Monoclonal Antibody Shows Promise as Potential Therapeutic for MERS | Poster

Cancer.gov

A monoclonal antibody has proven effective in preventing Middle Eastern Respiratory Syndrome (MERS) in lab animals, suggesting further development as a potential intervention for the deadly disease in humans, according to new research. MERS is a newly emerged coronavirus first detected in humans in 2012. Most cases have occurred in the Middle East, but the disease has appeared elsewhere. In all, MERS has infected more than 1,700 individuals and killed more than 600, according to the World Health Organization. No vaccines or antiviral therapies currently exist. Several candidate vaccines are being developed, and some have been tested in animal models, a prerequisite to human clinical trials.

Characteristics of human infection with avian influenza viruses and development of new antiviral agents

PubMed Central

Liu, Qiang; Liu, Dong-ying; Yang, Zhan-qiu

2013-01-01

Since 1997, several epizootic avian influenza viruses (AIVs) have been transmitted to humans, causing diseases and even deaths. The recent emergence of severe human infections with AIV (H7N9) in China has raised concerns about efficient interpersonal viral transmission, polygenic traits in viral pathogenicity and the management of newly emerging strains. The symptoms associated with viral infection are different in various AI strains: H5N1 and newly emerged H7N9 induce severe pneumonia and related complications in patients, while some H7 and H9 subtypes cause only conjunctivitis or mild respiratory symptoms. The virulence and tissue tropism of viruses as well as the host responses contribute to the pathogenesis of human AIV infection. Several preventive and therapeutic approaches have been proposed to combat AIV infection, including antiviral drugs such as M2 inhibitors, neuraminidase inhibitors, RNA polymerase inhibitors, attachment inhibitors and signal-transduction inhibitors etc. In this article, we summarize the recent progress in researches on the epidemiology, clinical features, pathogenicity determinants, and available or potential antivirals of AIV. PMID:24096642

Determination of a risk management primer at petroleum-contaminated sites: developing new human health risk assessment strategy.

PubMed

Park, In-Sun; Park, Jae-Woo

2011-01-30

Total petroleum hydrocarbon (TPH) is an important environmental contaminant that is toxic to human and environmental receptors. However, human health risk assessment for petroleum, oil, and lubricant (POL)-contaminated sites is especially challenging because TPH is not a single compound, but rather a mixture of numerous substances. To address this concern, this study recommends a new human health risk assessment strategy for POL-contaminated sites. The strategy is based on a newly modified TPH fractionation method and includes an improved analytical protocol. The proposed TPH fractionation method is composed of ten fractions (e.g., aliphatic and aromatic EC8-10, EC10-12, EC12-16, EC16-22 and EC22-40). Physicochemical properties and toxicity values of each fraction were newly defined in this study. The stepwise ultrasonication-based analytical process was established to measure TPH fractions. Analytical results were compared with those from the TPH Criteria Working Group (TPHCWG) Direct Method. Better analytical efficiencies in TPH, aliphatic, and aromatic fractions were achieved when contaminated soil samples were analyzed with the new analytical protocol. Finally, a human health risk assessment was performed based on the developed tiered risk assessment framework. Results showed that a detailed quantitative risk assessment should be conducted to determine scientifically and economically appropriate cleanup target levels, although the phase II process is useful for determining the potency of human health risks posed by POL-contamination. Copyright © 2010 Elsevier B.V. All rights reserved.

Human Monoclonal Islet Cell Antibodies From a Patient with Insulin- Dependent Diabetes Mellitus Reveal Glutamate Decarboxylase as the Target Antigen

NASA Astrophysics Data System (ADS)

Richter, Wiltrud; Endl, Josef; Eiermann, Thomas H.; Brandt, Michael; Kientsch-Engel, Rosemarie; Thivolet, Charles; Jungfer, Herbert; Scherbaum, Werner A.

1992-09-01

The autoimmune phenomena associated with destruction of the β cell in pancreatic islets and development of type 1 (insulin-dependent) diabetes mellitus (IDDM) include circulating islet cell antibodies. We have immortalized peripheral blood lymphocytes from prediabetic individuals and patients with newly diagnosed IDDM by Epstein-Barr virus transformation. IgG-positive cells were selected by anti-human IgG-coupled magnetic beads and expanded in cell culture. Supernatants were screened for cytoplasmic islet cell antibodies using the conventional indirect immunofluorescence test on cryostat sections of human pancreas. Six islet cell-specific B-cell lines, originating from a patient with newly diagnosed IDDM, could be stabilized on a monoclonal level. All six monoclonal islet cell antibodies (MICA 1-6) were of the IgG class. None of the MICA reacted with human thyroid, adrenal gland, anterior pituitary, liver, lung, stomach, and intestine tissues but all six reacted with pancreatic islets of different mammalian species and, in addition, with neurons of rat cerebellar cortex. MICA 1-6 were shown to recognize four distinct antigenic epitopes in islets. Islet cell antibody-positive diabetic sera but not normal human sera blocked the binding of the monoclonal antibodies to their target epitopes. Immunoprecipitation of 35S-labeled human islet cell extracts revealed that a protein of identical size to the enzyme glutamate decarboxylase (EC 4.1.1.15) was a target of all MICA. Furthermore, antigen immunotrapped by the MICA from brain homogenates showed glutamate decarboxylase enzyme activity. MICA 1-6 therefore reveal glutamate decarboxylase as the predominant target antigen of cytoplasmic islet cell autoantibodies in a patient with newly diagnosed IDDM.

Historical ruins of remote sensing archaeology in arid desertified environment, northwestern China

NASA Astrophysics Data System (ADS)

Hu, N. K.; Li, X.

2017-02-01

Silk Road is an important exchange channel for human communication and culture propagation between ancient China and the West during historical periods. A lot of human activities performed in Silk Road and many historical ruins leave behind to present. Archaeological ruins can play a significant role in studying and restoring the past human activities, as well as understanding regional environmental changes. There were many flourishingly human activities during different historical periods that were developed in ancient Juyan Oasis in the downstream of the Heihe River Basin. A large number of historical ruins that reflect past human activities preserved between numerous of the nebkhas and sand dunes. In this study, combined high-resolution remote sensing imageries with in situ truths investigated during the fieldwork, certain unknown ruins were identified according to the image features of historical ruins that appear in remotely sensed data, which were undiscovered during the previous field archaeological investigations and unreported in the past public literatures. Almost all of the newly discovered ruins that were identified using remote sensing images are distributed in the Lvcheng and BJ2008 surroundings. Newly findings supplement the missing gaps that were not taking into account during the previous field surveys.

Comprehending the Critical Importance of Vocational Technical Education in a Global Economy Era.

ERIC Educational Resources Information Center

Wolansky, William D.

1990-01-01

Industrialized nations have learned that vocational education is essential to developing a skilled work force. Newly industrialized countries competing in the global economy are finding that automation, multinational companies, and rapid growth are making investment in human resources through training a critical strategy. (SK)

Digestibility of new dietary fibre materials, resistant glucan and hydrogenated resistant glucan in rats and humans, and the physical effects in rats.

PubMed

Oku, Tsuneyuki; Tanabe, Kenichi; Morita, Shigeki; Hamaguchi, Norihisa; Shimura, Fumio; Nakamura, Sadako

2015-11-28

Resistant glucan (RG) and hydrogenated resistant glucan (HRG) are newly developed non-digestible carbohydrate materials that decrease lifestyle-related diseases. The bioavailability of RG and HRG was investigated by in vitro experiments using human and rat small intestinal enzymes and by in vivo experiments using rats in the present study. Oligosaccharides, which are minor components of RG and HRG, were hydrolysed slightly by small intestinal enzymes of humans and rats, and the hydrolysing activity was slightly higher in rats than in humans. The amount of glucose released from HRG was greater than that from RG. However, the high-molecular-weight carbohydrates of the main components were hardly hydrolysed. Furthermore, neither RG nor HRG inhibited disaccharidase activity. When rats were raised on a diet containing 5 % of RG, HRG, resistant maltodextrin or fructo-oligosaccharide (FOS) for 4 weeks, all rats developed loose stools and did not recover during the experiment, except for the FOS group. Body weight gain was normal in all groups and was not significantly different compared with the control group. Caecal tissue and content weights were significantly increased by feeding RG or HRG, although other organ and tissue weights were not significantly different among the groups. In conclusion, RG and HRG consist of small amounts of glucose and digestible and non-digestible oligosaccharides, and large amounts of glucose polymers, which were hardly hydrolysed by α-amylase and small intestinal enzymes. RG and HRG, which were developed newly as dietary fibre materials, had no harmful effects on the growth and development of rats.

A new worm infiltrating the human cornea: A report of three cases.

PubMed

McBurney-Lin, Shan; Khorram, David; Gee, Stephen; Hoberg, Eric P; Klassen-Fischer, Mary K; Neafie, Ronald C

2018-03-01

To characterize a new species of parasitic nematode that triggers uveitis. Three previously healthy, relatively young people each contracted a corneal stromal nematode that, upon surgical removal and examination, did not match any known nematodes. Clinical ocular findings included corneal opacification, visible corneal worms, conjunctival injection, and uveitis. The three cases presented here represent a previously undescribed parasitic infection of the cornea by an unidentified nematode. These findings may represent a previously unrecognized zoonotic infection from wildlife sources and potentially a newly documented nematode requiring description. Future clinical findings regarding this newly described nematode are needed to further develop our understanding of the disease.

Blood Pyrrole-Protein Adducts--A Biomarker of Pyrrolizidine Alkaloid-Induced Liver Injury in Humans.

PubMed

Ruan, Jianqing; Gao, Hong; Li, Na; Xue, Junyi; Chen, Jie; Ke, Changqiang; Ye, Yang; Fu, Peter Pi-Cheng; Zheng, Jiang; Wang, Jiyao; Lin, Ge

2015-01-01

Pyrrolizidine alkaloids (PAs) induce liver injury (PA-ILI) and is very likely to contribute significantly to drug-induced liver injury (DILI). In this study we used a newly developed ultra-high performance liquid chromatography-triple quadrupole-mass spectrometry (UHPLC-MS)-based method to detect and quantitate blood pyrrole-protein adducts in DILI patients. Among the 46 suspected DILI patients, 15 were identified as PA-ILI by the identification of PA-containing herbs exposed. Blood pyrrole-protein adducts were detected in all PA-ILI patients (100%). These results confirm that PA-ILI is one of the major causes of DILI and that blood pyrrole-protein adducts quantitated by the newly developed UHPLC-MS method can serve as a specific biomarker of PA-ILI.

A Graphical Operator Interface for a Telerobotic Inspection System

NASA Technical Reports Server (NTRS)

Kim, W. S.; Tso, K. S.; Hayati, S.

1993-01-01

Operator interface has recently emerged as an important element for efficient and safe operatorinteractions with the telerobotic system. Recent advances in graphical user interface (GUI) andgraphics/video merging technologies enable development of more efficient, flexible operatorinterfaces. This paper describes an advanced graphical operator interface newly developed for aremote surface inspection system at Jet Propulsion Laboratory. The interface has been designed sothat remote surface inspection can be performed by a single operator with an integrated robot controland image inspection capability. It supports three inspection strategies of teleoperated human visual inspection, human visual inspection with automated scanning, and machine-vision-based automated inspection.

Heartbeat synchronized with ventilation

NASA Astrophysics Data System (ADS)

Schäfer, Carsten; Rosenblum, Michael G.; Kurths, Jürgen; Abel, Hans-Henning

1998-03-01

It is widely accepted that cardiac and respiratory rhythms in humans are unsynchronised. However, a newly developed data analysis technique allows any interaction that does occur in even weakly coupled complex systems to be observed. Using this technique, we found long periods of hidden cardiorespiratory synchronization, lasting up to 20 minutes, during spontaneous breathing at rest.

Modelling Seasonal Brucellosis Epidemics in Bayingolin Mongol Autonomous Prefecture of Xinjiang, China, 2010–2014

PubMed Central

Lou, Pengwei; Wang, Lei; Zhang, Xueliang; Xu, Jiabo

2016-01-01

Brucellosis is one of the severe public health problems; the cumulative number of new human brucellosis cases reached 211515 from 2010 to 2014 in China. Bayingolin Mongol Autonomous Prefecture is situated in the southeast of Xinjiang, where brucellosis infection occurs every year. Based on the reported data of newly acute human brucellosis cases for each season in Bayingolin Mongol Autonomous Prefecture, we proposed a susceptible, exposed, infected, and vaccinated (SEIV) model with periodic transmission rates to investigate the seasonal brucellosis transmission dynamics among sheep/cattle and from sheep/cattle to humans. Compared with the criteria of MAPE and RMSPE, the model simulations agree to the data on newly acute human brucellosis. We predict that the number of newly acute human brucellosis is increasing and will peak 15325 [95% CI: 11920–18242] around the summer of 2023. We also estimate the basic reproduction number R 0 = 2.5524 [95% CI: 2.5129–2.6225] and perform some sensitivity analysis of the newly acute human brucellosis cases and the basic reproduction number R 0 in terms of model parameters. Our study demonstrates that reducing the birth number of sheep/cattle, raising the slaughter rate of infected sheep/cattle, increasing the vaccination rate of susceptible sheep/cattle, and decreasing the loss rate of vaccination are effective strategies to control brucellosis epidemic. PMID:27872852

Big earth-observation data analytics for modelling pan-tropical land-use change trajectories for newly deforested areas

NASA Astrophysics Data System (ADS)

Coca Castro, Alejandro; Reymondin, Louis; Rebetez, Julien; Fabio Satizabal Mejia, Hector; Perez-Uribe, Andres; Mulligan, Mark; Smith, Thomas; Hyman, Glenn

2017-04-01

Global land use monitoring is important to the the Sustainable Development Goals (SDGs). The latest advances in storage and manipulation of big earth-observation data have been key to developing multiple operational forest monitoring initiatives such as FORMA, Terra-i and Global Forest Change. Although the data provided by these systems are useful for identifying and estimating newly deforested areas (from 2000), they do not provide details about the land use to which these deforested areas are transitioned. This information is critical to understand the biodiversity and ecosystem services impact of deforestation and the resulting impacts on human wellbeing, locally and downstream. With the aim of contributing to current forest monitoring initiatives, this research presents a set of experimental case studies in Latin America which integrate existing land-change information derived from remote sensing image and aerial photography/ground datasets, high-temporal resolution MODIS data, advanced machine learning (i.e deep learning) and big data technologies (i.e. Hadoop and Spark) to assess land-use change trajectories in newly deforested areas in near real time.

In Silico Prediction and Experimental Confirmation of HA Residues Conferring Enhanced Human Receptor Specificity of H5N1 Influenza A Viruses.

PubMed

Schmier, Sonja; Mostafa, Ahmed; Haarmann, Thomas; Bannert, Norbert; Ziebuhr, John; Veljkovic, Veljko; Dietrich, Ursula; Pleschka, Stephan

2015-06-19

Newly emerging influenza A viruses (IAV) pose a major threat to human health by causing seasonal epidemics and/or pandemics, the latter often facilitated by the lack of pre-existing immunity in the general population. Early recognition of candidate pandemic influenza viruses (CPIV) is of crucial importance for restricting virus transmission and developing appropriate therapeutic and prophylactic strategies including effective vaccines. Often, the pandemic potential of newly emerging IAV is only fully recognized once the virus starts to spread efficiently causing serious disease in humans. Here, we used a novel phylogenetic algorithm based on the informational spectrum method (ISM) to identify potential CPIV by predicting mutations in the viral hemagglutinin (HA) gene that are likely to (differentially) affect critical interactions between the HA protein and target cells from bird and human origin, respectively. Predictions were subsequently validated by generating pseudotyped retrovirus particles and genetically engineered IAV containing these mutations and characterizing potential effects on virus entry and replication in cells expressing human and avian IAV receptors, respectively. Our data suggest that the ISM-based algorithm is suitable to identify CPIV among IAV strains that are circulating in animal hosts and thus may be a new tool for assessing pandemic risks associated with specific strains.

In Silico Prediction and Experimental Confirmation of HA Residues Conferring Enhanced Human Receptor Specificity of H5N1 Influenza A Viruses

NASA Astrophysics Data System (ADS)

Schmier, Sonja; Mostafa, Ahmed; Haarmann, Thomas; Bannert, Norbert; Ziebuhr, John; Veljkovic, Veljko; Dietrich, Ursula; Pleschka, Stephan

2015-06-01

Newly emerging influenza A viruses (IAV) pose a major threat to human health by causing seasonal epidemics and/or pandemics, the latter often facilitated by the lack of pre-existing immunity in the general population. Early recognition of candidate pandemic influenza viruses (CPIV) is of crucial importance for restricting virus transmission and developing appropriate therapeutic and prophylactic strategies including effective vaccines. Often, the pandemic potential of newly emerging IAV is only fully recognized once the virus starts to spread efficiently causing serious disease in humans. Here, we used a novel phylogenetic algorithm based on the informational spectrum method (ISM) to identify potential CPIV by predicting mutations in the viral hemagglutinin (HA) gene that are likely to (differentially) affect critical interactions between the HA protein and target cells from bird and human origin, respectively. Predictions were subsequently validated by generating pseudotyped retrovirus particles and genetically engineered IAV containing these mutations and characterizing potential effects on virus entry and replication in cells expressing human and avian IAV receptors, respectively. Our data suggest that the ISM-based algorithm is suitable to identify CPIV among IAV strains that are circulating in animal hosts and thus may be a new tool for assessing pandemic risks associated with specific strains.

Cloning of a newly identified heart-specific troponin I isoform, which lacks the troponin T binding portion, using the yeast hybrid system.

PubMed

Suzuki, Hideaki; Arakawa, Yasuhiro; Ito, Masaki; Yamada, Hisashi; Horiguchi-Yamada, Junko

2006-01-01

To elucidate the molecular pathogenesis behind increased levels of laminin in cardiac muscle cells in cardiomyopathy by using a yeast hybrid screen. The present study reports the cloning of a newly identified heart-specific troponin I isoform, which is putatively linked to laminin. Future studies will explore the functional significance of this connection. Yeast two-hybrid screen analysis was performed using MLF1-interacting protein (amino acids 1 to 318) as bait. The human heart complementary DNA library was screened by using the yeast-mating method for overnight culture. Two final positive clones from the heart library were isolated. These two clones encoded the same protein, a short isoform of human cardiac troponin I (TnI) that lacked TnI exons 5 and 6. The TnI isoform has a heart-specific expression pattern and it shares several sequence features with human cardiac TnI; however, it lacks the troponin T binding portion. The heart-specific segment of the human cardiac TnI isoform shares several sequence features with human cardiac TnI, but it lacks the troponin T binding portion. These results suggest that the heart-specific TnI isoform may be involved in cardiac development and disease.

Cloning of a newly identified heart-specific troponin I isoform, which lacks the troponin T binding portion, using the yeast hybrid system

PubMed Central

Suzuki, Hideaki; Arakawa, Yasuhiro; Ito, Masaki; Yamada, Hisashi; Horiguchi-Yamada, Junko

2006-01-01

OBJECTIVE To elucidate the molecular pathogenesis behind increased levels of laminin in cardiac muscle cells in cardiomyopathy by using a yeast hybrid screen. The present study reports the cloning of a newly identified heart-specific troponin I isoform, which is putatively linked to laminin. Future studies will explore the functional significance of this connection. METHODS Yeast two-hybrid screen analysis was performed using MLF1-interacting protein (amino acids 1 to 318) as bait. The human heart complementary DNA library was screened by using the yeast-mating method for overnight culture. RESULTS Two final positive clones from the heart library were isolated. These two clones encoded the same protein, a short isoform of human cardiac troponin I (TnI) that lacked TnI exons 5 and 6. The TnI isoform has a heart-specific expression pattern and it shares several sequence features with human cardiac TnI; however, it lacks the troponin T binding portion. CONCLUSION The heart-specific segment of the human cardiac TnI isoform shares several sequence features with human cardiac TnI, but it lacks the troponin T binding portion. These results suggest that the heart-specific TnI isoform may be involved in cardiac development and disease. PMID:18651010

An operator interface design for a telerobotic inspection system

NASA Technical Reports Server (NTRS)

Kim, Won S.; Tso, Kam S.; Hayati, Samad

1993-01-01

The operator interface has recently emerged as an important element for efficient and safe interactions between human operators and telerobotics. Advances in graphical user interface and graphics technologies enable us to produce very efficient operator interface designs. This paper describes an efficient graphical operator interface design newly developed for remote surface inspection at NASA-JPL. The interface, designed so that remote surface inspection can be performed by a single operator with an integrated robot control and image inspection capability, supports three inspection strategies of teleoperated human visual inspection, human visual inspection with automated scanning, and machine-vision-based automated inspection.

Development of a one-step RT-PCR assay for detection of pancoronaviruses (α-, β-, γ-, and δ-coronaviruses) using newly designed degenerate primers for porcine and avian `fecal samples.

PubMed

Hu, Hui; Jung, Kwonil; Wang, Qiuhong; Saif, Linda J; Vlasova, Anastasia N

2018-06-01

Coronaviruses (CoVs) are critical human and animal pathogens because of their potential to cause severe epidemics of respiratory or enteric diseases. In pigs, the newly emerged porcine deltacoronavirus (PDCoV) and re-emerged porcine epidemic diarrhea virus (PEDV) reported in the US and Asia, as well as the discovery of novel CoVs in wild bats or birds, has necessitated development of improved detection and control measures for these CoVs. Because the previous pancoronavirus (panCoV) RT-PCR established in our laboratory in 2007-2011 did not detect deltacoronaviruses (δ-CoVs) in swine fecal and serum samples, our goal was to develop a new panCoV RT-PCR assay to detect known human and animal CoVs, including δ-CoVs. In this study, we designed a new primer set to amplify a 668 bp-region within the RNA-dependent RNA polymerase (RdRP) gene that encodes the most conserved protein domain of α-, β-, γ-, and δ-CoVs. We established a one-step panCoV RT-PCR assay and standardized the assay conditions. The newly established panCoV RT-PCR assay was demonstrated to have a high sensitivity and specificity. Using a panel of 60 swine biological samples (feces, intestinal contents, and sera) characterized by PEDV, PDCoV and transmissible gastroenteritis virus-specific RT-PCR assays, we demonstrated that sensitivity and specificity of the newly established panCoV RT-PCR assay were 100%. 400 avian fecal (RNA) samples were further tested simultaneously for CoV by the new panCoV RT-PCR and a one-step RT-PCR assay with the δ-CoV nucleocapsid-specific universal primers. Four of 400 avian samples were positive for CoV, three of which were positive for δ-CoV by the conventional RT-PCR. PanCoV RT-PCR fragments for 3 of the 4 CoVs were sequenced. Phylogenetic analysis revealed the presence of one γ-CoV and two δ-CoV in the sequenced samples. The newly designed panCoV RT-PCR assay should be useful for the detection of currently known CoVs in animal biological samples. Copyright © 2018 Elsevier B.V. All rights reserved.

How behavioral economics can help to avoid 'The last mile problem' in whole genome sequencing.

PubMed

Blumenthal-Barby, Jennifer S; McGuire, Amy L; Green, Robert C; Ubel, Peter A

2015-01-01

Failure to consider lessons from behavioral economics in the case of whole genome sequencing may cause us to run into the 'last mile problem' - the failure to integrate newly developed technology, on which billions of dollars have been invested, into society in a way that improves human behavior and decision-making.

10th Annual Dr. Wernher von Braun Memorial Symposium

NASA Image and Video Library

2017-10-26

Acting NASA Administrator Robert Lightfoot, in his luncheon speech at the symposium Oct. 26, spoke about the newly reestablished National Space Council chaired by Vice President Mike Pence and NASA’s directive to develop a plan for an innovative and sustainable program of exploration with commercial and international partners to enable human expansion across the solar system

Dress Codes Blues: An Exploration of Urban Students' Reactions to a Public High School Uniform Policy

ERIC Educational Resources Information Center

DaCosta, Kneia

2006-01-01

This qualitative investigation explores the responses of 22 U.S. urban public high school students when confronted with their newly imposed school uniform policy. Specifically, the study assessed students' appraisals of the policy along with compliance and academic performance. Guided by ecological human development perspectives and grounded in…

Towards Organs on Demand: Breakthroughs and Challenges in Models of Organogenesis.

PubMed

Francipane, Maria Giovanna; Lagasse, Eric

2016-09-01

In recent years, functional three-dimensional (3D) tissue generation in vitro has been significantly advanced by tissue-engineering methods, achieving better reproduction of complex native organs compared to conventional culture systems. This review will discuss traditional 3D cell culture techniques as well as newly developed technology platforms. These recent techniques provide new possibilities in the creation of human body parts and provide more accurate predictions of tissue response to drug and chemical challenges. Given the rapid advancement in the human induced pluripotent stem cell (iPSC) field, these platforms also hold great promise in the development of patient-specific, transplantable tissues and organs on demand.

Vector-based genetically modified vaccines: Exploiting Jenner's legacy.

PubMed

Ramezanpour, Bahar; Haan, Ingrid; Osterhaus, Ab; Claassen, Eric

2016-12-07

The global vaccine market is diverse while facing a plethora of novel developments. Genetic modification (GM) techniques facilitate the design of 'smarter' vaccines. For many of the major infectious diseases of humans, like AIDS and malaria, but also for most human neoplastic disorders, still no vaccines are available. It may be speculated that novel GM technologies will significantly contribute to their development. While a promising number of studies is conducted on GM vaccines and GM vaccine technologies, the contribution of GM technology to newly introduced vaccines on the market is disappointingly limited. In this study, the field of vector-based GM vaccines is explored. Data on currently available, actually applied, and newly developed vectors is retrieved from various sources, synthesised and analysed, in order to provide an overview on the use of vector-based technology in the field of GM vaccine development. While still there are only two vector-based vaccines on the human vaccine market, there is ample activity in the fields of patenting, preclinical research, and different stages of clinical research. Results of this study revealed that vector-based vaccines comprise a significant part of all GM vaccines in the pipeline. This study further highlights that poxviruses and adenoviruses are among the most prominent vectors in GM vaccine development. After the approval of the first vectored human vaccine, based on a flavivirus vector, vaccine vector technology, especially based on poxviruses and adenoviruses, holds great promise for future vaccine development. It may lead to cheaper methods for the production of safe vaccines against diseases for which no or less perfect vaccines exist today, thus catering for an unmet medical need. After the introduction of Jenner's vaccinia virus as the first vaccine more than two centuries ago, which eventually led to the recent eradication of smallpox, this and other viruses may now be the basis for constructing vectors that may help us control other major scourges of mankind. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Antifungal Activity of Amphotericin B Conjugated to Nanosized Magnetite in the Treatment of Paracoccidioidomycosis

PubMed Central

Saldanha, Camila Arruda; Garcia, Mônica Pereira; Iocca, Diego Cesar; Rebelo, Luciana Guilherme; Souza, Ana Camila Oliveira; Bocca, Anamélia Lorenzetti; Almeida Santos, Maria de Fátima Menezes; Morais, Paulo Cesar; Azevedo, Ricardo Bentes

2016-01-01

This study reports on in vitro and in vivo tests that sought to assess the antifungal activity of a newly developed magnetic carrier system comprising amphotericin B loaded onto the surface of pre-coated (with a double-layer of lauric acid) magnetite nanoparticles. The in vitro tests compared two drugs; i.e., this newly developed form and free amphotericin B. We found that this nanocomplex exhibited antifungal activity without cytotoxicity to human urinary cells and with low cytotoxicity to peritoneal macrophages. We also evaluated the efficacy of the nanocomplex in experimental paracoccidioidomycosis. BALB/c mice were intratracheally infected with Paracoccidioides brasiliensis and treated with the compound for 30 or 60 days beginning the day after infection. The newly developed amphotericin B coupled with magnetic nanoparticles was effective against experimental paracoccidioidomycosis, and it did not induce clinical, biochemical or histopathological alterations. The nanocomplex also did not induce genotoxic effects in bone marrow cells. Therefore, it is reasonable to believe that amphotericin B coupled to magnetic nanoparticles and stabilized with bilayer lauric acid is a promising nanotool for the treatment of the experimental paracoccidioidomycosis because it exhibited antifungal activity that was similar to that of free amphotericin B, did not induce adverse effects in therapeutic doses and allowed for a reduction in the number of applications. PMID:27303789

Comparative Proteomics of Human and Macaque Milk Reveals Species-Specific Nutrition during Postnatal Development.

PubMed

Beck, Kristen L; Weber, Darren; Phinney, Brett S; Smilowitz, Jennifer T; Hinde, Katie; Lönnerdal, Bo; Korf, Ian; Lemay, Danielle G

2015-05-01

Milk has been well established as the optimal nutrition source for infants, yet there is still much to be understood about its molecular composition. Therefore, our objective was to develop and compare comprehensive milk proteomes for human and rhesus macaques to highlight differences in neonatal nutrition. We developed a milk proteomics technique that overcomes previous technical barriers including pervasive post-translational modifications and limited sample volume. We identified 1606 and 518 proteins in human and macaque milk, respectively. During analysis of detected protein orthologs, we identified 88 differentially abundant proteins. Of these, 93% exhibited increased abundance in human milk relative to macaque and include lactoferrin, polymeric immunoglobulin receptor, alpha-1 antichymotrypsin, vitamin D-binding protein, and haptocorrin. Furthermore, proteins more abundant in human milk compared with macaque are associated with development of the gastrointestinal tract, the immune system, and the brain. Overall, our novel proteomics method reveals the first comprehensive macaque milk proteome and 524 newly identified human milk proteins. The differentially abundant proteins observed are consistent with the perspective that human infants, compared with nonhuman primates, are born at a slightly earlier stage of somatic development and require additional support through higher quantities of specific proteins to nurture human infant maturation.

Rational Design of Mouse Models for Cancer Research.

PubMed

Landgraf, Marietta; McGovern, Jacqui A; Friedl, Peter; Hutmacher, Dietmar W

2018-03-01

The laboratory mouse is widely considered as a valid and affordable model organism to study human disease. Attempts to improve the relevance of murine models for the investigation of human pathologies led to the development of various genetically engineered, xenograft and humanized mouse models. Nevertheless, most preclinical studies in mice suffer from insufficient predictive value when compared with cancer biology and therapy response of human patients. We propose an innovative strategy to improve the predictive power of preclinical cancer models. Combining (i) genomic, tissue engineering and regenerative medicine approaches for rational design of mouse models with (ii) rapid prototyping and computational benchmarking against human clinical data will enable fast and nonbiased validation of newly generated models. Copyright © 2017 Elsevier Ltd. All rights reserved.

Physical environment virtualization for human activities recognition

NASA Astrophysics Data System (ADS)

Poshtkar, Azin; Elangovan, Vinayak; Shirkhodaie, Amir; Chan, Alex; Hu, Shuowen

2015-05-01

Human activity recognition research relies heavily on extensive datasets to verify and validate performance of activity recognition algorithms. However, obtaining real datasets are expensive and highly time consuming. A physics-based virtual simulation can accelerate the development of context based human activity recognition algorithms and techniques by generating relevant training and testing videos simulating diverse operational scenarios. In this paper, we discuss in detail the requisite capabilities of a virtual environment to aid as a test bed for evaluating and enhancing activity recognition algorithms. To demonstrate the numerous advantages of virtual environment development, a newly developed virtual environment simulation modeling (VESM) environment is presented here to generate calibrated multisource imagery datasets suitable for development and testing of recognition algorithms for context-based human activities. The VESM environment serves as a versatile test bed to generate a vast amount of realistic data for training and testing of sensor processing algorithms. To demonstrate the effectiveness of VESM environment, we present various simulated scenarios and processed results to infer proper semantic annotations from the high fidelity imagery data for human-vehicle activity recognition under different operational contexts.

Oxytocin Receptor Gene Polymorphisms Are Associated with Human Directed Social Behavior in Dogs (Canis familiaris)

PubMed Central

Lakatos, Gabriella; Pergel, Enikő; Turcsán, Borbála; Pluijmakers, Jolanda; Vas, Judit; Elek, Zsuzsanna; Brúder, Ildikó; Földi, Levente; Sasvári-Székely, Mária; Miklósi, Ádám; Rónai, Zsolt; Kubinyi, Enikő

2014-01-01

The oxytocin system has a crucial role in human sociality; several results prove that polymorphisms of the oxytocin receptor gene are related to complex social behaviors in humans. Dogs' parallel evolution with humans and their adaptation to the human environment has made them a useful species to model human social interactions. Previous research indicates that dogs are eligible models for behavioral genetic research, as well. Based on these previous findings, our research investigated associations between human directed social behaviors and two newly described (−212AG, 19131AG) and one known (rs8679684) single nucleotide polymorphisms (SNPs) in the regulatory regions (5′ and 3′ UTR) of the oxytocin receptor gene in German Shepherd (N = 104) and Border Collie (N = 103) dogs. Dogs' behavior traits have been estimated in a newly developed test series consisting of five episodes: Greeting by a stranger, Separation from the owner, Problem solving, Threatening approach, Hiding of the owner. Buccal samples were collected and DNA was isolated using standard protocols. SNPs in the 3′ and 5′ UTR regions were analyzed by polymerase chain reaction based techniques followed by subsequent electrophoresis analysis. The gene–behavior association analysis suggests that oxytocin receptor gene polymorphisms have an impact in both breeds on (i) proximity seeking towards an unfamiliar person, as well as their owner, and on (ii) how friendly dogs behave towards strangers, although the mediating molecular regulatory mechanisms are yet unknown. Based on these results, we conclude that similarly to humans, the social behavior of dogs towards humans is influenced by the oxytocin system. PMID:24454713

Oxytocin receptor gene polymorphisms are associated with human directed social behavior in dogs (Canis familiaris).

PubMed

Kis, Anna; Bence, Melinda; Lakatos, Gabriella; Pergel, Enikő; Turcsán, Borbála; Pluijmakers, Jolanda; Vas, Judit; Elek, Zsuzsanna; Brúder, Ildikó; Földi, Levente; Sasvári-Székely, Mária; Miklósi, Adám; Rónai, Zsolt; Kubinyi, Enikő

2014-01-01

The oxytocin system has a crucial role in human sociality; several results prove that polymorphisms of the oxytocin receptor gene are related to complex social behaviors in humans. Dogs' parallel evolution with humans and their adaptation to the human environment has made them a useful species to model human social interactions. Previous research indicates that dogs are eligible models for behavioral genetic research, as well. Based on these previous findings, our research investigated associations between human directed social behaviors and two newly described (-212AG, 19131AG) and one known (rs8679684) single nucleotide polymorphisms (SNPs) in the regulatory regions (5' and 3' UTR) of the oxytocin receptor gene in German Shepherd (N = 104) and Border Collie (N = 103) dogs. Dogs' behavior traits have been estimated in a newly developed test series consisting of five episodes: Greeting by a stranger, Separation from the owner, Problem solving, Threatening approach, Hiding of the owner. Buccal samples were collected and DNA was isolated using standard protocols. SNPs in the 3' and 5' UTR regions were analyzed by polymerase chain reaction based techniques followed by subsequent electrophoresis analysis. The gene-behavior association analysis suggests that oxytocin receptor gene polymorphisms have an impact in both breeds on (i) proximity seeking towards an unfamiliar person, as well as their owner, and on (ii) how friendly dogs behave towards strangers, although the mediating molecular regulatory mechanisms are yet unknown. Based on these results, we conclude that similarly to humans, the social behavior of dogs towards humans is influenced by the oxytocin system.

Applicability of integrated cell culture reverse transcriptase quantitative PCR (ICC-RTqPCR) for the simultaneous detection of the four human enteric enterovirus species in disinfection studies

EPA Science Inventory

A newly developed integrated cell culture reverse transcriptase quantitative PCR (ICC-RTqPCR) method and its applicability in UV disinfection studies is described. This method utilizes a singular cell culture system coupled with four RTqPCR assays to detect infectious serotypes t...

The Clemente Program and Calgary Alberta's Storefront 101: Intuitive Connection to the Traditions and Practices of Adult Education

ERIC Educational Resources Information Center

Groen, Janet

2005-01-01

Earl Shorris launched his presentation to 20 potential applicants for his newly developed humanities course directed toward the poor and disenfranchised in New York City. Since this inaugural course in New York, the Clemente Course has been launched in numerous centres across the United States, Canada, Australia, and Mexico. The course is named…

Improving the Selection, Classification, and Utilization of Army Enlisted Personnel. Annual Report, 1985 Fiscal Year. Supplement

DTIC Science & Technology

1987-10-01

PERFORMING ORGANIZATION NAME AND ADDRESS 10. PROGRAM ELEMENT, PROJECT, TASK Human Resources Research Organization 2 P 3 QA2 79 9"INiTNUMBERS 1100...classification tests which will validly predict carefully developed measures of job performance . The project addresses the 675,000-person enlisted personnel...are to include both Army-wide job performance measures based on newly developed rating scales, and direct hands-on measures of MOS-specific task

WiFi-Based Real-Time Calibration-Free Passive Human Motion Detection.

PubMed

Gong, Liangyi; Yang, Wu; Man, Dapeng; Dong, Guozhong; Yu, Miao; Lv, Jiguang

2015-12-21

With the rapid development of WLAN technology, wireless device-free passive human detection becomes a newly-developing technique and holds more potential to worldwide and ubiquitous smart applications. Recently, indoor fine-grained device-free passive human motion detection based on the PHY layer information is rapidly developed. Previous wireless device-free passive human detection systems either rely on deploying specialized systems with dense transmitter-receiver links or elaborate off-line training process, which blocks rapid deployment and weakens system robustness. In the paper, we explore to research a novel fine-grained real-time calibration-free device-free passive human motion via physical layer information, which is independent of indoor scenarios and needs no prior-calibration and normal profile. We investigate sensitivities of amplitude and phase to human motion, and discover that phase feature is more sensitive to human motion, especially to slow human motion. Aiming at lightweight and robust device-free passive human motion detection, we develop two novel and practical schemes: short-term averaged variance ratio (SVR) and long-term averaged variance ratio (LVR). We realize system design with commercial WiFi devices and evaluate it in typical multipath-rich indoor scenarios. As demonstrated in the experiments, our approach can achieve a high detection rate and low false positive rate.

WiFi-Based Real-Time Calibration-Free Passive Human Motion Detection †

PubMed Central

Gong, Liangyi; Yang, Wu; Man, Dapeng; Dong, Guozhong; Yu, Miao; Lv, Jiguang

2015-01-01

With the rapid development of WLAN technology, wireless device-free passive human detection becomes a newly-developing technique and holds more potential to worldwide and ubiquitous smart applications. Recently, indoor fine-grained device-free passive human motion detection based on the PHY layer information is rapidly developed. Previous wireless device-free passive human detection systems either rely on deploying specialized systems with dense transmitter-receiver links or elaborate off-line training process, which blocks rapid deployment and weakens system robustness. In the paper, we explore to research a novel fine-grained real-time calibration-free device-free passive human motion via physical layer information, which is independent of indoor scenarios and needs no prior-calibration and normal profile. We investigate sensitivities of amplitude and phase to human motion, and discover that phase feature is more sensitive to human motion, especially to slow human motion. Aiming at lightweight and robust device-free passive human motion detection, we develop two novel and practical schemes: short-term averaged variance ratio (SVR) and long-term averaged variance ratio (LVR). We realize system design with commercial WiFi devices and evaluate it in typical multipath-rich indoor scenarios. As demonstrated in the experiments, our approach can achieve a high detection rate and low false positive rate. PMID:26703612

Human embryonic stem cells express a unique set of microRNAs.

PubMed

Suh, Mi-Ra; Lee, Yoontae; Kim, Jung Yeon; Kim, Soo-Kyoung; Moon, Sung-Hwan; Lee, Ji Yeon; Cha, Kwang-Yul; Chung, Hyung Min; Yoon, Hyun Soo; Moon, Shin Yong; Kim, V Narry; Kim, Kye-Seong

2004-06-15

Human embryonic stem (hES) cells are pluripotent cell lines established from the explanted inner cell mass of human blastocysts. Despite their importance for human embryology and regenerative medicine, studies on hES cells, unlike those on mouse ES (mES) cells, have been hampered by difficulties in culture and by scant knowledge concerning the regulatory mechanism. Recent evidence from plants and animals indicates small RNAs of approximately 22 nucleotides (nt), collectively named microRNAs, play important roles in developmental regulation. Here we describe 36 miRNAs (from 32 stem-loops) identified by cDNA cloning in hES cells. Importantly, most of the newly cloned miRNAs are specifically expressed in hES cells and downregulated during development into embryoid bodies (EBs), while miRNAs previously reported from other human cell types are poorly expressed in hES cells. We further show that some of the ES-specific miRNA genes are highly related to each other, organized as clusters, and transcribed as polycistronic primary transcripts. These miRNA gene families have murine homologues that have similar genomic organizations and expression patterns, suggesting that they may operate key regulatory networks conserved in mammalian pluripotent stem cells. The newly identified hES-specific miRNAs may also serve as molecular markers for the early embryonic stage and for undifferentiated hES cells.

Progress in Brucella vaccine development

PubMed Central

YANG, Xinghong; SKYBERG, Jerod A.; CAO, Ling; CLAPP, Beata; THORNBURG, Theresa; PASCUAL, David W.

2012-01-01

Brucella spp. are zoonotic, facultative intracellular pathogens, which cause animal and human disease. Animal disease results in abortion of fetuses; in humans, it manifests flu-like symptoms with an undulant fever, with osteoarthritis as a common complication of infection. Antibiotic regimens for human brucellosis patients may last several months and are not always completely effective. While there are no vaccines for humans, several licensed live Brucella vaccines are available for use in livestock. The performance of these animal vaccines is dependent upon the host species, dose, and route of immunization. Newly engineered live vaccines, lacking well-defined virulence factors, retain low residual virulence, are highly protective, and may someday replace currently used animal vaccines. These also have possible human applications. Moreover, due to their enhanced safety and efficacy in animal models, subunit vaccines for brucellosis show great promise for their application in livestock and humans. This review summarizes the progress of brucellosis vaccine development and presents an overview of candidate vaccines. PMID:23730309

Longitudinal trends and subgroup analysis in publication patterns for preclinical data of newly approved drugs.

PubMed

Köster, Ursula; Nolte, Ingo; Michel, Martin C

2016-02-01

Having observed a large variation in the number and type of original preclinical publications for newly registered drugs, we have explored whether longitudinal trends and/or factors specific for certain drugs or their manufacturers may explain such variation. Our analysis is based on 1954 articles related to 170 newly approved drugs. The number of preclinical publications per compound declined from a median of 10.5 in 1991 to 3 in 2011. A similar trend was observed for the number of in vivo studies in general, but not in the subset of in vivo studies in animal models of disease. The percentage of compounds with studies using isolated human cells or cell lines almost doubled over time from 37 to 72%. Number of publications did not exhibit major differences between compounds intended for human versus veterinary use, therapeutic areas, small molecules versus biologicals, or innovator versus follow-up compounds; however, some companies may publish fewer studies per compound than others. However, there were qualitative differences in the types of models being used depending on the therapeutic area; specifically, compounds for use in oncology very often used isolated cells and cell lines, often from human origin. We conclude that the large variation in number and type of reported preclinical data is not easily explained. We propose that pharmaceutical companies should consistently provide a comprehensive documentation of the preclinical data they generate as part of their development programs in the public domain to enable a better understanding of the drugs they intend to market.

Biohydrogen production from space crew's waste simulants using thermophilic consolidated bioprocessing.

PubMed

Wang, Jia; Bibra, Mohit; Venkateswaran, Kasthuri; Salem, David R; Rathinam, Navanietha Krishnaraj; Gadhamshetty, Venkataraman; Sani, Rajesh K

2018-05-01

Human waste simulants were for the first time converted into biohydrogen by a newly developed anaerobic microbial consortium via thermophilic consolidated bioprocessing. Four different BioH 2 -producing consortia (denoted as C1, C2, C3 and C4) were isolated, and developed using human waste simulants as substrate. The thermophilic consortium C3, which contained Thermoanaerobacterium, Caloribacterium, and Caldanaerobius species as the main constituents, showed the highest BioH 2 production (3.999 mmol/g) from human waste simulants under optimized conditions (pH 7.0 and 60 °C). The consortium C3 also produced significant amounts of BioH 2 (5.732 mmol/g and 2.186 mmol/g) using wastewater and activated sludge, respectively. The developed consortium in this study is a promising candidate for H 2 production in space applications as in situ resource utilization. Copyright © 2018 Elsevier Ltd. All rights reserved.

Chemical Probes for Visualizing Intact Animal and Human Brain Tissue.

PubMed

Lai, Hei Ming; Ng, Wai-Lung; Gentleman, Steve M; Wu, Wutian

2017-06-22

Newly developed tissue clearing techniques can be used to render intact tissues transparent. When combined with fluorescent labeling technologies and optical sectioning microscopy, this allows visualization of fine structure in three dimensions. Gene-transfection techniques have proved very useful in visualizing cellular structures in animal models, but they are not applicable to human brain tissue. Here, we discuss the characteristics of an ideal chemical fluorescent probe for use in brain and other cleared tissues, and offer a comprehensive overview of currently available chemical probes. We describe their working principles and compare their performance with the goal of simplifying probe selection for neuropathologists and stimulating probe development by chemists. We propose several approaches for the development of innovative chemical labeling methods which, when combined with tissue clearing, have the potential to revolutionize how we study the structure and function of the human brain. Copyright © 2017 Elsevier Ltd. All rights reserved.

CRIMEtoYHU: a new web tool to develop yeast-based functional assays for characterizing cancer-associated missense variants.

PubMed

Mercatanti, Alberto; Lodovichi, Samuele; Cervelli, Tiziana; Galli, Alvaro

2017-12-01

Evaluation of the functional impact of cancer-associated missense variants is more difficult than for protein-truncating mutations and consequently standard guidelines for the interpretation of sequence variants have been recently proposed. A number of algorithms and software products were developed to predict the impact of cancer-associated missense mutations on protein structure and function. Importantly, direct assessment of the variants using high-throughput functional assays using simple genetic systems can help in speeding up the functional evaluation of newly identified cancer-associated variants. We developed the web tool CRIMEtoYHU (CTY) to help geneticists in the evaluation of the functional impact of cancer-associated missense variants. Humans and the yeast Saccharomyces cerevisiae share thousands of protein-coding genes although they have diverged for a billion years. Therefore, yeast humanization can be helpful in deciphering the functional consequences of human genetic variants found in cancer and give information on the pathogenicity of missense variants. To humanize specific positions within yeast genes, human and yeast genes have to share functional homology. If a mutation in a specific residue is associated with a particular phenotype in humans, a similar substitution in the yeast counterpart may reveal its effect at the organism level. CTY simultaneously finds yeast homologous genes, identifies the corresponding variants and determines the transferability of human variants to yeast counterparts by assigning a reliability score (RS) that may be predictive for the validity of a functional assay. CTY analyzes newly identified mutations or retrieves mutations reported in the COSMIC database, provides information about the functional conservation between yeast and human and shows the mutation distribution in human genes. CTY analyzes also newly found mutations and aborts when no yeast homologue is found. Then, on the basis of the protein domain localization and functional conservation between yeast and human, the selected variants are ranked by the RS. The RS is assigned by an algorithm that computes functional data, type of mutation, chemistry of amino acid substitution and the degree of mutation transferability between human and yeast protein. Mutations giving a positive RS are highly transferable to yeast and, therefore, yeast functional assays will be more predictable. To validate the web application, we have analyzed 8078 cancer-associated variants located in 31 genes that have a yeast homologue. More than 50% of variants are transferable to yeast. Incidentally, 88% of all transferable mutations have a reliability score >0. Moreover, we analyzed by CTY 72 functionally validated missense variants located in yeast genes at positions corresponding to the human cancer-associated variants. All these variants gave a positive RS. To further validate CTY, we analyzed 3949 protein variants (with positive RS) by the predictive algorithm PROVEAN. This analysis shows that yeast-based functional assays will be more predictable for the variants with positive RS. We believe that CTY could be an important resource for the cancer research community by providing information concerning the functional impact of specific mutations, as well as for the design of functional assays useful for decision support in precision medicine. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Quantitative detection of viable helminth ova from raw wastewater, human feces, and environmental soil samples using novel PMA-qPCR methods.

PubMed

Gyawali, P; Ahmed, W; Sidhu, J P S; Nery, S V; Clements, A C; Traub, R; McCarthy, J S; Llewellyn, S; Jagals, P; Toze, S

2016-09-01

In this study, we have evaluated the efficacy of propidium monoazide quantitative polymerase chain reaction (PMA-qPCR) to differentiate between viable and non-viable Ancylostoma caninum ova. The newly developed method was validated using raw wastewater seeded with known numbers of A. caninum ova. Results of this study confirmed that PMA-qPCR has resulted in average of 88 % reduction (P < 0.05) in gene copy numbers for 50 % viable +50 % non-viable when compared with 100 % viable ova. A reduction of 100 % in gene copies was observed for 100 % non-viable ova when compared with 100 % viable ova. Similar reductions (79-80 %) in gene copies were observed for A. caninum ova-seeded raw wastewater samples (n = 18) collected from wastewater treatment plants (WWTPs) A and B. The newly developed PMA-qPCR method was applied to determine the viable ova of different helminths (A. caninum, A. duodenale, Necator americanus and Ascaris lumbricoides) in raw wastewater, human fecal and soil samples. None of the unseeded wastewater samples were positive for the above-mentioned helminths. N. americanus and A. lumbricoides ova were found in unseeded human fecal and soil samples. For the unseeded human fecal samples (1 g), an average gene copy concentration obtained from qPCR and PMA-qPCR was found to be similar (6.8 × 10(5) ± 6.4 × 10(5) and 6.3 × 10(5) ± 4.7 × 10(5)) indicating the presence of viable N. americanus ova. Among the 24 unseeded soil samples tested, only one was positive for A. lumbricoides. The mean gene copy concentration in the positively identified soil sample was 1.0 × 10(5) ± 1.5 × 10(4) (determined by qPCR) compared to 4.9 × 10(4) ± 3.7 × 10(3) (determined by PMA-qPCR). The newly developed PMA-qPCR methods were able to detect viable helminth ova from wastewater and soil samples and could be adapted for health risk assessment.

Development of a Humanized Monoclonal Antibody with Therapeutic Potential against West Nile Virus

PubMed Central

Oliphant, Theodore; Engle, Michael; Nybakken, Grant E.; Doane, Chris; Johnson, Syd; Huang, Ling; Gorlatov, Sergey; Mehlhop, Erin; Marri, Anantha; Chung, Kyung Min; Ebel, Gregory D.; Kramer, Laura D.; Fremont, Daved H.; Diamond, Michael S.

2006-01-01

Neutralization of West Nile virus (WNV) in vivo correlates with the development of an antibody response against the viral envelope (E) protein. Using random mutagenesis and yeast surface display, we defined individual contact residues of 14 newly generated mAbs against domain III of the WNV E protein. MAbs that strongly neutralized WNV localized to a surface patch on the lateral face of domain III. Convalescent antibodies from human patients who had recovered from WNV infection also detected this epitope. One mAb, E16, neutralized 10 different strains in vitro, and demonstrated therapeutic efficacy in mice, even when administered as a single dose 5 d after infection. A humanized version of E16 was generated that retained antigen specificity, avidity, and neutralizing activity. In post-exposure therapeutic trials in mice, a single dose of humanized E16 protected mice against WNV-induced mortality, and thus, may be a viable treatment option against WNV infection in humans. PMID:15852016

A Newly Developed Nested PCR Assay for the Detection of Helicobacter pylori in the Oral Cavity.

PubMed

Ismail, Hawazen; Morgan, Claire; Griffiths, Paul; Williams, John; Jenkins, Gareth

2016-01-01

To develop a new nested polymerase chain reaction (PCR) assay for identifying Helicobacter pylori DNA from dental plaque. H. pylori is one of the most common chronic bacterial pathogens in humans. The accurate detection of this organism is essential for proper patient management and for the eradication of the bacteria following treatment. Forty-nine patients (24 males and 25 females; mean age: 51; range, 19 to 94 y) were investigated for the presence of H. pylori in dental plaque by single-step PCR and nested PCR and in the stomach by single-step PCR, nested PCR, and histologic examination. The newly developed nested PCR assay identified H. pylori DNA in gastric biopsies of 18 patients who were histologically classified as H. pylori-positive and 2 additional biopsies of patients who were H. pylori-negative by histologic examination (20/49; 40.8%). Dental plaque samples collected before and after endoscopy from the 49 patients revealed that single-step PCR did not detect H. pylori but nested PCR was able to detect H. pylori DNA in 40.8% (20/49) patients. Nested PCR gave a higher detection rate (40.8%, 20/49) than that of histology (36.7%, 18/49) and single-step PCR. When nested PCR results were compared with histology results there was no significant difference between the 2 methods. Our newly developed nested PCR assay is at least as sensitive as histology and may be useful for H. pylori detection in patients unfit for endoscopic examination.

Single-cell cloning and expansion of human induced pluripotent stem cells by a microfluidic culture device.

PubMed

Matsumura, Taku; Tatsumi, Kazuya; Noda, Yuichiro; Nakanishi, Naoyuki; Okonogi, Atsuhito; Hirano, Kunio; Li, Liu; Osumi, Takashi; Tada, Takashi; Kotera, Hidetoshi

2014-10-10

The microenvironment of cells, which includes basement proteins, shear stress, and extracellular stimuli, should be taken into consideration when examining physiological cell behavior. Although microfluidic devices allow cellular responses to be analyzed with ease at the single-cell level, few have been designed to recover cells. We herein demonstrated that a newly developed microfluidic device helped to improve culture conditions and establish a clonality-validated human pluripotent stem cell line after tracing its growth at the single-cell level. The device will be a helpful tool for capturing various cell types in the human body that have not yet been established in vitro. Copyright © 2014 Elsevier Inc. All rights reserved.

Preliminary study for a newly designed silicone stent and delivery system for canine obstructive tracheal disease.

PubMed

Kim, Dae-Hyun; Choi, Chi-Bong; Chung, Wook-Hun; Lee, Sung-Ho; Lee, A-Jin; Jeong, Jae-Seung; Kim, Ho-Joong; Kim, Hwi-Yool

2012-10-01

The goal of this study was to prove the possibility of using silicone stents broadly used for human medicine in canine obstructive tracheal disease. A silicone stent anatomically designed for canine trachea was tested on 5 beagle dogs for 8 weeks. The stent was carefully inserted using a newly developed delivery device under fluoroscopic guidance. There were no technical difficulties in placing the stent during the procedure. Previously reported complications of airway stenting such as stent migration or granulation tissue formation did not occur in any of the cases. In addition, removal of the stent was as simple as inserting it, and complications were absent. The stent introduced in this study could possibly be applied to various canine obstructive tracheal diseases.

The active translation of MHCII mRNA during dendritic cells maturation supplies new molecules to the cell surface pool.

PubMed

Malanga, Donatella; Barba, Pasquale; Harris, Paul E; Maffei, Antonella; Del Pozzo, Giovanna

2007-04-01

The transition of human dendritic cells (DCs) from the immature to the mature phenotype is characterized by an increased density of MHC class II (MHCII) molecules on the plasma membrane, a key requirement of their competence as professional antigen presenting cells (APCs). MHCII molecules on the cell surface derive from newly synthesized as well as from preexisting proteins. So far, all the studies done on DCs during maturation, to establish the relative contribution of newly synthesized MHCII molecules to the cell surface pool did not produced a clear, unified scenario. We report that, in human DCs stimulated ex vivo with LPS, the changes in the RNA accumulation specific for at least two MHCII genes (HLA-DRA and HLA-DQA1) due to transcriptional upregulation, is associated with the active translation at high rate of these transcripts. Our finding reveals that, across the 24h of the maturation process in human DCs, newly synthesized MHCII proteins are supplied to the APCs cell surface pool.

Novel ITS1 Fungal Primers for Characterization of the Mycobiome

PubMed Central

Usyk, Mykhaylo; Zolnik, Christine P.; Patel, Hitesh; Levi, Michael H.

2017-01-01

ABSTRACT Studies of the human microbiome frequently omit characterization of fungal communities (the mycobiome), which limits our ability to investigate how fungal communities influence human health. The internal transcribed spacer 1 (ITS1) region of the eukaryotic ribosomal cluster has features allowing for wide taxonomic coverage and has been recognized as a suitable barcode region for species-level identification of fungal organisms. We developed custom ITS1 primer sets using iterative alignment refinement. Primer performance was evaluated using in silico testing and experimental testing of fungal cultures and human samples. Using an expanded novel reference database, SIS (18S-ITS1-5.8S), the newly designed primers showed an average in silico taxonomic coverage of 79.9% ± 7.1% compared to a coverage of 44.6% ± 13.2% using previously published primers (P = 0.05). The newly described primer sets recovered an average of 21,830 ± 225 fungal reads from fungal isolate culture samples, whereas the previously published primers had an average of 3,305 ± 1,621 reads (P = 0.03). Of note was an increase in the taxonomic coverage of the Candida genus, which went from a mean coverage of 59.5% ± 13% to 100.0% ± 0.0% (P = 0.0015) comparing the previously described primers to the new primers, respectively. The newly developed ITS1 primer sets significantly improve general taxonomic coverage of fungal communities infecting humans and increased read depth by an order of magnitude over the best-performing published primer set tested. The overall best-performing primer pair in terms of taxonomic coverage and read recovery, ITS1-30F/ITS1-217R, will aid in advancing research in the area of the human mycobiome. IMPORTANCE The mycobiome constitutes all the fungal organisms within an environment or biological niche. The fungi are eukaryotes, are extremely heterogeneous, and include yeasts and molds that colonize humans as part of the microbiome. In addition, fungi can also infect humans and cause disease. Characterization of the bacterial component of the microbiome was revolutionized by 16S rRNA gene fragment amplification, next-generation sequencing technologies, and bioinformatics pipelines. Characterization of the mycobiome has often not been included in microbiome studies because of limitations in amplification systems. This report revisited the selection of PCR primers that amplify the fungal ITS1 region. We have identified primers with superior identification of fungi present in the database. We have compared the new primer sets against those previously used in the literature and show a significant improvement in read count and taxon identification. These primers should facilitate the study of fungi in human physiology and disease states. PMID:29242834

Promotion of hair growth by newly synthesized ceramide mimetic compound.

PubMed

Park, Bu-Mahn; Bak, Soon-Sun; Shin, Kyung-Oh; Kim, Minhee; Kim, Daehwan; Jung, Sang-Hun; Jeong, Sekyoo; Sung, Young Kwan; Kim, Hyun Jung

2017-09-09

Based on the crucial roles of ceramides in skin barrier function, use of ceramides or their structural mimetic compounds, pseudoceramides, as cosmetic ingredients are getting more popular. While currently used pseudoceramides are intended to substitute the structural roles of ceramides in stratum corneum, development of bioactive pseudoceramides has been repeatedly reported. In this study, based on the potential involvement of sphingolipids in hair cycle regulation, we investigated the effects of newly synthesized pseudoceramide, bis-oleamido isopropyl alcohol (BOI), on hair growth using cultured human hair follicles and animal models. BOI treatment promoted hair growth in cultured human hair follicles ex vivo and induced earlier conversion of telogen into anagen. Although we did not find a significant enhancement of growth factor expression and follicular cell proliferation, BOI treatment resulted in an increased sphinganine and sphingosine contents as well as increased ceramides contents in cultured dermal papilla (DP) cells. Taken together, our data strongly suggest that biologically active pseudoceramide promotes hair growth by stimulating do novo synthesis of sphingolipids in DP cells. Copyright © 2017 Elsevier Inc. All rights reserved.

Natural reservoirs for homologs of hepatitis C virus

PubMed Central

Pfaender, Stephanie; Brown, Richard JP; Pietschmann, Thomas; Steinmann, Eike

2014-01-01

Hepatitis C virus is considered a major public health problem, infecting 2%–3% of the human population. Hepatitis C virus infection causes acute and chronic liver disease, including chronic hepatitis, cirrhosis and hepatocellular carcinoma. In fact, hepatitis C virus infection is the most frequent indication for liver transplantation and a vaccine is not available. Hepatitis C virus displays a narrow host species tropism, naturally infecting only humans, although chimpanzees are also susceptible to experimental infection. To date, there is no evidence for an animal reservoir of viruses closely related to hepatitis C virus which may have crossed the species barrier to cause disease in humans and resulted in the current pandemic. In fact, due to this restricted host range, a robust immunocompetent small animal model is still lacking, hampering mechanistic analysis of virus pathogenesis, immune control and prophylactic vaccine development. Recently, several studies discovered new viruses related to hepatitis C virus, belonging to the hepaci- and pegivirus genera, in small wild mammals (rodents and bats) and domesticated animals which live in close contact with humans (dogs and horses). Genetic and biological characterization of these newly discovered hepatitis C virus-like viruses infecting different mammals will contribute to our understanding of the origins of hepatitis C virus in humans and enhance our ability to study pathogenesis and immune responses using tractable animal models. In this review article, we start with an introduction on the genetic diversity of hepatitis C virus and then focus on the newly discovered viruses closely related to hepatitis C virus. Finally, we discuss possible theories about the origin of this important viral human pathogen. PMID:26038514

Tau Kinetics in Neurons and the Human Central Nervous System.

PubMed

Sato, Chihiro; Barthélemy, Nicolas R; Mawuenyega, Kwasi G; Patterson, Bruce W; Gordon, Brian A; Jockel-Balsarotti, Jennifer; Sullivan, Melissa; Crisp, Matthew J; Kasten, Tom; Kirmess, Kristopher M; Kanaan, Nicholas M; Yarasheski, Kevin E; Baker-Nigh, Alaina; Benzinger, Tammie L S; Miller, Timothy M; Karch, Celeste M; Bateman, Randall J

2018-03-21

We developed stable isotope labeling and mass spectrometry approaches to measure the kinetics of multiple isoforms and fragments of tau in the human central nervous system (CNS) and in human induced pluripotent stem cell (iPSC)-derived neurons. Newly synthesized tau is truncated and released from human neurons in 3 days. Although most tau proteins have similar turnover, 4R tau isoforms and phosphorylated forms of tau exhibit faster turnover rates, suggesting unique processing of these forms that may have independent biological activities. The half-life of tau in control human iPSC-derived neurons is 6.74 ± 0.45 days and in human CNS is 23 ± 6.4 days. In cognitively normal and Alzheimer's disease participants, the production rate of tau positively correlates with the amount of amyloid plaques, indicating a biological link between amyloid plaques and tau physiology. Copyright © 2018 Elsevier Inc. All rights reserved.

Deep Tissue Injury in Development of Pressure Ulcers: A Decrease of Inflammasome Activation and Changes in Human Skin Morphology in Response to Aging and Mechanical Load

PubMed Central

Stojadinovic, Olivera; Minkiewicz, Julia; Sawaya, Andrew; Bourne, Jonathan W.; Torzilli, Peter; de Rivero Vaccari, Juan Pablo; Dietrich, W. Dalton; Keane, Robert W.; Tomic-Canic, Marjana

2013-01-01

Molecular mechanisms leading to pressure ulcer development are scarce in spite of high mortality of patients. Development of pressure ulcers that is initially observed as deep tissue injury is multifactorial. We postulate that biomechanical forces and inflammasome activation, together with ischemia and aging, may play a role in pressure ulcer development. To test this we used a newly-developed bio-mechanical model in which ischemic young and aged human skin was subjected to a constant physiological compressive stress (load) of 300 kPa (determined by pressure plate analyses of a person in a reclining position) for 0.5–4 hours. Collagen orientation was assessed using polarized light, whereas inflammasome proteins were quantified by immunoblotting. Loaded skin showed marked changes in morphology and NLRP3 inflammasome protein expression. Sub-epidermal separations and altered orientation of collagen fibers were observed in aged skin at earlier time points. Aged skin showed significant decreases in the levels of NLRP3 inflammasome proteins. Loading did not alter NLRP3 inflammasome proteins expression in aged skin, whereas it significantly increased their levels in young skin. We conclude that aging contributes to rapid morphological changes and decrease in inflammasome proteins in response to tissue damage, suggesting that a decline in the innate inflammatory response in elderly skin could contribute to pressure ulcer pathogenesis. Observed morphological changes suggest that tissue damage upon loading may not be entirely preventable. Furthermore, newly developed model described here may be very useful in understanding the mechanisms of deep tissue injury that may lead towards development of pressure ulcers. PMID:23967056

Global modeling of withdrawal, allocation and consumptive use of surface water and groundwater resources

NASA Astrophysics Data System (ADS)

Wada, Y.; Wisser, D.; Bierkens, M. F. P.

2014-01-01

To sustain growing food demand and increasing standard of living, global water withdrawal and consumptive water use have been increasing rapidly. To analyze the human perturbation on water resources consistently over large scales, a number of macro-scale hydrological models (MHMs) have been developed in recent decades. However, few models consider the interaction between terrestrial water fluxes, and human activities and associated water use, and even fewer models distinguish water use from surface water and groundwater resources. Here, we couple a global water demand model with a global hydrological model and dynamically simulate daily water withdrawal and consumptive water use over the period 1979-2010, using two re-analysis products: ERA-Interim and MERRA. We explicitly take into account the mutual feedback between supply and demand, and implement a newly developed water allocation scheme to distinguish surface water and groundwater use. Moreover, we include a new irrigation scheme, which works dynamically with a daily surface and soil water balance, and incorporate the newly available extensive Global Reservoir and Dams data set (GRanD). Simulated surface water and groundwater withdrawals generally show good agreement with reported national and subnational statistics. The results show a consistent increase in both surface water and groundwater use worldwide, with a more rapid increase in groundwater use since the 1990s. Human impacts on terrestrial water storage (TWS) signals are evident, altering the seasonal and interannual variability. This alteration is particularly large over heavily regulated basins such as the Colorado and the Columbia, and over the major irrigated basins such as the Mississippi, the Indus, and the Ganges. Including human water use and associated reservoir operations generally improves the correlation of simulated TWS anomalies with those of the GRACE observations.

Global Modeling of Withdrawal, Allocation and Consumptive Use of Surface Water and Groundwater Resources

NASA Astrophysics Data System (ADS)

Wada, Y.; Wisser, D.; Bierkens, M. F.

2014-12-01

To sustain growing food demand and increasing standard of living, global water withdrawal and consumptive water use have been increasing rapidly. To analyze the human perturbation on water resources consistently over large scales, a number of macro-scale hydrological models (MHMs) have been developed in recent decades. However, few models consider the interaction between terrestrial water fluxes, and human activities and associated water use, and even fewer models distinguish water use from surface water and groundwater resources. Here, we couple a global water demand model with a global hydrological model and dynamically simulate daily water withdrawal and consumptive water use over the period 1979-2010, using two re-analysis products: ERA-Interim and MERRA. We explicitly take into account the mutual feedback between supply and demand, and implement a newly developed water allocation scheme to distinguish surface water and groundwater use. Moreover, we include a new irrigation scheme, which works dynamically with a daily surface and soil water balance, and incorporate the newly available extensive global reservoir data set (GRanD). Simulated surface water and groundwater withdrawals generally show good agreement with reported national and sub-national statistics. The results show a consistent increase in both surface water and groundwater use worldwide, with a more rapid increase in groundwater use since the 1990s. Human impacts on terrestrial water storage (TWS) signals are evident, altering the seasonal and inter-annual variability. This alteration is particularly large over heavily regulated basins such as the Colorado and the Columbia, and over the major irrigated basins such as the Mississippi, the Indus, and the Ganges. Including human water use and associated reservoir operations generally improves the correlation of simulated TWS anomalies with those of the GRACE observations.

Etiology of AIDS: biological and biochemical characteristics of HTLV-III.

PubMed

Markham, P D; Shaw, G M; Salahuddin, S Z; Hahn, B; Sarngadharan, M G; Gallo, R C

1985-01-01

The newly identified human HTLV-III virus, the etiologic agent for AIDS, shares many of the biological and physicochemical properties common to a family of retroviruses named human T-cell leukemia (lymphotropic) viruses, or HTLV. Because of the similarities, and because of the uniform nomenclature for human T-cell leukemia (lymphotropic) viruses adopted at the first Cold Spring Harbor Meeting on HTLV (19, 79), this newly discovered virus associated with AIDS as HTLV-III was named HTLV-III. Other investigators making independent isolations of virus have suggested naming the virus lymphadenopathy virus or LAV (3, 16), immunodeficiency associated virus or IADV (48), AIDS-related virus (41). Immunological and nucleic acid comparison has now demonstrated that these viruses are, not surprisingly, very similar to HTLV-III (55, 63, 78). In view of the wide range of disease manifestations caused by the virus, and previous discussions concerning a uniform nomenclature for human T-lymphotropic retroviruses, it would seem ill-advised to restrict the name of this virus to one clinical manifestation of one disease. The frequent isolation of HTLV-III from patients with AIDS and ARC, the detection of antibodies specific for HTLV-III in nearly all patients with these diseases and in a high proportion of individuals at risk, and finally its effect on cells in vitro, leaves little doubt that HTLV-III is causatively involved in the development of these diseases. This etiologic association is further strengthened by the detection of HTLV-III infection in many instances where a direct cause-and-effect association can be made, e.g., hemophiliacs and children with AIDS, and blood from HTLV-III infected donors and the otherwise normal recipients of this blood who subsequently develop AIDS.

Identification of striated muscle activator of Rho signaling (STARS) as a novel calmodulin target by a newly developed genome-wide screen.

PubMed

Furuya, Yusui; Denda, Miwako; Sakane, Kyohei; Ogusu, Tomoko; Takahashi, Sumio; Magari, Masaki; Kanayama, Naoki; Morishita, Ryo; Tokumitsu, Hiroshi

2016-07-01

To search for novel target(s) of the Ca(2+)-signaling transducer, calmodulin (CaM), we performed a newly developed genome-wide CaM interaction screening of 19,676 GST-fused proteins expressed in human. We identified striated muscle activator of Rho signaling (STARS) as a novel CaM target and characterized its CaM binding ability and found that the Ca(2+)/CaM complex interacted stoichiometrically with the N-terminal region (Ala13-Gln35) of STARS in vitro as well as in living cells. Mutagenesis studies identified Ile20 and Trp33 as the essential hydrophobic residues in CaM anchoring. Furthermore, the CaM binding deficient mutant (Ile20Ala, Trp33Ala) of STARS further enhanced its stimulatory effect on SRF-dependent transcriptional activation. These results suggest a connection between Ca(2+)-signaling via excitation-contraction coupling and the regulation of STARS-mediated gene expression in muscles. Copyright © 2016 Elsevier Ltd. All rights reserved.

Comparison of bioactive glass coated and hydroxyapatite coated titanium dental implants in the human jaw bone.

PubMed

Mistry, S; Kundu, D; Datta, S; Basu, D

2011-03-01

Current trends in clinical dental implant therapy include modification of titanium surfaces for the purpose of improving osseointegration by different additive (bioactive coatings) and subtractive processes (acid etching, grit-blasting). The aim of this study was to evaluate and compare the behaviour of hydroxyapatite and the newly developed bioactive glass coated implants (62 implants) in osseous tissue following implantation in 31 patients. Bioactive glass and hydroxyapatite was suitably coated on titanium alloy. Hydroxyapatite coating was applied on the implant surface by air microplasma spray technique and bioactive glass coating was applied by vitreous enamelling technique. The outcome was assessed up to 12 months after prosthetic loading using different clinical and radiological parameters. Hydroxyapatite and bioactive glass coating materials were non-toxic and biocompatible. Overall results showed that bioactive glass coated implants were as equally successful as hydroxyapatite in achieving osseointegration and supporting final restorations. The newly developed bioactive glass is a good alternative coating material for dental implants. © 2011 Australian Dental Association.

Newly discovered ebola virus associated with hemorrhagic fever outbreak in Uganda.

PubMed

Towner, Jonathan S; Sealy, Tara K; Khristova, Marina L; Albariño, César G; Conlan, Sean; Reeder, Serena A; Quan, Phenix-Lan; Lipkin, W Ian; Downing, Robert; Tappero, Jordan W; Okware, Samuel; Lutwama, Julius; Bakamutumaho, Barnabas; Kayiwa, John; Comer, James A; Rollin, Pierre E; Ksiazek, Thomas G; Nichol, Stuart T

2008-11-01

Over the past 30 years, Zaire and Sudan ebolaviruses have been responsible for large hemorrhagic fever (HF) outbreaks with case fatalities ranging from 53% to 90%, while a third species, Côte d'Ivoire ebolavirus, caused a single non-fatal HF case. In November 2007, HF cases were reported in Bundibugyo District, Western Uganda. Laboratory investigation of the initial 29 suspect-case blood specimens by classic methods (antigen capture, IgM and IgG ELISA) and a recently developed random-primed pyrosequencing approach quickly identified this to be an Ebola HF outbreak associated with a newly discovered ebolavirus species (Bundibugyo ebolavirus) distantly related to the Côte d'Ivoire ebolavirus found in western Africa. Due to the sequence divergence of this new virus relative to all previously recognized ebolaviruses, these findings have important implications for design of future diagnostic assays to monitor Ebola HF disease in humans and animals, and ongoing efforts to develop effective antivirals and vaccines.

Newly Discovered Ebola Virus Associated with Hemorrhagic Fever Outbreak in Uganda

PubMed Central

Towner, Jonathan S.; Sealy, Tara K.; Khristova, Marina L.; Albariño, César G.; Conlan, Sean; Reeder, Serena A.; Quan, Phenix-Lan; Lipkin, W. Ian; Downing, Robert; Tappero, Jordan W.; Okware, Samuel; Lutwama, Julius; Bakamutumaho, Barnabas; Kayiwa, John; Comer, James A.; Rollin, Pierre E.; Ksiazek, Thomas G.; Nichol, Stuart T.

