Dynamic and widespread control of poly(A) tail length during macrophage activation.

The poly(A) tail enhances translation and transcript stability, and tail length is under dynamic control during cell state transitions. Tail regulation plays essential roles in translational timing and fertilization in early development, but poly(A) tail dynamics have not been fully explored in post-embryonic systems. Here, we examined the landscape and impact of tail length control during macrophage activation. Upon activation, more than 1500 mRNAs, including proinflammatory genes, underwent distinctive changes in tail lengths. Increases in tail length correlated with mRNA levels regardless of transcriptional activity, and many mRNAs that underwent tail extension encode proteins necessary for immune function and post-transcriptional regulation. Strikingly, we found that ZFP36, whose protein product destabilizes target transcripts, undergoes tail extension. Our analyses indicate that many mRNAs undergoing tail lengthening are, in turn, degraded by elevated levels of ZFP36, constituting a post-transcriptional feedback loop that ensures transient regulation of transcripts integral to macrophage activation. Taken together, this study establishes the complexity, relevance, and widespread nature of poly(A) tail dynamics, and the resulting post-transcriptional regulation during macrophage activation.

Glycemic Trends in Patients with Thyroid Eye Disease Treated with Teprotumumab in 3 Clinical Trials.

PURPOSE: Assess incidence, severity, and glucose excursion outcomes in thyroid eye disease (TED) patients receiving the insulin-like growth factor-1 receptor inhibitor teprotumumab from 3 clinical trials. DESIGN: Analysis of pooled glycemic data over time. PARTICIPANTS: Eighty-four teprotumumab- and 86 placebo-treated active TED patients from the phase 2 and phase 3 (OPTIC) controlled clinical trials and 51 teprotumumab-treated patients from the OPTIC extension (OPTIC-X) trial. METHODS: Eight intravenous infusions were given over 21 weeks. Phase 2 serum glucose was measured at weeks 1, 4, 15, and 21, with fasting measurements at weeks 1 and 4. Serum glucose was measured at each study visit in OPTIC and OPTIC-X, with fasting measurements at weeks 1 and 4 (in patients without diabetes) or all visits (in patients with diabetes). In all studies, hemoglobin A1c (HbA1c) was measured at baseline, 12, and 24 weeks plus weeks 36 and 48 in OPTIC-X. MAIN OUTCOME MEASURES: Serum glucose and HbA1c. RESULTS: In the phase 2 and 3 studies, 9 hyperglycemic episodes occurred in 8 teprotumumab patients; mean HbA1c level increased 0.22% from baseline to week 24 (to 5.8%; range, 5.0%-7.9%) versus 0.04% in patients receiving the placebo (to 5.6%; range, 4.6%-8.1%). At study end, 78% (59/76) of teprotumumab patients and 87% (67/77) of patients receiving placebo had normoglycemic findings. Normoglycemia was maintained in 84% (57/68) of patients receiving teprotumumab and 93% (64/69) of patients receiving placebo. Among baseline prediabetic patients, 43% (3/7) remained prediabetic in both groups, and 29% (2/7) of teprotumumab patients and 14% (1/7) of patients receiving placebo had diabetic findings at week 24. OPTIC-X patients trended toward increased fasting glucose and HbA1c whether initially treated or retreated with teprotumumab. Fasting glucose commonly rose after 2 or 3 infusions and stabilized thereafter. Most hyperglycemic incidents occurred in patients with baseline prediabetes/diabetes but were controlled with medication. No evidence was found for progression or increased incidence of hyperglycemia with subsequent doses. CONCLUSIONS: Serious glycemic excursions are uncommon in patients with normoglycemia before teprotumumab therapy. Patients with controlled diabetes or impaired glucose tolerance can be treated safely if baseline screening, regular monitoring of glycemic control, and timely treatment of hyperglycemia are practiced. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Clinical and demographic predictors of buccal fat pad volume in thyroid eye disease.

