166 research outputs found
Increasing the Safety in Recycling of Construction and Demolition Waste by Using Supervised Machine Learning
This paper discusses the possibility of the optical identification of recycled aggregates of construction and demolition waste (CDW) using methods of image processing, spectral analysis and machine learning. The classification performances in colour images shown, that we have to use other added spectral information to solve the recognition task in a satisfactory manner. In addition to investigations on a large colour image dataset first investigations in visible (VIS) and infrared (IR) spectrum were done for analysing significant characteristics in spectrum, which are useful for classification the C&D aggregates
TERT promoter mutations are highly recurrent in SHH subgroup medulloblastoma
Telomerase reverse transcriptase (TERT) promoter mutations were recently shown to drive telomerase activity in various cancer types, including medulloblastoma. However, the clinical and biological implications of TERT mutations in medulloblastoma have not been described. Hence, we sought to describe these mutations and their impact in a subgroup-specific manner. We analyzed the TERT promoter by direct sequencing and genotyping in 466 medulloblastomas. The mutational distributions were determined according to subgroup affiliation, demographics, and clinical, prognostic, and molecular features. Integrated genomics approaches were used to identify specific somatic copy number alterations in TERT promoter-mutated and wild-type tumors. Overall, TERT promoter mutations were identified in 21 % of medulloblastomas. Strikingly, the highest frequencies of TERT mutations were observed in SHH (83 %; 55/66) and WNT (31 %; 4/13) medulloblastomas derived from adult patients. Group 3 and Group 4 harbored this alteration in <5 % of cases and showed no association wit
Caspase involvement in autophagy
Caspases are a family of cysteine proteases widely known as the principal mediators of the apoptotic cell death response, but considerably less so as the contributors to the regulation of pathways outside cellular demise. In regards to autophagy, the modulatory roles of caspases have only recently begun to be adequately described. In contrast to apoptosis, autophagy promotes cell survival by providing energy and nutrients through the lysosomal degradation of cytoplasmic constituents. Under basal conditions autophagy and apoptosis cross-regulate each other through an elaborate network of interconnections which also includes the interplay between autophagyrelated proteins (ATGs) and caspases. In this review we focus on the effects of this crosstalk at the cellular level, as we aim to concentrate the main observations from research conducted so far on the fine-tuning of autophagy by caspases. Several members of this protease-family have been found to directly interact with key ATGs involved in different tiers across the autophagic cascade. Therefore, we firstly outline the core mechanism of macroautophagy in brief. In an effort to emphasize the importance of the intricate cross-regulation of ATGs and caspases, we also present examples drawn from Drosophila and plant models regarding the contribution of autophagy to apoptotic cell death during normal development
Risk Factors for Nonaccidental Burns in Children
BACKGROUND: The relative influences of baseline risk factors for pediatric nonaccidental burns have not been well described. We evaluated baseline characteristics of pediatric nonaccidental burn patients and their primary caretakers.
METHODS: A single-center retrospective cohort study was conducted of pediatric (age \u3c 17) burn patients from July 1, 2013, to June 30, 2018. The primary outcome was nonaccidental burn, defined as burn secondary to abuse or neglect as determined by the inpatient child protection team or Child Protective Services. Univariate and multivariate analyses were performed.
RESULTS: Of 489 burn patients, 47 (9.6%) suffered nonaccidental burns. Nonaccidental burn patients more frequently had a history of Child Protective Services involvement (48.9% vs 9.7%, P \u3c .001), as did their primary caretakers (59.6% vs 10.9%, P \u3c .001). Non-Hispanic black children had higher rates of Child Protective Services referral (50.7% vs 26.7%, P \u3c .001) and nonaccidental burn diagnosis (18.9% vs 5.6%, P \u3c .001) than children of other races/ethnicities. On multivariate analysis, caretaker involvement with CPS (odds ratio 7.53, 95% confidence interval 3.38-16.77) and non-Hispanic black race/ethnicity (odds ratio 3.28, 95% confidence interval 1.29-8.36) were associated with nonaccidental burn.
