State convergence and the effectiveness of time-memory-data tradeoffs

Various time-memory tradeoffs attacks for stream ciphers have been proposed over the years. However, the claimed success of these attacks assumes the initialisation process of the stream cipher is one-to-one. Some stream cipher proposals do not have a one-to-one initialisation process. In this paper, we examine the impact of this on the success of time-memory-data tradeoff attacks. Under the circumstances, some attacks are more successful than previously claimed while others are less. The conditions for both cases are established.

Cetuximab plus chemotherapy in patients with advanced non-small-cell lung cancer (FLEX) : an open-label randomised phase III trial

Background: Use of cetuximab, a monoclonal antibody targeting the epidermal growth factor receptor (EGFR), has the potential to increase survival in patients with advanced non-small-cell lung cancer. We therefore compared chemotherapy plus cetuximab with chemotherapy alone in patients with advanced EGFR-positive non-small-cell lung cancer. Methods: In a multinational, multicentre, open-label, phase III trial, chemotherapy-naive patients (≥18 years) with advanced EGFR-expressing histologically or cytologically proven stage wet IIIB or stage IV non-small-cell lung cancer were randomly assigned in a 1:1 ratio to chemotherapy plus cetuximab or just chemotherapy. Chemotherapy was cisplatin 80 mg/m 2 intravenous infusion on day 1, and vinorelbine 25 mg/m 2 intravenous infusion on days 1 and 8 of every 3-week cycle) for up to six cycles. Cetuximab-at a starting dose of 400 mg/m 2 intravenous infusion over 2 h on day 1, and from day 8 onwards at 250 mg/m 2 over 1 h per week-was continued after the end of chemotherapy until disease progression or unacceptable toxicity had occurred. The primary endpoint was overall survival. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00148798. Findings: Between October, 2004, and January, 2006, 1125 patients were randomly assigned to chemotherapy plus cetuximab (n=557) or chemotherapy alone (n=568). Patients given chemotherapy plus cetuximab survived longer than those in the chemotherapy-alone group (median 11·3 months vs 10·1 months; hazard ratio for death 0·871 [95% CI 0·762-0·996]; p=0·044). The main cetuximab-related adverse event was acne-like rash (57 [10%] of 548, grade 3). Interpretation: Addition of cetuximab to platinum-based chemotherapy represents a new treatment option for patients with advanced non-small-cell lung cancer. Funding: Merck KGaA. © 2009 Elsevier Ltd. All rights reserved.

A robot application to marine vessel inspection

Seagoing vessels have to undergo regular inspections, which are currently performed manually by ship surveyors. The main cost factor in a ship inspection is to provide access to the different areas of the ship, since the surveyor has to be close to the inspected parts, usually within arm's reach, either to perform a visual analysis or to take thickness measurements. The access to the structural elements in cargo holds, e.g., bulkheads, is normally provided by staging or by 'cherry-picking' cranes. To make ship inspections safer and more cost-efficient, we have introduced new inspection methods, tools, and systems, which have been evaluated in field trials, particularly focusing on cargo holds. More precisely, two magnetic climbing robots and a micro-aerial vehicle, which are able to assist the surveyor during the inspection, are introduced. Since localization of inspection data is mandatory for the surveyor, we also introduce an external localization system that has been verified in field trials, using a climbing inspection robot. Furthermore, the inspection data collected by the robotic systems are organized and handled by a spatial content management system that enables us to compare the inspection data of one survey with those from another, as well as to document the ship inspection when the robot team is used. Image-based defect detection is addressed by proposing an integrated solution for detecting corrosion and cracks. The systems' performance is reported, as well as conclusions on their usability, all in accordance with the output of field trials performed onboard two different vessels under real inspection conditions.

C-H…O hydrogen bond mediated chain reversal in a peptide containing g-amino acid residue, determined directly from powder X-ray diffraction data

The finding that peptides containing -amino acid residues give rise to folding patterns hitherto unobserved in -amino acid peptides[1] has stimulated considerable interest in the conformational properties of peptides built from , and residues,[2] as the introduction of additional methylene (CH2) units into peptide chains provides further degrees of conformational freedom.

Why Is Less Cationic Lipid Required To Prepare Lipoplexes from Plasmid DNA than Linear DNA in Gene Therapy?

