Multiple functions of the E3 ubiquitin ligase CHIP in immunity.

PubMed

Zhan, Shaohua; Wang, Tianxiao; Ge, Wei

2017-09-03

The carboxyl terminal of Hsp70-interacting protein (CHIP) is an E3 ubiquitin ligase that plays a pivotal role in the protein quality control system by shifting the balance of the folding-refolding machinery toward the degradative pathway. However, the precise mechanisms by which nonnative proteins are selected for degradation by CHIP either directly or indirectly via chaperone Hsp70 or Hsp90 are still not clear. In this review, we aim to provide a comprehensive model of the mechanism by which CHIP degrades its substrate in a chaperone-dependent or direct manner. In addition, through tight regulation of the protein level of its substrates, CHIP plays important roles in many physiological and pathological conditions, including cancers, neurological disorders, cardiac diseases, bone metabolism, immunity, and so on. Nonetheless, the precise mechanisms underlying the regulation of the immune system by CHIP are still poorly understood despite accumulating developments in our understanding of the regulatory roles of CHIP in both innate and adaptive immune responses. In this review, we also aim to provide a view of CHIP-mediated regulation of immune responses and the signaling pathways involved in the model described. Finally, we discuss the roles of CHIP in immune-related diseases.

The Possibility of Improved and Higher Tc Superconductors in Hybrid Systems

DTIC Science & Technology

2014-10-15

Approved for public release; distribution is unlimited. of the oxygen sub-lattice precisely in thin films and heterostrutures; which plays a pivotal role...to influence the structure-property affair in complex oxide thin films. We have focused our study to effectively control the oxygen position...that by varying precisely the thickness of SCO layers grown on SrTiO3, one can re-arrange the oxygen ions. In particular, we show that it is possible

Phosphatidic acid and neurotransmission.

PubMed

Raben, Daniel M; Barber, Casey N

2017-01-01

Lipids play a vital role in the health and functioning of neurons and interest in the physiological role of neuronal lipids is certainly increasing. One neuronal function in which neuronal lipids appears to play key roles in neurotransmission. Our understanding of the role of lipids in the synaptic vesicle cycle and neurotransmitter release is becoming increasingly more important. Much of the initial research in this area has highlighted the major roles played by the phosphoinositides (PtdIns), diacylglycerol (DAG), and phosphatidic acid (PtdOH). Of these, PtdOH has not received as much attention as the other lipids although its role and metabolism appears to be extremely important. This lipid has been shown to play a role in modulating both exocytosis and endocytosis although its precise role in either process is not well defined. The currently evidence suggest this lipid likely participates in key processes by altering membrane architecture necessary for membrane fusion, mediating the penetration of membrane proteins, serving as a precursor for other important SV cycling lipids, or activating essential enzymes. In this review, we address the sources of PtdOH, the enzymes involved in its production, the regulation of these enzymes, and its potential roles in neurotransmission in the central nervous system. Copyright © 2016 Elsevier Ltd. All rights reserved.

Induced Pluripotent Stem Cells: at the Heart of Cardiovascular Precision Medicine

PubMed Central

Chen, Ian Y.; Matsa, Elena; Wu, Joseph C.

2018-01-01

The advent of human induced pluripotent stem cell (hiPSC) technology has revitalized much of the efforts within the past decade to more fully realize the potential of human embryonic stem cells (hESCs). Adding to the possibility of generating unlimited supplies of any cell types of interest, the hiPSC technology now enables the derivation of cells with patient-specific phenotypes. With the Precision Medicine Initiative, it is clear that the hiPSC technology will play a vital role in the advancement of cardiovascular research and medicine. This review summarizes the tremendous and continuing progress that has been made in the field of hiPSC technology, with particular emphasis on cardiovascular disease modeling and drug development. Wherever appropriate, the growing roles of hiPSC technology in the practice of precision medicine will be specifically discussed. PMID:27009425

Analyzing Water's Optical Absorption

NASA Technical Reports Server (NTRS)

2002-01-01

A cooperative agreement between World Precision Instruments (WPI), Inc., and Stennis Space Center has led the UltraPath(TM) device, which provides a more efficient method for analyzing the optical absorption of water samples at sea. UltraPath is a unique, high-performance absorbance spectrophotometer with user-selectable light path lengths. It is an ideal tool for any study requiring precise and highly sensitive spectroscopic determination of analytes, either in the laboratory or the field. As a low-cost, rugged, and portable system capable of high- sensitivity measurements in widely divergent waters, UltraPath will help scientists examine the role that coastal ocean environments play in the global carbon cycle. UltraPath(TM) is a trademark of World Precision Instruments, Inc. LWCC(TM) is a trademark of World Precision Instruments, Inc.

Results From PAPER/HERA

NASA Astrophysics Data System (ADS)

Pober, Jonathan C.

2018-05-01

The Precision Array for Probing the Epoch of Reionization (PAPER) was a first-generation 21 cm cosmology experiment with the specific goal of detecting the power spectrum of the 21 cm emission from the Epoch of Reionization. Analysis of PAPER data is still ongoing, but lessons learned from PAPER to date have played a critical role in designing the next-generation Hydrogen Epoch of Reionization Array (HERA) experiment. This article reviews five key design choices made by PAPER: use of a non-imaging configuration, redundancy, short baselines, small antenna elements, and a large instantaneous bandwidth. We describe the impact of these choices and the role they played in designing HERA.

Research on the impact factors of GRACE precise orbit determination by dynamic method

NASA Astrophysics Data System (ADS)

Guo, Nan-nan; Zhou, Xu-hua; Li, Kai; Wu, Bin

2018-07-01

With the successful use of GPS-only-based POD (precise orbit determination), more and more satellites carry onboard GPS receivers to support their orbit accuracy requirements. It provides continuous GPS observations in high precision, and becomes an indispensable way to obtain the orbit of LEO satellites. Precise orbit determination of LEO satellites plays an important role for the application of LEO satellites. Numerous factors should be considered in the POD processing. In this paper, several factors that impact precise orbit determination are analyzed, namely the satellite altitude, the time-variable earth's gravity field, the GPS satellite clock error and accelerometer observation. The GRACE satellites provide ideal platform to study the performance of factors for precise orbit determination using zero-difference GPS data. These factors are quantitatively analyzed on affecting the accuracy of dynamic orbit using GRACE observations from 2005 to 2011 by SHORDE software. The study indicates that: (1) with the altitude of the GRACE satellite is lowered from 480 km to 460 km in seven years, the 3D (three-dimension) position accuracy of GRACE satellite orbit is about 3˜4 cm based on long spans data; (2) the accelerometer data improves the 3D position accuracy of GRACE in about 1 cm; (3) the accuracy of zero-difference dynamic orbit is about 6 cm with the GPS satellite clock error products in 5 min sampling interval and can be raised to 4 cm, if the GPS satellite clock error products with 30 s sampling interval can be adopted. (4) the time-variable part of earth gravity field model improves the 3D position accuracy of GRACE in about 0.5˜1.5 cm. Based on this study, we quantitatively analyze the factors that affect precise orbit determination of LEO satellites. This study plays an important role to improve the accuracy of LEO satellites orbit determination.

High-Precision 40Ar/39Ar dating of the Deccan Traps

NASA Astrophysics Data System (ADS)

Sprain, C. J.; Renne, P. R.; Fendley, I.; Pande, K.; Self, S.; Vanderkluysen, L.; Richards, M. A.

2017-12-01

Almost forty years ago it was first hypothesized that greenhouse gases emitted from the Deccan Traps (DT) played a role in the Cretaceous-Paleogene boundary (KPB) mass extinction (McLean 1979, 1980, 1985). At that time, this hypothesis was dismissed due to insufficient geochronology and new evidence that a bolide impact coincided with the KPB. Since then, evidence such as records of protracted extinction and climate change in the Late Cretaceous, in addition to new high-precision geochronology of the DT, has bolstered the Deccan hypothesis. Recently, many models have been produced to simulate how DT volcanism may have perturbed global ecosystems. However, modeled outcomes are largely dependent upon variables such as the amount and species of gas released and the tempo of eruptions, which are not well constrained (Self et al., 2014). To better constrain climatic models and better understand the role DT volcanism played in the KPB extinction, we developed a high-precision geochronologic framework defining the timing and tempo of DT eruptions within the Western Ghats using high-precision 40Ar/39Ar geochronology. Our new results show that the DT erupted relatively continuously starting 66.4 Ma and extending to at least 65.3 Ma with no hiatuses longer than 50 ka, invalidating the concept of three discrete eruption pulses in the Western Ghats (Chenet et al., 2007, 2009; Keller et al., 2008). Our new data further provide the first precise location of the KPB within the DT sequence and place this boundary at or near the Lonavala-Wai subgroup transition, roughly coincident with major changes in eruption frequency, flow-field volumes, and extent of crustal magma contamination. Taken together, these results suggest that a state shift occurred in the DT magmatic system around the time of the Chicxulub impact, consistent with the impact triggering hypothesis of Richards et al. (2015). Our work further shows that over 80% of the estimated volume of the DT within the Western Ghats erupted in 600 ka; however, 70% of this volume, erupted after the KPB calling for a reassessment of the role of DT volcanism played in the KPB mass extinction and subsequent recovery. It is important to note that current volume estimates are likely to change as we work to improve understanding of the distribution of chemical formations, both on and offshore.

In-Service Training Programmes for Inclusive Education in Serbia--Offer and Implementation

ERIC Educational Resources Information Center

Matovic, Nataša; Spasenovic, Vera

2015-01-01

The initial education and in-service training of all educators, particularly teachers, play a vital role in strengthening competences necessary for implementing inclusive educational practice. This paper analyses offered and implemented inservice training programmes for educators in the field of inclusive education or, more precisely, for working…

Omics for Understanding the Gut-Liver-Microbiome Axis and Precision Medicine

USDA-ARS?s Scientific Manuscript database

Human metabolic disease opens a new view to understanding the contribution of the intestinal microbiome to drug metabolism and drug-induced toxicity in gut-liver function. Gut microbiota, a key determinant of intestinal inflammation, also plays a direct role in chronic inflammation and liver disease...

A Computational Model of Linguistic Humor in Puns

ERIC Educational Resources Information Center

Kao, Justine T.; Levy, Roger; Goodman, Noah D.

2016-01-01

Humor plays an essential role in human interactions. Precisely what makes something funny, however, remains elusive. While research on natural language understanding has made significant advancements in recent years, there has been little direct integration of humor research with computational models of language understanding. In this paper, we…

Quantum algorithms for quantum field theories.

PubMed

Jordan, Stephen P; Lee, Keith S M; Preskill, John

2012-06-01

Quantum field theory reconciles quantum mechanics and special relativity, and plays a central role in many areas of physics. We developed a quantum algorithm to compute relativistic scattering probabilities in a massive quantum field theory with quartic self-interactions (φ(4) theory) in spacetime of four and fewer dimensions. Its run time is polynomial in the number of particles, their energy, and the desired precision, and applies at both weak and strong coupling. In the strong-coupling and high-precision regimes, our quantum algorithm achieves exponential speedup over the fastest known classical algorithm.

Molecular Imaging and Precision Medicine in Uterine and Ovarian Cancers.

PubMed

Zukotynski, Katherine A; Kim, Chun K

2017-10-01

Gynecologic cancer is a heterogeneous group of diseases both functionally and morphologically. Today, PET coupled with computed tomography (PET/CT) or PET/MR imaging play a central role in the precision medicine algorithm of patients with gynecologic malignancy. In particular, PET/CT and PET/MR imaging are molecular imaging techniques that not only are useful tools for initial staging and restaging but provide anatomofunctional insight and can serve as predictive and prognostic biomarkers of response in patients with gynecologic malignancy. Copyright © 2017 Elsevier Inc. All rights reserved.

The role of fungi in diseases of the nose and sinuses

PubMed Central

Schlosser, Rodney J.

2012-01-01

Background: Human exposure to fungal elements is inevitable, with normal respiration routinely depositing fungal hyphae within the nose and paranasal sinuses. Fungal species can cause sinonasal disease, with clinical outcomes ranging from mild symptoms to intracranial invasion and death. There has been much debate regarding the precise role fungal species play in sinonasal disease and optimal treatment strategies. Methods: A literature review of fungal diseases of the nose and sinuses was conducted. Results: Presentation, diagnosis, and current management strategies of each recognized form of fungal rhinosinusitis was reviewed. Conclusion: Each form of fungal rhinosinusitis has a characteristic presentation and clinical course, with the immune status of the host playing a critical pathophysiological role. Accurate diagnosis and targeted treatment strategies are necessary to achieve optimal outcomes. PMID:23168148

Disruption of the Aspergillus fumigatus ECM33 homologue results in rapid conidial germination, antifungal resistance and hypervirulence.

PubMed

Romano, Jacob; Nimrod, Guy; Ben-Tal, Nir; Shadkchan, Yona; Baruch, Koti; Sharon, Haim; Osherov, Nir

2006-07-01

The ECM33/SPS2 family of glycosylphosphatidylinositol-anchored proteins plays an important role in maintaining fungal cell wall integrity and virulence. However, the precise molecular role of these proteins is unknown. In this work, AfuEcm33, the gene encoding the ECM33 homologue in the important pathogenic fungus Aspergillus fumigatus, has been cloned and its function analysed. It is shown that disruption of AfuEcm33 results in rapid conidial germination, increased cell-cell adhesion, resistance to the antifungal agent caspofungin and increased virulence in an immunocompromised mouse model for disseminated aspergillosis. These results suggest that the protein encoded by AfuEcm33 is involved in key aspects of cell wall morphogenesis and plays an important role in A. fumigatus virulence.

Experiential Learning of Robotics Fundamentals Based on a Case Study of Robot-Assisted Stereotactic Neurosurgery

ERIC Educational Resources Information Center

Faria, Carlos; Vale, Carolina; Machado, Toni; Erlhagen, Wolfram; Rito, Manuel; Monteiro, Sérgio; Bicho, Estela

2016-01-01

Robotics has been playing an important role in modern surgery, especially in procedures that require extreme precision, such as neurosurgery. This paper addresses the challenge of teaching robotics to undergraduate engineering students, through an experiential learning project of robotics fundamentals based on a case study of robot-assisted…

Off and back-on again: a tumor suppressor's tale.

PubMed

Acosta, Jonuelle; Wang, Walter; Feldser, David M

2018-06-01

Tumor suppressor genes play critical roles orchestrating anti-cancer programs that are both context dependent and mechanistically diverse. Beyond canonical tumor suppressive programs that control cell division, cell death, and genome stability, unexpected tumor suppressor gene activities that regulate metabolism, immune surveillance, the epigenetic landscape, and others have recently emerged. This diversity underscores the important roles these genes play in maintaining cellular homeostasis to suppress cancer initiation and progression, but also highlights a tremendous challenge in discerning precise context-specific programs of tumor suppression controlled by a given tumor suppressor. Fortunately, the rapid sophistication of genetically engineered mouse models of cancer has begun to shed light on these context-dependent tumor suppressor activities. By using techniques that not only toggle "off" tumor suppressor genes in nascent tumors, but also facilitate the timely restoration of gene function "back-on again" in disease specific contexts, precise mechanisms of tumor suppression can be revealed in an unbiased manner. This review discusses the development and implementation of genetic systems designed to toggle tumor suppressor genes off and back-on again and their potential to uncover the tumor suppressor's tale.

Stimulus-induced, sleep-bound, focal seizures: a case report.

PubMed

Siclari, Francesca; Nobili, Lino; Lo Russo, Giorgio; Moscato, Alessio; Buck, Alfred; Bassetti, Claudio L; Khatami, Ramin

2011-12-01

In nocturnal frontal lobe epilepsy (NFLE), seizures occur almost exclusively during NREM sleep. Why precisely these seizures are sleep-bound remains unknown. Studies of patients with nonlesional familial forms of NFLE have suggested the arousal system may play a major role in their pathogenesis. We report the case of a patient with pharmaco-resistant, probably cryptogenic form of non-familial NFLE and strictly sleep-bound seizures that could be elicited by alerting stimuli and were associated with ictal bilateral thalamic and right orbital-insular hyperperfusion on SPECT imaging. Case report. University Hospital Zurich. One patient with pharmaco-resistant epilepsy. This case shows that the arousal system plays a fundamental role also in cryptogenic non-familial forms of NFLE.

A quantum network of clocks

NASA Astrophysics Data System (ADS)

Kómár, P.; Kessler, E. M.; Bishof, M.; Jiang, L.; Sørensen, A. S.; Ye, J.; Lukin, M. D.

2014-08-01

The development of precise atomic clocks plays an increasingly important role in modern society. Shared timing information constitutes a key resource for navigation with a direct correspondence between timing accuracy and precision in applications such as the Global Positioning System. By combining precision metrology and quantum networks, we propose a quantum, cooperative protocol for operating a network of geographically remote optical atomic clocks. Using nonlocal entangled states, we demonstrate an optimal utilization of global resources, and show that such a network can be operated near the fundamental precision limit set by quantum theory. Furthermore, the internal structure of the network, combined with quantum communication techniques, guarantees security both from internal and external threats. Realization of such a global quantum network of clocks may allow construction of a real-time single international time scale (world clock) with unprecedented stability and accuracy.

Clamping characteristics study on different types of clamping unit

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

Jiao, Zhiwei; Liu, Haichao; Xie, Pengcheng

2015-05-22

Plastic products are becoming more and more widely used in aerospace, IT, digital electronics and many other fields. With the development of technology, the requirement of product precision is getting higher and higher. However, type and working performance of clamping unit play a decisive role in product precision. Clamping characteristics of different types of clamping unit are discussed in this article, which use finite element numerical analysis method through the software ABAQUS to study the clamping uniformity, and detect the clamping force repeatability precision. The result shows that compared with toggled three-platen clamping unit, clamping characteristics of internal circulation two-platenmore » clamping unit are better, for instance, its mold cavity deformation and force that bars and mold parting surface suffered are more uniform, and its clamping uniformity and repeatability precision is also better.« less

Nursing implications of personalized and precision medicine.

PubMed

Vorderstrasse, Allison A; Hammer, Marilyn J; Dungan, Jennifer R

2014-05-01

Identify and discuss the nursing implications of personalized and precision oncology care. PubMed, CINAHL. The implications in personalized and precision cancer nursing care include interpretation and clinical use of novel and personalized information including genetic testing; patient advocacy and support throughout testing, anticipation of results and treatment; ongoing chronic monitoring; and support for patient decision-making. Attention must also be given to the family and ethical implications of a personalized approach to care. Nurses face increasing challenges and opportunities in communication, support, and advocacy for patients given the availability of advanced testing, care and treatment in personalized and precision medicine. Nursing education and continuing education, clinical decision support, and health systems changes will be necessary to provide personalized multidisciplinary care to patients, in which nurses play a key role. Copyright © 2014 Elsevier Inc. All rights reserved.

Precision CMB Measurements from Long Duration Stratospheric Balloons: Towards B-modes and Inflation

NASA Astrophysics Data System (ADS)

Jones, William C.

2013-01-01

Observations of the Cosmic Microwave Background (CMB) have played a leading role in establishing an understanding of the structure and evolution of the Universe on the largest scales. This achievement has been enabled by a series of extremely successful experiments, coupled with the simplicity of the relationship between the cosmological theory and data. Antarctic experiments, including both balloon-borne telescopes and instruments at the South Pole, have played a key role in realizing the scientific potential of the CMB, from the characterization of the temperature anisotropies to the detection and study of the polarized component. Current and planned Antarctic long duration balloon experiments will extend this heritage of discovery to test theories of cosmic genesis through sensitive polarized surveys of the millimeter-wavelength sky. In this paper we will review the pivotal role that Antarctic balloon borne experiments have played in transforming our understanding of the Universe, and describe the scientific goals and technical approach of current and future missions.

What to use to express the variability of data: Standard deviation or standard error of mean?

PubMed

Barde, Mohini P; Barde, Prajakt J

2012-07-01

Statistics plays a vital role in biomedical research. It helps present data precisely and draws the meaningful conclusions. While presenting data, one should be aware of using adequate statistical measures. In biomedical journals, Standard Error of Mean (SEM) and Standard Deviation (SD) are used interchangeably to express the variability; though they measure different parameters. SEM quantifies uncertainty in estimate of the mean whereas SD indicates dispersion of the data from mean. As readers are generally interested in knowing the variability within sample, descriptive data should be precisely summarized with SD. Use of SEM should be limited to compute CI which measures the precision of population estimate. Journals can avoid such errors by requiring authors to adhere to their guidelines.

Bringing Definitions into High Definition

ERIC Educational Resources Information Center

Mason, John

2010-01-01

Why do definitions play such a central role in mathematics? It may seem obvious that precision about the terms one uses is necessary in order to use those terms reasonably (while reasoning). Definitions are chosen so as to be definite about the terms one uses, but also to make both the statement of, and the reasoning to justify, theorems as…

Clinical Use of AEVP- and AERP-Measures in Childhood Speech Disorders

ERIC Educational Resources Information Center

Maassen, Ben; Pasman, Jaco; Nijland, Lian; Rotteveel, Jan

2006-01-01

It has long been recognized that from the first months of life auditory perception plays a crucial role in speech and language development. Only in recent years, however, is the precise mechanism of auditory development and its interaction with the acquisition of speech and language beginning to be systematically revealed. This paper presents the…

Criteria for optimizing food composition tables in relation to studies of habitual food intakes.

PubMed

Joyanes, María; Lema, Lourdes

2006-01-01

The purpose of this study is to increase the accuracy, reliability, and precision of food composition data and, in consequence, better approximate nutrient intake estimations and recommendations. To do this it is necessary to specify and taken into account factors that play an important role in the variation of composition in order to avoid excessively broad dispersions and irregularities in data distributions. This implies the presentation of representative and, as consequence, extrapolable data, with nutritionally grounded confidence intervals. This study suggests a methodology that better approaches the accuracy, reliability, and precision of food composition data.

A subtle calculation method for nanoparticle’s molar extinction coefficient: The gift from discrete protein-nanoparticle system on agarose gel electrophoresis

NASA Astrophysics Data System (ADS)

Zhong, Ruibo; Yuan, Ming; Gao, Haiyang; Bai, Zhijun; Guo, Jun; Zhao, Xinmin; Zhang, Feng

2016-03-01

Discrete biomolecule-nanoparticle (NP) conjugates play paramount roles in nanofabrication, in which the key is to get the precise molar extinction coefficient of NPs. By making best use of the gift from a specific separation phenomenon of agarose gel electrophoresis (GE), amphiphilic polymer coated NP with exact number of bovine serum albumin (BSA) proteins can be extracted and further experimentally employed to precisely calculate the molar extinction coefficient of the NPs. This method could further benefit the evaluation and extraction of any other dual-component NP-containing bio-conjugates.

A role for lipid-mediated signaling in plant gravitropism.

PubMed

Smith, Caroline M; Desai, Mintu; Land, Eric S; Perera, Imara Y

2013-01-01

Gravitropism is a universal plant response. It is initiated by the sensing of the primary signal (mass or pressure), which is then converted into chemical signals that are transduced and propagated in a precise spatial and temporal fashion, resulting in a differential growth response. Our thesis is that membrane lipids and lipid-mediated signaling pathways play critical roles in the initial signaling and in the establishment of polarity. In this review, we highlight results from recent literature and discuss the major questions that remain unanswered.

A bio-physical basis of mathematics in synaptic function of the nervous system: a theory.

PubMed

Dempsher, J

1980-01-01

The purpose of this paper is to present a bio-physical basis of mathematics. The essence of the theory is that function in the nervous system is mathematical. The mathematics arises as a result of the interaction of energy (a wave with a precise curvature in space and time) and matter (a molecular or ionic structure with a precise form in space and time). In this interaction, both energy and matter play an active role. That is, the interaction results in a change in form of both energy and matter. There are at least six mathematical operations in a simple synaptic region. It is believed the form of both energy and matter are specific, and their interaction is specific, that is, function in most of the 'mind' and placed where it belongs - in nature and the synaptic regions of the nervous system; it results in both places from a precise interaction between energy (in a precise form) and matter ( in a precise structure).

Prospects for Precision Neutrino Cross Section Measurements

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

Harris, Deborah A.

2016-01-28

The need for precision cross section measurements is more urgent now than ever before, given the central role neutrino oscillation measurements play in the field of particle physics. The definition of precision is something worth considering, however. In order to build the best model for an oscillation experiment, cross section measurements should span a broad range of energies, neutrino interaction channels, and target nuclei. Precision might better be defined not in the final uncertainty associated with any one measurement but rather with the breadth of measurements that are available to constrain models. Current experience shows that models are better constrainedmore » by 10 measurements across different processes and energies with 10% uncertainties than by one measurement of one process on one nucleus with a 1% uncertainty. This article describes the current status of and future prospects for the field of precision cross section measurements considering the metric of how many processes, energies, and nuclei have been studied.« less

Promoter Melting Plays Critical Role in Lymphocyte Activation | Center for Cancer Research

Cancer.gov

Transcription in eukaryotic cells is a precisely timed ballet that consists of RNA polymerase II (pol II) recruitment to gene promoters, assembly of the multiprotein preinitiation complex, opening of the DNA, escape of pol II from the promoter, pol II pausing downstream, mRNA elongation, and, eventually, termination. The two main points of regulation are thought to be

Cellular Reprogramming, Genome Editing, and Alternative CRISPR Cas9 Technologies for Precise Gene Therapy of Duchenne Muscular Dystrophy

PubMed Central

Xu, Huaigeng

2017-01-01

In the past decade, the development of two innovative technologies, namely, induced pluripotent stem cells (iPSCs) and the CRISPR Cas9 system, has enabled researchers to model diseases derived from patient cells and precisely edit DNA sequences of interest, respectively. In particular, Duchenne muscular dystrophy (DMD) has been an exemplary monogenic disease model for combining these technologies to demonstrate that genome editing can correct genetic mutations in DMD patient-derived iPSCs. DMD is an X-linked genetic disorder caused by mutations that disrupt the open reading frame of the dystrophin gene, which plays a critical role in stabilizing muscle cells during contraction and relaxation. The CRISPR Cas9 system has been shown to be capable of targeting the dystrophin gene and rescuing its expression in in vitro patient-derived iPSCs and in vivo DMD mouse models. In this review, we highlight recent advances made using the CRISPR Cas9 system to correct genetic mutations and discuss how emerging CRISPR technologies and iPSCs in a combined platform can play a role in bringing a therapy for DMD closer to the clinic. PMID:28607562

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

Kramer, Michael; Jodrell Bank Centre for Astrophysics, University of Manchester, Manchester M13 9PL

The last years have seen continuing activities in the exploration of our understanding of gravity, motivated by results from precision cosmology and new precision astrophysical experiments. At the centre of attention lies the question as to whether general relativity is the correct theory of gravity. In answering this question, we work not only towards correctly interpreting the phenomenon of 'dark energy' but also towards the goal of achieving a quantum theory of gravity. In these efforts, the observations of pulsars, especially those in binary systems, play an important role. Pulsars do not only provide the only evidence for the existencemore » of gravitational waves so far, but they also provide precision tests of general relativity and alternative theories of gravity. This talk summarizes the current state-of-art in these experiments and looks into the future.« less

Coherent Doppler Lidar for Precision Navigation of Spacecrafts

NASA Technical Reports Server (NTRS)

Amzajerdian, Farzin; Pierrottet, Diego; Petway, Larry; Hines, Glenn; Lockhard, George; Barnes, Bruce

2011-01-01

A fiber-based coherent Doppler lidar, utilizing an FMCW technique, has been developed and its capabilities demonstrated through two successful helicopter flight test campaigns. This Doppler lidar is expected to play a critical role in future planetary exploration missions because of its ability in providing the necessary data for soft landing on the planetary bodies and for landing missions requiring precision navigation to the designated location on the ground. Compared with radars, the Doppler lidar can provide significantly higher precision velocity and altitude data at a much higher rate without concerns for measurement ambiguity or target clutter. Future work calls for testing the Doppler lidar onboard a rocket-powered free-flyer platform operating in a closed-loop with the vehicle s guidance, navigation, and control (GN&C) unit.

High Precision Prediction of Functional Sites in Protein Structures

PubMed Central

Buturovic, Ljubomir; Wong, Mike; Tang, Grace W.; Altman, Russ B.; Petkovic, Dragutin

2014-01-01

We address the problem of assigning biological function to solved protein structures. Computational tools play a critical role in identifying potential active sites and informing screening decisions for further lab analysis. A critical parameter in the practical application of computational methods is the precision, or positive predictive value. Precision measures the level of confidence the user should have in a particular computed functional assignment. Low precision annotations lead to futile laboratory investigations and waste scarce research resources. In this paper we describe an advanced version of the protein function annotation system FEATURE, which achieved 99% precision and average recall of 95% across 20 representative functional sites. The system uses a Support Vector Machine classifier operating on the microenvironment of physicochemical features around an amino acid. We also compared performance of our method with state-of-the-art sequence-level annotator Pfam in terms of precision, recall and localization. To our knowledge, no other functional site annotator has been rigorously evaluated against these key criteria. The software and predictive models are incorporated into the WebFEATURE service at http://feature.stanford.edu/wf4.0-beta. PMID:24632601

Leptin plays a catabolic role on articular cartilage.

PubMed

Bao, Jia-peng; Chen, Wei-ping; Feng, Jie; Hu, Peng-fei; Shi, Zhong-li; Wu, Li-dong

2010-10-01

Leptin has been shown to play a crucial role in the regulation of body weight. There is also evidence that this adipokine plays a key role in the process of osteoarthritis. However, the precise role of leptin on articular cartilage metabolism is not clear. We investigate the role of leptin on articular cartilage in vivo in this study. Recombinant rat leptin (100 μg) was injected into the knee joints of rats, 48 h later, messenger RNA (mRNA) expression and protein levels of basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), matrix metalloproteinases 2 and 9 (MMP-2, MMP-9), cathepsin D, and collagen II from articular cartilage were analyzed by real-time quantitative polymerase chain reaction (PCR) and western blot. Two important aggrecanases ADAMTS-4 and -5 (a disintegrin and metalloproteinase with thrombospondin motifs 4 and 5) were also analyzed by real-time quantitative PCR. Besides, articular cartilage was also assessed for proteoglycan/GAG content by Safranin O staining. Leptin significantly increased both gene and protein levels of MMP-2, MMP-9, cathepsin D, and collagen II, while decreased bFGF markedly in cartilage. Moreover, the gene expression of ADAMTS-4 and -5 were markedly increased, and histologically assessed depletion of proteoglycan in articular cartilage was observed after treatment with leptin. These results strongly suggest that leptin plays a catabolic role on cartilage metabolism and may be a disadvantage factor involve in the pathological process of OA.

NHE8 plays important roles in gastric mucosal protection

PubMed Central

Xu, Hua; Li, Jing; Chen, Huacong; Wang, Chunhui

2013-01-01

Sodium/hydrogen exchanger (NHE) 8 is an apically expressed membrane protein in the intestinal epithelial cells. It plays important roles in sodium absorption and bicarbonate secretion in the intestine. Although NHE8 mRNA has been detected in the stomach, the precise location and physiological role of NHE8 in the gastric glands remain unclear. In the current study, we successfully detected the expression of NHE8 in the glandular region of the stomach by Western blotting and located NHE8 protein at the apical membrane in the surface mucous cells by a confocal microscopic method. We also identified the expression of downregulated-in-adenoma (DRA) in the surface mucous cells in the stomach. Using NHE8−/− mice, we found that NHE8 plays little or no role in basal gastric acid production, yet NHE8−/− mice have reduced gastric mucosal surface pH and higher incidence of developing gastric ulcer. DRA expression was reduced significantly in the stomach in NHE8−/− mice. The propensity for gastric ulcer, reduced mucosal surface pH, and low DRA expression suggest that NHE8 is indirectly involved in gastric bicarbonate secretion and gastric mucosal protection. PMID:23220221

Epitaxial growth of aligned atomically precise chevron graphene nanoribbons on Cu(111).

PubMed

Teeter, Jacob D; Costa, Paulo S; Mehdi Pour, Mohammad; Miller, Daniel P; Zurek, Eva; Enders, Axel; Sinitskii, Alexander

2017-07-25

Atomically precise chevron graphene nanoribbons (GNRs) have been synthesized on Cu(111) substrates by the surface-assisted coupling of 6,11-dibromo-1,2,3,4-tetraphenyltriphenylene (C 42 Br 2 H 26 ) and thermal cyclodehydrogenation of the resulting polymer. The GNRs form on Cu(111) epitaxially along the 〈112〉 crystallographic directions, which was found to be in agreement with the computational results, and at lower temperatures than on Au(111). This work demonstrates that the substrate plays an important role in the on-surface synthesis of GNRs and can result in new assembly modes of GNR structures.

Lab Plays Central Role in Groundbreaking National Clinical Trial in Precision Medicine | Poster

Cancer.gov

The Molecular Characterization Laboratory lies at the heart of an ambitious new approach for testing cancer drugs that will use the newest tools of precision medicine to select the best treatment for individual patients based on the genetic makeup of their tumors. The protocol, called NCI-Molecular Analysis for Therapy Choice (NCI-MATCH), will start with tumor biopsies from as many as 3,000 patients to see if they have genetic defects for which a targeted cancer drug is available. Cancers will be treated based on their genetic profiles rather than by their location in the body, which is the conventional approach.

Precision Medicine and PET/Computed Tomography in Melanoma.

PubMed

Mena, Esther; Sanli, Yasemin; Marcus, Charles; Subramaniam, Rathan M

2017-10-01

Recent advances in genomic profiling and sequencing of melanoma have provided new insights into the development of the basis for molecular biology to more accurately subgroup patients with melanoma. The development of novel mutation-targeted and immunomodulation therapy as a major component of precision oncology has revolutionized the management and outcome of patients with metastatic melanoma. PET imaging plays an important role in noninvasively assessing the tumor biological behavior, to guide individualized treatment and assess response to therapy. This review summarizes the recent genomic discoveries in melanoma in the era of targeted therapy and their implications for functional PET imaging. Published by Elsevier Inc.

Satellite cells in human skeletal muscle plasticity

PubMed Central

Snijders, Tim; Nederveen, Joshua P.; McKay, Bryon R.; Joanisse, Sophie; Verdijk, Lex B.; van Loon, Luc J. C.; Parise, Gianni

2015-01-01

Skeletal muscle satellite cells are considered to play a crucial role in muscle fiber maintenance, repair and remodeling. Our knowledge of the role of satellite cells in muscle fiber adaptation has traditionally relied on in vitro cell and in vivo animal models. Over the past decade, a genuine effort has been made to translate these results to humans under physiological conditions. Findings from in vivo human studies suggest that satellite cells play a key role in skeletal muscle fiber repair/remodeling in response to exercise. Mounting evidence indicates that aging has a profound impact on the regulation of satellite cells in human skeletal muscle. Yet, the precise role of satellite cells in the development of muscle fiber atrophy with age remains unresolved. This review seeks to integrate recent results from in vivo human studies on satellite cell function in muscle fiber repair/remodeling in the wider context of satellite cell biology whose literature is largely based on animal and cell models. PMID:26557092

Pharmacogenomics and Global Precision Medicine in the Context of Adverse Drug Reactions: Top 10 Opportunities and Challenges for the Next Decade.

PubMed

Alessandrini, Marco; Chaudhry, Mamoonah; Dodgen, Tyren M; Pepper, Michael S

2016-10-01

In a move indicative of the enthusiastic support of precision medicine, the U.S. President Barack Obama announced the Precision Medicine Initiative in January 2015. The global precision medicine ecosystem is, thus, receiving generous support from the United States ($215 million), and numerous other governments have followed suit. In the context of precision medicine, drug treatment and prediction of its outcomes have been important for nearly six decades in the field of pharmacogenomics. The field offers an elegant solution for minimizing the effects and occurrence of adverse drug reactions (ADRs). The Clinical Pharmacogenetics Implementation Consortium (CPIC) plays an important role in this context, and it aims at specifically guiding the translation of clinically relevant and evidence-based pharmacogenomics research. In this forward-looking analysis, we make particular reference to several of the CPIC guidelines and their role in guiding the treatment of highly relevant diseases, namely cardiovascular disease, major depressive disorder, cancer, and human immunodeficiency virus, with a view to predicting and managing ADRs. In addition, we provide a list of the top 10 crosscutting opportunities and challenges facing the fields of precision medicine and pharmacogenomics, which have broad applicability independent of the drug class involved. Many of these opportunities and challenges pertain to infrastructure, study design, policy, and science culture in the early 21st century. Ultimately, rational pharmacogenomics study design and the acquisition of comprehensive phenotypic data that proportionately match the genomics data should be an imperative as we move forward toward global precision medicine.

Pharmacogenomics and Global Precision Medicine in the Context of Adverse Drug Reactions: Top 10 Opportunities and Challenges for the Next Decade

PubMed Central

Alessandrini, Marco; Chaudhry, Mamoonah; Dodgen, Tyren M.

2016-01-01

Abstract In a move indicative of the enthusiastic support of precision medicine, the U.S. President Barack Obama announced the Precision Medicine Initiative in January 2015. The global precision medicine ecosystem is, thus, receiving generous support from the United States ($215 million), and numerous other governments have followed suit. In the context of precision medicine, drug treatment and prediction of its outcomes have been important for nearly six decades in the field of pharmacogenomics. The field offers an elegant solution for minimizing the effects and occurrence of adverse drug reactions (ADRs). The Clinical Pharmacogenetics Implementation Consortium (CPIC) plays an important role in this context, and it aims at specifically guiding the translation of clinically relevant and evidence-based pharmacogenomics research. In this forward-looking analysis, we make particular reference to several of the CPIC guidelines and their role in guiding the treatment of highly relevant diseases, namely cardiovascular disease, major depressive disorder, cancer, and human immunodeficiency virus, with a view to predicting and managing ADRs. In addition, we provide a list of the top 10 crosscutting opportunities and challenges facing the fields of precision medicine and pharmacogenomics, which have broad applicability independent of the drug class involved. Many of these opportunities and challenges pertain to infrastructure, study design, policy, and science culture in the early 21st century. Ultimately, rational pharmacogenomics study design and the acquisition of comprehensive phenotypic data that proportionately match the genomics data should be an imperative as we move forward toward global precision medicine. PMID:27643672

Millisecond-timescale local network coding in the rat primary somatosensory cortex.

PubMed

Eldawlatly, Seif; Oweiss, Karim G

2011-01-01

Correlation among neocortical neurons is thought to play an indispensable role in mediating sensory processing of external stimuli. The role of temporal precision in this correlation has been hypothesized to enhance information flow along sensory pathways. Its role in mediating the integration of information at the output of these pathways, however, remains poorly understood. Here, we examined spike timing correlation between simultaneously recorded layer V neurons within and across columns of the primary somatosensory cortex of anesthetized rats during unilateral whisker stimulation. We used bayesian statistics and information theory to quantify the causal influence between the recorded cells with millisecond precision. For each stimulated whisker, we inferred stable, whisker-specific, dynamic bayesian networks over many repeated trials, with network similarity of 83.3±6% within whisker, compared to only 50.3±18% across whiskers. These networks further provided information about whisker identity that was approximately 6 times higher than what was provided by the latency to first spike and 13 times higher than what was provided by the spike count of individual neurons examined separately. Furthermore, prediction of individual neurons' precise firing conditioned on knowledge of putative pre-synaptic cell firing was 3 times higher than predictions conditioned on stimulus onset alone. Taken together, these results suggest the presence of a temporally precise network coding mechanism that integrates information across neighboring columns within layer V about vibrissa position and whisking kinetics to mediate whisker movement by motor areas innervated by layer V.

Role of regulatory T cell in the pathogenesis of inflammatory bowel disease.

PubMed

Yamada, Akiko; Arakaki, Rieko; Saito, Masako; Tsunematsu, Takaaki; Kudo, Yasusei; Ishimaru, Naozumi

2016-02-21

Regulatory T (Treg) cells play key roles in various immune responses. For example, Treg cells contribute to the complex pathogenesis of inflammatory bowel disease (IBD), which includes Crohn's disease and ulcerative colitis during onset or development of that disease. Many animal models of IBD have been used to investigate factors such as pathogenic cytokines, pathogenic bacteria, and T-cell functions, including those of Treg cells. In addition, analyses of patients with IBD facilitate our understanding of the precise mechanism of IBD. This review article focuses on the role of Treg cells and outlines the pathogenesis and therapeutic strategies of IBD based on previous reports.

Delusions and the Right Hemisphere: A Review of the Case for the Right Hemisphere as a Mediator of Reality-Based Belief.

PubMed

Gurin, Lindsey; Blum, Sonja

2017-01-01

Delusions are beliefs that remain fixed despite evidence that they are incorrect. Although the precise neural mechanism of delusional belief remains to be elucidated, there is a predominance of right-hemisphere lesions among patients with delusional syndromes accompanied by structural pathology, suggesting that right-hemisphere lesions, or networks with key nodes in the right hemisphere, may be playing a role. The authors discuss the potential theoretical basis and empiric support for a specific right-hemisphere role in delusion production, drawing on its roles in pragmatic communication; perceptual integration; attentional surveillance and anomaly/novelty detection; and belief updating.

"Living theatre, theatre of life".

PubMed

Wenzel, E

1987-09-01

Young people love to play theatre--in one way or another. They like to play with behaviours, costumes, words, communication patterns, etc.; they like to disguise themselves, to create certain spheres and scenes of drama and tragedy, excitement and extacy, satire and irony, morals and decadence. Due to the particular uncertainties of the adolescent passage, youth oscillates between taking life both, too seriously and easy. Searching for identity and integration, they tend to experiment with styles of behaviour and culturally defined patterns of lifestyles conductive to well-being. Sometimes, life is perceived as pure entertainment, and sometimes as pure drama. It's living theatre and theatre of life. On the one hand it is "acting out", on the other hand it is playing precisely defined roles. And, in-between, it is always the question: Who am I? They tend to slip into roles in order to check out whether they are willing to accept their implications with regard to the priorities they have set so far.

A Surface-Coupled Optical Trap with 1-bp Precision via Active Stabilization

PubMed Central

Okoniewski, Stephen R.; Carter, Ashley R.; Perkins, Thomas T.

2017-01-01

Optical traps can measure bead motions with Å-scale precision. However, using this level of precision to infer 1-bp motion of molecular motors along DNA is difficult, since a variety of noise sources degrade instrumental stability. In this chapter, we detail how to improve instrumental stability by (i) minimizing laser pointing, mode, polarization, and intensity noise using an acousto-optical-modulator mediated feedback loop and (ii) minimizing sample motion relative to the optical trap using a 3-axis piezo-electric-stage mediated feedback loop. These active techniques play a critical role in achieving a surface stability of 1 Å in 3D over tens of seconds and a 1-bp stability and precision in a surface-coupled optical trap over a broad bandwidth (Δf = 0.03–2 Hz) at low force (6 pN). These active stabilization techniques can also aid other biophysical assays that would benefit from improved laser stability and/or Å-scale sample stability, such as atomic force microscopy and super-resolution imaging. PMID:27844426

A Miniaturized On-Chip Colorimeter for Detecting NPK Elements

PubMed Central

Liu, Rui-Tao; Tao, Lu-Qi; Liu, Bo; Tian, Xiang-Guang; Mohammad, Mohammad Ali; Yang, Yi; Ren, Tian-Ling

2016-01-01

Recently, precision agriculture has become a globally attractive topic. As one of the most important factors, the soil nutrients play an important role in estimating the development of precision agriculture. Detecting the content of nitrogen, phosphorus and potassium (NPK) elements more efficiently is one of the key issues. In this paper, a novel chip-level colorimeter was fabricated to detect the NPK elements for the first time. A light source–microchannel photodetector in a sandwich structure was designed to realize on-chip detection. Compared with a commercial colorimeter, all key parts are based on MEMS (Micro-Electro-Mechanical System) technology so that the volume of this on-chip colorimeter can be minimized. Besides, less error and high precision are achieved. The cost of this colorimeter is two orders of magnitude less than that of a commercial one. All these advantages enable a low-cost and high-precision sensing operation in a monitoring network. The colorimeter developed herein has bright prospects for environmental and biological applications. PMID:27527177

A Miniaturized On-Chip Colorimeter for Detecting NPK Elements.

PubMed

Liu, Rui-Tao; Tao, Lu-Qi; Liu, Bo; Tian, Xiang-Guang; Mohammad, Mohammad Ali; Yang, Yi; Ren, Tian-Ling

2016-08-04

Recently, precision agriculture has become a globally attractive topic. As one of the most important factors, the soil nutrients play an important role in estimating the development of precision agriculture. Detecting the content of nitrogen, phosphorus and potassium (NPK) elements more efficiently is one of the key issues. In this paper, a novel chip-level colorimeter was fabricated to detect the NPK elements for the first time. A light source-microchannel photodetector in a sandwich structure was designed to realize on-chip detection. Compared with a commercial colorimeter, all key parts are based on MEMS (Micro-Electro-Mechanical System) technology so that the volume of this on-chip colorimeter can be minimized. Besides, less error and high precision are achieved. The cost of this colorimeter is two orders of magnitude less than that of a commercial one. All these advantages enable a low-cost and high-precision sensing operation in a monitoring network. The colorimeter developed herein has bright prospects for environmental and biological applications.

Improving the precision of the keyword-matching pornographic text filtering method using a hybrid model.

PubMed

Su, Gui-yang; Li, Jian-hua; Ma, Ying-hua; Li, Sheng-hong

2004-09-01

With the flooding of pornographic information on the Internet, how to keep people away from that offensive information is becoming one of the most important research areas in network information security. Some applications which can block or filter such information are used. Approaches in those systems can be roughly classified into two kinds: metadata based and content based. With the development of distributed technologies, content based filtering technologies will play a more and more important role in filtering systems. Keyword matching is a content based method used widely in harmful text filtering. Experiments to evaluate the recall and precision of the method showed that the precision of the method is not satisfactory, though the recall of the method is rather high. According to the results, a new pornographic text filtering model based on reconfirming is put forward. Experiments showed that the model is practical, has less loss of recall than the single keyword matching method, and has higher precision.

Superordinate Precision: An Examination of Academic Writing Among Bilingual Deaf and Hard of Hearing Students.

PubMed

Scott, Jessica A; Hoffmeister, Robert J

2018-04-01

Academic English is an essential literacy skill area for success in post-secondary education and in many work environments. Despite its importance, academic English is understudied with deaf and hard of hearing (DHH) students. Nascent research in this area suggests that academic English, alongside American Sign Language (ASL) fluency, may play an important role in the reading proficiency of DHH students in middle and high school. The current study expands this research to investigate academic English by examining student proficiency with a sub-skill of academic writing called superordinate precision, the taxonomical categorization of a term. Currently there is no research that examines DHH students' proficiency with superordinate precision. Middle and high school DHH students enrolled in bilingual schools for the deaf were assessed on their ASL proficiency, academic English proficiency, reading comprehension, and use of superordinate precision in definitions writing. Findings indicate that student use of superordinate precision in definitions writing was correlated with ASL proficiency, reading comprehension, and academic English proficiency. It is possible that degree of mastery of superordinate precision may indicate a higher overall level of proficiency with academic English. This may have important implications for assessment of and instruction in academic English literacy.

Signal recognition and parameter estimation of BPSK-LFM combined modulation

NASA Astrophysics Data System (ADS)

Long, Chao; Zhang, Lin; Liu, Yu

2015-07-01

Intra-pulse analysis plays an important role in electronic warfare. Intra-pulse feature abstraction focuses on primary parameters such as instantaneous frequency, modulation, and symbol rate. In this paper, automatic modulation recognition and feature extraction for combined BPSK-LFM modulation signals based on decision theoretic approach is studied. The simulation results show good recognition effect and high estimation precision, and the system is easy to be realized.

Receptive Fields and the Reconstruction of Visual Information.

DTIC Science & Technology

1985-09-01

depending on the noise . Thus our model would suggest that the interpolation filters for deblurring are playing a role in Ii hyperacuity. This is novel...of additional precision in the information can be obtained by a process of deblurring , which could be relevant to hyperacuity. It also provides an... impulse of heat diffuses into increasingly larger Gaussian distributions as time proceeds. Mathematically, let f(x) denote the initial temperature

[Immune system and tumors].

PubMed

Terme, Magali; Tanchot, Corinne

2017-02-01

Despite having been much debated, it is now well established that the immune system plays an essential role in the fight against cancer. In this article, we will highlight the implication of the immune system in the control of tumor growth and describe the major components of the immune system involved in the antitumoral immune response. The immune system, while exerting pressure on tumor cells, also will play a pro-tumoral role by sculpting the immunogenicity of tumors cells as they develop. Finally, we will illustrate the numerous mechanisms of immune suppression that take place within the tumoral microenvironment which allow tumor cells to escape control from the immune system. The increasingly precise knowledge of the brakes to an effective antitumor immune response allows the development of immunotherapy strategies more and more innovating and promising of hope. Copyright © 2016. Published by Elsevier Masson SAS.

Density functional study of molecular interactions in secondary structures of proteins.

PubMed

Takano, Yu; Kusaka, Ayumi; Nakamura, Haruki

2016-01-01

Proteins play diverse and vital roles in biology, which are dominated by their three-dimensional structures. The three-dimensional structure of a protein determines its functions and chemical properties. Protein secondary structures, including α-helices and β-sheets, are key components of the protein architecture. Molecular interactions, in particular hydrogen bonds, play significant roles in the formation of protein secondary structures. Precise and quantitative estimations of these interactions are required to understand the principles underlying the formation of three-dimensional protein structures. In the present study, we have investigated the molecular interactions in α-helices and β-sheets, using ab initio wave function-based methods, the Hartree-Fock method (HF) and the second-order Møller-Plesset perturbation theory (MP2), density functional theory, and molecular mechanics. The characteristic interactions essential for forming the secondary structures are discussed quantitatively.

Dynamics modeling for sugar cane sucrose estimation using time series satellite imagery

NASA Astrophysics Data System (ADS)

Zhao, Yu; Justina, Diego Della; Kazama, Yoriko; Rocha, Jansle Vieira; Graziano, Paulo Sergio; Lamparelli, Rubens Augusto Camargo

2016-10-01

Sugarcane, as one of the most mainstay crop in Brazil, plays an essential role in ethanol production. To monitor sugarcane crop growth and predict sugarcane sucrose content, remote sensing technology plays an essential role while accurate and timely crop growth information is significant, in particularly for large scale farming. We focused on the issues of sugarcane sucrose content estimation using time-series satellite image. Firstly, we calculated the spectral features and vegetation indices to make them be correspondence to the sucrose accumulation biological mechanism. Secondly, we improved the statistical regression model considering more other factors. The evaluation was performed and we got precision of 90% which is about 20% higher than the conventional method. The validation results showed that prediction accuracy using our sugarcane growth modeling and improved mix model is satisfied.

Phosphorylation of paramyxovirus phosphoprotein and its role in viral gene expression.

PubMed

Fuentes, Sandra M; Sun, Dengyun; Schmitt, Anthony P; He, Biao

2010-01-01

Paramyxoviruses include many important human and animal pathogens such as measles virus, mumps virus, human parainfluenza viruses, and respiratory syncytial virus, as well as emerging viruses such as Nipah virus and Hendra virus. The paramyxovirus RNA-dependent RNA polymerase consists of the phosphoprotein (P) and the large protein. Both of these proteins are essential for viral RNA synthesis. The P protein is phosphorylated at multiple sites, probably by more than one host kinase. While it is thought that the phosphorylation of P is important for its role in viral RNA synthesis, the precise role of P protein phosphorylation remains an enigma. For instance, it was demonstrated that the putative CKII phosphorylation sites of the P protein of respiratory syncytial virus play a role in viral RNA synthesis using a minigenome replicon system; however, mutating these putative CKII phosphorylation sites within a viral genome had no effect on viral RNA synthesis, leading to the hypothesis that P protein phosphorylation, at least by CKII, does not play a role in viral RNA synthesis. Recently, it has been reported that the phosphorylation state of the P protein of parainfluenza virus 5, a prototypical paramyxovirus, correlates with the ability of P protein to synthesize viral RNA, indicating that P protein phosphorylation does in fact play a role in viral RNA synthesis. Furthermore, host kinases PLK1, as well as AKT1 have been found to play critical roles in paramyxovirus RNA synthesis through regulation of P protein phosphorylation status. Beyond furthering our understanding of paramyxovirus RNA replication, these recent discoveries may also result in a new paradigm in treating infections caused by these viruses, as host kinases that regulate paramyxovirus replication are investigated as potential targets of therapeutic intervention.

TOPBP1Dpb11 plays a conserved role in homologous recombination DNA repair through the coordinated recruitment of 53BP1Rad9

PubMed Central

Sims, Jennie Rae; Freire, Raimundo

2017-01-01

Genome maintenance and cancer suppression require homologous recombination (HR) DNA repair. In yeast and mammals, the scaffold protein TOPBP1Dpb11 has been implicated in HR, although its precise function and mechanism of action remain elusive. In this study, we show that yeast Dpb11 plays an antagonistic role in recombination control through regulated protein interactions. Dpb11 mediates opposing roles in DNA end resection by coordinating both the stabilization and exclusion of Rad9 from DNA lesions. The Mec1 kinase promotes the pro-resection function of Dpb11 by mediating its interaction with the Slx4 scaffold. Human TOPBP1Dpb11 engages in interactions with the anti-resection factor 53BP1 and the pro-resection factor BRCA1, suggesting that TOPBP1 also mediates opposing functions in HR control. Hyperstabilization of the 53BP1–TOPBP1 interaction enhances the recruitment of 53BP1 to nuclear foci in the S phase, resulting in impaired HR and the accumulation of chromosomal aberrations. Our results support a model in which TOPBP1Dpb11 plays a conserved role in mediating a phosphoregulated circuitry for the control of recombinational DNA repair. PMID:28228534

Regulation of cellular plasticity and resilience by mood stabilizers: the role of AMPA receptor trafficking

PubMed Central

Du, Jing; Quiroz, Jorge A.; Gray, Neil A.; Szabo, Steve T.; Zarate Jr, Carlos A.; Manji, Husseini K.

2004-01-01

There is increasing evidence from a variety of sources that severe mood disorders are associated with regional reductions in brain volume, as well as reductions in the number, size, and density of glia and neurons in discrete brain areas. Although the precise pathophysiology underlying these morphometric changes remains to be fully elucidated, the data suggest that severe mood disorders are associated with impairments of structural plasticity and cellular resilience. In this context, it is noteworthy that a growing body of data suggests that the glutamaiergic system (which is known to play a major role in neuronal plasticity and cellular resilience) may be involved in the pathophysiology and treatment of mood disorders. Glutamate α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) GluR1 receptor trafficking plays a critical role in regulating various forms of neural plasticity. It is thus noteworthy that recent studies have shown that structurally dissimilar mood stabilizers lithium and valproate regulate GluR1 receptor subunit trafficking and localization at synapses. These studies suggest that regulation of glutamatergically mediated synaptic plasticity may play a role in the treatment of mood disorders, and raises the possibility that agents more directly affecting synaptic GluR1 represent novel therapies for these devastating illnesses. PMID:22034247

Precise through-space control of an abiotic electrophilic aromatic substitution reaction

NASA Astrophysics Data System (ADS)

Murphy, Kyle E.; Bocanegra, Jessica L.; Liu, Xiaoxi; Chau, H.-Y. Katharine; Lee, Patrick C.; Li, Jianing; Schneebeli, Severin T.

2017-04-01

Nature has evolved selective enzymes for the efficient biosynthesis of complex products. This exceptional ability stems from adapted enzymatic pockets, which geometrically constrain reactants and stabilize specific reactive intermediates by placing electron-donating/accepting residues nearby. Here we perform an abiotic electrophilic aromatic substitution reaction, which is directed precisely through space. Ester arms--positioned above the planes of aromatic rings--enable it to distinguish between nearly identical, neighbouring reactive positions. Quantum mechanical calculations show that, in two competing reaction pathways, both [C-H...O]-hydrogen bonding and electrophile preorganization by coordination to a carbonyl group likely play a role in controlling the reaction. These through-space-directed mechanisms are inspired by dimethylallyl tryptophan synthases, which direct biological electrophilic aromatic substitutions by preorganizing dimethylallyl cations and by stabilizing reactive intermediates with [C-H...N]-hydrogen bonding. Our results demonstrate how the third dimension above and underneath aromatic rings can be exploited to precisely control electrophilic aromatic substitutions.

Looking sharp: Becoming a search template boosts precision and stability in visual working memory.

PubMed

Rajsic, Jason; Ouslis, Natasha E; Wilson, Daryl E; Pratt, Jay

2017-08-01

Visual working memory (VWM) plays a central role in visual cognition, and current work suggests that there is a special state in VWM for items that are the goal of visual searches. However, whether the quality of memory for target templates differs from memory for other items in VWM is currently unknown. In this study, we measured the precision and stability of memory for search templates and accessory items to determine whether search templates receive representational priority in VWM. Memory for search templates exhibited increased precision and probability of recall, whereas accessory items were remembered less often. Additionally, while memory for Templates showed benefits when instances of the Template appeared in search, this benefit was not consistently observed for Accessory items when they appeared in search. Our results show that becoming a search template can substantially affect the quality of a representation in VWM.

Planowanie strategiczne kluczowym czynnikiem rozwoju turystyki w regionie

NASA Astrophysics Data System (ADS)

Majewska, Iwona

2009-01-01

Elaborating strategic documents is being perceived as a basis for different initiatives and projects which on the other side stimulate regional and local development in various spheres. Tourism economy is one of the most efficient factor of the local and regional development thanks to its intersector links. It must be also stressed that the tourism economy will have the biggest influence on regional development the less nowadays the tourism potential is being explored. In such situation elaborating professional strategic documents like businessplans, tourism development strategies, tourism product development programmers, feasibility studies plays a key role. Documents containing clear action plans, being a scenario for the next years allow to avoid "ad hoc" actions and at the same time making mistakes that are sometimes very costly. Precisely identified and selected set of objectives and aims allows to concentrate resources on the most important, and, what is crucial, socially accepted actions. In tourism acceptance plays a key role because the whole community participates in tourism development and in image creation that influences directly on attractiveness, number of visitors and economic and social benefits. This is why the strategic planning plays a crucial role in the context of regional and local development.

Hepatic JAK2 protects against atherosclerosis through circulating IGF-1

PubMed Central

Sivasubramaniyam, Tharini; Schroer, Stephanie A.; Li, Angela; Luk, Cynthia T.; Shi, Sally Yu; Besla, Rickvinder; Metherel, Adam H.; Kitson, Alex P.; Brunt, Jara J.; Lopes, Joshua; Wagner, Kay-Uwe; Bazinet, Richard P.; Bendeck, Michelle P.; Robbins, Clinton S.

2017-01-01

Atherosclerosis is considered both a metabolic and inflammatory disease; however, the specific tissue and signaling molecules that instigate and propagate this disease remain unclear. The liver is a central site of inflammation and lipid metabolism that is critical for atherosclerosis, and JAK2 is a key mediator of inflammation and, more recently, of hepatic lipid metabolism. However, precise effects of hepatic Jak2 on atherosclerosis remain unknown. We show here that hepatic Jak2 deficiency in atherosclerosis-prone mouse models exhibited accelerated atherosclerosis with increased plaque macrophages and decreased plaque smooth muscle cell content. JAK2’s essential role in growth hormone signalling in liver that resulted in reduced IGF-1 with hepatic Jak2 deficiency played a causal role in exacerbating atherosclerosis. As such, restoring IGF-1 either pharmacologically or genetically attenuated atherosclerotic burden. Together, our data show hepatic Jak2 to play a protective role in atherogenesis through actions mediated by circulating IGF-1 and, to our knowledge, provide a novel liver-centric mechanism in atheroprotection. PMID:28724798

Statistical inference to advance network models in epidemiology.

PubMed

Welch, David; Bansal, Shweta; Hunter, David R

2011-03-01

Contact networks are playing an increasingly important role in the study of epidemiology. Most of the existing work in this area has focused on considering the effect of underlying network structure on epidemic dynamics by using tools from probability theory and computer simulation. This work has provided much insight on the role that heterogeneity in host contact patterns plays on infectious disease dynamics. Despite the important understanding afforded by the probability and simulation paradigm, this approach does not directly address important questions about the structure of contact networks such as what is the best network model for a particular mode of disease transmission, how parameter values of a given model should be estimated, or how precisely the data allow us to estimate these parameter values. We argue that these questions are best answered within a statistical framework and discuss the role of statistical inference in estimating contact networks from epidemiological data. Copyright © 2011 Elsevier B.V. All rights reserved.

Specialized Representations of Value in the Orbital and Ventrolateral Prefrontal Cortex: Desirability versus Availability of Outcomes.

PubMed

Rudebeck, Peter H; Saunders, Richard C; Lundgren, Dawn A; Murray, Elisabeth A

2017-08-30

Advantageous foraging choices benefit from an estimation of two aspects of a resource's value: its current desirability and availability. Both orbitofrontal and ventrolateral prefrontal areas contribute to updating these valuations, but their precise roles remain unclear. To explore their specializations, we trained macaque monkeys on two tasks: one required updating representations of a predicted outcome's desirability, as adjusted by selective satiation, and the other required updating representations of an outcome's availability, as indexed by its probability. We evaluated performance on both tasks in three groups of monkeys: unoperated controls and those with selective, fiber-sparing lesions of either the OFC or VLPFC. Representations that depend on the VLPFC but not the OFC play a necessary role in choices based on outcome availability; in contrast, representations that depend on the OFC but not the VLPFC play a necessary role in choices based on outcome desirability. Copyright © 2017 Elsevier Inc. All rights reserved.

A Critical Role for Ubiquitination in the Endocytosis of Glutamate Receptors.

PubMed

Gulia, Ravinder; Sharma, Rohan; Bhattacharyya, Samarjit

2017-01-27

Group I metabotropic glutamate receptors (mGluRs) play important roles in various neuronal processes and elicit changes in synaptic efficacy through AMPA receptor (AMPAR) endocytosis. Trafficking of mGluRs plays an important role in controlling the precise localization of these receptors at specific region of the cell; it also regulates the activity of these receptors. Despite this obvious significance, we know very little about the cellular mechanisms that control the trafficking of group I mGluRs. We show here that ligand-mediated internalization of group I mGluRs is ubiquitination-dependent. A lysine residue (Lys 1112 ) at the C-terminal tail of mGluR1 (a member of the group I mGluR family) plays crucial role in this process. Our data suggest that Lys 63 -linked polyubiquitination is involved in the ligand-mediated endocytosis of mGluR1. We also show here that the mGluR1 internalization is dependent on a specific E3 ubiquitin ligase, Siah-1A. Furthermore, acute knockdown of Siah-1A enhances the mGluR-mediated AMPAR endocytosis. These studies reveal a novel function of ubiquitination in the regulation of group I mGluRs, as well as its role in mGluR-dependent AMPAR endocytosis. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

[Neurohumoral mechanisms for vasovagal syncopes. Part II].

PubMed

Gajek, Jacek; Zyśko, Dorota

2003-04-01

Vasovagal syncope is defined as a reflex loss of consciousness related to reaction to various stimuli as orthostatic stress, pain or emotions connected with loss of muscle postural tone. In the second part of the paper the authors describe the possible role of the particular neurohumoral factors and autonomic nervous system in the development of vasovagal syncope. The studies on the involvement of neurohumoral factors in vasovagal syncope can play a key role in a more precise evaluation of affected patients, long term prophylaxis against syncopal events and may contribute to development of more reliable diagnostic tests.

Information Retrieval on social network: An Adaptive Proof

NASA Astrophysics Data System (ADS)

Elveny, M.; Syah, R.; Elfida, M.; Nasution, M. K. M.

2018-01-01

Information Retrieval has become one of the areas for studying to get the trusty information, with which the recall and precision become the measurement form that represents it. Nevertheless, development in certain scientific fields make it possible to improve the performance of the Information Retrieval. In this case, through social networks whereby the role of social actor degrees plays a role. This is an implication of the query in which co-occurrence becomes an indication of social networks. An adaptive approach we use by involving this query in sequence to a stand-alone query, it has proven the relationship among them.

Application of Multimodality Imaging Fusion Technology in Diagnosis and Treatment of Malignant Tumors under the Precision Medicine Plan.

PubMed

Wang, Shun-Yi; Chen, Xian-Xia; Li, Yi; Zhang, Yu-Ying

2016-12-20

The arrival of precision medicine plan brings new opportunities and challenges for patients undergoing precision diagnosis and treatment of malignant tumors. With the development of medical imaging, information on different modality imaging can be integrated and comprehensively analyzed by imaging fusion system. This review aimed to update the application of multimodality imaging fusion technology in the precise diagnosis and treatment of malignant tumors under the precision medicine plan. We introduced several multimodality imaging fusion technologies and their application to the diagnosis and treatment of malignant tumors in clinical practice. The data cited in this review were obtained mainly from the PubMed database from 1996 to 2016, using the keywords of "precision medicine", "fusion imaging", "multimodality", and "tumor diagnosis and treatment". Original articles, clinical practice, reviews, and other relevant literatures published in English were reviewed. Papers focusing on precision medicine, fusion imaging, multimodality, and tumor diagnosis and treatment were selected. Duplicated papers were excluded. Multimodality imaging fusion technology plays an important role in tumor diagnosis and treatment under the precision medicine plan, such as accurate location, qualitative diagnosis, tumor staging, treatment plan design, and real-time intraoperative monitoring. Multimodality imaging fusion systems could provide more imaging information of tumors from different dimensions and angles, thereby offing strong technical support for the implementation of precision oncology. Under the precision medicine plan, personalized treatment of tumors is a distinct possibility. We believe that multimodality imaging fusion technology will find an increasingly wide application in clinical practice.

The Dopaminergic Midbrain Encodes the Expected Certainty about Desired Outcomes.

