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Background: To clarify the changes in the echo intensity (EI) in the prefemoral fat pad (PFP) and identify the relationship between the PFP and clinical features of knee osteoarthritis (OA). Methods: Twenty-six women with knee OA (mean age: 76 years) and 17 healthy women (mean age: 73 years) were enrolled. The Kellgren and Lawrence grading scale was used for the radiographic evaluation of knee OA. The EI of the PFP was measured as grayscale values. The change ratio of the anteroposterior PFP length during quadriceps contraction was measured. Knee range of motion and pain (100-mm visual analog scale) were evaluated. Results: The EI was significantly higher in the OA group than in the healthy group (P < 0.001). The change ratio of the PFP in the OA group was significantly lower than that in the healthy group (P < 0.001). The ranges of knee flexion and extension were correlated with the EI of the PFP (both P < 0.01) and the change ratio of the PFP (both P < 0.01). There was no significant correlation observed with knee pain. Conclusion: Hyperechoic changes and a decreased change ratio of the PFP were observed in the patients with knee OA. High EI and decreased morphological PFP changes were associated with decreased ranges of motion.

The availability of freshwater sources is declining as a result of increasing populations, economic activities, and climate change. These increasing trends will also drive up the demand for potable water that will require the use of alternative sources including wastewater-impacted and saline waters. Therefore, it is crucial to understand the formation of emerging toxic DBPs from advanced treatment of treated secondary wastewater effluents for potable reuse. In this study, a highly sensitive analytical method was developed to characterize 25 DBPs from 5 chemical classes (haloacetonitriles, halonitromethanes, haloacetaldehydes, haloketones, and iodinated trihalomethanes) in recycled wastewaters using a gas chromatography tandem mass spectrometer (MS/MS). The high sensitivity of MS/MS technology permitted a reduced sample concentration factor (50×) that required only 30 min of extraction time and 10 mL of sample volume. Method detection limits are the lowest reported between 2.0–68.9 ng L−1. Matrix effects in secondary wastewater effluents were low (0–30%) compared to ultra pure water. A full-scale facility for wastewater reuse that treated secondary wastewater effluents through microfiltration (UF), followed by ozone (UF/O3) or reverse osmosis (UF/RO) was evaluated. Water samples from each process were chlorinated (HOCl) and chloraminated (NH2Cl) to evaluate DBP precursor removal and DBP formation potential, the first study of its kind. Overall, HOCl formed higher summed DBP levels (0.5–18.5 μg L−1) compared to NH2Cl (0.2–8.5 μg L−1). HAN was significantly lower in UF/O3/HOCl (59%) and UF/RO/HOCl (99%) compared to UF/HOCl. However, HNM was enhanced after UF/O3/HOCl. In chloraminated samples, UF/O3/NH2Cl produced a higher amount of DBPs compared to UF/NH2Cl including haloacetonitriles, halonitromethanes, haloketones, and iodinated trihalomethanes.

Haloacetonitriles (HANs) are an emerging class of nitrogenous disinfection by-products (DBPs) formed in disinfected drinking water and have been reported to be more cyto- and genotoxic than the regulated DBPs. HANs are also known to hydrolyze under neutral pH and normal room temperature. However, the stability of HANs has not been well characterized in DBP toxicological assessments. Most toxicological assessments expose DBPs up to several days which may result in a mixture of HANs and degradation products that might have underestimated HAN toxicity. In this study, HANs stability was characterized in 1) a buffer solution in sealed vials, 2) cell culture media (CCM) in sealed vials, and 3) CCM in 96 sealed well plates with 5% CO

application/pdf, Journal of Nutrition, Health and Aging. 2022, 26 (2), P.157-160

Polycrystalline $${\hbox {La}}_{1-x}{\hbox {Sr}}_x{\hbox {ZnAsO}}$$ (0.00 $$\le $$ x $$\le $$ 0.075 ) was synthesized by solid-state reactions followed by hot pressing. The sign of the Seebeck coefficient changed from negative to positive by Sr doping, indicating that holes were successfully doped as a result of Sr substitutions. The maximum power factor of 0.118 mW/m K $$^2$$ was attained at $$T = 747$$ K in $$x = 0.05$$ . The thermal conductivity was relatively low at $$T = 773$$ K, with a value of approximately 1.9 W/m K independent of Sr doping. These results led to a dimensionless figure-of-merit ZT of 0.044 at $$T = 747$$ K in $$x = 0.05$$ .