The most important objective of the present study was to explain why cationic lipid (CL)-mediated delivery of plasmid DNA (pDNA) is better than that of linear DNA in gene therapy, a question that, until now, has remained unanswered. Herein for the first time we experimentally show that for different types of CLs, pDNA, in contrast to linear DNA, is compacted with a large amount of its counterions, yielding a lower effective negative charge. This feature has been confirmed through a number of physicochemical and biochemical investigations. This is significant for both in vitro and in vivo transfection studies. For an effective DNA transfection, the lower the amount of the CL, the lower is the cytotoxicity. The study also points out that it is absolutely necessary to consider both effective charge ratios between CL and pDNA and effective pDNA charges, which can be determined from physicochemical experiments.

How Does the Spacer Length of Cationic Gemini Lipids Influence the Lipoplex Formation with Plasmid DNA? Physicochemical and Biochemical Characterizations and their Relevance in Gene Therapy

Lipoplexes formed by the pEGFP-C3 plasmid DNA (pDNA) and lipid mixtures containing cationic gemini surfactant of the 1,2-bis(hexadecyl dimethyl ammonium) Acmes family referred to as C16CnC16, where n = 2 3, 5, or 12, and the zwitterionic helper lipid, 1,2-dioleoyl-sn-glycero-3-phosphatidylethanolamine (DOPE) have been studied from a wide variety of physical, chemical, and biological standpoints. The study has been carried out using several experimental methods, such as zeta potential, gel electrophoresis, small-angle X-ray scattering (SAXS), cryo-TEM, gene transfection, cell viability/cytotoxicity, and confocal fluorescence microscopy. As reported recently in a communication (J. Am. Chem. Soc. 2011, 133, 18014), the detailed physicochemical and biological studies confirm that, in the presence of the studied series lipid mixtures, plasmid DNA is compacted with a large number of its associated Na+ counterions. This in turn yields a much lower effective negative charge, q(pDNA)(-), a value that has been experimentally obtained for each mixed lipid mixture. Consequently, the cationic lipid (CL) complexes prepared with pDNA and CL/DOPE mixtures to be used in gene transfection require significantly less amount of CL than the one estimated assuming a value of q(DNA)(-) = -2. This drives to a considerably lower cytotoxicity of the gene vector. Depending on the CL molar composition, alpha, of the lipid mixture, and the effective charge ratio of the lipoplex, rho(eff), the reported SAXS data indicate the presence of two or three structures in the same lipoplex, one in the DOPE-rich region, other in the CL-rich region, and another one present at any CL composition. Cryo-TEM and SAXS studies with C16CnC16/DOPE-pDNA lipoplexes indicate that pDNA is localized between the mixed lipid bilayers of lamellar structures within a monolayer of similar to 2 nm. This is consistent with a highly compacted supercoiled pDNA conformation compared with that of linear DNA. Transfection studies were carried out with HEK293T, HeLa, CHO, U343, and H460 cells. The alpha and rho(eff) values for each lipid mixture were optimized on HEK293T cells for transfection, and using these values, the remaining cells were also transfected in absence (-FBS-FBS) and presence (-FBS+FBS) of serum. The transfection efficiency was higher with the CLs of shorter gemini spacers (n = 2 or 3). Each formulation expressed GFP on pDNA transfection and confocal fluorescence microscopy corroborated the results. C16C2C16/DOPE mixtures were the most efficient toward transfection among all the lipid mixtures and, in presence of serum, even better than the Lipofectamine2000, a commercial transfecting agent Each lipid combination was safe and did not show any significant levels of toxicity. Probably, the presence of two coexisting lamellar structures in lipoplexes synergizes the transfection efficiency of the lipid mixtures which are plentiful in the lipoplexes formed by CLs with short spacer (n = 2, 3) than those with the long spacer (n = 5, 12).

Effects of a Delocalizable Cation on the Headgroup of Gemini Lipids on the Lipoplex-Type Nanoaggregates Directly Formed from Plasmid DNA

