DYNAMIC BEHAVIOUR OF PAPER HONEYCOMB SANDWICH PANELS

Low velocity impact tests have been conducted on paper honeycomb sandwich panels. Two panel thicknesses with span length of 100 mm are used; these are 35 mm and 41 mm, respectively. The dynamic behavior of each paper honeycomb thickness is investigated using two types of indentors: hemispherical and bar. The effect of indentor, and specimen length are studied. This includes the pattern of loaddisplacement curve collapse load and energy absorbed. It concludes that the dynamic collapse load on 41 mm thickness for hemispherical indentor increases by 5% compared with 35 mm. The impact energy absorbed for hemispherical indentor increases by 36%

Gastrointestinal Stromal Tumors: a Rare Neoplasm Presenting with Gastrointestinal Bleeding

Gastrointestinal stromal tumors (GIST) are rare tumors of the gastrointestinal (GI) tract that arise from primitive mesenchymal cells. GISTs occur throughout the GI tract but are usually located in the stomach and small intestine. GISTs are known with myoid, neural or mixed features of differentiation. Clinical findings are gastrointestinal bleeding, abdominal pain, and weight loss. GISTs express a heterogeneous clinical course not easily predicted. The histologic features that correlate best with development of recurrence and metastasis are mitotic activity, tumor size and the presence of tumor necrosis and most recently, mutation in the c-kit gene. Some authors specifically use the term GIST to refer to only those mesenchymal tumors that express CD117, whereas others believe that the diagnosis can be made in the absence of CD117 positivity based on clinical and morphologic features. Surgical resection remains the treatment of choice, since chemotherapy and radiation are ineffective. Long-term follow-up is imperative and recurrence rates are high. We report the case of a 60 years old female patient who presented with intermittent melena, chronic dyspepsia, and anemia. Upper digestive tract endoscopy showed a submucosal tumor, broad-based, centrally ulcerated, projection of >5 cm in the gastric corpus-antral wall as the cause of the upper gastrointestinal bleeding. Endoscopic biopsies were negative for neoplastic changes. After triple eradication therapy of Helicobacter pylori and treatment continued with proton pump inhibitor agent, the patient underwent distal gastrectomy with Billroth-I reconstruction. Histopatological studies on the surgical resection specimen revealed a GIST of smooth muscle with spindle cell, no evidence of mitotic activity but of uncertain biological behavior. One year after surgery the patient is was improved with no signs of residual Malignancy. However, metastases were found later in the liver in the next two year

Pre- and Posttranslational Regulation of Β-Endorphin Biosynthesis in the CNS: Effects of Chronic Naltrexone Treatment

There appear to be two anatomically distinct Β-endorphin (ΒE) pathways in the brain, the major one originating in the arcuate nucleus of the hypothalamus and a smaller one in the area of the nucleus tractus solitarius (NTS) of the caudal medulla. Previous studies have shown that these two proopiomelanocortin (POMC) systems may be differentially regulated by chronic morphine treatment, with arcuate cells down-regulated and NTS cells unaffected. In the present experiments, we examined the effects of chronic opiate antagonist treatment on ΒE biosynthesis across different CNS regions to assess whether the arcuate POMC system would be regulated in the opposite direction to that seen after opiate agonist treatment and to determine whether different ΒE-containing areas might be differentially regulated. Male adult rats were administered naltrexone (NTX) by various routes for 8 days (subcutaneous pellets, osmotic minipumps, or repeated intraperitoneal injections). Brain and spinal cord regions were assayed for total ΒE-ir, different molecular weight immunoreactive Β-endorphin (ΒE-ir) peptides, and POMC mRNA. Chronic NTX treatment, regardless of the route of administration, reduced total ΒE-ir concentrations by 30–40% in diencephalic areas (the arcuate nucleus, the remaining hypothalamus, and the thalamus) and the midbrain, but had no effect on ΒE-ir in the NTS or any region of the spinal cord. At the same time, NTX pelleting increased POMC mRNA levels in the arcuate to ∼ 140% of control values. These data suggest that arcuate POMC neurons are up-regulated after chronic NTX treatment (whereas NTS and spinal cord systems remain unaffected) and that they appear to be under tonic inhibition by endogenous opioids. Chromatographic analyses demonstrated that, after chronic NTX pelleting, the ratio of full length ΒE 1–31 to more processed ΒE-ir peptides (i.e., ΒE 1–27 and ΒE 1–26 ) tended to increase in a dose-dependent manner in diencephalic areas. Because ΒE 1–31 is the only POMC product that possesses opioid agonist properties, and ΒE 1–27 has been posited to function as an endogenous anatgonist of ΒE 1–31 , the NTX-induced changes in the relative concentrations of ΒE 1–31 and ΒE 1–27 /ΒE 1–26 may represent a novel regulatory mechanism of POMC cells to alter the opioid signal in the synapse.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65603/1/j.1471-4159.1993.tb05820.x.pd

