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IEEE 802.11ax uplink orthogonal frequency division multiple access (OFDMA)-based random access (UORA) is a new feature for random channel access in wireless local area networks (WLANs). Similar to the legacy random access scheme in WLANs, UORA performs the OFDMA backoff (OBO) procedure to access the channel and decides on a random OBO counter within the OFDMA contention window (OCW) value. An access point (AP) can determine the OCW range and inform each station (STA) of it. However, how to determine a reasonable OCW range is beyond the scope of the IEEE 802.11ax standard. The OCW range is crucial to the UORA performance, and it primarily depends on the number of contending STAs, but it is challenging for the AP to accurately and quickly estimate or keep track of the number of contending STAs without the aid of a specific signaling mechanism. In addition, the one for this purpose incurs an additional delay and overhead in the channel access procedure. Therefore, the performance of a UORA scheme can be degraded by an improper OCW range, especially when the number of contending STAs changes dynamically. We first observed the effect of OCW values on channel efficiency and derived its optimal value from an analytical model. Next, we proposed a simple yet effective OBO control scheme where each STA determines its own OBO counter in a distributed manner rather than adjusting the OCW value globally. In the proposed scheme, each STA determines an appropriate OBO counter depending on whether the previous transmission was successful or not so that collisions can be mitigated without leaving OFDMA resource units unnecessarily idle. The results of a simulation study confirm that the throughput of the proposed scheme is comparable to the optimal OCW-based scheme and is improved by up to 15 times compared to the standard UORA scheme.

Multi-link operation (MLO) is a new and essential mechanism of IEEE 802.11be Extremely High Throughput (Wi-Fi 7) that can increase throughput and decrease latency in Wireless Local Area Networks (WLANs). The MLO enables a Multi-Link Device (MLD) to perform Simultaneous Transmission and Reception (STR) in different frequency bands. However, not all MLDs can support STR due to cross-link or in-device coexistence interference, while an STR-unable MLD (NSTR-MLD) can transmit multiple frames simultaneously in more than two links. This study focuses on the problems when NSTR-MLDs share a link with Single-Link Devices (SLDs). We propose a Contention-Less Synchronous Transmission (CLST) mechanism to improve fairness between NSTR-MLDs and SLDs while increasing the total network throughput. The proposed mechanism classifies links as MLD Dominant Links (MDLs) and Heterogeneous Coexistence Links (HCLs). In the proposed mechanism, an NSTR-MLD obtains a Synchronous Transmission Token (STT) through a virtual channel contention in the HCL but does not actually transmit a frame in the HCL, which is compensated for by a synchronous transmission triggered in the MDL. Moreover, the CLST mechanism allows additional subsequent transmissions up to the accumulated STT without further contention. Extensive simulation results confirm the outstanding performance of the CLST mechanism in terms of total throughput and fairness compared to existing synchronous transmission mechanisms.

In this study, we address the problem of downlink throughput degradation in dense wireless local area networks (WLANs) based on the IEEE 802.11ax standard. We demonstrate that this problem essentially results from the asymmetric characteristic of carrier sense multiple access between downlink and uplink transmissions in infrastructure WLANs, and it is exacerbated by a dynamic sensitivity control algorithm that aims to improve spatial reuse (SR) in IEEE 802.11ax. To solve this problem, we propose the interference-aware two-level differentiation mechanism consisting of the dual channel access (DCA) and supplemental power control (SPC) schemes. The proposed mechanism introduces a new measure called a spatial reusability indicator, which roughly estimates the signal-to-interference ratio from the received signal strength of beacon frames. Based on this measure, stations (STAs) are classified into the following two categories: spatial reusable STAs (SR-STAs) and non-spatial reusable STAs (NSR-STAs). Because SR-STAs are more robust to interference than NSR-STAs, the DCA scheme prioritizes transmissions to SR-STAs over those to NSR-STAs by using differentiated carrier sensing thresholds. Moreover, the SPC scheme selectively increases the transmission power to NSR-STAs to compensate for transmission failure due to interference. By combining the SPC and DCA schemes, the proposed mechanism effectively differentiates the downlink transmissions to SR-STAs and NSR-STAs in terms of channel access and transmission power, and it can boost the possibility of successful SR. The proposed mechanism can be easily implemented in IEEE 802.11ax without any complex calculation or significant signaling overhead. Moreover, we provide a practical guideline to determine appropriate parameter values for use in the proposed mechanism. The extensive simulation results obtained in this study confirm that the proposed mechanism increases the downlink throughput by more than several times without decreasing the overall throughput, compared to the existing mechanisms, and it maintains fairness between SR-STAs and NSR-STAs in terms of the ratio of successful transmission.

