Do Nonresident Fathers Matter? Associations Between Nonresident Fathering and Adolescent Functioning

The present study examined the relationship between nonresident father involvement and adolescent psychosocial functioning among Black and White adolescents. The study sample, drawn from Wave 2 of the National Survey of Families and Households, included 372 adolescents who resided with their biological mother, had a nonresident father, and had no male figure in the household. Analysis indicated that nonresident fathers who had conflictual relationships with resident mothers had more contact with their children. Overall, the quality of the nonresident father-child relationship was a weak predictor of adolescent outcomes, particularly when controlling for the mother-child relationship. However, frequency of father contact was related to poorer adolescent adjustment when quality of the father-child relationship was poor. Conflict in the resident mother-nonresident father relationship was associated with higher levels of adolescent externalizing behavior. Findings of the study suggest that a more holistic conceptualization of nonresident father involvement is needed in order to understand the unique influence of nonresident fathers on adolescent adjustment. Implications of the findings and directions for future research are discussed

Multiple Tunnels in Soil with Shotcrete Linings on Tren Urbano, San Juan, Puerto Rico

Tunnelling was part of the new Tren Urbano transit system in San Juan, Puerto Rico. Four tunnels in soil were designed and constructed with shotcrete linings using the sequential excavation method (SEM), which uses some aspects of the New Austrian Tunneling Method (NATM). Four 6-m-diameter tunnels of about 100 m in length were required to preserve two historic structures located above the subway alignment. Two of the four tunnels were constructed as part of a turnout to a future line. Cover over the SEM tunnels ranges from 20 to 5 m. Some of the tunnels are located less than 1 m from each other in the turnout section. Detailed analysis of the staged construction was undertaken to design shotcrete lining thickness, shotcrete strength, and reinforcing with welded wire fabric and lattice girders. Several variations in lining section were required, which depended on sequence of tunnel excavation and depth of cover. Further refinement of the lining design was possible by considering the initial lining as permanent since it had been constructed with final structure quality requirements. Compensation grouting effectively mitigated ground movements and building settlement was limited. Tunnel lining convergence measurements revealed the lining displacements due to excavation of adjacent or overlying tunnel construction to be within acceptable limits. Design and construction of the tunnels as sequentially excavated with shotcrete support (SEM) was unprecedented in Puerto Rico and not in widespread practice in the continental United States. Further, this was the first major United States underground transit construction project with design-build project delivery

Open-channel structure of a pentameric ligand-gated ion channel reveals a mechanism of leaflet-specific phospholipid modulation

Pentameric ligand-gated ion channels (pLGICs) mediate synaptic transmission and are sensitive to their lipid environment. The mechanism of phospholipid modulation of any pLGIC is not well understood. We demonstrate that the model pLGIC, ELIC (Erwinia ligand-gated ion channel), is positively modulated by the anionic phospholipid, phosphatidylglycerol, from the outer leaflet of the membrane. To explore the mechanism of phosphatidylglycerol modulation, we determine a structure of ELIC in an open-channel conformation. The structure shows a bound phospholipid in an outer leaflet site, and structural changes in the phospholipid binding site unique to the open-channel. In combination with streamlined alchemical free energy perturbation calculations and functional measurements in asymmetric liposomes, the data support a mechanism by which an anionic phospholipid stabilizes the activated, open-channel state of a pLGIC by specific, state-dependent binding to this site

Bapineuzumab for mild to moderate Alzheimer’s disease in two global, randomized, phase 3 trials

Background Our objective was to evaluate the efficacy (clinical and biomarker) and safety of intravenous bapineuzumab in patients with mild to moderate Alzheimer’s disease (AD). Methods Two of four phase 3, multicenter, randomized, double-blind, placebo-controlled, 18-month trials were conducted globally: one in apolipoprotein E ε4 carriers and another in noncarriers. Patients received bapineuzumab 0.5 mg/kg (both trials) or 1.0 mg/kg (noncarrier trial) or placebo every 13 weeks. Coprimary endpoints were change from baseline to week 78 on the 11-item Alzheimer’s Disease Assessment Scale–Cognitive subscale and the Disability Assessment for Dementia. Results A total of 683 and 329 patients completed the current carrier and noncarrier trials, respectively, which were terminated prematurely owing to lack of efficacy in the two other phase 3 trials of bapineuzumab in AD. The current trials showed no significant difference between bapineuzumab and placebo for the coprimary endpoints and no effect of bapineuzumab on amyloid load or cerebrospinal fluid phosphorylated tau. (Both measures were stable over time in the placebo group.) Amyloid-related imaging abnormalities with edema or effusion were confirmed as the most notable adverse event. Conclusions These phase 3 global trials confirmed lack of efficacy of bapineuzumab at tested doses on clinical endpoints in patients with mild to moderate AD. Some differences in the biomarker results were seen compared with the other phase 3 bapineuzumab trials. No unexpected adverse events were observed. Trial registration Noncarriers (3000) ClinicalTrials.gov identifier NCT00667810; registered 24 Apr 2008. Carriers (3001) ClinicalTrials.gov identifier NCT00676143; registered 2 May 2008

