A Multiantigenic DNA Vaccine That Induces Broad Hepatitis C Virus-Specific T-Cell Responses in Mice

There are 3 to 4 million new hepatitis C virus (HCV) infections annually around the world, but no vaccine is available. Robust T-cell mediated responses are necessary for effective clearance of the virus, and DNA vaccines result in a cell-mediated bias. Adjuvants are often required for effective vaccination, but during natural lytic viral infections damage-associated molecular patterns (DAMPs) are released, which act as natural adjuvants. Hence, a vaccine that induces cell necrosis and releases DAMPs will result in cell-mediated immunity (CMI), similar to that resulting from natural lytic viral infection. We have generated a DNA vaccine with the ability to elicit strong CMI against the HCV nonstructural (NS) proteins (3, 4A, 4B, and 5B) by encoding a cytolytic protein, perforin (PRF), and the antigens on a single plasmid. We examined the efficacy of the vaccines in C57BL/6 mice, as determined by gamma interferon enzyme-linked immunosorbent spot assay, cell proliferation studies, and intracellular cytokine production. Initially, we showed that encoding the NS4A protein in a vaccine which encoded only NS3 reduced the immunogenicity of NS3, whereas including PRF increased NS3 immunogenicity. In contrast, the inclusion of NS4A increased the immunogenicity of the NS3, NS4B, andNS5B proteins, when encoded in a DNA vaccine that also encoded PRF. Finally, vaccines that also encoded PRF elicited similar levels of CMI against each protein after vaccination with DNA encoding NS3, NS4A, NS4B, and NS5B compared to mice vaccinated with DNA encoding only NS3 or NS4B/5B. Thus, we have developed a promising ``multiantigen'' vaccine that elicits robust CMI. IMPORTANCE Since their development, vaccines have reduced the global burden of disease. One strategy for vaccine development is to use commercially viable DNA technology, which has the potential to generate robust immune responses. Hepatitis C virus causes chronic liver infection and is a leading cause of liver cancer. To date, no vaccine is currently available, and treatment is costly and often results in side effects, limiting the number of patients who are treated. Despite recent advances in treatment, prevention remains the key to efficient control and elimination of this virus. Here, we describe a novel DNA vaccine against hepatitis C virus that is capable of inducing robust cell-mediated immune responses in mice and is a promising vaccine candidate for humans.

Inventario agroecológico de las especies de Gallina ciega (Phyllophaga spp) en la Región I de Nicaragua y validación de trampas artesanales de luz para el control de adultos en dos localidades del municipio de Estelí, Nicaragua