PubMed

Schwartenbeck, Philipp; FitzGerald, Thomas H B; Mathys, Christoph; Dolan, Ray; Friston, Karl

2015-10-01

Dopamine plays a key role in learning; however, its exact function in decision making and choice remains unclear. Recently, we proposed a generic model based on active (Bayesian) inference wherein dopamine encodes the precision of beliefs about optimal policies. Put simply, dopamine discharges reflect the confidence that a chosen policy will lead to desired outcomes. We designed a novel task to test this hypothesis, where subjects played a "limited offer" game in a functional magnetic resonance imaging experiment. Subjects had to decide how long to wait for a high offer before accepting a low offer, with the risk of losing everything if they waited too long. Bayesian model comparison showed that behavior strongly supported active inference, based on surprise minimization, over classical utility maximization schemes. Furthermore, midbrain activity, encompassing dopamine projection neurons, was accurately predicted by trial-by-trial variations in model-based estimates of precision. Our findings demonstrate that human subjects infer both optimal policies and the precision of those inferences, and thus support the notion that humans perform hierarchical probabilistic Bayesian inference. In other words, subjects have to infer both what they should do as well as how confident they are in their choices, where confidence may be encoded by dopaminergic firing. © The Author 2014. Published by Oxford University Press.

The Dopaminergic Midbrain Encodes the Expected Certainty about Desired Outcomes

PubMed Central

Schwartenbeck, Philipp; FitzGerald, Thomas H. B.; Mathys, Christoph; Dolan, Ray; Friston, Karl

2015-01-01

Dopamine plays a key role in learning; however, its exact function in decision making and choice remains unclear. Recently, we proposed a generic model based on active (Bayesian) inference wherein dopamine encodes the precision of beliefs about optimal policies. Put simply, dopamine discharges reflect the confidence that a chosen policy will lead to desired outcomes. We designed a novel task to test this hypothesis, where subjects played a “limited offer” game in a functional magnetic resonance imaging experiment. Subjects had to decide how long to wait for a high offer before accepting a low offer, with the risk of losing everything if they waited too long. Bayesian model comparison showed that behavior strongly supported active inference, based on surprise minimization, over classical utility maximization schemes. Furthermore, midbrain activity, encompassing dopamine projection neurons, was accurately predicted by trial-by-trial variations in model-based estimates of precision. Our findings demonstrate that human subjects infer both optimal policies and the precision of those inferences, and thus support the notion that humans perform hierarchical probabilistic Bayesian inference. In other words, subjects have to infer both what they should do as well as how confident they are in their choices, where confidence may be encoded by dopaminergic firing. PMID:25056572

The role of informatics in patient-centered care and personalized medicine.

PubMed

Hanna, Matthew G; Pantanowitz, Liron

2017-06-01

The practice of cytopathology has dramatically changed due to advances in genomics and information technology. Cytology laboratories have accordingly become increasingly dependent on pathology informatics support to meet the emerging demands of precision medicine. Pathology informatics deals with information technology in the laboratory, and the impact of this technology on workflow processes and staff who interact with these tools. This article covers the critical role that laboratory information systems, electronic medical records, and digital imaging plays in patient-centered personalized medicine. The value of integrated diagnostic reports, clinical decision support, and the use of whole-slide imaging to better evaluate cytology samples destined for molecular testing is discussed. Image analysis that offers more precise and quantitative measurements in cytology is addressed, as well as the role of bioinformatics tools to cope with Big Data from next-generation sequencing. This article also highlights the barriers to the widespread adoption of these disruptive technologies due to regulatory obstacles, limited commercial solutions, poor interoperability, and lack of standardization. Cancer Cytopathol 2017;125(6 suppl):494-501. © 2017 American Cancer Society. © 2017 American Cancer Society.

Precision or Personalized Medicine for Cancer Chemotherapy: Is there a Role for Herbal Medicine.

PubMed

Wang, Zhijun; Liu, Xuefeng; Ho, Rebecca Lucinda Ka Yan; Lam, Christopher Wai Kei; Chow, Moses Sing Sum

2016-07-07

Although over 100 chemotherapeutic agents are currently available for the treatment of cancer patients, the overall long term clinical benefit is disappointing due to the lack of effectiveness or severe side effects from these agents. In order to improve the therapeutic outcome, a new approach called precision medicine or personalized medicine has been proposed and initiated by the U.S. National Institutes of Health. However, the limited availability of effective medications and the high cost are still the major barriers for many cancer patients. Thus alternative approaches such as herbal medicines could be a feasible and less costly option. Unfortunately, scientific evidence for the efficacy of a majority of herbal medicines is still lacking and their development to meet FDA approval or other regulatory agencies is a big challenge. However, herbal medicines may be able to play an important role in precision medicine or personalized medicine. This review will focus on the existing and future technologies that could speed the development of herbal products for treatment of resistant cancer in individual patients. Specifically, it will concentrate on reviewing the phenotypic (activity based) rather than genotypic (mechanism based) approach to develop herbal medicine useful for personalized cancer chemotherapy.

Impulsive Effects on Quasi-Synchronization of Neural Networks With Parameter Mismatches and Time-Varying Delay.

PubMed

Tang, Ze; Park, Ju H; Feng, Jianwen

2018-04-01

This paper is concerned with the exponential synchronization issue of nonidentically coupled neural networks with time-varying delay. Due to the parameter mismatch phenomena existed in neural networks, the problem of quasi-synchronization is thus discussed by applying some impulsive control strategies. Based on the definition of average impulsive interval and the extended comparison principle for impulsive systems, some criteria for achieving the quasi-synchronization of neural networks are derived. More extensive ranges of impulsive effects are discussed so that impulse could either play an effective role or play an adverse role in the final network synchronization. In addition, according to the extended formula for the variation of parameters with time-varying delay, precisely exponential convergence rates and quasi-synchronization errors are obtained, respectively, in view of different types impulsive effects. Finally, some numerical simulations with different types of impulsive effects are presented to illustrate the effectiveness of theoretical analysis.

Glucagon-like peptide-1 and cholecystokinin production and signaling in the pancreatic islet as an adaptive response to obesity.

PubMed

Linnemann, Amelia K; Davis, Dawn Belt

2016-04-01

Precise control of blood glucose is dependent on adequate β-cell mass and function. Thus, reductions in β-cell mass and function lead to insufficient insulin production to meet demand, and result in diabetes. Recent evidence suggests that paracrine signaling in the islet might be important in obesity, and disruption of this signaling could play a role in the pathogenesis of diabetes. For example, we recently discovered a novel islet incretin axis where glucagon-like peptide-1 regulates β-cell production of another classic gut hormone, cholecystokinin. This axis is stimulated by obesity, and plays a role in enhancing β-cell survival. In the present review, we place our observations in the wider context of the literature on incretin regulation in the islet, and discuss the potential for therapeutic targeting of these pathways.

[Cor triatriatum. Anatomical forms and surgical treatment of 6 consecutive cases].

PubMed

Bloch, G; Heurtematte, Y; Menu, P; Mesnildrey, P; Casasoprana, A; Magnier, S; Tamari, W; Seurat, M C; Aubry, P; Vernant, P

1988-01-01

Six cases of cor triatriatum documented and operated on at Henri-Mondor hospital between 1980 and 1984 are reported. Ages at the time of surgery ranged from 8 months to 57 years. Four of the 6 patients presented with pulmonary hypertension. Anatomic types consisted of 4 diaphragmatic types and 2 more complex malformations. Associated lesions were present in all but one patients. They consisted mostly of interatrial defects (depending on their position with regard to the intra-atrial membrane, they play a determinant role in the symptomatology) and of a left superior vena cava (which might play a role in the embryogenesis of the malformation). Except for one early postoperative death, results of surgery were excellent for all patients, with a mean follow-up of 5 years. This series, compared with the literature, allows precising the embryologic and anatomic aspects of the malformation and the surgical techniques in complex types.

Mitochondria and cancer: a growing role in apoptosis, cancer cell metabolism and dedifferentiation.

PubMed

Scatena, Roberto

2012-01-01

At the beginning of the twentieth century, Otto Warburg demonstrated that cancer cells have a peculiar metabolism. These cells preferentially utilise glycolysis for energetic and anabolic purposes, producing large quantities of lactic acid. He defined this unusual metabolism "aerobic glycolysis". At the same time, Warburg hypothesised that a disruption of mitochondrial activities played a precise pathogenic role in cancer. Because of this so-called "Warburg effect", mitochondrial physiology and cellular respiration in particular have been overlooked in pathophysiological studies of cancer. Over time, however, many studies have shown that mitochondria play a fundamental role in cell death by apoptosis or necrosis. Moreover, metabolic enzymes of the Krebs cycle have also recently been recognised as oncosuppressors. Recently, a series of studies were undertaken to re-evaluate the role of oxidative mitochondrial metabolism in cancer cell growth and progression. Some of these data indicate that modulation of mitochondrial respiration may induce an arrest of cancer cell proliferation and differentiation (pseudodifferentiation) and/or or death, suggesting that iatrogenic manipulation of some mitochondrial activities may induce anticancer effects. Moreover, studying the role of mitochondria in cancer cell dedifferentiation/differentiation processes may allow further insight into the pathophysiology and therapy of so-called cancer stem cells.

Research on key technology of the verification system of steel rule based on vision measurement

NASA Astrophysics Data System (ADS)

Jia, Siyuan; Wang, Zhong; Liu, Changjie; Fu, Luhua; Li, Yiming; Lu, Ruijun

2018-01-01

The steel rule plays an important role in quantity transmission. However, the traditional verification method of steel rule based on manual operation and reading brings about low precision and low efficiency. A machine vison based verification system of steel rule is designed referring to JJG1-1999-Verificaiton Regulation of Steel Rule [1]. What differentiates this system is that it uses a new calibration method of pixel equivalent and decontaminates the surface of steel rule. Experiments show that these two methods fully meet the requirements of the verification system. Measuring results strongly prove that these methods not only meet the precision of verification regulation, but also improve the reliability and efficiency of the verification system.

Eigenfunction Expansions and Lippmann-Schwinger Formulas

NASA Astrophysics Data System (ADS)

Gadella, M.; Kielanowski, P.

2011-12-01

In this paper we discuss in the mathematically precise way the definition of a resonance, that requires two Hamiltonians (free and perturbed), the notion of Gamow vectors, Lippmann-Schwinger equations and the analytic properties of their solutions in the context of the Gamow vectors. Next we discuss the eigenfunction expansions in the presence of resonances. In the case of the Friedrichs model, the precise form of these generalized eigenfunctions has been given in the literature. Although there are two families of eigenfunction expansions which are related through the time reversal operator, free and perturbed Hamiltonians are time invariant. On the other hand, PT symmetries play no role in this discussion. Our discussion clarifies the results of the paper [1], which contains imprecise or even wrong statements.

NASA Webb Mirror is 'CIAF' and Sound

NASA Image and Video Library

2017-12-08

A James Webb Space Telescope flight spare primary mirror segment is loaded onto the CMM (Configuration Measurement Machine) at the CIAF (Calibration, Integration and Alignment Facility) at NASA's Goddard Space Flight Center in Greenbelt, Md. The CMM is used for precision measurements of the mirrors. These precision measurements must be accurate to 0.1 microns or 1/400th the thickness of a human hair. Image credit: NASA/Goddard/Chris Gunn NASA image use policy. NASA Goddard Space Flight Center enables NASA’s mission through four scientific endeavors: Earth Science, Heliophysics, Solar System Exploration, and Astrophysics. Goddard plays a leading role in NASA’s accomplishments by contributing compelling scientific knowledge to advance the Agency’s mission. Follow us on Twitter Like us on Facebook Find us on Instagram

Accuracy and precision evaluation of seven self-monitoring blood glucose systems.

PubMed

Kuo, Chih-Yi; Hsu, Cheng-Teng; Ho, Cheng-Shiao; Su, Ting-En; Wu, Ming-Hsun; Wang, Chau-Jong

2011-05-01

Self-monitoring blood glucose (SMBG) systems play a critical role in management of diabetes. SMBG systems should at least meet the minimal requirement of the World Health Organization's ISO 15197:2003. For tight glycemic control, a tighter accuracy requirement is needed. Seven SMBG systems were evaluated for accuracy and precision: Bionime Rightest(™) GM550 (Bionime Corp., Dali City, Taiwan), Accu-Chek(®) Performa (Roche Diagnostics, Indianapolis, IN), OneTouch(®) Ultra(®)2 (LifeScan Inc., Milpitas, CA), MediSense(®) Optium(™) Xceed (Abbott Diabetes Care Inc., Alameda, CA), Medisafe (TERUMO Corp., Tokyo, Japan), Fora(®) TD4227 (Taidac Technology Corp., Wugu Township, Taiwan), and Ascensia Contour(®) (Bayer HealthCare LLC, Mishawaka, IN). The 107 participants (44 men and 63 women) were between 23 and 91 years old. The analytical results of seven SMBG systems were compared with those of plasma analyzed with the hexokinase method (Olympus AU640, Olympus America Inc., Center Valley, PA). The imprecision of the seven blood glucose meters ranged from 1.1% to 4.7%. Three of the seven blood glucose meters (42.9%) fulfilled the minimum accuracy criteria of ISO 15197:2003. The mean absolute relative error value for each blood glucose meter was calculated and ranged from 6.5% to 12.0%. More than 40% of evaluated SMBG systems meet the minimal accuracy criteria requirement of ISO 15197:2003. However, considering tighter criteria for accuracy of ±15%, only the Bionime Rightest GM550 meets this requirement. Because SMBG systems play a critical role in management of diabetes, manufacturers have to strive to improve accuracy and precision and to ensure the good quality of blood glucose meters and test strips.

Second Iteration of Photogrammetric Pipeline to Enhance the Accuracy of Image Pose Estimation

NASA Astrophysics Data System (ADS)

Nguyen, T. G.; Pierrot-Deseilligny, M.; Muller, J.-M.; Thom, C.

2017-05-01

In classical photogrammetric processing pipeline, the automatic tie point extraction plays a key role in the quality of achieved results. The image tie points are crucial to pose estimation and have a significant influence on the precision of calculated orientation parameters. Therefore, both relative and absolute orientations of the 3D model can be affected. By improving the precision of image tie point measurement, one can enhance the quality of image orientation. The quality of image tie points is under the influence of several factors such as the multiplicity, the measurement precision and the distribution in 2D images as well as in 3D scenes. In complex acquisition scenarios such as indoor applications and oblique aerial images, tie point extraction is limited while only image information can be exploited. Hence, we propose here a method which improves the precision of pose estimation in complex scenarios by adding a second iteration to the classical processing pipeline. The result of a first iteration is used as a priori information to guide the extraction of new tie points with better quality. Evaluated with multiple case studies, the proposed method shows its validity and its high potiential for precision improvement.

Expression patterns of genes encoding plasma membrane aquaporins during fruit development in cucumber (Cucumis sativus L.).

PubMed

Shi, Jin; Wang, Jinfang; Li, Ren; Li, Dianbo; Xu, Fengfeng; Sun, Qianqian; Zhao, Bin; Mao, Ai-Jun; Guo, Yang-Dong

2015-11-01

Aquaporins are membrane channels precisely regulating water movement through cell membranes in most living organisms. Despite the advances in the physiology of fruit development, their participation during fruit development in cucumber still barely understood. In this paper, the expressions of 12 genes encoding plasma membrane intrinsic proteins (PIPs) were analyzed during cucumber fruit development in our work. Based on the homology search with known PIPs from rice, Arabidopsis and strawberry, 12 cucumber PIP genes subfamily members were identified. Cellular localization assays indicated that CsPIPs were localized in the plasma membrane. The qRT-PCR analysis of CsPIPs showed that 12 CsPIPs were differentially expressed during fruit development. These results suggest that 12 genes encoding plasma membrane intrinsic proteins (CsPIPs) play very important roles in cucumber life cycle and the data generated will be helpful in understanding their precise roles during fruit development in cucumber. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Some aspects of precise laser machining - Part 2: Experimental

NASA Astrophysics Data System (ADS)

Grabowski, Marcin; Wyszynski, Dominik; Ostrowski, Robert

2018-05-01

The paper describes the role of laser beam polarization on quality of laser beam machined cutting tool edge. In micromachining the preparation of the cutting tools in play a key role on dimensional accuracy, sharpness and the quality of the cutting edges. In order to assure quality and dimensional accuracy of the cutting tool edge it is necessary to apply laser polarization control. In the research diode pumped Nd:YAG 532nm pulse laser was applied. Laser beam polarization used in the research was linear (horizontal, vertical). The goal of the carried out research was to describe impact of laser beam polarization on efficiency of the cutting process and quality of machined parts (edge, surface) made of polycrystalline diamond (PCD) and cubic boron nitride (cBN). Application of precise cutting tool in micromachining has significant impact on the minimum uncut chip thickness and quality of the parts. The research was carried within the INNOLOT program funded by the National Centre for Research and Development.

A Surface-Coupled Optical Trap with 1-bp Precision via Active Stabilization.

PubMed

Okoniewski, Stephen R; Carter, Ashley R; Perkins, Thomas T

2017-01-01

Optical traps can measure bead motions with Å-scale precision. However, using this level of precision to infer 1-bp motion of molecular motors along DNA is difficult, since a variety of noise sources degrade instrumental stability. In this chapter, we detail how to improve instrumental stability by (1) minimizing laser pointing, mode, polarization, and intensity noise using an acousto-optical-modulator mediated feedback loop and (2) minimizing sample motion relative to the optical trap using a three-axis piezo-electric-stage mediated feedback loop. These active techniques play a critical role in achieving a surface stability of 1 Å in 3D over tens of seconds and a 1-bp stability and precision in a surface-coupled optical trap over a broad bandwidth (Δf = 0.03-2 Hz) at low force (6 pN). These active stabilization techniques can also aid other biophysical assays that would benefit from improved laser stability and/or Å-scale sample stability, such as atomic force microscopy and super-resolution imaging.

The Magsat magnetometer boom

NASA Technical Reports Server (NTRS)

Smola, J. F.; Radford, W. E.; Reitz, M. H.

1980-01-01

A lightweight extendable structure that can precisely position magnetically sensitive instruments safe distances from magnetic sources in a spacecraft is described as well as the major areas of concern that played dominant roles in its development. Weight, packaging volume, thermal distortion, mechanical misalignments, dimensional instability, launch environments, and low temperature functioning were areas that presented some formidable obstacles. The ways in which these obstacles were dealt with are examined for those involving the development of similar aerospace mechanisms with equally restrictive requirements.

Cyclin-dependent kinases: engines, clocks, and microprocessors.

PubMed

Morgan, D O

1997-01-01

Cyclin-dependent kinases (Cdks) play a well-established role in the regulation of the eukaryotic cell division cycle and have also been implicated in the control of gene transcription and other processes. Cdk activity is governed by a complex network of regulatory subunits and phosphorylation events whose precise effects on Cdk conformation have been revealed by recent crystallographic studies. In the cell, these regulatory mechanisms generate an interlinked series of Cdk oscillators that trigger the events of cell division.

ACCURATE ORBITAL INTEGRATION OF THE GENERAL THREE-BODY PROBLEM BASED ON THE D'ALEMBERT-TYPE SCHEME

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

Minesaki, Yukitaka

2013-03-15

We propose an accurate orbital integration scheme for the general three-body problem that retains all conserved quantities except angular momentum. The scheme is provided by an extension of the d'Alembert-type scheme for constrained autonomous Hamiltonian systems. Although the proposed scheme is merely second-order accurate, it can precisely reproduce some periodic, quasiperiodic, and escape orbits. The Levi-Civita transformation plays a role in designing the scheme.

Promoter Melting Plays Critical Role in Lymphocyte Activation | Center for Cancer Research

Cancer.gov

Transcription in eukaryotic cells is a precisely timed ballet that consists of RNA polymerase II (pol II) recruitment to gene promoters, assembly of the multiprotein preinitiation complex, opening of the DNA, escape of pol II from the promoter, pol II pausing downstream, mRNA elongation, and, eventually, termination. The two main points of regulation are thought to be polymerase recruitment and pause release, but most studies investigating these regulatory processes involved actively cycling cells.

Rho-guanine nucleotide exchange factors during development

PubMed Central

Mulinari, Shai

2010-01-01

The development of multicellular organisms is associated with extensive rearrangements of tissues and cell sheets. The driving force for these rearrangements is generated mostly by the actin cytoskeleton. In order to permit the reproducible development of a specific body plan, dynamic reorganization of the actin cytoskeleton must be precisely coordinated in space and time. GTP-exchange factors that activate small GTPases of the Rho family play an important role in this process. Here we review the role of this class of cytoskeletal regulators during important developmental processes such as epithelial morphogenesis, cytokinesis, cell migration, cell polarity, neuronal growth cone extension and phagocytosis in different model systems. PMID:21686118

Spliced XBP1 promotes macrophage survival and autophagy by interacting with Beclin-1

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

Tian, Ping-Ge; Jiang, Zhi-Xin; Li, Jian-Hua

Macrophage autophagy plays an important role in the development of atherosclerosis, but the precise mechanism mediating this process is unclear. The potential role of the X-box binding protein 1 (XBP1), a crucial transduction factor that is involved in endoplasmic reticulum stress and the unfolded protein response, in bone marrow-derived macrophage autophagy is unknown. This study mainly explores the roles of XBP1 mRNA splicing in bone marrow-derived macrophage autophagy. The present study shows that the transient overexpression of spliced XBP1 via adenovirus-mediated gene transfer induces autophagy and promotes proliferation in bone marrow-derived macrophages via the down-regulation of Beclin-1, but that themore » sustained overexpression of spliced XBP1 leads to apoptosis. When XBP1 is down-regulated in bone marrow-derived macrophages using siRNA, rapamycin-induced autophagosome formation is ablated. Furthermore, we have detected the overexpression of XBP1 in areas of atherosclerotic plaques in the arteries of ApoE−/− mice. These results demonstrate that XBP1 mRNA splicing plays an important role in maintaining the function of bone marrow-derived macrophages and provide new insight into the study and treatment of atherosclerosis. - Highlights: • XBP1 was up-regulated in atherosclerotic plaques of ApoE−/− mice. • Transient spliced XBP1 overexpression induced macrophages autophagy via Beclin-1. • Sustained spliced XBP1 overexpression triggered macrophages apoptosis. • Spliced XBP1 plays a key role in maintaining the macrophages survival.« less

The value of eutherian-marsupial comparisons for understanding the function of glucocorticoids in female mammal reproduction.

PubMed

Fanson, Kerry V; Parrott, Marissa L

2015-11-01

This article is part of a Special Issue "SBN 2014". Chronic stress is known to inhibit female reproductive function. Consequently, it is often assumed that glucocorticoid (GC) concentrations should be negatively correlated with reproductive success because of the role they play in stress physiology. In contrast, a growing body of evidence indicates that GCs play an active role in promoting reproductive function. It is precisely because GCs are so integral to the entire process that disruptions to adrenal activity have negative consequences for reproduction. The goal of this paper is to draw attention to the increasing evidence showing that increases in adrenal activity are important for healthy female reproduction. Furthermore, we outline several hypotheses about the functional role(s) that GCs may play in mediating reproduction and argue that comparative studies between eutherian and marsupial mammals, which exhibit some pronounced differences in reproductive physiology, may be particularly useful for testing different hypotheses about the functional role of GCs in reproduction. Much of our current thinking about GCs and reproduction comes from research involving stress-induced levels of GCs and has led to broad assumptions about the effects of GCs on reproduction. Unfortunately, this has left a gaping hole in our knowledge about basal GC levels and how they may influence reproductive function, thereby preventing a broader understanding of adrenal physiology and obscuring potential solutions for reproductive dysfunction. Copyright © 2015 Elsevier Inc. All rights reserved.

The Hippocampus Supports High-Resolution Binding in the Service of Perception, Working Memory and Long-Term Memory

PubMed Central

Yonelinas, Andrew P.

2013-01-01

It is well established that the hippocampus plays a critical role in our ability to recollect past events. A number of recent studies have indicated that the hippocampus may also play a critical role in working memory and perception, but these results have been highly controversial because other similar studies have failed to find evidence for hippocampal involvement. Thus, the precise role that the hippocampus plays in cognition is still debated. In the current paper, I propose that the hippocampus supports the generation and utilization of complex high-resolution bindings that link together the qualitative aspects that make up an event; these bindings are essential for recollection, and they can also contribute to performance across a variety of tasks including perception and working memory. An examination of the existing patient literature provides support for this proposal by showing that hippocampal damage leads to impairments on perception and working memory tasks that require complex high-resolution bindings. Conversely, hippocampal damage is much less likely to lead to impairments on tasks that require only low-resolution or simple associations/relations. The current proposal can be distinguished from earlier accounts of hippocampal function, and it generates a number of novel predictions that can be tested in future studies. PMID:23721964

Application of CCD drift-scan photoelectric technique on monitoring GEO satellites

NASA Astrophysics Data System (ADS)

Yu, Yong; Zhao, Xiao-Fen; Luo, Hao; Mao, Yin-Dun; Tang, Zheng-Hong

2018-05-01

Geosynchronous Earth Orbit (GEO) satellites are widely used because of their unique characteristics of high-orbit and remaining permanently in the same area of the sky. Precise monitoring of GEO satellites can provide a key reference for the judgment of satellite operation status, the capture and identification of targets, and the analysis of collision warning. The observation using ground-based optical telescopes plays an important role in the field of monitoring GEO targets. Different from distant celestial bodies, there is a relative movement between the GEO target and the background reference stars, which makes the conventional observation method limited for long focal length telescopes. CCD drift-scan photoelectric technique is applied on monitoring GEO targets. In the case of parking the telescope, the good round images of the background reference stars and the GEO target at the same sky region can be obtained through the alternating observation of CCD drift-scan mode and CCD stare mode, so as to improve the precision of celestial positioning for the GEO target. Observation experiments of GEO targets were carried out with 1.56-meter telescope of Shanghai Astronomical Observatory. The results show that the application of CCD drift-scan photoelectric technique makes the precision of observing the GEO target reach the level of 0.2″, which gives full play to the advantage of the long focal length of the telescope. The effect of orbit improvement based on multi-pass of observations is obvious and the prediction precision of extrapolating to 72-h is in the order of several arc seconds in azimuth and elevation.

CCAAT/enhancer-binding protein α is required for hepatic outgrowth via the p53 pathway in zebrafish

PubMed Central

Yuan, Hao; Wen, Bin; Liu, Xiaohui; Gao, Ce; Yang, Ruimeng; Wang, Luxiang; Chen, Saijuan; Chen, Zhu; de The, Hugues; Zhou, Jun; Zhu, Jun

2015-01-01

CCAAT/enhancer-binding protein α (C/ebpα) is a transcription factor that plays important roles in the regulation of hepatogenesis, adipogenesis and hematopoiesis. Disruption of the C/EBPα gene in mice leads to disturbed liver architecture and neonatal death due to hypoglycemia. However, the precise stages of liver development affected by C/ebpα loss are poorly studied. Using the zebrafish embryo as a model organism, we show that inactivation of the cebpa gene by TALENs results in a small liver phenotype. Further studies reveal that C/ebpα is distinctively required for hepatic outgrowth but not for hepatoblast specification. Lack of C/ebpα leads to enhanced hepatic cell proliferation and subsequent increased cell apoptosis. Additional loss of p53 can largely rescue the hepatic defect in cebpa mutants, suggesting that C/ebpα plays a role in liver growth regulation via the p53 pathway. Thus, our findings for the first time demonstrate a stage-specific role for C/ebpα during liver organogenesis. PMID:26511037

NK cell subsets in autoimmune diseases.

PubMed

Zhang, Cai; Tian, Zhigang

2017-09-01

Natural killer (NK) cells are lymphocytes of the innate immune system. They not only exert cell-mediated cytotoxicity against tumor cells or infected cells, but also play regulatory role through promoting or suppressing functions of other immune cells by secretion of cytokines and chemokines. However, overactivation or dysfunction of NK cells may be associated with pathogenesis of some diseases. NK cells are found to act as a two edged weapon and play opposite roles with both regulatory and inducer activity in autoimmune diseases. Though the precise mechanisms for the opposite effects of NK cells has not been fully elucidated, the importance of NK cells in autoimmune diseases might be associated with different NK cell subsets, different tissue microenvironment and different stages of corresponding diseases. The local tissue microenvironment, unique cellular interactions and different stages of corresponding diseases shape the properties and function of NK cells. In this review, we focus on recent research on the features and function of different NK cell subsets, particularly tissue-resident NK cells in different tissues, and their potential role in autoimmune diseases. Copyright © 2017. Published by Elsevier Ltd.

CCAAT/enhancer-binding protein α is required for hepatic outgrowth via the p53 pathway in zebrafish.

PubMed

Yuan, Hao; Wen, Bin; Liu, Xiaohui; Gao, Ce; Yang, Ruimeng; Wang, Luxiang; Chen, Saijuan; Chen, Zhu; de The, Hugues; Zhou, Jun; Zhu, Jun

2015-10-29

CCAAT/enhancer-binding protein α (C/ebpα) is a transcription factor that plays important roles in the regulation of hepatogenesis, adipogenesis and hematopoiesis. Disruption of the C/EBPα gene in mice leads to disturbed liver architecture and neonatal death due to hypoglycemia. However, the precise stages of liver development affected by C/ebpα loss are poorly studied. Using the zebrafish embryo as a model organism, we show that inactivation of the cebpa gene by TALENs results in a small liver phenotype. Further studies reveal that C/ebpα is distinctively required for hepatic outgrowth but not for hepatoblast specification. Lack of C/ebpα leads to enhanced hepatic cell proliferation and subsequent increased cell apoptosis. Additional loss of p53 can largely rescue the hepatic defect in cebpa mutants, suggesting that C/ebpα plays a role in liver growth regulation via the p53 pathway. Thus, our findings for the first time demonstrate a stage-specific role for C/ebpα during liver organogenesis.

Inside story of Group I Metabotropic Glutamate Receptors (mGluRs).

PubMed

Bhattacharyya, Samarjit

2016-08-01

Metabotropic glutamate receptors (mGluRs) are G-protein coupled receptors (GPCRs) that are activated by the neurotransmitter glutamate in the central nervous system. Among the eight subtypes, mGluR1 and mGluR5 belong to the group I family. These receptors play important roles in the brain and are believed to be involved in multiple forms of experience dependent synaptic plasticity including learning and memory. In addition, group I mGluRs also have been implicated in various neuropsychiatric disorders like Fragile X syndrome, autism etc. The normal signaling depends on the precise location of these receptors in specific region of the neuron and the process of receptor trafficking plays a crucial role in controlling this localization. Intracellular trafficking could also regulate the desensitization, resensitization, down-regulation and intracellular signaling of these receptors. In this review I focus on the current understanding of group I mGluR regulation in the central nervous system and also their role in neuropsychiatric disorders. Copyright © 2016 Elsevier Ltd. All rights reserved.

The role played by serine proteases in the development and worsening of vascular complications in type 1 diabetes mellitus.

PubMed

Finotti, Paola

2006-08-01

Much attention has been given to the role played by serine proteases in the development and worsening of vascular complications in Type 1 diabetes mellitus. A generalized increase in proteolytic activity, either due to a true increase in concentration of specific proteases or defects of their protease inhibitors, represents an early marker of diabetes. However, the precise molecular mechanism whereby an unopposed proteolytic activity leads to overt vascular alterations has not fully been elucidated as yet. The picture is further complicated by the fact that, although sharing the same function, serine proteases constitute a structurally heterogeneous class of molecules. Besides classical proteases, for most part belonging to coagulative and fibrinolytic systems, other unrelated molecules exhibit serine-like protease activity and are capable of triggering both inflammatory and immune reactions. The specific role of these non classical serine proteases in the complex pathogenesis of diabetes and its vascular complications is attracting a new investigative interest, as these molecules may represent additional therapeutic targets. This review will focus on most recent acquisitions on this issue relevant to Type 1 diabetes.

Omics for Understanding the Gut-Liver-Microbiome Axis and Precision Medicine.

PubMed

Khalsa, Jag; Duffy, Linda C; Riscuta, Gabriela; Starke-Reed, Pamela; Hubbard, Van S

2017-03-01

Human metabolic disease opens a new view to understanding the contribution of the intestinal microbiome to drug metabolism and drug-induced toxicity in gut-liver function. The gut microbiome, a key determinant of intestinal inflammation, also plays a direct role in chronic inflammation and liver disease. Gut bacterial communities directly metabolize certain drugs, reducing their bioavailability and influencing individual variation in drug response. In addition, some microbiome-produced compounds may affect drug pharmacokinetics and pharmacodynamics via altered expression of metabolizing enzymes and drug transporters or genes coding for drug target proteins, drug response phenotypes, and disease states. Molecular-based high-throughput technologies are providing novel insight about host-gut microbiome interactions, homeostasis, and xenobiotic effects associated with wide variation in efficacy or toxicity in humans. It is envisioned that future approaches to treating and preventing liver disease will benefit from in-depth studies of the liver-microbiome axis. Thus, the microbiome shares a fundamental role in human physiology with various organ systems, and its importance must be considered in the rapid evolution of precision medicine. A new emerging perspective of understanding the effect of the gut microbiome on human response to drugs would be indispensable for developing efficacious, safe, and cost-effective precision therapies. © 2017, The American College of Clinical Pharmacology.

Driving reproduction: RFamide peptides behind the wheel.

PubMed

Kriegsfeld, Lance J

2006-12-01

The availability of tools for probing the genome and proteome more efficiently has allowed for the rapid discovery of novel genes and peptides that play important, previously uncharacterized roles in neuroendocrine regulation. In this review, the role of a class of neuropeptides containing the C-terminal Arg-Phe-NH(2) (RFamide) in regulating the reproductive axis will be highlighted. Neuropeptides containing the C-terminal Phe-Met-Arg-Phe-NH(2) (FMRFamide) were first identified as cardioregulatory elements in the bi-valve mollusk Macrocallista nimbosa. During the past two decades, numerous studies have shown the presence of structurally similar peptides sharing the RFamide motif across taxa. In vertebrates, RFamide peptides have pronounced influences on opiatergic regulation and neuroendocrine function. Two key peptides in this family are emerging as important regulators of the reproductive axis, kisspeptin and gonadotropin-inhibitory hormone (GnIH). Kisspeptin acts as the accelerator, directly driving gonadotropin-releasing hormone (GnRH) neurons, whereas GnIH acts as the restraint. Recent evidence suggests that both peptides play a role in mediating the negative feedback effects of sex steroids. This review presents the hypothesis that these peptides share complementary roles by responding to internal and external stimuli with opposing actions to precisely regulate the reproductive axis.

Driving Reproduction: RFamide Peptides Behind the Wheel

PubMed Central

Kriegsfeld, Lance J.

2012-01-01

The availability of tools for probing the genome and proteome more efficiently has allowed for the rapid discovery of novel genes and peptides that play important, previously-uncharacterized roles in neuroendocrine regulation. In this review, the role of a class of neuropeptides containing the C-terminal Arg-Phe-NH2 (RFamide) in regulating the reproductive axis will be highlighted. Neuropeptides containing the C-terminal Phe- Met-Arg-Phe-NH2 (FMRFamide) were first identified as cardioregulatory elements in the bi-valve mollusk, Macrocallista nimbosa. During the past two decades, numerous studies have shown the presence of structurally-similar peptides sharing the RFamide motif across taxa. In vertebrates, RFamide peptides have pronounced influences on opiatergic regulation and neuroendocrine function. Two key peptides in this family are emerging as important regulators of the reproductive axis, kisspeptin and gonadotropin-inhibitory hormone (GnIH). Kisspeptin acts as the accelerator, directly driving gonadotropin-releasing hormone (GnRH) neurons, whereas GnIH acts as the restraint. Recent evidence suggests that both peptides play a role in mediating the negative feedback effects of sex steroids. This review presents the hypothesis that these peptides share complementary roles by responding to internal and external stimuli with opposing actions to precisely regulate the reproductive axis. PMID:16876801

Pharmacological evidence is consistent with a prominent role of spatial memory in complex navigation

PubMed Central

2016-01-01

The ability to learn about the spatial environment plays an important role in navigation, migration, dispersal, and foraging. However, our understanding of both the role of cognition in the development of navigation strategies and the mechanisms underlying these strategies is limited. We tested the hypothesis that complex navigation is facilitated by spatial memory in a population of Chrysemys picta that navigate with extreme precision (±3.5 m) using specific routes that must be learned prior to age three. We used scopolamine, a muscarinic acetylcholine receptor antagonist, to manipulate the cognitive spatial abilities of free-living turtles during naturally occurring overland movements. Experienced adults treated with scopolamine diverted markedly from their precise navigation routes. Naive juveniles lacking experience (and memory) were not affected by scopolamine, and thereby served as controls for perceptual or non-spatial cognitive processes associated with navigation. Further, neither adult nor juvenile movement was affected by methylscopolamine, a form of scopolamine that does not cross the blood–brain barrier, a control for the peripheral effects of scopolamine. Together, these results are consistent with a role of spatial cognition in complex navigation and highlight a cellular mechanism that might underlie spatial cognition. Overall, our findings expand our understanding of the development of complex cognitive abilities of vertebrates and the neurological mechanisms of navigation. PMID:26865305

A Study of Particle Beam Spin Dynamics for High Precision Experiments

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

Fiedler, Andrew J.

In the search for physics beyond the Standard Model, high precision experiments to measure fundamental properties of particles are an important frontier. One group of such measurements involves magnetic dipole moment (MDM) values as well as searching for an electric dipole moment (EDM), both of which could provide insights about how particles interact with their environment at the quantum level and if there are undiscovered new particles. For these types of high precision experiments, minimizing statistical uncertainties in the measurements plays a critical role. \\\\ \\indent This work leverages computer simulations to quantify the effects of statistical uncertainty for experimentsmore » investigating spin dynamics. In it, analysis of beam properties and lattice design effects on the polarization of the beam is performed. As a case study, the beam lines that will provide polarized muon beams to the Fermilab Muon \\emph{g}-2 experiment are analyzed to determine the effects of correlations between the phase space variables and the overall polarization of the muon beam.« less

Precision muon physics

NASA Astrophysics Data System (ADS)

Gorringe, T. P.; Hertzog, D. W.

2015-09-01

The muon is playing a unique role in sub-atomic physics. Studies of muon decay both determine the overall strength and establish the chiral structure of weak interactions, as well as setting extraordinary limits on charged-lepton-flavor-violating processes. Measurements of the muon's anomalous magnetic moment offer singular sensitivity to the completeness of the standard model and the predictions of many speculative theories. Spectroscopy of muonium and muonic atoms gives unmatched determinations of fundamental quantities including the magnetic moment ratio μμ /μp, lepton mass ratio mμ /me, and proton charge radius rp. Also, muon capture experiments are exploring elusive features of weak interactions involving nucleons and nuclei. We will review the experimental landscape of contemporary high-precision and high-sensitivity experiments with muons. One focus is the novel methods and ingenious techniques that achieve such precision and sensitivity in recent, present, and planned experiments. Another focus is the uncommonly broad and topical range of questions in atomic, nuclear and particle physics that such experiments explore.

Access Control in Location-Based Services

NASA Astrophysics Data System (ADS)

Ardagna, Claudio A.; Cremonini, Marco; de Capitani di Vimercati, Sabrina; Samarati, Pierangela

Recent enhancements in location technologies reliability and precision are fostering the development of a new wave of applications that make use of the location information of users. Such applications introduces new aspects of access control which should be addressed. On the one side, precise location information may play an important role and can be used to develop Location-based Access Control (LBAC) systems that integrate traditional access control mechanisms with conditions based on the physical position of users. On the other side, location information of users can be considered sensitive and access control solutions should be developed to protect it against unauthorized accesses and disclosures. In this chapter, we address these two aspects related to the use and protection of location information, discussing existing solutions, open issues, and some research directions.

VEGF ameliorates the ataxic phenotype in spinocerebellar ataxia type 1 (SCA1) mice

PubMed Central

Cvetanovic, Marija; Patel, Jay; Marti, Hugo H; Kini, Ameet R; Opal, Puneet

2012-01-01

SCA1 is an adult-onset, dominantly inherited neurodegenerative disease caused by expansion of a glutamine repeat tract in ATXN1. Although the precise function of ATXN1 remains elusive, it appears to play a role in transcriptional repression. We find that mutant ATXN1 suppresses transcription of the neurotrophic and angiogenic factor VEGF. We also show that genetic or pharmacologic replenishment of VEGF mitigates SCA1 pathogenesis, suggesting a novel therapeutic strategy for this incurable disease. PMID:22001907

Sensitivity, Specificity, PPV, and NPV for Predictive Biomarkers

PubMed Central

2015-01-01

Molecularly targeted cancer drugs are often developed with companion diagnostics that attempt to identify which patients will have better outcome on the new drug than the control regimen. Such predictive biomarkers are playing an increasingly important role in precision oncology. For diagnostic tests, sensitivity, specificity, positive predictive value, and negative predictive are usually used as performance measures. This paper discusses these indices for predictive biomarkers, provides methods for their calculation with survival or response endpoints, and describes assumptions involved in their use. PMID:26109105

Controlling magnetism of a complex metallic system using atomic individualism.

PubMed

Mudryk, Y; Paudyal, D; Pecharsky, V K; Gschneidner, K A; Misra, S; Miller, G J

2010-08-06

When the complexity of a metallic compound reaches a certain level, a specific location in the structure may be critically responsible for a given fundamental property of a material while other locations may not play as much of a role in determining such a property. The first-principles theory has pinpointed a critical location in the framework of a complex intermetallic compound--Gd(5)Ge(4)--that resulted in a controlled alteration of the magnetism of this compound using precise chemical tools.

Controlling Magnetism of a Complex Metallic System Using Atomic Individualism

NASA Astrophysics Data System (ADS)

Mudryk, Y.; Paudyal, D.; Pecharsky, V. K.; Gschneidner, K. A., Jr.; Misra, S.; Miller, G. J.

2010-08-01

When the complexity of a metallic compound reaches a certain level, a specific location in the structure may be critically responsible for a given fundamental property of a material while other locations may not play as much of a role in determining such a property. The first-principles theory has pinpointed a critical location in the framework of a complex intermetallic compound—Gd5Ge4—that resulted in a controlled alteration of the magnetism of this compound using precise chemical tools.

Precise GPS orbits for geodesy

NASA Technical Reports Server (NTRS)

Colombo, Oscar L.

1994-01-01

The Global Positioning System (GPS) has become, in recent years, the main space-based system for surveying and navigation in many military, commercial, cadastral, mapping, and scientific applications. Better receivers, interferometric techniques (DGPS), and advances in post-processing methods have made possible to position fixed or moving receivers with sub-decimeter accuracies in a global reference frame. Improved methods for obtaining the orbits of the GPS satellites have played a major role in these achievements; this paper gives a personal view of the main developments in GPS orbit determination.

Flash melting of tantalum in a diamond cell to 85 GPa

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

Karandikar, Amol; Boehler, Reinhard

2016-02-09

Here, we demonstrate a new level of precision in measuring melting temperatures at high pressure using laser flash-heating followed by Scanning Electron Microscopy and Focused Ion Beam Milling. Furthermore, the new measurements on tantalum put unprecedented constraints on its highly debated melting slope, calling for a reevaluation of theoretical, shock compression and diamond cell approaches to determine melting at high pressure. X-ray analysis of the recovered samples confirmed the absence of chemical reactions, which likely played a significant role in previous experiments.

Architectural design proposal for real time clock for wireless microcontroller unit

NASA Astrophysics Data System (ADS)

Alias, Muhammad Nor Azwan Mohd; Nizam Mohyar, Shaiful

2017-11-01

In this project, we are developing an Intellectual properties (IP) which is a dedicated real-time clock (RTC) system for a wireless microcontroller. This IP is developed using Verilog Hardware Description Language (Verilog HDL) and being simulated using Quartus II and Synopsys software. This RTC will be used in microcontroller system to provide precise time and date which can be used for various applications. It plays a very important role in the real-time systems like digital clock, attendance system, digital camera and more.

On unified modeling, theory, and method for solving multi-scale global optimization problems

NASA Astrophysics Data System (ADS)

Gao, David Yang

2016-10-01

A unified model is proposed for general optimization problems in multi-scale complex systems. Based on this model and necessary assumptions in physics, the canonical duality theory is presented in a precise way to include traditional duality theories and popular methods as special applications. Two conjectures on NP-hardness are proposed, which should play important roles for correctly understanding and efficiently solving challenging real-world problems. Applications are illustrated for both nonconvex continuous optimization and mixed integer nonlinear programming.

Text Mining for Precision Medicine: Bringing structure to EHRs and biomedical literature to understand genes and health

PubMed Central

Simmons, Michael; Singhal, Ayush; Lu, Zhiyong

2018-01-01

The key question of precision medicine is whether it is possible to find clinically actionable granularity in diagnosing disease and classifying patient risk. The advent of next generation sequencing and the widespread adoption of electronic health records (EHRs) have provided clinicians and researchers a wealth of data and made possible the precise characterization of individual patient genotypes and phenotypes. Unstructured text — found in biomedical publications and clinical notes — is an important component of genotype and phenotype knowledge. Publications in the biomedical literature provide essential information for interpreting genetic data. Likewise, clinical notes contain the richest source of phenotype information in EHRs. Text mining can render these texts computationally accessible and support information extraction and hypothesis generation. This chapter reviews the mechanics of text mining in precision medicine and discusses several specific use cases, including database curation for personalized cancer medicine, patient outcome prediction from EHR-derived cohorts, and pharmacogenomic research. Taken as a whole, these use cases demonstrate how text mining enables effective utilization of existing knowledge sources and thus promotes increased value for patients and healthcare systems. Text mining is an indispensable tool for translating genotype-phenotype data into effective clinical care that will undoubtedly play an important role in the eventual realization of precision medicine. PMID:27807747

Text Mining for Precision Medicine: Bringing Structure to EHRs and Biomedical Literature to Understand Genes and Health.

PubMed

Simmons, Michael; Singhal, Ayush; Lu, Zhiyong

2016-01-01

The key question of precision medicine is whether it is possible to find clinically actionable granularity in diagnosing disease and classifying patient risk. The advent of next-generation sequencing and the widespread adoption of electronic health records (EHRs) have provided clinicians and researchers a wealth of data and made possible the precise characterization of individual patient genotypes and phenotypes. Unstructured text-found in biomedical publications and clinical notes-is an important component of genotype and phenotype knowledge. Publications in the biomedical literature provide essential information for interpreting genetic data. Likewise, clinical notes contain the richest source of phenotype information in EHRs. Text mining can render these texts computationally accessible and support information extraction and hypothesis generation. This chapter reviews the mechanics of text mining in precision medicine and discusses several specific use cases, including database curation for personalized cancer medicine, patient outcome prediction from EHR-derived cohorts, and pharmacogenomic research. Taken as a whole, these use cases demonstrate how text mining enables effective utilization of existing knowledge sources and thus promotes increased value for patients and healthcare systems. Text mining is an indispensable tool for translating genotype-phenotype data into effective clinical care that will undoubtedly play an important role in the eventual realization of precision medicine.

High precision during food recruitment of experienced (reactivated) foragers in the stingless bee Scaptotrigona mexicana (Apidae, Meliponini)

NASA Astrophysics Data System (ADS)

Sánchez, Daniel; Nieh, James C.; Hénaut, Yann; Cruz, Leopoldo; Vandame, Rémy

Several studies have examined the existence of recruitment communication mechanisms in stingless bees. However, the spatial accuracy of location-specific recruitment has not been examined. Moreover, the location-specific recruitment of reactivated foragers, i.e., foragers that have previously experienced the same food source at a different location and time, has not been explicitly examined. However, such foragers may also play a significant role in colony foraging, particularly in small colonies. Here we report that reactivated Scaptotrigona mexicana foragers can recruit with high precision to a specific food location. The recruitment precision of reactivated foragers was evaluated by placing control feeders to the left and the right of the training feeder (direction-precision tests) and between the nest and the training feeder and beyond it (distance-precision tests). Reactivated foragers arrived at the correct location with high precision: 98.44% arrived at the training feeder in the direction trials (five-feeder fan-shaped array, accuracy of at least +/-6° of azimuth at 50 m from the nest), and 88.62% arrived at the training feeder in the distance trials (five-feeder linear array, accuracy of at least +/-5 m or +/-10% at 50 m from the nest). Thus, S. mexicana reactivated foragers can find the indicated food source at a specific distance and direction with high precision, higher than that shown by honeybees, Apis mellifera, which do not communicate food location at such close distances to the nest.

Radiosurgery and radiotherapy for sacral tumors.

PubMed

Gibbs, Iris C; Chang, Steven D

2003-08-15

Sacral tumors represent a small subset of spinal lesions and typically include chordomas, metastases, other primary bone tumors, and benign schwannomas. Resection is the standard treatment for many sacral tumors, but many types of sacral lesions have the potential for recurrence after excision. In these cases, adjuvant radiotherapy is often beneficial. Although conventional radiotherapy plays an important role in the management of spinal lesions, the radiation doses required for adequate local control of many sacral lesions generally exceed the tolerance doses of normal tissues, thus limiting its definitive role in the management of sacral tumors. Recent advances in the field of stereotactic radiosurgery have allowed precise targeting of the sacrum. In this report the authors review the use of these two forms of radiation treatment and their role in managing sacral tumors.

Provenance Usage in the OceanLink Project

NASA Astrophysics Data System (ADS)

Narock, T.; Arko, R. A.; Carbotte, S. M.; Chandler, C. L.; Cheatham, M.; Fils, D.; Finin, T.; Hitzler, P.; Janowicz, K.; Jones, M.; Krisnadhi, A.; Lehnert, K. A.; Mickle, A.; Raymond, L. M.; Schildhauer, M.; Shepherd, A.; Wiebe, P. H.

2014-12-01

A wide spectrum of maturing methods and tools, collectively characterized as the Semantic Web, is helping to vastly improve thedissemination of scientific research. The OceanLink project, an NSF EarthCube Building Block, is utilizing semantic technologies tointegrate geoscience data repositories, library holdings, conference abstracts, and funded research awards. Provenance is a vital componentin meeting both the scientific and engineering requirements of OceanLink. Provenance plays a key role in justification and understanding when presenting users with results aggregated from multiple sources. In the engineering sense, provenance enables the identification of new data and the ability to determine which data sources to query. Additionally, OceanLink will leverage human and machine computation for crowdsourcing, text mining, and co-reference resolution. The results of these computations, and their associated provenance, will be folded back into the constituent systems to continually enhance precision and utility. We will touch on the various roles provenance is playing in OceanLink as well as present our use of the PROV Ontology and associated Ontology Design Patterns.

Dendritic small conductance calcium-activated potassium channels activated by action potentials suppress EPSPs and gate spike-timing dependent synaptic plasticity.

PubMed

Jones, Scott L; To, Minh-Son; Stuart, Greg J

2017-10-23

Small conductance calcium-activated potassium channels (SK channels) are present in spines and can be activated by backpropagating action potentials (APs). This suggests they may play a critical role in spike-timing dependent synaptic plasticity (STDP). Consistent with this idea, EPSPs in both cortical and hippocampal pyramidal neurons were suppressed by preceding APs in an SK-dependent manner. In cortical pyramidal neurons EPSP suppression by preceding APs depended on their precise timing as well as the distance of activated synapses from the soma, was dendritic in origin, and involved SK-dependent suppression of NMDA receptor activation. As a result SK channel activation by backpropagating APs gated STDP induction during low-frequency AP-EPSP pairing, with both LTP and LTD absent under control conditions but present after SK channel block. These findings indicate that activation of SK channels in spines by backpropagating APs plays a key role in regulating both EPSP amplitude and STDP induction.

First Direct Measurement of C 12 ( C 12 , n ) Mg 23 at Stellar Energies

DOE PAGES

Bucher, B.; Tang, X. D.; Fang, X.; ...

2015-06-25

Neutrons produced by the carbon fusion reaction 12C( 12C,n) 23Mg play an important role in stellar nucleosynthesis. However, past studies have shown large discrepancies between experimental data and theory, leading to an uncertain cross section extrapolation at astrophysical energies. Here in this paper, we present the first direct measurement that extends deep into the astrophysical energy range along with a new and improved extrapolation technique based on experimental data from the mirror reaction 12C( 12C,p) 23Na . The new reaction rate has been determined with a well-defined uncertainty that exceeds the precision required by astrophysics models. Using our constrained rate,more » we find that 12C ( 12C,n) 23Mg is crucial to the production of Na and Al in pop-III pair instability supernovae. It also plays a nonnegligible role in the production of weak s -process elements, as well as in the production of the important galactic γ-ray emitter 60Fe.« less

Visual tracking strategies for intelligent vehicle highway systems

NASA Astrophysics Data System (ADS)

Smith, Christopher E.; Papanikolopoulos, Nikolaos P.; Brandt, Scott A.; Richards, Charles

1995-01-01

The complexity and congestion of current transportation systems often produce traffic situations that jeopardize the safety of the people involved. These situations vary from maintaining a safe distance behind a leading vehicle to safely allowing a pedestrian to cross a busy street. Environmental sensing plays a critical role in virtually all of these situations. Of the sensors available, vision sensors provide information that is richer and more complete than other sensors, making them a logical choice for a multisensor transportation system. In this paper we present robust techniques for intelligent vehicle-highway applications where computer vision plays a crucial role. In particular, we demonstrate that the controlled active vision framework can be utilized to provide a visual sensing modality to a traffic advisory system in order to increase the overall safety margin in a variety of common traffic situations. We have selected two application examples, vehicle tracking and pedestrian tracking, to demonstrate that the framework can provide precisely the type of information required to effectively manage the given situation.

Hospital nursing leadership-led interventions increased genomic awareness and educational intent in Magnet settings.

PubMed

Calzone, Kathleen A; Jenkins, Jean; Culp, Stacey; Badzek, Laurie

2017-11-13

The Precision Medicine Initiative will accelerate genomic discoveries that improve health care, necessitating a genomic competent workforce. This study assessed leadership team (administrator/educator) year-long interventions to improve registered nurses' (RNs) capacity to integrate genomics into practice. We examined genomic competency outcomes in 8,150 RNs. Awareness and intention to learn more increased compared with controls. Findings suggest achieving genomic competency requires a longer intervention and support strategies such as infrastructure and policies. Leadership played a role in mobilizing staff, resources, and supporting infrastructure to sustain a large-scale competency effort on an institutional basis. Results demonstrate genomic workforce competency can be attained with leadership support and sufficient time. Our study provides evidence of the critical role health-care leaders play in facilitating genomic integration into health care to improve patient outcomes. Genomics' impact on quality, safety, and cost indicate a leader-initiated national competency effort is achievable and warranted. Published by Elsevier Inc.

The Principle-Based Method of Practical Ethics.

PubMed

Spielthenner, Georg

2017-09-01

This paper is about the methodology of doing practical ethics. There is a variety of methods employed in ethics. One of them is the principle-based approach, which has an established place in ethical reasoning. In everyday life, we often judge the rightness and wrongness of actions by their conformity to principles, and the appeal to principles plays a significant role in practical ethics, too. In this paper, I try to provide a better understanding of the nature of principle-based reasoning. To accomplish this, I show in the first section that these principles can be applied to cases in a meaningful and sufficiently precise way. The second section discusses the question how relevant applying principles is to the resolution of ethical issues. This depends on their nature. I argue that the principles under consideration in this paper should be interpreted as presumptive principles and I conclude that although they cannot be expected to bear the weight of definitely resolving ethical problems, these principles can nevertheless play a considerable role in ethical research.

The logic of communication: roles for mobile transcription factors in plants.

PubMed

Long, Yuchen; Scheres, Ben; Blilou, Ikram

2015-02-01

Mobile transcription factors play many roles in plant development. Here, we compare the use of mobile transcription factors as signals with some canonical signal transduction processes in prokaryotes and eukaryotes. After an initial survey, we focus on the SHORT-ROOT pathway in Arabidopsis roots to show that, despite the simplicity of the concept of mobile transcription factor signalling, many lines of evidence reveal a surprising complexity in control mechanisms linked to this process. We argue that these controls bestow precision, robustness, and versatility on mobile transcription factor signalling. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Role of the MAGUK protein family in synapse formation and function.

PubMed

Oliva, Carlos; Escobedo, Pía; Astorga, César; Molina, Claudia; Sierralta, Jimena

2012-01-01

Synaptic function is crucially dependent on the spatial organization of the presynaptic and postsynaptic apparatuses and the juxtaposition of both membrane compartments. This precise arrangement is achieved by a protein network at the submembrane region of each cell that is built around scaffold proteins. The membrane-associated guanylate kinase (MAGUK) family of proteins is a widely expressed and well-conserved group of proteins that plays an essential role in the formation and regulation of this scaffolding. Here, we review general features of this protein family, focusing on the discs large and calcium/calmodulin-dependent serine protein kinase subfamilies of MAGUKs in the formation, function, and plasticity of synapses. Copyright © 2011 Wiley Periodicals, Inc.

Opioidergic mechanisms are not involved in the antihyperalgesic effects of carbamazepine and oxcarbazepine.

PubMed

Stepanovic-Petrovic, Radica M; Tomic, M A; Vuckovic, S M; Ugresic, N D; Prostran, M S; Boskovic, B

2007-04-01

The mechanisms of the analgesic action of carbamazepine and oxcarbazepine, in particular the role of opioid receptors, have not been established precisely. The systemic effects of naloxone, an opioid receptor antagonist, on the antihyperalgesic effects of carbamazepine and oxcarbazepine were examined in the model of inflammatory hyperalgesia induced by the intraplantar (i.pl.) administration of concanavaline A (Con A, 0.8 mg/paw) into the rat hind paw. Naloxone (3 mg/kg; i.p.) did not alter the antihyperalgesic effects of either carbamazepine or oxcarbazepine. These results indicate that the opioid system of pain modulation does not play a significant role in the antihyperalgesic effects of carbamazepine and oxcarbazepine.

The Role of Reflectance Confocal Microscopy in Clinical Trials for Tumor Monitoring.

PubMed

Guilera, Josep Malvehy; Barreiro Capurro, Alicia; Carrera Alvárez, Cristina; Puig Sardá, Susana

2016-10-01

Reflectance confocal microscopy (RCM) allows the evaluation with superb accuracy of some skin tumors before, during, and after treatment. In clinical trials RCM has been shown to provide useful information for evaluation of efficacy of topical or systemic medication. With the recent introduction of handheld RCM a fast examination of the tumor can be done in minutes. In patients treated with surgery RCM plays a unique role to precisely map margins of the tumor in the skin surface and for the detection of subclinical recurrences. This article reviews the use of RCM in the research of different skin cancer tumor treatments. Copyright © 2016. Published by Elsevier Inc.

Network-based machine learning and graph theory algorithms for precision oncology.

PubMed

Zhang, Wei; Chien, Jeremy; Yong, Jeongsik; Kuang, Rui

2017-01-01

Network-based analytics plays an increasingly important role in precision oncology. Growing evidence in recent studies suggests that cancer can be better understood through mutated or dysregulated pathways or networks rather than individual mutations and that the efficacy of repositioned drugs can be inferred from disease modules in molecular networks. This article reviews network-based machine learning and graph theory algorithms for integrative analysis of personal genomic data and biomedical knowledge bases to identify tumor-specific molecular mechanisms, candidate targets and repositioned drugs for personalized treatment. The review focuses on the algorithmic design and mathematical formulation of these methods to facilitate applications and implementations of network-based analysis in the practice of precision oncology. We review the methods applied in three scenarios to integrate genomic data and network models in different analysis pipelines, and we examine three categories of network-based approaches for repositioning drugs in drug-disease-gene networks. In addition, we perform a comprehensive subnetwork/pathway analysis of mutations in 31 cancer genome projects in the Cancer Genome Atlas and present a detailed case study on ovarian cancer. Finally, we discuss interesting observations, potential pitfalls and future directions in network-based precision oncology.

Dotette: Programmable, high-precision, plug-and-play droplet pipetting.

PubMed

Fan, Jinzhen; Men, Yongfan; Hao Tseng, Kuo; Ding, Yi; Ding, Yunfeng; Villarreal, Fernando; Tan, Cheemeng; Li, Baoqing; Pan, Tingrui

2018-05-01

Manual micropipettes are the most heavily used liquid handling devices in biological and chemical laboratories; however, they suffer from low precision for volumes under 1  μ l and inevitable human errors. For a manual device, the human errors introduced pose potential risks of failed experiments, inaccurate results, and financial costs. Meanwhile, low precision under 1  μ l can cause severe quantification errors and high heterogeneity of outcomes, becoming a bottleneck of reaction miniaturization for quantitative research in biochemical labs. Here, we report Dotette, a programmable, plug-and-play microfluidic pipetting device based on nanoliter liquid printing. With automated control, protocols designed on computers can be directly downloaded into Dotette, enabling programmable operation processes. Utilizing continuous nanoliter droplet dispensing, the precision of the volume control has been successfully improved from traditional 20%-50% to less than 5% in the range of 100 nl to 1000 nl. Such a highly automated, plug-and-play add-on to existing pipetting devices not only improves precise quantification in low-volume liquid handling and reduces chemical consumptions but also facilitates and automates a variety of biochemical and biological operations.

Evolving issues in the management of reflux disease?

PubMed

Yuan, Yuhong; Hunt, Richard H

2009-07-01

Gastroesophageal reflux disease (GERD) is a common chronic disorder often successfully treated, although there are several evolving issues in management. We reviewed the issues related to unmet needs over the past 12 months. A substantial number of patients fail to respond adequately to once or even twice daily proton pump inhibitor (PPI). There is no standard definition of PPI failure in GERD; a universally accepted definition for treatment success is also not available. Differentiation between erosive esophagitis and nonerosive reflux disease can be made but requires endoscopy; but studies still confuse functional heartburn and nonerosive reflux disease, which impacts management. Acid reflux plays an important role in GERD pathogenesis and the precise role of acid requires more studies of differences between erosive esophagitis and nonerosive reflux disease symptom generation and the implication of nocturnal acidification. Several possible mechanisms may explain GERD refractory to PPIs. Management of PPI nonresponders remains a challenge. Objective and precise evaluation of symptoms and treatment response requires study in high-quality trials. New therapeutic approaches are under investigation to answer unmet needs and improve erosive esophagitis healing rates and symptom control.

Metabolic scaling and biodiversity of forests

NASA Astrophysics Data System (ADS)

Banavar, Jayanth

Forests are biologically diverse and play a critical role in the dynamics of earth-climate systems. A forest is a tremendously complex system comprising co-existing rooted trees of many species and many sizes and utilizing resources from the environment. The trees interact with each other and with their environment and the interactions are not precisely known. Using scaling ideas, we will present a theoretical framework for understanding the role of geometry in determining the metabolic rate of a tree and of a forest. The quantification of tropical tree biodiversity and their abundances is still an open and challenging problem. Using a global-scale compilation, we will present a method that allows one to predict, from local censuses, the biodiversity and patterns of species abundance at the whole forest scale. The method allows one to quantify the minimum percentage cover of the forest that should be sampled in order to have a precise prediction of the estimates of biodiversity and species abundances. Collaborators: Amos Maritan, Tommaso Anfodillo, Sandro Azaele, Marco Favretti, Marco Formentin, Jacopo Grilli, Samir Suweis, Anna Tovo, Igor Volkov.

Camera Calibration with Radial Variance Component Estimation

NASA Astrophysics Data System (ADS)

Mélykuti, B.; Kruck, E. J.

2014-11-01

Camera calibration plays a more and more important role in recent times. Beside real digital aerial survey cameras the photogrammetric market is dominated by a big number of non-metric digital cameras mounted on UAVs or other low-weight flying platforms. The in-flight calibration of those systems has a significant role to enhance the geometric accuracy of survey photos considerably. It is expected to have a better precision of photo measurements in the center of images then along the edges or in the corners. With statistical methods the accuracy of photo measurements in dependency of the distance of points from image center has been analyzed. This test provides a curve for the measurement precision as function of the photo radius. A high number of camera types have been tested with well penetrated point measurements in image space. The result of the tests led to a general consequence to show a functional connection between accuracy and radial distance and to give a method how to check and enhance the geometrical capability of the cameras in respect to these results.

In vivo short-term precision of hip structure analysis variables in comparison with bone mineral density using paired dual-energy X-ray absorptiometry scans from multi-center clinical trials.

PubMed

Khoo, Benjamin C C; Beck, Thomas J; Qiao, Qi-Hong; Parakh, Pallav; Semanick, Lisa; Prince, Richard L; Singer, Kevin P; Price, Roger I

2005-07-01

Hip structural analysis (HSA) is a technique for extracting strength-related structural dimensions of bone cross-sections from two-dimensional hip scan images acquired by dual energy X-ray absorptiometry (DXA) scanners. Heretofore the precision of the method has not been thoroughly tested in the clinical setting. Using paired scans from two large clinical trials involving a range of different DXA machines, this study reports the first precision analysis of HSA variables, in comparison with that of conventional bone mineral density (BMD) on the same scans. A key HSA variable, section modulus (Z), biomechanically indicative of bone strength during bending, had a short-term precision percentage coefficient of variation (CV%) in the femoral neck of 3.4-10.1%, depending on the manufacturer or model of the DXA equipment. Cross-sectional area (CSA), a determinant of bone strength during axial loading and closely aligned with conventional DXA bone mineral content, had a range of CV% from 2.8% to 7.9%. Poorer precision was associated with inadequate inclusion of the femoral shaft or femoral head in the DXA-scanned hip region. Precision of HSA-derived BMD varied between 2.4% and 6.4%. Precision of DXA manufacturer-derived BMD varied between 1.9% and 3.4%, arising from the larger analysis region of interest (ROI). The precision of HSA variables was not generally dependent on magnitude, subject height, weight, or conventional femoral neck densitometric variables. The generally poorer precision of key HSA variables in comparison with conventional DXA-derived BMD highlights the critical roles played by correct limb repositioning and choice of an adequate and appropriately positioned ROI.

Rac-WAVE-mediated actin reorganization is required for organization and maintenance of cell-cell adhesion.