2008-01-01

Over the past 30 years, Zaire and Sudan ebolaviruses have been responsible for large hemorrhagic fever (HF) outbreaks with case fatalities ranging from 53% to 90%, while a third species, Côte d'Ivoire ebolavirus, caused a single non-fatal HF case. In November 2007, HF cases were reported in Bundibugyo District, Western Uganda. Laboratory investigation of the initial 29 suspect-case blood specimens by classic methods (antigen capture, IgM and IgG ELISA) and a recently developed random-primed pyrosequencing approach quickly identified this to be an Ebola HF outbreak associated with a newly discovered ebolavirus species (Bundibugyo ebolavirus) distantly related to the Côte d'Ivoire ebolavirus found in western Africa. Due to the sequence divergence of this new virus relative to all previously recognized ebolaviruses, these findings have important implications for design of future diagnostic assays to monitor Ebola HF disease in humans and animals, and ongoing efforts to develop effective antivirals and vaccines. PMID:19023410

Investigation into adamantane-based M2 inhibitors with FB-QSAR.

PubMed

Wei, Hang; Wang, Cheng-Hua; Du, Qi-Shi; Meng, Jianzong; Chou, Kuo-Chen

2009-07-01

Because of their high resistance rate to the existing drugs, influenza A viruses have become a threat to human beings. It is known that the replication of influenza A viruses needs a pH-gated proton channel, the so-called M2 channel. Therefore, to develop effective drugs against influenza A, the most logic strategy is to inhibit the M2 channel. Recently, the atomic structure of the M2 channel was determined by NMR spectroscopy (Schnell, J.R. and Chou, J.J., Nature, 2008, 451, 591-595). The high-resolution NMR structure has provided a solid basis for structure-based drug design approaches. In this study, a benchmark dataset has been constructed that contains 34 newly-developed adamantane-based M2 inhibitors and covers considerable structural diversities and wide range of bioactivities. Based on these compounds, an in-depth analysis was performed with the newly developed fragment-based quantitative structure-activity relationship (FB-QSAR) algorithm. The results thus obtained provide useful insights for dealing with the drug-resistant problem and designing effective adamantane-based antiflu drugs.

Individualized pain medicine

PubMed Central

Kim, Hyungsuk; Dionne, Raymond A.

2010-01-01

Since the first draft of the human genome was published 10 years ago, scientists have tried to develop new treatment strategies for various types of diseases based on individual genomes. It is called personalized (or individualized) medicine and is expected to increase efficacy and reduce adverse reactions of drugs. Much progress has been made with newly developed technologies, though individualized pain medicine is still far from realization. Efforts on the integrative genomic analyses along with understandings of interactions between other related factors such as environment will eventually translate complex genomic information into individualized pain medicine. PMID:21399745

Portable two-channel PPG cardiovascular sensor device

NASA Astrophysics Data System (ADS)

Spigulis, Janis; Erts, Renars; Ozols, Maris

2003-10-01

A portable sensor device for simultaneous detection and processing of skin-remitted optical signals from any two sites of the body has been developed and tested. The photoplethysmography (PPG) principle was applied to follow the dilatation and contraction of skin blood vessels during the cardiac cycle. The newly developed two-channel approach allows to estimate the vascular blood flow resistance by analysis of time shifts between the PPG pulses detected at different body sites. Potential of the sensor device for express-assessment of human cardio-vascular condition and for body fitness tests has been demonstrated.

Radioimmunoassay of neuropeptide Y.

PubMed

Allen, J M; Yeats, J C; Adrian, T E; Bloom, S R

1984-01-01

The development of a radioimmunoassay to the newly isolated peptide, neuropeptide Y is described. Four separate antisera have been developed using different immunisation schedules. Two of these antisera (YNI and YNIO) are directed to the C-terminal region of the peptide and cross-react with the related peptide PYY, whereas YN7 is specific being directed to the N-terminal region of NPY, YN6 is similarly specific for NPY, but is unable to bind the available fragments. These four antisera provide similar results for determination of NPY immunoreactivity within porcine brain extracts, however YN6 consistently undervalues all extracts from the other species examined (human, rat, guinea pig, cat and mouse). Chromatographic analysis by means of reverse phase high pressure liquid chromatography (HPLC) shows that NPY immunoreactivity of human extracts elutes in an earlier position than the porcine standard. It seems likely therefore that human and porcine NPY differ in their amino acid sequences.

Inverse colloidal crystal membranes for hydrophobic interaction membrane chromatography.

PubMed

Vu, Anh T; Wang, Xinying; Wickramasinghe, S Ranil; Yu, Bing; Yuan, Hua; Cong, Hailin; Luo, Yongli; Tang, Jianguo

2015-08-01

Hydrophobic interaction membrane chromatography has gained interest due to its excellent performance in the purification of humanized monoclonal antibodies. The membrane material used in hydrophobic interaction membrane chromatography has typically been commercially available polyvinylidene fluoride. In this contribution, newly developed inverse colloidal crystal membranes that have uniform pores, high porosity and, therefore, high surface area for protein binding are used as hydrophobic interaction membrane chromatography membranes for humanized monoclonal antibody immunoglobulin G purification. The capacity of the inverse colloidal crystal membranes developed here is up to ten times greater than commercially available polyvinylidene fluoride membranes with a similar pore size. This work highlights the importance of developing uniform pore size high porosity membranes in order to maximize the capacity of hydrophobic interaction membrane chromatography. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Nilotinib and Imatinib Are Comparably Effective in Reducing Growth of Human Eosinophil Leukemia Cells in a Newly Established Xenograft Model

PubMed Central

Salamon, Johannes; Thamer, Mohammed; Herrmann, Harald; Valent, Peter; Schumacher, Udo; Ullrich, Sebastian

2012-01-01

We developed a xenograft model of human Chronic Eosinophilic Leukemia (CEL) to study disease progression and remission-induction under therapy with tyrosine kinase inhibitors using imatinib and nilotinib as examples. The FIP1L1/PDGFRA+ human CEL cell lineEOL-1 was injected intravenously into scid mice, and MR imaging and FACS analysis of mouse blood samples were performed to monitor disease development and the effects of imatinib and nilotinib. Organ infiltration was analyzed in detail by immunohistochemistry after sacrifice. All animals developed CEL and within one week of therapy, complete remissions were seen with both imatinib and nilotinib, resulting in reduced total tumor volumes by MR-imaging and almost complete disappearance of EOL-1 cells in the peripheral blood and in tissues. The new model system is feasible for the evaluation of new tyrosine kinase inhibitors and our data suggest that nilotinib may be a valuable additional targeted drug active in patients with FIP1L1/PDGFRA+ CEL. PMID:22348015

Broad neutralizing human monoclonal antibodies against influenza virus from vaccinated healthy donors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kubota-Koketsu, Ritsuko; Mizuta, Hiroyuki; Oshita, Masatoshi

2009-09-11

Human monoclonal antibodies (HuMAbs) prepared from patients with viral infections could provide information on human epitopes important for the development of vaccines as well as potential therapeutic applications. Through the fusion of peripheral blood mononuclear cells from a total of five influenza-vaccinated volunteers, with newly developed murine-human chimera fusion partner cells, named SPYMEG, we obtained 10 hybridoma clones stably producing anti-influenza virus antibodies: one for influenza A H1N1, four for influenza A H3N2 and five for influenza B. Surprisingly, most of the HuMAbs showed broad reactivity within subtype and four (two for H3N2 and two for B) showed broad neutralizingmore » ability. Importantly, epitope mapping revealed that the two broad neutralizing antibodies to H3N2 derived from different donors recognized the same epitope located underneath the receptor-binding site of the hemagglutinin globular region that is highly conserved among H3N2 strains.« less

Sensing Pressure Distribution on a Lower-Limb Exoskeleton Physical Human-Machine Interface

PubMed Central

De Rossi, Stefano Marco Maria; Vitiello, Nicola; Lenzi, Tommaso; Ronsse, Renaud; Koopman, Bram; Persichetti, Alessandro; Vecchi, Fabrizio; Ijspeert, Auke Jan; van der Kooij, Herman; Carrozza, Maria Chiara

2011-01-01

A sensory apparatus to monitor pressure distribution on the physical human-robot interface of lower-limb exoskeletons is presented. We propose a distributed measure of the interaction pressure over the whole contact area between the user and the machine as an alternative measurement method of human-robot interaction. To obtain this measure, an array of newly-developed soft silicone pressure sensors is inserted between the limb and the mechanical interface that connects the robot to the user, in direct contact with the wearer’s skin. Compared to state-of-the-art measures, the advantage of this approach is that it allows for a distributed measure of the interaction pressure, which could be useful for the assessment of safety and comfort of human-robot interaction. This paper presents the new sensor and its characterization, and the development of an interaction measurement apparatus, which is applied to a lower-limb rehabilitation robot. The system is calibrated, and an example its use during a prototypical gait training task is presented. PMID:22346574

Marine Indole Alkaloids

PubMed Central

Netz, Natalie; Opatz, Till

2015-01-01

Marine indole alkaloids comprise a large and steadily growing group of secondary metabolites. Their diverse biological activities make many compounds of this class attractive starting points for pharmaceutical development. Several marine-derived indoles were found to possess cytotoxic, antineoplastic, antibacterial and antimicrobial activities, in addition to the action on human enzymes and receptors. The newly isolated indole alkaloids of marine origin since the last comprehensive review in 2003 are reported, and biological aspects will be discussed. PMID:26287214

Genome Science and Personalized Cancer Treatment

ScienceCinema

Gray, Joe

2017-12-09

August 4, 2009 Berkeley Lab lecture: Results from the Human Genome Project are enabling scientists to understand how individual cancers form and progress. This information, when combined with newly developed drugs, can optimize the treatment of individual cancers. Joe Gray, director of Berkeley Labs Life Sciences Division and Associate Laboratory Director for Life and Environmental Sciences, will focus on this approach, its promise, and its current roadblocks — particularly with regard to breast cancer.

Oak Ridge National Laboratory Office of International Nuclear Safeguards: Human Capital Development Activity in FY16

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gilligan, Kimberly V.; Gaudet, Rachel N.

In 2007, the U.S. Department of Energy National Nuclear Security Administration (DOE NNSA) Office of Nonproliferation and Arms Control (NPAC) completed a comprehensive review of the current and potential future challenges facing the international safeguards system. One of the report’s key recommendations was for DOE NNSA to launch a major new program to revitalize the international safeguards technology and human resource base. In 2007, at the International Atomic Energy Agency (IAEA) General Conference, then Secretary of Energy Samuel W. Bodman announced the newly created Next Generation Safeguards Initiative (NGSI). NGSI consists of five program elements: policy development and outreach, conceptsmore » and approaches, technology and analytical methodologies, human capital development (HCD), and infrastructure development. This report addresses the HCD component of NGSI. The goal of the HCD component as defined in the NNSA Program Plan is “to revitalize and expand the international safeguards human capital base by attracting and training a new generation of talent.” The major objectives listed in the HCD goal include education and training, outreach to universities and professional societies, postdoctoral appointments, and summer internships at national laboratories.« less

Derivation and characterization of Chinese human embryonic stem cell line with high potential to differentiate into pancreatic and hepatic cells.

PubMed

Shi, Cheng; Shen, Huan; Jiang, Wei; Song, Zhi-Hua; Wang, Cheng-Yan; Wei, Li-Hui

2011-04-01

Human embryonic stem cells have prospective uses in regenerative medicine and drug screening. Every human embryonic stem cell line has its own genetic background, which determines its specific ability for differentiation as well as susceptibility to drugs. It is necessary to compile many human embryonic stem cell lines with various backgrounds for future clinical use, especially in China due to its large population. This study contributes to isolating new Chinese human embryonic stem cell lines with clarified directly differentiation ability. Donated embryos that exceeded clinical use in our in vitro fertilization-embryo transfer (IVF-ET) center were collected to establish human embryonic stem cells lines with informed consent. The classic growth factors of basic fibroblast growth factor (bFGF) and recombinant human leukaemia inhibitory factor (hLIF) for culturing embryonic stem cells were used to capture the stem cells from the plated embryos. Mechanical and enzymetic methods were used to propagate the newly established human embryonic stem cells line. The new cell line was checked for pluripotent characteristics with detecting the expression of stemness genes and observing spontaneous differentiation both in vitro and in vivo. Finally similar step-wise protocols from definitive endoderm to target specific cells were used to check the cell line's ability to directly differentiate into pancreatic and hepatic cells. We generated a new Chinese human embryonic stem cells line, CH1. This cell line showed the same characteristics as other reported Chinese human embryonic stem cells lines: normal morphology, karyotype and pluripotency in vitro and in vivo. The CH1 cells could be directly differentiated towards pancreatic and hepatic cells with equal efficiency compared to the H1 cell line. This newly established Chinese cell line, CH1, which is pluripotent and has high potential to differentiate into pancreatic and hepatic cells, will provide a useful tool for embryo development research, along with clinical treatments for diabetes and some hepatic diseases.

Bug breakfast in the bulletin: human papilloma virus.

PubMed

Wallace, Cate; Weisberg, Edith; McCaffery, Kirsten

2007-01-01

The Bug Breakfast topic for October was Human Papilloma Virus (HPV). The presenters covered the epidemiology of HPV, the newly introduced HPV vaccine and social and psychological issues relating to HPV vaccination.

Development of Cross-Assembly Phage PCR-Based Methods ...

EPA Pesticide Factsheets

Technologies that can characterize human fecal pollution in environmental waters offer many advantages over traditional general indicator approaches. However, many human-associated methods cross-react with non-human animal sources and lack suitable sensitivity for fecal source identification applications. The genome of a newly discovered bacteriophage (~97 kbp), the Cross-Assembly phage or “crAssphage”, assembled from a human gut metagenome DNA sequence library is predicted to be both highly abundant and predominately occur in human feces suggesting that this double stranded DNA virus may be an ideal human fecal pollution indicator. We report the development of two human-associated crAssphage endpoint PCR methods (crAss056 and crAss064). A shotgun strategy was employed where 384 candidate primers were designed to cover ~41 kbp of the crAssphage genome deemed favorable for method development based on a series of bioinformatics analyses. Candidate primers were subjected to three rounds of testing to evaluate assay optimization, specificity, limit of detection (LOD95), geographic variability, and performance in environmental water samples. The top two performing candidate primer sets exhibited 100% specificity (n = 70 individual samples from 8 different animal species), >90% sensitivity (n = 10 raw sewage samples from different geographic locations), LOD95 of 0.01 ng/µL of total DNA per reaction, and successfully detected human fecal pollution in impaired envi

Genome Science and Personalized Cancer Treatment (LBNL Summer Lecture Series)

ScienceCinema

Gray, Joe [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Sciences Division and Associate Lab. Director for Life and Environmental Sciences

2018-05-04

Summer Lecture Series 2009: Results from the Human Genome Project are enabling scientists to understand how individual cancers form and progress. This information, when combined with newly developed drugs, can optimize the treatment of individual cancers. Joe Gray, director of Berkeley Labs Life Sciences Division and Associate Laboratory Director for Life and Environmental Sciences, will focus on this approach, its promise, and its current roadblocks — particularly with regard to breast cancer.

Enterovirus 71 infection of human airway organoids reveals VP1-145 as a viral infectivity determinant.

PubMed

van der Sanden, Sabine M G; Sachs, Norman; Koekkoek, Sylvie M; Koen, Gerrit; Pajkrt, Dasja; Clevers, Hans; Wolthers, Katja C

2018-05-09

Human enteroviruses frequently cause severe diseases in children. Human enteroviruses are transmitted via the fecal-oral route and respiratory droplets, and primary replication occurs in the gastro-intestinal and respiratory tracts; however, how enteroviruses infect these sites is largely unknown. Human intestinal organoids have recently proven to be valuable tools for studying enterovirus-host interactions in the intestinal tract. In this study, we demonstrated the susceptibility of a newly developed human airway organoid model for enterovirus 71 (EV71) infection. We showed for the first time in a human physiological model that EV71 replication kinetics are strain-dependent. A glutamine at position 145 of the VP1 capsid protein was identified as a key determinant of infectivity, and residues VP1-98K and VP1-104D were identified as potential infectivity markers. The results from this study provide new insights into EV71 infectivity in the human airway epithelia and demonstrate the value of organoid technology for virus research.

Systemic regulation of leaf anatomical structure, photosynthetic performance, and high-light tolerance in sorghum.

PubMed

Jiang, Chuang-Dao; Wang, Xin; Gao, Hui-Yuan; Shi, Lei; Chow, Wah Soon

2011-03-01

Leaf anatomy of C3 plants is mainly regulated by a systemic irradiance signal. Since the anatomical features of C4 plants are different from that of C3 plants, we investigated whether the systemic irradiance signal regulates leaf anatomical structure and photosynthetic performance in sorghum (Sorghum bicolor), a C4 plant. Compared with growth under ambient conditions (A), no significant changes in anatomical structure were observed in newly developed leaves by shading young leaves alone (YS). Shading mature leaves (MS) or whole plants (S), on the other hand, caused shade-leaf anatomy in newly developed leaves. By contrast, chloroplast ultrastructure in developing leaves depended only on their local light conditions. Functionally, shading young leaves alone had little effect on their net photosynthetic capacity and stomatal conductance, but shading mature leaves or whole plants significantly decreased these two parameters in newly developed leaves. Specifically, the net photosynthetic rate in newly developed leaves exhibited a positive linear correlation with that of mature leaves, as did stomatal conductance. In MS and S treatments, newly developed leaves exhibited severe photoinhibition under high light. By contrast, newly developed leaves in A and YS treatments were more resistant to high light relative to those in MS- and S-treated seedlings. We suggest that (1) leaf anatomical structure, photosynthetic capacity, and high-light tolerance in newly developed sorghum leaves were regulated by a systemic irradiance signal from mature leaves; and (2) chloroplast ultrastructure only weakly influenced the development of photosynthetic capacity and high-light tolerance. The potential significance of the regulation by a systemic irradiance signal is discussed.

Equation Discovery for Model Identification in Respiratory Mechanics of the Mechanically Ventilated Human Lung

NASA Astrophysics Data System (ADS)

Ganzert, Steven; Guttmann, Josef; Steinmann, Daniel; Kramer, Stefan

Lung protective ventilation strategies reduce the risk of ventilator associated lung injury. To develop such strategies, knowledge about mechanical properties of the mechanically ventilated human lung is essential. This study was designed to develop an equation discovery system to identify mathematical models of the respiratory system in time-series data obtained from mechanically ventilated patients. Two techniques were combined: (i) the usage of declarative bias to reduce search space complexity and inherently providing the processing of background knowledge. (ii) A newly developed heuristic for traversing the hypothesis space with a greedy, randomized strategy analogical to the GSAT algorithm. In 96.8% of all runs the applied equation discovery system was capable to detect the well-established equation of motion model of the respiratory system in the provided data. We see the potential of this semi-automatic approach to detect more complex mathematical descriptions of the respiratory system from respiratory data.

Epigenetic Mistakes in Neurodevelopmental Disorders.

PubMed

Mastrototaro, Giuseppina; Zaghi, Mattia; Sessa, Alessandro

2017-04-01

Epigenetics is the array of the chromatin modifications that customize in cell-, stage-, or condition-specific manner the information encloses in plain DNA molecules. Increasing evidences suggest the importance of epigenetic mechanisms for development and maintenance of central nervous system. In fact, a large number of newly discovered genetic causes of neurodevelopmental disorders such as intellectual disability, autism spectrum disorders, and many other syndromes are mutations within genes encoding for chromatin remodeling enzymes. Here, we review recent findings on the epigenetic origin of human diseases, with emphasis on disorders that affect development of the nervous system, and discuss novel therapeutic avenues that target epigenetic mechanisms.

Harvesting energy from the natural vibration of human walking.

PubMed

Yang, Weiqing; Chen, Jun; Zhu, Guang; Yang, Jin; Bai, Peng; Su, Yuanjie; Jing, Qingsheng; Cao, Xia; Wang, Zhong Lin

2013-12-23

The triboelectric nanogenerator (TENG), a unique technology for harvesting ambient mechanical energy based on the triboelectric effect, has been proven to be a cost-effective, simple, and robust approach for self-powered systems. However, a general challenge is that the output current is usually low. Here, we demonstrated a rationally designed TENG with integrated rhombic gridding, which greatly improved the total current output owing to the structurally multiplied unit cells connected in parallel. With the hybridization of both the contact-separation mode and sliding electrification mode among nanowire arrays and nanopores fabricated onto the surfaces of two contact plates, the newly designed TENG produces an open-circuit voltage up to 428 V, and a short-circuit current of 1.395 mA with the peak power density of 30.7 W/m(2). Relying on the TENG, a self-powered backpack was developed with a vibration-to-electric energy conversion efficiency up to 10.62(±1.19) %. And it was also demonstrated as a direct power source for instantaneously lighting 40 commercial light-emitting diodes by harvesting the vibration energy from natural human walking. The newly designed TENG can be a mobile power source for field engineers, explorers, and disaster-relief workers.

Plasmodium knowlesi: from severe zoonosis to animal model.

PubMed

Cox-Singh, Janet; Culleton, Richard

2015-06-01

Plasmodium knowlesi malaria is a newly described zoonosis in Southeast Asia. Similarly to Plasmodium falciparum, P. knowlesi can reach high parasitaemia in the human host and both species cause severe and fatal illness. Interpretation of host-parasite interactions in studies of P. knowlesi malaria adds a counterpoint to studies on P. falciparum. However, there is no model system for testing the resulting hypotheses on malaria pathophysiology or for developing new interventions. Plasmodium knowlesi is amenable to genetic manipulation in vitro and several nonhuman primate species are susceptible to experimental infection. Here, we make a case for drawing on P. knowlesi as both a human pathogen and an experimental model to lift the roadblock between malaria research and its translation into human health benefits. Copyright © 2015 Elsevier Ltd. All rights reserved.

Genome-wide association analysis identifies six new loci associated with forced vital capacity.

PubMed

Loth, Daan W; Soler Artigas, María; Gharib, Sina A; Wain, Louise V; Franceschini, Nora; Koch, Beate; Pottinger, Tess D; Smith, Albert Vernon; Duan, Qing; Oldmeadow, Chris; Lee, Mi Kyeong; Strachan, David P; James, Alan L; Huffman, Jennifer E; Vitart, Veronique; Ramasamy, Adaikalavan; Wareham, Nicholas J; Kaprio, Jaakko; Wang, Xin-Qun; Trochet, Holly; Kähönen, Mika; Flexeder, Claudia; Albrecht, Eva; Lopez, Lorna M; de Jong, Kim; Thyagarajan, Bharat; Alves, Alexessander Couto; Enroth, Stefan; Omenaas, Ernst; Joshi, Peter K; Fall, Tove; Viñuela, Ana; Launer, Lenore J; Loehr, Laura R; Fornage, Myriam; Li, Guo; Wilk, Jemma B; Tang, Wenbo; Manichaikul, Ani; Lahousse, Lies; Harris, Tamara B; North, Kari E; Rudnicka, Alicja R; Hui, Jennie; Gu, Xiangjun; Lumley, Thomas; Wright, Alan F; Hastie, Nicholas D; Campbell, Susan; Kumar, Rajesh; Pin, Isabelle; Scott, Robert A; Pietiläinen, Kirsi H; Surakka, Ida; Liu, Yongmei; Holliday, Elizabeth G; Schulz, Holger; Heinrich, Joachim; Davies, Gail; Vonk, Judith M; Wojczynski, Mary; Pouta, Anneli; Johansson, Asa; Wild, Sarah H; Ingelsson, Erik; Rivadeneira, Fernando; Völzke, Henry; Hysi, Pirro G; Eiriksdottir, Gudny; Morrison, Alanna C; Rotter, Jerome I; Gao, Wei; Postma, Dirkje S; White, Wendy B; Rich, Stephen S; Hofman, Albert; Aspelund, Thor; Couper, David; Smith, Lewis J; Psaty, Bruce M; Lohman, Kurt; Burchard, Esteban G; Uitterlinden, André G; Garcia, Melissa; Joubert, Bonnie R; McArdle, Wendy L; Musk, A Bill; Hansel, Nadia; Heckbert, Susan R; Zgaga, Lina; van Meurs, Joyce B J; Navarro, Pau; Rudan, Igor; Oh, Yeon-Mok; Redline, Susan; Jarvis, Deborah L; Zhao, Jing Hua; Rantanen, Taina; O'Connor, George T; Ripatti, Samuli; Scott, Rodney J; Karrasch, Stefan; Grallert, Harald; Gaddis, Nathan C; Starr, John M; Wijmenga, Cisca; Minster, Ryan L; Lederer, David J; Pekkanen, Juha; Gyllensten, Ulf; Campbell, Harry; Morris, Andrew P; Gläser, Sven; Hammond, Christopher J; Burkart, Kristin M; Beilby, John; Kritchevsky, Stephen B; Gudnason, Vilmundur; Hancock, Dana B; Williams, O Dale; Polasek, Ozren; Zemunik, Tatijana; Kolcic, Ivana; Petrini, Marcy F; Wjst, Matthias; Kim, Woo Jin; Porteous, David J; Scotland, Generation; Smith, Blair H; Viljanen, Anne; Heliövaara, Markku; Attia, John R; Sayers, Ian; Hampel, Regina; Gieger, Christian; Deary, Ian J; Boezen, H Marike; Newman, Anne; Jarvelin, Marjo-Riitta; Wilson, James F; Lind, Lars; Stricker, Bruno H; Teumer, Alexander; Spector, Timothy D; Melén, Erik; Peters, Marjolein J; Lange, Leslie A; Barr, R Graham; Bracke, Ken R; Verhamme, Fien M; Sung, Joohon; Hiemstra, Pieter S; Cassano, Patricia A; Sood, Akshay; Hayward, Caroline; Dupuis, Josée; Hall, Ian P; Brusselle, Guy G; Tobin, Martin D; London, Stephanie J

2014-07-01

Forced vital capacity (FVC), a spirometric measure of pulmonary function, reflects lung volume and is used to diagnose and monitor lung diseases. We performed genome-wide association study meta-analysis of FVC in 52,253 individuals from 26 studies and followed up the top associations in 32,917 additional individuals of European ancestry. We found six new regions associated at genome-wide significance (P < 5 × 10(-8)) with FVC in or near EFEMP1, BMP6, MIR129-2-HSD17B12, PRDM11, WWOX and KCNJ2. Two loci previously associated with spirometric measures (GSTCD and PTCH1) were related to FVC. Newly implicated regions were followed up in samples from African-American, Korean, Chinese and Hispanic individuals. We detected transcripts for all six newly implicated genes in human lung tissue. The new loci may inform mechanisms involved in lung development and the pathogenesis of restrictive lung disease.

Genome-wide association analysis identifies six new loci associated with forced vital capacity

PubMed Central

Loth, Daan W.; Artigas, María Soler; Gharib, Sina A.; Wain, Louise V.; Franceschini, Nora; Koch, Beate; Pottinger, Tess; Smith, Albert Vernon; Duan, Qing; Oldmeadow, Chris; Lee, Mi Kyeong; Strachan, David P.; James, Alan L.; Huffman, Jennifer E.; Vitart, Veronique; Ramasamy, Adaikalavan; Wareham, Nicholas J.; Kaprio, Jaakko; Wang, Xin-Qun; Trochet, Holly; Kähönen, Mika; Flexeder, Claudia; Albrecht, Eva; Lopez, Lorna M.; de Jong, Kim; Thyagarajan, Bharat; Alves, Alexessander Couto; Enroth, Stefan; Omenaas, Ernst; Joshi, Peter K.; Fall, Tove; Viňuela, Ana; Launer, Lenore J.; Loehr, Laura R.; Fornage, Myriam; Li, Guo; Wilk, Jemma B.; Tang, Wenbo; Manichaikul, Ani; Lahousse, Lies; Harris, Tamara B.; North, Kari E.; Rudnicka, Alicja R.; Hui, Jennie; Gu, Xiangjun; Lumley, Thomas; Wright, Alan F.; Hastie, Nicholas D.; Campbell, Susan; Kumar, Rajesh; Pin, Isabelle; Scott, Robert A.; Pietiläinen, Kirsi H.; Surakka, Ida; Liu, Yongmei; Holliday, Elizabeth G.; Schulz, Holger; Heinrich, Joachim; Davies, Gail; Vonk, Judith M.; Wojczynski, Mary; Pouta, Anneli; Johansson, Åsa; Wild, Sarah H.; Ingelsson, Erik; Rivadeneira, Fernando; Völzke, Henry; Hysi, Pirro G.; Eiriksdottir, Gudny; Morrison, Alanna C.; Rotter, Jerome I.; Gao, Wei; Postma, Dirkje S.; White, Wendy B.; Rich, Stephen S.; Hofman, Albert; Aspelund, Thor; Couper, David; Smith, Lewis J.; Psaty, Bruce M.; Lohman, Kurt; Burchard, Esteban G.; Uitterlinden, André G.; Garcia, Melissa; Joubert, Bonnie R.; McArdle, Wendy L.; Musk, A. Bill; Hansel, Nadia; Heckbert, Susan R.; Zgaga, Lina; van Meurs, Joyce B.J.; Navarro, Pau; Rudan, Igor; Oh, Yeon-Mok; Redline, Susan; Jarvis, Deborah; Zhao, Jing Hua; Rantanen, Taina; O’Connor, George T.; Ripatti, Samuli; Scott, Rodney J.; Karrasch, Stefan; Grallert, Harald; Gaddis, Nathan C.; Starr, John M.; Wijmenga, Cisca; Minster, Ryan L.; Lederer, David J.; Pekkanen, Juha; Gyllensten, Ulf; Campbell, Harry; Morris, Andrew P.; Gläser, Sven; Hammond, Christopher J.; Burkart, Kristin M.; Beilby, John; Kritchevsky, Stephen B.; Gudnason, Vilmundur; Hancock, Dana B.; Williams, O. Dale; Polasek, Ozren; Zemunik, Tatijana; Kolcic, Ivana; Petrini, Marcy F.; Wjst, Matthias; Kim, Woo Jin; Porteous, David J.; Scotland, Generation; Smith, Blair H.; Viljanen, Anne; Heliövaara, Markku; Attia, John R.; Sayers, Ian; Hampel, Regina; Gieger, Christian; Deary, Ian J.; Boezen, H. Marike; Newman, Anne; Jarvelin, Marjo-Riitta; Wilson, James F.; Lind, Lars; Stricker, Bruno H.; Teumer, Alexander; Spector, Timothy D.; Melén, Erik; Peters, Marjolein J.; Lange, Leslie A.; Barr, R. Graham; Bracke, Ken R.; Verhamme, Fien M.; Sung, Joohon; Hiemstra, Pieter S.; Cassano, Patricia A.; Sood, Akshay; Hayward, Caroline; Dupuis, Josée; Hall, Ian P.; Brusselle, Guy G.; Tobin, Martin D.; London, Stephanie J.

2014-01-01

Forced vital capacity (FVC), a spirometric measure of pulmonary function, reflects lung volume and is used to diagnose and monitor lung diseases. We performed genome-wide association study meta-analysis of FVC in 52,253 individuals from 26 studies and followed up the top associations in 32,917 additional individuals of European ancestry. We found six new regions associated at genome-wide significance (P < 5 × 10−8) with FVC in or near EFEMP1, BMP6, MIR-129-2/HSD17B12, PRDM11, WWOX, and KCNJ2. Two (GSTCD and PTCH1) loci previously associated with spirometric measures were related to FVC. Newly implicated regions were followed-up in samples of African American, Korean, Chinese, and Hispanic individuals. We detected transcripts for all six newly implicated genes in human lung tissue. The new loci may inform mechanisms involved in lung development and pathogenesis of restrictive lung disease. PMID:24929828

Three-dimensional Culture of Human Airway Epithelium in Matrigel for Evaluation of Human Rhinovirus C and Bocavirus Infections.

PubMed

Chen, A Xiong; Xie, Guang Cheng; Pan, Dong; DU, Ya Rong; Pang, Li Li; Song, Jing Dong; Duan, Zhao Jun; Hu, Bu Rong

2018-02-01

Newly identified human rhinovirus C (HRV-C) and human bocavirus (HBoV) cannot propagate in vitro in traditional cell culture models; thus obtaining knowledge about these viruses and developing related vaccines are difficult. Therefore, it is necessary to develop a novel platform for the propagation of these types of viruses. A platform for culturing human airway epithelia in a three-dimensional (3D) pattern using Matrigel as scaffold was developed. The features of 3D culture were identified by immunochemical staining and transmission electron microscopy. Nucleic acid levels of HRV-C and HBoV in 3D cells at designated time points were quantitated by real-time polymerase chain reaction (PCR). Levels of cytokines, whose secretion was induced by the viruses, were measured by ELISA. Properties of bronchial-like tissues, such as the expression of biomarkers CK5, ZO-1, and PCK, and the development of cilium-like protuberances indicative of the human respiration tract, were observed in 3D-cultured human airway epithelial (HAE) cultures, but not in monolayer-cultured cells. Nucleic acid levels of HRV-C and HBoV and levels of virus-induced cytokines were also measured using the 3D culture system. Our data provide a preliminary indication that the 3D culture model of primary epithelia using a Matrigel scaffold in vitro can be used to propagate HRV-C and HBoV. Copyright © 2018 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

Microvesicating effects of sulfur mustard on an in vitro human skin model.

PubMed

Hayden, Patrick J; Petrali, John P; Stolper, Gina; Hamilton, Tracey A; Jackson, George R; Wertz, Philip W; Ito, Susumu; Smith, William J; Klausner, Mitchell

2009-10-01

Bis-(beta-chloroethyl) sulfide (SM) is a potent skin vesicant previously used for chemical warfare. Progress in determination of the mechanistic basis of SM pathology, and development of prophylactic and/or therapeutic countermeasures to SM exposure has been hampered by lack of physiologically relevant models of human skin. The current work evaluated a newly developed tissue engineered full-thickness human skin model in a completely in vitro approach to investigation of SM-induced dermal pathology. The model was first characterized with regard to overall morphology, lipid composition, basement membrane (BM) composition and ultrastructural features that are important targets of SM pathologic activity. Well-developed BM ultrastructural features were observed at the dermal-epidermal junction (DEJ), thus demonstrating successful resolution of a primary deficiency of models previously evaluated for SM studies. Studies were then conducted to evaluate histopathological effects of SM on the model. Good replication of in vivo effects was observed, including apoptosis of basal keratinocytes (KC) and microblister formation at the DEJ. Tissue engineered skin models with well-developed basement membrane structures thus appear to be useful tools for in vitro mechanistic studies of SM vesicant activity and development of preventive/therapeutic approaches for SM pathology.

Evaluation of Two Commercial Enzyme-Linked Immunosorbent Assay Kits for the Detection of Human Circulating Metrnl.

PubMed

Zheng, Si-Li; Li, Zhi-Yong; Zhang, Zheng; Wang, Dong-Sheng; Xu, Jian; Miao, Chao-Yu

2018-04-01

Metrnl is a newly discovered secreted protein with neurotrophic activity and metabolic effect, while in earlier studies its circulating level in human was not explored. We evaluated two commercial enzyme-linked immunosorbent assay kits (DY7867-05, R&D Systems and SK00478-02, Aviscera Bioscience) for the detection of human circulating Metrnl. The DY7867-05 kit showed superiority over the SK00478-02 kit since it generated better curve fitting degree, smaller variation among tests, higher inter-assay reproducibility and better specificity, and could effectively detect human Metrnl in six types of blood samples. Subsequent analysis was performed using the DY7867-05 kit. Sample storage conditions were investigated. No gender difference in circulating Metrnl levels was found, while people with newly diagnosed type 2 diabetes mellitus (T2DM) had significantly lower Metrnl levels compared to the healthy controls.

Quantification of the Intracellular Life Time of Water Molecules to Measure Transport Rates of Human Aquaglyceroporins.

PubMed

Palmgren, Madelene; Hernebring, Malin; Eriksson, Stefanie; Elbing, Karin; Geijer, Cecilia; Lasič, Samo; Dahl, Peter; Hansen, Jesper S; Topgaard, Daniel; Lindkvist-Petersson, Karin

2017-12-01

Orthodox aquaporins are transmembrane channel proteins that facilitate rapid diffusion of water, while aquaglyceroporins facilitate the diffusion of small uncharged molecules such as glycerol and arsenic trioxide. Aquaglyceroporins play important roles in human physiology, in particular for glycerol metabolism and arsenic detoxification. We have developed a unique system applying the strain of the yeast Pichia pastoris, where the endogenous aquaporins/aquaglyceroporins have been removed and human aquaglyceroporins AQP3, AQP7, and AQP9 are recombinantly expressed enabling comparative permeability measurements between the expressed proteins. Using a newly established Nuclear Magnetic Resonance approach based on measurement of the intracellular life time of water, we propose that human aquaglyceroporins are poor facilitators of water and that the water transport efficiency is similar to that of passive diffusion across native cell membranes. This is distinctly different from glycerol and arsenic trioxide, where high glycerol transport efficiency was recorded.

Sweat Gland Progenitors in Development, Homeostasis, and Wound Repair

PubMed Central

Lu, Catherine; Fuchs, Elaine

2014-01-01

The human body is covered with several million sweat glands. These tiny coiled tubular skin appendages produce the sweat that is our primary source of cooling and hydration of the skin. Numerous studies have been published on their morphology and physiology. Until recently, however, little was known about how glandular skin maintains homeostasis and repairs itself after tissue injury. Here, we provide a brief overview of sweat gland biology, including newly identified reservoirs of stem cells in glandular skin and their activation in response to different types of injuries. Finally, we discuss how the genetics and biology of glandular skin has advanced our knowledge of human disorders associated with altered sweat gland activity. PMID:24492848

Annual banned-substance review: analytical approaches in human sports drug testing.

PubMed

Thevis, Mario; Kuuranne, Tiia; Geyer, Hans; Schänzer, Wilhelm

2010-04-01

The annual update of the list of prohibited substances and doping methods as issued by the World Anti-Doping Agency (WADA) allows the implementation of most recent considerations of performance manipulation and emerging therapeutics into human sports doping control programmes. The annual banned-substance review for human doping controls critically summarizes recent innovations in analytical approaches that support the efforts of convicting cheating athletes by improved or newly established methods that focus on known as well as newly outlawed substances and doping methods. In the current review, literature published between October 2008 and September 2009 reporting on new and/or enhanced procedures and techniques for doping analysis, as well as aspects relevant to the doping control arena, was considered to complement the 2009 annual banned-substance review.

Oncolytic Virotherapy as Emerging Immunotherapeutic Modality: Potential of Parvovirus H-1

PubMed Central

Moehler, Markus; Goepfert, Katrin; Heinrich, Bernd; Breitbach, Caroline J.; Delic, Maike; Galle, Peter Robert; Rommelaere, Jean

2014-01-01

Human tumors develop multiple strategies to evade recognition and efficient suppression by the immune system. Therefore, a variety of immunotherapeutic strategies have been developed to reactivate and reorganize the human immune system. The recent development of new antibodies against immune check points may help to overcome the immune silencing induced by human tumors. Some of these antibodies have already been approved for treatment of various solid tumor entities. Interestingly, targeting antibodies may be combined with standard chemotherapy or radiation protocols. Furthermore, recent evidence indicates that intratumoral or intravenous injections of replicative oncolytic viruses such as herpes simplex-, pox-, parvo-, or adenoviruses may also reactivate the human immune system. By generating tumor cell lysates in situ, oncolytic viruses overcome cellular tumor resistance mechanisms and induce immunogenic tumor cell death resulting in the recognition of newly released tumor antigens. This is in particular the case of the oncolytic parvovirus H-1 (H-1PV), which is able to kill human tumor cells and stimulate an anti-tumor immune response through increased presentation of tumor-associated antigens, maturation of dendritic cells, and release of pro-inflammatory cytokines. Current research and clinical studies aim to assess the potential of oncolytic virotherapy and its combination with immunotherapeutic agents or conventional treatments to further induce effective antitumoral immune responses. PMID:24822170

An integrated platform for biomolecule interaction analysis

NASA Astrophysics Data System (ADS)

Jan, Chia-Ming; Tsai, Pei-I.; Chou, Shin-Ting; Lee, Shu-Sheng; Lee, Chih-Kung

2013-02-01

We developed a new metrology platform which can detect real-time changes in both a phase-interrogation mode and intensity mode of a SPR (surface plasmon resonance). We integrated a SPR and ellipsometer to a biosensor chip platform to create a new biomolecular interaction measurement mechanism. We adopted a conductive ITO (indium-tinoxide) film to the bio-sensor platform chip to expand the dynamic range and improve measurement accuracy. The thickness of the conductive film and the suitable voltage constants were found to enhance performance. A circularly polarized ellipsometry configuration was incorporated into the newly developed platform to measure the label-free interactions of recombinant human C-reactive protein (CRP) with immobilized biomolecule target monoclonal human CRP antibody at various concentrations. CRP was chosen as it is a cardiovascular risk biomarker and is an acute phase reactant as well as a specific prognostic indicator for inflammation. We found that the sensitivity of a phaseinterrogation SPR is predominantly dependent on the optimization of the sample incidence angle. The effect of the ITO layer effective index under DC and AC effects as well as an optimal modulation were experimentally performed and discussed. Our experimental results showed that the modulated dynamic range for phase detection was 10E-2 RIU based on a current effect and 10E-4 RIU based on a potential effect of which a 0.55 (°/RIU) measurement was found by angular-interrogation. The performance of our newly developed metrology platform was characterized to have a higher sensitivity and less dynamic range when compared to a traditional full-field measurement system.

Influence of Cultural, Organizational, and Automation Capability on Human Automation Trust: A Case Study of Auto-GCAS Experimental Test Pilots

NASA Technical Reports Server (NTRS)

Koltai, Kolina; Ho, Nhut; Masequesmay, Gina; Niedober, David; Skoog, Mark; Cacanindin, Artemio; Johnson, Walter; Lyons, Joseph

2014-01-01

This paper discusses a case study that examined the influence of cultural, organizational and automation capability upon human trust in, and reliance on, automation. In particular, this paper focuses on the design and application of an extended case study methodology, and on the foundational lessons revealed by it. Experimental test pilots involved in the research and development of the US Air Force's newly developed Automatic Ground Collision Avoidance System served as the context for this examination. An eclectic, multi-pronged approach was designed to conduct this case study, and proved effective in addressing the challenges associated with the case's politically sensitive and military environment. Key results indicate that the system design was in alignment with pilot culture and organizational mission, indicating the potential for appropriate trust development in operational pilots. These include the low-vulnerability/ high risk nature of the pilot profession, automation transparency and suspicion, system reputation, and the setup of and communications among organizations involved in the system development.

An Extended Case Study Methoology for Investigating Influence of Cultural, Organizational, and Automation Factors on Human-Automation Trust

NASA Technical Reports Server (NTRS)

Koltai, Kolina Sun; Ho, Nhut; Masequesmay, Gina; Niedober, David; Skoog, Mark; Johnson, Walter; Cacanindin, Artemio

2014-01-01

This paper discusses a case study that examined the influence of cultural, organizational and automation capability upon human trust in, and reliance on, automation. In particular, this paper focuses on the design and application of an extended case study methodology, and on the foundational lessons revealed by it. Experimental test pilots involved in the research and development of the US Air Forces newly developed Automatic Ground Collision Avoidance System served as the context for this examination. An eclectic, multi-pronged approach was designed to conduct this case study, and proved effective in addressing the challenges associated with the cases politically sensitive and military environment. Key results indicate that the system design was in alignment with pilot culture and organizational mission, indicating the potential for appropriate trust development in operational pilots. These include the low-vulnerabilityhigh risk nature of the pilot profession, automation transparency and suspicion, system reputation, and the setup of and communications among organizations involved in the system development.

Development of radiometric assays for quantification of enzyme activities of the key enzymes of thyroid hormones metabolism.

PubMed

Pavelka, S

2014-01-01

We newly elaborated and adapted several radiometric enzyme assays for the determination of activities of the key enzymes engaged in the biosynthesis (thyroid peroxidase, TPO) and metabolic transformations (conjugating enzymes and iodothyronine deiodinases, IDs) of thyroid hormones (THs) in the thyroid gland and in peripheral tissues, especially in white adipose tissue (WAT). We also elaborated novel, reliable radiometric methods for extremely sensitive determination of enzyme activities of IDs of types 1, 2 and 3 in microsomal fractions of different rat and human tissues, as well as in homogenates of cultured mammalian cells. The use of optimized TLC separation of radioactive products from the unconsumed substrates and film-less autoradiography of radiochromatograms, taking advantage of storage phosphor screens, enabled us to determine IDs enzyme activities as low as 10(-18) katals. In studies of the interaction of fluoxetine (Fluox) with the metabolism of THs, we applied adapted radiometric enzyme assays for iodothyronine sulfotransferases (ST) and uridine 5'-diphospho-glucuronyltransferase (UDP-GT). Fluox is the most frequently used representative of a new group of non-tricyclic antidepressant drugs--selective serotonin re-uptake inhibitors. We used the elaborated assays for quantification the effects of Fluox and for the assessment of the degree of potential induction of rat liver ST and/or UDP-GT enzyme activities by Fluox alone or in combination with T(3). Furthermore, we studied possible changes in IDs activities in murine adipose tissue under the conditions that promoted either tissue hypertrophy (obesogenic treatment) or involution (caloric restriction), and in response to leptin, using our newly developed radiometric enzyme assays for IDs. Our results suggest that deiodinase D1 has a functional role in WAT, with D1 possibly being involved in the control of adipose tissue metabolism and/or accumulation of the tissue. Significant positive correlation between specific enzyme activity of D1 in WAT and plasma leptin levels was found. The newly developed and adapted radiometric enzyme assays proved to be very useful tools for studies of factors modulating THs metabolism, not only in model animals but also in clinical studies of human obesity.

On Inertial Body Tracking in the Presence of Model Calibration Errors

PubMed Central

Miezal, Markus; Taetz, Bertram; Bleser, Gabriele

2016-01-01

In inertial body tracking, the human body is commonly represented as a biomechanical model consisting of rigid segments with known lengths and connecting joints. The model state is then estimated via sensor fusion methods based on data from attached inertial measurement units (IMUs). This requires the relative poses of the IMUs w.r.t. the segments—the IMU-to-segment calibrations, subsequently called I2S calibrations—to be known. Since calibration methods based on static poses, movements and manual measurements are still the most widely used, potentially large human-induced calibration errors have to be expected. This work compares three newly developed/adapted extended Kalman filter (EKF) and optimization-based sensor fusion methods with an existing EKF-based method w.r.t. their segment orientation estimation accuracy in the presence of model calibration errors with and without using magnetometer information. While the existing EKF-based method uses a segment-centered kinematic chain biomechanical model and a constant angular acceleration motion model, the newly developed/adapted methods are all based on a free segments model, where each segment is represented with six degrees of freedom in the global frame. Moreover, these methods differ in the assumed motion model (constant angular acceleration, constant angular velocity, inertial data as control input), the state representation (segment-centered, IMU-centered) and the estimation method (EKF, sliding window optimization). In addition to the free segments representation, the optimization-based method also represents each IMU with six degrees of freedom in the global frame. In the evaluation on simulated and real data from a three segment model (an arm), the optimization-based method showed the smallest mean errors, standard deviations and maximum errors throughout all tests. It also showed the lowest dependency on magnetometer information and motion agility. Moreover, it was insensitive w.r.t. I2S position and segment length errors in the tested ranges. Errors in the I2S orientations were, however, linearly propagated into the estimated segment orientations. In the absence of magnetic disturbances, severe model calibration errors and fast motion changes, the newly developed IMU centered EKF-based method yielded comparable results with lower computational complexity. PMID:27455266

Global trends in world fisheries: impacts on marine ecosystems and food security.

PubMed

Pauly, Daniel; Watson, Reg; Alder, Jackie

2005-01-29

This contribution, which reviews some broad trends in human history and in the history of fishing, argues that sustainability, however defined, rarely if ever occurred as a result of an explicit policy, but as result of our inability to access a major part of exploited stocks. With the development of industrial fishing, and the resulting invasion of the refuges previously provided by distance and depth, our interactions with fisheries resources have come to resemble the wars of extermination that newly arrived hunters conducted 40,000-50,000 years ago in Australia, and 11,000-13,000 years ago against large terrestrial mammals arrived in North America. These broad trends are documented here through a map of change in fish sizes, which displays characteristic declines, first in the nearshore waters of industrialized countries of the Northern Hemisphere, then spread offshore and to the Southern Hemisphere. This geographical extension met its natural limit in the late 1980s, when the catches from newly accessed stocks ceased to compensate for the collapse in areas accessed earlier, hence leading to a gradual decline of global landing. These trends affect developing countries more than the developed world, which have been able to meet the shortfall by increasing imports from developing countries. These trends, however, together with the rapid growth of farming of carnivorous fishes, which consumes other fishes suited for human consumption, have led to serious food security issues. This promotes urgency to the implementation of the remedies traditionally proposed to alleviate overfishing (reduction of overcapacity, enforcement of conservative total allowable catches, etc.), and to the implementation of non-conventional approaches, notably the re-establishment of the refuges (also known as marine reserves), which made possible the apparent sustainability of pre-industrial fisheries.

Development and Validation of a Rapid (13)C6-Glucose Isotope Dilution UPLC-MRM Mass Spectrometry Method for Use in Determining System Accuracy and Performance of Blood Glucose Monitoring Devices.

PubMed

Matsunami, Risë K; Angelides, Kimon; Engler, David A

2015-05-18

There is currently considerable discussion about the accuracy of blood glucose concentrations determined by personal blood glucose monitoring systems (BGMS). To date, the FDA has allowed new BGMS to demonstrate accuracy in reference to other glucose measurement systems that use the same or similar enzymatic-based methods to determine glucose concentration. These types of reference measurement procedures are only comparative in nature and are subject to the same potential sources of error in measurement and system perturbations as the device under evaluation. It would be ideal to have a completely orthogonal primary method that could serve as a true standard reference measurement procedure for establishing the accuracy of new BGMS. An isotope-dilution liquid chromatography/mass spectrometry (ID-UPLC-MRM) assay was developed using (13)C6-glucose as a stable isotope analogue to specifically measure glucose concentration in human plasma, and validated for use against NIST standard reference materials, and against fresh isolates of whole blood and plasma into which exogenous glucose had been spiked. Assay performance was quantified to NIST-traceable dry weight measures for both glucose and (13)C6-glucose. The newly developed assay method was shown to be rapid, highly specific, sensitive, accurate, and precise for measuring plasma glucose levels. The assay displayed sufficient dynamic range and linearity to measure across the range of both normal and diabetic blood glucose levels. Assay performance was measured to within the same uncertainty levels (<1%) as the NIST definitive method for glucose measurement in human serum. The newly developed ID UPLC-MRM assay can serve as a validated reference measurement procedure to which new BGMS can be assessed for glucose measurement performance. © 2015 Diabetes Technology Society.

Development and Validation of a Rapid 13C6-Glucose Isotope Dilution UPLC-MRM Mass Spectrometry Method for Use in Determining System Accuracy and Performance of Blood Glucose Monitoring Devices

PubMed Central

Matsunami, Risë K.; Angelides, Kimon; Engler, David A.

2015-01-01

Background: There is currently considerable discussion about the accuracy of blood glucose concentrations determined by personal blood glucose monitoring systems (BGMS). To date, the FDA has allowed new BGMS to demonstrate accuracy in reference to other glucose measurement systems that use the same or similar enzymatic-based methods to determine glucose concentration. These types of reference measurement procedures are only comparative in nature and are subject to the same potential sources of error in measurement and system perturbations as the device under evaluation. It would be ideal to have a completely orthogonal primary method that could serve as a true standard reference measurement procedure for establishing the accuracy of new BGMS. Methods: An isotope-dilution liquid chromatography/mass spectrometry (ID-UPLC-MRM) assay was developed using 13C6-glucose as a stable isotope analogue to specifically measure glucose concentration in human plasma, and validated for use against NIST standard reference materials, and against fresh isolates of whole blood and plasma into which exogenous glucose had been spiked. Assay performance was quantified to NIST-traceable dry weight measures for both glucose and 13C6-glucose. Results: The newly developed assay method was shown to be rapid, highly specific, sensitive, accurate, and precise for measuring plasma glucose levels. The assay displayed sufficient dynamic range and linearity to measure across the range of both normal and diabetic blood glucose levels. Assay performance was measured to within the same uncertainty levels (<1%) as the NIST definitive method for glucose measurement in human serum. Conclusions: The newly developed ID UPLC-MRM assay can serve as a validated reference measurement procedure to which new BGMS can be assessed for glucose measurement performance. PMID:25986627

Global trends in world fisheries: impacts on marine ecosystems and food security

PubMed Central

Pauly, Daniel; Watson, Reg; Alder, Jackie

2005-01-01

This contribution, which reviews some broad trends in human history and in the history of fishing, argues that sustainability, however defined, rarely if ever occurred as a result of an explicit policy, but as result of our inability to access a major part of exploited stocks. With the development of industrial fishing, and the resulting invasion of the refuges previously provided by distance and depth, our interactions with fisheries resources have come to resemble the wars of extermination that newly arrived hunters conducted 40 000–50 000 years ago in Australia, and 12 000–13 000 years ago against large terrestrial mammals in North America. These broad trends are documented here through a map of change in fish sizes, which displays characteristic declines, first in the nearshore waters of industrialized countries of the Northern Hemisphere, then spread offshore and to the Southern Hemisphere. This geographical extension met its natural limit in the late 1980s, when the catches from newly accessed stocks ceased to compensate for the collapse in areas accessed earlier, hence leading to a gradual decline of global landing. These trends affect developing countries more than the developed world, which have been able to meet the shortfall by increasing imports from developing countries. These trends, however, together with the rapid growth of farming of carnivorous fishes, which consumes other fishes suited for human consumption, have led to serious food security issues. This promotes urgency to the implementation of the remedies traditionally proposed to alleviate overfishing (reduction of overcapacity, enforcement of conservative total allowable catches, etc.), and to the implementation of non-conventional approaches, notably the re-establishment of the refuges (also known as marine reserves), which made possible the apparent sustainability of pre-industrial fisheries. PMID:15713585

Poly(3-hydroxybutyrate)-ethyl cellulose based bio-composites with novel characteristics for infection free wound healing application.

PubMed

Iqbal, Hafiz M N; Kyazze, Godfrey; Locke, Ian Charles; Tron, Thierry; Keshavarz, Tajalli

2015-11-01

A series of bio-composites including poly3-hydroxybutyrate [P(3HB)] grafted ethyl cellulose (EC) stated as P(3HB)-EC were successfully synthesised. Furthermore, natural phenols e.g., p-4-hydroxybenzoic acid (HBA) and ferulic acid (FA) were grafted onto the newly developed P(3HB)-EC-based bio-composites under laccase-assisted environment without the use of additional initiators or crosslinking agents. The phenol grafted bio-composites were critically evaluated for their antibacterial and biocompatibility features as well as their degradability in soil. In particular, the results of the antibacterial evaluation for the newly developed bio-composites indicated that 20HBA-g-P(3HB)-EC and 15FA-g-P(3HB)-EC bio-composites exerted strong bactericidal and bacteriostatic activity against Gram(-)E. coli NTCT 10418 as compared to the Gram(+)B. subtilis NCTC 3610. This study shows further that at various phenolic concentrations the newly synthesised bio-composites remained cytocompatible with human keratinocyte-like HaCaT skin cells, as 100% cell viability was recorded, in vitro. As for the degradation, an increase in the degradation rate was recorded during the soil burial analyses over a period of 42 days. These findings suggest that the reported bio-composites have great potential for use in wound healing; covering the affected skin area which may favour tissue repair over shorter periods. Copyright © 2015 Elsevier B.V. All rights reserved.

HIV Disease: Current Concepts.

ERIC Educational Resources Information Center

Keeling, Richard P.

1993-01-01

Describes human immunodeficiency virus (HIV), newly characterized human retrovirus which causes chronic, progressive, immune deficiency disease, the most severe phase of which is Acquired Immune Deficiency Syndrome (AIDS). Reviews most important current epidemiologic, clinical, and virologic information about HIV and HIV disease and provides…

A Mouse to Human Search for Plasma Proteome Changes Associated with Pancreatic Tumor Development

PubMed Central

Faca, Vitor M; Song, Kenneth S; Wang, Hong; Zhang, Qing; Krasnoselsky, Alexei L; Newcomb, Lisa F; Plentz, Ruben R; Gurumurthy, Sushma; Redston, Mark S; Pitteri, Sharon J; Pereira-Faca, Sandra R; Ireton, Renee C; Katayama, Hiroyuki; Glukhova, Veronika; Phanstiel, Douglas; Brenner, Dean E; Anderson, Michelle A; Misek, David; Scholler, Nathalie; Urban, Nicole D; Barnett, Matt J; Edelstein, Cim; Goodman, Gary E; Thornquist, Mark D; McIntosh, Martin W; DePinho, Ronald A; Bardeesy, Nabeel; Hanash, Samir M

2008-01-01

Background The complexity and heterogeneity of the human plasma proteome have presented significant challenges in the identification of protein changes associated with tumor development. Refined genetically engineered mouse (GEM) models of human cancer have been shown to faithfully recapitulate the molecular, biological, and clinical features of human disease. Here, we sought to exploit the merits of a well-characterized GEM model of pancreatic cancer to determine whether proteomics technologies allow identification of protein changes associated with tumor development and whether such changes are relevant to human pancreatic cancer. Methods and Findings Plasma was sampled from mice at early and advanced stages of tumor development and from matched controls. Using a proteomic approach based on extensive protein fractionation, we confidently identified 1,442 proteins that were distributed across seven orders of magnitude of abundance in plasma. Analysis of proteins chosen on the basis of increased levels in plasma from tumor-bearing mice and corroborating protein or RNA expression in tissue documented concordance in the blood from 30 newly diagnosed patients with pancreatic cancer relative to 30 control specimens. A panel of five proteins selected on the basis of their increased level at an early stage of tumor development in the mouse was tested in a blinded study in 26 humans from the CARET (Carotene and Retinol Efficacy Trial) cohort. The panel discriminated pancreatic cancer cases from matched controls in blood specimens obtained between 7 and 13 mo prior to the development of symptoms and clinical diagnosis of pancreatic cancer. Conclusions Our findings indicate that GEM models of cancer, in combination with in-depth proteomic analysis, provide a useful strategy to identify candidate markers applicable to human cancer with potential utility for early detection. PMID:18547137

Near-Earth Asteroids: Destinations for Human Exploration

NASA Technical Reports Server (NTRS)

Barbee, Brent W.

2014-01-01

The Near-Earth Object Human Space Flight Accessible Targets Study (NHATS) is a system that monitors the near-Earth asteroid (NEA) population to identify NEAs whose orbital characteristics may make them potential destinations for future round-trip human space flight missions. To accomplish this monitoring, Brent Barbee (GSFC) developed and automated a system that applies specialized trajectory processing to the orbits of newly discovered NEAs, and those for which we have updated orbit knowledge, obtained from the JPL Small Bodies Database (SBDB). This automated process executes daily and the results are distributed to the general public and the astronomy community. This aids in prioritizing telescope radar time allocations for obtaining crucial follow-up observations of highly accessible NEAs during the critical, because it is often fleeting, time period surrounding the time at which the NEAs are initially discovered.

Development of KRISS standard reference photometer (SRP) for ambient ozone measurement

NASA Astrophysics Data System (ADS)

Lee, S.; Lee, J.

2014-12-01

Surface ozone has adverse impacts on human health and ecosystem. Accurate measurement of ambient ozone concentration is essential for developing effective mitigation strategies and understanding atmospheric chemistry. Korea Research Institute of Standards and Science (KRISS) has developed new ozone standard reference photometers (SRPs) for the calibration of ambient ozone instruments. The basic principle of the KRISS ozone SRPs is to determine the absorption of ultraviolet radiation at a specific wavelength, 253.7 nm, by ozone in the atmosphere. Ozone concentration is calculated by converting UV transmittance through the Beer-Lambert Law. This study introduces the newly developed ozone SRPs and characterizes their performance through uncertainty analysis and comparison with BIPM (International Bureau of Weights and Measures) SRP.

Evaluation of a computerized aid for creating human behavioral representations of human-computer interaction.

PubMed

Williams, Kent E; Voigt, Jeffrey R

2004-01-01

The research reported herein presents the results of an empirical evaluation that focused on the accuracy and reliability of cognitive models created using a computerized tool: the cognitive analysis tool for human-computer interaction (CAT-HCI). A sample of participants, expert in interacting with a newly developed tactical display for the U.S. Army's Bradley Fighting Vehicle, individually modeled their knowledge of 4 specific tasks employing the CAT-HCI tool. Measures of the accuracy and consistency of task models created by these task domain experts using the tool were compared with task models created by a double expert. The findings indicated a high degree of consistency and accuracy between the different "single experts" in the task domain in terms of the resultant models generated using the tool. Actual or potential applications of this research include assessing human-computer interaction complexity, determining the productivity of human-computer interfaces, and analyzing an interface design to determine whether methods can be automated.

Recent Progresses in Incorporating Human Land-Water Management into Global Land Surface Models Toward Their Integration into Earth System Models

NASA Technical Reports Server (NTRS)

Pokhrel, Yadu N.; Hanasaki, Naota; Wada, Yoshihide; Kim, Hyungjun

2016-01-01

The global water cycle has been profoundly affected by human land-water management. As the changes in the water cycle on land can affect the functioning of a wide range of biophysical and biogeochemical processes of the Earth system, it is essential to represent human land-water management in Earth system models (ESMs). During the recent past, noteworthy progress has been made in large-scale modeling of human impacts on the water cycle but sufficient advancements have not yet been made in integrating the newly developed schemes into ESMs. This study reviews the progresses made in incorporating human factors in large-scale hydrological models and their integration into ESMs. The study focuses primarily on the recent advancements and existing challenges in incorporating human impacts in global land surface models (LSMs) as a way forward to the development of ESMs with humans as integral components, but a brief review of global hydrological models (GHMs) is also provided. The study begins with the general overview of human impacts on the water cycle. Then, the algorithms currently employed to represent irrigation, reservoir operation, and groundwater pumping are discussed. Next, methodological deficiencies in current modeling approaches and existing challenges are identified. Furthermore, light is shed on the sources of uncertainties associated with model parameterizations, grid resolution, and datasets used for forcing and validation. Finally, representing human land-water management in LSMs is highlighted as an important research direction toward developing integrated models using ESM frameworks for the holistic study of human-water interactions within the Earths system.

Development of a biomimetic roughness sensor for tactile information with an elastomer

NASA Astrophysics Data System (ADS)

Choi, Jae-Young; Kim, Sung Joon; Moon, Hyungpil; Choi, Hyouk Ryeol; Koo, Ja Choon

2016-04-01

Human uses various sensational information for identifying an object. When contacting an unidentified object with no vision, tactile sensation provides a variety of information to perceive. Tactile sensation plays an important role to recognize a shape of surfaces from touching. In robotic fields, tactile sensation is especially meaningful. Robots can perform more accurate job using comprehensive tactile information. And in case of using sensors made by soft material like silicone, sensors can be used in various situations. So we are developing a tactile sensor with soft materials. As the conventional robot operates in a controlled environment, it is a good model to make robots more available at any circumstance that sensory systems of living things. For example, there are lots of mechanoreceptors that each of them has different roles detecting simulation in side of human skin tissue. By mimicking the mechanoreceptor, a sensory system can be realized more closely to human being. It is known that human obtains roughness information through scanning the surface with fingertips. During that times, subcutaneous mechanoreceptors detect vibration. In the same way, while a robot is scanning a surface of object, a roughness sensor developed detects vibrations generated between contacting two surfaces. In this research, a roughness sensor made by an elastomer was developed and experiment for perception of objects was conducted. We describe means to compare the roughness of objects with a newly developed sensor.

Mountain research

NASA Astrophysics Data System (ADS)

The newly incorporated International Mountain Society (IMS) will in May begin publication of an interdisciplinary scientific journal, Mountain Research and Development. The quarterly will be copublished with the United National University; additional support will come from UNESCO.A primary objective of IMS is to ‘help solve mountain land-use problems by developing a foundation of scientific and technical knowledge on which to base management decisions,’ according to Jack D. Ives, president of the Boulder-based organization. ‘The Society is strongly committed to the belief that a rational worldwide approach to mountain problems must involve a wide range of disciplines in the natural and human sciences, medicine, architecture, engineering, and technology.’

Treatment of the femoral shaft fracture with a curved heat-treated COP clover-leaf nail.

PubMed

Onoue, Y; Sunami, Y; Fujiwara, H; Sadakane, T; Yasuda, S

1979-01-01

The commonly used straight intramedullary nail has certain limitations and disadvantages. Following radiographic and metallurgical studies we have developed a curved heat-treated clover-leaf nail using a newly developed precipitation hardening stainless steel (COP). The nail is bent with a slot on the convex side and the radius of curvature is 115 cm which corresponds to the anatomical antero-lateral convexity of the human femur. The nail has been satisfactory in clinical use since 1971 and has provided not only more stable internal fixation but also allowed fixation of fractures beyond the middle third of the shaft.

Mi-DISCOVERER: A bioinformatics tool for the detection of mi-RNA in human genome.

PubMed

Arshad, Saadia; Mumtaz, Asia; Ahmad, Freed; Liaquat, Sadia; Nadeem, Shahid; Mehboob, Shahid; Afzal, Muhammad

2010-11-27

MicroRNAs (miRNAs) are 22 nucleotides non-coding RNAs that play pivotal regulatory roles in diverse organisms including the humans and are difficult to be identified due to lack of either sequence features or robust algorithms to efficiently identify. Therefore, we made a tool that is Mi-Discoverer for the detection of miRNAs in human genome. The tools used for the development of software are Microsoft Office Access 2003, the JDK version 1.6.0, BioJava version 1.0, and the NetBeans IDE version 6.0. All already made miRNAs softwares were web based; so the advantage of our project was to make a desktop facility to the user for sequence alignment search with already identified miRNAs of human genome present in the database. The user can also insert and update the newly discovered human miRNA in the database. Mi-Discoverer, a bioinformatics tool successfully identifies human miRNAs based on multiple sequence alignment searches. It's a non redundant database containing a large collection of publicly available human miRNAs.

Mi-DISCOVERER: A bioinformatics tool for the detection of mi-RNA in human genome

PubMed Central

Arshad, Saadia; Mumtaz, Asia; Ahmad, Freed; Liaquat, Sadia; Nadeem, Shahid; Mehboob, Shahid; Afzal, Muhammad

2010-01-01

MicroRNAs (miRNAs) are 22 nucleotides non-coding RNAs that play pivotal regulatory roles in diverse organisms including the humans and are difficult to be identified due to lack of either sequence features or robust algorithms to efficiently identify. Therefore, we made a tool that is Mi-Discoverer for the detection of miRNAs in human genome. The tools used for the development of software are Microsoft Office Access 2003, the JDK version 1.6.0, BioJava version 1.0, and the NetBeans IDE version 6.0. All already made miRNAs softwares were web based; so the advantage of our project was to make a desktop facility to the user for sequence alignment search with already identified miRNAs of human genome present in the database. The user can also insert and update the newly discovered human miRNA in the database. Mi-Discoverer, a bioinformatics tool successfully identifies human miRNAs based on multiple sequence alignment searches. It's a non redundant database containing a large collection of publicly available human miRNAs. PMID:21364831

Combination of in situ metathesis reaction with a novel "magnetic effervescent tablet-assisted ionic liquid dispersive microextraction" for the determination of endogenous steroids in human fluids.

PubMed

Wu, Jia; Xu, Zilin; Pan, Yixuan; Shi, Yi; Bao, Xiujie; Li, Jun; Tong, Yu; Tang, Han; Ma, Shuyan; Wang, Xuedong; Lyu, Jianxin

2018-05-01

Herein, a novel magnetic effervescence tablet-assisted microextraction coupled to in situ metathesis reaction of ionic liquid (IS-META-ILDM) is presented for the determination of four endogenous steroids in human urine, pregnant women's blood, and fetal umbilical cord blood. The magnetic effervescent tablets, which were composed of Fe 3 O 4 nanoparticles, sodium carbonate (alkaline source), and tartaric acid (acidic source), were used to disperse the extractant and for convenient magnetic separation. After the effervescent reaction, in situ reaction between NH 4 PF 6 and [C 6 MIM]BF 4 was adopted to change hydrophilic ionic liquid to hydrophobic liquid, which could be separated from the aqueous phase. The newly developed method has three obvious advantages: (1) combination of effervescent dispersion and magnetic nanoparticles' retrieval is cost-effective and the dispersion and collection of the extractant can be completed almost simultaneously; (2) as compared to temperature-controlled ionic liquid dispersive microextraction and cold-induced solidified microextraction, this method avoids a heating and cooling process which significantly reduces the extraction time and energy cost; and (3) the combination of adsorption by magnetic nanoparticles with extraction by in situ metathesis reaction easily produces high recoveries for target analytes. The optimized composition of effervescent tablet and experimental parameters are as follows: 0.64 g mixture of sodium carbonate and tartaric acid, 7 mg of Fe 3 O 4 (20 nm) as magnetic sorbents, 40 μL of [C 6 MIM]BF 4 as the extraction solvent, 0.15 g NH 4 PF 6 , and 300 μL of elution solvent. Under the optimized conditions, the newly developed method provided high extraction recoveries (90.0-118.5%) and low LODs (0.14-0.17 μg L -1 ) in urine and blood samples. In total, this IS-META-ILDM method provided high extraction efficiency, fast and convenient separation, and underutilization of any organic solvent, and thus it has great potential for the determination of trace endogenous steroids in complex human fluids. Graphical abstract The newly developed method has three obvious advantages: combination of effervescent dispersion and magnetic nanoparticles' retrieval is cost-effective and the dispersion and collection of the extractant can be completed almost simultaneously. It avoids a heating and cooling process which significantly reduces the extraction time and energy cost and easily produces high recoveries for target analytes.

Differential Pathological and Immune Responses in Newly Weaned Ferrets Are Associated with a Mild Clinical Outcome of Pandemic 2009 H1N1 Infection

PubMed Central

Huang, Stephen S. H.; Banner, David; Degousee, Norbert; Leon, Alberto J.; Xu, Louling; Paquette, Stephane G.; Kanagasabai, Thirumagal; Fang, Yuan; Rubino, Salvatore; Rubin, Barry; Kelvin, Alyson A.

2012-01-01

Young children are typically considered a high-risk group for disease associated with influenza virus infection. Interestingly, recent clinical reports suggested that young children were the smallest group of cases with severe pandemic 2009 H1N1 (H1N1pdm) influenza virus infection. Here we established a newly weaned ferret model for the investigation of H1N1pdm infection in young age groups compared to adults. We found that young ferrets had a significantly milder fever and less weight loss than adult ferrets, which paralleled the mild clinical symptoms in the younger humans. Although there was no significant difference in viral clearance, disease severity was associated with pulmonary pathology, where newly weaned ferrets had an earlier pathology improvement. We examined the immune responses associated with protection of the young age group during H1N1pdm infection. We found that interferon and regulatory interleukin-10 responses were more robust in the lungs of young ferrets. In contrast, myeloperoxidase and major histocompatibility complex responses were persistently higher in the adult lungs; as well, the numbers of inflammation-prone granulocytes were highly elevated in the adult peripheral blood. Importantly, we observed that H1N1pdm infection triggered formation of lung structures that resembled inducible bronchus-associated lymphoid tissues (iBALTs) in young ferrets which were associated with high levels of homeostatic chemokines CCL19 and CXCL13, but these were not seen in the adult ferrets with severe disease. These results may be extrapolated to a model of the mild disease seen in human children. Furthermore, these mechanistic analyses provide significant new insight into the developing immune system and effective strategies for intervention and vaccination against respiratory viruses. PMID:23055557

Differential pathological and immune responses in newly weaned ferrets are associated with a mild clinical outcome of pandemic 2009 H1N1 infection.

PubMed

Huang, Stephen S H; Banner, David; Degousee, Norbert; Leon, Alberto J; Xu, Louling; Paquette, Stephane G; Kanagasabai, Thirumagal; Fang, Yuan; Rubino, Salvatore; Rubin, Barry; Kelvin, David J; Kelvin, Alyson A

2012-12-01

Young children are typically considered a high-risk group for disease associated with influenza virus infection. Interestingly, recent clinical reports suggested that young children were the smallest group of cases with severe pandemic 2009 H1N1 (H1N1pdm) influenza virus infection. Here we established a newly weaned ferret model for the investigation of H1N1pdm infection in young age groups compared to adults. We found that young ferrets had a significantly milder fever and less weight loss than adult ferrets, which paralleled the mild clinical symptoms in the younger humans. Although there was no significant difference in viral clearance, disease severity was associated with pulmonary pathology, where newly weaned ferrets had an earlier pathology improvement. We examined the immune responses associated with protection of the young age group during H1N1pdm infection. We found that interferon and regulatory interleukin-10 responses were more robust in the lungs of young ferrets. In contrast, myeloperoxidase and major histocompatibility complex responses were persistently higher in the adult lungs; as well, the numbers of inflammation-prone granulocytes were highly elevated in the adult peripheral blood. Importantly, we observed that H1N1pdm infection triggered formation of lung structures that resembled inducible bronchus-associated lymphoid tissues (iBALTs) in young ferrets which were associated with high levels of homeostatic chemokines CCL19 and CXCL13, but these were not seen in the adult ferrets with severe disease. These results may be extrapolated to a model of the mild disease seen in human children. Furthermore, these mechanistic analyses provide significant new insight into the developing immune system and effective strategies for intervention and vaccination against respiratory viruses.

