Epistemic modality of the multiple compound-complex sentences

The present paper focuses on the problem of distinguishing between the root and epistemic modal meanings expressed by the certain modal verbs in the multiple compound-complex sentences in modern English. Peculiarities of modal meanings are observed, details of implementation of modality singled outye

Behavioral, electrophysiological and histopathological consequences of systemic manganese administration in MEMRI

Manganese (Mn2+)-enhanced magnetic resonance imaging (MEMRI) offers the possibility to generate longitudinal maps of brain activity in unrestrained and behaving animals. However, Mn2+ is a metabolic toxin and a competitive inhibitor for Ca2+, and therefore, a yet unsolved question in MEMRI studies is whether the concentrations of metal ion used may alter brain physiology. In the present work we have investigated the behavioral, electrophysiological and histopathological consequences of MnCl2 administration at concentrations and dosage protocols regularly used in MEMRI. Three groups of animals were sc injected with saline, 0.1 and 0.5 mmol/kg MnCl2, respectively. In vivo electrophysiological recordings in the hippocampal formation revealed a mild but detectable decrease in both excitatory postsynaptic potentials (EPSP) and population spike (PS) amplitude under the highest MnCl2 dose. The EPSP to PS ratio was preserved at control levels, indicating that neuronal excitability was not affected. Experiments of pair pulse facilitation demonstrated a dose dependent increase in the potentiation of the second pulse, suggesting presynaptic Ca2+ competition as the mechanism for the decreased neuronal response. Tetanization of the perforant path induced a long-term potentiation of synaptic transmission that was comparable in all groups, regardless of treatment. Accordingly, the choice accuracy tested on a hippocampal-dependent learning task was not affected. However, the response latency in the same task was largely increased in the group receiving 0.5 mmol/kg of MnCl2. Immunohistological examination of the hippocampus at the end of the experiments revealed no sign of neuronal toxicity or glial reaction. Although we show that MEMRI at 0.1 mmol/Kg MnCl2 may be safely applied to the study of cognitive networks, a detailed assessment of toxicity is strongly recommended for each particular study and Mn2+ administration protocol

Synchronous spiking associated with prefrontal high y oscillations evokes a 5-Hz rhythmic modulation of spiking in locus coeruleus

The brainstem noradrenergic locus coeruleus (LC) is reciprocally connected with the prefrontal cortex (PFC). Coupling between LC spiking and the depolarizing phase of slow (1?2 Hz) waves in PFC field potentials during sleep and anesthesia suggests that LC drives cortical state transition. Reciprocal LC-PFC connectivity should also allow interactions in the opposing (top-down) direction, but prior work has only studied prefrontal control over LC activity using electrical or optogenetic stimulation. Here, we describe the physiological characteristics of spontaneously occurring top-down LC-PFC interactions. We recorded LC multiunit activity (MUA) simultaneously with PFC single-unit and local field potential (LFP) activity in urethane-anesthetized rats. We observed cross-regional coupling between the phase of 5-Hz oscillations in LC-MUA and the power of PFC LFP 60?200 Hz high y (hy). Transient increases in PFC hy power preceded peaks in the 5-Hz LC-MUA oscillation. Analysis of cross-regional transfer entropy demonstrated that the PFC hy transients were predictive of a transient increase in LC-MUA. An -29 ms delay between these signals was consistent with the conduction velocity from the PFC to the LC. Finally, we showed that PFC hy transients are associated with synchronized spiking of a subset (27%) of PFC single units. Our data suggest that PFC hy transients may indicate the timing of the top-down excitatory input to LC, at least under conditions when LC neuronal population activity fluctuates rhythmically at 5 Hz. Synchronized PFC neuronal spiking that occurs during hy transients may provide a previously unknown mode of top-down control over the LC. NEW & NOTEWORTHY The prefrontal cortex (PFC) is thought to control activity in the noradrenergic locus coeruleus (LC). Prior anatomical and prefrontal stimulation studies demonstrated the potential for PFC-LC interactions; however, it is unknown what types of PFC activity affect the LC. Here, we show that transient increases in PFC high y power and associated changes in PFC unit-pair synchrony are a potential sign of top-down control over the LC.Peer reviewe

A low power prescaler, phase frequency detector, and charge pump for a 12 ghz frequency synthesizer

A low power implementation of a CMOS frequency synthesizer at 12 GHz is an important step to improve the efficiency of a wireless transceiver in this frequency band. Since synthesizers are often employed as reference frequency sources such as local oscillators for up or down-conversion in communications system, their design is especially important for high performance transceiver applications. CMOS PLLs operating at high frequencies consume large amounts of power for proper operation, making power efficiency a top priority in transciever implementation. In response, this thesis presents a low power phase and frequency detector with True Single Phase Clocking by employing the .18μ TSMC process with a 1.8 V supply voltage. A conventional but extremely power efficient nano-watt charge pump is also implemented for additional power savings. Furthermore, a state of the art 16/17 prescaler using Current Mode Logic (CML) D-Flip Flops, CMOS inverters, and transmission gates has been optimized for maximum power savings. The prescaler consists of a 4/5 synchronous core and a feedback loop which modulates the 4/5 core to produce a division ratio of 16/17. Instead of employing power hungry CML, the feedback circuit takes advantage of low power NOR and AND gates realized in Transmission Gate Logic (TGL) to reduce the power consumption. To the best of my knowledge, this technique has never been used in a high frequency prescaler before

