No description available.

No description available.

No description available.

Relatively little is known about the vesicular stomatitis virus (VSV) glycoprotein G fusion mechanism. Vesicular stomatitis virus has a single type 1 integral membrane glycoprotein G embedded in the viral membrane. It is the only viral protein required for VSV induced low pH mediated fusion. Mutations in four regions (H2, A5, A4 and HI0) of the VSV G ectodomain have been shown to abolish the fusion activity of the viral glycoprotein (Li et al.,l993). One region H2 (a.a 117-139) has been suggested to be the fusion peptide (Zhang and Ghosh, 1994)(Fredericksen and Whitt, 1995). Amino acids 59-221 of the G protein, an area that encompasses the H2 region, has recently been shown to interact with liposomes through hydrophobic photolabeling experiments (Durrer et al., 1995), suggesting that the H2 region (fusion peptide)is able to interact with hydrophobic target bilayers at low pH. A soluble VSV G protein lacking the transmembrane anchor and cytoplasmic tail of VSV G is not fusogenic, suggesting that G must be anchored to the plasma membrane to promote syncytia (Florkiewicz and Rose, 1984). To better understand the steps involved in the fusion mechanism of VSV G it is important to identify domains within the protein that are involved in the fusion process. To determine the contributions of the transmembrane anchor and cytoplasmic tail to the VSV fusion mechanism chimeric G proteins were constructed. The transmembrane anchor alone or in conjunction with the cytoplasmic tail ofVSV G was replaced with equivalent domain from other viral proteins, HSV-1 glycoproteins gB and gD, adenovirus E3 11.6 K gene, that are not involved in low-pH fusion and the cellular protein CD4. All chimeras were expressed in COS-1 cells, glycosylated, oligomerized, transported to the cdl surface, showed a low-pH induced conformational change and were expressed on the cell surface at levels equivalent to wild-type G. The transmembrane hybrids show extensive syncytia formation at levels similar to wild-type G when induced at pH 5.6. The transmembrane-cytoplasmic tail hybrids showed reduced levels of syncytia as compared to wild-type Gat both pH 5.6 and 5.2. A glycosylphosphatidylinositollipid-anchored ectodomain of G (GGPI), which lacks both the transmembrane and cytoplasmic tail ofG, was expressed in COS-1 cells. The GGPI chimera was glycosylated, expressed on the cell surface,and oligomerized similar to wild-type G. However the chimera was fusion negative, could not promote lipid mixing and h~,d an altered tryptic digestion profile. A fusion negative chimera Gt12gBwas constructed by exchanging the TM of G with the equivalent domain from HSV-1 gB TM plus eight extra amino acids of the gB ectodomain. Deletion of the 11 extra gB amino acids (GgB3G) restored the fusogenic activity of this chimera. Another chimera G 10 DAF directly demonstrated that the fusion negative phenotype of GGPI, like chimera Gtii1Lll2gB, was a result of the 10 extra amino acids at the EC-TM interface. The ectodomain (EC)-transmembrane (TM) interface is highly conserved among 5 vesiculoviruses. Chimeras with a 9 amino acid insertion (GlODAF), deletion (G~9) or replacement (G~910DAF) were expressed in COS-1 cells. The expressed proteins were glycosylated, underwent a low-pH induced conformational change and were expressed on the cell surface at levels equivalent to wild type, but were fusion negative. Suggesting that both the sequence and spatial arrangement of amino acids at the EC-TM interface may affect VSV G fusion. Taken together the data suggests that the specific amino acid sequence of the transmembrane anchor of VSV G is not essential for fusion. Replacement of the TM of VSV G with equivalent domains from other viral and cellular proteins does not affect the fusion activity. The cytoplasmic tail of VSV G may form an entity alone or in conjunction with the transmembrane anchor that can regulate fusion. Another region in the ectodomain of VSV G renders the glycoprotein fusion sensitive in a cell-cell fusion assay and was characterized at the EC-TM interface. / Thesis / Master of Science (MS)