Lipoplex-type nanoaggregates prepared from pEGFP-C3 plasmid DNA (pDNA) and mixed liposomes, with a gemini cationic lipid (CL) 1,2-bis(hexadecyl imidazolium) alkanes], referred as (C(16)Im)(2)C-n (where C-n is the alkane spacer length, n = 2, 3, 5, or 12, between the imidazolium heads) and DOPE zwitterionic lipid, have been analyzed by zeta potential, gel electrophoresis, SAXS, cryo-TEM, fluorescence anisotropy, transfection efficiency, fluorescence confocal microscopy, and cell viability/cytotoxicity experiments to establish a structure-biological activity relationship. The study, carried out at several mixed liposome compositions, alpha, and effective charge ratios, rho(eff), of the lipoplex, demonstrates that the transfection of pDNA using CLs initially requires the determination of the effective charge of both. The electrochemical study confirms that CLs with a delocalizable positive charge in their headgroups yield an effective positive charge that is 90% of their expected nominal one, while pDNA is compacted yielding an effective negative charge which is only 10-25% than that of the linear DNA. SAXS diffractograms show that lipoplexes formed by CLs with shorter spacer (n = 2, 3, or 5) present three lamellar structures, two of them in coexistence, while those formed by CL with longest spacer (n = 12) present two additional inverted hexagonal structures. Cryo-TEM micrographs show nanoaggregates with two multilamellar structures, a cluster-type (at low alpha value) and a fingerprint-type, that coexist with the cluster-type at moderate alpha composition. The optimized transfection efficiency (TE) of pDNA, in HEK293T, HeLa, and H1299 cells was higher using lipoplexes containing gemini CLs with shorter spacers at low a value. Each lipid formulation did not show any significant levels of toxicity, the reported lipoplexes being adequate DNA vectors for gene therapy and considerably better than both Lipofectamine 2000 and CLs of the 1,2-bis(hexadecyl ammnoniun) alkane series, recently reported.

Cationic gemini lipids containing polyoxyethylene spacers as improved transfecting agents of plasmid DNA in cancer cells

Lipoplex nano-aggregates have been analyzed through biophysical characterization (electrostatics, structure, size and morphology), and biological studies (transfection efficiency and cell viability) in five cancer cell lines. Lipoplexes were prepared from pEGFP-C3 plasmid DNA (pDNA) and mixed liposomes, constituted by a zwitterionic lipid (DOPE) and a gemini cationic lipid (GCL) synthesized in this work, bis(hexadecyl dimethyl ammonium) oxyethylene], referred to as (C16Am)(2)(C2O)(n), (where n is the oxyethylene spacer length, n = 1, 2 or 3, between the ammonium heads). Cryo-TEM micrographs show nano-aggregates with two multilamellar structures, a cluster-type (at low-to-medium GCL composition) and a fingerprint-type that coexists with the cluster-type at medium GCL composition and appears alone at high GCL composition. SAXS diffractograms show that these lipoplexes present three lamellar structures, two of them coexisting at low and high GCL composition. The optimized transfection efficiency (TE) of pDNA was higher for lipoplexes containing GCLs with a longer (n = 3) or shorter (n = 1) polyoxyethylene spacer, at high GCL composition (alpha - 0.7) with low charge ratio (rho(eff) 2). In the all cancer cell lines studied, the TE of the optimized formulations was much better than those of both lipofectamine 2000 and lipoplexes with GCLs of the bis(hexadecyl dimethyl ammonium) alkane series recently reported. Probably, (a) the coexistence of two lamellar structures at high GCL composition synergizes the TE of these lipid vectors, (b) the orientation of the polyoxyethylene region in (C16Am)(2)(C2O)(3)/DOPE may occur in such a way that the spacing between two cationic heads becomes smaller than that in (C16Am)(2)(C2O)(2)/DOPE which is poor in terms of TE, and (c) the synergistic interactions between serum proteins and (C16Am)(2)(C2O)(n)/DOPE-pDNA lipoplexes containing a polyoxyethylene spacer improve TE, especially at high GCL content. Lipoplexes studied here show very low levels of toxicity, which confirm them as improved vectors of pDNA in gene therapy.

A delocalizable cationic headgroup together with an oligo-oxyethylene spacer in gemini cationic lipids improves their biological activity as vectors of plasmid DNA

