Microstructure Characterization in Individual Texture Components by X-Ray Line Profile Analysis: Principles of the X-TEX Method and Practical Application to Tensile-Deformed Textured Ti

A novel X-ray diffraction-based method and computer program X-TEX has been developed to determine the microstructure in individual texture components of polycrystalline, textured materials. Two different approaches are presented. In the first one, based on the texture of the specimen, the X-TEX software provides optimized specimen orientations for X-ray diffraction experiments in which diffraction peaks consist of intensity contributions stemming from grain populations of separate texture components in the specimen. Texture-specific diffraction patterns can be created by putting such peaks together from different measurements into an artificial pattern for each texture component. In the second one, the X-TEX software can determine the intensity contributions of different texture components to diffraction peaks measured in a particular sample orientation. According to this, peaks belonging mainly to one of the present texture components are identified and grouped into the same quasi-phase during the evaluation procedure. The X-TEX method was applied and tested on tensile-deformed, textured, commercially pure titanium samples. The patterns were evaluated by the convolutional multiple whole profile (CMWP) procedure of line profile analysis for dislocation densities, dipole character, slip systems and subgrain size for three different texture components of the Ti specimens. Significant differences were found in the microstructure evolution in the two major and the random texture components. The dislocation densities were discussed by the Taylor model of work hardening

Geenivarojen suojelu

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Suomen kansallisten kasvigeenivarojen pitkäaikaissäilytysohjeet : Vihannes-, yrtti- ja rohdoskasvit

Suomen kansallinen kasvigeenivaraohjelma perustettiin vuonna 2003 tehostamaan maa- ja metsätalouden geenivarojen suojelua maassamme. MTT:n vastuulla on ohjelman koordinointi sekä maatalous- ja puutarhakasvien suojelu. Metsäntutkimuslaitos vastaa puolestaan metsäpuiden geenivarojen suojelusta. Perustuslain mukaan vastuu luonnosta ja sen monimuotoisuudesta sekä ympäristöstä ja kulttuuriperinnöstä kuuluu kaikille. Niinpä myös kansalaisilla ja erilaisilla yhdistyksillä on ohjelman toteuttamisessa tärkeä rooli. Vihannesten, yrttien ja rohdoskasvien pitkäaikaissäilytyksen ohjeet palvelevat geenivarojen säilytyksen käytännön toteutusta. Ne on laadittu suomalaisissa kasvigeenivarakokoelmissa jo oleville lajeille ja uhanalaiselle lajistolle, joka voisi olla tärkeää tulevaisuudessa. Nyt mukana olevat kasvit ovat sipulit (Allium spp.), Brassica-suvun lajit nauris, lanttu ja kaali, merikaali (Crambe martima), raparperi (Rheum), piparjuuri (Amoracia rusticana), mintut (Mentha ssp.), etelänarnikki (Arnica montana), kalmojuuri (Acorus calamus) ja humala (Humulus lupulus). Ohjeissa on kartoitettu MTT:n nykyiset kokoelmat ja esitetty tarvittavat toimet geenivarojen säilyttämiseksi. Ne palvelevat myös käsikirjana muun muassa kenttäkokoelmia perustettaessa ja uudistettaessa sekä muita, vaihtoehtoisia säilytystapoja valittaessa. Ohjeista on mahdollisesti hyötyä myös harrastajille. Ohjeistukseen kuuluvia lajeja säilytetään pääasiallisesti siemeninä ja kasvullisissa kokoelmissa. Tulevaisuudessa panostetaan mahdollisuuksien mukaan lisääntyvästi in vitro- ja kylmäsäilytykseen.The Finnish National Programme for Plant Genetic Resources was established in 2003 to facilitate the conservation of agricultural and forest genetic resources in Finland. MTT Agrifood Research Finland is responsible for the coordination of the programme and for the preservation of field and horticultural crop genetic resources. According to the Finnish constitution, all citizens and organizations are responsible for nature, its diversity, the environment and Finnish cultural heritage, and thus all contribute to the realization of the programme. The guidelines for the long-term conservation of vegetables, herbs and medicinal plants describe the practical implementation of the gene resource preservation. Guidelines are given for those species/genera that are found in the present Finnish collections or those that have pontential in the future. The species/genera included are onions (Allium ssp), Brassicas turnip, swede, cababges and seakale, rhubarb (Rheum L.), horse radish (Amoracia rusticana), mints (Mentha ssp.), mountain-tobacco (Arnica montana L), swet-flag (Acorus calamus L.) and hop (Humulus lupulus L.). The guidelines describe the present scope of MTT s collections of vegetables, herbs and medicinal plants. The criteria for selecting material to be preserved are also presented. Instructions are included for the establishment and renewal of collections and for selecting alternative preservation methods. At present collections are preserved mainly as seeds and in field gene banks; species-specific cryopreservation applications are still under development and the equipment required for the preservation has only recently been acquired. For the future, plans call for the most valuable material to be cryopreserved, because open-air field gene banks are subject to disease, pests and variable weather conditions. In some cases, maintaining plant material under slow growth conditions in vitro is appropriate.vokMyynti MTT Tietopalvelut 31600 JokioinenGuidelines for long-term conservation of Finnish plant genetic resources Vegetables, herbs and medicinal plant

Resolving the phylogenetic origin of glioblastoma via multifocal genomic analysis of pre-treatment and treatment-resistant autopsy specimens

