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Purpose: The aim of this work is to evaluate a new eight‐channel transceiver (TxRx) coaxial dipole array for imaging of the human head at 9.4T developed to improve specific absorption rate (SAR) performance, and provide for a more compact and robust alternative to the state‐of‐the art dipole arrays. Methods: First, the geometry of a single coaxial element was optimized to minimize peak SAR and sensitivity to the load variation. Next, a multi‐tissue voxel model was used to numerically simulate a TxRx array coil that consisted of eight coaxial dipoles with the optimal configuration. Finally, we compared the developed array to other human head dipole arrays. Results of numerical simulations were verified on a bench and in the scanner including in vivo measurements on a healthy volunteer. Results: The developed eight‐element coaxial dipole TxRx array coil showed up to 1.1times higher SAR‐efficiency than a similar in geometry folded‐end and fractionated dipole array while maintaining whole brain coverage and low sensitivity of the resonance frequency to variation in the head size. Conclusion: As a proof of concept, we developed and constructed a prototype of a 9.4T (400 MHz) human head array consisting of eight TxRx coaxial dipoles. The developed array improved SAR‐efficiency and provided for a more compact and robust alternative to the folded‐end dipole design. To the best of our knowledge, this is the first example of using coaxial dipoles for human head MRI at ultra‐high field. [ABSTRACT FROM AUTHOR]

The U.S. Department of Agriculture‐Agricultural Research Service's (ARS) Experimental Watershed Network grew from Dust Bowl era efforts of the Soil Conservation Service in the mid‐1930s with the establishment of small experimental watersheds. In the 1950s, five watershed research centers with intensively instrumented watersheds at the scale of 100 to 700 km2 were established. Primary network research objectives were to quantify on‐site and downstream effects of conservation practices and develop rainfall‐runoff relationships for design of water conservation structures. With passage of the Clean Water Act in 1972, research objectives have evolved to add a variety of observations relevant to the water quality issues. Many of the watersheds within the network have served, and continue to serve, as core validation sites for satellite sensors. As a result of the network's long history and intensive monitoring, coupled with mission‐driven research, a deep knowledge base of watershed processes has been developed. This has led to the extensive development and validation of numerous watershed models that are in widespread use today. The visionary investments in building and maintaining this network and associated scientific investigations for more than half a century have not only resulted in numerous high‐impact research accomplishments but also a wide array of accomplishments that directly benefit society. The ARS Experimental Watersheds formed the core of the Conservation Effects Assessment Project (CEAP) as well as the recently established Long‐Term Agroecosystem Research (LTAR) network. LTAR will expand the mission of the ARS Watersheds Network to include agricultural intensification, maintaining or improving ecosystem services while enhancing rural prosperity. Plain Language Summary: Understanding how watersheds respond to precipitation, agricultural management, and other land use changes is critical to maintaining clean water, viable food production, and predicting flood hazards and soil loss from erosion. To understand watershed responses and processes, the Soil Conservation Service, followed by the USDA‐Agricultural Research Service, established experimental watersheds across the United States. These watersheds were instrumented with equipment to make detailed measurements of weather and watershed response. Experiments were designed to observe how runoff, erosion, and water quality might change with changing agricultural practices to change agricultural practices and observe how runoff, erosion, and water quality would change. From these experiments, predictive computer models were developed and tested with data from the watersheds. The watershed observations, the process knowledge developed, and associated research and models have resulted in numerous societal benefits. Billions of dollars of conservation measures and drainage infrastructure investment were guided by these models and methods. The ARS Experimental Watersheds formed the core of the recently established Long‐Term Agroecosystem Research (LTAR) network. LTAR will expand the mission of the ARS Watershed Network to include producing more food on the same amout of land, maintaining or improving ecosystem services (clean water and air, healthy soils, etc.) while enhancing rural prosperity. Key Points: Agricultural Research Service's Experimental Watersheds and associated mission‐driven research have operated for over half a centuryHigh‐resolution watershed observations and experimentation have produced a deep watershed process knowledge and databaseThe research network has been critical to developing and validating numerous watershed models and management methods, resulting in extensive societal benefits [ABSTRACT FROM AUTHOR]

