A Josephson Parametric Oscillator-Based Ising Machine

Ising machines have emerged as a promising solution for rapidly solving NP-complete combinatorial optimization problems, surpassing the capabilities of traditional computing methods. By efficiently determining the ground state of the Hamiltonian during the annealing process, Ising machines can effectively complement CPUs in tackling optimization challenges. To realize these Ising machines, a bi-stable oscillator is essential to emulate the atomic spins and interactions of the Ising model. This study introduces a Josephson parametric oscillator (JPO)-based tile structure, serving as a fundamental unit for scalable superconductor-based Ising machines. Leveraging the bi-stable nature of JPOs, which are superconductor-based oscillators, the proposed machine can operate at frequencies of 7.5GHz while consuming significantly less power (by three orders of magnitude) than CMOS-based systems. Furthermore, the compatibility of the proposed tile structure with the Lechner-Hauke-Zoller (LHZ) architecture ensures its viability for large-scale integration. We conducted simulations of the tile in a noisy environment to validate its functionality. We verified its operational characteristics by comparing the results with the analytical solution of its Hamiltonian model. This verification demonstrates the feasibility and effectiveness of the JPO-based tile in implementing Ising machines, opening new avenues for efficient and scalable combinatorial optimization in quantum computing.Comment: 9 pages, 10 figures, 31 references. Accepted by PR

Unsupervised SFQ-Based Spiking Neural Network

Single Flux Quantum (SFQ) technology represents a groundbreaking advancement in computational efficiency and ultra-high-speed neuromorphic processing. The key features of SFQ technology, particularly data representation, transmission, and processing through SFQ pulses, closely mirror fundamental aspects of biological neural structures. Consequently, SFQ-based circuits emerge as an ideal candidate for realizing Spiking Neural Networks (SNNs). This study presents a proof-of-concept demonstration of an SFQ-based SNN architecture, showcasing its capacity for ultra-fast switching at remarkably low energy consumption per output activity. Notably, our work introduces innovative approaches: (i) We introduce a novel spike-timing-dependent plasticity mechanism to update synapses and to trace spike-activity by incorporating a leaky non-destructive readout circuit. (ii) We propose a novel method to dynamically regulate the threshold behavior of leaky integrate and fire superconductor neurons, enhancing the adaptability of our SNN architecture. (iii) Our research incorporates a novel winner-take-all mechanism, aligning with practical strategies for SNN development and enabling effective decision-making processes. The effectiveness of these proposed structural enhancements is evaluated by integrating high-level models into the BindsNET framework. By leveraging BindsNET, we model the online training of an SNN, integrating the novel structures into the learning process. To ensure the robustness and functionality of our circuits, we employ JoSIM for circuit parameter extraction and functional verification through simulation

Urine and milk iodine concentrations in healthy and congenitally hypothyroid neonates and their mothers

