A artrose, também chamada de osteoartrose ou osteoartrite (OA), é a terceira doença de maior incidência no Mundo. Nesse trabalho, buscou-se criar uma lesão osteocartilaginosa em joelhos de ratos Wistar machos com seis meses de vida, objetivando constituir um modelo animal para estudo da OA humana e, a partir desse modelo, avaliar biomateriais de forma isolada ou associados entre si e avaliados quanto à sua segurança biológica e potencial de reparação tecidual. Além disto, foi analisado o efeito reparador de células-tronco mesenquimais da polpa do dente de leite humano (MSC) isoladamente e em associação com o biomaterial formado por: Titânio + Poli Vinil Álcool + Ac. Hialurônico, nesse estudo denominado de TRIGEL (TRG). O Ac. Hialurônico (HA), por suas propriedades visco elásticas, o pó de Titânio (Ti), devido às suas propriedades biológicas únicas de ostoeintegração e o polímero Poli Vinil Álcool (PVA), com suas propriedades hidrofílicas, promovendo a formação do Hidrogel, os quais associados entre si formam um compósito, o TRG, que foi aplicado sobre uma lesão padrão no joelho da pata pélvica direita de ratos Wistar machos de seis meses de idade. Para a obtenção da lesão padrão, os animais foram divididos em três grupos de cincoanimais e cada grupo foi submetido a uma intervenção cirúrgica em seus joelhos direitos, utilizando três técnicas cirúrgicas diferentes, a saber: Grupo (I): Remoção cirúrgica dos meniscos medial e lateral mais perfuração do platô tibial seguido da aspiração da medula óssea através dessa perfuração por meio de seringa e agulha. Grupo (II): Remoção dos meniscos mais perfuração, sem aspiração, Grupo (III): Apenas a perfuração. Todos os animais foram autopsiados após 30 dias. Os joelhos dos quinze animais que constituíam os três grupos foram devidamente catalogados e enviados para a empresa Histotech, para a confecção das lâminas, tendo sido eleito, por análise histológica, o Grupo (I), por demonstrar menor reparo tecidual espontâneo. Em tese, o TRG teria as seguintes propriedades: Uma fonte de reparação tecidual (visco terapia) dada pelo HA e a capacidade amortecedora e carreadora de células-tronco do polímero PVA, que se hidrata, formando o hidrogel. O Ti, pela sua propriedade de osteointegração formaria um tampão sobre as áreas de matriz óssea exposta o que possibilitaria o afluxo de novos condrócitos, que também pode ocorrer pela ação das células-tronco. Livrar a superfície articular das áreas com exposição da matriz óssea é fundamental para o bloqueio das proteases que perpetuam a fisiopatologia da OA. Após tratamento estatístico dos diversos ensaios, utilizando-se os diversos biomateriais no tratamento da lesão, o TRG foi o biomaterial que apresentou o melhor resultado de força entre os grupos. No estudo histológico, foi evidenciada a presença de tecido cartilaginoso supra- lesional, o que só ocorreu nos animais dos grupos que receberam: apenas TRG, TRG associado com células-tronco e aquele que recebeu apenas MSCs. No entanto, mais estudos, com animais de maior porte e mais velhos, devem ser realizados para melhor analisar a segurança e o potencial terapêutico do compósito Trigel. / Osteoarthritis, or osteoarthritis (OA) is the third most debilitating disease in the world. In this study, we attempted to create an osteocartilaginous lesion in the knees of six months old male Wistar rats, aiming to constitute an animal model for the study of human OA and to use this model to evaluate the therapeutic potential of biomaterials, which are already well known for their biocompatibility properties in the clinical practice. The biomaterials were used in isolation or associated with each other and then evaluated for their biological safety and tissue repair capacity. Mesenchymal stem cells, obtained from human dental pulp from deciduous teeth (MSC) were evaluated alone and in association with the biomaterial formed by: Titanium + Poly Vinyl Alcohol + Ac. Hyaluronic, here called TRIGEL (TRG). Due to its visco-elastic properties, the Ti powder, due to its unique biological properties of ostointegration and the polymer PVA, with its hydrophylic properties, forming a hydrogel, were associated to form the composite named TRIGEL, (TRG), which was applied to a standard knee injury of the right hind leg of male Wistar rats. In order to elect the standard lesion, the animals were divided into three groups with five animals each and each group underwent a surgical intervention in their right knees, with three different surgical techniques being applied, namely: Group (1): Surgical removal ofmedial and lateral meniscus plus perforation of