Invariant natural killer T (iNKT) cells are innate‐like CD1d‐restricted T cells that express the invariant T cell receptor (TCR) composed of Vα24 and Vβ11 in humans. iNKT cells specifically recognize glycolipid antigens such as α‐galactosylceramide (αGalCer) presented by CD1d. iNKT cells show direct cytotoxicity toward CD1d‐positive tumor cells, especially when CD1d presents glycolipid antigens. However, iNKT cell recognition of CD1d‐negative tumor cells is unknown, and direct cytotoxicity of iNKT cells toward CD1d‐negative tumor cells remains controversial. Here, we demonstrate that activated iNKT cells recognize leukemia cells in a CD1d‐independent manner, however still in a TCR‐mediated way. iNKT cells degranulated and released Th1 cytokines toward CD1d‐negative leukemia cells (K562, HL‐60, REH) as well as αGalCer‐loaded CD1d‐positive Jurkat cells. The CD1d‐independent cytotoxicity was enhanced by natural killer cell‐activating receptors such as NKG2D, 2B4, DNAM‐1, LFA‐1 and CD2, but iNKT cells did not depend on these receptors for the recognition of CD1d‐negative leukemia cells. In contrast, TCR was essential for CD1d‐independent recognition and cytotoxicity. iNKT cells degranulated toward patient‐derived leukemia cells independently of CD1d expression. iNKT cells targeted myeloid malignancies more than acute lymphoblastic leukemia. These findings reveal a novel anti–tumor mechanism of iNKT cells in targeting CD1d‐negative tumor cells and indicate the potential of iNKT cells for clinical application to treat leukemia independently of CD1d., Activated human iNKT cells directly recognize leukemia cells, especially myeloid malignancies, in a CD1d‐independent manner. The CD1d‐independent cytotoxicity of iNKT cells depends on Vα24Vβ11‐T cell receptor and is enhanced by NK cell‐activating receptors.

Disinfection byproducts (DBPs) are a ubiquitous source of chemical exposure in drinking water and have been associated with serious health impacts in human epidemiologic studies. While toxicology studies have pinpointed DBPs with the greatest toxic potency, analytical methods have been lacking for quantifying complete classes of most toxic DBPs at sufficiently low quantification limits (ng/L). This new method reports the parts-per-trillion quantification for 61 toxicologically significant DBPs from 7 different chemical classes, including unregulated iodinated haloacetic acids (HAAs) and trihalomethanes (THMs), haloacetaldehydes, haloketones, haloacetonitriles, halonitromethanes, and haloacetamides, in addition to regulated HAAs and THMs. The final optimized method uses salt-assisted liquid-liquid extraction in a single extraction method for a wide range of DBPs, producing the lowest method detection limits to-date for many compounds, including highly toxic iodinated, brominated, and nitrogen-containing DBPs. Extracts were divided for the analysis of the HAAs (including iodinated HAAs) by diazomethane derivatization and analysis using a GC-triple quadrupole mass spectrometer with multiple reaction monitoring, resulting in higher signal-to-noise ratios, greater selectivity, and improved detection of these compounds. The remaining DBPs were analyzed using a GC-single quadrupole mass spectrometer with selected ion monitoring, utilizing a multimode inlet allowed for lower injection temperatures to allow the analysis of thermally labile DBPs. Finally, the use of a specialty-phase GC column (Restek Rtx-200) significantly improved peak shapes, which improved separations and lowered detection limits. Method detection limits for most DBPs were between 15 and 100 ng/L, and relative standard deviations in tap water samples were mostly between 0.2 and 30%. DBP concentrations in real samples ranged from 40 to 17 760 ng/L for this study.

We evaluated the efficacy of granular activated carbon (GAC) adsorption for mitigating formation of chlorine disinfection byproducts (DBPs) in water with a wide range of bromide (20–1000 μg L−1) and iodide ( 30 000 bed volumes). In the GAC influent, total organic bromine increased from 10 to 84% of TOX as bromide levels increased from 20 to 1000 μg L−1. Dissolved organic carbon (DOC) removal by GAC increased the bromide-to-DOC (Br/DOC) concentration ratio in GAC effluent relative to influent. As a result, bromine incorporation into DBPs increased after GAC treatment, especially at early GAC service times and low bromide levels. Total organic iodine was 50%) in all samples despite the quantification of 70 DBPs targeted in this study, highlighting the need to assess toxicity associated with unknown DBPs.

