Propuesta de mejora del proceso de elaboración de jarabe simple en la Compañía Aje Colombia

El siguiente trabajo es presentado para optar por el título de “Especialistas en producción y logística internacional"; esta investigación tiene como principal propósito obtener mejoras en el proceso de elaboración de jarabe simple en la empresa AJE COLOMBIA, ya que se evidencian falencias en el mismo por temas de desperdicio, desorganización, fallas en el proceso y posibles riesgos a corto plazo en salud ocupacional. Se desarrollará la descripción y el análisis del proceso actual, se tienen en cuenta la maquinaria utilizada, las personas que se encuentran vinculadas directamente con el proceso y los movimientos realizados, dicho análisis guiara a la compañía hacia alternativas de solución que fomenten el mejoramiento del proceso. Para dar solución a estos problemas se debe indagar y observar que complicaciones se ven en el proceso que afectan la productividad y eficiencia, analizar con aportes de los profesionales a cargo, entrevistar a las personas involucradas directa e indirectamente en el proceso y conocer su opinión. Una vez se tengan identificados los problemas se analizarán las causas para llegar a una solución que satisfaga las necesidades corporativas y del proceso formulando conclusiones que aporten a la empresa una visión general para la automatización del proceso y eficiencia del mismo.The following work is presented to choose for the title of " Specialists in production and international logistics "; this investigation has as principal intention obtain improvements in the process of production of simple syrup in the company I RUFFLED COLOMBIA, since failings are demonstrated in the same one by topics of waste, disorganization, faults in the process and possible short-term risks in occupational health. There develops the description and the analysis of the current process, the used machinery is born in mind, the persons who are linked directly by the process and the realized movements, the above mentioned analysis was guiding to the company towards alternatives of solution that promote the improvement of the process. To give solution to these problems it is necessary to investigate and observe that complications are seen in the process that the productivity and efficiency affect, to analyze with contributions of the professionals to post, to interview the involved persons directly and indirectly in the process and to know his opinion. Once the problems are had identified the reasons will be analyzed to come to a solution that satisfies the corporate needs and of the process formulating conclusions that contribute to the company a general vision for the automation of the process and efficiency of the same one.Resumen 7 Introducción 8 1 Título de la investigación 9 2 Problema de investigación 9 21 Descripción del problema 9 22 Planteamiento del problema 11 23 Sistematización del problema 11 3 Objetivos de la investigación 12 31 Objetivo general 12 32 Objetivos específicos 12 4 Justificación y delimitación 12 41 Justificación 12 42 Delimitación 14 43 Limitaciones 14 5 Marco referencial 15 51 Estado del arte 15 511 Estado del arte local 15 512 Estado del arte nacional 16 513 Estado del arte internacional 18 52 Marco teórico 20 53 Marco histórico 32 54 Marco legal 34 6 Marco metodológico 36 61 Recolección de la información (metodología) 36 611 Tipo de investigación 36 612 Establecer fuentes de recolección de la información 36 6121 Fuentes primarias 36 6122 Fuentes secundarias 37 613 Herramientas a utilizar 37 614 Metodología 37 615 Recopilación de la información 37 62 Análisis de la información 43 63 Propuestas de solución 49 631 Propuesta 1 49 632 Propuesta 2 53 633 Propuesta 3 54 7 Resultados esperados 54 8 Análisis financieros (ROI) 56 9 Conclusiones y recomendaciones 58 91 Conclusiones 58 10 Bibliografía 60EspecializaciónEspecialista en Producción y Logística InternacionalEspecialización en Producción y Logística Internaciona

A novel European H5N8 influenza A virus has increased virulence in ducks but low zoonotic potential

We investigated in a unique setup of animal models and a human lung explant culture biological properties, including zoonotic potential, of a representative 2016 highly pathogenic avian influenza virus (HPAIV) H5N8, clade 2.3.4.4 group B (H5N8B), that spread rapidly in a huge and ongoing outbreak series in Europe and caused high mortality in waterfowl and domestic birds. HPAIV H5N8B showed increased virulence with rapid onset of severe disease and mortality in Pekin ducks due to pronounced neuro- and hepatotropism. Cross-species infection was evaluated in mice, ferrets, and in a human lung explant culture model. While the H5N8B isolate was highly virulent for Balb/c mice, virulence and transmissibility were grossly reduced in ferrets, which was mirrored by marginal replication in human lung cultures infected ex vivo. Our data indicate that the 2016 HPAIV H5N8B is avian-adapted with augmented virulence for waterfowl, but has low zoonotic potential. The here tested combination of animal studies with the inoculation of human explants provides a promising future workflow to evaluate zoonotic potential, mammalian replication competence and avian virulence of HPAIV.Peer Reviewe

