Scaling Behaviour of Si-alloyed Steel Slabs under Reheating Conditions

Reheating of steel slabs for further processing such as hot rolling usually takes place in gas-fired pusher furnaces. Temperatures well above 1000°C, combined with an atmosphere containing H2O, CO2, and O2, lead to substantial oxidation of most steel grades. Newly developed advanced steels often contain significant amounts of Si. This element plays a dominant role in the scaling behaviour near the steel-scale-interface, since fayalite (Fe2SiO4) forms a eutectic with wuestite (Fe1–xO) that melts as low as 1177°C.To better understand the high temperature oxidation behaviour, lab-scale trials were performed with different steel grades containing up to 3 wt.% Si. Possible interactions of Si with other alloying elements present in the samples such as Cr, Mn and Al were also of interest. The atmosphere contained 20% H2O, 7% CO2, and 3% O2, resembling reheating conditions in pusher furnaces, and temperatures ranged from 1100 to 1240°C. For metallographic investigation, the oxidised samples were cold mounted under vacuum using taper section angles. After preparation, the sections were examined through light microscopy, SEM/EDS, XRD, and TEM. The local distribution of the alloying elements could be mapped efficiently, and phase identification was successful in most parts. Under the applied experimental conditions, the elements of interest were present in their oxidic form either as pure or as mixed oxides. Higher Si-contents led to an increased build-up of eutectic melting phase at the steel-scale-interface at temperatures above 1177°C, which in turn further accelerated the oxidation

Virtuelles Pubquiz: (k)ein Kahoot! mit Mehrwert

In diesem Beitrag wird vor dem Hintergrund der aktuellen Situation der Fernlehre an Hochschulen das virtuelle Pubquiz als methodisch-didaktisches Format vorgestellt, das sich von traditionellen Quiz-Formaten vom Typ Kahoot! durch Konzeption und Design unterscheidet.Against the background of the current situation of distance learning at universities, this article presents the virtual pub quiz as a methodological-didactic format that differs from traditional quiz formats of the Kahoot! type in conception and design

Open questions in the social lives of viruses

Social interactions among viruses occur whenever multiple viral genomes infect the same cells, hosts, or populations of hosts. Viral social interactions range from cooperation to conflict, occur throughout the viral world, and affect every stage of the viral lifecycle. The ubiquity of these social interactions means that they can determine the population dynamics, evolutionary trajectory, and clinical progression of viral infections. At the same time, social interactions in viruses raise new questions for evolutionary theory, providing opportunities to test and extend existing frameworks within social evolution. Many opportunities exist at this interface: Insights into the evolution of viral social interactions have immediate implications for our understanding of the fundamental biology and clinical manifestation of viral diseases. However, these opportunities are currently limited because evolutionary biologists only rarely study social evolution in viruses. Here, we bridge this gap by (1) summarizing the ways in which viruses can interact socially, including consequences for social evolution and evolvability; (2) outlining some open questions raised by viruses that could challenge concepts within social evolution theory; and (3) providing some illustrative examples, data sources, and conceptual questions, for studying the natural history of social viruses

Fast-forwarding evolution—Accelerated adaptation in a proofreading-deficient hypermutator herpesvirus

Evolution relies on the availability of genetic diversity for fitness-based selection. However, most deoxyribonucleic acid (DNA) viruses employ DNA polymerases (Pol) capable of exonucleolytic proofreading to limit mutation rates during DNA replication. The relative genetic stability produced by high-fidelity genome replication can make studying DNA virus adaptation and evolution an intensive endeavor, especially in slowly replicating viruses. Here, we present a proofreading-impaired Pol mutant (Y547S) of Marek’s disease virus that exhibits a hypermutator phenotype while maintaining unimpaired growth in vitro and wild-type (WT)-like pathogenicity in vivo. At the same time, mutation frequencies observed in Y547S virus populations are 2–5-fold higher compared to the parental WT virus. We find that Y547S adapts faster to growth in originally non-permissive cells, evades pressure conferred by antiviral inhibitors more efficiently, and is more easily attenuated by serial passage in cultured cells compared to WT. Our results suggest that hypermutator viruses can serve as a tool to accelerate evolutionary processes and help identify key genetic changes required for adaptation to novel host cells and resistance to antiviral therapy. Similarly, the rapid attenuation achieved through adaptation of hypermutators to growth in cell culture enables identification of genetic changes underlying attenuation and virulence, knowledge that could practically exploited, e.g. in the rational design of vaccines