Wstęp: Częste występowanie wrodzonej niedoczynności tarczycy (CH, congenital hypothyroidism) w Iranie skłoniło autorów do oceny roli jodu w etiologii CH, opierając się na porównaniu jego stężenia w moczu zdrowych noworodków i noworodków z wrodzoną niedoczynnością tarczycy oraz w mleku i moczu ich matek. Materiał i metody: W tym przekrojowym badaniu zmierzono stężenie jodu w moczu (UIC, urinary iodine concentration) noworodków z CH oraz UIC i stężenie jodu w mleku (MIC, milk iodine concentration) ich matek, a następnie porównano je z wynikami otrzymanymi w grupie kontrolnej. Wartości UIC zmierzone u noworodków i karmiących matek podzielono na 3 kategorie: niskie UIC < 150 mg/l, średnie - 150-230 mg/l i wysokie > 230 mg/l. Analogiczne kategorie przyjęto dla MIC: niskie 180 mg/l. Wyniki: Mediana UIC u noworodków z CH (n = 68) i u zdrowych noworodków (n = 179) wynosiła odpowiednio 300,5 i 290,5 mg/dl, (P > 0,05). Mediana UIC w grupach badanej i kontrolnej wynosiła odpowiednio 150 i 130 mg/l (P > 0,05). Mediana MIC w grupie badanej była większa niż w grupie kontrolnej (210 mg/l v. 170 mg/l, P < 0,05). Stwierdzono dodatnią korelację między UIC u noworodków i MIC u ich matek. Nie wykazano wyraźnej zależności między UIC i stężeniem TSH w surowicy u noworodków oraz UIC I MIC u matek. Wnioski: Spożycie sodu w badanej populacji było prawidłowe. Nadmierna podaż sodu może być czynnikiem ryzyka CH, jednak w badaniu wykazano brak korelacji między MIC I UIC u matek i podobne wartości mediany UIC u noworodków w obu grupach, dlatego do sformułowania jednoznacznych wniosków potrzebne są dalsze badania. (Endokrynol Pol 2010; 61 (4): 371-376)Introduction: In view of the high prevalence of Congenital Hypothyroidism (CH) in Iran, in this study we evaluated the role of iodine in the aetiology of CH by comparing urine and milk iodine concentrations in healthy and congenitally hypothyroid neonates and their mothers. Material and methods: In a cross-sectional study, urinary iodine concentrations (UIC) in newborns with CH, as well as UIC and the milk iodine concentrations (MIC) of their mothers, were measured and compared with a control group. The lower, mid, and upper range of UIC for neonates and lactating mothers was considered to be 230 mg/L, and lower, mid, and upper range of MIC was considered to be 180 mg/L, respectively. Results: The median UICs in subjects with CH (n = 68) and healthy subjects (n = 179) were 300.5 and 290.5 mg/L, respectively (P > 0.05). The median UICs in the case and control groups were 150 and 130 mg/L, respectively (P > 0.05). The median MIC in the case group was higher than in the control group (210 mg/L v. 170 mg/L, P < 0.05).There was a positive correlation between newborn UIC and MIC. There was no significant correlation between newborn UIC and serum TSH, maternal UIC and maternal MIC, or newborn UIC and serum TSH. Conclusions: There is no inadequacy in iodine intake in the studied population. Iodine excess could be a possible risk factor for CH, but there were findings, such as lack of correlation between maternal MIC and UIC, and the median neonatal UIC, which was similar in the two groups, so, drawing conclusions should be done with some caution and requires further studies. (Pol J Endocrinol 2010; 61 (4): 371-376

Kinetics of Intrahepatic Hepatitis C Virus (HCV)-Specific CD4+ T Cell Responses in HCV and Schistosoma mansoni Coinfection: Relation to Progression of Liver Fibrosis

The kinetics of intrahepatic hepatitis C virus (HCV)-specific CD4+ T cell responses and their role in progression of fibrosis have not previously been characterized. Subjects with HCV/Schistosoma mansoni coinfection have a more rapid progression of HCV liver fibrosis than do those with HCV infection alone. The present prospective longitudinal study compared the liver histology, HCV-specific intrahepatic and peripheral CD4+ T cell proliferative responses, and cytokines (enzyme-linked immunospot) in 48 subjects with unresolved acute HCV infection with or without S. mansoni coinfection, at 6-10 months after acute infection and at the end of follow-up ( months), and the findings were correlated 96±8.7 to the rate of progression of fibrosis per year. Coinfected subjects had significant worsening of fibrosis, compared with subjects with HCV infection alone. At baseline, subjects with HCV infection alone had stronger multispecific intrahepatic HCV-specific CD4+ T helper 1 responses than did coinfected subjects, who had either no responses or weak, narrowly focused responses, and, over time, these T cell responses were maintained only in the liver. The rate of progression of fibrosis and virus load inversely correlated with intrahepatic HCV-specific CD4+ T cell response. The present prospective analysis indicates that enhancement of progression of liver fibrosis is associated with failure to develop early, multispecific, HCV-specific CD4+ Th1 responses, suggesting that novel therapeutic approaches inducing strong cellular immune responses might limit subsequent liver damage in individuals with chronic hepatitis

Discovery and validation of small-molecule heat-shock protein 90 inhibitors through multimodality molecular imaging in living subjects