Application of programmable bio-nano-chip system for the quantitative detection of drugs of abuse in oral fluids

Objective: There is currently a gap in on-site drug of abuse monitoring. Current detection methods involve invasive sampling of blood and urine specimens, or collection of oral fluid, followed by qualitative screening tests using immunochromatographic cartridges. While remote laboratories then may provide confirmation and quantitative assessment of a presumptive positive, this instrumentation is expensive and decoupled from the initial sampling making the current drug-screening program inefficient and costly. The authors applied a noninvasive oral fluid sampling approach integrated with the in-development chip-based Programmable bio-nano-chip (p-BNC) platform for the detection of drugs of abuse. Method: The p-BNC assay methodology was applied for the detection of tetrahydrocannabinol, morphine, amphetamine, methamphetamine, cocaine, methadone and benzodiazepines, initially using spiked buffered samples and, ultimately, using oral fluid specimen collected from consented volunteers. Results: Rapid (∼10 min), sensitive detection (∼ng/mL) and quantitation of 12 drugs of abuse was demonstrated on the p-BNC platform. Furthermore, the system provided visibility to time-course of select drug and metabolite profiles in oral fluids; for the drug cocaine, three regions of slope were observed that, when combined with concentration measurements from this and prior impairment studies, information about cocaine-induced impairment may be revealed. Conclusions: This chip-based p-BNC detection modality has significant potential to be used in the future by law enforcement officers for roadside drug testing and to serve a variety of other settings, including outpatient and inpatient drug rehabilitation centers, emergency rooms, prisons, schools, and in the workplace

Inhibition of SLPI ameliorates disease activity in experimental autoimmune encephalomyelitis

<p>Abstract</p> <p>Background</p> <p>The secretory leukocyte protease inhibitor (SLPI) exerts wide ranging effects on inflammatory pathways and is upregulated in EAE but the biological role of SLPI in EAE, an animal model of multiple sclerosis is unknown</p> <p>Methods</p> <p>To investigate the pathophysiological effects of SLPI within EAE, we induced SLPI-neutralizing antibodies in mice and rats to determine the clinical severity of the disease. In addition we studied the effects of SLPI on the anti-inflammatory cytokine TGF-β.</p> <p>Results</p> <p>The induction of SLPI neutralizing antibodies resulted in a milder disease course in mouse and rat EAE. SLPI neutralization was associated with increased serum levels of TGF-β and increased numbers of FoxP3+ CD4+ T cells in lymph nodes. <it>In vitro</it>, the addition of SLPI significantly decreased the number of functional FoxP3+ CD25^hiCD4+ regulatory T cells in cultures of naive human CD4+ T cells. Adding recombinant TGF-β to SLPI-treated human T cell cultures neutralized SLPI's inhibitory effect on regulatory T cell differentiation.</p> <p>Conclusion</p> <p>In EAE, SLPI exerts potent pro-inflammatory actions by modulation of T-cell activity and its neutralization may be beneficial for the disease.</p

Complement Factor H-Related Proteins CFHR2 and CFHR5 Represent Novel Ligands for the Infection-Associated CRASP Proteins of Borrelia burgdorferi

