Micro and nano-patterning of single-crystal diamond by swift heavy ion irradiation

This paper presents experimental data and analysis of the structural damage caused by swift-heavy ion irradiation of single-crystal diamond. The patterned buried structural damage is shown to generate, via swelling, a mirror- pattern on the sample surface, which remains largely damage-free. While extensive results are available for light ion implantations, this effect is reported here for the first time in the heavy ion regime,where a completely different range of input parameters (in terms of ion species, energy, stopping power, etc.) is available for customized irradiation. The chosen ion species are Au and Br, in the energy range 10–40 MeV. The observed patterns, as characterized by profilometry and atomic force microscopy, are reported in a series ofmodel experiments,which show swelling patterns ranging from a few nm to above 200 nm. Moreover, a systematic phenomenological modeling is presented, inwhich surface swelling measurements are correlated to buried crystal damage. A comparison ismade with data for light ion implantations, showing good compatibilitywith the proposedmodels. The modeling presented in thiswork can be useful for the design and realization of micropatterned surfaces in single crystal diamond, allowing generating highly customized structures by combining appropriately chosen irradiation parameters and masks

Characteristics of patients operated for primary hyperparathyroidism at university hospitals in Türkiye: Differences among Türkiye's geographical regions

Purpose: The aim of this study was to define the clinical and laboratory characteristics of patients operated on for primary hyperpatathyroidism (PHPT) at university hospitals in Türkiye, and to investigate the differences in the clinical presentations of the disease between different geographical regions. Methods: Patients operated on for PHPT in the university hospitals of Türkiye were included in the study. The demographic, clinical, and laboratory findings and the operational data of the patients were investigated according to the whole country and to different geographical regions. Comparisons were performed according to whole country and regions. Results: A total of 1,162 cases were included in the study from different regions and 20 university hospitals. The mean age of patients was 52.4 ± 0.38 (mean ± standard error) in the general population of Türkiye. The rates of hypertension, urolithiasis, bone disease and 25-hydroxyvitamin D insufficiency were 35%, 18.6%, 67.6%, and 63%, respectively. The median parathormone (PTH), serum total calcium (Ca+2) and phosphorus value were 220 pg/mL (range, 70-2,500 pg/mL), 11.2 mg/dL (range, 9.5-11.2 mg/dL), and 2.4 mg/dL (range, 1-4.7 mg/dL), respectively. The median size of the adenomas resected was 16 mm (range, 4-70 mm). Significant differences were observed in the clinical and laboratory findings of the patients operated on due to PHPT between different geographical regions of Türkiye (P < 0.05). Conclusion: The clinical and laboratory characteristics of the patients with PHPT in different geographical regions of Türkiye differ. Furthermore, the general findings of the cases in Türkiye give us a hint that the severity of the disease here is somewhere between Eastern and Western countries. Copyright © 2016, the Korean Surgical Society

Next-generation sequencing reveals deep intronic cryptic ABCC8 and HADH splicing founder mutations causing hyperinsulinism by pseudoexon activation

Copyright © 2013 The American Society of Human Genetics. Published by Elsevier Inc.Next-generation sequencing (NGS) enables analysis of the human genome on a scale previously unachievable by Sanger sequencing. Exome sequencing of the coding regions and conserved splice sites has been very successful in the identification of disease-causing mutations, and targeting of these regions has extended clinical diagnostic testing from analysis of fewer than ten genes per phenotype to more than 100. Noncoding mutations have been less extensively studied despite evidence from mRNA analysis for the existence of deep intronic mutations in >20 genes. We investigated individuals with hyperinsulinaemic hypoglycaemia and biochemical or genetic evidence to suggest noncoding mutations by using NGS to analyze the entire genomic regions of ABCC8 (117 kb) and HADH (94 kb) from overlapping ~10 kb PCR amplicons. Two deep intronic mutations, c.1333-1013A>G in ABCC8 and c.636+471G>T HADH, were identified. Both are predicted to create a cryptic splice donor site and an out-of-frame pseudoexon. Sequence analysis of mRNA from affected individuals' fibroblasts or lymphoblastoid cells confirmed mutant transcripts with pseudoexon inclusion and premature termination codons. Testing of additional individuals showed that these are founder mutations in the Irish and Turkish populations, accounting for 14% of focal hyperinsulinism cases and 32% of subjects with HADH mutations in our cohort. The identification of deep intronic mutations has previously focused on the detection of aberrant mRNA transcripts in a subset of disorders for which RNA is readily obtained from the target tissue or ectopically expressed at sufficient levels. Our approach of using NGS to analyze the entire genomic DNA sequence is applicable to any disease