Cell-Free, De Nova Synthesis of Poliovirus

NASA Astrophysics Data System (ADS)

Molla, Akhteruzzaman; Paul, Aniko V.; Wimmer, Eckard

1991-12-01

Cell-free translation of poliovirus RNA in an extract of uninfected human (HeLa) cells yielded viral proteins through proteolysis of the polyprotein. In the extract, newly synthesized proteins catalyzed poliovirus-specific RNA synthesis, and formed infectious poliovirus de novo. Newly formed virions were neutralized by type-specific antiserum, and infection of human cells with them was prevented by poliovirus receptor-specific antibodies. Poliovirus synthesis was increased nearly 70-fold when nucleoside triphosphates were added, but it was abolished in the presence of inhibitors of translation or viral genome replication. The ability to conduct cell-free synthesis of poliovirus will aid in the study of picornavirus proliferation and in the search for the control of picornaviral disease.

Use of optical skin phantoms for preclinical evaluation of laser efficiency for skin lesion therapy

PubMed Central

Wróbel, Maciej S.; Jędrzejewska-Szczerska, Malgorzata; Galla, Stanislaw; Piechowski, Leszek; Sawczak, Miroslaw; Popov, Alexey P.; Bykov, Alexander V.; Tuchin, Valery V.; Cenian, Adam

2015-01-01

Abstract. Skin lesions are commonly treated using laser heating. However, the introduction of new devices into clinical practice requires evaluation of their performance. This study presents the application of optical phantoms for assessment of a newly developed 975-nm pulsed diode laser system for dermatological purposes. Such phantoms closely mimic the absorption and scattering of real human skin (although not precisely in relation to thermal conductivity and capacitance); thus, they can be used as substitutes for human skin for approximate evaluation of laser heating efficiency in an almost real environment. Thermographic imaging was applied to measure the spatial and temporal temperature distributions on the surface of laser-irradiated phantoms. The study yielded results of heating with regard to phantom thickness and absorption, as well as laser settings. The methodology developed can be used in practice for preclinical evaluations of laser treatment for dermatology. PMID:26263414

Second generation codon optimized minicircle (CoMiC) for nonviral reprogramming of human adult fibroblasts.

PubMed

Diecke, Sebastian; Lisowski, Leszek; Kooreman, Nigel G; Wu, Joseph C

2014-01-01

The ability to induce pluripotency in somatic cells is one of the most important scientific achievements in the fields of stem cell research and regenerative medicine. This technique allows researchers to obtain pluripotent stem cells without the controversial use of embryos, providing a novel and powerful tool for disease modeling and drug screening approaches. However, using viruses for the delivery of reprogramming genes and transcription factors may result in integration into the host genome and cause random mutations within the target cell, thus limiting the use of these cells for downstream applications. To overcome this limitation, various non-integrating techniques, including Sendai virus, mRNA, minicircle, and plasmid-based methods, have recently been developed. Utilizing a newly developed codon optimized 4-in-1 minicircle (CoMiC), we were able to reprogram human adult fibroblasts using chemically defined media and without the need for feeder cells.

LZ-207, a Newly Synthesized Flavonoid, Induces Apoptosis and Suppresses Inflammation-Related Colon Cancer by Inhibiting the NF-κB Signaling Pathway.

PubMed

Sun, Jie; Li, Fanni; Zhao, Yue; Zhao, Li; Qiao, Chen; Li, Zhiyu; Guo, Qinglong; Lu, Na

2015-01-01

Flavonoids and flavonoid derivatives, which have significant biological and pharmacological activities, including antitumor and anti-inflammatory activities, have been widely used in human healthcare. To design a more effective flavonoid antitumor agent, we altered the flavonoid backbone with substitutions of piperazine and methoxy groups to synthesize a novel flavonoid derivative, LZ-207. The anticancer effect of LZ-207 against HCT116 colon cancer cells and the underlying mechanism of this effect were explored in this study. Specifically, LZ-207 exhibited inhibitory effects on growth and viability in several human colon cancer cell lines and induced apoptosis in HCT116 cells both in vitro and in vivo. LZ-207 treatment also suppressed the nuclear translocation of NF-κB and the phosphorylation of IκB and IKKα/β in a dose-dependent manner in both HCT116 cells and human acute monocytic leukemia THP-1 cells. Moreover, LZ-207 also reduced the secretion of the pro-inflammatory cytokine interleukin-6 (IL-6) in LPS-induced THP-1 cells, and this effect was confirmed at the transcriptional level. Furthermore, LZ-207 significantly inhibited HCT116 cell proliferation that was elicited by LPS-induced THP-1 cells in a co-culture system. These findings elucidated some potential molecular mechanisms for preventing inflammation-driven colon cancer using the newly synthesized flavonoid LZ-207 and suggested the possibility of further developing novel therapeutic agents derived from flavonoids.

Environmental Transport of Emerging Human-Pathogenic Cryptosporidium Species and Subtypes through Combined Sewer Overflow and Wastewater

PubMed Central

Huang, Chengchen; Hu, Yue; Wang, Lin; Wang, Yuanfei; Li, Na; Guo, Yaqiong; Xiao, Lihua

2017-01-01

ABSTRACT The environmental transport of Cryptosporidium spp. through combined sewer overflow (CSO) and the occurrence of several emerging human-pathogenic Cryptosporidium species in developing countries remain unclear. In this study, we collected 40 CSO samples and 40 raw wastewater samples from Shanghai, China, and examined them by PCR and DNA sequencing for Cryptosporidium species (targeting the small subunit rRNA gene) and Giardia duodenalis (targeting the triosephosphate isomerase, β-giardin, and glutamate dehydrogenase genes) and Enterocytozoon bieneusi (targeting the ribosomal internal transcribed spacer) genotypes. Human-pathogenic Cryptosporidium species were further subtyped by sequence analysis of the 60-kDa glycoprotein gene, with additional multilocus sequence typing on the emerging zoonotic pathogen Cryptosporidium ubiquitum. Cryptosporidium spp., G. duodenalis, and E. bieneusi were detected in 12 and 15, 33 and 32, and 37 and 40 CSO and wastewater samples, respectively, including 10 Cryptosporidium species, 3 G. duodenalis assemblages, and 8 E. bieneusi genotypes. In addition to Cryptosporidium hominis and Cryptosporidium parvum, two new pathogens identified in industrialized nations, C. ubiquitum and Cryptosporidium viatorum, were frequently detected. The two novel C. ubiquitum subtype families identified appeared to be genetic recombinants of known subtype families. Similarly, the dominant group 1 E. bieneusi genotypes and G. duodenalis subassemblage AII are known human pathogens. The similar distribution of human-pathogenic Cryptosporidium species and E. bieneusi and G. duodenalis genotypes between wastewater and CSO samples reaffirms that storm overflow is potentially a significant contamination source of pathogens in surface water. The frequent identification of C. ubiquitum and C. viatorum in urban wastewater suggests that these newly identified human pathogens may be endemic in China. IMPORTANCE Cryptosporidium spp., Giardia duodenalis, and Enterocytozoon bieneusi are major waterborne pathogens. Their transport into surface water through combined sewer overflow, which remains largely untreated in developing countries, has not been examined. In addition, the identification of these pathogens to genotypes and subtypes in urban storm overflow and wastewater is necessary for rapid and accurate assessment of pathogen transmission in humans and transport in the environment. Data from this study suggest that, like untreated urban wastewater, combined sewer overflow is commonly contaminated with human-pathogenic Cryptosporidium, G. duodenalis, and E. bieneusi genotypes and subtypes, and urban storm overflow potentially plays a significant role in the contamination of drinking source water and recreational water with human pathogens. They also indicate that Cryptosporidium ubiquitum and Cryptosporidium viatorum, two newly identified human pathogens, may be common in China, and genetic recombination can lead to the emergence of novel C. ubiquitum subtype families. PMID:28600310

The Visual System of Zebrafish and its Use to Model Human Ocular Diseases

PubMed Central

Gestri, Gaia; Link, Brian A; Neuhauss, Stephan CF

2011-01-01

Free swimming zebrafish larvae depend mainly on their sense of vision to evade predation and to catch prey. Hence there is strong selective pressure on the fast maturation of visual function and indeed the visual system already supports a number of visually-driven behaviors in the newly hatched larvae. The ability to exploit the genetic and embryonic accessibility of the zebrafish in combination with a behavioral assessment of visual system function has made the zebrafish a popular model to study vision and its diseases. Here, we review the anatomy, physiology and development of the zebrafish eye as the basis to relate the contributions of the zebrafish to our understanding of human ocular diseases. PMID:21595048

Development and Function of the Human Fetal Adrenal Cortex: A Key Component in the Feto-Placental Unit

PubMed Central

Ishimoto, Hitoshi

2011-01-01

Continuous efforts have been devoted to unraveling the biophysiology and development of the human fetal adrenal cortex, which is structurally and functionally unique from other species. It plays a pivotal role, mainly through steroidogenesis, in the regulation of intrauterine homeostasis and in fetal development and maturation. The steroidogenic activity is characterized by early transient cortisol biosynthesis, followed by its suppressed synthesis until late gestation, and extensive production of dehydroepiandrosterone and its sulfate, precursors of placental estrogen, during most of gestation. The gland rapidly grows through processes including cell proliferation and angiogenesis at the gland periphery, cellular migration, hypertrophy, and apoptosis. Recent studies employing modern technologies such as gene expression profiling and laser capture microdissection have revealed that development and/or function of the fetal adrenal cortex may be regulated by a panoply of molecules, including transcription factors, extracellular matrix components, locally produced growth factors, and placenta-derived CRH, in addition to the primary regulator, fetal pituitary ACTH. The role of the fetal adrenal cortex in human pregnancy and parturition appears highly complex, probably due to redundant and compensatory mechanisms regulating these events. Mounting evidence indicates that actions of hormones operating in the human feto-placental unit are likely mediated by mechanisms including target tissue responsiveness, local metabolism, and bioavailability, rather than changes only in circulating levels. Comprehensive study of such molecular mechanisms and the newly identified factors implicated in adrenal development should help crystallize our understanding of the development and physiology of the human fetal adrenal cortex. PMID:21051591

Expression signatures of early-stage and advanced medaka melanomas.

PubMed

Klotz, Barbara; Kneitz, Susanne; Regensburger, Martina; Hahn, Lena; Dannemann, Michael; Kelso, Janet; Nickel, Birgit; Lu, Yuan; Boswell, William; Postlethwait, John; Warren, Wesley; Kunz, Manfred; Walter, Ronald B; Schartl, Manfred

2018-06-01

Melanoma is one of the most aggressive tumors with a very low survival rate once metastasized. The incidence of newly detected cases increases every year suggesting the necessity of development and application of innovative treatment strategies. Human melanoma develops from melanocytes localized in the epidermis of the skin to malignant tumors because of deregulated effectors influencing several molecular pathways. Despite many advances in describing the molecular changes accompanying melanoma formation, many critical and clinically relevant molecular features of the transformed pigment cells and the underlying mechanisms are largely unknown. To contribute to a better understanding of the molecular processes of melanoma formation, we use a transgenic medaka melanoma model that is well suited for the investigation of melanoma tumor development because fish and human melanocytes are both localized in the epidermis. The purpose of our study was to gain insights into melanoma development from the first steps of tumor formation up to melanoma progression and to identify gene expression patterns that will be useful for monitoring treatment effects in drug screening approaches. Comparing transcriptomes from juvenile fish at the tumor initiating stage with nevi and advanced melanoma of adults, we identified stage specific expression signatures and pathways that are characteristic for the development of medaka melanoma, and are also found in human malignancies. Copyright © 2017 Elsevier Inc. All rights reserved.

Reduced acquisition and reactivation of human papillomavirus infections among older women treated with cryotherapy: results from a randomized trial in South Africa.

PubMed

Taylor, Sylvia; Wang, Chunhui; Wright, Thomas C; Denny, Lynette; Tsai, Wei-Yann; Kuhn, Louise

2010-06-29

Treatment of women for high-grade cervical cancer precursors frequently results in clearance of the associated high-risk human papillomavirus (hrHPV) infection but the role of treatment among women without hrHPV is unknown. We investigated whether cervical cryotherapy reduces newly detected hrHPV infections among HIV-positive and HIV-negative women who were hrHPV negative when treated. The impact of cryotherapy on newly detected hrHPV infections was examined among 612 women of known HIV serostatus, aged 35 to 65 years, who were negative for hrHPV DNA, and randomized to either undergo cryotherapy (n = 309) or not (n = 303). All women underwent repeat hrHPV DNA testing 6, 12, 24, and 36 months later. Among 540 HIV-negative women, cryotherapy was associated with a significant reduction in newly detected hrHPV infections. Women in the cryotherapy group were 55% less likely to have newly detected hrHPV than women in the control group (95% CI 0.28 to 0.71). This association was independent of the influence of changes in sexual behaviors following therapy (adjusted hazards ratio (HR) = 0.49, 95% CI 0.29 to 0.81). Among 72 HIV-positive women, similar reductions were not observed (HR = 1.10, 95% CI 0.53 to 2.29). Cervical cryotherapy significantly reduced newly detected hrHPV infections among HIV-negative, but not HIV-positive women. These results raise intriguing questions about immunological responses and biological mechanisms underlying the apparent prophylactic benefits of cryotherapy.

Reduced acquisition and reactivation of human papillomavirus infections among older women treated with cryotherapy: results from a randomized trial in South Africa

PubMed Central

2010-01-01

Background Treatment of women for high-grade cervical cancer precursors frequently results in clearance of the associated high-risk human papillomavirus (hrHPV) infection but the role of treatment among women without hrHPV is unknown. We investigated whether cervical cryotherapy reduces newly detected hrHPV infections among HIV-positive and HIV-negative women who were hrHPV negative when treated. Methods The impact of cryotherapy on newly detected hrHPV infections was examined among 612 women of known HIV serostatus, aged 35 to 65 years, who were negative for hrHPV DNA, and randomized to either undergo cryotherapy (n = 309) or not (n = 303). All women underwent repeat hrHPV DNA testing 6, 12, 24, and 36 months later. Results Among 540 HIV-negative women, cryotherapy was associated with a significant reduction in newly detected hrHPV infections. Women in the cryotherapy group were 55% less likely to have newly detected hrHPV than women in the control group (95% CI 0.28 to 0.71). This association was independent of the influence of changes in sexual behaviors following therapy (adjusted hazards ratio (HR) = 0.49, 95% CI 0.29 to 0.81). Among 72 HIV-positive women, similar reductions were not observed (HR = 1.10, 95% CI 0.53 to 2.29). Conclusions Cervical cryotherapy significantly reduced newly detected hrHPV infections among HIV-negative, but not HIV-positive women. These results raise intriguing questions about immunological responses and biological mechanisms underlying the apparent prophylactic benefits of cryotherapy. PMID:20587028

Professor Joseph Warren Horton (1889-1967): biological engineer.

PubMed

Zeitlin, Gerald L

2005-02-01

Joseph Warren Horton graduated with a degree in electrical engineering from the Massachusetts Institute of Technology (MIT) in 1914. He became involved in the early development of electrical measurement devices, televised image transmission, and the detection of underwater sound transmission. In the mid-1930s he was appointed the first leader of the newly created Department of Biological Engineering at MIT and in this position he made major contributions to the application of physics to human physiology, in particular by increasing the safety of explosive inhalational anaesthetic agents.

Development of a reconstructed cornea from collagen-chondroitin sulfate foams and human cell cultures.

PubMed

Vrana, N Engin; Builles, Nicolas; Justin, Virginie; Bednarz, Jurgen; Pellegrini, Graziella; Ferrari, Barbara; Damour, Odile; Hulmes, David J S; Hasirci, Vasif

2008-12-01

To develop an artificial cornea, the ability to coculture the different cell types present in the cornea is essential. Here the goal was to develop a full-thickness artificial cornea using an optimized collagen-chondroitin sulfate foam, with a thickness close to that of human cornea, by coculturing human corneal epithelial and stromal cells and transfected human endothelial cells. Corneal extracellular matrix was simulated by a porous collagen/glycosaminoglycan-based scaffold seeded with stromal keratocytes and then, successively, epithelial and endothelial cells. Scaffolds were characterized for bulk porosity and pore size distribution. The performance of the three-dimensional construct was studied by histology, immunofluorescence, and immunohistochemistry. The scaffold had 85% porosity and an average pore size of 62.1 microm. Keratocytes populated the scaffold and produced a newly synthesized extracellular matrix as characterized by immunohistochemistry. Even though the keratocytes lost their CD34 phenotype marker, the absence of smooth muscle actin fibers showed that these cells had not differentiated into myofibroblasts. The epithelial cells formed a stratified epithelium and began basement membrane deposition. An endothelial cell monolayer beneath the foam was also apparent. These results demonstrate that collagen-chondroitin sulfate scaffolds are good substrates for artificial cornea construction with good resilience, long-term culture capability, and handling properties.

Field Performance of a Newly Developed Upflow Filtration Device

EPA Science Inventory

The objective of this research is to examine the removal capacities of a newly developed Upflow filtration device for treatment of stormwater. The device was developed by engineers at the University of Alabama through a Small Business Innovative Research (SBIR) grant from the U....

The Near-Earth Object Human Space Flight Accessible Targets Study (NHATS) List of Near-Earth Asteroids: Identifying Potential Targets for Future Exploration

NASA Technical Reports Server (NTRS)

Abell, Paul A.; Barbee, B. W.; Mink, R. G.; Alberding, C. M.; Adamo, D. R.; Mazanek, D. D.; Johnson, L. N.; Yeomans, D. K.; Chodas, P. W.; Chamberlin, A. B.;

Repair of calvarial bone defects in mice using electrospun polystyrene scaffolds combined with β-TCP or gold nanoparticles.

PubMed

Terranova, Lisa; Dragusin, Diana Maria; Mallet, Romain; Vasile, Eugeniu; Stancu, Izabela-Cristina; Behets, Catherine; Chappard, Daniel

2017-02-01

Non-biodegradable porous polystyrene (PS) scaffolds, composed of microfibers, have been prepared by electrospinning for the reconstruction of large bone defects. PS microfibers were prepared by incorporating β-TCP grains inside the polymer or grafting gold nanoparticles surface functionalized with mercaptosuccinic acid. Cytocompatibility of the three types of scaffolds (PS, β-TCP-PS and Au-PS) was studied by seeding human mesenchymal stem cells. Biocompatibility was evaluated by implanting β-TCP-PS and Au-PS scaffolds into a critical size (4mm) calvarial defect in mice. Calvaria were taken 6, 9, and 12 weeks after implantation; newly formed bone and cellular response was analyzed by microcomputed tomography (microCT) and histology. β-TCP-PS scaffolds showed a significantly higher cell proliferation in vitro than on PS or Au-PS alone; clearly, the presence of β-TCP grains improved cytocompatibility. Biocompatibility study in the mouse calvaria model showed that β-TCP-PS scaffolds were significantly associated with more newly-formed bone than Au-PS. Bone developed by osteoconduction from the defect margins to the center. A dense fibrous connective tissue containing blood vessels was identified histologically in both types of scaffolds. There was no inflammatory foci nor giant cell in these areas. AuNPs aggregates were identified histologically in the fibrosis and also incorporated in the newly-formed bone matrix. Although the different types of PS microfibers appeared cytocompatible during the in vitro experiment, they appeared biotolerated in vivo since they induced a fibrotic reaction associated with newly formed bone. Copyright © 2016 Elsevier Ltd. All rights reserved.

Assessing College Students' Perceptions of a Case Teacher's Pedagogical Content Knowledge Using a Newly Developed Instrument

ERIC Educational Resources Information Center

Jang, Syh-Jong

2011-01-01

Ongoing professional development for college teachers has been much emphasized. However, previous research on learning environments has seldom addressed college students' perceptions of teachers' PCK. This study aimed to evaluate college students' perceptions of a physics teacher's PCK development using a newly developed instrument and workshop…

Preparing School Leaders: The Professional Development Needs of Newly Appointed Principals

ERIC Educational Resources Information Center

Ng, Shun-wing; Szeto, Sing-ying Elson

2016-01-01

In Hong Kong, there is an acute need to provide newly appointed principals with opportunities for continuous professional development so that they could face the impact of reforms and globalization on school development. The Education Bureau has commissioned the tertiary institutions to provide structured professional development courses to cater…

Nickel-free austenitic stainless steels for medical applications.

PubMed

Yang, Ke; Ren, Yibin

2010-02-01

The adverse effects of nickel ions being released into the human body have prompted the development of high-nitrogen nickel-free austenitic stainless steels for medical applications. Nitrogen not only replaces nickel for austenitic structure stability but also much improves steel properties. Here we review the harmful effects associated with nickel in medical stainless steels, the advantages of nitrogen in stainless steels, and emphatically, the development of high-nitrogen nickel-free stainless steels for medical applications. By combining the benefits of stable austenitic structure, high strength and good plasticity, better corrosion and wear resistances, and superior biocompatibility compared to the currently used 316L stainless steel, the newly developed high-nitrogen nickel-free stainless steel is a reliable substitute for the conventional medical stainless steels.

Nickel-free austenitic stainless steels for medical applications

PubMed Central

Yang, Ke; Ren, Yibin

2010-01-01

The adverse effects of nickel ions being released into the human body have prompted the development of high-nitrogen nickel-free austenitic stainless steels for medical applications. Nitrogen not only replaces nickel for austenitic structure stability but also much improves steel properties. Here we review the harmful effects associated with nickel in medical stainless steels, the advantages of nitrogen in stainless steels, and emphatically, the development of high-nitrogen nickel-free stainless steels for medical applications. By combining the benefits of stable austenitic structure, high strength and good plasticity, better corrosion and wear resistances, and superior biocompatibility compared to the currently used 316L stainless steel, the newly developed high-nitrogen nickel-free stainless steel is a reliable substitute for the conventional medical stainless steels. PMID:27877320

Selection of unadapted, pathogenic SHIVs encoding newly transmitted HIV-1 envelope proteins.

PubMed

Del Prete, Gregory Q; Ailers, Braiden; Moldt, Brian; Keele, Brandon F; Estes, Jacob D; Rodriguez, Anthony; Sampias, Marissa; Oswald, Kelli; Fast, Randy; Trubey, Charles M; Chertova, Elena; Smedley, Jeremy; LaBranche, Celia C; Montefiori, David C; Burton, Dennis R; Shaw, George M; Markowitz, Marty; Piatak, Michael; KewalRamani, Vineet N; Bieniasz, Paul D; Lifson, Jeffrey D; Hatziioannou, Theodora

2014-09-10

Infection of macaques with chimeric viruses based on SIVMAC but expressing the HIV-1 envelope (Env) glycoproteins (SHIVs) remains the most powerful model for evaluating prevention and therapeutic strategies against AIDS. Unfortunately, only a few SHIVs are currently available. Furthermore, their generation has required extensive adaptation of the HIV-1 Env sequences in macaques so they may not accurately represent HIV-1 Env proteins circulating in humans, potentially limiting their translational utility. We developed a strategy for generating large numbers of SHIV constructs expressing Env proteins from newly transmitted HIV-1 strains. By inoculating macaques with cocktails of multiple SHIV variants, we selected SHIVs that can replicate and cause AIDS-like disease in immunologically intact rhesus macaques without requiring animal-to-animal passage. One of these SHIVs could be transmitted mucosally. We demonstrate the utility of the SHIVs generated by this method for evaluating neutralizing antibody administration as a protection against mucosal SHIV challenge. Copyright © 2014 Elsevier Inc. All rights reserved.

Phylodynamics and Human-Mediated Dispersal of a Zoonotic Virus

PubMed Central

Talbi, Chiraz; Lemey, Philippe; Suchard, Marc A.; Abdelatif, Elbia; Elharrak, Mehdi; Jalal, Nourlil; Faouzi, Abdellah; Echevarría, Juan E.; Vazquez Morón, Sonia; Rambaut, Andrew; Campiz, Nicholas; Tatem, Andrew J.; Holmes, Edward C.; Bourhy, Hervé

2010-01-01

Understanding the role of humans in the dispersal of predominately animal pathogens is essential for their control. We used newly developed Bayesian phylogeographic methods to unravel the dynamics and determinants of the spread of dog rabies virus (RABV) in North Africa. Each of the countries studied exhibited largely disconnected spatial dynamics with major geo-political boundaries acting as barriers to gene flow. Road distances proved to be better predictors of the movement of dog RABV than accessibility or raw geographical distance, with occasional long distance and rapid spread within each of these countries. Using simulations that bridge phylodynamics and spatial epidemiology, we demonstrate that the contemporary viral distribution extends beyond that expected for RABV transmission in African dog populations. These results are strongly supportive of human-mediated dispersal, and demonstrate how an integrated phylogeographic approach will turn viral genetic data into a powerful asset for characterizing, predicting, and potentially controlling the spatial spread of pathogens. PMID:21060816

[Energy saving and LED lamp lighting and human health].

PubMed

Deĭnego, V N; Kaptsov, V A

2013-01-01

The appearance of new sources of high-intensity with large proportion of blue light in the spectrum revealed new risks of their influence on the function of the eye and human health, especially for children and teenagers. There is an urgent need to reconsider the research methods of vision hygiene in conditions of energy-saving and LED bulbs lighting. On the basis of a systematic approach and knowledge of the newly discovered photosensitive receptors there was built hierarchical model of the interaction of "light environment - the eye - the system of formation of visual images - the hormonal system of the person - his psycho-physiological state." This approach allowed us to develop a range of risk for the negative impact of spectrum on the functions of the eye and human health, as well as to formulate the hygiene requirements for energy-efficient high-intensity light sources.

Morphological identification of animal hairs: Myths and misconceptions, possibilities and pitfalls.

PubMed

Tridico, S R; Houck, M M; Kirkbride, K Paul; Smith, M E; Yates, B C

2014-05-01

The examination of hair collected from crime scenes is an important and highly informative discipline relevant to many forensic investigations. However, the forensic identification of animal (non-human) hairs requires different skill sets and competencies to those required for human hair comparisons. The aim of this is paper is not only to highlight the intrinsic differences between forensic human hair comparison and forensic animal hair identification, but also discuss the utility and reliability of the two in the context of possibilities and pitfalls. It also addresses and dispels some of the more popular myths and misconceptions surrounding the microscopical examination of animal hairs. Furthermore, future directions of this discipline are explored through the proposal of recommendations for minimum standards for the morphological identification of animal hairs and the significance of the newly developed guidelines by SWGWILD is discussed. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Quasi-static modeling of human limb for intra-body communications with experiments.

PubMed

Pun, Sio Hang; Gao, Yue Ming; Mak, PengUn; Vai, Mang I; Du, Min

2011-11-01

In recent years, the increasing number of wearable devices on human has been witnessed as a trend. These devices can serve for many purposes: personal entertainment, communication, emergency mission, health care supervision, delivery, etc. Sharing information among the devices scattered across the human body requires a body area network (BAN) and body sensor network (BSN). However, implementation of the BAN/BSN with the conventional wireless technologies cannot give optimal result. It is mainly because the high requirements of light weight, miniature, energy efficiency, security, and less electromagnetic interference greatly limit the resources available for the communication modules. The newly developed intra-body communication (IBC) can alleviate most of the mentioned problems. This technique, which employs the human body as a communication channel, could be an innovative networking method for sensors and devices on the human body. In order to encourage the research and development of the IBC, the authors are favorable to lay a better and more formal theoretical foundation on IBC. They propose a multilayer mathematical model using volume conductor theory for galvanic coupling IBC on a human limb with consideration on the inhomogeneous properties of human tissue. By introducing and checking with quasi-static approximation criteria, Maxwell's equations are decoupled and capacitance effect is included to the governing equation for further improvement. Finally, the accuracy and potential of the model are examined from both in vitro and in vivo experimental results.

Key role of staff competencies for patient and donor safety in a bone marrow transplantation unit: design and implementation of an accredited training and self-assessment program.

PubMed

Lamanna, C; Baroni, M; Bisin, S; Gianassi, S; Bambi, F; Caselli, D; Aricò, M

2010-01-01

Human resources represent at the moment the most critical factor in an hospital setting characterized by a high rate of staff turnover. It is important to ensure a consistent level of expertise and knowledge of professionals who work in health care facilities to provide quality services and simultaneously support the implementation of strategies for patient safety. Unfortunately, the development of effective interventions for training newly added staff and self-evaluation of skills possessed by trained staff are closely related to understanding critical aspects of the organization. At the new Center for Bone Marrow Transplantation and Blood Transfusion Service in Meyer Hospital, during the last year, a group of professional nurses and technicians completed a specific plan to train new staff and, at the same time, a program of self-assessment of skills for experienced staff. The main purpose of this project was to promote skills development by newly added as well as experienced staff, to identify areas of weaknesses, and to correct them with training (organized by the hospital, departmental, or individual) designed to improve performance. Copyright 2010 Elsevier Inc. All rights reserved.

Genetic Mapping of Resistance to Meloidogyne arenaria in Arachis stenosperma: A New Source of Nematode Resistance for Peanut

PubMed Central

Leal-Bertioli, Soraya C. M.; Moretzsohn, Márcio C.; Roberts, Philip A.; Ballén-Taborda, Carolina; Borba, Tereza C. O.; Valdisser, Paula A.; Vianello, Rosana P.; Araújo, Ana Cláudia G; Guimarães, Patricia M.; Bertioli, David J.

2015-01-01

Root-knot nematodes (RKN; Meloidogyne sp.) are a major threat to crops in tropical and subtropical regions worldwide. The use of resistant crop varieties is the preferred method of control because nematicides are expensive, and hazardous to humans and the environment. Peanut (Arachis hypogaea) is infected by four species of RKN, the most damaging being M. arenaria, and commercial cultivars rely on a single source of resistance. In this study, we genetically characterize RKN resistance of the wild Arachis species A. stenosperma using a population of 93 recombinant inbred lines developed from a cross between A. duranensis and A. stenosperma. Four quantitative trait loci (QTL) located on linkage groups 02, 04, and 09 strongly influenced nematode root galling and egg production. Drought-related, domestication and agronomically relevant traits were also evaluated, revealing several QTL. Using the newly available Arachis genome sequence, easy-to-use KASP (kompetitive allele specific PCR) markers linked to the newly identified RKN resistance loci were developed and validated in a tetraploid context. Therefore, we consider that A. stenosperma has high potential as a new source of RKN resistance in peanut breeding programs. PMID:26656152

Fluorescence properties of human teeth and dental calculus for clinical applications

NASA Astrophysics Data System (ADS)

Lee, Yong-Keun

2015-04-01

Fluorescent emission of human teeth and dental calculus is important for the esthetic rehabilitation of teeth, diagnosis of dental caries, and detection of dental calculus. The purposes of this review were to summarize the fluorescence and phosphorescence of human teeth by ambient ultraviolet (UV) light, to investigate the clinically relevant fluorescence measurement methods in dentistry, and to review the fluorescence of teeth and dental calculus by specific wavelength light. Dentine was three times more phosphorescent than enamel. When exposed to light sources containing UV components, the fluorescence of human teeth gives them the quality of vitality, and fluorescent emission with a peak of 440 nm is observed. Esthetic restorative materials should have fluorescence properties similar to those of natural teeth. Based on the fluorescence of teeth and restorative materials as determined with a spectrophotometer, a fluorescence parameter was defined. As to the fluorescence spectra by a specific wavelength, varied wavelengths were investigated for clinical applications, and several methods for the diagnosis of dental caries and the detection of dental calculus were developed. Since fluorescent properties of dental hard tissues have been used and would be expanded in diverse fields of clinical practice, these properties should be investigated further, embracing newly developed optical techniques.

Fluorescence properties of human teeth and dental calculus for clinical applications.

PubMed

Lee, Yong-Keun

2015-04-01

Fluorescent emission of human teeth and dental calculus is important for the esthetic rehabilitation of teeth, diagnosis of dental caries, and detection of dental calculus. The purposes of this review were to summarize the fluorescence and phosphorescence of human teeth by ambient ultraviolet (UV) light, to investigate the clinically relevant fluorescence measurement methods in dentistry, and to review the fluorescence of teeth and dental calculus by specific wavelength light. Dentine was three times more phosphorescent than enamel. When exposed to light sources containing UV components, the fluorescence of human teeth gives them the quality of vitality, and fluorescent emission with a peak of 440 nm is observed. Esthetic restorative materials should have fluorescence properties similar to those of natural teeth. Based on the fluorescence of teeth and restorative materials as determined with a spectrophotometer, a fluorescence parameter was defined. As to the fluorescence spectra by a specific wavelength, varied wavelengths were investigated for clinical applications, and several methods for the diagnosis of dental caries and the detection of dental calculus were developed. Since fluorescent properties of dental hard tissues have been used and would be expanded in diverse fields of clinical practice, these properties should be investigated further, embracing newly developed optical techniques.

Challenges and advances in mouse modeling for human pancreatic tumorigenesis and metastasis

PubMed Central

Qiu, Wanglong

2013-01-01

Pancreatic cancer is critical for developed countries, where its rate of diagnosis has been increasing steadily annually. In the past decade, the advances of pancreatic cancer research have not contributed to the decline in mortality rates from pancreatic cancer—the overall 5-year survival rate remains about 5% low. This number only underscores an obvious urgency for us to better understand the biological features of pancreatic carcinogenesis, to develop early detection methods, and to improve novel therapeutic treatments. To achieve these goals, animal modeling that faithfully recapitulates the whole process of human pancreatic cancer is central to making the advancements. In this review, we summarize the currently available animal models for pancreatic cancer and the advances in pancreatic cancer animal modeling. We compare and contrast the advantages and disadvantages of three major categories of these models: (1) carcinogen-induced; (2) xenograft and allograft; and (3) genetically engineered mouse models. We focus more on the genetically engineered mouse models, a category which has been rapidly expanded recently for their capacities to mimic human pancreatic cancer and metastasis, and highlight the combinations of these models with various newly developed strategies and cell-lineage labeling systems. PMID:23114842

Ultrasonographic monitoring of fetal development in unrestrained bonobos (Pan paniscus) at the Milwaukee County Zoo.

PubMed

Drews, Barbara; Harmann, Leanne M; Beehler, Leann L; Bell, Barbara; Drews, Reinhard F; Hildebrandt, Thomas B

2011-01-01

The bonobo, Pan paniscus, is one of the most endangered primate species. In the context of the Bonobo Species Survival Plan(®), the Milwaukee County Zoo established a successful breeding group. Although the bonobo serves as a model species for human evolution, no prenatal growth curves are available. To develop growth graphs, the animals at the Milwaukee County Zoo were trained by positive reinforcement to allow for ultrasound exams without restraint. With this method, the well being of mother and fetus were maintained and ultrasound exams could be performed frequently. The ovulation date of the four animals in the study was determined exactly so that gestational age was known for each examination. Measurements of biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC), and femur length (FL) were used to create growth curves. Prenatal growth of P. paniscus was compared with the data of humans and the common chimpanzee, P. troglodytes. With respect to cranial structures, such as BPD and HC, humans have significant acceleration of growth compared with P. paniscus and P. troglodytes. In P. paniscus, growth of AC was similar to HC throughout pregnancy, whereas in humans AC only reaches the level of HC close to term. Growth rate of FL was similar in humans and the two Pan species until near day 180 post-ovulation. After that, the Pan species FL growth slowed compared with human FL. The newly developed fetal growth curves of P. paniscus will assist in monitoring prenatal development and predicting birth dates of this highly endangered species. © 2010 Wiley-Liss, Inc.

Intrinsically Disordered Protein Specific Force Field CHARMM36IDPSFF.

PubMed

Liu, Hao; Song, Dong; Lu, Hui; Luo, Ray; Chen, Hai-Feng

2018-05-28

Intrinsically disordered proteins (IDPs) are closely related to various human diseases. Because IDPs lack certain tertiary structure, it is difficult to use X-ray and NMR methods to measure their structures. Therefore, molecular dynamics simulation is a useful tool to study the conformer distribution of IDPs. However, most generic protein force fields were found to be insufficient in simulations of IDPs. Here we report our development for the CHARMM community. Our residue-specific IDP force field (CHARMM36IDPSFF) was developed based on the base generic force field with CMAP corrections of for all 20 naturally occurring amino acids. Multiple tests show that the simulated chemical shifts with the newly developed force field are in quantitative agreement with NMR experiment and are more accurate than the base generic force field. Comparison of J-couplings with previous work shows that CHARMM36IDPSFF and its corresponding base generic force field have their own advantages. In addition, CHARMM36IDPSFF simulations also agree with experiment for SAXS profiles and radii of gyration of IDPs. Detailed analysis shows that CHARMM36IDPSFF can sample more diverse and disordered conformers. These findings confirm that the newly developed force field can improve the balance of accuracy and efficiency for the conformer sampling of IDPs. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

PROGRESS REPORT ON THE DSSTOX DATABASE NETWORK: NEWLY LAUNCHED WEBSITE, APPLICATIONS, FUTURE PLANS

EPA Science Inventory

Progress Report on the DSSTox Database Network: Newly Launched Website, Applications, Future Plans

Progress will be reported on development of the Distributed Structure-Searchable Toxicity (DSSTox) Database Network and the newly launched public website that coordinates and...

Regulation of VH Replacement by B Cell Receptor (BCR)-mediated Signaling in Human Immature B Cells

PubMed Central

Liu, Jing; Lange, Miles D.; Hong, Sang Yong; Xie, Wanqin; Xu, Kerui; Huang, Lin; Yu, Yangsheng; Ehrhardt, Götz R. A.; Zemlin, Michael; Burrows, Peter D.; Su, Kaihong; Carter, Robert H.; Zhang, Zhixin

2013-01-01

VH replacement provides a unique RAG-mediated recombination mechanism to edit non-functional IgH genes or IgH genes encoding self reactive B cell receptors (BCRs) and contributes to the diversification of antibody repertoire in mouse and human. Currently, it is not clear how VH replacement is regulated during early B lineage cell development. Here we show that crosslinking BCRs induces VH replacement in human EU12 μHC+ cells and in the newly emigrated immature B cells purified from peripheral blood of healthy donors or tonsillar samples. BCR signaling-induced VH replacement is dependent on the activation of Syk and Src kinases; but is inhibited by CD19 co-stimulation, presumably through activation of the PI3 kinase pathway. These results show for the first time that VH replacement is regulated by BCR-mediated signaling in human immature B cells, which can be modulated by physiological and pharmacological treatments. PMID:23630348

Impacts of Encouraging Dog Walking on Returns of Newly Adopted Dogs to a Shelter.

PubMed

Gunter, Lisa; Protopopova, Alexandra; Hooker, Steven P; Der Ananian, Cheryl; Wynne, Clive D L

2017-01-01

This study involved examining the ability of a postadoption intervention to reduce returns of newly adopted dogs to shelters by encouraging physical activity between adopters and their dogs. Guardians in the intervention group received emails with dog behavior and human activity advice as well as invitations to join weekly dog walks. Both the intervention and control groups completed surveys regarding outdoor activity with their dogs, their dog-walking habits, and perceptions of their dogs' behaviors. Adopter-dog pairs in the intervention group were not significantly more active than those in the control group, nor did they show a reduced incidence of returning their dogs. Guardians in both groups who reported higher obligation and self-efficacy in their dog walking were more active regardless of experimental condition; however, obligation, dog-walking self-efficacy, and perceptions about their dogs' on-leash behaviors did not predict rates of return to the shelter. These findings add to the understanding of shelter dog re-relinquishment and the effective utilization of resources postadoption, and they indicate further research is needed to address the complexities of this newly forming human-dog relationship.

Children's Concepts of How People Get Babies

ERIC Educational Resources Information Center

Bernstein, Anne C.; Cowan, Philip A.

1975-01-01

Twenty children, 3-12 years old, were given a newly constructed interview on their concepts of human reproduction (social causality), in conjunction with Piaget-type tasks assessing physical conservation-identity, physical causality, and a new social identity task. The children's concepts of human reproduction appeared to proceed through a…

DNA Data Bank of Japan (DDBJ) for genome scale research in life science

PubMed Central

Tateno, Y.; Imanishi, T.; Miyazaki, S.; Fukami-Kobayashi, K.; Saitou, N.; Sugawara, H.; Gojobori, T.

2002-01-01

The DNA Data Bank of Japan (DDBJ, http://www.ddbj.nig.ac.jp) has made an effort to collect as much data as possible mainly from Japanese researchers. The increase rates of the data we collected, annotated and released to the public in the past year are 43% for the number of entries and 52% for the number of bases. The increase rates are accelerated even after the human genome was sequenced, because sequencing technology has been remarkably advanced and simplified, and research in life science has been shifted from the gene scale to the genome scale. In addition, we have developed the Genome Information Broker (GIB, http://gib.genes.nig.ac.jp) that now includes more than 50 complete microbial genome and Arabidopsis genome data. We have also developed a database of the human genome, the Human Genomics Studio (HGS, http://studio.nig.ac.jp). HGS provides one with a set of sequences being as continuous as possible in any one of the 24 chromosomes. Both GIB and HGS have been updated incorporating newly available data and retrieval tools. PMID:11752245

Adaptive Optical System for Retina Imaging Approaches Clinic Applications

NASA Astrophysics Data System (ADS)

Ling, N.; Zhang, Y.; Rao, X.; Wang, C.; Hu, Y.; Jiang, W.; Jiang, C.

We presented "A small adaptive optical system on table for human retinal imaging" at the 3rd Workshop on Adaptive Optics for Industry and Medicine. In this system, a 19 element small deformable mirror was used as wavefront correction element. High resolution images of photo receptors and capillaries of human retina were obtained. In recent two years, at the base of this system a new adaptive optical system for human retina imaging has been developed. The wavefront correction element is a newly developed 37 element deformable mirror. Some modifications have been adopted for easy operation. Experiments for different imaging wavelengths and axial positions were conducted. Mosaic pictures of photoreceptors and capillaries were obtained. 100 normal and abnormal eyes of different ages have been inspected.The first report in the world concerning the most detailed capillary distribution images cover ±3° by ± 3° field around the fovea has been demonstrated. Some preliminary very early diagnosis experiment has been tried in laboratory. This system is being planned to move to the hospital for clinic experiments.

In vivo cell biology in zebrafish - providing insights into vertebrate development and disease.

PubMed

Vacaru, Ana M; Unlu, Gokhan; Spitzner, Marie; Mione, Marina; Knapik, Ela W; Sadler, Kirsten C

2014-02-01

Over the past decades, studies using zebrafish have significantly advanced our understanding of the cellular basis for development and human diseases. Zebrafish have rapidly developing transparent embryos that allow comprehensive imaging of embryogenesis combined with powerful genetic approaches. However, forward genetic screens in zebrafish have generated unanticipated findings that are mirrored by human genetic studies: disruption of genes implicated in basic cellular processes, such as protein secretion or cytoskeletal dynamics, causes discrete developmental or disease phenotypes. This is surprising because many processes that were assumed to be fundamental to the function and survival of all cell types appear instead to be regulated by cell-specific mechanisms. Such discoveries are facilitated by experiments in whole animals, where zebrafish provides an ideal model for visualization and manipulation of organelles and cellular processes in a live vertebrate. Here, we review well-characterized mutants and newly developed tools that underscore this notion. We focus on the secretory pathway and microtubule-based trafficking as illustrative examples of how studying cell biology in vivo using zebrafish has broadened our understanding of the role fundamental cellular processes play in embryogenesis and disease.

Mapping subsurface in proximity to newly-developed sinkhole along roadway.

DOT National Transportation Integrated Search

2013-02-01

MS&T acquired electrical resistivity tomography profiles in immediate proximity to a newly-developed sinkhole in Nixa Missouri : The sinkhole has closed a well-traveled municipal roadway and threatens proximal infrastructure. The intent of this inves...

Comparison of UTCI to selected thermal indices.

PubMed

Blazejczyk, Krzysztof; Epstein, Yoram; Jendritzky, Gerd; Staiger, Henning; Tinz, Birger

2012-05-01

Over the past century more than 100 indices have been developed and used to assess bioclimatic conditions for human beings. The majority of these indices are used sporadically or for specific purposes. Some are based on generalized results of measurements (wind chill, cooling power, wet bulb temperature) and some on the empirically observed reactions of the human body to thermal stress (physiological strain, effective temperature). Those indices that are based on human heat balance considerations are referred to as "rational indices". Several simple human heat balance models are known and are used in research and practice. This paper presents a comparative analysis of the newly developed Universal Thermal Climate Index (UTCI), and some of the more prevalent thermal indices. The analysis is based on three groups of data: global data-set, synoptic datasets from Europe, and local scale data from special measurement campaigns of COST Action 730. We found the present indices to express bioclimatic conditions reasonably only under specific meteorological situations, while the UTCI represents specific climates, weather, and locations much better. Furthermore, similar to the human body, the UTCI is very sensitive to changes in ambient stimuli: temperature, solar radiation, wind and humidity. UTCI depicts temporal variability of thermal conditions better than other indices. The UTCI scale is able to express even slight differences in the intensity of meteorological stimuli.

A fetal human heart cardiac-inducing RNA (CIR) promotes the differentiation of stem cells into cardiomyocytes.

PubMed

Kochegarov, Andrei; Moses-Arms, Ashley; Lemanski, Larry F

2015-08-01

A specific human fetal heart RNA has been discovered, which has the ability to induce myocardial cell formation from mouse embryonic and human-induced pluripotent stem cells in culture. In this study, commercially obtained RNA from human fetal heart was cloned, sequenced, and synthesized using standard laboratory approaches. Molecular analyses of the specific fetal cardiac-inducing RNA (CIR), revealed that it is a fragment of N-sulfoglucosaminesulfohydrolase and the caspase recruitment domain family member 14 precursor. Stem cells transfected with CIRs often form into spindle-shaped cells characteristic of cardiomyocytes,and express the cardiac-specific contractile protein marker, troponin-T, in addition to tropomyosin and α-actinin as detected by immunohistochemical staining. Expression of these contractile proteins showed organization into sarcomeric myofibrils characteristic of striated cardiac muscle cells. Computer analyses of the RNA secondary structures of the active CIR show significant similarities to a RNA from salamander or myofibril-inducing RNA (MIR), which also promotes non-muscle cells to differentiate into cardiac muscle. Thus, these two RNAs, salamander MIR and the newly discovered human-cloned CIR reported here, appear to have evolutionarily conserved secondary structures suggesting that both play major roles in vertebrate heart development and, particularly, in the differentiation of cardiomyocytes from non-muscle cells during development.

Fraud and abuse. Building an effective corporate compliance program.

PubMed

Matusicky, C F

1998-04-01

In 1997, General Health System (GHS), a not-for-profit integrated delivery system headquartered in Baton Rouge, Louisiana, developed a formal corporate compliance program. A newly appointed corporate compliance officer worked with key GHS managers and employees to assess the organization's current fraud and abuse prevention practices and recommend changes to meet new regulatory and organizational requirements. Then a structure for implementing these changes was developed, with staff training at its core. The program required a significant initial outlay of financial and human resources. The benefits to the organization, however, including a greater ability to respond quickly and effectively to possible compliance problems and better organizational communications, were worth the investment.

Targeting iron metabolism in drug discovery and delivery

PubMed Central

Crielaard, Bart J.; Lammers, Twan; Rivella, Stefano

2017-01-01

Iron fulfils a central role in many essential biochemical processes in human physiology, which makes proper processing of iron crucial. Although iron metabolism is subject to relatively strict physiological control, in recent years numerous disorders, such as cancer and neurodegenerative diseases, have been linked to deregulated iron homeostasis. Because of its involvement in the pathogenesis of these diseases, iron metabolism constitutes a promising and largely unexploited therapeutic target for the development of new pharmacological treatments. Several iron metabolism-targeted therapies are already under clinical evaluation for haematological disorders, and these and newly developed therapeutic agents will likely have substantial benefit in the clinical management of iron metabolism-associated diseases, for which few efficacious treatments are often available. PMID:28154410

Continuous All-Sky Cloud Measurements: Cloud Fraction Analysis Based on a Newly Developed Instrument

NASA Astrophysics Data System (ADS)

Aebi, C.; Groebner, J.; Kaempfer, N.; Vuilleumier, L.

2017-12-01

Clouds play an important role in the climate system and are also a crucial parameter for the Earth's surface energy budget. Ground-based measurements of clouds provide data in a high temporal resolution in order to quantify its influence on radiation. The newly developed all-sky cloud camera at PMOD/WRC in Davos (Switzerland), the infrared cloud camera (IRCCAM), is a microbolometer sensitive in the 8 - 14 μm wavelength range. To get all-sky information the camera is located on top of a frame looking downward on a spherical gold-plated mirror. The IRCCAM has been measuring continuously (day and nighttime) with a time resolution of one minute in Davos since September 2015. To assess the performance of the IRCCAM, two different visible all-sky cameras (Mobotix Q24M and Schreder VIS-J1006), which can only operate during daytime, are installed in Davos. All three camera systems have different software for calculating fractional cloud coverage from images. Our study analyzes mainly the fractional cloud coverage of the IRCCAM and compares it with the fractional cloud coverage calculated from the two visible cameras. Preliminary results of the measurement accuracy of the IRCCAM compared to the visible camera indicate that 78 % of the data are within ± 1 octa and even 93 % within ± 2 octas. An uncertainty of 1-2 octas corresponds to the measurement uncertainty of human observers. Therefore, the IRCCAM shows similar performance in detection of cloud coverage as the visible cameras and the human observers, with the advantage that continuous measurements with high temporal resolution are possible.

Spontaneous onset and transplant models of the Vk*MYC mouse show immunological sequelae comparable to human multiple myeloma.

PubMed

Cooke, Rachel E; Gherardin, Nicholas A; Harrison, Simon J; Quach, Hang; Godfrey, Dale I; Prince, Miles; Koldej, Rachel; Ritchie, David S

2016-09-06

The Vk*MYC transgenic and transplant mouse models of multiple myeloma (MM) are well established as a research tool for anti-myeloma drug discovery. However, little is known of the immune response in these models. Understanding the immunological relevance of these models is of increasing importance as immunotherapeutic drugs are developed against MM. We set out to examine how cellular immunity is affected in Vk*MYC mouse models and compare that to the immunology of patients with newly diagnosed and relapsed/refractory MM. We found that there were significant immunological responses in mice developing either spontaneous (transgenic) or transplanted MM as a consequence of the degree of tumor burden. Particularly striking were the profound B cell lymphopenia and the expansion of CD8(+) effector memory T cells within the lymphocyte population that progressively developed with advancing disease burden, mirroring changes seen in human MM. High disease burden was also associated with increased inflammatory cytokine production by T lymphocytes, which is more fitting with relapsed/refractory MM in humans. These findings have important implications for the application of this mouse model in the development of MM immunotherapies. Trial registration LitVacc ANZCTR trial ID ACTRN12613000344796; RevLite ANZCTR trial ID NCT00482261.

Evaluation of new binders using newly developed fracture energy test.

DOT National Transportation Integrated Search

2013-07-01

This study evaluated a total of seven asphalt binders with various additives : using the newly developed binder fracture energy test. The researchers prepared and : tested PAV-aged and RTFO-plus-PAV-aged specimens. This study confirmed previous : res...

13 CFR 120.812 - Probationary period for newly certified CDCs.

Code of Federal Regulations, 2013 CFR

2013-01-01

... certified CDCs. 120.812 Section 120.812 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION BUSINESS LOANS Development Company Loan Program (504) Certification Procedures to Become A Cdc § 120.812 Probationary period for newly certified CDCs. (a) Newly certified CDCs will be on probation for a period of two...

13 CFR 120.812 - Probationary period for newly certified CDCs.

Code of Federal Regulations, 2014 CFR

2014-01-01

... certified CDCs. 120.812 Section 120.812 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION BUSINESS LOANS Development Company Loan Program (504) Certification Procedures to Become A Cdc § 120.812 Probationary period for newly certified CDCs. (a) Newly certified CDCs will be on probation for a period of two...

13 CFR 120.812 - Probationary period for newly certified CDCs.

Code of Federal Regulations, 2012 CFR

2012-01-01

... certified CDCs. 120.812 Section 120.812 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION BUSINESS LOANS Development Company Loan Program (504) Certification Procedures to Become A Cdc § 120.812 Probationary period for newly certified CDCs. (a) Newly certified CDCs will be on probation for a period of two...

13 CFR 120.812 - Probationary period for newly certified CDCs.

Code of Federal Regulations, 2011 CFR

2011-01-01

... certified CDCs. 120.812 Section 120.812 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION BUSINESS LOANS Development Company Loan Program (504) Certification Procedures to Become A Cdc § 120.812 Probationary period for newly certified CDCs. (a) Newly certified CDCs will be on probation for a period of two...

Construction and Validation of an Instrument Measuring Attitudes towards Human Rights of Liberal Studies Teachers in Hong Kong

ERIC Educational Resources Information Center

Lo, Yan Lam; Leung, Yan Wing; Chow, Joseph

2015-01-01

In 2009, Liberal Studies, which can be used as a platform for human rights education, was newly introduced as a compulsory subject for the senior secondary students in Hong Kong. As teacher's attitudes impact students' learning largely, a survey was conducted in 2010 to measure Liberal Studies teachers' attitudes towards human rights. This article…

Insect-specific viruses and their potential impact on arbovirus transmission

PubMed Central

Vasilakis, Nikos; Tesh, Robert B.

2015-01-01

Arthropod-borne viruses (arboviruses) are the causative agents of significant morbidity and mortality among humans and animals globally. In the last few years, the widespread adoption of next generation sequencing and metagenomics has led to a new era of virus discovery, where many novel viruses have been documented, exhibiting a restricted host-range in mosquitoes. They represent a wide-range of insect-specific viruses within the families of Bunyaviridae, Flaviviridae, Mesoniviridae, Reoviridae, Rhabdoviridae, Togaviridae, and the newly recognized taxon of Negeviruses. Collectively, their discovery has opened new vistas about the extent of viral diversity and evolution, their influence on vector competence and ability of their insect hosts to transmit human pathogens (e.g. arboviruses), and their potential development as biological control agents or novel vaccine platforms. PMID:26322695

Human Skin 3D Bioprinting Using Scaffold-Free Approach.

PubMed

Pourchet, Léa J; Thepot, Amélie; Albouy, Marion; Courtial, Edwin J; Boher, Aurélie; Blum, Loïc J; Marquette, Christophe A

2017-02-01

Organ in vitro synthesis is one of the last bottlenecks between tissue engineering and transplantation of synthetic organs. Bioprinting has proven its capacity to produce 3D objects composed of living cells but highly organized tissues such as full thickness skin (dermis + epidermis) are rarely attained. The focus of the present study is to demonstrate the capability of a newly developed ink formulation and the use of an open source printer, for the production of a really complete skin model. Proofs are given through immunostaining and electronic microscopy that the bioprinted skin presents all characteristics of human skin, both at the molecular and macromolecular level. Finally, the printability of large skin objects is demonstrated with the printing of an adult-size ear. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Global Bathymetry: Machine Learning for Data Editing

NASA Astrophysics Data System (ADS)

Sandwell, D. T.; Tea, B.; Freund, Y.

2017-12-01

The accuracy of global bathymetry depends primarily on the coverage and accuracy of the sounding data and secondarily on the depth predicted from gravity. A main focus of our research is to add newly-available data to the global compilation. Most data sources have 1-12% of erroneous soundings caused by a wide array of blunders and measurement errors. Over the years we have hand-edited this data using undergraduate employees at UCSD (440 million soundings at 500 m resolution). We are developing a machine learning approach to refine the flagging of the older soundings and provide automated editing of newly-acquired soundings. The approach has three main steps: 1) Combine the sounding data with additional information that may inform the machine learning algorithm. The additional parameters include: depth predicted from gravity; distance to the nearest sounding from other cruises; seafloor age; spreading rate; sediment thickness; and vertical gravity gradient. 2) Use available edit decisions as training data sets for a boosted tree algorithm with a binary logistic objective function and L2 regularization. Initial results with poor quality single beam soundings show that the automated algorithm matches the hand-edited data 89% of the time. The results show that most of the information for detecting outliers comes from predicted depth with secondary contributions from distance to the nearest sounding and longitude. A similar analysis using very high quality multibeam data shows that the automated algorithm matches the hand-edited data 93% of the time. Again, most of the information for detecting outliers comes from predicted depth secondary contributions from distance to the nearest sounding and longitude. 3) The third step in the process is to use the machine learning parameters, derived from the training data, to edit 12 million newly acquired single beam sounding data provided by the National Geospatial-Intelligence Agency. The output of the learning algorithm will be confidence ratedindicating which edits the algorithm is confident on and which it is not confident. We expect the majority ( 90%) of edits to be confident and not require human intervention. Human intervention will be required only on the 10% unconfident decisions, thus reducing the amount of human work by a factor of 10 or more.

Transcriptional Changes in Schistosoma mansoni during Early Schistosomula Development and in the Presence of Erythrocytes

PubMed Central

Gobert, Geoffrey N.; Tran, Mai H.; Moertel, Luke; Mulvenna, Jason; Jones, Malcolm K.; McManus, Donald P.; Loukas, Alex

2010-01-01

Background Schistosomes cause more mortality and morbidity than any other human helminth, but control primarily relies on a single drug that kills adult worms. The newly transformed schistosomulum stage is susceptible to the immune response and is a target for vaccine development and rational drug design. Methodology/Principal Findings To identify genes which are up-regulated during the maturation of Schistosoma mansoni schistosomula in vitro, we cultured newly transformed parasites for 3 h or 5 days with and without erythrocytes and compared their transcriptional profiles using cDNA microarrays. The most apparent changes were in the up-regulation of genes between 3 h and 5 day schistosomula involved in blood feeding, tegument and cytoskeletal development, cell adhesion, and stress responses. The most highly up-regulated genes included a tegument tetraspanin Sm-tsp-3 (1,600-fold up-regulation), a protein kinase, a novel serine protease and serine protease inhibitor, and intestinal proteases belonging to distinct mechanistic classes. The inclusion of erythrocytes in the culture medium resulted in a general but less pronounced increase in transcriptional activity, with the highest up-regulation of genes involved in iron metabolism, proteolysis, and transport of fatty acids and sugars. Conclusions We have identified the genes that are up-regulated during the first 5 days of schistosomula development in vitro. Using a combination of gene silencing techniques and murine protection studies, some of these highly up-regulated transcripts can be targeted for future development of new vaccines and drugs. PMID:20161728

In vitro cytotoxicity testing of 30 reference chemicals to predict acute human and animal toxicity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Barile, F.A.; Arjun, S.; Borges, L.

1991-03-11

This study was conducted in cooperation with the Scandinavian Society of Cell Toxicology, as part of the Multicenter Evaluation for In Vitro Cytotoxicity (MEIC), and was designed to develop an in vitro model for predicting acute human and animal toxicity. The technique relies on the ability of cultured transformed rat lung epithelial cells (L2) to incorporate radiolabled amino acids into newly synthesized proteins in the absence or presence of increasing doses of the test chemical, during a 24-hr incubation. IC50 values were extrapolated from the dose-response curves after linear regression analysis. Human toxic blood concentrations estimated from rodent LD50 valuesmore » suggest that our experimental IC50's are in close correlation with the former. Validation of the data by the MEIC committee shows that our IC50 values predicted human lethal dosage as efficient as rodent LD50's. It is anticipated that this and related procedures may supplement or replace currently used animal protocols for predicting human toxicity.« less

VH Replacement Footprint Analyzer-I, a Java-Based Computer Program for Analyses of Immunoglobulin Heavy Chain Genes and Potential VH Replacement Products in Human and Mouse

PubMed Central

Huang, Lin; Lange, Miles D.; Zhang, Zhixin

2014-01-01

VH replacement occurs through RAG-mediated secondary recombination between a rearranged VH gene and an upstream unrearranged VH gene. Due to the location of the cryptic recombination signal sequence (cRSS, TACTGTG) at the 3′ end of VH gene coding region, a short stretch of nucleotides from the previous rearranged VH gene can be retained in the newly formed VH–DH junction as a “footprint” of VH replacement. Such footprints can be used as markers to identify Ig heavy chain (IgH) genes potentially generated through VH replacement. To explore the contribution of VH replacement products to the antibody repertoire, we developed a Java-based computer program, VH replacement footprint analyzer-I (VHRFA-I), to analyze published or newly obtained IgH genes from human or mouse. The VHRFA-1 program has multiple functional modules: it first uses service provided by the IMGT/V-QUEST program to assign potential VH, DH, and JH germline genes; then, it searches for VH replacement footprint motifs within the VH–DH junction (N1) regions of IgH gene sequences to identify potential VH replacement products; it can also analyze the frequencies of VH replacement products in correlation with publications, keywords, or VH, DH, and JH gene usages, and mutation status; it can further analyze the amino acid usages encoded by the identified VH replacement footprints. In summary, this program provides a useful computation tool for exploring the biological significance of VH replacement products in human and mouse. PMID:24575092

Leaf area and photosynthesis of newly emerged trifoliolate leaves are regulated by mature leaves in soybean.

PubMed

Wu, Yushan; Gong, Wanzhuo; Wang, Yangmei; Yong, Taiwen; Yang, Feng; Liu, Weigui; Wu, Xiaoling; Du, Junbo; Shu, Kai; Liu, Jiang; Liu, Chunyan; Yang, Wenyu

2018-03-29

Leaf anatomy and the stomatal development of developing leaves of plants have been shown to be regulated by the same light environment as that of mature leaves, but no report has yet been written on whether such a long-distance signal from mature leaves regulates the total leaf area of newly emerged leaves. To explore this question, we created an investigation in which we collected data on the leaf area, leaf mass per area (LMA), leaf anatomy, cell size, cell number, gas exchange and soluble sugar content of leaves from three soybean varieties grown under full sunlight (NS), shaded mature leaves (MS) or whole plants grown in shade (WS). Our results show that MS or WS cause a marked decline both in leaf area and LMA in newly developing leaves. Leaf anatomy also showed characteristics of shade leaves with decreased leaf thickness, palisade tissue thickness, sponge tissue thickness, cell size and cell numbers. In addition, in the MS and WS treatments, newly developed leaves exhibited lower net photosynthetic rate (Pn), stomatal conductance (Gs) and transpiration rate (E), but higher carbon dioxide (CO 2 ) concentration in the intercellular space (Ci) than plants grown in full sunlight. Moreover, soluble sugar content was significantly decreased in newly developed leaves in MS and WS treatments. These results clearly indicate that (1) leaf area, leaf anatomical structure, and photosynthetic function of newly developing leaves are regulated by a systemic irradiance signal from mature leaves; (2) decreased cell size and cell number are the major cause of smaller and thinner leaves in shade; and (3) sugars could possibly act as candidate signal substances to regulate leaf area systemically.

Broad diversity and newly cultured bacterial isolates from enrichment of pig feces on complex polysaccharides

USDA-ARS?s Scientific Manuscript database

Microbial fermentation of plant cell wall components to short chain fatty acids in the large intestine provides energy to both humans and pigs. To better understand plant cell wall fermentation in the pig and human intestine, we isolated cellulose, xylan, and pectin fermenting bacteria from pig and ...

Immanuel Kant's Account of Cognitive Experience and Human Rights Education

ERIC Educational Resources Information Center

Bynum, Gregory Lewis

2012-01-01

In this essay Gregory Bynum seeks to show that Immanuel Kant's thought, which was conceived in an eighteenth-century context of new, and newly widespread, pressures for nationally institutionalized human rights-based regimes (the American and French revolutions being the most prominent examples), can help us think in new and appreciative ways…

6,6″-Dimethyl-2,2':6',2″-terpyridine revisited: new fluorescent silver(I) helicates with in vitro antiproliferative activity via selective nucleoli targeting.

PubMed

Fik, Marta A; Gorczyński, Adam; Kubicki, Maciej; Hnatejko, Zbigniew; Fedoruk-Wyszomirska, Agnieszka; Wyszko, Eliza; Giel-Pietraszuk, Małgorzata; Patroniak, Violetta

2014-10-30

6,6″-Dimethyl-2,2':6',2″-terpyridine ligand (L) reacts in equimolar ratio with Ag(I) ions what results in formation of dinuclear double helicates, which differ in terms of framework and complexity in accordance to counterions and solvent applied. Obtained complexes were thoroughly studied in terms of their biological activity, with the positive antiproliferative outcome on three human cancer cell lines: human breast cancer (T47D), human cervical carcinoma (HeLa) and human lung cancer (A-549). Performed DNA binding experiments showed that given Ag(I) species specifically interact with DNA double helix via intercalation and were visualized by confocal microscopy to specifically bind to the nuclei. All newly synthesized helical systems exhibit promising antimicrobial activity against Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus bacterial strains. Spectrophotometric properties were described as fulfilment of structural studies of newly presented complexes confirming their helical structure in solution. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Apolipoprotein A5: A newly identified gene impacting plasmatriglyceride levels in humans and mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pennacchio, Len A.; Rubin, Edward M.

2002-09-15

Apolipoprotein A5 (APOA5) is a newly described member of theapolipoprotein gene family whose initial discovery arose from comparativesequence analysis of the mammalian APOA1/C3/A4 gene cluster. Functionalstudies in mice indicated that alteration in the level of APOA5significantly impacted plasma triglyceride concentrations. Miceover-expressing human APOA5 displayed significantly reducedtriglycerides, while mice lacking apoA5 had a large increase in thislipid parameter. Studies in humans have also suggested an important rolefor APOA5 in determining plasma triglyceride concentrations. In theseexperiments, polymorphisms in the human gene were found to define severalcommon haplotypes that were associated with significant changes intriglyceride concentrations in multiple populations. Several separateclinical studies havemore » provided consistent and strong support for theeffect with 24 percent of Caucasians, 35 percent of African-Americans and53 percent of Hispanics carrying APOA5 haplotypes associated withincreased plasma triglyceride levels. In summary, APOA5 represents anewly discovered gene involved in triglyceride metabolism in both humansand mice whose mechanism of action remains to be deciphered.« less

Genetic determinants of freckle occurrence in the Spanish population: Towards ephelides prediction from human DNA samples.

PubMed

Hernando, Barbara; Ibañez, Maria Victoria; Deserio-Cuesta, Julio Alberto; Soria-Navarro, Raquel; Vilar-Sastre, Inca; Martinez-Cadenas, Conrado

2018-03-01

Prediction of human pigmentation traits, one of the most differentiable externally visible characteristics among individuals, from biological samples represents a useful tool in the field of forensic DNA phenotyping. In spite of freckling being a relatively common pigmentation characteristic in Europeans, little is known about the genetic basis of this largely genetically determined phenotype in southern European populations. In this work, we explored the predictive capacity of eight freckle and sunlight sensitivity-related genes in 458 individuals (266 non-freckled controls and 192 freckled cases) from Spain. Four loci were associated with freckling (MC1R, IRF4, ASIP and BNC2), and female sex was also found to be a predictive factor for having a freckling phenotype in our population. After identifying the most informative genetic variants responsible for human ephelides occurrence in our sample set, we developed a DNA-based freckle prediction model using a multivariate regression approach. Once developed, the capabilities of the prediction model were tested by a repeated 10-fold cross-validation approach. The proportion of correctly predicted individuals using the DNA-based freckle prediction model was 74.13%. The implementation of sex into the DNA-based freckle prediction model slightly improved the overall prediction accuracy by 2.19% (76.32%). Further evaluation of the newly-generated prediction model was performed by assessing the model's performance in a new cohort of 212 Spanish individuals, reaching a classification success rate of 74.61%. Validation of this prediction model may be carried out in larger populations, including samples from different European populations. Further research to validate and improve this newly-generated freckle prediction model will be needed before its forensic application. Together with DNA tests already validated for eye and hair colour prediction, this freckle prediction model may lead to a substantially more detailed physical description of unknown individuals from DNA found at the crime scene. Copyright © 2017 Elsevier B.V. All rights reserved.

Time for Genome Editing: Next-Generation Attenuated Malaria Parasites.

PubMed

Singer, Mirko; Frischknecht, Friedrich

2017-03-01

Immunization with malaria parasites that developmentally arrest in or immediately after the liver stage is the only way currently known to confer sterilizing immunity in both humans and rodent models. There are various ways to attenuate parasite development resulting in different timings of arrest, which has a significant impact on vaccination efficiency. To understand what most impacts vaccination efficiency, newly developed gain-of-function methods can now be used to generate a wide array of differently attenuated parasites. The combination of multiple attenuation approaches offers the potential to engineer efficiently attenuated Plasmodium parasites and learn about their fascinating biology at the same time. Here we discuss recent studies and the potential of targeted parasite manipulation using genome editing to develop live attenuated malaria vaccines. Copyright © 2016 Elsevier Ltd. All rights reserved.

Risk-Aware Planetary Rover Operation: Autonomous Terrain Classification and Path Planning

NASA Technical Reports Server (NTRS)

Ono, Masahiro; Fuchs, Thoams J.; Steffy, Amanda; Maimone, Mark; Yen, Jeng

2015-01-01

Identifying and avoiding terrain hazards (e.g., soft soil and pointy embedded rocks) are crucial for the safety of planetary rovers. This paper presents a newly developed groundbased Mars rover operation tool that mitigates risks from terrain by automatically identifying hazards on the terrain, evaluating their risks, and suggesting operators safe paths options that avoids potential risks while achieving specified goals. The tool will bring benefits to rover operations by reducing operation cost, by reducing cognitive load of rover operators, by preventing human errors, and most importantly, by significantly reducing the risk of the loss of rovers.

Alternative polyadenylation: New insights from global analyses

PubMed Central

Shi, Yongsheng

2012-01-01

Recent studies have revealed widespread mRNA alternative polyadenylation (APA) in eukaryotes and its dynamic spatial and temporal regulation. APA not only generates proteomic and functional diversity, but also plays important roles in regulating gene expression. Global deregulation of APA has been demonstrated in a variety of human diseases. Recent exciting advances in the field have been made possible in a large part by high throughput analyses using newly developed experimental tools. Here I review the recent progress in global studies of APA and the insights that have emerged from these and other studies that use more conventional methods. PMID:23097429

Nanotherapeutics--product development along the "nanomaterial" discussion.

PubMed

Wacker, Matthias G

2014-03-01

Nanomaterials have become part of formulation development in the pharmaceutical industry and offer exciting opportunities in the area of targeted drug delivery. But they may also exert unexpected toxicities and potentially pose a threat to human health and the environment. Since the Scientific Committee on Emerging and Newly Identified Health Risks recommended a definition of "nanomaterials" for implementation into the existing and upcoming regulatory framework in the European Union, a discussion about safety requirements of new nanoscale products has emerged. At the same time, the Food and Drug Administration of the United States still observes recent developments in this area. Although the impact on the pharmaceutical product chain is still uncertain, guidelines on risk assessment in food products and cosmetics are available and offer a preview of future developments in the regimens of pharmaceuticals. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

Development of a rhesus monkey lung geometry model and application to particle deposition in comparison to humans

DOE Office of Scientific and Technical Information (OSTI.GOV)

Asgharian, Bahman; Price, Owen; McClellan, Gene

2012-11-01

The exposure-dose-response characterization of an inhalation hazard established in an animal species needs to be translated to an equivalent characterization in humans relative to comparable doses or exposure scenarios. Here, the first geometry model of the conducting airways for rhesus monkeys is developed based upon CT images of the conducting airways of a 6-month-old male, rhesus monkey. An algorithm was developed for adding the alveolar region airways using published rhesus morphometric data. The resultant lung geometry model can be used in mechanistic particle or gaseous dosimetry models. Such dosimetry models require estimates of the upper respiratory tract volume of themore » animal and the functional residual capacity, as well as of the tidal volume and breathing frequency of the animal. The relationship of these variables to rhesus monkeys of differing body weights was established by synthesizing and modeling published data as well as modeling pulmonary function measurements on 121 rhesus control animals. Deposition patterns of particles up to 10 µm in size were examined for endotracheal and and up to 5 µm for spontaneous breathing in infant and young adult monkeys and compared to those for humans. Deposition fraction of respirable size particles was found to be higher in the conducting airways of infant and young adult rhesus monkeys compared to humans. Due to the filtering effect of the conducting airways, pulmonary deposition in rhesus monkeys was lower than that in humans. Finally, future research areas are identified that would either allow replacing assumptions or improving the newly developed lung model.« less

Development of a rhesus monkey lung geometry model and application to particle deposition in comparison to humans

PubMed Central

Asgharian, Bahman; Price, Owen; McClellan, Gene; Corley, Rick; Einstein, Daniel R.; Jacob, Richard E.; Harkema, Jack; Carey, Stephan A.; Schelegle, Edward; Hyde, Dallas; Kimbell, Julia S.; Miller, Frederick J.

2016-01-01

The exposure-dose-response characterization of an inhalation hazard established in an animal species needs to be translated to an equivalent characterization in humans relative to comparable doses or exposure scenarios. Here, the first geometry model of the conducting airways for rhesus monkeys is developed based upon CT images of the conducting airways of a 6-month-old male, rhesus monkey. An algorithm was developed for adding the alveolar region airways using published rhesus morphometric data. The resultant lung geometry model can be used in mechanistic particle or gaseous dosimetry models. Such dosimetry models require estimates of the upper respiratory tract volume of the animal and the functional residual capacity, as well as of the tidal volume and breathing frequency of the animal. The relationship of these variables to rhesus monkeys of differing body weights was established by synthesizing and modeling published data as well as modeling pulmonary function measurements on 121 rhesus control animals. Deposition patterns of particles up to 10 μm in size were examined for endotracheal and and up to 5 μm for spontaneous breathing in infant and young adult monkeys and compared to those for humans. Deposition fraction of respirable size particles was found to be higher in the conducting airways of infant and young adult rhesus monkeys compared to humans. Due to the filtering effect of the conducting airways, pulmonary deposition in rhesus monkeys was lower than that in humans. Future research areas are identified that would either allow replacing assumptions or improving the newly developed lung model. PMID:23121298

Development of a high-throughput assay for human proprotein convertase 5/6 for detecting uterine receptivity.