CONCLUSION: Caretaker history of Child Protective Services involvement and non-Hispanic black race/ethnicity were associated with increased odds of pediatric nonaccidental burn. Prospective research is necessary to determine whether these represent true risk factors for nonaccidental burn or are the result of other confounders, such as socioeconomic status
Oxidation of HMGB1 Causes Attenuation of Its Pro-Inflammatory Activity and Occurs during Liver Ischemia and Reperfusion
High mobility group box 1 (HMGB1) is a nuclear transcription factor. Once HMGB1 is released by damaged cells or activated immune cells, it acts as danger molecule and triggers the inflammatory signaling cascade. Currently, evidence is accumulating that posttranslational modifications such as oxidation may modulate the pro-inflammatory potential of danger signals. We hypothesized that oxidation of HMGB1 may reduce its pro-inflammatory potential and could take place during prolonged ischemia and upon reperfusion
Addition of Amines to a Carbonyl Ligand: Syntheses, Characterization, and Reactivities of Iridium(III) Porphyrin Carbamoyl Complexes
Treatment of (carbonyl)chloro(meso-tetra-p-tolylporphyrinato)iridium(III), (TTP)Ir(CO)Cl (1), with excess primary amines at 23 °C in the presence of Na2CO3 produces the trans-amine-coordinated iridium carbamoyl complexes (TTP)Ir(NH2R)[C(O)NHR] (R = Bn (2a), n-Bu (2b), i-Pr (2c), t-Bu (2d)) with isolated yields up to 94%. The trans-amine ligand is labile and can be replaced with quinuclidine (1-azabicyclo[2.2.2]octane, ABCO), 1-methylimidazole (1-MeIm), triethyl phosphite (P(OEt)3), and dimethylphenylphosphine (PMe2Ph) at 23 °C to afford the hexacoordinated carbamoyl complexes (TTP)Ir(L)[C(O)NHR] (for R = Bn: L = ABCO (3a), 1-MeIm (4a), P(OEt)3 (5a), PMe2Ph (6a)). On the basis of ligand displacement reactions and equilibrium studies, ligand binding strengths to the iridium metal center were found to decrease in the order PMe2Ph \u3e P(OEt)3 \u3e 1-MeIm \u3e ABCO \u3e BnNH2 ≫ Et3N, PCy3. The carbamoyl complexes (TTP)Ir(L)[C(O)NHR] (L = RNH2 (2a,b), 1-MeIm (4a)) undergo protonolysis with HBF4 to give the cationic carbonyl complexes [(TTP)Ir(NH2R)(CO)]BF4 (7a,b) and [(TTP)Ir(1-MeIm)(CO)]BF4 (8), respectively. In contrast, the carbamoyl complexes (TTP)Ir(L)[C(O)NHR] (L = P(OEt)3 (5a), PMe2Ph (6a,c)) reacted with HBF4 to afford the complexes [(TTP)Ir(PMe2Ph)]BF4 (9) and [(TTP)IrP(OEt)3]BF4 (10), respectively. The carbamoyl complexes (TTP)Ir(L)[C(O)NHR] (L = RNH2 (2a–d), 1-MeIm (4a), P(OEt)3 (5b), PMe2Ph (6c)) reacted with methyl iodide to give the iodo complexes (TTP)Ir(L)I (L = RNH2 (11a–d), 1-MeIm (12), P(OEt)3(13), PMe2Ph (14)). Reactions of the complexes [(TTP)Ir(PMe2Ph)]BF4 (9) and [(TTP)IrP(OEt)3]BF4 (10) with [Bu4N]I, benzylamine (BnNH2), and PMe2Ph afforded (TTP)Ir(PMe2Ph)I (14), (TTP)Ir[P(OEt)3]I (13), [(TTP)Ir(PMe2Ph)(NH2Bn)]BF4 (16), and trans-[(TTP)Ir(PMe2Ph)2]BF4 (17), respectively. Metrical details for the molecular structures of 4a and17 are reported
Serum Potassium and Risk of Death or Kidney Replacement Therapy in Older People With CKD Stages 4-5: Eight-Year Follow-up
Rationale & Objective: Hypokalemia may accelerate kidney function decline. Both hypo- and hyperkalemia can cause sudden cardiac death. However, little is known about the relationship between serum potassium and death or the occurrence of kidney failure requiring replacement therapy (KRT). We investigated this relationship in older people with chronic kidney disease (CKD) stage 4-5. Study Design: Prospective observational cohort study. Setting & Participants: We followed 1,714 patients (≥65 years old) from the European Quality (EQUAL) study for 8 years from their first estimated glomerular filtration rate (eGFR) < 20 mL/min/1.73 m2 measurement. Exposure: Serum potassium was measured every 3 to 6 months and categorized as ≤3.5, >3.5-≤4.0, >4.0-≤4.5, >4.5-≤5.0 (reference), >5.0-≤5.5, >5.5-≤6.0, and >6.0 mmol/L. Outcome: The combined outcome death before KRT or start of KRT. Analytical Approach: The association between categorical and continuous time-varying potassium and death or KRT start was examined using Cox proportional hazards and restricted cubic spline analyses, adjusted for age, sex, diabetes, cardiovascular disease, renin-angiotensin-aldosterone system (RAAS) inhibition, eGFR, and subjective global assessment (SGA). Results: At baseline, 66% of participants were men, 