Lipoplex nano-aggregates constituted of plasmid DNA (pDNA) pEGFP-C3 and mixed cationic liposomes, consisting of several percentages of a gemini cationic lipid (GCL) of the 1,2-bis(hexadecyl imidazolium) oxyethylene series, referred to as (C(16)Im)(2)(C2O)(n), with oxyethylene spacers (n = 1, 2 or 3) between the imidazolium cationic groups and the DOPE zwitterionic helper lipid, have been characterized by various biophysical and biological approaches carried out at several GCL compositions (alpha), and either the mass or the effective charge ratio of the lipoplex. The electrochemical study by zeta-potential confirms that the three GCLs yield a 10% lower effective charge than the nominal one, while compacted pDNA yields only a 25% effective negative charge. The SAXS study reveals, irrespective of the spacer length (n) and effective charge ratio (rho(eff)), the presence of two lamellar structures, i.e., one (L-alpha,L-main) in the whole GCL composition and another (L-alpha,L-DOPE,L-rich) with higher periodicity values that coexists with the previous one at low GCL composition (alpha = 0.2). The cryo-TEM analysis shows two types of multilamellar structures consisting of cationic lipidic bilayers with pDNA sandwiched between them: a cluster-type (C-type) at low alpha = 0.2 and a fingerprint-type (FP-type) at alpha >= 0.5, both with similar interlamellar spacing (d) in agreement with the L-alpha,L-main structure determined by SAXS. Transfection efficacies (TEs) of each lipid mixture were determined in four different cell lines (HEK293T, HeLa, Caco-2 and A549) at several alpha and rho(eff) values in the absence and presence of serum (FBS). The optimized formulations (alpha = 0.2 and rho(eff) = 2.0) substantially transfect cells much better than a commercial transfection reagent, Lipofectamine 2000 and previously studied efficient lipoplexes containing other cationic head groups or spacers both in the absence and presence of serum. The activity of optimized formulations may be attributed to the combination of several factors, such as: (a) the fusogenic character of DOPE which results in higher fluidity of the lipoplexes at alpha = 0.2, (b) the coexistence of two lamellar structures at alpha = 0.2 that synergizes the TE of these lipid vectors, and mainly (c) the higher biocompatibility of the GCLs reported in this work due to the presence of two imidazolium cationic groups together with an oligo-oxyethylene spacer. The length of the spacer in the GCL seems to have less impact, although (C(16)Im)(2)(C2O)(n)/DOPEpDNA lipoplexes with n = 1 and 3 show higher gene transfection than n = 2. All the optimum formulations reported herein are all highly efficient with negligible levels of toxicity, and thus, may be considered as very promising gene vectors for in vivo applications.

Arreglos de siembra de frijol común (Phaseolus vulgaris L.) y maiz (Zea mays L.) en asocio y monocultivos, efecto sobre la cenosis, crecimiento y rendimiento de los cultivos y uso equivalente de la tierra

En el presente escrito se presentan los resultados de un experimento sembrado en la época de primera 1994, en la finca experimental La Compañía, ubicada en el municipio de San Marcos, departamento de Carazo, en un suelo de origen volcánico con altos contenidos de carbono orgánico. El propósito fue determinar el efecto de siembra de frijol común (Phaseolus vulgaris L.) Asociado con maíz (Zea mays L.) Y monocultivos sobre la dinámica de las malezas, utilidad de la tierra y rendimiento de los cultivos. Se utilizó un diseño de bloques completos al azar con cuatro repeticiones en el cual se evaluaron monocultivo de maíz y frijol, y la asociación de frijol con maíz bajo 4 arreglos de siembra: un surco de frijol y 1 de maíz (1:1), dos surcos de frijol y uno de maíz (2:1), tres surcos de frijol y uno de maíz (3:1) y cuatro surcos de frijol y uno de maíz (4:1). Los resultados obtenidos indican que los asocios resultaron ser más eficientes que los monocultivos sobre la abundancia y dominancia de las malezas al aprovechar estos el efecto de cobertura que ejerció el frijol en las calles de maíz, reduciendo de esta forma las necesidades de control principalmente en lo referente a este último. Los mayores rendimientos de grano se obtuvieron también en los sistemas asociados bajo los arreglos 2:1, .3: l, 4:1 y 1:1, seguidos por el monocultivo de maíz. El frijol en monocultivo fue el menos rendidor por unidad de área. En cuanto a la eficiencia en el uso de la tierra fue mayor en los asocios que en los monocultivos, los cuales tuvieron un uso equivalente de la tierra (UET) de 1.64, 1.51, 1.43 y 1.30 para los arreglos 3: l, 4:1, 2:1 y 1:1 respectivamente, proporcionando un 64, 51, 43 y 30 por ciento más de producción por unidad de área que los monocultivos. El policultivo resultó ser un componente valioso a ser tomado en cuenta en un programa de manejo integrado de malezas en ambos cultivos, ya que reduce la vulnerabilidad del sistema a la colonización y establecimiento de las malezas, además de un mejor uso de la tierra y mayor diversificación de la producción.