New petrographic and microstructural observations, mineral equilibria modelling and U/Pb (monazite) geochronological studies were carried out to investigate the relationships between deformation and metamorphism across the Rehamna massif (Moroccan Variscan belt). In this area, typical Barrovian (muscovite to staurolite) zones developed in Cambrian to Carboniferous metasedimentary rocks that are distributed around a dome-like structure. First assemblages are characterized by the presence of locally preserved andalusite, followed by prograde evolution culminating at 6 kbar and 620 °C in the structurally deepest staurolite zone rocks. This Barrovian sequence was subsequently uplifted to supracrustal levels, heterogeneously reworked at greenschist facies conditions, which was followed locally by static growth of andalusite, indicating heating to 2.5-4 kbar and 530-570 °C. The 206Pb/238U monazite age of 298.3 ± 4.1 Ma is interpreted as minimum age of peak metamorphic conditions, whereas the ages of 275.8 ± 1.7 Ma and 277.0 ± 1.1 Ma date decompression and heating at low pressure, in agreement with previous dating of Permian granitoids intruding the Rehamna massif. The prograde metamorphism occurred during thickening and associated horizontal flow in the deeper crust (S1 horizontal schistosity). The horizontally disposed metamorphic zones were subsequently uplifted by a regional scale antiform during ongoing N-S compression. The re-heating of the massif follows late massive E-W shortening, refolding and retrograde shearing of all previous fabrics coevally with regionally important intrusions of Permian granitoids. We argue that metamorphic evolution of the Rehamna massif occurred several hundred kilometres from the convergent plate boundaries in the interior of continental Gondwanan plate. The tectonometamorphic history of the Rehamna massif is put into Palaeozoic plate tectonic perspective and Late Carboniferous reactivation of (Devonian)-Early Carboniferous basins formed during stretching of the north Gondwana margin and formation of the Palaeotethys Ocean. The inherited heat budget of these magma-rich basins plays a role in the preferential location of this intracontinental orogen. It is shown that rapid transition from lithospheric stretching to compression is characterized by specific HT type of Barrovian metamorphism, which markedly differs from similar Barrovian sequences along Palaeozoic plate boundaries reported from Variscan Europe. [ABSTRACT FROM AUTHOR]

A spatially distributed representation of basin hydrology and transport processes in hydrologic models facilitates the identification of critical source areas and the placement of management and conservation measures. Floodplains are critical landscape features that differ from neighbouring uplands in terms of their hydrological processes and functions. Accordingly, an important step in watershed modelling is the representation of floodplain and upland areas within a watershed. The aim of this study is (1) to evaluate four floodplain-upland delineation methods that use readily available topographic data (topographic wetness index, slope position, uniform flood stage, and variable flood stage) with regard to their suitability for hydrological models and (2) to introduce an evaluation scheme for the delineated landscape units. The methods are tested in three U.S. watersheds ranging in size from 334 to 629 km2 with different climatic, hydrological, and geomorphological characteristics. Evaluation of the landscape delineation methods includes visual comparisons, error matrices (i.e. cross-tabulations of delineated vs reference data), and geometric accuracy metrics. Reference data were obtained from the Soil Survey Geographic (SSURGO) database and Federal Emergency Management Agency (FEMA) flood maps. Results suggest that the slope position and the variable flood stage method work very well in all three watersheds. Overall percentages of floodplain and upland areas allocated correctly were obtained by comparing delineated and reference data. Values range from 83 to 93% for the slope position and from 80 to 95% for the variable flood stage method. Future studies will incorporate these two floodplain-upland delineation methods into the subwatershed-based hydrologic model Soil and Water Assessment Tool (SWAT) to improve the representation of hydrological processes within floodplain and upland areas. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Integrated river basin models should provide a spatially distributed representation of basin hydrology and transport processes to allow for spatially implementing specific management and conservation measures. To accomplish this, the Soil and Water Assessment Tool (SWAT) was modified by integrating a landscape routing model to simulate water flow across discretized routing units. This paper presents a grid-based version of the SWAT landscape model that has been developed to enhance the spatial representation of hydrology and transport processes. The modified model uses a new flow separation index that considers topographic features and soil properties to capture channel and landscape flow processes related to specific landscape positions. The resulting model is spatially fully distributed and includes surface, lateral and groundwater fluxes in each grid cell of the watershed. Furthermore, it more closely represents the spatially heterogeneous distributed flow and transport processes in a watershed. The model was calibrated and validated for the Little River Watershed (LRW) near Tifton, Georgia (USA). Water balance simulations as well as the spatial distribution of surface runoff, subsurface flow and evapotranspiration are examined. Model results indicate that groundwater flow is the dominant landscape process in the LRW. Results are promising, and satisfactory output was obtained with the presented grid-based SWAT landscape model. Nash-Sutcliffe model efficiencies for daily stream flow were 0.59 and 0.63 for calibration and validation periods, and the model reasonably simulates the impact of the landscape position on surface runoff, subsurface flow and evapotranspiration. Additional revision of the model will likely be necessary to adequately represent temporal variations of transport and flow processes in a watershed. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Thalamic stimulation and thalamotomy for treatment of tremor due to Parkinson's disease, essential tremor, and multiple sclerosis were compared in a randomized trial. The symptomatic and functional outcome was studied after 5 years of follow-up. Sixty-eight patients were treated (45 Parkinson's disease, 13 essential tremor, 10 multiple sclerosis) by thalamotomy (n = 34) or thalamic stimulation (n = 34). After 5 years, 48 patients were available for follow-up. The primary outcome measure was change in functional status measured by the Frenchay Activities Index (FAI), scores ranging from 0 to 60. Secondary outcome measures were tremor severity, frequency of complications, and patients' assessment of the outcome. The mean difference in FAI scores between thalamic stimulation and thalamotomy was 4.4 (95% CI: 1.1-7.7) after 6 months, 3.3 (95% CI: −0.03-6.6) after 2 years and 4.0 (95% CI: 0.3-7.7) after 5 years in favor of stimulation. Tremor suppression was equally effective after both procedures, and stable in Parkinson patients. In ET and multiple sclerosis, a diminished effect of stimulation was observed in half of the patients. There were six stimulation equipment-related complications, but neurological side effects of surgery were higher after thalamotomy. Subjective outcome-assessment by the patients was more favorable in the stimulation group. © 2008 Movement Disorder Society. [ABSTRACT FROM AUTHOR]