De mayo a octubre de 1996 se hizo un inventario agroecológico de las especies de gallina ciega (Phyllophaga spp.) en la región T de Nicaragua con el objetivo de determinar la relación entre la diversidad de especies de gallina ciega con precipitación, tamaño y años de uso de la parcela y historial de daño(%) y validación de trampas luz artesanal para control de adultos de gallina ciega en Miraflor y Almaciguera, con el fin de confirmar su efectividad. Se muestrearon 61 localidades en 18 municipios, agrupados por rangos de precipitación en cuatro estratos. La unidad muestra! fué el número de insectos adultos de gallina ciega recolectados por los mismos agricultores en cada finca. Para la identificación se utilizaron las claves desarrolladas por King (1984); Morón (198S); Woodruffy Beck (1989) y Coto (1990). Se realizó un diagoóstico sobre conocimiento de la plaga y el manejo al cultivo por medio de encuestas. Se hizo análisis de correlación simple. La mayor parte de la encuesta fue analizada en términos de porcentajes. Se utilizó la metodología de captura y recaptura de insectos marcados con esmalte para uñas y escarchas de colores diferentes. Los insectos fueron hllerados desde S hasta 21m de distancia de la trampa marcándose grupos de cinco hasta SO insectos. Se consideró un factor correctivo de comparación entre distancias y analisis de frecuencia de recaptura con observaciones cada 15 minutos. Se realizó muestreo de larvas posterior a los ensayos de liberación. La población de gallina ciega en la región T es diviersa. Se reportan 17 especies de los cuales sólo 9 se identificaron: Phyllophaga (Chlaenobia) aequata (Bates), 1888; P. (Phytalus) cometes Bates, 1888; P. (Rorulenta) elenon.' Saylor, 1938; P. (P) lenis Horn, 1887; P.(P) menetriesi Blanchard, 1850; P. (P) obsoleta (Biancbard), 1850; P. (Chlaenobia) tumulosa (Bates), 1888; P. (Rorulenta) vicina Moser, 1918 y P. yucateca (Bates), 1889. Las especies no identificadas fueron distinguidas por números. Las especies 1, 3, 4, 5, 6, 7, 8 y 9 no se identificaron. P. Lenis, P. yucateca, P, vicina, P.elenon.f, P. menetriesi y P. obsoleta son las especies que, en este orden, sobresalen numéricamente. Las cantidades de especímenes por especies de gallina ciega no presentan relación con rangos de precipitación, historial de daño (%), tamaño y años de uso de la aparcela, ni entre ellas mismas. El 60"/o de los agricultores no conoce al adulto de gallina ciega y el 80% no logra diferenciar claramente los sintomas en una planta dañada. No se registraron recapturas de insectos adultos de gallina ciega en las trampas. El análisis cuantitativo no se realizó. La mayor parte de los insectos liberados establecieron vuelo. Muestreos de larvas de gallina ciega indican que sólo en Miraflor habían cantidades de adultos justificables a los ensayos. El promedio de plantas dañadas por gallina ciega según los agricultores es de 15%. Se recomienda impulsar estudios básicos sobre la diversidad de especies de gallina ciega en el país y difundir el conocimiento sobre la biología y manejo de gallina ciega entre los pequeños agricultores. Futuros ensayos con trampas luz deben considerar el aumento de la calidad y la consistencia de la fuente luminosa y establecerlas cerca de las plantas hospederas de adultos.

Biblical evidence from Obadiah and Psalm 137 for an Edomite treaty betrayal of Judah in the sixth century B.C.E.

Abstract: Focusing on Obadiah and Psalm 137, this article provides biblical evidence for an Edomite treaty betrayal of Judah during the Babylonian crisis ca. 588–586 B.C.E. After setting a context that includes the use of treaties in the ancient Near East to establish expectations for political relationships and the likelihood that Edom could operate as a political entity in the Judahite Negev during the Babylonian assault, this article demonstrates that Obadiah’s poetics include a density of inverted form and content (a reversal motif) pointing to treaty betrayal. Obadiah’s modifications of Jeremiah 49, a text with close thematic and terminological parallels, evidence an Edomite treaty betrayal of Judah. Moreover, the study shows that Obadiah is replete with treaty allusions. A study of Psalm 137 in comparison with Aramaic treaty texts from Sefire reveals that this difficult psalm also evidences a treaty betrayal by Edom and includes elements appropriate for treaty curses. The article closes with a discussion of piecemeal data from a few other biblical texts, a criticism of the view that Edom was innocent during the Babylonian crisis, and a suggestion that this treaty betrayal may have contributed to the production of some anti-Edom biblical material.

Efecto de diferentes densidades de siembra sobre el crecimiento y rendimiento del cultivo de chía (Salvia hispánica L.) Sébaco, Matagalpa, 2015