PURPOSE: To understand how thyroid eye disease (TED) impacts buccal fat pad (BFP) volume. METHODS: In this cohort study, computed tomography (CT) scans and charts of adult patients with and without TED were obtained from an institutional database. The primary outcome was BFP volume in cubic centimeters. Three independent, blinded observers analyzed scans using Horos, a free, open-source medical image viewing software. Bivariate and multivariable analyses were performed. We determined sample size using an effect size based on published reports of the minimum amount of fat excision needed to notice a clinical difference. Equivalence testing against upper and lower bounds set by the same effect size was conducted to assess practical significance of the results. RESULTS: Our sample was sufficient to detect a difference as large as 1.5cc with 95% power. 72 scans were included in our study, 24 TED patients and 48 controls. Mean BFP volume was not statistically different between TED patients and controls (3.96 cc vs 4.06 cc, p = .778). Analysis of covariance adjusting for relevant patient factors (age, sex, and BMI) also failed to find a significant difference between groups. Equivalence testing was significant (p < .001) and revealed the observed difference between groups was less than any clinically meaningful difference. For an effect size of 1.5cc, the data suggests there is a 5% risk of a false negative. CONCLUSIONS: TED was not associated with a significant difference in BFP volume, suggesting that the BFP is spared from TED-related soft-tissue expansion.

Neurodiversity in the Minds of Students: From Perception to Campus Programming.

Neurodiversity is a social justice movement at the nexus of neuroscience, academia, and public policy. A contemporary view of neurodiversity is one that embraces neurological differences, encompassing all "neurotypes," including more specific identifiers like autistic or dyslexic. The goal of this study was to investigate student awareness and perception of neurodiversity since they are the next generation of public policy makers. Students enrolled in Introduction to Behavioral Neuroscience (N=146) were exposed to different information sources (popular, academic, TED talk, or choose/find their own) on the topic of neurodiversity. They then wrote a paper where they summarized: a) the information source used, b) their ideas to better support a neurodiverse society, and c) their opinions on aspects of neurodiversity. Several important findings emerged. First, 64% of the sample had never heard of the term neurodiversity; this class was their first exposure to it. Second, students conducting their own searches on neurodiversity had the highest level of optimism (p < 0.05) that society was ready to accept neurodiversity. Students identified even higher rates of receptivity (85%) amongst their friends. Third, student ideas to advance neurodiversity were organized into more salient categories for campuses to consider. Our findings challenge neuroscience programs to consider their role in providing "first exposure" opportunities to students in the diversity, equity, and inclusion realm, especially in areas directly related to our field. We also discuss the growing relevance of neurodiversity in research and academia and offer programming possibilities to enhance neurodiversity awareness and support on college campuses.

[Bony orbital decompression in thyroid eye disease]. / Kostnaya dekompressiya orbity pri endokrinnoi oftal'mopatii.

This article summarizes the results of research on the morphological and functional features of different types of orbital bone decompression in thyroid eye disease (TED) and presents an analysis of surgical anatomy of the lateral orbital wall in the context of performing deep lateral bone decompression of the orbit was carried out. The study includes an analysis of the results of orbital bone decompression with resection of the greater wing of the sphenoid bone using ultrasound osteodestructor in comparison with osteodestruction using a high-speed drill, description of transethmoidal orbital decompression with endonasal access both as a single method of surgical treatment of TED and in combination with lateral bone decompression of the orbit, including the advantages and disadvantages of the method, and presents a morphological description of the pathological changes in the medial orbital wall bone fragments obtained during endonasal transethmoidal orbital decompression in patients with TED.

Short-term effect of retirement on health: Evidence from nonparametric fuzzy regression discontinuity design.

We estimate the short-term effect of retirement on health in the US using the Health and Retirement Study survey. We use the nonparametric fuzzy regression discontinuity design to avoid assuming any functional form on the age-health profile and minimize potential bias in identifying the causal effect of retirement on health status in the short term. Estimates indicate an 8% decline in the cognitive functioning score of retirees and a 28% increase in the CESD depression scale. The likelihood of being in good health status declined by 16%. The transition from working to retirement has more significant negative impacts on males than females. In addition, retirement has more considerable adverse effects on less-educated individuals compared to high-educated individuals. The short-term effects of retirement on health are consistent and robust across different bandwidths, weighting kernel functions, and age-profile specifications. Moreover, the Treatment Effect Derivative test results highly support the external validity of the nonparametric estimates of the retirement effect on health.

