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1. Variability and trends in the potential vorticity (PV)-gradient dynamical tropopause

Author: K. Turhal, F. Plöger, J. Clemens, T. Birner, F. Weyland, P. Konopka, and P. Hoor
Subjects: Physics, QC1-999, Chemistry, QD1-999
Abstract: The dynamical tropopause acts as a transport barrier between the tropical upper troposphere and extratropical lowermost stratosphere and is characterized by steep gradients in potential vorticity (PV) along an isentropic surface. Hence, the latitudinal separation between the dynamical tropopause in the Northern Hemisphere and Southern Hemisphere can be used as a metric of upper-tropospheric width for assessing climate change impacts. Here, we obtain the PV-gradient-based dynamical tropopause (PVG tropopause) from four meteorological satellite-era reanalyses (ERA5, ERA-Interim, JRA-55, MERRA-2) and investigate its climatology, variability and long-term trends from 1980 to 2017. Our results show a distinct seasonal cycle with larger PV values and a poleward movement of the PVG tropopause in summer. The climatological tropopause PV values are substantially different between different reanalyses, but the tropopause latitude is similar. Significant interannual variability in the PVG tropopause latitude is related to the El Niño–Southern Oscillation (ENSO) and weaker variability also to the quasi-biennial oscillation (QBO) and is consistently represented in reanalyses. In particular, El Niño correlates with equatorward shifts in the PVG tropopause and hence a decrease in upper-tropospheric width. Long-term trends in the PVG tropopause over the period 1980–2017 exhibit a distinct vertical structure with poleward shifts below 340 K potential temperature, equatorward shifts between 340 and 370 K, and poleward shifts between 370 and 380 K. This consistent widening at lower levels and narrowing in the upper troposphere also exhibit considerable zonal variability with the strongest upper-tropospheric narrowing over the eastern Pacific.
Published: 2024
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2. Accelerating Lagrangian transport simulations on graphics processing units: performance optimizations of Massive-Parallel Trajectory Calculations (MPTRAC) v2.6

Author: L. Hoffmann, K. Haghighi Mood, A. Herten, M. Hrywniak, J. Kraus, J. Clemens, and M. Liu
Subjects: Geology, QE1-996.5
Abstract: Lagrangian particle dispersion models are indispensable tools for the study of atmospheric transport processes. However, Lagrangian transport simulations can become numerically expensive when large numbers of air parcels are involved. To accelerate these simulations, we made considerable efforts to port the Massive-Parallel Trajectory Calculations (MPTRAC) model to graphics processing units (GPUs). Here we discuss performance optimizations of the major bottleneck of the GPU code of MPTRAC, the advection kernel. Timeline, roofline, and memory analyses of the baseline GPU code revealed that the application is memory-bound, and performance suffers from near-random memory access patterns. By changing the data structure of the horizontal wind and vertical velocity fields of the global meteorological data driving the simulations from structure of arrays (SoAs) to array of structures (AoSs) and by introducing a sorting method for better memory alignment of the particle data, performance was greatly improved. We evaluated the performance on NVIDIA A100 GPUs of the Jülich Wizard for European Leadership Science (JUWELS) Booster module at the Jülich Supercomputing Center, Germany. For our largest test case, transport simulations with 108 particles driven by the European Centre for Medium-Range Weather Forecasts (ECMWF) ERA5 reanalysis, we found that the runtime for the full set of physics computations was reduced by 75 %, including a reduction of 85 % for the advection kernel. In addition to demonstrating the benefits of code optimization for GPUs, we show that the runtime of central processing unit (CPU-)only simulations is also improved. For our largest test case, we found a runtime reduction of 34 % for the physics computations, including a reduction of 65 % for the advection kernel. The code optimizations discussed here bring the MPTRAC model closer to applications on upcoming exascale high-performance computing systems and will also be of interest for optimizing the performance of other models using particle methods.
Published: 2024
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3. Implementation and evaluation of diabatic advection in the Lagrangian transport model MPTRAC 2.6

Author: J. Clemens, L. Hoffmann, B. Vogel, S. Grießbach, and N. Thomas
Subjects: Geology, QE1-996.5
Abstract: Diabatic transport schemes with hybrid zeta coordinates, which follow isentropes in the stratosphere, are known to greatly improve Lagrangian transport calculations compared to the kinematic approach. However, some Lagrangian transport calculations with a diabatic approach, such as the Chemical Lagrangian Transport Model of the Stratosphere (CLaMS), are not well prepared to run on modern high-performance computing (HPC) architectures. Here, we implemented and evaluated a new diabatic transport scheme in the Massive-Parallel Trajectory Calculations (MPTRAC) model. While MPTRAC can be used either with shared-memory multiprocessing on CPUs or with GPUs to offload computationally intensive calculations, making it flexible for many HPC applications, it has been limited to kinematic trajectories in pressure coordinates. The extended modelling approach now enables the use of either kinematic or diabatic vertical velocities and the coupling of different MPTRAC modules based on pressure or hybrid zeta coordinates. This study focus on the accuracy of the implementation in comparison to the CLaMS model. The evaluation of the new transport scheme in MPTRAC shows that, after 90 d of forward calculations, distributions of air parcels in the upper troposphere and lower stratosphere (UTLS) are almost identical for MPTRAC and CLaMS. No significant bias between the two Lagrangian models was found. Furthermore, after 1 d, internal uncertainties (e.g. due to interpolation or the numerical integration method) in the Lagrangian transport calculations are at least 1 order of magnitude smaller than external uncertainties (e.g. from reanalysis selection or downsampling of ERA5). Differences between trajectories using either CLaMS or MPTRAC are on the order of the combined internal uncertainties within MPTRAC. Since the largest systematic differences are caused by the reanalysis and the vertical velocity (diabatic vs. kinematic), the results support the development efforts for trajectory codes that can access the full resolution of ERA5 in combination with diabatic vertical velocities. This work is part of a larger effort to adapt Lagrangian transport in state-of-the-art models such as CLaMS and MPTRAC to current and future HPC architectures and exascale applications.
Published: 2024
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4. Evaluation of vertical transport in ERA5 and ERA-Interim reanalysis using high-altitude aircraft measurements in the Asian summer monsoon 2017

Author: B. Vogel, C. M. Volk, J. Wintel, V. Lauther, J. Clemens, J.-U. Grooß, G. Günther, L. Hoffmann, J. C. Laube, R. Müller, F. Ploeger, and F. Stroh
Subjects: Physics, QC1-999, Chemistry, QD1-999
Abstract: During the Asian monsoon season, greenhouse gases and pollution emitted near the ground are rapidly uplifted by convection up to an altitude of ∼ 13 km, with slower ascent and mixing with the stratospheric background above. Here, we address the robustness of the representation of these transport processes in different reanalysis data sets using ERA5, ERA-Interim and ERA5 1∘×1∘. This transport assessment includes the mean age of air from global three-dimensional simulations by the Lagrangian transport model CLaMS (Chemical Lagrangian Model of the Stratosphere), as well as different trajectory-based transport times and associated ascent rates compared with observation-based age of air and ascent rates of long-lived trace gases from airborne measurements during the Asian summer monsoon 2017 in Nepal. Our findings confirm that the ERA5 reanalysis yields a better representation of convection than ERA-Interim, resulting in different transport times and air mass origins at the Earth's surface. In the Asian monsoon region above 430 K, the mean age of air driven by ERA-Interim is too young, whereas the mean age of air from ERA5 1∘×1∘ is too old but somewhat closer to the observations. The mean effective ascent rates derived from ERA5 and ERA5 1∘×1∘ back trajectories are in good agreement with the observation-based mean ascent rates, unlike ERA-Interim, which is much faster above 430 K. Although a reliable CO2 reconstruction is a challenge for model simulations, we show that, up to 410 K, the CO2 reconstruction using ERA5 agrees best with high-resolution in situ aircraft CO2 measurements, indicating a better representation of Asian monsoon transport in the newest ECMWF reanalysis product, ERA5.
Published: 2024
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5. A multi-scenario Lagrangian trajectory analysis to identify source regions of the Asian tropopause aerosol layer on the Indian subcontinent in August 2016

Author: J. Clemens, B. Vogel, L. Hoffmann, S. Griessbach, N. Thomas, S. Fadnavis, R. Müller, T. Peter, and F. Ploeger
Subjects: Physics, QC1-999, Chemistry, QD1-999
Abstract: The Asian tropopause aerosol layer (ATAL) is present during the Asian summer monsoon season affecting the radiative balance of the atmosphere. However, the source regions and transport pathways of ATAL particles are still uncertain. Here, we investigate transport pathways from different regions at the model boundary layer (MBL) to the ATAL by combining two Lagrangian transport models (CLaMS, Chemical Lagrangian Model of the Stratosphere; MPTRAC, Massive-Parallel Trajectory Calculations) with balloon-borne measurements of the ATAL performed by the Compact Optical Backscatter Aerosol Detector (COBALD) above Nainital (India) in August 2016. Trajectories are initialised at the measured location of the ATAL and calculated 90 d backwards in time to investigate the relation between the measured, daily averaged, aerosol backscatter ratio and source regions at the MBL. Different simulation scenarios are performed to find differences and robust patterns when the reanalysis data (ERA5 or ERA-Interim), the trajectory model, the vertical coordinate (kinematic and diabatic approach) or the convective parameterisation are varied. The robust finding among all scenarios is that the largest continental air mass contributions originate from the Tibetan Plateau and the Indian subcontinent (mostly the Indo-Gangetic Plain), and the largest maritime air mass contributions in Asia come from the western Pacific (e.g. related to tropical cyclones). Additionally, all simulation scenarios indicate that the transport of maritime air from the tropical western Pacific to the region of the ATAL lowers the backscatter ratio (BSR) of the ATAL, while most scenarios indicate that the transport of polluted air from the Indo-Gangetic Plain increases the BSR. While the results corroborate key findings from previous ERA-Interim-based studies, they also highlight the variability in the contributions of different MBL regions to the ATAL depending on different simulation scenarios.
Published: 2024
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6. Lagrangian transport simulations using the extreme convection parameterization: an assessment for the ECMWF reanalyses

Author: L. Hoffmann, P. Konopka, J. Clemens, and B. Vogel
Subjects: Physics, QC1-999, Chemistry, QD1-999
Abstract: Atmospheric convection plays a key role in tracer transport from the planetary boundary layer to the free troposphere. Lagrangian transport simulations driven by meteorological fields from global models or reanalysis products, such as the European Centre for Medium-Range Weather Forecasts' (ECMWF's) ERA5 and ERA-Interim reanalysis, typically lack proper explicit representations of convective updrafts and downdrafts because of the limited spatiotemporal resolution of the meteorology. Lagrangian transport simulations for the troposphere can be improved by applying parameterizations to better represent the effects of unresolved convective transport in the global meteorological reanalyses. Here, we implemented and assessed the effects of the extreme convection parameterization (ECP) in the Massive-Parallel Trajectory Calculations (MPTRAC) model. The ECP is conceptually simple. It requires the convective available potential energy (CAPE) and the height of the equilibrium level (EL) as input parameters. Assuming that unresolved convective events yield well-mixed vertical columns of air, the ECP randomly redistributes the air parcels vertically between the surface and the EL if CAPE is present. We analyzed statistics of explicitly resolved and parameterized convective updrafts and found that the frequencies of strong updrafts due to the ECP, i.e., 20 K potential temperature increase over 6 h or more, increase by 2 to 3 orders of magnitude for ERA5 and 3 to 5 orders of magnitude for ERA-Interim compared to the explicitly resolved updrafts. To assess the effects of the ECP on tropospheric tracer transport, we conducted transport simulations for the artificial tracer e90, which is released globally near the surface and which has a constant e-folding lifetime of 90 d throughout the atmosphere. The e90 simulations were conducted for the year 2017 with both ERA5 and ERA-Interim. Next to sensitivity tests on the choice of the CAPE threshold, an important tuning parameter of the ECP, we suggest a modification of the ECP method, i.e., to take into account the convective inhibition (CIN) indicating the presence of warm, stable layers that prevent convective updrafts in the real atmosphere. While ERA5 has higher spatiotemporal resolution and explicitly resolves more convective updrafts than ERA-Interim, we found there is still a need for both reanalyses to apply a convection parameterization such as the ECP to better represent tracer transport from the planetary boundary layer into the free troposphere on the global scale.
Published: 2023
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7. Massive-Parallel Trajectory Calculations version 2.2 (MPTRAC-2.2): Lagrangian transport simulations on graphics processing units (GPUs)

Author: L. Hoffmann, P. F. Baumeister, Z. Cai, J. Clemens, S. Griessbach, G. Günther, Y. Heng, M. Liu, K. Haghighi Mood, O. Stein, N. Thomas, B. Vogel, X. Wu, and L. Zou
Subjects: Geology, QE1-996.5
Abstract: Lagrangian models are fundamental tools to study atmospheric transport processes and for practical applications such as dispersion modeling for anthropogenic and natural emission sources. However, conducting large-scale Lagrangian transport simulations with millions of air parcels or more can become rather numerically costly. In this study, we assessed the potential of exploiting graphics processing units (GPUs) to accelerate Lagrangian transport simulations. We ported the Massive-Parallel Trajectory Calculations (MPTRAC) model to GPUs using the open accelerator (OpenACC) programming model. The trajectory calculations conducted within the MPTRAC model were fully ported to GPUs, i.e., except for feeding in the meteorological input data and for extracting the particle output data, the code operates entirely on the GPU devices without frequent data transfers between CPU and GPU memory. Model verification, performance analyses, and scaling tests of the Message Passing Interface (MPI) – Open Multi-Processing (OpenMP) – OpenACC hybrid parallelization of MPTRAC were conducted on the Jülich Wizard for European Leadership Science (JUWELS) Booster supercomputer operated by the Jülich Supercomputing Centre, Germany. The JUWELS Booster comprises 3744 NVIDIA A100 Tensor Core GPUs, providing a peak performance of 71.0 PFlop s−1. As of June 2021, it is the most powerful supercomputer in Europe and listed among the most energy-efficient systems internationally. For large-scale simulations comprising 108 particles driven by the European Centre for Medium-Range Weather Forecasts' fifth-generation reanalysis (ERA5), the performance evaluation showed a maximum speed-up of a factor of 16 due to the utilization of GPUs compared to CPU-only runs on the JUWELS Booster. In the large-scale GPU run, about 67 % of the runtime is spent on the physics calculations, conducted on the GPUs. Another 15 % of the runtime is required for file I/O, mostly to read the large ERA5 data set from disk. Meteorological data preprocessing on the CPUs also requires about 15 % of the runtime. Although this study identified potential for further improvements of the GPU code, we consider the MPTRAC model ready for production runs on the JUWELS Booster in its present form. The GPU code provides a much faster time to solution than the CPU code, which is particularly relevant for near-real-time applications of a Lagrangian transport model.
Published: 2022
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8. Characterization of transport from the Asian summer monsoon anticyclone into the UTLS via shedding of low potential vorticity cutoffs

