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The BUFF transform is a generic transformation for digital signature schemes, with the purpose of obtaining additional security properties beyond standard unforgeability, e.g., exclusive ownership and non-resignability. In the call for additional post-quantum signatures, these were explicitly mentioned by the NIST as “additional desirable security properties”, and some of the submissions indeed refer to the BUFF transform with the purpose of achieving them, while some other submissions follow the design of the BUFF transform without mentioning it explicitly. In this work, we show the following negative results regarding the non-resignability property in general, and the BUFF transform in particular. In the plain model, we observe by means of a simple attack that any signature scheme for which the message has a high entropy given the signature does not satisfy the non-resignability property (while non-resignability is trivially not satisfied if the message can be efficiently computed from its signature). Given that the BUFF transform has high entropy in the message given the signature, it follows that the BUFF transform does not achieve non-resignability whenever the random oracle is instantiated with a hash function, no matter what hash function. When considering the random oracle model (ROM), the matter becomes slightly more delicate since prior works did not rigorously define the non-resignability property in the ROM. For the natural extension of the definition to the ROM, we observe that our impossibility result still holds, despite there having been positive claims about the non-resignability of the BUFF transform in the ROM. Indeed, prior claims of the non-resignability of the BUFF transform rely on faulty argumentation. On the positive side, we prove that a salted version of the BUFF transform satisfies a slightly weaker variant of non-resignability in the ROM, covering both classical and quantum attacks, if the entropy requirement in the (weakened) definition

Contains fulltext : 295958.pdf (Publisher’s version ) (Open Access), PURPOSE: There is an unmet need for therapeutic options that prolong survival for patients with heavily pretreated, metastatic castration-resistant prostate cancer (mCRPC). The phase III, open-label KEYLYNK-010 study evaluated pembrolizumab plus olaparib versus a next-generation hormonal agent (NHA) for biomarker-unselected, previously treated mCRPC. METHODS: Eligible participants had mCRPC that progressed on or after abiraterone or enzalutamide (but not both) and docetaxel. Participants were randomly assigned (2:1) to pembrolizumab plus olaparib or NHA (abiraterone or enzalutamide). The dual primary end points were radiographic progression-free survival (rPFS) by blinded independent central review per Prostate Cancer Working Group-modified RECIST 1.1 and overall survival (OS). Time to first subsequent therapy (TFST) was a key secondary end point. Safety and objective response rate (ORR) were secondary end points. RESULTS: Between May 30, 2019, and July 16, 2021, 529 participants were randomly assigned to pembrolizumab plus olaparib and 264 to NHA. At final rPFS analysis, median rPFS was 4.4 months (95% CI, 4.2 to 6.0) with pembrolizumab plus olaparib and 4.2 months (95% CI, 4.0 to 6.1) with NHA (hazard ratio [HR], 1.02 [95% CI, 0.82 to 1.25]; P = .55). At final OS analysis, median OS was 15.8 months (95% CI, 14.6 to 17.0) and 14.6 months (95% CI, 12.6 to 17.3), respectively (HR, 0.94 [95% CI, 0.77 to 1.14]; P = .26). At final TFST analysis, median TFST was 7.2 months (95% CI, 6.7 to 8.1) versus 5.7 months (95% CI, 5.0 to 7.1), respectively (HR, 0.86 [95% CI, 0.71 to 1.03]). ORR was higher with pembrolizumab plus olaparib versus NHA (16.8% v 5.9%). Grade ≥3 treatment-related adverse events occurred in 34.6% and 9.0% of participants, respectively. CONCLUSION: Pembrolizumab plus olaparib did not significantly improve rPFS or OS versus NHA in participants with biomarker-unselected, heavily pretreated mCRPC. The study was stopped for futility. No new safety signals occu

The BUFF transform is a generic transformation for digital signature schemes, with the purpose of obtaining additional security properties beyond standard unforgeability, e.g., exclusive ownership and non-resignability. In the call for additional post-quantum signatures, these were explicitly mentioned by the NIST as ``additional desirable security properties'', and some of the submissions indeed refer to the BUFF transform with the purpose of achieving them, while some other submissions follow the design of the BUFF transform without mentioning it explicitly. In this work, we show the following negative results regarding the non-resignability property in general, and the BUFF transform in particular. In the plain model, we observe by means of a simple attack that any signature scheme for which the message has a high entropy given the signature does not satisfy the non-resignability property (while non-resignability is trivially not satisfied if the message can be efficiently computed from its signature). Given that the BUFF transform has high entropy in the message given the signature, it follows that the BUFF transform does not achieve non-resignability whenever the random oracle is instantiated with a hash function, no matter what hash function. When considering the random oracle model (ROM), the matter becomes slightly more delicate since prior works did not rigorously define the non-resignability property in the ROM. For the natural extension of the definition to the ROM, we observe that our impossibility result still holds, despite there having been positive claims about the non-resignability of the BUFF transform in the ROM. Indeed, prior claims of the non-resignability of the BUFF transform rely on faulty argumentation. On the positive side, we prove that a salted version of the BUFF transform satisfies a slightly weaker variant of non-resignability in the ROM, covering both classical and quantum attacks, if the entropy requirement in the (weakened) definiti