Co-circulation of West Nile virus and distinct insect-specific flaviviruses in Turkey

Background: Active vector surveillance provides an efficient tool for monitoring the presence or spread of emerging or re-emerging vector-borne viruses. This study was undertaken to investigate the circulation of flaviviruses. Mosquitoes were collected from 58 locations in 10 provinces across the Aegean, Thrace and Mediterranean Anatolian regions of Turkey in 2014 and 2015. Following morphological identification, mosquitoes were pooled and screened by nested and real-time PCR assays. Detected viruses were further characterised by sequencing. Positive pools were inoculated onto cell lines for virus isolation. Next generation sequencing was employed for genomic characterisation of the isolates. Results: A total of 12,711 mosquito specimens representing 15 species were screened in 594 pools. Eleven pools (2%) were reactive in the virus screening assays. Sequencing revealed West Nile virus (WNV) in one Culex pipiens (s.l.) pool from Thrace. WNV sequence corresponded to lineage one clade 1a but clustered distinctly from the Turkish prototype isolate. In 10 pools, insect-specific flaviviruses were characterised as Culex theileri flavivirus in 5 pools of Culex theileri and one pool of Cx. pipiens (s.l.), Ochlerotatus caspius flavivirus in two pools of Aedes (Ochlerotatus) caspius, Flavivirus AV-2011 in one pool of Culiseta annulata, and an undetermined flavivirus in one pool of Uranotaenia unguiculata from the Aegean and Thrace regions. DNA forms or integration of the detected insect-specific flaviviruses were not observed. A virus strain, tentatively named as “Ochlerotatus caspius flavivirus Turkey”, was isolated from an Ae. caspius pool in C6/36 cells. The viral genome comprised 10,370 nucleotides with a putative polyprotein of 3,385 amino acids that follows the canonical flavivirus polyprotein organisation. Sequence comparisons and phylogenetic analyses revealed the close relationship of this strain with Ochlerotatus caspius flavivirus from Portugal and Hanko virus from Finland. Several conserved structural and amino acid motifs were identified. Conclusions: We identified WNV and several distinct insect-specific flaviviruses during an extensive biosurveillance study of mosquitoes in various regions of Turkey in 2014 and 2015. Ongoing circulation of WNV is revealed, with an unprecedented genetic diversity. A probable replicating form of an insect flavivirus identified only in DNA form was detected

Micro and nano-patterning of single-crystal diamond by swift heavy ion irradiation

© 2016 Elsevier B.V.This paper presents experimental data and analysis of the structural damage caused by swift-heavy ion irradiation of single-crystal diamond. The patterned buried structural damage is shown to generate, via swelling, a mirror-pattern on the sample surface, which remains largely damage-free. While extensive results are available for light ion implantations, this effect is reported here for the first time in the heavy ion regime, where a completely different range of input parameters (in terms of ion species, energy, stopping power, etc.) is available for customized irradiation. The chosen ion species are Au and Br, in the energy range 10–40 MeV. The observed patterns, as characterized by profilometry and atomic force microscopy, are reported in a series of model experiments, which show swelling patterns ranging from a few nm to above 200 nm. Moreover, a systematic phenomenological modeling is presented, in which surface swelling measurements are correlated to buried crystal damage. A comparison is made with data for light ion implantations, showing good compatibility with the proposed models. The modeling presented in this work can be useful for the design and realization of micropatterned surfaces in single crystal diamond, allowing generating highly customized structures by combining appropriately chosen irradiation parameters and masks.GG acknowledges support from the ALBA synchrotron, W. Schildkamp for inspiring discussions on the behaviour of diamond and J. Ferrer for his help in experiment preparation. GG, MD-H, VT-M, OP-R and JO acknowledge the projects MAT-2011-28379-C03-02 of the Spanish Ministry of Economy and Competitiveness, TECHNOFUSION(II)CM (S2013/MAE2745) of the Community of Madrid, and Moncloa Campus of International Excellence (UCM-UPM) foundation for offering a PICATA postdoctoral fellowship (OP-R). FP is supported by the “DiNaMo” project no. 157660 funded by National Institute of Nuclear Physics. PO is supported by the FIRB “Futuro in Ricerca 2010” project (CUP code: D11J11000450001) funded by MIUR and by the “A.Di.N-Tech.” project (CUP code: D15E13000130003) funded by the University of Torino and “Compagnia di San Paolo”. The MeV ion beam implantations performed at the INFN Legnaro National Laboratories was supported by the “Dia.Fab.” experiment, and those at the INFN LABEC Laboratory by the “FARE” and “CICAS” experiments. NMP is supported by the European Research Council (ERC StG Ideas 2011 BIHSNAM no. 279985, ERC PoC 2013-2 KNOTOUGH no. 632277 and ERC PoC 2015 SILKENE no. 693670), by the European Commission under the Graphene Flagship (“Nanocomposites”, no. 604391). FB acknowledges support from BIHSNAM. LL-M and CO acknowledge the Spanish MINECO through the Severo Ochoa Program (SEV-2015-0496) and MAT2013-47869-C4-1-P. CO acknowledges the specific agreement between ICMAB-CSIC and the Synchrotron Light Facility ALBA