Author: J. Clemens, F. Ploeger, P. Konopka, R. Portmann, M. Sprenger, and H. Wernli
Subjects: Physics, QC1-999, Chemistry, QD1-999
Abstract: Air mass transport within the summertime Asian monsoon circulation provides a major source of anthropogenic pollution for the upper troposphere and lower stratosphere (UTLS). Here, we investigate the quasi-horizontal transport of air masses from the Asian summer monsoon anticyclone (ASMA) into the extratropical lower stratosphere and their chemical evolution. For that reason, we developed a method to identify and track the air masses exported from the monsoon. This method is based on the anomalously low potential vorticity (PV) of these air masses (tropospheric low PV cutoffs) compared to the lower stratosphere and uses trajectory calculations and chemical fields from the Chemical Lagrangian Model of the Stratosphere (CLaMS). The results show evidence of frequent summertime transport from the monsoon anticyclone to midlatitudes over the North Pacific, even reaching the high-latitude regions of Siberia and Alaska. Most of the low PV cutoffs related to air masses exported from the ASMA have lifetimes shorter than 1 week (about 90 %) and sizes smaller than 1 % of the Northern Hemisphere (NH) area. The chemical composition of these air masses is characterized by carbon monoxide, ozone, and water vapour mixing ratios at an intermediate range between values typical for the monsoon anticyclone and the lower stratosphere. The chemical evolution during transport within these low PV cutoffs shows a gradual change from the characteristics of the monsoon anticyclone to characteristics of the lower stratospheric background during about 1 week, indicating continuous mixing with the background atmosphere.
Published: 2022
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9. Potassium dynamics in the soil and yield formation in a long-term field experiment

Author: H.W. Scherer, H.E. Goldbach, and J. Clemens
Subjects: potassium, fertilisation, availability, yield formation, potatoes, sugar beet, winter wheat, Plant culture, SB1-1110
Abstract: The influence of an interrupted K fertilisation on different K fractions of the soil, yield formation and K uptake by different crops was investigated in a long-term field experiment on Luvisol derived from loess. Irrespective of the previous K fertilisation, the interruption of K fertilisation resulted in a sharp decline of CAL extractable K. K concentration in the saturation extract as well as HCl extractable K were reduced while K fixation capacity increased within 10 years after omitting K. Omitting K fertilisation decreased yields of sugar beet and potatoes while cereals were not affected, although K uptake of all crops reacted to the differentiated K supply to a different extent.
Published: 2003
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10. An assessment of terminology for intraspecific diversity in fishes, with a focus on 'ecotypes' and 'life histories'

Author: Benjamin J. Clemens and Carl B. Schreck
Subjects: education.field_of_study, biology, Ecotype, Ecology, Population, Reviews, Vertebrate, Review, Subspecies, biology.organism_classification, Intraspecific competition, Race (biology), Taxon, Evolutionary biology, biology.animal, Oncorhynchus, education, Ecology, Evolution, Behavior and Systematics, QH540-549.5, Nature and Landscape Conservation
Abstract: Understanding and preserving intraspecific diversity (ISD) is important for species conservation. However, ISD units do not have taxonomic standards and are not universally recognized. The terminology used to describe ISD is varied and often used ambiguously. We compared definitions of terms used to describe ISD with use in recent studies of three fish taxa: sticklebacks (Gasterosteidae), Pacific salmon and trout (Oncorhynchus spp., “PST”), and lampreys (Petromyzontiformes). Life history describes the phenotypic responses of organisms to environments and includes biological parameters that affect population growth or decline. Life‐history pathway(s) are the result of different organismal routes of development that can result in different life histories. These terms can be used to describe recognizable life‐history traits. Life history is generally used in organismal‐ and ecology‐based journals. The terms paired species/species pairs have been used to describe two different phenotypes, whereas in some species and situations a continuum of phenotypes may be expressed. Our review revealed overlapping definitions for race and subspecies, and subspecies and ecotypes. Ecotypes are genotypic adaptations to particular environments, and this term is often used in genetic‐ and evolution‐based journals. “Satellite species” is used for situations in which a parasitic lamprey yields two or more derived, nonparasitic lamprey species. Designatable Units, Evolutionary Significant Units (ESUs), and Distinct Population Segments (DPS) are used by some governments to classify ISD of vertebrate species within distinct and evolutionary significant criteria. In situations where the genetic or life‐history components of ISD are not well understood, a conservative approach would be to call them phenotypes., The terminology used to describe intraspecific diversity is varied and often used ambiguously. “Ecotype” was originally used to describe patterns in genes and ecology, and recent studies employing this term tend to report a genetic basis in ISD. By contrast, “life history” describes biological parameters that affect demography, and this term tends to be used in organismal‐ and ecology‐based journals.
Published: 2021

11. The Feasibility of Blinding Residency Programs to USMLE Step 1 Scores During GME Application, Interview, and Match Processes

Author: Richard Amini, Madhulika Banerjee, Kathy W. Smith, and Conrad J. Clemens
Subjects: Medical education, Blinding, Rank (computer programming), MEDLINE, Internship and Residency, General Medicine, Surveys and Questionnaires, Radiation oncology, Emergency Medicine, Educational Innovation, Feasibility Studies, Humans, Psychology, Child, Selection (genetic algorithm)
Abstract: Background With the recent announcement that Step 1 score reporting will soon change to pass/fail, residency programs will need to reconsider their recruitment processes. Objective We (1) evaluated the feasibility of blinding residency programs to applicants' Step 1 scores and their number of attempts throughout the recruitment process; (2) described the selection process that resulted from the blinding; and (3) reviewed if a program's initial rank list, created before scores were known, would be changed before submission for the Match. Methods During the 2018–2019 and 2019–2020 recruitment seasons, all programs at a single sponsoring institution were invited to develop selection criteria in the absence of Step 1 data, and to remain blinded to this data throughout recruitment. Participating programs were surveyed to determine factors affecting feasibility and metrics used for residency selection. Once unblinded to Step 1 scores, programs had the option to change their initial rank lists. Results Of 24 residency programs, 4 participated (17%) in the first year: emergency medicine, neurology, pediatrics, and psychiatry. The second year had the same participants, with the addition of family and community medicine and radiation oncology (n = 6, 25%). Each program was able to determine mission-specific qualities in the absence of Step 1 data. In both years, one program made changes to the final rank list. Conclusions It was feasible for programs to establish metrics for residency recruitment in the absence of Step 1 data, and most programs made no changes to final rank lists after Step 1 scores were known.
Published: 2021

12. International Triadin Knockout Syndrome Registry: The Clinical Phenotype and Treatment Outcomes of Patients with Triadin Knockout Syndrome

Author: Michael J. Silka, Lia Crotti, Julien Fauré, Dominic Abrams, Seshadri Balaji, Carlo Napolitano, Frederic Sacher, J. Martijn Bos, David J. Tester, John R. Giudicessi, Michael J. Ackerman, Vincent Probst, Mark A. Walsh, Silvia G. Priori, Daniel J. Clemens, Ram K. Rohatgi, Nathalie Roux-Buisson, Caroline Rooryck-Thambo, Peter J. Schwartz, Clemens, D, Tester, D, Giudicessi, J, Bos, J, Rohatgi, R, Abrams, D, Balaji, S, Crotti, L, Faure, J, Napolitano, C, Priori, S, Probst, V, Rooryck-Thambo, C, Roux-Buisson, N, Sacher, F, Schwartz, P, Silka, M, Walsh, M, and Ackerman, M
Subjects: business.industry, phenotype, Long QT syndrome, Treatment outcome, Null (mathematics), BIO/18 - GENETICA, General Medicine, MED/11 - MALATTIE DELL'APPARATO CARDIOVASCOLARE, 030204 cardiovascular system & hematology, medicine.disease, Bioinformatics, Phenotype, 03 medical and health sciences, 0302 clinical medicine, pediatric, Triadin, medicine, long QT syndrome, human, genetic, business, Clinical phenotype, 030217 neurology & neurosurgery
Abstract: Background: Triadin knockout syndrome (TKOS) is a rare, inherited arrhythmia syndrome caused by recessive null mutations in TRDN -encoded cardiac triadin. Based previously on 5 triadin null patients, TKOS has been characterized by extensive T-wave inversions, transient QT prolongation, and severe disease expression of exercise-induced cardiac arrest in early childhood refractory to conventional therapy. Methods: We have established the International Triadin Knockout Syndrome Registry to include patients who have genetically proven homozygous/compound heterozygous TRDN null mutations. Clinical/genetic data were collected using an online survey generated through REDCap. Results: Currently, the International Triadin Knockout Syndrome Registry includes 21 patients (11 males, average age of 18 years) from 16 families. Twenty patients (95%) presented with either cardiac arrest (15, 71%) or syncope (5, 24%) at an average age of 3 years. Mild skeletal myopathy/proximal muscle weakness was noted in 6 (29%) patients. Of the 19 surviving patients, 16 (84%) exhibit T-wave inversions, and 10 (53%) have transient QT prolongation > 480 ms. Eight of 9 patients had ventricular ectopy on exercise stress testing. Thirteen (68%) patients have received implantable defibrillators. Despite various treatment strategies, 14 (74%) patients have had recurrent breakthrough cardiac events. Conclusion: TKOS is a potentially lethal disease characterized by T-wave inversions in the precordial leads, transient QT prolongation in some, and recurrent ventricular arrhythmias at a young age despite aggressive treatment. Patients displaying this phenotype should undergo TRDN genetic testing as TKOS may be a cause for otherwise unexplained cardiac arrest in young children. As gene therapy advances, enrollment into the International Triadin Knockout Syndrome Registry is encouraged to better understand TKOS and to ready a well-characterized cohort for future TRDN gene therapy trials.
Published: 2019

13. Open-field PET: Simultaneous brain functional imaging and behavioural response measurements in freely moving small animals

Author: Gary Perkins, Kelly J. Clemens, Giancarlo Pascali, John Eisenhuth, William J. Ryder, Roger Fulton, Victor W Zhou, Andre Kyme, Genevra Hart, Kata Popovic, Bernard W. Balleine, Mahmood Akhtar, Georgios I. Angelis, Arvind Parmar, and Steven R. Meikle
Subjects: Male, Positron emission tomography, Computer science, Cognitive Neuroscience, 0299 Other Physical Sciences, Behavioral neuroscience, Imaging brain, 050105 experimental psychology, Open field, Rats, Sprague-Dawley, Awake animal imaging, 03 medical and health sciences, 0302 clinical medicine, Neuroimaging, 0903 Biomedical Engineering, In vivo, Dopamine receptor D2, medicine, 0801 Artificial Intelligence and Image Processing, Animals, 0501 psychology and cognitive sciences, Amphetamine, Receptor, Raclopride, Behavior, Animal, medicine.diagnostic_test, Functional Neuroimaging, Motion compensation, 05 social sciences, Brain, 1103 Clinical Sciences, Rats, Functional imaging, Neurology, Positron-Emission Tomography, Neuroscience, 030217 neurology & neurosurgery, medicine.drug
Abstract: A comprehensive understanding of how the brain responds to a changing environment requires techniques capable of recording functional outputs at the whole-brain level in response to external stimuli. Positron emission tomography (PET) is an exquisitely sensitive technique for imaging brain function but the need for anaesthesia to avoid motion artefacts precludes concurrent behavioural response studies. Here, we report a technique that combines motion-compensated PET with a robotically-controlled animal enclosure to enable simultaneous brain imaging and behavioural recordings in unrestrained small animals. The technique was used to measure in vivo displacement of [11C]raclopride from dopamine D2 receptors (D2R) concurrently with changes in the behaviour of awake, freely moving rats following administration of unlabelled raclopride or amphetamine. The timing and magnitude of [11C]raclopride displacement from D2R were reliably estimated and, in the case of amphetamine, these changes coincided with a marked increase in stereotyped behaviours and hyper-locomotion. The technique, therefore, allows simultaneous measurement of changes in brain function and behavioural responses to external stimuli in conscious unrestrained animals, giving rise to important applications in behavioural neuroscience.
Published: 2019

14. FoodPatternsEquivalentsIntakes By Americans 0304 1516

Author: Shanthy A Bowman, J. Clemens, Friday, James E, Schroeder, Natalia, Shimizu, Miyuki, LaComb, Randy P, and Moshfegh, Alanna J
Published: 2018
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15. Utilizing the Genome Aggregation Database, Computational Pathogenicity Prediction Tools, and Patch Clamp Heterologous Expression Studies to Demote Previously Published Type 1 Long QT Syndrome Mutations from Pathogenic to Benign