Background: One virulence property of Borrelia burgdorferi is its resistance to innate immunity, in particular to complement-mediated killing. Serum-resistant B. burgdorferi express up to five distinct complement regulator-acquiring surface proteins (CRASP) which interact with complement regulator factor H (CFH) and factor H-like protein 1 (FHL1) or factor H-related protein 1 (CFHR1). In the present study we elucidate the role of the infection-associated CRASP-3 and CRASP-5 protein to serve as ligands for additional complement regulatory proteins as well as for complement resistance of B. burgdorferi. Methodology/Principal Findings: To elucidate whether CRASP-5 and CRASP-3 interact with various human proteins, both borrelial proteins were immobilized on magnetic beads. Following incubation with human serum, bound proteins were eluted and separated by Glycine-SDS-PAGE. In addition to CFH and CFHR1, complement regulators CFHR2 and CFHR5 were identified as novel ligands for both borrelial proteins by employing MALDI-TOF. To further assess the contributions of CRASP-3 and CRASP-5 to complement resistance, a serum-sensitive B. garinii strain G1 which lacks all CFH-binding proteins was used as a valuable model for functional analyses. Both CRASPs expressed on the B. garinii outer surface bound CFH as well as CFHR1 and CFHR2 in ELISA. In contrast, live B. garinii bound CFHR1, CFHR2, and CFHR5 and only miniscute amounts of CFH as demonstrated by serum adsorption assays and FACS analyses. Further functional analysis revealed that upon NHS incubation, CRASP-3 or CRASP-5 expressing borreliae were killed by complement. Conclusions/Significance: In the absence of CFH and the presence of CFHR1, CFHR2 and CFHR5, assembly and integration of the membrane attack complex was not efficiently inhibited indicating that CFH in co-operation with CFHR1, CFHR2 and CFHR5 supports complement evasion of B. burgdorferi

On the Progenitor of Binary Neutron Star Merger GW170817

On 2017 August 17 the merger of two compact objects with masses consistent with two neutron stars was discovered through gravitational-wave (GW170817), gamma-ray (GRB 170817A), and optical (SSS17a/AT 2017gfo) observations. The optical source was associated with the early-type galaxy NGC 4993 at a distance of just ~40 Mpc, consistent with the gravitational-wave measurement, and the merger was localized to be at a projected distance of ~2 kpc away from the galaxy's center. We use this minimal set of facts and the mass posteriors of the two neutron stars to derive the first constraints on the progenitor of GW170817 at the time of the second supernova (SN). We generate simulated progenitor populations and follow the three-dimensional kinematic evolution from binary neutron star (BNS) birth to the merger time, accounting for pre-SN galactic motion, for considerably different input distributions of the progenitor mass, pre-SN semimajor axis, and SN-kick velocity. Though not considerably tight, we find these constraints to be comparable to those for Galactic BNS progenitors. The derived constraints are very strongly influenced by the requirement of keeping the binary bound after the second SN and having the merger occur relatively close to the center of the galaxy. These constraints are insensitive to the galaxy's star formation history, provided the stellar populations are older than 1 Gyr.The authors gratefully acknowledge the support of the United States National Science Foundation (NSF) for the construction and operation of the LIGO Laboratory and Advanced LIGO as well as the Science and Technology Facilities Council (STFC) of the United Kingdom, the MaxPlanck-Society (MPS), and the State of Niedersachsen/ Germany for support of the construction of Advanced LIGO and construction and operation of the GEO600 detector. Additional support for Advanced LIGO was provided by the Australian Research Counci

Gravitational Waves and Gamma-Rays from a Binary Neutron Star Merger: GW170817 and GRB 170817A