PubMed

Heng, Sophea; Dynon, Kemperly; Li, Ying; Edgell, Tracey; Walton, Kelly; Rombauts, Luk J; Vollenhoven, Beverley; Nie, Guiying

2015-04-15

Embryo implantation requires a healthy embryo and a receptive uterus. In women, the inner lining of the uterus, the endometrium, remains in a hostile state and becomes receptive for embryo implantation for only a short period during each menstrual cycle. Determining endometrial receptivity is vital in in vitro fertilization (IVF) treatment because the timing of embryo transfer needs to be synchronized with endometrial receptivity. We have previously demonstrated that proprotein convertase 5/6A (PC6) is highly expressed in the receptive endometrium and that PC6 is critical for receptivity establishment in women. Furthermore, endometrial PC6 is secreted into the uterine fluid, and levels correlate with receptivity status. Detection of PC6 in uterine fluids, therefore, would provide a nonsurgical assessment of endometrial receptivity. However, to date no assays are available for human PC6. In this study, we produced three PC6 monoclonal antibodies (mAbs) and developed a sandwich enzyme-linked immunosorbent assay (ELISA) for PC6 detection in human uterine fluids. The PC6 mAbs were confirmed to be highly specific to PC6, and the ELISA detected PC6 in human uterine fluids with a significantly higher level during the receptive phase. This newly established PC6 ELISA provides an important tool in the development of noninvasive strategies to detect endometrial receptivity in women. Copyright © 2015. Published by Elsevier Inc.

NanoCluster Beacons as reporter probes in rolling circle enhanced enzyme activity detection

NASA Astrophysics Data System (ADS)

Juul, Sissel; Obliosca, Judy M.; Liu, Cong; Liu, Yen-Liang; Chen, Yu-An; Imphean, Darren M.; Knudsen, Birgitta R.; Ho, Yi-Ping; Leong, Kam W.; Yeh, Hsin-Chih

2015-04-01

As a newly developed assay for the detection of endogenous enzyme activity at the single-catalytic-event level, Rolling Circle Enhanced Enzyme Activity Detection (REEAD) has been used to measure enzyme activity in both single human cells and malaria-causing parasites, Plasmodium sp. Current REEAD assays rely on organic dye-tagged linear DNA probes to report the rolling circle amplification products (RCPs), the cost of which may hinder the widespread use of REEAD. Here we show that a new class of activatable probes, NanoCluster Beacons (NCBs), can simplify the REEAD assays. Easily prepared without any need for purification and capable of large fluorescence enhancement upon hybridization, NCBs are cost-effective and sensitive. Compared to conventional fluorescent probes, NCBs are also more photostable. As demonstrated in reporting the human topoisomerases I (hTopI) cleavage-ligation reaction, the proposed NCBs suggest a read-out format attractive for future REEAD-based diagnostics.As a newly developed assay for the detection of endogenous enzyme activity at the single-catalytic-event level, Rolling Circle Enhanced Enzyme Activity Detection (REEAD) has been used to measure enzyme activity in both single human cells and malaria-causing parasites, Plasmodium sp. Current REEAD assays rely on organic dye-tagged linear DNA probes to report the rolling circle amplification products (RCPs), the cost of which may hinder the widespread use of REEAD. Here we show that a new class of activatable probes, NanoCluster Beacons (NCBs), can simplify the REEAD assays. Easily prepared without any need for purification and capable of large fluorescence enhancement upon hybridization, NCBs are cost-effective and sensitive. Compared to conventional fluorescent probes, NCBs are also more photostable. As demonstrated in reporting the human topoisomerases I (hTopI) cleavage-ligation reaction, the proposed NCBs suggest a read-out format attractive for future REEAD-based diagnostics. Electronic supplementary information (ESI) available: The detailed steps of NCB preparation, REEAD assay and STEM imaging. The sequences of the sNCB and the REEAD substrate. See DOI: 10.1039/c5nr01705j

Macrobenthic diversity in protected, disturbed, and newly formed intertidal wetlands of a subtropical estuary in China.

PubMed

Lv, Weiwei; Ma, Chang-An; Huang, Youhui; Yang, Yang; Yu, Ji; Zhang, Mingqing; Zhao, Yunlong

2014-12-15

In this study, intertidal macrobenthic diversity in protected, disturbed, and newly formed wetlands of Yangtze estuary was assessed using PRIMER 5.2 based on species diversity and species relatedness. We observed high diversity in nature reserves and low diversity in adjacent disturbed and newly formed wetlands. These diversity data were then integrated with historical data to detect the variation in macrobenthic diversity over the past two decades. The integrated data indicated that the intertidal macrobenthic diversity sharply decreased in heavy reclamation tidal flats whereas markedly increased in non-disturbed nature reserve and newly formed wetland. Benthic health was observed with the departure degree of average taxonomic distinctness (Δ(+)) and variation in taxonomic distinctness (Λ(+)) from the simulated 95% confidence funnel. All the habitats were subjected to different levels of human interference, except Jiuduansha and Beigangbeisha. The degradation of intertidal wetland in Yangtze estuary was mainly attributed to land reclamation, overgrazing, and overfishing. Copyright © 2014 Elsevier Ltd. All rights reserved.

Tick-Borne Pathogen – Reversed and Conventional Discovery of Disease

PubMed Central

Tijsse-Klasen, Ellen; Koopmans, Marion P. G.; Sprong, Hein

2014-01-01

Molecular methods have increased the number of known microorganisms associated with ticks significantly. Some of these newly identified microorganisms are readily linked to human disease while others are yet unknown to cause human disease. The face of tick-borne disease discovery has changed with more diseases now being discovered in a “reversed way,” detecting disease cases only years after the tick-borne microorganism was first discovered. Compared to the conventional discovery of infectious diseases, reverse order discovery presents researchers with new challenges. Estimating public health risks of such agents is especially challenging, as case definitions and diagnostic procedures may initially be missing. We discuss the advantages and shortcomings of molecular methods, serology, and epidemiological studies that might be used to study some fundamental questions regarding newly identified tick-borne diseases. With increased tick-exposure and improved detection methods, more tick-borne microorganisms will be added to the list of pathogens causing disease in humans in the future. PMID:25072045

DEVELOPMENT OF CRASSPHAGE-BASED QPCR ASSAYS ...

EPA Pesticide Factsheets

A newly discovered bacteriophage, “crAssphage”, is predicted to be both highlyabundant and predominantly human-associated, both ideal characteristics for a human-specific fecal indicator. A total of 384 end-point PCR primers were designed along the length of the crAssphage genome, eliminating regions suspected to be hypervariable or react with other animal sources. The primer pairs were rigorously tested in three rounds of screening for specificity, geographic variability, limit of detection, and environmental water performance. The two best performing assays, crAss056 and crAss064, were adapted to a qPCR platform and exhibited a specificity of 98.0% and 98.9%, respectively. The markers’ abundance was compared with two bacterial based assays and were found at concentrations at or above the bacterial based assays in wastewater influent and impacted environmental waters. This poster will present the methodology of the novel marker development and the potential uses for this technology in maintaining sustainable waterways in the future. To inform the public.

Identification of a candidate therapeutic autophagy–inducing peptide

PubMed Central

Shoji-Kawata, Sanae; Sumpter, Rhea; Leveno, Matthew; Campbell, Grant R.; Zou, Zhongju; Kinch, Lisa; Wilkins, Angela D.; Sun, Qihua; Pallauf, Kathrin; MacDuff, Donna; Huerta, Carlos; Virgin, Herbert W.; Helms, J. Bernd; Eerland, Ruud; Tooze, Sharon A.; Xavier, Ramnik; Lenschow, Deborah J.; Yamamoto, Ai; King, David; Lichtarge, Olivier; Grishin, Nick V.; Spector, Stephen A.; Kaloyanova, Dora V.; Levine, Beth

2013-01-01

The lysosomal degradation pathway of autophagy has a crucial role in defence against infection, neurodegenerative disorders, cancer and ageing. Accordingly, agents that induce autophagy may have broad therapeutic applications. One approach to developing such agents is to exploit autophagy manipulation strategies used by microbial virulence factors. Here we show that a peptide, Tat–beclin 1—derived from a region of the autophagy protein, beclin 1, which binds human immunodeficiency virus (HIV)-1 Nef—is a potent inducer of autophagy, and interacts with a newly identified negative regulator of autophagy, GAPR-1 (also called GLIPR2). Tat–beclin 1 decreases the accumulation of polyglutamine expansion protein aggregates and the replication of several pathogens (including HIV-1) in vitro, and reduces mortality in mice infected with chikungunya or West Nile virus. Thus, through the characterization of a domain of beclin 1 that interacts with HIV-1 Nef, we have developed an autophagy-inducing peptide that has potential efficacy in the treatment of human diseases. PMID:23364696

Fear, pandemonium, equanimity and delight: human responses to extra-terrestrial life.

PubMed

Harrison, Albert A

2011-02-13

How will people respond to the discovery of extra-terrestrial life? Potentially useful resources for addressing this question include historical prototypes, disaster studies and survey research. Reactions will depend on the interplay of the characteristics of the newly found life, the unfolding of the discovery, the context and content of the message and human information processing as shaped by biology, culture and psychology. Pre-existing images of extra-terrestrials as god-like, demonic, or artificial will influence first impressions that may prove highly resistant to change. Most probably people will develop comprehensive images based on minimal information and assess extra-terrestrials in the same ways that they assess one another. Although it is easy to develop frightening scenarios, finding microbial life in our Solar System or intercepting a microwave transmission from many light years away are less likely to be met with adverse reactions such as fear and pandemonium than with positive reactions such as equanimity and delight.

Human interleukin for DA cells or leukemia inhibitory factor is released by Vero cells in human embryo coculture.

PubMed

Papaxanthos-Roche, A; Taupin, J L; Mayer, G; Daniel, J Y; Moreau, J F

1994-09-01

In the light of the newly discovered implications of human interleukin for DA cells and leukemia inhibitory factor in embryology, we searched for the presence of this soluble cytokine in the supernatant of Vero cell coculture systems. Using a bioassay as well as a specific ELISA, we demonstrated that Vero cells are able to release large quantities of human interleukin for DA cells and leukemia inhibitory factor in the embryo-growing medium of such cocultures.

Establishment of a new conditionally immortalized cell line from human brain microvascular endothelial cells: a promising tool for human blood-brain barrier studies.

PubMed

Kamiichi, Atsuko; Furihata, Tomomi; Kishida, Satoshi; Ohta, Yuki; Saito, Kosuke; Kawamatsu, Shinya; Chiba, Kan

2012-12-07

The blood-brain barrier (BBB) is formed by brain microvascular endothelial cells (BMEC) working together with astrocytes and pericytes, in which tight junctions and various transporters strictly regulate the penetration of diverse compounds into the brain. Clarification of the molecular machinery that provides such regulation using in vitro BBB models has provided important insights into the roles of the BBB in central nervous system (CNS) disorders and CNS drug development. In this study, we succeeded in establishing a new cell line, hereinafter referred to as human BMEC/conditionally immortalized, clone β (HBMEC/ciβ), as part of our ongoing efforts to develop an in vitro human BBB model. Our results showed that HBMEC/ciβ proliferated well. Furthermore, we found that HBMEC/ciβ exhibited the barrier property of restricting small molecule intercellular penetration and possessed effective efflux transporter functions, both of which are essential to a functioning BBB. Because higher temperatures are known to terminate immortalization signals, we specifically examined the effects of higher temperatures on the HBMEC/ciβ differentiation status. The results showed that higher temperatures stimulated HBMEC/ciβ differentiation, marked by morphological alteration and increases in several mRNA levels. To summarize, our data indicates that the newly established HBMEC/ciβ offers a promising tool for use in the development of a practical in vitro human BBB model that could make significant contributions toward understanding the molecular biology of CNS disorders, as well as to CNS drug development. It is also believed that the development of a specific culture method for HBMEC/ciβ will add significant value to the HBMEC/ciβ-based BBB model. Copyright © 2012 Elsevier B.V. All rights reserved.

The importance of the Non Obese Diabetic (NOD) mouse model in autoimmune diabetes

PubMed Central

Pearson, James A; Wong, F. Susan; Wen, Li

2016-01-01

Type 1 Diabetes (T1D) is an autoimmune disease characterized by the pancreatic infiltration of immune cells resulting in T cell-mediated destruction of the insulin-producing beta cells. The successes of the Non Obese Diabetic (NOD) mouse model have come in multiple forms including identifying key genetic and environmental risk factors e.g. Idd loci and effects of microorganisms including the gut microbiota, respectively, and how they may contribute to disease susceptibility and pathogenesis. Furthermore, the NOD model also provides insights into the roles of the innate immune cells as well as the B cells in contributing to the T cell-mediated disease. Unlike many autoimmune disease models, the NOD mouse develops spontaneous disease and has many similarities to human T1D. Through exploiting these similarities many targets have been identified for immune-intervention strategies. Although many of these immunotherapies did not have a significant impact on human T1D, they have been shown to be effective in the NOD mouse in early stage disease, which is not equivalent to trials in newly-diagnosed patients with diabetes. However, the continued development of humanized NOD mice would enable further clinical developments, bringing T1D research to a new translational level. Therefore, it is the aim of this review to discuss the importance of the NOD model in identifying the roles of the innate immune system and the interaction with the gut microbiota in modifying diabetes susceptibility. In addition, the role of the B cells will also be discussed with new insights gained through B cell depletion experiments and the impact on translational developments. Finally, this review will also discuss the future of the NOD mice and the development of humanized NOD mice, providing novel insights into human T1D. PMID:26403950

New clustered regularly interspaced short palindromic repeat locus spacer pair typing method based on the newly incorporated spacer for Salmonella enterica.

PubMed

Li, Hao; Li, Peng; Xie, Jing; Yi, Shengjie; Yang, Chaojie; Wang, Jian; Sun, Jichao; Liu, Nan; Wang, Xu; Wu, Zhihao; Wang, Ligui; Hao, Rongzhang; Wang, Yong; Jia, Leili; Li, Kaiqin; Qiu, Shaofu; Song, Hongbin

2014-08-01

A clustered regularly interspaced short palindromic repeat (CRISPR) typing method has recently been developed and used for typing and subtyping of Salmonella spp., but it is complicated and labor intensive because it has to analyze all spacers in two CRISPR loci. Here, we developed a more convenient and efficient method, namely, CRISPR locus spacer pair typing (CLSPT), which only needs to analyze the two newly incorporated spacers adjoining the leader array in the two CRISPR loci. We analyzed a CRISPR array of 82 strains belonging to 21 Salmonella serovars isolated from humans in different areas of China by using this new method. We also retrieved the newly incorporated spacers in each CRISPR locus of 537 Salmonella isolates which have definite serotypes in the Pasteur Institute's CRISPR Database to evaluate this method. Our findings showed that this new CLSPT method presents a high level of consistency (kappa = 0.9872, Matthew's correlation coefficient = 0.9712) with the results of traditional serotyping, and thus, it can also be used to predict serotypes of Salmonella spp. Moreover, this new method has a considerable discriminatory power (discriminatory index [DI] = 0.8145), comparable to those of multilocus sequence typing (DI = 0.8088) and conventional CRISPR typing (DI = 0.8684). Because CLSPT only costs about $5 to $10 per isolate, it is a much cheaper and more attractive method for subtyping of Salmonella isolates. In conclusion, this new method will provide considerable advantages over other molecular subtyping methods, and it may become a valuable epidemiologic tool for the surveillance of Salmonella infections. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Constructing Practical Knowledge of Teaching: Eleven Newly Qualified Language Teachers' Discursive Agency

ERIC Educational Resources Information Center

Ruohotie-Lyhty, Maria

2011-01-01

This paper explores the professional development of 11 newly qualified foreign language teachers. It draws on a qualitative longitudinal study conducted at the University of Jyvaskyla, Finland between 2002 and 2009. The paper concentrates on the personal side of teacher development by analysing participants' discourses concerning language…

Emergence of Human Arboviral Diseases in the Americas, 2000-2016.

PubMed

Vasconcelos, Pedro F C; Calisher, Charles H

2016-05-01

In addition to individual or clusters of cases of human infections with arboviruses, the past 15 years has seen the emergence of newly recognized arboviruses and the re-emergence of others. Mentioned in this brief summary are Bourbon, Cache Valley, chikungunya, Heartland, Itaqui, Mayaro, Oropouche, Powassan, and Zika viruses, the latter being a remarkable occurrence.

Parenteral Transmission of the Novel Human Parvovirus PARV4

PubMed Central

Manning, Ashleigh; Kenneil, Rachel; Carnie, Frances W.; Bell, Jeanne E.

2007-01-01

Transmission routes of PARV4, a newly discovered human parvovirus, were investigated by determining frequencies of persistent infections using autopsy samples from different risk groups. Predominantly parenteral routes of transmission were demonstrated by infection restricted to injection drug users and persons with hemophilia and absence of infection in homosexual men with AIDS and low-risk controls. PMID:18252117

Determination of imidocarb residues in bovine and ovine liver and milk by immunobiosensor.

PubMed

Traynor, I M; Thompson, C S; Armstrong, L; Fodey, T; Danaher, M; Jordan, K; Kennedy, D G; Crooks, S R H

2013-01-01

Imidocarb (IMD) is a veterinary drug that has been used for more than 30 years to treat and prevent parasitic diseases. Pharmacokinetic studies have shown that substantial levels of IMD residues are retained in the edible tissues and milk of cattle and sheep for up to 6 months after administration. This has led to concern regarding the potential adverse effects posed through human consumption of edible tissue or milk from treated animals if the recommended withdrawal periods for the drug are not properly implemented. While MRLs have been established by the European Union, it is important that analytical methods are available to monitor food samples for potentially violative levels of IMD residues. A qualitative biosensor-based immunoassay was developed to allow the detection of IMD at less than the European Union MRLs of 50 μg kg(-1) for milk and 2 mg kg(-1) for bovine and ovine liver. Validation of the developed methods provided a detection capability of <25 μg kg(-1) in milk and <0.75 mg kg(-1) in liver. A comparison study was undertaken, with IMD incurred milk and ovine liver samples analysed by the newly developed procedures and results compared with those obtained by LC-MS/MS. The newly developed screening method was applied to both incurred milk and liver samples. This faster, cheaper and reliable screening method has potential use in sample analysis to ensure compliance with legislative requirements.

Understanding high endothelial venules: Lessons for cancer immunology

PubMed Central

Ager, Ann; May, Michael J

2015-01-01

High endothelial venules (HEVs) are blood vessels especially adapted for lymphocyte trafficking which are normally found in secondary lymphoid organs such as lymph nodes (LN) and Peyer's patches. It has long been known that HEVs develop in non-lymphoid organs during chronic inflammation driven by autoimmunity, infection or allografts. More recently, HEVs have been observed in solid, vascularized tumors and their presence correlated with reduced tumor size and improved patient outcome. It is proposed that newly formed HEV promote antitumor immunity by recruiting naive lymphocytes into the tumor, thus allowing the local generation of cancerous tissue-destroying lymphocytes. Understanding how HEVs develop and function are therefore important to unravel their role in human cancers. In LN, HEVs develop during embryonic and early post-natal life and are actively maintained by the LN microenvironment. Systemic blockade of lymphotoxin-β receptor leads to HEV de-differentiation, but the LN components that induce HEV differentiation have remained elusive. Recent elegant studies using gene-targeted mice have demonstrated clearly that triggering the lymphotoxin-β receptor in endothelial cells (EC) induces the differentiation of HEV and that CD11c+ dendritic cells play a crucial role in this process. It will be important to determine whether lymphotoxin-β receptor-dependent signaling in EC drives the development of HEV during tumorigenesis and which cells have HEV-inducer properties. This may reveal therapeutic approaches to promote HEV neogenesis and determine the impact of newly formed HEV on tumor immunity. PMID:26155419

Determination of selected neurotoxic insecticides in small amounts of animal tissue utilizing a newly constructed mini-extractor.

PubMed

Seifertová, Marta; Čechová, Eliška; Llansola, Marta; Felipo, Vicente; Vykoukalová, Martina; Kočan, Anton

2017-10-01

We developed a simple analytical method for the simultaneous determination of representatives of various groups of neurotoxic insecticides (carbaryl, chlorpyrifos, cypermethrin, and α-endosulfan and β-endosulfan and their metabolite endosulfan sulfate) in limited amounts of animal tissues containing different amounts of lipids. Selected tissues (rodent fat, liver, and brain) were extracted in a special in-house-designed mini-extractor constructed on the basis of the Soxhlet and Twisselmann extractors. A dried tissue sample placed in a small cartridge was extracted, while the nascent extract was simultaneously filtered through a layer of sodium sulfate. The extraction was followed by combined clean-up, including gel permeation chromatography (in case of high lipid content), ultrasonication, and solid-phase extraction chromatography using C 18 on silica and aluminum oxide. Gas chromatography coupled with high-resolution mass spectrometry was used for analyte separation, detection, and quantification. Average recoveries for individual insecticides ranged from 82 to 111%. Expanded measurement uncertainties were generally lower than 35%. The developed method was successfully applied to rat tissue samples obtained from an animal model dealing with insecticide exposure during brain development. This method may also be applied to the analytical treatment of small amounts of various types of animal and human tissue samples. A significant advantage achieved using this method is high sample throughput due to the simultaneous treatment of many samples. Graphical abstract Optimized workflow for the determination of selected insecticides in small amounts of animal tissue including newly developed mini-extractor.

Cockpit System Situational Awareness Modeling Tool

NASA Technical Reports Server (NTRS)

Keller, John; Lebiere, Christian; Shay, Rick; Latorella, Kara

2004-01-01

This project explored the possibility of predicting pilot situational awareness (SA) using human performance modeling techniques for the purpose of evaluating developing cockpit systems. The Improved Performance Research Integration Tool (IMPRINT) was combined with the Adaptive Control of Thought-Rational (ACT-R) cognitive modeling architecture to produce a tool that can model both the discrete tasks of pilots and the cognitive processes associated with SA. The techniques for using this tool to predict SA were demonstrated using the newly developed Aviation Weather Information (AWIN) system. By providing an SA prediction tool to cockpit system designers, cockpit concepts can be assessed early in the design process while providing a cost-effective complement to the traditional pilot-in-the-loop experiments and data collection techniques.

Thermoelectric property measurements with computer controlled systems

NASA Technical Reports Server (NTRS)

Chmielewski, A. B.; Wood, C.

1984-01-01

A joint JPL-NASA program to develop an automated system to measure the thermoelectric properties of newly developed materials is described. Consideration is given to the difficulties created by signal drift in measurements of Hall voltage and the Large Delta T Seebeck coefficient. The benefits of a computerized system were examined with respect to error reduction and time savings for human operators. It is shown that the time required to measure Hall voltage can be reduced by a factor of 10 when a computer is used to fit a curve to the ratio of the measured signal and its standard deviation. The accuracy of measurements of the Large Delta T Seebeck coefficient and thermal diffusivity was also enhanced by the use of computers.

A Newly Defined and Xeno-Free Culture Medium Supports Every-Other-Day Medium Replacement in the Generation and Long-Term Cultivation of Human Pluripotent Stem Cells.

PubMed

Ahmadian Baghbaderani, Behnam; Tian, Xinghui; Scotty Cadet, Jean; Shah, Kevan; Walde, Amy; Tran, Huan; Kovarcik, Don Paul; Clarke, Diana; Fellner, Thomas

2016-01-01

Human pluripotent stem cells (hPSCs) present an unprecedented opportunity to advance human health by offering an alternative and renewable cell resource for cellular therapeutics and regenerative medicine. The present demand for high quality hPSCs for use in both research and clinical studies underscores the need to develop technologies that will simplify the cultivation process and control variability. Here we describe the development of a robust, defined and xeno-free hPSC medium that supports reliable propagation of hPSCs and generation of human induced pluripotent stem cells (hiPSCs) from multiple somatic cell types; long-term serial subculturing of hPSCs with every-other-day (EOD) medium replacement; and banking fully characterized hPSCs. The hPSCs cultured in this medium for over 40 passages are genetically stable, retain high expression levels of the pluripotency markers TRA-1-60, TRA-1-81, Oct-3/4 and SSEA-4, and readily differentiate into ectoderm, mesoderm and endoderm. Importantly, the medium plays an integral role in establishing a cGMP-compliant process for the manufacturing of hiPSCs that can be used for generation of clinically relevant cell types for cell replacement therapy applications.

Antibody Responses in Humans Infected with Newly Emerging Strains of West Nile Virus in Europe

PubMed Central

Chabierski, Stefan; Makert, Gustavo R.; Kerzhner, Alexandra; Barzon, Luisa; Fiebig, Petra; Liebert, Uwe G.; Papa, Anna; Richner, Justin M.; Niedrig, Matthias; Diamond, Michael S.; Palù, Giorgio; Ulbert, Sebastian

2013-01-01

Infection with West Nile Virus (WNV) affects an increasing number of countries worldwide. Although most human infections result in no or mild flu-like symptoms, the elderly and those with a weakened immune system are at higher risk for developing severe neurological disease. Since its introduction into North America in 1999, WNV has spread across the continental United States and caused annual outbreaks with a total of 36,000 documented clinical cases and ∼1,500 deaths. In recent years, outbreaks of neuroinvasive disease also have been reported in Europe. The WNV strains isolated during these outbreaks differ from those in North America, as sequencing has revealed that distinct phylogenetic lineages of WNV concurrently circulate in Europe, which has potential implications for the development of vaccines, therapeutics, and diagnostic tests. Here, we studied the human antibody response to European WNV strains responsible for outbreaks in Italy and Greece in 2010, caused by lineage 1 and 2 strains, respectively. The WNV structural proteins were expressed as a series of overlapping fragments fused to a carrier-protein, and binding of IgG in sera from infected persons was analyzed. The results demonstrate that, although the humoral immune response to WNV in humans is heterogeneous, several dominant peptides are recognized. PMID:23776680

Antibody responses in humans infected with newly emerging strains of West Nile Virus in Europe.

PubMed

Chabierski, Stefan; Makert, Gustavo R; Kerzhner, Alexandra; Barzon, Luisa; Fiebig, Petra; Liebert, Uwe G; Papa, Anna; Richner, Justin M; Niedrig, Matthias; Diamond, Michael S; Palù, Giorgio; Ulbert, Sebastian

2013-01-01

Infection with West Nile Virus (WNV) affects an increasing number of countries worldwide. Although most human infections result in no or mild flu-like symptoms, the elderly and those with a weakened immune system are at higher risk for developing severe neurological disease. Since its introduction into North America in 1999, WNV has spread across the continental United States and caused annual outbreaks with a total of 36,000 documented clinical cases and ∼1,500 deaths. In recent years, outbreaks of neuroinvasive disease also have been reported in Europe. The WNV strains isolated during these outbreaks differ from those in North America, as sequencing has revealed that distinct phylogenetic lineages of WNV concurrently circulate in Europe, which has potential implications for the development of vaccines, therapeutics, and diagnostic tests. Here, we studied the human antibody response to European WNV strains responsible for outbreaks in Italy and Greece in 2010, caused by lineage 1 and 2 strains, respectively. The WNV structural proteins were expressed as a series of overlapping fragments fused to a carrier-protein, and binding of IgG in sera from infected persons was analyzed. The results demonstrate that, although the humoral immune response to WNV in humans is heterogeneous, several dominant peptides are recognized.

Insect-specific viruses and their potential impact on arbovirus transmission.

PubMed

Vasilakis, Nikos; Tesh, Robert B

2015-12-01

Arthropod-borne viruses (arboviruses) are the causative agents of significant morbidity and mortality among humans and animals globally. In the past few years, the widespread adoption of next generation sequencing and metagenomics has led to a new era of virus discovery, where many novel viruses have been documented, exhibiting a restricted host-range in mosquitoes. They represent a wide-range of insect-specific viruses within the families of Bunyaviridae, Flaviviridae, Mesoniviridae, Reoviridae, Rhabdoviridae, Togaviridae, and the newly recognized taxon of Negeviruses. Collectively, their discovery has opened new vistas about the extent of viral diversity and evolution, their influence on vector competence and ability of their insect hosts to transmit human pathogens (e.g. arboviruses), and their potential development as biological control agents or novel vaccine platforms. Copyright © 2015 Elsevier B.V. All rights reserved.

SMART Digest™ compared with pellet digestion for analysis of human immunoglobulin G1 in rat serum by liquid chromatography tandem mass spectrometry.

PubMed

Lanshoeft, Christian; Heudi, Olivier; Cianférani, Sarah

2016-05-15

The newly developed SMART Digest™ kit was applied for the sample preparation of human immunoglobulin G1 (hIgG1) in rat serum prior to qualitative and quantitative analyses by liquid chromatography tandem mass spectrometry (LC-MS/MS). The sequence coverages obtained for the light and heavy chains of hIgG1A were 50 and 76%, respectively. The calibration curve was linear from 1.00 to 1000 μg/ml for three of four generic peptides. Overall, the SMART Digest™ kit resulted in similar quantitative data (linearity, sensitivity, accuracy, and precision) compared with the pellet digestion protocol. However, the SMART Digest™ required only 2 h of sample preparation with fewer reagents. Copyright © 2016 Elsevier Inc. All rights reserved.

Identifying governance strategies that effectively support ecosystem services, resource sustainability, and biodiversity

PubMed Central

Kenward, R. E.; Whittingham, M. J.; Arampatzis, S.; Manos, B. D.; Hahn, T.; Terry, A.; Simoncini, R.; Alcorn, J.; Bastian, O.; Donlan, M.; Elowe, K.; Franzén, F.; Karacsonyi, Z.; Larsson, M.; Manou, D.; Navodaru, I.; Papadopoulou, O.; Papathanasiou, J.; von Raggamby, A.; Sharp, R. J. A.; Söderqvist, T.; Soutukorva, Å.; Vavrova, L.; Aebischer, N. J.; Leader-Williams, N.; Rutz, C.

2011-01-01

Conservation scientists, national governments, and international conservation groups seek to devise, and implement, governance strategies that mitigate human impact on the environment. However, few studies to date have systematically investigated the performance of different systems of governance in achieving successful conservation outcomes. Here, we use a newly-developed analytic framework to conduct analyses of a suite of case studies, linking different governance strategies to standardized scores for delivering ecosystem services, achieving sustainable use of natural resources, and conserving biodiversity, at both local and international levels. Our results: (i) confirm the benefits of adaptive management; and (ii) reveal strong associations for the role of leadership. Our work provides a critical step toward implementing empirically justified governance strategies that are capable of improving the management of human-altered environments, with benefits for both biodiversity and people. PMID:21402916

Translating transitions – how to decipher peripheral human B cell development

PubMed Central

Bemark, Mats

2015-01-01

Abstract During the last two decades our understanding of human B cell differentiation has developed considerably. Our understanding of the human B cell compartment has advanced from a point where essentially all assays were based on the presence or not of class-switched antibodies to a level where a substantial diversity is appreciated among the cells involved. Several consecutive transitional stages that newly formed IgM expressing B cells go through after they leave the bone marrow, but before they are fully mature, have been described, and a significant complexity is also acknowledged within the IgM expressing and class-switched memory B cell compartments. It is possible to isolate plasma blasts in blood to follow the formation of plasma cells during immune responses, and the importance and uniqueness of the mucosal IgA system is now much more appreciated. Current data suggest the presence of at least one lineage of human innate-like B cells akin to B1 and/or marginal zone B cells in mice. In addition, regulatory B cells with the ability to produce IL-10 have been identified. Clinically, B cell depletion therapy is used for a broad range of conditions. The ability to define different human B cell subtypes using flow cytometry has therefore started to come into clinical use, but as our understanding of human B cell development further progresses, B cell subtype analysis will be of increasing importance in diagnosis, to measure the effect of immune therapy and to understand the underlying causes for diseases. In this review the diversity of human B cells will be discussed, with special focus on current data regarding their phenotypes and functions. PMID:26243514

Targeting the androgen receptor in triple-negative breast cancer.

PubMed

Gucalp, Ayca; Traina, Tiffany A

Triple-negative breast cancer represents approximately 15%-20% of all newly diagnosed breast cancers, but it accounts for a disproportionate number of breast cancer-related deaths each year. Owing to the lack of estrogen, progesterone, and human epidermal growth factor receptor 2 expression, patients with triple-negative breast cancer do not benefit from generally well-tolerated and effective therapies targeting the estrogen and human epidermal growth factor receptor 2 signaling pathways and are faced with an increased risk of disease progression and poorer overall survival. The heterogeneity of triple-negative breast cancer has been increasingly recognized and this may lead to therapeutic opportunities because of newly defined oncogenic drivers and targets. A subset of triple-negative breast tumors expresses the androgen receptor (AR) and this may benefit from treatments that inhibit the AR-signaling pathway. The first proof-of-concept trial established activity of the AR antagonist, bicalutamide, in patients with advanced AR+ triple-negative breast cancer. Since that time, evidence further supports the activity of other next-generation AR-targeted agents such as enzalutamide. Not unlike in estrogen receptor-positive breast cancer, mechanisms of resistance are being investigated and rationale exists for thoughtful, well-designed combination regimens such as AR antagonism with CDK4/6 pathway inhibitors or PI3K inhibitors. Furthermore, novel agents developed for the treatment of prostate cancer, which reduce androgen production such as abiraterone acetate and seviteronel, are being tested as well. This review summarizes the underlying biology of AR signaling in breast cancer development and the available clinical trial data for the use of anti-androgen therapy in the treatment of AR+ triple-negative breast cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

First-in-human study of PET and optical dual-modality image-guided surgery in glioblastoma using 68Ga-IRDye800CW-BBN.

PubMed

Li, Deling; Zhang, Jingjing; Chi, Chongwei; Xiao, Xiong; Wang, Junmei; Lang, Lixin; Ali, Iqbal; Niu, Gang; Zhang, Liwei; Tian, Jie; Ji, Nan; Zhu, Zhaohui; Chen, Xiaoyuan

2018-01-01

Purpose : Despite the use of fluorescence-guided surgery (FGS), maximum safe resection of glioblastoma multiforme (GBM) remains a major challenge. It has restricted surgeons between preoperative diagnosis and intraoperative treatment. Currently, an integrated approach combining preoperative assessment with intraoperative guidance would be a significant step in this direction. Experimental design : We developed a novel 68 Ga-IRDye800CW-BBN PET/near-infrared fluorescence (NIRF) dual-modality imaging probe targeting gastrin-releasing peptide receptor (GRPR) in GBM. The preclinical in vivo tumor imaging and FGS were first evaluated using an orthotopic U87MG glioma xenograft model. Subsequently, the first-in-human prospective cohort study (NCT 02910804) of GBM patients were conducted with preoperative PET assessment and intraoperative FGS. Results : The orthotopic tumors in mice could be precisely resected using the near-infrared intraoperative system. Translational cohort research in 14 GBM patients demonstrated an excellent correlation between preoperative positive PET uptake and intraoperative NIRF signal. The tumor fluorescence signals were significantly higher than those from adjacent brain tissue in vivo and ex vivo (p < 0.0001). Compared with pathology, the sensitivity and specificity of fluorescence using 42 loci of fluorescence-guided sampling were 93.9% (95% CI 79.8%-99.3%) and 100% (95% CI 66.4%-100%), respectively. The tracer was safe and the extent of resection was satisfactory without newly developed neurologic deficits. Progression-free survival (PFS) at 6 months was 80% and two newly diagnosed patients achieved long PFS. Conclusions: This initial study has demonstrated that the novel dual-modality imaging technique is feasible for integrated pre- and intraoperative targeted imaging via the same molecular receptor and improved intraoperative GBM visualization and maximum safe resection.

New diagnostic tool for robotic psychology and robotherapy studies.

PubMed

Libin, Elena; Libin, Alexander

2003-08-01

Robotic psychology and robotherapy as a new research area employs a systematic approach in studying psycho-physiological, psychological, and social aspects of person-robot communication. An analysis of the mechanisms underlying different forms of computer-mediated behavior requires both an adequate methodology and research tools. In the proposed article we discuss the concept, basic principles, structure, and contents of the newly designed Person-Robot Complex Interactive Scale (PRCIS), proposed for the purpose of investigating psychological specifics and therapeutic potentials of multilevel person-robot interactions. Assuming that human-robot communication has symbolic meaning, each interactive pattern evaluated via the newly developed scale is assigned certain psychological value associated with the person's past life experiences, likes and dislikes, emotional, cognitive, and behavioral traits or states. PRCIS includes (1) assessment of a person's individual style of communication with the robotic creature based on direct observations; (2) the participant's evaluation of his/her new experiences with an interactive robot and evaluation of its features, advantages and disadvantages, as well as past experiences with modern technology; and (3) the instructor's overall evaluation of the session.

Newly Recognized Mendelian Disorders with Rheumatic Manifestations

PubMed Central

de Jesus, Adriana Almeida; Goldbach-Mansky, Raphaela

2015-01-01

Summary A number of novel monogenic diseases that present with innate and/or acquired immune dysregulation reveal novel immune pathways that cause human inflammatory diseases and suggest novel targets for treatment. PMID:26196376

New benzimidazoles and their antitumor effects with Aurora A kinase and KSP inhibitory activities.

PubMed

Abd El-All, Amira S; Magd-El-Din, Asmaa A; Ragab, Fatma A F; ElHefnawi, Mahmoud; Abdalla, Mohamed M; Galal, Shadia A; El-Rashedy, Ahmed A

2015-07-01

A newly synthesized series of anticancer compounds comprising thiazolo[3,2-a]pyrimidine derivatives 6a-q bearing a benzimidazole moiety was produced via a one-pot reaction of N-(4-(1H-benzo[d]imidazol-2-yl)phenyl)-2-cyanoacetamide 5 with 2-aminothiazole and an appropriate aromatic aldehyde. Compound 7 was obtained via the reaction of 4-(1H-benzo[d]imidazol-2yl)benzenamide 1 with carbon disulphide and methyl iodide in the presence of concentrated aqueous solution of NaOH, then treated with o-phenylenediamine to give N-(4-1H-benzo[d]imidazol-2-yl)phenyl)-1H-benzo[d]imidazol-2-amine 8. The structures of the newly synthesized compounds were confirmed by analytical and spectroscopic measurements (IR, MS, and (1) H NMR). The synthesized products were screened and studied for their in vitro antitumor activity against three human cancer cell lines (namely colorectal cancer cell line HCT116, human liver cancer cell line HepG2, and human ovarian cancer cell line A2780) and their Aurora A kinase and KSP inhibitory activities. All newly synthesized compounds revealed marked results comparable with the standard drug CK0106023. The compounds 6e and 6k of the thiazolopyrimidine derivatives were the most active compounds when tested against the three cell lines in comparison with the standard drug CK0106023, and showed potent dual KSP and Aurora A kinase inhibition. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Adult human pancreas-derived cells expressing stage-specific embryonic antigen 4 differentiate into Sox9-expressing and Ngn3-expressing pancreatic ducts in vivo.

PubMed

Lee, Song; Lee, Chan Mi; Kim, Song Cheol

2016-11-11

Tissue-specific stem/progenitor cells are found in various adult tissues and may have the capacity for lineage-specific differentiation, facilitating applications in autologous transplantation. Stage-specific embryonic antigen 4 (SSEA-4), an early embryonic glycolipid antigen, is expressed in cells derived from adult human pancreas exocrine tissue. Here, we examined the characteristics and lineage-specific differentiation capacity of SSEA-4 + cells. Human adult partial pancreas tissues were obtained from different donors and cultured in vitro. SSEA-4 + and CA19-9 + cells were isolated from adult human pancreas exocrine cells using magnetic-activated cell sorting, and gene expression was validated by quantitative polymerase chain reaction. To confirm in-vivo differentiation, SSEA-4 + and CA19-9 + cells were transplanted into the dorsal subcutaneous region of mice. Finally, morphological features of differentiated areas were confirmed by immunostaining and morphometric analysis. SSEA-4-expressing cells were detected in isolated pancreas exocrine cells from adult humans. These SSEA-4 + cells exhibited coexpression of CA19-9, a marker of pancreatic duct cells, but not amylase expression, as shown by immunostaining and flow cytometry. SSEA-4 + cells exhibited higher relative expression of Oct4, Nanog, Klf4, Sox2, and c-Myc mRNAs than CA19-9 + cells. Pancreatic intralobular ducts (PIDs) were generated from SSEA-4 + or CA19-9 + cells in vivo at 5 weeks after transplantation. However, newly formed PIDs from CA19-9 + cells were less abundant and showed an incomplete PID morphology. In contrast, newly formed PIDs from SSEA-4 + cells were abundant in the transplanted area and showed a crowded morphology, typical of PIDs. Sox9 and Ngn3, key transcription factors associated with pancreatic development and regeneration, were expressed in PIDs from SSEA-4 + cells. SSEA-4-expressing cells in the adult human pancreas may have the potential for regeneration of the pancreas and may be used as a source of stem/progenitor cells for pancreatic cell lineage-specific differentiation.

Anthropogenic- and natural sources of dust in peatland during the Anthropocene

NASA Astrophysics Data System (ADS)

Fiałkiewicz-Kozieł, B.; Smieja-Król, B.; Frontasyeva, M.; Słowiński, M.; Marcisz, K.; Lapshina, E.; Gilbert, D.; Buttler, A.; Jassey, V. E. J.; Kaliszan, K.; Laggoun-Défarge, F.; Kołaczek, P.; Lamentowicz, M.

2016-12-01

As human impact have been increasing strongly over the last decades, it is crucial to distinguish human-induced dust sources from natural ones in order to define the boundary of a newly proposed epoch - the Anthropocene. Here, we track anthropogenic signatures and natural geochemical anomalies in the Mukhrino peatland, Western Siberia. Human activity was recorded there from cal AD 1958 (±6). Anthropogenic spheroidal aluminosilicates clearly identify the beginning of industrial development and are proposed as a new indicator of the Anthropocene. In cal AD 1963 (±5), greatly elevated dust deposition and an increase in REE serve to show that the geochemistry of elements in the peat can be evidence of nuclear weapon testing; such constituted an enormous force blowing soil dust into the atmosphere. Among the natural dust sources, minor signals of dryness and of the Tunguska cosmic body (TCB) impact were noted. The TCB impact was indirectly confirmed by an unusual occurrence of mullite in the peat.

Anthropogenic- and natural sources of dust in peatland during the Anthropocene

PubMed Central

Fiałkiewicz-Kozieł, B.; Smieja-Król, B.; Frontasyeva, M.; Słowiński, M.; Marcisz, K.; Lapshina, E.; Gilbert, D.; Buttler, A.; Jassey, V. E. J.; Kaliszan, K.; Laggoun-Défarge, F.; Kołaczek, P.; Lamentowicz, M.

2016-01-01

As human impact have been increasing strongly over the last decades, it is crucial to distinguish human-induced dust sources from natural ones in order to define the boundary of a newly proposed epoch - the Anthropocene. Here, we track anthropogenic signatures and natural geochemical anomalies in the Mukhrino peatland, Western Siberia. Human activity was recorded there from cal AD 1958 (±6). Anthropogenic spheroidal aluminosilicates clearly identify the beginning of industrial development and are proposed as a new indicator of the Anthropocene. In cal AD 1963 (±5), greatly elevated dust deposition and an increase in REE serve to show that the geochemistry of elements in the peat can be evidence of nuclear weapon testing; such constituted an enormous force blowing soil dust into the atmosphere. Among the natural dust sources, minor signals of dryness and of the Tunguska cosmic body (TCB) impact were noted. The TCB impact was indirectly confirmed by an unusual occurrence of mullite in the peat. PMID:27995953

Computer-based prediction of mitochondria-targeting peptides.

PubMed

Martelli, Pier Luigi; Savojardo, Castrense; Fariselli, Piero; Tasco, Gianluca; Casadio, Rita

2015-01-01

Computational methods are invaluable when protein sequences, directly derived from genomic data, need functional and structural annotation. Subcellular localization is a feature necessary for understanding the protein role and the compartment where the mature protein is active and very difficult to characterize experimentally. Mitochondrial proteins encoded on the cytosolic ribosomes carry specific patterns in the precursor sequence from where it is possible to recognize a peptide targeting the protein to its final destination. Here we discuss to which extent it is feasible to develop computational methods for detecting mitochondrial targeting peptides in the precursor sequences and benchmark our and other methods on the human mitochondrial proteins endowed with experimentally characterized targeting peptides. Furthermore, we illustrate our newly implemented web server and its usage on the whole human proteome in order to infer mitochondrial targeting peptides, their cleavage sites, and whether the targeting peptide regions contain or not arginine-rich recurrent motifs. By this, we add some other 2,800 human proteins to the 124 ones already experimentally annotated with a mitochondrial targeting peptide.

Dynamic transcriptional signatures and network responses for clinical symptoms in influenza-infected human subjects using systems biology approaches.

PubMed

Linel, Patrice; Wu, Shuang; Deng, Nan; Wu, Hulin

2014-10-01

Recent studies demonstrate that human blood transcriptional signatures may be used to support diagnosis and clinical decisions for acute respiratory viral infections such as influenza. In this article, we propose to use a newly developed systems biology approach for time course gene expression data to identify significant dynamically response genes and dynamic gene network responses to viral infection. We illustrate the methodological pipeline by reanalyzing the time course gene expression data from a study with healthy human subjects challenged by live influenza virus. We observed clear differences in the number of significant dynamic response genes (DRGs) between the symptomatic and asymptomatic subjects and also identified DRG signatures for symptomatic subjects with influenza infection. The 505 common DRGs shared by the symptomatic subjects have high consistency with the signature genes for predicting viral infection identified in previous works. The temporal response patterns and network response features were carefully analyzed and investigated.

Estimation of the absorption coefficients of two-layered media by a simple method using spatially and time-resolved reflectances

NASA Astrophysics Data System (ADS)

Shimada, M.; Sato, C.; Hoshi, Y.; Yamada, Y.

2009-08-01

Our newly developed method using spatially and time-resolved reflectances can easily estimate the absorption coefficients of each layer in a two-layered medium if the thickness of the upper layer and the reduced scattering coefficients of the two layers are known a priori. We experimentally validated this method using phantoms and examined its possibility of estimating the absorption coefficients of the tissues in human heads. In the case of a homogeneous plastic phantom (polyacetal block), the absorption coefficient estimated by our method agreed well with that obtained by a conventional method. Also, in the case of two-layered phantoms, our method successfully estimated the absorption coefficients of the two layers. Furthermore, the absorption coefficients of the extracerebral and cerebral tissue inside human foreheads were estimated under the assumption that the human heads were two-layered media. It was found that the absorption coefficients of the cerebral tissues were larger than those of the extracerebral tissues.

Tumor dosimetry for I-131 trastuzumab therapy in a Her2+ NCI N87 xenograft mouse model using the Siemens SYMBIA E gamma camera with a pinhole collimator

NASA Astrophysics Data System (ADS)

Lee, Young Sub; Kim, Jin Su; Deuk Cho, Kyung; Kang, Joo Hyun; Moo Lim, Sang

2015-07-01

We performed imaging and therapy using I-131 trastuzumab and a pinhole collimator attached to a conventional gamma camera for human use in a mouse model. The conventional clinical gamma camera with a 2-mm radius-sized pinhole collimator was used for monitoring the animal model after administration of I-131 trastuzumab The highest and lowest radiation-received organs were osteogenic cells (0.349 mSv/MBq) and skin (0.137 mSv/MBq), respectively. The mean coefficients of variation (%CV) of the effective dose equivalent and effective dose were 0.091 and 0.093 mSv/MBq respectively. We showed the feasibility of the pinholeattached conventional gamma camera for human use for the assessment of dosimetry. Mouse dosimetry and prediction of human dosimetry could be used to provide data for the safety and efficacy of newly developed therapeutic schemes.

Anthropogenic- and natural sources of dust in peatland during the Anthropocene.

PubMed

Fiałkiewicz-Kozieł, B; Smieja-Król, B; Frontasyeva, M; Słowiński, M; Marcisz, K; Lapshina, E; Gilbert, D; Buttler, A; Jassey, V E J; Kaliszan, K; Laggoun-Défarge, F; Kołaczek, P; Lamentowicz, M

2016-12-20

As human impact have been increasing strongly over the last decades, it is crucial to distinguish human-induced dust sources from natural ones in order to define the boundary of a newly proposed epoch - the Anthropocene. Here, we track anthropogenic signatures and natural geochemical anomalies in the Mukhrino peatland, Western Siberia. Human activity was recorded there from cal AD 1958 (±6). Anthropogenic spheroidal aluminosilicates clearly identify the beginning of industrial development and are proposed as a new indicator of the Anthropocene. In cal AD 1963 (±5), greatly elevated dust deposition and an increase in REE serve to show that the geochemistry of elements in the peat can be evidence of nuclear weapon testing; such constituted an enormous force blowing soil dust into the atmosphere. Among the natural dust sources, minor signals of dryness and of the Tunguska cosmic body (TCB) impact were noted. The TCB impact was indirectly confirmed by an unusual occurrence of mullite in the peat.

The novel JNK inhibitor AS602801 inhibits cancer stem cells in vitro and in vivo.

PubMed

Okada, Masashi; Kuramoto, Kenta; Takeda, Hiroyuki; Watarai, Hikaru; Sakaki, Hirotsugu; Seino, Shizuka; Seino, Manabu; Suzuki, Shuhei; Kitanaka, Chifumi

2016-05-10

A phase 2 clinical trial investigating the efficacy and safety of AS602801, a newly developed JNK inhibitor, in the treatment of inflammatory endometriosis is complete. We are now examining whether AS602801 acts against human cancer cells in vitro and in vivo. In vitro, AS602801 exhibited cytotoxicity against both serum-cultured non-stem cancer cells and cancer stem cells derived from human pancreatic cancer, non-small cell lung cancer, ovarian cancer and glioblastoma at concentrations that did not decrease the viability of normal human fibroblasts. AS602801 also inhibited the self-renewal and tumor-initiating capacity of cancer stem cells surviving AS602801 treatment. Cancer stem cells in established xenograft tumors were reduced by systemic administration of AS602801 at a dose and schedule that did not adversely affect the health of the tumor-bearing mice. These findings suggest AS602801 is a promising anti-cancer stem cell agent, and further investigation of the utility of AS602801 in the treatment of cancer seems warranted.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ying, Tianlei; Prabakaran, Ponraj; Du, Lanying

The MERS-CoV is an emerging virus, which already infected more than 1,300 humans with high (~36%) mortality. Here, we show that m336, an exceptionally potent human anti-MERS-CoV antibody, is almost germline with only one somatic mutation in the heavy chain. The structure of Fab m336 in complex with the MERS-CoV receptor-binding domain reveals that its IGHV1-69-derived heavy chain provides more than 85% binding surface and that its epitope almost completely overlaps with the receptor-binding site. Analysis of antibodies from 69 healthy humans suggests an important role of the V(D)J recombination-generated junctional and allele-specific residues for achieving high affinity of bindingmore » at such low levels of somatic hypermutation. Our results also have important implications for development of vaccine immunogens based on the newly identified m336 epitope as well as for elucidation of mechanisms of neutralization by m336-like antibodies and their elicitation in vivo.« less

HUNT: launch of a full-length cDNA database from the Helix Research Institute.

PubMed

Yudate, H T; Suwa, M; Irie, R; Matsui, H; Nishikawa, T; Nakamura, Y; Yamaguchi, D; Peng, Z Z; Yamamoto, T; Nagai, K; Hayashi, K; Otsuki, T; Sugiyama, T; Ota, T; Suzuki, Y; Sugano, S; Isogai, T; Masuho, Y

2001-01-01

The Helix Research Institute (HRI) in Japan is releasing 4356 HUman Novel Transcripts and related information in the newly established HUNT database. The institute is a joint research project principally funded by the Japanese Ministry of International Trade and Industry, and the clones were sequenced in the governmental New Energy and Industrial Technology Development Organization (NEDO) Human cDNA Sequencing Project. The HUNT database contains an extensive amount of annotation from advanced analysis and represents an essential bioinformatics contribution towards understanding of the gene function. The HRI human cDNA clones were obtained from full-length enriched cDNA libraries constructed with the oligo-capping method and have resulted in novel full-length cDNA sequences. A large fraction has little similarity to any proteins of known function and to obtain clues about possible function we have developed original analysis procedures. Any putative function deduced here can be validated or refuted by complementary analysis results. The user can also extract information from specific categories like PROSITE patterns, PFAM domains, PSORT localization, transmembrane helices and clones with GENIUS structure assignments. The HUNT database can be accessed at http://www.hri.co.jp/HUNT.

Identification and Application of Neutralizing Epitopes of Human Adenovirus Type 55 Hexon Protein

PubMed Central

Tian, Xingui; Ma, Qiang; Jiang, Zaixue; Huang, Junfeng; Liu, Qian; Lu, Xiaomei; Luo, Qingming; Zhou, Rong

2015-01-01

Human adenovirus type 55 (HAdV55) is a newly identified re-emergent acute respiratory disease (ARD) pathogen with a proposed recombination of hexon gene between HAdV11 and HAdV14 strains. The identification of the neutralizing epitopes is important for the surveillance and vaccine development against HAdV55 infection. In this study, four type-specific epitope peptides of HAdV55 hexon protein, A55R1 (residues 138 to 152), A55R2 (residues 179 to 187), A55R4 (residues 247 to 259) and A55R7 (residues 429 to 443), were predicted by multiple sequence alignment and homology modeling methods, and then confirmed with synthetic peptides by enzyme-linked immunosorbent assay (ELISA) and neutralization tests (NT). Finally, the A55R2 was incorporated into human adenoviruses 3 (HAdV3) and a chimeric adenovirus rAd3A55R2 was successfully obtained. The chimeric rAd3A55R2 could induce neutralizing antibodies against both HAdV3 and HAdV55. This current study will contribute to the development of novel adenovirus vaccine candidate and adenovirus structural analysis. PMID:26516903

Novel Biodegradable Porous Scaffold Applied to Skin Regeneration

PubMed Central

Wang, Hui-Min; Chou, Yi-Ting; Wen, Zhi-Hong; Wang, Zhao-Ren; Chen, Chun-Hong; Ho, Mei-Ling

2013-01-01

Skin wound healing is an important lifesaving issue for massive lesions. A novel porous scaffold with collagen, hyaluronic acid and gelatin was developed for skin wound repair. The swelling ratio of this developed scaffold was assayed by water absorption capacity and showed a value of over 20 g water/g dried scaffold. The scaffold was then degraded in time- and dose-dependent manners by three enzymes: lysozyme, hyaluronidase and collagenase I. The average pore diameter of the scaffold was 132.5±8.4 µm measured from SEM images. With human skin cells growing for 7 days, the SEM images showed surface fractures on the scaffold due to enzymatic digestion, indicating the biodegradable properties of this scaffold. To simulate skin distribution, the human epidermal keratinocytes, melanocytes and dermal fibroblasts were seeded on the porous scaffold and the cross-section immunofluorescent staining demonstrated normal human skin layer distributions. The collagen amount was also quantified after skin cells seeding and presented an amount 50% higher than those seeded on culture wells. The in vivo histological results showed that the scaffold ameliorated wound healing, including decreasing neutrophil infiltrates and thickening newly generated skin compared to the group without treatments. PMID:23762223

Chemical Computer Man: Chemical Agent Response Simulation (CARS). Technical report, January 1983-September 1985

DOE Office of Scientific and Technical Information (OSTI.GOV)

Davis, E.G.; Mioduszewski, R.J.

The Chemical Computer Man: Chemical Agent Response Simulation (CARS) is a computer model and simulation program for estimating the dynamic changes in human physiological dysfunction resulting from exposures to chemical-threat nerve agents. The newly developed CARS methodology simulates agent exposure effects on the following five indices of human physiological function: mental, vision, cardio-respiratory, visceral, and limbs. Mathematical models and the application of basic pharmacokinetic principles were incorporated into the simulation so that for each chemical exposure, the relationship between exposure dosage, absorbed dosage (agent blood plasma concentration), and level of physiological response are computed as a function of time. CARS,more » as a simulation tool, is designed for the users with little or no computer-related experience. The model combines maximum flexibility with a comprehensive user-friendly interactive menu-driven system. Users define an exposure problem and obtain immediate results displayed in tabular, graphical, and image formats. CARS has broad scientific and engineering applications, not only in technology for the soldier in the area of Chemical Defense, but also in minimizing animal testing in biomedical and toxicological research and the development of a modeling system for human exposure to hazardous-waste chemicals.« less

Integration of immunological aspects in the European Human Embryonic Stem Cell Registry.

PubMed

Borstlap, Joeri; Kurtz, Andreas

2008-05-01

The immunological properties of stem cells are of increasing importance in regenerative medicine. Immunomodulatory mechanisms seem to play an important role not only with respect to the understanding of underlying mechanisms of autologous versus allogenic therapeutic approaches, but also for endogeneous tissue regeneration. The newly established European human embryonic stem cell registry (hESCreg) offers an international database for the registration, documentation and characterisation of human embryonic stem cells (hESC) and their use. By doing so, hESCreg aims to develop a model procedure for further standardisation efforts in the field of stem cell research and regenerative medicine, and eventually the registry may lead to a repository of therapy-related information. Currently the stem cell characterisation data acquired by the registry are divided into several categories such as cell derivation, culture conditions, genetic constitution, stem cell marker expression and degree of modification. This article describes immunological aspects of stem cell characterisation and explores the layout and relevance of a possible additional section to the hESCreg repository to include immunological characteristics of human embryonic stem cells.

Are We Prepared in Case of a Possible Smallpox-Like Disease Emergence?

PubMed Central

Olson, Victoria A.; Shchelkunov, Sergei N.

2017-01-01

Smallpox was the first human disease to be eradicated, through a concerted vaccination campaign led by the World Health Organization. Since its eradication, routine vaccination against smallpox has ceased, leaving the world population susceptible to disease caused by orthopoxviruses. In recent decades, reports of human disease from zoonotic orthopoxviruses have increased. Furthermore, multiple reports of newly identified poxviruses capable of causing human disease have occurred. These facts raise concerns regarding both the opportunity for these zoonotic orthopoxviruses to evolve and become a more severe public health issue, as well as the risk of Variola virus (the causative agent of smallpox) to be utilized as a bioterrorist weapon. The eradication of smallpox occurred prior to the development of the majority of modern virological and molecular biological techniques. Therefore, there is a considerable amount that is not understood regarding how this solely human pathogen interacts with its host. This paper briefly recounts the history and current status of diagnostic tools, vaccines, and anti-viral therapeutics for treatment of smallpox disease. The authors discuss the importance of further research to prepare the global community should a smallpox-like virus emerge.

Probiotics, antibiotics and the immune responses to vaccines

PubMed Central

Praharaj, Ira; John, Sushil M.; Bandyopadhyay, Rini; Kang, Gagandeep

2015-01-01

Orally delivered vaccines have been shown to perform poorly in developing countries. There are marked differences in the structure and the luminal environment of the gut in developing countries resulting in changes in immune and barrier function. Recent studies using newly developed technology and analytic methods have made it increasingly clear that the intestinal microbiota activate a multitude of pathways that control innate and adaptive immunity in the gut. Several hypotheses have been proposed for the underperformance of oral vaccines in developing countries, and modulation of the intestinal microbiota is now being tested in human clinical trials. Supplementation with specific strains of probiotics has been shown to have modulatory effects on intestinal and systemic immune responses in animal models and forms the basis for human studies with vaccines. However, most studies published so far that have evaluated the immune response to vaccines in children and adults have been small and results have varied by age, antigen, type of antibody response and probiotic strain. Use of anthelminthic drugs in children has been shown to possibly increase immunogenicity following oral cholera vaccination, lending further support to the rationale for modulation of the immune response to oral vaccination through the intestinal microbiome. PMID:25964456

In vivo cell biology in zebrafish – providing insights into vertebrate development and disease

PubMed Central

Vacaru, Ana M.; Unlu, Gokhan; Spitzner, Marie; Mione, Marina; Knapik, Ela W.; Sadler, Kirsten C.

2014-01-01

ABSTRACT Over the past decades, studies using zebrafish have significantly advanced our understanding of the cellular basis for development and human diseases. Zebrafish have rapidly developing transparent embryos that allow comprehensive imaging of embryogenesis combined with powerful genetic approaches. However, forward genetic screens in zebrafish have generated unanticipated findings that are mirrored by human genetic studies: disruption of genes implicated in basic cellular processes, such as protein secretion or cytoskeletal dynamics, causes discrete developmental or disease phenotypes. This is surprising because many processes that were assumed to be fundamental to the function and survival of all cell types appear instead to be regulated by cell-specific mechanisms. Such discoveries are facilitated by experiments in whole animals, where zebrafish provides an ideal model for visualization and manipulation of organelles and cellular processes in a live vertebrate. Here, we review well-characterized mutants and newly developed tools that underscore this notion. We focus on the secretory pathway and microtubule-based trafficking as illustrative examples of how studying cell biology in vivo using zebrafish has broadened our understanding of the role fundamental cellular processes play in embryogenesis and disease. PMID:24481493

The overexpressed human 46-kDa mannose 6-phosphate receptor mediates endocytosis and sorting of. beta. -glucuronidase

DOE Office of Scientific and Technical Information (OSTI.GOV)

Watanabe, H.; Grubb, J.H.; Sly, W.S.

1990-10-01

The authors studied the function of the human small (46-kDa) mannose 6-phosphate receptor (SMPR) in transfected mouse L cells that do not express the larger insulin-like growth factor II/mannose 6-phosphate receptor. Cells overexpressing human SMPR were studied for enzyme binding to cell surface receptors, for binding to intracellular receptors in permeabilized cells, and for receptor-mediated endocytosis of recombinant human {beta}-glucuronidase. Specific binding to human SMPR in permeabilized cells showed a pH optimum between pH 6.0 and pH 6.5. Binding was significant in the present of EDTA but was enhanced by added divalent cations. Up to 2.3{percent} of the total functionalmore » receptor could be detected on the cell surface by enzyme binding. They present experiments showing that at very high levels of overexpression, and at pH 6.5, human SMPR mediated the endocytosis of {beta}-glucuronidase. At pH 7.5, the rate of endocytosis was only 14{percent} the rate seen at pH 6.5. Cells overexpressing human SMPR also showed reduced secretion of newly synthesized {beta}-glucuronidase when compared to cells transfected with vector only, suggesting that overexpressed human SMPR can participate in sorting of newly synthesized {beta}-glucuronidase and partially correct the sorting defect in mouse L cells that do not express the insulin-like growth factor II/mannose 6-phosphate receptor.« less

76 FR 33419 - Nationally Recognized Statistical Rating Organizations

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-08

... documentation of the internal control structure) or should the factors focus on the design (i.e., establishment... related to implementing them. a. Controls reasonably designed to ensure that a newly developed methodology... U.S.C. 78o-7(r)(1)(A). b. Controls reasonably designed to ensure that a newly developed methodology...

The Spelling Project. Technical Report 1992-2.

ERIC Educational Resources Information Center

Green, Kathy E.; Schroeder, David H.

Results of an analysis of a newly developed spelling test and several related measures are reported. Information about the reliability of a newly developed spelling test; its distribution of scores; its relationship with the standard battery of aptitude tests of the Johnson O'Connor Research Foundation; and its relationships with sex, age,…

How Schools Can Promote Healthy Development for Newly Arrived Immigrant and Refugee Adolescents: Research Priorities

ERIC Educational Resources Information Center

McNeely, Clea A.; Morland, Lyn; Doty, S. Benjamin; Meschke, Laurie L.; Awad, Summer; Husain, Altaf; Nashwan, Ayat

2017-01-01

Background: The US education system must find creative and effective ways to foster the healthy development of the approximately 2 million newly arrived immigrant and refugee adolescents, many of whom contend with language barriers, limited prior education, trauma, and discrimination. We identify research priorities for promoting the school…

Practices influenced by policy? An exploration of newly hired science teachers at sites in South Africa and the United States

NASA Astrophysics Data System (ADS)

Navy, S. L.; Luft, J. A.; Toerien, R.; Hewson, P. W.

2018-05-01

In many parts of the world, newly hired science teachers' practices are developing in a complex policy environment. However, little is known about how newly hired science teachers' practices are enacted throughout a cycle of instruction and how these practices can be influenced by macro-, meso-, and micro-policies. Knowing how policies impact practice can result in better policies or better support for certain policies in order to enhance the instruction of newly hired teachers. This comparative study investigated how 12 newly hired science teachers at sites in South Africa (SA) and the United States (US) progressed through an instructional cycle of planning, teaching, and reflection. The qualitative data were analysed through beginning teacher competency frameworks, the cycle of instruction, and institutional theory. Data analysis revealed prevailing areas of practice and connections to levels of policy within the instructional cycle phases. There were some differences between the SA and US teachers and among first-, second-, and third-year teachers. More importantly, this study indicates that newly hired teachers are susceptible to micro-policies and are progressively developing their practice. It also shows the importance of meso-level connectors. It suggests that teacher educators and policy makers must consider how to prepare and support newly hired science teachers to achieve the shared global visions of science teaching.

Construction and characterization of human oral mucosa equivalent using hyper-dry amniotic membrane as a matrix.

PubMed

Qi, Fangfang; Yoshida, Toshiko; Koike, Takeshi; Aizawa, Hitoshi; Shimane, Tetsu; Li, Yinghui; Yamada, Shinichi; Okabe, Motonori; Nikaido, Toshio; Kurita, Hiroshi

2016-05-01

Human amniotic membrane(HAM) as a graft material has been used in various fields. Hyper-dry amniotic membrane (HD-AM) is a novel dried amniotic membrane that is easy to handle and can be preserved at room temperature without time limitation. The purpose of this study was to investigate the useful properties of HD-AM in reconstruction of the oral mucosa. Human oral keratinocytes were isolated and seeded on HD-AM in serum-free culture system. Oral mucosa equivalent (OME) was developed and transplanted onto full-thickness wound on athymic mice. The wound healing was analyzed and the OME both before and after transplantation was analyzed with hematoxylin-eosin staining and immunohistochemical staining for Cytokines 10 (CK10), Cytokines 16 (CK16), and Ivolucrin (IVL). Oral keratinocytes spread and proliferated well on HD-AM. Two weeks after air-lifting, OME had formed with good differentiation and morphology. We confirmed immunohistochemically that the expression of CK10 was positive in all suprabasal layers, as was CK16 in the upper layers, while IVL was present in all cell layers. Three weeks after transplantation to athymic mice, the newly generated tissue had survived well with the smallest contraction. The epithelial cells of newly generated tissue expressed CK10 throughout in all suprabasal layers, IVL was mainly in the granular layer, and CK16 positive cells were observed in all spinous layer and granular layer but were not expressed in the mouse skin, all of which were similar to native gingival mucosa. The OME with HD-AM as a matrix revealed a good morphology and stable wound healing. This study demonstrates that HD-AM is a useful and feasible biomaterial for oral mucosa reconstruction. Copyright © 2016 Elsevier Ltd. All rights reserved.

Presence of broadly reactive and group-specific neutralizing epitopes on newly described isolates of Crimean-Congo hemorrhagic fever virus.

PubMed

Ahmed, Asim A; McFalls, Jeanne M; Hoffmann, Christian; Filone, Claire Marie; Stewart, Shaun M; Paragas, Jason; Khodjaev, Shabot; Shermukhamedova, Dilbar; Schmaljohn, Connie S; Doms, Robert W; Bertolotti-Ciarlet, Andrea

2005-12-01

Crimean-Congo hemorrhagic fever virus (CCHFV), a member of the genus Nairovirus of the family Bunyaviridae, causes severe disease in humans with high rates of mortality. The virus has a tripartite genome composed of a small (S), a medium (M) and a large (L) RNA segment; the M segment encodes the two viral glycoproteins, G(N) and G(C). Whilst relatively few full-length M segment sequences are available, it is apparent that both G(N) and G(C) may exhibit significant sequence diversity. It is unknown whether considerable antigenic differences exist between divergent CCHFV strains, or whether there are conserved neutralizing epitopes. The M segments derived from viral isolates of a human case of CCHF in South Africa (SPU 41/84), an infected tick (Hyalomma marginatum) in South Africa (SPU 128/81), a human case in Congo (UG 3010), an infected individual in Uzbekistan (U2-2-002) and an infected tick (Hyalomma asiaticum) in China (Hy13) were sequenced fully, and the glycoproteins were expressed. These novel sequences showed high variability in the N-terminal region of G(N) and more modest differences in the remainder of G(N) and in G(C). Phylogenetic analyses placed these newly identified strains in three of the four previously described M segment groups. Studies with a panel of mAbs specific to G(N) and G(C) indicated that there were significant antigenic differences between the M segment groups, although several neutralizing epitopes in both G(N) and G(C) were conserved among all strains examined. Thus, the genetic diversity exhibited by CCHFV strains results in significant antigenic differences that will need to be taken into consideration for vaccine development.

Virtual Habitat -a dynamic simulation of closed life support systems -human model status

NASA Astrophysics Data System (ADS)

Markus Czupalla, M. Sc.; Zhukov, Anton; Hwang, Su-Au; Schnaitmann, Jonas

In order to optimize Life Support Systems on a system level, stability questions must be in-vestigated. To do so the exploration group of the Technical University of Munich (TUM) is developing the "Virtual Habitat" (V-HAB) dynamic LSS simulation software. V-HAB shall provide the possibility to conduct dynamic simulations of entire mission scenarios for any given LSS configuration. The Virtual Habitat simulation tool consists of four main modules: • Closed Environment Module (CEM) -monitoring of compounds in a closed environment • Crew Module (CM) -dynamic human simulation • P/C Systems Module (PCSM) -dynamic P/C subsystems • Plant Module (PM) -dynamic plant simulation The core module of the simulation is the dynamic and environment sensitive human module. Introduced in its basic version in 2008, the human module has been significantly updated since, increasing its capabilities and maturity significantly. In this paper three newly added human model subsystems (thermal regulation, digestion and schedule controller) are introduced touching also on the human stress subsystem which is cur-rently under development. Upon the introduction of these new subsystems, the integration of these into the overall V-HAB human model is discussed, highlighting the impact on the most important I/F. The overall human model capabilities shall further be summarized and presented based on meaningful test cases. In addition to the presentation of the results, the correlation strategy for the Virtual Habitat human model shall be introduced assessing the models current confidence level and giving an outlook on the future correlation strategy. Last but not least, the remaining V-HAB mod-ules shall be introduced shortly showing how the human model is integrated into the overall simulation.

Assessing Forelimb Function after Unilateral Cervical SCI using Novel Tasks: Limb Step-alternation, Postural Instability and Pasta Handling

PubMed Central

Schallert, Timothy; Schmidt, Christine E.

2013-01-01

Cervical spinal cord injury (cSCI) can cause devastating neurological deficits, including impairment or loss of upper limb and hand function. A majority of the spinal cord injuries in humans occur at the cervical levels. Therefore, developing cervical injury models and developing relevant and sensitive behavioral tests is of great importance. Here we describe the use of a newly developed forelimb step-alternation test after cervical spinal cord injury in rats. In addition, we describe two behavioral tests that have not been used after spinal cord injury: a postural instability test (PIT), and a pasta-handling test. All three behavioral tests are highly sensitive to injury and are easy to use. Therefore, we feel that these behavioral tests can be instrumental in investigating therapeutic strategies after cSCI. PMID:24084700

Assessing forelimb function after unilateral cervical SCI using novel tasks: limb step-alternation, postural instability and pasta handling.

PubMed

Khaing, Zin Z; Geissler, Sydney A; Schallert, Timothy; Schmidt, Christine E

2013-09-16

Cervical spinal cord injury (cSCI) can cause devastating neurological deficits, including impairment or loss of upper limb and hand function. A majority of the spinal cord injuries in humans occur at the cervical levels. Therefore, developing cervical injury models and developing relevant and sensitive behavioral tests is of great importance. Here we describe the use of a newly developed forelimb step-alternation test after cervical spinal cord injury in rats. In addition, we describe two behavioral tests that have not been used after spinal cord injury: a postural instability test (PIT), and a pasta-handling test. All three behavioral tests are highly sensitive to injury and are easy to use. Therefore, we feel that these behavioral tests can be instrumental in investigating therapeutic strategies after cSCI.

Zebrafish: A Model for the Study of Toxicants Affecting Muscle Development and Function

PubMed Central

Dubińska-Magiera, Magda; Daczewska, Małgorzata; Lewicka, Anna; Migocka-Patrzałek, Marta; Niedbalska-Tarnowska, Joanna; Jagla, Krzysztof

2016-01-01

The rapid progress in medicine, agriculture, and allied sciences has enabled the development of a large amount of potentially useful bioactive compounds, such as drugs and pesticides. However, there is another side of this phenomenon, which includes side effects and environmental pollution. To avoid or minimize the uncontrollable consequences of using the newly developed compounds, researchers seek a quick and effective means of their evaluation. In achieving this goal, the zebrafish (Danio rerio) has proven to be a highly useful tool, mostly because of its fast growth and development, as well as the ability to absorb the molecules diluted in water through its skin and gills. In this review, we focus on the reports concerning the application of zebrafish as a model for assessing the impact of toxicants on skeletal muscles, which share many structural and functional similarities among vertebrates, including zebrafish and humans. PMID:27869769

77 FR 31326 - Notice of Availability of a Final Supplemental Environmental Impact Statement for Replacement of...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-25

... demolition activities, substantial excavation and grading, installation of a geohazard soil stabilization... human environment. The No-Action Alternative was analyzed and assumes the newly proposed actions would...

