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Background Parental difficulties, including mental ill health, substance misuse, domestic violence and learning disability have been associated with children entering out-of-home care. There is also evidence that these issues may co-occur within families. Understanding how the co-occurrence of these difficulties is associated with care entry is complex because they may co-occur in the same or different household members and have different impacts on the likelihood of care entry when they occur in mothers, fathers or in single parent households. Method Administrative data from local authority children’s services in Wales were linked with demographic data to identify households in which children lived prior to entering care. Linkage to birth data identified biological mothers. Linkage with primary care, emergency department, hospital admissions and substance misuse services data enabled indicators of substance misuse, mental health, assaults in the home, learning disability and neurodivergence in the adults in those households to be identified. A series of multilevel binary logistic regression models were used to explore the odds of a household having one or more children entering care if risk factors were present. These considered the effects of individual risks, and cumulative risk both in individual adults in the household, and across the whole household. The effects of the number of adults, having adults with no risks and the differential impacts of risks in biological mothers, other women or men were also explored. Additional models explored these factors in single adult households. Results Cumulative risks increased the likelihood of care entry, however this effect disappeared when individual risks were controlled for. The presence of an individual with no risks in the household acted as a protective factor. Overall, the impact of the risks on the odds of care entry was substantially greater if the risks were present in the biological mother than if they occurre

Contains fulltext : 248793.pdf (Publisher’s version ) (Open Access)

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The InSight lander rests on a regolith-covered, Hesperian to Early Amazonian lava plain in Elysium Planitia within a ∼27-m-diameter, degraded impact crater called Homestead hollow. The km to cm-scale stratigraphy beneath the lander is relevant to the mission's geophysical investigations. Geologic mapping and crater statistics indicate that ∼170 m of mostly Hesperian to Early Amazonian basaltic lavas are underlain by Noachian to Early Hesperian (∼3.6 Ga) materials of possible sedimentary origin. Up to ∼140 m of this volcanic resurfacing occurred in the Early Amazonian at 1.7 Ga, accounting for removal of craters ≤700 m in diameter. Seismic data however, suggest a clastic horizon that interrupts the volcanic sequence between depths of ∼30 and ∼75 m. Meter-scale stratigraphy beneath the lander is constrained by local and regional regolith thickness estimates that indicate up to 10–30 m of coarse-grained, brecciated regolith that fines upwards to a ∼3 m thick loosely-consolidated, sand-dominated unit. The maximum depth of Homestead hollow, at ∼3 m, indicates that the crater is entirely embedded in regolith. The hollow is filled by sand-size eolian sediments, with contributions from sand to cobble-size slope debris, and sand to cobble-size ejecta. Lander-based observations indicate that the fill at Homestead hollow contains a cohesive layer down to ∼10–20 cm depth that is visible in lander rocket-excavated pits and the HP3 mole hole. The surface of the landing site is capped by a ∼1 to 2 cm-thick loosely granular, sand-sized layer with a microns-thick surficial dust horizon.

Rocks around the InSight lander were measured in lander orthoimages of the near field (<10 m), in panoramas of the far field (<40 m), and in a high-resolution orbital image around the lander (1 km²). The cumulative fractional area versus diameter size-frequency distributions for four areas in the near field fall on exponential model curves used for estimating hazards for landing spacecraft. The rock abundance varies in the near field from 0.6% for the sand and pebble rich area to the east within Homestead hollow, to ~3-5% for the progressively rockier areas to the south, north and west. The rock abundance of the entire near field is just over 3%, which falls between that at the Phoenix (2%) and Spirit (5%) landing sites. Rocks in the far field (<40 m) that could be identified in both the surface panorama and a high-resolution orbital image fall on the same exponential model curve as the average near field rocks. Rocks measured in a high-resolution orbital image (27.5 cm/pixel) within ~500 m of the lander that includes several rocky ejecta craters fall on 4-5% exponential model curves, similar to the northern and western near field areas. As a result, the rock abundances observed from orbit falls on the same exponential model rock abundance curves as those viewed from the surface. These rock abundance measurements around the lander are consistent with thermal imaging estimates over larger pixel areas as well as expectations from fragmentation theory of an impacted Amazonian/Hesperian lava flow.

Rock heights and three-dimensional shapes around the InSight lander in Homestead hollow, Mars, provide new constraints on modification of the degraded 27 m in diameter impact crater and are a tool for characterizing degradation on regolith-covered lava plains on Mars. Decreasing average rock height and increasing percentage of fragments where height comprises the short axis from outside to within the hollow supports significant ejecta deflation accompanied by infilling of the interior. Rock relief outside the hollow is compared with expectations of pristine ejecta thickness and indicates up to ~40 cm of near-rim early deflation (decreasing to a few cm out to one diameter) can account for the predicted eolian component of infilling and that other eolian infilling sources are not required. Scattered rocks in the hollow are ejecta from subsequent nearby impacts and their mostly buried expression is consistent with subsequent long-term degradation estimated to be 10⁻⁴ m/Myr. Basalt rock shapes at InSight are likely similar to basalt rock shapes on Earth, but appear more platy, bladed, and elongate in a triangular form factor plot and more discoidal and bladed in an axes ratio plot. Nevertheless, addition of 10 cm to near rim rock heights to account for continued partial embedding in ejecta would result in rock shapes quite similar to terrestrial rocks. Consistency between degradation estimates based on current rock relief and rock shape after accounting for partial embedding in ejecta indicates up to ~30-40 cm early (~0.1 Ga) near-rim deflation was followed by much lesser long-term degradation.

