Interface bonding of a ferromagnetic/semiconductor junction : a photoemission study of Fe/ZnSe(001)

We have probed the interface of a ferromagnetic/semiconductor (FM/SC) heterojunction by a combined high resolution photoemission spectroscopy and x-ray photoelectron diffraction study. Fe/ZnSe(001) is considered as an example of a very low reactivity interface system and it expected to constitute large Tunnel Magnetoresistance devices. We focus on the interface atomic environment, on the microscopic processes of the interface formation and on the iron valence-band. We show that the Fe contact with ZnSe induces a chemical conversion of the ZnSe outermost atomic layers. The main driving force that induces this rearrangement is the requirement for a stable Fe-Se bonding at the interface and a Se monolayer that floats at the Fe growth front. The released Zn atoms are incorporated in substitution in the Fe lattice position. This formation process is independent of the ZnSe surface termination (Zn or Se). The Fe valence-band evolution indicates that the d-states at the Fermi level show up even at submonolayer Fe coverage but that the Fe bulk character is only recovered above 10 monolayers. Indeed, the Fe 1-band states, theoretically predicted to dominate the tunneling conductance of Fe/ZnSe/Fe junctions, are strongly modified at the FM/SC interface.Comment: 23 pages, 5 figures, submitted to Physical review

Extending the frontiers of mass spectrometric instrumentation and methods

Ion mobility coupled to mass spectrometry is fast becoming a common tool to analyze biological systems. A novel ion trap — ion mobility — mass spectrometer was characterized primarily using ubiquitin, cytochrome c, and YbhB proteins. The time resolved protein ion heating between the ion trap and drift tube is described. Besides the novel instrument, mass spectrometric methods were developed for the rapid analysis of coal using direct analysis in real time

Molecular classification of a complex structural rearrangement of the RB1 locus in an infant with sporadic, isolated, intracranial, sellar region retinoblastoma

Retinoblastoma is a childhood cancer of the retina involving germline or somatic alterations of the RB Transcriptional Corepressor 1 gene, RB1. Rare cases of sellar-suprasellar region retinoblastoma without evidence of ocular or pineal tumors have been described. A nine-month-old male presented with a sellar-suprasellar region mass. Histopathology showed an embryonal tumor with focal Flexner-Wintersteiner-like rosettes and loss of retinoblastoma protein (RB1) expression by immunohistochemistry. DNA array-based methylation profiling confidently classified the tumor as pineoblastoma group A/intracranial retinoblastoma. The patient was subsequently enrolled on an institutional translational cancer research protocol and underwent comprehensive molecular profiling, including paired tumor/normal exome and genome sequencing and RNA-sequencing of the tumor. Additionally, Pacific Biosciences (PacBio) Single Molecule Real Time (SMRT) sequencing was performed from comparator normal and disease-involved tissue to resolve complex structural variations. RNA-sequencing revealed multiple fusions clustered within 13q14.1-q21.3, including a novel in-frame fusion of RB1-SIAH3 predicted to prematurely truncate the RB1 protein. SMRT sequencing revealed a complex structural rearrangement spanning 13q14.11-q31.3, including two somatic structural variants within intron 17 of RB1. These events corresponded to the RB1-SIAH3 fusion and a novel RB1 rearrangement expected to correlate with the complete absence of RB1 protein expression. Comprehensive molecular analysis, including DNA array-based methylation profiling and sequencing-based methodologies, were critical for classification and understanding the complex mechanism of RB1 inactivation in this diagnostically challenging tumor

Modifying effect of dual antiplatelet therapy on incidence of stent thrombosis according to implanted drug-eluting stent type