Accumulating evidence reveals that exposure to alternative flame retardants (AFRs) results in defective thyroid functions. AFRs are detectable in various environmental media in developed cities in China. However, few studies have reported the contamination levels of AFR in groundwater in rural areas, indicating an urgent need to investigate exposure of AFRs and perform health risk assessment for populations that use groundwater as the main source of drinking water. This study investigated the concentrations of AFRs in groundwater in rural areas of central China. Moreover, Nthy-ori-3-1 cells were used to determine the thyroid cytotoxicities and thyroid-interfering effects of a single AFR as well as the mixtures of AFRs based on the AFR contamination levels in real-world. The results revealed that all classes of AFRs were detectable in rural areas in central China. Dechlorane plus, hexabromocyclododecane, bromophenols (BPs), novel brominated flame retardants (NBFRs) and organophosphate flame retardants (OPFRs) exhibited spatial contamination patterns, with an average concentrations (median) of 157.89 ± 88.61 (185.47) pg/L, 0.09 ± 0.29 (not detectable) ng/L, 5.20 ± 5.92 (3.43) ng/L, 3338.11 ± 3758.78 (2836.72) pg/L, and 79.35 ± 97.19 (53.62) ng/L, respectively. The half maximal effective concentrations (EC

Plastics and biofilms have a complicated relationship that has great interest. Bacterial cell attachment and biofilm formation is considered to cause health and environmental risks from plastic waste accumulation. In water, plastic waste could serve as a new substrate for bacteria. In our study, the attachment of Escherichia coli K12, to four types of plastic shopping bags (biodegradable polylactic acid and the non-biodegradable polypropylene, polyethylene and polyvinyl chloride) was investigated. The change in physicochemical phenomena of each plastic, such as reduced hydrophobicity and higher exopolysaccharide concentrations (total extractable protein and carbohydrate) resulted in increased biofilm content on the plastic surfaces. The bacterial colonization of different plastic surfaces controls the ionic strength of the nutrition sources. The adhesion of Escherichia coli K12 cells on the surfaces were revealed by SEM images. The finding shows that increases surface roughness, besides favor for adhesion of bacterial cells due to hydrophobicity leading to a rapid attachment of Escherichia coli K12 on the surfaces. In addition, we used Derjaguin-Landau-Verwey-Overbeek theory to predict the attachment of Escherichia coli K12, which gave result of adhesion due to the high energy barrier. This present study added to our knowledge of the possible consequences of plastics acting as a new habitat for microbes in different aquatic condition.

The integration of high aspect-ratio (AR) vias or supervias (SV) with a min CD bottom = 10.5 nm and a max AR = 5.8 is demonstrated, allowing a comparison between ruthenium (Ru) and cobalt (Co) chemical vapor deposition (CVD) metallizations. Ru gave a resistance ~2x higher than Co when a 1.1 nm titanium nitride (TiN) film, realized by atomic layer deposition (ALD), was used as an adhesion/nucleation layer. The lowest SV resistance of 56 Ω at the median was obtained with 0.3 nm of titanium oxide (TiOx) ALD and Ru CVD. This configuration gave a 3.4x lower resistance than the equivalent scheme with 0.3 nm TiN ALD and 15% lower resistance than the stacked-via configuration (with 0.3 nm TiOx and Ru fill), meaning that an IR-drop penalty is avoided when compared to the stacked-via approach. A congestion reduction can also be expected from the CD reduction of the SVs as the exclusion area in the intermediate layer can be smaller. Thermal shock tests for both Ru and Co SVs produced no failure after 1000 cycles between −50 °C and 125 °C, and 250 hours.

Vertebrate vestibular circuits use sensory signals derived from the inner ear to guide both corrective and volitional movements. A major challenge in the neuroscience of balance is to link the synaptic and cellular substrates that encode body tilts to specific behaviors that stabilize posture and enable efficient locomotion. Here we address this problem by measuring the development, synaptic architecture, and behavioral contributions of vestibulospinal neurons in the larval zebrafish. First, we find that vestibulospinal neurons are born and are functionally mature before larvae swim freely, allowing them to act as a substrate for postural regulation. Next, we map the synaptic inputs to vestibulospinal neurons that allow them to encode posture. Further, we find that this synaptic architecture allows them to respond to linear acceleration in a directionally-tuned and utricle-dependent manner; they are thus poised to guide corrective movements. After loss of vestibulospinal neurons, larvae adopted eccentric postures with disrupted movement timing and weaker corrective kinematics. We used a generative model of swimming to demonstrate that together these disruptions can account for the increased postural variability. Finally, we observed that lesions disrupt vestibular-dependent coordination between the fins and trunk during vertical swimming, linking vestibulospinal neurons to navigation. We conclude that vestibulospinal neurons turn synaptic representations of body tilt into defined corrective behaviors and coordinated movements. As the need for stable locomotion is common and the vestibulospinal circuit is highly conserved our findings reveal general mechanisms for neuronal control of balance.

