Principals Preparation Program: Managing The Learning Environment Using ELCC Standards

School principals need to be well prepared to manage school facilities assigned to their care. Educational leadership programs can make best use of the Educational Leadership Constituent Council (ELCC) Standards to develop a course of study to address school facility management issues. Every standard has its facility implications that lead to designing course activities to prepare school principals to be facility managers. A school facility management course can be effectively delivered by meeting all ELCC Standards

Principal\u27s Preparation Program: Managing The Learning Environment Using ELCC Standards

School principals need to be well prepared to manage school facilities assigned to their care. Educational leadership programs can make best use of the Educational Leadership Constituent Council (ELCC) Standards to develop a course of study to address school facility management issues. Every standard has its facility implications that lead to designing course activities to prepare school principals to be facility managers. A school facility management course can be effectively delivered by meeting all ELCC Standards

A Randomized, Double-Blind, Placebo-Controlled Trial of a Polyphenol Botanical Blend on Sleep and Daytime Functioning

Despite the high prevalence of subclinical sleep disturbances, existing treatments are either potent prescription medications or over-the-counter supplements with minimal scientific support and numerous side effects. However, preliminary evidence shows that polyphenols such as rosmarinic acid and epigallocatechin gallate can support healthy sleep without significant side effects. Therefore, the present study examined whether a polyphenol botanical blend (PBB) could improve sleep and/or daytime functioning in individuals with subclinical sleep disturbances. A total of 89 individuals completed a double-blind, randomized trial of daily treatment with PBB (n = 43) or placebo (n = 46) 30 min before bed for 30 days. Participants were monitored for changes in sleep (by sleep diary and an activity tracker), mood, and neurocognitive functioning. After 30 days, PBB improved diary sleep quality (p = 0.008) and reduced insomnia severity (p = 0.044) when compared to placebo. No other changes in sleep outcomes were observed. Additionally, PBB did not impair neurocognitive functioning, and some improvement was noted in vigilant attention, working memory, and risk assessment. Among individuals with subclinical sleep disturbances, PBB improved sleep quality, insomnia severity, and neurocognitive functioning over placebo. These findings indicate that polyphenol compounds may be useful for improving certain aspects of sleep without compromising neurocognitive functioning

KAP-1 promotes resection of broken DNA ends not protected by γ-H2AX and 53BP1 in G1-phase lymphocytes

The resection of broken DNA ends is required for DNA double-strand break (DSB) repair by homologous recombination (HR) but can inhibit normal repair by nonhomologous end joining (NHEJ), the main DSB repair pathway in G(1)-phase cells. Antigen receptor gene assembly proceeds through DNA DSB intermediates generated in G(1)-phase lymphocytes by the RAG endonuclease. These DSBs activate ATM, which phosphorylates H2AX, forming γ-H2AX in flanking chromatin. γ-H2AX prevents CtIP from initiating resection of RAG DSBs. Whether there are additional proteins required to promote resection of these DNA ends is not known. KRAB-associated protein 1 (KAP-1) (TRIM28) is a transcriptional repressor that modulates chromatin structure and has been implicated in the repair of DNA DSBs in heterochromatin. Here, we show that in murine G(1)-phase lymphocytes, KAP-1 promotes resection of DSBs that are not protected by H2AX and its downstream effector 53BP1. In these murine cells, KAP-1 activity in DNA end resection is attenuated by a single-amino-acid change that reflects a KAP-1 polymorphism between primates and other mammalian species. These findings establish KAP-1 as a component of the machinery that can resect DNA ends in G(1)-phase cells and suggest that there may be species-specific features to this activity

Development of automated brightfield double In Situ hybridization (BDISH) application for HER2 gene and chromosome 17 centromere (CEN 17) for breast carcinomas and an assay performance comparison to manual dual color HER2 fluorescence In Situ hybridization (FISH)