In this paper, we prove the quantum security of the signature scheme HAWK, proposed by Ducas, Postlethwaite, Pulles and van Woerden (ASIACRYPT 2022). More precisely, we reduce its strong unforgeability in the quantum random oracle model (QROM) to the hardness of the one-more SVP problem, which is the computational problem on which also the classical security analysis of HAWK relies. Our security proof deals with the quantum aspects in a rather black-box way, making it accessible also to non-quantum-experts.

We extend and consolidate the security justification for the Dilithium signature scheme. In particular, we identify a subtle but crucial gap that appears in several ROM and QROM security proofs for signature schemes that are based on the Fiat-Shamir with aborts paradigm, including Dilithium. The gap lies in the CMA-to-NMA reduction and was uncovered when trying to formalize a variant of the QROM security proof by Kiltz, Lyubashevsky, and Schaffner (Eurocrypt 2018). The gap was confirmed by the authors, and there seems to be no simple patch for it. We provide new, fixed proofs for the affected CMA-to-NMA reduction, both for the ROM and the QROM, and we perform a concrete security analysis for the case of Dilithium to show that the claimed security level is still valid after addressing the gap. Furthermore, we offer a fully mechanized ROM proof for the CMA-security of Dilithium in the EasyCrypt proof assistant. Our formalization includes several new tools and techniques of independent interest for future formal verification results.

In the first part of the paper, we show a generic compiler that transforms any oracle algorithm that can query multiple oracles adaptively, i.e., can decide on which oracle to query at what point dependent on previous oracle responses, into a static algorithm that fixes these choices at the beginning of the execution. Compared to naive ways of achieving this, our compiler controls the blow-up in query complexity for each oracle individually, and causes a very mild blow-up only. In the second part of the paper, we use our compiler to show the security of the very efficient hash-based split-key PRF proposed by Giacon, Heuer and Poettering (PKC 2018), in the quantum random-oracle model. Using a split-key PRF as the key-derivation function gives rise to a secure KEM combiner. Thus, our result shows that the hash-based construction of Giacon et al. can be safely used in the context of quantum attacks, for instance to combine a well-established but only classically-secure KEM with a candidate KEM that is believed to be quantum-secure. Our security proof for the split-key PRF crucially relies on our adaptive-to-static compiler, but we expect our compiler to be useful beyond this particular application. Indeed, we discuss a couple of other, known results from the literature that would have profitted from our compiler, in that these works had to go though serious complications in order to deal with adaptivity.

We revisit the so-called compressed oracle technique, introduced by Zhandry for analyzing quantum algorithms in the quantum random oracle model (QROM). To start off with, we offer a concise exposition of the technique, which easily extends to the parallel-query QROM, where in each query-round the considered algorithm may make several queries to the QROM in parallel. This variant of the QROM allows for a more fine-grained query-complexity analysis. Our main technical contribution is a framework that simplifies the use of (the parallel-query generalization of) the compressed oracle technique for proving query complexity results. With our framework in place, whenever applicable, it is possible to prove quantum query complexity lower bounds by means of purely classical reasoning. More than that, for typical examples the crucial classical observations that give rise to the classical bounds are sufficient to conclude the corresponding quantum bounds. We demonstrate this on a few examples, recovering known results but also obtaining new results. Our main target is the hardness of finding a q-chain with fewer than q parallel queries, i.e., a sequence x0, x1, …, xq with xi= H(xi-1) for all 1 ≤ i≤ q. The above problem of finding a hash chain is of fundamental importance in the context of proofs of sequential work. Indeed, as a concrete cryptographic application of our techniques, we prove quantum security of the “Simple Proofs of Sequential Work” by Cohen and Pietrzak.

