Search Results (14,633)

N-Glycolylneuraminic acid (Neu5Gc) is a sialic acid variant commonly found in most mammals but not synthesized by humans due to an inactivating mutation in the CMP-Neu5Ac hydroxylase (CMAH) gene. Despite this, Neu5Gc-containing molecules are consistently detected in human tissues, particularly in malignant tumors. However, the mechanisms underlying Neu5Gc accumulation and its role in cancer development remain poorly understood. Objectives: This review aims to analyze clinical and experimental evidence regarding the presence of Neu5Gc-containing glycoconjugates in both tumor and non-tumor human tissues, exploring potential mechanisms of the Neu5Gc expression and evaluating its contribution to tumor biology, with a particular focus on the Neu5Gc-GM3 ganglioside. Methods: A comprehensive review of the literature was conducted, integrating findings from immunohistochemistry, chromatography, and molecular studies to assess the expression and implications of Neu5Gc in cancer biology. Results: Neu5Gc-containing glycoconjugates were found to preferentially accumulate in various malignant tumors, while their presence in normal tissues was restricted to cells with high turnover rates. This accumulation is potentially mediated by dietary uptake, hypoxic conditions, and metabolic alterations in cancer cells. Additionally, Neu5Gc-containing molecules were associated with the activation of oncogenic pathways. Conclusion: Neu5Gc-containing glycoconjugates play a multifaceted role in cancer progression and present potential as prognostic markers and therapeutic targets. Full article

Background/Objectives: To evaluate the effectiveness of curative (chemo)radiotherapy in patients with hypopharyngeal carcinoma and to identify prognostic factors influencing treatment outcomes. Methods: We conducted a retrospective study of 173 consecutive patients, treated with definitive or postoperative (chemo)radiotherapy from 2002 to 2020 [median age 60 years; current/former smokers 95%; UICC stage III/IV 96%]. Radiation therapy was preceded by a radical resection of a primary tumor in 32% of patients. One hundred patients received chemotherapy. Results: The median total dose of radiotherapy achieved was 70 Gy. The five- and ten-year locoregional controls were 63%, and the five- and ten-year distant controls were 77% and 76%, respectively. The five- and ten-year overall survival rates were 24% and 9%, respectively. Conclusions: The results demonstrate the limited effectiveness of curative (chemo)radiotherapy in patients with hypopharyngeal carcinoma with long-term locoregional and distant control of half of the treated patients. The multivariate analysis indicated that initial surgery, chemotherapy, comorbidity score (as assessed by ACE-27), pretreatment tracheostomy, hemoglobin level and initial response to treatment were the strongest prognostic factors in predicting survival. Using these factors, corresponding predictive models were constructed. Full article

In this study, an innovative switching approach is explored to improve the reliability of 1 Selector-1 ReRAM (1S1R) devices, integrated into a 4K crossbar array (CBA). The key innovation is the use of DC sweeping for set operations and AC single-pulse resetting to minimize device stress and prevent breakdown. The selector, based on a GeSeTe ovonic threshold switching (OTS) element, demonstrated excellent endurance (>10¹² cycles), fast switching (<100 ns), and high device-to-device uniformity (<5% variability). The ReRAM, constructed with Pt/LiNbO_x/W, exhibited robust bipolar resistive switching, multi-bit capability, and endurance exceeding 10¹² cycles. The integrated 1S1R CBA demonstrated reliable retention and low variability in operation, showing potential for high-performance, high-density memory applications. Full article

To achieve sustainable extractions, this study examines the impact of different extraction methods to utilize waste from the sugar industry. In addition to conventional thermal extraction, the impact of high-power ultrasound (US) and high-voltage electrical discharge (HVED)-assisted extractions on the yield of bioactive compounds and the antioxidant capacity (AC) value of sugar beet leaf extracts was determined. US extraction proved to be an excellent method for extracting bioactive compounds, while HVED extraction proved to be an excellent method for extracting Vitexin. AC was measured both spectrophotometrically (DPPH and FRAP) and spectroscopically via electron spin resonance (ESR). The AC results correlate with each other, and the highest AC values were found in the US-treated samples with 25% ethanol solution as the extraction solvent. Characterization of the plasma via optical emission spectroscopy (OES) showed that neither the solvent nor the sample influenced the plasma spectra, only the gas used (nitrogen/argon). All of the obtained results provide an excellent basis for future research into the utilization of food waste and by-products. Full article