Hepatitis B virus (HBV) is a major human pathogen that causes liver diseases. The main HBV RNAs are unspliced transcripts that encode the key viral proteins. Recent studies have shown that some of the HBV spliced transcript isoforms are predictive of liver cancer, yet the roles of these spliced transcripts remain elusive. Furthermore, there are nine major HBV genotypes common in different regions of the world, these genotypes may express different spliced transcript isoforms. To systematically study the HBV splice variants, we transfected human hepatoma cells, Huh7, with four HBV genotypes (A2, B2, C2 and D3), followed by deep RNA-sequencing. We found that 13-28 % of HBV RNAs were splice variants, which were reproducibly detected across independent biological replicates. These comprised 6 novel and 10 previously identified splice variants. In particular, a novel, singly spliced transcript was detected in genotypes A2 and D3 at high levels. The biological relevance of these splice variants was supported by their identification in HBV-positive liver biopsy and serum samples, and in HBV-infected primary human hepatocytes. Interestingly the levels of HBV splice variants varied across the genotypes, but the spliced pregenomic RNA SP1 and SP9 were the two most abundant splice variants. Counterintuitively, these singly spliced SP1 and SP9 variants had a suboptimal 5' splice site, supporting the idea that splicing of HBV RNAs is tightly controlled by the viral post-transcriptional regulatory RNA element.

The clinical sequelae associated with chronic HBV infection is generally regarded as a consequence of an inadequate and inappropriate immune response to active viral replication, predominantly at the T-cell level. However, recent studies on hepatitis B surface antigen (HBsAg)-specific B cells and hepatitis B surface antibody (anti-HB) responses have identified their previously unrecognized role in the pathogenesis of chronic hepatitis B (CHB). These studies have also uncovered novel therapeutic approaches to more effectively target HBsAg loss and seroconversion, an important end point and regarded as a functional cure. Anti-HBs IgG has also been shown to have multiple direct acting antiviral roles with the Fab component directly blocking viral entry, and release while the Fc component has been linked to antibody dependent cellular cytotoxicity. Likewise, the HBsAg-specific B-cell dysfunctionality can be reversed providing new therapeutic opportunities to achieve functional cure in CHB.

The Interior Exploration using Seismic Investigations, Geodesy and Heat Transport (InSight) spacecraft landed successfully on Mars and imaged the surface to characterize the surficial geology. Here we report on the geology and subsurface structure of the landing site to aid in situ geophysical investigations. InSight landed in a degraded impact crater in Elysium Planitia on a smooth sandy, granule- and pebble-rich surface with few rocks. Superposed impact craters are common and eolian bedforms are sparse. During landing, pulsed retrorockets modified the surface to reveal a near surface stratigraphy of surficial dust, over thin unconsolidated sand, underlain by a variable thickness duricrust, with poorly sorted, unconsolidated sand with rocks beneath. Impact, eolian, and mass wasting processes have dominantly modified the surface. Surface observations are consistent with expectations made from remote sensing data prior to landing indicating a surface composed of an impact-fragmented regolith overlying basaltic lava flows.

BACKGROUND: An impaired HBsAg-secretion can increase HBV oncogenic-properties. Here, we investigate genetic-determinants in HBsAg correlated with HBV-induced hepatocellular carcinoma (HCC), and their impact on HBsAg-secretion and cell-proliferation. METHODS: This study included 128 chronically HBV-infected patients: 23 with HCC (73.9% D; 26.1% A HBV-genotype), and 105 without cirrhosis/HCC (72.4% D, 27.6% A) as reference-group. The impact of mutations on HBsAg-secretion was assessed by measuring the ratio [secreted/intracellular HBsAg] until day 5 post-transfection. The impact of mutations on cell-cycle advancement was assessed by flow-cytometry. RESULTS: Two HBsAg mutations significantly correlated with HCC: P203Q (17.4% [4/23] in HCC vs 1.0% [1/105] in non-HCC, P=0.004); S210R (34.8% [8/23] in HCC vs 3.8% [4/105] in non-HCC, P <0.001); P203Q+S210R (17.4% [4/23] in HCC vs 0% [0/110] in non-HCC, P=0.001). Both mutations reside in trans-membrane C-terminal domain critical for HBsAg-secretion. In in-vitro experiments, P203Q, S210R and P203Q+S210R significantly reduced the ratio [secreted/intracellular HBsAg] compared to wt at each time-point analysed (P <0.05), supporting an impaired HBsAg-secretion. Furthermore, P203Q and P203Q+S210R increased the percentage of cells in S-phase compared to wt, indicating cell-cycle progression (P203Q:26±13%; P203Q+S210R:29±14%; wt:18%±9, P <0.01. Additionally, S210R increased the percentage of cells in G2/M-phase (26±8% for wt versus 33±6% for S210R, P <0.001). CONCLUSIONS: Specific mutations in HBsAg C-terminus significantly correlate with HBV-induced HCC. They hamper HBsAg-secretion and are associated with increased cellular proliferation, supporting their involvement in HCC-development. The identification of viral genetic markers associated with HCC is critical to identify patients at higher HCC-risk that may deserve intensive liver monitoring, and/or early anti-HBV therapy.