Glioblastomas are malignant neoplasms composed of diverse cell populations. This intratumoral diversity has an underlying architecture, with a hierarchical relationship through clonal evolution from a common ancestor. Therapies are limited by emergence of resistant subclones from this phylogenetic reservoir. To characterize this clonal ancestral origin of recurrent tumors, we determined phylogenetic relationships using whole exome sequencing of pre-treatment IDH1/2 wild-type glioblastoma specimens, matched to post-treatment autopsy samples (n = 9) and metastatic extracranial post-treatment autopsy samples (n = 3). We identified “truncal” genetic events common to the evolutionary ancestry of the initial specimen and later recurrences, thereby inferring the identity of the precursor cell population. Mutations were identified in a subset of cases in known glioblastoma genes such as NF1(n = 3), TP53(n = 4) and EGFR(n = 5). However, by phylogenetic analysis, there were no protein-coding mutations as recurrent truncal events across the majority of cases. In contrast, whole copy-loss of chromosome 10 (12 of 12 cases), copy-loss of chromosome 9p21 (11 of 12 cases) and copy-gain in chromosome 7 (10 of 12 cases) were identified as shared events in the majority of cases. Strikingly, mutations in the TERT promoter were also identified as shared events in all evaluated pairs (9 of 9). Thus, we define four truncal non-coding genomic alterations that represent early genomic events in gliomagenesis, that identify the persistent cellular reservoir from which glioblastoma recurrences emerge. Therapies to target these key early genomic events are needed. These findings offer an evolutionary explanation for why precision therapies that target protein-coding mutations lack efficacy in GBM

A Clinical Rule for Preoperative Prediction of BRAF Mutation Status in Craniopharyngiomas

Papillary craniopharyngiomas are characterized by BRAFV600E mutations. Targeted therapy can elicit a dramatic radiographic regression of these tumors. Therefore, prediction of BRAF mutation status before definitive surgery could enable neoadjuvant treatment strategies. To establish preoperative prediction criteria to identify patients with a BRAF mutant craniopharyngioma. Sixty-four patients with craniopharyngioma were included in this study. We determined BRAF mutation status by targeted sequencing. After scoring interobserver variability between presurgical clinical data and radiographic features, we established a diagnostic rule for BRAF mutation in our discovery cohort. We then validated the rule in an independent cohort. The BRAFV600E mutation was detected in 12 of 42 patients in the discovery cohort. There were no patients under age 18 with BRAF mutation. Calcification was rare in tumors with BRAF mutation (P < .001), and 92% of them were supradiaphragmatic in location. Combining these 3 features-older than 18 years, absence of calcification, and supradiaphragmatic tumor location-we established a rule for predicting BRAF mutation. In cases where all 3 criteria were fulfilled, the sensitivity and specificity for the presence of BRAF mutation were 83% and 93%, respectively. In the validation cohort (n = 22), the sensitivity was 100% and specificity was 89%. We propose predictive criteria for a BRAF mutation in craniopharyngioma using preoperative clinical and radiographic data. This rule may be useful in identifying patients who could potentially benefit from neoadjuvant BRAFV600E-targeted systemic therapies

Genomic and transcriptomic correlates of immunotherapy response within the tumor microenvironment of leptomeningeal metastases

AbstractLeptomeningeal disease (LMD) is a devastating complication of solid tumor malignancies, with dire prognosis and no effective systemic treatment options. Over the past decade, the incidence of LMD has steadily increased due to therapeutics that have extended the survival of cancer patients, highlighting the need for new interventions. To examine the efficacy of immune checkpoint inhibitors (ICI) in patients with LMD, we completed two phase II clinical trials. Here, we investigate the cellular and molecular features underpinning observed patient trajectories in these trials by applying single-cell RNA and cell-free DNA profiling to longitudinal cerebrospinal fluid (CSF) draws from enrolled patients. We recover immune and malignant cell types in the CSF, characterize cell behavior changes following ICI, and identify genomic features associated with relevant clinical phenomena. Overall, our study describes the liquid LMD tumor microenvironment prior to and following ICI treatment and demonstrates clinical utility of cell-free and single-cell genomic measurements for LMD research.</jats:p

DMD genomic deletions characterize a subset of progressive/higher-grade meningiomas with poor outcome

Progressive meningiomas that have failed surgery and radiation have a poor prognosis and no standard therapy. While meningiomas are more common in females overall, progressive meningiomas are enriched in males. We performed a comprehensive molecular characterization of 169 meningiomas from 53 patients with progressive/high-grade tumors, including matched primary and recurrent samples. Exome sequencing in an initial cohort (n = 24) detected frequent alterations in genes residing on the X chromosome, with somatic intragenic deletions of the dystrophin-encoding and muscular dystrophy-associated DMD gene as the most common alteration (n = 5, 20.8%), along with alterations of other known X-linked cancer-related genes KDM6A (n = 2, 8.3%), DDX3X, RBM10 and STAG2 (n = 1, 4.1% each). DMD inactivation (by genomic deletion or loss of protein expression) was ultimately detected in 17/53 progressive meningioma patients (32%). Importantly, patients with tumors harboring DMD inactivation had a shorter overall survival (OS) than their wild-type counterparts [5.1years (95% CI 1.3-9.0) vs. median not reached (95% CI 2.9-not reached, p = 0.006)]. Given the known poor prognostic association of TERT alterations in these tumors, we also assessed for these events, and found seven patients with TERT promoter mutations and three with TERT rearrangements in this cohort (n = 10, 18.8%), including a recurrent novel RETREG1-TERT rearrangement that was present in two patients. In a multivariate model, DMD inactivation (p = 0.033, HR = 2.6, 95% CI 1.0-6.6) and TERT alterations (p = 0.005, HR = 3.8, 95% CI 1.5-9.9) were mutually independent in predicting unfavorable outcomes. Thus, DMD alterations identify a subset of progressive/high-grade meningiomas with worse outcomes