PubMed

Yamazaki, Daisuke; Oikawa, Tsukasa; Takenawa, Tadaomi

2007-01-01

During cadherin-dependent cell-cell adhesion, the actin cytoskeleton undergoes dynamic reorganization in epithelial cells. Rho-family small GTPases, which regulate actin dynamics, play pivotal roles in cadherin-dependent cell-cell adhesion; however, the precise molecular mechanisms that underlie cell-cell adhesion formation remain unclear. Here we show that Wiskott-Aldrich syndrome protein family verprolin-homologous protein (WAVE)-mediated reorganization of actin, downstream of Rac plays an important role in normal development of cadherin-dependent cell-cell adhesions in MDCK cells. Rac-induced development of cadherin-dependent adhesions required WAVE2-dependent actin reorganization. The process of cell-cell adhesion is divided into three steps: formation of new cell-cell contacts, stabilization of these new contacts and junction maturation. WAVE1 and WAVE2 were expressed in MDCK cells. The functions of WAVE1 and WAVE2 were redundant in this system but WAVE2 appeared to play a more significant role. During the first step, WAVE2-dependent lamellipodial protrusions facilitated formation of cell-cell contacts. During the second step, WAVE2 recruited actin filaments to new cell-cell contacts and stabilized newly formed cadherin clusters. During the third step, WAVE2-dependent actin reorganization was required for organization and maintenance of mature cell-cell adhesions. Thus, Rac-WAVE-dependent actin reorganization is not only involved in formation of cell-cell adhesions but is also required for their maintenance.

Molecular imaging of the tumor microenvironment for precision medicine and theranostics.

PubMed

Penet, Marie-France; Krishnamachary, Balaji; Chen, Zhihang; Jin, Jiefu; Bhujwalla, Zaver M

2014-01-01

Morbidity and mortality from cancer and their associated conditions and treatments continue to extract a heavy social and economic global burden despite the transformative advances in science and technology in the twenty-first century. In fact, cancer incidence and mortality are expected to reach pandemic proportions by 2025, and costs of managing cancer will escalate to trillions of dollars. The inability to establish effective cancer treatments arises from the complexity of conditions that exist within tumors, the plasticity and adaptability of cancer cells coupled with their ability to escape immune surveillance, and the co-opted stromal cells and microenvironment that assist cancer cells in survival. Stromal cells, although destroyed together with cancer cells, have an ever-replenishing source that can assist in resurrecting tumors from any residual cancer cells that may survive treatment. The tumor microenvironment landscape is a continually changing landscape, with spatial and temporal heterogeneities that impact and influence cancer treatment outcome. Importantly, the changing landscape of the tumor microenvironment can be exploited for precision medicine and theranostics. Molecular and functional imaging can play important roles in shaping and selecting treatments to match this landscape. Our purpose in this review is to examine the roles of molecular and functional imaging, within the context of the tumor microenvironment, and the feasibility of their applications for precision medicine and theranostics in humans. © 2014 Elsevier Inc. All rights reserved.

Challenges to studying the health effects of early life environmental chemical exposures on children's health.

PubMed

Braun, Joseph M; Gray, Kimberly

2017-12-01

Epidemiological studies play an important role in quantifying how early life environmental chemical exposures influence the risk of childhood diseases. These studies face at least four major challenges that can produce noise when trying to identify signals of associations between chemical exposure and childhood health. Challenges include accurately estimating chemical exposure, confounding from causes of both exposure and disease, identifying periods of heightened vulnerability to chemical exposures, and determining the effects of chemical mixtures. We provide recommendations that will aid in identifying these signals with more precision.

Fetal MRI at 3T—ready for routine use?

PubMed Central

Weisstanner, Christian; Gruber, Gerlinde M; Brugger, Peter C; Mitter, Christan; Diogo, Mariana C; Kasprian, Gregor

2017-01-01

Fetal MR now plays an important role in the clinical work-up of pregnant females. It is performed mainly at 1.5 T. However, the desire to obtain a more precise fetal depiction or the fact that some institutions have access only to a 3.0 T scanner has resulted in a growing interest in performing fetal MR at 3.0 T. The aim of this article was to provide a reference for the use of 3.0 T MRI as a prenatal diagnostic method. PMID:27768394

Using Time Evolution of the Bunch Structure to Extract the Muon Momentum Distribution in the Fermilab Muon g-2 Experiment

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

Wu, W.; Quinn, B.; Crnkovic, J. D.

Beam dynamics plays an important role in achieving the unprecedented precision on measurement of the muon anomalous magnetic moment in the Fermilab Muon g-2 Experiment. It needs to find the muon momentum distribution in the storage ring in order to evaluate the electric field correction to muon anomalous precession frequency. We will show how to use time evolution of the beam bunch structure to extract the muon momentum distribution by applying a fast rotation analysis on the decay electron signals.

Performance of high power S-band klystrons focused with permanent magnet

NASA Astrophysics Data System (ADS)

Fukuda, S.; Shidara, T.; Saito, Y.; Hanaki, H.; Nakao, K.; Homma, H.; Anami, S.; Tanaka, J.

1987-02-01

Performance of high power S-band klystrons focused with permanent magnet is presented. The axial magnetic field distribution and the transverse magnetic field play an important role in the tube performance. Effects of the reversal field in the collector and the cathode-anode region are discussed precisely. It is also shown that the tube efficiency is strongly affected with the residual transverse magnetic field. The allowable transverse field is less than 0.3 percent of the longitudinal field in the entire RF interaction region of the klystron.

Primary Mural Endocarditis Without Valvular Involvement.

PubMed

Tahara, Mai; Nagai, Tomoo; Takase, Yoshiyuki; Takiguchi, Shunichi; Tanaka, Yoshiaki; Kunihara, Takashi; Arakawa, Junko; Nakaya, Kazuhiro; Hamabe, Akira; Gatate, Youdou; Kujiraoka, Takehiko; Tabata, Hirotsugu; Katsushika, Shuichi

2017-03-01

Primary mural endocarditis is an extremely rare infection in which nonvalvular endocardial involvement is seen without any cardiac structural abnormalities such as ventricular septal defects. The rapid and precise diagnosis of this disease remains challenging. We present 2 cases (67- and 47-year-old male patients) of pathologically confirmed primary mural endocarditis that could have been detected by initial transthoracic echocardiography in the emergency department. Transthoracic echocardiography and transesophageal echocardiography play critical roles in the early recognition and confirmation of primary mural endocarditis. © 2017 by the American Institute of Ultrasound in Medicine.

Molecular mechanisms of action of bacterial exotoxins.

PubMed

Balfanz, J; Rautenberg, P; Ullmann, U

1996-07-01

Toxins are one of the inventive strategies that bacteria have developed in order to survive. As virulence factors, they play a major role in the pathogenesis of infectious diseases. Recent discoveries have once more highlighted the effectiveness of these precisely adjusted bacterial weapons. Furthermore, toxins have become an invaluable tool in the investigation of fundamental cell processes, including regulation of cellular functions by various G proteins, cytoskeletal dynamics and neural transmission. In this review, the bacterial toxins are presented in a rational classification based on the molecular mechanisms of action.

Nonsurgical Rejuvenation of the Eyelids with Hyaluronic Acid Gel Injections

PubMed Central

Lee, Seongmu; Yen, Michael T.

2017-01-01

There has been an increased recognition for the role volume deflation plays in the aging periorbital area, and as such, rejuvenation strategies to augment and restore volume have developed and evolved. Hyaluronic acid fillers provide an efficient option for volume augmentation with good efficacy, longevity, and safety. An understanding of the changes in the upper and lower periocular area due to aging, the meticulous identification of focal hollows, and the precise delivery of filler to these areas can smooth contours and restore a rejuvenated periorbital area. PMID:28255285

Role of Lipid Metabolism in Plant Pollen Exine Development.

PubMed

Zhang, Dabing; Shi, Jianxin; Yang, Xijia

2016-01-01

Pollen plays important roles in the life cycle of angiosperms plants. It acts as not only a biological protector of male sperms but also a communicator between the male and the female reproductive organs, facilitating pollination and fertilization. Pollen is produced within the anther, and covered by the specialized outer envelope, pollen wall. Although the morphology of pollen varies among different plant species, the pollen wall is mainly comprised of three layers: the pollen coat, the outer exine layer, and the inner intine layer. Except the intine layer, the other two layers are basically of lipidic nature. Particularly, the outer pollen wall layer, the exine, is a highly resistant biopolymer of phenylpropanoid and lipidic monomers covalently coupled by ether and ester linkages. The precise molecular mechanisms underlying pollen coat formation and exine patterning remain largely elusive. Herein, we summarize the current genetic, phenotypic and biochemical studies regarding to the pollen exine development and underlying molecular regulatory mechanisms mainly obtained from monocot rice (Oryza sativa) and dicot Arabidopsis thaliana, aiming to extend our understandings of plant male reproductive biology. Genes, enzymes/proteins and regulatory factors that appear to play conserved and diversified roles in lipid biosynthesis, transportation and modification during pollen exine formation, were highlighted.

Brain-derived Neurotrophic Factor (BDNF)-TrkB Signaling in Inflammation-related Depression and Potential Therapeutic Targets

PubMed Central

Zhang, Ji-chun; Yao, Wei; Hashimoto, Kenji

2016-01-01

Depression is the most prevalent and among the most debilitating of psychiatric disorders. The precise neurobiology of this illness is unknown. Several lines of evidence suggest that peripheral and central inflammation plays a role in depressive symptoms, and that anti-inflammatory drugs can improve depressive symptoms in patients with inflammation-related depression. Signaling via brain-derived neurotrophic factor (BDNF) and its receptor, tropomycin receptor kinase B (TrkB) plays a key role in the pathophysiology of depression and in the therapeutic mechanisms of antidepressants. A recent paper showed that lipopolysaccharide (LPS)-induced inflammation gave rise to depression-like phenotype by altering BDNF-TrkB signaling in the prefrontal cortex, hippocampus, and nucleus accumbens, areas thought to be involved in the antidepressant effects of TrkB agonist, 7,8-dihydroxyflavone (7,8-DHF) and TrkB antagonist, ANA-12. Here we provide an overview of the tryptophan-kynurenine pathway and BDNF-TrkB signaling in the pathophysiology of inflammation-induced depression, and propose mechanistic actions for potential therapeutic agents. Additionally, the authors discuss the putative role of TrkB agonists and antagonists as novel therapeutic drugs for inflammation-related depression. PMID:26786147

Equal status in Ultimatum Games promotes rational sharing.

PubMed

Han, Xiao; Cao, Shinan; Bao, Jian-Zhang; Wang, Wen-Xu; Zhang, Boyu; Gao, Zi-You; Sánchez, Angel

2018-01-19

Experiments on the Ultimatum Game (UG) repeatedly show that people's behaviour is far from rational. In UG experiments, a subject proposes how to divide a pot and the other can accept or reject the proposal, in which case both lose everything. While rational people would offer and accept the minimum possible amount, in experiments low offers are often rejected and offers are typically larger than the minimum, and even fair. Several theoretical works have proposed that these results may arise evolutionarily when subjects act in both roles and there is a fixed interaction structure in the population specifying who plays with whom. We report the first experiments on structured UG with subjects playing simultaneously both roles. We observe that acceptance levels of responders approach rationality and proposers accommodate their offers to their environment. More precisely, subjects keep low acceptance levels all the time, but as proposers they follow a best-response-like approach to choose their offers. We thus find that status equality promotes rational sharing while the influence of structure leads to fairer offers compared to well-mixed populations. Our results are far from what is observed in single-role UG experiments and largely different from available predictions based on evolutionary game theory.

Darwinism and ethology. The role of natural selection in animals and humans.

PubMed

Gervet, J; Soleilhavoup, M

1997-11-01

The role of behaviour in biological evolution is examined within the context of Darwinism. All Darwinian models are based on the distinction of two mechanisms: one that permits faithful transmission of a feature from one generation to another, and another that differentially regulates the degree of this transmission. Behaviour plays a minimal role as an agent of transmission in the greater part of the animal kingdom; by contrast, the forms it may assume strongly influence the mechanisms of selection regulating the different rates of transmission. We consider the decisive feature of the human species to be the existence of a phenotypical system of cultural coding characterized by precision and reliability which are the distinctive feature of genetic coding in animals. We examine the consequences for the application of the Darwinian model to human history.

Atopic eczema and the filaggrin story.

PubMed

Brown, Sara J; Irvine, Alan D

2008-06-01

The discovery that null mutations in the filaggrin gene (FLG) are associated with atopic eczema represents the single most significant breakthrough in understanding the genetic basis of this complex disorder. The association has been replicated in multiple independent studies during the past 2 years with the use of various methodologies, from populations in Europe, the United States, and Japan. Filaggrin plays a key role in epidermal barrier function, and its association with atopic eczema emphasizes the importance of barrier dysfunction in eczema pathogenesis. This review aims to summarize the current state of knowledge regarding the role of FLG mutations in ichthyosis vulgaris, atopic eczema, and other skin disorders, with an emphasis on potential clinical applications. Further research is needed to clarify the precise role of filaggrin in skin and systemic atopic disease, to pave the way for novel therapeutic interventions.

NuSAP governs chromosome oscillation by facilitating the Kid-generated polar ejection force

PubMed Central

Li, Chenyu; Xue, Chenyi; Yang, Qiaoyun; Low, Boon Chuan; Liou, Yih-Cherng

2016-01-01

In vertebrate cells, chromosomes oscillate to align precisely during metaphase. NuSAP, a microtubule-associated protein, plays a critical role in stabilizing spindle microtubules. In this study, we utilize 3D time-lapse live-cell imaging to monitor the role of NuSAP in chromosome oscillation and identify NuSAP as a novel regulator of the chromokinesin, Kid. Depletion of NuSAP significantly suppresses the amplitude and velocity of chromosome oscillation. We analyse the effects of NuSAP and Kid depletion in monopolar and bipolar cells with or without kinetochore microtubule depletion. Twelve postulated conditions are deciphered to reveal the contribution of NuSAP to the polar force generated at kinetochore microtubules and to the regulation of the polar ejection force generated by Kid, thus revealing a pivotal role of NuSAP in chromosome oscillation. PMID:26839278

NuSAP governs chromosome oscillation by facilitating the Kid-generated polar ejection force.

PubMed

Li, Chenyu; Xue, Chenyi; Yang, Qiaoyun; Low, Boon Chuan; Liou, Yih-Cherng

2016-02-03

In vertebrate cells, chromosomes oscillate to align precisely during metaphase. NuSAP, a microtubule-associated protein, plays a critical role in stabilizing spindle microtubules. In this study, we utilize 3D time-lapse live-cell imaging to monitor the role of NuSAP in chromosome oscillation and identify NuSAP as a novel regulator of the chromokinesin, Kid. Depletion of NuSAP significantly suppresses the amplitude and velocity of chromosome oscillation. We analyse the effects of NuSAP and Kid depletion in monopolar and bipolar cells with or without kinetochore microtubule depletion. Twelve postulated conditions are deciphered to reveal the contribution of NuSAP to the polar force generated at kinetochore microtubules and to the regulation of the polar ejection force generated by Kid, thus revealing a pivotal role of NuSAP in chromosome oscillation.

The role of learning-related dopamine signals in addiction vulnerability.

PubMed

Huys, Quentin J M; Tobler, Philippe N; Hasler, Gregor; Flagel, Shelly B

2014-01-01

Dopaminergic signals play a mathematically precise role in reward-related learning, and variations in dopaminergic signaling have been implicated in vulnerability to addiction. Here, we provide a detailed overview of the relationship between theoretical, mathematical, and experimental accounts of phasic dopamine signaling, with implications for the role of learning-related dopamine signaling in addiction and related disorders. We describe the theoretical and behavioral characteristics of model-free learning based on errors in the prediction of reward, including step-by-step explanations of the underlying equations. We then use recent insights from an animal model that highlights individual variation in learning during a Pavlovian conditioning paradigm to describe overlapping aspects of incentive salience attribution and model-free learning. We argue that this provides a computationally coherent account of some features of addiction. © 2014 Elsevier B.V. All rights reserved.

Mechanobiology of Platelets: Techniques to Study the Role of Fluid Flow and Platelet Retraction Forces at the Micro- and Nano-Scale

PubMed Central

Feghhi, Shirin; Sniadecki, Nathan J.

2011-01-01

Coagulation involves a complex set of events that are important in maintaining hemostasis. Biochemical interactions are classically known to regulate the hemostatic process, but recent evidence has revealed that mechanical interactions between platelets and their surroundings can also play a substantial role. Investigations into platelet mechanobiology have been challenging however, due to the small dimensions of platelets and their glycoprotein receptors. Platelet researchers have recently turned to microfabricated devices to control these physical, nanometer-scale interactions with a higher degree of precision. These approaches have enabled exciting, new insights into the molecular and biomechanical factors that affect platelets in clot formation. In this review, we highlight the new tools used to understand platelet mechanobiology and the roles of adhesion, shear flow, and retraction forces in clot formation. PMID:22272117

Toward malaysian sustainable agriculture in 21st century

NASA Astrophysics Data System (ADS)

Khorramnia, K.; Shariff, A. R. M.; Rahim, A. Abdul; Mansor, S.

2014-02-01

Sustainable agriculture should be able to meet various social goals and objectives so that it can be maintained for an indefinite period without significant negative impacts on environment and natural resources. A wide variety of agricultural activities are running in Malaysia. Maintaining high quality of agricultural products with lower environmental impacts through a sustainable economic viability and life satisfaction of farmers and community are important factors helping to meet sustainable agriculture. Human resources are playing key role in directing the community toward sustainable development. The trend of improving the human development index in Malaysia is highest in the East Asia and the Pacific, high human development countries and the world, since 2000. Precision agriculture is providing strong tools to achieve sustainable agriculture. Different types of sensors, positioning and navigation systems, GIS, software and variable rate technology are well known components of precision agriculture. Drones and robots are promising tools that enabling farmers and managers to collect information or perform particular actions in remote areas or tough conditions. According to a survey, forestry and timber, rubber production and oil palm estates are three main agricultural divisions that precision agriculture may improve the productivity in respect to area of cropland/worker. Main factors affecting the adoption of precision agriculture in Malaysia are: a) Political and legal supports, b) Decision support systems and user interfaces c) Experienced research team works d) National educational policy e) Success in commercialization of precision agriculture system.

The Role of PKC-θ in CD4+ T Cells and HIV Infection: To the Nucleus and Back Again

PubMed Central

Phetsouphanh, Chansavath; Kelleher, Anthony D.

2015-01-01

Protein kinase C (PKC)-θ is the only member of the PKC family that has the ability to translocate to the immunological synapse between T cells and antigen-presenting cells upon T cell receptor and MHC-II recognition. PKC-θ interacts functionally and physically with other downstream effector molecules to mediate T cell activation, differentiation, and migration. It plays a critical role in the generation of Th2 and Th17 responses and is less important in Th1 and CTL responses. PKC-θ has been recently shown to play a role in the nucleus, where it mediates inducible gene expression in the development of memory CD4+ T cells. This novel PKC (nPKC) can up-regulate HIV-1 transcription and PKC-θ activators such as Prostratin have been used in early HIV-1 reservoir eradication studies. The exact manner of the activation of virus by these compounds and the role of PKC-θ, particularly its nuclear form and its association with NF-κB in both the cytoplasmic and nuclear compartments, needs further precise elucidation especially given the very important role of NF-κB in regulating transcription from the integrated retrovirus. Continued studies of this nPKC isoform will give further insight into the complexity of T cell signaling kinases. PMID:26284074

The Brain’s Default Network and its Adaptive Role in Internal Mentation

PubMed Central

Andrews-Hanna, Jessica R.

2013-01-01

During the many idle moments that comprise daily life, the human brain increases its activity across a set of midline and lateral cortical brain regions known as the “default network.” Despite the robustness with which the brain defaults to this pattern of activity, surprisingly little is known about the network’s precise anatomical organization and adaptive functions. To provide insight into these questions, this article synthesizes recent literature from structural and functional imaging with a growing behavioral literature on mind wandering. Results characterize the default network as a set of interacting hubs and subsystems that play an important role in “internal mentation” – the introspective and adaptive mental activities in which humans spontaneously and deliberately engage in everyday. . PMID:21677128

Biomimetic approaches to control soluble concentration gradients in biomaterials.

PubMed

Nguyen, Eric H; Schwartz, Michael P; Murphy, William L

2011-04-08

Soluble concentration gradients play a critical role in controlling tissue formation during embryonic development. The importance of soluble signaling in biology has motivated engineers to design systems that allow precise and quantitative manipulation of gradient formation in vitro. Engineering techniques have increasingly moved to the third dimension in order to provide more physiologically relevant models to study the biological role of gradient formation and to guide strategies for controlling new tissue formation for therapeutic applications. This review provides an overview of efforts to design biomimetic strategies for soluble gradient formation, with a focus on microfluidic techniques and biomaterials approaches for moving gradient generation to the third dimension. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Potential role of retinoids in ovarian physiology and pathogenesis of polycystic ovary syndrome.

PubMed

Jiang, Yanwen; Li, Chunjin; Chen, Lu; Wang, Fengge; Zhou, Xu

2017-06-01

Retinoids (retinol and its derivatives) are required for maintaining vision, immunity, barrier function, reproduction, embryogenesis, cell proliferation and differentiation. Furthermore, retinoid signaling plays a key role in initiating meiosis of germ cells of the mammalian fetal ovary. Recently, studies indicated that precise retinoid level regulation in the ovary provides a molecular control of ovarian development, steroidogenesis and oocyte maturation. Besides, abnormal retinoid signaling may be involved in the pathogenesis of polycystic ovary syndrome (PCOS), one of the most common ovarian endocrinopathies in reproductive-aged women worldwide. This review primarily summarizes recent advancements made in investigating the action of retinoid signaling in ovarian physiology as well as the abnormal retinoid signaling in PCOS. Copyright © 2017. Published by Elsevier B.V.

The biology and function of exosomes in cancer.

PubMed

Kalluri, Raghu

2016-04-01

Humans circulate quadrillions of exosomes at all times. Exosomes are a class of extracellular vesicles released by all cells, with a size range of 40-150 nm and a lipid bilayer membrane. Exosomes contain DNA, RNA, and proteins. Exosomes likely remove excess and/or unnecessary constituents from the cells, functioning like garbage bags, although their precise physiological role remains unknown. Additionally, exosomes may mediate specific cell-to-cell communication and activate signaling pathways in cells they fuse or interact with. Exosomes are detected in the tumor microenvironment, and emerging evidence suggests that they play a role in facilitating tumorigenesis by regulating angiogenesis, immunity, and metastasis. Circulating exosomes can be used as liquid biopsies and noninvasive biomarkers for early detection, diagnosis, and treatment of cancer patients.

A pilot study of children's physical activity levels during imagination-based mobile games.

PubMed

Patten, James W; Iarocci, Grace; Bojin, Nis

2017-09-01

This research looked at Biba: a suite of mobile games intended to get kids back out to playgrounds and engaging in more moderate to vigorous physical activity (MVPA). Year after year, annual national surveys report a general decline in physical activity amongst children and a corresponding increase in screen time. Further to this, time spent outside by children has been reported to be on the decline since the 1980s. Recent work has suggested that in order to 'maintain the outdoor recreation participation of children across America, park and recreation professionals may need to embrace the expanding role of technology'. This research tested Biba in precisely this regard, deploying a 20-subject within-subject experimental design that compared Biba playground gameplay with typical free play playground sessions, measuring heart rate activity in them. The outcome demonstrated that Biba playground play results in greater amounts of MVPA with a difference in heart rate that was significantly higher in the Biba play session than in the free play session t(19) = 2.41, p < 0.05.

Skilful force control in expert pianists.

PubMed

Oku, Takanori; Furuya, Shinichi

2017-05-01

Dexterous object manipulation in skilful behaviours such as surgery, craft making, and musical performance involves fast, precise, and efficient control of force with the fingers. A challenge in playing musical instruments is the requirement of independent control of the magnitude and rate of force production, which typically vary in relation to loudness and tempo. However, it is unknown how expert musicians skilfully control finger force to elicit tones with a wide range of loudness and tempi. Here, we addressed this issue by comparing the variation of spatiotemporal characteristics of force during repetitive and simultaneous piano keystrokes in relation to the loudness and tempo between pianists and musically untrained individuals. While the peak key-descending velocity varied with loudness but not with tempo in both groups, the peak and impulse of the key-depressing force were smaller in pianists than in the non-musicians, specifically when eliciting loud tones, suggesting superior energetic efficiency in the trained individuals. The key-depressing force was more consistent across strikes in pianists than in the non-musicians at all loudness levels but only at slow tempi, confirming expertise-dependency of precise force control. A regression analysis demonstrated that individual differences in the keystroke rates when playing at the fastest tempo across the trained pianists were negatively associated with the force impulse during the key depression but not with the peak force only at the loudest tone. This suggests that rapid reductions of force following the key depression plays a role in considerably fast performance of repetitive piano keystrokes.

Semantic Health Knowledge Graph: Semantic Integration of Heterogeneous Medical Knowledge and Services.

PubMed

Shi, Longxiang; Li, Shijian; Yang, Xiaoran; Qi, Jiaheng; Pan, Gang; Zhou, Binbin

2017-01-01

With the explosion of healthcare information, there has been a tremendous amount of heterogeneous textual medical knowledge (TMK), which plays an essential role in healthcare information systems. Existing works for integrating and utilizing the TMK mainly focus on straightforward connections establishment and pay less attention to make computers interpret and retrieve knowledge correctly and quickly. In this paper, we explore a novel model to organize and integrate the TMK into conceptual graphs. We then employ a framework to automatically retrieve knowledge in knowledge graphs with a high precision. In order to perform reasonable inference on knowledge graphs, we propose a contextual inference pruning algorithm to achieve efficient chain inference. Our algorithm achieves a better inference result with precision and recall of 92% and 96%, respectively, which can avoid most of the meaningless inferences. In addition, we implement two prototypes and provide services, and the results show our approach is practical and effective.

Semantic Health Knowledge Graph: Semantic Integration of Heterogeneous Medical Knowledge and Services

PubMed Central

Yang, Xiaoran; Qi, Jiaheng; Pan, Gang; Zhou, Binbin

2017-01-01

With the explosion of healthcare information, there has been a tremendous amount of heterogeneous textual medical knowledge (TMK), which plays an essential role in healthcare information systems. Existing works for integrating and utilizing the TMK mainly focus on straightforward connections establishment and pay less attention to make computers interpret and retrieve knowledge correctly and quickly. In this paper, we explore a novel model to organize and integrate the TMK into conceptual graphs. We then employ a framework to automatically retrieve knowledge in knowledge graphs with a high precision. In order to perform reasonable inference on knowledge graphs, we propose a contextual inference pruning algorithm to achieve efficient chain inference. Our algorithm achieves a better inference result with precision and recall of 92% and 96%, respectively, which can avoid most of the meaningless inferences. In addition, we implement two prototypes and provide services, and the results show our approach is practical and effective. PMID:28299322

Vehicle parts detection based on Faster - RCNN with location constraints of vehicle parts feature point

NASA Astrophysics Data System (ADS)

Yang, Liqin; Sang, Nong; Gao, Changxin

2018-03-01

Vehicle parts detection plays an important role in public transportation safety and mobility. The detection of vehicle parts is to detect the position of each vehicle part. We propose a new approach by combining Faster RCNN and three level cascaded convolutional neural network (DCNN). The output of Faster RCNN is a series of bounding boxes with coordinate information, from which we can locate vehicle parts. DCNN can precisely predict feature point position, which is the center of vehicle part. We design an output strategy by combining these two results. There are two advantages for this. The quality of the bounding boxes are greatly improved, which means vehicle parts feature point position can be located more precise. Meanwhile we preserve the position relationship between vehicle parts and effectively improve the validity and reliability of the result. By using our algorithm, the performance of the vehicle parts detection improve obviously compared with Faster RCNN.

Correlation measurements in nuclear {beta}-decay using traps and polarized low energy beams

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

Naviliat-Cuncic, Oscar

2013-05-06

Precision measurements in nuclear {beta}-decay provide sensitive means to test discrete symmetries in the weak interaction and to determine some of the fundamental constants in semi-leptonic decays, like the coupling of the lightest quarks to charged weak bosons. The main motivation of such measurements is to find deviations from Standard Model predictions as possible indications of new physics. In this contribution I will focus on two topics related to precision measurements in nuclear {beta}-decay: i) the determination of the V{sub ud} element of the Cabibbo-Kobayashi-Maskawa quark mixing matrix from nuclear mirror transitions and ii) the search for exotic scalar ormore » tensor contributions from {beta}{nu} angular correlations. The purpose is to underline the role being played by experimental techniques based on the confinement of radioactive species with atom and ion traps as well as the plans to use low energy polarized beams.« less

Simultaneous Enhancements of Conductivity and Stability for Anion Exchange Membranes (AEMs) through Precise Structure Design

PubMed Central

Ran, Jin; Wu, Liang; Wei, Bing; Chen, Yaoyao; Xu, Tongwen

2014-01-01

Polymeric materials as anion exchange membranes (AEMs) play an essential role in the field of energy and environment. The achievement of high performance AEMs by the precise manipulation of macromolecular architecture remains a daunting challenge. Herein, we firstly report a novel rod-coil graft copolymer AEM, possessing rigid hydrophobic main chains and soft hydrophilic graft chains. The low graft density, which can alleviate the adverse influences of ioinc graft chains on the main chains, was obtained by using the living polymerization technique. Consequently, the grafted ionic groups which result in the degradation of polymer backbone was decreased to a small degree. Moreover, the relatively long graft chains induced the nanophase separation between the hydrophobic polymer chains and hydrophilic graft chains, which creates a convinient pathway for high hydroxide ion mobility. Such an accurate molecular design simultaneously improves the hydroxide ion conductivity and alkaline stability as well as dimensional stability. PMID:25255843

Recognition Imaging of Acetylated Chromatin Using a DNA Aptamer

PubMed Central

Lin, Liyun; Fu, Qiang; Williams, Berea A.R.; Azzaz, Abdelhamid M.; Shogren-Knaak, Michael A.; Chaput, John C.; Lindsay, Stuart

2009-01-01

Histone acetylation plays an important role in the regulation of gene expression. A DNA aptamer generated by in vitro selection to be highly specific for histone H4 protein acetylated at lysine 16 was used as a recognition element for atomic force microscopy-based recognition imaging of synthetic nucleosomal arrays with precisely controlled acetylation. The aptamer proved to be reasonably specific at recognizing acetylated histones, with recognition efficiencies of 60% on-target and 12% off-target. Though this selectivity is much poorer than the >2000:1 equilibrium specificity of the aptamer, it is a large improvement on the performance of a ChIP-quality antibody, which is not selective at all in this application, and it should permit high-fidelity recognition with repeated imaging. The ability to image the precise location of posttranslational modifications may permit nanometer-scale investigation of their effect on chromatin structure. PMID:19751687

Research on carrying capacity of hydrostatic slideway on heavy-duty gantry CNC machine

NASA Astrophysics Data System (ADS)

Cui, Chao; Guo, Tieneng; Wang, Yijie; Dai, Qin

2017-05-01

Hydrostatic slideway is a key part in the heavy-duty gantry CNC machine, which supports the total weight of the gantry and moves smoothly along the table. Therefore, the oil film between sliding rails plays an important role on the carrying capacity and precision of machine. In this paper, the oil film in no friction is simulated with three-dimensional CFD. The carrying capacity of heavy hydrostatic slideway, pressure and velocity characteristic of the flow field are analyzed. The simulation result is verified through comparing with the experimental data obtained from the heavy-duty gantry machine. For the requirement of engineering, the oil film carrying capacity is analyzed with simplified theoretical method. The precision of the simplified method is evaluated and the effectiveness is verified with the experimental data. The simplified calculation method is provided for designing oil pad on heavy-duty gantry CNC machine hydrostatic slideway.

Simultaneous Enhancements of Conductivity and Stability for Anion Exchange Membranes (AEMs) through Precise Structure Design

NASA Astrophysics Data System (ADS)

Ran, Jin; Wu, Liang; Wei, Bing; Chen, Yaoyao; Xu, Tongwen

2014-09-01

Polymeric materials as anion exchange membranes (AEMs) play an essential role in the field of energy and environment. The achievement of high performance AEMs by the precise manipulation of macromolecular architecture remains a daunting challenge. Herein, we firstly report a novel rod-coil graft copolymer AEM, possessing rigid hydrophobic main chains and soft hydrophilic graft chains. The low graft density, which can alleviate the adverse influences of ioinc graft chains on the main chains, was obtained by using the living polymerization technique. Consequently, the grafted ionic groups which result in the degradation of polymer backbone was decreased to a small degree. Moreover, the relatively long graft chains induced the nanophase separation between the hydrophobic polymer chains and hydrophilic graft chains, which creates a convinient pathway for high hydroxide ion mobility. Such an accurate molecular design simultaneously improves the hydroxide ion conductivity and alkaline stability as well as dimensional stability.

Pose measurement method and experiments for high-speed rolling targets in a wind tunnel.

PubMed

Jia, Zhenyuan; Ma, Xin; Liu, Wei; Lu, Wenbo; Li, Xiao; Chen, Ling; Wang, Zhengqu; Cui, Xiaochun

2014-12-12

High-precision wind tunnel simulation tests play an important role in aircraft design and manufacture. In this study, a high-speed pose vision measurement method is proposed for high-speed and rolling targets in a supersonic wind tunnel. To obtain images with high signal-to-noise ratio and avoid impacts on the aerodynamic shape of the rolling targets, a high-speed image acquisition method based on ultrathin retro-reflection markers is presented. Since markers are small-sized and some of them may be lost when the target is rolling, a novel markers layout with which markers are distributed evenly on the surface is proposed based on a spatial coding method to achieve highly accurate pose information. Additionally, a pose acquisition is carried out according to the mentioned markers layout after removing mismatching points by Case Deletion Diagnostics. Finally, experiments on measuring the pose parameters of high-speed targets in the laboratory and in a supersonic wind tunnel are conducted to verify the feasibility and effectiveness of the proposed method. Experimental results indicate that the position measurement precision is less than 0.16 mm, the pitching and yaw angle precision less than 0.132° and the roll angle precision 0.712°.

Pose Measurement Method and Experiments for High-Speed Rolling Targets in a Wind Tunnel

PubMed Central

Jia, Zhenyuan; Ma, Xin; Liu, Wei; Lu, Wenbo; Li, Xiao; Chen, Ling; Wang, Zhengqu; Cui, Xiaochun

2014-01-01

High-precision wind tunnel simulation tests play an important role in aircraft design and manufacture. In this study, a high-speed pose vision measurement method is proposed for high-speed and rolling targets in a supersonic wind tunnel. To obtain images with high signal-to-noise ratio and avoid impacts on the aerodynamic shape of the rolling targets, a high-speed image acquisition method based on ultrathin retro-reflection markers is presented. Since markers are small-sized and some of them may be lost when the target is rolling, a novel markers layout with which markers are distributed evenly on the surface is proposed based on a spatial coding method to achieve highly accurate pose information. Additionally, a pose acquisition is carried out according to the mentioned markers layout after removing mismatching points by Case Deletion Diagnostics. Finally, experiments on measuring the pose parameters of high-speed targets in the laboratory and in a supersonic wind tunnel are conducted to verify the feasibility and effectiveness of the proposed method. Experimental results indicate that the position measurement precision is less than 0.16 mm, the pitching and yaw angle precision less than 0.132° and the roll angle precision 0.712°. PMID:25615732

Error analysis of high-rate GNSS precise point positioning for seismic wave measurement

NASA Astrophysics Data System (ADS)

Shu, Yuanming; Shi, Yun; Xu, Peiliang; Niu, Xiaoji; Liu, Jingnan

2017-06-01

High-rate GNSS precise point positioning (PPP) has been playing a more and more important role in providing precise positioning information in fast time-varying environments. Although kinematic PPP is commonly known to have a precision of a few centimeters, the precision of high-rate PPP within a short period of time has been reported recently with experiments to reach a few millimeters in the horizontal components and sub-centimeters in the vertical component to measure seismic motion, which is several times better than the conventional kinematic PPP practice. To fully understand the mechanism of mystified excellent performance of high-rate PPP within a short period of time, we have carried out a theoretical error analysis of PPP and conducted the corresponding simulations within a short period of time. The theoretical analysis has clearly indicated that the high-rate PPP errors consist of two types: the residual systematic errors at the starting epoch, which affect high-rate PPP through the change of satellite geometry, and the time-varying systematic errors between the starting epoch and the current epoch. Both the theoretical error analysis and simulated results are fully consistent with and thus have unambiguously confirmed the reported high precision of high-rate PPP, which has been further affirmed here by the real data experiments, indicating that high-rate PPP can indeed achieve the millimeter level of precision in the horizontal components and the sub-centimeter level of precision in the vertical component to measure motion within a short period of time. The simulation results have clearly shown that the random noise of carrier phases and higher order ionospheric errors are two major factors to affect the precision of high-rate PPP within a short period of time. The experiments with real data have also indicated that the precision of PPP solutions can degrade to the cm level in both the horizontal and vertical components, if the geometry of satellites is rather poor with a large DOP value.

Opera and neuroscience.

PubMed

Lorusso, Lorenzo; Franchini, Antonia Francesca; Porro, Alessandro

2015-01-01

Opera is the most complete form of theatrical representation, characterized by musical accompaniment, both instrumental and vocal. It has played an important role in sociocultural spheres, affecting the various social strata and reflecting customs and ideas in different centuries. Composers have created pieces that have also shown the development of medicine. Since the birth of opera in seventeenth century in Italy, neuroscience has played an important role in influencing the representation of madness and neurological aspects. From the Folly of the Renaissance, a path toward a representation of madness was developed, initially linked to the myths of classical antiquity. In the seventeenth and eighteenth centuries, madness was represented as comical or funny, of a loving nature and influenced by the spread of the Commedia dell'Arte (Comedy of Art). In the nineteenth century, with the rise of the first scientific theories of the mind, insanity took more precise connotations and was separated from other psychiatric and neurological diseases. The operas of the twentieth century depicted psychiatric and neurological diseases, taking into account newer medical and scientific discoveries. © 2015 Elsevier B.V. All rights reserved.

Functional hypothalamic amenorrhea: current view on neuroendocrine aberrations.

PubMed

Meczekalski, Blazej; Podfigurna-Stopa, Agnieszka; Warenik-Szymankiewicz, Alina; Genazzani, Andrea Riccardo

2008-01-01

Functional hypothalamic amenorrhea (FHA) is defined as a non-organic and reversible disorder in which the impairment of gonadotropin-releasing hormone (GnRH) pulsatile secretion plays a key role. There are main three types of FHA: stress-related amenorrhea, weight loss-related amenorrhea and exercise-related amenorrhea. The spectrum of GnRH-luteinizing hormone (LH) disturbances in FHA is very broad and includes lower mean frequency of LH pulses, complete absence of LH pulsatility, normal-appearing secretion pattern and higher mean frequency of LH pulses. Precise mechanisms underlying the pathophysiology of FHA are very complex and unclear. Numerous neuropeptides, neurotransmitters and neurosteroids play important roles in the physiological regulation of GnRH pulsatile secretion and there is evidence that different neuropeptides may be involved in the pathophysiology of FHA. Particular attention is paid to such substances as allopregnanolone, neuropeptide Y, corticotropin-releasing hormone, leptin, ghrelin and beta-endorphin. Some studies reveal significant changes in these mentioned substances in patients with FHA. There are also speculations about use some of these substances or their antagonists in the treatment of FHA.

Characteristics for electrochemical machining with nanoscale voltage pulses.

PubMed

Lee, E S; Back, S Y; Lee, J T

2009-06-01

Electrochemical machining has traditionally been used in highly specialized fields, such as those of the aerospace and defense industries. It is now increasingly being applied in other industries, where parts with difficult-to-cut material, complex geometry and tribology, and devices of nanoscale and microscale are required. Electric characteristic plays a principal function role in and chemical characteristic plays an assistant function role in electrochemical machining. Therefore, essential parameters in electrochemical machining can be described current density, machining time, inter-electrode gap size, electrolyte, electrode shape etc. Electrochemical machining provides an economical and effective method for machining high strength, high tension and heat-resistant materials into complex shapes such as turbine blades of titanium and aluminum alloys. The application of nanoscale voltage pulses between a tool electrode and a workpiece in an electrochemical environment allows the three-dimensional machining of conducting materials with sub-micrometer precision. In this study, micro probe are developed by electrochemical etching and micro holes are manufactured using these micro probe as tool electrodes. Micro holes and microgroove can be accurately achieved by using nanoscale voltages pulses.

mRNA Traffic Control Reviewed: N6-Methyladenosine (m6 A) Takes the Driver's Seat.

PubMed

Visvanathan, Abhirami; Somasundaram, Kumaravel

2018-01-01

Messenger RNA is a flexible tool box that plays a key role in the dynamic regulation of gene expression. RNA modifications variegate the message conveyed by the mRNA. Similar to DNA and histone modifications, mRNA modifications are reversible and play a key role in the regulation of molecular events. Our understanding about the landscape of RNA modifications is still rudimentary in contrast to DNA and histone modifications. The major obstacle has been the lack of sensitive detection methods since they are non-editing events. However, with the advent of next-generation sequencing techniques, RNA modifications are being identified precisely at single nucleotide resolution. In recent years, methylation at the N6 position of adenine (m 6 A) has gained the attention of RNA biologists. The m 6 A modification has a set of writers (methylases), erasers (demethylases), and readers. Here, we provide a summary of interesting facts, conflicting findings, and recent advances in the technical and functional aspects of the m 6 A epitranscriptome. © 2017 WILEY Periodicals, Inc.

Necroptosis in neurodegenerative diseases: a potential therapeutic target

PubMed Central

Zhang, Shuo; Tang, Mi-bo; Luo, Hai-yang; Shi, Chang-he; Xu, Yu-ming

2017-01-01

Neurodegenerative diseases are a group of chronic progressive disorders characterized by neuronal loss. Necroptosis, a recently discovered form of programmed cell death, is a cell death mechanism that has necrosis-like morphological characteristics. Necroptosis activation relies on the receptor-interacting protein (RIP) homology interaction motif (RHIM). A variety of RHIM-containing proteins transduce necroptotic signals from the cell trigger to the cell death mediators RIP3 and mixed lineage kinase domain-like protein (MLKL). RIP1 plays a particularly important and complex role in necroptotic cell death regulation ranging from cell death activation to inhibition, and these functions are often cell type and context dependent. Increasing evidence suggests that necroptosis plays an important role in the pathogenesis of neurodegenerative diseases. Moreover, small molecules such as necrostatin-1 are thought inhibit necroptotic signaling pathway. Understanding the precise mechanisms underlying necroptosis and its interactions with other cell death pathways in neurodegenerative diseases could provide significant therapeutic insights. The present review is aimed at summarizing the molecular mechanisms of necroptosis and highlighting the emerging evidence on necroptosis as a major driver of neuron cell death in neurodegenerative diseases. PMID:28661482

A serine proteinase homologue, SPH-3, plays a central role in insect immunity.

PubMed

Felföldi, Gabriella; Eleftherianos, Ioannis; Ffrench-Constant, Richard H; Venekei, István

2011-04-15

Numerous vertebrate and invertebrate genes encode serine proteinase homologues (SPHs) similar to members of the serine proteinase family, but lacking one or more residues of the catalytic triad. These SPH proteins are thought to play a role in immunity, but their precise functions are poorly understood. In this study, we show that SPH-3 (an insect non-clip domain-containing SPH) is of central importance in the immune response of a model lepidopteran, Manduca sexta. We examine M. sexta infection with a virulent, insect-specific, Gram-negative bacterium Photorhabdus luminescens. RNA interference suppression of bacteria-induced SPH-3 synthesis severely compromises the insect's ability to defend itself against infection by preventing the transcription of multiple antimicrobial effector genes, but, surprisingly, not the transcription of immune recognition genes. Upregulation of the gene encoding prophenoloxidase and the activity of the phenoloxidase enzyme are among the antimicrobial responses that are severely attenuated on SPH-3 knockdown. These findings suggest the existence of two largely independent signaling pathways controlling immune recognition by the fat body, one governing effector gene transcription, and the other regulating genes encoding pattern recognition proteins.

Noise-induced hearing loss increases the temporal precision of complex envelope coding by auditory-nerve fibers

PubMed Central

Henry, Kenneth S.; Kale, Sushrut; Heinz, Michael G.

2014-01-01

While changes in cochlear frequency tuning are thought to play an important role in the perceptual difficulties of people with sensorineural hearing loss (SNHL), the possible role of temporal processing deficits remains less clear. Our knowledge of temporal envelope coding in the impaired cochlea is limited to two studies that examined auditory-nerve fiber responses to narrowband amplitude modulated stimuli. In the present study, we used Wiener-kernel analyses of auditory-nerve fiber responses to broadband Gaussian noise in anesthetized chinchillas to quantify changes in temporal envelope coding with noise-induced SNHL. Temporal modulation transfer functions (TMTFs) and temporal windows of sensitivity to acoustic stimulation were computed from 2nd-order Wiener kernels and analyzed to estimate the temporal precision, amplitude, and latency of envelope coding. Noise overexposure was associated with slower (less negative) TMTF roll-off with increasing modulation frequency and reduced temporal window duration. The results show that at equal stimulus sensation level, SNHL increases the temporal precision of envelope coding by 20–30%. Furthermore, SNHL increased the amplitude of envelope coding by 50% in fibers with CFs from 1–2 kHz and decreased mean response latency by 0.4 ms. While a previous study of envelope coding demonstrated a similar increase in response amplitude, the present study is the first to show enhanced temporal precision. This new finding may relate to the use of a more complex stimulus with broad frequency bandwidth and a dynamic temporal envelope. Exaggerated neural coding of fast envelope modulations may contribute to perceptual difficulties in people with SNHL by acting as a distraction from more relevant acoustic cues, especially in fluctuating background noise. Finally, the results underscore the value of studying sensory systems with more natural, real-world stimuli. PMID:24596545

Mechanisms of bone remodeling: implications for clinical practice.

PubMed

Kenny, Anne M; Raisz, Lawrence G

2002-01-01

The adult skeleton undergoes continuous remodeling. The remodeling cycle involves the interaction of cells of osteoblastic and osteoclastic lineage and is regulated by both systemic hormones and local factors. In addition to the systemic calcium-regulating hormones, parathyroid hormone, 1,25-dihydroxy vitamin D and calcitonin, sex hormones play an important role. Estrogen has been identified as the major inhibitor of bone resorption in both men and women. Androgen is important not only as a source of estrogen, through the action of aromatase, but also for its direct effect in stimulating bone formation. The effects of sex hormones may be mediated by their ability to alter the secretion of local cytokines, prostaglandins and growth factors. Sex hormone action is also modulated by the level of sex hormone-binding globulin in the circulation. A more precise analysis of these effects has been made possible by the development of new methods of measuring not only bone mineral density, but also relative rates of bone formation and resorption using biochemical markers. These new approaches have allowed us to define more precisely the specific roles of androgens, estrogens and other regulatory hormones in human skeletal physiology and pathophysiology.

Fluorescence anisotropy (polarization): from drug screening to precision medicine

PubMed Central

Zhang, Hairong; Wu, Qian; Berezin, Mikhail Y.

2016-01-01

Introduction Fluorescence anisotropy (FA) is one of the major established methods accepted by industry and regulatory agencies for understanding the mechanisms of drug action and selecting drug candidates utilizing a high-throughput format. Areas covered This review covers the basics of FA and complementary methods, such as fluorescence lifetime anisotropy and their roles in the drug discovery process. The authors highlight the factors affecting FA readouts, fluorophore selection, and instrumentation. Furthermore, the authors describe the recent development of a successful, commercially valuable FA assay for Long QT syndrome drug toxicity to illustrate the role that FA can play in the early stages of drug discovery. Expert opinion Despite the success in drug discovery, the FA-based technique experiences competitive pressure from other homogeneous assays. That being said, FA is an established yet rapidly developing technique, recognized by academic institutions, the pharmaceutical industry, and regulatory agencies across the globe. The technical problems encountered in working with small molecules in homogeneous assays are largely solved, and new challenges come from more complex biological molecules and nanoparticles. With that, FA will remain one of the major work-horse techniques leading to precision (personalized) medicine. PMID:26289575

[Ghrelin: a gastric hormone at the crossroad between growth and appetite regulation].

PubMed

Labarthe, Alexandra; Tolle, Virginie

2016-01-01

Ghrelin is a 28 amino acid peptide hormone synthesized within the gastrointestinal tract. Initially identified as the endogenous ligand of the GHS-R1a (Growth Hormone Secretagogue Receptor 1a), ghrelin is a powerful stimulator of growth hormone (GH) secretion. At the crossroad between nutrition, growth and long-term energy metabolism, ghrelin also plays a unique role as the first identified gastric hormone increasing appetite and adiposity. However, the role of the ghrelin/GHS-R system in the physiology of growth, feeding behaviour and energy homeostasis needs to be better understood. Utilization of pharmacological tools and complementary animal models with deficiency in preproghrelin, ghrelin-O-acyl-transferase (GOAT - the enzyme that acylates ghrelin -) or GHS-R in situations of chronic undernutrition or high fat diet gives a more precise overview of the role of ghrelin in the pathophysiology of eating and metabolic disorders. © Société de Biologie, 2017.

Emerging Mechanisms of Innate Immunity and Their Translational Potential in Inflammatory Bowel Disease

PubMed Central

Corridoni, Daniele; Chapman, Thomas; Ambrose, Tim; Simmons, Alison

2018-01-01

Activation of the innate immune system through pattern-recognition receptor (PRR) signaling plays a pivotal role in the early induction of host defense following exposure to pathogens. Loss of intestinal innate immune regulation leading aberrant immune responses has been implicated in the pathogenesis of inflammatory bowel disease (IBD). The precise role of PRRs in gut inflammation is not well understood, but considering their role as bacterial sensors and their genetic association with IBD, they likely contribute to dysregulated immune responses to the commensal microbiota. The purpose of this review is to evaluate the emerging functions of PRRs including their functional cross-talk, how they respond to mitochondrial damage, induce mitophagy or autophagy, and influence adaptive immune responses by interacting with the antigen presentation machinery. The review also summarizes some of the recent attempts to harness these pathways for therapeutic approaches in intestinal inflammation. PMID:29515999

Analysing playing using the note-time playing path.

PubMed

de Graaff, Deborah L E; Schubert, Emery

2011-03-01

This article introduces a new method of data analysis that represents the playing of written music as a graph. The method, inspired by Miklaszewski, charts low-level note timings from a sound recording of a single-line instrument using high-precision audio-to-MIDI conversion software. Note onset times of pitch sequences are then plotted against the score-predicted timings to produce a Note-Time Playing Path (NTPP). The score-predicted onset time of each sequentially performed note (horizontal axis) unfolds in performed time down the page (vertical axis). NTPPs provide a visualisation that shows (1) tempo variations, (2) repetitive practice behaviours, (3) segmenting of material, (4) precise note time positions, and (5) time spent on playing or not playing. The NTPP can provide significant new insights into behaviour and cognition of music performance and may also be used to complement established traditional approaches such as think-alouds, interviews, and video coding.

The current status and problems confronted in delivering precision medicine in Japan and Europe.

PubMed

Bando, Hideaki

Precision medicine has been defined as "a predictive, preventive, personalized, and participatory health care service delivery model." Today, developments in next-generation sequencing and information technology have made precision medicine possible, with massive amounts of genetic, "omics," clinical, environmental, and lifestyle data now available. Unfortunately, differences in governmental support and health care regulations have resulted in heterogeneous progress among countries. In Japan, for example, precision cancer screening and treatments are increasingly being promoted, with collaboration among research, governmental, and pharmaceutical agencies taking place in the nationwide SCRUM-Japan cancer genome screening project. The missions of SCRUM-Japan are to deliver the most appropriate therapeutic agents to the most suitable patients, and to play key roles in the development of multiplex diagnostic products and new indications for targeted therapy. Starting in February 2015 and ending in March 2017, the aim is to enroll 4750 patients with cancer (2350 patients with lung cancer and 2400 patients with gastrointestinal tract cancer). Compared with other developed countries, investments in scientific innovation for biomedical and omics research are matched or even surpassed in Europe, but regulatory differences in each countries are a major hurdle to rapid implementation. Although market approval for pharmaceuticals is centralized through the European Medicines Agency, access to health care is heterogeneously regulated at national levels, which undermines the consistency, comparability, and quality of precision medicine for cancer patients in Europe. In this review, we focus on the current progress of precision medicine in Japan and Europe, and clarify the differences in progress and the hurdles faced moving forward. Copyright © 2017 Elsevier Inc. All rights reserved.

How cells handle cholesterol.

PubMed

Simons, K; Ikonen, E

2000-12-01

Cholesterol plays an indispensable role in regulating the properties of cell membranes in mammalian cells. Recent advances suggest that cholesterol exerts many of its actions mainly by maintaining sphingolipid rafts in a functional state. How rafts contribute to cholesterol metabolism and transport in the cell is still an open issue. It has long been known that cellular cholesterol levels are precisely controlled by biosynthesis, efflux from cells, and influx of lipoprotein cholesterol into cells. The regulation of cholesterol homeostasis is now receiving a new focus, and this changed perspective may throw light on diseases caused by cholesterol excess, the prime example being atherosclerosis.

Optimization of process parameters in welding of dissimilar steels using robot TIG welding

NASA Astrophysics Data System (ADS)

Navaneeswar Reddy, G.; VenkataRamana, M.

2018-03-01

Robot TIG welding is a modern technique used for joining two work pieces with high precision. Design of Experiments is used to conduct experiments by varying weld parameters like current, wire feed and travelling speed. The welding parameters play important role in joining of dissimilar stainless steel SS 304L and SS430. In this work, influences of welding parameter on Robot TIG Welded specimens are investigated using Response Surface Methodology. The Micro Vickers hardness tests of the weldments are measured. The process parameters are optimized to maximize the hardness of the weldments.

Data-Driven Healthcare: Challenges and Opportunities for Interactive Visualization.

PubMed

Gotz, David; Borland, David

2016-01-01

The healthcare industry's widespread digitization efforts are reshaping one of the largest sectors of the world's economy. This transformation is enabling systems that promise to use ever-improving data-driven evidence to help doctors make more precise diagnoses, institutions identify at risk patients for intervention, clinicians develop more personalized treatment plans, and researchers better understand medical outcomes within complex patient populations. Given the scale and complexity of the data required to achieve these goals, advanced data visualization tools have the potential to play a critical role. This article reviews a number of visualization challenges unique to the healthcare discipline.

Laser micro-etching of metal prostheses for personal identification

PubMed Central

Ganapathy, Dhanraj; Sivaswamy, Vinay; Sekhar, Prathap

2017-01-01

Denture marking techniques play a vital role in establishing personal identification in suitable clinical and forensic situations. The denture marking techniques are categorized broadly into additive and ablative methods. Additive methods involve embedding or impregnation of markers for establishing personal identity. Ablative methods involve partial removal of the denture surface thereby providing a marking for identification. Engraving and etching methods are the commonly used ablative methods. Ablative methods can be of contact and noncontact subtypes. Laser micro-etching is a precise noncontact ablative denture marking technique that could be used for prostheses-guided personal identification. PMID:28584473

Laser micro-etching of metal prostheses for personal identification.

PubMed

Ganapathy, Dhanraj; Sivaswamy, Vinay; Sekhar, Prathap

2017-01-01

Denture marking techniques play a vital role in establishing personal identification in suitable clinical and forensic situations. The denture marking techniques are categorized broadly into additive and ablative methods. Additive methods involve embedding or impregnation of markers for establishing personal identity. Ablative methods involve partial removal of the denture surface thereby providing a marking for identification. Engraving and etching methods are the commonly used ablative methods. Ablative methods can be of contact and noncontact subtypes. Laser micro-etching is a precise noncontact ablative denture marking technique that could be used for prostheses-guided personal identification.

[Chronic inflammation and organismal aging].

PubMed

Naito, Atsuhiko T; Komuro, Issei

2013-01-01

Aging is defined as the progressive functional decline of tissue function accompanied by increasing mortality with advancing age. Many researchers proposed various theories of aging, however, precise molecular mechanism of organismal aging remains elusive. The presence of autoantibody and the concentration of various inflammatory cytokines are often correlated to age, even in healthy individuals who do not have autoimmune or infectious diseases. In addition, low grade chronic inflammation has been regarded as a background for many age-related human diseases. These findings suggest that chronic inflammation plays a causative role in organismal aging and that proper regulation of aged immune system may decelerate organismal aging.

Molecular Mechanisms of SH2- and PTB-Domain-Containing Proteins in Receptor Tyrosine Kinase Signaling

PubMed Central

Wagner, Melany J.; Stacey, Melissa M.; Liu, Bernard A.; Pawson, Tony

2013-01-01

Intracellular signaling is mediated by reversible posttranslational modifications (PTMs) that include phosphorylation, ubiquitination, and acetylation, among others. In response to extracellular stimuli such as growth factors, receptor tyrosine kinases (RTKs) typically dimerize and initiate signaling through phosphorylation of their cytoplasmic tails and downstream scaffolds. Signaling effectors are recruited to these phosphotyrosine (pTyr) sites primarily through Src homology 2 (SH2) domains and pTyr-binding (PTB) domains. This review describes how these conserved domains specifically recognize pTyr residues and play a major role in mediating precise downstream signaling events. PMID:24296166

Molecular mechanisms of SH2- and PTB-domain-containing proteins in receptor tyrosine kinase signaling.

PubMed

Wagner, Melany J; Stacey, Melissa M; Liu, Bernard A; Pawson, Tony

2013-12-01

Intracellular signaling is mediated by reversible posttranslational modifications (PTMs) that include phosphorylation, ubiquitination, and acetylation, among others. In response to extracellular stimuli such as growth factors, receptor tyrosine kinases (RTKs) typically dimerize and initiate signaling through phosphorylation of their cytoplasmic tails and downstream scaffolds. Signaling effectors are recruited to these phosphotyrosine (pTyr) sites primarily through Src homology 2 (SH2) domains and pTyr-binding (PTB) domains. This review describes how these conserved domains specifically recognize pTyr residues and play a major role in mediating precise downstream signaling events.

Ciclopirox 1% shampoo for the treatment of seborrheic dermatitis.

PubMed

Gupta, Aditya K; Nicol, Karyn A

2006-01-01

Seborrheic dermatitis is a chronic superficial fungal infection of the skin, particularly affecting sites rich in sebaceous glands. Although the precise etiology of seborrheic dermatitis is uncertain, yeasts of the genus Malassezia are known to play a causative role. Ciclopirox is a broad-spectrum, hydroxypyridone-derived, synthetic antifungal agent, which also has anti-inflammatory properties. Ciclopirox is effective both in vitro and in vivo against Malassezia yeasts, making it a valuable option for the treatment of seborrheic dermatitis. Varying frequencies and concentrations of ciclopirox shampoo have been shown to be effective and safe in the treatment of seborrheic dermatitis of the scalp.

Role of the epidermal growth factor receptor in signaling strain-dependent activation of the brain natriuretic peptide gene.

PubMed

Anderson, Hope D I; Wang, Feng; Gardner, David G

2004-03-05

The epidermal growth factor receptor (EGFR) and ectoshedding of heparin-binding epidermal growth factor (HBEGF), an EGFR ligand, have been linked to the development of cardiac myocyte hypertrophy. However, the precise role that the liganded EGFR plays in the transcriptional activation of the gene program that accompanies hypertrophy remains undefined. Utilizing the human (h) BNP gene as a model of hypertrophy-dependent gene activation, we show that activation of the EGFR plays an important role in mediating mechanical strain-dependent stimulation of the hBNP promoter. Strain promotes endothelin (ET) generation through NAD(P)H oxidase-dependent production of reactive oxygen species. ET in turn induces metalloproteinase-mediated cleavage of pro-HBEGF and ectoshedding of HBEGF, which activates the EGFR and stimulates hBNP promoter activity. HBEGF also stimulates other phenotypic markers of hypertrophy including protein synthesis and sarcomeric assembly. The antioxidant N-acetylcysteine or the NAD(P)H oxidase inhibitor, apocynin, inhibited strain-dependent activation of the ET-1 promoter, HBEGF shedding, and hBNP promoter activation. The metalloproteinase inhibitor, GM-6001, prevented the induction of HBEGF ectoshedding and the hBNP promoter response to strain, suggesting a critical role for the metalloproteinase-dependent cleavage event in signaling the strain response. These findings suggest that metalloproteinase activity as an essential step in this pathway may prove to be a relevant therapeutic target in the management of cardiac hypertrophy.

Role of Autophagy in Metabolic Syndrome-Associated Heart Disease

PubMed Central

Ren, Sidney Y.; Xu, Xihui

2014-01-01

Metabolic syndrome (MetS) is a constellation of multiple metabolic risk factors including abdominal obesity, glucose intolerance, insulin resistance, dyslipidemia and hypertension. Over the past decades, the prevalence of metabolic syndrome has increased dramatically, imposing a devastating, pandemic health threat. More importantly, individuals with metabolic syndrome are at an increased risk of diabetes mellitus and overall cardiovascular diseases. One of the common comorbidities of metabolic syndrome is heart anomalies leading to the loss of cardiomyocytes, cardiac dysfunction and ultimately heart failure. Up-to-date, a plethora cell signaling pathways have been postulated for the pathogenesis of cardiac complications in obesity including lipotoxicity, inflammation, oxidative stress, apoptosis and sympathetic overactivation although the precise mechanism of action underscoring obesity-associated heart dysfunction remains elusive. Recent evidence has indicated a potential role of protein quality control in components of metabolic syndrome. Within the protein quality control system, the autophagy-lysosome pathway is an evolutionarily conserved pathway responsible for bulk degradation of large intracellular organelles and protein aggregates. Autophagy has been demonstrated to play an indispensible role in the maintenance of cardiac geometry and function under both physiological and pathological conditions. Accumulating studies have demonstrated that autophagy plays a pivotal role in the etiology of cardiac anomalies under obesity and metabolic syndrome. In this mini review, we will discuss on how autophagy is involved in the regulation of cardiac function in obesity and metabolic syndrome. PMID:24810277

Disruption of centrifugal inhibition to olfactory bulb granule cells impairs olfactory discrimination.

PubMed

Nunez-Parra, Alexia; Maurer, Robert K; Krahe, Krista; Smith, Richard S; Araneda, Ricardo C

2013-09-03

Granule cells (GCs) are the most abundant inhibitory neuronal type in the olfactory bulb and play a critical role in olfactory processing. GCs regulate the activity of principal neurons, the mitral cells, through dendrodendritic synapses, shaping the olfactory bulb output to other brain regions. GC excitability is regulated precisely by intrinsic and extrinsic inputs, and this regulation is fundamental for odor discrimination. Here, we used channelrhodopsin to stimulate GABAergic axons from the basal forebrain selectively and show that this stimulation generates reliable inhibitory responses in GCs. Furthermore, selective in vivo inhibition of GABAergic neurons in the basal forebrain by targeted expression of designer receptors exclusively activated by designer drugs produced a reversible impairment in the discrimination of structurally similar odors, indicating an important role of these inhibitory afferents in olfactory processing.

The Roles and Regulation of Polycomb Complexes in Neural Development

PubMed Central

Corley, Matthew; Kroll, Kristen L.

2014-01-01

In the developing mammalian nervous system, common progenitors integrate both cell extrinsic and intrinsic regulatory programs to produce distinct neuronal and glial cell types as development proceeds. This spatiotemporal restriction of neural progenitor differentiation is enforced, in part, by the dynamic reorganization of chromatin into repressive domains by Polycomb Repressive Complexes, effectively limiting the expression of fate-determining genes. Here, we review distinct roles that the Polycomb Repressive Complexes play during neurogenesis and gliogenesis, while also highlighting recent work describing the molecular mechanisms that govern their dynamic activity in neural development. Further investigation of how Polycomb complexes are regulated in neural development will enable more precise manipulation of neural progenitor differentiation, facilitating the efficient generation of specific neuronal and glial cell types for many biological applications. PMID:25367430

Dragging ras back in the ring.

PubMed

Stephen, Andrew G; Esposito, Dominic; Bagni, Rachel K; McCormick, Frank

2014-03-17

Ras proteins play a major role in human cancers but have not yielded to therapeutic attack. Ras-driven cancers are among the most difficult to treat and often excluded from therapies. The Ras proteins have been termed "undruggable," based on failures from an era in which understanding of signaling transduction, feedback loops, redundancy, tumor heterogeneity, and Ras' oncogenic role was poor. Structures of Ras oncoproteins bound to their effectors or regulators are unsolved, and it is unknown precisely how Ras proteins activate their downstream targets. These knowledge gaps have impaired development of therapeutic strategies. A better understanding of Ras biology and biochemistry, coupled with new ways of targeting undruggable proteins, is likely to lead to new ways of defeating Ras-driven cancers. Copyright © 2014 Elsevier Inc. All rights reserved.

The biology and function of exosomes in cancer

PubMed Central

Kalluri, Raghu

2016-01-01

Humans circulate quadrillions of exosomes at all times. Exosomes are a class of extracellular vesicles released by all cells, with a size range of 40–150 nm and a lipid bilayer membrane. Exosomes contain DNA, RNA, and proteins. Exosomes likely remove excess and/or unnecessary constituents from the cells, functioning like garbage bags, although their precise physiological role remains unknown. Additionally, exosomes may mediate specific cell-to-cell communication and activate signaling pathways in cells they fuse or interact with. Exosomes are detected in the tumor microenvironment, and emerging evidence suggests that they play a role in facilitating tumorigenesis by regulating angiogenesis, immunity, and metastasis. Circulating exosomes can be used as liquid biopsies and noninvasive biomarkers for early detection, diagnosis, and treatment of cancer patients. PMID:27035812

Science 101: How Do Atomic Clocks Work?

ERIC Educational Resources Information Center

Science and Children, 2008

2008-01-01

You might be wondering why in the world we need such precise measures of time. Well, many systems we use everyday, such as Global Positioning Systems, require precise synchronization of time. This comes into play in telecommunications and wireless communications, also. For purely scientific reasons, we can use precise measurement of time to…

Emerging roles of Hippo signaling in inflammation and YAP-driven tumor immunity.