© The Author(s) 2016.Spacecraft exploring Mars such as the Mars Exploration Rovers Spirit and Opportunity, as well as the Mars Science Laboratory or Curiosity rover, have accumulated evidence for wet and habitable conditions on early Mars more than 3 billion years ago. Current conditions, by contrast, are cold, extremely arid and seemingly inhospitable. To evaluate exactly how dry today's environment is, it is important to understand the ongoing current weathering processes. Here we present chemical weathering rates determined for Mars. We use the oxidation of iron in stony meteorites investigated by the Mars Exploration Rover Opportunity at Meridiani Planum. Their maximum exposure age is constrained by the formation of Victoria crater and their minimum age by erosion of the meteorites. The chemical weathering rates thus derived are ~1 to 4 orders of magnitude slower than that of similar meteorites found in Antarctica where the slowest rates are observed on Earth.

Abstract This review summarizes the use of High Resolution Stereo Camera (HRSC) data as an instrumental tool and its application in the analysis of geological processes and landforms on Mars during the last 10 years of operation. High-resolution digital elevations models on a local to regional scale are the unique strength of the HRSC instrument. The analysis of these data products enabled quantifying geological processes such as effusion rates of lava flows, tectonic deformation, discharge of water in channels, formation timescales of deltas, geometry of sedimentary deposits as well as estimating the age of geological units by crater size-frequency distribution measurements. Both the quantification of geological processes and the age determination allow constraining the evolution of Martian geologic activity in space and time. A second major contribution of HRSC is the discovery of episodicity in the intensity of geological processes on Mars. This has been revealed by comparative age dating of volcanic, fluvial, glacial, and lacustrine deposits. Volcanic processes on Mars have been active over more than 4 Gyr, with peak phases in all three geologic epochs, generally ceasing towards the Amazonian. Fluvial and lacustrine activity phases spread a time span from Noachian until Amazonian times, but detailed studies show that they have been interrupted by multiple and long lasting phases of quiescence. Also glacial activity shows discrete phases of enhanced intensity that may correlate with periods of increased spin-axis obliquity. The episodicity of geological processes like volcanism, erosion, and glaciation on Mars reflects close correlation between surface processes and endogenic activity as well as orbit variations and changing climate condition.

© 2014 John Wiley & Sons, Inc. The different branches of the Wnt signaling pathway were first characterized in developmental contexts, but in recent times, each branch has been implicated in tumor growth and progression. This chapter exemplifies this link between development and cancer by focusing on two Wnt-driven cancers, colorectal cancer (CRC) and hepatocellular carcinoma (HCC). It focuses on the processes of epithelial-to-mesenchymal transition (EMT) and the reverse transition, mesenchymal-to-epithelial transition (MET), both fundamental mechanisms of tumor metastasis and morphogenesis. HCC shares many parallels with CRC with respect to the involvement of Wnt signaling in cancer initiation and progression.

We describe and study families of BPS microstate geometries, namely, smooth, horizonless asymptotically-flat solutions to supergravity. We examine these solutions from the perspective of earlier attempts to find solitonic solutions in gravity and show how the microstate geometries circumvent the earlier "No-Go" theorems. In particular, we re-analyse the Smarr formula and show how it must be modified in the presence of non-trivial second homology. This, combined with the supergravity Chern-Simons terms, allows the existence of rich classes of BPS, globally hyperbolic, asymptotically flat, microstate geometries whose spatial topology is the connected sum of N copies of S^2 x S^2 with a "point at infinity" removed. These solutions also exhibit "evanescent ergo-regions," that is, the non-space-like Killing vector guaranteed by supersymmetry is time-like everywhere except on time-like hypersurfaces (ergo-surfaces) where the Killing vector becomes null. As a by-product of our work, we are able to resolve the puzzle of why some regular soliton solutions violate the BPS bound: their spactimes do not admit a spin structure., Comment: 55 pages, 2 figures