Design, synthesis, docking and mechanistic studies of new thiazolyl/thiazolidinylpyrimidine-2,4-dione antiproliferative agents

In this article, we display on the synthesis and biological evaluation of a new series of thiazolylpyrimidine 3a-l and thiazolidinylpyrimidine derivatives 5a-e. The structures of the new compounds were confirmed by using different spectral techniques including NMR, IR, mass spectroscopy in addition to elemental analyses. The cell viability of the new compounds was assessed against normal human mammary gland epithelial (MCF-10A) cell line. Data revealed that none of the compounds examined exhibited cytotoxic effects, and the cell viability for the compounds examined at 50 µM was greater than 87%. The antiproliferative activity of 3a-l and 5a-e was evaluated against four human cancer cell lines where the compounds showed promising activity. The most potent derivatives were compounds 3a, 3c, 3f, 3i, and 5b with GI$_{50}$ values ranging from 0.90 µM to 1.70 µM against the four cancer cell lines in comparison to doxorubicin (GI$_{50}$ = 1.10 µM). Compounds 3a, 3c and 3i showed potent antiproliferative activity with dual inhibitory action against EGFR and BRAF$^{V600E}$. Compounds 3a, 3c, and 3i demonstrated promising AutoDock scores towards EGFR and BRAF$^{V600E}$ with values of − 9.1 and − 8.6, −9.0 and − 8.5, and − 8.4 and − 8.0 kcal/mol, respectively. The physicochemical and pharmacokinetic characteristics of 3a, 3c, and 3i were anticipated, demonstrating their oral bioavailability

Preparation and Characterization of pH- and Temperature-responsive by Different Composition Chitosan-P(MAA-co-NIPAM) Hydrogel for Drug Delivery System / S. Z. M. Rasib ...[et al.]

In this paper, (chitosan-poly(methacrylic acid-co-N-isopropylacrylamide)) [Chitosan-P(MAA-co-NIPAM)], a multi-responsive hydrogel was successfully fabricated by free-radical polymerization in aqueous media. Chitosan was crosslinked with P(MAA-co-NIPAM) network as a suggestion to improve the efficiency of chitosan as a drug carrier. Due to the hydrophilic and hydrophobic characteristics of MAA and NIPAM monomers presented in the network, the swelling behaviour at different pH and temperature was investigated in this paper. The composition, morphological stability, swelling behavior at various pH and temperature environment of the Chitosan-P(MAA-co-NIPAM) hydrogel were studied using Fourier transform infra-red (FT-IR), Field Emission Scanning Electron Microscopy (FESEM) and swelling test by weight ratio of the hydrogel. This study found that additional feed of MAA and NIPAM monomers during polymerization increased the amount of PMAA and PNIPAM crosslinked in the hydrogel. As a result, the value of LCST increased from 32℃ to more than 37℃. The swelling ratio of the hydrogel was found to be maximum at pH 7 which is suitable to be used in body system especially in human blood of pH 7.4. Thus, the role of Chitosan-P(MAA-co-NIPAM) as a carrier of a drug in drug delivery system has been approved

Design and synthesis of new thiazolidinone/uracil derivatives as antiproliferative agents targeting EGFR and/or BRAFV600E^{V600E}

Thiourea derivatives of uracil were efficiently synthesized via the reaction of 5-aminouracil with isothiocyanates. Then, we prepared uracil-containing thiazoles via condensation of thioureas with diethyl/dimethyl acetylenedicarboxylates. The structures of the products were confirmed by a combination of spectral techniques including infra-red (IR), nuclear magnetic resonance (NMR), mass spectrometry (MS) and elemental analyses. A rationale for the formation of the products is presented. The newly synthesized compounds were evaluated for their in vitro antiproliferative activity against four cancer cell lines. The compounds tested showed promising antiproliferative activity, with GI$_{50}$ values ranging from 1.10 µM to 10.00 µM. Compounds 3c, 5b, 5c, 5h, 5i, and 5j were the most potent derivatives, with GI$_{50}$ values ranging from 1.10 µM to 1.80 µM. Compound 5b showed potent inhibitory activity against EGFR and BRAF$^{V600E}$ with IC$_{50}$ of 91 ± 07 and 93 ± 08 nM, respectively, indicating that this compound could serve as a dual inhibitor of EGFR and BRAF$^{V600E}$ with promising antiproliferative properties. Docking computations revealed the great potency of compounds 5b and 5j towards EGFR and BRAF$^{V600E}$ with docking scores of −8.3 and −9.7 kcal/mol and −8.2 and −9.3 kcal/mol, respectively

