Accelerating 3-D GPU-based Motion Tracking for Ultrasound Strain Elastography Using Sum-Tables: Analysis and Initial Results.

Now, with the availability of 3-D ultrasound data, a lot of research efforts are being devoted to developing 3-D ultrasound strain elastography (USE) systems. Because 3-D motion tracking, a core component in any 3-D USE system, is computationally intensive, a lot of efforts are under way to accelerate 3-D motion tracking. In the literature, the concept of Sum-Table has been used in a serial computing environment to reduce the burden of computing signal correlation, which is the single most computationally intensive component in 3-D motion tracking. In this study, parallel programming using graphics processing units (GPU) is used in conjunction with the concept of Sum-Table to improve the computational efficiency of 3-D motion tracking. To our knowledge, sum-tables have not been used in a GPU environment for 3-D motion tracking. Our main objective here is to investigate the feasibility of using sum-table-based normalized correlation coefficient (ST-NCC) method for the above-mentioned GPU-accelerated 3-D USE. More specifically, two different implementations of ST-NCC methods proposed by Lewis et al. and Luo-Konofagou are compared against each other. During the performance comparison, the conventional method for calculating the normalized correlation coefficient (NCC) was used as the baseline. All three methods were implemented using compute unified device architecture (CUDA; Version 9.0, Nvidia Inc., CA, USA) and tested on a professional GeForce GTX TITAN X card (Nvidia Inc., CA, USA). Using 3-D ultrasound data acquired during a tissue-mimicking phantom experiment, both displacement tracking accuracy and computational efficiency were evaluated for the above-mentioned three different methods. Based on data investigated, we found that under the GPU platform, Lou-Konofaguo method can still improve the computational efficiency (17-46%), as compared to the classic NCC method implemented into the same GPU platform. However, the Lewis method does not improve the computational efficiency in some configuration or improves the computational efficiency at a lower rate (7-23%) under the GPU parallel computing environment. Comparable displacement tracking accuracy was obtained by both methods

p97 Negatively Regulates NRF2 by Extracting Ubiquitylated NRF2 from the KEAP1-CUL3 E3 Complex

Activation of the stress-responsive transcription factor NRF2 is the major line of defense to combat oxidative or electrophilic insults. Under basal conditions, NRF2 is continuously ubiquitylated by the KEAP1-CUL3-RBX1 E3 ubiquitin ligase complex and is targeted to the proteasome for degradation (the canonical mechanism). However, the path from the CUL3 complex to ultimate proteasomal degradation was previously unknown. p97 is a ubiquitin-targeted ATP-dependent segregase that extracts ubiquitylated client proteins from membranes, protein complexes, or chromatin and has an essential role in autophagy and the ubiquitin proteasome system (UPS). In this study, we show that p97 negatively regulates NRF2 through the canonical pathway by extracting ubiquitylated NRF2 from the KEAP1-CUL3 E3 complex, with the aid of the heterodimeric cofactor UFD1/NPL4 and the UBA-UBX-containing protein UBXN7, for efficient proteasomal degradation. Given the role of NRF2 in chemoresistance and the surging interest in p97 inhibitors to treat cancers, our results indicate that dual p97/NRF2 inhibitors may offer a more potent and long-term avenue of p97-targeted treatment

Clinical research on RSV prevention in children and pregnant women: progress and perspectives

Respiratory syncytial virus (RSV) is a significant causative agent of bronchitis and pneumonia in infants and children. The identification and structural analysis of the surface fusion glycoprotein of RSV represents a pivotal advancement in the development of RSV prevention. This review provides a comprehensive summary of RSV monoclonal antibody (mAb) and vaccine clinical trials registered on ClinicalTrials.gov, emphasizing on the classification, name, target, phase, clinical outcomes, and safety data of RSV vaccination in newborns, infants and children. We also discuss the characteristics of the types of RSV vaccines for maternal immunity and summarize the current clinical research progress of RSV vaccination in pregnant women and their protective efficacy in infants. This review will provide new ideas for the development of RSV prevention for children in the future

Ultrasmall Glutathione-Protected Gold Nanoclusters as Next Generation Radiotherapy Sensitizers with High Tumor Uptake and High Renal Clearance

Radiotherapy is often the most straightforward first line cancer treatment for solid tumors. While it is highly effective against tumors, there is also collateral damage to healthy proximal tissues especially with high doses. The use of radiosensitizers is an effective way to boost the killing efficacy of radiotherapy against the tumor while drastically limiting the received dose and reducing the possible damage to normal tissues. Here, we report the design and application of a good radiosensitizer by using ultrasmall gold nanoclusters with a naturally occurring peptide (e.g., glutathione or GSH) as the protecting shell. The GSH coated gold nanoclusters can escape the RES absorption, leading to a good tumor uptake (8.1% ID/g at 24 h post injection). As a result, the as-designed Au nanoclusters led to a strong enhancement for radiotherapy, as well as a negligible damage to normal tissues. After the treatment, the ultrasmall gold nanoclusters can be efficiently cleared by the kidney, thereby avoiding potential long term side effects caused by the accumulation of gold atoms in the body. Our data suggest that the ultrasmall peptide protected Au nanoclusters are a promising radiosensitizer for cancer radiotherapy.Comment: 15 Pages, 6 Figures, Scientific Reports 5, 201

