Arabidopsis Sec1/Munc18 protein SEC11 is a competitive and dynamic modulator of SNARE binding and SYP121-dependent vesicle traffic

The Arabidopsis thaliana Qa-SNARE SYP121 (=SYR1/PEN1) drives vesicle traffic at the plasma membrane of cells throughout the vegetative plant. It facilitates responses to drought, to the water stress hormone abscisic acid, and to pathogen attack, and it is essential for recovery from so-called programmed stomatal closure. How SYP121-mediated traffic is regulated is largely unknown, although it is thought to depend on formation of a fusion-competent SNARE core complex with the cognate partners VAMP721 and SNAP33. Like SYP121, the Arabidopsis Sec1/Munc18 protein SEC11 (=KEULE) is expressed throughout the vegetative plant. We find that SEC11 binds directly with SYP121 both in vitro and in vivo to affect secretory traffic. Binding occurs through two distinct modes, one requiring only SEC11 and SYP121 and the second dependent on assembly of a complex with VAMP721 and SNAP33. SEC11 competes dynamically for SYP121 binding with SNAP33 and VAMP721, and this competition is predicated by SEC11 association with the N terminus of SYP121. These and additional data are consistent with a model in which SYP121-mediated vesicle fusion is regulated by an unusual “handshaking” mechanism of concerted SEC11 debinding and rebinding. They also implicate one or more factors that alter or disrupt SEC11 association with the SYP121 N terminus as an early step initiating SNARE complex formation

Kappa symmetry, generalized calibrations and spinorial geometry

We extend the spinorial geometry techniques developed for the solution of supergravity Killing spinor equations to the kappa symmetry condition for supersymmetric brane probe configurations in any supergravity background. In particular, we construct the linear systems associated with the kappa symmetry projector of M- and type II branes acting on any Killing spinor. As an example, we show that static supersymmetric M2-brane configurations which admit a Killing spinor representing the SU(5) orbit of $Spin(10,1)$ are generalized almost hermitian calibrations and the embedding map is pseudo-holomorphic. We also present a bound for the Euclidean action of M- and type II branes embedded in a supersymmetric background with non-vanishing fluxes. This leads to an extension of the definition of generalized calibrations which allows for the presence of non-trivial Born-Infeld type of fields in the brane actions.Comment: 9 pages, latex, references added and minor change

A Novel Adaptation of a Parent-Child Observational Assessment Tool for Appraisals and Coping in Children Exposed to Acute Trauma

Background: Millions of children worldwide are exposed to acute potentially traumatic events (PTEs) annually. Many children and their families experience significant emotional distress and/or functional impairment following PTEs. While current research has begun to highlight a role for early appraisals and coping in promoting or preventing full recovery from PTEs, the exact nature of the relationships among appraisals, coping, and traumatic stress reactions as well as how appraisals and coping behaviors are influenced by the child\u27s environment (e.g., parents) remains unclear; assessment tools that reach beyond self-report are needed to improve this understanding. Objective: The objective of the current study is to describe the newly created Trauma Ambiguous Situations Tool (TAST; i.e., an observational child–parent interview and discussion task that allows assessment of appraisals, coping, and parent–child processes) and to report on initial feasibility and validation of TAST implemented with child–parent dyads in which children were exposed to a PTE. Method: As part of a larger study on the role of biopsychosocial factors in posttraumatic stress reactions, children (aged 8–13) and parents (n=25 child–parent dyads) completed the TAST during the child\u27s hospitalization for injury. Results: Children and parents engaged well with the TAST. The time to administer the TAST was feasible, even in a peri-trauma context. The TAST solicited a wide array of appraisals (threat and neutral) and coping solutions (proactive and avoidant). Forced-choice and open-ended appraisal assessments provided unique information. The parent–child discussion portion of the TAST allowed for direct observation of parent–child processes and demonstrated parental influence on children\u27s appraisals and coping solutions. Conclusions: The TAST is a promising new research tool, which may help to explicate how parents influence their child\u27s developing appraisals and coping solutions following a PTE. More research should examine the relationships of appraisals, coping, and parent–child processes assessed by the TAST with traumatic stress outcomes