Emergency Management in the Event of Radiological Dispersion in an Urban Environment.

Dispersion of a radiological source is a complex scenario in terms of first response, especially when it occurs in an urban environment. The authors in this paper designed, simulated, and analyzed the data from two different scenarios with the two perspectives of an unintentional fire event and a Radiological Dispersal Device (RDD) intentional explosion. The data of the simulated urban scenario are taken from a real case of orphan sources abandoned in a garage in the center of the city of Milan (Italy) in 2012. The dispersion and dose levels are simulated using Parallel Micro Swift Spray (PMSS) software, which takes into account the topographic and meteorological information of the reference scenarios. Apart from some differences in the response system of the two scenarios analyzed, the information provided by the modeling technique used, compared to other models not able to capture the actual urban and meteorological contexts, make it possible to modulate a response system that adheres to the real impact of the scenario. The authors, based on the model results and on the evidence provided by the case study, determine the various countermeasures to adopt to mitigate the impact for the population and to reduce the risk factors for the first responders.

A Microporous Zn(bdc)(ted)0.5 with Super High Ethane Uptake for Efficient Selective Adsorption and Separation of Light Hydrocarbons.

Separating light hydrocarbons (C2H6, C3H8, and C4H10) from CH4 is challenging but important for natural gas upgrading. A microporous metal-organic framework, Zn(bdc)(ted)0.5, based on terephthalic acid (bdc) and 1,4-diazabicyclo[2.2.2]octane (ted) ligands, is synthesized and characterized through various techniques, including powder X-ray diffraction (PXRD), scanning electron microscopy (SEM), thermogravimetric analysis (TGA), and porosity analysis. The adsorption isotherms of light hydrocarbons on the material are measured and the isosteric adsorption heats of CH4, C2H6, C3H8, and C4H10 are calculated. The prediction of C2-4/C1 adsorption selectivities is accomplished using ideal adsorbed solution theory (IAST). The results indicate that the material exhibits exceptional characteristics, including a Brunauer-Emmett-Teller (BET) surface area of 1904 m2/g and a pore volume of 0.73 cm3/g. Notably, the material demonstrates remarkable C2H6 adsorption capacities (4.9 mmol/g), while CH4 uptake remains minimal at 0.4 mmol/g at 298 K and 100 kPa. These findings surpass those of most reported MOFs, highlighting the material's outstanding performance. The isosteric adsorption heats of C2H6, C3H8, and C4H10 on the Zn(bdc)(ted)0.5 are higher than CH4, suggesting a stronger interaction between C2H6, C3H8, and C4H10 molecules and Zn(bdc)(ted)0.5. The molecular simulation reveals that Zn(bdc)(ted)0.5 prefers to adsorb hydrocarbon molecules with richer C-H bonds and larger polarizability, which results in a stronger dispersion force generated by an adsorbent-adsorbate induced polarization effect. Therefore, the selectivity of C4H10/CH4 is up to 180 at 100 kPa, C3H8/CH4 selectivity is 67, and the selectivity of C2H6/CH4 is 13, showing a great potential for separating C2-4 over methane.

Identifying and optimizing human endometrial gene expression signatures for endometrial dating.

