and may potentially improve risk assessment and patient care

Imaging cellular trafficking processes in real time using lysosome targeted up-conversion nanoparticles

β-NaYF4:Yb,Gd up-conversion nanoparticles, UCNPs, surface functionalized with suitable targetting peptides function as nontoxic lysosome-specific imaging probes

Secondary somatic mutations restoring RAD51C and RAD51D associated with acquired resistance to the PARP inhibitor rucaparib in high-grade ovarian carcinoma

High-grade epithelial ovarian carcinomas (OC) containing mutated BRCA1 or BRCA2 (BRCA1/2) homologous recombination (HR) genes are sensitive to platinum-based chemotherapy and poly(ADP-ribose) polymerase inhibitors (PARPi), while restoration of HR function due to secondary mutations in BRCA1/2 has been recognized as an important resistance mechanism. We sequenced core HR pathway genes in 12 pairs of pre-treatment and post-progression tumor biopsy samples collected from patients in ARIEL2 Part 1, a phase 2 study of the PARPi rucaparib as treatment for platinum-sensitive, relapsed OC. In six of 12 pre-treatment biopsies, a truncation mutation in BRCA1, RAD51C or RAD51D was identified. In five of six paired post-progression biopsies, one or more secondary mutations restored the open reading frame. Four distinct secondary mutations and spatial heterogeneity were observed for RAD51C. In vitro complementation assays and a patient-derived xenograft (PDX), as well as predictive molecular modeling, confirmed that resistance to rucaparib was associated with secondary mutations

Majorana: from atomic and molecular, to nuclear physics

In the centennial of Ettore Majorana's birth (1906-1938?), we re-examine some aspects of his fundamental scientific production in atomic and molecular physics, including a not well known short communication. There, Majorana critically discusses Fermi's solution of the celebrated Thomas-Fermi equation for electron screening in atoms and positive ions. We argue that some of Majorana's seminal contributions in molecular physics already prelude to the idea of exchange interactions (or Heisenberg-Majorana forces) in his later workson theoretical nuclear physics. In all his papers, he tended to emphasize the symmetries at the basis of a physical problem, as well as the limitations, rather than the advantages, of the approximations of the method employed.Comment: to appear in Found. Phy

Seroprevalence and Risk Factors for Human Herpesvirus 8 Infection, Rural Egypt1

Seroprevalence and Risk Factors for Human Herpesvirus 8 Infection, Rural Egypt, Salivary and nosocomial transmission are possible

Measurement of the Bs0→J/ψKS0B_s^0\to J/\psi K_S^0 branching fraction

The $B_s^0\to J/\psi K_S^0$ branching fraction is measured in a data sample corresponding to 0.41$fb^{-1}$ of integrated luminosity collected with the LHCb detector at the LHC. This channel is sensitive to the penguin contributions affecting the sin2$\beta$ measurement from $B^0\to J/\psi K_S^0$ The time-integrated branching fraction is measured to be $BF(B_s^0\to J/\psi K_S^0)=(1.83\pm0.28)\times10^{-5}$. This is the most precise measurement to date