Entecavir (ETV) exhibits potent antiviral activity in patients chronically infected with wild-type or lamivudine (3TC)-resistant (3TCr) hepatitis B virus (HBV). Among the patients treated in phase II ETV clinical trials, two patients for whom previous therapies had failed exhibited virologic breakthrough while on ETV. Isolates from these patients (arbitrarily designated patients A and B) were analyzed genotypically for emergent substitutions in HBV reverse transcriptase (RT) and phenotypically for reduced susceptibility in cultures and in HBV polymerase assays. After 54 weeks of 3TC therapy, patient A (A1463901-A) received 0.5 mg of ETV for 52 weeks followed by a combination of ETV and 100 mg of 3TC for 89 weeks. Viral rebound occurred at 133 weeks after ETV was started. The 3TCr RT substitutions rtV173L, rtL180M, and rtM204V were present at study entry, and the additional substitutions rtI169T and rtM250V emerged during ETV-3TC combination treatment. Reduced ETV susceptibility in vitro required the rtM250V substitution in addition to the 3TCr substitutions. For liver transplant patient B (AI463015-B), previous famciclovir, ganciclovir, foscarnet, and 3TC therapies had failed, and RT changes rtS78S/T, rtV173L, rtL180M, rtT184S, and rtM204V were present at study entry. Viral rebound occurred after 76 weeks of therapy with ETV at 1.0 mg, with the emergence of rtT184G, rtI169T, and rtS202I substitutions within the preexisting 3TCr background. Reduced susceptibility in vitro was highest when both the rtT184G and the rtS202I changes were combined with the 3TCr substitutions. In summary, infrequent ETV resistance can emerge during prolonged therapy, with selection of additional RT substitutions within a 3TCr HBV background, leading to reduced ETV susceptibility and treatment failure.

Background In patients with chronic hepatitis B (CHB), hepatitis B surface antigen levels (QHBsAg) have recently been associated with predicting response to peg-interferon-alfa, including HBsAg seroconversion (SC) and loss or decline. Long-term nucleos(t)ide analogues (NA) suppresses HBV replication in the majority of patients, however very few actually undergo HBsAg SC. The utility of HBsAg quantitative analysis in these patients is poorly understood, and the impact of multi-drug resistant (MDR) variants has not been explored. Aims To evaluate the QHBsAg decline in a well-characterized cohort of patients with MDR (rtA181T/V) HBV who were treated with >7 years with multiple NA, including at least 3 years of tenofovir (TDF). Methods TDF-109 was an investigator-initiated, prospective, multicentre, open-label study of 60 patients treated with TDF salvage/rescue therapy. All patients had previously failed LAM and subsequent ADVadd- on or switch therapy. The median age was 48.5 years (range 21-80), 77% were males, 67% were HBeAg positive, 67% were of Asian ethnicity and 52% were infected with HBV genotype C. Median follow-up is now 4 years; all patients have achieved an adequate virological response, with 75% (38/51) having undetectable HBV DNA levels. All patients have been maintained on TDF in long-term follow-up, now out to 4 years. QHBsAg titres were retrospectively quantified at baseline and every 6 months and expressed as IU/ml (Roche Elecsys). Results At baseline, median QHBsAg titre was 5226 IU/ml. Baseline QHBsAg titre were positively correlated with HBV DNA levels at baseline, R = 0.33, p = 0.0168). There was a trend for higher baseline QHBsAg levels in HBeAg positive patients (p = 0.1257). The median HBsAg titres were 2772 IU/ml at year 1, 2284 IU/ml at year 2 and 1819 IU/ml at year 3. There was a trend for patients with detectable rtA181T/V variants to have a lower QHBsAg at baseline. There was a trend for patients with no detectable resistance changes or lam

Background: Hepatitis B virus (HBV) infection is influenced by genotype, with genotypes B and C generally associated with higher levels of chronicity and more severe liver disease compared to genotypes A and D. The hepatitis B e antigen (HBeAg) is a powerful suppressor of TIR-mediated innate immune responses. We have previously shown that a cytosolic form of the HBeAg (p22) inhibits IL-1beta-mediated NF-eB activation in hepatocytes, yet the related HBV core protein (p21) had no effect. Since regulation of host innate immune responses is important for establishment of chronic infection, we were interested to determine whether HBeAg-mediated suppression of TIR-mediated immune responses differed for HBV genotypes. Method(s): The p22 gene of HBV genotypes A, B,C and D was cloned into a mammalian expression vector and transfected into PH5CH8 hepatocytes. A plasmid expressing the p21 protein was also transfected. Protein expression was confirmed by western blotting and ELISA. Following stimulation with the TIR ligand IL-1beta, NF-eB promoter activity was measured using luciferase reporter assays. Result(s): The HBV p22 protein down-regulated IL-1beta-mediated NFeB promoter activity in a genotype-specific manner, with highest down-regulation observed for genotypes B and C, compared to genotypes A and D. The related core protein (p21) had no effect on NF-eB promoter activity. Conclusion(s): This is the first study to identify a role for HBV genotype in down-regulation of innate immune responses. Highest suppression was observed for Asian genotypes B and C, providing one possible explanation for the increased chronicity observed in Asia compared to the western world.