This paper presents the latest advancements in model predictive control (MPC) for grid-connected power inverters in renewable energy applications. It focuses on grid-connected PV systems employing MPC techniques. Two main categories of MPC are introduced: continuous control MPC (CC MPC) and predetermined control MPC (PC MPC). In CC MPC, a modulator is required to generate the control signal, whereas in PC MPC, the MPC controller directly performs the control process and generates the control pulses. Consequently, PC MPC is preferred for most power converter applications due to its lower computational complexity and simpler implementation. However, ensuring a fixed switching frequency remains a significant challenge when using this control strategy for power electronic converters. Moreover, the computation requirements of MPC strategies are challenging, due to the large number of online calculations. Even with the significant improvements in DSPs, computation complexity is still a continuing issue, especially for applications requiring a high frequency. This paper also examines the design considerations for both types of MPC in PV applications. Lastly, it reviews recent developments in grid-connected inverters utilizing MPC strategies, with a focus on system stability, converter topology, and control objectives. Full article

Background: Amlodipine has recently been incidentally reported with angioedema and is frequently prescribed with renin–angiotensin–aldosterone system inhibitors (RAAS-i) for hypertension management. While RAAS-i drugs are known to cause angioedema, the risk associated with amlodipine alone or in combination with RAAS-i drugs remains unclear. This study aimed to evaluate the association between amlodipine use and angioedema using pharmacovigilance data. Methods: We analyzed adverse event reports from the US FDA Adverse Event Reporting System using both frequentist and Bayesian approaches. Drug–drug interactions were assessed using multiplicative models. Additionally, we conducted a systematic review of published case reports of amlodipine-associated angioedema. Results: Among 29,661,136 reports, 2076 cases of angioedema were identified (1067 with amlodipine alone, 1009 with amlodipine–RAAS-i combinations). Significant safety signals were detected for amlodipine alone and in combination with aliskiren, specific ACE inhibitors (quinapril, benazepril, trandolapril, fosinopril, perindopril), and certain ARBs (candesartan, losartan). No significant interactions were observed between amlodipine and RAAS-i drugs except for the amlodipine–trandolapril combination. A review of published cases demonstrated definite causality in two cases and possible association in others, with most patients presenting with oropharyngeal/facial edema and achieving complete recovery following drug discontinuation and standard therapy. Conclusions: Our findings suggest a potentially increased risk of angioedema with amlodipine, both as monotherapy and in specific RAAS-i combinations. While these results should not discourage appropriate clinical use, they emphasize the importance of monitoring for angioedema, particularly during therapy initiation. The findings from this study need to be validated in prospective studies for further elucidation of the underlying mechanisms. Full article

This study proposes a high-frequency Pulse Amplitude-Modulation Temporal-Interference (PAM-TI) current stimulation device, which utilizes two sets of Amplitude-modulated transcranial alternating current stimulation (AM-tACS): one AM frequency at f0 (where f0 = 2 kHz) (source 1) and the other AM frequency at f1 = f0 + △f (where f1 = 2.01 kHz) (source 2), to generate a △f (where △f = 10 Hz) envelope modulated at a fc (where fc = 100 kHz) high carrier frequency. The high carrier frequency reduces body impedance and conserves more stimulation power, allowing it to penetrate the skin and reach the subcutaneous region. The proposed PAM-TI technique elevates the two current sources to a 100 kHz carrier frequency. Instead of the challenges associated with generating high-frequency stimulation currents using an MCU and DAC, the proposed PAM-TI stimulation device achieves this by simply utilizing a pair of complementary pulse-width modulations (PWMs). The push–pull technique is employed to balance the charging currents between the anode and cathode, synchronizing the current timing of Source 1 and Source 2 under the fc modulation condition. To minimize signal attenuation, the PAM circuit is integrated directly into the electrode, ensuring the high-frequency signal is generated close to the body and preventing degradation from long wires. Additionally, a dry pin-type spring-loaded electrode is used to reduce interference caused by hair when placed on the head. The device’s validity and current directionality were verified using a scalp tissue-mimicking phantom composed of agar and saline. Full article