Liver Fibrosis-4 index indicates atrial fibrillation in acute ischemic stroke

BACKGROUND: Non-alcoholic fatty liver disease and particularly liver fibrosis is related to cardiovascular disease and may indicate an increased risk for atrial fibrillation (AF), but this association has not yet been systematically investigated in a cohort of ischemic stroke patients. METHODS: We analyzed data from a prospective single-center study enrolling all consecutive ischemic stroke patients admitted to our stroke unit over a one-year-period. All patients received a thorough etiological work-up. For evaluation of liver fibrosis, we determined the FIB-4 index, a well-established noninvasive liver fibrosis test. Laboratory results were analyzed from a uniform blood sample taken at stroke unit admission. RESULTS: Of 414 included patients (mean age 70.2 years, 57.7% male), FIB-4 indicated advanced liver fibrosis in 92 (22.2%). AF as the underlying stroke mechanism was present in 28.0% (large vessel disease: 25.6%, small vessel disease: 11.4%, cryptogenic: 29.2%). Patients with FIB-4 ≥2.67 had higher rates of AF (53.3% vs. 20.8%, p<0.001), this association remained significant after correction for established AF risk factors (Odds Ratio 2.53, 95% confidence interval 1.44-4.46, p=0.001). FIB-4 was further associated with worse functional outcome three months (p<0.001) and higher mortality four years post-stroke (p<0.02), but these relationships were no longer present after correction for age and initial stroke severity. Moreover, FIB-4 did not associate with long-term recurrent vascular events. CONCLUSIONS: Liver fibrosis assessed by the FIB-4 index is independently associated with AF in acute ischemic stroke patients. Further studies should evaluate whether adding the FIB-4 index to AF risk scores increases their precision

Association of Presence and Pattern of MRI Markers of Cerebral Small Vessel Disease With Recurrent Intracerebral Hemorrhage.

BACKGROUND Assessing the risk of recurrent intracerebral hemorrhage (ICH) is of high clinical importance. MRI-based cerebral small vessel disease (SVD) markers may help establish ICH etiological subtypes (including cryptogenic ICH) relevant for recurrence risk. METHODS We investigated the risk of recurrent ICH in a large cohort of consecutive ICH survivors with available MRI at baseline. Patients with macrovascular, structural or other identified secondary causes (other than SVD) were excluded. Based on MRI findings, ICH etiology was defined as probable cerebral amyloid angiopathy (CAA) according to the Boston 2.0 criteria, arteriolosclerosis (non-lobar ICH and additional markers of arteriolosclerosis, absent lobar hemorrhagic lesions), mixed SVD (mixed deep and lobar hemorrhagic changes) or cryptogenic (no MRI markers of SVD). Recurrent ICH was determined using electronic health records and confirmed by neuroimaging. Data from an independent multi-center cohort (CROMIS-2 ICH) was used to confirm core findings. RESULTS Of 443 patients with ICH (mean age 67±13 years, 41% female), ICH etiology was mixed SVD in 36.7%, arteriolosclerosis in 23.6%, CAA in 23.0%, and cryptogenic in 16.7%. During a median follow-up period of 5.7 years (IQR 2.9-10.0, 2682 patient-years), recurrent ICH were found in 59 individual patients (13.3%). The highest recurrence rate per 100 person-years was detected in patients with CAA (8.5, 95% CI 6.1-11.7), followed by mixed SVD (1.8, 95% CI 1.1-2.9) and arteriolosclerosis (0.6, 95% CI 0.3-1.5). No recurrent ICH occurred in patients with cryptogenic ICH during 510 person-years follow-up (97.5% CI, 0-0.7); this finding was confirmed in an independent cohort (CROMIS-2 ICH, n=216), in which there was also no recurrence in patients with cryptogenic ICH. In patients with CAA, cortical superficial siderosis was the imaging feature strongest related with ICH recurrence (hazard ratio 5.7, 95% CI 2.4-13.6). CONCLUSIONS MRI-based etiological subtypes are helpful in determining the recurrence risk of ICH; while the highest recurrence risk was found in CAA, recurrence risk was low for arteriolosclerosis, and negligible for cryptogenic ICH

Association of Presence and Pattern of MRI Markers of Cerebral Small Vessel Disease With Recurrent Intracerebral Hemorrhage

