Enhancing anticancer cytotoxicity through bimodal drug delivery from ultrasmall Zr MOF nanoparticles

Dual delivery of dichloroacetate and 5-fluorouracil from Zr MOFs into cancer cells is found to enhance in vitro cytotoxicity. Tuning particle size and, more significantly, surface chemistry, further improves cytotoxicity by promoting caveolae-mediated endocytosis and cytosolic cargo delivery

EVALUATION INFORMATION SYSTEM DELIVERY PT. RST CARGO INTERNATIONAL

The purpose of this study was to evaluate the application of general controls and application controls on the sale of information systems as a basis to support and produce accurate information in decision-making. The research methodology used was the literature research, field research consisting of interviews and observations, questionnaires, analysis and auditing method that I use is Auditing Around the Computer. The research literature sourced from reference books, interviews conducted by asking questions to the audit, the observation is done by making a list of questions intended for the use of the system and the analysis is done by analyzing the findings of the evaluation and identifying the strengths and weaknesses of internal control. From this analysis, the findings obtained advantages and disadvantages of internal control. Weaknesses are found to be expressed in the form of finding problems, risks and recommendations as a follow- improvement. Conclusions derived from the results of the evaluation for management control and operational security in information systems delivery PT. RST International Cargo are still some shortcomings , while in applications such as boundary control, input and output can meet and support the delivery of PT. RST Cargo Internationa

Lysosomal Delivery of Bioactive Proteins to Living Human Cells via Engineered Exosomes

Exosomes are naturally secreted nanovesicles derived from mammalian cells that are used for intercellular communication in vivo. As a result, they can potentially be used for intracellular delivery of therapeutics for disease treatment. We have developed an exosome pseudotyping approach using vesicular stomatitis virus glycoprotein (VSVG) to produce protein chimeras that optimize production of modified exosomes containing protein therapeutics and facilitate effective delivery to their target cells. To the VSVG transmembrane scaffold, we have fused both fluorescent and luminescent reporters for exosome tracking/visualization and quantification of activity respectively. Through our design, we have shown the biogenesis of VSVG modified exosomes from transfected producer cells through fluorescence imaging and the production of a VSVG-based stable cell line. In addition, we have characterized isolated engineered exosomes and shown that they exhibited the correct size, distribution, and molecular markers, while retaining the bioactivity of their protein cargo. Furthermore, we show that our engineered exosomes and their protein cargo are internalized by multiple cell lines into the endosomal and lysosomal compartments of those cells. Lastly, these modified exosomes can confer their bioactive cargo, either a luminescent reporter or puromycin resistance into these target cells. In summary, this study presents a novel approach to exosome engineering to enhance therapeutic protein loading and delivery, and more importantly, shows the delivery of modified exosomes to intracellular lysosomal compartments. This aspect leads to the assumption that in future studies, these engineered exosomes can be used as a vehicle for delivery of therapeutic proteins for treatment of lysosomal storage diseases

Breaking free:endocytosis and endosomal escape of extracellular vesicles

Extracellular vesicles (EVs) are natural micro-/nanoparticles that play an important role in intercellular communication. They are secreted by producer/donor cells and subsequent uptake by recipient/acceptor cells may result in phenotypic changes in these cells due to the delivery of cargo molecules, including lipids, RNA, and proteins. The process of endocytosis is widely described as the main mechanism responsible for cellular uptake of EVs, with endosomal escape of cargo molecules being a necessity for the functional delivery of EV cargo. Equivalent to synthetic micro-/nanoparticles, the properties of EVs, such as size and composition, together with environmental factors such as temperature, pH, and extracellular fluid composition, codetermine the interactions of EVs with cells, from binding to uptake, intracellular trafficking, and cargo release. Innovative assays for detection and quantification of the different steps in the EV formation and EV-mediated cargo delivery process have provided valuable insight into the biogenesis and cellular processing of EVs and their cargo, revealing the occurrence of EV recycling and degradation, next to functional cargo delivery, with the back fusion of the EV with the endosomal membrane standing out as a common cargo release pathway. In view of the significant potential for developing EVs as drug delivery systems, this review discusses the interaction of EVs with biological membranes en route to cargo delivery, highlighting the reported techniques for studying EV internalization and intracellular trafficking, EV-membrane fusion, endosomal permeabilization, and cargo delivery, including functional delivery of RNA cargo.</p

SPS program review transportation perspective

The delivery of cargo and space workers to the SPS construction site requires the development of two different systems, one to handle large cargo deliveries and a smaller system to accommodate crew. The overall scenario of the transportation system is shown. Eight major elements comprise the transportation system: personnel launch vehicle (PLV) or shuttle; personnel orbital transfer vehicle (POTV); the heavy lift launch vehicle (HLLV); the electric orbital transfer vehicle (EOTV); intra orbit transfer vehicle (IOTV); LEO support facility; GEO support facility and a shuttle derived HLLV (SDHLLV) for supporting the early SPS Demonstration Program. The HLLV and EOTV represent the cargo carriers while the PLV and POTV represent the people carriers. The IOTV is utilized to ferry people and cargo modules over short distances in the vicinity of its station