Dinámica de la renovación y fomento cafetalero en el municipio de San Ramón, Matagalpa período 1990-1995

El presente trabajo fue realizado durante los meses de enero a agosto de 1996, en el municipio de San Ramón departamento de Matagalpa VI Región de Nicaragua, con el objetivo de conocer la dinámica de la renovación y fomento de café (Coffea arabíca L.) en el periodo 1990-1995, a nivel general y por tipo de productor, sus problemáticas y posibles alternativas. El diseno muestra! usado fue el probabilistico, donde todos los elementos tienen la misma posibilidad de ser seleccionados para el estudio, particularmente se utilizó el muestreo aleatorio estratificado no proporciona, se fijó el 10 por ciento de la muestra basado en criterio de Sequeira (1994) & Doorman (1991). Primero se realizó una encuesta a nivel de base y luego por medio razonado, estudios de casos. Los análisis realizados a los datos fueron por medios computarizados y de forma manual, obteniendo frecuencias porcentajes, medias, rango, encontrádose cuatro tipo de productores, campesinos cafetaleros, finqueros cafetaleros, empresarios cafetaleros y empresas asociativas. Según la muestra el 65.9 porciento de los productores están renovando y/o fomentando sus cafetales, el 31.5 porciento que no esta renovando, pertenecen a los tipos campesinos y finqueros, las variedades usadas son Caturra, Catimor y Bourbón, con densidades de 5 000, 5 000 y 3 333 plantas/mz respectivamente. Los costos de la renovación y fomento varían entre los tipos de productores, siendo los campesinos cafetaleros quienes tienen mas bajos costos, aumentando para los finqueros cafetaleros, empresarios cafetaleros y su máxima expresión en la empresa asociativa. Los principales problemas encontrados en la renovación son el poco e inadecuado crédito, débil asistencia técnica, seguridad jurídica y personal, en el orden técnico, fechas inadecuadas de establecimiento de vivero, semillero, terreno definitivo y uso de semilla no certificada.

Efecto de tres niveles de nitrógeno en el cultivo de arroz (Oryza sativa L.) con cinco líneas promisorias en la localidad de Malacatoya, bajo el sistema de riego por inundación

El presente estudio se realizó en la Empresa Agropecuaria Las Lajas, en el municipio de Malacatoya, departamento de Granada. El propósito del ensayo fue evaluar el efecto de tres niveles de nitrógeno con cinco líneas promisorias de arroz bajo el sistema de riego por inundación. El trabajo de campo estuvo comprendido entre el 19 de abril y el 12 de agosto de 1996. Para dicho trabajo se utilizó el diseño experimental de bloques completos al azar (BCA), con 15 tratamientos y 3 repeticiones. Se evaluaron 8 variables: Altura, volcamiento, longitud de panícula, panículas por metro cuadrado, número de granos, fertilidad de espiguillas peso de 1000 granos, además del rendimiento. Como resultado de la evaluación en las características agronómicas, componentes del rendimiento y rendimiento agrícola se seleccionaron dos líneas con buen rendimiento y buenas características agronómicas. Estas fueron la línea 203 con el primer nivel de que corresponde a 74.2 kg/ha de nitrógeno y la línea IG-2282 con el tercer nivel equivalente a 104 kg/ha de nitrógeno, la línea 203 con 74.2 kg/ha de nitrógeno obtuvo escala 1 de volcamiento y la línea IG-2282 con 104 kg/ha de nitrógeno presentó escala 3 de volcamiento; escala de volcamiento aceptada comercialmente.

La problemática del cambio en los proyectos de desarrollo para S. C. de Bariloche : (1930- 1943)

El objetivo principal es analizar las diferentes concepciones en torno al cambio en el ámbito local y regional de San Carlos de Bariloche durante la década considerada paradigmática por la historiografía general, esto es la de la década de 1930, período que contiene la llegada de la institución que se erige como marca de identidad local, la Dirección de Parques Nacionales (en adelante, DPN). Para esto se plantean los siguientes objetivos específicos: a) Diseñar una indagación desde tres perspectivas: la del Estado Nacional, materializada en la presencia de Parques Nacionales1 y su primer presidente Exequiel Bustillo; la de la localidad barilochense, encarnada en la figura del Ingeniero Emilio Frey; y la del coronel José María Sarobe, quien trae a colación una visión regional patagónica integral a la luz de proyectos de desarrollo precedentes. b) Realizar un relevamiento de fuentes vinculadas a estas tres perspectivas que abrevan en: memorias personales, publicaciones oficiales, documentación local, prensa y publicaciones específicas en torno a la región. c) Analizar cada conjunto de fuentes. d) Integrar las distintas perspectivas a fin de avanzar hacia un análisis complejo de la problemática.