Background: In CHB patients, quantitative hepatitis B surface antigen (QHBsAg) have recently been associated with predicting response to peg-interferon-alfa, including HBsAg seroconversion (SC) & loss or decline. Long-term nucleos(t)ide analogues (NA) suppresses HBV replication in the majority of patients, however very few actually undergo HBsAg SC. The utility of QHBsAg analysis in these patients is poorly understood & the impact of multi-drug resistant (MDR) variants has not been explored. Aim(s): To evaluate the QHBsAg decline in a wellcharacterized cohort of patients with MDR (rtA181T/V) HBV who were treated with >7years with multiple NA, including at least 3 years of tenofovir (TDF). Method(s): TDF109 was an investigator-initiated, prospective, multi-centre, open-label study of the efficacy of TDF rescue therapy in 60 patients who had previously failed lamivudine (LAM) & subsequent adefovir (ADV) add-on or switch therapy. We have previously presented virological outcome at 2 years (Patterson, Gut 2011). All patients have been maintained on TDF in long-term follow-up, now out to 4 years. QHBsAg titers were retrospectively quantified at baseline & every 6 months, expressed as IU/ml (Roche Elecsys). Sub-analysis according to baseline viral load & the type of HBV resistance-associated substitutions present at baseline was then performed. Result(s): At baseline, median QHBsAg titer was 5226IU/ml. Baseline QHBsAg positively correlated with HBV DNA levels at baseline, (R = 0.33, p=0.0168). There was a trend for higher baseline QHBsAg levels in HBeAg positive patients (p=0.13). The median HBsAg titers were 2772IU/ml, 2284IU/ml &1819IU/ml at year 1, 2&3 respectively (P<0.0001 for comparison of baseline to year 3). Patients with detectable rtA181T/V variants have a lower QHBsAg at baseline, but more gradual decline in QHBsAg (p=0.002). There was a trend for patients with no detectable resistance changes or LAM resistance HBV Pol at baseline, to have higher baseline QHBsA

The -1G mutant HBV is more prevalent in individuals co-infected with HIV/HBV than in individuals infected with HBV alone and in some cases is the dominant virus in circulation. This mutant is created by the deletion of a dGMP (-1G) from the guanine rich homopolymer sequence located at nts 2,085-2,090 (numbering from EcoRI site as position 1) in the HBV core gene. This deletion causes a frameshift generating a premature stop codon at (64) Asn in the HBV core gene (codon 93 in the precore gene), that truncates the precore protein, precursor of the secreted hepatitis B "e" antigen (HBeAg), and the core protein which forms the viral nucleocapsid. However, the replication phenotype of the -1G mutant HBV is unknown. An in vitro cell culture model in which hepatoma cells were transiently transfected with infectious cDNAs was used to show that the -1G mutant HBV is incapable of autonomous replication and, as expected, replication was restored to wild-type (wt) levels by supplying HBV core protein in trans. Although the -1G mutation had no deleterious effect on intracellular HBV-DNA levels, high levels of -1G mutant HBV relative to wt HBV reduced virus secretion and HBeAg secretion relative to empty vector controls. Importantly, the -1G mutant HBV also caused intracellular retention of truncated precore protein in the endoplasmic reticulum (ER) and Golgi apparatus. Together, these effects may be contributing to the increased pathology observed in the setting of HIV/HBV co-infection.

The development of hepatocellular carcinoma during chronic hepatitis B infection is a multifactorial process thought to be a consequence of several direct and indirect mechanisms. In this review we discuss how viral proteins and cycles of ongoing liver damage and regeneration, coupled with HBV DNA integration and aberrant miRNA expression may enhance the risk for the development of hepatocellular carcinoma. © 2012 Future Medicine Ltd.

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The adoption of carbon capture and storage technology by the minerals industry could permit the direct smelting of ores. The concept is illustrated by describing in outline the processes, technology and pilot-scale testwork needed to treat the lead-zinc ores of McArthur River mine in the Gulf of Carpentaria, Australia, to produce 300 000 t/year zinc and 120 000 t/year lead. It might also be economic to co-produce about 215 000 t/year of steel products at the mine. The benefits of adopting this approach include the elimination of the environmental problems associated with tailings disposal, and a reduction in overall energy requirements due to the elimination of the fine grinding and flotation stages of ore treatment., The adoption of carbon capture and storage technology by the minerals industry could permit the direct smelting of ores. The concept is illustrated by describing in outline the processes, technology and pilot-scale testwork needed to treat the lead-zinc ores of McArthur River mine in the Gulf of Carpentaria, Australia, to produce 300 000 t/year zinc and 120 000 t/year lead. It might also be economic to co-produce about 215 000 t/year of steel products at the mine. The benefits of adopting this approach include the elimination of the environmental problems associated with tailings disposal, and a reduction in overall energy requirements due to the elimination of the fine grinding and flotation stages of ore treatment.