We revisit the so-called compressed oracle technique, introduced by Zhandry for analyzing quantum algorithms in the quantum random oracle model (QROM). To start off with, we offer a concise exposition of the technique, which easily extends to the parallel-query QROM, where in each query-round the considered algorithm may make several queries to the QROM in parallel. This variant of the QROM allows for a more fine-grained query-complexity analysis. Our main technical contribution is a framework that simplifies the use of (the parallel-query generalization of) the compressed oracle technique for proving query complexity results. With our framework in place, whenever applicable, it is possible to prove quantum query complexity lower bounds by means of purely classical reasoning. More than that, for typical examples the crucial classical observations that give rise to the classical bounds are sufficient to conclude the corresponding quantum bounds. We demonstrate this on a few examples, recovering known results but also obtaining new results. Our main target is the hardness of finding a q-chain with fewer than q parallel queries, i.e., a sequence x0, x1, …, xq with xi= H(xi-1) for all 1 ≤ i≤ q. The above problem of finding a hash chain is of fundamental importance in the context of proofs of sequential work. Indeed, as a concrete cryptographic application of our techniques, we prove quantum security of the “Simple Proofs of Sequential Work” by Cohen and Pietrzak.

The general approach for taking into account the processing induced residual stress in mechanical design and the structure health monitoring involves research in three fields: process development, residual stress determination and numerical tools. The destructive (incremental hole drilling method) and non-destructive (x-ray, neutron diffraction, ultrasonic) methods have been combined in order to evaluate precisely the residual stresses distribution. Some new results concerning the new development of the optical methods for the in depth residual stress distribution measurement will be shown. A special attention is paid to residual stress induced in metal and polymer matrix composite materials. Then the residual stresses obtained by different techniques of thermal spraying which are widely used in the biomedical, automobile, aerospace industries will be presented. Different coating systems (Zirconia, Cr2O3, WC-Co, NiCrAlY) manufactured by different processes (HVOF, APS, VPS, ATCPS) will be shown. The residual stress induced by a novel surface mechanical attrition treatment (SMAT) will be also presented. Significant enhancements in mechanical properties of the nanostructured surface layer in metallic materials and the potential applications for large structure such as aircraft, nuclear plant and bridge repair will be analyzed and presented. ©2009 Society for Experimental Mechanics Inc.

The general approach for taking into account the processing induced residual stress in mechanical design and the structure health monitoring involves research in three fields: process development, residual stress determination and numerical tools. The destructive (incremental hole drilling method) and non-destructive (x-ray, neutron diffraction, ultrasonic) methods have been combined in order to evaluate precisely the residual stresses distribution. Some new results concerning the new development of the optical methods for the in depth residual stress distribution measurement will be shown. A special attention is paid to residual stress induced in metal and polymer matrix composite materials. Then the residual stresses obtained by different techniques of thermal spraying which are widely used in the biomedical, automobile, aerospace industries will be presented. Different coating systems (Zirconia, Cr2O3, WC-Co, NiCrAlY) manufactured by different processes (HVOF, APS, VPS, ATCPS) will be shown. The residual stress induced by a novel surface mechanical attrition treatment (SMAT) will be also presented. Significant enhancements in mechanical properties of the nanostructured surface layer in metallic materials and the potential applications for large structure such as aircraft, nuclear plant and bridge repair will be analyzed and presented. ©2009 Society for Experimental Mechanics Inc.

The general approach for taking into account the processing induced residual stress in mechanical design and the structure health monitoring involves research in three fields: process development, residual stress determination and numerical tools. The destructive (incremental hole drilling method) and non-destructive (x-ray, neutron diffraction, ultrasonic) methods have been combined in order to evaluate precisely the residual stresses distribution. Some new results concerning the new development of the optical methods for the in depth residual stress distribution measurement will be shown. A special attention is paid to residual stress induced in metal and polymer matrix composite materials. Then the residual stresses obtained by different techniques of thermal spraying which are widely used in the biomedical, automobile, aerospace industries will be presented. Different coating systems (Zirconia, Cr2O3, WC-Co, NiCrAlY) manufactured by different processes (HVOF, APS, VPS, ATCPS) will be shown. The residual stress induced by a novel surface mechanical attrition treatment (SMAT) will be also presented. Significant enhancements in mechanical properties of the nanostructured surface layer in metallic materials and the potential applications for large structure such as aircraft, nuclear plant and bridge repair will be analyzed and presented. ©2009 Society for Experimental Mechanics Inc.