STUDY QUESTION: What are the key considerations for developing an enhanced transcriptomic method for secretory endometrial tissue dating? SUMMARY ANSWER: Multiple gene expression signature combinations can serve as biomarkers for endometrial dating, but their predictive performance is variable and depends on the number and identity of the genes included in the prediction model, the dataset characteristics and the technology employed for measuring gene expression. WHAT IS KNOWN ALREADY: Among the new generation of transcriptomic endometrial dating (TED) tools developed in the last decade, there exists variation in the technology used for measuring gene expression, the gene makeup and the prediction model design. A detailed study, comparing prediction performance across signatures for understanding signature behaviour and discrepancies in gene content between them, is lacking. STUDY DESIGN, SIZE, DURATION: A multicentre prospective study was performed between July 2018 and October 2020 at five different centres from the same group of clinics (Spain). This study recruited 281 patients and finally included in the gene expression analysis 225 Caucasian patients who underwent IVF treatment. After preprocessing and batch effect filtering, gene expression measurements from 217 patients were combined with artificial intelligence algorithms (support vector machine, random forest and k-nearest neighbours) allowing evaluation of different prediction models. In addition, secretory-phase endometrial transcriptomes from gene expression omnibus (GEO) datasets were analysed for 137 women, to study the endometrial dating capacity of genes independently and grouped by signatures. This provided data on the consistency of prediction across different gene expression technologies and datasets. PARTICIPANTS/MATERIALS, SETTING, METHODS: Endometrial biopsies were analysed using a targeted TruSeq (Illumina) custom RNA expression panel called the endometrial dating panel (ED panel). This panel included 301 genes previously considered relevant for endometrial dating as well as new genes selected for their anticipated value in detecting the secretory phase. Final samples (n = 217) were divided into a training set for signature discovery and an independent testing set for evaluation of predictive performance of the new signature. In addition, secretory-phase endometrial transcriptomes from GEO were analysed for 137 women to study endometrial dating capacity of genes independently and grouped by signatures. Predictive performance among these signatures was compared according to signature gene set size. MAIN RESULTS AND THE ROLE OF CHANCE: Testing of the ED panel allowed development of a model based on a new signature of 73 genes, which we termed 'TED' and delivers an enhanced tool for the consistent dating of the secretory phase progression, especially during the mid-secretory endometrium (3-8 days after progesterone (P) administration (P + 3-P + 8) in a hormone replacement therapy cycle). This new model showed the best predictive capacity in an independent test set for staging the endometrial tissue in the secretory phase, especially in the expected window of implantation (average of 114.5 ± 7.2 h of progesterone administered; range in our patient population of 82-172 h). Published sets of genes, in current use for endometrial dating and the new TED genes, were evaluated in parallel in whole-transcriptome datasets and in the ED panel dataset. TED signature performance was consistently excellent for all datasets assessed, frequently outperforming previously published sets of genes with a smaller number of genes for dating the endometrium in the secretory phase. Thus, this optimized set exhibited prediction consistency across datasets. LARGE SCALE DATA: The data used in this study is partially available at GEO database. GEO identifiers GSE4888, GSE29981, GSE58144, GSE98386. LIMITATIONS, REASONS FOR CAUTION: Although dating the endometrial biopsy is crucial for investigating endometrial progression and the receptivity process, further studies are needed to confirm whether or not endometrial dating methods in general are clinically useful and to guide the specific use of TED in the clinical setting. WIDER IMPLICATIONS OF THE FINDINGS: Multiple gene signature combinations provide adequate endometrial dating, but their predictive performance depends on the identity of the genes included, the gene expression platform, the algorithms used and dataset characteristics. TED is a next-generation endometrial assessment tool based on gene expression for accurate endometrial progression dating especially during the mid-secretory. STUDY FUNDING/COMPETING INTEREST(S): Research funded by IVI Foundation (1810-FIVI-066-PD). P.D.-G. visiting scientist fellowship at Oxford University (BEFPI/2010/032) and Josefa Maria Sanchez-Reyes' predoctoral fellowship (ACIF/2018/072) were supported by a program from the Generalitat Valenciana funded by the Spanish government. A.D.-P. is supported by the FPU/15/01398 predoctoral fellowship from the Ministry of Science, Innovation and Universities (Spanish Government). D.W. received support from the NIHR Oxford Biomedical Research Centre. The authors do not have any competing interests to declare.

Advances in the Treatment of Thyroid Eye Disease Associated Extraocular Muscle Myopathy and Optic Neuropathy.

PURPOSE OF REVIEW: To review emerging treatments for thyroid eye disease (TED) associated extraocular muscle myopathy and dysthyroid optic neuropathy (DON). RECENT FINDINGS: Emerging targeted biologic therapies may alter the disease course in TED. Teprotumumab, a type I insulin-like growth factor receptor inhibitor, is the most recent addition to the treatments available for TED-associated extraocular muscle myopathy causing diplopia. Small studies also suggest a potential therapeutic benefit for DON. Various recent studies have also expanded our knowledge on conventional TED therapies. The therapeutic landscape of TED and its sequelae has evolved in recent years. New targeted therapies have the potential to reduce the extraocular muscle and orbital volume expansion which can lead to diplopia and vision loss from optic nerve compression. Longer term efficacy and durability data is needed to determine the role biologics, such as teprotumumab, should play in the treatment of TED patients compared to the current standard of care.

