Sebaceous Carcinoma of the Eyelid

Sebaceous gland carcinoma of the eyelid is a very rare, slow growing tumor arising from the meibomian glands. In contrast to squamous cell carcinoma and basal cell carcinoma which arise frequently from the lower lid, sebaceous carcinoma arises from the upper lid where meibomian glands are more numerous. We present a case of sebaceous carcinoma in an elderly lady who presented with a slow growing tumor in the lateral third of the lower lid, without any lymph node metastasis. The tumor was treated by wide excision and the eyelid was reconstructed by Tenzel semilunar flap

Development of Carbon Fibre Metal Laminates (CFML): Design, Fabrication and Characterisation

Abstract Fibre Metal Laminates (FMLs) are hybrid materials consisting of metal layers bonded to fibre-reinforced polymer layers. CFML is an FML developed at NAL consisting of thin aluminum foil combined with carbon-epoxy and glass-epoxy prepreg materials. CFML is proposed as the candidate material for the leading edges of wing and empennage of an aircraft as it has superior characteristics in terms of shape retention (due to highly linearly elastic material like carbon/epoxy), energy absorption capability (due to layered structure and plastic deformation), lightning protection (due to the presence of aluminum layers), and also due to its cost effectiveness (lightweight construction and simple production techniques). An important design issue is the internal residual stresses built into the laminate during curing due to differential coefficients of thermal expansion of the different material systems. This report discusses the methods and issues involved in the fabrication of CFML. CFML laminates were fabricated and Tensile, Compression, ILSS and Flexure testing of standard specimens for different lay-ups were done. The failure modes exhibited during these tests indicate that these materials could be better in energy absorption. However, these conclusions need to be validated with the experiments to quantify their energy absorption capability

Active Vibration Control of Structures using an Impedance Matching Control Technique

Active vibration control of structures has gained a lot of interest in recent years. This paper presents an active vibration control methodology of a structure using piezoelectric actuators. The proposed methodology is useful in practical applications where the system to be controlled is difficult to model due to the presence of complex boundary conditions. The impedance matching control technique uses a power flow approach wherein the controller is designed such that the power flow into the structure is minimized. The system transfer function is obtained from the experimental collocated actuator/sensor pair data using Eigen Realisation Algorithm (ERA). The controller is designed for the system transfer function according to impedance matching theory. The above approach is targeted towards the vibration control of wind tunnel stings, which suffer from flow-induced vibration. A wind tunnel sting model is designed and fabricated for this study. The real time implementation of the impedance matching controller has been carried out using dSPACE® Digital Signal Processor (DSP) card. The results are encouraging and demonstrate the feasibility of applying this technique in the wind tunne

Development of CGLARE: Design, Fabrication and Characterisation

Fibre Metal Laminates (FMLs) are hybrid materials consisting of metal layers bonded to fibre-reinforced polymer layers. CGLARE is an FML developed at NAL consisting of thin aluminum foil combined with carbon-epoxy and glass-epoxy prepreg materials. CGLARE is proposed as the candidate material for the leading edges of wing and empennage of an aircraft as it has superior characteristics in terms of shape retention (due to highly linearly elastic material like carbon/epoxy), energy absorption capability (due to layered structure and plastic deformation), lightning protection (due to the presence of aluminum layers), and also due to its cost effectiveness (lightweight construction and simple production techniques). This paper describes the issues regarding the development of CGLARE such as surface preparation of aluminum foils and bonding of aluminum with glass. Tensile, Compression, ILSS and Flexure testing of ASTM standard CGLARE specimens for different layups have been done. An important design issue is the internal residual stresses built into the laminate during curing due to differential coefficients of thermal expansion of the different material systems. The paper presents these results that indicate some properties of these material systems that could be exploited for energy absorption in the leading edges of the aircraft

Propofol induces MAPK/ERK cascade dependant expression of cFos and Egr-1 in rat hippocampal slices

Background: Propofol is a commonly used intravenous anesthetic agent, which produce rapid induction of and recovery from general anesthesia. Numerous clinical studies reported that propofol can potentially cause amnesia and memory loss in human subjects. The underlying mechanism for this memory loss is unclear but may potentially be related to the induction of memory-associated genes such as c-Fos and Egr-1 by propofol. This study explored the effects of propofol on c-Fos and Egr-1 expression in rat hippocampal slices. Findings: Hippocampal brain slices were exposed to varying concentrations of propofol at multiple time intervals. The transcription of the immediate early genes, c-Fos and Egr-1, was quantified using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). MAPK/ERK inhibitors were used to investigate the mechanism of action. We demonstrate that propofol induced the expression of c-Fos and Egr-1 within 30 and 60 min of exposure time. At 16.8 μM concentration, propofol induced a 110% increase in c-Fos transcription and 90% decrease in the transcription of Egr-1. However, at concentrations above 100 μM, propofol failed to induce expression of c-Fos but did completely inhibit the transcription of Egr-1. Propofol-induced c-Fos and Egr-1 transcription was abolished by inhibitors of RAS, RAF, MEK, ERK and p38-MAPK in the MAPK/ERK cascade. Conclusions: Our study shows that clinically relevant concentrations of propofol induce c-Fos and down regulated Egr-1 expression via an MAPK/ERK mediated pathway. We demonstrated that propofol induces a time and dose dependant transcription of IEGs c-Fos and Egr-1 in rat hippocampal slices. We further demonstrate for the first time that propofol induced IEG expression was mediated via a MAPK/ERK dependant pathway. These novel findings provide a new avenue to investigate transcription-dependant mechanisms and suggest a parallel pathway of action with an unclear role in the activity of general anesthetics

