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Broad-spectrum antivirals are powerful weapons against dangerous viruses where no specific therapy exists, as in the case of the ongoing SARS-CoV-2 pandemic. We discovered that a lysine- and arginine-specific supramolecular ligand (CLR01) destroys enveloped viruses, including HIV, Ebola, and Zika virus, and remodels amyloid fibrils in semen that promote viral infection. Yet, it is unknown how CLR01 exerts these two distinct therapeutic activities. Here, we delineate a novel mechanism of antiviral activity by studying the activity of tweezer variants: the "phosphate tweezer" CLR01, a "carboxylate tweezer" CLR05, and a "phosphate clip" PC. Lysine complexation inside the tweezer cavity is needed to antagonize amyloidogenesis and is only achieved by CLR01. Importantly, CLR01 and CLR05 but not PC form closed inclusion complexes with lipid head groups of viral membranes, thereby altering lipid orientation and increasing surface tension. This process disrupts viral envelopes and diminishes infectivity but leaves cellular membranes intact. Consequently, CLR01 and CLR05 display broad antiviral activity against all enveloped viruses tested, including herpesviruses, Measles virus, influenza, and SARS-CoV-2. Based on our mechanistic insights, we potentiated the antiviral, membrane-disrupting activity of CLR01 by introducing aliphatic ester arms into each phosphate group to act as lipid anchors that promote membrane targeting. The most potent ester modifications harbored unbranched C4 units, which engendered tweezers that were approximately one order of magnitude more effective than CLR01 and nontoxic. Thus, we establish the mechanistic basis of viral envelope disruption by specific tweezers and establish a new class of potential broad-spectrum antivirals with enhanced activity.

Implant loosening is a severe complication after total joint replacement. Here, differential diagnosis between septic and aseptic cases is crucial for further surgical treatment, but low-grade periprosthetic joint infections (PJIs) in particular remain a challenge. In this study, we analyzed the synovial fluid proteome of 21 patients undergoing revision surgery for septic (eight cases) or aseptic (thirteen cases) implant failure using LC-MS/MS to identify potential new biomarkers as future diagnostic tools. Staphylococci were found in four cases, Streptococci in two cases, Serratia marcescens and Cutibacterium acnes in one case. Proteomic analysis of the synovial fluid resulted in the identification of 515 different proteins based on at least two peptides. A statistical comparison revealed 37 differentially abundant proteins (p < 0.05), of which 17 proteins (46%) showed a higher abundance in the septic group. The proteins with the highest fold change included the known marker proteins c-reactive protein (7.57-fold) and the calprotectin components protein S100-A8 (4.41-fold) and protein S100-A9 (3.1-fold). However, the protein with the highest fold change was leucine-rich alpha-2-glycoprotein 1 (LRG1) (9.07-fold), a currently discussed new biomarker for inflammatory diseases. Elevated LRG1 levels could facilitate the diagnosis of PJI in the future, but their significance needs to be further investigated.

The development of three dimensional geometries by electrospinning of nonwoven, bioresorbable PDLLA nanoand microfibers is a prerequisite for multimodal growth factor delivery by biohybrids. Electrospinning of 3D tubes is a formidable task since the deposited nanofibers on the rotating mandrel adhere so strongly that newly formed tubes cannot be removed. A specific electrospinning instrument setup with a "removable mandrel sleeve" technique facilitated the reproducible synthesis of tubes for guided bone and future vascular applications. It is shown, that this technique not only allows the preparation of tubes but also of self-supported 3D rings and sandwich panels which can be functionally doped by growth factors such as rhBMP-2 to biohybrids.

Ebola (EBOV) and Zika viruses (ZIKV) are responsible for recent global health threats. As no preventive vaccines or antiviral drugs against these two re-emerging pathogens are available, we evaluated whether the molecular tweezer CLR01 may inhibit EBOV and ZIKV infection. This small molecule has previously been shown to inactivate HIV-1 and herpes viruses through a selective interaction with lipid-raft-rich regions in the viral envelope, which results in membrane disruption and loss of infectivity. We found that CLR01 indeed blocked infection of EBOV and ZIKV in a dose-dependent manner. The tweezer inhibited infection of epidemic ZIKV strains in cells derived from the anogenital tract and the central nervous system, and remained antivirally active in the presence of semen, saliva, urine and cerebrospinal fluid. Our findings show that CLR01 is a broad-spectrum inhibitor of enveloped viruses with prospects as a preventative microbicide or antiviral agent.

