NMDA receptor dysfunction in autism spectrum disorders.

PubMed

Lee, Eun-Jae; Choi, Su Yeon; Kim, Eunjoon

2015-02-01

Abnormalities and imbalances in neuronal excitatory and inhibitory synapses have been implicated in diverse neuropsychiatric disorders including autism spectrum disorders (ASDs). Increasing evidence indicates that dysfunction of NMDA receptors (NMDARs) at excitatory synapses is associated with ASDs. In support of this, human ASD-associated genetic variations are found in genes encoding NMDAR subunits. Pharmacological enhancement or suppression of NMDAR function ameliorates ASD symptoms in humans. Animal models of ASD display bidirectional NMDAR dysfunction, and correcting this deficit rescues ASD-like behaviors. These findings suggest that deviation of NMDAR function in either direction contributes to the development of ASDs, and that correcting NMDAR dysfunction has therapeutic potential for ASDs. Copyright © 2014 Elsevier Ltd. All rights reserved.

MR-guided adaptive focusing of therapeutic ultrasound beams in the human head

PubMed Central

Marsac, Laurent; Chauvet, Dorian; Larrat, Benoît; Pernot, Mathieu; Robert, B.; Fink, Mathias; Boch, Anne-Laure; Aubry, Jean-François; Tanter, Mickaël

2012-01-01

Purpose This study aims to demonstrate, using human cadavers the feasibility of energy-based adaptive focusing of ultrasonic waves using Magnetic Resonance Acoustic Radiation Force Imaging (MR-ARFI) in the framework of non-invasive transcranial High Intensity Focused Ultrasound (HIFU) therapy. Methods Energy-based adaptive focusing techniques were recently proposed in order to achieve aberration correction. We evaluate this method on a clinical brain HIFU system composed of 512 ultrasonic elements positioned inside a full body 1.5 T clinical Magnetic Resonance (MR) imaging system. Cadaver heads were mounted onto a clinical Leksell stereotactic frame. The ultrasonic wave intensity at the chosen location was indirectly estimated by the MR system measuring the local tissue displacement induced by the acoustic radiation force of the ultrasound (US) beams. For aberration correction, a set of spatially encoded ultrasonic waves was transmitted from the ultrasonic array and the resulting local displacements were estimated with the MR-ARFI sequence for each emitted beam. A non-iterative inversion process was then performed in order to estimate the spatial phase aberrations induced by the cadaver skull. The procedure was first evaluated and optimized in a calf brain using a numerical aberrator mimicking human skull aberrations. The full method was then demonstrated using a fresh human cadaver head. Results The corrected beam resulting from the direct inversion process was found to focus at the targeted location with an acoustic intensity 2.2 times higher than the conventional non corrected beam. In addition, this corrected beam was found to give an acoustic intensity 1.5 times higher than the focusing pattern obtained with an aberration correction using transcranial acoustic simulation based on X-ray computed tomography (CT) scans. Conclusion The proposed technique achieved near optimal focusing in an intact human head for the first time. These findings confirm the strong potential of energy-based adaptive focusing of transcranial ultrasonic beams for clinical applications. PMID:22320825

Vertex evoked potentials in a rating-scale detection task: Relation to signal probability

NASA Technical Reports Server (NTRS)

Squires, K. C.; Squires, N. K.; Hillyard, S. A.

1974-01-01

Vertex evoked potentials were recorded from human subjects performing in an auditory detection task with rating scale responses. Three values of a priori probability of signal presentation were tested. The amplitudes of the N1 and P3 components of the vertex potential associated with correct detections of the signal were found to be systematically related to the strictness of the response criterion and independent of variations in a priori signal probability. No similar evoked potential components were found associated with signal absent judgements (misses and correct rejections) regardless of the confidence level of the judgement or signal probability. These results strongly support the contention that the form of the vertex evoked response is closely correlated with the subject's psychophysical decision regarding the presence or absence of a threshold level signal.

Comparable change in stromal refractive index of cat and human corneas following blue-IRIS.

PubMed

Wozniak, Kaitlin T; Gearhart, Sara M; Savage, Daniel E; Ellis, Jonathan D; Knox, Wayne H; Huxlin, Krystel R

2017-05-01

Blue intratissue refractive index shaping (blue-IRIS) is a method with potential to correct ocular refraction noninvasively in humans. To date, blue-IRIS has only ever been applied to cat corneas and hydrogels. To test the comparability of refractive index change achievable in cat and human tissues, we used blue-IRIS to write identical phase gratings in ex vivo feline and human corneas. Femtosecond pulses (400 nm) were focused ? 300 ?? ? m below the epithelial surface of excised cat and human corneas and scanned to write phase gratings with lines ? 1 ?? ? m wide, spaced 5 ?? ? m apart, using a scan speed of 5 ?? mm / s . Additional cat corneas were used to test writing at 3 and 7 ?? mm / s in order to document speed dependence of the refractive index change magnitude. The first-order diffraction efficiency was immediately measured and used to calculate the refractive index change attained. Our data show that blue-IRIS induces comparable refractive index changes in feline and human corneas, an essential requirement for further developing its use as a clinical vision correction technique.

Comparable change in stromal refractive index of cat and human corneas following blue-IRIS

NASA Astrophysics Data System (ADS)

Wozniak, Kaitlin T.; Gearhart, Sara M.; Savage, Daniel E.; Ellis, Jonathan D.; Knox, Wayne H.; Huxlin, Krystel R.

2017-05-01

Blue intratissue refractive index shaping (blue-IRIS) is a method with potential to correct ocular refraction noninvasively in humans. To date, blue-IRIS has only ever been applied to cat corneas and hydrogels. To test the comparability of refractive index change achievable in cat and human tissues, we used blue-IRIS to write identical phase gratings in ex vivo feline and human corneas. Femtosecond pulses (400 nm) were focused ˜300 μm below the epithelial surface of excised cat and human corneas and scanned to write phase gratings with lines ˜1 μm wide, spaced 5 μm apart, using a scan speed of 5 mm/s. Additional cat corneas were used to test writing at 3 and 7 mm/s in order to document speed dependence of the refractive index change magnitude. The first-order diffraction efficiency was immediately measured and used to calculate the refractive index change attained. Our data show that blue-IRIS induces comparable refractive index changes in feline and human corneas, an essential requirement for further developing its use as a clinical vision correction technique.

Genetic correction of β-thalassemia patient-specific iPS cells and its use in improving hemoglobin production in irradiated SCID mice.

PubMed

Wang, Yixuan; Zheng, Chen-Guang; Jiang, Yonghua; Zhang, Jiqin; Chen, Jiayu; Yao, Chao; Zhao, Qingguo; Liu, Sheng; Chen, Ke; Du, Juan; Yang, Ze; Gao, Shaorong

2012-04-01

The generation of induced pluripotent stem cells (iPSCs) from differentiated somatic cells by over-expression of several transcription factors has the potential to cure many genetic and degenerative diseases currently recalcitrant to traditional clinical approaches. One such genetic disease is β-thalassemia major (Cooley's anemia). This disease is caused by either a point mutation or the deletion of several nucleotides in the β-globin gene, and it threatens the lives of millions of people in China. In the present study, we successfully generated iPSCs from fibroblasts collected from a 2-year-old patient who was diagnosed with a homozygous 41/42 deletion in his β-globin gene. More importantly, we successfully corrected this genetic mutation in the β-thalassemia iPSCs by homologous recombination. Furthermore, transplantation of the genetically corrected iPSCs-derived hematopoietic progenitors into sub-lethally irradiated immune deficient SCID mice showed improved hemoglobin production compared with the uncorrected iPSCs. Moreover, the generation of human β-globin could be detected in the mice transplanted with corrected iPSCs-derived hematopietic progenitors. Our study provides strong evidence that iPSCs generated from a patient with a genetic disease can be corrected by homologous recombination and that the corrected iPSCs have potential clinical uses.

Evolving regulatory paradigm for proarrhythmic risk assessment for new drugs.

PubMed

Vicente, Jose; Stockbridge, Norman; Strauss, David G

Fourteen drugs were removed from the market worldwide because their potential to cause torsade de pointes (torsade), a potentially fatal ventricular arrhythmia. The observation that most drugs that cause torsade block the potassium channel encoded by the human ether-à-go-go related gene (hERG) and prolong the heart rate corrected QT interval (QTc) on the ECG, led to a focus on screening new drugs for their potential to block the hERG potassium channel and prolong QTc. This has been a successful strategy keeping torsadogenic drugs off the market, but has resulted in drugs being dropped from development, sometimes inappropriately. This is because not all drugs that block the hERG potassium channel and prolong QTc cause torsade, sometimes because they block other channels. The regulatory paradigm is evolving to improve proarrhythmic risk prediction. ECG studies can now use exposure-response modeling for assessing the effect of a drug on the QTc in small sample size first-in-human studies. Furthermore, the Comprehensive in vitro Proarrhythmia Assay (CiPA) initiative is developing and validating a new in vitro paradigm for cardiac safety evaluation of new drugs that provides a more accurate and comprehensive mechanistic-based assessment of proarrhythmic potential. Under CiPA, the prediction of proarrhythmic potential will come from in vitro ion channel assessments coupled with an in silico model of the human ventricular myocyte. The preclinical assessment will be checked with an assessment of human phase 1 ECG data to determine if there are unexpected ion channel effects in humans compared to preclinical ion channel data. While there is ongoing validation work, the heart rate corrected J-T peak interval is likely to be assessed under CiPA to detect inward current block in presence of hERG potassium channel block. Copyright © 2016 Elsevier Inc. All rights reserved.

Repair of Thalassemic Human β -globin mRNA in Mammalian Cells by Antisense Oligonucleotides

NASA Astrophysics Data System (ADS)

Sierakowska, Halina; Sambade, Maria J.; Agrawal, Sudhir; Kole, Ryszard

1996-11-01

In one form of β -thalassemia, a genetic blood disorder, a mutation in intron 2 of the β -globin gene (IVS2-654) causes aberrant splicing of β -globin pre-mRNA and, consequently, β -globin deficiency. Treatment of mammalian cells stably expressing the IVS2-654 human β -globin gene with antisense oligonucleotides targeted at the aberrant splice sites restored correct splicing in a dose-dependent fashion, generating correct human β -globin mRNA and polypeptide. Both products persisted for up to 72 hr posttreatment. The oligonucleotides modified splicing by a true antisense mechanism without overt unspecific effects on cell growth and splicing of other pre-mRNAs. This novel approach in which antisense oligonucleotides are used to restore rather than to down-regulate the activity of the target gene is applicable to other splicing mutants and is of potential clinical interest.

Alpharetroviral Vector-mediated Gene Therapy for X-CGD: Functional Correction and Lack of Aberrant Splicing

PubMed Central

Kaufmann, Kerstin B.; Brendel, Christian; Suerth, Julia D.; Mueller-Kuller, Uta; Chen-Wichmann, Linping; Schwäble, Joachim; Pahujani, Shweta; Kunkel, Hana; Schambach, Axel; Baum, Christopher; Grez, Manuel

2013-01-01

Comparative integrome analysis has revealed that the most neutral integration pattern among retroviruses is attributed to alpharetroviruses. We chose X-linked chronic granulomatous disease (X-CGD) as model to evaluate the potential of self-inactivating (SIN) alpharetroviral vectors for gene therapy of monogenic diseases. Therefore, we combined the alpharetroviral vector backbone with the elongation factor-1α short promoter, both considered to possess a low genotoxic profile, to drive transgene (gp91phox) expression. Following efficient transduction transgene expression was sustained and provided functional correction of the CGD phenotype in a cell line model at low vector copy number. Further analysis in a murine X-CGD transplantation model revealed gene-marking of bone marrow cells and oxidase positive granulocytes in peripheral blood. Transduction of human X-CGD CD34+ cells provided functional correction up to wild-type levels and long-term expression upon transplantation into a humanized mouse model. In contrast to lentiviral vectors, no aberrantly spliced transcripts containing cellular exons fused to alpharetroviral sequences were found in transduced cells, implying that the safety profile of alpharetroviral vectors may extend beyond their neutral integration profile. Taken together, this highlights the potential of this SIN alpharetroviral system as a platform for new candidate vectors for future gene therapy of hematopoietic disorders. PMID:23207695

Radiocarbon dating uncertainty and the reliability of the PEWMA method of time-series analysis for research on long-term human-environment interaction

PubMed Central

Carleton, W. Christopher; Campbell, David

2018-01-01

Statistical time-series analysis has the potential to improve our understanding of human-environment interaction in deep time. However, radiocarbon dating—the most common chronometric technique in archaeological and palaeoenvironmental research—creates challenges for established statistical methods. The methods assume that observations in a time-series are precisely dated, but this assumption is often violated when calibrated radiocarbon dates are used because they usually have highly irregular uncertainties. As a result, it is unclear whether the methods can be reliably used on radiocarbon-dated time-series. With this in mind, we conducted a large simulation study to investigate the impact of chronological uncertainty on a potentially useful time-series method. The method is a type of regression involving a prediction algorithm called the Poisson Exponentially Weighted Moving Average (PEMWA). It is designed for use with count time-series data, which makes it applicable to a wide range of questions about human-environment interaction in deep time. Our simulations suggest that the PEWMA method can often correctly identify relationships between time-series despite chronological uncertainty. When two time-series are correlated with a coefficient of 0.25, the method is able to identify that relationship correctly 20–30% of the time, providing the time-series contain low noise levels. With correlations of around 0.5, it is capable of correctly identifying correlations despite chronological uncertainty more than 90% of the time. While further testing is desirable, these findings indicate that the method can be used to test hypotheses about long-term human-environment interaction with a reasonable degree of confidence. PMID:29351329

Radiocarbon dating uncertainty and the reliability of the PEWMA method of time-series analysis for research on long-term human-environment interaction.

PubMed

Carleton, W Christopher; Campbell, David; Collard, Mark

2018-01-01

Statistical time-series analysis has the potential to improve our understanding of human-environment interaction in deep time. However, radiocarbon dating-the most common chronometric technique in archaeological and palaeoenvironmental research-creates challenges for established statistical methods. The methods assume that observations in a time-series are precisely dated, but this assumption is often violated when calibrated radiocarbon dates are used because they usually have highly irregular uncertainties. As a result, it is unclear whether the methods can be reliably used on radiocarbon-dated time-series. With this in mind, we conducted a large simulation study to investigate the impact of chronological uncertainty on a potentially useful time-series method. The method is a type of regression involving a prediction algorithm called the Poisson Exponentially Weighted Moving Average (PEMWA). It is designed for use with count time-series data, which makes it applicable to a wide range of questions about human-environment interaction in deep time. Our simulations suggest that the PEWMA method can often correctly identify relationships between time-series despite chronological uncertainty. When two time-series are correlated with a coefficient of 0.25, the method is able to identify that relationship correctly 20-30% of the time, providing the time-series contain low noise levels. With correlations of around 0.5, it is capable of correctly identifying correlations despite chronological uncertainty more than 90% of the time. While further testing is desirable, these findings indicate that the method can be used to test hypotheses about long-term human-environment interaction with a reasonable degree of confidence.

The Names Have Been Changed to Protect the . . . Humanity: Person-First Language in Correctional Health Epidemiology.

PubMed

Bedell, Precious S; Spaulding, Anne C; So, Marvin; Sarrett, Jennifer C

2018-06-01

After objections surfaced following a call for papers on "Prisoner Health," the editors of Epidemiologic Reviews decided to rename this year's volume "Incarceration and Health." In this commentary, we trace the origins of person-first language and explain why using appropriate terms in correctional health, including correctional health epidemiology, matters. We discuss the potential consequences of person-first language for justice-involved individuals and how inclusive language might affect the social, emotional, and physical well-being of individuals, families, and communities. Future directions may include measuring health outcomes when language is systematically changed. The barriers that thwart successful reentry may wane when dehumanizing language disappears.

The Combination of CRISPR/Cas9 and iPSC Technologies in the Gene Therapy of Human β-thalassemia in Mice.

PubMed

Ou, Zhanhui; Niu, Xiaohua; He, Wenyin; Chen, Yuchang; Song, Bing; Xian, Yexing; Fan, Di; Tang, Daolin; Sun, Xiaofang

2016-09-01

β-thalassemia results from point mutations or small deletions in the β-globin (HBB) gene that ultimately cause anemia. The generation of induced pluripotent stem cells (iPSCs) from the somatic cells of patients in combination with subsequent homologous recombination-based gene correction provides new approaches to cure this disease. CRISPR/Cas9 is a genome editing tool that is creating a buzz in the scientific community for treating human diseases, especially genetic disorders. Here, we reported that correction of β-thalassemia mutations in patient-specific iPSCs using the CRISPR/Cas9 tool promotes hematopoietic differentiation in vivo. CRISPR/Cas9-corrected iPSC-derived hematopoietic stem cells (HSCs) were injected into sublethally-irradiated NOD-scid-IL2Rg-/- (NSI) mice. HBB expression was observed in these HSCs after hematopoietic differentiation in the NSI mice. Importantly, no tumor was found in the livers, lungs, kidneys, or bone marrow at 10 weeks in the NSI mice after implantation with these HSCs. Collectively, our findings demonstrated that CRISPR/Cas9 successfully corrects β-thalassemia mutations in patient-specific iPSCs. These CRISPR/Cas9-corrected iPSC-derived HSCs express normal HBB in mice without tumorigenic potential, suggesting a safe strategy for personalized treatment of β-thalassemia.

CRISPR/Cas9-mediated correction of human genetic disease.

PubMed

Men, Ke; Duan, Xingmei; He, Zhiyao; Yang, Yang; Yao, Shaohua; Wei, Yuquan

2017-05-01

The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) protein 9 system (CRISPR/Cas9) provides a powerful tool for targeted genetic editing. Directed by programmable sequence-specific RNAs, this system introduces cleavage and double-stranded breaks at target sites precisely. Compared to previously developed targeted nucleases, the CRISPR/Cas9 system demonstrates several promising advantages, including simplicity, high specificity, and efficiency. Several broad genome-editing studies with the CRISPR/Cas9 system in different species in vivo and ex vivo have indicated its strong potential, raising hopes for therapeutic genome editing in clinical settings. Taking advantage of non-homologous end-joining (NHEJ) and homology directed repair (HDR)-mediated DNA repair, several studies have recently reported the use of CRISPR/Cas9 to successfully correct disease-causing alleles ranging from single base mutations to large insertions. In this review, we summarize and discuss recent preclinical studies involving the CRISPR/Cas9-mediated correction of human genetic diseases.

A Critical Meta-Analysis of Lens Model Studies in Human Judgment and Decision-Making

PubMed Central

Kaufmann, Esther; Reips, Ulf-Dietrich; Wittmann, Werner W.

2013-01-01

Achieving accurate judgment (‘judgmental achievement’) is of utmost importance in daily life across multiple domains. The lens model and the lens model equation provide useful frameworks for modeling components of judgmental achievement and for creating tools to help decision makers (e.g., physicians, teachers) reach better judgments (e.g., a correct diagnosis, an accurate estimation of intelligence). Previous meta-analyses of judgment and decision-making studies have attempted to evaluate overall judgmental achievement and have provided the basis for evaluating the success of bootstrapping (i.e., replacing judges by linear models that guide decision making). However, previous meta-analyses have failed to appropriately correct for a number of study design artifacts (e.g., measurement error, dichotomization), which may have potentially biased estimations (e.g., of the variability between studies) and led to erroneous interpretations (e.g., with regards to moderator variables). In the current study we therefore conduct the first psychometric meta-analysis of judgmental achievement studies that corrects for a number of study design artifacts. We identified 31 lens model studies (N = 1,151, k = 49) that met our inclusion criteria. We evaluated overall judgmental achievement as well as whether judgmental achievement depended on decision domain (e.g., medicine, education) and/or the level of expertise (expert vs. novice). We also evaluated whether using corrected estimates affected conclusions with regards to the success of bootstrapping with psychometrically-corrected models. Further, we introduce a new psychometric trim-and-fill method to estimate the effect sizes of potentially missing studies correct psychometric meta-analyses for effects of publication bias. Comparison of the results of the psychometric meta-analysis with the results of a traditional meta-analysis (which only corrected for sampling error) indicated that artifact correction leads to a) an increase in values of the lens model components, b) reduced heterogeneity between studies, and c) increases the success of bootstrapping. We argue that psychometric meta-analysis is useful for accurately evaluating human judgment and show the success of bootstrapping. PMID:24391781

A critical meta-analysis of lens model studies in human judgment and decision-making.

PubMed

Kaufmann, Esther; Reips, Ulf-Dietrich; Wittmann, Werner W

2013-01-01

Achieving accurate judgment ('judgmental achievement') is of utmost importance in daily life across multiple domains. The lens model and the lens model equation provide useful frameworks for modeling components of judgmental achievement and for creating tools to help decision makers (e.g., physicians, teachers) reach better judgments (e.g., a correct diagnosis, an accurate estimation of intelligence). Previous meta-analyses of judgment and decision-making studies have attempted to evaluate overall judgmental achievement and have provided the basis for evaluating the success of bootstrapping (i.e., replacing judges by linear models that guide decision making). However, previous meta-analyses have failed to appropriately correct for a number of study design artifacts (e.g., measurement error, dichotomization), which may have potentially biased estimations (e.g., of the variability between studies) and led to erroneous interpretations (e.g., with regards to moderator variables). In the current study we therefore conduct the first psychometric meta-analysis of judgmental achievement studies that corrects for a number of study design artifacts. We identified 31 lens model studies (N = 1,151, k = 49) that met our inclusion criteria. We evaluated overall judgmental achievement as well as whether judgmental achievement depended on decision domain (e.g., medicine, education) and/or the level of expertise (expert vs. novice). We also evaluated whether using corrected estimates affected conclusions with regards to the success of bootstrapping with psychometrically-corrected models. Further, we introduce a new psychometric trim-and-fill method to estimate the effect sizes of potentially missing studies correct psychometric meta-analyses for effects of publication bias. Comparison of the results of the psychometric meta-analysis with the results of a traditional meta-analysis (which only corrected for sampling error) indicated that artifact correction leads to a) an increase in values of the lens model components, b) reduced heterogeneity between studies, and c) increases the success of bootstrapping. We argue that psychometric meta-analysis is useful for accurately evaluating human judgment and show the success of bootstrapping.

CRISPR Correction of a Homozygous Low-Density Lipoprotein Receptor Mutation in Familial Hypercholesterolemia Induced Pluripotent Stem Cells.

PubMed

Omer, Linda; Hudson, Elizabeth A; Zheng, Shirong; Hoying, James B; Shan, Yuan; Boyd, Nolan L

2017-11-01

Familial hypercholesterolemia (FH) is a hereditary disease primarily due to mutations in the low-density lipoprotein receptor (LDLR) that lead to elevated cholesterol and premature development of cardiovascular disease. Homozygous FH patients (HoFH) with two dysfunctional LDLR alleles are not as successfully treated with standard hypercholesterol therapies, and more aggressive therapeutic approaches to control cholesterol levels must be considered. Liver transplant can resolve HoFH, and hepatocyte transplantation has shown promising results in animals and humans. However, demand for donated livers and high-quality hepatocytes overwhelm the supply. Human pluripotent stem cells can differentiate to hepatocyte-like cells (HLCs) with the potential for experimental and clinical use. To be of future clinical use as autologous cells, LDLR genetic mutations in derived FH-HLCs need to be corrected. Genome editing technology clustered-regularly-interspaced-short-palindromic-repeats/CRISPR-associated 9 (CRISPR/Cas9) can repair pathologic genetic mutations in human induced pluripotent stem cells. We used CRISPR/Cas9 genome editing to permanently correct a 3-base pair homozygous deletion in LDLR exon 4 of patient-derived HoFH induced pluripotent stem cells. The genetic correction restored LDLR-mediated endocytosis in FH-HLCs and demonstrates the proof-of-principle that CRISPR-mediated genetic modification can be successfully used to normalize HoFH cholesterol metabolism deficiency at the cellular level.

Reversible immortalisation enables genetic correction of human muscle progenitors and engineering of next-generation human artificial chromosomes for Duchenne muscular dystrophy.

PubMed

Benedetti, Sara; Uno, Narumi; Hoshiya, Hidetoshi; Ragazzi, Martina; Ferrari, Giulia; Kazuki, Yasuhiro; Moyle, Louise Anne; Tonlorenzi, Rossana; Lombardo, Angelo; Chaouch, Soraya; Mouly, Vincent; Moore, Marc; Popplewell, Linda; Kazuki, Kanako; Katoh, Motonobu; Naldini, Luigi; Dickson, George; Messina, Graziella; Oshimura, Mitsuo; Cossu, Giulio; Tedesco, Francesco Saverio

2018-02-01

Transferring large or multiple genes into primary human stem/progenitor cells is challenged by restrictions in vector capacity, and this hurdle limits the success of gene therapy. A paradigm is Duchenne muscular dystrophy (DMD), an incurable disorder caused by mutations in the largest human gene: dystrophin. The combination of large-capacity vectors, such as human artificial chromosomes (HACs), with stem/progenitor cells may overcome this limitation. We previously reported amelioration of the dystrophic phenotype in mice transplanted with murine muscle progenitors containing a HAC with the entire dystrophin locus (DYS-HAC). However, translation of this strategy to human muscle progenitors requires extension of their proliferative potential to withstand clonal cell expansion after HAC transfer. Here, we show that reversible cell immortalisation mediated by lentivirally delivered excisable hTERT and Bmi1 transgenes extended cell proliferation, enabling transfer of a novel DYS-HAC into DMD satellite cell-derived myoblasts and perivascular cell-derived mesoangioblasts. Genetically corrected cells maintained a stable karyotype, did not undergo tumorigenic transformation and retained their migration ability. Cells remained myogenic in vitro (spontaneously or upon MyoD induction) and engrafted murine skeletal muscle upon transplantation. Finally, we combined the aforementioned functions into a next-generation HAC capable of delivering reversible immortalisation, complete genetic correction, additional dystrophin expression, inducible differentiation and controllable cell death. This work establishes a novel platform for complex gene transfer into clinically relevant human muscle progenitors for DMD gene therapy. © 2017 The Authors. Published under the terms of the CC BY 4.0 license.

Functional requirements for the man-vehicle systems research facility. [identifying and correcting human errors during flight simulation

NASA Technical Reports Server (NTRS)

Clement, W. F.; Allen, R. W.; Heffley, R. K.; Jewell, W. F.; Jex, H. R.; Mcruer, D. T.; Schulman, T. M.; Stapleford, R. L.

1980-01-01

The NASA Ames Research Center proposed a man-vehicle systems research facility to support flight simulation studies which are needed for identifying and correcting the sources of human error associated with current and future air carrier operations. The organization of research facility is reviewed and functional requirements and related priorities for the facility are recommended based on a review of potentially critical operational scenarios. Requirements are included for the experimenter's simulation control and data acquisition functions, as well as for the visual field, motion, sound, computation, crew station, and intercommunications subsystems. The related issues of functional fidelity and level of simulation are addressed, and specific criteria for quantitative assessment of various aspects of fidelity are offered. Recommendations for facility integration, checkout, and staffing are included.

Corrective Action Investigation Plan for Corrective Action Unit 527: Horn Silver Mine, Nevada Test Site, Nevada: Revision 1 (Including Records of Technical Change No.1, 2, 3, and 4)

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

U.S. Department of Energy, National Nuclear Security Administration Nevada Operations Office

This Corrective Action Investigation Plan contains the U.S. Department of Energy (DOE), National Nuclear Security Administration Nevada Operations Office's approach to collect the data necessary to evaluate corrective action alternatives appropriate for the closure of Corrective Action Unit (CAU) 527, Horn Silver Mine, Nevada Test Site, Nevada, under the Federal Facility Agreement and Consent Order. Corrective Action Unit 527 consists of one Corrective Action Site (CAS): 26-20-01, Contaminated Waste Dump No.1. The site is located in an abandoned mine site in Area 26 (which is the most arid part of the NTS) approximately 65 miles northwest of Las Vegas. Historicalmore » documents may refer to this site as CAU 168, CWD-1, the Wingfield mine (or shaft), and the Wahmonie mine (or shaft). Historical documentation indicates that between 1959 and the 1970s, nonliquid classified material and unclassified waste was placed in the Horn Silver Mine's shaft. Some of the waste is known to be radioactive. Documentation indicates that the waste is present from 150 feet to the bottom of the mine (500 ft below ground surface). This CAU is being investigated because hazardous constituents migrating from materials and/or wastes disposed of in the Horn Silver Mine may pose a threat to human health and the environment as well as to assess the potential impacts associated with any potential releases from the waste. The results of this field investigation will support a defensible evaluation of corrective action alternatives in the corrective action decision document.« less

Automatic Speech Recognition in Air Traffic Control: a Human Factors Perspective

NASA Technical Reports Server (NTRS)

Karlsson, Joakim

1990-01-01

The introduction of Automatic Speech Recognition (ASR) technology into the Air Traffic Control (ATC) system has the potential to improve overall safety and efficiency. However, because ASR technology is inherently a part of the man-machine interface between the user and the system, the human factors issues involved must be addressed. Here, some of the human factors problems are identified and related methods of investigation are presented. Research at M.I.T.'s Flight Transportation Laboratory is being conducted from a human factors perspective, focusing on intelligent parser design, presentation of feedback, error correction strategy design, and optimal choice of input modalities.

CORRECTIVE ACTION DECISION DOCUMENT FOR AREA 9 UXO LANDFILL, TONOPAH TEST RNGE, CAU 453, REVISION 0, MARCH 1998

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

none

1998-03-01

This Corrective Action Decision Document (CADD) has been prepared for the Area 9 Unexploded Ordnance (UXO) Landfill (Corrective Action Unit [CAU] 453) in accordance with the Federal Facility Agreement and Consent Order (FFACO) of 1996. Corrective Action Unit 453 is located at the Tonopah Test Range (TTR), Nevada, and is comprised of three individual landfill cells located northwest of Area 9. The cells are listed as one Corrective Action Site (CAS) 09-55-001-0952. The landfill cells have been designated as: � Cell A9-1 � Cell A9-2 � Cell A9-3 The purpose of this CADD is to identify and provide a rationalemore » for the selection of a recommended corrective action alternative for CAU 453. The scope of this CADD consists of the following tasks: � Develop corrective action objectives. � Identify corrective action alternative screening criteria. � Develop corrective action alternatives. � Perform detailed and comparative evaluations of the corrective action alternatives in relation to the corrective action objectives and screening criteria. � Recommend and justify a preferred corrective action alternative for the CAU. In June and July 1997, a corrective action investigation was performed that consisted of activities set forth in the Corrective Action Investigation Plan (CAIP) (DOE/NV, 1997). Subsurface investigation of the soils surrounding the cells revealed no contaminants of concern (COCs) above preliminary action levels. The cell contents were not investigated due to the potential for live UXO. Details concerning the analytical and investigation results can be found in Appendix A of this CADD. Based on the potential exposure pathways, the following corrective action objectives have been identified for CAU 453: � Prevent or mitigate human exposure to subsurface soils containing COCs, solid waste, and/or UXO. � Prevent adverse impacts to groundwater quality. Based on the review of existing data, future land use, and current operations at the TTR, the following alternatives have been developed for consideration at the Area 9 UXO Landfill CAU: � Alternative 1 - No Further Action � Alternative 2 - Closure in Place by Administrative Controls � Alternative 3 - Closure in Place by Capping � Alternative 4 - Clean Closure by Removal The corrective action alternatives were evaluated based on four general corrective action standards and five remedy selection decision factors. Based on the results of this evaluation, Alternative 2, Closure in Place by Administrative Controls, was selected as the preferred corrective action alternative. The preferred corrective action alternative was evaluated on its technical merits, focusing on performance, reliability, feasibility, and safety. The alternative was judged to meet all requirements for the technical components evaluated and to represent the most cost-effective corrective action. The alternative meets all applicable state and federal regulations for closure of the site and will reduce potential future exposure pathways to the contents of the landfill. During corrective action implementation, this alternative will present minimal potential threat to site workers. However, appropriate health and safety procedures will be developed and implemented.« less

Analysis of Potential Deep-Seated Landslide in Hekeng Watershed by Environment Indices

NASA Astrophysics Data System (ADS)

Hsieh, C. J.; Chompuchan, C.

2014-12-01

Landslides are a major natural disaster in Taiwan relevant to the human life. After the catastrophic Xiaolin landslide during Typhoon Morakot in August 2009 caused around 400 casualties, the deep-seated landslide has become a serious issue. This study explored the potential deep-seated landslide in Hekeng watershed extracted from SPOT-5 imageries. The empirical topographic correction was applied to minimize effect of the mountain shaded area due to the difference of sun elevation and terrain angle. Consequently the multi-temporal environmental indices, i.e., modified Normalized Difference Vegetation Index (mNDVI) and modified Normalized Difference Water Index (mNDWI) were corrected. Seasonal vegetation cover and surface moisture change were analyzed incorporate with a slope which obtain from DEM data. The result showed that the distribution of potential deep-seated landslide vulnerable area mainly located at headstream watershed. It could be explained that the headstream watershed has less human interference, therefore the environmental indices interpreted those area as deep soil layer and dense vegetation coverage. However, the upstream canal could suffer from the long-term erosion and possibly cause slope toe collapse. In addition, the western watershed is the afforestation zone whereas the eastern watershed is natural forest zone with higher development ratio. The upslope forest management of eastern and western watershed should be discussed variously.

Impact of correction factors in human brain lesion-behavior inference.

PubMed

Sperber, Christoph; Karnath, Hans-Otto

2017-03-01

Statistical voxel-based lesion-behavior mapping (VLBM) in neurological patients with brain lesions is frequently used to examine the relationship between structure and function of the healthy human brain. Only recently, two simulation studies noted reduced anatomical validity of this method, observing the results of VLBM to be systematically misplaced by about 16 mm. However, both simulation studies differed from VLBM analyses of real data in that they lacked the proper use of two correction factors: lesion size and "sufficient lesion affection." In simulation experiments on a sample of 274 real stroke patients, we found that the use of these two correction factors reduced misplacement markedly compared to uncorrected VLBM. Apparently, the misplacement is due to physiological effects of brain lesion anatomy. Voxel-wise topographies of collateral damage in the real data were generated and used to compute a metric for the inter-voxel relation of brain damage. "Anatomical bias" vectors that were solely calculated from these inter-voxel relations in the patients' real anatomical data, successfully predicted the VLBM misplacement. The latter has the potential to help in the development of new VLBM methods that provide even higher anatomical validity than currently available by the proper use of correction factors. Hum Brain Mapp 38:1692-1701, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Validation of Correction Algorithms for Near-IR Analysis of Human Milk in an Independent Sample Set-Effect of Pasteurization.

PubMed

Kotrri, Gynter; Fusch, Gerhard; Kwan, Celia; Choi, Dasol; Choi, Arum; Al Kafi, Nisreen; Rochow, Niels; Fusch, Christoph

2016-02-26

Commercial infrared (IR) milk analyzers are being increasingly used in research settings for the macronutrient measurement of breast milk (BM) prior to its target fortification. These devices, however, may not provide reliable measurement if not properly calibrated. In the current study, we tested a correction algorithm for a Near-IR milk analyzer (Unity SpectraStar, Brookfield, CT, USA) for fat and protein measurements, and examined the effect of pasteurization on the IR matrix and the stability of fat, protein, and lactose. Measurement values generated through Near-IR analysis were compared against those obtained through chemical reference methods to test the correction algorithm for the Near-IR milk analyzer. Macronutrient levels were compared between unpasteurized and pasteurized milk samples to determine the effect of pasteurization on macronutrient stability. The correction algorithm generated for our device was found to be valid for unpasteurized and pasteurized BM. Pasteurization had no effect on the macronutrient levels and the IR matrix of BM. These results show that fat and protein content can be accurately measured and monitored for unpasteurized and pasteurized BM. Of additional importance is the implication that donated human milk, generally low in protein content, has the potential to be target fortified.

Validation of Correction Algorithms for Near-IR Analysis of Human Milk in an Independent Sample Set—Effect of Pasteurization

PubMed Central

Kotrri, Gynter; Fusch, Gerhard; Kwan, Celia; Choi, Dasol; Choi, Arum; Al Kafi, Nisreen; Rochow, Niels; Fusch, Christoph

2016-01-01

Commercial infrared (IR) milk analyzers are being increasingly used in research settings for the macronutrient measurement of breast milk (BM) prior to its target fortification. These devices, however, may not provide reliable measurement if not properly calibrated. In the current study, we tested a correction algorithm for a Near-IR milk analyzer (Unity SpectraStar, Brookfield, CT, USA) for fat and protein measurements, and examined the effect of pasteurization on the IR matrix and the stability of fat, protein, and lactose. Measurement values generated through Near-IR analysis were compared against those obtained through chemical reference methods to test the correction algorithm for the Near-IR milk analyzer. Macronutrient levels were compared between unpasteurized and pasteurized milk samples to determine the effect of pasteurization on macronutrient stability. The correction algorithm generated for our device was found to be valid for unpasteurized and pasteurized BM. Pasteurization had no effect on the macronutrient levels and the IR matrix of BM. These results show that fat and protein content can be accurately measured and monitored for unpasteurized and pasteurized BM. Of additional importance is the implication that donated human milk, generally low in protein content, has the potential to be target fortified. PMID:26927169

Adaptive Optics Analysis of Visual Benefit with Higher-order Aberrations Correction of Human Eye - Poster Paper

NASA Astrophysics Data System (ADS)

Xue, Lixia; Dai, Yun; Rao, Xuejun; Wang, Cheng; Hu, Yiyun; Liu, Qian; Jiang, Wenhan

2008-01-01

Higher-order aberrations correction can improve visual performance of human eye to some extent. To evaluate how much visual benefit can be obtained with higher-order aberrations correction we developed an adaptive optics vision simulator (AOVS). Dynamic real time optimized modal compensation was used to implement various customized higher-order ocular aberrations correction strategies. The experimental results indicate that higher-order aberrations correction can improve visual performance of human eye comparing with only lower-order aberration correction but the improvement degree and higher-order aberration correction strategy are different from each individual. Some subjects can acquire great visual benefit when higher-order aberrations were corrected but some subjects acquire little visual benefit even though all higher-order aberrations were corrected. Therefore, relative to general lower-order aberrations correction strategy, customized higher-order aberrations correction strategy is needed to obtain optimal visual improvement for each individual. AOVS provides an effective tool for higher-order ocular aberrations optometry for customized ocular aberrations correction.

Contact Lenses for Color Blindness.

PubMed

Badawy, Abdel-Rahman; Hassan, Muhammad Umair; Elsherif, Mohamed; Ahmed, Zubair; Yetisen, Ali K; Butt, Haider

2018-06-01

Color vision deficiency (color blindness) is an inherited genetic ocular disorder. While no cure for this disorder currently exists, several methods can be used to increase the color perception of those affected. One such method is the use of color filtering glasses which are based on Bragg filters. While these glasses are effective, they are high cost, bulky, and incompatible with other vision correction eyeglasses. In this work, a rhodamine derivative is incorporated in commercial contact lenses to filter out the specific wavelength bands (≈545-575 nm) to correct color vision blindness. The biocompatibility assessment of the dyed contact lenses in human corneal fibroblasts and human corneal epithelial cells shows no toxicity and cell viability remains at 99% after 72 h. This study demonstrates the potential of the dyed contact lenses in wavelength filtering and color vision deficiency management. © 2018 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Two types of aggression in human evolution.

PubMed

Wrangham, Richard W

2018-01-09

Two major types of aggression, proactive and reactive, are associated with contrasting expression, eliciting factors, neural pathways, development, and function. The distinction is useful for understanding the nature and evolution of human aggression. Compared with many primates, humans have a high propensity for proactive aggression, a trait shared with chimpanzees but not bonobos. By contrast, humans have a low propensity for reactive aggression compared with chimpanzees, and in this respect humans are more bonobo-like. The bimodal classification of human aggression helps solve two important puzzles. First, a long-standing debate about the significance of aggression in human nature is misconceived, because both positions are partly correct. The Hobbes-Huxley position rightly recognizes the high potential for proactive violence, while the Rousseau-Kropotkin position correctly notes the low frequency of reactive aggression. Second, the occurrence of two major types of human aggression solves the execution paradox, concerned with the hypothesized effects of capital punishment on self-domestication in the Pleistocene. The puzzle is that the propensity for aggressive behavior was supposedly reduced as a result of being selected against by capital punishment, but capital punishment is itself an aggressive behavior. Since the aggression used by executioners is proactive, the execution paradox is solved to the extent that the aggressive behavior of which victims were accused was frequently reactive, as has been reported. Both types of killing are important in humans, although proactive killing appears to be typically more frequent in war. The biology of proactive aggression is less well known and merits increased attention.

Stable Gene Targeting in Human Cells Using Single-Strand Oligonucleotides with Modified Bases

PubMed Central

Rios, Xavier; Briggs, Adrian W.; Christodoulou, Danos; Gorham, Josh M.; Seidman, Jonathan G.; Church, George M.

2012-01-01

Recent advances allow multiplexed genome engineering in E. coli, employing easily designed oligonucleotides to edit multiple loci simultaneously. A similar technology in human cells would greatly expedite functional genomics, both by enhancing our ability to test how individual variants such as single nucleotide polymorphisms (SNPs) are related to specific phenotypes, and potentially allowing simultaneous mutation of multiple loci. However, oligo-mediated targeting of human cells is currently limited by low targeting efficiencies and low survival of modified cells. Using a HeLa-based EGFP-rescue reporter system we show that use of modified base analogs can increase targeting efficiency, in part by avoiding the mismatch repair machinery. We investigate the effects of oligonucleotide toxicity and find a strong correlation between the number of phosphorothioate bonds and toxicity. Stably EGFP-corrected cells were generated at a frequency of ~0.05% with an optimized oligonucleotide design combining modified bases and reduced number of phosphorothioate bonds. We provide evidence from comparative RNA-seq analysis suggesting cellular immunity induced by the oligonucleotides might contribute to the low viability of oligo-corrected cells. Further optimization of this method should allow rapid and scalable genome engineering in human cells. PMID:22615794

MRI non-uniformity correction through interleaved bias estimation and B-spline deformation with a template.

PubMed

Fletcher, E; Carmichael, O; Decarli, C

2012-01-01

We propose a template-based method for correcting field inhomogeneity biases in magnetic resonance images (MRI) of the human brain. At each algorithm iteration, the update of a B-spline deformation between an unbiased template image and the subject image is interleaved with estimation of a bias field based on the current template-to-image alignment. The bias field is modeled using a spatially smooth thin-plate spline interpolation based on ratios of local image patch intensity means between the deformed template and subject images. This is used to iteratively correct subject image intensities which are then used to improve the template-to-image deformation. Experiments on synthetic and real data sets of images with and without Alzheimer's disease suggest that the approach may have advantages over the popular N3 technique for modeling bias fields and narrowing intensity ranges of gray matter, white matter, and cerebrospinal fluid. This bias field correction method has the potential to be more accurate than correction schemes based solely on intrinsic image properties or hypothetical image intensity distributions.

MRI Non-Uniformity Correction Through Interleaved Bias Estimation and B-Spline Deformation with a Template*

PubMed Central

Fletcher, E.; Carmichael, O.; DeCarli, C.

2013-01-01

We propose a template-based method for correcting field inhomogeneity biases in magnetic resonance images (MRI) of the human brain. At each algorithm iteration, the update of a B-spline deformation between an unbiased template image and the subject image is interleaved with estimation of a bias field based on the current template-to-image alignment. The bias field is modeled using a spatially smooth thin-plate spline interpolation based on ratios of local image patch intensity means between the deformed template and subject images. This is used to iteratively correct subject image intensities which are then used to improve the template-to-image deformation. Experiments on synthetic and real data sets of images with and without Alzheimer’s disease suggest that the approach may have advantages over the popular N3 technique for modeling bias fields and narrowing intensity ranges of gray matter, white matter, and cerebrospinal fluid. This bias field correction method has the potential to be more accurate than correction schemes based solely on intrinsic image properties or hypothetical image intensity distributions. PMID:23365843

Efficacy and workload analysis of a fixed vertical couch position technique and a fixed‐action–level protocol in whole‐breast radiotherapy

PubMed Central

Verhoeven, Karolien; Weltens, Caroline; Van den Heuvel, Frank

2015-01-01

Quantification of the setup errors is vital to define appropriate setup margins preventing geographical misses. The no‐action–level (NAL) correction protocol reduces the systematic setup errors and, hence, the setup margins. The manual entry of the setup corrections in the record‐and‐verify software, however, increases the susceptibility of the NAL protocol to human errors. Moreover, the impact of the skin mobility on the anteroposterior patient setup reproducibility in whole‐breast radiotherapy (WBRT) is unknown. In this study, we therefore investigated the potential of fixed vertical couch position‐based patient setup in WBRT. The possibility to introduce a threshold for correction of the systematic setup errors was also explored. We measured the anteroposterior, mediolateral, and superior–inferior setup errors during fractions 1–12 and weekly thereafter with tangential angled single modality paired imaging. These setup data were used to simulate the residual setup errors of the NAL protocol, the fixed vertical couch position protocol, and the fixed‐action–level protocol with different correction thresholds. Population statistics of the setup errors of 20 breast cancer patients and 20 breast cancer patients with additional regional lymph node (LN) irradiation were calculated to determine the setup margins of each off‐line correction protocol. Our data showed the potential of the fixed vertical couch position protocol to restrict the systematic and random anteroposterior residual setup errors to 1.8 mm and 2.2 mm, respectively. Compared to the NAL protocol, a correction threshold of 2.5 mm reduced the frequency of mediolateral and superior–inferior setup corrections with 40% and 63%, respectively. The implementation of the correction threshold did not deteriorate the accuracy of the off‐line setup correction compared to the NAL protocol. The combination of the fixed vertical couch position protocol, for correction of the anteroposterior setup error, and the fixed‐action–level protocol with 2.5 mm correction threshold, for correction of the mediolateral and the superior–inferior setup errors, was proved to provide adequate and comparable patient setup accuracy in WBRT and WBRT with additional LN irradiation. PACS numbers: 87.53.Kn, 87.57.‐s

Evaluation of repetitive extragenic palindromic-PCR for discrimination of fecal Escherichia coli from humans, and different domestic- and wild-animals.

PubMed

Mohapatra, Bidyut R; Broersma, Klaas; Nordin, Rick; Mazumder, Asit

2007-01-01

The objective of this study was to investigate the potential of repetitive extragenic palindromic anchored polymerase chain reaction (rep-PCR) in differentiating fecal Escherichia coli isolates of human, domestic- and wild-animal origin that might be used as a molecular tool to identify the possible source(s) of fecal pollution of source water. A total of 625 fecal E. coli isolates of human, 3 domestic- (cow, dog and horse) and 7 wild-animal (black bear, coyote, elk, marmot, mule deer, raccoon and wolf) species were characterized by rep-PCR DNA fingerprinting technique coupled with BOX A1R primer and discriminant analysis. Discriminant analysis of rep-PCR DNA fingerprints of fecal E. coli isolates from 11 host sources revealed an average rate of correct classification of 79.89%, and 84.6%, 83.8%, 83.3%, 82.5%, 81.6%, 80.8%, 79.8%, 79.3%, 77.4%, 73.2% and 63.6% of elk, human, marmot, mule deer, cow, coyote, raccoon, horse, dog, wolf and black bear fecal E. coli isolates were assigned to the correct host source. These results suggest that rep-PCR DNA fingerprinting procedures can be used as a source tracking tool for detection of human- as well as animal-derived fecal contamination of water.

The Success of Linear Bootstrapping Models: Decision Domain-, Expertise-, and Criterion-Specific Meta-Analysis

PubMed Central

Kaufmann, Esther; Wittmann, Werner W.

2016-01-01

The success of bootstrapping or replacing a human judge with a model (e.g., an equation) has been demonstrated in Paul Meehl’s (1954) seminal work and bolstered by the results of several meta-analyses. To date, however, analyses considering different types of meta-analyses as well as the potential dependence of bootstrapping success on the decision domain, the level of expertise of the human judge, and the criterion for what constitutes an accurate decision have been missing from the literature. In this study, we addressed these research gaps by conducting a meta-analysis of lens model studies. We compared the results of a traditional (bare-bones) meta-analysis with findings of a meta-analysis of the success of bootstrap models corrected for various methodological artifacts. In line with previous studies, we found that bootstrapping was more successful than human judgment. Furthermore, bootstrapping was more successful in studies with an objective decision criterion than in studies with subjective or test score criteria. We did not find clear evidence that the success of bootstrapping depended on the decision domain (e.g., education or medicine) or on the judge’s level of expertise (novice or expert). Correction of methodological artifacts increased the estimated success of bootstrapping, suggesting that previous analyses without artifact correction (i.e., traditional meta-analyses) may have underestimated the value of bootstrapping models. PMID:27327085

Universal Power Law Governing Pedestrian Interactions

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

Karamouzas, Ioannis; Skinner, Brian; Guy, Stephen J.

2014-12-01

Human crowds often bear a striking resemblance to interacting particle systems, and this has prompted many researchers to describe pedestrian dynamics in terms of interaction forces and potential energies. The correct quantitative form of this interaction, however, has remained an open question. Here, we introduce a novel statistical-mechanical approach to directly measure the interaction energy between pedestrians. This analysis, when applied to a large collection of human motion data, reveals a simple power-law interaction that is based not on the physical separation between pedestrians but on their projected time to a potential future collision, and is therefore fundamentally anticipatory inmore » nature. Remarkably, this simple law is able to describe human interactions across a wide variety of situations, speeds, and densities. We further show, through simulations, that the interaction law we identify is sufficient to reproduce many known crowd phenomena.« less

Protection of human muscle acetylcholinesterase from soman by pyridostigmine bromide.

PubMed

Maselli, Ricardo A; Henderson, John D; Ng, Jarae; Follette, David; Graves, Gregory; Wilson, Barry W

2011-04-01

Pretreatment with pyridostigmine bromide (PB) of human intercostal muscle fibers exposed to the irreversible acetylcholinesterase (AChE) inhibitor soman was investigated. Muscles were pretreated with 3 × 10(-6) M PB or saline for 20 minutes, then exposed to 10(-7) M soman for 10 minutes. AChE of muscles treated with soman alone was inhibited >95%. In contrast, PB pretreatment of soman-exposed bundles protected 20% of AChE activity. AChE of bundles exposed to PB alone recovered after 4 hours, but bundles exposed to both PB and soman did not. Soman-induced reduction of resting membrane potentials and increment of amplitudes and decay times of miniature endplate potentials (MEPPs) were partially corrected by PB pretreatment. In vitro pretreatment of human muscles with PB protected up to 20% of muscle AChE and ameliorated some deleterious effects on endplate physiology induced by soman. Copyright © 2011 Wiley Periodicals, Inc.

Metabolomics to Explore Impact of Dairy Intake

PubMed Central

Zheng, Hong; Clausen, Morten R.; Dalsgaard, Trine K.; Bertram, Hanne C.

2015-01-01

Dairy products are an important component in the Western diet and represent a valuable source of nutrients for humans. However, a reliable dairy intake assessment in nutrition research is crucial to correctly elucidate the link between dairy intake and human health. Metabolomics is considered a potential tool for assessment of dietary intake instead of traditional methods, such as food frequency questionnaires, food records, and 24-h recalls. Metabolomics has been successfully applied to discriminate between consumption of different dairy products under different experimental conditions. Moreover, potential metabolites related to dairy intake were identified, although these metabolites need to be further validated in other intervention studies before they can be used as valid biomarkers of dairy consumption. Therefore, this review provides an overview of metabolomics for assessment of dairy intake in order to better clarify the role of dairy products in human nutrition and health. PMID:26091233

75 FR 5536 - Pipeline Safety: Control Room Management/Human Factors, Correction

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-03

... DEPARTMENT OF TRANSPORTATION Pipeline and Hazardous Materials Safety Administration 49 CFR Parts...: Control Room Management/Human Factors, Correction AGENCY: Pipeline and Hazardous Materials Safety... following correcting amendments: PART 192--TRANSPORTATION OF NATURAL AND OTHER GAS BY PIPELINE: MINIMUM...

Choice of saccade endpoint under risk

PubMed Central

Ackermann, John F.; Landy, Michael S.

2013-01-01

Eye movements function to bring detailed information onto the high-resolution region of the retina. Previous research has shown that human observers select fixation points that maximize information acquisition and minimize target location uncertainty. In this study, we ask whether human observers choose the saccade endpoint that maximizes gain when there are explicit rewards associated with correctly detecting the target. Observers performed an 8-alternative forced-choice detection task for a contrast-defined target in noise. After a single saccade, observers indicated the target location. Each potential target location had an associated reward that was known to the observer. In some conditions, the reward at one location was higher than at the other locations. We compared human saccade endpoints to those of an ideal observer that maximizes expected gain given the respective human observer's visibility map, i.e., d′ for target detection as a function of retinal location. Varying the location of the highest reward had a significant effect on human observers' distribution of saccade endpoints. Both human and ideal observers show a high density of saccades made toward the highest rewarded and actual target locations. But humans' overall spatial distributions of saccade endpoints differed significantly from the ideal observer as they made a greater number of saccade to locations far from the highest rewarded and actual target locations. Suboptimal choice of saccade endpoint, possibly in combination with suboptimal integration of information across saccades, had a significant effect on human observers' ability to correctly detect the target and maximize gain. PMID:24023277

CORRRECTIVE ACTION DECISION DOCUMENT FOR CORRECTIVE ACTION UNIT 427: AREA 3 SEPTIC WASTE SYSTEMS 2 AND 6, TONOPAH TEST RANGE, NEVADA, REVISION 0, JUNE 1998

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

ITLV.

1998-06-01

This Corrective Action Decision Document has been prepared for the Area 3 Septic Waste Systems 2 and 6 (Corrective Action Unit 427) in accordance with the Federal Facility Agreement and Consent Order of 1996 (FFACO, 1996). Corrective Action Unit 427 is located at the Tonopah Test Range, Nevada, and is comprised of the following Corrective Action Sites, each an individual septic waste system (DOE/NV, 1996a): Septic Waste System 2 is Corrective Action Site Number 03-05-002-SW02. Septic Waste System 6 is Corrective Action Site Number 03-05-002-SW06. The purpose of this Corrective Action Decision Document is to identify and provide a rationalemore » for the selection of a recommended corrective action alternative for each Corrective Action Site. The scope of this Correction Action Decision Document consists of the following tasks: Develop corrective action objectives. Identify corrective action alternative screening criteria. Develop corrective action alternatives. Perform detailed and comparative evaluations of the corrective action alternatives in relation to the corrective action objectives and screening criteria. Recommend and justify a preferred corrective action alternative for each CAS. From November 1997 through January 1998, a corrective action investigation was performed as set forth in the Corrective Action Investigation Plan for Corrective Action Unit No. 427: Area 3 Septic Waste System Numbers 2 and 6, Tonopah Test Range, Nevada (DOE/NV, 1997b). Details can be found in Appendix A of this document. The results indicated that contamination is present in some portions of the CAU and not in others as described in Table ES-1 and shown in Figure A.2-2 of Appendix A. Based on the potential exposure pathways, the following corrective action objectives have been identified for Corrective Action Unit 427: Prevent or mitigate human exposure to subsurface soils containing TPH at concentrations greater than 100 milligrams per kilogram (NAC, 1996b). Close Septic Tank 33-5 in accordance with Nevada Administrative Code 459 (NAC, 1996c). Prevent adverse impacts to groundwater quality. Based on the review of existing data, future land use, and current operations at the Tonopah Test Range, the following alternatives were developed for consideration at the Area 3 Septic Waste Systems 2 and 6: Alternative 1 - No Further Action Alternative 2 - Closure of Septic Tank 33-5 and Administrative Controls Alternative 3 - Closure of Septic Tank 33-5, Excavation, and Disposal The corrective action alternatives were evaluated based on four general corrective action standards and five remedy selection decision factors. Based on the results of this evaluation, the preferred alternative for Corrective Action Unit 427 is Alternative 2, Closure of Septic Tank 33-5 and Administrative Controls. The preferred corrective action alternative was evaluated on technical merit, focusing on performance, reliability, feasibility, and safety. The alternative was judged to meet all requirements for the technical components evaluated. The alternative meets all applicable state and federal regulations for closure of the site and will reduce potential future exposure pathways to the contaminated soils. During corrective action implementation, this alternative will present minimal potential threat to site workers who come in contact with the waste. However, procedures will be developed and implemented to ensure worker health and safety.« less

Selenium Potentiates Chemotherapeutic Selectivity: Improving Efficacy and Reducing Toxicity

DTIC Science & Technology

2008-04-01

C., et al., Genetic correction of DNA repair-deficient/cancer- prone xeroderma pigmentosum group C keratinocytes. Hum Gene Ther, 2003. 14(10): p...983-96. 4. Muotri, A.R., et al., Complementation of the DNA repair deficiency in human xeroderma pigmentosum group a and C cells by recombinant...survival Keywords: DNA-repair, carboplatin, cisplatin, myelosuppression Abbreviations: Xpc, protein encoded by the xeroderma pigmentosum XPC

Retinal image contrast obtained by a model eye with combined correction of chromatic and spherical aberrations

PubMed Central

Ohnuma, Kazuhiko; Kayanuma, Hiroyuki; Lawu, Tjundewo; Negishi, Kazuno; Yamaguchi, Takefumi; Noda, Toru

2011-01-01

Correcting spherical and chromatic aberrations in vitro in human eyes provides substantial visual acuity and contrast sensitivity improvements. We found the same improvement in the retinal images using a model eye with/without correction of longitudinal chromatic aberrations (LCAs) and spherical aberrations (SAs). The model eye included an intraocular lens (IOL) and artificial cornea with human ocular LCAs and average human SAs. The optotypes were illuminated using a D65 light source, and the images were obtained using two-dimensional luminance colorimeter. The contrast improvement from the SA correction was higher than the LCA correction, indicating the benefit of an aspheric achromatic IOL. PMID:21698008

21 CFR 120.10 - Corrective actions.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 2 2013-04-01 2013-04-01 false Corrective actions. 120.10 Section 120.10 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION HAZARD ANALYSIS AND CRITICAL CONTROL POINT (HACCP) SYSTEMS General Provisions § 120.10 Corrective...

21 CFR 120.10 - Corrective actions.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 2 2011-04-01 2011-04-01 false Corrective actions. 120.10 Section 120.10 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION HAZARD ANALYSIS AND CRITICAL CONTROL POINT (HACCP) SYSTEMS General Provisions § 120.10 Corrective...

21 CFR 120.10 - Corrective actions.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 2 2012-04-01 2012-04-01 false Corrective actions. 120.10 Section 120.10 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION HAZARD ANALYSIS AND CRITICAL CONTROL POINT (HACCP) SYSTEMS General Provisions § 120.10 Corrective...

21 CFR 120.10 - Corrective actions.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 2 2014-04-01 2014-04-01 false Corrective actions. 120.10 Section 120.10 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION HAZARD ANALYSIS AND CRITICAL CONTROL POINT (HACCP) SYSTEMS General Provisions § 120.10 Corrective...

Eighteen- and 24-Month-Old Infants Correct Others in Anticipation of Action Mistakes

ERIC Educational Resources Information Center

Knudsen, Birgit; Liszkowski, Ulf

2012-01-01

Much of human communication and collaboration is predicated on making predictions about others' actions. Humans frequently use predictions about others' action mistakes to correct others and spare them mistakes. Such anticipatory correcting reveals a social motivation for unsolicited helping. Cognitively, it requires forward inferences about…

[Do media reports and public brochures facilitate informed decision making about cervical cancer prevention?].

PubMed

Neumeyer-Gromen, A; Bodemer, N; Müller, S M; Gigerenzer, G

2011-11-01

With the introduction and recommendation of the new HPV (human papillomavirus) vaccination in 2007, cervical cancer prevention has evoked large public interest. Is the public able to make informed decisions on the basis of media reports and brochures? To answer this question, an analysis of media coverage of HPV vaccination (Gardasil®) and Pap (Papanicolaou) screening was conducted from 2007-2009, which investigated the minimum requirement of completeness (pros and cons), transparency (absolute numbers), and correctness (references concerning outcome, uncertainty, magnitude) of the information. As a bench mark, facts boxes with concise data on epidemiology, etiology, benefits, harms, and costs were compiled in advance. Although all vaccination reports and brochures covered the impact of prevention, only 41% provided concrete numbers on effectiveness (90/220) and 2% on absolute risk reductions for the cancer surrogate dysplasia (5/220), whereby none of the latter numbers was correct. The prevention potential was correctly presented once. Only 48% (105/220) mentioned pros and cons. With regard to screening, 20% (4/20) provided explicit data on test quality and one expressed these in absolute numbers, while 25% (5/20) reported the prevention potential; all given numbers were correct. Finally, 25% (5/20) mentioned the possibility of false positive results. Minimum requirements were fulfilled by 1/220 vaccination and 1/20 screening reports. At present, informed decision making based on media coverage is hardly possible.

Corrective Action Investigation Plan for Corrective Action Unit 555: Septic Systems Nevada Test Site, Nevada, Rev. No.: 0 with Errata

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

Pastor, Laura

2005-12-01

This Corrective Action Investigation Plan (CAIP) contains project-specific information including facility descriptions, environmental sample collection objectives, and criteria for conducting site investigation activities at Corrective Action Unit (CAU) 555: Septic Systems, Nevada Test Site (NTS), Nevada. This CAIP has been developed in accordance with the ''Federal Facility Agreement and Consent Order'' (FFACO) (1996) that was agreed to by the State of Nevada, the U.S. Department of Energy (DOE), and the U.S. Department of Defense. Corrective Action Unit 555 is located in Areas 1, 3 and 6 of the NTS, which is approximately 65 miles (mi) northwest of Las Vegas, Nevada,more » and is comprised of the five corrective action sites (CASs) shown on Figure 1-1 and listed below: (1) CAS 01-59-01, Area 1 Camp Septic System; (2) CAS 03-59-03, Core Handling Building Septic System; (3) CAS 06-20-05, Birdwell Dry Well; (4) CAS 06-59-01, Birdwell Septic System; and (5) CAS 06-59-02, National Cementers Septic System. An FFACO modification was approved on December 14, 2005, to include CAS 06-20-05, Birdwell Dry Well, as part of the scope of CAU 555. The work scope was expanded in this document to include the investigation of CAS 06-20-05. The Corrective Action Investigation (CAI) will include field inspections, radiological surveys, geophysical surveys, sampling of environmental media, analysis of samples, and assessment of investigation results, where appropriate. Data will be obtained to support corrective action alternative evaluations and waste management decisions. The CASs in CAU 555 are being investigated because hazardous and/or radioactive constituents may be present in concentrations that could potentially pose a threat to human health and the environment. Existing information on the nature and extent of potential contamination is insufficient to evaluate and recommend corrective action alternatives for the CASs. Additional information will be generated by conducting a CAI before the evaluation and selection of corrective action alternatives.« less

Age-related decline in ovarian follicle stocks differ between chimpanzees (Pan troglodytes) and humans.

PubMed

Cloutier, Christina T; Coxworth, James E; Hawkes, Kristen

2015-02-01

Similarity in oldest parturitions in humans and great apes suggests that we maintain ancestral rates of ovarian aging. Consistent with that hypothesis, previous counts of primordial follicles in postmortem ovarian sections from chimpanzees (Pan troglodytes) showed follicle stock decline at the same rate that human stocks decline across the same ages. Here, we correct that finding with a chimpanzee sample more than three times larger than the previous one, which also allows comparison into older ages. Analyses show depletion rates similar until about age 35, but after 35, the human counts continue to fall with age, while the change is much less steep in chimpanzees. This difference implicates likely effects on ovarian dynamics from other physiological systems that are senescing at different rates, and, potentially, different perimenopausal experience for chimpanzees and humans.

Using Human Induced Pluripotent Stem Cells to Model Skeletal Diseases.

PubMed

Barruet, Emilie; Hsiao, Edward C

2016-01-01

Musculoskeletal disorders affecting the bones and joints are major health problems among children and adults. Major challenges such as the genetic origins or poor diagnostics of severe skeletal disease hinder our understanding of human skeletal diseases. The recent advent of human induced pluripotent stem cells (human iPS cells) provides an unparalleled opportunity to create human-specific models of human skeletal diseases. iPS cells have the ability to self-renew, allowing us to obtain large amounts of starting material, and have the potential to differentiate into any cell types in the body. In addition, they can carry one or more mutations responsible for the disease of interest or be genetically corrected to create isogenic controls. Our work has focused on modeling rare musculoskeletal disorders including fibrodysplasia ossificans progressive (FOP), a congenital disease of increased heterotopic ossification. In this review, we will discuss our experiences and protocols differentiating human iPS cells toward the osteogenic lineage and their application to model skeletal diseases. A number of critical challenges and exciting new approaches are also discussed, which will allow the skeletal biology field to harness the potential of human iPS cells as a critical model system for understanding diseases of abnormal skeletal formation and bone regeneration.

Understanding human management of automation errors

PubMed Central

McBride, Sara E.; Rogers, Wendy A.; Fisk, Arthur D.

2013-01-01

Automation has the potential to aid humans with a diverse set of tasks and support overall system performance. Automated systems are not always reliable, and when automation errs, humans must engage in error management, which is the process of detecting, understanding, and correcting errors. However, this process of error management in the context of human-automation interaction is not well understood. Therefore, we conducted a systematic review of the variables that contribute to error management. We examined relevant research in human-automation interaction and human error to identify critical automation, person, task, and emergent variables. We propose a framework for management of automation errors to incorporate and build upon previous models. Further, our analysis highlights variables that may be addressed through design and training to positively influence error management. Additional efforts to understand the error management process will contribute to automation designed and implemented to support safe and effective system performance. PMID:25383042

Understanding human management of automation errors.

PubMed

McBride, Sara E; Rogers, Wendy A; Fisk, Arthur D

2014-01-01

Automation has the potential to aid humans with a diverse set of tasks and support overall system performance. Automated systems are not always reliable, and when automation errs, humans must engage in error management, which is the process of detecting, understanding, and correcting errors. However, this process of error management in the context of human-automation interaction is not well understood. Therefore, we conducted a systematic review of the variables that contribute to error management. We examined relevant research in human-automation interaction and human error to identify critical automation, person, task, and emergent variables. We propose a framework for management of automation errors to incorporate and build upon previous models. Further, our analysis highlights variables that may be addressed through design and training to positively influence error management. Additional efforts to understand the error management process will contribute to automation designed and implemented to support safe and effective system performance.

Attenuation correction for the large non-human primate brain imaging using microPET.

PubMed

Naidoo-Variawa, S; Lehnert, W; Kassiou, M; Banati, R; Meikle, S R

2010-04-21

Assessment of the biodistribution and pharmacokinetics of radiopharmaceuticals in vivo is often performed on animal models of human disease prior to their use in humans. The baboon brain is physiologically and neuro-anatomically similar to the human brain and is therefore a suitable model for evaluating novel CNS radioligands. We previously demonstrated the feasibility of performing baboon brain imaging on a dedicated small animal PET scanner provided that the data are accurately corrected for degrading physical effects such as photon attenuation in the body. In this study, we investigated factors affecting the accuracy and reliability of alternative attenuation correction strategies when imaging the brain of a large non-human primate (papio hamadryas) using the microPET Focus 220 animal scanner. For measured attenuation correction, the best bias versus noise performance was achieved using a (57)Co transmission point source with a 4% energy window. The optimal energy window for a (68)Ge transmission source operating in singles acquisition mode was 20%, independent of the source strength, providing bias-noise performance almost as good as for (57)Co. For both transmission sources, doubling the acquisition time had minimal impact on the bias-noise trade-off for corrected emission images, despite observable improvements in reconstructed attenuation values. In a [(18)F]FDG brain scan of a female baboon, both measured attenuation correction strategies achieved good results and similar SNR, while segmented attenuation correction (based on uncorrected emission images) resulted in appreciable regional bias in deep grey matter structures and the skull. We conclude that measured attenuation correction using a single pass (57)Co (4% energy window) or (68)Ge (20% window) transmission scan achieves an excellent trade-off between bias and propagation of noise when imaging the large non-human primate brain with a microPET scanner.

Attenuation correction for the large non-human primate brain imaging using microPET

NASA Astrophysics Data System (ADS)

Naidoo-Variawa, S.; Lehnert, W.; Kassiou, M.; Banati, R.; Meikle, S. R.

2010-04-01

Assessment of the biodistribution and pharmacokinetics of radiopharmaceuticals in vivo is often performed on animal models of human disease prior to their use in humans. The baboon brain is physiologically and neuro-anatomically similar to the human brain and is therefore a suitable model for evaluating novel CNS radioligands. We previously demonstrated the feasibility of performing baboon brain imaging on a dedicated small animal PET scanner provided that the data are accurately corrected for degrading physical effects such as photon attenuation in the body. In this study, we investigated factors affecting the accuracy and reliability of alternative attenuation correction strategies when imaging the brain of a large non-human primate (papio hamadryas) using the microPET Focus 220 animal scanner. For measured attenuation correction, the best bias versus noise performance was achieved using a 57Co transmission point source with a 4% energy window. The optimal energy window for a 68Ge transmission source operating in singles acquisition mode was 20%, independent of the source strength, providing bias-noise performance almost as good as for 57Co. For both transmission sources, doubling the acquisition time had minimal impact on the bias-noise trade-off for corrected emission images, despite observable improvements in reconstructed attenuation values. In a [18F]FDG brain scan of a female baboon, both measured attenuation correction strategies achieved good results and similar SNR, while segmented attenuation correction (based on uncorrected emission images) resulted in appreciable regional bias in deep grey matter structures and the skull. We conclude that measured attenuation correction using a single pass 57Co (4% energy window) or 68Ge (20% window) transmission scan achieves an excellent trade-off between bias and propagation of noise when imaging the large non-human primate brain with a microPET scanner.