Doc number: 490 Abstract Background: The four-herb Chinese medicine PHY906(KD018) has been shown to both enhance the in vivo antitumor activity of irinotecan (CPT-11) against colon cancer tumor allografts and alleviate intestinal toxicity caused by CPT-11. Methods: Since intestinal bacteria can metabolize CPT-11 and PHY906, we investigated whether intestinal bacteria play a critical role in the in vivo activity of PHY906 in murine Colon-38 tumor-bearing mice. Intestinal bacteria were depleted using streptomycin/neomycin for 10 days before and during treatment with PHY906 and/or CPT-11. qPCR using 16S DNA group-specific primers was used to quantify the levels of the major intestinal bacteria. Results: Both PHY906 and antibiotic treatment changed the profile of intestinal bacteria species: Lactobacillus/Enterococcus, Bacteroides, Clostridium leptum, and E. rectale/C. coccoides. Antibiotic treatment did not alter the ability of PHY906 to enhance the antitumor activity of CPT-11. Antibiotic treatment alone partially reduced animal body weight loss in CPT-11-treated mice. However, PHY906 treatment was able to protect against the body weight loss in the CPT-11/antibiotic treatment group. H&E and PCNA staining of intestine showed that antibiotic treatment partially reduced the intestinal damage caused by CPT-11 but not as effectively as PHY906 treatment. Antibiotic treatment plus PHY906 conferred the most effective protection of intestine histological structure against damage by CPT-11. Both PHY906 and antibiotic treatment inhibited CPT-11-associated inflammatory processes, including infiltration of the intestine by neutrophils, MCP1 and TNF-alpha mRNA expression in the intestine, and expression of pro-inflammatory cytokines G-CSF and MCP1 proteins in the plasma. However, whereas antibiotic treatment suppressed the mRNA expression of two important intestinal progenitor/stem cell markers, Olfm4 and Lgr5, PHY906 treatment resulted in enhanced expression of these two stem cell markers. Conclusions: Alterations in the population of intestinal bacteria did not affect the abilities of PHY906 to enhance CPT-11 antitumor activity or reduce the intestinal toxicity associated with CPT-11 treatment. The major species of intestinal bacteria do not appear to play a role in PHY906's enhancement of the therapeutic index of CPT-11 in tumor-bearing mice. Thus, patients with different intestinal bacterial profiles may still benefit from PHY906 treatment alongside CPT-11.

High fat, low carbohydrate ketogenic diets (KD) are validated non-pharmacological treatments for some forms of drug-resistant epilepsy. Ketones reduce neuronal excitation and promote neuroprotection. Here, we investigated the efficacy of KD as a treatment for acute cervical spinal cord injury (SCI) in rats. Starting 4 hours following C5 hemi-contusion injury animals were fed either a standard carbohydrate based diet or a KD formulation with lipid to carbohydrate plus protein ratio of 3:1. The forelimb functional recovery was evaluated for 14 weeks, followed by quantitative histopathology. Post-injury 3:1 KD treatment resulted in increased usage and range of motion of the affected forepaw. Furthermore, KD improved pellet retrieval with recovery of wrist and digit movements. Importantly, after returning to a standard diet after 12 weeks of KD treatment, the improved forelimb function remained stable. Histologically, the spinal cords of KD treated animals displayed smaller lesion areas and more grey matter sparing. In addition, KD treatment increased the number of glucose transporter-1 positive blood vessels in the lesion penumbra and monocarboxylate transporter-1 (MCT1) expression. Pharmacological inhibition of MCTs with 4-CIN (α-cyano-4-hydroxycinnamate) prevented the KD-induced neuroprotection after SCI, In conclusion, post-injury KD effectively promotes functional recovery and is neuroprotective after cervical SCI. These beneficial effects require the function of monocarboxylate transporters responsible for ketone uptake and link the observed neuroprotection directly to the function of ketones, which are known to exert neuroprotection by multiple mechanisms. Our data suggest that current clinical nutritional guidelines, which include relatively high carbohydrate contents, should be revisited.

Most medical implants are made of titanium. When titanium is exposed to air for a long time, hydrocarbons are deposited and the surface becomes hydrophobic. Cell attachment is important for bone ingrowth to occur on the implant surface, and hydrophilicity can enhance this. We examined whether non-thermal atmospheric pressure plasma treatment could increase the hydrophilicity of the titanium surface. Samples coated with four widely used coating types [grit blasting, micro arc oxidation (MAO), titanium plasma spray (TPS), and direct metal fabrication (DMF)] were treated with plasma. Each of the four surface-treated samples was divided into groups with and without plasma treatment. We analysed wettability by surface analysis and evaluation of contact angles, cell proliferation, and adhesion using scanning electron microscopy (SEM), confocal laser scanning microscopy, absorbance tests, and alkaline phosphatase (ALP) activity assay; four different Ti 6 Al 4 V surface types were compared. After plasma treatment, the contact angle was reduced on all surfaces, and the carbon content was reduced on all surfaces based on X-ray photoelectron spectroscopy (XPS) surface analysis. Under confocal laser scanning, the cell layer was thicker on the plasma-treated samples, especially in groups TPS and DMF. Cell proliferation was 41.8%, 17.7%, 54.9%, and 83.8% greater for the plasma- than non-plasma-treated grit blasting, MAO, TPS, and DMF samples, respectively. Hydrophilicity increased significantly under plasma treatment, and biological responsivity was also improved.