We construct a family of warped AdS_5 compactifications of IIB supergravity that are the holographic duals of the complete set of N=1 fixed points of a Z_2 quiver gauge theory. This family interpolates between the T^{1,1} compactification with no three-form flux and the Z_2 orbifold of the Pilch-Warner geometry which contains three-form flux. This family of solutions is constructed by making the most general Ansatz allowed by the symmetries of the field theory. We use Killing spinor methods because the symmetries impose two simple projection conditions on the Killing spinors, and these greatly reduce the problem. We see that generic interpolating solution has a nontrivial dilaton in the internal five-manifold. We calculate the central charge of the gauge theories from the supergravity backgrounds and find that it is 27/32 of the parent N=2, quiver gauge theory. We believe that the projection conditions that we derived here will be useful for a much larger class of N=1 holographic RG-flows., Comment: 49 pages, 3 figures

We use the framework of matrix factorizations to study topological B-type D-branes on the cubic curve. Specifically, we elucidate how the brane RR charges are encoded in the matrix factors, by analyzing their structure in terms of sections of vector bundles in conjunction with equivariant R-symmetry. One particular advantage of matrix factorizations is that explicit moduli dependence is built in, thus giving us full control over the open-string moduli space. It allows one to study phenomena like discontinuous jumps of the cohomology over the moduli space, as well as formation of bound states at threshold. One interesting aspect is that certain gauge symmetries inherent to the matrix formulation lead to a non-trivial global structure of the moduli space. We also investigate topological tachyon condensation, which enables us to construct, in a systematic fashion, higher-dimensional matrix factorizations out of smaller ones; this amounts to obtaining branes with higher RR charges as composites of ones with minimal charges. As an application, we explicitly construct all rank-two matrix factorizations., Comment: 69p, 6 figs, harvmac; v2: minor changes

We obtain a solution to eleven-dimensional supergravity that consists of M2-branes embedded in a dielectric distribution of M5-branes. Contrary to normal expectations, this solution has maximal supersymmetry for a brane solution (i.e. sixteen supercharges). While the solution is constructed using gauged supergravity in four dimensions, the complete eleven-dimensional solution is given. In particular, we obtain the Killing spinors explicitly, and we find that they are characterised by a duality rotation of the standard Dirichlet projection matrix for M2-branes., Comment: 17 pages; harvmac

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We study the superpotential of a certain class of N=1 supersymmetric type II compactifications with fluxes and D-branes. We show that it has an important two-dimensional meaning in terms of a chiral ring of the topologically twisted theory on the world-sheet. In the open-closed string B-model, this chiral ring is isomorphic to a certain relative cohomology group V, which is the appropriate mathematical concept to deal with both the open and closed string sectors. The family of mixed Hodge structures on V then implies for the superpotential to have a certain geometric structure. This structure represents a holomorphic, N=1 supersymmetric generalization of the well-known N=2 special geometry. It defines an integrable connection on the topological family of open-closed B-models, and a set of special coordinates on the space \cal M of vev's in N=1 chiral multiplets. We show that it can be given a very concrete and simple realization for linear sigma models, which leads to a powerful and systematic method for computing the exact non-perturbative N=1 superpotentials for a broad class of toric D-brane geometries., Comment: 40p, harvmac-b

We outline a general geometric structure that underlies the N=1 superpotentials of a certain class of flux and brane configurations in type II string compactifications on Calabi-Yau threefolds. This ``holomorphic N=1 special geometry'' is in many respects comparable to, and in a sense an extension of, the familiar special geometry in N=2 supersymmetric type II string compactifications. It puts the computation of the instanton-corrected superpotential W of the four-dimensional N=1 string effective action on a very similar footing as the familiar computation of the N=2 prepotential F via mirror symmetry. In this note we present some of the main ideas and results, while more details as well as some explicit computations will appear in a companion paper, Comment: 18 pages, harvmac (b), no figures

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The use of gauged ${\cal N} = 8$ supergravity as a tool in studying the AdS/CFT correspondence for ${\cal N} = 4$ Yang-Mills theory is reviewed. The supergravity potential implies a non-trivial, supersymmetric IR fixed point, and the flow to this fixed point is described in terms of a supergravity kink. The results agree perfectly with earlier, independent field theory results. A supergravity inspired $c$-function, and corresponding $c$-theorem is discussed for general flows, and the simplified form for supersymmetric flows is also given. Flows along the Coulomb branch of the Yang-Mills theory are also described from the five-dimensional perspective., Comment: 12 pages, 3 figures; Latex, ioplppt.sty, iopl12.sty, epsf.sty. Contribution to Strings `99

We obtain first order equations that determine a supersymmetric kink solution in five-dimensional N=8 gauged supergravity. The kink interpolates between an exterior anti-de Sitter region with maximal supersymmetry and an interior anti-de Sitter region with one quarter of the maximal supersymmetry. One eighth of supersymmetry is preserved by the kink as a whole. We interpret it as describing the renormalization group flow in N=4 super-Yang-Mills theory broken to an N=1 theory by the addition of a mass term for one of the three adjoint chiral superfields. A detailed correspondence is obtained between fields of bulk supergravity in the interior anti-de Sitter region and composite operators of the infrared field theory. We also point out that the truncation used to find the reduced symmetry critical point can be extended to obtain a new N=4 gauged supergravity theory holographically dual to a sector of N=2 gauge theories based on quiver diagrams. We consider more general kink geometries and construct a c-function that is positive and monotonic if a weak energy condition holds in the bulk gravity theory. For even-dimensional boundaries, the c-function coincides with the trace anomaly coefficients of the holographically related field theory in limits where conformal invariance is recovered., Comment: 56 pages, three figures, harvmac. v2: improved referencing, corrected discussion of energy conditions. v3: one more reference fixed