Climate fluctuations and the spring invasion of the North Sea by Calanus finmarchicus

The population of Calanus finmarchicus in the North Sea is replenished each spring by invasion from an overwintering stock located beyond the shelf edge. A combincation of field observations, statistical analysis of Continuous Plankton Recorder (CPR) data, and particle tracking model simulations, was used to investigate the processes involved in the cross-shelf invasion. The results showed that the main source of overwintering animals entering the North Sea in the spring is at depths of greater than 600m in the Faroe Shetland Channel, where concentrations of up to 620m -3 are found in association with the overflow of Norwegian Sea Deep Water (NSDW) across the Iceland Scotland Ridge. The input of this water mass to the Faroe Shetland Channel, and hence the supply of overwintering C. finmarchicus, has declined since the late 1960s due to changes in convective processes in the Greenland Sea. Beginning in February, animals start to emerge from the overwintering state and migrate to the surface waters, where their transport into the North Sea is mainly determined by the incidence of north-westerly winds that have declined since the 1960s. Together, these two factors explain a high proportion of the 30-year trends in spring abundance in the North Sea as measured by the CPR survey. Both the regional winds and the NSDW overflow are connected to the North Atlantic Oscillation Index (NAO), which is an atmospheric climate index, but with different time scales of response. Thus, interannual fluctuations in the NAO can cause immediate changes in the incidence of north-westerly winds without leading to corresponding changes in C. finmarchicus abundance in the North Sea, because the NSDW overflow responds over longer (decadal) time scales

Orientifolds of K3 and Calabi-Yau Manifolds with Intersecting D-branes

We investigate orientifolds of type II string theory on K3 and Calabi-Yau 3-folds with intersecting D-branes wrapping special Lagrangian cycles. We determine quite generically the chiral massless spectrum in terms of topological invariants and discuss both orbifold examples and algebraic realizations in detail. Intriguingly, the developed techniques provide an elegant way to figure out the chiral sector of orientifold models without computing any explicit string partition function. As a new example we derive a non-supersymmetric Standard-like Model from an orientifold of type IIA on the quintic Calabi-Yau 3-fold with wrapped D6-branes. In the case of supersymmetric intersecting brane models on Calabi-Yau manifolds we discuss the D-term and F-term potentials, the effective gauge couplings and the Green-Schwarz mechanism. The mirror symmetric formulation of this construction is provided within type IIB theory. We finally include a short discussion about the lift of these models from type IIB on K3 to F-theory and from type IIA on Calabi-Yau 3-folds to M-theory on G_2 manifolds.Comment: 82 pages, harvmac, 5 figures. v2: references added. v3: T^6 orientifold corrected, JHEP versio

D-Brane Probes of Special Holonomy Manifolds

Using D2-brane probes, we study various properties of M-theory on singular, non-compact manifolds of G_2 and Spin(7) holonomy. We derive mirror pairs of N=1 supersymmetric three-dimensional gauge theories, and apply this technique to realize exceptional holonomy manifolds as both Coulomb and Higgs branches of the D2-brane world-volume theory. We derive a ``G_2 quotient construction'' of non-compact manifolds which admit a metric of G_2 holonomy. We further discuss the moduli space of such manifolds, including the structure of geometrical transitions in each case. For completeness, we also include familiar examples of manifolds with SU(3) and Sp(2) holonomy, where some of the new ideas are clarified and tested.Comment: 79 pages, Late

Impact of alcohol use disorder severity on human immunodeficiency virus (HIV) viral suppression and CD4 count in three international cohorts of people with HIV.