Author: Wei Zhou, Jamie D. Kapplinger, Daniel J. Clemens, Anne R. Lentino, Michael J. Ackerman, Dan Ye, and David J. Tester
Subjects: Male, 0301 basic medicine, Patch-Clamp Techniques, Romano-Ward Syndrome, In silico, Long QT syndrome, DNA Mutational Analysis, 030204 cardiovascular system & hematology, computer.software_genre, medicine.disease_cause, Genome, Article, 03 medical and health sciences, 0302 clinical medicine, Heart Conduction System, Physiology (medical), False positive paradox, medicine, Missense mutation, Humans, Genetic Predisposition to Disease, Cells, Cultured, Mutation, Database, business.industry, Computational Biology, DNA, medicine.disease, Phenotype, Romano–Ward syndrome, 030104 developmental biology, KCNQ1 Potassium Channel, Female, Cardiology and Cardiovascular Medicine, business, computer
Abstract: Background Mutations in the KCNQ1-encoded Kv7.1 potassium channel cause long QT syndrome (LQTS) type 1 (LQT1). It has been suggested that ∼10%–20% of rare LQTS case-derived variants in the literature may have been published erroneously as LQT1-causative mutations and may be "false positives." Objective The purpose of this study was to determine which previously published KCNQ1 case variants are likely false positives. Methods A list of all published, case-derived KCNQ1 missense variants (MVs) was compiled. The occurrence of each MV within the Genome Aggregation Database (gnomAD) was assessed. Eight in silico tools were used to predict each variant's pathogenicity. Case-derived variants that were either (1) too frequently found in gnomAD or (2) absent in gnomAD but predicted to be pathogenic by ≤2 tools were considered potential false positives. Three of these variants were characterized functionally using whole-cell patch clamp technique. Results Overall, there were 244 KCNQ1 case-derived MVs. Of these, 29 (12%) were seen in ≥10 individuals in gnomAD and are demotable. However, 157 of 244 MVs (64%) were absent in gnomAD. Of these, 7 (4%) were predicted to be pathogenic by ≤2 tools, 3 of which we characterized functionally. There was no significant difference in current density between heterozygous KCNQ1-F127L, -P477L, or -L619M variant-containing channels compared to KCNQ1-WT. Conclusion This study offers preliminary evidence for the demotion of 32 (13%) previously published LQT1 MVs. Of these, 29 were demoted because of their frequent sighting in gnomAD. Additionally, in silico analysis and in vitro functional studies have facilitated the demotion of 3 ultra-rare MVs (F127L, P477L, L619M).
Published: 2017

16. Implication of 4E-BP1 protein dephosphorylation and accumulation in pancreatic cancer cell death induced by combined gemcitabine and TRAIL

Author: Ricky Henry-Grant, Catherine Marboeuf, Satvinder Mudan, Androulla Elia, Michael J. Clemens, Stéphane Pyronnet, Charlotte Adiseshiah, and Rebecca J. Buckley
Subjects: 0301 basic medicine, Cancer Research, medicine.medical_treatment, Apoptosis, Cell Cycle Proteins, Deoxycytidine, TNF-Related Apoptosis-Inducing Ligand, 0302 clinical medicine, Phosphorylation, RNA, Small Interfering, Caspase, biology, lcsh:Cytology, TOR Serine-Threonine Kinases, Drug Synergism, Gene Expression Regulation, Neoplastic, Drug Combinations, medicine.anatomical_structure, Cytokine, 030220 oncology & carcinogenesis, Caspases, biological phenomena, cell phenomena, and immunity, Pancreas, medicine.drug, Signal Transduction, Programmed cell death, Immunology, Antineoplastic Agents, Time-Lapse Imaging, Article, 03 medical and health sciences, Cellular and Molecular Neuroscience, Pancreatic cancer, Cell Line, Tumor, medicine, Humans, lcsh:QH573-671, PI3K/AKT/mTOR pathway, Adaptor Proteins, Signal Transducing, business.industry, fungi, Cell Biology, Regulatory-Associated Protein of mTOR, medicine.disease, Phosphoproteins, Gemcitabine, 030104 developmental biology, Rapamycin-Insensitive Companion of mTOR Protein, Cancer research, biology.protein, business
Abstract: Pancreatic cancer cells show varying sensitivity to the anticancer effects of gemcitabine. However, as a chemotherapeutic agent, gemcitabine can cause intolerably high levels of toxicity and patients often develop resistance to the beneficial effects of this drug. Combination studies show that use of gemcitabine with the pro-apoptotic cytokine TRAIL can enhance the inhibition of survival and induction of apoptosis of pancreatic cancer cells. Additionally, following combination treatment there is a dramatic increase in the level of the hypophosphorylated form of the tumour suppressor protein 4E-BP1. This is associated with inhibition of mTOR activity, resulting from caspase-mediated cleavage of the Raptor and Rictor components of mTOR. Use of the pan-caspase inhibitor Z-VAD-FMK indicates that the increase in level of 4E-BP1 is also caspase-mediated. ShRNA-silencing of 4E-BP1 expression renders cells more resistant to cell death induced by the combination treatment. Since the levels of 4E-BP1 are relatively low in untreated pancreatic cancer cells these results suggest that combined therapy with gemcitabine and TRAIL could improve the responsiveness of tumours to treatment by elevating the expression of 4E-BP1.
Published: 2017

17. Splenomegaly, elevated alkaline phosphatase and mutations in the SRSF2/ASXL1/RUNX1 gene panel are strong adverse prognostic markers in patients with systemic mastocytosis

Author: A. Fabarius, D. Hausmann, Stefan O. Schoenberg, Wolf-Karsten Hofmann, T. Henzler, Karl Sotlar, Andreas Reiter, Juliana Schwaab, Hans-Peter Horny, Nicole Naumann, Nicholas C.P. Cross, J. Clemens, Georgia Metzgeroth, Mohamad Jawhar, and Peter Valent
Subjects: Adult, Male, Cancer Research, medicine.medical_specialty, Pathology, Gastroenterology, Organomegaly, 03 medical and health sciences, 0302 clinical medicine, Mastocytosis, Systemic, Internal medicine, medicine, Humans, Systemic mastocytosis, Survival rate, Aged, Univariate analysis, Serine-Arginine Splicing Factors, business.industry, Hazard ratio, Hematology, Middle Aged, medicine.disease, Alkaline Phosphatase, Prognosis, Confidence interval, Elevated alkaline phosphatase, Repressor Proteins, Survival Rate, Oncology, 030220 oncology & carcinogenesis, Core Binding Factor Alpha 2 Subunit, Mutation, Splenomegaly, Alkaline phosphatase, Female, medicine.symptom, business, 030215 immunology
Abstract: We evaluated the impact of clinical and molecular characteristics on overall survival (OS) in 108 patients with indolent (n=41) and advanced SM (advSM, n=67). Organomegaly was measured by magnetic resonance imaging (MRI)-based volumetry of liver and spleen. In multivariate analysis of all patients, an increased spleen volume greater than or equal to450?ml (hazard ratio [HR], 5.2; 95% confidence interval [CI], [2.1–13.0]; P=0.003) and an elevated alkaline phosphatase (AP; HR 5.0 [1.1–22.2]; P=0.02) were associated with adverse OS. The 3-year OS was 100, 77, and 39%, respectively (P
Published: 2016

18. Requirement for the eIF4E Binding Proteins for the Synergistic Down-Regulation of Protein Synthesis by Hypertonic Conditions and mTOR Inhibition

Author: Michael J. Clemens, Androulla Elia, and Simon J. Morley
Subjects: Pyridines, lcsh:Medicine, Gene Expression, Cell Cycle Proteins, Protein Synthesis, Biochemistry, mTORC2, Mice, 0302 clinical medicine, Molecular Cell Biology, Basic Cancer Research, ASK1, Eukaryotic Initiation Factors, lcsh:Science, Cells, Cultured, Cellular Stress Responses, 0303 health sciences, Multidisciplinary, TOR Serine-Threonine Kinases, Signaling Cascades, Oncology, 030220 oncology & carcinogenesis, Medicine, Phosphorylation, Research Article, Signal Transduction, Morpholines, Down-Regulation, P70-S6 Kinase 1, Biology, 03 medical and health sciences, Akt Signaling Cascade, Animals, Furans, Protein kinase A, Protein kinase B, PI3K/AKT/mTOR pathway, Adaptor Proteins, Signal Transducing, 030304 developmental biology, Saline Solution, Hypertonic, QD0415, lcsh:R, RPTOR, Proteins, Phosphoproteins, Eukaryotic Initiation Factor-4E, Pyrimidines, Protein Biosynthesis, lcsh:Q, Protein Translation, Carrier Proteins
Abstract: The protein kinase mammalian target of rapamycin (mTOR) regulates the phosphorylation and activity of several proteins that have the potential to control translation, including p70S6 kinase and the eIF4E binding proteins 4E-BP1 and 4E-BP2. In spite of this, in exponentially growing cells overall protein synthesis is often resistant to mTOR inhibitors. We report here that sensitivity of wild-type mouse embryonic fibroblasts (MEFs) to mTOR inhibitors can be greatly increased when the cells are subjected to the physiological stress imposed by hypertonic conditions. In contrast, protein synthesis in MEFs with a double knockout of 4E-BP1 and 4E-BP2 remains resistant to mTOR inhibitors under these conditions. Phosphorylation of p70S6 kinase and protein kinase B (Akt) is blocked by the mTOR inhibitor Ku0063794 equally well in both wild-type and 4E-BP knockout cells, under both normal and hypertonic conditions. The response of protein synthesis to hypertonic stress itself does not require the 4E-BPs. These data suggest that under certain stress conditions: (i) translation has a greater requirement for mTOR activity and (ii) there is an absolute requirement for the 4E-BPs for regulation by mTOR. Importantly, dephosphorylation of p70S6 kinase and Akt is not sufficient to affect protein synthesis acutely.
Published: 2013

19. Search for contact interactions and large extra dimensions in dilepton events from pp collisions at sqrt[s]=7??TeV with the ATLAS detector