BACKGROUND: Human epidermal growth factor receptor 2 (HER2) fluorescence in situ hybridization (FISH) is a quantitative assay for selecting breast cancer patients for trastuzumab therapy. However, current HER2 FISH procedures are labor intensive, manual methods that require skilled technologists and specialized fluorescence microscopy. Furthermore, FISH slides cannot be archived for long term storage and review. Our objective was to develop an automated brightfield double in situ hybridization (BDISH) application for HER2 gene and chromosome 17 centromere (CEN 17) and test the assay performance with dual color HER2 FISH evaluated breast carcinomas. METHODS: The BDISH assay was developed with the nick translated dinitrophenyl (DNP)-labeled HER2 DNA probe and DNP-labeled CEN 17 oligoprobe on the Ventana BenchMark(® )XT slide processing system. Detection of HER2 and CEN 17 signals was accomplished with the silver acetate, hydroquinone, and H(2)O(2 )reaction with horseradish peroxidase (HRP) and the fast red and naphthol phosphate reaction with alkaline phosphatise (AP), respectively. The BDISH specificity was optimized with formalin-fixed, paraffin-embedded xenograft tumors, MCF7 (non-amplified HER2 gene) and BT-474 (amplified HER2 gene). Then, the BDISH performance was evaluated with 94 routinely processed breast cancer tissues. Interpretation of HER2 and CEN 17 BDISH slides was conducted by 4 observers using a conventional brightfield microscope without oil immersion objectives. RESULTS: Sequential hybridization and signal detection for HER2 and CEN 17 ISH demonstrated both DNA targets in the same cells. HER2 signals were visualized as discrete black metallic silver dots while CEN 17 signals were detected as slightly larger red dots. Our study demonstrated a high consensus concordance between HER2 FISH and BDISH results of clinical breast carcinoma cases based on the historical scoring method (98.9%, Simple Kappa = 0.9736, 95% CI = 0.9222 – 1.0000) and the ASCO/CAP scoring method with the FISH equivocal cases (95.7%, Simple Kappa = 0.8993%, 95% CI = 0.8068 – 0.9919) and without the FISH equivocal cases (100%, Simple Kappa = 1.0000%, 95% CI = 1.0000 – 1.0000). CONCLUSION: Automated BDISH applications for HER2 and CEN 17 targets were successfully developed and it might be able to replace manual two-color HER2 FISH methods. The application also has the potential to be used for other gene targets. The use of BDISH technology allows the simultaneous analyses of two DNA targets within the context of tissue morphological observation

The inferior intercavernous sinus : an anatomical study with application to trans-sphenoidal approaches to the pituitary gland

CITATION: Wahl, L. et al. 2020. The inferior intercavernous sinus: An anatomical study with application to trans-sphenoidal approaches to the pituitary gland. Clinical Neurology and Neurosurgery, 196, doi:10.1016/j.clineuro.2020.106000.The original publication is available at https://www.sciencedirect.com/journal/clinical-neurology-and-neurosurgeryObjectives: The inferior intercavernous sinus is located below the pituitary gland in the sella turcica. Its presence has been controversial among anatomists because it is not always found on radiological imaging or during cadaveric dissections; however, it is becoming a better-known structure in the neurosurgical and radiological fields, specifically with respect to transsphenoidal surgery. Therefore, the present study was performed to better elucidate this structure at the skull base. Patients and methods: Fifty adult, latex injected cadavers underwent dissection. The presence or absence of the inferior cavernous sinus was evaluated and when present, measurements of its width and length were made. Its connections with other intradural venous sinuses were also documented. Results: An inferior intercavernous sinus was identified in 26 % of specimens. In all specimens, it communicated with the left and right cavernous sinus. The average width and length were 3 mm and 9.5 mm, respectively. In the sagittal plane, the inferior intercavernous sinus was positioned anteriorly in 31 %, at the nadir of the sella turcica in 38 %, and slightly posterior to the nadir of the sella turcica in 31 %. In two specimens (15.4 %), the sinus was plexiform in its shape. In one specimen a diploic vein connected the basilar venous plexus to the inferior intercavernous sinus on its deep surface. Conclusion: An improved understanding of the variable anatomy of the inferior intercavernous sinus is important in pathological, surgical, and radiological cases.https://www.sciencedirect.com/science/article/pii/S0303846720303437?via%3DihubPublishers versio

