Israel 1983: A Bout of Unpleasant Monetarist Arithmetic

From 1970 to 1985, Israel experienced high inflation. It rose in three jumps to new plateaus and eventually exceeded 400% per annum. This paper claims that anticipated monetary and fiscal effects of a massive government bailout of owners of fallen bank shares caused the last big jump in inflation that occurred in October 1983. Bank shares had just collapsed after a scandal in which it was revealed that banks had long manipulated their share prices. The government promised to reimburse innocent owners for the diminished value of their bank shares, but only after four or five years. The public believed that promise and public debt therefore implicitly increased by a large amount. That implied future monetary expansions. Because that was foreseen, inflation immediately rose as predicted by the unpleasant monetarist arithmetic of Sargent and Wallace (1981).From 1970 to 1985, Israel experienced high inflation. It rose in three jumps to new plateaus and eventually exceeded 400% per annum. This paper claims that anticipated monetary and fiscal effects of a massive government bailout of owners of fallen bank shares caused the last big jump in inflation that occurred in October 1983. Bank shares had just collapsed after a scandal in which it was revealed that banks had long manipulated their share prices. The government promised to reimburse innocent owners for the diminished value of their bank shares, but only after four or five years. The public believed that promise and public debt therefore implicitly increased by a large amount. That implied future monetary expansions. Because that was foreseen, inflation immediately rose as predicted by the unpleasant monetarist arithmetic of Sargent and Wallace (1981).Non-Refereed Working Papers / of national relevance onl

Genome Halving and Aliquoting Under the Copy Number Distance

Large-scale genome rearrangements occur frequently in species evolution and cancer evolution. While the computation of evolutionary distances is tractable for balanced rearrangements, such as inversions and translocations, computing distances involving duplications and deletions is much more difficult. In the recently proposed Copy Number Distance (CND) model, a genome is represented as a Copy Number Profile (CNP), a sequence of integers, and the CND between two CNPs is the length of a shortest sequence of deletions and amplifications of contiguous segments that transforms one CNP into the other. In addition to these segmental events, genomes also undergo global events such as Whole Genome Duplication (WGD) or polyploidization that multiply the entire genome content. These global events are common and important in both species and cancer evolution. In this paper, we formulate the genome halving problem of finding a closest preduplication CNP that has undergone a WGD and evolved into a given CNP under the CND model. We also formulate the analogous genome aliquoting problem of finding the closest prepolyploidzation CNP under the CND distance. We give a linear time algorithm for the halving distance and a quadratic time dynamic programming algorithm for the aliquoting distance. We implement these algorithms and show that they produce reasonable solutions on simulated CNPs

Identification of a class of non-conventional ER-stress-response-derived immunogenic peptides

Efforts to overcome resistance to immune checkpoint blockade therapy have focused on vaccination strategies using neoepitopes, although they cannot be applied on a large scale due to the “private” nature of cancer mutations. Here, we show that infection of tumor cells with Salmonella induces the opening of membrane hemichannels and the extracellular release of proteasome-generated peptides by the exacerbation of endoplasmic reticulum (ER) stress. Peptides released by cancer cells foster an antitumor response in vivo, both in mice bearing B16F10 melanomas and in dogs suffering from osteosarcoma. Mass spectrometry analysis on the supernatant of human melanoma cells revealed 12 peptides capable of priming healthy-donor CD8+ T cells that recognize and kill human melanoma cells in vitro and when xenotransplanted in vivo. Hence, we identified a class of shared tumor antigens that are generated in ER-stressed cells, such as tumor cells, that do not induce tolerance and are not presented by healthy cells

Identification of a class of non-conventional ER-stress-response-derived immunogenic peptides