A growing body of experimental and computational studies suggests that the cross-neutralization antibody activity against Omicron variants may be driven by the balance and tradeoff between multiple energetic factors and interaction contributions of the evolving escape hotspots involved in antigenic drift and convergent evolution. However, the dynamic and energetic details quantifying the balance and contribution of these factors, particularly the balancing nature of specific interactions formed by antibodies with epitope residues, remain largely uncharacterized. In this study, we performed molecular dynamics simulations, an ensemble-based deep mutational scanning of SARS-CoV-2 spike residues, and binding free energy computations for two distinct groups of broadly neutralizing antibodies: the E1 group (BD55-3152, BD55-3546, and BD5-5840) and the F3 group (BD55-3372, BD55-4637, and BD55-5514). Using these approaches, we examined the energetic determinants by which broadly potent antibodies can largely evade immune resistance. Our analysis revealed the emergence of a small number of immune escape positions for E1 group antibodies that correspond to the R346 and K444 positions in which the strong van der Waals and interactions act synchronously, leading to the large binding contribution. According to our results, the E1 and F3 groups of Abs effectively exploit binding hotspot clusters of hydrophobic sites that are critical for spike functions along with the selective complementary targeting of positively charged sites that are important for ACE2 binding. Together with targeting conserved epitopes, these groups of antibodies can lead expand the breadth and resilience of neutralization to the antigenic shifts associated with viral evolution. The results of this study and the energetic analysis demonstrate excellent qualitative agreement between the predicted binding hotspots and critical mutations with respect to the latest experiments on average antibody escape scores. We argue that the E1 and F3 groups of antibodies targeting binding epitopes may leverage strong hydrophobic interactions with the binding epitope hotspots that are critical for the spike stability and ACE2 binding, while escape mutations tend to emerge in sites associated with synergistically strong hydrophobic and electrostatic interactions. Full article

Canonical transient receptor potential (TRPC) channels contribute to calcium homeostasis, which is involved in penile vascular contractility and erectile dysfunction (ED) pathophysiology. We evaluated the impact of TRPC5 inhibition on endothelial function in penile vascular tissue from aging rats and ED patients and its effect on the relaxant efficacy of PDE5 inhibitors. TRPC inhibitor-induced endothelial and neurogenic relaxations were evaluated in corpus cavernosum (RCC) from a rat model of aging-related ED and in human penile resistance arteries (HPRAs) and corpus cavernosum (HCC) from ED patients and organ donors (NoED). The TRPC5 inhibitor, AC1903, was more effective than TRPC3 and TRPC4 inhibitors in relaxing aged RCC and HCC and HPRA from ED patients. In addition to enhancing endothelial and neurogenic relaxations in RCC from aged animals, AC1903 improved endothelium-dependent relaxation in both HCC and HPRA from ED patients but not in tissues from NoED. Cavernosal expression of TRPC5 was not different between ED and NoED subjects. AC1903 potentiated relaxations to the PDE5 inhibitor, tadalafil, in HCC/HPRA from ED patients. TRPC5 inhibition improved penile vascular function in aged rats and patients with ED. TRPC5 inhibition could be a potential therapeutic target for ED, particularly when combined with PDE5 inhibitors to enhance treatment outcomes. Full article