Aim To investigate the putative modifying effect of dual antiplatelet therapy (DAPT) use on the incidence of stent thrombosis at 3 years in patients randomized to Endeavor zotarolimus-eluting stent (E-ZES) or Cypher sirolimus-eluting stent (C-SES). Methods and results Of 8709 patients in PROTECT, 4357 were randomized to E-ZES and 4352 to C-SES. Aspirin was to be given indefinitely, and clopidogrel/ticlopidine for ≥3 months or up to 12 months after implantation. Main outcome measures were definite or probable stent thrombosis at 3 years. Multivariable Cox regression analysis was applied, with stent type, DAPT, and their interaction as the main outcome determinants. Dual antiplatelet therapy adherence remained the same in the E-ZES and C-SES groups (79.6% at 1 year, 32.8% at 2 years, and 21.6% at 3 years). We observed a statistically significant (P = 0.0052) heterogeneity in treatment effect of stent type in relation to DAPT. In the absence of DAPT, stent thrombosis was lower with E-ZES vs. C-SES (adjusted hazard ratio 0.38, 95% confidence interval 0.19, 0.75; P = 0.0056). In the presence of DAPT, no difference was found (1.18; 0.79, 1.77; P = 0.43). Conclusion A strong interaction was observed between drug-eluting stent type and DAPT use, most likely prompted by the vascular healing response induced by the implanted DES system. These results suggest that the incidence of stent thrombosis in DES trials should not be evaluated independently of DAPT use, and the optimal duration of DAPT will likely depend upon stent type (Clinicaltrials.gov number NCT00476957

The Immune System in Stroke

Stroke represents an unresolved challenge for both developed and developing countries and has a huge socio-economic impact. Although considerable effort has been made to limit stroke incidence and improve outcome, strategies aimed at protecting injured neurons in the brain have all failed. This failure is likely to be due to both the incompleteness of modelling the disease and its causes in experimental research, and also the lack of understanding of how systemic mechanisms lead to an acute cerebrovascular event or contribute to outcome. Inflammation has been implicated in all forms of brain injury and it is now clear that immune mechanisms profoundly influence (and are responsible for the development of) risk and causation of stroke, and the outcome following the onset of cerebral ischemia. Until very recently, systemic inflammatory mechanisms, with respect to common comorbidities in stroke, have largely been ignored in experimental studies. The main aim is therefore to understand interactions between the immune system and brain injury in order to develop novel therapeutic approaches. Recent data from clinical and experimental research clearly show that systemic inflammatory diseases -such as atherosclerosis, obesity, diabetes or infection - similar to stress and advanced age, are associated with dysregulated immune responses which can profoundly contribute to cerebrovascular inflammation and injury in the central nervous system. In this review, we summarize recent advances in the field of inflammation and stroke, focusing on the challenges of translation between pre-clinical and clinical studies, and potential anti-inflammatory/immunomodulatory therapeutic approaches

Impact of COVID 19 on Higher Learning Community

The societal upheaval related to the COVID-19 pandemic was far-reaching and continues to impact individuals in both personal and professional ways. Attempts to mitigate the spread of COVID-19 included quarantining at home and temporarily closing schools, businesses, and other public spaces. As these disruptions of everyday life eased and restrictions were lifted, individuals and organizations alike are reflecting on the impact of the COVID-19 pandemic. The pandemic continues to have differential effects across industry types. Higher education institutions (HEIs) are a particularly unique example as they serve as both an organization navigating employee needs as well as providing learning services and support to students who may also be working outside of classes. This study aimed to investigate the unique impact of the pandemic on employee and student experiences within a HEI. As part of a larger study, the current researchers sought to understand how higher education professionals (faculty and staff) and employed students navigated work during and since the peak of the pandemic. To measure the employment impact of COVID-19, a survey consisting of 43 items from established scales measuring work-family conflict (WFC and FWC), job demands, job autonomy, job stress, job insecurity, perceived supervisor and organizational support (PSS, POS), work engagement, and job satisfaction was administered to university employed staff (n = 133), university faculty (n = 118), and off-campus employed students (n = 379). ANOVAs with Welch homogeneity corrections were conducted to account for unequal variances between samples. Results revealed significant differences among students, faculty, and staff in their experiences of WFC, FWC, job demands, job autonomy, job stress, and work engagement. Students reported the highest levels of conflict and stress, and the lowest levels of autonomy and job satisfaction. Faculty and staff exhibited higher work engagement and job satisfaction despite experiencing high job demands, perhaps in part related to their higher reported levels of job autonomy and supervisor support. These findings underscore the urgency for targeted interventions to alleviate identified challenges. University-based support measures are recommended to help manage ongoing competing demands and work-related stress. These resources should be customized to meet the specific needs of each group and go beyond generalized campus counseling services and EAPs, towards a culture that demonstrates that the health and wellbeing of the campus community is valued. The data offer a comprehensive understanding of the complex impact of the COVID-19 pandemic on different employment groups within higher education, thereby extending the current literature