Cross-protection of newly emerging HPAI H5 viruses by neutralizing human monoclonal antibodies: A viable alternative to oseltamivir.

PubMed

Ren, Huanhuan; Wang, Guiqin; Wang, Shuangshuang; Chen, Honglin; Chen, Zhiwei; Hu, Hongxing; Cheng, Genhong; Zhou, Paul

2016-01-01

Newly emerging highly pathogenic avian influenza (HPAI) H5N2, H5N3, H5N5, H5N6, H5N8 and H5N9 viruses have been spreading in poultry and wild birds. The H5N6 viruses have also caused 10 human infections with 4 fatal cases in China. Here, we assessed the cross-neutralization and cross-protection of human and mouse monoclonal antibodies against 2 viruses: a HPAI H5N8 virus, A/chicken/Netherlands/14015526/2014 (NE14) and a HPAI H5N6 virus, A/Sichuan/26221/2014 (SC14). The former was isolated from an infected chicken in Netherlands in 2014 and the latter was isolated from an infected human patient in Sichuan, China. We show that antibodies FLA5.10, FLD21.140, 100F4 and 65C6, but not AVFluIgG01, AVFluIgG03, S139/1 and the VRC01 control, potently cross-neutralize the H5N8 NE14 and H5N6 SC14 viruses. Furthermore, we show that a single injection of >1 mg/kg of antibody 100F4 at 4 hours before, or 20 mg/kg antibody 100F4 at 72 hours after, a lethal dose of H5N8 NE14 enables mice to withstand the infection. Finally, we show that a single injection of 0.5 or 1 mg/kg antibody 100F4 prophylactically or 10 mg/kg 100F4 therapeutically outperforms a 5-day course of 10 mg/kg/day oseltamivir treatment against lethal H5N8 NE14 or H5N6 SC14 infection in mice. Our results suggest that further preclinical evaluation of human monoclonal antibodies against newly emerging H5 viruses is warranted.

Cross-protection of newly emerging HPAI H5 viruses by neutralizing human monoclonal antibodies: A viable alternative to oseltamivir

PubMed Central

Ren, Huanhuan; Wang, Guiqin; Wang, Shuangshuang; Chen, Honglin; Chen, Zhiwei; Hu, Hongxing; Cheng, Genhong; Zhou, Paul

2016-01-01

ABSTRACT Newly emerging highly pathogenic avian influenza (HPAI) H5N2, H5N3, H5N5, H5N6, H5N8 and H5N9 viruses have been spreading in poultry and wild birds. The H5N6 viruses have also caused 10 human infections with 4 fatal cases in China. Here, we assessed the cross-neutralization and cross-protection of human and mouse monoclonal antibodies against 2 viruses: a HPAI H5N8 virus, A/chicken/Netherlands/14015526/2014 (NE14) and a HPAI H5N6 virus, A/Sichuan/26221/2014 (SC14). The former was isolated from an infected chicken in Netherlands in 2014 and the latter was isolated from an infected human patient in Sichuan, China. We show that antibodies FLA5.10, FLD21.140, 100F4 and 65C6, but not AVFluIgG01, AVFluIgG03, S139/1 and the VRC01 control, potently cross-neutralize the H5N8 NE14 and H5N6 SC14 viruses. Furthermore, we show that a single injection of >1 mg/kg of antibody 100F4 at 4 hours before, or 20 mg/kg antibody 100F4 at 72 hours after, a lethal dose of H5N8 NE14 enables mice to withstand the infection. Finally, we show that a single injection of 0.5 or 1 mg/kg antibody 100F4 prophylactically or 10 mg/kg 100F4 therapeutically outperforms a 5-day course of 10 mg/kg/day oseltamivir treatment against lethal H5N8 NE14 or H5N6 SC14 infection in mice. Our results suggest that further preclinical evaluation of human monoclonal antibodies against newly emerging H5 viruses is warranted. PMID:27167234

Practices Influenced by Policy? An Exploration of Newly Hired Science Teachers at Sites in South Africa and the United States

ERIC Educational Resources Information Center

Navy, S. L.; Luft, J. A.; Toerien, R.; Hewson, P. W.

2018-01-01

In many parts of the world, newly hired science teachers' practices are developing in a complex policy environment. However, little is known about how newly hired science teachers' practices are enacted throughout a cycle of instruction and how these practices can be influenced by macro-, meso-, and micro-policies. Knowing how policies impact…

Gen-27, a newly synthesized flavonoid, inhibits glycolysis and induces cell apoptosis via suppression of hexokinase II in human breast cancer cells.

PubMed

Tao, Lei; Wei, Libing; Liu, Yishi; Ding, Yang; Liu, Xiuting; Zhang, Xin; Wang, Xiaoping; Yao, Yuyuan; Lu, Jinrong; Wang, Qing; Hu, Rong

2017-02-01

We have previously reported that Gen-27, a newly synthesized flavonoid, exhibits anticancer effects against human colorectal cancer cells. In this study, we investigated the anticancer effects in human breast cancer cell lines and its underlying mechanisms. We demonstrated that Gen-27 inhibited the growth and proliferation of human breast cancer cells in concentration and time-dependent manners. It was found that Gen-27 induced mitochondrial-mediated apoptosis, characterized by the dissipation of mitochondrial membrane potential (ΔΨm), cytochrome c (Cyt c) release from mitochondria to cytosol, activation of caspases and induction of poly (ADP-ribose) polymerase (PARP). In addition, Gen-27 inhibited the glycolysis in human breast cancer cells. After treatment with Gen-27, the expression of HKII was down-regulated, accompanied by weakened interaction of HKII and VDAC. Further research revealed that the induction of mitochondrial apoptosis was associated with the decrease of HKII expression by Gen-27. Finally, in vivo studies demonstrated that Gen-27 significantly suppressed the growth and promoted apoptosis of MDA-MB-231 breast cancer orthotopic tumors with low systemic toxicity. In conclusion, the results showed that Gen-27 had significant anticancer effects against human breast cancer and it may potentially be used as a novel anticancer agent for the treatment of breast cancer. Copyright © 2016. Published by Elsevier Inc.

TRAP-Positive Multinucleated Giant Cells Are Foreign Body Giant Cells Rather Than Osteoclasts: Results From a Split-Mouth Study in Humans.

PubMed

Lorenz, Jonas; Kubesch, Alica; Korzinskas, Tadas; Barbeck, Mike; Landes, Constantin; Sader, Robert A; Kirkpatrick, Charles J; Ghanaati, Shahram

2015-12-01

This study compared the material-specific tissue response to the synthetic, hydroxyapatite-based bone substitute material NanoBone (NB) with that of the xenogeneic, bovine-based bone substitute material Bio-Oss (BO). The sinus cavities of 14 human patients were augmented with NB and BO in a split-mouth design. Six months after augmentation, bone biopsies were extracted for histological and histomorphometric investigation prior to dental implant insertion. The following were evaluated: the cellular inflammatory pattern, the induction of multinucleated giant cells, vascularization, the relative amounts of newly formed bone, connective tissue, and the remaining bone substitute material. NB granules were well integrated in the peri-implant tissue and were surrounded by newly formed bone tissue. Multinucleated giant cells were visible on the surfaces of the remaining granules. BO granules were integrated into the newly formed bone tissue, which originated from active osteoblasts on their surface. Histomorphometric analysis showed a significantly higher number of multinucleated giant cells and blood vessels in the NB group compared to the BO group. No statistical differences were observed in regard to connective tissue, remaining bone substitute, and newly formed bone. The results of this study highlight the different cellular reactions to synthetic and xenogeneic bone substitute materials. The significantly higher number of multinucleated giant cells within the NB implantation bed seems to have no effect on its biodegradation. Accordingly, the multinucleated giant cells observed within the NB implantation bed have characteristics more similar to those of foreign body giant cells than to those of osteoclasts.

Cryopreserved Off-the-Shelf Allogeneic Adipose-Derived Stromal Cells for Therapy in Patients with Ischemic Heart Disease and Heart Failure-A Safety Study.

PubMed

Kastrup, Jens; Haack-Sørensen, Mandana; Juhl, Morten; Harary Søndergaard, Rebekka; Follin, Bjarke; Drozd Lund, Lisbeth; Mønsted Johansen, Ellen; Ali Qayyum, Abbas; Bruun Mathiasen, Anders; Jørgensen, Erik; Helqvist, Steffen; Jørgen Elberg, Jens; Bruunsgaard, Helle; Ekblond, Annette

2017-11-01

The present first-in-human clinical trial evaluated the safety and feasibility of a newly developed and cryopreserved Cardiology Stem Cell Centre adipose-derived stromal cell (CSCC_ASC) product from healthy donors for intramyocardial injection in ten patients with ischemic heart disease and ischemic heart failure (IHF). Batches of CSCC_ASC were isolated from three healthy donors by liposuction from abdominal adipose tissue. Adipose mesenchymal stromal cells were culture expanded in bioreactors without the use of animal constituents, cryopreserved, and stored in vials in nitrogen dry-storage containers until use. Direct injection of CSCC_ASC into the myocardium did not cause any complications or serious adverse events related to either treatment or cell administration in a 6-month follow-up period. Four out of ten heart failure patients developed donor-specific de novo human leukocyte antigen (HLA) class I antibodies, and two out of ten patients had donor-specific HLA antibodies already at baseline. There were no clinical symptoms or changes in inflammatory parameters in the follow-up period that indicated an ongoing immune response. There was a tendency toward improvement in cardiac function after CSCC_ASC treatment at 6-month follow-up: left ventricular end systolic volume decreased and left ventricular ejection fraction increased. In addition, exercise capacity increased. These changes were independent of the presence or absence of HLA antibodies. It is concluded that the newly developed cryopreserved product CSCC_ASC from healthy donors was a safe and feasible treatment. We observed a tendency toward efficacy in patients with IHF. These findings have to be confirmed in larger placebo controlled clinical trials. Stem Cells Translational Medicine 2017;6:1963-1971. © 2017 The Authors Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

Mandibular distraction osteogenesis with newly designed electromechanical distractor.

PubMed

Aykan, Andac; Ugurlutan, Rifat; Zor, Fatih; Ozturk, Serdar

2014-07-01

The purposes of this study were to design a fully automatic electromechanical distractor for continuous mandibular distraction osteogenesis and to investigate the efficacy of this newly developed distractor on sheep mandible model. Five sheep underwent unilateral mandibular osteotomy, and the mechanical component of electromechanical distractor was fixed on both sides of the osteotomy site using pins. After a 5-day latency period, the electromechanical distractor was activated at a rate of 0.30 mm per 8 hours using an electronic control unit. The bone was lengthened for 20 days without any intervention to the electromechanical distractor. The animals were killed on the sixth week of the consolidation period, and 5 distracted mandibles were examined through macroscopic observation and computed tomography. Distracted bone length was measured through computed tomography on sagittal slices. The device was tolerated by the distraction process without complications in all animals. New callus formation was observed on the distraction gap. Radiologic evaluation showed new callus formation in the distraction gap. New callus length was found to be, in average, 18.28 mm. In this preliminary study, a newly designed electromechanical distractor was successfully used for mandible distraction, which mainly provided a continuous lengthening during activation period spontaneously without any intervention. We think that the clinical application of this electromechanic distractor may provide patient comfort during distraction. Moreover, electromechanical distractor has the potential for high-resolution movement capacity when compared with annual distraction. The promising results from this prototype are encouraging to further investigations for human applications.

Advancement of Miniature Optic Gas Sensor (MOGS) Probe Technology

NASA Technical Reports Server (NTRS)

Chullen, Cinda

2015-01-01

Advancement of Miniature Optic Gas Sensor (MOGS) Probe Technology" project will investigate newly developed optic gas sensors delivered from a Small Business Innovative Research (SBIR) Phase II effort. A ventilation test rig will be designed and fabricated to test the sensors while integrated with a Suited Manikin Test Apparatus (SMTA). Once the sensors are integrated, a series of test points will be completed to verify that the sensors can withstand Advanced Suit Portable Life Support System (PLSS) environments and associated human metabolic profiles for changes in pressure and levels of Oxygen (ppO2), carbon dioxide (ppCO2), and humidity (ppH2O).

The gradual emergence of phonological form in a new language

PubMed Central

Aronoff, Mark; Meir, Irit; Padden, Carol

2011-01-01

The division of linguistic structure into a meaningless (phonological) level and a meaningful level of morphemes and words is considered a basic design feature of human language. Although established sign languages, like spoken languages, have been shown to be characterized by this bifurcation, no information has been available about the way in which such structure arises. We report here on a newly emerging sign language, Al-Sayyid Bedouin Sign Language, which functions as a full language but in which a phonological level of structure has not yet emerged. Early indications of formal regularities provide clues to the way in which phonological structure may develop over time. PMID:22223927

Kinetics and thermodynamics of exonuclease-deficient DNA polymerases

NASA Astrophysics Data System (ADS)

Gaspard, Pierre

2016-04-01

A kinetic theory is developed for exonuclease-deficient DNA polymerases, based on the experimental observation that the rates depend not only on the newly incorporated nucleotide, but also on the previous one, leading to the growth of Markovian DNA sequences from a Bernoullian template. The dependencies on nucleotide concentrations and template sequence are explicitly taken into account. In this framework, the kinetic and thermodynamic properties of DNA replication, in particular, the mean growth velocity, the error probability, and the entropy production are calculated analytically in terms of the rate constants and the concentrations. Theory is compared with numerical simulations for the DNA polymerases of T7 viruses and human mitochondria.

The AIDS epidemic: the spread of a deadly disease in the biotech era.

PubMed

Noë, A; Verhofstede, C; Plum, J

2004-01-01

In the last two decades we have witnessed the progression of a newly introduced infection in humans. It is sobering that despite a world-wide effort and the tremendous progression of technical capabilities and scientific knowledge we are still not able to control the global epidemic of HIV. In 2004 more than 40 million people were infected. Educational approaches to modify risk-taking behavior is still the most critical component of prevention and the most important measure to limit the spread of the infection. Vaccine development, which is still far from promising, is probably the only way to control the disease in the future.

REM sleep selectively prunes and maintains new synapses in development and learning.

PubMed

Li, Wei; Ma, Lei; Yang, Guang; Gan, Wen-Biao

2017-03-01

The functions and underlying mechanisms of rapid eye movement (REM) sleep remain unclear. Here we show that REM sleep prunes newly formed postsynaptic dendritic spines of layer 5 pyramidal neurons in the mouse motor cortex during development and motor learning. This REM sleep-dependent elimination of new spines facilitates subsequent spine formation during development and when a new motor task is learned, indicating a role for REM sleep in pruning to balance the number of new spines formed over time. Moreover, REM sleep also strengthens and maintains newly formed spines, which are critical for neuronal circuit development and behavioral improvement after learning. We further show that dendritic calcium spikes arising during REM sleep are important for pruning and strengthening new spines. Together, these findings indicate that REM sleep has multifaceted functions in brain development, learning and memory consolidation by selectively eliminating and maintaining newly formed synapses via dendritic calcium spike-dependent mechanisms.

Validation of an optimized method for the determination of iodine in human breast milk by inductively coupled plasma mass spectrometry (ICPMS) after tetramethylammonium hydroxide extraction.

PubMed

Huynh, Dao; Zhou, Shao Jia; Gibson, Robert; Palmer, Lyndon; Muhlhausler, Beverly

2015-01-01

In this study a novel method to determine iodine concentrations in human breast milk was developed and validated. The iodine was analyzed by inductively coupled plasma mass spectrometry (ICPMS) following tetramethylammonium hydroxide (TMAH) extraction at 90°C in disposable polypropylene tubes. While similar approaches have been used previously, this method adopted a shorter extraction time (1h vs. 3h) and used antimony (Sb) as the internal standard, which exhibited greater stability in breast milk and milk powder matrices compared to tellurium (Te). Method validation included: defining iodine linearity up to 200μgL(-1); confirming recovery of iodine from NIST 1549 milk powder. A recovery of 94-98% was also achieved for the NIST 1549 milk powder and human breast milk samples spiked with sodium iodide and thyroxine (T4) solutions. The method quantitation limit (MQL) for human breast milk was 1.6μgL(-1). The intra-assay and inter-assay coefficient of variation for the breast milk samples and NIST powder were <1% and <3.5%, respectively. NIST 1549 milk powder, human breast milk samples and calibration standards spiked with the internal standard were all stable for at least 2.5 months after extraction. The results of the validation process confirmed that this newly developed method provides greater accuracy and precision in the assessment of iodine concentrations in human breast milk than previous methods and therefore offers a more reliable approach for assessing iodine concentrations in human breast milk. Copyright © 2014 Elsevier GmbH. All rights reserved.

Development of the Human Factors Skills for Healthcare Instrument: a valid and reliable tool for assessing interprofessional learning across healthcare practice settings.

PubMed

Reedy, Gabriel B; Lavelle, Mary; Simpson, Thomas; Anderson, Janet E

2017-10-01

A central feature of clinical simulation training is human factors skills, providing staff with the social and cognitive skills to cope with demanding clinical situations. Although these skills are critical to safe patient care, assessing their learning is challenging. This study aimed to develop, pilot and evaluate a valid and reliable structured instrument to assess human factors skills, which can be used pre- and post-simulation training, and is relevant across a range of healthcare professions. Through consultation with a multi-professional expert group, we developed and piloted a 39-item survey with 272 healthcare professionals attending training courses across two large simulation centres in London, one specialising in acute care and one in mental health, both serving healthcare professionals working across acute and community settings. Following psychometric evaluation, the final 12-item instrument was evaluated with a second sample of 711 trainees. Exploratory factor analysis revealed a 12-item, one-factor solution with good internal consistency (α=0.92). The instrument had discriminant validity, with newly qualified trainees scoring significantly lower than experienced trainees ( t (98)=4.88, p<0.001) and was sensitive to change following training in acute and mental health settings, across professional groups (p<0.001). Confirmatory factor analysis revealed an adequate model fit (RMSEA=0.066). The Human Factors Skills for Healthcare Instrument provides a reliable and valid method of assessing trainees' human factors skills self-efficacy across acute and mental health settings. This instrument has the potential to improve the assessment and evaluation of human factors skills learning in both uniprofessional and interprofessional clinical simulation training.

76 FR 57957 - Notice of Availability of a Draft Supplemental Environmental Impact Statement for Replacement of...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-19

... a geohazard soil stabilization system, structural upgrade to remaining structures, and other site... effects to the human environment. The No-Action Alternative was analyzed and assumes the newly proposed...

Reinforcing the role of the conventional C-arm--a novel method for simplified distal interlocking.

PubMed

Windolf, Markus; Schroeder, Josh; Fliri, Ladina; Dicht, Benno; Liebergall, Meir; Richards, R Geoff

2012-01-25

The common practice for insertion of distal locking screws of intramedullary nails is a freehand technique under fluoroscopic control. The process is technically demanding, time-consuming and afflicted to considerable radiation exposure of the patient and the surgical personnel. A new concept is introduced utilizing information from within conventional radiographic images to help accurately guide the surgeon to place the interlocking bolt into the interlocking hole. The newly developed technique was compared to conventional freehand in an operating room (OR) like setting on human cadaveric lower legs in terms of operating time and radiation exposure. The proposed concept (guided freehand), generally based on the freehand gold standard, additionally guides the surgeon by means of visible landmarks projected into the C-arm image. A computer program plans the correct drilling trajectory by processing the lens-shaped hole projections of the interlocking holes from a single image. Holes can be drilled by visually aligning the drill to the planned trajectory. Besides a conventional C-arm, no additional tracking or navigation equipment is required.Ten fresh frozen human below-knee specimens were instrumented with an Expert Tibial Nail (Synthes GmbH, Switzerland). The implants were distally locked by performing the newly proposed technique as well as the conventional freehand technique on each specimen. An orthopedic resident surgeon inserted four distal screws per procedure. Operating time, number of images and radiation time were recorded and statistically compared between interlocking techniques using non-parametric tests. A 58% reduction in number of taken images per screw was found for the guided freehand technique (7.4 ± 3.4) (mean ± SD) compared to the freehand technique (17.6 ± 10.3) (p < 0.001). Total radiation time (all 4 screws) was 55% lower for the guided freehand technique compared to conventional freehand (p = 0.001). Operating time per screw (from first shot to screw tightened) was on average 22% reduced by guided freehand (p = 0.018). In an experimental setting, the newly developed guided freehand technique for distal interlocking has proven to markedly reduce radiation exposure when compared to the conventional freehand technique. The method utilizes established clinical workflows and does not require cost intensive add-on devices or extensive training. The underlying principle carries potential to assist implant positioning in numerous other applications within orthopedics and trauma from screw insertions to placement of plates, nails or prostheses.

Utility of the National Death Index in Ascertaining Mortality in Acquired Immunodeficiency Syndrome Surveillance

PubMed Central

Trepka, Mary Jo; Maddox, Lorene M.; Lieb, Spencer; Niyonsenga, Theophile

2011-01-01

To assess the utility of the National Death Index (NDI) in improving the ascertainment of deaths among people diagnosed with acquired immunodeficiency syndrome (AIDS), the authors determined the number and characteristics of additional deaths identified through NDI linkage not ascertained by using standard electronic linkage with Florida Vital Records and the Social Security Administration’s Death Master File. Records of people diagnosed with acquired immunodeficiency syndrome between 1993 and 2007 in Florida were linked to the NDI. The demographic characteristics and reported human immunodeficiency virus (HIV) transmission modes of people whose deaths were identified by using the NDI were compared with those whose deaths were ascertained by standard linkage methods. Of the 15,094 submitted records, 719 had confirmed matches, comprising 2.1% of known deaths (n = 34,504) within the cohort. Hispanics, males, people 40 years of age or older, and injection drug users were overrepresented among deaths ascertained only by the NDI. In-state deaths comprised 59.0% of newly identified deaths, and human immunodeficiency virus was less likely to be a cause of death among newly identified compared with previously identified deaths. The newly identified deaths were not previously ascertained principally because of slight differences in personal identifying information and could have been identified through improved linkages with Florida Vital Records. PMID:21540319

Utility of the National Death Index in ascertaining mortality in acquired immunodeficiency syndrome surveillance.

PubMed

Trepka, Mary Jo; Maddox, Lorene M; Lieb, Spencer; Niyonsenga, Theophile

2011-07-01

To assess the utility of the National Death Index (NDI) in improving the ascertainment of deaths among people diagnosed with acquired immunodeficiency syndrome (AIDS), the authors determined the number and characteristics of additional deaths identified through NDI linkage not ascertained by using standard electronic linkage with Florida Vital Records and the Social Security Administration's Death Master File. Records of people diagnosed with acquired immunodeficiency syndrome between 1993 and 2007 in Florida were linked to the NDI. The demographic characteristics and reported human immunodeficiency virus (HIV) transmission modes of people whose deaths were identified by using the NDI were compared with those whose deaths were ascertained by standard linkage methods. Of the 15,094 submitted records, 719 had confirmed matches, comprising 2.1% of known deaths (n = 34,504) within the cohort. Hispanics, males, people 40 years of age or older, and injection drug users were overrepresented among deaths ascertained only by the NDI. In-state deaths comprised 59.0% of newly identified deaths, and human immunodeficiency virus was less likely to be a cause of death among newly identified compared with previously identified deaths. The newly identified deaths were not previously ascertained principally because of slight differences in personal identifying information and could have been identified through improved linkages with Florida Vital Records.

Human vaginal fluid contains exosomes that have an inhibitory effect on an early step of the HIV-1 life cycle.

PubMed

Smith, Johanna A; Daniel, Rene

2016-11-13

Vaginal transmission is crucial to the spread of HIV-1 around the world. It is not yet clear what type (s) of innate defenses against HIV-1 infection are present in the vagina. Here, we aimed to determine whether human vaginal fluid contains exosomes that may possess anti-HIV-1 activity. The exosomal fraction was isolated from samples of vaginal fluids. The presence of exosomes was confirmed by flow cytometry and western blotting. The newly discovered exosomes were tested for their ability to block early steps of HIV-1 infection in vitro using established cell culture systems and real time PCR-based methods. Vaginal fluid contains exosomes expressing CD9, CD63, and CD81 exosomal markers. The exosomal fraction of the fluid-reduced transmission of HIV-1 vectors by 60%, the efficiency of reverse transcription step by 58.4%, and the efficiency of integration by 47%. Exosomes had no effect on the entry of HIV-1 vectors. Human vaginal fluid exosomes are newly discovered female innate defenses that may protect women against HIV-1 infection.

Labiopexy and labioplasty for labium majus rejuvenation in light of a newly discovered anatomic structure.

PubMed

Ostrzenski, Adam

2014-06-01

Currently, removal of excessive cutis with subdermal adipose tissues is done for labium majus rejuvenation. The objectives of this study were to determine the accurate labium majus anatomy, to develop new labiopexy and labioplasty techniques, to attest to the applicability of these two new operations, and to determine the impact of the operations on self-perceived body image and sensation of nerve endings. A prospective case series study was conducted. Eleven fresh human female cadavers and three living subjects were studied. Living subjects were healthy women and presented with labium majus deformities. The study was conducted in three phases: phase I, the labium majus anatomy of the cadavers was studied; phase II, anatomic findings from phase I were used to develop and standardize new stepwise surgical interventions; and phase III, newly developed operations were implemented on living subjects. Labial sensation tests of nerve endings were performed preoperatively and at 6 months postoperatively. The primary outcome measured the labial anatomy and applicability of the new operations. The secondary outcome measured the self-perceived body image and sensation of nerve endings before and after surgery. A new anatomic feature, the labium majus adipose sac, was discovered and was present in each subject. Labium majus labiopexy and labioplasty were executed without technical difficulties or complications. Postoperatively, the self-perceived body image improved and sensation of nerve endings was intact. The labium majus adipose sac is present in each woman. Intraoperatively, newly developed labium majus labiopexy and/or labioplasty do not create technical problems. Self-perceived body image improves and sensation of the nerve endings is intact after labiopexy or labioplasty. This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors http://www.springer.com/00266.

Gut microbiota: puppeteer of the host juvenile growth.

PubMed

Schwarzer, Martin

2018-05-01

This review focuses on the recent discoveries about the impact of intestinal microbiota on mammalian host juvenile growth. Intestinal microbiota is a powerful modulator of many facets of multicellular host's physiology. Recent results from human field studies and animal research have clearly shown that not only the nutrition, but also the intestinal microbiota impacts host postnatal growth kinetics. Absence of microbiome leads to stunted growth in mammalian gnotobiotic models and changes in the composition of the intestinal microbiota can impact the postnatal growth kinetics both positively and negatively under normal nutritional conditions as well as in undernutrition. Strikingly, specific bacterial strains are able to interact with GH/IGF-1 somatotropic axis activity, thus directly impacting host juvenile development. Intestinal microbiota dictates the pace of host postnatal growth. This newly described role envisages that therapy with specific bacterial strains, together with re-nutritional strategies, might successfully alleviate the long-term sequelae of undernutrition during childhood in humans.

Personalized biochemistry and biophysics.

PubMed

Kroncke, Brett M; Vanoye, Carlos G; Meiler, Jens; George, Alfred L; Sanders, Charles R

2015-04-28

Whole human genome sequencing of individuals is becoming rapid and inexpensive, enabling new strategies for using personal genome information to help diagnose, treat, and even prevent human disorders for which genetic variations are causative or are known to be risk factors. Many of the exploding number of newly discovered genetic variations alter the structure, function, dynamics, stability, and/or interactions of specific proteins and RNA molecules. Accordingly, there are a host of opportunities for biochemists and biophysicists to participate in (1) developing tools to allow accurate and sometimes medically actionable assessment of the potential pathogenicity of individual variations and (2) establishing the mechanistic linkage between pathogenic variations and their physiological consequences, providing a rational basis for treatment or preventive care. In this review, we provide an overview of these opportunities and their associated challenges in light of the current status of genomic science and personalized medicine, the latter often termed precision medicine.

Personalized Biochemistry and Biophysics

PubMed Central

2016-01-01

Whole human genome sequencing of individuals is becoming rapid and inexpensive, enabling new strategies for using personal genome information to help diagnose, treat, and even prevent human disorders for which genetic variations are causative or are known to be risk factors. Many of the exploding number of newly discovered genetic variations alter the structure, function, dynamics, stability, and/or interactions of specific proteins and RNA molecules. Accordingly, there are a host of opportunities for biochemists and biophysicists to participate in (1) developing tools to allow accurate and sometimes medically actionable assessment of the potential pathogenicity of individual variations and (2) establishing the mechanistic linkage between pathogenic variations and their physiological consequences, providing a rational basis for treatment or preventive care. In this review, we provide an overview of these opportunities and their associated challenges in light of the current status of genomic science and personalized medicine, the latter often termed precision medicine. PMID:25856502

Analysis of dose-LET distribution in the human body irradiated by high energy hadrons.

PubMed

Sato, T; Tsuda, S; Sakamoto, Y; Yamaguchi, Y; Niita, K

2003-01-01

For the purposes of radiological protection, it is important to analyse profiles of the particle field inside a human body irradiated by high energy hadrons, since they can produce a variety of secondary particles which play an important role in the energy deposition process, and characterise their radiation qualities. Therefore Monte Carlo calculations were performed to evaluate dose distributions in terms of the linear energy transfer of ionising particles (dose-LET distribution) using a newly developed particle transport code (Particle and Heavy Ion Transport code System, PHITS) for incidences of neutrons, protons and pions with energies from 100 MeV to 200 GeV. Based on these calculations, it was found that more than 80% and 90% of the total deposition energies are attributed to ionisation by particles with LET below 10 keV microm(-1) for the irradiations of neutrons and the charged particles, respectively.

Lentiviral vector-based insertional mutagenesis identifies genes associated with liver cancer

PubMed Central

Ranzani, Marco; Cesana, Daniela; Bartholomae, Cynthia C.; Sanvito, Francesca; Pala, Mauro; Benedicenti, Fabrizio; Gallina, Pierangela; Sergi, Lucia Sergi; Merella, Stefania; Bulfone, Alessandro; Doglioni, Claudio; von Kalle, Christof; Kim, Yoon Jun; Schmidt, Manfred; Tonon, Giovanni; Naldini, Luigi; Montini, Eugenio

2013-01-01

Transposons and γ-retroviruses have been efficiently used as insertional mutagens in different tissues to identify molecular culprits of cancer. However, these systems are characterized by recurring integrations that accumulate in tumor cells, hampering the identification of early cancer-driving events amongst bystander and progression-related events. We developed an insertional mutagenesis platform based on lentiviral vectors (LVV) by which we could efficiently induce hepatocellular carcinoma (HCC) in 3 different mouse models. By virtue of LVV’s replication-deficient nature and broad genome-wide integration pattern, LVV-based insertional mutagenesis allowed identification of 4 new liver cancer genes from a limited number of integrations. We validated the oncogenic potential of all the identified genes in vivo, with different levels of penetrance. Our newly identified cancer genes are likely to play a role in human disease, since they are upregulated and/or amplified/deleted in human HCCs and can predict clinical outcome of patients. PMID:23314173

Comparative Genomics and Host Resistance against Infectious Diseases

PubMed Central

Qureshi, Salman T.; Skamene, Emil

1999-01-01

The large size and complexity of the human genome have limited the identification and functional characterization of components of the innate immune system that play a critical role in front-line defense against invading microorganisms. However, advances in genome analysis (including the development of comprehensive sets of informative genetic markers, improved physical mapping methods, and novel techniques for transcript identification) have reduced the obstacles to discovery of novel host resistance genes. Study of the genomic organization and content of widely divergent vertebrate species has shown a remarkable degree of evolutionary conservation and enables meaningful cross-species comparison and analysis of newly discovered genes. Application of comparative genomics to host resistance will rapidly expand our understanding of human immune defense by facilitating the translation of knowledge acquired through the study of model organisms. We review the rationale and resources for comparative genomic analysis and describe three examples of host resistance genes successfully identified by this approach. PMID:10081670

The Effects of Orbital Spaceflight on Human Osteoblastic Cell Physiology and Gene Expression

NASA Technical Reports Server (NTRS)

Turner, R. T.

1999-01-01

The purpose of the proposed study is to establish whether changes in gravitational loading have a direct effect on osteoblasts to regulate TGF-6 expression. The effects of spaceflight and reloading on TGF-B MRNA and peptide levels will be studied in a newly developed line of immortalized human fetal osteoblasts (HFOB) transfected with an SV-40 temperature dependent mutant to generate proliferating, undifferentiated hFOB cells at 33-34 C and a non-proliferating, differentiated HFOB cells at 37-39'C. Unlike previous cell culture models, HFOB cells have unlimited proliferative capacity yet can be precisely regulated to differentiate into mature cells which express mature osteoblast function. If isolated osteoblasts respond to changes in mechanical loading in a manner similar to their response in animals, the cell system could provide a powerful model to investigate the signal transduction pathway for gravitational loading.

Biomechanical and mathematical analysis of human movement in medical rehabilitation science using time-series data from two video cameras and force-plate sensor

NASA Astrophysics Data System (ADS)

Tsuruoka, Masako; Shibasaki, Ryosuke; Box, Elgene O.; Murai, Shunji; Mori, Eiji; Wada, Takao; Kurita, Masahiro; Iritani, Makoto; Kuroki, Yoshikatsu

1994-08-01

In medical rehabilitation science, quantitative understanding of patient movement in 3-D space is very important. The patient with any joint disorder will experience its influence on other body parts in daily movement. The alignment of joints in movement is able to improve under medical therapy process. In this study, the newly developed system is composed of two non- metri CCD video cameras and a force plate sensor, which are controlled simultaneously by a personal computer. By this system time-series digital data from 3-D image photogrammetry, each foot pressure and its center position, is able to provide efficient information for biomechanical and mathematical analysis of human movement. Each specific and common points are indicated in any patient movement. This study suggests more various, quantitative understanding in medical rehabilitation science.

Phage display creates innovative applications to combat hepatitis B virus

PubMed Central

Tan, Wen Siang; Ho, Kok Lian

2014-01-01

Hepatitis B virus (HBV) has killed countless lives in human history. The invention of HBV vaccines in the 20th century has reduced significantly the rate of the viral infection. However, currently there is no effective treatment for chronic HBV carriers. Newly emerging vaccine escape mutants and drug resistant strains have complicated the viral eradication program. The entire world is now facing a new threat of HBV and human immunodeficiency virus co-infection. Could phage display provide solutions to these life-threatening problems? This article reviews critically and comprehensively the innovative and potential applications of phage display in the development of vaccines, therapeutic agents, diagnostic reagents, as well as gene and drug delivery systems to combat HBV. The application of phage display in epitope mapping of HBV antigens is also discussed in detail. Although this review mainly focuses on HBV, the innovative applications of phage display could also be extended to other infectious diseases. PMID:25206271

Annual banned-substance review: analytical approaches in human sports drug testing.

PubMed

Thevis, Mario; Kuuranne, Tiia; Geyer, Hans; Schänzer, Wilhelm

2017-01-01

There has been an immense amount of visibility of doping issues on the international stage over the past 12 months with the complexity of doping controls reiterated on various occasions. Hence, analytical test methods continuously being updated, expanded, and improved to provide specific, sensitive, and comprehensive test results in line with the World Anti-Doping Agency's (WADA) 2016 Prohibited List represent one of several critical cornerstones of doping controls. This enterprise necessitates expediting the (combined) exploitation of newly generated information on novel and/or superior target analytes for sports drug testing assays, drug elimination profiles, alternative test matrices, and recent advances in instrumental developments. This paper is a continuation of the series of annual banned-substance reviews appraising the literature published between October 2015 and September 2016 concerning human sports drug testing in the context of WADA's 2016 Prohibited List. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Preventive detention of sex offenders: the American experience versus international human rights norms.

PubMed

Janus, Eric S

2013-01-01

Nearly two decades after the birth of American Sexually Violent Predator (SVP) laws and the tolerant review of their legitimacy by American courts, European courts and international bodies are beginning to develop a jurisprudence of their own with regard to preventive detention. Applying international human rights norms, these bodies have been significantly less tolerant of preventive detention, looking not only at their design but also at their implementation. Simultaneously, American courts are showing the beginnings of a second look at SVP laws, inspired and informed not by promises about the future implementation of newly passed SVP laws, but rather by the sorry record of two decades of implementation. This article examines an American SVP scheme as it has been implemented over 20 years, contrasts the international perspective, and offers some speculation about the path of reform for American SVP schemes. Copyright © 2013 John Wiley & Sons, Ltd.

Packaging of Human Chromosome 19-Specific Adeno-Associated Virus (AAV) Integration Sites in AAV Virions during AAV Wild-Type and Recombinant AAV Vector Production

PubMed Central

Hüser, Daniela; Weger, Stefan; Heilbronn, Regine

2003-01-01

Adeno-associated virus type 2 (AAV-2) establishes latency by site-specific integration into a unique locus on human chromosome 19, called AAVS1. During the development of a sensitive real-time PCR assay for site-specific integration, AAV-AAVS1 junctions were reproducibly detected in highly purified AAV wild-type and recombinant AAV vector stocks. A series of controls documented that the junctions were packaged in AAV capsids and were newly generated during a single round of AAV production. Cloned junctions displayed variable AAV sequences fused to AAVS1. These data suggest that packaged junctions represent footprints of AAV integration during productive infection. Apparently, AAV latency established by site-specific integration and the helper virus-dependent, productive AAV cycle are more closely related than previously thought. PMID:12663794

6 CFR 7.26 - Derivative classification.

Code of Federal Regulations, 2011 CFR

2011-01-01

... already classified, and marking the newly developed material consistent with the classification markings... classification decisions and carry forward to any newly created documents the pertinent classification markings. (d) Information classified derivatively from other classified information shall be classified and...

Expression of autophagy-related protein LC3B, p62, and cytoplasmic p53 in human retinoblastoma tissues.

PubMed

Zhang, M; Zhou, Y-F; Gong, J-Y; Gao, C-B; Li, S-L

2016-07-01

Dysfunction of autophagy has been implicated in development and progression of diverse human cancers. However, the exact role and mechanism of autophagy have not been fully understood in human cancers, especially in retinoblastoma (Rb). We determined the autophagy activity in human Rb tissues by assessing the autophagy markers microtubule-associated protein light chain 3B (LC3) and p62 (SQSTM1) in formalin fixed and paraffin embedded human tissue by immunohistochemistry and then associated their expression with patient clinicopathological features. We further explored the correlation between the expression of LC3B and p62 and the expression of cytoplasmic p53, a newly identified autophagy suppressor, in Rb tissues. Our data revealed that the expression of LC3B and p62, was significantly associated with disease progression and tumor invasion of Rb. Furthermore, we also revealed that cytoplasmic expression of p53 was inversely associated with the behavior of tumor invasion. Finally, Spearman correlation analysis demonstrated that cytoplasmic expression of p53 was significantly and inversely correlated to the expression of both LC3B and p62. Autophagy might play an important role in human Rb progression, and LC3B and p62 may be useful predictors of disease progression in patients with Rb.

Peptide Based Radiopharmaceuticals: Specific Construct Approach

DOE Office of Scientific and Technical Information (OSTI.GOV)

Som, P; Rhodes, B A; Sharma, S S

1997-10-21

The objective of this project was to develop receptor based peptides for diagnostic imaging and therapy. A series of peptides related to cell adhesion molecules (CAM) and immune regulation were designed for radiolabeling with 99mTc and evaluated in animal models as potential diagnostic imaging agents for various disease conditions such as thrombus (clot), acute kidney failure, and inflection/inflammation imaging. The peptides for this project were designed by the industrial partner, Palatin Technologies, (formerly Rhomed, Inc.) using various peptide design approaches including a newly developed rational computer assisted drug design (CADD) approach termed MIDAS (Metal ion Induced Distinctive Array of Structures).more » In this approach, the biological function domain and the 99mTc complexing domain are fused together so that structurally these domains are indistinguishable. This approach allows construction of conformationally rigid metallo-peptide molecules (similar to cyclic peptides) that are metabolically stable in-vivo. All the newly designed peptides were screened in various in vitro receptor binding and functional assays to identify a lead compound. The lead compounds were formulated in a one-step 99mTc labeling kit form which were studied by BNL for detailed in-vivo imaging using various animals models of human disease. Two main peptides usingMIDAS approach evolved and were investigated: RGD peptide for acute renal failure and an immunomodulatory peptide derived from tuftsin (RMT-1) for infection/inflammation imaging. Various RGD based metallopeptides were designed, synthesized and assayed for their efficacy in inhibiting ADP-induced human platelet aggregation. Most of these peptides displayed biological activity in the 1-100 µM range. Based on previous work by others, RGD-I and RGD-II were evaluated in animal models of acute renal failure. These earlier studies showed that after acute ischemic injury the renal cortex displays RGD receptor with higher density. The results have indicated good diagnostic potential for their use in this clinical situation, as an imaging agent to diagnose ischemic renal injury and differentiate from other causes. Very promising results were obtained with newly developed tuftsin related metallopeptides. A number of these peptides displayed high potency (nM range) in imaging infection. Antagonists were successfully used to image experimentally induced abscesses in rodents. One of the antagonists, termed 99mTc-RMT-1, was evaluated in rabbits and dogs for its applicability as infection/inflammation imaging agent. Both in dog and rabbit infection/inflammation models 99mTc-RMT-1 could be used for rapid scintigraphic diagnosis. A very high and rapid uptake was observed in both soft tissue and bone infection providing a good target to background contrast. The agent also allowed distinction between bone fracture and osteomyelitis. All these results warrant human clinical trials with 99mTc-RMT-1 which may help replace hazardous ex-vivo WBC labeling procedures that are current clincial modality for imaging infection foci.« less

Direct comparison of (+/-) 3,4-methylenedioxymethamphetamine ("ecstasy") disposition and metabolism in squirrel monkeys and humans.

PubMed

Mueller, Melanie; Kolbrich, Erin A; Peters, Frank T; Maurer, Hans H; McCann, Una D; Huestis, Marilyn A; Ricaurte, George A

2009-06-01

The present study compared the disposition and metabolism of the recreational drug (+/-) 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") in squirrel monkeys and humans because the squirrel monkey has been extensively studied for MDMA neurotoxicity. A newly developed liquid chromatography-mass spectrometric procedure for simultaneous measurement of MDMA, 3,4-dihydroxymethamphetamine, 4-hydroxy-3-methoxymethamphetamine, and 3,4-methylenedioxyamphetamine was employed. In both humans and squirrel monkeys, a within-subject design permitted testing of different doses in the same subjects. Humans and squirrel monkeys were found to metabolize MDMA in similar, but not identical, pathways and proportions. In particular, amounts of 3,4-dihydroxymethamphetamine (after conjugate cleavage) and 3,4-methylenedioxyamphetamine were similar in the 2 species, but formation of 4-hydroxy-3-methoxymethamphetamine was greater in squirrel monkeys than in humans. Both species demonstrated nonlinear MDMA pharmacokinetics at comparable plasma MDMA concentrations (125-150 ng/mL and above). The elimination half-life of MDMA was considerably shorter in squirrel monkeys than in humans (2-3 versus 6-9 hours). In both species, there was substantial individual variability. These results suggest that the squirrel monkey may be a useful model for predicting outcomes of MDMA exposure in humans, although this will also depend on the degree to which MDMA pharmacodynamics in the squirrel monkey parallels that in humans.

'Doing the writing' and 'working in parallel': how 'distal nursing' affects delegation and supervision in the emerging role of the newly qualified nurse.

PubMed

Johnson, Martin; Magnusson, Carin; Allan, Helen; Evans, Karen; Ball, Elaine; Horton, Khim; Curtis, Kathy; Westwood, Sue

2015-02-01

The role of the acute hospital nurse has moved away from the direct delivery of patient care and more towards the management of the delivery of bedside care by healthcare assistants. How newly qualified nurses delegate to and supervise healthcare assistants is important as failures can lead to care being missed, duplicated and/or incorrectly performed. The data described here form part of a wider study which explored how newly qualified nurses recontextualise knowledge into practice, and develop and apply effective delegation and supervision skills. This article analyses team working between newly qualified nurses and healthcare assistants, and nurses' balancing of administrative tasks with bedside care. Ethnographic case studies were undertaken in three hospital sites in England, using a mixed methods approach involving: participant observations; interviews with 33 newly qualified nurses, 10 healthcare assistants and 12 ward managers. Data were analysed using thematic analysis, aided by the qualitative software NVivo. Multiple demands upon the newly qualified nurses' time, particularly the pressures to maintain records, can influence how effectively they delegate to, and supervise, healthcare assistants. While some nurses and healthcare assistants work successfully together, others work 'in parallel' rather than as an efficient team. While some ward cultures and individual working styles promote effective team working, others lead to less efficient collaboration between newly qualified nurses and healthcare assistants. In particular the need for qualified nurses to maintain records can create a gap between them, and between nurses and patients. Newly qualified nurses require more assistance in managing their own time and developing successful working relationships with healthcare assistants. Copyright © 2014 Elsevier Ltd. All rights reserved.

Genetic characterization of human herpesvirus type 1: Full-length genome sequence of strain obtained from an encephalitis case from India.

PubMed

Bondre, Vijay P; Sankararaman, Vasudha; Andhare, Vijaysinh; Tupekar, Manisha; Sapkal, Gajanan N

2016-11-01

Human herpes simplex virus 1 (HSV-1) is the most common cause of sporadic encephalitis in humans that contributes to >10 per cent of the encephalitis cases occurring worldwide. Availability of limited full genome sequences from a small number of isolates resulted in poor understanding of host and viral factors responsible for variable clinical outcome. In this study genetic relationship, extent and source of recombination using full-length genome sequence derived from a newly isolated HSV-1 isolate was studied in comparison with those sampled from patients with varied clinical outcome. Full genome sequence of HSV-1 isolated from cerebrospinal fluid (CSF) of a patient with acute encephalitis syndrome (AES) by inoculation in baby hamster kidney-21 (BHK-21) cells was determined using next-generation sequencing (NGS) technology. Phylogenetic analysis of the newly generated sequence in comparison with 33 additional full-length genomes defined genetic relationship with worldwide distributed strains. The bootscan and similarity plot analysis defined recombination crossovers and similarities between newly isolated Indian HSV-1 with six Asian and a total of 34 worldwide isolated strains. Mapping of 376,332 reads amplified from HSV-1 DNA by NGS generated full-length genome of 151,024 bp from newly isolated Indian HSV-1. Phylogenetic analysis classified worldwide distributed strains into three major evolutionary lineages correlating to their geographic distribution. Lineage 1 containing strains were isolated from America and Europe; lineage 2 contained all the strains from Asian countries along with the North American KOS and RE strains whereas the South African isolates were distributed into two groups under lineage 3. Recombination analysis confirmed events of recombination in Indian HSV-1 genome resulting from mixing of different strains evolved in Asian countries. Our results showed that the full-length genome sequence generated from an Indian HSV-1 isolate shared close genetic relationship with the American KOS and Chinese CR38 strains which belonged to the Asian genetic lineage. Recombination analysis of Indian isolate demonstrated multiple recombination crossover points throughout the genome. This full-length genome sequence amplified from the Indian isolate would be helpful to study HSV evolution, genetic basis of differential pathogenesis, host-virus interactions and viral factors contributing towards differential clinical outcome in human infections.

Genetic characterization of human herpesvirus type 1: Full-length genome sequence of strain obtained from an encephalitis case from India

PubMed Central

Bondre, Vijay P.; Sankararaman, Vasudha; Andhare, Vijaysinh; Tupekar, Manisha; Sapkal, Gajanan N.

2016-01-01

Background & objectives: Human herpes simplex virus 1 (HSV-1) is the most common cause of sporadic encephalitis in humans that contributes to >10 per cent of the encephalitis cases occurring worldwide. Availability of limited full genome sequences from a small number of isolates resulted in poor understanding of host and viral factors responsible for variable clinical outcome. In this study genetic relationship, extent and source of recombination using full-length genome sequence derived from a newly isolated HSV-1 isolate was studied in comparison with those sampled from patients with varied clinical outcome. Methods: Full genome sequence of HSV-1 isolated from cerebrospinal fluid (CSF) of a patient with acute encephalitis syndrome (AES) by inoculation in baby hamster kidney-21 (BHK-21) cells was determined using next-generation sequencing (NGS) technology. Phylogenetic analysis of the newly generated sequence in comparison with 33 additional full-length genomes defined genetic relationship with worldwide distributed strains. The bootscan and similarity plot analysis defined recombination crossovers and similarities between newly isolated Indian HSV-1 with six Asian and a total of 34 worldwide isolated strains. Results: Mapping of 376,332 reads amplified from HSV-1 DNA by NGS generated full-length genome of 151,024 bp from newly isolated Indian HSV-1. Phylogenetic analysis classified worldwide distributed strains into three major evolutionary lineages correlating to their geographic distribution. Lineage 1 containing strains were isolated from America and Europe; lineage 2 contained all the strains from Asian countries along with the North American KOS and RE strains whereas the South African isolates were distributed into two groups under lineage 3. Recombination analysis confirmed events of recombination in Indian HSV-1 genome resulting from mixing of different strains evolved in Asian countries. Interpretation & conclusions: Our results showed that the full-length genome sequence generated from an Indian HSV-1 isolate shared close genetic relationship with the American KOS and Chinese CR38 strains which belonged to the Asian genetic lineage. Recombination analysis of Indian isolate demonstrated multiple recombination crossover points throughout the genome. This full-length genome sequence amplified from the Indian isolate would be helpful to study HSV evolution, genetic basis of differential pathogenesis, host-virus interactions and viral factors contributing towards differential clinical outcome in human infections. PMID:28361829

The Human Exposure Model (HEM): A Tool to Support Rapid ...

EPA Pesticide Factsheets

The US EPA is developing an open and publically available software program called the Human Exposure Model (HEM) to provide near-field exposure information for Life Cycle Impact Assessments (LCIAs). Historically, LCIAs have often omitted impacts from near-field sources of exposure. The use of consumer products often results in near-field exposures (exposures that occur directly from the use of a product) that are larger than environmentally mediated exposures (i.e. far-field sources)1,2. Failure to consider near-field exposures could result in biases in LCIA-based determinations of the relative sustainability of consumer products. HEM is designed to provide this information.Characterizing near-field sources of chemical exposures present a challenge to LCIA practitioners. Unlike far-field sources, where multimedia mass balance models have been used to determine human exposure, near-field sources require product-specific models of human exposure and considerable information on product use and product composition. Such information is difficult and time-consuming to gather and curate. The HEM software will characterize the distribution of doses and product intake fractions2 across populations of product users and bystanders, allowing for differentiation by various demographic characteristics. The tool incorporates a newly developed database of the composition of more than 17,000 products, data on physical and chemical properties for more than 2,000 chemicals, and mo

Surface modified capillary electrophoresis combined with in solution isoelectric focusing and MALDI-TOF/TOF MS: a gel-free multidimensional electrophoresis approach for proteomic profiling--exemplified on human follicular fluid.

PubMed

Hanrieder, Jörg; Zuberovic, Aida; Bergquist, Jonas

2009-04-24

Development of miniaturized analytical tools continues to be of great interest to face the challenges in proteomic analysis of complex biological samples such as human body fluids. In the light of these challenges, special emphasis is put on the speed and simplicity of newly designed technological approaches as well as the need for cost efficiency and low sample consumption. In this study, we present an alternative multidimensional bottom-up approach for proteomic profiling for fast, efficient and sensitive protein analysis in complex biological matrices. The presented setup was based on sample pre-fractionation using microscale in solution isoelectric focusing (IEF) followed by tryptic digestion and subsequent capillary electrophoresis (CE) coupled off-line to matrix assisted laser desorption/ionization time of flight tandem mass spectrometry (MALDI TOF MS/MS). For high performance CE-separation, PolyE-323 modified capillaries were applied to minimize analyte-wall interactions. The potential of the analytical setup was demonstrated on human follicular fluid (hFF) representing a typical complex human body fluid with clinical implication. The obtained results show significant identification of 73 unique proteins (identified at 95% significance level), including mostly acute phase proteins but also protein identities that are well known to be extensively involved in follicular development.

Development of enhanced piezoelectric energy harvester induced by human motion.

PubMed

Minami, Y; Nakamachi, E

2012-01-01

In this study, a high frequency piezoelectric energy harvester converted from the human low vibrated motion energy was newly developed. This hybrid energy harvester consists of the unimorph piezoelectric cantilever and a couple of permanent magnets. One magnet was attached at the end of cantilever, and the counterpart magnet was set at the end of the pendulum. The mechanical energy provided through the human walking motion, which is a typical ubiquitous presence of vibration, is converted to the electric energy via the piezoelectric cantilever vibration system. At first, we studied the energy convert mechanism and the performance of our energy harvester, where the resonance free vibration of unimorph cantilever with one permanent magnet under a rather high frequency was induced by the artificial low frequency vibration. The counterpart magnet attached on the pendulum. Next, we equipped the counterpart permanent magnet pendulum, which was fluctuated under a very low frequency by the human walking, and the piezoelectric cantilever, which had the permanent magnet at the end. The low-to-high frequency convert "hybrid system" can be characterized as an enhanced energy harvest one. We examined and obtained maximum values of voltage and power in this system, as 1.2V and 1.2 µW. Those results show the possibility to apply for the energy harvester in the portable and implantable Bio-MEMS devices.

[Newly Designed Water Treatment Systems for Hospital Effluent].

PubMed

Azuma, Takashi

2018-01-01

　Pharmaceuticals are indispensable to contemporary life. Recently, the emerging problem of pharmaceutical-based pollution of river environments, including drinking water sources and lakes, has begun to receive significant attention worldwide. Because pharmaceuticals are designed to perform specific physiological functions in targeted regions of the human body, there is increasing concern regarding their toxic effects, even at low concentrations, on aquatic ecosystems and human health, via residues in drinking water. Pharmaceuticals are consistently employed in hospitals to treat disease; and Japan, one of the most advanced countries in medical treatment, ranks second worldwide in the quantity of pharmaceuticals employed. Therefore, the development of technologies that minimize or lessen the related environmental risks for clinical effluent is an important task as well as that for sewage treatment plants (STPs). However, there has been limited research on clinical effluent, and much remains to be elucidated. In light of this, we are investigating the occurrence of pharmaceuticals, and the development of water treatment systems for clinical effluent. This review discusses the current research on clinical effluent and the development of advanced water treatment systems targeted at hospital effluent, and explores strategies for future environmental risk assessment and risk management.

E. coli and water quality: Reevaluation of mug tests and development of radical new indole test. Final technical report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chang, G.W.

1992-12-01

The project was undertaken to address the problem of MUG (4-methylumbelliferyl-B-D-glucuronide)-negative E. coli in water testing, and to develop a new, more reliable indole-based test for E. coli. In a study involving 39 healthy human volunteers, it was found that 1/3 of E. coli isolated from fresh human fecal samples tested MUG-negative in lauryl tryptose broth with MUG. It was further discovered: (1) The presence of simple sugars can cause catabolite repression of beta-GUR in a small percentage of E coli. (2) In gene probe studies, almost all E. coli isolates have portions of the uidA (GUR) gene sequence. Basedmore » on these two findings, catabolite repression can only be a partial explanation for the high-rate of GUR-negative E. coli. The authors improved the E. coli confirmatory medium, EC + MUG by removing the lactose, which allows for a stronger MUG test and the inclusion of the more reliable indole test. They called this newly improved medium INDEC, for Indole and EC medium. They later developed Colitag 3, a one-day, single tube indole-based test for E. coli.« less

HMPAS: Human Membrane Protein Analysis System

PubMed Central

2013-01-01

Background Membrane proteins perform essential roles in diverse cellular functions and are regarded as major pharmaceutical targets. The significance of membrane proteins has led to the developing dozens of resources related with membrane proteins. However, most of these resources are built for specific well-known membrane protein groups, making it difficult to find common and specific features of various membrane protein groups. Methods We collected human membrane proteins from the dispersed resources and predicted novel membrane protein candidates by using ortholog information and our membrane protein classifiers. The membrane proteins were classified according to the type of interaction with the membrane, subcellular localization, and molecular function. We also made new feature dataset to characterize the membrane proteins in various aspects including membrane protein topology, domain, biological process, disease, and drug. Moreover, protein structure and ICD-10-CM based integrated disease and drug information was newly included. To analyze the comprehensive information of membrane proteins, we implemented analysis tools to identify novel sequence and functional features of the classified membrane protein groups and to extract features from protein sequences. Results We constructed HMPAS with 28,509 collected known membrane proteins and 8,076 newly predicted candidates. This system provides integrated information of human membrane proteins individually and in groups organized by 45 subcellular locations and 1,401 molecular functions. As a case study, we identified associations between the membrane proteins and diseases and present that membrane proteins are promising targets for diseases related with nervous system and circulatory system. A web-based interface of this system was constructed to facilitate researchers not only to retrieve organized information of individual proteins but also to use the tools to analyze the membrane proteins. Conclusions HMPAS provides comprehensive information about human membrane proteins including specific features of certain membrane protein groups. In this system, user can acquire the information of individual proteins and specified groups focused on their conserved sequence features, involved cellular processes, and diseases. HMPAS may contribute as a valuable resource for the inference of novel cellular mechanisms and pharmaceutical targets associated with the human membrane proteins. HMPAS is freely available at http://fcode.kaist.ac.kr/hmpas. PMID:24564858

A review on nickel-free nitrogen containing austenitic stainless steels for biomedical applications.

PubMed

Talha, Mohd; Behera, C K; Sinha, O P

2013-10-01

The field of biomaterials has become a vital area, as these materials can enhance the quality and longevity of human life. Metallic materials are often used as biomaterials to replace structural components of the human body. Stainless steels, cobalt-chromium alloys, commercially pure titanium and its alloys are typical metallic biomaterials that are being used for implant devices. Stainless steels have been widely used as biomaterials because of their very low cost as compared to other metallic materials, good mechanical and corrosion resistant properties and adequate biocompatibility. However, the adverse effects of nickel ions being released into the human body have promoted the development of "nickel-free nitrogen containing austenitic stainless steels" for medical applications. Nitrogen not only replaces nickel for austenitic structure stability but also much improves steel properties. Here we review the harmful effects associated with nickel and emphatically the advantages of nitrogen in stainless steel, as well as the development of nickel-free nitrogen containing stainless steels for medical applications. By combining the benefits of stable austenitic structure, high strength, better corrosion and wear resistance and superior biocompatibility in comparison to the currently used austenitic stainless steel (e.g. 316L), the newly developed nickel-free high nitrogen austenitic stainless steel is a reliable substitute for the conventionally used medical stainless steels. Copyright © 2013 Elsevier B.V. All rights reserved.

A fluorimetric readout reporting the kinetics of nucleotide-induced human ribonucleotide reductase oligomerization.

PubMed

Fu, Yuan; Lin, Hongyu; Wisitpitthaya, Somsinee; Blessing, William A; Aye, Yimon

2014-11-24

Human ribonucleotide reductase (hRNR) is a target of nucleotide chemotherapeutics in clinical use. The nucleotide-induced oligomeric regulation of hRNR subunit α is increasingly being recognized as an innate and drug-relevant mechanism for enzyme activity modulation. In the presence of negative feedback inhibitor dATP and leukemia drug clofarabine nucleotides, hRNR-α assembles into catalytically inert hexameric complexes, whereas nucleotide effectors that govern substrate specificity typically trigger α-dimerization. Currently, both knowledge of and tools to interrogate the oligomeric assembly pathway of RNR in any species in real time are lacking. We therefore developed a fluorimetric assay that reliably reports on oligomeric state changes of α with high sensitivity. The oligomerization-directed fluorescence quenching of hRNR-α, covalently labeled with two fluorophores, allows for direct readout of hRNR dimeric and hexameric states. We applied the newly developed platform to reveal the timescales of α self-assembly, driven by the feedback regulator dATP. This information is currently unavailable, despite the pharmaceutical relevance of hRNR oligomeric regulation. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Popp, R.A.; Popp, D.M.; Johnson, F.M.

Mice homozygous for a spontaneous mutation, in which the ..beta..-major globin gene is deleted, have clinical symptoms of ..beta..-thalassemia. These mice have a hypocellular, hypochromic, microcytic anemia that becomes more severe with increasing age. The defective red cell morphology, decreased osmotic fragility of erythrocytes and shortened red cell life span found in ..beta..-thalassemic mice are similar to those observed in human ..beta..-thalassemia. Synthesis of ..beta..-globin is depressed but not as much as might be expected because the expression of the..beta..-minor globin gene is enhanced to encode two to three times more globin than in normal mice. Splenomegaly, an enlarged poolmore » of stem cells for erythropoiesis, and iron overloading occur in older mice. The fact that these mice remain moderately healthy makes them a very suitable animal model in which to develop and test alternative techniques of gene therapy that could be successfully applied to the treatment of human thalassemia. Homozygous ..beta..-thalassemic mice have large deposits of iron in their tissues, which might make these mice also useful for in vivo tests of the effectiveness and possible long-term side effects for newly developed iron chelators.« less

The Developmental Process of the Growing Motile Ciliary Tip Region.

PubMed

Reynolds, Matthew J; Phetruen, Tanaporn; Fisher, Rebecca L; Chen, Ke; Pentecost, Brian T; Gomez, George; Ounjai, Puey; Sui, Haixin

2018-05-22

Eukaryotic motile cilia/flagella play vital roles in various physiological processes in mammals and some protists. Defects in cilia formation underlie multiple human disorders, known as ciliopathies. The detailed processes of cilia growth and development are still far from clear despite extensive studies. In this study, we characterized the process of cilium formation (ciliogenesis) by investigating the newly developed motile cilia of deciliated protists using complementary techniques in electron microscopy and image analysis. Our results demonstrated that the distal tip region of motile cilia exhibit progressive morphological changes as cilia develop. This developmental process is time-dependent and continues after growing cilia reach their full lengths. The structural analysis of growing ciliary tips revealed that B-tubules of axonemal microtubule doublets terminate far away from the tip end, which is led by the flagellar tip complex (FTC), demonstrating that the FTC might not directly mediate the fast turnover of intraflagellar transport (IFT).

Cytological Evaluation and REBA HPV-ID HPV Testing of Newly Developed Liquid-Based Cytology, EASYPREP: Comparison with SurePath.

PubMed

Lee, Youn Soo; Gong, Gyungyub; Sohn, Jin Hee; Ryu, Ki Sung; Lee, Jung Hun; Khang, Shin Kwang; Cho, Kyung-Ja; Kim, Yong-Man; Kang, Chang Suk

2013-06-01

The objective of this study was to evaluate a newly-developed EASYPREP liquid-based cytology method in cervicovaginal specimens and compare it with SurePath. Cervicovaginal specimens were prospectively collected from 1,000 patients with EASYPREP and SurePath. The specimens were first collected by brushing for SurePath and second for EASYPREP. The specimens of both methods were diagnosed according to the Bethesda System. Additionally, we performed to REBA HPV-ID genotyping and sequencing analysis for human papillomavirus (HPV) on 249 specimens. EASYPREP and SurePath showed even distribution of cells and were equal in cellularity and staining quality. The diagnostic agreement between the two methods was 96.5%. Based on the standard of SurePath, the sensitivity, specificity, positive predictive value, and negative predictive value of EASYPREP were 90.7%, 99.2%, 94.8%, and 98.5%, respectively. The positivity of REBA HPV-ID was 49.4% and 95.1% in normal and abnormal cytological samples, respectively. The result of REBA HPV-ID had high concordance with sequencing analysis. EASYPREP provided comparable results to SurePath in the diagnosis and staining quality of cytology examinations and in HPV testing with REBA HPV-ID. EASYPREP could be another LBC method choice for the cervicovaginal specimens. Additionally, REBA HPV-ID may be a useful method for HPV genotyping.

Development and application of a universal Hemoplasma screening assay based on the SYBR green PCR principle.

PubMed

Willi, Barbara; Meli, Marina L; Lüthy, Ruedi; Honegger, Hanspeter; Wengi, Nicole; Hoelzle, Ludwig E; Reusch, Claudia E; Lutz, Hans; Hofmann-Lehmann, Regina

2009-12-01

Hemotropic mycoplasmas (hemoplasmas) are the causative agents of infectious anemia in several mammalian species. Their zoonotic potential has recently been substantiated by the identification of a feline hemoplasma isolate in an immunocompromised human patient. Although species-specific diagnostic molecular methods have been developed, their application as screening tools is limited due to the species diversity of hemoplasmas. The goals of this study were to develop a universal hemoplasma screening assay with broad specificity based on the SYBR green PCR principle, to compare the assay with hemoplasma-specific TaqMan PCR, and to analyze potential tick vectors and human blood samples to address the zoonotic potential. The newly developed PCR assay based on the 16S rRNA gene amplified feline, canine, bovine, porcine, camelid, and murine hemoplasmas, as well as Mycoplasma penetrans and Mycoplasma pneumoniae. The lower detection limit for feline and canine hemoplasmas was 1 to 10 copies/PCR. The assay exhibited 98.2% diagnostic sensitivity and 92.1% diagnostic specificity for feline hemoplasmas. All 1,950 Ixodes ticks were PCR negative, suggesting that Ixodes ticks are not relevant vectors for the above-mentioned hemoplasma species in Switzerland. None of the 414 blood samples derived from anemic or immunocompromised human patients revealed a clear positive result. The SYBR green PCR assay described here is a suitable tool to screen for known and so-far-undiscovered hemoplasma species. Positive results should be confirmed by specific TaqMan PCR or sequencing.

Quantitative analysis of Hedgehog gradient formation using an inducible expression system

PubMed Central

Su, Vivian F; Jones, Kelly A; Brodsky, Michael; The, Inge

2007-01-01

Background The Hedgehog (Hh) family of secreted growth factors are morphogens that act in development to direct growth and patterning. Mutations in human Hh and other Hh pathway components have been linked to human diseases. Analysis of Hh distribution during development indicates that cholesterol modification and receptor mediated endocytosis affect the range of Hh signaling and the cellular localization of Hh. Results We have used an inducible, cell type-specific expression system to characterize the three-dimensional distribution of newly synthesized, GFP-tagged Hh in the developing Drosophila wing. Following induction of Hh-GFP expression in posterior producing cells, punctate structures containing Hh-GFP were observed in the anterior target cells. The distance of these particles from the expressing cells was quantified to determine the shape of the Hh gradient at different time points following induction. The majority of cholesterol-modified Hh-GFP was found associated with cells near the anterior/posterior (A/P) boundary, which express high levels of Hh target genes. Without cholesterol, the Hh gradient was flatter, with a lower percentage of particles near the source and a greater maximum distance. Inhibition of Dynamin-dependent endocytosis blocked formation of intracellular Hh particles, but did not prevent movement of newly synthesized Hh to the apical or basolateral surfaces of target cells. In the absence of both cholesterol and endocytosis, Hh particles accumulated in the extracellular space. Staining for the Hh receptor Ptc revealed four categories of Hh particles: cytoplasmic with and without Ptc, and cell surface with and without Ptc. Interestingly, mainly cholesterol-modified Hh is detected in the cytoplasmic particles lacking Ptc. Conclusion We have developed a system to quantitatively analyze Hh distribution during gradient formation. We directly demonstrate that inhibition of Dynamin-dependent endocytosis is not required for movement of Hh across target cells, indicating that transcytosis is not required for Hh gradient formation. The localization of Hh in these cells suggests that Hh normally moves across both apical and basolateral regions of the target cells. We also conclude that cholesterol modification is required for formation of a specific subset of Hh particles that are both cytoplasmic and not associated with the receptor Ptc. PMID:17484784

Quantitative analysis of Hedgehog gradient formation using an inducible expression system.

PubMed

Su, Vivian F; Jones, Kelly A; Brodsky, Michael; The, Inge

2007-05-07

The Hedgehog (Hh) family of secreted growth factors are morphogens that act in development to direct growth and patterning. Mutations in human Hh and other Hh pathway components have been linked to human diseases. Analysis of Hh distribution during development indicates that cholesterol modification and receptor mediated endocytosis affect the range of Hh signaling and the cellular localization of Hh. We have used an inducible, cell type-specific expression system to characterize the three-dimensional distribution of newly synthesized, GFP-tagged Hh in the developing Drosophila wing. Following induction of Hh-GFP expression in posterior producing cells, punctate structures containing Hh-GFP were observed in the anterior target cells. The distance of these particles from the expressing cells was quantified to determine the shape of the Hh gradient at different time points following induction. The majority of cholesterol-modified Hh-GFP was found associated with cells near the anterior/posterior (A/P) boundary, which express high levels of Hh target genes. Without cholesterol, the Hh gradient was flatter, with a lower percentage of particles near the source and a greater maximum distance. Inhibition of Dynamin-dependent endocytosis blocked formation of intracellular Hh particles, but did not prevent movement of newly synthesized Hh to the apical or basolateral surfaces of target cells. In the absence of both cholesterol and endocytosis, Hh particles accumulated in the extracellular space. Staining for the Hh receptor Ptc revealed four categories of Hh particles: cytoplasmic with and without Ptc, and cell surface with and without Ptc. Interestingly, mainly cholesterol-modified Hh is detected in the cytoplasmic particles lacking Ptc. We have developed a system to quantitatively analyze Hh distribution during gradient formation. We directly demonstrate that inhibition of Dynamin-dependent endocytosis is not required for movement of Hh across target cells, indicating that transcytosis is not required for Hh gradient formation. The localization of Hh in these cells suggests that Hh normally moves across both apical and basolateral regions of the target cells. We also conclude that cholesterol modification is required for formation of a specific subset of Hh particles that are both cytoplasmic and not associated with the receptor Ptc.

Composition of Gut Microbiota Influences Resistance of Newly Hatched Chickens to Salmonella Enteritidis Infection

PubMed Central

Varmuzova, Karolina; Kubasova, Tereza; Davidova-Gerzova, Lenka; Sisak, Frantisek; Havlickova, Hana; Sebkova, Alena; Faldynova, Marcela; Rychlik, Ivan

2016-01-01

Since poultry is a very common source of non-typhoid Salmonella for humans, different interventions aimed at decreasing the prevalence of Salmonella in chickens are understood as an effective measure for decreasing the incidence of human salmonellosis. One such intervention is the use of probiotic or competitive exclusion products. In this study we tested whether microbiota from donor hens of different age will equally protect chickens against Salmonella Enteritidis infection. Newly hatched chickens were therefore orally inoculated with cecal extracts from 1-, 3-, 16-, 28-, and 42-week-old donors and 7 days later, the chickens were infected with S. Enteritidis. The experiment was terminated 4 days later. In the second experiment, groups of newly hatched chickens were inoculated with cecal extracts of 35-week-old hens either on day 1 of life followed by S. Enteritidis infection on day 2 or were infected with S. Enteritidis infection on day 1 followed by therapeutic administration of the cecal extract on day 2 or were inoculated on day 1 of life with a mixture of the cecal extract and S. Enteritidis. This experiment was terminated when the chickens were 5 days old. Both Salmonella culture and chicken gene expression confirmed that inoculation of newly hatched chickens with microbiota from 3-week-old or older chickens protected them against S. Enteritidis challenge. On the other hand, microbiota from 1-week-old donors failed to protect chickens against S. Enteritidis challenge. Microbiota from 35-week-old hens protected chickens even 24 h after administration. However, simultaneous or therapeutic microbiota administration failed to protect chickens against S. Enteritidis infection. Gut microbiota can be used as a preventive measure against S. Enteritidis infection but its composition and early administration is critical for its efficacy. PMID:27379083

Infectious disease emergence and global change: thinking systemically in a shrinking world

PubMed Central

2012-01-01

Background Concern intensifying that emerging infectious diseases and global environmental changes that could generate major future human pandemics. Method A focused literature review was undertaken, partly informed by a forthcoming report on environment, agriculture and infectious diseases of poverty, facilitated by the Special Programme for Tropical Diseases. Results More than ten categories of infectious disease emergence exist, but none formally analyse past, current or future burden of disease. Other evidence suggests that the dominant public health concern focuses on two informal groupings. Most important is the perceived threat of newly recognised infections, especially viruses that arise or are newly discovered in developing countries that originate in species exotic to developed countries, such as non-human primates, bats and rodents. These pathogens may be transmitted by insects or bats, or via direct human contact with bushmeat. The second group is new strains of influenza arising from intensively farmed chickens or pigs, or emerging from Asian “wet markets” where several bird species have close contact. Both forms appear justified because of two great pandemics: HIV/AIDS (which appears to have originated from bushmeat hunting in Africa before emerging globally) and Spanish influenza, which killed up to 2.5% of the human population around the end of World War I. Insufficiently appreciated is the contribution of the milieu which appeared to facilitate the high disease burden in these pandemics. Additionally, excess anxiety over emerging infectious diseases diverts attention from issues of greater public health importance, especially: (i) existing (including neglected) infectious diseases and (ii) the changing milieu that is eroding the determinants of immunity and public health, caused by adverse global environmental changes, including climate change and other components of stressed life and civilisation-supporting systems. Conclusions The focus on novel pathogens and minor forms of anti-microbial resistance in emerging disease literature is unjustified by their burden of disease, actual and potential, and diverts attention from far more important health problems and determinants. There is insufficient understanding of systemic factors that promote pandemics. Adverse global change could generate circumstances conducive to future pandemics with a high burden of disease, arising via anti-microbial and insecticidal resistance, under-nutrition, conflict, and public health breakdown. PMID:23849217

Plasmodium knowlesi from archival blood films: Further evidence that human infections are widely distributed and not newly emergent in Malaysian Borneo

PubMed Central

Lee, Kim-Sung; Cox-Singh, Janet; Brooke, George; Matusop, Asmad; Singh, Balbir

2009-01-01

Human infections with Plasmodium knowlesi have been misdiagnosed by microscopy as Plasmodium malariae due to their morphological similarities. Although microscopy-identified P. malariae cases have been reported in the state of Sarawak (Malaysian Borno) as early as 1952, recent epidemiological studies suggest the absence of indigenous P. malariae infections. The present study aimed to determine the past incidence and distribution of P. knowlesi infections in the state of Sarawak based on archival blood films from patients diagnosed by microscopy as having P. malariae infections. Nested PCR assays were used to identify Plasmodium species in DNA extracted from 47 thick blood films collected in 1996 from patients in seven different divisions throughout the state of Sarawak. Plasmodium knowlesi DNA was detected in 35 (97.2%) of 36 blood films that were positive for Plasmodium DNA, with patients originating from all seven divisions. Only one sample was positive for P. malariae DNA. This study provides further evidence of the widespread distribution of human infections with P. knowlesi in Sarawak and its past occurrence. Taken together with data from previous studies, our findings suggest that P. knowlesi malaria is not a newly emergent disease in humans. PMID:19358848

A new liquid chromatography-mass spectrometry-based method to quantitate exogenous recombinant transferrin in cerebrospinal fluid: a potential approach for pharmacokinetic studies of transferrin-based therapeutics in the central nervous systems.