States on the Coulomb branch of N=4 super-Yang-Mills theory are studied from the point of view of gauged supergravity in five dimensions. These supersymmetric solutions provide examples of consistent truncation from type IIB supergravity in ten dimensions. A mass gap for states created by local operators and perfect screening for external quarks arise in the supergravity approximation. We offer an interpretation of these surprising features in terms of ensembles of brane distributions., Comment: 19 pages, two figures, latex. v2: reference added, small corrections. v3: corrected unbounded spectrum error

We investigate the prepotential that describes certain F^4 couplings in eight dimensional string compactifications, and show how they can be computed from the solutions of inhomogenous differential equations. These appear to have the form of the Picard-Fuchs equations of a fibration of Sym^2(K3) over P^1. Our findings give support to the conjecture that the relevant geometry which underlies these couplings is given by a five-fold., Comment: 19p, harvmac; One sign in eq. (A.2) changed

We compute, in the large N limit, the quark potential for ${\cal N}=4$ supersymmetric SU(N) Yang-Mills theory broken to $SU(N_1) \times SU(N_2)$. At short distances the quarks see only the unbroken gauge symmetry and have an attractive potential that falls off as 1/L. At longer distances the interquark interaction is sensitive to the symmetry breaking, and other QCD states appear. These states correspond to combinations of the quark-antiquark pair with some number of W-particles. If there is one or more W-particles then this state is unstable because of the coulomb interaction between the W-particles and between the W's and the quarks. As L is decreased the W-particles delocalize and these coulomb branches merge onto a branch with a linear potential. The quarks on this branch see the unbroken gauge group, but the flux tube is unstable to the production of W-particles., Comment: 23 pages, 7 figures, harvmac (b)

We analyze a particular SU(2) invariant sector of the scalar manifold of gauged N=8 supergravity in five dimensions, and find all the critical points of the potential within this sector. The critical points give rise to Anti-de Sitter vacua, and preserve at least an SU(2) gauge symmetry. Consistent truncation implies that these solutions correspond to Anti-de Sitter compactifications of IIB supergravity, and hence to possible near-horizon geometries of 3-branes. Thus we find new conformal phases of softly broken N=4 Yang--Mills theory. One of the critical points preserves N=2 supersymmetry in the bulk and is therefore completely stable, and corresponds to an N=1 superconformal fixed point of the Yang--Mills theory. The corresponding renormalization group flow from the N=4 point has c_{IR}/c_{UV} = 27/32. We also discuss the ten-dimensional geometries corresponding to these critical points., Comment: 14 pages, 1 table, harvmac

We show how certain F^4 couplings in eight dimensions can be computed using the mirror map and K3 data. They perfectly match with the corresponding heterotic one-loop couplings, and therefore this amounts to a successful test of the conjectured duality between the heterotic string on T^2 and F-theory on K3. The underlying quantum geometry appears to be a 5-fold, consisting of a hyperk"ahler 4-fold fibered over a IP^1 base. The natural candidate for this fiber is the symmetric product Sym^2(K3). We are lead to this structure by analyzing the implications of higher powers of E_2 in the relevant Borcherds counting functions, and in particular the appropriate generalizations of the Picard-Fuchs equations for the K3., Comment: 32 p, harvmac; One footnote on page 11 extended; results unchanged; Version subm. to ATMP

We study certain properties of six-dimensional tensionless E-strings (arising from zero size $E_8$ instantons). In particular we show that $n$ E-strings form a bound string which carries an $E_8$ level $n$ current algebra as well as a left-over conformal system with $c=12n-4-{248n \over n+30}$, whose characters can be computed. Moreover we show that the characters of the $n$-string bound state are captured by N=4 U(n) topological Yang-Mills theory on $\half K3$. This relation not only illuminates certain aspects of E-strings but can also be used to shed light on the properties of N=4 topological Yang-Mills theories on manifolds with $b_2^+=1$. In particular the E-string partition functions, which can be computed using local mirror symmetry on a Calabi-Yau three-fold, give the Euler characteristics of the Yang-Mills instanton moduli space on $\half K3$. Moreover, the partition functions are determined by a gap condition combined with a simple recurrence relation which has its origins in a holomorphic anomaly that has been conjectured to exist for N=4 topological Yang-Mills on manifolds with $b_2^+=1$ and is also related to the holomorphic anomaly for higher genus topological strings on Calabi-Yau threefolds., Comment: 49 pages, no figures, harvmac. version 2: Note added, typos removed and formula (6.15) corrected

