Norton-Thevenin Receptance Coupling (NTRC) as a Payload Design Tool

The NASA Engineering and Safety Center (NESC) is funding a study to develop an alternate method for performing coupled loads analysis called Norton-Thevenin Receptance Coupling (NTRC). NTRC combines Receptance Coupling (RC), a frequency-domain synthesis method and Norton-Thevenin (NT) theory, an impedance based approach for simulating the interaction between dynamic systems. The goal of developing the NTRC method is to provide a tool that payload developers can use to reduce the conservatism in defining preliminary design loads, assess the impact of design changes between formal load cycles, and to perform trade studies for design optimization with a minimum amount of data required from the launch vehicle (LV) provider. NTRC also has the ability to perform parametric loads analysis where many different design configurations can be evaluated. This will result in cost and schedule benefits to the payload developer that are currently not possible under the standard coupled loads analysis (CLA) flow where typically only 2-3 official load cycles are performed by the LV provider over the life of a payload program. NTRC is not envisioned as a replacement for the official load cycles performed by the LV provider but rather as a means to address the types of design issues faced by the payload developer before and between official load cycles.The presentation provides an overview of the NTRC methodology and discusses how NTRC can be used to replicate the results from a standard LV CLA. The presentation covers the benchmarking that has been performed as part of the NESC study to demonstrate the accuracy of the technique for both frequency and time domain dynamic analyses. Future plans for benchmarking the NTRC approach against CLA results for NASAs Space Launch System (SLS) and commercial launch vehicles are discussed and the role that NTRC is envisioned to play in the payload development cycle

Derivation of normal macrophages from human embryonic stem (hES) cells for applications in HIV gene therapy

BACKGROUND: Many novel studies and therapies are possible with the use of human embryonic stem cells (hES cells) and their differentiated cell progeny. The hES cell derived CD34 hematopoietic stem cells can be potentially used for many gene therapy applications. Here we evaluated the capacity of hES cell derived CD34 cells to give rise to normal macrophages as a first step towards using these cells in viral infection studies and in developing novel stem cell based gene therapy strategies for AIDS. RESULTS: Undifferentiated normal and lentiviral vector transduced hES cells were cultured on S17 mouse bone marrow stromal cell layers to derive CD34 hematopoietic progenitor cells. The differentiated CD34 cells isolated from cystic bodies were further cultured in cytokine media to derive macrophages. Phenotypic and functional analyses were carried out to compare these with that of fetal liver CD34 cell derived macrophages. As assessed by FACS analysis, the hES-CD34 cell derived macrophages displayed characteristic cell surface markers CD14, CD4, CCR5, CXCR4, and HLA-DR suggesting a normal phenotype. Tests evaluating phagocytosis, upregulation of the costimulatory molecule B7.1, and cytokine secretion in response to LPS stimulation showed that these macrophages are also functionally normal. When infected with HIV-1, the differentiated macrophages supported productive viral infection. Lentiviral vector transduced hES cells expressing the transgene GFP were evaluated similarly like above. The transgenic hES cells also gave rise to macrophages with normal phenotypic and functional characteristics indicating no vector mediated adverse effects during differentiation. CONCLUSION: Phenotypically normal and functionally competent macrophages could be derived from hES-CD34 cells. Since these cells are susceptible to HIV-1 infection, they provide a uniform source of macrophages for viral infection studies. Based on these results, it is also now feasible to transduce hES-CD34 cells with anti-HIV genes such as inhibitory siRNAs and test their antiviral efficacy in down stream differentiated cells such as macrophages which are among the primary cells that need to be protected against HIV-1 infection. Thus, the potential utility of hES derived CD34 hematopoietic cells for HIV-1 gene therapy can be evaluated

