A graphene electron lens

International audienceAn epitaxial layer of graphene was grown on a pre patterned 6H-SiC(0001) crystal. The graphene smoothly covers the hexagonal nano-holes in the substrate without the introduction of small angle grain boundaries or dislocations. This is achieved by an elastic deformation of the graphene by ~0.3% in accordance to its large elastic strain limit. This elastic stretching of the graphene leads to a modification of the band structure and to a local lowering of the electron group velocity of the graphene. We propose to use this effect to focus two-dimensional electrons in analogy to simple optical lenses

Comprehensive Immune Monitoring of Clinical Trials to Advance Human Immunotherapy.

The success of immunotherapy has led to a myriad of clinical trials accompanied by efforts to gain mechanistic insight and identify predictive signatures for personalization. However, many immune monitoring technologies face investigator bias, missing unanticipated cellular responses in limited clinical material. We present here a mass cytometry (CyTOF) workflow for standardized, systems-level biomarker discovery in immunotherapy trials. To broadly enumerate immune cell identity and activity, we established and extensively assessed a reference panel of 33 antibodies to cover major cell subsets, simultaneously quantifying activation and immune checkpoint molecules in a single assay. This assay enumerates ≥98% of peripheral immune cells with ≥4 positively identifying antigens. Robustness and reproducibility are demonstrated on multiple samples types, across two research centers and by orthogonal measurements. Using automated analysis, we identify stratifying immune signatures in bone marrow transplantation-associated graft-versus-host disease. Together, this validated workflow ensures comprehensive immunophenotypic analysis and data comparability and will accelerate biomarker discovery

Relationship between oral health and demographic characteristics in retired elderly people in Iran بررس� ارتباط س�ا٠ت د�ا� با ٠شخصات ج٠ع� تش�اخت� سا�٠�دا� باز�شست�

Objectives The current study aimed to determine the relationship between oral health and demographic characteristics of retired elderly people. Methods & Materials This cross-sectional study was conducted on 158 older adults aged � 60 years. The subjects were selected using random sampling method and personnel codes. All the elderly participants were retired members of the Tehran Municipality Administration. The study data were collected by direct visit to the subjects' place of residence and conducting interviews. The data collection tool was a questionnaire that included 2 sections. The first section consisted of demographic, socioeconomic, and health profiles, while the second section consisted of Geriatric Oral Health Assessment Index (GOHAI). Results We collected data from 158 participants (90 men, 68 women). The mean age of the participants was 68.78 years. The obtained data suggested that 38 (24.05) participants had a poor state of oral health. About 50 of the participants mentioned high dental care costs as a reason for not referring to the dentist. According to the findings of this study, there is a direct relationship between educational level and oral health status in the elderly (P < 0.05). Conclusion Oral and dental health increase the quality of life in the elderly and reduce the high prevalence of dental problems among them. Therefore, designing and implementing practical policies to reduce oral and dental infections in the elderly and promote their health is necessary. © 2019. ا�دا� �د� از ا�� ٠طا�ع�� تع��� ارتباط س�ا٠ت د�ا� با ٠شخصات ج٠ع� تش�اخت� سا�٠�دا� باز�شست� ب�د. ٠�اد � ر�ش �ا ا�� پ���ش ب� ر�ش ت�ص�� �تح���� بر ر�� 158 ��ر سا�٠�د با�ا� 60 سا� تحت پ�شش ساز٠ا� باز�شستگ� ش�ردار� ت�را� ب� ر�ش �٠�� �گ�ر� تصاد�� ا�جا٠شد. داد ��ا ب� ص�رت ٠ست��٠� با ٠صاحب� ٠ست��٠گردآ�ر� شد. ابزار گردآ�ر� داد ��ا شا٠� پرس ش�ا٠� ٠شخصات ج٠ع� تش�اخت� � پرس ش�ا٠� شاخص س�جش س�ا٠ت د�ا� سا�٠�دا� ب�د. �ا�ت� �ا 90 ��ر ) 57 درصد( از پاسخگ��ا� سا�٠�دا� ٠رد � 68 ��ر ) 43 درصد( سا�٠�دا� ز� ب�د�د. ٠�ا�گ�� س� سا�٠�دا� ٠�رد ٠طا�ع� 78 / 68 سا� ب�د. س�ا٠ت د�ا� با س� ) 004 / P=0 (� ج�س ) 034 / P=0 (� � تحص��ات ) 0001 / P=0 ( رابط� ٠ع� �دار داشت. �ضع�ت س�ا٠ت د�ا� � د�دا� سا�٠�دا� ٠رد ب�تر از سا�٠�دا� ز� ب�د. �ت�ج� گ�ر� با ت�ج� ب� ا�٠�ت �را�ا� س�ا٠ت د�ا� � د�دا� در ا�زا�ش ک���ت ز�دگ� سا�٠�دا�� در ��گا٠طراح� ٠داخ�ات برا� ارت�ا� س�ا٠ت د�ا� سا�٠�دا�� ت�ج� ب� ���گ ��ا� ج٠ع� تش�اخت� آ ��ا ضر�ر� ب� �ظر ٠�رسد

