Strategic Payments in Financial Networks

In their seminal work on systemic risk in financial markets, Eisenberg and Noe [Larry Eisenberg and Thomas Noe, 2001] proposed and studied a model with n firms embedded into a network of debt relations. We analyze this model from a game-theoretic point of view. Every firm is a rational agent in a directed graph that has an incentive to allocate payments in order to clear as much of its debt as possible. Each edge is weighted and describes a liability between the firms. We consider several variants of the game that differ in the permissible payment strategies. We study the existence and computational complexity of pure Nash and strong equilibria, and we provide bounds on the (strong) prices of anarchy and stability for a natural notion of social welfare. Our results highlight the power of financial regulation - if payments of insolvent firms can be centrally assigned, a socially optimal strong equilibrium can be found in polynomial time. In contrast, worst-case strong equilibria can be a factor of ?(n) away from optimal, and, in general, computing a best response is an NP-hard problem. For less permissible sets of strategies, we show that pure equilibria might not exist, and deciding their existence as well as computing them if they exist constitute NP-hard problems

Multiple glycerol shocks increase the calcium phosphate transfection of non-synchronized CHO cells

The exposure of CHO DG44 cells to an osmotic shock, after DNA uptake, results in a cellular volume decrease of approx. 55%. Repetitive osmotic shocks targeted different sub-populations of cells as was demonstrated using two different fluorescent reporter genes. Also the exposure of a calcium phosphate-DNA coprecipitate to high osmolarity in vitro caused the release of the DNA from the precipitate. The results demonstrate the importance of the osmotic shock on the efficient delivery of plasmid DNA to the nucleus of CHO cells following calcium phosphate-mediated transfectio

Ovarian dysfunction associated with zona pellucida-based immunocontraceptive vaccines

Despite more than 40 years of research into zona pellucida (ZP)-based vaccines, relatively little is known about their mechanism of action. Early research demonstrated precipitation of ZP glycoproteins by antiovarian antiserum, rendering oocytes resistant to sperm binding in vitro. Subsequent work showed significantly decreased fertilization rates following passive immunization, sparking interest in anti-ZP immunocontraception for human and animal use. The primary mechanism of action of ZP vaccines is generally considered to be an antibody-mediated interference with sperm-oocyte binding and/or fertilization. However, this mechanism of action excludes the potential for ovarian dysfunction associated with anti-ZP treatment in some species. A review of relevant literature in pertinent model, domestic and wildlife species reveals a variety of previous and current hypotheses for ovarian effects following ZP-based immunization. Ovarian dysfunction has been suggested to be a species-specific response. In addition, cytotoxic T-lymphocytes and the use of Freund's adjuvants have been suggested to play a role. Finally, the type and extent of glycosylation of ZP antigens have been proposed to influence ovarian effects. The validity of these hypotheses is re-examined in the light of current knowledge. Further investigation of ovarian function in species believed to be resistant to the ovarian effects of anti-ZP vaccines is warranted. To this end, anti-Milllerian hormone may provide a novel tool for the assessment of ovarian function during ZP-based immunocontraception, particularly in wildlife species not amenable to frequent clinical examination

The Kinetics of Polyethylenimine-Mediated Transfection in Suspension Cultures of Chinese Hamster Ovary Cells

The kinetics of polyethylenimine (PEI)-mediated gene transfer at early times after transfection of Chinese hamster ovary (CHO) cell in suspension were investigated using a novel in vitro assay. Addition of an excess of competitor DNA to the culture medium at various times after the initiation of transfection inhibited further cellular uptake of PEI-DNA particles. Using this approach, a constant rate of particle uptake was observed during the first 60min of transfection at a PEI:DNA ratio of 2:1 (w/w) and a cell density of 2×106cells/ml under serum-free conditions. The uptake rate declined considerably during the next 2h of transfection. Both the rate and the level of PEI-DNA uptake in serum-free minimal medium were found to be dependent on the PEI-DNA ratio, the cell density at the time of transfection, and the extent of particle aggregation. These studies of the early phase of PEI-mediated transfection are expected to lead to further opportunities for optimization of gene transfer to suspension cultures of mammalian cells for the purpose of large-scale transient recombinant protein productio

Ovarian function in pony mares undergoing porcine zona pellucida immunocontraception