Various forms of staking, guying, and root ball anchoring are used to prevent post-transplant tree destabilization in the landscape, but little scientific evidence exists to support this practice. This experiment tested the efficacy of three generic tree stabilization systems (TSS) and their effect on tree growth and establishment. In spring 2006, 48 balled and burlapped, 6.4 cm (2.5 inch) diameter, white ash (Fraxinus americana L. Autumn Purpleâ ) were transplanted to a field site in Blacksburg, VA. At planting, one of four TSS treatments (staking, guying, root ball anchoring, or non-stabilized) was installed on each tree. After five weeks, tree pulling tests were conducted on 24 trees to simulate a strong wind load using a cable winch mounted to a skid-steer loader. After one growing season, change in tree height, trunk diameter, and trunk taper were compared among the 24 remaining trees. Soil cores were taken and the length, diameter, and dry weight of roots within the cores were analyzed. TSS were then removed and tree pulling tests were conducted using the same method. The five week tests showed that destabilization was significantly greater for non-stabilized trees (mean of 16 degrees from vertical) than for trees with TSS (all means less than 3 degrees from vertical). Yet after one growing season, there were no significant differences among any treatments in tree stability. We conclude that in locations with high wind speeds, TSS may be necessary for trees similar to those in our study, but only for a very short period of time. Results also indicated that staking, guying, and root ball anchoring were equally effective, very robust, very durable, caused no tree injuries, and did not impact tree growth or establishment after one growing season. Practical considerations may therefore play a more important role when choosing which TSS to use. Although the time required for TSS installation was similar for each system, staking was more than twice as expensive as guying or root ball anchoring. / Master of Science

Cancer immunotherapy has long been proposed as a powerful approach to curing tumors, based on the natural function of the immune system in protecting its host with specificity, thus holding the potential for developing long-term memory that prevents tumor recurrence. However, the immunosuppressive feature of the tumor microenvironment prevents the patients' own immune system from functioning normally in the fight against cancer. As one of the most potent cancer immunotherapies, immunostimulatory cytokines have been shown to elicit anti-tumor immune responses in preclinical studies, but their clinical application is limited by severe immune-related adverse events upon systemic administration. None of the current delivery strategies can fully address issues of toxicities and sustainably supply cytokines over the course of a few days without compromising cytokines' structural integrity. Herein, we have developed a novel formulation to anchor potent cytokine molecules to the surface of large-sized particles (1 µm) for local cancer treatment. The cytokines are confined in tumors and have minimal systemic exposure over a few days following intratumoral injection, thereby eliciting anti-tumor immunity while avoiding the systemic toxicities caused by the circulating cytokines. Such particle-anchored cytokines can be synergistic with other immunotherapies, including immune checkpoint blockade antibodies and tumor antigens, to safely promote tumor regressions in various syngeneic tumor models and genetically engineered murine tumor models. / Doctor of Philosophy / Cancer immunotherapy is a promising method to treat cancer by harnessing the power of the body's immune system, which naturally fights off diseases and can remember and prevent diseases from returning. Unfortunately, cancers create a hostile environment that weakens the immune system's ability to combat the disease effectively. Among the treatments explored, immunostimulatory cytokines (unique proteins that boost the immune system) have shown great promise in laboratory studies for their ability to fight cancer. However, when these proteins are administered to patients, they can cause severe side effects due to their systemic dissemination throughout the body. Herein, by attaching the potent cytokines to large-sized particles (1 µm), and injecting them directly into the tumor, their cancer-fighting abilities are focused precisely where they are most needed. This targeted delivery minimizes the cytokines' presence in the rest of the body, dramatically reducing the risk of side effects associated with their systemic dissemination. This method not only shows promise on its own but also enhances the effectiveness of other cancer treatments. Our findings suggest a new, safer way to encourage the body's defense system to fight cancer more effectively.

