Propuesta de mejora en la planta de topería de la empresa Nelana S.A.C., para mejorar la productividad de sus procesos, Arequipa 2020

El presente estudio lleva por nombre propuesta de mejora en la planta de topería de la empresa NELANA S.A.C., para mejorar la productividad de sus procesos en la ciudad de Arequipa, el cual tiene por objetivo general aplicar herramientas de ingeniería basadas en la Filosofía Lean Manufacturing e inversión en las máquinas para identificar los factores críticos que afectan la productividad y poder proponer alternativas de mejora. Se realiza el análisis situacional de la empresa NELANA S.A.C., mediante el análisis AMOFHIT, y el análisis del proceso productivo de la planta de topería mediante un trabajo de campo que permite identificar los sub procesos más críticos como el sub proceso de peinado, paralelizado y cardado entre los principales. Se identifican los principales factores que afectan la productividad, los cuales son la demora en el cambio de barretas en el sub proceso de paralelizado, la falta de señalización, orden, limpieza, demoras en el traslado del producto terminado en la zona de bolera, falta de atención de las peinadoras y cardas con la guarnición de tambor deterioradas. Las herramientas de mejora que se plantean aplicar son el VSM, la aplicación de las 5S`s en la zona de recepción, el Kanban en la salida del proceso de bolera, la aplicación del SMED en el cambio de barretas de los gill, el cambio de guarniciones en las cardas para mejorar su eficiencia. Con las herramientas de mejora propuestas se proyecta incrementar la productividad de 3.27 kg/h.h a 3,56 lo que representa un 8,86

Structure-function mapping of a heptameric module in the nuclear pore complex.

The nuclear pore complex (NPC) is a multiprotein assembly that serves as the sole mediator of nucleocytoplasmic exchange in eukaryotic cells. In this paper, we use an integrative approach to determine the structure of an essential component of the yeast NPC, the ~600-kD heptameric Nup84 complex, to a precision of ~1.5 nm. The configuration of the subunit structures was determined by satisfaction of spatial restraints derived from a diverse set of negative-stain electron microscopy and protein domain-mapping data. Phenotypic data were mapped onto the complex, allowing us to identify regions that stabilize the NPC's interaction with the nuclear envelope membrane and connect the complex to the rest of the NPC. Our data allow us to suggest how the Nup84 complex is assembled into the NPC and propose a scenario for the evolution of the Nup84 complex through a series of gene duplication and loss events. This work demonstrates that integrative approaches based on low-resolution data of sufficient quality can generate functionally informative structures at intermediate resolution

Conformational dynamics and allosteric modulation of the SARS-CoV-2 spike

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects cells through binding to angiotensin-converting enzyme 2 (ACE2). This interaction is mediated by the receptor-binding domain (RBD) of the viral spike (S) glycoprotein. Structural and dynamic data have shown that S can adopt multiple conformations, which controls the exposure of the ACE2-binding site in the RBD. Here, using single-molecule Forster resonance energy transfer (smFRET) imaging, we report the effects of ACE2 and antibody binding on the conformational dynamics of S from the Wuhan-1 strain and in the presence of the D614G mutation. We find that D614G modulates the energetics of the RBD position in a manner similar to ACE2 binding. We also find that antibodies that target diverse epitopes, including those distal to the RBD, stabilize the RBD in a position competent for ACE2 binding. Parallel solution-based binding experiments using fluorescence correlation spectroscopy (FCS) indicate antibody-mediated enhancement of ACE2 binding. These findings inform on novel strategies for therapeutic antibody cocktails

Cannabinoids activate the insulin pathway to modulate mobilization of cholesterol in C. elegans

The nematode Caenorhabditis elegans requires exogenous cholesterol to survive and its depletion leads to early developmental arrest. Thus, tight regulation of cholesterol storage and distribution within the organism is critical. Previously, we demonstrated that the endocannabinoid (eCB) 2-arachidonoylglycerol (2-AG) plays a key role in C. elegans since it modulates sterol mobilization. However, the mechanism remains unknown. Here we show that mutations in the ocr-2 and osm-9 genes, coding for transient receptors potential V (TRPV) ion channels, dramatically reduce the effect of 2-AG in cholesterol mobilization. Through genetic analysis in combination with the rescue of larval arrest induced by sterol starvation, we found that the insulin/IGF-1signaling (IIS) pathway and UNC-31/CAPS, a calcium-activated regulator of neural dense-core vesicles release, are essential for 2-AG-mediated stimulation of cholesterol mobilization. These findings indicate that 2-AG-dependent cholesterol trafficking requires the release of insulin peptides and signaling through the DAF-2 insulin receptor. These results suggest that 2-AG acts as an endogenous modulator of TRPV signal transduction to control intracellular sterol trafficking through modulation of the IGF-1 signaling pathwayFil: Hernández Cravero, Bruno. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario. Laboratorio de Fisiología Microbiana (IBR-CONICET); Argentina.Fil: Vranych, Cecilia V. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario. Laboratorio de Fisiología Microbiana (IBR-CONICET); Argentina.Fil: De Mendoza, Diego. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario. Laboratorio de Fisiología Microbiana (IBR-CONICET); Argentina.Fil: GallinoI, Sofía. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres". Laboratorio de Fisiología y Genética de la Audición (INGEBI-CONICET); Argentina.Fil: Elgoyhen, Ana Belén. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres". Laboratorio de Fisiología y Genética de la Audición (INGEBI-CONICET); Argentina.Fil: Florman, Jeremy. University of Massachusetts Medical School. Department of Neurobiology; United States.Fil: AlkemaI, Mark J. University of Massachusetts Medical School. Department of Neurobiology; United States.Fil: Diaz, Philippe. University of Montana. Department of Biomedical and Pharmaceutical Sciences; United States

