Not All Fabrics Are Created Equal: Exploring eFPGA Parameters for IP Redaction

Semiconductor design houses rely on third-party foundries to manufacture their integrated circuits (ICs). While this trend allows them to tackle fabrication costs, it introduces security concerns as external (and potentially malicious) parties can access critical parts of the designs and steal or modify the intellectual property (IP). Embedded field-programmable gate array (eFPGA) redaction is a promising technique to protect critical IPs of an ASIC by redacting (i.e., removing) critical parts and mapping them onto a custom reconfigurable fabric. Only trusted parties will receive the correct bitstream to restore the redacted functionality. While previous studies imply that using an eFPGA is a sufficient condition to provide security against IP threats like reverse-engineering, whether this truly holds for all eFPGA architectures is unclear, thus motivating the study in this article. We examine the security of eFPGA fabrics generated by varying different FPGA design parameters. We characterize the power, performance, and area (PPA) characteristics and evaluate each fabric’s resistance to Boolean satisfiability (SAT)-based bitstream recovery. Our results encourage designers to work with custom eFPGA fabrics rather than off-the-shelf commercial FPGAs and reveals that only considering a redaction fabric’s bitstream size is inadequate for gauging security

ALICE: An Automatic Design Flow for eFPGA Redaction

Fabricating an integrated circuit is becoming unaffordable for many semiconductor design houses. Outsourcing the fabrication to a third-party foundry requires methods to protect the intellectual property of the hardware designs. Designers can rely on embedded reconfigurable devices to completely hide the real functionality of selected design portions unless the configuration string (bitstream) is provided. However, selecting such portions and creating the corresponding reconfigurable fabrics are still open problems. We propose ALICE, a design flow that addresses the EDA challenges of this problem. ALICE partitions the RTL modules between one or more reconfigurable fabrics and the rest of the circuit, automating the generation of the corresponding redacted design

Multivalued SK-contractions with respect to b-generalized pseudodistances

A new class of multivalued non-self-mappings, called SK-contractions with respect to b-generalized pseudodistances, is introduced and used to investigate the existence of best proximity points by using an appropriate geometric property. Some new fixed point results in b-metric spaces are also obtained. Examples are given to support the usability of our main result

Outcome of AIDS-associated cryptococcal meningitis initially treated with 200 mg/day or 400 mg/day of fluconazole

BACKGROUND: AIDS-associated cryptococcal meningitis has a high mortality. Fluconazole was the only systemic antifungal therapy available in our centre. From 1999–2001 we used low-dose fluconazole (200 mg daily initially), and did not offer therapy to patients perceived to have poor prognoses. In 2001 donated fluconazole became available, allowing us to use standard doses (400 mg daily initially). Antiretroviral therapy was not available during the study period. METHODS: Retrospective chart review of adult patients before and after the fluconazole donation. RESULTS: 205 patients fulfilled the inclusion criteria, 77 before and 128 after the donation. Following the donation fewer patients received no antifungal treatment (5% vs 19%, p = 0.002), and more patients received standard-dose fluconazole (90% vs 6%, p < 0.001). In-hospital mortality was 25%. Impaired consciousness, no antifungal treatment received and cerebrospinal fluid antigen titre > 1,000 were independent predictors of in-hospital mortality. Concomitant rifampicin did not affect in-hospital survival. Thirteen patients were referred to the tertiary referral hospital and received initial treatment with amphotericin B for a mean of 6 days – their in-hospital survival was not different from patients who received only fluconazole (p = 0.9). Kaplan-Meier analysis showed no differences in length of survival by initial treatment with standard or low doses of fluconazole (p = 0.27 log rank test); median survival was 76 and 82 days respectively. CONCLUSION: Outcome of AIDS-associated cryptococcal meningitis is similar with low or standard doses of fluconazole. The early mortality is high. Initial therapy with amphotericin B and other measures may be needed to improve outcome

Escape of SARS-CoV-2 501Y.V2 from neutralization by convalescent plasma

SARS-CoV-2 variants of concern (VOC) have arisen independently at multiple locations [1, 2] and may reduce the efficacy of current vaccines targeting the spike glycoprotein [3]. Here, using a live virus neutralization assay (LVNA), we compared neutralization of a non-VOC variant versus the 501Y.V2 variant using plasma collected from adults hospitalized with COVID-19 from two South African infection waves, with the second wave dominated by 501Y.V2 infections. Sequencing demonstrated that infections in first wave plasma donors were with viruses harbouring none of the 501Y.V2-defining mutations, except for one with the E484K mutation in the receptor binding domain. 501Y.V2 virus was effectively neutralized by plasma from second wave infections and first wave virus was effectively neutralized by first wave plasma. In cross-neutralization, 501Y.V2 virus was poorly neutralized by first wave plasma, with a 15.1-fold drop relative to 501Y.V2 neutralization by second wave plasma across participants. In contrast, second wave plasma cross-neutralization of first wave virus was more effective, showing only a 2.3-fold decline relative to first wave plasma neutralization of first wave virus. While we only tested one plasma elicited by E484K alone, this potently neutralized both variants. The observed effective neutralization of first wave virus by 501Y.V2 infection elicited plasma provides preliminary evidence that vaccines based on VOC sequences could retain activity against other circulating SARS-CoV-2 lineages