Basic mechanism for biorientation of mitotic chromosomes is provided by the kinetochore geometry and indiscriminate turnover of kinetochore microtubules

PubMed Central

Zaytsev, Anatoly V.; Grishchuk, Ekaterina L.

2015-01-01

Accuracy of chromosome segregation relies on the ill-understood ability of mitotic kinetochores to biorient, whereupon each sister kinetochore forms microtubule (MT) attachments to only one spindle pole. Because initial MT attachments result from chance encounters with the kinetochores, biorientation must rely on specific mechanisms to avoid and resolve improper attachments. Here we use mathematical modeling to critically analyze the error-correction potential of a simplified biorientation mechanism, which involves the back-to-back arrangement of sister kinetochores and the marked instability of kinetochore–MT attachments. We show that a typical mammalian kinetochore operates in a near-optimal regime, in which the back-to-back kinetochore geometry and the indiscriminate kinetochore–MT turnover provide strong error-correction activity. In human cells, this mechanism alone can potentially enable normal segregation of 45 out of 46 chromosomes during one mitotic division, corresponding to a mis-segregation rate in the range of 10−1–10−2 per chromosome. This theoretical upper limit for chromosome segregation accuracy predicted with the basic mechanism is close to the mis-segregation rate in some cancer cells; however, it cannot explain the relatively low chromosome loss in diploid human cells, consistent with their reliance on additional mechanisms. PMID:26424798

Corrective Action Investigation Plan for Corrective Action Unit 516: Septic Systems and Discharge Points, Nevada Test Site, Nevada, Rev. 0, Including Record of Technical Change No. 1

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

None

This Corrective Action Investigation Plan (CAIP) contains the U.S. Department of Energy (DOE), National Nuclear Security Administration Nevada Sites Office's (NNSA/NSO's) approach to collect the data necessary to evaluate corrective action alternatives appropriate for the closure of Corrective Action Unit (CAU) 516, Septic Systems and Discharge Points, Nevada Test Site (NTS), Nevada, under the Federal Facility Agreement and Consent Order. CAU 516 consists of six Corrective Action Sites: 03-59-01, Building 3C-36 Septic System; 03-59-02, Building 3C-45 Septic System; 06-51-01, Sump Piping, 06-51-02, Clay Pipe and Debris; 06-51-03, Clean Out Box and Piping; and 22-19-04, Vehicle Decontamination Area. Located in Areasmore » 3, 6, and 22 of the NTS, CAU 516 is being investigated because disposed waste may be present without appropriate controls, and hazardous and/or radioactive constituents may be present or migrating at concentrations and locations that could potentially pose a threat to human health and the environment. Existing information and process knowledge on the expected nature and extent of contamination of CAU 516 are insufficient to select preferred corrective action alternatives; therefore, additional information will be obtained by conducting a corrective action investigation. The results of this field investigation will support a defensible evaluation of corrective action alternatives in the corrective action decision document. Record of Technical Change No. 1 is dated 3/2004.« less

Prediction of preservative sensitization potential using surface marker CD86 and/or CD54 expression on human cell line, THP-1.

PubMed

Sakaguchi, Hitoshi; Miyazawa, Masaaki; Yoshida, Yukiko; Ito, Yuichi; Suzuki, Hiroyuki

2007-02-01

Preservatives are important components in many products, but have a history of purported allergy. Several assays [e.g., guinea pig maximization test (GPMT), local lymph node assay (LLNA)] are used to evaluate allergy potential of preservatives. We recently developed the human Cell Line Activation Test (h-CLAT), an in vitro skin sensitization test using human THP-1 cells. This test evaluates the augmentation of CD86 and CD54 expression, which are key events in the sensitization process, as an indicator of allergy following treatment with test chemical. Earlier, we found that a sub-toxic concentration was needed for the up-regulation of surface marker expression. In this study, we further evaluate the capability of h-CLAT to predict allergy potential using eight preservatives. Cytotoxicity was determined using propidium iodide with flow cytometry analysis and five doses that produce a 95, 85, 75, 65, and 50% cell viability were selected. If a material did not have any cytotoxicity at the highest technical dose (HTD), five doses are set using serial 1.3 dilutions of the HTD. The test materials used were six known allergic preservatives (e.g., methylchloroisothiazolinone/methylisothiazolinone, formaldehyde), and two non-allergic preservatives (methylparaben and 4-hydroxybenzoic acid). All allergic preservatives augmented CD86 and/or CD54 expression, indicating h-CLAT correctly identified the allergens. No augmentation was observed with the non-allergic preservatives; also correctly identified by h-CLAT. In addition, we report two threshold concentrations that may be used to categorize skin sensitization potency like the LLNA estimated concentration that yield a three-fold stimulation (EC3) value. These corresponding values are the estimated concentration which gives a relative fluorescence intensity (RFI) = 150 for CD86 and an RFI = 200 for CD54. These data suggest that h-CLAT, using THP-1 cells, may be able to predict the allergy potential of preservatives and possibility classify the potency of an allergen.

Combining EEG and eye tracking: identification, characterization, and correction of eye movement artifacts in electroencephalographic data

PubMed Central

Plöchl, Michael; Ossandón, José P.; König, Peter

2012-01-01

Eye movements introduce large artifacts to electroencephalographic recordings (EEG) and thus render data analysis difficult or even impossible. Trials contaminated by eye movement and blink artifacts have to be discarded, hence in standard EEG-paradigms subjects are required to fixate on the screen. To overcome this restriction, several correction methods including regression and blind source separation have been proposed. Yet, there is no automated standard procedure established. By simultaneously recording eye movements and 64-channel-EEG during a guided eye movement paradigm, we investigate and review the properties of eye movement artifacts, including corneo-retinal dipole changes, saccadic spike potentials and eyelid artifacts, and study their interrelations during different types of eye- and eyelid movements. In concordance with earlier studies our results confirm that these artifacts arise from different independent sources and that depending on electrode site, gaze direction, and choice of reference these sources contribute differently to the measured signal. We assess the respective implications for artifact correction methods and therefore compare the performance of two prominent approaches, namely linear regression and independent component analysis (ICA). We show and discuss that due to the independence of eye artifact sources, regression-based correction methods inevitably over- or under-correct individual artifact components, while ICA is in principle suited to address such mixtures of different types of artifacts. Finally, we propose an algorithm, which uses eye tracker information to objectively identify eye-artifact related ICA-components (ICs) in an automated manner. In the data presented here, the algorithm performed very similar to human experts when those were given both, the topographies of the ICs and their respective activations in a large amount of trials. Moreover it performed more reliable and almost twice as effective than human experts when those had to base their decision on IC topographies only. Furthermore, a receiver operating characteristic (ROC) analysis demonstrated an optimal balance of false positive and false negative at an area under curve (AUC) of more than 0.99. Removing the automatically detected ICs from the data resulted in removal or substantial suppression of ocular artifacts including microsaccadic spike potentials, while the relevant neural signal remained unaffected. In conclusion the present work aims at a better understanding of individual eye movement artifacts, their interrelations and the respective implications for eye artifact correction. Additionally, the proposed ICA-procedure provides a tool for optimized detection and correction of eye movement-related artifact components. PMID:23087632

Fiber-based polarization-sensitive OCT of the human retina with correction of system polarization distortions

PubMed Central

Braaf, Boy; Vermeer, Koenraad A.; de Groot, Mattijs; Vienola, Kari V.; de Boer, Johannes F.

2014-01-01

In polarization-sensitive optical coherence tomography (PS-OCT) the use of single-mode fibers causes unpredictable polarization distortions which can result in increased noise levels and erroneous changes in calculated polarization parameters. In the current paper this problem is addressed by a new Jones matrix analysis method that measures and corrects system polarization distortions as a function of wavenumber by spectral analysis of the sample surface polarization state and deeper located birefringent tissue structures. This method was implemented on a passive-component depth-multiplexed swept-source PS-OCT system at 1040 nm which was theoretically modeled using Jones matrix calculus. High-resolution B-scan images are presented of the double-pass phase retardation, diattenuation, and relative optic axis orientation to show the benefits of the new analysis method for in vivo imaging of the human retina. The correction of system polarization distortions yielded reduced phase retardation noise, and better estimates of the diattenuation and the relative optic axis orientation in weakly birefringent tissues. The clinical potential of the system is shown by en face visualization of the phase retardation and optic axis orientation of the retinal nerve fiber layer in a healthy volunteer and a glaucoma patient with nerve fiber loss. PMID:25136498

Minimizing human error in radiopharmaceutical preparation and administration via a bar code-enhanced nuclear pharmacy management system.

PubMed

Hakala, John L; Hung, Joseph C; Mosman, Elton A

2012-09-01

The objective of this project was to ensure correct radiopharmaceutical administration through the use of a bar code system that links patient and drug profiles with on-site information management systems. This new combined system would minimize the amount of manual human manipulation, which has proven to be a primary source of error. The most common reason for dosing errors is improper patient identification when a dose is obtained from the nuclear pharmacy or when a dose is administered. A standardized electronic transfer of information from radiopharmaceutical preparation to injection will further reduce the risk of misadministration. Value stream maps showing the flow of the patient dose information, as well as potential points of human error, were developed. Next, a future-state map was created that included proposed corrections for the most common critical sites of error. Transitioning the current process to the future state will require solutions that address these sites. To optimize the future-state process, a bar code system that links the on-site radiology management system with the nuclear pharmacy management system was proposed. A bar-coded wristband connects the patient directly to the electronic information systems. The bar code-enhanced process linking the patient dose with the electronic information reduces the number of crucial points for human error and provides a framework to ensure that the prepared dose reaches the correct patient. Although the proposed flowchart is designed for a site with an in-house central nuclear pharmacy, much of the framework could be applied by nuclear medicine facilities using unit doses. An electronic connection between information management systems to allow the tracking of a radiopharmaceutical from preparation to administration can be a useful tool in preventing the mistakes that are an unfortunate reality for any facility.

Corrective Action Investigation Plan for Corrective Action Unit 140: Waste Dumps, Burn Pits, and Storage Area, Nevada Test Site, Nevada, July 2002, Rev. No. 0

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

NNSA /NV

This Corrective Action Investigation Plan contains the U.S. Department of Energy, National Nuclear Security Administration Nevada Operations Office's approach to collect the data necessary to evaluate corrective action alternatives appropriate for the closure of Corrective Action Unit (CAU) 140 under the Federal Facility Agreement and Consent Order. Corrective Action Unit 140 consists of nine Corrective Action Sites (CASs): 05-08-01, Detonation Pits; 05-08-02, Debris Pits; 05-17-01, Hazardous Waste Accumulation Site (Buried); 05-19-01, Waste Disposal Site; 05-23-01, Gravel Gertie; 05-35-01, Burn Pit; 05-99-04, Burn Pit; 22-99-04, Radioactive Waste Dump; 23-17-01, Hazardous Waste Storage Area. All nine of these CASs are located withinmore » Areas 5, 22, and 23 of the Nevada Test Site (NTS) in Nevada, approximately 65 miles northwest of Las Vegas. This CAU is being investigated because disposed waste may be present without appropriate controls (i.e., use restrictions, adequate cover) and hazardous and/or radioactive constituents may be present or migrating at concentrations and locations that could potentially pose a threat to human health and the environment. The NTS has been used for various research and development projects including nuclear weapons testing. The CASs in CAU 140 were used for testing, material storage, waste storage, and waste disposal. A two-phase approach has been selected to collect information and generate data to satisfy needed resolution criteria and resolve the decision statements. Phase I will determine if contaminants of potential concern (COPCs) are present in concentrations exceeding preliminary action levels. This data will be evaluated at all CASs. Phase II will determine the extent of the contaminant(s) of concern (COCs). This data will only be evaluated for CASs with a COC identified during Phase I. Based on process knowledge, the COPCs for CAU 140 include volatile organics, semivolatile organics, petroleum hydrocarbons, explosive residues, herbicides, pesticides, polychlorinated biphenyls, metals, and radionuclides. The results of this field investigation will support a defensible evaluation of corrective action alternatives in the corrective action decision document.« less

Influence and Correction from the Human Body on the Measurement of a Power-Frequency Electric Field Sensor

PubMed Central

Xiao, Dongping; Liu, Huaitong; Zhou, Qiang; Xie, Yutong; Ma, Qichao

2016-01-01

According to the operating specifications of existing electric field measuring instruments, measuring technicians must be located far from the instruments to eliminate the influence of the human body occupancy on a spatial electric field. Nevertheless, in order to develop a portable safety protection instrument with an effective electric field warning function for working staff in a high-voltage environment, it is necessary to study the influence of an approaching human body on the measurement of an electric field and to correct the measurement results. A single-shaft electric field measuring instrument called the Type LP-2000, which was developed by our research team, is used as the research object in this study. First, we explain the principle of electric field measurement and describe the capacitance effect produced by the human body. Through a theoretical analysis, we show that the measured electric field value decreases as a human body approaches. Their relationship is linearly proportional. Then, the ratio is identified as a correction coefficient to correct for the influence of human body proximity. The conclusion drawn from the theoretical analysis is proved via simulation. The correction coefficient kb = 1.8010 is obtained on the basis of the linear fitting of simulated data. Finally, a physical experiment is performed. When no human is present, we compare the results from the Type LP-2000 measured with Narda EFA-300 and the simulated value to verify the accuracy of the Type LP-2000. For the case of an approaching human body, the correction coefficient kb* = 1.9094 is obtained by comparing the data measured with the Type LP-2000 to the simulated value. The correction coefficient obtained from the experiment (i.e., kb*) is highly consistent with that obtained from the simulation (i.e., kb). Two experimental programs are set; under these programs, the excitation voltages and distance measuring points are regulated to produce different electric field intensities. Using kb = 1.9094, the corrected measurement of electric field intensity can accurately reflect the original environmental electric field intensity, and the maximal error is less than 6% in all the data comparisons. These results verify the effectiveness of our proposed method. PMID:27294936

Influence and Correction from the Human Body on the Measurement of a Power-Frequency Electric Field Sensor.

PubMed

Xiao, Dongping; Liu, Huaitong; Zhou, Qiang; Xie, Yutong; Ma, Qichao

2016-06-10

According to the operating specifications of existing electric field measuring instruments, measuring technicians must be located far from the instruments to eliminate the influence of the human body occupancy on a spatial electric field. Nevertheless, in order to develop a portable safety protection instrument with an effective electric field warning function for working staff in a high-voltage environment, it is necessary to study the influence of an approaching human body on the measurement of an electric field and to correct the measurement results. A single-shaft electric field measuring instrument called the Type LP-2000, which was developed by our research team, is used as the research object in this study. First, we explain the principle of electric field measurement and describe the capacitance effect produced by the human body. Through a theoretical analysis, we show that the measured electric field value decreases as a human body approaches. Their relationship is linearly proportional. Then, the ratio is identified as a correction coefficient to correct for the influence of human body proximity. The conclusion drawn from the theoretical analysis is proved via simulation. The correction coefficient kb = 1.8010 is obtained on the basis of the linear fitting of simulated data. Finally, a physical experiment is performed. When no human is present, we compare the results from the Type LP-2000 measured with Narda EFA-300 and the simulated value to verify the accuracy of the Type LP-2000. For the case of an approaching human body, the correction coefficient kb* = 1.9094 is obtained by comparing the data measured with the Type LP-2000 to the simulated value. The correction coefficient obtained from the experiment (i.e., kb*) is highly consistent with that obtained from the simulation (i.e., kb). Two experimental programs are set; under these programs, the excitation voltages and distance measuring points are regulated to produce different electric field intensities. Using kb = 1.9094, the corrected measurement of electric field intensity can accurately reflect the original environmental electric field intensity, and the maximal error is less than 6% in all the data comparisons. These results verify the effectiveness of our proposed method.

Dysregulation of lysosomal morphology by pathogenic LRRK2 is corrected by TPC2 inhibition

PubMed Central

Hockey, Leanne N.; Kilpatrick, Bethan S.; Eden, Emily R.; Lin-Moshier, Yaping; Brailoiu, G. Cristina; Brailoiu, Eugen; Futter, Clare E.; Schapira, Anthony H.; Marchant, Jonathan S.; Patel, Sandip

2015-01-01

ABSTRACT Two-pore channels (TPCs) are endolysosomal ion channels implicated in Ca2+ signalling from acidic organelles. The relevance of these ubiquitous proteins for human disease, however, is unclear. Here, we report that lysosomes are enlarged and aggregated in fibroblasts from Parkinson disease patients with the common G2019S mutation in LRRK2. Defects were corrected by molecular silencing of TPC2, pharmacological inhibition of TPC regulators [Rab7, NAADP and PtdIns(3,5)P2] and buffering local Ca2+ increases. NAADP-evoked Ca2+ signals were exaggerated in diseased cells. TPC2 is thus a potential drug target within a pathogenic LRRK2 cascade that disrupts Ca2+-dependent trafficking in Parkinson disease. PMID:25416817

Induced Pluripotent Stem Cells in Dermatology: Potentials, Advances, and Limitations

PubMed Central

Bilousova, Ganna; Roop, Dennis R.

2014-01-01

The discovery of methods for reprogramming adult somatic cells into induced pluripotent stem cells (iPSCs) has raised the possibility of producing truly personalized treatment options for numerous diseases. Similar to embryonic stem cells (ESCs), iPSCs can give rise to any cell type in the body and are amenable to genetic correction by homologous recombination. These ESC properties of iPSCs allow for the development of permanent corrective therapies for many currently incurable disorders, including inherited skin diseases, without using embryonic tissues or oocytes. Here, we review recent progress and limitations of iPSC research with a focus on clinical applications of iPSCs and using iPSCs to model human diseases for drug discovery in the field of dermatology. PMID:25368014

76 FR 3134 - Human Studies Review Board; Notice of Public Meeting; Correction

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-19

... ENVIRONMENTAL PROTECTION AGENCY [EPA-HQ-ORD-2010-0970; FRL-9254-7] Human Studies Review Board; Notice of Public Meeting; Correction AGENCY: Environmental Protection Agency (EPA). ACTION: Notice... Register of January 12, 2011, announcing the January 26, 2011 public meeting of the Human Studies Review...

Indoor air quality investigation and health risk assessment at correctional institutions.

PubMed

Ofungwu, Joseph

2005-04-01

A comprehensive indoor air-quality (IAQ) investigation was conducted at a state correctional facility in New Jersey, USA with a lengthy history of IAQ problems. The IAQ investigation comprised preliminary indoor air screening using direct readout instrumentation, indoor air/surface wipe sampling and laboratory analysis, as well as a heating, ventilation, and air-conditioning system evaluation, and a building envelope survey. In addition to air sampling, a human health risk assessment was performed to evaluate the potential for exposure to site-related air contaminants with respect to the inmate and worker populations. The risk assessment results for the prison facility indicated the potential for significant health risks for the inmate population, possibly reflecting the effects of their confinement and extended exposure to indoor air contaminants, as compared to the prison guard and worker population. Based on the results of the risk assessment, several mitigation measures are recommended to minimize prison population health risks and improve indoor air quality at prison facilities.

Reversible Femtosecond Laser-Assisted Myopia Correction: A Non-Human Primate Study of Lenticule Re-Implantation after Refractive Lenticule Extraction

PubMed Central

Chaurasia, Shyam S.; Lee, Wing S.; Tan, Donald T.; Mehta, Jodhbir S.

2013-01-01

LASIK (laser-assisted in situ keratomileusis) is a common laser refractive procedure for myopia and astigmatism, involving permanent removal of anterior corneal stromal tissue by excimer ablation beneath a hinged flap. Correction of refractive error is achieved by the resulting change in the curvature of the cornea and is limited by central corneal thickness, as a thin residual stromal bed may result in biomechanical instability of the cornea. A recently developed alternative to LASIK called Refractive Lenticule Extraction (ReLEx) utilizes solely a femtosecond laser (FSL) to incise an intrastromal refractive lenticule (RL), which results in reshaping the corneal curvature and correcting the myopia and/or astigmatism. As the RL is extracted intact in the ReLEx, we hypothesized that it could be cryopreserved and re-implanted at a later date to restore corneal stromal volume, in the event of keratectasia, making ReLEx a potentially reversible procedure, unlike LASIK. In this study, we re-implanted cryopreserved RLs in a non-human primate model of ReLEx. Mild intrastromal haze, noted during the first 2 weeks after re-implantation, subsided after 8 weeks. Refractive parameters including corneal thickness, anterior curvature and refractive error indices were restored to near pre-operative values after the re-implantation. Immunohistochemistry revealed no myofibroblast formation or abnormal collagen type I expression after 8 weeks, and a significant attenuation of fibronectin and tenascin expression from week 8 to 16 after re-implantation. In addition, keratocyte re-population could be found along the implanted RL interfaces. Our findings suggest that RL cryopreservation and re-implantation after ReLEx appears feasible, suggesting the possibility of potential reversibility of the procedure, and possible future uses of RLs in treating other corneal disorders and refractive errors. PMID:23826194

Production of refolded Toxoplasma gondii recombinant SAG1-related sequence 3 (SRS3) and its use for serodiagnosis of human toxoplasmosis.

PubMed

Mirzadeh, Abolfazl; Saadatnia, Geita; Golkar, Majid; Babaie, Jalal; Noordin, Rahmah

2017-05-01

SAG1-related sequence 3 (SRS3) is one of the major Toxoplasma gondii tachyzoite surface antigens and has been shown to be potentially useful for the detection of toxoplasmosis. This protein is highly conformational due to the presence of six disulfide bonds. To achieve solubility and antigenicity, SRS3 depends on proper disulfide bond formation. The aim of this study was to over-express the SRS3 protein with correct folding for use in serodiagnosis of the disease. To achieve this, a truncated SRS3 fusion protein (rtSRS3) was produced, containing six histidyl residues at both terminals and purified by immobilized metal affinity chromatography. The refolding process was performed through three methods, namely dialysis in the presence of chemical additives along with reduced/oxidized glutathione and drop-wise dilution methods with reduced/oxidized glutathione or reduced DTT/oxidized glutathione. Ellman's assay and ELISA showed that the protein folding obtained by the dialysis method was the most favorable, probably due to the correct folding. Subsequently, serum samples from individuals with chronic infection (n = 76), probable acute infection (n = 14), and healthy controls (n = 81) were used to determine the usefulness of the refolded rtSRS3 for Toxoplasma serodiagnosis. The results of the developed IgG-ELISA showed a diagnostic specificity of 91% and a sensitivity of 82.89% and 100% for chronic and acute serum samples, respectively. In conclusion, correctly folded rtSRS3 has the potential to be used as a soluble antigen for the detection of human toxoplasmosis. Copyright © 2017 Elsevier Inc. All rights reserved.

MR-assisted PET Motion Correction for eurological Studies in an Integrated MR-PET Scanner

PubMed Central

Catana, Ciprian; Benner, Thomas; van der Kouwe, Andre; Byars, Larry; Hamm, Michael; Chonde, Daniel B.; Michel, Christian J.; El Fakhri, Georges; Schmand, Matthias; Sorensen, A. Gregory

2011-01-01

Head motion is difficult to avoid in long PET studies, degrading the image quality and offsetting the benefit of using a high-resolution scanner. As a potential solution in an integrated MR-PET scanner, the simultaneously acquired MR data can be used for motion tracking. In this work, a novel data processing and rigid-body motion correction (MC) algorithm for the MR-compatible BrainPET prototype scanner is described and proof-of-principle phantom and human studies are presented. Methods To account for motion, the PET prompts and randoms coincidences as well as the sensitivity data are processed in the line or response (LOR) space according to the MR-derived motion estimates. After sinogram space rebinning, the corrected data are summed and the motion corrected PET volume is reconstructed from these sinograms and the attenuation and scatter sinograms in the reference position. The accuracy of the MC algorithm was first tested using a Hoffman phantom. Next, human volunteer studies were performed and motion estimates were obtained using two high temporal resolution MR-based motion tracking techniques. Results After accounting for the physical mismatch between the two scanners, perfectly co-registered MR and PET volumes are reproducibly obtained. The MR output gates inserted in to the PET list-mode allow the temporal correlation of the two data sets within 0.2 s. The Hoffman phantom volume reconstructed processing the PET data in the LOR space was similar to the one obtained processing the data using the standard methods and applying the MC in the image space, demonstrating the quantitative accuracy of the novel MC algorithm. In human volunteer studies, motion estimates were obtained from echo planar imaging and cloverleaf navigator sequences every 3 seconds and 20 ms, respectively. Substantially improved PET images with excellent delineation of specific brain structures were obtained after applying the MC using these MR-based estimates. Conclusion A novel MR-based MC algorithm was developed for the integrated MR-PET scanner. High temporal resolution MR-derived motion estimates (obtained while simultaneously acquiring anatomical or functional MR data) can be used for PET MC. An MR-based MC has the potential to improve PET as a quantitative method, increasing its reliability and reproducibility which could benefit a large number of neurological applications. PMID:21189415

Human versus automation in responding to failures: an expected-value analysis

NASA Technical Reports Server (NTRS)

Sheridan, T. B.; Parasuraman, R.

2000-01-01

A simple analytical criterion is provided for deciding whether a human or automation is best for a failure detection task. The method is based on expected-value decision theory in much the same way as is signal detection. It requires specification of the probabilities of misses (false negatives) and false alarms (false positives) for both human and automation being considered, as well as factors independent of the choice--namely, costs and benefits of incorrect and correct decisions as well as the prior probability of failure. The method can also serve as a basis for comparing different modes of automation. Some limiting cases of application are discussed, as are some decision criteria other than expected value. Actual or potential applications include the design and evaluation of any system in which either humans or automation are being considered.

Gene Editing of Human Hematopoietic Stem and Progenitor Cells: Promise and Potential Hurdles.

PubMed

Yu, Kyung-Rok; Natanson, Hannah; Dunbar, Cynthia E

2016-10-01

Hematopoietic stem and progenitor cells (HSPCs) have great therapeutic potential because of their ability to both self-renew and differentiate. It has been proposed that, given their unique properties, a small number of genetically modified HSPCs could accomplish lifelong, corrective reconstitution of the entire hematopoietic system in patients with various hematologic disorders. Scientists have demonstrated that gene addition therapies-targeted to HSPCs and using integrating retroviral vectors-possess clear clinical benefits in multiple diseases, among them immunodeficiencies, storage disorders, and hemoglobinopathies. Scientists attempting to develop clinically relevant gene therapy protocols have, however, encountered a number of unexpected hurdles because of their incomplete knowledge of target cells, genomic control, and gene transfer technologies. Targeted gene-editing technologies using engineered nucleases such as ZFN, TALEN, and/or CRISPR/Cas9 RGEN show great clinical promise, allowing for the site-specific correction of disease-causing mutations-a process with important applications in autosomal dominant or dominant-negative genetic disorders. The relative simplicity of the CRISPR/Cas9 system, in particular, has sparked an exponential increase in the scientific community's interest in and use of these gene-editing technologies. In this minireview, we discuss the specific applications of gene-editing technologies in human HSPCs, as informed by prior experience with gene addition strategies. HSPCs are desirable but challenging targets; the specific mechanisms these cells evolved to protect themselves from DNA damage render them potentially more susceptible to oncogenesis, especially given their ability to self-renew and their long-term proliferative potential. We further review scientists' experience with gene-editing technologies to date, focusing on strategies to move these techniques toward implementation in safe and effective clinical trials.

CRISPR/Cas9-mediated gene editing in human zygotes using Cas9 protein.

PubMed

Tang, Lichun; Zeng, Yanting; Du, Hongzi; Gong, Mengmeng; Peng, Jin; Zhang, Buxi; Lei, Ming; Zhao, Fang; Wang, Weihua; Li, Xiaowei; Liu, Jianqiao

2017-06-01

Previous works using human tripronuclear zygotes suggested that the clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 system could be a tool in correcting disease-causing mutations. However, whether this system was applicable in normal human (dual pronuclear, 2PN) zygotes was unclear. Here we demonstrate that CRISPR/Cas9 is also effective as a gene-editing tool in human 2PN zygotes. By injection of Cas9 protein complexed with the appropriate sgRNAs and homology donors into one-cell human embryos, we demonstrated efficient homologous recombination-mediated correction of point mutations in HBB and G6PD. However, our results also reveal limitations of this correction procedure and highlight the need for further research.

IATA for skin sensitization potential – 1 out of 2 or 2 out of 3? ...

EPA Pesticide Factsheets

To meet EU regulatory requirements and to avoid or minimize animal testing, there is a need for non-animal methods to assess skin sensitization potential. Given the complexity of the skin sensitization endpoint, there is an expectation that integrated testing and assessment approaches (IATA) will need to be developed which rely on assays representing key events in the pathway. Three non-animal assays have been formally validated: the direct peptide reactivity assay (DPRA), the KeratinoSensTM assay and the h-CLAT assay. At the same time, there have been many efforts to develop IATA with the “2 out of 3” approach attracting much attention whereby a chemical is classified on the basis of the majority outcome. A set of 271 chemicals with mouse, human and non-animal sensitization test data was evaluated to compare the predictive performances of the 3 individual non-animal assays, their binary combinations and the ‘2 out of 3’ approach. The analysis revealed that the most predictive approach was to use both the DPRA and h-CLAT: 1. Perform DPRA – if positive, classify as a sensitizer; 2. If negative, perform h-CLAT – a positive outcome denotes a sensitizer, a negative, a non-sensitizer. With this approach, 83% (LLNA) and 93% (human) of the non-sensitizer predictions were correct, in contrast to the ‘2 out of 3’ approach which had 69% (LLNA) and 79% (human) of non-sensitizer predictions correct. The views expressed are those of the authors and do not ne

75 FR 47598 - Solicitation of Nomination for Appointment to the Advisory Committee on Minority Health; Correction

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-06

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Solicitation of Nomination for Appointment to the Advisory Committee on Minority Health; Correction AGENCY: Department of Health and Human Services, Office of the.... SUMMARY: The Department of Health and Human Services published a document in the Federal Register on...

Effects of transverse photon exchange in helium Rydberg states - Corrections beyond the Coulomb-Breit interaction

NASA Technical Reports Server (NTRS)

Au, C. K.

1989-01-01

The Breit correction only accounts for part of the transverse photon exchange correction in the calculation of the energy levels in helium Rydberg states. The remaining leading corrections are identified and each is expressed in an effective potential form. The relevance to the Casimir correction potential in various limits is also discussed.

Generation of Isogenic Human iPS Cell Line Precisely Corrected by Genome Editing Using the CRISPR/Cas9 System.

PubMed

Grobarczyk, Benjamin; Franco, Bénédicte; Hanon, Kevin; Malgrange, Brigitte

2015-10-01

Genome engineering and human iPS cells are two powerful technologies, which can be combined to highlight phenotypic differences and identify pathological mechanisms of complex diseases by providing isogenic cellular material. However, very few data are available regarding precise gene correction in human iPS cells. Here, we describe an optimized stepwise protocol to deliver CRISPR/Cas9 plasmids in human iPS cells. We highlight technical issues especially those associated to human stem cell culture and to the correction of a point mutation to obtain isogenic iPS cell line, without inserting any resistance cassette. Based on a two-steps clonal isolation protocol (mechanical picking followed by enzymatic dissociation), we succeed to select and expand corrected human iPS cell line with a great efficiency (more than 2% of the sequenced colonies). This protocol can also be used to obtain knock-out cell line from healthy iPS cell line by the NHEJ pathway (with about 15% efficiency) and reproduce disease phenotype. In addition, we also provide protocols for functional validation tests after every critical step.

Can currently available non-animal methods detect pre and pro-haptens relevant for skin sensitization?

PubMed

Patlewicz, Grace; Casati, Silvia; Basketter, David A; Asturiol, David; Roberts, David W; Lepoittevin, Jean-Pierre; Worth, Andrew P; Aschberger, Karin

2016-12-01

Predictive testing to characterize substances for their skin sensitization potential has historically been based on animal tests such as the Local Lymph Node Assay (LLNA). In recent years, regulations in the cosmetics and chemicals sectors have provided strong impetus to develop non-animal alternatives. Three test methods have undergone OECD validation: the direct peptide reactivity assay (DPRA), the KeratinoSens™ and the human Cell Line Activation Test (h-CLAT). Whilst these methods perform relatively well in predicting LLNA results, a concern raised is their ability to predict chemicals that need activation to be sensitizing (pre- or pro-haptens). This current study reviewed an EURL ECVAM dataset of 127 substances for which information was available in the LLNA and three non-animal test methods. Twenty eight of the sensitizers needed to be activated, with the majority being pre-haptens. These were correctly identified by 1 or more of the test methods. Six substances were categorized exclusively as pro-haptens, but were correctly identified by at least one of the cell-based assays. The analysis here showed that skin metabolism was not likely to be a major consideration for assessing sensitization potential and that sensitizers requiring activation could be identified correctly using one or more of the current non-animal methods. Published by Elsevier Inc.

Leading non-Gaussian corrections for diffusion orientation distribution function.

PubMed

Jensen, Jens H; Helpern, Joseph A; Tabesh, Ali

2014-02-01

An analytical representation of the leading non-Gaussian corrections for a class of diffusion orientation distribution functions (dODFs) is presented. This formula is constructed from the diffusion and diffusional kurtosis tensors, both of which may be estimated with diffusional kurtosis imaging (DKI). By incorporating model-independent non-Gaussian diffusion effects, it improves on the Gaussian approximation used in diffusion tensor imaging (DTI). This analytical representation therefore provides a natural foundation for DKI-based white matter fiber tractography, which has potential advantages over conventional DTI-based fiber tractography in generating more accurate predictions for the orientations of fiber bundles and in being able to directly resolve intra-voxel fiber crossings. The formula is illustrated with numerical simulations for a two-compartment model of fiber crossings and for human brain data. These results indicate that the inclusion of the leading non-Gaussian corrections can significantly affect fiber tractography in white matter regions, such as the centrum semiovale, where fiber crossings are common. 2013 John Wiley & Sons, Ltd.

Leading Non-Gaussian Corrections for Diffusion Orientation Distribution Function

PubMed Central

Jensen, Jens H.; Helpern, Joseph A.; Tabesh, Ali

2014-01-01

An analytical representation of the leading non-Gaussian corrections for a class of diffusion orientation distribution functions (dODFs) is presented. This formula is constructed out of the diffusion and diffusional kurtosis tensors, both of which may be estimated with diffusional kurtosis imaging (DKI). By incorporating model-independent non-Gaussian diffusion effects, it improves upon the Gaussian approximation used in diffusion tensor imaging (DTI). This analytical representation therefore provides a natural foundation for DKI-based white matter fiber tractography, which has potential advantages over conventional DTI-based fiber tractography in generating more accurate predictions for the orientations of fiber bundles and in being able to directly resolve intra-voxel fiber crossings. The formula is illustrated with numerical simulations for a two-compartment model of fiber crossings and for human brain data. These results indicate that the inclusion of the leading non-Gaussian corrections can significantly affect fiber tractography in white matter regions, such as the centrum semiovale, where fiber crossings are common. PMID:24738143

piggyBac transposons expressing full-length human dystrophin enable genetic correction of dystrophic mesoangioblasts

PubMed Central

Loperfido, Mariana; Jarmin, Susan; Dastidar, Sumitava; Di Matteo, Mario; Perini, Ilaria; Moore, Marc; Nair, Nisha; Samara-Kuko, Ermira; Athanasopoulos, Takis; Tedesco, Francesco Saverio; Dickson, George; Sampaolesi, Maurilio; VandenDriessche, Thierry; Chuah, Marinee K.

2016-01-01

Duchenne muscular dystrophy (DMD) is a genetic neuromuscular disorder caused by the absence of dystrophin. We developed a novel gene therapy approach based on the use of the piggyBac (PB) transposon system to deliver the coding DNA sequence (CDS) of either full-length human dystrophin (DYS: 11.1 kb) or truncated microdystrophins (MD1: 3.6 kb; MD2: 4 kb). PB transposons encoding microdystrophins were transfected in C2C12 myoblasts, yielding 65±2% MD1 and 66±2% MD2 expression in differentiated multinucleated myotubes. A hyperactive PB (hyPB) transposase was then deployed to enable transposition of the large-size PB transposon (17 kb) encoding the full-length DYS and green fluorescence protein (GFP). Stable GFP expression attaining 78±3% could be achieved in the C2C12 myoblasts that had undergone transposition. Western blot analysis demonstrated expression of the full-length human DYS protein in myotubes. Subsequently, dystrophic mesoangioblasts from a Golden Retriever muscular dystrophy dog were transfected with the large-size PB transposon resulting in 50±5% GFP-expressing cells after stable transposition. This was consistent with correction of the differentiated dystrophic mesoangioblasts following expression of full-length human DYS. These results pave the way toward a novel non-viral gene therapy approach for DMD using PB transposons underscoring their potential to deliver large therapeutic genes. PMID:26682797

Evaluation of attenuation and scatter correction requirements in small animal PET and SPECT imaging

NASA Astrophysics Data System (ADS)

Konik, Arda Bekir

Positron emission tomography (PET) and single photon emission tomography (SPECT) are two nuclear emission-imaging modalities that rely on the detection of high-energy photons emitted from radiotracers administered to the subject. The majority of these photons are attenuated (absorbed or scattered) in the body, resulting in count losses or deviations from true detection, which in turn degrades the accuracy of images. In clinical emission tomography, sophisticated correction methods are often required employing additional x-ray CT or radionuclide transmission scans. Having proven their potential in both clinical and research areas, both PET and SPECT are being adapted for small animal imaging. However, despite the growing interest in small animal emission tomography, little scientific information exists about the accuracy of these correction methods on smaller size objects, and what level of correction is required. The purpose of this work is to determine the role of attenuation and scatter corrections as a function of object size through simulations. The simulations were performed using Interactive Data Language (IDL) and a Monte Carlo based package, Geant4 application for emission tomography (GATE). In IDL simulations, PET and SPECT data acquisition were modeled in the presence of attenuation. A mathematical emission and attenuation phantom approximating a thorax slice and slices from real PET/CT data were scaled to 5 different sizes (i.e., human, dog, rabbit, rat and mouse). The simulated emission data collected from these objects were reconstructed. The reconstructed images, with and without attenuation correction, were compared to the ideal (i.e., non-attenuated) reconstruction. Next, using GATE, scatter fraction values (the ratio of the scatter counts to the total counts) of PET and SPECT scanners were measured for various sizes of NEMA (cylindrical phantoms representing small animals and human), MOBY (realistic mouse/rat model) and XCAT (realistic human model) digital phantoms. In addition, PET projection files for different sizes of MOBY phantoms were reconstructed in 6 different conditions including attenuation and scatter corrections. Selected regions were analyzed for these different reconstruction conditions and object sizes. Finally, real mouse data from the real version of the same small animal PET scanner we modeled in our simulations were analyzed for similar reconstruction conditions. Both our IDL and GATE simulations showed that, for small animal PET and SPECT, even the smallest size objects (˜2 cm diameter) showed ˜15% error when both attenuation and scatter were not corrected. However, a simple attenuation correction using a uniform attenuation map and object boundary obtained from emission data significantly reduces this error in non-lung regions (˜1% for smallest size and ˜6% for largest size). In lungs, emissions values were overestimated when only attenuation correction was performed. In addition, we did not observe any significant improvement between the uses of uniform or actual attenuation map (e.g., only ˜0.5% for largest size in PET studies). The scatter correction was not significant for smaller size objects, but became increasingly important for larger sizes objects. These results suggest that for all mouse sizes and most rat sizes, uniform attenuation correction can be performed using emission data only. For smaller sizes up to ˜ 4 cm, scatter correction is not required even in lung regions. For larger sizes if accurate quantization needed, additional transmission scan may be required to estimate an accurate attenuation map for both attenuation and scatter corrections.

Placental transporter localization and expression in the Human: the importance of species, sex, and gestational age differences†

PubMed Central

Walker, Natasha; Filis, Panagiotis; Soffientini, Ugo; Bellingham, Michelle; O’Shaughnessy, Peter J; Fowler, Paul A

2017-01-01

Abstract The placenta is a critical organ during pregnancy, essential for the provision of an optimal intrauterine environment, with fetal survival, growth, and development relying on correct placental function. It must allow nutritional compounds and relevant hormones to pass into the fetal bloodstream and metabolic waste products to be cleared. It also acts as a semipermeable barrier to potentially harmful chemicals, both endogenous and exogenous. Transporter proteins allow for bidirectional transport and are found in the syncytiotrophoblast of the placenta and endothelium of fetal capillaries. The major transporter families in the human placenta are ATP-binding cassette (ABC) and solute carrier (SLC), and insufficiency of these transporters may lead to deleterious effects on the fetus. Transporter expression levels are gestation-dependent and this is of considerable clinical interest as levels of drug resistance may be altered from one trimester to the next. This highlights the importance of these transporters in mediating correct and timely transplacental passage of essential compounds but also for efflux of potentially toxic drugs and xenobiotics. We review the current literature on placental molecular transporters with respect to their localization and ontogeny, the influence of fetal sex, and the relevance of animal models. We conclude that a paucity of information exists, and further studies are required to unlock the enigma of this dynamic organ. PMID:28339967

Quantification of regenerative potential in primary human mammary epithelial cells

PubMed Central

Linnemann, Jelena R.; Miura, Haruko; Meixner, Lisa K.; Irmler, Martin; Kloos, Uwe J.; Hirschi, Benjamin; Bartsch, Harald S.; Sass, Steffen; Beckers, Johannes; Theis, Fabian J.; Gabka, Christian; Sotlar, Karl; Scheel, Christina H.

2015-01-01

We present an organoid regeneration assay in which freshly isolated human mammary epithelial cells are cultured in adherent or floating collagen gels, corresponding to a rigid or compliant matrix environment. In both conditions, luminal progenitors form spheres, whereas basal cells generate branched ductal structures. In compliant but not rigid collagen gels, branching ducts form alveoli at their tips, express basal and luminal markers at correct positions, and display contractility, which is required for alveologenesis. Thereby, branched structures generated in compliant collagen gels resemble terminal ductal-lobular units (TDLUs), the functional units of the mammary gland. Using the membrane metallo-endopeptidase CD10 as a surface marker enriches for TDLU formation and reveals the presence of stromal cells within the CD49fhi/EpCAM− population. In summary, we describe a defined in vitro assay system to quantify cells with regenerative potential and systematically investigate their interaction with the physical environment at distinct steps of morphogenesis. PMID:26071498

78 FR 25470 - Notice of Inventory Completion for Native American Human Remains and Associated Funerary Objects...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-01

....R50000] Notice of Inventory Completion for Native American Human Remains and Associated Funerary Objects... corrected an inventory of human remains and associated funerary objects, published in a Notice of Inventory... associated funerary objects from the Bynum Mounds site. Transfer of control of the items in this correction...

Influence of Misalignment on High-Order Aberration Correction for Normal Human Eyes

NASA Astrophysics Data System (ADS)

Zhao, Hao-Xin; Xu, Bing; Xue, Li-Xia; Dai, Yun; Liu, Qian; Rao, Xue-Jun

2008-04-01

Although a compensation device can correct aberrations of human eyes, the effect will be degraded by its misalignment, especially for high-order aberration correction. We calculate the positioning tolerance of correction device for high-order aberrations, and within what degree the correcting effect is better than low-order aberration (defocus and astigmatism) correction. With fixed certain misalignment within the positioning tolerance, we calculate the residual wavefront rms aberration of the first-6 to first-35 terms along with the 3rd-5th terms of aberrations corrected, and the combined first-13 terms of aberrations are also studied under the same quantity of misalignment. However, the correction effect of high-order aberrations does not meliorate along with the increase of the high-order terms under some misalignment, moreover, some simple combined terms correction can achieve similar result as complex combinations. These results suggest that it is unnecessary to correct too much the terms of high-order aberrations which are difficult to accomplish in practice, and gives confidence to correct high-order aberrations out of the laboratory.

Dysregulation of lysosomal morphology by pathogenic LRRK2 is corrected by TPC2 inhibition.

PubMed

Hockey, Leanne N; Kilpatrick, Bethan S; Eden, Emily R; Lin-Moshier, Yaping; Brailoiu, G Cristina; Brailoiu, Eugen; Futter, Clare E; Schapira, Anthony H; Marchant, Jonathan S; Patel, Sandip

2015-01-15

Two-pore channels (TPCs) are endolysosomal ion channels implicated in Ca(2+) signalling from acidic organelles. The relevance of these ubiquitous proteins for human disease, however, is unclear. Here, we report that lysosomes are enlarged and aggregated in fibroblasts from Parkinson disease patients with the common G2019S mutation in LRRK2. Defects were corrected by molecular silencing of TPC2, pharmacological inhibition of TPC regulators [Rab7, NAADP and PtdIns(3,5)P2] and buffering local Ca(2+) increases. NAADP-evoked Ca(2+) signals were exaggerated in diseased cells. TPC2 is thus a potential drug target within a pathogenic LRRK2 cascade that disrupts Ca(2+)-dependent trafficking in Parkinson disease. © 2015. Published by The Company of Biologists Ltd.

Development of a practical image-based scatter correction method for brain perfusion SPECT: comparison with the TEW method.

PubMed

Shidahara, Miho; Watabe, Hiroshi; Kim, Kyeong Min; Kato, Takashi; Kawatsu, Shoji; Kato, Rikio; Yoshimura, Kumiko; Iida, Hidehiro; Ito, Kengo

2005-10-01

An image-based scatter correction (IBSC) method was developed to convert scatter-uncorrected into scatter-corrected SPECT images. The purpose of this study was to validate this method by means of phantom simulations and human studies with 99mTc-labeled tracers, based on comparison with the conventional triple energy window (TEW) method. The IBSC method corrects scatter on the reconstructed image I(mub)AC with Chang's attenuation correction factor. The scatter component image is estimated by convolving I(mub)AC with a scatter function followed by multiplication with an image-based scatter fraction function. The IBSC method was evaluated with Monte Carlo simulations and 99mTc-ethyl cysteinate dimer SPECT human brain perfusion studies obtained from five volunteers. The image counts and contrast of the scatter-corrected images obtained by the IBSC and TEW methods were compared. Using data obtained from the simulations, the image counts and contrast of the scatter-corrected images obtained by the IBSC and TEW methods were found to be nearly identical for both gray and white matter. In human brain images, no significant differences in image contrast were observed between the IBSC and TEW methods. The IBSC method is a simple scatter correction technique feasible for use in clinical routine.

Final corrective action study for the former CCC/USDA facility in Ramona, Kansas.

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

LaFreniere, L. M.

Past operations at a grain storage facility formerly leased and operated by the Commodity Credit Corporation of the U.S. Department of Agriculture (CCC/USDA) in Ramona, Kansas, resulted in low concentrations of carbon tetrachloride in groundwater that slightly exceed the regulatory standard in only one location. As requested by the Kansas Department of Health and Environment, the CCC/USDA has prepared a Corrective Action Study (CAS) for the facility. The CAS examines corrective actions to address groundwater impacted by the former CCC/USDA facility but not releases caused by other potential groundwater contamination sources in Ramona. Four remedial alternatives were considered in themore » CAS. The recommended remedial alternative in the CAS consists of Environmental Use Control to prevent the inadvertent use of groundwater as a water supply source, coupled with groundwater monitoring to verify the continued natural improvement in groundwater quality. The Commodity Credit Corporation of the U.S. Department of Agriculture (CCC/USDA) has directed Argonne National Laboratory to prepare a Corrective Action Study (CAS), consistent with guidance from the Kansas Department of Health and Environment (KDHE 2001a), for the CCC/USDA grain storage facility formerly located in Ramona, Kansas. This effort is pursuant to a KDHE (2007a) request. Although carbon tetrachloride levels at the Ramona site are low, they remain above the Kansas Tier 2 risk-based screening level (RBSL) and the U.S. Environmental Protection Agency (EPA) maximum contaminant level (MCL) of 5 {micro}g/L (Kansas 2003, 2004). In its request for the CAS, the KDHE (2007a) stated that, because of these levels, risk is associated with potential future exposure to contaminated groundwater. The KDHE therefore determined that additional measures are warranted to limit future use of the property and/or exposure to contaminated media as part of site closure. The KDHE further requested comparison of at least two corrective action alternatives to the 'no-action' alternative, as the basis for the Draft Corrective Action Decision for the site. The history and nature of the contamination and previous investigations are summarized in Section 2. Also included in Section 2 is an evaluation of human and environmental targets and potential exposure pathways. Section 3 describes the corrective action goals and applicable or relevant and appropriate requirements (ARARs). Section 4 describes four alternatives, Section 5 analyzes the alternatives in detail, and Section 6 compares the alternatives. Section 6 also includes a summary and a recommended corrective action.« less

Gold internal standard correction for elemental imaging of soft tissue sections by LA-ICP-MS: element distribution in eye microstructures.

PubMed

Konz, Ioana; Fernández, Beatriz; Fernández, M Luisa; Pereiro, Rosario; González, Héctor; Alvarez, Lydia; Coca-Prados, Miguel; Sanz-Medel, Alfredo

2013-04-01

Laser ablation coupled to inductively coupled plasma mass spectrometry has been developed for the elemental imaging of Mg, Fe and Cu distribution in histological tissue sections of fixed eyes, embedded in paraffin, from human donors (cadavers). This work presents the development of a novel internal standard correction methodology based on the deposition of a homogeneous thin gold film on the tissue surface and the use of the (197)Au(+) signal as internal standard. Sample preparation (tissue section thickness) and laser conditions were carefully optimized, and internal normalisation using (197)Au(+) was compared with (13)C(+) correction for imaging applications. (24)Mg(+), (56)Fe(+) and (63)Cu(+) distributions were investigated in histological sections of the anterior segment of the eye (including the iris, ciliary body, cornea and trabecular meshwork) and were shown to be heterogeneously distributed along those tissue structures. Reproducibility was assessed by imaging different human eye sections from the same donor and from ten different eyes from adult normal donors, which showed that similar spatial maps were obtained and therefore demonstrate the analytical potential of using (197)Au(+) as internal standard. The proposed analytical approach could offer a robust tool with great practical interest for clinical studies, e.g. to investigate trace element distribution of metals and their alterations in ocular diseases.

Rapid detection and subtyping of human influenza A viruses and reassortants by pyrosequencing.

PubMed

Deng, Yi-Mo; Caldwell, Natalie; Barr, Ian G

2011-01-01

Given the continuing co-circulation of the 2009 H1N1 pandemic influenza A viruses with seasonal H3N2 viruses, rapid and reliable detection of newly emerging influenza reassortant viruses is important to enhance our influenza surveillance. A novel pyrosequencing assay was developed for the rapid identification and subtyping of potential human influenza A virus reassortants based on all eight gene segments of the virus. Except for HA and NA genes, one universal set of primers was used to amplify and subtype each of the six internal genes. With this method, all eight gene segments of 57 laboratory isolates and 17 original specimens of seasonal H1N1, H3N2 and 2009 H1N1 pandemic viruses were correctly matched with their corresponding subtypes. In addition, this method was shown to be capable of detecting reassortant viruses by correctly identifying the source of all 8 gene segments from three vaccine production reassortant viruses and three H1N2 viruses. In summary, this pyrosequencing assay is a sensitive and specific procedure for screening large numbers of viruses for reassortment events amongst the commonly circulating human influenza A viruses, which is more rapid and cheaper than using conventional sequencing approaches.

Rapid Detection and Subtyping of Human Influenza A Viruses and Reassortants by Pyrosequencing

PubMed Central

Deng, Yi-Mo; Caldwell, Natalie; Barr, Ian G.

2011-01-01

Background Given the continuing co-circulation of the 2009 H1N1 pandemic influenza A viruses with seasonal H3N2 viruses, rapid and reliable detection of newly emerging influenza reassortant viruses is important to enhance our influenza surveillance. Methodology/Principal Findings A novel pyrosequencing assay was developed for the rapid identification and subtyping of potential human influenza A virus reassortants based on all eight gene segments of the virus. Except for HA and NA genes, one universal set of primers was used to amplify and subtype each of the six internal genes. With this method, all eight gene segments of 57 laboratory isolates and 17 original specimens of seasonal H1N1, H3N2 and 2009 H1N1 pandemic viruses were correctly matched with their corresponding subtypes. In addition, this method was shown to be capable of detecting reassortant viruses by correctly identifying the source of all 8 gene segments from three vaccine production reassortant viruses and three H1N2 viruses. Conclusions/Significance In summary, this pyrosequencing assay is a sensitive and specific procedure for screening large numbers of viruses for reassortment events amongst the commonly circulating human influenza A viruses, which is more rapid and cheaper than using conventional sequencing approaches. PMID:21886790

Turboprop IDEAL: a motion-resistant fat-water separation technique.

PubMed

Huo, Donglai; Li, Zhiqiang; Aboussouan, Eric; Karis, John P; Pipe, James G

2009-01-01

Suppression of the fat signal in MRI is very important for many clinical applications. Multi-point water-fat separation methods, such as IDEAL (Iterative Decomposition of water and fat with Echo Asymmetry and Least-squares estimation), can robustly separate water and fat signal, but inevitably increase scan time, making separated images more easily affected by patient motions. PROPELLER (Periodically Rotated Overlapping ParallEL Lines with Enhanced Reconstruction) and Turboprop techniques offer an effective approach to correct for motion artifacts. By combining these techniques together, we demonstrate that the new TP-IDEAL method can provide reliable water-fat separation with robust motion correction. The Turboprop sequence was modified to acquire source images, and motion correction algorithms were adjusted to assure the registration between different echo images. Theoretical calculations were performed to predict the optimal shift and spacing of the gradient echoes. Phantom images were acquired, and results were compared with regular FSE-IDEAL. Both T1- and T2-weighted images of the human brain were used to demonstrate the effectiveness of motion correction. TP-IDEAL images were also acquired for pelvis, knee, and foot, showing great potential of this technique for general clinical applications.

Potentiator Ivacaftor Abrogates Pharmacological Correction of ΔF508 CFTR in Cystic Fibrosis

PubMed Central

Cholon, Deborah M.; Quinney, Nancy L.; Fulcher, M. Leslie; Esther, Charles R.; Das, Jhuma; Dokholyan, Nikolay V.; Randell, Scott H.; Boucher, Richard C.; Gentzsch, Martina

2014-01-01

Cystic Fibrosis (CF) is caused by mutations in the CF transmembrane conductance regulator (CFTR). Newly developed “correctors” such as lumacaftor (VX-809) that improve CFTR maturation and trafficking and “potentiators” such as ivacaftor (VX-770) that enhance channel activity may provide important advances in CF therapy. Although VX-770 has demonstrated substantial clinical efficacy in the small subset of patients with a mutation (G551D) that affects only channel activity, a single compound is not sufficient to treat patients with the more common CFTR mutation, ΔF508. Thus, patients with ΔF508 will likely require treatment with both correctors and potentiators to achieve clinical benefit. However, whereas the effectiveness of acute treatment with this drug combination has been demonstrated in vitro, the impact of chronic therapy has not been established. In studies of human primary airway epithelial cells, we found that both acute and chronic treatment with VX-770 improved CFTR function in cells with the G551D mutation, consistent with clinical studies. In contrast, chronic VX-770 administration caused a dose-dependent reversal of VX-809-mediated CFTR correction in ΔF508 homozygous cultures. This result reflected the destabilization of corrected ΔF508 CFTR by VX-770, dramatically increasing its turnover rate. Chronic VX-770 treatment also reduced mature wild-type CFTR levels and function. These findings demonstrate that chronic treatment with CFTR potentiators and correctors may have unexpected effects that cannot be predicted from short-term studies. Combining of these drugs to maximize rescue of ΔF508 CFTR may require changes in dosing and/or development of new potentiator compounds that do not interfere with CFTR stability. PMID:25101886

A decision support system and rule-based algorithm to augment the human interpretation of the 12-lead electrocardiogram.

PubMed

Cairns, Andrew W; Bond, Raymond R; Finlay, Dewar D; Guldenring, Daniel; Badilini, Fabio; Libretti, Guido; Peace, Aaron J; Leslie, Stephen J

The 12-lead Electrocardiogram (ECG) has been used to detect cardiac abnormalities in the same format for more than 70years. However, due to the complex nature of 12-lead ECG interpretation, there is a significant cognitive workload required from the interpreter. This complexity in ECG interpretation often leads to errors in diagnosis and subsequent treatment. We have previously reported on the development of an ECG interpretation support system designed to augment the human interpretation process. This computerised decision support system has been named 'Interactive Progressive based Interpretation' (IPI). In this study, a decision support algorithm was built into the IPI system to suggest potential diagnoses based on the interpreter's annotations of the 12-lead ECG. We hypothesise semi-automatic interpretation using a digital assistant can be an optimal man-machine model for ECG interpretation. To improve interpretation accuracy and reduce missed co-abnormalities. The Differential Diagnoses Algorithm (DDA) was developed using web technologies where diagnostic ECG criteria are defined in an open storage format, Javascript Object Notation (JSON), which is queried using a rule-based reasoning algorithm to suggest diagnoses. To test our hypothesis, a counterbalanced trial was designed where subjects interpreted ECGs using the conventional approach and using the IPI+DDA approach. A total of 375 interpretations were collected. The IPI+DDA approach was shown to improve diagnostic accuracy by 8.7% (although not statistically significant, p-value=0.1852), the IPI+DDA suggested the correct interpretation more often than the human interpreter in 7/10 cases (varying statistical significance). Human interpretation accuracy increased to 70% when seven suggestions were generated. Although results were not found to be statistically significant, we found; 1) our decision support tool increased the number of correct interpretations, 2) the DDA algorithm suggested the correct interpretation more often than humans, and 3) as many as 7 computerised diagnostic suggestions augmented human decision making in ECG interpretation. Statistical significance may be achieved by expanding sample size. Copyright © 2017 Elsevier Inc. All rights reserved.

Production of Gene-Corrected Adult Beta Globin Protein in Human Erythrocytes Differentiated from Patient iPSCs After Genome Editing of the Sickle Point Mutation.

PubMed

Huang, Xiaosong; Wang, Ying; Yan, Wei; Smith, Cory; Ye, Zhaohui; Wang, Jing; Gao, Yongxing; Mendelsohn, Laurel; Cheng, Linzhao

2015-05-01

Human induced pluripotent stem cells (iPSCs) and genome editing provide a precise way to generate gene-corrected cells for disease modeling and cell therapies. Human iPSCs generated from sickle cell disease (SCD) patients have a homozygous missense point mutation in the HBB gene encoding adult β-globin proteins, and are used as a model system to improve strategies of human gene therapy. We demonstrate that the CRISPR/Cas9 system designer nuclease is much more efficient in stimulating gene targeting of the endogenous HBB locus near the SCD point mutation in human iPSCs than zinc finger nucleases and TALENs. Using a specific guide RNA and Cas9, we readily corrected one allele of the SCD HBB gene in human iPSCs by homologous recombination with a donor DNA template containing the wild-type HBB DNA and a selection cassette that was subsequently removed to avoid possible interference of HBB transcription and translation. We chose targeted iPSC clones that have one corrected and one disrupted SCD allele for erythroid differentiation assays, using an improved xeno-free and feeder-free culture condition we recently established. Erythrocytes from either the corrected or its parental (uncorrected) iPSC line were generated with similar efficiencies. Currently ∼6%-10% of these differentiated erythrocytes indeed lacked nuclei, characteristic of further matured erythrocytes called reticulocytes. We also detected the 16-kDa β-globin protein expressed from the corrected HBB allele in the erythrocytes differentiated from genome-edited iPSCs. Our results represent a significant step toward the clinical applications of genome editing using patient-derived iPSCs to generate disease-free cells for cell and gene therapies. Stem Cells 2015;33:1470-1479. © 2015 AlphaMed Press.

Characterizing and Modulating Brain Circuitry through Transcranial Magnetic Stimulation Combined with Electroencephalography.

PubMed

Farzan, Faranak; Vernet, Marine; Shafi, Mouhsin M D; Rotenberg, Alexander; Daskalakis, Zafiris J; Pascual-Leone, Alvaro

2016-01-01

The concurrent combination of transcranial magnetic stimulation (TMS) with electroencephalography (TMS-EEG) is a powerful technology for characterizing and modulating brain networks across developmental, behavioral, and disease states. Given the global initiatives in mapping the human brain, recognition of the utility of this technique is growing across neuroscience disciplines. Importantly, TMS-EEG offers translational biomarkers that can be applied in health and disease, across the lifespan, and in humans and animals, bridging the gap between animal models and human studies. However, to utilize the full potential of TMS-EEG methodology, standardization of TMS-EEG study protocols is needed. In this article, we review the principles of TMS-EEG methodology, factors impacting TMS-EEG outcome measures, and the techniques for preventing and correcting artifacts in TMS-EEG data. To promote the standardization of this technique, we provide comprehensive guides for designing TMS-EEG studies and conducting TMS-EEG experiments. We conclude by reviewing the application of TMS-EEG in basic, cognitive and clinical neurosciences, and evaluate the potential of this emerging technology in brain research.

Characterizing and Modulating Brain Circuitry through Transcranial Magnetic Stimulation Combined with Electroencephalography

PubMed Central

Farzan, Faranak; Vernet, Marine; Shafi, Mouhsin M. D.; Rotenberg, Alexander; Daskalakis, Zafiris J.; Pascual-Leone, Alvaro

2016-01-01

The concurrent combination of transcranial magnetic stimulation (TMS) with electroencephalography (TMS-EEG) is a powerful technology for characterizing and modulating brain networks across developmental, behavioral, and disease states. Given the global initiatives in mapping the human brain, recognition of the utility of this technique is growing across neuroscience disciplines. Importantly, TMS-EEG offers translational biomarkers that can be applied in health and disease, across the lifespan, and in humans and animals, bridging the gap between animal models and human studies. However, to utilize the full potential of TMS-EEG methodology, standardization of TMS-EEG study protocols is needed. In this article, we review the principles of TMS-EEG methodology, factors impacting TMS-EEG outcome measures, and the techniques for preventing and correcting artifacts in TMS-EEG data. To promote the standardization of this technique, we provide comprehensive guides for designing TMS-EEG studies and conducting TMS-EEG experiments. We conclude by reviewing the application of TMS-EEG in basic, cognitive and clinical neurosciences, and evaluate the potential of this emerging technology in brain research. PMID:27713691

Does Human Milk Modulate Body Composition in Late Preterm Infants at Term-Corrected Age?

PubMed

Giannì, Maria Lorella; Consonni, Dario; Liotto, Nadia; Roggero, Paola; Morlacchi, Laura; Piemontese, Pasqua; Menis, Camilla; Mosca, Fabio

2016-10-23

(1) Background: Late preterm infants account for the majority of preterm births and are at risk of altered body composition. Because body composition modulates later health outcomes and human milk is recommended as the normal method for infant feeding, we sought to investigate whether human milk feeding in early life can modulate body composition development in late preterm infants; (2) Methods: Neonatal, anthropometric and feeding data of 284 late preterm infants were collected. Body composition was evaluated at term-corrected age by air displacement plethysmography. The effect of human milk feeding on fat-free mass and fat mass content was evaluated using multiple linear regression analysis; (3) Results: Human milk was fed to 68% of the infants. According to multiple regression analysis, being fed any human milk at discharge and at  term-corrected and being fed exclusively human milk at term-corrected age were positively associated with fat-free mass content(β = -47.9, 95% confidence interval (CI) = -95.7; -0.18; p = 0.049; β = -89.6, 95% CI = -131.5; -47.7; p < 0.0001; β = -104.1, 95% CI = -151.4; -56.7, p < 0.0001); (4) Conclusion: Human milk feeding appears to be associated with fat-free mass deposition in late preterm infants. Healthcare professionals should direct efforts toward promoting and supporting breastfeeding in these vulnerable infants.

Detection and identification of human targets in radar data

NASA Astrophysics Data System (ADS)

Gürbüz, Sevgi Z.; Melvin, William L.; Williams, Douglas B.

2007-04-01

Radar offers unique advantages over other sensors, such as visual or seismic sensors, for human target detection. Many situations, especially military applications, prevent the placement of video cameras or implantment seismic sensors in the area being observed, because of security or other threats. However, radar can operate far away from potential targets, and functions during daytime as well as nighttime, in virtually all weather conditions. In this paper, we examine the problem of human target detection and identification using single-channel, airborne, synthetic aperture radar (SAR). Human targets are differentiated from other detected slow-moving targets by analyzing the spectrogram of each potential target. Human spectrograms are unique, and can be used not just to identify targets as human, but also to determine features about the human target being observed, such as size, gender, action, and speed. A 12-point human model, together with kinematic equations of motion for each body part, is used to calculate the expected target return and spectrogram. A MATLAB simulation environment is developed including ground clutter, human and non-human targets for the testing of spectrogram-based detection and identification algorithms. Simulations show that spectrograms have some ability to detect and identify human targets in low noise. An example gender discrimination system correctly detected 83.97% of males and 91.11% of females. The problems and limitations of spectrogram-based methods in high clutter environments are discussed. The SNR loss inherent to spectrogram-based methods is quantified. An alternate detection and identification method that will be used as a basis for future work is proposed.

Humanizing Prisons with Animals: A Closer Look at "Cell Dogs" and Horse Programs in Correctional Institutions

ERIC Educational Resources Information Center

Deaton, Christiane

2005-01-01

If correctional education aims to transform individuals and bring about change, we need to consider the whole person who comes with human needs, emotions and attitudes. In order to expand our approach, alternative programs should be explored. A somewhat unusual but very promising approach to address offenders' human needs is the use of animals in …

Empirical Derivation of Correction Factors for Human Spiral Ganglion Cell Nucleus and Nucleolus Count Units.

PubMed

Robert, Mark E; Linthicum, Fred H

2016-01-01

Profile count method for estimating cell number in sectioned tissue applies a correction factor for double count (resulting from transection during sectioning) of count units selected to represent the cell. For human spiral ganglion cell counts, we attempted to address apparent confusion between published correction factors for nucleus and nucleolus count units that are identical despite the role of count unit diameter in a commonly used correction factor formula. We examined a portion of human cochlea to empirically derive correction factors for the 2 count units, using 3-dimensional reconstruction software to identify double counts. The Neurotology and House Histological Temporal Bone Laboratory at University of California at Los Angeles. Using a fully sectioned and stained human temporal bone, we identified and generated digital images of sections of the modiolar region of the lower first turn of cochlea, identified count units with a light microscope, labeled them on corresponding digital sections, and used 3-dimensional reconstruction software to identify double-counted count units. For 25 consecutive sections, we determined that double-count correction factors for nucleus count unit (0.91) and nucleolus count unit (0.92) matched the published factors. We discovered that nuclei and, therefore, spiral ganglion cells were undercounted by 6.3% when using nucleolus count units. We determined that correction factors for count units must include an element for undercounting spiral ganglion cells as well as the double-count element. We recommend a correction factor of 0.91 for the nucleus count unit and 0.98 for the nucleolus count unit when using 20-µm sections. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2015.

76 FR 79198 - Generic Drug User Fee; Public Meeting; Correction

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-21

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0381] Generic Drug User Fee; Public Meeting; Correction AGENCY: Food and Drug Administration, HHS. ACTION: Notice; correction. SUMMARY: The Food and Drug Administration (FDA) is correcting a notice that appeared...

Testing chemical carcinogenicity by using a transcriptomics HepaRG-based model?

PubMed Central

Doktorova, T. Y.; Yildirimman, Reha; Ceelen, Liesbeth; Vilardell, Mireia; Vanhaecke, Tamara; Vinken, Mathieu; Ates, Gamze; Heymans, Anja; Gmuender, Hans; Bort, Roque; Corvi, Raffaella; Phrakonkham, Pascal; Li, Ruoya; Mouchet, Nicolas; Chesne, Christophe; van Delft, Joost; Kleinjans, Jos; Castell, Jose; Herwig, Ralf; Rogiers, Vera

2014-01-01

The EU FP6 project carcinoGENOMICS explored the combination of toxicogenomics and in vitro cell culture models for identifying organotypical genotoxic- and non-genotoxic carcinogen-specific gene signatures. Here the performance of its gene classifier, derived from exposure of metabolically competent human HepaRG cells to prototypical non-carcinogens (10 compounds) and hepatocarcinogens (20 compounds), is reported. Analysis of the data at the gene and the pathway level by using independent biostatistical approaches showed a distinct separation of genotoxic from non-genotoxic hepatocarcinogens and non-carcinogens (up to 88 % correct prediction). The most characteristic pathway responding to genotoxic exposure was DNA damage. Interlaboratory reproducibility was assessed by blindly testing of three compounds, from the set of 30 compounds, by three independent laboratories. Subsequent classification of these compounds resulted in correct prediction of the genotoxicants. As expected, results on the non-genotoxic carcinogens and the non-carcinogens were less predictive. In conclusion, the combination of transcriptomics with the HepaRG in vitro cell model provides a potential weight of evidence approach for the evaluation of the genotoxic potential of chemical substances. PMID:26417288

HLA-E–restricted regulatory CD8+ T cells are involved in development and control of human autoimmune type 1 diabetes

PubMed Central

Jiang, Hong; Canfield, Steve M.; Gallagher, Mary P.; Jiang, Hong H.; Jiang, Yihua; Zheng, Zongyu; Chess, Leonard

2010-01-01

A key feature of the immune system is its ability to discriminate self from nonself. Breakdown in any of the mechanisms that maintain unresponsiveness to self (a state known as self-tolerance) contributes to the development of autoimmune conditions. Recent studies in mice show that CD8+ T cells specific for the unconventional MHC class I molecule Qa-1 bound to peptides derived from the signal sequence of Hsp60 (Hsp60sp) contribute to self/nonself discrimination. However, it is unclear whether they exist in humans and play a role in human autoimmune diseases. Here we have shown that CD8+ T cells specific for Hsp60sp bound to HLA-E (the human homolog of Qa-1) exist and play an important role in maintaining peripheral self-tolerance by discriminating self from nonself in humans. Furthermore, in the majority of type 1 diabetes (T1D) patients tested, there was a specific defect in CD8+ T cell recognition of HLA-E/Hsp60sp, which was associated with failure of self/nonself discrimination. However, the defect in the CD8+ T cells from most of the T1D patients tested could be corrected in vitro by exposure to autologous immature DCs loaded with the Hsp60sp peptide. These data suggest that HLA-E–restricted CD8+ T cells may play an important role in keeping self-reactive T cells in check. Thus, correction of this defect could be a potentially effective and safe approach in the therapy of T1D. PMID:20877010

Correction of the Middle Eastern M712T mutation causing GNE myopathy by trans-splicing.