Clinical profile of 80-year-old and older thyroid eye disease patients.

PURPOSE: Thyroid eye disease (TED), an autoimmune orbital disorder, follows a time-of-onset bimodal peak: 40-44 and 60-64 years for women, 45-49 and 65-69 years for men. TED, however, can also commence in old age. The study's purpose was to evaluate TED in octo- and nonagenarians. METHODS: Medical records of 19 ≥ 80 years geriatric patients at time of diagnosis were compared to 122 TED patients, aged 20-79. A second analysis was performed after subdividing the control group into two age groups, ≤ 40 ("young group," 16 patients) and 41-79 years ("middle-aged group," 106 patients). RESULTS: The geriatric group's mean age was 84 years (80-94), 11 males and 8 females. Mean follow-up time was 16 months. Compared to the controls, the geriatric patients smoked less (p = 0.012), were more often hypothyroid (p = 0.019), and had concurrent myasthenia gravis (p = 0.02) at time of diagnosis. Diplopia was the most common presenting symptom among the elderly (p = 0.005) and proptosis among the controls, specifically the young group (p = 0.027). Bilateral signs were more common among seniors (p = 0.049). Optic neuropathy was diagnosed in 10% of the geriatric group (2/19) and 11% of middle-aged group (12/106), all being resolved after steroids or orbital decompression. Active disease (clinical activity score (CAS) score = > 3) was more common among the middle-aged group (p = 0.024) while the geriatric patients tended towards higher TED severity grades. Orbital decompression and eyelid repositioning surgeries were more common among the middle-aged group. Strabismus surgeries were more common among seniors. CONCLUSIONS: TED among octo- and nonagenarians has unique patterns, with different demographic features, more exposed to diplopia, hypothyroidism, association with myasthenia gravis, and bilateral involvement. Special attention should be given when medically managing this subgroup.

Cloning of Maize TED Transposon into Escherichia coli Reveals the Polychromatic Sequence Landscape of Refractorily Propagated Plasmids.

MuDR, the founder member of the Mutator superfamily and its MURA transcripts, has been identified as toxic sequences to Escherichia coli (E. coli), which heavily hindered the elucidation of the biochemical features of MURA transposase and confined the broader application of the Mutator system in other organisms. To harness less constrained systems as alternatives, we attempted to clone TED and Jittery, two recently isolated autonomous Mutator-like elements (MULEs) from maize, respectively. Their full-length transcripts and genomic copies are successfully cloned when the incubation time for bacteria to recover from heat shock is extended appropriately prior to plating. However, during their proliferation in E. coli, TED transformed plasmids are unstable, as evidenced by derivatives from which frameshift, deletion mutations, or IS transposon insertions are readily detected. Our results suggest that neither leaky expression of the transposase nor the presence of terminal inverse repeats (TIRs) are responsible for the cloning barriers, which were once ascribed to the presence of the Shine-Dalgarno-like sequence. Instead, the internal sequence of TED (from 1250 to 2845 bp), especially the exons in this region, was the most likely causer. The findings provide novel insights into the property and function of the Mutator superfamily and shed light on the dissection of toxic effects on cloning from MULEs.

Treatment of High-Polyphenol-Content Waters Using Biotechnological Approaches: The Latest Update.

Polyphenols and their intermediate metabolites are natural compounds that are spread worldwide. Polyphenols are antioxidant agents beneficial for human health, but exposure to some of these compounds can be harmful to humans and the environment. A number of industries produce and discharge polyphenols in water effluents. These emissions pose serious environmental issues, causing the pollution of surface or groundwater (which are used to provide drinking water) or harming wildlife in the receiving ecosystems. The treatment of high-polyphenol-content waters is mandatory for many industries. Nowadays, biotechnological approaches are gaining relevance for their low footprint, high efficiency, low cost, and versatility in pollutant removal. Biotreatments exploit the diversity of microbial metabolisms in relation to the different characteristics of the polluted water, modifying the design and the operational conditions of the technologies. Microbial metabolic features have been used for full or partial polyphenol degradation since several decades ago. Nowadays, the comprehensive use of biotreatments combined with physical-chemical treatments has enhanced the removal rates to provide safe and high-quality effluents. In this review, the evolution of the biotechnological processes for treating high-polyphenol-content water is described. A particular emphasis is given to providing a general concept, indicating which bioprocess might be adopted considering the water composition and the economic/environmental requirements. The use of effective technologies for environmental phenol removal could help in reducing/avoiding the detrimental effects of these chemicals. In addition, some of them could be employed for the recovery of beneficial ones.

Retinal vascularity, nerve fiber, and ganglion cell layer thickness in thyroid eye disease on optical coherence tomography angiography.

PURPOSE: To compare the retinal vascularity, peripapillary vascularity, nerve fiber layer thickness and ganglion cell layer thickness between active, inactive thyroid eye disease (TED) and healthy eyes. METHODS: Retrospective comparative cross-sectional cohort study. Patients with TED, active and inactive on the VISA score, and healthy eyes were included. All patients underwent optical coherence tomography angiography with detailed demographic and clinical data capture. Using automated software, retinal and peripapillary vascularity index, nerve fiber layer thickness, and ganglion cell layer thickness were calculated and were compared between the groups. RESULTS: Twenty-four eyes with active TED, 102 eyes with inactive TED and 52 healthy eyes were included. Independent sample t test was used to compare parametric data and Mann-Whitney test to compare non-parametric data. The age and gender were comparable across groups. The peripapillary vascularity index (26.82 ± 4.13 versus 34.92 ± 5.08, p = .002) and the macular vascularity index (20.32 ± 2.5 versus 31.21 ± 3.89, p < .0001) were reduced in active TED eyes versus inactive eyes. Macular vascularity index was comparable in the inactive versus the healthy eyes. The RNFL thickness was increased in the active TED eyes versus the inactive eyes (45.11 ± 18.3 versus 35.55 ± 7, p = .03) and active versus healthy eyes (45.11 ± 18.3 versus 36.28 ± 7.89, p = .03). Ganglion cell layer thickness between all three groups was comparable. CONCLUSION: Decrease in peripapillary and macular vascular density and increase in RNFL thickness are seen in active TED compared to inactive TED and healthy eyes. In disease inactivity, these parameters are comparable to healthy eyes.

Choroidal vascularity index in thyroid eye disease: comparison with controls and application in diagnosing non-inflammatory active disease.

PURPOSE: To report the differences in choroidal vascularity index (CVI) in thyroid eye disease (TED) and normals and its discriminatory value for differentiating various stages of TED. METHODS: Prospective, cross-sectional, non-interventional imaging study. Ninety-four eyes of 54 patients were included and divided into 5 groups - normal controls (C), inactive TED (I), active TED (A), non-inflammatory active TED (NIA) and systemic hyperthyroid disorder but no TED (SYS). Choroidal images were acquired using the swept-source optical coherence tomography and the choroid was binarized to calculate the CVI. RESULTS: Ninety-four eyes were included. Mean age was 44.52 ± 10.02 years (median 46 years, range 19-65 years). Mean IOP was 16.1 ± 3.37 mm Hg (median 16 mm Hg, range 16-24 mm Hg). Mean Spherical equivalent (SE) was -0.08 ± 1.86 diopters (median 0, range -2.5 to +2.25). Intra-rater agreement was 0.84 (p < 0.001). Inter-rater agreement was noted to be 0.85 (p < 0.001) for consistency and 0.77 (p < 0.001) for absolute agreement. CVI in the A group was 70.11 ± 3.38% and in the NIA group was 69.32 ± 3.5%. Both were comparable to each other and significantly higher than the C, I and SYS groups (p < 0.001). Multiple regression showed that the Clinical Activity Score (CAS) had a positive effect and spheroequivalent had a negative effect on the CVI. At CVI of 66.83%, active TED can be diagnosed with sensitivity of 91.67% and specificity of 82.14%                 . CONCLUSIONS: CVI is significantly higher in active TED and NIA TED compared to other groups. It has a good value in differentiating the non-inflammatory active TED eyes from the inactive eyes.