PubMed

Zhou, Yuhang; Huang, Tingting; Zhang, Jinglin; Cheng, Alfred S L; Yu, Jun; Kang, Wei; To, Ka Fai

2018-07-10

Initially identified as a cell and organ size controller, Hippo pathway turns into a hotspot for researchers. Within recent years, more and more mechanisms about Hippo pathway were uncovered. Even though Hippo signaling has been revealed to exert controversial roles according to different cell context and microenvironment, which is because of its diversified interplays with a great variety of signaling transduction cascades; mechanisms other than size-limitation, however, remain to be elucidated. Recently, a growing number of studies tend to put Hippo on inflammatory and immunological focus: its antimicrobial role in flies, its pro- or anti-inflammation in mammals, as well as its relevance to cancerous immunity. From inflammation to tumor immunogenicity, Hippo has been gradually justified to play a crucial role. This review summarized the latest findings regarding the involvement of Hippo pathway in immunity, and a more comprehensive understanding of Hippo pathway will shed light on clinical translational potential even precision medicine. Copyright © 2018 Elsevier B.V. All rights reserved.

Emerging Roles for the Lysosome in Lipid Metabolism.

PubMed

Thelen, Ashley M; Zoncu, Roberto

2017-11-01

Precise regulation of lipid biosynthesis, transport, and storage is key to the homeostasis of cells and organisms. Cells rely on a sophisticated but poorly understood network of vesicular and nonvesicular transport mechanisms to ensure efficient delivery of lipids to target organelles. The lysosome stands at the crossroads of this network due to its ability to process and sort exogenous and endogenous lipids. The lipid-sorting function of the lysosome is intimately connected to its recently discovered role as a metabolic command-and-control center, which relays multiple nutrient cues to the master growth regulator, mechanistic target of rapamycin complex (mTORC)1 kinase. In turn, mTORC1 potently drives anabolic processes, including de novo lipid synthesis, while inhibiting lipid catabolism. Here, we describe the dual role of the lysosome in lipid transport and biogenesis, and we discuss how integration of these two processes may play important roles both in normal physiology and in disease. Copyright © 2017 Elsevier Ltd. All rights reserved.

Role of the recombinant protein of the platelet receptor for type I collagen in the release of nitric oxide during platelet aggregation.

PubMed

Chiang, T M; Wang, Y B; Kang, E S

2000-12-01

Nitric oxide plays an important role in platelet function and platelets possess the endothelial isoform of nitric oxide synthase. Several reports have indicated that nitric oxide is released upon exposure of platelets to collagen. We have reported that a non-integrin platelet protein of 65 kDa is a receptor for type I collagen. By direct measurement of NO release from washed human platelets suspended in Tyrode buffer with a ISO-NO Mark II, World Precision Instruments, Sarasota, FL, USA, p30 sensor, type I collagen, but not ADP and epinephrine, induces the release of NO in a time-dependent manner. The production of NO is inhibited either by preincubation of type I collagen with the platelet type I collagen receptor recombinant protein or by preincubation of platelets with the antibody to the receptor protein, the anti-65 antibody. However, preincubation of platelets with anti-P-selectin and anti-glycoprotein IIb/IIIa did not affect the release of NO by platelets. These results suggest that the 65 kDa platelet receptor for type I collagen is specifically linked to the generation of NO, and that the 65 kDa platelet receptor for type I collagen plays an important new role in platelet function.

The influence of submarine groundwater discharge on greenhouse gas evasion from coastal waters (Invited)

NASA Astrophysics Data System (ADS)

Santos, I. R.

2013-12-01

Coastal waters are thought to play a major role on global carbon budgets but we still lack a quantitative understanding about some mechanisms driving greenhouse gas cycling in coastal waters. Very little is known about the role of submarine groundwater discharge (SGD) in delivering carbon to rivers, estuaries and coastal waters even though the concentrations of most carbon species in groundwater are often much higher than those in surface waters. I hypothesize that SGD plays a significant role in coastal carbon and greenhouse gas budgets even if the volumetric SGD contribution is small. I will report new, detailed observations of radon (a natural groundwater tracer) and carbon dioxide and methane concentrations and stable isotopes in tidal rivers, estuaries, coastal wetlands, mangroves and coral reef lagoons. Groundwater exchange at these contrasting sites was driven by a wide range of processes, including terrestrial hydraulic gradients, tidal pumping, and convection. In all systems, SGD was an important source of carbon dioxide, DIC, and methane to surface waters. In some cases, groundwater seepage alone could account for 100% of carbon dioxide evasion from surface waters to the atmosphere. Combining high precision in situ radon and greenhouse gas concentration and stable isotope observations allows for an effective, unambiguous assessment of how groundwater seepage drives carbon dynamics in surface waters.

Contingency Management with Human Autonomy Teaming

NASA Technical Reports Server (NTRS)

Shively, Robert J.; Lachter, Joel B.

2018-01-01

Automation is playing an increasingly important role in many operations. It is often cheaper faster and more precise than human operators. However, automation is not perfect. There are many situations in which a human operator must step in. We refer to these instances as contingencies and the act of stepping in contingency management. Here we propose coupling Human Autonomy Teaming (HAT) with contingency management. We describe two aspects to HAT, bi-directional communication, and working agreements (or plays). Bi-directional communication like Crew Resource Management in traditional aviation, allows all parties to contribute to a decision. Working agreements specify roles and responsibilities. Importantly working agreements allow for the possibility of roles and responsibilities changing depending on environmental factors (e.g., situations the automation was not designed for, workload, risk, or trust). This allows for the automation to "automatically" become more autonomous as it becomes more trusted and/or it is updated to deal with a more complete set of possible situations. We present a concrete example using a prototype contingency management station one might find in a future airline operations center. Automation proposes reroutes for aircraft that encounter bad weather or are forced to divert for environmental or systems reasons. If specific conditions are met, these recommendations may be autonomously datalinked to the affected aircraft.

Promotion of plant growth by Pseudomonas fluorescens strain SS101 via novel volatile organic compounds.

PubMed

Park, Yong-Soon; Dutta, Swarnalee; Ann, Mina; Raaijmakers, Jos M; Park, Kyungseok

2015-05-29

Volatile organic compounds (VOCs) from plant growth-promoting rhizobacteria (PGPR) play key roles in modulating plant growth and induced systemic resistance (ISR) to pathogens. Despite their significance, the physiological functions of the specific VOCs produced by Pseudomonas fluorescens SS101 (Pf.SS101) have not been precisely elucidated. The effects of Pf.SS101 and its VOCs on augmentation of plant growth promotion were investigated in vitro and in planta. A significant growth promotion was observed in plants exposed Pf.SS101 under both conditions, suggesting that its VOCs play a key role in promoting plant growth. Solid-phase micro-extraction (SPME) and a gas chromatography-mass spectrophotometer (GC-MS) system were used to characterize the VOCs emitted by Pf.SS101 and 11 different compounds were detected in samples inoculated this bacterium, including 13-Tetradecadien-1-ol, 2-butanone and 2-Methyl-n-1-tridecene. Application of these compounds resulted in enhanced plant growth. This study suggests that Pf.SS101 promotes the growth of plants via the release of VOCs including 13-Tetradecadien-1-ol, 2-butanone and 2-Methyl-n-1-tridecene, thus increasing understanding of the role of VOCs in plant-bacterial inter-communication. Copyright © 2015 Elsevier Inc. All rights reserved.

The NADPH Oxidases DUOX1 and NOX2 Play Distinct Roles in Redox Regulation of Epidermal Growth Factor Receptor Signaling.

PubMed

Heppner, David E; Hristova, Milena; Dustin, Christopher M; Danyal, Karamatullah; Habibovic, Aida; van der Vliet, Albert

2016-10-28

The epidermal growth factor receptor (EGFR) plays a critical role in regulating airway epithelial homeostasis and responses to injury. Activation of EGFR is regulated by redox-dependent processes involving reversible cysteine oxidation by reactive oxygen species (ROS) and involves both ligand-dependent and -independent mechanisms, but the precise source(s) of ROS and the molecular mechanisms that control tyrosine kinase activity are incompletely understood. Here, we demonstrate that stimulation of EGFR activation by ATP in airway epithelial cells is closely associated with dynamic reversible oxidation of cysteine residues via sequential sulfenylation and S-glutathionylation within EGFR and the non-receptor-tyrosine kinase Src. Moreover, the intrinsic kinase activity of recombinant Src or EGFR was in both cases enhanced by H 2 O 2 but not by GSSG, indicating that the intermediate sulfenylation is the activating modification. H 2 O 2 -induced increase in EGFR tyrosine kinase activity was not observed with the C797S variant, confirming Cys-797 as the redox-sensitive cysteine residue that regulates kinase activity. Redox-dependent regulation of EGFR activation in airway epithelial cells was found to strongly depend on activation of either the NADPH oxidase DUOX1 or the homolog NOX2, depending on the activation mechanism. Whereas DUOX1 and Src play a primary role in EGFR transactivation by wound-derived signals such as ATP, direct ligand-dependent EGFR activation primarily involves NOX2 with a secondary role for DUOX1 and Src. Collectively, our findings establish that redox-dependent EGFR kinase activation involves a dynamic and reversible cysteine oxidation mechanism and that this activation mechanism variably involves DUOX1 and NOX2. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Differential regulation of the transcriptional activity of the glucocorticoid receptor through site-specific phosphorylation.

PubMed

Kumar, Raj; Calhoun, William J

2008-12-01

Post-translational modifications such as phosphorylation are known to play an important role in the gene regulation by the transcription factors including the nuclear hormone receptor superfamily of which the glucocorticoid receptor (GR) is a member. Protein phosphorylation often switches cellular activity from one state to another. Like many other transcription factors, the GR is a phosphoprotein, and phosphorylation plays an important role in the regulation of GR activity. Cell signaling pathways that regulate phosphorylation of the GR and its associated proteins are important determinants of GR function under various physiological conditions. While the role of many phosphorylation sites in the GR is still not fully understood, the role of others is clearer. Several aspects of transcription factor function, including DNA binding affinity, interaction of transactivation domains with the transcription initiation complex, and shuttling between the cytoplasmic compartments, have all been linked to site-specific phosphorylation. All major phosphorylation sites in the human GR are located in the N-terminal domain including the major transactivation domain, AF1. Available literature clearly indicates that many of these potential phosphorylation sites are substrates for multiple kinases, suggesting the potential for a very complex regulatory network. Phosphorylated GR interacts favorably with critical coregulatory proteins and subsequently enhances transcriptional activity. In addition, the activities and specificities of coregulators may be subject to similar regulation by phosphorylation. Regulation of the GR activity due to phosphorylation appears to be site-specific and dependent upon specific cell signaling cascade. Taken together, site-specific phosphorylation and related kinase pathways play an important role in the action of the GR, and more precise mechanistic information will lead to fuller understanding of the complex nature of gene regulation by the GR- and related transcription factors. This review provides currently available information regarding the role of GR phosphorylation in its action, and highlights the possible underlying mechanisms of action.

Design and analysis of a 3D Elliptical Micro-Displacement Motion Stage

NASA Astrophysics Data System (ADS)

Lin, Jieqiong; Zhao, Dongpo; Lu, Mingming; Zhou, Jiakang

2017-12-01

Micro-displacement motion stage driven by piezoelectric actuator has a significant demand in the field of ultra-precision machining in recent years, while the design of micro-displacement motion stage plays an important role to realize a large displacement output and high precision control. Thus, a 3D elliptical micro-displacement motion stage driven by three PZT actuators has been developed. Firstly, the 3D elliptical trajectory of this motion stage could be adjusted through the form of the PZT actuators input signal. Then, the desired trajectory was obtained by adjusting the micro displacement of the motion stage in 3D elliptical space. Finally, the trajectory simulation and the finite element simulation were applied in this motion stage. The experimental results shown that, the output displacement of the three directions under the input force of the 1600N were 14μm, 16μm and 74μm, respectively. And the first three modes were 1471.6Hz, 2698.4Hz and 2803.4Hz, respectively. Analysis and experiments were carried out to verify the performance, result proved that a large output displacement and high precision control could be obtained.

THE MIRA–TITAN UNIVERSE: PRECISION PREDICTIONS FOR DARK ENERGY SURVEYS

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

Heitmann, Katrin; Habib, Salman; Biswas, Rahul

2016-04-01

Large-scale simulations of cosmic structure formation play an important role in interpreting cosmological observations at high precision. The simulations must cover a parameter range beyond the standard six cosmological parameters and need to be run at high mass and force resolution. A key simulation-based task is the generation of accurate theoretical predictions for observables using a finite number of simulation runs, via the method of emulation. Using a new sampling technique, we explore an eight-dimensional parameter space including massive neutrinos and a variable equation of state of dark energy. We construct trial emulators using two surrogate models (the linear powermore » spectrum and an approximate halo mass function). The new sampling method allows us to build precision emulators from just 26 cosmological models and to systematically increase the emulator accuracy by adding new sets of simulations in a prescribed way. Emulator fidelity can now be continuously improved as new observational data sets become available and higher accuracy is required. Finally, using one ΛCDM cosmology as an example, we study the demands imposed on a simulation campaign to achieve the required statistics and accuracy when building emulators for investigations of dark energy.« less

The mira-titan universe. Precision predictions for dark energy surveys

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

Heitmann, Katrin; Bingham, Derek; Lawrence, Earl

2016-03-28

Large-scale simulations of cosmic structure formation play an important role in interpreting cosmological observations at high precision. The simulations must cover a parameter range beyond the standard six cosmological parameters and need to be run at high mass and force resolution. A key simulation-based task is the generation of accurate theoretical predictions for observables using a finite number of simulation runs, via the method of emulation. Using a new sampling technique, we explore an eight-dimensional parameter space including massive neutrinos and a variable equation of state of dark energy. We construct trial emulators using two surrogate models (the linear powermore » spectrum and an approximate halo mass function). The new sampling method allows us to build precision emulators from just 26 cosmological models and to systematically increase the emulator accuracy by adding new sets of simulations in a prescribed way. Emulator fidelity can now be continuously improved as new observational data sets become available and higher accuracy is required. Finally, using one ΛCDM cosmology as an example, we study the demands imposed on a simulation campaign to achieve the required statistics and accuracy when building emulators for investigations of dark energy.« less

Station-Keeping Requirements for Astronomical Imaging with Constellations of Free-Flying Collectors

NASA Technical Reports Server (NTRS)

Allen, Ronald J.

2004-01-01

The requirements on station-keeping for constellations of free-flying collectors coupled as (future) imaging arrays in space for astrophysics applications are discussed. The typical knowledge precision required in the plane of the array depends on the angular size of the targets of interest; it is generally at a level of tens of centimeters for typical stellar targets, becoming of order centimeters only for the widest attainable fields of view. In the "piston" direction, perpendicular to the array, the typical knowledge precision required depends on the bandwidth of the signal, and is at a level of tens of wavelengths for narrow approx. 1% signal bands, becoming of order one wavelength only for the broadest bandwidths expected to be useful. The significance of this result is that, at this level of precision, it may be possible to provide the necessary knowledge of array geometry without the use of signal photons, thereby allowing observations of faint targets. "Closure-phase" imaging is a technique which has been very successfully applied to surmount instabilities owing to equipment and to the atmosphere, and which appears to be directly applicable to space imaging arrays where station-keeping drifts play the same role as (slow) atmospheric and equipment instabilities.

Performance Evaluation of Frequency Transform Based Block Classification of Compound Image Segmentation Techniques

NASA Astrophysics Data System (ADS)

Selwyn, Ebenezer Juliet; Florinabel, D. Jemi

2018-04-01

Compound image segmentation plays a vital role in the compression of computer screen images. Computer screen images are images which are mixed with textual, graphical, or pictorial contents. In this paper, we present a comparison of two transform based block classification of compound images based on metrics like speed of classification, precision and recall rate. Block based classification approaches normally divide the compound images into fixed size blocks of non-overlapping in nature. Then frequency transform like Discrete Cosine Transform (DCT) and Discrete Wavelet Transform (DWT) are applied over each block. Mean and standard deviation are computed for each 8 × 8 block and are used as features set to classify the compound images into text/graphics and picture/background block. The classification accuracy of block classification based segmentation techniques are measured by evaluation metrics like precision and recall rate. Compound images of smooth background and complex background images containing text of varying size, colour and orientation are considered for testing. Experimental evidence shows that the DWT based segmentation provides significant improvement in recall rate and precision rate approximately 2.3% than DCT based segmentation with an increase in block classification time for both smooth and complex background images.

Convergent microRNA actions coordinate neocortical development.

PubMed

Barca-Mayo, Olga; De Pietri Tonelli, Davide

2014-08-01

Neocortical development is a complex process that, at the cellular level, involves tight control of self-renewal, cell fate commitment, survival, differentiation and delamination/migration. These processes require, at the molecular level, the precise regulation of intrinsic signaling pathways and extrinsic factors with coordinated action in a spatially and temporally specific manner. Transcriptional regulation plays an important role during corticogenesis; however, microRNAs (miRNAs) are emerging as important post-transcriptional regulators of various aspects of central nervous system development. miRNAs are a class of small, single-stranded noncoding RNA molecules that control the expression of the majority of protein coding genes (i.e., targets). How do different miRNAs achieve precise control of gene networks during neocortical development? Here, we critically review all the miRNA-target interactions validated in vivo, with relevance to the generation and migration of pyramidal-projection glutamatergic neurons, and for the initial formation of cortical layers in the embryonic development of rodent neocortex. In particular, we focus on convergent miRNA actions, which are still a poorly understood layer of complexity in miRNA signaling, but potentially one of the keys to disclosing how miRNAs achieve the precise coordination of complex biological processes such as neocortical development.

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

Laskin, Julia; Johnson, Grant E.; Prabhakaran, Venkateshkumar

Immobilization of complex molecules and clusters on supports plays an important role in a variety of disciplines including materials science, catalysis and biochemistry. In particular, deposition of clusters on surfaces has attracted considerable attention due to their non-scalable, highly size-dependent properties. The ability to precisely control the composition and morphology of clusters and small nanoparticles on surfaces is crucial for the development of next generation materials with rationally tailored properties. Soft- and reactive landing of ions onto solid or liquid surfaces introduces unprecedented selectivity into surface modification by completely eliminating the effect of solvent and sample contamination on the qualitymore » of the film. The ability to select the mass-to-charge ratio of the precursor ion, its kinetic energy and charge state along with precise control of the size, shape and position of the ion beam on the deposition target makes soft-landing an attractive approach for surface modification. High-purity uniform thin films on surfaces generated using mass-selected ion deposition facilitate understanding of critical interfacial phenomena relevant to catalysis, energy generation and storage, and materials science. Our efforts have been directed toward understanding charge retention by soft-landed metal and metal-oxide cluster ions, which may affect both their structure and reactivity. Specifically, we have examined the effect of the surface on charge retention by both positively and negatively charged cluster ions. We found that the electronic properties of the surface play an important role in charge retention by cluster cations. Meanwhile, the electron binding energy is a key factor determining charge retention by cluster anions. These findings provide the scientific foundation for the rational design of interfaces for advanced catalysts and energy storage devices. Further optimization of electrode-electrolyte interfaces for applications in energy storage and electrocatalysis may be achieved by understanding and controlling the properties of soft-landed cluster ions.« less

StemTextSearch: Stem cell gene database with evidence from abstracts.

PubMed

Chen, Chou-Cheng; Ho, Chung-Liang

2017-05-01

Previous studies have used many methods to find biomarkers in stem cells, including text mining, experimental data and image storage. However, no text-mining methods have yet been developed which can identify whether a gene plays a positive or negative role in stem cells. StemTextSearch identifies the role of a gene in stem cells by using a text-mining method to find combinations of gene regulation, stem-cell regulation and cell processes in the same sentences of biomedical abstracts. The dataset includes 5797 genes, with 1534 genes having positive roles in stem cells, 1335 genes having negative roles, 1654 genes with both positive and negative roles, and 1274 with an uncertain role. The precision of gene role in StemTextSearch is 0.66, and the recall is 0.78. StemTextSearch is a web-based engine with queries that specify (i) gene, (ii) category of stem cell, (iii) gene role, (iv) gene regulation, (v) cell process, (vi) stem-cell regulation, and (vii) species. StemTextSearch is available through http://bio.yungyun.com.tw/StemTextSearch.aspx. Copyright © 2017. Published by Elsevier Inc.

Rituals of creativity: tradition, modernity, and the "acoustic unconscious" in a U.S. collegiate jazz music program.

PubMed

Wilf, Eitan

2012-01-01

In this article, I seek to complicate the distinction between imitation and creativity, which has played a dominant role in the modern imaginary and anthropological theory. I focus on a U.S. collegiate jazz music program, in which jazz educators use advanced sound technologies to reestablish immersive interaction with the sounds of past jazz masters against the backdrop of the disappearance of performance venues for jazz. I analyze a key pedagogical practice in the course of which students produce precise replications of the recorded improvisations of past jazz masters and then play them in synchrony with the recordings. Through such synchronous iconization, students inhabit and reenact the creativity epitomized by these recordings. I argue that such a practice, which I call a “ritual of creativity,” suggests a coconstitutive relationship between imitation and creativity, which has intensified under modernity because of the availability of new technologies of digital reproduction.

Analysis of calibration accuracy of cameras with different target sizes for large field of view

NASA Astrophysics Data System (ADS)

Zhang, Jin; Chai, Zhiwen; Long, Changyu; Deng, Huaxia; Ma, Mengchao; Zhong, Xiang; Yu, Huan

2018-03-01

Visual measurement plays an increasingly important role in the field o f aerospace, ship and machinery manufacturing. Camera calibration of large field-of-view is a critical part of visual measurement . For the issue a large scale target is difficult to be produced, and the precision can not to be guaranteed. While a small target has the advantage of produced of high precision, but only local optimal solutions can be obtained . Therefore, studying the most suitable ratio of the target size to the camera field of view to ensure the calibration precision requirement of the wide field-of-view is required. In this paper, the cameras are calibrated by a series of different dimensions of checkerboard calibration target s and round calibration targets, respectively. The ratios of the target size to the camera field-of-view are 9%, 18%, 27%, 36%, 45%, 54%, 63%, 72%, 81% and 90%. The target is placed in different positions in the camera field to obtain the camera parameters of different positions . Then, the distribution curves of the reprojection mean error of the feature points' restructure in different ratios are analyzed. The experimental data demonstrate that with the ratio of the target size to the camera field-of-view increas ing, the precision of calibration is accordingly improved, and the reprojection mean error changes slightly when the ratio is above 45%.

A system view and analysis of essential hypertension.

PubMed

Botzer, Alon; Grossman, Ehud; Moult, John; Unger, Ron

2018-05-01

The goal of this study was to investigate genes associated with essential hypertension from a system perspective, making use of bioinformatic tools to gain insights that are not evident when focusing at a detail-based resolution. Using various databases (pathways, Genome Wide Association Studies, knockouts etc.), we compiled a set of about 200 genes that play a major role in hypertension and identified the interactions between them. This enabled us to create a protein-protein interaction network graph, from which we identified key elements, based on graph centrality analysis. Enriched gene regulatory elements (transcription factors and microRNAs) were extracted by motif finding techniques and knowledge-based tools. We found that the network is composed of modules associated with functions such as water retention, endothelial vasoconstriction, sympathetic activity and others. We identified the transcription factor SP1 and the two microRNAs miR27 (a and b) and miR548c-3p that seem to play a major role in regulating the network as they exert their control over several modules and are not restricted to specific functions. We also noticed that genes involved in metabolic diseases (e.g. insulin) are central to the network. We view the blood-pressure regulation mechanism as a system-of-systems, composed of several contributing subsystems and pathways rather than a single module. The system is regulated by distributed elements. Understanding this mode of action can lead to a more precise treatment and drug target discovery. Our analysis suggests that insulin plays a primary role in hypertension, highlighting the tight link between essential hypertension and diseases associated with the metabolic syndrome.

The relationship between soil management and the Sustainable Development Goals: the case of global banana production

NASA Astrophysics Data System (ADS)

Stoorvogel, Jetse; Segura, Rafael; Erima, Rockefeller

2017-04-01

The Sustainable Development Goals (SDGs) are a good example of the increasing demand on our soil resources. Our soil resources play a central role in multiple SDGs while talking about poverty (SDG 1), food security (SDG 2), clean energy through biofuels (SDG 7), climate mitigation (SDG 13), and land degradation (SDG 15). This means that basic decisions on soil management are now placed in the context of multiple soil functions. A good example is the global production of bananas and plantains with a total harvested area of almost 10 million ha. While the export bananas played a central role in economic development, an even larger share of the production plays a role in food security. Nevertheless, the production is also criticized due the intensive use of agricultural chemicals (fertilizers and pesticides) and the risk of soil degradation in the monoculture plantations. Decisions on soil management are context specific and depending on the environment. In this study we will analyse and discuss three production environments from the Philippines, Uganda, and Costa Rica. The role of the SDGs in the regions is very different. Where SDG 1 and SDG15 play an important role in the Costa Rican situation, SDG 2 is more important in Uganda and the Philippines. Decisions on soil management strongly depend on the agro-ecology with the available technological packages. The technological packages include low external input farming, organic farming, precision agriculture, and so-called best management practices. While producers take decisions at the field and farm level, we are now increasingly forced for joined action at the regional level with the rapid spread of highly virulent crop diseases. The SDGs have major consequences for soil management but this study shows that, at the same time, they cannot be translated one-to-one to the farm level at which the management decisions are taken. Therefore, off-farm effects and externalities are often not considered in farm management except if they are explicitly being targeted by policies or other interventions. Specific attention is required to analyse the aggregated effect of soil management decisions at the regional level.

Why Physics in Medicine?

PubMed

Samei, Ehsan; Grist, Thomas M

2018-05-18

Despite its crucial role in the development of new medical imaging technologies, in clinical practice, physics has primarily been involved in the technical evaluation of technologies. However, this narrow role is no longer adequate. New trajectories in medicine call for a stronger role for physics in the clinic. The movement toward evidence-based, quantitative, and value-based medicine requires physicists to play a more integral role in delivering innovative precision care through the intentional clinical application of physical sciences. There are three aspects of this clinical role: technology assessment based on metrics as they relate to expected clinical performance, optimized use of technologies for patient-centered clinical outcomes, and retrospective analysis of imaging operations to ensure attainment of expectations in terms of quality and variability. These tasks fuel the drive toward high-quality, consistent practice of medical imaging that is patient centered, evidence based, and safe. While this particular article focuses on imaging, this trajectory and paradigm is equally applicable to the multitudes of the applications of physics in medicine. Copyright © 2018 American College of Radiology. Published by Elsevier Inc. All rights reserved.

From technological advances to biological understanding: The main steps toward high-precision RT in breast cancer.

PubMed

Leonardi, Maria Cristina; Ricotti, Rosalinda; Dicuonzo, Samantha; Cattani, Federica; Morra, Anna; Dell'Acqua, Veronica; Orecchia, Roberto; Jereczek-Fossa, Barbara Alicja

2016-10-01

Radiotherapy improves local control in breast cancer (BC) patients which increases overall survival in the long term. Improvements in treatment planning and delivery and a greater understanding of BC behaviour have laid the groundwork for high-precision radiotherapy, which is bound to further improve the therapeutic index. Precise identification of target volumes, better coverage and dose homogeneity have had a positive impact on toxicity and local control. The conformity of treatment dose due to three-dimensional radiotherapy and new techniques such as intensity modulated radiotherapy makes it possible to spare surrounding normal tissue. The widespread use of dose-volume constraints and histograms have increased awareness of toxicity. Real time image guidance has improved geometric precision and accuracy, together with the implementation of quality assurance programs. Advances in the precision of radiotherapy is also based on the choice of the appropriate fractionation and approach. Adaptive radiotherapy is not only a technical concept, but is also a biological concept based on the knowledge that different types of BC have distinctive patterns of locoregional spread. A greater understanding of cancer biology helps in choosing the treatment best suited to a particular situation. Biomarkers predictive of response play a crucial role. The combination of radiotherapy with molecular targeted therapies may enhance radiosensitivity, thus increasing the cytotoxic effects and improving treatment response. The appropriateness of an alternative fractionation, partial breast irradiation, dose escalating/de-escalating approaches, the extent of nodal irradiation have been examined for all the BC subtypes. The broadened concept of adaptive radiotherapy is vital to high-precision treatments. Copyright © 2016 Elsevier Ltd. All rights reserved.

The role of dopamine in human addiction: from reward to motivated attention.

PubMed

Franken, Ingmar H A; Booij, Jan; van den Brink, Wim

2005-12-05

There is general consensus among preclinical researchers that dopamine plays an important role in the development and persistence of addiction. However, the precise role of dopamine in addictive behaviors is far from clear and only a few clinical studies on the role of dopamine in human addiction have been conducted so far. The present paper reviews studies addressing the role of dopamine in humans. There is substantial and consistent evidence that dopamine is involved in the experience of drug reward in humans. Dopamine may also be involved in motivational processes such as drug craving. However, given the inconsistent findings of studies using dopamine receptor (ant)agonists, the role of dopamine in the experience of craving is far from resolved. Recent theories claiming that dopamine signals salience and makes the brain paying attention to biological relevant stimuli may provide an interesting framework for explaining addictive behaviors. There is accumulating evidence that patients with drug and alcohol addiction have an aberrant focus on drug-related stimuli. Although there is some preliminary support for the role of dopamine in these attention processes, more studies have to be carried out in order to test the validity of these theories in human subjects.

Direct 3-D morphological measurements of silicone rubber impression using micro-focus X-ray CT.

PubMed

Kamegawa, Masayuki; Nakamura, Masayuki; Fukui, Yu; Tsutsumi, Sadami; Hojo, Masaki

2010-01-01

Three-dimensional computer models of dental arches play a significant role in prosthetic dentistry. The microfocus X-ray CT scanner has the advantage of capturing precise 3D shapes of deep fossa, and we propose a new method of measuring the three-dimensional morphology of a dental impression directly, which will eliminate the conversion process to dental casts. Measurement precision and accuracy were evaluated using a standard gage comprised of steel balls which simulate the dental arch. Measurement accuracy, standard deviation of distance distribution of superimposed models, was determined as +/-0.050 mm in comparison with a CAD model. Impressions and casts of an actual dental arch were scanned by microfocus X-ray CT and three-dimensional models were compared. The impression model had finer morphology, especially around the cervical margins of teeth. Within the limitations of the current study, direct three-dimensional impression modeling was successfully demonstrated using microfocus X-ray CT.

Information encoded in non-native states drives substrate-chaperone pairing.

PubMed

Mapa, Koyeli; Tiwari, Satyam; Kumar, Vignesh; Jayaraj, Gopal Gunanathan; Maiti, Souvik

2012-09-05

Many proteins refold in vitro through kinetic folding intermediates that are believed to be by-products of native-state centric evolution. These intermediates are postulated to play only minor roles, if any, in vivo because they lack any information related to translation-associated vectorial folding. We demonstrate that refolding intermediate of a test protein, generated in vitro, is able to find its cognate chaperone, from the whole complement of Escherichia coli soluble chaperones. Cognate chaperone-binding uniquely alters the conformation of non-native substrate. Importantly, precise chaperone targeting of substrates are maintained as long as physiological molar ratios of chaperones remain unaltered. Using a library of different chaperone substrates, we demonstrate that kinetically trapped refolding intermediates contain sufficient structural features for precise targeting to cognate chaperones. We posit that evolution favors sequences that, in addition to coding for a functional native state, encode folding intermediates with higher affinity for cognate chaperones than noncognate ones. Copyright © 2012 Elsevier Ltd. All rights reserved.

Clinical utility of BOLD fMRI in preoperative work-up of epilepsy

PubMed Central

Ganesan, Karthik; Ursekar, Meher

2014-01-01

Surgical techniques have emerged as a viable therapeutic option in patients with drug refractory epilepsy. Pre-surgical evaluation of epilepsy requires a comprehensive, multiparametric, and multimodal approach for precise localization of the epileptogenic focus. Various non-invasive techniques are available at the disposal of the treating physician to detect the epileptogenic focus, which include electroencephalography (EEG), video-EEG, magnetic resonance imaging (MRI), functional MRI including blood oxygen level dependent (BOLD) techniques, single photon emission tomography (SPECT), and 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET). Currently, non-invasive high-resolution MR imaging techniques play pivotal roles in the preoperative detection of the seizure focus, and represent the foundation for successful epilepsy surgery. BOLD functional magnetic resonance imaging (fMRI) maps allow for precise localization of the eloquent cortex in relation to the seizure focus. This review article focuses on the clinical utility of BOLD (fMRI) in the pre-surgical work-up of epilepsy patients. PMID:24851002

Emerging lattice approach to the K-unitarity triangle

DOE PAGES

Lehner, Christoph; Lunghi, Enrico; Soni, Amarjit

2016-05-04

In this study, it has been clear for the past several years that new physics in the quark sector can only appear, in low energy observables, as a perturbation. Therefore precise theoretical predictions and precise experimental measurements have become mandatory. Here we draw attention to the significant advances that have been made in lattice QCD simulations in recent years in K→ππ, in the long-distance contribution to indirect CP violation in the Kaon system (ε) and in rare K-decays. Thus, in conjunction with experiments, the construction of a unitarity triangle purely from Kaon physics should soon become feasible. We want tomore » emphasize that in our approach to the K -unitarity triangle, the ability of lattice QCD methods to systematically improve the calculation of the direct CP-violation parameter (ε') plays a pivotal role. Along with the B-unitarity triangle, this could allow, depending on the pattern of new physics, for more stringent tests of the Standard Model and tighter constraints on new physics.« less

Advanced CD-SEM solution for edge placement error characterization of BEOL pitch 32nm metal layers

NASA Astrophysics Data System (ADS)

Charley, A.; Leray, P.; Lorusso, G.; Sutani, T.; Takemasa, Y.

2018-03-01

Metrology plays an important role in edge placement error (EPE) budgeting. Control for multi-patterning applications as new critical distances needs to be measured (edge to edge) and requirements become tighter and tighter in terms of accuracy and precision. In this paper we focus on imec iN7 BEOL platform and particularly on M2 patterning scheme using SAQP + block EUV for a 7.5 track logic design. Being able to characterize block to SAQP edge misplacement is important in a budgeting exercise (1) but is also extremely difficult due to challenging edge detection with CD-SEM (similar materials, thin layers, short distances, 3D features). In this study we develop an advanced solution to measure block to SAQP placement, we characterize it in terms of sensitivity, precision and accuracy through the comparison to reference metrology. In a second phase, the methodology is applied to budget local effects and the results are compared to the characterization of the SAQP and block independently.

Assessment of Gamma-Ray-Spectra Analysis Method Utilizing the Fireworks Algorithm for Various Error Measures

DOE PAGES

Alamaniotis, Miltiadis; Tsoukalas, Lefteri H.

2018-01-01

The analysis of measured data plays a significant role in enhancing nuclear nonproliferation mainly by inferring the presence of patterns associated with special nuclear materials. Among various types of measurements, gamma-ray spectra is the widest utilized type of data in nonproliferation applications. In this paper, a method that employs the fireworks algorithm (FWA) for analyzing gamma-ray spectra aiming at detecting gamma signatures is presented. In particular, FWA is utilized to fit a set of known signatures to a measured spectrum by optimizing an objective function, where non-zero coefficients express the detected signatures. FWA is tested on a set of experimentallymore » obtained measurements optimizing various objective functions—MSE, RMSE, Theil-2, MAE, MAPE, MAP—with results exhibiting its potential in providing highly accurate and precise signature detection. Finally and furthermore, FWA is benchmarked against genetic algorithms and multiple linear regression, showing its superiority over those algorithms regarding precision with respect to MAE, MAPE, and MAP measures.« less

MEMS-based beam-steerable free-space optical communication link for reconfigurable wireless data center

NASA Astrophysics Data System (ADS)

Deng, Peng; Kavehrad, Mohsen; Lou, Yan

2017-01-01

Flexible wireless datacenter networks based on free space optical communication (FSO) links are being considered as promising solutions to meet the future datacenter demands of high throughput, robustness to dynamic traffic patterns, cabling complexity and energy efficiency. Robust and precise steerable FSO links over dynamic traffic play a key role in the reconfigurable optical wireless datacenter inter-rack network. In this work, we propose and demonstrate a reconfigurable 10Gbps FSO system incorporated with smart beam acquisition and tracking mechanism based on gimballess two-axis MEMS micro-mirror and retro-reflective film marked aperture. The fast MEMS-based beam acquisition switches laser beam of FSO terminal from one rack to the next for reconfigurable networks, and the precise beam tracking makes FSO device auto-correct the misalignment in real-time. We evaluate the optical power loss and bit error rate performance of steerable FSO links at various directions. Experimental results suggest that the MEMS based beam steerable FSO links hold considerable promise for the future reconfigurable wireless datacenter networks.

Parameters Identification for Photovoltaic Module Based on an Improved Artificial Fish Swarm Algorithm

PubMed Central

Wang, Hong-Hua

2014-01-01

A precise mathematical model plays a pivotal role in the simulation, evaluation, and optimization of photovoltaic (PV) power systems. Different from the traditional linear model, the model of PV module has the features of nonlinearity and multiparameters. Since conventional methods are incapable of identifying the parameters of PV module, an excellent optimization algorithm is required. Artificial fish swarm algorithm (AFSA), originally inspired by the simulation of collective behavior of real fish swarms, is proposed to fast and accurately extract the parameters of PV module. In addition to the regular operation, a mutation operator (MO) is designed to enhance the searching performance of the algorithm. The feasibility of the proposed method is demonstrated by various parameters of PV module under different environmental conditions, and the testing results are compared with other studied methods in terms of final solutions and computational time. The simulation results show that the proposed method is capable of obtaining higher parameters identification precision. PMID:25243233

Selective-area growth and controlled substrate coupling of transition metal dichalcogenides

NASA Astrophysics Data System (ADS)

Bersch, Brian M.; Eichfeld, Sarah M.; Lin, Yu-Chuan; Zhang, Kehao; Bhimanapati, Ganesh R.; Piasecki, Aleksander F.; Labella, Michael, III; Robinson, Joshua A.

2017-06-01

Developing a means for true bottom-up, selective-area growth of two-dimensional (2D) materials on device-ready substrates will enable synthesis in regions only where they are needed. Here, we demonstrate seed-free, site-specific nucleation of transition metal dichalcogenides (TMDs) with precise control over lateral growth by utilizing an ultra-thin polymeric surface functionalization capable of precluding nucleation and growth. This polymer functional layer (PFL) is derived from conventional photoresists and lithographic processing, and is compatible with multiple growth techniques, precursors (metal organics, solid-source) and TMDs. Additionally, we demonstrate that the substrate can play a major role in TMD transport properties. With proper TMD/substrate decoupling, top-gated field-effect transistors (FETs) fabricated with selectively-grown monolayer MoS2 channels are competitive with current reported MoS2 FETs. The work presented here demonstrates that substrate surface engineering is key to realizing precisely located and geometrically-defined 2D layers via unseeded chemical vapor deposition techniques.

Role of Monomer Sequence, Hydrogen Bonding and Mesoscale Architecture in Marine Antifouling Coatings

NASA Astrophysics Data System (ADS)

Segalman, Rachel

Polypeptoids are non-natural, sequence specific polymers that offer the opportunity to probe the effect of monomer sequence, chirality, and chain shape on self-assembly and surface properties. Additionally, polypeptoid synthesis is more scaleable than traditional polypeptides suggesting their utility in large area applications. We have designed efficient marine anti-fouling coatings by using triblock copolymer scaffolds to which polypeptoids are tethered in order to tune both the modulus and surface energies with great precision. Surprisingly, when short sequences are tethered to a polymer backbone, polypeptoids consistently outperform analogous polypeptides in antifouling properties. We hypothesize that the hydrogen bonding inherent to the polypeptide backbone drives the observed differences in performance. We also find that the polymer scaffold housing the polypeptoids also plays a crucial role in directing surface presentation and therefore the overall coating properties.

The role of space telescopes in the characterization of transiting exoplanets.

PubMed

Hatzes, Artie P

2014-09-18

Characterization studies now have a dominant role in the field of exoplanets. Such studies include the measurement of an exoplanet's bulk density, its brightness temperature and the chemical composition of its atmosphere. The use of space telescopes has played a key part in the characterization of transiting exoplanets. These facilities offer astronomers data of exquisite precision and temporal sampling as well as access to wavelength regions of the electromagnetic spectrum that are inaccessible from the ground. Space missions such as the Hubble Space Telescope, Microvariability and Oscillations of Stars (MOST), Spitzer Space Telescope, Convection, Rotation and Planetary Transits (CoRoT), and Kepler have rapidly advanced our knowledge of the physical properties of exoplanets and have blazed a trail for a series of future space missions that will help us to understand the observed diversity of exoplanets.

Centrioles: some self-assembly required.

PubMed

Song, Mi Hye; Miliaras, Nicholas B; Peel, Nina; O'Connell, Kevin F

2008-12-01

Centrioles play an important role in organizing microtubules and are precisely duplicated once per cell cycle. New (daughter) centrioles typically arise in association with existing (mother) centrioles (canonical assembly), suggesting that mother centrioles direct the formation of daughter centrioles. However, under certain circumstances, centrioles can also selfassemble free of an existing centriole (de novo assembly). Recent work indicates that the canonical and de novo pathways utilize a common mechanism and that a mother centriole spatially constrains the self-assembly process to occur within its immediate vicinity. Other recently identified mechanisms further regulate canonical assembly so that during each cell cycle, one and only one daughter centriole is assembled per mother centriole.

Are There Levels of Consciousness?

PubMed

Bayne, Tim; Hohwy, Jakob; Owen, Adrian M

2016-06-01

The notion of a level of consciousness is a key construct in the science of consciousness. Not only is the term employed to describe the global states of consciousness that are associated with post-comatose disorders, epileptic absence seizures, anaesthesia, and sleep, it plays an increasingly influential role in theoretical and methodological contexts. However, it is far from clear what precisely a level of consciousness is supposed to be. This paper argues that the levels-based framework for conceptualizing global states of consciousness is untenable and develops in its place a multidimensional account of global states. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Performance of Geant4 in simulating semiconductor particle detector response in the energy range below 1 MeV

NASA Astrophysics Data System (ADS)

Soti, G.; Wauters, F.; Breitenfeldt, M.; Finlay, P.; Kraev, I. S.; Knecht, A.; Porobić, T.; Zákoucký, D.; Severijns, N.

2013-11-01

Geant4 simulations play a crucial role in the analysis and interpretation of experiments providing low energy precision tests of the Standard Model. This paper focuses on the accuracy of the description of the electron processes in the energy range between 100 and 1000 keV. The effect of the different simulation parameters and multiple scattering models on the backscattering coefficients is investigated. Simulations of the response of HPGe and passivated implanted planar Si detectors to β particles are compared to experimental results. An overall good agreement is found between Geant4 simulations and experimental data.

Reinforcement learning in complementarity game and population dynamics

NASA Astrophysics Data System (ADS)

Jost, Jürgen; Li, Wei

2014-02-01

We systematically test and compare different reinforcement learning schemes in a complementarity game [J. Jost and W. Li, Physica A 345, 245 (2005), 10.1016/j.physa.2004.07.005] played between members of two populations. More precisely, we study the Roth-Erev, Bush-Mosteller, and SoftMax reinforcement learning schemes. A modified version of Roth-Erev with a power exponent of 1.5, as opposed to 1 in the standard version, performs best. We also compare these reinforcement learning strategies with evolutionary schemes. This gives insight into aspects like the issue of quick adaptation as opposed to systematic exploration or the role of learning rates.

Flexible processing and the design of grammar.

PubMed

Sag, Ivan A; Wasow, Thomas

2015-02-01

We explore the consequences of letting the incremental and integrative nature of language processing inform the design of competence grammar. What emerges is a view of grammar as a system of local monotonic constraints that provide a direct characterization of the signs (the form-meaning correspondences) of a given language. This "sign-based" conception of grammar has provided precise solutions to the key problems long thought to motivate movement-based analyses, has supported three decades of computational research developing large-scale grammar implementations, and is now beginning to play a role in computational psycholinguistics research that explores the use of underspecification in the incremental computation of partial meanings.

Platelet function is modified by common sequence variation in megakaryocyte super enhancers

PubMed Central

Petersen, Romina; Lambourne, John J.; Javierre, Biola M.; Grassi, Luigi; Kreuzhuber, Roman; Ruklisa, Dace; Rosa, Isabel M.; Tomé, Ana R.; Elding, Heather; van Geffen, Johanna P.; Jiang, Tao; Farrow, Samantha; Cairns, Jonathan; Al-Subaie, Abeer M.; Ashford, Sofie; Attwood, Antony; Batista, Joana; Bouman, Heleen; Burden, Frances; Choudry, Fizzah A.; Clarke, Laura; Flicek, Paul; Garner, Stephen F.; Haimel, Matthias; Kempster, Carly; Ladopoulos, Vasileios; Lenaerts, An-Sofie; Materek, Paulina M.; McKinney, Harriet; Meacham, Stuart; Mead, Daniel; Nagy, Magdolna; Penkett, Christopher J.; Rendon, Augusto; Seyres, Denis; Sun, Benjamin; Tuna, Salih; van der Weide, Marie-Elise; Wingett, Steven W.; Martens, Joost H.; Stegle, Oliver; Richardson, Sylvia; Vallier, Ludovic; Roberts, David J.; Freson, Kathleen; Wernisch, Lorenz; Stunnenberg, Hendrik G.; Danesh, John; Fraser, Peter; Soranzo, Nicole; Butterworth, Adam S.; Heemskerk, Johan W.; Turro, Ernest; Spivakov, Mikhail; Ouwehand, Willem H.; Astle, William J.; Downes, Kate; Kostadima, Myrto; Frontini, Mattia

2017-01-01

Linking non-coding genetic variants associated with the risk of diseases or disease-relevant traits to target genes is a crucial step to realize GWAS potential in the introduction of precision medicine. Here we set out to determine the mechanisms underpinning variant association with platelet quantitative traits using cell type-matched epigenomic data and promoter long-range interactions. We identify potential regulatory functions for 423 of 565 (75%) non-coding variants associated with platelet traits and we demonstrate, through ex vivo and proof of principle genome editing validation, that variants in super enhancers play an important role in controlling archetypical platelet functions. PMID:28703137

Dreaming and Neuroesthetics

PubMed Central

Barcaro, Umberto; Paoli, Marco

2015-01-01

This paper, which is limited to the art of painting, aims to support the idea that a substantial insertion of concepts and methods drawn on dream psychology and dream neuroscience can contribute to the advancements of Neuroesthetics. The historical and scientific reasons are discussed that have determined the so far poor role played by the dream phenomenon in the developments of Neuroesthetics. In the light of recent advancements in psychophysiological research, a method of analyzing artistic products is proposed that is based on the recognition of precise features proper of the dreaming experience. Four examples are given for application of this method, regarding works by Giorgione, Leonardo da Vinci, Vermeer, and Millais, respectively. PMID:26157373

Application of optical coherence tomography attenuation imaging for quantification of optical properties in medulloblastoma

NASA Astrophysics Data System (ADS)

Vuong, Barry; Skowron, Patryk; Kiehl, Tim-Rasmus; Kyan, Matthew; Garzia, Livia; Genis, Helen; Sun, Cuiru; Taylor, Michael D.; Yang, Victor X. D.

2015-03-01

The hemodynamic environment is known to play a crucial role in the progression, rupture, and treatment of intracranial aneurysms. Currently there is difficulty assessing and measuring blood flow profiles in vivo. An emerging high resolution imaging modality known as split spectrum Doppler optical coherence tomography (ssDOCT) has demonstrated the capability to quantify hemodynamic patterns as well as arterial microstructural changes. In this study, we present a novel in vitro method to acquire precise blood flow patterns within a patient- specific aneurysm silicone flow models using ssDOCT imaging. Computational fluid dynamics (CFD) models were generated to verify ssDOCT results.

[Testicular cancer: a model to optimize the radiological follow-up].

PubMed

Stebler, V; Pauchard, B; Schmidt, S; Valerio, M; De Bari, B; Berthold, D

2015-05-20

Despite being rare cancers, testicular seminoma and non-seminoma play an important role in oncology: they represent a model on how to optimize radiological follow-up, aiming at a lowest possible radiation exposure and secondary cancer risk. Males diagnosed with testicular cancer undergo frequently prolonged follow-up with CT-scans with potential toxic side effects, in particular secondary cancers. To reduce the risks linked to ionizing radiation, precise follow-up protocols have been developed. The number of recommended CT-scanners has been significantly reduced over the last 10 years. The CT scanners have evolved technically and new acquisition protocols have the potential to reduce the radiation exposure further.

Molecular Imaging and Precision Medicine in Head and Neck Cancer.

PubMed

Mena, Esther; Thippsandra, Shwetha; Yanamadala, Anusha; Redy, Siddaling; Pattanayak, Puskar; Subramaniam, Rathan M

2017-01-01

The concept of using tumor genomic profiling information has revolutionized personalized cancer treatment. Head and neck (HN) cancer management is being influenced by recent discoveries of activating mutations in epidermal growth factor receptor and related targeted therapies with tyrosine kinase inhibitors, targeted therapies for Kristen Rat Sarcoma, and MET proto-oncogenes. Molecular imaging using PET plays an important role in assessing the biologic behavior of HN cancer with the goal of delivering individualized cancer treatment. This review summarizes recent genomic discoveries in HN cancer and their implications for functional PET imaging in assessing response to targeted therapies, and drug resistance mechanisms. Copyright © 2016 Elsevier Inc. All rights reserved.

Belle II silicon vertex detector

NASA Astrophysics Data System (ADS)

Adamczyk, K.; Aihara, H.; Angelini, C.; Aziz, T.; Babu, V.; Bacher, S.; Bahinipati, S.; Barberio, E.; Baroncelli, Ti.; Baroncelli, To.; Basith, A. K.; Batignani, G.; Bauer, A.; Behera, P. K.; Bergauer, T.; Bettarini, S.; Bhuyan, B.; Bilka, T.; Bosi, F.; Bosisio, L.; Bozek, A.; Buchsteiner, F.; Casarosa, G.; Ceccanti, M.; Červenkov, D.; Chendvankar, S. R.; Dash, N.; Divekar, S. T.; Doležal, Z.; Dutta, D.; Enami, K.; Forti, F.; Friedl, M.; Hara, K.; Higuchi, T.; Horiguchi, T.; Irmler, C.; Ishikawa, A.; Jeon, H. B.; Joo, C. W.; Kandra, J.; Kang, K. H.; Kato, E.; Kawasaki, T.; Kodyš, P.; Kohriki, T.; Koike, S.; Kolwalkar, M. M.; Kvasnička, P.; Lanceri, L.; Lettenbicher, J.; Maki, M.; Mammini, P.; Mayekar, S. N.; Mohanty, G. B.; Mohanty, S.; Morii, T.; Nakamura, K. R.; Natkaniec, Z.; Negishi, K.; Nisar, N. K.; Onuki, Y.; Ostrowicz, W.; Paladino, A.; Paoloni, E.; Park, H.; Pilo, F.; Profeti, A.; Rashevskaya, I.; Rao, K. K.; Rizzo, G.; Rozanska, M.; Sandilya, S.; Sasaki, J.; Sato, N.; Schultschik, S.; Schwanda, C.; Seino, Y.; Shimizu, N.; Stypula, J.; Suzuki, J.; Tanaka, S.; Tanida, K.; Taylor, G. N.; Thalmeier, R.; Thomas, R.; Tsuboyama, T.; Uozumi, S.; Urquijo, P.; Vitale, L.; Volpi, M.; Watanuki, S.; Watson, I. J.; Webb, J.; Wiechczynski, J.; Williams, S.; Würkner, B.; Yamamoto, H.; Yin, H.; Yoshinobu, T.; Belle II SVD Collaboration

2016-09-01

The Belle II experiment at the SuperKEKB collider in Japan is designed to indirectly probe new physics using approximately 50 times the data recorded by its predecessor. An accurate determination of the decay-point position of subatomic particles such as beauty and charm hadrons as well as a precise measurement of low-momentum charged particles will play a key role in this pursuit. These will be accomplished by an inner tracking device comprising two layers of pixelated silicon detector and four layers of silicon vertex detector based on double-sided microstrip sensors. We describe herein the design, prototyping and construction efforts of the Belle-II silicon vertex detector.

Fine-grained state counting for black holes in loop quantum gravity.

PubMed

Ghosh, A; Mitra, P

2009-04-10

A state of a black hole in loop quantum gravity is given by a distribution of spins on punctures on the horizon. The distribution is of the Boltzmann type, with the area playing the role of the energy. In investigations where the total area was kept approximately constant, there was a kind of thermal equilibrium between the spins which have the same analogue temperature and the entropy was proportional to the area. If the area is precisely fixed, however, multiple constraints appear, different spins have different analogue temperatures and the entropy is not strictly linear in the area, but is bounded by a linear rise.

Sensitivity, Specificity, PPV, and NPV for Predictive Biomarkers.

PubMed

Simon, Richard

2015-08-01

Molecularly targeted cancer drugs are often developed with companion diagnostics that attempt to identify which patients will have better outcome on the new drug than the control regimen. Such predictive biomarkers are playing an increasingly important role in precision oncology. For diagnostic tests, sensitivity, specificity, positive predictive value, and negative predictive are usually used as performance measures. This paper discusses these indices for predictive biomarkers, provides methods for their calculation with survival or response endpoints, and describes assumptions involved in their use. Published by Oxford University Press 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Wire in the Cable-Driven System of Surgical Robot

NASA Astrophysics Data System (ADS)

Wang, X. F.; Lv, N.; Mu, H. Z.; Xue, L. J.

2017-07-01

During the evolution of the surgical robot, cable plays an important role. It translates motion and force precisely from surgeon’s hand to the tool’s tips. In the paper, the vertical wires, the composition of cable, are mathematically modeled from a geometric point of view. The cable structure and tension are analyzed according to the characteristics of wire screw twist. The structural equations of the wires in different positions are derived for both non-bent cable and bent cable, respectively. The bending moment formula of bent cable is also obtained. This will help researchers find suitable cable and design more matched pulley.

Butyric acid in irritable bowel syndrome.

PubMed

Załęski, Andrzej; Banaszkiewicz, Aleksandra; Walkowiak, Jarosław

2013-01-01

Butyric acid (butanoic acid) belongs to a group of short-chain fatty acids and is thought to play several beneficial roles in the gastrointestinal tract. Butyric anion is easily absorbed by enteric cells and used as a main source of energy. Moreover, butyric acid is an important regulator of colonocyte proliferation and apoptosis, gastrointestinal tract motility and bacterial microflora composition in addition to its involvement in many other processes including immunoregulation and anti-inflammatory activity. The pathogenesis of irritable bowel syndrome (IBS), the most commonly diagnosed functional gastrointestinal condition, is complex, and its precise mechanisms are still unclear. This article describes the potential benefits of butyric acid in IBS.

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

Benedict, Stanley H.; Bova, Frank J.; Clark, Brenda

This article is a tribute to the pioneering medical physicists over the last 50 years who have participated in the research, development, and commercialization of stereotactic radiosurgery (SRS) and stereotactic radiotherapy utilizing a wide range of technology. The authors have described the evolution of SRS through the eyes of physicists from its beginnings with the Gamma Knife in 1951 to proton and charged particle therapy; modification of commercial linacs to accommodate high precision SRS setups; the multitude of accessories that have enabled fine tuning patients for relocalization, immobilization, and repositioning with submillimeter accuracy; and finally the emerging technology of SBRT.more » A major theme of the article is the expanding role of the medical physicist from that of advisor to the neurosurgeon to the current role as a primary driver of new technology that has already led to an adaptation of cranial SRS to other sites in the body, including, spine, liver, and lung. SRS continues to be at the forefront of the impetus to provide technological precision for radiation therapy and has demonstrated a host of downstream benefits in improving delivery strategies for conventional therapy as well. While this is not intended to be a comprehensive history, and the authors could not delineate every contribution by all of those working in the pursuit of SRS development, including physicians, engineers, radiobiologists, and the rest of the therapy and dosimetry staff in this important and dynamic radiation therapy modality, it is clear that physicists have had a substantial role in the development of SRS and theyincreasingly play a leading role in furthering SRS technology.« less

Host-Microbiome Interaction and Cancer: Potential Application in Precision Medicine

PubMed Central

Contreras, Alejandra V.; Cocom-Chan, Benjamin; Hernandez-Montes, Georgina; Portillo-Bobadilla, Tobias; Resendis-Antonio, Osbaldo

2016-01-01

It has been experimentally shown that host-microbial interaction plays a major role in shaping the wellness or disease of the human body. Microorganisms coexisting in human tissues provide a variety of benefits that contribute to proper functional activity in the host through the modulation of fundamental processes such as signal transduction, immunity and metabolism. The unbalance of this microbial profile, or dysbiosis, has been correlated with the genesis and evolution of complex diseases such as cancer. Although this latter disease has been thoroughly studied using different high-throughput (HT) technologies, its heterogeneous nature makes its understanding and proper treatment in patients a remaining challenge in clinical settings. Notably, given the outstanding role of host-microbiome interactions, the ecological interactions with microorganisms have become a new significant aspect in the systems that can contribute to the diagnosis and potential treatment of solid cancers. As a part of expanding precision medicine in the area of cancer research, efforts aimed at effective treatments for various kinds of cancer based on the knowledge of genetics, biology of the disease and host-microbiome interactions might improve the prediction of disease risk and implement potential microbiota-directed therapeutics. In this review, we present the state of the art of sequencing and metabolome technologies, computational methods and schemes in systems biology that have addressed recent breakthroughs of uncovering relationships or associations between microorganisms and cancer. Together, microbiome studies extend the horizon of new personalized treatments against cancer from the perspective of precision medicine through a synergistic strategy integrating clinical knowledge, HT data, bioinformatics, and systems biology. PMID:28018236

Expression, localization and possible functions of aquaporins 3 and 8 in rat digestive system.

PubMed

Zhao, G X; Dong, P P; Peng, R; Li, J; Zhang, D Y; Wang, J Y; Shen, X Z; Dong, L; Sun, J Y

2016-01-01

Although aquaporins (AQPs) play important roles in transcellular water movement, their precise quantification and localization remains controversial. We investigated expression levels and localizations of AQP3 and AQP8 and their possible functions in the rat digestive system using real-time polymerase chain reactions, western blot analysis and immunohistochemistry. We investigated the expression levels and localizations of AQP3 and AQP8 in esophagus, forestomach, glandular stomach, duodenum, jejunum, ileum, proximal and distal colon, and liver. AQP3 was expressed in the basolateral membranes of stratified epithelia (esophagus and forestomach) and simple columnar epithelia (glandular stomach, ileum, and proximal and distal colon). Expression was particularly abundant in the esophagus, and proximal and distal colon. AQP8 was found in the subapical compartment of columnar epithelial cells of the jejunum, ileum, proximal colon and liver; the most intense staining occurred in the jejunum. Our results suggest that AQP3 and AQP8 play significant roles in intestinal function and/or fluid homeostasis and may be an important subject for future investigation of disorders that involve disruption of intestinal fluid homeostasis, such as inflammatory bowel disease and irritable bowel syndrome.

Dopamine Precursor Depletion Influences Pain Affect Rather than Pain Sensation

PubMed Central

Schulz, Enrico; Baumkötter, Jochen; Ploner, Markus

2014-01-01

Pain is a multidimensional experience, which includes sensory, cognitive, and affective aspects. Converging lines of evidence indicate that dopaminergic neurotransmission plays an important role in human pain perception. However, the precise effects of dopamine on different aspects of pain perception remain to be elucidated. To address this question, we experimentally decreased dopaminergic neurotransmission in 22 healthy human subjects using Acute Phenylalanine and Tyrosine Depletion (APTD). During APTD and a control condition we applied brief painful laser stimuli to the hand, assessed different aspects of pain perception, and recorded electroencephalographic responses. APTD-induced decreases of cerebral dopaminergic activity did not influence sensory aspects of pain perception. In contrast, APTD yielded increases of pain unpleasantness. The increases of unpleasantness ratings positively correlated with effectiveness of APTD. Our finding of an influence of dopaminergic neurotransmission on affective but not sensory aspects of phasic pain suggests that analgesic effects of dopamine might be mediated by indirect effects on pain affect rather than by direct effects on ascending nociceptive signals. These findings contribute to our understanding of the complex relationship between dopamine and pain perception, which may play a role in various clinical pain states. PMID:24760082

Bariatric Surgery and Precision Nutrition

PubMed Central

Nicoletti, Carolina F.; Cortes-Oliveira, Cristiana; Pinhel, Marcela A. S.; Nonino, Carla B.

2017-01-01

This review provides a literature overview of new findings relating nutritional genomics and bariatric surgery. It also describes the importance of nutritional genomics concepts in personalized bariatric management. It includes a discussion of the potential role bariatric surgery plays in altering the three pillars of nutritional genomics: nutrigenetics, nutrigenomics, and epigenetics. We present studies that show the effect of each patient’s genetic and epigenetic variables on the response to surgical weight loss treatment. We include investigations that demonstrate the association of single nucleotide polymorphisms with obesity phenotypes and their influence on weight loss after bariatric surgery. We also present reports on how significant weight loss induced by bariatric surgery impacts telomere length, and we discuss studies on the existence of an epigenetic signature associated with surgery outcomes and specific gene methylation profile, which may help to predict weight loss after a surgical procedure. Finally, we show articles which evidence that bariatric surgery may affect expression of numerous genes involved in different metabolic pathways and consequently induce functional and taxonomic changes in gut microbial communities. The role nutritional genomics plays in responses to weight loss after bariatric surgery is evident. Better understanding of the molecular pathways involved in this process is necessary for successful weight management and maintenance. PMID:28878180

Bariatric Surgery and Precision Nutrition.

PubMed

Nicoletti, Carolina F; Cortes-Oliveira, Cristiana; Pinhel, Marcela A S; Nonino, Carla B

2017-09-06

This review provides a literature overview of new findings relating nutritional genomics and bariatric surgery. It also describes the importance of nutritional genomics concepts in personalized bariatric management. It includes a discussion of the potential role bariatric surgery plays in altering the three pillars of nutritional genomics: nutrigenetics, nutrigenomics, and epigenetics. We present studies that show the effect of each patient's genetic and epigenetic variables on the response to surgical weight loss treatment. We include investigations that demonstrate the association of single nucleotide polymorphisms with obesity phenotypes and their influence on weight loss after bariatric surgery. We also present reports on how significant weight loss induced by bariatric surgery impacts telomere length, and we discuss studies on the existence of an epigenetic signature associated with surgery outcomes and specific gene methylation profile, which may help to predict weight loss after a surgical procedure. Finally, we show articles which evidence that bariatric surgery may affect expression of numerous genes involved in different metabolic pathways and consequently induce functional and taxonomic changes in gut microbial communities. The role nutritional genomics plays in responses to weight loss after bariatric surgery is evident. Better understanding of the molecular pathways involved in this process is necessary for successful weight management and maintenance.

The capsule plays an important role in Escherichia coli K1 interactions with Acanthamoeba.

PubMed

Jung, Suk-Yul; Matin, Abdul; Kim, Kwang Sik; Khan, Naveed Ahmed

2007-03-01

Escherichia coli K1 is shown to bind to, associate with, invade and survive inside Acanthamoeba, but the precise mechanisms associated with these events are unclear. We have previously shown that outer membrane protein A and lipopolysaccharide are critical bacterial determinants involved in E. coli K1 interactions with Acanthamoeba. Using an isogenic K1 capsule-deletion mutant (lacking the neuDB genes cluster that is necessary for the production of cytoplasmic precursors to the exopolysaccharide capsule), we observed that the capsule modulates and enhances E. coli K1 association and survival inside Acanthamoeba. The capsule-deletion mutant exhibited significantly reduced association compared with the wild type strain, E44. Similarly, the K1 capsule-deletion mutant exhibited limited ability for invasion/uptake by and survival inside Acanthamoeba. Next, we determined whether E. coli K1 survive inside Acanthamoeba during the encystment process and that viable bacteria can be isolated from the mature cysts. Using encystment assays, our findings revealed that E. coli K1, but not its capsule-deletion mutant, exhibit survival inside Acanthamoeba cysts. We believe this is the first demonstration that the K1 capsule plays an important role in E. coli K1 interactions with Acanthamoeba.

Effect of the SH3-SH2 domain linker sequence on the structure of Hck kinase.

PubMed

Meiselbach, Heike; Sticht, Heinrich

2011-08-01

The coordination of activity in biological systems requires the existence of different signal transduction pathways that interact with one another and must be precisely regulated. The Src-family tyrosine kinases, which are found in many signaling pathways, differ in their physiological function despite their high overall structural similarity. In this context, the differences in the SH3-SH2 domain linkers might play a role for differential regulation, but the structural consequences of linker sequence remain poorly understood. We have therefore performed comparative molecular dynamics simulations of wildtype Hck and of a mutant Hck in which the SH3-SH2 domain linker is replaced by the corresponding sequence from the homologous kinase Lck. These simulations reveal that linker replacement not only affects the orientation of the SH3 domain itself, but also leads to an alternative conformation of the activation segment in the Hck kinase domain. The sequence of the SH3-SH2 domain linker thus exerts a remote effect on the active site geometry and might therefore play a role in modulating the structure of the inactive kinase or in fine-tuning the activation process itself.

Exploring the Relationship of Task Performance and Physical and Cognitive Fatigue During a Daylong Light Precision Task.

PubMed

Yung, Marcus; Manji, Rahim; Wells, Richard P

2017-11-01

Our aim was to explore the relationship between fatigue and operation system performance during a simulated light precision task over an 8-hr period using a battery of physical (central and peripheral) and cognitive measures. Fatigue may play an important role in the relationship between poor ergonomics and deficits in quality and productivity. However, well-controlled laboratory studies in this area have several limitations, including the lack of work relevance of fatigue exposures and lack of both physical and cognitive measures. There remains a need to understand the relationship between physical and cognitive fatigue and task performance at exposure levels relevant to realistic production or light precision work. Errors and fatigue measures were tracked over the course of a micropipetting task. Fatigue responses from 10 measures and errors in pipetting technique, precision, and targeting were submitted to principal component analysis to descriptively analyze features and patterns. Fatigue responses and error rates contributed to three principal components (PCs), accounting for 50.9% of total variance. Fatigue responses grouped within the three PCs reflected central and peripheral upper extremity fatigue, postural sway, and changes in oculomotor behavior. In an 8-hr light precision task, error rates shared similar patterns to both physical and cognitive fatigue responses, and/or increases in arousal level. The findings provide insight toward the relationship between fatigue and operation system performance (e.g., errors). This study contributes to a body of literature documenting task errors and fatigue, reflecting physical (both central and peripheral) and cognitive processes.