Detection of Extended Hot Water in the Outflow from NGC 2071

We report the results of spectroscopic mapping observations carried out toward a ~1 min x 1 min region within the northern lobe of the outflow from NGC 2071 using the Infrared Spectrograph (IRS) of the Spitzer Space Telescope. These observations covered the 5.2-37 um spectral region and have led to the detection of a number of ionic, atomic, and molecular lines, including fine-structure emission of Si+, Fe+, S++, S, the S(0)-S(7) pure rotational lines of H2, the R(3) and R(4) transitions of HD, and at least 11 transitions of H2O. In addition, the 6.2, 7.4, 7.6, 7.9, 8.6 and 11.3 um PAH emission bands were also observed and several transitions of OH were tentatively detected. Most of the detected line transitions were strong enough to map including, for the first time, three transitions of hot H2O. We find that: (1) the water emission is extended; (2) the extended emission is aligned with the outflow; and, (3) the spatial distribution of the water emission generally follows that observed for H2. Based on the measured line intensities, we derive an HD abundance relative to H2 of 1.1-1.8 10^-5 and an H2O number density of 12-2 cm^3. The H2 density in the water-emitting region is not well constrained by our observations, but is likely between 3 10^4 and 10^6 cm^3, yielding an H2O abundance relative to H2 of between 2 10^-5 and 6 10^-4. Future observations planned for the Herschel Space Observatory should greatly improve the density estimate, and thus our knowledge of the H2O abundance, for the water-emitting regions reported here. Finally, we note a possible departure from the H2O ortho-to-para ratio of 3:1 expected for water formed in hot post-shocked gas, suggesting that a significant fraction of the water vapor we detect may arise from H2O sputtered from cold dust grains.Comment: 35 pages, 15 figures, 4 tables, accepted for publication in Ap

Geometrical dissipation for dynamical systems

On a Riemannian manifold $(M,g)$ we consider the $k+1$ functions $F_1,...,F_k,G$ and construct the vector fields that conserve $F_1,...,F_k$ and dissipate $G$ with a prescribed rate. We study the geometry of these vector fields and prove that they are of gradient type on regular leaves corresponding to $F_1,...,F_k$. By using these constructions we show that the cubic Morrison dissipation and the Landau-Lifschitz equation can be formulated in a unitary form

Spitzer observations of hydrogen deuteride

We report the detection of interstellar hydrogen deuteride (HD) toward the supernova remnant IC443, and the tentative detection of HD toward the Herbig Haro objects HH54 and HH7 and the star forming region GGD37 (Cepheus A West). Our detections are based upon spectral line mapping observations of the R(3) and R(4) rotational lines of HD, at rest wavelengths of 28.502 and 23.034 micron respectively, obtained using the Infrared Spectrograph onboard the Spitzer Space Telescope. The HD R(4)/R(3) line intensity ratio promises to be a valuable probe of the gas pressure in regions where it can be observed. The derived HD/H2 abundance ratios are 1.19(+0.35/-0.24)E-5, 1.80(+0.54/-0.32)E-5, and 1.41(+0.46/-0.33)E-5 respectively (68.3% confidence limits, based upon statistical errors alone) for IC443 (clump C), HH54, and HH7. If HD is the only significant reservoir of gas-phase deuterium in these sources, the inferred HD/H2 ratios are all consistent with a gas-phase elemental abundance [n(D)/n(H)](gas) ~ 7.5E-6, a factor 2 - 3 below the values obtained previously from observations of atomic deuterium in the local bubble and the Galactic halo. However, similarly low gas-phase deuterium abundances have been inferred previously for molecular gas clouds in the Orion region, and in atomic clouds along sight-lines within the Galactic disk to stars more distant than 500 pc from the Sun.Comment: 12 pages, including 5 figures. Accepted for publication in ApJ Letter

Impacto social y clínico de las malformaciones urológicas congénitas en un país en desarrollo : la necesidad de un tratamiento transdisciplinario