An advantage of the porcine zona pellucida (pZP) vaccine over other immunocontraceptives is the preservation of reproductive cyclicity and associated behaviors. Few studies have investigated ovarian function following pZP vaccination in the mare despite reported ovarian dysfunction in other species. The objectives of this study were to investigate ovarian function and estrous cyclicity in pony mares during immunocontraception with the conventional pZP vaccine. Fourteen mares were randomized into two groups of seven. Group I received 100 µg of pZP with Freund’s complete modified adjuvant (FCMA; V1), followed after five weeks by booster vaccination with 100 µg of pZP with Freund’s incomplete adjuvant (FIA; V2). Group II (controls) received two treatments five weeks apart of saline with FCMA (V1) and saline with FIA (V2) respectively. Treatments were administered via intramuscular injection into the gluteal muscles. Data were collected by an investigator blinded to treatment group over a period of 24 weeks during the physiological breeding season. All mares underwent estrus monitoring via trans-rectal palpation and ultrasound examination of the internal reproductive tract, on D0 (day of ovulation), D7, and D14 of consecutive estrous cycles, with daily monitoring between D14 and D0 of the following cycle. Artificial insemination was performed using fresh semen for up to two consecutive estrous cycles, commencing five weeks post-V2. Serum samples were collected weekly for the analysis of antibody titres and ovarian steroid (progesterone and estradiol) levels. Data were compared using Mann-Whitney U tests using commercially available software (IBM SPSS Statistics Version 22, International Business Machines Corp., Armonk, NY). Statistical significance was set as P < 0.05. All Group II mares showed normal estrous cyclicity throughout the study. Four Group I mares showed signs of anestrus within seven weeks of V2, characterised by small, inactive ovaries and baseline progesterone and estradiol levels. One Group I mare entered anestrus within 11 weeks of V2 and a second showed estrus with ovulation between variable periods of anestrus. Ovarian volumes, follicle counts and maximal follicle diameters in Group I were significantly lower than Group II. Per-cycle pregnancy proportions in Groups I and II were 0% and 78% respectively. This study demonstrated suppression of ovarian function in six of seven (86%) mares following pZP immunocontraception. Further research into the mechanism of action of zona pellucida-based vaccines is warranted

Researching immunocontraceptive vaccines with mares (Equus caballus) as both a target and model for African elephant (Loxodonta africana) cows: a review

A sequence of studies is reviewed that reported the domestic horse (Equus caballus) mare as an appropriate and accessible research platform for recording clinical and laboratory data post-immunisation with anti- GnRH and -zona pellucida (ZP) immunocontraceptive vaccines. Experience with a native porcine ZP (pZP) vaccine in African elephant (Loxodonta africana) cows highlighted needs for improving vaccine formulations and more clearly defining associated ovarian effects and safety profiles. Initially, the efficacy, reversibility and safety of the GnRH vaccine Improvac® in mares was demonstrated using reproductive tract ultrasonography and concurrently measuring serum antibody titres and progesterone concentrations. Results informed the study design and minimally invasive monitoring of post-treatment ovarian steroid responses of this vaccine in free-ranging African elephant cows. A subsequent sequence of studies reported reversible contraceptive and immunological efficacy in pony mares immunised with pZP formulated with Freund’s adjuvants. By comparison, mares treated with a recombinant ZP3 and ZP4 (reZP) vaccine showed disappointing responses. Unexpectedly, most pZP-treated mares showed ovarian inactivity. In attempting to understand this response, results showed the involvement of cytotoxic (CD8+) T-cells negatively correlated to serum ovarian steroid and anti-Müllerian hormone (AMH) levels. Of concern was the prevalence of injection-site lesions ascribable to Freund’s adjuvants. Following this, mares treated with both pZP and a novel reZP vaccine formulated with non-Freund’s adjuvants showed comparable immunological responses and ovarian inactivity, notably without adverse treatment reactions. In addition, measuring AMH showed promise for monitoring ovarian function in anti-ZP-treated animals

The Inflationary Paradigm: Predictions for CMB

We review why the search for a causal explanation of the large scale properties of the universe supports the idea that an extended period of accelerated expansion, called inflation, preceded primordial nucleosynthesis. As a consequence of inflation, all pre-existing classical structures are washed out, and the primordial density fluctuations (the seeds of the large scale structures) result from the amplification of vacuum quantum fluctuations. The properties of the spectrum are derived and compared to those of the spectrum of CMB anisotropies. The agreement is striking.Comment: 15 pages, 2 figures, review articl