Induced pluripotent stem cell technology: Toward the future of cardiac arrhythmias.

PubMed

Gnecchi, Massimiliano; Stefanello, Manuela; Mura, Manuela

2017-06-15

The development of human induced pluripotent stem cell (iPSC) technology has revitalized the efforts made in the last decade to exploit the potential of human embryonic stem cells (ESCs) for scientific research. In the field of cardiac arrhythmias, the possibility of generating an unlimited amount of patient-specific cardiomyocyte-like cells (iPSC-CMs) has clear advantages compared with the use of ESC-derived cardiac cells. In particular, with the introduction and implementation of the large-scale precision medicine initiative, we anticipate that the iPSC technology will play an important role in the advancement of cardiovascular research and medicine. This platform is not free from technical limitations that must be carefully taken into account; however, the utility of iPSC-CMs in disease modeling and drug testing studies is hardly questionable. Here, we summarize some of the progresses made in the field of iPSC technology applied to inherited cardiac arrhythmias, with particular emphasis on the use of iPSC-CMs for modelling the long QT syndrome and for the development of personalized drug and molecular therapies. The growing role of iPSC technology in the practice of precision medicine will also be discussed. Copyright © 2017 Elsevier B.V. All rights reserved.

The role of spatial memory and frames of reference in the precision of angular path integration.

PubMed

Arthur, Joeanna C; Philbeck, John W; Kleene, Nicholas J; Chichka, David

2012-09-01

Angular path integration refers to the ability to maintain an estimate of self-location after a rotational displacement by integrating internally-generated (idiothetic) self-motion signals over time. Previous work has found that non-sensory inputs, namely spatial memory, can play a powerful role in angular path integration (Arthur et al., 2007, 2009). Here we investigated the conditions under which spatial memory facilitates angular path integration. We hypothesized that the benefit of spatial memory is particularly likely in spatial updating tasks in which one's self-location estimate is referenced to external space. To test this idea, we administered passive, non-visual body rotations (ranging 40°-140°) about the yaw axis and asked participants to use verbal reports or open-loop manual pointing to indicate the magnitude of the rotation. Prior to some trials, previews of the surrounding environment were given. We found that when participants adopted an egocentric frame of reference, the previously-observed benefit of previews on within-subject response precision was not manifested, regardless of whether remembered spatial frameworks were derived from vision or spatial language. We conclude that the powerful effect of spatial memory is dependent on one's frame of reference during self-motion updating. Copyright © 2012 Elsevier B.V. All rights reserved.

Structural basis for alpha fetoprotein-mediated inhibition of caspase-3 activity in hepatocellular carcinoma cells.

PubMed

Lin, Bo; Zhu, Mingyue; Wang, Wenting; Li, Wei; Dong, Xu; Chen, Yi; Lu, Yan; Guo, Junli; Li, Mengsen

2017-10-01

Alpha-fetoprotein (AFP) is an early serum growth factor in the foetal liver development and hepatic carcinogenesis; However, the precise biological role of cytoplasmic AFP remains elusive. Although we recently demonstrated that cytoplasmic AFP might interact with caspase-3 and inhibit the signal transduction of apoptosis in human hepatocellular carcinoma (HCC) cells, the details of this interaction are not clear. To reveal the molecular relationship between AFP and caspase-3, we performed molecular docking, co-immunoprecipitation (Co-IP), laser confocal microscopy, site-directed mutagenesis and functional experiments to analyse the key amino acid residues in the binding site of caspase-3. The results of Co-IP, laser confocal microscopy and functional analyses were consistent with the computational model. We also used the model to explain why AFP cannot bind to caspase-8. These results provide the molecular basis for the AFP-mediated inhibition of caspase-3 activity in HCC cells. Altogether, we found that AFP interacts with caspase-3 through precise amino acids, namely loop-4 residues Glu-248, Asp-253 and His-257. The results further demonstrated that AFP plays a critical role in the inhibition of the apoptotic signal transduction that mediated by caspase-3. Thus, AFP might represent a novel biotarget for the therapy of HCC patients. © 2017 UICC.

Seasonal Plasticity of Precise Spike Timing in the Avian Auditory System

PubMed Central

Sen, Kamal; Rubel, Edwin W; Brenowitz, Eliot A.

2015-01-01

Vertebrate audition is a dynamic process, capable of exhibiting both short- and long-term adaptations to varying listening conditions. Precise spike timing has long been known to play an important role in auditory encoding, but its role in sensory plasticity remains largely unexplored. We addressed this issue in Gambel's white-crowned sparrow (Zonotrichia leucophrys gambelii), a songbird that shows pronounced seasonal fluctuations in circulating levels of sex-steroid hormones, which are known to be potent neuromodulators of auditory function. We recorded extracellular single-unit activity in the auditory forebrain of males and females under different breeding conditions and used a computational approach to explore two potential strategies for the neural discrimination of sound level: one based on spike counts and one based on spike timing reliability. We report that breeding condition has robust sex-specific effects on spike timing. Specifically, in females, breeding condition increases the proportion of cells that rely solely on spike timing information and increases the temporal resolution required for optimal intensity encoding. Furthermore, in a functionally distinct subset of cells that are particularly well suited for amplitude encoding, female breeding condition enhances spike timing-based discrimination accuracy. No effects of breeding condition were observed in males. Our results suggest that high-resolution temporal discharge patterns may provide a plastic neural substrate for sensory coding. PMID:25716843

APETALA 2-domain-containing transcription factors: focusing on abscisic acid and gibberellins antagonism.

PubMed

Shu, Kai; Zhou, Wenguan; Yang, Wenyu

2018-02-01

The phytohormones abscisic acid (ABA) and gibberellin (GA) antagonistically mediate diverse plant developmental processes including seed dormancy and germination, root development, and flowering time control, and thus the optimal balance between ABA and GA is essential for plant growth and development. Although more than a half and one century have passed since the initial discoveries of ABA and GA, respectively, the precise mechanisms underlying ABA-GA antagonism still need further investigation. Emerging evidence indicates that two APETALA 2 (AP2)-domain-containing transcription factors (ATFs), ABI4 in Arabidopsis and OsAP2-39 in rice, play key roles in ABA and GA antagonism. These two transcription factors precisely regulate the transcription pattern of ABA and GA biosynthesis or inactivation genes, mediating ABA and GA levels. In this Viewpoint article, we try to shed light on the effects of ATFs on ABA-GA antagonism, and summarize the overlapping but distinct biological functions of these ATFs in the antagonism between ABA and GA. Finally, we strongly propose that further research is needed into the detailed roles of additional numerous ATFs in ABA and GA crosstalk, which will improve our understanding of the antagonism between these two phytohormones. © 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.

Sleep-Dependent Oscillatory Synchronization: A Role in Fear Memory Consolidation.

PubMed

Totty, Michael S; Chesney, Logan A; Geist, Phillip A; Datta, Subimal

2017-01-01

Sleep plays an important role in memory consolidation through the facilitation of neuronal plasticity; however, how sleep accomplishes this remains to be completely understood. It has previously been demonstrated that neural oscillations are an intrinsic mechanism by which the brain precisely controls neural ensembles. Inter-regional synchronization of these oscillations is also known to facilitate long-range communication and long-term potentiation (LTP). In the present study, we investigated how the characteristic rhythms found in local field potentials (LFPs) during non-REM and REM sleep play a role in emotional memory consolidation. Chronically implanted bipolar electrodes in the lateral amygdala (LA), dorsal and ventral hippocampus (DH, VH), and the infra-limbic (IL), and pre-limbic (PL) prefrontal cortex were used to record LFPs across sleep-wake activity following each day of a Pavlovian cued fear conditioning paradigm. This resulted in three principle findings: (1) theta rhythms during REM sleep are highly synchronized between regions; (2) the extent of inter-regional synchronization during REM and non-REM sleep is altered by FC and EX; (3) the mean phase difference of synchronization between the LA and VH during REM sleep predicts changes in freezing after cued fear extinction. These results both oppose a currently proposed model of sleep-dependent memory consolidation and provide a novel finding which suggests that the role of REM sleep theta rhythms in memory consolidation may rely more on the relative phase-shift between neural oscillations, rather than the extent of phase synchronization.

Impact of Labile Zinc on Heart Function: From Physiology to Pathophysiology.

PubMed

Turan, Belma; Tuncay, Erkan

2017-11-12

Zinc plays an important role in biological systems as bound and histochemically reactive labile Zn 2+ . Although Zn 2+ concentration is in the nM range in cardiomyocytes at rest and increases dramatically under stimulation, very little is known about precise mechanisms controlling the intracellular distribution of Zn 2+ and its variations during cardiac function. Recent studies are focused on molecular and cellular aspects of labile Zn 2+ and its homeostasis in mammalian cells and growing evidence clarified the molecular mechanisms underlying Zn 2+ -diverse functions in the heart, leading to the discovery of novel physiological functions of labile Zn 2+ in parallel to the discovery of subcellular localization of Zn 2+ -transporters in cardiomyocytes. Additionally, important experimental data suggest a central role of intracellular labile Zn 2+ in excitation-contraction coupling in cardiomyocytes by shaping Ca 2+ dynamics. Cellular labile Zn 2+ is tightly regulated against its adverse effects through either Zn 2+ -transporters, Zn 2+ -binding molecules or Zn 2+ -sensors, and, therefore plays a critical role in cellular signaling pathways. The present review summarizes the current understanding of the physiological role of cellular labile Zn 2+ distribution in cardiomyocytes and how a remodeling of cellular Zn 2+ -homeostasis can be important in proper cell function with Zn 2+ -transporters under hyperglycemia. We also emphasize the recent investigations on Zn 2+ -transporter functions from the standpoint of human heart health to diseases together with their clinical interest as target proteins in the heart under pathological condition, such as diabetes.

Role of intestinal microbiota in the development of multiple sclerosis.

PubMed

Castillo-Álvarez, F; Marzo-Sola, M E

2017-04-01

Multiple sclerosis (MS) is a demyelinating disease that affects young adults; in that age group, it represents the second leading cause of disability in our setting. Its precise aetiology has not been elucidated, but it is widely accepted to occur in genetically predisposed patients who are exposed to certain environmental factors. The discovery of the regulatory role played by intestinal microbiota in various autoimmune diseases has opened a new line of research in this field, which is discussed in this review. We reviewed published studies on the role of the microbiota in the development of both MS and its animal model, experimental autoimmune encephalomyelitis (EAE). In mice, it has been shown that intestinal microorganisms regulate the polarisation of T helper cells from Th1-Th17 up to Th2, the function of regulatory T cells, and the activity of B cells; they participate in the pathogenesis of EAE and contribute to its prevention and treatment. In contrast, evidence in humans is still scarce and mainly based on case-control studies that point to the presence of differences in certain bacterial communities. Multiple evidence points to the role of microbiota in EAE. Extrapolation of these results to MS is still in the early stages of research, and studies are needed to define which bacterial populations are associated with MS, the role they play in pathogenesis, and the therapeutic possibilities this knowledge offers us. Copyright © 2015 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Design, construction, and testing a purpose-built climate-controlled solvent vapor annealing chamber for guided self-assembly of block polymer thin films

NASA Astrophysics Data System (ADS)

Gnabasik, Ryan; Haase, Rustin; Baruth, Andrew

2014-03-01

Despite its efficacy to produce well-ordered, periodic nanostructures, the intricate role multiple parameters play in solvent vapor annealing has not been fully established. In solvent vapor annealing a thin polymer film is exposed to the vapors of a solvent(s) thus forming a swollen and mobile layer to direct the self-assembly process at the nanoscale. Recent developments in both theory and experiment have directly identified critical parameters, but controlling them in any systematic way has proven non-trivial. These identified parameters include vapor pressure, solvent concentration in the film, and, critically, the solvent evaporation rate. To explore their role, a purpose-built solvent vapor annealing chamber was designed and constructed. The all-metal chamber is inert to solvent exposure and pneumatically actuated valves allow for precision timing in the introduction and withdrawal of solvent vapor. Furthermore, the mass flow controlled inlet, chamber pressure gauges, in situ spectral reflectance-based thickness monitoring, and high precision micrometer relief valve, give real-time monitoring and control during the annealing and evaporation phases. Using atomic force microscopy to image the annealed films, we are able to map out the parameter space for a series of polystyrene- b-polylactide (Mn = 75 kg/mol and fPLA = 0.28) block polymer thin films with an intrinsic cylindrical morphology and identify their role in directed assembly. Funded by Creighton University Summer Research Grant.

Purification and partial characterization of analogous 26-kDa rat submandibular and parotid gland integral membrane phosphoproteins that may have a role in exocytosis.

PubMed

Quissell, D O; Deisher, L M

1992-04-01

Rat submandibular and parotid gland exocytosis is primarily controlled by beta-adrenergic receptor stimulation. Although its precise role in the regulation of salivary gland exocytosis is not fully understood, protein phosphorylation, mediated by the activation of cAMP-dependent protein kinase, may be directly involved. Previous studies suggest that analogous 26-kDa integral membrane phosphoproteins may play a direct role in regulating exocytosis. Studies were here undertaken to purify and partially characterize both phosphoproteins. After endogenous phosphorylation with 32P, subcellular fraction and solubilization of the microsomal fraction in n-octyl beta-glucopyranoside, the 26-kDa integral membrane phosphoproteins were purified by high performance liquid chromatography (HPLC), followed by sodium dodecyl sulphate-polyacrylamide gel electrophoresis and electroelution of the proteins. Amino acid analysis indicated a significant number of serine amino acids: N-terminal sequence data demonstrated a high level of homology; and trypsin digestion followed by reversed-phase HPLC indicated the possibility of multiple phosphorylation sites.

Mechanism of SOS PR-domain autoinhibition revealed by single-molecule assays on native protein from lysate

PubMed Central

Lee, Young Kwang; Low-Nam, Shalini T.; Chung, Jean K.; Hansen, Scott D.; Lam, Hiu Yue Monatrice; Alvarez, Steven; Groves, Jay T.

2017-01-01

The guanine nucleotide exchange factor (GEF) Son of Sevenless (SOS) plays a critical role in signal transduction by activating Ras. Here we introduce a single-molecule assay in which individual SOS molecules are captured from raw cell lysate using Ras-functionalized supported membrane microarrays. This enables characterization of the full-length SOS protein, which has not previously been studied in reconstitution due to difficulties in purification. Our measurements on the full-length protein reveal a distinct role of the C-terminal proline-rich (PR) domain to obstruct the engagement of allosteric Ras independently of the well-known N-terminal domain autoinhibition. This inhibitory role of the PR domain limits Grb2-independent recruitment of SOS to the membrane through binding of Ras·GTP in the SOS allosteric binding site. More generally, this assay strategy enables characterization of the functional behaviour of GEFs with single-molecule precision but without the need for purification. PMID:28452363

Mechanism of SOS PR-domain autoinhibition revealed by single-molecule assays on native protein from lysate.

PubMed

Lee, Young Kwang; Low-Nam, Shalini T; Chung, Jean K; Hansen, Scott D; Lam, Hiu Yue Monatrice; Alvarez, Steven; Groves, Jay T

2017-04-28

The guanine nucleotide exchange factor (GEF) Son of Sevenless (SOS) plays a critical role in signal transduction by activating Ras. Here we introduce a single-molecule assay in which individual SOS molecules are captured from raw cell lysate using Ras-functionalized supported membrane microarrays. This enables characterization of the full-length SOS protein, which has not previously been studied in reconstitution due to difficulties in purification. Our measurements on the full-length protein reveal a distinct role of the C-terminal proline-rich (PR) domain to obstruct the engagement of allosteric Ras independently of the well-known N-terminal domain autoinhibition. This inhibitory role of the PR domain limits Grb2-independent recruitment of SOS to the membrane through binding of Ras·GTP in the SOS allosteric binding site. More generally, this assay strategy enables characterization of the functional behaviour of GEFs with single-molecule precision but without the need for purification.

Galectin-3 in autoimmunity and autoimmune diseases

PubMed Central

de Oliveira, Felipe L; Gatto, Mariele; Bassi, Nicola; Luisetto, Roberto; Ghirardello, Anna; Punzi, Leonardo

2015-01-01

Galectin-3 (gal-3) is a β-galactoside-binding lectin, which regulates cell–cell and extracellular interactions during self/non-self-antigen recognition and cellular activation, proliferation, differentiation, migration and apoptosis. It plays a significant role in cellular and tissue pathophysiology by organizing niches that drive inflammation and immune responses. Gal-3 has some therapeutic potential in several diseases, including chronic inflammatory disorders, cancer and autoimmune diseases. Gal-3 exerts a broad spectrum of functions which differs according to its intra- or extracellular localization. Recombinant gal-3 strategy has been used to identify potential mode of action of gal-3; however, exogenous gal-3 may not reproduce the functions of the endogenous gal-3. Notably, gal-3 induces monocyte–macrophage differentiation, interferes with dendritic cell fate decision, regulates apoptosis on T lymphocytes and inhibits B-lymphocyte differentiation into immunoglobulin secreting plasma cells. Considering the influence of these cell populations in the pathogenesis of several autoimmune diseases, gal-3 seems to play a role in development of autoimmunity. Gal-3 has been suggested as a potential therapeutic agent in patients affected with some autoimmune disorders. However, the precise role of gal-3 in driving the inflammatory process in autoimmune or immune-mediated disorders remains elusive. Here, we reviewed the involvement of gal-3 in cellular and tissue events during autoimmune and immune-mediated inflammatory diseases. PMID:26142116

Communication-dependent mineralization of osteoblasts via gap junctions.

PubMed

Hashida, Yukihiko; Nakahama, Ken-ichi; Shimizu, Kaori; Akiyama, Masako; Harada, Kiyoshi; Morita, Ikuo

2014-04-01

Connexin43 (Cx43) is a major gap junction (GJ) protein in bone and plays a critical role in osteoblast differentiation. Several studies show that osteoblast differentiation is delayed by Cx43 ablation. However, the precise mechanism underlying the role of Cx43 in osteoblast differentiation is not fully understood. Firstly, we analyzed the phenotype of a conditional knockout mouse, which was generated by mating of an osterix promoter-driven Cre expressing mouse with a Cx43-floxed mouse. As expected, delayed ossification was observed. Secondly, we demonstrated that the cell communication via gap junctions played an important role in osteoblast differentiation using a tamoxifen-inducible knockout system in vitro. Genetic ablation of Cx43 resulted in both the disruption of cell-communications and the attenuation of osteoblast mineralization induced by BMP-2, but not by ascorbic acid. Moreover, restoring full-length Cx43 (382aa) expression rescued the impairment of osteoblast cell-communication and osteoblast mineralization; however, the expression of the Cx43 N-terminal mutant (382aaG2V) did not rescue either of them. Comparing the gene expression profiles, the genes directly regulated by BMP-2 were attenuated by Cx43 gene ablation. These results suggested that the cell-communication mediated by gap junctions was indispensable for normal differentiation of osteoblast induced by BMP-2. Copyright © 2013 Elsevier Inc. All rights reserved.

Decreased Vδ2 γδ T cells associated with liver damage by regulation of Th17 response in patients with chronic hepatitis B.

PubMed

Wu, Xiaoli; Zhang, Ji-Yuan; Huang, Ang; Li, Yuan-Yuan; Zhang, Song; Wei, Jun; Xia, Siyuan; Wan, Yajuan; Chen, Weiwei; Zhang, Zheng; Li, Yangguang; Wen, Ti; Chen, Yan; Tanaka, Yoshimasa; Cao, Youjia; Wang, Puyue; Zhao, Liqing; Wu, Zhenzhou; Wang, Fu-Sheng; Yin, Zhinan

2013-10-15

 γδ T cells comprise a small subset of T cells and play a protective role against cancer and viral infections; however, their precise role in patients with chronic hepatitis B remains unclear.  Flow cytometry and immunofunctional assays were performed to analyze the impact of Vδ2 γδ (Vδ2) T cells in 64 immune-activated patients, 22 immune-tolerant carriers, and 30 healthy controls.  The frequencies of peripheral and hepatic Vδ2 T cells decreased with disease progression from immune tolerant to immune activated. In the latter group of patients, the decreases in peripheral and intrahepatic frequencies of Vδ2 T cells reversely correlated with alanine aminotransferase levels and histological activity index. These activated terminally differentiated memory phenotypic Vδ2 T cells exhibited impaired abilities in proliferation and chemotaxis, while maintained a relative intact interferon (IFN) γ production. Importantly, Vδ2 T cells, in vitro, significantly suppressed the production of cytokines associated with interleukin 17-producing CD4+ T (Th17) cells through both cell contact-dependent and IFN-γ-dependent mechanisms.  Inflammatory microenvironment in IA patients result in decreased numbers of Vδ2 T cells, which play a novel role by regulating the pathogenic Th17 response to protect the liver in patients with chronic hepatitis B.

TGF-ß Regulates Enamel Mineralization and Maturation through KLK4 Expression

PubMed Central

Cho, Andrew; Haruyama, Naoto; Hall, Bradford; Danton, Mary Jo S.; Zhang, Lu; Arany, Praveen; Mooney, David J.; Harichane, Yassine; Goldberg, Michel; Gibson, Carolyn W.; Kulkarni, Ashok B.

2013-01-01

Transforming growth factor-ß (TGF-ß) signaling plays an important role in regulating crucial biological processes such as cell proliferation, differentiation, apoptosis, and extracellular matrix remodeling. Many of these processes are also an integral part of amelogenesis. In order to delineate a precise role of TGF-ß signaling during amelogenesis, we developed a transgenic mouse line that harbors bovine amelogenin promoter-driven Cre recombinase, and bred this line with TGF-ß receptor II floxed mice to generate ameloblast-specific TGF-ß receptor II conditional knockout (cKO) mice. Histological analysis of the teeth at postnatal day 7 (P7) showed altered enamel matrix composition in the cKO mice as compared to the floxed mice that had enamel similar to the wild-type mice. The µCT and SEM analyses revealed decreased mineral content in the cKO enamel concomitant with increased attrition and thinner enamel crystallites. Although the mRNA levels remained unaltered, immunostaining revealed increased amelogenin, ameloblastin, and enamelin localization in the cKO enamel at the maturation stage. Interestingly, KLK4 mRNA levels were significantly reduced in the cKO teeth along with a slight increase in MMP-20 levels, suggesting that normal enamel maturation is regulated by TGF-ß signaling through the expression of KLK4. Thus, our study indicates that TGF-ß signaling plays an important role in ameloblast functions and enamel maturation. PMID:24278477

Consensus Paper: Roles of the Cerebellum in Motor Control—The Diversity of Ideas on Cerebellar Involvement in Movement

PubMed Central

Bower, James M.; Conforto, Adriana Bastos; Delgado-García, José M.; da Guarda, Suzete Nascimento Farias; Gerwig, Marcus; Habas, Christophe; Hagura, Nobuhiro; Ivry, Richard B.; Mariën, Peter; Molinari, Marco; Naito, Eiichi; Nowak, Dennis A.; Ben Taib, Nordeyn Oulad; Pelisson, Denis; Tesche, Claudia D.; Tilikete, Caroline; Timmann, Dagmar

2015-01-01

Considerable progress has been made in developing models of cerebellar function in sensorimotor control, as well as in identifying key problems that are the focus of current investigation. In this consensus paper, we discuss the literature on the role of the cerebellar circuitry in motor control, bringing together a range of different viewpoints. The following topics are covered: oculomotor control, classical conditioning (evidence in animals and in humans), cerebellar control of motor speech, control of grip forces, control of voluntary limb movements, timing, sensorimotor synchronization, control of corticomotor excitability, control of movement-related sensory data acquisition, cerebro-cerebellar interaction in visuokinesthetic perception of hand movement, functional neuroimaging studies, and magnetoencephalographic mapping of cortico-cerebellar dynamics. While the field has yet to reach a consensus on the precise role played by the cerebellum in movement control, the literature has witnessed the emergence of broad proposals that address cerebellar function at multiple levels of analysis. This paper highlights the diversity of current opinion, providing a framework for debate and discussion on the role of this quintessential vertebrate structure. PMID:22161499

Estimating lava volume by precision combination of multiple baseline spaceborne and airborne interferometric synthetic aperture radar: The 1997 eruption of Okmok Volcano, Alaska

USGS Publications Warehouse

Lu, Z.; Fielding, E.; Patrick, M.R.; Trautwein, C.M.

2003-01-01

Interferometric synthetic aperture radar (InSAR) techniques are used to calculate the volume of extrusion at Okmok volcano, Alaska by constructing precise digital elevation models (DEMs) that represent volcano topography before and after the 1997 eruption. The posteruption DEM is generated using airborne topographic synthetic aperture radar (TOPSAR) data where a three-dimensional affine transformation is used to account for the misalignments between different DEM patches. The preeruption DEM is produced using repeat-pass European Remote Sensing satellite data; multiple interferograms are combined to reduce errors due to atmospheric variations, and deformation rates are estimated independently and removed from the interferograms used for DEM generation. The extrusive flow volume associated with the 1997 eruption of Okmok volcano is 0.154 ?? 0.025 km3. The thickest portion is approximately 50 m, although field measurements of the flow margin's height do not exceed 20 m. The in situ measurements at lava edges are not representative of the total thickness, and precise DEM data are absolutely essential to calculate eruption volume based on lava thickness estimations. This study is an example that demonstrates how InSAR will play a significant role in studying volcanoes in remote areas.

A Novel Zero Velocity Interval Detection Algorithm for Self-Contained Pedestrian Navigation System with Inertial Sensors

PubMed Central

Tian, Xiaochun; Chen, Jiabin; Han, Yongqiang; Shang, Jianyu; Li, Nan

2016-01-01

Zero velocity update (ZUPT) plays an important role in pedestrian navigation algorithms with the premise that the zero velocity interval (ZVI) should be detected accurately and effectively. A novel adaptive ZVI detection algorithm based on a smoothed pseudo Wigner–Ville distribution to remove multiple frequencies intelligently (SPWVD-RMFI) is proposed in this paper. The novel algorithm adopts the SPWVD-RMFI method to extract the pedestrian gait frequency and to calculate the optimal ZVI detection threshold in real time by establishing the function relationships between the thresholds and the gait frequency; then, the adaptive adjustment of thresholds with gait frequency is realized and improves the ZVI detection precision. To put it into practice, a ZVI detection experiment is carried out; the result shows that compared with the traditional fixed threshold ZVI detection method, the adaptive ZVI detection algorithm can effectively reduce the false and missed detection rate of ZVI; this indicates that the novel algorithm has high detection precision and good robustness. Furthermore, pedestrian trajectory positioning experiments at different walking speeds are carried out to evaluate the influence of the novel algorithm on positioning precision. The results show that the ZVI detected by the adaptive ZVI detection algorithm for pedestrian trajectory calculation can achieve better performance. PMID:27669266

Cosmological neutrino simulations at extreme scale

DOE PAGES

Emberson, J. D.; Yu, Hao-Ran; Inman, Derek; ...

2017-08-01

Constraining neutrino mass remains an elusive challenge in modern physics. Precision measurements are expected from several upcoming cosmological probes of large-scale structure. Achieving this goal relies on an equal level of precision from theoretical predictions of neutrino clustering. Numerical simulations of the non-linear evolution of cold dark matter and neutrinos play a pivotal role in this process. We incorporate neutrinos into the cosmological N-body code CUBEP3M and discuss the challenges associated with pushing to the extreme scales demanded by the neutrino problem. We highlight code optimizations made to exploit modern high performance computing architectures and present a novel method ofmore » data compression that reduces the phase-space particle footprint from 24 bytes in single precision to roughly 9 bytes. We scale the neutrino problem to the Tianhe-2 supercomputer and provide details of our production run, named TianNu, which uses 86% of the machine (13,824 compute nodes). With a total of 2.97 trillion particles, TianNu is currently the world’s largest cosmological N-body simulation and improves upon previous neutrino simulations by two orders of magnitude in scale. We finish with a discussion of the unanticipated computational challenges that were encountered during the TianNu runtime.« less

Hydrogels for precision meniscus tissue engineering: a comprehensive review.

PubMed

Rey-Rico, Ana; Cucchiarini, Magali; Madry, Henning

The meniscus plays a pivotal role to preserve the knee joint homeostasis. Lesions to the meniscus are frequent, have a reduced ability to heal, and may induce tibiofemoral osteoarthritis. Current reconstructive therapeutic options mainly focus on the treatment of lesions in the peripheral vascularized region. In contrast, few approaches are capable of stimulating repair of damaged meniscal tissue in the central, avascular portion. Tissue engineering approaches are of high interest to repair or replace damaged meniscus tissue in this area. Hydrogel-based biomaterials are of special interest for meniscus repair as its inner part contains relatively high proportions of proteoglycans which are responsible for the viscoelastic compressive properties and hydration grade. Hydrogels exhibiting high water content and providing a specific three-dimensional (3D) microenvironment may be engineered to precisely resemble this topographical composition of the meniscal tissue. Different polymers of both natural and synthetic origins have been manipulated to produce hydrogels hosting relevant cell populations for meniscus regeneration and provide platforms for meniscus tissue replacement. So far, these compounds have been employed to design controlled delivery systems of bioactive molecules involved in meniscal reparative processes or to host genetically modified cells as a means to enhance meniscus repair. This review describes the most recent advances on the use of hydrogels as platforms for precision meniscus tissue engineering.

Precise predictions for V+jets dark matter backgrounds

NASA Astrophysics Data System (ADS)

Lindert, J. M.; Pozzorini, S.; Boughezal, R.; Campbell, J. M.; Denner, A.; Dittmaier, S.; Gehrmann-De Ridder, A.; Gehrmann, T.; Glover, N.; Huss, A.; Kallweit, S.; Maierhöfer, P.; Mangano, M. L.; Morgan, T. A.; Mück, A.; Petriello, F.; Salam, G. P.; Schönherr, M.; Williams, C.

2017-12-01

High-energy jets recoiling against missing transverse energy (MET) are powerful probes of dark matter at the LHC. Searches based on large MET signatures require a precise control of the Z(ν {\\bar{ν }})+ jet background in the signal region. This can be achieved by taking accurate data in control regions dominated by Z(ℓ ^+ℓ ^-)+ jet, W(ℓ ν )+ jet and γ + jet production, and extrapolating to the Z(ν {\\bar{ν }})+ jet background by means of precise theoretical predictions. In this context, recent advances in perturbative calculations open the door to significant sensitivity improvements in dark matter searches. In this spirit, we present a combination of state-of-the-art calculations for all relevant V+ jets processes, including throughout NNLO QCD corrections and NLO electroweak corrections supplemented by Sudakov logarithms at two loops. Predictions at parton level are provided together with detailed recommendations for their usage in experimental analyses based on the reweighting of Monte Carlo samples. Particular attention is devoted to the estimate of theoretical uncertainties in the framework of dark matter searches, where subtle aspects such as correlations across different V+ jet processes play a key role. The anticipated theoretical uncertainty in the Z(ν {\\bar{ν }})+ jet background is at the few percent level up to the TeV range.

Outlier analysis of functional genomic profiles enriches for oncology targets and enables precision medicine.

PubMed

Zhu, Zhou; Ihle, Nathan T; Rejto, Paul A; Zarrinkar, Patrick P

2016-06-13

Genome-scale functional genomic screens across large cell line panels provide a rich resource for discovering tumor vulnerabilities that can lead to the next generation of targeted therapies. Their data analysis typically has focused on identifying genes whose knockdown enhances response in various pre-defined genetic contexts, which are limited by biological complexities as well as the incompleteness of our knowledge. We thus introduce a complementary data mining strategy to identify genes with exceptional sensitivity in subsets, or outlier groups, of cell lines, allowing an unbiased analysis without any a priori assumption about the underlying biology of dependency. Genes with outlier features are strongly and specifically enriched with those known to be associated with cancer and relevant biological processes, despite no a priori knowledge being used to drive the analysis. Identification of exceptional responders (outliers) may not lead only to new candidates for therapeutic intervention, but also tumor indications and response biomarkers for companion precision medicine strategies. Several tumor suppressors have an outlier sensitivity pattern, supporting and generalizing the notion that tumor suppressors can play context-dependent oncogenic roles. The novel application of outlier analysis described here demonstrates a systematic and data-driven analytical strategy to decipher large-scale functional genomic data for oncology target and precision medicine discoveries.

Integrative Analysis of Transcription Factor Combinatorial Interactions Using a Bayesian Tensor Factorization Approach

PubMed Central

Ye, Yusen; Gao, Lin; Zhang, Shihua

2017-01-01

Transcription factors play a key role in transcriptional regulation of genes and determination of cellular identity through combinatorial interactions. However, current studies about combinatorial regulation is deficient due to lack of experimental data in the same cellular environment and extensive existence of data noise. Here, we adopt a Bayesian CANDECOMP/PARAFAC (CP) factorization approach (BCPF) to integrate multiple datasets in a network paradigm for determining precise TF interaction landscapes. In our first application, we apply BCPF to integrate three networks built based on diverse datasets of multiple cell lines from ENCODE respectively to predict a global and precise TF interaction network. This network gives 38 novel TF interactions with distinct biological functions. In our second application, we apply BCPF to seven types of cell type TF regulatory networks and predict seven cell lineage TF interaction networks, respectively. By further exploring the dynamics and modularity of them, we find cell lineage-specific hub TFs participate in cell type or lineage-specific regulation by interacting with non-specific TFs. Furthermore, we illustrate the biological function of hub TFs by taking those of cancer lineage and blood lineage as examples. Taken together, our integrative analysis can reveal more precise and extensive description about human TF combinatorial interactions. PMID:29033978

Integrative Analysis of Transcription Factor Combinatorial Interactions Using a Bayesian Tensor Factorization Approach.

PubMed

Ye, Yusen; Gao, Lin; Zhang, Shihua

2017-01-01

Transcription factors play a key role in transcriptional regulation of genes and determination of cellular identity through combinatorial interactions. However, current studies about combinatorial regulation is deficient due to lack of experimental data in the same cellular environment and extensive existence of data noise. Here, we adopt a Bayesian CANDECOMP/PARAFAC (CP) factorization approach (BCPF) to integrate multiple datasets in a network paradigm for determining precise TF interaction landscapes. In our first application, we apply BCPF to integrate three networks built based on diverse datasets of multiple cell lines from ENCODE respectively to predict a global and precise TF interaction network. This network gives 38 novel TF interactions with distinct biological functions. In our second application, we apply BCPF to seven types of cell type TF regulatory networks and predict seven cell lineage TF interaction networks, respectively. By further exploring the dynamics and modularity of them, we find cell lineage-specific hub TFs participate in cell type or lineage-specific regulation by interacting with non-specific TFs. Furthermore, we illustrate the biological function of hub TFs by taking those of cancer lineage and blood lineage as examples. Taken together, our integrative analysis can reveal more precise and extensive description about human TF combinatorial interactions.

Towards precision medicine: from quantitative imaging to radiomics

PubMed Central

Acharya, U. Rajendra; Hagiwara, Yuki; Sudarshan, Vidya K.; Chan, Wai Yee; Ng, Kwan Hoong

2018-01-01

Radiology (imaging) and imaging-guided interventions, which provide multi-parametric morphologic and functional information, are playing an increasingly significant role in precision medicine. Radiologists are trained to understand the imaging phenotypes, transcribe those observations (phenotypes) to correlate with underlying diseases and to characterize the images. However, in order to understand and characterize the molecular phenotype (to obtain genomic information) of solid heterogeneous tumours, the advanced sequencing of those tissues using biopsy is required. Thus, radiologists image the tissues from various views and angles in order to have the complete image phenotypes, thereby acquiring a huge amount of data. Deriving meaningful details from all these radiological data becomes challenging and raises the big data issues. Therefore, interest in the application of radiomics has been growing in recent years as it has the potential to provide significant interpretive and predictive information for decision support. Radiomics is a combination of conventional computer-aided diagnosis, deep learning methods, and human skills, and thus can be used for quantitative characterization of tumour phenotypes. This paper discusses the overview of radiomics workflow, the results of various radiomics-based studies conducted using various radiological images such as computed tomography (CT), magnetic resonance imaging (MRI), and positron-emission tomography (PET), the challenges we are facing, and the potential contribution of radiomics towards precision medicine. PMID:29308604

Integrating three-dimensional digital technologies for comprehensive implant dentistry.

PubMed

Patel, Neal

2010-06-01

The increase in the popularity of and the demand for the use of dental implants to replace teeth has encouraged advancement in clinical technology and materials to improve patients' acceptance and clinical outcomes. Recent advances such as three-dimensional dental radiography with cone-beam computed tomography (CBCT), precision dental implant planning software and clinical execution with guided surgery all play a role in the success of implant dentistry. The author illustrates the technique of comprehensive implant dentistry planning through integration of computer-aided design/computer-aided manufacturing (CAD/CAM) and CBCT data. The technique includes clinical treatment with guided surgery, including the creation of a final restoration with a high-strength ceramic (IPS e.max CAD, Ivoclar Vivadent, Amherst, N.Y.). The author also introduces a technique involving CAD/CAM for fabricating custom implant abutments. The release of software integrating CEREC Acquisition Center with Bluecam (Sirona Dental Systems, Charlotte, N.C.) chairside CAD/CAM and Galileos CBCT imaging (Sirona Dental Systems) allows dentists to plan implant placement, perform implant dentistry with increased precision and provide predictable restorative results by using chairside IPS e.max CAD. The precision of clinical treatment provided by the integration of CAD/CAM and CBCT allows dentists to plan for ideal surgical placement and the appropriate thickness of restorative modalities before placing implants.

Synchronized motion control and precision positioning compensation of a 3-DOFs macro-micro parallel manipulator fully actuated by piezoelectric actuators

NASA Astrophysics Data System (ADS)

Zhang, Quan; Li, Chaodong; Zhang, Jiantao; Zhang, Xu

2017-11-01

The macro-micro combined approach, as an effective way to realize trans-scale nano-precision positioning with multi-dimensions and high velocity, plays a significant role in integrated circuit manufacturing field. A 3-degree-of-freedoms (3-DOFs) macro-micro manipulator is designed and analyzed to compromise the conflictions among the large stroke, high precision and multi-DOFs. The macro manipulator is a 3-Prismatic-Revolute-Revolute (3-PRR) structure parallel manipulator which is driven by three linear ultrasonic motors. The dynamic model and the cross-coupling error based synchronized motion controller of the 3-PRR parallel manipulator are theoretical analyzed and experimental tested. To further improve the positioning accuracy, a 3-DOFs monolithic compliant manipulator actuated by three piezoelectric stack actuators is designed. Then a multilayer BP neural network based inverse kinematic model identifier is developed to perform the positioning control. Finally, by forming the macro-micro structure, the dual stage manipulator successfully achieved the positioning task from the point (2 mm, 2 mm, 0 rad) back to the original point (0 mm, 0 mm, 0 rad) with the translation errors in X and Y directions less than ±50 nm and the rotation error around Z axis less than ±1 μrad, respectively.

A Self-Organizing Spatial Clustering Approach to Support Large-Scale Network RTK Systems.

PubMed

Shen, Lili; Guo, Jiming; Wang, Lei

2018-06-06

The network real-time kinematic (RTK) technique can provide centimeter-level real time positioning solutions and play a key role in geo-spatial infrastructure. With ever-increasing popularity, network RTK systems will face issues in the support of large numbers of concurrent users. In the past, high-precision positioning services were oriented towards professionals and only supported a few concurrent users. Currently, precise positioning provides a spatial foundation for artificial intelligence (AI), and countless smart devices (autonomous cars, unmanned aerial-vehicles (UAVs), robotic equipment, etc.) require precise positioning services. Therefore, the development of approaches to support large-scale network RTK systems is urgent. In this study, we proposed a self-organizing spatial clustering (SOSC) approach which automatically clusters online users to reduce the computational load on the network RTK system server side. The experimental results indicate that both the SOSC algorithm and the grid algorithm can reduce the computational load efficiently, while the SOSC algorithm gives a more elastic and adaptive clustering solution with different datasets. The SOSC algorithm determines the cluster number and the mean distance to cluster center (MDTCC) according to the data set, while the grid approaches are all predefined. The side-effects of clustering algorithms on the user side are analyzed with real global navigation satellite system (GNSS) data sets. The experimental results indicate that 10 km can be safely used as the cluster radius threshold for the SOSC algorithm without significantly reducing the positioning precision and reliability on the user side.

Functional sensibility assessment. Part II: Effects of sensory improvement on precise pinch force modulation after transverse carpal tunnel release.

PubMed

Hsu, Hsiu-Yun; Kuo, Li-Chieh; Chiu, Haw-Yen; Jou, I-Ming; Su, Fong-Chin

2009-11-01

Patients with median nerve compression at the carpal tunnel often have poor sensory afferents. Without adequate sensory modulation control, these patients frequently exhibit clumsy performance and excessive force output in the affected hand. We analyzed precision grip function after the sensory recovery of patients with carpal tunnel syndrome (CTS) who underwent carpal tunnel release (CTR). Thirteen CTS patients were evaluated using a custom-designed pinch device and conventional sensory tools before and after CTR to measure sensibility, maximum pinch strength, and anticipated pinch force adjustments to movement-induced load fluctuations in a pinch-holding-up activity. Based on these tests, five force-related parameters and sensory measurements were used to determine improvements in pinch performance after sensory recovery. The force ratio between the exerted pinch force and maximum load force of the lifting object was used to determine pinch force coordination and to prove that CTR enabled precision motor output. The magnitude of peak pinch force indicated an economic force output during manipulations following CTR. The peak pinch force, force ratio, and percentage of maximum pinch force also demonstrated a moderate correlation with the Semmes-Weinstein test. Analysis of these tests revealed that improved sensory function helped restore patients' performance in precise pinch force control evaluations. These results suggest that sensory information plays an important role in adjusting balanced force output in dexterous manipulation. (c) 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

A Skilful Marine Sclerochronological Network Based Reconstruction of North Atlantic Subpolar Gyre Dynamics

NASA Astrophysics Data System (ADS)

Reynolds, D.; Hall, I. R.; Slater, S. M.; Scourse, J. D.; Wanamaker, A. D.; Halloran, P. R.; Garry, F. K.

2017-12-01

Spatial network analyses of precisely dated, and annually resolved, tree-ring proxy records have facilitated robust reconstructions of past atmospheric climate variability and the associated mechanisms and forcings that drive it. In contrast, a lack of similarly dated marine archives has constrained the use of such techniques in the marine realm, despite the potential for developing a more robust understanding of the role basin scale ocean dynamics play in the global climate system. Here we show that a spatial network of marine molluscan sclerochronological oxygen isotope (δ18Oshell) series spanning the North Atlantic region provides a skilful reconstruction of basin scale North Atlantic sea surface temperatures (SSTs). Our analyses demonstrate that the composite marine series (referred to as δ18Oproxy_PC1) is significantly sensitive to inter-annual variability in North Atlantic SSTs (R=-0.61 P<0.01) and surface air temperatures (SATs; R=-0.67, P<0.01) over the 20th century. Subpolar gyre (SPG) SSTs dominates variability in the δ18Oproxy_PC1 series at sub-centennial frequencies (R=-0.51, P<0.01). Comparison of the δ18Oproxy_PC1 series against variability in the strength of the European Slope Current and maximum North Atlantic meridional overturning circulation derived from numeric climate models (CMIP5), indicates that variability in the SPG region, associated with the strength of the surface currents of the North Atlantic, are playing a significant role in shaping the multi-decadal scale SST variability over the industrial era. These analyses demonstrate that spatial networks developed from sclerochronological archives can provide powerful baseline archives of past ocean variability that can facilitate the development of a quantitative understanding for the role the oceans play in the global climate systems and constraining uncertainties in numeric climate models.

Transcriptome Profiling Identifies Multiplexin as a Target of SAGA Deubiquitinase Activity in Glia Required for Precise Axon Guidance During Drosophila Visual Development.

PubMed

Ma, Jingqun; Brennan, Kaelan J; D'Aloia, Mitch R; Pascuzzi, Pete E; Weake, Vikki M

2016-08-09

The Spt-Ada-Gcn5 Acetyltransferase (SAGA) complex is a transcriptional coactivator with histone acetylase and deubiquitinase activities that plays an important role in visual development and function. In Drosophila melanogaster, four SAGA subunits are required for the deubiquitination of monoubiquitinated histone H2B (ubH2B): Nonstop, Sgf11, E(y)2, and Ataxin 7. Mutations that disrupt SAGA deubiquitinase activity cause defects in neuronal connectivity in the developing Drosophila visual system. In addition, mutations in SAGA result in the human progressive visual disorder spinocerebellar ataxia type 7 (SCA7). Glial cells play a crucial role in both the neuronal connectivity defect in nonstop and sgf11 flies, and in the retinal degeneration observed in SCA7 patients. Thus, we sought to identify the gene targets of SAGA deubiquitinase activity in glia in the Drosophila larval central nervous system. To do this, we enriched glia from wild-type, nonstop, and sgf11 larval optic lobes using affinity-purification of KASH-GFP tagged nuclei, and then examined each transcriptome using RNA-seq. Our analysis showed that SAGA deubiquitinase activity is required for proper expression of 16% of actively transcribed genes in glia, especially genes involved in proteasome function, protein folding and axon guidance. We further show that the SAGA deubiquitinase-activated gene Multiplexin (Mp) is required in glia for proper photoreceptor axon targeting. Mutations in the human ortholog of Mp, COL18A1, have been identified in a family with a SCA7-like progressive visual disorder, suggesting that defects in the expression of this gene in SCA7 patients could play a role in the retinal degeneration that is unique to this ataxia. Copyright © 2016 Ma et al.

Massive stellar systems: observational challenges and perspectives in the E-ELT era

NASA Astrophysics Data System (ADS)

Bono, G.; Braga, V. F.; Ferraro, I.; Fiorentino, G.; Gilmozzi, R.; Iannicola, G.; Magurno, D.; Matsunaga, N.; Monelli, M.; Rastello, S.

2017-03-01

We introduce the empirical framework concerning optical and near-infrared (NIR) photometry of crowded stellar fields. In particular, we address the impact that linear detectors and analytical PSF played in improving the accuracy and the precision of multi-band color-magnitude diagrams (CMDs). We focus our attention on recent findings based on deep NIR images collected with Adaptive Optics (AO) systems at the 8-10m class telescopes and discuss pros and cons of the different approaches. We also discuss the estimate of the absolute age of globular clusters using a well defined knee along the lower main sequence. We mention the role which the current AO-assisted instruments will have in addressing longstanding astrophysical problems of the Galactic center. Finally, we outline the role of first generation of E-ELT instruments upon photometry and spectroscopy of crowded stellar fields.

The role of molecular hydrogen and methane oxidation in the water vapour budget of the stratosphere

NASA Technical Reports Server (NTRS)

Le Texier, H.; Solomon, S.; Garcia, R. R.

1988-01-01

The detailed photochemistry of methane oxidation has been studied in a coupled chemical/dynamical model of the middle atmosphere. The photochemistry of formaldehyde plays an important role in determining the production of water vapor from methane oxidation. At high latitudes, the production and transport of molecular hydrogen is particularly important in determining the water vapor distribution. It is shown that the ratio of the methane vertical gradient to the water vapor vertical gradient at any particular latitude should not be expected to be precisely 2, due both to photochemical and dynamical effects. Modeled H2O profiles are compared with measurements from the Limb Infrared Monitor of the Stratosphere (LIMS) experiment at various latitudes. Molecular hydrogen is shown to be responsible for the formation of a secondary maximum displayed by the model water vapor profiles in high latitude summer, a feature also found in the LIMS data.

The role of extreme orbits in the global organization of periodic regions in parameter space for one dimensional maps

NASA Astrophysics Data System (ADS)

da Costa, Diogo Ricardo; Hansen, Matheus; Guarise, Gustavo; Medrano-T, Rene O.; Leonel, Edson D.

2016-04-01

We show that extreme orbits, trajectories that connect local maximum and minimum values of one dimensional maps, play a major role in the parameter space of dissipative systems dictating the organization for the windows of periodicity, hence producing sets of shrimp-like structures. Here we solve three fundamental problems regarding the distribution of these sets and give: (i) their precise localization in the parameter space, even for sets of very high periods; (ii) their local and global distributions along cascades; and (iii) the association of these cascades to complicate sets of periodicity. The extreme orbits are proved to be a powerful indicator to investigate the organization of windows of periodicity in parameter planes. As applications of the theory, we obtain some results for the circle map and perturbed logistic map. The formalism presented here can be extended to many other different nonlinear and dissipative systems.

[Symptomatic urinary tract infection of the female--diagnostics].

PubMed

Bruns, T; Piechota, H; Schneede, P

2006-04-01

The basis for the diagnostic work-up of recurrent cystitis is formed by taking a precise medical history against the background of knowledge of the pathogenesis of urinary tract infections. The anamnesis should also focus on factors that influence the natural flora (sexual intercourse, hygiene) but additionally include preceding antibiotic treatment and diseases that affect the immune status (diabetes mellitus). Urinalysis is the principal examination among the laboratory diagnostic procedures. The diagnosis is promptly confirmed by immediate analysis of a clean catch midstream urine sample using a counting chamber or a test strip. As a matter of principle, microbiological diagnosis always ensues. Extended diagnostic work-up (urological staging) is aimed at detecting functional and anatomic abnormalities. While these factors only play a subordinate role during the premenopausal phase, they gain in importance during the postmenopausal phase. A key role is also attributed to local estrogen deficiency.

Systems analysis of shoot apical meristem growth and development: integrating hormonal and mechanical signaling.

PubMed

Murray, James A H; Jones, Angharad; Godin, Christophe; Traas, Jan

2012-10-01

The shoot apical meristem (SAM) is a small population of stem cells that continuously generates organs and tissues. This review covers our current understanding of organ initiation by the SAM in Arabidopsis thaliana. Meristem function and maintenance involves two major hormones, cytokinins and auxins. Cytokinins appear to play a major role in meristem maintenance and in controlling meristematic properties, such as cell proliferation. Self-organizing transport processes, which are still only partially understood, lead to the patterned accumulation of auxin at particular positions, where organs will grow out. A major downstream target of auxin-mediated growth regulation is the cell wall, which is a determinant for both growth rates and growth distribution, but feedbacks with metabolism and the synthetic capacity of the cytoplasm are crucial as well. Recent work has also pointed at a potential role of mechanical signals in growth coordination, but the precise mechanisms at work remain to be elucidated.

Regulation of neuronal communication by G protein-coupled receptors.

PubMed

Huang, Yunhong; Thathiah, Amantha

2015-06-22

Neuronal communication plays an essential role in the propagation of information in the brain and requires a precisely orchestrated connectivity between neurons. Synaptic transmission is the mechanism through which neurons communicate with each other. It is a strictly regulated process which involves membrane depolarization, the cellular exocytosis machinery, neurotransmitter release from synaptic vesicles into the synaptic cleft, and the interaction between ion channels, G protein-coupled receptors (GPCRs), and downstream effector molecules. The focus of this review is to explore the role of GPCRs and G protein-signaling in neurotransmission, to highlight the function of GPCRs, which are localized in both presynaptic and postsynaptic membrane terminals, in regulation of intrasynaptic and intersynaptic communication, and to discuss the involvement of astrocytic GPCRs in the regulation of neuronal communication. Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Global Precipitation Measurement Program and the Development of Dual-Frequency Precipitation Radar

NASA Technical Reports Server (NTRS)

Iguchi, Toshio; Oki, Riko; Smith, Eric A.; Furuhama, Yoji

2002-01-01

The Global Precipitation Measurement (GPM) program is a mission to measure precipitation from space, and is a similar but much expanded mission of the Tropical Rainfall Measuring Mission. Its scope is not limited to scientific research, but includes practical and operational applications such as weather forecasting and water resource management. To meet the requirements of operational use, the GPM uses multiple low-orbiting satellites to increase the sampling frequency and to create three-hourly global rain maps that will be delivered to the world in quasi-real time. A dual-frequency radar (DPR) will be installed on the primary satellite that plays an important role in the whole mission. The DPR will realize measurement of precipitation with high sensitivity, high precision and high resolutions. This paper describes an outline of the GPM program, its issues and the roles and development of the DPR.

Measuring reactive species and oxidative damage in vivo and in cell culture: how should you do it and what do the results mean?

PubMed Central

Halliwell, Barry; Whiteman, Matthew

2004-01-01

Free radicals and other reactive species (RS) are thought to play an important role in many human diseases. Establishing their precise role requires the ability to measure them and the oxidative damage that they cause. This article first reviews what is meant by the terms free radical, RS, antioxidant, oxidative damage and oxidative stress. It then critically examines methods used to trap RS, including spin trapping and aromatic hydroxylation, with a particular emphasis on those methods applicable to human studies. Methods used to measure oxidative damage to DNA, lipids and proteins and methods used to detect RS in cell culture, especially the various fluorescent ‘probes' of RS, are also critically reviewed. The emphasis throughout is on the caution that is needed in applying these methods in view of possible errors and artifacts in interpreting the results. PMID:15155533

Sampling of atmospheric carbonyl compounds for determination by liquid chromatography after 2,4-dinitrophenylhydrazine labelling

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

Vairavamurthy, A.; Roberts, J.M.; Newman, L.

1991-02-01

Determination of carbonyl compounds in the ambient atmosphere is receiving increasing attention because of the critical role these compounds play as pollutants and as key participants in tropospheric photochemistry. Carbonyls are involved in photochemical reactions as products of the oxidation of hydrocarbons, precursors of oxidants including ozone and peroxycarboxylic nitric anhydrides (PANs), and as sources of free radicals and organic aerosols. A correct understanding and assessment of the role of carbonyls in tropospheric chemistry requires the accurate and precise measurement of these compounds along with their parent and product compounds. Here we discuss some of these important issues along withmore » the different techniques used for time-integrated collection of carbonyls in the DNPH based liquid chromatographic methods because of their complexity, variability and as well their importance; we emphasize the principles, advantages, and limitations of these techniques. 58 refs., 9 figs., 3 tabs.« less

Barium bioaccumulation by bacterial biofilms and implications for Ba cycling and use of Ba proxies.

PubMed

Martinez-Ruiz, Francisca; Jroundi, Fadwa; Paytan, Adina; Guerra-Tschuschke, Isabel; Abad, María Del Mar; González-Muñoz, María Teresa

2018-04-24

Ba proxies have been broadly used to reconstruct past oceanic export production. However, the precise mechanisms underlying barite precipitation in undersaturated seawater are not known. The link between bacterial production and particulate Ba in the ocean suggests that bacteria may play a role. Here we show that under experimental conditions marine bacterial biofilms, particularly extracellular polymeric substances (EPS), are capable of bioaccumulating Ba, providing adequate conditions for barite precipitation. An amorphous P-rich phase is formed at the initial stages of Ba bioaccumulation, which evolves into barite crystals. This supports that in high productivity regions where large amounts of organic matter are subjected to bacterial degradation, the abundant EPS would serve to bind the necessary Ba and form nucleation sites leading to barite precipitation. This also provides new insights into barite precipitation and opens an exciting field to explore the role of EPS in mineral precipitation in the ocean.

Time-sequential observation of spindle and phragmoplast orientation in BY-2 cells with altered cortical actin microfilament patterning.

PubMed

Kojo, Kei H; Yasuhara, Hiroki; Hasezawa, Seiichiro

2014-01-01

Precise division plane determination is essential for plant development. At metaphase, a dense actin microfilament meshwork appears on both sides of the cell center, forming a characteristic cortical actin microfilament twin peak pattern in BY-2 cells. We previously reported a strong correlation between altered cortical actin microfilament patterning and an oblique mitotic spindle orientation, implying that these actin microfilament twin peaks play a role in the regulation of mitotic spindle orientation. In the present study, time-sequential observation was used to reveal the progression from oblique phragmoplast to oblique cell plate orientation in cells with altered cortical actin microfilament patterning. In contrast to cells with normal actin microfilament twin peaks, oblique phragmoplast reorientation was rarely observed in cells with altered cortical actin microfilament patterning. These results support the important roles of cortical actin microfilament patterning in division plane orientation.

Time-sequential observation of spindle and phragmoplast orientation in BY-2 cells with altered cortical actin microfilament patterning.

PubMed

Kojo, Kei H; Yasuhara, Hiroki; Hasezawa, Seiichiro

2014-06-18

Precise division plane determination is essential for plant development. At metaphase, a dense actin microfilament meshwork appears on both sides of the cell center, forming a characteristic cortical actin microfilament twin peak pattern in BY-2 cells. We previously reported a strong correlation between altered cortical actin microfilament patterning and an oblique mitotic spindle orientation, implying that these actin microfilament twin peaks play a role in the regulation of mitotic spindle orientation. In the present study, time-sequential observation was used to reveal the progression from oblique phragmoplast to oblique cell plate orientation in cells with altered cortical actin microfilament patterning. In contrast to cells with normal actin microfilament twin peaks, oblique phragmoplast reorientation was rarely observed in cells with altered cortical actin microfilament patterning. These results support the important roles of cortical actin microfilament patterning in division plane orientation.

Aquaporins in desert rodent physiology.

PubMed

Pannabecker, Thomas L

2015-08-01

Desert rodents face a sizeable challenge in maintaining salt and water homeostasis due to their life in an arid environment. A number of their organ systems exhibit functional characteristics that limit water loss above that which occurs in non-desert species under similar conditions. These systems include renal, pulmonary, gastrointestinal, nasal, and skin epithelia. The desert rodent kidney preserves body water by producing a highly concentrated urine that reaches a maximum osmolality nearly three times that of the common laboratory rat. The precise mechanism by which urine is concentrated in any mammal is unknown. Insights into the process may be more apparent in species that produce highly concentrated urine. Aquaporin water channels play a fundamental role in water transport in several desert rodent organ systems. The role of aquaporins in facilitating highly effective water preservation in desert rodents is only beginning to be explored. The organ systems of desert rodents and their associated AQPs are described. © 2015 Marine Biological Laboratory.

Peroxisome Proliferator-Activated Receptor (PPAR) in Regenerative Medicine: Molecular Mechanism for PPAR in Stem Cells' Adipocyte Differentiation.

PubMed

Xie, Qiang; Tian, Taoran; Chen, Zhaozhao; Deng, Shuwen; Sun, Ke; Xie, Jing; Cai, Xiaoxiao

2016-01-01

Regenerative medicine plays an indispensable role in modern medicine and many trials and researches have therefore been developed to fit our medical needs. Tissue engineering has proven that adipose tissue can widely be used and brings advantages to regenerative medicine. Moreover, a trait of adipose stem cells being isolated and grown in vitro is a cornerstone to various applications. Since the adipose tissue has been widely used in regenerative medicine, numerous studies have been conducted to seek methods for gaining more adipocytes. To investigate molecular mechanism for adipocyte differentiation, peroxisome proliferator-activated receptor (PPAR) has been widely studied to find out its functional mechanism, as a key factor for adipocyte differentiation. However, the precise molecular mechanism is still unknown. This review thus summarizes recent progress on the study of molecular mechanism and role of PPAR in adipocyte differentiation.

Oxytocin mediated behavior in invertebrates: An evolutionary perspective.

PubMed

Lockard, Meghan A; Ebert, Margaret S; Bargmann, Cornelia I

2017-02-01

The molecular and functional conservation of oxytocin-related neuropeptides in behavior is striking. In animals separated by at least 600 million years of evolution, from roundworms to humans, oxytocin homologs play critical roles in the modulation of reproductive behavior and other biological functions. Here, we review the roles of oxytocin in invertebrate behavior from an evolutionary perspective. We begin by tracing the evolution of oxytocin through the invertebrate animal lineages, and then describe common themes in invertebrate behaviors that are mediated by oxytocin-related peptides, including reproductive behavior, learning and memory, food arousal, and predator/prey relationships. Finally, we discuss interesting future directions that have recently become experimentally tractable. Studying oxytocin in invertebrates offers precise insights into the activity of neuropeptides on well-defined neural circuits; the principles that emerge may also be represented in the more complex vertebrate brain. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 77: 128-142, 2017. © 2016 Wiley Periodicals, Inc.

Experiments with probe masses

PubMed Central

Braginsky, V. B.

2007-01-01

It is reasonable to regard the experiments performed by C. Coulomb and H. Cavendish in the end of the 18th century as the beginning of laboratory experimental physics. These outstanding scientists have measured forces (accelerations) produced by electric charges and by gravitational “charges” on probe masses that were attached to torque balance. Among the variety of different research programs and projects existing today, experiments with probe masses are still playing an important role. In this short review, the achieved and planned sensitivities of very challenging LIGO (Laser Interferometer Gravitational wave Observatory) and LISA (Laser Interferometer Space Antennae) projects are described, and a list of nonsolved problems is discussed as well. The role of quantum fluctuations in high precision measurements is also outlined. Apart from these main topics, the limitations of sensitivity caused by cosmic rays and the prospects of clock frequency stability are presented. PMID:17296944

Autophagy as an emerging therapy target for ovarian carcinoma

PubMed Central

Zhan, Lei; Zhang, Yu; Wang, Wenyan; Song, Enxue; Fan, Yijun; Li, Jun; Wei, Bing

2016-01-01

Autophagy is a conserved cellular self-digestion pathway for maintenance of homeostasis under basal and stressed conditions. Autophagy plays pivotal roles in the pathogenesis of many diseases, such as aging-related diseases, autoimmune diseases, cardiovascular diseases, and cancers. Of special note is that accumulating data suggest an intimate relationship between autophagy and ovarian carcinoma. Autophagy is well identified to act as either as a tumor-suppressor or as a tumor-promoter in ovarian carcinoma. The exact function of autophagy in ovarian carcinoma is highly dependent on the circumstances of cancer including hypoxic, nutrient-deficient, chemotherapy and so on. However, the mechanism underlying autophagy associated with ovarian carcinoma remains elusive, the precise role of autophagy in ovarian carcinoma also remains undetermined. In this review, we tried to sum up and discuss recent research achievements of autophagy in ovarian cancer. Moreover, waves of novel therapies ways for ovarian carcinoma based on the functions of autophagy were collected. PMID:27825125

Ubiquitylation and proteasomal degradation of the p21(Cip1), p27(Kip1) and p57(Kip2) CDK inhibitors.

PubMed

Lu, Zhimin; Hunter, Tony

2010-06-15

The expression levels of the p21(Cip1) family CDK inhibitors (CKIs), p21(Cip1), p27(Kip1) and p57(Kip2), play a pivotal role in the precise regulation of cyclin-dependent kinase (CDK) activity, which is instrumental to proper cell cycle progression. The stabilities of p21(Cip1), p27(Kip1) and p57(Kip2) are all tightly and differentially regulated by ubiquitylation and proteasome-mediated degradation during various stages of the cell cycle, either in steady state or in response to extracellular stimuli, which often elicit site-specific phosphorylation of CKIs triggering their degradation.

Review of microfluidic cell culture devices for the control of gaseous microenvironments in vitro

NASA Astrophysics Data System (ADS)

Wu, H.-M.; Lee, T.-A.; Ko, P.-L.; Chiang, H.-J.; Peng, C.-C.; Tung, Y.-C.

2018-04-01

Gaseous microenvironments play important roles in various biological activities in vivo. However, it is challenging to precisely control gaseous microenvironments in vitro for cell culture due to the high diffusivity nature of gases. In recent years, microfluidics has paved the way for the development of new types of cell culture devices capable of manipulating cellular microenvironments, and provides a powerful tool for in vitro cell studies. This paper reviews recent developments of microfluidic cell culture devices for the control of gaseous microenvironments, and discusses the advantages and limitations of current devices. We conclude with suggestions for the future development of microfluidic cell culture devices for the control of gaseous microenvironments.

Global well-posedness of three-dimensional Navier-Stokes equations with partial viscosity under helical symmetry

NASA Astrophysics Data System (ADS)

Liu, Jitao; Niu, Dongjuan

2017-06-01

In this paper, we investigate the global well-posedness of three-dimensional Navier-Stokes equations with horizontal viscosity under a special symmetric structure: helical symmetry. More precisely, by a revised Ladyzhenskaya-type inequality and utilizing the behavior of helical flows, we prove the global existence and uniqueness of weak and strong solutions to the three-dimensional helical flows. Our result reveals that for the issue of global well-posedness of the viscous helical flows, the horizontal viscosity plays the important role. To some extent, our work can be seen as a generalization of the result by Mahalov et al. (Arch Ration Mech Anal 112(3):193-222, 1990).

Research on dynamic characteristics of motor vibration isolation system through mechanical impedance method

NASA Astrophysics Data System (ADS)

Zhao, Xingqian; Xu, Wei; Shuai, Changgeng; Hu, Zechao

2017-12-01

A mechanical impedance model of a coupled motor-shaft-bearing system has been developed to predict the dynamic characteristics and partially validated by comparing the computing results with finite element method (FEM), including the comparison of displacement amplitude in x and z directions at the two ends of the flexible coupling, the comparison of normalized vertical reaction force in z direction at bearing pedestals. The results demonstrate that the developed model can precisely predict the dynamic characteristics and the main advantage of such a method is that it can clearly illustrate the vibration property of the motor subsystem, which plays an important role in the isolation system design.

Applications of neural network methods to the processing of earth observation satellite data.

PubMed

Loyola, Diego G

2006-03-01

The new generation of earth observation satellites carries advanced sensors that will gather very precise data for studying the Earth system and global climate. This paper shows that neural network methods can be successfully used for solving forward and inverse remote sensing problems, providing both accurate and fast solutions. Two examples of multi-neural network systems for the determination of cloud properties and for the retrieval of total columns of ozone using satellite data are presented. The developed algorithms based on multi-neural network are currently being used for the operational processing of European atmospheric satellite sensors and will play a key role in related satellite missions planed for the near future.

Pathogenesis, imaging and clinical characteristics of CF and non-CF bronchiectasis.