PubMed

Tal-Goldberg, Tzukit; Lorain, Stéphanie; Mitrani-Rosenbaum, Stella

2014-06-01

GNE myopathy is a rare neuromuscular autosomal recessive disease, resulting from mutations in the gene UDP N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE). The most frequent mutation is the single homozygous missense mutation, M712T-the Middle Eastern mutation-located ten amino acids before the end of the protein. We have used an adeno-associated virus (AAV)-based trans-splicing (TS) vector as a gene therapy tool to overcome this mutation by replacing the mutated last exon of GNE by the wild-type exon while preserving the natural endogenous regulatory machinery. We have designed relevant plasmids directed either to mouse or to human GNE. Following transfection of C2C12 murine muscle cells with the mouse TS vectors, we have been able to detect by nested RT-PCR trans-spliced molecules carrying the wild-type exon 12 of GNE. Similarly, transfection of HEK293 human cells with the human-directed TS vectors resulted in the generation of trans-spliced human GNE RNA molecules. Furthermore, infection of primary muscle cells from a GNE myopathy patient carrying the homozygous M712T mutation, with an AAV8-based viral vector carrying a human-directed TS construct, resulted in the generation of wild-type GNE transcripts in addition to the mutated ones. These studies provide a proof of concept that the TS approach could be used to partially correct the Middle Eastern mutation in GNE myopathy patients. These results provide the basis for in vivo research in animal models using the AAV platform with TS plasmids as a potential genetic therapy for GNE myopathy.

Research on the liquid crystal adaptive optics system for human retinal imaging

NASA Astrophysics Data System (ADS)

Zhang, Lei; Tong, Shoufeng; Song, Yansong; Zhao, Xin

2013-12-01

The blood vessels only in Human eye retinal can be observed directly. Many diseases that are not obvious in their early symptom can be diagnosed through observing the changes of distal micro blood vessel. In order to obtain the high resolution human retinal images,an adaptive optical system for correcting the aberration of the human eye was designed by using the Shack-Hartmann wavefront sensor and the Liquid Crystal Spatial Light Modulator(LCLSM) .For a subject eye with 8m-1 (8D)myopia, the wavefront error is reduced to 0.084 λ PV and 0.12 λRMS after adaptive optics(AO) correction ,which has reached diffraction limit.The results show that the LCLSM based AO system has the ability of correcting the aberration of the human eye efficiently,and making the blurred photoreceptor cell to clearly image on a CCD camera.

Continuous Glucose Monitoring in Subjects with Type 1 Diabetes: Improvement in Accuracy by Correcting for Background Current

PubMed Central

Youssef, Joseph El; Engle, Julia M.; Massoud, Ryan G.; Ward, W. Kenneth

2010-01-01

Abstract Background A cause of suboptimal accuracy in amperometric glucose sensors is the presence of a background current (current produced in the absence of glucose) that is not accounted for. We hypothesized that a mathematical correction for the estimated background current of a commercially available sensor would lead to greater accuracy compared to a situation in which we assumed the background current to be zero. We also tested whether increasing the frequency of sensor calibration would improve sensor accuracy. Methods This report includes analysis of 20 sensor datasets from seven human subjects with type 1 diabetes. Data were divided into a training set for algorithm development and a validation set on which the algorithm was tested. A range of potential background currents was tested. Results Use of the background current correction of 4 nA led to a substantial improvement in accuracy (improvement of absolute relative difference or absolute difference of 3.5–5.5 units). An increase in calibration frequency led to a modest accuracy improvement, with an optimum at every 4 h. Conclusions Compared to no correction, a correction for the estimated background current of a commercially available glucose sensor led to greater accuracy and better detection of hypoglycemia and hyperglycemia. The accuracy-optimizing scheme presented here can be implemented in real time. PMID:20879968

The potential of pigeons as surrogate observers in medical image perception studies

NASA Astrophysics Data System (ADS)

Krupinski, Elizabeth A.; Levenson, Richard M.; Navarro, Victor; Wasserman, Edward A.

2016-03-01

Assessment of medical image quality and how changes in image appearance impact performance are critical but assessment can be expensive and time-consuming. Could an animal (pigeon) observer with well-known visual skills and documented ability to distinguish complex visual stimuli serve as a surrogate for the human observer? Using sets of whole slide pathology (WSI) and mammographic images we trained pigeons (cohorts of 4) to detect and/or classify lesions in medical images. Standard training methods were used. A chamber equipped with a 15' display with a resistive touchscreen was used to display the images and record responses (pecks). Pigeon pellets were dispensed for correct responses. The pigeons readily learned to distinguish benign from malignant breast cancer histopathology in WSI (mean % correct responses rose 50% to 85% over 15 days) and generalized readily from 4X to 10X and 20X magnifications; to detect microcalcifications (mean % correct responses rose 50% to over 85% over 25 days); to distinguish benign from malignant breast masses (3 of 4 birds learned this task to around 80% and 60% over 10 days); and ignore compression artifacts in WSI (performance with uncompressed slides averaged 95% correct; 15:1 and 27:1 compression slides averaged 92% and 90% correct). Pigeons models may help us better understand medical image perception and may be useful in quality assessment by serving as surrogate observers for certain types of studies.

A Prospective Treatment Option for Lysosomal Storage Diseases: CRISPR/Cas9 Gene Editing Technology for Mutation Correction in Induced Pluripotent Stem Cells.

PubMed

Christensen, Chloe L; Choy, Francis Y M

2017-02-24

Ease of design, relatively low cost and a multitude of gene-altering capabilities have all led to the adoption of the sophisticated and yet simple gene editing system: clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9). The CRISPR/Cas9 system holds promise for the correction of deleterious mutations by taking advantage of the homology directed repair pathway and by supplying a correction template to the affected patient's cells. Currently, this technique is being applied in vitro in human-induced pluripotent stem cells (iPSCs) to correct a variety of severe genetic diseases, but has not as of yet been used in iPSCs derived from patients affected with a lysosomal storage disease (LSD). If adopted into clinical practice, corrected iPSCs derived from cells that originate from the patient themselves could be used for therapeutic amelioration of LSD symptoms without the risks associated with allogeneic stem cell transplantation. CRISPR/Cas9 editing in a patient's cells would overcome the costly, lifelong process associated with currently available treatment methods, including enzyme replacement and substrate reduction therapies. In this review, the overall utility of the CRISPR/Cas9 gene editing technique for treatment of genetic diseases, the potential for the treatment of LSDs and methods currently employed to increase the efficiency of this re-engineered biological system will be discussed.

Novel approach for classifying chemicals according to skin sensitizing potency by non-radioisotopic modification of the local lymph node assay.

PubMed

Takeyoshi, Masahiro; Iida, Kenji; Shiraishi, Keiji; Hoshuyama, Satsuki

2005-01-01

The murine local lymph node assay (LLNA) is currently recognized as a stand-alone sensitization test for determining the sensitizing potential of chemicals, and it has the advantage of yielding a quantitative endpoint that can be used to predict the sensitization potency of chemicals. The EC3 has been proposed as a parameter for classifying chemicals according to the sensitization potency. We previously developed a non-radioisotopic endpoint for the LLNA based on 5-bromo-2'-deoxyuridine (BrdU) incorporation (non-RI LLNA), and we are proposing a new procedure to predict the sensitization potency of chemicals based on comparisons with known human contact allergens. Nine chemicals (i.e. diphencyclopropenone, p-phenylenediamine, glutaraldehyde, cinnamicaldehyde, citral, eugenol, isopropyl myristate, propyleneglycol and hexane) categorized as human contact allergen classes 1-5 were tested by the non-RI LLNA with the following reference allergens: 2,4-dinitrochlorobenzene (DNCB) as a class 1 human contact allergen, isoeugenol as a class 2 human contact allergen and alpha-hexylcinnamic aldehyde (HCA) as a class 3 human contact allergen. Consequently, nine test chemicals were almost assigned to their correct allergen class. The results suggested that the new procedure for non-RI LLNA can provide correct sensitization potency data. Sensitization potency data are useful for evaluating the sensitization risk to humans of exposure to new chemical products. Accordingly, this approach would be an effective modification of LLNA with regard to its experimental design. Moreover, this procedure can be applied also to the standard LLNA with radioisotopes and to other modifications of the LLNA. Copyright 2005 John Wiley & Sons, Ltd.

Gene therapy for inherited muscle diseases: where genetics meets rehabilitation medicine.

PubMed

Braun, Robynne; Wang, Zejing; Mack, David L; Childers, Martin K

2014-11-01

The development of clinical vectors to correct genetic mutations that cause inherited myopathies and related disorders of skeletal muscle is advancing at an impressive rate. Adeno-associated virus vectors are attractive for clinical use because (1) adeno-associated viruses do not cause human disease and (2) these vectors are able to persist for years. New vectors are now becoming available as gene therapy delivery tools, and recent preclinical experiments have demonstrated the feasibility, safety, and efficacy of gene therapy with adeno-associated virus for long-term correction of muscle pathology and weakness in myotubularin-deficient canine and murine disease models. In this review, recent advances in the application of gene therapies to treat inherited muscle disorders are presented, including Duchenne muscular dystrophy and x-linked myotubular myopathy. Potential areas for therapeutic synergies between rehabilitation medicine and genetics are also discussed.

piggyBac transposons expressing full-length human dystrophin enable genetic correction of dystrophic mesoangioblasts.

PubMed

Loperfido, Mariana; Jarmin, Susan; Dastidar, Sumitava; Di Matteo, Mario; Perini, Ilaria; Moore, Marc; Nair, Nisha; Samara-Kuko, Ermira; Athanasopoulos, Takis; Tedesco, Francesco Saverio; Dickson, George; Sampaolesi, Maurilio; VandenDriessche, Thierry; Chuah, Marinee K

2016-01-29

Duchenne muscular dystrophy (DMD) is a genetic neuromuscular disorder caused by the absence of dystrophin. We developed a novel gene therapy approach based on the use of the piggyBac (PB) transposon system to deliver the coding DNA sequence (CDS) of either full-length human dystrophin (DYS: 11.1 kb) or truncated microdystrophins (MD1: 3.6 kb; MD2: 4 kb). PB transposons encoding microdystrophins were transfected in C2C12 myoblasts, yielding 65±2% MD1 and 66±2% MD2 expression in differentiated multinucleated myotubes. A hyperactive PB (hyPB) transposase was then deployed to enable transposition of the large-size PB transposon (17 kb) encoding the full-length DYS and green fluorescence protein (GFP). Stable GFP expression attaining 78±3% could be achieved in the C2C12 myoblasts that had undergone transposition. Western blot analysis demonstrated expression of the full-length human DYS protein in myotubes. Subsequently, dystrophic mesoangioblasts from a Golden Retriever muscular dystrophy dog were transfected with the large-size PB transposon resulting in 50±5% GFP-expressing cells after stable transposition. This was consistent with correction of the differentiated dystrophic mesoangioblasts following expression of full-length human DYS. These results pave the way toward a novel non-viral gene therapy approach for DMD using PB transposons underscoring their potential to deliver large therapeutic genes. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

75 FR 22812 - Guidance for Industry on Tobacco Health Document Submission; Availability; Correction

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-30

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2009-D-0600] Guidance for Industry on Tobacco Health Document Submission; Availability; Correction AGENCY: Food and Drug Administration, HHS. ACTION: Notice; correction. SUMMARY: The Food and Drug Administration (FDA) is correcting a...

An approach to including protein quality when assessing the net contribution of livestock to human food supply.

PubMed

Ertl, P; Knaus, W; Zollitsch, W

2016-11-01

The production of protein from animal sources is often criticized because of the low efficiency of converting plant protein from feeds into protein in the animal products. However, this critique does not consider the fact that large portions of the plant-based proteins fed to animals may be human-inedible and that the quality of animal proteins is usually superior as compared with plant proteins. The aim of the present study was therefore to assess changes in protein quality in the course of the transformation of potentially human-edible plant proteins into animal products via livestock production; data from 30 Austrian dairy farms were used as a case study. A second aim was to develop an approach for combining these changes with quantitative aspects (e.g. with the human-edible feed conversion efficiency (heFCE), defined as kilogram protein in the animal product divided by kilogram potentially human-edible protein in the feeds). Protein quality of potentially human-edible inputs and outputs was assessed using the protein digestibility-corrected amino acid score and the digestible indispensable amino acid score, two methods proposed by the Food and Agriculture Organization of the United Nations to describe the nutritional value of proteins for humans. Depending on the method used, protein scores were between 1.40 and 1.87 times higher for the animal products than for the potentially human-edible plant protein input on a barn-gate level (=protein quality ratio (PQR)). Combining the PQR of 1.87 with the heFCE for the same farms resulted in heFCE×PQR of 2.15. Thus, considering both quantity and quality, the value of the proteins in the animal products for human consumption (in this case in milk and beef) is 2.15 times higher than that of proteins in the potentially human-edible plant protein inputs. The results of this study emphasize the necessity of including protein quality changes resulting from the transformation of plant proteins to animal proteins when evaluating the net contribution of livestock to the human food supply. Furthermore, these differences in protein quality might also need to be considered when choosing a functional unit for the assessment of environmental impacts of the production of different proteins.

Better band gaps with asymptotically corrected local exchange potentials

NASA Astrophysics Data System (ADS)

Singh, Prashant; Harbola, Manoj K.; Hemanadhan, M.; Mookerjee, Abhijit; Johnson, D. D.

2016-02-01

We formulate a spin-polarized van Leeuwen and Baerends (vLB) correction to the local density approximation (LDA) exchange potential [R. van Leeuwen and E. J. Baerends, Phys. Rev. A 49, 2421 (1994), 10.1103/PhysRevA.49.2421] that enforces the ionization potential (IP) theorem following T. Stein et al. [Phys. Rev. Lett. 105, 266802 (2010), 10.1103/PhysRevLett.105.266802]. For electronic-structure problems, the vLB correction replicates the behavior of exact-exchange potentials, with improved scaling and well-behaved asymptotics, but with the computational cost of semilocal functionals. The vLB + IP correction produces a large improvement in the eigenvalues over those from the LDA due to correct asymptotic behavior and atomic shell structures, as shown in rare-gas, alkaline-earth, zinc-based oxides, alkali halides, sulfides, and nitrides. In half-Heusler alloys, this asymptotically corrected LDA reproduces the spin-polarized properties correctly, including magnetism and half-metallicity. We also consider finite-sized systems [e.g., ringed boron nitride (B12N12 ) and graphene (C24)] to emphasize the wide applicability of the method.

Better band gaps with asymptotically corrected local exchange potentials

DOE PAGES

Singh, Prashant; Harbola, Manoj K.; Hemanadhan, M.; ...

2016-02-22

In this study, we formulate a spin-polarized van Leeuwen and Baerends (vLB) correction to the local density approximation (LDA) exchange potential [R. van Leeuwen and E. J. Baerends, Phys. Rev. A 49, 2421 (1994)] that enforces the ionization potential (IP) theorem following T. Stein et al. [Phys. Rev. Lett. 105, 266802 (2010)]. For electronic-structure problems, the vLB correction replicates the behavior of exact-exchange potentials, with improved scaling and well-behaved asymptotics, but with the computational cost of semilocal functionals. The vLB + IP correction produces a large improvement in the eigenvalues over those from the LDA due to correct asymptotic behaviormore » and atomic shell structures, as shown in rare-gas, alkaline-earth, zinc-based oxides, alkali halides, sulfides, and nitrides. In half-Heusler alloys, this asymptotically corrected LDA reproduces the spin-polarized properties correctly, including magnetism and half-metallicity. We also consider finite-sized systems [e.g., ringed boron nitride (B 12N 12) and graphene (C 24)] to emphasize the wide applicability of the method.« less

Fundamentals of translational neuroscience in toxicologic pathology: optimizing the value of animal data for human risk assessment.

PubMed

Morrison, James P; Sharma, Alok K; Rao, Deepa; Pardo, Ingrid D; Garman, Robert H; Kaufmann, Wolfgang; Bolon, Brad

2015-01-01

A half-day Society of Toxicologic Pathology continuing education course on "Fundamentals of Translational Neuroscience in Toxicologic Pathology" presented some current major issues faced when extrapolating animal data regarding potential neurological consequences to assess potential human outcomes. Two talks reviewed functional-structural correlates in rodent and nonrodent mammalian brains needed to predict behavioral consequences of morphologic changes in discrete neural cell populations. The third lecture described practical steps for ensuring that specimens from rodent developmental neurotoxicity tests will be processed correctly to produce highly homologous sections. The fourth talk detailed demographic factors (e.g., species, strain, sex, and age); physiological traits (body composition, brain circulation, pharmacokinetic/pharmacodynamic patterns, etc.); and husbandry influences (e.g., group housing) known to alter the effects of neuroactive agents. The last presentation discussed the appearance, unknown functional effects, and potential relevance to humans of polyethylene glycol (PEG)-associated vacuoles within the choroid plexus epithelium of animals. Speakers provided real-world examples of challenges with data extrapolation among species or with study design considerations that may impact the interpretability of results. Translational neuroscience will be bolstered in the future as less invasive and/or more quantitative techniques are devised for linking overt functional deficits to subtle anatomic and chemical lesions. © 2014 by The Author(s).

Theoretical study of zeatin - A plant hormone and potential drug for neural diseases - On the basis of DFT, MP2 and target docking

NASA Astrophysics Data System (ADS)

Liu, Xueping; Bereźniak, Tomasz; Panek, Jarosław Jan; Jezierska-Mazzarello, Aneta

2013-02-01

Zeatin, a cytokinin of the adenine family, originally isolated from Zea mays L., exhibits also bioeffects towards human cells: it is a potent acetylcholinesterase inhibitor and can potentially inhibit amyloid β-protein formation. The role of zeatin in neural disease treatment is yet to be established. This computational study describes a hierarchy of interactions between zeatin and a receptor, a protein from the nodulin family. DFT in hybrid and dispersion-corrected form as well as MP2 approaches were used to derive interaction energies. Docking procedure was employed to investigate the role of selected interaction for anchoring the ligand.

Organelle Redox of CF and CFTR-Corrected Airway Epithelia

PubMed Central

Schwarzer, Christian; Illek, Beate; Suh, Jung H.; Remington, S. James; Fischer, Horst; Machen, Terry E.

2014-01-01

In cystic fibrosis reduced CFTR function may alter redox properties of airway epithelial cells. Redox-sensitive GFP (roGFP1) and imaging microscopy were used to measure redox potentials of cytosol, ER, mitochondria and cell surface of cystic fibrosis nasal epithelial cells and CFTR-corrected cells. We also measured glutathione and cysteine thiol redox states in cell lysates and apical fluids to provide coverage over a range of redox potentials and environments that might be affected by CFTR. As measured with roGFP1, redox potentials at the cell surface (~ -207 ±8 mV) and in the ER (~ -217 ±1 mV) and rates of regulation of the apical fluid and ER lumen following DTT treatment were similar for CF and CFTR-corrected cells. CF and CFTR-corrected cells had similar redox potentials in mitochondria (-344 ±9 mV) and cytosol (-322 ±7 mV). Oxidation of carboxy-dichlorodihydrofluoresceindiacetate and of apical Amplex Red occurred at equal rates in CF and CFTR-corrected cells. Glutathione and cysteine redox couples in cell lysates and apical fluid were equal in CF and CFTR-corrected cells. These quantitative estimates of organelle redox potentials combined with apical and cell measurements using small molecule couples confirmed there were no differences in redox properties of CF and CFTR-corrected cells. PMID:17603939

The radiation shielding potential of CI and CM chondrites

NASA Astrophysics Data System (ADS)

Pohl, Leos; Britt, Daniel T.

2017-03-01

Galactic Cosmic Rays (GCRs) and Solar Energetic Particles (SEPs) pose a serious limit on the duration of deep space human missions. A shield composed of a bulk mass of material in which the incident particles deposit their energy is the simplest way to attenuate the radiation. The cost of bringing the sufficient mass from the Earth's surface is prohibitive. The shielding properties of asteroidal material, which is readily available in space, are investigated. Solution of Bethe's equation is implemented for incident protons and the application in composite materials and the significance of various correction terms are discussed; the density correction is implemented. The solution is benchmarked and shows good agreement with the results in literature which implement more correction terms within the energy ranges considered. The shielding properties of CI and CM asteroidal taxonomy groups and major asteroidal minerals are presented in terms of stopping force. The results show that CI and CM chondrites have better stopping properties than Aluminium. Beneficiation is discussed and is shown to have a significant effect on the stopping power.

Cortico-muscular coherence on artifact corrected EEG-EMG data recorded with a MRI scanner.

PubMed

Muthuraman, M; Galka, A; Hong, V N; Heute, U; Deuschl, G; Raethjen, J

2013-01-01

Simultaneous recording of electroencephalogram (EEG) and electromyogram (EMG) with magnetic resonance imaging (MRI) provides great potential for studying human brain activity with high temporal and spatial resolution. But, due to the MRI, the recorded signals are contaminated with artifacts. The correction of these artifacts is important to use these signals for further spectral analysis. The coherence can reveal the cortical representation of peripheral muscle signal in particular motor tasks, e.g. finger movements. The artifact correction of these signals was done by two different algorithms the Brain vision analyzer (BVA) and the Matlab FMRIB plug-in for EEGLAB. The Welch periodogram method was used for estimating the cortico-muscular coherence. Our analysis revealed coherence with a frequency of 5Hz in the contralateral side of the brain. The entropy is estimated for the calculated coherence to get the distribution of coherence in the scalp. The significance of the paper is to identify the optimal algorithm to rectify the MR artifacts and as a first step to use both these signals EEG and EMG in conjunction with MRI for further studies.

Correction of mutant Fanconi anemia gene by homologous recombination in human hematopoietic cells using adeno-associated virus vector.

PubMed

Paiboonsukwong, Kittiphong; Ohbayashi, Fumi; Shiiba, Haruka; Aizawa, Emi; Yamashita, Takayuki; Mitani, Kohnosuke

2009-11-01

Adeno-associated virus (AAV) vectors have been shown to correct a variety of mutations in human cells by homologous recombination (HR) at high rates, which can overcome insertional mutagenesis and transgene silencing, two of the major hurdles in conventional gene addition therapy of inherited diseases. We examined an ability of AAV vectors to repair a mutation in human hematopoietic cells by HR. We infected a human B-lymphoblastoid cell line (BCL) derived from a normal subject with an AAV, which disrupts the hypoxanthine phosphoribosyl transferase1 (HPRT1) locus, to measure the frequency of AAV-mediated HR in BCL cells. We subsequently constructed an AAV vector encoding the normal sequences from the Fanconi anemia group A (FANCA) locus to correct a mutation in the gene in BCL derived from a FANCA patient. Under optimal conditions, approximately 50% of BCL cells were transduced with an AAV serotype 2 (AAV-2) vector. In FANCA BCL cells, up to 0.016% of infected cells were gene-corrected by HR. AAV-mediated restoration of normal genotypic and phenotypic characteristics in FANCA-mutant cells was confirmed at the DNA, protein and functional levels. The results obtained in the present study indicate that AAV vectors may be applicable for gene correction therapy of inherited hematopoietic disorders.

Calibration and temperature correction of heat dissipation matric potential sensors

USGS Publications Warehouse

Flint, A.L.; Campbell, G.S.; Ellett, K.M.; Calissendorff, C.

2002-01-01

This paper describes how heat dissipation sensors, used to measure soil water matric potential, were analyzed to develop a normalized calibration equation and a temperature correction method. Inference of soil matric potential depends on a correlation between the variable thermal conductance of the sensor's porous ceramic and matric poten-tial. Although this correlation varies among sensors, we demonstrate a normalizing procedure that produces a single calibration relationship. Using sensors from three sources and different calibration methods, the normalized calibration resulted in a mean absolute error of 23% over a matric potential range of -0.01 to -35 MPa. Because the thermal conductivity of variably saturated porous media is temperature dependent, a temperature correction is required for application of heat dissipation sensors in field soils. A temperature correction procedure is outlined that reduces temperature dependent errors by 10 times, which reduces the matric potential measurement errors by more than 30%. The temperature dependence is well described by a thermal conductivity model that allows for the correction of measurements at any temperature to measurements at the calibration temperature.

21 CFR 806.2 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-04-01

... FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES MEDICAL DEVICES; REPORTS OF CORRECTIONS AND REMOVALS General Provisions § 806.2 Definitions. As used in... device subject to correction or removal. (d) Correction means the repair, modification, adjustment...

21 CFR 806.2 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-04-01

... FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES MEDICAL DEVICES; REPORTS OF CORRECTIONS AND REMOVALS General Provisions § 806.2 Definitions. As used in... device subject to correction or removal. (d) Correction means the repair, modification, adjustment...

77 FR 4228 - Technical Amendments and Corrections to DEA Regulations

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-27

...'' to be ``Service''; In Sec. 1313.31(b)(5), correcting the word ``new'' to be ``net''; In Sec. 1314.45... of Health and Human Services for such administration. If any person prescribes, dispenses, or distributes such steroid for human use, the person shall be considered to have prescribed, dispensed, or...

Evaluating the Performance Diagnostic Checklist-Human Services to Assess Incorrect Error-Correction Procedures by Preschool Paraprofessionals

ERIC Educational Resources Information Center

Bowe, Melissa; Sellers, Tyra P.

2018-01-01

The Performance Diagnostic Checklist-Human Services (PDC-HS) has been used to assess variables contributing to undesirable staff performance. In this study, three preschool teachers completed the PDC-HS to identify the factors contributing to four paraprofessionals' inaccurate implementation of error-correction procedures during discrete trial…

Increasing consistency of disease biomarker prediction across datasets.

PubMed

Chikina, Maria D; Sealfon, Stuart C

2014-01-01

Microarray studies with human subjects often have limited sample sizes which hampers the ability to detect reliable biomarkers associated with disease and motivates the need to aggregate data across studies. However, human gene expression measurements may be influenced by many non-random factors such as genetics, sample preparations, and tissue heterogeneity. These factors can contribute to a lack of agreement among related studies, limiting the utility of their aggregation. We show that it is feasible to carry out an automatic correction of individual datasets to reduce the effect of such 'latent variables' (without prior knowledge of the variables) in such a way that datasets addressing the same condition show better agreement once each is corrected. We build our approach on the method of surrogate variable analysis but we demonstrate that the original algorithm is unsuitable for the analysis of human tissue samples that are mixtures of different cell types. We propose a modification to SVA that is crucial to obtaining the improvement in agreement that we observe. We develop our method on a compendium of multiple sclerosis data and verify it on an independent compendium of Parkinson's disease datasets. In both cases, we show that our method is able to improve agreement across varying study designs, platforms, and tissues. This approach has the potential for wide applicability to any field where lack of inter-study agreement has been a concern.

Correction of β-thalassemia mutant by base editor in human embryos.

PubMed

Liang, Puping; Ding, Chenhui; Sun, Hongwei; Xie, Xiaowei; Xu, Yanwen; Zhang, Xiya; Sun, Ying; Xiong, Yuanyan; Ma, Wenbin; Liu, Yongxiang; Wang, Yali; Fang, Jianpei; Liu, Dan; Songyang, Zhou; Zhou, Canquan; Huang, Junjiu

2017-11-01

β-Thalassemia is a global health issue, caused by mutations in the HBB gene. Among these mutations, HBB -28 (A>G) mutations is one of the three most common mutations in China and Southeast Asia patients with β-thalassemia. Correcting this mutation in human embryos may prevent the disease being passed onto future generations and cure anemia. Here we report the first study using base editor (BE) system to correct disease mutant in human embryos. Firstly, we produced a 293T cell line with an exogenous HBB -28 (A>G) mutant fragment for gRNAs and targeting efficiency evaluation. Then we collected primary skin fibroblast cells from a β-thalassemia patient with HBB -28 (A>G) homozygous mutation. Data showed that base editor could precisely correct HBB -28 (A>G) mutation in the patient's primary cells. To model homozygous mutation disease embryos, we constructed nuclear transfer embryos by fusing the lymphocyte or skin fibroblast cells with enucleated in vitro matured (IVM) oocytes. Notably, the gene correction efficiency was over 23.0% in these embryos by base editor. Although these embryos were still mosaic, the percentage of repaired blastomeres was over 20.0%. In addition, we found that base editor variants, with narrowed deamination window, could promote G-to-A conversion at HBB -28 site precisely in human embryos. Collectively, this study demonstrated the feasibility of curing genetic disease in human somatic cells and embryos by base editor system.

Emerging genetic therapies to treat Duchenne muscular dystrophy

PubMed Central

Nelson, Stanley F.; Crosbie, Rachelle H.; Miceli, M. Carrie; Spencer, Melissa J.

2010-01-01

Purpose of review Duchenne muscular dystrophy is a progressive muscle degenerative disease caused by dystrophin mutations. The purpose of this review is to highlight two emerging therapies designed to repair the primary genetic defect, called `exon skipping' and `nonsense codon suppression'. Recent findings A drug, PTC124, was identified that suppresses nonsense codon translation termination. PTC124 can lead to restoration of some dystrophin expression in human Duchenne muscular dystrophy muscles with mutations resulting in premature stops. Two drugs developed for exon skipping, PRO051 and AVI-4658, result in the exclusion of exon 51 from mature mRNA. They can restore the translational reading frame to dystrophin transcripts from patients with a particular subset of dystrophin gene deletions and lead to some restoration of dystrophin expression in affected boys' muscle in vivo. Both approaches have concluded phase I trials with no serious adverse events. Summary These novel therapies that act to correct the primary genetic defect of dystrophin deficiency are among the first generation of therapies tailored to correct specific mutations in humans. Thus, they represent paradigm forming approaches to personalized medicine with the potential to lead to life changing treatment for those affected by Duchenne muscular dystrophy. PMID:19745732

The case for applying tissue engineering methodologies to instruct human organoid morphogenesis.

PubMed

Marti-Figueroa, Carlos R; Ashton, Randolph S

2017-05-01

Three-dimensional organoids derived from human pluripotent stem cell (hPSC) derivatives have become widely used in vitro models for studying development and disease. Their ability to recapitulate facets of normal human development during in vitro morphogenesis produces tissue structures with unprecedented biomimicry. Current organoid derivation protocols primarily rely on spontaneous morphogenesis processes to occur within 3-D spherical cell aggregates with minimal to no exogenous control. This yields organoids containing microscale regions of biomimetic tissues, but at the macroscale (i.e. 100's of microns to millimeters), the organoids' morphology, cytoarchitecture, and cellular composition are non-biomimetic and variable. The current lack of control over in vitro organoid morphogenesis at the microscale induces aberrations at the macroscale, which impedes realization of the technology's potential to reproducibly form anatomically correct human tissue units that could serve as optimal human in vitro models and even transplants. Here, we review tissue engineering methodologies that could be used to develop powerful approaches for instructing multiscale, 3-D human organoid morphogenesis. Such technological mergers are critically needed to harness organoid morphogenesis as a tool for engineering functional human tissues with biomimetic anatomy and physiology. Human PSC-derived 3-D organoids are revolutionizing the biomedical sciences. They enable the study of development and disease within patient-specific genetic backgrounds and unprecedented biomimetic tissue microenvironments. However, their uncontrolled, spontaneous morphogenesis at the microscale yields inconsistences in macroscale organoid morphology, cytoarchitecture, and cellular composition that limits their standardization and application. Integration of tissue engineering methods with organoid derivation protocols could allow us to harness their potential by instructing standardized in vitro morphogenesis to generate organoids with biomimicry at all scales. Such advancements would enable the use of organoids as a basis for 'next-generation' tissue engineering of functional, anatomically mimetic human tissues and potentially novel organ transplants. Here, we discuss critical aspects of organoid morphogenesis where application of innovative tissue engineering methodologies would yield significant advancement towards this goal. Copyright © 2017. Published by Elsevier Ltd.

In Vitro T-Cell Generation From Adult, Embryonic, and Induced Pluripotent Stem Cells: Many Roads to One Destination.

PubMed

Smith, Michelle J; Webber, Beau R; Mohtashami, Mahmood; Stefanski, Heather E; Zúñiga-Pflücker, Juan Carlos; Blazar, Bruce R

2015-11-01

T lymphocytes are critical mediators of the adaptive immune system and have the capacity to serve as therapeutic agents in the areas of transplant and cancer immunotherapy. While T cells can be isolated and expanded from patients, T cells derived in vitro from both hematopoietic stem/progenitor cells (HSPCs) and human pluripotent stem cells (hPSCs) offer great potential advantages in generating a self-renewing source of T cells that can be readily genetically modified. T-cell differentiation in vivo is a complex process requiring tightly regulated signals; providing the correct signals in vitro to induce T-cell lineage commitment followed by their development into mature, functional, single positive T cells, is similarly complex. In this review, we discuss current methods for the in vitro derivation of T cells from murine and human HSPCs and hPSCs that use feeder-cell and feeder-cell-free systems. Furthermore, we explore their potential for adoption for use in T-cell-based therapies. © 2015 AlphaMed Press.

Quantification of regenerative potential in primary human mammary epithelial cells.

PubMed

Linnemann, Jelena R; Miura, Haruko; Meixner, Lisa K; Irmler, Martin; Kloos, Uwe J; Hirschi, Benjamin; Bartsch, Harald S; Sass, Steffen; Beckers, Johannes; Theis, Fabian J; Gabka, Christian; Sotlar, Karl; Scheel, Christina H

2015-09-15

We present an organoid regeneration assay in which freshly isolated human mammary epithelial cells are cultured in adherent or floating collagen gels, corresponding to a rigid or compliant matrix environment. In both conditions, luminal progenitors form spheres, whereas basal cells generate branched ductal structures. In compliant but not rigid collagen gels, branching ducts form alveoli at their tips, express basal and luminal markers at correct positions, and display contractility, which is required for alveologenesis. Thereby, branched structures generated in compliant collagen gels resemble terminal ductal-lobular units (TDLUs), the functional units of the mammary gland. Using the membrane metallo-endopeptidase CD10 as a surface marker enriches for TDLU formation and reveals the presence of stromal cells within the CD49f(hi)/EpCAM(-) population. In summary, we describe a defined in vitro assay system to quantify cells with regenerative potential and systematically investigate their interaction with the physical environment at distinct steps of morphogenesis. © 2015. Published by The Company of Biologists Ltd.

[A wireless smart home system based on brain-computer interface of steady state visual evoked potential].

PubMed

Zhao, Li; Xing, Xiao; Guo, Xuhong; Liu, Zehua; He, Yang

2014-10-01

Brain-computer interface (BCI) system is a system that achieves communication and control among humans and computers and other electronic equipment with the electroencephalogram (EEG) signals. This paper describes the working theory of the wireless smart home system based on the BCI technology. We started to get the steady-state visual evoked potential (SSVEP) using the single chip microcomputer and the visual stimulation which composed by LED lamp to stimulate human eyes. Then, through building the power spectral transformation on the LabVIEW platform, we processed timely those EEG signals under different frequency stimulation so as to transfer them to different instructions. Those instructions could be received by the wireless transceiver equipment to control the household appliances and to achieve the intelligent control towards the specified devices. The experimental results showed that the correct rate for the 10 subjects reached 100%, and the control time of average single device was 4 seconds, thus this design could totally achieve the original purpose of smart home system.

Accurate determination of brain metabolite concentrations using ERETIC as external reference.

PubMed

Zoelch, Niklaus; Hock, Andreas; Heinzer-Schweizer, Susanne; Avdievitch, Nikolai; Henning, Anke

2017-08-01

Magnetic Resonance Spectroscopy (MRS) can provide in vivo metabolite concentrations in standard concentration units if a reliable reference signal is available. For 1 H MRS in the human brain, typically the signal from the tissue water is used as the (internal) reference signal. However, a concentration determination based on the tissue water signal most often requires a reliable estimate of the water concentration present in the investigated tissue. Especially in clinically interesting cases, this estimation might be difficult. To avoid assumptions about the water in the investigated tissue, the Electric REference To access In vivo Concentrations (ERETIC) method has been proposed. In this approach, the metabolite signal is compared with a reference signal acquired in a phantom and potential coil-loading differences are corrected using a synthetic reference signal. The aim of this study, conducted with a transceiver quadrature head coil, was to increase the accuracy of the ERETIC method by correcting the influence of spatial B 1 inhomogeneities and to simplify the quantification with ERETIC by incorporating an automatic phase correction for the ERETIC signal. Transmit field ( B1+) differences are minimized with a volume-selective power optimization, whereas reception sensitivity changes are corrected using contrast-minimized images of the brain and by adapting the voxel location in the phantom measurement closely to the position measured in vivo. By applying the proposed B 1 correction scheme, the mean metabolite concentrations determined with ERETIC in 21 healthy subjects at three different positions agree with concentrations derived with the tissue water signal as reference. In addition, brain water concentrations determined with ERETIC were in agreement with estimations derived using tissue segmentation and literature values for relative water densities. Based on the results, the ERETIC method presented here is a valid tool to derive in vivo metabolite concentration, with potential advantages compared with internal water referencing in diseased tissue. Copyright © 2017 John Wiley & Sons, Ltd.

Increased folding and channel activity of a rare cystic fibrosis mutant with CFTR modulators

PubMed Central

Grove, Diane E.; Houck, Scott A.

2011-01-01

Cystic fibrosis (CF) is a lethal recessive genetic disease caused by mutations in the CFTR gene. The gene product is a PKA-regulated anion channel that is important for fluid and electrolyte transport in the epithelia of lung, gut, and ducts of the pancreas and sweat glands. The most common CFTR mutation, ΔF508, causes a severe, but correctable, folding defect and gating abnormality, resulting in negligible CFTR function and disease. There are also a large number of rare CF-related mutations where disease is caused by CFTR misfolding. Yet the extent to which defective biogenesis of these CFTR mutants can be corrected is not clear. CFTRV232D is one such mutant that exhibits defective folding and trafficking. CFTRΔF508 misfolding is difficult to correct, but defective biogenesis of CFTRV232D is corrected to near wild-type levels by small-molecule folding correctors in development as CF therapeutics. To determine if CFTRV232D protein is competent as a Cl− channel, we utilized single-channel recordings from transfected human embryonic kidney (HEK-293) cells. After PKA stimulation, CFTRV232D channels were detected in patches with a unitary Cl− conductance indistinguishable from that of CFTR. Yet the frequency of detecting CFTRV232D channels was reduced to ∼20% of patches compared with 60% for CFTR. The folding corrector Corr-4a increased the CFTRV232D channel detection rate and activity to levels similar to CFTR. CFTRV232D-corrected channels were inhibited with CFTRinh-172 and stimulated fourfold by the CFTR channel potentiator VRT-532. These data suggest that CF patients with rare mutations that cause CFTR misfolding, such as CFTRV232D, may benefit from treatment with folding correctors and channel potentiators in development to restore CFTRΔF508 function. PMID:21642448

Human rights and correctional health policy: a view from Europe.

PubMed

Rogan, Mary

2017-03-13

Purpose Correctional healthcare should promote the protection of human rights. The purpose of this paper is to bring a discussion of human rights into debates on how such policy should be best organized. Design/methodology/approach The paper achieves its aim by providing an analysis of European prison law and policy in the area of prison health, through assessing decisions of the European Court of Human Rights, as well as policies created by the European Committee for the Prevention of Torture. Findings The paper describes the position of the European Court of Human Rights on the topics of access to healthcare, ill health and release from prison, mental illness in prison, and the duty to provide rehabilitative programming for those seeking to reduce their level of "risk." It also argues that human rights law can be a source of practical reform, and that legal frameworks have much to offer healthcare leaders seeking to uphold the dignity of those in their care. Originality/value This paper will provide a rare example of the engagement of human rights law with correctional health policy. It provides practical recommendations arising out of an analysis of European human rights law in the area of prisons.

Psychiatric education in the correctional setting: challenges and opportunities.

PubMed

Holoyda, Brian J; Scott, Charles L

2017-02-01

As the need for mental healthcare services within correctional settings in the US increases, so does the need for a mental health workforce that is motivated to work within such systems. One potentially effective method by which to increase the number of psychiatrists working in jails, prisons, and parole clinics is to provide exposure to these environments during their training. Correctional settings can serve as unique training sites for medical students and psychiatric residents and fellows. Such training experiences can provide a host of benefits to both trainees and staff within the correctional mental health system. Alongside many potential benefits exist substantial potential barriers to coordinating correctional training experiences, including both programme directors' and residents' concerns regarding safety and enjoyment and negative perceptions of inmate and prisoner patients. The establishment of academic affiliations with correctional institutions and didactic instruction on commonly encountered clinical issues with inmate populations may be methods of diffusing these concerns. Improving residents' and fellows' training experiences offers a hope for increasing the attractiveness of a career in correctional psychiatry.

Reliability of bloodhounds in criminal investigations.

PubMed

Harvey, Lisa M; Harvey, Jeffrey W

2003-07-01

Anecdotal evidence and legend have suggested that bloodhounds are capable of trailing and alerting to a human by his or her individual scent. This same evidence may be presented to a court of law in order to accuse a particular suspect or suspects of a crime. There is little to no scientific evidence confirming the bloodhound's ability to trail and discriminate the scent of different individual humans. Eight bloodhounds (3 novice and 5 veteran), trained in human scent discrimination were used to determine the reliability of evidence, garnered through the use of bloodhounds, in a court of law. These dogs were placed on trails in an environment that simulated real-life scenarios. Results indicate that a veteran bloodhound can trail and correctly identify a person under various conditions. These data suggest that the potential error rate of a veteran bloodhound-handler team is low and can be a useful tool for law enforcement personnel.

Distortion Correction of OCT Images of the Crystalline Lens: GRIN Approach

PubMed Central

Siedlecki, Damian; de Castro, Alberto; Gambra, Enrique; Ortiz, Sergio; Borja, David; Uhlhorn, Stephen; Manns, Fabrice; Marcos, Susana; Parel, Jean-Marie

2012-01-01

Purpose To propose a method to correct Optical Coherence Tomography (OCT) images of posterior surface of the crystalline lens incorporating its gradient index (GRIN) distribution and explore its possibilities for posterior surface shape reconstruction in comparison to existing methods of correction. Methods 2-D images of 9 human lenses were obtained with a time-domain OCT system. The shape of the posterior lens surface was corrected using the proposed iterative correction method. The parameters defining the GRIN distribution used for the correction were taken from a previous publication. The results of correction were evaluated relative to the nominal surface shape (accessible in vitro) and compared to the performance of two other existing methods (simple division, refraction correction: assuming a homogeneous index). Comparisons were made in terms of posterior surface radius, conic constant, root mean square, peak to valley and lens thickness shifts from the nominal data. Results Differences in the retrieved radius and conic constant were not statistically significant across methods. However, GRIN distortion correction with optimal shape GRIN parameters provided more accurate estimates of the posterior lens surface, in terms of RMS and peak values, with errors less than 6μm and 13μm respectively, on average. Thickness was also more accurately estimated with the new method, with a mean discrepancy of 8μm. Conclusions The posterior surface of the crystalline lens and lens thickness can be accurately reconstructed from OCT images, with the accuracy improving with an accurate model of the GRIN distribution. The algorithm can be used to improve quantitative knowledge of the crystalline lens from OCT imaging in vivo. Although the improvements over other methods are modest in 2-D, it is expected that 3-D imaging will fully exploit the potential of the technique. The method will also benefit from increasing experimental data of GRIN distribution in the lens of larger populations. PMID:22466105

Distortion correction of OCT images of the crystalline lens: gradient index approach.

PubMed

Siedlecki, Damian; de Castro, Alberto; Gambra, Enrique; Ortiz, Sergio; Borja, David; Uhlhorn, Stephen; Manns, Fabrice; Marcos, Susana; Parel, Jean-Marie

2012-05-01

To propose a method to correct optical coherence tomography (OCT) images of posterior surface of the crystalline lens incorporating its gradient index (GRIN) distribution and explore its possibilities for posterior surface shape reconstruction in comparison to existing methods of correction. Two-dimensional images of nine human lenses were obtained with a time-domain OCT system. The shape of the posterior lens surface was corrected using the proposed iterative correction method. The parameters defining the GRIN distribution used for the correction were taken from a previous publication. The results of correction were evaluated relative to the nominal surface shape (accessible in vitro) and compared with the performance of two other existing methods (simple division, refraction correction: assuming a homogeneous index). Comparisons were made in terms of posterior surface radius, conic constant, root mean square, peak to valley, and lens thickness shifts from the nominal data. Differences in the retrieved radius and conic constant were not statistically significant across methods. However, GRIN distortion correction with optimal shape GRIN parameters provided more accurate estimates of the posterior lens surface in terms of root mean square and peak values, with errors <6 and 13 μm, respectively, on average. Thickness was also more accurately estimated with the new method, with a mean discrepancy of 8 μm. The posterior surface of the crystalline lens and lens thickness can be accurately reconstructed from OCT images, with the accuracy improving with an accurate model of the GRIN distribution. The algorithm can be used to improve quantitative knowledge of the crystalline lens from OCT imaging in vivo. Although the improvements over other methods are modest in two dimension, it is expected that three-dimensional imaging will fully exploit the potential of the technique. The method will also benefit from increasing experimental data of GRIN distribution in the lens of larger populations.

A Simple Noise Correction Scheme for Diffusional Kurtosis Imaging

PubMed Central

Glenn, G. Russell; Tabesh, Ali; Jensen, Jens H.

2014-01-01

Purpose Diffusional kurtosis imaging (DKI) is sensitive to the effects of signal noise due to strong diffusion weightings and higher order modeling of the diffusion weighted signal. A simple noise correction scheme is proposed to remove the majority of the noise bias in the estimated diffusional kurtosis. Methods Weighted linear least squares (WLLS) fitting together with a voxel-wise, subtraction-based noise correction from multiple, independent acquisitions are employed to reduce noise bias in DKI data. The method is validated in phantom experiments and demonstrated for in vivo human brain for DKI-derived parameter estimates. Results As long as the signal-to-noise ratio (SNR) for the most heavily diffusion weighted images is greater than 2.1, errors in phantom diffusional kurtosis estimates are found to be less than 5 percent with noise correction, but as high as 44 percent for uncorrected estimates. In human brain, noise correction is also shown to improve diffusional kurtosis estimates derived from measurements made with low SNR. Conclusion The proposed correction technique removes the majority of noise bias from diffusional kurtosis estimates in noisy phantom data and is applicable to DKI of human brain. Features of the method include computational simplicity and ease of integration into standard WLLS DKI post-processing algorithms. PMID:25172990

Gulls identified as major source of fecal pollution in coastal waters: a microbial source tracking study.

PubMed

Araújo, Susana; Henriques, Isabel S; Leandro, Sérgio Miguel; Alves, Artur; Pereira, Anabela; Correia, António

2014-02-01

Gulls were reported as sources of fecal pollution in coastal environments and potential vectors of human infections. Microbial source tracking (MST) methods were rarely tested to identify this pollution origin. This study was conducted to ascertain the source of water fecal contamination in the Berlenga Island, Portugal. A total of 169 Escherichia coli isolates from human sewage, 423 isolates from gull feces and 334 water isolates were analyzed by BOX-PCR. An average correct classification of 79.3% was achieved. When an 85% similarity cutoff was applied 24% of water isolates were present in gull feces against 2.7% detected in sewage. Jackknifing resulted in 29.3% of water isolates classified as gull, and 10.8% classified as human. Results indicate that gulls constitute a major source of water contamination in the Berlenga Island. This study validated a methodology to differentiate human and gull fecal pollution sources in a real case of a contaminated beach. © 2013.

Improved volumetric measurement of brain structure with a distortion correction procedure using an ADNI phantom.

PubMed

Maikusa, Norihide; Yamashita, Fumio; Tanaka, Kenichiro; Abe, Osamu; Kawaguchi, Atsushi; Kabasawa, Hiroyuki; Chiba, Shoma; Kasahara, Akihiro; Kobayashi, Nobuhisa; Yuasa, Tetsuya; Sato, Noriko; Matsuda, Hiroshi; Iwatsubo, Takeshi

2013-06-01

Serial magnetic resonance imaging (MRI) images acquired from multisite and multivendor MRI scanners are widely used in measuring longitudinal structural changes in the brain. Precise and accurate measurements are important in understanding the natural progression of neurodegenerative disorders such as Alzheimer's disease. However, geometric distortions in MRI images decrease the accuracy and precision of volumetric or morphometric measurements. To solve this problem, the authors suggest a commercially available phantom-based distortion correction method that accommodates the variation in geometric distortion within MRI images obtained with multivendor MRI scanners. The authors' method is based on image warping using a polynomial function. The method detects fiducial points within a phantom image using phantom analysis software developed by the Mayo Clinic and calculates warping functions for distortion correction. To quantify the effectiveness of the authors' method, the authors corrected phantom images obtained from multivendor MRI scanners and calculated the root-mean-square (RMS) of fiducial errors and the circularity ratio as evaluation values. The authors also compared the performance of the authors' method with that of a distortion correction method based on a spherical harmonics description of the generic gradient design parameters. Moreover, the authors evaluated whether this correction improves the test-retest reproducibility of voxel-based morphometry in human studies. A Wilcoxon signed-rank test with uncorrected and corrected images was performed. The root-mean-square errors and circularity ratios for all slices significantly improved (p < 0.0001) after the authors' distortion correction. Additionally, the authors' method was significantly better than a distortion correction method based on a description of spherical harmonics in improving the distortion of root-mean-square errors (p < 0.001 and 0.0337, respectively). Moreover, the authors' method reduced the RMS error arising from gradient nonlinearity more than gradwarp methods. In human studies, the coefficient of variation of voxel-based morphometry analysis of the whole brain improved significantly from 3.46% to 2.70% after distortion correction of the whole gray matter using the authors' method (Wilcoxon signed-rank test, p < 0.05). The authors proposed a phantom-based distortion correction method to improve reproducibility in longitudinal structural brain analysis using multivendor MRI. The authors evaluated the authors' method for phantom images in terms of two geometrical values and for human images in terms of test-retest reproducibility. The results showed that distortion was corrected significantly using the authors' method. In human studies, the reproducibility of voxel-based morphometry analysis for the whole gray matter significantly improved after distortion correction using the authors' method.

Corrective Action Investigation Plan for Corrective Action Unit 410: Waste Disposal Trenches, Tonopah Test Range, Nevada, Revision 0 (includes ROTCs 1, 2, and 3)

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

NNSA /NV

This Corrective Action Investigation Plan contains the U.S. Department of Energy, National Nuclear Security Administration Nevada Operations Office's approach to collect the data necessary to evaluate corrective action alternatives appropriate for the closure of Corrective Action Unit (CAU) 410 under the Federal Facility Agreement and Consent Order. Corrective Action Unit 410 is located on the Tonopah Test Range (TTR), which is included in the Nevada Test and Training Range (formerly the Nellis Air Force Range) approximately 140 miles northwest of Las Vegas, Nevada. This CAU is comprised of five Corrective Action Sites (CASs): TA-19-002-TAB2, Debris Mound; TA-21-003-TANL, Disposal Trench; TA-21-002-TAAL,more » Disposal Trench; 09-21-001-TA09, Disposal Trenches; 03-19-001, Waste Disposal Site. This CAU is being investigated because contaminants may be present in concentrations that could potentially pose a threat to human health and/or the environment, and waste may have been disposed of with out appropriate controls. Four out of five of these CASs are the result of weapons testing and disposal activities at the TTR, and they are grouped together for site closure based on the similarity of the sites (waste disposal sites and trenches). The fifth CAS, CAS 03-19-001, is a hydrocarbon spill related to activities in the area. This site is grouped with this CAU because of the location (TTR). Based on historical documentation and process know-ledge, vertical and lateral migration routes are possible for all CASs. Migration of contaminants may have occurred through transport by infiltration of precipitation through surface soil which serves as a driving force for downward migration of contaminants. Land-use scenarios limit future use of these CASs to industrial activities. The suspected contaminants of potential concern which have been identified are volatile organic compounds; semivolatile organic compounds; high explosives; radiological constituents including depleted uranium, beryllium, total petroleum hydrocarbons; and total Resource Conservation and Recovery Act metals. Field activities will consist of geophysical and radiological surveys, and collecting soil samples at biased locations by appropriate methods. A two-step data quality objective strategy will be followed: (1) define the nature of contamination at each CAS location by identifying any contamination above preliminary action levels (PALs); and, (2) determine the extent of contamination identified above PALs. The results of this field investigation will support a defensible evaluation of corrective action alternatives in the corrective action decision document.« less

75 FR 39697 - Indians Into Psychology Program; Correction

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-12

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Indian Health Service Indians Into Psychology Program; Correction AGENCY: Indian Health Service, HHS. ACTION: Notice correction. SUMMARY: The Indian Health Service...-IHS-2010-INPSY-0001, for the Indians Into Psychology Program. The document contained an incorrect...

Phosphorothioate oligonucleotides inhibit the intrinsic tenase complex.

PubMed

Sheehan, J P; Lan, H C

1998-09-01

Systemic administration of ISIS 2302, a 20-mer antisense phosphorothioate oligonucleotide targeting human intercellular adhesion molecule-1 mRNA, causes prolongation of plasma clotting times in both monkey and human studies. The anticoagulant effects of ISIS 2302 were investigated with both in vitro coagulation assays in human plasma and purified enzyme systems. At high oligonucleotide plasma concentrations (>100 microgram/mL), prolongation of the prothrombin and thrombin times was observed. In a thrombin time assay using purified components, high concentrations of ISIS 2302 inhibited thrombin clotting activity both by stimulating inhibition by heparin cofactor II and directly competing with fibrinogen for binding to anion binding exosite I. In contrast, low concentrations of ISIS 2302 (<100 microgram/mL) showed a selective, linear prolongation of the activated partial thromboplastin time (PTT). The rate limiting effect of 50 microgram/mL ISIS 2302, which prolonged the PTT to 1.5 times control, was identified by sequential modification of the clotting assay. Delaying addition of oligonucleotide until after contact activation failed to correct prolongation of the PTT. The calcium-dependent steps of the intrinsic pathway were individually assessed by adding sufficient activated coagulation factor to correct the PTT in plasma deficient in that specific factor. Addition of factor XIa, IXa, VIIIa, or Va failed to correct the PTT in the presence of ISIS 2302. In contrast, 0.2 nmol/L factor Xa corrected prolongation of the PTT in factor X-deficient plasma with or without oligonucleotide present. ISIS 2302 (50 microgram/mL) did not prolong a modified Russel viper venom time, suggesting no significant inhibition of prothrombinase. Thus, 50 microgram/mL ISIS 2302 prolonged the PTT by selectively inhibiting intrinsic tenase activity. ISIS 2302 showed partial inhibition of intrinsic tenase activity (to approximately 35% of control) at clinically relevant oligonucleotide concentrations in a chromogenic assay. This activity was oligonucleotide sequence-independent but required the phosphorothioate backbone, suggesting that inhibition of intrinsic tenase is a general property of this class of oligonucleotides. These results are relevant to both the therapeutic use of phosphorothioate oligonucleotides and the potential design of inhibitors of the intrinsic tenase complex, a novel target for anticoagulation. Copyright 1998 by The American Society of Hematology.

An Allometric Analysis of Sex and Sex Chromosome Dosage Effects on Subcortical Anatomy in Humans.

PubMed

Reardon, Paul Kirkpatrick; Clasen, Liv; Giedd, Jay N; Blumenthal, Jonathan; Lerch, Jason P; Chakravarty, M Mallar; Raznahan, Armin

2016-02-24

Structural neuroimaging of humans with typical and atypical sex-chromosome complements has established the marked influence of both Yand X-/Y-chromosome dosage on total brain volume (TBV) and identified potential cortical substrates for the psychiatric phenotypes associated with sex-chromosome aneuploidy (SCA). Here, in a cohort of 354 humans with varying karyotypes (XX, XY, XXX, XXY, XYY, XXYY, XXXXY), we investigate sex and SCA effects on subcortical size and shape; focusing on the striatum, pallidum and thalamus. We find large effect-size differences in the volume and shape of all three structures as a function of sex and SCA. We correct for TBV effects with a novel allometric method harnessing normative scaling rules for subcortical size and shape in humans, which we derive here for the first time. We show that all three subcortical volumes scale sublinearly with TBV among healthy humans, mirroring known relationships between subcortical volume and TBV among species. Traditional TBV correction methods assume linear scaling and can therefore invert or exaggerate sex and SCA effects on subcortical anatomy. Allometric analysis restricts sex-differences to: (1) greater pallidal volume (PV) in males, and (2) relative caudate head expansion and ventral striatum contraction in females. Allometric analysis of SCA reveals that supernumerary X- and Y-chromosomes both cause disproportionate reductions in PV, and coordinated deformations of striatopallidal shape. Our study provides a novel understanding of sex and sex-chromosome dosage effects on subcortical organization, using an allometric approach that can be generalized to other basic and clinical structural neuroimaging settings. Copyright © 2016 the authors 0270-6474/16/362438-11$15.00/0.

A Prospective Treatment Option for Lysosomal Storage Diseases: CRISPR/Cas9 Gene Editing Technology for Mutation Correction in Induced Pluripotent Stem Cells

PubMed Central

Christensen, Chloe L.; Choy, Francis Y. M.

2017-01-01

Ease of design, relatively low cost and a multitude of gene-altering capabilities have all led to the adoption of the sophisticated and yet simple gene editing system: clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9). The CRISPR/Cas9 system holds promise for the correction of deleterious mutations by taking advantage of the homology directed repair pathway and by supplying a correction template to the affected patient’s cells. Currently, this technique is being applied in vitro in human-induced pluripotent stem cells (iPSCs) to correct a variety of severe genetic diseases, but has not as of yet been used in iPSCs derived from patients affected with a lysosomal storage disease (LSD). If adopted into clinical practice, corrected iPSCs derived from cells that originate from the patient themselves could be used for therapeutic amelioration of LSD symptoms without the risks associated with allogeneic stem cell transplantation. CRISPR/Cas9 editing in a patient’s cells would overcome the costly, lifelong process associated with currently available treatment methods, including enzyme replacement and substrate reduction therapies. In this review, the overall utility of the CRISPR/Cas9 gene editing technique for treatment of genetic diseases, the potential for the treatment of LSDs and methods currently employed to increase the efficiency of this re-engineered biological system will be discussed. PMID:28933359

Alpha phase determines successful lexical decision in noise.

PubMed

Strauß, Antje; Henry, Molly J; Scharinger, Mathias; Obleser, Jonas

2015-02-18

Psychophysical target detection has been shown to be modulated by slow oscillatory brain phase. However, thus far, only low-level sensory stimuli have been used as targets. The current human electroencephalography (EEG) study examined the influence of neural oscillatory phase on a lexical-decision task performed for stimuli embedded in noise. Neural phase angles were compared for correct versus incorrect lexical decisions using a phase bifurcation index (BI), which quantifies differences in mean phase angles and phase concentrations between correct and incorrect trials. Neural phase angles in the alpha frequency range (8-12 Hz) over right anterior sensors were approximately antiphase in a prestimulus time window, and thus successfully distinguished between correct and incorrect lexical decisions. Moreover, alpha-band oscillations were again approximately antiphase across participants for correct versus incorrect trials during a later peristimulus time window (∼500 ms) at left-central electrodes. Strikingly, lexical decision accuracy was not predicted by either event-related potentials (ERPs) or oscillatory power measures. We suggest that correct lexical decisions depend both on successful sensory processing, which is made possible by the alignment of stimulus onset with an optimal alpha phase, as well as integration and weighting of decisional information, which is coupled to alpha phase immediately following the critical manipulation that differentiated words from pseudowords. The current study constitutes a first step toward characterizing the role of dynamic oscillatory brain states for higher cognitive functions, such as spoken word recognition. Copyright © 2015 the authors 0270-6474/15/353256-07$15.00/0.

76 FR 50481 - Announcement of Requirements and Registration for “Lifeline Facebook App Challenge”; Correction

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-15

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Announcement of Requirements and Registration for ``Lifeline Facebook App Challenge''; Correction AGENCY: Office of the Assistant Secretary for Preparedness... Requirements and Registration for ``Lifeline Facebook App Challenge''. DATES: This correction is effective...

Resource Conservation and Recovery Act (RCRA) Corrective Action Training: Strategies for Meeting the 2020 Vision

EPA Pesticide Factsheets

RCRA Corrective Action training to develop and enhance the skills of qualified personnel who will implement corrective actions for their sites by the year 2020 that are protective of human health and the environment while encouraging revitalization.

77 FR 37421 - Reimbursement Rates for Calendar Year 2012 Correction

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-21

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Indian Health Service Reimbursement Rates for Calendar Year 2012 Correction AGENCY: Indian Health Service, HHS. ACTION: Notice; correction. SUMMARY: The Indian Health Service published a document in the Federal Register on June 6, 2012, concerning rates for...

Synchronizing movements with the metronome: nonlinear error correction and unstable periodic orbits.

PubMed

Engbert, Ralf; Krampe, Ralf Th; Kurths, Jürgen; Kliegl, Reinhold

2002-02-01

The control of human hand movements is investigated in a simple synchronization task. We propose and analyze a stochastic model based on nonlinear error correction; a mechanism which implies the existence of unstable periodic orbits. This prediction is tested in an experiment with human subjects. We find that our experimental data are in good agreement with numerical simulations of our theoretical model. These results suggest that feedback control of the human motor systems shows nonlinear behavior. Copyright 2001 Elsevier Science (USA).

[Review of influence of landing impact on human body (correction of boby) and its medical evaluation].

PubMed

Guo, Yao-yu; Tan, Cheng; Liu, Bing-kun; Jiang, Shi-zhong

2002-12-01

Landing impact is the dynamic factor that manned spaceship will inevitably meet after the mission has been completed, and impact force may cause damages to human tissues [correction of tissuses] and organs, even death. This paper described the characteristics of pathological and dynamic response of human body to landing impact, and discussed various related factors such as impact angle, fetters, design of cushion, harness and terrain condition. Medical evaluation of +Gx, +Gz, +/- Gy impacts were summarized.

[Septic arthritis caused by Streptococcus suis].

PubMed

Hedegaard, Sofie Sommer; Zaccarin, Matthias; Lindberg, Jens

2013-05-27

Streptococcus suis is a global endemic swine pathogen. S. suis can cause meningitis, endocarditis and severe sepsis in humans, who are exposed to swine. Human infection with S. suis was first reported in 1968, since then, human infections have been sporadic although an outbreak in China counted 215 cases. In a rare case of disseminated arthritis we found that correct clinical diagnosis was difficult due to unspecific symptomatology and slow growing bacterial culture. However, conducting thorough examinations is crucial, and if treated correctly the outcome is favourable.

Long-Term Correction of Sandhoff Disease Following Intravenous Delivery of rAAV9 to Mouse Neonates

PubMed Central

Walia, Jagdeep S; Altaleb, Naderah; Bello, Alexander; Kruck, Christa; LaFave, Matthew C; Varshney, Gaurav K; Burgess, Shawn M; Chowdhury, Biswajit; Hurlbut, David; Hemming, Richard; Kobinger, Gary P; Triggs-Raine, Barbara

2015-01-01

GM2 gangliosidoses are severe neurodegenerative disorders resulting from a deficiency in β-hexosaminidase A activity and lacking effective therapies. Using a Sandhoff disease (SD) mouse model (Hexb−/−) of the GM2 gangliosidoses, we tested the potential of systemically delivered adeno-associated virus 9 (AAV9) expressing Hexb cDNA to correct the neurological phenotype. Neonatal or adult SD and normal mice were intravenously injected with AAV9-HexB or –LacZ and monitored for serum β-hexosaminidase activity, motor function, and survival. Brain GM2 ganglioside, β-hexosaminidase activity, and inflammation were assessed at experimental week 43, or an earlier humane end point. SD mice injected with AAV9-LacZ died by 17 weeks of age, whereas all neonatal AAV9-HexB–treated SD mice survived until 43 weeks (P < 0.0001) with only three exhibiting neurological dysfunction. SD mice treated as adults with AAV9-HexB died between 17 and 35 weeks. Neonatal SD-HexB–treated mice had a significant increase in brain β-hexosaminidase activity, and a reduction in GM2 ganglioside storage and neuroinflammation compared to adult SD-HexB– and SD-LacZ–treated groups. However, at 43 weeks, 8 of 10 neonatal-HexB injected control and SD mice exhibited liver or lung tumors. This study demonstrates the potential for long-term correction of SD and other GM2 gangliosidoses through early rAAV9 based systemic gene therapy. PMID:25515709

Potential association of vacuum cleaning frequency with an altered gut microbiota in pregnant women and their 2-year-old children.

PubMed

Avershina, Ekaterina; Ravi, Anuradha; Storrø, Ola; Øien, Torbjørn; Johnsen, Roar; Rudi, Knut

2015-12-21

Westernized lifestyle and hygienic behavior have contributed to dramatic changes in the human-associated microbiota. This particularly relates to indoor activities such as house cleaning. We therefore investigated the associations between washing and vacuum cleaning frequency and the gut microbiota composition in a large longitudinal cohort of mothers and their children. The gut microbiota composition was determined using 16S ribosomal RNA (rRNA) gene Illumina deep sequencing. We found that high vacuum cleaning frequency about twice or more a week was associated with an altered gut microbiota composition both during pregnancy and for 2-year-old children, while there were no associations with house washing frequency. In total, six Operational Taxonomic Units (OTUs) showed significant False Discovery Rate (FDR) corrected associations with vacuum cleaning frequency for mothers (two positive and four negative) and five for 2-year-old children (four positive and one negative). For mothers and the 2-year-old children, OTUs among the dominant microbiota (average >5 %) showed correlation to vacuum cleaning frequency, with an increase in Faecalibacterium prausnitzii for mothers (p = 0.013, FDR corrected), and Blautia sp. for 2-year children (p = 0.012, FDR corrected). Bacteria showing significant associations are among the dominant gut microbiota, which may indicate indirect immunomodulation of the gut microbiota possibly through increased allergen (dust mites) exposure as a potential mechanism. However, further exploration is needed to unveil mechanistic details.

Ab Initio and Analytic Intermolecular Potentials for Ar-CF₄

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

Vayner, Grigoriy; Alexeev, Yuri; Wang, Jiangping

2006-03-09

Ab initio calculations at the CCSD(T) level of theory are performed to characterize the Ar + CF ₄ intermolecular potential. Extensive calculations, with and without a correction for basis set superposition error (BSSE), are performed with the cc-pVTZ basis set. Additional calculations are performed with other correlation consistent (cc) basis sets to extrapolate the Ar---CF₄potential energy minimum to the complete basis set (CBS) limit. Both the size of the basis set and BSSE have substantial effects on the Ar + CF₄ potential. Calculations with the cc-pVTZ basis set and without a BSSE correction, appear to give a good representation ofmore » the potential at the CBS limit and with a BSSE correction. In addition, MP2 theory is found to give potential energies in very good agreement with those determined by the much higher level CCSD(T) theory. Two analytic potential energy functions were determined for Ar + CF₄by fitting the cc-pVTZ calculations both with and without a BSSE correction. These analytic functions were written as a sum of two body potentials and excellent fits to the ab initio potentials were obtained by representing each two body interaction as a Buckingham potential.« less

Availability of human induced pluripotent stem cell-derived cardiomyocytes in assessment of drug potential for QT prolongation

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

Nozaki, Yumiko, E-mail: yumiko-nozaki@ds-pharma.co.jp; Honda, Yayoi, E-mail: yayoi-honda@ds-pharma.co.jp; Tsujimoto, Shinji, E-mail: shinji-tsujimoto@ds-pharma.co.jp

2014-07-01

Field potential duration (FPD) in human-induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs), which can express QT interval in an electrocardiogram, is reported to be a useful tool to predict K{sup +} channel and Ca{sup 2+} channel blocker effects on QT interval. However, there is no report showing that this technique can be used to predict multichannel blocker potential for QT prolongation. The aim of this study is to show that FPD from MEA (Multielectrode array) of hiPS-CMs can detect QT prolongation induced by multichannel blockers. hiPS-CMs were seeded onto MEA and FPD was measured for 2 min every 10 min formore » 30 min after drug exposure for the vehicle and each drug concentration. I{sub Kr} and I{sub Ks} blockers concentration-dependently prolonged corrected FPD (FPDc), whereas Ca{sup 2+} channel blockers concentration-dependently shortened FPDc. Also, the multichannel blockers Amiodarone, Paroxetine, Terfenadine and Citalopram prolonged FPDc in a concentration dependent manner. Finally, the I{sub Kr} blockers, Terfenadine and Citalopram, which are reported to cause Torsade de Pointes (TdP) in clinical practice, produced early afterdepolarization (EAD). hiPS-CMs using MEA system and FPDc can predict the effects of drug candidates on QT interval. This study also shows that this assay can help detect EAD for drugs with TdP potential. - Highlights: • We focused on hiPS-CMs to replace in vitro assays in preclinical screening studies. • hiPS-CMs FPD is useful as an indicator to predict drug potential for QT prolongation. • MEA assay can help detect EAD for drugs with TdP potentials. • MEA assay in hiPS-CMs is useful for accurately predicting drug TdP risk in humans.« less

First-in-Human Assessment of the Novel PDE2A PET Radiotracer 18F-PF-05270430

PubMed Central

Waterhouse, Rikki N.; Nabulsi, Nabeel; Lin, Shu-Fei; Labaree, David; Ropchan, Jim; Tarabar, Sanela; DeMartinis, Nicholas; Ogden, Adam; Banerjee, Anindita; Huang, Yiyun; Carson, Richard E.