BACKGROUND: Assessing the risk of recurrent intracerebral hemorrhage (ICH) is of high clinical importance. MRI-based cerebral small vessel disease (SVD) markers may help establish ICH etiological subtypes (including cryptogenic ICH) relevant for recurrence risk. METHODS: We investigated the risk of recurrent ICH in a large cohort of consecutive ICH survivors with available MRI at baseline. Patients with macrovascular, structural or other identified secondary causes (other than SVD) were excluded. Based on MRI findings, ICH etiology was defined as probable cerebral amyloid angiopathy (CAA) according to the Boston 2.0 criteria, arteriolosclerosis (non-lobar ICH and additional markers of arteriolosclerosis, absent lobar hemorrhagic lesions), mixed SVD (mixed deep and lobar hemorrhagic changes) or cryptogenic (no MRI markers of SVD). Recurrent ICH was determined using electronic health records and confirmed by neuroimaging. Data from an independent multi-center cohort (CROMIS-2 ICH) was used to confirm core findings. RESULTS: Of 443 patients with ICH (mean age 67±13 years, 41% female), ICH etiology was mixed SVD in 36.7%, arteriolosclerosis in 23.6%, CAA in 23.0%, and cryptogenic in 16.7%. During a median follow-up period of 5.7 years (IQR 2.9-10.0, 2682 patient-years), recurrent ICH were found in 59 individual patients (13.3%). The highest recurrence rate per 100 person-years was detected in patients with CAA (8.5, 95% CI 6.1-11.7), followed by mixed SVD (1.8, 95% CI 1.1-2.9) and arteriolosclerosis (0.6, 95% CI 0.3-1.5). No recurrent ICH occurred in patients with cryptogenic ICH during 510 person-years follow-up (97.5% CI, 0-0.7); this finding was confirmed in an independent cohort (CROMIS-2 ICH, n=216), in which there was also no recurrence in patients with cryptogenic ICH. In patients with CAA, cortical superficial siderosis was the imaging feature strongest related with ICH recurrence (hazard ratio 5.7, 95% CI 2.4-13.6). CONCLUSIONS: MRI-based etiological subtypes are helpful in determining the recurrence risk of ICH; while the highest recurrence risk was found in CAA, recurrence risk was low for arteriolosclerosis, and negligible for cryptogenic ICH

Midbrain–hindbrain malformations in patients with malformations of cortical development and epilepsy: A series of 220 patients

SummaryMidbrain–hindbrain malformations (MHM) may coexist with malformations of cortical development (MCD). This study represents a first attempt to investigate the spectrum of MHM in a large series of patients with MCD and epilepsy. We aimed to explore specific associations between MCD and MHM and to compare two groups of patients: MCD with MHM (wMHM) and MCD without MHM (w/oMHM) with regard to clinical and imaging features.Two hundred and twenty patients (116 women/104 men, median age 28 years, interquartile range 20–44 years at the time of assessment) with MCD and epilepsy were identified at the Departments of Neurology and Pediatrics, Innsbruck Medical University, Austria. All underwent high-resolution MRIs (1.5-T) between 01.01.2002 and 31.12.2011. Midbrain–hindbrain structures were visually assessed by three independent raters.MHM were seen in 17% (38/220) of patients. The rate of patients wMHM and w/oMHM differed significantly (p=0.004) in three categories of MCD (category I – to abnormal neuronal proliferation; category II – to abnormal neuronal migration; and category III – due to abnormal neuronal late migration/organization): MCD due to abnormal neuronal migration (31%) and organization (23%) were more commonly associated with MHM compared to those with MCD due to abnormal neuronal proliferation (9%). Extensive bilateral MCD were seen more often in patients wMHM compared to those w/oMHM (63% vs. 36%; p=0.004). In wMHM group compared to w/oMHM group there were higher rates of callosal dysgenesis (26% vs. 4%; p<0.001) and hippocampal abnormalities (52% vs. 27%; p<0.001). Patients wMHM were younger (median 25 years vs. 30 years; p=0.010) at the time of assessment and had seizure onset at an earlier age (median 5 years vs. 12 years; p=0.043) compared to those w/oMHM. Patients wMHM had higher rates of learning disability (71% vs. 38%; p<0.001), delayed developmental milestones (68% vs. 35%; p<0.001) and neurological deficits (66% vs. 47%; p=0.049) compared to those w/oMHM.The groups (wMHM and w/oMHM) did not differ in their response to antiepileptic treatment, seizure outcome, seizure types, EEG abnormalities and rate of status epilepticus. Presence of MHM in patients with MCD and epilepsy is associated with severe morphological and clinical phenotypes