Adsorbate biohybrids for BMP-2 delivery based on electrospun PDLLA-nanofiber fleeces loaded with 0.6 μg/cm2 rhBMP-2COL (E. coli) strongly induced microvessel- like structures when incubated for 14 days in cocultures of human outgrowth endothelial cells (OEC) together with human primary osteoblasts (pOB). Higher loaded rhBMP-2COL biohybrids (4.6 μg/cm2) were low- to noninductive. Adsorbate biohybrids of rhBMP-2CHO (CHO cells) loaded with 1.0-6.0 μg/cm2 induced only a classic cobblestone- like growth pattern without any microvessels. Concentration- response experiments (7 days) indicate a binding affinity of rhBMP-2COL for microvessel induction in the picomolar range with nanomolar concentrations being non-inductive

Protein adsorption is the first fundamental interaction between the human body and a foreign surface. The sum of all proteins in this adherent proteinaceous layer comprises the implant proteome. The in situdental implant proteome (implantome) was eluted from four implants of two wettabilities after a 2-min dipping in the humor operationis of maxillar tooth sockets. A mean number of 2056 different polypeptides per implant were identified according to the Xcorr method (Xcorr score ≥ 1.5, n ≥ 2 peptides). In the top 12 proteins comprising ca. 47% of the total abundance, cell-free hemoglobin (26.7%) was the most abundant, followed by fibrinogen (6.4%) and serum albumin (1.8%) with additional 1,800 lower abundance polypeptides, which contained ca. 34 salivary and a similar number of autoimmunogenic polypeptides. Selective enrichment of cell-free hemoglobin on the implant vs. albumin was estimated to 270 fold

Semen is the main vector for HIV transmission and contains amyloid fibrils that enhance viral infection. Available microbicides that target viral components have proven largely ineffective in preventing sexual virus transmission. In this study, we establish that CLR01, a 'molecular tweezer' specific for lysine and arginine residues, inhibits the formation of infectivity-enhancing seminal amyloids and remodels preformed fibrils. Moreover, CLR01 abrogates semen-mediated enhancement of viral infection by preventing the formation of virion-amyloid complexes and by directly disrupting the membrane integrity of HIV and other enveloped viruses. We establish that CLR01 acts by binding to the target lysine and arginine residues rather than by a non-specific, colloidal mechanism. CLR01 counteracts both host factors that may be important for HIV transmission and the pathogen itself. These combined anti-amyloid and antiviral activities make CLR01 a promising topical microbicide for blocking infection by HIV and other sexually transmitted viruses.

Titanium implants are frequently applied to the bone in orthopedic and trauma surgery. Although these biomaterials are characterized by excellent implant survivorship and clinical outcomes, there are almost no data available on the initial protein layer binding to the implant surface in situ. This study aims to investigate the composition of the initial protein layer on endoprosthetic surfaces as a key initiating step in osseointegration. In patients qualified for total hip arthroplasty, the implants are inserted into the femoral canal, fixed and subsequently explanted after 2 and 5 min. The proteins adsorbed to the surface (the implant proteome) are analyzed by liquid chromatography–tandem mass spectrometry (LC-MS/MS). A statistical analysis of the proteins’ alteration with longer incubation times reveals a slight change in their abundance according to the Vroman effect. The pathways involved in the extracellular matrix organization of bone, sterile inflammation and the beginning of an immunogenic response governed by neutrophils are significantly enriched based on the analysis of the implant proteome. Those are generally not changed with longer incubation times. In summary, proteins relevant for osseointegration are already adsorbed within 2 min in situ. A deeper understanding of the in situ protein–implant interactions in patients may contribute to optimizing implant surfaces in orthopedic and trauma surgery.