2016-01-01

This was a first-in-human study of the novel phosphodiesterase-2A (PDE2A) PET ligand 18F-PF-05270430. The primary goals were to determine the appropriate tracer kinetic model to quantify brain uptake and to examine the within-subject test–retest variability. Methods: In advance of human studies, radiation dosimetry was determined in nonhuman primates. Six healthy male subjects participated in a test–retest protocol with dynamic scans and metabolite-corrected input functions. Nine brain regions of interest were studied, including the striatum, white matter, neocortical regions, and cerebellum. Multiple modeling methods were applied to calculate volume of distribution (VT) and binding potentials relative to the nondisplaceable tracer in tissue (BPND), concentration of tracer in plasma (BPP), and free tracer in tissue (BPF). The cerebellum was selected as a reference region to calculate binding potentials. Results: The dosimetry study provided an effective dose of less than 0.30 mSv/MBq, with the gallbladder as the critical organ; the human target dose was 185 MBq. There were no adverse events or clinically detectable pharmacologic effects reported. Tracer uptake was highest in the striatum, followed by neocortical regions and white matter, and lowest in the cerebellum. Regional time–activity curves were well fit by multilinear analysis-1, and a 70-min scan duration was sufficient to quantify VT and the binding potentials. BPND, with mean values ranging from 0.3 to 0.8, showed the best intrasubject and intersubject variability and reliability. Test–retest variability in the whole brain (excluding the cerebellum) of VT, BPND, and BPP were 8%, 16%, and 17%, respectively. Conclusion: 18F-PF-05270430 shows promise as a PDE2A PET ligand, albeit with low binding potential values. PMID:27103022

Pred-Skin: A Fast and Reliable Web Application to Assess Skin Sensitization Effect of Chemicals.

PubMed

Braga, Rodolpho C; Alves, Vinicius M; Muratov, Eugene N; Strickland, Judy; Kleinstreuer, Nicole; Trospsha, Alexander; Andrade, Carolina Horta

2017-05-22

Chemically induced skin sensitization is a complex immunological disease with a profound impact on quality of life and working ability. Despite some progress in developing alternative methods for assessing the skin sensitization potential of chemical substances, there is no in vitro test that correlates well with human data. Computational QSAR models provide a rapid screening approach and contribute valuable information for the assessment of chemical toxicity. We describe the development of a freely accessible web-based and mobile application for the identification of potential skin sensitizers. The application is based on previously developed binary QSAR models of skin sensitization potential from human (109 compounds) and murine local lymph node assay (LLNA, 515 compounds) data with good external correct classification rate (0.70-0.81 and 0.72-0.84, respectively). We also included a multiclass skin sensitization potency model based on LLNA data (accuracy ranging between 0.73 and 0.76). When a user evaluates a compound in the web app, the outputs are (i) binary predictions of human and murine skin sensitization potential; (ii) multiclass prediction of murine skin sensitization; and (iii) probability maps illustrating the predicted contribution of chemical fragments. The app is the first tool available that incorporates quantitative structure-activity relationship (QSAR) models based on human data as well as multiclass models for LLNA. The Pred-Skin web app version 1.0 is freely available for the web, iOS, and Android (in development) at the LabMol web portal ( http://labmol.com.br/predskin/ ), in the Apple Store, and on Google Play, respectively. We will continuously update the app as new skin sensitization data and respective models become available.

Iteration of ultrasound aberration correction methods

NASA Astrophysics Data System (ADS)

Maasoey, Svein-Erik; Angelsen, Bjoern; Varslot, Trond

2004-05-01

Aberration in ultrasound medical imaging is usually modeled by time-delay and amplitude variations concentrated on the transmitting/receiving array. This filter process is here denoted a TDA filter. The TDA filter is an approximation to the physical aberration process, which occurs over an extended part of the human body wall. Estimation of the TDA filter, and performing correction on transmit and receive, has proven difficult. It has yet to be shown that this method works adequately for severe aberration. Estimation of the TDA filter can be iterated by retransmitting a corrected signal and re-estimate until a convergence criterion is fulfilled (adaptive imaging). Two methods for estimating time-delay and amplitude variations in receive signals from random scatterers have been developed. One method correlates each element signal with a reference signal. The other method use eigenvalue decomposition of the receive cross-spectrum matrix, based upon a receive energy-maximizing criterion. Simulations of iterating aberration correction with a TDA filter have been investigated to study its convergence properties. A weak and strong human-body wall model generated aberration. Both emulated the human abdominal wall. Results after iteration improve aberration correction substantially, and both estimation methods converge, even for the case of strong aberration.

Three-dimensional ray tracing for refractive correction of human eye ametropies

NASA Astrophysics Data System (ADS)

Jimenez-Hernandez, J. A.; Diaz-Gonzalez, G.; Trujillo-Romero, F.; Iturbe-Castillo, M. D.; Juarez-Salazar, R.; Santiago-Alvarado, A.

2016-09-01

Ametropies of the human eye, are refractive defects hampering the correct imaging on the retina. The most common ways to correct them is by means of spectacles, contact lenses, and modern methods as laser surgery. However, in any case it is very important to identify the ametropia grade for designing the optimum correction action. In the case of laser surgery, it is necessary to define a new shape of the cornea in order to obtain the wanted refractive correction. Therefore, a computational tool to calculate the focal length of the optical system of the eye versus variations on its geometrical parameters is required. Additionally, a clear and understandable visualization of the evaluation process is desirable. In this work, a model of the human eye based on geometrical optics principles is presented. Simulations of light rays coming from a punctual source at six meter from the cornea are shown. We perform a ray-tracing in three dimensions in order to visualize the focusing regions and estimate the power of the optical system. The common parameters of ametropies can be easily modified and analyzed in the simulation by an intuitive graphic user interface.

MRI-assisted PET motion correction for neurologic studies in an integrated MR-PET scanner.

PubMed

Catana, Ciprian; Benner, Thomas; van der Kouwe, Andre; Byars, Larry; Hamm, Michael; Chonde, Daniel B; Michel, Christian J; El Fakhri, Georges; Schmand, Matthias; Sorensen, A Gregory

2011-01-01

Head motion is difficult to avoid in long PET studies, degrading the image quality and offsetting the benefit of using a high-resolution scanner. As a potential solution in an integrated MR-PET scanner, the simultaneously acquired MRI data can be used for motion tracking. In this work, a novel algorithm for data processing and rigid-body motion correction (MC) for the MRI-compatible BrainPET prototype scanner is described, and proof-of-principle phantom and human studies are presented. To account for motion, the PET prompt and random coincidences and sensitivity data for postnormalization were processed in the line-of-response (LOR) space according to the MRI-derived motion estimates. The processing time on the standard BrainPET workstation is approximately 16 s for each motion estimate. After rebinning in the sinogram space, the motion corrected data were summed, and the PET volume was reconstructed using the attenuation and scatter sinograms in the reference position. The accuracy of the MC algorithm was first tested using a Hoffman phantom. Next, human volunteer studies were performed, and motion estimates were obtained using 2 high-temporal-resolution MRI-based motion-tracking techniques. After accounting for the misalignment between the 2 scanners, perfectly coregistered MRI and PET volumes were reproducibly obtained. The MRI output gates inserted into the PET list-mode allow the temporal correlation of the 2 datasets within 0.2 ms. The Hoffman phantom volume reconstructed by processing the PET data in the LOR space was similar to the one obtained by processing the data using the standard methods and applying the MC in the image space, demonstrating the quantitative accuracy of the procedure. In human volunteer studies, motion estimates were obtained from echo planar imaging and cloverleaf navigator sequences every 3 s and 20 ms, respectively. Motion-deblurred PET images, with excellent delineation of specific brain structures, were obtained using these 2 MRI-based estimates. An MRI-based MC algorithm was implemented for an integrated MR-PET scanner. High-temporal-resolution MRI-derived motion estimates (obtained while simultaneously acquiring anatomic or functional MRI data) can be used for PET MC. An MRI-based MC method has the potential to improve PET image quality, increasing its reliability, reproducibility, and quantitative accuracy, and to benefit many neurologic applications.

Intestinal parasites of owned dogs and cats from metropolitan and micropolitan areas: prevalence, zoonotic risks, and pet owner awareness in northern Italy.

PubMed

Zanzani, Sergio Aurelio; Gazzonis, Alessia Libera; Scarpa, Paola; Berrilli, Federica; Manfredi, Maria Teresa

2014-01-01

Intestinal parasites of dogs and cats are cosmopolitan pathogens with zoonotic potential for humans. Our investigation considered their diffusion in dogs and cats from northern Italy areas, specifically the metropolitan area of Milan and two micropolitan areas of neighboring provinces. It included the study of the level of awareness in pet owners of the zoonotic potential from these parasites. A total of 409 fresh fecal samples were collected from household dogs and cats for copromicroscopic analysis and detection of Giardia duodenalis coproantigens. The assemblages of Giardia were also identified. A questionnaire about intestinal parasites biology and zoonotic potential was submitted to 185 pet owners. The overall prevalence of intestinal parasites resulted higher in cats (47.37%-60.42%) and dogs (57.41%-43.02%) from micropolitan areas than that from the metropolis of Milan (dogs: P = 28.16%; cats: P = 32.58 %). The zoonotic parasites infecting pets under investigation were T. canis and T. cati, T. vulpis, Ancylostomatidae, and G. duodenalis assemblage A. Only 49.19% of pet owners showed to be aware of the risks for human health from canine and feline intestinal parasites. Parasitological results in pets and awareness determination in their owners clearly highlight how the role of veterinarians is important in indicating correct and widespread behaviors to reduce risks of infection for pets and humans in urban areas.

Cognitive caching promotes flexibility in task switching: evidence from event-related potentials.

PubMed

Lange, Florian; Seer, Caroline; Müller, Dorothea; Kopp, Bruno

2015-12-08

Time-consuming processes of task-set reconfiguration have been shown to contribute to the costs of switching between cognitive tasks. We describe and probe a novel mechanism serving to reduce the costs of task-set reconfiguration. We propose that when individuals are uncertain about the currently valid task, one task set is activated for execution while other task sets are maintained at a pre-active state in cognitive cache. We tested this idea by assessing an event-related potential (ERP) index of task-set reconfiguration in a three-rule task-switching paradigm involving varying degrees of task uncertainty. In high-uncertainty conditions, two viable tasks were equally likely to be correct whereas in low-uncertainty conditions, one task was more likely than the other. ERP and performance measures indicated substantial costs of task-set reconfiguration when participants were required to switch away from a task that had been likely to be correct. In contrast, task-set-reconfiguration costs were markedly reduced when the previous task set was chosen under high task uncertainty. These results suggest that cognitive caching of alternative task sets adds to human cognitive flexibility under high task uncertainty.

Cognitive caching promotes flexibility in task switching: evidence from event-related potentials

PubMed Central

Lange, Florian; Seer, Caroline; Müller, Dorothea; Kopp, Bruno

2015-01-01

Time-consuming processes of task-set reconfiguration have been shown to contribute to the costs of switching between cognitive tasks. We describe and probe a novel mechanism serving to reduce the costs of task-set reconfiguration. We propose that when individuals are uncertain about the currently valid task, one task set is activated for execution while other task sets are maintained at a pre-active state in cognitive cache. We tested this idea by assessing an event-related potential (ERP) index of task-set reconfiguration in a three-rule task-switching paradigm involving varying degrees of task uncertainty. In high-uncertainty conditions, two viable tasks were equally likely to be correct whereas in low-uncertainty conditions, one task was more likely than the other. ERP and performance measures indicated substantial costs of task-set reconfiguration when participants were required to switch away from a task that had been likely to be correct. In contrast, task-set-reconfiguration costs were markedly reduced when the previous task set was chosen under high task uncertainty. These results suggest that cognitive caching of alternative task sets adds to human cognitive flexibility under high task uncertainty. PMID:26643146

The influence of the atmosphere on geoid and potential coefficient determinations from gravity data

NASA Technical Reports Server (NTRS)

Rummel, R.; Rapp, R. H.

1976-01-01

For the precise computation of geoid undulations the effect of the attraction of the atmosphere on the solution of the basic boundary value problem of gravimetric geodesy must be considered. This paper extends the theory of Moritz for deriving an atmospheric correction to the case when the undulations are computed by combining anomalies in a cap surrounding the computation point with information derived from potential coefficients. The correction term is a function of the cap size and the topography within the cap. It reaches a value of 3.0 m for a cap size of 30 deg, variations on the decimeter level being caused by variations in the topography. The effect of the atmospheric correction terms on potential coefficients is found to be small, reaching a maximum of 0.0055 millionths at n = 2, m = 2 when terrestrial gravity data are considered. The magnitude of this correction indicates that in future potential coefficient determination from gravity data the atmospheric correction should be made to such data.

77 FR 1941 - Statement of Organization, Functions, and Delegations of Authority; Correction

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-12

... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health Statement of Organization, Functions, and Delegations of Authority; Correction Correction In the Federal Register of January 6, 2012... of Health Statement of Organization, Functions, and Delegations of Authority. On page 797, in the...

76 FR 3908 - Office for State, Tribal, Local and Territorial Support (OSTLTS); Correction

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... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention Office for State, Tribal, Local and Territorial Support (OSTLTS); Correction Correction: This notice was published... place should read as follows: Office for State, Tribal, Local and Territorial Support (OSTLTS) Place...

The Human Subsystem - Definition and Integration

NASA Technical Reports Server (NTRS)

vonBengston, Kristian; Twyford, Evan

2007-01-01

This paper will discuss the use of the human subsystem in development phases of human space flight. Any space mission has clearly defined subsystems, managed by experts attached to these. Clearly defined subsystems and correct use provide easier and more efficient development for each independent subsystem and for the relation between these subsystems. Furthermore, this paper will argue that a defined subsystem related to humans in space has not always been clearly present, and that correct implementation is perhaps missing, based on experience and survey data. Finally, the authors will discuss why the human subsystem has not been fully integrated, why it must be a mandatory part of the programming, a re-definition of the human subsystem, and suggestions of methods to improve the integration of human factors in the development.

A Novel Spinal Implant for Fusionless Scoliosis Correction: A Biomechanical Analysis of the Motion Preserving Properties of a Posterior Periapical Concave Distraction Device.

PubMed

Holewijn, Roderick M; de Kleuver, Marinus; van der Veen, Albert J; Emanuel, Kaj S; Bisschop, Arno; Stadhouder, Agnita; van Royen, Barend J; Kingma, Idsart

2017-08-01

Biomechanical study. Recently, a posterior concave periapical distraction device for fusionless scoliosis correction was introduced. The goal of this study was to quantify the effect of the periapical distraction device on spinal range of motion (ROM) in comparison with traditional rigid pedicle screw-rod instrumentation. Using a spinal motion simulator, 6 human spines were loaded with 4 N m and 6 porcine spines with 2 N m to induce flexion-extension (FE), lateral bending (LB), and axial rotation (AR). ROM was measured in 3 conditions: untreated, periapical distraction device, and rigid pedicle screw-rod instrumentation. The periapical distraction device caused a significant ( P < .05) decrease in ROM of FE (human, -40.0% and porcine, -55.9%) and LB (human, -18.2% and porcine, -17.9%) as compared to the untreated spine, while ROM of AR remained unaffected. In comparison, rigid instrumentation caused a significantly ( P < .05) larger decrease in ROM of FE (human, -80.9% and porcine, -94.0%), LB (human, -75.0% and porcine, -92.2%), and AR (human, -71.3% and porcine, -86.9%). Although no destructive forces were applied, no device failures were observed. Spinal ROM was significantly less constrained by the periapical distraction device compared to rigid pedicle screw-rod instrumentation. Therefore, provided that scoliosis correction is achieved, a more physiological spinal motion is expected after scoliosis correction with the posterior concave periapical distraction device.

A Molecular Sensor To Characterize Arenavirus Envelope Glycoprotein Cleavage by Subtilisin Kexin Isozyme 1/Site 1 Protease.

PubMed

Oppliger, Joel; da Palma, Joel Ramos; Burri, Dominique J; Bergeron, Eric; Khatib, Abdel-Majid; Spiropoulou, Christina F; Pasquato, Antonella; Kunz, Stefan

2016-01-15

Arenaviruses are emerging viruses including several causative agents of severe hemorrhagic fevers in humans. The advent of next-generation sequencing technology has greatly accelerated the discovery of novel arenavirus species. However, for many of these viruses, only genetic information is available, and their zoonotic disease potential remains unknown. During the arenavirus life cycle, processing of the viral envelope glycoprotein precursor (GPC) by the cellular subtilisin kexin isozyme 1 (SKI-1)/site 1 protease (S1P) is crucial for productive infection. The ability of newly emerging arenaviruses to hijack human SKI-1/S1P appears, therefore, to be a requirement for efficient zoonotic transmission and human disease potential. Here we implement a newly developed cell-based molecular sensor for SKI-1/S1P to characterize the processing of arenavirus GPC-derived target sequences by human SKI-1/S1P in a quantitative manner. We show that only nine amino acids flanking the putative cleavage site are necessary and sufficient to accurately recapitulate the efficiency and subcellular location of arenavirus GPC processing. In a proof of concept, our sensor correctly predicts efficient processing of the GPC of the newly emergent pathogenic Lujo virus by human SKI-1/S1P and defines the exact cleavage site. Lastly, we employed our sensor to show efficient GPC processing of a panel of pathogenic and nonpathogenic New World arenaviruses, suggesting that GPC cleavage represents no barrier for zoonotic transmission of these pathogens. Our SKI-1/S1P sensor thus represents a rapid and robust test system for assessment of the processing of putative cleavage sites derived from the GPCs of newly discovered arenavirus by the SKI-1/S1P of humans or any other species, based solely on sequence information. Arenaviruses are important emerging human pathogens that can cause severe hemorrhagic fevers with high mortality in humans. A crucial step in productive arenavirus infection of human cells is the processing of the viral envelope glycoprotein by the cellular subtilisin kexin isozyme 1 (SKI-1)/site 1 protease (S1P). In order to break the species barrier during zoonotic transmission and cause severe disease in humans, newly emerging arenaviruses must be able to hijack human SKI-1/S1P efficiently. Here we implement a newly developed cell-based molecular sensor for human SKI-1/S1P to characterize the processing of arenavirus glycoproteins in a quantitative manner. We further use our sensor to correctly predict efficient processing of the glycoprotein of the newly emergent pathogenic Lujo virus by human SKI-1/S1P. Our sensor thus represents a rapid and robust test system with which to assess whether the glycoprotein of any newly emerging arenavirus can be efficiently processed by human SKI-1/S1P, based solely on sequence information. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

An advanced method to assess the diet of free-ranging large carnivores based on scats.

PubMed

Wachter, Bettina; Blanc, Anne-Sophie; Melzheimer, Jörg; Höner, Oliver P; Jago, Mark; Hofer, Heribert

2012-01-01

The diet of free-ranging carnivores is an important part of their ecology. It is often determined from prey remains in scats. In many cases, scat analyses are the most efficient method but they require correction for potential biases. When the diet is expressed as proportions of consumed mass of each prey species, the consumed prey mass to excrete one scat needs to be determined and corrected for prey body mass because the proportion of digestible to indigestible matter increases with prey body mass. Prey body mass can be corrected for by conducting feeding experiments using prey of various body masses and fitting a regression between consumed prey mass to excrete one scat and prey body mass (correction factor 1). When the diet is expressed as proportions of consumed individuals of each prey species and includes prey animals not completely consumed, the actual mass of each prey consumed by the carnivore needs to be controlled for (correction factor 2). No previous study controlled for this second bias. Here we use an extended series of feeding experiments on a large carnivore, the cheetah (Acinonyx jubatus), to establish both correction factors. In contrast to previous studies which fitted a linear regression for correction factor 1, we fitted a biologically more meaningful exponential regression model where the consumed prey mass to excrete one scat reaches an asymptote at large prey sizes. Using our protocol, we also derive correction factor 1 and 2 for other carnivore species and apply them to published studies. We show that the new method increases the number and proportion of consumed individuals in the diet for large prey animals compared to the conventional method. Our results have important implications for the interpretation of scat-based studies in feeding ecology and the resolution of human-wildlife conflicts for the conservation of large carnivores.

An Advanced Method to Assess the Diet of Free-Ranging Large Carnivores Based on Scats

PubMed Central

Wachter, Bettina; Blanc, Anne-Sophie; Melzheimer, Jörg; Höner, Oliver P.; Jago, Mark; Hofer, Heribert

2012-01-01

Background The diet of free-ranging carnivores is an important part of their ecology. It is often determined from prey remains in scats. In many cases, scat analyses are the most efficient method but they require correction for potential biases. When the diet is expressed as proportions of consumed mass of each prey species, the consumed prey mass to excrete one scat needs to be determined and corrected for prey body mass because the proportion of digestible to indigestible matter increases with prey body mass. Prey body mass can be corrected for by conducting feeding experiments using prey of various body masses and fitting a regression between consumed prey mass to excrete one scat and prey body mass (correction factor 1). When the diet is expressed as proportions of consumed individuals of each prey species and includes prey animals not completely consumed, the actual mass of each prey consumed by the carnivore needs to be controlled for (correction factor 2). No previous study controlled for this second bias. Methodology/Principal Findings Here we use an extended series of feeding experiments on a large carnivore, the cheetah (Acinonyx jubatus), to establish both correction factors. In contrast to previous studies which fitted a linear regression for correction factor 1, we fitted a biologically more meaningful exponential regression model where the consumed prey mass to excrete one scat reaches an asymptote at large prey sizes. Using our protocol, we also derive correction factor 1 and 2 for other carnivore species and apply them to published studies. We show that the new method increases the number and proportion of consumed individuals in the diet for large prey animals compared to the conventional method. Conclusion/Significance Our results have important implications for the interpretation of scat-based studies in feeding ecology and the resolution of human-wildlife conflicts for the conservation of large carnivores. PMID:22715373

78 FR 64007 - Notice of Inventory Completion: University of Denver Department of Anthropology and Museum of...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-25

....R50000] Notice of Inventory Completion: University of Denver Department of Anthropology and Museum of Anthropology, Denver, CO; Correction AGENCY: National Park Service, Interior. ACTION: Notice; correction. SUMMARY: The University of Denver Museum of Anthropology has corrected an inventory of human remains and...

78 FR 63223 - Fibromyalgia Public Meeting on Patient-Focused Drug Development; Correction

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-23

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-N-2013-1041] Fibromyalgia Public Meeting on Patient-Focused Drug Development; Correction AGENCY: Food and Drug Administration, HHS. ACTION: Notice of public meeting; request for comments; correction. SUMMARY: The Food and...

40 CFR 264.101 - Corrective action for solid waste management units.

Code of Federal Regulations, 2013 CFR

2013-07-01

..., storage or disposal of hazardous waste must institute corrective action as necessary to protect human... 40 Protection of Environment 27 2013-07-01 2013-07-01 false Corrective action for solid waste... (CONTINUED) SOLID WASTES (CONTINUED) STANDARDS FOR OWNERS AND OPERATORS OF HAZARDOUS WASTE TREATMENT, STORAGE...

40 CFR 264.101 - Corrective action for solid waste management units.

Code of Federal Regulations, 2014 CFR

2014-07-01

..., storage or disposal of hazardous waste must institute corrective action as necessary to protect human... 40 Protection of Environment 26 2014-07-01 2014-07-01 false Corrective action for solid waste... (CONTINUED) SOLID WASTES (CONTINUED) STANDARDS FOR OWNERS AND OPERATORS OF HAZARDOUS WASTE TREATMENT, STORAGE...

40 CFR 264.101 - Corrective action for solid waste management units.

Code of Federal Regulations, 2012 CFR

2012-07-01

..., storage or disposal of hazardous waste must institute corrective action as necessary to protect human... 40 Protection of Environment 27 2012-07-01 2012-07-01 false Corrective action for solid waste... (CONTINUED) SOLID WASTES (CONTINUED) STANDARDS FOR OWNERS AND OPERATORS OF HAZARDOUS WASTE TREATMENT, STORAGE...

78 FR 39649 - Physical Medicine Devices; Reclassification of Stair-Climbing Wheelchairs; Correction

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-02

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 890 [Docket No. FDA-2013-N-0568] Physical Medicine Devices; Reclassification of Stair-Climbing Wheelchairs; Correction AGENCY: Food and Drug Administration, HHS. ACTION: Proposed order; correction. SUMMARY: The Food and Drug...

77 FR 36563 - Indian Health Service; Reimbursement Rates for Calendar Year 2012 Correction

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-19

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Indian Health Service; Reimbursement Rates for Calendar Year 2012 Correction AGENCY: Indian Health Service, HHS. ACTION: Notice; correction. SUMMARY: The Indian Health Service published a document in the Federal Register on June 6, 2012, concerning rates for...

77 FR 30887 - Amendments to Sterility Test Requirements for Biological Products; Correction

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-24

... Biological Products; Correction AGENCY: Food and Drug Administration, HHS. ACTION: Final rule, correction... Evaluation and Research (HFM-17), Food and Drug Administration, 1401 Rockville Pike, Suite 200N, Rockville... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Parts 600, 610, and...

Anatomic Pathways of Peripancreatic Fluid Draining to Mediastinum in Recurrent Acute Pancreatitis: Visible Human Project and CT Study

PubMed Central

Xu, Haotong; Zhang, Xiaoming; Christe, Andreas; Ebner, Lukas; Zhang, Shaoxiang; Luo, Zhulin; Wu, Yi; Li, Yin; Tian, Fuzhou

2013-01-01

Background In past reports, researchers have seldom attached importance to achievements in transforming digital anatomy to radiological diagnosis. However, investigators have been able to illustrate communication relationships in the retroperitoneal space by drawing potential routes in computerized tomography (CT) images or a virtual anatomical atlas. We established a new imaging anatomy research method for comparisons of the communication relationships of the retroperitoneal space in combination with the Visible Human Project and CT images. Specifically, the anatomic pathways of peripancreatic fluid extension to the mediastinum that may potentially transform into fistulas were studied. Methods We explored potential pathways to the mediastinum based on American and Chinese Visible Human Project datasets. These drainage pathways to the mediastinum were confirmed or corrected in CT images of 51 patients with recurrent acute pancreatitis in 2011. We also investigated whether additional routes to the mediastinum were displayed in CT images that were not in Visible Human Project images. Principal Findings All hypothesized routes to the mediastinum displayed in Visible Human Project images, except for routes from the retromesenteric plane to the bilateral retrorenal plane across the bilateral fascial trifurcation and further to the retrocrural space via the aortic hiatus, were confirmed in CT images. In addition, route 13 via the narrow space between the left costal and crural diaphragm into the retrocrural space was demonstrated for the first time in CT images. Conclusion This type of exploration model related to imaging anatomy may be used to support research on the communication relationships of abdominal spaces, mediastinal spaces, cervical fascial spaces and other areas of the body. PMID:23614005

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

Olivier, C. P., E-mail: colivier@sansa.org.za; Maharaj, S. K., E-mail: smaharaj@sansa.org.za, E-mail: rbharuthram@uwc.ac.za; Bharuthram, R., E-mail: rbharuthram@uwc.ac.za

In a series of papers by Maharaj et al., including “Existence domains of slow and fast ion-acoustic solitons in two-ion space plasmas” [Phys. Plasmas 22, 032313 (2015)], incorrect expressions for the Sagdeev potential are presented. In this paper, we provide the correct expression of the Sagdeev potential. The correct expression was used to generate the numerical results for the above-mentioned series of papers, so that all results and conclusions are correct, despite the wrong Sagdeev potential expressions printed in the papers. The correct expression of the Sagdeev potential presented here is a very useful generic expression in the sense thatmore » a single expression can be used to study nonlinear structures associated with any acoustic mode, despite the fact that the supersonic and subsonic species would vary if solitons associated with different linear modes are studied.« less

Machine vs. human translation of SNOMED CT terms.

PubMed

Schulz, Stefan; Bernhardt-Melischnig, Johannes; Kreuzthaler, Markus; Daumke, Philipp; Boeker, Martin

2013-01-01

In the context of past and current SNOMED CT translation projects we compare three kinds of SNOMED CT translations from English to German by: (t1) professional medical translators; (t2) a free Web-based machine translation service; (t3) medical students. 500 SNOMED CT fully specified names from the (English) International release were randomly selected. Based on this, German translations t1, t2, and t3 were generated. A German and an Austrian physician rated the translations for linguistic correctness and content fidelity. Kappa for inter-rater reliability was 0.4 for linguistic correctness and 0.23 for content fidelity. Average ratings of linguistic correctness did not differ significantly between human translation scenarios. Content fidelity was rated slightly better for student translators compared to professional translators. Comparing machine to human translation, the linguistic correctness differed about 0.5 scale units in favour of the human translation and about 0.25 regarding content fidelity, equally in favour of the human translation. The results demonstrate that low-cost translation solutions of medical terms may produce surprisingly good results. Although we would not recommend low-cost translation for producing standardized preferred terms, this approach can be useful for creating additional language-specific entry terms. This may serve several important use cases. We also recommend testing this method to bootstrap a crowdsourcing process, by which term translations are gathered, improved, maintained, and rated by the user community.

Motion correction of PET brain images through deconvolution: II. Practical implementation and algorithm optimization

NASA Astrophysics Data System (ADS)

Raghunath, N.; Faber, T. L.; Suryanarayanan, S.; Votaw, J. R.

2009-02-01

Image quality is significantly degraded even by small amounts of patient motion in very high-resolution PET scanners. When patient motion is known, deconvolution methods can be used to correct the reconstructed image and reduce motion blur. This paper describes the implementation and optimization of an iterative deconvolution method that uses an ordered subset approach to make it practical and clinically viable. We performed ten separate FDG PET scans using the Hoffman brain phantom and simultaneously measured its motion using the Polaris Vicra tracking system (Northern Digital Inc., Ontario, Canada). The feasibility and effectiveness of the technique was studied by performing scans with different motion and deconvolution parameters. Deconvolution resulted in visually better images and significant improvement as quantified by the Universal Quality Index (UQI) and contrast measures. Finally, the technique was applied to human studies to demonstrate marked improvement. Thus, the deconvolution technique presented here appears promising as a valid alternative to existing motion correction methods for PET. It has the potential for deblurring an image from any modality if the causative motion is known and its effect can be represented in a system matrix.

Evaluation of simulation-based scatter correction for 3-D PET cardiac imaging

NASA Astrophysics Data System (ADS)

Watson, C. C.; Newport, D.; Casey, M. E.; deKemp, R. A.; Beanlands, R. S.; Schmand, M.

1997-02-01

Quantitative imaging of the human thorax poses one of the most difficult challenges for three-dimensional (3-D) (septaless) positron emission tomography (PET), due to the strong attenuation of the annihilation radiation and the large contribution of scattered photons to the data. In [/sup 18/F] fluorodeoxyglucose (FDG) studies of the heart with the patient's arms in the field of view, the contribution of scattered events can exceed 50% of the total detected coincidences. Accurate correction for this scatter component is necessary for meaningful quantitative image analysis and tracer kinetic modeling. For this reason, the authors have implemented a single-scatter simulation technique for scatter correction in positron volume imaging. Here, they describe this algorithm and present scatter correction results from human and chest phantom studies.

To Nick or Not to Nick: Comparison of I-SceI Single- and Double-Strand Break-Induced Recombination in Yeast and Human Cells

PubMed Central

Katz, Samantha S.; Gimble, Frederick S.; Storici, Francesca

2014-01-01

Genetic modification of a chromosomal locus to replace an existing dysfunctional allele with a corrected sequence can be accomplished through targeted gene correction using the cell's homologous recombination (HR) machinery. Gene targeting is stimulated by generation of a DNA double-strand break (DSB) at or near the site of correction, but repair of the break via non-homologous end-joining without using the homologous template can lead to deleterious genomic changes such as in/del mutations, or chromosomal rearrangements. By contrast, generation of a DNA single-strand break (SSB), or nick, can stimulate gene correction without the problems of DSB repair because the uncut DNA strand acts as a template to permit healing without alteration of genetic material. Here, we examine the ability of a nicking variant of the I-SceI endonuclease (K223I I-SceI) to stimulate gene targeting in yeast Saccharomyces cerevisiae and in human embryonic kidney (HEK-293) cells. K223I I-SceI is proficient in both yeast and human cells and promotes gene correction up to 12-fold. We show that K223I I-SceI-driven recombination follows a different mechanism than wild-type I-SceI-driven recombination, thus indicating that the initial DNA break that stimulates recombination is not a low-level DSB but a nick. We also demonstrate that K223I I-SceI efficiently elevates gene targeting at loci distant from the break site in yeast cells. These findings establish the capability of the I-SceI nickase to enhance recombination in yeast and human cells, strengthening the notion that nicking enzymes could be effective tools in gene correction strategies for applications in molecular biology, biotechnology, and gene therapy. PMID:24558436

TALEN-mediated generation and genetic correction of disease-specific human induced pluripotent stem cells.

PubMed

Ramalingam, Sivaprakash; Annaluru, Narayana; Kandavelou, Karthikeyan; Chandrasegaran, Srinivasan

2014-01-01

Generation and precise genetic correction of patient-derived hiPSCs have great potential in regenerative medicine. Such targeted genetic manipulations can now be achieved using gene-editing nucleases. Here, we report generation of cystic fibrosis (CF) and Gaucher's disease (GD) hiPSCs respectively from CF (homozygous for CFTRΔF508 mutation) and Type II GD [homozygous for β-glucocerebrosidase (GBA) 1448T>C mutation] patient fibroblasts, using CCR5- specific TALENs. Site-specific addition of loxP-flanked Oct4/Sox2/Klf4/Lin28/Nanog/eGFP gene cassette at the endogenous CCR5 site of patient-derived disease-specific primary fibroblasts induced reprogramming, giving rise to both monoallele (heterozygous) and biallele CCR5-modified hiPSCs. Subsequent excision of the donor cassette was done by treating CCR5-modified CF and GD hiPSCs with Cre. We also demonstrate site-specific correction of sickle cell disease (SCD) mutations at the endogenous HBB locus of patient-specific hiPSCs [TNC1 line that is homozygous for mutated β- globin alleles (βS/βS)], using HBB-specific TALENs. SCD-corrected hiPSC lines showed gene conversion of the mutated βS to the wild-type βA in one of the HBB alleles, while the other allele remained a mutant phenotype. After excision of the loxP-flanked DNA cassette from the SCD-corrected hiPSC lines using Cre, we obtained secondary heterozygous βS/βA hiPSCs, which express the wild-type (βA) transcript to 30-40% level as compared to uncorrected (βS/βS) SCD hiPSCs when differentiated into erythroid cells. Furthermore, we also show that TALEN-mediated generation and genetic correction of disease-specific hiPSCs did not induce any off-target mutations at closely related sites.

Cleanups In My Community (CIMC) - Federal Facility RCRA Sites, National Layer

EPA Pesticide Factsheets

Federal facilities are properties owned by the federal government. This data layer provides access to Federal facilities that are Resource Conservation and Recovery Act (RCRA) sites as part of the CIMC web service. The Resource Conservation and Recovery Act, among other things, helps ensure that wastes are managed in an environmentally sound manner so as to protect human health and the environment from the potential hazards of waste disposal.In particular, RCRA tightly regulates all hazardous waste from cradle to grave. In general, all generators, transporters, treaters, storers, and disposers of hazardous waste are required to provide information about their activities to state environmental agencies. These agencies, in turn pass on the information to regional and national EPA offices. Accidents or other activities at facilities that treat, store or dispose of hazardous wastes have sometimes led to the release of hazardous waste or hazardous constituents into soil, ground water, surface water, or air. When that happens, the RCRA Corrective Action program is one program that may be used to accomplish the necessary cleanup.In Cleanups in My Community, you can map or list RCRA Corrective Action sites that are currently undergoing corrective action, sites for which a remedy has been selected, sites for which construction has been completed, and sites where the corrective action cleanup is complete. This data layer shows those RCRA sites that are located at Federa

Targeted gene addition in human CD34(+) hematopoietic cells for correction of X-linked chronic granulomatous disease.

PubMed

De Ravin, Suk See; Reik, Andreas; Liu, Pei-Qi; Li, Linhong; Wu, Xiaolin; Su, Ling; Raley, Castle; Theobald, Narda; Choi, Uimook; Song, Alexander H; Chan, Andy; Pearl, Jocelynn R; Paschon, David E; Lee, Janet; Newcombe, Hannah; Koontz, Sherry; Sweeney, Colin; Shivak, David A; Zarember, Kol A; Peshwa, Madhusudan V; Gregory, Philip D; Urnov, Fyodor D; Malech, Harry L

2016-04-01

Gene therapy with genetically modified human CD34(+) hematopoietic stem and progenitor cells (HSPCs) may be safer using targeted integration (TI) of transgenes into a genomic 'safe harbor' site rather than random viral integration. We demonstrate that temporally optimized delivery of zinc finger nuclease mRNA via electroporation and adeno-associated virus (AAV) 6 delivery of donor constructs in human HSPCs approaches clinically relevant levels of TI into the AAVS1 safe harbor locus. Up to 58% Venus(+) HSPCs with 6-16% human cell marking were observed following engraftment into mice. In HSPCs from patients with X-linked chronic granulomatous disease (X-CGD), caused by mutations in the gp91phox subunit of the NADPH oxidase, TI of a gp91phox transgene into AAVS1 resulted in ∼15% gp91phox expression and increased NADPH oxidase activity in ex vivo-derived neutrophils. In mice transplanted with corrected HSPCs, 4-11% of human cells in the bone marrow expressed gp91phox. This method for TI into AAVS1 may be broadly applicable to correction of other monogenic diseases.

Alternative derivation of an exchange-only density-functional optimized effective potential

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

Joubert, D. P.

2007-10-15

An alternative derivation of the exchange-only density-functional optimized effective potential equation is given. It is shown that the localized Hartree-Fock-common energy denominator Green's function approximation (LHF-CEDA) for the density-functional exchange potential proposed independently by Della Sala and Goerling [J. Chem. Phys. 115, 5718 (2001)] and Gritsenko and Baerends [Phys. Rev. A 64, 42506 (2001)] can be derived as an approximation to the OEP exchange potential in a similar way that the KLI approximation [Phys. Rev. A 45, 5453 (1992)] was derived. An exact expression for the correction term to the LHF-CEDA approximation can thus be found. The correction term canmore » be expressed in terms of the first-order perturbation-theory many-electron wave function shift when the Kohn-Sham Hamiltonian is subjected to a perturbation equal to the difference between the density-functional exchange potential and the Hartree-Fock nonlocal potential, expressed in terms of the Kohn-Sham orbitals. An explicit calculation shows that the density weighted mean of the correction term is zero, confirming that the LHF-CEDA approximation can be interpreted as a mean-field approximation. The corrected LHF-CEDA equation and the optimized effective potential equation are shown to be identical, with information distributed differently between terms in the equations. For a finite system the correction term falls off at least as fast as 1/r{sup 4} for large r.« less

Alternative derivation of an exchange-only density-functional optimized effective potential

NASA Astrophysics Data System (ADS)

Joubert, D. P.

2007-10-01

An alternative derivation of the exchange-only density-functional optimized effective potential equation is given. It is shown that the localized Hartree-Fock common energy denominator Green’s function approximation (LHF-CEDA) for the density-functional exchange potential proposed independently by Della Sala and Görling [J. Chem. Phys. 115, 5718 (2001)] and Gritsenko and Baerends [Phys. Rev. A 64, 42506 (2001)] can be derived as an approximation to the OEP exchange potential in a similar way that the KLI approximation [Phys. Rev. A 45, 5453 (1992)] was derived. An exact expression for the correction term to the LHF-CEDA approximation can thus be found. The correction term can be expressed in terms of the first-order perturbation-theory many-electron wave function shift when the Kohn-Sham Hamiltonian is subjected to a perturbation equal to the difference between the density-functional exchange potential and the Hartree-Fock nonlocal potential, expressed in terms of the Kohn-Sham orbitals. An explicit calculation shows that the density weighted mean of the correction term is zero, confirming that the LHF-CEDA approximation can be interpreted as a mean-field approximation. The corrected LHF-CEDA equation and the optimized effective potential equation are shown to be identical, with information distributed differently between terms in the equations. For a finite system the correction term falls off at least as fast as 1/r4 for large r .

The optimized effective potential and the self-interaction correction in density functional theory: Application to molecules

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

Garza, Jorge; Nichols, Jeffrey A.; Dixon, David A.

2000-05-08

The Krieger, Li, and Iafrate approximation to the optimized effective potential including the self-interaction correction for density functional theory has been implemented in a molecular code, NWChem, that uses Gaussian functions to represent the Kohn and Sham spin-orbitals. The differences between the implementation of the self-interaction correction in codes where planewaves are used with an optimized effective potential are discussed. The importance of the localization of the spin-orbitals to maximize the exchange-correlation of the self-interaction correction is discussed. We carried out exchange-only calculations to compare the results obtained with these approximations, and those obtained with the local spin density approximation,more » the generalized gradient approximation and Hartree-Fock theory. Interesting results for the energy difference (GAP) between the highest occupied molecular orbital, HOMO, and the lowest unoccupied molecular orbital, LUMO, (spin-orbital energies of closed shell atoms and molecules) using the optimized effective potential and the self-interaction correction have been obtained. The effect of the diffuse character of the basis set on the HOMO and LUMO eigenvalues at the various levels is discussed. Total energies obtained with the optimized effective potential and the self-interaction correction show that the exchange energy with these approximations is overestimated and this will be an important topic for future work. (c) 2000 American Institute of Physics.« less

Preclinical Demonstration of Lentiviral Vector-mediated Correction of Immunological and Metabolic Abnormalities in Models of Adenosine Deaminase Deficiency

PubMed Central

Carbonaro, Denise A; Zhang, Lin; Jin, Xiangyang; Montiel-Equihua, Claudia; Geiger, Sabine; Carmo, Marlene; Cooper, Aaron; Fairbanks, Lynette; Kaufman, Michael L; Sebire, Neil J; Hollis, Roger P; Blundell, Michael P; Senadheera, Shantha; Fu, Pei-Yu; Sahaghian, Arineh; Chan, Rebecca Y; Wang, Xiaoyan; Cornetta, Kenneth; Thrasher, Adrian J; Kohn, Donald B; Gaspar, H Bobby

2014-01-01

Gene transfer into autologous hematopoietic stem cells by γ-retroviral vectors (gRV) is an effective treatment for adenosine deaminase (ADA)–deficient severe combined immunodeficiency (SCID). However, current gRV have significant potential for insertional mutagenesis as reported in clinical trials for other primary immunodeficiencies. To improve the efficacy and safety of ADA-SCID gene therapy (GT), we generated a self-inactivating lentiviral vector (LV) with a codon-optimized human cADA gene under the control of the short form elongation factor-1α promoter (LV EFS ADA). In ADA−/− mice, LV EFS ADA displayed high-efficiency gene transfer and sufficient ADA expression to rescue ADA−/− mice from their lethal phenotype with good thymic and peripheral T- and B-cell reconstitution. Human ADA-deficient CD34+ cells transduced with 1–5 × 107 TU/ml had 1–3 vector copies/cell and expressed 1–2x of normal endogenous levels of ADA, as assayed in vitro and by transplantation into immune-deficient mice. Importantly, in vitro immortalization assays demonstrated that LV EFS ADA had significantly less transformation potential compared to gRV vectors, and vector integration-site analysis by nrLAM-PCR of transduced human cells grown in immune-deficient mice showed no evidence of clonal skewing. These data demonstrated that the LV EFS ADA vector can effectively transfer the human ADA cDNA and promote immune and metabolic recovery, while reducing the potential for vector-mediated insertional mutagenesis. PMID:24256635

In Vivo Quantification of Human Serotonin 1A Receptor Using 11C-CUMI-101, an Agonist PET Radiotracer

PubMed Central

Milak, Matthew S.; DeLorenzo, Christine; Zanderigo, Francesca; Prabhakaran, Jaya; Kumar, J.S. Dileep; Majo, Vattoly J.; Mann, J. John; Parsey, Ramin V.

2013-01-01

The serotonin (5-hydroxytryptamine, or 5-HT) type 1A receptor (5-HT1AR) is implicated in the pathophysiology of numerous neuropsychiatric disorders. We have published the initial evaluation and reproducibility in vivo of [O-methyl-11C]2-(4-(4-(2-methoxyphenyl)piperazin-1-yl)butyl)-4-methyl-1,2,4-triazine-3,5 (2H,4H)dione (11C-CUMI-101), a novel 5-HT1A agonist radiotracer, in Papio anubis. Here, we report the optimal modeling parameters of 11C-CUMI-101 for human PET studies. Methods PET scans were obtained for 7 adult human volunteers. 11C-CUMI-101 was injected as an intravenous bolus, and emission data were collected for 120 min in 3-dimensional mode. We evaluated 10 different models using metabolite-corrected arterial input functions or reference region approaches and several outcome measures. Results When using binding potential (BPF = Bavail/KD [total available receptor concentration divided by the equilibrium dissociation constant]) as the outcome measure, the likelihood estimation in the graphical analysis (LEGA) model performed slightly better than the other methods evaluated at full scan duration. The average test–retest percentage difference was 9.90% ± 5.60%. When using BPND (BPND = fnd × Bavail/KD; BPND equals the product of BPF and fnd [free fraction in the nondisplaceable compartment]), the simplified reference tissue method (SRTM) achieved the lowest percentage difference and smallest bias when compared with nondisplaceable binding potential obtained from LEGA using the metabolite-corrected plasma input function (r2 = 0.99; slope = 0.92). The time–stability analysis indicates that a 120-min scan is sufficient for the stable estimation of outcome measures. Voxel results were comparable to region-of-interest–based analysis, with higher spatial resolution. Conclusion On the basis of its measurable and stable free fraction, high affinity and selectivity, good blood–brain barrier permeability, and plasma and brain kinetics, 11C-CUMI-101 is suitable for the imaging of high-affinity 5-HT1A binding in humans. PMID:21098796

Loop corrections in double field theory: non-trivial dilaton potentials

NASA Astrophysics Data System (ADS)

Lv, Songlin; Wu, Houwen; Yang, Haitang

2014-10-01

It is believed that the invariance of the generalised diffeomorphisms prevents any non-trivial dilaton potential from double field theory. It is therefore difficult to include loop corrections in the formalism. We show that by redefining a non-local dilaton field, under strong constraint which is necessary to preserve the gauge invariance of double field theory, the theory does permit non-constant dilaton potentials and loop corrections. If the fields have dependence on only one single coordinate, the non-local dilaton is identical to the ordinary one with an additive constant.

Phenylquinoxalinone CFTR activator as potential prosecretory therapy for constipation

PubMed Central

CIL, ONUR; PHUAN, PUAY-WAH; SON, JUNG-HO; ZHU, JIE S.; KU, COLTON K.; TABIB, NILOUFAR AKHAVAN; TEUTHORN, ANDREW P.; FERRERA, LORETTA; ZACHOS, NICHOLAS C.; LIN, RUXIAN; GALIETTA, LUIS J. V.; DONOWITZ, MARK; KURTH, MARK J.; VERKMAN, ALAN S.

2017-01-01

Constipation is a common condition for which current treatments can have limited efficacy. By high-throughput screening, we recently identified a phenylquinoxalinone activator of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel that stimulated intestinal fluid secretion and normalized stool output in a mouse model of opioid-induced constipation. Here, we report phenylquinoxalinone structure-activity analysis, mechanism of action, animal efficacy data in acute and chronic models of constipation, and functional data in ex vivo primary cultured human enterocytes. Structure-activity analysis was done on 175 phenylquinoxalinone analogs, including 15 synthesized compounds. The most potent compound, CFTRact-J027, activated CFTR with EC50 ~ 200 nM, with patch-clamp analysis showing a linear CFTR current-voltage relationship with direct CFTR activation. CFTRact-J027 corrected reduced stool output and hydration in a mouse model of acute constipation produced by scopolamine and in a chronically constipated mouse strain (C3H/HeJ). Direct comparison with the approved prosecretory drugs lubiprostone and linaclotide showed substantially greater intestinal fluid secretion with CFTRact-J027, as well as greater efficacy in a constipation model. As evidence to support efficacy in human constipation, CFTRact-J027 increased transepithelial fluid transport in enteroids generated from normal human small intestine. Also, CFTRact-J027 was rapidly metabolized in vitro in human hepatic microsomes, suggesting minimal systemic exposure upon oral administration. These data establish structure-activity and mechanistic data for phenylquinoxalinone CFTR activators, and support their potential efficacy in human constipation. PMID:27815136

77 FR 22788 - Advisory Committee on Breast Cancer in Young Women (ACBCYW); Correction

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-17

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention Advisory Committee on Breast Cancer in Young Women (ACBCYW); Correction Correction: This notice was published in the Federal Register on March 20, 2012, Volume 77, Number 54, Page 16232. The meeting time and date listed...

Corrections in Montana: A Consultation on Corrections in Montana.

ERIC Educational Resources Information Center

Montana State Advisory Committee to the U.S. Commission on Civil Rights, Helena.

The findings and recommendations of a two-day conference on the civil and human rights of inmates of Montana's correctional institutions are contained in this report. The views of private citizens and experts from local, state, and federal organizations are presented in edited form under seven subject headings: existing prison reform legislation,…

Genome Editing of Monogenic Neuromuscular Diseases: A Systematic Review.

PubMed

Long, Chengzu; Amoasii, Leonela; Bassel-Duby, Rhonda; Olson, Eric N

2016-11-01

Muscle weakness, the most common symptom of neuromuscular disease, may result from muscle dysfunction or may be caused indirectly by neuronal and neuromuscular junction abnormalities. To date, more than 780 monogenic neuromuscular diseases, linked to 417 different genes, have been identified in humans. Genome-editing methods, especially the CRISPR (clustered regularly interspaced short palindromic repeats)-Cas9 (CRISPR-associated protein 9) system, hold clinical potential for curing many monogenic disorders, including neuromuscular diseases such as Duchenne muscular dystrophy, spinal muscular atrophy, amyotrophic lateral sclerosis, and myotonic dystrophy type 1. To provide an overview of genome-editing approaches; to summarize published reports on the feasibility, efficacy, and safety of current genome-editing methods as they relate to the potential correction of monogenic neuromuscular diseases; and to highlight scientific and clinical opportunities and obstacles toward permanent correction of disease-causing mutations responsible for monogenic neuromuscular diseases by genome editing. PubMed and Google Scholar were searched for articles published from June 30, 1989, through June 9, 2016, using the following keywords: genome editing, CRISPR-Cas9, neuromuscular disease, Duchenne muscular dystrophy, spinal muscular atrophy, amyotrophic lateral sclerosis, and myotonic dystrophy type 1. The following sources were reviewed: 341 articles describing different approaches to edit mammalian genomes; 330 articles describing CRISPR-Cas9-mediated genome editing in cell culture lines (in vitro) and animal models (in vivo); 16 websites used to generate single-guide RNA; 4 websites for off-target effects; and 382 articles describing viral and nonviral delivery systems. Articles describing neuromuscular diseases, including Duchenne muscular dystrophy, spinal muscular atrophy, amyotrophic lateral sclerosis, and myotonic dystrophy type 1, were also reviewed. Multiple proof-of-concept studies reveal the feasibility and efficacy of genome-editing-meditated correction of monogenic neuromuscular diseases in cultured cells and animal models. Genome editing is a rapidly evolving technology with enormous translational potential once efficacy, delivery, and safety issues are addressed. The clinical impact of this technology is that genome editing can permanently correct disease-causing mutations and circumvent the hurdles of traditional gene- and cell-based therapies.

Genome Editing of Monogenic Neuromuscular Diseases

PubMed Central

Long, Chengzu; Amoasii, Leonela; Bassel-Duby, Rhonda; Olson, Eric N.

2017-01-01

IMPORTANCE Muscle weakness, the most common symptom of neuromuscular disease, may result from muscle dysfunction or may be caused indirectly by neuronal and neuromuscular junction abnormalities. To date, more than 780 monogenic neuromuscular diseases, linked to 417 different genes, have been identified in humans. Genome-editing methods, especially the CRISPR (clustered regularly interspaced short palindromic repeats)–Cas9 (CRISPR-associated protein 9) system, hold clinical potential for curing many monogenic disorders, including neuromuscular diseases such as Duchenne muscular dystrophy, spinal muscular atrophy, amyotrophic lateral sclerosis, and myotonic dystrophy type 1. OBJECTIVES To provide an overview of genome-editing approaches; to summarize published reports on the feasibility, efficacy, and safety of current genome-editing methods as they relate to the potential correction of monogenic neuromuscular diseases; and to highlight scientific and clinical opportunities and obstacles toward permanent correction of disease-causing mutations responsible for monogenic neuromuscular diseases by genome editing. EVIDENCE REVIEW PubMed and Google Scholar were searched for articles published from June 30, 1989, through June 9, 2016, using the following keywords: genome editing, CRISPR-Cas9, neuromuscular disease, Duchenne muscular dystrophy, spinal muscular atrophy, amyotrophic lateral sclerosis, andmyotonic dystrophy type 1. The following sources were reviewed: 341 articles describing different approaches to edit mammalian genomes; 330 articles describing CRISPR-Cas9–mediated genome editing in cell culture lines (in vitro) and animal models (in vivo); 16 websites used to generate single-guide RNA; 4 websites for off-target effects; and 382 articles describing viral and nonviral delivery systems. Articles describing neuromuscular diseases, including Duchenne muscular dystrophy, spinal muscular atrophy, amyotrophic lateral sclerosis, and myotonic dystrophy type 1, were also reviewed. FINDINGS Multiple proof-of-concept studies reveal the feasibility and efficacy of genome-editing–meditated correction of monogenic neuromuscular diseases in cultured cells and animal models. CONCLUSIONS AND RELEVANCE Genome editing is a rapidly evolving technology with enormous translational potential once efficacy, delivery, and safety issues are addressed. The clinical impact of this technology is that genome editing can permanently correct disease-causing mutations and circumvent the hurdles of traditional gene- and cell-based therapies. PMID:27668807

First External Quality Assessment of Molecular and Serological Detection of Rift Valley Fever in the Western Mediterranean Region

PubMed Central

Monaco, Federica; Cosseddu, Gian Mario; Doumbia, Baba; Madani, Hafsa; El Mellouli, Fatiha; Jiménez-Clavero, Miguel Angel; Sghaier, Soufien; Marianneau, Philippe; Cetre-Sossah, Catherine; Polci, Andrea; Lacote, Sandra; Lakhdar, Magtouf; Fernandez-Pinero, Jovita; Sari Nassim, Chabane; Pinoni, Chiara; Capobianco Dondona, Andrea; Gallardo, Carmina; Bouzid, Taoufiq; Conte, Annamaria; Bortone, Grazia; Savini, Giovanni; Petrini, Antonio; Puech, Lilian

2015-01-01

Rift Valley fever (RVF) is a mosquito-borne viral zoonosis which affects humans and a wide range of domestic and wild ruminants. The large spread of RVF in Africa and its potential to emerge beyond its geographic range requires the development of surveillance strategies to promptly detect the disease outbreaks in order to implement efficient control measures, which could prevent the widespread of the virus to humans. The Animal Health Mediterranean Network (REMESA) linking some Northern African countries as Algeria, Egypt, Libya, Mauritania, Morocco, Tunisia with Southern European ones as France, Italy, Portugal and Spain aims at improving the animal health in the Western Mediterranean Region since 2009. In this context, a first assessment of the diagnostic capacities of the laboratories involved in the RVF surveillance was performed. The first proficiency testing (external quality assessment—EQA) for the detection of the viral genome and antibodies of RVF virus (RVFV) was carried out from October 2013 to February 2014. Ten laboratories participated from 6 different countries (4 from North Africa and 2 from Europe). Six laboratories participated in the ring trial for both viral RNA and antibodies detection methods, while four laboratories participated exclusively in the antibodies detection ring trial. For the EQA targeting the viral RNA detection methods 5 out of 6 laboratories reported 100% of correct results. One laboratory misidentified 2 positive samples as negative and 3 positive samples as doubtful indicating a need for corrective actions. For the EQA targeting IgG and IgM antibodies methods 9 out of the 10 laboratories reported 100% of correct results, whilst one laboratory reported all correct results except one false-positive. These two ring trials provide evidence that most of the participating laboratories are capable to detect RVF antibodies and viral RNA thus recognizing RVF infection in affected ruminants with the diagnostic methods currently available. PMID:26566248

First External Quality Assessment of Molecular and Serological Detection of Rift Valley Fever in the Western Mediterranean Region.

PubMed

Monaco, Federica; Cosseddu, Gian Mario; Doumbia, Baba; Madani, Hafsa; El Mellouli, Fatiha; Jiménez-Clavero, Miguel Angel; Sghaier, Soufien; Marianneau, Philippe; Cetre-Sossah, Catherine; Polci, Andrea; Lacote, Sandra; Lakhdar, Magtouf; Fernandez-Pinero, Jovita; Sari Nassim, Chabane; Pinoni, Chiara; Capobianco Dondona, Andrea; Gallardo, Carmina; Bouzid, Taoufiq; Conte, Annamaria; Bortone, Grazia; Savini, Giovanni; Petrini, Antonio; Puech, Lilian

2015-01-01

Rift Valley fever (RVF) is a mosquito-borne viral zoonosis which affects humans and a wide range of domestic and wild ruminants. The large spread of RVF in Africa and its potential to emerge beyond its geographic range requires the development of surveillance strategies to promptly detect the disease outbreaks in order to implement efficient control measures, which could prevent the widespread of the virus to humans. The Animal Health Mediterranean Network (REMESA) linking some Northern African countries as Algeria, Egypt, Libya, Mauritania, Morocco, Tunisia with Southern European ones as France, Italy, Portugal and Spain aims at improving the animal health in the Western Mediterranean Region since 2009. In this context, a first assessment of the diagnostic capacities of the laboratories involved in the RVF surveillance was performed. The first proficiency testing (external quality assessment--EQA) for the detection of the viral genome and antibodies of RVF virus (RVFV) was carried out from October 2013 to February 2014. Ten laboratories participated from 6 different countries (4 from North Africa and 2 from Europe). Six laboratories participated in the ring trial for both viral RNA and antibodies detection methods, while four laboratories participated exclusively in the antibodies detection ring trial. For the EQA targeting the viral RNA detection methods 5 out of 6 laboratories reported 100% of correct results. One laboratory misidentified 2 positive samples as negative and 3 positive samples as doubtful indicating a need for corrective actions. For the EQA targeting IgG and IgM antibodies methods 9 out of the 10 laboratories reported 100% of correct results, whilst one laboratory reported all correct results except one false-positive. These two ring trials provide evidence that most of the participating laboratories are capable to detect RVF antibodies and viral RNA thus recognizing RVF infection in affected ruminants with the diagnostic methods currently available.

A rapid method for selecting suitable animal species for studying pathogen interactions with plasma protein ligands in vivo.

PubMed

Naudin, Clément; Schumski, Ariane; Salo-Ahen, Outi M H; Herwald, Heiko; Smeds, Emanuel

2017-05-01

Species tropism constitutes a serious problem for developing relevant animal models of infection. Human pathogens can express virulence factors that show specific selectivity to human proteins, while their affinity for orthologs from other species can vary significantly. Suitable animal species must be used to analyse whether virulence factors are potential targets for drug development. We developed an assay that rapidly predicts applicable animal species for studying virulence factors binding plasma proteins. We used two well-characterized Staphylococcus aureus proteins, SSL7 and Efb, to develop an ELISA-based inhibition assay using plasma from different animal species. The interaction between SSL7 and human C5 and the binding of Efb to human fibrinogen and human C3 was studied. Affinity experiments and Western blot analyses were used to validate the assay. Human, monkey and cat plasma interfered with binding of SSL7 to human C5. Binding of Efb to human fibrinogen was blocked in human, monkey, gerbil and pig plasma, while human, monkey, gerbil, rabbit, cat and guinea pig plasma inhibited the binding of Efb to human C3. These results emphasize the importance of choosing correct animal models, and thus, our approach is a rapid and cost-effective method that can be used to prevent unnecessary animal experiments. © 2017 The Authors. Microbial Biotechnology published by John Wiley & Sons Ltd and Society for Applied Microbiology.

[Continuous registration of micropotentials of the human heart. Initial experiences with a new high resolution ECG amplifier system].

PubMed

Hombach, V; Kebbel, U; Höpp, H W; Winter, U J; Braun, V; Deutsch, H; Hirche, H; Hilger, H H

1982-12-24

A new ECG-amplifier system for recording cardiac microvolt potentials from the body surface is described. The improvement in signal-to-noise ratio was achieved by using specially designed suction electrodes, which were isolated from each other; by applying parallel signal averaging from four electrode pairs via four low-noise amplifiers; and by conducting the registration in Faraday cage. in 14 normal subjects, 12 patients with coronary heart disease and one patient with surgically corrected ventricular septal defect and pulmonary stenosis, pre-P-potentials (possible sinus node activity), His bundle potentials and ventricular late potentials were recorded with differing degrees of success. Variations of the time intervals to the preceding QRS complex were observed within the S-T segment in six of nine patients with demonstrable ventricular late ventricular late potentials. The advantage of such continuously recording ECG system lies in the highly accurate registration of cardiac micropotentials, particularly with ventricular late potentials that are changing in time, whereas the signal-averaging technique does not provide such possibilities.

Dissociation of diatomic molecules and the exact-exchange Kohn-Sham potential: the case of LiF

NASA Astrophysics Data System (ADS)

Makmal, Adi; Kuemmel, Stephan; Kronik, Leeor

2011-03-01

The incorrect fractional-charge dissociation of stretched diatomic molecules, predicted by semi-local exchange-correlation functionals, is revisited. This difficulty can be overcome with asymptotically correct non-local potential operators, but should also be absent in exact Kohn-Sham theory, where the potential is local. Here, we show, for the illustrative case of the LiF dimer, that the exact-exchange local Kohn-Sham potential, constructed within the Krieger, Li, and Iafrate (KLI) approximation, can lead to binding energy and charge dissociation curves that are qualitatively correct. This correct behavior is traced back to a characteristic ``step'' structure in the local exchange potential and its relation to the Kohn-Sham eigenvalues is analyzed.

Quantitative evaluation of first-order retardation corrections to the quarkonium spectrum

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

Brambilla, N.; Prosperi, G.M.

1992-08-01

We evaluate numerically first-order retardation corrections for some charmonium and bottomonium masses under the usual assumption of a Bethe-Salpeter purely scalar confinement kernel. The result depends strictly on the use of an additional effective potential to express the corrections (rather than to resort to Kato perturbation theory) and on an appropriate regularization prescription. The kernel has been chosen in order to reproduce in the instantaneous approximation a semirelativistic potential suggested by the Wilson loop method. The calculations are performed for two sets of parameters determined by fits in potential theory. The corrections turn out to be typically of the ordermore » of a few hundred MeV and depend on an additional scale parameter introduced in the regularization. A conjecture existing in the literature on the origin of the constant term in the potential is also discussed.« less

[Gene therapy for the treatment of inborn errors of metabolism].

PubMed

Pérez-López, Jordi

2014-06-16

Due to the enzymatic defect in inborn errors of metabolism, there is a blockage in the metabolic pathways and an accumulation of toxic metabolites. Currently available therapies include dietary restriction, empowering of alternative metabolic pathways, and the replacement of the deficient enzyme by cell transplantation, liver transplantation or administration of the purified enzyme. Gene therapy, using the transfer in the body of the correct copy of the altered gene by a vector, is emerging as a promising treatment. However, the difficulty of vectors currently used to cross the blood brain barrier, the immune response, the cellular toxicity and potential oncogenesis are some limitations that could greatly limit its potential clinical application in human beings. Copyright © 2013 Elsevier España, S.L. All rights reserved.

A Review of the Current Status of Relevant Zoonotic Pathogens in Wild Swine (Sus scrofa) Populations: Changes Modulating the Risk of Transmission to Humans.

PubMed

Ruiz-Fons, F

2017-02-01

Many wild swine populations in different parts of the World have experienced an unprecedented demographic explosion that may result in increased exposure of humans to wild swine zoonotic pathogens. Interactions between humans and wild swine leading to pathogen transmission could come from different ways, being hunters and game professionals the most exposed to acquiring infections from wild swine. However, increasing human settlements in semi-natural areas, outdoor activities, socio-economic changes and food habits may increase the rate of exposure to wild swine zoonotic pathogens and to potentially emerging pathogens from wild swine. Frequent and increasing contact rate between humans and wild swine points to an increasing chance of zoonotic pathogens arising from wild swine to be transmitted to humans. Whether this frequent contact could lead to new zoonotic pathogens emerging from wild swine to cause human epidemics or emerging disease outbreaks is difficult to predict, and assessment should be based on thorough epidemiologic surveillance. Additionally, several gaps in knowledge on wild swine global population dynamics trends and wild swine-zoonotic pathogen interactions should be addressed to correctly assess the potential role of wild swine in the emergence of diseases in humans. In this work, viruses such as hepatitis E virus, Japanese encephalitis virus, Influenza virus and Nipah virus, and bacteria such as Salmonella spp., Shiga toxin-producing Escherichia coli, Campylobacter spp. and Leptospira spp. have been identified as the most prone to be transmitted from wild swine to humans on the basis of geographic spread in wild swine populations worldwide, pathogen circulation rates in wild swine populations, wild swine population trends in endemic areas, susceptibility of humans to infection, transmissibility from wild swine to humans and existing evidence of wild swine-human transmission events. © 2015 Blackwell Verlag GmbH.

Automatic Online Motor Control Is Intact in Parkinson's Disease With and Without Perceptual Awareness.

PubMed

Merritt, Kate E; Seergobin, Ken N; Mendonça, Daniel A; Jenkins, Mary E; Goodale, Melvyn A; MacDonald, Penny A

2017-01-01

In the double-step paradigm, healthy human participants automatically correct reaching movements when targets are displaced. Motor deficits are prominent in Parkinson's disease (PD) patients. In the lone investigation of online motor correction in PD using the double-step task, a recent study found that PD patients performed unconscious adjustments appropriately but seemed impaired for consciously-perceived modifications. Conscious perception of target movement was achieved by linking displacement to movement onset. PD-related bradykinesia disproportionately prolonged preparatory phases for movements to original target locations for patients, potentially accounting for deficits. Eliminating this confound in a double-step task, we evaluated the effect of conscious awareness of trajectory change on online motor corrections in PD. On and off dopaminergic therapy, PD patients ( n = 14) and healthy controls ( n = 14) reached to peripheral visual targets that remained stationary or unexpectedly moved during an initial saccade. Saccade latencies in PD are comparable to controls'. Hence, target displacements occurred at equal times across groups. Target jump size affected conscious awareness, confirmed in an independent target displacement judgment task. Small jumps were subliminal, but large target displacements were consciously perceived. Contrary to the previous result, PD patients performed online motor corrections normally and automatically, irrespective of conscious perception. Patients evidenced equivalent movement durations for jump and stay trials, and trajectories for patients and controls were identical, irrespective of conscious perception. Dopaminergic therapy had no effect on performance. In summary, online motor control is intact in PD, unaffected by conscious perceptual awareness. The basal ganglia are not implicated in online corrective responses.

Automatic Online Motor Control Is Intact in Parkinson’s Disease With and Without Perceptual Awareness

PubMed Central

Seergobin, Ken N.; Mendonça, Daniel A.

2017-01-01

Abstract In the double-step paradigm, healthy human participants automatically correct reaching movements when targets are displaced. Motor deficits are prominent in Parkinson’s disease (PD) patients. In the lone investigation of online motor correction in PD using the double-step task, a recent study found that PD patients performed unconscious adjustments appropriately but seemed impaired for consciously-perceived modifications. Conscious perception of target movement was achieved by linking displacement to movement onset. PD-related bradykinesia disproportionately prolonged preparatory phases for movements to original target locations for patients, potentially accounting for deficits. Eliminating this confound in a double-step task, we evaluated the effect of conscious awareness of trajectory change on online motor corrections in PD. On and off dopaminergic therapy, PD patients (n = 14) and healthy controls (n = 14) reached to peripheral visual targets that remained stationary or unexpectedly moved during an initial saccade. Saccade latencies in PD are comparable to controls’. Hence, target displacements occurred at equal times across groups. Target jump size affected conscious awareness, confirmed in an independent target displacement judgment task. Small jumps were subliminal, but large target displacements were consciously perceived. Contrary to the previous result, PD patients performed online motor corrections normally and automatically, irrespective of conscious perception. Patients evidenced equivalent movement durations for jump and stay trials, and trajectories for patients and controls were identical, irrespective of conscious perception. Dopaminergic therapy had no effect on performance. In summary, online motor control is intact in PD, unaffected by conscious perceptual awareness. The basal ganglia are not implicated in online corrective responses. PMID:29085900

A Novel Spinal Implant for Fusionless Scoliosis Correction: A Biomechanical Analysis of the Motion Preserving Properties of a Posterior Periapical Concave Distraction Device

PubMed Central

Holewijn, Roderick M.; de Kleuver, Marinus; van der Veen, Albert J.; Emanuel, Kaj S.; Bisschop, Arno; Stadhouder, Agnita; van Royen, Barend J.