Up-regulation of the folding machinery of the heat-shock protein 90 (Hsp90) chaperone protein is crucial for cancer progression. The two Hsp90 isoforms (α and β) play different roles in response to chemotherapy. To identify isoform-selective inhibitors of Hsp90(α/β)/cochaperone p23 interactions, we developed a dual-luciferase (Renilla and Firefly) reporter system for high-throughput screening (HTS) and monitoring the efficacy of Hsp90 inhibitors in cell culture and live mice. HTS of a 30,176 small-molecule chemical library in cell culture identified a compound, N-(5-methylisoxazol-3-yl)-2-[4-(thiophen-2-yl)-6-(trifluoromethyl)pyrimidin-2-ylthio]acetamide (CP9), that binds to Hsp90(α/β) and displays characteristics of Hsp90 inhibitors, i.e., degradation of Hsp90 client proteins and inhibition of cell proliferation, glucose metabolism, and thymidine kinase activity, in multiple cancer cell lines. The efficacy of CP9 in disrupting Hsp90(α/β)/p23 interactions and cell proliferation in tumor xenografts was evaluated by non-invasive, repetitive Renilla luciferase and Firefly luciferase imaging, respectively. At 38 h posttreatment (80 mg/kg × 3, i.p.), CP9 led to selective disruption of Hsp90α/p23 as compared with Hsp90β/p23 interactions. Small-animal PET/CT in the same cohort of mice showed that CP9 treatment (43 h) led to a 40% decrease in 18F-fluorodeoxyglucose uptake in tumors relative to carrier control-treated mice. However, CP9 did not lead to significant degradation of Hsp90 client proteins in tumors. We performed a structural activity relationship study with 62 analogs of CP9 and identified A17 as the lead compound that outperformed CP9 in inhibiting Hsp90(α/β)/p23 interactions in cell culture. Our efforts demonstrated the power of coupling of HTS with multimodality molecular imaging and led to identification of Hsp90 inhibitors

Crosstalks between Myo-Inositol Metabolism, Programmed Cell Death and Basal Immunity in Arabidopsis

BACKGROUND: Although it is a crucial cellular process required for both normal development and to face stress conditions, the control of programmed cell death in plants is not fully understood. We previously reported the isolation of ATXR5 and ATXR6, two PCNA-binding proteins that could be involved in the regulation of cell cycle or cell death. A yeast two-hybrid screen using ATXR5 as bait captured AtIPS1, an enzyme which catalyses the committed step of myo-inositol (MI) biosynthesis. atips1 mutants form spontaneous lesions on leaves, raising the possibility that MI metabolism may play a role in the control of PCD in plants. In this work, we have characterised atips1 mutants to gain insight regarding the role of MI in PCD regulation. METHODOLOGY/PRINCIPAL FINDINGS: - lesion formation in atips1 mutants depends of light intensity, is due to PCD as evidenced by TUNEL labelling of nuclei, and is regulated by phytohormones such as salicylic acid - MI and galactinol are the only metabolites whose accumulation is significantly reduced in the mutant, and supplementation of the mutant with these compounds is sufficient to prevent PCD - the transcriptome profile of the mutant is extremely similar to that of lesion mimic mutants such as cpr5, or wild-type plants infected with pathogens. CONCLUSION/SIGNIFICANCE: Taken together, our results provide strong evidence for the role of MI or MI derivatives in the regulation of PCD. Interestingly, there are three isoforms of IPS in Arabidopsis, but AtIPS1 is the only one harbouring a nuclear localisation sequence, suggesting that nuclear pools of MI may play a specific role in PCD regulation and opening new research prospects regarding the role of MI in the prevention of tumorigenesis. Nevertheless, the significance of the interaction between AtIPS1 and ATXR5 remains to be established

Elective cancer surgery in COVID-19-free surgical pathways during the SARS-CoV-2 pandemic: An international, multicenter, comparative cohort study

PURPOSE As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19–free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19–free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19–free surgical pathways. Patients who underwent surgery within COVID-19–free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19–free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score–matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19–free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION Within available resources, dedicated COVID-19–free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

Elective Cancer Surgery in COVID-19-Free Surgical Pathways During the SARS-CoV-2 Pandemic: An International, Multicenter, Comparative Cohort Study.

PURPOSE: As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19-free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS: This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19-free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS: Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19-free surgical pathways. Patients who underwent surgery within COVID-19-free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19-free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score-matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19-free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION: Within available resources, dedicated COVID-19-free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks