Master-equation approach to the study of phase-change processes in data storage media

We study the dynamics of crystallization in phase-change materials using a master-equation approach in which the state of the crystallizing material is described by a cluster size distribution function. A model is developed using the thermodynamics of the processes involved and representing the clusters of size two and greater as a continuum but clusters of size one (monomers) as a separate equation. We present some partial analytical results for the isothermal case and for large cluster sizes, but principally we use numerical simulations to investigate the model. We obtain results that are in good agreement with experimental data and the model appears to be useful for the fast simulation of reading and writing processes in phase-change optical and electrical memories

Ubiquitin-Specific Protease 8 Mutant Corticotrope Adenomas Present Unique Secretory and Molecular Features and Shed Light on the Role of Ubiquitylation on ACTH Processing

Background: Somatic mutations in the ubiquitin-specific protease 8 (USP8) gene have recently been shown to occur in ACTH-secreting pituitary adenomas, thus calling attention to the ubiquitin system in corticotrope adenomas. Objectives: Assess the consequences of USP8 mutations and establish the role of ubiquitin on ACTH turnover in human ACTH-secreting pituitary adenomas. Methods: USP8 mutation status was established in 126 ACTH-secreting adenomas. Differences in ACTH secretion and POMC expression from adenoma primary cultures and in microarray gene expression profiles from archival specimens were sought according to USP8 sequence. Ubiquitin/ACTH coimmunoprecipitation and incubation with MG132, a proteasome inhibitor, were performed in order to establish whether ubiquitin plays a role in POMC/ACTH degradation in corticotrope adenomas. Results: USP8 mutations were identified in 29 adenomas (23%). Adenomas presenting USP8 mutations secreted greater amounts of ACTH and expressed POMC at higher levels compared to USP wild-type specimens. USP8 mutant adenomas were also more sensitive to modulation by CRH and dexamethasone in vitro. At microarray analysis, genes associated with endosomal protein degradation and membrane components were downregulated in USP8 mutant adenomas as were AVPR1B, IL11RA, and PITX2. Inhibition of the ubiquitin-proteasome pathway increased ACTH secretion and POMC itself proved a target of ubiquitylation, independently of USP8 sequence status. Conclusions: Our study has shown that USP8 mutant ACTH-secreting adenomas present a more "typical" corticotrope phenotype and reduced expression of several genes associated with protein degradation. Further, ubiquitylation is directly involved in intracellular ACTH turnover, suggesting that the ubiquitin-proteasome system may represent a target for treatment of human ACTH-secreting adenomas

Targeted Next-Generation Sequencing Indicates a Frequent Oligogenic Involvement in Primary Ovarian Insufficiency Onset

Primary ovarian insufficiency (POI) is one of the major causes of female infertility associated with the premature loss of ovarian function in about 3.7% of women before the age of 40. This disorder is highly heterogeneous and can manifest with a wide range of clinical phenotypes, ranging from ovarian dysgenesis and primary amenorrhea to post-pubertal secondary amenorrhea, with elevated serum gonadotropins and hypoestrogenism. The ovarian defect still remains idiopathic in some cases; however, a strong genetic component has been demonstrated by the next-generation sequencing (NGS) approach of familiar and sporadic POI cases. As recent evidence suggested an oligogenic architecture for POI, we developed a target NGS panel with 295 genes including known candidates and novel genetic determinants potentially involved in POI pathogenesis. Sixty-four patients with early onset POI (range: 10–25 years) of our cohort have been screened with 90% of target coverage at 50×. Here, we report 48 analyzed patients with at least one genetic variant (75%) in the selected candidate genes. In particular, we found the following: 11/64 patients (17%) with two variants, 9/64 (14%) with three variants, 9/64 (14%) with four variants, 3/64 (5%) with five variants, and 2/64 (3%) with six variants. The most severe phenotypes were associated with either the major number of variations or a worse prediction in pathogenicity of variants. Bioinformatic gene ontology analysis identified the following major pathways likely affected by gene variants: 1) cell cycle, meiosis, and DNA repair; 2) extracellular matrix remodeling; 3) reproduction; 4) cell metabolism; 5) cell proliferation; 6) calcium homeostasis; 7) NOTCH signaling; 8) signal transduction; 9) WNT signaling; 10) cell death; and 11) ubiquitin modifications. Consistently, the identified pathways have been described in other studies dissecting the mechanisms of folliculogenesis in animal models of altered fertility. In conclusion, our results contribute to define POI as an oligogenic disease and suggest novel candidates to be investigated in patients with POI