On 2017 August 17, the gravitational-wave event GW170817 was observed by the Advanced LIGO and Virgo detectors, and the gamma-ray burst (GRB) GRB 170817A was observed independently by the Fermi Gamma-ray Burst Monitor, and the Anti-Coincidence Shield for the Spectrometer for the International Gamma-Ray Astrophysics Laboratory. The probability of the near-simultaneous temporal and spatial observation of GRB 170817A and GW170817 occurring by chance is $5.0\times {10}^{-8}$. We therefore confirm binary neutron star mergers as a progenitor of short GRBs. The association of GW170817 and GRB 170817A provides new insight into fundamental physics and the origin of short GRBs. We use the observed time delay of $(+1.74\pm 0.05)\,{\rm{s}}$ between GRB 170817A and GW170817 to: (i) constrain the difference between the speed of gravity and the speed of light to be between $-3\times {10}^{-15}$ and $+7\times {10}^{-16}$ times the speed of light, (ii) place new bounds on the violation of Lorentz invariance, (iii) present a new test of the equivalence principle by constraining the Shapiro delay between gravitational and electromagnetic radiation. We also use the time delay to constrain the size and bulk Lorentz factor of the region emitting the gamma-rays. GRB 170817A is the closest short GRB with a known distance, but is between 2 and 6 orders of magnitude less energetic than other bursts with measured redshift. A new generation of gamma-ray detectors, and subthreshold searches in existing detectors, will be essential to detect similar short bursts at greater distances. Finally, we predict a joint detection rate for the Fermi Gamma-ray Burst Monitor and the Advanced LIGO and Virgo detectors of 0.1–1.4 per year during the 2018–2019 observing run and 0.3–1.7 per year at design sensitivity.The authors gratefully acknowledge the support of the United States National Science Foundation (NSF) for the construction and operation of the LIGO Laboratory and Advanced LIGO as well as the Science and Technology Facilities Council (STFC) of the United Kingdom, the Max-PlanckSociety (MPS), and the State of Niedersachsen/Germany for support of the construction of Advanced LIGO and construction and operation of the GEO600 detector. Additional support for Advanced LIGO was provided by the Australian Research Council. The authors gratefully acknowledge the Italian Istituto Nazionale di Fisica Nucleare (INFN), the French Centre National de la Recherche Scientifique (CNRS) and the Foundation for Fundamental Research on Matter supported by the Netherlands Organisation for Scientific Research, for the construction and operation of the Virgo detector and the creation and support of the EGO consortium. The authors also gratefully acknowledge research support from these agencies as well as by the Council of Scientific and Industrial Research of India, the Department of Science and Technology, India, the Science & Engineering Research Board (SERB), India, the Ministry of Human Resource Development, India, the Spanish Agencia Estatal de Investigación, the Vicepresidència i Conselleria d’Innovació Recerca i Turisme and the Conselleria d’Educació i Universitat del Govern de les Illes Balears, the Conselleria d’Educació Investigació Cultura i Esport de la Generalitat Valenciana, the National Science Centre of Poland, the Swiss National Science Foundation (SNSF), the Russian Foundation for Basic Research, the Russian Science Foundation, the European Commission, the European Regional Development Funds (ERDF), the Royal Society, the Scottish Funding Council, the Scottish Universities Physics Alliance, the Hungarian Scientific Research Fund (OTKA), the Lyon Institute of Origins (LIO), the National Research, Development and Innovation Office Hungary (NKFI), the National Research Foundation of Korea, Industry Canada and the Province of Ontario through the Ministry of Economic Development and Innovation, the Natural Science and Engineering Research Council Canada, the Canadian Institute for Advanced Research, the Brazilian Ministry of Science, Technology, Innovations, and Communications, the International Center for Theoretical Physics South American Institute for Fundamental Research (ICTP-SAIFR), the Research Grants Council of Hong Kong, the National Natural Science Foundation of China (NSFC), the Leverhulme Trust, the Research Corporation, the Ministry of Science and Technology (MOST), Taiwan and the Kavli Foundation. The authors gratefully acknowledge the support of the NSF, STFC, MPS, INFN, CNRS and the State of Niedersachsen/Germany for provision of computational resources. The USRA co-authors gratefully acknowledge NASA funding through contract NNM13AA43C. The UAH coauthors gratefully acknowledge NASA funding from cooperative agreement NNM11AA01A. E.B. and T.D.C. are supported by an appointment to the NASA Postdoctoral Program at the Goddard Space Flight Center, administered by Universities Space Research Association under contract with NASA. D.K., C.A.W.H., C.M.H., and T.L. gratefully acknowledge NASA funding through the Fermi GBM project. Support for the German contribution to GBM was provided by the Bundesministerium für Bildung und Forschung (BMBF) via the Deutsches Zentrum für Luft und Raumfahrt (DLR) under contract number 50 QV 0301. A.v.K. was supported by the Bundesministeriums fr Wirtschaft und Technologie (BMWi) through DLR grant 50 OG 1101. N.C. and J.B. acknowledge support from NSF under grant PHY-1505373. S.M.B. acknowledges support from Science Foundation Ireland under grant 12/IP/1288. This work is based on observations with INTEGRAL, an ESA project with instruments and science data center funded by ESA member states (especially the PI countries: Denmark, France, Germany, Italy, Switzerland, Spain), and with the participation of Russia and the USA. The INTEGRAL SPI project has been completed under the responsibility and leadership of CNES. The SPI-ACS detector system has been provided by MPE Garching/Germany. The SPI team is grateful to ASI, CEA, CNES, DLR, ESA, INTA, NASA and OSTC for their support. The Italian INTEGRAL team acknowledges the support of ASI/INAF agreement n. 2013- 025-R.1. R.D. and A.v.K. acknowledge the German INTEGRAL support through DLR grant 50 OG 1101. A.L. and R.S. acknowledge the support from the Russian Science Foundation (grant 14-22-00271). A.D. is funded by Spanish MINECO/ FEDER grant ESP2015-65712-C5-1-R. Some of the results in this paper have been derived using the HEALPix (Gorski et al. 2005) package. We are grateful VirtualData from LABEX P2IO for enabling access to the StratusLab academic cloud. We acknowledge the continuous support by the INTEGRAL Users Group and the exceptionally efficient support by the teams at ESAC and ESOC for the scheduling of the targeted follow-up observations