Organic Markers of Tire and Road Wear Particles in Sediments and Soils: Transformation Products of Major Antiozonants as Promising Candidates.

Tire and road wear particles (TRWPs) are one of the main sources of particulate traffic emissions, but measured data on TRWP contents in the environment are scarce. This study aims at identifying organic compounds suitable as quantitative markers for TRWPs by a tiered multistep selection process involving nontarget screening and subsequent identification by liquid-chromatography high-resolution mass spectrometry. Starting from several thousands of signals recorded in the extract of tire particles, the rigorous selection process considered source specificity, tendency of leaching, analytical sensitivity and precision, and stability during aging. It led to three transformation products of N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine (6-PPD) as the most suitable marker candidates: N-formyl-6-PPD, hydroxylated N-1,3-dimethylbutyl-N-phenyl quinone diimine, and 6-PPD-quinone. A linear response in standard addition experiments with tire particles and the correlation with TRWP contents in a diverse set of environmental samples imply that these compounds are promising candidates as markers for the quantification of TRWPs. Organic markers for TRWP contents in the environment would allow TRWP quantification with the traditional tandem MS (LC-MS/MS) equipment of an organic trace analytical laboratory and, thus, allow easy generation of data on TRWP occurrence in sediments and soils and other environmental matrices.

18 F-FDG-PET/MRI in patients with Graves' orbitopathy.

PURPOSE: Currently, therapeutic management of patients with Graves' orbitopathy (GO) relies on clinical assessments and MRI. However, monitoring of inflammation remains difficult since external inflammatory signs do not necessarily represent the orbital disease activity. Therefore, we aimed to evaluate the diagnostic value of 18F-FDG-PET/MRI to assess the inflammation of GO patients. METHODS: Enrolled patients with new onset of GO underwent ophthalmological examinations to evaluate the activity (CAS) and severity of GO (NOSPECS), as well as an 18F-FDG-PET/MRI (Siemens Biograph mMR) with dual time point imaging (immediately post-injection and 60 min p.i.). A subset of PET parameters including maximum standardized uptake value (SUVmax), metabolic target volume (MTV), and total lesion glycolysis (TLG) were obtained separately per eye and per extraocular eye muscle (EOM). EOM thickness was measured on the co-registered MRI. RESULTS: Of 14 enrolled patients, three showed mild, seven moderate-to-severe, and four sight-threatening GO. Patients with severe GO showed statistically significant higher TLG than patients with mild GO (p = 0.02) and higher MTV than patients with mild (p = 0.03) and moderate (p = 0.04) GO. Correlation between NOSPECS on one hand and MTV and TLG on the other was significant (R2 = 0.49-0.61). CONCLUSION: TLG and MTV derived from FDG-PET appear to be good discriminators for severe vs. mild-to-moderate GO and show a significant correlation with NOSPECS. As expected, PET parameters of individual eye muscles were not correlated with associated eye motility, since fibrosis, and not inflammation, is mainly responsible for restricted motility. In conclusion, 18F-FDG-PET/MRI can be used for assessment of GO inflammation.

On the Frequency Carrier Offset and Symbol Timing Estimation for CCSDS 131.2-B-1 High Data-Rate Telemetry Receivers.