the tibial plateau, followed by aspiration of the bone marrow through this perforation using syringe and needle. Group (2): Removal of the meniscus plus perforation, without aspiration, Group (3): Drilling only. All groups were autopsied 30 days after the procedure and all groups were autopsied at 30 days post-procedure. The knees of the 15 animals that constituted the three groups were analyzed histologically and Group (1) (meniscus removed, perforated and aspirated), was elected as the standard lesion since it demonstrated less spontaneous tissue repair. TRG has the following properties: HA is used as a source of tissue repair (visco therapy) and hydration of the polymer; PVA, forms a hydrogel\", with damping action and as a stem cells carrier, whereas Ti was used due to its ósseo-integration, which would allow coating of the exposed bone matrix and this intra-osseous osteo-integration response would form an intercalating buffer. The healthy cartilage surfaces around this structural buffer would allow the reception of new chondrocytes or the action of the cells on TRG properties. Freeing the articular surface of the areas with bone matrix exposure is critical for blocking the proteases that perpetuate the pathophysiology of OA. In the various biomaterial tests in the treatment of the standard lesions, TRG was statistically shown to be the one that better mimicked the non-injured group. The histological study demonstrated the presence of a supra-lesional cartilagenous tissue, which only occurred in the groups which received: only TRG, mesenchymal stem cells associated with TRG and that which received only MSCs. However, further studies with larger and older animals should be pursued to better assess the safety and therapeutic potential of the Trigel composite.

A artrose, também chamada de osteoartrose ou osteoartrite (OA), é a terceira doença de maior incidência no Mundo. Nesse trabalho, buscou-se criar uma lesão osteocartilaginosa em joelhos de ratos Wistar machos com seis meses de vida, objetivando constituir um modelo animal para estudo da OA humana e, a partir desse modelo, avaliar biomateriais de forma isolada ou associados entre si e avaliados quanto à sua segurança biológica e potencial de reparação tecidual. Além disto, foi analisado o efeito reparador de células-tronco mesenquimais da polpa do dente de leite humano (MSC) isoladamente e em associação com o biomaterial formado por: Titânio + Poli Vinil Álcool + Ac. Hialurônico, nesse estudo denominado de TRIGEL (TRG). O Ac. Hialurônico (HA), por suas propriedades visco elásticas, o pó de Titânio (Ti), devido às suas propriedades biológicas únicas de ostoeintegração e o polímero Poli Vinil Álcool (PVA), com suas propriedades hidrofílicas, promovendo a formação do Hidrogel, os quais associados entre si formam um compósito, o TRG, que foi aplicado sobre uma lesão padrão no joelho da pata pélvica direita de ratos Wistar machos de seis meses de idade. Para a obtenção da lesão padrão, os animais foram divididos em três grupos de cincoanimais e cada grupo foi submetido a uma intervenção cirúrgica em seus joelhos direitos, utilizando três técnicas cirúrgicas diferentes, a saber: Grupo (I): Remoção cirúrgica dos meniscos medial e lateral mais perfuração do platô tibial seguido da aspiração da medula óssea através dessa perfuração por meio de seringa e agulha. Grupo (II): Remoção dos meniscos mais perfuração, sem aspiração, Grupo (III): Apenas a perfuração. Todos os animais foram autopsiados após 30 dias. Os joelhos dos quinze animais que constituíam os três grupos foram devidamente catalogados e enviados para a empresa Histotech, para a confecção das lâminas, tendo sido eleito, por análise histológica, o Grupo (I), por demonstrar menor reparo tecidual espontâneo. Em tese, o TRG teria as seguintes propriedades: Uma fonte de reparação tecidual (visco terapia) dada pelo HA e a capacidade amortecedora e carreadora de células-tronco do polímero PVA, que se hidrata, formando o hidrogel. O Ti, pela sua propriedade de osteointegração formaria um tampão sobre as áreas de matriz óssea exposta o que possibilitaria o afluxo de novos condrócitos, que também pode ocorrer pela ação das células-tronco. Livrar a superfície articular das áreas com exposição da matriz óssea é fundamental para o bloqueio das proteases que perpetuam a fisiopatologia da OA. Após tratamento estatístico dos diversos ensaios, utilizando-se os diversos biomateriais no tratamento da lesão, o TRG foi o biomaterial que apresentou o melhor resultado de força entre os grupos. No estudo histológico, foi evidenciada a presença de tecido