42% had diabetes, 47% cardiovascular disease, and 54% used RAAS inhibitors. Their mean age was 76 ± 7 (SD) years, mean eGFR was 17 ± 5 (SD) mL/min/1.73 m2, and mean SGA was 6.0 ± 1.0 (SD). Over 8 years, 414 (24%) died before starting KRT, and 595 (35%) started KRT. Adjusted hazard ratios for death or KRT according to the potassium categories were 1.6 (95% CI, 1.1-2.3), 1.4 (95% CI, 1.1-1.7), 1.1 (95% CI, 1.0-1.4), 1 (reference), 1.1 (95% CI, 0.9-1.4), 1.8 (95% CI, 1.4-2.3), and 2.2 (95% CI, 1.5-3.3). Hazard ratios were lowest at a potassium of about 4.9 mmol/L. Limitations: Shorter intervals between potassium measurements would have allowed for more precise estimations. Conclusions: We observed a U-shaped relationship between serum potassium and death or KRT start among patients with incident CKD 4-5, with a nadir risk at a potassium level of 4.9 mmol/L. These findings underscore the potential importance of preventing both high and low potassium in patients with CKD 4-5. Plain-Language Summary: Abnormal potassium blood levels may increase the risk of death or kidney function decline, especially in older people with chronic kidney disease (CKD). We studied 1,714 patients aged ≥65 years with advanced CKD from the European Quality (EQUAL) study and followed them for 8 years. We found that both low and high levels of potassium were associated with an increased risk of death or start of kidney replacement therapy, with the lowest risk observed at a potassium level of 4.9 mmol/L. In patients with CKD, the focus is often on preventing high blood potassium. However, this relatively high optimum potassium level stresses the potential importance of also preventing low potassium levels in older patients with advanced CKD
siRNA inhibition of telomerase enhances the anti-cancer effect of doxorubicin in breast cancer cells
<p>Abstract</p> <p>Background</p> <p>Doxorubicin is an effective breast cancer drug but is hampered by a severe, dose-dependent toxicity. Concomitant administration of doxorubicin and another cancer drug may be able to sensitize tumor cells to the cytotoxicity of doxorubicin and lowers the therapeutic dosage. In this study, we examined the combined effect of low-dose doxorubicin and siRNA inhibition of telomerase on breast cancer cells. We found that when used individually, both treatments were rapid and potent apoptosis inducers; and when the two treatments were combined, we observed an enhanced and sustained apoptosis induction in breast cancer cells.</p> <p>Methods</p> <p>siRNA targeting the mRNA of the protein component of telomerase, the telomerase reverse transcriptase (hTERT), was transfected into two breast cancer cell lines. The siRNA inhibition was confirmed by RT-PCR and western blot on hTERT mRNA and protein levels, respectively, and by measuring the activity level of telomerase using the TRAP assay. The effect of the hTERT siRNA on the tumorigenicity of the breast cancer cells was also studied <it>in vivo </it>by injection of the siRNA-transfected breast cancer cells into nude mice.</p> <p>The effects on cell viability, apoptosis and senescence of cells treated with hTERT siRNA, doxorubicin, and the combined treatment of doxorubicin and hTERT siRNA, were examined <it>in vitro </it>by MTT assay, FACS and SA-β-galactosidase staining.</p> <p>Results</p> <p>The hTERT siRNA effectively knocked down the mRNA and protein levels of hTERT, and reduced the telomerase activity to 30% of the untreated control. <it>In vivo</it>, the tumors induced by the hTERT siRNA-transfected cells were of reduced sizes, indicating that the hTERT siRNA also reduced the tumorigenic potential of the breast cancer cells. The siRNA treatment reduced cell viability by 50% in breast cancer cells within two days after transfection, while 0.5 μM doxorubicin treatment had a comparable effect but with a slower kinetics. The combination of hTERT siRNA and 0.5 μM doxorubicin killed twice as many cancer cells, showing a cumulative effect of the two treatments.</p> <p>Conclusion</p> <p>The study demonstrated the potential of telomerase inhibition as an effective treatment for breast cancer. When used in conjunction to doxorubicin, it could potentiate the cytotoxic effect of the drug to breast cancer cells.</p
Mindfulness, self-compassion, and mindful eating in relation to fat and sugar consumption: an exploratory investigation
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