PubMed

Schäfer, Jürgen; Griese, Matthias; Chandrasekaran, Ravishankar; Chotirmall, Sanjay H; Hartl, Dominik

2018-05-22

Bronchiectasis is a common feature of severe inherited and acquired pulmonary disease conditions. Among inherited diseases, cystic fibrosis (CF) is the major disorder associated with bronchiectasis, while acquired conditions frequently featuring bronchiectasis include post-infective bronchiectasis and chronic obstructive pulmonary disease (COPD). Mechanistically, bronchiectasis is driven by a complex interplay of inflammation and infection with neutrophilic inflammation playing a predominant role. The clinical characterization and management of bronchiectasis should involve a precise diagnostic workup, tailored therapeutic strategies and pulmonary imaging that has become an essential tool for the diagnosis and follow-up of bronchiectasis. Prospective future studies are required to optimize the diagnostic and therapeutic management of bronchiectasis, particularly in heterogeneous non-CF bronchiectasis populations.

CMS tracker towards the HL-LHC

NASA Astrophysics Data System (ADS)

Alunni Solestizi, L.

2015-01-01

In sight of the incoming new LHC era (High Luminosity - LHC), characterized by a jump forward in the precision boundary and in the event rate, all the CMS sub-detector are developing and studying innovative strategies of trigger, pattern recognition, event timing and so on. A crucial aspect will be the online event selection: a totally new paradigm is needed, given the huge amount of events. In this picture the most granular and innermost sub-detector, the tracker, will play a decisive role. The phase-2 tracker will be involved in the L1 Trigger and, taking advantage of both the Associative Memories and the FPGA, it can ensure a trigger decision in proper time and with satisfactory performances.

Controlador para un Reloj GPS de Referencia en el Protocolo NTP

NASA Astrophysics Data System (ADS)

Hauscarriaga, F.; Bareilles, F. A.

The synchronization between computers in a local network plays a very important role on enviroments similar to IAR. Calculations for exact time are needed before, during and after an observation. For this purpose the IAR's GNU/Linux Software Development Team implemented a driver inside NTP protocol (an internet standard for time synchronization of computers) for a GPS receiver acquired a few years ago by IAR, which did not have support in such protocol. Today our Institute has a stable and reliable time base synchronized to atomic clocks on board GPS Satellites according to computers's synchronization standard, offering precise time services to all scientific community and particularly to the University of La Plata. FULL TEXT IN SPANISH

Androgen Receptor Signaling in Bladder Cancer

PubMed Central

Li, Peng; Chen, Jinbo; Miyamoto, Hiroshi

2017-01-01

Emerging preclinical findings have indicated that steroid hormone receptor signaling plays an important role in bladder cancer outgrowth. In particular, androgen-mediated androgen receptor signals have been shown to correlate with the promotion of tumor development and progression, which may clearly explain some sex-specific differences in bladder cancer. This review summarizes and discusses the available data, suggesting the involvement of androgens and/or the androgen receptor pathways in urothelial carcinogenesis as well as tumor growth. While the precise mechanisms of the functions of the androgen receptor in urothelial cells remain far from being fully understood, current evidence may offer chemopreventive or therapeutic options, using androgen deprivation therapy, in patients with bladder cancer. PMID:28241422

General Principles for Brain Design

NASA Astrophysics Data System (ADS)

Josephson, Brian D.

2006-06-01

The task of understanding how the brain works has met with only limited success since important design concepts are not as yet incorporated in the analysis. Relevant concepts can be uncovered by studying the powerful methodologies that have evolved in the context of computer programming, raising the question of how the concepts involved there can be realised in neural hardware. Insights can be gained in regard to such issues through the study of the role played by models and representation. These insights lead on to an appreciation of the mechanisms underlying subtle capacities such as those concerned with the use of language. A precise, essentially mathematical account of such capacities is in prospect for the future.

Re-thinking our understanding of immunity: Robustness in the tissue reconstruction system.

PubMed

Truchetet, Marie-Elise; Pradeu, Thomas

2018-04-01

Robustness, understood as the maintenance of specific functionalities of a given system against internal and external perturbations, is pervasive in today's biology. Yet precise applications of this notion to the immune system have been scarce. Here we show that the concept of robustness sheds light on tissue repair, and particularly on the crucial role the immune system plays in this process. We describe the specific mechanisms, including plasticity and redundancy, by which robustness is achieved in the tissue reconstruction system (TRS). In turn, tissue repair offers a very important test case for assessing the usefulness of the concept of robustness, and identifying different varieties of robustness. Copyright © 2018 Elsevier Ltd. All rights reserved.

Stop Stalling: Mus81 Required for Efficient Replication | Center for Cancer Research

Cancer.gov

DNA replication is precisely controlled to ensure that daughter cells receive intact, accurate genetic information. Each segment of DNA must be copied only once, and the rate of replication coordinated genome-wide. Mild replication stress slows DNA synthesis and activates a pathway involving the Mus81 endonuclease, which generates a series of DNA breaks that are rapidly repaired, allowing the cell to avoid activating the S-phase checkpoint and its potentially damaging outcomes of apoptosis or error-prone repair. Mirit Aladjem, Ph.D., of CCR’s Developmental Therapeutics Branch, and her colleagues wondered whether Mus81 also plays a role in regulating the replication rate during growth in the absence of stress.

Sensitivity and systematics of calorimetric neutrino mass experiments

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

Nucciotti, A.; Cremonesi, O.; Ferri, E.

2009-12-16

A large calorimetric neutrino mass experiment using thermal detectors is expected to play a crucial role in the challenge for directly assessing the neutrino mass. We discuss and compare here two approaches for the estimation of the experimental sensitivity of such an experiment. The first method uses an analytic formulation and allows to obtain readily a close estimate over a wide range of experimental configurations. The second method is based on a Montecarlo technique and is more precise and reliable. The Montecarlo approach is then exploited to study some sources of systematic uncertainties peculiar to calorimetric experiments. Finally, the toolsmore » are applied to investigate the optimal experimental configuration of the MARE project.« less

An extensive review of commercial product labels the good, bad and ugly.

PubMed

Mrvos, R; Dean, B S; Krenzelok, E P

1986-02-01

Cautions and warnings on consumer products play an important role in the prevention and treatment of poison exposures. Frequently those exposed will follow the directions before calling the poison center, physician or emergency room. An extensive label review of 200 commercial products was conducted to determine if medical treatment advice was correct, if the general public was able to comprehend warning statements, and if warnings were adequate. We conclude there are products available that provide precise, correct information. However, there are many that contain incorrect, misleading, and often dangerous information to an unsuspecting public. Various examples of both types are given to make the poison information specialist aware of what information is presented.

A Macro-to-Micro Interface for the Control of Cellular Organization

PubMed Central

Hui, Elliot E.; Li, Chun; Agrawal, Amit; Bhatia, Sangeeta N.

2015-01-01

The spatial organization of cellular communities plays a fundamental role in determining intercellular communication and emergent behavior. However, few tools exist to modulate tissue organization at the scale of individual cells, particularly in the case of dynamic manipulation. Micromechanical reconfigurable culture achieves dynamic control of tissue organization by culturing adherent cells on microfabricated plates that can be shifted to reorganize the arrangement of the cells. While biological studies utilizing this approach have been previously reported, this paper focuses on the engineering of the device, including the mechanism for translating manual manipulation to precise microscale position control, fault-tolerant design for manufacture, and the synthetic-to-living interface. PMID:26167106

Reactive behavior, learning, and anticipation

NASA Technical Reports Server (NTRS)

Whitehead, Steven D.; Ballard, Dana H.

1989-01-01

Reactive systems always act, thinking only long enough to 'look up' the action to execute. Traditional planning systems think a lot, and act only after generating fairly precise plans. Each represents an endpoint on a spectrum. It is argued that primitive forms of reasoning, like anticipation, play an important role in reducing the cost of learning and that the decision to act or think should be based on the uncertainty associated with the utility of executing an action in a particular situation. An architecture for an adaptable reactive system is presented and it is shown how it can be augmented with a simple anticipation mechanism that can substantially reduce the cost and time of learning.

Research progress of on-the-go soil parameter sensors based on NIRS

NASA Astrophysics Data System (ADS)

An, Xiaofei; Meng, Zhijun; Wu, Guangwei; Guo, Jianhua

2014-11-01

Both the ever-increasing prices of fertilizer and growing ecological concern over chemical run-off into sources of drinking water have brought the issues of precision agriculture and site-specific management to the forefront of present technological development within agriculture and ecology. Soil is an important and basic element in agriculture production. Acquisition of soil information plays an important role in precision agriculture. The soil parameters include soil total nitrogen, phosporus, potassium, soil organic matter, soil moisture, electrical conductivity and pH value and so on. Field rapid acquisition to all the kinds of soil physical and chemical parameters is one of the most important research directions. And soil parameter real-time monitoring is also the trend of future development in precision agriculture. While developments in precision agriculture and site-specific management procedures have made significant in-roads on these issues and many researchers have developed effective means to determine soil properties, routinely obtaining robust on-the-go measurements of soil properties which are reliable enough to drive effective fertilizer application remains a challenge. NIRS technology provides a new method to obtain soil parameter with low cost and rapid advantage. In this paper, research progresses of soil on-the-go spectral sensors at domestic and abroad was combed and analyzed. There is a need for the sensing system to perform at least six key indexes for any on-the-go soil spectral sensor to be successful. The six indexes are detection limit, specificity, robustness, accuracy, cost and easy-to-use. Both the research status and problems were discussed. Finally, combining the national conditions of china, development tendency of on-the-go soil spectral sensors was proposed. In the future, on-the-go soil spectral sensors with reliable enough, sensitive enough and continuous detection would become popular in precision agriculture.

Status of internal quality control for thyroid hormones immunoassays from 2011 to 2016 in China.

PubMed

Zhang, Shishi; Wang, Wei; Zhao, Haijian; He, Falin; Zhong, Kun; Yuan, Shuai; Wang, Zhiguo

2018-01-01

Internal quality control (IQC) plays a key role in the evaluation of precision performance in clinical laboratories. This report aims to present precision status of thyroid hormones immunoassays from 2011 to 2016 in China. Through Clinet-EQA reporting system, IQC information of Triiodothyronine and Thyroxine in the form of free and total (FT3, TT3, FT4, TT4), as well as Thyroid Stimulating Hormone (TSH) were collected from participant laboratories submitting IQC data in February, 2011-2016. For each analyte, current CVs were compared among different years and measurement systems. Percentages of laboratories meeting five allowable imprecision specifications (pass rates) were also calculated. Analysis of IQC practice was conducted to constitute a complete report. Current CVs were decreasing significantly but pass rates increasing only for FT3 during 6 years. FT3, TT3, FT4, and TT4 had the highest pass rates comparing with 1/3TEa imprecision specification but TSH had this comparing with minimum imprecision specification derived from biological variation. Constituent ratios of four mainstream measurement systems changed insignificantly. In 2016, precision performance of Abbott and Roche systems were better than Beckman and Siemens systems for all analytes except FT3 had Siemens also better than Beckman. Analysis of IQC practice demonstrated wide variation and great progress in aspects of IQC rules and control frequency. With change of IQC practice, only FT3 had precision performance improved in 6 years. However, precision status of five analytes in China was still unsatisfying. Ongoing investigation and improvement of IQC have yet to be achieved. © 2017 Wiley Periodicals, Inc.

Personalized Herbal Medicine? A Roadmap for Convergence of Herbal and Precision Medicine Biomarker Innovations.

PubMed

Thomford, Nicholas Ekow; Dzobo, Kevin; Chimusa, Emile; Andrae-Marobela, Kerstin; Chirikure, Shadreck; Wonkam, Ambroise; Dandara, Collet

2018-06-01

While drugs remain the cornerstone of medicine, herbal medicine is an important comedication worldwide. Thus, precision medicine ought to face this clinical reality and develop "companion diagnostics" for drugs as well as herbal medicines. Yet, many are in denial with respect to the extent of use of traditional/herbal medicines, overlooking that a considerable number of contemporary therapeutic drugs trace their discovery from herbal medicines. This expert review underscores that absent such appropriate attention on both classical drug therapy and herbal medicines, precision medicine biomarkers will likely not stand the full test of clinical practice while patients continue to use both drugs and herbal medicines and, yet the biomarker research and applications focus only (or mostly) on drug therapy. This asymmetry in biomarker innovation strategy needs urgent attention from a wide range of innovation actors worldwide, including governments, research funders, scientists, community leaders, civil society organizations, herbal, pharmaceutical, and insurance industries, policymakers, and social/political scientists. We discuss the various dimensions of a future convergence map between herbal and conventional medicine, and conclude with a set of concrete strategies on how best to integrate biomarker research in a realm of both herbal and drug treatment. Africa, by virtue of its vast experience and exposure in herbal medicine and a "pregnant" life sciences innovation ecosystem, could play a game-changing role for the "birth" of biomarker-informed personalized herbal medicine in the near future. At this critical juncture when precision medicine initiatives are being rolled out worldwide, precision/personalized herbal medicine is both timely and essential for modern therapeutics, not to mention biomarker innovations that stand the test of real-life practices and implementation in the clinic and society.

Comparison of Relative Bias, Precision, and Efficiency of Sampling Methods for Natural Enemies of Soybean Aphid (Hemiptera: Aphididae).

PubMed

Bannerman, J A; Costamagna, A C; McCornack, B P; Ragsdale, D W

2015-06-01

Generalist natural enemies play an important role in controlling soybean aphid, Aphis glycines (Hemiptera: Aphididae), in North America. Several sampling methods are used to monitor natural enemy populations in soybean, but there has been little work investigating their relative bias, precision, and efficiency. We compare five sampling methods: quadrats, whole-plant counts, sweep-netting, walking transects, and yellow sticky cards to determine the most practical methods for sampling the three most prominent species, which included Harmonia axyridis (Pallas), Coccinella septempunctata L. (Coleoptera: Coccinellidae), and Orius insidiosus (Say) (Hemiptera: Anthocoridae). We show an important time by sampling method interaction indicated by diverging community similarities within and between sampling methods as the growing season progressed. Similarly, correlations between sampling methods for the three most abundant species over multiple time periods indicated differences in relative bias between sampling methods and suggests that bias is not consistent throughout the growing season, particularly for sticky cards and whole-plant samples. Furthermore, we show that sticky cards produce strongly biased capture rates relative to the other four sampling methods. Precision and efficiency differed between sampling methods and sticky cards produced the most precise (but highly biased) results for adult natural enemies, while walking transects and whole-plant counts were the most efficient methods for detecting coccinellids and O. insidiosus, respectively. Based on bias, precision, and efficiency considerations, the most practical sampling methods for monitoring in soybean include walking transects for coccinellid detection and whole-plant counts for detection of small predators like O. insidiosus. Sweep-netting and quadrat samples are also useful for some applications, when efficiency is not paramount. © The Authors 2015. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Measuring Relativistic effects in the field of the Earth with Laser Ranged Satellites and the LARASE research program

NASA Astrophysics Data System (ADS)

Lucchesi, David; Anselmo, Luciano; Bassan, Massimo; Magnafico, Carmelo; Pardini, Carmen; Peron, Roberto; Pucacco, Giuseppe; Stanga, Ruggero; Visco, Massimo

2017-04-01

The main goal of the LARASE (LAser RAnged Satellites Experiment) research program is to obtain refined tests of Einstein's theory of General Relativity (GR) by means of very precise measurements of the round-trip time among a number of ground stations of the International Laser Ranging Service (ILRS) network and a set of geodetic satellites. These measurements are guaranteed by means of the powerful and precise Satellite Laser Ranging (SLR) technique. In particular, a big effort of LARASE is dedicated to improve the dynamical models of the LAGEOS, LAGEOS II and LARES satellites, with the objective to obtain a more precise and accurate determination of their orbit. These activities contribute to reach a final error budget that should be robust and reliable in the evaluation of the main systematic errors sources that come to play a major role in masking the relativistic precession on the orbit of these laser-ranged satellites. These error sources may be of gravitational and non-gravitational origin. It is important to stress that a more accurate and precise orbit determination, based on more reliable dynamical models, represents a fundamental prerequisite in order to reach a sub-mm precision in the root-mean-square of the SLR range residuals and, consequently, to gather benefits in the fields of geophysics and space geodesy, such as stations coordinates knowledge, geocenter determination and the realization of the Earth's reference frame. The results reached over the last year will be presented in terms of the improvements achieved in the dynamical model, in the orbit determination and, finally, in the measurement of the relativistic precessions that act on the orbit of the satellites considered.

Pivotal roles of Kupffer cells in the progression and regression of DDC-induced chronic cholangiopathy.

PubMed

Jemail, Leila; Miyao, Masashi; Kotani, Hirokazu; Kawai, Chihiro; Minami, Hirozo; Abiru, Hitoshi; Tamaki, Keiji

2018-04-23

Kupffer cells (KCs) are key players in maintaining tissue homeostasis and are involved in various liver diseases. However, the roles of KCs in the pathogenesis of cholangiopathy are largely unknown. We aimed to investigate the precise roles of KCs in both the progression and regression phases of the 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-induced cholangiopathy model. In the early phase of DDC-induced cholangiopathy, the number of KCs significantly increased over time. Moreover, KCs were associated with abnormal phenotypic changes in other liver cells, such as hepatocytes, biliary epithelial cells, liver sinusoidal endothelial cells, and hepatic stellate cells. In contrast, KC depletion by clodronate administration suppressed the progression of the disease, and maintained the phenotypes of other cells. In the regression phase, the numbers of KCs significantly decreased, and the cells redifferentiated to their quiescent state. In contrast, KC depletion delayed the recovery of cells by maintaining other liver cells in an active state. These findings suggest that KCs play detrimental roles in the progression phase; however, they are beneficial in the regression phase by mediating interactions between other liver cells. Our data provide new insights into the roles of KCs in the pathogenesis of cholangiopathy.

Dynamic balance of excitation and inhibition rapidly modulates spike probability and precision in feed-forward hippocampal circuits

PubMed Central

Wahlstrom-Helgren, Sarah

2016-01-01

Feed-forward inhibitory (FFI) circuits are important for many information-processing functions. FFI circuit operations critically depend on the balance and timing between the excitatory and inhibitory components, which undergo rapid dynamic changes during neural activity due to short-term plasticity (STP) of both components. How dynamic changes in excitation/inhibition (E/I) balance during spike trains influence FFI circuit operations remains poorly understood. In the current study we examined the role of STP in the FFI circuit functions in the mouse hippocampus. Using a coincidence detection paradigm with simultaneous activation of two Schaffer collateral inputs, we found that the spiking probability in the target CA1 neuron was increased while spike precision concomitantly decreased during high-frequency bursts compared with a single spike. Blocking inhibitory synaptic transmission revealed that dynamics of inhibition predominately modulates the spike precision but not the changes in spiking probability, whereas the latter is modulated by the dynamics of excitation. Further analyses combining whole cell recordings and simulations of the FFI circuit suggested that dynamics of the inhibitory circuit component may influence spiking behavior during bursts by broadening the width of excitatory postsynaptic responses and that the strength of this modulation depends on the basal E/I ratio. We verified these predictions using a mouse model of fragile X syndrome, which has an elevated E/I ratio, and found a strongly reduced modulation of postsynaptic response width during bursts. Our results suggest that changes in the dynamics of excitatory and inhibitory circuit components due to STP play important yet distinct roles in modulating the properties of FFI circuits. PMID:27605532

Precision agriculture: Data to knowledge decision

USDA-ARS?s Scientific Manuscript database

From the development of the first viable variable-rate fertilizer systems in the upper Midwest USA, precision agriculture is now about two decades old. In that time, new technologies have come into play, but the overall goal of using spatial data to create actionable knowledge that can then be used ...

Posterior parietal cortex mediates encoding and maintenance processes in change blindness.

PubMed

Tseng, Philip; Hsu, Tzu-Yu; Muggleton, Neil G; Tzeng, Ovid J L; Hung, Daisy L; Juan, Chi-Hung

2010-03-01

It is commonly accepted that right posterior parietal cortex (PPC) plays an important role in updating spatial representations, directing visuospatial attention, and planning actions. However, recent studies suggest that right PPC may also be involved in processes that are more closely associated with our visual awareness as its activation level positively correlates with successful conscious change detection (Beck, D.M., Rees, G., Frith, C.D., & Lavie, N. (2001). Neural correlates of change detection and change blindness. Nature Neuroscience, 4, 645-650.). Furthermore, disruption of its activity increases the occurrences of change blindness, thus suggesting a causal role for right PPC in change detection (Beck, D.M., Muggleton, N., Walsh, V., & Lavie, N. (2006). Right parietal cortex plays a critical role in change blindness. Cerebral Cortex, 16, 712-717.). In the context of a 1-shot change detection paradigm, we applied transcranial magnetic stimulation (TMS) during different time intervals to elucidate the temporally precise involvement of PPC in change detection. While subjects attempted to detect changes between two image sets separated by a brief time interval, TMS was applied either during the presentation of picture 1 when subjects were encoding and maintaining information into visual short-term memory, or picture 2 when subjects were retrieving information relating to picture 1 and comparing it to picture 2. Our results show that change blindness occurred more often when TMS was applied during the viewing of picture 1, which implies that right PPC plays a crucial role in the processes of encoding and maintaining information in visual short-term memory. In addition, since our stimuli did not involve changes in spatial locations, our findings also support previous studies suggesting that PPC may be involved in the processes of encoding non-spatial visual information (Todd, J.J. & Marois, R. (2004). Capacity limit of visual short-term memory in human posterior parietal cortex. Nature, 428, 751-754.). Copyright (c) 2009 Elsevier Ltd. All rights reserved.

The student with a thousand faces: from the ethics in video games to becoming a citizen

NASA Astrophysics Data System (ADS)

Muñoz, Yupanqui J.; El-Hani, Charbel N.

2012-12-01

Video games, as technological and cultural artifacts of considerable influence in the contemporary society, play an important role in the construction of identities, just as other artifacts (e.g., books, newspapers, television) played for a long time. In this paper, we discuss this role by considering video games under two concepts, othering and technopoly, and focus on how these concepts demand that we deepen our understanding of the ethics of video games. We address here how the construction of identities within video games involves othering process, that is, processes through which, when signifying and identifying `Ourselves', we create and marginalize `Others'. Moreover, we discuss how video games can play an important role in the legitimation of the technopoly, understood as a totalitarian regime related to science, technology and their place in our societies. Under these two concepts, understanding the ethics of video games goes beyond the controversy about their violence. The main focus of discussion should lie in how the ethics of video games is related to their part in the formation of the players' citizenship. Examining several examples of electronic games, we consider how video games provide a rich experience in which the player has the opportunity to develop a practical wisdom ( phronesis), which can lead her to be a virtuous being. However, they can be also harmful to the moral experiences of the subjects when they show unethical contents related to othering processes that are not so clearly and openly condemned as violence, as in the cases of sexism, racism or xenophobia. Rather than leading us to conclude that video games needed to be banned or censored, this argument makes us highlight their role in the (science) education of critical, socially responsible, ethical, and politically active citizens, precisely because they encompass othering processes and science, technology, and society relationships.

Shedding the Ego: Drama-Based Role-Play and Identity in Distance Language Tuition

ERIC Educational Resources Information Center

Brash, Barbel; Warnecke, Sylvia

2009-01-01

In this article, the authors attempt to answer the following questions: How do we understand role-play? How are role-play and identity linked? What are the purposes, benefits and challenges of role-play as a teaching tool? What are the roles of students and teachers in role-play? What does role-play add to telephone tutorials and online…

High-Precision 40Ar/39Ar dating of the Deccan Traps

NASA Astrophysics Data System (ADS)

Sprain, C. J.; Renne, P. R.; Richards, M. A.; Self, S.; Vanderkluysen, L.; Pande, K.; Morgan, L. E.; Cosca, M. A.

2015-12-01

The Deccan Traps (DT) have been strongly implicated over the past thirty years as a potential cause of the mass extinctions at the Cretaceous-Paleogene boundary (KPB). While a broad coincidence between the DT eruptions and the KPB is increasingly clear, variables such as tempo, volume of eruptions, and amount of associated climate-modifying volatiles, are too poorly constrained to properly assess causality. In order to appropriately test whether the DT played a role in the mass extinctions a high-precision geochronologic framework defining the timing and tempo of volcanic eruptions is needed. Recent high-precision U/Pb dating of zircons from inferred paleosols (red boles) and melt segregation horizons is the only available geochronology of the DT that is sufficiently precise to resolve age differences of less than 100 ka (Schoene et al., 2015). While this technique can achieve high-precision dates for individual zircon crystals, protracted age distributions may not include the actual eruption age. Moreover, the applicability of U/Pb dating in the DT is limited as suitable material is only sporadically present and therefore the technique is unlikely to achieve the resolution necessary to assess the tempo of DT eruptions. To mediate these limitations, we present new high-precision 40Ar/39Ar ages for plagioclase separated from the lava flows sampled from each of ten chemostratigraphically-defined formations within the Western Ghats. Multiple (N = 1-4) plateau ages from each sample and detailed neutron fluence monitoring during irradiation yield ages with precision commonly better than 100 ka (1 sigma). Results provide the first precise location of the KPB within the DT eruption sequence, which approximately coincides with major changes in eruption frequency, flow-field volumes, extent of crustal contamination, and degree of fractionation. Collectively, these results suggest that a state shift occurred in the DT magma system within ~50 ka of the Chicxulub impact, consistent with transient effects of seismic energy associated with the impact. Further, our new data invalidate the concept of three discrete eruption pulses in the Western Ghats (Chenet et al., 2007, 2009; Keller et al., 2008) and rather indicate only a sharp increase in mean volumetric eruption rates near the KPB.

Eos Negatively Regulates Human γ-globin Gene Transcription during Erythroid Differentiation

PubMed Central

Yu, Hai-Chuan; Zhao, Hua-Lu; Wu, Zhi-Kui; Zhang, Jun-Wu

2011-01-01

Background Human globin gene expression is precisely regulated by a complicated network of transcription factors and chromatin modifying activities during development and erythropoiesis. Eos (Ikaros family zinc finger 4, IKZF4), a member of the zinc finger transcription factor Ikaros family, plays a pivotal role as a repressor of gene expression. The aim of this study was to examine the role of Eos in globin gene regulation. Methodology/Principal Findings Western blot and quantitative real-time PCR detected a gradual decrease in Eos expression during erythroid differentiation of hemin-induced K562 cells and Epo-induced CD34+ hematopoietic stem/progenitor cells (HPCs). DNA transfection and lentivirus-mediated gene transfer demonstrated that the enforced expression of Eos significantly represses the expression of γ-globin, but not other globin genes, in K562 cells and CD34+ HPCs. Consistent with a direct role of Eos in globin gene regulation, chromatin immunoprecipitaion and dual-luciferase reporter assays identified three discrete sites located in the DNase I hypersensitivity site 3 (HS3) of the β-globin locus control region (LCR), the promoter regions of the Gγ- and Aγ- globin genes, as functional binding sites of Eos protein. A chromosome conformation capture (3C) assay indicated that Eos may repress the interaction between the LCR and the γ-globin gene promoter. In addition, erythroid differentiation was inhibited by enforced expression of Eos in K562 cells and CD34+ HPCs. Conclusions/Significance Our results demonstrate that Eos plays an important role in the transcriptional regulation of the γ-globin gene during erythroid differentiation. PMID:21829552

Sclerostin's role in bone's adaptive response to mechanical loading.

PubMed

Galea, Gabriel L; Lanyon, Lance E; Price, Joanna S

2017-03-01

Mechanical loading is the primary functional determinant of bone mass and architecture, and osteocytes play a key role in translating mechanical signals into (re)modelling responses. Although the precise mechanisms remain unclear, Wnt signalling pathway components, and the anti-osteogenic canonical Wnt inhibitor Sost/sclerostin in particular, play an important role in regulating bone's adaptive response to loading. Increases in loading-engendered strains down-regulate osteocyte sclerostin expression, whereas reduced strains, as in disuse, are associated with increased sclerostin production and bone loss. However, while sclerostin up-regulation appears to be necessary for the loss of bone with disuse, the role of sclerostin in the osteogenic response to loading is more complex. While mice unable to down-regulate sclerostin do not gain bone with loading, Sost knockout mice have an enhanced osteogenic response to loading. The molecular mechanisms by which osteocytes sense and transduce loading-related stimuli into changes in sclerostin expression remain unclear but include several, potentially interlinked, signalling cascades involving periostin/integrin, prostaglandin, estrogen receptor, calcium/NO and Igf signalling. Deciphering the mechanisms by which changes in the mechanical environment regulate sclerostin production may lead to the development of therapeutic strategies that can reverse the skeletal structural deterioration characteristic of disuse and age-related osteoporosis and enhance bones' functional adaptation to loading. By enhancing the osteogenic potential of the context in which individual therapies such as sclerostin antibodies act it may become possible to both prevent and reverse the age-related skeletal structural deterioration characteristic of osteoporosis. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Impact of Labile Zinc on Heart Function: From Physiology to Pathophysiology

PubMed Central

Turan, Belma; Tuncay, Erkan

2017-01-01

Zinc plays an important role in biological systems as bound and histochemically reactive labile Zn2+. Although Zn2+ concentration is in the nM range in cardiomyocytes at rest and increases dramatically under stimulation, very little is known about precise mechanisms controlling the intracellular distribution of Zn2+ and its variations during cardiac function. Recent studies are focused on molecular and cellular aspects of labile Zn2+ and its homeostasis in mammalian cells and growing evidence clarified the molecular mechanisms underlying Zn2+-diverse functions in the heart, leading to the discovery of novel physiological functions of labile Zn2+ in parallel to the discovery of subcellular localization of Zn2+-transporters in cardiomyocytes. Additionally, important experimental data suggest a central role of intracellular labile Zn2+ in excitation-contraction coupling in cardiomyocytes by shaping Ca2+ dynamics. Cellular labile Zn2+ is tightly regulated against its adverse effects through either Zn2+-transporters, Zn2+-binding molecules or Zn2+-sensors, and, therefore plays a critical role in cellular signaling pathways. The present review summarizes the current understanding of the physiological role of cellular labile Zn2+ distribution in cardiomyocytes and how a remodeling of cellular Zn2+-homeostasis can be important in proper cell function with Zn2+-transporters under hyperglycemia. We also emphasize the recent investigations on Zn2+-transporter functions from the standpoint of human heart health to diseases together with their clinical interest as target proteins in the heart under pathological condition, such as diabetes. PMID:29137144

Psychiatrists' Perceptions of Role-Playing Games.

PubMed

Lis, Eric; Chiniara, Carl; Biskin, Robert; Montoro, Richard

2015-09-01

The literature has seen a surge in research on the mental health impacts of technologies such as Facebook, video games, and massively-multiplayer online role-playing games such as World of Warcraft, but little is known regarding the mental health impact of non-video role-playing games, such as Dungeons & Dragons. The present study examines how psychiatrists' perceive role-playing games and whether they play them. Psychiatrists at a tertiary care centre in Canada completed a questionnaire assessing history of playing role-playing games and whether they associate them with psychopathology. Forty-eight psychiatrists responded. Twenty-three percent have played a role-playing game over their lifetimes. Twenty-two percent believed there was an association between psychopathology and role-playing games. A majority of psychiatrists who responded do not associate role-playing games with psychopathology. Implications for clinical practice and future research are discussed.

Medical robotics.

PubMed

Ferrigno, Giancarlo; Baroni, Guido; Casolo, Federico; De Momi, Elena; Gini, Giuseppina; Matteucci, Matteo; Pedrocchi, Alessandra

2011-01-01

Information and communication technology (ICT) and mechatronics play a basic role in medical robotics and computer-aided therapy. In the last three decades, in fact, ICT technology has strongly entered the health-care field, bringing in new techniques to support therapy and rehabilitation. In this frame, medical robotics is an expansion of the service and professional robotics as well as other technologies, as surgical navigation has been introduced especially in minimally invasive surgery. Localization systems also provide treatments in radiotherapy and radiosurgery with high precision. Virtual or augmented reality plays a role for both surgical training and planning and for safe rehabilitation in the first stage of the recovery from neurological diseases. Also, in the chronic phase of motor diseases, robotics helps with special assistive devices and prostheses. Although, in the past, the actual need and advantage of navigation, localization, and robotics in surgery and therapy has been in doubt, today, the availability of better hardware (e.g., microrobots) and more sophisticated algorithms(e.g., machine learning and other cognitive approaches)has largely increased the field of applications of these technologies,making it more likely that, in the near future, their presence will be dramatically increased, taking advantage of the generational change of the end users and the increasing request of quality in health-care delivery and management.

Dynamic Control of Synaptic Adhesion and Organizing Molecules in Synaptic Plasticity

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

Rudenko, Gabby

Synapses play a critical role in establishing and maintaining neural circuits, permitting targeted information transfer throughout the brain. A large portfolio of synaptic adhesion/organizing molecules (SAMs) exists in the mammalian brain involved in synapse development and maintenance. SAMs bind protein partners, formingtrans-complexes spanning the synaptic cleft orcis-complexes attached to the same synaptic membrane. SAMs play key roles in cell adhesion and in organizing protein interaction networks; they can also provide mechanisms of recognition, generate scaffolds onto which partners can dock, and likely take part in signaling processes as well. SAMs are regulated through a portfolio of different mechanisms that affectmore » their protein levels, precise localization, stability, and the availability of their partners at synapses. Interaction of SAMs with their partners can further be strengthened or weakened through alternative splicing, competing protein partners, ectodomain shedding, or astrocytically secreted factors. Given that numerous SAMs appear altered by synaptic activity, in vivo, these molecules may be used to dynamically scale up or scale down synaptic communication. Many SAMs, including neurexins, neuroligins, cadherins, and contactins, are now implicated in neuropsychiatric and neurodevelopmental diseases, such as autism spectrum disorder, schizophrenia, and bipolar disorder and studying their molecular mechanisms holds promise for developing novel therapeutics.« less

Temperature impacts on deep-sea biodiversity.

PubMed

Yasuhara, Moriaki; Danovaro, Roberto

2016-05-01

Temperature is considered to be a fundamental factor controlling biodiversity in marine ecosystems, but precisely what role temperature plays in modulating diversity is still not clear. The deep ocean, lacking light and in situ photosynthetic primary production, is an ideal model system to test the effects of temperature changes on biodiversity. Here we synthesize current knowledge on temperature-diversity relationships in the deep sea. Our results from both present and past deep-sea assemblages suggest that, when a wide range of deep-sea bottom-water temperatures is considered, a unimodal relationship exists between temperature and diversity (that may be right skewed). It is possible that temperature is important only when at relatively high and low levels but does not play a major role in the intermediate temperature range. Possible mechanisms explaining the temperature-biodiversity relationship include the physiological-tolerance hypothesis, the metabolic hypothesis, island biogeography theory, or some combination of these. The possible unimodal relationship discussed here may allow us to identify tipping points at which on-going global change and deep-water warming may increase or decrease deep-sea biodiversity. Predicted changes in deep-sea temperatures due to human-induced climate change may have more adverse consequences than expected considering the sensitivity of deep-sea ecosystems to temperature changes. © 2014 Cambridge Philosophical Society.

Image registration: enabling technology for image guided surgery and therapy.

PubMed

Sauer, Frank

2005-01-01

Imaging looks inside the patient's body, exposing the patient's anatomy beyond what is visible on the surface. Medical imaging has a very successful history for medical diagnosis. It also plays an increasingly important role as enabling technology for minimally invasive procedures. Interventional procedures (e.g. catheter based cardiac interventions) are traditionally supported by intra-procedure imaging (X-ray fluoro, ultrasound). There is realtime feedback, but the images provide limited information. Surgical procedures are traditionally supported with pre-operative images (CT, MR). The image quality can be very good; however, the link between images and patient has been lost. For both cases, image registration can play an essential role -augmenting intra-op images with pre-op images, and mapping pre-op images to the patient's body. We will present examples of both approaches from an application oriented perspective, covering electrophysiology, radiation therapy, and neuro-surgery. Ultimately, as the boundaries between interventional radiology and surgery are becoming blurry, also the different methods for image guidance will merge. Image guidance will draw upon a combination of pre-op and intra-op imaging together with magnetic or optical tracking systems, and enable precise minimally invasive procedures. The information is registered into a common coordinate system, and allows advanced methods for visualization such as augmented reality or advanced methods for therapy delivery such as robotics.

Akt1 deficiency diminishes skeletal muscle hypertrophy by reducing satellite cell proliferation.

PubMed

Moriya, Nobuki; Miyazaki, Mitsunori

2018-05-01

Skeletal muscle mass is determined by the net dynamic balance between protein synthesis and degradation. Although the Akt/mechanistic target of rapamycin (mTOR)-dependent pathway plays an important role in promoting protein synthesis and subsequent skeletal muscle hypertrophy, the precise molecular regulation of mTOR activity by the upstream protein kinase Akt is largely unknown. In addition, the activation of satellite cells has been indicated as a key regulator of muscle mass. However, the requirement of satellite cells for load-induced skeletal muscle hypertrophy is still under intense debate. In this study, female germline Akt1 knockout (KO) mice were used to examine whether Akt1 deficiency attenuates load-induced skeletal muscle hypertrophy through suppressing mTOR-dependent signaling and satellite cell proliferation. Akt1 KO mice showed a blunted hypertrophic response of skeletal muscle, with a diminished rate of satellite cell proliferation following mechanical overload. In contrast, Akt1 deficiency did not affect the load-induced activation of mTOR signaling and the subsequent enhanced rate of protein synthesis in skeletal muscle. These observations suggest that the load-induced activation of mTOR signaling occurs independently of Akt1 regulation and that Akt1 plays a critical role in regulating satellite cell proliferation during load-induced muscle hypertrophy.

Percutaneous treatment of intervertebral disc herniation.

PubMed

Buy, Xavier; Gangi, Afshin

2010-06-01

Interventional radiology plays a major role in the management of symptomatic intervertebral disc herniations. In the absence of significant pain relief with conservative treatment including oral pain killers and anti-inflammatory drugs, selective image-guided periradicular infiltrations are generally indicated. The precise control of needle positioning allows optimal distribution of steroids along the painful nerve root. After 6 weeks of failure of conservative treatment including periradicular infiltration, treatment aiming to decompress or remove the herniation is considered. Conventional open surgery offers suboptimal results and is associated with significant morbidity. To achieve minimally invasive discal decompression, different percutaneous techniques have been developed. Their principle is to remove a small volume of nucleus, which results in an important reduction of intradiscal pressure and subsequently reduction of pressure inside the disc herniation. However, only contained disc herniations determined by computed tomography or magnetic resonance are indicated for these techniques. Thermal techniques such as radiofrequency or laser nucleotomy seem to be more effective than purely mechanical nucleotomy; indeed, they achieve discal decompression but also thermal destruction of intradiscal nociceptors, which may play a major role in the physiopathology of discal pain. The techniques of image-guided spinal periradicular infiltration and percutaneous nucleotomy with laser and radiofrequency are presented with emphasis on their best indications.

Hydraulics play an important role in causing low growth rate and dieback of aging Pinus sylvestris var. mongolica trees in plantations of Northeast China.

PubMed

Liu, Yan-Yan; Wang, Ai-Ying; An, Yu-Ning; Lian, Pei-Yong; Wu, De-Dong; Zhu, Jiao-Jun; Meinzer, Frederick C; Hao, Guang-You

2018-07-01

The frequently observed forest decline in water-limited regions may be associated with impaired tree hydraulics, but the precise physiological mechanisms remain poorly understood. We compared hydraulic architecture of Mongolian pine (Pinus sylvestris var. mongolica) trees of different size classes from a plantation and a natural forest site to test whether greater hydraulic limitation with increasing size plays an important role in tree decline observed in the more water-limited plantation site. We found that trees from plantations overall showed significantly lower stem hydraulic efficiency. More importantly, plantation-grown trees showed significant declines in stem hydraulic conductivity and hydraulic safety margins as well as syndromes of stronger drought stress with increasing size, whereas no such trends were observed at the natural forest site. Most notably, the leaf to sapwood area ratio (LA/SA) showed a strong linear decline with increasing tree size at the plantation site. Although compensatory adjustments in LA/SA may mitigate the effect of increased water stress in larger trees, they may result in greater risk of carbon imbalance, eventually limiting tree growth at the plantation site. Our results provide a potential mechanistic explanation for the widespread decline of Mongolian pine trees in plantations of Northern China. © 2018 John Wiley & Sons Ltd.

Dynamic Control of Synaptic Adhesion and Organizing Molecules in Synaptic Plasticity

PubMed Central

2017-01-01

Synapses play a critical role in establishing and maintaining neural circuits, permitting targeted information transfer throughout the brain. A large portfolio of synaptic adhesion/organizing molecules (SAMs) exists in the mammalian brain involved in synapse development and maintenance. SAMs bind protein partners, forming trans-complexes spanning the synaptic cleft or cis-complexes attached to the same synaptic membrane. SAMs play key roles in cell adhesion and in organizing protein interaction networks; they can also provide mechanisms of recognition, generate scaffolds onto which partners can dock, and likely take part in signaling processes as well. SAMs are regulated through a portfolio of different mechanisms that affect their protein levels, precise localization, stability, and the availability of their partners at synapses. Interaction of SAMs with their partners can further be strengthened or weakened through alternative splicing, competing protein partners, ectodomain shedding, or astrocytically secreted factors. Given that numerous SAMs appear altered by synaptic activity, in vivo, these molecules may be used to dynamically scale up or scale down synaptic communication. Many SAMs, including neurexins, neuroligins, cadherins, and contactins, are now implicated in neuropsychiatric and neurodevelopmental diseases, such as autism spectrum disorder, schizophrenia, and bipolar disorder and studying their molecular mechanisms holds promise for developing novel therapeutics. PMID:28255461

The juxtamembrane regions of human receptor tyrosine kinases exhibit conserved interaction sites with anionic lipids

PubMed Central

Hedger, George; Sansom, Mark S. P.; Koldsø, Heidi

2015-01-01

Receptor tyrosine kinases (RTKs) play a critical role in diverse cellular processes and their activity is regulated by lipids in the surrounding membrane, including PIP2 (phosphatidylinositol-4,5-bisphosphate) in the inner leaflet, and GM3 (monosialodihexosylganglioside) in the outer leaflet. However, the precise details of the interactions at the molecular level remain to be fully characterised. Using a multiscale molecular dynamics simulation approach, we comprehensively characterise anionic lipid interactions with all 58 known human RTKs. Our results demonstrate that the juxtamembrane (JM) regions of RTKs are critical for inducing clustering of anionic lipids, including PIP2, both in simple asymmetric bilayers, and in more complex mixed membranes. Clustering is predominantly driven by interactions between a conserved cluster of basic residues within the first five positions of the JM region, and negatively charged lipid headgroups. This highlights a conserved interaction pattern shared across the human RTK family. In particular predominantly the N-terminal residues of the JM region are involved in the interactions with PIP2, whilst residues within the distal JM region exhibit comparatively less lipid specificity. Our results suggest that JM–lipid interactions play a key role in RTK structure and function, and more generally in the nanoscale organisation of receptor-containing cell membranes. PMID:25779975

Overview and forensic investigation approaches of the gaming console Sony PlayStation Portable

NASA Astrophysics Data System (ADS)

Schön, Stephan; Schön, Ralph; Kröger, Knut; Creutzburg, Reiner

2013-03-01

This paper addresses the forensically interesting features of the Sony PlayStation Portable game console. The construction and the internal structure are analyzed precisely and interesting forensic features of the operating system and the file system are presented.

Far-field interference of a neutron white beam and the applications to noninvasive phase-contrast imaging

NASA Astrophysics Data System (ADS)

Pushin, D. A.; Sarenac, D.; Hussey, D. S.; Miao, H.; Arif, M.; Cory, D. G.; Huber, M. G.; Jacobson, D. L.; LaManna, J. M.; Parker, J. D.; Shinohara, T.; Ueno, W.; Wen, H.

2017-04-01

The phenomenon of interference plays a crucial role in the field of precision measurement science. Wave-particle duality has expanded the well-known interference effects of electromagnetic waves to massive particles. The majority of the wave-particle interference experiments require a near monochromatic beam which limits its applications due to the resulting low intensity. Here we demonstrate white beam interference in the far-field regime using a two-phase-grating neutron interferometer and its application to phase-contrast imaging. The functionality of this interferometer is based on the universal moiré effect that allows us to improve upon the standard Lau setup. Interference fringes were observed with monochromatic and polychromatic neutron beams for both continuous and pulsed beams. Far-field neutron interferometry allows for the full utilization of intense neutron sources for precision measurements of gradient fields. It also overcomes the alignment, stability, and fabrication challenges associated with the more familiar perfect-crystal neutron interferometer, as well as avoids the loss of intensity due to the absorption analyzer grating requirement in Talbot-Lau interferometer.

Networks and games for precision medicine.

PubMed

Biane, Célia; Delaplace, Franck; Klaudel, Hanna

2016-12-01

Recent advances in omics technologies provide the leverage for the emergence of precision medicine that aims at personalizing therapy to patient. In this undertaking, computational methods play a central role for assisting physicians in their clinical decision-making by combining data analysis and systems biology modelling. Complex diseases such as cancer or diabetes arise from the intricate interplay of various biological molecules. Therefore, assessing drug efficiency requires to study the effects of elementary perturbations caused by diseases on relevant biological networks. In this paper, we propose a computational framework called Network-Action Game applied to best drug selection problem combining Game Theory and discrete models of dynamics (Boolean networks). Decision-making is modelled using Game Theory that defines the process of drug selection among alternative possibilities, while Boolean networks are used to model the effects of the interplay between disease and drugs actions on the patient's molecular system. The actions/strategies of disease and drugs are focused on arc alterations of the interactome. The efficiency of this framework has been evaluated for drug prediction on a model of breast cancer signalling. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Inactivation of Pol θ and C-NHEJ eliminates off-target integration of exogenous DNA.

PubMed

Zelensky, Alex N; Schimmel, Joost; Kool, Hanneke; Kanaar, Roland; Tijsterman, Marcel

2017-07-07

Off-target or random integration of exogenous DNA hampers precise genomic engineering and presents a safety risk in clinical gene therapy strategies. Genetic definition of random integration has been lacking for decades. Here, we show that the A-family DNA polymerase θ (Pol θ) promotes random integration, while canonical non-homologous DNA end joining plays a secondary role; cells double deficient for polymerase θ and canonical non-homologous DNA end joining are devoid of any integration events, demonstrating that these two mechanisms define random integration. In contrast, homologous recombination is not reduced in these cells and gene targeting is improved to 100% efficiency. Such complete reversal of integration outcome, from predominately random integration to exclusively gene targeting, provides a rational way forward to improve the efficacy and safety of DNA delivery and gene correction approaches.Random off-target integration events can impair precise gene targeting and poses a safety risk for gene therapy. Here the authors show that repression of polymerase θ and classical non-homologous recombination eliminates random integration.

A spectro-interferometric view of l Carinae's modulated pulsations

NASA Astrophysics Data System (ADS)

Anderson, Richard I.; Mérand, Antoine; Kervella, Pierre; Breitfelder, Joanne; Eyer, Laurent; Gallenne, Alexandre

Classical Cepheids are radially pulsating stars that enable important tests of stellar evolution and play a crucial role in the calibration of the local Hubble constant. l Carinae is a particularly well-known distance calibrator, being the closest long-period (P ~ 35.5 d) Cepheid and subtending the largest angular diameter. We have carried out an unprecedented observing program to investigate whether recently discovered cycle-to-cycle changes (modulations) of l Carinae's radial velocity (RV) variability are mirrored by its variability in angular size. To this end, we have secured a fully contemporaneous dataset of high-precision RVs and high-precision angular diameters. Here we provide a concise summary of our project and report preliminary results. We confirm the modulated nature of the RV variability and find tentative evidence of cycle-to-cycle differences in l Car's maximal angular diameter. Our analysis is exploring the limits of state-of-the-art instrumentation and reveals additional complexity in the pulsations of Cepheids. If confirmed, our result suggests a previously unknown pulsation cycle dependence of projection factors required for determining Cepheid distances via the Baade-Wesselink technique.

Link between cognitive neuroscience and education: the case of clinical assessment of developmental dyscalculia.

PubMed

Rubinsten, Orly

2015-01-01

In recent years, cognitive neuroscience research has identified several biological and cognitive features of number processing deficits that may now make it possible to diagnose mental or educational impairments in arithmetic, even earlier and more precisely than is possible using traditional assessment tools. We provide two sets of recommendations for improving cognitive assessment tools, using the important case of mathematics as an example. (1) neurocognitive tests would benefit substantially from incorporating assessments (based on findings from cognitive neuroscience) that entail systematic manipulation of fundamental aspects of number processing. Tests that focus on evaluating networks of core neurocognitive deficits have considerable potential to lead to more precise diagnosis and to provide the basis for designing specific intervention programs tailored to the deficits exhibited by the individual child. (2) implicit knowledge, derived from inspection of variables that are irrelevant to the task at hand, can also provide a useful assessment tool. Implicit knowledge is powerful and plays an important role in human development, especially in cases of psychiatric or neurological deficiencies (such as math learning disabilities or math anxiety).

Monitoring groundwater variation by satellite and implications for in-situ gravity measurements.

PubMed

Fukuda, Yoichi; Yamamoto, Keiko; Hasegawa, Takashi; Nakaegawa, Toshiyuki; Nishijima, Jun; Taniguchi, Makoto

2009-04-15

In order to establish a new technique for monitoring groundwater variations in urban areas, the applicability of precise in-situ gravity measurements and extremely high precision satellite gravity data via GRACE (Gravity Recovery and Climate Experiment) was tested. Using the GRACE data, regional scale water mass variations in four major river basins of the Indochina Peninsula were estimated. The estimated variations were compared with Soil-Vegetation-Atmosphere Transfer Scheme (SVATS) models with a river flow model of 1) globally uniform river velocity, 2) river velocity tuned by each river basin, 3) globally uniform river velocity considering groundwater storage, and 4) river velocity tuned by each river basin considering groundwater storage. Model 3) attained the best fit to the GRACE data, and the model 4) yielded almost the same values. This implies that the groundwater plays an important role in estimating the variation of total terrestrial storage. It also indicates that tuning river velocity, which is based on the in-situ measurements, needs further investigations in combination with the GRACE data. The relationships among GRACE data, SVATS models, and in-situ measurements were also discussed briefly.

Experimental Study on the Effects of Alumina Abrasive Particle Behavior in MR Polishing for MEMS Applications

PubMed Central

Kim, Dong-Woo; Cho, Myeong-Woo; Seo, Tae-Il; Shin, Young-Jae

2008-01-01

Recently, the magnetorheological (MR) polishing process has been examined as a new ultra-precision polishing technology for micro parts in MEMS applications. In the MR polishing process, the magnetic force plays a dominant role. This method uses MR fluids which contains micro abrasives as a polishing media. The objective of the present research is to shed light onto the material removal mechanism under various slurry conditions for polishing and to investigate surface characteristics, including shape analysis and surface roughness measurement, of spots obtained from the MR polishing process using alumina abrasives. A series of basic experiments were first performed to determine the optimum polishing conditions for BK7 glass using prepared slurries by changing the process parameters, such as wheel rotating speed and electric current. Using the obtained results, groove polishing was then performed and the results are investigated. Outstanding surface roughness of Ra=3.8nm was obtained on the BK7 glass specimen. The present results highlight the possibility of applying this polishing method to ultra-precision micro parts production, especially in MEMS applications. PMID:27879705

Understanding and Remediating Social-Cognitive Dysfunctions in Patients with Serious Mental Illness Using Relational Frame Theory.

PubMed

Hendriks, Annemieke L; Barnes-Holmes, Yvonne; McEnteggart, Ciara; De Mey, Hubert R A; Janssen, Gwenny T L; Egger, Jos I M

2016-01-01

Impairments in social cognition and perspective-taking play an important role in the psychopathology and social functioning of individuals with social anxiety, autism, or schizophrenia-spectrum disorders, among other clinical presentations. Perspective-taking has mostly been studied using the concept of Theory of Mind (ToM), which describes the sequential development of these skills in young children, as well as clinical populations experiencing perspective-taking difficulties. Several studies mention positive results of ToM based training programs; however, the precise processes involved in the achievement of these improvements are difficult to determine. Relational Frame Theory (RFT) is a modern behavioral account of complex cognitive functions, and is argued to provide a more precise approach to the assessment and training of perspective-taking, among other relational skills. Results of RFT-based studies of perspective-taking in developmental and clinical settings are discussed. The development of training methods targeting perspective-taking deficits from an RFT point of view appears to provide promising applications for the enhancement of current treatments of people with social-cognitive dysfunctions.

WFIRST: Astrometry with the Wide-Field Imager

NASA Astrophysics Data System (ADS)

Bellini, Andrea; WFIRST Astrometry Working Group

2018-01-01

The wide field of view and stable, sharp images delivered by WFIRST's Wide-Field Imager make it an excellent instrument for astrometry, one of five major discovery areas identified in the 2010 Decadal Survey. Compared to the Hubble Space Telescope, WFIRST's wider field of view with similar image quality will provide hundreds more astrometric targets per image as well as background galaxies and stars with precise positions in the Gaia catalog. In addition, WFIRST will operate in the infrared, a wavelength regime where the most precise astrometry has so far been achieved with adaptive optics images from large ground-based telescopes. WFIRST will provide at least a factor of three improvement in astrometry over the current state of the art in this wavelength range, while spanning a field of view thousands of times larger. WFIRST is thus poised to make major contributions to multiple science topics in which astrometry plays an important role, without major alterations to the planned mission or instrument. We summarize a few of the most compelling science cases where WFIRST astrometry could prove transformational.

Authentication Based on Pole-zero Models of Signature Velocity

PubMed Central

Rashidi, Saeid; Fallah, Ali; Towhidkhah, Farzad

2013-01-01

With the increase of communication and financial transaction through internet, on-line signature verification is an accepted biometric technology for access control and plays a significant role in authenticity and authorization in modernized society. Therefore, fast and precise algorithms for the signature verification are very attractive. The goal of this paper is modeling of velocity signal that pattern and properties is stable for persons. With using pole-zero models based on discrete cosine transform, precise method is proposed for modeling and then features is founded from strokes. With using linear, parzen window and support vector machine classifiers, the signature verification technique was tested with a large number of authentic and forgery signatures and has demonstrated the good potential of this technique. The signatures are collected from three different database include a proprietary database, the SVC2004 and the Sabanci University signature database benchmark databases. Experimental results based on Persian, SVC2004 and SUSIG databases show that our method achieves an equal error rate of 5.91%, 5.62% and 3.91% in the skilled forgeries, respectively. PMID:24696797

Assessment of Gamma-Ray Spectra Analysis Method Utilizing the Fireworks Algorithm for various Error Measures

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

Alamaniotis, Miltiadis; Tsoukalas, Lefteri H.

2018-01-01

Significant role in enhancing nuclear nonproliferation plays the analysis of obtained data and the inference of the presence or not of special nuclear materials in them. Among various types of measurements, gamma-ray spectra is the widest used type of data utilized for analysis in nonproliferation. In this chapter, a method that employs the fireworks algorithm (FWA) for analyzing gamma-ray spectra aiming at detecting gamma signatures is presented. In particular FWA is utilized to fit a set of known signatures to a measured spectrum by optimizing an objective function, with non-zero coefficients expressing the detected signatures. FWA is tested on amore » set of experimentally obtained measurements and various objective functions -MSE, RMSE, Theil-2, MAE, MAPE, MAP- with results exhibiting its potential in providing high accuracy and high precision of detected signatures. Furthermore, FWA is benchmarked against genetic algorithms, and multiple linear regression with results exhibiting its superiority over the rest tested algorithms with respect to precision for MAE, MAPE and MAP measures.« less

Surface micro- and nano-texturing of stainless steel by femtosecond laser for the control of cell migration.

PubMed

Martínez-Calderon, M; Manso-Silván, M; Rodríguez, A; Gómez-Aranzadi, M; García-Ruiz, J P; Olaizola, S M; Martín-Palma, R J

2016-11-02

The precise control over the interaction between cells and the surface of materials plays a crucial role in optimizing the integration of implanted biomaterials. In this regard, material surface with controlled topographic features at the micro- and nano-scales has been proved to affect the overall cell behavior and therefore the final osseointegration of implants. Within this context, femtosecond (fs) laser micro/nano machining technology was used in this work to modify the surface structure of stainless steel aiming at controlling cell adhesion and migration. The experimental results show that cells tend to attach and preferentially align to the laser-induced nanopatterns oriented in a specific direction. Accordingly, the laser-based fabrication method here described constitutes a simple, clean, and scalable technique which allows a precise control of the surface nano-patterning process and, subsequently, enables the control of cell adhesion, migration, and polarization. Moreover, since our surface-patterning approach does not involve any chemical treatments and is performed in a single step process, it could in principle be applied to most metallic materials.

Biopharmaceuticals: From peptide to drug

NASA Astrophysics Data System (ADS)

Hannappel, Margarete

2017-08-01

Biologics are therapeutic proteins or peptides that are produced by means of biological processes within living organisms and cells. They are highly specific molecules and play a crucial role as therapeutics for the treatment of severe and chronic diseases (e.g. cancer, rheumatoid arthritis, diabetes, autoimmune disorders). The development of new biologics and biologics-based drugs gains more and more importance in the fight against various diseases. A short overview on biotherapeutical drug development is given. Cone snails are a large group of poisonous, predatory sea snails with more than 700 species. They use a very powerful venom which rapidly inactivates and paralyzes their prey. Most bioactive venom components are small peptides (conotoxins, conopeptides) which are precisely directed towards a specific target (e.g. ion channel, receptors). Due to their small size, their precision and speed of action, naturally occurring cone snail venom peptides represent an attractive source for the identification and design of novel biological drug entities. The Jagna cone snail project is an encouraging initiative to map the ecological variety of cone snails around the island of Bohol (Philippines) and to conserve the biological information for potential future application.

Surface micro- and nano-texturing of stainless steel by femtosecond laser for the control of cell migration

PubMed Central

Martínez-Calderon, M.; Manso-Silván, M.; Rodríguez, A.; Gómez-Aranzadi, M.; García-Ruiz, J. P.; Olaizola, S. M.; Martín-Palma, R. J.

2016-01-01

The precise control over the interaction between cells and the surface of materials plays a crucial role in optimizing the integration of implanted biomaterials. In this regard, material surface with controlled topographic features at the micro- and nano-scales has been proved to affect the overall cell behavior and therefore the final osseointegration of implants. Within this context, femtosecond (fs) laser micro/nano machining technology was used in this work to modify the surface structure of stainless steel aiming at controlling cell adhesion and migration. The experimental results show that cells tend to attach and preferentially align to the laser-induced nanopatterns oriented in a specific direction. Accordingly, the laser-based fabrication method here described constitutes a simple, clean, and scalable technique which allows a precise control of the surface nano-patterning process and, subsequently, enables the control of cell adhesion, migration, and polarization. Moreover, since our surface-patterning approach does not involve any chemical treatments and is performed in a single step process, it could in principle be applied to most metallic materials. PMID:27805063

Brain MR image segmentation using NAMS in pseudo-color.

PubMed

Li, Hua; Chen, Chuanbo; Fang, Shaohong; Zhao, Shengrong

2017-12-01

Image segmentation plays a crucial role in various biomedical applications. In general, the segmentation of brain Magnetic Resonance (MR) images is mainly used to represent the image with several homogeneous regions instead of pixels for surgical analyzing and planning. This paper proposes a new approach for segmenting MR brain images by using pseudo-color based segmentation with Non-symmetry and Anti-packing Model with Squares (NAMS). First of all, the NAMS model is presented. The model can represent the image with sub-patterns to keep the image content and largely reduce the data redundancy. Second, the key idea is proposed that convert the original gray-scale brain MR image into a pseudo-colored image and then segment the pseudo-colored image with NAMS model. The pseudo-colored image can enhance the color contrast in different tissues in brain MR images, which can improve the precision of segmentation as well as directly visual perceptional distinction. Experimental results indicate that compared with other brain MR image segmentation methods, the proposed NAMS based pseudo-color segmentation method performs more excellent in not only segmenting precisely but also saving storage.

The Great War as a Crucial Point in the History of Russian Science and Technology.

PubMed

Saprykin, Dmitry L

2016-01-01

The paper is devoted to one of the most important and, at the same time, relatively unexplored phases in the history of Russian science and technology. The Great War coincided with the beginning of a heyday in science, engineering education, and technology in Russia. It was precisely the time in which Russia's era of "Big Science" was emer- ging. Many Russian and Soviet technical projects and scientific schools were rooted in the time of the Great War. The "engineerization" of science and a "physical-technical" way of thinking had already begun before the war. But it was precisely the war which encouraged a large proportion of the Russian academic community to take part in industrial projects. Academics also played a significant role in developing concepts and implementing strategic plans during the Great War. This article also discusses how the organization of science and the academic community was transformed during, and after, the Great War. And it looks at the impact that war had on Russia's participation in the international scientific community.

Recovering the 3d Pose and Shape of Vehicles from Stereo Images

NASA Astrophysics Data System (ADS)

Coenen, M.; Rottensteiner, F.; Heipke, C.

2018-05-01

The precise reconstruction and pose estimation of vehicles plays an important role, e.g. for autonomous driving. We tackle this problem on the basis of street level stereo images obtained from a moving vehicle. Starting from initial vehicle detections, we use a deformable vehicle shape prior learned from CAD vehicle data to fully reconstruct the vehicles in 3D and to recover their 3D pose and shape. To fit a deformable vehicle model to each detection by inferring the optimal parameters for pose and shape, we define an energy function leveraging reconstructed 3D data, image information, the vehicle model and derived scene knowledge. To minimise the energy function, we apply a robust model fitting procedure based on iterative Monte Carlo model particle sampling. We evaluate our approach using the object detection and orientation estimation benchmark of the KITTI dataset (Geiger et al., 2012). Our approach can deal with very coarse pose initialisations and we achieve encouraging results with up to 82 % correct pose estimations. Moreover, we are able to deliver very precise orientation estimation results with an average absolute error smaller than 4°.

Controlled Living Nanowire Growth: Precise Control over the Morphology and Optical Properties of AgAuAg Bimetallic Nanowires

PubMed Central

2015-01-01

Inspired by the concept of living polymerization reaction, we are able to produce silver–gold–silver nanowires with a precise control over their total length and plasmonic properties by establishing a constant silver deposition rate on the tips of penta-twinned gold nanorods used as seed cores. Consequently, the length of the wires increases linearly in time. Starting with ∼210 nm × 32 nm gold cores, we produce nanowire lengths up to several microns in a highly controlled manner, with a small self-limited increase in thickness of ∼4 nm, corresponding to aspect ratios above 100, whereas the low polydispersity of the product allows us to detect up to nine distinguishable plasmonic resonances in a single colloidal solution. We analyze the spatial distribution and the nature of the plasmons by electron energy loss spectroscopy and obtain excellent agreement between measurements and electromagnetic simulations, clearly demonstrating that the presence of the gold core plays a marginal role, except for relatively short wires or high-energy modes. PMID:26134470

Elevation of transforming growth factor beta (TGFbeta) and its downstream mediators in subcutaneous foreign body capsule tissue.

PubMed

Li, Allen G; Quinn, Matthew J; Siddiqui, Yasmin; Wood, Michael D; Federiuk, Isaac F; Duman, Heather M; Ward, W Kenneth

2007-08-01

Foreign body encapsulation represents a chronic fibrotic response and has been a major obstacle that reduces the useful life of implanted biomedical devices. The precise mechanism underlying such an encapsulation is still unknown. We hypothesized that, considering its central role in many other fibrotic conditions, transforming growth factor beta (TGFbeta) may play an important role during the formation of foreign body capsule (FBC). In the present study, we implanted mock sensors in rats subcutaneously and excised FBC samples at day 7, 21, and 48-55 postimplantation. The most abundant TGFbeta isoform in all tissues was TGFbeta1, which was expressed minimally in control tissue. The expression of both TGFbeta1 RNA and protein was significantly increased in FBC tissues at all time points, with the highest level in day 7 FBC. The number of cells stained for phosphorylated Smad2, an indication of activated TGFbeta signaling, paralleled the expression of TGFbeta. A similar dynamic change was also observed in the numbers of FBC myofibroblasts, which in response to TGFbeta, differentiate from quiescent fibroblasts and synthesize collagen. Type I collagen, the most prominent downstream target of TGFbeta in fibrosis, was found in abundance in the FBC, especially during the latter time periods. We suggest that TGFbeta plays an important role in the FBC formation. Inhibition of TGFbeta signaling could be a promising strategy in the prevention of FBC formation, thereby extending the useful life of subcutaneous implants.

Genomic islands 1 and 2 play key roles in the evolution of extensively drug-resistant ST235 isolates of Pseudomonas aeruginosa

PubMed Central

Scott, Martin; Worden, Paul; Huntington, Peter; Hudson, Bernard; Karagiannis, Thomas; Charles, Ian G.; Djordjevic, Steven P.

2016-01-01

Pseudomonas aeruginosa are noscomially acquired, opportunistic pathogens that pose a major threat to the health of burns patients and the immunocompromised. We sequenced the genomes of P. aeruginosa isolates RNS_PA1, RNS_PA46 and RNS_PAE05, which displayed resistance to almost all frontline antibiotics, including gentamicin, piperacillin, timentin, meropenem, ceftazidime and colistin. We provide evidence that the isolates are representatives of P. aeruginosa sequence type (ST) 235 and carry Tn6162 and Tn6163 in genomic islands 1 (GI1) and 2 (GI2), respectively. GI1 disrupts the endA gene at precisely the same chromosomal location as in P. aeruginosa strain VR-143/97, of unknown ST, creating an identical CA direct repeat. The class 1 integron associated with Tn6163 in GI2 carries a blaGES-5–aacA4–gcuE15–aphA15 cassette array conferring resistance to carbapenems and aminoglycosides. GI2 is flanked by a 12 nt direct repeat motif, abuts a tRNA-gly gene, and encodes proteins with putative roles in integration, conjugative transfer as well as integrative conjugative element-specific proteins. This suggests that GI2 may have evolved from a novel integrative conjugative element. Our data provide further support to the hypothesis that genomic islands play an important role in de novo evolution of multiple antibiotic resistance phenotypes in P. aeruginosa. PMID:26962050

HTLV-1 HBZ Viral Protein: A Key Player in HTLV-1 Mediated Diseases.