Estimating the Contribution of Dynamical Ejecta in the Kilonova Associated with GW170817

The source of the gravitational-wave (GW) signal GW170817, very likely a binary neutron star merger, was also observed electromagnetically, providing the first multi-messenger observations of this type. The two-week-long electromagnetic (EM) counterpart had a signature indicative of an r-process-induced optical transient known as a kilonova. This Letter examines how the mass of the dynamical ejecta can be estimated without a direct electromagnetic observation of the kilonova, using GW measurements and a phenomenological model calibrated to numerical simulations of mergers with dynamical ejecta. Specifically, we apply the model to the binary masses inferred from the GW measurements, and use the resulting mass of the dynamical ejecta to estimate its contribution (without the effects of wind ejecta) to the corresponding kilonova light curves from various models. The distributions of dynamical ejecta mass range between M-ej = 10(-3) - 10(-2) M-circle dot for various equations of state, assuming that the neutron stars are rotating slowly. In addition, we use our estimates of the dynamical ejecta mass and the neutron star merger rates inferred from GW170817 to constrain the contribution of events like this to the r-process element abundance in the Galaxy when ejecta mass from post-merger winds is neglected. We find that if greater than or similar to 10% of the matter dynamically ejected from binary neutron star (BNS) mergers is converted to r-process elements, GW170817-like BNS mergers could fully account for the amount of r-process material observed in the Milky Way.The authors gratefully acknowledge the support of the United States National Science Foundation (NSF) for the construction and operation of the LIGO Laboratory and Advanced LIGO as well as the Science and Technology Facilities Council (STFC) of the United Kingdom, the MaxPlanck-Society (MPS), and the State of Niedersachsen/ Germany for support of the construction of Advanced LIGO and construction and operation of the GEO600 detector. Additional support for Advanced LIGO was provided by the Australian Research Council. The authors gratefully acknowledge the Italian Istituto Nazionale di Fisica Nucleare (INFN), the French Centre National de la Recherche Scientifique (CNRS) and the Foundation for Fundamental Research on Matter supported by the Netherlands Organisation for Scientific Research, for the construction and operation of the Virgo detector and the creation and support of the EGO consortium. The authors also gratefully acknowledge research support from these agencies as well as by the Council of Scientific and Industrial Research of India, the Department of Science and Technology, India, the Science & Engineering Research Board (SERB), India, the Ministry of Human Resource Development, India, the Spanish Agencia Estatal de Investigación, the Vicepresidència i Conselleria d’Innovació Recerca i Turisme and the Conselleria d’Educació i Universitat del Govern de les Illes Balears, the Conselleria d’Educació Investigació Cultura i Esport de la Generalitat Valenciana, the National Science Centre of Poland, the Swiss National Science Foundation (SNSF), the Russian Foundation for Basic Research, the Russian Science Foundation, the European Commission, the European Regional Development Funds (ERDF), the Royal Society, the Scottish Funding Council, the Scottish Universities Physics Alliance, the Hungarian Scientific Research Fund (OTKA), the Lyon Institute of Origins (LIO), the National Research, Development and Innovation Office Hungary (NKFI), the National Research Foundation of Korea, Industry Canada and the Province of Ontario through the Ministry of Economic Development and Innovation, the Natural Science and Engineering Research Council Canada, the Canadian Institute for Advanced Research, the Brazilian Ministry of Science, Technology, Innovations, and Communications, the International Center for Theoretical Physics South American Institute for Fundamental Research (ICTP-SAIFR), the Research Grants Council of Hong Kong, the National Natural Science Foundation of China (NSFC), the Leverhulme Trust, the Research Corporation, the Ministry of Science and Technology (MOST), Taiwan and the Kavli Foundation. The authors gratefully acknowledge the support of the NSF, STFC, MPS, INFN, CNRS, and the State of Niedersachsen/Germany for provision of computational resources