Cellular mechanisms for cargo delivery and polarity maintenance at different polar domains in plant cells

The asymmetric localization of proteins in the plasma membrane domains of eukaryotic cells is a fundamental manifestation of cell polarity that is central to multicellular organization and developmental patterning. In plants, the mechanisms underlying the polar localization of cargo proteins are still largely unknown and appear to be fundamentally distinct from those operating in mammals. Here, we present a systematic, quantitative comparative analysis of the polar delivery and subcellular localization of proteins that characterize distinct polar plasma membrane domains in plant cells. The combination of microscopic analyses and computational modeling revealed a mechanistic framework common to diverse polar cargos and underlying the establishment and maintenance of apical, basal, and lateral polar domains in plant cells. This mechanism depends on the polar secretion, constitutive endocytic recycling, and restricted lateral diffusion of cargos within the plasma membrane. Moreover, our observations suggest that polar cargo distribution involves the individual protein potential to form clusters within the plasma membrane and interact with the extracellular matrix. Our observations provide insights into the shared cellular mechanisms of polar cargo delivery and polarity maintenance in plant cells

MAPping out distribution routes for kinesin couriers

In the crowded environment of eukaryotic cells, diffusion is an inefficient distribution mechanism for cellular components. Long-distance active transport is required and is performed by molecular motors including kinesins. Furthermore, in highly polarized, compartmentalized and plastic cells such as neurons, regulatory mechanisms are required to ensure appropriate spatio-temporal delivery of neuronal components. The kinesin machinery has diversified into a large number of kinesin motor proteins as well as adaptor proteins that are associated with subsets of cargo. However, many mechanisms contribute to the correct delivery of these cargos to their target domains. One mechanism is through motor recognition of subdomain-specific microtubule (MT) tracks, sign-posted by different tubulin isoforms, tubulin post-translational modifications (PTMs), tubulin GTPase activity and MT associated proteins (MAPs). With neurons as a model system, a critical review of these regulatory mechanisms is presented here, with particular focus on the emerging contribution of compartmentalised MAPs. Overall, we conclude that – especially for axonal cargo – alterations to the MT track can influence transport, although in vivo, it is likely that multiple track-based effects act synergistically to ensure accurate cargo distribution

Perbaikan Kinerja Penanganan Kargo Ikan Tuna; di Terminal Kargo Bandar Udara Internasional Soekarno Hatta

The objectives of this study were 1) to identify the tuna cargo handling conducted in the export warehouse of PT. XYZ, 2) to determine the main variables that affect the performance of tuna cargo handling in the export warehouse of PT. XYZ, and 3) to determine what policies can be used to improve the performance of tuna cargo handling in the export warehouse of PT. XYZ. This research was conducted by using the descriptive methodology i.e. a discrete simulation model of the process of tuna cargo handling in the export warehouse of PT. XYZ by utilizing ARENA software. In the policy making of tuna cargo handling improvements, the Analytical Network Process, Benefit, Opportunity, Cost, and Risk (ANP BOCR) were also used. The simulation results point out that the existing conditions contribute to the delay level of tuna cargo delivery by 12% with the quality level of 22,934%. Delays in tuna cargo delivery have led to an increase in operational costs by 1,5%. ANP BOCR results highlight that opening a special lane for perishable cargo handling will improve the performance of tuna cargo handling in the export warehouse of PT. XYZ. Furthermore, the results of discrete model simulations on the improvement scenario of tuna cargo handling performance show that by opening a special lane for perishable cargo handling, it can ensure delivery schedule to be accurate indicated by the level of on time delivery reaching up to 100%, with an average quality rate of 86.013%. By speeding up the processing period (with an average of 81.519 minutes), the delay of cargo delivery up to 100% will be reduced; therefore, the quality of tuna is maintained in a good condition with the histamine level of 6,7 ppm

Passive Optical Sample Assembly (POSA) for STS-1 quick look post-mission report

A passively deployed array of contamination-sensitive samples was mounted and flown in the cargo bay of the space shuttle Columbia during the first orbital flight test. A similar unit was mounted in a different location in the cargo bay at Dryden Flight Research Center during the postflight operations there prior to the ferry flight return of Columbia to Kennedy Space Center. The samples in both POSA arrays were subjected to a series of optical and analytical measurements prior to delivery for installation in the cargo bay and after retrieval of the flight hardware. A quick-look summary of the results of a comparison of the series of measurements is presented