Impact of interleukin-6 on hypoxia-induced pulmonary hypertension and lung inflammation in mice

<p>Abstract</p> <p>Background</p> <p>Inflammation may contribute to the pathogenesis of various forms of pulmonary hypertension (PH). Recent studies in patients with idiopathic PH or PH associated with underlying diseases suggest a role for interleukin-6 (IL-6).</p> <p>Methods</p> <p>To determine whether endogenous IL-6 contributes to mediate hypoxic PH and lung inflammation, we studied IL-6-deficient (IL-6^-/-) and wild-type (IL-6^+/+) mice exposed to hypoxia for 2 weeks.</p> <p>Results</p> <p>Right ventricular systolic pressure, right ventricle hypertrophy, and the number and media thickness of muscular pulmonary vessels were decreased in IL-6^-/-mice compared to wild-type controls after 2 weeks' hypoxia, although the pressure response to acute hypoxia was similar in IL-6^+/+and IL-6^-/-mice. Hypoxia exposure of IL-6^+/+mice led to marked increases in IL-6 mRNA and protein levels within the first week, with positive IL-6 immunostaining in the pulmonary vessel walls. Lung IL-6 receptor and gp 130 (the IL-6 signal transducer) mRNA levels increased after 1 and 2 weeks' hypoxia. In vitro studies of cultured human pulmonary-artery smooth-muscle-cells (PA-SMCs) and microvascular endothelial cells revealed prominent synthesis of IL-6 by PA-SMCs, with further stimulation by hypoxia. IL-6 also markedly stimulated PA-SMC migration without affecting proliferation. Hypoxic IL-6^-/-mice showed less inflammatory cell recruitment in the lungs, compared to hypoxic wild-type mice, as assessed by lung protein levels and immunostaining for the specific macrophage marker F4/80, with no difference in lung expression of adhesion molecules or cytokines.</p> <p>Conclusion</p> <p>These data suggest that IL-6 may be actively involved in hypoxia-induced lung inflammation and pulmonary vascular remodeling in mice.</p

Nongenomic oestrogen signalling in oestrogen receptor negative breast cancer cells: a role for the angiotensin II receptor AT1

INTRODUCTION: Oestrogens can mediate some of their cell survival properties through a nongenomic mechanism that involves the mitogen-activated protein kinase (MAPK) pathway. The mechanism of this rapid signalling and its dependence on a membrane bound oestrogen receptor (ER), however, remains controversial. The role of G-protein-coupled receptor and epidermal growth factor (EGF) receptor in an ER-independent signalling pathway modulated by oestrogen was investigated. METHODS: ER-positive and ER-negative breast cancer cell lines (MCF-7 and SKBR3) and primary breast cancer cell cultures were used in this study. Cell proliferation was assessed using standard MTT assays. Protein and cAMP levels were detected by Western blotting and ELISA, respectively. Antigen localization was performed by immunocytochemistry, immunohistochemistry and immunofluorescence. Protein knockdown was achieved using small interfering RNA technologies. RESULTS: EGF and oestrogen, alone and in combination, induced cell proliferation and phosphorylation of MAPK proteins Raf and ERK (extracellular signal regulated kinase)1/2 in both ER-negative SKBR3 and ER-positive MCF-7 human breast cancer cell lines. Increased Raf phosphorylation was also observed in primary human breast cultures derived from ER-positive and ER-negative breast tumours. Oestrogen induced an increase in intracellular cAMP in ER-negative SKBR3 human breast cancer cells. Oestrogen-mediated cell growth and phosphorylation of MAPK was modified by the EGF receptor antagonist AG1478, the G-protein antagonist pertussis toxin, and the angiotensin II receptor antagonist saralasin. Knockdown of angiotensin II type 1 receptor (AT1) protein expression with small interfering RNA attenuated oestrogen-induced Raf phosphorylation in ER-negative cells. AT1 receptor was found to be expressed in the cell membrane of breast tumour epithelial cells. CONCLUSION: These findings provide evidence that, in breast cancer cells, oestrogen can signal through AT1 to activate early cell survival mechanisms in an ER-independent manner