PubMed

Wang, Shunhai; Bobst, Cedric E; Kaltashov, Igor A

2015-01-01

Transferrin (Tf) is an 80 kDa iron-binding protein that is viewed as a promising drug carrier to target the central nervous system as a result of its ability to penetrate the blood-brain barrier. Among the many challenges during the development of Tf-based therapeutics, the sensitive and accurate quantitation of the administered Tf in cerebrospinal fluid (CSF) remains particularly difficult because of the presence of abundant endogenous Tf. Herein, we describe the development of a new liquid chromatography-mass spectrometry-based method for the sensitive and accurate quantitation of exogenous recombinant human Tf in rat CSF. By taking advantage of a His-tag present in recombinant Tf and applying Ni affinity purification, the exogenous human serum Tf can be greatly enriched from rat CSF, despite the presence of the abundant endogenous protein. Additionally, we applied a newly developed (18)O-labeling technique that can generate internal standards at the protein level, which greatly improved the accuracy and robustness of quantitation. The developed method was investigated for linearity, accuracy, precision, and lower limit of quantitation, all of which met the commonly accepted criteria for bioanalytical method validation.

Probiotics, antibiotics and the immune responses to vaccines.

PubMed

Praharaj, Ira; John, Sushil M; Bandyopadhyay, Rini; Kang, Gagandeep

2015-06-19

Orally delivered vaccines have been shown to perform poorly in developing countries. There are marked differences in the structure and the luminal environment of the gut in developing countries resulting in changes in immune and barrier function. Recent studies using newly developed technology and analytic methods have made it increasingly clear that the intestinal microbiota activate a multitude of pathways that control innate and adaptive immunity in the gut. Several hypotheses have been proposed for the underperformance of oral vaccines in developing countries, and modulation of the intestinal microbiota is now being tested in human clinical trials. Supplementation with specific strains of probiotics has been shown to have modulatory effects on intestinal and systemic immune responses in animal models and forms the basis for human studies with vaccines. However, most studies published so far that have evaluated the immune response to vaccines in children and adults have been small and results have varied by age, antigen, type of antibody response and probiotic strain. Use of anthelminthic drugs in children has been shown to possibly increase immunogenicity following oral cholera vaccination, lending further support to the rationale for modulation of the immune response to oral vaccination through the intestinal microbiome. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

A Computer Clone of Human Expert for Mobility Management Scheme (E-MMS): Step toward Green Transportation

NASA Astrophysics Data System (ADS)

Resdiansyah; O. K Rahmat, R. A.; Ismail, A.

2018-03-01

Green transportation refers to a sustainable transport that gives the least impact in terms of social and environmental but at the same time is able to supply energy sources globally that includes non-motorized transport strategies deployment to promote healthy lifestyles, also known as Mobility Management Scheme (MMS). As construction of road infrastructure cannot help solve the problem of congestion, past research has shown that MMS is an effective measure to mitigate congestion and to achieve green transportation. MMS consists of different strategies and policies that subdivided into categories according to how they are able to influence travel behaviour. Appropriate selection of mobility strategies will ensure its effectiveness in mitigating congestion problems. Nevertheless, determining appropriate strategies requires human expert and depends on a number of success factors. This research has successfully developed a computer clone system based on human expert, called E-MMS. The process of knowledge acquisition for MMS strategies and the next following process to selection of strategy has been encode in a knowledge-based system using a shell expert system. The newly developed computer cloning system was successfully verified, validated and evaluated (VV&E) by comparing the result output with the real transportation expert recommendation in which the findings suggested Introduction

Focused glycomic analysis of the N-linked glycan biosynthetic pathway in ovarian cancer

PubMed Central

Abbott, Karen L.; Nairn, Alison V.; Hall, Erica M.; Horton, Marc B.; McDonald, John F.; Moremen, Kelley W.; Dinulescu, Daniela M.; Pierce, Michael

2014-01-01

Epithelial ovarian cancer is the deadliest female reproductive tract malignancy in Western countries. Less than 25% of cases are diagnosed when the cancer is confined, however, pointing to the critical need for early diagnostics for ovarian cancer. Identifying the changes that occur in the glycome of ovarian cancer cells may provide an avenue to develop a new generation of potential biomarkers for early detection of this disease. We performed a glycotranscriptomic analysis of endometrioid ovarian carcinoma using human tissue, as well as a newly developed mouse model that mimics this disease. Our results show that the N-linked glycans expressed in both non-diseased mouse and human ovarian tissues are similar; moreover, malignant changes in the expression of N-linked glycans in both mouse and human endometrioid ovarian carcinoma are qualitatively similar. Lectin reactivity was used as a means for rapid validation of glycan structural changes in the carcinomas that were predicted by the glycotranscriptome analysis. Among several changes in glycan expression noted, the increase of bisected N-linked glycans and the transcripts of the enzyme responsible for its biosynthesis, GnT-III, was the most significant. This study provides evidence that glycotranscriptome analysis can be an important tool in identifying potential cancer biomarkers. PMID:18690643

REM sleep selectively prunes and maintains new synapses in development and learning

PubMed Central

Li, Wei; Ma, Lei; Yang, Guang; Gan, Wenbiao

2017-01-01

The functions and underlying mechanisms of rapid eye movement (REM) sleep remain unclear. Here we show that REM sleep prunes newly-formed postsynaptic dendritic spines of layer 5 pyramidal neurons in the mouse motor cortex during development and motor learning. This REM sleep-dependent elimination of new spines facilitates subsequent spine formation in development and when a new motor task is learned, indicating a role of REM sleep in pruning to balance the number of new spines formed over time. In addition, REM sleep also strengthens and maintains some newly-formed spines that are critical for neuronal circuit development and behavioral improvement after learning. We further show that dendritic calcium spikes arising during REM sleep are important for pruning and strengthening of new spines. Together, these findings indicate that REM sleep has multifaceted functions in brain development, learning, and memory consolidation by selectively eliminating and maintaining newly-formed synapses via dendritic calcium spike-dependent mechanisms. PMID:28092659

Riems influenza a typing array (RITA): An RT-qPCR-based low density array for subtyping avian and mammalian influenza a viruses.

PubMed

Hoffmann, Bernd; Hoffmann, Donata; Henritzi, Dinah; Beer, Martin; Harder, Timm C

2016-06-03

Rapid and sensitive diagnostic approaches are of the utmost importance for the detection of humans and animals infected by specific influenza virus subtype(s). Cascade-like diagnostics starting with the use of pan-influenza assays and subsequent subtyping devices are normally used. Here, we demonstrated a novel low density array combining 32 TaqMan(®) real-time RT-PCR systems in parallel for the specific detection of the haemagglutinin (HA) and neuraminidase (NA) subtypes of avian and porcine hosts. The sensitivity of the newly developed system was compared with that of the pan-influenza assay, and the specificity of all RT-qPCRs was examined using a broad panel of 404 different influenza A virus isolates representing 45 different subtypes. Furthermore, we analysed the performance of the RT-qPCR assays with diagnostic samples obtained from wild birds and swine. Due to the open format of the array, adaptations to detect newly emerging influenza A virus strains can easily be integrated. The RITA array represents a competitive, fast and sensitive subtyping tool that requires neither new machinery nor additional training of staff in a lab where RT-qPCR is already established.

Identification of a novel human deoxynivalenol metabolite enhancing proliferation of intestinal and urinary bladder cells

PubMed Central

Warth, Benedikt; Del Favero, Giorgia; Wiesenberger, Gerlinde; Puntscher, Hannes; Woelflingseder, Lydia; Fruhmann, Philipp; Sarkanj, Bojan; Krska, Rudolf; Schuhmacher, Rainer; Adam, Gerhard; Marko, Doris

2016-01-01

The mycotoxin deoxynivalenol (DON) is an abundant contaminant of cereal based food and a severe issue for global food safety. We report the discovery of DON-3-sulfate as a novel human metabolite and potential new biomarker of DON exposure. The conjugate was detectable in 70% of urine samples obtained from pregnant women in Croatia. For the measurement of urinary metabolites, a highly sensitive and selective LC-MS/MS method was developed and validated. The method was also used to investigate samples from a duplicate diet survey for studying the toxicokinetics of DON-3-sulfate. To get a preliminary insight into the biological relevance of the newly discovered DON-sulfates, in vitroexperiments were performed. In contrast to DON, sulfate conjugates lacked potency to suppress protein translation. However, surprisingly we found that DON-sulfates enhanced proliferation of human HT-29 colon carcinoma cells, primary human colon epithelial cells (HCEC-1CT) and, to some extent, also T24 bladder cancer cells. A proliferative stimulus, especially in tumorigenic cells raises concern on the potential impact of DON-sulfates on consumer health. Thus, a further characterization of their toxicological relevance should be of high priority. PMID:27659167

Identification of a novel human deoxynivalenol metabolite enhancing proliferation of intestinal and urinary bladder cells

NASA Astrophysics Data System (ADS)

Warth, Benedikt; Del Favero, Giorgia; Wiesenberger, Gerlinde; Puntscher, Hannes; Woelflingseder, Lydia; Fruhmann, Philipp; Sarkanj, Bojan; Krska, Rudolf; Schuhmacher, Rainer; Adam, Gerhard; Marko, Doris

2016-09-01

The mycotoxin deoxynivalenol (DON) is an abundant contaminant of cereal based food and a severe issue for global food safety. We report the discovery of DON-3-sulfate as a novel human metabolite and potential new biomarker of DON exposure. The conjugate was detectable in 70% of urine samples obtained from pregnant women in Croatia. For the measurement of urinary metabolites, a highly sensitive and selective LC-MS/MS method was developed and validated. The method was also used to investigate samples from a duplicate diet survey for studying the toxicokinetics of DON-3-sulfate. To get a preliminary insight into the biological relevance of the newly discovered DON-sulfates, in vitroexperiments were performed. In contrast to DON, sulfate conjugates lacked potency to suppress protein translation. However, surprisingly we found that DON-sulfates enhanced proliferation of human HT-29 colon carcinoma cells, primary human colon epithelial cells (HCEC-1CT) and, to some extent, also T24 bladder cancer cells. A proliferative stimulus, especially in tumorigenic cells raises concern on the potential impact of DON-sulfates on consumer health. Thus, a further characterization of their toxicological relevance should be of high priority.

Application of a novel large-volume injection method using a stomach-shaped inlet liner in capillary gas chromatographic trace analysis of dioxins in human milk and plasma.

PubMed

Saito, Koichi; Ohmura, Atsuko; Takekuma, Mikiko; Sasano, Ryoichi; Matsuki, Yasuhiko; Nakazawa, Hiroyuki

2007-06-01

A newly developed large-volume injection (LVI) technique that employs a unique stomach-shaped inlet liner (SSIL) inside of a programmable temperature vaporizer was used for the determination of trace amounts of dioxins in human milk and plasma. The initial temperature and the initial dwelling time of the inlet and the kind of solvent used were found to be critical in determining the analytical sensitivity of dioxins due to the loss of these relatively volatile compounds during solvent vaporization. Human milk and plasma were purified and fractionated by pre-packed multi-layered silica-gel chromatography and activated carbon silica-gel column chromatography. A 20-microL aliquot of the fraction collected from the chromatography with toluene was directly applied to the LVI system in high-resolution gas chromatography/high-resolution mass spectrometry. Excellent correlation (r > 0.97) between the values obtained by the LVI method using the SSIL device and those by the conventional regular-volume splitless injection method was obtained for PCDDs, PCDFs and non-ortho PCBs in human milk and plasma samples.

Man-equivalent telepresence through four fingered human-like hand system

NASA Technical Reports Server (NTRS)

Jau, Bruno M.

1992-01-01

The author describes a newly developed mechanical hand system. The robot hand is in human-like configuration with a thumb and three fingers, a palm, a wrist, and the forearm in which the hand and wrist actuators are located. Each finger and the wrist has its own active electromechanical compliance system, allowing the joint drive trains to be stiffened or loosened. This mechanism imitates the human muscle dual function of positioner and stiffness controller. This is essential for soft grappling operations. The hand-wrist assembly has 16 finger joints, three wrist joints, and five compliance mechanisms for a total of 24 degrees of freedom. The strength of the hand is roughly half that of the human hand and its size is comparable to a male hand. The hand is controlled through an exoskeleton glove controller that the operator wears. The glove provides the man-machine interface in telemanipulation control mode: it senses the operator's inputs to guide the mechanical hand in hybrid position and force control. The hand system is intended for dexterous manipulations in structured environments. Typical applications will include work in hostile environment such as space operations and nuclear power plants.

X-ray investigation of cross-breed silk in cocoon, yarn and fabric forms

DOE Office of Scientific and Technical Information (OSTI.GOV)

Radhalakshmi, Y. C.; Kariappa,; Siddaraju, G. N.

2012-06-05

Recently Central Sericulture Research and Training Institute, Mysore developed many improved cross breeds and bivoltine hybrids. Newly developed cross breeds recorded fibre characteristics which are significantly superior over existing control hybrids. This aspect has been investigated using X-ray diffraction technique. We have employed line profile analysis to compute microstructural parameters. These parameters are compared with physical parameters of newly developed cross breed silk fibers for a better understanding of structure-property relation in these samples.

The spectroscopic characterization of newly developed emissive materials and the effects of environment on their photophysical properties

NASA Astrophysics Data System (ADS)

McNamara, Louis Edward, III

The development of new materials capable of efficient charge transfer and energy storage has become increasingly important in many areas of modern chemical research. This is especially true for the development of emissive optoelectronic devices and in the field of solar to electric energy conversion. The characterization of the photophysical properties of new molecular systems for these applications has become critical in the design and development of these materials. Many molecular building blocks have been developed and understanding the properties of these molecules at a fundamental level is essential for their successful implementation and future engineering. This dissertation focuses on the characterization of some of these newly-developed molecular systems. The spectroscopic studies focus on the characterization of newly-developed molecules based on perylene and indolizine derivatives for solar to electric energy conversion, thienopyrazine derivatives for near infrared (NIR) emissive applications, an SCS pincer complex for blue emissive materials and a fluorescent probe for medical applications. The effects of noncovalent interactions are also investigated on these systems and a benchmark biological molecule trimethylamine N-oxide (TMAO).

Newly Developed Techniques on Polycondensation, Ring-Opening Polymerization and Polymer Modification: Focus on Poly(Lactic Acid)

PubMed Central

Hu, Yunzi; Daoud, Walid A.; Cheuk, Kevin Ka Leung; Lin, Carol Sze Ki

2016-01-01

Polycondensation and ring-opening polymerization are two important polymer synthesis methods. Poly(lactic acid), the most typical biodegradable polymer, has been researched extensively from 1900s. It is of significant importance to have an up-to-date review on the recent improvement in techniques for biodegradable polymers. This review takes poly(lactic acid) as the example to present newly developed polymer synthesis techniques on polycondensation and ring-opening polymerization reported in the recent decade (2005–2015) on the basis of industrial technique modifications and advanced laboratory research. Different polymerization methods, including various solvents, heating programs, reaction apparatus and catalyst systems, are summarized and compared with the current industrial production situation. Newly developed modification techniques for polymer properties improvement are also discussed based on the case of poly(lactic acid). PMID:28773260

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kirk, Bernadette Lugue; Eipeldauer, Mary D; Whitaker, J Michael

In 2007, the Department of Energy's National Nuclear Security Administration (DOE/NNSA) Office of Nonproliferation and International Security (NA-24) completed a comprehensive review of the current and potential future challenges facing the international safeguards system. The review examined trends and events impacting the mission of international safeguards and the implications of expanding and evolving mission requirements on the legal authorities and institutions that serve as the foundation of the international safeguards system, as well as the technological, financial, and human resources required for effective safeguards implementation. The review's findings and recommendations were summarized in the report, 'International Safeguards: Challenges and Opportunitiesmore » for the 21st Century (October 2007)'. One of the report's key recommendations was for DOE/NNSA to launch a major new program to revitalize the international safeguards technology and human resource base. In 2007, at the International Atomic Energy Agency's General Conference, then Secretary of Energy Samuel W. Bodman announced the newly created Next Generation Safeguards Initiative (NGSI). NGSI consists of five program elements: (1) Policy development and outreach; (2) Concepts and approaches; (3) Technology and analytical methodologies; (4) Human resource development; and (5) Infrastructure development. The ensuing report addresses the 'Human Resource Development (HRD)' component of NGSI. The goal of the HRD as defined in the NNSA Program Plan (November 2008) is 'to revitalize and expand the international safeguards human capital base by attracting and training a new generation of talent.' One of the major objectives listed in the HRD goal includes education and training, outreach to universities, professional societies, postdoctoral appointments, and summer internships at national laboratories. ORNL is a participant in the NGSI program, together with several DOE laboratories such as Pacific Northwest National Laboratory (PNNL), Lawrence Livermore National Laboratory (LLNL), Brookhaven National Laboratory (BNL), and Los Alamos National Laboratory (LANL). In particular, ORNL's participation encompasses student internships, postdoctoral appointments, collaboration with universities in safeguards curriculum development, workshops, and outreach to professional societies through career fairs.« less

Electronic hybridization detection in microarray format and DNA genotyping

NASA Astrophysics Data System (ADS)

Blin, Antoine; Cissé, Ismaïl; Bockelmann, Ulrich

2014-02-01

We describe an approach to substituting a fluorescence microarray with a surface made of an arrangement of electrolyte-gated field effect transistors. This was achieved using a dedicated blocking of non-specific interactions and comparing threshold voltage shifts of transistors exhibiting probe molecules of different base sequence. We apply the approach to detection of the 35delG mutation, which is related to non-syndromic deafness and is one of the most frequent mutations in humans. The process involves barcode sequences that are generated by Tas-PCR, a newly developed replication reaction using polymerase blocking. The barcodes are recognized by hybridization to surface attached probes and are directly detected by the semiconductor device.

Aggregatibacter actinomycetemcomitans Leukotoxin

PubMed Central

Kachlany, S.C.

2010-01-01

Aggregatibacter actinomycetemcomitans is a Gram-negative bacterium that colonizes the human oral cavity and is the causative agent for localized aggressive periodontitis (LAP), an aggressive form of periodontal disease that occurs in adolescents. A. actinomycetemcomitans secretes a protein toxin, leukotoxin (LtxA), which helps the bacterium evade the host immune response during infection. LtxA is a membrane-active toxin that specifically targets white blood cells (WBCs). In this review, we discuss recent developments in this field, including the identification and characterization of genes and proteins involved in secretion, regulation of LtxA, biosynthesis, newly described activities of LtxA, and how LtxA may be used as a therapy for the treatment of diseases. PMID:20200418

Building brains for bodies

NASA Technical Reports Server (NTRS)

Brooks, Rodney Allen; Stein, Lynn Andrea

1994-01-01

We describe a project to capitalize on newly available levels of computational resources in order to understand human cognition. We will build an integrated physical system including vision, sound input and output, and dextrous manipulation, all controlled by a continuously operating large scale parallel MIMD computer. The resulting system will learn to 'think' by building on its bodily experiences to accomplish progressively more abstract tasks. Past experience suggests that in attempting to build such an integrated system we will have to fundamentally change the way artificial intelligence, cognitive science, linguistics, and philosophy think about the organization of intelligence. We expect to be able to better reconcile the theories that will be developed with current work in neuroscience.

Electronic hybridization detection in microarray format and DNA genotyping

PubMed Central

Blin, Antoine; Cissé, Ismaïl; Bockelmann, Ulrich

2014-01-01

We describe an approach to substituting a fluorescence microarray with a surface made of an arrangement of electrolyte-gated field effect transistors. This was achieved using a dedicated blocking of non-specific interactions and comparing threshold voltage shifts of transistors exhibiting probe molecules of different base sequence. We apply the approach to detection of the 35delG mutation, which is related to non-syndromic deafness and is one of the most frequent mutations in humans. The process involves barcode sequences that are generated by Tas-PCR, a newly developed replication reaction using polymerase blocking. The barcodes are recognized by hybridization to surface attached probes and are directly detected by the semiconductor device. PMID:24569823

A Tool for Investigating Asthma and COPD Exacerbations: A Newly Manufactured and Well Characterised GMP Wild-Type Human Rhinovirus for Use in the Human Viral Challenge Model

PubMed Central

Fullen, Daniel J.; Murray, Bryan; Mori, Julie; Catchpole, Andrew; Borley, Daryl W.; Murray, Edward J.; Balaratnam, Ganesh; Gilbert, Anthony; Mann, Alex; Hughes, Fiona; Lambkin-Williams, Rob

2016-01-01

Background Human Rhinovirus infection is an important precursor to asthma and chronic obstructive pulmonary disease exacerbations and the Human Viral Challenge model may provide a powerful tool in studying these and other chronic respiratory diseases. In this study we have reported the production and human characterisation of a new Wild-Type HRV-16 challenge virus produced specifically for this purpose. Methods and Stock Development A HRV-16 isolate from an 18 year old experimentally infected healthy female volunteer (University of Virginia Children’s Hospital, USA) was obtained with appropriate medical history and consent. We manufactured a new HRV-16 stock by minimal passage in a WI-38 cell line under Good Manufacturing Practice conditions. Having first subjected the stock to rigorous adventitious agent testing and determining the virus suitability for human use, we conducted an initial safety and pathogenicity clinical study in adult volunteers in our dedicated clinical quarantine facility in London. Human Challenge and Conclusions In this study we have demonstrated the new Wild-Type HRV-16 Challenge Virus to be both safe and pathogenic, causing an appropriate level of disease in experimentally inoculated healthy adult volunteers. Furthermore, by inoculating volunteers with a range of different inoculum titres, we have established the minimum inoculum titre required to achieve reproducible disease. We have demonstrated that although inoculation titres as low as 1 TCID50 can produce relatively high infection rates, the optimal titre for progression with future HRV challenge model development with this virus stock was 10 TCID50. Studies currently underway are evaluating the use of this virus as a challenge agent in asthmatics. Trial Registration ClinicalTrials.gov NCT02522832 PMID:27936016

Inverse Association of Plasma Chromium Levels with Newly Diagnosed Type 2 Diabetes: A Case-Control Study

PubMed Central

Chen, Sijing; Jin, Xiaoling; Shan, Zhilei; Li, Shuzhen; Yin, Jiawei; Sun, Taoping; Luo, Cheng; Yang, Wei; Yao, Ping; Yu, Kaifeng; Zhang, Yan; Cheng, Qian; Cheng, Jinquan; Bao, Wei; Liu, Liegang

2017-01-01

Chromium has long been known as an enhancer of insulin action. However, the role of chromium in the development of type 2 diabetes mellitus (T2DM) in humans remains controversial. The current study aimed to examine the associations of plasma chromium levels with T2DM and pre-diabetes mellitus (pre-DM). We conducted a case-control study involving 1471 patients with newly diagnosed T2DM, 682 individuals with newly diagnosed pre-DM, and 2290 individuals with normal glucose tolerance in a Chinese population from 2009 to 2014. Plasma chromium was measured by inductively coupled plasma mass spectrometry. Plasma chromium levels were lower in the T2DM and pre-DM groups than in the control group (median: 3.68 μg/L, 3.61 μg/L, 3.97 μg/L, respectively, p < 0.001). After adjustment for potential confounding factors, the odds ratios (95% confidence interval) for T2DM across increasing quartiles of plasma chromium levels were 1 (referent), 0.67 (0.55–0.83), 0.64 (0.51–0.79), and 0.58 (0.46–0.73), respectively (p for trend <0.001). The corresponding odds ratios (95% confidence interval) for pre-DM were 1 (referent), 0.70 (0.54–0.91), 0.67 (0.52–0.88), and 0.58 (0.43–0.78), respectively (p for trend < 0.001). Our results indicated that plasma chromium concentrations were inversely associated with T2DM and pre-DM in Chinese adults. PMID:28304331

Inverse Association of Plasma Chromium Levels with Newly Diagnosed Type 2 Diabetes: A Case-Control Study.

PubMed

Chen, Sijing; Jin, Xiaoling; Shan, Zhilei; Li, Shuzhen; Yin, Jiawei; Sun, Taoping; Luo, Cheng; Yang, Wei; Yao, Ping; Yu, Kaifeng; Zhang, Yan; Cheng, Qian; Cheng, Jinquan; Bao, Wei; Liu, Liegang

2017-03-17

Chromium has long been known as an enhancer of insulin action. However, the role of chromium in the development of type 2 diabetes mellitus (T2DM) in humans remains controversial. The current study aimed to examine the associations of plasma chromium levels with T2DM and pre-diabetes mellitus (pre-DM). We conducted a case-control study involving 1471 patients with newly diagnosed T2DM, 682 individuals with newly diagnosed pre-DM, and 2290 individuals with normal glucose tolerance in a Chinese population from 2009 to 2014. Plasma chromium was measured by inductively coupled plasma mass spectrometry. Plasma chromium levels were lower in the T2DM and pre-DM groups than in the control group (median: 3.68 μg/L, 3.61 μg/L, 3.97 μg/L, respectively, p < 0.001). After adjustment for potential confounding factors, the odds ratios (95% confidence interval) for T2DM across increasing quartiles of plasma chromium levels were 1 (referent), 0.67 (0.55-0.83), 0.64 (0.51-0.79), and 0.58 (0.46-0.73), respectively ( p for trend <0.001). The corresponding odds ratios (95% confidence interval) for pre-DM were 1 (referent), 0.70 (0.54-0.91), 0.67 (0.52-0.88), and 0.58 (0.43-0.78), respectively ( p for trend < 0.001). Our results indicated that plasma chromium concentrations were inversely associated with T2DM and pre-DM in Chinese adults.

A newly synthesized macakurzin C-derivative attenuates acute and chronic skin inflammation: The Nrf2/heme oxygenase signaling as a potential target

DOE Office of Scientific and Technical Information (OSTI.GOV)

Akram, Muhammad

Impaired immune responses in skin play a pivotal role in the development and progression of chemical-associated inflammatory skin disorders. In this study, we synthesized new flavonoid derivatives from macakurzin C, and identified in vitro and in vivo efficacy of a potent anti-inflammatory flavonoid, Compound 14 (CPD 14), with its underlying mechanisms. In lipopolysaccharide (LPS)-stimulated murine macrophages and IFN-γ/TNF-α-stimulated human keratinocytes, CPD 14 significantly inhibited the release of inflammatory mediators including nitric oxide (NO), prostaglandins, and cytokines (IC{sub 50} for NO inhibition in macrophages: 4.61 μM). Attenuated NF-κB signaling and activated Nrf2/HO-1 pathway were responsible for the anti-inflammatory effects of CPDmore » 14. The in vivo relevance was examined in phorbol 12-myristate 13-acetate (TPA)-induced acute skin inflammation and oxazolone-induced atopic dermatitis models. Topically applied CPD 14 significantly protected both irritation- and sensitization-associated skin inflammation by suppressing the expression of inflammatory mediators. In summary, we demonstrated that a newly synthesized flavonoid, CPD 14, has potent inhibitory effects on skin inflammation, suggesting it is a potential therapeutic candidate to treat skin disorders associated with excessive inflammation. - Highlights: • An anti-inflammatory flavonoid CPD 14 was newly synthesized from macakurzin C. • CPD 14 potently inhibited inflammatory reaction in keratinocytes and macrophages. • Dermal toxicity by irritation or sensitization in rats was protected by CPD 14. • Attenuated NF-κB and activated Nrf2/HO-1 were main mechanisms of CPD 14 action.« less

Impact of Cigarette Smoke on the Human and Mouse Lungs: A Gene-Expression Comparison Study

PubMed Central

Morissette, Mathieu C.; Lamontagne, Maxime; Bérubé, Jean-Christophe; Gaschler, Gordon; Williams, Andrew; Yauk, Carole; Couture, Christian; Laviolette, Michel; Hogg, James C.; Timens, Wim; Halappanavar, Sabina; Stampfli, Martin R.; Bossé, Yohan

2014-01-01

Cigarette smoke is well known for its adverse effects on human health, especially on the lungs. Basic research is essential to identify the mechanisms involved in the development of cigarette smoke-related diseases, but translation of new findings from pre-clinical models to the clinic remains difficult. In the present study, we aimed at comparing the gene expression signature between the lungs of human smokers and mice exposed to cigarette smoke to identify the similarities and differences. Using human and mouse whole-genome gene expression arrays, changes in gene expression, signaling pathways and biological functions were assessed. We found that genes significantly modulated by cigarette smoke in humans were enriched for genes modulated by cigarette smoke in mice, suggesting a similar response of both species. Sixteen smoking-induced genes were in common between humans and mice including six newly reported to be modulated by cigarette smoke. In addition, we identified a new conserved pulmonary response to cigarette smoke in the induction of phospholipid metabolism/degradation pathways. Finally, the majority of biological functions modulated by cigarette smoke in humans were also affected in mice. Altogether, the present study provides information on similarities and differences in lung gene expression response to cigarette smoke that exist between human and mouse. Our results foster the idea that animal models should be used to study the involvement of pathways rather than single genes in human diseases. PMID:24663285

"Sebocytes' makeup": novel mechanisms and concepts in the physiology of the human sebaceous glands.

PubMed

Tóth, Balázs I; Oláh, Attila; Szöllosi, Attila G; Czifra, Gabriella; Bíró, Tamás

2011-06-01

The pilosebaceous unit of the human skin consists of the hair follicle and the sebaceous gland. Within this "mini-organ", the sebaceous gland has been neglected by the researchers of the field for several decades. Actually, it was labeled as a reminiscence of human development ("a living fossil with a past but no future"), and was thought to solely act as a producer of sebum, a lipid-enriched oily substance which protects our skin (and hence the body) against various insults. However, due to emerging research activities of the past two decades, it has now become evident that the sebaceous gland is not only a "passive" cutaneous "relic" to establish the physico-chemical barrier function of the skin against constant environmental challenges, but it rather functions as an "active" neuro-immuno-endocrine cutaneous organ. This review summarizes recent findings of sebaceous gland research by mainly focusing on newly discovered physiological functions, novel regulatory mechanisms, key events in the pathology of the gland, and future directions in both experimental and clinical dermatology.

Single Cell Analysis of Human RAD18-Dependent DNA Post-Replication Repair by Alkaline Bromodeoxyuridine Comet Assay

PubMed Central

Mórocz, Mónika; Gali, Himabindu; Raskó, István; Downes, C. Stephen; Haracska, Lajos

2013-01-01

Damage to DNA can block replication progression resulting in gaps in the newly synthesized DNA. Cells utilize a number of post-replication repair (PRR) mechanisms such as the RAD18 controlled translesion synthesis or template switching to overcome the discontinuities formed opposite the DNA lesions and to complete DNA replication. Gaining more insights into the role of PRR genes promotes better understanding of DNA damage tolerance and of how their malfunction can lead to increased genome instability and cancer. However, a simple and efficient method to characterise gene specific PRR deficiencies at a single cell level has not been developed. Here we describe the so named BrdU comet PRR assay to test the contribution of human RAD18 to PRR at a single cell level, by which we kinetically characterized the consequences of the deletion of human RAD18 on the replication of UV-damaged DNA. Moreover, we demonstrate the capability of our method to evaluate PRR at a single cell level in unsynchronized cell population. PMID:23936422

Junctional and allele-specific residues are critical for MERS-CoV neutralization by an exceptionally potent germline-like antibody

DOE PAGES

Ying, Tianlei; Prabakaran, Ponraj; Du, Lanying; ...

2015-09-15

The MERS-CoV is an emerging virus, which already infected more than 1,300 humans with high (~36%) mortality. Here, we show that m336, an exceptionally potent human anti-MERS-CoV antibody, is almost germline with only one somatic mutation in the heavy chain. The structure of Fab m336 in complex with the MERS-CoV receptor-binding domain reveals that its IGHV1-69-derived heavy chain provides more than 85% binding surface and that its epitope almost completely overlaps with the receptor-binding site. Analysis of antibodies from 69 healthy humans suggests an important role of the V(D)J recombination-generated junctional and allele-specific residues for achieving high affinity of bindingmore » at such low levels of somatic hypermutation. Our results also have important implications for development of vaccine immunogens based on the newly identified m336 epitope as well as for elucidation of mechanisms of neutralization by m336-like antibodies and their elicitation in vivo.« less

Infection Risk for Persons Exposed to Highly Pathogenic Avian Influenza A H5 Virus-Infected Birds, United States, December 2014-March 2015.

PubMed

Arriola, Carmen S; Nelson, Deborah I; Deliberto, Thomas J; Blanton, Lenee; Kniss, Krista; Levine, Min Z; Trock, Susan C; Finelli, Lyn; Jhung, Michael A

2015-12-01

Newly emerged highly pathogenic avian influenza (HPAI) A H5 viruses have caused outbreaks among birds in the United States. These viruses differ genetically from HPAI H5 viruses that previously caused human illness, most notably in Asia and Africa. To assess the risk for animal-to-human HPAI H5 virus transmission in the United States, we determined the number of persons with self-reported exposure to infected birds, the number with an acute respiratory infection (ARI) during a 10-day postexposure period, and the number with ARI who tested positive for influenza by real-time reverse transcription PCR or serologic testing for each outbreak during December 15, 2014-March 31, 2015. During 60 outbreaks in 13 states, a total of 164 persons were exposed to infected birds. ARI developed in 5 of these persons within 10 days of exposure. H5 influenza virus infection was not identified in any persons with ARI, suggesting a low risk for animal-to-human HPAI H5 virus transmission.

What is the true clinical relevance of Simkania negevensis and other emerging Chlamydiales members?

PubMed

Vouga, M; Kebbi-Beghdadi, C; Liénard, J; Baskin, L; Baud, D; Greub, G

2018-05-01

Waddlia   chondrophila and Simkania negevensis are emerging Chlamydia- related bacteria. Similar to the pathogenic organisms Chlamydia pneumoniae and Chlamydia trachomatis, these emerging bacteria are implicated in human genital infections and respiratory diseases. We used a screening strategy based on a newly developed S. negevensis -specific quantitative real-time PCR (qPCR) and a pan- Chlamydiales qPCR. We could not detect S. negevensis in 458 respiratory, genitourinary, cardiac and hepatic samples tested. One urethral swab was positive for W. chondrophila. We observed a low prevalence of Chlamydiales in respiratory samples (1/200, 0.5%), which suggests that C. pneumoniae is an uncommon respiratory pathogen. Furthermore, we screened 414 human serum samples from Switzerland, England and Israel and observed a low prevalence (<1%) of exposure to S. negevensis. Conversely, humans were commonly exposed to W. chondrophila, with seroprevalences ranging from 8.6% to 32.5%. S. negevensis is not a clinically relevant pathogen, but further research investigating the role of W. chondrophila is needed.

Ex vivo study of the home-use TriPollar RF device using an experimental human skin model.

PubMed

Boisnic, Sylvie; Branchet, Marie Christine

2010-09-01

A wide variety of professional radio frequency (RF) aesthetic treatments for anti-aging are available aiming at skin tightening. A new home-use RF device for facial treatments has recently been developed based on TriPollar technology. To evaluate the mechanism of the new home-use device, in the process of collagen remodeling, using an ex vivo skin model. Human skin samples were collected in order to evaluate the anti-aging effect of a home-use device for facial treatments on an ex vivo human skin model. Skin tightening was evaluated by dermal histology, quantitative analysis of collagen fibers and dosage of collagen synthesis. Significant collagen remodeling following RF treatment with the device was found in the superficial and mid-deep dermis. Biochemical measurement of newly synthesized collagen showed an increase of 41% in the treated samples as compared to UV-aged control samples. The new home-use device has been demonstrated to affect significant collagen remodeling, in terms of the structural and biochemical improvement of dermal collagen on treated skin samples.

HtrA3 as an Early Marker for Preeclampsia: Specific Monoclonal Antibodies and Sensitive High-Throughput Assays for Serum Screening

PubMed Central

Dynon, Kemperly; Heng, Sophea; Puryer, Michelle; Li, Ying; Walton, Kelly; Endo, Yaeta; Nie, Guiying

2012-01-01

Mammalian HtrA3 (high temperature requirement A3) is a serine protease of the HtrA family. It has two isoforms [long (HtrA3-L) and short (HtrA3-S)] and is important for placental development and cancer progression. Recently, HtrA3 was identified as a potential diagnostic marker for early detection of preeclampsia, a life-threatening pregnancy-specific disorder. Currently there are no high-throughput assays available to detect HtrA3 in human serum. In this study we generated and fully tested a panel of five HtrA3 mouse monoclonal antibodies (mAbs). Three mAbs recognised both HtrA3-L and HtrA3-S and the other two detected HtrA3-L only. All five mAbs were highly specific to HtrA3 and applicable in western blotting and immunohistochemical analysis of endogenous HtrA3 proteins in the mouse and human tissues. Amplified luminescent proximity homogeneous assays-linked immunosorbent assays (AlphaLISAs), were developed to detect HtrA3 isoforms in picomolar levels in serum. The HtrA3 AlphaLISA detected significantly higher serum levels of HtrA3 in women at 13–14 weeks of gestation who subsequently developed preeclampsia compared to gestational-age matched controls. These HtrA3 mAbs are valuable for the development of immunoassays and characterisation of HtrA3 isoform-specific biology. The newly developed HtrA3 AlphaLISA assays are suitable for large scale screening of human serum. PMID:23049902

The automotive application of discontinuously reinforced TiB-Ti composites

NASA Astrophysics Data System (ADS)

Saito, Takashi

2004-05-01

In 1998, Toyota Motor Corporation adopted intake valves and exhaust valves made of titanium-based alloys for the engine of its Altezza. Both valves were manufactured via a newly developed cost-effective powder metallurgy process. The exhaust valve is made of a newly developed titanium metal-matrix composite (MMC). The valve has achieved sufficient durability and reliability with a manufacturing cost acceptable for the mass-produced automobile engine components.

Fast-Track Teacher Recruitment.

ERIC Educational Resources Information Center

Grant, Franklin Dean

2001-01-01

Schools need a Renaissance human-resources director to implement strategic staffing and fast-track teacher-recruitment plans. The HR director must attend to customer satisfaction, candidate supply, web-based recruitment possibilities, stabilization of newly hired staff, retention of veteran staff, utilization of retired employees, and latest…

Advancing Humanity through Honors

ERIC Educational Resources Information Center

Rao, Michael

2015-01-01

In February of 1967, newly elected Governor Ronald Reagan delivered a speech about California's austere budget in which he chided the "intellectual luxury" of higher education as something that could lead to "economic ruin" if unchecked. "Taxpayers shouldn't be subsidizing intellectual curiosity," Gov. Reagan decreed.…

A model for mentoring newly-appointed nurse educators in nursing education institutions in South Africa.

PubMed

Seekoe, Eunice

2014-04-24

South Africa transformed higher education through the enactment of the Higher Education Act (No. 101 of 1997). The researcher identified the need to develop a model for the mentoring of newly-appointed nurse educators in nursing education institutions in South Africa.  To develop and describe the model for mentoring newly-appointed nurse educators in nursing education institutions in South Africa.  A qualitative and theory-generating design was used (following empirical findings regarding needs analysis) in order to develop the model. The conceptualisation of the framework focused on the context, content, process and the theoretical domains that influenced the model. Ideas from different theories were borrowed from and integrated with the literature and deductive and inductive strategies were applied.  The structure of the model is multidimensional and complex in nature (macro, mesoand micro) based on the philosophy of reflective practice, competency-based practice andcritical learning theories. The assumptions are in relation to stakeholders, context, mentoring, outcome, process and dynamic. The stakeholders are the mentor and mentee within an interactive participatory relationship. The mentoring takes place within the process with a sequence of activities such as relationship building, development, engagement, reflective process and assessment. Capacity building and empowerment are outcomes of mentoring driven by motivation.  The implication for nurse managers is that the model can be used to develop mentoring programmes for newly-appointed nurse educators.

Ensemble variant interpretation methods to predict enzyme activity and assign pathogenicity in the CAGI4 NAGLU (Human N-acetyl-glucosaminidase) and UBE2I (Human SUMO-ligase) challenges.

PubMed

Yin, Yizhou; Kundu, Kunal; Pal, Lipika R; Moult, John

2017-09-01

CAGI (Critical Assessment of Genome Interpretation) conducts community experiments to determine the state of the art in relating genotype to phenotype. Here, we report results obtained using newly developed ensemble methods to address two CAGI4 challenges: enzyme activity for population missense variants found in NAGLU (Human N-acetyl-glucosaminidase) and random missense mutations in Human UBE2I (Human SUMO E2 ligase), assayed in a high-throughput competitive yeast complementation procedure. The ensemble methods are effective, ranked second for SUMO-ligase and third for NAGLU, according to the CAGI independent assessors. However, in common with other methods used in CAGI, there are large discrepancies between predicted and experimental activities for a subset of variants. Analysis of the structural context provides some insight into these. Post-challenge analysis shows that the ensemble methods are also effective at assigning pathogenicity for the NAGLU variants. In the clinic, providing an estimate of the reliability of pathogenic assignments is the key. We have also used the NAGLU dataset to show that ensemble methods have considerable potential for this task, and are already reliable enough for use with a subset of mutations. © 2017 Wiley Periodicals, Inc.

A molecular arms race between host innate antiviral response and emerging human coronaviruses.

PubMed

Wong, Lok-Yin Roy; Lui, Pak-Yin; Jin, Dong-Yan

2016-02-01

Coronaviruses have been closely related with mankind for thousands of years. Community-acquired human coronaviruses have long been recognized to cause common cold. However, zoonotic coronaviruses are now becoming more a global concern with the discovery of highly pathogenic severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronaviruses causing severe respiratory diseases. Infections by these emerging human coronaviruses are characterized by less robust interferon production. Treatment of patients with recombinant interferon regimen promises beneficial outcomes, suggesting that compromised interferon expression might contribute at least partially to the severity of disease. The mechanisms by which coronaviruses evade host innate antiviral response are under intense investigations. This review focuses on the fierce arms race between host innate antiviral immunity and emerging human coronaviruses. Particularly, the host pathogen recognition receptors and the signal transduction pathways to mount an effective antiviral response against SARS and MERS coronavirus infection are discussed. On the other hand, the counter-measures evolved by SARS and MERS coronaviruses to circumvent host defense are also dissected. With a better understanding of the dynamic interaction between host and coronaviruses, it is hoped that insights on the pathogenesis of newly-identified highly pathogenic human coronaviruses and new strategies in antiviral development can be derived.

Endothelial progenitor cells regenerate infracted myocardium with neovascularisation development.

PubMed

Abd El Aziz, M T; Abd El Nabi, E A; Abd El Hamid, M; Sabry, D; Atta, H M; Rahed, L A; Shamaa, A; Mahfouz, S; Taha, F M; Elrefaay, S; Gharib, D M; Elsetohy, Khaled A

2015-03-01

We achieved possibility of isolation, characterization human umbilical cord blood endothelial progenitor cells (EPCs), examination potency of EPCs to form new blood vessels and differentiation into cardiomyoctes in canines with acute myocardial infarction (AMI). EPCs were separated and cultured from umbilical cord blood. Their phenotypes were confirmed by uptake of double stains dioctadecyl tetramethylindocarbocyanine-labeled acetylated LDL and FITC-labeled Ulex europaeus agglutinin 1 (DILDL-UEA-1). EPCs of cord blood were counted. Human VEGFR-2 and eNOS from the cultured EPCs were assessed by qPCR. Human EPCs was transplanted intramyocardially in canines with AMI. ECG and cardiac enzymes (CK-MB and Troponin I) were measured to assess severity of cellular damage. Histopathology was done to assess neovascularisation. Immunostaining was done to detect EPCs transdifferentiation into cardiomyocytes in peri-infarct cardiac tissue. qPCR for human genes (hVEGFR-2, and eNOS) was done to assess homing and angiogenic function of transplanted EPCs. Cultured human cord blood exhibited an increased number of EPCs and significant high expression of hVEGFR-2 and eNOS genes in the culture cells. Histopathology showed increased neovascularization and immunostaining showed presence of EPCs newly differentiated into cardiomyocyte-like cells. Our findings suggested that hEPCs can mediate angiogenesis and differentiate into cardiomyoctes in canines with AMI.

Biological and Host Range Studies with Bagous affinis, An Indian Weevil that Destroys Hydrilla Tubers. Aquatic Plant Control Research Program.

DTIC Science & Technology

1994-12-01

three times with newly emerged adults and three times with adults at least a month old. Treatments were (a) four hydrilla sprigs, (b) four hydrilla...Methods conducted to determine if feeding on nonhost plants stimulated the develop- ment of flight muscles. Newly emerged females were held in a plastic...Fecundity and adult longevity A fecundity and adult longevity test was conducted with newly emerged adults. Adults were held initially with moist paper

Chimpanzee and human Y chromosomes are remarkably divergent in structure and gene content.

PubMed

Hughes, Jennifer F; Skaletsky, Helen; Pyntikova, Tatyana; Graves, Tina A; van Daalen, Saskia K M; Minx, Patrick J; Fulton, Robert S; McGrath, Sean D; Locke, Devin P; Friedman, Cynthia; Trask, Barbara J; Mardis, Elaine R; Warren, Wesley C; Repping, Sjoerd; Rozen, Steve; Wilson, Richard K; Page, David C

2010-01-28

The human Y chromosome began to evolve from an autosome hundreds of millions of years ago, acquiring a sex-determining function and undergoing a series of inversions that suppressed crossing over with the X chromosome. Little is known about the recent evolution of the Y chromosome because only the human Y chromosome has been fully sequenced. Prevailing theories hold that Y chromosomes evolve by gene loss, the pace of which slows over time, eventually leading to a paucity of genes, and stasis. These theories have been buttressed by partial sequence data from newly emergent plant and animal Y chromosomes, but they have not been tested in older, highly evolved Y chromosomes such as that of humans. Here we finished sequencing of the male-specific region of the Y chromosome (MSY) in our closest living relative, the chimpanzee, achieving levels of accuracy and completion previously reached for the human MSY. By comparing the MSYs of the two species we show that they differ radically in sequence structure and gene content, indicating rapid evolution during the past 6 million years. The chimpanzee MSY contains twice as many massive palindromes as the human MSY, yet it has lost large fractions of the MSY protein-coding genes and gene families present in the last common ancestor. We suggest that the extraordinary divergence of the chimpanzee and human MSYs was driven by four synergistic factors: the prominent role of the MSY in sperm production, 'genetic hitchhiking' effects in the absence of meiotic crossing over, frequent ectopic recombination within the MSY, and species differences in mating behaviour. Although genetic decay may be the principal dynamic in the evolution of newly emergent Y chromosomes, wholesale renovation is the paramount theme in the continuing evolution of chimpanzee, human and perhaps other older MSYs.

The requirement for freshly isolated human colorectal cancer (CRC) cells in isolating CRC stem cells.

PubMed

Fan, F; Bellister, S; Lu, J; Ye, X; Boulbes, D R; Tozzi, F; Sceusi, E; Kopetz, S; Tian, F; Xia, L; Zhou, Y; Bhattacharya, R; Ellis, L M

2015-02-03

Isolation of colorectal cancer (CRC) cell populations enriched for cancer stem cells (CSCs) may facilitate target identification. There is no consensus regarding the best methods for isolating CRC stem cells (CRC-SCs). We determined the suitability of various cellular models and various stem cell markers for the isolation of CRC-SCs. Established human CRC cell lines, established CRC cell lines passaged through mice, patient-derived xenograft (PDX)-derived cells, early passage/newly established cell lines, and cells directly from clinical specimens were studied. Cells were FAC-sorted for the CRC-SC markers CD44, CD133, and aldehyde dehydrogenase (ALDH). Sphere formation and in vivo tumorigenicity studies were used to validate CRC-SC enrichment. None of the markers studied in established cell lines, grown either in vitro or in vivo, consistently enriched for CRC-SCs. In the three other cellular models, CD44 and CD133 did not reliably enrich for stemness. In contrast, freshly isolated PDX-derived cells or early passage/newly established CRC cell lines with high ALDH activity formed spheres in vitro and enhanced tumorigenicity in vivo, whereas cells with low ALDH activity did not. PDX-derived cells, early passages/newly established CRC cell lines and cells from clinical specimen with high ALDH activity can be used to identify CRC-SC-enriched populations. Established CRC cell lines should not be used to isolate CSCs.

Nonsecreted cytoplasmic alpha-fetoprotein: a newly discovered role in intracellular signaling and regulation. An update and commentary.

PubMed

Mizejewski, G J

2015-12-01

The concept of a non-secreted cytoplasmic-bound form of alpha-fetoprotein is not a new notion in AFP biological activities. Cytoplasmic AFP (CyAFP) is a long known but forgotten protein in search of a function other than a histochemical biomarker. In this report, CyAFP is presented as an "old" protein with a newly described intracellular function. In 1976, CyAFP was shown to be a product of hepatoma cells utilizing 14Cleucine incorporation and demonstrated by autoradiographic procedures. The synthesis of CyAFP without secretion was demonstrated to occur in both malignant and non-malignant cells encompassing hepatomas, ascite fluid cells, immature rodent uterus, MCF-7 breast cancers, and cytosols from human breast cancer patients. Using computer protein matching and alignments in AFP versus members of the nuclear receptor superfamily, a consecutive series of leucine zipper (heptad) repeats in AFP was previously reported, suggesting the possibility for protein-to-protein interactions. The potential for heptad heterodimerization between protein-binding partners provided the rationale for proposing that CyAFP might have the capability to form molecular hetero-complexes with cytoplasmic based transcription factors. More recent investigations have now provided experimental evidence that CyAFP is capable of colocalizing and interacting with transcription-associated factors. Such proteins can modulate intracellular signaling leading to regulation of transcription factors and initiation of growth in human cancer cells. Although circulating serum AFP is known as a growth-enhancing factor during development, cytoplasmic AFP has a lethal role in the oncogenesis, growth, and metastasis of adult liver cancer.

A comparison of the efficacy of newly developed reversible inhibitors of acetylcholinesterase with commonly used pyridostigmine as pharmacological pre-treatment of soman-poisoned mice.

PubMed

Kassa, Jiri; Musilek, Kamil; Koomlova, Marketa; Bajgar, Jiri

2012-04-01

The ability of three newly developed reversible inhibitors of acetylcholinesterase (AChE) (K298, K344 and K474) and currently available carbamate pyridostigmine to increase the resistance of mice against soman and the efficacy of antidotal treatment of soman-poisoned mice was compared. Neither pyridostigmine nor new reversible inhibitors of AChE were able to increase the LD(50) value of soman. Thus, the pharmacological pre-treatment with pyridostigmine or newly synthesized inhibitors of AChE was not able to protect mice against soman-induced lethal acute toxicity. The pharmacological pre-treatment with pyridostigmine alone or with K474 was able to slightly increase the efficacy of antidotal treatment (the oxime HI-6 in combination with atropine) of soman-poisoned mice, but the increase in the efficacy of antidotal treatment was not significant. The other newly developed reversible inhibitors of AChF (K298, K344) were completely ineffective. These findings demonstrate that pharmacological pre-treatment of soman-poisoned mice with tested reversible inhibitors of AChF is not promising. © 2011 The Authors. Basic & Clinical Pharmacology & Toxicology © 2011 Nordic Pharmacological Society.

Determination of metabolites of diosmetin-7-O-glucoside by a newly isolated Escherichia coli from human gut using UPLC-Q-TOF/MS.

PubMed

Zhao, Min; Du, Leyue; Tao, Jinhua; Qian, Dawei; Shang, Er-xin; Jiang, Shu; Guo, Jianming; Liu, Pei; Su, Shu-lan; Duan, Jin-ao

2014-11-26

Different human intestinal bacteria were isolated and screened for their ability to transform diosmetin-7-O-glucoside. A Gram-negative anaerobic bacterium, strain 4, capable of metabolizing diosmetin-7-O-glucoside was newly isolated. Its 16S rRNA gene sequence displayed 99% similarity with that of Escherichia. Then strain 4 was identified as a species of the genus Escherichia and was named Escherichia sp. 4. Additionally, an ultraperformance liquid chromatography/quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF/MS) technique combined with Metabolynx software method was established to screen the metabolites of diosmetin-7-O-glucoside. Comparing the retention time and MS/MS spectrum, three metabolites were detected and tentatively identified. These metabolites were acquired by four proposed metabolic pathways including dehydroxylation, deglycosylation, methylation, and acetylation. Diosmetin-7-O-glucoside was mainly bioconverted to considerable amounts of diosmetin and minor amounts of acacetin by the majority of the isolated intestinal bacteria such as Escherichia sp. 4. Subsequently, several strains could degrade acacetin to produce methylated and acetylated acacetin. The metabolites and metabolic pathways of diosmetin-7-O-glucoside by human intestinal bacterium Escherichia sp. 4 were first investigated.

Development of methods and specifications for the use of inertial profilers and the international roughness index for newly constructed pavement.

DOT National Transportation Integrated Search

2013-06-01

The Indiana Department of Transportation (INDOT) is currently utilizing a profilograph and the profile index for measuring smoothness : assurance for newly constructed pavements. However, there are benefits to implementing a new IRI based smoothness ...

Anti-adhesive effects of a newly developed two-layered gelatin sheet in dogs.

PubMed

Torii, Hiroko; Takagi, Toshitaka; Urabe, Mamoru; Tsujimoto, Hiroyuki; Ozamoto, Yuki; Miyamoto, Hiroe; Ikada, Yoshihito; Hagiwara, Akeo

2017-08-01

Adhesion after pelvic surgery causes infertility, ectopic pregnancy, and ileus or abdominal pain. The materials currently available for clinical use are insufficient. The purpose of this study was to develop an anti-adhesive material that overcomes the limitations of conventional anti-adhesive agents. The adhesion prevention effects of three methods - a two-layered sheet composed of gelatin film and gelatin sponge, Seprafilm and INTERCEED - were evaluated in 37 dogs. Anti-adhesive effects were investigated macroscopically and microscopically in a cauterized uterus adhesion model. Cell growth on the materials in vitro using human peritoneal mesothelial cells, fibroblasts and uterine smooth muscle cells were also evaluated. The two-layered gelatin sheet had significantly superior anti-adhesive effects compared to the conventional materials (Seprafilm and INTERCEED). A single-cell layer of mature mesothelium formed three weeks after surgery in the gelatin group. Peritoneum regeneration in the Seprafilm and INTERCEED groups was delayed and incomplete in the early phase. Little inflammation around the materials occurred and cell growth was significantly proliferated with the gelatin sheet. The anti-adhesive effects of a two-layered gelatin sheet were superior to conventional agents in a cauterized canine uterus model, demonstrating early regeneration of the peritoneum, little inflammation and material endurance. The newly developed two-layered gelatin sheet is a useful option as an anti-adhesive agent for deeply injured and hemorrhagic sites. © 2017 The Authors. Journal of Obstetrics and Gynaecology Research published by John Wiley & Sons Australia, Ltd on behalf of Japan Society of Obstetrics and Gynecology.

Professional socialization: the key to survival as a newly qualified nurse.

PubMed

Mooney, Mary

2007-04-01

The impact and prevalence of professional socialization in nursing has been written about extensively. Despite the many positive developments that have taken place in nursing within the past decade, the role of professional socialization remains heavily weighted and is of particular significance to those nurses who are newly qualified. The account given by newly registered nurses in this study demonstrates that their ability and willingness to become professionally socialized determines their ease of survival at clinical level. Twelve newly qualified Irish nurses, from two separate cohorts, were interviewed to ascertain their perceptions of becoming newly qualified nurses. A grounded theory approach was used and data were analysed using thematic analysis. A category that emerged was linked very strongly with professional socialization. The respondents did not refer to professional socialization per se, but through the coding process this emerged as the linchpin of the discussion.

Clinical Prediction Model for Time in Therapeutic Range While on Warfarin in Newly Diagnosed Atrial Fibrillation.

PubMed

Williams, Brent A; Evans, Michael A; Honushefsky, Ashley M; Berger, Peter B

2017-10-12

Though warfarin has historically been the primary oral anticoagulant for stroke prevention in newly diagnosed atrial fibrillation (AF), several new direct oral anticoagulants may be preferred when anticoagulation control with warfarin is expected to be poor. This study developed a prediction model for time in therapeutic range (TTR) among newly diagnosed AF patients on newly initiated warfarin as a tool to assist decision making between warfarin and direct oral anticoagulants. This electronic medical record-based, retrospective study included newly diagnosed, nonvalvular AF patients with no recent warfarin exposure receiving primary care services through a large healthcare system in rural Pennsylvania. TTR was estimated as the percentage of time international normalized ratio measurements were between 2.0 and 3.0 during the first year following warfarin initiation. Candidate predictors of TTR were chosen from data elements collected during usual clinical care. A TTR prediction model was developed and temporally validated and its predictive performance was compared with the SAMe-TT 2 R 2 score (sex, age, medical history, treatment, tobacco, race) using R 2 and c-statistics. A total of 7877 newly diagnosed AF patients met study inclusion criteria. Median (interquartile range) TTR within the first year of starting warfarin was 51% (32, 67). Of 85 candidate predictors evaluated, 15 were included in the final validated model with an R 2 of 15.4%. The proposed model showed better predictive performance than the SAMe-TT 2 R 2 score ( R 2 =3.0%). The proposed prediction model may assist decision making on the proper mode of oral anticoagulant among newly diagnosed AF patients. However, predicting TTR on warfarin remains challenging. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Natural Organohalogens: A New Frontier for Medicinal Agents?

ERIC Educational Resources Information Center

Gribble, Gordon W.

2004-01-01

Newly discovered biogenic organo halogens with an emphasis on the biologically active examples from marine organisms, bacteria, terrestrial plants and higher life forms, including humans, are focused. Organohalogen compounds represent a valuable and expanding class of natural products, in many cases boasting exceptional biological activity.

Determination of capsinoids by HPLC-DAD in Capsicum species

USDA-ARS?s Scientific Manuscript database

Capsicum fruit contain a number of phytochemicals, including the newly characterized capsinoids that have been shown to have positive effects on human health (10-15). Closely related to the pungent capsaicinoids, the non-pungent casinoids exhibit antioxidant activity, promote energy metabolism and r...

Preparing Protocols for Institutional Review Boards.

ERIC Educational Resources Information Center

Lyons, Charles M.

1983-01-01

Introduces the process by which Institutional Review Boards (IRBs) review proposals for research involving human subjects. Describes the composition of IRBs. Presents the Nuremberg code, the elements of informed consent, the judging criteria for proposals, and a sample protocol format. References newly published regulations governing research with…

Synthesis and in vitro antiproliferative and antibacterial activity of new thiazolidine-2,4-dione derivatives.

PubMed

Trotsko, Nazar; Przekora, Agata; Zalewska, Justyna; Ginalska, Grażyna; Paneth, Agata; Wujec, Monika

2018-12-01

In our present research, we synthesised new thiazolidine-2,4-diones (12-28). All the newly synthesised compounds were evaluated for antiproliferative and antibacterial activity. Antiproliferative evaluation was carried out using normal human skin fibroblasts and tumour cell lines: A549, HepG2, and MCF-7. The IC 50 values were determined for tested compounds revealing antiproliferative activity. Moreover, safety index (SI) was calculated. Among all tested derivatives, the compound 18 revealed the highest antiproliferative activity against human lung, breast, and liver cancer cells. More importantly, the derivative 18 showed meaningfully lower IC 50 values when compared to the reference substance, irinotecan, and relatively high SI values. Moreover, newly synthesised compounds were screened for the bacteria growth inhibition in vitro. According to our screening results, most active compound was the derivative 18 against Gram-positive bacteria. Therefore, it may be implied that the novel compound 18 appears to be a very promising agent for anticancer treatment.

The science and fiction of emerging rickettsioses.

PubMed

Paddock, Christopher D

2009-05-01

As newly recognized rickettsial diseases and rickettsial pathogens increase in scope and magnitude, several elements related to the concept of emerging rickettsioses deserve consideration. Newly identified rickettsiae may be mildly pathogenic, or perhaps even nonpathogenic, and have little direct impact on human or animal health, yet nonetheless wield considerable influence on the epidemiology and ecology of historically recognized diseases. In this context "new" rickettsioses provide a lens through which "old" rickettsioses are more accurately represented. Predicting pathogen from nonpathogen is not an exact science, particularly as so few rickettsiae have been broadly accepted as nonpathogenic by contemporary rickettsiologists. However, various factors relating to specific physiologic requirements and molecular machinery of the particular rickettsia, as well as characteristics of its invertebrate host that either position or exclude the rickettsia from infecting a human host, must be considered. Close inspection of mild or atypical forms of historically recognized rickettsioses and a greater emphasis on culture- and molecular-based diagnostic techniques are the keys to identifying future rickettsial agents of disease.

Reduced virus replication, proinflammatory cytokine production, and delayed macrophage cell death in human PBMCs infected with the newly discovered Bundibugyo ebolavirus relative to Zaire ebolavirus.

PubMed

Gupta, Manisha; Goldsmith, Cynthia S; Metcalfe, Maureen G; Spiropoulou, Christina F; Spipopoulou, Christina F; Rollin, Pierre E

2010-06-20

Bundibugyo ebolavirus is a newly identified Ebolavirus species. The virus was responsible for a recent hemorrhagic fever outbreak in Uganda with an approximate 30% case fatality rate. In this study, we compared the pathogenesis of Bundibugyo with highly lethal Zaire Ebolavirus by using in vitro human PBMCs. We found that PBMCs infected with Bundibugyo ebolaviruses resulted in 1 to 2 log lower virus yields compared to Zaire ebolavirus and produced 2- to 10-fold lower levels of TNF-alpha, MCP-1, IL-1beta, MIP1-alpha and IL-10 than PBMCs infected with Zaire ebolavirus. In addition, flow cytometric studies have shown lower levels and delay of the macrophage cell death in Bundibugyo ebolavirus compared to Zaire ebolavirus infection. The findings of slower Bundibugyo ebolavirus replication, lower production of proinflammatory cytokines and delay in macrophage cell death provide insight into the basis of the lower case fatality observed with Bundibugyo ebolavirus. Published by Elsevier Inc.

Synthesis and evaluation of new thiadiazole derivatives as potential inhibitors of human carbonic anhydrase isozymes (hCA-I and hCA-II).

PubMed

Altintop, Mehlika Dilek; Ozdemir, Ahmet; Kucukoglu, Kaan; Turan-Zitouni, Gulhan; Nadaroglu, Hayrunnisa; Kaplancikli, Zafer Asim

2015-02-01

2-[[5-(2,4-Difluoro/dichlorophenylamino)-1,3,4-thiadiazol-2-yl]thio] acetophenone derivatives (3a--s) were designed as human carbonic anhydrase isozymes (hCA-I and hCA-II) inhibitors and synthesized. hCA-I and hCA-II were purified from erythrocyte cells by the affinity chromatography. The inhibitory effects of 18 newly synthesized acetophenones on hydratase activity of these isoenzymes were studied in vitro. The average IC50 values of the new compounds for hydratase activity ranged from 0.033 to 0.14 μM for hCA-I and from 0.030 to 0.11 μM for hCA-II. Among the newly synthesized compounds, 2-[[5-(2,4-dichlorophenylamino)-1,3,4-thiadiazol-2-yl]thio]-4'-bromoacetophenone (3n) can be considered as a promising hCA-II inhibitor owing to its selective and potent inhibitory effect on hCA-II.

A comparison of three approaches for simulating fine-scale surface winds in support of wildland fire management: Part I. Model formulation and comparison against measurements

Treesearch

Jason M. Forthofer; Bret W. Butler; Natalie S. Wagenbrenner

2014-01-01

For this study three types of wind models have been defined for simulating surface wind flow in support of wildland fire management: (1) a uniform wind field (typically acquired from coarse-resolution (,4 km) weather service forecast models); (2) a newly developed mass-conserving model and (3) a newly developed mass and momentumconserving model (referred to as the...

Magnetic Resonance Imaging of Adipose Tissue in Metabolic Dysfunction.

PubMed

Franz, Daniela; Syväri, Jan; Weidlich, Dominik; Baum, Thomas; Rummeny, Ernst J; Karampinos, Dimitrios C

2018-06-06

 Adipose tissue has become an increasingly important tissue target in medicine. It plays a central role in the storage and release of energy throughout the human body and has recently gained interest for its endocrinologic function. Magnetic resonance imaging (MRI) is an established method for quantitative direct evaluation of adipose tissue distribution, and is used increasingly as the modality of choice for metabolic phenotyping. The purpose of this review was the identification and presentation of the currently available literature on MRI of adipose tissue in metabolic dysfunction.  A PubMed (http://www.ncbi.nlm.nih.gov/pubmed) keyword search up to August 2017 without starting date limitation was performed and reference lists of relevant articles were searched.  MRI provides excellent tools for the evaluation of adipose tissue distribution and further characterization of the tissue. Standard as well as newly developed MRI techniques allow a risk stratification for the development of metabolic dysfunction and enable monitoring without the use of ionizing radiation or contrast material.   · Different types of adipose tissue play a crucial role in various types of metabolic dysfunction.. · Magnetic resonance imaging (MRI) is an excellent tool for noninvasive adipose tissue evaluation with respect to distribution, composition and metabolic activity.. · Both standard and newly developed MRI techniques can be used for risk stratification for the development of metabolic dysfunction and allow monitoring without the use of ionizing radiation or contrast material.. · Franz D, Syväri J, Weidlich D et al. Magnetic Resonance Imaging of Adipose Tissue in Metabolic Dysfunction. Fortschr Röntgenstr 2018; DOI: 10.1055/a-0612-8006. © Georg Thieme Verlag KG Stuttgart · New York.

"The only feasible means." The Pentagon's ambivalent relationship with the Nuremberg Code.

PubMed

Moreno, J D

1996-01-01

Convinced that armed conflict with the Soviet Union was all but inevitable, that such conflict would involve unconventional atomic, biological, and chemical warfare, and that research with human subjects was essential to respond to the threat, in the early 1950s the U.S. Department of Defense promulgated a policy governing human experimentation based on the Nuremberg Code. Yet the policymaking process focused on the abstract issue of whether human experiments should go forward at all, ignoring the reality of humans subjects research already under way and leaving unanswered ethical questions about how to conduct such research. Documents newly released to the Advisory Committee on Human Radiation Experiments tell the story of the Pentagon policy.

Psychological characteristics of patients with newly developed psychogenic seizures

PubMed Central

van Merode, T; Twellaar, M; Kotsopoulos, I; Kessels, A; Merckelbach, H; de Krom, M C T F M; Knottnerus, J

2004-01-01

Methods: Using validated scales, 178 patients from the general population diagnosed with newly developed seizures were assessed, at a point in time when the nature of their seizures was yet unknown to either doctors or patients. After standardised neurological examination, 138 patients were diagnosed with non-psychogenic seizures (NPS), while 40 patients were found to have psychogenic seizures (PS). To evaluate possible differences between the genders and the diagnostic groups, univariate analyses of variance were done. Results: PS patients reported significantly more comorbid psychopathological complaints, dissociative experiences, anxiety, and self-reported childhood trauma than NPS patients. In addition, PS patients had lower quality of life ratings than NPS patients. These effects were not modulated by gender. Conclusions: The results of the present study indicate that patients with newly developed PS constitute a group with complex psychopathological features that warrant early detection and treatment. PMID:15258225

Human Urinary Epithelial Cells as a Source of Engraftable Hepatocyte-Like Cells Using Stem Cell Technology.

PubMed

Sauer, Vanessa; Tchaikovskaya, Tatyana; Wang, Xia; Li, Yanfeng; Zhang, Wei; Tar, Krisztina; Polgar, Zsuzsanna; Ding, Jianqiang; Guha, Chandan; Fox, Ira J; Roy-Chowdhury, Namita; Roy-Chowdhury, Jayanta

2016-12-13

Although several types of somatic cells have been reprogrammed into induced pluripotent stem cells (iPSCs) and then differentiated to hepatocyte-like cells (iHeps), the method for generating such cells from renal tubular epithelial cells shed in human urine and transplanting them into animal livers has not been described systematically. We report reprogramming of human urinary epithelial cells into iPSCs and subsequent hepatic differentiation, followed by a detailed characterization of the newly generated iHeps. The epithelial cells were reprogrammed into iPSCs by delivering the pluripotency factors OCT3/4, SOX2, KLF4, and MYC using methods that do not involve transgene integration, such as nucleofection of episomal (oriP/EBNA-1) plasmids or infection with recombinant Sendai viruses. After characterization of stable iPSC lines, a three-step differentiation toward hepatocytes was performed. The iHeps expressed a large number of hepatocyte-preferred genes, including nuclear receptors that regulate genes involved in cholesterol homeostasis, bile acid transport, and detoxification. MicroRNA profile of the iHeps largely paralleled that of primary human hepatocytes. The iHeps engrafted into the livers of Scid mice transgenic for mutant human SERPINA1 after intrasplenic injection. Thus, urine is a readily available source for generating human iHeps that could be potentially useful for disease modeling, pharmacological development, and regenerative medicine.

A direct assessment of human prion adhered to steel wire using real-time quaking-induced conversion

PubMed Central

Mori, Tsuyoshi; Atarashi, Ryuichiro; Furukawa, Kana; Takatsuki, Hanae; Satoh, Katsuya; Sano, Kazunori; Nakagaki, Takehiro; Ishibashi, Daisuke; Ichimiya, Kazuko; Hamada, Masahisa; Nakayama, Takehisa; Nishida, Noriyuki

2016-01-01

Accidental transmission of prions during neurosurgery has been reported as a consequence of re-using contaminated surgical instruments. Several decontamination methods have been studied using the 263K-hamster prion; however, no studies have directly evaluated human prions. A newly developed in vitro amplification system, designated real-time quaking-induced conversion (RT-QuIC), has allowed the activity of abnormal prion proteins to be assessed within a few days. RT-QuIC using human recombinant prion protein (PrP) showed high sensitivity for prions as the detection limit of our assay was estimated as 0.12 fg of active prions. We applied this method to detect human prion activity on stainless steel wire. When we put wires contaminated with human Creutzfeldt–Jakob disease brain tissue directly into the test tube, typical PrP-amyloid formation was observed within 48 hours, and we could detect the activity of prions at 50% seeding dose on the wire from 102.8 to 105.8 SD50. Using this method, we also confirmed that the seeding activities on the wire were removed following treatment with NaOH. As seeding activity closely correlated with the infectivity of prions using the bioassay, this wire-QuIC assay will be useful for the direct evaluation of decontamination methods for human prions. PMID:27112110

A multi-method approach to curriculum development for in-service training in China's newly established health emergency response offices.

PubMed

Wang, Yadong; Li, Xiangrui; Yuan, Yiwen; Patel, Mahomed S

2014-01-01

To describe an innovative approach for developing and implementing an in-service curriculum in China for staff of the newly established health emergency response offices (HEROs), and that is generalisable to other settings. The multi-method training needs assessment included reviews of the competency domains needed to implement the International Health Regulations (2005) as well as China's policies and emergency regulations. The review, iterative interviews and workshops with experts in government, academia, the military, and with HERO staff were reviewed critically by an expert technical advisory panel. Over 1600 participants contributed to curriculum development. Of the 18 competency domains identified as essential for HERO staff, nine were developed into priority in-service training modules to be conducted over 2.5 weeks. Experts from academia and experienced practitioners prepared and delivered each module through lectures followed by interactive problem-solving exercises and desktop simulations to help trainees apply, experiment with, and consolidate newly acquired knowledge and skills. This study adds to the emerging literature on China's enduring efforts to strengthen its emergency response capabilities since the outbreak of SARS in 2003. The multi-method approach to curriculum development in partnership with senior policy-makers, researchers, and experienced practitioners can be applied in other settings to ensure training is responsive and customized to local needs, resources and priorities. Ongoing curriculum development should reflect international standards and be coupled with the development of appropriate performance support systems at the workplace for motivating staff to apply their newly acquired knowledge and skills effectively and creatively.

Human rights conflicts experienced by nurses migrating between developed countries.

