One of the most important degradation modes in CMOS technologies, the bias temperature instability (BTI) has been known since the 1960s. Already in early interpretations, charge trapping in the oxide ...was considered an important aspect of the degradation. In their 1977 paper, Jeppson and Svensson suggested a hydrogen-diffusion controlled mechanism for the creation of interface states. Their reaction-diffusion model subsequently became the dominant explanation of the phenomenon. While Jeppson and Svensson gave a preliminary study of the recovery of the degradation, this issue received only limited attention for many years. In the last decade, however, a large number of detailed recovery studies have been published, showing clearly that the reaction-diffusion mechanism is inconsistent with the data. As a consequence, the research focus shifted back toward charge trapping. Currently available advanced charge-trapping theories based on switching oxide traps are now able to explain the bulk of the experimental data. We give a review of our perspective on some selected developments in this area.
Triple negative breast cancer (TNBC) is a highly heterogeneous tumor. There is increasing evidence of the role of tumor lymphocytic immune infiltrates in this subtype of breast cancer. Robust levels ...of tumor infiltrating lymphocytes (TILs) have been associated with improved disease-free and overall survival rates in TNBC patients with and without any treatment. Recent efforts have been made to develop a standardized methodology for evaluating TILs. The presence of TILs in the breast tumor microenvironment can also predict responses not only to neoadjuvant but also to adjuvant chemotherapy treatments. High numbers of TILs correlate with increased pathological complete responses (pCR) in TNBC. TILs are prognostic and predictive of response to standard therapies; thus, the immune system appears to play an active role in a subgroup of breast cancer. There is an increasing interest in directly targeting the immune system as part of breast cancer therapy, mainly in patients with TNBC. New immune modulatory agents, including immune checkpoints inhibitors, have shown promising activity in a subgroup of metastatic TNBC. Increased programmed cell death protein 1 ligand (PD-L1) expression on the surface of TNBC provides the rationale for implementing therapeutic strategies targeting the PD-1/PD-L1 axis in TNBC. The programmed cell death protein 1 (PD-1) inhibitor pembrolizumab, and the PD-L1 inhibitor atezolizumab have shown promising results in clinical trials.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK, VSZLJ
The most abundant agrifood residues in the Mediterranean basin derive from the two traditional crops: olive trees and vineyards. They are vine shoots and leaves (both fresh and senescent leaves) ...lees, grape skins, seeds and stalk, on the one hand; olive tree leaves and olive pomace, on the other. The potential of these residues as a powerful source of well known phenols with antioxidant properties has been proved; nevertheless, there are a number of other unknown phenols together with other families of very valuable compounds that should be studied. This article constitutes a call of attention on this unexploited wealth.
•Residues from Mediterranean agriculture had not received much attention for exploitation so far.•Methods for extraction of valuable products have been developed and exposed here.•Interesting compounds for the food and nutraceutical fields have been found.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Herein, we present our results on the development of a continuous flow protocol enabling the waste minimised synthesis of relevant pharmaceuticals and natural compounds. Heterogeneous manganese ...catalytic systems have been used in combination with molecular oxygen to promote the C–H oxidative coupling of 2-aminophenols, benzenetriols and o -phenylenediamines to access a variety of 2-aminophenoxazin-3-ones ( 2a–i ) and related diaminophenazines ( 2j–k ) and purpurogallin ( 2l ) with minimal metal contamination. Making use of safe and green cyclopentyl methyl ether (CPME), this methodology allowed a fast synthesis of fully decorated molecular entities, preserving the stability of the heterogeneous catalyst which showed minimal metal leaching, with minimal waste production (low E -factor).
Obesity in children is assumed to serve as a major risk factor in pediatric obstructive sleep apnea syndrome (OSAS). However, the prevalence of OSAS in otherwise healthy obese children from the ...community is unknown.
To determine the prevalence of OSAS in obese children identified and recruited from primary care centers.
A cross-sectional, prospective, multicenter study. Spanish children ages 3-14 y with a body mass index (BMI) greater than or equal to the 95th percentile for age and sex were randomly selected, and underwent medical history, snoring, and Pediatric Sleep Questionnaire (PSQ) assessments, as well as physical examination, nasopharyngoscopy, and nocturnal polysomnography (NPSG) recordings.
Two hundred forty-eight children (54.4% males) with mean age of 10.8 ± 2.6 y were studied with a BMI of 28.0 ± 4.7 kg/m(2) corresponding to 96.8 ± 0.6 percentile when adjusted for age and sex. The mean respiratory disturbance index (RDI), obstructive RDI (ORDI), and obstructive apnea-hypopnea index (OAHI) were 5.58 ± 9.90, 5.06 ± 9.57, and 3.39 ± 8.78/h total sleep time (TST), respectively. Using ≥ 3/h TST as the cutoff for the presence of OSAS, the prevalence of OSAS ranged from 21.5% to 39.5% depending on whether OAHI, ORDI, or RDI were used.