The Neuroscience Information Framework: A Data and Knowledge Environment for Neuroscience

With support from the Institutes and Centers forming the NIH Blueprint for Neuroscience Research, we have designed and implemented a new initiative for integrating access to and use of Web-based neuroscience resources: the Neuroscience Information Framework. The Framework arises from the expressed need of the neuroscience community for neuroinformatic tools and resources to aid scientific inquiry, builds upon prior development of neuroinformatics by the Human Brain Project and others, and directly derives from the Society for Neuroscience’s Neuroscience Database Gateway. Partnered with the Society, its Neuroinformatics Committee, and volunteer consultant-collaborators, our multi-site consortium has developed: (1) a comprehensive, dynamic, inventory of Web-accessible neuroscience resources, (2) an extended and integrated terminology describing resources and contents, and (3) a framework accepting and aiding concept-based queries. Evolving instantiations of the Framework may be viewed at http://nif.nih.gov, http://neurogateway.org, and other sites as they come on line

Tackling the Mouse‐on‐Mouse Problem in Cochlear Immunofluorescence: A Simple Double‐Blocking Protocol for Immunofluorescent Labeling of Murine Cochlear Sections with Primary Mouse Antibodies

The mouse is the most widely used animal model in hearing research. Immunohistochemistry and immunofluorescent staining of murine cochlear sections have, thus, remained a backbone of inner ear research. Since many primary antibodies are raised in mouse, the problem of "mouse-on-mouse" background arises due to the interaction between the anti-mouse secondary antibody and the native mouse immunoglobulins. Here, we describe the pattern of mouse-on-mouse background fluorescence in sections of the postnatal mouse cochlea. Furthermore, we describe a simple double-blocking immunofluorescence protocol to label mouse cochlear cryosections. The protocol contains a conventional blocking step with serum, and an additional blocking step with a commercially available anti-mouse IgG blocking reagent. This blocking technique virtually eliminates the "mouse-on-mouse" background in murine cochlear sections, while adding only a little time to the staining protocol. We provide detailed instructions and practical tips for tissue harvesting, processing, and immunofluorescence-labeling. Further protocol modifications are described, to shorten the duration of the protocol, based on the primary antibody incubation temperature. Finally, we demonstrate examples of immunofluorescence staining performed using different incubation times and various incubation temperatures with a commercially available mouse monoclonal primary antibody

A hybrid human and machine resource curation pipeline for the Neuroscience Information Framework

The breadth of information resources available to researchers on the Internet continues to expand, particularly in light of recently implemented data-sharing policies required by funding agencies. However, the nature of dense, multifaceted neuroscience data and the design of contemporary search engine systems makes efficient, reliable and relevant discovery of such information a significant challenge. This challenge is specifically pertinent for online databases, whose dynamic content is ‘hidden’ from search engines. The Neuroscience Information Framework (NIF; http://www.neuinfo.org) was funded by the NIH Blueprint for Neuroscience Research to address the problem of finding and utilizing neuroscience-relevant resources such as software tools, data sets, experimental animals and antibodies across the Internet. From the outset, NIF sought to provide an accounting of available resources, whereas developing technical solutions to finding, accessing and utilizing them. The curators therefore, are tasked with identifying and registering resources, examining data, writing configuration files to index and display data and keeping the contents current. In the initial phases of the project, all aspects of the registration and curation processes were manual. However, as the number of resources grew, manual curation became impractical. This report describes our experiences and successes with developing automated resource discovery and semiautomated type characterization with text-mining scripts that facilitate curation team efforts to discover, integrate and display new content. We also describe the DISCO framework, a suite of automated web services that significantly reduce manual curation efforts to periodically check for resource updates. Lastly, we discuss DOMEO, a semi-automated annotation tool that improves the discovery and curation of resources that are not necessarily website-based (i.e. reagents, software tools). Although the ultimate goal of automation was to reduce the workload of the curators, it has resulted in valuable analytic by-products that address accessibility, use and citation of resources that can now be shared with resource owners and the larger scientific community

The future of psychiatric research: Genomes and neural circuits

The burden of neuropsychiatric illnesses is enormous. These conditions, which include schizophrenia, mood disorders, and autism, affect thought, emotions, and a person's very sense of self. Together, they are the leading cause of disability in North America and Europe and constitute 40% of all years lost to disability. In the United States, the cost in lost earnings due to psychiatric disease is estimated conservatively to be $200 billion per year (1). The burden to individuals, families, and society is all the more tragic because these illnesses typically begin early in life, are life-long, and damage the affected individuals' self-perception, productivity, and ability to relate to others