This article discusses the effects of tillage and variable rainfall intensity on soil erosion, runoff and carbon losses in the coastal plains of Georgia. The authors simulated rainfall on conventional till and strip-till cotton crops. They found that strip till decreased runoff and sediment and carbon losses but strip it increased soil organic carbon while maintaining infiltration. Under variable rainfall intensity events, the maximum runoff, soil loss, and carbon losses were higher than constant rainfall intensity events.

The U.S. Department of Agriculture Agricultural Research Service Southeast Watershed Research Laboratory (SEWRL) initiated a watershed research program at the Little River Experimental Watershed in 1967. Continuous rainfall measurement across the watershed began at that time. Forty-six precipitation gauges and three climate stations are currently in operation. Soil moisture measurements were added to 29 of the rainfall sites from 2001 to 2006. The research quantifies critical information related to long-term and seasonal climatic relationships, hydrologic budgets for the region, water quality studies, and natural resource planning. Rainfall data from the network have been used to evaluate storm characteristics, climatic patterns, and long-term averages for the region. Soil moisture data have been used to examine large-scale patterns across the region and for comparison to remotely sensed data. All data are available on the SEWRL anonymous ftp site (ftp://www.tiftonars.org/). [ABSTRACT FROM AUTHOR]

A water quality sampling program was initiated in 1974 by the U.S. Department of Agriculture Agricultural Research Service on the 334 km2 Little River Experimental Watershed (LREW) near Tifton in south Georgia to monitor the effects of changing land use and agricultural practices over time and to support development of simulation models capable of predicting future impacts of agricultural land use and management changes. Stream samples were taken on a weekly or more frequent basis and were analyzed for chloride, ammonium nitrogen, nitrate plus nitrite nitrogen, total kjeldahl nitrogen, total phosphorus, and dissolved molybdate reactive phosphorus. Monitoring began in 1974 on the entire watershed and four nested subwatersheds, ranging in size from 16.7 to 114.9 km2, and continues until present. Partial records of 7, 10, and 19 years exist for three additional subwatersheds. Suspended solids data are available for all eight subwatersheds for 1974-1978 and 1979-1981, three subwatersheds for 1982-1986, and all eight subwatersheds again beginning in the year 2000. The concentration and associated load data are being published on the LREW database anonymous ftp site (ftp://www.tiftonars.org/). [ABSTRACT FROM AUTHOR]

