Thin Film Ceramic Strain Sensor Development for High Temperature Environments

The need for sensors to operate in harsh environments is illustrated by the need for measurements in the turbine engine hot section. The degradation and damage that develops over time in hot section components can lead to catastrophic failure. At present, the degradation processes that occur in the harsh hot section environment are poorly characterized, which hinders development of more durable components, and since it is so difficult to model turbine blade temperatures, strains, etc, actual measurements are needed. The need to consider ceramic sensing elements is brought about by the temperature limits of metal thin film sensors in harsh environments. The effort at the NASA Glenn Research Center (GRC) to develop high temperature thin film ceramic static strain gauges for application in turbine engines is described, first in the fan and compressor modules, and then in the hot section. The near-term goal of this research effort was to identify candidate thin film ceramic sensor materials and provide a list of possible thin film ceramic sensor materials and corresponding properties to test for viability. A thorough literature search was conducted for ceramics that have the potential for application as high temperature thin film strain gauges chemically and physically compatible with the NASA GRCs microfabrication procedures and substrate materials. Test results are given for tantalum, titanium and zirconium-based nitride and oxynitride ceramic films

Activated CD4+ T cells enhance radiation effect through the cooperation of interferon-γ and TNF-α

<p>Abstract</p> <p>Background</p> <p>Approaches that enhance radiation effect may lead to improved clinical outcome and decrease toxicity. Here we investigated whether activated CD4+ T cells (aCD4) can serve as an effective radiosensitizer.</p> <p>Methods</p> <p>CD4+ T cells were activated with anti-CD3 and anti-CD28 mAbs. Hela cells were presensitized with aCD4 or conditioned supernatant (aCD4S) or recombinant cytokines for 2 days, followed γ-irradiation. The treated cells were cultured for an additional 2 to 5 days for cell proliferation, cell cycle, and western blot assays. For confirmation, other cancer cell lines were also used.</p> <p>Results</p> <p>Presensitization of tumor cells with aCD4 greatly increased tumor cell growth inhibition. Soluble factors secreted from activated CD4⁺T cells were primarily responsible for the observed effect. IFN-γ seemed to play a major role. TNF-α, though inactive by itself, significantly augmented the radiosensitizing activity of IFN-γ. aCD4S, but not IFN-γ or IFN-γ/TNF-α combination, was found to enhance the γ-irradiation-induced G2/M phase arrest. Bax expression was highly upregulated in Hela cells presensitized with aCD4S followed by γ-irradiation. The radio-sensitizing activity of aCD4 is not uniquely observed with Hela cell line, but also seen with other cancer cell lines of various histology.</p> <p>Conclusions</p> <p>Our findings suggest possible molecular and cellular mechanisms that may help explain the radio-sensitization effect of activated lymphocytes, and may provide an improved strategy in the treatment of cancer with radiotherapy.</p

FDA Critical Path Initiatives: Opportunities for Generic Drug Development

FDA’s critical path initiative documents have focused on the challenges involved in the development of new drugs. Some of the focus areas identified apply equally to the production of generic drugs. However, there are scientific challenges unique to the development of generic drugs as well. In May 2007, FDA released a document “Critical Path Opportunities for Generic Drugs” that identified some of the specific challenges in the development of generic drugs. The key steps in generic product development are usually characterization of the reference product, design of a pharmaceutically equivalent and bioequivalent product, design of a consistent manufacturing process and conduct of the pivotal bioequivalence study. There are several areas of opportunity where scientific progress could accelerate the development and approval of generic products and expand the range of products for which generic versions are available, while maintaining high standards for quality, safety, and efficacy. These areas include the use of quality by design to develop bioequivalent products, more efficient bioequivalence methods for systemically acting drugs (expansion of BCS waivers, highly variable drugs), and development of new bioequivalence methods for locally acting drugs

Essential versus accessory aspects of cell death: recommendations of the NCCD 2015