Monetary reward increases attentional effort in the flanker task

An important question is whether monetary reward can increase attentional effort in order to improve performance. Up to now, evidence for a positive answer is weak. Therefore, in the present study, the flanker task was used to examine this question further. Participants had to respond sooner than a certain deadline in a flanker task. One group of participants received a performance-contingent monetary reward, whereas the other group earned a fixed amount of money. As a result, monetary reward significantly improved performance in comparison with the control group. The analysis of speed accuracy trade-off functions revealed that monetary reward increased attentional effort, leading to an enhanced quality of stimulus coding. Little evidence was found that reward also improved selective spatial attention

Molecular Landscape and Association with Crohn Disease of Poorly Cohesive Carcinomas of the Nonampullary Small Bowel

Objectives: Poorly cohesive carcinomas (PCCs) are neoplasms defined by a predominantly dyshesive growth pattern with single cell or cord-like stromal infiltration. The -distinctive clinicopathologic and prognostic features of small bowel PCCs (SB-PCCs) in comparison with conventional-type small intestinal adenocarcinomas have only recently been characterized. However, as SB-PCCs' genetic profile is still unknown, we aimed to analyze the molecular landscape of SB-PCCs. Methods: A next-generation sequencing analysis through Trusight Oncology 500 on a series of 15 nonampullary SB-PCCs was performed. Results: The most frequently found gene alterations were TP53 (53%) and RHOA (13%) mutations and KRAS amplification (13%), whereas KRAS, BRAF, and PIK3CA mutations were not identified. Most SB-PCCs (80%) were associated with Crohn disease, including both RHOA-mutated SB-PCCs, which featured a non-SRC-type histology, and showed a peculiar appendiceal-type, low-grade goblet cell adenocarcinoma (GCA)-like component. Rarely, SB-PCCs showed high microsatellite instability, mutations in IDH1 and ERBB2 genes, or FGFR2 amplification (one case each), which are established or promising therapeutic targets in such aggressive cancers. Conclusions: SB-PCCs may harbor RHOA mutations, which are reminiscent of the diffuse subtype of gastric cancers or appendiceal GCAs, while KRAS and PIK3CA mutations, commonly involved in colorectal and small bowel adenocarcinomas, are not typical of such cancers

Nine-year nationwide environmental surveillance of hepatitis E virus in urban wastewaters in Italy (2011–2019)

Hepatitis E virus (HEV) is an emerging causative agent of acute hepatitis worldwide. To provide insights into the epidemiology of HEV in Italy, a large-scale investigation was conducted into urban sewage over nine years (2011–2019), collecting 1374 sewage samples from 48 wastewater treatment plants located in all the 20 regions of Italy. Broadly reactive primers targeting the ORF1 and ORF2 regions were used for the detection and typing of HEV, followed by Sanger and next generation sequencing (NGS). Real-time RT-qPCR was also used to attempt quantification of positive samples. HEV RNA detection occurred in 74 urban sewage samples (5.4%), with a statistically significant higher frequency (7.1%) in central Italy. Fifty-six samples were characterized as G3 strains and 18 as G1. While the detection of G3 strains occurred in all the surveillance period, G1 strains were mainly detected in 2011–2012, and never in 2017–2019. Typing was achieved in 2 samples (3f subtype). Viral concentrations in quantifiable samples ranged from 1.2 × 103 g.c./L to 2.8 × 104 g.c./L. Our results suggest the considerable circulation of the virus in the Italian population, despite a relatively small number of notified cases, a higher occurrence in central Italy, and a noteworthy predominance of G3 strains

Primary pulmonary nodular Amyloidosis

Primary nodular amyloidosis of the lung is an uncommon manifestation. The disease runs a benign course, but offers diagnostic problems due to non-specific radiological features entering the big field of the solitary nodule. We describe the case of a 60 year old man with multiple nodules on the left lung operated on diagnostic and therapeutic video-assisted thoracoscopy and discuss the possibilities, if any, of suspecting such a disease through radiologic characteristics along with findings from the patient’s history, physical examination and laboratory tests

Infestação de plantas daninhas após diferentes coberturas invernais em espaçamentos e populações variados na cultura do milho.