In recent years there have been significant developments in satellite transmitter technology to follow the rapid innovation of sensors on-board new satellites. The CCSDS 131.2-B-1 standard for telemetry downlink, released in 2012, is part of the next generation of standards that aims to support the increased data-rate caused by these improvements in resolution. As a result of its relative novelty, this standard currently lacks in-depth analysis by researchers, but it is also strongly supported by the European Space Agency (ESA) for future missions. For these reasons, it seems important to evaluate how major receiver sub-components, such as timing recovery and carrier frequency correction, can be designed and implemented in new receivers that support this standard. The timing error detectors (TED) and frequency error detectors (FED) were therefore studied on the specific peculiarities of CCSDS 131.2-B-1 in its usual environment of Low Earth Orbit (LEO). Estimators have been evaluated highlighting performances, trade-offs and peculiarities of each one with respect to corresponding architectural choices. Finally, a receiver architecture derived from the paper considerations is proposed in the aim of supporting very different mission scenarios. Specifically, the realized architecture employs a parallel feedforward estimator for the timing recovery section and a novel multi-algorithm feedback frequency correction loop to efficiently cover both low symbol rates (5 Mbaud) and high data-rates (up to 500 Mbaud). This solution represents a good trade-off to support these scenarios in a very compact footprint by pushing the clock frequency to the FPGA limit. The FPGA resources occupation on a Zynq Ultrascale+ RFSoC XCZU28DR FPGA is 5202 LUT, 4851 FF, 5 BRAM, and 21 DSP for the timing recovery part, while the frequency recovery section occupies 1723 LUT, 1511 FF, 2.5 BRAM and 32 DSP.

The Bluegrass corpus: Audio-visual stimuli to investigate foreign accents.

The Bluegrass corpus includes sentences from 40 pairs of speakers. Participants from the Bluegrass Region rated one speaker from each pair as having a native North American English accent and the other as having a foreign accent (Experiment 1). Furthermore, speakers within each pair looked very similar in appearance, in that participants rated them similarly likely to speak with a foreign accent (Experiment 2). For each speaker we selected eight sentences based on participants' ratings of difficulty (Experiment 3). The final corpus includes a selection of 640 sentences (80 speakers, 8 stimuli per speaker) freely available through the Open Science Framework. Each sentence can be downloaded in different formats (text, audio, video) so researchers can investigate how audio-visual information influences language processing. Researchers can contribute to the corpus by validating the stimuli with new populations, selecting additional sentences, or finding new TED videos featuring appropriate speakers to answer their research questions.

Statistical Inference for Ergodic Algorithmic Model (EAM), Applied to Hydrophobic Hydration Processes.

The thermodynamic properties of hydrophobic hydration processes can be represented in probability space by a Dual-Structure Partition Function {DS-PF} = {M-PF} · {T-PF}, which is the product of a Motive Partition Function {M-PF} multiplied by a Thermal Partition Function {T-PF}. By development of {DS-PF}, parabolic binding potential functions α) RlnKdual = (-ΔG°dual/T) ={f(1/T)*g(T)} and ß) RTlnKdual = (-ΔG°dual) = {f(T)*g(lnT)} have been calculated. The resulting binding functions are "convoluted" functions dependent on the reciprocal interactions between the primary function f(1/T) or f(T) with the secondary function g(T) or g(lnT), respectively. The binding potential functions carry the essential thermodynamic information elements of each system. The analysis of the binding potential functions experimentally determined at different temperatures by means of the Thermal Equivalent Dilution (TED) principle has made possible the evaluation, for each compound, of the pseudo-stoichiometric coefficient ±ξw, from the curvature of the binding potential functions. The positive value indicates convex binding functions (Class A), whereas the negative value indicates concave binding function (Class B). All the information elements concern sets of compounds that are very different from one set to another, in molecular dimension, in chemical function, and in aggregation state. Notwithstanding the differences between, surprising equal unitary values of niche (cavity) formation in Class A <Δhfor>A = -22.7 ± 0.7 kJ·mol-1·ξw-1 sets with standard deviation σ = ±3.1% and <Δsfor>A = -445 ± 3J·K-1·mol-1·ξw-1J·K-1·mol-1·ξw-1 with standard deviation σ = ±0.7%. Other surprising similarities have been found, demonstrating that all the data analyzed belong to the same normal statistical population. The Ergodic Algorithmic Model (EAM) has been applied to the analysis of important classes of reactions, such as thermal and chemical denaturation, denaturation of proteins, iceberg formation or reduction, hydrophobic bonding, and null thermal free energy. The statistical analysis of errors has shown that EAM has a general validity, well beyond the limits of our experiments. Specifically, the properties of hydrophobic hydration processes as biphasic systems generating convoluted binding potential functions, with water as the implicit solvent, hold for all biochemical and biological solutions, on the ground that they also are necessarily diluted solutions, statistically validated.