Cells exposed to extreme physicochemical or mechanical stimuli die in an uncontrollable manner, as a result of their immediate structural breakdown. Such an unavoidable variant of cellular demise is generally referred to as ‘accidental cell death’ (ACD). In most settings, however, cell death is initiated by a genetically encoded apparatus, correlating with the fact that its course can be altered by pharmacologic or genetic interventions. ‘Regulated cell death’ (RCD) can occur as part of physiologic programs or can be activated once adaptive responses to perturbations of the extracellular or intracellular microenvironment fail. The biochemical phenomena that accompany RCD may be harnessed to classify it into a few subtypes, which often (but not always) exhibit stereotyped morphologic features. Nonetheless, efficiently inhibiting the processes that are commonly thought to cause RCD, such as the activation of executioner caspases in the course of apoptosis, does not exert true cytoprotective effects in the mammalian system, but simply alters the kinetics of cellular demise as it shifts its morphologic and biochemical correlates. Conversely, bona fide cytoprotection can be achieved by inhibiting the transduction of lethal signals in the early phases of the process, when adaptive responses are still operational. Thus, the mechanisms that truly execute RCD may be less understood, less inhibitable and perhaps more homogeneous than previously thought. Here, the Nomenclature Committee on Cell Death formulates a set of recommendations to help scientists and researchers to discriminate between essential and accessory aspects of cell death

Perceived dental treatment need among older Tanzanian adults – a cross-sectional study

Need perceptions for dental care play a key role as to whether people in general will seek dental care. The aim was to assess the prevalence of perceived need of problem based dental care, dental check-ups and any type of dental care. Guided by the conceptual model of Wilson and Cleary, the relationship of perceived need for dental care with socio-demographic characteristics, clinically defined dental problems and self-reported oral health outcomes was investigated. Partial prosthetic treatment need was estimated using a socio-dental approach. A cross-sectional survey was conducted in Pwani region and in Dar es Salaam in 2004/2005. Information from interviews and clinical examination became available for 511 urban and 520 rural adults (mean age 62.9 yr). 51.7% (95% CI 46.2, 57.0) urban and 62.5 % (95% CI 53.1, 70.9) rural inhabitants confirmed need for dental check-up, 42.9% (95% CI 36.9, 48.9) urban and 52.7% (95% CI 44.5, 60.6) rural subjects confirmed need for problem oriented care and 38.4% (95% CI 32.4, 44.6) urban versus 49.6% (95% CI 41.8, 57.4) rural residents reported need for any type of dental care. Binary and ordinal multiple logistic regression analyses revealed that adults who reported bad oral health and broken teeth were more likely to perceive need for dental care across the three outcome measures than their counterparts. Socio-demographic factors and clinically defined problems had less impact. Based on a normative and an integrated socio-dental approach respectively 39.5% and 4.7% were in need for partial dentures. About half of the participants confirmed need for problem oriented care, dental check-ups and any type of dental care. Need perceptions were influenced by perceived oral health, clinically assessed oral problems and socio-demographic characteristics. Need estimates for partial denture was higher when based on clinical examination alone compared to an integrative socio-dental approach

Immunologic and pathologic characterization of a novel swine biomedical research model for eosinophilic esophagitis

Eosinophilic esophagitis (EoE) is a chronic allergy-mediated condition with an increasing incidence in both children and adults. Despite EoE's strong impact on human health and welfare, there is a large unmet need for treatments with only one recently FDA-approved medication for EoE. The goal of this study was to establish swine as a relevant large animal model for translational biomedical research in EoE with the potential to facilitate development of therapeutics. We recently showed that after intraperitoneal sensitization and oral challenge with the food allergen hen egg white protein (HEWP), swine develop esophageal eosinophilia—a hallmark of human EoE. Herein, we used a similar sensitization and challenge treatment and evaluated immunological and pathological markers associated with human EoE. Our data demonstrate that the incorporated sensitization and challenge treatment induces (i) a systemic T-helper 2 and IgE response, (ii) a local expression of eotaxin-1 and other allergy-related immune markers, (iii) esophageal eosinophilia (>15 eosinophils/0.24 mm2), and (iv) esophageal endoscopic findings including linear furrows and white exudates. Thereby, we demonstrate that our sensitization and oral challenge protocol not only induces the underlying immune markers but also the micro- and macro-pathological hallmarks of human EoE. This swine model for EoE represents a novel relevant large animal model that can drive translational biomedical research to develop urgently needed treatment strategies for EoE

Evidence for Nearby Supernova Explosions

Supernova explosions are one of the most energetic--and potentially lethal--phenomena in the Universe. Scientists have speculated for decades about the possible consequences for life on Earth of a nearby supernova, but plausible candidates for such an event were lacking. Here we show that the Scorpius-Centaurus OB association, a group of young stars currently located at~130 parsecs from the Sun, has generated 20 SN explosions during the last 11 Myr, some of them probably as close as 40 pc to our planet. We find that the deposition on Earth of 60Fe atoms produced by these explosions can explain the recent measurements of an excess of this isotope in deep ocean crust samples. We propose that ~2 Myr ago, one of the SNe exploded close enough to Earth to seriously damage the ozone layer, provoking or contributing to the Pliocene-Pleistocene boundary marine extinction.Comment: 4 pages, 2 figures. Replaced by final version to appear in Physical Review Letter