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We derive modular anomaly equations from the Seiberg-Witten-Donagi curves for softly broken N=4 SU(n) gauge theories. From these equations we can derive recursion relations for the pre-potential in powers of m^2, where m is the mass of the adjoint hypermultiplet. Given the perturbative contribution of the pre-potential and the presence of ``gaps'' we can easily generate the m^2 expansion in terms of polynomials of Eisenstein series, at least for relatively low rank groups. This enables us to determine efficiently the instanton expansion up to fairly high order for these gauge groups, e. g. eighth order for SU(3). We find that after taking a derivative, the instanton expansion of the pre-potential has integer coefficients. We also postulate the form of the modular anomaly equations, the recursion relations and the form of the instanton expansions for the SO(2n) and E_n gauge groups, even though the corresponding Seiberg-Witten-Donagi curves are unknown at this time., Comment: harvmac(b) 28 pages

We consider the BPS states of the $E_8$ non-critical string wound around one of the circles of a toroidal compactification to four dimensions. These states are indexed by their momenta and winding numbers. We find explicit expressions, $G_n$, for the momentum partition functions for the states with winding number $n$. The $G_n$ are given in terms of modular forms. We give a simple algorithm for generating the $G_n$, and we show that they satisfy a recurrence relation that is reminiscent of the holomorphic anomaly equations of Kodaira-Spencer theory., Comment: 17 pages, harvmac(b)

We use the effective action of the $E_n$ non-critical strings to study its BPS spectrum for $0 \le n \le 8$. We show how to introduce mass parameters, or Wilson lines, into the effective action, and then perform the appropriate asymptotic expansions that yield the BPS spectrum. The result is the $E_n$ character expansion of the spectrum, and is equivalent to performing the mirror map on a Calabi-Yau with up to nine K\"ahler moduli. This enables a much more detailed examination of the $E_n$ structure of the theory, and provides extensive checks on the effective action description of the non-critical string. We extract some universal ($E_n$ independent) information concerning the degeneracies of BPS excitations., Comment: 50 pages, harvmac (b)

We study limits of four-dimensional type II Calabi-Yau compactifications with vanishing four-cycle singularities, which are dual to $\IT^2$ compactifications of the six-dimensional non-critical string with $E_8$ symmetry. We define proper subsectors of the full string theory, which can be consistently decoupled. In this way we obtain rigid effective theories that have an intrinsically stringy BPS spectrum. Geometrically the moduli spaces correspond to special geometry of certain non-compact Calabi-Yau spaces of an intriguing form. An equivalent description can be given in terms of Seiberg-Witten curves, given by the elliptic simple singularities together with a peculiar choice of meromorphic differentials. We speculate that the moduli spaces describe non-perturbative non-critical string theories., Comment: 29 pages, harvmac, 1 figure, minor corrections

We show how the Riemann surface $\Sigma$ of $N=2$ Yang-Mills field theory arises in type II string compactifications on Calabi-Yau threefolds. The relevant local geometry is given by fibrations of ALE spaces. The $3$-branes that give rise to BPS multiplets in the string descend to self-dual strings on the Riemann surface, with tension determined by a canonically fixed Seiberg-Witten differential $\lambda$. This gives, effectively, a dual formulation of Yang-Mills theory in which gauge bosons and monopoles are treated on equal footing, and represents the rigid analog of type II-heterotic string duality. The existence of BPS states is essentially reduced to a geodesic problem on the Riemann surface with metric $|\lambda|^2$. This allows us, in particular, to easily determine the spectrum of {\it stable} BPS states in field theory. Moreover, we identify the six-dimensional space $\IR^4\times \Sigma$ as the world-volume of a five-brane and show that BPS states correspond to two-branes ending on this five-brane., Comment: harvmac, 22p, uses epsf, with 3 .eps figures (references added plus other minor corrections)

We show that the genus 34 Seiberg-Witten curve underlying $N=2$ Yang-Mills theory with gauge group $E_6$ yields physically equivalent results to the manifold obtained by fibration of the $E_6$ ALE singularity. This reconciles a puzzle raised by $N=2$ string duality.

Quantum integrable models that possess $N=2$ supersymmetry are investigated on the half-space. Conformal perturbation theory is used to identify some $N=2$ supersymmetric boundary integrable models, and the effective boundary Landau-Ginzburg actions are constructed. It is found that $N=2$ supersymmetry largely determines the boundary action in terms of the bulk, and in particular, the boundary bosonic potential is $|W|^2$, where $W$ is the bulk superpotential. Supersymmetry is also discussed from the perspective of the affine quantum group symmetry of exact scattering matrices, and exact $N=2$ supersymmetry preserving boundary reflection matrices are described., Comment: 11 pages, latex with espcrc2.tex/espcrc2.sty Contribution to the proceedings of the ICTP workshop on Recent Developments in Statistical Mechanics and Quantum Field Theory

The holomorphic prepotential of ultraviolet finite N=2 supersymmetric gauge theories is obtained by a partial twisting of N=1 gauge theory in six dimensions, compactified on $\IR^4\timesT^2$. We show that Ward identities for the conserved chiral $\R$-symmetry in these theories generate a set of constraints on the correlation functions of chiral ring operators. These correlators depend only on the coordinates of the $T^2$, and the constraints are analogs of the Knihnik-Zamolodchikov-Bernard equations at the critical level., Comment: 12 pages, latex