PubMed

Palese, Alvisa; Dobrowolska, Beata; Squin, Anna; Lupieri, Giulia; Bulfone, Giampiera; Vecchiato, Sara

2017-11-01

Some developed countries have recently changed their role in the context of international recruitment, becoming donors due to socio-economical and political factors such as recessions. This is also the case in Italy, where there has been a flow of immigrant nurses out of the country that has been documented over the past several years. In a short time, it has become a donor country to other developed European countries, such as the United Kingdom. To advance knowledge in the context of human rights conflicts and ethical implications of the decision-making process of nurses who migrate between developed countries, such as from Italy to the United Kingdom, during times of recession. A case study based on the descriptive phenomenological approach was undertaken in 2014. Participants and research context: A total of 26 Italian newly graduated nurses finding a job in the United Kingdom were interviewed via Skype and telephone. Ethical considerations: The Internal Review Board of the University approved the project. In accordance with the descriptive phenomenological approach undertaken, three main themes emerged: (1) escaping from the feeling of being refused/rejected in order to be desired, (2) perceiving themselves respected, as a person and as a nurse, in a growth project and (3) returning if the country changes its strategy regarding nurses. Ethical implications in the context of human rights, such as autonomy of the decision, social justice and reciprocal obligation, non-maleficence and double effect, have been discussed. The call for investing in nurses and nurses' care in developed countries facing recession is urgent. Investing in nurses means respecting individuals and citizens who are at risk of developing health problems during the recession.

An empirical examination of the factor structure of compassion.

PubMed

Gu, Jenny; Cavanagh, Kate; Baer, Ruth; Strauss, Clara

2017-01-01

Compassion has long been regarded as a core part of our humanity by contemplative traditions, and in recent years, it has received growing research interest. Following a recent review of existing conceptualisations, compassion has been defined as consisting of the following five elements: 1) recognising suffering, 2) understanding the universality of suffering in human experience, 3) feeling moved by the person suffering and emotionally connecting with their distress, 4) tolerating uncomfortable feelings aroused (e.g., fear, distress) so that we remain open to and accepting of the person suffering, and 5) acting or being motivated to act to alleviate suffering. As a prerequisite to developing a high quality compassion measure and furthering research in this field, the current study empirically investigated the factor structure of the five-element definition using a combination of existing and newly generated self-report items. This study consisted of three stages: a systematic consultation with experts to review items from existing self-report measures of compassion and generate additional items (Stage 1), exploratory factor analysis of items gathered from Stage 1 to identify the underlying structure of compassion (Stage 2), and confirmatory factor analysis to validate the identified factor structure (Stage 3). Findings showed preliminary empirical support for a five-factor structure of compassion consistent with the five-element definition. However, findings indicated that the 'tolerating' factor may be problematic and not a core aspect of compassion. This possibility requires further empirical testing. Limitations with items from included measures lead us to recommend against using these items collectively to assess compassion. Instead, we call for the development of a new self-report measure of compassion, using the five-element definition to guide item generation. We recommend including newly generated 'tolerating' items in the initial item pool, to determine whether or not factor-level issues are resolved once item-level issues are addressed.

Electronic Nose Functionality for Breath Gas Analysis during Parabolic Flight

NASA Astrophysics Data System (ADS)

Dolch, Michael E.; Hummel, Thomas; Fetter, Viktor; Helwig, Andreas; Lenic, Joachim; Moukhamedieva, Lana; Tsarkow, Dimitrij; Chouker, Alexander; Schelling, Gustav

2017-06-01

The presence of humans in space represents a constant threat for their health and safety. Environmental factors such as living in a closed confinement, as well as exposure to microgravity and radiation, are associated with significant changes in bone metabolism, muscular atrophy, and altered immune response, which has impacts on human performance and possibly results in severe illness. Thus, maintaining and monitoring of crew health status has the highest priority to ensure whole mission success. With manned deep space missions to moon or mars appearing at the horizon where short-term repatriation back to earth is impossible the availability of appropriate diagnostic platforms for crew health status is urgently needed. In response to this need, the present experiment evaluated the functionality and practicability of a metal oxide based sensor system (eNose) together with a newly developed breath gas collecting device under the condition of altering acceleration. Parabolic flights were performed with an Airbus A300 ZeroG at Bordeaux, France. Ambient air and exhaled breath of five healthy volunteers was analyzed during steady state flight and parabolic flight maneuvres. All volunteers completed the study, the breath gas collecting device valves worked appropriately, and breathing through the collecting device was easy and did not induce discomfort. During breath gas measurements, significant changes in metal oxide sensors, mainly sensitive to aromatic and sulphur containing compounds, were observed with alternating conditions of acceleration. Similarly, metal oxide sensors showed significant changes in all sensors during ambient air measurements. The eNose as well as the newly developed breath gas collecting device, showed appropriate functionality and practicability during alternating conditions of acceleration which is a prerequisite for the intended use of the eNose aboard the International Space Station (ISS) for breath gas analysis and crew health status monitoring. The observed changes in breath gas composition are most likely associated with changes in ambient air volatile organic and inorganic compound composition and require further evaluation.

Non-animal methods to predict skin sensitization (I): the Cosmetics Europe database.

PubMed

Hoffmann, Sebastian; Kleinstreuer, Nicole; Alépée, Nathalie; Allen, David; Api, Anne Marie; Ashikaga, Takao; Clouet, Elodie; Cluzel, Magalie; Desprez, Bertrand; Gellatly, Nichola; Goebel, Carsten; Kern, Petra S; Klaric, Martina; Kühnl, Jochen; Lalko, Jon F; Martinozzi-Teissier, Silvia; Mewes, Karsten; Miyazawa, Masaaki; Parakhia, Rahul; van Vliet, Erwin; Zang, Qingda; Petersohn, Dirk

2018-05-01

Cosmetics Europe, the European Trade Association for the cosmetics and personal care industry, is conducting a multi-phase program to develop regulatory accepted, animal-free testing strategies enabling the cosmetics industry to conduct safety assessments. Based on a systematic evaluation of test methods for skin sensitization, five non-animal test methods (DPRA (Direct Peptide Reactivity Assay), KeratinoSens TM , h-CLAT (human cell line activation test), U-SENS TM , SENS-IS) were selected for inclusion in a comprehensive database of 128 substances. Existing data were compiled and completed with newly generated data, the latter amounting to one-third of all data. The database was complemented with human and local lymph node assay (LLNA) reference data, physicochemical properties and use categories, and thoroughly curated. Focused on the availability of human data, the substance selection resulted nevertheless resulted in a high diversity of chemistries in terms of physico-chemical property ranges and use categories. Predictivities of skin sensitization potential and potency, where applicable, were calculated for the LLNA as compared to human data and for the individual test methods compared to both human and LLNA reference data. In addition, various aspects of applicability of the test methods were analyzed. Due to its high level of curation, comprehensiveness, and completeness, we propose our database as a point of reference for the evaluation and development of testing strategies, as done for example in the associated work of Kleinstreuer et al. We encourage the community to use it to meet the challenge of conducting skin sensitization safety assessment without generating new animal data.

How Can Online Discussion Support and Develop Newly Qualified Teachers? Research Briefing No. 51

ERIC Educational Resources Information Center

Unwin, Adam

2013-01-01

This research investigated newly qualified teachers (NQTs) experiences of participating in online discussions (ODs) that were part of their Master of Teaching (MTeach) course. [The project was partially funded by the Excellence in Work-Based Learning for Education Professionals (WLE) Centre in 2009.

Quantification of the fate of dietary fiber in humans by a newly developed radiolabeled fiber marker.

PubMed

Carryer, P W; Brown, M I; Malagelada, J R; Carlson, G L; McCall, J T

1982-06-01

A radiolabeled cellulose (131I-fiber) that retains the essential physical and chemical properties of this class of fiber was developed in our laboratory. We quantified the fate of orally ingested 131I-fiber in healthy individuals by external gamma camera monitoring and fecal collections. The marker passes virtually intact through the human gastrointestinal tract with negligible release and absorption of the label in the gut. Comparison of the gastric emptying rate of 131I-fiber with that of a predominantly aqueous marker, 99mTc-diethylenetriamine pentaacetic acid (99mTc-DTPA), showed that 131I-fiber strands were evacuated more slowly than intragastric fluids. An important finding was that some 131I-fiber emptying occurred during most time periods, even before liquids were completely evacuated. This suggests that the human stomach is able to empty simultaneously liquids and fiber strands (1-15 mm in length) that are resistant to grinding by antral mechanical forces and to digestion by acid-peptic secretion. Thus, some nondigestible solids may be emptied with the bulk of a meal, although at a slower rate. 131I-Fiber may be a useful marker for quantifying gastric emptying of nondigestible solids. Further, the stability of 131I-fiber in the gut, as opposed to most other physiologic solid labels, should enable future investigation of intestinal and colonic transit of fiber, which is an important component of the human diet.

Development of an interleukin (IL)-33 sandwich ELISA kit specific for mature IL-33.

PubMed

Kim, Eunsom; Kwak, Areum; Jhun, Hyunjhung; Lee, Siyoung; Jo, Seunghyun; Lee, Jongho; Kang, Tae-Bong; Her, Erk; Bae, Suyoung; Lee, Youngmin; Kim, Soohyun

2016-01-01

Interleukin (IL)-33 is an inflammatory cytokine and belongs to the IL-1 family of cytokines. There are eleven members of the IL-1 family of cytokines and all have important roles in host defense against infections. Their levels are increased during infection and in various auto-inflammatory diseases. IL-33 is also associated with autoimmune diseases such as asthma, atopic dermatitis, rheumatoid arthritis, and atherosclerosis. IL-33 receptors consist of IL-1R4 and IL-1R3 to induce both Th1 and Th2 type immune response. Here we present the development of monoclonal antibodies (mAbs) against human mature IL-33. Recombinant human mature IL-33 protein was expressed in E. coli and purified by multi-step affinity chromatography. The human IL-33 activity was examined in HMC-1 and Raw 264.7 cells. Mice were immunized with the biologically active mature IL-33 to generate mAb against IL-33. The anti-IL-33 mAb (clone/4) was used as a capture antibody for a sandwich enzyme-linked immunosorbent assay (ELISA). This assay detects mature IL-33 with a high sensitivity (80 pg/mL) but does not recognize the biologically inactive precursor IL-33. This article describes the methods for a newly developed IL-33 ELISA kit that is specific for mature IL-33 and may be used to analyze bioactive mature IL-33 in various immunological diseases.

Heterologous expression of Homo sapiens alpha-folate receptors in E. coli by fusion with a trigger factor for enhanced solubilization.

PubMed

Miranda, Beatriz Nogueira Messias; Fotoran, Wesley Luzetti; Canduri, Fernanda; Souza, Dulce Helena Ferreira; Wunderlich, Gerhard; Carrilho, Emanuel

2018-02-01

The role of Alpha folate receptors (FRα) in folate metabolism and cancer development has been extensively studied. The reason for this is not only associated to its direct relation to disease development but also to its potential use as a highly sensitive and specific biomarker for cancers therapies. Over the recent years, the crystal structures of human FRα complexed with different ligands were described relying on an expensive and time-consuming production process. Here, we constructed an efficient system for the expression and purification of a human FRα in E. coli. Unlike a conventional expression method we used a specific protein fusion expressing the target protein together with a trigger factor (TF). This factor is a chaperone from E. coli that assists the correct folding of newly synthesized polypeptide chains. The activity of rTFFRα was comparable to glycosylphosphatidylinositol (GPI) anchored proteins extracted from HeLa tumor cells. Our work demonstrates a straightforward and versatile approach for the production of active human FRα by heterologous expression; this approach further enhances the development of inhibition studies and biotechnological applications. The purified product was then conjugated to liposomes, obtaining a 35% higher signal from densitometry measurement on the immunoblotting assay in the contruct containing the Ni-NTA tag, as a mimesis of an exosome, which is of vital importance to nanotherapeutic techniques associated to treatment and diagnosis of tumors. Copyright © 2017 Elsevier Inc. All rights reserved.

Balkan Endemic Nephropathy - Still continuing enigma, risk assessment and underestimated hazard of joint mycotoxin exposure of animals or humans.

PubMed

Stoev, Stoycho D

2017-01-05

The spreading of mycotoxic nephropathy in animals/humans was studied. The possible etiological causes provoking this nephropathy were carefully reviewed and analyzed. The natural content of the most frequent nephrotoxic mycotoxins in target feedstuffs/foods were investigated, in addition to their significance for development of renal damages in endemic areas. An estimation of the level of exposure of humans to the nephrotoxic mycotoxin, ochratoxin A (OTA), is made. The possible synergism or additive effects between some target mycotoxins in the development of nephropathy is also covered. The significance of joint mycotoxin interaction and masked mycotoxins, in addition to some newly isolated fungal toxic agents in the complicated etiology of mycotoxic nephropathy ranged in Balkan countries is discussed. The importance of some target fungal species which can induce kidney damages was evaluated. The morphological/ultrastructural, functional and toxicological similarities between human and animal nephropathy are studied. The possible hazard of low content of combinations of some target mycotoxins in food or feedstuff ingested by pigs, chickens or humans under natural conditions is evaluated and a risk assessment was made. Some different but more effective manners of prophylaxis and/or prevention against OTA contamination of feedstuffs/foods are suggested. A survey was made in regard to the best possible ways of veterinary hygiene control of OTA-exposed animals at slaughter time for preventing the entrance of OTA in commercial feedstuffs/food channels with a view to reduce the possible health hazard for humans. The economic efficacy and applicability of such preventive measures is additionally discussed and some practical suggestions are made. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Analysis of the proposed EU regulation concerning biocide products and its opportunities for alternative approaches and a toxicology for the 21st century (t4 report).

PubMed

Ferrario, Daniele; Rabbit, Richard R

2012-01-01

On June 12, 2009, the European Commission adopted a proposal for a Regulation concerning the placement on the market and use of biocidal products, which, when it enters into force on January 1, 2013, will repeal and replace Directive 98/8/EC. The main reason for the revision of the current Directive was to promote best practices for environmental and human health protection, along with implementation of current developments in safety testing in order to create safer biocides. Moreover, the proposed Regulation aims to take into consideration the newest legislation on chemicals. This article evaluates the proposed Regulation in comparison to Directive 98/8/EC. Although the new proposal requires the sharing of vertebrate animal test data, both for product authorization and for newly developed active substances, it misses - in contrast to REACH - the opportunity to recognize the accelerating development of alternative approaches to animal testing, most recently with new momentum provided by "Toxicity Testing for the 21st Century", and to support the evolution of toxicology towards a new approach to testing. The new methods promise not only to decrease animal pain and suffering, but also to provide faster results and better prediction for human risk assessment compared to traditional methods. Unfortunately, methods mandated for human risk assessment in the proposal are still mainly based on traditional animal study extrapolation. We put forward and discuss possible alternative strategies, such as in vitro testing, integrated testing strategies, toxicokinetics, "omics", systems biology, bioinformatics, and computational modeling, all of which could be more encouraged by the proposal. Current opportunities to improve our tools for biocide risk assessment are discussed, delineating advantages, limitations, and development needs. It is suggested to open the proposed Regulation to alternative approaches that are based on human biology more than on extrapolation from animals to humans.

Handbook to Support the Installation Restoration Program (IRP) statements of Work. Volume 1. Remedial Investigation/Feasibility Studies (RI/FS)

DTIC Science & Technology

1991-05-01

FEASIBILITY STUDIES (RI/FS) ENVIRONMENTAL RESTORATION DIV STAFF MAY 1991 (REPRINT) - Distribution is unlimited; approved for public release ENVIRONMENTAL ...RESTORATION DIVISION (ESR) ENVIRONMENTAL SERVICES OFFICE AIR FORCE CENTER FOR ENVIRONMENTAL EXCELLENCE (AFCEE) BROOKS AIR FORCE BASE, TEXAS S(4 93-05296...Human Systems Division’s Human Systems Program Office, IRP Divisicn (HSD/YAQ) was transferred to the newly formed Air Force Center for Environmental

Morphological studies of the developing human esophageal epithelium.

PubMed

Ménard, D

1995-06-15

This article focusses on the structural development of human esophageal ciliated epithelium. A combination of transmission electron microscopic (TEM), scanning electron microscopic (SEM), radioautographic, and light microscopic (LM) analyses were carried out using intact fetal tissues between 8 and 20 weeks of gestation as well as cultured esophageal explants. Up to the age of 10 weeks, the stratified esophageal epithelium consisted of two longitudinal primary folds. The surface cells were undifferentiated and contained large glycogen aggregates. Between 11 and 16 weeks, the primary folds (now up to four) had developed secondary folds. The thickness of the epithelium drastically increased (123%) in concomittance with a differentiation of surface columnar ciliated cells. These highly specialized surface cells exhibited junctional complexes and well-developed organelles with numerous microvilli interspersed among the cilia. Transverse sections revealed the internal structure of the cilia with a consistent pattern of nine doublet microtubules surrounding a central pair of single microtubules. Freeze-fracture studies illustrated the presence of a ciliary necklace composed of 6 ring-like rows of intramembranous particles. They also revealed the structure of ciliary cell tight junctions consisting of up to nine anastomosing strands (P-face) or complementary grooves (E-face). Ultrastructural studies (LM, TEM, SEM) of the esophageal squamous epithelium obtained after 15 days of culture showed that the newly formed epithelium was similar to adult human epithelium. Finally LM and SEM observations established that the esophagogastric junction was not yet well delineated, consisting of a transitional area composed of a mixture of esophageal ciliated cells and gastric columnar mucous cells.

Vaccine platform recombinant measles virus.

PubMed

Mühlebach, Michael D

2017-10-01

The classic development of vaccines is lengthy, tedious, and may not necessarily be successful as demonstrated by the case of HIV. This is especially a problem for emerging pathogens that are newly introduced into the human population and carry the inherent risk of pandemic spread in a naïve population. For such situations, a considerable number of different platform technologies are under development. These are also under development for pathogens, where directly derived vaccines are regarded as too complicated or even dangerous due to the induction of inefficient or unwanted immune responses causing considerable side-effects as for dengue virus. Among platform technologies are plasmid-based DNA vaccines, RNA replicons, single-round infectious vector particles, or replicating vaccine-based vectors encoding (a) critical antigen(s) of the target pathogens. Among the latter, recombinant measles viruses derived from vaccine strains have been tested. Measles vaccines are among the most effective and safest life-attenuated vaccines known. Therefore, the development of Schwarz-, Moraten-, or AIK-C-strain derived recombinant vaccines against a wide range of mostly viral, but also bacterial pathogens was quite straightforward. These vaccines generally induce powerful humoral and cellular immune responses in appropriate animal models, i.e., transgenic mice or non-human primates. Also in the recent first clinical phase I trial, the results have been quite encouraging. The trial indicated the expected safety and efficacy also in human patients, interestingly independent from the level of prevalent anti-measles immunity before the trial. Thereby, recombinant measles vaccines expressing additional antigens are a promising platform for future vaccines.

The curiously suspicious: a role for Epstein-Barr virus in lupus.

PubMed

Harley, J B; Harley, I T W; Guthridge, J M; James, J A

2006-01-01

While the events initiating the development of autoantibodies in systemic lupus erythematosus (SLE) have not yet been convincingly established, newly developed tools for molecular investigation make such an undertaking increasingly practical. Applied to the earliest events in the sequence culminating in lupus autoimmunity, we present a critical potential role for Epstein-Barr virus (EBV) in the development and perhaps perpetuation of SLE. The expected properties for an environmental risk factor for SLE are found in this virus and the human host response against it. Existing data show the molecular progression to autoimmunity observed in SLE patient sera, the discovery of the first autoimmune epitopes in the Sm and Ro autoantigen systems, and the possible emergence of these autoantibodies from the heterologous antibodies against Epstein-Barr nuclear antigen-1 (EBNA-1). Further, existing data demonstrate association of SLE with EBV infection, even preceding the development of autoimmunity. Finally, the data are consistent with a proposed model of lupus pathogenesis that begins with antibodies to EBNA-1, predisposing to immune responses that develop crossreactive autoantibodies that culminate in the development of SLE autoimmunity.

Automated selection of trabecular bone regions in knee radiographs.

PubMed

Podsiadlo, P; Wolski, M; Stachowiak, G W

2008-05-01

Osteoarthritic (OA) changes in knee joints can be assessed by analyzing the structure of trabecular bone (TB) in the tibia. This analysis is performed on TB regions selected manually by a human operator on x-ray images. Manual selection is time-consuming, tedious, and expensive. Even if a radiologist expert or highly trained person is available to select regions, high inter- and intraobserver variabilities are still possible. A fully automated image segmentation method was, therefore, developed to select the bone regions for numerical analyses of changes in bone structures. The newly developed method consists of image preprocessing, delineation of cortical bone plates (active shape model), and location of regions of interest (ROI). The method was trained on an independent set of 40 x-ray images. Automatically selected regions were compared to the "gold standard" that contains ROIs selected manually by a radiologist expert on 132 x-ray images. All images were acquired from subjects locked in a standardized standing position using a radiography rig. The size of each ROI is 12.8 x 12.8 mm. The automated method results showed a good agreement with the gold standard [similarity index (SI) = 0.83 (medial) and 0.81 (lateral) and the offset =[-1.78, 1.27]x[-0.65,0.26] mm (medial) and [-2.15, 1.59]x[-0.58, 0.52] mm (lateral)]. Bland and Altman plots were constructed for fractal signatures, and changes of fractal dimensions (FD) to region offsets calculated between the gold standard and automatically selected regions were calculated. The plots showed a random scatter and the 95% confidence intervals were (-0.006, 0.008) and (-0.001, 0.011). The changes of FDs to region offsets were less than 0.035. Previous studies showed that differences in FDs between non-OA and OA bone regions were greater than 0.05. ROIs were also selected by a second radiologist and then evaluated. Results indicated that the newly developed method could replace a human operator and produces bone regions with an accuracy that is sufficient for fractal analyses of bone texture.

Reinforcing the role of the conventional C-arm - a novel method for simplified distal interlocking

PubMed Central

2012-01-01

Background The common practice for insertion of distal locking screws of intramedullary nails is a freehand technique under fluoroscopic control. The process is technically demanding, time-consuming and afflicted to considerable radiation exposure of the patient and the surgical personnel. A new concept is introduced utilizing information from within conventional radiographic images to help accurately guide the surgeon to place the interlocking bolt into the interlocking hole. The newly developed technique was compared to conventional freehand in an operating room (OR) like setting on human cadaveric lower legs in terms of operating time and radiation exposure. Methods The proposed concept (guided freehand), generally based on the freehand gold standard, additionally guides the surgeon by means of visible landmarks projected into the C-arm image. A computer program plans the correct drilling trajectory by processing the lens-shaped hole projections of the interlocking holes from a single image. Holes can be drilled by visually aligning the drill to the planned trajectory. Besides a conventional C-arm, no additional tracking or navigation equipment is required. Ten fresh frozen human below-knee specimens were instrumented with an Expert Tibial Nail (Synthes GmbH, Switzerland). The implants were distally locked by performing the newly proposed technique as well as the conventional freehand technique on each specimen. An orthopedic resident surgeon inserted four distal screws per procedure. Operating time, number of images and radiation time were recorded and statistically compared between interlocking techniques using non-parametric tests. Results A 58% reduction in number of taken images per screw was found for the guided freehand technique (7.4 ± 3.4) (mean ± SD) compared to the freehand technique (17.6 ± 10.3) (p < 0.001). Total radiation time (all 4 screws) was 55% lower for the guided freehand technique compared to conventional freehand (p = 0.001). Operating time per screw (from first shot to screw tightened) was on average 22% reduced by guided freehand (p = 0.018). Conclusions In an experimental setting, the newly developed guided freehand technique for distal interlocking has proven to markedly reduce radiation exposure when compared to the conventional freehand technique. The method utilizes established clinical workflows and does not require cost intensive add-on devices or extensive training. The underlying principle carries potential to assist implant positioning in numerous other applications within orthopedics and trauma from screw insertions to placement of plates, nails or prostheses. PMID:22276698

A graphical simulation software for instruction in cardiovascular mechanics physiology.

PubMed

Wildhaber, Reto A; Verrey, François; Wenger, Roland H

2011-01-25

Computer supported, interactive e-learning systems are widely used in the teaching of physiology. However, the currently available complimentary software tools in the field of the physiology of cardiovascular mechanics have not yet been adapted to the latest systems software. Therefore, a simple-to-use replacement for undergraduate and graduate students' education was needed, including an up-to-date graphical software that is validated and field-tested. Software compatible to Windows, based on modified versions of existing mathematical algorithms, has been newly developed. Testing was performed during a full term of physiological lecturing to medical and biology students. The newly developed CLabUZH software models a reduced human cardiovascular loop containing all basic compartments: an isolated heart including an artificial electrical stimulator, main vessels and the peripheral resistive components. Students can alter several physiological parameters interactively. The resulting output variables are printed in x-y diagrams and in addition shown in an animated, graphical model. CLabUZH offers insight into the relations of volume, pressure and time dependency in the circulation and their correlation to the electrocardiogram (ECG). Established mechanisms such as the Frank-Starling Law or the Windkessel Effect are considered in this model. The CLabUZH software is self-contained with no extra installation required and runs on most of today's personal computer systems. CLabUZH is a user-friendly interactive computer programme that has proved to be useful in teaching the basic physiological principles of heart mechanics.

Newly developed liquid-based cytology. TACAS™: cytological appearance and HPV testing using liquid-based sample.

PubMed

Kubushiro, Kaneyuki; Taoka, Hideki; Sakurai, Nobuyuki; Yamamoto, Yasuhiro; Kurasaki, Akiko; Asakawa, Yasuyuki; Iwahara, Minoru; Takahashi, Kei

2011-09-01

Cell profiles determined by the thin-layer advanced cytology assay system (TACAS™), a liquid-based cytology technique newly developed in Japan, were analyzed in this study. Hybrid capture 2 (HC-2) was also performed using the liquid-based samples prepared by TACAS to ascertain its ability to detect human papillomavirus (HPV). Cell collection samples from uterine cervix were obtained from 359 patients and examined cytologically. A HC-2 assay for HPV was carried out in the cell specimens. All specimens were found to show background factors such as leukocytes. After excluding the 5 unsatisfactory cases from the total 354 cases, 82 cases (23.2%) were positive and 272 cases (76.8%) were negative for HPV. Cell specimens from 30 HPV-positive cases and 166 HPV-negative cases were subjected to 4 weeks of preservation at room temperature. Then, when subsequently re-assayed, 28 cases (93.3%) in the former group were found to be HPV positive and 164 cases (98.8%) in the latter group were found to be HPV negative. These results supported the excellent reproducibility of TACAS for HPV testing. A reasonable inference from the foregoing analysis is that TACAS may be distinguished from other liquid-based cytological approaches, such as ThinPrep and SurePath, in that it can retain the cell backgrounds. Furthermore, this study raises the possibility that cell specimens prepared using TACAS could be preserved for at least 4 weeks prior to carrying out a HC-2 assay for HPV.

Human face detection using motion and color information

NASA Astrophysics Data System (ADS)

Kim, Yang-Gyun; Bang, Man-Won; Park, Soon-Young; Choi, Kyoung-Ho; Hwang, Jeong-Hyun

2008-02-01

In this paper, we present a hardware implementation of a face detector for surveillance applications. To come up with a computationally cheap and fast algorithm with minimal memory requirement, motion and skin color information are fused successfully. More specifically, a newly appeared object is extracted first by comparing average Hue and Saturation values of background image and a current image. Then, the result of skin color filtering of the current image is combined with the result of a newly appeared object. Finally, labeling is performed to locate a true face region. The proposed system is implemented on Altera Cyclone2 using Quartus II 6.1 and ModelSim 6.1. For hardware description language (HDL), Verilog-HDL is used.

Positive and negative sources of emotional arousal enhance long-term word-list retention when induced as long as 30 min after learning.

PubMed

Nielson, Kristy A; Powless, Mark

2007-07-01

The consolidation of newly formed memories occurs slowly, allowing memories to be altered by experience for some time after their formation. Various treatments, including arousal, can modulate memory consolidation when given soon after learning, but the degree of time-dependency of these treatments in humans has not been studied. Thus, 212 participants learned a word list, which was followed by either a positively or negatively valenced arousing video clip (i.e., comedy or surgery, respectively) after delays of 0, 10, 30 or 45 min. Arousal of either valence induced up to 30 min after learning, but not after 45 min, significantly enhanced one-week retrieval. The findings support (1) the time-dependency of memory modulation in humans and (2) other studies that suggest that it is the degree of arousal, rather than valence that modulates memory. Important implications for developing memory intervention strategies and for preserving and validating witness testimony are discussed.

Characterization of gloss properties of differently treated polymer coating surfaces by surface clarity measurement methodology.

PubMed

Gruber, Dieter P; Buder-Stroisznigg, Michael; Wallner, Gernot; Strauß, Bernhard; Jandel, Lothar; Lang, Reinhold W

2012-07-10

With one measurement configuration, existing gloss measurement methodologies are generally restricted to specific gloss levels. A newly developed image-analytical gloss parameter called "clarity" provides the possibility to describe the perceptual result of a broad range of different gloss levels with one setup. In order to analyze and finally monitor the perceived gloss of products, a fast and flexible method also for the automated inspection is highly demanded. The clarity parameter is very fast to calculate and therefore usable for fast in-line surface inspection. Coated metal specimens were deformed by varying degree and polished afterwards in order to study the clarity parameter regarding the quantification of varying surface gloss types and levels. In order to analyze the correlation with the human gloss perception a study was carried out in which experts were asked to assess gloss properties of a series of surface samples under standardized conditions. The study confirmed clarity to exhibit considerably better correlation to the human perception than alternative gloss parameters.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gardner, Shea N.; McLoughlin, Kevin; Be, Nicholas A.

Venezuelan equine encephalitis virus (VEEV) is a mosquito-borne alphavirus that has caused large outbreaks of severe illness in both horses and humans. New approaches are needed to rapidly infer the origin of a newly discovered VEEV strain, estimate its equine amplification and resultant epidemic potential, and predict human virulence phenotype. We performed whole genome single nucleotide polymorphism (SNP) analysis of all available VEE antigenic complex genomes, verified that a SNP-based phylogeny accurately captured the features of a phylogenetic tree based on multiple sequence alignment, and developed a high resolution genome-wide SNP microarray. We used the microarray to analyze a broadmore » panel of VEEV isolates, found excellent concordance between array- and sequence-based SNP calls, genotyped unsequenced isolates, and placed them on a phylogeny with sequenced genomes. The microarray successfully genotyped VEEV directly from tissue samples of an infected mouse, bypassing the need for viral isolation, culture and genomic sequencing. Lastly, we identified genomic variants associated with serotypes and host species, revealing a complex relationship between genotype and phenotype.« less

Accurate and sensitive quantification of protein-DNA binding affinity.

PubMed

Rastogi, Chaitanya; Rube, H Tomas; Kribelbauer, Judith F; Crocker, Justin; Loker, Ryan E; Martini, Gabriella D; Laptenko, Oleg; Freed-Pastor, William A; Prives, Carol; Stern, David L; Mann, Richard S; Bussemaker, Harmen J

2018-04-17

Transcription factors (TFs) control gene expression by binding to genomic DNA in a sequence-specific manner. Mutations in TF binding sites are increasingly found to be associated with human disease, yet we currently lack robust methods to predict these sites. Here, we developed a versatile maximum likelihood framework named No Read Left Behind (NRLB) that infers a biophysical model of protein-DNA recognition across the full affinity range from a library of in vitro selected DNA binding sites. NRLB predicts human Max homodimer binding in near-perfect agreement with existing low-throughput measurements. It can capture the specificity of the p53 tetramer and distinguish multiple binding modes within a single sample. Additionally, we confirm that newly identified low-affinity enhancer binding sites are functional in vivo, and that their contribution to gene expression matches their predicted affinity. Our results establish a powerful paradigm for identifying protein binding sites and interpreting gene regulatory sequences in eukaryotic genomes. Copyright © 2018 the Author(s). Published by PNAS.

Accurate and sensitive quantification of protein-DNA binding affinity

PubMed Central

Rastogi, Chaitanya; Rube, H. Tomas; Kribelbauer, Judith F.; Crocker, Justin; Loker, Ryan E.; Martini, Gabriella D.; Laptenko, Oleg; Freed-Pastor, William A.; Prives, Carol; Stern, David L.; Mann, Richard S.; Bussemaker, Harmen J.

2018-01-01

Transcription factors (TFs) control gene expression by binding to genomic DNA in a sequence-specific manner. Mutations in TF binding sites are increasingly found to be associated with human disease, yet we currently lack robust methods to predict these sites. Here, we developed a versatile maximum likelihood framework named No Read Left Behind (NRLB) that infers a biophysical model of protein-DNA recognition across the full affinity range from a library of in vitro selected DNA binding sites. NRLB predicts human Max homodimer binding in near-perfect agreement with existing low-throughput measurements. It can capture the specificity of the p53 tetramer and distinguish multiple binding modes within a single sample. Additionally, we confirm that newly identified low-affinity enhancer binding sites are functional in vivo, and that their contribution to gene expression matches their predicted affinity. Our results establish a powerful paradigm for identifying protein binding sites and interpreting gene regulatory sequences in eukaryotic genomes. PMID:29610332

A mathematical model of transport and regional uptake of radioactive gases in the human respiratory system

NASA Astrophysics Data System (ADS)

Baek, Inseok

The purpose of this research is to describe the development of a mathematical model of diffusion, convection, and lateral transport into the airway wall and alveolar absorption for inhaled radioactive gases in the human conductive and respiratory airways based on a Single Path Trumpet-bell model (SPM). Mathematical simulation models have been used successfully to study transport, absorption into the blood through alveoli, and lung tissue uptake of soluble and nonreactive radioactive gases. Results from such simulations also show clearly that inhaled radioactive gases are absorbed into the lung tissues as well as into the blood through the alveoli. In contrast to previous reports in the literature, the present study found that blood uptake through alveoli is much greater than that calculated previously. Regional depositions in the lung from inhaled radioactive gases are presented as the result of this simulation. The committed effective dose to lung tissue due to submersion in radioactive clouds has been newly defined using the results of this simulation.

The effect of Bacopa monnieri on gene expression levels in SH-SY5Y human neuroblastoma cells.

PubMed

Leung, How-Wing; Foo, Gabriel; Banumurthy, Gokulakrishna; Chai, Xiaoran; Ghosh, Sujoy; Mitra-Ganguli, Tora; VanDongen, Antonius M J

2017-01-01

Bacopa monnieri is a plant used as a nootropic in Ayurveda, a 5000-year-old system of traditional Indian medicine. Although both animal and clinical studies supported its role as a memory enhancer, the molecular and cellular mechanism underlying Bacopa's nootropic action are not understood. In this study, we used deep sequencing (RNA-Seq) to identify the transcriptome changes upon Bacopa treatment on SH-SY5Y human neuroblastoma cells. We identified several genes whose expression levels were regulated by Bacopa. Biostatistical analysis of the RNA-Seq data identified biological pathways and molecular functions that were regulated by Bacopa, including regulation of mRNA translation and transmembrane transport, responses to oxidative stress and protein misfolding. Pathway analysis using the Ingenuity platform suggested that Bacopa may protect against brain damage and improve brain development. These newly identified molecular and cellular determinants may contribute to the nootropic action of Bacopa and open up a new direction of investigation into its mechanism of action.

The effect of Bacopa monnieri on gene expression levels in SH-SY5Y human neuroblastoma cells

PubMed Central

Foo, Gabriel; Banumurthy, Gokulakrishna; Chai, Xiaoran; Ghosh, Sujoy

2017-01-01

Bacopa monnieri is a plant used as a nootropic in Ayurveda, a 5000-year-old system of traditional Indian medicine. Although both animal and clinical studies supported its role as a memory enhancer, the molecular and cellular mechanism underlying Bacopa’s nootropic action are not understood. In this study, we used deep sequencing (RNA-Seq) to identify the transcriptome changes upon Bacopa treatment on SH-SY5Y human neuroblastoma cells. We identified several genes whose expression levels were regulated by Bacopa. Biostatistical analysis of the RNA-Seq data identified biological pathways and molecular functions that were regulated by Bacopa, including regulation of mRNA translation and transmembrane transport, responses to oxidative stress and protein misfolding. Pathway analysis using the Ingenuity platform suggested that Bacopa may protect against brain damage and improve brain development. These newly identified molecular and cellular determinants may contribute to the nootropic action of Bacopa and open up a new direction of investigation into its mechanism of action. PMID:28832626

Characteristic hydrolyzing of megalosaccharide by human salivary α-amylase and small intestinal enzymes, and its bioavailability in healthy subjects.

PubMed

Nakamura, Sadako; Takami, Masayuki; Tanabe, Kenichi; Oku, Tsuneyuki

2014-09-01

The digestibility of Megalosaccharide® (newly developed carbohydrate comprising α-1,4-glucosaccharide) was investigated in vitro and in vivo. Isomaltosyl-megalosaccharide® (IMS) and nigerosyl-megalosaccharide® (NMS) contain 20% and 50% of the megalosaccharide fraction (degree of polymerization (DP) 10-35), respectively. IMS was hydrolyzed readily by α-amylase to oligosaccharides (DP ≤ 7), and a small amount of glucose was produced from oligosaccharides by small intestinal enzymes (SIEs). NMS was partially hydrolyzed by α-amylase to oligosaccharides, and a small amount of glucose produced by SIEs. When IMS and NMS were treated by SIEs after treatment with human saliva α-amylase for a few minutes, IMS and NMS were hydrolyzed readily to glucose. Plasma levels of glucose and insulin upon ingestion of 50 g of IMS or NMS were elevated the same as those for 50 g of glucose, and breath hydrogen was not excreted. These results suggest that IMS and NMS are digestible carbohydrates.

Detection and characterization of Human caliciviruses associated with sporadic acute diarrhea in adults in Djibouti (horn of Africa).

PubMed

Maslin, Jérôme; Nicand, Elisabeth; Ambert-Balay, Katia; Fouet, Christine; Kaplon, Jérôme; Haus, Rachel; Pothier, Pierre; Kohli, Evelyne

2008-03-01

Recent advances in molecular diagnostics have allowed us to recognize Human caliciviruses (HuCVs) as important agents of acute diarrhea in industrialized countries. Their prevalence and genetic diversity in developing countries remains unknown. We report on the characterization of HuCVs among adults presenting acute diarrheas in Djibouti; 108 stool samples collected were screened by EIA, RTPCR, or cell cultures for the group A Rotaviruses, Adenoviruses, Astroviruses, and HuCVs, which were further characterized by genotyping. Among stool samples screened for HuCVs, 25.3% were positive. The other enteric viruses were less prevalent. The 11 HuCV strains sequenced revealed a large diversity (3 sapoviruses and 8 noroviruses). GII strains noroviruses were predominant, five were newly described genotypes, and two were recombinant with a pol gene related to GGIIb strains with the particularity to associate a unique pol gene to different capsid genes. These results could help to the knowledge of HuCV infections in Tropical Africa.

Automated Video-Based Analysis of Contractility and Calcium Flux in Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes Cultured over Different Spatial Scales.

PubMed

Huebsch, Nathaniel; Loskill, Peter; Mandegar, Mohammad A; Marks, Natalie C; Sheehan, Alice S; Ma, Zhen; Mathur, Anurag; Nguyen, Trieu N; Yoo, Jennie C; Judge, Luke M; Spencer, C Ian; Chukka, Anand C; Russell, Caitlin R; So, Po-Lin; Conklin, Bruce R; Healy, Kevin E

2015-05-01

Contractile motion is the simplest metric of cardiomyocyte health in vitro, but unbiased quantification is challenging. We describe a rapid automated method, requiring only standard video microscopy, to analyze the contractility of human-induced pluripotent stem cell-derived cardiomyocytes (iPS-CM). New algorithms for generating and filtering motion vectors combined with a newly developed isogenic iPSC line harboring genetically encoded calcium indicator, GCaMP6f, allow simultaneous user-independent measurement and analysis of the coupling between calcium flux and contractility. The relative performance of these algorithms, in terms of improving signal to noise, was tested. Applying these algorithms allowed analysis of contractility in iPS-CM cultured over multiple spatial scales from single cells to three-dimensional constructs. This open source software was validated with analysis of isoproterenol response in these cells, and can be applied in future studies comparing the drug responsiveness of iPS-CM cultured in different microenvironments in the context of tissue engineering.

Advances in Bacterial Methionine Aminopeptidase Inhibition

PubMed Central

Helgren, Travis R.; Wangtrakuldee, Phumvadee; Staker, Bart L.; Hagen, Timothy J.

2016-01-01

Methionine aminopeptidases (MetAPs) are metalloenzymes that cleave the N-terminal methionine from newly synthesized peptides and proteins. These MetAP enzymes are present in bacteria, and knockout experiments have shown that MetAP activity is essential for cell life, suggesting that MetAPs are good antibacterial drug targets. MetAP enzymes are also present in the human host and selectivity is essential. There have been significant structural biology efforts and over 65 protein crystal structures of bacterial MetAPs are deposited into the PDB. This review highlights the available crystallographic data for bacterial MetAPs. Structural comparison of bacterial MetAPs with human MetAPs highlights differences that can lead to selectivity. In addition, this review includes the chemical diversity of molecules that bind and inhibit the bacterial MetAP enzymes. Analysis of the structural biology and chemical space of known bacterial MetAP inhibitors leads to a greater understanding of this antibacterial target and the likely development of potential antibacterial agents. PMID:26268344

Discovery of Cellular Proteins Required for the Early Steps of HCV Infection Using Integrative Genomics

PubMed Central

Yang, Jae-Seong; Kwon, Oh Sung; Kim, Sanguk; Jang, Sung Key

2013-01-01

Successful viral infection requires intimate communication between virus and host cell, a process that absolutely requires various host proteins. However, current efforts to discover novel host proteins as therapeutic targets for viral infection are difficult. Here, we developed an integrative-genomics approach to predict human genes involved in the early steps of hepatitis C virus (HCV) infection. By integrating HCV and human protein associations, co-expression data, and tight junction-tetraspanin web specific networks, we identified host proteins required for the early steps in HCV infection. Moreover, we validated the roles of newly identified proteins in HCV infection by knocking down their expression using small interfering RNAs. Specifically, a novel host factor CD63 was shown to directly interact with HCV E2 protein. We further demonstrated that an antibody against CD63 blocked HCV infection, indicating that CD63 may serve as a new therapeutic target for HCV-related diseases. The candidate gene list provides a source for identification of new therapeutic targets. PMID:23593195

The manifestation of optical centers in UV-Vis absorption and luminescence spectra of white blood human cells

NASA Astrophysics Data System (ADS)

Terent'yeva, Yu G.; Yashchuk, V. M.; Zaika, L. A.; Snitserova, O. M.; Losytsky, M. Yu

2016-12-01

A white blood human cells spectral investigation is presented. The aim of this series of experiments was to obtain and analyze the absorption and luminescence (fluorescence and phosphorescence) spectra at room temperature and at 78 K of newly isolated white blood human cells and their organelles. As a result the optical centers and possible biochemical components that form the studied spectra where identified. Also the differences between the spectra of abnormal cells (B-cell chronic lymphocytic leukemia BCLL) and normal ones were studied for the whole cells and individual organelles.

Learning beyond Graduation: Exploring Newly Qualified Specialists' Entrance into Daily Practice from a Learning Perspective

ERIC Educational Resources Information Center

Cuyvers, Katrien; Donche, Vincent; Van den Bossche, Piet

2016-01-01

The entrance of newly qualified medical specialists into daily practice is considered to be a stressful period in which curriculum support is absent. Although engaging in both personal and professional learning and development activities is recognized fundamental for lifelong professional competence, research on medical professionals' entrance…

76 FR 78929 - Establishing Timeframes for Implementation of Product Safety Labeling Changes; Request for Comments

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-20

... labeling; (2) supply chain issues; and, (3) other issues. FDA may use the information received to develop...? B. Supply Chain Issues 3. What are the supply chain factors (including storage, shipping, and... the optimal point in the supply chain (e.g., newly manufactured product, newly shipped product) and...

Polymorphic SSR markers for Plasmopara obducens (Peronosporaceae), the newly emergent downy mildew pathogen of Impatiens (Balsaminaceae)

USDA-ARS?s Scientific Manuscript database

Premise of the study: Microsatellite markers were developed for Plasmopara obducens, the causal agent of the newly emergent downy mildew disease of Impatiens walleriana. Methods and Results: A 151.2 Mb draft genome assembly was generated from P. obducens using Illumina technology and mined to identi...

Efficacy of Intra-articular Injection of a Newly Developed Plasma Rich in Growth Factor (PRGF) Versus Hyaluronic Acid on Pain and Function of Patients with Knee Osteoarthritis: A Single-Blinded Randomized Clinical Trial.

PubMed

Raeissadat, Seyed Ahmad; Rayegani, Seyed Mansoor; Ahangar, Azadeh Gharooee; Abadi, Porya Hassan; Mojgani, Parviz; Ahangar, Omid Gharooi

2017-01-01

Knee osteoarthritis is the most common joint disease. We aimed to compare the efficacy and safety of intra-articular injection of a newly developed plasma rich in growth factor (PRGF) versus hyaluronic acid (HA) on pain and function of patients with knee osteoarthritis. In this single-blinded randomized clinical trial, patients with symptomatic osteoarthritis of knee were assigned to receive 2 intra-articular injections of our newly developed PRGF in 3 weeks or 3 weekly injections of HA. Our primary outcome was the mean change from baseline until 2 and 6 months post intervention in scores of visual analog scale, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and Lequesne index. We used analysis of variance for repeated-measures statistical test. A total of 69 patients entered final analysis. The mean age of patients was 58.2 ± 7.41 years and 81.2% were women. In particular, total WOMAC index decreased from 42.9 ± 13.51 to 26.8 ± 13.45 and 24.4 ± 16.54 at 2 and 6 months in the newly developed PRGF group (within subjects P  = .001), and from 38.8 ± 12.62 to 27.8 ± 11.01 and 27.4 ± 11.38 at 2 and 6 months in the HA group (within subjects P  = .001), respectively (between subjects P  = .631). There was no significant difference between PRGF and HA groups in patients' satisfaction and minor complications of injection, whereas patients in HA group reported significantly lower injection-induced pain. In 6 months follow up, our newly developed PRGF and HA, both are effective options to decrease pain and improvement of function in patients with symptomatic mild to moderate knee osteoarthritis.

A Standardized Education Checklist for Parents of Children Newly Diagnosed With Cancer: A Report From the Children's Oncology Group.

PubMed

Rodgers, Cheryl; Bertini, Vanessa; Conway, Mary Ashe; Crosty, Ashley; Filice, Angela; Herring, Ruth Anne; Isbell, Julie; Lown DrPH, E Anne; Miller, Kristina; Perry, Margaret; Sanborn, Paula; Spreen, Nicole; Tena, Nancy; Winkle, Cindi; Darling, Joan; Slaven, Abigail; Sullivan, Jeneane; Tomlinson, Kathryn M; Windt, Kate; Hockenberry, Marilyn; Landier, Wendy

2018-03-01

Parents of children newly diagnosed with cancer must acquire new knowledge and skills in order to safely care for their child at home. Institutional variation exists in the methods and content used by nurses in providing the initial education. The goal of this project was to develop a checklist, standardized across institutions, to guide nursing education provided to parents of children newly diagnosed with cancer. A team of 21 members (19 nurses and 2 parent advocates) used current hospital educational checklists, expert consensus recommendations, and a series of iterative activities and discussions to develop one standardized checklist. The final checklist specifies primary topics that are essential to teach prior to the initial hospital discharge, secondary topics that should be discussed within the first month after the cancer diagnosis, and tertiary topics that should be discussed prior to completion of therapy. This checklist is designed to guide education and will set the stage for future studies to identify effective teaching strategies that optimize the educational process for parents of children newly diagnosed with cancer.

Category Coherence and Category-Based Property Induction

ERIC Educational Resources Information Center

Rehder, Bob; Hastie, Reid

2004-01-01

One important property of human object categories is that they define the sets of exemplars to which newly observed properties are generalized. We manipulated the causal knowledge associated with novel categories and assessed the resulting strength of property inductions. We found that the theoretical coherence afforded to a category by…

ENVIRONMENTAL EXPOSURES TO CHLOROPHENOXY HERBICIDES AND ASSOCIATION WITH ADVERSE HUMAN HEALTH EFFECTS: EXAMPLE OF THE NEED FOR BETTER METHODS

EPA Science Inventory

Previous studies have made the following observations: newly emerging global patterns of disease have been observed, and environmental exposures have been implicated. Ecologic studies are fundamental for the identification of public health problems. Some level of exposure in a...

Borrelia miyamotoi-Associated Neuroborreliosis in Immunocompromised Person.

PubMed

Boden, Katharina; Lobenstein, Sabine; Hermann, Beate; Margos, Gabriele; Fingerle, Volker

2016-09-01

Borrelia miyamotoi is a newly recognized human pathogen in the relapsing fever group of spirochetes. We investigated a case of B. miyamotoi infection of the central nervous system resembling B. burgdorferi-induced Lyme neuroborreliosis and determined that this emergent agent of central nervous system infection can be diagnosed with existing methods.

Building Schools, Rethinking Quality? Early Lessons from Los Angeles

ERIC Educational Resources Information Center

Fuller, Bruce; Dauter, Luke; Hosek, Adrienne; Kirschenbaum, Greta; McKoy, Deborah; Rigby, Jessica; Vincent, Jeffrey M.

2009-01-01

Purpose: Newly designed schools for centuries have projected fresh ideals regarding how children should learn and how human settlements should be organized. But under what conditions can forward-looking architects or education reformers trump the institutionalized practices of teachers or the political-economic constraints found within urban…

Draft Genome Sequence of Enterococcus faecium Strain J19, Isolated from Cabbage

PubMed Central

2018-01-01

ABSTRACT Herein, we report the draft genome sequence of a newly discovered probiotic strain, Enterococcus faecium J19, which was isolated from cabbage. Strain J19 has shown antagonistic effects against the human foodborne pathogen Listeria monocytogenes in coculture and in different food matrices. PMID:29622613

Battle against cancer: an everlasting saga of p53.

PubMed

Hao, Qian; Cho, William C

2014-12-01

Cancer is one of the most life-threatening diseases characterized by uncontrolled growth and spread of malignant cells. The tumor suppressor p53 is the master regulator of tumor cell growth and proliferation. In response to various stress signals, p53 can be activated and transcriptionally induces a myriad of target genes, including both protein-encoding and non-coding genes, controlling cell cycle progression, DNA repair, senescence, apoptosis, autophagy and metabolism of tumor cells. However, around 50% of human cancers harbor mutant p53 and, in the majority of the remaining cancers, p53 is inactivated through multiple mechanisms. Herein, we review the recent progress in understanding the molecular basis of p53 signaling, particularly the newly identified ribosomal stress-p53 pathway, and the development of chemotherapeutics via activating wild-type p53 or restoring mutant p53 functions in cancer. A full understanding of p53 regulation will aid the development of effective cancer treatments.

An automated microphysiological assay for toxicity evaluation.

PubMed

Eggert, S; Alexander, F A; Wiest, J

2015-08-01

Screening a newly developed drug, food additive or cosmetic ingredient for toxicity is a critical preliminary step before it can move forward in the development pipeline. Due to the sometimes dire consequences when a harmful agent is overlooked, toxicologists work under strict guidelines to effectively catalogue and classify new chemical agents. Conventional assays involve long experimental hours and many manual steps that increase the probability of user error; errors that can potentially manifest as inaccurate toxicology results. Automated assays can overcome many potential mistakes that arise due to human error. In the presented work, we created and validated a novel, automated platform for a microphysiological assay that can examine cellular attributes with sensors measuring changes in cellular metabolic rate, oxygen consumption, and vitality mediated by exposure to a potentially toxic agent. The system was validated with low buffer culture medium with varied conductivities that caused changes in the measured impedance on integrated impedance electrodes.

Medical Rejuvenation in Georgia in the past: the Sukhumi Station.

PubMed

Musajo-Somma, Laura; Musajo-Somma, Alfredo

2016-12-01

If youth and body appearance enhancement is as old as Homo Sapiens, reliable medical technology for such activities is only about 100 years old. At the dawn of the 20th century, surgical operations performed under the Voronoff's treatment plan (monkey gonads' tissue grafting into humans) or the Steinach's technique (vasoligation) offered a promise of longevity, beauty and therefore youth restoration. The many links with a newly recognized discipline, endocrinology, offer a critical insight on the strong interactions between medicine and surgery in the promise of successful antiaging. On the front-line of scientific research, the Institute of Experimental Endocrinology's primate station in Sukhumi (West Georgia, now Abkhazia, on the Black Sea coast) developed a leadership role in the medical research, including rejuvenation with testis' tissues. Authors focus their attention to the everlasting commitment to experimental and clinical research as developed by Sukhumi scholars and the related moral, practical and ideological implications.

Deterministic binary vectors for efficient automated indexing of MEDLINE/PubMed abstracts.

PubMed

Wahle, Manuel; Widdows, Dominic; Herskovic, Jorge R; Bernstam, Elmer V; Cohen, Trevor

2012-01-01

The need to maintain accessibility of the biomedical literature has led to development of methods to assist human indexers by recommending index terms for newly encountered articles. Given the rapid expansion of this literature, it is essential that these methods be scalable. Document vector representations are commonly used for automated indexing, and Random Indexing (RI) provides the means to generate them efficiently. However, RI is difficult to implement in real-world indexing systems, as (1) efficient nearest-neighbor search requires retaining all document vectors in RAM, and (2) it is necessary to maintain a store of randomly generated term vectors to index future documents. Motivated by these concerns, this paper documents the development and evaluation of a deterministic binary variant of RI. The increased capacity demonstrated by binary vectors has implications for information retrieval, and the elimination of the need to retain term vectors facilitates distributed implementations, enhancing the scalability of RI.

Deterministic Binary Vectors for Efficient Automated Indexing of MEDLINE/PubMed Abstracts

PubMed Central

Wahle, Manuel; Widdows, Dominic; Herskovic, Jorge R.; Bernstam, Elmer V.; Cohen, Trevor

2012-01-01

The need to maintain accessibility of the biomedical literature has led to development of methods to assist human indexers by recommending index terms for newly encountered articles. Given the rapid expansion of this literature, it is essential that these methods be scalable. Document vector representations are commonly used for automated indexing, and Random Indexing (RI) provides the means to generate them efficiently. However, RI is difficult to implement in real-world indexing systems, as (1) efficient nearest-neighbor search requires retaining all document vectors in RAM, and (2) it is necessary to maintain a store of randomly generated term vectors to index future documents. Motivated by these concerns, this paper documents the development and evaluation of a deterministic binary variant of RI. The increased capacity demonstrated by binary vectors has implications for information retrieval, and the elimination of the need to retain term vectors facilitates distributed implementations, enhancing the scalability of RI. PMID:23304369

Surface reactivity measurements as required for grouping and read-across: An advanced FRAS protocol

NASA Astrophysics Data System (ADS)

Gandon, Arnaud; Werle, Kai; Neubauer, Nicole; Wohlleben, Wendel

2017-06-01

Oxidative stress is a widely accepted paradigm associated with different adverse outcomes of particulate matter, including nanomaterials. It has frequently been identified in in vitro and in vivo studies and different assays have been developed for this purpose. Here we describe a newly developed multi-dose protocol of the FRAS assay (Ferric Reduction Ability of Serum). The purpose of this SOP is the measurement of the surface reactivity of nanomaterials under physiological conditions. Antioxidative components as present in human blood serum (HBS) serve as reporter molecules. The assay separates the oxidative damage from the read-out of the reporter molecules. The results show significantly enhanced repeatability with better sensitivity towards low reactivity, enabling application of FRAS both to a rough grouping by reactive vs. passive nanomaterials and further to substantiation of read-across by enhanced resolution of the similarity between different nanoforms of the same substance.

In vitro analysis of polyurethane foam as a topical hemostatic agent.

PubMed

Broekema, Ferdinand I; van Oeveren, Wim; Zuidema, Johan; Visscher, Susan H; Bos, Rudolf R M

2011-04-01

Topical hemostatic agents can be used to treat problematic bleedings in patients who undergo surgery. Widely used are the collagen- and gelatin-based hemostats. This study aimed to develop a fully synthetic, biodegradable hemostatic agent to avoid exposure to animal antigens. In this in vitro study the suitability of different newly developed polyurethane-based foams as a hemostatic agent has been evaluated and compared to commonly used agents. An experimental in vitro test model was used in which human blood flowed through the test material. Different modified polyurethane foams were compared to collagen and gelatin. The best coagulation was achieved with collagen. The results of the polyurethane foam improved significantly by increasing the amount of polyethylene glycol. Therefore, the increase of the PEG concentration seems a promising approach. Additional in vivo studies will have to be implemented to assess the application of polyurethane foam as a topical hemostatic agent.

Human Computation in Visualization: Using Purpose Driven Games for Robust Evaluation of Visualization Algorithms.

PubMed

Ahmed, N; Zheng, Ziyi; Mueller, K

2012-12-01

Due to the inherent characteristics of the visualization process, most of the problems in this field have strong ties with human cognition and perception. This makes the human brain and sensory system the only truly appropriate evaluation platform for evaluating and fine-tuning a new visualization method or paradigm. However, getting humans to volunteer for these purposes has always been a significant obstacle, and thus this phase of the development process has traditionally formed a bottleneck, slowing down progress in visualization research. We propose to take advantage of the newly emerging field of Human Computation (HC) to overcome these challenges. HC promotes the idea that rather than considering humans as users of the computational system, they can be made part of a hybrid computational loop consisting of traditional computation resources and the human brain and sensory system. This approach is particularly successful in cases where part of the computational problem is considered intractable using known computer algorithms but is trivial to common sense human knowledge. In this paper, we focus on HC from the perspective of solving visualization problems and also outline a framework by which humans can be easily seduced to volunteer their HC resources. We introduce a purpose-driven game titled "Disguise" which serves as a prototypical example for how the evaluation of visualization algorithms can be mapped into a fun and addicting activity, allowing this task to be accomplished in an extensive yet cost effective way. Finally, we sketch out a framework that transcends from the pure evaluation of existing visualization methods to the design of a new one.

The Minimal Preprocessing Pipelines for the Human Connectome Project

PubMed Central

Glasser, Matthew F.; Sotiropoulos, Stamatios N; Wilson, J Anthony; Coalson, Timothy S; Fischl, Bruce; Andersson, Jesper L; Xu, Junqian; Jbabdi, Saad; Webster, Matthew; Polimeni, Jonathan R; Van Essen, David C; Jenkinson, Mark

2013-01-01

The Human Connectome Project (HCP) faces the challenging task of bringing multiple magnetic resonance imaging (MRI) modalities together in a common automated preprocessing framework across a large cohort of subjects. The MRI data acquired by the HCP differ in many ways from data acquired on conventional 3 Tesla scanners and often require newly developed preprocessing methods. We describe the minimal preprocessing pipelines for structural, functional, and diffusion MRI that were developed by the HCP to accomplish many low level tasks, including spatial artifact/distortion removal, surface generation, cross-modal registration, and alignment to standard space. These pipelines are specially designed to capitalize on the high quality data offered by the HCP. The final standard space makes use of a recently introduced CIFTI file format and the associated grayordinates spatial coordinate system. This allows for combined cortical surface and subcortical volume analyses while reducing the storage and processing requirements for high spatial and temporal resolution data. Here, we provide the minimum image acquisition requirements for the HCP minimal preprocessing pipelines and additional advice for investigators interested in replicating the HCP’s acquisition protocols or using these pipelines. Finally, we discuss some potential future improvements for the pipelines. PMID:23668970

Genetic testing for patients with renal disease: procedures, pitfalls, and ethical considerations.

PubMed

Korf, B R

1999-07-01

The Human Genome Project is rapidly producing insights into the molecular basis of human genetic disorders. The most immediate clinical benefit is the advent of new diagnostic methods. Molecular diagnostic tools are available for several genetic renal disorders and are in development for many more. Two general approaches to molecular diagnosis are linkage-based testing and direct mutation detection. The former is used when the gene has not been cloned but has been mapped in relation to polymorphic loci. Linkage-based testing is also helpful when a large diversity of mutations makes direct detection difficult. Limitations include the need to study multiple family members, the need for informative polymorphisms, and genetic heterogeneity. Direct mutation detection is limited by genetic heterogeneity and the need to distinguish nonpathogenic allelic variants from pathogenic mutations. Molecular testing raises a number of complex ethical issues, including those associated with prenatal or presymptomatic diagnosis. In addition, there are concerns about informed consent, privacy, genetic discrimination, and technology transfer for newly developed tests. Health professionals need to be aware of the technical and ethical implications of these new methods of testing, as well as the complexities in test interpretation, as molecular approaches are increasingly integrated into medical practice.

Hiding in Plain Sight: Rediscovering the Importance of Noncoding RNA in Human Malignancy.

PubMed

Feeley, Kyle P; Edmonds, Mick D

2018-05-01

At the time of its construction in the 1950s, the central dogma of molecular biology was a useful model that represented the current state of knowledge for the flow of genetic information after a period of prolific scientific discovery. Unknowingly, it also biased many of our assumptions going forward. Whether intentional or not, genomic elements not fitting into this paradigm were deemed unimportant and emphasis on the study of protein-coding genes prevailed for decades. The phrase "Junk DNA," first popularized in the 1960s, is still used with alarming frequency to describe the entirety of noncoding DNA. It has since become apparent that RNA molecules not coding for protein are vitally important in both normal development and human malignancy. Cancer researchers have been pioneers in determining noncoding RNA function and developing new technologies to study these molecules. In this review, we will discuss well known and newly emerging species of noncoding RNAs, their functions in cancer, and new technologies being utilized to understand their mechanisms of action in cancer. Cancer Res; 78(9); 2149-58. ©2018 AACR . ©2018 American Association for Cancer Research.

Solid-Phase Extraction of Sulfur Mustard Metabolites Using an Activated Carbon Fiber Sorbent.

PubMed

Lee, Jin Young; Lee, Yong Han

2016-01-01

A novel solid-phase extraction method using activated carbon fiber (ACF) was developed and validated. ACF has a vast network of pores of varying sizes and microporous structures that result in rapid adsorption and selective extraction of sulfur mustard metabolites according to the pH of eluting solvents. ACF could not only selectively extract thiodiglycol and 1-methylsulfinyl-2-[2-(methylthio)-ethylsulfonyl]ethane eluting a 9:1 ratio of dichloromethane to acetone, and 1,1'-sulfonylbis[2-(methylsulfinyl)ethane] and 1,1'-sulfonylbis- [2-S-(N-acetylcysteinyl)ethane] eluting 3% hydrogen chloride in methanol, but could also eliminate most interference without loss of analytes during the loading and washing steps. A sample preparation method has been optimized for the extraction of sulfur mustard metabolites from human urine using an ACF sorbent. The newly developed extraction method was applied to the trace analysis of metabolites of sulfur mustard in human urine matrices in a confidence-building exercise for the analysis of biomedical samples provided by the Organisation for the Prohibition of Chemical Weapons. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Proteomic analysis of single mammalian cells enabled by microfluidic nanodroplet sample preparation and ultrasensitive nanoLC-MS.

PubMed

Zhu, Ying; Clair, Geremy; Chrisler, William; Shen, Yufeng; Zhao, Rui; Shukla, Anil; Moore, Ronald; Misra, Ravi; Pryhuber, Gloria; Smith, Richard; Ansong, Charles; Kelly, Ryan T

2018-05-24

We report on the quantitative proteomic analysis of single mammalian cells. Fluorescence-activated cell sorting was employed to deposit cells into a newly developed nanodroplet sample processing chip, after which samples were analysed by ultrasensitive nanoLC-MS. An average of ~670 protein groups were confidently identified from single HeLa cells, which is a far greater level of proteome coverage for single cells than has been previously reported. We demonstrate that the single cell proteomics platform can be used to differentiate cell types from enzyme-dissociated human lung primary cells and identify specific protein markers for epithelial and mesenchymal cells. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The ongoing evolution of antibody-based treatments for Ebola virus infection.

PubMed

Mendoza, Emelissa J; Racine, Trina; Kobinger, Gary P

2017-03-01

The 2014-2016 Ebola virus outbreak in West Africa was the deadliest in history, prompting the evaluation of various drug candidates, including antibody-based therapeutics for the treatment of Ebola hemorrhagic fever (EHF). Prior to 2014, only convalescent blood products from EHF survivors had been administered to newly infected individuals as a form of treatment. However, during the recent outbreak, monoclonal antibody cocktails such as ZMapp, ZMAb and MB-003 were either tested in a human clinical safety and efficacy trial or provided to some based on compassionate grounds. This review aims to discuss the evolution of antibody-based treatments for EHF, their clinical trial efficacy and the development of new antibody-based therapies currently advancing in preclinical testing.

Vitamin A supplementation increases levels of retinoic acid compounds in human plasma: possible implications for teratogenesis.

PubMed

Eckhoff, C; Nau, H

1990-01-01

The concentrations of retinoic acid compounds were monitored by a newly developed highly sensitive HPLC procedure in plasma of six volunteers who received 833 IU vitamin A per kg body weight per day during a 20-day period. There was a significant increase of all-trans-retinoic acid (two-fold), 13-cis-retinoic acid (7-fold) and 13-cis-4-oxoretinoic acid (5-fold) over endogenous plasma levels of these retinoids. The same compounds had previously been found after treatment with the teratogenic drug isotretinoin (Roaccutan, Accutane). Our results raise the possibility that high vitamin A intake may carry a teratogenic risk attributable to increased levels of retinoic acid compounds generated from retinol by metabolic processes.

Wireless energy transfer platform for medical sensors and implantable devices.

PubMed

Zhang, Fei; Hackworth, Steven A; Liu, Xiaoyu; Chen, Haiyan; Sclabassi, Robert J; Sun, Mingui

2009-01-01

Witricity is a newly developed technique for wireless energy transfer. This paper presents a frequency adjustable witricity system to power medical sensors and implantable devices. New witricity resonators are designed for both energy transmission and reception. A prototype platform is described, including an RF power source, two resonators with new structures, and inductively coupled input and output stages. In vitro experiments, both in open air and using a human head phantom consisting of simulated tissues, are employed to verify the feasibility of this platform. An animal model is utilized to evaluate in vivo energy transfer within the body of a laboratory pig. Our experiments indicate that witricity is an effective new tool for providing a variety of medical sensors and devices with power.

Pathophysiology of luteal-phase deficiency in human reproduction.

PubMed

Nakajima, S T; Gibson, M

1991-03-01

There are numerous probable mechanisms for the clinical occurrence of a luteal-phase deficiency. Defects may occur in either the proliferative, luteal, or luteal-rescue stage of a menstrual cycle. In each of these three domains, alterations in the trophic stimulation or the response at either the ovarian or endometrial level further subdivide the etiologies for luteal-phase deficiency. Additional development of new concepts in the areas of intraovarian signaling, the possible role of growth factors, and the measurement of newly discovered luteal products will enable us to expand our thought process. With a better understanding of the pathophysiology of luteal-phase deficiency, it is anticipated that new treatments will be devised to address precisely a given specific etiologic factor.

Preparation and in vitro screening of symmetrical bis-isoquinolinium cholinesterase inhibitors bearing various connecting linkage--implications for early Myasthenia gravis treatment.

PubMed

Musilek, Kamil; Komloova, Marketa; Holas, Ondrej; Hrabinova, Martina; Pohanka, Miroslav; Dohnal, Vlastimil; Nachon, Florian; Dolezal, Martin; Kuca, Kamil

2011-02-01

Inhibitors of acetylcholinesterase are compounds widely used in the treatment of various diseases, such as Alzheimer's disease, glaucoma and Myasthenia gravis (MG). Compounds used in the therapy of MG posses a positive charge in the molecule to ensure peripheral effect of action and minimal blood-brain barrier penetration. The most prescribed carbamate inhibitors are however known for many severe side effects related to the carbamylation of AChE. This paper describes preparation and in vitro evaluation of 20 newly prepared bis-isoquinolinium inhibitors of potential concern for MG. The newly prepared compounds were evaluated in vitro on human recombinant AChE and human plasmatic butyrylcholinesterase (BChE). Their inhibitory ability was expressed as IC50 and compared to chosen standards ambenonium dichloride, edrophonium chloride, BW284c51 and ethopropazine hydrochloride. Three novel compounds presented promising inhibition (in nM range) of both enzymes in vitro better or similar to edrophonium and BW284c51, but worse to ambenonium. The novel inhibitors did not present higher selectivity toward AChE or BChE. The kinetic assay confirmed non-competitive inhibition of hAChE by two selected promising novel compounds. Two newly prepared compounds were also chosen for docking studies that confirmed apparent π-π or π-cationic interactions aside the cholinesterases catalytic sites. The SAR findings were discussed. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

Longitudinal Analysis of Carcinogenic Human Papillomavirus Infection and Associated Cytologic Abnormalities in the Guanacaste Natural History Study: Looking Ahead to Cotesting

PubMed Central

Rodriguez, Ana C.; Burk, Robert D.; Hildesheim, Allan; Herrero, Rolando; Wacholder, Sholom; Hutchinson, Martha; Schiffman, Mark

2012-01-01

Background. Few studies have addressed the timing of cervical cytologic abnormalities and human papillomavirus (HPV) positivity during the course of an infection. It remains largely unknown how infections detected by HPV and cytology wax and wane relative to each other. The aim of this analysis was to assess the longitudinal relationship of abnormal cytology and HPV positivity in a 7-year prospective study of 2500 women in Guanacaste, Costa Rica. Methods. At each semiannual or annual visit, cervical specimens were screened using liquid-based cytology and tested for >40 HPV types with use of MY09/MY11 L1 degenerate primer polymerase chain reaction–based methods. On the basis of previous work, we separated prevalent and newly detected infections in younger and older women. Results. Among newly detected HPV- and/or cytology-positive events, HPV and cytology appeared together ∼60% of the time; when discordant, HPV tended to appear before cytology in younger and older women. Combining newly and prevalently detected events, HPV and cytology disappeared at the same time >70% of the time. When discordant, HPV tended to disappear after cytology in younger and older women. Conclusions. Detection of HPV DNA and associated cytological abnormalities tend to come and leave together; however, when discordant, detection of HPV DNA tends to precede and/or last longer than associated cytologic abnormalities. PMID:22147792

Newly-synthesized chalcones-inhibition of adherence and biofilm formation of methicillin-resistant Staphylococcus aureus

PubMed Central

Bozic, Dragana D.; Milenkovic, Marina; Ivkovic, Branka; Cirkovic, Ivana

2014-01-01

Biofilm formation and adherence of bacteria to host tissue are one of the most important virulence factors of methicillin-resistant strains of Staphylococcus aureus (MRSA). The number of resistant strains is seriously increasing during the past years and bacteria have become resistant, not only to methicillin, but also to other commonly used antistaphylococcal antibiotics. There is a great need for discovering a novel antimicrobial agent for the treatment of staphylococcal infections. One of the most promising groups of compounds appears to be chalcones. In present study we evaluated the in vitro effect of three newly synthesized chalcones: 1,3- Bis-(2-hydroxy-phenyl)-propenone, 3-(3-Hydroxy-phenyl)-1-(2-hydroxy-phenyl)-propenone and 3-(4-Hydroxy-phenyl)-1-(2-hydroxy-phenyl)-propenone on glycocalyx production, biofilm formation and adherence to human fibronectin of clinical isolates and laboratory control strain of MRSA (ATCC 43300). Subinhibitory concentrations of the tested compounds reduced the production of glycocalyx, biofilm formation and adherence to human fibronectin of all MRSA strains. Inhibition of biofilm formation was dose dependent and the most effective was 1,3- Bis-(2-hydroxy-phenyl)-propenone. In our study we demonstrated that three newly-synthesized chalcones exhibited significant effect on adherence and biofilm formation of MRSA strains. Chalcones may be considered as promising new antimicrobial agents that can be used for prevention of staphylococcal infections or as adjunct to antibiotics in conventional therapy. PMID:24948943

Development of a Highly Biocompatible Antituberculosis Nanodelivery Formulation Based on Para-Aminosalicylic Acid—Zinc Layered Hydroxide Nanocomposites

PubMed Central

Arulselvan, Palanisamy; El Zowalaty, Mohamed Ezzat; Fakurazi, Sharida; Webster, Thomas J.; Geilich, Benjamin; Hussein, Mohd Zobir

2014-01-01

Tuberculosis is a lethal epidemic, difficult to control disease, claiming thousands of lives every year. We have developed a nanodelivery formulation based on para-aminosalicylic acid (PAS) and zinc layered hydroxide using zinc nitrate salt as a precursor. The developed formulation has a fourfold higher efficacy of PAS against mycobacterium tuberculosis with a minimum inhibitory concentration (MIC) found to be at 1.40 μg/mL compared to the free drug PAS with a MIC of 5.0 μg/mL. The newly developed formulation was also found active against Gram-positive bacteria, Gram-negative bacteria, and Candida albicans. The formulation was also found to be biocompatible with human normal lung cells MRC-5 and mouse fibroblast cells-3T3. The in vitro release of PAS from the formulation was found to be sustained in a human body simulated phosphate buffer saline (PBS) solution at pH values of 7.4 and 4.8. Most importantly the nanocomposite prepared using zinc nitrate salt was advantageous in terms of yield and free from toxic zinc oxide contamination and had higher biocompatibility compared to one prepared using a zinc oxide precursor. In summary, these promising in vitro results are highly encouraging for the continued investigation of para-aminosalicylic acid and zinc layered hydroxide nanocomposites in vivo and eventual preclinical studies. PMID:25050392

Analysis of non-esterified fatty acids in human samples by solid-phase-extraction and gas chromatography/mass spectrometry.