Comprehensive Immune Monitoring of Clinical Trials to Advance Human Immunotherapy

The success of immunotherapy has led to a myriad of clinical trials accompanied by efforts to gain mechanistic insight and identify predictive signatures for personalization. However, many immune monitoring technologies face investigator bias, missing unanticipated cellular responses in limited clinical material. We present here a mass cytometry (CyTOF) workflow for standardized, systems-level biomarker discovery in immunotherapy trials. To broadly enumerate immune cell identity and activity, we established and extensively assessed a reference panel of 33 antibodies to cover major cell subsets, simultaneously quantifying activation and immune checkpoint molecules in a single assay. This assay enumerates &gt;= 98% of peripheral immune cells with &gt;= 4 positively identifying antigens. Robustness and reproducibility are demonstrated on multiple samples types, across two research centers and by orthogonal measurements. Using automated analysis, we identify stratifying immune signatures in bone marrow transplantation-associated graft-versus-host disease. Together, this validated workflow ensures comprehensive immunophenotypic analysis and data comparability and will accelerate biomarker discovery

Redox proteomics of the inflammatory secretome identifies a common set of redoxins and other glutathionylated proteins released in inflammation, influenza virus infection and oxidative stress

Protein cysteines can form transient disulfides with glutathione (GSH), resulting in the production of glutathionylated proteins, and this process is regarded as a mechanism by which the redox state of the cell can regulate protein function. Most studies on redox regulation of immunity have focused on intracellular proteins. In this study we have used redox proteomics to identify those proteins released in glutathionylated form by macrophages stimulated with lipopolysaccharide (LPS) after pre-loading the cells with biotinylated GSH. Of the several proteins identified in the redox secretome, we have selected a number for validation. Proteomic analysis indicated that LPS stimulated the release of peroxiredoxin (PRDX) 1, PRDX2, vimentin (VIM), profilin1 (PFN1) and thioredoxin 1 (TXN1). For PRDX1 and TXN1, we were able to confirm that the released protein is glutathionylated. PRDX1, PRDX2 and TXN1 were also released by the human pulmonary epithelial cell line, A549, infected with influenza virus. The release of the proteins identified was inhibited by the anti-inflammatory glucocorticoid, dexamethasone (DEX), which also inhibited tumor necrosis factor (TNF)-α release, and by thiol antioxidants (N-butanoyl GSH derivative, GSH-C4, and N-acetylcysteine (NAC), which did not affect TNF-α production. The proteins identified could be useful as biomarkers of oxidative stress associated with inflammation, and further studies will be required to investigate if the extracellular forms of these proteins has immunoregulatory functions

3D printed tissue engineered model for bone invasion of oral cancer

Recent advances in three-dimensional printing technology have led to a rapid expansion of its applications in tissue engineering. The present study was designed to develop and characterize an in vitro multi-layered human alveolar bone, based on a 3D printed scaffold, combined with tissue engineered oral mucosal model. The objective was to incorporate oral squamous cell carcinoma (OSCC) cell line spheroids to the 3D model at different anatomical levels to represent different stages of oral cancer. Histological evaluation of the 3D tissue model revealed a tri-layered structure consisting of distinct epithelial, connective tissue, and bone layers; replicating normal oral tissue architecture. The mucosal part showed a well-differentiated stratified oral squamous epithelium similar to that of the native tissue counterpart, as demonstrated by immunohistochemistry for cytokeratin 13 and 14. Histological assessment of the cancerous models demonstrated OSCC spheroids at three depths including supra-epithelial level, sub-epithelial level, and deep in the connective tissue-bone interface. The 3D tissue engineered composite model closely simulated the native oral hard and soft tissues and has the potential to be used as a valuable in vitro model for the investigation of bone invasion of oral cancer and for the evaluation of novel diagnostic or therapeutic approaches to manage OSCC in the future