Introducción. El pronóstico de las anomalías congénitas puede mejorarse si se detectan y tratan adecuadamente. Dada la complejidad de algunas anomalías, casi siempre es necesario abordarlas con un equipo interdisciplinario. Nuestro objetivo fue contactar a los pacientes con anomalías urológicas congénitas (CUA) con posterior seguimiento durante los primeros años de vida, se evaluó su estado clínico así como las limitaciones sociales y de atención médica. Método Basado en el Programa de Vigilancia de Malformaciones congénitas de Bogotá, contactamos por teléfono a todos los pacientes con CUA y evaluamos su seguimiento. Fueron incluidos todos los pacientes desde 2006 hasta 2015. Un cuestionario estandarizado fue aplicado por personal capacitado. Las preguntas evaluadas durante la llamada incluyeron: evaluación del estado clínico, tratamientos clínicos realizados y evaluaciones por subespecialidades clínicas y quirúrgicas, limitaciones de atención médica y barreras sociales. La primera llamada se realizó en el segundo mes y luego cada tres meses durante el primer año y luego cada 6 meses a partir de entonces. Resultados Se contactó a un total de 277 pacientes en los que el 97,3% tenía un riesgo de mortalidad o de discapacidad significativa. La mortalidad relacionada con la malformación fue del 38.1%. Solo el 38,7% de los pacientes fueron evaluados por un especialista, mientras que el 57,4% aún esperaban ser atendidos por un especialista. El noventa y ocho por ciento de las limitaciones relacionadas con el sistema de atención fueron las largas listas de espera para ser visto por un especialista. Conclusión Muchas de las patologías pertenecen al grupo que cuando son tratadas adecuadamente y prontamente tienen una reducción significativa en la mortalidad. Sin embargo, tenemos un problema profundo en nuestro sistema de atención médica donde muchos de los pacientes no han sido atendidos por un especialista, lo que resulta en un peor pronóstico y tasa de recuperación.Q4Artículo original285-290Introduction. The prognosis of congenital anomalies (CAs) can be improved if detected and treated accurately. Given the complexity of some anomalies, it is almost always necessary to approach them with an interdisciplinary team. Our objective was to contact patients with congenital urological anomalies (CUAs) and follow them up during their first years of life and evaluate their clinical status, as well as their social and health care limitations. Method Based on the Bogota Congenital Malformations Surveillance Program (BCMSP), we have contacted by phone all the patients with CUAs and evaluated their follow-up. We have included all the registered patients from 2006 until 2015. A standardized questionnaire was applied by a trained staff. The questions assessed on each call included: evaluation of the clinical status of the patient, the clinical treatments and evaluations performed by clinical and surgical subspecialties, health care limitations, and social barriers. The first call was made at the 2nd month, then every 3 months during the 1st year and every 6 months thereafter. Results A total of 277 patients were contacted, 97.3% of whom have an increased risk of mortality or significant disability. The malformation related mortality was of 38.1%. Only 38.7% of the patients were evaluated by a specialist, while 57.4% where still waiting to be seen by a specialist. Ninety eight percent of the limitations related to the health care system were the long waiting lists to be seen by a specialist. Conclusion Many of the pathologies that we have found belong to the group that has a significant reduction in mortality when treated accurately and promptly. However, we have a profound problem in our health care system, in that many of the patients have not been seen by a specialist, which results in a worse prognosis and recovery rate

Long-term Death Rates, West Nile Virus Epidemic, Israel, 2000

We studied the 2-year death rate of 246 adults discharged from hospital after experiencing acute West Nile Virus infection in Israel during 2000. The age- and sex-adjusted death rates were significantly higher than in the general population. This excess was greater for men. Significant adverse prognostic factors were age, male sex, diabetes mellitus, and dementia