Contains fulltext : 58585.pdf (publisher's version ) (Closed access), We investigated the effect of smaller dose, weight-adjusted heparin with earlier monitoring of activated partial thromboplastin time on the incidence of ischemic and hemorrhagic complications in patients with ST-elevation myocardial infarction treated with full-dose tenecteplase. We compared the outcomes of patients enrolled in the Second Assessment of the Safety and Efficacy of a New Thrombolytic Regimen (ASSENT-2; n = 8,461) who received heparin stratified by weight (patients weighing >67 kg received a 5,000-U bolus plus infusion at 1,000 U/hour; those weighing < or =67 kg received a 4,000-U bolus plus infusion at 800 U/hour) with patients in ASSENT-3 who received weight-adjusted heparin (60-U/kg bolus, maximum 4,000 U/hour, followed by a 12-U/kg/hour infusion, maximum 1,000 U/hour). Compared with patients in ASSENT-2, those in ASSENT-3 had similar rates of 30-day mortality, recurrent infarction, and intracranial hemorrhage, less major bleeding (2.2% vs 4.7%, p <0.001), and less refractory ischemia (6.5% vs 8.6%, p <0.001). After adjustment for baseline characteristics, patients in ASSENT-3 had similar rates of 30-day mortality (odds ratio [OR] 0.96, 95% confidence interval [CI] 0.77 to 1.19) and intracranial hemorrhage (OR 1.02, 95% CI 0.61 to 1.69) but less major bleeding (OR 0.49, 95% CI 0.35 to 0.67) than did patients in ASSENT-2. These findings support the use of smaller dose, weight-adjusted heparin in patients with ST-elevation myocardial infarction treated with tenecteplase.

Contains fulltext : 58585.pdf (publisher's version ) (Closed access), We investigated the effect of smaller dose, weight-adjusted heparin with earlier monitoring of activated partial thromboplastin time on the incidence of ischemic and hemorrhagic complications in patients with ST-elevation myocardial infarction treated with full-dose tenecteplase. We compared the outcomes of patients enrolled in the Second Assessment of the Safety and Efficacy of a New Thrombolytic Regimen (ASSENT-2; n = 8,461) who received heparin stratified by weight (patients weighing >67 kg received a 5,000-U bolus plus infusion at 1,000 U/hour; those weighing < or =67 kg received a 4,000-U bolus plus infusion at 800 U/hour) with patients in ASSENT-3 who received weight-adjusted heparin (60-U/kg bolus, maximum 4,000 U/hour, followed by a 12-U/kg/hour infusion, maximum 1,000 U/hour). Compared with patients in ASSENT-2, those in ASSENT-3 had similar rates of 30-day mortality, recurrent infarction, and intracranial hemorrhage, less major bleeding (2.2% vs 4.7%, p <0.001), and less refractory ischemia (6.5% vs 8.6%, p <0.001). After adjustment for baseline characteristics, patients in ASSENT-3 had similar rates of 30-day mortality (odds ratio [OR] 0.96, 95% confidence interval [CI] 0.77 to 1.19) and intracranial hemorrhage (OR 1.02, 95% CI 0.61 to 1.69) but less major bleeding (OR 0.49, 95% CI 0.35 to 0.67) than did patients in ASSENT-2. These findings support the use of smaller dose, weight-adjusted heparin in patients with ST-elevation myocardial infarction treated with tenecteplase.

Contains fulltext : 58585.pdf (publisher's version ) (Closed access), We investigated the effect of smaller dose, weight-adjusted heparin with earlier monitoring of activated partial thromboplastin time on the incidence of ischemic and hemorrhagic complications in patients with ST-elevation myocardial infarction treated with full-dose tenecteplase. We compared the outcomes of patients enrolled in the Second Assessment of the Safety and Efficacy of a New Thrombolytic Regimen (ASSENT-2; n = 8,461) who received heparin stratified by weight (patients weighing >67 kg received a 5,000-U bolus plus infusion at 1,000 U/hour; those weighing < or =67 kg received a 4,000-U bolus plus infusion at 800 U/hour) with patients in ASSENT-3 who received weight-adjusted heparin (60-U/kg bolus, maximum 4,000 U/hour, followed by a 12-U/kg/hour infusion, maximum 1,000 U/hour). Compared with patients in ASSENT-2, those in ASSENT-3 had similar rates of 30-day mortality, recurrent infarction, and intracranial hemorrhage, less major bleeding (2.2% vs 4.7%, p <0.001), and less refractory ischemia (6.5% vs 8.6%, p <0.001). After adjustment for baseline characteristics, patients in ASSENT-3 had similar rates of 30-day mortality (odds ratio [OR] 0.96, 95% confidence interval [CI] 0.77 to 1.19) and intracranial hemorrhage (OR 1.02, 95% CI 0.61 to 1.69) but less major bleeding (OR 0.49, 95% CI 0.35 to 0.67) than did patients in ASSENT-2. These findings support the use of smaller dose, weight-adjusted heparin in patients with ST-elevation myocardial infarction treated with tenecteplase.