Author: G. Aad, T. Abajyan, B. Abbott, J. Abdallah, S. Abdel Khalek, A. Abdelalim, O. Abdinov, R. Aben, B. Abi, M. Abolins, O. AbouZeid, H. Abramowicz, H. Abreu, B. Acharya, L. Adamczyk, D. Adams, T. Addy, J. Adelman, S. Adomeit, P. Adragna, T. Adye, S. Aefsky, J. Aguilar Saavedra, M. Agustoni, M. Aharrouche, S. Ahlen, F. Ahles, A. Ahmad, M. Ahsan, G. Aielli, T. Åkesson, G. Akimoto, A. Akimov, M. Alam, J. Albert, S. Albrand, M. Aleksa, I. Aleksandrov, F. Alessandria, C. Alexa, G. Alexander, G. Alexandre, T. Alexopoulos, M. Alhroob, M. Aliev, G. Alimonti, J. Alison, B. Allbrooke, P. Allport, S. Allwood Spiers, J. Almond, A. Aloisio, R. Alon, A. Alonso, F. Alonso, A. Altheimer, B. Alvarez Gonzalez, M. Alviggi, K. Amako, C. Amelung, V. Ammosov, S. Amor Dos Santos, A. Amorim, N. Amram, C. Anastopoulos, L. Ancu, N. Andari, T. Andeen, C. Anders, G. Anders, K. Anderson, A. Andreazza, V. Andrei, M. L. Andrieux, X. Anduaga, S. Angelidakis, P. Anger, A. Angerami, F. Anghinolfi, A. Anisenkov, N. Anjos, A. Annovi, A. Antonaki, M. Antonelli, A. Antonov, J. Antos, F. Anulli, M. Aoki, S. Aoun, L. Aperio Bella, R. Apolle, G. Arabidze, I. Aracena, Y. Arai, A. Arce, S. Arfaoui, J. F. Arguin, S. Argyropoulos, E. Arik, M. Arik, A. Armbruster, O. Arnaez, V. Arnal, C. Arnault, A. Artamonov, G. Artoni, D. Arutinov, S. Asai, S. Ask, B. Åsman, L. Asquith, K. Assamagan, A. Astbury, M. Atkinson, B. Aubert, E. Auge, K. Augsten, M. Aurousseau, G. Avolio, R. Avramidou, D. Axen, G. Azuelos, Y. Azuma, M. Baak, G. Baccaglioni, C. Bacci, A. Bach, H. Bachacou, K. Bachas, M. Backes, M. Backhaus, J. Backus Mayes, E. Badescu, P. Bagnaia, S. Bahinipati, Y. Bai, D. Bailey, T. Bain, J. Baines, O. Baker, M. Baker, S. Baker, P. Balek, E. Banas, P. Banerjee, S.w. Banerjee, D. Banfi, A. Bangert, V. Bansal, H. Bansil, L. Barak, S. Baranov, A. Barbaro Galtieri, T. Barber, E. Barberio, D. Barberis, M. Barbero, D. Bardin, T. Barillari, M. Barisonzi, T. Barklow, N. Barlow, B. Barnett, R. Barnett, A. Baroncelli, G. Barone, A. Barr, F. Barreiro, J. Barreiro Guimarães da Costa, P. Barrillon, R. Bartoldus, A. Barton, V. Bartsch, A. Basye, R. Bates, L. Batkova, J. Batley, A. Battaglia, M. Battistin, F. Bauer, H. Bawa, S. Beale, T. Beau, P. Beauchemin, R. Beccherle, P. Bechtle, H. Beck, K. Becker, S. Becker, M. Beckingham, K. Becks, A. Beddall, S. Bedikian, V. Bednyakov, C. Bee, L. Beemster, M. Begel, S. Behar Harpaz, P. Behera, M. Beimforde, C. Belanger Champagne, P. Bell, W. Bell, G. Bella, M. Bellomo, A. Belloni, O. Beloborodova, K. Belotskiy, O. Beltramello, O. Benary, D. Benchekroun, K. Bendtz, N. Benekos, Y. Benhammou, E. Benhar Noccioli, J. Benitez Garcia, D. Benjamin, M. Benoit, J. Bensinger, K. Benslama, S. Bentvelsen, D. Berge, E. Bergeaas Kuutmann, N. Berger, F. Berghaus, E. Berglund, J. Beringer, P. Bernat, R. Bernhard, C. Bernius, T. Berry, C. Bertella, F. Bertolucci, M. Besana, G. Besjes, N. Besson, S. Bethke, W. Bhimji, R. Bianchi, L. Bianchini, M. Bianco, O. Biebel, S. Bieniek, K. Bierwagen, J. Biesiada, M. Biglietti, H. Bilokon, M. Bindi, S. Binet, A. Bingul, C. Bini, C. Biscarat, B. Bittner, C. Black, K. Black, R. Blair, J. B. Blanchard, G. Blanchot, T. Blazek, I. Bloch, C. Blocker, J. Blocki, A. Blondel, W. Blum, U. Blumenschein, G. Bobbink, V. Bobrovnikov, S. Bocchetta, A. Bocci, C. Boddy, M. Boehler, J. Boek, N. Boelaert, J. Bogaerts, A. Bogdanchikov, A. Bogouch, C. Bohm, J. Bohm, V. Boisvert, T. Bold, V. Boldea, N. Bolnet, M. Bomben, M. Bona, M. Boonekamp, S. Bordoni, C. Borer, A. Borisov, G. Borissov, I. Borjanovic, M. Borri, S. Borroni, J. Bortfeldt, V. Bortolotto, K. Bos, M. Bosman, H. Boterenbrood, J. Bouchami, J. Boudreau, E. Bouhova Thacker, D. Boumediene, C. Bourdarios, N. Bousson, A. Boveia, J. Boyd, I. Boyko, I. Bozovic Jelisavcic, J. Bracinik, P. Branchini, A. Brandt, G. Brandt, O. Brandt, U. Bratzler, B. Brau, J. Brau, H. Braun, S. Brazzale, B. Brelier, J. Bremer, K. Brendlinger, R. Brenner, S. Bressler, D. Britton, F. Brochu, I. Brock, R. Brock, F. Broggi, C. Bromberg, J. Bronner, G. Brooijmans, T. Brooks, W. Brooks, G. Brown, H. Brown, P. Bruckman de Renstrom, D. Bruncko, R. Bruneliere, S. Brunet, M. Bruschi, T. Buanes, Q. Buat, F. Bucci, J. Buchanan, P. Buchholz, R. Buckingham, A. Buckley, S. Buda, I. Budagov, B. Budick, V. Büscher, L. Bugge, O. Bulekov, A. Bundock, M. Bunse, T. Buran, H. Burckhart, S. Burdin, T. Burgess, S. Burke, E. Busato, P. Bussey, C. Buszello, B. Butler, J. Butler, C. Buttar, J. Butterworth, W. Buttinger, M. Byszewski, S. Cabrera Urbán, O. Cakir, P. Calafiura, G. Calderini, P. Calfayan, R. Calkins, L. Caloba, R. Caloi, D. Calvet, S. Calvet, R. Camacho Toro, P. Camarri, D. Cameron, L. Caminada, R. Caminal Armadans, S. Campana, M. Campanelli, V. Canale, F. Canelli, A. Canepa, J. Cantero, R. Cantrill, L. Capasso, M. Capeans Garrido, I. Caprini, M. Caprini, D. Capriotti, M. Capua, R. Caputo, R. Cardarelli, T. Carli, G. Carlino, L. Carminati, B. Caron, S. Caron, E. Carquin, G. Carrillo Montoya, A. Carter, J. Carter, J. Carvalho, D. Casadei, M. Casado, M. Cascella, C. Caso, A. Castaneda Hernandez, E. Castaneda Miranda, V. Castillo Gimenez, N. Castro, G. Cataldi, P. Catastini, A. Catinaccio, J. Catmore, A. Cattai, G. Cattani, S. Caughron, V. Cavaliere, P. Cavalleri, D. Cavalli, M. Cavalli Sforza, V. Cavasinni, F. Ceradini, A. Cerqueira, A. Cerri, L. Cerrito, F. Cerutti, S. Cetin, A. Chafaq, D. Chakraborty, I. Chalupkova, K. Chan, P. Chang, B. Chapleau, J. Chapman, E. Chareyre, D. Charlton, V. Chavda, C. Chavez Barajas, S. Cheatham, S. Chekanov, S. Chekulaev, G. Chelkov, M. Chelstowska, C. Chen, H. Chen, S. Chen, X. Chen, Y. Chen, Y. Cheng, A. Cheplakov, R. Cherkaoui El Moursli, V. Chernyatin, E. Cheu, S. Cheung, L. Chevalier, G. Chiefari, L. Chikovani, J. Childers, A. Chilingarov, G. Chiodini, A. Chisholm, R. Chislett, A. Chitan, M. Chizhov, G. Choudalakis, S. Chouridou, I. Christidi, A. Christov, D. Chromek Burckhart, M. Chu, J. Chudoba, G. Ciapetti, A. Ciftci, R. Ciftci, D. Cinca, V. Cindro, C. Ciocca, A. Ciocio, M. Cirilli, P. Cirkovic, Z. Citron, M. Citterio, M. Ciubancan, A. Clark, P. Clark, R. Clarke, W. Cleland, J. Clemens, B. Clement, C. Clement, Y. Coadou, M. Cobal, A. Coccaro, J. Cochran, L. Coffey, J. Cogan, J. Coggeshall, E. Cogneras, J. Colas, S. Cole, A. Colijn, N. Collins, C. Collins Tooth, J. Collot, T. Colombo, G. Colon, G. Compostella, P. Conde Muiño, E. Coniavitis, M. Conidi, S. Consonni, V. Consorti, S. Constantinescu, C. Conta, G. Conti, F. Conventi, M. Cooke, B. Cooper, A. Cooper Sarkar, K. Copic, T. Cornelissen, M. Corradi, F. Corriveau, A. Cortes Gonzalez, G. Cortiana, G. Costa, M. Costa, D. Costanzo, D. Côté, L. Courneyea, G. Cowan, C. Cowden, B. Cox, K. Cranmer, F. Crescioli, M. Cristinziani, G. Crosetti, S. Crépé Renaudin, C. M. Cuciuc, C. Cuenca Almenar, T. Cuhadar Donszelmann, J. Cummings, M. Curatolo, C. Curtis, C. Cuthbert, P. Cwetanski, H. Czirr, P. Czodrowski, Z. Czyczula, S. D’Auria, M. D’Onofrio, A. D’Orazio, M. Da Cunha Sargedas De Sousa, C. Da Via, W. Dabrowski, A. Dafinca, T. Dai, C. Dallapiccola, M. Dam, M. Dameri, D. Damiani, H. Danielsson, V. Dao, G. Darbo, G. Darlea, J. Dassoulas, W. Davey, T. Davidek, N. Davidson, R. Davidson, E. Davies, M. Davies, O. Davignon, A. Davison, Y. Davygora, E. Dawe, I. Dawson, R. Daya Ishmukhametova, K. De, R. de Asmundis, S. De Cecco, J. de Graat, N. De Groot, P. de Jong, C. De La Taille, H. De la Torre, F. De Lorenzi, L. de Mora, L. De Nooij, D. De Pedis, A. De Salvo, U. De Sanctis, A. De Santo, J. De Vivie De Regie, G. De Zorzi, W. Dearnaley, R. Debbe, C. Debenedetti, B. Dechenaux, D. Dedovich, J. Degenhardt, J. Del Peso, T. Del Prete, T. Delemontex, M. Deliyergiyev, A. Dell’Acqua, L. Dell’Asta, M. Della Pietra, D. della Volpe, M. Delmastro, P. Delsart, C. Deluca, S. Demers, M. Demichev, B. Demirkoz, S. Denisov, D. Derendarz, J. Derkaoui, F. Derue, P. Dervan, K. Desch, E. Devetak, P. Deviveiros, A. Dewhurst, B. DeWilde, S. Dhaliwal, R. Dhullipudi, A. Di Ciaccio, L. Di Ciaccio, C. Di Donato, A. Di Girolamo, B. Di Girolamo, S. Di Luise, A. Di Mattia, B. Di Micco, R. Di Nardo, A. Di Simone, M. Diaz, E. Diehl, J. Dietrich, T. Dietzsch, S. Diglio, K. Dindar Yagci, J. Dingfelder, F. Dinut, C. Dionisi, P. Dita, S. Dita, F. Dittus, F. Djama, T. Djobava, M. do Vale, A. Do Valle Wemans, T. Doan, M. Dobbs, D. Dobos, E. Dobson, J. Dodd, C. Doglioni, T. Doherty, Y. Doi, J. Dolejsi, I. Dolenc, Z. Dolezal, B. Dolgoshein, T. Dohmae, M. Donadelli, J. Donini, J. Dopke, A. Doria, A. Dos Anjos, A. Dotti, M. Dova, A. Doxiadis, A. Doyle, N. Dressnandt, M. Dris, J. Dubbert, S. Dube, E. Duchovni, G. Duckeck, D. Duda, A. Dudarev, F. Dudziak, M. Dührssen, I. Duerdoth, L. Duflot, M. A. Dufour, L. Duguid, M. Dunford, H. Duran Yildiz, R. Duxfield, M. Dwuznik, M. Düren, W. Ebenstein, J. Ebke, S. Eckweiler, K. Edmonds, W. Edson, C. Edwards, N. Edwards, W. Ehrenfeld, T. Eifert, G. Eigen, K. Einsweiler, E. Eisenhandler, T. Ekelof, M. El Kacimi, M. Ellert, S. Elles, F. Ellinghaus, K. Ellis, N. Ellis, J. Elmsheuser, M. Elsing, D. Emeliyanov, R. Engelmann, A. Engl, B. Epp, J. Erdmann, A. Ereditato, D. Eriksson, J. Ernst, M. Ernst, J. Ernwein, D. Errede, S. Errede, E. Ertel, M. Escalier, H. Esch, C. Escobar, X. Espinal Curull, B. Esposito, F. Etienne, A. Etienvre, E. Etzion, D. Evangelakou, H. Evans, C. Fabre, R. Fakhrutdinov, S. Falciano, Y. Fang, M. Fanti, A. Farbin, A. Farilla, J. Farley, T. Farooque, S. Farrell, S. Farrington, P. Farthouat, F. Fassi, P. Fassnacht, D. Fassouliotis, B. Fatholahzadeh, A. Favareto, L. Fayard, S. Fazio, R. Febbraro, P. Federic, O. Fedin, W. Fedorko, M. Fehling Kaschek, L. Feligioni, C. Feng, E. Feng, A. Fenyuk, J. Ferencei, W. Fernando, S. Ferrag, J. Ferrando, V. Ferrara, A. Ferrari, P. Ferrari, R. Ferrari, D. Ferreira de Lima, A. Ferrer, D. Ferrere, C. Ferretti, A. Ferretto Parodi, M. Fiascaris, F. Fiedler, A. Filipčič, F. Filthaut, M. Fincke Keeler, M. Fiolhais, L. Fiorini, A. Firan, G. Fischer, M. 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Oh, S. Oh, C. Ohm, T. Ohshima, W. Okamura, H. Okawa, Y. Okumura, T. Okuyama, A. Olariu, A. Olchevski, S. Olivares Pino, M. Oliveira, D. Oliveira Damazio, E. Oliver Garcia, D. Olivito, A. Olszewski, J. Olszowska, A. Onofre, P. Onyisi, C. Oram, M. Oreglia, Y. Oren, D. Orestano, N. Orlando, I. Orlov, C. Oropeza Barrera, R. Orr, B. Osculati, R. Ospanov, C. Osuna, G. Otero y Garzon, J. Ottersbach, M. Ouchrif, E. Ouellette, F. Ould-Saada, A. Ouraou, Q. Ouyang, A. Ovcharova, M. Owen, S. Owen, V. Ozcan, N. Ozturk, A. Pacheco Page, C. Padilla Aranda, S. Pagan Griso, E. Pagani, C. Pahl, F. Paige, P. Pai, K. Pajchel, G. Palacino, C. Paleari, S. Palestini, D. Pallin, A. Palma, J. Palmer, Y. Pan, E. Panagiotopoulou, J. Panduro Vazquez, P. Pani, N. Panikashvili, S. Panitkin, D. Pantea, A. Papadeli, Th. Papadopoulou, A. Paramonov, D. Paredes Hernandez, W. Park, M. Parker, F. Parodi, J. Parson, U. Parzefall, S. Pashapour, E. Pasqualucci, S. Passaggio, A. Passeri, F. Pastore, Fr. Pastore, G. Pásztor, S. Pataraia, N. Patel, J. Pater, S. Patricelli, T. Pauly, M. Pecsy, S. Pedraza Lopez, M. Pedraza Morale, S. Peleganchuk, D. Pelikan, H. Peng, B. Penning, A. Penson, J. Penwell, M. Perantoni, K. Perez, T. Perez Cavalcanti, E. Perez Codina, M. Pérez García-Estañ, V. Perez Reale, L. Perini, H. Pernegger, R. Perrino, P. Perrodo, V. Peshekhonov, K. Peter, B. Petersen, J. Petersen, T. Petersen, E. Petit, A. Petridi, C. Petridou, E. Petrolo, F. Petrucci, D. Petschull, M. Petteni, R. Pezoa, A. Phan, P. Phillip, G. Piacquadio, A. Picazio, E. Piccaro, M. Piccinini, S. Piec, R. Piegaia, D. Pignotti, J. Pilcher, A. Pilkington, J. Pina, M. Pinamonti, A. Pinder, J. Pinfold, B. Pinto, C. Pizio, M. Plamondon, M.