On Adaptive Security of Delayed-Input Sigma Protocols and Fiat-Shamir NIZKs

We study adaptive security of delayed-input Sigma protocols and non-interactive zero-knowledge (NIZK) proof systems in the common reference string (CRS) model. Our contributions are threefold: - We exhibit a generic compiler taking any delayed-input Sigma protocol and returning a delayed-input Sigma protocol satisfying adaptive-input special honest-verifier zero-knowledge (SHVZK). In case the initial Sigma protocol also satisfies adaptive-input special soundness, our compiler preserves this property. - We revisit the recent paradigm by Canetti et al. (STOC 2019) for obtaining NIZK proof systems in the CRS model via the Fiat-Shamir transform applied to so-called trapdoor Sigma protocols, in the context of adaptive security. In particular, assuming correlation-intractable hash functions for all sparse relations, we prove that Fiat- Shamir NIZKs satisfy either: (i) Adaptive soundness (and non-adaptive zero-knowledge), so long as the challenge is obtained by hashing both the prover’s first round and the instance being proven; (ii) Adaptive zero-knowledge (and non-adaptive soundness), so long as the challenge is obtained by hashing only the prover’s first round, and further assuming that the initial trapdoor Sigma protocol satisfies adaptive-input SHVZK. - We exhibit a generic compiler taking any Sigma protocol and returning a trapdoor Sigma protocol. Unfortunately, this transform does not preserve the delayed-input property of the initial Sigma protocol (if any). To complement this result, we also give yet another compiler taking any delayed-input trapdoor Sigma protocol and returning a delayed-input trapdoor Sigma protocol with adaptive-input SHVZK. An attractive feature of our first two compilers is that they allow obtaining efficient delayed-input Sigma protocols with adaptive security, and efficient Fiat-Shamir NIZKs with adaptive soundness (and non-adaptive zero-knowledge) in the CRS model. Prior to our work, the latter was only possible using generic NP reductions

Severe and fatal measles-associated pneumonia during an outbreak in Italy: data from the heart of the epidemic

Introduction: Measles is a contagious disease that re-emerged among young adults as a consequence of suboptimal vaccination coverage. Since in the pre-vaccination era measles affected mainly children, little is known about measles-associated respiratory complications in adults. The aim of this study was to describe clinical and radiological findings in adults affected by measles who developed respiratory complications during a recent measles outbreak. Material and methods: In this retrospective chart review-based study we analyzed data from patients admitted for measles from January to June 2018 to a large tertiary care hospital, in one of the main cities in the south of Italy. This city has been the country’s heart of the epidemic with a high morbidity and mortality rate. Results: Among 177 patients (mean age 26 ± 9 years), only 2 were vaccinated. Thirty patients (16.9%) had signs of pneumonia on chest radiography. Computed tomography scan showed the following abnormalities: centrilobular nodules (63%), ground-glass attenuation (63%), air-space consolidation (36%), pleural effusion (16%) and pneumothorax (10%). Five patients developed severe lung injury and hypoxemia requiring admission to Intensive Care Unit. Two young unvaccinated women with no past medical history died from acute respiratory failure. The death was sudden and unpredictable. Conclusions: Measles-associated pneumonia in unvaccinated young adults can cause severe respiratory impairment and death. Our findings support the need for a mandatory vaccination policy

New Product Development: a review of the main contributions in the last ten years of research

Research on new product development have increased enormously over the last 10 years. As markets are becoming increasingly fluid and unstable, companies had to become more flexible and de-structured, thereby trying to overcome traditional approaches which used to interpret new product development as a process formed by a linear sequence of successive stages, traditionally undertaken within corporate boundaries. Based on these considerations, this study offers an overview of the evolution of the management literature regarding new product development, published over the last 10 years (2008-2018) in peer-reviewed journals. When applying a bibliometric analysis, we have discovered the existence of five clearly defined research clusters which we have investigated by reviewing the most relevant contributions. Also, the analysis has helped us to uncover the existence of promising research areas that have been little explored. As a result, we formulated some suggestions for further research to fill the existing gaps

New Product Development During the Last Ten Years: The Ongoing Debate and Future Avenues

Research on new product development (NPD) has grown considerably over the last 30 years interweaving with serval fields of study such as strategy, marketing, supply chain management, and project management. This study offers an overview of the development of the NPD management literature published over the last ten years (2008 to 2018) in 1,226 peer-reviewed articles. By applying bibliometric analysis, we have discovered the existence of five research clusters focused on the following main thematic areas: the NPD process, the integration of diverse knowledge sources for NPD optimization, the relationship between NPD and corporate strategy, the role of users and consumers in the NPD process, the supplier involvement in the NPD activities. In respect of each area, we selected and reviewed the most relevant contributions and presented the emerging theoretical approaches and best practices. Also, the analysis has helped us to uncover the existence of promising research areas that have been scarcely explored. As a result, we formulated some suggestions for further research to fill in the existing gaps

Regulation of Erythropoietin Receptor Activity in Endothelial Cells by Different Erythropoietin (EPO) Derivatives: An in Vitro Study.