Item does not contain fulltext, UDP-glucuronosyltransferase (UGT) 1A8 is part of the UGT1 locus and is expressed exclusively in extrahepatic tissues. Analysis of UGT1A8 exon 1 sequence has identified four genotypes from a population of 69 individuals. While there are four alleles, one of the single base pair changes leads to a silent mutation at T255, while the other mutations lead to amino acid substitutions at positions 173 and 277, creating three allelic variants. UGT1A8*1 (A173C277), UGT1A8*1a (T255A>G), UGT1A8*2 (G173C277) and UGT1A8*3 (A173Y277). The allelic frequencies of UGT1A8*1, UGT1A8*1a, UGT1A8*2 and UGT1A8*3 are 0.551, 0.282, 0.145 and 0.022, respectively. To examine the properties of the UGT1A8 proteins, UGT1A8*1 and UGT1A8*2 were cloned from a human colon cDNA library and UGT1A8*3 generated by mutagenesis using UGT1A8*1 as template. The cDNAs were expressed in HK293 cells to examine catalytic function as well as abundance as observed by analysis of UGT1A8-GFP (green fluorescent protein) expression. The single amino acid change that identifies UGT1A8*1 (A173) and UGT1A8*2 (G173) has little impact on function, while the UGT1A8*3 (Y277) is a conserved amino acid alteration represented by a dramatic reduction in catalytic activity. Protein abundance, as determined by Western blot analysis following transient transfection, is not altered. In addition, functional UGT1A8-GFP variants displayed staining in the cytoplasmic region, indicating that each protein is expressed in similar cellular compartments. Together, these data suggest that the null UGT1A8*3 results from structural changes and not a lack of protein expression. Allelic variation leading to singular codon changes could potentially alter drug metabolism in extrahepatic tissues.

Item does not contain fulltext, UDP-glucuronosyltransferase (UGT) 1A8 is part of the UGT1 locus and is expressed exclusively in extrahepatic tissues. Analysis of UGT1A8 exon 1 sequence has identified four genotypes from a population of 69 individuals. While there are four alleles, one of the single base pair changes leads to a silent mutation at T255, while the other mutations lead to amino acid substitutions at positions 173 and 277, creating three allelic variants. UGT1A8*1 (A173C277), UGT1A8*1a (T255A>G), UGT1A8*2 (G173C277) and UGT1A8*3 (A173Y277). The allelic frequencies of UGT1A8*1, UGT1A8*1a, UGT1A8*2 and UGT1A8*3 are 0.551, 0.282, 0.145 and 0.022, respectively. To examine the properties of the UGT1A8 proteins, UGT1A8*1 and UGT1A8*2 were cloned from a human colon cDNA library and UGT1A8*3 generated by mutagenesis using UGT1A8*1 as template. The cDNAs were expressed in HK293 cells to examine catalytic function as well as abundance as observed by analysis of UGT1A8-GFP (green fluorescent protein) expression. The single amino acid change that identifies UGT1A8*1 (A173) and UGT1A8*2 (G173) has little impact on function, while the UGT1A8*3 (Y277) is a conserved amino acid alteration represented by a dramatic reduction in catalytic activity. Protein abundance, as determined by Western blot analysis following transient transfection, is not altered. In addition, functional UGT1A8-GFP variants displayed staining in the cytoplasmic region, indicating that each protein is expressed in similar cellular compartments. Together, these data suggest that the null UGT1A8*3 results from structural changes and not a lack of protein expression. Allelic variation leading to singular codon changes could potentially alter drug metabolism in extrahepatic tissues.

It was found that when the activity product for hydrogen/chloride is high chromium (VI) is coextracted with HCl by triisooctylamine in the form (HCrO4)-. An extraction model to explain the experimental data is proposed and the extraction constants are determined., It was found that when the activity product for hydrogen/chloride is high chromium (VI) is coextracted with HCl by triisooctylamine in the form (HCrO4)-. An extraction model to explain the experimental data is proposed and the extraction constants are determined.

The permeation resistance of the system is mainly due to the feed aqueous film resistance. However, when the HCl concentration of the feed phase is less than 7.2 M, the permeation resistance is contributed to by both the resistances of the feed aqueous film and of the membrane., The permeation resistance of the system is mainly due to the feed aqueous film resistance. However, when the HCl concentration of the feed phase is less than 7.2 M, the permeation resistance is contributed to by both the resistances of the feed aqueous film and of the membrane.