-A. Pleier, E. Plotnikova, A. Poblaguev, S. Poddar, F. Podlyski, L. Poggioli, D. Pohl, M. Pohl, G. Polesello, A. Policicchio, A. Polini, J. Poll, V. Polychronako, D. Pomeroy, K. Pommè, L. Pontecorvo, B. Pope, G. Popeneciu, D. Popovic, A. Poppleton, X. Portell Bueso, G. Pospelov, S. Pospisil, I. Potrap, C. Potter, G. Poulard, J. Poveda, V. Pozdnyakov, R. Prabhu, P. Pralavorio, A. Pranko, S. Prasad, R. Pravahan, S. Prell, K. Pretzl, D. Price, J. Price, L. Price, D. Prieur, M. Primavera, K. Prokofiev, F. Prokoshin, S. Protopopescu, J. Proudfoot, X. Prudent, M. Przybycien, H. Przysiezniak, S. Psoroula, E. Ptacek, E. Pueschel, J. Purdham, M. Purohit, P. Puzo, Y. Pylypchenko, J. Qian, A. Quadt, D. Quarrie, W. Quayle, F. Quinonez, M. Raa, V. Radeka, V. Radescu, P. Radloff, F. Ragusa, G. Rahal, A. Rahimi, D. Rahm, S. Rajagopalan, M. Rammensee, M. Ramme, A. Randle-Conde, K. Randrianarivony, F. Rauscher, T. Rave, M. Raymond, A. Read, D. Rebuzzi, A. Redelbach, G. Redlinger, R. Reece, K. Reeve, A. Reinsch, I. Reisinger, C. Rembser, Z. Ren, A. Renaud, M. Rescigno, S. Resconi, B. Resende, P. Reznicek, R. Rezvani, R. Richter, E. Richter-Wa, M. Ridel, M. Rijpstra, M. Rijssenbeek, A. Rimoldi, L. Rinaldi, R. Rio, I. Riu, G. Rivoltella, F. Rizatdinova, E. Rizvi, S. Robertson, A. Robichaud-Veronneau, D. Robinson, J. Robinson, A. Robson, J. Rocha de Lima, C. Roda, D. Roda Dos Santo, A. Roe, S. Roe, O. Røhne, S. Rolli, A. Romaniouk, M. Romano, G. Romeo, E. Romero Adam, N. Rompoti, L. Roo, E. Ro, S. Rosati, K. Rosbach, A. Rose, M. Rose, G. Rosenbaum, E. Rosenberg, P. Rosendahl, O. Rosenthal, L. Rosselet, V. Rossetti, E. Rossi, L. Rossi, M. Rotaru, I. Roth, J. Rothberg, D. Rousseau, C. Royon, A. Rozanov, Y. Rozen, X. Ruan, F. Rubbo, I. Rubinskiy, N. Ruckstuhl, V. Rud, C. Rudolph, G. Rudolph, F. Rühr, A. Ruiz-Martinez, L. Rumyantsev, Z. Rurikova, N. Rusakovich, A. Ruschke, J. Rutherfoord, P. Ruzicka, Y. Ryabov, M. Rybar, G. Rybkin, N. Ryder, A. Saavedra, I. Sadeh, H. Sadrozinski, R. Sadykov, F. Safai Tehrani, H. Sakamoto, G. Salamanna, A. Salamon, M. Saleem, D. Salek, D. Salihagic, A. Salnikov, J. Salt, B. Salvachua Ferrando, D. Salvatore, F. Salvatore, A. Salvucci, A. Salzburger, D. Sampsonidi, B. Samset, A. Sanchez, V. Sanchez Martinez, H. Sandaker, H. Sander, M. Sander, M. Sandhoff, T. Sandoval, C. Sandoval, R. Sandstroem, D. Sankey, A. Sansoni, C. Santamarina Rio, C. Santoni, R. Santonico, H. Santo, I. Santoyo Castillo, J. Saraiva, T. Sarangi, E. Sarkisyan-Grinbaum, B. Sarrazin, F. Sarri, G. Sartisohn, O. Sasaki, Y. Sasaki, N. Sasao, I. Satsounkevitch, G. Sauvage, E. Sauvan, J. Sauvan, P. Savard, V. Savinov, D. Savu, L. Sawyer, D. Saxon, J. Saxon, C. Sbarra, A. Sbrizzi, D. Scannicchio, M. Scarcella, J. Schaarschmidt, P. Schacht, D. Schaefer, U. Schäfer, A. Schaelicke, S. Schaepe, S. Schaetzel, A. Schaffer, D. Schaile, R. Schamberger, A. Schamov, V. Scharf, V. Schegelsky, D. Scheirich, M. Schernau, M. Scherzer, C. Schiavi, J. Schieck, M. Schioppa, S. Schlenker, E. Schmidt, K. Schmieden, C. Schmitt, S. Schmitt, B. Schneider, U. Schnoor, L. Schoeffel, A. Schoening, A. Schorlemmer, M. Schott, D. Schouten, J. Schovancova, M. Schram, C. Schroeder, N. Schroer, M. Schulten, J. Schulte, H.-C. Schultz-Coulon, H. Schulz, M. Schumacher, B. Schumm, Ph. Schune, C. Schwanenberger, A. Schwartzman, Ph. Schwegler, Ph. Schwemling, R. Schwienhorst, R. Schwierz, J. Schwindling, T. Schwindt, M. Schwoerer, F. Sciacca, G. Sciolla, W. Scott, J. Searcy, G. Sedov, E. Sedykh, S. Seidel, A. Seiden, F. Seifert, J. Seixa, G. Sekhniaidze, S. Sekula, K. Selbach, D. Seliverstov, B. Sellden, G. Seller, M. Seman, N. Semprini-Cesari, C. Serfon, L. Serin, L. Serkin, R. Seuster, H. Severini, A. Sfyrla, E. Shabalina, M. Shamim, L. Shan, J. Shank, Q. Shao, M. Shapiro, P. Shatalov, K. Shaw, D. Sherman, P. Sherwood, S. Shimizu, M. Shimojima, T. Shin, M. Shiyakova, A. Shmeleva, M. Shochet, D. Short, S. Shrestha, E. Shulga, M. Shupe, P. Sicho, A. Sidoti, F. Siegert, Dj. Sijacki, O. Silbert, J. Silva, Y. Silver, D. Silverstein, S. Silverstein, V. Simak, O. Simard, Lj. Simic, S. Simion, E. Simioni, B. Simmon, R. Simoniello, M. Simonyan, P. Sinervo, N. Sinev, V. Sipica, G. Siragusa, A. Sircar, A. Sisakyan, S. Sivoklokov, J. Sjölin, T. Sjursen, L. Skinnari, H. Skottowe, K. Skovpen, P. Skubic, M. Slater, T. Slavicek, K. Sliwa, V. Smakhtin, B. Smart, L. Smestad, S. Smirnov, Y. Smirnov, L. Smirnova, O. Smirnova, B. Smith, D. Smith, K. Smith, R. Smith, M. Smizanska, K. Smolek, A. Snesarev, S. Snow, J. Snow, S. Snyder, R. Sobie, J. Sodomka, A. Soffer, C. Solan, M. Solar, J. Solc, E. Soldatov, U. Soldevila, E. Solfaroli Camillocci, A. Solodkov, O. Solovyanov, V. Solovyev, N. Soni, V. Sopko, B. Sopko, M. Sosebee, R. Soualah, A. Soukharev, S. Spagnolo, F. Spanò, R. Spighi, G. Spigo, R. Spiwok, M. Spousta, T. Spreitzer, B. Spurlock, R. St. Deni, J. Stahlman, R. Stamen, E. Stanecka, R. Stanek, C. Stanescu, M. Stanescu-Bellu, M. Stanitzki, S. Stapne, E. Starchenko, J. Stark, P. Staroba, P. Starovoitov, R. Staszewski, A. Staude, P. Stavina, G. Steele, P. Steinbach, P. Steinberg, I. Stekl, B. Stelzer, H. Stelzer, O. Stelzer-Chilton, H. Stenzel, S. Stern, G. Stewart, J. Stilling, M. Stockton, K. Stoerig, G. Stoicea, S. Stonjek, P. Strachota, A. Stradling, A. Straessner, J. Strandberg, S. Strandberg, A. Strandlie, M. Strang, E. Strau, M. Strau, P. Strizenec, R. Ströhmer, D. Strom, J. Strong, R. Stroynowski, B. Stugu, I. Stumer, J. Stupak, P. Sturm, N. Style, D. Soh, D. Su, HS. Subramania, R. Subramaniam, A. Succurro, Y. Sugaya, C. Suhr, M. Suk, V. Sulin, S. Sultansoy, T. Sumida, X. Sun, J. Sundermann, K. Suruliz, G. Susinno, M. Sutton, Y. Suzuki, M. Svato, S. Swedish, I. Sykora, T. Sykora, J. Sánchez, D. Ta, K. Tackmann, A. Taffard, R. Tafirout, N. Taiblum, Y. Takahashi, H. Takai, R. Takashima, H. Takeda, T. Takeshita, Y. Takubo, M. Talby, A. Talyshev, M. Tamsett, K. Tan, J. Tanaka, R. Tanaka, S. Tanaka, A. Tanasijczuk, K. Tani, N. Tannoury, S. Tapprogge, D. Tardif, S. Tarem, F. Tarrade, G. Tartarelli, P. Ta, M. Tasevsky, E. Tassi, Y. Tayalati, C. Taylor, F. Taylor, G. Taylor, W. Taylor, M. Teinturier, F. Teischinger, M. Teixeira Dias Castanheira, P. Teixeira-Dia, K. Temming, H. Ten Kate, P. Teng, S. Terada, K. Terashi, J. Terron, M. Testa, R. Teuscher, J. Therhaag, T. Theveneaux-Pelzer, S. Thoma, J. Thoma, E. Thompson, P. Thompson, A. Thompson, L. Thomsen, E. Thomson, M. Thomson, W. Thong, R. Thun, F. Tian, M. Tibbett, T. Tic, V. Tikhomirov, Y. Tikhonov, S. Timoshenko, E. Tiouchichine, P. Tipton, S. Tisserant, T. Todorov, S. Todorova-Nova, B. Toggerson, J. Tojo, S. Tokár, K. Tokushuku, K. Tollefson, M. Tomoto, L. Tompkin, K. Tom, A. Tonoyan, C. Topfel, N. Topilin, E. Torrence, H. Torre, E. Torró Pastor, J. Toth, F. Touchard, D. Tovey, T. Trefzger, L. Tremblet, A. Tricoli, I. Trigger, S. Trincaz-Duvoid, M. Tripiana, N. Triplett, W. Trischuk, B. Trocmé, C. Troncon, M. Trottier-McDonald, P. True, M. Trzebinski, A. Trzupek, C. Tsaroucha, J. Tseng, M. Tsiakiri, P. Tsiareshka, D. Tsionou, G. Tsipoliti, S. Tsiskaridze, V. Tsiskaridze, E. Tskhadadze, I. Tsukerman, V. Tsulaia, J.-W. Tsung, S. Tsuno, D. Tsybychev, A. Tua, A. Tudorache, V. Tudorache, J. Tuggle, M. Turala, D. Turecek, I. Turk Cakir, E. Turlay, R. Turra, P. Tut, A. Tykhonov, M. Tylmad, M. Tyndel, G. Tzanako, K. Uchida, I. Ueda, R. Ueno, M. Ugland, M. Uhlenbrock, M. Uhrmacher, F. Ukegawa, G. Unal, A. Undru, G. Unel, Y. Unno, D. Urbaniec, P. Urquijo, G. Usai, M. Uslenghi, L. Vacavant, V. Vacek, B. Vachon, S. Vahsen, J. Valenta, S. Valentinetti, A. Valero, S. Valkar, E. Valladolid Gallego, S. Vallecorsa, J. Valls Ferrer, R. Van Berg, P. Van Der Deijl, R. van der Geer, H. van der Graaf, R. Van Der Leeuw, E. van der Poel, D. van der Ster, N. van Eldik, P. van Gemmeren, I. van Vulpen, M. Vanadia, W. Vandelli, A. Vaniachine, P. Vankov, F. Vannucci, R. Vari, E. Varne, T. Varol, D. Varoucha, A. Vartapetian, K. Varvell, V. Vassilakopoulo, F. Vazeille, T. Vazquez Schroeder, G. Vegni, J. Veillet, F. Veloso, R. Vene, S. Veneziano, A. Ventura, D. Ventura, M. Venturi, N. Venturi, V. Vercesi, M. Verducci, W. Verkerke, J. Vermeulen, A. Vest, M. Vetterli, I. Vichou, T. Vickey, O. Vickey Boeriu, G. Viehhauser, S. Viel, M. Villa, M. Villaplana Perez, E. Vilucchi, M. Vincter, E. Vinek, V. Vinogradov, M. Virchaux, J. Virzi, O. Vitell, M. Viti, I. Vivarelli, F. Vives Vaque, S. Vlacho, D. Vladoiu, M. Vlasak, A. Vogel, P. Vokac, G. Volpi, M. Volpi, G. Volpini, H. von der Schmitt, H. von Radziewski, E. von Toerne, V. Vorobel, V. Vorwerk, M. Vo, R. Vo, T. Vo, J. Vossebeld, N. Vranje, M. Vranjes Milosavljevic, V. Vrba, M. Vreeswijk, T. Vu Anh, R. Vuillermet, I. Vukotic, W. Wagner, P. Wagner, H. Wahlen, S. Wahrmund, J. Wakabayashi, S. Walch, J. Walder, R. Walker, W. Walkowiak, R. Wall, P. Waller, B. Walsh, C. Wang, H. Wang, J. Wang, R. Wang, S. Wang, T. Wang, A. Warburton, C. Ward, D. Wardrope, M. Warsinsky, A. Washbrook, C. Wasicki, I. Watanabe, P. Watkin, A. Watson, I. Watson, M. Watson, G. Watt, S. Watt, A. Waugh, B. Waugh, M. Weber, J. Webster, A. Weidberg, P. Weigell, J. Weingarten, C. Weiser, P. Well, T. Wenau, D. Wendland, Z. Weng, T. Wengler, S. Wenig, N. Werme, M. Werner, P. Werner, M. Werth, M. Wessel, J. Wetter, C. Weydert, K. Whalen, A. White, M. White, S. White, S. Whitehead, D. Whiteson, D. Whittington, F. Wicek, D. Wicke, F. Wicken, W. Wiedenmann, M. Wieler, P. Wienemann, C. Wiglesworth, L. Wiik-Fuch, P. Wijeratne, A. Wildauer, M. Wildt, I. Wilhelm, H. Wilken, J. Will, E. William, H. William, W. Willi, S. Willocq, J. Wilson, M. Wilson, A. Wilson, I. Wingerter-Seez, S. Winkelmann, F. Winklmeier, M. Wittgen, S. Wollstadt, M. Wolter, H. Wolter, W. Wong, G. Wooden, B. Wosiek, J. Wotschack, M. Woudstra, K. Wozniak, K. Wraight, M. Wright, B. Wrona, S. Wu, X. Wu, Y. Wu, E. Wulf, B. Wynne, S. Xella, M. Xiao, S. Xie, C. Xu, D. Xu, L. Xu, B. Yabsley, S. Yacoob, M. Yamada, H. Yamaguchi, A. Yamamoto, K. Yamamoto, S. Yamamoto, T. Yamamura, T. Yamanaka, T. Yamazaki, Y. Yamazaki, Z. Yan, H. Yang, U. Yang, Y. Yang, Z. Yang, S. Yanush, L. Yao, Y. Yao, Y. Yasu, G. Ybeles Smit, J. Ye, S. Ye, M. Yilmaz, R. Yoosoofmiya, K. Yorita, R. Yoshida, K. Yoshihara, C. Young, S. Youssef, D. Yu, J. Yu, L. Yuan, A. Yurkewicz, B. Zabinski, R. Zaidan, A. Zaitsev, Z. Zajacova, L. Zanello, D. Zanzi, A. Zaytsev, C. Zeitnitz, M. Zeman, A. Zemla, C. Zendler, O. Zenin, T. Ženiš, Z. Zinono, D. Zerwa, G. Zevi della Porta, D. Zhang, H. Zhang, J. Zhang, X. Zhang, Z. Zhang, L. Zhao, Z. Zhao, A. Zhemchugov, J. Zhong, B. Zhou, N. Zhou, Y. Zhou, C. Zhu, H. Zhu, J. Zhu, Y. Zhu, X. Zhuang, V. Zhuravlov, A. Zibell, D. Zieminska, N. Zimin, R. Zimmermann, S. Zimmermann, M. Ziolkowski, R. Zitoun, L. Živković, V. Zmouchko, G. Zobernig, A. Zoccoli, M. zur Nedden, V. Zutshi, and L. Zwalinski
Subjects: HADRON-HADRON COLLISIONS, High Energy Physics::Experiment, NEW PHYSICS
Abstract: A search for nonresonant new phenomena, originating from either contact interactions or large extra spatial dimensions, has been carried out using events with two isolated electrons or muons. These events, produced at the LHC in proton-proton collisions at √s=7 TeV, were recorded by the ATLAS detector. The data sample, collected throughout 2011, corresponds to an integrated luminosity of 4.9 and 5.0 fb-1 in the e+e- and μ+μ- channels, respectively. No significant deviations from the Standard Model expectation are observed. Using a Bayesian approach, 95% confidence level lower limits ranging from 9.0 to 13.9 TeV are placed on the energy scale of ℓℓqq contact interactions in the left-left isoscalar model. Lower limits ranging from 2.4 to 3.9 TeV are also set on the string scale in large extra dimension models. After combining these limits with results from a similar search in the diphoton channel, slightly more stringent limits are obtained.
Published: 2013