Este trabajo se realizó con la finalidad de d eterminar la influencia de diferentes densidades de siembra (10, 20, 30 y 40 plantas/m) , sobre el crecimiento, desarrollo y rendimiento de l cultivo de chía ( Salvia hispánica L.) ; se efectuó análisis económico a través de cálculo de costos de producción para determinar la rentabilidad de los tratamientos . Se estableció en el periodo de septiembre 2014 a febrero 2015, en la finca Tamarindo de Oro, de la ciudad de Sébaco, Matagalpa, ubicado a 1 02 km al N orte de Managua. Se utilizó un diseño experimental uní - factorial en arreglos de b loques completos al azar, con 4 tratamientos y 6 repeticiones. Las variables evaluadas fueron, altura de planta, diámetro de tallo, número de ramas primarias y secundarias, número de espigas y r endimiento a la cosecha, presentando en todas ellas diferencia estadística significativa , a excepción de la variable de rendimiento . Para la variable altura de planta, en la densidad más alta (40 plantas/m) , se obtuvo la m ayor altura con un promedio de 1.24 metros. La densidad más baja (10 plantas/m), fue la que logró los mejores resultado en las variables diámetro ( 0.83 mm ) , ramas primarias ( 12 unidad ) , secundarias (15 unidad ) , espigas ( 27 unidad ) y rendimiento (826.46 kg/ha) . El análisis económico demuestra una relación beneficio costos mayor de 1 esto quiere decir que todos los tratamiento s presenta ron una rentabilidad viable, donde el tratamiento a 1 de 10 plantas/m, es mayor en relación a los demás

Rubens Paiva

Apresenta ensaio biográfico, discursos, cronologia, fotografias e documentos sobre a trajetória pessoal e política de Rubens Paiva.

Initial Hydraulic modelling and Levee Stability Analysis of the Triple M Ranch Restoration Project

“Advanced Watershed Science and Policy (ESSP 660)” is a graduate class taught in the Master of Science in Coastal and Watershed Science & Policy program at California State University Monterey Bay (CSUMB). In 2007, the class was taught in four 4-week modules, each focusing on a local watershed issue. This report is one outcome of one of those 4-week modules taught in the fall 2007 session. (Document contains 32 pages)

Carmel Lagoon Water Quality and Steelhead Soundings: Fall 2007

ESSP 660 Advanced Watershed Science and Policy is a graduate class taught in the Master of Science in Coastal and Watershed Science & Policy program at California State University Monterey Bay. In 2007, the class was taught in four 4-week modules, each focusing on making a small contribution to a local watershed issue. This report describes the results of one of those 4-week modules – on Carmel Lagoon Water Quality and Ecology. The module was lead instructed by Fred Watson (CSUMB) and Kevan Urquhart (MPWMD). (Document contains 54 pages)

Control of Variable Watermilfoil in Bashan Lake, CT with 2,4-D: Monitoring of Lake and Well Water.

Variable watermilfoil (Myriophyllum heterophyllum Michx.) has recently become a problem in Bashan Lake, East Haddam, CT, USA. By 1998, approximately 4 ha of the 110 ha lake was covered with variable watermilfoil. In 1999, the milfoil was spot treated with Aquacide®, an 18% active ingredient of the sodium salt of 2,4-D [(2,4-dichlorophenoxy) acetic acid], applied at a rate of 114 kg/ha. Aquacide® was used because labeling regarding domestic water intakes and irrigation limitations prevented the use of Navigate® or AquaKleen®, a 19% active ingredient of the butoxyethyl ester of 2,4-D. Variable watermilfoil was partially controlled in shallow protected coves but little control occurred in deeper more exposed locations. 2,4-D levels in the treatment sites were lower than desired and offsite dilution was rapid. In 2000, the United States Environmental Protection Agency (USEPA) issued a special local need (SLN) registration to allow the use of Navigate ® or AquaKleen® in lakes with potable and irrigation water intakes. Navigate® was applied at a rate of 227 kg/ha to the same areas as treated in 1999. An additional 2 ha of variable watermilfoil was treated with Navigate® in 2001, and 0.4 ha was treated in mid-September. Dilution of the 2,4-D ester formulation to untreated areas was slower than with the salt formulation. Concentrations of 2,4-D exceeded 1000 μg/ L in several lake water samples in 2000 but not 2001. Nearly all of the treated variable watermilfoil was controlled in both years. The mid-September treatment appeared as effective as the spring and early summer treatments. Testing of homeowner wells in all 3 years found no detectable levels of 2,4-D.(PDF contains 8 pages.)