Nutritional supplements in chronic kidney disease

Introducción: El estado nutricional de los pacientes con enfermedad renal crónica (ERC) influye sobre el progreso de la enfermedad y se asocia al incremento en el riesgo cardiovascular. Revisamos en la literatura el efecto de los suplementos nutricionales en estos pacientes. Métodos: Se realizó una búsqueda de la literatura en las bases de datos electrónicas Pubmed y Embase para encontrar estudios clínicos que relacionaran el efecto de los suplementos y/o complementos nutricionales con ERC. Resultados: De 353 artículos que resultaron inicialmente, se seleccionaron 26, de los cuales 23 fueron realizados en población con falla renal. En los pacientes con suplencia, se reportaron efectos como disminución en los niveles de homocisteína tras la administración de zinc, omega-3 y ácido fólico. Adicionalmente, se evidenció disminución en los metabolitos de estrés oxidativo. Con la terapia de suplementación con vitamina D se observó mejoría en el perfil lipídico y diminución en hemoglobina glicosilada y PCR. Discusión: Los suplementos y/o complementos nutricionales compuestos por probióticos, ácidos grasos de cadena larga (omega-3), proteínas, elementos de traza, antioxidantes y ácido fólico podrían ser de importancia en pacientes con ERC ante los efectos benéficos que han demostrado tener, por la reducción en la homocisteína y otros factores derivados del estrés oxidativo considerados marcadores de riesgo cardiovascular, o también por disminuirse la prevalencia de malnutrición en esta población. Los estudios sugieren que los suplementos y/o complementos nutricionales podrían retrasar el deterioro renal progresivo y reducir los marcadores de riesgo cardiovascular, principalmente en aquellos compuestos por omega-3.Completo89-98Introduction: The nutritional status of patients with chronic kidney disease (CKD) affects the progress of the disease and is associated with increased cardiovascular risk. We reviewed the literature in search of the effect of nutritional supplements in these patients.Methods: Our search included the electronic databases Pubmed and Embase and was structured to find clinical studies relating the effect of supplements and/or nutritional supplements with CKD.Results: In total the search resulted in 353 articles, 26 were selected, of which 23 were performed in people with kidney failure. In patients with supplements, effects such as decrease in homocysteine levels after administration of zinc, omega-3 and folic acid were reported. Addi-tionally, reduction was observed in the metabolites of oxidative stress. In therapy with vitamin D supplementation resulted in improvements in the lipid profile and reduction in the levels of glycated hemoglobin and PCR.Discussion: Supplements and/or nutritional compliments with compounds probiotics, long chain fatty acids (omega-3), proteins, trace ele-ments, antioxidants and folic acid; Could be relevant in patients with CKD because they have demonstrated positive effects such as reducing homocysteine and other factors caused by oxidative stress, and in reducing the prevalence of malnutrition in this population. Studies suggest that supplements and/or nutritional compliments may delay progressive renal deterioration and decrease cardiovascular risk markers, main-ly those supplements composed by omega-3

Expression of a Recombinant High Affinity IgG Fc Receptor by Engineered NK Cells as a Docking Platform for Therapeutic mAbs to Target Cancer Cells

Anti-tumor mAbs are the most widely used and characterized cancer immunotherapy. Despite having a significant impact on some malignancies, most cancer patients respond poorly or develop resistance to this therapy. A known mechanism of action of these therapeutic mAbs is antibody-dependent cell-mediated cytotoxicity (ADCC), a key effector function of human NK cells. CD16A on human NK cells has an exclusive role in binding to tumor-bound IgG antibodies. Though CD16A is a potent activating receptor, it is also a low affinity IgG Fc receptor (FcγR) that undergoes a rapid downregulation in expression by a proteolytic process involving ADAM17 upon NK cell activation. These regulatory processes are likely to limit the efficacy of tumor-targeting therapeutic mAbs in the tumor environment. We sought to enhance NK cell binding to anti-tumor mAbs by engineering these cells with a recombinant FcγR consisting of the extracellular region of CD64, the highest affinity FcγR expressed by leukocytes, and the transmembrane and cytoplasmic regions of CD16A. This novel recombinant FcγR (CD64/16A) was expressed in the human NK cell line NK92 and in induced pluripotent stem cells from which primary NK cells were derived. CD64/16A lacked the ADAM17 cleavage region in CD16A and it was not rapidly downregulated in expression following NK cell activation during ADCC. CD64/16A on NK cells facilitated conjugation to antibody-treated tumor cells, ADCC, and cytokine production, demonstrating functional activity by its two components. Unlike NK cells expressing CD16A, CD64/16A captured soluble therapeutic mAbs and the modified NK cells mediated tumor cell killing. Hence, CD64/16A could potentially be used as a docking platform on engineered NK cells for therapeutic mAbs and IgG Fc chimeric proteins, allowing for switchable targeting elements and a novel cancer cellular therapy