A HIF1α Regulatory Loop Links Hypoxia and Mitochondrial Signals in Pheochromocytomas

Pheochromocytomas are neural crest–derived tumors that arise from inherited or sporadic mutations in at least six independent genes. The proteins encoded by these multiple genes regulate distinct functions. We show here a functional link between tumors with VHL mutations and those with disruption of the genes encoding for succinate dehydrogenase (SDH) subunits B (SDHB) and D (SDHD). A transcription profile of reduced oxidoreductase is detected in all three of these tumor types, together with an angiogenesis/hypoxia profile typical of VHL dysfunction. The oxidoreductase defect, not previously detected in VHL-null tumors, is explained by suppression of the SDHB protein, a component of mitochondrial complex II. The decrease in SDHB is also noted in tumors with SDHD mutations. Gain-of-function and loss-of-function analyses show that the link between hypoxia signals (via VHL) and mitochondrial signals (via SDH) is mediated by HIF1α. These findings explain the shared features of pheochromocytomas with VHL and SDH mutations and suggest an additional mechanism for increased HIF1α activity in tumors

Elevated gamma glutamyl transferase levels are associated with the location of acute pulmonary embolism. Cross-sectional evaluation in hospital setting

ABSTRACT CONTEXT AND OBJECTIVE: The location of embolism is associated with clinical findings and disease severity in cases of acute pulmonary embolism. The level of gamma-glutamyl transferase increases under oxidative stress-related conditions. In this study, we investigated whether gamma-glutamyl transferase levels could predict the location of pulmonary embolism. DESIGN AND SETTING: Hospital-based cross-sectional study at Cumhuriyet University, Sivas, Turkey. METHODS : 120 patients who were diagnosed with acute pulmonary embolism through computed tomography-assisted pulmonary angiography were evaluated. They were divided into two main groups (proximally and distally located), and subsequently into subgroups according to thrombus localization as follows: first group (thrombus in main pulmonary artery; n = 9); second group (thrombus in main pulmonary artery branches; n = 71); third group (thrombus in pulmonary artery segmental branches; n = 34); and fourth group (thrombus in pulmonary artery subsegmental branches; n = 8). RESULTS : Gamma-glutamyl transferase levels on admission, heart rate, oxygen saturation, right ventricular dilatation/hypokinesia, pulmonary artery systolic pressure and cardiopulmonary resuscitation requirement showed prognostic significance in univariate analysis. The multivariate logistic regression model showed that gamma-glutamyl transferase level on admission (odds ratio, OR = 1.044; 95% confidence interval, CI: 1.011-1.079; P = 0.009) and pulmonary artery systolic pressure (OR = 1.063; 95% CI: 1.005-1.124; P = 0.033) remained independently associated with proximally localized thrombus in pulmonary artery. CONCLUSIONS : The findings revealed a significant association between increased existing embolism load in the pulmonary artery and increased serum gamma-glutamyl transferase levels

Contributions of patient and citizen researchers to 'Am I the right way up?' study of balance in posterior cortical atrophy and typical Alzheimer's disease

The current report describes the journey from the sharing of a single, extraordinary experience during a support group conversation to the development of a novel scientific investigation of balance problems in a rarer form of dementia. The story centres around the involvement of people living with or caring for someone with posterior cortical atrophy (often referred to as the visual variant of Alzheimer’s disease) in highlighting hitherto under-appreciated consequences of their condition upon their ability to know ‘Am I the right way up?’. We describe how comments and descriptions of these balance symptoms were collated and communicated, and the involvement of people with posterior cortical atrophy in shaping a series of scientific hypotheses and developing and adapting appropriate experimental materials and procedures. We also reflect more broadly on how we might better recognise, acknowledge and encourage different forms of involvement, and describe several engagement-inspired extensions to the research involving people living with dementia, scientists and artists