The Little River Experimental Watershed is located in the headwaters of the Upper Suwannee River basin and is one of twelve national benchmark watersheds participating in the U.S. Department of Agriculture Conservation Effects Assessment Project-Watershed Assessment Studies. A geographic database has been established to include topography, land use, hydrology, soil distribution, watershed boundaries, and site locations for all weirs, rain gauges, soil moisture sites, and climate stations. These data provide the foundation for integrating point-based measurements with landscape attributes. Each spatial layer can be accessed individually for use within a geographic information system. The watershed boundary layer will serve as the base map, projected into universal transverse Mercator coordinates (zone 17), using NAD83 as the datum and GRS80 as the ellipsoid. Data may be accessed via ftp://www.tiftonars.org/. [ABSTRACT FROM AUTHOR]

The U.S. Department of Agriculture Agricultural Research Service Southeast Watershed Research Laboratory (SEWRL) initiated a hydrologic research program on the Little River Experimental Watershed in south-central Georgia, United States, in 1967. The primary intent of the program was to develop an improved understanding of basic hydrologic and water quality processes on Coastal Plain watersheds and to evaluate the effects of agricultural management practices on the region's natural resources and environment. Long-term (up to 37 years), research-quality streamflow data have been collected for up to eight flow measurement sites within the Gulf-Atlantic Coastal Plain physiographic region, an important agricultural production area in the southeastern United States. Forty-six precipitation gauges and three climate stations are currently in operation to collect data in support of the hydrologic network. Over the past 20 years, sediment and agrichemical concentrations in streamflow have also been monitored to permit evaluation of the impacts of agriculture on regional surface and groundwater quality. Along with the hydrologic and water quality data, geographic spatial data layers for terrain, soils, geology, vegetation, and land management have also been developed. These databases, described in five accompanying data reports, can be accessed via an ftp site supported by the SEWRL (ftp://www.tiftonars.org/). [ABSTRACT FROM AUTHOR]

The U.S. Department of Agriculture Agricultural Research Service Southeast Watershed Research Laboratory (SEWRL) initiated a hydrologic research program on the Little River Experimental Watershed (LREW) in 1967. Long-term (up to 37 years) research quality streamflow data are currently available for up to eight flow measurement sites within the Gulf-Atlantic Coastal Plain physiographic region. The LREW stream discharge research program provides fundamental data for research into hydrologic processes, precipitation-runoff relationships, hydrograph characteristics, water yield, and interactive effects of climate, vegetation, soils, and land use for low-gradient Coastal Plain streams. All data are available on the SEWRL anonymous ftp site (ftp://www.tiftonars.org/). [ABSTRACT FROM AUTHOR]

The article focuses on research which was conducted in South Florida's Miami Dade agricultural area, which is located between two protected natural areas, the Biscayne and Everglades National Parks. The research was conducted in an effort to understand water quality interactions between agricultural land use and the shallow regional aquifer, and involved a 4-ha square field containing 0.9 ha of corn surrounded by fallow land. Researchers found that fertilization, masked by soil/water/plant-delayed processes, had no discernible effect on groundwater nitrate levels.

This article compares natural and simulated rainfall rates and their effect on soil nutrient losses on strip tillage and conventional tillage. According to the authors, no significant differences in total losses were evident for phosphorus and nitrogen in unfiltered samples from either rainfall intensity pattern. For filtered samples, the total mass losses of soluble phosphorus and nitrogen were highest for strip tillage at a constant rate of rainfall and lowest for conventional tillage under a variable rate of rainfall. They conclude that constant intensity rainfall simulations may over estimate the amount of dissolved nutrients lost to the environment in runoff from cropping systems in loamy sand soils.

The significance and role of major shear zones are paramount to understanding continental deformation and the exhumation of deep crustal levels. LA-ICPMS U–Pb dating of monazites, combined with Rb–Sr analyses of biotites, from an anatectic metapelite from Greater Kabylia (Algeria) highlights the history of shear zone development and the subsequent exhumation of deep crustal levels in the internal zones of the Maghrebides. Monazites give an age of 275.4 ± 4.1 Ma (2 σ) dating the thermal peak coeval with anatexis. This age is identical to those recorded in other crystalline terranes from south-easternmost Europe (i.e. South Alpine and Austro-Alpine domains) that suffered crustal thinning during the continental rifting predating the Tethys opening. Rb–Sr analyses of biotites yield a cooling age of 23.7 ± 1.1 Ma related to the exhumation of the buried Variscan crust during the Miocene as an extrusive slice, roughly coeval with the emplacement of nappes, and shortly followed by lithospheric extension leading to the opening of the Alboran sea. [ABSTRACT FROM AUTHOR]

