In vitro differentiation of near-unlimited numbers of functional mouse basophils using conditional Hoxb8

Background: Basophils constitute a rare leukocyte population known for their effector functions in inflammation and allergy, as well as more recently described immunoregulatory roles. Besides their low frequency, functional analysis of basophils is hindered by a short life span, inefficient ex vivo differentiation protocols, and lack of suitable cell models. A method to produce large quantities of basophils in vitro would facilitate basophil research and constitute a sought-after tool for diagnostic and drug testing purposes. Methods: A method is described to massively expand bone marrow–derived basophils in vitro. Myeloid progenitors are conditionally immortalized using Hoxb8 in the presence of interleukin-3 (IL-3) and outgrowing cell lines selected for their potential to differentiate into basophils upon shutdown of Hoxb8 expression. Results: IL-3-dependent, conditional Hoxb8-immortalized progenitor cell lines can be expanded and maintained in culture for prolonged periods. Upon shutdown of Hoxb8 expression, near-unlimited numbers of mature functional basophils can be differentiated in vitro within six days. The cells are end-differentiated and short-lived and express basophil-specific surface markers and proteases. Upon IgE- as well as C5a-mediated activation, differentiated basophils release granule enzymes and histamine and secrete Th2-type cytokines (IL-4, IL-13) and leukotriene C4. IL-3-deprivation induces apoptosis correlating with upregulation of the BH3-only proteins BCL-2-interacting mediator of cell death (BIM) and p53 upregulated modulator of apoptosis (PUMA) and downregulation of proviral integration site for Moloney murine leukemia virus 1 kinase (PIM-1). Conclusion: A novel method is presented to generate quantitative amounts of mouse basophils in vitro, which moreover allows genetic manipulation of conditionally immortalized progenitors. This approach may represent a useful alternative method to isolating primary basophils.

Is there a ‚Depth versus Participation‘ Dilemma in International Cooperation?

Much of the International Relations literature assumes that there is a “depth versus participation” dilemma in international politics: shallower international agreements attract more countries and greater depth is associated with less participation. We argue that this conjecture is too simple and probably misleading because the depth of any given cooperative effort is in fact multidimensional. This multidimensionality manifests itself in the design characteristics of international agreements: in particular, the specificity of obligations, monitoring and enforcement mechanisms, dispute settlement mechanisms, positive incentives (assistance), and organizational structures (secretariats). We theorize that the first three of these design characteristics have negative and the latter three have positive effects on participation in international cooperative efforts. Our empirical testing of these claims relies on a dataset that covers more than 200 global environmental treaties. We find a participation-limiting effect for the specificity of obligations, but not for monitoring and enforcement. In contrast, we observe that assistance provisions in treaties have a significant and substantial positive effect on participation. Similarly, dispute settlement mechanisms tend to promote treaty participation. The main implication of our study is that countries do not appear to stay away from agreements with monitoring and enforcement provisions, but that the inclusion of positive incentives and dispute settlement mechanisms can promote international cooperation. In other words, our findings suggest that policymakers do not necessarily need to water down global treaties in order to obtain more participation.

Expectation Conditional Maximization-Based Deformable Shape Registration

This paper addresses the issue of matching statistical and non-rigid shapes, and introduces an Expectation Conditional Maximization-based deformable shape registration (ECM-DSR) algorithm. Similar to previous works, we cast the statistical and non-rigid shape registration problem into a missing data framework and handle the unknown correspondences with Gaussian Mixture Models (GMM). The registration problem is then solved by fitting the GMM centroids to the data. But unlike previous works where equal isotropic covariances are used, our new algorithm uses heteroscedastic covariances whose values are iteratively estimated from the data. A previously introduced virtual observation concept is adopted here to simplify the estimation of the registration parameters. Based on this concept, we derive closed-form solutions to estimate parameters for statistical or non-rigid shape registrations in each iteration. Our experiments conducted on synthesized and real data demonstrate that the ECM-DSR algorithm has various advantages over existing algorithms.

Reputation Formation and the Evolution of Cooperation in Anonymous Online Markets

Theoretical propositions stressing the importance of trust, reciprocity, and reputation for cooperation in social exchange relations are deeply rooted in classical sociological thought. Today’s online markets provide a unique opportunity to test these theories using unobtrusive data. Our study investigates the mechanisms promoting cooperation in an online-auction market where most transactions can be conceived as one-time-only exchanges. We first give a systematic account of the theoretical arguments explaining the process of cooperative transactions. Then, using a large dataset comprising 14,627 mobile phone auctions and 339,517 DVD auctions, we test key hypotheses about the effects of traders’ reputations on auction outcomes and traders’ motives for leaving feedback. Our statistical analyses show that sellers with better reputations have higher sales and obtain higher prices. Furthermore, we observe a high rate of participation in the feedback system, which is largely consistent with strong reciprocity—a predisposition to unconditionally reward (or punish) one’s interaction partner’s cooperation (or defection)—and altruism—a predisposition to increase one’s own utility by elevating an interaction partner’s utility. Our study demonstrates how strong reciprocity and altruism can mitigate the free-rider problem in the feedback system to create reputational incentives for mutually beneficial online trade.

Academic cooperation to foster research and advocacy competences in the occupied Palestinian territory (West Bank)

Palestinians living in the West Bank, a territory occupied by the State of Israel according to International Law, face deprived access to land and a limited ability to move freely which pertains to the presence of Israeli settlements and other infrastructure (closures, restricted or forbidden roads, etc.). This confinement has significant impacts on their economic and social livelihoods, and it is even worsening with the on-going construction of a 709 km long Barrier which mainly runs inside the West Bank. With regard to this situation, there is a clear need to strengthen the capacity of civil society and its representatives to apply sound research processes as a basis for improved advocacy for Palestinian human rights. Monitoring processes and tools are needed to assess the impacts of the Palestinians’ confinement, particularly in relation to the Barrier’s construction. Reliable data has also to be collected, managed, and above all, shared. These challenges have been addressed within the Academic Cooperation Palestine Project (ACPP) that brings together academic partners from the occupied Palestinian territory (oPt) West Bank (WB), and Switzerland as well as other international academic institutions and Palestinian governmental and non-governmental agencies. ACPP started in early 2011 and is designed as a large cooperation networking platform involving researchers, students, public servants and experts from the oPt WB. A large set of actions have already been developed during the first year of the project, including courses, training, and research actions. First relevant results and impacts of the different actions are presented in this paper. Taken as a whole, the project produces valuable results for all partners: useful advocacy material for the Palestinian partners, and a unique “real-scale laboratory” where investigations are jointly conducted to develop novel confinement and change indicators.