Finite-element analysis of biomechanical simulation of three-dimensional model of the "bone - dental implant - supraconstruction"

В даній роботі на сучасному рівні комп’ютерного та програмного забезпечення проведено розрахунково-теоретичний аналіз сил, напружень та деформацій біомеханічної системи «кісткова тканина - дентальний імплантат - супраконструкція». Встановлено закономірності опороздатності кісткової тканини щелепи до функціональних навантажень дентальних імплантатів, що залежать від анатомічної будови альвеолярного відростку та будови оклюзійної поверхні супраконструкцій. Розрахована площа контакту поверхні дентальних імплантів з кортикальною та губчастою кістковими тканинами різного об’єму, які визначають параметри опороздатності до деформацій у випадку складного виду напружено-деформованого стану кістки щелепи сполученої з імплантом.In this paper, up to date computer hardware and software was held by calculation and theoretical analysis of the forces of the biomechanical stresses and strains of the "bone - dental implant - supraconstruction". The laws of the bearing capacity of the jaw bone to functional load of dental implants were investigated, depending on the anatomy of the alveolar process and the structure of the occlusal surface supraconstructions. There were calculated the surface area of contact of dental implants with cortical and trabecular bone tissue of different volume that determines the carrying capacity to deformations in the case of complicated form of the stress-strain state of the jaw bone in connection to implant. Purpose Perform incremental numerical and theoretical study concernig study of capacity and mechanical aspects of distribution and stress concentration of the deformation of bone biomechanical system "bone - dental implants - supraconstruction" (KDIS) rights under physiological norm biological tissue based on advanced techniques using bioengineering analysis CAD / CAE technologies. Findings. Increase capacity of CT associated with the approach vector functional load on the surface occlusion crowns dental implant to implant symmetriyi axial lines and reduce of capacity observed in bias surface centrifugal force loads and an increase in the angle of the main vector of force load.В данной работе на современном уровне компьютерного и программного обеспечения проведено расчетно-теоретический анализ сил, напряжений и деформаций биомеханической системы «костная ткань - дентальный имплантат - супраконструкция». Установлены закономерности для несущей способности костных тканей челюсти к функциональным нагрузкам дентальных имплантатов, зависящие от анатомического строения альвеолярного отростка и строения окклюзионной поверхности супраконструкции. Рассчитана площадь контакта поверхности дентальных имплантатов с кортикальной и губчатой костной тканью, которая определяет параметры несущей способности кости к деформациям в случае сложного вида напряженно-деформированного состояния кости челюсти соединенной с имплантатом

Neuroimaging reveals functionally distinct neuronal networks associated with high-level alcohol consumption in two genetic rat models

Human imaging data suggest that the motivational processes associated with alcohol reward are reflected in the patterns of neural activation after alcohol or alcohol-related cues. In animal models of alcohol drinking, however, the changes in brain activation during voluntary alcohol ingestion are poorly known. In order to improve the translational utility of animal models, we examined alcohol-induced functional brain activation in Alko Alcohol (AA) and Marchigian-Sardinian alcohol-preferring (msP) rats that drink voluntarily high levels of alcohol, but exhibit widely different neurochemical and behavioral traits cosegregated with alcohol preference. Brain imaging was performed using manganese-enhanced MRI (MEMRI), which is based on accumulation of Mn2+ ions in activated neurons, allowing the identification of functional neuronal networks recruited during specific behaviors in awake animals during a subsequent imaging session under anesthesia. MEMRI was performed following 4 weeks of voluntary alcohol drinking, using water drinking as the control. Despite similar levels of alcohol drinking, strikingly different alcohol-induced neuronal activity patterns were observed in AA and msP rats. Overall, functional activation in the AA rats was more widespread, involving large cortical areas and subcortical structures, such as the bed nucleus of the stria terminalis, preoptic area, hypothalamus, periaqueductal grey, and substantia nigra. In the msP rats, however, alcohol-related activation was largely confined to prefrontal cortical regions and insular cortex, and olfactory areas. Overlapping areas of activation found in both rat lines included the nucleus accumbens, prelimbic, orbital, and insular cortex. In conclusion, our data reveal strikingly different brain circuits associated with alcohol drinking in two genetically different rat lines and suggest innately different motivational and behavioral processes driving alcohol drinking. These findings have important implications for the use of these lines in translational alcohol research.Peer reviewe

The Sleeping Brain's Influence on Verbal Memory: Boosting Resistance to Interference

Memories evolve. After learning something new, the brain initiates a complex set of post-learning processing that facilitates recall (i.e., consolidation). Evidence points to sleep as one of the determinants of that change. But whenever a behavioral study of episodic memory shows a benefit of sleep, critics assert that sleep only leads to a temporary shelter from the damaging effects of interference that would otherwise accrue during wakefulness. To evaluate the potentially active role of sleep for verbal memory, we compared memory recall after sleep, with and without interference before testing. We demonstrated that recall performance for verbal memory was greater after sleep than after wakefulness. And when using interference testing, that difference was even more pronounced. By introducing interference after sleep, this study confirms an experimental paradigm that demonstrates the active role of sleep in consolidating memory, and unmasks the large magnitude of that benefit