20. Long-Term Effects of Chronic Oral Ritalin Administration on Cognitive and Neural Development in Adolescent Wistar Kyoto Rats

Author: Ann K. Goodchild, Jennifer L. Cornish, Natasha N. Kumar, Kelly J. Clemens, Margery C. Pardey, and Judi Homewood
Subjects: medicine.medical_specialty, Infralimbic cortex, impulsivity, methylphenidate, Impulsivity, chronic administration, Article, lcsh:RC321-571, adolescent, tyrosine hydroxylase, prefrontal cortex, impulsive choice, Internal medicine, mental disorders, medicine, Attention deficit hyperactivity disorder, Effects of sleep deprivation on cognitive performance, Prefrontal cortex, Psychiatry, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, Methylphenidate, General Neuroscience, Extinction (psychology), medicine.disease, medicine.anatomical_structure, Endocrinology, Catecholamine, medicine.symptom, Psychology, medicine.drug
Abstract: The diagnosis of Attention Deficit Hyperactivity Disorder (ADHD) often results in chronic treatment with psychostimulants such as methylphenidate (MPH, Ritalin®). With increases in misdiagnosis of ADHD, children may be inappropriately exposed to chronic psychostimulant treatment during development. The aim of this study was to assess the effect of chronic Ritalin treatment on cognitive and neural development in misdiagnosed "normal" (Wistar Kyoto, WKY) rats and in Spontaneously Hypertensive Rats (SHR), a model of ADHD. Adolescent male animals were treated for four weeks with oral Ritalin® (2 × 2 mg/kg/day) or distilled water (dH2O). The effect of chronic treatment on delayed reinforcement tasks (DRT) and tyrosine hydroxylase immunoreactivity (TH-ir) in the prefrontal cortex was assessed. Two weeks following chronic treatment, WKY rats previously exposed to MPH chose the delayed reinforcer significantly less than the dH2O treated controls in both the DRT and extinction task. MPH treatment did not significantly alter cognitive performance in the SHR. TH-ir in the infralimbic cortex was significantly altered by age and behavioural experience in WKY and SHR, however this effect was not evident in WKY rats treated with MPH. These results suggest that chronic treatment with MPH throughout adolescence in "normal" WKY rats increased impulsive choice and altered catecholamine development when compared to vehicle controls.
Published: 2012
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21. Survival of Migrating Salmon Smolts in Large Rivers With and Without Dams

Author: Aswea D. Porter, David Welch, Carl B. Schreck, Shaun Clements, R. Scott McKinley, Erin L. Rechisky, Michael C. Melnychuk, Benjamin J. Clemens, and Carl J. Walters
Subjects: Chinook wind, Canada, Northwestern United States, QH301-705.5, Endangered species, Adaptation, Biological, Biology, General Biochemistry, Genetics and Molecular Biology, Rivers, Hydroelectricity, Salmon, Animals, Telemetry, Biology (General), Hydropower, Ecosystem, geography, geography.geographical_feature_category, General Immunology and Microbiology, Ecology, business.industry, General Neuroscience, Oceanic climate, Estuary, biology.organism_classification, Fishery, Freshwater fish, Synopsis, Animal Migration, General Agricultural and Biological Sciences, business, Pacific decadal oscillation, Research Article, Biotechnology, Environmental Monitoring
Abstract: The mortality of salmon smolts during their migration out of freshwater and into the ocean has been difficult to measure. In the Columbia River, which has an extensive network of hydroelectric dams, the decline in abundance of adult salmon returning from the ocean since the late 1970s has been ascribed in large measure to the presence of the dams, although the completion of the hydropower system occurred at the same time as large-scale shifts in ocean climate, as measured by climate indices such as the Pacific Decadal Oscillation. We measured the survival of salmon smolts during their migration to sea using elements of the large-scale acoustic telemetry system, the Pacific Ocean Shelf Tracking (POST) array. Survival measurements using acoustic tags were comparable to those obtained independently using the Passive Integrated Transponder (PIT) tag system, which is operational at Columbia and Snake River dams. Because the technology underlying the POST array works in both freshwater and the ocean, it is therefore possible to extend the measurement of survival to large rivers lacking dams, such as the Fraser, and to also extend the measurement of survival to the lower Columbia River and estuary, where there are no dams. Of particular note, survival during the downstream migration of at least some endangered Columbia and Snake River Chinook and steelhead stocks appears to be as high or higher than that of the same species migrating out of the Fraser River in Canada, which lacks dams. Equally surprising, smolt survival during migration through the hydrosystem, when scaled by either the time or distance migrated, is higher than in the lower Columbia River and estuary where dams are absent. Our results raise important questions regarding the factors that are preventing the recovery of salmon stocks in the Columbia and the future health of stocks in the Fraser River., Author Summary Miniature electronic technologies now allow researchers to track a salmon's migration from its birthplace in a river's headwaters in the Rocky Mountains to the North Pacific, opening a window on the mysteries of migration and survival. Surprisingly, outward migrating salmon (smolts) have similar survival during migration down dammed and undammed rivers, challenging widely held notions about factors affecting salmon abundance. Elements of the large-scale POST (Pacific Ocean Shelf Tracking) acoustic telemetry array revealed the migrations. Although salmon smolt survival to the Pacific Ocean was comparable in both the dammed Columbia and undammed Fraser rivers, it was higher in the Columbia once distance or travel time was taken into account—and higher within the hydropower system than below the dammed section. There is not yet enough evidence to determine whether (1) the Fraser has a problem that reduces salmon survival to that of a heavily dammed river or (2) factors other than dams play a larger, unsuspected role in salmon survival. Wherever future research leads on those questions, the new fish tagging technology has demonstrated itself as a useful tool for obtaining objective scientific data with important value in a number of public policy arenas., Electronic tagging of two species of salmon smolts reveals similar survival rates during migration down the dammed Columbia and undammed Fraser Rivers, challenging popular notions about factors affecting salmon abundance.
Published: 2008

22. Activation of p53 stimulates proteasome-dependent truncation of eIF4E-binding protein 1 (4E-BP1).

Author: Constantina Constantinou, Androulla Elia, and Michael J. Clemens
Subjects: PROTEIN binding, POLYPEPTIDES, MESSENGER RNA, PHOSPHORYLATION
Abstract: Background information. The translational inhibitor protein 4E-BP1 [eIF4E (eukaryotic initiation factor 4E)-binding protein 1] regulates the availability of polypeptide chain initiation factor eIF4E for protein synthesis. Initiation factor eIF4E binds the 5′ cap structure present on all cellular mRNAs. Its ability to associate with initiation factors eIF4G and eIF4A, forming the eIF4F complex, brings the mRNA to the 43S complex during the initiation of translation. Binding of eIF4E to eIF4G is inhibited in a competitive manner by 4E-BP1. Phosphorylation of 4E-BP1 decreases the affinity of this protein for eIF4E, thus favouring the binding of eIF4G and enhancing translation. We have previously shown that induction or activation of the tumour suppressor protein p53 rapidly leads to 4E-BP1 dephosphorylation, resulting in sequestration of eIF4E, decreased formation of the eIF4F complex and inhibition of protein synthesis.Results. We now report that activation of p53 also results in modification of 4E-BP1 to a truncated form. Unlike full-length 4E-BP1, which is reversibly phosphorylated at multiple sites, the truncated protein is almost completely unphosphorylated. Moreover, the latter interacts with eIF4E in preference to full-length 4E-BP1. Inhibitor studies indicate that the p53-induced cleavage of 4E-BP1 is mediated by the proteasome and is blocked by conditions that inhibit the dephosphorylation of full-length 4E-BP1. Measurements of the turnover of 4E-BP1 indicate that the truncated form is much more stable than the full-length protein.Conclusions. The results suggest a model in which proteasome activity gives rise to a stable, hypophosphorylated and truncated form of 4E-BP1, which may exert a long-term inhibitory effect on the availability of eIF4E, thus contributing to the inhibition of protein synthesis and the growth-inhibitory and pro-apoptotic effects of p53. [ABSTRACT FROM AUTHOR]
Published: 2008

23. Testretest reliability of the multifocal electroretinogram and Humphrey visual fields in patients with retinitis pigmentosa.

Author: William Seiple, Colleen J. Clemens, Vivienne C. Greenstein, Ronald E. Carr, and Karen Holopigian
Subjects: RETINAL degeneration, ANALYSIS of variance, HONESTY, VISUAL fields
Abstract: Abstract We examined the reliability of Humphrey visual field thresholds and multifocal electroretinogram (mfERG) amplitudes and timing in a group of patients with Retinitis Pigmentosa (RP). Eight patients with RP and seven control subjects were tested five times: at baseline (visit #0), at three weekly follow-up visits (visits #1#3), and at three months (visit #4). For the Humphrey thresholds, differences between dB values on repeat visits were obtained. Differences between log values on repeat visits were calculated for mfERG amplitude and implicit time. We used the standard deviations of these difference scores as a measure of reliability and the means of the difference scores as a measure of progression. We found that the majority of the patients repeat data were more variable than that of the control subjects for both the Humphrey and mfERG. We found no single factor that predicted the magnitude, or the variance, of the SD of differences scores for the patients. We recommend that each patients reliability be assessed individually. Ultimately, the choice of an outcome measure must be guided by its reliability, as well as its ability to assess the visual function of interest. [ABSTRACT FROM AUTHOR]
Published: 2004

24. Interferons and Apoptosis.

Author: Michael J. Clemens
Published: 2003

25. Accurate and stable numerical Hartree-Fock calculations for atoms. I. The 1 s2 ground state of H−, He, Li+, and Be++.

Author: Roothaan, C. J. Clemens and Soukup, George A.
Published: 1979
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26. The Common Sense Theology of Bishop White Sydney A. Temple Jr.

Author: Kolb, J. Clemens
Published: 1947

27. Differential requirements for caspase-8 activity in the mechanism of phosphorylation of eIF2α, cleavage of eIF4GI and signaling events associated with the inhibition of protein synthesis in apoptotic Jurkat T cells

Author: Ian W. Jeffrey, Virginia M. Pain, Simon J. Morley, Martin Bushell, and Michael J. Clemens
Subjects: Eukaryotic Initiation Factor-2, Biophysics, P70-S6 Kinase 1, Apoptosis, Biology, Biochemistry, Jurkat cells, Jurkat Cells, eIF-2 Kinase, 03 medical and health sciences, Peptide Initiation Factors, Structural Biology, Genetics, Humans, fas Receptor, Phosphorylation, Eukaryotic initiation factor 2α, Protein kinase A, Molecular Biology, 030304 developmental biology, Caspase 8, 0303 health sciences, Cleavage stimulation factor, Hydrolysis, Ribosomal Protein S6 Kinases, 030302 biochemistry & molecular biology, Autophosphorylation, Eukaryotic initiation factor 4G, Cell Biology, Fas receptor, Molecular biology, Caspase 9, Cell biology, Enzyme Activation, Caspases, Protein Biosynthesis, Signal transduction, Eukaryotic Initiation Factor-4G, Protein synthesis, Caspase-8, Signal Transduction
Abstract: Previously we have reported that induction of apoptosis in Jurkat cells results in an inhibition of overall protein synthesis with the selective and rapid cleavage of eukaryotic initiation factor (eIF) 4GI. For the cleavage of eIF4GI, caspase-3 activity is both necessary and sufficient in vivo, in a process which does not require signaling through the p38 MAP kinase pathway. We now show that activation of the Fas/CD95 receptor promotes an early, transient increase in the level of eIF2alpha phosphorylation, which is temporally correlated with the onset of the inhibition of translation. This is associated with a modest increase in the autophosphorylation of the protein kinase activated by double-stranded RNA. Using a Jurkat cell line that is deficient in caspase-8 and resistant to anti-Fas-induced apoptosis, we show that whilst the cleavage of eIF4GI is caspase-8-dependent, the enhancement of eIF2alpha phosphorylation does not require caspase-8 activity and occurs prior to the cleavage of eIF4GI. In addition, activation of the Fas/CD95 receptor results in the caspase-8-dependent dephosphorylation and degradation of p70(S6K), the enhanced binding of 4E-BP1 to eIF4E, and, at later times, the cleavage of eIF2alpha. These data suggest that apoptosis impinges upon the activity of several polypeptides which are central to the regulation of protein synthesis and that multiple signaling pathways are involved in vivo.
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28. Regulation of protein synthesis by inducible wild-type p53 in human lung carcinoma cells