PubMed

Baratella, Marco; Forlani, Greta; Accolla, Roberto S

2017-01-01

Human T cell leukemia virus type 1 (HTLV-1) is an oncogenic human retrovirus that has infected 10-15 million people worldwide. After a long latency, 3-5% of infected individuals will develop either a severe malignancy of CD4+ T cells, known as Adult T-cell Leukemia (ATL) or a chronic and progressive inflammatory disease of the nervous system designated Tropical Spastic Paraparesis/HTLV-1-Associated Myelopathy (HAM/TSP). The precise mechanism behind HTLV-1 pathogenesis still remains elusive. Two viral regulatory proteins, Tax-1 and HTLV-1 bZIP factor (HBZ) are thought to play a critical role in HTLV-1-associated diseases. Tax-1 is mainly involved in the onset of neoplastic transformation and in elicitation of the host's inflammatory responses; its expression may be lost during cell clonal proliferation and oncogenesis. Conversely, HBZ remains constantly expressed in all patients with ATL, playing a role in the proliferation and maintenance of leukemic cells. Recent studies have shown that the subcellular distribution of HBZ protein differs in the two pathologies: it is nuclear with a speckled-like pattern in leukemic cells and is cytoplasmic in cells from HAM/TSP patients. Thus, HBZ expression and distribution could be critical in the progression of HTLV-1 infection versus the leukemic state or the inflammatory disease. Here, we reviewed recent findings on the role of HBZ in HTLV-1 related diseases, highlighting the new perspectives open by the possibility of studying the physiologic expression of endogenous protein in primary infected cells.

Dysregulation of Ezrin phosphorylation prevents metastasis and alters cellular metabolism in osteosarcoma

PubMed Central

Ren, Ling; Hong, Sung-Hyeok; Chen, Qing-Rong; Briggs, Joseph; Cassavaugh, Jessica; Srinivasan, Satish; Lizardo, Michael M.; Mendoza, Arnulfo; Xia, Ashley Y.; Avadhani, Narayan; Khan, Javed; Khanna, Chand

2013-01-01

Ezrin links the plasma membrane to the actin cytoskeleton where it plays a pivotal role in the metastatic progression of several human cancers (1, 2), however, the precise mechanistic basis for its role remains unknown. Here we define transitions between active (phosphorylated open) and inactive (dephosphorylated closed) forms of Ezrin that occur during metastatic progression in osteosarcoma. In our evaluation of these conformations we expressed C-terminal mutant forms of Ezrin that are open (phosphomimetic T567D) or closed (phosphodeficient T567A) and compared their biological characteristics to full length wild-type Ezrin in osteosarcoma cells. Unexpectedly, cells expressing open, active Ezrin could form neither primary orthotopic tumors nor lung metastases. In contrast, cells expressing closed, inactive Ezrin were also deficient in metastasis but were unaffected in their capacity for primary tumor growth. By imaging single metastatic cells in the lung, we found that cells expressing either open or closed Ezrin displayed increased levels of apoptosis early after their arrival in the lung. Gene expression analysis suggested dysregulation of genes that are functionally linked to carbohydrate and amino acid metabolism. In particular, cells expressing closed, inactive Ezrin exhibited reduced lactate production and basal or ATP-dependent oxygen consumption. Collectively, our results suggest that dynamic regulation of Ezrin phosphorylation at amino acid T567 that controls structural transitions of this protein plays a pivotal role in tumor progression and metastasis, possibly in part by altering cellular metabolism. PMID:22147261

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

Park, Sangkyu, E-mail: 49park@cku.ac.kr; Lee, Yoo Jeong; Ko, Eun Hee

Glucose metabolism is balanced by glycolysis and gluconeogenesis with precise control in the liver. The expression of genes related to glucose metabolism is regulated primarily by glucose and insulin at transcriptional level. Nuclear receptors play important roles in regulating the gene expression of glucose metabolism at transcriptional level. Some of these nuclear receptors form heterodimers with RXRs to bind to their specific regulatory elements on the target promoters. To date, three isotypes of RXRs have been identified; RXRα, RXRβ and RXRγ. However, their involvement in the interactions with other nuclear receptors in the liver remains unclear. In this study, wemore » found RXRγ is rapidly induced after feeding in the mouse liver, indicating a potential role of RXRγ in controlling glucose or lipid metabolism in the fasting–feeding cycle. In addition, RXRγ expression was upregulated by glucose in primary hepatocytes. This implies that glucose metabolism governed by RXRγ in conjunction with other nuclear receptors. The luciferase reporter assay showed that RXRγ as well as RXRα increased SREBP-1c promoter activity in hepatocytes. These results suggest that RXRγ may play an important role in tight control of glucose metabolism in the fasting–feeding cycle. - Highlights: • Refeeding increases the RXRγ expression level in mouse liver. • RXRγ expression is induced by high glucose condition in primary hepatocytes. • RXRγ and LXRα have synergistic effect on SREBP-1c promoter activity. • RXRγ binds to LXRE(-299/-280) located within SREBP-1c promoter region and interacts with LXRα.« less

Slow-Wave Sleep-Imposed Replay Modulates Both Strength and Precision of Memory

PubMed Central

2014-01-01

Odor perception is hypothesized to be an experience-dependent process involving the encoding of odor objects by distributed olfactory cortical ensembles. Olfactory cortical neurons coactivated by a specific pattern of odorant evoked input become linked through association fiber synaptic plasticity, creating a template of the familiar odor. In this way, experience and memory play an important role in odor perception and discrimination. In other systems, memory consolidation occurs partially via slow-wave sleep (SWS)-dependent replay of activity patterns originally evoked during waking. SWS is ideal for replay given hyporesponsive sensory systems, and thus reduced interference. Here, using artificial patterns of olfactory bulb stimulation in a fear conditioning procedure in the rat, we tested the effects of imposed post-training replay during SWS and waking on strength and precision of pattern memory. The results show that imposed replay during post-training SWS enhanced the subsequent strength of memory, whereas the identical replay during waking induced extinction. The magnitude of this enhancement was dependent on the timing of imposed replay relative to cortical sharp-waves. Imposed SWS replay of stimuli, which differed from the conditioned stimulus, did not affect conditioned stimulus memory strength but induced generalization of the fear memory to novel artificial patterns. Finally, post-training disruption of piriform cortex intracortical association fiber synapses, hypothesized to be critical for experience-dependent odor coding, also impaired subsequent memory precision but not strength. These results suggest that SWS replay in the olfactory cortex enhances memory consolidation, and that memory precision is dependent on the fidelity of that replay. PMID:24719093

Magnetic resonance imaging of the calcaneus: preliminary assessment of trabecular bone-dependent regional variations in marrow relaxation time compared with dual X-ray absorptiometry

NASA Technical Reports Server (NTRS)

Guglielmi, G.; Selby, K.; Blunt, B. A.; Jergas, M.; Newitt, D. C.; Genant, H. K.; Majumdar, S.

1996-01-01

RATIONALE AND OBJECTIVES: Marrow transverse relaxation time (T2*) in magnetic resonance (MR) imaging may be related to the density and structure of the surrounding trabecular network. We investigated regional variations of T2* in the human calcaneus and compared the findings with bone mineral density (BMD), as measured by dual X-ray absorpiometry (DXA). Short- and long-term precisions were evaluated first to determine whether MR imaging would be useful for the clinical assessment of disease status and progression in osteoporosis. METHODS: Gradient-recalled echo MR images of the calcaneus were acquired at 1.5 T from six volunteers. Measurements of T2* were compared with BMD and (for one volunteer) conventional radiography. RESULTS: T2* values showed significant regional variation; they typically were shortest in the superior region of the calcaneus. There was a linear correlation between MR and DXA measurements (r = .66 for 1/T2* versus BMD). Differences in T2* attributable to variations in analysis region-of-interest placement were not significant for five of the six volunteers. Sagittal MR images had short- and long-term precision errors of 4.2% and 3.3%, respectively. For DXA, the precision was 1.3% (coefficient of variation). CONCLUSION: MR imaging may be useful for trabecular bone assessment in the calcaneus. However, given the large regional variations in bone density and structure, the choice of an ROI is likely to play a major role in the accuracy, precision, and overall clinical efficacy of T2* measurements.

How to Use (Not Abuse) Role Plays.

ERIC Educational Resources Information Center

Wright, Van O.

1989-01-01

Discusses the use of role plays in training for human communication skills, sales skills, and management skills. Rules for the application of role plays are given, steps in designing role plays are described, typical role play structures are explained, and materials for instructors and participants are discussed. (LRW)

Automatical and accurate segmentation of cerebral tissues in fMRI dataset with combination of image processing and deep learning

NASA Astrophysics Data System (ADS)

Kong, Zhenglun; Luo, Junyi; Xu, Shengpu; Li, Ting

2018-02-01

Image segmentation plays an important role in medical science. One application is multimodality imaging, especially the fusion of structural imaging with functional imaging, which includes CT, MRI and new types of imaging technology such as optical imaging to obtain functional images. The fusion process require precisely extracted structural information, in order to register the image to it. Here we used image enhancement, morphometry methods to extract the accurate contours of different tissues such as skull, cerebrospinal fluid (CSF), grey matter (GM) and white matter (WM) on 5 fMRI head image datasets. Then we utilized convolutional neural network to realize automatic segmentation of images in deep learning way. Such approach greatly reduced the processing time compared to manual and semi-automatic segmentation and is of great importance in improving speed and accuracy as more and more samples being learned. The contours of the borders of different tissues on all images were accurately extracted and 3D visualized. This can be used in low-level light therapy and optical simulation software such as MCVM. We obtained a precise three-dimensional distribution of brain, which offered doctors and researchers quantitative volume data and detailed morphological characterization for personal precise medicine of Cerebral atrophy/expansion. We hope this technique can bring convenience to visualization medical and personalized medicine.

An Improved Interferometric Calibration Method Based on Independent Parameter Decomposition

NASA Astrophysics Data System (ADS)

Fan, J.; Zuo, X.; Li, T.; Chen, Q.; Geng, X.

2018-04-01

Interferometric SAR is sensitive to earth surface undulation. The accuracy of interferometric parameters plays a significant role in precise digital elevation model (DEM). The interferometric calibration is to obtain high-precision global DEM by calculating the interferometric parameters using ground control points (GCPs). However, interferometric parameters are always calculated jointly, making them difficult to decompose precisely. In this paper, we propose an interferometric calibration method based on independent parameter decomposition (IPD). Firstly, the parameters related to the interferometric SAR measurement are determined based on the three-dimensional reconstruction model. Secondly, the sensitivity of interferometric parameters is quantitatively analyzed after the geometric parameters are completely decomposed. Finally, each interferometric parameter is calculated based on IPD and interferometric calibration model is established. We take Weinan of Shanxi province as an example and choose 4 TerraDEM-X image pairs to carry out interferometric calibration experiment. The results show that the elevation accuracy of all SAR images is better than 2.54 m after interferometric calibration. Furthermore, the proposed method can obtain the accuracy of DEM products better than 2.43 m in the flat area and 6.97 m in the mountainous area, which can prove the correctness and effectiveness of the proposed IPD based interferometric calibration method. The results provide a technical basis for topographic mapping of 1 : 50000 and even larger scale in the flat area and mountainous area.

Insulin Resistance: Regression and Clustering

PubMed Central

Yoon, Sangho; Assimes, Themistocles L.; Quertermous, Thomas; Hsiao, Chin-Fu; Chuang, Lee-Ming; Hwu, Chii-Min; Rajaratnam, Bala; Olshen, Richard A.

2014-01-01

In this paper we try to define insulin resistance (IR) precisely for a group of Chinese women. Our definition deliberately does not depend upon body mass index (BMI) or age, although in other studies, with particular random effects models quite different from models used here, BMI accounts for a large part of the variability in IR. We accomplish our goal through application of Gauss mixture vector quantization (GMVQ), a technique for clustering that was developed for application to lossy data compression. Defining data come from measurements that play major roles in medical practice. A precise statement of what the data are is in Section 1. Their family structures are described in detail. They concern levels of lipids and the results of an oral glucose tolerance test (OGTT). We apply GMVQ to residuals obtained from regressions of outcomes of an OGTT and lipids on functions of age and BMI that are inferred from the data. A bootstrap procedure developed for our family data supplemented by insights from other approaches leads us to believe that two clusters are appropriate for defining IR precisely. One cluster consists of women who are IR, and the other of women who seem not to be. Genes and other features are used to predict cluster membership. We argue that prediction with “main effects” is not satisfactory, but prediction that includes interactions may be. PMID:24887437

Research on registration algorithm for check seal verification

NASA Astrophysics Data System (ADS)

Wang, Shuang; Liu, Tiegen

2008-03-01

Nowadays seals play an important role in China. With the development of social economy, the traditional method of manual check seal identification can't meet the need s of banking transactions badly. This paper focus on pre-processing and registration algorithm for check seal verification using theory of image processing and pattern recognition. First of all, analyze the complex characteristics of check seals. To eliminate the difference of producing conditions and the disturbance caused by background and writing in check image, many methods are used in the pre-processing of check seal verification, such as color components transformation, linearity transform to gray-scale image, medium value filter, Otsu, close calculations and labeling algorithm of mathematical morphology. After the processes above, the good binary seal image can be obtained. On the basis of traditional registration algorithm, a double-level registration method including rough and precise registration method is proposed. The deflection angle of precise registration method can be precise to 0.1°. This paper introduces the concepts of difference inside and difference outside and use the percent of difference inside and difference outside to judge whether the seal is real or fake. The experimental results of a mass of check seals are satisfied. It shows that the methods and algorithmic presented have good robustness to noise sealing conditions and satisfactory tolerance of difference within class.

A Miniaturized Colorimeter with a Novel Design and High Precision for Photometric Detection.

PubMed

Yan, Jun-Chao; Chen, Yan; Pang, Yu; Slavik, Jan; Zhao, Yun-Fei; Wu, Xiao-Ming; Yang, Yi; Yang, Si-Fan; Ren, Tian-Ling

2018-03-08

Water quality detection plays an increasingly important role in environmental protection. In this work, a novel colorimeter based on the Beer-Lambert law was designed for chemical element detection in water with high precision and miniaturized structure. As an example, the colorimeter can detect phosphorus, which was accomplished in this article to evaluate the performance. Simultaneously, a modified algorithm was applied to extend the linear measurable range. The colorimeter encompassed a near infrared laser source, a microflow cell based on microfluidic technology and a light-sensitive detector, then Micro-Electro-Mechanical System (MEMS) processing technology was used to form a stable integrated structure. Experiments were performed based on the ammonium molybdate spectrophotometric method, including the preparation of phosphorus standard solution, reducing agent, chromogenic agent and color reaction. The device can obtain a wide linear response range (0.05 mg/L up to 7.60 mg/L), a wide reliable measuring range up to 10.16 mg/L after using a novel algorithm, and a low limit of detection (0.02 mg/L). The size of flow cell in this design is 18 mm × 2.0 mm × 800 μm, obtaining a low reagent consumption of 0.004 mg ascorbic acid and 0.011 mg ammonium molybdate per determination. Achieving these advantages of miniaturized volume, high precision and low cost, the design can also be used in automated in situ detection.

A Miniaturized Colorimeter with a Novel Design and High Precision for Photometric Detection

PubMed Central

Chen, Yan; Pang, Yu; Slavik, Jan; Zhao, Yun-Fei; Wu, Xiao-Ming; Yang, Yi; Yang, Si-Fan; Ren, Tian-Ling

2018-01-01

Water quality detection plays an increasingly important role in environmental protection. In this work, a novel colorimeter based on the Beer-Lambert law was designed for chemical element detection in water with high precision and miniaturized structure. As an example, the colorimeter can detect phosphorus, which was accomplished in this article to evaluate the performance. Simultaneously, a modified algorithm was applied to extend the linear measurable range. The colorimeter encompassed a near infrared laser source, a microflow cell based on microfluidic technology and a light-sensitive detector, then Micro-Electro-Mechanical System (MEMS) processing technology was used to form a stable integrated structure. Experiments were performed based on the ammonium molybdate spectrophotometric method, including the preparation of phosphorus standard solution, reducing agent, chromogenic agent and color reaction. The device can obtain a wide linear response range (0.05 mg/L up to 7.60 mg/L), a wide reliable measuring range up to 10.16 mg/L after using a novel algorithm, and a low limit of detection (0.02 mg/L). The size of flow cell in this design is 18 mm × 2.0 mm × 800 μm, obtaining a low reagent consumption of 0.004 mg ascorbic acid and 0.011 mg ammonium molybdate per determination. Achieving these advantages of miniaturized volume, high precision and low cost, the design can also be used in automated in situ detection. PMID:29518059

The contribution of inflammasome components on macrophage response to surface nanotopography and chemistry

NASA Astrophysics Data System (ADS)

Christo, Susan; Bachhuka, Akash; Diener, Kerrilyn R.; Vasilev, Krasimir; Hayball, John D.

2016-05-01

Implantable devices have become an established part of medical practice. However, often a negative inflammatory host response can impede the integration and functionality of the device. In this paper, we interrogate the role of surface nanotopography and chemistry on the potential molecular role of the inflammasome in controlling macrophage responses. To achieve this goal we engineered model substrata having precisely controlled nanotopography of predetermined height and tailored outermost surface chemistry. Bone marrow derived macrophages (BMDM) were harvested from genetically engineered mice deficient in the inflammasome components ASC, NLRP3 and AIM2. These cells were then cultured on these nanoengineered substrata and assessed for their capacity to attach and express pro-inflammatory cytokines. Our data provide evidence that the inflammasome components ASC, NLRP3 and AIM2 play a role in regulating macrophage adhesion and activation in response to surface nanotopography and chemistry. The findings of this paper are important for understanding the inflammatory consequences caused by biomaterials and pave the way to the rational design of future implantable devices having controlled and predictable inflammatory outcomes.

Distinct Roles of PKCι/λ and PKMζ in the Initiation and Maintenance of Hippocampal Long-Term Potentiation and Memory.

PubMed

Wang, Shaoli; Sheng, Tao; Ren, Siqiang; Tian, Tian; Lu, Wei

2016-08-16

PKMζ has been proposed to be essential for maintenance of long-term potentiation (LTP) and long-term memory (LTM). However, recent data from PKMζ-knockout mice has called this role into question. Instead, the other atypical isoform, protein kinase C iota/lambda (PKCι/λ), has emerged as a potential alternative player. Therefore, the nature of the "memory molecule" maintaining learned information remains uncertain. Here, we report knockdown (KD) of PKCι/λ and PKMζ in the dorsal hippocampus and find deficits in early expression and late maintenance, respectively, during both LTP and hippocampus-dependent LTM. Sequential increases in the active form of PKCι/λ and PKMζ are detected during LTP or fear conditioning. Importantly, PKMζ, but not PKCι/λ, KD disrupts previously established LTM. Thus, PKCι/λ and PKMζ have distinct functions in LTP and memory, with PKMζ playing a specific role in memory maintenance. This relaying pattern may represent a precise molecular mechanism by which atypical PKCs regulate the different stages of memory. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Concise review: genetic dissection of hypoxia signaling pathways in normal and leukemic stem cells.

PubMed

Gezer, Deniz; Vukovic, Milica; Soga, Tomoyoshi; Pollard, Patrick J; Kranc, Kamil R

2014-06-01

Adult hematopoiesis depends on rare multipotent hematopoietic stem cells (HSCs) that self-renew and give rise to progenitor cells, which differentiate to all blood lineages. The strict regulation of the fine balance between self-renewal and differentiation is essential for normal hematopoiesis and suppression of leukemia development. HSCs and progenitor cells are commonly assumed to reside within the hypoxic BM microenvironment, however, there is no direct evidence supporting this notion. Nevertheless, HSCs and progenitors do exhibit a hypoxic profile and strongly express Hif-1α. Although hypoxia signaling pathways are thought to play important roles in adult HSC maintenance and leukemogenesis, the precise function of Hif-dependent signaling in HSCs remains to be uncovered. Here we discuss recent gain-of-function and loss-of-function studies that shed light on the complex roles of hypoxia-signaling pathways in HSCs and their niches in normal and malignant hematopoiesis. Importantly, we comment on the current and often contrasting interpretations of the role of Hif-dependent signaling in stem cell functions. © 2014 AlphaMed Press.

Structural basis for regulation of GPR56/ADGRG1 by its alternatively spliced extracellular domains

PubMed Central

Salzman, Gabriel S.; Ackerman, Sarah D.; Ding, Chen; Koide, Akiko; Leon, Katherine; Luo, Rong; Stoveken, Hannah M.; Fernandez, Celia G.; Tall, Gregory G.; Piao, Xianhua; Monk, Kelly R.; Koide, Shohei; Araç, Demet

2016-01-01

Summary Adhesion G-protein-coupled receptors (aGPCRs) play critical roles in diverse neurobiological processes including brain development, synaptogenesis, and myelination. aGPCRs have large alternatively spliced extracellular regions (ECRs) that likely mediate intercellular signaling; however, the precise roles of ECRs remain unclear. The aGPCR GPR56/ADGRG1 regulates both oligodendrocyte and cortical development. Accordingly, human GPR56 mutations cause myelination defects and brain malformations. Here, we determined the crystal structure of the GPR56 ECR, the first structure of any complete aGPCR ECR, in complex with an inverse-agonist monobody, revealing a GPCR-Autoproteolysis-Inducing domain and a previously unidentified domain that we term Pentraxin/Laminin/neurexin/sex-hormone-binding-globulin-Like (PLL). Strikingly, PLL domain deletion caused increased signaling and characterizes a GPR56 splice variant. Finally, we show that an evolutionarily conserved residue in the PLL domain is critical for oligodendrocyte development in vivo. Thus, our results suggest that the GPR56 ECR has unique and multifaceted regulatory functions, providing novel insights into aGPCR roles in neurobiology. PMID:27657451

Managing Incidental Pancreatic Cysts.

PubMed

Phan, Jennifer; Raman Muthusamy, V

2018-06-09

The goal of this review is to critically analyze the current literature regarding the management of incidental pancreatic cysts. Given their increased rates of detection due to the frequent use of cross-sectional imaging, correctly identifying the subset of high risk lesions that are appropriate for surgical resection is critical. However, the existing consensus and societal guidelines discussed in this review lack high quality data to create evidence-based recommendations, making achieving this important aim challenging. Several recent studies have focused on the natural history of pancreatic cysts and defining the role of endoscopic ultrasound, which remains unclear. EUS-guided diagnostic tools include molecular analysis of obtained fluid; EUS-guided FNA, FNB, and intracystic forceps biopsy of the cyst wall; and confocal endomicroscopy. While their precise role in diagnosing pancreatic cystic neoplasms remains to be defined, they represent promising innovations that may play a future role in cyst assessment and management. Large, long-term, prospective studies of incidentally identified pancreatic cysts are essential to fully understand their natural history and potential for neoplastic progression. Given the absence of such data at present, an individualized patient approach is recommended.

The SNARE Protein Syntaxin 3 Confers Specificity for Polarized Axonal Trafficking in Neurons

PubMed Central

Soo Hoo, Linda; Banna, Chris D.; Radeke, Carolyn M.; Sharma, Nikunj; Albertolle, Mary E.; Low, Seng Hui; Weimbs, Thomas; Vandenberg, Carol A.

2016-01-01

Cell polarity and precise subcellular protein localization are pivotal to neuronal function. The SNARE machinery underlies intracellular membrane fusion events, but its role in neuronal polarity and selective protein targeting remain unclear. Here we report that syntaxin 3 is involved in orchestrating polarized trafficking in cultured rat hippocampal neurons. We show that syntaxin 3 localizes to the axonal plasma membrane, particularly to axonal tips, whereas syntaxin 4 localizes to the somatodendritic plasma membrane. Disruption of a conserved N-terminal targeting motif, which causes mislocalization of syntaxin 3, results in coincident mistargeting of the axonal cargos neuron-glia cell adhesion molecule (NgCAM) and neurexin, but not transferrin receptor, a somatodendritic cargo. Similarly, RNAi-mediated knockdown of endogenous syntaxin 3 leads to partial mistargeting of NgCAM, demonstrating that syntaxin 3 plays an important role in its targeting. Additionally, overexpression of syntaxin 3 results in increased axonal growth. Our findings suggest an important role for syntaxin 3 in maintaining neuronal polarity and in the critical task of selective trafficking of membrane protein to axons. PMID:27662481

The SNARE Protein Syntaxin 3 Confers Specificity for Polarized Axonal Trafficking in Neurons.

PubMed

Soo Hoo, Linda; Banna, Chris D; Radeke, Carolyn M; Sharma, Nikunj; Albertolle, Mary E; Low, Seng Hui; Weimbs, Thomas; Vandenberg, Carol A

Cell polarity and precise subcellular protein localization are pivotal to neuronal function. The SNARE machinery underlies intracellular membrane fusion events, but its role in neuronal polarity and selective protein targeting remain unclear. Here we report that syntaxin 3 is involved in orchestrating polarized trafficking in cultured rat hippocampal neurons. We show that syntaxin 3 localizes to the axonal plasma membrane, particularly to axonal tips, whereas syntaxin 4 localizes to the somatodendritic plasma membrane. Disruption of a conserved N-terminal targeting motif, which causes mislocalization of syntaxin 3, results in coincident mistargeting of the axonal cargos neuron-glia cell adhesion molecule (NgCAM) and neurexin, but not transferrin receptor, a somatodendritic cargo. Similarly, RNAi-mediated knockdown of endogenous syntaxin 3 leads to partial mistargeting of NgCAM, demonstrating that syntaxin 3 plays an important role in its targeting. Additionally, overexpression of syntaxin 3 results in increased axonal growth. Our findings suggest an important role for syntaxin 3 in maintaining neuronal polarity and in the critical task of selective trafficking of membrane protein to axons.

GSK3 Inhibitor-BIO Regulates Proliferation of Immortalized Pancreatic Mesenchymal Stem Cells (iPMSCs)

PubMed Central

Cao, Hui; Chu, Yuankui; Lv, Xiao; Qiu, Pubin; Liu, Chao; Zhang, Huiru; Li, Dan; Peng, Sha; Dou, Zhongying; Hua, Jinlian

2012-01-01

Background The small molecule 6-bromoindirubin-30-oxime (BIO), a glycogen synthase kinase 3 (GSK3) inhibitor, is a pharmacological agent known to maintain self-renewal in human and mouse embryonic stem cells (ESCs). However, the precise role of GSK3 in immortalized pancreatic mesenchymal stem cells (iPMSCs) growth and survival is not completely understood at present. Results To determine whether this molecule is involved in controlling the proliferation of iPMSCs, we examined the effect of BIO on iPMSCs. We found that the inactivation of GSK3 by BIO can robustly stimulate iPMSCs proliferation and mass formation as shown by QRT-PCR, western blotting, 5-Bromo-2-deoxyuridine (BrdU) immunostaining assay and tunel assay. However, we did not find the related roles of BIO on β cell differentiation by immunostaining, QRT-PCR assay, glucose-stimulated insulin release and C-peptide content analysis. Conclusions These results suggest that BIO plays a key role in the regulation of cell mass proliferation and maintenance of the undifferentiated state of iPMSCs. PMID:22384031

Exploring Human Diseases and Biological Mechanisms by Protein Structure Prediction and Modeling.

PubMed

Wang, Juexin; Luttrell, Joseph; Zhang, Ning; Khan, Saad; Shi, NianQing; Wang, Michael X; Kang, Jing-Qiong; Wang, Zheng; Xu, Dong

2016-01-01

Protein structure prediction and modeling provide a tool for understanding protein functions by computationally constructing protein structures from amino acid sequences and analyzing them. With help from protein prediction tools and web servers, users can obtain the three-dimensional protein structure models and gain knowledge of functions from the proteins. In this chapter, we will provide several examples of such studies. As an example, structure modeling methods were used to investigate the relation between mutation-caused misfolding of protein and human diseases including epilepsy and leukemia. Protein structure prediction and modeling were also applied in nucleotide-gated channels and their interaction interfaces to investigate their roles in brain and heart cells. In molecular mechanism studies of plants, rice salinity tolerance mechanism was studied via structure modeling on crucial proteins identified by systems biology analysis; trait-associated protein-protein interactions were modeled, which sheds some light on the roles of mutations in soybean oil/protein content. In the age of precision medicine, we believe protein structure prediction and modeling will play more and more important roles in investigating biomedical mechanism of diseases and drug design.

Development of Young Adults' Fine Motor Skills when Learning to Play Percussion Instruments

ERIC Educational Resources Information Center

Gzibovskis, Talis; Marnauza, Mara

2012-01-01

When playing percussion instruments, the main activity is done with the help of a motion or motor skills; to perform it, developed fine motor skills are necessary: the speed and precision of fingers, hands and palms. The aim of the research was to study and test the development of young adults' fine motor skills while learning to play percussion…

Dual role of Brg chromatin remodeling factor in Sonic hedgehog signaling during neural development.

PubMed

Zhan, Xiaoming; Shi, Xuanming; Zhang, Zilai; Chen, Yu; Wu, Jiang I

2011-08-02

Sonic hedgehog (Shh) signaling plays diverse roles during animal development and adult tissue homeostasis through differential regulation of Gli family transcription factors. Dysregulated Shh signaling activities have been linked to birth defects and tumorigenesis. Here we report that Brg, an ATP-dependent chromatin remodeling factor, has dual functions in regulating Shh target gene expression. Using a Brg conditional deletion in Shh-responding neural progenitors and fibroblasts, we demonstrate that Brg is required both for repression of the basal expression and for the activation of signal-induced transcription of Shh target genes. In developing telencephalons deficient for Brg, Shh target genes were derepressed, whereas Brg-deleted cerebellar granule neuron precursors failed to respond to Shh to increase their proliferation. The repressor function of Brg was mediated through Gli3 and both the repressor and activator functions of Brg appeared to be independent of its ATPase activity. Furthermore, Brg facilitates Gli coactivator histone deacetylase (HDAC) binding to the regulatory regions of Shh target genes, providing a possible mechanism for its positive role in Shh signaling. Our results thus reveal that a complex chromatin regulation mechanism underlies the precise transcription outcomes of Shh signaling and its diverse roles during development.

The multi-dimensional roles of astrocytes in ALS.

PubMed

Yamanaka, Koji; Komine, Okiru

2018-01-01

Despite significant progress in understanding the molecular and genetic aspects of amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease characterized by the progressive loss of motor neurons, the precise and comprehensive pathomechanisms remain largely unknown. In addition to motor neuron involvement, recent studies using cellular and animal models of ALS indicate that there is a complex interplay between motor neurons and neighboring non-neuronal cells, such as astrocytes, in non-cell autonomous neurodegeneration. Astrocytes are key homeostatic cells that play numerous supportive roles in maintaining the brain environment. In neurodegenerative diseases such as ALS, astrocytes change their shape and molecular expression patterns and are referred to as reactive or activated astrocytes. Reactive astrocytes in ALS lose their beneficial functions and gain detrimental roles. In addition, interactions between motor neurons and astrocytes are impaired in ALS. In this review, we summarize growing evidence that astrocytes are critically involved in the survival and demise of motor neurons through several key molecules and cascades in astrocytes in both sporadic and inherited ALS. These observations strongly suggest that astrocytes have multi-dimensional roles in disease and are a viable therapeutic target for ALS. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Atrial fibrillation and arterial hypertension: A common duet with dangerous consequences where the renin angiotensin-aldosterone system plays an important role.

PubMed

Seccia, Teresa Maria; Caroccia, Brasilina; Muiesan, Maria Lorenza; Rossi, Gian Paolo

2016-03-01

Atrial fibrillation (AF) represents the most common sustained cardiac arrhythmia, as it affects 1%-2% of the general population and up to 15% of people over 80 years. High blood pressure, due to its high prevalence in the general population, is by far the most common condition associated with AF, although a variety of diseases, including valvular, coronary heart and metabolic diseases, are held to create the substrate favouring AF. Due to the concomitance of these conditions, it is quite challenging to dissect the precise role of high blood pressure in triggering/causing AF. Hence, even though the intimate association between high blood pressure and AF has been known for decades, the underlying mechanisms remain partially unknown. Accumulating evidences point to a major role of the renin-angiotensin-aldosterone system in inducing cardiac inflammation and fibrosis, and therefore electric and structural atrial and ventricular remodelling, with changes in ions and cell junctions leading to AF development. These evidences are herein reviewed with a particular emphasis to the role of the renin-angiotensin-system aldosterone system. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

NearSense - Advances Towards a Silicon-Based Terahertz Near-Field Imaging Sensor for Ex Vivo Breast Tumour Identification

NASA Astrophysics Data System (ADS)

Mavarani, Laven; Hillger, Philipp; Bücher, Thomas; Grzyb, Janusz; Pfeiffer, Ullrich R.; Cassar, Quentin; Al-Ibadi, Amel; Zimmer, Thomas; Guillet, Jean-Paul; Mounaix, Patrick; MacGrogan, Gaëtan

2018-03-01

Breast Cancer is one of the most frequently diagnosed cancer diseases worldwide, and the most common invasive tumour for women. As with all cancers, early detection plays a major role in reducing the mortality and morbidity rate. Currently, most breast cancers are detected due to clinical symptoms, or by screening mammography. The limitations of these techniques have resulted in research of alternative methods for imaging and detecting breast cancer. Apart from this, it is essential to define precise tumour margins during breast-conserving surgeries to reduce the re-excision rate. This study presents the advances in the development of a silicon-based THz sub-wavelength imager usable in life science applications, especially for tumour margin identification.

Heavy Metals Resisting Gravity in White Dwarfs?

NASA Astrophysics Data System (ADS)

Rauch, T.; Gamrath, S.; Quinet, P.; Hoyer, D.; Werner, K.; Kruk, J. W.

2017-03-01

Spectral lines of heavy metals, identified in high-resolution ultraviolet spectra of the DO-type white dwarf RX J0503.9-2854 (RE 0503-289), allow precise abundance determinations of these species by means of advanced non-local thermodynamic equilibrium stellar-atmosphere models - provided that reliable atomic data is available. Such analyses of Zn (atomic number Z = 30), Ga (31), Ge (32), As (33), Mo (42), Kr (36), Zr (40), Xe (54), and Ba (56) have recently shown that, without exception, their abundances are unexpectedly strongly supersolar (up to about 5 dex). This is much higher than predicted by recent asymptotic giant branch nucleosynthesis calculations. Thus, the interplay of gravitational settling and radiative levitation may play an important role for their photospheric prominence.

Reviewing the regulatory barriers for nanomedicine: global questions and challenges.

PubMed

Bowman, Diana M; Gatof, Jake

2015-01-01

Nanomedicine will play an increasing role in prevention and treatment across the entire healthcare spectrum. However, their precise market size, economic value and areas of application remain unclear. This opacity, including the question of what constitutes nanomedicine matters, especially when considered alongside the key regulatory questions and concerns. This article begins by placing these key questions into context in relation to the current scientific state of the art, focusing particular attention on the human health and safety context. In exploring these central questions surrounding the regulation of nanomedicine, this perspective also explores existing and suggested frameworks that aim to deal with emerging technologies more generally. It then outlines priority areas for action and general conclusions specific to nanomedicine.

Gut microbiota derived metabolites in cardiovascular health and disease.

PubMed

Wang, Zeneng; Zhao, Yongzhong

2018-05-03

Trillions of microbes inhabit the human gut, not only providing nutrients and energy to the host from the ingested food, but also producing metabolic bioactive signaling molecules to maintain health and elicit disease, such as cardiovascular disease (CVD). CVD is the leading cause of mortality worldwide. In this review, we presented gut microbiota derived metabolites involved in cardiovascular health and disease, including trimethylamine-N-oxide (TMAO), uremic toxins, short chain fatty acids (SCFAs), phytoestrogens, anthocyanins, bile acids and lipopolysaccharide. These gut microbiota derived metabolites play critical roles in maintaining a healthy cardiovascular function, and if dysregulated, potentially causally linked to CVD. A better understanding of the function and dynamics of gut microbiota derived metabolites holds great promise toward mechanistic predicative CVD biomarker discoveries and precise interventions.

Mu2e Solenoid Field Mapping System Design

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

Feher, Sandor; DeLurgio, Patrick M.; Elementi, Luciano

The Mu2e experiment at Fermilab plans to search for charged-lepton flavor violation by looking for neutrino-less muon to electron conversion in the field of the nucleus. A complex solenoid system and precise knowledge of its magnetic field play a major role in the experimental approach Mu2e has chosen. It is essential to map the solenoid field up to 10 -4 accuracy. This article describes the design of the Field Mapping System Mu2e will use to measure the magnetic field. Two different mechanical mapper systems, a survey based position determination of the in-house calibrated 3D Hall probes, a motion control system,more » and a data acquisition and readout system are presented.« less

Mu2e Solenoid Field Mapping System Design

DOE PAGES

Feher, Sandor; DeLurgio, Patrick M.; Elementi, Luciano; ...

2018-01-11

The Mu2e experiment at Fermilab plans to search for charged-lepton flavor violation by looking for neutrino-less muon to electron conversion in the field of the nucleus. A complex solenoid system and precise knowledge of its magnetic field play a major role in the experimental approach Mu2e has chosen. It is essential to map the solenoid field up to 10 -4 accuracy. This article describes the design of the Field Mapping System Mu2e will use to measure the magnetic field. Two different mechanical mapper systems, a survey based position determination of the in-house calibrated 3D Hall probes, a motion control system,more » and a data acquisition and readout system are presented.« less

Accurate de novo design of hyperstable constrained peptides

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

Bhardwaj, Gaurav; Mulligan, Vikram Khipple; Bahl, Christopher D.

Covalently-crosslinked peptides present attractive opportunities for developing new therapeutics. Lying between small molecule and protein therapeutics in size, natural crosslinked peptides play critical roles in signaling, virulence and immunity. Engineering novel peptides with precise control over their three-dimensional structures is a significant challenge. Here we describe the development of computational methods for de novo design of conformationally-restricted peptides, and the use of these methods to design hyperstable disulfide-stabilized miniproteins, heterochiral peptides, and N-C cyclic peptides. Experimentally-determined X-ray and NMR structures for 12 of the designs are nearly identical to the computational models. The computational design methods and stable scaffolds providemore » the basis for a new generation of peptide-based drugs.« less

Regularization iteration imaging algorithm for electrical capacitance tomography

NASA Astrophysics Data System (ADS)

Tong, Guowei; Liu, Shi; Chen, Hongyan; Wang, Xueyao

2018-03-01

The image reconstruction method plays a crucial role in real-world applications of the electrical capacitance tomography technique. In this study, a new cost function that simultaneously considers the sparsity and low-rank properties of the imaging targets is proposed to improve the quality of the reconstruction images, in which the image reconstruction task is converted into an optimization problem. Within the framework of the split Bregman algorithm, an iterative scheme that splits a complicated optimization problem into several simpler sub-tasks is developed to solve the proposed cost function efficiently, in which the fast-iterative shrinkage thresholding algorithm is introduced to accelerate the convergence. Numerical experiment results verify the effectiveness of the proposed algorithm in improving the reconstruction precision and robustness.

Thermal Molding of Organic Thin-Film Transistor Arrays on Curved Surfaces.

PubMed

Sakai, Masatoshi; Watanabe, Kento; Ishimine, Hiroto; Okada, Yugo; Yamauchi, Hiroshi; Sadamitsu, Yuichi; Kudo, Kazuhiro

2017-12-01

In this work, a thermal molding technique is proposed for the fabrication of plastic electronics on curved surfaces, enabling the preparation of plastic films with freely designed shapes. The induced strain distribution observed in poly(ethylene naphthalate) films when planar sheets were deformed into hemispherical surfaces clearly indicated that natural thermal contraction played an important role in the formation of the curved surface. A fingertip-shaped organic thin-film transistor array molded from a real human finger was fabricated, and slight deformation induced by touching an object was detected from the drain current response. This type of device will lead to the development of robot fingers equipped with a sensitive tactile sense for precision work such as palpation or surgery.

Bubbling and on-off intermittency in bailout embeddings.

PubMed

Cartwright, Julyan H E; Magnasco, Marcelo O; Piro, Oreste; Tuval, Idan

2003-07-01

We establish and investigate the conceptual connection between the dynamics of the bailout embedding of a Hamiltonian system and the dynamical regimes associated with the occurrence of bubbling and blowout bifurcations. The roles of the invariant manifold and the dynamics restricted to it, required in bubbling and blowout bifurcating systems, are played in the bailout embedding by the embedded Hamiltonian dynamical system. The Hamiltonian nature of the dynamics is precisely the distinctive feature of this instance of a bubbling or blowout bifurcation. The detachment of the embedding trajectories from the original ones can thus be thought of as transient on-off intermittency, and noise-induced avoidance of some regions of the embedded phase space can be recognized as Hamiltonian bubbling.

Determination of Martian Northern Polar Insolation Levels Using a Geodetic Elevation Model

NASA Technical Reports Server (NTRS)

Arrell, J. R.; Zuber, M. T.

2000-01-01

Solar insolation levels at the Martian polar caps bear significantly on the seasonal and climatic cycling of volatiles on that planet. In the northern hemisphere, the Martian surface slopes downhill from the equator to the pole such that the north polar cap is situated in a 5-km-deep hemispheric-scale depression. This large-scale topographic setting plays an important role in the insolation of the northern polar cap. Elevations measured by the Mars Orbiter Laser Altimeter (MOLA) provide comprehensive, high-accuracy topographical information required to precisely determine polar insolation. In this study, we employ a geodetic elevation model to quantify the north polar insolation and consider implications for seasonal and climatic changes. Additional information is contained in original extended abstract.

Towards optical control of single blood platelet activation

NASA Astrophysics Data System (ADS)

Spiryova, Darya V.; Karmatskih, Oleg Yu.; Vorob'ev, Alexei Yu.; Moskalensky, Alexander E.

2018-04-01

Blood platelets play a pivotal role in blood coagulation and in other normal and pathological processes. The understanding of fundamental mechanisms underlying their functions is very important for diagnostics and treatment. Single-cell experiments are needed for this purpose, which are complicated by insufficient spatiotemporal precision of conventional activation protocols. We present an approach to trigger single platelet activation optically, without the need of reagent mixing. This is achieved using photolabile compound, which rapidly delivers epinephrine upon UV irradiation. We demonstrated the applicability of the technique to rapidly induce platelet activation for studying dynamics of activation. The presented method may give novel fundamental knowledge about platelet functions and facilitate current research of their ability to deliver drugs to tumors or vascular injury sites.

Quantum speed limits in open system dynamics.

PubMed

del Campo, A; Egusquiza, I L; Plenio, M B; Huelga, S F

2013-02-01

Bounds to the speed of evolution of a quantum system are of fundamental interest in quantum metrology, quantum chemical dynamics, and quantum computation. We derive a time-energy uncertainty relation for open quantum systems undergoing a general, completely positive, and trace preserving evolution which provides a bound to the quantum speed limit. When the evolution is of the Lindblad form, the bound is analogous to the Mandelstam-Tamm relation which applies in the unitary case, with the role of the Hamiltonian being played by the adjoint of the generator of the dynamical semigroup. The utility of the new bound is exemplified in different scenarios, ranging from the estimation of the passage time to the determination of precision limits for quantum metrology in the presence of dephasing noise.

Foods and risk of bladder cancer: a case-control study in Uruguay.

PubMed

Balbi, J C; Larrinaga, M T; De Stefani, E; Mendilaharsu, M; Ronco, A L; Boffetta, P; Brennan, P

2001-10-01

A case-control study on 144 cases of transitional cell bladder carcinoma and 576 hospitalized controls was conducted in Montevideo, Uruguay. Barbecued meat, salted meat and fried eggs were associated with significant increased risks of bladder cancer (odds ratio (OR) for high intake of salted meat 4.04, 95% confidence interval (CI) 2.24-7.27). On the other hand, all fruits, cooked vegetables, potatoes and cheese were associated with inverse associations (OR for high consumption of potatoes 0.38, 95% CI 0.23-0.64). The associations with salted and barbecued meat suggest that the way of preserving or cooking meat play a role in bladder carcinogenesis. More precisely, N-nitroso compounds and heterocyclic amines could be involved in this process.

Meson Form Factors and Deep Exclusive Meson Production Experiments

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

Horn, Tanja

Pion and kaon electroproduction data play a unique role in Nature and our understanding of them is essential for explaining hadron structure. Precision longitudinaltransverse separated pion and kaon cross sections are of particular interest. They allow for the extraction of meson form factors and validation of understanding of hard exclusive and semi-inclusive reactions (π+, K+, π0, γ) towards 3D hadron imaging and potential future flavor decomposition. We review recent data and present prospects for deep exclusive pion and kaon electroproduction at the 12 GeV Jefferson Lab including the prospects to use projected charged- and neutral pion data to further determinemore » the spin, charge-parity and flavor of GPDs, including the helicity-flip GPDs.« less

A novel jet-based nano-hydroxyapatite patterning technique for osteoblast guidance

PubMed Central

Li, Xiang; Koller, Garrit; Huang, Jie; Di Silvio, Lucy; Renton, Tara; Esat, Minoo; Bonfield, William; Edirisinghe, Mohan

2010-01-01

Surface topography is well known to play a crucial role in influencing cellular responses to an implant material and is therefore important in bone tissue regeneration. A novel jet-based patterning technique, template-assisted electrohydrodynamic atomization spraying, was recently devised to control precisely the surface structure as well as its dimensions. In the present study, a detailed investigation of this patterning process was carried out. A range of nano-hydroxyapatite (nHA) line-shaped patterns <20 µm in width were successfully deposited on a commercially pure Ti surface by controlling the flow of an nHA suspension in an electric field. In vitro studies showed that the nHA patterns generated are capable of regulating the human osteoblast cell attachment and orientation. PMID:19493897

Heavy Metals Resisting Gravity in White Dwarfs?

NASA Technical Reports Server (NTRS)

Rauch, Thomas; Gamrath, Sebastien; Quinet, Pascal; Hoyer, Denny; Werner, Klaus; Kruk, Jeffrey Walter

2017-01-01

Spectral lines of heavy metals, identified in high-resolution ultraviolet spectra of the DO-type white dwarf RX J0503.9-2854 (RE 0503-289), allow precise abundance determinations of these species by means of advanced non-local thermo-dynamic equilibrium stellar-atmosphere models provided that reliable atomic data is available. Such analyses of Zn (atomic number Z equals 30), Ga (31), Ge (32), As (33), Mo(42), Kr (36), Zr (40), Xe (54), and Ba (56) have recently shown that, without exception, their abundances are unexpectedly strongly supersolar (up to about 5 dex (decimal exponent)). This is much higher than predicted by recent asymptotic giant branch nucleosynthesis calculations. Thus, the interplay of gravitational settling and radiative levitation may play an important role for their photospheric prominence.

Reaching to a featured formula to deduce the energy of the heaviest particles producing from the controlled thermonuclear fusion reactions

NASA Astrophysics Data System (ADS)

Majeed, Raad H.; Oudah, Osamah N.

2018-05-01

Thermonuclear fusion reaction plays an important role in developing and construction any power plant system. Studying the physical behavior for the possible mechanism governed energies released by the fusion products to precise understanding the related kinematics. In this work a theoretical formula controlled the general applied thermonuclear fusion reactions is achieved to calculating the fusion products energy depending upon the reactants physical properties and therefore, one can calculate other parameters governed a given reaction. By using this formula, the energy spectrum of 4He produced from T-3He fusion reaction has been sketched with respect to reaction angle and incident energy ranged from (0.08-0.6) MeV.

Understanding subcellular function on the nanometer scale in real time: Single-molecule imaging in living bacteria

NASA Astrophysics Data System (ADS)

Biteen, Julie

It has long been recognized that microorganisms play a central role in our lives. By beating the diffraction limit that restricts traditional light microscopy, single-molecule fluorescence imaging is a precise, noninvasive way to sensitively probe position and dynamics, even in living cells. We are pioneering this super-resolution imaging method for unraveling important biological processes in live bacteria, and I will discuss how we infer function from subcellular dynamics (Tuson and Biteen, Analytical Chemistry 2015). In particular, we have understood the mechanism of membrane-bound transcription regulation in the pathogenic Vibrio cholerae, revealed an intimate and dynamic coupling between DNA mismatch recognition and DNA replication, and measured starch utilization in an important member of the human gut microbiome.

The Chandra Strong Lens Sample: Revealing Baryonic Physics In Strong Lensing Selected Clusters

NASA Astrophysics Data System (ADS)

Bayliss, Matthew

2017-08-01

We propose for Chandra imaging of the hot intra-cluster gas in a unique new sample of 29 galaxy clusters selected purely on their strong gravitational lensing signatures. This will be the first program targeting a purely strong lensing selected cluster sample, enabling new comparisons between the ICM properties and scaling relations of strong lensing and mass/ICM selected cluster samples. Chandra imaging, combined with high precision strong lens models, ensures powerful constraints on the distribution and state of matter in the cluster cores. This represents a novel angle from which we can address the role played by baryonic physics |*| the infamous |*|gastrophysics|*| in shaping the cores of massive clusters, and opens up an exciting new galaxy cluster discovery space with Chandra.

The Chandra Strong Lens Sample: Revealing Baryonic Physics In Strong Lensing Selected Clusters

NASA Astrophysics Data System (ADS)

Bayliss, Matthew

2017-09-01

We propose for Chandra imaging of the hot intra-cluster gas in a unique new sample of 29 galaxy clusters selected purely on their strong gravitational lensing signatures. This will be the first program targeting a purely strong lensing selected cluster sample, enabling new comparisons between the ICM properties and scaling relations of strong lensing and mass/ICM selected cluster samples. Chandra imaging, combined with high precision strong lens models, ensures powerful constraints on the distribution and state of matter in the cluster cores. This represents a novel angle from which we can address the role played by baryonic physics -- the infamous ``gastrophysics''-- in shaping the cores of massive clusters, and opens up an exciting new galaxy cluster discovery space with Chandra.

[Methods for determination of cholinesterase activity].

PubMed

Dingová, D; Hrabovská, A

2015-01-01

Cholinesterases hydrolyze acetylcholine and thus they play a key role in a process of cholinergic neurotransmission. Changes in their activities are linked to many diseases (e.g Alzheimer disease, Parkinson disease, lipid disorders). Thus, it is important to determine their activity in a fast, simply and precise way. In this review, different approaches of studying cholinesterase activities (e.g pH-dependent, spectrophotometric, radiometric, histochemical methods or biosensors) are discussed. Comparisons, advantages or disadvantages of selected methods (e.g most widely used Ellman's assay, extremely sensitive Johnson Russell method or modern technique with golden nanoparticles) are presented. This review enables one to choose a suitable method for determination of cholinesterase activities with respect to laboratory equipment, type of analysis, pH, temperature scale or special conditions.

Thermal Molding of Organic Thin-Film Transistor Arrays on Curved Surfaces

NASA Astrophysics Data System (ADS)

Sakai, Masatoshi; Watanabe, Kento; Ishimine, Hiroto; Okada, Yugo; Yamauchi, Hiroshi; Sadamitsu, Yuichi; Kudo, Kazuhiro

2017-05-01

In this work, a thermal molding technique is proposed for the fabrication of plastic electronics on curved surfaces, enabling the preparation of plastic films with freely designed shapes. The induced strain distribution observed in poly(ethylene naphthalate) films when planar sheets were deformed into hemispherical surfaces clearly indicated that natural thermal contraction played an important role in the formation of the curved surface. A fingertip-shaped organic thin-film transistor array molded from a real human finger was fabricated, and slight deformation induced by touching an object was detected from the drain current response. This type of device will lead to the development of robot fingers equipped with a sensitive tactile sense for precision work such as palpation or surgery.

[Early decentralization of health services in Argentina: the construction of the health system in Córdoba, 1930-1955].

PubMed

Ortiz Bergia, María José

2015-01-01

This paper analyzes the process of construction of the Argentine public health system, highlighting the limitations that occurred in the proposed nationalization of health policy in the postwar period and the central role played by subnational jurisdictions, making the provision of services rendered on a provincial basis. More precisely, in this respect it is seen how the expansion of health services in some provinces shows us how, in the second quarter of the twentieth century, it was primarily the result of the action of local rather than national departments. In order to better elucidate this process, the trajectory of public healthcare facilities in the province of Córdoba between 1930 and 1955 was studied.

Quantum interference and complex photon statistics in waveguide QED

NASA Astrophysics Data System (ADS)

Zhang, Xin H. H.; Baranger, Harold U.

2018-02-01

We obtain photon statistics by using a quantum jump approach tailored to a system in which one or two qubits are coupled to a one-dimensional waveguide. Photons confined in the waveguide have strong interference effects, which are shown to play a vital role in quantum jumps and photon statistics. For a single qubit, for instance, the bunching of transmitted photons is heralded by a jump that increases the qubit population. We show that the distribution and correlations of waiting times offer a clearer and more precise characterization of photon bunching and antibunching. Further, the waiting times can be used to characterize complex correlations of photons which are hidden in g(2 )(τ ) , such as a mixture of bunching and antibunching.

Radiative neutrino mass and Majorana dark matter within an inert Higgs doublet model

NASA Astrophysics Data System (ADS)

Ahriche, Amine; Jueid, Adil; Nasri, Salah

2018-05-01

We consider an extension of the standard model (SM) with an inert Higgs doublet and three Majorana singlet fermions to address both origin and the smallness of neutrino masses and dark matter (DM) problems. In this setup, the lightest Majorana singlet fermion plays the role of DM candidate and the model parameter space can be accommodated to avoid different experimental constraints such as lepton flavor violating processes and electroweak precision tests. The neutrino mass is generated at one-loop level a la Scotogenic model and its smallness is ensured by the degeneracy between the C P -odd and C P -even scalar members of the inert doublet. Interesting signatures at both leptonic and hadronic colliders are discussed.

The role of precise time in IFF

NASA Technical Reports Server (NTRS)

Bridge, W. M.

1982-01-01

The application of precise time to the identification of friend or foe (IFF) problem is discussed. The simple concept of knowing when to expect each signal is exploited in a variety of ways to achieve an IFF system which is hard to detect, minimally exploitable and difficult to jam. Precise clocks are the backbone of the concept and the various candidates for this role are discussed. The compact rubidium-controlled oscillator is the only practical candidate.

Redefinition of rubisco carboxylase reaction reveals origin of water for hydration and new roles for active-site residues.

PubMed

Kannappan, Babu; Gready, Jill E

2008-11-12

Crystallographic, mutagenesis, kinetic, and computational studies on Rubisco over three decades have revealed much about its catalytic mechanism and the role played by several active-site residues. However, key questions remain unanswered. Specific details of the carboxylase and oxygenase mechanisms, required to underpin the rational re-engineering of Rubisco, are still speculative. Here we address critical gaps in knowledge with a definitive comprehensive computational investigation of the mechanism of carboxylase activity at the Rubisco active site. Density functional theory calculations (B3LYP/6-31G(d,p)) were performed on active-site fragment models of a size up to 77 atoms, not previously possible computationally. All amino acid residues suspected to play roles in the acid-base chemistry in the multistep reaction, and interacting directly with the central Mg (2+) atom and the reactive moiety of substrate and intermediates, were included. The results provide a firm basis for us to propose a novel mechanism for the entire sequence of reactions in the carboxylase catalysis and to define precise roles for the active-site residues, singly and in concert. In this mechanism, the carbamylated LYS201 plays a more limited role than previously proposed but is crucial for initiating the reaction by acting as a base in the enolization. We suggest a wider role for HIS294, with involvement in the carboxylation, hydration, and C2-C3 bond-scission steps, consistent with the suggestion of Harpel et al. (1998) but contrary to the consensus view of Cleland et al. (1998). In contrast to the common assumption that the water molecule for the hydration step comes from within the active site, we propose that the Mg-coordinated water is not dissociated at the start of the gas-addition reaction but rather remains coordinated and is used for the hydration of the C3 carbon atom. New roles are also proposed for LYS175, GLU204, and HIS294. The mechanism suggests roles in the gas-addition step for residues in three spatially distinct regions of the active site, HIS294 and LYS334 in the C-terminal domain of the large subunit (LSU), but also hitherto unsuspected roles for a cluster of three residues (ASN123, GLU60, and TYR20) in the N-terminal domain of the partner LSU of the dimer containing the active site. Our new mechanism is supported by existing experimental data, provides new convincing interpretations of previously puzzling data, and allows new insights into mutational strategies for improving Rubisco activity.

Clinical implications of the reduced activity of the GH-IGF-I axis in older men.

PubMed

Ceda, G P; Dall'Aglio, E; Maggio, M; Lauretani, F; Bandinelli, S; Falzoi, C; Grimaldi, W; Ceresini, G; Corradi, F; Ferrucci, L; Valenti, G; Hoffman, A R

2005-01-01

During the last decade, a significant body of evidence has accumulated, indicating that IGF-I might play a role in several pathological conditions commonly seen during aging, such as atherosclerosis and cardiovascular disease (CVD), cognitive decline, dementia, sarcopenia and frailty. A vascular protective role for IGF-I has been suggested because of its ability to stimulate nitric oxide production from endothelial and vascular smooth muscle cells. In cross sectional studies, low IGF-I levels have been associated with unfavorable CVD risk factors profile, such as atherosclerosis, abnormal lipoprotein levels and hypertension, while in prospective studies, lower IGF-I levels predict future development of ischemic heart disease. The fall in IGF-I levels with aging correlates with cognitive decline and it has been suggested that IGF-I plays a role in the development of dementia. IGF-I is highly expressed within the brain and is essential for normal brain development. IGF-I has anti-apoptotic and neuroprotective effects and promotes projection neuron growth, dendritic arborization and synaptogenesis. Collectively, these data are consistent with a causal link between the age-related decline in GH and IGF-I levels and cognitive deficits in older persons. Finally, there is evidence of a relationship between declining GH and IGF-I levels and age-related changes in body composition and physical function. However, few studies have documented a precise role of IGF-I in the development of sarcopenia, frailty and poor mobility. We have recently documented that serum IGF-I is significantly associated with measures of muscle strength and physical performance in men and to a lesser extent in women. In conclusion, IGF-I is a pleiotropic hormone that in older persons may positively affect the cardiovascular system, the central nervous system and physical function.

Integration of role-playing into technical skills training: a randomized controlled trial.

PubMed

Nikendei, C; Kraus, B; Schrauth, M; Weyrich, P; Zipfel, S; Herzog, W; Jünger, J

2007-11-01

Recently, efforts have been undertaken to enhance the face validity of technical skills training by introducing role-plays and standardised patients. Since little is known about the effects of role-playing with respect to the realism of a training situation and students' objective performance, we performed a randomized controlled trial. 36 medical students participated in videotaped small group skills-lab sessions on the topics of Doppler sonography and gastric tube insertion. One half of the students participated in role-plays and the other half practised without role-playing. Realism of the training situation was analysed by means of post-intervention self-selected student survey evaluations. Technical performance and patient-physician communication were assessed by independent ratings of the videotaped sessions. The physician's role was regarded to be significantly more realistic when performing role-plays. Assessment of videotaped sessions showed that practising technical skills by performing role-plays resulted in significantly better patient-physician communication whereas students' technical performance did not differ between groups. Introducing role-plays enhances the realism of technical skills training and leads to better patient-physician communication. Students do not seem to be overstrained by practising clinical technical skills using role-plays. We conclude that role-playing is a valuable method in practising technical skills.

The role of the faceguard in the production of flexion injuries to the cervical spine in football.

PubMed

Melvin, W J; Dunlop, H W; Hetherington, R F; Kerr, J W

1965-11-20

The precise role of the single-bar face mask in producing major flexion violence to the cervical spine has been studied by review of game movies, analysis of the radiographs and detailed interviews with two players who sustained fractures of cervical spine. The single-bar face mask can become fixed in the ground, thereby forcing a runner's head down onto his chest as the trunk moves forward. Preventive measures embodying modifications in the face mask, strict coaching in football techniques and the institution of safety factors in the playing rules are proposed. Appreciation of the mechanism of injury is urged in order to encourage careful inspection of protective head gear as well as to direct the attention of team physicians to the possibility of serious flexion injury to the cervical spine occurring without dramatic evidence. This report is not a plea for abandonment of the face mask but rather a suggestion for careful selection of a safe and efficient mask.

RecA binding to a single double-stranded DNA molecule: A possible role of DNA conformational fluctuations

PubMed Central

Leger, J. F.; Robert, J.; Bourdieu, L.; Chatenay, D.; Marko, J. F.

1998-01-01

Most genetic regulatory mechanisms involve protein–DNA interactions. In these processes, the classical Watson–Crick DNA structure sometimes is distorted severely, which in turn enables the precise recognition of the specific sites by the protein. Despite its key importance, very little is known about such deformation processes. To address this general question, we have studied a model system, namely, RecA binding to double-stranded DNA. Results from micromanipulation experiments indicate that RecA binds strongly to stretched DNA; based on this observation, we propose that spontaneous thermal stretching fluctuations may play a role in the binding of RecA to DNA. This has fundamental implications for the protein–DNA binding mechanism, which must therefore rely in part on a combination of flexibility and thermal fluctuations of the DNA structure. We also show that this mechanism is sequence sensitive. Theoretical simulations support this interpretation of our experimental results, and it is argued that this is of broad relevance to DNA–protein interactions. PMID:9770480

Crystal structure of the epithelial calcium channel TRPV6.

PubMed

Saotome, Kei; Singh, Appu K; Yelshanskaya, Maria V; Sobolevsky, Alexander I

2016-06-23

Precise regulation of calcium homeostasis is essential for many physiological functions. The Ca(2+)-selective transient receptor potential (TRP) channels TRPV5 and TRPV6 play vital roles in calcium homeostasis as Ca(2+) uptake channels in epithelial tissues. Detailed structural bases for their assembly and Ca(2+) permeation remain obscure. Here we report the crystal structure of rat TRPV6 at 3.25 Å resolution. The overall architecture of TRPV6 reveals shared and unique features compared with other TRP channels. Intracellular domains engage in extensive interactions to form an intracellular 'skirt' involved in allosteric modulation. In the K(+) channel-like transmembrane domain, Ca(2+) selectivity is determined by direct coordination of Ca(2+) by a ring of aspartate side chains in the selectivity filter. On the basis of crystallographically identified cation-binding sites at the pore axis and extracellular vestibule, we propose a Ca(2+) permeation mechanism. Our results provide a structural foundation for understanding the regulation of epithelial Ca(2+) uptake and its role in pathophysiology.

Ventromedial prefrontal cortex mediates visual attention during facial emotion recognition.

PubMed

Wolf, Richard C; Philippi, Carissa L; Motzkin, Julian C; Baskaya, Mustafa K; Koenigs, Michael

2014-06-01

The ventromedial prefrontal cortex is known to play a crucial role in regulating human social and emotional behaviour, yet the precise mechanisms by which it subserves this broad function remain unclear. Whereas previous neuropsychological studies have largely focused on the role of the ventromedial prefrontal cortex in higher-order deliberative processes related to valuation and decision-making, here we test whether ventromedial prefrontal cortex may also be critical for more basic aspects of orienting attention to socially and emotionally meaningful stimuli. Using eye tracking during a test of facial emotion recognition in a sample of lesion patients, we show that bilateral ventromedial prefrontal cortex damage impairs visual attention to the eye regions of faces, particularly for fearful faces. This finding demonstrates a heretofore unrecognized function of the ventromedial prefrontal cortex-the basic attentional process of controlling eye movements to faces expressing emotion. © The Author (2014). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Emerging Treatments in Eating Disorders.

PubMed

Lutter, Michael

2017-07-01

Eating disorders (EDs), including anorexia nervosa, bulimia nervosa, and binge-eating disorder, constitute a class of common and deadly psychiatric disorders. While numerous studies in humans highlight the important role of neurobiological alterations in the development of ED-related behaviors, the precise neural substrate that mediates this risk is unknown. Historically, pharmacological interventions have played a limited role in the treatment of eating disorders, typically providing symptomatic relief of comorbid psychiatric issues, like depression and anxiety, in support of the standard nutritional and psychological treatments. To date there are no Food and Drug Administration-approved medications or procedures for anorexia nervosa, and only one Food and Drug Administration-approved medication each for bulimia nervosa (fluoxetine) and binge-eating disorder (lisdexamfetamine). While there is little primary interest in drug development for eating disorders, postmarket monitoring of medications and procedures approved for other indications has identified several novel treatment options for patients with eating disorders. In this review, I utilize searches of the PubMed and ClinicalTrials.gov databases to highlight emerging treatments in eating disorders.

Loss of Pancreas upon Activated Wnt Signaling Is Concomitant with Emergence of Gastrointestinal Identity

PubMed Central

Herrero-Martin, Griselda; Puri, Sapna; Taketo, Makoto Mark; Rojas, Anabel; Hebrok, Matthias; Cano, David A.

2016-01-01

Organ formation is achieved through the complex interplay between signaling pathways and transcriptional cascades. The canonical Wnt signaling pathway plays multiple roles during embryonic development including patterning, proliferation and differentiation in distinct tissues. Previous studies have established the importance of this pathway at multiple stages of pancreas formation as well as in postnatal organ function and homeostasis. In mice, gain-of-function experiments have demonstrated that activation of the canonical Wnt pathway results in pancreatic hypoplasia, a phenomenon whose underlying mechanisms remains to be elucidated. Here, we show that ectopic activation of epithelial canonical Wnt signaling causes aberrant induction of gastric and intestinal markers both in the pancreatic epithelium and mesenchyme, leading to the development of gut-like features. Furthermore, we provide evidence that β -catenin-induced impairment of pancreas formation depends on Hedgehog signaling. Together, our data emphasize the developmental plasticity of pancreatic progenitors and further underscore the key role of precise regulation of signaling pathways to maintain appropriate organ boundaries. PMID:27736991

Three-dimensional patterning in biomedicine: Importance and applications in neuropharmacology.