Gaps in clinical research in frontotemporal dementia: A call for diversity and disparities–focused research

Frontotemporal dementia (FTD) is one of the leading causes of dementia before age 65 and often manifests as abnormal behavior (in behavioral variant FTD) or language impairment (in primary progressive aphasia). FTD's exact clinical presentation varies by culture, language, education, social norms, and other socioeconomic factors; current research and clinical practice, however, is mainly based on studies conducted in North America and Western Europe. Changes in diagnostic criteria and procedures as well as new or adapted cognitive tests are likely needed to take into consideration global diversity. This perspective paper by two professional interest areas of the Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment examines how increasing global diversity impacts the clinical presentation, screening, assessment, and diagnosis of FTD and its treatment and care. It subsequently provides recommendations to address immediate needs to advance global FTD research and clinical practice

Acetylation Regulates WRN Catalytic Activities and Affects Base Excision DNA Repair

Background: The Werner protein (WRN), defective in the premature aging disorder Werner syndrome, participates in a number of DNA metabolic processes, and we have been interested in the possible regulation of its function in DNA repair by post-translational modifications. Acetylation mediated by histone acetyltransferases is of key interest because of its potential importance in aging, DNA repair and transcription. Methodology/Principal Findings: Here, we have investigated the p300 acetylation mediated changes on the function of WRN in base excision DNA repair (BER). We show that acetylation of WRN increases in cells treated with methyl methanesulfonate (MMS), suggesting that acetylation of WRN may play a role in response to DNA damage. This hypothesis is consistent with our findings that acetylation of WRN stimulates its catalytic activities in vitro and in vivo, and that acetylated WRN enhances pol b-mediated strand displacement DNA synthesis more than unacetylated WRN. Furthermore, we show that cellular exposure to the histone deacetylase inhibitor sodium butyrate stimulates long patch BER in wild type cells but not in WRN depleted cells, suggesting that acetylated WRN participates significantly in this process. Conclusion/Significance: Collectively, these results provide the first evidence for a specific role of p300 mediated WRN acetylation in regulating its function during BER

C. elegans EIF-3.K Promotes Programmed Cell Death through CED-3 Caspase

Programmed cell death (apoptosis) is essential for the development and homeostasis of metazoans. The central step in the execution of programmed cell death is the activation of caspases. In C. elegans, the core cell death regulators EGL-1(a BH3 domain-containing protein), CED-9 (Bcl-2), and CED-4 (Apaf-1) act in an inhibitory cascade to activate the CED-3 caspase. Here we have identified an additional component eif-3.K (eukaryotic translation initiation factor 3 subunit k) that acts upstream of ced-3 to promote programmed cell death. The loss of eif-3.K reduced cell deaths in both somatic and germ cells, whereas the overexpression of eif-3.K resulted in a slight but significant increase in cell death. Using a cell-specific promoter, we show that eif-3.K promotes cell death in a cell-autonomous manner. In addition, the loss of eif-3.K significantly suppressed cell death-induced through the overexpression of ced-4, but not ced-3, indicating a distinct requirement for eif-3.K in apoptosis. Reciprocally, a loss of ced-3 suppressed cell death induced by the overexpression of eif-3.K. These results indicate that eif-3.K requires ced-3 to promote programmed cell death and that eif-3.K acts upstream of ced-3 to promote this process. The EIF-3.K protein is ubiquitously expressed in embryos and larvae and localizes to the cytoplasm. A structure-function analysis revealed that the 61 amino acid long WH domain of EIF-3.K, potentially involved in protein-DNA/RNA interactions, is both necessary and sufficient for the cell death-promoting activity of EIF-3.K. Because human eIF3k was able to partially substitute for C. elegans eif-3.K in the promotion of cell death, this WH domain-dependent EIF-3.K-mediated cell death process has potentially been conserved throughout evolution

Structural and Functional Evaluation of C. elegans Filamins FLN-1 and FLN-2

Filamins are long, flexible, multi-domain proteins composed of an N-terminal actin-binding domain (ABD) followed by multiple immunoglobulin-like repeats (IgFLN). They function to organize and maintain the actin cytoskeleton, to provide scaffolds for signaling components, and to act as mechanical force sensors. In this study, we used transcript sequencing and homology modeling to characterize the gene and protein structures of the C. elegans filamin orthologs fln-1 and fln-2. Our results reveal that C. elegans FLN-1 is well conserved at the sequence level to vertebrate filamins, particularly in the ABD and several key IgFLN repeats. Both FLN-1 and the more divergent FLN-2 colocalize with actin in vivo. FLN-2 is poorly conserved, with at least 23 IgFLN repeats interrupted by large regions that appear to be nematode-specific. Our results indicate that many of the key features of vertebrate filamins are preserved in C. elegans FLN-1 and FLN-2, and suggest the nematode may be a very useful model system for further study of filamin function