2017-01-01

Study Design: Biomechanical study. Objective: Recently, a posterior concave periapical distraction device for fusionless scoliosis correction was introduced. The goal of this study was to quantify the effect of the periapical distraction device on spinal range of motion (ROM) in comparison with traditional rigid pedicle screw-rod instrumentation. Methods: Using a spinal motion simulator, 6 human spines were loaded with 4 N m and 6 porcine spines with 2 N m to induce flexion-extension (FE), lateral bending (LB), and axial rotation (AR). ROM was measured in 3 conditions: untreated, periapical distraction device, and rigid pedicle screw-rod instrumentation. Results: The periapical distraction device caused a significant (P < .05) decrease in ROM of FE (human, −40.0% and porcine, −55.9%) and LB (human, −18.2% and porcine, −17.9%) as compared to the untreated spine, while ROM of AR remained unaffected. In comparison, rigid instrumentation caused a significantly (P < .05) larger decrease in ROM of FE (human, −80.9% and porcine, −94.0%), LB (human, −75.0% and porcine, −92.2%), and AR (human, −71.3% and porcine, −86.9%). Conclusions: Although no destructive forces were applied, no device failures were observed. Spinal ROM was significantly less constrained by the periapical distraction device compared to rigid pedicle screw-rod instrumentation. Therefore, provided that scoliosis correction is achieved, a more physiological spinal motion is expected after scoliosis correction with the posterior concave periapical distraction device. PMID:28811983

Corrective Action Investigation Plan for Corrective Action Unit 5: Landfills, Nevada Test Site, Nevada (Rev. No.: 0) includes Record of Technical Change No. 1 (dated 9/17/2002)

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

IT Corporation, Las Vegas, NV

This Corrective Action Investigation Plan contains the U.S. Department of Energy, National Nuclear Security Administration Nevada Operations Office's approach to collect the data necessary to evaluate corrective action alternatives appropriate for the closure of Corrective Action Unit (CAU) 5 under the Federal Facility Agreement and Consent Order. Corrective Action Unit 5 consists of eight Corrective Action Sites (CASs): 05-15-01, Sanitary Landfill; 05-16-01, Landfill; 06-08-01, Landfill; 06-15-02, Sanitary Landfill; 06-15-03, Sanitary Landfill; 12-15-01, Sanitary Landfill; 20-15-01, Landfill; 23-15-03, Disposal Site. Located between Areas 5, 6, 12, 20, and 23 of the Nevada Test Site (NTS), CAU 5 consists of unlined landfillsmore » used in support of disposal operations between 1952 and 1992. Large volumes of solid waste were produced from the projects which used the CAU 5 landfills. Waste disposed in these landfills may be present without appropriate controls (i.e., use restrictions, adequate cover) and hazardous and/or radioactive constituents may be present at concentrations and locations that could potentially pose a threat to human health and/or the environment. During the 1992 to 1995 time frame, the NTS was used for various research and development projects including nuclear weapons testing. Instead of managing solid waste at one or two disposal sites, the practice on the NTS was to dispose of solid waste in the vicinity of the project. A review of historical documentation, process knowledge, personal interviews, and inferred activities associated with this CAU identified the following as potential contaminants of concern: volatile organic compounds, semivolatile organic compounds, polychlorinated biphenyls, pesticides, petroleum hydrocarbons (diesel- and gasoline-range organics), Resource Conservation and Recovery Act Metals, plus nickel and zinc. A two-phase approach has been selected to collect information and generate data to satisfy needed resolution criteria and resolve the decision statements. Phase I will concentrate on geophysical surveys to confirm the presence or absence of disposed waste within a CAS and verify the boundaries of disposal areas; penetrate disposal feature covers via excavation and/or drilling; perform geodetic surveys; and be used to collect both soil and environmental samples for laboratory analyses. Phase II will deal only with those CASs where a contaminant of concern has been identified. This phase will involve the collection of additional soil and/or environmental samples for laboratory analyses. The results of this field investigation will support a defensible evaluation of corrective action alternatives in the corrective action decision document.« less

T1-weighted in vivo human whole brain MRI dataset with an ultrahigh isotropic resolution of 250 μm.

PubMed

Lüsebrink, Falk; Sciarra, Alessandro; Mattern, Hendrik; Yakupov, Renat; Speck, Oliver

2017-03-14

We present an ultrahigh resolution in vivo human brain magnetic resonance imaging (MRI) dataset. It consists of T 1 -weighted whole brain anatomical data acquired at 7 Tesla with a nominal isotropic resolution of 250 μm of a single young healthy Caucasian subject and was recorded using prospective motion correction. The raw data amounts to approximately 1.2 TB and was acquired in eight hours total scan time. The resolution of this dataset is far beyond any previously published in vivo structural whole brain dataset. Its potential use is to build an in vivo MR brain atlas. Methods for image reconstruction and image restoration can be improved as the raw data is made available. Pre-processing and segmentation procedures can possibly be enhanced for high magnetic field strength and ultrahigh resolution data. Furthermore, potential resolution induced changes in quantitative data analysis can be assessed, e.g., cortical thickness or volumetric measures, as high quality images with an isotropic resolution of 1 and 0.5 mm of the same subject are included in the repository as well.

Measurement and significance of sperm morphology

PubMed Central

Menkveld, Roelof; Holleboom, Cas AG; Rhemrev, Johann PT

2011-01-01

The measurement or evaluation and clinical significance of human sperm morphology has always been and still is a controversial aspect of the semen analysis for the determination of a male's fertility potential. In this review the background of the development of the evaluation criteria for sperm morphology will be discussed. Aspects of criticism on the strict criteria definition and use of the criteria for sperm morphology evaluation will be discussed as well as possible reasons for the decline in normal sperm morphology values and how we can compromise for this phenomenon resulting in the very low normal reference value as published in the 2010 WHO manual for the Examination and Processing of Human Semen. One of the possible solutions may be to give more attention to a limited number of abnormal sperm morphology categories and the inclusion of sperm morphology patterns. It is concluded in this review that if done correctly and with care and with strict application of existing guidelines as outlined in the 2010 WHO manual, sperm morphology measurement still has a very important role to play in the clinical evaluation of male fertility potential. PMID:21076438

T1-weighted in vivo human whole brain MRI dataset with an ultrahigh isotropic resolution of 250 μm

NASA Astrophysics Data System (ADS)

Lüsebrink, Falk; Sciarra, Alessandro; Mattern, Hendrik; Yakupov, Renat; Speck, Oliver

2017-03-01

We present an ultrahigh resolution in vivo human brain magnetic resonance imaging (MRI) dataset. It consists of T1-weighted whole brain anatomical data acquired at 7 Tesla with a nominal isotropic resolution of 250 μm of a single young healthy Caucasian subject and was recorded using prospective motion correction. The raw data amounts to approximately 1.2 TB and was acquired in eight hours total scan time. The resolution of this dataset is far beyond any previously published in vivo structural whole brain dataset. Its potential use is to build an in vivo MR brain atlas. Methods for image reconstruction and image restoration can be improved as the raw data is made available. Pre-processing and segmentation procedures can possibly be enhanced for high magnetic field strength and ultrahigh resolution data. Furthermore, potential resolution induced changes in quantitative data analysis can be assessed, e.g., cortical thickness or volumetric measures, as high quality images with an isotropic resolution of 1 and 0.5 mm of the same subject are included in the repository as well.

Non-animal assessment of skin sensitization hazard: Is an integrated testing strategy needed, and if so what should be integrated?

PubMed

Roberts, David W; Patlewicz, Grace

2018-01-01

There is an expectation that to meet regulatory requirements, and avoid or minimize animal testing, integrated approaches to testing and assessment will be needed that rely on assays representing key events (KEs) in the skin sensitization adverse outcome pathway. Three non-animal assays have been formally validated and regulatory adopted: the direct peptide reactivity assay (DPRA), the KeratinoSens™ assay and the human cell line activation test (h-CLAT). There have been many efforts to develop integrated approaches to testing and assessment with the "two out of three" approach attracting much attention. Here a set of 271 chemicals with mouse, human and non-animal sensitization test data was evaluated to compare the predictive performances of the three individual non-animal assays, their binary combinations and the "two out of three" approach in predicting skin sensitization potential. The most predictive approach was to use both the DPRA and h-CLAT as follows: (1) perform DPRA - if positive, classify as sensitizing, and (2) if negative, perform h-CLAT - a positive outcome denotes a sensitizer, a negative, a non-sensitizer. With this approach, 85% (local lymph node assay) and 93% (human) of non-sensitizer predictions were correct, whereas the "two out of three" approach had 69% (local lymph node assay) and 79% (human) of non-sensitizer predictions correct. The findings are consistent with the argument, supported by published quantitative mechanistic models that only the first KE needs to be modeled. All three assays model this KE to an extent. The value of using more than one assay depends on how the different assays compensate for each other's technical limitations. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Correction: Ambient temperature deposition of gallium nitride/gallium oxynitride from a deep eutectic electrolyte, under potential control.

PubMed

Sarkar, Sujoy; Sampath, S

2016-05-28

Correction for 'Ambient temperature deposition of gallium nitride/gallium oxynitride from a deep eutectic electrolyte, under potential control' by Sujoy Sarkar et al., Chem. Commun., 2016, 52, 6407-6410.

30 CFR 57.12030 - Correction of dangerous conditions.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Correction of dangerous conditions. 57.12030... Electricity Surface and Underground § 57.12030 Correction of dangerous conditions. When a potentially dangerous condition is found it shall be corrected before equipment or wiring is energized. ...

30 CFR 57.12030 - Correction of dangerous conditions.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Correction of dangerous conditions. 57.12030... Electricity Surface and Underground § 57.12030 Correction of dangerous conditions. When a potentially dangerous condition is found it shall be corrected before equipment or wiring is energized. ...

30 CFR 57.12030 - Correction of dangerous conditions.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Correction of dangerous conditions. 57.12030... Electricity Surface and Underground § 57.12030 Correction of dangerous conditions. When a potentially dangerous condition is found it shall be corrected before equipment or wiring is energized. ...

30 CFR 57.12030 - Correction of dangerous conditions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Correction of dangerous conditions. 57.12030... Electricity Surface and Underground § 57.12030 Correction of dangerous conditions. When a potentially dangerous condition is found it shall be corrected before equipment or wiring is energized. ...

30 CFR 57.12030 - Correction of dangerous conditions.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Correction of dangerous conditions. 57.12030... Electricity Surface and Underground § 57.12030 Correction of dangerous conditions. When a potentially dangerous condition is found it shall be corrected before equipment or wiring is energized. ...

Absorption spectroscopy setup for determination of whole human blood and blood-derived materials spectral characteristics

NASA Astrophysics Data System (ADS)

Wróbel, M. S.; Gnyba, M.; Milewska, D.; Mitura, K.; Karpienko, K.

2015-09-01

A dedicated absorption spectroscopy system was set up using tungsten-halogen broadband source, optical fibers, sample holder, and a commercial spectrometer with CCD array. Analysis of noise present in the setup was carried out. Data processing was applied to the absorption spectra to reduce spectral noise, and improve the quality of the spectra and to remove the baseline level. The absorption spectra were measured for whole blood samples, separated components: plasma, saline, washed erythrocytes in saline and human whole blood with biomarkers - biocompatible nanodiamonds (ND). Blood samples had been derived from a number of healthy donors. The results prove a correct setup arrangement, with adequate preprocessing of the data. The results of blood-ND mixtures measurements show no toxic effect on blood cells, which proves the NDs as a potential biocompatible biomarkers.

Automation in the graphic arts

NASA Astrophysics Data System (ADS)

Truszkowski, Walt

1995-04-01

The CHIMES (Computer-Human Interaction Models) tool was designed to help solve a simply-stated but important problem, i.e., the problem of generating a user interface to a system that complies with established human factors standards and guidelines. Though designed for use in a fairly restricted user domain, i.e., spacecraft mission operations, the CHIMES system is essentially domain independent and applicable wherever graphical user interfaces of displays are to be encountered. The CHIMES philosophy and operating strategy are quite simple. Instead of requiring a human designer to actively maintain in his or her head the now encyclopedic knowledge that human factors and user interface specialists have evolved, CHIMES incorporates this information in its knowledge bases. When directed to evaluated a design, CHIMES determines and accesses the appropriate knowledge, performs an evaluation of the design against that information, determines whether the design is compliant with the selected guidelines and suggests corrective actions if deviations from guidelines are discovered. This paper will provide an overview of the capabilities of the current CHIMES tool and discuss the potential integration of CHIMES-like technology in automated graphic arts systems.

21 CFR 806.20 - Records of corrections and removals not required to be reported.

Code of Federal Regulations, 2011 CFR

2011-04-01

... HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES MEDICAL DEVICES; REPORTS OF CORRECTIONS AND... known, and the intended use of the device. (2) The model, catalog, or code number of the device and the...) Each device manufacturer or importer who initiates a correction or removal of a device that is not...

21 CFR 806.20 - Records of corrections and removals not required to be reported.

Code of Federal Regulations, 2010 CFR

2010-04-01

... HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES MEDICAL DEVICES; REPORTS OF CORRECTIONS AND... known, and the intended use of the device. (2) The model, catalog, or code number of the device and the...) Each device manufacturer or importer who initiates a correction or removal of a device that is not...

49 CFR Appendix F to Part 227 - Calculations and Application of Age Corrections to Audiograms

Code of Federal Regulations, 2011 CFR

2011-10-01

... to Noise,” Department of Health and Human Services (NIOSH) Publication No. 98-126. For each...: Employee is a 32-year-old male. The audiometric history for his right ear is shown in decibels below... age correction). Table F-1—Age Correction Values in Decibels for Males Years Audiometric test...

Comprehension and utilisation of pointing gestures and gazing in dog-human communication in relatively complex situations.

PubMed

Lakatos, Gabriella; Gácsi, Márta; Topál, József; Miklósi, Adám

2012-03-01

The aim of the present investigation was to study the visual communication between humans and dogs in relatively complex situations. In the present research, we have modelled more lifelike situations in contrast to previous studies which often relied on using only two potential hiding locations and direct association between the communicative signal and the signalled object. In Study 1, we have provided the dogs with four potential hiding locations, two on each side of the experimenter to see whether dogs are able to choose the correct location based on the pointing gesture. In Study 2, dogs had to rely on a sequence of pointing gestures displayed by two different experimenters. We have investigated whether dogs are able to recognise an 'indirect signal', that is, a pointing toward a pointer. In Study 3, we have examined whether dogs can understand indirect information about a hidden object and direct the owner to the particular location. Study 1 has revealed that dogs are unlikely to rely on extrapolating precise linear vectors along the pointing arm when relying on human pointing gestures. Instead, they rely on a simple rule of following the side of the human gesturing. If there were more targets on the same side of the human, they showed a preference for the targets closer to the human. Study 2 has shown that dogs are able to rely on indirect pointing gestures but the individual performances suggest that this skill may be restricted to a certain level of complexity. In Study 3, we have found that dogs are able to localise the hidden object by utilising indirect human signals, and they are able to convey this information to their owner.

Use of wild bird surveillance, human case data and GIS spatial analysis for predicting spatial distributions of West Nile virus in Greece.

PubMed

Valiakos, George; Papaspyropoulos, Konstantinos; Giannakopoulos, Alexios; Birtsas, Periklis; Tsiodras, Sotirios; Hutchings, Michael R; Spyrou, Vassiliki; Pervanidou, Danai; Athanasiou, Labrini V; Papadopoulos, Nikolaos; Tsokana, Constantina; Baka, Agoritsa; Manolakou, Katerina; Chatzopoulos, Dimitrios; Artois, Marc; Yon, Lisa; Hannant, Duncan; Petrovska, Liljana; Hadjichristodoulou, Christos; Billinis, Charalambos

2014-01-01

West Nile Virus (WNV) is the causative agent of a vector-borne, zoonotic disease with a worldwide distribution. Recent expansion and introduction of WNV into new areas, including southern Europe, has been associated with severe disease in humans and equids, and has increased concerns regarding the need to prevent and control future WNV outbreaks. Since 2010, 524 confirmed human cases of the disease have been reported in Greece with greater than 10% mortality. Infected mosquitoes, wild birds, equids, and chickens have been detected and associated with human disease. The aim of our study was to establish a monitoring system with wild birds and reported human cases data using Geographical Information System (GIS). Potential distribution of WNV was modelled by combining wild bird serological surveillance data with environmental factors (e.g. elevation, slope, land use, vegetation density, temperature, precipitation indices, and population density). Local factors including areas of low altitude and proximity to water were important predictors of appearance of both human and wild bird cases (Odds Ratio = 1,001 95%CI = 0,723-1,386). Using GIS analysis, the identified risk factors were applied across Greece identifying the northern part of Greece (Macedonia, Thrace) western Greece and a number of Greek islands as being at highest risk of future outbreaks. The results of the analysis were evaluated and confirmed using the 161 reported human cases of the 2012 outbreak predicting correctly (Odds = 130/31 = 4,194 95%CI = 2,841-6,189) and more areas were identified for potential dispersion in the following years. Our approach verified that WNV risk can be modelled in a fast cost-effective way indicating high risk areas where prevention measures should be implemented in order to reduce the disease incidence.

Estimation of caffeine intake from analysis of caffeine metabolites in wastewater.

PubMed

Gracia-Lor, Emma; Rousis, Nikolaos I; Zuccato, Ettore; Bade, Richard; Baz-Lomba, Jose Antonio; Castrignanò, Erika; Causanilles, Ana; Hernández, Félix; Kasprzyk-Hordern, Barbara; Kinyua, Juliet; McCall, Ann-Kathrin; van Nuijs, Alexander L N; Plósz, Benedek G; Ramin, Pedram; Ryu, Yeonsuk; Santos, Miguel M; Thomas, Kevin; de Voogt, Pim; Yang, Zhugen; Castiglioni, Sara

2017-12-31

Caffeine metabolites in wastewater were investigated as potential biomarkers for assessing caffeine intake in a population. The main human urinary metabolites of caffeine were measured in the urban wastewater of ten European cities and the metabolic profiles in wastewater were compared with the human urinary excretion profile. A good match was found for 1,7-dimethyluric acid, an exclusive caffeine metabolite, suggesting that might be a suitable biomarker in wastewater for assessing population-level caffeine consumption. A correction factor was developed considering the percentage of excretion of this metabolite in humans, according to published pharmacokinetic studies. Daily caffeine intake estimated from wastewater analysis was compared with the average daily intake calculated from the average amount of coffee consumed by country per capita. Good agreement was found in some cities but further information is needed to standardize this approach. Wastewater analysis proved useful to providing additional local information on caffeine use. Copyright © 2017 Elsevier B.V. All rights reserved.

An automated image processing method for classification of diabetic retinopathy stages from conjunctival microvasculature images

NASA Astrophysics Data System (ADS)

Khansari, Maziyar M.; O'Neill, William; Penn, Richard; Blair, Norman P.; Chau, Felix; Shahidi, Mahnaz

2017-03-01

The conjunctiva is a densely vascularized tissue of the eye that provides an opportunity for imaging of human microcirculation. In the current study, automated fine structure analysis of conjunctival microvasculature images was performed to discriminate stages of diabetic retinopathy (DR). The study population consisted of one group of nondiabetic control subjects (NC) and 3 groups of diabetic subjects, with no clinical DR (NDR), non-proliferative DR (NPDR), or proliferative DR (PDR). Ordinary least square regression and Fisher linear discriminant analyses were performed to automatically discriminate images between group pairs of subjects. Human observers who were masked to the grouping of subjects performed image discrimination between group pairs. Over 80% and 70% of images of subjects with clinical and non-clinical DR were correctly discriminated by the automated method, respectively. The discrimination rates of the automated method were higher than human observers. The fine structure analysis of conjunctival microvasculature images provided discrimination of DR stages and can be potentially useful for DR screening and monitoring.

In vitro evaluation of a mammary gland specific expression vector encoding recombinant human lysozyme for development of transgenic dairy goat embryos.

PubMed

Gui, Tao; Zhang, Meiling; Chen, Jianwen; Zhang, Yuanliang; Zhou, Naru; Zhang, Yu; Tao, Jia; Sui, Liucai; Li, Yunsheng; Liu, Ya; Zhang, Xiaorong; Zhang, Yunhai

2012-08-01

A vector expressing human lysozyme (pBC1-hLYZ-GFP-Neo) was evaluated for gene and protein expression following liposome-mediated transformation of C-127 mouse mammary cancer cells. Cultures of G418-resistant clones were harvested 24-72 h after induction with prolactin, insulin and hydrocortisone. Target gene expression was analyzed by RT-PCR and Western blot and recombinant human lysozyme (rhLYZ) bacteriostatic activity was also evaluated. The hLYZ gene was correctly transcribed and translated in C-127 cells and hLYZ inhibited gram-positive bacterial growth, indicating the potential of this expression vector for development of a mammary gland bioreactor in goats. Guanzhong dairy goat skin fibroblasts transfected with pBC1-hLYZ-GFP-Neo were used to construct a goat embryo transgenically expressing rhLYZ by somatic nuclear transplantation with a blastocyst rate of 9.0 ± 2.8 %. These data establish the basis for cultivation of mastitis-resistant hLYZ transgenic goats.

Timing of target discrimination in human frontal eye fields.

PubMed

O'Shea, Jacinta; Muggleton, Neil G; Cowey, Alan; Walsh, Vincent

2004-01-01

Frontal eye field (FEF) neurons discharge in response to behaviorally relevant stimuli that are potential targets for saccades. Distinct visual and motor processes have been dissociated in the FEF of macaque monkeys, but little is known about the visual processing capacity of FEF in humans. We used double-pulse transcranial magnetic stimulation [(d)TMS] to investigate the timing of target discrimination during visual conjunction search. We applied dual TMS pulses separated by 40 msec over the right FEF and vertex. These were applied in five timing conditions to sample separate time windows within the first 200 msec of visual processing. (d)TMS impaired search performance, reflected in reduced d' scores. This effect was limited to a time window between 40 and 80 msec after search array onset. These parameters correspond with single-cell activity in FEF that predicts monkeys' behavioral reports on hit, miss, false alarm, and correct rejection trials. Our findings demonstrate a crucial early role for human FEF in visual target discrimination that is independent of saccade programming.

The event-related potential effects of cognitive conflict in a Chinese character-generation task.

PubMed

Qiu, Jiang; Zhang, Qinglin; Li, Hong; Luo, Yuejia; Yin, Qinging; Chen, Antao; Yuan, Hong

2007-06-11

High-density event-related potentials were recorded to examine the electrophysiologic correlates of the evaluation of possible answers provided during a Chinese character-generation task. We examined three conditions: the character given was what participants initially generated (Consistent answer), the character given was correct (Unexpected Correct answer), or it was incorrect (Unexpected Incorrect answer). Results showed that Unexpected Correct and Incorrect answers elicited a more negative event-related potential deflection (N320) than did Consistent answers between 300 and 400 ms. Dipole source analysis of difference waves (Unexpected Correct or Incorrect minus Consistent answers) localized the generator of the N320 in the anterior cingulate cortex. The N320 therefore likely reflects the cognitive change or conflict between old and new ways of thinking while identifying and judging characters.

Microsatellite polymorphisms associated with human behavioural and psychological phenotypes including a gene-environment interaction.

PubMed

Bagshaw, Andrew T M; Horwood, L John; Fergusson, David M; Gemmell, Neil J; Kennedy, Martin A

2017-02-03

The genetic and environmental influences on human personality and behaviour are a complex matter of ongoing debate. Accumulating evidence indicates that short tandem repeats (STRs) in regulatory regions are good candidates to explain heritability not accessed by genome-wide association studies. We tested for associations between the genotypes of four selected repeats and 18 traits relating to personality, behaviour, cognitive ability and mental health in a well-studied longitudinal birth cohort (n = 458-589) using one way analysis of variance. The repeats were a highly conserved poly-AC microsatellite in the upstream promoter region of the T-box brain 1 (TBR1) gene and three previously studied STRs in the activating enhancer-binding protein 2-beta (AP2-β) and androgen receptor (AR) genes. Where significance was found we used multiple regression to assess the influence of confounding factors. Carriers of the shorter, most common, allele of the AR gene's GGN microsatellite polymorphism had fewer anxiety-related symptoms, which was consistent with previous studies, but in our study this was not significant following Bonferroni correction. No associations with two repeats in the AP2-β gene withstood this correction. A novel finding was that carriers of the minor allele of the TBR1 AC microsatellite were at higher risk of conduct problems in childhood at age 7-9 (p = 0.0007, which did pass Bonferroni correction). Including maternal smoking during pregnancy (MSDP) in models controlling for potentially confounding influences showed that an interaction between TBR1 genotype and MSDP was a significant predictor of conduct problems in childhood and adolescence (p < 0.001), and of self-reported criminal behaviour up to age 25 years (p ≤ 0.02). This interaction remained significant after controlling for possible confounders including maternal age at birth, socio-economic status and education, and offspring birth weight. The potential functional importance of the TBR1 gene's promoter microsatellite deserves further investigation. Our results suggest that it participates in a gene-environment interaction with MDSP and antisocial behaviour. However, previous evidence that mothers who smoke during pregnancy carry genes for antisocial behaviour suggests that epistasis may influence the interaction.

Global Assessment of Exploitable Surface Reservoir Storage under Climate Change

NASA Astrophysics Data System (ADS)

Liu, L.; Parkinson, S.; Gidden, M.; Byers, E.; Satoh, Y.; Riahi, K.

2016-12-01

Surface water reservoirs provide us with reliable water supply systems, hydropower generation, flood control, and recreation services. Reliable reservoirs can be robust measures for water security and can help smooth out challenging seasonal variability of river flows. Yet, reservoirs also cause flow fragmentation in rivers and can lead to flooding of upstream areas, thereby displacing existing land-uses and ecosystems. The anticipated population growth, land use and climate change in many regions globally suggest a critical need to assess the potential for appropriate reservoir capacity that can balance rising demands with long-term water security. In this research, we assessed exploitable reservoir potential under climate change and human development constraints by deriving storage-yield relationships for 235 river basins globally. The storage-yield relationships map the amount of storage capacity required to meet a given water demand based on a 30-year inflow sequence. Runoff data is simulated with an ensemble of Global Hydrological Models (GHMs) for each of five bias-corrected general circulation models (GCMs) under four climate change pathways. These data are used to define future 30-year inflows in each river basin for time period between 2010 and 2080. The calculated capacity is then combined with geographical information of environmental and human development exclusion zones to further limit the storage capacity expansion potential in each basin. We investigated the reliability of reservoir potentials across different climate change scenarios and Shared Socioeconomic Pathways (SSPs) to identify river basins where reservoir expansion will be particularly challenging. Preliminary results suggest large disparities in reservoir potential across basins: some basins have already approached exploitable reserves, while some others display abundant potential. Exclusions zones pose significant impact on the amount of actual exploitable storage and firm yields worldwide: 30% of reservoir potential would be unavailable because of land occupation by environmental and human development. Results from this study will help decision makers to understand the reliability of infrastructure systems particularly sensitive to future water availability.

Some gating potentiators, including VX-770, diminish ΔF508-CFTR functional expression

PubMed Central

Veit, Guido; Avramescu, Radu G.; Perdomo, Doranda; Phuan, Puay-Wah; Bagdany, Miklos; Apaja, Pirjo M.; Borot, Florence; Szollosi, Daniel; Wu, Yu-Sheng; Finkbeiner, Walter E.; Hegedus, Tamas; Verkman, Alan S.; Lukacs, Gergely L.

2015-01-01

Cystic fibrosis (CF) is caused by mutations in the CF transmembrane regulator (CFTR) that result in reduced anion conductance at the apical membrane of secretory epithelia. Treatment of CF patients carrying the G551D gating mutation with the potentiator VX-770 (ivacaftor) largely restores channel activity and has shown substantial clinical benefit. However, most CF patients carry the ΔF508 mutation, which impairs CFTR folding, processing, function, and stability. Studies in homozygous ΔF508 CF patients indicated little clinical benefit of monotherapy with the investigational corrector VX-809 (lumacaftor) or VX-770, whereas combination clinical trials show limited but significant improvements in lung function. We show that VX-770, as well as most other potentiators, reduces the correction efficacy of VX-809 and another investigational corrector, VX-661. To mimic the administration of VX-770 alone or in combination with VX-809, we examined its long-term effect in immortalized and primary human respiratory epithelia. VX-770 diminished the folding efficiency and the metabolic stability of ΔF508-CFTR at the endoplasmic reticulum (ER) and post-ER compartments, respectively, causing reduced cell surface ΔF508-CFTR density and function. VX-770–induced destabilization of ΔF508-CFTR was influenced by second-site suppressor mutations of the folding defect and was prevented by stabilization of the nucleotide-binding domain 1 (NBD1)–NBD2 interface. The reduced correction efficiency of ΔF508-CFTR, as well as of two other processing mutations in the presence of VX-770, suggests the need for further optimization of potentiators to maximize the clinical benefit of corrector-potentiator combination therapy in CF. PMID:25101887

Some gating potentiators, including VX-770, diminish ΔF508-CFTR functional expression.

PubMed

Veit, Guido; Avramescu, Radu G; Perdomo, Doranda; Phuan, Puay-Wah; Bagdany, Miklos; Apaja, Pirjo M; Borot, Florence; Szollosi, Daniel; Wu, Yu-Sheng; Finkbeiner, Walter E; Hegedus, Tamas; Verkman, Alan S; Lukacs, Gergely L

2014-07-23

Cystic fibrosis (CF) is caused by mutations in the CF transmembrane regulator (CFTR) that result in reduced anion conductance at the apical membrane of secretory epithelia. Treatment of CF patients carrying the G551D gating mutation with the potentiator VX-770 (ivacaftor) largely restores channel activity and has shown substantial clinical benefit. However, most CF patients carry the ΔF508 mutation, which impairs CFTR folding, processing, function, and stability. Studies in homozygous ΔF508 CF patients indicated little clinical benefit of monotherapy with the investigational corrector VX-809 (lumacaftor) or VX-770, whereas combination clinical trials show limited but significant improvements in lung function. We show that VX-770, as well as most other potentiators, reduces the correction efficacy of VX-809 and another investigational corrector, VX-661. To mimic the administration of VX-770 alone or in combination with VX-809, we examined its long-term effect in immortalized and primary human respiratory epithelia. VX-770 diminished the folding efficiency and the metabolic stability of ΔF508-CFTR at the endoplasmic reticulum (ER) and post-ER compartments, respectively, causing reduced cell surface ΔF508-CFTR density and function. VX-770-induced destabilization of ΔF508-CFTR was influenced by second-site suppressor mutations of the folding defect and was prevented by stabilization of the nucleotide-binding domain 1 (NBD1)-NBD2 interface. The reduced correction efficiency of ΔF508-CFTR, as well as of two other processing mutations in the presence of VX-770, suggests the need for further optimization of potentiators to maximize the clinical benefit of corrector-potentiator combination therapy in CF. Copyright © 2014, American Association for the Advancement of Science.

Review and standardization of cell phone exposure calculations using the SAM phantom and anatomically correct head models.

PubMed

Beard, Brian B; Kainz, Wolfgang

2004-10-13

We reviewed articles using computational RF dosimetry to compare the Specific Anthropomorphic Mannequin (SAM) to anatomically correct models of the human head. Published conclusions based on such comparisons have varied widely. We looked for reasons that might cause apparently similar comparisons to produce dissimilar results. We also looked at the information needed to adequately compare the results of computational RF dosimetry studies. We concluded studies were not comparable because of differences in definitions, models, and methodology. Therefore we propose a protocol, developed by an IEEE standards group, as an initial step in alleviating this problem. The protocol calls for a benchmark validation study comparing the SAM phantom to two anatomically correct models of the human head. It also establishes common definitions and reporting requirements that will increase the comparability of all computational RF dosimetry studies of the human head.

CHISSL: A Human-Machine Collaboration Space for Unsupervised Learning

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

Arendt, Dustin L.; Komurlu, Caner; Blaha, Leslie M.

We developed CHISSL, a human-machine interface that utilizes supervised machine learning in an unsupervised context to help the user group unlabeled instances by her own mental model. The user primarily interacts via correction (moving a misplaced instance into its correct group) or confirmation (accepting that an instance is placed in its correct group). Concurrent with the user's interactions, CHISSL trains a classification model guided by the user's grouping of the data. It then predicts the group of unlabeled instances and arranges some of these alongside the instances manually organized by the user. We hypothesize that this mode of human andmore » machine collaboration is more effective than Active Learning, wherein the machine decides for itself which instances should be labeled by the user. We found supporting evidence for this hypothesis in a pilot study where we applied CHISSL to organize a collection of handwritten digits.« less

Review and standardization of cell phone exposure calculations using the SAM phantom and anatomically correct head models

PubMed Central

Beard, Brian B; Kainz, Wolfgang

2004-01-01

We reviewed articles using computational RF dosimetry to compare the Specific Anthropomorphic Mannequin (SAM) to anatomically correct models of the human head. Published conclusions based on such comparisons have varied widely. We looked for reasons that might cause apparently similar comparisons to produce dissimilar results. We also looked at the information needed to adequately compare the results of computational RF dosimetry studies. We concluded studies were not comparable because of differences in definitions, models, and methodology. Therefore we propose a protocol, developed by an IEEE standards group, as an initial step in alleviating this problem. The protocol calls for a benchmark validation study comparing the SAM phantom to two anatomically correct models of the human head. It also establishes common definitions and reporting requirements that will increase the comparability of all computational RF dosimetry studies of the human head. PMID:15482601

Experience-based human perception of facial expressions in Barbary macaques (Macaca sylvanus).

PubMed

Maréchal, Laëtitia; Levy, Xandria; Meints, Kerstin; Majolo, Bonaventura

2017-01-01

Facial expressions convey key cues of human emotions, and may also be important for interspecies interactions. The universality hypothesis suggests that six basic emotions (anger, disgust, fear, happiness, sadness, and surprise) should be expressed by similar facial expressions in close phylogenetic species such as humans and nonhuman primates. However, some facial expressions have been shown to differ in meaning between humans and nonhuman primates like macaques. This ambiguity in signalling emotion can lead to an increased risk of aggression and injuries for both humans and animals. This raises serious concerns for activities such as wildlife tourism where humans closely interact with wild animals. Understanding what factors (i.e., experience and type of emotion) affect ability to recognise emotional state of nonhuman primates, based on their facial expressions, can enable us to test the validity of the universality hypothesis, as well as reduce the risk of aggression and potential injuries in wildlife tourism. The present study investigated whether different levels of experience of Barbary macaques, Macaca sylvanus , affect the ability to correctly assess different facial expressions related to aggressive, distressed, friendly or neutral states, using an online questionnaire. Participants' level of experience was defined as either: (1) naïve: never worked with nonhuman primates and never or rarely encountered live Barbary macaques; (2) exposed: shown pictures of the different Barbary macaques' facial expressions along with the description and the corresponding emotion prior to undertaking the questionnaire; (3) expert: worked with Barbary macaques for at least two months. Experience with Barbary macaques was associated with better performance in judging their emotional state. Simple exposure to pictures of macaques' facial expressions improved the ability of inexperienced participants to better discriminate neutral and distressed faces, and a trend was found for aggressive faces. However, these participants, even when previously exposed to pictures, had difficulties in recognising aggressive, distressed and friendly faces above chance level. These results do not support the universality hypothesis as exposed and naïve participants had difficulties in correctly identifying aggressive, distressed and friendly faces. Exposure to facial expressions improved their correct recognition. In addition, the findings suggest that providing simple exposure to 2D pictures (for example, information signs explaining animals' facial signalling in zoos or animal parks) is not a sufficient educational tool to reduce tourists' misinterpretations of macaque emotion. Additional measures, such as keeping a safe distance between tourists and wild animals, as well as reinforcing learning via videos or supervised visits led by expert guides, could reduce such issues and improve both animal welfare and tourist experience.

Reliability of Craniofacial Superimposition Using Three-Dimension Skull Model.

PubMed

Gaudio, Daniel; Olivieri, Lara; De Angelis, Danilo; Poppa, Pasquale; Galassi, Andrea; Cattaneo, Cristina

2016-01-01

Craniofacial superimposition is a technique potentially useful for the identification of unidentified human remains if a photo of the missing person is available. We have tested the reliability of the 2D-3D computer-aided nonautomatic superimposition techniques. Three-dimension laser scans of five skulls and ten photographs were overlaid with an imaging software. The resulting superimpositions were evaluated using three methods: craniofacial landmarks, morphological features, and a combination of the two. A 3D model of each skull without its mandible was tested for superimposition; we also evaluated whether separating skulls by sex would increase correct identifications. Results show that the landmark method employing the entire skull is the more reliable one (5/5 correct identifications, 40% false positives [FP]), regardless of sex. However, the persistence of a high percentage of FP in all the methods evaluated indicates that these methods are unreliable for positive identification although the landmark-only method could be useful for exclusion. © 2015 American Academy of Forensic Sciences.

NAD+-Dependent Activation of Sirt1 Corrects the Phenotype in a Mouse Model of Mitochondrial Disease

PubMed Central

Cerutti, Raffaele; Pirinen, Eija; Lamperti, Costanza; Marchet, Silvia; Sauve, Anthony A.; Li, Wei; Leoni, Valerio; Schon, Eric A.; Dantzer, Françoise; Auwerx, Johan; Viscomi, Carlo; Zeviani, Massimo

2014-01-01

Summary Mitochondrial disorders are highly heterogeneous conditions characterized by defects of the mitochondrial respiratory chain. Pharmacological activation of mitochondrial biogenesis has been proposed as an effective means to correct the biochemical defects and ameliorate the clinical phenotype in these severely disabling, often fatal, disorders. Pathways related to mitochondrial biogenesis are targets of Sirtuin1, a NAD+-dependent protein deacetylase. As NAD+ boosts the activity of Sirtuin1 and other sirtuins, intracellular levels of NAD+ play a key role in the homeostatic control of mitochondrial function by the metabolic status of the cell. We show here that supplementation with nicotinamide riboside, a natural NAD+ precursor, or reduction of NAD+ consumption by inhibiting the poly(ADP-ribose) polymerases, leads to marked improvement of the respiratory chain defect and exercise intolerance of the Sco2 knockout/knockin mouse, a mitochondrial disease model characterized by impaired cytochrome c oxidase biogenesis. This strategy is potentially translatable into therapy of mitochondrial disorders in humans. PMID:24814483

Neural Correlates of User-initiated Motor Success and Failure - A Brain-Computer Interface Perspective.

PubMed

Yazmir, Boris; Reiner, Miriam

2018-05-15

Any motor action is, by nature, potentially accompanied by human errors. In order to facilitate development of error-tailored Brain-Computer Interface (BCI) correction systems, we focused on internal, human-initiated errors, and investigated EEG correlates of user outcome successes and errors during a continuous 3D virtual tennis game against a computer player. We used a multisensory, 3D, highly immersive environment. Missing and repelling the tennis ball were considered, as 'error' (miss) and 'success' (repel). Unlike most previous studies, where the environment "encouraged" the participant to perform a mistake, here errors happened naturally, resulting from motor-perceptual-cognitive processes of incorrect estimation of the ball kinematics, and can be regarded as user internal, self-initiated errors. Results show distinct and well-defined Event-Related Potentials (ERPs), embedded in the ongoing EEG, that differ across conditions by waveforms, scalp signal distribution maps, source estimation results (sLORETA) and time-frequency patterns, establishing a series of typical features that allow valid discrimination between user internal outcome success and error. The significant delay in latency between positive peaks of error- and success-related ERPs, suggests a cross-talk between top-down and bottom-up processing, represented by an outcome recognition process, in the context of the game world. Success-related ERPs had a central scalp distribution, while error-related ERPs were centro-parietal. The unique characteristics and sharp differences between EEG correlates of error/success provide the crucial components for an improved BCI system. The features of the EEG waveform can be used to detect user action outcome, to be fed into the BCI correction system. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Cryopreservation of Extracted Corneal Lenticules after Small Incision Lenticule Extraction for Potential Use in Human Subjects

PubMed Central

Ganesh, Sri; Rao, Pallavi A.

2014-01-01

Purpose: To describe the technique of cryopreservation of corneal lenticules extracted after small incision refractive lenticule extraction (ReLEx SMILE) and initial results of femtosecond laser intrastromal lenticular implantation for hyperopia. Methods: Lenticules were collected from patients undergoing ReLEx SMILE for the correction of myopia and subjected to a tissue processing technique and cryopreservation. These lenticules were subsequently used to treat 8 hyperopic eyes and 1 aphakic eye. A femtosecond laser was used to create a pocket into each patient's cornea, followed by implantation of a cryopreserved lenticule. The patients were monitored through follow-up examinations for a mean 155.4 days (38–310 days). Results: The mean interval from storage of lenticules to removal from liquid nitrogen was 96 days (range, 19–178 days). Mean spherical equivalent of hyperopic eyes treated was +4.50 ± 1.1 diopter (D). Mean keratometry and pachymetry changed from preoperative 43.9 D and 531.6 μm to 47.4 D and 605.2 μm, respectively, postoperatively. Mean residual spherical equivalent for hyperopic eyes was +0.6 D and +4.1 D for the aphakic eye. None of the eyes showed evidence of rejection or loss of best-corrected visual acuity at the end of the follow-up period. Conclusions: The cryopreservation technique seems to be a safe method of long-term storage of refractive lenticules extracted after ReLEx SMILE for use in allogeneic human subjects. It may potentially be a safe and effective alternative to excimer laser ablation for hyperopia because of the low risks of regression, haze, flap-related complications, postoperative dry eye, and higher-order aberrations. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: CTRI/2014/01/004331. PMID:25343698

Alternate corrections for estimating actual wetland evapotranspiration from potential evapotranspiration

USGS Publications Warehouse

Shoemaker, W. Barclay; Sumner, D.M.

2006-01-01

Corrections can be used to estimate actual wetland evapotranspiration (AET) from potential evapotranspiration (PET) as a means to define the hydrology of wetland areas. Many alternate parameterizations for correction coefficients for three PET equations are presented, covering a wide range of possible data-availability scenarios. At nine sites in the wetland Everglades of south Florida, USA, the relatively complex PET Penman equation was corrected to daily total AET with smaller standard errors than the PET simple and Priestley-Taylor equations. The simpler equations, however, required less data (and thus less funding for instrumentation), with the possibility of being corrected to AET with slightly larger, comparable, or even smaller standard errors. Air temperature generally corrected PET simple most effectively to wetland AET, while wetland stage and humidity generally corrected PET Priestley-Taylor and Penman most effectively to wetland AET. Stage was identified for PET Priestley-Taylor and Penman as the data type with the most correction ability at sites that are dry part of each year or dry part of some years. Finally, although surface water generally was readily available at each monitoring site, AET was not occurring at potential rates, as conceptually expected under well-watered conditions. Apparently, factors other than water availability, such as atmospheric and stomata resistances to vapor transport, also were limiting the PET rate. ?? 2006, The Society of Wetland Scientists.

ASXL1 mutation correction by CRISPR/Cas9 restores gene function in leukemia cells and increases survival in mouse xenografts

PubMed Central

Valletta, Simona; Dolatshad, Hamid; Bartenstein, Matthias; Yip, Bon Ham; Bello, Erica; Gordon, Shanisha; Yu, Yiting; Shaw, Jacqueline; Roy, Swagata; Scifo, Laura; Schuh, Anna; Pellagatti, Andrea; Fulga, Tudor A.; Verma, Amit; Boultwood, Jacqueline

2015-01-01

Recurrent somatic mutations of the epigenetic modifier and tumor suppressor ASXL1 are common in myeloid malignancies, including chronic myeloid leukemia (CML), and are associated with poor clinical outcome. CRISPR/Cas9 has recently emerged as a powerful and versatile genome editing tool for genome engineering in various species. We have used the CRISPR/Cas9 system to correct the ASXL1 homozygous nonsense mutation present in the CML cell line KBM5, which lacks ASXL1 protein expression. CRISPR/Cas9-mediated ASXL1 homozygous correction resulted in protein re-expression with restored normal function, including down-regulation of Polycomb repressive complex 2 target genes. Significantly reduced cell growth and increased myeloid differentiation were observed in ASXL1 mutation-corrected cells, providing new insights into the role of ASXL1 in human myeloid cell differentiation. Mice xenografted with mutation-corrected KBM5 cells showed significantly longer survival than uncorrected xenografts. These results show that the sole correction of a driver mutation in leukemia cells increases survival in vivo in mice. This study provides proof-of-concept for driver gene mutation correction via CRISPR/Cas9 technology in human leukemia cells and presents a strategy to illuminate the impact of oncogenic mutations on cellular function and survival. PMID:26623729

ASXL1 mutation correction by CRISPR/Cas9 restores gene function in leukemia cells and increases survival in mouse xenografts.

PubMed

Valletta, Simona; Dolatshad, Hamid; Bartenstein, Matthias; Yip, Bon Ham; Bello, Erica; Gordon, Shanisha; Yu, Yiting; Shaw, Jacqueline; Roy, Swagata; Scifo, Laura; Schuh, Anna; Pellagatti, Andrea; Fulga, Tudor A; Verma, Amit; Boultwood, Jacqueline

2015-12-29

Recurrent somatic mutations of the epigenetic modifier and tumor suppressor ASXL1 are common in myeloid malignancies, including chronic myeloid leukemia (CML), and are associated with poor clinical outcome. CRISPR/Cas9 has recently emerged as a powerful and versatile genome editing tool for genome engineering in various species. We have used the CRISPR/Cas9 system to correct the ASXL1 homozygous nonsense mutation present in the CML cell line KBM5, which lacks ASXL1 protein expression. CRISPR/Cas9-mediated ASXL1 homozygous correction resulted in protein re-expression with restored normal function, including down-regulation of Polycomb repressive complex 2 target genes. Significantly reduced cell growth and increased myeloid differentiation were observed in ASXL1 mutation-corrected cells, providing new insights into the role of ASXL1 in human myeloid cell differentiation. Mice xenografted with mutation-corrected KBM5 cells showed significantly longer survival than uncorrected xenografts. These results show that the sole correction of a driver mutation in leukemia cells increases survival in vivo in mice. This study provides proof-of-concept for driver gene mutation correction via CRISPR/Cas9 technology in human leukemia cells and presents a strategy to illuminate the impact of oncogenic mutations on cellular function and survival.

Correction of murine mucopolysaccharidosis VII by a human. beta. -glucuronidase transgene

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

Kyle, J.W.; Vogler, C.; Hoffmann, J.W.

1990-05-01

The authors recently described a murine model for mucopolysaccharidosis VII in mice that have an inherited deficiency of {beta}-glucuronidase. Affected mice, of genotype gus{sup mps}/gus{sup mps}, present clinical manifestations similar to those of humans with mucopolysaccharidosis VII (Sly syndrome) and are shown here to have secondary elevations of other lysosomal enzymes. The mucopolysaccharidosis VII phenotype in both species includes dwarfism, skeletal deformities, and premature death. Lysosome storage is visualized within enlarged vesicles and correlates biochemically with accumulation of undegraded and partially degraded glycosaminoglycans. In this report they describe the consequences of introducing the human {beta}-glucuronidase gene, GUSB, into gus{sup mps}/gus{supmore » mps} mice that produce virtually no murine {beta}-glucuronidase. Transgenic mice homozygous for the mucopolysaccharidosis VII mutation expressed high levels of human {beta}-glucuronidase activity in all tissues examined and were phenotypically normal. Biochemically, both the intralysosomal storage of glycosaminoglycans and the secondary elevation of other acid hydrolases were corrected. These findings demonstrate that the GUSB transgene is expressed in gus{sup mps}/gus{sup mps} mice and that human {beta}-glucuronidase corrects the murine mucopolysaccharidosis storage disease.« less

Targeted Gene Addition to a Safe Harbor locus in human CD34+ Hematopoietic Stem Cells for Correction of X-linked Chronic Granulomatous Disease

PubMed Central

De Ravin, Suk See; Reik, Andreas; Liu, Pei-Qi; Li, Linhong; Wu, Xiaolin; Su, Ling; Raley, Castle; Theobald, Narda; Choi, Uimook; Song, Alexander H.; Chan, Andy; Pearl, Jocelynn R.; Paschon, David E.; Lee, Janet; Newcombe, Hannah; Koontz, Sherry; Sweeney, Colin; Shivak, David A.; Zarember, Kol A.; Peshwa, Madhusudan V.; Gregory, Philip D.; Urnov, Fyodor D.; Malech, Harry L.

2016-01-01

Gene therapy with genetically modified human CD34+ hematopoietic stem cells (HSCs) may be safer using targeted integration (TI) of transgenes into a genomic ‘safe harbor’ site than random viral integration. We demonstrate that temporally optimized delivery of zinc finger nuclease mRNA via electroporation and adeno associated virus (AAV) 6 delivery of donor constructs in human HSCs approaches clinically relevant levels of TI into the AAVS1 safe harbor locus. Up to 58% Venus-positive HSCs with 6–16% human cell marking were observed following engraftment into mice. In HSCs from patients with X-linked chronic granulomatous disease (X-CGD), caused by mutations in the gp91phox subunit of the NADPH oxidase, TI of a gp91phox transgene into AAVS1 in resulted in ~15% gp91phox expression and increased NADPH oxidase activity in ex vivo–derived neutrophils. In mice transplanted with corrected HSCs, 4–11% of human cells in the bone marrow expressed gp91phox. This method for TI into AAVS1 may be broadly applicable to correction of other monogenic diseases. PMID:26950749

40 CFR 257.26 - Assessment of corrective measures.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 25 2011-07-01 2011-07-01 false Assessment of corrective measures. 257.26 Section 257.26 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES... potential impacts of appropriate potential remedies, including safety impacts, cross-media impacts, and...

40 CFR 257.26 - Assessment of corrective measures.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 24 2010-07-01 2010-07-01 false Assessment of corrective measures. 257.26 Section 257.26 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES... potential impacts of appropriate potential remedies, including safety impacts, cross-media impacts, and...

40 CFR 258.56 - Assessment of corrective measures.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 25 2011-07-01 2011-07-01 false Assessment of corrective measures. 258.56 Section 258.56 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES... implementation, and potential impacts of appropriate potential remedies, including safety impacts, cross-media...

Design Guidance for Computer-Based Procedures for Field Workers

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

Oxstrand, Johanna; Le Blanc, Katya; Bly, Aaron

Nearly all activities that involve human interaction with nuclear power plant systems are guided by procedures, instructions, or checklists. Paper-based procedures (PBPs) currently used by most utilities have a demonstrated history of ensuring safety; however, improving procedure use could yield significant savings in increased efficiency, as well as improved safety through human performance gains. The nuclear industry is constantly trying to find ways to decrease human error rates, especially human error rates associated with procedure use. As a step toward the goal of improving field workers’ procedure use and adherence and hence improve human performance and overall system reliability, themore » U.S. Department of Energy Light Water Reactor Sustainability (LWRS) Program researchers, together with the nuclear industry, have been investigating the possibility and feasibility of replacing current paper-based procedures with computer-based procedures (CBPs). PBPs have ensured safe operation of plants for decades, but limitations in paper-based systems do not allow them to reach the full potential for procedures to prevent human errors. The environment in a nuclear power plant is constantly changing, depending on current plant status and operating mode. PBPs, which are static by nature, are being applied to a constantly changing context. This constraint often results in PBPs that are written in a manner that is intended to cover many potential operating scenarios. Hence, the procedure layout forces the operator to search through a large amount of irrelevant information to locate the pieces of information relevant for the task and situation at hand, which has potential consequences of taking up valuable time when operators must be responding to the situation, and potentially leading operators down an incorrect response path. Other challenges related to use of PBPs are management of multiple procedures, place-keeping, finding the correct procedure for a task, and relying on other sources of additional information to ensure a functional and accurate understanding of the current plant status (Converse, 1995; Fink, Killian, Hanes, and Naser, 2009; Le Blanc, Oxstrand, and Waicosky, 2012). This report provides design guidance to be used when designing the human-system interaction and the design of the graphical user interface for a CBP system. The guidance is based on human factors research related to the design and usability of CBPs conducted by Idaho National Laboratory, 2012 - 2016.« less

The next generation of LASIK patients.

PubMed

Freeman, J Christopher; Chuck, Roy S

2009-07-01

With baby boomers aging, and despite a growing global population, there is a decreasing number of potential laser vision correction patients. Some believe that the worldwide economic downturn of these times will limit the number of potential patients as well. This article highlights looking to an alternative segment of the population to identify potential laser vision correction patients and the limitations of reaching this group. The group known as generation Y contains a large number of individuals who may be candidates for laser vision correction. Traditional marketing efforts present challenges in reaching this particular population segment. Many individuals in this group are already patients of eye doctors for contact lenses and glasses and can be reached by these eye doctors to address candidacy and education of laser vision correction. Generation Y represents a large population segment that contains technology-embracing individuals who, although hard to reach with traditional marketing efforts, may be reached by fellow eye doctors already managing these patients. There are many in this age group who would be good laser vision correction candidates.

Detection biases yield misleading patterns of species persistence and colonization in fragmented landscapes

USGS Publications Warehouse

Ruiz-Gutierrez, Viviana; Zipkin, Elise F.

2011-01-01

Species occurrence patterns, and related processes of persistence, colonization and turnover, are increasingly being used to infer habitat suitability, predict species distributions, and measure biodiversity potential. The majority of these studies do not account for observational error in their analyses despite growing evidence suggesting that the sampling process can significantly influence species detection and subsequently, estimates of occurrence. We examined the potential biases of species occurrence patterns that can result from differences in detectability across species and habitat types using hierarchical multispecies occupancy models applied to a tropical bird community in an agricultural fragmented landscape. Our results suggest that detection varies widely among species and habitat types. Not incorporating detectability severely biased occupancy dynamics for many species by overestimating turnover rates, producing misleading patterns of persistence and colonization of agricultural habitats, and misclassifying species into ecological categories (i.e., forest specialists and generalists). This is of serious concern, given that most research on the ability of agricultural lands to maintain current levels of biodiversity by and large does not correct for differences in detectability. We strongly urge researchers to apply an inferential framework which explicitly account for differences in detectability to fully characterize species-habitat relationships, correctly guide biodiversity conservation in human-modified landscapes, and generate more accurate predictions of species responses to future changes in environmental conditions.

Methods for the correction of vascular artifacts in PET O-15 water brain-mapping studies

NASA Astrophysics Data System (ADS)

Chen, Kewei; Reiman, E. M.; Lawson, M.; Yun, Lang-sheng; Bandy, D.; Palant, A.

1996-12-01

While positron emission tomographic (PET) measurements of regional cerebral blood flow (rCBF) can be used to map brain regions that are involved in normal and pathological human behaviors, measurements in the anteromedial temporal lobe can be confounded by the combined effects of radiotracer activity in neighboring arteries and partial-volume averaging. The authors now describe two simple methods to address this vascular artifact. One method utilizes the early frames of a dynamic PET study, while the other method utilizes a coregistered magnetic resonance image (MRI) to characterize the vascular region of interest (VROI). Both methods subsequently assign a common value to each pixel in the VROI for the control (baseline) scan and the activation scan. To study the vascular artifact and to demonstrate the ability of the proposed methods correcting the vascular artifact, four dynamic PET scans were performed in a single subject during the same behavioral state. For each of the four scans, a vascular scan containing vascular activity was computed as the summation of the images acquired 0-60 s after radiotracer administration, and a control scan containing minimal vascular activity was computed as the summation of the images acquired 20-80 s after radiotracer administration. t-score maps calculated from the four pairs of vascular and control scans were used to characterize regional blood flow differences related to vascular activity before and after the application of each vascular artifact correction method. Both methods eliminated the observed differences in vascular activity, as well as the vascular artifact observed in the anteromedial temporal lobes. Using PET data from a study of normal human emotion, these methods permitted the authors to identify rCBF increases in the anteromedial temporal lobe free from the potentially confounding, combined effects of vascular activity and partial-volume averaging.

Differences in the expression of endogenous efflux transporters in MDR1-transfected versus wildtype cell lines affect P-glycoprotein mediated drug transport

PubMed Central

Kuteykin-Teplyakov, Konstantin; Luna-Tortós, Carlos; Ambroziak, Kamila; Löscher, Wolfgang

2010-01-01

Background and purpose: P-glycoprotein (Pgp) efflux assays are widely used to identify Pgp substrates. The kidney cell lines Madin-Darby canine kidney (MDCK)-II and LLC-PK1, transfected with human MDR1 (ABCB1) are used to provide recombinant models of drug transport. Endogenous transporters in these cells may contribute to the activities of recombinant transporters, so that drug transport in MDR1-transfected cells is often corrected for the transport obtained in parental (wildtype) cells. However, expression of endogenous transporters may vary between transfected and wildtype cells, so that this correction may cause erroneous data. Here, we have measured the expression of endogenous efflux transporters in transfected and wildtype MDCK-II or LLC cells and the consequences for Pgp-mediated drug transport. Experimental approach: Using quantitative real-time RT-PCR, we determined the expression of endogenous Mdr1 mRNA and other efflux transporters in wildtype and MDR1-transfected MDCK-II and LLC cells. Transcellular transport was measured with the test substrate vinblastine. Key results: In MDR1-transfected MDCK cells, expression of endogenous (canine) Mdr1 and Mrp2 (Abcc2) mRNA was markedly lower than in wildtype cells, whereas MDR1-transfected LLC cells exhibited comparable Mdr1 but strikingly higher Mrp2 mRNA levels than wildtype cells. As a consequence, transport of vinblastine by human Pgp in efflux experiments was markedly underestimated when transport in MDR1-transfected MDCK cells was corrected for transport obtained in wildtype cells. This problem did not occur in LLC cells. Conclusions and implications: Differences in the expression of endogenous efflux transporters between transfected and wildtype MDCK cells provide a potential bias for in vitro studies on Pgp-mediated drug transport. PMID:20590635

Wide-field retinal optical coherence tomography with wavefront sensorless adaptive optics for enhanced imaging of targeted regions.

PubMed

Polans, James; Keller, Brenton; Carrasco-Zevallos, Oscar M; LaRocca, Francesco; Cole, Elijah; Whitson, Heather E; Lad, Eleonora M; Farsiu, Sina; Izatt, Joseph A

2017-01-01

The peripheral retina of the human eye offers a unique opportunity for assessment and monitoring of ocular diseases. We have developed a novel wide-field (>70°) optical coherence tomography system (WF-OCT) equipped with wavefront sensorless adaptive optics (WSAO) for enhancing the visualization of smaller (<25°) targeted regions in the peripheral retina. We iterated the WSAO algorithm at the speed of individual OCT B-scans (~20 ms) by using raw spectral interferograms to calculate the optimization metric. Our WSAO approach with a 3 mm beam diameter permitted primarily low- but also high- order peripheral wavefront correction in less than 10 seconds. In preliminary imaging studies in five normal human subjects, we quantified statistically significant changes with WSAO correction, corresponding to a 10.4% improvement in average pixel brightness (signal) and 7.0% improvement in high frequency content (resolution) when visualizing 1 mm (~3.5°) B-scans of the peripheral (>23°) retina. We demonstrated the ability of our WF-OCT system to acquire non wavefront-corrected wide-field images rapidly, which could then be used to locate regions of interest, zoom into targeted features, and visualize the same region at different time points. A pilot clinical study was conducted on seven healthy volunteers and two subjects with prodromal Alzheimer's disease which illustrated the capability to image Drusen-like pathologies as far as 32.5° from the fovea in un-averaged volume scans. This work suggests that the proposed combination of WF-OCT and WSAO may find applications in the diagnosis and treatment of ocular, and potentially neurodegenerative, diseases of the peripheral retina, including diabetes and Alzheimer's disease.

Wide-field retinal optical coherence tomography with wavefront sensorless adaptive optics for enhanced imaging of targeted regions

PubMed Central

Polans, James; Keller, Brenton; Carrasco-Zevallos, Oscar M.; LaRocca, Francesco; Cole, Elijah; Whitson, Heather E.; Lad, Eleonora M.; Farsiu, Sina; Izatt, Joseph A.

2016-01-01

The peripheral retina of the human eye offers a unique opportunity for assessment and monitoring of ocular diseases. We have developed a novel wide-field (>70°) optical coherence tomography system (WF-OCT) equipped with wavefront sensorless adaptive optics (WSAO) for enhancing the visualization of smaller (<25°) targeted regions in the peripheral retina. We iterated the WSAO algorithm at the speed of individual OCT B-scans (~20 ms) by using raw spectral interferograms to calculate the optimization metric. Our WSAO approach with a 3 mm beam diameter permitted primarily low- but also high- order peripheral wavefront correction in less than 10 seconds. In preliminary imaging studies in five normal human subjects, we quantified statistically significant changes with WSAO correction, corresponding to a 10.4% improvement in average pixel brightness (signal) and 7.0% improvement in high frequency content (resolution) when visualizing 1 mm (~3.5°) B-scans of the peripheral (>23°) retina. We demonstrated the ability of our WF-OCT system to acquire non wavefront-corrected wide-field images rapidly, which could then be used to locate regions of interest, zoom into targeted features, and visualize the same region at different time points. A pilot clinical study was conducted on seven healthy volunteers and two subjects with prodromal Alzheimer’s disease which illustrated the capability to image Drusen-like pathologies as far as 32.5° from the fovea in un-averaged volume scans. This work suggests that the proposed combination of WF-OCT and WSAO may find applications in the diagnosis and treatment of ocular, and potentially neurodegenerative, diseases of the peripheral retina, including diabetes and Alzheimer’s disease. PMID:28101398

Genetically-Adjusted PSA Values May Prevent Delayed Biopsies in African-American Men

PubMed Central

Donin, Nicholas; Loeb, Stacy; Cooper, Phillip R.; Roehl, Kimberly A.; Baumann, Nikola A.; J.Catalona, William; Helfand, Brian T.

2014-01-01

Purpose Genetic variants called PSA-single nucleotide polymorphisms (PSA-SNPs) have been associated with serum PSA levels. We previously demonstrated that genetic correction of serum PSA in Caucasian men could reduce both potentially unnecessary biopsies by 15% to 20% and potentially delayed biopsies by 3%. Our objective was to evaluate whether genetic correction with the PSA-SNPs could reduce potentially unnecessary and/or delayed biopsies in African-American (AA) men. Materials and Methods We compared the genotypes of 4 PSA-SNPs between 964 Caucasian and 363 AA men without known PC. We adjusted PSA values based upon an individual's PSA-SNP carrier status, and calculated the percentage of men that would meet commonly used PSA thresholds for biopsy (≥2.5 or ≥4.0ng/mL) before and after genetic correction. Potentially unnecessary and delayed biopsies were defined as those men who went below and above the biopsy threshold after genetic correction, respectively. Results Overall, 349 (96.1%) and 354 (97.5%) AA men had measured PSA levels <2.5 and <4.0 ng/mL. Genetic correction in AA men did not avoid any potentially unnecessary biopsies, but resulted in a significant (p<0.001) reduction in potentially delayed biopsies by 2.5% and 3.9% based upon the biopsy threshold cutoff. Conclusions There are significant differences in the influence of the PSA-SNPs between AA and Caucasian men without known PC, as genetic correction resulted in an increased proportion of AA men crossing the threshold for biopsy. These results raise the question whether genetic differences in PSA might contribute to delayed PC diagnosis in AA patients. PMID:24712975

DRIFT COMPENSATED DIRECT COUPLED AMPLIFIER

DOEpatents

Windsor, A.A.

1959-05-01

An improved direct-coupled amplifier having zerolevel drift correction is described. The need for an auxiliary corrective-potential amplifier is eliminated thereby giving protection against overload saturation of the zero- level drift correcting circuit. (T.R.H.)

Peteye detection and correction

NASA Astrophysics Data System (ADS)

Yen, Jonathan; Luo, Huitao; Tretter, Daniel

2007-01-01

Redeyes are caused by the camera flash light reflecting off the retina. Peteyes refer to similar artifacts in the eyes of other mammals caused by camera flash. In this paper we present a peteye removal algorithm for detecting and correcting peteye artifacts in digital images. Peteye removal for animals is significantly more difficult than redeye removal for humans, because peteyes can be any of a variety of colors, and human face detection cannot be used to localize the animal eyes. In many animals, including dogs and cats, the retina has a special reflective layer that can cause a variety of peteye colors, depending on the animal's breed, age, or fur color, etc. This makes the peteye correction more challenging. We have developed a semi-automatic algorithm for peteye removal that can detect peteyes based on the cursor position provided by the user and correct them by neutralizing the colors with glare reduction and glint retention.

Application of Zernike polynomials towards accelerated adaptive focusing of transcranial high intensity focused ultrasound.

PubMed

Kaye, Elena A; Hertzberg, Yoni; Marx, Michael; Werner, Beat; Navon, Gil; Levoy, Marc; Pauly, Kim Butts

2012-10-01

To study the phase aberrations produced by human skulls during transcranial magnetic resonance imaging guided focused ultrasound surgery (MRgFUS), to demonstrate the potential of Zernike polynomials (ZPs) to accelerate the adaptive focusing process, and to investigate the benefits of using phase corrections obtained in previous studies to provide the initial guess for correction of a new data set. The five phase aberration data sets, analyzed here, were calculated based on preoperative computerized tomography (CT) images of the head obtained during previous transcranial MRgFUS treatments performed using a clinical prototype hemispherical transducer. The noniterative adaptive focusing algorithm [Larrat et al., "MR-guided adaptive focusing of ultrasound," IEEE Trans. Ultrason. Ferroelectr. Freq. Control 57(8), 1734-1747 (2010)] was modified by replacing Hadamard encoding with Zernike encoding. The algorithm was tested in simulations to correct the patients' phase aberrations. MR acoustic radiation force imaging (MR-ARFI) was used to visualize the effect of the phase aberration correction on the focusing of a hemispherical transducer. In addition, two methods for constructing initial phase correction estimate based on previous patient's data were investigated. The benefits of the initial estimates in the Zernike-based algorithm were analyzed by measuring their effect on the ultrasound intensity at the focus and on the number of ZP modes necessary to achieve 90% of the intensity of the nonaberrated case. Covariance of the pairs of the phase aberrations data sets showed high correlation between aberration data of several patients and suggested that subgroups can be based on level of correlation. Simulation of the Zernike-based algorithm demonstrated the overall greater correction effectiveness of the low modes of ZPs. The focal intensity achieves 90% of nonaberrated intensity using fewer than 170 modes of ZPs. The initial estimates based on using the average of the phase aberration data from the individual subgroups of subjects was shown to increase the intensity at the focal spot for the five subjects. The application of ZPs to phase aberration correction was shown to be beneficial for adaptive focusing of transcranial ultrasound. The skull-based phase aberrations were found to be well approximated by the number of ZP modes representing only a fraction of the number of elements in the hemispherical transducer. Implementing the initial phase aberration estimate together with Zernike-based algorithm can be used to improve the robustness and can potentially greatly increase the viability of MR-ARFI-based focusing for a clinical transcranial MRgFUS therapy.

Application of Zernike polynomials towards accelerated adaptive focusing of transcranial high intensity focused ultrasound

PubMed Central

Kaye, Elena A.; Hertzberg, Yoni; Marx, Michael; Werner, Beat; Navon, Gil; Levoy, Marc; Pauly, Kim Butts

2012-01-01

Purpose: To study the phase aberrations produced by human skulls during transcranial magnetic resonance imaging guided focused ultrasound surgery (MRgFUS), to demonstrate the potential of Zernike polynomials (ZPs) to accelerate the adaptive focusing process, and to investigate the benefits of using phase corrections obtained in previous studies to provide the initial guess for correction of a new data set. Methods: The five phase aberration data sets, analyzed here, were calculated based on preoperative computerized tomography (CT) images of the head obtained during previous transcranial MRgFUS treatments performed using a clinical prototype hemispherical transducer. The noniterative adaptive focusing algorithm [Larrat , “MR-guided adaptive focusing of ultrasound,” IEEE Trans. Ultrason. Ferroelectr. Freq. Control 57(8), 1734–1747 (2010)]10.1109/TUFFC.2010.1612 was modified by replacing Hadamard encoding with Zernike encoding. The algorithm was tested in simulations to correct the patients’ phase aberrations. MR acoustic radiation force imaging (MR-ARFI) was used to visualize the effect of the phase aberration correction on the focusing of a hemispherical transducer. In addition, two methods for constructing initial phase correction estimate based on previous patient's data were investigated. The benefits of the initial estimates in the Zernike-based algorithm were analyzed by measuring their effect on the ultrasound intensity at the focus and on the number of ZP modes necessary to achieve 90% of the intensity of the nonaberrated case. Results: Covariance of the pairs of the phase aberrations data sets showed high correlation between aberration data of several patients and suggested that subgroups can be based on level of correlation. Simulation of the Zernike-based algorithm demonstrated the overall greater correction effectiveness of the low modes of ZPs. The focal intensity achieves 90% of nonaberrated intensity using fewer than 170 modes of ZPs. The initial estimates based on using the average of the phase aberration data from the individual subgroups of subjects was shown to increase the intensity at the focal spot for the five subjects. Conclusions: The application of ZPs to phase aberration correction was shown to be beneficial for adaptive focusing of transcranial ultrasound. The skull-based phase aberrations were found to be well approximated by the number of ZP modes representing only a fraction of the number of elements in the hemispherical transducer. Implementing the initial phase aberration estimate together with Zernike-based algorithm can be used to improve the robustness and can potentially greatly increase the viability of MR-ARFI-based focusing for a clinical transcranial MRgFUS therapy. PMID:23039661

75 FR 34488 - National Endowment for the Arts; National Council on the Arts 170th Meeting; Correction

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-17

... NATIONAL FOUNDATION ON THE ARTS AND THE HUMANITIES National Endowment for the Arts; National Council on the Arts 170th Meeting; Correction This notice is to correct the previously announced dates of the meeting of the National Council on the Arts. The meeting will be held on June 24-25, 2010 not June...

Correction techniques for depth errors with stereo three-dimensional graphic displays

NASA Technical Reports Server (NTRS)

Parrish, Russell V.; Holden, Anthony; Williams, Steven P.