Jak wynika z badań, Polacy na tle mieszkańców innych krajow Unii Europejskiej są uważani za naród przedsiębiorczy. W Europie więcej firm funkcjonuje tylko w tak dużych krajach, jak Hiszpania, Włochy, Niemcy, Francja czy Wielka Brytania, jednak w przeliczeniu liczby firm na 1000 mieszkańców Polska wyprzedza już Niemcy, Francję i Wielką Brytanię. Aby ta przedsiębiorczość była dobrze wykorzystana, muszą być stworzone przyjazne warunki zarówno dla prowadzących, jak i zakładających działalność gospodarczą w naszym kraju. W Zabrzu władze miejskie podjęły próbę niestandardowego rozwiązania w zakresie obsługi przedsiębiorców i osób zainteresowanych założeniem swojej firmy. W dniu 1 stycznia 2013 roku powstało, jako wydział Urzędu Miejskiego, Zabrzańskie Centrum Rozwoju Przedsiębiorczości, które m.in. zajmuje się rejestracją podmiotów prowadzących działalność gospodarczą, doradztwem, szkoleniami i edukacją młodzieży z zakresu przedsiębiorczości. Centrum podpisało partnerskie umowy z zabrzańskim Zakładem Ubezpieczeń Społecznych, Powiatowym Urzędem Pracy i Urzędem Skarbowym. Dzięki temu w mieście zostały stworzone warunki dające możliwość załatwienia w jednym miejscu, w jak najkrótszym czasie, wszystkich formalności związanych z prowadzoną działalnością oraz zarejestrowaniem nowej firmy. Działania centrum służą: podnoszeniu konkurencyjności zabrzańskiej gospodarki przez rozwój sektora MŚP, wspieraniu aktywności gospodarczej lokalnego biznesu, propagowaniu idei zakładania własnej działalności gospodarczej, wspieraniu rozwoju innowacyjnych firm. Celem niniejszego artykułu jest zapoznanie z ofertą Zabrzańskiego Centrum Rozwoju Przedsiębiorczości, ocena ponad dwuipółletniej działalności tego niestandardowego przedsięwzięcia władz samorządowych w Zabrzu oraz odpowiedzi na pytania: Jak zmieniła się obsługa przyszłych przedsiębiorców w Zabrzu? Czy działania wymienione wyżej są wystarczające, aby przedsiębiorczość Polaków mogła być wykorzystana w Polsce? Jakie przedsięwzięcia rozwijające postawy przedsiębiorcze, również wśród młodzieży, organizuje Zabrzańskie Centrum Rozwoju Przedsiębiorczości?

Semen is the main vector for HIV transmission and contains amyloid fibrils that enhance viral infection. Available microbicides that target viral components have proven largely ineffective in preventing sexual virus transmission. In this study, we establish that CLR01, a ‘molecular tweezer’ specific for lysine and arginine residues, inhibits the formation of infectivity-enhancing seminal amyloids and remodels preformed fibrils. Moreover, CLR01 abrogates semen-mediated enhancement of viral infection by preventing the formation of virion–amyloid complexes and by directly disrupting the membrane integrity of HIV and other enveloped viruses. We establish that CLR01 acts by binding to the target lysine and arginine residues rather than by a non-specific, colloidal mechanism. CLR01 counteracts both host factors that may be important for HIV transmission and the pathogen itself. These combined anti-amyloid and antiviral activities make CLR01 a promising topical microbicide for blocking infection by HIV and other sexually transmitted viruses.

It has been ten years since the business studies subject was introduced into the Core Curriculum of post-secondary schools in Poland. In 2005 and 2006 I was conducting research among students of the 2nd Upper Secondary School in Zabrze. The aim of this research was to learn about their views regarding the most important tasks of school resulting from the Core Curriculum of this subject; the most interesting information and skills acquired during the business studies and validity of introduction this subject into the post-secondary schools. Next, I will compare the results of these studies with the ones conducted this year among the present students of the 2nd Upper Secondary School, as well as with the opinions of this school’s graduates with whom I’m in contact through the social networking sites. Therefore it will be also possible to compare certain expectations of these young people with the reality of life outside the school environment.

What is globalization? What does this term mean to young people? Is the dictionary definition of th is term meaningful to them; is schoolbook information on this issue thorough and precise? What are positive results of globalization and does the youth notice any negative results of globalization in Poland and worldwide? How can they support or counteract this process? Second and third grade secondary school students were asked these and similar questions connected with globalization. As a teacher of Entrepreneurship I have always emphasized my interest in opinions and attitudes of young people. Taking into consideration the young age of the surveyed, I decided that posing questions directly connected to this year conference and teachers’ meetings title, that is entrepreneurship in the context of globalization, would be premature. I would like to present the results of the survey conducted among the students of the school I work in and their opinions on the process as well as results of globalization in this year conference sessions.