Histological and immunohistochemical features suggesting aetiological differences in lymph node and (muco)cutaneous feline tuberculosis lesions

Objectives To identify and describe histological and immunohistochemical criteria that may differentiate between skin and lymph node lesions associated with Mycobacterium (M.) bovis and M. microti in a diagnostic pathology setting.Materials and Methods&lt;jats:p/&gt;Archived skin and lymph node biopsies of tuberculous lesions were stained with haematoxylin and eosin, Ziehl‐Neelsen and Masson's Trichrome. Immunohistochemistry was performed to detect the expression of calprotectin, CD3 and Pax5. Samples were scored for histological parameters (i.e. granulomas with central necrosis versus small granulomas without central necrosis, percentage necrosis and/or multinucleated giant cells), number of acid‐fast bacilli (bacterial index) and lesion percentage of fibrosis and positive immunohistochemical staining.Results Twenty‐two samples were examined (M. bovis n=11, M. microti n=11). When controlling for age, gender and tissue, feline M. bovis‐associated lesions more often featured large multi‐layered granulomas with central necrosis. Conversely, this presentation was infrequent in feline M. microti‐associated lesions, where small granulomas without central necrosis predominated. The presence of an outer fibrous capsule was variable in both groups, as was the bacterial index. There were no differences in intralesional expression of immunohistochemical markers.Clinical Significance Differences in the histological appearance of skin and lymph node lesions may help to infer feline infection with either M. bovis or M. microti at an earlier stage when investigating these cases, informing clinicians of the potential zoonotic risk. Importantly, cases of tuberculosis can present with numerous acid‐fast bacilli. This implies that a high bacterial index does not infer infection with non‐zoonotic non‐tuberculous mycobacteria

Primary intestinal lymphangiectasia (Waldmann's disease)

Primary intestinal lymphangiectasia (PIL) is a rare disorder characterized by dilated intestinal lacteals resulting in lymph leakage into the small bowel lumen and responsible for protein-losing enteropathy leading to lymphopenia, hypoalbuminemia and hypogammaglobulinemia. PIL is generally diagnosed before 3 years of age but may be diagnosed in older patients. Prevalence is unknown. The main symptom is predominantly bilateral lower limb edema. Edema may be moderate to severe with anasarca and includes pleural effusion, pericarditis or chylous ascites. Fatigue, abdominal pain, weight loss, inability to gain weight, moderate diarrhea or fat-soluble vitamin deficiencies due to malabsorption may also be present. In some patients, limb lymphedema is associated with PIL and is difficult to distinguish lymphedema from edema. Exsudative enteropathy is confirmed by the elevated 24-h stool α1-antitrypsin clearance. Etiology remains unknown. Very rare familial cases of PIL have been reported. Diagnosis is confirmed by endoscopic observation of intestinal lymphangiectasia with the corresponding histology of intestinal biopsy specimens. Videocapsule endoscopy may be useful when endoscopic findings are not contributive. Differential diagnosis includes constrictive pericarditis, intestinal lymphoma, Whipple's disease, Crohn's disease, intestinal tuberculosis, sarcoidosis or systemic sclerosis. Several B-cell lymphomas confined to the gastrointestinal tract (stomach, jejunum, midgut, ileum) or with extra-intestinal localizations were reported in PIL patients. A low-fat diet associated with medium-chain triglyceride supplementation is the cornerstone of PIL medical management. The absence of fat in the diet prevents chyle engorgement of the intestinal lymphatic vessels thereby preventing their rupture with its ensuing lymph loss. Medium-chain triglycerides are absorbed directly into the portal venous circulation and avoid lacteal overloading. Other inconsistently effective treatments have been proposed for PIL patients, such as antiplasmin, octreotide or corticosteroids. Surgical small-bowel resection is useful in the rare cases with segmental and localized intestinal lymphangiectasia. The need for dietary control appears to be permanent, because clinical and biochemical findings reappear after low-fat diet withdrawal. PIL outcome may be severe even life-threatening when malignant complications or serous effusion(s) occur