Regarding vascularized lymph node transfer (VLNT) for lymphedema, partial blood flow impairment in transferred lymph node (LN) flaps may adversely affect the therapeutic results. We investigated the clinical and histological effects of partial blood flow impairment in LN flaps. In upper extremity lymphedema cases, based on ultrasonographic examination at 2 weeks after VLNT, we compared the treatment results depending on whether the postoperative blood flow in transferred LNs was good (Group G) or poor (Group P). Novel partial ischemia and congestion of LN flap mouse models were developed to determine their histological features. In 42 cases, significant differences were observed between Group G (n = 37) and Group P (n = 5) based on the amount of volume reduction (136.7 ± 91.7 mL and 55.4 ± 60.4 mL, respectively; p = 0.04) and lymph flow recanalization rate in indocyanine green fluorescent lymphography (67.6% and 0%, respectively; p = 0.0007). In mouse models, thrombi formation in the marginal sinus and numerous Myl9/12-positive immunocompetent cells in follicles were observed in congested LNs. Blood flow maintenance in the transferred LNs is an essential factor influencing the therapeutic effect of VLNT. Postoperatively, surgeons should closely monitor blood flow in the transferred LNs, particularly in cases of congestion.

While many academic conferences are transitioning to online events, this article aims to share several strategies used by the organizers of a well-established online-only conference. The Teaching, Colleges, and Community (TCC) Worldwide Online Conference recently celebrated its 25th anniversary. After a brief review of TCC’s history, four strategies that organizers have identified as helping conference goers feel oriented, welcomed, connected and engaged are described. These strategies include offering a “pre-conference” orientation, including regional keynote speakers, creating opportunities for informal exchange, and encouraging participation with digital credentials.

Funding Acknowledgements Type of funding sources: None. Background Occurrence of ventricular tachycardias (VT) has been related to changes in sympathetic innervation and myocardial tissue in ischemic cardiomyopathy. In non-ischemic cardiomyopathy (NICM) patients with VT, the relation between global cardiac sympathetic innervation and non-ischemic fibrosis is less clear. The current gold standard in electrophysiology to identify non-ischemic fibrosis relies on unipolar endocardial voltage mapping. Objective To establish the relationship between global cardiac sympathetic innervation and global fibrosis. Methods 29 patients (93% male, 58 ± 14 years, mean LVEF 38%±13) from the ‘Leiden Nonischemic Cardiomyopathy Study’ undergoing VT ablation between 2011-2018 were included. Endocardial voltage mapping was performed and the mean endocardial unipolar voltage (UV) was taken as a surrogate for global fibrosis. Global cardiac sympathetic innervation was analyzed by 123-I-MIBG imaging using heart-to-mediastinum ratio (HMR). A cut-off of 1.8 was used to delineate between normal (>1.8) and denervated ( Results For patients with global cardiac sympathetic denervation a linear relationship was present between HMR and mean UV (R = 0.5278, P = 0.0431. There was no significant linear relationship for patients with normal cardiac sympathetic innervation between HMR and mean UV (R=-0.1696, P = 0.5795). Conclusion Global cardiac sympathetic denervation is related to myocardial fibrosis in patients with NICM and VT. The data support an interplay between denervation and fibrosis which may contribute to arrhythmogeneity, as observed in ICM. Abstract Figure.

Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation - Projektnummer 447558597) Background Among patients with non-ischemic cardiomyopathy (NICM) two dominant ventricular tachycardia (VT) substrate locations, namely anteroseptal (AS) and inferolateral (IL), have been identified. The poor outcome after catheter ablation of AS substrates (ASS) compared to IL substrates (ILS) has been attributed to its deep intramural location. However, region specific tissue charateristics, including sympathetic innervation, as important determinant of arrhythmogeneity, may also contribute to the outcome disparity. Aim To evaluate the association between regional sympathetic denervation, myocardial fibrosis and VT substrates according to two dominant VT substrate locations. Methods Twenty-nine patients from the ‘Leiden Nonischemic Cardiomyopathy Study’, who underwent electroanatomical substrate mapping and radiofrequency catheter ablation (RFCA), LGE-CMR and 123-I-MIBG imaging between 2011-2018 were included. The 16-segment model was used to describe the distribution of endocardial low unipolar voltage (UV Results Ten patients had a dominant ASS, 12 patients a dominant ILS and 1 patient had ASS and ILS; 6 patients had other VT substrate locations. All but one patient with ASS and one with ILS also showed corresponding low UV (=surrogate for fibrosis) in segments with VT substrates. Eight patients with IL VT substrates but only 4 with AS substrates showed corresponding LGE in the VT related segments. All patients with inferolateral VT substrates showed sympathetic denervation in IL segments (100% matching segments), but only 3/11 (27%) with anteroseptal substrates had sympathetic denervation in AS segments (P = 0.0002). UV was not significantly different between matching (VT substrate and denervation) and not matching ASS segments (5.74 ± 2.69 mV vs. 4.64 ± 1.85 mV, P = 0.78) and between matching ASS and ILS segments (5.74 ± 2.69 mV vs. 7.61 ± 2.91, P = 0.43). LGE location was matching with sympathetic denervation in all patients with ILS but only in 33% of patients with ASS. Conclusion Despite low endocardial UV (=surrogate for fibrosis) for AS and IL segments harboring VT substrates, regional sympathetic denervation coincided with fibrosis only for IL VT substrates. The mismatch between regional fibrosis and preserved innervation for AS VT substrates may contribute to a VT substrate difficult to control by RFCA.

Funding Acknowledgements Type of funding sources: None. Background Patients with dilated cardiomyopathy (DCM) and ventricular tachyarrhythmias (VT) are at risk for heart failure (HF) death. Global left ventricular endocardial voltage may reflect the amount of excitable viable myocardium and identify patients at risk for rapid progression to end-stage HF. Aim To determine if volume-weighted endocardial voltage, as a surrogate for the total excitable viable myocardium, predicts mortality in patients with DCM and VT. Methods Consecutive patients with DCM, who underwent high-density endocardial voltage mapping for VT or PVC ablation (2012-2018), were included. Mapping data were transferred from CARTO to ParaView after excluding valve areas. The volume-weighted UV and BV (vwUV, vwBW) were calculated by mathematically integrating the UV and BV over the whole LV (thereby correcting for mapping density heterogeneity) divided by the endocardial LV surface area and corrected for LV wall thickness determined by echocardiography. The prognostic values of vwUV and vwBV for cardiac function and cardiac death were evaluated. Results One hundred three patients (VT, n = 83 and PVC, n = 20; age, 57 ± 14yrs; LVEF, 39 ± 13%; [likely] pathogenic genetic variants 33 [32%]; amiodarone use 36 [35%]) were included. VwUV and vwBV were 9.94 ± 3.42 and 4.70 ± 1.46. During a median follow-up of 24 months, cardiac mortality was 18% (end-stage HF 16/19, the median time to death 5.7 months). Patients who died had a significantly lower vwUV and vwBV (vwUV 5.62 ± 0.93 vs. 10.91 ± 3.10, P 5% and transition to HFrEF) occurred in 22% and was strongly related with a low vwUV (6.65 ± 1.15 vs. 10.08 ± 2.92, P = 0.02, Figure B left). Furthermore, in patients with HFrEF, a significant LVEF improvement (defined as an EF increase >5% and transition to HFmrEF) was noted in 32% and was correlated with a high vwUV (11.68 ± 2.70 vs. 8.62 ± 2.69, P = 0.002, Figure B right). Conclusion VwUV is a newly proposed surrogate for the amount of LV viable myocardium, available from routine endocardial mapping and an excellent parameter to identify patients with DCM at high risk for rapid progression to HF-related death. Abstract Figure. vwUV and outcomes