cartilaginoso supra- lesional, o que só ocorreu nos animais dos grupos que receberam: apenas TRG, TRG associado com células-tronco e aquele que recebeu apenas MSCs. No entanto, mais estudos, com animais de maior porte e mais velhos, devem ser realizados para melhor analisar a segurança e o potencial terapêutico do compósito Trigel. / Osteoarthritis, or osteoarthritis (OA) is the third most debilitating disease in the world. In this study, we attempted to create an osteocartilaginous lesion in the knees of six months old male Wistar rats, aiming to constitute an animal model for the study of human OA and to use this model to evaluate the therapeutic potential of biomaterials, which are already well known for their biocompatibility properties in the clinical practice. The biomaterials were used in isolation or associated with each other and then evaluated for their biological safety and tissue repair capacity. Mesenchymal stem cells, obtained from human dental pulp from deciduous teeth (MSC) were evaluated alone and in association with the biomaterial formed by: Titanium + Poly Vinyl Alcohol + Ac. Hyaluronic, here called TRIGEL (TRG). Due to its visco-elastic properties, the Ti powder, due to its unique biological properties of ostointegration and the polymer PVA, with its hydrophylic properties, forming a hydrogel, were associated to form the composite named TRIGEL, (TRG), which was applied to a standard knee injury of the right hind leg of male Wistar rats. In order to elect the standard lesion, the animals were divided into three groups with five animals each and each group underwent a surgical intervention in their right knees, with three different surgical techniques being applied, namely: Group (1): Surgical removal ofmedial and lateral meniscus plus perforation of the tibial plateau, followed by aspiration of the bone marrow through this perforation using syringe and needle. Group (2): Removal of the meniscus plus perforation, without aspiration, Group (3): Drilling only. All groups were autopsied 30 days after the procedure and all groups were autopsied at 30 days post-procedure. The knees of the 15 animals that constituted the three groups were analyzed histologically and Group (1) (meniscus removed, perforated and aspirated), was elected as the standard lesion since it demonstrated less spontaneous tissue repair. TRG has the following properties: HA is used as a source of tissue repair (visco therapy) and hydration of the polymer; PVA, forms a hydrogel\", with damping action and as a stem cells carrier, whereas Ti was used due to its ósseo-integration, which would allow coating of the exposed bone matrix and this intra-osseous osteo-integration response would form an intercalating buffer. The healthy cartilage surfaces around this structural buffer would allow the reception of new chondrocytes or the action of the cells on TRG properties. Freeing the articular surface of the areas with bone matrix exposure is critical for blocking the proteases that perpetuate the pathophysiology of OA. In the various biomaterial tests in the treatment of the standard lesions, TRG was statistically shown to be the one that better mimicked the non-injured group. The histological study demonstrated the presence of a supra-lesional cartilagenous tissue, which only occurred in the groups which received: only TRG, mesenchymal stem cells associated with TRG and that which received only MSCs. However, further studies with larger and older animals should be pursued to better assess the safety and therapeutic potential of the Trigel composite.

Köln, Universiẗat, Diss., 2007.

My thesis serves two purposes: First, my research addresses what I have come to recognize as colonial misunderstandings of nuu-chah-nulth ha'wiih. My research and writing invoke new ways of thinking about nuu-chah-nulth people, leaders and knowledge. I accomplish this by writing conversationally and by including unedited interviews and poetry. All of which require readers to consider my research outside of their usual perspective. Second, my research responds to a cultural need to archive important family knowledge while providing the opportunity to define, for outsiders, who we are. The interviews archive, in part, the knowledge and teachings of a cha-cha-tsi-us-aht ha'wilth. My analysis of this information shows that while my family’s knowledge comes from a common source. We all interpret that knowledge in our own way. My research is important academically and politically because of its ability to convey knowledge that has not been simplified, appropriated or colonized for public consumption.