Eurasian watermilfoil biomass associated with insect herbivores in New York

A study of aquatic plant biomass within Cayuga Lake, New York spans twelve years from 1987-1998. The exotic Eurasian watermilfoil ( Myriophyllum spicatum L.) decreased in the northwest end of the lake from 55% of the total biomass in 1987 to 0.4% in 1998 and within the southwest end from 50% in 1987 to 11% in 1998. Concurrent with the watermilfoil decline was the resurgence of native species of submersed macrophytes. During this time we recorded for the first time in Cayuga Lake two herbivorous insect species: the aquatic moth Acentria ephemerella , first observed in 1991, and the aquatic weevil Euhrychiopsis lecontei , first found in 1996 . Densities of Acentria in southwest Cayuga Lake averaged 1.04 individuals per apical meristem of Eurasian watermilfoil for the three-year period 1996-1998. These same meristems had Euhrychiopsis densities on average of only 0.02 individuals per apical meristem over the same three-year period. A comparison of herbivore densities and lake sizes from five lakes in 1997 shows that Acentria densities correlate positively with lake surface area and mean depth, while Euhrychiopsis densities correlate negatively with lake surface area and mean depth. In these five lakes, Acentria densities correlate negatively with percent composition and dry mass of watermilfoil. However, Euhrychiopsis densities correlate positively with percent composition and dry mass of watermilfoil. Finally, Acentria densities correlate negatively with Euhrychiopsis densities suggesting interspecific competition.

Herald Higher Education Awards

Jisc is sponsoring the innovation technology excellence category in the inaugural Herald Higher Education Awards, the first awards to recognise best practice specifically in Scottish higher education. Jason Miles-Campbell, head of Jisc Scotland and Jisc Northern Ireland, tells us about the awards and how to enter.

An Algebraic Preservation Theorem for Aleph-Zero Categorical Quantified Constraint Satisfaction

23 p. -- An extended abstract of this work appears in the proceedings of the 2012 ACM/IEEE Symposium on Logic in Computer Science

Comparison of resident and tourist preferences for public beach access

As coastal destinations continue to grow, due to tourism and residential expansion, the demand for public beach access and related amenities will also increase. As a resultagencies that provide beach access and related amenities face challenges when considering both residents and visitors use beaches and likely possess different needs, as well as different preferences for management decisions. Being a resident of a coastal county provides more opportunity to use local beaches, but coastal tourism is an important and growing economic engine in coastal communities (Kriesel, Landry, & Keeler, 2005; Pogue & Lee, 1999). Therefore, providing agencies with a comprehensive assessment of the differences between these two groups will increase the likelihood of effective management programs and policies for the provision of public beach access and related amenities. The purpose of this paper was to use a stated preference choice method (SPCM) to identify the extent of both residents’ and visitors’ preferences for public beach management options. (PDF contains 4 pages)

Planar reflection of gaseous detonations

Pipes containing flammable gaseous mixtures may be subjected to internal detonation. When the detonation normally impinges on a closed end, a reflected shock wave is created to bring the flow back to rest. This study built on the work of Karnesky (2010) and examined deformation of thin-walled stainless steel tubes subjected to internal reflected gaseous detonations. A ripple pattern was observed in the tube wall for certain fill pressures, and a criterion was developed that predicted when the ripple pattern would form. A two-dimensional finite element analysis was performed using Johnson-Cook material properties; the pressure loading created by reflected gaseous detonations was accounted for with a previously developed pressure model. The residual plastic strain between experiments and computations was in good agreement.

During the examination of detonation-driven deformation, discrepancies were discovered in our understanding of reflected gaseous detonation behavior. Previous models did not accurately describe the nature of the reflected shock wave, which motivated further experiments in a detonation tube with optical access. Pressure sensors and schlieren images were used to examine reflected shock behavior, and it was determined that the discrepancies were related to the reaction zone thickness extant behind the detonation front. During these experiments reflected shock bifurcation did not appear to occur, but the unfocused visualization system made certainty impossible. This prompted construction of a focused schlieren system that investigated possible shock wave-boundary layer interaction, and heat-flux gauges analyzed the boundary layer behind the detonation front. Using these data with an analytical boundary layer solution, it was determined that the strong thermal boundary layer present behind the detonation front inhibits the development of reflected shock wave bifurcation.