De par leur nature scientifique, les sciences économiques visent, entre autre, à observer, qualifier, ainsi que quantifier des phénomènes économiques afin de pouvoir en dégager diverses prévisions. Ce mémoire se penche sur ces prévisions et, plus particulièrement, sur les facteurs pouvant biaiser les prévisionnistes au niveau comportemental en référant à l’effet d’ancrage, un biais propre à l’économie comportementale – une sous-discipline des sciences économiques. Il sera donc question de comprendre, par une analyse selon la discipline que représente l’économie comportementale, ce qui peut les affecter, avec un accent mis sur l’effet d’ancrage plus précisément. L’idée générale de ce dernier est qu’un agent peut être biaisé inconsciemment par la simple connaissance d’une valeur précédente lorsqu’il est demandé de faire une estimation ultérieure. De cette façon, une analyse des salaires des joueurs de la Ligne Nationale de Hockey (NHL) selon leurs performances passées et leurs caractéristiques personnelles, de 2007 à 2016, a été réalisée dans ce travail afin d’en dégager de possibles effets d’ancrage. Il est alors possible de constater que les directeurs généraux des équipes de la ligue agissent généralement de façon sensible et rationnelle lorsque vient le temps d’octroyer des contrats à des joueurs mais, néanmoins, une anomalie persiste lorsqu’on porte attention au rang auquel un joueur a été repêché. Dans un tel contexte, il semble pertinent de se référer à l’économie comportementale afin d’expliquer pourquoi le rang au repêchage reste une variable significative huit ans après l’entrée d’un joueur dans la NHL et qu’elle se comporte à l’inverse de ce que prévoit la théorie à ce sujet. / Economic analysis, by its nature, involves observing, qualifying and quantifying economic data with the ultimate goal of making forecasts. In this masters thesis, I am interested in factors that could bias a forecaster's behavior – with special focus on phenomena, like the anchoring effect, that have been proposed in behavioral economics. At a fundamental level, the anchoring effect states that an agent's ability to accurately forecast may be affected by placing unwarranted emphasis on certain economic variables. To study this effect, I analyze how the salaries of National Hockey League (NHL) players are determined by the players' characteristics and past performance. From the results, it would appear that NHL general managers are generally sensible and rational when it comes to using historical data to make decisions about player salaries. However, there is a persistent anomaly regarding the draft position of a player. Although one would not expect the draft position to be very important after eight years of experience in the NHL, the analysis shows that it is remains a significant determinant of player salary. Behavioral economics and more specifically, the anchoring effect, helps explain why this might be so.

An abstract knowledge representation of cognitive robots - as used for reasoning and planning - typically relies on symbols denoting objects of the world and states of affairs. The process of creating and maintaining the correct connection between a symbol denoting an object and its corresponding perceptual image (called percept), both referring to the same physical object, is called symbol anchoring. Most current cognitive systems implement an ad hoc solution which may work for the specific, intended application under certain conditions. Conversely, we suggest a formal and general approach to the symbol anchoring problem, which enhances previous approaches in terms of flexibility, applicability and expressiveness, and which completely automates the process of determining and maintaining all plausible hypotheses of correspondences between object symbols and perceptual images of physical objects. Based on the first-order logical Fluent Calculus, our approach inherits its rich expressiveness with respect to knowledge representation and reasoning. Implementing all required symbol anchoring functionalities, our approach also complies with fundamental concepts of phenomenalism, representationalism and the sense-data theory of philosophy of cognition.

An abstract knowledge representation of cognitive robots - as used for reasoning and planning - typically relies on symbols denoting objects of the world and states of affairs. The process of creating and maintaining the correct connection between a symbol denoting an object and its corresponding perceptual image (called percept), both referring to the same physical object, is called symbol anchoring. Most current cognitive systems implement an ad hoc solution which may work for the specific, intended application under certain conditions. Conversely, we suggest a formal and general approach to the symbol anchoring problem, which enhances previous approaches in terms of flexibility, applicability and expressiveness, and which completely automates the process of determining and maintaining all plausible hypotheses of correspondences between object symbols and perceptual images of physical objects. Based on the first-order logical Fluent Calculus, our approach inherits its rich expressiveness with respect to knowledge representation and reasoning. Implementing all required symbol anchoring functionalities, our approach also complies with fundamental concepts of phenomenalism, representationalism and the sense-data theory of philosophy of cognition.