High-pressure (HP) metabasites from the Sancti Spiritus dome (Escambray massif, Central Cuba) have been studied in order to better understand the origin and evolution of the Northern Caribbean boundary plate during the Cretaceous, in a global subduction context. Geochemical and petrological studies of these eclogites reveal two groups with contrasting origins and pre-subduction metamorphic histories. Eclogites collected from exotic blocks within serpentinite (mélange zone) originated from a N-MORB type protolith, do not record pre-eclogitic metamorphic history. Conversely eclogites intercalated in Jurassic metasedimentary rocks (non-mélange zone) have a calc-alkaline arc-like origin and yield evidence for a pre-subduction metamorphic event in the amphibolite facies. However, all the studied Escambray eclogites underwent the same eclogitic peak (around 600 °C at 16 kbar), and followed a cold thermal gradient during their exhumation (estimated at around 13.5 °C km−1), which can suggest that this exhumation was coeval with subduction. Concordant geochronological data (Rb/Sr and Ar/Ar) support that the main exhumation of HP/LT rocks from the Sancti Spiritus dome occurred at 70 Ma by top to SW thrusting. The retrograde trajectory of these rocks suggests that the north-east subduction of the Farallon plate continued after 70 Ma. The set-off to the exhumation can be correlated with the beginning of the collision between the Bahamas platform and the Cretaceous island arc that induced a change of the subduction kinematics. The contrasting origin and ante-subduction history of the analysed samples imply that the Escambray massif consists of different geological units that evolved in different environments before their amalgamation during exhumation to form the present unit III of the massif. [ABSTRACT FROM AUTHOR]

Describes a case involving a patient who developed severe temporal lobe radiation injury five years after irradiation for a rhinopharyngeal carcinoma. Extensive involvement of microcirculation found after post-mortem; Radiaton effects on vessels.

Discusses the abstract of the research 'Nasal drug delivery to the cerebrospinal fluid: Transport of a lipophilic compound,' submitted to the Dutch Society for Clinical Pharmacology & Biopharmacy on April 19, 2002.

The transcription factor GATA2 has a pivotal role in haematopoiesis. Heterozygous germline GATA2 mutations result in a syndrome characterized by immunodeficiency, bone marrow failure and predispositions to myelodysplastic syndrome (MDS) and acute myeloid leukaemia. Clinical symptoms in these patients are diverse and mechanisms driving GATA2-related phenotypes are largely unknown. To explore the impact of GATA2 haploinsufficiency on haematopoiesis, we generated a zebrafish model carrying a heterozygous mutation of gata2b (gata2b +/- ), an orthologue of GATA2. Morphological analysis revealed myeloid and erythroid dysplasia in gata2b +/- kidney marrow. Because Gata2b could affect both transcription and chromatin accessibility during lineage differentiation, this was assessed by single-cell (sc) RNA-seq and single-nucleus (sn) ATAC-seq. Sn-ATAC-seq showed that the co-accessibility between the transcription start site (TSS) and a -3.5-4.1 kb putative enhancer was more robust in gata2b +/- zebrafish HSPCs compared to wild type, increasing gata2b expression and resulting in higher genome-wide Gata2b motif use in HSPCs. As a result of increased accessibility of the gata2b locus, gata2b +/- chromatin was also more accessible during lineage differentiation. scRNA-seq data revealed myeloid differentiation defects, that is, impaired cell cycle progression, reduced expression of cebpa and cebpb and increased signatures of ribosome biogenesis. These data also revealed a differentiation delay in erythroid progenitors, aberrant proliferative signatures and down-regulation of Gata1a, a master regulator of erythropoiesis, which worsened with age. These findings suggest that cell-intrinsic compensatory mechanisms, needed to obtain normal levels of Gata2b in heterozygous HSPCs to maintain their integrity, result in aberrant lineage differentiation, thereby representing a critical step in the predisposition to MDS., (© 2024 The Author(s). British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