IntroductionDirect-to-family clinical trials efficiently provide data while reducing the participation burden for children and their families. Although these trials can offer significant advantages over traditional clinical trials, the process of designing and implementing direct-to-family studies is poorly defined, especially in children with rheumatic disease. This paper provides lessons learnt from the design and implementation of a self-controlled, direct-to-family pilot trial aimed to evaluate the effects of a medication management device on adherence to hydroxychloroquine in paediatric SLE.MethodsSeveral design features accommodate a direct-to-family approach. Participants meeting eligibility criteria from across the USA were identified a priori through a disease registry, and all outcome data are collected remotely. The primary outcome (medication adherence) is evaluated using electronic medication event-monitoring, plasma drug levels, patient questionnaires and pill counts. Secondary and exploratory endpoints include (1) lupus disease activity measured by a remote SLE Disease Activity Index examination and the Systemic Lupus Activity Questionnaire; and (2) hydroxychloroquine pharmacokinetics and pharmacodynamics. Recruitment of the initial target of 20 participants was achieved within 10 days. Due to initial recruitment success, enrolment was increased to 26 participants. Additional participants who were interested were placed on a waiting list in case of dropouts during the study.Discussion and disseminationDirect-to-family trials offer several advantages but present unique challenges. Lessons learnt from the protocol development, design, and implementation of this trial will inform future direct-to-family trials for children and adults with rheumatic diseases. Additionally, the data collected remotely in this trial will provide critical information regarding the accuracy of teleresearch in lupus, the impact of adherence to hydroxychloroquine on disease activity and a pharmacokinetic analysis to inform paediatric-specific dosing of hydroxychloroquine.Trial registration numberClinicalTrials.gov Registry (NCT04358302).

O Grupo Cataratas de Eficiência Energética (GCEE) é constituído por docentes e discentes do CECE da Unioeste - Foz do Iguaçu, e tem por finalidade enriquecer a formação de seus integrantes por meio de atividades de projeto, construção e manejo de veículos para competições de eficiência energética para veículos movidos à energia elétrica e etanol. A equipe já participou de diversas competições sendo a detentora do recorde latino-americano na categoria etanol (736 Km com um litro de etanol).

Flame retardants have evoked public concerns owing to their extensive usage in consumer products and potential adverse effects on human health. In this study, a rapid and sensitive solid-phase extraction-ultra-high-performance liquid chromatography-tandem mass spectrometry (SPE-UPLC-MS/MS) method was developed to determine hexabromocyclododecane (HBCD), tetrabromobisphenol-A (TBBPA), six bromophenols (BPs), and nine organophosphate flame retardants (OPFRs) in water. Because of the differences in elution conditions and ionization modes for group 1 (HBCD, TBBPA, and the BPs) and group 2 (OPFRs), we had to run them twice under the different conditions to analyse group 1 and group 2 using UPLC-MS/MS. The method detection limits were 0.1–2.5 ng/L, linearity range was 0.1–100.0 ng/L for group 1 (HBCD, TBBPA, and the BPs). The method detection limit was 0.10 ng/L, and the linearity range was 0.25–250 ng/L for the OPFRs. First, the pH values of the water samples were adjusted to the range of 2–3. Then, the acidified water samples were extracted by hydrophilic-lipophilic-balance solid phase extraction (HLB-SPE) cartridges, which were eluted with 12 mL of acetonitrile. Finally, the recoveries of HBCD, TBBPA, and the BPs were 76.2–98.1%, and the relative standard deviations (RSDs, n = 5) were 2.0–28.5%. Regarding the OPFRs, the recoveries were 72.4–110.3%, and the RSDs were 0.6–6.9%. The stability experiment showed that the concentration differences were less than 15%, meeting the requirement for quality control samples. This proposed method was successfully applied to surface water, ground water, raw water, finished water, tap water, and bottled water samples.

Granular activated carbon (GAC) adsorption is well-established for controlling regulated disinfection byproducts (DBPs), but its effectiveness for unregulated DBPs and DBP-associated toxicity is unclear. In this study, GAC treatment was evaluated at three full-scale chlorination drinking water treatment plants over different GAC service lives for controlling 61 unregulated DBPs, 9 regulated DBPs, and speciated total organic halogen (total organic chlorine, bromine, and iodine). The plants represented a range of impacts, including algal, agricultural, and industrial wastewater. This study represents the most extensive full-scale study of its kind and seeks to address the question of whether GAC can make drinking water safer from a DBP perspective. Overall, GAC was effective for removing DBP precursors and reducing DBP formation and total organic halogen, even after22 000 bed volumes of treated water. GAC also effectively removed preformed DBPs at plants using prechlorination, including highly toxic iodoacetic acids and haloacetonitriles. However, 7 DBPs (mostly brominated and nitrogenous) increased in formation after GAC treatment. In one plant, an increase in tribromonitromethane had significant impacts on calculated cytotoxicity, which only had 7-17% reduction following GAC. While these DBPs are highly toxic, the total calculated cytotoxicity and genotoxicity for the GAC treated waters for the other two plants was reduced 32-83% (across young-middle-old GAC). Overall, calculated toxicity was reduced post-GAC, with preoxidation allowing further reductions.