The assignment of the diploma thesis was the elaboration of an architectural study of a new synagogue in the town of Trutnov, on the site of the original Jewish synagogue, which was burned down during the November pogrom, the so-called Crystal Night in 1938. Nowadays, the synagogue area is modified and serves as a place of reverence to honour the memory of the victims and to commemorate these historical events. The result of the design is a new community centre. Its goal is to restore the existence and support the development of the Jewish community, which disappeared in Trutnov after the Second World War. In the area there is the seat of the Jewish community, a ritual cleansing bath Mikveh, Kosher restaurant and a new synagogue, which respects the location of the former synagogue on the site of the original foundations. The new Jewish community centre ensures the operation of the entire Jewish community in Trutnov. Part of the Jewish community centre is a large courtyard, which is used to celebrate Jewish holidays and also as a summer terrace for Kosher restaurant, which will be used by the Jewish community, but also by the inhabitants of Trutnov. This creates an attractive place to spend free time with a view of the nearby Giant Mountains and the historic centre of Trutnov, but at the same time it is protected from the bustle of the adjacent main street.

The thesis aims to examine and refine the concepts of flesh and spirit in Musar le-Mevin, discussing Jörg Frey's hypothesis of the possibility to derive Paul's concept of sarx from Palestinian sapiential literature, in light of recent advancements in the field. The first part of the thesis is dedicated to the term baśar and its relationship to sin, knowledge and election. The second part focuses on the term jeṣer, its possible translation and the role it might have played in the development of the concept of jeṣer ha-raʿ as an evil agent. The third part analyses the term ruaḥ and describes how the sapiential composition develops its specific view of the spirit. The last chapter attempts to locate the text in relation to other intertestamental views of flesh and sin. Finally, the thesis discusses the possibility of studying Musar le-Mevin as a background to Paul's anthropology. The thesis suggests that the text develops an idea of allotted shares of the spirit which determine a person's position and fate. It also attempts to describe how this view incorporates ruaḥ baśar as a designation for those who were not given the knowledge of good and evil. The term baśar might be understood as the outcome of a fusion of the traditional Biblical connotations of fleetingness and earthliness with a pessimistic...

Hyaluronan (HA) is a substance that is commonly used in biomedical applications in the form of hydrogels. One of these biomedical applications is dermatological fillers where HA is cross-linked with 1,4-Butanediol diglycidyl ether (BDDE) to reduce its rapid turnover within tissue. The filler gives a volumetric effect that can fill out wrinkles. This literature study was conducted in collaboration with Galderma to determine if there is research that explores additives to HA hydrogels that give both volumetric and biological effects when applied as filler. Biological effects that improve the skin's appearance and complexion such as a rejuvenation of the skin was preferable. Both polynucleotides and mannitol show great potential to act as additives in injectable hyaluronan hydrogels.  The main effect of polynucleotides (PN) added in hydrogels is that it is collagen stimulating and provides a more natural tissue regeneration. Rheological properties of the filler change with the addition of PN, where elasticity, viscosity and viscoelasticity have been shown to increase. PNs show no toxicity and are considered safe to inject. The study of mannitol has shown that it does not give a volumetric effect after the injected hydrogel has been broken down. What mannitol can help with, is to prolong the life of the hydrogel and reduce the swelling that is a common side effect after an injection. In addition to this, mannitol is a safe substance to inject.