Objectives: Diagnostic tools for voice disorders are lacking for primary care physicians. Artificial intelligence (AI) tools may add to the armamentarium for physicians, decreasing the time to diagnosis and limiting the burden of dysphonia., Methods: Voice recordings of patients were collected from 2019 to 2021 using smartphones. The Saarbruecken dataset was included for comparison. Audio files were converted to mel-spectrograms using TensorFlow. Diagnostic categories were created to group pathology, including neurological and muscular disorders, inflammatory, mass lesions, and normal. The samples were further separated into sustained/a/and the rainbow passage., Results: Two hundred three prospective samples and 1131 samples were used from the Saarbruecken database. The AI detected abnormal pathology with an F1-score of 98%. The artificial neural network (ANN) differentiated key pathologies, including unilateral paralysis, laryngitis, adductor spasmodic dysphonia (ADSD), mass lesions, and normal samples with 39%-87% F-1 scores. The Calgary database models had higher F-1 scores in a head-to-head comparison to the Saarbruecken and combined datasets (87% vs. 58% and 50%). The AI outperformed otolaryngologists using a standardized test set of recordings (83% compared to 55% ± 15%)., Conclusion: An AI tool was created to differentiate pathology by individual or categorical diagnosis with high evaluation metrics. Prospective data should be collected in a controlled fashion to reduce intrinsic variability between recordings. Multi-center data collaborations are imperative to increase the prediction capability of AI tools for detecting vocal cord pathology. We provide proof-of-concept for an AI tool to assist primary care physicians in managing dysphonic patients., Level of Evidence: 3 Laryngoscope, 133:1952-1960, 2023., (© 2022 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives/hypothesis: Cricotracheal resection (CTR) is an effective treatment for refractory idiopathic subglottic stenosis (iSGS) but is associated with persistent dysphonia. Outcomes were measured longitudinally to characterize how patients' voices and self-perceived voice handicaps changed after CTR., Study Design: Retrospective case-series., Methods: We conducted a retrospective cohort study of patients with refractory iSGS treated by CTR from 2006 to 2017. Voice Handicap Index (VHI), Consensus Auditory-Perceptual Evaluation of Voice (CAPE-V), and acoustic analysis were prospectively collected preoperatively and postoperatively at 1, 3, 6, 12, and 24-month intervals. A linear mixed model was used to evaluate temporal change., Results: Thirty-three patients (97% female) were included. VHI scores increased significantly from baseline preoperative score (27.2 ± 22.7) to a mean value of 44.3 ± 25.6 (P < .001) 1-month postoperatively but decreased below preoperative scores after 2 years (18.8 ± 11.9, P = .795). Mean fundamental frequency (F0) values in speech decreased significantly from 192.0 ± 24.9 Hz preoperatively to 167.1 ± 19.8 Hz at a 2-year follow-up (P = .002), with a nadir value at 1-month postoperatively (148.4 ± 20.5, P < .001). CAPE-V scores increased significantly from preoperative to 1-month postoperative (3.0 ± 2.3 vs. 21.9 ± 17.3, P < .001) but returned toward baseline values at 24 months after CTR (6.9 ± 4.8, P = .027). CAPE-V measurements postoperatively were correlated with VHI and F0 (Pearson coefficient = 0.54 (VHI), -0.46 (F0), P < .001)., Conclusions: Following CTR, mean F0 values were significantly and consistently lower but did increase over time, correlating with patients' improving VHI and CAPE-V scores. VHI values indicate that patient's perception of their voice is not significantly impacted in long term. These results provide a framework to counsel patients about long term voice expectations., Level of Evidence: 4 Laryngoscope, 132:1054-1060, 2022., (© 2021 The American Laryngological, Rhinological and Otological Society, Inc.)

The acoustic startle reflex is strongly inhibited by a moderate-intensity acoustic stimulus that precedes the startling stimulus by roughly 10-1000 ms (prepulse inhibition, PPI). At long interstimulus intervals (ISIs) of 100-1000 ms, PPI in rats is reduced by the muscarinic receptor antagonist scopolamine. Here, we studied the role of GABA receptors in PPI at full ISI ranges in both mice and rats. In B6 mice, PPI begins and ends at shorter ISIs (4 and 1000 ms, respectively) than in Wistar rats (8 and 5000 ms). The GABA(A) antagonist bicuculline (1 mg/kg i.p.) reduced PPI at ISIs near the peak of PPI in both rats and mice. The GABA(B) antagonist phaclofen (10 or 30 mg/kg i.p. in rats or mice, respectively) reduced PPI only at long ISIs, similar to the effects of the muscarinic antagonist scopolamine (1 mg/kg i.p.). The effects of phaclofen and scopolamine were additive in rats, suggesting independent effects of GABA(B) and muscarinic receptors. Patch-clamp recordings of startle-mediating PnC (nucleus reticularis pontis caudalis) giant neurons in rat slices show that EPSCs evoked by either trigeminal or auditory fiber stimulation were inhibited by the GABA(A/C) agonist muscimol or the GABA(B) agonist baclofen via postsynaptic mechanisms. Hyperpolarization of PnC neurons by muscimol was reversed with bicuculline, indicating that postsynaptic GABA(A) receptors strongly inhibit PnC giant neurons needed for startle. Therefore, GABA receptors on PnC giant neurons mediate a substantial part of PPI, with GABA(A) receptors contributing at the peak of PPI, and GABA(B) receptors adding to muscarinic effects on PPI at long ISIs.