Robust near-threshold QDI circuit analysis and design

The two most important digital-system design goals today are to reduce power consumption and to increase reliability. Reductions in power consumption improve battery life in the mobile space and reductions in energy lower operating costs in the datacenter. Increased robustness and reliability shorten down time, improve yield, and are invaluable in the context of safety-critical systems. While optimizing towards these two goals is important at all design levels, optimizations at the circuit level have the furthest reaching effects; they apply to all digital systems. This dissertation presents a study of robust minimum-energy digital circuit design and analysis. It introduces new device models, metrics, and methods of calculation—all necessary first steps towards building better systems—and demonstrates how to apply these techniques. It analyzes a fabricated chip (a full-custom QDI microcontroller designed at Caltech and taped-out in 40-nm silicon) by calculating the minimum energy operating point and quantifying the chip’s robustness in the face of both timing and functional failures.

Magnetohydrodynamic turbulence

We simulate incompressible, MHD turbulence using a pseudo-spectral code. Our major conclusions are as follows.

1) MHD turbulence is most conveniently described in terms of counter propagating shear Alfvén and slow waves. Shear Alfvén waves control the cascade dynamics. Slow waves play a passive role and adopt the spectrum set by the shear Alfvén waves. Cascades composed entirely of shear Alfvén waves do not generate a significant measure of slow waves.

2) MHD turbulence is anisotropic with energy cascading more rapidly along k_⊥ than along k_∥, where k_⊥ and k_∥ refer to wavevector components perpendicular and parallel to the local magnetic field. Anisotropy increases with increasing k_⊥ such that excited modes are confined inside a cone bounded by k_∥ ∝ k^γ_⊥ where γ less than 1. The opening angle of the cone, θ(k_⊥) ∝ k^-(1-γ)_⊥, defines the scale dependent anisotropy.

3) MHD turbulence is generically strong in the sense that the waves which comprise it suffer order unity distortions on timescales comparable to their periods. Nevertheless, turbulent fluctuations are small deep inside the inertial range. Their energy density is less than that of the background field by a factor θ² (k_⊥)≪1.

4) MHD cascades are best understood geometrically. Wave packets suffer distortions as they move along magnetic field lines perturbed by counter propagating waves. Field lines perturbed by unidirectional waves map planes perpendicular to the local field into each other. Shear Alfvén waves are responsible for the mapping's shear and slow waves for its dilatation. The amplitude of the former exceeds that of the latter by 1/θ(k_⊥) which accounts for dominance of the shear Alfvén waves in controlling the cascade dynamics.

5) Passive scalars mixed by MHD turbulence adopt the same power spectrum as the velocity and magnetic field perturbations.

6) Decaying MHD turbulence is unstable to an increase of the imbalance between the flux of waves propagating in opposite directions along the magnetic field. Forced MHD turbulence displays order unity fluctuations with respect to the balanced state if excited at low k by δ(t) correlated forcing. It appears to be statistically stable to the unlimited growth of imbalance.

7) Gradients of the dynamic variables are focused into sheets aligned with the magnetic field whose thickness is comparable to the dissipation scale. Sheets formed by oppositely directed waves are uncorrelated. We suspect that these are vortex sheets which the mean magnetic field prevents from rolling up.

8) Items (1)-(5) lend support to the model of strong MHD turbulence put forth by Goldreich and Sridhar (1995, 1997). Results from our simulations are also consistent with the GS prediction γ = 2/3. The sole not able discrepancy is that the 1D power law spectra, E(k_⊥) ∝ k^-∝_⊥, determined from our simulations exhibit ∝ ≈ 3/2, whereas the GS model predicts ∝ = 5/3.