The secretary of the US Department of Health and Human Services in February 2016 recommended that X-linked adrenoleukodystrophy (X-ALD) be added to the recommended uniform screening panel for state newborn screening programs. This decision was informed by data presented on the accuracy of screening from New York, the only state that currently offers X-ALD newborn screening, and published and unpublished data showing health benefits of earlier treatment (hematopoietic stem cell transplantation and adrenal hormone replacement therapy) for the childhood cerebral form of X-ALD. X-ALD newborn screening also identifies individuals with later-onset disease, but poor genotype–phenotype correlation makes predicting health outcomes difficult and might increase the risk of unnecessary treatment. Few data are available regarding the harms of screening and presymptomatic identification. Significant challenges exist for implementing comprehensive X-ALD newborn screening, including incorporation of the test, coordinating follow-up diagnostic and treatment care, and coordination of extended family testing after case identification.

Continental shelves and shelf seas play a central role in the global carbon cycle. However, their importance with respect to trace element and isotope (TEI) inputs to ocean basins is less well understood. Here, we present major findings on shelf TEI biogeochemistry from the GEOTRACES programme as well as a proof of concept for a new method to estimate shelf TEI fluxes. The case studies focus on advances in our understanding of TEI cycling in the Arctic, transformations within a major river estuary (Amazon), shelf sediment micronutrient fluxes and basin-scale estimates of submarine groundwater discharge. The proposed shelf flux tracer is 228-radium (T1/2 = 5.75 yr), which is continuously supplied to the shelf from coastal aquifers, sediment porewater exchange and rivers. Model-derived shelf 228Ra fluxes are combined with TEI/ 228Ra ratios to quantify ocean TEI fluxes from the western North Atlantic margin. The results from this new approach agree well with previous estimates for shelf Co, Fe, Mn and Zn inputs and exceed published estimates of atmospheric deposition by factors of approximately 3–23. Lastly, recommendations are made for additional GEOTRACES process studies and coastal margin-focused section cruises that will help refine the model and provide better insight on the mechanisms driving shelf-derived TEI fluxes to the ocean. This article is part of the themed issue ‘Biological and climatic impacts of ocean trace element chemistry’.

DEAD box helicase 41 (DDX41) mutations are the most prevalent predisposition to familial myelodysplastic syndrome (MDS). However, the precise roles of these variants in the pathogenesis of MDS have yet to be elucidated. Here, we discovered a novel mechanism by which DDX41 contributes to R-loop-induced DNA damage responses (DDR) in cooperation with the m6A-METTL complex (MAC) and YTHDC1 using DDX41 knockout (KO) and DDX41 knock-in (KI, R525H, Y259C) cell lines as well as primary samples from MDS patients. Compared to wild type (WT), DDX41 KO and KI led to increased levels of m6A RNA methylated R-loop. Interestingly, we found that DDX41 regulates m6A/R-loop levels by interacting with MAC components. Further, DDX41 promoted the recruitment of YTHDC1 to R-loops by promoting the binding between METTL3 and YTHDC1, which was dysregulated in DDX41 -deficient cells, contributing to genomic instability. Collectively, we demonstrated that DDX41 plays a key role in the physiological control of R-loops in cooperation with MAC and YTHDC1. These findings provide novel insights into how defects in DDX41 influence MDS pathogenesis and suggest potential therapeutic targets for the treatment of MDS.

Background Using data from the Korean Hip Registry, we aimed to investigate mid-term clinical and radiographic outcomes, including the prevalence of periprosthetic joint infection (PJI), osteolysis, and component loosening or dislocation, and to analyze the incidence of bearing-related complications following modern ceramic-on-ceramic (COC) total hip arthroplasty (THA) using a single cementless hip system. Methods Four hundred eighty-two patients (602 hips) who underwent Forte or Delta COC THAs with a single hip system and had a minimum 5-year follow-up were identified. The sample included 243 (50.4%) women and 239 (49.6%) men with a mean age of 50.6 years (range: 18–83 years). The Forte group comprised 310 hips, and the Delta group comprised 292 hips. The mean follow-up was 6.1 years (range: 5–10.2 years). Results Cup orientation did not differ between groups. No hip had a PJI or osteolysis in either group. All acetabular components and all but two femoral components (in the Delta group) were well fixed. Dislocations occurred in six (1.9%) hips in the Forte group and one (0.3%) hip in the Delta group ( p  = 0.124). A total of nine (1.5%) revisions were performed. The 5-year survival rates for all-cause revisions were 98.4 and 98.6%, respectively. One (0.3%) ceramic head fracture occurred in the Forte group. Sixteen (5%) hips exhibited clicking and 6 (2%) hips had squeaking in the Forte group; 16 (6%) hips exhibited clicking and 5 (2%) hips had squeaking in the Delta group. Multiple regression analysis revealed that noise generation was unassociated with any factor. Conclusions From the Korean Hip Registry data, THA with modern ceramic bearings showed encouraging results, with lower risks of PJI, osteolysis, and component loosening. In particular, Delta COC THA resulted in no PJI or ceramic fracture and had a reduced dislocation risk. However, associated noise remains a concern.