In endothelial cells, erythropoietin receptors (EPORs) mediate the protective, proliferative and angiogenic effects of EPO and its analogues, which act as EPOR agonists. Because hormonal receptors undergo functional changes upon chronic exposure to agonists and because erythropoiesis-stimulating agents (ESAs) are used for the long-term treatment of anemia, it is critical to determine the mechanism by which EPOR responsiveness is regulated at the vascular level after prolonged exposure to ESAs. Here, we investigated EPOR desensitization/resensitization in human umbilical vein endothelial cells (HUVECs) upon exposure to three ESAs with different pharmacokinetic profiles, epoetin alpha (EPOα), darbepoetin alpha (DarbEPO) and continuous EPOR activator (CERA). These agonists all induced activation of the transcription factor STAT-5, which is a component of the intracellular pathway associated with EPORs. STAT-5 activation occurred with either monophasic or biphasic kinetics for EPOα/DarbEPO and CERA, respectively. ESAs, likely through activation of the STAT-5 pathway, induced endothelial cell proliferation and stimulated angiogenesis in vitro, demonstrating a functional role for epoetins on endothelial cells. All epoetins induced EPOR desensitization with more rapid kinetics for CERA compared to EPOα and DarbEPO. However, the recovery of receptor responsiveness was strictly dependent on the type of epoetin, the agonist concentration and the time of exposure to the agonist. EPOR resensitization occurred with more rapid kinetics after exposure to low epoetin concentrations for a short period of desensitization. When the highest concentration of agonists was tested, the recovery of receptor responsiveness was more rapid with CERA compared to EPOα and was completely absent with DarbEPO. Our results demonstrate that these three ESAs regulate EPOR resensitization by very different mechanisms and that both the type of molecule and the length of EPOR stimulation are factors that are critical for the control of EPOR functioning in endothelial cells. The differences observed in receptor resensitization after stimulation with the structurally different ESAs are most likely due different control mechanisms of receptor turnover at the intracellular level

Online/Offline OR Composition of Sigma Protocols

Proofs of partial knowledge allow a prover to prove knowledge of witnesses for k out of n instances of NP languages. Cramer, Schoenmakers and Damgård [10] provided an efficient construction of a 3-round public-coin witness-indistinguishable (k, n)-proof of partial knowledge for any NP language, by cleverly combining n executions of Σ-protocols for that language. This transform assumes that all n instances are fully specified before the proof starts, and thus directly rules out the possibility of choosing some of the instances after the first round. Very recently, Ciampi et al. [6] provided an improved transform where one of the instances can be specified in the last round. They focus on (1, 2)-proofs of partial knowledge with the additional feature that one instance is defined in the last round, and could be adaptively chosen by the verifier. They left as an open question the existence of an efficient (1, 2)-proof of partial knowledge where no instance is known in the first round. More in general, they left open the question of constructing an efficient (k, n)-proof of partial knowledge where knowledge of all n instances can be postponed. Indeed, this property is achieved only by inefficient constructions requiring NP reductions [19]. In this paper we focus on the question of achieving adaptive-input proofs of partial knowledge. We provide through a transform the first efficient construction of a 3-round public-coin witness-indistinguishable (k, n)-proof of partial knowledge where all instances can be decided in the third round. Our construction enjoys adaptive-input witness indistinguishability. Additionally, the proof of knowledge property remains also if the adversarial prover selects instances adaptively at last round as long as our transform is applied to a proof of knowledge belonging to the widely used class of proofs of knowledge described in [9,21]. Since knowledge of instances and witnesses is not needed before the last round, we have that the first round can be precomputed and in the online/offline setting our performance is similar to the one of [10]. Our new transform relies on the DDH assumption (in contrast to the transforms of [6,10] that are unconditional)

Severe and Fatal Measles-Associated Pneumonia during an Outbreak in Italy: Data from the Heart of the Epidemic