Author: Vivienne J. Tilleray, Constantina Constantinou, and Michael J. Clemens
Subjects: p53, Lung Neoplasms, Mutant, Biophysics, Apoptosis, Cell Cycle Proteins, Biology, Biochemistry, Retinoblastoma-like protein 1, Structural Biology, Cell Line, Tumor, Eukaryotic initiation factor, Translational regulation, Genetics, Protein biosynthesis, Humans, Initiation factor, Growth control, Molecular Biology, Adaptor Proteins, Signal Transducing, Inducible gene expression, EIF4E, Wild type, Cell Biology, Phosphoproteins, Molecular biology, Eukaryotic Initiation Factor-4E, Gene Expression Regulation, Doxycycline, Protein Biosynthesis, Tumor Suppressor Protein p53, Polypeptide chain initiation
Abstract: Activation of an over-expressed mutant form of the tumour suppressor protein p53 has been shown to inhibit protein synthesis. To determine whether this effect is due only to high level expression or the mutant nature of the protein, we have used a doxycycline-inducible lung carcinoma cell line capable of expressing wild-type p53. We now show that levels of wild-type p53 similar to those expressed endogenously also inhibit protein synthesis. The mechanism involves dephosphorylation and accumulation of the translational inhibitor 4E-BP1, and increased association of 4E-BP1 with initiation factor eIF4E. The inhibition of translation is not a consequence of p53-mediated apoptosis.
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29. In Vivo Effects of the Epstein–Barr Virus Small RNA EBER-1 on Protein Synthesis and Cell Growth Regulation

Author: Ken Laing, Michael J. Clemens, Volker Matys, Vivienne J. Tilleray, Androulla Elia, B E Souberbielle, and Ian W. Jeffrey
Subjects: Herpesvirus 4, Human, malignant transformation, protein synthesis, viruses, Biology, growth regulation, Cell Line, Malignant transformation, Epstein–Barr virus, Mice, eIF-2 Kinase, 03 medical and health sciences, 0302 clinical medicine, Neoplasms, Virology, hemic and lymphatic diseases, fibroblasts, Protein biosynthesis, Animals, Humans, Cell Line, Transformed, 030304 developmental biology, Regulation of gene expression, 0303 health sciences, Reporter gene, HEK 293 cells, RNA, virus diseases, protein kinase R, Transfection, Cell Transformation, Viral, Protein kinase R, Molecular biology, 3. Good health, Gene Expression Regulation, transfection, EBER-1 RNA, Protein Biosynthesis, 030220 oncology & carcinogenesis, tumourigenesis, RNA, Viral, Cell Division
Abstract: Recent studies have suggested a role for the Epstein–Barr virus-encoded RNA EBER-1 in malignant transformation. EBER-1 inhibits the activity of the protein kinase PKR, an inhibitor of protein synthesis with tumour suppressor properties. In human 293 cells and murine embryonic fibroblasts, transient expression of EBER-1 promoted total protein synthesis and enhanced the expression of cotransfected reporter genes. However reporter gene expression was stimulated equally well in cells from control and PKR knockout mice. NIH 3T3 cells stably expressing EBER-1 exhibited a greatly increased frequency of colony formation in soft agar, and protein synthesis in these cells was relatively resistant to inhibition by the calcium ionophore A23187. Nevertheless clones containing a high concentration of EBER-1 were not invariably tumourigenic. We conclude that EBER-1 can enhance protein synthesis by a PKR-independent mechanism and that, although this RNA may contribute to the oncogenic potential of Epstein–Barr virus, its expression is not always sufficient for malignant transformation.
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30. The role of soluble protein factors in the translational control of protein synthesis in eukaryotic cells

Author: Michael J. Clemens and Virginia M. Pain
Subjects: Reticulocytes, Cell division, Xenopus, Guinea Pigs, Biophysics, Mitosis, Biology, Biochemistry, Amino Acyl-tRNA Synthetases, Mice, Cytosol, Ribonucleases, Peptide Initiation Factors, Structural Biology, Translational regulation, Genetics, Protein biosynthesis, Animals, Myxomycetes, RNA, Messenger, Cycloheximide, Carcinoma, Ehrlich Tumor, Molecular Biology, Temperature, Proteins, RNA, Cell Biology, EIF4A1, Plants, Peptide Elongation Factors, Rats, EIF4EBP1, Polyribosomes, Protein Biosynthesis, Microsomes, Liver, Microsome, Rabbits, Ribosomes, Cell Division
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31. Met-tRNAfMet Binding to 40S Ribosomal Subunits: A Site for the Regulation of Initiation of Protein Synthesis by Hemin

Author: Hannah Rahamimoff, Michael J. Clemens, Irving M. London, and Edgar C. Henshaw
Subjects: Reticulocytes, Plasma protein binding, Heme, Sulfur Radioisotopes, Ribosome, Chromatography, DEAE-Cellulose, chemistry.chemical_compound, Methionine, Reticulocyte, RNA, Transfer, Leucine, medicine, Protein biosynthesis, Centrifugation, Density Gradient, Animals, Eukaryotic Small Ribosomal Subunit, Globin, Carbon Radioisotopes, Peptide Chain Initiation, Translational, Multidisciplinary, Chemistry, Blood Proteins, Chromatography, Ion Exchange, Molecular biology, Globins, Rats, Molecular Weight, A-site, medicine.anatomical_structure, Biochemistry, Protein Biosynthesis, Hemin, Biological Sciences: Biochemistry, Rabbits, Ribosomes, Protein Binding
Abstract: On incubation of reticulocyte lysates at 30° in the absence of added hemin, protein synthesis declines sharply within 4-6 min, due to the action of a translational inhibitor. Partially purified preparations of this inhibitor, in concentrations that inhibit protein synthesis in the lysate, cause reduced binding of Met-tRNA f Met to derived 40S ribosomal subunits in a ribosomal-salt-wash-dependent assay system. Neither the association of salt wash proteins with the subunits nor the level of Met-tRNA f Met bound in preformed 40S complexes is reduced by the inhibitor. No Met-tRNA f Met deacylase activity could be detected in the inhibitor preparation. Protein synthesis in reticulocyte lysates lacking added hemin or containing exogenous inhibitor is maintained by addition of small amounts of an initiation preparation factor, “F-MP,” which may be involved in the binding of Met-tRNA f Met to 40S subunits. This binding constitutes a site for control of protein synthesis by hemin in reticulocytes.
Published: 1974

32. Interferon-induced inhibition of protein synthesis in L-cell extracts: an ATP-dependent step in the activation of an inhibitor by double-stranded RNA

Author: Michael J. Clemens, Ian M. Kerr, and Walden K. Roberts
Subjects: viruses, Cell, Biology, Inhibitory postsynaptic potential, Viral Proteins, Adenosine Triphosphate, Cytosol, L Cells, Interferon, medicine, Protein biosynthesis, Bacteriophages, RNA, Messenger, Encephalomyocarditis virus, Diminution, Multidisciplinary, Cell-Free System, fungi, RNA, Translation (biology), Molecular biology, RNA silencing, Kinetics, Poliovirus, medicine.anatomical_structure, Biochemistry, Protein Biosynthesis, RNA, Viral, Interferons, medicine.drug, Research Article
Abstract: The translation of encephalomyocarditis virion RNA in extracts from interferon-treated L-cells is inhibited by the addition of double-stranded RNA (dsRNA) at 400 ng/ml. A similar inhibition in response to dsRNA is seen in control cell extracts supplemented with small amounts of a postribosomal supernatant fraction from interferon-treated cells (interferon cell sap): Neither interferon cell sap nor dsRNA alone is inhibitory in control systems. The inhibition is much reduced if translation is carried out at low ATP concentrations.Conversely, the inhibitory capacity of the interferon cell sap is increased 100-fold if it is preincubated with dsRNA and ATP prior to its addition to the protein-synthesizing system. After this preincubation all detectable dsRNA can be removed without any diminution of the inhibitory activity of the cell sap. These results are compatible with a two-step model for the inhibition in which a pre-inhibitor is activated by dsRNA, the activated inhibitor then interacting with the protein synthesis system to inhibit translation.
Published: 1976

33. Stimulation of incorporation of precursors into protein and ribonucleic acid of rat liver slices by bovine growth hormone in vitro

Author: A Korner and M J Clemens
Subjects: Orotic acid, Stimulation, In Vitro Techniques, Biochemistry, Leucine, Protein biosynthesis, medicine, Animals, Bovine somatotropin, Amino Acids, Molecular Biology, chemistry.chemical_classification, Orotic Acid, Chemistry, RNA, Cell Biology, Molecular biology, In vitro, Amino acid, Rats, Liver, Growth Hormone, Protein Biosynthesis, medicine.drug, Research Article
Published: 1969

34. Interferons: Mechanisms of action and role in cancer therapy Edited by D. Crowther; Springer-Verlag; Berlin, Heidelberg, New York, 1991; 63 pages. DM 72.00. ISBN 3-540-54302-3

Author: Michael J. Clemens
Subjects: Psychoanalysis, Action (philosophy), Structural Biology, Philosophy, Genetics, Biophysics, Cancer therapy, Cell Biology, Molecular Biology, Biochemistry
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35. Methods in enzymology, volumes 200 and 201: Protein phosphorylation parts A and B Edited by T. Hunter and B.M. Sefton; Academic Press; San Diego, 1991; Volume 200: xxxiv + 763 pages. $95.00; Volume 201: xxxii + 547 pages. $69.00

Author: Michael J. Clemens
Subjects: Polymer science, Structural Biology, media_common.quotation_subject, Genetics, Biophysics, Protein phosphorylation, Cell Biology, Art, Molecular Biology, Biochemistry, Volume (compression), media_common
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36. Polyfunctional cytokines: IL-6 and LIF (Ciba Foundation Symposium 167) D. Metcalf (chairman), John Wiley; Chichester, 1992; x + 279 pages. £ 42.50. ISBN 0-471-93439-9

Author: Michael J. Clemens
Subjects: Structural Biology, Philosophy, Genetics, Biophysics, Foundation (engineering), Cell Biology, Molecular Biology, Biochemistry, Humanities
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37. Species diversity in the new lamprey genus Occidentis, formerly classified as western North American 'Lampetra'.

Author: Kellie J Carim, Grace Auringer, Margaret F Docker, Claude B Renaud, Benjamin J Clemens, Monica R Blanchard, Christina Parker, and Michael K Young
Subjects: Medicine, Science
Abstract: Accurate taxonomy is fundamental to the study and conservation of biodiversity. Because of their morphological similarities, most brook and river lampreys in western North America have been placed in the genus Lampetra along with lampreys from Eurasia and eastern North America. However, molecular-based phylogenetic studies dating back several decades indicate that lampreys from Pacific drainages are genetically distinct from Atlantic Lampetra. Reviewing previous phylogenetic analysis of two mitochondrial and two nuclear genes for Northern Hemisphere lampreys, we assign these western North American brook and river lampreys to a new genus, Occidentis. To assess species diversity within Occidentis, we performed a species delimitation analysis using all publicly available cytochrome b sequences of the genus. Similar to previous studies, O. ayresii and O. richardsoni were not reciprocally monophyletic and are best categorized as life history variants of a single species. In addition to O. pacifica, O. hubbsi, and the diverse O. ayresii species complex, as many as seven undescribed candidate species from Oregon and California were identified, supporting results from previous studies with more geographically limited datasets. One specimen from Paynes Creek, California, was identified as a candidate species, although this single individual showed minimal interspecific divergence (1.34%) with O. hubbsi. Further genetic assessment along with information on morphology and phylogeography is needed to determine whether the variation observed between groups of candidate species represents distinct species or divergent lineages within a species complex. Additional sampling will inform whether there are additional species not currently represented in this dataset. Thus, the number of species formally recognized under Occidentis is subject to change with new information. Systematic assessment of the distribution and phylogenetic complexity within Occidentis will enhance our understanding of its evolutionary history and taxonomic diversity, which will guide efforts to conserve the biodiversity of lampreys.
Published: 2024
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38. Editorial: The neurology and neurobiology of neonatal abstinence syndrome

Author: Kelly J. Clemens, Ju-Lee Oei, and Lauren L. Jantzie
Subjects: neonatal brain, phenobarbital, methadone, sex differences, opioid, buprenorphine, Pediatrics, RJ1-570
Published: 2023
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39. SARS-CoV-2 spike protein-mediated cardiomyocyte fusion may contribute to increased arrhythmic risk in COVID-19.