1992-01-01

Three-dimensional (3-D), 'real-world' pictorial displays that incorporate 'true' depth cues via stereopsis techniques have proved effective for displaying complex information in a natural way to enhance situational awareness and to improve pilot/vehicle performance. In such displays, the display designer must map the depths in the real world to the depths available with the stereo display system. However, empirical data have shown that the human subject does not perceive the information at exactly the depth at which it is mathematically placed. Head movements can also seriously distort the depth information that is embedded in stereo 3-D displays because the transformations used in mapping the visual scene to the depth-viewing volume (DVV) depend intrinsically on the viewer location. The goal of this research was to provide two correction techniques; the first technique corrects the original visual scene to the DVV mapping based on human perception errors, and the second (which is based on head-positioning sensor input data) corrects for errors induced by head movements. Empirical data are presented to validate both correction techniques. A combination of the two correction techniques effectively eliminates the distortions of depth information embedded in stereo 3-D displays.

Simulating the impact of climate, land use and human water use on the hydrological system over the period 1850-2100 using PCR-GLOBWB

NASA Astrophysics Data System (ADS)

Bosmans, Joyce; van Beek, Rens; Bierkens, Marc

2015-04-01

In this study we investigate the impact of humans on the global hydrological system by separating the impacts of climate change, land use and land cover change, and human water use in a series of experiments with the PCR-GLOBWB hydrological model (e.g. van Beek et al., 2011; Sutanudjaja et al., 2014). We force PCR-GLOBWB with input from the EC-Earth and CESM GCMs, allowing us to extend our experiments from the pre-industrial (1850) to the end of the century (2099). Two greenhouse gas emission scenarios are used for the coming century: Representative Concentration Pathway 2.6 (RCP2.6), a low-end scenario, as well as the high-end RCP8.5 scenario. Precipitation, temperature and reference potential evapotranspiration are applied to PCR-GLOBWB, after bias-correction using the ISI-MIP method (Hempel et al., 2013). The reference potential evapotranspiration is computed using the Penman-Monteith equation with GCM wind, radiation, temperature, humidity and pressure as opposed to the Hamon method used as default in PCR-GLOBWB. To evaluate the impacts of climate change as well as land use and land cover (LULC) change, we apply a combination of fixed and transient LULC scenarios. First, LULC is kept fixed at 1850 values, so the hydrological model is only experiencing changes in precipitation, temperature and reference potential evapotranspiration. Then, LULC is allowed to vary according to historical reconstructions (HYDE) and future projections per RCP (Hurtt et al., 2011). In these experiments, anthropogenic effects are excluded. This is the first study to evaluate PCR-GLOBWB with pre-industrial or transient LULC in combination with present and future climate change. The next step is to investigate human impacts on the water system, by comparing the experiment with varying LULC to an experiment that additionally includes reservoir operations, human water abstractions including irrigation (paddy and non-paddy) and subsequent return flows. We aim to project future human impacts using information based on Shared Socioeconomic Pathways (SSPs). In previous studies, domestic, industrial and irrigation water demand were varied over the past decades in PCR-GLOBWB. Here we improve the analyses of human impacts on the hydrological system by looking further into the past and the future, as well as by comparing the impact of human water use to impacts of climate and LULC change. van Beek et al (2011), Global monthly water stress: 1. Water balance and water availability. Water Resources Research, Vol 47. Hempel et al (2013), A trend-preserving bias correction - the ISI-MIP approach. Earth System Dynamics, Vol 4. Hurtt et al (2011), Harmonization of land-use scenarios for the period 1500-2100: 600 years of global gridded annual land-use transitions, wood harvest, and resulting secondary lands. Climatic Change, Vol 109. Sutanudjaja et al (2014), Development and validation of PCR-GLOBWB 2.0: a 5 arc min resolution global hydrology and water resources model. EGU General Assembly Conference Abstracts

Low-energy effective action in two-dimensional SQED: a two-loop analysis

NASA Astrophysics Data System (ADS)

Samsonov, I. B.

2017-07-01

We study two-loop quantum corrections to the low-energy effective actions in N=(2,2) and N=(4,4) SQED on the Coulomb branch. In the latter model, the low-energy effective action is described by a generalized Kähler potential which depends on both chiral and twisted chiral superfields. We demonstrate that this generalized Kähler potential is one-loop exact and corresponds to the N=(4,4) sigma-model with torsion presented by Roček, Schoutens and Sevrin [1]. In the N=(2,2) SQED, the effective Kähler potential is not protected against higher-loop quantum corrections. The two-loop quantum corrections to this potential and the corresponding sigma-model metric are explicitly found.

Quantum corrections to newtonian potential and generalized uncertainty principle

NASA Astrophysics Data System (ADS)

Scardigli, Fabio; Lambiase, Gaetano; Vagenas, Elias

2017-08-01

We use the leading quantum corrections to the newtonian potential to compute the deformation parameter of the generalized uncertainty principle. By assuming just only General Relativity as theory of Gravitation, and the thermal nature of the GUP corrections to the Hawking spectrum, our calculation gives, to first order, a specific numerical result. We briefly discuss the physical meaning of this value, and compare it with the previously obtained bounds on the generalized uncertainty principle deformation parameter.

Impulsive correction to the elastic moduli obtained using the stress-fluctuation formalism in systems with truncated pair potential

NASA Astrophysics Data System (ADS)

Xu, H.; Wittmer, J. P.; Polińska, P.; Baschnagel, J.

2012-10-01

The truncation of a pair potential at a distance rc is well known to imply, in general, an impulsive correction to the pressure and other moments of the first derivatives of the potential. That, depending on rc, the truncation may also be of relevance to higher derivatives is shown theoretically for the Born contributions to the elastic moduli obtained using the stress-fluctuation formalism in d dimensions. Focusing on isotropic liquids for which the shear modulus G must vanish by construction, the predicted corrections are tested numerically for binary mixtures and polydisperse Lennard-Jones beads in, respectively, d=3 and 2 dimensions. Both models being glass formers, we comment briefly on the temperature (T) dependence of the (corrected) shear modulus G(T) around the glass transition temperature Tg.

Experimental demonstration of passive acoustic imaging in the human skull cavity using CT-based aberration corrections.

PubMed

Jones, Ryan M; O'Reilly, Meaghan A; Hynynen, Kullervo

2015-07-01

Experimentally verify a previously described technique for performing passive acoustic imaging through an intact human skull using noninvasive, computed tomography (CT)-based aberration corrections Jones et al. [Phys. Med. Biol. 58, 4981-5005 (2013)]. A sparse hemispherical receiver array (30 cm diameter) consisting of 128 piezoceramic discs (2.5 mm diameter, 612 kHz center frequency) was used to passively listen through ex vivo human skullcaps (n = 4) to acoustic emissions from a narrow-band fixed source (1 mm diameter, 516 kHz center frequency) and from ultrasound-stimulated (5 cycle bursts, 1 Hz pulse repetition frequency, estimated in situ peak negative pressure 0.11-0.33 MPa, 306 kHz driving frequency) Definity™ microbubbles flowing through a thin-walled tube phantom. Initial in vivo feasibility testing of the method was performed. The performance of the method was assessed through comparisons to images generated without skull corrections, with invasive source-based corrections, and with water-path control images. For source locations at least 25 mm from the inner skull surface, the modified reconstruction algorithm successfully restored a single focus within the skull cavity at a location within 1.25 mm from the true position of the narrow-band source. The results obtained from imaging single bubbles are in good agreement with numerical simulations of point source emitters and the authors' previous experimental measurements using source-based skull corrections O'Reilly et al. [IEEE Trans. Biomed. Eng. 61, 1285-1294 (2014)]. In a rat model, microbubble activity was mapped through an intact human skull at pressure levels below and above the threshold for focused ultrasound-induced blood-brain barrier opening. During bursts that led to coherent bubble activity, the location of maximum intensity in images generated with CT-based skull corrections was found to deviate by less than 1 mm, on average, from the position obtained using source-based corrections. Taken together, these results demonstrate the feasibility of using the method to guide bubble-mediated ultrasound therapies in the brain. The technique may also have application in ultrasound-based cerebral angiography.

Experimental demonstration of passive acoustic imaging in the human skull cavity using CT-based aberration corrections

PubMed Central

Jones, Ryan M.; O’Reilly, Meaghan A.; Hynynen, Kullervo

2015-01-01

Purpose: Experimentally verify a previously described technique for performing passive acoustic imaging through an intact human skull using noninvasive, computed tomography (CT)-based aberration corrections Jones et al. [Phys. Med. Biol. 58, 4981–5005 (2013)]. Methods: A sparse hemispherical receiver array (30 cm diameter) consisting of 128 piezoceramic discs (2.5 mm diameter, 612 kHz center frequency) was used to passively listen through ex vivo human skullcaps (n = 4) to acoustic emissions from a narrow-band fixed source (1 mm diameter, 516 kHz center frequency) and from ultrasound-stimulated (5 cycle bursts, 1 Hz pulse repetition frequency, estimated in situ peak negative pressure 0.11–0.33 MPa, 306 kHz driving frequency) Definity™ microbubbles flowing through a thin-walled tube phantom. Initial in vivo feasibility testing of the method was performed. The performance of the method was assessed through comparisons to images generated without skull corrections, with invasive source-based corrections, and with water-path control images. Results: For source locations at least 25 mm from the inner skull surface, the modified reconstruction algorithm successfully restored a single focus within the skull cavity at a location within 1.25 mm from the true position of the narrow-band source. The results obtained from imaging single bubbles are in good agreement with numerical simulations of point source emitters and the authors’ previous experimental measurements using source-based skull corrections O’Reilly et al. [IEEE Trans. Biomed. Eng. 61, 1285–1294 (2014)]. In a rat model, microbubble activity was mapped through an intact human skull at pressure levels below and above the threshold for focused ultrasound-induced blood–brain barrier opening. During bursts that led to coherent bubble activity, the location of maximum intensity in images generated with CT-based skull corrections was found to deviate by less than 1 mm, on average, from the position obtained using source-based corrections. Conclusions: Taken together, these results demonstrate the feasibility of using the method to guide bubble-mediated ultrasound therapies in the brain. The technique may also have application in ultrasound-based cerebral angiography. PMID:26133635

Role of shell corrections in the phenomenon of cluster radioactivity

NASA Astrophysics Data System (ADS)

Kaur, Mandeep; Singh, Bir Bikram; Sharma, Manoj K.

2018-05-01

The detailed investigation has been carried out to explore the role of shell corrections in the decay of various radioactive parent nuclei in trans-lead region, specifically, which lead to doubly magic 208Pb daughter nucleus through emission of clusters such as 14C, 18,20O, 22,24,26Ne, 28,30 Mg and 34S i. The fragmentation potential comprises of binding energies (BE), Coulomb potential (Vc) and nuclear or proximity potential (VP) of the decaying fragments (or clusters). It is relevant to mention here that the contributions of VLDM (T=0) and δU (T=0) in the BE have been analysed within the Strutinsky renormanlization procedure. In the framework of quantum mechanical fragmentation theory (QMFT), we have investigated the above mentioned cluster decays with and without inclusion of shell corrections in the fragmentation potential for spherical as well as non-compact oriented nuclei. We find that the experimentally observed clusters 14C, 18,20O, 22,24,26 Ne, 28,30 Mg and 34Si having doubly magic 208 Pb daughter nucleus are not strongly minimized, they do so only after the inclusion of shell corrections in the fragmentation potential. The nuclear structure information carried by the shell corrections have been explored via these calculations, within the collective clusterisation process of QMFT, in the study of ground state decay of radioactive nuclei. The role of different parts of fragmentation potentials such as VLDM, δU, Vc and Vp is dually analysed for better understanding of radioactive cluster decay.

Motivating drivers to correctly adjust head restraints: assessing effectiveness of three different interventions.

PubMed

Fockler, S K; Vavrik, J; Kristiansen, L

1998-11-01

Three types of driver educational strategies were tested to determine the most effective approach for motivating drivers to adjust their head restraints to the correct vertical position: (1) a human interactive personal contact with a member of an ICBC-trained head restraint adjustment team, (2) a passive video presentation of the consequences of correct and incorrect head restraint adjustment, and (3) an interactive three-dimensional kinetic model showing the consequences of correct and incorrect head restraint adjustment. An experimental pretest-posttest control group design was used. A different educational treatment was used in each of three lanes of a vehicle emissions testing facility, with a fourth lane with no intervention serving as a control group. Observational and self-reported data were obtained from a total of 1,974 vehicles entering and exiting the facility. The human intervention led to significantly more drivers actually adjusting their head restraints immediately after the intervention than the passive video or interactive kinetic model approaches, which were both no different from the control group. The human intervention was recommended as the most effective and was implemented successfully on a limited basis during 3 months of 1995 and again during 3 months of 1996.

Characterization and Operation of Liquid Crystal Adaptive Optics Phoropter

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

Awwal, A; Bauman, B; Gavel, D

2003-02-05

Adaptive optics (AO), a mature technology developed for astronomy to compensate for the effects of atmospheric turbulence, can also be used to correct the aberrations of the eye. The classic phoropter is used by ophthalmologists and optometrists to estimate and correct the lower-order aberrations of the eye, defocus and astigmatism, in order to derive a vision correction prescription for their patients. An adaptive optics phoropter measures and corrects the aberrations in the human eye using adaptive optics techniques, which are capable of dealing with both the standard low-order aberrations and higher-order aberrations, including coma and spherical aberration. High-order aberrations havemore » been shown to degrade visual performance for clinical subjects in initial investigations. An adaptive optics phoropter has been designed and constructed based on a Shack-Hartmann sensor to measure the aberrations of the eye, and a liquid crystal spatial light modulator to compensate for them. This system should produce near diffraction-limited optical image quality at the retina, which will enable investigation of the psychophysical limits of human vision. This paper describes the characterization and operation of the AO phoropter with results from human subject testing.« less

Preclinical Corrective Gene Transfer in Xeroderma Pigmentosum Human Skin Stem Cells

PubMed Central

Warrick, Emilie; Garcia, Marta; Chagnoleau, Corinne; Chevallier, Odile; Bergoglio, Valérie; Sartori, Daniela; Mavilio, Fulvio; Angulo, Jaime F; Avril, Marie-Françoise; Sarasin, Alain; Larcher, Fernando; Del Rio, Marcela; Bernerd, Françoise; Magnaldo, Thierry

2012-01-01

Xeroderma pigmentosum (XP) is a devastating disease associated with dramatic skin cancer proneness. XP cells are deficient in nucleotide excision repair (NER) of bulky DNA adducts including ultraviolet (UV)-induced mutagenic lesions. Approaches of corrective gene transfer in NER-deficient keratinocyte stem cells hold great hope for the long-term treatment of XP patients. To face this challenge, we developed a retrovirus-based strategy to safely transduce the wild-type XPC gene into clonogenic human primary XP-C keratinocytes. De novo expression of XPC was maintained in both mass population and derived independent candidate stem cells (holoclones) after more than 130 population doublings (PD) in culture upon serial propagation (>1040 cells). Analyses of retrovirus integration sequences in isolated keratinocyte stem cells suggested the absence of adverse effects such as oncogenic activation or clonal expansion. Furthermore, corrected XP-C keratinocytes exhibited full NER capacity as well as normal features of epidermal differentiation in both organotypic skin cultures and in a preclinical murine model of human skin regeneration in vivo. The achievement of a long-term genetic correction of XP-C epidermal stem cells constitutes the first preclinical model of ex vivo gene therapy for XP-C patients. PMID:22068429

76 FR 48874 - Notice of Meetings; Correction

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-09

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Substance Abuse and Mental Health Services Administration Notice of Meetings; Correction The Substance Abuse and Mental Health Services Administration published a... the Substance Abuse and Mental Health Services Administration's (SAMHSA) four National Advisory...

78 FR 14806 - Health Resources and Services Administration

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-07

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Health Resources and Services Administration Statement of Organization, Functions and Delegations of Authority; Correction AGENCY: Health Resources and Services Administration (HRSA), HHS. ACTION: Notice; correction. SUMMARY: HRSA published a document in the Federal...

76 FR 55068 - Mobile Medical Applications Draft Guidance; Public Workshop; Correction

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-06

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0530] Mobile Medical Applications Draft Guidance; Public Workshop; Correction AGENCY: Food and Drug... announced a public workshop entitled ``Mobile [[Page 55069

DOUBLE TRACKS Test Site interim corrective action plan

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

NONE

The DOUBLE TRACKS site is located on Range 71 north of the Nellis Air Force Range, northwest of the Nevada Test Site (NTS). DOUBLE TRACKS was the first of four experiments that constituted Operation ROLLER COASTER. On May 15, 1963, weapons-grade plutonium and depleted uranium were dispersed using 54 kilograms of trinitrotoluene (TNT) explosive. The explosion occurred in the open, 0.3 m above the steel plate. No fission yield was detected from the test, and the total amount of plutonium deposited on the ground surface was estimated to be between 980 and 1,600 grams. The test device was composed primarilymore » of uranium-238 and plutonium-239. The mass ratio of uranium to plutonium was 4.35. The objective of the corrective action is to reduce the potential risk to human health and the environment and to demonstrate technically viable and cost-effective excavation, transportation, and disposal. To achieve these objectives, Bechtel Nevada (BN) will remove soil with a total transuranic activity greater then 200 pCI/g, containerize the soil in ``supersacks,`` transport the filled ``supersacks`` to the NTS, and dispose of them in the Area 3 Radioactive Waste Management Site. During this interim corrective action, BN will also conduct a limited demonstration of an alternative method for excavation of radioactive near-surface soil contamination.« less

Gene Editing and Genetic Lung Disease. Basic Research Meets Therapeutic Application.

PubMed

Alapati, Deepthi; Morrisey, Edward E

2017-03-01

Although our understanding of the genetics and pathology of congenital lung diseases such as surfactant protein deficiency, cystic fibrosis, and alpha-1 antitrypsin deficiency is extensive, treatment options are lacking. Because the lung is a barrier organ in direct communication with the external environment, targeted delivery of gene corrective technologies to the respiratory system via intratracheal or intranasal routes is an attractive option for therapy. CRISPR/Cas9 gene-editing technology is a promising approach to repairing or inactivating disease-causing mutations. Recent reports have provided proof of concept by using CRISPR/Cas9 to successfully repair or inactivate mutations in animal models of monogenic human diseases. Potential pulmonary applications of CRISPR/Cas9 gene editing include gene correction of monogenic diseases in pre- or postnatal lungs and ex vivo gene editing of patient-specific airway stem cells followed by autologous cell transplant. Strategies to enhance gene-editing efficiency and eliminate off-target effects by targeting pulmonary stem/progenitor cells and the assessment of short-term and long-term effects of gene editing are important considerations as the field advances. If methods continue to advance rapidly, CRISPR/Cas9-mediated gene editing may provide a novel opportunity to correct monogenic diseases of the respiratory system.

Phospholipids in Human Milk and Infant Formulas: Benefits and Needs for Correct Infant Nutrition.

PubMed

Cilla, Antonio; Diego Quintaes, Késia; Barberá, Reyes; Alegría, Amparo

2016-08-17

The composition of human milk has served as a basis for the development of infant formulas, which are used when breastfeeding is not possible. Among the human milk nutrients, 50% of the total energetic value corresponds to fat, with a high level of fatty acids and 0.2-2.0% present in the form of phospholipids (PLs). The PL contents and fatty acid distribution in PL species have been investigated as bioactive elements for the production of infant formulas, since they offer potential benefits for the optimum growth and health of the newborn infant. The differences in the amount of PLs and in fatty acid distribution in PL species between human milk and infant formulas can imply biologically significant differences for newborn infants fed with infant formulas versus human milk-mainly due to the greater proportion of sphingomyelin with respect to phosphatidylcholine in infant formulas. The limited information referred to the characterization of fatty acid distribution in PL species in infant formulas or in ingredients used to enrich them merits further research in order to obtain products with benefits similar to those of human milk in terms of infant growth, visual acuity, and neurological development. The present review establishes the scientific basis for helping to adjust formulations to the requirements of infant nutrition.

Function of MYO7A in the Human RPE and the Validity of Shaker1 Mice as a Model for Usher Syndrome 1B

PubMed Central

Gibbs, Daniel; Diemer, Tanja; Khanobdee, Kornnika; Hu, Jane; Bok, Dean

2010-01-01

Purpose. To investigate the function of MYO7A in human RPE cells and to test the validity of using shaker1 RPE in preclinical studies on therapies for Usher syndrome 1B by comparing human and mouse cells. Methods. MYO7A was localized by immunofluorescence. Primary cultures of human and mouse RPE cells were used to measure melanosome motility and rod outer segment (ROS) phagocytosis and digestion. MYO7A was knocked down in the human RPE cells by RNAi to test for a mutant phenotype in melanosome motility. Results. The distribution of MYO7A in the RPE of human and mouse was found to be comparable, both in vivo and in primary cultures. Primary cultures of human RPE cells phagocytosed and digested ROSs with kinetics comparable to that of primary cultures of mouse RPE cells. Melanosome motility was also comparable, and, after RNAi knockdown, consisted of longer-range fast movements characteristic of melanosomes in shaker1 RPE. Conclusions. The localization and function of MYO7A in human RPE cells is comparable to that in mouse RPE cells. Although shaker1 retinas do not undergo degeneration, correction of mutant phenotypes in the shaker1 RPE represents a valid preclinical test for potential therapeutic treatments. PMID:19643958

Effect of aberrations in human eye on contrast sensitivity function

NASA Astrophysics Data System (ADS)

Quan, Wei; Wang, Feng-lin; Wang, Zhao-qi

2011-06-01

The quantitative analysis of the effect of aberrations in human eye on vision has important clinical value in the correction of aberrations. The wave-front aberrations of human eyes were measured with the Hartmann-Shack wave-front sensor and modulation transfer function (MTF) was computed from the wave-front aberrations. Contrast sensitivity function (CSF) was obtained from MTF and the retinal aerial image modulation (AIM). It is shown that the 2nd, 3rd, 4th, 5th, 6th Zernike aberrations deteriorate contrast sensitivity function. When the 2nd, 3rd, 4th, 5th, 6th Zernike aberrations are corrected high contrast sensitivity function can be obtained.

Caffeine affects the biological responses of human hematopoietic cells of myeloid lineage via downregulation of the mTOR pathway and xanthine oxidase activity

PubMed Central

Abooali, Maryam; Yasinska, Inna M.; Casely-Hayford, Maxwell A.; Berger, Steffen M.; Fasler-Kan, Elizaveta; Sumbayev, Vadim V.

2015-01-01

Correction of human myeloid cell function is crucial for the prevention of inflammatory and allergic reactions as well as leukaemia progression. Caffeine, a naturally occurring food component, is known to display anti-inflammatory effects which have previously been ascribed largely to its inhibitory actions on phosphodiesterase. However, more recent studies suggest an additional role in affecting the activity of the mammalian target of rapamycin (mTOR), a master regulator of myeloid cell translational pathways, although detailed molecular events underlying its mode of action have not been elucidated. Here, we report the cellular uptake of caffeine, without metabolisation, by healthy and malignant hematopoietic myeloid cells including monocytes, basophils and primary acute myeloid leukaemia mononuclear blasts. Unmodified caffeine downregulated mTOR signalling, which affected glycolysis and the release of pro-inflammatory/pro-angiogenic cytokines as well as other inflammatory mediators. In monocytes, the effects of caffeine were potentiated by its ability to inhibit xanthine oxidase, an enzyme which plays a central role in human purine catabolism by generating uric acid. In basophils, caffeine also increased intracellular cyclic adenosine monophosphate (cAMP) levels which further enhanced its inhibitory action on mTOR. These results demonstrate an important mode of pharmacological action of caffeine with potentially wide-ranging therapeutic impact for treating non-infectious disorders of the human immune system, where it could be applied directly to inflammatory cells. PMID:26384306

Error-Induced Learning as a Resource-Adaptive Process in Young and Elderly Individuals

NASA Astrophysics Data System (ADS)

Ferdinand, Nicola K.; Weiten, Anja; Mecklinger, Axel; Kray, Jutta

Thorndike described in his law of effect [44] that actions followed by positive events are more likely to be repeated in the future, whereas actions that are followed by negative outcomes are less likely to be repeated. This implies that behavior is evaluated in the light of its potential consequences, and non-reward events (i.e., errors) must be detected for reinforcement learning to take place. In short, humans have to monitor their performance in order to detect and correct errors, and this allows them to successfully adapt their behavior to changing environmental demands and acquire new behavior, i.e., to learn.

Full genome sequence of Rocio virus reveal substantial variations from the prototype Rocio virus SPH 34675 sequence.

PubMed

Setoh, Yin Xiang; Amarilla, Alberto A; Peng, Nias Y; Slonchak, Andrii; Periasamy, Parthiban; Figueiredo, Luiz T M; Aquino, Victor H; Khromykh, Alexander A

2018-01-01

Rocio virus (ROCV) is an arbovirus belonging to the genus Flavivirus, family Flaviviridae. We present an updated sequence of ROCV strain SPH 34675 (GenBank: AY632542.4), the only available full genome sequence prior to this study. Using next-generation sequencing of the entire genome, we reveal substantial sequence variation from the prototype sequence, with 30 nucleotide differences amounting to 14 amino acid changes, as well as significant changes to predicted 3'UTR RNA structures. Our results present an updated and corrected sequence of a potential emerging human-virulent flavivirus uniquely indigenous to Brazil (GenBank: MF461639).

GUP parameter from quantum corrections to the Newtonian potential

NASA Astrophysics Data System (ADS)

Scardigli, Fabio; Lambiase, Gaetano; Vagenas, Elias C.

2017-04-01

We propose a technique to compute the deformation parameter of the generalized uncertainty principle by using the leading quantum corrections to the Newtonian potential. We just assume General Relativity as theory of Gravitation, and the thermal nature of the GUP corrections to the Hawking spectrum. With these minimal assumptions our calculation gives, to first order, a specific numerical result. The physical meaning of this value is discussed, and compared with the previously obtained bounds on the generalized uncertainty principle deformation parameter.

The effect of anterior longitudinal ligament resection on lordosis correction during minimally invasive lateral lumbar interbody fusion: Biomechanical and radiographic feasibility of an integrated spacer/plate interbody reconstruction device.

PubMed

Kim, Choll; Harris, Jonathan A; Muzumdar, Aditya; Khalil, Saif; Sclafani, Joseph A; Raiszadeh, Kamshad; Bucklen, Brandon S

2017-03-01

Lateral lumbar interbody fusion is powerful for correcting degenerative conditions, yet sagittal correction remains limited by anterior longitudinal ligament tethering. Although lordosis has been restored via ligament release, biomechanical consequences remain unknown. Investigators examined radiographic and biomechanical of ligament release for restoration of lumbar lordosis. Six fresh-frozen human cadaveric spines (L3-S1) were tested: (Miller et al., 1988) intact; (Battie et al., 1995) 8mm spacer with intact anterior longitudinal ligament; (Cho et al., 2013) 8mm spacer without intact ligament following ligament resection; (Galbusera et al., 2013) 13mm lateral lumbar interbody fusion; (Goldstein et al., 2001) integrated 13mm spacer. Focal lordosis and range of motion were assessed by applying pure moments in flexion-extension, lateral bending, and axial rotation. Cadaveric radiographs showed significant improvement in lordosis correction following ligament resection (P<0.05). The 8mm spacer with ligament construct provided greatest stability relative to intact (P>0.05) but did little to restore lordosis. Ligament release significantly destabilized the spine relative to intact in all modes and 8mm with ligament in lateral bending and axial rotation (P<0.05). Integrated lateral lumbar interbody fusion following ligament resection did not significantly differ from intact or from 8mm with ligament in all testing modes (P>0.05). Lordosis corrected by lateral lumbar interbody fusion can be improved by anterior longitudinal ligament resection, but significant construct instability and potential implant migration/dislodgment may result. This study shows that an added integrated lateral fixation system can significantly improve construct stability. Long-term multicenter studies are needed. Copyright © 2017 Elsevier Ltd. All rights reserved.

Whole-Body Biodistribution, Dosimetry, and Metabolite Correction of [11C]Palmitate: A PET Tracer for Imaging of Fatty Acid Metabolism

PubMed Central

Christensen, Nana L.; Jakobsen, Steen; Schacht, Anna C.; Munk, Ole L.; Alstrup, Aage K. O.; Tolbod, Lars P.; Harms, Hendrik J.; Nielsen, Søren

2017-01-01

Introduction: Despite the decades long use of [11C]palmitate positron emission tomography (PET)/computed tomography in basic metabolism studies, only personal communications regarding dosimetry and biodistribution data have been published. Methods: Dosimetry and biodistribution studies were performed in 2 pigs and 2 healthy volunteers by whole-body [11C]palmitate PET scans. Metabolite studies were performed in 40 participants (healthy and with type 2 diabetes) under basal and hyperinsulinemic conditions. Metabolites were estimated using 2 approaches and subsequently compared: Indirect [11C]CO2 release and parent [11C]palmitate measured by a solid-phase extraction (SPE) method. Finally, myocardial fatty acid uptake was calculated in a patient cohort using input functions derived from individual metabolite correction compared with population-based metabolite correction. Results: In humans, mean effective dose was 3.23 (0.02) µSv/MBq, with the liver and myocardium receiving the highest absorbed doses. Metabolite correction using only [11C]CO2 estimates underestimated the fraction of metabolites in studies lasting more than 20 minutes. Population-based metabolite correction showed excellent correlation with individual metabolite correction in the cardiac PET validation cohort. Conclusion: First, mean effective dose of [11C]palmitate is 3.23 (0.02) µSv/MBq in humans allowing multiple scans using ∼300 MBq [11C]palmitate, and secondly, population-based metabolite correction compares well with individual correction. PMID:29073808

Corrective Action Decision Document for Corrective Action Unit 204: Storage Bunkers, Nevada Test Site, Nevada: Revision 0, Including Errata Sheet

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

U.S. Department of Energy, National Nuclear Security Administration Nevada Site Office

2004-04-01

This Corrective Action Decision Document identifies the U.S. Department of Energy, National Nuclear Security Administration Nevada Site Office's corrective action alternative recommendation for each of the corrective action sites (CASs) within Corrective Action Unit (CAU) 204: Storage Bunkers, Nevada Test Site (NTS), Nevada, under the Federal Facility Agreement and Consent Order. An evaluation of analytical data from the corrective action investigation, review of current and future operations at each CAS, and a detailed comparative analysis of potential corrective action alternatives were used to determine the appropriate corrective action for each CAS. There are six CASs in CAU 204, which aremore » all located between Areas 1, 2, 3, and 5 on the NTS. The No Further Action alternative was recommended for CASs 01-34-01, 02-34-01, 03-34-01, and 05-99-02; and a Closure in Place with Administrative Controls recommendation was the preferred corrective action for CASs 05-18-02 and 05-33-01. These alternatives were judged to meet all requirements for the technical components evaluated as well as applicable state and federal regulations for closure of the sites and will eliminate potential future exposure pathways to the contaminated media at CAU 204.« less

Neural Dynamics Underlying Target Detection in the Human Brain

PubMed Central

Bansal, Arjun K.; Madhavan, Radhika; Agam, Yigal; Golby, Alexandra; Madsen, Joseph R.

2014-01-01

Sensory signals must be interpreted in the context of goals and tasks. To detect a target in an image, the brain compares input signals and goals to elicit the correct behavior. We examined how target detection modulates visual recognition signals by recording intracranial field potential responses from 776 electrodes in 10 epileptic human subjects. We observed reliable differences in the physiological responses to stimuli when a cued target was present versus absent. Goal-related modulation was particularly strong in the inferior temporal and fusiform gyri, two areas important for object recognition. Target modulation started after 250 ms post stimulus, considerably after the onset of visual recognition signals. While broadband signals exhibited increased or decreased power, gamma frequency power showed predominantly increases during target presence. These observations support models where task goals interact with sensory inputs via top-down signals that influence the highest echelons of visual processing after the onset of selective responses. PMID:24553944

Hair analyses: worthless for vitamins, limited for minerals.

PubMed

Hambidge, K M

1982-11-01

Despite many major and minor problems with interpretation of analytical data, chemical analyses of human hair have some potential value. Extensive research will be necessary to define this value, including correlation of hair concentrations of specific elements with those in other tissues and metabolic pools and definition of normal physiological concentration ranges. Many factors that may compromise the correct interpretation of analytical data require detailed evaluation for each specific element. Meanwhile, hair analyses are of some value in the comparison of different populations and, for example, in public health community surveys of environmental exposure to heavy metals. On an individual basis, their established usefulness is much more restricted and the limitations are especially notable for evaluation of mineral nutritional status. There is a wide gulf between the limited and mainly tentative scientific justification for their use on an individual basis and the current exploitation of multielement chemical analyses of human hair.

Sensitivity-Enhanced Wearable Active Voiceprint Sensor Based on Cellular Polypropylene Piezoelectret.

PubMed

Li, Wenbo; Zhao, Sheng; Wu, Nan; Zhong, Junwen; Wang, Bo; Lin, Shizhe; Chen, Shuwen; Yuan, Fang; Jiang, Hulin; Xiao, Yongjun; Hu, Bin; Zhou, Jun

2017-07-19

Wearable active sensors have extensive applications in mobile biosensing and human-machine interaction but require good flexibility, high sensitivity, excellent stability, and self-powered feature. In this work, cellular polypropylene (PP) piezoelectret was chosen as the core material of a sensitivity-enhanced wearable active voiceprint sensor (SWAVS) to realize voiceprint recognition. By virtue of the dipole orientation control method, the air layers in the piezoelectret were efficiently utilized, and the current sensitivity was enhanced (from 1.98 pA/Hz to 5.81 pA/Hz at 115 dB). The SWAVS exhibited the superiorities of high sensitivity, accurate frequency response, and excellent stability. The voiceprint recognition system could make correct reactions to human voices by judging both the password and speaker. This study presented a voiceprint sensor with potential applications in noncontact biometric recognition and safety guarantee systems, promoting the progress of wearable sensor networks.

Training Correctional Educators: A Needs Assessment Study.

ERIC Educational Resources Information Center

Jurich, Sonia; Casper, Marta; Hull, Kim A.

2001-01-01

Focus groups and a training needs survey of Virginia correctional educators identified educational philosophy, communication skills, human behavior, and teaching techniques as topics of interest. Classroom observations identified additional areas: teacher isolation, multiple challenges, absence of grade structure, and safety constraints. (Contains…

78 FR 17155 - Standards for the Growing, Harvesting, Packing, and Holding of Produce for Human Consumption...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-20

...The Food and Drug Administration (FDA or we) is correcting the preamble to a proposed rule that published in the Federal Register of January 16, 2013. That proposed rule would establish science-based minimum standards for the safe growing, harvesting, packing, and holding of produce, meaning fruits and vegetables grown for human consumption. FDA proposed these standards as part of our implementation of the FDA Food Safety Modernization Act. The document published with several technical errors, including some errors in cross references, as well as several errors in reference numbers cited throughout the document. This document corrects those errors. We are also placing a corrected copy of the proposed rule in the docket.

Elimination of Spurious Fractional Charges in Dissociating Molecules by Correcting the Shape of Approximate Kohn-Sham Potentials.

PubMed

Komsa, Darya N; Staroverov, Viktor N

2016-11-08

Standard density-functional approximations often incorrectly predict that heteronuclear diatomic molecules dissociate into fractionally charged atoms. We demonstrate that these spurious charges can be eliminated by adapting the shape-correction method for Kohn-Sham potentials that was originally introduced to improve Rydberg excitation energies [ Phys. Rev. Lett. 2012 , 108 , 253005 ]. Specifically, we show that if a suitably determined fraction of electron charge is added to or removed from a frontier Kohn-Sham orbital level, the approximate Kohn-Sham potential of a stretched molecule self-corrects by developing a semblance of step structure; if this potential is used to obtain the electron density of the neutral molecule, charge delocalization is blocked and spurious fractional charges disappear beyond a certain internuclear distance.

Warm natural inflation

NASA Astrophysics Data System (ADS)

Mishra, Hiranmaya; Mohanty, Subhendra; Nautiyal, Akhilesh

2012-04-01

In warm inflation models there is the requirement of generating large dissipative couplings of the inflaton with radiation, while at the same time, not de-stabilising the flatness of the inflaton potential due to radiative corrections. One way to achieve this without fine tuning unrelated couplings is by supersymmetry. In this Letter we show that if the inflaton and other light fields are pseudo-Nambu-Goldstone bosons then the radiative corrections to the potential are suppressed and the thermal corrections are small as long as the temperature is below the symmetry breaking scale. In such models it is possible to fulfil the contrary requirements of an inflaton potential which is stable under radiative corrections and the generation of a large dissipative coupling of the inflaton field with other light fields. We construct a warm inflation model which gives the observed CMB-anisotropy amplitude and spectral index where the symmetry breaking is at the GUT scale.

Radiative corrections in the (varying power)-law modified gravity

NASA Astrophysics Data System (ADS)

Hammad, Fayçal

2015-06-01

Although the (varying power)-law modified gravity toy model has the attractive feature of unifying the early- and late-time expansions of the Universe, thanks to the peculiar dependence of the scalar field's potential on the scalar curvature, the model still suffers from the fine-tuning problem when used to explain the actually observed Hubble parameter. Indeed, a more correct estimate of the mass of the scalar field needed to comply with actual observations gives an unnaturally small value. On the other hand, for a massless scalar field the potential would have no minimum and hence the field would always remain massless. What solves these issues are the radiative corrections that modify the field's effective potential. These corrections raise the field's effective mass, rendering the model free from fine-tuning, immune against positive fifth-force tests, and better suited to tackle the dark matter sector.

Virally mediated Kcnq1 gene replacement therapy in the immature scala media restores hearing in a mouse model of human Jervell and Lange-Nielsen deafness syndrome

PubMed Central

Chang, Qing; Wang, Jianjun; Li, Qi; Kim, Yeunjung; Zhou, Binfei; Wang, Yunfeng; Li, Huawei; Lin, Xi

2015-01-01

Mutations in the potassium channel subunit KCNQ1 cause the human severe congenital deafness Jervell and Lange-Nielsen (JLN) syndrome. We applied a gene therapy approach in a mouse model of JLN syndrome (Kcnq1−/− mice) to prevent the development of deafness in the adult stage. A modified adeno-associated virus construct carrying a Kcnq1 expression cassette was injected postnatally (P0–P2) into the endolymph, which resulted in Kcnq1 expression in most cochlear marginal cells where native Kcnq1 is exclusively expressed. We also found that extensive ectopic virally mediated Kcnq1 transgene expression did not affect normal cochlear functions. Examination of cochlear morphology showed that the collapse of the Reissner’s membrane and degeneration of hair cells (HCs) and cells in the spiral ganglia were corrected in Kcnq1−/− mice. Electrophysiological tests showed normal endocochlear potential in treated ears. In addition, auditory brainstem responses showed significant hearing preservation in the injected ears, ranging from 20 dB improvement to complete correction of the deafness phenotype. Our results demonstrate the first successful gene therapy treatment for gene defects specifically affecting the function of the stria vascularis, which is a major site affected by genetic mutations in inherited hearing loss. PMID:26084842

Virally mediated Kcnq1 gene replacement therapy in the immature scala media restores hearing in a mouse model of human Jervell and Lange-Nielsen deafness syndrome.

PubMed

Chang, Qing; Wang, Jianjun; Li, Qi; Kim, Yeunjung; Zhou, Binfei; Wang, Yunfeng; Li, Huawei; Lin, Xi

2015-08-01

Mutations in the potassium channel subunit KCNQ1 cause the human severe congenital deafness Jervell and Lange-Nielsen (JLN) syndrome. We applied a gene therapy approach in a mouse model of JLN syndrome (Kcnq1(-/-) mice) to prevent the development of deafness in the adult stage. A modified adeno-associated virus construct carrying a Kcnq1 expression cassette was injected postnatally (P0-P2) into the endolymph, which resulted in Kcnq1 expression in most cochlear marginal cells where native Kcnq1 is exclusively expressed. We also found that extensive ectopic virally mediated Kcnq1 transgene expression did not affect normal cochlear functions. Examination of cochlear morphology showed that the collapse of the Reissner's membrane and degeneration of hair cells (HCs) and cells in the spiral ganglia were corrected in Kcnq1(-/-) mice. Electrophysiological tests showed normal endocochlear potential in treated ears. In addition, auditory brainstem responses showed significant hearing preservation in the injected ears, ranging from 20 dB improvement to complete correction of the deafness phenotype. Our results demonstrate the first successful gene therapy treatment for gene defects specifically affecting the function of the stria vascularis, which is a major site affected by genetic mutations in inherited hearing loss. © 2015 The Authors. Published under the terms of the CC BY 4.0 license.

Algorithms for selecting informative marker panels for population assignment.

PubMed

Rosenberg, Noah A

2005-11-01

Given a set of potential source populations, genotypes of an individual of unknown origin at a collection of markers can be used to predict the correct source population of the individual. For improved efficiency, informative markers can be chosen from a larger set of markers to maximize the accuracy of this prediction. However, selecting the loci that are individually most informative does not necessarily produce the optimal panel. Here, using genotypes from eight species--carp, cat, chicken, dog, fly, grayling, human, and maize--this univariate accumulation procedure is compared to new multivariate "greedy" and "maximin" algorithms for choosing marker panels. The procedures generally suggest similar panels, although the greedy method often recommends inclusion of loci that are not chosen by the other algorithms. In seven of the eight species, when applied to five or more markers, all methods achieve at least 94% assignment accuracy on simulated individuals, with one species--dog--producing this level of accuracy with only three markers, and the eighth species--human--requiring approximately 13-16 markers. The new algorithms produce substantial improvements over use of randomly selected markers; where differences among the methods are noticeable, the greedy algorithm leads to slightly higher probabilities of correct assignment. Although none of the approaches necessarily chooses the panel with optimal performance, the algorithms all likely select panels with performance near enough to the maximum that they all are suitable for practical use.

Mesothelioma mortality in Europe: impact of asbestos consumption and simian virus 40.

PubMed

Leithner, Katharina; Leithner, Andreas; Clar, Heimo; Weinhaeusel, Andreas; Radl, Roman; Krippl, Peter; Rehak, Peter; Windhager, Reinhard; Haas, Oskar A; Olschewski, Horst

2006-11-07

It is well established that asbestos is the most important cause of mesothelioma. The role of simian virus 40 (SV40) in mesothelioma development, on the other hand, remains controversial. This potential human oncogene has been introduced into various populations through contaminated polio vaccines. The aim of this study was to investigate whether the possible presence of SV40 in various European countries, as indicated either by molecular genetic evidence or previous exposure to SV40-contaminated vaccines, had any effect on pleural cancer rates in the respective countries. We conducted a Medline search that covered the period from January 1969 to August 2005 for reports on the detection of SV40 DNA in human tissue samples. In addition, we collected all available information about the types of polio vaccines that had been used in these European countries and their SV40 contamination status. Our ecological analysis confirms that pleural cancer mortality in males, but not in females, correlates with the extent of asbestos exposure 25 - 30 years earlier. In contrast, neither the presence of SV40 DNA in tumor samples nor a previous vaccination exposure had any detectable influence on the cancer mortality rate in neither in males (asbestos-corrected rates) nor in females. Using the currently existing data on SV40 prevalence, no association between SV40 prevalence and asbestos-corrected male pleural cancer can be demonstrated.

An analysis of pharmaceutical experience with decades of rat carcinogenicity testing: support for a proposal to modify current regulatory guidelines.

PubMed

Sistare, Frank D; Morton, Daniel; Alden, Carl; Christensen, Joel; Keller, Douglas; Jonghe, Sandra De; Storer, Richard D; Reddy, M Vijayaraj; Kraynak, Andrew; Trela, Bruce; Bienvenu, Jean-Guy; Bjurström, Sivert; Bosmans, Vanessa; Brewster, David; Colman, Karyn; Dominick, Mark; Evans, John; Hailey, James R; Kinter, Lewis; Liu, Matt; Mahrt, Charles; Marien, Dirk; Myer, James; Perry, Richard; Potenta, Daniel; Roth, Arthur; Sherratt, Philip; Singer, Thomas; Slim, Rabih; Soper, Keith; Fransson-Steen, Ronny; Stoltz, James; Turner, Oliver; Turnquist, Susan; van Heerden, Marjolein; Woicke, Jochen; DeGeorge, Joseph J

2011-06-01

Data collected from 182 marketed and nonmarketed pharmaceuticals demonstrate that there is little value gained in conducting a rat two-year carcinogenicity study for compounds that lack: (1) histopathologic risk factors for rat neoplasia in chronic toxicology studies, (2) evidence of hormonal perturbation, and (3) positive genetic toxicology results. Using a single positive result among these three criteria as a test for outcome in the two-year study, fifty-two of sixty-six rat tumorigens were correctly identified, yielding 79% test sensitivity. When all three criteria were negative, sixty-two of seventy-six pharmaceuticals (82%) were correctly predicted to be rat noncarcinogens. The fourteen rat false negatives had two-year study findings of questionable human relevance. Applying these criteria to eighty-six additional chemicals identified by the International Agency for Research on Cancer as likely human carcinogens and to drugs withdrawn from the market for carcinogenicity concerns confirmed their sensitivity for predicting rat carcinogenicity outcome. These analyses support a proposal to refine regulatory criteria for conducting a two-year rat study to be based on assessment of histopathologic findings from a rat six-month study, evidence of hormonal perturbation, genetic toxicology results, and the findings of a six-month transgenic mouse carcinogenicity study. This proposed decision paradigm has the potential to eliminate over 40% of rat two-year testing on new pharmaceuticals without compromise to patient safety.

CRISPR/Cas9 system and its applications in human hematopoietic cells.

PubMed

Hu, Xiaotang

2016-11-01

Since 2012, the CRISPR-Cas9 system has been quickly and successfully tested in a broad range of organisms and cells including hematopoietic cells. The application of CRISPR-Cas9 in human hematopoietic cells mainly involves the genes responsible for HIV infection, β-thalassemia and sickle cell disease (SCD). The successful disruption of CCR5 and CXCR4 genes in T cells by CRISPR-Cas9 promotes the prospect of the technology in the functional cure of HIV. More recently, eliminating CCR5 and CXCR4 in induced pluripotent stem cells (iPSCs) derived from patients and targeting the HIV genome have been successfully carried out in several laboratories. The outcome from these approaches bring us closer to the goal of eradicating HIV infection. For hemoglobinopathies the ability to produce iPSC-derived from patients with the correction of hemoglobin (HBB) mutations by CRISPR-Cas9 has been tested in a number of laboratories. These corrected iPSCs also show the potential to differentiate into mature erythrocytes expressing high-level and normal HBB. In light of the initial success of CRESPR-Cas9 in target mutated gene(s) in the iPSCs, a combination of genomic editing and autogenetic stem cell transplantation would be the best strategy for root treatment of the diseases, which could replace traditional allogeneic stem cell transplantation. Copyright © 2016 Elsevier Inc. All rights reserved.

Concise Review: The Potential Use of Intestinal Stem Cells to Treat Patients with Intestinal Failure.

PubMed

Hong, Sung Noh; Dunn, James C Y; Stelzner, Matthias; Martín, Martín G

2017-02-01

Intestinal failure is a rare life-threatening condition that results in the inability to maintain normal growth and hydration status by enteral nutrition alone. Although parenteral nutrition and whole organ allogeneic transplantation have improved the survival of these patients, current therapies are associated with a high risk for morbidity and mortality. Development of methods to propagate adult human intestinal stem cells (ISCs) and pluripotent stem cells raises the possibility of using stem cell-based therapy for patients with monogenic and polygenic forms of intestinal failure. Organoids have demonstrated the capacity to proliferate indefinitely and differentiate into the various cellular lineages of the gut. Genome-editing techniques, including the overexpression of the corrected form of the defective gene, or the use of CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 to selectively correct the monogenic disease-causing variant within the stem cell, make autologous ISC transplantation a feasible approach. However, numerous techniques still need to be further optimized, including more robust ex vivo ISC expansion, native ISC ablation, and engraftment protocols. Large-animal models can to be used to develop such techniques and protocols and to establish the safety of autologous ISC transplantation because outcomes in such models can be extrapolated more readily to humans. Stem Cells Translational Medicine 2017;6:666-676. © 2016 The Authors Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

21 CFR 820.100 - Corrective and preventive action.

Code of Federal Regulations, 2013 CFR

2013-04-01

..., work operations, concessions, quality audit reports, quality records, service records, complaints, returned product, and other sources of quality data to identify existing and potential causes of... (CONTINUED) MEDICAL DEVICES QUALITY SYSTEM REGULATION Corrective and Preventive Action § 820.100 Corrective...

21 CFR 820.100 - Corrective and preventive action.

Code of Federal Regulations, 2011 CFR

2011-04-01

..., work operations, concessions, quality audit reports, quality records, service records, complaints, returned product, and other sources of quality data to identify existing and potential causes of... (CONTINUED) MEDICAL DEVICES QUALITY SYSTEM REGULATION Corrective and Preventive Action § 820.100 Corrective...

21 CFR 820.100 - Corrective and preventive action.

Code of Federal Regulations, 2010 CFR

2010-04-01

..., work operations, concessions, quality audit reports, quality records, service records, complaints, returned product, and other sources of quality data to identify existing and potential causes of... (CONTINUED) MEDICAL DEVICES QUALITY SYSTEM REGULATION Corrective and Preventive Action § 820.100 Corrective...

21 CFR 820.100 - Corrective and preventive action.

Code of Federal Regulations, 2012 CFR

2012-04-01

..., work operations, concessions, quality audit reports, quality records, service records, complaints, returned product, and other sources of quality data to identify existing and potential causes of... (CONTINUED) MEDICAL DEVICES QUALITY SYSTEM REGULATION Corrective and Preventive Action § 820.100 Corrective...

21 CFR 820.100 - Corrective and preventive action.

Code of Federal Regulations, 2014 CFR

2014-04-01

..., work operations, concessions, quality audit reports, quality records, service records, complaints, returned product, and other sources of quality data to identify existing and potential causes of... (CONTINUED) MEDICAL DEVICES QUALITY SYSTEM REGULATION Corrective and Preventive Action § 820.100 Corrective...

Breakdown of the single-exchange approximation in third-order symmetry-adapted perturbation theory.

PubMed

Lao, Ka Un; Herbert, John M

2012-03-22

We report third-order symmetry-adapted perturbation theory (SAPT) calculations for several dimers whose intermolecular interactions are dominated by induction. We demonstrate that the single-exchange approximation (SEA) employed to derive the third-order exchange-induction correction (E(exch-ind)((30))) fails to quench the attractive nature of the third-order induction (E(ind)((30))), leading to one-dimensional potential curves that become attractive rather than repulsive at short intermolecular separations. A scaling equation for (E(exch-ind)((30))), based on an exact formula for the first-order exchange correction, is introduced to approximate exchange effects beyond the SEA, and qualitatively correct potential energy curves that include third-order induction are thereby obtained. For induction-dominated systems, our results indicate that a "hybrid" SAPT approach, in which a dimer Hartree-Fock calculation is performed in order to obtain a correction for higher-order induction, is necessary not only to obtain quantitative binding energies but also to obtain qualitatively correct potential energy surfaces. These results underscore the need to develop higher-order exchange-induction formulas that go beyond the SEA. © 2012 American Chemical Society

CRISPR/Cas9 and cancer targets: future possibilities and present challenges.

PubMed

White, Martyn K; Khalili, Kamel

2016-03-15

All cancers have multiple mutations that can largely be grouped into certain classes depending on the function of the gene in which they lie and these include oncogenic changes that enhance cellular proliferation, loss of function of tumor suppressors that regulate cell growth potential and induction of metabolic enzymes that confer resistance to chemotherapeutic agents. Thus the ability to correct such mutations is an important goal in cancer treatment. Recent research has led to the developments of reagents which specifically target nucleotide sequences within the cellular genome and these have a huge potential for expanding our anticancer armamentarium. One such a reagent is the clustered regulatory interspaced short palindromic repeat (CRISPR)-associated 9 (Cas9) system, a powerful, highly specific and adaptable tool that provides unparalleled control for editing the cellular genome. In this short review, we discuss the potential of CRISPR/Cas9 against human cancers and the current difficulties in translating this for novel therapeutic approaches.

Double ErrP Detection for Automatic Error Correction in an ERP-Based BCI Speller.

PubMed

Cruz, Aniana; Pires, Gabriel; Nunes, Urbano J

2018-01-01

Brain-computer interface (BCI) is a useful device for people with severe motor disabilities. However, due to its low speed and low reliability, BCI still has a very limited application in daily real-world tasks. This paper proposes a P300-based BCI speller combined with a double error-related potential (ErrP) detection to automatically correct erroneous decisions. This novel approach introduces a second error detection to infer whether wrong automatic correction also elicits a second ErrP. Thus, two single-trial responses, instead of one, contribute to the final selection, improving the reliability of error detection. Moreover, to increase error detection, the evoked potential detected as target by the P300 classifier is combined with the evoked error potential at a feature-level. Discriminable error and positive potentials (response to correct feedback) were clearly identified. The proposed approach was tested on nine healthy participants and one tetraplegic participant. The online average accuracy for the first and second ErrPs were 88.4% and 84.8%, respectively. With automatic correction, we achieved an improvement around 5% achieving 89.9% in spelling accuracy for an effective 2.92 symbols/min. The proposed approach revealed that double ErrP detection can improve the reliability and speed of BCI systems.

Certify for success: A methodology for human-centered certification of advanced aviation systems

NASA Technical Reports Server (NTRS)

Small, Ronald L.; Rouse, William B.

1994-01-01

This position paper uses the methodology in Design for Success as a basis for a human factors certification program. The Design for Success (DFS) methodology espouses a multi-step process to designing and developing systems in a human-centered fashion. These steps are as follows: (1) naturalizing - understand stakeholders and their concerns; (2) marketing - understand market-oriented alternatives to meeting stakeholder concerns; (3) engineering - detailed design and development of the system considering tradeoffs between technology, cost, schedule, certification requirements, etc.; (4) system evaluation - determining if the system meets its goal(s); and (5) sales and service - delivering and maintaining the system. Because the main topic of this paper is certification, we will focus our attention on step 4, System Evaluation, since it is the natural precursor to certification. Evaluation involves testing the system and its parts for their correct behaviors. Certification focuses not only on ensuring that the system exhibits the correct behaviors, but ONLY the correct behaviors.

Genetic correction of tauopathy phenotypes in neurons derived from human induced pluripotent stem cells.

PubMed

Fong, Helen; Wang, Chengzhong; Knoferle, Johanna; Walker, David; Balestra, Maureen E; Tong, Leslie M; Leung, Laura; Ring, Karen L; Seeley, William W; Karydas, Anna; Kshirsagar, Mihir A; Boxer, Adam L; Kosik, Kenneth S; Miller, Bruce L; Huang, Yadong

2013-01-01

Tauopathies represent a group of neurodegenerative disorders characterized by the accumulation of pathological TAU protein in brains. We report a human neuronal model of tauopathy derived from induced pluripotent stem cells (iPSCs) carrying a TAU-A152T mutation. Using zinc-finger nuclease-mediated gene editing, we generated two isogenic iPSC lines: one with the mutation corrected, and another with the homozygous mutation engineered. The A152T mutation increased TAU fragmentation and phosphorylation, leading to neurodegeneration and especially axonal degeneration. These cellular phenotypes were consistent with those observed in a patient with TAU-A152T. Upon mutation correction, normal neuronal and axonal morphologies were restored, accompanied by decreases in TAU fragmentation and phosphorylation, whereas the severity of tauopathy was intensified in neurons with the homozygous mutation. These isogenic TAU-iPSC lines represent a critical advancement toward the accurate modeling and mechanistic study of tauopathies with human neurons and will be invaluable for drug-screening efforts and future cell-based therapies.

77 FR 33737 - Findings of Research Misconduct; Correction

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-07

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Office of the Secretary Findings of Research Misconduct... of Research Misconduct.'' DATES: Effective Date: June 7, 2012. Applicability Date: The correction notice is applicable for the Findings of Research Misconduct notice published on May 31, 2012. FOR...

Correction to: Transplantation of Human Chorion-Derived Cholinergic Progenitor Cells: a Novel Treatment for Neurological Disorders.

PubMed

Mohammadi, Alireza; Maleki-Jamshid, Ali; Sanooghi, Davood; Milan, Peiman Brouki; Rahmani, Arash; Sefat, Farshid; Shahpasand, Koorosh; Soleimani, Mansoureh; Bakhtiari, Mehrdad; Belali, Rafie; Faghihi, Faezeh; Joghataei, Mohammad Taghi; Perry, George; Mozafari, Masoud

2018-04-26

The original version of this article unfortunately contained mistake in the affiliation. Affiliation 1 should be read as "Neuroscience Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran". The original article has been corrected.

Closure Report for Corrective Action Unit 117: Area 26 Pluto Disassembly Facility, Nevada Test Site, Nevada, Revision 0

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

Mark Burmeister

This Closure Report (CR) presents information supporting the closure of Corrective Action Unit (CAU) 117: Area 26 Pluto Disassembly Facility, Nevada Test Site, Nevada. This CR complies with the requirements of the Federal Facility Agreement and Consent Order that was agreed to by the State of Nevada; U.S. Department of Energy (DOE), Environmental Management; U.S. Department of Defense; and DOE, Legacy Management. Corrective Action Unit 117 comprises Corrective Action Site (CAS) 26-41-01, Pluto Disassembly Facility, located in Area 26 of the Nevada Test Site. The purpose of this CR is to provide documentation supporting the completed corrective actions and providemore » data confirming that the closure objectives for CAU 117 were met. To achieve this, the following actions were performed: • Review the current site conditions, including the concentration and extent of contamination. • Implement any corrective actions necessary to protect human health and the environment. • Properly dispose of corrective action and investigation wastes. • Document Notice of Completion and closure of CAU 117 issued by the Nevada Division of Environmental Protection. From May 2008 through February 2009, closure activities were performed as set forth in the Streamlined Approach for Environmental Restoration Plan for Corrective Action Unit 117, Area 26 Pluto Disassembly Facility, Nevada Test Site, Nevada. The purpose of the activities as defined during the data quality objectives process were: • Determine whether contaminants of concern (COCs) are present. • If COCs are present, determine their nature and extent, implement appropriate corrective actions, and properly dispose of wastes. Analytes detected during the closure activities were evaluated against final action levels to determine COCs for CAU 117. Assessment of the data generated from closure activities indicated that the final action levels were exceeded for polychlorinated biphenyls (PCBs) reported as total Aroclor and radium-226. A corrective action was implemented to remove approximately 50 cubic yards of PCB-contaminated soil, approximately 1 cubic foot of radium-226 contaminated soil (and scabbled asphalt), and a high-efficiency particulate air filter that was determined to meet the criteria of a potential source material (PSM). Electrical and lighting components (i.e., PCB-containing ballasts and capacitors) and other materials (e.g., mercury-containing thermostats and switches, lead plugs and bricks) assumed to be PSM were also removed from Building 2201, as practical, without the need for sampling. Because the COC contamination and PSMs have been removed, clean closure of CAS 26-41-01 is recommended, and no use restrictions are required to be placed on this CAU. No further action is necessary because no other contaminants of potential concern were found above preliminary action levels. The physical end state for Building 2201 is expected to be eventual demolition to slab. The DOE, National Nuclear Security Administration Nevada Site Office provides the following recommendations: • Clean closure is the recommended corrective action for CAS 26-41-01 in CAU 117. • A Notice of Completion to the DOE, National Nuclear Security Administration Nevada Site Office is requested from the Nevada Division of Environmental Protection for closure of CAU 117. • Corrective Action Unit 117 should be moved from Appendix III to Appendix IV of the Federal Facility Agreement and Consent Order.« less

Exposed and embedded corrections in aphasia therapy: issues of voice and identity.

PubMed

Simmons-Mackie, Nina; Damico, Jack S

2008-01-01

Because communication after the onset of aphasia can be fraught with errors, therapist corrections are pervasive in therapy for aphasia. Although corrections are designed to improve the accuracy of communication, some corrections can have social and emotional consequences during interactions. That is, exposure of errors can potentially silence the 'voice' of a speaker by orienting to an utterance as unacceptable. Although corrections can marginalize speakers with aphasia, the practice has not been widely investigated. A qualitative study of corrections during aphasia therapy was undertaken to describe corrections in therapy, identify patterns of occurrence, and develop hypotheses regarding the potential effects of corrections. Videotapes of six individual and five group aphasia therapy sessions were analysed. Sequences consistent with a definition of a therapist 'correction' were identified. Corrections were defined as instances when the therapist offered a 'fix' for a perceived error in the client's talk even though the intent was apparent. Two categories of correction were identified and were consistent with Jefferson's (1987) descriptions of exposed and embedded corrections. Exposed corrections involved explicit correcting by the therapist, while embedded corrections occurred implicitly within the ongoing talk. Patterns of occurrence appeared consistent with philosophical orientations of therapy sessions. Exposed corrections were more prevalent in sessions focusing on repairing deficits, while embedded corrections were prevalent in sessions focusing on natural communication events (e.g. conversation). In addition, exposed corrections were sometimes used when client offerings were plausible or appropriate, but were inconsistent with therapist expectations. The observation that some instances of exposed corrections effectively silenced the voice or self-expression of the person with aphasia has significant implications for outcomes from aphasia therapy. By focusing on accurate productions versus communicative intents, therapy runs the risk of reducing self-esteem and communicative confidence, as well as reinforcing a sense of 'helplessness' and disempowerment among people with aphasia. The results suggest that clinicians should carefully calibrate the use of exposed and embedded corrections to balance linguistic and psychosocial goals.

Machine Learned Replacement of N-Labels for Basecalled Sequences in DNA Barcoding.

PubMed

Ma, Eddie Y T; Ratnasingham, Sujeevan; Kremer, Stefan C

2018-01-01

This study presents a machine learning method that increases the number of identified bases in Sanger Sequencing. The system post-processes a KB basecalled chromatogram. It selects a recoverable subset of N-labels in the KB-called chromatogram to replace with basecalls (A,C,G,T). An N-label correction is defined given an additional read of the same sequence, and a human finished sequence. Corrections are added to the dataset when an alignment determines the additional read and human agree on the identity of the N-label. KB must also rate the replacement with quality value of in the additional read. Corrections are only available during system training. Developing the system, nearly 850,000 N-labels are obtained from Barcode of Life Datasystems, the premier database of genetic markers called DNA Barcodes. Increasing the number of correct bases improves reference sequence reliability, increases sequence identification accuracy, and assures analysis correctness. Keeping with barcoding standards, our system maintains an error rate of percent. Our system only applies corrections when it estimates low rate of error. Tested on this data, our automation selects and recovers: 79 percent of N-labels from COI (animal barcode); 80 percent from matK and rbcL (plant barcodes); and 58 percent from non-protein-coding sequences (across eukaryotes).

Generation of Healthy Mice from Gene-Corrected Disease-Specific Induced Pluripotent Stem Cells

PubMed Central

Rittelmeyer, Ina; Sharma, Amar Deep; Sgodda, Malte; Zaehres, Holm; Bleidißel, Martina; Greber, Boris; Gentile, Luca; Han, Dong Wook; Rudolph, Cornelia; Steinemann, Doris; Schambach, Axel; Ott, Michael; Schöler, Hans R.; Cantz, Tobias

2011-01-01

Using the murine model of tyrosinemia type 1 (fumarylacetoacetate hydrolase [FAH] deficiency; FAH −/− mice) as a paradigm for orphan disorders, such as hereditary metabolic liver diseases, we evaluated fibroblast-derived FAH −/−-induced pluripotent stem cells (iPS cells) as targets for gene correction in combination with the tetraploid embryo complementation method. First, after characterizing the FAH −/− iPS cell lines, we aggregated FAH −/−-iPS cells with tetraploid embryos and obtained entirely FAH −/−-iPS cell–derived mice that were viable and exhibited the phenotype of the founding FAH −/− mice. Then, we transduced FAH cDNA into the FAH −/−-iPS cells using a third-generation lentiviral vector to generate gene-corrected iPS cells. We could not detect any chromosomal alterations in these cells by high-resolution array CGH analysis, and after their aggregation with tetraploid embryos, we obtained fully iPS cell–derived healthy mice with an astonishing high efficiency for full-term development of up to 63.3%. The gene correction was validated functionally by the long-term survival and expansion of FAH-positive cells of these mice after withdrawal of the rescuing drug NTBC (2-(2-nitro-4-fluoromethylbenzoyl)-1,3-cyclohexanedione). Furthermore, our results demonstrate that both a liver-specific promoter (transthyretin, TTR)-driven FAH transgene and a strong viral promoter (from spleen focus-forming virus, SFFV)-driven FAH transgene rescued the FAH-deficiency phenotypes in the mice derived from the respective gene-corrected iPS cells. In conclusion, our data demonstrate that a lentiviral gene repair strategy does not abrogate the full pluripotent potential of fibroblast-derived iPS cells, and genetic manipulation of iPS cells in combination with tetraploid embryo aggregation provides a practical and rapid approach to evaluate the efficacy of gene correction of human diseases in mouse models. PMID:21765802

Activation of the Cystic Fibrosis Transmembrane Conductance Regulator by the Flavonoid Quercetin

PubMed Central

Pyle, Louise C.; Fulton, Jennifer C.; Sloane, Peter A.; Backer, Kyle; Mazur, Marina; Prasain, Jeevan; Barnes, Stephen; Clancy, J. P.; Rowe, Steven M.

2010-01-01

Therapies to correct the ΔF508 cystic fibrosis transmembrane conductance regulator (CFTR) folding defect require sensitive methods to detect channel activity in vivo. The β2 adrenergic receptor agonists, which provide the CFTR stimuli commonly used in nasal potential difference assays, may not overcome the channel gating defects seen in ΔF508 CFTR after plasma membrane localization. In this study, we identify an agent, quercetin, that enhances the detection of surface ΔF508 CFTR, and is suitable for nasal perfusion. A screen of flavonoids in CFBE41o− cells stably transduced with ΔF508 CFTR, corrected to the cell surface with low temperature growth, revealed that quercetin stimulated an increase in the short-circuit current. This increase was dose-dependent in both Fisher rat thyroid and CFBE41o− cells. High concentrations inhibited Cl− conductance. In CFBE41o− airway cells, quercetin (20 μg/ml) activated ΔF508 CFTR, whereas the β2 adrenergic receptor agonist isoproterenol did not. Quercetin had limited effects on cAMP levels, but did not produce detectable phosphorylation of the isolated CFTR R-domain, suggesting an activation independent of channel phosphorylation. When perfused in the nares of Cftr+ mice, quercetin (20 μg/ml) produced a hyperpolarization of the potential difference that was absent in Cftr−/− mice. Finally, quercetin-induced, dose-dependent hyperpolarization of the nasal potential difference was also seen in normal human subjects. Quercetin activates CFTR-mediated anion transport in respiratory epithelia in vitro and in vivo, and may be useful in studies intended to detect the rescue of ΔF508 CFTR by nasal potential difference. PMID:20042712

QSAR models of human data can enrich or replace LLNA testing for human skin sensitization

PubMed Central

Alves, Vinicius M.; Capuzzi, Stephen J.; Muratov, Eugene; Braga, Rodolpho C.; Thornton, Thomas; Fourches, Denis; Strickland, Judy; Kleinstreuer, Nicole; Andrade, Carolina H.; Tropsha, Alexander

2016-01-01

Skin sensitization is a major environmental and occupational health hazard. Although many chemicals have been evaluated in humans, there have been no efforts to model these data to date. We have compiled, curated, analyzed, and compared the available human and LLNA data. Using these data, we have developed reliable computational models and applied them for virtual screening of chemical libraries to identify putative skin sensitizers. The overall concordance between murine LLNA and human skin sensitization responses for a set of 135 unique chemicals was low (R = 28-43%), although several chemical classes had high concordance. We have succeeded to develop predictive QSAR models of all available human data with the external correct classification rate of 71%. A consensus model integrating concordant QSAR predictions and LLNA results afforded a higher CCR of 82% but at the expense of the reduced external dataset coverage (52%). We used the developed QSAR models for virtual screening of CosIng database and identified 1061 putative skin sensitizers; for seventeen of these compounds, we found published evidence of their skin sensitization effects. Models reported herein provide more accurate alternative to LLNA testing for human skin sensitization assessment across diverse chemical data. In addition, they can also be used to guide the structural optimization of toxic compounds to reduce their skin sensitization potential. PMID:28630595

A feasibility study of using event-related potential as a biometrics.

PubMed

Yih-Choung Yu; Sicheng Wang; Gabel, Lisa A

2016-08-01

The use of an individual's neural response to stimuli (the event-related potential or ERP) has potential as a biometric because it is highly resistant to fraud relative to other conventional authentication systems. P300 is an ERP in human electroencephalography (EEG) that occurs in response to an oddball stimulus when an individual is actively engaged in a target detection task. Because P300 is consistently detectable from almost every subject, it is considered a potential signal for biometric applications. This paper presents a feasibility study of using topological plots of P300 as a biometric in subject authentication. The variation in latency and location of P300 response of 24 participants performing the P300Speller task were studied. Data sets from four participants were used for algorithm training; data from the other 20 participants were used as imposters for algorithm validation. The result showed that the algorithm was able to correctly identify three out of these four participants. Validation test also proved that the algorithm was able to reject 95% of the imposters for those three authenticated participants.