Giant neurones in the caudal pontine reticular nucleus (PnC) play a crucial role in mediating the mammalian startle response. They receive input from cochlear, trigeminal and vestibular nuclei and project directly to motoneurones. Furthermore, they integrate modulatory input from different brain regions either enhancing or inhibiting startle responses. One prominent startle modulation is prepulse inhibition where a non-startling stimulus presented prior to the startle stimulus inhibits a subsequent startle response. Several behavioural studies have indicated that this inhibition is mediated by muscarinic receptors at the level of the PnC. Here, we performed whole-cell patch-clamp recordings from PnC giant neurones in acute rat brain slices in order to examine muscarinic inhibition. We stimulated afferent trigeminal and auditory fibres and applied muscarinic agonists and antagonists in order to investigate their effect on excitatory postsynaptic current amplitudes, paired-pulse ratio and passive membrane properties of PnC giant neurones. The cholinergic agonist carbachol and the muscarinic agonist oxotremorine significantly reduced excitatory postsynaptic current amplitudes and increased the paired-pulse ratio. Carbachol additionally reduced the membrane resistance of postsynaptic PnC giant neurones. The subtype-specific antagonists AF-DX116 (M2 preferring) and tropicamide (M4 preferring) antagonized the oxotremorine effect indicating that M4 and possibly M2 receptor subtypes are involved in this inhibition. The G-protein-activated inward rectifying potassium channel blocker tertiapin-Q had no effect on oxotremorine-induced inhibition of giant neurones. Our results show a mainly presynaptically mediated strong inhibition of PnC giant neurones by activation of M4 and possibly M2 receptors that presumably contribute to prepulse inhibition.

The cytotoxic action of various single doses of MNU and ENU on developing neural and extraneural tissues was studied at different stages of development. Examination revealed lethal damage. (L.I.) and mitotic inhibition (M.I.), confined to proliferating cells only, and caused by the number of alkyl groups administered. In studying the duration of M.I. a difference was found in duration of the cell cycle arrest after MNU or ENU. The arrest lasted longer for MNU than for ENU, and the neural tissues turned out to be more sensitive than the extraneural ones. Moreover, among the reappearing mitotic figures abnormal ones were noticed frequently. After pulse-labeling with thymidine this arrest could be traced to take place in or before entering the S-phase. During the period of this arrest a low, but specific, activity was found that might point to the existence of repair-processes in vivo. Finally, we directly demonstrated alkylations in tissue-sections by the use of (14C-methyl)-MNU. High radioactivity was found with a random distribution over the various tissues, cell types and even cellular compartments. Therefore--in contrast with the cytotoxic effects--alkylation seems to occur in all cell types. In conclusion, it seems justified to consider the matrices of proliferating cells in the central nervous system as the target tissue-areas for the carcinogenic action of both MNU and ENU. Re-entrance of these damaged cells into their cycle prior to the elimination of altered bases from DNA might be of great importance for the problem of oncogenesis.

Single injections on ENU to WAG-rats were given in the perinatal period and repeated injections of MNU to adult WAG-rats. In the tables illustrating the various experiments, the occurrence of tumors is given for each animal; the tumors are classified according to their sites. For the brain tumors a subdivision is made between those macroscopically visible and those discovered only under microscopy. It is noteworthy that the ratio between neural and extraneural tumors in the perinatally exposed animals is rather constant (about 90 and 10 per cent, respectively). In the experiments on young adult rats neural tumors still predominate, but estraneural ones rise to about 40 per cent. The incidence of neural tumors is impressively high in perinatal induction experiments (greater than 95 per cent). Almost all CNS tumors showed the characteristics of oligodendrogliomas; highly differentiated in the smaller tumors and more anaplastic with regressive changes in the larger ones.