Gene rearrangement and Chernobyl related thyroid cancers

The increase in thyroid carcinoma post-Chernobyl has been largely confined to a specific subtype of papillary carcinoma (solid/follicular). This subtype is observed predominantly in children under 10 in unirradiated populations, but maintains a high frequency in those aged 10–15 from those areas exposed to fallout from the Chernobyl accident. The aim of this study was to link morphology with molecular biology. We examined 106 papillary carcinomas from children under the age of 15 at operation. All were examined for rearrangements of the RET oncogene by reverse transcription polymerase chain reaction (RT-PCR); a subset of these cases were also examined for mutations of the three ras oncogenes, exon 10 of the thyroid stimulating hormone receptor, associated more usually with a follicular rather than papillary morphology, and exons 5, 6, 7 and 8 of the p53 gene, commonly involved in undifferentiated thyroid carcinoma. Rearrangements of the RET oncogene were found in 44% of papillary carcinomas in which we studied fresh material; none of the tumours examined showed mutation in any of the other genes. The two rearrangements resulting from inversion of part of chromosome 10 (PTC1 and PTC3) accounted for the majority of RET rearrangements identified, with PTC1 being associated with papillary carcinomas of the classic and diffuse sclerosing variants and PTC3 with the solid/follicular variant. © 2000 Cancer Research Campaig

Biomarker analysis of cetuximab plus oxaliplatin/leucovorin/5-fluorouracil in first-line metastatic gastric and oesophago-gastric junction cancer: results from a phase II trial of the Arbeitsgemeinschaft Internistische Onkologie (AIO)

<p>Abstract</p> <p>Background</p> <p>The activity of the epidermal growth factor receptor (EGFR)-directed monoclonal antibody cetuximab combined with oxaliplatin/leucovorin/5-fluorouracil (FUFOX) was assessed in first-line metastatic gastric and oesophago-gastric junction (OGJ) cancer in a prospective phase II study showing a promising objective tumour response rate of 65% and a low mutation frequency of <it>KRAS </it>(3%). The aim of the correlative tumour tissue studies was to investigate the relationship between <it>EGFR </it>gene copy numbers, activation of the EGFR pathway, expression and mutation of E-cadherin, V600E BRAF mutation and clinical outcome of patients with gastric and OGJ cancer treated with cetuximab combined with FUFOX.</p> <p>Methods</p> <p>Patients included in this correlative study (<it>n </it>= 39) were a subset of patients from the clinical phase II study. The association between <it>EGFR </it>gene copy number, activation of the EGFR pathway, abundance and mutation of E-cadherin which plays an important role in these disorders, BRAF mutation and clinical outcome of patients was studied. <it>EGFR </it>gene copy number was assessed by FISH. Expression of the phosphorylated forms of EGFR and its downstream effectors Akt and MAPK, in addition to E-cadherin was analysed by immunohistochemistry. The frequency of mutant V600E BRAF was evaluated by allele-specific PCR and the mutation profile of the E-cadherin gene <it>CDH1 </it>was examined by DHPLC followed by direct sequence analysis. Correlations with overall survival (OS), time to progression (TTP) and overall response rate (ORR) were assessed.</p> <p>Results</p> <p>Our study showed a significant association between increased <it>EGFR </it>gene copy number (≥ 4.0) and OS in gastric and OGJ cancer, indicating the possibility that patients may be selected for treatment on a genetic basis. Furthermore, a significant correlation was shown between activated EGFR and shorter TTP and ORR, but not between activated EGFR and OS. No V600E BRAF mutations were identified. On the other hand, an interesting trend between high E-cadherin expression levels and better OS was observed and two <it>CDH1 </it>exon 9 missense mutations (A408V and D402H) were detected.</p> <p>Conclusion</p> <p>Our finding that increased <it>EGFR </it>gene copy numbers, activated EGFR and the E-cadherin status are potentially interesting biomarkers needs to be confirmed in larger randomized clinical trials.</p> <p>Trial registration</p> <p>Multicentre clinical study with the European Clinical Trials Database number 2004-004024-12.</p