O uso de técnicas integradas para o manejo de plantas daninhas torna-se uma ferramenta para adoção de manejo mais sustentável

Accelerated deployment of nanostructured hydrotreating catalysts. Final CRADA Report.

Nanomanufacturing offers an opportunity to create domestic jobs and facilitate economic growth. In response to this need, U.S. Department of Energy, Office of Energy Efficiency and Renewable Energy issued a Research Call to develop nanomanufacturing capabilities at the National Laboratories. High performance catalysts represent a unique opportunity to deploy nanomanufacturing technologies. Re-refining of used lube oil offers an opportunity to create manufacturing jobs and decrease dependence on imported petroleum. Improved catalysts are required to produce a better quality product, decrease environmental impact, extend catalyst life, and improve overall economics of lube oil re-refining. Argonne National Laboratory (Argonne) in cooperation with Universal Lubricants, Inc. (ULI) and Chemical Engineering Partners (CEP) have carried out a Cooperative Research and Development Agreement (CRADA) to prepare nanostructured hydrotreating catalysts using atomic layer deposition (ALD) to exhibit superior performance for the re-refining of used lube oil. We investigated the upgrading of recycled lube oil by hydrogenation using commercial, synthetically-modified commercial catalysts, and synthesized catalysts. A down-flow (trickle bed) catalytic unit was used for the hydrogenation experiments. In addition to carrying out elemental analyses of the various feed and product fractions, characterization was undertaken using H{sup 1} and C{sup 13} NMR. Initially commercial were evaluated. Second these commercial catalysts were promoted with precious metals using atomic layer deposition (ALD). Performance improvements were observed that declined with catalyst aging. An alternate approach was undertaken to deeply upgrade ULI product oils. Using a synthesized catalyst, much lower hydrogenation temperatures were required than commercial catalysts. Other performance improvements were also observed. The resulting lube oil fractions were of high purity even at low reaction severity. The products recovered from both the ALD and other processes were water-white (even those from the low temperature, low residence time (high space velocity), low conversion runs). These results indicate that highly upgraded recycle lube oils can be produced using ALD-deposited active metal catalysts. The use of H{sup 1} and C{sup 13} NMR for the characterization of the treated lube oils has been shown to be effective

The risk stratification of adverse neonatal outcomes in women with gestational diabetes (STRONG) study

Aims: To assess the risk of adverse neonatal outcomes in women with gestational diabetes (GDM) by identifying subgroups of women at higher risk to recognize the characteristics most associated with an excess of risk. Methods: Observational, retrospective, multicenter study involving consecutive women with GDM. To identify distinct and homogeneous subgroups of women at a higher risk, the RECursive Partitioning and AMalgamation (RECPAM) method was used. Overall, 2736 pregnancies complicated by GDM were analyzed. The main outcome measure was the occurrence of adverse neonatal outcomes in pregnancies complicated by GDM. Results: Among study participants (median age 36.8 years, pre-gestational BMI 24.8 kg/m2), six miscarriages, one neonatal death, but no maternal death was recorded. The occurrence of the cumulative adverse outcome (OR 2.48, 95% CI 1.59–3.87), large for gestational age (OR 3.99, 95% CI 2.40–6.63), fetal malformation (OR 2.66, 95% CI 1.00–7.18), and respiratory distress (OR 4.33, 95% CI 1.33–14.12) was associated with previous macrosomia. Large for gestational age was also associated with obesity (OR 1.46, 95% CI 1.00–2.15). Small for gestational age was associated with first trimester glucose levels (OR 1.96, 95% CI 1.04–3.69). Neonatal hypoglycemia was associated with overweight (OR 1.52, 95% CI 1.02–2.27) and obesity (OR 1.62, 95% CI 1.04–2.51). The RECPAM analysis identified high-risk subgroups mainly characterized by high pre-pregnancy BMI (OR 1.68, 95% CI 1.21–2.33 for obese; OR 1.38 95% CI 1.03–1.87 for overweight). Conclusions: A deep investigation on the factors associated with adverse neonatal outcomes requires a risk stratification. In particular, great attention must be paid to the prevention and treatment of obesity