Survey of both hepatitis B virus (HBsAg) and hepatitis C virus (HCV-Ab) coinfection among HIV positive patients

<p>Abstract</p> <p>Background</p> <p>HIV, HBVand HCV is major public health concerns. Because of shared routes of transmission, HIV-HCV coinfection and HIV-HBV coinfection are common. HIV-positive individuals are at risk of coinfection with HBV and HCV infections. The prevalence rates of coinfection with HBV and HCV in HIV-patients have been variable worldwide depending on the geographic regions, and the type of exposure.</p> <p>Aim</p> <p>This study aimed to examine HBV and HCV coinfection serologically and determine the shared and significant factors in the coinfection of HIV-positive patients.</p> <p>Methods</p> <p>This descriptive, cross-sectional study was carried out on 391 HIV-positive patients including 358 males and 33 females in Lorestan province, west Iran, to survey coinfection with HBsAg and anti-HCV. The retrospective demographic data of the subjects was collected and the patients' serums were analyzed by ELISA kits including HBsAg and anti-HCV. The collected data was analyzed with SPSS software (15) and Chi-square. Fisher's exact test with 5% error intervals was used to measure the correlation of variables and infection rates.</p> <p>Results</p> <p>The results of the study indicated that the prevalence of coinfection in HIV-positive patients with hepatitis viruses was 94.4% (370 in 391), out of whom 57 (14.5%) cases were HBsAg positive, 282 (72%) cases were anti-HCV positive, and 31 (7.9%) cases were both HBsAg and anti-HCV positive.</p> <p>Conclusion</p> <p>There was a significant correlation between coinfection with HCV and HBV and/or both among HIV-positive patients depending on different variables including sex, age, occupation, marital status, exposure to risk factors.(p < 0.001).</p

Oxygen matters: tissue culture oxygen levels affect mitochondrial function and structure as well as responses to HIV viroproteins

Mitochondrial dysfunction is implicated in a majority of neurodegenerative disorders and much study of neurodegenerative disease is done on cultured neurons. In traditional tissue culture, the oxygen level that cells experience is dramatically higher (21%) than in vivo conditions (1–11%). These differences can alter experimental results, especially, pertaining to mitochondria and oxidative metabolism. Our results show that primary neurons cultured at physiological oxygen levels found in the brain showed higher polarization, lower rates of ROS production, larger mitochondrial networks, greater cytoplasmic fractions of mitochondria and larger mitochondrial perimeters than those cultured at higher oxygen levels. Although neurons cultured in either physiological oxygen or atmospheric oxygen exhibit significant increases in mitochondrial reactive oxygen species (ROS) production when treated with the human immunodeficiency virus (HIV) virotoxin trans-activator of transcription, mitochondria of neurons cultured at physiological oxygen underwent depolarization with dramatically increased cell death, whereas those cultured at atmospheric oxygen became hyperpolarized with no increase in cell death. Studies with a second HIV virotoxin, negative regulation factor (Nef), revealed that Nef treatment also increased mitochondrial ROS production for both the oxygen conditions, but resulted in mitochondrial depolarization and increased death only in neurons cultured in physiological oxygen. These results indicate a role for oxidative metabolism in a mechanism of neurotoxicity during HIV infection and demonstrate the importance of choosing the correct, physiological, culture oxygen in mitochondrial studies performed in neurons

Bi-directional cell-pericellular matrix interactions direct stem cell fate

Modifiable hydrogels have revealed tremendous insight into how physical characteristics of cells’ 3D environment drive stem cell lineage specification. However, in native tissues, cells do not passively receive signals from their niche. Instead they actively probe and modify their pericellular space to suit their needs, yet the dynamics of cells’ reciprocal interactions with their pericellular environment when encapsulated within hydrogels remains relatively unexplored. Here, we show that human bone marrow stromal cells (hMSC) encapsulated within hyaluronic acid-based hydrogels modify their surroundings by synthesizing, secreting and arranging proteins pericellularly or by degrading the hydrogel. hMSC’s interactions with this local environment have a role in regulating hMSC fate, with a secreted proteinaceous pericellular matrix associated with adipogenesis, and degradation with osteogenesis. Our observations suggest that hMSC participate in a bi-directional interplay between the properties of their 3D milieu and their own secreted pericellular matrix, and that this combination of interactions drives fate