A novel bispecific antibody for HER2+ breast cancer: The BEAT GBR 1302

While the idea of bispecific drugs was brought up over 30 years ago, the development of formats mature enough for the clinic remained for a long time a challenge. The whole field has been hampered by major problems of manufacturability (e.g. product purity and yields) and immunogenicity. With the recent arrival of new bispecific formats, either as antibody–like molecules (containing an Fc) or scFv fragments, at least 18 bispecific molecules have entered clinical trials showing very promising results. The BEAT® format has been developed as bispecific antibodies maintaining the pharmacokinetics and the low immunogenicity of human IgG with excellent manufacturability properties. In brief, the molecule is asymmetric consisting of a Hc, a Lc and a Fc-scFv. A proprietary engineered CH3 interface mimics the natural association of the heterodimeric TCRα β chains driving heterodimerization of the Hc and Fc-scFv. CHO cell lines are generated with a volumetric productivity of several g/L and a high product purity (e.g. \u3e90% of bispecific product). Based on a built-in purification approach the BEAT molecules can be purified using a standard DSP process with yield and purity comparable to standard mAbs. The presentation will highlight a new bispecific drug targeting HER2 on tumor cellsand CD3 on cytotoxic T-cells: the GBR 1302-BEAT molecule. GBR 1302-BEAT effectively recruits cytotoxic T cells against HER2 positive breast cancer cells including the trastuzumab-resistant breast cancer cell line JIMT-1. It shows strong tumor cell lysis activity with a better in vitro potential than current HER2-targeting therapies including the ADC TDM-1. The differential killing efficacy both in vitro and in vivo of HER2 overexpressing (3+) and normal, HER2 (0) cells reveals a large therapeutic window. In addition GBR 1302 does not trigger non-specific T cell activation. The excellent manufacturing attributes and the pre-clinical efficacy and safety of GBR1302 justify further clinical development as a treatment for HER2 positive cancers

A robust method for fitting peculiar velocity field models

We present a new method for fitting peculiar velocity models to complete flux limited magnitude-redshifts catalogues, using the luminosity function of the sources as a distance indicator.The method is characterised by its robustness. In particular, no assumptions are made concerning the spatial distribution of sources and their luminosity function. Moreover, selection effects in redshift are allowed. Furthermore the inclusion of additional observables correlated with the absolute magnitude -- such as for example rotation velocity information as described by the Tully-Fisher relation -- is straightforward. As an illustration of the method, the predicted IRAS peculiar velocity model characterised by the density parameter beta is tested on two samples. The application of our method to the Tully-Fisher MarkIII MAT sample leads to a value of beta=0.6 \pm 0.125, fully consistent with the results obtained previously by the VELMOD and ITF methods on similar datasets. Unlike these methods however, we make a very conservative use of the Tully-Fisher information. Specifically, we require to assume neither the linearity of the Tully-Fisher relation nor a gaussian distribution of its residuals. Moreover, the robustness of the method implies that no Malmquist corrections are required. A second application is carried out, using the fluxes of the IRAS 1.2 Jy sample as the distance indicator. In this case the effective depth of the volume in which the velocity model is compared to the data is almost twice the effective depth of the MarkIII MAT sample. The results suggest that the predicted IRAS velocity model, while successful in reproducing locally the cosmic flow, fails to describe the kinematics on larger scales.Comment: 10 pages, 14 figures, MNRAS in pres

The cloud-in-cloud problem for non-Gaussian density fields

The cloud-in-cloud problem is studied in the context of the extension to non-Gaussian density fields of the Press-Schechter approach for the calculation of the mass function. As an example of a non-Gaussian probability distribution functions (PDFs) we consider the Chi-square, with various degrees of freedom. We generate density fields in cubic boxes with periodic boundary conditions and then determine the number of points considered collapsed at each scale through an hierarchy of smoothing windows. We find that the mass function we obtain differs from that predicted using the Extended Press-Schechter formalism, particularly for low values of $\sigma$ and for those PDFs most distinct from a Gaussian.Comment: 5 pages, LaTex using mn.sty, matches published version, results for the Inverted Chi-square distribution withdraw