Sustainability and Justice: Challenges and Opportunities for an Open STEM Education

Open educational resources, or OER, are teaching materials that reside in the public do-main and are available under an open license. While the creation of high-quality materials and cyberinfrastructure to share these resources is important, OER are much more than static resource repositories. Vibrant OER communities function as collaboration hubs and often include librarians, instructional technologists, instructors, education researchers, funders, open-source software developers, and college administrators. Together, these in-dividuals work as a community to respond to changes in the education landscape, support student learning impacts both in terms of cost savings and student retention, and solve issues related to broadly sharing open resources on the web. This essay provides general information about OER, describes communities developing OER for science, technology, engineering, and mathematics education, and presents insights about sustainability chal-lenges. The sustainability challenges are organized according to multiple dimensions: cultural and social, economic and financial, and technological and environmental. In addition, OER provide important opportunities to address and promote social justice and open and accessible education philosophies. Knowing more about the OER landscape, sustainability challenges, and educational justice opportunities can help instructors use and contribute to this growing movement to reshape the landscape of undergraduate education

Theory of hot electrons: general discussion

Sylwester Gawinkowski opened discussion of the paper by Javier Aizpurua: How many electrons are transferred by one ultrashort pulse? If you are thinking about applications in electronics, then it seems that this number may be too small. Is simply increasing the pulse energy and therefore significantly increasing the number of such emitted electrons possible

Rhesus TRIM5α disrupts the HIV-1 capsid at the inter-hexamer interfaces

TRIM proteins play important roles in the innate immune defense against retroviral infection, including human immunodeficiency virus type-1 (HIV-1). Rhesus macaque TRIM5α (TRIM5αrh) targets the HIV-1 capsid and blocks infection at an early post-entry stage, prior to reverse transcription. Studies have shown that binding of TRIM5α to the assembled capsid is essential for restriction and requires the coiled-coil and B30.2/SPRY domains, but the molecular mechanism of restriction is not fully understood. In this study, we investigated, by cryoEM combined with mutagenesis and chemical cross-linking, the direct interactions between HIV-1 capsid protein (CA) assemblies and purified TRIM5αrh containing coiled-coil and SPRY domains (CC-SPRYrh). Concentration-dependent binding of CC-SPRYrh to CA assemblies was observed, while under equivalent conditions the human protein did not bind. Importantly, CC-SPRYrh, but not its human counterpart, disrupted CA tubes in a non-random fashion, releasing fragments of protofilaments consisting of CA hexamers without dissociation into monomers. Furthermore, such structural destruction was prevented by inter-hexamer crosslinking using P207C/T216C mutant CA with disulfide bonds at the CTD-CTD trimer interface of capsid assemblies, but not by intra-hexamer crosslinking via A14C/E45C at the NTD-NTD interface. The same disruption effect by TRIM5αrh on the inter-hexamer interfaces also occurred with purified intact HIV-1 cores. These results provide insights concerning how TRIM5α disrupts the virion core and demonstrate that structural damage of the viral capsid by TRIM5α is likely one of the important components of the mechanism of TRIM5α-mediated HIV-1 restriction. © 2011 Zhao et al

HIV-1 capsid is involved in post-nuclear entry steps

BACKGROUND: HIV-1 capsid influences viral uncoating and nuclear import. Some capsid is detected in the nucleus but it is unclear if it has any function. We reported that the antibiotic Coumermycin-A1 (C-A1) inhibits HIV-1 integration and that a capsid mutation confers resistance to C-A1, suggesting that capsid might affect post-nuclear entry steps. RESULTS: Here we report that C-A1 inhibits HIV-1 integration in a capsid-dependent way. Using molecular docking, we identify an extended binding pocket delimited by two adjacent capsid monomers where C-A1 is predicted to bind. Isothermal titration calorimetry confirmed that C-A1 binds to hexameric capsid. Cyclosporine washout assays in Jurkat CD4+ T cells expressing engineered human TRIMCyp showed that C-A1 causes faster and greater escape from TRIMCyp restriction. Sub-cellular fractionation showed that small amounts of capsid accumulated in the nuclei of infected cells and C-A1 reduced the nuclear capsid. A105S and N74D capsid mutant viruses did not accumulate capsid in the nucleus, irrespective of C-A1 treatment. Depletion of Nup153, a nucleoporin located at the nuclear side of the nuclear pore that binds to HIV-1 capsid, made the virus less susceptible to TRIMCyp restriction, suggesting that Nup153 may help maintain some integrity of the viral core in the nucleus. Furthermore C-A1 increased binding of CPSF6, a nuclear protein, to capsid. CONCLUSIONS: Our results indicate that capsid is involved in post-nuclear entry steps preceding integration