Alcohol use has been linked to worse human immunodeficiency virus (HIV) immunologic/virologic outcomes, yet few studies have explored the effects of alcohol use disorder (AUD). This study assessed whether AUD severity is associated with HIV viral suppression and CD4 count in the three cohorts of the Uganda Russia Boston Alcohol Network for Alcohol Research Collaboration on HIV/AIDS (URBAN ARCH) Consortium. People with HIV (PWH) in Uganda (n = 301), Russia (n = 400), and Boston (n = 251), selected in-part based on their alcohol use, were included in analyses. Logistic and linear regressions were used to assess the cross-sectional associations between AUD severity (number of DSM-5 diagnostic criteria) and (1) HIV viral suppression, and (2) CD4 count (cells/mm <sup>3</sup> ) adjusting for covariates. Analyses were conducted separately by site. The proportion of females was 51% (Uganda), 34% (Russia), and 33% (Boston); mean age (SD) was 40.7 (9.6), 38.6 (6.3), and 52.1 (10.5), respectively. All participants in Uganda and all but 27% in Russia and 5% in Boston were on antiretroviral therapy. In Uganda, 32% met criteria for AUD, 92% in Russia, and 43% in Boston. The mean (SD) number of AUD criteria was 1.6 (2.4) in Uganda, 5.6 (3.3) in Russia, and 2.4 (3.1) in Boston. Most participants had HIV viral suppression (Uganda 92%, Russia 57%, Boston 87%); median (IQR) CD4 count was 673 (506, 866), 351 (201, 542), and 591 (387, 881), respectively. In adjusted models, there were no associations between AUD severity and HIV viral suppression: adjusted odds ratios (AOR) (95%CI) per 1 additional AUD criterion in Uganda was 1.08 (0.87, 1.33); Russia 0.98 (0.92, 1.04); and Boston 0.95 (0.84, 1.08) or CD4 count: mean difference (95%CI) per 1 additional criterion: 5.78 (-7.47, 19.03), -3.23 (-10.91, 4.44), and -8.18 (-24.72, 8.35), respectively. In three cohorts of PWH, AUD severity was not associated with HIV viral suppression or CD4 count. PWH with AUD in the current era of antiretroviral therapy can achieve virologic control

The K-theoretic Farrell-Jones Conjecture for hyperbolic groups

We prove the K-theoretic Farrell-Jones Conjecture for hyperbolic groups with (twisted) coefficients in any associative ring with unit.Comment: 33 pages; final version; to appear in Invent. Mat

The Complexity of the Empire Colouring Problem

We investigate the computational complexity of the empire colouring problem (as defined by Percy Heawood in 1890) for maps containing empires formed by exactly $r > 1$ countries each. We prove that the problem can be solved in polynomial time using $s$ colours on maps whose underlying adjacency graph has no induced subgraph of average degree larger than $s/r$. However, if $s \geq 3$, the problem is NP-hard even if the graph is a forest of paths of arbitrary lengths (for any $r \geq 2$, provided $s < 2r - \sqrt(2r + 1/4+ 3/2)$. Furthermore we obtain a complete characterization of the problem's complexity for the case when the input graph is a tree, whereas our result for arbitrary planar graphs fall just short of a similar dichotomy. Specifically, we prove that the empire colouring problem is NP-hard for trees, for any $r \geq 2$, if $3 \leq s \leq 2r-1$ (and polynomial time solvable otherwise). For arbitrary planar graphs we prove NP-hardness if $s<7$ for $r=2$, and $s < 6r-3$, for $r \geq 3$. The result for planar graphs also proves the NP-hardness of colouring with less than 7 colours graphs of thickness two and less than $6r-3$ colours graphs of thickness $r \geq 3$.Comment: 23 pages, 12 figure

Program Repair Suggestions from Graphical State-Transition Specifications

Abstract. In software engineering, graphical formalisms, like state-transition tables and automata, are very often indispensable parts of the specifications. Such a formalism usually leads to specification re-finement that maintains the simulation/bisimulation relation between an implementation and a specification. We investigate how to use formal techniques to generate suggestions for repairing a program that breaks the bisimulation relation with a graphical specification. We use state graphs as a unified representation of the program models and specifica-tions. We propose a technique that may evaluate the cost of a repair. We present a PTIME heuristic algorithm that suggests how to repair a model state graph. We then explain how to derive repair suggestions for programs from the repair for state graphs. Finally, we report our experi-ment that checks the performance of our repair algorithms and the costs of our repairs. Key words: state graph, state transition relation, repair, graph theory, cost, evaluation, equivalence, bisimulation