CD69 is an activation marker on leukocytes. Early studies showed that the CD69+ cells were detected in the lung of patients with asthmatic and eosinophilic pneumonia, suggesting that CD69 might play crucial roles in the pathogenesis of such inflammatory diseases, rather than simply being an activation marker. Intensive studies using mouse models have since clarified that CD69 is a functional molecule regulating the immune responses. We discovered that Myosin light chain 9, 12a, 12b (Myl9/12) are ligands for CD69 and that platelet-derived Myl9 forms a net-like structure (Myl9 nets) that is strongly detected inside blood vessels in inflamed lung. CD69-expressing activated T cells attached to the Myl9 nets can thereby migrate into the inflamed tissues through a system known as the CD69-Myl9 system. In this review, we summarize the discovery of the CD69-Myl9 system and discuss how this system is important in inflammatory immune responses. In addition, we discuss our recent finding that CD69 controls the exhaustion status of tumor-infiltrating T cells and that the blockade of the CD69 function enhances anti-tumor immunity. Finally, we discuss the possibility of CD69 as a new therapeutic target for patients with intractable inflammatory disorders and tumors.

Water disinfection is used in drinking water treatment to protect public health by controlling microbial pathogens that cause waterborne diseases. Water disinfectants also react with natural organic matter found in source waters to unintentionally produce disinfection byproducts (DBPs). However, with increasing populations and climate change, water sources are receiving anthropogenic inputs that differ from natural organic matter. These changes trigger the formation of a new suite of DBPs with unknown formation mechanisms. This review provides an overview of recent research on DBP formation mechanisms and analytical methods of priority DBPs including N-halamines, organic and inorganic amines, nitrosamines, total organic halogen, and DBPs derived from advanced oxidation processes including combined UV/chlorine processes. Key intermediates responsible for DBP formation which were previously unnoticed and new analytical method developments are also highlighted.

Introduction Although we previously demonstrated in rats that combination of a dopamine (DA) receptor agonist and 5-HT2 receptor agonist potently and selectively facilitates the ejaculatory response through the activation of D2-like and 5-HT2C receptors, these central mechanisms are not fully understood. We therefore investigated to clarify the target level of the pro-ejaculatory effects by combination of these agonists. Methods The ejaculatory response was evaluated 30 min after drug administration by the presence of seminal materials on the paper towel as well as that adhering to the shaft of the penis. In addition, we examined isolated rat seminal vesicle contraction. Results Intrathecal administration of 5-HT2 receptor agonist m-CPP (10 μg) but not in intracerebroventricular evoked the synergistic action for ejaculation in the combination with systemic administrated DA receptor agonist apomorphine (0.1 mg/kg, s.c.). Synergy effects of combination were completely inhibited by intrathecal 5-HT2C receptor antagonist SB242084 (10 μg). Intrathecal or intracerebroventricular apomorphine (1-10 μg) evoked the pro-ejaculatory effects in the combination with systemic administrated m-CPP (0.3 mg/kg, i.p.) The selective peripherally acting D2-like receptor agonist carmoxirole did not evoked in the combination with m-CPP. Furthermore, the combination of apomorphine and m-CPP did not produce contraction of rat seminal vesicle. Conclusion These results suggest that this synergistic action for ejaculation induces in the spinal or supraspinal level but not the peripheral sites. Furthermore, the present study suggests that the activation of the spinal ejaculatory pattern generator through 5-HT2C receptors is synergistically potentiated by both spinal and supraspinal DA receptors. Disclosure Work supported by industry: no.

In drinking water disinfection, switching from free chlorine to alternative chemical disinfectants such as monochloramine may result in the formation of different classes of toxic disinfection byproducts (DBPs). Haloacetonitriles (HANs) and haloacetamides (HAMs) are two currently unregulated nitrogen-containing DBP (N-DBP) groups commonly found in water disinfected with monochloramine that have been shown to be more cyto- and genotoxic than regulated DBPs. For the first time, this study confirms the formation of HAN and HAM dominant species found in disinfected water, dichloroacetonitrile and dichloroacetamide, from the reaction between monochloramine and dichloroacetaldehyde via the aldehyde reaction pathway. Results from experiments with natural water treated with labeled