Depuis leur expulsion de la Terre sainte après la destruction du Second Temple (70 C.E.), les Juifs ne cessèrent d'espérer y retourner. Au fil des siècles, se développèrent plusieurs mouvements d'immigration (l'ʼaliyāh) motivés souvent par des aspirations millénaires. Les plus marquants sont ceux de Tossaphistes de France et d'Angleterre durant le XIIIème siècle, et par la suite de Juifs d'Espagne qui immigrèrent en Terre sainte après l'expulsion de 1492. En 1700, Rabbi Juda ha-Ḥasid (1660-1700) organisa une ʼaliyāh collective en provenance d'Europe de l'Est, dirigée vers Jérusalem. Plus tard, à partir de 1760 se formèrent plusieurs mouvements d' ʼaliyāh tant de disciples de Rabbi Israel Baal Shem Tov (1690-1760) - les ḥasidim, que ceux de Rabbi Eliyahu- le Gaon de Vilna (1720-1797)- les pĕrūšīm. La première partie de cette étude analyse les motivations de ces mouvements, et met en lumière la doctrine rédemptrice du Gaon de Vilna à travers une recherche originale de sa biographie et de ses ouvrages novateurs. Dans sa deuxième partie, elle analyse comment les disciples du Gaon mirent en pratique en Terre sainte les enseignements de leur maître. Afin de saisir la portée de leurs actions, il est nécessaire de comprendre le contexte géopolitique de l'Empire ottoman et de la Palestine du début du XIXème siècle, ainsi que la particularité des Capitulations régissant le statut des étrangers. Cette étude montre comment les pĕrūšīm surent agir de façon efficace et très innovante face aux problèmes majeurs de l'implantation juive en Terre d’Israël, notamment en ce qui concerne les relations avec le pouvoir ottoman local et avec les représentants des Puissances et les consuls européens, le développement économique et la création d'un système scolaire nouveau. / Since their expulsion from the Holy Land after the destruction of the Second Temple (70 C.E.), the Jews did not cease to hope to return. Over the centuries, immigration movements (Aliyot) grew, often motivated by millennia aspirations. The most notable are those of the Tossafists of France and England during the 13th century, and later, the Jews of Spain who immigrated to the Holy Land after the expulsion of 1492. In 1700, Rabbi Judah ha-Hasid (1660-1700) organized a collective Aliyah from Eastern Europe to Jerusalem. Later, from 1760, several Aliyah movements emerged such as the immigration of the disciples of Rabbi Israel Baal Shem Tov (1690-1760), known as the Hasidim, and of the disciples of Rabbi Eliahu, the Vilna Gaon (1720-1797), known as the Perushim. The first part of this study analyzes the motivations of these movements, and highlights the redemptive doctrine of the Vilna Gaon through original research on his biography and his innovative works. In its second part, the study analyzes how the Gaon's disciples put the teachings of their master into practice in the Holy land. To grasp the significance of their actions, it is necessary to understand the geopolitical context of the Ottoman Empire and Palestine from the early 19th century, and the particularity of the "Capitulations" governing the status of foreigners. This study shows how the Perushim knew how to act effectively and very innovatively concerning the major challenges which the Yishuv, the Jewish settlement, faced. Among the areas of activity in which the disciples of the Gaon involved themselves were the relations with the ottoman local government and with representatives of the Powers, economic development and the creation of a unique educational system.

This project is a Bachelor’s thesis conducted by two students at KTH Royal Institute of Technology. The report aims to assess the implementation of sustainable agriculture at the farm Rosenhill, in the Stockholm region in Sweden, and provide potential agroecological solutions. The assessment of the farm functioned as a case study to explore possible ways to improve sustainable practices in agriculture. The method used for assessing agricultural practices in this thesis was drawn from the existing methods IDEA and complemented with the intent to find agroecological approaches. The data gathering was conducted through interviews and observations at the farm, as well as receiving complementing documents from the farm. The data from the interviews and observation was then compiled into a document and divided up into categories, corresponding to the indicators chosen for the analysis. Each individual indicator was first examined individually and, on this ground, concluding comments on the overall implementation of sustainable agriculture were drawn. Results show that the farm is implementing sustainable agriculture the ectively, however, areas of improvement were also identied. The following agroecological practices were further discussed as potential solutions to problems identied at the farm: Intercropping and/or Companion Planting, Cover-cropping and Reduced Tillage, and Agroforestry. / De a projekt är en kandidatexamensarbete skriven av två studenter på Kungliga Tekniska Högskolan (KTH). Rapporten har som syfte att bedöma implementeringen av hållbart jorbruk på odlingen Rosenhill, i Stockholmsregionen, och ge potentiella agroekologiska lösningar. Bedömningen av odlingen fungerade som en fallstudie för att utforska möjliga sätt att förbättra hållbara tillämpningar inom jordbruk. Metoden som användes i detta arbete för att bedöma tillämpningen av jordbruk hämtades från de existerande metoderna IDEA och RISE och komplementerad med avsikten a hitta agroekologiska angreppssätt. Insamlingen av data gjordes genom intervjuer och observationer, samt dokument från odlingen. Data från intervjuer och observationer sattes samman i ett dokument och delades in i kategorier, motsvarande indikatorer valda för analys. Varje individuell indikator analyserades enskilt först och baserat på detta drogs det avslutande kommentarer på den övergripande implementeringen av hållbart jordbruk. Resultaten visar att odlingen implementerar hållbart jordbruk väl, dock kunde förbättringsområden identifieras. Följande tillämpningar av agroekologi diskuterades som potentiella lösningar till problem som identifierades på odlingen: Samodling av lämpliga grödor, Täckningsgrödor och reducerad jordbearbetning och Skogsjordbruk.