Global error analysis and inertial manifold reduction

Four types of global error for initial value problems are considered in a common framework. They include classical forward error analysis and shadowing error analysis together with extensions of both to include rescaling of time. To determine the amplificatioh of the local error that bounds the global error we present a linear analysis similar in spirit to condition number estimation for linear systems of equations. We combine these ideas with techniques for dimension reduction of differential equations via a boundary value formulation of numerical inertial manifold reduction. These global error concepts are exercised to illustrate their utility on the Lorenz equations and inertial manifold reductions of the Kuramoto-Sivashinsky equation. (C) 2016 Elsevier B.V. All rights reserved

Massive Tau Neutrino and SN 1987a

The emission of \MeV-mass tau neutrinos from newly formed neutron stars is considered in a simple, but accurate, model based upon the diffusion approximation. The tau-neutrinosphere temperature is found to increase with mass so that emission of massive tau neutrinos is not suppressed by the Boltzmann factor previously used, (\mnu /T_\nu )^{1.5}\exp(-\mnu/T_{\nu}), where T_{\nu}\sim 4\MeV -8\MeV. If the tau neutrino decays to electron neutrinos, then for short lifetimes (\taunu\la10^{-3}\sec) the location of both the tau and electron neutrinospheres can be affected, and, for very short lifetimes (\tau_\nu \la 10^{-6}\sec) its temperature falls below 1\MeV, in conflict with neutrino observations of Supernova 1987A (SN 87A). Using our results, we revise limits to the mass/lifetime of an \MeV-mass tau neutrino based upon SN 87A. Our constraints, together with bounds based upon primordial nucleosynthesis and the laboratory mass limit of around 30\MeV, exclude the possibility of a tau neutrino more massive than 0.4\MeV if the dominant decay mode is radiative. Finally, we speculate on the possible role a 15\MeV -25\MeV tau neutrino might play in the supernova explosion itself.Comment: 14 LATEX pages, 11 Figures available on request, FNAL-Pub-94/001-

Tissue microarray analysis of eIF4E and its downstream effector proteins in human breast cancer

Correction to Kleiner HE, Krishnan P, Tubbs J, Smith M, Meschonat C, Shi R, Lowery-Nordberg M, Adegboyega P, Unger M, Cardelli J et al: Tissue microarray analysis of eIF4E and its downstream effector proteins in human breast cancer. J Exp Clin Cancer Res 2009, 28:5

High-Definition DNA Methylation Profiles from Breast and Ovarian Carcinoma Cell Lines with Differing Doxorubicin Resistance

Acquired drug resistance represents a frequent obstacle which hampers efficient chemotherapy of cancers. The contribution of aberrant DNA methylation to the development of drug resistant tumor cells has gained increasing attention over the past decades. Hence, the objective of the presented study was to characterize DNA methylation changes which arise from treatment of tumor cells with the chemotherapeutic drug doxorubicin. DNA methylation levels from CpG islands (CGIs) linked to twenty-eight genes, whose expression levels had previously been shown to contribute to resistance against DNA double strand break inducing drugs or tumor progression in different cancer types were analyzed. High-definition DNA methylation profiles which consisted of methylation levels from 800 CpG sites mapping to CGIs around the transcription start sites of the selected genes were determined. In order to investigate the influence of CGI methylation on the expression of associated genes, their mRNA levels were investigated via qRT-PCR. It was shown that the employed method is suitable for providing highly accurate methylation profiles, comparable to those obtained via clone sequencing, the gold standard for high-definition DNA methylation studies. In breast carcinoma cells with acquired resistance against the double strand break inducing drug doxorubicin, changes in methylation of specific cytosines from CGIs linked to thirteen genes were detected. Moreover, similarities between methylation profiles obtained from breast and ovarian carcinoma cell lines with acquired doxorubicin resistance were found. The expression levels of a subset of analyzed genes were shown to be linked to the methylation levels of the analyzed CGIs. Our results provide detailed DNA methylation information from two separate model systems for acquired doxorubicin resistance and suggest the occurrence of similar methylation changes in both systems upon exposure to the drug