PubMed

Vikram Singh, Ajay; Gharat, Tanmay; Batuwangala, Madu; Park, Byung-Wook; Endlein, Thomas; Sitti, Metin

2018-04-01

Nature manufactures biological systems in three dimensions with precisely controlled spatiotemporal profiles on hierarchical length and time scales. In this article, we review 3D patterning of biological systems on synthetic platforms for neuropharmacological applications. We briefly describe 3D versus 2D chemical and topographical patterning methods and their limitations. Subsequently, an overview of introducing a third dimension in neuropharmacological research with delineation of chemical and topographical roles is presented. Finally, toward the end of this article, an explanation of how 3D patterning has played a pivotal role in relevant fields of neuropharmacology to understand neurophysiology during development, normal health, and disease conditions is described. The future prospects of organs-on-a--like devices to mimic patterned blood-brain barrier in the context of neurotherapeutic discovery and development for the prioritization of lead candidates, membrane potential, and toxicity testing are also described. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1369-1382, 2018. © 2017 Wiley Periodicals, Inc.

Generation of Well-Defined Micro/Nanoparticles via Advanced Manufacturing Techniques for Therapeutic Delivery

PubMed Central

Zhang, Peipei; Xia, Junfei; Luo, Sida

2018-01-01

Micro/nanoparticles have great potentials in biomedical applications, especially for drug delivery. Existing studies identified that major micro/nanoparticle features including size, shape, surface property and component materials play vital roles in their in vitro and in vivo applications. However, a demanding challenge is that most conventional particle synthesis techniques such as emulsion can only generate micro/nanoparticles with a very limited number of shapes (i.e., spherical or rod shapes) and have very loose control in terms of particle sizes. We reviewed the advanced manufacturing techniques for producing micro/nanoparticles with precisely defined characteristics, emphasizing the use of these well-controlled micro/nanoparticles for drug delivery applications. Additionally, to illustrate the vital roles of particle features in therapeutic delivery, we also discussed how the above-mentioned micro/nanoparticle features impact in vitro and in vivo applications. Through this review, we highlighted the unique opportunities in generating controllable particles via advanced manufacturing techniques and the great potential of using these micro/nanoparticles for therapeutic delivery. PMID:29670013

Illuminating the multifaceted roles of neurotransmission in shaping neuronal circuitry.

PubMed

Okawa, Haruhisa; Hoon, Mrinalini; Yoshimatsu, Takeshi; Della Santina, Luca; Wong, Rachel O L

2014-09-17

Across the nervous system, neurons form highly stereotypic patterns of synaptic connections that are designed to serve specific functions. Mature wiring patterns are often attained upon the refinement of early, less precise connectivity. Much work has led to the prevailing view that many developing circuits are sculpted by activity-dependent competition among converging afferents, which results in the elimination of unwanted synapses and the maintenance and strengthening of desired connections. Studies of the vertebrate retina, however, have recently revealed that activity can play a role in shaping developing circuits without engaging competition among converging inputs that differ in their activity levels. Such neurotransmission-mediated processes can produce stereotypic wiring patterns by promoting selective synapse formation rather than elimination. We discuss how the influence of transmission may also be limited by circuit design and further highlight the importance of transmission beyond development in maintaining wiring specificity and synaptic organization of neural circuits. Copyright © 2014 Elsevier Inc. All rights reserved.

Charged residues in the H-NS linker drive DNA binding and gene silencing in single cells.

PubMed

Gao, Yunfeng; Foo, Yong Hwee; Winardhi, Ricksen S; Tang, Qingnan; Yan, Jie; Kenney, Linda J

2017-11-21

Nucleoid-associated proteins (NAPs) facilitate chromosome organization in bacteria, but the precise mechanism remains elusive. H-NS is a NAP that also plays a major role in silencing pathogen genes. We used genetics, single-particle tracking in live cells, superresolution microscopy, atomic force microscopy, and molecular dynamics simulations to examine H-NS/DNA interactions in single cells. We discovered a role for the unstructured linker region connecting the N-terminal oligomerization and C-terminal DNA binding domains. In the present work we demonstrate that linker amino acids promote engagement with DNA. In the absence of linker contacts, H-NS binding is significantly reduced, although no change in chromosome compaction is observed. H-NS is not localized to two distinct foci; rather, it is scattered all around the nucleoid. The linker makes DNA contacts that are required for gene silencing, while chromosome compaction does not appear to be an important H-NS function.

The influence of chronotype on making music: circadian fluctuations in pianists' fine motor skills

PubMed Central

Van Vugt, Floris T.; Treutler, Katharina; Altenmüller, Eckart; Jabusch, Hans-Christian

2013-01-01

Making music on a professional level requires a maximum of sensorimotor precision. Chronotype-dependent fluctuations of sensorimotor precision in the course of the day may prove a challenge for musicians because public performances or recordings are usually scheduled at fixed times of the day. We investigated pianists' sensorimotor timing precision in a scale playing task performed in the morning and in the evening. Participants' chronotype was established through the Munich Chrono-Type Questionnaire, where mid-sleep time served as a marker for the individual chronotypes. Twenty-one piano students were included in the study. Timing precision was decomposed into consistent within-trial variability (irregularity) and residual, between-trial variability (instability). The timing patterns of late chronotype pianists were more stable in the evening than in the morning, whereas early chronotype pianists did not show a difference between the two recording timepoints. In sum, the present results indicate that even highly complex sensorimotor tasks such as music playing are affected by interactions between chronotype and the time of day. Thus, even long-term, massed practice of these expert musicians has not been able to wash out circadian fluctuations in performance. PMID:23847515

The influence of chronotype on making music: circadian fluctuations in pianists' fine motor skills.

PubMed

Van Vugt, Floris T; Treutler, Katharina; Altenmüller, Eckart; Jabusch, Hans-Christian

2013-01-01

Making music on a professional level requires a maximum of sensorimotor precision. Chronotype-dependent fluctuations of sensorimotor precision in the course of the day may prove a challenge for musicians because public performances or recordings are usually scheduled at fixed times of the day. We investigated pianists' sensorimotor timing precision in a scale playing task performed in the morning and in the evening. Participants' chronotype was established through the Munich Chrono-Type Questionnaire, where mid-sleep time served as a marker for the individual chronotypes. Twenty-one piano students were included in the study. Timing precision was decomposed into consistent within-trial variability (irregularity) and residual, between-trial variability (instability). The timing patterns of late chronotype pianists were more stable in the evening than in the morning, whereas early chronotype pianists did not show a difference between the two recording timepoints. In sum, the present results indicate that even highly complex sensorimotor tasks such as music playing are affected by interactions between chronotype and the time of day. Thus, even long-term, massed practice of these expert musicians has not been able to wash out circadian fluctuations in performance.

Precision phase estimation based on weak-value amplification

NASA Astrophysics Data System (ADS)

Qiu, Xiaodong; Xie, Linguo; Liu, Xiong; Luo, Lan; Li, Zhaoxue; Zhang, Zhiyou; Du, Jinglei

2017-02-01

In this letter, we propose a precision method for phase estimation based on the weak-value amplification (WVA) technique using a monochromatic light source. The anomalous WVA significantly suppresses the technical noise with respect to the intensity difference signal induced by the phase delay when the post-selection procedure comes into play. The phase measured precision of this method is proportional to the weak-value of a polarization operator in the experimental range. Our results compete well with the wide spectrum light phase weak measurements and outperform the standard homodyne phase detection technique.

Using Online Role-Play to Promote Collaborative Argument and Collective Action

ERIC Educational Resources Information Center

Doerr-Stevens, Candance; Beach, Richard; Boeser, Elizabeth

2011-01-01

This article discusses how students use online role-play to collaborate and change real school policy. Playing different characters in an online role-play, students explore controversial aspects of Internet filtering and adopt a plan to change their school's policy. Through engaging in collaborative argumentation during their role-play, students…

Non-essential role for cilia in coordinating precise alignment of lens fibres

PubMed Central

Sugiyama, Yuki; Shelley, Elizabeth J.; Yoder, Bradley K.; Kozmik, Zbynek; May-Simera, Helen L.; Beales, Philip L.; Lovicu, Frank J.; McAvoy, John W.

2016-01-01

The primary cilium, a microtubule-based organelle found in most cells, is a centre for mechano-sensing fluid movement and cellular signalling, notably through the Hedgehog pathway. We recently found that each lens fibre cell has an apically situated primary cilium that is polarised to the side of the cell facing the anterior pole of the lens. The direction of polarity is similar in neighbouring cells so that in the global view, lens fibres exhibit planar cell polarity (PCP) along the equatorial-anterior polar axis. Ciliogenesis has been associated with the establishment of PCP, although the exact relationship between PCP and the role of cilia is still controversial. To test the hypothesis that the primary cilia have a role in coordinating the precise alignment/orientation of the fibre cells, IFT88, a key component of the intraflagellar transport (IFT) complex, was removed specifically from the lens at different developmental stages using several lens-specific Cre-expressing mouse lines (MLR10- and LR-Cre). Irrespective of which Cre-line was adopted, both demonstrated that in IFT88-depleted cells, the ciliary axoneme was absent or substantially shortened, confirming the disruption of primary cilia formation. However no obvious histological defects were detected even when IFT88 was removed from the lens placode as early as E9.5. Specifically, the lens fibres aligned/oriented towards the poles to form the characteristic Y-shaped sutures as normal. Consistent with this, in primary lens epithelial explants prepared from these conditional knockout mouse lenses, the basal bodies still showed polarised localisation at the apical surface of elongating cells upon FGF-induced fibre differentiation. We further investigated the lens phenotype in knockouts of Bardet–Biedl Syndrome (BBS) proteins 4 and 8, the components of the BBSome complex which modulate ciliary function. In these BBS4 and 8 knockout lenses, again we found the pattern of the anterior sutures formed by the apical tips of elongating/migrating fibres were comparable to the control lenses. Taken together, these results indicate that primary cilia do not play an essential role in the precise cellular alignment/orientation of fibre cells. Thus, it appears that in the lens cilia are not required to establish PCP. PMID:26825015

Precision Nutrition and Omega-3 Polyunsaturated Fatty Acids: A Case for Personalized Supplementation Approaches for the Prevention and Management of Human Diseases

PubMed Central

Chilton, Floyd H.; Dutta, Rahul; Reynolds, Lindsay M.; Sergeant, Susan; Mathias, Rasika A.; Seeds, Michael C.

2017-01-01

Background: Dietary essential omega-6 (n-6) and omega-3 (n-3) 18 carbon (18C-) polyunsaturated fatty acids (PUFA), linoleic acid (LA) and α-linolenic acid (ALA), can be converted (utilizing desaturase and elongase enzymes encoded by FADS and ELOVL genes) to biologically-active long chain (LC; >20)-PUFAs by numerous cells and tissues. These n-6 and n-3 LC-PUFAs and their metabolites (ex, eicosanoids and endocannabinoids) play critical signaling and structural roles in almost all physiologic and pathophysiologic processes. Methods: This review summarizes: (1) the biosynthesis, metabolism and roles of LC-PUFAs; (2) the potential impact of rapidly altering the intake of dietary LA and ALA; (3) the genetics and evolution of LC-PUFA biosynthesis; (4) Gene–diet interactions that may lead to excess levels of n-6 LC-PUFAs and deficiencies of n-3 LC-PUFAs; and (5) opportunities for precision nutrition approaches to personalize n-3 LC-PUFA supplementation for individuals and populations. Conclusions: The rapid nature of transitions in 18C-PUFA exposure together with the genetic variation in the LC-PUFA biosynthetic pathway found in different populations make mal-adaptations a likely outcome of our current nutritional environment. Understanding this genetic variation in the context of 18C-PUFA dietary exposure should enable the development of individualized n-3 LC-PUFA supplementation regimens to prevent and manage human disease. PMID:29068398

How Nectar-Feeding Bats Localize their Food: Echolocation Behavior of Leptonycteris yerbabuenae Approaching Cactus Flowers

PubMed Central

Koblitz, Jens C.; Fleming, Theodore H.; Medellín, Rodrigo A.; Kalko, Elisabeth K. V.; Schnitzler, Hans-Ulrich; Tschapka, Marco

2016-01-01

Nectar-feeding bats show morphological, physiological, and behavioral adaptations for feeding on nectar. How they find and localize flowers is still poorly understood. While scent cues alone allow no precise localization of a floral target, the spatial properties of flower echoes are very precise and could play a major role, particularly at close range. The aim of this study is to understand the role of echolocation for classification and localization of flowers. We compared the approach behavior of Leptonycteris yerbabuenae to flowers of a columnar cactus, Pachycereus pringlei, to that to an acrylic hollow hemisphere that is acoustically conspicuous to bats, but has different acoustic properties and, contrary to the cactus flower, present no scent. For recording the flight and echolocation behaviour we used two infrared video cameras under stroboscopic illumination synchronized with ultrasound recordings. During search flights all individuals identified both targets as a possible food source and initiated an approach flight; however, they visited only the cactus flower. In experiments with the acrylic hemisphere bats aborted the approach at ca. 40–50 cm. In the last instant before the flower visit the bats emitted a long terminal group of 10–20 calls. This is the first report of this behaviour for a nectar-feeding bat. Our findings suggest that L. yerbabuenae use echolocation for classification and localization of cactus flowers and that the echo-acoustic characteristics of the flower guide the bats directly to the flower opening. PMID:27684373

A Transient Expression of Prospero Promotes Cell Cycle Exit of Drosophila Postembryonic Neurons through the Regulation of Dacapo

PubMed Central

Colonques, Jordi; Ceron, Julian; Reichert, Heinrich; Tejedor, Francisco J.

2011-01-01

Cell proliferation, specification and terminal differentiation must be precisely coordinated during brain development to ensure the correct production of different neuronal populations. Most Drosophila neuroblasts (NBs) divide asymmetrically to generate a new NB and an intermediate progenitor called ganglion mother cell (GMC) which divides only once to generate two postmitotic cells called ganglion cells (GCs) that subsequently differentiate into neurons. During the asymmetric division of NBs, the homeodomain transcription factor PROSPERO is segregated into the GMC where it plays a key role as cell fate determinant. Previous work on embryonic neurogenesis has shown that PROSPERO is not expressed in postmitotic neuronal progeny. Thus, PROSPERO is thought to function in the GMC by repressing genes required for cell-cycle progression and activating genes involved in terminal differentiation. Here we focus on postembryonic neurogenesis and show that the expression of PROSPERO is transiently upregulated in the newly born neuronal progeny generated by most of the larval NBs of the OL and CB. Moreover, we provide evidence that this expression of PROSPERO in GCs inhibits their cell cycle progression by activating the expression of the cyclin-dependent kinase inhibitor (CKI) DACAPO. These findings imply that PROSPERO, in addition to its known role as cell fate determinant in GMCs, provides a transient signal to ensure a precise timing for cell cycle exit of prospective neurons, and hence may link the mechanisms that regulate neurogenesis and those that control cell cycle progression in postembryonic brain development. PMID:21552484

Differential effects of ADORA2A gene variations in pre-attentive visual sensory memory subprocesses.

PubMed

Beste, Christian; Stock, Ann-Kathrin; Ness, Vanessa; Epplen, Jörg T; Arning, Larissa

2012-08-01

The ADORA2A gene encodes the adenosine A(2A) receptor that is highly expressed in the striatum where it plays a role in modulating glutamatergic and dopaminergic transmission. Glutamatergic signaling has been suggested to play a pivotal role in cognitive functions related to the pre-attentive processing of external stimuli. Yet, the precise molecular mechanism of these processes is poorly understood. Therefore, we aimed to investigate whether ADORA2A gene variation has modulating effects on visual pre-attentive sensory memory processing. Studying two polymorphisms, rs5751876 and rs2298383, in 199 healthy control subjects who performed a partial-report paradigm, we find that ADORA2A variation is associated with differences in the efficiency of pre-attentive sensory memory sub-processes. We show that especially the initial visual availability of stimulus information is rendered more efficiently in the homozygous rare genotype groups. Processes related to the transfer of information into working memory and the duration of visual sensory (iconic) memory are compromised in the homozygous rare genotype groups. Our results show a differential genotype-dependent modulation of pre-attentive sensory memory sub-processes. Hence, we assume that this modulation may be due to differential effects of increased adenosine A(2A) receptor signaling on glutamatergic transmission and striatal medium spiny neuron (MSN) interaction. Copyright © 2011 Elsevier B.V. and ECNP. All rights reserved.

Modulation of Intestinal Paracellular Transport by Bacterial Pathogens.

PubMed

Roxas, Jennifer Lising; Viswanathan, V K

2018-03-25

The passive and regulated movement of ions, solutes, and water via spaces between cells of the epithelial monolayer plays a critical role in the normal intestinal functioning. This paracellular pathway displays a high level of structural and functional specialization, with the membrane-spanning complexes of the tight junctions, adherens junctions, and desmosomes ensuring its integrity. Tight junction proteins, like occludin, tricellulin, and the claudin family isoforms, play prominent roles as barriers to unrestricted paracellular transport. The past decade has witnessed major advances in our understanding of the architecture and function of epithelial tight junctions. While it has been long appreciated that microbes, notably bacterial and viral pathogens, target and disrupt junctional complexes and alter paracellular permeability, the precise mechanisms remain to be defined. Notably, renewed efforts will be required to interpret the available data on pathogen-mediated barrier disruption in the context of the most recent findings on tight junction structure and function. While much of the focus has been on pathogen-induced dysregulation of junctional complexes, commensal microbiota and their products may influence paracellular permeability and contribute to the normal physiology of the gut. Finally, microbes and their products have become important tools in exploring host systems, including the junctional properties of epithelial cells. © 2018 American Physiological Society. Compr Physiol 8:823-842, 2018. Copyright © 2018 American Physiological Society. All rights reserved.

Calcium transient prevalence across the dendritic arbour predicts place field properties.

PubMed

Sheffield, Mark E J; Dombeck, Daniel A

2015-01-08

Establishing the hippocampal cellular ensemble that represents an animal's environment involves the emergence and disappearance of place fields in specific CA1 pyramidal neurons, and the acquisition of different spatial firing properties across the active population. While such firing flexibility and diversity have been linked to spatial memory, attention and task performance, the cellular and network origin of these place cell features is unknown. Basic integrate-and-fire models of place firing propose that such features result solely from varying inputs to place cells, but recent studies suggest instead that place cells themselves may play an active role through regenerative dendritic events. However, owing to the difficulty of performing functional recordings from place cell dendrites, no direct evidence of regenerative dendritic events exists, leaving any possible connection to place coding unknown. Using multi-plane two-photon calcium imaging of CA1 place cell somata, axons and dendrites in mice navigating a virtual environment, here we show that regenerative dendritic events do exist in place cells of behaving mice, and, surprisingly, their prevalence throughout the arbour is highly spatiotemporally variable. Furthermore, we show that the prevalence of such events predicts the spatial precision and persistence or disappearance of place fields. This suggests that the dynamics of spiking throughout the dendritic arbour may play a key role in forming the hippocampal representation of space.

Alpha Lipoamide Ameliorates Motor Deficits and Mitochondrial Dynamics in the Parkinson's Disease Model Induced by 6-Hydroxydopamine.

PubMed

Zhou, Bo; Wen, Min; Lin, Xin; Chen, Yun-Hua; Gou, Yun; Li, Yong; Zhang, Yi; Li, Hong-Wei; Tang, Lei

2018-05-01

The precise mechanisms underlying neuronal injury in Parkinson's disease (PD) are not yet fully elucidated; however, evidence from the in vitro and in vivo PD models suggest that mitochondrial dysfunction may play a major role in PD pathogenesis. Alpha lipoamide, a neutral amide derivative of the lipoic acid, is a better cofactor for mitochondrial dehydrogenase with a stronger protective effect on mitochondria than lipoic acid. Identification of these protective effects of alpha lipoamide on mitochondria, together with the evidence that mitochondrial dysfunction plays a critical role in PD, we speculate that alpha lipoamide may exert a protective effect in PD by regulating the mitochondrial function. The present study investigated the neuroprotective effects of alpha lipoamide in an animal model of PD induced by 6-hydroxydopamine (6-OHDA). The results demonstrated that alpha lipoamide could significantly antagonize the 6-OHDA-induced behavioral damages; restore ATP levels in the midbrain; and also improve the fragmentation, vacuolization, and morphology of the mitochondria. The results of Western blot indicated that alpha lipoamide significantly restored the number of dopaminergic neurons in midbrain and substantially recovered the balance between mitochondrial fission, fusion, and transport. In conclusion, the results demonstrated that alpha lipoamide might exert a significant neuroprotective effect in the animal model of PD by regulation of the dynamic properties of mitochondria.

Calcium transient prevalence across the dendritic arbor predicts place field properties

PubMed Central

Sheffield, Mark E. J.; Dombeck, Daniel A.

2014-01-01

Establishing the hippocampal cellular ensemble that represents an animal’s environment involves the emergence and disappearance of place fields in specific CA1 pyramidal neurons1–4, and the acquisition of different spatial firing properties across the active population5. While such firing flexibility and diversity have been linked to spatial memory, attention and task performance6,7, the cellular and network origin of these place cell features is unknown. Basic integrate-and-fire models of place firing propose that such features result solely from varying inputs to place cells8,9, but recent studies3,10 instead suggest that place cells themselves may play an active role through regenerative dendritic events. However, due to the difficulty of performing functional recordings from place cell dendrites, no direct evidence of regenerative dendritic events exists, leaving any possible connection to place coding unknown. Using multi-plane two-photon calcium imaging of CA1 place cell somata, axons, and dendrites in mice navigating a virtual environment, we show that regenerative dendritic events do exist in place cells of behaving mice and, surprisingly, their prevalence throughout the arbor is highly spatiotemporally variable. Further, we show that the prevalence of such events predicts the spatial precision and persistence or disappearance of place fields. This suggests that the dynamics of spiking throughout the dendritic arbor may play a key role in forming the hippocampal representation of space. PMID:25363782

Effect of memantine on the levels of glial cells, neuropeptides, and peptide-degrading enzymes in rat brain regions of ibotenic acid-treated alzheimer's disease model.

PubMed

Ahmed, M M; Hoshino, H; Chikuma, T; Yamada, M; Kato, T

2004-01-01

It has been implicated that glia activation plays a critical role in the progression of Alzheimer's disease (AD). However, the precise mechanism of glia activation is not clearly understood yet. In our present studies, we confirmed our previous results where change the levels of neuropeptides and peptidases in ibotenic acid (IBO) infusion into the rat nucleus basalis magnocellularis, an animal model of AD. Furthermore, we extended our study to investigate a possible protection effect of co-administration on the changes of neuropeptides, and neuronal and glial cells in IBO-infused rat brain by memantine treatment. The levels of substance P and somatostatin were decreased in the striatum and frontal cortex 1 week after IBO infusion, and recovered to the control level by memantine treatment, indicating the involvement of neuropeptides in AD pathology. Furthermore, the immunohistochemical and enzymatic studies of GFAP and CD 11b, and peptidylarginine deiminase, markers of glia, in the striatum and frontal cortex showed the increase in IBO-treated rat brain as compared with controls, while co-administration of memantine and IBO no increase of astrocytes and microglia activation was observed. The present biochemical and immunohistochemical results suggest that glia activation might play an important role to the pathology of AD, and correlate with the changes of neuropeptide levels in AD brain that is recovered by memantine treatment.

Repulsive nature of optical potentials for high-energy heavy-ion scattering

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

Furumoto, T.; Sakuragi, Y.; Yamamoto, Y.

2010-10-15

The recent works by the present authors predicted that the real part of heavy-ion optical potentials changes its character from attraction to repulsion around the incident energy per nucleon E/A=200-300 MeV on the basis of the complex G-matrix interaction and the double-folding model (DFM) and revealed that the three-body force plays an important role there. In the present paper, we have precisely analyzed the energy dependence of the calculated DFM potentials and its relation to the elastic-scattering angular distributions in detail in the case of the {sup 12}C+{sup 12}C system in the energy range of E/A=100-400 MeV. The tensor forcemore » contributes substantially to the energy dependence of the real part of the DFM potentials and plays an important role to lower the attractive-to-repulsive transition energy. The nearside and farside (N/F) decompositions of the elastic-scattering amplitudes clarify the close relation between the attractive-to-repulsive transition of the potentials and the characteristic evolution of the calculated angular distributions with the increase of the incident energy. Based on the present analysis, we propose experimental measurements for the predicted strong diffraction phenomena of the elastic-scattering angular distribution caused by the N/F interference around the attractive-to-repulsive transition energy together with the reduced diffractions below and above the transition energy.« less

Engaging undergraduate students in hadron physics research and instrumentation

NASA Astrophysics Data System (ADS)

Horn, Tanja

2017-09-01

Nuclear physics research is fundamental to our understanding of the visible universe and at the same time intertwined with our daily life. Nuclear physics studies the origin and structure of the atomic nuclei in terms of their basic constituents, the quarks and gluons. Atoms and molecules would not exist without underlying quark-gluon interactions, which build nearly all the mass of the visible universe from an assembly of massless gluons and nearly-massless quarks. The study of hadron structure with electromagnetic probes through exclusive and semi-inclusive scattering experiments carried out at the 12 GeV Jefferson Laboratory plays an important role in this effort. In particular, planned precision measurements of pion and kaon form factors and longitudinal-transverse separated deep exclusive pion and kaon electroproduction cross sections to the highest momentum transfers achievable play an important role in understanding hadron structure and masses and provide essential constraints for 3D hadron imaging. While a growing fraction of nuclear physics research is carried out at large international laboratories, individual university research groups play critical roles in the success of that research. These include data analysis projects and the development of state-of-the-art instrumentation demanded by increasingly sophisticated experiments. These efforts are empowered by the creativity of university faculty, staff, postdocs, and provide students with unique hands-on experience. As an example, an aerogel Cherenkov detector enabling strangeness physics research in Hall C at Jefferson Lab was constructed at the Catholic University of America with the help of 16 undergraduate and high school students. The ''Conference Experience for Undergraduates'' (CEU) provides a venue for these students who have conducted research in nuclear physics. This presentation will present the experiences of one of the participants in the first years of the CEU, her current research program in hadronic physics, and her current and former students who have been participating in more recent CEU events. Supported in part by NSF Grants PHY1714133, PHY1306227 and PHY1306418.

Rhythm in joint action: psychological and neurophysiological mechanisms for real-time interpersonal coordination

PubMed Central

Keller, Peter E.; Novembre, Giacomo; Hove, Michael J.

2014-01-01

Human interaction often requires simultaneous precision and flexibility in the coordination of rhythmic behaviour between individuals engaged in joint activity, for example, playing a musical duet or dancing with a partner. This review article addresses the psychological processes and brain mechanisms that enable such rhythmic interpersonal coordination. First, an overview is given of research on the cognitive-motor processes that enable individuals to represent joint action goals and to anticipate, attend and adapt to other's actions in real time. Second, the neurophysiological mechanisms that underpin rhythmic interpersonal coordination are sought in studies of sensorimotor and cognitive processes that play a role in the representation and integration of self- and other-related actions within and between individuals' brains. Finally, relationships between social–psychological factors and rhythmic interpersonal coordination are considered from two perspectives, one concerning how social-cognitive tendencies (e.g. empathy) affect coordination, and the other concerning how coordination affects interpersonal affiliation, trust and prosocial behaviour. Our review highlights musical ensemble performance as an ecologically valid yet readily controlled domain for investigating rhythm in joint action. PMID:25385772

miR-122 does not impact recognition of the HCV genome by innate sensors of RNA but rather protects the 5' end from the cellular pyrophosphatases, DOM3Z and DUSP11.

PubMed

Amador-Cañizares, Yalena; Bernier, Annie; Wilson, Joyce A; Sagan, Selena M

2018-06-01

Hepatitis C virus (HCV) recruits two molecules of the liver-specific microRNA-122 (miR-122) to the 5' end of its genome. This interaction promotes viral RNA accumulation, but the precise mechanism(s) remain incompletely understood. Previous studies suggest that miR-122 is able to protect the HCV genome from 5' exonucleases (Xrn1/2), but this protection is not sufficient to account for the effect of miR-122 on HCV RNA accumulation. Thus, we investigated whether miR-122 was also able to protect the viral genome from innate sensors of RNA or cellular pyrophosphatases. We found that miR-122 does not play a protective role against recognition by PKR, RIG-I-like receptors, or IFITs 1 and 5. However, we found that knockdown of both the cellular pyrophosphatases, DOM3Z and DUSP11, was able to rescue viral RNA accumulation of subgenomic replicons in the absence of miR-122. Nevertheless, pyrophosphatase knockdown increased but did not restore viral RNA accumulation of full-length HCV RNA in miR-122 knockout cells, suggesting that miR-122 likely plays an additional role(s) in the HCV life cycle, beyond 5' end protection. Overall, our results support a model in which miR-122 stabilizes the HCV genome by shielding its 5' terminus from cellular pyrophosphatase activity and subsequent turnover by exonucleases (Xrn1/2).

PSMA PET and radionuclide therapy in prostate cancer

PubMed Central

Bouchelouche, Kirsten; Turkbey, Baris; Choyke, Peter L.

2016-01-01

Prostate cancer (Pca) is the most common malignancy in men and a major cause of cancer death. Accurate imaging plays an important role in diagnosis, staging, restaging, detection of biochemical recurrence, and for therapy of PCa patients. Since no effective treatment is available for advanced PCa, there is an urgent need to develop new and more effective therapeutic strategies. In order to optimize treatment outcome, especially in high risk PCa patients, therapy of PCa is moving rapidly towards personalization. Medical imaging, including positron emission tomography (PET)/computed tomography (CT), plays an important role in personalized medicine in oncology. In the recent years, much focus has been on prostate specific membrane antigen (PSMA) as a promising target for imaging and therapy with radionuclides, since it is upregulated in most PCa. In the prostate, one potential role for PSMA PET imaging is to help guiding focal therapy. Several studies have shown great potential of PSMA PET/CT for initial staging, lymph node staging, and detection of recurrence of PCa, even at very low PSA values after primary therapy. Furthermore, studies have shown that PSMA PET/CT has a higher detection rate than choline PET/CT. Radiolabeled PSMA ligands for therapy show promise in several studies with metastatic PCa, and is an area of active investigation. The “Image and treat” strategy, with radiolabeled PSMA ligands, has the potential to improve the treatment outcome of PCa patients, and is paving the way for precision medicine in PCa. The aim of this review is to give an overview of recent advancement in PSMA PET and radionuclide therapy of PCa. PMID:27825432

Cardioprotective role of P38 MAPK during myocardial infarction via parallel activation of α-crystallin B and Nrf2.

PubMed

Mitra, Arkadeep; Ray, Aramita; Datta, Ritwik; Sengupta, Shantanu; Sarkar, Sagartirtha

2014-09-01

Myocardial infarction (MI) is defined as cardiac cell death due to prolonged ischemia. Although necrotic cell death was considered to be solely responsible for myocyte death during MI, it was recently revealed that apoptosis also plays its part in this death process. Our laboratory has recently shown that endoplasmic reticulum (ER) stress-induced apoptosis is the predominant route for apoptosis during MI and the conventional mitochondrial pathway is bypassed by activation of a small heat shock protein α-crystallin B (CRYAB). Since CRYAB is a direct target of P38 mitogen-activated protein kinase (MAPK) cascade, we were prompted to check the role of P38 MAPK in 20-week-old male Wister rats immediately after infarct formation. Interestingly, parallel activation of mitochondrial apoptotic pathway with an increase in ER stress-induced apoptotic load was observed along with decreased activation of CRYAB and Nrf2 (a pro-survival protein activated in response to ER stress) in MI rats treated with SB203580, a specific inhibitor of P38α and P38β compared to the MI alone. As a cumulative effect, this inhibitor treatment also resulted in significant increase in the levels of caspase3 activity and TUNEL positivity, the end point apoptotic markers. Furthermore, SB203580-treated hypoxic adult cardiomyocytes showed formation of desmin aggregates which were previously associated with impaired cardiac function. Thus, this study shows for the first time the precise mechanism by which P38 MAPK plays a pro-survival role and confers protection of cardiomyocytes, during infarct formation. © 2014 Wiley Periodicals, Inc.

Improving BeiDou precise orbit determination using observations of onboard MEO satellite receivers

NASA Astrophysics Data System (ADS)

Ge, Haibo; Li, Bofeng; Ge, Maorong; Shen, Yunzhong; Schuh, Harald

2017-12-01

In recent years, the precise orbit determination (POD) of the regional Chinese BeiDou Navigation Satellite System (BDS) has been a hot spot because of its special constellation consisting of five geostationary earth orbit (GEO) satellites and five inclined geosynchronous satellite orbit (IGSO) satellites besides four medium earth orbit (MEO) satellites since the end of 2012. GEO and IGSO satellites play an important role in regional BDS applications. However, this brings a great challenge to the POD, especially for the GEO satellites due to their geostationary orbiting. Though a number of studies have been carried out to improve the POD performance of GEO satellites, the result is still much worse than that of IGSO and MEO, particularly in the along-track direction. The major reason is that the geostationary characteristic of a GEO satellite results in a bad geometry with respect to the ground tracking network. In order to improve the tracking geometry of the GEO satellites, a possible strategy is to mount global navigation satellite system (GNSS) receivers on MEO satellites to collect the signals from GEO/IGSO GNSS satellites so as that these observations can be used to improve GEO/IGSO POD. We extended our POD software package to simulate all the related observations and to assimilate the MEO-onboard GNSS observations in orbit determination. Based on GPS and BDS constellations, simulated studies are undertaken for various tracking scenarios. The impact of the onboard GNSS observations is investigated carefully and presented in detail. The results show that MEO-onboard observations can significantly improve the orbit precision of GEO satellites from metres to decimetres, especially in the along-track direction. The POD results of IGSO satellites also benefit from the MEO-onboard data and the precision can be improved by more than 50% in 3D direction.

Optimization Techniques for Improving the Precision of Isotopic Analysis by Thermal Ionization Mass Spectrometry

NASA Astrophysics Data System (ADS)

Wang, G. Q.; Xu, J. F.; Wu-Yang, S. Q.

2016-12-01

Operation of instruments and preparation of samples are also significant factors that can affect the precision of TIMS analyses, in addition to instrument hardware. We have reviewed the isotopic data of several standard materials at our TIMS lab for 5 years. It is suggested that several optimization techniques should be used in order to obtain high-precision isotopic ratio data: (1) It is important to choose a suitable filament material for isotopic measurements. We have established that W filament is likely the most efficient for ionizing Sr when selecting from W, Re, and Ta; meanwhile, Re filament can produce a higher intensity for Nd isotopes than W and Ta filament can. It is concluded that the best TIMS signals are obtained for Sr using W signal-filaments and for Nd using Re double-filaments. (2) The preparation of the activator plays a key role in the analysis of some isotopic ratios. This study indicates that choosing a suitable activator can greatly elevate the precision of 206Pb/204Pb ratios during Pb isotopic measurements. We have suggested a new scheme to make an activator by using a mixture of 10% Si-gel + 7.5% H3PO3 + 82.5% H2O (weight %). (3) It is necessary to re-set the cup configuration to avoid cup degradation when operating for a long period of time (a year or more). We propose a new cup configuration to avoid this disadvantage during Sr isotopic analyses. (4) The contamination of 187Re and 185Re after using Re-filament could be eliminated by cleaning the ion source and baking the source housing.

On the convergence of ionospheric constrained precise point positioning (IC-PPP) based on undifferential uncombined raw GNSS observations.

PubMed

Zhang, Hongping; Gao, Zhouzheng; Ge, Maorong; Niu, Xiaoji; Huang, Ling; Tu, Rui; Li, Xingxing

2013-11-18

Precise Point Positioning (PPP) has become a very hot topic in GNSS research and applications. However, it usually takes about several tens of minutes in order to obtain positions with better than 10 cm accuracy. This prevents PPP from being widely used in real-time kinematic positioning services, therefore, a large effort has been made to tackle the convergence problem. One of the recent approaches is the ionospheric delay constrained precise point positioning (IC-PPP) that uses the spatial and temporal characteristics of ionospheric delays and also delays from an a priori model. In this paper, the impact of the quality of ionospheric models on the convergence of IC-PPP is evaluated using the IGS global ionospheric map (GIM) updated every two hours and a regional satellite-specific correction model. Furthermore, the effect of the receiver differential code bias (DCB) is investigated by comparing the convergence time for IC-PPP with and without estimation of the DCB parameter. From the result of processing a large amount of data, on the one hand, the quality of the a priori ionosphere delays plays a very important role in IC-PPP convergence. Generally, regional dense GNSS networks can provide more precise ionosphere delays than GIM and can consequently reduce the convergence time. On the other hand, ignoring the receiver DCB may considerably extend its convergence, and the larger the DCB, the longer the convergence time. Estimating receiver DCB in IC-PPP is a proper way to overcome this problem. Therefore, current IC-PPP should be enhanced by estimating receiver DCB and employing regional satellite-specific ionospheric correction models in order to speed up its convergence for more practical applications.

Precise Perforation and Scalable Production of Si Particles from Low-Grade Sources for High-Performance Lithium Ion Battery Anodes.

PubMed

Zong, Linqi; Jin, Yan; Liu, Chang; Zhu, Bin; Hu, Xiaozhen; Lu, Zhenda; Zhu, Jia

2016-11-09

Alloy anodes, particularly silicon, have been intensively pursued as one of the most promising anode materials for the next generation lithium-ion battery primarily because of high specific capacity (>4000 mAh/g) and elemental abundance. In the past decade, various nanostructures with porosity or void space designs have been demonstrated to be effective to accommodate large volume expansion (∼300%) and to provide stable solid electrolyte interphase (SEI) during electrochemical cycling. However, how to produce these building blocks with precise morphology control at large scale and low cost remains a challenge. In addition, most of nanostructured silicon suffers from poor Coulombic efficiency due to a large surface area and Li ion trapping at the surface coating. Here we demonstrate a unique nanoperforation process, combining modified ball milling, annealing, and acid treating, to produce porous Si with precise and continuous porosity control (from 17% to 70%), directly from low cost metallurgical silicon source (99% purity, ∼ $1/kg). The produced porous Si coated with graphene by simple ball milling can deliver a reversible specific capacity of 1250 mAh/g over 1000 cycles at the rate of 1C, with Coulombic efficiency of first cycle over 89.5%. The porous networks also provide efficient ion and electron pathways and therefore enable excellent rate performance of 880 mAh/g at the rate of 5C. Being able to produce particles with precise porosity control through scalable processes from low-grade materials, it is expected that this nanoperforation may play a role in the next generation lithium ion battery anodes, as well as many other potential applications such as optoelectronics and thermoelectrics.

A flux-gradient system for simultaneous measurement of the CH4, CO2, and H2O fluxes at a lake-air interface.

PubMed

Xiao, Wei; Liu, Shoudong; Li, Hanchao; Xiao, Qitao; Wang, Wei; Hu, Zhenghua; Hu, Cheng; Gao, Yunqiu; Shen, Jing; Zhao, Xiaoyan; Zhang, Mi; Lee, Xuhui

2014-12-16

Inland lakes play important roles in water and greenhouse gas cycling in the environment. This study aims to test the performance of a flux-gradient system for simultaneous measurement of the fluxes of water vapor, CO2, and CH4 at a lake-air interface. The concentration gradients over the water surface were measured with an analyzer based on the wavelength-scanned cavity ring-down spectroscopy technology, and the eddy diffusivity was measured with a sonic anemometer. Results of a zero-gradient test indicate a flux measurement precision of 4.8 W m(-2) for water vapor, 0.010 mg m(-2) s(-1) for CO2, and 0.029 μg m(-2) s(-1) for CH4. During the 620 day measurement period, 97%, 69%, and 67% of H2O, CO2, and CH4 hourly fluxes were higher in magnitude than the measurement precision, which confirms that the flux-gradient system had adequate precision for the measurement of the lake-air exchanges. This study illustrates four strengths of the flux-gradient method: (1) the ability to simultaneously measure the flux of H2O, CO2, and CH4; (2) negligibly small density corrections; (3) the ability to resolve small CH4 gradient and flux; and (4) continuous and noninvasive operation. The annual mean CH4 flux (1.8 g CH4 m(-2) year(-1)) at this hypereutrophic lake was close to the median value for inland lakes in the world (1.6 g CH4 m(-2) year(-1)). The system has adequate precision for CH4 flux for broad applications but requires further improvement to resolve small CO2 flux in many lakes.

The use of robotics in otolaryngology-head and neck surgery: a systematic review.

PubMed

Maan, Zeshaan N; Gibbins, Nick; Al-Jabri, Talal; D'Souza, Alwyn R

2012-01-01

Robotic surgery has become increasingly used due to its enhancement of visualization, precision, and articulation. It eliminates many of the problems encountered with conventional minimally invasive techniques and has been shown to result in reduced blood loss and complications. The rise in endoscopic procedures in otolaryngology-head and neck surgery, and associated difficulties, suggests that robotic surgery may have a role to play. To determine whether robotic surgery conveys any benefits compared to conventional minimally invasive approaches, specifically looking at precision, operative time, and visualization. A systematic review of the literature with a defined search strategy. Searches of MEDLINE, EMBASE and CENTRAL using strategy: ((robot* OR (robot*AND surgery)) AND (ent OR otolaryngology)) to November 2010. Articles reviewed by authors and data compiled in tables for analysis. There were 33 references included in the study. Access and visualization were regularly mentioned as key benefits, though no objective data has been recorded in any study. Once initial setup difficulties were overcome, operative time was shown to decrease with robotic surgery, except in one controlled series of thyroid surgeries. Precision was also highlighted as an advantage, particularly in otological and skull base surgery. Postoperative outcomes were considered equivalent to or better than conventional surgery. Cost was the biggest drawback. The evidence base to date suggests there are benefits to robotic surgery in OHNS, particularly with regards to access, precision, and operative time but there is a lack of controlled, prospective studies with objective outcome measures. In addition, economic feasibility studies must be carried out before a robotic OHNS service is established. Copyright © 2012 Elsevier Inc. All rights reserved.

On the Convergence of Ionospheric Constrained Precise Point Positioning (IC-PPP) Based on Undifferential Uncombined Raw GNSS Observations

PubMed Central

Zhang, Hongping; Gao, Zhouzheng; Ge, Maorong; Niu, Xiaoji; Huang, Ling; Tu, Rui; Li, Xingxing

2013-01-01

Precise Point Positioning (PPP) has become a very hot topic in GNSS research and applications. However, it usually takes about several tens of minutes in order to obtain positions with better than 10 cm accuracy. This prevents PPP from being widely used in real-time kinematic positioning services, therefore, a large effort has been made to tackle the convergence problem. One of the recent approaches is the ionospheric delay constrained precise point positioning (IC-PPP) that uses the spatial and temporal characteristics of ionospheric delays and also delays from an a priori model. In this paper, the impact of the quality of ionospheric models on the convergence of IC-PPP is evaluated using the IGS global ionospheric map (GIM) updated every two hours and a regional satellite-specific correction model. Furthermore, the effect of the receiver differential code bias (DCB) is investigated by comparing the convergence time for IC-PPP with and without estimation of the DCB parameter. From the result of processing a large amount of data, on the one hand, the quality of the a priori ionosphere delays plays a very important role in IC-PPP convergence. Generally, regional dense GNSS networks can provide more precise ionosphere delays than GIM and can consequently reduce the convergence time. On the other hand, ignoring the receiver DCB may considerably extend its convergence, and the larger the DCB, the longer the convergence time. Estimating receiver DCB in IC-PPP is a proper way to overcome this problem. Therefore, current IC-PPP should be enhanced by estimating receiver DCB and employing regional satellite-specific ionospheric correction models in order to speed up its convergence for more practical applications. PMID:24253190

Targeted mutagenesis using zinc-finger nucleases in perennial fruit trees.

PubMed

Peer, Reut; Rivlin, Gil; Golobovitch, Sara; Lapidot, Moshe; Gal-On, Amit; Vainstein, Alexander; Tzfira, Tzvi; Flaishman, Moshe A

2015-04-01

Targeting a gene in apple or fig with ZFN, introduced by transient or stable transformation, should allow genome editing with high precision to advance basic science and breeding programs. Genome editing is a powerful tool for precise gene manipulation in any organism; it has recently been shown to be of great value for annual plants. Classical breeding strategies using conventional cross-breeding and induced mutations have played an important role in the development of new cultivars in fruit trees. However, fruit-tree breeding is a lengthy process with many limitations. Efficient and widely applied methods for targeted modification of fruit-tree genomes are not yet available. In this study, transgenic apple and fig lines carrying a zinc-finger nuclease (ZFNs) under the control of a heat-shock promoter were developed. Editing of a mutated uidA gene, following expression of the ZFN genes by heat shock, was confirmed by GUS staining and PCR product sequencing. Finally, whole plants with a repaired uidA gene due to deletion of a stop codon were regenerated. The ZFN-mediated gene modifications were stable and passed onto regenerants from ZFN-treated tissue cultures. This is the first demonstration of efficient and precise genome editing, using ZFN at a specific genomic locus, in two different perennial fruit trees-apple and fig. We conclude that targeting a gene in apple or fig with a ZFN introduced by transient or stable transformation should allow knockout of a gene of interest. Using this technology for genome editing allows for marker gene-independent and antibiotic selection-free genome engineering with high precision in fruit trees to advance basic science as well as nontransgenic breeding programs.

Investigation of visual fatigue/discomfort generated by S3D video using eye-tracking data

NASA Astrophysics Data System (ADS)

Iatsun, Iana; Larabi, Mohamed-Chaker; Fernandez-Maloigne, Christine

2013-03-01

Stereoscopic 3D is undoubtedly one of the most attractive content. It has been deployed intensively during the last decade through movies and games. Among the advantages of 3D are the strong involvement of viewers and the increased feeling of presence. However, the sanitary e ects that can be generated by 3D are still not precisely known. For example, visual fatigue and visual discomfort are among symptoms that an observer may feel. In this paper, we propose an investigation of visual fatigue generated by 3D video watching, with the help of eye-tracking. From one side, a questionnaire, with the most frequent symptoms linked with 3D, is used in order to measure their variation over time. From the other side, visual characteristics such as pupil diameter, eye movements ( xations and saccades) and eye blinking have been explored thanks to data provided by the eye-tracker. The statistical analysis showed an important link between blinking duration and number of saccades with visual fatigue while pupil diameter and xations are not precise enough and are highly dependent on content. Finally, time and content play an important role in the growth of visual fatigue due to 3D watching.

Understanding the potential of state-based public health genomics programs to mitigate disparities in access to clinical genetic services.

PubMed

Senier, Laura; Tan, Catherine; Smollin, Leandra; Lee, Rachael

2018-06-12

State health agencies (SHAs) have developed public health genomics (PHG) programs that play an instrumental role in advancing precision public health, but there is limited research on their approaches. This study examines how PHG programs attempt to mitigate or forestall health disparities and inequities in the utilization of genomic medicine. We compared PHG programs in three states: Connecticut, Michigan, and Utah. We analyzed 85 in-depth interviews with SHA internal and external collaborators and program documents. We employed a qualitative coding process to capture themes relating to health disparities and inequities. Each SHA implemented population-level approaches to identify individuals who carry genetic variants that increase risk of hereditary cancers. However, each SHA developed a unique strategy-which we label public health action repertoires-to reach specific subgroups who faced barriers in accessing genetic services. These strategies varied across states given demographics of the state population, state-level partnerships, and availability of healthcare services. Our findings illustrate the imperative of tailoring PHG programs to local demographic characteristics and existing community resources. Furthermore, our study highlights how integrating genomics into precision public health will require multilevel, multisector collaboration to optimize efficacy and equity.

Dynamical scales for multi-TeV top-pair production at the LHC

NASA Astrophysics Data System (ADS)

Czakon, Michał; Heymes, David; Mitov, Alexander

2017-04-01

We calculate all major differential distributions with stable top-quarks at the LHC. The calculation covers the multi-TeV range that will be explored during LHC Run II and beyond. Our results are in the form of high-quality binned distributions. We offer predictions based on three different parton distribution function (pdf) sets. In the near future we will make our results available also in the more flexible fastNLO format that allows fast re-computation with any other pdf set. In order to be able to extend our calculation into the multi-TeV range we have had to derive a set of dynamic scales. Such scales are selected based on the principle of fastest perturbative convergence applied to the differential and inclusive cross-section. Many observations from our study are likely to be applicable and useful to other precision processes at the LHC. With scale uncertainty now under good control, pdfs arise as the leading source of uncertainty for TeV top production. Based on our findings, true precision in the boosted regime will likely only be possible after new and improved pdf sets appear. We expect that LHC top-quark data will play an important role in this process.

The combination design for open and endoscopic surgery using fluorescence molecular imaging technology

NASA Astrophysics Data System (ADS)

Mao, Yamin; Jiang, Shixin; Ye, Jinzuo; An, Yu; Yang, Xin; Chi, Chongwei; Tian, Jie

2015-03-01

For clinical surgery, it is still a challenge to objectively determine tumor margins during surgery. With the development of medical imaging technology, fluorescence molecular imaging (FMI) method can provide real-time intraoperative tumor margin information. Furthermore, surgical navigation system based on FMI technology plays an important role for the aid of surgeons' precise tumor margin decision. However, detection depth is the most limitation exists in the FMI technique and the method convenient for either macro superficial detection or micro deep tissue detection is needed. In this study, we combined advantages of both open surgery and endoscopic imaging systems with FMI technology. Indocyanine green (ICG) experiments were performed to confirm the feasibility of fluorescence detection in our system. Then, the ICG signal was photographed in the detection area with our system. When the system connected with endoscope lens, the minimum quantity of ICG detected by our system was 0.195 ug. For aspect of C mount lens, the sensitivity of ICG detection with our system was 0.195ug. Our experiments results proved that it was feasible to detect fluorescence images with this combination method. Our system shows great potential in the clinical applications of precise dissection of various tumors

A novel knowledge-based potential for RNA 3D structure evaluation

NASA Astrophysics Data System (ADS)

Yang, Yi; Gu, Qi; Zhang, Ben-Gong; Shi, Ya-Zhou; Shao, Zhi-Gang

2018-03-01

Ribonucleic acids (RNAs) play a vital role in biology, and knowledge of their three-dimensional (3D) structure is required to understand their biological functions. Recently structural prediction methods have been developed to address this issue, but a series of RNA 3D structures are generally predicted by most existing methods. Therefore, the evaluation of the predicted structures is generally indispensable. Although several methods have been proposed to assess RNA 3D structures, the existing methods are not precise enough. In this work, a new all-atom knowledge-based potential is developed for more accurately evaluating RNA 3D structures. The potential not only includes local and nonlocal interactions but also fully considers the specificity of each RNA by introducing a retraining mechanism. Based on extensive test sets generated from independent methods, the proposed potential correctly distinguished the native state and ranked near-native conformations to effectively select the best. Furthermore, the proposed potential precisely captured RNA structural features such as base-stacking and base-pairing. Comparisons with existing potential methods show that the proposed potential is very reliable and accurate in RNA 3D structure evaluation. Project supported by the National Science Foundation of China (Grants Nos. 11605125, 11105054, 11274124, and 11401448).

Automatic detection and quantitative analysis of cells in the mouse primary motor cortex

NASA Astrophysics Data System (ADS)

Meng, Yunlong; He, Yong; Wu, Jingpeng; Chen, Shangbin; Li, Anan; Gong, Hui

2014-09-01

Neuronal cells play very important role on metabolism regulation and mechanism control, so cell number is a fundamental determinant of brain function. Combined suitable cell-labeling approaches with recently proposed three-dimensional optical imaging techniques, whole mouse brain coronal sections can be acquired with 1-μm voxel resolution. We have developed a completely automatic pipeline to perform cell centroids detection, and provided three-dimensional quantitative information of cells in the primary motor cortex of C57BL/6 mouse. It involves four principal steps: i) preprocessing; ii) image binarization; iii) cell centroids extraction and contour segmentation; iv) laminar density estimation. Investigations on the presented method reveal promising detection accuracy in terms of recall and precision, with average recall rate 92.1% and average precision rate 86.2%. We also analyze laminar density distribution of cells from pial surface to corpus callosum from the output vectorizations of detected cell centroids in mouse primary motor cortex, and find significant cellular density distribution variations in different layers. This automatic cell centroids detection approach will be beneficial for fast cell-counting and accurate density estimation, as time-consuming and error-prone manual identification is avoided.

Lidar Sensors for Autonomous Landing and Hazard Avoidance

NASA Technical Reports Server (NTRS)

Amzajerdian, Farzin; Petway, Larry B.; Hines, Glenn D.; Roback, Vincent E.; Reisse, Robert A.; Pierrottet, Diego F.

2013-01-01

Lidar technology will play an important role in enabling highly ambitious missions being envisioned for exploration of solar system bodies. Currently, NASA is developing a set of advanced lidar sensors, under the Autonomous Landing and Hazard Avoidance (ALHAT) project, aimed at safe landing of robotic and manned vehicles at designated sites with a high degree of precision. These lidar sensors are an Imaging Flash Lidar capable of generating high resolution three-dimensional elevation maps of the terrain, a Doppler Lidar for providing precision vehicle velocity and altitude, and a Laser Altimeter for measuring distance to the ground and ground contours from high altitudes. The capabilities of these lidar sensors have been demonstrated through four helicopter and one fixed-wing aircraft flight test campaigns conducted from 2008 through 2012 during different phases of their development. Recently, prototype versions of these landing lidars have been completed for integration into a rocket-powered terrestrial free-flyer vehicle (Morpheus) being built by NASA Johnson Space Center. Operating in closed-loop with other ALHAT avionics, the viability of the lidars for future landing missions will be demonstrated. This paper describes the ALHAT lidar sensors and assesses their capabilities and impacts on future landing missions.

Controlling T c of Iridium films using interfacial proximity effects

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

Hennings-Yeomans, R; Chang, CL; Ding, J

High precision calorimetry using superconducting transition edge sensors requires the use of superconducting films with a suitable T c, depending on the application. To advance high-precision macrocalorimetry, we require low-T c films that are easy to fabricate. A simple and effective way to suppress T c of superconducting Iridium through the proximity effect is demonstrated by using Ir/Pt bilayers as well as Au/Ir/Au trilayers. While Ir/Au films fabricated by applying heat to the substrate during Ir deposition have been used in the past for superconducting sensors, we present results of T c suppression on Iridium by deposition at room temperature in Au/Ir/Au trilayers and Ir/Pt bilayers in the range ofmore » $$\\sim$$20-100~mK. Measurements of the relative impedance between the Ir/Pt bilayers and Au/Ir/Au trilayers fabricated show factor of $$\\sim$$10 higher values in the Ir/Pt case. These new films could play a key role in the development of scalable superconducting transition edge sensors that require low-T c films to minimize heat capacity and maximize energy resolution, while keeping high-yield fabrication methods.« less

Spontaneously formed high-performance charge-transport layers of organic single-crystal semiconductors on precisely synthesized insulating polymers

NASA Astrophysics Data System (ADS)

Makita, Tatsuyuki; Sasaki, Masayuki; Annaka, Tatsuro; Sasaki, Mari; Matsui, Hiroyuki; Mitsui, Chikahiko; Kumagai, Shohei; Watanabe, Shun; Hayakawa, Teruaki; Okamoto, Toshihiro; Takeya, Jun

2017-04-01

Charge-transporting semiconductor layers with high carrier mobility and low trap-density, desired for high-performance organic transistors, are spontaneously formed as a result of thermodynamic phase separation from a blend of π-conjugated small molecules and precisely synthesized insulating polymers dissolved in an aromatic solvent. A crystal film grows continuously to the size of centimeters, with the critical conditions of temperature, concentrations, and atmosphere. It turns out that the molecular weight of the insulating polymers plays an essential role in stable film growth and interfacial homogeneity at the phase separation boundary. Fabricating the transistor devices directly at the semiconductor-insulator boundaries, we demonstrate that the mixture of 3,11-didecyldinaphtho[2,3-d:2',3'-d']benzo[1,2-b:4,5-b']dithiophene and poly(methyl methacrylate) with the optimized weight-average molecular weight shows excellent device performances. The spontaneous phase separation with a one-step fabrication process leads to a high mobility up to 10 cm2 V-1 s-1 and a low subthreshold swing of 0.25 V dec-1 even without any surface treatment such as self-assembled monolayer modifications on oxide gate insulators.

Qualitative and Quantitative Analysis of the Major Constituents in Chinese Medical Preparation Lianhua-Qingwen Capsule by UPLC-DAD-QTOF-MS

PubMed Central

Jia, Weina; Wang, Chunhua; Wang, Yuefei; Pan, Guixiang; Jiang, Miaomiao; Li, Zheng; Zhu, Yan

2015-01-01

Lianhua-Qingwen capsule (LQC) is a commonly used Chinese medical preparation to treat viral influenza and especially played a very important role in the fight against severe acute respiratory syndrome (SARS) in 2002-2003 in China. In this paper, a rapid ultraperformance liquid chromatography coupled with diode-array detector and quadrupole time-of-flight mass spectrometry (UPLC-DAD-QTOF-MS) method was established for qualitative and quantitative analysis of the major constituents of LQC. A total of 61 compounds including flavonoids, phenylpropanoids, anthraquinones, triterpenoids, iridoids, and other types of compounds were unambiguously or tentatively identified by comparing the retention times and accurate mass measurement with reference compounds or literature data. Among them, twelve representative compounds were further quantified as chemical markers in quantitative analysis, including salidroside, chlorogenic acid, forsythoside E, cryptochlorogenic acid, amygdalin, sweroside, hyperin, rutin, forsythoside A, phillyrin, rhein, and glycyrrhizic acid. The UPLC-DAD method was evaluated with linearity, limit of detection (LOD), limit of quantification (LOQ), precision, stability, repeatability, and recovery tests. The results showed that the developed quantitative method was linear, sensitive, and precise for the quality control of LQC. PMID:25654135

Intraoperative imaging-guided cancer surgery: from current fluorescence molecular imaging methods to future multi-modality imaging technology.

PubMed

Chi, Chongwei; Du, Yang; Ye, Jinzuo; Kou, Deqiang; Qiu, Jingdan; Wang, Jiandong; Tian, Jie; Chen, Xiaoyuan

2014-01-01

Cancer is a major threat to human health. Diagnosis and treatment using precision medicine is expected to be an effective method for preventing the initiation and progression of cancer. Although anatomical and functional imaging techniques such as radiography, computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography (PET) have played an important role for accurate preoperative diagnostics, for the most part these techniques cannot be applied intraoperatively. Optical molecular imaging is a promising technique that provides a high degree of sensitivity and specificity in tumor margin detection. Furthermore, existing clinical applications have proven that optical molecular imaging is a powerful intraoperative tool for guiding surgeons performing precision procedures, thus enabling radical resection and improved survival rates. However, detection depth limitation exists in optical molecular imaging methods and further breakthroughs from optical to multi-modality intraoperative imaging methods are needed to develop more extensive and comprehensive intraoperative applications. Here, we review the current intraoperative optical molecular imaging technologies, focusing on contrast agents and surgical navigation systems, and then discuss the future prospects of multi-modality imaging technology for intraoperative imaging-guided cancer surgery.

Six-Port Based Interferometry for Precise Radar and Sensing Applications.

PubMed

Koelpin, Alexander; Lurz, Fabian; Linz, Sarah; Mann, Sebastian; Will, Christoph; Lindner, Stefan

2016-09-22

Microwave technology plays a more important role in modern industrial sensing applications. Pushed by the significant progress in monolithic microwave integrated circuit technology over the past decades, complex sensing systems operating in the microwave and even millimeter-wave range are available for reasonable costs combined with exquisite performance. In the context of industrial sensing, this stimulates new approaches for metrology based on microwave technology. An old measurement principle nearly forgotten over the years has recently gained more and more attention in both academia and industry: the six-port interferometer. This paper reviews the basic concept, investigates promising applications in remote, as well as contact-based sensing and compares the system with state-of-the-art metrology. The significant advantages will be discussed just as the limitations of the six-port architecture. Particular attention will be paid to impairment effects and non-ideal behavior, as well as compensation and linearization concepts. It will be shown that in application fields, like remote distance sensing, precise alignment measurements, as well as interferometrically-evaluated mechanical strain analysis, the six-port architecture delivers extraordinary measurement results combined with high measurement data update rates for reasonable system costs. This makes the six-port architecture a promising candidate for industrial metrology.

MicroRNA applications for prostate, ovarian and breast cancer in the era of precision medicine

PubMed Central

Smith, Bethany; Agarwal, Priyanka

2017-01-01

The high degree of conservation in microRNA from Caenorhabditis elegans to humans has enabled relatively rapid implementation of findings in model systems to the clinic. The convergence of the capacity for genomic screening being implemented in the prevailing precision medicine initiative and the capabilities of microRNA to address these changes holds significant promise. However, prostate, ovarian and breast cancers are heterogeneous and face issues of evolving therapeutic resistance. The transforming growth factor-beta (TGFβ) signaling axis plays an important role in the progression of these cancers by regulating microRNAs. Reciprocally, microRNAs regulate TGFβ actions during cancer progression. One must consider the expression of miRNA in the tumor microenvironment a source of biomarkers of disease progression and a viable target for therapeutic targeting. The differential expression pattern of microRNAs in health and disease, therapeutic response and resistance has resulted in its application as robust biomarkers. With two microRNA mimetics in ongoing restorative clinical trials, the paradigm for future clinical studies rests on the current observational trials to validate microRNA markers of disease progression. Some of today’s biomarkers can be translated to the next generation of microRNA-based therapies. PMID:28289080

Parametric Optimization Of Gas Metal Arc Welding Process By Using Grey Based Taguchi Method On Aisi 409 Ferritic Stainless Steel

NASA Astrophysics Data System (ADS)

Ghosh, Nabendu; Kumar, Pradip; Nandi, Goutam

2016-10-01

Welding input process parameters play a very significant role in determining the quality of the welded joint. Only by properly controlling every element of the process can product quality be controlled. For better quality of MIG welding of Ferritic stainless steel AISI 409, precise control of process parameters, parametric optimization of the process parameters, prediction and control of the desired responses (quality indices) etc., continued and elaborate experiments, analysis and modeling are needed. A data of knowledge - base may thus be generated which may be utilized by the practicing engineers and technicians to produce good quality weld more precisely, reliably and predictively. In the present work, X-ray radiographic test has been conducted in order to detect surface and sub-surface defects of weld specimens made of Ferritic stainless steel. The quality of the weld has been evaluated in terms of yield strength, ultimate tensile strength and percentage of elongation of the welded specimens. The observed data have been interpreted, discussed and analyzed by considering ultimate tensile strength ,yield strength and percentage elongation combined with use of Grey-Taguchi methodology.

Intraoperative Imaging-Guided Cancer Surgery: From Current Fluorescence Molecular Imaging Methods to Future Multi-Modality Imaging Technology

PubMed Central

Chi, Chongwei; Du, Yang; Ye, Jinzuo; Kou, Deqiang; Qiu, Jingdan; Wang, Jiandong; Tian, Jie; Chen, Xiaoyuan

2014-01-01

Cancer is a major threat to human health. Diagnosis and treatment using precision medicine is expected to be an effective method for preventing the initiation and progression of cancer. Although anatomical and functional imaging techniques such as radiography, computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography (PET) have played an important role for accurate preoperative diagnostics, for the most part these techniques cannot be applied intraoperatively. Optical molecular imaging is a promising technique that provides a high degree of sensitivity and specificity in tumor margin detection. Furthermore, existing clinical applications have proven that optical molecular imaging is a powerful intraoperative tool for guiding surgeons performing precision procedures, thus enabling radical resection and improved survival rates. However, detection depth limitation exists in optical molecular imaging methods and further breakthroughs from optical to multi-modality intraoperative imaging methods are needed to develop more extensive and comprehensive intraoperative applications. Here, we review the current intraoperative optical molecular imaging technologies, focusing on contrast agents and surgical navigation systems, and then discuss the future prospects of multi-modality imaging technology for intraoperative imaging-guided cancer surgery. PMID:25250092

Geomagnetic referencing in the arctic environment

USGS Publications Warehouse

Podjono, Benny; Beck, Nathan; Buchanan, Andrew; Brink, Jason; Longo, Joseph; Finn, Carol A.; Worthington, E. William

2011-01-01

Geomagnetic referencing is becoming an increasingly attractive alternative to north-seeking gyroscopic surveys to achieve the precise wellbore positioning essential for success in today's complex drilling programs. However, the greater magnitude of variations in the geomagnetic environment at higher latitudes makes the application of geomagnetic referencing in those areas more challenging. Precise, real-time data on those variations from relatively nearby magnetic observatories can be crucial to achieving the required accuracy, but constructing and operating an observatory in these often harsh environments poses a number of significant challenges. Operational since March 2010, the Deadhorse Magnetic Observatory (DED), located in Deadhorse, Alaska, was created through collaboration between the United States Geological Survey (USGS) and a leading oilfield services supply company. DED was designed to produce real-time geomagnetic data at the required level of accuracy, and to do so reliably under the extreme temperatures and harsh weather conditions often experienced in the area. The observatory will serve a number of key scientific communities as well as the oilfield drilling industry, and has already played a vital role in the success of several commercial ventures in the area, providing essential, accurate data while offering significant cost and time savings, compared with traditional surveying techniques.

Geomagnetic referencing in the arctic environment

USGS Publications Warehouse

Poedjono, B.; Beck, N.; Buchanan, A. C.; Brink, J.; Longo, J.; Finn, C.A.; Worthington, E.W.

2011-01-01

Geomagnetic referencing is becoming an increasingly attractive alternative to north-seeking gyroscopic surveys to achieve the precise wellbore positioning essential for success in today's complex drilling programs. However, the greater magnitude of variations in the geomagnetic environment at higher latitudes makes the application of geomagnetic referencing in those areas more challenging. Precise, real-time data on those variations from relatively nearby magnetic observatories can be crucial to achieving the required accuracy, but constructing and operating an observatory in these often harsh environments poses a number of significant challenges. Operational since March 2010, the Deadhorse Magnetic Observatory (DED), located in Deadhorse, Alaska, was created through collaboration between the United States Geological Survey (USGS) and a leading oilfield services supply company. DED was designed to produce real-time geomagnetic data at the required level of accuracy, and to do so reliably under the extreme temperatures and harsh weather conditions often experienced in the area. The observatory will serve a number of key scientific communities as well as the oilfield drilling industry, and has already played a vital role in the success of several commercial ventures in the area, providing essential, accurate data while offering significant cost and time savings, compared with traditional surveying techniques. Copyright 2011, Society of Petroleum Engineers.