Efforts to overcome resistance to immune checkpoint blockade therapy have focused on vaccination strategies using neoepitopes, although they cannot be applied on a large scale due to the “private” nature of cancer mutations. Here, we show that infection of tumor cells with Salmonella induces the opening of membrane hemichannels and the extracellular release of proteasome-generated peptides by the exacerbation of endoplasmic reticulum (ER) stress. Peptides released by cancer cells foster an antitumor response in vivo, both in mice bearing B16F10 melanomas and in dogs suffering from osteosarcoma. Mass spectrometry analysis on the supernatant of human melanoma cells revealed 12 peptides capable of priming healthy-donor CD8+ T cells that recognize and kill human melanoma cells in vitro and when xenotransplanted in vivo. Hence, we identified a class of shared tumor antigens that are generated in ER-stressed cells, such as tumor cells, that do not induce tolerance and are not presented by healthy cells

Feasibility study of parameter estimation of random sampling jitter using the bispectrum

An actual sampling process can be modeled as a random process, which consists of the regular (uniform) deterministic sampling process plus an error in the sampling times which constitutes a zero-mean noise (the jitter). In this paper we discuss the problem of estimating the jitter process. By assuming that the jitter process is an i.i.d. one, with standard deviation that is small compared to the regular sampling time, we show that the variance of the jitter process can be estimated from the n th order spectrum of the sampled data, n =2, 3, i.e., the jitter variance can be extracted from the 2nd-order spectrum or the 3rd-order spectrum (the bispectrum) of the sampled data, provided the continuous signal spectrum is known. However when the signal skewness exceeds a certain level, the potential performance of the bispectrum-based estimation is better than that of the spectrum-based estimation. Moreover, the former can also provide jitter variance estimates when the continuous signal spectrum is unknown while the latter cannot. This suggests that the bispectrum of the sampled data is potentially better for estimating any parameter of the sampling jitter process, once the signal skewness is sufficiently large.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/43577/1/34_2005_Article_BF01183740.pd

A Weak Neutralizing Antibody Response to Hepatitis C Virus Envelope Glycoprotein Enhances Virus Infection

We have completed a phase 1 safety and immunogenicity trial with hepatitis C virus (HCV) envelope glycoproteins, E1 and E2, with MF59 adjuvant as a candidate vaccine. Neutralizing activity to HCV genotype 1a was detected in approximately 25% of the vaccinee sera. In this study, we evaluated vaccinee sera from poor responders as a potential source of antibody dependent enhancement (ADE) of HCV infection. Sera with poor neutralizing activity enhanced cell culture grown HCV genotype 1a or 2a, and surrogate VSV/HCV pseudotype infection titer, in a dilution dependent manner. Surrogate pseudotypes generated from individual HCV glycoproteins suggested that antibody to the E2 glycoprotein; but not the E1 glycoprotein, was the principle target for enhancing infection. Antibody specific to FcRII expressed on the hepatic cell surface or to the Fc portion of Ig blocked enhancement of HCV infection by vaccinee sera. Together, the results from in vitro studies suggested that enhancement of viral infectivity may occur in the absence of a strong antibody response to HCV envelope glycoproteins

Interaction between CXCR4 and CCL20 Pathways Regulates Tumor Growth

The chemokine receptor CXCR4 and its ligand CXCL12 is overexpressed in the majority of tumors and is critically involved in the development and metastasis of these tumors. CXCR4 is expressed in malignant tumor cells whereas its ligand SDF-1 (CXCL12) is expressed mainly by cancer associated fibroblasts (CAF). Similarly to CXCR4, the chemokine CCL20 is overexpressed in variety of tumors; however its role and regulation in tumors is not fully clear. Here, we show that the chemokine receptor CXCR4 stimulates the production of the chemokine CCL20 and that CCL20 stimulates the proliferation and adhesion to collagen of various tumor cells. Furthermore, overexpression of CCL20 in tumor cells promotes growth and adhesion in vitro and increased tumor growth and invasiveness in vivo. Moreover, neutralizing antibodies to CCL20 inhibit the in vivo growth of tumors that either overexpress CXCR4 or CCL20 or naturally express CCL20. These results reveal a role for CCL20 in CXCR4-dependent and -independent tumor growth and suggest a therapeutic potential for CCL20 and CCR6 antagonists in the treatment of CXCR4- and CCL20-dependent malignancies