Association of objective and subjective parameters of obstructive sleep apnea with plasma aldosterone concentration in 2,066 hypertensive and 25,368 general population

Study objectivesObstructive sleep apnea (OSA) severity has been suggested in aldosterone elevation in resistant hypertension, whereas it is undetermined in the rest population. We explored the association of OSA parameters with plasma aldosterone concentration (PAC) in participants with and without hypertension.MethodsWe enrolled clinically hypertensive patients with polysomnography and PAC data under no interfering agents, compared (log) PAC, and assessed the linearity of log PAC by tertiles (T1/2/3) of sleep parameters and their association using linear regression by gender and age. We enrolled participants with and without hypertension who had No-SAS scale and PAC data from the community and duplicated the observations from clinical setting considering age, gender, and presence of hypertension.ResultsOf the 2,066 clinical patients with hypertension (1,546 with OSA), men participants (n=1,412), log apnea–hypopnea index (p=0.043), apnea index (AI, p=0.010), and lowest oxygen saturation (LSaO2, p=0.013) showed significant linearity with log PAC. Log AI (B=0.04, 95%CI: 0.01,0.07, p=0.022) and log LSaO2 (B=−0.39, 95%CI: −0.78,−0.01, p=0.044) showed significant positive and negative linear associations with log PAC in regression. In community dwellers, 6,417 participants with untreated hypertension (2,642 with OSA) and 18,951 normotensive participants (3,000 with OSA) were included. Of the men participants with and without hypertension, the OSA group showed significantly higher (log) PAC than did their counterparts, and log No-SAS score showed positive association with log PAC (hypertension: B=0.072, 95%CI: 0.002,0.142, p=0.043; normotension: B=0.103, 95%CI: 0.067,0.139, p<0.001) in linear regression analysis, which were consistent in all age groups.ConclusionsOSA parameters were positively associated with PAC in normotensive and hypertensive participants, indicating that OSA may increase circulating aldosterone, especially in men

Breast-cancer-secreted miR-122 reprograms glucose metabolism in premetastatic niche to promote metastasis

Reprogrammed glucose metabolism as a result of increased glycolysis and glucose uptake is a hallmark of cancer. Here we show that cancer cells can suppress glucose uptake by non-tumour cells in the pre-metastatic niche, by secreting vesicles that carry high levels of the miR-122 microRNA. High miR-122 levels in the circulation have been associated with metastasis in breast cancer patients and we show that cancer-cell-secreted miR-122 facilitates metastasis by increasing nutrient availability in the pre-metastatic niche. Mechanistically cancer-cell-derived miR-122 suppresses glucose uptake by niche cells in vitro and in vivo by downregulating the glycolytic enzyme pyruvate kinase (PKM). In vivo inhibition of miR-122 restores glucose uptake in distant organs, including brain and lungs, and decreases the incidence of metastasis. These results demonstrate that by modifying glucose utilization by recipient pre-metastatic niche cells, cancer-derived extracellular miR-122 is able to reprogram systemic energy metabolism to facilitate disease progression

Protein Phase Separation: New Insights into Carcinogenesis

Phase separation is now acknowledged as an essential biologic mechanism wherein distinct activated molecules assemble into a different phase from the surrounding constituents of a cell. Condensates formed by phase separation play an essential role in the life activities of various organisms under normal physiological conditions, including the advanced structure and regulation of chromatin, autophagic degradation of incorrectly folded or unneeded proteins, and regulation of the actin cytoskeleton. During malignant transformation, abnormally altered condensate assemblies are often associated with the abnormal activation of oncogenes or inactivation of tumor suppressors, resulting in the promotion of the carcinogenic process. Thus, understanding the role of phase separation in various biological evolutionary processes will provide new ideas for the development of drugs targeting specific condensates, which is expected to be an effective cancer therapy strategy. However, the relationship between phase separation and cancer has not been fully elucidated. In this review, we mainly summarize the main processes and characteristics of phase separation and the main methods for detecting phase separation. In addition, we summarize the cancer proteins and signaling pathways involved in phase separation and discuss their promising future applications in addressing the unmet clinical therapeutic needs of people with cancer. Finally, we explain the means of targeted phase separation and cancer treatment

Incoherency Problems in a Combination of Description Logics and Rules

A paraconsistent semantics has been presented for hybrid MKNF knowledge bases—a combination method for description logics and rules. However, it is invalid when incoherency occurs in the knowledge base. In this paper, we introduce a semi-S5 semantics for hybrid MKNF knowledge bases on the basis of nine-valued lattice, such that it is paraconsistent for incoherent knowledge base. It is shown that a semi-S5 model can be computed via a fixpoint operator and is in fact a paraconsistent MKNF model when the knowledge base is incoherent. Moreover, we apply six-valued lattice to hybrid MKNF knowledge bases and present a suspicious semantics to distinguish different trust level information. At last, we investigate the relationship between suspicious semantics and paraconsistent semantics