The numbers of patients with inflammatory bowel disease (IBD), such as ulcerative colitis (UC) and Crohn’s disease (CD), have been increasing over time, worldwide; however, the pathogenesis of IBD is multifactorial and has not been fully understood. Myosin light chain 9 and 12a and 12b (Myl9/12) are known as ligands of the CD69 molecule. They create “Myl9 nets” that are often detected in inflamed site, which play a crucial role in regulating the recruitment and retention of CD69-expressing effector cells in inflamed tissues. We demonstrated the strong expression of Myl9/12 in the inflamed gut of IBD patients and mice with DSS-induced colitis. The administration of anti-Myl9/12 Ab to mice with DSS-induced colitis ameliorated the inflammation and prolonged their survival. The plasma Myl9 levels in the patients with active UC and CD were significantly higher than those in patients with disease remission, and may depict the disease severity of IBD patients, especially those with UC. Thus, our results indicate that Myl9/12 are involved in the pathogenesis of IBD, and are likely to be a new therapeutic target for patients suffering from IBD.

While IFNγ is a well-known cytokine that actively promotes the type I immune response, it is also known to suppress the type II response by inhibiting the differentiation and proliferation of Th2 cells. However, the mechanism by which IFNγ suppresses Th2 cell proliferation is still not fully understood. We found that IFNγ decreases the expression of growth factor independent-1 transcriptional repressor (GFI1) in Th2 cells, resulting in the inhibition of Th2 cell proliferation. The deletion of theGfi1gene in Th2 cells results in the failure of their proliferation, accompanied by an impaired cell cycle progression. In contrast, the enforced expression of GFI1 restores the defective Th2 cell proliferation, even in the presence of IFNγ. These results demonstrate that GFI1 is a key molecule in the IFNγ-mediated inhibition of Th2 cell proliferation.

We present the first observation by the Telescope Array Surface Detector (TASD) of the effect of thunderstorms on the development of cosmic ray single count rate intensity over a 700 km$^{2}$ area. Observations of variations in the secondary low-energy cosmic ray counting rate, using the TASD, allow us to study the electric field inside thunderstorms, on a large scale, as it progresses on top of the 700 km$^{2}$ detector, without dealing with the limitation of narrow exposure in time and space using balloons and aircraft detectors. In this work, variations in the cosmic ray intensity (single count rate) using the TASD, were studied and found to be on average at the $\sim(0.5-1)\%$ and up to 2\% level. These observations were found to be both in excess and in deficit. They were also found to be correlated with lightning in addition to thunderstorms. These variations lasted for tens of minutes; their footprint on the ground ranged from 6 to 24 km in diameter and moved in the same direction as the thunderstorm. With the use of simple electric field models inside the cloud and between cloud to ground, the observed variations in the cosmic ray single count rate were recreated using CORSIKA simulations. Depending on the electric field model used and the direction of the electric field in that model, the electric field magnitude that reproduces the observed low-energy cosmic ray single count rate variations was found to be approximately between 0.2-0.4 GV. This in turn allows us to get a reasonable insight on the electric field and its effect on cosmic ray air showers inside thunderstorms.

integration requires development of low thermal budget process modules. High-quality SiO 2 interfacial layer (IL), obtained up to now only by high-temperature (≥850°C) oxidation or exposure, is crucial for pMOS NBTI reliability. In unannealed IL’s grown at reduced temperatures, we show that unrelaxed interface strain induces high defect densities, with physics-based NBTI modeling suggesting excessive hydroxyl-E’ defect formation due to Si-O bond stretch. Based on ab-initio theoretical insights, we demonstrate an atomic hydrogen treatment to passivate SiO 2 defects at low temperatures (100-300°C), which is shown to be vastly more effective than high pressure molecular hydrogen exposure, and to yield an SiO 2 quality and reliability surpassing a 900°C oxide.

The integration of high-aspect-ratio (AR) supervias (SV) into a 3 nm node test vehicle, bypassing an intermediate 21 nm pitch layer, is demonstrated. Place-and-route (PnR) simulations of the Power Delivery Network (PDN) proved IR-drop reduction with respect to the stacked-via configuration. SV first and SV last integration approaches were electrically tested using full barrierless ruthenium (Ru) on a dielectric low-k 3.0. A maximum AR = 3.8 was achieved with ~2.4 times lower resistance than the alternative stacked-via configuration. Thermal shock tests produced no SV failure after 1000 cycles between -50 °C and 125 °C, and 250 hours. Time-dependent-dielectric-breakdown (TDDB) tests between SV and M2 lines gave a TTF 63.2% (at 1 MV/cm) > 10 years, when 3 M2 tracks are blocked.