Phage capsid nanoparticles with defined ligand arrangement block influenza virus entry

Multivalent interactions at biological interfaces occur frequently in nature and mediate recognition and interactions in essential physiological processes such as cell-to-cell adhesion. Multivalency is also a key principle that allows tight binding between pathogens and host cells during the initial stages of infection. One promising approach to prevent infection is the design of synthetic or semisynthetic multivalent binders that interfere with pathogen adhesion1,2,3,4. Here, we present a multivalent binder that is based on a spatially defined arrangement of ligands for the viral spike protein haemagglutinin of the influenza A virus. Complementary experimental and theoretical approaches demonstrate that bacteriophage capsids, which carry host cell haemagglutinin ligands in an arrangement matching the geometry of binding sites of the spike protein, can bind to viruses in a defined multivalent mode. These capsids cover the entire virus envelope, thus preventing its binding to the host cell as visualized by cryo-electron tomography. As a consequence, virus infection can be inhibited in vitro, ex vivo and in vivo. Such highly functionalized capsids present an alternative to strategies that target virus entry by spike-inhibiting antibodies5 and peptides6 or that address late steps of the viral replication cycle

Validation of Melanoma Immune Profile (MIP), a Prognostic Immune Gene Prediction Score for Stage II–III Melanoma

Purpose: Biomarkers are needed to stratify patients with stage II–III melanoma for clinical trials of adjuvant therapy because, while immunotherapy is protective, it also confers the risk of severe toxicity. We previously defined and validated a 53-immune gene melanoma immune profile (MIP) predictive both of distant metastatic recurrence and of disease-specific survival (DSS). Here, we test MIP on a third independent population. Experimental Design: A retrospective cohort of 78 patients with stage II–III primary melanoma was analyzed using the NanoString assay to measure expression of 53 target genes, and MIP score was calculated. Statistical analysis correlating MIP with DSS, overall survival, distant metastatic recurrence, and distant metastasis-free interval was performed using ROC curves, Kaplan–Meier curves, and standard univariable and multivariable Cox proportional hazards models. Results: MIP significantly distinguished patients with distant metastatic recurrence from those without distant metastatic recurrence using ROC curve analysis (AUC = 0.695; P = 0.008). We defined high- and low-risk groups based on the cutoff defined by this ROC curve and find that MIP correlates with both DSS and overall survival by ROC curve analysis (AUC = 0.719; P = 0.004 and AUC = 0.698; P = 0.004, respectively). Univariable Cox regression reveals that a high-risk MIP score correlates with DSS (P = 0.015; HR = 3.2). Conclusions: MIP identifies patients with low risk of death from melanoma and may constitute a clinical tool to stratify patients with stage II–III melanoma for enrollment in clinical trials

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

The RNA Helicase DDX6 Associates with RIG-I to Augment Induction of Antiviral Signaling

Virus infections induce sensitive antiviral responses within the host cell. The RNA helicase retinoic acid-inducible gene I (RIG-I) is a key sensor of influenza virus RNA that induces the expression of antiviral type I interferons. Recent evidence suggests a complex pattern of RIG-I regulation involving multiple interactions and cellular sites. In an approach employing affinity purification and quantitative mass spectrometry, we identified proteins with increased binding to RIG-I in response to influenza B virus infection. Among them was the RIG-I related RNA helicase DEAD box helicase 6 (DDX6), a known component of cytoplasmic mRNA-ribonucleoprotein (mRNP) granules like P-bodies and stress granules (SGs). RIG-I and DDX6 both localized to the cytosol and were detected in virus-induced SGs. Coimmunoprecipitation assays detected a basal level of complexes harboring RIG-I and DDX6 that increased after infection. Functionally, DDX6 augmented RIG-I mediated induction of interferon (IFN)-β expression. Notably, DDX6 was found to bind viral RNA capable to stimulate RIG-I. These findings imply a novel function for DDX6 as an RNA co-sensor and signaling enhancer for RIG-I.Peer Reviewe