PubMed

Kopf, Thomas; Schmitz, Gerd

2013-11-01

The determination of the fatty acid (FA) profile of lipid classes is essential for lipidomic analysis. We recently developed a GC/MS-method for the analysis of the FA profile of total FAs, i.e. the totality of bound and unbound FAs, in any given biological sample (TOFAs). Here, we present a method for the analysis of non-esterified fatty acids (NEFAs) in biological samples, i.e. the fraction that is present as extractable free fatty acids. Lipid extraction is performed according to Dole using 80/20 2-propanol/n-hexane (v/v), with 0.1% H2SO4. The fatty acid-species composition of this NEFA-fraction is determined as FAME after derivatization with our GC/MS-method on a BPX column (Shimadzu). Validation of the NEFA-method presented was performed in human plasma samples. The validated method has been used with human plasma, cells and tissues, as well as mammalian body fluids and tissue samples. The newly developed solid-phase-extraction (SPE)-GC-MS method allows the rapid separation of the NEFA-fraction from a neutral lipid extract of plasma samples. As a major advantage compared to G-FID-methods, GC-MS allows the use of stable isotope labeled fatty acid precursors to monitor fatty acid metabolism. Copyright © 2013 Elsevier B.V. All rights reserved.

Integrated Multivariate Analysis with Nondetects for the Development of Human Sewage Source-Tracking Tools Using Bacteriophages of Enterococcus faecalis.

PubMed

Wangkahad, Bencharong; Mongkolsuk, Skorn; Sirikanchana, Kwanrawee

2017-02-21

We developed sewage-specific microbial source tracking (MST) tools using enterococci bacteriophages and evaluated their performance with univariate and multivariate analyses involving data below detection limits. Newly isolated Enterococci faecalis bacterial strains AIM06 (DSM100702) and SR14 (DSM100701) demonstrated 100% specificity and 90% sensitivity to human sewage without detecting 68 animal manure pooled samples of cats, chickens, cows, dogs, ducks, pigs, and pigeons. AIM06 and SR14 bacteriophages were present in human sewage at 2-4 orders of magnitude. A principal component analysis confirmed the importance of both phages as main water quality parameters. The phages presented only in the polluted water, as classified by a cluster analysis, and at median concentrations of 1.71 × 10 2 and 4.27 × 10 2 PFU/100 mL, respectively, higher than nonhost specific RYC2056 phages and sewage-specific KS148 phages (p < 0.05). Interestingly, AIM06 and SR14 phages exhibited significant correlations with each other and with total coliforms, E. coli, enterococci, and biochemical oxygen demand (Kendall's tau = 0.348 to 0.605, p < 0.05), a result supporting their roles as water quality indicators. This research demonstrates the multiregional applicability of enterococci hosts in MST application and highlights the significance of multivariate analysis with nondetects in evaluating the performance of new MST host strains.

The use of newly developed real-time PCR for the rapid identification of bacteria in culture-negative osteomyelitis.

PubMed

Kobayashi, Naomi; Bauer, Thomas W; Sakai, Hiroshige; Togawa, Daisuke; Lieberman, Isador H; Fujishiro, Takaaki; Procop, Gary W

2006-12-01

We report a case of a culture-negative osteomyelitis in which our newly developed real-time polymerase chain reaction (PCR) could differentiate Staphylococcus aureus from Staphylococcus epidermidis. This is the first report that described the application of this novel assay to an orthopedics clinical sample. This assay may be useful for other clinical culture-negative cases in a combination with a broad-spectrum assay as a rapid microorganism identification method.

What did the Romans ever do for us? Putting humans in global land models

NASA Astrophysics Data System (ADS)

Bierkens, M. F.; Wada, Y.; Dermody, B.; Van Beek, L. P.

2016-12-01

During the late 1980s and early 1990s, awareness of the shortage of global water resources lead to the first detailed global water resources assessments using regional statistics of water use and observations of meteorological and hydrological variables. Shortly thereafter, the first macroscale hydrological models (MHM) appeared. In these models, blue water (i.e., surface water and renewable groundwater) availability was calculated by accumulating runoff over a stream network and comparing it with population densities or with estimated water demand for agriculture, industry and households. In this talk we review the evolution of human impact modelling in global land models with a focus on global water resources, touching upon developments of the last 15 years: i.e. calculating human water scarcity; estimating groundwater depletion; adding dams and reservoirs; fully integrating water use (abstraction, application, consumption, return flow) in the hydrology; simulating the effects of land use change. We identify four major challenges that hamper the further development of integrated water resources modelling and thus prohibit realistic projections of the future terrestrial water cycle in the Anthropocene. These are: 1) including the ability to model infrastructural changes and measures; 2) projecting future water demand and water use and associated measures; 3) including virtual water trade; 4) including land use change and landscape change. While all these challenges will likely benefit from hydro-economics and the newly developing field of socio-hydrology, we also show that especially for challenges 3 and 4 lessons can be drawn from the (pre)historic past. To make this point we provide two case studies: one modelling the virtual water trade in the Roman Empire and one modelling human-landscape interaction in prehistoric Calabria (Italy).

Determination of fluvoxamine maleate in human urine and human serum using alkaline KMnO4 -rhodamine B chemiluminescence.

PubMed

Yang, Dongqin; He, Yanyan; Chen, Funan

2017-09-01

The flow-injection chemiluminescence (FI-CL) behavior of a gold nanocluster (Au NC)-enhanced rhodamine B-KMnO 4 system was studied under alkaline conditions for the first time. In the present study, the as-prepared bovine serum albumin-stabilized Au NCs showed excellent stability and reproducibility. The addition of trace levels of fluvoxamine maleate (Flu) led to an obvious decline in CL intensity in the rhodamine B-KMnO 4 -Au NCs system, which could be used for quantitative detection of Flu. Under optimized conditions, the proposed CL system exhibited a favorable analytical performance for Flu determination in the range 2 to 100 μg ml -1 . The detection limit for Flu measurement was 0.021 μg ml -1 . Moreover, this newly developed system revealed outstanding selectivity for Flu detection when compared with a multitude of other species, such as the usual ions, uric acid and a section of hydroxy compounds. Additionally, CL spectra, UV-visible spectroscopes and fluorescence spectra were measured in order to determine the possible reaction mechanism. This approach could be used to detect Flu in human urine and human serum samples with the desired recoveries and could have promising application under physiological conditions. Copyright © 2017 John Wiley & Sons, Ltd.

Lnc2Cancer: a manually curated database of experimentally supported lncRNAs associated with various human cancers

PubMed Central

Ning, Shangwei; Zhang, Jizhou; Wang, Peng; Zhi, Hui; Wang, Jianjian; Liu, Yue; Gao, Yue; Guo, Maoni; Yue, Ming; Wang, Lihua; Li, Xia

2016-01-01

Lnc2Cancer (http://www.bio-bigdata.net/lnc2cancer) is a manually curated database of cancer-associated long non-coding RNAs (lncRNAs) with experimental support that aims to provide a high-quality and integrated resource for exploring lncRNA deregulation in various human cancers. LncRNAs represent a large category of functional RNA molecules that play a significant role in human cancers. A curated collection and summary of deregulated lncRNAs in cancer is essential to thoroughly understand the mechanisms and functions of lncRNAs. Here, we developed the Lnc2Cancer database, which contains 1057 manually curated associations between 531 lncRNAs and 86 human cancers. Each association includes lncRNA and cancer name, the lncRNA expression pattern, experimental techniques, a brief functional description, the original reference and additional annotation information. Lnc2Cancer provides a user-friendly interface to conveniently browse, retrieve and download data. Lnc2Cancer also offers a submission page for researchers to submit newly validated lncRNA-cancer associations. With the rapidly increasing interest in lncRNAs, Lnc2Cancer will significantly improve our understanding of lncRNA deregulation in cancer and has the potential to be a timely and valuable resource. PMID:26481356

Development and Assessment of Transgenic Rodent Parasites for the Preclinical Evaluation of Malaria Vaccines.

PubMed

Espinosa, Diego A; Radtke, Andrea J; Zavala, Fidel

2016-01-01

Rodent transgenic parasites are useful tools for the preclinical evaluation of malaria vaccines. Over the last decade, several studies have reported the development of transgenic rodent parasites expressing P. falciparum antigens for the assessment of vaccine-induced immune responses, which traditionally have been limited to in vitro assays. However, the genetic manipulation of rodent Plasmodium species can have detrimental effects on the parasite's infectivity and development. In this chapter, we present a few guidelines for designing transfection plasmids, which should improve transfection efficiency and facilitate the generation of functional transgenic parasite strains. In addition, we provide a transfection protocol for the development of transgenic P. berghei parasites as well as practical methods to assess the viability and infectivity of these newly generated strains throughout different stages of their life cycle. These techniques should allow researchers to develop novel rodent malaria parasites expressing antigens from human malaria species and to determine whether these transgenic strains are fully infectious and thus represent stringent platforms for the in vivo evaluation of malaria vaccine candidates.

Being a team leader: newly registered nurses relate their experiences.

PubMed

Ekström, Louise; Idvall, Ewa

2015-01-01

This paper presents a study that explores how newly qualified registered nurses experience their leadership role in the ward-based nursing care team. A nurse's clinical leadership affects the quality of care provided. Newly qualified nurses experience difficulties during the transition period from student to qualified professional and find it challenging to lead nursing care. Twelve nurses were interviewed and the transcribed texts analysed using qualitative content analysis to assess both manifest and latent content. Five themes were identified: feeling stranded; forming well-functioning teams; learning to lead; having the courage, strength, and desire to lead; and ensuring appropriate care. The findings indicate that many factors limit nurses' leadership but some circumstances are supportive. The leadership prerequisites for newly registered nurses need to improve, emphasizing different ways to create a supportive atmosphere that promotes professional development and job satisfaction. To increase nurse retention and promote quality of care, nurse managers need to clarify expectations and guide and support newly qualified nurses in a planned way. © 2013 John Wiley & Sons Ltd.

Recent developments in anti-cancer agents targeting PI3K, Akt and mTORC1/2.

PubMed

Dienstmann, Rodrigo; Rodon, Jordi; Markman, Ben; Tabernero, Josep

2011-05-01

Inappropriate PI3K signaling is one of the most frequent occurrences in human cancer and is critical for tumor progression. A variety of genetic mutations and amplifications have been described affecting key components of this pathway, with implications not only for tumorigenesis but also for resistance to targeted agents. Emerging preclinical research has significantly advanced our understanding of the PI3K pathway and its complex downstream signalling, interactions and crosstalk. This knowledge, combined with the limited clinical antitumor activity of mTOR complex 1 inhibitors, has led to the development of rationally designed drugs targeting key elements of this pathway, such as pure PI3K inhibitors (both pan-PI3K and isoform-specific), dual PI3K/ mTOR inhibitors, Akt inhibitors, and mTOR complexes 1 and 2 catalytic site inhibitors. This review will focus primarily on an analysis of newly developed inhibitors of this pathway that have entered clinical trials, and recently registered patents in this field.

Development of microsatellite markers for Viscum coloratum (Santalaceae) and their application to wild populations1

PubMed Central

Kim, Bo-Yun; Park, Han-Sol; Kim, Soonok; Kim, Young-Dong

2017-01-01

Premise of the study: Microsatellite primers were developed for Viscum coloratum (Santalaceae), a semiparasitic medicinal plant that is known for its anticancer properties. Due to excessive human harvesting and loss of suitable habitat of its populations, it has become a potentially threatened species requiring immediate conservation efforts. Methods and Results: Based on transcriptome data for V. coloratum, 124 primer pairs were randomly selected for initial validation, of which 19 yielded polymorphic microsatellite loci, with two to six alleles per locus. The usefulness of these markers was assessed for 60 individuals representing three populations of V. coloratum. Observed and expected heterozygosity values ranged from 0.033 to 0.833 and 0.032 to 0.672, respectively. Cross-species amplification for 19 loci in the related species V. album was conducted. Conclusions: The 19 newly developed loci are expected to be useful for studying the population genetics and ecological conservation of V. coloratum. PMID:28090408

Development of breeding populations of rhesus macaques (Macaca mulatta) that are specific pathogen-free for rhesus cytomegalovirus.

PubMed

Barry, Peter A; Strelow, Lisa

2008-02-01

Development of breeding colonies of rhesus macaques (Macaca mulatta) that are specific pathogen-free (SPF) for rhesus cytomegalovirus (RhCMV) is relatively straightforward and requires few modifications from current SPF programs. Infants separated from the dam at or within a few days of birth and cohoused with similarly treated animals remain RhCMV seronegative indefinitely, provided they are never directly or indirectly exposed to a RhCMV-infected monkey. By systematically cohousing seronegative animals into larger social cohorts, breeding populations of animals SPF for RhCMV can be established. The additional costs involved in expanding the current definition of SPF status to include RhCMV are incremental compared with the money already being spent on existing SPF efforts. Moreover, the large increase in research opportunities available for RhCMV-free animals arguably would far exceed the development costs. Potential new areas of research and further expansion of existing research efforts involving these newly defined SPF animals would have direct implications for improvements in human health.

Rapid tests for diagnosis of leptospirosis: current tools and emerging technologies.

PubMed

Picardeau, Mathieu; Bertherat, Eric; Jancloes, Michel; Skouloudis, Andreas N; Durski, Kara; Hartskeerl, Rudy A

2014-01-01

Leptospirosis is an emerging zoonosis with a worldwide distribution but is more commonly found in impoverished populations in developing countries and tropical regions with frequent flooding. The rapid detection of leptospirosis is a critical step to effectively manage the disease and to control outbreaks in both human and animal populations. Therefore, there is a need for accurate and rapid diagnostic tests and appropriate surveillance and alert systems to identify outbreaks. This review describes current in-house methods and commercialized tests for the rapid diagnosis of acute leptospirosis. It focuses on diagnostic tests that can be performed with minimal training and limited equipment in less-developed and newly industrialized countries, particularly in resource-limited settings and with results in minutes to less than 4 hours. We also describe recent technological advances in the field of diagnostic tests that could allow for the development of innovative rapid tests in the near future. © 2013 Elsevier Inc. All rights reserved.

VIRAL LOAD AND SHORT-TERM NATURAL HISTORY OF TYPE-SPECIFIC ONCOGENIC HUMAN PAPILLOMAVIRUS INFECTIONS IN A HIGH-RISK COHORT OF MID-ADULT WOMEN

PubMed Central

Winer, Rachel L.; Xi, Long Fu; Shen, Zhenping; Stern, Joshua E.; Newman, Laura; Feng, Qinghua; Hughes, James P.; Koutsky, Laura A.

2013-01-01

Oncogenic human papillomavirus (HPV) viral load may inform the origin of newly detected infections and characterize oncogenic HPV natural history in mid-adult women. From 2007–2011, we enrolled 521 25–65 year old female online daters and followed them triannually with mailed health and sexual behavior questionnaires and kits for self-sampling for PCR-based HPV DNA testing. Samples from oncogenic HPV positive women were selected for type-specific DNA load testing by real-time PCR with adjustment for cellularity. Linear or logistic regression models were used to evaluate relationships between viral levels, health and sexual behavior, and longitudinal oncogenic HPV detection. Type-specific viral levels were borderline significantly higher in oncogenic HPV infections that were prevalent versus newly detected (p=0.092), but levels in newly detected infections were higher than in infections re-detected after intercurrent negativity (p<.001). Recent sex partners were not significantly associated with viral levels. Compared to prevalent infections detected intermittently, the likelihood of persistent (OR=4.31,95%CI:2.20–8.45) or single-time (OR=1.32,95%CI:1.03–1.71) detection increased per 1-unit increase in baseline log10 viral load. Viral load differences between re-detected and newly detected infections suggest a portion of new detections were due to new acquisition, although report of recent new sex partners (a potential marker of new infection) was not predictive of viral load; oncogenic HPV infections in mid-adult women with new partners likely represent a mix of new acquisition and reactivation or intermittent detection of previous infection. Intermittent detection was characterized by low viral levels, suggesting that intermittent detection of persisting oncogenic HPV infection may be of limited clinical significance PMID:24136492

Applications of rigid and flexible GRIN-endoscopes

NASA Astrophysics Data System (ADS)

Schenkl, Selma; Ehlers, Alexander; Riemann, Iris; Messerschmidt, Bernhard; Bückle, Rainer; König, Karsten

2007-02-01

Multiphoton autofluorescence imaging became an important technique for minimal invasive examination of cells in biological tissue. Rigid and flexible endoscopes based on gradient index lenses (GRIN-lenses) extend this minimalinvasive technique to deep lying cell layers, inner body and specimens, difficult to access. In the rigid endoscope, a GRIN-lens overcomes the limited depth range, given by the working distance of the microscope objective. The focus of the conventional laser scanning tomography is reproduced tens of millimeters in the specimen under study by the GRIN-lens (diameter 1.8 and 3 μm). We will present images of fluorescent beads, proteins cells and skin tissue, as well as first in vivo measurements on human skin. The autofluorescence signal stems from the endogenous fluorophore elastin and SHG from collagen. The flexible endoscope dispenses completely the need of a microscope next to the specimen of interest. The excitation laser pulses is delivered via a well-characterized photonic crystal fiber and subsequently focused by a newly designed GRIN-lens system. The fluorescence, also transferred by a fiber is detected by a PMT detector. We will show the excellent imaging qualities of a newly developed GRIN-lens system with high-resolution images of proteins, cells and plant tissue and give an out-look on multiphoton endoscopy.

Recent trends in digital human modeling and the concurrent issues that face human modeling approach

NASA Technical Reports Server (NTRS)

Rajulu, Sudhakar; Gonzalez, L. Javier; Margerum, Sarah; Clowers, Kurt; Moreny, Richard; Abercomby, Andrew; Velasquez, Luis

2006-01-01

Tremendous strides have been made in the recent years to digitally represent human beings in computer simulation models ranging from assembly plant maintenance operations to occupants getting in and out of vehicles to action movie scenarios. While some of these tools are being actively pursued by the engineering communities, there is still a lot of work that remains to be done for the newly planned planetary exploration missions. For example, certain unique and several common challenges are seen in developing computer generated suited human models for designing the next generation space vehicle. The purpose of this presentation is to discuss NASA s potential needs for better human models and to show also many of the inherent yet not too obvious pitfalls that still are left unresolved in this new arena of digital human modeling. As part of NASA s Habitability and Human Factors Branch, the Anthropometry and Biomechanics Facility has been engaged in studying the various facets of computer generated human physical performance models; for instance, it has been engaged in utilizing three-dimensional laser scan data along with three dimensional video based motion and reach data to gather suited anthropometric and shape and size information that are not available yet in the form of computer mannequins. Our goal is to bring in new approaches to deal with heavily clothed humans (such as, suited astronauts) and to overcome the current limitations of wrongly identifying humans (either real or virtual) as univariate percentiles. We are looking at whole-body posture based anthropometric models as a means to identify humans of significantly different shapes and sizes to arrive at mathematically sound computer models for analytical purposes.

Analysis of the entire genomes of torque teno midi virus variants in chimpanzees: infrequent cross-species infection between humans and chimpanzees.

PubMed

Ninomiya, Masashi; Takahashi, Masaharu; Hoshino, Yu; Ichiyama, Koji; Simmonds, Peter; Okamoto, Hiroaki

2009-02-01

Humans are frequently infected with three anelloviruses which have circular DNA genomes of 3.6-3.9 kb [Torque teno virus (TTV)], 2.8-2.9 kb [Torque teno mini virus (TTMV)] and 3.2 kb [a recently discovered anellovirus named Torque teno midi virus (TTMDV)]. Unexpectedly, human TTMDV DNA was not detectable in any of 74 chimpanzees tested, although all but one tested positive for both human TTV and TTMV DNA. Using universal primers for anelloviruses, novel variants of TTMDV that are phylogenetically clearly separate from human TTMDV were identified from chimpanzees, and over the entire genome, three chimpanzee TTMDV variants differed by 17.9-20.3 % from each other and by 40.4-43.6 % from all 18 reported human TTMDVs. A newly developed PCR assay that uses chimpanzee TTMDV-specific primers revealed the high prevalence of chimpanzee TTMDV in chimpanzees (63/74, 85 %) but low prevalence in humans (1/100). While variants of TTV and TTMV from chimpanzees and humans were phylogenetically interspersed, those of TTMDV were monophyletic for each species, with sequence diversity of <33 and <20 % within the 18 human and three chimpanzee TTMDV variants, respectively. Maximum within-group divergence values for TTV and TTMV were 51 and 57 %, respectively; both of these values were substantially greater than the maximum divergence among TTMDV variants (44 %), consistent with a later evolutionary emergence of TTMDV. However, substantiation of this hypothesis will require further analysis of genetic diversity using an expanded dataset of TTMDV variants in humans and chimpanzees. Similarly, the underlying mechanism of observed infrequent cross-species infection of TTMDV between humans and chimpanzees deserves further analysis.

Part-1: Design, synthesis and biological evaluation of novel bromo-pyrimidine analogs as tyrosine kinase inhibitors.

PubMed

Munikrishnappa, Chandrashekar Suradhenupura; Puranik, Sangamesh B; Kumar, G V Suresh; Prasad, Y Rajendra

2016-08-25

A novel series of 5-bromo-pyrimidine derivatives (5a-l, 6a-h, 9a-m and 10a-d) were synthesized through multi step reactions starting from 5-bromo-2,4-dichloro pyrimidine. The newly synthesized compounds were characterized using elemental analysis and spectral data (IR, (1)H NMR, (13)C NMR and LC-MS) analysis. The titled compounds were evaluated for their in vitro cytotoxic activity against tumor cell lines panel consisted of HCT116 (human colon cancer cell line), A549 (human lung cancer cell line), K562 (human chronic myeloid leukemia cell line), U937 (human acute monocytic myeloid leukemia cell line), and L02 (human normal cell line) by using MTT assay Mosmann's method. As most of the compounds are highly potent against K562 cells, all the synthesized compounds were evaluated for Bcr/Abl tyrosine kinase inhibitory activity by using well-established ADP-Glo assay method. Dasatinib was utilized as positive control to validate in both biological evaluations. The biological activity revealed that the compounds 5c, 5e, 6g, 9e, 9f and 10c were potent Bcr/Abl kinase inhibitors among the titled compounds. Thus these compounds may be promising lead compounds to be developed as an alternative for current Dasatinib therapy. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Rapamycin inhibits anal carcinogenesis in two preclinical animal models.

PubMed

Stelzer, Marie K; Pitot, Henry C; Liem, Amy; Lee, Denis; Kennedy, Gregory D; Lambert, Paul F

2010-12-01

The incidence of anal cancer is increasing especially among HIV-infected persons in the HAART era. Treatment of this cancer is based upon traditional chemoradiotherapeutic approaches, which are associated with high morbidity and of limited effectiveness for patients with high-grade disease. The mammalian target of rapamycin (mTOR) pathway has been implicated in several human cancers, and is being investigated as a potential therapeutic target. In archival human anal cancers, we observed mTOR pathway activation. To assess response of anal cancer to mTOR inhibition, we utilized two newly developed mouse models, one in which anal cancers are induced to arise in HPV16 transgenic mice and the second a human anal cancer xenograft model. Using the transgenic mouse model, we assessed the preventative effect of rapamycin on neoplastic disease. We saw significant changes in the overall incidence of tumors, and tumor growth rate was also reduced. Using both the transgenic mouse and human anal xenograft mouse models, we studied the therapeutic effect of rapamycin on preexisting anal cancer. Rapamycin was found to significantly slow, if not stop, the growth of both mouse and human anal cancers. As has been seen in other cancers, rapamycin treatment led to an activation of the MAPK pathway. These results provide us cause to pursue further the evaluation of rapamycin as a therapeutic agent in the control of anal cancer. ©2010 AACR.

Prevalence of hepatitis C virus and human immunodeficiency virus in a group of patients newly diagnosed with active tuberculosis in Porto Alegre, Southern Brazil.

PubMed

Costi, Cintia; Grandi, Tarciana; Halon, Maria Laura; Silva, Márcia Susana Nunes; Silva, Cláudia Maria Dornelles da; Gregianini, Tatiana Schäffer; Possuelo, Lia Gonçalves; Jarczewski, Carla Adriane; Niel, Christian; Rossetti, Maria Lucia Rosa

2017-04-01

Porto Alegre is the Brazilian state capital with second highest incidence of tuberculosis (TB) and the highest proportion of people infected with human immunodeficiency virus (HIV) among patients with TB. Hepatitis C virus (HCV) infection increases the risk of anti-TB drug-induced hepatotoxicity, which may result in discontinuation of the therapy. The aim of this study was (i) to estimate prevalence of HCV and HIV in a group of patients newly diagnosed with active TB in a public reference hospital in Porto Alegre and (ii) to compare demographic, behavioural, and clinical characteristics of patients in relation to their HCV infection status. One hundred and thirty-eight patients with TB were tested for anti-HCV antibody, HCV RNA, and anti-HIV1/2 antibody markers. HCV RNA from real-time polymerase chain reaction (PCR)-positive samples was submitted to reverse transcription and PCR amplification. The 5' non-coding region of the HCV genome was sequenced, and genotypes of HCV isolates were determined. Anti-HCV antibody, HCV RNA, and anti-HIV antibodies were detected in 27 [20%; 95% confidence interval (CI), 13-26%], 17 (12%; 95% CI, 7-18%), and 34 (25%; 95% CI, 17-32%) patients, respectively. HCV isolates belonged to genotypes 1 (n = 12) and 3 (n = 4). Some characteristics were significantly more frequent in patients infected with HCV. Among them, non-white individuals, alcoholics, users of illicit drugs, imprisoned individuals, and those with history of previous TB episode were more commonly infected with HCV (p < 0.05). HCV screening, including detection of anti-HCV antibody and HCV RNA, will be important to improving the management of co-infected patients, given their increased risk of developing TB treatment-related hepatotoxicity.

Newly generated heparanase knock-out mice unravel co-regulation of heparanase and matrix metalloproteinases.

PubMed

Zcharia, Eyal; Jia, Juan; Zhang, Xiao; Baraz, Lea; Lindahl, Ulf; Peretz, Tamar; Vlodavsky, Israel; Li, Jin-Ping

2009-01-01

Heparanase, a mammalian endo-beta-D-glucuronidase, specifically degrades heparan sulfate proteoglycans ubiquitously associated with the cell surface and extracellular matrix. This single gene encoded enzyme is over-expressed in most human cancers, promoting tumor metastasis and angiogenesis. We report that targeted disruption of the murine heparanase gene eliminated heparanase enzymatic activity, resulting in accumulation of long heparan sulfate chains. Unexpectedly, the heparanase knockout (Hpse-KO) mice were fertile, exhibited a normal life span and did not show prominent pathological alterations. The lack of major abnormalities is attributed to a marked elevation in the expression of matrix metalloproteinases, for example, MMP2 and MMP14 in the Hpse-KO liver and kidney. Co-regulation of heparanase and MMPs was also noted by a marked decrease in MMP (primarily MMP-2,-9 and 14) expression following transfection and over-expression of the heparanase gene in cultured human mammary carcinoma (MDA-MB-231) cells. Immunostaining (kidney tissue) and chromatin immunoprecipitation (ChIP) analysis (Hpse-KO mouse embryonic fibroblasts) suggest that the newly discovered co-regulation of heparanase and MMPs is mediated by stabilization and transcriptional activity of beta-catenin. The lack of heparanase expression and activity was accompanied by alterations in the expression level of MMP family members, primarily MMP-2 and MMP-14. It is conceivable that MMP-2 and MMP-14, which exert some of the effects elicited by heparanase (i.e., over branching of mammary glands, enhanced angiogenic response) can compensate for its absence, in spite of their different enzymatic substrate. Generation of viable Hpse-KO mice lacking significant abnormalities may provide a promising indication for the use of heparanase as a target for drug development.

Minority Human Immunodeficiency Virus Type 1 Variants in Antiretroviral-Naive Persons with Reverse Transcriptase Codon 215 Revertant Mutations▿ †

PubMed Central

Mitsuya, Yumi; Varghese, Vici; Wang, Chunlin; Liu, Tommy F.; Holmes, Susan P.; Jayakumar, Prerana; Gharizadeh, Baback; Ronaghi, Mostafa; Klein, Daniel; Fessel, W. Jeffrey; Shafer, Robert W.

2008-01-01

T215 revertant mutations such as T215C/D/E/S that evolve from the nucleoside reverse transcriptase (RT) inhibitor mutations T215Y/F have been found in about 3% of human immunodeficiency virus type 1 (HIV-1) isolates from newly diagnosed HIV-1-infected persons. We used a newly developed sequencing method—ultradeep pyrosequencing (UDPS; 454 Life Sciences)—to determine the frequency with which T215Y/F or other RT inhibitor resistance mutations could be detected as minority variants in samples from untreated persons that contain T215 revertants (“revertant” samples) compared with samples from untreated persons that lack such revertants (“control” samples). Among the 22 revertant and 29 control samples, UDPS detected a mean of 3.8 and 4.8 additional RT amino acid mutations, respectively. In 6 of 22 (27%) revertant samples and in 4 of 29 control samples (14%; P = 0.4), UDPS detected one or more RT inhibitor resistance mutations. T215Y or T215F was not detected in any of the revertant or control samples; however, 4 of 22 revertant samples had one or more T215 revertants that were detected by UDPS but not by direct PCR sequencing. The failure to detect viruses with T215Y/F in the 22 revertant samples in this study may result from the overwhelming replacement of transmitted T215Y variants by the more fit T215 revertants or from the primary transmission of a T215 revertant in a subset of persons with T215 revertants. PMID:18715933

Single-cell systems level analysis of human Toll-Like-Receptor activation defines a chemokine signature in Systemic Lupus Erythematosus

PubMed Central

O'Gorman, William E.; Hsieh, Elena W.Y.; Savig, Erica S.; Gherardini, Pier Federico; Hernandez, Joseph D.; Hansmann, Leo; Balboni, Imelda M.; Utz, Paul J.; Bendall, Sean C.; Fantl, Wendy J.; Lewis, David B.; Nolan, Garry P.; Davis, Mark M.

2015-01-01

Background Activation of Toll-Like Receptors (TLRs) induces inflammatory responses involved in immunity to pathogens and autoimmune pathogenesis, such as in Systemic Lupus Erythematosus (SLE). Although TLRs are differentially expressed across the immune system, a comprehensive analysis of how multiple immune cell subsets respond in a system-wide manner has previously not been described. Objective To characterize TLR activation across multiple immune cell subsets and individuals, with the goal of establishing a reference framework against which to compare pathological processes. Methods Peripheral whole blood samples were stimulated with TLR ligands, and analyzed by mass cytometry simultaneously for surface marker expression, activation states of intracellular signaling proteins, and cytokine production. We developed a novel data visualization tool to provide an integrated view of TLR signaling networks with single-cell resolution. We studied seventeen healthy volunteer donors and eight newly diagnosed untreated SLE patients. Results Our data revealed the diversity of TLR-induced responses within cell types, with TLR ligand specificity. Subsets of NK and T cells selectively induced NF-κB in response to TLR2 ligands. CD14hi monocytes exhibited the most polyfunctional cytokine expression patterns, with over 80 distinct cytokine combinations. Monocytic TLR-induced cytokine patterns were shared amongst a group of healthy donors, with minimal intra- and inter- individual variability. Furthermore, autoimmune disease altered baseline cytokine production, as newly diagnosed untreated SLE patients shared a distinct monocytic chemokine signature, despite clinical heterogeneity. Conclusion Mass cytometry analysis defined a systems-level reference framework for human TLR activation, which can be applied to study perturbations in inflammatory disease, such as SLE. PMID:26037552

Shifting diets and the rise of male-biased inequality on the Central Plains of China during Eastern Zhou.

PubMed

Dong, Yu; Morgan, Chelsea; Chinenov, Yurii; Zhou, Ligang; Fan, Wenquan; Ma, Xiaolin; Pechenkina, Kate

2017-01-31

Farming domesticated millets, tending pigs, and hunting constituted the core of human subsistence strategies during Neolithic Yangshao (5000-2900 BC). Introduction of wheat and barley as well as the addition of domesticated herbivores during the Late Neolithic (∼2600-1900 BC) led to restructuring of ancient Chinese subsistence strategies. This study documents a dietary shift from indigenous millets to the newly introduced cereals in northcentral China during the Bronze Age Eastern Zhou Dynasty (771-221 BC) based on stable isotope analysis of human and animal bone samples. Our results show that this change affected females to a greater degree than males. We find that consumption of the newly introduced cereals was associated with less consumption of animal products and a higher rate of skeletal stress markers among females. We hypothesized that the observed separation of dietary signatures between males and females marks the rise of male-biased inequality in early China. We test this hypothesis by comparing Eastern Zhou human skeletal data with those from Neolithic Yangshao archaeological contexts. We find no evidence of male-female inequality in early farming communities. The presence of male-biased inequality in Eastern Zhou society is supported by increased body height difference between the sexes as well as the greater wealth of male burials.

Stressors of newly graduated nurses in Shanghai paediatric hospital: a qualitative study.

PubMed

Hu, Yun; Zhang, Yaqing; Shen, Nanping; Wu, Juemin; Wu, Jia; Malmedal, Wenche K

2017-04-01

To identify stressors of newly graduated paediatric nurses at a children's hospital in Shanghai, China. Stress is an international phenomenon in nursing generally, but little is known about its effect on new paediatric nurses at the Shanghai paediatric hospital. Participants in this research were 25 newly graduated paediatric nurses. Their behaviours and perceptions were explored by field observations and interviews. Findings indicated that participants experienced numerous stressors: low work status, insufficient professional competence, heavy workload, inadequate supportive systems and uncertainty of career development. The results of the present study provide useful information for administrators to develop and improve postgraduate programmes to support novice paediatric nurses. Our research highlights the importance of identifying the stressors of new paediatric nurses in the light of a serious nurse shortage and an increasing birth rate. © 2016 John Wiley & Sons Ltd.

Merkel Cell Polyomavirus: A Newly Discovered Human Virus with Oncogenic Potential

PubMed Central

Spurgeon, Megan E.; Lambert, Paul F.

2012-01-01

A marked escalation in the rate of discovery of new types of human polyomavirus has occurred over the last five years largely owing to recent technological advances in their detection. Among the newly discovered viruses, Merkel Cell Polyomavirus (MCPyV or MCV) has gained the most attention due to its link with a rare human cancer. Infection with MCPyV is common in the human population, and the virus is detected in several anatomical locations, but most frequently in skin. Study of MCPyV molecular virology has been complicated by the lack of straightforward cell culture models, but recent in vitro studies are making strides towards understanding the virus life cycle, its cellular tropism, and mode of transmission. While MCPyV shares several traditional traits with other human polyomaviruses, the burst of research since its discovery reveals insight into a virus with many unique genetic and mechanistic features. The evidence for a causal link between MCPyV and the rare neuroendocrine cancer, Merkel Cell Carcinoma (MCC), is compelling. A majority of MCCs contain clonally integrated viral DNA, express viral T antigen transcripts and protein, and exhibit an addiction to the viral large T and small t antigen oncoproteins. The MCPyV large T antigen contains MCC tumor-specific mutations that ablate its replication capacity but preserve its oncogenic functions, and the small t antigen promotes an environment favorable for cap-dependent translation. The mechanisms of MCPyV-induced transformation have not been fully elucidated, but the likely etiological role of this new polyomavirus in human cancer provides a strong opportunity to expand knowledge of virus-host interactions and viral oncology. PMID:23217622

Insulin Transactivator MafA Regulates Intrathymic Expression of Insulin and Affects Susceptibility to Type 1 Diabetes

PubMed Central

Noso, Shinsuke; Kataoka, Kohsuke; Kawabata, Yumiko; Babaya, Naru; Hiromine, Yoshihisa; Yamaji, Kaori; Fujisawa, Tomomi; Aramata, Shinsaku; Kudo, Takashi; Takahashi, Satoru; Ikegami, Hiroshi

2010-01-01

OBJECTIVE Tissue-specific self-antigens are ectopically expressed within the thymus and play an important role in the induction of central tolerance. Insulin is expressed in both pancreatic islets and the thymus and is considered to be the primary antigen for type 1 diabetes. Here, we report the role of the insulin transactivator MafA in the expression of insulin in the thymus and susceptibility to type 1 diabetes. RESEARCH DESIGN AND METHODS The expression profiles of transcriptional factors (Pdx1, NeuroD, Mafa, and Aire) in pancreatic islets and the thymus were examined in nonobese diabetic (NOD) and control mice. Thymic Ins2 expression and serum autoantibodies were examined in Mafa knockout mice. Luciferase reporter assay was performed for newly identified polymorphisms of mouse Mafa and human MAFA. A case-control study was applied for human MAFA polymorphisms. RESULTS Mafa, Ins2, and Aire expression was detected in the thymus. Mafa expression was lower in NOD thymus than in the control and was correlated with Ins2 expression. Targeted disruption of MafA reduced thymic Ins2 expression and induced autoantibodies against pancreatic islets. Functional polymorphisms of MafA were newly identified in NOD mice and humans, and polymorphisms of human MAFA were associated with susceptibility to type 1 diabetes but not to autoimmune thyroid disease. CONCLUSIONS These data indicate that functional polymorphisms of MafA are associated with reduced expression of insulin in the thymus and susceptibility to type 1 diabetes in the NOD mouse as well as human type 1 diabetes. PMID:20682694

Self-Esteem: A Comparison between Hong Kong Children and Newly Arrived Chinese Children

ERIC Educational Resources Information Center

Chan, Yiu Man; Chan, Christine Mei-Sheung

2004-01-01

The Self-esteem Inventory developed by Coopersmith (1967) was used to measure the self-esteem of 387 Chinese children. The sample included newly arrived mainland Chinese children and Hong Kong children. The results showed significant statistical differences when measuring the self-esteem level associated with the length of their stay in Hong Kong…

Identifying the Training Needs of Heads of Department in a Newly Established University in Vietnam

ERIC Educational Resources Information Center

Nguyen, Thi Lan Huong

2012-01-01

Although middle-level academic managers really need training in order to perform their roles adequately in the very changing context of higher education, little formal training is provided, particularly in less developed countries. This paper identifies the training needs of Heads of Department in a newly established university in Vietnam as a…

Course and Prognosis of Childhood Epilepsy: 5-Year Follow-Up of the Dutch Study of Epilepsy in Childhood

ERIC Educational Resources Information Center

Arts, Willem F. M.; Brouwer, Oebele F.; Peters, A. C. Boudewijn; Stroink, Hans; Peeters, Els A. J.; Schmitz, Paul I. M.; van Donselaar, Cees A.; Geerts, Ada T.

2004-01-01

Knowing the prognosis of epilepsy will undoubtedly influence the treatment strategy. This study aimed to define the prospects of newly diagnosed childhood epilepsy, assess the dynamics of its course, identify relevant variables and develop models to assess the individual prognosis. Four hundred and fifty-three children with newly diagnosed…

Evaluating the Acceptability and Feasibility of Project ACCEPT: An Intervention for Youth Newly Diagnosed with HIV

ERIC Educational Resources Information Center

Hosek, Sybil G.; Lemos, Diana; Harper, Gary W.; Telander, Kyle

2011-01-01

Given the potential for negative psychosocial and medical outcomes following an HIV diagnosis, Project ACCEPT, a 12-session behavioral intervention, was developed and pilot-tested for youth (aged 16-24) newly diagnosed with HIV. Fifty participants recently diagnosed with HIV were enrolled from 4 sites selected through the Adolescent Medicine…

Phenology of Lymantria monacha (Lepidoptera:Lymantriidae) laboratory reared on spruce foliage or a newly developed artificial diet

Treesearch

Melody A. Keena; Alice Vandel; Oldrich. Pultar

2010-01-01

Lymantria monacha (L.) (Lepidoptera: Lymantriidae) is a Eurasian pest of conifers that has potential for accidental introduction into North America. The phenology over the entire life cycle for L. monacha individuals from the Czech Republic was compared on Picea glauca (Moench) Voss (white spruce) and a newly...

Comparison of a new multiplex real-time PCR with the Kato Katz thick smear and copro-antigen ELISA for the detection and differentiation of Taenia spp. in human stools.

PubMed

Ng-Nguyen, Dinh; Stevenson, Mark A; Dorny, Pierre; Gabriël, Sarah; Vo, Tinh Van; Nguyen, Van-Anh Thi; Phan, Trong Van; Hii, Sze Fui; Traub, Rebecca J

2017-07-01

Taenia solium, the cause of neurocysticercosis (NCC), has significant socioeconomic impacts on communities in developing countries. This disease, along with taeniasis is estimated to infect 2.5 to 5 million people globally. Control of T. solium NCC necessitates accurate diagnosis and treatment of T. solium taeniasis carriers. In areas where all three species of Taenia tapeworms (T. solium, Taenia saginata and Taenia asiatica) occur sympatrically, conventional microscope- and copro-antigen based diagnostic methods are unable to distinguish between these three Taenia species. Molecular diagnostic tools have been developed to overcome this limitation; however, conventional PCR-based techniques remain unsuitable for large-scale deployment in community-based surveys. Moreover, a real-time PCR (qPCR) for the discrimination of all three species of Taenia in human stool does not exist. This study describes the development and validation of a new triplex Taq-Man probe-based qPCR for the detection and discrimination of all three Taenia human tapeworms in human stools collected from communities in the Central Highlands of Vietnam. The diagnostic characteristics of the test are compared with conventional Kato Katz (KK) thick smear and copro-antigen ELISA (cAgELISA) method utilizing fecal samples from a community based cross-sectional study. Using this new multiplex real-time PCR we provide an estimate of the true prevalence of taeniasis in the source population for the community based cross-sectional study. Primers and TaqMan probes for the specific amplification of T. solium, T. saginata and T. asiatica were designed and successfully optimized to target the internal transcribed spacer I (ITS-1) gene of T. solium and the cytochrome oxidase subunit I (COX-1) gene of T. saginata and T. asiatica. The newly designed triplex qPCR (T3qPCR) was compared to KK and cAgELISA for the detection of Taenia eggs in stool samples collected from 342 individuals in Dak Lak province, Central Highlands of Vietnam. The overall apparent prevalence of taeniasis in Dak Lak province was 6.72% (95% confidence interval (CI) [3.94-9.50]) in which T. solium accounted for 1.17% (95% CI [0.37-3.17]), according to the T3qPCR. There was sympatric presence of T. solium, T. saginata and T. asiatica. The T3qPCR proved superior to KK and cAgELISA for the detection and differentiation of Taenia species in human feces. Diagnostic sensitivities of 0.94 (95% credible interval (CrI) [0.88-0.98]), 0.82 (95% CrI [0.58-0.95]) and 0.52 (95% CrI [0.07-0.94]), and diagnostic specificities of 0.98 (95% CrI [0.94-1.00]), 0.91 (95% CrI [0.85-0.96]) and 0.99 (95% CrI [0.96-1.00]) were estimated for the diagnosis of taeniasis for the T3qPCR, cAgELISA and KK thick smear in this study, respectively. T3qPCR is not only superior to the KK thick smear and cAgELISA in terms of diagnostic sensitivity and specificity, but it also has the advantage of discriminating between species of Taenia eggs in stools. Application of this newly developed T3qPCR has identified the existence of all three human Taenia tapeworms in Dak Lak province and proves for the first time, the existence of T. asiatica in the Central Highlands and the south of Vietnam.

The risk of newly developed visual impairment in treated normal-tension glaucoma: 10-year follow-up.

PubMed

Choi, Yun Jeong; Kim, Martha; Park, Ki Ho; Kim, Dong Myung; Kim, Seok Hwan

2014-12-01

To investigate the risk and risk factors for newly developed visual impairment in treated patients with normal-tension glaucoma (NTG) followed up on for 10 years. Patients with NTG, who did not have visual impairment at the initial diagnosis and had undergone intraocular pressure (IOP)-lowering treatment for more than 7 years, were included on the basis of a retrospective chart review. Visual impairment was defined as either low vision (0.05 [20/400] ≤ visual acuity (VA) <0.3 [20/60] and/or 10 degrees ≤ central visual field (VF) <20 degrees) or blindness (VA <0.05 [20/400] and/or central VF <10 degrees) by World Health Organization (WHO) criteria. To investigate the risk and risk factors for newly developed visual impairment, Kaplan-Meier survival analysis and generalized linear mixed effects models were utilized. During the 10.8 years mean follow-up period, 20 eyes of 16 patients were diagnosed as visual impairment (12 eyes as low vision, 8 as blindness) among 623 eyes of 411 patients. The cumulative risk of visual impairment in at least one eye was 2.8% at 10 years and 8.7% at 15 years. The risk factors for visual impairment from treated NTG were worse VF mean deviation (MD) at diagnosis and longer follow-up period. The risk of newly developed visual impairment in the treated patients with NTG was relatively low. Worse VF MD at diagnosis and longer follow-up period were associated with development of visual impairment. © 2014 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Restoration of the intrinsic properties of human dermal papilla in vitro.

PubMed

Ohyama, Manabu; Kobayashi, Tetsuro; Sasaki, Takashi; Shimizu, Atsushi; Amagai, Masayuki

2012-09-01

The dermal papilla (DP) plays pivotal roles in hair follicle morphogenesis and cycling. However, characterization and/or propagation of human DPs have been unsatisfactory because of the lack of efficient isolation methods and the loss of innate characteristics in vitro. We hypothesized that culture conditions sustaining the intrinsic molecular signature of the human DP could facilitate expansion of functional DP cells. To test this, we first characterized the global gene expression profile of microdissected, non-cultured human DPs. We performed a 'two-step' microarray analysis to exclude the influence of unwanted contaminants in isolated DPs and successfully identified 118 human DP signature genes, including 38 genes listed in the mouse DP signature. The bioinformatics analysis of the DP gene list revealed that WNT, BMP and FGF signaling pathways were upregulated in intact DPs and addition of 6-bromoindirubin-3'-oxime, recombinant BMP2 and basic FGF to stimulate these respective signaling pathways resulted in maintained expression of in situ DP signature genes in primarily cultured human DP cells. More importantly, the exposure to these stimulants restored normally reduced DP biomarker expression in conventionally cultured DP cells. Cell growth was moderate in the newly developed culture medium. However, rapid DP cell expansion by conventional culture followed by the restoration by defined activators provided a sufficient number of DP cells that demonstrated characteristic DP activities in functional assays. The study reported here revealed previously unreported molecular mechanisms contributing to human DP properties and describes a useful technique for the investigation of human DP biology and hair follicle bioengineering.

Human Ageing Genomic Resources: Integrated databases and tools for the biology and genetics of ageing

PubMed Central

Tacutu, Robi; Craig, Thomas; Budovsky, Arie; Wuttke, Daniel; Lehmann, Gilad; Taranukha, Dmitri; Costa, Joana; Fraifeld, Vadim E.; de Magalhães, João Pedro

2013-01-01

The Human Ageing Genomic Resources (HAGR, http://genomics.senescence.info) is a freely available online collection of research databases and tools for the biology and genetics of ageing. HAGR features now several databases with high-quality manually curated data: (i) GenAge, a database of genes associated with ageing in humans and model organisms; (ii) AnAge, an extensive collection of longevity records and complementary traits for >4000 vertebrate species; and (iii) GenDR, a newly incorporated database, containing both gene mutations that interfere with dietary restriction-mediated lifespan extension and consistent gene expression changes induced by dietary restriction. Since its creation about 10 years ago, major efforts have been undertaken to maintain the quality of data in HAGR, while further continuing to develop, improve and extend it. This article briefly describes the content of HAGR and details the major updates since its previous publications, in terms of both structure and content. The completely redesigned interface, more intuitive and more integrative of HAGR resources, is also presented. Altogether, we hope that through its improvements, the current version of HAGR will continue to provide users with the most comprehensive and accessible resources available today in the field of biogerontology. PMID:23193293

The human retrovirus XMRV in prostate cancer and chronic fatigue syndrome.

PubMed

Silverman, Robert H; Nguyen, Carvell; Weight, Christopher J; Klein, Eric A

2010-07-01

Xenotropic murine leukemia virus-related virus (XMRV) is an authentic, newly recognized human retrovirus first identified in prostate cancer tissues from men with a deficiency in the innate immunity gene RNASEL. At present, studies have detected XMRV at widely different rates in prostate cancer cases (0-27%) and in patients with chronic fatigue syndrome (CFS; 0-67%). Indirect or direct modes of carcinogenesis by XMRV have been suggested depending on whether the virus was found in stroma or malignant epithelium. Viral replication in the prostate might be affected by androgens, which stimulate XMRV through a transcriptional enhancer site in viral DNA. By contrast, host restriction factors, such as APOBEC3 and tetherin, inhibit virus replication. Immune dysfunction mediated by XMRV has been suggested as a possible factor in CFS. Recent studies show that some existing antiretroviral drugs suppress XMRV infections and diagnostic assays are under development. Although other retroviruses of the same genus as XMRV (gammaretroviruses) cause cancer and neurological disease in animals, whether XMRV is a cause of either prostate cancer or CFS remains unknown. Emerging science surrounding XMRV is contributing to our knowledge of retroviral infections while focusing intense interest on two major human diseases.

Three-dimensional culture and differentiation of human osteogenic cells in an injectable hydroxypropylmethylcellulose hydrogel.

PubMed

Trojani, Christophe; Weiss, Pierre; Michiels, Jean-François; Vinatier, Claire; Guicheux, Jérôme; Daculsi, Guy; Gaudray, Patrick; Carle, Georges F; Rochet, Nathalie

2005-09-01

The present work evaluates a newly developed silated hydroxypropylmethylcellulose (Si-HPMC)-based hydrogel as a scaffold for 3D culture of osteogenic cells. The pH variation at room temperature catalyzes the reticulation and self-hardening of the viscous polymer solution into a gelatine state. We designed reticulation time, final consistency and pH in order to obtain an easy handling matrice, suitable for in vitro culture and in vivo injection. Three human osteogenic cell lines and normal human osteogenic (HOST) cells were cultured in 3D inside this Si-HPMC hydrogel. We show here that osteosarcoma cells proliferate as clonogenic spheroids and that HOST colonies survive for at least 3 weeks. Mineralization assay and gene expression analysis of osteoblastic markers and cytokines, indicate that all the cells cultured in 3D into this hydrogel, exhibited a more mature differentiation status than cells cultured in monolayer on plastic. This study demonstrates that this Si-HPMC hydrogel is well suited to support osteoblastic survival, proliferation and differentiation when used as a new scaffold for 3D culture and represents also a potential basis for an innovative bone repair material.

Hierarchical regulation of the genome: global changes in nucleosome organization potentiate genome response

PubMed Central

Sexton, Brittany S.; Druliner, Brooke R.; Vera, Daniel L.; Avey, Denis; Zhu, Fanxiu; Dennis, Jonathan H.

2016-01-01

Nucleosome occupancy is critically important in regulating access to the eukaryotic genome. Few studies in human cells have measured genome-wide nucleosome distributions at high temporal resolution during a response to a common stimulus. We measured nucleosome distributions at high temporal resolution following Kaposi's-sarcoma-associated herpesvirus (KSHV) reactivation using our newly developed mTSS-seq technology, which maps nucleosome distribution at the transcription start sites (TSS) of all human genes. Nucleosomes underwent widespread changes in organization 24 hours after KSHV reactivation and returned to their basal nucleosomal architecture 48 hours after KSHV reactivation. The widespread changes consisted of an indiscriminate remodeling event resulting in the loss of nucleosome rotational phasing signals. Additionally, one in six TSSs in the human genome possessed nucleosomes that are translationally remodeled. 72% of the loci with translationally remodeled nucleosomes have nucleosomes that moved to positions encoded by the underlying DNA sequence. Finally we demonstrated that these widespread alterations in nucleosomal architecture potentiated regulatory factor binding. These descriptions of nucleosomal architecture changes provide a new framework for understanding the role of chromatin in the genomic response, and have allowed us to propose a hierarchical model for chromatin-based regulation of genome response. PMID:26771136

Zymographic analysis using gelatin-coated film of the effect of etanercept on the extracellular matrix-degrading activity in synovial fluids of rheumatoid arthritis patients.

PubMed

Kamataki, Akihisa; Ishida, Mutsuko; Komagamine, Masataka; Yoshida, Masaaki; Ando, Takanobu; Sawai, Takashi

2016-04-01

Rheumatoid arthritis (RA) is a chronic inflammatory disease. Most RA patients develop cartilage and bone destruction, and various proteinases are involved in the destruction of extracellular matrix of cartilage and bone. The aim of this study is to evaluate the utility of our newly developed method to measure total gelatinolytic activity. We adopted this method for measurement in synovial fluid from RA patients treated by the anti-rheumatic drug etanercept (ETN), a recombinant human soluble tumor necrosis factor receptor fusion protein, and compared the findings with clinical and laboratory data. Enzymatic activity of synovial fluid was analyzed by zymography using gelatin-coated film, and compared with the index of Disease Activity Score of 28 joints - C-reactive protein (DAS28-CRP), CRP and matrix metalloproteinase (MMP)-3 level before and after ETN therapy. Synovial fluids of 19 patients were collected before and after administration of ETN therapy. In nine of 19 patients, who showed a decrease in gelatin-degrading activity in synovial fluid, the index of DAS28-CRP (4.85-2.85, ΔDAS = -2.00) and CRP (3.30-0.94 mg/dL, ΔCRP = -2.36) was alleviated after ETN therapy, while cases with no change or an increase in gelatin-degrading activity showed a modest improvement in clinical data: DAS28-CRP (4.23-3.38, ΔDAS = -0.85) and CRP (1.70-0.74 mg/dL, ΔCRP = -0.96). Our newly developed method for measurement of gelatin-degrading activity in synovial fluid from RA patients is highly practicable and useful for predicting the effect of ETN therapy. © 2013 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

Anti-Cancer Properties of a Novel Class of Tetrafluorinated Thalidomide Analogs

PubMed Central

Beedie, Shaunna L.; Peer, Cody J.; Pisle, Steven; Gardner, Erin R.; Mahony, Chris; Barnett, Shelby; Ambrozak, Agnieszka; Gütschow, Michael; Chau, Cindy H.; Vargesson, Neil; Figg, William D.

2015-01-01

Thalidomide has demonstrated clinical activity in various malignancies affecting immunomodulatory and angiogenesis pathways. The development of novel thalidomide analogs with improved efficacy and decreased toxicity is an ongoing research effort. We recently designed and synthesized a new class of compounds, consisting of both tetrafluorinated thalidomide analogs (Gu973 and Gu998) and tetrafluorobenzamides (Gu1029 and Gu992). In this study, we demonstrate the anti-angiogenic properties of these newly synthesized compounds. We examined the specific anti-angiogenic characteristics in vitro using rat aortic rings with carboxyamidotriazole as a positive control. Additionally, further in vitro efficacy was evaluated using HUVECs and PC3 cells treated with 5μM and 10μM doses of each compound. All compounds were seen to reduce microvessel outgrowth in rat aortic rings as well as inhibit HUVECs to a greater extent, at lower concentrations than previously tested thalidomide analogs. The anti-angiogenic properties of the compounds was also examined in vivo in fli1:EGFP zebrafish embryos, where all compounds were seen to inhibit the extent of outgrowth of newly developing blood vessels. In addition, Gu1029 and Gu973 reduced the anti-inflammatory response in mpo:GFP zebrafish embryos, while Gu998 and Gu992 showed no difference. The compounds anti-tumor effects were also explored in vivo using the human prostate cancer PC3 xenograft model. All four compounds were also screened in vivo in chicken embryos to investigate their teratogenic potential. This study establishes these novel thalidomide analogs as a promising immunomodulatory class with anti-cancer effects that warrant further development to characterize their mechanisms of action. PMID:26269604

Evaluation of inapparent nosocomial severe acute respiratory syndrome coronavirus infection in Vietnam by use of highly specific recombinant truncated nucleocapsid protein-based enzyme-linked immunosorbent assay.

PubMed

Yu, Fuxun; Le, Mai Quynh; Inoue, Shingo; Thai, Hong Thi Cam; Hasebe, Futoshi; Del Carmen Parquet, Maria; Morita, Kouichi

2005-07-01

Severe acute respiratory syndrome (SARS) is a recently emerged human disease associated with pneumonia. Inapparent infection with SARS coronavirus (CoV) is not well characterized. To develop a safe, simple, and reliable screening method for SARS diagnosis and epidemiological study, two recombinant SARS-CoV nucleocapsid proteins (N' protein and (N)Delta(121) protein) were expressed in Escherichia coli, purified by affinity chromatography, and used as antigens for indirect, immunoglobulin G enzyme-linked immunosorbent assays (ELISA). Serum samples collected from healthy volunteers and SARS patients in Vietnam were used to evaluate the newly developed methods. The N' protein-based ELISA showed a highly nonspecific reaction. The (N)Delta(121) protein-based ELISA, with a nonspecific reaction drastically reduced compared to that of the nearly-whole-length N' protein-based ELISA, resulted in higher rates of positive reactions, higher titers, and earlier detection than the SARS-CoV-infected cell lysate-based ELISA. These results indicate that our newly developed SARS-CoV (N)Delta(121) protein-based ELISA is not only safe but also a more specific and more sensitive method to diagnose SARS-CoV infection and hence a useful tool for large-scale epidemiological studies. To identify inapparent SARS-CoV infections, serum samples collected from health care workers (HCWs) in Vietnam were screened by the (N)Delta(121) protein-based ELISA, and positive samples were confirmed by a virus neutralization test. Four out of 149 HCWs were identified to have inapparent SARS-CoV infection in Vietnam, indicating that subclinical SARS-CoV infection in Vietnam is rare but does exist.

Evaluation of Inapparent Nosocomial Severe Acute Respiratory Syndrome Coronavirus Infection in Vietnam by Use of Highly Specific Recombinant Truncated Nucleocapsid Protein-Based Enzyme-Linked Immunosorbent Assay

PubMed Central

Yu, Fuxun; Le, Mai Quynh; Inoue, Shingo; Thai, Hong Thi Cam; Hasebe, Futoshi; del Carmen Parquet, Maria; Morita, Kouichi

2005-01-01

Severe acute respiratory syndrome (SARS) is a recently emerged human disease associated with pneumonia. Inapparent infection with SARS coronavirus (CoV) is not well characterized. To develop a safe, simple, and reliable screening method for SARS diagnosis and epidemiological study, two recombinant SARS-CoV nucleocapsid proteins (N′ protein and NΔ121 protein) were expressed in Escherichia coli, purified by affinity chromatography, and used as antigens for indirect, immunoglobulin G enzyme-linked immunosorbent assays (ELISA). Serum samples collected from healthy volunteers and SARS patients in Vietnam were used to evaluate the newly developed methods. The N′ protein-based ELISA showed a highly nonspecific reaction. The NΔ121 protein-based ELISA, with a nonspecific reaction drastically reduced compared to that of the nearly-whole-length N′ protein-based ELISA, resulted in higher rates of positive reactions, higher titers, and earlier detection than the SARS-CoV-infected cell lysate-based ELISA. These results indicate that our newly developed SARS-CoV NΔ121 protein-based ELISA is not only safe but also a more specific and more sensitive method to diagnose SARS-CoV infection and hence a useful tool for large-scale epidemiological studies. To identify inapparent SARS-CoV infections, serum samples collected from health care workers (HCWs) in Vietnam were screened by the NΔ121 protein-based ELISA, and positive samples were confirmed by a virus neutralization test. Four out of 149 HCWs were identified to have inapparent SARS-CoV infection in Vietnam, indicating that subclinical SARS-CoV infection in Vietnam is rare but does exist. PMID:16002634

Performance evaluation of neuro-PET using silicon photomultipliers

NASA Astrophysics Data System (ADS)

Jung, Jiwoong; Choi, Yong; Jung, Jin Ho; Kim, Sangsu; Im, Ki Chun

2016-05-01

Recently, we have developed the second prototype Silicon photomultiplier (SiPM) based positron emission tomography (PET) scanner for human brain imaging. The PET system was comprised of detector block which consisted of 4×4 SiPMs and 4×4 Lutetium Yttrium Orthosilicate arrays, charge signal transmission method, high density position decoder circuit and FPGA-embedded ADC boards. The purpose of this study was to evaluate the performance of the newly developed neuro-PET system. The energy resolution, timing resolution, spatial resolution, sensitivity, stability of the photo-peak position and count rate performance were measured. Tomographic image of 3D Hoffman brain phantom was also acquired to evaluate imaging capability of the neuro-PET. The average energy and timing resolutions measured for 511 keV gamma rays were 17±0.1% and 3±0.3 ns, respectively. Spatial resolution and sensitivity at the center of field of view (FOV) were 3.1 mm and 0.8%, respectively. The average scatter fraction was 0.4 with an energy window of 350-650 keV. The maximum true count rate and maximum NECR were measured as 43.3 kcps and 6.5 kcps at an activity concentration of 16.7 kBq/ml and 5.5 kBq/ml, respectively. Long-term stability results show that there was no significant change in the photo-peak position, energy resolution and count rate for 60 days. Phantom imaging studies were performed and they demonstrated the feasibility for high quality brain imaging. The performance tests and imaging results indicate that the newly developed PET is useful for brain imaging studies, if the axial FOV is extended to improve the system sensitivity.

Transspinal direct current stimulation modulates migration and proliferation of adult newly born spinal cells in mice.

PubMed

Samaddar, Sreyashi; Vazquez, Kizzy; Ponkia, Dipen; Toruno, Pedro; Sahbani, Karim; Begum, Sultana; Abouelela, Ahmed; Mekhael, Wagdy; Ahmed, Zaghloul

2017-02-01

Direct current electrical fields have been shown to be a major factor in the regulation of cell proliferation, differentiation, migration, and survival, as well as in the maturation of dividing cells during development. During adulthood, spinal cord cells are continuously produced in both animals and humans, and they hold great potential for neural restoration following spinal cord injury. While the effects of direct current electrical fields on adult-born spinal cells cultured ex vivo have recently been reported, the effects of direct current electrical fields on adult-born spinal cells in vivo have not been characterized. Here, we provide convincing findings that a therapeutic form of transspinal direct current stimulation (tsDCS) affects the migration and proliferation of adult-born spinal cells in mice. Specifically, cathodal tsDCS attracted the adult-born spinal cells, while anodal tsDCS repulsed them. In addition, both tsDCS polarities caused a significant increase in cell number. Regarding the potential mechanisms involved, both cathodal and anodal tsDCS caused significant increases in expression of brain-derived neurotrophic factor, while expression of nerve growth factor increased and decreased, respectively. In the spinal cord, both anodal and cathodal tsDCS increased blood flow. Since blood flow and angiogenesis are associated with the proliferation of neural stem cells, increased blood flow may represent a major factor in the modulation of newly born spinal cells by tsDCS. Consequently, we propose that the method and novel findings presented in the current study have the potential to facilitate cellular, molecular, and/or bioengineering strategies to repair injured spinal cords. NEW & NOTEWORTHY Our results indicate that transspinal direct current stimulation (tsDCS) affects the migratory pattern and proliferation of adult newly born spinal cells, a cell population which has been implicated in learning and memory. In addition, our results suggest a potential mechanism of action regarding the functional effects of applying direct current. Thus tsDCS may represent a novel method by which to manipulate the migration and cell number of adult newly born cells and restore functions following brain or spinal cord injury. Copyright © 2017 the American Physiological Society.

Higher levels of physical activity are independently associated with a lower incidence of diabetic retinopathy in Japanese patients with type 2 diabetes: A prospective cohort study, Diabetes Distress and Care Registry at Tenri (DDCRT15).

PubMed

Kuwata, Hirohito; Okamura, Shintaro; Hayashino, Yasuaki; Tsujii, Satoru; Ishii, Hitoshi

2017-01-01

We assessed the prospective association between baseline levels of physical activity (PA) and the incidence of newly developed diabetic retinopathy (DR) in patients with type 2 diabetes. Data from 1,814 patients with type 2 diabetes without DR were obtained from a Japanese diabetes registry at Tenri Hospital, Nara, Japan. To assess the independent correlations between baseline PA levels and newly developed DR, the participants were divided into five categories based on their PA levels. A Cox proportional hazards model with time-varying exposure information was used and adjusted for potential confounders to assess the independent correlations. At baseline, the mean age, BMI, and hemoglobin A1c levels of the patients were 65.5 years, 24.5 kg/m2, and 7.2% (54 mmol/mol), respectively. After 2 years, newly developed DR was confirmed in 184 patients (10.1%). Patients with newly developed DR had longer duration of type 2 diabetes (14.7 versus 11.0 years, p < 0.0001), higher systolic blood pressure (139.2 versus 135.1 mmHg, p = 0.0012), lower estimated glomerular filtration rate (74.0 versus 77.1 mL/min/1.73 m2, p = 0.0382), greater urinary albumin-creatinine ratio (4.00 versus 2.45 mg/mmol, p < 0.0039), and higher HbA1c levels (7.5 versus 7.2%, p = 0.0006) than those without newly developed DR. The multivariable-adjusted hazard ratios for DR development were 0.87 (95% CI, 0.53-1.40; p = 0.557), 0.83 (95% CI, 0.52-1.31; p = 0.421), 0.58 (95% CI, 0.35-0.94; p = 0.027), and 0.63 (95% CI, 0.42-0.94; p = 0.025)for the second, third, fourth, and fifth PA categories, respectively, compared with the reference category of patients with a mean PA of 0 metabolic equivalent of task-hours/week). Higher PA levels are independently associated with a lower incidence of DR in Japanese patients with type 2 diabetes.

Surveillance of Hantaviruses in Poland: A Study of Animal Reservoirs and Human Hantavirus Disease in Subcarpathia

PubMed Central

Niemcewicz, Marcin; Bielawska-Drózd, Agata; Nowakowska, Anna; Gaweł, Jerzy; Pitucha, Grzegorz; Joniec, Justyna; Zielonka, Katarzyna; Marciniak-Niemcewicz, Anna; Kocik, Janusz

2014-01-01

Abstract The first cluster of hemorrhagic fever with renal syndrome (HFRS) in Poland was identified in 2007 in the Subcarpathian region. The natural environment of this area is a key habitat for hantavirus vectors. The animal reservoir of existing human HFRS clusters was studied to assess the occurrence of viruses (including Tula virus, Puumala virus, and Dobrava–Belgrade virus) among rodents. We examined 70 suspected human cases with symptoms corresponding to the clinical picture of HFRS. Serological analysis (indirect immunofluorescence assay and immunoblot) confirmed the presence of anti-hantavirus antibodies in 18 patients, which were surveyed with regard to developed symptoms and presumed rodent contact. Seroepidemiological analysis of newly confirmed human cases was performed, putative areas of human exposure were studied, and 194 rodents were subsequently captured from identified areas. Internal organs (lungs, heart, spleen, bladder, and kidneys) were collected from 64 Apodemus flavicollis, 55 Apodemus agrarius, 40 Myodes glareolus, 21 Mus musculus, and 14 Microtus arvalis and tested for the presence of hantavirus RNA by reverse transcription and subsequent real-time PCR. Positive samples were also tested by indirect immunofluorescence. Animal reservoir surveillance enabled the first detection of Puumala virus and Dobrava–Belgrade virus among animals in Poland. Furthermore, some places where rodents were captured correlated with areas of residence of laboratory-confirmed human cases and likely detected virus species. Moreover, three species of hantaviruses coexisting in a relatively small area were identified. PMID:24902039

Addressing challenges to human health in the Anthropocene epoch-an overview of the findings of the Rockefeller/Lancet Commission on Planetary Health.

PubMed

Haines, Andy

The report of the Rockefeller Foundation/Lancet Commission on Planetary Health described how human health directly depends upon the environment. It takes a broad perspective not only acknowledging climate change as the most important global environmental threat to health but also recognizing other impacts, including dramatic loss of tropical forests, land degradation, loss of biodiversity, declining freshwater resources, ocean acidification, and over-exploitation of fisheries. All pose challenges to human health gains, leading to the concept of planetary health-that the human condition is tied to natural systems. The Planetary Health Commission report highlights several major concerns arising from environmental change including impacts on food availability and quality, increases in natural disasters and population displacement, and newly emerging diseases, e.g. from zoonotic infections. Three challenges emerge from the report: the first is imagination, or conceptual challenges-better metrics are needed to assess human progress within the context of environmental change; the second is a lack of relevant knowledge, requiring more research on the inter-linkages between environmental change and health and on the effectiveness of potential solutions; and the third is implementation of solutions, ensuring that the science is translated into policy and practice. There are many opportunities to promote planetary health including developing sustainable and healthy cities, encouraging more resilient health systems and disaster preparedness, reducing food waste, preserving ecosystems, and redirecting harmful subsidies in food, agriculture, fishery and energy sectors. Many current trends are driven by inequitable, inefficient, and unsustainable patterns of resource consumption and technological development, coupled with population growth, but solutions lie within reach. Prosperity must be redefined as an enhancement of the quality of life and the delivery of improved health for all, together with respect for natural systems.

Histomorphometric analysis of newly formed bone after bilateral maxillary sinus augmentation using two different osteoconductive materials and internal collagen membrane.

PubMed

Kolerman, Roni; Samorodnitzky-Naveh, Gili R; Barnea, Eitan; Tal, Haim

2012-02-01

Deproteinized bovine bone mineral (DBBM) and human freeze-dried bone allograft (FDBA) were compared in five patients undergoing bilateral maxillary sinus floor augmentation using DBBM on one side and FDBA on the contralateral side. After 9 months, core biopsy specimens were harvested. Mean newly formed bone values were 31.8% and 27.2% at FDBA and DBBM sites, respectively (P = .451); mean residual graft particle values were 21.5% and 24.2%, respectively (P = .619); and mean connective tissue values were 46.7% and 48.6%, respectively (P = .566). Within the limits of the present study, it is suggested that both graft materials are equally suitable for sinus augmentation.

A novel far-red fluorescent xenograft model of ovarian carcinoma for preclinical evaluation of HER2-targeted immunotoxins

PubMed Central

Zdobnova, Tatiana; Sokolova, Evgeniya; Stremovskiy, Oleg; Karpenko, Dmitry; Telford, William; Turchin, Ilya; Balalaeva, Irina; Deyev, Sergey

2015-01-01

We have created a novel fluorescent model of a human ovarian carcinoma xenograft overexpressing receptor HER2, a promising molecular target of solid tumors. The model is based on a newly generated SKOV-kat cell line stably expressing far-red fluorescent protein Katushka. Katushka is most suitable for the in vivo imaging due to an optimal combination of high brightness and emission in the “window of tissue transparency”. The relevance of the fluorescent model for the in vivo monitoring of tumor growth and response to treatment was demonstrated using a newly created HER2-targeted recombinant immunotoxin based on the 4D5scFv antibody and a fragment of the Pseudomonas exotoxin A. PMID:26436696

Identification and preliminary characterization of a protein motif related to the zinc finger.

PubMed Central

Lovering, R; Hanson, I M; Borden, K L; Martin, S; O'Reilly, N J; Evan, G I; Rahman, D; Pappin, D J; Trowsdale, J; Freemont, P S

1993-01-01

We have identified a protein motif, related to the zinc finger, which defines a newly discovered family of proteins. The motif was found in the sequence of the human RING1 gene, which is proximal to the major histocompatibility complex region on chromosome six. We propose naming this motif the "RING finger" and it is found in 27 proteins, all of which have putative DNA binding functions. We have synthesized a peptide corresponding to the RING1 motif and examined a number of properties, including metal and DNA binding. We provide evidence to support the suggestion that the RING finger motif is the DNA binding domain of this newly defined family of proteins. Images Fig. 1 Fig. 4 PMID:7681583

A Developmental Approach to the Teaching of Ethical Decision Making.

ERIC Educational Resources Information Center

Neukrug, Edward S.

1996-01-01

Examines the newly adopted code of ethics, reviews some ethical decision-making models, and hypothesizes how the maturity of a student might mediate the effective use of codes and of decision-making models. Provides a model for human service educators that integrates ethical guidelines and ethical decision-making models. (RJM)

Designing Media and ICT Strategies for Non-Formal Education in Eritrea

ERIC Educational Resources Information Center

Murthy, C. S. H. N.

2006-01-01

Designing media and ICT strategies for a newly formed country like Eritrea, which has endured 30 years of armed struggle, leading to massive destruction followed by serial drought, is fraught with numerous constraints: limitation of human resources (e.g. qualified personnel), infrastructure and financial constraints. At the same time, though it…

Employers' Views on the Value of Older Workers. Final Report.

ERIC Educational Resources Information Center

University of Southern Maine, Portland. Human Services Development Inst.

A study examined the extent to which organizations in three New England states valued newly hired older workers. Telephone interviews were conducted with 105 directors of human resources (DHRs) and with 113 director supervisors from a broad range of organizations. Major dependent variables were general employer motivations and expectations related…

Borrelia miyamotoi–Associated Neuroborreliosis in Immunocompromised Person

PubMed Central

Lobenstein, Sabine; Hermann, Beate; Margos, Gabriele; Fingerle, Volker

2016-01-01

Borrelia miyamotoi is a newly recognized human pathogen in the relapsing fever group of spirochetes. We investigated a case of B. miyamotoi infection of the central nervous system resembling B. burgdorferi–induced Lyme neuroborreliosis and determined that this emergent agent of central nervous system infection can be diagnosed with existing methods. PMID:27533748

Education in the Anthropocene: Ethico-Moral Dimensions and Critical Realist Openings

ERIC Educational Resources Information Center

Olvitt, Lausanne Laura

2017-01-01

Human-induced changes in planetary bio-geo-chemical processes have tipped earth into a newly-proposed geological epoch: the Anthropocene, which places moral and ethical demands on people regarding who should take responsibility for the well-being of people and planet, how, and why. Drawing generally on critical realist ontology, and more…

Immune modulation by Baccillus subtilis-based direct-fed microbials in commercial broiler chickens

USDA-ARS?s Scientific Manuscript database

Direct-fed microbials (DFMs), also known as probiotics have been successfully used to improve the balance of gut microflora. Spores of Bacillus subtilis (B. subtilis), have been used as DFMs for food animals and humans, and our previous studies showed that dietary supplementation of newly hatched br...