To Sleep, to Strive, or Both: How Best to Optimize Memory

While numerous studies have shown that a night of sleep profits memory relative to wake, we still have little understanding about what factors mediate this effect of sleep. A clear understanding of the dynamics of this effect of sleep beyond the initial night of sleep is also lacking. Here, we examined the effect of extrinsic rewards on sleep-dependent declarative memory processing across 12 and 24 hr training-retest intervals. Subjects were either paid based on their performance at retest ($1 for each correct answer), or received a flat fee for participation. After a 12 hr interval we observed pronounced benefits of both sleep and reward on memory. Over an extended 24 hr interval we found 1) that an initial night of sleep partially protects memories from subsequent deterioration during wake, and 2) that sleep blocks further deterioration, and may even have a restorative effect on memory, when it follows a full day of wake. Interestingly, the benefit imparted to rewarded (relative to unrewarded) stimuli was equal for sleep and wake subjects, suggesting that the sleeping brain may not differentially process rewarded information, relative to wake. However, looking at the overall impact of sleep relative to reward in this protocol, it was apparent that sleep both imparted a stronger mnemonic boost than reward, and provided a benefit to memory regardless of whether it occurred in the first or the second 12 hrs following task training

Priorities for research on neuromodulatory subcortical systems in Alzheimer's disease: Position paper from the NSS PIA of ISTAART

The neuromodulatory subcortical system (NSS) nuclei are critical hubs for survival, hedonic tone, and homeostasis. Tau-associated NSS degeneration occurs early in Alzheimer's disease (AD) pathogenesis, long before the emergence of pathognomonic memory dysfunction and cortical lesions. Accumulating evidence supports the role of NSS dysfunction and degeneration in the behavioral and neuropsychiatric manifestations featured early in AD. Experimental studies even suggest that AD-associated NSS degeneration drives brain neuroinflammatory status and contributes to disease progression, including the exacerbation of cortical lesions. Given the important pathophysiologic and etiologic roles that involve the NSS in early AD stages, there is an urgent need to expand our understanding of the mechanisms underlying NSS vulnerability and more precisely detail the clinical progression of NSS changes in AD. Here, the NSS Professional Interest Area of the International Society to Advance Alzheimer's Research and Treatment highlights knowledge gaps about NSS within AD and provides recommendations for priorities specific to clinical research, biomarker development, modeling, and intervention. HIGHLIGHTS: Neuromodulatory nuclei degenerate in early Alzheimer's disease pathological stages. Alzheimer's pathophysiology is exacerbated by neuromodulatory nuclei degeneration. Neuromodulatory nuclei degeneration drives neuropsychiatric symptoms in dementia. Biomarkers of neuromodulatory integrity would be value-creating for dementia care. Neuromodulatory nuclei present strategic prospects for disease-modifying therapies

Odor Fear Conditioning Modifies Piriform Cortex Local Field Potentials Both during Conditioning and during Post-Conditioning Sleep

BACKGROUND: Sleep plays an active role in memory consolidation. Sleep structure (REM/Slow wave activity [SWS]) can be modified after learning, and in some cortical circuits, sleep is associated with replay of the learned experience. While the majority of this work has focused on neocortical and hippocampal circuits, the olfactory system may offer unique advantages as a model system for exploring sleep and memory, given the short, non-thalamic pathway from nose to primary olfactory (piriform cortex), and rapid cortex-dependent odor learning. METHODOLOGY/PRINCIPAL FINDINGS: We examined piriform cortical odor responses using local field potentials (LFPs) from freely behaving Long-Evans hooded rats over the sleep-wake cycle, and the neuronal modifications that occurred within the piriform cortex both during and after odor-fear conditioning. We also recorded LFPs from naïve animals to characterize sleep activity in the piriform cortex and to analyze transient odor-evoked cortical responses during different sleep stages. Naïve rats in their home cages spent 40% of their time in SWS, during which the piriform cortex was significantly hypo-responsive to odor stimulation compared to awake and REM sleep states. Rats trained in the paired odor-shock conditioning paradigm developed enhanced conditioned odor evoked gamma frequency activity in the piriform cortex over the course of training compared to pseudo-conditioned rats. Furthermore, conditioned rats spent significantly more time in SWS immediately post-training both compared to pre-training days and compared to pseudo-conditioned rats. The increase in SWS immediately after training significantly correlated with the duration of odor-evoked freezing the following day. CONCLUSIONS/SIGNIFICANCE: The rat piriform cortex is hypo-responsive to odors during SWS which accounts for nearly 40% of each 24 hour period. The duration of slow-wave activity in the piriform cortex is enhanced immediately post-conditioning, and this increase is significantly correlated with subsequent memory performance. Together, these results suggest the piriform cortex may go offline during SWS to facilitate consolidation of learned odors with reduced external interference