The prevalence of obstructive sleep apnea syndrome (OSAS) in obese children from the general population is high. Obese children should be screened for the presence of OSAS. ClinicalTrials.gov identifier: NCT01322763.
Most healthy properties of fresh and black (a fermented derivative) garlic are attributed to volatile organosulfur compounds. In this research, the volatile profile of black garlic (from purple ...garlic) and its evolution along the fermentation process were evaluated using a headspace (HS) device coupled to a gas chromatography–mass spectrometry (GC–MS) arrangement. The volatile profiles of black and fresh garlic were compared by testing different heating times in the HS device. The HS–GC–MS analysis allowed identifying 51 volatile compounds that were classified into S-alk(en)yl-l-cysteine derivatives, flavor compounds and others. Significant changes in the volatile profile along fermentation allowed PCA differentiation among the process steps under study. Black and fresh garlic provided different volatile profiles, especially in flavor compounds, and presented different behaviors under heating. Especially remarkable was the evolution of sulfur volatiles.
•The volatile profile of black garlic has been studied for the first time.•The volatile profiles of black and fresh garlic have been differentiated.•The changes on the volatile profile along the fermentation have been evaluated.•The behavior of the samples when subjected to preset heating times has been studied.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Citrus fruits possess a high content of phenolic compounds; however, few studies have focused on the changes occurring during fruit growth. In this study, the changes in the concentration of 20 ...flavonoids, 4 phenolic acids, and their biosynthetic precursors phenylalanine and tyrosine have been evaluated during fruit maturation (14 weeks). Extracts from all samples, obtained by ultrasound assistance, were analyzed by liquid chromatography coupled to tandem mass spectrometry with a triple quad system (LC–QqQ MS/MS). In general, the concentration of flavanones, which represented over 70% of the studied phenols, and flavones increased during fruit growth, reaching their maximum concentration around week 12. In general, flavanols and phenolic acids exhibited their maximum concentration at week 5 and then decreasing significantly during the rest of maturation. Phenylalanine and tyrosine showed a sinuous behavior during fruit growth. Partial least-squares showed a clear differentiation among fruits belonging to different maturation stages, coumaric acid derivatives being the most influential variables on the projection.
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Biological treatments to degrade cyanide are a powerful technology for cyanide removal from industrial wastewaters. It has been previously demonstrated that the alkaliphilic bacterium Pseudomonas ...pseudoalcaligenes CECT5344 is able to use free cyanide and several metal-cyanide complexes as the sole nitrogen source. In this work, the strain CECT5344 has been used for detoxification of the different chemical forms of cyanide that are present in alkaline wastewaters from the jewelry industry. This liquid residue also contains large concentrations of metals like iron, copper and zinc, making this wastewater even more toxic. To elucidate the molecular mechanisms involved in the bioremediation process, a quantitative proteomic analysis by LC-MS/MS has been carried out in P. pseudoalcaligenes CECT5344 cells grown with the jewelry residue as sole nitrogen source. Different proteins related to cyanide and cyanate assimilation, as well as other proteins involved in transport and resistance to metals were induced by the cyanide-containing jewelry residue. GntR-like regulatory proteins were also induced by this industrial residue and mutational analysis revealed that GntR-like regulatory proteins may play a role in the regulation of cyanide assimilation in P. pseudoalcaligenes CECT5344. The strain CECT5344 has been used in a batch reactor to remove at pH 9 the different forms of cyanide present in industrial wastewaters from the jewelry industry (0.3 g/L, ca. 12 mM total cyanide, including both free cyanide and metal-cyanide complexes). This is the first report describing the biological removal at alkaline pH of such as elevated concentration of cyanide present in a heterogeneous mixture from an industrial source.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Digitaria insularis biotypes resistant to glyphosate have been detected in Brazil. Studies were carried out in controlled conditions to determine the role of absorption, translocation, metabolism, ...and gene mutation as mechanisms of glyphosate resistance in D. insularis. The susceptible biotype absorbed at least 12% more 14C-glyphosate up to 48 h after treatment (HAT) than resistant biotypes. High differential 14C-glyphosate translocation was observed at 12 HAT, so that >70% of the absorbed herbicide remained in the treated leaf in resistant biotypes, whereas 42% remained in the susceptible biotype at 96 HAT. Glyphosate was degraded to aminomethylphosphonic acid (AMPA), glyoxylate, and sarcosine by >90% in resistant biotypes, whereas a small amount of herbicide (up to 11%) was degraded by the susceptible biotype up to 168 HAT. Two amino acid changes were found at positions 182 and 310 in EPSPS, consisting of a proline to threonine and a tyrosine to cysteine substitution, respectively, in resistant biotypes. Therefore, absorption, translocation, metabolism, and gene mutation play an important role in the D. insularis glyphosate resistance.
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IJS, KILJ, NUK, PNG, UL, UM, UPUK
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