Near Infrared Fluorescent Nanoparticles Derived from Hyaluronic Acid Improve Tumor Contrast for Image-Guided Surgery.

Tumor tissue that remains undetected at the primary surgical site can cause tumor recurrence, repeat surgery, and treatment strategy alterations that impose a significant patient and healthcare burden. Intraoperative near infrared fluorescence (NIRF) imaging is one potential method to identify remaining tumor by visualization of NIR fluorophores that are preferentially localized to the tumor. This requires development of fluorophores that consistently identify tumor tissue in different patients and tumor types. In this study we examined a panel of NIRF contrast agents consisting of polymeric nanoparticle (NP) formulations derived from hyaluronic acid (HA), with either physically entrapped indocyanine green (ICG) or covalently conjugated Cy7.5. Using orthotopic human breast cancer MDA-MB-231 xenografts in nude mice we identified two lead formulations. One, NanoICGPBA, with physicochemically entrapped ICG, showed 2.3-fold greater tumor contrast than ICG alone at 24 h (p \u3c 0.01), and another, NanoCy7.5100-H, with covalently conjugated Cy7.5, showed 74-fold greater tumor contrast than Cy7.5 alone at 24 h (p \u3c 0.0001). These two lead formulations were then tested in immune competent BALB/c mice bearing orthotopic 4T1 breast cancer tumors. NanoICGPBA showed 2.2-fold greater contrast than ICG alone (p \u3c 0.0001), and NanoCy7.5100-H showed 14.8-fold greater contrast than Cy7.5 alone (p \u3c 0.0001). Furthermore, both NanoICGPBA and NanoCy7.5100-H provided strong tumor enhancement using image-guided surgery in mice bearing 4T1 tumors. These studies demonstrate the efficacy of a panel of HA-derived NPs in delineating tumors in vivo, and identifies promising formulations that can be used for future in vivo tumor removal efficacy studies

Rpn11-mediated ubiquitin processing in an ancestral archaeal ubiquitination system

While protein ubiquitination was long believed to be a truly eukaryotic feature, recently sequenced genomes revealed complete ubiquitin (Ub) modification operons in archaea. Here, we present the structural and mechanistic characterization of an archaeal Rpn11 deubiquitinase from Caldiarchaeum subterraneum, CsRpn11, and its role in the processing of CsUb precursor and ubiquitinated proteins. CsRpn11 activity is affected by the catalytic metal ion type, small molecule inhibitors, sequence characteristics at the cleavage site, and the folding state of CsUb-conjugated proteins. Comparison of CsRpn11 and CsRpn11-CsUb crystal structures reveals a crucial conformational switch in the CsRpn11 Ins-1 site, which positions CsUb for catalysis. The presence of this transition in a primordial soluble Rpn11 thus predates the evolution of eukaryotic Rpn11 immobilized in the proteasomal lid. Complementing phylogenetic studies, which designate CsRpn11 and CsUb as close homologs of the respective eukaryotic proteins, our results provide experimental support for an archaeal origin of protein ubiquitination

Methodology for planning production processes with the use of decision tables in the metal industry

The study was conducted in a manufacturing company. The publication discusses the methodology for designing the production process using decision tables. The purpose of this article is to draw attention to the use of decision tables in production design. Production, as the main link that adds value to manufacturing companies, is the most important process within the organization. The ability to make decisions, in terms of the production process, is related to the development of the enterprise or lack thereof. Help is needed in making decisions, which should have the best effect on the functioning of the whole company and generate the highest profits. Decisions at the production stage are crucial to the operations of the whole company

Bus Rapid Transit : modern transportation solution

W artykule zaprezentowano system Bus Rapid Transit (BRT), innowacyjne rozwiązanie transportowe, wdrażane w nielicznych aglomeracjach miejskich. Scharakteryzowano przykłady rozwiązań BRT na świecie. Zidentyfikowano kluczowe wskaźniki w zakresie BRT. Wdrożenie BRT połączone jest z osiąganiem istotnych korzyści, do których należą: szybkość realizacji inwestycji na etapie projektowania i wykonawstwa, w porównaniu z innymi rodzajami transportu, stosunkowo niskie koszty inwestycji i koszty eksploatacji, a także możliwość połączenia z już istniejącą siecią drogową, co wykazano w publikacji.The article presents the Bus Rapid Transit System. It’s an innovative transport solution, implemented in many urban aglomerations. BRT solutions in the world have been characterized. Key BRT indicators have been identified

Analysis of IT solutions used in the planning process of urban transport

Profesjonalne firmy transportowe na co dzień stają przed różnymi wyzwaniami, począwszy od zwiększania liczby pasażerów, poprawy jakości usług, aż do zmniejszenia kosztów operacyjnych i obsługi pojazdów. W celu osiągnięcia założonych celów, przysparzających sukces w tej dziedzinie, niezbędne jest wdrożenie efektywnego oprogramowania systemowego do sporządzania rozkładów jazdy. W artykule zostały przedstawione wybrane rozwiązania informatyczne prezentowane przez firmy zajmujące się projektowaniem rozkładów jazdy w miastach dla przedsiębiorstw świadczących usługi transportu zbiorowego.Professional transport companies are facing a variety of challenges each day, from increasing passenger numbers, improving service quality, and reducing operating costs and handling costs. In order to achieve successful targets in this area, it is necessary to implement effective system software for scheduling. The article presents selected IT solutions presented by companies dealing with the design of urban timetables for companies providing public transport services

Analysis of definitions in agile supply chains

W artykule dokonano charakterystyki zwinnych łańcuchów dostaw wraz z analizą zakłóceń. Postępująca globalizacja w zasadniczy sposób wpływa na zarządzanie przedsiębiorstwami oraz na przepływ towarów i usług. Jedną z założeń w przepływie towarów jest koncepcja zwinnego łańcucha dostaw. Aby efektywnie zarządzać łańcuchami dostaw oraz utrzymać odpowiednią pozycję na rynku, konieczne jest zdefiniowanie ewentualnych zakłóceń. Artykuł przedstawia możliwe do występowania zakłócenia w tradycyjnych modelach łańcucha dostaw oraz z wyszczególnieniem zakłóceń w zwinnych systemach zarządzania.The article discusses the characteristics of agile supply chains with disturbance analysis. One of the assumptions in the flow of goods is the concept of agile supply chain. In order to effectively manage supply chains and maintain an appropriate market position, it is necessary to define possible interruptions. This article presents possible interference in traditional supply chain models and specifies interference in agile management systems

Implementation of lean 5s methodology in logistic enterprise

The Japanese 5S method is the basis for optimizing processes in the enterprises. An example of the practices in the logistics enterprise is presented. These practices are an important prerequisite for successful work in the enterprise and have a positive impact on the implementation of the 5S system and other methods. 5S contributes to the development of the learning organization with employees. 5S practise is one of the techniques to improve quality and safety and health at the workplace. It was first popularized by Taiichi Ohno, who designed the Toyota Production System and Shigeo Shingo, who also put forward the concept of poka-yoke. The article presents Lean 5S methodology and selected results of research on performance and interference, before and after implementation of the 5S method in the logistic enterprise. The purpose of this paper is to implement the 5S and principles to assist manufacturing organisations to become more efficient and more productive. The case study presented in the paper will be useful to researchers, professionals and others concerned with this subject to understand the significance of 5S and Lean