Author: Daniel J Clemens, Dan Ye, Wei Zhou, C S John Kim, David R Pease, Chanakha K Navaratnarajah, Alison Barkhymer, David J Tester, Timothy J Nelson, Roberto Cattaneo, Jay W Schneider, and Michael J Ackerman
Subjects: Medicine, Science
Abstract: BackgroundSARS-CoV-2-mediated COVID-19 may cause sudden cardiac death (SCD). Factors contributing to this increased risk of potentially fatal arrhythmias include thrombosis, exaggerated immune response, and treatment with QT-prolonging drugs. However, the intrinsic arrhythmic potential of direct SARS-CoV-2 infection of the heart remains unknown.ObjectiveTo assess the cellular and electrophysiological effects of direct SARS-CoV-2 infection of the heart using human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs).MethodshiPSC-CMs were transfected with recombinant SARS-CoV-2 spike protein (CoV-2 S) or CoV-2 S fused to a modified Emerald fluorescence protein (CoV-2 S-mEm). Cell morphology was visualized using immunofluorescence microscopy. Action potential duration (APD) and cellular arrhythmias were measured by whole cell patch-clamp. Calcium handling was assessed using the Fluo-4 Ca2+ indicator.ResultsTransfection of hiPSC-CMs with CoV-2 S-mEm produced multinucleated giant cells (syncytia) displaying increased cellular capacitance (75±7 pF, n = 10 vs. 26±3 pF, n = 10; PConclusionThe SARS-CoV-2 spike protein can directly perturb both the cardiomyocyte's repolarization reserve and intracellular calcium handling that may confer the intrinsic, mechanistic substrate for the increased risk of SCD observed during this COVID-19 pandemic.
Published: 2023
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40. 501 ASSOCIATIONS BETWEEN UROLOGIC CHRONIC PELVIC PAIN SYMPTOM FLARES AND QUALITY OF LIFE, HEALTH-CARE SEEKING ACTIVITY, AND ILLNESS IMPACT: FINDINGS FROM THE MULTIDISCIPLINARY APPROACH TO THE STUDY OF CHRONIC PELVIC PAIN SYMPTOM PATTERNS STUDY

Author: S Sutcliffe, C Newcomb, C Bradley, J Clemens, B Erickson, P Gupta, H Lai, B Naliboff, E Strachan, and A Stephens-Shields
Subjects: Diseases of the genitourinary system. Urology, RC870-923
Published: 2022
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41. A role for a novel natural antisense-BDNF in the maintenance of nicotine-seeking

Author: Neil A. Youngson, Matthew R. Castino, Angela Stuart, Kelly A. Kershaw, Nathan M. Holmes, Eilish C. Heffernan, Paul D. Waters, Kevin V. Morris, and Kelly J. Clemens
Subjects: Infralimbic, Non-coding RNA, Addiction, Rat, Extinction, Antisense, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract: Brain derived neurotrophic factor (BDNF) is critical for the extinction of drug-seeking. Expression of the Bdnf gene is highly epigenetically regulated, including via interactions with non-coding RNA. Here we investigate whether a long non-coding RNA antisense to Bdnf exon IV is involved in extinction of drug-seeking. Strand-specific RNA sequencing confirmed the presence of a novel long non-coding RNA antisense to exon IV of the Bdnf gene in the ventromedial prefrontal cortex of adult male rats (Bdnf-IV-AS). Bdnf-IV-AS expression was validated using strand-specific reverse transcription and quantitative polymerase chain reaction following acquisition, extinction or abstinence from intravenous nicotine self-administration. Expression of Bdnf-IV-AS was elevated following intravenous nicotine self-administration but not experimenter-administered nicotine. Elevated Bdnf-IV-AS persisted across abstinence and to a greater extent following extinction training, suggesting an interaction between Bdnf-IV-AS, nicotine and extinction learning. A functional role of the Bdnf-IV-AS in extinction of nicotine-seeking was established by infusing gapmer oligonucleotides into the infralimbic cortex prior to extinction and testing for the effect of these infusions on reinstatement and reacquisition of nicotine-seeking. Knockdown of the Bdnf-IV-AS across cue-extinction, but not abstinence, significantly attenuated nicotine-primed reinstatement of nicotine-seeking. Bdnf-IV-AS accumulates in the infralimbic cortex across self-administration training, interferes with the inhibitory learning that underpins extinction of drug-seeking, and predisposes animals to drug relapse.
Published: 2022
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42. Social isolation enhances cued-reinstatement of sucrose and nicotine seeking, but this is reversed by a return to social housing

Author: Natalie A. Mastrogiovanni, Alice K. Wheeler, and Kelly J. Clemens
Subjects: Medicine, Science
Abstract: Abstract Physical or perceived (i.e. loneliness) social isolation is increasing in Western cultures. Unfortunately, social isolation is associated with a range of negative physical and mental health outcomes, including increased incidence of obesity and smoking. Here we monitored the impact of social isolation on a range of physical measures, and then tested whether social isolation in adult rats changes how reward-related stimuli motivate sucrose- or nicotine-seeking. Socially isolated rats showed elevated baseline CORT, gained significantly less weight across the study, were more active in response to a novel or familiar environment. Isolated rats also acquired nose-poking for a food pellet more rapidly, and showed increased susceptibility to cue-, but not reward-induced reinstatement. Notably, these effects are partially mitigated by a return to group housing, suggesting that they are not necessarily permanent, and that a return to a social setting can quickly reverse any deficits or changes associated with social isolation. This study advances our understanding of altered reward-processing in socially isolated individuals and reiterates the importance of socialisation in the treatment of disorders such as overeating and addiction.
Published: 2021
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43. A review of potential conservation and fisheries benefits of breaching four dams in the Lower Snake River (Washington, USA)

Author: Adam J. Storch, Howard A. Schaller, Charles E. Petrosky, Robert L. Vadas, Jr., Benjamin J. Clemens, Gary Sprague, Norman Mercado-Silva, Brett Roper, Michael J. Parsley, Edward Bowles, Robert M. Hughes, and Jay A. Hesse
Subjects: Bull trout, Impoundment, Pacific lamprey, Salmon, Steelhead, White sturgeon, Environmental sciences, GE1-350, Biology (General), QH301-705.5
Abstract: Abundances of important and imperiled fishes of the Snake River Basin continue to decline. We assessed the rationale for breaching the four lower Snake River Basin dams to prevent complete loss of these fishes, and to maximize their likelihood of recovery. We summarize the science surrounding Sockeye Salmon (Oncorhynchus nerka), Chinook Salmon (O. tshawytscha), steelhead (O. mykiss), Bull Trout (Salvelinus confluentus), White Sturgeon (Acipenser transmontanus), and Pacific Lamprey (Entosphenus tridentatus). From this, we drew ten conclusions: (1) development of the Columbia River System (including the Snake River Basin) has converted mainstem rivers into reservoirs, altering fish behavior and survival; (2) most populations currently record their lowest abundance; (3) the Columbia River System dams reduce productivity of diadromous fishes in the highest-quality spawning grounds that could buffer against future climate dynamics; (4) past actions have done little to reduce impacts or precipitate recovery; (5) the Columbia River System constrains survival and productivity of salmon, steelhead and Bull Trout; (6) Snake River Basin salmon and steelhead remain at high extinction risk; (7) eliminating migration impediments and improving mainstem habitats are essential for maintaining genetic diversity and improving Bull Trout persistence; (8) the lower Snake River Basin dams preclude passage of adult White Sturgeon, constraining gene flow and recruitment; (9) the lower Snake River Basin dams impede dramatically passage of adult and juvenile Pacific Lamprey, and (10) Snake River Basin Pacific Lamprey is at high risk of extirpation. Breaching the four lower Snake River Basin dams is an action likely to prevent extirpation and extinction of these fishes. Lessons from the Columbia River System can inform conservation in other impounded rivers.
Published: 2022
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44. Utility of extracellular vesicles as a potential biological indicator of physiological resilience during military operational stress

Author: Meaghan E. Beckner, William R. Conkright, Amrita Sahu, Qi Mi, Zachary J. Clemens, Brian J. Martin, Shawn D. Flanagan, Fabio Ferrarelli, Fabrisia Ambrosio, and Bradley C. Nindl
Subjects: decision trees, extracellular vesicles, machine learning, occupational stress, resilience, Physiology, QP1-981
Abstract: Abstract Extracellular vesicles (EVs) transport biological content between cells to mediate physiological processes. The association between EVs and resilience, the ability to cope with stress, is unknown. Using unbiased machine learning approaches, we aimed to identify a biological profile of resilience. Twenty servicemen (27.8 ± 5.9 years) completed the Connor Davidson Resilience (CD‐RISC) questionnaire and were exposed to daily physical and cognitive exertion with 48‐hr sleep and caloric restriction. Blood samples from baseline and the second day of stress were analyzed for neuroendocrine biomarkers impacted by military stress. EVs were isolated from plasma and stained with antibodies associated with exosomes (CD63), microvesicles (VAMP3), and apoptotic bodies (THSD1). Individuals were separated into high (n = 10, CD‐RISC > 90) and low (n = 10, CD‐RISC
Published: 2022
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45. Les laits tropicaux. Etude de la composition chimique et des variations de composition des laits de vaches au Mali

Author: R. Rivière and J. Clémensat
Subjects: Zébu, Lait de vache, Composition chimique, Matière grasse du lait, Teneur en matière sèche, Bovin n'dama, Animal culture, SF1-1100
Abstract: Les auteurs poursuivent l'étude du lait des vaches de races N'Dama et Zébu du Centre de Recherches Zootechniques de Sotuba-Bamako. Après avoir envisagé, dans un article précédent, les variations des taux de matières protéiques totales, de la caséine et du rapport caséine/protéines totales, ils considérent celles de la densité, de la matière grasse et des différents extraits secs: - extrait sec, extrait sec dégraissé, extrait sec calculé et extrait sec dégraissé rectifié
Published: 1966
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46. Les possibilités fourragères de Digitaria umfolozi en zone soudanienne : Problèmes posés par l'étude systématique d'une plante fourragère

Author: G. Boudet, R. Rivière, J. Clémensat, Jean Pagot, and J.F. Lahore
Subjects: Digitaria, Valeur nutritive, Composition chimique, Pratique culturale, Conduite des herbages, Taux de charge, Animal culture, SF1-1100
Abstract: cf. fichier PDF de l'article.
Published: 1961
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47. Les laits tropicaux : étude de la composition chimique et des variations de composition des laits de vaches au Mali

Author: R. Rivière and J. Clémensat
Subjects: Facteur du milieu, Lait, Bovin, Zébu, Composition chimique, Variation saisonnière, Animal culture, SF1-1100
Abstract: Disposant, au Centre de Recherches Zootechniques de Sotuba-Bamako, d'un important cheptel bovin de races N'Dama et Zébu, les auteurs ont entrepris l'étude systématique du lait de ces animaux et en particulier des variations de sa composition en fonction de l'espèce, de la saison et de la date du vêlage. Cette étude comprendra deux parties: 1) Composition et variations des laits moyens; 2) Variations de la Composition des laits individuels. Le milieu et les conditions d'entretien des animaux sont décrits. Les méthodes d'analyse employées sont précisées. Les principaux constituants du lait sont considérés ainsi que les différents rapports ou constantes classiques calculés à partir de ces éléments. Une analyse statistique est faite des résultats qui sont comparés aux données fournies par d'autres auteurs en pays tropicaux
Published: 1964
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48. Dispelling misperceptions of native lampreys (Entosphenus and Lampetra spp.) in the Pacific northwest (USA)

Author: Benjamin J. Clemens and Christina J. Wang
Subjects: conservation, education, fishes, native, outreach, sea lamprey, Ecology, QH540-549.5, General. Including nature conservation, geographical distribution, QH1-199.5
Abstract: Abstract Native lampreys continue to be misunderstood by some citizens in the Pacific Northwest (PNW; USA). This misunderstanding is caused by persistent misperceptions reinforced in media and exacerbated by a long‐running (mid‐1900s to present) and pervasive outreach campaign on the control of the invasive sea lamprey (Petromyzon marinus) in the Laurentian Great Lakes, Lake Champlain and the Finger Lakes of New York. The use of outreach to encourage conservation of native lampreys in the PNW has been comparatively recent. Along with other native non‐salmonid fishes, lampreys were perceived by Euro‐American settlers as “undesirable”, “coarse” or “trash” fish that parasitized desirable trouts and salmon (Oncorhynchus spp.) and competed with them for environmental resources. These concerns have been magnified by the seemingly physical and ecological similarities between native and invasive sea lampreys. To dispel the misperceptions of native lampreys, we recommend a multi‐prong approach that: sharpens the specificity of outreach materials on sea lamprey control; develops outreach media that distinguishes invasive and native lampreys, includes recognition of the multiple ecosystem benefits that native lampreys offer, and includes hands‐on, place‐based learning led by or in collaboration with local tribes that can provide cultural context, and employs a broad outreach campaign to facilitate conservation of native lampreys.
Published: 2021
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49. The dual orexin receptor antagonist TCS1102 does not affect reinstatement of nicotine-seeking.

Author: Shaun Yon-Seng Khoo, Gavan P McNally, and Kelly J Clemens
Subjects: Medicine, Science
Abstract: The orexin/hypocretin system is important for appetitive motivation towards multiple drugs of abuse, including nicotine. Both OX1 and OX2 receptors individually have been shown to influence nicotine self-administration and reinstatement. Due to the increasing clinical use of dual orexin receptor antagonists in the treatment of disorders such as insomnia, we examined whether a dual orexin receptor antagonist may also be effective in reducing nicotine seeking. We tested the effect of intracerebroventricular (i.c.v.) administration of the potent and selective dual orexin receptor antagonist TCS1102 on orexin-A-induced food self-administration, nicotine self-administration and reinstatement of nicotine-seeking in rats. Our results show that 30 μg of TCS1102 i.c.v. abolishes orexin-A-induced increases in food self-administration but does not reduce nicotine self-administration. Neither i.c.v. 10 μg nor 30 μg of TCS1102 reduced compound reinstatement after short-term (15 days) self-administration nicotine, but 30 μg transiently reduced cue/nicotine compound reinstatement after chronic self-administration (29 days). These results indicate that TCS1102 has no substantial effect on motivation for nicotine seeking following chronic self-administration and no effect after shorter periods of intake. Orexin receptor antagonists may therefore have little clinical utility against nicotine addiction.
Published: 2017
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50. Vaccination greatly reduces disease, disability, death and inequity worldwide

Author: FE Andre, R Booy, HL Bock, J Clemens, SK Datta, TJ John, BW Lee, S Lolekha, H Peltola, TA Ruff, M Santosham, and HJ Schmitt
Subjects: Public aspects of medicine, RA1-1270
Abstract: In low-income countries, infectious diseases still account for a large proportion of deaths, highlighting health inequities largely caused by economic differences. Vaccination can cut health-care costs and reduce these inequities. Disease control, elimination or eradication can save billions of US dollars for communities and countries. Vaccines have lowered the incidence of hepatocellular carcinoma and will control cervical cancer. Travellers can be protected against "exotic" diseases by appropriate vaccination. Vaccines are considered indispensable against bioterrorism. They can combat resistance to antibiotics in some pathogens. Noncommunicable diseases, such as ischaemic heart disease, could also be reduced by influenza vaccination. Immunization programmes have improved the primary care infrastructure in developing countries, lowered mortality in childhood and empowered women to better plan their families, with consequent health, social and economic benefits. Vaccination helps economic growth everywhere, because of lower morbidity and mortality. The annual return on investment in vaccination has been calculated to be between 12% and 18%. Vaccination leads to increased life expectancy. Long healthy lives are now recognized as a prerequisite for wealth, and wealth promotes health. Vaccines are thus efficient tools to reduce disparities in wealth and inequities in health.
Published: 2008

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