HIV status alters disease severity and immune cell responses in Beta variant SARS-CoV-2 infection wave

There are conflicting reports on the effects of HIV on COVID-19. Here, we analyzed disease severity and immune cell changes during and after SARS-CoV-2 infection in 236 participants from South Africa, of which 39% were people living with HIV (PLWH), during the first and second (Beta dominated) infection waves. The second wave had more PLWH requiring supplemental oxygen relative to HIV-negative participants. Higher disease severity was associated with low CD4 T cell counts and higher neutrophil to lymphocyte ratios (NLR). Yet, CD4 counts recovered and NLR stabilized after SARS-CoV-2 clearance in wave 2 infected PLWH, arguing for an interaction between SARS-CoV-2 and HIV infection leading to low CD4 and high NLR. The first infection wave, where severity in HIV negative and PLWH was similar, still showed some HIV modulation of SARS-CoV-2 immune responses. Therefore, HIV infection can synergize with the SARS-CoV-2 variant to change COVID-19 outcomes

Mutations in FGF17, IL17RD, DUSP6, SPRY4, and FLRT3 Are Identified in Individuals with Congenital Hypogonadotropic Hypogonadism

Congenital hypogonadotropic hypogonadism (CHH) and its anosmia-associated form (Kallmann syndrome [KS]) are genetically heterogeneous. Among the &gt;15 genes implicated in these conditions, mutations in FGF8 and FGFR1 account for ∼12% of cases; notably, KAL1 and HS6ST1 are also involved in FGFR1 signaling and can be mutated in CHH. We therefore hypothesized that mutations in genes encoding a broader range of modulators of the FGFR1 pathway might contribute to the genetics of CHH as causal or modifier mutations. Thus, we aimed to (1) investigate whether CHH individuals harbor mutations in members of the so-called "FGF8 synexpression" group and (2) validate the ability of a bioinformatics algorithm on the basis of protein-protein interactome data (interactome-based affiliation scoring [IBAS]) to identify high-quality candidate genes. On the basis of sequence homology, expression, and structural and functional data, seven genes were selected and sequenced in 386 unrelated CHH individuals and 155 controls. Except for FGF18 and SPRY2, all other genes were found to be mutated in CHH individuals: FGF17 (n = 3 individuals), IL17RD (n = 8), DUSP6 (n = 5), SPRY4 (n = 14), and FLRT3 (n = 3). Independently, IBAS predicted FGF17 and IL17RD as the two top candidates in the entire proteome on the basis of a statistical test of their protein-protein interaction patterns to proteins known to be altered in CHH. Most of the FGF17 and IL17RD mutations altered protein function in vitro. IL17RD mutations were found only in KS individuals and were strongly linked to hearing loss (6/8 individuals). Mutations in genes encoding components of the FGF pathway are associated with complex modes of CHH inheritance and act primarily as contributors to an oligogenic genetic architecture underlying CHH

SARS-CoV-2 prolonged infection during advanced HIV disease evolves extensive immune escape

Characterizing SARS-CoV-2 evolution in specific geographies may help predict properties of the variants that come from these regions. We mapped neutralization of a SARS-CoV-2 strain that evolved over 6 months from ancestral virus in a person with advanced HIV disease in South Africa; this person was infected prior to emergence of the Beta and Delta variants. We longitudinally tracked the evolved virus and tested it against self-plasma and convalescent plasma from ancestral, Beta, and Delta infections. Early virus was similar to ancestral, but it evolved a multitude of mutations found in Omicron and other variants. It showed substantial but incomplete Pfizer BNT162b2 escape, weak neutralization by self-plasma, and despite pre-dating Delta, it also showed extensive escape of Delta infection-elicited neutralization. This example is consistent with the notion that SARS-CoV-2 evolving in individual immune-compromised hosts, including those with advanced HIV disease, may gain immune escape of vaccines and enhanced escape of Delta immunity, and this has implications for vaccine breakthrough and reinfections