Introduction: Measles is a contagious disease that re-emerged among young adults as a consequence of suboptimal vaccination coverage. Since in the pre-vaccination era measles affected mainly children, little is known about measles-associated respiratory complications in adults. The aim of this study was to describe clinical and radiological findings in adults affected by measles who developed respiratory complications during a recent measles outbreak. Material and methods: In this retrospective chart review-based study we analyzed data from patients admitted for measles from January to June 2018 to a large tertiary care hospital, in one of the main cities in the south of Italy. This city has been the country’s heart of the epidemic with a high morbidity and mortality rate. Results: Among 177 patients (mean age 26 ± 9 years), only 2 were vaccinated. Thirty patients (16.9%) had signs of pneumonia on chest radiography. Computed tomography scan showed the following abnormalities: centrilobular nodules (63%), ground-glass attenuation (63%), air-space consolidation (36%), pleural effusion (16%) and pneumothorax (10%). Five patients developed severe lung injury and hypoxemia requiring admission to Intensive Care Unit. Two young unvaccinated women with no past medical history died from acute respiratory failure. The death was sudden and unpredictable. Conclusions: Measles-associated pneumonia in unvaccinated young adults can cause severe respiratory impairment and death. Our findings support the need for a mandatory vaccination policy

Regulation of PC12 cell survival and differentiation by the new P2Y-like receptor GPR17

The P2Y-like receptor GPR17 has been reported to respond to both uracil nucleotides and cysteinyl-leukotrienes (cysLTs), such as UDP-glucose and LTD(4). Our previous data suggest a potential role for GPR17 in regulation of both cell viability and differentiation state of central nervous system cells. On this basis, in the present paper we investigated the effect of GPR17 receptor ligands on PC12 cell viability, following induction of morphological differentiation by nerve growth factor (NGF). In addition, the role of GPR17 ligands, either alone or in combination with growth factors, on the degree of PC12 cell differentiation was investigated. GPR17, which was not basally expressed in undifferentiated PC12 cells, was specifically induced by a 10day-treatment with NGF, suggesting a role in the control of neuronal specification. Both UDP-glucose and LTD(4), agonists at the nucleotide and cysLT GPR17 binding sites, respectively, induced a significant pro-survival effect on PC12 cells after priming with NGF. By in vitro silencing experiments with specific small interfering RNAs and by using receptor antagonists, we confirmed that the agonist effects are indeed mediated by the selective activation of GPR17. We also demonstrated that GPR17 agonists act, both alone and synergistically with NGF, to promote neurite outgrowth in PC12 cells. In addition, GPR17 ligands were able to confer an NGF-like activity to the epidermal growth factor (EGF), that, under these experimental conditions, also promoted cell differentiation and neurite elongation. Finally, we show that GPR17 ligands activate the intracellular phosphorylation of both ERK 1/2 and p38 kinases, that have been identified as important signalling pathways for neurotrophins in PC12 cells. Our results establish GPR17 as a neurotrophic regulator for neuronal-like cells and suggest a possible interplay between endogenous uracil derivatives, cysLTs and NGF in the signalling pathways involved in neuronal survival and differentiation. They also represent the first direct demonstration, in a native system, that GPR17 can indeed be activated by uracil nucleotides and cysLTs, in line with what previously demonstrated in recombinant expression systems

Regulation of PC12 cell survival and differentiation by the new P2Y-like receptor GPR17

he P2Y-like receptor GPR17 has been reported to respond to both uracil nucleotides and cysteinyl-leukotrienes (cysLTs), such as UDP-glucose and LTD(4). Our previous data suggest a potential role for GPR17 in regulation of both cell viability and differentiation state of central nervous system cells. On this basis, in the present paper we investigated the effect of GPR17 receptor ligands on PC12 cell viability, following induction of morphological differentiation by nerve growth factor (NGF). In addition, the role of GPR17 ligands, either alone or in combination with growth factors, on the degree of PC12 cell differentiation was investigated. GPR17, which was not basally expressed in undifferentiated PC12 cells, was specifically induced by a 10 day-treatment with NGF, suggesting a role in the control of neuronal specification. Both UDP-glucose and LTD(4), agonists at the nucleotide and cysLT GPR17 binding sites, respectively, induced a significant pro-survival effect on PC12 cells after priming with NGF. By in vitro silencing experiments with specific small interfering RNAs and by using receptor antagonists, we confirmed that the agonist effects are indeed mediated by the selective activation of GPR17. We also demonstrated that GPR17 agonists act, both alone and synergistically with NGF, to promote neurite outgrowth in PC12 cells. In addition, GPR17 ligands were able to confer an NGF-like activity to the epidermal growth factor (EGF), that, under these experimental conditions, also promoted cell differentiation and neurite elongation. Finally, we show that GPR17 ligands activate the intracellular phosphorylation of both ERK 1/2 and p38 kinases, that have been identified as important signalling pathways for neurotrophins in PC12 cells. Our results establish GPR17 as a neurotrophic regulator for neuronal-like cells and suggest a possible interplay between endogenous uracil derivatives, cysLTs and NGF in the signalling pathways involved in neuronal survival and differentiation. They also represent the first direct demonstration, in a native system, that GPR17 can indeed be activated by uracil nucleotides and cysLTs, in line with what previously demonstrated in recombinant expression systems