Syfte: Denna uppsats behandlar en undermedveten kognitiv bias vilken benämns som ”anchoring effect” eller förankringseffekten. Effekten uppenbaras då människor tenderar att lägga för mycket tillit till den första informationen som görs tillgänglig vid olika typer av beslutsfattande. Teoriramen för detta forskningsområde är tämligen utbredd med drygt 40 år av studier som på senare tid börjat undersöka förankringseffektens påverkan vid förhandlingar. Dessutom finns utbredda konstateranden för att betydande kunskap inte lindrar effekten i någon större omfattning. Däremot föreligger bristande forskningsslutsatser kring hur kunskapsvarians vid förhandlingar  påverkar förankringseffekten. Till följd av detta avser studien att undersöka nedanstående syfte: Syftet med denna studie är att undersöka hur förankringseffekten påverkar utfallet i en förhandlingssituation, när kunskapsvarians råder mellan parterna gällande det aktuella förhandlingsområdet. Metod: I studien genomfördes ett experiment med totalt 44 deltaganden. Experimenten utgjordes av prisförhandlingar gällande en fiktiv bostad, där varje enskild deltagare fick genomgå två förhandlingar vardera. Den första förhandlingen avsåg en lägenhetsförsäljning och den andra en villaförsäljning där parterna agerade säljare respektive köpare. I experimentgruppen förelåg det kunskapsvarians då tredjeårsstudenter från fastighetsmäklarprogrammet mötte studenter med annan utbildningsbakgrund. I kontrollgruppen ställdes motsatsvis deltagare från samma utbildning mot varandra för att skapa mindre skillnader i kunskap beträffande det aktuella förhandlingsområdet. Resultat & slutsats: Resultatet i denna studie tyder på att deltagare vars kunskap stod dem till förfogande, alstrat förmånligare överenskommelser i jämförelse med deltagare med låg kunskapsnivå. Detta trots att deltagarna vars kunskapsnivå var låg, erhållit fördelen av förankringseffekten då de fick lägga det första budet. Resultatet indikerar därmed att förankringseffekten kan lindras till följd av kunskapsvarians vid förhandlingar. Förslag till vidare forskning: Vidare forskning bör utgå från liknande förhandlingsexperiment där forskaren i första hand eftersträvar att generera större kunskapsskillnader mellan parterna i förhandlingen. En större omfattning av denna studie torde således resultera i ökade statistiska klarheter vilket torde vara gynnsamt för det aktuella forskningsområdet. Uppsatsens bidrag: Studiens bidrag är att forskningsresultaten tyder på en lindring av förankringseffekten vid kunskapsvarians inom förhandlingar. Detta till skillnad från tidigare studier där olika kunskapnivåer inte visats ha någon större betydelse. I och med att ingen tidigare studie undersökt detta förhållande har denna studie lyckats identifiera ett tydligt forskningsgap som bidragits till. / Aim: This paper is about a subconscious cognitive bias referred to as "Anchoring Effect". The effect is revealed by the fact that people tend to put too much trust in the first information that is made available in different types of decision-making situations. The theory framework for this research area is fairly widespread with over 40 years of studies, and lately the research has begun examining the anchoring effect in different types of negotiation dyads. In addition, there are widespread findings that significant knowledge does not mitigate the effect in any notable degree. However, there is a lack of research findings regarding how differences in knowledge within negotiations might affect the anchoring effect. Therefore, this study intends to investigate the following: The purpose of this study is to investigate how the anchoring effect is affecting the outcome of a negotiation, when the parties have different levels of knowledge regarding the negotiated area. Method: This study has conducted an experiment with a total of 44 participants. The experiments have involved simulated price negotiations regarding a condominium and a residence property. Each participant performed two negotiations each, one for respective dwelling place. In the experimental group, there was a difference in knowledge when third year students from a real estate brokering program negotiated with students from other programs. In contradistinction to the experimental group, the control group included students with similar education background in order to create minor knowledge differences within the negotiated area. Result & Conclusion: The result of this study shows undeniably that the experiment participants with greater knowledge have generated more favourable agreements, compared to the participants with lower relevant knowledge. Even though the participants with lower knowledge had the advantage of presenting the initial offer in the experimental group. Thus, a mitigation of the anchoring effect has been identified as a result of differences in knowledge within the negotiations. Further research: Further research should be based on similar negotiation experiments with focus on creating greater differences in knowledge between the participants. This in combination with a larger replica of our study should enable increased statistical clarities with fruitful outcomes in this research field. Contribution of the thesis: The theoretical contribution of our study is primarily the fact that the anchoring effect tends to be mitigated by variance in knowledge within negotiations. Considering that no previous studies have examined this before, we argue that a clear research gap have been identified and that our findings has contributed to the theoretical framework.