The internal market of the EU comprises an area with no internal borders, in which a free flow of persons, goods, services and capital has been introduced. Among the main aims of creating the common market were: lowering of prices and their turnover, an increase in availability and competitiveness of services and making unrestricted movement within the union possible. This was aimed to enhance living standards among citizens of member states.Polish citizens are now enjoying these freedoms. As a teacher of entrepreneurship, I am interested mainly in entrepreneurship among young people, and in this particular case, in the way they are taking advantage of the opportunities created by Poland’s accession to the EU. In order to become better acquainted with the opinions of young Poles’ on the above mentioned topics, a survey was conducted among my secondary school students. As a result, I learned about the plans of secondary school final year students concerning further education or the search for employment, including the possibility of finding work abroad. Similar research was conducted in 2006 and 2007, presenting the opportunity to compare the results. The most im­portant conclusions resulting from the comparison are the following: the students are closely following the economic situation of Poland and the EU, and are adapting their plans according to the changes currently taking place.

The development of information society has become one of the main tasks undertaken by bothnational and local authorities as well as by institutions responsible for the development of entrepreneurship. Relevant projects are financed by the European Union. Prime Minister DonaldTusk mentioned this subject in his expose and emphasized the importance of knowledge andinformation society in the economic development of Poland. For us, teachers, it is important to know how can we help to increase the entrepreneurshipof young people, and encourage them and provide with opportunities to use moderntechnologies. Information technology in the education should not be limited to IT classes inthe computer lab. The Internet resources can be used for all classes, especially entrepreneurshipclasses. More attention should be paid to skills essential when our students looking for a joband when they decide to start their own businesses. This paper comprises reflections on implementation of information technology in the task of developing the youth’s entrepreneurshipand an attempt on answering the question from the title.

Striving to completely explain the concept of entrepreneurship we have to look into the workof three fields of science: economics, sociology and psychology. Among the skills and qualitiesnecessary for an entrepreneur they name the following: readiness and ability to make decisions,creative approach to problem solving, courage, creativity, resourcefulness, persistence and wil-lingness to work. Therefore the teachers of entrepreneurship have to pass on to their studentsspecific knowledge and skills useful for their participation in social and economic life, as wellas encourage certain qualities and attitudes concerned with taking advantage of opportunitiesand openness to novelty under all circumstances, not necessarily as an entrepreneur. Choosingthe teaching methods, it is worth to get to know the opinions and expectations of your studentsconcerning the skills they consider important and necessary on the Polish job market. I havebeen looking into this issue with final year students for several years. It turns out that the pre-ferences of young people who are getting ready to enter the job market are changing and te-achers should react to this fact. One of the latest tendencies is to put more emphasis on gettingskills and later knowledge. Furthermore, students realize that even when they possess knowledge,they should also have the ability to make use of it.

This paper tries to show an image and define qualities vital to a modern entrepreneur. The requirements for entrepreneurs are very high. An entrepreneur must be both a founder and organizer, as well as manager and leader. In order to play these roles well one should possess certain qualities and abilities. It is necessary to have so called „spirit of enterprising”, to be creative and innovative, which will let us find a niche on the market and prosper in the competitive world. Furthermore, it is vital to be able to manage the personnel and time - an important resource in our times. Also, we should be able to interpret and use the accessible information and our knowledge that should be constantly broadened. It is important to have the sense of responsibility, as there is no enterprise without financial and legal risk. Above list shows that this set of qualities and abilities is hard to develop. The teachers’ task, who give Introduction to Enterprising lesson, is to show young people what qualities are necessary for a modern entrepreneur, and what to do in order to develop them. Today’s students should decide on the shape of tomorrow economy in Poland.

Young people are becoming more and more active on the labour market these days. Thenumber of young adults who are studying and working at the same time is increasing. Thesestatements are confirmed by research done all over Poland and the survey conducted among the last year students of The Second Comprehensive School in Zabrze. Young people acquire their first job experience during their education, after completing grammar school course. They treat their careers very seriously in a planned and unhurried manner. They are conscious of the necessity of further education, especially mastering foreign languages and getting more skills and experience. A national research and my own survey come to theconclusion that young people seem to be performing better and better on the labour market andbecoming, in compliance with our intentions, more and more entrepreneurial.