Influenza A Viren (IAV) infizieren die Epithelzellen unserer Atemwege und stellen ein weltweites Gesundheitsproblem dar. Die Infektion beginnt mit der Bindung an Sialinsäure (SA) auf der Wirtszelloberfläche. Zwischen einem SA-Molekül und dem viralen Oberflächenprotein Hämagglutinin (HA) kommt es dabei zur Interaktion durch nicht kovalente Bindung. Die Inhibierung dieses entscheidenden Schrittes des Infektionszyklus durch Präsentation eines kompetitiven Binders ist ein möglicher Ansatz für ein antiviral wirkendes Mittel. Das Prinzip, mit dem IAV an Zellen binden, ist die Multivalenz. Detailliertes Wissen zur Multivalenz, speziell zur HA-SA-Interaktion, ist für eine effektive IAV-Inhibition von Nöten. Diese Arbeit untersucht und charakterisiert die HA-SA-Interaktion auf zwei unterschiedlichen Wegen. Wird SA auf einer ausgewählten Gerüststruktur funktionalisiert, kann es zu einer multivalenten Anordnung des IAV-Rezeptors kommen. Derartige multivalente Nanopartikel (NP) wurden in Bindungsstudien hinsichtlich ihres Potenzials charakterisiert IAV effektiv zu binden und zu inhibieren. Die Effektivität und die damit einhergehende Stabilität der HA-SA-Interaktionen der getesteten NP, die auf drei verschiedenen Gerüststrukturen basieren (Coiled-Coil-Peptid, PNA-DNA-Strang, Polyglycerolkomplex), hängt von der Verteilung elektrostatischer Oberflächenladungen und der Flexibilität der Gerüststruktur ab. Im zweiten Teil der Arbeit wurden Veränderungen auf Seiten des HAs analysiert. Zwei IAV mit Mutationen in der HA-Bindetasche, sowie das Wildtypvirus wurden in Messungen mittels Einzel-Virus-Kraft-Spektroskopie hinsichtlich ihres Bindungsverhaltens an SA charakterisiert. Die Daten belegen, dass die Verteilung elektrostatischer Oberflächenladungen im HA Einfluss auf die HA-SA-Interkation hat. Alle Ergebnisse zusammengenommen liefern neue Erkenntnisse über die Einflussnahme der HA-SA-Interaktion und wie daraus abgeleitet multivalente Nanopartikel weiter optimiert werden können. / The Influenza A virus (IAV) infects epithelial cells of the human respiratory tract and represents a global health problem. Every infection starts with virus binding on sialic acid (SA) displayed on the host cell surface. This step is characterized by interaction between the viral surface protein hemagglutinin (HA) and sialic acid (SA) that leads to a non-covalent binding. Inhibition of this crucial step of viral infection cycle by presenting a competitive binder to IAV is one approach utilized during the design of antiviral compounds. IAV binds specifically to cells by using the principle of multivalency. Targeting an effective virus inhibition requires detailed knowledge about the binding mechanism, especially about the HA-SA-interaction. This work focuses on the evaluation and characterization of the HA-SA-interaction following two different approaches. In case SA is functionalized on an appropriate scaffold structure, the IAV receptor can arrange in a multivalent fashion. These multivalent nanoparticles (NP) have been studied regarding their potential to effectively bind and inhibit IAV. This potential is directly linked to the stability of the HA-SA-interactions of the tested NPs, which are based on three different scaffold structures (coiled-coil peptide, PNA-DNA-strand, a complex of polyglycerols) and depends on the distribution of electrostatic surface charges and the flexibility of the scaffold structure. The second part of this thesis analyzed changes at HA. The wildtype virus and two IAVs comprising each a mutation in the binding pocket of HA were characterized regarding their binding behavior by single-virus-force-spectroscopy. Results revealed that the arrangement of electrostatic surface charges on HA affecting the HA-SA-interaction. Taken together, all results provide new and important insights into the dependence of the HA-SA-interaction and how this knowledge can be used to further optimize multivalent NPs.