Residential water heating represents one of the most energy-intensive household applications, particularly in South Africa, where immersed resistive element heating dominates. Solar photovoltaic systems provide a promising solution for augmenting grid-based electrical water heaters, offering energy cost savings and environmental benefits. This study evaluates a novel approach to integrate solar photovoltaic directly into electrical water heater systems without using inverters. Using a combination of field experiments and simulation, four heating strategies were assessed, namely: “grid only”, “solar medium”, “solar heavy”, and “solar timer”. Metrics such as solar augmentation ratio, solar utilization, and cold event frequency were analyzed for different seasons using real-world and simulated water usage profiles. Results demonstrate significant grid energy reductions through solar augmentation, particularly in warmer seasons. However, the effectiveness of the strategies varies, with increased solar utilization often correlated with a higher frequency of cold events. A hybrid seasonal strategy is proposed to optimize energy savings while maintaining user comfort. This work highlights the potential of direct DC solar photovoltaic integration as a cost-effective and sustainable enhancement for residential water heating. Full article

Carbon steel structures employed to convey hydrocarbons and other dangerous fluids, such as oil or flammable liquids, are equipped with degradation prevention systems, which typically consist of a cathodic protection (CP) system combined with an external insulating coating, both designed to reduce the corrosion rate below 10 µm/year. The presence of electrical interference, both AC and DC, can cause significant corrosion damage to metallic structures, even when CP is applied. DC interference is determined by the presence of a third-party CP system or public transportation system. AC interference may occur through conduction or induction mechanisms, caused by high-voltage powerlines or high-speed trains, powered by AC. Both interferences may lead to localized corrosion at coating defects, despite compliance with the −0.850 V saturated Cu/CuSO₄ reference electrode (CSE) protection criterion. Considering AC-induced corrosion, both field failures and laboratory investigations have demonstrated that corrosion can occur at industrial frequencies, and when CP is applied following the standards. Even though AC-induced degradation is generally not as severe as DC interference, uncertainties remain regarding the protection potential range necessary to achieve acceptable corrosion prevention under AC interference. To formulate a CP criterion under AC interference, weight loss measurements were conducted on carbon steel samples under cathodic protection in solutions that simulate real soil conditions. Carbon steel coupons protected by CP were interfered with AC densities ranging from 1 A/m² to 800 A/m² for four months. During this time interval, polarization potential, protection current density and AC density were monitored. Based on the experimental data gathered during this study, a proposal for a risk map is also suggested. The results indicate that overprotection (potentials < −1.2 V CSE) represents the most dangerous scenario when AC interference is involved. Full article

The increasing demand for electricity and the imperatives of climate change have made the optimization of power system planning critical for the energy transition and grid efficiency. This study presents an innovative planning method for inter-regional AC-DC hybrid power systems, leveraging the Classification and Regression Tree (CART) algorithm to optimize the operational characteristics of direct current (DC) channels. By designing a closed-loop iteration, precise operational constraints are considered by the CART algorithm, which immerged into the planning model to achieve safe and economic optimization. Based on the empirical analysis of the HRP-38 system, this study concludes that the CART algorithm offers a constructive approach to managing the operational complexities of modern power grids. By optimizing and refining DC operational characteristics based on actual system requirements, the algorithm contributes to improvements in safety, economic efficiency, and environmental sustainability within the confines of the HRP-38 node system. Consequently, the effectiveness of the CART optimization approach could be corroborated. Meanwhile, this study also acknowledges the limitations in generalizing these results to other power grid configurations and the need for further exploration in developing environmentally conscious planning methods. Full article