Estimation of human emotions using thermal facial information

NASA Astrophysics Data System (ADS)

Nguyen, Hung; Kotani, Kazunori; Chen, Fan; Le, Bac

2014-01-01

In recent years, research on human emotion estimation using thermal infrared (IR) imagery has appealed to many researchers due to its invariance to visible illumination changes. Although infrared imagery is superior to visible imagery in its invariance to illumination changes and appearance differences, it has difficulties in handling transparent glasses in the thermal infrared spectrum. As a result, when using infrared imagery for the analysis of human facial information, the regions of eyeglasses are dark and eyes' thermal information is not given. We propose a temperature space method to correct eyeglasses' effect using the thermal facial information in the neighboring facial regions, and then use Principal Component Analysis (PCA), Eigen-space Method based on class-features (EMC), and PCA-EMC method to classify human emotions from the corrected thermal images. We collected the Kotani Thermal Facial Emotion (KTFE) database and performed the experiments, which show the improved accuracy rate in estimating human emotions.

Potential Protein Toxicity of Synthetic Pigments: Binding of Poncean S to Human Serum Albumin☆

PubMed Central

Gao, Hong-Wen; Xu, Qing; Chen, Ling; Wang, Shi-Long; Wang, Yuan; Wu, Ling-Ling; Yuan, Yuan

2008-01-01

Using various methods, e.g., spectrophotometry, circular dichroism, and isothermal titration calorimetry, the interaction of poncean S (PS) with human serum albumin (HSA) was characterized at pH 1.81, 3.56, and 7.40 using the spectral correction technique, and Langmuir and Temkin isothermal models. The consistency among results concerning, e.g., binding number, binding energy, and type of binding, showed that ion pair electrostatic attraction fixed the position of PS in HSA and subsequently induced a combination of multiple noncovalent bonds such as H-bonds, hydrophobic interactions, and van der Waals forces. Ion pair attraction and H-bonds produced a stable PS-HSA complex and led to a marked change in the secondary structure of HSA in acidic media. The PS-HSA binding pattern and the process of change in HSA conformation were also investigated. The potentially toxic effect of PS on the transport function of HSA in a normal physiological environment was analyzed. This work provides a useful experimental strategy for studying the interaction of organic substances with biomacromolecules, helping us to understand the activity or mechanism of toxicity of an organic compound. PMID:17905844

Multiple sensor integration for seizure onset detection in human patients comparing conventional disc versus novel tripolar concentric ring electrodes.

PubMed

Makeyev, Oleksandr; Ding, Quan; Martínez-Juárez, Iris E; Gaitanis, John; Kay, Steven M; Besio, Walter G

2013-01-01

As epilepsy affects approximately one percent of the world population, electrical stimulation of the brain has recently shown potential for additive seizure control therapy. Closed-loop systems that apply electrical stimulation when seizure onset is automatically detected require high accuracy of automatic seizure detection based on electrographic brain activity. To improve this accuracy we propose to use noninvasive tripolar concentric ring electrodes that have been shown to have significantly better signal-to-noise ratio, spatial selectivity, and mutual information compared to conventional disc electrodes. The proposed detection methodology is based on integration of multiple sensors using exponentially embedded family (EEF). In this preliminary study it is validated on over 26.3 hours of data collected using both tripolar concentric ring and conventional disc electrodes concurrently each from 7 human patients with epilepsy including five seizures. For a cross-validation based group model EEF correctly detected 100% and 80% of seizures respectively with <0.76 and <1.56 false positive detections per hour respectively for the two electrode modalities. These results clearly suggest the potential of seizure onset detection based on data from tripolar concentric ring electrodes.

Creating a monomeric endonuclease TALE-I-SceI with high specificity and low genotoxicity in human cells.

PubMed

Lin, Jianfei; Chen, He; Luo, Ling; Lai, Yongrong; Xie, Wei; Kee, Kehkooi

2015-01-01

To correct a DNA mutation in the human genome for gene therapy, homology-directed repair (HDR) needs to be specific and have the lowest off-target effects to protect the human genome from deleterious mutations. Zinc finger nucleases, transcription activator-like effector nuclease (TALEN) and CRISPR-CAS9 systems have been engineered and used extensively to recognize and modify specific DNA sequences. Although TALEN and CRISPR/CAS9 could induce high levels of HDR in human cells, their genotoxicity was significantly higher. Here, we report the creation of a monomeric endonuclease that can recognize at least 33 bp by fusing the DNA-recognizing domain of TALEN (TALE) to a re-engineered homing endonuclease I-SceI. After sequentially re-engineering I-SceI to recognize 18 bp of the human β-globin sequence, the re-engineered I-SceI induced HDR in human cells. When the re-engineered I-SceI was fused to TALE (TALE-ISVB2), the chimeric endonuclease induced the same HDR rate at the human β-globin gene locus as that induced by TALEN, but significantly reduced genotoxicity. We further demonstrated that TALE-ISVB2 specifically targeted at the β-globin sequence in human hematopoietic stem cells. Therefore, this monomeric endonuclease has the potential to be used in therapeutic gene targeting in human cells. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

Probabilistic analysis showing that a combination of bacteroides and methanobrevibacter source tracking markers is effective for identifying waters contaminated by human fecal pollution

USGS Publications Warehouse

Johnston, Christopher; Byappanahalli, Muruleedhara N.; Gibson, Jacqueline MacDonald; Ufnar, Jennifer A.; Whitman, Richard L.; Stewart, Jill R.

2013-01-01

Microbial source tracking assays to identify sources of waterborne contamination typically target genetic markers of host-specific microorganisms. However, no bacterial marker has been shown to be 100% host-specific, and cross-reactivity has been noted in studies evaluating known source samples. Using 485 challenge samples from 20 different human and animal fecal sources, this study evaluated microbial source tracking markers including the Bacteroides HF183 16S rRNA, M. smithii nifH, and Enterococcus esp gene targets that have been proposed as potential indicators of human fecal contamination. Bayes' Theorem was used to calculate the conditional probability that these markers or a combination of markers can correctly identify human sources of fecal pollution. All three human-associated markers were detected in 100% of the sewage samples analyzed. Bacteroides HF183 was the most effective marker for determining whether contamination was specifically from a human source, and greater than 98% certainty that contamination was from a human source was shown when both Bacteroides HF183 and M. smithii nifH markers were present. A high degree of certainty was attained even in cases where the prior probability of human fecal contamination was as low as 8.5%. The combination of Bacteroides HF183 and M. smithii nifH source tracking markers can help identify surface waters impacted by human fecal contamination, information useful for prioritizing restoration activities or assessing health risks from exposure to contaminated waters.

Sample size, library composition, and genotypic diversity among natural populations of Escherichia coli from different animals influence accuracy of determining sources of fecal pollution.

PubMed

Johnson, LeeAnn K; Brown, Mary B; Carruthers, Ethan A; Ferguson, John A; Dombek, Priscilla E; Sadowsky, Michael J

2004-08-01

A horizontal, fluorophore-enhanced, repetitive extragenic palindromic-PCR (rep-PCR) DNA fingerprinting technique (HFERP) was developed and evaluated as a means to differentiate human from animal sources of Escherichia coli. Box A1R primers and PCR were used to generate 2,466 rep-PCR and 1,531 HFERP DNA fingerprints from E. coli strains isolated from fecal material from known human and 12 animal sources: dogs, cats, horses, deer, geese, ducks, chickens, turkeys, cows, pigs, goats, and sheep. HFERP DNA fingerprinting reduced within-gel grouping of DNA fingerprints and improved alignment of DNA fingerprints between gels, relative to that achieved using rep-PCR DNA fingerprinting. Jackknife analysis of the complete rep-PCR DNA fingerprint library, done using Pearson's product-moment correlation coefficient, indicated that animal and human isolates were assigned to the correct source groups with an 82.2% average rate of correct classification. However, when only unique isolates were examined, isolates from a single animal having a unique DNA fingerprint, Jackknife analysis showed that isolates were assigned to the correct source groups with a 60.5% average rate of correct classification. The percentages of correctly classified isolates were about 15 and 17% greater for rep-PCR and HFERP, respectively, when analyses were done using the curve-based Pearson's product-moment correlation coefficient, rather than the band-based Jaccard algorithm. Rarefaction analysis indicated that, despite the relatively large size of the known-source database, genetic diversity in E. coli was very great and is most likely accounting for our inability to correctly classify many environmental E. coli isolates. Our data indicate that removal of duplicate genotypes within DNA fingerprint libraries, increased database size, proper methods of statistical analysis, and correct alignment of band data within and between gels improve the accuracy of microbial source tracking methods.

Corrective Action Investigation Plan for Corrective Action Unit 165: Areas 25 and 26 Dry Well and Washdown Areas, Nevada Test Site, Nevada (including Record of Technical Change Nos. 1, 2, and 3) (January 2002, Rev. 0)

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

U.S. Department of Energy, National Nuclear Security Administration Nevada Operations Office

This Corrective Action Investigation Plan contains the U.S. Department of Energy, National Nuclear Security Administration Nevada Operations Office's approach to collect the data necessary to evaluate corrective action alternatives appropriate for the closure of Corrective Action Unit (CAU) 165 under the Federal Facility Agreement and Consent Order. Corrective Action Unit 165 consists of eight Corrective Action Sites (CASs): CAS 25-20-01, Lab Drain Dry Well; CAS 25-51-02, Dry Well; CAS 25-59-01, Septic System; CAS 26-59-01, Septic System; CAS 25-07-06, Train Decontamination Area; CAS 25-07-07, Vehicle Washdown; CAS 26-07-01, Vehicle Washdown Station; and CAS 25-47-01, Reservoir and French Drain. All eight CASsmore » are located in the Nevada Test Site, Nevada. Six of these CASs are located in Area 25 facilities and two CASs are located in Area 26 facilities. The eight CASs at CAU 165 consist of dry wells, septic systems, decontamination pads, and a reservoir. The six CASs in Area 25 are associated with the Nuclear Rocket Development Station that operated from 1958 to 1973. The two CASs in Area 26 are associated with facilities constructed for Project Pluto, a series of nuclear reactor tests conducted between 1961 to 1964 to develop a nuclear-powered ramjet engine. Based on site history, the scope of this plan will be a two-phased approach to investigate the possible presence of hazardous and/or radioactive constituents at concentrations that could potentially pose a threat to human health and the environment. The Phase I analytical program for most CASs will include volatile organic compounds, semivolatile organic compounds, Resource Conservation and Recovery Act metals, total petroleum hydrocarbons, polychlorinated biphenyls, and radionuclides. If laboratory data obtained from the Phase I investigation indicates the presence of contaminants of concern, the process will continue with a Phase II investigation to define the extent of contamination. Based on the results of Phase I sampling, the analytical program for Phase II investigation may be reduced. The results of this field investigation will support a defensible evaluation of corrective action alternatives in the corrective action decision document.« less

78 FR 61363 - Correction-Scientific Information Request on Medication Therapy Management

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-03

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Agency for Healthcare Research and Quality Correction--Scientific Information Request on Medication Therapy Management The original date of publication for this....AHRQ.gov/index.cfm/submit-scientific-information-packets/ Dated: September 27, 2013. Richard Kronick...

Intelligent OCR Processing.

ERIC Educational Resources Information Center

Sun, Wei; And Others

1992-01-01

Identifies types and distributions of errors in text produced by optical character recognition (OCR) and proposes a process using machine learning techniques to recognize and correct errors in OCR texts. Results of experiments indicating that this strategy can reduce human interaction required for error correction are reported. (25 references)…

75 FR 6670 - Findings of Misconduct in Science; Correction

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-10

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Office of the Secretary Findings of Misconduct in Science... Register entitled ``Findings of Misconduct in Science.'' DATES: Effective Date: February 10, 2010. Applicability Date: The correction notice is applicable for the Findings of Misconduct in Science notice...

3D porous calcium-alginate scaffolds cell culture system improved human osteoblast cell clusters for cell therapy.

PubMed

Chen, Ching-Yun; Ke, Cherng-Jyh; Yen, Ko-Chung; Hsieh, Hui-Chen; Sun, Jui-Sheng; Lin, Feng-Huei

2015-01-01

Age-related orthopedic disorders and bone defects have become a critical public health issue, and cell-based therapy is potentially a novel solution for issues surrounding bone tissue engineering and regenerative medicine. Long-term cultures of primary bone cells exhibit phenotypic and functional degeneration; therefore, culturing cells or tissues suitable for clinical use remain a challenge. A platform consisting of human osteoblasts (hOBs), calcium-alginate (Ca-Alginate) scaffolds, and a self-made bioreactor system was established for autologous transplantation of human osteoblast cell clusters. The Ca-Alginate scaffold facilitated the growth and differentiation of human bone cell clusters, and the functionally-closed process bioreactor system supplied the soluble nutrients and osteogenic signals required to maintain the cell viability. This system preserved the proliferative ability of cells and cell viability and up-regulated bone-related gene expression and biological apatite crystals formation. The bone-like tissue generated could be extracted by removal of calcium ions via ethylenediaminetetraacetic acid (EDTA) chelation, and exhibited a size suitable for injection. The described strategy could be used in therapeutic application and opens new avenues for surgical interventions to correct skeletal defects.

Fanconi anemia gene editing by the CRISPR/Cas9 system.

PubMed

Osborn, Mark J; Gabriel, Richard; Webber, Beau R; DeFeo, Anthony P; McElroy, Amber N; Jarjour, Jordan; Starker, Colby G; Wagner, John E; Joung, J Keith; Voytas, Daniel F; von Kalle, Christof; Schmidt, Manfred; Blazar, Bruce R; Tolar, Jakub

2015-02-01

Genome engineering with designer nucleases is a rapidly progressing field, and the ability to correct human gene mutations in situ is highly desirable. We employed fibroblasts derived from a patient with Fanconi anemia as a model to test the ability of the clustered regularly interspaced short palindromic repeats/Cas9 nuclease system to mediate gene correction. We show that the Cas9 nuclease and nickase each resulted in gene correction, but the nickase, because of its ability to preferentially mediate homology-directed repair, resulted in a higher frequency of corrected clonal isolates. To assess the off-target effects, we used both a predictive software platform to identify intragenic sequences of homology as well as a genome-wide screen utilizing linear amplification-mediated PCR. We observed no off-target activity and show RNA-guided endonuclease candidate sites that do not possess low sequence complexity function in a highly specific manner. Collectively, we provide proof of principle for precision genome editing in Fanconi anemia, a DNA repair-deficient human disorder.

Super-resolution pupil filtering for visual performance enhancement using adaptive optics

NASA Astrophysics Data System (ADS)

Zhao, Lina; Dai, Yun; Zhao, Junlei; Zhou, Xiaojun

2018-05-01

Ocular aberration correction can significantly improve visual function of the human eye. However, even under ideal aberration correction conditions, pupil diffraction restricts the resolution of retinal images. Pupil filtering is a simple super-resolution (SR) method that can overcome this diffraction barrier. In this study, a 145-element piezoelectric deformable mirror was used as a pupil phase filter because of its programmability and high fitting accuracy. Continuous phase-only filters were designed based on Zernike polynomial series and fitted through closed-loop adaptive optics. SR results were validated using double-pass point spread function images. Contrast sensitivity was further assessed to verify the SR effect on visual function. An F-test was conducted for nested models to statistically compare different CSFs. These results indicated CSFs for the proposed SR filter were significantly higher than the diffraction correction (p < 0.05). As such, the proposed filter design could provide useful guidance for supernormal vision optical correction of the human eye.

Simulation of Ametropic Human Eyes

NASA Astrophysics Data System (ADS)

Tan, Bo; Chen, Ying-Ling; Lewis, James W. L.

2004-11-01

The computational simulation of the performance of human eyes is complex because the optical parameters of the eye depend on many factors, including age, gender, race, refractive status (accommodation and near- or far-sightedness). This task is made more difficult by the inadequacy of the population statistical characteristics of these parameters. Previously we simulated ametropic (near- or far-sighted) eyes using three independent variables: the axial length of the eye, the corneal surface curvature, and the intraocular refractive index gradient. The prescription for the correction of an ametropic eye is determined by its second-order coefficients of the wavefront aberrations. These corrections are typically achieved using contact lens, spectacle lens, or laser surgery (LASIK). However, the higher order aberrations, which are not corrected and are likely complicated or enhanced by the lower-order correction, could be important for visual performance in a darkened environment. In this paper, we investigate the higher order wavefront aberrations of synthetic ametropic eyes and compare results with measured data published in the past decade. The behavior of three types of ametropes is discussed.

Genetic correction using engineered nucleases for gene therapy applications.

PubMed

Li, Hongmei Lisa; Nakano, Takao; Hotta, Akitsu

2014-01-01

Genetic mutations in humans are associated with congenital disorders and phenotypic traits. Gene therapy holds the promise to cure such genetic disorders, although it has suffered from several technical limitations for decades. Recent progress in gene editing technology using tailor-made nucleases, such as meganucleases (MNs), zinc finger nucleases (ZFNs), TAL effector nucleases (TALENs) and, more recently, CRISPR/Cas9, has significantly broadened our ability to precisely modify target sites in the human genome. In this review, we summarize recent progress in gene correction approaches of the human genome, with a particular emphasis on the clinical applications of gene therapy. © 2013 The Authors Development, Growth & Differentiation © 2013 Japanese Society of Developmental Biologists.

[Residues of tetracycline and quinolones in wild fish living around a salmon aquaculture center in Chile].

PubMed

Fortt Z, Antonia; Cabello C, Felipe; Buschmann R, Alejandro

2007-02-01

The presence of residues of tetracycline, quinolones and antiparasitic drugs was investigated in wild fish captured around salmon aquaculture pens in Cochamó, Region X, Chile. Residues of both antibiotics were found in the meta [corrected] of two species of wild fish that are consumed by humans, robalo (Elginops maclovinus) and cabrilla (Sebastes capensis) [corrected] These findings suggest that the antibiotic usage in salmon aquaculture in Chile has nvironmental implications that may affect human and animal health. More studies are needed in Chile to determine the relevance of these findings for human and animal health and the environment to regulate this use of antibiotics.

Transport through correlated systems with density functional theory

NASA Astrophysics Data System (ADS)

Kurth, S.; Stefanucci, G.

2017-10-01

We present recent advances in density functional theory (DFT) for applications in the field of quantum transport, with particular emphasis on transport through strongly correlated systems. We review the foundations of the popular Landauer-Büttiker(LB)  +  DFT approach. This formalism, when using approximations to the exchange-correlation (xc) potential with steps at integer occupation, correctly captures the Kondo plateau in the zero bias conductance at zero temperature but completely fails to capture the transition to the Coulomb blockade (CB) regime as the temperature increases. To overcome the limitations of LB  +  DFT, the quantum transport problem is treated from a time-dependent (TD) perspective using TDDFT, an exact framework to deal with nonequilibrium situations. The steady-state limit of TDDFT shows that in addition to an xc potential in the junction, there also exists an xc correction to the applied bias. Open shell molecules in the CB regime provide the most striking examples of the importance of the xc bias correction. Using the Anderson model as guidance we estimate these corrections in the limit of zero bias. For the general case we put forward a steady-state DFT which is based on one-to-one correspondence between the pair of basic variables, steady density on and steady current across the junction and the pair local potential on and bias across the junction. Like TDDFT, this framework also leads to both an xc potential in the junction and an xc correction to the bias. Unlike TDDFT, these potentials are independent of history. We highlight the universal features of both xc potential and xc bias corrections for junctions in the CB regime and provide an accurate parametrization for the Anderson model at arbitrary temperatures and interaction strengths, thus providing a unified DFT description for both Kondo and CB regimes and the transition between them.

Grammatical Pattern Learning by Human Infants and Cotton-Top Tamarin Monkeys

ERIC Educational Resources Information Center

Saffran, Jenny; Hauser, Marc; Seibel, Rebecca; Kapfhamer, Joshua; Tsao, Fritz; Cushman, Fiery

2008-01-01

There is a surprising degree of overlapping structure evident across the languages of the world. One factor leading to cross-linguistic similarities may be constraints on human learning abilities. Linguistic structures that are easier for infants to learn should predominate in human languages. If correct, then (a) human infants should more readily…

40 CFR 280.66 - Corrective action plan.

Code of Federal Regulations, 2011 CFR

2011-07-01

... submitting a plan that provides for adequate protection of human health and the environment as determined by... will adequately protect human health, safety, and the environment. In making this determination, the...

A novel approach for baseline correction in 1H-MRS signals based on ensemble empirical mode decomposition.

PubMed

Parto Dezfouli, Mohammad Ali; Dezfouli, Mohsen Parto; Rad, Hamidreza Saligheh

2014-01-01

Proton magnetic resonance spectroscopy ((1)H-MRS) is a non-invasive diagnostic tool for measuring biochemical changes in the human body. Acquired (1)H-MRS signals may be corrupted due to a wideband baseline signal generated by macromolecules. Recently, several methods have been developed for the correction of such baseline signals, however most of them are not able to estimate baseline in complex overlapped signal. In this study, a novel automatic baseline correction method is proposed for (1)H-MRS spectra based on ensemble empirical mode decomposition (EEMD). This investigation was applied on both the simulated data and the in-vivo (1)H-MRS of human brain signals. Results justify the efficiency of the proposed method to remove the baseline from (1)H-MRS signals.

75 FR 52356 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel: National Human...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-25

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and Control Special Emphasis Panel: National Human Immunodeficiency Virus (HIV) Behavioral Surveillance, Funding Opportunity Announcement PS11-001; Initial Review Correction...

Microscopic lymph node tumor burden quantified by macroscopic dual-tracer molecular imaging

PubMed Central

Tichauer, Kenneth M.; Samkoe, Kimberley S.; Gunn, Jason R.; Kanick, Stephen C.; Hoopes, P. Jack; Barth, Richard J.; Kaufman, Peter A.; Hasan, Tayyaba; Pogue, Brian W.

2014-01-01

Lymph node biopsy (LNB) is employed in many cancer surgeries to identify metastatic disease and stage the cancer, yet morbidity and diagnostic delays associated with LNB could be avoided if non-invasive imaging of nodal involvement was reliable. Molecular imaging has potential in this regard; however, variable delivery and nonspecific uptake of imaging tracers has made conventional approaches ineffective clinically. A method of correcting for non-specific uptake with injection of a second untargeted tracer is presented, allowing tumor burden in lymph nodes to be quantified. The approach was confirmed in an athymic mouse model of metastatic human breast cancer targeting epidermal growth factor receptor, a cell surface receptor overexpressed by many cancers. A significant correlation was observed between in vivo (dual-tracer) and ex vivo measures of tumor burden (r = 0.97, p < 0.01), with an ultimate sensitivity of approximately 200 cells (potentially more sensitive than conventional LNB). PMID:25344739

The NMDA receptor as a target for cognitive enhancement

PubMed Central

Collingridge, Graham L.; Volianskis, Arturas; Bannister, Neil; France, Grace; Hanna, Lydia; Mercier, Marion; Tidball, Patrick; Fang, Guangyu; Irvine, Mark W.; Costa, Blaise M.; Monaghan, Daniel T.; Bortolotto, Zuner A.; Molnár, Elek; Lodge, David; Jane, David E.

2015-01-01

NMDA receptors (NMDAR) play an important role in neural plasticity including long-term potentiation and long-term depression, which are likely to explain their importance for learning and memory. Cognitive decline is a major problem facing an ageing human population, so much so that its reversal has become an important goal for scientific research and pharmaceutical development. Enhancement of NMDAR function is a core strategy toward this goal. In this review we indicate some of the major ways of potentiating NMDAR function by both direct and indirect modulation. There is good evidence that both positive and negative modulation can enhance function suggesting that a subtle approach correcting imbalances in particular clinical situations will be required. Excessive activation and the resultant deleterious effects will need to be carefully avoided. Finally we describe some novel positive allosteric modulators of NMDARs, with some subunit selectivity, and show initial evidence of their ability to affect NMDAR mediated events. PMID:22796429

77 FR 59728 - Airworthiness Directives; The Boeing Company Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-01

... correct installation of certain bonding straps, and applicable corrective actions. This new AD adds... the potential of ignition sources inside fuel tanks in the event of a severe lightning strike, which... installation of certain bonding straps, and applicable corrective actions. That NPRM also proposed to add...

Silent IL2RG Gene Editing in Human Pluripotent Stem Cells.

PubMed

Li, Li B; Ma, Chao; Awong, Geneve; Kennedy, Marion; Gornalusse, German; Keller, Gordon; Kaufman, Dan S; Russell, David W

2016-03-01

Many applications of pluripotent stem cells (PSCs) require efficient editing of silent chromosomal genes. Here, we show that a major limitation in isolating edited clones is silencing of the selectable marker cassette after homologous recombination and that this can be overcome by using a ubiquitous chromatin opening element (UCOE) promoter-driven transgene. We use this strategy to edit the silent IL2RG locus in human PSCs with a recombinant adeno-associated virus (rAAV)-targeting vector in the absence of potentially genotoxic, site-specific nucleases and show that IL2RG is required for natural killer and T-cell differentiation of human PSCs. Insertion of an active UCOE promoter into a silent locus altered the histone modification and cytosine methylation pattern of surrounding chromatin, but these changes resolved when the UCOE promoter was removed. This same approach could be used to correct IL2RG mutations in X-linked severe combined immunodeficiency patient-derived induced PSCs (iPSCs), to prevent graft versus host disease in regenerative medicine applications, or to edit other silent genes.

The high cost of the international aging prisoner crisis: well-being as the common denominator for action.

PubMed

Maschi, Tina; Viola, Deborah; Sun, Fei

2013-08-01

The aging prisoner crisis continues to gain international attention as the high human, social, and economic costs of warehousing older adults with complex physical, mental health, and social care needs in prison continues to rise. According to the United Nations, older adults and the serious and terminally ill are considered special needs populations subject to special international health and social practice and policy considerations. We argue that older adults in prison have unique individual and social developmental needs that result from life course exposure to cumulative risk factors compounded by prison conditions that accelerate their aging. We position these factors in a social context model of human development and well-being and present a review of international human rights guidelines that pertain to promoting health and well-being to those aging in custody. The study concludes with promising practices and recommendations of their potential to reduce the high direct and indirect economic costs associated with mass confinement of older adults, many of whom need specialized long-term care that global correctional systems are inadequately equipped to provide.

A novel behavioral paradigm for assessing concept of nests in mice

PubMed Central

Kuang, Hui; Mei, Bing; Cui, Zhenzhong; Lin, Longnian; Tsien, Joe Z.

2013-01-01

Abstract concepts in the brain enable humans to efficiently and correctly recognize and categorize a seemingly infinite amount of objects and daily events. Such abstract generalization abilities are traditionally considered to be unique to humans and perhaps non-human primates. However, emerging neurophysiological recordings indicate the existence of neural correlates for the abstract concept of nests in the mouse brain. To facilitate the molecular and genetic analyses of concepts in the mouse model, we have developed a nest generalization test based on mice’s natural behavior. We show that inducible and forebrain-specific NMDA receptor knockout results in pronounced impairment in this test. Interestingly, this generalization deficit could be gradually compensated for over time by repeated experiences even in face of the continued deficit in object recognition memory. On the contrast, the forebrain-specific presenilin-1 knockout mice, which have subtle phenotypes, were normal in performing this test. Therefore, our study not only establishes a quantitative method for assessing the nest concept in mice, but also demonstrates its great potential in combining powerful mouse genetics for dissecting the molecular basis of concept formation in the brain. PMID:20350568

A PITX3-EGFP Reporter Line Reveals Connectivity of Dopamine and Non-dopamine Neuronal Subtypes in Grafts Generated from Human Embryonic Stem Cells.

PubMed

Niclis, Jonathan C; Gantner, Carlos W; Hunt, Cameron P J; Kauhausen, Jessica A; Durnall, Jennifer C; Haynes, John M; Pouton, Colin W; Parish, Clare L; Thompson, Lachlan H

2017-09-12

Development of safe and effective stem cell-based therapies for brain repair requires an in-depth understanding of the in vivo properties of neural grafts generated from human stem cells. Replacing dopamine neurons in Parkinson's disease remains one of the most anticipated applications. Here, we have used a human PITX3-EGFP embryonic stem cell line to characterize the connectivity of stem cell-derived midbrain dopamine neurons in the dopamine-depleted host brain with an unprecedented level of specificity. The results show that the major A9 and A10 subclasses of implanted dopamine neurons innervate multiple, developmentally appropriate host targets but also that the majority of graft-derived connectivity is non-dopaminergic. These findings highlight the promise of stem cell-based procedures for anatomically correct reconstruction of specific neuronal pathways but also emphasize the scope for further refinement in order to limit the inclusion of uncharacterized and potentially unwanted cell types. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Human figure drawings in the evaluation of severe adolescent suicidal behavior.

PubMed

Zalsman, G; Netanel, R; Fischel, T; Freudenstein, O; Landau, E; Orbach, I; Weizman, A; Pfeffer, C R; Apter, A

2000-08-01

To evaluate the reliability of using certain indicators derived from human figure drawings to distinguish between suicidal and nonsuicidal adolescents. Ninety consecutive admissions to an adolescent inpatient unit were assessed. Thirty-nine patients were admitted because of suicidal behavior and 51 for other reasons. All subjects were given the Human Figure Drawing (HFD) test. HFD was evaluated according to the method of Pfeffer and Richman, and the degree of suicidal behavior was rated by the Child Suicide Potential Scale. The internal reliability was satisfactory. HFD indicators correlated significantly with quantitative measures of suicidal behavior; of these indicators specifically, overall impression of the evaluator enabled the prediction of suicidal behavior and the distinction between suicidal and nonsuicidal inpatients (p < .001). A group of graphic indicators derived from a discriminant analysis formed a function, which was able to identify 84.6% of the suicidal and 76.6% of the nonsuicidal adolescents correctly. Many of the items had a regressive quality. The HFD is an example of a simple projective test that may have empirical reliability. It may be useful for the assessment of severe suicidal behavior in adolescents.

Manipulation of Pre-Target Activity on the Right Frontal Eye Field Enhances Conscious Visual Perception in Humans

PubMed Central

Chanes, Lorena; Chica, Ana B.; Quentin, Romain; Valero-Cabré, Antoni

2012-01-01

The right Frontal Eye Field (FEF) is a region of the human brain, which has been consistently involved in visuo-spatial attention and access to consciousness. Nonetheless, the extent of this cortical site’s ability to influence specific aspects of visual performance remains debated. We hereby manipulated pre-target activity on the right FEF and explored its influence on the detection and categorization of low-contrast near-threshold visual stimuli. Our data show that pre-target frontal neurostimulation has the potential when used alone to induce enhancements of conscious visual detection. More interestingly, when FEF stimulation was combined with visuo-spatial cues, improvements remained present only for trials in which the cue correctly predicted the location of the subsequent target. Our data provide evidence for the causal role of the right FEF pre-target activity in the modulation of human conscious vision and reveal the dependence of such neurostimulatory effects on the state of activity set up by cue validity in the dorsal attentional orienting network. PMID:22615759

The NMDA receptor partial agonist d-cycloserine does not enhance motor learning.

PubMed

Günthner, Jan; Scholl, Jacqueline; Favaron, Elisa; Harmer, Catherine J; Johansen-Berg, Heidi; Reinecke, Andrea

2016-10-01

There has recently been increasing interest in pharmacological manipulations that could potentially enhance exposure-based cognitive behaviour therapy for anxiety disorders. One such medication is the partial NMDA agonist d-cycloserine. It has been suggested that d-cycloserine enhances cognitive behaviour therapy by making learning faster. While animal studies have supported this view of the drug accelerating learning, evidence in human studies has been mixed. We therefore designed an experiment to measure the effects of d-cycloserine on human motor learning. Fifty-four healthy human volunteers were randomly assigned to a single dose of 250mg d-cycloserine versus placebo in a double-blind design. They then performed a motor sequence learning task. D-cycloserine did not increase the speed of motor learning or the overall amount learnt. However, we noted that participants on d-cycloserine tended to respond more carefully (shifting towards slower, but more correct responses). The results suggest that d-cycloserine does not exert beneficial effects on psychological treatments via mechanisms involved in motor learning. Further studies are needed to clarify the influence on other cognitive mechanisms. © The Author(s) 2016.

Scalable topographies to support proliferation and Oct4 expression by human induced pluripotent stem cells

PubMed Central

Reimer, Andreas; Vasilevich, Aliaksei; Hulshof, Frits; Viswanathan, Priyalakshmi; van Blitterswijk, Clemens A.; de Boer, Jan; Watt, Fiona M.

2016-01-01

It is well established that topographical features modulate cell behaviour, including cell morphology, proliferation and differentiation. To define the effects of topography on human induced pluripotent stem cells (iPSC), we plated cells on a topographical library containing over 1000 different features in medium lacking animal products (xeno-free). Using high content imaging, we determined the effect of each topography on cell proliferation and expression of the pluripotency marker Oct4 24 h after seeding. Features that maintained Oct4 expression also supported proliferation and cell-cell adhesion at 24 h, and by 4 days colonies of Oct4-positive, Sox2-positive cells had formed. Computational analysis revealed that small feature size was the most important determinant of pluripotency, followed by high wave number and high feature density. Using this information we correctly predicted whether any given topography within our library would support the pluripotent state at 24 h. This approach not only facilitates the design of substrates for optimal human iPSC expansion, but also, potentially, identification of topographies with other desirable characteristics, such as promoting differentiation. PMID:26757610

Scalable topographies to support proliferation and Oct4 expression by human induced pluripotent stem cells.

PubMed

Reimer, Andreas; Vasilevich, Aliaksei; Hulshof, Frits; Viswanathan, Priyalakshmi; van Blitterswijk, Clemens A; de Boer, Jan; Watt, Fiona M

2016-01-13

It is well established that topographical features modulate cell behaviour, including cell morphology, proliferation and differentiation. To define the effects of topography on human induced pluripotent stem cells (iPSC), we plated cells on a topographical library containing over 1000 different features in medium lacking animal products (xeno-free). Using high content imaging, we determined the effect of each topography on cell proliferation and expression of the pluripotency marker Oct4 24 h after seeding. Features that maintained Oct4 expression also supported proliferation and cell-cell adhesion at 24 h, and by 4 days colonies of Oct4-positive, Sox2-positive cells had formed. Computational analysis revealed that small feature size was the most important determinant of pluripotency, followed by high wave number and high feature density. Using this information we correctly predicted whether any given topography within our library would support the pluripotent state at 24 h. This approach not only facilitates the design of substrates for optimal human iPSC expansion, but also, potentially, identification of topographies with other desirable characteristics, such as promoting differentiation.

[Correction of the human body hydration in different periods of space flight].

PubMed

Noskov, V B

2003-01-01

Hydration level of the human body at the end of space flight is not same as at its beginning. This was the reason for development and testing of opposite in action methods for hydration improvement: at the onset of microgravity a dehydration therapy is applied and, on the contrary, in the final period of space flight methods for retaining body fluids are of preference. Consumption of a diuretic and a water-salt supplement by orbiting crews reached the required effect suggesting applicability of the pharmaceutical correction as a measure against dehydration.

45 CFR 400.49 - Recovery of overpayments and correction of underpayments.

Code of Federal Regulations, 2010 CFR

2010-10-01

... underpayments. 400.49 Section 400.49 Public Welfare Regulations Relating to Public Welfare OFFICE OF REFUGEE RESETTLEMENT, ADMINISTRATION FOR CHILDREN AND FAMILIES, DEPARTMENT OF HEALTH AND HUMAN SERVICES REFUGEE RESETTLEMENT PROGRAM Refugee Cash Assistance § 400.49 Recovery of overpayments and correction of underpayments...

77 FR 76049 - Draft Guidance for Industry on Electronic Source Data in Clinical Investigations; Correction

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-26

..., Office of Planning & Informatics, Center for Drug Evaluation and Research, Food and Drug Administration... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-D-0643...: Food and Drug Administration, HHS. ACTION: Notice; correction. [[Page 76050

75 FR 81612 - Findings of Misconduct in Science; Correction

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-28

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Office of the Secretary Findings of Misconduct in Science... Misconduct in Science.'' DATES: Effective Date: December 28, 2010. Applicability Date: The correction notice is applicable for the Findings of Misconduct in Science notice published on November 29, 2010. FOR...

Handouts for the Resource Conservation and Recovery Act (RCRA) Corrective Action Training Strategies for Meeting the 2020 Vision

EPA Pesticide Factsheets

Materials for course intended to develop and enhance the skills of qualified personnel who will implement corrective actions for their sites by the year 2020 that are protective of human health and the environment while encouraging revitalization.

78 FR 59706 - Secure Supply Chain Pilot Program; Correction

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-27

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2008-N-0656...,'' in the third full paragraph, the sentence that reads ``For communications other than the submission....hhs.gov '' is corrected to read ``For communications other than the submission of the SSCPP...

Loop quantum corrected Einstein Yang-Mills black holes

NASA Astrophysics Data System (ADS)

Protter, Mason; DeBenedictis, Andrew

2018-05-01

In this paper, we study the homogeneous interiors of black holes possessing SU(2) Yang-Mills fields subject to corrections inspired by loop quantum gravity. The systems studied possess both magnetic and induced electric Yang-Mills fields. We consider the system of equations both with and without Wilson loop corrections to the Yang-Mills potential. The structure of the Yang-Mills Hamiltonian, along with the restriction to homogeneity, allows for an anomaly-free effective quantization. In particular, we study the bounce which replaces the classical singularity and the behavior of the Yang-Mills fields in the quantum corrected interior, which possesses topology R ×S2 . Beyond the bounce, the magnitude of the Yang-Mills electric field asymptotically grows monotonically. This results in an ever-expanding R sector even though the two-sphere volume is asymptotically constant. The results are similar with and without Wilson loop corrections on the Yang-Mills potential.

Correctional officers' perceptions of a solution-focused training program: potential implications for working with offenders.

PubMed

Pan, Peter Jen Der; Deng, Liang-Yu F; Chang, Shona Shih Hua; Jiang, Karen Jye-Ru

2011-09-01

The purpose of this exploratory study was to explore correctional officers' perceptions and experiences during a solution-focused training program and to initiate development of a modified pattern for correctional officers to use in jails. The study uses grounded theory procedures combined with a follow-up survey. The findings identified six emergent themes: obstacles to doing counseling work in prisons, offenders' amenability to change, correctional officers' self-image, advantages of a solution-focused approach (SFA), potential advantages of applying SFA to offenders, and the need for the consolidation of learning and transformation. Participants perceived the use of solution-focused techniques as appropriate, important, functional, and of only moderate difficulty in interacting with offenders. Finally, a modified pattern was developed for officers to use when working with offenders in jails. Suggestions and recommendations are made for correctional interventions and future studies.

Atomic electron energies including relativistic effects and quantum electrodynamic corrections

NASA Technical Reports Server (NTRS)

Aoyagi, M.; Chen, M. H.; Crasemann, B.; Huang, K. N.; Mark, H.

1977-01-01

Atomic electron energies have been calculated relativistically. Hartree-Fock-Slater wave functions served as zeroth-order eigenfunctions to compute the expectation of the total Hamiltonian. A first order correction to the local approximation was thus included. Quantum-electrodynamic corrections were made. For all orbitals in all atoms with 2 less than or equal to Z less than or equal to 106, the following quantities are listed: total energies, electron kinetic energies, electron-nucleus potential energies, electron-electron potential energies consisting of electrostatic and Breit interaction (magnetic and retardation) terms, and vacuum polarization energies. These results will serve for detailed comparison of calculations based on other approaches. The magnitude of quantum electrodynamic corrections is exhibited quantitatively for each state.

Scattering properties of ultrafast laser-induced refractive index shaping lenticular structures in hydrogels

NASA Astrophysics Data System (ADS)

Wozniak, Kaitlin T.; Germer, Thomas A.; Butler, Sam C.; Brooks, Daniel R.; Huxlin, Krystel R.; Ellis, Jonathan D.

2018-02-01

We present measurements of light scatter induced by a new ultrafast laser technique being developed for laser refractive correction in transparent ophthalmic materials such as cornea, contact lenses, and/or intraocular lenses. In this new technique, called intra-tissue refractive index shaping (IRIS), a 405 nm femtosecond laser is focused and scanned below the corneal surface, inducing a spatially-varying refractive index change that corrects vision errors. In contrast with traditional laser correction techniques, such as laser in-situ keratomileusis (LASIK) or photorefractive keratectomy (PRK), IRIS does not operate via photoablation, but rather changes the refractive index of transparent materials such as cornea and hydrogels. A concern with any laser eye correction technique is additional scatter induced by the process, which can adversely affect vision, especially at night. The goal of this investigation is to identify sources of scatter induced by IRIS and to mitigate possible effects on visual performance in ophthalmic applications. Preliminary light scattering measurements on patterns written into hydrogel showed four sources of scatter, differentiated by distinct behaviors: (1) scattering from scanned lines; (2) scattering from stitching errors, resulting from adjacent scanning fields not being aligned to one another; (3) diffraction from Fresnel zone discontinuities; and (4) long-period variations in the scans that created distinct diffraction peaks, likely due to inconsistent line spacing in the writing instrument. By knowing the nature of these different scattering errors, it will now be possible to modify and optimize the design of IRIS structures to mitigate potential deficits in visual performance in human clinical trials.

Experience-based human perception of facial expressions in Barbary macaques (Macaca sylvanus)

PubMed Central

Levy, Xandria; Meints, Kerstin; Majolo, Bonaventura

2017-01-01

Background Facial expressions convey key cues of human emotions, and may also be important for interspecies interactions. The universality hypothesis suggests that six basic emotions (anger, disgust, fear, happiness, sadness, and surprise) should be expressed by similar facial expressions in close phylogenetic species such as humans and nonhuman primates. However, some facial expressions have been shown to differ in meaning between humans and nonhuman primates like macaques. This ambiguity in signalling emotion can lead to an increased risk of aggression and injuries for both humans and animals. This raises serious concerns for activities such as wildlife tourism where humans closely interact with wild animals. Understanding what factors (i.e., experience and type of emotion) affect ability to recognise emotional state of nonhuman primates, based on their facial expressions, can enable us to test the validity of the universality hypothesis, as well as reduce the risk of aggression and potential injuries in wildlife tourism. Methods The present study investigated whether different levels of experience of Barbary macaques, Macaca sylvanus, affect the ability to correctly assess different facial expressions related to aggressive, distressed, friendly or neutral states, using an online questionnaire. Participants’ level of experience was defined as either: (1) naïve: never worked with nonhuman primates and never or rarely encountered live Barbary macaques; (2) exposed: shown pictures of the different Barbary macaques’ facial expressions along with the description and the corresponding emotion prior to undertaking the questionnaire; (3) expert: worked with Barbary macaques for at least two months. Results Experience with Barbary macaques was associated with better performance in judging their emotional state. Simple exposure to pictures of macaques’ facial expressions improved the ability of inexperienced participants to better discriminate neutral and distressed faces, and a trend was found for aggressive faces. However, these participants, even when previously exposed to pictures, had difficulties in recognising aggressive, distressed and friendly faces above chance level. Discussion These results do not support the universality hypothesis as exposed and naïve participants had difficulties in correctly identifying aggressive, distressed and friendly faces. Exposure to facial expressions improved their correct recognition. In addition, the findings suggest that providing simple exposure to 2D pictures (for example, information signs explaining animals’ facial signalling in zoos or animal parks) is not a sufficient educational tool to reduce tourists’ misinterpretations of macaque emotion. Additional measures, such as keeping a safe distance between tourists and wild animals, as well as reinforcing learning via videos or supervised visits led by expert guides, could reduce such issues and improve both animal welfare and tourist experience. PMID:28584731

The Potential of Automated Corrective Feedback to Remediate Cohesion Problems in Advanced Students' Writing

ERIC Educational Resources Information Center

Strobl, Carola

2017-01-01

This study explores the potential of a feedback environment using simple string-based pattern matching technology for the provision of automated corrective feedback on cohesion problems. Thirty-eight high-frequent problems, including non-target like use of connectives and co-references were addressed providing both direct and indirect feedback.…

Characterization of nasal potential difference in cftr knockout and F508del-CFTR mice.

PubMed

Saussereau, Emilie Lyne; Roussel, Delphine; Diallo, Siradiou; Debarbieux, Laurent; Edelman, Aleksander; Sermet-Gaudelus, Isabelle

2013-01-01

Treatments designed to correct cystic fibrosis transmembrane conductance regulator (CFTR) defects must first be evaluated in preclinical experiments in the mouse model of cystic fibrosis (CF). Mice nasal mucosa mimics the bioelectric defect seen in humans. The use of nasal potential difference (V(TE)) to assess ionic transport is a powerful test evaluating the restoration of CFTR function. Nasal V(TE) in CF mice must be well characterized for correct interpretation. We performed V(TE) measurements in large-scale studies of two mouse models of CF--B6;129 cftr knockout and FVB F508del-CFTR--and their respective wild-type (WT) littermates. We assessed the repeatability of the test for cftr knockout mice and defined cutoff points distinguishing between WT and F508del-CFTR mice. We determined the typical V(TE) values for CF and WT mice and demonstrated the existence of residual CFTR activity in F508del-CFTR mice. We characterized intra-animal variability in B6;129 mice and defined the cutoff points for F508del-CFTR chloride secretion rescue. Hyperpolarization of more than -2.15 mV after perfusion with a low-concentration Cl(-) solution was considered to indicate a normal response. These data will make it possible to interpret changes in nasal V(TE) in mouse models of CF, in future preclinical studies.

Soft Tissue Repair with Easy-Accessible Autologous Newborn Placenta or Umbilical Cord Blood in Severe Malformations: A Primary Evaluation

PubMed Central

2017-01-01

Disrupted organogenesis leads to permanent malformations that may require surgical correction. Autologous tissue grafts may be needed in severe lack of orthotopic tissue but include donor site morbidity. The placenta is commonly discarded after birth and has a therapeutic potential. The aim of this study was to determine if the amnion from placenta or plasma rich of growth factors (PRGF) with mononuclear cells (MNC) from umbilical cord blood (UCB), collected noninvasively, could be used as bio-constructs for autologous transplantation as an easy-accessible no cell culture-required method. Human amnion and PRGF gel were isolated and kept in culture for up to 21 days with or without small intestine submucosa (SIS). The cells in the constructs showed a robust phenotype without induced increased proliferation (Ki67) or apoptosis (caspase 3), but the constructs showed decreased integrity of the amnion-epithelial layer at the end of culture. Amnion-residing cells in the SIS constructs expressed CD73 or pan-cytokeratin, and cells in the PRGF-SIS constructs expressed CD45 and CD34. This study shows that amnion and UCB are potential sources for production of autologous grafts in the correction of congenital soft tissue defects. The constructs can be made promptly after birth with minimal handling or cell expansion needed. PMID:29403534

Time delay of critical images in the vicinity of cusp point of gravitational-lens systems

NASA Astrophysics Data System (ADS)

Alexandrov, A.; Zhdanov, V.

2016-12-01

We consider approximate analytical formulas for time-delays of critical images of a point source in the neighborhood of a cusp-caustic. We discuss zero, first and second approximations in powers of a parameter that defines the proximity of the source to the cusp. These formulas link the time delay with characteristics of the lens potential. The formula of zero approximation was obtained by Congdon, Keeton & Nordgren (MNRAS, 2008). In case of a general lens potential we derived first order correction thereto. If the potential is symmetric with respect to the cusp axis, then this correction is identically equal to zero. For this case, we obtained second order correction. The relations found are illustrated by a simple model example.

Closure Report for Corrective Action Unit 539: Areas 25 and 26 Railroad Tracks Nevada National Security Site, Nevada with ROTC-1, Revision 0

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

Mark Kauss

2011-06-01

This Closure Report (CR) presents information supporting the closure of Corrective Action Unit (CAU) 539: Areas 25 and 26 Railroad Tracks, Nevada National Security Site, Nevada. This CR complies with the requirements of the Federal Facility Agreement and Consent Order (FFACO) that was agreed to by the State of Nevada; U.S. Department of Energy (DOE), Environmental Management; U.S. Department of Defense; and DOE, Legacy Management. The corrective action sites (CASs) within CAU 539 are located within Areas 25 and 26 of the Nevada National Security Site. Corrective Action Unit 539 comprises the following CASs: • 25-99-21, Area 25 Railroad Tracksmore » • 26-99-05, Area 26 Railroad Tracks The purpose of this CR is to provide documentation supporting the completed corrective actions and provide data confirming that the closure objectives for CASs within CAU 539 were met. To achieve this, the following actions were performed: • Reviewed documentation on historical and current site conditions, including the concentration and extent of contamination. • Conducted radiological walkover surveys of railroad tracks in both Areas 25 and 26. • Collected ballast and soil samples and calculated internal dose estimates for radiological releases. • Collected in situ thermoluminescent dosimeter measurements and calculated external dose estimates for radiological releases. • Removed lead bricks as potential source material (PSM) and collected verification samples. • Implemented corrective actions as necessary to protect human health and the environment. • Properly disposed of corrective action and investigation wastes. • Implemented an FFACO use restriction (UR) for radiological contamination at CAS 25-99-21. The approved UR form and map are provided in Appendix F and will be filed in the DOE, National Nuclear Security Administration Nevada Site Office (NNSA/NSO), Facility Information Management System; the FFACO database; and the NNSA/NSO CAU/CAS files. From November 29, 2010, through May 2, 2011, closure activities were performed as set forth in the Streamlined Approach for Environmental Restoration (SAFER) Plan for Corrective Action Unit 539: Areas 25 and 26 Railroad Tracks, Nevada Test Site, Nevada. The purposes of the activities as defined during the data quality objectives process were as follows: • Determine whether contaminants of concern (COCs) are present. • If COCs are present, determine their nature and extent, implement appropriate corrective actions, and properly dispose of wastes. Analytes detected during the closure activities were evaluated against final action levels (FALs) to determine COCs for CAU 539. Assessment of the data generated from closure activities revealed the following: • At CAS 26-99-05, the total effective dose for radiological releases did not exceed the FAL of 25 millirem per Industrial Area year. Potential source material in the form of lead bricks was found at three locations. A corrective action of clean closure was implemented at these locations, and verification samples indicated that no further action is necessary. • At CAS 25-99-21, the total effective dose for radiological releases exceeds the FAL of 25 millirem per Industrial Area year. Potential source material in the form of lead bricks was found at eight locations. A corrective action was implemented by removing the lead bricks and soil above FALs at these locations, and verification samples indicated that no further action is necessary. Pieces of debris with high radioactivity were identified as PSM and remain within the CAS boundary. A corrective action of closure in place with a UR was implemented at this CAS because closure activities showed evidence of remaining soil contamination and radioactive PSM. Future land use will be restricted from surface and intrusive activities. Closure activities generated waste streams consisting of industrial solid waste, recyclable materials, low-level radioactive waste, and mixed low-level radioactive waste. Wastes were disposed of in the appropriate onsite landfills. The NNSA/NSO provides the following recommendations: • Clean closure is required at CAS 26-99-05. • Closure in place is required at CAS 25-99-21. • A UR is required at CAS 25-99-21. • A Notice of Completion to the NNSA/NSO is requested from the Nevada Division of Environmental Protection for closure of CAU 539. • Corrective Action Unit 539 should be moved from Appendix III to Appendix IV of the FFACO.« less

Spatial Resolution Requirements for Accurate Identification of Drivers of Atrial Fibrillation

PubMed Central

Roney, Caroline H.; Cantwell, Chris D.; Bayer, Jason D.; Qureshi, Norman A.; Lim, Phang Boon; Tweedy, Jennifer H.; Kanagaratnam, Prapa; Vigmond, Edward J.; Ng, Fu Siong

2017-01-01

Background— Recent studies have demonstrated conflicting mechanisms underlying atrial fibrillation (AF), with the spatial resolution of data often cited as a potential reason for the disagreement. The purpose of this study was to investigate whether the variation in spatial resolution of mapping may lead to misinterpretation of the underlying mechanism in persistent AF. Methods and Results— Simulations of rotors and focal sources were performed to estimate the minimum number of recording points required to correctly identify the underlying AF mechanism. The effects of different data types (action potentials and unipolar or bipolar electrograms) and rotor stability on resolution requirements were investigated. We also determined the ability of clinically used endocardial catheters to identify AF mechanisms using clinically recorded and simulated data. The spatial resolution required for correct identification of rotors and focal sources is a linear function of spatial wavelength (the distance between wavefronts) of the arrhythmia. Rotor localization errors are larger for electrogram data than for action potential data. Stationary rotors are more reliably identified compared with meandering trajectories, for any given spatial resolution. All clinical high-resolution multipolar catheters are of sufficient resolution to accurately detect and track rotors when placed over the rotor core although the low-resolution basket catheter is prone to false detections and may incorrectly identify rotors that are not present. Conclusions— The spatial resolution of AF data can significantly affect the interpretation of the underlying AF mechanism. Therefore, the interpretation of human AF data must be taken in the context of the spatial resolution of the recordings. PMID:28500175

Potential health effects of gasoline and its constituents: A review of current literature (1990-1997) on toxicological data.

PubMed Central

Caprino, L; Togna, G I

1998-01-01

We reviewed toxicological studies, both experimental and epidemiological, that appeared in international literature in the period 1990-1997 and included both leaded and unleaded gasolines as well as their components and additives. The aim of this overview was to select, arrange, and present references of scientific papers published during the period under consideration and to summarize the data in order to give a comprehensive picture of the results of toxicological studies performed in laboratory animals (including carcinogenic, teratogenic, or embryotoxic activity), mutagenicity and genotoxic aspects in mammalian and bacterial systems, and epidemiological results obtained in humans in relation to gasoline exposure. This paper draws attention to the inherent difficulties in assessing with precision any potential adverse effects on health, that is, the risk of possible damage to man and his environment from gasoline. The difficulty of risk assessment still exists despite the fact that the studies examined are definitely more technically valid than those of earlier years. The uncertainty in overall risk determination from gasoline exposure also derives from the conflicting results of different studies, from the lack of a correct scientific approach in some studies, from the variable characteristics of the different gasoline mixtures, and from the difficulties of correctly handling potentially confounding variables related to lifestyle (e.g., cigarette smoking, drug use) or to preexisting pathological conditions. In this respect, this paper highlights the need for accurately assessing the conclusive explanations reported in scientific papers so as to avoid the spread of inaccurate or misleading information on gasoline toxicity in nonscientific papers and in mass-media messages. PMID:9452413

Failure mode and effect analysis: improving intensive care unit risk management processes.

PubMed

Askari, Roohollah; Shafii, Milad; Rafiei, Sima; Abolhassani, Mohammad Sadegh; Salarikhah, Elaheh

2017-04-18

Purpose Failure modes and effects analysis (FMEA) is a practical tool to evaluate risks, discover failures in a proactive manner and propose corrective actions to reduce or eliminate potential risks. The purpose of this paper is to apply FMEA technique to examine the hazards associated with the process of service delivery in intensive care unit (ICU) of a tertiary hospital in Yazd, Iran. Design/methodology/approach This was a before-after study conducted between March 2013 and December 2014. By forming a FMEA team, all potential hazards associated with ICU services - their frequency and severity - were identified. Then risk priority number was calculated for each activity as an indicator representing high priority areas that need special attention and resource allocation. Findings Eight failure modes with highest priority scores including endotracheal tube defect, wrong placement of endotracheal tube, EVD interface, aspiration failure during suctioning, chest tube failure, tissue injury and deep vein thrombosis were selected for improvement. Findings affirmed that improvement strategies were generally satisfying and significantly decreased total failures. Practical implications Application of FMEA in ICUs proved to be effective in proactively decreasing the risk of failures and corrected the control measures up to acceptable levels in all eight areas of function. Originality/value Using a prospective risk assessment approach, such as FMEA, could be beneficial in dealing with potential failures through proposing preventive actions in a proactive manner. The method could be used as a tool for healthcare continuous quality improvement so that the method identifies both systemic and human errors, and offers practical advice to deal effectively with them.

The assessment of electrophysiological activity in human-induced pluripotent stem cell-derived cardiomyocytes exposed to dimethyl sulfoxide and ethanol by manual patch clamp and multi-electrode array system.

PubMed

Hyun, Soo-Wang; Kim, Bo-Ram; Hyun, Sung-Ae; Seo, Joung-Wook

2017-09-01

Recently, electrophysiological activity has been effectively measured in human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) to predict drug-induced arrhythmia. Dimethyl sulfoxide (DMSO) and ethanol have been used as diluting agents in many experiments. However, the maximum DMSO and ethanol concentrations that can be effectively used in the measurement of electrophysiological parameters in hiPSC-CMs-based patch clamp and multi-electrode array (MEA) have not been fully elucidated. We investigated the effects of varying concentrations of DMSO and ethanol used as diluting agents on several electrophysiological parameters in hiPSC-CMs using patch clamp and MEA. Both DMSO and ethanol at concentrations>1% in external solution resulted in osmolality >400mOsmol/kg, but pH was not affected by either agent. Neither DMSO nor ethanol led to cell death at the concentrations examined. However, resting membrane potential, action potential amplitude, action potential duration at 90% and 40%, and corrected field potential duration were decreased significantly at 1% ethanol concentration. DMSO at 1% also significantly decreased the sodium spike amplitude. In addition, the waveform of action potential and field potential was recorded as irregular at 3% concentrations of both DMSO and ethanol. Concentrations of up to 0.3% of either agent did not affect osmolality, pH, cell death, or electrophysiological parameters in hiPSC-CMs. Our findings suggest that 0.3% is the maximum concentration at which DMSO or ethanol should be used for dilution purposes in hiPSC-CMs-based patch clamp and MEA. Copyright © 2017 Elsevier Inc. All rights reserved.

Visual development of human milk-fed preterm infants provided with extra energy and nutrients after hospital discharge.

PubMed

O'Connor, Deborah L; Weishuhn, Karen; Rovet, Joanne; Mirabella, Giuseppe; Jefferies, Ann; Campbell, Douglas M; Asztalos, Elizabeth; Feldman, Mark; Whyte, Hilary; Westall, Carol

2012-05-01

Human milk (HM) is the optimal way to nourish preterm low birth weight (LBW) infants after hospital discharge. However, there are few data on which to assess whether HM alone is sufficient to address hospital-acquired nutrition deficits, and no adequately powered studies have examined this question using neurodevelopment as an outcome. The purpose of this work was to determine whether adding extra energy and nutrients to the feedings of predominantly HM-fed LBW infants early after discharge improves their visual development. Visual development was used in this study as a surrogate marker for neurodevelopment. At discharge, 39 predominantly HM-fed LBW infants (750-1800 g, 1288 ± 288 g) were randomized to receive human milk alone (control) or around half of the HM received daily mixed with a multinutrient fortifier (intervention) for 12 weeks. Grating acuity (ie, visual acuity) and contrast sensitivity were assessed using sweep visual-evoked potential tests at 4 and 6 months corrected age. At 4 and 6 months corrected age, intervention infants demonstrated higher grating acuity compared to those in the control group (intervention: 7.8 ± 1.3 and 9.7 ± 1.2 [cycles/degree] vs control 6.9 ± 1.2 and 8.2 ± 1.3, P = .02). Differences in contrast sensitivity did not reach statistical significance (P = .11). Adding a multinutrient fortifier to a portion of the expressed breast milk provided to predominantly HM-fed LBW infants early after discharge improves their early visual development. Whether these subtle differences in visual development apply to other aspects of development or longer term neurodevelopment are worthy of future investigation.

45 CFR 1303.11 - Suspension on notice and opportunity to show cause.

Code of Federal Regulations, 2010 CFR

2010-10-01

... HUMAN DEVELOPMENT SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES THE ADMINISTRATION FOR CHILDREN... her own initiative or upon a satisfactory showing that the grantee has adequately corrected the...

Ecology and Ethics: Some Relationships for Nature Conservation

NASA Astrophysics Data System (ADS)

Abedi-Sarvestani, Ahmad; Shahvali, Mansoor

These days, the reality of environmental crises creates grave doubts about the future of the natural environment. Many believe that if present human behavior toward the natural environment continues, there will be no hope for a sustainable life. Therefore, it is vital that human behavior toward nature be modified and corrected. Although, ethic is traditionally concerned about relations between individuals, but it is getting more attention for modifying human behavior in order to correct human-nature interaction and establish a well-intentioned one. In this respect, we need science of ecology and ethics together. Ecology helps us to understand natural ecosystems and respective regulations and laws, whereas ethics teach us how to define right and wrong behaviors toward the natural environment. This research discusses some possible relationships that might exist between ecology and ethics toward nature conservation.

Coarse-grained modeling of polyethylene melts: Effect on dynamics

DOE PAGES

Peters, Brandon L.; Salerno, K. Michael; Agrawal, Anupriya; ...

2017-05-23

The distinctive viscoelastic behavior of polymers results from a coupled interplay of motion on multiple length and time scales. Capturing the broad time and length scales of polymer motion remains a challenge. Using polyethylene (PE) as a model macromolecule, we construct coarse-grained (CG) models of PE with three to six methyl groups per CG bead and probe two critical aspects of the technique: pressure corrections required after iterative Boltzmann inversion (IBI) to generate CG potentials that match the pressure of reference fully atomistic melt simulations and the transferability of CG potentials across temperatures. While IBI produces nonbonded pair potentials thatmore » give excellent agreement between the atomistic and CG pair correlation functions, the resulting pressure for the CG models is large compared with the pressure of the atomistic system. We find that correcting the potential to match the reference pressure leads to nonbonded interactions with much deeper minima and slightly smaller effective bead diameter. However, simulations with potentials generated by IBI and pressure-corrected IBI result in similar mean-square displacements (MSDs) and stress autocorrelation functions G( t) for PE melts. While the time rescaling factor required to match CG and atomistic models is the same for pressure- and non-pressure-corrected CG models, it strongly depends on temperature. Furthermore, transferability was investigated by comparing the MSDs and stress autocorrelation functions for potentials developed at different temperatures.« less

Coarse-grained modeling of polyethylene melts: Effect on dynamics

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

Peters, Brandon L.; Salerno, K. Michael; Agrawal, Anupriya

The distinctive viscoelastic behavior of polymers results from a coupled interplay of motion on multiple length and time scales. Capturing the broad time and length scales of polymer motion remains a challenge. Using polyethylene (PE) as a model macromolecule, we construct coarse-grained (CG) models of PE with three to six methyl groups per CG bead and probe two critical aspects of the technique: pressure corrections required after iterative Boltzmann inversion (IBI) to generate CG potentials that match the pressure of reference fully atomistic melt simulations and the transferability of CG potentials across temperatures. While IBI produces nonbonded pair potentials thatmore » give excellent agreement between the atomistic and CG pair correlation functions, the resulting pressure for the CG models is large compared with the pressure of the atomistic system. We find that correcting the potential to match the reference pressure leads to nonbonded interactions with much deeper minima and slightly smaller effective bead diameter. However, simulations with potentials generated by IBI and pressure-corrected IBI result in similar mean-square displacements (MSDs) and stress autocorrelation functions G( t) for PE melts. While the time rescaling factor required to match CG and atomistic models is the same for pressure- and non-pressure-corrected CG models, it strongly depends on temperature. Furthermore, transferability was investigated by comparing the MSDs and stress autocorrelation functions for potentials developed at different temperatures.« less

75 FR 39042 - Solicitation for a Cooperative Agreement: The Norval Morris Project Implementation Phase

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-07

... model designed to provide correctional agencies with a step-by-step approach to promote systemic change..., evidence-based approaches, evaluate their potential to inform correctional policy and practice, create... outside the corrections field to develop interdisciplinary approaches and draw on professional networks...

Monetary Incentives Improve Recall of Research Consent Information: A Randomized Pilot Study

PubMed Central

Festinger, David S.; Marlowe, Douglas B.; Croft, Jason R.; Dugosh, Karen L.; Arabia, Patricia L.; Benasutti, Kathleen M.

2011-01-01

Research participants often fail to recall substantial amounts of informed consent information after delays of only a few days. Numerous interventions have proven effective at improving consent recall; however, virtually all have focused on compensating for potential cognitive deficits and have ignored motivational factors. In this pilot study, we randomly assigned 31 drug court clients participating in a clinical research trial to a standard consent procedure or to the same procedure plus incentives for correctly recalling consent information. The incentive group was told they would receive $5 for each of the 15 consent items they could answer correctly 1-week later. At the follow-up, the incentive group recalled a significantly greater percentage of consent information overall than the standard group (65% vs. 42%; p < .01). Similar findings were observed for specific categories of consent information, including study purpose and design, risks and benefits, and human subject protections. Effect sizes were all large (d = 0.89 to 1.25). Findings suggest that motivation plays a key role in recall of consent information and should be considered in the development of future interventions. PMID:19331486

Study of CPM Device used for Rehabilitation and Effective Pain Management Following Knee Alloplasty

NASA Astrophysics Data System (ADS)

Trochimczuk, R.; Kuźmierowski, T.; Anchimiuk, P.

2017-02-01

This paper defines the design assumptions for the construction of an original demonstration of a CPM device, based on which a solid virtual model will be created in a CAD software environment. The overall dimensions and other input parameters for the design were determined for the entire patient population according to an anatomical atlas of human measures. The medical and physiotherapeutic community were also consulted with respect to the proposed engineering solutions. The virtual model of the CPM device that will be created will be used for computer simulations of changes in motion parameters as a function of time, accounting for loads and static states. The results obtained from computer simulation will be used to confirm the correctness of the design adopted assumptions and of the accepted structure of the CPM mechanism, and potentially to introduce necessary corrections. They will also provide a basis for the development of a control strategy for the laboratory prototype and for the selection of the strategy of the patient's rehabilitation in the future. This paper will be supplemented with identification of directions of further research.

Predicting Fog in the Nocturnal Boundary Layer

NASA Astrophysics Data System (ADS)

Izett, Jonathan; van de Wiel, Bas; Baas, Peter; van der Linden, Steven; van Hooft, Antoon; Bosveld, Fred

2017-04-01

Fog is a global phenomenon that presents a hazard to navigation and human safety, resulting in significant economic impacts for air and shipping industries as well as causing numerous road traffic accidents. Accurate prediction of fog events, however, remains elusive both in terms of timing and occurrence itself. Statistical methods based on set threshold criteria for key variables such as wind speed have been developed, but high rates of correct prediction of fog events still lead to similarly high "false alarms" when the conditions appear favourable, but no fog forms. Using data from the CESAR meteorological observatory in the Netherlands, we analyze specific cases and perform statistical analyses of event climatology, in order to identify the necessary conditions for correct prediction of fog. We also identify potential "missing ingredients" in current analysis that could help to reduce the number of false alarms. New variables considered include the indicators of boundary layer stability, as well as the presence of aerosols conducive to droplet formation. The poster presents initial findings of new research as well as plans for continued research.

Toward integrated image guided liver surgery

NASA Astrophysics Data System (ADS)

Jarnagin, W. R.; Simpson, Amber L.; Miga, M. I.

2017-03-01

While clinical neurosurgery has benefited from the advent of frameless image guidance for over three decades, the translation of image guided technologies to abdominal surgery, and more specifically liver resection, has been far more limited. Fundamentally, the workflow, complexity, and presentation have confounded development. With the first real efforts in translation beginning at the turn of the millennia, the work in developing novel augmented technologies to enhance screening, planning, and surgery has come to realization for the field. In this paper, we will review several examples from our own work that demonstrate the impact of image-guided procedure methods in eight clinical studies that speak to: (1) the accuracy in planning for liver resection, (2) enhanced surgical planning with portal vein embolization impact, (3) linking splenic volume changes to post-hepatectomy complications, (4) enhanced intraoperative localization in surgically occult lesions, (5) validation of deformation correction, and a (6) a novel blinded study focused at the value of deformation correction. All six of these studies were achieved in human systems and show the potential impact image guided methodologies could make on liver tissue resection procedures.

The relevance of error analysis in graphical symbols evaluation.

PubMed

Piamonte, D P

1999-01-01

In an increasing number of modern tools and devices, small graphical symbols appear simultaneously in sets as parts of the human-machine interfaces. The presence of each symbol can influence the other's recognizability and correct association to its intended referents. Thus, aside from correct associations, it is equally important to perform certain error analysis of the wrong answers, misses, confusions, and even lack of answers. This research aimed to show how such error analyses could be valuable in evaluating graphical symbols especially across potentially different user groups. The study tested 3 sets of icons representing 7 videophone functions. The methods involved parameters such as hits, confusions, missing values, and misses. The association tests showed similar hit rates of most symbols across the majority of the participant groups. However, exploring the error patterns helped detect differences in the graphical symbols' performances between participant groups, which otherwise seemed to have similar levels of recognition. These are very valuable not only in determining the symbols to be retained, replaced or re-designed, but also in formulating instructions and other aids in learning to use new products faster and more satisfactorily.

NAD(+)-dependent activation of Sirt1 corrects the phenotype in a mouse model of mitochondrial disease.

PubMed

Cerutti, Raffaele; Pirinen, Eija; Lamperti, Costanza; Marchet, Silvia; Sauve, Anthony A; Li, Wei; Leoni, Valerio; Schon, Eric A; Dantzer, Françoise; Auwerx, Johan; Viscomi, Carlo; Zeviani, Massimo

2014-06-03

Mitochondrial disorders are highly heterogeneous conditions characterized by defects of the mitochondrial respiratory chain. Pharmacological activation of mitochondrial biogenesis has been proposed as an effective means to correct the biochemical defects and ameliorate the clinical phenotype in these severely disabling, often fatal, disorders. Pathways related to mitochondrial biogenesis are targets of Sirtuin1, a NAD(+)-dependent protein deacetylase. As NAD(+) boosts the activity of Sirtuin1 and other sirtuins, intracellular levels of NAD(+) play a key role in the homeostatic control of mitochondrial function by the metabolic status of the cell. We show here that supplementation with nicotinamide riboside, a natural NAD(+) precursor, or reduction of NAD(+) consumption by inhibiting the poly(ADP-ribose) polymerases, leads to marked improvement of the respiratory chain defect and exercise intolerance of the Sco2 knockout/knockin mouse, a mitochondrial disease model characterized by impaired cytochrome c oxidase biogenesis. This strategy is potentially translatable into therapy of mitochondrial disorders in humans. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

[Fractures of the lower extremities in childhood : Part 2: lower leg and ankle fractures].