Background/Objectives: This work introduces accuracy- and precision-ROC curves in addition to SS– and PV–ROC curves and shows a novel means of profiling biomarker characteristics for validation of optimal cutoffs in clinical diagnostics and decision making. Methods: This investigation included 91 patients with a confirmed bladder cancer diagnosis and 1152 patients without evidence of cancer. The study performed a quantitative investigation of used-up test cassettes from the visual UBC^® Rapid qualitative point-of-care assay, which had already been applied in routine diagnostics. Using a photometric reader, quantitative data could also be obtained from the test line of the used cassettes. The ROC curves were constructed using different thresholds or cutoff levels to determine the TP/TN and FP/FN values for each threshold at concentrations of 5, 10, 30, 50, 90, 110, 250 and 300 µg/L. The resulting TP/TN and FP/FN values were used to calculate the sensitivity/specificity, accuracy, precision and predictive values in order to plot the ROC curves with integrated cutoff value distributions and their index cutoff diagrams. Results: A common, optimal cutoff value for all the diagnostic parameters was derived with the aid of an ROC index cutoff diagram. It includes higher specificity and an acceptable number of NPVs. As a result, use of a sensitivity–specificity ROC curve and the Youden index only permits the selection of a maximal threshold value or cutoff point for the biomarker of interest but disregards the clinical status of the patient, whereas the precision, accuracy and predictive values give information related to the disease. Conclusions: This work’s novelty compared to the existing methodology includes the first international publication of accuracy- and precision-ROC curves. It enables the investigation of the relationship among the sensitivity, specificity, precision, accuracy and predictive values at varied cutoff levels within a bioassay, presenting these in a single graph consisting of selected receiver operating characteristic (ROC) curves for each parameter, including cutoff distribution curves. This is a transparent method to identify appropriate cutoffs for multiple diagnostic parameters. According to the results, the single-sided use of a sensitivity–specificity ROC curve including the maximal Youden index value as an optimal cutoff or single-point determinations for predictive values cannot provide diagnostic information of the same quality as that given by a multi-parameter diagnostic profile and a multi-parameter cutoff-index-diagram-derived optimal value as presented within this work. The proposed multi-parameter cutoff-index diagram includes novel index cutoff AOX. It is a new different method that allows a quantitative comparison of the results from multi-parameter ROC curves, which cannot be performed with the AUC. However, the methods are different and do not exclude each other. Full article

This review paper describes and compares the practical methods that make it possible to calculate an average value of apparent, active, and reactive (i.e., blind and distorted) power in each calculation step. In addition to two methods, p –q and ip –iq, it deals with the application of the id –iq method for determining power components' mean values in a discrete step. The results are important and needed for the right dimensioning and sizing of power electronic and electrical systems (PEESs), which those power components produce. This is because the integral calculation for the mean values of the product of voltage u(t) and current i(t) always gives a value lower than the actual value of the apparent power. Using moving average and moving root mean square (rms) techniques (or digital filtering), one obtains the right values, although with a time delay. Using sliding filtering, these techniques calculate the average or rms values, respectively, of the power components in each step k. By calculating the moving average value of the power components in both transient and steady states (on/off as well), we achieve the correct design of the system. The transients for the three- and single-phase power electronic systems are modeled, simulated, and theoretically supported in this study. Any PEES can be determined and sized using the calculated data. The real-time HW simulator Plecs RT Box 1 and Matlab/Simulink 2024a simulations validate the comprehensive time waveform produced by the suggested method. Full article

The study discloses the application of transformer-based deep learning models for the task of super-enhancers prediction in human tumor cell lines with a specific focus on sequence-only features within studied entities of super-enhancer and enhancer elements in the human genome. The proposed SE-prediction method included the GENA-LM application at handling long DNA sequences with the classification task, distinguishing super-enhancers from enhancers using H3K36me, H3K4me1, H3K4me3 and H3K27ac landscape datasets from HeLa, HEK293, H2171, Jurkat, K562, MM1S and U87 cell lines. The model was fine-tuned on relevant sequence data, allowing for the analysis of extended genomic sequences without the need for epigenetic markers as proposed in early approaches. The study achieved balanced accuracy metrics, surpassing previous models like SENet, particularly in HEK293 and K562 cell lines. Also, it was shown that super-enhancers frequently co-localize with epigenetic marks such as H3K4me3 and H3K27ac. Therefore, the attention mechanism of the model provided insights into the sequence features contributing to SE classification, indicating a correlation between sequence-only features and mentioned epigenetic landscapes. These findings support the potential transformer models use in further genomic sequence analysis for bioinformatics applications in enhancer/super-enhancer characterization and gene regulation studies. Full article