PubMed

Voth, M; Kremer, L; Marzi, I

2017-11-01

The treatment of pediatric patients in trauma surgery is a special situation in every aspect. For deciding on the correct treatment of fractures of the lower leg and ankle joint, various parameters, such as residual growth rate, skeletal age and height of the patient are decisive. The differences between fractures in children and adolescents are the open epiphyseal plate and the resulting residual growth. The bones of young children have a higher healing tendency and a greater potential for correction than in adolescents. Especially in the lower leg and the ankle joint, the potential for correction is decisive for the healing of fractures and for possible development of growth disorders. The limits of tolerance concerning axial malalignments and the expected spontaneous potential for correction must play an essential role for further treatment with conservative or operative therapy. This article deals with the special features of pediatric fractures of the lower leg and ankle joint.

76 FR 9051 - Notice of Inventory Completion: Washington State Department of Natural Resources, Olympia, WA and...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-16

... Anthropology, Seattle, WA; Correction AGENCY: National Park Service, Interior. ACTION: Notice; correction... of Washington, Department of Anthropology, Seattle, WA. The human remains were removed from... Notice, the University of Washington, Department of Anthropology, had believed it was in control of the...

75 FR 4567 - Agency Forms Undergoing Paperwork Reduction Act Review; Proposed Data Collections Submitted for...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-28

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention [30Day-10-0017... Comment and Recommendations; Correction AGENCY: Centers for Disease Control and Prevention. ACTION: Notice; correction. SUMMARY: The Centers for Disease Control and Prevention published a document in the Federal...

78 FR 70248 - Medical Gas Regulation Review; Announcement of Public Meeting; Correction

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-25

...: [email protected] ; or Christine Kirk, Center for Drug Evaluation and Research, Food and Drug... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Chapter I [Docket No...: Food and Drug Administration, HHS. ACTION: Notice of public meeting; correction. SUMMARY: The Food and...

21 CFR 99.401 - Corrective actions and cessation of dissemination of information.

Code of Federal Regulations, 2010 CFR

2010-04-01

... HEALTH AND HUMAN SERVICES GENERAL DISSEMINATION OF INFORMATION ON UNAPPROVED/NEW USES FOR MARKETED DRUGS... cessation of dissemination of information. (a) FDA actions based on post dissemination data. If FDA receives... requirements; or (2) Order the manufacturer to cease dissemination of information and to take corrective action...

42 CFR 93.521 - Correction of the transcript.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Correction of the transcript. 93.521 Section 93.521 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES HEALTH ASSESSMENTS AND HEALTH EFFECTS STUDIES OF HAZARDOUS SUBSTANCES RELEASES AND FACILITIES PUBLIC HEALTH SERVICE POLICIES ON...

Engineering Management for Zone Construction of Ships

DTIC Science & Technology

1985-09-01

Theory has steadily developed along with the better understanding of human relations, moti- vation and worklife sciences. That this is so, is clear from a...will not accomplish its goals effectively and efficiently if it is not staffed with the correct number of people with the correct balance of education

76 FR 35221 - Epidemiology Program for American Indian/Alaska Native Tribes and Urban Indian Communities...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-16

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Indian Health Service Epidemiology Program for American Indian/Alaska Native Tribes and Urban Indian Communities; Correction AGENCY: Indian Health Service, HHS. ACTION: Notice; correction. SUMMARY: The Indian Health Service published a document in the Federal...

42 CFR 493.1282 - Standard: Corrective actions.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 5 2010-10-01 2010-10-01 false Standard: Corrective actions. 493.1282 Section 493.1282 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES... values that are outside of the laboratory's reportable range of test results for the test system; and...

76 FR 16365 - Approval and Promulgation of Implementation Plans; Washington: Correction

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-23

... precursors to a NAAQS pollutant: Department of Ecology (Ecology): WAC 173-400-040 (except WAC 173- 400-040(1..., Ecology and SWCAA stated their support of EPA's approval of this correction and narrowing of the... address, as appropriate, disproportionate human health or environmental effects, using practicable and...

78 FR 63872 - Turtles Intrastate and Interstate Requirements

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-25

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 1240 [Docket No. FDA-2013-N-0639] Turtles Intrastate and Interstate Requirements Correction In rule document 2013-17751 appearing on pages 44878-44881 in the issue of July 25, 2013, make the following correction: On page 44879...

Rhythm as an affordance for the entrainment of movement.

PubMed

Cummins, Fred

2009-01-01

A general account of rhythm in human behaviour is provided, according to which rhythm inheres in the affordance that a signal provides for the entrainment of movement on the part of a perceiver. This generic account is supported by an explication of the central concepts of affordance and entrainment. When viewed in this light, rhythm appears as the correct explanandum to account for coordinated behaviour in a wide variety of situations, including such core senses as dance and the production of music. Speech may appear to be only marginally rhythmical under such an account, but several experimental studies reveal that speech, too, has the potential to entrain movement. (c) 2009 S. Karger AG, Basel.

Fournier's gangrene caused by Actinomyces funkei, Fusobacterium gonidiaformans and Clostridium hathewayi.

PubMed

Tena, Daniel; Losa, Cristina; Medina-Pascual, María José; Sáez-Nieto, Juan Antonio

2014-06-01

We report the first case of Fournier's gangrene caused by three unusual anaerobic organisms: Actinomyces funkei, Fusobacterium gonidiaformans and Clostridium hathewayi. The infection occurred in a 73-year-old man without typical risk factors for the development of Fournier's gangrene. Clinical outcome was good after prolonged antibiotic treatment and extensive debridement of the perineum. The case suggests that A. funkei, F. gonidiaformans and C. hathewayi should be considered as potential pathogens of Fournier's gangrene. Human infections caused by these organisms are very rare but can be underestimated because correct identification is very difficult, especially in polymicrobial infections such as Fournier's gangrene. Copyright © 2014 Elsevier Ltd. All rights reserved.

The science of stem cell biobanking: investing in the future.

PubMed

Diaferia, Giuseppe R; Cardano, Marina; Cattaneo, Monica; Spinelli, Chiara C; Dessì, Sara S; DeBlasio, Pasquale; Biunno, Ida

2012-01-01

The use of human stem cells in biomedical research projects is increasing steadily and the number of cells that are being derived develops at a remarkable pace. However, stem cells around the world are vastly different in their provenance, programming, and potentials. Furthermore, knowledge on the actual number of cell types, their derivation, availability, and characteristics is rather sparse. Usually, "colleague-supply" avenues constantly furnish cells to laboratories around the world without ensuring their correct identity, characterization, and quality. These parameters are critical if the cells will be eventually used in toxicology studies and drug discovery. Here, we outline some basic principles in establishing a stem cell-specific bank. Copyright © 2011 Wiley Periodicals, Inc.

NASA and Russian Space Agency sign agreement for additional Space Shuttle/Mir missions

PubMed

Huff, W

1994-01-01

On December 16, 1993 NASA Administrator Daniel S. Goldin [correction of Golden] and the Russian Space Agency (RSA) director Yuri Koptev signed a protocol agreeing to up to 10 Shuttle flights to Mir with a total of 24 months time aboard Mir for U.S. astronants, a program of scientific and technological research, and the upgrade and extension of the Mir lifetime during the period 1995-1997. This is the first of a three-phase program in human spaceflight cooperation which may culminate in the construction of an international Space Station. This agreement starts joint development of spacecraft environmental control and life support systems and potential common space suit.

Serum thymulin in human zinc deficiency.

PubMed Central

Prasad, A S; Meftah, S; Abdallah, J; Kaplan, J; Brewer, G J; Bach, J F; Dardenne, M

1988-01-01

The activity of thymulin (a thymic hormone) is dependent on the presence of zinc in the molecule. We assayed serum thymulin activity in three models of mildly zinc-deficient (ZD) human subjects before and after zinc supplementation: (a) two human volunteers in whom a specific and mild zinc deficiency was induced by dietary means; (b) six mildly ZD adult sickle cell anemia (SCA) subjects; and (c) six mildly ZD adult non-SCA subjects. Their plasma zinc levels were normal and they showed no overt clinical manifestations of zinc deficiency. The diagnosis of mild zinc deficiency was based on the assay of zinc in lymphocytes, granulocytes, and platelets. Serum thymulin activity was decreased as a result of mild zinc deficiency and was corrected by in vivo and in vitro zinc supplementation, suggesting that this parameter was a sensitive indicator of zinc deficiency in humans. An increase in T101-, sIg-cells, decrease in T4+/T8+ ratio, and decreased IL 2 activity were observed in the experimental human model during the zinc depletion phase, all of which were corrected after repletion with zinc. Similar changes in lymphocyte subpopulation, correctable with zinc supplementation, were also observed in mildly ZD SCA subjects. Inasmuch as thymulin is known to induce intra- and extrathymic T cell differentiation, our studies provide a possible mechanism for the role of zinc on T cell functions. Images PMID:3262625

Cytotoxicity evaluation using cryopreserved primary human hepatocytes in various culture formats.

PubMed

Richert, Lysiane; Baze, Audrey; Parmentier, Céline; Gerets, Helga H J; Sison-Young, Rowena; Dorau, Martina; Lovatt, Cerys; Czich, Andreas; Goldring, Christopher; Park, B Kevin; Juhila, Satu; Foster, Alison J; Williams, Dominic P

2016-09-06

Sixteen training compounds selected in the IMI MIP-DILI consortium, 12 drug-induced liver injury (DILI) positive compounds and 4 non-DILI compounds, were assessed in cryopreserved primary human hepatocytes. When a ten-fold safety margin threshold was applied, the non-DILI-compounds were correctly identified 2h following a single exposure to pooled human hepatocytes (n=13 donors) in suspension and 14-days following repeat dose exposure (3 treatments) to an established 3D-microtissue co-culture (3D-MT co-culture, n=1 donor) consisting of human hepatocytes co-cultured with non-parenchymal cells (NPC). In contrast, only 5/12 DILI-compounds were correctly identified 2h following a single exposure to pooled human hepatocytes in suspension. Exposure of the 2D-sandwich culture human hepatocyte monocultures (2D-sw) for 3days resulted in the correct identification of 11/12 DILI-positive compounds, whereas exposure of the human 3D-MT co-cultures for 14days resulted in identification of 9/12 DILI-compounds; in addition to ximelagatran (also not identified by 2D-sw monocultures, Sison-Young et al., 2016), the 3D-MT co-cultures failed to detect amiodarone and bosentan. The sensitivity of the 2D human hepatocytes co-cultured with NPC to ximelagatran was increased in the presence of lipopolysaccharide (LPS), but only at high concentrations, therefore preventing its classification as a DILI positive compound. In conclusion (1) despite suspension human hepatocytes having the greatest metabolic capacity in the short term, they are the least predictive of clinical DILI across the MIP-DILI test compounds, (2) longer exposure periods than 72h of human hepatocytes do not allow to increase DILI-prediction rate, (3) co-cultures of human hepatocytes with NPC, in the presence of LPS during the 72h exposure period allow the assessment of innate immune system involvement of a given drug. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Expression of 11beta-hydroxysteroid-dehydrogenase type 2 in human thymus.

PubMed

Almanzar, Giovanni; Mayerl, Christina; Seitz, Jan-Christoph; Höfner, Kerstin; Brunner, Andrea; Wild, Vanessa; Jahn, Daniel; Geier, Andreas; Fassnacht, Martin; Prelog, Martina

2016-06-01

11beta-hydroxysteroid-dehydrogenase type 2 (11β-HSD2) is a high affinity dehydrogenase which rapidly inactivates physiologically-active glucocorticoids to protect key tissues. 11β-HSD2 expression has been described in peripheral cells of the innate and the adaptive immune system as well as in murine thymus. In absence of knowledge of 11β-HSD2 expression in human thymus, the study aimed to localize 11β-HSD2 in human thymic tissue. Thymic tissue was taken of six healthy, non-immunologically impaired male infants below 12months of age with congenital heart defects who had to undergo correction surgery. 11β-HSD2 protein expression was analyzed by immunohistochemistry and Western blot. Kidney tissue, peripheral blood mononuclear cells (PBMCs) and human umbilical vein endothelial cells (HUVEC) were taken as positive controls. Significant expression of 11β-HSD2 protein was found at single cell level in thymus parenchyma, at perivascular sites of capillaries and small vessels penetrating the thymus lobuli and within Hassall's bodies. The present study demonstrates that 11β-HSD2 is expressed in human thymus with predominant perivascular expression and also within Hassall's bodies. To our knowledge, this is the first report confirming 11β-HSD2 expression at the protein level in human thymic tissue underlining a potential role of this enzyme in regulating glucocorticoid function at the thymic level. Copyright © 2016 Elsevier Inc. All rights reserved.

Identification of Suitable Areas for West Nile Virus Circulation in Tunisia.

PubMed

Ben Hassine, T; Conte, A; Calistri, P; Candeloro, L; Ippoliti, C; De Massis, F; Danzetta, M L; Bejaoui, M; Hammami, S

2017-04-01

West Nile virus (WNV) is a mosquito-transmitted Flavivirus belonging to the Japanese encephalitis antigenic complex of the Flaviviridae family. It is transmitted primarily by the bite of infected mosquitoes, particularly Culex spp. and Aedes/Ochlerotatus spp., which acquire the virus by feeding on viraemic birds. Humans, horses and other mammals are regarded as incidental or dead-end hosts. In the last decades, an increasing number of cases of WNV infection in horses and humans have been notified in the Mediterranean basin. In Tunisia, human cases of WNV-related meningoencephalitis were detected in 1997, 2003, 2007, 2010, 2011 and 2012. Based on the analysis of climatic and environmental conditions found in the locations where human cases have been reported in 2012, the aim of this study was to identify similar areas in Tunisia potentially at risk of disease occurrence. Data related to 85 neuroinvasive West Nile fever (WNF) human cases were georeferenced and a set of environmental and climatic variables (wetlands and humid areas, normalized difference vegetation index (NDVI), temperatures and elevation, migratory bird settlements) were used in the analysis. Areas, ecologically similar to those where human cases were detected, were identified using the Mahalanobis distance statistic. A leave-one-out cross-validation was performed to validate the sensitivity of the model, and 78 of 85 points were correctly classified. © 2015 Blackwell Verlag GmbH.

Use of Wild Bird Surveillance, Human Case Data and GIS Spatial Analysis for Predicting Spatial Distributions of West Nile Virus in Greece

PubMed Central

Valiakos, George; Papaspyropoulos, Konstantinos; Giannakopoulos, Alexios; Birtsas, Periklis; Tsiodras, Sotirios; Hutchings, Michael R.; Spyrou, Vassiliki; Pervanidou, Danai; Athanasiou, Labrini V.; Papadopoulos, Nikolaos; Tsokana, Constantina; Baka, Agoritsa; Manolakou, Katerina; Chatzopoulos, Dimitrios; Artois, Marc; Yon, Lisa; Hannant, Duncan; Petrovska, Liljana; Hadjichristodoulou, Christos; Billinis, Charalambos

2014-01-01

West Nile Virus (WNV) is the causative agent of a vector-borne, zoonotic disease with a worldwide distribution. Recent expansion and introduction of WNV into new areas, including southern Europe, has been associated with severe disease in humans and equids, and has increased concerns regarding the need to prevent and control future WNV outbreaks. Since 2010, 524 confirmed human cases of the disease have been reported in Greece with greater than 10% mortality. Infected mosquitoes, wild birds, equids, and chickens have been detected and associated with human disease. The aim of our study was to establish a monitoring system with wild birds and reported human cases data using Geographical Information System (GIS). Potential distribution of WNV was modelled by combining wild bird serological surveillance data with environmental factors (e.g. elevation, slope, land use, vegetation density, temperature, precipitation indices, and population density). Local factors including areas of low altitude and proximity to water were important predictors of appearance of both human and wild bird cases (Odds Ratio = 1,001 95%CI = 0,723–1,386). Using GIS analysis, the identified risk factors were applied across Greece identifying the northern part of Greece (Macedonia, Thrace) western Greece and a number of Greek islands as being at highest risk of future outbreaks. The results of the analysis were evaluated and confirmed using the 161 reported human cases of the 2012 outbreak predicting correctly (Odds = 130/31 = 4,194 95%CI = 2,841–6,189) and more areas were identified for potential dispersion in the following years. Our approach verified that WNV risk can be modelled in a fast cost-effective way indicating high risk areas where prevention measures should be implemented in order to reduce the disease incidence. PMID:24806216

Application of a new high-speed magnetic deformable mirror for in-vivo retinal imaging

NASA Astrophysics Data System (ADS)

Balderas-Mata, Sandra E.; Jones, Steven M.; Zawadzki, Robert J.; Werner, John S.

2011-08-01

Nowadays in ophthalmologic practice several commercial instruments are available to image patient retinas in vivo. Many modern fundus cameras and confocal scanning laser ophthalmoscopes allow acquisition of two dimensional en face images of the retina with both back reflected as well as fluorescent light. Additionally, optical coherence tomography systems allow non-invasive probing of three-dimensional retinal morphology. For all of these instruments the available lateral resolution is limited by optical quality of the human eye used as the imaging objective. To improve lateral resolution and achieve diffraction-limited imaging, adaptive optics (AO) can be implemented with any of these imaging systems to correct both static and dynamic aberrations inherent in human eyes. Most of the wavefront correctors used previously in AO systems have limited dynamic range and an insufficient number of actuators to achieve diffraction-limited correction of most human eyes. Thus, additional corrections were necessary, either by trial lenses or additional deformable mirrors (DMs). The UC Davis AO flood-illuminated fundus camera system described in this paper has been previously used to acquire in vivo images of the photoreceptor mosaic and for psychophysical studies on normal and diseased retinas. These results were acquired using a DM manufactured by Litton ITEK (DM109), which has 109 actuators arranged in a hexagonal array below a continuous front-surface mirror. It has an approximate surface actuator stroke of +/-2μm. Here we present results with a new hi-speed magnetic DM manufactured by ALPAO (DM97, voice coil technology), which has 97 actuators and similar inter-actuator stroke (>3μm, mirror surface) but much higher low-order aberration correction (defocus stroke of at least +/-30μm) than the previous one. In this paper we report results of testing performance of the ALPAO DM for the correction of human eye aberrations. Additionally changes made to our AO flood illuminated system are presented along with images of the model eye retina and in-vivo human retina acquired with this system.

Population of 224 realistic human subject-based computational breast phantoms

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

Erickson, David W.; Wells, Jered R., E-mail: jered.wells@duke.edu; Sturgeon, Gregory M.

Purpose: To create a database of highly realistic and anatomically variable 3D virtual breast phantoms based on dedicated breast computed tomography (bCT) data. Methods: A tissue classification and segmentation algorithm was used to create realistic and detailed 3D computational breast phantoms based on 230 + dedicated bCT datasets from normal human subjects. The breast volume was identified using a coarse three-class fuzzy C-means segmentation algorithm which accounted for and removed motion blur at the breast periphery. Noise in the bCT data was reduced through application of a postreconstruction 3D bilateral filter. A 3D adipose nonuniformity (bias field) correction was thenmore » applied followed by glandular segmentation using a 3D bias-corrected fuzzy C-means algorithm. Multiple tissue classes were defined including skin, adipose, and several fractional glandular densities. Following segmentation, a skin mask was produced which preserved the interdigitated skin, adipose, and glandular boundaries of the skin interior. Finally, surface modeling was used to produce digital phantoms with methods complementary to the XCAT suite of digital human phantoms. Results: After rejecting some datasets due to artifacts, 224 virtual breast phantoms were created which emulate the complex breast parenchyma of actual human subjects. The volume breast density (with skin) ranged from 5.5% to 66.3% with a mean value of 25.3% ± 13.2%. Breast volumes ranged from 25.0 to 2099.6 ml with a mean value of 716.3 ± 386.5 ml. Three breast phantoms were selected for imaging with digital compression (using finite element modeling) and simple ray-tracing, and the results show promise in their potential to produce realistic simulated mammograms. Conclusions: This work provides a new population of 224 breast phantoms based on in vivo bCT data for imaging research. Compared to previous studies based on only a few prototype cases, this dataset provides a rich source of new cases spanning a wide range of breast types, volumes, densities, and parenchymal patterns.« less

Population of 224 realistic human subject-based computational breast phantoms

PubMed Central

Erickson, David W.; Wells, Jered R.; Sturgeon, Gregory M.; Dobbins, James T.; Segars, W. Paul; Lo, Joseph Y.

2016-01-01

Purpose: To create a database of highly realistic and anatomically variable 3D virtual breast phantoms based on dedicated breast computed tomography (bCT) data. Methods: A tissue classification and segmentation algorithm was used to create realistic and detailed 3D computational breast phantoms based on 230 + dedicated bCT datasets from normal human subjects. The breast volume was identified using a coarse three-class fuzzy C-means segmentation algorithm which accounted for and removed motion blur at the breast periphery. Noise in the bCT data was reduced through application of a postreconstruction 3D bilateral filter. A 3D adipose nonuniformity (bias field) correction was then applied followed by glandular segmentation using a 3D bias-corrected fuzzy C-means algorithm. Multiple tissue classes were defined including skin, adipose, and several fractional glandular densities. Following segmentation, a skin mask was produced which preserved the interdigitated skin, adipose, and glandular boundaries of the skin interior. Finally, surface modeling was used to produce digital phantoms with methods complementary to the XCAT suite of digital human phantoms. Results: After rejecting some datasets due to artifacts, 224 virtual breast phantoms were created which emulate the complex breast parenchyma of actual human subjects. The volume breast density (with skin) ranged from 5.5% to 66.3% with a mean value of 25.3% ± 13.2%. Breast volumes ranged from 25.0 to 2099.6 ml with a mean value of 716.3 ± 386.5 ml. Three breast phantoms were selected for imaging with digital compression (using finite element modeling) and simple ray-tracing, and the results show promise in their potential to produce realistic simulated mammograms. Conclusions: This work provides a new population of 224 breast phantoms based on in vivo bCT data for imaging research. Compared to previous studies based on only a few prototype cases, this dataset provides a rich source of new cases spanning a wide range of breast types, volumes, densities, and parenchymal patterns. PMID:26745896

Intensity inhomogeneity correction for magnetic resonance imaging of human brain at 7T.

PubMed

Uwano, Ikuko; Kudo, Kohsuke; Yamashita, Fumio; Goodwin, Jonathan; Higuchi, Satomi; Ito, Kenji; Harada, Taisuke; Ogawa, Akira; Sasaki, Makoto

2014-02-01

To evaluate the performance and efficacy for intensity inhomogeneity correction of various sequences of the human brain in 7T MRI using the extended version of the unified segmentation algorithm. Ten healthy volunteers were scanned with four different sequences (2D spin echo [SE], 3D fast SE, 2D fast spoiled gradient echo, and 3D time-of-flight) by using a 7T MRI system. Intensity inhomogeneity correction was performed using the "New Segment" module in SPM8 with four different values (120, 90, 60, and 30 mm) of full width at half maximum (FWHM) in Gaussian smoothness. The uniformity in signals in the entire white matter was evaluated using the coefficient of variation (CV); mean signal intensities between the subcortical and deep white matter were compared, and contrast between subcortical white matter and gray matter was measured. The length of the lenticulostriate (LSA) was measured on maximum intensity projection (MIP) images in the original and corrected images. In all sequences, the CV decreased as the FWHM value decreased. The differences of mean signal intensities between subcortical and deep white matter also decreased with smaller FWHM values. The contrast between white and gray matter was maintained at all FWHM values. LSA length was significantly greater in corrected MIP than in the original MIP images. Intensity inhomogeneity in 7T MRI can be successfully corrected using SPM8 for various scan sequences.

Long-term correction of very long-chain acyl-coA dehydrogenase deficiency in mice using AAV9 gene therapy.

PubMed

Keeler, Allison M; Conlon, Thomas; Walter, Glenn; Zeng, Huadong; Shaffer, Scott A; Dungtao, Fu; Erger, Kirsten; Cossette, Travis; Tang, Qiushi; Mueller, Christian; Flotte, Terence R

2012-06-01

Very long-chain acyl-coA dehydrogenase (VLCAD) is the rate-limiting step in mitochondrial fatty acid oxidation. VLCAD-deficient mice and patients clinical symptoms stem from not only an energy deficiency but also long-chain metabolite accumulations. VLCAD-deficient mice were treated systemically with 1 × 10(12) vector genomes of recombinant adeno-associated virus 9 (rAAV9)-VLCAD. Biochemical correction was observed in vector-treated mice beginning 2 weeks postinjection, as characterized by a significant drop in long-chain fatty acyl accumulates in whole blood after an overnight fast. Changes persisted through the termination point around 20 weeks postinjection. Magnetic resonance spectroscopy (MRS) and tandem mass spectrometry (MS/MS) revealed normalization of intramuscular lipids in treated animals. Correction was not observed in liver tissue extracts, but cardiac muscle extracts showed significant reduction of long-chain metabolites. Disease-specific phenotypes were characterized, including thermoregulation and maintenance of euglycemia after a fasting cold challenge. Internal body temperatures of untreated VLCAD(-/-) mice dropped below 20 °C and the mice became lethargic, requiring euthanasia. In contrast, all rAAV9-treated VLCAD(-/-) mice and the wild-type controls maintained body temperatures. rAAV9-treated VLCAD(-/-) mice maintained euglycemia, whereas untreated VLCAD(-/-) mice suffered hypoglycemia following a fasting cold challenge. These promising results suggest rAAV9 gene therapy as a potential treatment for VLCAD deficiency in humans.

Phase-aberration correction with a 3-D ultrasound scanner: feasibility study.

PubMed

Ivancevich, Nikolas M; Dahl, Jeremy J; Trahey, Gregg E; Smith, Stephen W

2006-08-01

We tested the feasibility of using adaptive imaging, namely phase-aberration correction, with two-dimensional (2-D) arrays and real-time, 3-D ultrasound. Because of the high spatial frequency content of aberrators, 2-D arrays, which generally have smaller pitch and thus higher spatial sampling frequency, and 3-D imaging show potential to improve the performance of adaptive imaging. Phase-correction algorithms improve image quality by compensating for tissue-induced errors in beamforming. Using the illustrative example of transcranial ultrasound, we have evaluated our ability to perform adaptive imaging with a real-time, 3-D scanner. We have used a polymer casting of a human temporal bone, root-mean-square (RMS) phase variation of 45.0 ns, full-width-half-maximum (FWHM) correlation length of 3.35 mm, and an electronic aberrator, 100 ns RMS, 3.76 mm correlation, with tissue phantoms as illustrative examples of near-field, phase-screen aberrators. Using the multilag, least-squares, cross-correlation method, we have shown the ability of 3-D adaptive imaging to increase anechoic cyst identification, image brightness, contrast-to-speckle ratio (CSR), and, in 3-D color Doppler experiments, the ability to visualize flow. For a physical aberrator skull casting we saw CSR increase by 13% from 1.01 to 1.14, while the number of detectable cysts increased from 4.3 to 7.7.

CRISPR-mediated genotypic and phenotypic correction of a chronic granulomatous disease mutation in human iPS cells

PubMed Central

Flynn, Rowan; Grundmann, Alexander; Renz, Peter; Hänseler, Walther; James, William S.; Cowley, Sally A.; Moore, Michael D.

2015-01-01

Chronic granulomatous disease (CGD) is a rare genetic disease characterized by severe and persistent childhood infections. It is caused by the lack of an antipathogen oxidative burst, normally performed by phagocytic cells to contain and clear bacterial and fungal growth. Restoration of immune function can be achieved with heterologous bone marrow transplantation; however, autologous bone marrow transplantation would be a preferable option. Thus, a method is required to recapitulate the function of the diseased gene within the patient's own cells. Gene therapy approaches for CGD have employed randomly integrating viruses with concomitant issues of insertional mutagenesis, inaccurate gene dosage, and gene silencing. Here, we explore the potential of the recently described clustered regularly interspaced short palindromic repeat (CRISPR)-Cas9 site-specific nuclease system to encourage repair of the endogenous gene by enhancing the levels of homologous recombination. Using induced pluripotent stem cells derived from a CGD patient containing a single intronic mutation in the CYBB gene, we show that footprintless gene editing is a viable option to correct disease mutations. Gene correction results in restoration of oxidative burst function in iPS-derived phagocytes by reintroduction of a previously skipped exon in the cytochrome b-245 heavy chain (CYBB) protein. This study provides proof-of-principle for a gene therapy approach to CGD treatment using CRISPR-Cas9. PMID:26101162

Corrective Action Investigation Plan for Corrective Action Unit 576: Miscellaneous Radiological Sites and Debris Nevada National Security Site, Nevada, Revision 0

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

Matthews, Patrick

Corrective Action Unit (CAU) 576 is located in Areas 2, 3, 5, 8, and 9 of the Nevada National Security Site, which is approximately 65 miles northwest of Las Vegas, Nevada. CAU 576 is a grouping of sites where there has been a suspected release of contamination associated with nuclear testing. This document describes the planned investigation of CAU 576, which comprises the following corrective action sites (CASs): 00-99-01, Potential Source Material; 02-99-12, U-2af (Kennebec) Surface Rad-Chem Piping; 03-99-20, Area 3 Subsurface Rad-Chem Piping; 05-19-04, Frenchman Flat Rad Waste Dump ; 09-99-08, U-9x (Allegheny) Subsurface Rad-Chem Piping; 09-99-09, U-9its u24more » (Avens-Alkermes) Surface Contaminated Flex Line These sites are being investigated because existing information on the nature and extent of potential contamination is insufficient to evaluate and recommend corrective action alternatives (CAAs). Additional information will be obtained by conducting a corrective action investigation before evaluating CAAs and selecting the appropriate corrective action for each CAS. The results of the field investigation will support a defensible evaluation of viable CAAs that will be presented in the Corrective Action Decision Document (CADD).« less

How humans use visual optic flow to regulate stepping during walking.

PubMed

Salinas, Mandy M; Wilken, Jason M; Dingwell, Jonathan B

2017-09-01

Humans use visual optic flow to regulate average walking speed. Among many possible strategies available, healthy humans walking on motorized treadmills allow fluctuations in stride length (L n ) and stride time (T n ) to persist across multiple consecutive strides, but rapidly correct deviations in stride speed (S n =L n /T n ) at each successive stride, n. Several experiments verified this stepping strategy when participants walked with no optic flow. This study determined how removing or systematically altering optic flow influenced peoples' stride-to-stride stepping control strategies. Participants walked on a treadmill with a virtual reality (VR) scene projected onto a 3m tall, 180° semi-cylindrical screen in front of the treadmill. Five conditions were tested: blank screen ("BLANK"), static scene ("STATIC"), or moving scene with optic flow speed slower than ("SLOW"), matched to ("MATCH"), or faster than ("FAST") walking speed. Participants took shorter and faster strides and demonstrated increased stepping variability during the BLANK condition compared to the other conditions. Thus, when visual information was removed, individuals appeared to walk more cautiously. Optic flow influenced both how quickly humans corrected stride speed deviations and how successful they were at enacting this strategy to try to maintain approximately constant speed at each stride. These results were consistent with Weber's law: healthy adults more-rapidly corrected stride speed deviations in a no optic flow condition (the lower intensity stimuli) compared to contexts with non-zero optic flow. These results demonstrate how the temporal characteristics of optic flow influence ability to correct speed fluctuations during walking. Copyright © 2017 Elsevier B.V. All rights reserved.

Wigner expansions for partition functions of nonrelativistic and relativistic oscillator systems

NASA Technical Reports Server (NTRS)

Zylka, Christian; Vojta, Guenter

1993-01-01

The equilibrium quantum statistics of various anharmonic oscillator systems including relativistic systems is considered within the Wigner phase space formalism. For this purpose the Wigner series expansion for the partition function is generalized to include relativistic corrections. The new series for partition functions and all thermodynamic potentials yield quantum corrections in terms of powers of h(sup 2) and relativistic corrections given by Kelvin functions (modified Hankel functions) K(sub nu)(mc(sup 2)/kT). As applications, the symmetric Toda oscillator, isotonic and singular anharmonic oscillators, and hindered rotators, i.e. oscillators with cosine potential, are addressed.

40 CFR 146.7 - Corrective action.

Code of Federal Regulations, 2014 CFR

2014-07-01

... INJECTION CONTROL PROGRAM: CRITERIA AND STANDARDS General Provisions § 146.7 Corrective action. In...; (b) Nature of native fluids or by-products of injection; (c) Potentially affected population; (d...

Visual Culture, Art History and the Humanities

ERIC Educational Resources Information Center

Castaneda, Ivan

2009-01-01

This essay will discuss the need for the humanities to address visual culture studies as part of its interdisciplinary mission in today's university. Although mostly unnoticed in recent debates in the humanities over historical and theoretical frameworks, the relatively new field of visual culture has emerged as a corrective to a growing…

40 CFR 264.15 - General inspection requirements.

Code of Federal Regulations, 2011 CFR

2011-07-01

... human health. The owner or operator must conduct these inspections often enough to identify problems in time to correct them before they harm human health or the environment. (b)(1) The owner or operator... important to preventing, detecting, or responding to environmental or human health hazards. (2) He must keep...

40 CFR 264.15 - General inspection requirements.

Code of Federal Regulations, 2013 CFR

2013-07-01

... human health. The owner or operator must conduct these inspections often enough to identify problems in time to correct them before they harm human health or the environment. (b)(1) The owner or operator... important to preventing, detecting, or responding to environmental or human health hazards. (2) He must keep...

40 CFR 264.15 - General inspection requirements.

Code of Federal Regulations, 2012 CFR

2012-07-01

... human health. The owner or operator must conduct these inspections often enough to identify problems in time to correct them before they harm human health or the environment. (b)(1) The owner or operator... important to preventing, detecting, or responding to environmental or human health hazards. (2) He must keep...

40 CFR 264.15 - General inspection requirements.

Code of Federal Regulations, 2014 CFR

2014-07-01

... human health. The owner or operator must conduct these inspections often enough to identify problems in time to correct them before they harm human health or the environment. (b)(1) The owner or operator... important to preventing, detecting, or responding to environmental or human health hazards. (2) He must keep...

Correctors and Potentiators Rescue Function of the Truncated W1282X-Cystic Fibrosis Transmembrane Regulator (CFTR) Translation Product.

PubMed

Haggie, Peter M; Phuan, Puay-Wah; Tan, Joseph-Anthony; Xu, Haijin; Avramescu, Radu G; Perdomo, Doranda; Zlock, Lorna; Nielson, Dennis W; Finkbeiner, Walter E; Lukacs, Gergely L; Verkman, Alan S

2017-01-20

W1282X is the fifth most common cystic fibrosis transmembrane regulator (CFTR) mutation that causes cystic fibrosis. Here, we investigated the utility of a small molecule corrector/potentiator strategy, as used for ΔF508-CFTR, to produce functional rescue of the truncated translation product of the W1282X mutation, CFTR 1281 , without the need for read-through. In transfected cell systems, certain potentiators and correctors, including VX-809 and VX-770, increased CFTR 1281 activity. To identify novel correctors and potentiators with potentially greater efficacy on CFTR 1281 , functional screens were done of ∼30,000 synthetic small molecules and drugs/nutraceuticals in CFTR 1281 -transfected cells. Corrector scaffolds of 1-arylpyrazole-4-arylsulfonyl-piperazine and spiro-piperidine-quinazolinone classes were identified with up to ∼5-fold greater efficacy than VX-809, some of which were selective for CFTR 1281 , whereas others also corrected ΔF508-CFTR. Several novel potentiator scaffolds were identified with efficacy comparable with VX-770; remarkably, a phenylsulfonamide-pyrrolopyridine acted synergistically with VX-770 to increase CFTR 1281 function ∼8-fold over that of VX-770 alone, normalizing CFTR 1281 channel activity to that of wild type CFTR. Corrector and potentiator combinations were tested in primary cultures and conditionally reprogrammed cells generated from nasal brushings from one W1282X homozygous subject. Although robust chloride conductance was seen with correctors and potentiators in homozygous ΔF508 cells, increased chloride conductance was not found in W1282X cells despite the presence of adequate transcript levels. Notwithstanding the negative data in W1282X cells from one human subject, we speculate that corrector and potentiator combinations may have therapeutic efficacy in cystic fibrosis caused by the W1282X mutation, although additional studies are needed on human cells from W1282X subjects. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Correctors and Potentiators Rescue Function of the Truncated W1282X-Cystic Fibrosis Transmembrane Regulator (CFTR) Translation Product*♦

PubMed Central

Haggie, Peter M.; Phuan, Puay-Wah; Tan, Joseph-Anthony; Xu, Haijin; Avramescu, Radu G.; Perdomo, Doranda; Zlock, Lorna; Nielson, Dennis W.; Finkbeiner, Walter E.; Lukacs, Gergely L.; Verkman, Alan S.

2017-01-01

W1282X is the fifth most common cystic fibrosis transmembrane regulator (CFTR) mutation that causes cystic fibrosis. Here, we investigated the utility of a small molecule corrector/potentiator strategy, as used for ΔF508-CFTR, to produce functional rescue of the truncated translation product of the W1282X mutation, CFTR1281, without the need for read-through. In transfected cell systems, certain potentiators and correctors, including VX-809 and VX-770, increased CFTR1281 activity. To identify novel correctors and potentiators with potentially greater efficacy on CFTR1281, functional screens were done of ∼30,000 synthetic small molecules and drugs/nutraceuticals in CFTR1281-transfected cells. Corrector scaffolds of 1-arylpyrazole-4-arylsulfonyl-piperazine and spiro-piperidine-quinazolinone classes were identified with up to ∼5-fold greater efficacy than VX-809, some of which were selective for CFTR1281, whereas others also corrected ΔF508-CFTR. Several novel potentiator scaffolds were identified with efficacy comparable with VX-770; remarkably, a phenylsulfonamide-pyrrolopyridine acted synergistically with VX-770 to increase CFTR1281 function ∼8-fold over that of VX-770 alone, normalizing CFTR1281 channel activity to that of wild type CFTR. Corrector and potentiator combinations were tested in primary cultures and conditionally reprogrammed cells generated from nasal brushings from one W1282X homozygous subject. Although robust chloride conductance was seen with correctors and potentiators in homozygous ΔF508 cells, increased chloride conductance was not found in W1282X cells despite the presence of adequate transcript levels. Notwithstanding the negative data in W1282X cells from one human subject, we speculate that corrector and potentiator combinations may have therapeutic efficacy in cystic fibrosis caused by the W1282X mutation, although additional studies are needed on human cells from W1282X subjects. PMID:27895116

Effect of the corrected ionization potential and spatial distribution on the angular and energy distribution in tunnel ionization

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

Petrović, V. M.; Miladinović, T. B., E-mail: tanja.miladinovic@gmail.com

2016-05-15

Within the framework of the Ammosov–Delone–Krainov theory, we consider the angular and energy distribution of outgoing electrons due to ionization by a circularly polarized electromagnetic field. A correction of the ground ionization potential by the ponderomotive and Stark shift is incorporated in both distributions. Spatial dependence is analyzed.

The Detection and Correction of Bias in Student Ratings of Instruction.

ERIC Educational Resources Information Center

Haladyna, Thomas; Hess, Robert K.

1994-01-01

A Rasch model was used to detect and correct bias in Likert rating scales used to assess student perceptions of college teaching, using a database of ratings. Statistical corrections were significant, supporting the model's potential utility. Recommendations are made for a theoretical rationale and further research on the model. (Author/MSE)

A Three-Stage Model for Implementing Focused Written Corrective Feedback

ERIC Educational Resources Information Center

Chong, Sin Wang

2017-01-01

This article aims to show how the findings from written corrective feedback (WCF) research can be applied in practice. One particular kind of WCF--focused WCF--is brought into the spotlight. The article first summarizes major findings from focused WCF research to reveal the potential advantages of correcting a few preselected language items…

Human eyes do not need monochromatic aberrations for dynamic accommodation.

PubMed

Bernal-Molina, Paula; Marín-Franch, Iván; Del Águila-Carrasco, Antonio J; Esteve-Taboada, Jose J; López-Gil, Norberto; Kruger, Philip B; Montés-Micó, Robert

2017-09-01

To determine if human accommodation uses the eye's own monochromatic aberrations to track dynamic accommodative stimuli. Wavefront aberrations were measured while subjects monocularly viewed a monochromatic Maltese cross moving sinusoidally around 2D of accommodative demand with 1D amplitude at 0.2 Hz. The amplitude and phase (delay) of the accommodation response were compared to the actual vergence of the stimulus to obtain gain and temporal phase, calculated from wavefront aberrations recorded over time during experimental trials. The tested conditions were as follows: Correction of all the subject's aberrations except defocus (C); Correction of all the subject's aberrations except defocus and habitual second-order astigmatism (AS); Correction of all the subject's aberrations except defocus and odd higher-order aberrations (HOAs); Correction of all the subject's aberrations except defocus and even HOAs (E); Natural aberrations of the subject's eye, i.e., the adaptive-optics system only corrected the optical system's aberrations (N); Correction of all the subject's aberrations except defocus and fourth-order spherical aberration (SA). The correction was performed at 20 Hz and each condition was repeated six times in randomised order. Average gain (±2 standard errors of the mean) varied little across conditions; between 0.55 ± 0.06 (SA), and 0.62 ± 0.06 (AS). Average phase (±2 standard errors of the mean) also varied little; between 0.41 ± 0.02 s (E), and 0.47 ± 0.02 s (O). After Bonferroni correction, no statistically significant differences in gain or phase were found in the presence of specific monochromatic aberrations or in their absence. These results show that the eye's monochromatic aberrations are not necessary for accommodation to track dynamic accommodative stimuli. © 2017 The Authors. Ophthalmic and Physiological Optics published by John Wiley & Sons Ltd on behalf of College of Optometrists.

Comparison of FLAASH and QUAC atmospheric correction methods for Resourcesat-2 LISS-IV data

NASA Astrophysics Data System (ADS)

Saini, V.; Tiwari, R. K.; Gupta, R. P.

2016-05-01

The LISS-IV sensor aboard Resourcesat-2 is a modern relatively high resolution multispectral sensor having immense potential for generation of good quality land use land cover maps. It generates data in high (10-bit) radiometric resolution and 5.8 m spatial resolution and has three bands in the visible-near infrared region. This is of particular importance to global community as the data are provided at highly competitive prices. However, no literature describing the atmospheric correction of Resourcesat-2-LISS-IV data could be found. Further, without atmospheric correction full radiometric potential of any remote sensing data remains underutilized. The FLAASH and QUAC module of ENVI software are highly used by researchers for atmospheric correction of popular remote sensing data such as Landsat, SPOT, IKONOS, LISS-I, III etc. This article outlines a methodology for atmospheric correction of Resourcesat-2-LISS-IV data. Also, a comparison of reflectance from different atmospheric correction modules (FLAASH and QUAC) with TOA and standard data has been made to determine the best suitable method for reflectance estimation for this sensor.

Mesothelioma mortality in Europe: impact of asbestos consumption and simian virus 40

PubMed Central

Leithner, Katharina; Leithner, Andreas; Clar, Heimo; Weinhaeusel, Andreas; Radl, Roman; Krippl, Peter; Rehak, Peter; Windhager, Reinhard; Haas, Oskar A; Olschewski, Horst

2006-01-01

Background It is well established that asbestos is the most important cause of mesothelioma. The role of simian virus 40 (SV40) in mesothelioma development, on the other hand, remains controversial. This potential human oncogene has been introduced into various populations through contaminated polio vaccines. The aim of this study was to investigate whether the possible presence of SV40 in various European countries, as indicated either by molecular genetic evidence or previous exposure to SV40-contaminated vaccines, had any effect on pleural cancer rates in the respective countries. Methods We conducted a Medline search that covered the period from January 1969 to August 2005 for reports on the detection of SV40 DNA in human tissue samples. In addition, we collected all available information about the types of polio vaccines that had been used in these European countries and their SV40 contamination status. Results Our ecological analysis confirms that pleural cancer mortality in males, but not in females, correlates with the extent of asbestos exposure 25 – 30 years earlier. In contrast, neither the presence of SV40 DNA in tumor samples nor a previous vaccination exposure had any detectable influence on the cancer mortality rate in neither in males (asbestos-corrected rates) nor in females. Conclusion Using the currently existing data on SV40 prevalence, no association between SV40 prevalence and asbestos-corrected male pleural cancer can be demonstrated. PMID:17090323

Simultaneous SLO/OCT imaging of the human retina with axial eye motion correction.

PubMed

Pircher, Michael; Baumann, Bernhard; Götzinger, Erich; Sattmann, Harald; Hitzenberger, Christoph K

2007-12-10

It has been shown that transversal scanning (or en-face) optical coherence tomography (TS-OCT) represents an imaging modality capable to record high isotropic resolution images of the human retina in vivo. However, axial eye motion still remains a challenging problem of this technique. In this paper we introduce a novel method to compensate for this eye motion. An auxiliary spectral domain partial coherence interferometer (SD-PCI) was integrated into an existing TS-OCT system and used to measure accurately the position of the cornea. A light source emitting at 1310nm was used in the additional interferometer which enabled a nearly loss free coupling of the two measurement beams via a dichroic mirror. The recorded corneal position was used to drive an additional voice coil translation stage in the reference arm of the TS-OCT system to correct for axial eye motion. Currently, the correction can be performed with an update rate of ~200Hz. The TS-OCT instrument is operated with a line scan rate of 4000 transversal lines per second which enables simultaneous SLO/OCT imaging at a frame rate of 40fps. 3D data of the human retina with isotropic high resolution, that was sufficient to visualize the human cone mosaic in vivo, is presented.

Quantum Electrodynamical Shifts in Multivalent Heavy Ions.

PubMed

Tupitsyn, I I; Kozlov, M G; Safronova, M S; Shabaev, V M; Dzuba, V A

2016-12-16

The quantum electrodynamics (QED) corrections are directly incorporated into the most accurate treatment of the correlation corrections for ions with complex electronic structure of interest to metrology and tests of fundamental physics. We compared the performance of four different QED potentials for various systems to access the accuracy of QED calculations and to make a prediction of highly charged ion properties urgently needed for planning future experiments. We find that all four potentials give consistent and reliable results for ions of interest. For the strongly bound electrons, the nonlocal potentials are more accurate than the local potential.

Glucose-6-phosphate transporter gene therapy corrects metabolic and myeloid abnormalities in glycogen storage disease type Ib mice

PubMed Central

Yiu, Wai Han; Pan, Chi-Jiunn; Allamarvdasht, Mohammad; Kim, So Youn; Chou, Janice Y.

2008-01-01

Glycogen storage disease type Ib (GSD-Ib) is caused by a deficiency in the glucose-6-phosphate transporter (G6PT), an endoplasmic reticulum-associated transmembrane protein that is ubiquitously expressed. GSD-Ib patients suffer from disturbed glucose homeostasis and myeloid dysfunctions. To evaluate the feasibility of gene replacement therapy for GSD-Ib, we have infused adenoviral (Ad) vector containing human G6PT (Ad-hG6PT) into G6PT-deficient (G6PT-/-) mice that manifest symptoms characteristics of the human disorder. Ad-hG6PT-infusion restores significant levels of G6PT mRNA expression in the liver, bone marrow, and spleen and corrects metabolic as well as myeloid abnormalities in G6PT-/- mice. The G6PT-/- mice receiving gene therapy exhibit improved growth; normalized serum profiles for glucose, cholesterol, triglyceride, uric acid, and lactic acid; and reduced hepatic glycogen deposition. The therapy also corrects neutropenia and lowers the elevated serum levels of granulocyte colony stimulating factor. The development of bone and spleen in the infused G6PT-/- mice is improved and accompanied by increased cellularity and normalized myeloid progenitor cell frequencies in both tissues. This effective use of gene therapy to correct metabolic imbalances and myeloid dysfunctions in GSD-Ib mice holds promise for the future of gene therapy in humans. PMID:17006547

Higher-order corrections to the effective potential close to the jamming transition in the perceptron model

NASA Astrophysics Data System (ADS)

Altieri, Ada

2018-01-01

In view of the results achieved in a previously related work [A. Altieri, S. Franz, and G. Parisi, J. Stat. Mech. (2016) 093301], 10.1088/1742-5468/2016/09/093301, regarding a Plefka-like expansion of the free energy up to the second order in the perceptron model, we improve the computation here focusing on the role of third-order corrections. The perceptron model is a simple example of constraint satisfaction problem, falling in the same universality class as hard spheres near jamming and hence allowing us to get exact results in high dimensions for more complex settings. Our method enables to define an effective potential (or Thouless-Anderson-Palmer free energy), namely a coarse-grained functional, which depends on the generalized forces and the effective gaps between particles. The analysis of the third-order corrections to the effective potential reveals that, albeit irrelevant in a mean-field framework in the thermodynamic limit, they might instead play a fundamental role in considering finite-size effects. We also study the typical behavior of generalized forces and we show that two kinds of corrections can occur. The first contribution arises since the system is analyzed at a finite distance from jamming, while the second one is due to finite-size corrections. We nevertheless show that third-order corrections in the perturbative expansion vanish in the jamming limit both for the potential and the generalized forces, in agreement with the isostaticity argument proposed by Wyart and coworkers. Finally, we analyze the relevant scaling solutions emerging close to the jamming line, which define a crossover regime connecting the control parameters of the model to an effective temperature.

Higher-order corrections to the effective potential close to the jamming transition in the perceptron model.

PubMed

Altieri, Ada

2018-01-01

In view of the results achieved in a previously related work [A. Altieri, S. Franz, and G. Parisi, J. Stat. Mech. (2016) 093301]10.1088/1742-5468/2016/09/093301, regarding a Plefka-like expansion of the free energy up to the second order in the perceptron model, we improve the computation here focusing on the role of third-order corrections. The perceptron model is a simple example of constraint satisfaction problem, falling in the same universality class as hard spheres near jamming and hence allowing us to get exact results in high dimensions for more complex settings. Our method enables to define an effective potential (or Thouless-Anderson-Palmer free energy), namely a coarse-grained functional, which depends on the generalized forces and the effective gaps between particles. The analysis of the third-order corrections to the effective potential reveals that, albeit irrelevant in a mean-field framework in the thermodynamic limit, they might instead play a fundamental role in considering finite-size effects. We also study the typical behavior of generalized forces and we show that two kinds of corrections can occur. The first contribution arises since the system is analyzed at a finite distance from jamming, while the second one is due to finite-size corrections. We nevertheless show that third-order corrections in the perturbative expansion vanish in the jamming limit both for the potential and the generalized forces, in agreement with the isostaticity argument proposed by Wyart and coworkers. Finally, we analyze the relevant scaling solutions emerging close to the jamming line, which define a crossover regime connecting the control parameters of the model to an effective temperature.

The Deformity Angular Ratio: Does It Correlate With High-Risk Cases for Potential Spinal Cord Monitoring Alerts in Pediatric 3-Column Thoracic Spinal Deformity Corrective Surgery?

PubMed

Lewis, Noah D H; Keshen, Sam G N; Lenke, Lawrence G; Zywiel, Michael G; Skaggs, David L; Dear, Taylor E; Strantzas, Samuel; Lewis, Stephen J

2015-08-01

A retrospective analysis. The purpose of this study was to determine whether the deformity angular ratio (DAR) can reliably assess the neurological risks of patients undergoing deformity correction. Identifying high-risk patients and procedures can help ensure that appropriate measures are taken to minimize neurological complications during spinal deformity corrections. Subjectively, surgeons look at radiographs and evaluate the riskiness of the procedure. However, 2 curves of similar magnitude and location can have significantly different risks of neurological deficit during surgery. Whether the curve spans many levels or just a few can significantly influence surgical strategies. Lenke et al have proposed the DAR, which is a measure of curve magnitude per level of deformity. The data from 35 pediatric spinal deformity correction procedures with thoracic 3-column osteotomies were reviewed. Measurements from preoperative radiographs were used to calculate the DAR. Binary logistic regression was used to model the relationship between DARs (independent variables) and presence or absence of an intraoperative alert (dependent variable). In patients undergoing 3-column osteotomies, sagittal curve magnitude and total curve magnitude were associated with increased incidence of transcranial motor evoked potential changes. Total DAR greater than 45° per level and sagittal DAR greater than 22° per level were associated with a 75% incidence of a motor evoked potential alert, with the incidence increasing to 90% with sagittal DAR of 28° per level. In patients undergoing 3-column osteotomies for severe spinal deformities, the DAR was predictive of patients developing intraoperative motor evoked potential alerts. Identifying accurate radiographical, patient, and procedural risk factors in the correction of severe deformities can help prepare the surgical team to improve safety and outcomes when carrying out complex spinal corrections. 3.

Post-human body and beauty.

PubMed

Russo, Maria Teresa; Di Stefano, Nicola

2014-01-01

The article calls into question the very possibility of a post-human aesthetics, starting from the following premise: rather than post-human, it is more correct to speak of post-natural, indicating by this expression a reality produced through a new type of evolution, which does not simply change human nature, but de-natures it, radically transforming it into an artefact. This post-nature which aspires to be perfect, immortal, invulnerable, is entirely devoid of beauty. In fact, while there may be an aesthetic of the artificial and of the artefact if it is in relation to objects, there is, however, no aesthetic of the post-human body. This is because is configured as a non-body and does not have the characteristics for what is commonly intended as beauty (harmony between matter and form, a reflection of inner life, uniqueness). Also in this case, it is more correct to speak of post-beauty, which in its properties appears to be the mirror image of beauty and ultimately, represents its complete dissolution.

Multiconjugate adaptive optics applied to an anatomically accurate human eye model.

PubMed

Bedggood, P A; Ashman, R; Smith, G; Metha, A B

2006-09-04

Aberrations of both astronomical telescopes and the human eye can be successfully corrected with conventional adaptive optics. This produces diffraction-limited imagery over a limited field of view called the isoplanatic patch. A new technique, known as multiconjugate adaptive optics, has been developed recently in astronomy to increase the size of this patch. The key is to model atmospheric turbulence as several flat, discrete layers. A human eye, however, has several curved, aspheric surfaces and a gradient index lens, complicating the task of correcting aberrations over a wide field of view. Here we utilize a computer model to determine the degree to which this technology may be applied to generate high resolution, wide-field retinal images, and discuss the considerations necessary for optimal use with the eye. The Liou and Brennan schematic eye simulates the aspheric surfaces and gradient index lens of real human eyes. We show that the size of the isoplanatic patch of the human eye is significantly increased through multiconjugate adaptive optics.

Statistical Hypothesis Testing using CNN Features for Synthesis of Adversarial Counterexamples to Human and Object Detection Vision Systems

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

Raj, Sunny; Jha, Sumit Kumar; Pullum, Laura L.

Validating the correctness of human detection vision systems is crucial for safety applications such as pedestrian collision avoidance in autonomous vehicles. The enormous space of possible inputs to such an intelligent system makes it difficult to design test cases for such systems. In this report, we present our tool MAYA that uses an error model derived from a convolutional neural network (CNN) to explore the space of images similar to a given input image, and then tests the correctness of a given human or object detection system on such perturbed images. We demonstrate the capability of our tool on themore » pre-trained Histogram-of-Oriented-Gradients (HOG) human detection algorithm implemented in the popular OpenCV toolset and the Caffe object detection system pre-trained on the ImageNet benchmark. Our tool may serve as a testing resource for the designers of intelligent human and object detection systems.« less

Correction of xeroderma pigmentosum complementation group D mutant cell phenotypes by chromosome and gene transfer: Involvement of the human ERCC2 DNA repair gene

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

Flejter, W.L.; McDaniel, L.D.; Johns, D.

1992-01-01

Cultured cells from individuals afflicted with the genetically heterogeneous autosomal recessive disorder xeroderma pigmentosum (XP) exhibit sensitivity to UV radiation and defective nucleotide excision repair. Complementation of these mutant phenotypes after the introduction of single human chromosomes from repair-proficient cells into XP cells has provided a means of mapping the genes involved in this disease. The authors now report the phenotypic correction of XP cells from genetic complementation group D (XP-D) by a single human chromosome designated Tneo. Detailed molecular characterization of Tneo revealed a rearranged structure involving human chromosomes 16 and 19, including the excision repair cross-complementing 2 (ERCC2)more » gene from the previously described human DNA repair gene cluster at 19q13.2-q13.3. Direct transfer of a cosmid bearing the ERCC2 gene conferred UV resistance to XP-D cells.« less

Optical Design of Adaptive Optics Confocal Scanning Laser Ophthalmoscope with Two Deformable Mirrors.

PubMed

Yang, Jinsheng; Wang, Yuanyuan; Rao, Xuejun; Wei, Ling; Li, Xiqi; He, Yi

2017-01-01

We describe the optical design of a confocal scanning laser ophthalmoscope with two deformable mirrors. Spherical mirrors are used for pupil relay. Defocus aberration of the human eye is corrected by a Badal focusing structure and astigmatism aberration is corrected by a deformable mirror. The main optical system achieves a diffraction-limited performance through the entire scanning field (6 mm pupil, 3 degrees on pupil plane). The performance of the optical system, with correction of defocus and astigmatism, is also evaluated.

Atomic force microscopy analysis of human cornea surface after UV (λ=266 nm) laser irradiation

NASA Astrophysics Data System (ADS)

Spyratou, E.; Makropoulou, M.; Moutsouris, K.; Bacharis, C.; Serafetinides, A. A.

2009-07-01

Efficient cornea reshaping by laser irradiation for correcting refractive errors is still a major issue of interest and study. Although the excimer laser wavelength of 193 nm is generally recognized as successful in ablating corneal tissue for myopia correction, complications in excimer refractive surgery leads to alternative laser sources and methods for efficient cornea treatment. In this work, ablation experiments of human donor cornea flaps were conducted with the 4th harmonic of an Nd:YAG laser, with different laser pulses. AFM analysis was performed for examination of the ablated cornea flap morphology and surface roughness.

First comparative approach to touchscreen-based visual object-location paired-associates learning in humans (Homo sapiens) and a nonhuman primate (Microcebus murinus).

PubMed

Schmidtke, Daniel; Ammersdörfer, Sandra; Joly, Marine; Zimmermann, Elke

2018-05-10

A recent study suggests that a specific, touchscreen-based task on visual object-location paired-associates learning (PAL), the so-called Different PAL (dPAL) task, allows effective translation from animal models to humans. Here, we adapted the task to a nonhuman primate (NHP), the gray mouse lemur, and provide first evidence for the successful comparative application of the task to humans and NHPs. Young human adults reach the learning criterion after considerably less sessions (one order of magnitude) than young, adult NHPs, which is likely due to faster and voluntary rejection of ineffective learning strategies in humans and almost immediate rule generalization. At criterion, however, all human subjects solved the task by either applying a visuospatial rule or, more rarely, by memorizing all possible stimulus combinations and responding correctly based on global visual information. An error-profile analysis in humans and NHPs suggests that successful learning in NHPs is comparably based either on the formation of visuospatial associative links or on more reflexive, visually guided stimulus-response learning. The classification in the NHPs is further supported by an analysis of the individual response latencies, which are considerably higher in NHPs classified as spatial learners. Our results, therefore, support the high translational potential of the standardized, touchscreen-based dPAL task by providing first empirical and comparable evidence for two different cognitive processes underlying dPAL performance in primates. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

75 FR 22815 - Impact of Dissolvable Tobacco Use on Public Health; Request for Comments

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-30

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0123] Impact of Dissolvable Tobacco Use on Public Health; Request for Comments Correction In notice document 2010-6216 beginning on page 13556 in the issue of Monday, March 22, 2010, make the following correction...

76 FR 79701 - Bristol-Myers Squibb Co. et al.; Withdrawal of Approval of 70 New Drug Applications and 97...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-22

...: Florine Purdie, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0411... Drug Applications; Correction AGENCY: Food and Drug Administration, HHS. ACTION: Notice; correction...

76 FR 64951 - Apothecon et al.; Withdrawal of Approval of 103 New Drug Applications and 35 Abbreviated New Drug...

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75 FR 53701 - Clinical Studies of Safety and Effectiveness of Orphan Products Research Project Grant (R01...

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76 FR 37291 - Food Labeling; Calorie Labeling of Articles of Food in Vending Machines; Correction

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2011-06-27

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 101 [Docket No. FDA-2011-F-0171] Food Labeling; Calorie Labeling of Articles of Food in Vending Machines; Correction... certain articles of food sold from vending machines. The document published with several errors including...

77 FR 42510 - Notice of Inventory Completion: New York University College of Dentistry, New York, NY; Correction

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77 FR 9528 - Animal Drugs, Feeds, and Related Products; N-Methyl-2-Pyrrolidone; Correction

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2012-02-17

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78 FR 54568 - General Enforcement Regulations

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2013-09-05

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 1 General Enforcement Regulations CFR Correction 0 In Title 21 of the Code of Federal Regulations, Parts 1 to 199, revised as of April 1, 2013, on page 7, in Sec. 1.20, the introductory text is corrected to read as...

78 FR 79299 - New Animal Drugs for Use in Animal Feeds; Bambermycins; Correction

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2013-12-30

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 558 [Docket No. FDA-2013-N-0002] New Animal Drugs for Use in Animal Feeds; Bambermycins; Correction AGENCY: Food and... amended the animal drug regulations to remove dairy replacement heifers from the pasture cattle class for...

76 FR 16532 - New Animal Drugs; Change of Sponsor's Name and Address; Corrections

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2011-03-24

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Parts 510 and 529... made to improve the accuracy of the animal drug regulations. List of Subjects 21 CFR Part 510... Part 529 Animal drugs. Accordingly, 21 CFR parts 510 and 529 are corrected by making the following...

42 CFR 1001.1401 - Violations of PPS corrective action.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 5 2010-10-01 2010-10-01 false Violations of PPS corrective action. 1001.1401 Section 1001.1401 Public Health OFFICE OF INSPECTOR GENERAL-HEALTH CARE, DEPARTMENT OF HEALTH AND HUMAN... documented history of criminal, civil or administrative wrongdoing (The lack of any prior record is to be...

77 FR 19534 - Medical Devices; Immunology and Microbiology Devices; Classification of Norovirus Serological...

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2012-04-02

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78 FR 78796 - Supplemental Applications Proposing Labeling Changes for Approved Drugs and Biological Products...

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2013-12-27

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78 FR 24422 - Meeting of the President's Council on Fitness, Sports, and Nutrition; Correction

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2013-04-25

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76 FR 25694 - Meeting of the President's Council on Fitness, Sports, and Nutrition; Correction

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2011-05-05

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77 FR 12598 - Notice Correction; A Multi-Center International Hospital-Based Case-Control Study of Lymphoma in...

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2012-03-01

... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health Notice Correction; A Multi-Center International Hospital-Based Case-Control Study of Lymphoma in Asia (AsiaLymph) (NCI) The Federal... project titled, ``A multi-center international hospital-based case-control study of lymphoma in Asia (Asia...

45 CFR 262.6 - What happens if a State does not demonstrate reasonable cause?

Code of Federal Regulations, 2010 CFR

2010-10-01

... reasonable cause? 262.6 Section 262.6 Public Welfare Regulations Relating to Public Welfare OFFICE OF FAMILY ASSISTANCE (ASSISTANCE PROGRAMS), ADMINISTRATION FOR CHILDREN AND FAMILIES, DEPARTMENT OF HEALTH AND HUMAN... cause? (a) A State may accept the penalty or enter into a corrective compliance plan that will correct...

45 CFR 261.53 - May a State correct the problem before incurring a penalty?

Code of Federal Regulations, 2010 CFR

2010-10-01

... 45 Public Welfare 2 2010-10-01 2010-10-01 false May a State correct the problem before incurring a penalty? 261.53 Section 261.53 Public Welfare Regulations Relating to Public Welfare OFFICE OF FAMILY ASSISTANCE (ASSISTANCE PROGRAMS), ADMINISTRATION FOR CHILDREN AND FAMILIES, DEPARTMENT OF HEALTH AND HUMAN...

76 FR 32367 - Draft Guidance for Clinical Investigators, Industry, and FDA Staff: Financial Disclosure by...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-06

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-1999-D-0742 (formerly Docket No. 1999D-4396)] Draft Guidance for Clinical Investigators, Industry, and FDA Staff...: Notice; correction. SUMMARY: The Food and Drug Administration (FDA) is correcting a notice that appeared...

77 FR 51579 - Meetings of Humanities Panel; Correction

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-24

... Voyatzis, Committee Management Officer, at (202) 606-8322. Correction In the Federal Register of August 14... replace with: 9. Date: September 24, 2012. Time: 8:30 a.m. to 5:00 p.m. Room: 315. This meeting will discuss applications for the Bridging Cultures at Community Colleges: Request for Proposals for a...

Case Management in Community Corrections: Current Status and Future Directions

ERIC Educational Resources Information Center

Day, Andrew; Hardcastle, Lesley; Birgden, Astrid

2012-01-01

Case management is commonly regarded as the foundation of effective service provision across a wide range of human service settings. This article considers the case management that is offered to clients of community corrections, identifying the distinctive features of case management in this particular setting, and reviewing the empirical evidence…

Citizens' perceptions of the presence and health risks of synthetic chemicals in food: results of an online survey in Spain.

PubMed

Pumarega, José; Larrea, Cristina; Muñoz, Araceli; Pallarès, Natàlia; Gasull, Magda; Rodríguez, Giselle; Jariod, Manel; Porta, Miquel

To explore factors influencing perceptions and viewpoints on the responsibility for the presence of toxic substances in food, on enforcement of laws and regulations that control human exposure to toxic substances in food, and on the effectiveness of such regulations. An online survey was completed by 740 individuals from several parts of Spain (median age, 47 years; 67% were women; 70% had completed university studies). Over 87% of respondents said that it was possible that throughout their lives they could have accumulated in their body toxic substances potentially dangerous to their health. The attribution of the responsibility for toxic substances in food to a larger number of social groups was more frequent among respondents who consulted information about the problem more often (odds ratio [OR]: 1.92), who correctly identified factors that increase the likelihood of toxic substances in food being harmful to human health (OR: 2.86), who better knew the health problems that may be caused by such substances (OR: 2.48), and who recognised more food groups that tend to have concentrations of toxic substances potentially harmful to health (OR: 2.92) (all p values <0.001). Women were 65% less likely than men to answer that regulations on toxic substances in food are effective (p<0.001); and so were participants who identified more food groups with potentially toxic concentrations. Among study participants there was a widespread scepticism and distrust towards the enforcement and effectiveness of laws and regulations that in Spain aim to control human exposure to toxic substances in food. Copyright © 2017 SESPAS. Publicado por Elsevier España, S.L.U. All rights reserved.

Liquid Crystal on Silicon Wavefront Corrector

NASA Technical Reports Server (NTRS)

Pouch, John; Miranda, Felix; Wang, Xinghua; Bos, Philip, J.

2004-01-01

A low cost, high resolution, liquid crystal on silicon, spatial light modulator has been developed for the correction of huge aberrations in an optical system where the polarization dependence and the chromatic nature are tolerated. However, the overall system performance suggests that this device is also suitable for real time correction of aberration in human eyes. This device has a resolution of 1024 x 768, and is driven by an XGA display driver. The effective stroke length of the device is 700 nm and 2000 nm for the visible and IR regions of the device, respectively. The response speeds are 50 Hz and 5 Hz, respectively, which are fast enough for real time adaptive optics for aberrations in human eyes. By modulating a wavefront of 2 pi, this device can correct for arbitrary high order wavefront aberrations since the 2-D pixel array is independently controlled by the driver. The high resolution and high accuracy of the device allow for diffraction limited correction of the tip and tilt or defocus without an additional correction loop. We have shown that for every wave of aberration, an 8 step blazed grating is required to achieve high diffraction efficiency around 80%. In light of this, up to 125 waves peak to valley of tip and tilt can be corrected if we choose the simplest aberration. Corrections of 34 waves of aberration, including high order Zernicke terms in a high magnification telescope, to diffraction limited performance (residual wavefront aberration less than 1/30 lambda at 632.8 nm) have been observed at high efficiency.

The 'temporal effect' in hominids: Reinvestigating the nature of support for a chimp-human clade in bone morphology.

PubMed

Pearson, Alannah; Groves, Colin; Cardini, Andrea

2015-11-01

In 2004, an analysis by Lockwood and colleagues of hard-tissue morphology, using geometric morphometrics on the temporal bone, succeeded in recovering the correct phylogeny of living hominids without resorting to potentially problematic methods for transforming continuous shape variables into meristic characters. That work has increased hope that by using modern analytical methods and phylogenetically informative anatomical data we might one day be able to accurately infer the relationships of hominins, including the closest extinct relatives of modern humans. In the present study, using 3D virtually generated models of the hominid temporal bone and a larger suite of geometric morphometric and comparative techniques, we have re-examined the evidence for a Pan-Homo clade. Despite differences in samples, as well as the type of raw data, the effect of measurement error (and especially landmark digitization by a different operator), but also a broader perspective brought in by our diverse set of approaches, our reanalysis largely supports Lockwood and colleagues' original results. However, by focusing not only mainly on shape (as in the original 2004 analysis) but also on size and 'size-corrected' (non-allometric) shape, we demonstrate that the strong phylogenetic signal in the temporal bone is largely related to similarities in size. Thus, with this study, we are not suggesting the use of a single 'character', such as size, for phylogenetic inference, but we do challenge the common view that shape, with its highly complex and multivariate nature, is necessarily more phylogenetically informative than size and that actually size and size-related shape variation (i.e., allometry) confound phylogenetic inference based on morphology. This perspective may in fact be less generalizable than often believed. Thus, while we confirm the original findings by Lockwood et al., we provide a deep reinterpretation of their nature and potential implications for hominid phylogenetics and we show how crucial it is not to overlook size in geometric morphometric analyses. Copyright © 2015 Elsevier Ltd. All rights reserved.